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Sample records for zip8 hco3 dependent symporter

  1. ZIP8 zinc transporter: indispensable role for both multiple-organ organogenesis and hematopoiesis in utero.

    Directory of Open Access Journals (Sweden)

    Marina Gálvez-Peralta

    Full Text Available Previously this laboratory characterized Slc39a8-encoded ZIP8 as a Zn(2+/(HCO(3(-(2 symporter; yet, the overall physiological importance of ZIP8 at the whole-organism level remains unclear. Herein we describe the phenotype of the hypomorphic Slc39a8(neo/neo mouse which has retained the neomycin-resistance gene in intron 3, hence causing significantly decreased ZIP8 mRNA and protein levels in embryo, fetus, placenta, yolk sac, and several tissues of neonates. The Slc39a8(neo allele is associated with diminished zinc and iron uptake in mouse fetal fibroblast and liver-derived cultures; consequently, Slc39a8(neo/neo newborns exhibit diminished zinc and iron levels in several tissues. Slc39a8(neo/neo homozygotes from gestational day(GD-11.5 onward are pale, growth-stunted, and die between GD18.5 and 48 h postnatally. Defects include: severely hypoplastic spleen; hypoplasia of liver, kidney, lung, and lower limbs. Histologically, Slc39a8(neo/neo neonates show decreased numbers of hematopoietic islands in yolk sac and liver. Low hemoglobin, hematocrit, red cell count, serum iron, and total iron-binding capacity confirmed severe anemia. Flow cytometry of fetal liver cells revealed the erythroid series strikingly affected in the hypomorph. Zinc-dependent 5-aminolevulinic acid dehydratase, required for heme synthesis, was not different between Slc39a8(+/+ and Slc39a8(neo/neo offspring. To demonstrate further that the mouse phenotype is due to ZIP8 deficiency, we bred Slc39a8(+/neo with BAC-transgenic BTZIP8-3 line (carrying three extra copies of the Slc39a8 allele; this cross generated viable Slc39a8(neo/neo_BTZIP8-3(+/+ pups showing none of the above-mentioned congenital defects-proving Slc39a8(neo/neo causes the described phenotype. Our study demonstrates that ZIP8-mediated zinc transport plays an unappreciated critical role during in utero and neonatal growth, organ morphogenesis, and hematopoiesis.

  2. Cl--HCO-3 antiport in rat lacrimal gland

    International Nuclear Information System (INIS)

    Lambert, R.W.; Bradley, M.E.; Mircheff, A.K.

    1988-01-01

    With the use of analytical subcellular fractionation and tracer uptake methods the authors have demonstrated the presence of a Cl - -HCO - 3 antiport mechanism in the rat exorbital lacrimal gland. They find that outwardly directed gradients of HCO - 3 and of 35 Cl - accelerated the flux of 36 Cl - into isolated membrane vesicles. Because vesicle membrane potentials were clamped to 0 mV with K + -valinomycin, the observed anion gradient-dependent acceleration of Cl - influx could not be attributed to conductive fluxes. The antiporter had an apparent K 0.5 for Cl - between 6 and 10 mM. It was sensitive to the stilbene derivatives 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). It was also sensitive to the loop diuretic furosemide, which has frequently been used in tests for NaKCl 2 symporter activity. Other anions inhibited anion gradient-driven Cl - influx in the sequence SCN - > NO - 3 > Cl - HCO - 3 > SO 2- 4 . The density distribution of Cl - -HCO - 3 antiport activity indicated that ∼80% of the transporter was associated with intracellular membranes, suggesting the presence of cytoplasmic pools of functional antiporters. Because several studies have already shown the presence of Na + -H + antiporter activity in lacrimal acinar cell basolateral membranes, a cellular model for lacrimal acinar electrolyte secretion is proposed in which a parallel array of Cl - -HCO - 3 and Na + -H + antiporters mediates the Na + -dependent accumulation of Cl - against its electrochemical potential gradient

  3. Oncogenic p95HER2 regulates Na+-HCO3- cotransporter NBCn1 mRNA stability in breast cancer cells via 3'UTR-dependent processes.

    Science.gov (United States)

    Gorbatenko, Andrej; Olesen, Christina W; Loebl, Nathalie; Sigurdsson, Haraldur H; Bianchi, Carolina; Pedraz-Cuesta, Elena; Christiansen, Jan; Pedersen, Stine Falsig

    2016-11-01

    The Na + -HCO 3 - cotransporter NBCn1 (SLC4A7) is up-regulated in breast cancer, important for tumor growth, and a single nucleotide polymorphism (SNP), rs4973768, in its 3' untranslated region (3'UTR) correlates with increased breast cancer risk. We previously demonstrated that NBCn1 expression and promoter activity are strongly increased in breast cancer cells expressing a constitutively active oncogenic human epidermal growth factor receptor 2 (HER2) (p95HER2). Here, we address the roles of p95HER2 in regulating NBCn1 expression via post-transcriptional mechanisms. p95HER2 expression in MCF-7 cells reduced the rate of NBCn1 mRNA degradation. The NBCn1 3'UTR down-regulated luciferase reporter expression in control cells, and this was reversed by p95HER2, suggesting that p95HER2 counteracts 3'UTR-mediated suppression of NBCn1 expression. Truncation analyses identified three NBCn1 3'UTR regions of regulatory importance. Mutation of putative miRNA-binding sites (miR-374a/b, miR-200b/c, miR-29a/b/c, miR-488) in these regions did not have significant impact on 3'UTR activity. The NBCn1 3'UTR interacted directly with the RNA-binding protein human antigen R (HuR), and HuR knockdown reduced NBCn1 expression. Conversely, ablation of a distal AU-rich element increased 3'UTR-driven reporter activity, suggesting complex regulatory roles of these sites. The cancer-associated SNP variant decreased reporter expression in T-47D breast cancer cells, yet not in MCF-7, MDA-MB-231 and SK-BR-3 cells, arguing against a general role in regulating NBCn1 expression. Finally, p95HER2 expression increased total and plasma membrane NBCn1 protein levels and decreased the rate of NBCn1 protein degradation. Collectively, this is the first work to demonstrate 3'UTR-mediated NBCn1 regulation, shows that p95HER2 regulates NBCn1 expression at multiple levels, and substantiates the central position of p95HER2-NBCn1 signaling in breast cancer. © 2016 The Author(s); published by Portland Press

  4. Proton-stimulated Cl-HCO3 antiport by basolateral membrane vesicles of lobster hepatopancreas

    International Nuclear Information System (INIS)

    Ahearn, G.A.; Grover, M.L.; Tsuji, R.T.; Clay, L.P.

    1987-01-01

    Purified epithelial basolateral membrane vesicles were prepared from lobster hepatopancreas by sorbitol gradient centrifugation. Na+-K+-adenosinetriphosphatase, alkaline phosphatase, and cytochrome-c oxidase enzyme activities in the final membrane preparation were enriched 9.6-, 1.4-, and 0.4-fold, respectively, compared with their activities in the original tissue homogenate. Vesicle osmotic reactivity was demonstrated using 60-min equilibrium 36 Cl uptake experiments at a variety of transmembrane osmotic gradients. 36 Cl uptake into vesicles preloaded with HCO 3 was significantly greater than into vesicles lacking HCO 3 . This exchange process was stimulated by a transmembrane proton gradient (internal pH greater than external pH). Proton-gradient-dependent Cl-HCO 3 exchange was potential sensitive and stimulated by an electrically negative vesicle interior. 36 Cl influx (4-s exposures) into HCO 3 -loaded vesicles occurred by the combination of 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid sensitive, carrier-mediated transfer and apparent diffusion. 36 Cl influx was a hyperbolic function of both internal [HCO 3 ] and internal [Cl]. The two internal anions displayed a 100-fold difference in apparent affinity constants with HCO 3 being strongly preferred. 36 Cl influx was stimulated more by preloaded monovalent than by divalent anions. Na was an inhibitor of proton-dependent anion antiport, whereas K had no effect. A model for HCl-HCO 3 antiport is suggested that employs combined transmembrane concentration gradients of Cl and HCO 3 to power anion exchange and transfer protons against a concentration gradient

  5. Secretin stimulates HCO3(-) and acetate efflux but not Na+/HCO3(-) uptake in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Novak, I; Christoffersen, B C

    2001-01-01

    to be important in HCO3(-) -transporting epithelia. pHi was measured with BCECF in freshly isolated intralobular ducts. A reduction in extracellular Na+ concentration or application of HOE 694 (1 microM) decreased pHi by 0.1 to 0.6 pH units, demonstrating Na+/H+ exchanger activity. A reduction in extracellular Cl......- concentration or addition of H2DIDS (10 microM) increased pHi by 0.1 to 0.5 pH units, demonstrating Cl-/ HCO(3)- (OH ) exchanger activity. In experimental acidosis, extracellular HCO3(-)/CO2 buffer did not increase the rate of pHi recovery, indicating that provision of HCO3(-) by the Na+/HCO3(-) cotransporter...... was not apparent. Most importantly, Na+/HCO3(-) cotransport was not stimulated by secretin (1 nM). In contrast, in experimental alkalosis the pHi recovery was increased in HCO3(-)/CO2 buffer, possibly due to Na+/HCO3(-) cotransport in the efflux mode. Secretin (1 nM) and carbachol (1 microM) stimulated HCO3...

  6. Substrate Specificity of Na+,Cl-(HCO3-)-ATPase.

    Science.gov (United States)

    Yurkiv, V A; Melikhov, V I; Shubin, V S

    2016-09-01

    We studied substrate specificity of Na + ,Cl - (HCO 3 - )-ATPase. In most cases, replacement of ATP for other phosphate-containing substances resulted in not only pronounced suppression of phosphohydrolase reactions, but also dramatic changes of their responsiveness to the stimulating effect of monovalent ions. The data showed that Na + ,Cl - (HCO 3 - )-ATPase is a highly specific enzyme for ATP.

  7. Ursodeoxycholic acid choleresis: Relationship to biliary HCO-3 and effects of Na+-H+ exchange inhibitors

    International Nuclear Information System (INIS)

    Renner, E.L.; Lake, J.R.; Cragoe, E.J. Jr.; van Dyke, R.W.; Scharschmidt, B.F.

    1988-01-01

    The authors have recently shown that substitution of Li + for perfusate Na + eliminates the HCO 3 - -rich choleresis produced by ursodeoxycholic acid (UDCA) in isolated perfused rat liver and that the increase in bile flow produced by both UDCA and taurocholic acid is partially inhibited by 1 mM amiloride. Although these findings are consistent with a role for Na + -H + exchange in the choleresis produced by these bile acids, both Li + substitution and amiloride affect other cellular processes, including Na + -K + -ATPase activity. They have now further explored both the relationship between UDCA-stimulated bile flow and biliary HCO 3 - secretion and the possible role of Na + -H + exchange in this process by comparing the effects of amiloride with two of its more potent and presumably more specific analogues, 5-(N,N-dimethyl)amiloride hydrochloride (DMA) and 5-(N-ethyl-N-isopropyl)amiloride (EIA). None of the inhibitors significantly altered biliary UDCA output or the relationship between UDCA-induced bile flow and either biliary [HCO 3 - ] or biliary HCO 3- output. Effects of these inhibitors did not appear attributable either to nonspecific toxicity, as reflected by hepatic release of lactate dehydrogenase or K + , or to inhibition of hepatic Na + -K + -ATPase, measured as Na + -dependent uptake of 86 Rb. These findings indicate that UDCA-induced but not basal bile formation is closely coupled to biliary HCO 3 - concentration and output, and they provide additional evidence that UDCA choleresis requires an intact Na + -H + exchange mechanism

  8. HCO3(-)-coupled Na+ influx is a major determinant of Na+ turnover and Na+/K+ pump activity in rat hepatocytes

    International Nuclear Information System (INIS)

    Fitz, J.G.; Lidofsky, S.D.; Weisiger, R.A.; Xie, M.H.; Cochran, M.; Grotmol, T.; Scharschmidt, B.F.

    1991-01-01

    Recent studies in hepatocytes indicate that Na(+)-coupled HCO3- transport contributes importantly to regulation of intracellular pH and membrane HCO3- transport. However, the direction of net coupled Na+ and HCO3- movement and the effect of HCO3- on Na+ turnover and Na+/K+ pump activity are not known. In these studies, the effect of HCO3- on Na+ influx and turnover were measured in primary rat hepatocyte cultures with 22Na+, and [Na+]i was measured in single hepatocytes using the Na(+)-sensitive fluorochrome SBFI. Na+/K+ pump activity was measured in intact perfused rat liver and hepatocyte monolayers as Na(+)-dependent or ouabain-suppressible 86Rb uptake, and was measured in single hepatocytes as the effect of transient pump inhibition by removal of extracellular K+ on membrane potential difference (PD) and [Na+]i. In hepatocyte monolayers, HCO3- increased 22Na+ entry and turnover rates by 50-65%, without measurably altering 22Na+ pool size or cell volume, and HCO3- also increased Na+/K+ pump activity by 70%. In single cells, exposure to HCO3- produced an abrupt and sustained rise in [Na+]i from approximately 8 to 12 mM. Na+/K+ pump activity assessed in single cells by PD excursions during transient K+ removal increased congruent to 2.5-fold in the presence of HCO3-, and the rise in [Na+]i produced by inhibition of the Na+/K+ pump was similarly increased congruent to 2.5-fold in the presence of HCO3-. In intact perfused rat liver, HCO3- increased both Na+/K+ pump activity and O2 consumption. These findings indicate that, in hepatocytes, net coupled Na+ and HCO3- movement is inward and represents a major determinant of Na+ influx and Na+/K+ pump activity. About half of hepatic Na+/K+ pump activity appears dedicated to recycling Na+ entering in conjunction with HCO3- to maintain [Na+]i within the physiologic range

  9. Characterization of Na+-linked and Na+-independent Cl-/HCO3- exchange systems in Chinese hamster lung fibroblasts

    International Nuclear Information System (INIS)

    Cassel, D.; Scharf, O.; Rotman, M.; Cragoe, E.J. Jr.; Katz, M.

    1988-01-01

    The PS120 variant of Chinese hamster lung fibroblasts which lacks Na + /H + exchange activity was used to investigate bicarbonate transport systems and their role in intracellular pH (pH/sub i/) regulation. When pH/sub i/ was decreased by acid load, bicarbonate caused pH/sub i/ increase and stimulated 36 Cl - efflux from the cells, both in a Na + -dependent manner. These results together with previous findings that bicarbonate stimulates 22 Na + uptake in PS120 cells demonstrate the presence of a Na + -linked Cl - /HCO 3 - exchange system. In cells with normal initial pH/sub i/, bicarbonate caused Na + -independent pH/sub i/ increase in Cl - -free solutions and stimulated Na + -independent 36 Cl - efflux, indicating that a Na + -independent Cl - /HCO 3 - exchanger is also present in the cell. Na + -linked and Na + -independent Cl - /HCO 3- exchange is apparently mediated by two distinct systems, since a [(tetrahydrofluorene-7-yl)oxy]acetic acid derivative selectively inhibits the Na + -independent exchanger. An additional distinctive features is a 10-fold lower affinity for chloride of the Na + -linked exchanger. The Na + -linked and Na + -independent Cl - /HCO 3 - exchange systems are likely to protect the cell from acid and alkaline load, respectively

  10. Essential role of the electroneutral Na+-HCO3- cotransporter NBCn1 in murine duodenal acid-base balance and colonic mucus layer build-up in vivo.

    Science.gov (United States)

    Singh, Anurag Kumar; Xia, Weiliang; Riederer, Brigitte; Juric, Marina; Li, Junhua; Zheng, Wen; Cinar, Ayhan; Xiao, Fang; Bachmann, Oliver; Song, Penghong; Praetorius, Jeppe; Aalkjaer, Christian; Seidler, Ursula

    2013-04-15

    Duodenal epithelial cells need efficient defence strategies during gastric acidification of the lumen, while colonic mucosa counteracts damage by pathogens by building up a bacteria-free adherent mucus layer. Transport of HCO3(-) is considered crucial for duodenal defence against acid as well as for mucus release and expansion, but the transport pathways involved are incompletely understood. This study investigated the significance of the electroneutral Na(+)-HCO3(-) cotransporter NBCn1 for duodenal defence against acid and colonic mucus release. NBCn1 was localized to the basolateral membrane of duodenal villous enterocytes and of colonic crypt cells, with predominant expression in goblet cells. Duodenal villous enterocyte intracellular pH was studied before and during a luminal acid load by two-photon microscopy in exteriorized, vascularly perfused, indicator (SNARF-1 AM)-loaded duodenum of isoflurane-anaesthetized, systemic acid-base-controlled mice. Acid-induced HCO3(-) secretion was measured in vivo by single-pass perfusion and pH-stat titration. After a luminal acid load, NBCn1-deficient duodenocytes were unable to recover rapidly from intracellular acidification and could not respond adequately with protective HCO3(-) secretion. In the colon, build-up of the mucus layer was delayed, and a decreased thickness of the adherent mucus layer was observed, suggesting that basolateral HCO3(-) uptake is essential for optimal release of mucus. The electroneutral Na(+)-HCO3(-) cotransporter NBCn1 displays a differential cellular distribution in the murine intestine and is essential for HCO3(-)-dependent mucosal protective functions, such as recovery of intracellular pH and HCO3(-) secretion in the duodenum and secretion of mucus in the colon.

  11. Effective identification of (NH4)2CO3 and NH4HCO3 concentrations in NaHCO3 regeneration process from desulfurized waste.

    Science.gov (United States)

    Govindan, Muthuraman; Karunakaran, Kannan; Nallasamy, Palanisami; Moon, Il Shik

    2015-01-01

    This work describes the quantitative analysis of (NH4)2CO3 and NH4HCO3 using a simple solution phase titration method. Back titration results at various (NH4)2CO3-NH4HCO3 ratios demonstrated that 6:4 ratio caused a 3% error in their differentiation, but very high errors were found at other ratios. A similar trend was observed for the double indicator method, especially when strong acid HCl was used as a titrant, where still less errors (2.5%) at a middle ratio of (NH4)2CO3-NH4HCO3 was found. Remaining ratios with low (NH4)2CO3 (2:8, 4:6) show high +ve error (found concentration is less) and high (NH4)2CO3 (7:3, 8:2, and 9:1) show high -ve error (found concentration is higher) and vice versa for NH4HCO3. In replacement titration using Na2SO4, at both higher end ratios of (NH4)2CO3-NH4HCO3 (2:8 and 9:1), both -ve and +ve errors were minimized to 75% by partial equilibrium arrest between (NH4)2CO3 and NH2COONH4, instead of more than 100% observed in back titration and only double indicator methods. In the presence of (NH4)2SO4 both -ve and +ve error% are completely reduced to 3±1 at ratios 2:8, 4:6, and 6:4 of (NH4)2CO3-NH4HCO3, which demonstrates that the equilibrium transformation between NH2COONH4 and (NH4)2CO3 is completely controlled. The titration conducted at lower temperature (5 °C) in the presence of (NH4)2SO4 at higher ratios of (NH4)2CO3-NH4HCO3 (7:3, 8:2,and 9:1) shows complete minimization of both -ve and +ve errors to 2±1%, which explains the complete arresting of equilibrium transformation. Finally, the developed method shows 2±1% error in differentiation of CO3(2-) and HCO3(-) in the regeneration process of NaHCO3 from crude desulfurized sample. The developed method is more promising to differentiate CO3(2-) and HCO3(-) in industrial applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Stimulatory effect of Coca-Cola on gastroduodenal HCO3- secretion in rats.

    Science.gov (United States)

    Sasaki, Y; Aihara, E; Ise, F; Kita, K; Takeuchi, K

    2007-10-01

    We examined the effect of various carbonated beverages, especially Coca-Cola, on the HCO3- secretion in the rat stomach and duodenum. Under urethane anaesthesia, a chambered stomach or a proximal duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. The amount of CO2 contained in these beverages was about 4-7 g/mL. Coca-Cola topically applied to the mucosa for 10 min significantly increased the HCO3- secretion in both the stomach and the duodenum. The HCO3- response in the duodenum was totally abolished by indomethacin and also partially inhibited by acetazolamide, an inhibitor of carbonic anhydrase. Likewise, the response in the stomach was also markedly inhibited by either acetazolamide or indomethacin. The mucosal application of Coca-Cola increased the PGE2 contents in both the stomach and the duodenum. Other carbonated beverages, such as sparkling water, Fanta Grape or cider, also increased the HCO3- secretion in these tissues. These results suggest that Coca-Cola induces HCO3- secretion in both the stomach and the duodenum, and these responses may be attributable to both the intracellular supply of HCO3- generated via carbonic anhydrase, and endogenous PGs, probably related to the acidic pH of the solution.

  13. Evidence for the role of a Na(+)/HCO(3)(-) cotransporter in trout hepatocyte pHi regulation.

    Science.gov (United States)

    Furimsky, M; Moon, T W; Perry, S F

    2000-07-01

    The mechanisms of intracellular pH (pHi) regulation were examined in hepatocytes of the rainbow trout Oncorhynchus mykiss. pHi was monitored using the pH-sensitive fluorescent dye BCECF, and the effects of various media and pharmacological agents were examined for their influence on baseline pHi and recovery rates from acid and base loading. Rates of Na(+) uptake were measured using (22)Na, and changes in membrane potential were examined using the potentiometric fluorescent dye Oxonol VI. The rate of proton extrusion following acid loading was diminished by the blockade of either Na(+)/H(+) exchange (using amiloride) or anion transport (using DIDS). The removal of external HCO(3)(-) and the abolition of outward K(+) diffusion by the channel blocker Ba(2+) also decreased the rate of proton extrusion following acid load. Depolarization of the cell membrane with 50 mmol l(-)(1) K(+), however, did not affect pHi. The rate of recovery from base loading was significantly diminished by the blockade of anion transport, removal of external HCO(3)(-) and, to a lesser extent, by blocking Na(+)/H(+) exchange. The blockade of K(+) conductance had no effect. The decrease in Na(+) uptake rate observed in the presence of the anion transport blocker DIDS and the DIDS-sensitive hyperpolarization of membrane potential during recovery from acid loading suggest that a Na(+)-dependent electrogenic transport system is involved in the restoration of pHi after intracellular acidification. The effects on baseline pHi indicate that the different membrane exchangers are tonically active in the maintenance of steady-state pHi. This study confirms the roles of a Na(+)/H(+) exchanger and a Cl(-)/HCO(3)(-) exchanger in the regulation of trout hepatocyte pHi and provides new evidence that a Na(+)/HCO(3)(-) cotransporter contributes to pHi regulation.

  14. Photodetachment of Isolated Bicarbonate Anion: Electron Binding Energy of HCO3-

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xue B.; Xantheas, Sotiris S.

    2011-04-29

    We report the first direct photodetachment photoelectron spectroscopy of HCO3 in the gas phase under low temperature conditions. The observed photoelectron spectra are complicated due to excitations of manifolds in both vibrational and electronic states. A long and single vibrational progression with a frequency of 530 ± 20 cm-1 is partially resolved in the threshold of the T=20 K, 266 nm spectrum. The adiabatic electron detachment energy (ADE) of HCO3, or in other words the electron affinity (EA) of neutral HCO3, is experimentally determined from the (0-0) transition to be 3.680 ± 0.015 eV. High-level ab initio calculations at the CCSD(T) level of theory produce an anharmonic frequency of 546 cm-1 for HCO3 and a value of 3.62 eV for the (0,0) transition, both in excellent agreement with the experimentally determined values.

  15. Effects of CO2-HCO3- on catecholamine efflux from cat carotid body.

    Science.gov (United States)

    Iturriaga, R; Alcayaga, J

    1998-01-01

    Using a chronoamperometric technique with carbon-fiber microelectrodes and neural recordings, we simultaneously measured the effects of the following procedures on catecholamine efflux (delta CA) and frequency of chemosensory discharges (fx) from superfused cat carotid body: 1) the addition of CO2-HCO3- to Tyrode solution previously buffered with N-2-hydroxyethylpiperazine-N'-2-ethane-sulfonic acid, maintaining pH at 7.40; 2) hypercapnia (10% CO2, pH 7.10); 3) hypoxia (PO2 h approximately 40 Torr) with and without CO2-HCO3-; and 4) the impact of several boluses of dopamine (DA; 10-100 micrograms) on hypoxic and hypercapnic challenges. With CO2-HCO3-, hypoxia increased fx which preceded delta CA increases, whereas hypercapnia raised fx but did not consistently increase delta CA. Repeated stimuli induced similar fx increases, but attenuated delta CA. After DA, hypoxia produced larger delta CA, which preceded chemosensory responses. Without CO2-HCO3-, hypoxia produced a similar pattern of delta CA and fx responses. Switching to Tyrode solution with CO2-HCO3- at pH 7.40 raised fx but did not increase delta CA. With CO2-HCO3- and after DA, hypoxic-induced delta CAs were larger than in its absence. Results suggest that DA release is not essential for chemosensory excitation.

  16. H2S-induced HCO3- secretion in the rat stomach--involvement of nitric oxide, prostaglandins, and capsaicin-sensitive sensory neurons.

    Science.gov (United States)

    Takeuchi, Koji; Ise, Fumitaka; Takahashi, Kento; Aihara, Eitaro; Hayashi, Shusaku

    2015-04-30

    Hydrogen sulfide (H2S) is known to be an important gaseous mediator that affects various functions under physiological and pathological conditions. We examined the effects of NaHS, a H2S donor, on HCO3(-) secretion in rat stomachs and investigated the mechanism involved in this response. Under urethane anesthesia, rat stomachs were mounted on an ex vivo chamber and perfused with saline. Acid secretion had been inhibited by omeprazole. The secretion of HCO3(-) was measured at pH 7.0 using a pH-stat method and by the addition of 10 mM HCl. NaHS (0.5-10 mM) was perfused in the stomach for 5 min. Indomethacin or L-NAME was administered s.c. before NaHS treatment, while glibenclamide (a KATP channel blocker), ONO-8711 (an EP1 antagonist), or propargylglycine (a cystathionine γ-lyase inhibitor) was given i.p. before. The mucosal perfusion of NaHS dose-dependently increased the secretion of HCO3(-), and this effect was significantly attenuated by indomethacin, L-NAME, and sensory deafferentation, but not by glibenclamide or ONO-8711. The luminal output of nitric oxide, but not the mucosal production of prostaglandin E2, was increased by the perfusion of NaHS. Mucosal acidification stimulated HCO3(-) secretion, and this response was inhibited by sensory deafferentation, indomethacin, L-NAME, and ONO-8711, but not by propargylglycine. These results suggested that H2S increased HCO3(-) secretion in the stomach, and this effect was mediated by capsaicin-sensitive afferent neurons and dependent on nitric oxide and prostaglandins, but not ATP-sensitive K(+) channels. Further study is needed to define the role of endogenous H2S in the mechanism underlying acid-induced gastric HCO3(-) secretion. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Chloride binding site of neurotransmitter sodium symporters

    DEFF Research Database (Denmark)

    Kantcheva, Adriana Krassimirova; Quick, Matthias; Shi, Lei

    2013-01-01

    Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT are chloride-independent but contain an acidic residue (Glu290 in LeuT) at a site where eukaryotic NSSs...

  18. Evaluation the anaerobic digestion performance of solid residual kitchen waste by NaHCO3 buffering

    International Nuclear Information System (INIS)

    Gao, Shumei; Huang, Yue; Yang, Lili; Wang, Hao; Zhao, Mingxing; Xu, Zhiyang; Huang, Zhenxing; Ruan, Wenquan

    2015-01-01

    Highlights: • The maximum methane production of SRKW was 479 mL/gTS added . • Anaerobic digestion capacity increased by 33.3% through NaHCO 3 buffering. • Protease activity was mainly affected by high organic load. - Abstract: Anaerobic digestion has been considered as a promising energy-producing process for kitchen waste treatment. In this paper, the anaerobic digestion (AD) performances of solid residual kitchen waste (SRKW) with or without NaHCO 3 buffering were investigated. The results indicated that the methane production reached the maximum of 479 mL/gTS added at the inoculum to substrate ratio (ISR, based on VS) of 1:1.4 without buffering, accompanied by VS removal rate of 78.91%. Moreover, the anaerobic digestion capacity increased by 33.3% through NaHCO 3 buffering, and the methane yield at ISR 1:2.8 was improved by 48.5% with NaHCO 3 addition. However, the methanogenesis with or without NaHCO 3 buffer was suppressed at ISR 1:3.5, indicated from the lowest methane yield of 55.50 mL/gTS added and high volatile fatty acids concentration of more than 14,000 mg/L. Furthermore, proteins in SRKW were not degraded completely at excessive organic loading, since the concentrations of ammonia nitrogen in ISR 1:3.5 groups with (2738 mg/L) and without NaHCO 3 buffering (2654 mg/L) were lower than the theoretical value of 3500 mg/L and the protease activities in ISR 1:3.5 groups were also inhibited

  19. NH4HCO3 gas-generating liposomal nanoparticle for photoacoustic imaging in breast cancer

    Directory of Open Access Journals (Sweden)

    Xia J

    2017-03-01

    Full Text Available Jizhu Xia, Gang Feng, Xiaorong Xia, Lan Hao, Zhigang Wang Chongqing Key Laboratory of Ultrasound Molecular Imaging, Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Abstract: In this study, we have developed a biodegradable nanomaterial for photoacoustic imaging (PAI. Its biodegradation products can be fully eliminated from a living organism. It is a gas-generating nanoparticle of liposome-encapsulating ammonium bicarbonate (NH4HCO3 solution, which is safe, effective, inexpensive, and free of side effects. When lasers irradiate these nanoparticles, NH4HCO3 decomposes to produce CO2, which can absorb much of the light energy under laser irradiation with a specific wavelength, and then expand under heat to generate a thermal acoustic wave. An acoustic detector can detect this wave and show it as a photoacoustic signal on a display screen. The intensity of the photoacoustic signal is enhanced corresponding to an increase in time, concentration, and temperature. During in vivo testing, nanoparticles were injected into tumor-bearing nude mice through the caudal vein, and photoacoustic signals were detected from the tumor, reaching a peak in 4 h, and then gradually disappearing. There was no damage to the skin or subcutaneous tissue from laser radiation. Our developed gas-generating nanomaterial, NH4HCO3 nanomaterial, is feasible, effective, safe, and inexpensive. Therefore, it is a promising material to be used in clinical PAI. Keywords: Photoacoustic tomography, CO2, NH4HCO3, contrast agent, cancer

  20. Identification and Analysis of NaHCO3 Stress Responsive Genes in Wild Soybean (Glycine soja Roots by RNA-seq

    Directory of Open Access Journals (Sweden)

    Jinlong Zhang

    2016-12-01

    Full Text Available Soil alkalinity is a major abiotic constraint to crop productivity and quality. Wild soybean (Glycine soja is considered to be more stress-tolerant than cultivated soybean (G. max, and has considerable genetic variation for increasing alkalinity tolerance of soybean. In this study, we analyzed the transcriptome profile in the roots of an alkalinity tolerant wild soybean variety N24852 at 12 and 24 h after 90 mM NaHCO3 stress by RNA-sequencing. Compared with the controls, a total of 449 differentially expressed genes (DEGs were identified, including 95 and 140 up-regulated genes, and 108 and 135 down-regulated genes at 12 and 24 h after NaHCO3 treatment, respectively. Quantitative RT-PCR analysis of 14 DEGs showed a high consistency with their expression profiles by RNA-sequencing. Gene Ontology (GO terms related to transcription factors and transporters were significantly enriched in the up-regulated genes at 12 and 24 h after NaHCO3 stress, respectively. Nuclear Factor Y subunit A (NF-YA transcription factors were enriched at 12 h after NaHCO3 stress, and high percentages of basic helix-loop-helix (bHLH, ethylene-responsive factor (ERF, Trihelix and zinc finger (C2H2, C3H transcription factors were found at both 12 and 24 h after NaHCO3 stress. Genes related to ion transporters such as ABC transporter, aluminum activated malate transporter (ALMT, glutamate receptor (GLR, nitrate transporter (NRT / proton dependent oligopeptide (POT family, and S-type anion channel (SLAH were enriched in up-regulated DEGs at 24 h after NaHCO3 treatment, implying their roles in maintaining ion homeostasis in soybean roots under alkalinity. KEGG pathway enrichment analysis showed phenylpropanoid biosynthesis and phenylalanine metabolism pathways might participate in soybean response to alkalinity. This study provides a foundation to further investigate the functions of NaHCO3 stress-responsive genes and the molecular basis of soybean tolerance to alkalinity.

  1. One for two: conversion of waste chicken feathers to carbon microspheres and (NH4)HCO3.

    Science.gov (United States)

    Gao, Lei; Hu, Haibo; Sui, Xuelin; Chen, Changle; Chen, Qianwang

    2014-06-03

    Pyrolysis of 1 g of waste chicken feathers (quills and barbs) in supercritical carbon dioxide (sc-CO2) system at 600 °C for 3 h leads to the formation of 0.25 g well-shaped carbon microspheres with diameters of 1-5 μm and 0.26 g ammonium bicarbonate ((NH4)HCO3). The products were characterized by powder X-ray diffraction (XRD), Field emission scanning electron microscopy (FE-SEM), Raman spectroscopic, FT-IR spectrum, X-ray electron spectroscopy (XPS), and N2 adsorption/desorption measurements. The obtained carbon microspheres displayed great superhydrophobicity as fabric coatings materials, with the water contact angle of up to 165.2±2.5°. The strategy is simple, efficient, does not require any toxic chemicals or catalysts, and generates two valuable materials at the same time. Moreover, other nitrogen-containing materials (such as nylon and amino acids) can also be converted to carbon microspheres and (NH4)HCO3 in the sc-CO2 system. This provides a simple strategy to extract the nitrogen content from natural and man-made waste materials and generate (NH4)HCO3 as fertilizer.

  2. Investigations on the properties of NH4HCO3 filled natural rubber based magnetorheological elastomers (MREs)

    Science.gov (United States)

    Fan, Lili; Wang, Guoping; Wang, Wenju; Shi, Guanxin; Yang, Fufeng; Rui, Xiaoting

    2018-04-01

    Various anisotropic magnetorheological elastomers (MREs) were synthesized using the rubber mixing technique. Magnetic and temperature distributions of the experimental equipment and test instruments were analyzed by the ANSYS. NH4HCO3 was filled in the natural rubber matrix to modify properties of MREs. Microstructures and compositions of samples were studied by the scanning electron microscope (SEM), the energy dispersive x-ray spectroscopy (EDAX) analysis and x-ray powder diffraction (XRD). Via vibrating sample magnetometer (VSM) and density functional theory (DFT) method, the magnetic property of carbonyl iron (CI) was illuminated. The shear storage modulus and MR effect of MREs were investigated by the dynamic mechanical analyzer (DMA). It indicated that distributions of magnetic and temperature in the experimental and testing devices were uniform. Before vulcanization, CI particles were uniformly distributed in the matrix, while a CI chain structure was formed and embedded in the matrix after the vulcanization process. Moderate addition of NH4HCO3 accelerated the rubber vulcanization and enhanced the MR effect.

  3. DNA Methylation Influences Chlorogenic Acid Biosynthesis in Lonicera japonica by Mediating LjbZIP8 to Regulate Phenylalanine Ammonia-Lyase 2 Expression

    Directory of Open Access Journals (Sweden)

    Liangping Zha

    2017-07-01

    Full Text Available The content of active compounds differ in buds and flowers of Lonicera japonica (FLJ and L. japonica var. chinensis (rFLJ. Chlorogenic acid (CGAs were major active compounds of L. japonica and regarded as measurements for quality evaluation. However, little is known concerning the formation of active compounds at the molecular level. We quantified the major CGAs in FLJ and rFLJ, and found the concentrations of CGAs were higher in the buds of rFLJ than those of FLJ. Further analysis of CpG methylation of CGAs biosynthesis genes showed differences between FLJ and rFLJ in the 5′-UTR of phenylalanine ammonia-lyase 2 (PAL2. We identified 11 LjbZIP proteins and 24 rLjbZIP proteins with conserved basic leucine zipper domains, subcellular localization, and electrophoretic mobility shift assay showed that the transcription factor LjbZIP8 is a nuclear-localized protein that specifically binds to the G-box element of the LjPAL2 5′-UTR. Additionally, a transactivation assay and LjbZIP8 overexpression in transgenic tobacco indicated that LjbZIP8 could function as a repressor of transcription. Finally, treatment with 5-azacytidine decreased the transcription level of LjPAL2 and CGAs content in FLJ leaves. These results raise the possibility that DNA methylation might influence the recruitment of LjbZIP8, regulating PAL2 expression level and CGAs content in L. japonica.

  4. Contraception with RISUG® and functional reversal through DMSO and NaHCO3 in male rabbits.

    Science.gov (United States)

    Ansari, Abdul S; Badar, Ayesha; Balasubramanian, Krithika; Lohiya, Nirmal K

    2017-01-01

    The study aimed to evaluate reversal of short- and long-term vas occlusion with reversible inhibition of sperm under guidance (RISUG) using dimethyl sulfoxide (DMSO) and sodium bicarbonate (NaHCO3) in male rabbits (Oryctolagus cuniculus). Animals were divided into seven groups containing five animals each. Fortnightly, semen analysis revealed that sperm concentration and output steadily declined after vas occlusion and complete azoospermia was attained at 30-60 days postinjection. Spermatozoa reappeared at 60-75 days of reversal and normozoospermia was noticed between 135 days and 150 days in the reversal groups. All spermatozoa were found nonmotile prior to azoospermia and a gradual recovery in sperm motility was observed between 105 days and 135 days of reversal. A significant decline in viability of sperms was noticed during vas occlusion up to 30-60 days which recovered at 60-75 days postreversal and normalized by 75-105 days in the reversal groups. A significant enhancement in the sperm abnormalities was recorded in all vas occluded animals as well as those in initial periods of reversal. Other parameters, namely, semen volume, ejaculation time, pH, color, and consistency, remained unaltered during all phases of the study. Fertility test, at the intervals of 15 days, demonstrated that animals exhibited complete sterility during the entire period of vas occlusion. A gradual recovery in fertility was observed with the appearance of spermatozoa following vas occlusion reversal and 100% fertility was observed following 135-150 days of reversal. F1 progeny of reversed animals was found normal. The results suggest that reversal with DMSO or NaHCO3 is feasible, with normal progeny, following short- and long-term contraception.

  5. Increased NBCn1 expression, Na+/ HCO 3 ? co-transport and intracellular pH in human vascular smooth muscle cells with a risk allele for hypertension

    OpenAIRE

    Ng, Fu Liang; Boedtkjer, Ebbe; Witkowska, Kate; Ren, Meixia; Zhang, Ruoxin; Tucker, Arthur; Aalkj?r, Christian; Caulfield, Mark J.; Ye, Shu

    2017-01-01

    Abstract Genome-wide association studies have revealed an association between variation at the SLC4A7 locus and blood pressure. SLC4A7 encodes the electroneutral Na+/ HCO 3 ? co-transporter NBCn1 which regulates intracellular pH (pH i ). We conducted a functional study of variants at this locus in primary cultures of vascular smooth muscle and endothelial cells. In both cell types, we found genotype-dependent differences for rs13082711 in DNA-nuclear protein interactions, where the risk allel...

  6. Abnormal duodenal [HCO3-] following secretin stimulation develops sooner than endocrine insufficiency in minimal change chronic pancreatitis.

    Science.gov (United States)

    Pelley, Joshua R; Gordon, Stuart R; Gardner, Timothy B

    2012-04-01

    Direct pancreatic function tests (PFTs) are often used to diagnose chronic pancreatitis (CP). We aimed to determine the temporal relationship between an abnormal PFT result, cross-sectional imaging, and clinical symptoms. All patients referred for endoscopic ultrasound (EUS) and PFT for suspected CP at our medical center from 2008 to 2010 were included. Each subject underwent EUS and PFT on the same day using secretin stimulation. Seventeen patients had duodenal HCO3 values of less than 80 mEq/L and were labeled as abnormal; the 25 other patients had at least 1 duodenal HCO3 values of 80 mEq/L or greater. Patients with abnormal PFTs had more parenchymal (2.0 vs 0.92, P = 0.012), ductal (1.18 vs 0.6, P = 0.036), and total features (3.18 vs 1.52, P = 0.009) than those with normal PFTs on EUS examination. There was no difference in regard to the frequency of abnormal CT scans (25% vs 15%, P = 0.139), diarrhea (67% vs 60%, P = 0.463), fat-soluble vitamin deficiency (33% vs 26%, P = 0.315), or diabetes (10% vs 4%, P = 0.066). Patients with equivocal imaging and abnormally low duodenal HCO3 have more EUS features of CP than do patients with normal duodenal HCO3 values, suggesting that low duodenal HCO3 values are among the first measurable abnormalities in CP.

  7. TESTING THE GLOBAL STAR FORMATION RELATION: AN HCO+ (3-2) MAPPING STUDY OF RED MSX SOURCES IN THE BOLOCAM GALACTIC PLANE SURVEY

    International Nuclear Information System (INIS)

    Schenck, David E.; Shirley, Yancy L.; Reiter, Megan; Juneau, Stephanie

    2011-01-01

    We present an analysis of the relation between the star formation rate (SFR) and mass of dense gas in Galactic clumps and nearby galaxies. Using the bolometric luminosity as a measure of SFR and the molecular line luminosity of HCO + (3-2) as a measure of dense gas mass, we find that the relation between SFR and M dense is approximately linear. This is similar to published results derived using HCN (1-0) as a dense gas tracer. HCO + (3-2) and HCN (1-0) have similar conditions for excitation. Our work includes 16 Galactic clumps that are in both the Bolocam Galactic Plane Survey and the Red MSX Source Survey, 27 water maser sources from the literature, and the aforementioned HCN (1-0) data. Our results agree qualitatively with predictions of recent theoretical models which state that the nature of the relation should depend on how the critical density of the tracer compares with the mean density of the gas.

  8. Effect of sodium bicarbonate on [HCO3-], pH, and gastrointestinal symptoms.

    Science.gov (United States)

    Carr, Amelia J; Slater, Gary J; Gore, Christopher J; Dawson, Brian; Burke, Louise M

    2011-06-01

    Sodium bicarbonate (NaHCO₃) is often ingested at a dose of 0.3 g/kg body mass (BM), but ingestion protocols are inconsistent in terms of using solution or capsules, ingestion period, combining NaHCO₃ with sodium citrate (Na₃C₆H₅O₇), and coingested food and fluid. To quantify the effect of ingesting 0.3 g/kg NaHCO₃ on blood pH, [HCO₃-], and gastrointestinal (GI) symptoms over the subsequent 3 hr using a range of ingestion protocols and, thus, to determine an optimal protocol. In a crossover design, 13 physically active subjects undertook 8 NaHCO₃ experimental ingestion protocols and 1 placebo protocol. Capillary blood was taken every 30 min and analyzed for pH and [HCO₃-]. GI symptoms were quantified every 30 min via questionnaire. Statistics used were pairwise comparisons between protocols; differences were interpreted in relation to smallest worthwhile changes for each variable. A likelihood of >75% was a substantial change. [HCO₃-] and pH were substantially greater than in placebo for all other ingestion protocols at almost all time points. When NaHCO3 was coingested with food, the greatest [HCO₃-] (30.9 mmol/kg) and pH (7.49) and lowest incidence of GI symptoms were observed. The greatest incidence of GI side effects was observed 90 min after ingestion of 0.3 g/kg NaHCO₃ solution. The changes in pH and [HCO₃-] for the 8 NaHCO₃-ingestion protocols were similar, so an optimal protocol cannot be recommended. However, the results suggest that NaHCO₃ coingested with a high-carbohydrate meal should be taken 120-150 min before exercise to induce substantial blood alkalosis and reduce GI symptoms.

  9. Influence of magnesium sulfate on HCO3/Cl transmembrane exchange rate in human erythrocytes.

    Science.gov (United States)

    Chernyshova, Ekaterina S; Zaikina, Yulia S; Tsvetovskaya, Galina A; Strokotov, Dmitry I; Yurkin, Maxim A; Serebrennikova, Elena S; Volkov, Leonid; Maltsev, Valeri P; Chernyshev, Andrei V

    2016-03-21

    Magnesium sulfate (MgSO4) is widely used in medicine but molecular mechanisms of its protection through influence on erythrocytes are not fully understood and are considerably controversial. Using scanning flow cytometry, in this work for the first time we observed experimentally (both in situ and in vitro) a significant increase of HCO3(-)/Cl(-) transmembrane exchange rate of human erythrocytes in the presence of MgSO4 in blood. For a quantitative analysis of the obtained experimental data, we introduced and verified a molecular kinetic model, which describes activation of major anion exchanger Band 3 (or AE1) by its complexation with free intracellular Mg(2+) (taking into account Mg(2+) membrane transport and intracellular buffering). Fitting the model to our in vitro experimental data, we observed a good correspondence between theoretical and experimental kinetic curves that allowed us to evaluate the model parameters and to estimate for the first time the association constant of Mg(2+) with Band 3 as KB~0.07mM, which is in agreement with known values of the apparent Mg(2+) dissociation constant (from 0.01 to 0.1mM) that reflects experiments on enrichment of Mg(2+) at the inner erythrocyte membrane (Gunther, 2007). Results of this work partly clarify the molecular mechanisms of MgSO4 action in human erythrocytes. The method developed allows one to estimate quantitatively a perspective of MgSO4 treatment for a patient. It should be particularly helpful in prenatal medicine for early detection of pathologies associated with the risk of fetal hypoxia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Methane explosion suppression characteristics based on the NaHCO3/red-mud composite powders with core-shell structure.

    Science.gov (United States)

    Wang, Yan; Cheng, Yi-Shen; Yu, Ming-Gao; Li, Yao; Cao, Jian-Liang; Zheng, Li-Gang; Yi, Hong-Wei

    2017-08-05

    The NaHCO 3 /red-mud (RM) composite powders were successfully prepared by the solvent-anti-solvent method for methane explosion suppression. The RM was used as a carrier, and the NaHCO 3 was used as a loaded inhibitor. The NaHCO 3 /RM composite powders showed a special core-shell structure and excellent endothermic performance. The suppression properties of NaHCO 3 /RM composite for 9.5% CH 4 explosion were tested in a 20L spherical explosion vessel and a 5L Perspex duct. The results showed that the NaHCO 3 /RM composite powders displayed a much better suppression property than the pure RM or NaHCO 3 powders. The loading amount of NaHCO 3 has an intensive influence on the inhibition property of NaHCO 3 /RM composite powders. The best loaded content of NaHCO 3 is 35%. It exhibited significant inhibitory effect that the explosion max-pressure declined 44.9%, the max-pressure rise rate declined 96.3% and the pressure peak time delayed 366.7%, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Strong shift from HCO3 (-) to CO 2 uptake in Emiliania huxleyi with acidification: new approach unravels acclimation versus short-term pH effects.

    Science.gov (United States)

    Kottmeier, Dorothee M; Rokitta, Sebastian D; Tortell, Philippe D; Rost, Björn

    2014-09-01

    Effects of ocean acidification on Emiliania huxleyi strain RCC 1216 (calcifying, diploid life-cycle stage) and RCC 1217 (non-calcifying, haploid life-cycle stage) were investigated by measuring growth, elemental composition, and production rates under different pCO2 levels (380 and 950 μatm). In these differently acclimated cells, the photosynthetic carbon source was assessed by a (14)C disequilibrium assay, conducted over a range of ecologically relevant pH values (7.9-8.7). In agreement with previous studies, we observed decreased calcification and stimulated biomass production in diploid cells under high pCO2, but no CO2-dependent changes in biomass production for haploid cells. In both life-cycle stages, the relative contributions of CO2 and HCO3 (-) uptake depended strongly on the assay pH. At pH values ≤ 8.1, cells preferentially used CO2 (≥ 90 % CO2), whereas at pH values ≥ 8.3, cells progressively increased the fraction of HCO3 (-) uptake (~45 % CO2 at pH 8.7 in diploid cells; ~55 % CO2 at pH 8.5 in haploid cells). In contrast to the short-term effect of the assay pH, the pCO2 acclimation history had no significant effect on the carbon uptake behavior. A numerical sensitivity study confirmed that the pH-modification in the (14)C disequilibrium method yields reliable results, provided that model parameters (e.g., pH, temperature) are kept within typical measurement uncertainties. Our results demonstrate a high plasticity of E. huxleyi to rapidly adjust carbon acquisition to the external carbon supply and/or pH, and provide an explanation for the paradoxical observation of high CO2 sensitivity despite the apparently high HCO3 (-) usage seen in previous studies.

  12. Analysis of expressed sequence tags from a NaHCO(3)-treated alkali-tolerant plant, Chloris virgata.

    Science.gov (United States)

    Nishiuchi, Shunsaku; Fujihara, Kazumasa; Liu, Shenkui; Takano, Tetsuo

    2010-04-01

    Chloris virgata Swartz (C. virgata) is a gramineous wild plant that can survive in saline-alkali areas in northeast China. To examine the tolerance mechanisms of C. virgata, we constructed a cDNA library from whole plants of C. virgata that had been treated with 100 mM NaHCO(3) for 24 h and sequenced 3168 randomly selected clones. Most (2590) of the expressed sequence tags (ESTs) showed significant similarity to sequences in the NCBI database. Of the 2590 genes, 1893 were unique. Gene Ontology (GO) Slim annotations were obtained for 1081 ESTs by BLAST2GO and it was found that 75 genes of them were annotated with GO terms "response to stress", "response to abiotic stimulus", and "response to biotic stimulus", indicating these genes were likely to function in tolerance mechanism of C. virgata. In a separate experiment, 24 genes that are known from previous studies to be associated with abiotic stress tolerance were further examined by real-time RT-PCR to see how their expressions were affected by NaHCO(3) stress. NaHCO(3) treatment up-regulated the expressions of pathogenesis-related gene (DC998527), Win1 precursor gene (DC998617), catalase gene (DC999385), ribosome inactivating protein 1 (DC999555), Na(+)/H(+) antiporter gene (DC998043), and two-component regulator gene (DC998236). Copyright 2010 Elsevier Masson SAS. All rights reserved.

  13. pH Regulation of Electrogenic Sugar/H+ Symport in MFS Sugar Permeases

    Science.gov (United States)

    Bazzone, Andre; Madej, M. Gregor; Kaback, H. Ronald

    2016-01-01

    Bacterial sugar symporters in the Major Facilitator Superfamily (MFS) use the H+ (and in a few cases Na+) electrochemical gradients to achieve active transport of sugar into the cell. Because a number of structures of MFS sugar symporters have been solved recently, molecular insight into the transport mechanism is possible from detailed functional analysis. We present here a comparative electrophysiological study of the lactose permease (LacY), the fucose permease (FucP) and the xylose permease (XylE), which reveals common mechanistic principles and differences. In all three symporters energetically downhill electrogenic sugar/H+ symport is observed. Comparison of the pH dependence of symport at symmetrical pH exhibits broad bell-shaped pH profiles extending over 3 to 6 pH units and a decrease at extremely alkaline pH ≥ 9.4 and at acidic to neutral pH = 4.6–7.5. The pH dependence can be described by an acidic to neutral apparent pK (pKapp) and an alkaline pKapp. Experimental evidence suggests that the alkaline pKapp is due to H+ depletion at the protonation site, while the acidic pKapp is due to inhibition of deprotonation. Since previous studies suggest that a single carboxyl group in LacY (Glu325) may be the only side chain directly involved in H+ translocation and a carboxyl side chain with similar properties has been identified in FucP (Asp46) and XylE (Asp27), the present results imply that the pK of this residue is switched during H+/sugar symport in all three symporters. PMID:27227677

  14. Surface generation of a cobalt-derived water oxidation electrocatalyst developed in a neutral HCO3 -/CO2 system

    KAUST Repository

    Joya, Khurram Saleem

    2014-06-04

    Neutral HCO3 -/CO2 is a new electrolyte system for in situ generation of robust and efficient Co-derived (Co-Ci) water oxidation electrocatalysts. The Co-Ci/indium tin oxide system shows a remarkable 2.0 mA cm-2 oxygen evolution current density that is sustained for several hours. 7.5 nmol of electroactive species per cm2 generates about 109 μmol of O2 at a rate of 0.51 per mol of catalyst per second.

  15. Surface generation of a cobalt-derived water oxidation electrocatalyst developed in a neutral HCO3 -/CO2 system

    KAUST Repository

    Joya, Khurram Saleem; Takanabe, Kazuhiro; De Groot, Huub J M

    2014-01-01

    Neutral HCO3 -/CO2 is a new electrolyte system for in situ generation of robust and efficient Co-derived (Co-Ci) water oxidation electrocatalysts. The Co-Ci/indium tin oxide system shows a remarkable 2.0 mA cm-2 oxygen evolution current density that is sustained for several hours. 7.5 nmol of electroactive species per cm2 generates about 109 μmol of O2 at a rate of 0.51 per mol of catalyst per second.

  16. Removing polysaccharides-and saccharides-related coloring impurities in alkyl polyglycosides by bleaching with the H2O2/TAED/NaHCO3 system.

    Science.gov (United States)

    Yanmei, Liu; Jinliang, Tao; Jiao, Sun; Wenyi, Chen

    2014-11-04

    The effect of H2O2/TAED/NaHCO3 system, namely NaHCO3 as alkaline agent with the (tetra acetyl ethylene diamine (TAED)) TAED-activated peroxide system, bleaching of alkyl polyglycosides solution was studied by spectrophotometry. The results showed that the optimal bleaching conditions about H2O2/TAED/NaHCO3 system bleaching of alkyl polyglycosides solution were as follows: molar ratio of TAED to H2O2 was 0.06, addition of H2O2 was 8.6%, addition of NaHCO3 was 3.2%, bleaching temperature of 50-65 °C, addition of MgO was 0.13%, and bleaching time was 8h. If too much amount of NaHCO3 was added to the system and maintained alkaline pH, the bleaching effect would be greatly reduced. Fixing molar ratio of TAED to H2O2 and increasing the amount of H2O2 were beneficial to improve the whiteness of alkyl polyglycosides, but adding too much amount of H2O2 would reduce the transparency. In the TAED-activated peroxide system, NaHCO3 as alkaline agent and buffer agent, could overcome the disadvantage of producing black precipitates when NaOH as alkaline agent. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Role of an extracellular loop in determining the stoichiometry of Na+–HCO3− cotransporters

    Science.gov (United States)

    Chen, Li-Ming; Liu, Ying; Boron, Walter F

    2011-01-01

    The Na+–HCO3− cotransporters (NBCs) of the solute carrier 4 family (SLC4) are critical for regulating pH in cells as well as in fluids such as blood and cerebrospinal fluid. Moreover, mutations and gene disruptions in NBC are linked to a wide range of pathologies. NBCe1 (SLC4A4) is electrogenic because it has an apparent Na+:HCO3− stoichiometry of 1:2 or 1:3, whereas NBCn1 (SLC4A7) is electroneutral because it has an apparent stoichiometry of 1:1. Because stoichiometry influences the effect of transport on membrane potential and vice versa, a central question is what structural features underlie electrogenicity versus electroneutrality. A previous study on rat NBCe1/n1 chimeras demonstrated that the structural elements determining the electrogenicity of NBCe1-A are located within the transmembrane domain, excluding the large third extracellular loop. In the present study we generated a series of chimeras of human NBCe1-A and human NBCn1-A. We found that replacing merely the predicted fourth extracellular loop (EL4) – containing 32 amino acid residues that include 7 prolines – of human NBCe1-A with EL4 of NBCn1-A creates an electroneutral NBC. The opposite switch converts an electroneutral construct to one with electrogenic properties. The introduction of an N-glycosylation site into EL4 confirms that at least a part of it is exposed to the extracellular fluid. We hypothesize that putative EL4 either contributes to the substrate-binding vestibule or indirectly influences substrate binding by interacting with one or more transmembrane segments, thereby controlling the nature of transport. PMID:21224233

  18. Cerebral interstitial tissue oxygen tension, pH, HCO3, CO2.

    Science.gov (United States)

    Charbel, F T; Hoffman, W E; Misra, M; Hannigan, K; Ausman, J I

    1997-10-01

    There are many techniques for monitoring the injured brain following trauma, subarachnoid hemorrhage, or surgery. It is thought that the major determinants for recovery of injured cerebral tissue are oxygen, glucose delivery, and the clearance of metabolites. These factors, at optimal levels, are probably responsible for the regaining of neuronal functions. These parameters are in turn dependent on the tissue's blood flow and metabolism. We have been using a single, compact, polyethylene sensor, the Paratrend 7 for the measurement of cerebral oxygen tension, CO2, pH, and temperature. This sensor is designed for continuous blood gas analysis to aid in monitoring neurosurgical patients, both during surgery and in the intensive care unit. Using the Paratrend 7 sensor, we found the normal range of values to be: PO2 33 +/- 11 mm Hg; PCO2 48 +/- 7 mm Hg; pH 7.19 +/- 0.11. Critical measurements are considered to be tissue PO2 60 mm Hg, and pH effective method of measuring tissue cerebral oxygen tension, along with carbon dioxide levels, pH, and temperature.

  19. Neurotransmitter: Sodium Symporters: Caught in the Act!

    DEFF Research Database (Denmark)

    Malinauskaite, Lina

    The neurotransmitter: sodium symporters in the neurons. Communication between neurons is mediated by the release of molecules called neurotransmitters (blue dots) from first neuron and sensed by receptors on the surface of the second (purple sphere). The signal is ended by active reuptake...

  20. Transition metal ion FRET uncovers K(+) regulation of a neurotransmitter/sodium symporter

    DEFF Research Database (Denmark)

    Billesbølle, Christian B; Mortensen, Jonas S; Sohail, Azmat

    2016-01-01

    Neurotransmitter/sodium symporters (NSSs) are responsible for Na(+)-dependent reuptake of neurotransmitters and represent key targets for antidepressants and psychostimulants. LeuT, a prokaryotic NSS protein, constitutes a primary structural model for these transporters. Here we show that K...

  1. Relationship between HCO_3"- concentration to weight of C_6H_6 of environmental isotop "1"4C analysis and its relationship with sampling in the field

    International Nuclear Information System (INIS)

    Satrio; Rasi Prasetio

    2016-01-01

    It has been done the groundwater sampling process of deep aquifer in Jakarta and surrounding areas for the analysis of environmental isotope "1"4C. Groundwater sampling was preceded by calculating the concentration of HCO_3"- (bicarbonate ion) through titration in the field. The number of repetitions of sampling is determined by the concentration data of HCO_3"- which obtained. The Repetition of this sampling will determine the acquisition of a solution of C_6H_6 (benzene) during the synthesis process benzene. In the field, the sampling is done by extracting of 60 liters of water to precipitate BaCO_3. The sampling process is repeated based on data from the bicarbonate ion concentration. The purpose of this study to determine the relationship between the concentration of HCO_3"- to the weights C_6H_6 which obtained in the analysis of environmental isotope "1"4C and evaluate the number of repetitions of the sampling that should be done. Based on the analysis of titration in the field, shows that concentration HCO_3"- ranged between 180 - 600 ppm with the acquisition of benzene between 1.84 to 4.5 grams. There is a strong relationship between the concentration of HCO_3"- and C_6H_6 weights obtained in the process of synthesis of benzene with a correlation of about 0.900. This correlation can be improved by measuring the concentration of HCO_3"- in advance in the laboratory tend to be more accurate than in the field. (author)

  2. Modeling of the Mixed Solvent Electrolyte System CO2-Na2CO3-NaHCO3-Monoethylene Glycol-Water

    DEFF Research Database (Denmark)

    Fosbøl, Philip Loldrup; Thomsen, Kaj; Stenby, Erling Halfdan

    2009-01-01

    The extended UNIQUAC electrolyte activity coefficient model has been correlated to 751 experimental solid−liquid equilibrium (SLE), vapor−liquid equilibrium (VLE), and excess enthalpy data for the mixed solvent CO2−NaHCO3−Na2CO3−monoethylene glycol(MEG)−H2O electrolyte system. The model...

  3. Effects of sodium bicarbonate on the end-tidal CO2, PaCO2, HCO3-, PH and cerebral blood flow

    International Nuclear Information System (INIS)

    Komatani, Akio; Akutsu, Tooru; Yoshida, Michihiko; Yamaguchi, Koichi; Seo, Hiroshi

    1992-01-01

    To estimate the quantitative reactivity of cerebral blood flow (CBF), the effects of sodium bicarbonate on the end-tidal CO 2 , arterial partial pressure of CO 2 (PaCO 2 ), HCO 3 - , pH and CBF were examined. The CBF was measured by 133 Xe inhalation method with ring type SPECT (HEADTOME). Activation study with sodium bicarbonate administration was performed after 30 minutes of resting study, and the reactivity of each parameters was investigated. The arterial HCO 3 - and pH increased with similar reactivity, but PaCO 2 , end-tidal CO 2 and CBF in the non-injured hemisphere changed with irregular reactivity. The excellent correlation between PaCO 2 and end-tidal CO 2 was vanished by the administration of sodium bicarbonate. The reactivity of CBF did not correlate with reactivity of PaCO 2 and end-tidal CO 2 , but correlated with arterial HCO 3 - and pH. Thus the measurement of arterial HCO 3 - and pH may be indispensable to estimate the CBF reactivity with the administration of sodium bicarbonate. (author)

  4. Integrated responses of Na+/HCO3- cotransporters and V-type H+-ATPases in the fish gill and kidney during respiratory acidosis.

    Science.gov (United States)

    Perry, S F; Furimsky, M; Bayaa, M; Georgalis, T; Shahsavarani, A; Nickerson, J G; Moon, T W

    2003-12-30

    Using degenerate primers, followed by 3' and 5' RACE and "long" PCR, a continuous 4050-bp cDNA was obtained and sequenced from rainbow trout (Oncorhynchus mykiss) gill. The cDNA included an open reading frame encoding a deduced protein of 1088 amino acids. A BLAST search of the GenBank protein database demonstrated that the trout gene shared high sequence similarity with several vertebrate Na(+)/HCO(3)(-) cotransporters (NBCs) and in particular, NBC1. Protein alignment revealed that the trout NBC is >80% identical to vertebrate NBC1s and phylogenetic analysis provided additional evidence that the trout NBC is indeed a homolog of NBC1. Using the same degenerate primers, a partial cDNA (404 bp) for NBC was obtained from eel (Anguilla rostrata) kidney. Analysis of the tissue distribution of trout NBC, as determined by Northern blot analysis and real-time PCR, indicated high transcript levels in several absorptive/secretory epithelia including gill, kidney and intestine and significant levels in liver. NBC mRNA was undetectable in eel gill by real-time PCR. In trout, the levels of gill NBC1 mRNA were increased markedly during respiratory acidosis induced by exposure to hypercarbia; this response was accompanied by a transient increase in branchial V-type H(+)-ATPase mRNA levels. Assuming that the branchial NBC1 is localised to basolateral membranes of gill cells and operates in the influx mode (HCO(3)(-) and Na(+) entry into the cell), it would appear that in trout, the expression of branchial NBC1 is transcriptionally regulated to match the requirements of gill pHi regulation rather than to match trans-epithelial HCO(3)(-) efflux requirements for systemic acid-base balance. By analogy with mammalian systems, NBC1 in the kidney probably plays a role in the tubular reabsorption of both Na(+) and HCO(3)(-). During periods of respiratory acidosis, levels of renal NBC1 mRNA increased (after a transient reduction) in both trout and eel, presumably to increase HCO(3

  5. Influence of extracellular HCO3- and pH on lysine (LYS) and leucine (LEU) uptake and metabolism in swine renal tubules

    International Nuclear Information System (INIS)

    Patience, J.F.; Esteve-Garcia, E.; Austic, R.E.

    1986-01-01

    Fragments of renal tubules prepared by collagenase treatment of renal cortex were suspended to Krebs-Henseleit buffers which were modified to contain 10, 25 and 35 mM HCO 3 - at pH 7.4, or 25 mM HCO 3 - at pH 7.1, 7.4 and 7.7. Buffers were oxygenated with O 2 -CO 2 gas mixtures varying in carbon dioxide concentration prior to incubation. Approximately 100 mg tubules were incubated with shaking at 37 0 C for 30 min in serum-stoppered 25 ml Erlenmeyer flasks in 3.0 ml of buffer containing 0.1% dialyzed bovine serum albumin, 5 mM D-glucose and 0.3 mM L-[U- 14 C]-lysine or L-[1- 14 C]-leucine. The incorporation of carbon-14 into CO 2 and into 10% sulfosalicylic acid (SSA)-soluble and SSA-insoluble fractions of the incubation mixture was determined. Low (10mM) bicarbonate reduced the incorporation of lys and leu into protein but did not substantially affect the recovery of 14 CO 2 from either amino acid. High pH (7.7) resulted in reduced incorporation of lys and leu into protein, and decreased the oxidation of lys but not leu. The specific activity of lys (leu was not determined) in the SSA-soluble fraction was unaffected by bicarbonate or pH. The authors conclude that variations in extracellular pH and HCO 3 - (or pCO 2 ) affect the metabolism of amino acids by renal tubules and that low extracellular HCO 3 - (or pCO 2 ) may depress the incorporation of amino acids into protein

  6. A novel chemiluminescence method for determination of bisphenol Abased on the carbon dot-enhanced HCO3−–H2O2 system

    International Nuclear Information System (INIS)

    Amjadi, Mohammad; Manzoori, Jamshid L.; Hallaj, Tooba

    2015-01-01

    A simple and sensitive chemiluminescence (CL) method on the basis of carbon dot (C-dot) enhanced HCO 3 − –H 2 O 2 system, is designed for the determination of bisphenol A (BPA). The very weak CL of the HCO 3 − –H 2 O 2 system is enhanced by a factor of ∼100 in the presence of C-dots. Possible mechanisms that lead to the effect were elucidated by recording fluorescence and CL spectra and studying the effect of some radical scavengers. This enhancement is inhibited by BPA in the concentration range from 1.0 to 100 µg L −1 . This is exploited for its trace determination with a detection limit (3 s) of 0.3 µg L −1 . The established method was applied to the determination of BPA in baby bottle and water samples with satisfactory results. - Highlights: • The effect of carbon dots on HCO 3 − –H 2 O 2 chemiluminescence reaction is studied. • Carbon dots greatly enhance the CL signal of this reaction (∼100 fold). • The new CL system was applied to determination of bisphenol A in real samples

  7. Methodology to obtain exchange properties of the calcite surface-Application to major and trace elements: Ca(II), HCO3-, and Zn(II)

    International Nuclear Information System (INIS)

    Tertre, E.; Beaucaire, C.; Juery, A.; Ly, J.; Tertre, E.; Beaucaire, C.; Juery, A.; Ly, J.

    2010-01-01

    Sorption of inorganic elements onto carbonate minerals has been intensively described in the literature by two reaction steps: (1) a first one rapid and completed within a few hours and (2) a second one slower, eventually irreversible, and occurring at a constant rate. The first step is often attributed to an ion-exchange process, but its reversibility is rarely investigated. Consequently, discrimination of the global sorption phenomenon into two different mechanisms is not always justified. In this study, we investigated, by batch experiments, both sorption and desorption of Ca(II), HCO 3 - , and Zn(II), radiolabeled with isotopes 45 Ca(II), H 14 CO 3 - , and 65 Zn(II), respectively, onto synthetic pure calcite. Solutions were pre-equilibrated with atmospheric p(CO 2 ) and saturated with respect to calcite. Therefore, our purpose was to: (1) obtain experimental distribution coefficients of major elements (Ca(II) and HCO 3 - ) and a trace element (Zn(II)) onto calcite from sorption and desorption experiments, (2) test the validity of a first-occurring ion-exchange process generally noted in the literature, by calculating distribution coefficients for the 'sole' exchange process, and (3) quantify the amounts of Ca(II), HCO 3 - , and Zn(II) sorbed on the calcite surface by the sole 'exchange process' and compare them with surface crystallochemical data. Ca(II) or HCO 3 - sorption experimental data suggest that a significant fraction of these two elements was sorbed irreversibly onto or in the calcite. By using a method based on isotopic ratios, the Ca(II) or HCO 3 - concentrations, which are reversibly adsorbed on the calcite, have been quantified. These concentrations are respectively estimated at 4. 0 ± 2. 0 * 10 -4 and 7. 0 ± 1. 5 * 10 -4 mol/kg. The obtained Ca(II) surface concentration value is one order of magnitude lower than the one obtained from isotopic measurement by former authors [Geochim. Cosmochim. Acta 55 (1991) 1549; Geochim. Cosmochim. Acta 51

  8. Characterization of new polyol/H+ symporters in Debaryomyces hansenii.

    Directory of Open Access Journals (Sweden)

    Iliana Pereira

    Full Text Available Debaryomyces hansenii is a halotolerant yeast that produces and assimilates a wide variety of polyols. In this work we evaluate polyol transport in D. hansenii CBS 767, detecting the occurrence of polyol/H(+ (and sugar/H(+ symporter activity, through the transient extracellular alkalinization of unbuffered starved cell suspensions. From the D. hansenii genome database, we selected nine ORFs encoding putative transporter proteins to clone in a centromeric plasmid with C-terminal GFP tagging and screened for polyol/H(+ symporters by heterologous expression in Saccharomyces cerevisiae. Five distinct D. hansenii polyol/H(+ symporters were identified and characterized, with different specificities and affinities for polyols, namely one glycerol-specific (DhStl1, one D-galactitol-specific (DhSgl1, Symporter galactitol/H(+ 1, one D-(+-chiro-inositol-specific (DhSyi1, Symporter D-(+-chiro-inositol/H(+ 1, one for D-sorbitol/D-mannitol/ribitol/D-arabitol/D-galactitol (DhSyl1, Symporter Polyols 1 and another for D-sorbitol/D-mannitol/ribitol/D-arabitol (DhSyl2, Symporter Polyols 2. This work contributed to the annotation of new yeast polyol transporters, including two specific for uncommon substrates as galactitol and D-(+-chiro-inositol.

  9. Direct assessment of substrate binding to the Neurotransmitter:Sodium Symporter LeuT by solid state NMR

    DEFF Research Database (Denmark)

    Erlendsson, Simon; Gotfryd, Kamil; Larsen, Flemming Hofmann

    2017-01-01

    The Neurotransmitter:Sodium Symporters (NSSs) represent an important class of proteins mediating sodium-dependent uptake of neurotransmitters from the extracellular space. The substrate binding stoichiometry of the bacterial NSS protein, LeuT, and thus the principal transport mechanism, has been...

  10. Thermodynamic description of Tc(iv) solubility and carbonate complexation in alkaline NaHCO3-Na2CO3-NaCl systems.

    Science.gov (United States)

    Baumann, A; Yalçıntaş, E; Gaona, X; Polly, R; Dardenne, K; Prüßmann, T; Rothe, J; Altmaier, M; Geckeis, H

    2018-03-28

    The solubility of 99 Tc(iv) was investigated in dilute to concentrated carbonate solutions (0.01 M ≤ C tot ≤ 1.0 M, with C tot = [HCO 3 - ] + [CO 3 2- ]) under systematic variation of ionic strength (I = 0.3-5.0 M NaHCO 3 -Na 2 CO 3 -NaCl-NaOH) and pH m (-log[H + ] = 8.5-14.5). Strongly reducing conditions (pe + pH m ≈ 2) were set with Sn(ii). Carbonate enhances the solubility of Tc(iv) in alkaline conditions by up to 3.5 log 10 -units compared to carbonate-free systems. Solvent extraction and XANES confirmed that Tc was kept as +IV during the timeframe of the experiments (≤ 650 days). Solid phase characterization performed by XAFS, XRD, SEM-EDS, chemical analysis and TG-DTA confirmed that TcO 2 ·0.6H 2 O(am) controls the solubility of Tc(iv) under the conditions investigated. Slope analysis of the solubility data in combination with solid/aqueous phase characterization and DFT calculations indicate the predominance of the species Tc(OH) 3 CO 3 - at pH m ≤ 11 and C tot ≥ 0.01 M, for which thermodynamic and activity models are derived. Solubility data obtained above pH m ≈ 11 indicates the formation of previously unreported Tc(iv)-carbonate species, possibly Tc(OH) 4 CO 3 2- , although the likely formation of additional complexes prevents deriving a thermodynamic model valid for this pH m -region. This work provides the most comprehensive thermodynamic dataset available for the system Tc 4+ -Na + -Cl - -OH - -HCO 3 - -CO 3 2- -H 2 O(l) valid under a range of conditions relevant for nuclear waste disposal.

  11. Tolerance analysis of chloroplast OsCu/Zn-SOD overexpressing rice under NaCl and NaHCO3 stress.

    Directory of Open Access Journals (Sweden)

    Qingjie Guan

    Full Text Available The 636-bp-long cDNA sequence of OsCu/Zn-SOD (AK059841 was cloned from Oryza sativa var. Longjing11 via reverse transcription polymerase chain reaction (RT-PCR. The encoded protein comprised of 211 amino acids is highly homologous to Cu/Zn-SOD proteins from tuscacera rice and millet. Quantitative RT-PCR revealed that in rice, the level of OsCu/Zn-SOD gene expression was lowest in roots and was highest in petals and during the S5 leaf stage. Moreover, the expression level of OsCu/Zn-SOD gene expression decreased during the L5 leaf stage to maturity. The level of OsCu/Zn-SOD gene expression, however, was increased under saline-sodic stress and NaHCO3 stress. Germination tests under 125, 150, and 175 mM NaCl revealed that OsCu/Zn-SOD-overexpressing lines performed better than the non-transgenic (NT Longjing11 lines in terms of germination rate and height. Subjecting seedlings to NaHCO3 and water stress revealed that OsCu/Zn-SOD-overexpressing lines performed better than NT in terms of SOD activity, fresh weight, root length, and height. Under simulated NaHCO3 stress, OsCu/Zn-SOD-overexpressing lines performed better than NT in terms of survival rate (25.19% > 6.67% and yield traits (average grain weight 20.6 > 18.15 g. This study showed that OsCu/Zn-SOD gene overexpression increases the detoxification capacity of reactive oxygen species in O. sativa and reduces salt-induced oxidative damage. We also revealed the regulatory mechanism of OsCu/Zn-SOD enzyme in saline-sodic stress resistance in O. sativa. Moreover, we provided an experimental foundation for studying the mechanism of OsCu/Zn-SOD enzymes in the chloroplast.

  12. The Effects of Sodium Bicarbonate and Sodium Citrate on Blood pH, HCO3-, Lactate Metabolism and Time to Exhaustion

    Directory of Open Access Journals (Sweden)

    Soetanto Hartono

    2017-02-01

    Full Text Available The purpose of this study was to compare the effects of sodium bicarbonate and sodium citrate in increasing lactate concentration, blood pH, HCO3-, and time to exhaustion. Increased time to exhaustion is an advantage since the athletes can do more anaerobic work. Exhaustion could be delayed by increasing HCO3- to catch H+ produced by lactate metabolism to form H2O and CO2. The design of this research was randomized pretest posttest control group design. Thirty badminton student players were randomly selected and randomly assigned to three groups. The first group (the control group was given placebo, NaCl .9 g/dl, the second group was given sodium bicarbonate 300 mg/kg in 500 ml aqua, and the third group was given sodium citrate 300 mg/kg in 500 ml aqua. Blood pH and bicarbonate ion (HCO3- were measured through Opti Medical Blood gas Analyzer. Lactate was measured by Cobas Roche lactate Analyzer. Data was analyzed using Manova with .05 significant level. Blood pH of the groups taking sodium bicarbonate and sodium citrate were higher significantly against control group (p.05. Sodium bicarbonate is better than sodium citrate, although both were better than control (p<.05. Sodium bicarbonate is better than sodium citrate in increasing blood pH and time to exhaustion. The disadvantage of using sodium bicarbonate is that it can cause gastrointestinal problem and headache, so it is not advisable to be used by athletes who have the symptoms.

  13. Combinatorial effects of quercetin and sex-steroids on fluid and electrolytes' (Na+, Cl-, HCO3- secretory mechanisms in the uterus of ovariectomised female Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Huma Shahzad

    Full Text Available Dysregulation of uterine fluid environment could impair successful reproduction and this could be due to the effect of environmental estrogens. Therefore, in this study, effect of quercetin, an environmental estrogen on uterine fluid and electrolytes concentrations were investigated under sex-steroid influence. Ovariectomised adult female Sprague-Dawley rats were given 10, 50 or 100mg/kg/day quercetin subcutaneously with 17-β estradiol (E for seven days or three days E, then three days E plus progesterone (P (E+P treatment. Uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations were determined by in-vivo perfusion. Following sacrifice, uteri were harvested and levels of the proteins of interest were identified by Western blotting and Realtime PCR. Distribution of these proteins in the uterus was observed by immunofluorescence. Levels of uterine cAMP were measured by enzyme-linked immunoassay (EIA. Administration of quercetin at increasing doses increased uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations, but to the levels lesser than that of E. In concordant, levels of CFTR, SLC4A4, ENaC (α, β and γ, Na+/K+-ATPase, GPα/β, AC and cAMP in the uterus increased following increased in the doses of quercetin. Co-administration of quercetin with E caused uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations to decrease. In concordant, uterine CFTR, SLC26A6, SLC4A4, ENaC (α, β and γ, Na+/K+-ATPase, GPα/β, AC and cAMP decreased. Greatest effects were observed following co-administration of 10mg/kg/day quercetin with E. Co-administration of quercetin with E+P caused uterine fluid Na+ and HCO3- concentrations to increase but no changes in fluid secretion rate and Cl- concentration were observed. Co-administration of high dose quercetin (100 mg/kg/day with E+P caused uterine CFTR, SLC26A6, AC, GPα/β and ENaC (α, β and γ to increase. Quercetin-induced changes in the uterine fluid secretion rate and

  14. An in vitro study of urea, water, ion and CO2/HCO3- transport in the gastrointestinal tract of the dogfish shark (Squalus acanthias): the influence of feeding.

    Science.gov (United States)

    Liew, Hon Jung; De Boeck, Gudrun; Wood, Chris M

    2013-06-01

    In vitro gut sac preparations made from the cardiac stomach (stomach 1), pyloric stomach (stomach 2), intestine (spiral valve) and colon were used to examine the impact of feeding on transport processes in the gastrointestinal tract of the dogfish shark. Preparations were made from animals that were euthanized after 1-2 weeks of fasting, or at 24-48 h after voluntary feeding on a 3% ration of teleost fish (hake). Sacs were incubated under initially symmetrical conditions with dogfish saline on both surfaces. In comparison to an earlier in vivo study, the results confirmed that feeding caused increases in H(+) secretion in both stomach sections, but an increase in Cl(-) secretion only in stomach 2. Na(+) absorption, rather than Na(+) secretion, occurred in both stomach sections after feeding. All sections of the tract absorbed water and the intestine strongly absorbed Na(+) and Cl(-), regardless of feeding condition. The results also confirmed that feeding increased water absorption in the intestine (but not in the colon), and had little influence on the handling of Ca(2+) and Mg(2+), which exhibited negligible absorption across the tract. However, K(+) was secreted in the intestine in both fasted and fed preparations. Increased intestinal water absorption occurred despite net osmolyte secretion into the mucosal saline. The largest changes occurred in urea and CO2/HCO3(-) fluxes. In fasted preparations, urea was absorbed at a low rate in all sections except the intestine, where it was secreted. Instead of an increase in intestinal urea secretion predicted from in vivo data, feeding caused a marked switch to net urea absorption. This intestinal urea transport occurred at a rate comparable to urea reabsorption rates reported at gills and kidney, and was apparently active, establishing a large serosal-to-mucosal concentration gradient. Feeding also greatly increased intestinal CO2/HCO3(-) secretion; if interpreted as HCO3(-) transport, the rates were in the upper range

  15. Effect of NaHCO3 treatments on the activity of cell wall-degrading enzymes produced by Penicillium digitatum during the pathogenesis process on grapefruit.

    Science.gov (United States)

    Venditti, Tullio; D'hallewin, Guy; Ladu, Gianfranca; Petretto, Giacomo L; Pintore, Giorgio; Labavitch, John M

    2018-03-25

    The present study was performed to clarify the strategies of Penicillium digitatum during pathogenesis on citrus, assessing, on albedo plugs, the effects of treatment with NaHCO 3 , at two different pH (5 and 8.3), on cell wall-degrading enzymes activity, over a period of 72 h. The treatment with NaHCO 3 , under alkaline pH, delayed the polygalacturonase activity for 72 h, or 48 h in the case of the pectin lyase, if compared to the control or the same treatment at pH 5. On the contrary, the pectin methyl esterase activity rapidly increased after 24 h, in plugs dipped in the same solution. In this case, the activity remained higher than untreated or pH 5 treated plugs up to 72 h. The rapid increase in pectin methyl esterase activity, under alkaline conditions, is presumably the strategy of the pathogen to lower the pH, soon after the initiation of infection, in order to restore an optimal environment for the subsequent polygalacturonase and pectin lyase action. In fact at the same time, a low pH delayed the enzymatic activity of polygalacturonase and pectin lyase, the two enzymes that actually cleave the α-1,4-linkages between the galacturonic acid residues. This article is protected by copyright. All rights reserved.

  16. Studi Ketebalan Elektroda Pada Produksi Gas HHO (Hidrogen Hidrogen Oksigen Oleh Generator Hho Tipe Basah Dengan Katalis NaHCO3 (Natrium Bikarbonat

    Directory of Open Access Journals (Sweden)

    Ihsan Sopandi

    2015-12-01

    Full Text Available Abstrak. Salah satu energi alternatif yang efektif dikembangkan sekarang ini untuk mengganti bahan bakar minyak yaitu hidrogen. Untuk mendapatkan gas hidrogen dapat  dilakukan melalui proses elektrolisis air dengan memecahkan senyawa H2O menjadi gas HHO (Hidrogen Hidrogen Oksigen dengan bantuan listrik arus searah (Direct Current melalui media elektroda berupa plat stainless steel 304. Pada penelitian ini, akan diteliti hasil produksi gas HHO oleh generator HHO tipe basah dengan metode elektrolisa H2O menggunakan variasi ketebalan elektroda jenis stainless steel 304 yaitu 0,8 mm, 1 mm dan 1,2 mm dengan katalis NaHCO3 (Natrium Bikarbonat pada larutan elektrolitnya. Karakteristik yang diketahui meliputi konsumsi daya listrik yang digunakan oleh generator, volume gas yg dihasilkan,  laju produksi gas HHO yang dihasilkan dan efisiensi generator. Hasil penelitian dan pengujian generator HHO tipe basah ini didapatkan generator terbaik pada ketebalan elektroda 1 mm diperoleh data hasil pengujian dengan daya HHO yang digunakan sebesar 59,11 Watt, laju produksi gas HHO yang dihasilkan sebanyak 0,00054 kg/s dan efisiensi generator HHO sebesar 9,42 %.   Study On The  Electrode Thickness In HHO (Hidrogen Hidrogen Oksigen Gas Production By Wet Type HHO Generator With Catalyst NaHCO3 (Natrium Bikarbonat Abstract. One of the alternative energy that effective and currently being developed to replace fossil fuels is hydrogen. To obtain the hydrogen gas can be done through the process of electrolysis of water by breaking the compound H2O into HHO (Hydrogen Hydrogen Oxygen gas by using an electric direct current through the medium of 304 stainless steel plate  as an electrode. This research will be developing and observing HHO gas production process using HHO generator wet type (wet cell through electrolysis H2O with thickness variation of electrode that used 0.8 mm, 1 mm and 1.2 mm of electrode 304 stainless steel plate with NaHCO3 (Nathrium Bicarbonat

  17. A thermodynamic model for the solubility of NpO2(am) in the aqueous K+-HCO3--CO32--OH--H2O system

    International Nuclear Information System (INIS)

    Rai, D.; Hess, N.J.; Felmy, A.R.; Moore, D.A.; Yui, M.

    1999-01-01

    Solubility of NpO 2 (am) was determined in the aqueous K + -HCO 3 - -CO 3 2- -OH - -H 2 O system extending to high concentrations of carbonate, bicarbonate, and mixed carbonate-hydroxide. Several reducing agents (Fe powder, Na 2 S 2 O 4 , NH 2 . NH 2 , and NH 2 OH . HCl) were tested for their effectiveness to maintain neptunium in the tetravalent state. Of these reducing agents, Na 2 S 2 O 4 was found to be the most effective. Even in the presence of Na 2 S 2 O 4 , significant oxidation of Np(IV) to Np(V) occurred in samples containing relatively low concentrations of carbonate/bicarbonate, relatively high concentrations of hydroxide, and samples equilibrated for relatively long periods. X-ray absorption spectroscopy (XAS) and solvent extraction were used to identify aqueous species and oxidation states and to help select appropriate data sets for thermodynamic interpretations. The dominant aqueous species in CO 3 2- and relatively concentrated HCO 3 - solutions was found by XAS to be Np(CO 3 ) 5 6- . Solubility of NpO 2 (am) in carbonate and bicarbonate solutions increased dramatically with increasing molal concentrations (carbonate >0.1 moles per kg H 2 O (m) and bicarbonate >0.01 m), indicating that carbonate makes strong complexes with Np(IV). The dominant Np(IV)-carbonate species that reasonably described all of the experimental data were Np(CO 3 ) 5 6- in low to high concentrations of carbonate and hydroxide and in high concentrations of bicarbonate, and Np(OH) 2 (CO 3 ) 2 2- in low concentrations of bicarbonate. The logarithm of the thermodynamic equilibrium constants for the NpO 2 (am) dissolution reactions involving these species [(NpO 2 (am) + 5 CO 3 2- + 4 H + Np(CO 3 ) 3 6- + 2 H 2 O) and (NpO 2 (am) + 2 HCO 3 - Np(OH) 2 (CO 3 ) 2 2- )] were found to be 34.85 and -4.44, respectively. These values, when combined with the solubility product of NpO 2 (am) [log K Sp = -54.9 [1, and recent unpublished data from Rai et al.

  18. Monoclonal antibodies that bind the renal Na+/glucose symport system. 1. Identification

    International Nuclear Information System (INIS)

    Wu, J.S.R.; Lever, J.E.

    1987-01-01

    Phlorizin is a specific, high-affinity ligand that binds the active site of the Na + /glucose symporter by a Na + -dependent mechanism but is not itself transported across the membrane. The authors have isolated a panel of monoclonal antibodies that influence high-affinity, Na + -dependent phlorizin binding to pig renal brush border membranes. Antibodies were derived after immunization of mice either with highly purified renal brush border membranes or with apical membranes purified from LLC-PK 1 , a cell line of pig renal proximal tubule origin. Antibody 11A3D6, an IgG/sub 2b/, reproducibly stimulated Na + -dependent phlorizin binding whereas antibody 18H10B12, an IgM, strongly inhibited specific binding. These effects were maximal after 30-min incubation and exhibited saturation at increased antibody concentrations. Antibodies did not affect Na + -dependent sugar uptake in vesicles but significantly prevented transport inhibition by bound phlorizin. Antibodies recognized a 75-kDa antigen identified by Western blot analysis of brush border membranes, and a 75-kDa membrane protein could be immunoprecipitated by 18H10B12. These properties, provide compelling evidence that the 75-kDa antigen recognized by these antibodies is a component of the renal Na + /glucose symporter

  19. CO2 solubility in aqueous solutions containing Na+, Ca2+, Cl−, SO42− and HCO3-: The effects of electrostricted water and ion hydration thermodynamics

    International Nuclear Information System (INIS)

    Gilbert, Kimberly; Bennett, Philip C.; Wolfe, Will; Zhang, Tongwei; Romanak, Katherine D.

    2016-01-01

    Dissolution of CO 2 into deep subsurface brines for carbon sequestration is regarded as one of the few viable means of reducing the amount of CO 2 entering the atmosphere. Ions in solution partially control the amount of CO 2 that dissolves, but the mechanisms of the ion's influence are not clearly understood and thus CO 2 solubility is difficult to predict. In this study, CO 2 solubility was experimentally determined in water, NaCl, CaCl 2 , Na 2 SO 4, and NaHCO 3 solutions and a mixed brine similar to the Bravo Dome natural CO 2 reservoir; ionic strengths ranged up to 3.4 molal, temperatures to 140 °C, and CO 2 pressures to 35.5 MPa. Increasing ionic strength decreased CO 2 solubility for all solutions when the salt type remained unchanged, but ionic strength was a poor predictor of CO 2 solubility in solutions with different salts. A new equation was developed to use ion hydration number to calculate the concentration of electrostricted water molecules in solution. Dissolved CO 2 was strongly correlated (R 2  = 0.96) to electrostricted water concentration. Strong correlations were also identified between CO 2 solubility and hydration enthalpy and hydration entropy. These linear correlation equations predicted CO 2 solubility within 1% of the Bravo Dome brine and within 10% of two mixed brines from literature (a 10 wt % NaCl + KCl + CaCl 2 brine and a natural Na + , Ca 2+ , Cl − type brine with minor amounts of Mg 2+ , K + , Sr 2+ and Br − ). - Highlights: • Measured CO 2 solubility in Na + , Cl − , HCO 3 - , Ca 2+ and SO 4 2− solutions at high PCO 2 . • A new equation calculates electrostricted water (mol/kgw) from hydration number. • CO 2 solubility strongly correlates (R 2  = 0.96) to electrostricted water. • Ion electrostriction of water limits its availability for CO 2 caging and solvation. • Correlations predict CO 2 solubility of several mixed brines to within 1–9%.

  20. Thermodynamic modeling of neptunium(V) solubility in concentrated Na-CO3-HCO3-Cl-ClO4-H-OH-H2O systems

    International Nuclear Information System (INIS)

    Novak, C.F.; Roberts, K.E.

    1994-01-01

    Safety assessments of nuclear waste repositories often require estimation of actinide solubilities as a function of groundwater composition. Although considerable amount of research has been done on the solubility and speciation of actinides, relatively little has been done to unify these data into a model applicable to concentrate brines. Numerous authors report data on the aqueous chemical properties of Np(V) in NaClO 4 , Na 2 CO 3 , and NaCl media, but a consistent thermodynamic model for predicting these properties is not available. To meet this need, a model was developed to describe the solubility of Np(V) in Na-Cl-ClO 4 -CO 3 aqueous systems, based on the Pitzer activity coefficient formalism for concentrated electrolytes. Hydrolysis and/or carbonate complexation are the dominant aqueous reactions with neptunyl in these systems. Literature data for neptunyl extraction and solubility, and solubility data that the authors developed, are used to parameterize an integrated model for Np(V) solubility in the Np(V)-Na-CO 3 -HCO 3 -Cl-ClO 4 -H-OH-H 2 O system. The resulting model is tested against additional solubility data, and compared with Np(V) solubility experiments in complex synthetic brines

  1. Sequential application of NaHCO3, CaCl2 and Candida oleophila (isolate 13L) affects significantly Penicillum expansum growth and the infection degree in apples.

    Science.gov (United States)

    Molinu, M G; Pani, G; Venditti, T; Dore, A; Ladu, G; D'Hallewin, G

    2011-01-01

    The employment of biocontrol agents to restrain postharvest pathogens is an encouraging approach, although, efficacy and consistency are still below those of synthetic pesticides. Up to date, the 'integrated control strategy' seems to be the most promising way to overcome this gap. Here, we report the feasibility to control postharvest decay caused by Penicillium expansum in apples by a 2 min, single or sequential, immersion in water with an antagonistic yeast (Candida oleophila, isolate '13L'), 2% NaHCO3 (SBC) or 1% CaCl2. The treatments were carried out, on appels cv 'Miali' either un-wounded, wounded or wound-pathogen inoculated and then stored at 2 degrees C for 30 d followed by a 6 d simulated marketing period at 20 degrees C or alternatively stored only for 7 d at 20 degrees C. As a general role, the best results were attained when CaCl2 was applied with the yeast or when preceded by the SBC treatment. When the wounding and inoculation took place 24 h before the treatment, the latter application sequence of the two salts was three times more effective compared to the treatment with the sole antagonist, and one time when performed 24 h after the treatment. Interestingly, apples immersed in the sole 2% SBC solution had the highest percentage of decay during storage and when inoculated before moving to the simulated marketing period at 20 degrees C.

  2. Alpha-lipoic acid induces sodium iodide symporter expression in TPC-1 thyroid cancer cell line

    International Nuclear Information System (INIS)

    Choi, Hyun-Jeung; Kim, Tae Yong; Ruiz-Llorente, Sergio; Jeon, Min Ji; Han, Ji Min; Kim, Won Gu; Shong, Young Kee; Kim, Won Bae

    2012-01-01

    Introduction: Patients with metastatic thyroid cancers that do not uptake iodine need effective therapeutic option. Differentiation-inducing agents have been tried to restore functional expression of sodium iodide symporter (NIS) without success. Our objective was to assess the effect of alpha-lipoic acid (ALA), known as potential antioxidant, on expression of sodium iodide symporter in thyroid cancer cells. Methods: Human thyroid cancer-derived cell lines, TPC-1, were treated with ALA, and changes in NIS mRNA and protein expression were measured. ALA's effect on NIS gene promoter was evaluated, and functional NIS expression was assessed by iodide uptake assay. Results: Treatment with ALA increased NIS mRNA expression up to ten folds of control dose-dependently after 24 h of exposure. ALA increased NIS promoter activity, and increased iodide uptake by 1.6 fold. ALA induced expression of NIS protein, but had no significant effect on the plasma membrane trafficking. ALA increased phosphorylation of CREB and nuclear translocation of pCREB, and co-treatment of ALA and trichostatin A increased iodide uptake by three folds in TPC-1 cells. Conclusions: ALA is a potential agent to increase NIS transcription in TPC-1. It could be used as an adjunctive agent to increase efficacy of radioiodine therapy if combined with a strategy to increase NIS protein trafficking to cell membrane.

  3. Ingestion of Sodium Bicarbonate (NaHCO3) Following a Fatiguing Bout of Exercise Accelerates Postexercise Acid-Base Balance Recovery and Improves Subsequent High-Intensity Cycling Time to Exhaustion.

    Science.gov (United States)

    Gough, Lewis A; Rimmer, Steven; Osler, Callum J; Higgins, Matthew F

    2017-10-01

    This study evaluated the ingestion of sodium bicarbonate (NaHCO 3 ) on postexercise acid-base balance recovery kinetics and subsequent high-intensity cycling time to exhaustion. In a counterbalanced, crossover design, nine healthy and active males (age: 23 ± 2 years, height: 179 ± 5 cm, body mass: 74 ± 9 kg, peak mean minute power (W peak ) 256 ± 45 W, peak oxygen uptake (V̇O 2peak ) 46 ± 8 ml.kg -1 .min -1 ) performed a graded incremental exercise test, two familiarization and two experimental trials. Experimental trials consisted of cycling to volitional exhaustion (T LIM1 ) at 100% W PEAK on two occasions (T LIM1 and T LIM2 ) interspersed by a 90 min passive recovery period. Using a double-blind approach, 30 min into a 90 min recovery period participants ingested either 0.3 g.kg -1 body mass sodium bicarbonate (NaHCO 3 ) or a placebo (PLA) containing 0.1 g.kg -1 body mass sodium chloride (NaCl) mixed with 4 ml.kg -1 tap water and 1 ml.kg -1 orange squash. The mean differences between T LIM2 and T LIM1 was larger for PLA compared with NaHCO 3 (-53 ± 53 vs. -20 ± 48 s; p = .008, d = 0.7, CI =-0.3, 1.6), indicating superior subsequent exercise time to exhaustion following NaHCO 3 . Blood lactate [Bla - ] was similar between treatments post T LIM1 , but greater for NaHCO 3 post T LIM2 and 5 min post T LIM2 . Ingestion of NaHCO 3 induced marked increases (p < .01) in both blood pH (+0.07 ± 0.02, d = 2.6, CI = 1.2, 3.7) and bicarbonate ion concentration [HCO 3 - ] (+6.8 ± 1.6 mmo.l -1 , d = 3.4, CI = 1.8, 4.7) compared with the PLA treatment, before T LIM2 . It is likely both the acceleration of recovery, and the marked increases of acid-base after T LIM1 contributed to greater T LIM2 performance compared with the PLA condition.

  4. Role of Cl−–HCO3 − exchanger AE3 in intracellular pH homeostasis in cultured murine hippocampal neurons, and in crosstalk to adjacent astrocytes

    Science.gov (United States)

    Salameh, Ahlam I.; Hübner, Christian A.

    2016-01-01

    Key points A polymorphism of human AE3 is associated with idiopathic generalized epilepsy. Knockout of AE3 in mice lowers the threshold for triggering epileptic seizures. The explanations for these effects are elusive.Comparisons of cells from wild‐type vs. AE3–/– mice show that AE3 (present in hippocampal neurons, not astrocytes; mediates HCO3 – efflux) enhances intracellular pH (pHi) recovery (decrease) from alkali loads in neurons and, surprisingly, adjacent astrocytes.During metabolic acidosis (MAc), AE3 speeds initial acidification, but limits the extent of pHi decrease in neurons and astrocytes.AE3 speeds re‐alkalization after removal of MAc in neurons and astrocytes, and speeds neuronal pHi recovery from an ammonium prepulse‐induced acid load.We propose that neuronal AE3 indirectly increases acid extrusion in (a) neurons via Cl– loading, and (b) astrocytes by somehow enhancing NBCe1 (major acid extruder). The latter would enhance depolarization‐induced alkalinization of astrocytes, and extracellular acidification, and thereby reduce susceptibility to epileptic seizures. Abstract The anion exchanger AE3, expressed in hippocampal (HC) neurons but not astrocytes, contributes to intracellular pH (pHi) regulation by facilitating the exchange of extracellular Cl– for intracellular HCO3 –. The human AE3 polymorphism A867D is associated with idiopathic generalized epilepsy. Moreover, AE3 knockout (AE3–/–) mice are more susceptible to epileptic seizure. The mechanism of these effects has been unclear because the starting pHi in AE3–/– and wild‐type neurons is indistinguishable. The purpose of the present study was to use AE3–/– mice to investigate the role of AE3 in pHi homeostasis in HC neurons, co‐cultured with astrocytes. We find that the presence of AE3 increases the acidification rate constant during pHi recovery from intracellular alkaline loads imposed by reducing [CO2]. The presence of AE3 also speeds intracellular

  5. Role of Cl- -HCO3- exchanger AE3 in intracellular pH homeostasis in cultured murine hippocampal neurons, and in crosstalk to adjacent astrocytes.

    Science.gov (United States)

    Salameh, Ahlam I; Hübner, Christian A; Boron, Walter F

    2017-01-01

    A polymorphism of human AE3 is associated with idiopathic generalized epilepsy. Knockout of AE3 in mice lowers the threshold for triggering epileptic seizures. The explanations for these effects are elusive. Comparisons of cells from wild-type vs. AE3 -/- mice show that AE3 (present in hippocampal neurons, not astrocytes; mediates HCO 3 - efflux) enhances intracellular pH (pH i ) recovery (decrease) from alkali loads in neurons and, surprisingly, adjacent astrocytes. During metabolic acidosis (MAc), AE3 speeds initial acidification, but limits the extent of pH i decrease in neurons and astrocytes. AE3 speeds re-alkalization after removal of MAc in neurons and astrocytes, and speeds neuronal pH i recovery from an ammonium prepulse-induced acid load. We propose that neuronal AE3 indirectly increases acid extrusion in (a) neurons via Cl - loading, and (b) astrocytes by somehow enhancing NBCe1 (major acid extruder). The latter would enhance depolarization-induced alkalinization of astrocytes, and extracellular acidification, and thereby reduce susceptibility to epileptic seizures. The anion exchanger AE3, expressed in hippocampal (HC) neurons but not astrocytes, contributes to intracellular pH (pH i ) regulation by facilitating the exchange of extracellular Cl - for intracellular HCO 3 - . The human AE3 polymorphism A867D is associated with idiopathic generalized epilepsy. Moreover, AE3 knockout (AE3 -/- ) mice are more susceptible to epileptic seizure. The mechanism of these effects has been unclear because the starting pH i in AE3 -/- and wild-type neurons is indistinguishable. The purpose of the present study was to use AE3 -/- mice to investigate the role of AE3 in pH i homeostasis in HC neurons, co-cultured with astrocytes. We find that the presence of AE3 increases the acidification rate constant during pH i recovery from intracellular alkaline loads imposed by reducing [CO 2 ]. The presence of AE3 also speeds intracellular acidification during the early phase of

  6. Dynamic iodide trapping by tumor cells expressing the thyroidal sodium iodide symporter

    International Nuclear Information System (INIS)

    Dingli, David; Bergert, Elizabeth R.; Bajzer, Zeljko; O'Connor, Michael K.; Russell, Stephen J.; Morris, John C.

    2004-01-01

    The thyroidal sodium iodide symporter (NIS) in combination with various radioactive isotopes has shown promise as a therapeutic gene in various tumor models. Therapy depends on adequate retention of the isotope in the tumor. We hypothesized that in the absence of iodide organification, isotope trapping is a dynamic process either due to slow efflux or re-uptake of the isotope by cells expressing NIS. Iodide efflux is slower in ARH-77 and K-562 cells expressing NIS compared to a thyroid cell line. Isotope retention half times varied linearly with the number of cells expressing NIS. With sufficient NIS expression, iodide efflux is a zero-order process. Efflux kinetics in the presence or absence of perchlorate also supports the hypothesis that iodide re-uptake occurs and contributes to the retention of the isotope in tumor cells. Iodide organification was insignificant. In vivo studies in tumors composed of mixed cell populations confirmed these observations

  7. Carbonate mineral solubility at low temperatures in the Na-K-Mg-Ca-H-Cl-SO 4-OH-HCO 3-CO 3-CO 2-H 2O system

    Science.gov (United States)

    Marion, Giles M.

    2001-06-01

    Carbonate minerals have played an important role in the geochemical evolution of Earth, and may have also played an important role in the geochemical evolution of Mars and Europa. Several models have been published in recent years that describe chloride and sulfate mineral solubilities in concentrated brines using the Pitzer equations. Few of these models are parameterized for subzero temperatures, and those that are do not include carbonate chemistry. The objectives of this work are to estimate Pitzer-equation bicarbonate-carbonate parameters and carbonate mineral solubility products and to incorporate them into the FREZCHEM model to predict carbonate mineral solubilities in the Na-K-Mg-Ca-H-Cl-SO 4-OH-HCO 3-CO 3-CO 2-H 2O system at low temperatures (≤25°C) with a special focus on subzero temperatures. Most of the Pitzer-equation parameters and equilibrium constants are taken from the literature and extrapolated into the subzero temperature range. Solubility products for 14 sodium, potassium, magnesium, and calcium bicarbonate and carbonate minerals are included in the model. Most of the experimental data are at temperatures ≥ -8°C; only for the NaHCO 3-NaCl-H 2O and Na 2CO 3-NaCl-H 2O systems are there bicarbonate and carbonate data to temperatures as low as -21.6°C. In general, the fit of the model to the experimental data is good. For example, calculated eutectic temperatures and compositions for NaHCO 3, Na 2CO 3, and their mixtures with NaCl and Na 2SO 4 salts are in good agreement with experimental data to temperatures as low as -21.6°C. Application of the model to eight saline, alkaline carbonate waters give predicted pHs ranging from 9.2 to 10.2, in comparison with measured pHs that range from 8.7 to 10.2. The model suggests that the CaCO 3 mineral that precipitates during seawater freezing is probably calcite and not ikaite. The model demonstrates that a proposed salt assemblage for the icy surface of Europa consisting of highly hydrated MgSO 4

  8. Ni-based electrocatalyst for water oxidation developed In-situ in a HCO3 -/CO2 system at near-neutral pH

    KAUST Repository

    Joya, Khurram Saleem

    2014-03-10

    Electrochemically generated NiOx nanoworms from a neutral bicarbonate system split water into dioxygen and protons with tremendous efficiency and stability. The NiOx electrocatalyst follows a pH-potential dependence, revealing a PCET (proton coupled electron transfer) mechanism of one electron and one proton oxidation. It does not require proton abstracting phosphate or borate buffers for electrogeneration and catalysis, and shows promising activity for anodic oxidation of water in phosphate, borate, and carbonate buffers. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Ni-based electrocatalyst for water oxidation developed In-situ in a HCO3 -/CO2 system at near-neutral pH

    KAUST Repository

    Joya, Khurram Saleem; Joya, Yasir F.; De Groot, Huub J M

    2014-01-01

    Electrochemically generated NiOx nanoworms from a neutral bicarbonate system split water into dioxygen and protons with tremendous efficiency and stability. The NiOx electrocatalyst follows a pH-potential dependence, revealing a PCET (proton coupled electron transfer) mechanism of one electron and one proton oxidation. It does not require proton abstracting phosphate or borate buffers for electrogeneration and catalysis, and shows promising activity for anodic oxidation of water in phosphate, borate, and carbonate buffers. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. The sodium iodide symporter: its implications for imaging and therapy

    International Nuclear Information System (INIS)

    Spitzweg, C.

    2007-01-01

    The sodium iodide symporter (NIS) is an intrinsic plasma membrane glycoprotein that mediates the active transport of iodide in the thyroid gland and a number of extrathyroidal tissues, in particular lactating mammary gland. In addition to its key function in thyroid physiology, NIS-mediated iodide accumulation allows diagnostic thyroid scintigraphy as well as therapeutic radioiodine application in benign and malignant thyroid disease. NIS therefore represents one of the oldest targets for molecular imaging and therapy. Based on the effective administration of radioiodine that has been used for over 60 years in the management of follicular cell-derived thyroid cancer, cloning and characterization of the NIS gene has paved the way for the development of a novel cytoreductive gene therapy strategy based on targeted NIS expression in thyroidal and nonthyroidal cancer cells followed by therapeutic application of 131 I or alternative radionuclides, including 188 Re and 211 At. In addition, the possibility of direct and non-invasive imaging of functional NIS expression by 123 I- and 99m Tc-scintigraphy or 124 I-PET-imaging allows the application of NIS as a novel reporter gene. In conclusion, the dual role of NIS as diagnostic and therapeutic gene and the detection of extra-thyroidal endogenous NIS expression in breast cancer open promising perspectives in nuclear medicine and molecular oncology for diagnostic and therapeutic application of NIS outside the thyroid gland. (orig.)

  11. Penurunan Kromium (Cr dalam Limbah Cair Proses Penyamakan Kulit Menggunakan Senyawa Alkali Ca(OH2, NaOH, dan NaHCO3 (Studi Kasus di Pt Trimulyo Kencana Mas Semarang

    Directory of Open Access Journals (Sweden)

    Tri Joko

    2015-12-01

    Full Text Available ABTRACT Background : One of the industrial type which use hazardous materials in its production process is leather tanning industry, by using chromium compound (Cr. Chromium is a heavy metal compound which recognized has a high poison energy. Result of analysis of sampel industrial liquid waste of leather tanning of PT Trimulyo Kencana Mas (TKM Semarang showed that total chromium concervation was 49,575 m/l. This total Chromium rate was still above the standard quality of which enabled maximal 2,0 mg/l, according to Kep51/MENLH/110/1995. Alkali compound of Ca(OH2, NaOH and NaHC03 is chemicals able to be used for the processing of industrial liquid waste of pregnant leather tanning of chromium, functioning to boost up condensation pH andprecipitated chromium so that obtained chrome in theform of hydroxide chromium (Cr(OH3. Methods : which used in this research is (quasi experimental, with experiment variable repeated or referred as one group pretest ‑ posttest design. Results : of this research showed that optimum pH for the compound of each alkali at condition of pH 8, with the efficiency dissociation of chromium was equal to 99,28 % by using alkali compound of Ca(OH2 and of NaOH, while usage of NaHC03 equal to 98,50 %. Conclusions: Alkali compound of Ca(OH2, NaOH and NaHCO3 can degrade chromium concentration (Cr in liquid waste with high efficiency, that is reaching under standard quality. The most effective Compound of Alkali, evaluated from the technical aspect for the degradation of chromium concentration in liquid waste is NaOH, because with only small dose can dissociate chromium in liquid waste with high efficiency (99,28 %, For economic reason and recommendation for application in the field is Ca(OH2. Keyword : Efficiency Ca(OH2,, hydroxide chromium, NaHCO3, NaOH, pH, Chromium Compound

  12. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.

    LENUS (Irish Health Repository)

    Ryan, James

    2011-01-01

    The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro.

  13. Sodium iodide symporter: Its role in nuclear oncology

    International Nuclear Information System (INIS)

    Chung, June-Key

    2004-01-01

    Full text: Thyroid iodide uptake is basic to the clinical applications of radioiodine in diagnosis and therapy. Iodide uptake occurs across the membrane of thyroid follicular cells via an active transporter process mediated by the sodium/iodide symporter (NIS). The recent cloning of the gene encoding NIS enabled better characterization of the molecular mechanisms underlying the iodide transport, thus opening the way to clarify and expand its role in medicine. NIS contains 13 transmembrane segments, and its gene encodes a glycoprotein of 643 amino acids. Decreased NIS expression levels account for the reduced iodide uptake in thyroid carcinomas. We found that thyroid cancer patients with positive immunostaining for NIS responded to I-131 therapy better than did the patients with negative immunostaining. Thus, NIS gene can be used for radionuclide gene therapy. Targeted expression of functional NIS in cancer cells would enable these cells to concentrate iodide from plasma and would, therefore, offer the possibility of radioiodine therapy. We and others have shown that gene transfer of NIS into a variety of cell types confers increased radioiodine uptake up to several hundred-fold that of controls. There is great interest in exploring the possibility of NIS gene transfer to facilitate radioiodine therapy for non-thyroidal human cancers including hepatoma, prostate, breast, colon cancers as well as thyroid cancer. Recently, several approaches such as, targeted gene transfer, thyroid peroxidase gene co-transfection, retinoic acid treatment and Re-188 therapy instead of I-131, have been tried to improve this novel gene therapy. Imaging reporter gene is useful in non-invasively determining the location, duration and magnitude of transgene expression in living animal. Conventionally, HSV-tk and dopaminergic receptor (D2R) genes have been presented as possible imaging reporter genes. We proved that NIS could serve as an alternative imaging reporter gene. NIS has many

  14. Altered Regulation of type 3 Na+/H+ exchanger, type 1 Na+/HCO3- cotransporter, and Na+,K+-ATPase in the Kidney of Rats with Experimental Rhabdomyolysis

    Science.gov (United States)

    Ma, Seong Kwon; Bae, Eun Hui; Lee, JongUn; Kim, Sun Young; Kim, Sung Zoo; Choi, Ki Chul

    2007-01-01

    Metabolic acidosis was shown to correlate with deterioration of renal function in patients with rhabdomyolysis. The present study was aimed to investigate whether the changes of type 3 Na+/H+ exchanger (NHE3), type 1 Na+/HCO3- cotransporter (NBC1), and Na+,K+-ATPase α1 subunit may play a role in the pathogenesis of metabolic acidosis in glycerol-induced experimental rhabdomyolysis. Male Sprague-Dawley rats were deprived of fluid intake for 24 hours, and then were injected with 50% glycerol in normal saline (10 mL/kg, intramuscularly). At 24 hours after the glycerol injection, rats were sacrificed by decapitation. Control rats were injected with normal saline. The protein expression of NHE3, NBC1 and Na+,K+-ATPase α1 subunit was determined in the cortex of the kidney by immunoblotting and immunohistochemistry. Following the treatment of glycerol, creatinine clearance was significantly decreased, and high anion gap metabolic acidosis developed. In the experimental group, the expression of Na+,K+-ATPase α1 subunit was significantly decreased in the cortex of the kidney. On the contrary, the expression of NHE3 and NBC1 was significantly increased. Immunohistochemical analyses confirmed the immunoblotting data. In conclusion, the coordinate up-regulation of NHE3 and NBC1 may play an adaptive role against the metabolic acidosis in glycerol-induced rhabdomyolysis. PMID:24459502

  15. Linking loss of sodium-iodide symporter expression to DNA damage

    International Nuclear Information System (INIS)

    Lyckesvärd, Madeleine Nordén; Kapoor, Nirmal; Ingeson-Carlsson, Camilla; Carlsson, Therese; Karlsson, Jan-Olof; Postgård, Per; Himmelman, Jakob; Forssell-Aronsson, Eva; Hammarsten, Ola; Nilsson, Mikael

    2016-01-01

    Radiotherapy of thyroid cancer with I-131 is abrogated by inherent loss of radioiodine uptake due to loss of sodium iodide symporter (NIS) expression in poorly differentiated tumor cells. It is also known that ionizing radiation per se down-regulates NIS (the stunning effect), but the mechanism is unknown. Here we investigated whether loss of NIS-mediated iodide transport may be elicited by DNA damage. Calicheamicin, a fungal toxin that specifically cleaves double-stranded DNA, induced a full scale DNA damage response mediated by the ataxia-telangiectasia mutated (ATM) kinase in quiescent normal thyrocytes. At sublethal concentrations (<1 nM) calicheamicin blocked NIS mRNA expression and transepithelial iodide transport as stimulated by thyrotropin; loss of function occurred at a much faster rate than after I-131 irradiation. KU-55933, a selective ATM kinase inhibitor, partly rescued NIS expression and iodide transport in DNA-damaged cells. Prolonged ATM inhibition in healthy cells also repressed NIS-mediated iodide transport. ATM-dependent loss of iodide transport was counteracted by IGF-1. Together, these findings indicate that NIS, the major iodide transporter of the thyroid gland, is susceptible to DNA damage involving ATM-mediated mechanisms. This uncovers novel means of poor radioiodine uptake in thyroid cells subjected to extrinsic or intrinsic genotoxic stress. - Highlights: • DNA damage inhibits polarized iodide transport in normal thyroid cells. • Down-regulation of NIS expression is mediated by activation of the ATM kinase. • Long-term ATM inhibition also represses NIS-mediated iodide transport. • IGF-1 rescues NIS expression and iodide transport in DNA-damaged cells.

  16. Linking loss of sodium-iodide symporter expression to DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Lyckesvärd, Madeleine Nordén [Sahlgrenska Cancer Center, University of Gothenburg, Göteborg (Sweden); Department of Medical Chemistry and Cell Biology, University of Gothenburg, Göteborg (Sweden); Kapoor, Nirmal [Department of Medical Chemistry and Cell Biology, University of Gothenburg, Göteborg (Sweden); Ingeson-Carlsson, Camilla; Carlsson, Therese [Sahlgrenska Cancer Center, University of Gothenburg, Göteborg (Sweden); Department of Medical Chemistry and Cell Biology, University of Gothenburg, Göteborg (Sweden); Karlsson, Jan-Olof [Department of Medical Chemistry and Cell Biology, University of Gothenburg, Göteborg (Sweden); Postgård, Per; Himmelman, Jakob; Forssell-Aronsson, Eva [Department of Radiation Physics, University of Gothenburg, Göteborg (Sweden); Hammarsten, Ola [Department of Clinical Chemistry, University of Gothenburg, Göteborg (Sweden); Nilsson, Mikael, E-mail: mikael.nilsson@gu.se [Sahlgrenska Cancer Center, University of Gothenburg, Göteborg (Sweden); Department of Medical Chemistry and Cell Biology, University of Gothenburg, Göteborg (Sweden)

    2016-05-15

    Radiotherapy of thyroid cancer with I-131 is abrogated by inherent loss of radioiodine uptake due to loss of sodium iodide symporter (NIS) expression in poorly differentiated tumor cells. It is also known that ionizing radiation per se down-regulates NIS (the stunning effect), but the mechanism is unknown. Here we investigated whether loss of NIS-mediated iodide transport may be elicited by DNA damage. Calicheamicin, a fungal toxin that specifically cleaves double-stranded DNA, induced a full scale DNA damage response mediated by the ataxia-telangiectasia mutated (ATM) kinase in quiescent normal thyrocytes. At sublethal concentrations (<1 nM) calicheamicin blocked NIS mRNA expression and transepithelial iodide transport as stimulated by thyrotropin; loss of function occurred at a much faster rate than after I-131 irradiation. KU-55933, a selective ATM kinase inhibitor, partly rescued NIS expression and iodide transport in DNA-damaged cells. Prolonged ATM inhibition in healthy cells also repressed NIS-mediated iodide transport. ATM-dependent loss of iodide transport was counteracted by IGF-1. Together, these findings indicate that NIS, the major iodide transporter of the thyroid gland, is susceptible to DNA damage involving ATM-mediated mechanisms. This uncovers novel means of poor radioiodine uptake in thyroid cells subjected to extrinsic or intrinsic genotoxic stress. - Highlights: • DNA damage inhibits polarized iodide transport in normal thyroid cells. • Down-regulation of NIS expression is mediated by activation of the ATM kinase. • Long-term ATM inhibition also represses NIS-mediated iodide transport. • IGF-1 rescues NIS expression and iodide transport in DNA-damaged cells.

  17. Precipitation behaviors of Cs and Re(/Tc) by NaTPB and TPPCl from a simulated fission products-(Na2CO3-NaHCO3)-H2O2 solution

    International Nuclear Information System (INIS)

    Lee, Eil Hee; Lim, Jae Gwan; Chung, Dong Yong; Yang, Han Beum; Kim, Kwang Wook

    2010-01-01

    In this study, the removal of Cs and Tc from a simulated fission products (FP) solution which were co-dissolved with U during the oxidative-dissolution of spent fuel in a mixed carbonate solution of (Na 2 CO 3 -NaHCO 3 )-H 2 O 2 was investigated by using a selective precipitation method. As Cs and Tc might cause an unstable behavior due to the high decay heat emission of Cs as well as the fast migration of Tc when disposed of underground, it is one of the important issues to removal them in views of the increase of disposal safety. The precipitation of Cs and Re (as a surrogate for Tc) was examined by introducing sodium tetraphenylborate (NaTPB) and tetraphenylphosponium chloride (TPPCl), respectively. Precipitation of Cs by NaTPB and that of Re by TPPCl were completed within 5 minutes. Their precipitation rates were not influenced so much by the temperature and stirring speed even if they were increased by up to 50 .deg. C and 1,000 rpm. However, the pH of the solution was found to have a great influence on the precipitation with NaTPB and TPPCl. Since Mo tends to co-precipitate with Re at a lower pH, especially, it was effective that a selective precipitation of Re by TPPCl was carried out at pH of above 9 without co-precipitation of Mo and Re. Over 99% of Cs was precipitated when the ratio of [NaTPB]/[Cs]>1 and more than 99% of Re, likewise, was precipitated when the ratio of [TPPCl]/[Re]>1.

  18. Discovery of aryl-tri-fluoroborates as potent sodium/iodide sym-porter (NIS) inhibitors

    International Nuclear Information System (INIS)

    Lecat-Guillet, N.; Ambroise, Y.

    2008-01-01

    The structure-based design of sodium/iodide sym-porter (NIS) inhibitors identified new active compounds. The organo-tri-fluoroborate shown was found to inhibit iodide uptake with an IC50 value of 0.4 μM on rat-derived thyroid cells. The biological activity is rationalized by the presence of the BF3 - ion as a minimal binding motif for substrate recognition at the iodide binding site. (authors)

  19. Discovery of aryl-tri-fluoroborates as potent sodium/iodide sym-porter (NIS) inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lecat-Guillet, N.; Ambroise, Y. [CEA, DSV, Dept Bioorgan Chem and Isotop Labelling, Inst Biol and Technol, iBiTecS, F-91191 Gif Sur Yvette (France)

    2008-07-01

    The structure-based design of sodium/iodide sym-porter (NIS) inhibitors identified new active compounds. The organo-tri-fluoroborate shown was found to inhibit iodide uptake with an IC50 value of 0.4 {mu}M on rat-derived thyroid cells. The biological activity is rationalized by the presence of the BF3{sup -} ion as a minimal binding motif for substrate recognition at the iodide binding site. (authors)

  20. Substrate-Na{sup +} complex formation: Coupling mechanism for {gamma}-aminobutyrate symporters

    Energy Technology Data Exchange (ETDEWEB)

    Pallo, Anna; Simon, Agnes [Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences (Hungary); Bencsura, Akos [Department of Theoretical Chemistry, Institute of Structural Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest (Hungary); Heja, Laszlo [Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences (Hungary); Kardos, Julianna, E-mail: jkardos@chemres.hu [Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences (Hungary)

    2009-07-24

    Crystal structures of transmembrane transport proteins belonging to the important families of neurotransmitter-sodium symporters reveal how they transport neurotransmitters across membranes. Substrate-induced structural conformations of gated neurotransmitter-sodium symporters have been in the focus of research, however, a key question concerning the mechanism of Na{sup +} ion coupling remained unanswered. Homology models of human glial transporter subtypes of the major inhibitory neurotransmitter {gamma}-aminobutyric acid were built. In accordance with selectivity data for subtype 2 vs. 3, docking and molecular dynamics calculations suggest similar orthosteric substrate (inhibitor) conformations and binding crevices but distinguishable allosteric Zn{sup 2+} ion binding motifs. Considering the occluded conformational states of glial human {gamma}-aminobutyric acid transporter subtypes, we found major semi-extended and minor ring-like conformations of zwitterionic {gamma}-aminobutyric acid in complex with Na{sup +} ion. The existence of the minor ring-like conformation of {gamma}-aminobutyric acid in complex with Na{sup +} ion may be attributed to the strengthening of the intramolecular H-bond by the electrostatic effect of Na{sup +} ion. Coupling substrate uptake into cells with the thermodynamically favorable Na{sup +} ion movement through substrate-Na{sup +} ion complex formation may be a mechanistic principle featuring transmembrane neurotransmitter-sodium symporter proteins.

  1. Genetically targeted radiotherapy using the sodium-iodide symporter for treatment of head and neck cancer

    International Nuclear Information System (INIS)

    Gaut, A.W.; Niu, G.; Graham, M.M.; Domann, F.E.; Krager, K.J.

    2003-01-01

    Attempts at using gene therapy for cancer treatment have achieved limited success. Traditional in vivo gene therapy techniques are limited by relatively inefficient gene transfer, with only a small fraction of tumor cells transfected with the gene of interest. Gene therapy strategies yielding substantial bystander cytotoxicity are preferable and could yield significant clinical effect despite a lack of gene transfer to the entire tumor. We report the successful use of such a strategy in head and neck squamous cell carcinoma (HNSCC) cell lines. The sodium iodide symporter (NIS) gene, expressed primarily in the thyroid, is responsible for physiologic iodide accumulation. Expression of NIS in non-thyroid cell lines has been shown to confer iodide-concentrating ability. Using a recombinant adenovirus-NIS construct (Ad-NIS) delivered to HNSCC cell lines, we demonstrate radioiodide accumulation 15- to 30-fold higher than that of cell lines transduced with a control (Ad-Bgl II) adenovirus. Consistent with NIS-mediated uptake, this accumulation is inhibited by treatment with perchlorate. Using a clonogenic cell survival assay, we demonstrate a statistically significant, dose-dependent decrease in cell survival after delivery of Ad-NIS followed by administration of varying doses of I-131. Compared to a control, Ad-Bgl II-treated group, absolute survival was reduced by 80% at the highest dose of I-131 in Ad-NIS-treated cells. We also demonstrate the ability of NIS gene transfer followed by systemic administration of I-131 to dramatically attenuate tumor formation in nude mice. Three weeks after subcutaneous injection of tumor cells, tumors treated with Ad-NIS had decreased in size by 0.7±0.1 mm, whereas control tumors treated with Ad-Bgl II had increased in size by 7.4±1.7 mm. The relative accessibility of head and neck cancers make them attractive targets for gene therapy. Our data demonstrate the feasibility of genetically targeted radiotherapy using the NIS gene as a

  2. Radiostatine and radioiodine uptake characterization in sodium iodine symporter-expressing cell lines

    International Nuclear Information System (INIS)

    Petrich, T.; Helmeke, H.J.; Meyer, G.J.; Knapp, W.H.; Poetter, E.

    2002-01-01

    Full text: The sodium iodide symporter (NIS) has been recognized as an attractive target for cancer gene therapy. Here we investigated NIS-mediated transport of the high LET α-emitter astatine, 211 At, in comparison to radioiodine. A constitutive expression vector harbouring the human NIS cDNA was used in combination with reporter gene vectors for transient transfection of 13 different human cancer cell lines. Radioiodine uptake was measured as well as transfection efficiencies. Six stable NIS-expressing cell lines (3 derived from thyroid carcinomas, 2 colon carcinoma, 1 glioblastoma) were generated by antibiotic selection. NIS expression was monitored by immunohistochemistry and RT-PCR. Subsequently the radioastatine and radioiodine uptake characteristics of genetically modified cells were studied in comparison to the respective control cells. After xenotransplantation in nude mice in vivo tumor imaging by scintigraphy and biodistribution studies following organ removal were performed. Transient transfection of NIS cDNA led to high specific sodium perchlorate-sensitive radioiodine uptake in NIS-expressing cells that roughly correlates to transfection efficiencies. Similarly, stable NIS-expressing cell lines were able to concentrate high levels of radioiodine and in addition showed comparable transport capacity for radioastatine. Accumulation of 211 At was inhibited by sodium perchlorate like iodide uptake and displayed dependency an extracellular Na + - and I - -ions as well. Compared to wash-out experiments in cell culture the effective half life of radioiodine and radioastatine in vivo was significantly prolonged. Preliminary dose calculations by MIRD concepts indicated higher tumor radiation doses for 211 At compared to 131 I. Tumor cells of different origins transfected with the NIS-expression vector specifically and significantly take-up radioiodine and radioastatine in vitro and in vivo. The data provide direct evidence that the NIS efficiently transports

  3. In Vivo Imaging of Retinoic Acid Receptor Activity using a Sodium/Iodide Symporter and Luciferase Dual Imaging Reporter Gene

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    Min Kyung So

    2004-07-01

    Full Text Available Retinoic acids are natural derivatives of vitamin A, and play important roles in modulating tumor cell growth by regulating differentiation, thus suggesting the potential use of these derivatives in cancer therapy and prevention. To visualize the intranuclear responses of functional retinoic acid receptors, we have developed a dual-imaging reporter gene system based on the use of sodium/iodide symporter (NIS and luciferase in cancer cell lines. NIS and luciferase genes were linked with an internal ribosome entry site, and placed under the control of an artificial cis-acting retinoic acid responsive element (pRARE/NL. After retinoic acid treatment, I-125 uptake by pRARE/NL transfected cells was found to have increased by up to about five times that of nontreated cells. The bioluminescence intensity of pRARE/NL transfected cells showed dose-dependency. In vivo luciferase images showed higher intensity in retinoic acid treated SK-RARE/NL tumors, and scintigraphic images of SK-RARE/NL tumors showed increased Tc-99m uptake after retinoic acid treatment. The NIS/luciferase imaging reporter system was sufficiently sensitive to allow the visualization of intranuclear retinoic acid receptor activity. This cis-enhancer imaging reporter system may be useful in vitro and in vivo for the evaluation of retinoic acid responses in such areas as cellular differentiation and chemoprevention.

  4. Rhenium-188 as an alternative to Iodine-131 for treatment of breast tumors expressing the sodium/iodide symporter (NIS)

    International Nuclear Information System (INIS)

    Dadachova, E.; Bouzahzah, B.; Zuckier, L.S.; Pestell, R.G.

    2002-01-01

    The sodium-iodide symporter (NIS), which transports iodine into the cell, is expressed in thyroid tissue and was recently found to be expressed in approximately 80% of human breast cancers but not in healthy breast tissue. These findings raised the possibility that therapeutics targeting uptake by NIS may be used for breast cancer treatment. To increase the efficacy of such therapy it would be ideal to identify a radioactive therapy with enhanced local emission. The feasibility of using the powerful beta-emitting radiometal 188 Re in the form of 188 Re-perrhenate was therefore compared with 131 I for treatment of NIS-expressing mammary tumors. In the current studies, using a xenografted breast cancer model induced by the ErbB2 oncogene in nude mice, 188 Re-perrhenate exhibited NIS-dependent uptake into the mammary tumor. Dosimetry calculations in the mammary tumor demonstrate that 188 Re-perrhenate is able to deliver a dose 4.5 times higher than 131 I suggesting it may provide enhanced therapeutic efficacy

  5. Sodium bicarbonate causes dose-dependent increases in cerebral blood flow in infants and children with single ventricle physiology

    Science.gov (United States)

    Buckley, Erin M.; Naim, Maryam Y.; Lynch, Jennifer M.; Goff, Donna A.; Schwab, Peter J.; Diaz, Laura K.; Nicolson, Susan C.; Montenegro, Lisa M.; Lavin, Natasha A.; Durduran, Turgut; Spray, Thomas L.; Gaynor, J. William; Putt, Mary E.; Yodh, A.G.; Fogel, Mark A.; Licht, Daniel J.

    2013-01-01

    Background Sodium bicarbonate (NaHCO3) is a common treatment for metabolic acidemia, however little definitive information exists regarding its treatment efficacy and cerebral hemodynamic effects. This pilot observational study quantifies relative changes in cerebral blood flow (rCBF) and oxy and deoxy-hemoglobin concentrations (ΔHbO2 and ΔHb) due to bolus administration of NaHCO3 in patients with mild base deficits. Methods Infants and children with hypoplastic left heart syndrome (HLHS) were recruited prior to cardiac surgery. NaHCO3 was given as needed for treatment of base deficit. Diffuse optical spectroscopies were employed for 15 minutes post-injection to non-invasively monitor ΔHb, ΔHbO2 and rCBF relative to baseline prior to NaHCO3 administration. Results Twenty-two anesthetized and mechanically ventilated HLHS patients (1 day to 4 years old) received a median (interquartile range) dose of 1.1 (0.8, 1.8) mEq/kg NaHCO3 administered intravenously over 10–20 seconds to treat a base deficit of −4 (−6, −3) mEq/l. NaHCO3 caused significant dose-dependent increases in rCBF, however population averaged ΔHb or Δ4HbO2 compared to controls were not significant. Conclusions Dose-dependent increases in cerebral blood flow (CBF) caused by bolus NaHCO3 are an important consideration in vulnerable populations wherein risk of rapid CBF fluctuations does not outweigh the benefit of treating a base deficit. PMID:23403802

  6. CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors.

    Science.gov (United States)

    Le Floch, Renaud; Chiche, Johanna; Marchiq, Ibtissam; Naiken, Tanesha; Naïken, Tanesha; Ilc, Karine; Ilk, Karine; Murray, Clare M; Critchlow, Susan E; Roux, Danièle; Simon, Marie-Pierre; Pouysségur, Jacques

    2011-10-04

    Malignant tumors exhibit increased dependence on glycolysis, resulting in abundant export of lactic acid, a hypothesized key step in tumorigenesis. Lactic acid is mainly transported by two H(+)/lactate symporters, MCT1/MCT4, that require the ancillary protein CD147/Basigin for their functionality. First, we showed that blocking MCT1/2 in Ras-transformed fibroblasts with AR-C155858 suppressed lactate export, glycolysis, and tumor growth, whereas ectopic expression of MCT4 in these cells conferred resistance to MCT1/2 inhibition and reestablished tumorigenicty. A mutant-derivative, deficient in respiration (res(-)) and exclusively relying on glycolysis for energy, displayed low tumorigenicity. These res(-) cells could develop resistance to MCT1/2 inhibition and became highly tumorigenic by reactivating their endogenous mct4 gene, highlighting that MCT4, the hypoxia-inducible and tumor-associated lactate/H(+) symporter, drives tumorigenicity. Second, in the human colon adenocarcinoma cell line (LS174T), we showed that combined silencing of MCT1/MCT4 via inducible shRNA, or silencing of CD147/Basigin alone, significantly reduced glycolytic flux and tumor growth. However, both silencing approaches, which reduced tumor growth, displayed a low level of CD147/Basigin, a multifunctional protumoral protein. To gain insight into CD147/Basigin function, we designed experiments, via zinc finger nuclease-mediated mct4 and basigin knockouts, to uncouple MCTs from Basigin expression. Inhibition of MCT1 in MCT4-null, Basigin(high) cells suppressed tumor growth. Conversely, in Basigin-null cells, in which MCT activity had been maintained, tumorigenicity was not affected. Collectively, these findings highlight that the major protumoral action of CD147/Basigin is to control the energetics of glycolytic tumors via MCT1/MCT4 activity and that blocking lactic acid export provides an efficient anticancer strategy.

  7. ZrFsy1, a high-affinity fructose/H+ symporter from fructophilic yeast Zygosaccharomyces rouxii.

    Directory of Open Access Journals (Sweden)

    Maria José Leandro

    Full Text Available Zygosaccharomyces rouxii is a fructophilic yeast than can grow at very high sugar concentrations. We have identified an ORF encoding a putative fructose/H(+ symporter in the Z. rouxii CBS 732 genome database. Heterologous expression of this ORF in a S. cerevisiae strain lacking its own hexose transporters (hxt-null and subsequent kinetic characterization of its sugar transport activity showed it is a high-affinity low-capacity fructose/H(+ symporter, with Km 0.45 ± 0.07 mM and Vmax 0.57 ± 0.02 mmol h(-1 (gdw(-1. We named it ZrFsy1. This protein also weakly transports xylitol and sorbose, but not glucose or other hexoses. The expression of ZrFSY1 in Z. rouxii is higher when the cells are cultivated at extremely low fructose concentrations (<0.2% and on non-fermentable carbon sources such as mannitol and xylitol, where the cells have a prolonged lag phase, longer duplication times and change their microscopic morphology. A clear phenotype was determined for the first time for the deletion of a fructose/H(+ symporter in the genome where it occurs naturally. The effect of the deletion of ZrFSY1 in Z. rouxii cells is only evident when the cells are cultivated at very low fructose concentrations, when the ZrFsy1 fructose symporter is the main active fructose transporter system.

  8. Evaluation of transcriptional activity of the oestrogen receptor with sodium iodide symporter as an imaging reporter gene.

    Science.gov (United States)

    Kang, Joo Hyun; Chung, June-Key; Lee, Yong Jin; Kim, Kwang Il; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul

    2006-10-01

    Oestrogen receptors are ligand-dependent transcription factors whose activity is modulated either by oestrogens or by an alternative signalling pathway. Oestrogen receptors interact via a specific DNA-binding domain, the oestrogen responsive element (ERE), in the promoter region of sensitive genes. This binding leads to an initiation of gene expression and hormonal effects. To determine the transcriptional activity of the oestrogen receptor, we developed a molecular imaging system using sodium iodide symporter (NIS) as a reporter gene. The NIS reporter gene was placed under the control of an artificial ERE derived from pERE-TA-SEAP and named as pERE-NIS. pERE-NIS was transferred to MCF-7, human breast cancer cells, which highly expressed oestrogen receptor-alpha with lipofectamine. Stably expressing cells were generated by selection with G418 for 14 days. After treatment of 17beta-oestradiol and tamoxifen with serial doses, the (125)I uptake was measured for the determination of NIS expression. The inhibition of NIS activity was performed with 50 micromol x l(-1) potassium perchlorate. The MCF7/pERE-NIS treated with 17beta-oestradiol accumulated (125)I up to 70-80% higher than did non-treated cells. NIS expression was increased according to increasing doses of 17beta-oestradiol. MCF7/pERE-NIS treated with tamoxifen also accumulated (125)I up to 50% higher than did non-treated cells. Potassium perchlorate completely inhibited (125)I uptake. When MDA-MB231 cells, the oestrogen receptor-negative breast cancer cells, were transfected with pERE-NIS, (125)I uptake of MDA-MB-231/pERE-NIS did not increase. This pERE-NIS reporter system is sufficiently sensitive for monitoring transcriptional activity of the oestrogen receptor. Therefore, cis-enhancer reporter systems with ERE will be applicable to the development of a novel selective oestrogen receptor modulator with low toxicity and high efficacy.

  9. The mitigating effect of calcification-dependent of utilization of inorganic carbon of Chara vulgaris Linn on NH4-N toxicity.

    Science.gov (United States)

    Wang, Heyun; Ni, Leyi; Xie, Ping

    2013-09-01

    Increased ammonium (NH4-N) concentrations in water bodies have been reported to adversely affect the dominant species of submersed vegetation in meso-eutrophic waters worldwide. However calcareous plants were lowly sensitive to NH4-N toxicity. In order to make clear the function of calcification in the tolerance of calcareous plants to NH4-N stress, we studied the effects of increased HCO3(-) and additional NH4-N on calcification and utilization of dissolve inorganic carbon (DIC) in Chara vulgaris Linn in a 7-d sub-acute experiment (light:dark 12:12h) carried out in an open experimental system in lab. Results revealed that calcification was dependent of utilization of dissolve inorganic carbon. Additional HCO3(-) significantly decreased the increase of pH while additional NH4-N did not. And additional HCO3(-) significantly improved calcification while NH4-N did in versus in relation to the variation of DIC concentration. However, addition of both HCO3(-) and NH4-N increased utilization of DIC. This resulted in calcification to utilization of DIC ratio decreased under additional NH4-N condition while increased under additional HCO3(-) conditions in response to the variation of solution pH. In the present study, external HCO3(-) decreased the increase of solution pH by increasing calcification, which correspondingly mitigated the toxic effect of high NH4-N. And we argue that the mitigating effect of increased HCO3(-) on NH4-N toxicity is dependent of plant calcification, and it is a positive feedback mechanism, potentially leading to the dominance of calcareous plants in meso-eutrophic water bodies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. The iodide sym-porter (NIS): new perspectives in nuclear oncology

    International Nuclear Information System (INIS)

    Pourcher, Th.; Lindenthal, S.; Basquin, C.; Ferhat, O.; Marsault, R.; Carrier, P.; Koulibaly, M.; Bussiere, F.; Darcourt, J.

    2005-01-01

    The sodium iodide sym-porter (NIS) is the plasma membrane protein that mediates uptake of iodide in the thyroid and other organs such as the stomach and the salivary gland. The cloning of its cDNA allows the targeting of NIS expression into any cell using gene therapy. This enables iodide uptake and thus NIS can be used as reporter imaging for live animals. More intriguingly, this new technique has potential using radio-iodide therapy to selectively destroy tumour cells. These two approaches employ common techniques in nuclear medicine. Many experiments on cultured cells and on animals have been carried out; they established clearly the advantages of this genetically targeted radiotherapy. Recent studies employing this therapy on multiple myeloma cell lines implanted in mice or on hepato-carcinoma-bearing rats, resulted in important tumour remission. However, additional studies on NIS regulation and the use of alternative radioisotopes transported by NIS are required to further develop this promising approach. (author)

  11. Small-molecule inhibitors of sodium iodide sym-porter function

    International Nuclear Information System (INIS)

    Lecat-Guillet, N.; Merer, G.; Lopez, R.; Rousseau, B.; Ambroise, Y.; Pourcher, T.

    2008-01-01

    The Na + /l - sym-porter (NIS) mediates iodide uptake into thyroid follicular cells. Although NIS has been cloned and thoroughly studied at the molecular level, the biochemical processes involved in post-translational regulation of NIS are still unknown. The purpose of this study was to identify and characterize inhibitors of NIS function. These small organic molecules represent a starting point in the identification of pharmacological tools for the characterization of NIS trafficking and activation mechanisms. screening of a collection of 17020 drug-like compounds revealed new chemical inhibitors with potencies down to 40 nM. Fluorescence measurement of membrane potential indicates that these inhibitors do not act by disrupting the sodium gradient. They allow immediate and total iodide discharge from preloaded cells in accord with a specific modification of NIS activity, probably through distinct mechanisms. (authors)

  12. Small-molecule inhibitors of sodium iodide sym-porter function

    Energy Technology Data Exchange (ETDEWEB)

    Lecat-Guillet, N.; Merer, G.; Lopez, R.; Rousseau, B.; Ambroise, Y. [CEA, DSV, Dept Bioorgan Chem et Isotop Labelling, Inst Biol et Biotechnol iBiTecS, F-91191 Gif Sur Yvette (France); Pourcher, T. [Univ Nice Sophia Antipolis, Dept Biochem et Nucl Toxicol, F-06107 Nice (France)

    2008-07-01

    The Na{sup +}/l{sup -} sym-porter (NIS) mediates iodide uptake into thyroid follicular cells. Although NIS has been cloned and thoroughly studied at the molecular level, the biochemical processes involved in post-translational regulation of NIS are still unknown. The purpose of this study was to identify and characterize inhibitors of NIS function. These small organic molecules represent a starting point in the identification of pharmacological tools for the characterization of NIS trafficking and activation mechanisms. screening of a collection of 17020 drug-like compounds revealed new chemical inhibitors with potencies down to 40 nM. Fluorescence measurement of membrane potential indicates that these inhibitors do not act by disrupting the sodium gradient. They allow immediate and total iodide discharge from preloaded cells in accord with a specific modification of NIS activity, probably through distinct mechanisms. (authors)

  13. Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.

    Directory of Open Access Journals (Sweden)

    Dana Haddad

    Full Text Available INTRODUCTION: Oncolytic viruses show promise for treating cancer. However, to assess therapy and potential toxicity, a noninvasive imaging modality is needed. This study aims to determine the in vivo biodistribution, and imaging and timing characteristics of a vaccinia virus, GLV-1h153, encoding the human sodium iodide symporter (hNIS. METHODS: GLV-1h153 was modified from GLV-1h68 to encode the hNIS gene. Timing of cellular uptake of radioiodide (131I in human pancreatic carcinoma cells PANC-1 was assessed using radiouptake assays. Viral biodistribution was determined in nude mice bearing PANC-1 xenografts, and infection in tumors confirmed histologically and optically via Green Fluorescent Protein (GFP and bioluminescence. Timing characteristics of enhanced radiouptake in xenografts were assessed via (124I-positron emission tomography (PET. Detection of systemic administration of virus was investigated with both (124I-PET and 99m-technecium gamma-scintigraphy. RESULTS: GLV-1h153 successfully facilitated time-dependent intracellular uptake of (131I in PANC-1 cells with a maximum uptake at 24 hours postinfection (P<0.05. In vivo, biodistribution profiles revealed persistence of virus in tumors 5 weeks postinjection at 10(9 plaque-forming unit (PFU/gm tissue, with the virus mainly cleared from all other major organs. Tumor infection by GLV-1h153 was confirmed via optical imaging and histology. GLV-1h153 facilitated imaging virus replication in tumors via PET even at 8 hours post radiotracer injection, with a mean %ID/gm of 3.82 ± 0.46 (P<0.05 2 days after intratumoral administration of virus, confirmed via tissue radiouptake assays. One week post systemic administration, GLV-1h153-infected tumors were detected via (124I-PET and 99m-technecium-scintigraphy. CONCLUSION: GLV-1h153 is a promising oncolytic agent against pancreatic cancer with a promising biosafety profile. GLV-1h153 facilitated time-dependent hNIS-specific radiouptake in pancreatic

  14. Sodium iodide symporter (NIS) in extrathyroidal malignancies: focus on breast and urological cancer

    International Nuclear Information System (INIS)

    Micali, Salvatore; Bulotta, Stefania; Puppin, Cinzia; Territo, Angelo; Navarra, Michele; Bianchi, Giampaolo; Damante, Giuseppe; Filetti, Sebastiano; Russo, Diego

    2014-01-01

    Expression and function of sodium iodide symporter (NIS) is requisite for efficient iodide transport in thyrocytes, and its presence in cancer cells allows the use of radioiodine as a diagnostic and therapeutic tool in thyroid neoplasia. Discovery of NIS expression in extrathyroidal tissues, including transformed cells, has opened a novel field of research regarding NIS-expressing extrathyroidal neoplasia. Indeed, expression of NIS may be used as a biomarker for diagnostic, prognostic, and therapeutic purposes. Moreover, stimulation of endogenous NIS expression may permit the radioiodine treatment of extrathyroidal lesions by concentrating this radioisotope. This review describes recent findings in NIS research in extrathyroidal malignancies, focusing on breast and urological cancer, emphasizing the most relevant developments that may have clinical impact. Given the recent progress in the study of NIS regulation as molecular basis for new therapeutic approaches in extrathyroidal cancers, particular attention is given to studies regarding the relationship between NIS and clinical-pathological aspects of the tumors and the regulation of NIS expression in the experimental models

  15. Human sodium iodide symporter (hNIS) in fibroadenoma breast--a immunohistochemical study.

    Science.gov (United States)

    Rai, Ruchi; Shrivastava, Ashutosh; Tandon, Ashwani; Godbole, Madan M; Kumar, Sandeep; Das, Vinita; Dwivedi, Varsha; Pal, Lily

    2011-02-01

    Human sodium iodide symporter (hNIS), responsible for the active transport of iodine is an integral plasma membrane glycoprotein present in the thyroid cells and extrathyroid tissues like breast and salivary glands. If its functional form is unequivocally shown in benign or malignant breast tissues, then it may serve as a basis for diagnosis and treatment using radioactive iodine. With an aim to analyze the hNIS expression in a distinct benign breast condition of fibroadenoma, biopsy proven fibroadenoma tissues, normal non-lactating breast tissue and biopsy proven infiltrating duct carcinoma tissues were examined for hNIS expression using immunohistochemistry. Out of 20 biopsy proven fibroadenoma tissues, 19 (95%) showed positivity for hNIS protein and only one was negative. Of these 10% were mildly positive, 50% cases were moderately positive and 35% showed intense positivity. None of the control tissue obtained from reduction mammoplasty specimens or normal breast tissues samples (5 cms away from the tumor) were positive, hNIS was also intensely positive in 9 out of 10 (90%) infiltrating duct carcinoma tissues and moderately positive in one case. These preliminary results show that hNIS was present in high frequency as demonstrated by immunohistochemistry in fibroadenoma breast.

  16. Mammary radioiodine accumulation due to functional sodium iodide symporter expression in a benign fibroadenoma

    International Nuclear Information System (INIS)

    Berger, F.; Unterholzner, S.; Diebold, J.; Knesewitsch, P.; Hahn, K.; Spitzweg, C.

    2006-01-01

    The sodium iodide symporter (NIS) has been characterized to mediate the active transport of iodide not only in the thyroid gland but also in various non-thyroidal tissues, including lactating mammary gland and the majority of breast cancers, thereby offering the possibility of diagnostic and therapeutic radioiodine application in breast cancer. In this report, we present a 57-year-old patient with multifocal papillary thyroid carcinoma, who showed focal radioiodine accumulation in a lesion in the right breast on a posttherapy 131 I scan following radioiodine therapy. CT and MR-mammography showed a focal solid lesion in the right breast suggestive of a fibroadenoma, which was confirmed by histological examination. Immunostaining of paraffin-embedded tumor tissue sections using a human NIS antibody demonstrated NIS-specific immunoreactivity confined to epithelial cells of mammary ducts. In conclusion, in a thyroid cancer patient we identified a benign fibroadenoma of the breast expressing high levels of functionally active NIS protein as underlying cause of focal mammary radioiodine accumulation on a posttherapy 131 I scan. These data show for the first time that functional NIS expression is not restricted to lactating mammary gland and malignant breast tissue, but can also be detected in benign breast lesions, such as fibroadenomata of the breast

  17. Functional activity of human sodium/iodide symporter in tumor cell lines

    International Nuclear Information System (INIS)

    Petrich, T.; Knapp, W.H.; Poetter, E.

    2003-01-01

    Aim: The sodium/iodide symporter (NIS) actively transports iodide into thyrocytes. Thus, NIS represents a key protein for diagnosis and radioiodine therapy of differentiated thyroid cancer. Additionally, in the future the NIS gene may be used for cancer gene therapy of non-thyroid-derived malignancies. In this study we evaluated the functionality of NIS with respect to iodide uptake in a panel of tumor cell lines and compared this to gene transfer efficiency. Methods: A human NIS-containing expression vector and reporter-gene vectors encoding and beta;-Galactosidase- or EGFP were used for transient transfection of 13 tumor cell lines. Following transfection measurements of NIS-mediated radioiodide uptake using Na 125 I and of transfection efficiency were performed. The latter included β;-Galactosidase activity measurements using a commercial kit and observation by fluorescence microscopy for EGFP expression. Results: In contrast to respective parental cells, most NIS-transfected cell lines displayed high, perchlorate-sensitive radioiodide uptake. Differences in radioiodide uptake between cell lines apparently corresponded to transfection efficiencies, as judged from reporter-gene assays. Conclusion: With respect to iodide uptake we provide evidence that NIS is functional in different cellular context. As iodide uptake capacity appears to be well correlated to gene transfer efficiency, cell type-specific actions on NIS (e. g. post-translational modification such as glycosylation) are not inhibitory to NIS function. Our data support the promising role of NIS in cancer gene therapy strategies. (orig.)

  18. Characterization of a novel sialic acid transporter of the sodium solute symporter (SSS) family and in vivo comparison with known bacterial sialic acid transporters.

    Science.gov (United States)

    Severi, Emmanuele; Hosie, Arthur H F; Hawkhead, Judith A; Thomas, Gavin H

    2010-03-01

    The function of sialic acids in the biology of bacterial pathogens is reflected by the diverse range of solute transporters that can recognize these sugar acids. Here, we use an Escherichia coliDeltananT strain to characterize the function of known and proposed bacterial sialic acid transporters. We discover that the STM1128 gene from Salmonella enterica serovar Typhimurium, which encodes a member of the sodium solute symporter family, is able to restore growth on sialic acid to the DeltananT strain and is able to transport [(14)C]-sialic acid. Using the DeltananT genetic background, we performed a direct in vivo comparison of the transport properties of the STM1128 protein with those of sialic acid transporters of the major facilitator superfamily and tripartite ATP-independent periplasmic families, E. coli NanT and Haemophilus influenzae SiaPQM, respectively. This revealed that both STM1128 and SiaPQM are sodium-dependent and, unlike SiaPQM, both STM1128 and NanT are reversible secondary carriers, demonstrating qualitative functional differences in the properties of sialic acid transporters used by bacteria that colonize humans.

  19. Bicarbonate/chloride antiport in Vero cells: II. Mechanisms for bicarbonate-dependent regulation of intracellular pH

    International Nuclear Information System (INIS)

    Olsnes, S.; Ludt, J.; Tonnessen, T.I.; Sandvig, K.

    1987-01-01

    The rates of bicarbonate-dependent uptake and efflux of 22 Na + in Vero cells were studied and compared with the uptake and efflux of 36 Cl - . Both processes were strongly inhibited by DIDS. Whereas the transport of chloride increased approximately ten-fold when the internal pH was increased over a narrow range around neutrality, the uptake of Na + was much less affected by changes in pH. The bicarbonate-linked uptake of 22 Na + was dependent on internal Cl- but not on internal Na + . At a constant external concentration of HCO 3 -, the amount of 22 Na + associated with the cells increased when the internal concentration of HCO 3 - decreased and vice versa, which is compatible with the possibility that the ion pair NaCO 3 - is the transported species and that the transport is symmetric across the membrane. Bicarbonate inhibited the uptake of 36 Cl - both in the absence and presence of Na + . At alkaline internal pH, HCO 3 - stimulated the efflux of 36 Cl - from preloaded cells, while at acidic internal pH both Na + and HCO 3 - were required to induce 36 Cl - efflux. We propose a model for how bicarbonate-dependent regulation of the internal pH may occur. This model implies the existence of two bicarbonate transport mechanisms that, under physiological conditions, transport OH(-)-equivalents in opposite directions across the plasma membrane

  20. Expression of sodium/iodide symporter transgene in neural stem cells

    International Nuclear Information System (INIS)

    Kim, Yun Hui; Lee, Dong Soo; Kang, Joo Hyun; Lee, Yong Jin; Chung, June Key; Lee, Myung Chul

    2004-01-01

    The ability to noninvasively track the migration of neural progenitor cells would have significant clinical and research implications. We generated stably transfected F3 human neural progenitor cells with human sodium/iodide symporter (hNIS) for noninvasively tracking F3. In this study, the expression patterns of hNIS gene in F3-NIS were examined according to the cultured time and the epigenetic modulation. F3 human neural stem cells had been obtained from Dr. Seung U. Kim (Ajou University, Suwon, Korea). hNIS and hygromycin resistance gene were linked with IRES (internal Ribosome Entry Site) under control of CMV promoter. This construct was transfected to F3 with Liposome. To investigate the restoration of hNIS gene expression in F3-NIS, cells were treated with demethylating agent (5-Azacytidine) and Histone deacetylase inhibitor (Trichostatin A: TSA). The expression of hNIS was measured by I-125 uptake assay and RT-PCR analysis. The iodide uptake of the F3-NIS was higher 12.86 times than F3 cell line. According to the cell passage number, hNIS expression in F3-NIS gradually diminished. After treatment of 5-Azacytidine and TSA with serial doses (up to 20μM, up to 62.5nM, respectively) for 24 hours, I-125 uptake and mRNA of hNIS in F3-NIS were increased. These results suggest that hNIS transfected F3 might undergo a change in its biological characters by cell passage. Therefore, the gene expression of exogenous gene transferred human stem cell might be affected to the epigenetic modulation such as promoter methylation and Histone deacetylation and to the cell culture conditions

  1. Transfer of the sodium/iodide symporter gene into gliomas for radioiodine therapy in vitro

    International Nuclear Information System (INIS)

    Tan Jian; Li Wei; Liu Xiaohua; Xiao Qian; Jia Qiang; Li Ning

    2008-01-01

    Objective: The most frequent brain tumors are the gliomas. Glioblastomas are largely incurable secondary, to their rapid, aggressive and diffusely infiltrative growth pattern and hypervascularity. This study aimed at investigating the possibility of transecting human sodium/iodide symporter (hNIS) gene into human glioma cell lines to facilitate radioactive iodide treatment in vitro. Methods: Transecting hNIS gene into human glioma cell lines U251 was performed by recombinant expression plasmids with lipofectamine 2000-plasmid complexes. The hNIS gene cell lines with stable expression (hNIS-U251) were selected through G418 antibiotic constraint. The hNIS-U251 gene cell lines were then evaluated for their biologic functions, including 125 I uptake assay, 125 I influx-course, 125 I-efflux-course, 131 I inhibitory effect on cellular proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyhe-trazolium bromide (MTT) assay and flow cytometer. Results: We were successful in transecting hNIS gene into human glioma cell lines by recombinant expression plasmids, and were able to obtain hNIS gene cell lines (hNIS-U251) with stable expression. The hNIS-U251 cell lines could intake and bind radioactive iodide by hNIS gene. The uptakes of 125 I were 117 fold higher in hNIS-U251 cell lines than U251 cell lines [(50 469.88 ± 997.29), (432.92 ± 89.28) counts·min -1 , respectively]. And the proliferation index of hNIS-U251 cell lines was lower than U251 cell lines after incubating with 131 I. Conclusion: The hNIS gene with stable gene expression (hNIS- U251) cell lines could be labeled by 131 I with a high efficiency, thereby may function effectively in the treatment of glioma-related brain tumors. (authors)

  2. Radioiodine uptake of undifferentiated thyroid cancer cells by adenovirus-mediated Na+/ I- symporter gene transfer

    Energy Technology Data Exchange (ETDEWEB)

    So, Y.; Lee, Y. J.; Shin, J. H.; Oh, H. J.; Chung, J. K.; Lee, M. C.; Cho, B. Y. [College of Medicine, Univ. of Seoul National, Seoul (Korea, Republic of); Lee, K. H. [Samsung Medical Center, Seoul (Korea, Republic of)

    2003-07-01

    To increase radioiodine uptake on undifferentiated thyroid cancer cell (ARO cells) by adenovirus-mediated human Na+/I- symporter (hNIS) gene transfer. Recombinant adenovirus Ad-hNIS was manufactured successfully. After transfecting Ad-hNIS on ARO cells, in vitro I-125 uptake and efflux studies were performed. For in vivo studies, 1.510'8 p.f.u. (50 1) of Ad-hNIS was injected into xenograft ARO tumors on the R thigh of BALB/c nu/nu mice (n=12), and same amount of normal saline was injected into xenograft ARO tumors on the L thigh. Two, 3, 4 and 6 days after intratumoral injection of Ad-hNIS, I-131 images (3 mice per day) were taken and xenograft tumors on both thighs were all excised. Total RNA was extracted from each tumor tissue and RT-PCR was performed to confirm the hNIS expression of Ad-hNIS injected xenograft ARO tumors. I-125 uptake of Ad-hNIS transfected ARO cells was increased up to 233 folds at 120 minutes in vitro. I-125 efflux study revealed rapid washout of I-125 from Ad-hNIS transfected ARO cells. On dynamic image, I-131 uptake of Ad-hNIS injected ARO tumor was continuously increased until 60 minutes. Mean count ratios of xenograft ARO tumors (R/L) of 60 minutes I-131 images at 2, 3, 4 and 6 days after Ad-hNIS injection were 2.85, 2.54, 2.31, and 2.18, each. On RT-PCR, hNIS expression of Ad-hNIS transfected ARO xenograft tumors was confirmed. Radioiodine uptake was successfully increased in ARO cells by adenovirus-mediated hNIs gene transfer both in vitro and in vivo.

  3. Comparison of Na+/I- symporter expression rate in malignant and benign thyroid diseases: immunohistochemical study

    International Nuclear Information System (INIS)

    Kang, Do Young; Jeong, Young Jin; Lee, Kyung Eun; Park, Heon Soo; Yoo, Young Hyun; Roh, Mee Sook

    2006-01-01

    Previous studies have not showed consistent results for the level of expression of sodium/iodide symporter (NIS) in thyroid diseases, especially malignant tumor. We undertook this study to evaluate the distribution of NIS expression in malignant thyroid diseases and compare with that in benign thyoid disease. Total patients were 119 cases (Men 15, 48±13 yrs). Total number of samples were 205 pieces. In malignant thyroid disease, there were 153 samples: 90 in papillary carcinoma, 4 in follicular carcinoma, 2 in medullary carcinoma and 57 in metastatic lymph node. In benign thyroid disease, there were 52 samples: 36 in goiter/cyst, 11 in thyroiditis and 5 in follicular adenoma. Using immunohistochemical methods, we probed 205 samples with monoclonal anti-NIS Ab. Grading of staining was scored as 0 (negative or absent), 1 (weakly positive), 2 (moderately positive) or 3 (strongly positive). Expression rate (ER) of NIS positivity in individual disease entity was expressed as percentage of total number divided by number in 2 plus 3 grade. ERs of malignant thyroid diseases were 63% in papillary carcinoma, 81% in metastatic lymph node, 71% in follicular carcinoma and 100% in medullary carcinoma. ERs of benign thyroid disease were 53% in goiter/cyst, 64% in thyroiditis and 40% in follicular adenoma. ER of benign thyroid deceases was higher than benign thyroid diseases (71% vs 54%). Grading of NIS expression in papillary carcinoma or goiter/cyst was heterogeneously distributed in considerable cases. Normal tissue also showed heterogeneous distribution or NIS expression, which was not correlated with that of primary lesion. In papillary thyroid carcinoma, distribution of NIS expression was heterogeneous and increased, and not different compared with that of benign thyroid disease

  4. 1,25-(OH)2-vitamin D3 enhances the cytotoxic effect of radioiodine therapy in prostate cancer cells expressing the sodium iodide symporter

    International Nuclear Information System (INIS)

    Spitzweg, Christine; Hirschmann, Martin; Unterholzner, Stefanie; Cengic, Neziha; Eckel, Petra; Sharif-Samani, Bibi-Rana; Willhauck, Michael J.; Goeke, Burkhard; Morris, John C.

    2005-01-01

    Full text: We reported recently the induction of androgen-dependent iodide uptake activity in human prostate cancer cells (LNCaP) utilizing a prostate-specific antigen (PSA)-promoter directed expression of the sodium iodide symporter (NIS) gene. This offers the potential to treat prostate cancer with radioiodine. In the current study we examined the regulation of PSA-promoter directed NIS expression and therapeutic effectiveness of 131 I in LNCaP cells by 1,25-(OH)2-Vitamin D3 (Vit D3). For this purpose, NIS mRNA and protein expression levels in the NIS-transfected LNCaP cell line NP-1 were examined by Northern and Western blot analysis following incubation with Vit D3 (10 -9 M - 10 -5 M) in the presence of mibolerone (10 -9 M). In addition, NIS functional activity was measured by iodide uptake assay, and in vitro cytotoxicity of 131 I was examined by in vitro clonogenic assay. Following incubation with Vit D3, NIS mRNA levels in NP-1 cells were stimulated 1.2-fold, whereas NIS protein levels increased 1.65-fold and iodide accumulation was stimulated 1.4-fold in a concentration-dependent manner. Further, the selective killing effect of 131 I in NP-1 cells was significantly increased from 55% in NP-1 cells incubated with mibolerone alone to 86 % in NP-1 cells treated with Vit D3 (10 -5 M) in the presence of mibolerone. In the absence of androgen, with or without Vit D3 no functional NIS expression was detected. Conclusion: Treatment with Vit D3 increases androgen-induced NIS expression levels and selective killing effect of 131 I in prostate cancer cells stably expressing NIS under the control of the PSA promoter. Vit D3 may therefore be used to enhance the therapeutic response to radioiodine in prostate cancer cells following PSA-promoter directed NIS gene delivery. (author)

  5. Sodium Solute Symporter and Cadherin Proteins Act as Bacillus thuringiensis Cry3Ba Toxin Functional Receptors in Tribolium castaneum*

    Science.gov (United States)

    Contreras, Estefanía; Schoppmeier, Michael; Real, M. Dolores; Rausell, Carolina

    2013-01-01

    Understanding how Bacillus thuringiensis (Bt) toxins interact with proteins in the midgut of susceptible coleopteran insects is crucial to fully explain the molecular bases of Bt specificity and insecticidal action. In this work, aminopeptidase N (TcAPN-I), E-cadherin (TcCad1), and sodium solute symporter (TcSSS) have been identified by ligand blot as putative Cry3Ba toxin-binding proteins in Tribolium castaneum (Tc) larvae. RNA interference knockdown of TcCad1 or TcSSS proteins resulted in decreased susceptibility to Cry3Ba toxin, demonstrating the Cry toxin receptor functionality for these proteins. In contrast, TcAPN-I silencing had no effect on Cry3Ba larval toxicity, suggesting that this protein is not relevant in the Cry3Ba toxin mode of action in Tc. Remarkable features of TcSSS protein were the presence of cadherin repeats in its amino acid sequence and that a TcSSS peptide fragment containing a sequence homologous to a binding epitope found in Manduca sexta and Tenebrio molitor Bt cadherin functional receptors enhanced Cry3Ba toxicity. This is the first time that the involvement of a sodium solute symporter protein as a Bt functional receptor has been demonstrated. The role of this novel receptor in Bt toxicity against coleopteran insects together with the lack of receptor functionality of aminopeptidase N proteins might account for some of the differences in toxin specificity between Lepidoptera and Coleoptera insect orders. PMID:23645668

  6. Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus

    Directory of Open Access Journals (Sweden)

    Mittra Arjun

    2011-03-01

    Full Text Available Abstract Introduction Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide symporter (hNIS cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153. Methods GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry hNIS via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of hNIS in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenografts was assessed via positron emission tomography (PET utilizing carrier-free 124I radiotracer. Results GLV-1h153 infected, replicated within, and killed PANC-1 cells as efficiently as GLV-1h68. GLV-1h153 provided dose-dependent levels of hNIS expression in infected cells. Immunofluorescence detected transport of the protein to the cell membrane prior to cell lysis, enhancing hNIS-specific radiouptake (P In vivo, GLV-1h153 was as safe and effective as GLV-1h68 in regressing pancreatic cancer xenografts (P 124I-PET. Conclusion Insertion of the hNIS gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy.

  7. Radiochemotherapy of hepatocarcinoma via lentivirus-mediated transfer of human sodium iodide symporter gene and herpes simplex virus thymidine kinase gene

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    Chen Libo, E-mail: libochen888@hotmail.com [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China); Guo Guoying [Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018 (China); Liu Tianjing; Guo Lihe [Division of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Zhu Ruisen [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China)

    2011-07-15

    Herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system has been widely used as a traditional gene therapy modality, and the sodium/iodide symporter gene (NIS) has been found to be a novel therapeutic gene. Since the therapeutic effects of radioiodine therapy or prodrug chemotherapy on cancers following NIS or HSV-TK gene transfer need to be enhanced, this study was designed to investigate the feasibility of radiochemotherapy for hepatocarcinoma via coexpression of NIS gene and HSV-TK gene. Methods: HepG2 cells were stably transfected with NIS, TK and GFP gene via recombinant lentiviral vector and named HepG2/NTG. Gene expression was examined by reverse transcriptase polymerase chain reaction, fluorescence imaging and iodide uptake. The therapeutic effects were assessed by MTT assay and clonogenic assay. Results: HepG2/NTG cells concentrated {sup 125}I{sup -} up to 76-fold higher than the wild-type cells within 20 min, and the efflux happened with a T{sub 1/2eff} of less than 10 min. The iodide uptake in HepG2/NTG cells was specifically inhibited by sodium perchlorate. Dose-dependent toxicity to HepG2/NTG cells by either GCV or {sup 131}I was revealed by clonogenic assay and MTT assay, respectively. The survival rate of HepG2/NTG cells decreased to 49.7%{+-}2.5%, 43.4%{+-}2.8% and 8.6%{+-}1.2% after exposure to {sup 131}I, GCV and combined therapy, respectively. Conclusion: We demonstrate that radiochemotherapy of hepatocarcinoma via lentiviral-mediated coexpression of NIS gene and HSV-TK gene leads to stronger killing effect than single treatment, and in vivo studies are needed to verify these findings.

  8. Radiochemotherapy of hepatocarcinoma via lentivirus-mediated transfer of human sodium iodide symporter gene and herpes simplex virus thymidine kinase gene

    International Nuclear Information System (INIS)

    Chen Libo; Guo Guoying; Liu Tianjing; Guo Lihe; Zhu Ruisen

    2011-01-01

    Herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system has been widely used as a traditional gene therapy modality, and the sodium/iodide symporter gene (NIS) has been found to be a novel therapeutic gene. Since the therapeutic effects of radioiodine therapy or prodrug chemotherapy on cancers following NIS or HSV-TK gene transfer need to be enhanced, this study was designed to investigate the feasibility of radiochemotherapy for hepatocarcinoma via coexpression of NIS gene and HSV-TK gene. Methods: HepG2 cells were stably transfected with NIS, TK and GFP gene via recombinant lentiviral vector and named HepG2/NTG. Gene expression was examined by reverse transcriptase polymerase chain reaction, fluorescence imaging and iodide uptake. The therapeutic effects were assessed by MTT assay and clonogenic assay. Results: HepG2/NTG cells concentrated 125 I - up to 76-fold higher than the wild-type cells within 20 min, and the efflux happened with a T 1/2eff of less than 10 min. The iodide uptake in HepG2/NTG cells was specifically inhibited by sodium perchlorate. Dose-dependent toxicity to HepG2/NTG cells by either GCV or 131 I was revealed by clonogenic assay and MTT assay, respectively. The survival rate of HepG2/NTG cells decreased to 49.7%±2.5%, 43.4%±2.8% and 8.6%±1.2% after exposure to 131 I, GCV and combined therapy, respectively. Conclusion: We demonstrate that radiochemotherapy of hepatocarcinoma via lentiviral-mediated coexpression of NIS gene and HSV-TK gene leads to stronger killing effect than single treatment, and in vivo studies are needed to verify these findings.

  9. Towards a biochemical and structural characterisation of the sodium-iodide sym-porter (Nis)

    International Nuclear Information System (INIS)

    Darrouzet, E.; Marcellin, D.; Huc, S.; Quemeneur, E.; Pourcher, T.

    2006-01-01

    Iodide is essential for thyroid hormone biosynthesis in mammals, and therefore for the control of cell metabolism and the development of the central nervous system in the foetus and newborns, but is relatively scarce element in the environment. To ensure its accumulation, the thyroid gland has evolved a remarkably efficient system, the sodium-iodide sym-porter (NIS), that was first characterized at the molecular level 10 years ago (1). NIS is an intrinsic protein mainly located in the basolateral membrane of thyroid follicular cells where it actively transports iodide ions using the sodium gradient as a driving force (2,3). In addition, this transporter has been found in lactating mammary gland, stomach, and salivary glands, and its mRNA was detected in brain, ovaries, testis. To date, the physiological role of NIS in these organs is not yet identified (3,4).The capacity of NIS to mediate the accumulation of radioactive iodide has been exploited for many years in the diagnosis of thyroid cancer as well as for the detection and radiotherapy of derived metastases. Moreover, the presence of NIS in some breast tumours and the possibility to express it by targeted gene therapy in tumour cells where it is not naturally present could also widen its medical application (4-7). In case of accidental contamination, NIS would also be responsible for accumulation of radioisotopes in the thyroid and for their transfer to the milk and the newborn, eventually causing thyroid cancers. This has motivated our research program in the perspective of designing novel specific therapeutics. During the last decade, the gene encoding the thyroid NIS has been identified and sequenced in various species including rat, mouse and human (1, 8). It was also demonstrated that the protein expression and activity are highly regulated both at the transcriptional and post-translational levels (3). A preliminary topological mode could be drawn from the protein sequence. It proposes a general

  10. Purification and characterization of the reconstitutively active P/sub i//H/sup +/ symporter from rat liver mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, R.S.; Pratt, R.D.; Pedersen, P.L.

    1986-05-01

    A highly purified preparation of reconstitutively active P/sub i//H/sup +/ symporter has been obtained from rat liver mitochondria. The carrier is isolated by extraction of hypotonically shocked mitoplasts with Triton X-114 in the presence of cardiolipin followed by sequential chromatography on hydroxylapatite, DEAE-Sepharose CL-6B, and Affi-Gel 501. Upon incorporation of the final Affi-Gel eluate into phospholipid vesicles, an N-ethylmaleimide (NEM)-sensitive P/sub i//P/sub i/ exchange of greater than 15 ..mu..mol/min/mg protein has been measured. This exchange is characterized by a first order rate constant of 0.85 min/sup -1/ and a t/sub 1/2/ of 49 sec. Furthermore, /sup 32/P/sub i/ uptake into vesicles can be inhibited by SH reagents and by the lysine reactive reagent dansyl chloride. Coomassie-stained SDS polyacrylamide gradient gels verify the high purity of this fraction and indicate the presence of two bands, of nearly equivalent staining intensity, at 33 kDa and 35 kDa. A small amount of higher molecular weight material also appears at approx. 61 kDa. Alkylation of the purified fraction with NEM causes the two lower molecular weight protein bands to migrate as a single species at 35 kDa which binds (/sup 3/H)NEM. It is concluded that the purifed protein represents a nearly homogeneous form of the NEM-sensitive P/sub i//H/sup +/ symporter of rat liver mitochondria. Additionally, the purified carrier appears to contain cysteine and lysine residues that are essential for activity.

  11. Microtubule-dependent relocation of branchial V-H+-ATPase to the basolateral membrane in the Pacific spiny dogfish (Squalus acanthias): a role in base secretion.

    Science.gov (United States)

    Tresguerres, Martin; Parks, Scott K; Katoh, Fumi; Goss, Greg G

    2006-02-01

    We have previously shown that continuous intravenous infusion of NaHCO3 for 24 h ( approximately 1000 micromol kg(-1) h(-1)) results in the relocation of V-H+-ATPase from the cytoplasm to the basolateral membrane in the gills of the Pacific dogfish. To further investigate this putative base-secretive process we performed similar experiments with the addition of colchicine, an inhibitor of cytoskeleton-dependent cellular trafficking processes. Blood pH and plasma total CO2 were significantly higher in the colchicines-treated, HCO3- -infused fish compared with fish infused with HCO3- alone. The effect of colchicine was highest after 24 h of infusion (8.33+/-0.06 vs 8.02+/-0.03 pH units, 15.72+/-3.29 vs 6.74+/-1.34 mmol CO2 l(-1), N=5). Immunohistochemistry and western blotting confirmed that colchicine blocked the transit of V-H+-ATPase to the basolateral membrane. Furthermore, western blotting analyses from whole gill and cell membrane samples suggest that the short-term (6 h) response to alkaline stress consists of relocation of V-H+-ATPases already present in the cell to the basolateral membrane, while in the longer term (24 h) there is both relocation of preexistent enzyme and upregulation in the synthesis of new units. Our results strongly suggest that cellular relocation of V-H+-ATPase is necessary for enhanced HCO3- secretion across the gills of the Pacific dogfish.

  12. Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid secretion in airway epithelia

    Science.gov (United States)

    Turner, Mark J.; Saint‐Criq, Vinciane; Patel, Waseema; Ibrahim, Salam H.; Verdon, Bernard; Ward, Christopher; Garnett, James P.; Tarran, Robert; Cann, Martin J.

    2015-01-01

    Key points Raised arterial blood CO2 (hypercapnia) is a feature of many lung diseases.CO2 has been shown to act as a cell signalling molecule in human cells, notably by influencing the levels of cell signalling second messengers: cAMP and Ca2+.Hypercapnia reduced cAMP‐stimulated cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid transport in Calu‐3 cells and primary human airway epithelia but did not affect cAMP‐regulated HCO3 − transport via pendrin or Na+/HCO3 − cotransporters.These results further support the role of CO2 as a cell signalling molecule and suggests CO2‐induced reductions in airway anion and fluid transport may impair innate defence mechanisms of the lungs. Abstract Hypercapnia is clinically defined as an arterial blood partial pressure of CO2 of above 40 mmHg and is a feature of chronic lung disease. In previous studies we have demonstrated that hypercapnia modulates agonist‐stimulated cAMP levels through effects on transmembrane adenylyl cyclase activity. In the airways, cAMP is known to regulate cystic fibrosis transmembrane conductance regulator (CFTR)‐mediated anion and fluid secretion, which contributes to airway surface liquid homeostasis. The aim of the current work was to investigate if hypercapnia could modulate cAMP‐regulated ion and fluid transport in human airway epithelial cells. We found that acute exposure to hypercapnia significantly reduced forskolin‐stimulated elevations in intracellular cAMP as well as both adenosine‐ and forskolin‐stimulated increases in CFTR‐dependent transepithelial short‐circuit current, in polarised cultures of Calu‐3 human airway cells. This CO2‐induced reduction in anion secretion was not due to a decrease in HCO3 − transport given that neither a change in CFTR‐dependent HCO3 − efflux nor Na+/HCO3 − cotransporter‐dependent HCO3 − influx were CO2‐sensitive. Hypercapnia also reduced the volume of forskolin‐stimulated fluid

  13. Experimental study of the function of the sodium/iodide symporter (nis) in the nude mice bearing breast cancer

    International Nuclear Information System (INIS)

    Fan Wei; Wang Guohui; Zhang Weiguang; Dai Junjin; Yang Xiaochun

    2004-01-01

    Objective: To investigate the function of the sodium / iodide symporter (NIS) and the feasibility of treating breast cancer by studying the distribution and imaging of the nude mice bearing breast cancer. Methods: The animal model of MCF-7/ER(+)-bearing and MCF-7/ER(-)-bearing human breast cancer nude mice were prepared before experiments. The mice were intraperitoneally injected with 131I when tumor grown to 0.8-1 cm . The distribution of 131I in different tissues was detected at different time ( 6, 12, and 24h ). The percentage of the injected dose per gram of tissue (%D/g) and the ratio of Tumor/Non-tumor were calculated. Meanwhile, the nude mice were imaged at different time. Results: The 131I in tumor tissue in the MCF-7/ER(+)group was higher than that of MCF- 7/ER(-) group at 6h after injection, and the %ID/g were 6.13% and 2.37% respectively. The %lD/g at 12 h of two groups were 9.31 and 3.12, and were 11.21 and 3.47 at 24 h. There was a distinguish difference between them (p<0.05). At 12 h, the values of T/NT of blood, heart, lung, intestine and muscle were 2.39,3.06,3.94, 7.69 and 7.60 and were 5.15, 5.47, 5.29, 11.44 and 10.99 at 24 h. The values of T/NT of MCF-7/ER(-) group were much lower than those of MCF-7/ER(+) group. The imaging results showed that there was much radioactivity in tumor tissue in the MCF-7/ER(+) group at 12 h . The control groups has no obvious radioactivity in the tumor tissue all the time. Conclusion: Sodium/iodide symporter expressed in the estrogen-receptor-positive breast cancer tissue could transformed actively 131I into tumor tissue, which suggests 1311 therapy might become a promising way to treat breast cancer. (authors)

  14. Effects of trichostatin a on the expression of sodium/iodide symporter mRNA and the uptake of iodide in human thyroid cancer cell lines

    International Nuclear Information System (INIS)

    Bao Jiandong; Lin Xiufeng; Yu Huixin; Tan Cheng; Zhang Li

    2010-01-01

    Objective: To investigate the sodium/iodide symporter (NIS) expression and iodide uptake in thyroid cancer cells induced by the histone deacetyltransferase inhibitors (HDACi), Trichostatin A (TSA). Methods: Both the thyroid cancer cell lines, follicular thyroid carcinoma cell line FTC-133 and papillary thyroid carcinoma cell line K1, were firstly induced with TSA for 48 h. Then, the expression of NIS mRNA was analysed with reverse transcription-polymerase chain reaction (RT-PCR), the densitometric ratio of NIS/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was calculated, and the iodide uptake in the thyroid cancer cells was also measured. Independent-sample t-test and one-way analysis of variance (ANOVA) were used to analyze the data. Results: For FTC-133 cells, increased NIS mRNA expression was detected after 48 h of TSA treatment, and the changes were dose-dependent (F=32.56, P 0.05). Furthermore, FTC-133 cells showed the ability of accumulating radioiodide with 50 and 75 nmol/L TSA induction for 48 h: (15.42 ± 0.42) x 10 3 counts · min -1 · 10 -5 cells vs (8.46 ± 0.84) x 10 3 counts · min -1 · 10 -5 cells, t=3.018, P 3 counts · min -1 · 10 -5 cells vs (8.46 ± 0.84) x 10 3 counts · min -1 · 10 -5 cells, t=3.557, P 3 counts · min -1 · 10 -5 cells, (6.97 ± 0.65) x 10 3 counts · min -1 · 10 -5 cells vs (5.37 ± 0.88) x 10 3 counts · min -1 · 10 -5 cells, t=0.185, P> 0.05 and t = 0.332, P > 0.05, respectively. Conclusion: TSA induced upregulated NIS mRNA expression in follicular thyroid cancer cells and augmented radioiodide uptake in thyroid cancer cells, while TSA had no remarkable effect on papillary thyroid carcinoma cell. (authors)

  15. The solute specificity profiles of nucleobase cation symporter 1 (NCS1) from Zea mays and Setaria viridis illustrate functional flexibility.

    Science.gov (United States)

    Rapp, Micah; Schein, Jessica; Hunt, Kevin A; Nalam, Vamsi; Mourad, George S; Schultes, Neil P

    2016-03-01

    The solute specificity profiles (transport and binding) for the nucleobase cation symporter 1 (NCS1) proteins, from the closely related C4 grasses Zea mays and Setaria viridis, differ from that of Arabidopsis thaliana and Chlamydomonas reinhardtii NCS1. Solute specificity profiles for NCS1 from Z. mays (ZmNCS1) and S. viridis (SvNCS1) were determined through heterologous complementation studies in NCS1-deficient Saccharomyces cerevisiae strains. The four Viridiplantae NCS1 proteins transport the purines adenine and guanine, but unlike the dicot and algal NCS1, grass NCS1 proteins fail to transport the pyrimidine uracil. Despite the high level of amino acid sequence similarity, ZmNCS1 and SvNCS1 display distinct solute transport and recognition profiles. SvNCS1 transports adenine, guanine, hypoxanthine, cytosine, and allantoin and competitively binds xanthine and uric acid. ZmNCS1 transports adenine, guanine, and cytosine and competitively binds, 5-fluorocytosine, hypoxanthine, xanthine, and uric acid. The differences in grass NCS1 profiles are due to a limited number of amino acid alterations. These amino acid residues do not correspond to amino acids essential for overall solute and cation binding or solute transport, as previously identified in bacterial and fungal NCS1, but rather may represent residues involved in subtle solute discrimination. The data presented here reveal that within Viridiplantae, NCS1 proteins transport a broad range of nucleobase compounds and that the solute specificity profile varies with species.

  16. An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I- symporter (NIS) knockout mice.

    Science.gov (United States)

    Ferrandino, Giuseppe; Kaspari, Rachel R; Reyna-Neyra, Andrea; Boutagy, Nabil E; Sinusas, Albert J; Carrasco, Nancy

    2017-07-13

    The sodium/iodide symporter (NIS) mediates active iodide (I - ) accumulation in the thyroid, the first step in thyroid hormone (TH) biosynthesis. Mutations in the SLC5A5 gene encoding NIS that result in a non-functional protein lead to congenital hypothyroidism due to I - transport defect (ITD). ITD is a rare autosomal disorder that, if not treated promptly in infancy, can cause mental retardation, as the TH decrease results in improper development of the nervous system. However, in some patients, hypothyroidism has been ameliorated by unusually large amounts of dietary I - . Here we report the first NIS knockout (KO) mouse model, obtained by targeting exons 6 and 7 of the Slc5a5 gene. In NIS KO mice, in the thyroid, stomach, and salivary gland, NIS is absent, and hence there is no active accumulation of the NIS substrate pertechnetate ( 99m TcO 4 - ). NIS KO mice showed undetectable serum T 4 and very low serum T 3 levels when fed a diet supplying the minimum I - requirement for rodents. These hypothyroid mice displayed oxidative stress in the thyroid, but not in the brown adipose tissue or liver. Feeding the mice a high-I - diet partially rescued TH biosynthesis, demonstrating that, at high I - concentrations, I - enters the thyroid through routes other than NIS.

  17. Congenital Hypothyroidism Caused by a PAX8 Gene Mutation Manifested as Sodium/Iodide Symporter Gene Defect

    Directory of Open Access Journals (Sweden)

    Wakako Jo

    2010-01-01

    Full Text Available Loss-of-function mutations of the PAX8 gene are considered to mainly cause congenital hypothyroidism (CH due to thyroid hypoplasia. However, some patients with PAX8 mutation have demonstrated a normal-sized thyroid gland. Here we report a CH patient caused by a PAX8 mutation, which manifested as iodide transport defect (ITD. Hypothyroidism was detected by neonatal screening and L-thyroxine replacement was started immediately. Although 123I scintigraphy at 5 years of age showed that the thyroid gland was in the normal position and of small size, his iodide trapping was low. The ratio of the saliva/plasma radioactive iodide was low. He did not have goiter; however laboratory findings suggested that he had partial ITD. Gene analyses showed that the sodium/iodide symporter (NIS gene was normal; instead, a mutation in the PAX8 gene causing R31H substitution was identified. The present report demonstrates that individuals with defective PAX8 can have partial ITD, and thus genetic analysis is useful for differential diagnosis.

  18. Low Iodine in the Follicular Lumen Caused by Cytoplasm Mis-localization of Sodium Iodide Symporter may Induce Nodular Goiter.

    Science.gov (United States)

    Huang, Huibin; Shi, Yaxiong; Liang, Bo; Cai, Huiyao; Cai, Qingyan

    2017-10-01

    Iodine is a key ingredient in the synthesis of thyroid hormones and also a major factor in the regulation of thyroid function. A local reduction of iodine content in follicular lumen leads to overexpression of local thyroid-stimulating hormone receptor (TSHr), which in turn excessively stimulates the regional thyroid tissue, and result in the formation of nodular goiter. In this study, we investigated the relationship between iodine content and sodium iodide symporter (NIS) expression by using the clinical specimens from patients with nodular goiter and explored the pathogenesis triggered by iodine deficiency in nodular goiter. In total, 28 patients were clinically histopathologically confirmed to have nodular goiter and the corresponding adjacent normal thyroid specimens were harvested simultaneously. Western blot and immunohistochemistry were performed to assay NIS expression and localization in thyrocytes of both nodular goiter and adjacent normal thyroid tissues. NIS expression mediated by iodine in follicular lumen was confirmed by follicular model in vitro. Meanwhile, radioscan with iodine-131were conducted on both nodular goiter and adjacent normal thyroid. Our data showed that NIS expression in nodular goiter was significantly higher than that in adjacent normal tissues, which was associated with low iodine in the follicular lumen. Abnormal localization of NIS and lower amount of radioactive iodine-131 were also found in nodular goiter. Our data implied that low iodine in the follicular lumen caused by cytoplasm mis-localization of NIS may induce nodular goiter.

  19. Abnormal radioiodine uptake on post-therapy whole body scan and sodium/iodine symporter expression in a dermoid cyst of the ovary: report of a case and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Campenni, Alfredo; Baldari, Sergio, E-mail: acampenni@unime.ittalia [Dipartimento di Scienze Biomediche e delle Immagini Morfologiche e Funzionali, Unità di Medicina Nucleare, Università degli Studi di Messina, Messina (Italy); Giovinazzo, Salvatore; Ruggeri, Rosaria M. [Dipartimento di Medicina Clinica e Sperimentale, Unità di Endocrinologia, Università degli Studi di Messina (Italy); Tuccari, Giovanni [Dipartimento di Patologia Umana, Università degli Studi di Messina (Italy); Fogliani, Simone [Unità di Scienze Radiologiche, Ospedale di Milazzo, Messina (Italy)

    2015-08-15

    In patients affected by differentiated thyroid cancer, the whole-body scan (WBS) with 131-radioiodine, especially when performed after a therapeutic activity of {sup 131}I, represents a sensitive procedure for detecting thyroid remnant and/or metastatic disease. Nevertheless, a wide spectrum of potentially pitfalls has been reported. Herein we describe a 63-year-old woman affected by follicular thyroid cancer, who was accidentally found to have an abdominal mass at post-dose WBS (pWBS). pWBS showed abnormal radioiodine uptake in the upper mediastinum, consistent with lymph-node metastases, and a slight radioiodine uptake in an abdominal focal area. Computed tomography revealed an inhomogeneous mass in the pelvis, previously unrecognized. The lesion, surgically removed, was found to be a typical dermoid cyst of the ovary, without any evidence of thyroid tissue. By immunohistochemistry, a moderate expression of the sodium-iodine symporter (NIS) was demonstrated in the epithelial cells, suggesting a NIS-dependent uptake of radioiodine by the cyst. (author)

  20. Chloroquine uptake, altered partitioning and the basis of drug resistance: evidence for chloride-dependent ionic regulation.

    Science.gov (United States)

    Martiney, J A; Ferrer, A S; Cerami, A; Dzekunov, S; Roepe, P

    1999-01-01

    The biochemical mechanism of chloroquine resistance in Plasmodium falciparum remains unknown. We postulated that chloroquine-resistant strains could alter ion fluxes that then indirectly control drug accumulation within the parasite by affecting pH and/or membrane potential ('altered partitioning mechanism'). Two principal intracellular pH-regulating systems in many cell types are the amiloride-sensitive Na+/H+ exchanger (NHE), and the sodium-independent, stilbene-sensitive Cl-/HCO3- antiporter (AE). We report that under physiological conditions (balanced CO2 and HCO3-) chloroquine uptake and susceptibility are not altered by amiloride analogues. We also do not detect a significant difference in NHE activity between chloroquine-sensitive and chloroquine-resistant strains via single cell photometry methods. AE activity is dependent on the intracellular and extracellular concentrations of Cl- and HCO3- ions. Chloroquine-resistant strains differentially respond to experimental modifications in chloride-dependent homeostasis, including growth, cytoplasmic pH and pH regulation. Chloroquine susceptibility is altered by stilbene DIDS only on chloroquine-resistant strains. Our results suggest that a Cl(-)-dependent system (perhaps AE) has a significant effect on the uptake of chloroquine by the infected erythrocyte, and that alterations of this biophysical parameter may be part of the mechanism of chloroquine resistance in P. falciparum.

  1. The Leucine transporter from Aquifex aeolicus as a model for the Neurotransmitter Sodium Symporters – insights into function and ligand binding

    DEFF Research Database (Denmark)

    Kantcheva, Adriana Krassimirova

    In her PhD studies, Adriana K. Kantcheva looked into the structural perspective of a bacterial transporter – the leucine transporter from Aquifex aeolicus (LeuT) – which is a homologue to neurotransmitter sodium symporters (NSS) found in humans, such as the serotonin transporter. Two crystal...... structures of LeuT elucidated new insights regarding ion and substrate binding to this transporter. Studying members of the NSS family is important as these proteins are found in the central nervous system of humans at the synaptic cleft and are implicated in serious conditions such as Parkinson’s disease...

  2. Comparison of expressed human and mouse sodium/iodide sym-porters reveals differences in transport properties and subcellular localization

    Energy Technology Data Exchange (ETDEWEB)

    Dayem, M.; Basquin, C.; Navarro, V.; Carrier, P.; Marsault, R.; Lindenthal, S.; Pourcher, T. [Univ Nice Sophia Antipolis, Sch Med, CEA, DSV, iBEB, SBTN, TIRO, F-06107 Nice (France); Chang, P. [CNRS, UPMC Biol Dev, UMR 7009, F-06230 Villefranche Sur Mer (France); Huc, S.; Darrouzet, E. [CEA Valrho, DSV, iBEB, SBTN, F-30207 Bagnols Sur Ceze (France)

    2008-07-01

    The active transport of iodide from the blood stream into thyroid follicular cells is mediated by the Na{sup +}/I{sup -} sym-porter (NIS). We studied mouse NIS (mNIS) and found that it catalyzes iodide transport into transfected cells more efficiently than human NIS (hNIS). To further characterize this difference,we compared {sup 125}I, uptake in the transiently transfected human embryonic kidney (HEK) 293 cells. We found that the Vmax for mNIS was four times higher than that for hNIS, and that the iodide transport constant (Km) was 2-5-fold lower for hNIS than mNIS. We also performed immuno-cyto-localization studies and observed that the subcellular distribution of the two ortho-logs differed. While the mouse protein was predominantly found at the plasma membrane, its human ortho-log was intracellular in {approx} 40% of the expressing cells. Using cell surface protein-labeling assays, we found that the plasma membrane localization frequency of the mouse protein was only 2-5-fold higher than that of the human protein, and therefore cannot alone account for,x values. We reasoned that the difference in the obtained Vmax the observed difference could also be caused by a higher turnover number for iodide transport in the mouse protein. We then expressed and analyzed chimeric proteins. The data obtained with these constructs suggest that the iodide recognition site could be located in the region extending from the N-terminus to transmembrane domain 8, and that the region between transmembrane domain 5 and the C-terminus could play a role in the subcellular localization of the protein. (authors)

  3. Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine

    International Nuclear Information System (INIS)

    Hutzen, Brian; Pierson, Christopher R; Russell, Stephen J; Galanis, Evanthia; Raffel, Corey; Studebaker, Adam W

    2012-01-01

    Medulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV) can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus that encodes the human thyroidal sodium iodide symporter (NIS), has the potential to deliver targeted radiotherapy to the tumor site and promote a localized bystander effect above and beyond that achieved by MV alone. We evaluated the efficacy of MV-NIS against medulloblastoma cells in vitro and examined their ability to incorporate radioiodine at various timepoints, finding peak uptake at 48 hours post infection. The effects of MV-NIS were also evaluated in mouse xenograft models of localized and disseminated medulloblastoma. Athymic nude mice were injected with D283med-Luc medulloblastoma cells in the caudate putamen (localized disease) or right lateral ventricle (disseminated disease) and subsequently treated with MV-NIS. Subsets of these mice were given a dose of 131 I at 24, 48 or 72 hours later. MV-NIS treatment, both by itself and in combination with 131 I, elicited tumor stabilization and regression in the treated mice and significantly extended their survival times. Mice given 131 I were found to concentrate radioiodine at the site of their tumor implantations. In addition, mice with localized tumors that were given 131 I either 24 or 48 hours after MV-NIS treatment exhibited a significant survival advantage over mice given MV-NIS alone. These data suggest MV-NIS plus radioiodine may be a potentially useful therapy for the treatment of medulloblastoma

  4. Monitoring of macrophage accumulation in statin-treated atherosclerotic mouse model using sodium iodide symporter imaging system

    International Nuclear Information System (INIS)

    Yoo, Ran Ji; Kim, Min Hwan; Woo, Sang-Keun; Kim, Kwang Il; Lee, Tae Sup; Choi, Yang-Kyu; Kang, Joo Hyun; Lim, Sang Moo; Lee, Yong Jin

    2017-01-01

    Introduction: Macrophages play a key role in atherosclerotic plaque formation in atherosclerosis, but its detailed understanding has poorly investigated until now. Thus, we sought to demonstrate a noninvasive technique for macrophage tracking to atherosclerotic lesions in apolipoprotein E −/− (ApoE −/− ) mice with an imaging system based on sodium iodide symporter (NIS) gene coupled with 99m Tc-single-photon emission computed tomography (SPECT). Methods and results: Macrophage cells (RAW264.7) were stably transduced with retrovirus expressing NIS gene (RAW-NIS). In RAW-NIS cells, uptake of 125 I was higher than the parental cells. [ 18 F]FDG signals in the aorta at 30 weeks on an ApoE −/− mice with high cholesterol diet were higher (1.7 ± 0.12% injected dose (ID)) than those in control group (0.84 ± 0.06% ID). Through 99m Tc-SPECT/computed tomography (CT), in the RAW-NIS cell injected group, the 99m Tc-pertechnetate uptake in aorta was higher than control groups. However, according to atorvastatin treatment, RAW-NIS cell recruitment reduced to the aorta. Area of 99m Tc-pertechnetate uptake was positively correlated with immunostaining results against macrophage antigen (CD68). Cholesterol and low-density lipoprotein levels of atorvastatin-treated group showed lower than those of atorvastatin-untreated group, but did not reach statistical difference. Conclusions: This novel approach to tracking macrophages to atherosclerotic plaques in vivo can be applied for studies of arterosclerotic vascular disease.

  5. PI3K activation is associated with intracellular sodium/iodide symporter protein expression in breast cancer

    International Nuclear Information System (INIS)

    Knostman, Katherine AB; McCubrey, James A; Morrison, Carl D; Zhang, Zhaoxia; Capen, Charles C; Jhiang, Sissy M

    2007-01-01

    The sodium/iodide symporter (NIS) is a membrane glycoprotein mediating active iodide uptake in the thyroid gland and is the molecular basis for radioiodide imaging and therapeutic ablation of thyroid carcinomas. NIS is expressed in the lactating mammary gland and in many human breast tumors, raising interest in similar use for diagnosis and treatment. However, few human breast tumors have clinically evident iodide uptake ability. We previously identified PI3K signaling as important in NIS upregulation in transgenic mouse models of breast cancer, and the PI3K pathway is commonly activated in human breast cancer. NIS expression, subcellular localization, and function were analyzed in MCF-7 human breast cancer cells and MCF-7 cells stably or transiently expressing PI3K p110alpha subunit using Western blot of whole cell lysate, cell surface biotinylation Western blot and immunofluorescence, and radioiodide uptake assay, respectively. NIS localization was determined in a human breast cancer tissue microarray using immunohistochemical staining (IHC) and was correlated with pre-existing pAkt IHC data. Statistical analysis consisted of Student's t-test (in vitro studies) or Fisher's Exact Test (in vivo correlational studies). In this study, we demonstrate that PI3K activation in MCF-7 human mammary carcinoma cells leads to expression of underglycosylated NIS lacking cell surface trafficking necessary for iodide uptake ability. PI3K activation also appears to interfere with cell surface trafficking of exogenous NIS as well as all-trans retinoic acid-induced endogenous NIS. A correlation between NIS expression and upregulation of PI3K signaling was found in a human breast cancer tissue microarray. Thus, the PI3K pathway likely plays a major role in the discordance between NIS expression and iodide uptake in breast cancer patients. Further study is warranted to realize the application of NIS-mediated radioiodide ablation in breast cancer

  6. Assessment of the Na/I symporter as a reporter gene to visualize oncolytic adenovirus propagation in peritoneal tumours

    International Nuclear Information System (INIS)

    Merron, Andrew; McNeish, Iain A.; Baril, Patrick; Tran, Lucile; Vassaux, Georges; Martin-Duque, Pilar; Vieja, Antonio de la; Briat, Arnaud; Harrington, Kevin J.

    2010-01-01

    In vivo imaging of the spread of oncolytic viruses using the Na/I symporter (NIS) has been proposed. Here, we assessed whether the presence of NIS in the viral genome affects the therapeutic efficacy of the oncolytic adenovirus dl922-947 following intraperitoneal administration, in a mouse model of peritoneal ovarian carcinoma. We generated AdAM7, a dl922-947 oncolytic adenovirus encoding the NIS coding sequence. Iodide uptake, NIS expression, infectivity and cell-killing activity of AdAM7, as well as that of relevant controls, were determined in vitro. In vivo, the propagation of this virus in the peritoneal cavity of tumour-bearing mice was determined using SPECT/CT imaging and its therapeutic efficacy was evaluated. In vitro infection of ovarian carcinoma IGROV-1 cells with ADAM7 led to functional expression of NIS. However, the insertion of NIS into the viral genome resulted in a loss of efficacy of the virus in terms of replication and cytotoxicity. In vivo, on SPECT/CT imaging AdAM7 was only detectable in the peritoneal cavity of animals bearing peritoneal ovarian tumours for up to 5 days after intraperitoneal administration. Therapeutic experiments in vivo demonstrated that AdAM7 is as potent as its NIS-negative counterpart. This study demonstrated that despite the detrimental effect observed in vitro, insertion of the reporter gene NIS in an oncolytic adenovirus did not affect its therapeutic efficacy in vivo. We conclude that NIS is a highly relevant reporter gene to monitor the fate of oncolytic adenovectors in live subjects. (orig.)

  7. Assessment of the Na/I symporter as a reporter gene to visualize oncolytic adenovirus propagation in peritoneal tumours

    Energy Technology Data Exchange (ETDEWEB)

    Merron, Andrew; McNeish, Iain A. [Queen Mary' s School of Medicine and Dentistry, Centre for Molecular Oncology, Institute of Cancer, London (United Kingdom); Baril, Patrick; Tran, Lucile; Vassaux, Georges [CHU Hotel Dieu, INSERM, Nantes (France); CHU de Nantes, Institut des Maladies de l' Appareil Digestif, Nantes (France); Martin-Duque, Pilar [Instituto Aragones de Ciencias de la Salud, Zaragoza (Spain); Vieja, Antonio de la [Instituto de Investigaciones Biomedicas, Madrid (Spain); Briat, Arnaud [INSERM U877, Grenoble (France); Harrington, Kevin J. [Chester Beatty Laboratories, Institute of Cancer Research, London (United Kingdom)

    2010-07-15

    In vivo imaging of the spread of oncolytic viruses using the Na/I symporter (NIS) has been proposed. Here, we assessed whether the presence of NIS in the viral genome affects the therapeutic efficacy of the oncolytic adenovirus dl922-947 following intraperitoneal administration, in a mouse model of peritoneal ovarian carcinoma. We generated AdAM7, a dl922-947 oncolytic adenovirus encoding the NIS coding sequence. Iodide uptake, NIS expression, infectivity and cell-killing activity of AdAM7, as well as that of relevant controls, were determined in vitro. In vivo, the propagation of this virus in the peritoneal cavity of tumour-bearing mice was determined using SPECT/CT imaging and its therapeutic efficacy was evaluated. In vitro infection of ovarian carcinoma IGROV-1 cells with ADAM7 led to functional expression of NIS. However, the insertion of NIS into the viral genome resulted in a loss of efficacy of the virus in terms of replication and cytotoxicity. In vivo, on SPECT/CT imaging AdAM7 was only detectable in the peritoneal cavity of animals bearing peritoneal ovarian tumours for up to 5 days after intraperitoneal administration. Therapeutic experiments in vivo demonstrated that AdAM7 is as potent as its NIS-negative counterpart. This study demonstrated that despite the detrimental effect observed in vitro, insertion of the reporter gene NIS in an oncolytic adenovirus did not affect its therapeutic efficacy in vivo. We conclude that NIS is a highly relevant reporter gene to monitor the fate of oncolytic adenovectors in live subjects. (orig.)

  8. Comparison of expressed human and mouse sodium/iodide sym-porters reveals differences in transport properties and subcellular localization

    International Nuclear Information System (INIS)

    Dayem, M.; Basquin, C.; Navarro, V.; Carrier, P.; Marsault, R.; Lindenthal, S.; Pourcher, T.; Chang, P.; Huc, S.; Darrouzet, E.

    2008-01-01

    The active transport of iodide from the blood stream into thyroid follicular cells is mediated by the Na + /I - sym-porter (NIS). We studied mouse NIS (mNIS) and found that it catalyzes iodide transport into transfected cells more efficiently than human NIS (hNIS). To further characterize this difference,we compared 125 I, uptake in the transiently transfected human embryonic kidney (HEK) 293 cells. We found that the Vmax for mNIS was four times higher than that for hNIS, and that the iodide transport constant (Km) was 2-5-fold lower for hNIS than mNIS. We also performed immuno-cyto-localization studies and observed that the subcellular distribution of the two ortho-logs differed. While the mouse protein was predominantly found at the plasma membrane, its human ortho-log was intracellular in ∼ 40% of the expressing cells. Using cell surface protein-labeling assays, we found that the plasma membrane localization frequency of the mouse protein was only 2-5-fold higher than that of the human protein, and therefore cannot alone account for,x values. We reasoned that the difference in the obtained Vmax the observed difference could also be caused by a higher turnover number for iodide transport in the mouse protein. We then expressed and analyzed chimeric proteins. The data obtained with these constructs suggest that the iodide recognition site could be located in the region extending from the N-terminus to transmembrane domain 8, and that the region between transmembrane domain 5 and the C-terminus could play a role in the subcellular localization of the protein. (authors)

  9. Comparison of Na{sup +}/I{sup -} symporter expression rate in malignant and benign thyroid diseases: immunohistochemical study

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Do Young; Jeong, Young Jin; Lee, Kyung Eun; Park, Heon Soo; Yoo, Young Hyun; Roh, Mee Sook [Donga University College of Medicine, Busan (Korea, Republic of)

    2006-02-15

    Previous studies have not showed consistent results for the level of expression of sodium/iodide symporter (NIS) in thyroid diseases, especially malignant tumor. We undertook this study to evaluate the distribution of NIS expression in malignant thyroid diseases and compare with that in benign thyoid disease. Total patients were 119 cases (Men 15, 48{+-}13 yrs). Total number of samples were 205 pieces. In malignant thyroid disease, there were 153 samples: 90 in papillary carcinoma, 4 in follicular carcinoma, 2 in medullary carcinoma and 57 in metastatic lymph node. In benign thyroid disease, there were 52 samples: 36 in goiter/cyst, 11 in thyroiditis and 5 in follicular adenoma. Using immunohistochemical methods, we probed 205 samples with monoclonal anti-NIS Ab. Grading of staining was scored as 0 (negative or absent), 1 (weakly positive), 2 (moderately positive) or 3 (strongly positive). Expression rate (ER) of NIS positivity in individual disease entity was expressed as percentage of total number divided by number in 2 plus 3 grade. ERs of malignant thyroid diseases were 63% in papillary carcinoma, 81% in metastatic lymph node, 71% in follicular carcinoma and 100% in medullary carcinoma. ERs of benign thyroid disease were 53% in goiter/cyst, 64% in thyroiditis and 40% in follicular adenoma. ER of benign thyroid deceases was higher than benign thyroid diseases (71% vs 54%). Grading of NIS expression in papillary carcinoma or goiter/cyst was heterogeneously distributed in considerable cases. Normal tissue also showed heterogeneous distribution or NIS expression, which was not correlated with that of primary lesion. In papillary thyroid carcinoma, distribution of NIS expression was heterogeneous and increased, and not different compared with that of benign thyroid disease.

  10. Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine

    Directory of Open Access Journals (Sweden)

    Hutzen Brian

    2012-11-01

    Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus that encodes the human thyroidal sodium iodide symporter (NIS, has the potential to deliver targeted radiotherapy to the tumor site and promote a localized bystander effect above and beyond that achieved by MV alone. Methods We evaluated the efficacy of MV-NIS against medulloblastoma cells in vitro and examined their ability to incorporate radioiodine at various timepoints, finding peak uptake at 48 hours post infection. The effects of MV-NIS were also evaluated in mouse xenograft models of localized and disseminated medulloblastoma. Athymic nude mice were injected with D283med-Luc medulloblastoma cells in the caudate putamen (localized disease or right lateral ventricle (disseminated disease and subsequently treated with MV-NIS. Subsets of these mice were given a dose of 131I at 24, 48 or 72 hours later. Results MV-NIS treatment, both by itself and in combination with 131I, elicited tumor stabilization and regression in the treated mice and significantly extended their survival times. Mice given 131I were found to concentrate radioiodine at the site of their tumor implantations. In addition, mice with localized tumors that were given 131I either 24 or 48 hours after MV-NIS treatment exhibited a significant survival advantage over mice given MV-NIS alone. Conclusions These data suggest MV-NIS plus radioiodine may be a potentially useful therapy for

  11. Imaging of human sodium-iodide symporter gene expression mediated by recombinant adenovirus in skeletal muscle of living rats

    International Nuclear Information System (INIS)

    Yang, Hyun Suk; Park, Seong-Wook; Lee, Heuiran; Kim, Sung Jin; Lee, Won Woo; Yang, You-Jung; Moon, Dae Hyuk

    2004-01-01

    We evaluated the feasibility of non-invasive imaging of recombinant adenovirus-mediated human sodium-iodide symporter (hNIS) gene expression by 99m TcO 4 - scintigraphy in skeletal muscle of rats. Replication-defective recombinant adenovirus encoding hNIS gene [Rad-CMV-hNIS 5 x 10 7 , 2 x 10 8 or 1 x 10 9 plaque forming units (pfu)] or β-galactosidase gene (Rad-CMV-LacZ 1 x 10 9 pfu) was injected into the right biceps femoris muscle of rats (n=5-6 for each group). Three days after gene transfer, scintigraphy was performed using a gamma camera 30 min after injection of 99m TcO 4 - (1.85 MBq). An additional two rats injected with 1 x 10 9 pfu of Rad-CMV-hNIS underwent 99m TcO 4 - scintigraphy with sodium perchlorate. After the imaging studies, rats were sacrificed for assessment of the biodistribution of 99m TcO 4 - and measurement of hNIS mRNA expression. In all the rats injected with 1 x 10 9 pfu of Rad-CMV-hNIS, hNIS expression was successfully imaged by 99m TcO 4 - scintigraphy, while rats injected with Rad-CMV-LacZ or lower doses of Rad-CMV-hNIS failed to show uptake. The biodistribution studies indicated that a significantly different amount of 99m TcO 4 - was retained in the liver (p 9 pfu of Rad-CMV-hNIS. The muscular hNIS mRNA level quantified by real-time reverse transcription-polymerase chain reaction was significantly higher in rats injected with 1 x 10 9 pfu of Rad-CMV-hNIS (p 9 pfu of Rad-CMV-hNIS were specifically inhibited by sodium perchlorate. This study illustrated that 99m TcO 4 - scintigraphy can monitor Rad-CMV-hNIS-mediated gene expression in skeletal muscle of rats, non-invasively and quantitatively. (orig.)

  12. Feasibility of sodium/iodide symporter gene as a new imaging reporter gene: comparison with HSV1-tk

    International Nuclear Information System (INIS)

    Shin, Jae Hoon; Chung, June-Key; Lee, Yong Jin; Kim, Kwang Il; Kang, Joo Hyun; Jeong, Jae Min; Lee, Dong Soo; Kim, Chul Woo; Lee, Myung Chul

    2004-01-01

    Positron emission tomography (PET) imaging reporter genes, such as HSV1-tk and D 2 receptor genes, make it possible to visualise gene expression non-invasively and repetitively in vivo. However, these systems require the synthesis of complicated substrates and the availability of expensive PET equipment. Expression of the sodium/iodide symporter (NIS) gene can be easily monitored with radioiodines and technetium-99m using a gamma camera. To evaluate the possibility of using NIS as an imaging reporter gene, we compared its characteristics with those of the conventional HSV1-tk gene. The CM cell line was made by transfecting the HSV1-tk gene into CT-26 (mouse colon carcinoma cell line). The CTN and CMN cell lines were then made by transfecting the NIS gene into CT-26 and CM. We measured the uptake of iodine-125 iodovinyldeoxyuridine ([ 125 I]IVDU) and 125 I to evaluate the expression of the HSV1-tk and NIS genes, respectively. Each cell line was injected into four flank sites in Balb/c mice. The biodistribution study was performed after intravenously injecting [ 125 I]IVDU and 131 I, and 131 I scintigraphy was performed for the evaluation of NIS expression. In vitro studies indicated that CTN and CMN had 40- to 79-fold and 150- to 256-fold higher uptake of 125 I than CT-26 and CM, respectively. Furthermore, CM and CMN showed 57- to 69-fold higher uptake of [ 125 I]IVDU than CT-26 and CTN. NIS gene expression and 125 I accumulation were found to be directly correlated (R 2 =0.923), as were HSV1-tk gene expression and [ 125 I]IVDU accumulation (R 2 =0.956). Calculated signal per unit NIS and HSV1-tk mRNA expression was 23,240±3,755 cpm and 34,039±5,346 cpm, respectively. In vivo study indicated that CTN and CMN had 2.3- and 5.8-fold higher uptake of 131 I than CT-26 and CM, and 1.8- and 3.5-fold higher uptake of [ 125 I]IVDU than CT-26 and CTN. Scintigraphy using 131 I easily visualised CTN and CMN tumours. In conclusion, the NIS gene may be viewed as an imaging

  13. Imaging of human sodium-iodide symporter gene expression mediated by recombinant adenovirus in skeletal muscle of living rats

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hyun Suk; Park, Seong-Wook [Department of Internal Medicine (Cardiology), Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, 138-736, Seoul (Korea); Lee, Heuiran; Kim, Sung Jin [Department of Microbiology, University of Ulsan College of Medicine, Seoul (Korea); Lee, Won Woo [Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam (Korea); Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea); Yang, You-Jung; Moon, Dae Hyuk [Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea)

    2004-09-01

    We evaluated the feasibility of non-invasive imaging of recombinant adenovirus-mediated human sodium-iodide symporter (hNIS) gene expression by {sup 99m}TcO{sub 4}{sup -} scintigraphy in skeletal muscle of rats. Replication-defective recombinant adenovirus encoding hNIS gene [Rad-CMV-hNIS 5 x 10{sup 7}, 2 x 10{sup 8} or 1 x 10{sup 9} plaque forming units (pfu)] or {beta}-galactosidase gene (Rad-CMV-LacZ 1 x 10{sup 9} pfu) was injected into the right biceps femoris muscle of rats (n=5-6 for each group). Three days after gene transfer, scintigraphy was performed using a gamma camera 30 min after injection of {sup 99m}TcO{sub 4}{sup -} (1.85 MBq). An additional two rats injected with 1 x 10{sup 9} pfu of Rad-CMV-hNIS underwent {sup 99m}TcO{sub 4}{sup -} scintigraphy with sodium perchlorate. After the imaging studies, rats were sacrificed for assessment of the biodistribution of {sup 99m}TcO{sub 4}{sup -} and measurement of hNIS mRNA expression. In all the rats injected with 1 x 10{sup 9} pfu of Rad-CMV-hNIS, hNIS expression was successfully imaged by {sup 99m}TcO{sub 4}{sup -} scintigraphy, while rats injected with Rad-CMV-LacZ or lower doses of Rad-CMV-hNIS failed to show uptake. The biodistribution studies indicated that a significantly different amount of {sup 99m}TcO{sub 4}{sup -} was retained in the liver (p<0.001) and the right muscle (p<0.05), with the highest uptake in rats injected with 1 x 10{sup 9} pfu of Rad-CMV-hNIS. The muscular hNIS mRNA level quantified by real-time reverse transcription-polymerase chain reaction was significantly higher in rats injected with 1 x 10{sup 9} pfu of Rad-CMV-hNIS (p<0.05), with a positive correlation with the imaging counts (r=0.810, p<0.05) and the biodistribution (r=0.847, p<0.001). Hot spots in rats injected with 1 x 10{sup 9} pfu of Rad-CMV-hNIS were specifically inhibited by sodium perchlorate. This study illustrated that {sup 99m}TcO{sub 4}{sup -} scintigraphy can monitor Rad-CMV-hNIS-mediated gene expression in

  14. The feasibility of using a baculovirus vector to deliver the sodium-iodide symporter gene as a reporter

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Xiang; Li Biao; Wang Jun; Yin Hongyan [Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025 (China); Zhang Yifan [Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025 (China)], E-mail: zhangyifan1992@yahoo.com.cn

    2010-04-15

    Purpose: To evaluate the efficiency of baculovirus vectors in transducing FTC-133 cells and to examine the feasibility of using baculovirus vectors for the delivery of the sodium-iodide symporter (NIS) gene as a reporter through co-transduction to monitor the expression of the target gene. Method: Two recombinant baculoviruses were constructed to express NIS and green fluorescent protein (GFP) respectively. FTC-133, 8050C, SW1116, A549 cells, were infected with Bac-GFP. The infection efficiency of Bac-GFP and the intensity of fluorescence, in either the presence or absence of sodium butyrate, were monitored by flow cytometry. The iodine uptake by FTC-133 cells infected with Bac-NIS was measured using a {gamma} counter. FTC-133 cells were infected with a mixture of equal amounts of Bac-NIS and Bac-GFP at different setting of multiplicity of infection (MOI). The changes of GFP fluorescence intensity and iodine uptake were monitored 24 h after infection in the coinfected cells. Results: We have successfully constructed recombinant baculoviruses carrying NIS and GFP under the control of the cytomegalovirus IE-1 promoter. We found that transduced efficiency of baculovirus in 8505C, SW1116, A549 cells are low in absence of sodium butyrate. Yet Bac-GFP infects FTC-133 cells at a high efficiency, 77.67%, 85.57% and 93.23% with MOI of 100, 200 and 400, respectively. The fluorescence intensity of the Bac-GFP infected tumor cells correlated positively with the MOI of the virus. Sodium butyrate induction increased both the infection efficiency and the fluorescence intensity, but increase of infection efficiency was insignificant in FTC-133 cells. Reporter gene (GFP) expression in FTC-133 is stable within 7 days after infection. The radioactivity incorporated by the tumor cells infected with Bac-NIS correlated positively with the MOI of Bac-NIS as well. In tumor cells co-infected with Bac-NIS and Bac-GFP, the amount of radioactivity incorporated significantly correlated with

  15. Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT

    Science.gov (United States)

    Hu, Nien-Jen; Iwata, So; Cameron, Alexander D.; Drew, David

    2011-01-01

    High cholesterol levels greatly increase the risk of cardiovascular disease. By its conversion into bile acids, about 50% of cholesterol is eliminated from the body. However bile acids released from the bile duct are constantly recycled, being reabsorbed in the intestine via the Apical Sodium dependent Bile acid Transporter (ASBT). It has been shown in animal models that plasma cholesterol levels are significantly lowered by specific inhibitors of ASBT1,2, thus ASBT is a target for hypercholesterolemia drugs. Here, we describe the crystal structure of a bacterial homologue of ASBT from Neisseria meningitidis (ASBTNM) at 2.2Å. ASBTNM contains two inverted structural repeats of five transmembrane helices. A Core domain of six helices harbours two sodium ions while the remaining helices form a Panel-like domain. Overall the architecture of the protein is remarkably similar to the sodium-proton antiporter NhaA3 despite no detectable sequence homology. A bile acid molecule is situated between the Core and Panel domains in a large hydrophobic cavity. Residues near to this cavity have been shown to affect the binding of specific inhibitors of human ASBT4. The position of the bile acid together with the molecular architecture suggests the rudiments of a possible transport mechanism. PMID:21976025

  16. The nucleobase cation symporter 1 of Chlamydomonas reinhardtii and that of the evolutionarily distant Arabidopsis thaliana display parallel function and establish a plant-specific solute transport profile.

    Science.gov (United States)

    Schein, Jessica R; Hunt, Kevin A; Minton, Janet A; Schultes, Neil P; Mourad, George S

    2013-09-01

    The single cell alga Chlamydomonas reinhardtii is capable of importing purines as nitrogen sources. An analysis of the annotated C. reinhardtii genome reveals at least three distinct gene families encoding for known nucleobase transporters. In this study the solute transport and binding properties for the lone C. reinhardtii nucleobase cation symporter 1 (CrNCS1) are determined through heterologous expression in Saccharomyces cerevisiae. CrNCS1 acts as a transporter of adenine, guanine, uracil and allantoin, sharing similar - but not identical - solute recognition specificity with the evolutionary distant NCS1 from Arabidopsis thaliana. The results suggest that the solute specificity for plant NCS1 occurred early in plant evolution and are distinct from solute transport specificities of single cell fungal NCS1 proteins. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  17. Sterol regulatory element-binding proteins are regulators of the sodium/iodide symporter in mammary epithelial cells.

    Science.gov (United States)

    Wen, G; Pachner, L I; Gessner, D K; Eder, K; Ringseis, R

    2016-11-01

    The sodium/iodide symporter (NIS), which is essential for iodide concentration in the thyroid, is reported to be transcriptionally regulated by sterol regulatory element-binding proteins (SREBP) in rat FRTL-5 thyrocytes. The SREBP are strongly activated after parturition and throughout lactation in the mammary gland of cattle and are important for mammary epithelial cell synthesis of milk lipids. In this study, we tested the hypothesis that the NIS gene is regulated also by SREBP in mammary epithelial cells, in which NIS is functionally expressed during lactation. Regulation of NIS expression and iodide uptake was investigated by means of inhibition, silencing, and overexpression of SREBP and by reporter gene and DNA-binding assays. As a mammary epithelial cell model, the human MCF-7 cell line, a breast adenocarcinoma cell line, which shows inducible expression of NIS by all-trans retinoic acid (ATRA), and unlike bovine mammary epithelial cells, is widely used to investigate the regulation of mammary gland NIS and NIS-specific iodide uptake, was used. Inhibition of SREBP maturation by treatment with 25-hydroxycholesterol (5 µM) for 48h reduced ATRA (1 µM)-induced mRNA concentration of NIS and iodide uptake in MCF-7 cells by approximately 20%. Knockdown of SREBP-1c and SREBP-2 by RNA interference decreased the mRNA and protein concentration of NIS by 30 to 50% 48h after initiating knockdown, whereas overexpression of nuclear SREBP (nSREBP)-1c and nSREBP-2 increased the expression of NIS in MCF-7 cells by 45 to 60%, respectively, 48h after initiating overexpression. Reporter gene experiments with varying length of NIS promoter reporter constructs revealed that the NIS 5'-flanking region is activated by nSREBP-1c and nSREBP-2 approximately 1.5- and 4.5-fold, respectively, and activation involves a SREBP-binding motif (SRE) at -38 relative to the transcription start site of the NIS gene. Gel shift assays using oligonucleotides spanning either the wild-type or the

  18. Interactions between bicarbonate, potassium, and magnesium, and sulfur-dependent induction of luminescence in Vibrio fischeri.

    Science.gov (United States)

    Tabei, Yosuke; Era, Mariko; Ogawa, Akane; Morita, Hiroshi

    2012-06-01

    In spite of its central importance in research efforts, the relationship between seawater compounds and bacterial luminescence has not previously been investigated in detail. Thus, in this study, we investigated the effect of cations (Na(+) , K(+) , NH(4) (+) , Mg(2+) , and Ca(2+) ) and anions (Cl(-) , HCO(3) (-) , CO(3) (2-) , and NO(3) (-) ) on the induction of both inorganic (sulfate, sulfite, and thiosulfate) and organic (L-cysteine and L-cystine) sulfur-dependent luminescence in Vibrio fischeri. We found that HCO(3) (-) (bicarbonate) and CO(3) (2-) (carbonate), in the form of various compounds, had a stimulatory effect on sulfur-dependent luminescence. The luminescence induced by bicarbonate was further promoted by the addition of magnesium. Potassium also increased sulfur-dependent luminescence when sulfate or thiosulfate was supplied as the sole sulfur source, but not when sulfite, L-cysteine, or L-cystine was supplied. The positive effect of potassium was accelerated by the addition of magnesium and/or calcium. Furthermore, the additional supply of magnesium improved the induction of sulfite- or L-cysteine-dependent luminescence, but not the l-cystine-dependent type. These results suggest that sulfur-dependent luminescence of V. fischeri under nutrient-starved conditions is mainly controlled by bicarbonate, carbonate, and potassium. In addition, our results indicate that an additional supply of magnesium is effective for increasing V. fischeri luminescence. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Evaluation of Lentiviral-Mediated Expression of Sodium Iodide Symporter in Anaplastic Thyroid Cancer and the Efficacy of In Vivo Imaging and Therapy

    Directory of Open Access Journals (Sweden)

    Chien-Chih Ke

    2011-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to 131I therapy due to loss of sodium iodide symporter (NIS gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of 131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy.

  20. Two siblings with early infantile myoclonic encephalopathy due to mutation in the gene encoding mitochondrial glutamate/H+ symporter SLC25A22.

    Science.gov (United States)

    Cohen, Rony; Basel-Vanagaite, Lina; Goldberg-Stern, Hadassah; Halevy, Ayelet; Shuper, Avinoam; Feingold-Zadok, Michal; Behar, Doron M; Straussberg, Rachel

    2014-11-01

    To characterize a new subset of early myoclonic encephalopathy usually associated with metabolic etiologies with a new genetic entity. We describe two siblings with early myoclonic encephalopathy born to consanguineous parents of Arab Muslim origin from Israel. We used homozygosity mapping and candidate gene sequencing to reveal the genetic basis of the myoclonic syndrome. We found a rare missense mutation in the gene encoding one of the two mitochondrial glutamate/H symporters, SLC25A22. The phenotype of early myoclonic encephalopathy was first linked to the same mutation in 2005 in patients of the same ethnicity as our family. Owing to the devastating nature of this encephalopathy, we focus attention on its clinical history, epileptic semiology, distinct electroencephalography features, and genetic basis. We provide the evidence that an integrated diagnostic strategy combining homozygosity mapping with candidate gene sequencing is efficient in consanguineous families with highly heterogeneous autosomal recessive diseases. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  1. High-Throughput Screening and Quantitative Chemical Ranking for Sodium-Iodide Symporter Inhibitors in ToxCast Phase I Chemical Library.

    Science.gov (United States)

    Wang, Jun; Hallinger, Daniel R; Murr, Ashley S; Buckalew, Angela R; Simmons, Steven O; Laws, Susan C; Stoker, Tammy E

    2018-05-01

    Thyroid uptake of iodide via the sodium-iodide symporter (NIS) is the first step in the biosynthesis of thyroid hormones that are critical for health and development in humans and wildlife. Despite having long been a known target of endocrine disrupting chemicals such as perchlorate, information regarding NIS inhibition activity is still unavailable for the vast majority of environmental chemicals. This study applied a previously validated high-throughput approach to screen for NIS inhibitors in the ToxCast phase I library, representing 293 important environmental chemicals. Here 310 blinded samples were screened in a tiered-approach using an initial single-concentration (100 μM) radioactive-iodide uptake (RAIU) assay, followed by 169 samples further evaluated in multi-concentration (0.001 μM-100 μM) testing in parallel RAIU and cell viability assays. A novel chemical ranking system that incorporates multi-concentration RAIU and cytotoxicity responses was also developed as a standardized method for chemical prioritization in current and future screenings. Representative chemical responses and thyroid effects of high-ranking chemicals are further discussed. This study significantly expands current knowledge of NIS inhibition potential in environmental chemicals and provides critical support to U.S. EPA's Endocrine Disruptor Screening Program (EDSP) initiative to expand coverage of thyroid molecular targets, as well as the development of thyroid adverse outcome pathways (AOPs).

  2. Enhanced iodide sequestration by 3-biphenyl-5,6-dihydroimidazo 2,1-b thiazole in sodium/iodide sym-porter (NIS)-expressing cells

    International Nuclear Information System (INIS)

    Lecat-Guillet, N.; Ambroise, Y.

    2008-01-01

    The ability of the sodium/iodide sym-porter (NIS) to take up iodide has long provided the basis for cyto-reductive gene therapy and cancer treatment with radio-iodide. One of the major limitations of this approach is that radio-iodide retention in NIS-expressing cells is not sufficient for their destruction. We identified and characterized a small organic molecule capable of increasing iodide retention in HEK293 cells permanently transfected with human NIS cDNA (hNIS-HEK293) and in the rat thyroid-derived cell line FRTL-5. In the presence of 3-biphenyl-4'-yl-5,6-dihydroimidazo[2,1-b)thiazole (ISA1), the transmembrane iodide concentration gradient was increased up to 4.5-fold. Our experiments indicate that the imidazo-thiazole derivative acts either by inhibiting anion efflux mechanisms, or by promoting the relocation of iodide into subcellular compartments. This new compound is not only an attractive chemical tool to investigate the mechanisms of iodide flux at the cellular level, but also opens promising perspectives in the treatment of cancer after NIS gene transfer. (authors)

  3. Synthesis and biological evaluation of [18F]tetrafluoroborate: a PET imaging agent for thyroid disease and reporter gene imaging of the sodium/iodide symporter

    International Nuclear Information System (INIS)

    Jauregui-Osoro, Maite; Sunassee, Kavitha; Weeks, Amanda J.; Berry, David J.; Paul, Rowena L.; Cleij, Marcel; O'Doherty, Michael J.; Marsden, Paul K.; Szanda, Istvan; Blower, Philip J.; Banga, Jasvinder Paul; Clarke, Susan E.M.; Ballinger, James R.; Cheng, Sheue-Yann

    2010-01-01

    The human sodium/iodide symporter (hNIS) is a well-established target in thyroid disease and reporter gene imaging using gamma emitters 123 I-iodide, 131 I-iodide and 99m Tc-pertechnetate. However, no PET imaging agent is routinely available. The aim of this study was to prepare and evaluate 18 F-labelled tetrafluoroborate ([ 18 F]TFB) for PET imaging of hNIS. [ 18 F]TFB was prepared by isotopic exchange of BF 4 - with [ 18 F]fluoride in hot hydrochloric acid and purified using an alumina column. Its identity, purity and stability in serum were determined by HPLC, thin-layer chromatography (TLC) and mass spectrometry. Its interaction with NIS was assessed in vitro using FRTL-5 rat thyroid cells, with and without stimulation by thyroid-stimulating hormone (TSH), in the presence and absence of perchlorate. Biodistribution and PET imaging studies were performed using BALB/c mice, with and without perchlorate inhibition. [ 18 F]TFB was readily prepared with specific activity of 10 GBq/mg. It showed rapid accumulation in FRTL-5 cells that was stimulated by TSH and inhibited by perchlorate, and rapid specific accumulation in vivo in thyroid (SUV = 72 after 1 h) and stomach that was inhibited 95% by perchlorate. [ 18 F]TFB is an easily prepared PET imaging agent for rodent NIS and should be evaluated for hNIS PET imaging in humans. (orig.)

  4. Selective Adsorption of Uranium (VI) on NaHCO 3 Leached ...

    African Journals Online (AJOL)

    Ion imprinted nano-magnetic composite polymers for selective removal of hexavalent uranium were prepared by a precipitation polymerization technique in the presence of γ-methacryloxypropyltrimethoxysilane (γ-MPS) coated magnetite and other pre-polymerization reagents. The synthesized magnetic polymers were then ...

  5. A combined transcutaneous PO2-PCO2 electrode with electrochemical HCO3- stabilization.

    Science.gov (United States)

    Severinghaus, J W

    1981-10-01

    Combined transcutaneous PO2-PCO2 electrodes are described in which the interaction between the two electrodes due to OH- production at the O2 cathode has been eliminated. An anode of either anodized aluminum or platinum has been driven at a current equal to cathode current to force stoichiometric consumption of OH- at its rate of production. The AgCl reference electrode operates at zero current. O2 sensitivity was not significantly altered by electrolyte pH variation from 6.7 to 9.0 with variations by PCO2. These electrodes have been found stable both with and without spacers, and with electrolytes dissolved in 50-100% ethylene glycol. In 22 anesthetized patients, with electrode temperature of 43 degrees C (s refers to skin surface, a to arterial blood); PsO2 = 0.52PaO2 + 15 (range 54-300) (r = 0.66; Sy . x = 29.6; n = 46); and PsCO2 = 1.39PaCO2 + 2.1 (range 24-98) (r = 0.99; Sy . x = 2.28; n = 48).

  6. Saccharomyces cerevisiae glycerol/H+ symporter Stl1p is essential for cold/near-freeze and freeze stress adaptation. A simple recipe with high biotechnological potential is given

    Directory of Open Access Journals (Sweden)

    Ferreira Célia

    2010-11-01

    Full Text Available Abstract Background Freezing is an increasingly important means of preservation and storage of microbial strains used for many types of industrial applications including food processing. However, the yeast mechanisms of tolerance and sensitivity to freeze or near-freeze stress are still poorly understood. More knowledge on this regard would improve their biotechnological potential. Glycerol, in particular intracellular glycerol, has been assigned as a cryoprotectant, also important for cold/near-freeze stress adaptation. The S. cerevisiae glycerol active transporter Stl1p plays an important role on the fast accumulation of glycerol. This gene is expressed under gluconeogenic conditions, under osmotic shock and stress, as well as under high temperatures. Results We found that cells grown on STL1 induction medium (YPGE and subjected to cold/near-freeze stress, displayed an extremely high expression of this gene, also visible at glycerol/H+ symporter activity level. Under the same conditions, the strains harbouring this transporter accumulated more than 400 mM glycerol, whereas the glycerol/H+ symporter mutant presented less than 1 mM. Consistently, the strains able to accumulate glycerol survive 25-50% more than the stl1Δ mutant. Conclusions In this work, we report the contribution of the glycerol/H+ symporter Stl1p for the accumulation and maintenance of glycerol intracellular levels, and consequently cell survival at cold/near-freeze and freeze temperatures. These findings have a high biotechnological impact, as they show that any S. cerevisiae strain already in use can become more resistant to cold/freeze-thaw stress just by simply adding glycerol to the broth. The combination of low temperatures with extracellular glycerol will induce the transporter Stl1p. This solution avoids the use of transgenic strains, in particular in food industry.

  7. Molecular and structural characterisation of the human sodium/iodide symporter (h N.I.S.) C-terminus and the implication of this domain in the transporter regulation

    International Nuclear Information System (INIS)

    Huc, S.

    2007-12-01

    The human natrium iodide symporter (h N.I.S.) is an intrinsic membrane protein expressed in thyroid cells where it allows iodide uptake and accumulation. It is composed of thirteen transmembrane helices and its ninety- three amino acids long cytosolic C-terminus presents many potential post-translational regulatory sites. A first part of the PhD work has been dedicated to the expression in a bacterial system and to the purification of the cytosolic C-terminal fragment. Biochemical and structural characterisation have revealed that this C-terminus is very flexible but prone to dimerization. The fragment has also been used as a bait to test the interactions with PDZ domain proteins spotted on a membrane. Several proteins interacting with the (natrium/iodide symporter) N.I.S. C-terminus have thus been identified and the study of their implication in the protein regulation has been initiated. A second part of the work has underlined the existence of a N.I.S. fragment co-purified with the entire protein. This fragment has been found in cells in culture stably expressing N.I.S. and also in human thyroid extracts and in rodent thyroid cells. We observed that this fragment is spontaneously associated with the entire protein. It is composed of the last 131 amino acid of the protein and so comprises the last transmembrane domain and the C-terminal extremity. The expression of a truncated form of h N.I.S., lacking the last 131 amino acids, shows that this protein is not correctly addressed to the cell membrane and cells expressing this mutated symporter cannot accumulate iodide. However, our results show that the co-expression of the two N.I.S. parts, the truncated form lacking the last 131 amino acid, and the complementary C-terminal fragment, leads to cells presenting 10 % of the activity of cells expressing the whole N.I.S.. (author)

  8. Imaging of adenovirus-mediated expression of human sodium iodide symporter (hNIS) by 99mTcO4 scan in mice

    International Nuclear Information System (INIS)

    Lee, Won Woo; Moon, D. H.; Park, S. Y.; Jin, J.; Kim, S. J.; Lee, H.

    2002-01-01

    We have evaluated the feasibility of human sodium iodide symporter (hNIS) as a reporter gene by 99m TcO 4 scan in vivo. Recombinant adenovirus encoding hNIS (Rad-hNIS) gene was introduced to FRO cell. hNIS expression was assessed by western blot and 99m TcO 4 uptake in vitro. 99m TcO 4 scan were obtained in BALB/c mice 48 hrs post injection of Tris buffer, Rad-hNIS (1x10 9 or 2x10 8 pfu), or Rad-LacZ (1x10 9 pfu) via the tail vein (n=5-7 for each group). Biodistribution study and RT-PCR were performed. A series of 99m TcO 4 scans were obtained in 2 mice until 21 days post Rad-hNIS injection. FRO readily expressed hNIS protein and incorporated significantly higher level of 99m TcO 4 in vitro. With 99m TcO 4 scan, prominent hepatic uptake was observed only in the mice with 1x10 9 pfu of Rad-hNIS. Liver/lung ratio was increased in this group from 15 (5.7±2.5) till 60 min(6.7±3.6) (p 99m TcO 4 uptake (22.7±11.2 %ID/g) and hNIS mRNA expression were exclusively noticed in livers of this group. The persistent hepatic uptake was observed for up one week. NaClO 4 inhibited the hepatic uptake of 99m TcO 4 . hNIS holds a promising potential as an effective reporter gene for noninvasive/repeated imaging in combination with 99m TcO 4

  9. In vitro radionuclide therapy and in vivo scintigraphic imaging of alpha fetoprotein producing hepatocellular carcinoma by targeted sodium iodide symporter gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kwang Il; Lee, Yong Jin; Lee, Tae Sup; Song, Inho; Cheon, Gi Jeong; Lim, Sang Moo; Kang, Joo Hyun [Korea Institute of Radiological and Medical and Medical Sciences, Seoul (Korea, Republic of); Chung, June Key [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2012-03-15

    This study aimed to develop a gene expression targeting method for specific imaging and therapy of alpha fetoprotein (AFP) producing hepatocellular carcinoma (HCC) cells, using an adenovirus vector containing the human sodium/iodide symporter (hNIS) gene driven by an AFP enhancer/promoter. The recombinant adenovirus vector, AdAFPhNIS (containing the hNIS gene driven by human AFP enhancer/promoter) was prepared. After in vitro infection by the adenovirus, hNIS gene expression in AFP producing cells and in AFP nonproducing cells was investigated using {sup 125}I uptake assay and semi quantitative reverse transcription polymerase chain reaction (RT-PCR). The killing effect of {sup 131}I vitro clonogenic assay. In addition, tumor bearing mice were intravenously injected with the adenovirus, and scintigraphic images were obtained. The expression of hNIS was efficiently demonstrated by {sup 125}I uptake assay in AFP producing cells, but not in AFP nonproducing cells. AFP producing HCC targeted gene expression was confirmed at the mRNA level. Furthermore, in vitro clonogenic assay showed that hNIS gene expression induced by AdAFPhNIS infection in AFP producing cells caused more sensitivity to {sup 131}I than that in AFP nonproducing cells. Injected intravenously in HuH-7 tumor xenografts mice by adenovirus, the functional hNIS gene expression was confirmed in tumor by in vivo scintigraphic imaging. An AFP producing HCC was targeted with an adenovirus vector containing the hNIS gene using the AFP enhancer/promoter in vitro and in vivo. These findings demonstrate that AFP producing HCC specific molecular imaging and radionuclide gene therapy are feasible using this recombinant adenovirus vector system.

  10. In vitro radionuclide therapy and in vivo scintigraphic imaging of alpha fetoprotein producing hepatocellular carcinoma by targeted sodium iodide symporter gene expression

    International Nuclear Information System (INIS)

    Kim, Kwang Il; Lee, Yong Jin; Lee, Tae Sup; Song, Inho; Cheon, Gi Jeong; Lim, Sang Moo; Kang, Joo Hyun; Chung, June Key

    2012-01-01

    This study aimed to develop a gene expression targeting method for specific imaging and therapy of alpha fetoprotein (AFP) producing hepatocellular carcinoma (HCC) cells, using an adenovirus vector containing the human sodium/iodide symporter (hNIS) gene driven by an AFP enhancer/promoter. The recombinant adenovirus vector, AdAFPhNIS (containing the hNIS gene driven by human AFP enhancer/promoter) was prepared. After in vitro infection by the adenovirus, hNIS gene expression in AFP producing cells and in AFP nonproducing cells was investigated using 125 I uptake assay and semi quantitative reverse transcription polymerase chain reaction (RT-PCR). The killing effect of 131 I vitro clonogenic assay. In addition, tumor bearing mice were intravenously injected with the adenovirus, and scintigraphic images were obtained. The expression of hNIS was efficiently demonstrated by 125 I uptake assay in AFP producing cells, but not in AFP nonproducing cells. AFP producing HCC targeted gene expression was confirmed at the mRNA level. Furthermore, in vitro clonogenic assay showed that hNIS gene expression induced by AdAFPhNIS infection in AFP producing cells caused more sensitivity to 131 I than that in AFP nonproducing cells. Injected intravenously in HuH-7 tumor xenografts mice by adenovirus, the functional hNIS gene expression was confirmed in tumor by in vivo scintigraphic imaging. An AFP producing HCC was targeted with an adenovirus vector containing the hNIS gene using the AFP enhancer/promoter in vitro and in vivo. These findings demonstrate that AFP producing HCC specific molecular imaging and radionuclide gene therapy are feasible using this recombinant adenovirus vector system

  11. Visualization of gene expression in the live subject using the Na/I symporter as a reporter gene: applications in biotherapy.

    Science.gov (United States)

    Baril, Patrick; Martin-Duque, Pilar; Vassaux, Georges

    2010-02-01

    Biotherapies involve the utilization of antibodies, genetically modified viruses, bacteria or cells for therapeutic purposes. Molecular imaging has the potential to provide unique information that will guarantee their biosafety in humans and provide a rationale for the future development of new generations of reagents. In this context, non-invasive imaging of gene expression is an attractive prospect, allowing precise, spacio-temporal measurements of gene expression in longitudinal studies involving gene transfer vectors. With the emergence of cell therapies in regenerative medicine, it is also possible to track cells injected into subjects. In this context, the Na/I symporter (NIS) has been used in preclinical studies. Associated with a relevant radiotracer ((123)I(-), (124)I(-), (99m)TcO4(-)), NIS can be used to monitor gene transfer and the spread of selectively replicative viruses in tumours as well as in cells with a therapeutic potential. In addition to its imaging potential, NIS can be used as a therapeutic transgene through its ability to concentrate therapeutic doses of radionuclides in target cells. This dual property has applications in cancer treatment and could also be used to eradicate cells with therapeutic potential in the case of adverse events. Through experience acquired in preclinical studies, we can expect that non-invasive molecular imaging using NIS as a transgene will be pivotal for monitoring in vivo the exact distribution and pharmacodynamics of gene expression in a precise and quantitative way. This review highlights the applications of NIS in biotherapy, with a particular emphasis on image-guided radiotherapy, monitoring of gene and vector biodistribution and trafficking of stem cells.

  12. Establishment of a hepatocellular carcinoma cell line expressing dual reporter genes: sodium iodide symporter (NIS) and enhanced green fluorescence protein (EGFP)

    International Nuclear Information System (INIS)

    Kwak, Won Jung; Koo, Bon Chul; Kwon, Mo Sun

    2007-01-01

    Dual reporter gene imaging has several advantages for more sophisticated molecular imaging studies such as gene therapy monitoring. Herein, we have constructed hepatoma cell line expressing dual reporter genes of sodium iodide symporter (NIS) and enhanced green fluorescence protein (EGFP), and the functionalities of the genes were evaluated in vivo by nuclear and optical imaging. A pRetro-PN vector was constructed after separating NIS gene from pcDNA-NIS. RSV-EGFP-WPRE fragment separated from pLNRGW was cloned into pRetro-PN vector. The final vector expressing dual reporter genes was named pRetro-PNRGW. A human hepatoma (HepG2) cells were transfected by the retrovirus containing NIS and EGFP gene (HepG2-NE). Expression of NIS gene was confirmed by RT-PCR, radioiodine uptake and efflux studies. Expression of EGFP was confirmed by RT-PCR and fluorescence microscope. The HepG2 and HepG2-NE cells were implanted in shoulder and hindlimb of nude mice, then fluorescence image, gamma camera image and I-124 microPET image were undertaken. The HepG2-NE cell was successfully constructed. RT-PCR showed NIS and EGFP mRNA expression. About 50% of cells showed fluorescence. The iodine uptake of NIS-expressed cells was about 9 times higher than control. In efflux study, T 1/2 of HepG2-NE cells was 9 min. HepG2-NE xenograft showed high signal-to-background fluorescent spots and higher iodine-uptake compared to those of HepG2 xenograft. A hepatoma cell line expressing NIS and EGFP dual reporter genes was successfully constructed and could be used as a potential either by therapeutic gene or imaging reporter gene

  13. Expression of the Na+/l- symporter (NIS is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus

    Directory of Open Access Journals (Sweden)

    Wapnir Irene L

    2007-01-01

    Full Text Available Abstract Background The sodium/iodide symporter (NIS is a plasma membrane glycoprotein that mediates iodide (I- transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract. Methods Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients. Results Regarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps. Conclusion That NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease.

  14. Synthesis and biological evaluation of [{sup 18}F]tetrafluoroborate: a PET imaging agent for thyroid disease and reporter gene imaging of the sodium/iodide symporter

    Energy Technology Data Exchange (ETDEWEB)

    Jauregui-Osoro, Maite; Sunassee, Kavitha; Weeks, Amanda J.; Berry, David J.; Paul, Rowena L.; Cleij, Marcel; O' Doherty, Michael J.; Marsden, Paul K.; Szanda, Istvan; Blower, Philip J. [King' s College London, Division of Imaging Sciences, London (United Kingdom); Banga, Jasvinder Paul [King' s College London, Division of Cell and Gene Based Therapy, London (United Kingdom); Clarke, Susan E.M.; Ballinger, James R. [Guy' s and St Thomas' NHS Trust, Department of Nuclear Medicine, London (United Kingdom); Cheng, Sheue-Yann [National Cancer Institute, Laboratory of Molecular Biology, Bethesda (United States)

    2010-11-15

    The human sodium/iodide symporter (hNIS) is a well-established target in thyroid disease and reporter gene imaging using gamma emitters {sup 123}I-iodide, {sup 131}I-iodide and {sup 99m}Tc-pertechnetate. However, no PET imaging agent is routinely available. The aim of this study was to prepare and evaluate {sup 18}F-labelled tetrafluoroborate ([{sup 18}F]TFB) for PET imaging of hNIS. [{sup 18}F]TFB was prepared by isotopic exchange of BF{sub 4} {sup -} with [{sup 18}F]fluoride in hot hydrochloric acid and purified using an alumina column. Its identity, purity and stability in serum were determined by HPLC, thin-layer chromatography (TLC) and mass spectrometry. Its interaction with NIS was assessed in vitro using FRTL-5 rat thyroid cells, with and without stimulation by thyroid-stimulating hormone (TSH), in the presence and absence of perchlorate. Biodistribution and PET imaging studies were performed using BALB/c mice, with and without perchlorate inhibition. [{sup 18}F]TFB was readily prepared with specific activity of 10 GBq/mg. It showed rapid accumulation in FRTL-5 cells that was stimulated by TSH and inhibited by perchlorate, and rapid specific accumulation in vivo in thyroid (SUV = 72 after 1 h) and stomach that was inhibited 95% by perchlorate. [{sup 18}F]TFB is an easily prepared PET imaging agent for rodent NIS and should be evaluated for hNIS PET imaging in humans. (orig.)

  15. Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS.

    Science.gov (United States)

    Kim, Ji Won; Kim, Subin; Kim, Songwon; Lee, Haerim; Lee, Jie-Oh; Jin, Mi Sun

    2017-05-31

    The sodium-dependent citrate transporter of Klebsiella pneumoniae (KpCitS) belongs to the 2-hydroxycarboxylate transporter (2-HCT) family and allows the cell to use citrate as sole carbon and energy source in anaerobic conditions. Here we present crystal structures of KpCitS in citrate-bound outward-facing, citrate-bound asymmetric, and citrate-free inward-facing state. The structures reveal that the KpCitS dimerization domain remains stationary throughout the transport cycle due to a hydrogen bond network as well as extensive hydrophobic interactions. In contrast, its transport domain undergoes a ~35° rigid-body rotation and a ~17 Å translocation perpendicular to the membrane to expose the substrate-binding site alternately to either side of the membrane. Furthermore, homology models of two other 2-HCT proteins based on the KpCitS structure offer structural insights into their differences in substrate specificity at a molecular level. On the basis of our results and previous biochemical data, we propose that the activity of the 2-HCT CitS involves an elevator-like movement in which the transport domain itself traverses the lipid bilayer, carrying the substrate into the cell in a sodium-dependent manner.

  16. Comparison of Human Sodium/Iodide Symporter (hNIS) Gene Expressions between Lentiviral and Adenoviral Vectors in Rat Mesenchymal Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, So Yeon; Lee, Won Woo; Kim, Hyun Joo; Chung, June Key; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Sung Jin; Lee, Heui Ran [Medical Research Center, Seoul National University, Seoul (Korea, Republic of)

    2008-10-15

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirusmediated delivery systems has not been reported. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and transduction efficiency of Rad-hNIS into rMSC evaluated by Rad-GFP was 19.1{+-}4.7%, 54.0{+-}6.4%, 85.7{+-}8.7%, and 98.4{+-}1.3% at MOI 1, 5, 20, and 100, respectively. The hNIS expressions in lenti-hNIS-rMSC or adeno-hNIS-rMSC were assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry and western blot analyses revealed that hNIS expressions in lenti-hNIS-rMSC were greater than those in adeno-hNIS-rMSC at MOI 20 but lower than at MOI 50. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (29,704{+-}6,659 picomole/10{sup 6} cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (6,168{+-}2,134 picomole/10{sup 6} cells). Despite lower amount of expressed protein, hNIS function in rMSC was greater by lentivirus than by adenovirus mediated expression. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative vector efficiency for transgene expression.

  17. Evaluation of the therapeutic efficacy of a VEGFR2-blocking antibody using sodium-iodide symporter molecular imaging in a tumor xenograft model

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, Su-Jin; Lee, Chang-Moon; Kim, Eun-Mi [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Uhm, Tai-Boong [Faculty of Biological Science, Chonbuk National University, Jeonju-si, jeonbuk 561-756 (Korea, Republic of); Jeong, Hwan-Jeong, E-mail: jayjeong@chonbuk.ac.k [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Kim, Dong Wook; Lim, Seok Tae; Sohn, Myung-Hee [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of)

    2011-01-15

    Purpose: Vascular endothelial growth factor receptor 2-blocking antibody (DC101) has inhibitory effects on tumor growth and angiogenesis in vivo. The human sodium/iodide symporter (hNIS) gene has been shown to be a useful molecular imaging reporter gene. Here, we investigated the evaluation of therapeutic efficacy by molecular imaging in reporter gene transfected tumor xenografts using a gamma imaging system. Methods: The hNIS gene was transfected into MDA-MB-231 cells using Lipofectamine. The correlation between the number of MDA-MB-231-hNIS cells and the uptake of {sup 99m}Tc-pertechnetate or {sup 125}I was investigated in vitro by gamma imaging and counting. MDA-MB-231-hNIS cells were injected subcutaneously into mice. When the tumor volume reached 180-200 mm{sup 3}, we randomly assigned five animals to each of three groups representing different tumor therapies; no DC101 (control), 100 {mu}g, or 150 {mu}g DC101/mouse. One week and 2 weeks after the first injection of DC101, gamma imaging was performed. Mice were sacrificed 2 weeks after the first injection of DC101. The tumor tissues were used for reverse transcriptase-polymerase chain reaction (RT-PCR) and CD31 staining. Results: Uptake of {sup 125}I and {sup 99m}Tc-pertechnetate into MDA-MB-231-hNIS cells in vitro showed correlation with the number of cells. In DC101 treatment groups, the mean tumor volume was smaller than that of the control mice. Furthermore, tumor uptake of {sup 125}I was lower than in the controls. The CD31 staining and RT-PCR assay results showed that vessel formation and expression of the hNIS gene were significantly reduced in the tumor tissues of treatment groups. Conclusion: This study demonstrated the power of molecular imaging using a gamma imaging system for evaluating the therapeutic efficacy of an antitumor treatment. Molecular imaging systems may be useful in evaluation and development of effective diagnostic and/or therapeutic antibodies for specific target molecules.

  18. Comparison of Human Sodium/Iodide Symporter (hNIS) Gene Expressions between Lentiviral and Adenoviral Vectors in Rat Mesenchymal Stem Cells

    International Nuclear Information System (INIS)

    Park, So Yeon; Lee, Won Woo; Kim, Hyun Joo; Chung, June Key; Kim, Sang Eun; Kim, Sung Jin; Lee, Heui Ran

    2008-01-01

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirusmediated delivery systems has not been reported. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and transduction efficiency of Rad-hNIS into rMSC evaluated by Rad-GFP was 19.1±4.7%, 54.0±6.4%, 85.7±8.7%, and 98.4±1.3% at MOI 1, 5, 20, and 100, respectively. The hNIS expressions in lenti-hNIS-rMSC or adeno-hNIS-rMSC were assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry and western blot analyses revealed that hNIS expressions in lenti-hNIS-rMSC were greater than those in adeno-hNIS-rMSC at MOI 20 but lower than at MOI 50. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (29,704±6,659 picomole/10 6 cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (6,168±2,134 picomole/10 6 cells). Despite lower amount of expressed protein, hNIS function in rMSC was greater by lentivirus than by adenovirus mediated expression. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative vector efficiency for transgene expression

  19. Imaging of adenovirus-mediated expression of human sodium iodide symporter (hNIS) by {sup 99m}TcO{sub 4} scan in mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Woo; Moon, D. H.; Park, S. Y.; Jin, J.; Kim, S. J.; Lee, H. [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    We have evaluated the feasibility of human sodium iodide symporter (hNIS) as a reporter gene by {sup 99m}TcO{sub 4} scan in vivo. Recombinant adenovirus encoding hNIS (Rad-hNIS) gene was introduced to FRO cell. hNIS expression was assessed by western blot and {sup 99m}TcO{sub 4} uptake in vitro. {sup 99m}TcO{sub 4} scan were obtained in BALB/c mice 48 hrs post injection of Tris buffer, Rad-hNIS (1x10{sup 9} or 2x10{sup 8} pfu), or Rad-LacZ (1x10{sup 9} pfu) via the tail vein (n=5-7 for each group). Biodistribution study and RT-PCR were performed. A series of {sup 99m}TcO{sub 4} scans were obtained in 2 mice until 21 days post Rad-hNIS injection. FRO readily expressed hNIS protein and incorporated significantly higher level of {sup 99m}TcO{sub 4} in vitro. With {sup 99m}TcO{sub 4} scan, prominent hepatic uptake was observed only in the mice with 1x10{sup 9} pfu of Rad-hNIS. Liver/lung ratio was increased in this group from 15 (5.7{+-}2.5) till 60 min(6.7{+-}3.6) (p<0.01). Significantly increased {sup 99m}TcO{sub 4} uptake (22.7{+-}11.2 %ID/g) and hNIS mRNA expression were exclusively noticed in livers of this group. The persistent hepatic uptake was observed for up one week. NaClO{sub 4} inhibited the hepatic uptake of {sup 99m}TcO{sub 4}. hNIS holds a promising potential as an effective reporter gene for noninvasive/repeated imaging in combination with {sup 99m}TcO{sub 4}.

  20. Comparison of human sodium iodide symporter (hNIS) gene expression between lentiviral and adenoviral vectors in rat mesenchymal stem cell

    International Nuclear Information System (INIS)

    Park, So Yeon; Lee, Won Woo; Kim, Sung Jin; Lee, Heui Ran; Kim, Hyun Joo; Chung, June Key; Kim, Sang Eun

    2007-01-01

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirus-mediated delivery systems has not been done. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated stably hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning the hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and Rad-hNIS transduced rMSC (adeno-hNIS-rMSC) was evaluated for the hNIS expression 48 hours post infection at MOI 1, 5, 20, 50, and 100. The hNIS expression in lenti-hNIS-rMSC or adeno-hNIS-rMSC was assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry using mono-clonal anti-hNIS antibody revealed that intensity of hNIS immunoreactivity in lenti-hNIS-rMSC was greater than that in adeno-hNIS-rMSC at MOl 20 but lower than that at MOl 50. Western blot analysis also showed that lenti-hNIS-rMSC was intermediate between adeno-hNIS-rMSCs at MOl 20 and 50 in hNIS expression. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (297046659 picomole/106 cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (61682134 picomole/106 cells). These results suggest that lentivirus mediated hNIS expression is greater in terms of hNIS function but lower in terms of hNIS protein amount than adenovirus mediated hNIS expression 48 hours post infection. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative viral efficiency of transgene expression

  1. Activity-dependent astrocyte swelling is mediated by pH-regulating mechanisms.

    Science.gov (United States)

    Larsen, Brian Roland; MacAulay, Nanna

    2017-10-01

    During neuronal activity in the mammalian brain, the K + released into the synaptic space is initially buffered by the astrocytic compartment. In parallel, the extracellular space (ECS) shrinks, presumably due to astrocytic cell swelling. With the Na + /K + /2Cl - cotransporter and the Kir4.1/AQP4 complex not required for the astrocytic cell swelling in the hippocampus, the molecular mechanisms underlying the activity-dependent ECS shrinkage have remained unresolved. To identify these molecular mechanisms, we employed ion-sensitive microelectrodes to measure changes in ECS, [K + ] o and [H + ] o /pH o during electrical stimulation of rat hippocampal slices. Transporters and receptors responding directly to the K + and glutamate released into the extracellular space (the K + /Cl - cotransporter, KCC, glutamate transporters and G protein-coupled receptors) did not modulate the extracellular space dynamics. The HCO3--transporting mechanism, which in astrocytes mainly constitutes the electrogenic Na + / HCO3- cotransporter 1 (NBCe1), is activated by the K + -mediated depolarization of the astrocytic membrane. Inhibition of this transporter reduced the ECS shrinkage by ∼25% without affecting the K + transients, pointing to NBCe1 as a key contributor to the stimulus-induced astrocytic cell swelling. Inhibition of the monocarboxylate cotransporters (MCT), like-wise, reduced the ECS shrinkage by ∼25% without compromising the K + transients. Isosmotic reduction of extracellular Cl - revealed a requirement for this ion in parts of the ECS shrinkage. Taken together, the stimulus-evoked astrocytic cell swelling does not appear to occur as a direct effect of the K + clearance, as earlier proposed, but partly via the pH-regulating transport mechanisms activated by the K + -induced astrocytic depolarization and the activity-dependent metabolism. © 2017 Wiley Periodicals, Inc.

  2. Effect of secretin and inhibitors of HCO3-/H+ transport on the membrane voltage of rat pancreatic duct cells

    DEFF Research Database (Denmark)

    Novak, I; Pahl, C

    1993-01-01

    depolarized the basolateral membrane voltage, Vbl, by up to 35 mV (n = 37); a half-maximal response was obtained at 3 x 10(-11) mol/l. In unstimulated ducts a decrease in the luminal Cl- concentration (120 to 37 mmol/l) had a marginal effect on Vbl, but after maximal secretin stimulation it evoked a 14 +/- 2......), respectively. The fractional resistance of the basolateral membrane (FRbl) doubled, and the depolarizing responses to changes in bath K+ concentrations (5 to 20 mmol/l) decreased from 22 +/- 1 to 11 +/- 2 mV.(ABSTRACT TRUNCATED AT 250 WORDS)...

  3. Mechanisms of Contrast-Induced Nephropathy Reduction for Saline (NaCl and Sodium Bicarbonate (NaHCO3

    Directory of Open Access Journals (Sweden)

    W. Patrick Burgess

    2014-01-01

    Full Text Available Nephropathy following contrast media (CM exposure is reduced by administration before, during, and after the contrast procedure of either isotonic sodium chloride solution (Saline or isotonic sodium bicarbonate solution (IsoBicarb. The reasons for this reduction are not well established for either sodium salt; probable mechanisms are discussed in this paper. For Saline, the mechanism for the decrease in CIN is likely related primarily to the increased tubular flow rates produced by volume expansion and therefore a decreased concentration of the filtered CM during transit through the kidney tubules. Furthermore, increased tubular flow rates produce a slight increase in tubular pH resulting from a fixed acid excretion in an increased tubular volume. The mechanism for the decreased CIN associated with sodium bicarbonate includes the same mechanisms listed for Saline in addition to a renal pH effect. Increased filtered bicarbonate anion raises both tubular pH and tubular bicarbonate anion levels toward blood physiologic levels, thus providing increased buffer for reactive oxygen species (ROS formed in the tubules as a result of exposure to CM in renal tubular fluid.

  4. Molecular and structural characterisation of the human sodium/iodide symporter (h N.I.S.) C-terminus and the implication of this domain in the transporter regulation; Caracterisation moleculaire et structurale de l'extremite C-Terminale du co-transporteur sodium/iode humain (h N.I.S.): Implication de ce domaine dans la regulation du transporteur

    Energy Technology Data Exchange (ETDEWEB)

    Huc, S

    2007-12-15

    The human natrium iodide symporter (h N.I.S.) is an intrinsic membrane protein expressed in thyroid cells where it allows iodide uptake and accumulation. It is composed of thirteen transmembrane helices and its ninety- three amino acids long cytosolic C-terminus presents many potential post-translational regulatory sites. A first part of the PhD work has been dedicated to the expression in a bacterial system and to the purification of the cytosolic C-terminal fragment. Biochemical and structural characterisation have revealed that this C-terminus is very flexible but prone to dimerization. The fragment has also been used as a bait to test the interactions with PDZ domain proteins spotted on a membrane. Several proteins interacting with the (natrium/iodide symporter) N.I.S. C-terminus have thus been identified and the study of their implication in the protein regulation has been initiated. A second part of the work has underlined the existence of a N.I.S. fragment co-purified with the entire protein. This fragment has been found in cells in culture stably expressing N.I.S. and also in human thyroid extracts and in rodent thyroid cells. We observed that this fragment is spontaneously associated with the entire protein. It is composed of the last 131 amino acid of the protein and so comprises the last transmembrane domain and the C-terminal extremity. The expression of a truncated form of h N.I.S., lacking the last 131 amino acids, shows that this protein is not correctly addressed to the cell membrane and cells expressing this mutated symporter cannot accumulate iodide. However, our results show that the co-expression of the two N.I.S. parts, the truncated form lacking the last 131 amino acid, and the complementary C-terminal fragment, leads to cells presenting 10 % of the activity of cells expressing the whole N.I.S.. (author)

  5. Positive radionuclide imaging of miRNA expression using RILES and the human sodium iodide symporter as reporter gene is feasible and supports a protective role of miRNA-23a in response to muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Viorel Simion

    Full Text Available MicroRNAs (miRNAs are key players in many biological processes and are considered as an emerging class of pharmacology drugs for diagnosis and therapy. However to fully exploit the therapeutic potential of miRNAs, it is becoming crucial to monitor their expression pattern using medical imaging modalities. Recently, we developed a method called RILES, for RNAi-Inducible Luciferase Expression System that relies on an engineered regulatable expression system to switch-ON the expression of the luciferase gene when a miRNA of interest is expressed in cells. Here we investigated whether replacing the luciferase reporter gene with the human sodium iodide symporter (hNIS reporter gene will be also suited to monitor the expression of miRNAs in a clinical setting context. We provide evidence that radionuclide imaging of miRNA expression using hNIS is feasible although it is not as robust as when the luciferase reporter gene is used. However, under appropriate conditions, we monitored the expression of several miRNAs in cells, in the liver and in the tibialis anterior muscle of mice undergoing muscular atrophy. We demonstrated that radiotracer accumulation in transfected cells correlated with the induction of hNIS and with the expression of miRNAs detected by real time PCR. We established the kinetic of miRNA-23a expression in mice and demonstrated that this miRNA follows a biphasic expression pattern characterized by a loss of expression at a late time point of muscular atrophy. At autopsy, we found an opposite expression pattern between miRNA-23a and one of the main transcriptional target of this miRNA, APAF-1, and as downstream target, Caspase 9. Our results report the first positive monitoring of endogenously expressed miRNAs in a nuclear medicine imaging context and support the development of additional work to establish the potential therapeutic value of miRNA-23 to prevent the damaging effects of muscular atrophy.

  6. Positive radionuclide imaging of miRNA expression using RILES and the human sodium iodide symporter as reporter gene is feasible and supports a protective role of miRNA-23a in response to muscular atrophy.

    Science.gov (United States)

    Simion, Viorel; Sobilo, Julien; Clemoncon, Rudy; Natkunarajah, Sharuja; Ezzine, Safia; Abdallah, Florence; Lerondel, Stephanie; Pichon, Chantal; Baril, Patrick

    2017-01-01

    MicroRNAs (miRNAs) are key players in many biological processes and are considered as an emerging class of pharmacology drugs for diagnosis and therapy. However to fully exploit the therapeutic potential of miRNAs, it is becoming crucial to monitor their expression pattern using medical imaging modalities. Recently, we developed a method called RILES, for RNAi-Inducible Luciferase Expression System that relies on an engineered regulatable expression system to switch-ON the expression of the luciferase gene when a miRNA of interest is expressed in cells. Here we investigated whether replacing the luciferase reporter gene with the human sodium iodide symporter (hNIS) reporter gene will be also suited to monitor the expression of miRNAs in a clinical setting context. We provide evidence that radionuclide imaging of miRNA expression using hNIS is feasible although it is not as robust as when the luciferase reporter gene is used. However, under appropriate conditions, we monitored the expression of several miRNAs in cells, in the liver and in the tibialis anterior muscle of mice undergoing muscular atrophy. We demonstrated that radiotracer accumulation in transfected cells correlated with the induction of hNIS and with the expression of miRNAs detected by real time PCR. We established the kinetic of miRNA-23a expression in mice and demonstrated that this miRNA follows a biphasic expression pattern characterized by a loss of expression at a late time point of muscular atrophy. At autopsy, we found an opposite expression pattern between miRNA-23a and one of the main transcriptional target of this miRNA, APAF-1, and as downstream target, Caspase 9. Our results report the first positive monitoring of endogenously expressed miRNAs in a nuclear medicine imaging context and support the development of additional work to establish the potential therapeutic value of miRNA-23 to prevent the damaging effects of muscular atrophy.

  7. Path Dependency

    OpenAIRE

    Mark Setterfield

    2015-01-01

    Path dependency is defined, and three different specific concepts of path dependency – cumulative causation, lock in, and hysteresis – are analyzed. The relationships between path dependency and equilibrium, and path dependency and fundamental uncertainty are also discussed. Finally, a typology of dynamical systems is developed to clarify these relationships.

  8. Clinical value of sodium iodide symporter

    International Nuclear Information System (INIS)

    Li Qian

    2003-01-01

    The sodium iodide symptorter (NIS) is a membrane glycoprotein that mediates iodide uptake in the thyroid gland and several extrathyroidal tissues. In addition to thyroid tissues, the expression of NIS is found in stomach, prostate, placenta and so on. Radioiodine-concentrating activity in thyroid tissues has allowed the use of radioiodine as a diagnostic and therapeutic agent for patients with thyroid disorders. However, some extrathyroid tissues also take up radioiodine, contributing to unwanted side effects of radioiodine therapy. Now that the molecule of NIS has been cloned and characterized, it may be possible to develop novel strategies to differentially modulate NIS expression and activity, enhancing it in target tissues and impeding it in others. It is also important to explore the use of NIS as an imaging reporter gene to monitor the expression profile of the transgene in transgenic mouse animal models and in patients undergoing gene therapy clinical trials

  9. Reversible pH-dependent activation/inactivation of CF(1-ATPase of spinach chloroplasts

    Directory of Open Access Journals (Sweden)

    A. P. Khomochkin

    2017-08-01

    Full Text Available The aim of the work was to study the reverse pH-dependent regulation of the enzymatic activity of the catalytic part of ATP synthase (EC 3.6.3.14 of chloroplast – coupling factor CF1. It was shown that the short-term incubation of isolated CF1 in the media with pH 4.5 or 3.5 leads to inactivation of Ca2+-ATPase, which is rapidly (t1/2 ~ 1 min restored in the medium containing 0.5-10 mM bicarbonate at pH 7.8. After acid treatment, the rate of Mg2+-ATPase reaction was also stimulated in the presence of 1 mM bicarbonate (рН 7.8; 37 °С. The increase in Ca2+– and Mg2+-АТР activity of CF1 associated with the addition of NaHCO3 solution was completely eliminated after the introduction of 50 mM acetazolamide – a specific inhibitor of carbonic anhydrase. The obtained results suggest the existence of the bound bicarbonate in the CF1 structure, which apparently participates in proton transfer.

  10. Dependent Classes

    DEFF Research Database (Denmark)

    Gasiunas, Vaidas; Mezini, Mira; Ostermann, Klaus

    2007-01-01

    of dependent classes and a machine-checked type soundness proof in Isabelle/HOL [29], the first of this kind for a language with virtual classes and path-dependent types. [29] T.Nipkow, L.C. Poulson, and M. Wenzel. Isabelle/HOL -- A Proof Assistant for Higher-Order Logic, volume 2283 of LNCS, Springer, 2002......Virtual classes allow nested classes to be refined in subclasses. In this way nested classes can be seen as dependent abstractions of the objects of the enclosing classes. Expressing dependency via nesting, however, has two limitations: Abstractions that depend on more than one object cannot...... be modeled and a class must know all classes that depend on its objects. This paper presents dependent classes, a generalization of virtual classes that expresses similar semantics by parameterization rather than by nesting. This increases expressivity of class variations as well as the flexibility...

  11. Exercise Dependence

    Directory of Open Access Journals (Sweden)

    Erdal Vardar

    2012-06-01

    Full Text Available Exercise dependence define a condition in which a person performs excessive exercise resulting in deterioration of his or her physical and mental health wellness. Despite many clinical research studies on exercise dependence, exact diagnostic criteria has not been developed yet. Clinical evidences concerning etiology, epidemiology, underlying mechanisms and treatment of exercise dependence are still not sufficient. Moreover, evaluation of this clinical disorder within dependency perspective is a fairly new concept. Recent studies have shown that exercise dependence has similar features like chemical substance dependence with regards to withdrawal and tolerance symptoms. The aim of this review was to briefly evaluate diagnostic and clinical features of exercise dependence. [Archives Medical Review Journal 2012; 21(3.000: 163-173

  12. Heat indicators of oxidative stress, inflammation and metal transport show dependence of cadmium pollution history in the liver of female zebrafish.

    Science.gov (United States)

    Zhu, Qing-Ling; Guo, Sai-Nan; Yuan, Shuang-Shuang; Lv, Zhen-Ming; Zheng, Jia-Lang; Xia, Hu

    2017-10-01

    Environmental stressors such as high temperature and metal exposure may occur sequentially, simultaneously, previously in aquatic ecosystems. However, information about whether responses to high temperature depend on Cd exposure history is still unknown in fish. Zebrafish were exposed to 0 (group 1), 2.5 (group 2) and 5μg/L (group 3) cadmium (Cd) for 10 weeks, and then each group was subjected to Cd-free water maintained at 26°C and 32°C for 7days respectively. 26 indicators were used to compare differences between 26°C and 32°C in the liver of female zebrafish, including 5 biochemical indicators (activity of Cu/Zn-SOD, CAT and iNOS; LPO; MT protein), 8 molecular indicators of oxidative stress (mRNA levels of Nrf2, Cu/Zn-SOD, CAT, HSF1, HSF2, HSP70, MTF-1 and MT), 5 molecular indicators of inflammation (mRNA levels of IL-6, IL-1β, TNF-α, iNOS and NF-κB), 8 molecular indicators of metal transport (mRNA levels of, ZnT1, ZnT5, ZIP8, ZIP10, ATP7A, ATP7B and CTR1). All biochemical indicators were unchanged in group 1 and changed in group 2 and 3. Contrarily, differences were observed in almost all of molecular indicators of inflammation and metal transport in group 1, about half in group 2, and few in group 3. We also found that all molecular indicators of oxidative stress in group 2 and fewer in group 1 and 3 were significantly affected by heat. Our data indicated that heat indicators of oxidative stress, inflammation and metal transport showed dependence of previous cadmium exposure in the liver of zebrafish, emphasizing metal pollution history should be carefully considered when evaluating heat stress in fish. Copyright © 2017. Published by Elsevier B.V.

  13. Dependency Parsing

    CERN Document Server

    Kubler, Sandra; Nivre, Joakim

    2009-01-01

    Dependency-based methods for syntactic parsing have become increasingly popular in natural language processing in recent years. This book gives a thorough introduction to the methods that are most widely used today. After an introduction to dependency grammar and dependency parsing, followed by a formal characterization of the dependency parsing problem, the book surveys the three major classes of parsing models that are in current use: transition-based, graph-based, and grammar-based models. It continues with a chapter on evaluation and one on the comparison of different methods, and it close

  14. [Affective dependency].

    Science.gov (United States)

    Scantamburlo, G; Pitchot, W; Ansseau, M

    2013-01-01

    Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could on neuronal circuits in prefronto-limbic regions that are essential for emotional behaviour.We also focus on the interrelations between dependent personality, domestic violence and addictions. The objective for the clinician is to propose a restoration of self-esteem and therapeutic strategies focused on autonomy.

  15. [Caffeine dependence].

    Science.gov (United States)

    Ogawa, Naoshi; Ueki, Hirofumi

    2010-08-01

    Caffeine is the most widely consumed psychoactive substance in the world and is a legal stimulant that is readily available to children. The potential for dependence on caffeine has been debated. Presently, due to a paucity of clinical evidence on caffeine dependence, no such diagnosis is included in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). Although in recent studies, a subset of the general population was found to demonstrate caffeine dependence. It is valuable for psychiatrists and primary care physicians to recognize caffeine dependence as a clinical syndrome, since some people are distressed by their caffeine use and feel they can not control or stop their problematic use.

  16. Path Dependence

    DEFF Research Database (Denmark)

    Madsen, Mogens Ove

    Begrebet Path Dependence blev oprindelig udviklet inden for New Institutionel Economics af bl.a. David, Arthur og North. Begrebet har spredt sig vidt i samfundsvidenskaberne og undergået en udvikling. Dette paper propagerer for at der er sket så en så omfattende udvikling af begrebet, at man nu kan...... tale om 1. og 2. generation af Path Dependence begrebet. Den nyeste udvikling af begrebet har relevans for metodologi-diskusionerne i relation til Keynes...

  17. Na+,HCO3--cotransport is functionally upregulated during human breast carcinogenesis and required for the inverted pH gradient across the plasma membrane

    DEFF Research Database (Denmark)

    Lee, Soojung; Mele, Marco; Vahl, Pernille

    2015-01-01

    Metabolic and biochemical changes during breast carcinogenesis enhance cellular acid production. Extrusion of the acid load from the cancer cells raises intracellular pH, while it decreases extracellular pH creating an inverted pH gradient across the plasma membrane compared to normal cells and p...

  18. Na+, HCO3--cotransporter NBCn1 increases pHi gradients, filopodia, and migration of smooth muscle cells and promotes arterial remodelling.

    Science.gov (United States)

    Boedtkjer, Ebbe; Bentzon, Jacob F; Dam, Vibeke S; Aalkjaer, Christian

    2016-08-01

    Arterial remodelling can cause luminal narrowing and obstruct blood flow. We tested the hypothesis that cellular acid-base transport facilitates proliferation and migration of vascular smooth muscle cells (VSMCs) and enhances remodelling of conduit arteries. [Formula: see text]-cotransport via NBCn1 (Slc4a7) mediates net acid extrusion and controls steady-state intracellular pH (pHi) in VSMCs of mouse carotid arteries and primary aortic explants. Carotid arteries undergo hypertrophic inward remodelling in response to partial or complete ligation in vivo, but the increase in media area and thickness and reduction in lumen diameter are attenuated in arteries from NBCn1 knock-out compared with wild-type mice. With [Formula: see text] present, gradients for pHi (∼0.2 units magnitude) exist along the axis of VSMC migration in primary explants from wild-type but not NBCn1 knock-out mice. Knock-out or pharmacological inhibition of NBCn1 also reduces filopodia and lowers initial rates of VSMC migration after scratch-wound infliction. Interventions to reduce H(+)-buffer mobility (omission of [Formula: see text] or inhibition of carbonic anhydrases) re-establish axial pHi gradients, filopodia, and migration rates in explants from NBCn1 knock-out mice. The omission of [Formula: see text] also lowers global pHi and inhibits proliferation in primary explants. Under physiological conditions (i.e. with [Formula: see text] present), NBCn1-mediated [Formula: see text] uptake raises VSMC pHi and promotes filopodia, VSMC migration, and hypertrophic inward remodelling. We propose that axial pHi gradients enhance VSMC migration whereas global acidification inhibits VSMC proliferation and media hypertrophy after carotid artery ligation. These findings support a key role of acid-base transport, particularly via NBCn1, for development of occlusive artery disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  19. Solubility of NaNd(CO3)2.6H2O(c) in concentrated Na2CO3 and NaHCO3 solutions

    International Nuclear Information System (INIS)

    Rao, L.; Rai, D.; Felmy, A.R.; Fulton, R.W.; Novak, C.F.

    1996-01-01

    NaNd(CO 3 ) 2 x 6 H 2 O(c) was identified to be the final equilibrium solid phase in suspensions containing concentrated sodium carbonate (0.1 to 2.0 M) and sodium bicarbonate (0.1 to 1.0 M), with either NaNd(CO 3 ) 2 x 6 H 2 O(c) or Nd 2 (CO 3 ) 3 x xH 2 O(s) as initial solids. A thermodynamic model, based on Pitzer's specific into-interaction approach, was developed to interpret the solubility of NaNd(CO 3 ) 2 x 6 H 2 O(c) as functions of sodium carbonate and sodium bicarbonate concentrations. In this model, the solubility data of NaNd(CO 3 ) 2 x 6 H 2 O(c) were explained by assuming the formation of NdCO 3 + , Nd(CO 3 ) 2 - and Nd(CO 3 ) 3 3- species and invoking the specific ion interactions between Na + and Nd(CO 3 ) 3 3- . Ion interaction parameters for Na + -Nd(CO 3 ) 3 3- were developed to fit the solubility data. Based on the model calculations, Nd(CO 3 ) 3 3- was the predominant aqueous neodymium species in 0.1 to 2 M sodium carbonate and 0.1 to 1 M sodium bicarbonate solutions. The logarithm of the NaNd(CO 3 ) 2 x 6 H 2 O solubility product (NaNd(CO 3 ) 2 x 6 H 2 O(c)=Na + +Nd 3+ +2 CO 3 2- +6 H 2 O) was calculated to be -21.39. This model also provided satisfactory interpretation of the solubility data of the analogous Am(III) system in less concentrated carbonate and bicarbonate solutions. (orig.)

  20. Coupling between mass transfer and chemical reactions during the absorption of CO2 in a NaHCO3-Na2CO3 brine :experimental and theoretical study

    OpenAIRE

    Wylock, Christophe; Colinet, Pierre; Cartage, Thierry; Haut, Benoît

    2008-01-01

    This work deals with the study of the gas-liquid mass transfer, coupled with chemical reactions. The case of carbonic gas absorption in a brine of sodium carbonate and bicarbonate is investigated. It is performed in collaboration with Solvay SA. The aim of this work is to get a better understanding of this phenomenon. It would permit an optimization of the refined sodium bicarbonate production process. The basis of developed mathematical models is presented. The CO2 absorption is coupled with...

  1. Isolation, purification, and partial characterization of a membrane-bound Cl-/HCO3--activated ATPase complex from rat brain with sensitivity to GABAAergic ligands.

    Science.gov (United States)

    Menzikov, Sergey A

    2017-02-07

    This study describes the isolation and purification of a protein complex with [Formula: see text]-ATPase activity and sensitivity to GABA A ergic ligands from rat brain plasma membranes. The ATPase complex was enriched using size-exclusion, affinity, and ion-exchange chromatography. The fractions obtained at each purification step were subjected to SDS-polyacrylamide gel electrophoresis (SDS-PAGE), which revealed four subunits with molecular mass ∼48, 52, 56, and 59 kDa; these were retained at all stages of the purification process. Autoradiography revealed that the ∼52 and 56 kDa subunits could bind [ 3 H]muscimol. The [Formula: see text]-ATPase activity of this enriched protein complex was regulated by GABA A ergic ligands but was not sensitive to blockers of the NKCC or KCC cotransporters.

  2. Studi Ketebalan Elektroda Pada Produksi Gas HHO (Hidrogen Hidrogen Oksigen) Oleh Generator Hho Tipe Basah Dengan Katalis NaHCO3 (Natrium Bikarbonat)

    OpenAIRE

    Ihsan Sopandi; Yuli Hananto; Bayu Rudiyanto

    2015-01-01

    Abstrak. Salah satu energi alternatif yang efektif dikembangkan sekarang ini untuk mengganti bahan bakar minyak yaitu hidrogen. Untuk mendapatkan gas hidrogen dapat  dilakukan melalui proses elektrolisis air dengan memecahkan senyawa H2O menjadi gas HHO (Hidrogen Hidrogen Oksigen) dengan bantuan listrik arus searah (Direct Current) melalui media elektroda berupa plat stainless steel 304. Pada penelitian ini, akan diteliti hasil produksi gas HHO oleh generator HHO tipe basah dengan metode elek...

  3. Acid-base disturbances in nephrotic syndrome: analysis using the CO2/HCO3 method (traditional Boston model) and the physicochemical method (Stewart model).

    Science.gov (United States)

    Kasagi, Tomomichi; Imai, Hirokazu; Miura, Naoto; Suzuki, Keisuke; Yoshino, Masabumi; Nobata, Hironobu; Nagai, Takuhito; Banno, Shogo

    2017-10-01

    The Stewart model for analyzing acid-base disturbances emphasizes serum albumin levels, which are ignored in the traditional Boston model. We compared data derived using the Stewart model to those using the Boston model in patients with nephrotic syndrome. Twenty-nine patients with nephrotic syndrome and six patients without urinary protein or acid-base disturbances provided blood and urine samples for analysis that included routine biochemical and arterial blood gas tests, plasma renin activity, and aldosterone. The total concentration of non-volatile weak acids (A TOT ), apparent strong ion difference (SIDa), effective strong ion difference (SIDe), and strong ion gap (SIG) were calculated according to the formulas of Agrafiotis in the Stewart model. According to the Boston model, 25 of 29 patients (90%) had alkalemia. Eighteen patients had respiratory alkalosis, 11 had metabolic alkalosis, and 4 had both conditions. Only three patients had hyperreninemic hyperaldosteronism. The Stewart model demonstrated respiratory alkalosis based on decreased PaCO 2 , metabolic alkalosis based on decreased A TOT , and metabolic acidosis based on decreased SIDa. We could diagnose metabolic alkalosis or acidosis with a normal anion gap after comparing delta A TOT [(14.09 - measured A TOT ) or (11.77 - 2.64 × Alb (g/dL))] and delta SIDa [(42.7 - measured SIDa) or (42.7 - (Na + K - Cl)]). We could also identify metabolic acidosis with an increased anion gap using SIG > 7.0 (SIG = 0.9463 × corrected anion gap-8.1956). Patients with nephrotic syndrome had primary respiratory alkalosis, decreased A TOT due to hypoalbuminemia (power to metabolic alkalosis), and decreased levels of SIDa (power to metabolic acidosis). We could detect metabolic acidosis with an increased anion gap by calculating SIG. The Stewart model in combination with the Boston model facilitates the analysis of complex acid-base disturbances in nephrotic syndrome.

  4. Novel roles of the Na+/H+ exchanger NHE1 and the Na+,HCO3 - cotransporter NBCn1 in cell survival, proliferation and motility

    DEFF Research Database (Denmark)

    Thorup, Gitte Ehrenreich

    and cell motility. The molecular mechanisms contributing to altered pHi regulation in cancer cells are incomplete understood. Overexpression of ErbB2 is common in breast cancer and the expression of an N-terminally truncated, constitutively active ErbB2 receptor (ΔNErbB2) is associated with increased....... Pharmacological inhibition of NHE1 enhances cisdiamminedichloroplatinum (II) (cisplatin) induced cell death, especially in ΔNErbB2 expressing cells. In Paper III we show that upon cisplatin treatment, expression of ΔNErbB2 results in increased caspase-9 and -7 cleavage, which is further augmented by specific...... inhibition of NHE1. Moreover, NBCN1, yet not NHE1, is lost from the plasma membrane upon cisplatin treatment, and this may explain why inhibition of NHE1 sensitizes the cells to cisplatin-induced cell death. In Paper II we show that in MCF-7 breast cancer cells, the expression levels of NBCn1 and NHE1...

  5. Expression of Na+/HCO3- co-transporter proteins (NBCs) in rat and human skeletal muscle

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Kristensen, Michael; Juel, Carsten

    2004-01-01

    AIM: Sodium/bicarbonate co-transport (NBC) has been suggested to have a role in muscle pH regulation. We investigated the presence of NBC proteins in rat and human muscle samples and the fibre type distribution of the identified NBCs. METHODS AND RESULTS: Western blotting of muscle homogenates...... the T-tubules. The two NBCs localized in muscle have distinct fibre type distributions. CONCLUSIONS: Skeletal muscle possesses two variants of the sodium/bicarbonate co-transporter (NBC) isoforms, which have been called NBCe1 and NBCe2....... and sarcolemmal membranes (sarcolemmal giant vesicles) were used to screen for the presence of NBCs. Immunohistochemistry was used for the subcellular localization. The functional test revealed that approximately half of the pH recovery in sarcolemmal vesicles produced from rat muscle is mediated by bicarbonate...

  6. Some processes of energy saving and expenditure occurring during ethanol perfusion in the isolated liver of fed rats; a Nuclear Magnetic Resonance study.

    Directory of Open Access Journals (Sweden)

    Gin Henri

    2004-03-01

    Full Text Available Abstract Background In the isolated liver of fed rats, a 10 mM ethanol perfusion rapidly induced a rapid 25% decrease in the total ATP content, the new steady state resulting from both synthesis and consumption. The in situ rate of mitochondrial ATP synthesis without activation of the respiration was increased by 27%, implying an increased energy demand. An attempt to identify the ethanol-induced ATP-consuming pathways was performed using 31P and 13C Nuclear Magnetic Resonance. Results Ethanol (i transiently increased sn-glycerol-3-phosphate formation whereas glycogenolysis was continuously maintained; (ii decreased the glycolytic ATP supply and (iii diminished the intracellular pH in a dose-dependent manner in a slight extend. Although the cytosolic oxidation of ethanol largely generated H+ (and NADH, intracellular pHi was maintained by (i the large and passive excretion of cellular acetic acid arising from ethanol oxidation (evidenced by exogenous acetate administration, without energetic cost or (ii proton extrusion via the Na+-HCO3- symport (implying the indirect activation of the Na+-K+-ATPase pump and thus an energy use, demonstrated during the addition of their specific inhibitors SITS and ouabaïn, respectively. Conclusion Various cellular mechanisms diminish the cytosolic concentration of H+ and NADH produced by ethanol oxidation, such as (i the large but transient contribution of the dihydroxyacetone phosphate / sn-glycerol-3-phosphate shuttle between cytosol and mitochondria, mainly implicated in the redox state and (ii the major participation of acetic acid in passive proton extrusion out of the cell. These processes are not ATP-consuming and the latter is a cellular way to save some energy. Their starting in conjunction with the increase in mitochondrial ATP synthesis in ethanol-perfused whole liver was however insufficient to alleviate either the inhibition of glycolytic ATP synthesis and/or the implication of Na+-HCO3- symport and

  7. The yeast H+-ATPase Pma1 promotes Rag/Gtr-dependent TORC1 activation in response to H+-coupled nutrient uptake.

    Science.gov (United States)

    Saliba, Elie; Evangelinos, Minoas; Gournas, Christos; Corrillon, Florent; Georis, Isabelle; André, Bruno

    2018-03-23

    The yeast Target of Rapamycin Complex 1 (TORC1) plays a central role in controlling growth. How amino acids and other nutrients stimulate its activity via the Rag/Gtr GTPases remains poorly understood. We here report that the signal triggering Rag/Gtr-dependent TORC1 activation upon amino-acid uptake is the coupled H + influx catalyzed by amino-acid/H + symporters. H + -dependent uptake of other nutrients, ionophore-mediated H + diffusion, and inhibition of the vacuolar V-ATPase also activate TORC1. As the increase in cytosolic H + elicited by these processes stimulates the compensating H + -export activity of the plasma membrane H + -ATPase (Pma1), we have examined whether this major ATP-consuming enzyme might be involved in TORC1 control. We find that when the endogenous Pma1 is replaced with a plant H + -ATPase, H + influx or increase fails to activate TORC1. Our results show that H + influx coupled to nutrient uptake stimulates TORC1 activity and that Pma1 is a key actor in this mechanism. © 2018, Saliba et al.

  8. Chemical dependence - resources

    Science.gov (United States)

    Substance use - resources, Drug abuse - resources; Resources - chemical dependence ... are a good resource for information on drug dependence: National Council on Alcoholism and Drug Dependence -- ncadd. ...

  9. Regulating NETosis: Increasing pH Promotes NADPH Oxidase-Dependent NETosis

    Science.gov (United States)

    Khan, Meraj A.; Philip, Lijy M.; Cheung, Guillaume; Vadakepeedika, Shawn; Grasemann, Hartmut; Sweezey, Neil; Palaniyar, Nades

    2018-01-01

    Neutrophils migrating from the blood (pH 7.35–7.45) into the surrounding tissues encounter changes in extracellular pH (pHe) conditions. Upon activation of NADPH oxidase 2 (Nox), neutrophils generate large amounts of H+ ions reducing the intracellular pH (pHi). Nevertheless, how extracellular pH regulates neutrophil extracellular trap (NET) formation (NETosis) is not clearly established. We hypothesized that increasing pH increases Nox-mediated production of reactive oxygen species (ROS) and neutrophil protease activity, stimulating NETosis. Here, we found that raising pHe (ranging from 6.6 to 7.8; every 0.2 units) increased pHi of both activated and resting neutrophils within 10–20 min (Seminaphtharhodafluor dual fluorescence measurements). Since Nox activity generates H+ ions, pHi is lower in neutrophils that are activated compared to resting. We also found that higher pH stimulated Nox-dependent ROS production (R123 generation; flow cytometry, plate reader assay, and imaging) during spontaneous and phorbol myristate acetate-induced NETosis (Sytox Green assays, immunoconfocal microscopy, and quantifying NETs). In neutrophils that are activated and not resting, higher pH stimulated histone H4 cleavage (Western blots) and NETosis. Raising pH increased Escherichia coli lipopolysaccharide-, Pseudomonas aeruginosa (Gram-negative)-, and Staphylococcus aureus (Gram-positive)-induced NETosis. Thus, higher pHe promoted Nox-dependent ROS production, protease activity, and NETosis; lower pH has the opposite effect. These studies provided mechanistic steps of pHe-mediated regulation of Nox-dependent NETosis. Raising pH either by sodium bicarbonate or Tris base (clinically known as Tris hydroxymethyl aminomethane, tromethamine, or THAM) increases NETosis. Each Tris molecule can bind 3H+ ions, whereas each bicarbonate HCO3− ion binds 1H+ ion. Therefore, the amount of Tris solution required to cause the same increase in pH level is less than that of equimolar

  10. Regulating NETosis: Increasing pH Promotes NADPH Oxidase-Dependent NETosis

    Directory of Open Access Journals (Sweden)

    Meraj A. Khan

    2018-02-01

    Full Text Available Neutrophils migrating from the blood (pH 7.35–7.45 into the surrounding tissues encounter changes in extracellular pH (pHe conditions. Upon activation of NADPH oxidase 2 (Nox, neutrophils generate large amounts of H+ ions reducing the intracellular pH (pHi. Nevertheless, how extracellular pH regulates neutrophil extracellular trap (NET formation (NETosis is not clearly established. We hypothesized that increasing pH increases Nox-mediated production of reactive oxygen species (ROS and neutrophil protease activity, stimulating NETosis. Here, we found that raising pHe (ranging from 6.6 to 7.8; every 0.2 units increased pHi of both activated and resting neutrophils within 10–20 min (Seminaphtharhodafluor dual fluorescence measurements. Since Nox activity generates H+ ions, pHi is lower in neutrophils that are activated compared to resting. We also found that higher pH stimulated Nox-dependent ROS production (R123 generation; flow cytometry, plate reader assay, and imaging during spontaneous and phorbol myristate acetate-induced NETosis (Sytox Green assays, immunoconfocal microscopy, and quantifying NETs. In neutrophils that are activated and not resting, higher pH stimulated histone H4 cleavage (Western blots and NETosis. Raising pH increased Escherichia coli lipopolysaccharide-, Pseudomonas aeruginosa (Gram-negative-, and Staphylococcus aureus (Gram-positive-induced NETosis. Thus, higher pHe promoted Nox-dependent ROS production, protease activity, and NETosis; lower pH has the opposite effect. These studies provided mechanistic steps of pHe-mediated regulation of Nox-dependent NETosis. Raising pH either by sodium bicarbonate or Tris base (clinically known as Tris hydroxymethyl aminomethane, tromethamine, or THAM increases NETosis. Each Tris molecule can bind 3H+ ions, whereas each bicarbonate HCO3− ion binds 1H+ ion. Therefore, the amount of Tris solution required to cause the same increase in pH level is less than that of equimolar

  11. Propositional Logics of Dependence

    NARCIS (Netherlands)

    Yang, F.; Väänänen, J.

    2016-01-01

    In this paper, we study logics of dependence on the propositional level. We prove that several interesting propositional logics of dependence, including propositional dependence logic, propositional intuitionistic dependence logic as well as propositional inquisitive logic, are expressively complete

  12. Discovery of Paradigm Dependencies

    OpenAIRE

    Sun, Jizhou; Li, Jianzhong; Gao, Hong

    2017-01-01

    Missing and incorrect values often cause serious consequences. To deal with these data quality problems, a class of common employed tools are dependency rules, such as Functional Dependencies (FDs), Conditional Functional Dependencies (CFDs) and Edition Rules (ERs), etc. The stronger expressing ability a dependency has, data with the better quality can be obtained. To the best of our knowledge, all previous dependencies treat each attribute value as a non-splittable whole. Actually however, i...

  13. [Dependent patient and interpersonal dependency: psychotherapeutic strategies].

    Science.gov (United States)

    Versaevel, C

    2012-04-01

    This article is a review of psychotherapies for patients suffering from dependent personality and interpersonal dependency. We synthesized articles making reference to this question, notably those written by Bornstein, author who refers to the dependent personality. We highlighted the psychotherapies that have been the object of an evaluation. The research on the subject is sparse: only eight studies permitting assessment of psychotherapies in this indication in 2005. Besides these psychotherapies, we detailed other approaches which are used by practitioners in these indications. The therapy does not aim at autonomy "at all costs", but that the patient finds a dependence "adapted" to his/her environment. Before starting a therapy, an evaluation is useful to specify the type of dependence. First of all, is there a "pathological" dependence? Is the suffering of the patient secondary to his personality or not supportive enough? Does insight exist? What is the reaction of the patient if we suggest the hypothesis of a dependence on his/her part? Does he/she consider this idea or reject it? Finally, is the dependence primary or secondary? For that purpose, it is necessary to study the biography of the patient and the appearance of the comorbidity over time. The primary dependence is seen in childhood and precedes the other psychological disorders. The secondary dependence follows after the comorbidity and events of life that alter self-esteem (depression, for example). Various therapeutic strategies arise from various currents. The therapies of analytical inspiration recommend replaying the relationship of object and explicitly evoking the transfer. The behavioural and cognitive psychotherapies aim at making the patient identify the cognitions which underlie the dependence, then leading the patient to modify his/her cognition and to behave in a more autonomous way, using the theory of learning. The humanist therapies aim at a therapeutic relationship of acceptance and

  14. The molecular mechanism of ion-dependent gating in secondary transporters.

    Directory of Open Access Journals (Sweden)

    Chunfeng Zhao

    2013-10-01

    Full Text Available LeuT-like fold Na-dependent secondary active transporters form a large family of integral membrane proteins that transport various substrates against their concentration gradient across lipid membranes, using the free energy stored in the downhill concentration gradient of sodium ions. These transporters play an active role in synaptic transmission, the delivery of key nutrients, and the maintenance of osmotic pressure inside the cell. It is generally believed that binding of an ion and/or a substrate drives the conformational dynamics of the transporter. However, the exact mechanism for converting ion binding into useful work has yet to be established. Using a multi-dimensional path sampling (string-method followed by all-atom free energy simulations, we established the principal thermodynamic and kinetic components governing the ion-dependent conformational dynamics of a LeuT-like fold transporter, the sodium/benzyl-hydantoin symporter Mhp1, for an entire conformational cycle. We found that inward-facing and outward-facing states of Mhp1 display nearly the same free energies with an ion absent from the Na2 site conserved across the LeuT-like fold transporters. The barrier separating an apo-state from inward-facing or outward-facing states of the transporter is very low, suggesting stochastic gating in the absence of ion/substrate bound. In contrast, the binding of a Na2 ion shifts the free energy stabilizing the outward-facing state and promoting substrate binding. Our results indicate that ion binding to the Na2 site may also play a key role in the intracellular thin gate dynamics modulation by altering its interactions with the transmembrane helix 5 (TM5. The Potential of Mean Force (PMF computations for a substrate entrance displays two energy minima that correspond to the locations of the main binding site S1 and proposed allosteric S2 binding site. However, it was found that substrate's binds to the site S1 ∼5 kcal/mol more favorable

  15. Zn2+ modulation of neurotransmitter transporters

    DEFF Research Database (Denmark)

    Nørgaard-Nielsen, K.; Gether, U.

    2006-01-01

    of neurotransmitter transporters have been identified based on sequence homology: (1) the neurotransmitter sodium symporter family (NSS), which includes the Na+/C1(-)-dependent transporters for dopamine, norepinephrine, and serotonin; and (2) the dicarboxylate/amino acid cation symporter family (DAACS), which...

  16. Constraining Path-Dependent Processes During Basalt-CO2 Interactions with Observations From Flow-Through and Batch Experiments

    Science.gov (United States)

    Thomas, D.; Garing, C.; Zahasky, C.; Harrison, A. L.; Bird, D. K.; Benson, S. M.; Oelkers, E. H.; Maher, K.

    2017-12-01

    Predicting the timing and magnitude of CO2 storage in basaltic rocks relies partly on quantifying the dependence of reactivity on flow path and mineral distribution. Flow-through experiments that use intact cores are advantageous because the spatial heterogeneity of pore space and reactive phases is preserved. Combining aqueous geochemical analyses and petrologic characterization with non-destructive imaging techniques (e.g. micro-computed tomography) constrains the relationship between irreversible reactions, pore connectivity and accessible surface area. Our work enhances these capabilities by dynamically imaging flow through vesicular basalts with Positron Emission Tomography (PET) scanning. PET highlights the path a fluid takes by detecting photons produced during radioactive decay of an injected radiotracer (FDG). We have performed single-phase, CO2-saturated flow-through experiments with basaltic core from Iceland at CO2 sequestration conditions (50 °C; 76-90 bar Ptot). Constant flow rate and continuous pressure measurements at the inlet and outlet of the core constrain permeability. We monitor geochemical evolution through cation and anion analysis of outlet fluid sampled periodically. Before and after reaction, we perform PET scans and characterize the core using micro-CT. The PET scans indicate a discrete, localized flow path that appears to be a micro-crack connecting vesicles, suggesting that vesicle-lining minerals are immediately accessible and important reactants. Rapid increases in aqueous cation concentration, pH and HCO3- indicate that the rock reacts nearly immediately after CO2 injection. After 24 hours the solute release decreases, which may reflect a transition to reaction with phases with slower kinetic dissolution rates (e.g. zeolites and glasses to feldspar), a decrease in available reactive surface area or precipitation. We have performed batch experiments using crushed material of the same rock to elucidate the effect of flow path

  17. Slovak Dependency Treebank in Universal Dependencies

    Directory of Open Access Journals (Sweden)

    Zeman Daniel

    2017-12-01

    Full Text Available We describe a conversion of the syntactically annotated part of the Slovak National Corpus into the annotation scheme known as Universal Dependencies. Only a small subset of the data has been converted so far; yet it is the first Slovak treebank that is publicly available for research. We list a number of research projects in which the dataset has been used so far, including the first parsing results.

  18. Caffeine dependence in teenagers.

    Science.gov (United States)

    Bernstein, Gail A; Carroll, Marilyn E; Thuras, Paul D; Cosgrove, Kelly P; Roth, Megan E

    2002-03-01

    This study identifies and characterizes symptoms of caffeine dependence in adolescents. Thirty-six adolescents who consumed caffeine daily and had some features of caffeine dependence on telephone screen were scheduled for outpatient evaluation. Evaluation included the Diagnostic Interview Schedule for Children-IV-Youth Version (DISC-IV) and modified DISC-IV questions that assessed caffeine dependence based on DSM-IV substance dependence criteria. Of 36 subjects, 41.7% (n=15) reported tolerance to caffeine, 77.8% (n=28) described withdrawal symptoms after cessation or reduction of caffeine intake, 38.9% (n=14) reported desire or unsuccessful attempts to control use, and 16.7% (n=6) endorsed use despite knowledge of physical or psychological problems associated with caffeine. There was no significant difference in the amount of caffeine consumed daily by caffeine dependent versus non-dependent teenagers. These findings are important due to the vast number of adolescents who drink caffeinated beverages.

  19. Ecstasy (MDMA) dependence.

    Science.gov (United States)

    Jansen, K L

    1999-01-07

    Methylenedioxymethamphetamine (MDMA) is generally described as non-addictive. However, this report describes three cases in which criteria for dependence were met. A wider understanding that MDMA can be addictive in rare cases is important as very heavy use may cause lasting neuronal changes. This risk could be reduced with effective identification and treatment of dependent persons. In one case dependence was linked with self-medication of post-traumatic stress disorder (PTSD).

  20. Systems dependability assessment

    CERN Document Server

    Aubry, Jean-François

    2015-01-01

    Presents recent developments of probabilistic assessment of systems dependability based on stochastic models, including graph theory, finite state automaton and language theory, for both dynamic and hybrid contexts.

  1. Adam Smith and dependency.

    Science.gov (United States)

    Ozler, Sule

    2012-06-01

    The focus of this paper is the works and life of Adam Smith, who is widely recognized as the father and founder of contemporary economics. Latent content analysis is applied to his seminal text in economics, An Inquiry into the Nature and Causes of the Wealth of Nations (1776). The results reveal that Smith considers dependence on others a problem and sees the solution to this problem in impersonalized interdependence. In addition, his views on social dependency and personal dependency, reflected in his Lectures on Jurisprudence (1963) and The Theory of Moral Sentiments (1759), are analyzed. This analysis suggests a central tension between dependence and independence in Smith's writings. The personal dependency patterns he exhibited in his life, which also suggest a tension between dependence and independence, are identified through a reading of his biographies. Based on insights from psychoanalytic literature, this paper proposes that developing the ideas in the Wealth of Nations was part of Smith's creative solution to this tension. In particular, his solution to one individual's dependence on another was through a system of impersonalized interdependence. In other words, Smith defended against his personal dependence through his economic theorizing.

  2. Improving Loop Dependence Analysis

    DEFF Research Database (Denmark)

    Jensen, Nicklas Bo; Karlsson, Sven

    2017-01-01

    Programmers can no longer depend on new processors to have significantly improved single-thread performance. Instead, gains have to come from other sources such as the compiler and its optimization passes. Advanced passes make use of information on the dependencies related to loops. We improve th...

  3. Gradle dependency management

    CERN Document Server

    Ikkink, Hubert Klein

    2015-01-01

    If you work on Java projects, use Gradle as a build automation tool, and you use dependencies in your project, this is the book for you. Additionally, if you want to deploy your project artifacts as dependencies for other developers using Gradle, you've found the right book.

  4. Grelling on dependence

    NARCIS (Netherlands)

    Väänänen, J.; Abramsky, S.; Kontinen, J.; Väänänen, J.; Vollmer, H.

    2016-01-01

    Kurt Grelling wrote a paper in 1939 presenting various concepts of dependence. The paper remained unpublished, but deserves to be read today. Many of the ideas of the paper have been subsequently reinvented but one concept, which we call G-dependence, is still genuinely new, and that is the main

  5. Decisions Concerning Directional Dependence

    Science.gov (United States)

    von Eye, Alexander; DeShon, Richard P.

    2012-01-01

    In this rejoinder, von Eye and DeShon discuss the decision strategies proposed in their original article ("Directional Dependence in Developmental Research," this issue), as well as the ones proposed by the authors of the commentary (Pornprasertmanit and Little, "Determining Directional Dependency in Causal Associations," this issue). In addition,…

  6. The Politics of Dependence

    DEFF Research Database (Denmark)

    Cockburn, Patrick Joseph

    The central claim of this book is that thinking about ‘dependence’ should be at the core of political theory principally because it helps us to think about issues of economic justice. Unlike political theories that either condemn or celebrate dependence, the book argues that dependence...... is an inescapable fact of social life, neither good nor bad in itself. The real political issues are about how we as a society organise and judge various forms of dependence. And this is, in fact, what much political debate is about if we dig beneath the surface. On the one hand, we disagree about how we should...... organise vulnerability; on the other hand, we disagree about who we should condemn as parasitical. Vulnerability and parasitism are thus key concepts for understanding political debate about forms of dependence. Showing the tension between these two sides to the problem of economic dependence...

  7. Flow dependent water quality impacts of historic coal and oil shale mining in the Almond River catchment, Scotland

    International Nuclear Information System (INIS)

    Haunch, Simon; MacDonald, Alan M.; Brown, Neil; McDermott, Christopher I.

    2013-01-01

    . Interpretation of major ion chemistry data for 2005–2006 indicates significant increases in Ca 2+ , Mg 2+ and HCO 3 - in coal mined areas probably as a result of the buffering of proton acidity in mine waters; in the oil shale areas Na − and Cl − become increasing dominant possibly associated with increased urbanisation and saline pore water discharge from unprocessed oil shale waste. The study demonstrates the importance of considering the cumulative impact of point and diffuse contamination sourced from numerous small coal and oil shale mine sites on surface water quality

  8. Time-dependent embedding

    OpenAIRE

    Inglesfield, J. E.

    2007-01-01

    A method of solving the time-dependent Schr\\"odinger equation is presented, in which a finite region of space is treated explicitly, with the boundary conditions for matching the wave-functions on to the rest of the system replaced by an embedding term added on to the Hamiltonian. This time-dependent embedding term is derived from the Fourier transform of the energy-dependent embedding potential, which embeds the time-independent Schr\\"odinger equation. Results are presented for a one-dimensi...

  9. Security of Dependable Systems

    DEFF Research Database (Denmark)

    Ahmed, Naveed; Jensen, Christian D.

    2011-01-01

    Security and dependability are crucial for designing trustworthy systems. The approach “security as an add-on” is not satisfactory, yet the integration of security in the development process is still an open problem. Especially, a common framework for specifying dependability and security is very...... much needed. There are many pressing challenges however; here, we address some of them. Firstly, security for dependable systems is a broad concept and traditional view of security, e.g., in terms of confidentiality, integrity and availability, does not suffice. Secondly, a clear definition of security...... in the dependability context is not agreed upon. Thirdly, security attacks cannot be modeled as a stochastic process, because the adversary’s strategy is often carefully planned. In this chapter, we explore these challenges and provide some directions toward their solutions....

  10. Apache Maven dependency management

    CERN Document Server

    Lalou, Jonathan

    2013-01-01

    An easy-to-follow, tutorial-based guide with chapters progressing from basic to advanced dependency management.If you are working with Java or Java EE projects and you want to take advantage of Maven dependency management, then this book is ideal for you. This book is also particularly useful if you are a developer or an architect. You should be well versed with Maven and its basic functionalities if you wish to get the most out of this book.

  11. Time Dependent Quantum Mechanics

    OpenAIRE

    Morrison, Peter G.

    2012-01-01

    We present a systematic method for dealing with time dependent quantum dynamics, based on the quantum brachistochrone and matrix mechanics. We derive the explicit time dependence of the Hamiltonian operator for a number of constrained finite systems from this formalism. Once this has been achieved we go on to calculate the wavevector as a function of time, in order to demonstrate the use of matrix methods with respect to several concrete examples. Interesting results are derived for elliptic ...

  12. Size-dependent thermoelasticity

    Directory of Open Access Journals (Sweden)

    Ali R. Hadjesfandiari

    Full Text Available In this paper a consistent theory is developed for size-dependent thermoelasticity in heterogeneous anisotropic solids. This theory shows that the temperature change can create not only thermal strains, but also thermal mean curvatures in the solids. This formulation is based on the consistent size-dependent continuum mechanics in which the couple-stress tensor is skew-symmetric. Here by including scale-dependent measures in the energy and entropy equations, the general expressions for force- and couple-stresses, as well as entropy density, are obtained. Next, for the linear material the constitutive relations and governing coupled size-dependent thermoelasticity equations are developed. For linear material, one can see that the thermal properties are characterized by the classical symmetric thermal expansion tensor and the new size-dependent skew-symmetric thermal flexion tensor. Thus, for the most general anisotropic case, there are nine independent thermoelastic constants. Interestingly, for isotropic and cubic materials the thermal flexion tensor vanishes, which shows there is no thermal mean curvature

  13. Path-dependent functions

    International Nuclear Information System (INIS)

    Khrapko, R.I.

    1985-01-01

    A uniform description of various path-dependent functions is presented with the help of expansion of the type of the Taylor series. So called ''path-integrals'' and ''path-tensor'' are introduced which are systems of many-component quantities whose values are defined for arbitrary paths in coordinated region of space in such a way that they contain a complete information on the path. These constructions are considered as elementary path-dependent functions and are used instead of power monomials in the usual Taylor series. Coefficients of such an expansion are interpreted as partial derivatives dependent on the order of the differentiations or else as nonstandard cavariant derivatives called two-point derivatives. Some examples of pathdependent functions are presented.Space curvature tensor is considered whose geometrica properties are determined by the (non-transitive) translator of parallel transport of a general type. Covariant operation leading to the ''extension'' of tensor fiels is pointed out

  14. Anticonvulsants for cocaine dependence.

    Science.gov (United States)

    Minozzi, Silvia; Cinquini, Michela; Amato, Laura; Davoli, Marina; Farrell, Michael F; Pani, Pier Paolo; Vecchi, Simona

    2015-04-17

    Cocaine dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence, none is currently available for cocaine dependence, despite two decades of clinical trials primarily involving antidepressant, anticonvulsivant and dopaminergic medications. Extensive consideration has been given to optimal pharmacological approaches to the treatment of individuals with cocaine dependence, and both dopamine antagonists and agonists have been considered. Anticonvulsants have been candidates for use in the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction. To evaluate the efficacy and safety of anticonvulsants for individuals with cocaine dependence. We searched the Cochrane Drugs and Alcohol Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1966 to June 2014), EMBASE (1988 to June 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2014), Web of Science (1991 to June 2014) and the reference lists of eligible articles. All randomised controlled trials and controlled clinical trials that focus on the use of anticonvulsant medications to treat individuals with cocaine dependence. We used the standard methodological procedures expected by The Cochrane Collaboration. We included a total of 20 studies with 2068 participants. We studied the anticonvulsant drugs carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. Only one study had one arm by which the anticonvulsant was compared with the antidepressant desipramine. Upon comparison of anticonvulsant versus placebo, we found no significant differences for any of the efficacy and safety measures. Dropouts: risk ratio (RR) 0.95, 95

  15. The Reproducibility of 4-km Time Trial (TT) Performance Following Individualised Sodium Bicarbonate Supplementation: a Randomised Controlled Trial in Trained Cyclists.

    Science.gov (United States)

    Gough, Lewis Anthony; Deb, Sanjoy Kumar; Sparks, Andy; McNaughton, Lars Robert

    2017-09-21

    Individual time to peak blood bicarbonate (HCO 3 - ) has demonstrated good to excellent reproducibility following ingestion of both 0.2 g kg -1 body mass (BM) and 0.3 g kg -1 BM sodium bicarbonate (NaHCO 3 ), but the consistency of the time trial (TT) performance response using such an individualised NaHCO 3 ingestion strategy remains unknown. This study therefore evaluated the reproducibility of 4-km TT performance following NaHCO 3 ingestion individualised to time to peak blood bicarbonate. Eleven trained male cyclists completed five randomised treatments with prior ingestion of 0.2 g kg -1 (SBC2) or 0.3 g kg -1 BM (SBC3) NaHCO 3 , on two separate occasions each, or a control trial entailing no supplementation. Participants completed a 4-km cycling TT on a Velotron ergometer where time to complete, power and speed were measured, whilst acid-base blood parameters were also recorded (pH and blood bicarbonate concentration HCO 3 - ) and lactate [La - ]. Alkalosis was achieved prior to exercise in both SBC2 and SBC3, as pH and HCO 3 - were greater compared to baseline (p  0.05). The reproducibility of the mean absolute change from baseline to peak in HCO 3 - was good in SBC2 (r = 0.68) and excellent in SBC3 (r = 0.78). The performance responses following both SBC2 and SBC3 displayed excellent reproducibility (r range = 0.97 to 0.99). Results demonstrate excellent reproducibility of exercise performance following individualised NaHCO 3 ingestion, which is due to the high reproducibility of blood acid-base variables with repeat administration of NaHCO 3 . Using a time to peak HCO 3 - strategy seems to cause no dose-dependent effects on performance for exercise of this duration and intensity; therefore, athletes may consider smaller doses of NaHCO 3 to mitigate gastrointestinal (GI) discomfort.

  16. State Dependence in Unemployment

    DEFF Research Database (Denmark)

    Ahmad, Nisar

    2014-01-01

    This study examines the extent state dependence among unemployed immigrants in a dynamic discrete choice framework. Three alternative methodologies are employed to control for the problem of the initial condition. The empirical findings show that there is a considerable correlation between the un...

  17. Pressure dependence of conductivity

    International Nuclear Information System (INIS)

    Bracewell, B.L.; Hochheimer, H.D.

    1993-01-01

    The overall objectives of this work were to attempt the following: (1) Measure the pressure dependence of the electrical conductivity of several quasi-one-dimensional, charge-density-wave solids, including measurements along various crystal directions. (2) Measure photocurrents in selected MX solids at ambient and elevated pressures. (3) Measure the resonance Raman spectra for selected MX solids as a function of pressure

  18. On Stochastic Dependence

    Science.gov (United States)

    Meyer, Joerg M.

    2018-01-01

    The contrary of stochastic independence splits up into two cases: pairs of events being favourable or being unfavourable. Examples show that both notions have quite unexpected properties, some of them being opposite to intuition. For example, transitivity does not hold. Stochastic dependence is also useful to explain cases of Simpson's paradox.

  19. Empirically sampling Universal Dependencies

    DEFF Research Database (Denmark)

    Schluter, Natalie; Agic, Zeljko

    2017-01-01

    Universal Dependencies incur a high cost in computation for unbiased system development. We propose a 100% empirically chosen small subset of UD languages for efficient parsing system development. The technique used is based on measurements of model capacity globally. We show that the diversity o...

  20. Reference-Dependent Sympathy

    Science.gov (United States)

    Small, Deborah A.

    2010-01-01

    Natural disasters and other traumatic events often draw a greater charitable response than do ongoing misfortunes, even those that may cause even more widespread misery, such as famine or malaria. Why is the response disproportionate to need? The notion of reference dependence critical to Prospect Theory (Kahneman & Tversky, 1979) maintains that…

  1. Temperature dependent anomalous statistics

    International Nuclear Information System (INIS)

    Das, A.; Panda, S.

    1991-07-01

    We show that the anomalous statistics which arises in 2 + 1 dimensional Chern-Simons gauge theories can become temperature dependent in the most natural way. We analyze and show that a statistic's changing phase transition can happen in these theories only as T → ∞. (author). 14 refs

  2. Why Density Dependent Propulsion?

    Science.gov (United States)

    Robertson, Glen A.

    2011-01-01

    In 2004 Khoury and Weltman produced a density dependent cosmology theory they call the Chameleon, as at its nature, it is hidden within known physics. The Chameleon theory has implications to dark matter/energy with universe acceleration properties, which implies a new force mechanism with ties to the far and local density environment. In this paper, the Chameleon Density Model is discussed in terms of propulsion toward new propellant-less engineering methods.

  3. Time dependent accessibility

    OpenAIRE

    Kaza, Nikhil

    2015-01-01

    Many place based accessibility studies ignore the time component. Relying on theoretical frameworks that treat distance between two fixed points as constant, these methods ignore the diurnal and seasonal changes in accessibility. Network distances between two nodes are dependent on the network structure and weight distribution on the edges. These weights can change quite frequently and the network structure itself is subject to modification because of availability and unavailability of links ...

  4. Scale-Dependent Grasp

    OpenAIRE

    Kaneko, Makoto; Shirai, Tatsuya; Tsuji, Toshio

    2000-01-01

    This paper discusses the scale-dependent grasp.Suppose that a human approaches an object initially placed on atable and finally achieves an enveloping grasp. Under such initialand final conditions, he (or she) unconsciously changes the graspstrategy according to the size of objects, even though they havesimilar geometry. We call the grasp planning the scale-dependentgrasp. We find that grasp patterns are also changed according tothe surface friction and the geometry of cross section in additi...

  5. MEASURING PATH DEPENDENCY

    Directory of Open Access Journals (Sweden)

    Peter Juhasz

    2017-03-01

    Full Text Available While risk management gained popularity during the last decades even some of the basic risk types are still far out of focus. One of these is path dependency that refers to the uncertainty of how we reach a certain level of total performance over time. While decision makers are careful in accessing how their position will look like the end of certain periods, little attention is given how they will get there through the period. The uncertainty of how a process will develop across a shorter period of time is often “eliminated” by simply choosing a longer planning time interval, what makes path dependency is one of the most often overlooked business risk types. After reviewing the origin of the problem we propose and compare seven risk measures to access path. Traditional risk measures like standard deviation of sub period cash flows fail to capture this risk type. We conclude that in most cases considering the distribution of the expected cash flow effect caused by the path dependency may offer the best method, but we may need to use several measures at the same time to include all the optimisation limits of the given firm

  6. From PSAs to dependability

    International Nuclear Information System (INIS)

    Desmas, T.; Lagrange, V.

    1996-01-01

    Dependability is all the concepts (Reliability, Availability, Maintainability, and Safety) which are used to characterize the capabilities of a product to operate, to be repaired, and to not cause damage to objects or persons. PSAs (Probabilistic Safety Assessments) are a particular means of assessing the level of safety of hazardous installations. The purpose of this communication is to show that although it is still an emerging concept within EDF projects, the introduction of methods for taking account of dependability in design can be very useful at improving the safety of plants by, for example, establishing the link between operating feedback on one hand, and maintenance and operating policy on the other. Finally, we will extend our thinking on the insertion of dependability (and PSA) into design work to consideration of human factors in these projects. All too often kept apart, the technical and human aspects of design projects do have common characteristics: participation in safety and ease of operational of power plants, need for sufficiently early insertion in order to obtain pertinent result, etc. 8 figs

  7. From PSAs to dependability

    Energy Technology Data Exchange (ETDEWEB)

    Desmas, T; Lagrange, V

    1997-12-31

    Dependability is all the concepts (Reliability, Availability, Maintainability, and Safety) which are used to characterize the capabilities of a product to operate, to be repaired, and to not cause damage to objects or persons. PSAs (Probabilistic Safety Assessments) are a particular means of assessing the level of safety of hazardous installations. The purpose of this communication is to show that although it is still an emerging concept within EDF projects, the introduction of methods for taking account of dependability in design can be very useful at improving the safety of plants by, for example, establishing the link between operating feedback on one hand, and maintenance and operating policy on the other. Finally, we will extend our thinking on the insertion of dependability (and PSA) into design work to consideration of human factors in these projects. All too often kept apart, the technical and human aspects of design projects do have common characteristics: participation in safety and ease of operational of power plants, need for sufficiently early insertion in order to obtain pertinent result, etc. 8 figs.

  8. Multivariate pattern dependence.

    Directory of Open Access Journals (Sweden)

    Stefano Anzellotti

    2017-11-01

    Full Text Available When we perform a cognitive task, multiple brain regions are engaged. Understanding how these regions interact is a fundamental step to uncover the neural bases of behavior. Most research on the interactions between brain regions has focused on the univariate responses in the regions. However, fine grained patterns of response encode important information, as shown by multivariate pattern analysis. In the present article, we introduce and apply multivariate pattern dependence (MVPD: a technique to study the statistical dependence between brain regions in humans in terms of the multivariate relations between their patterns of responses. MVPD characterizes the responses in each brain region as trajectories in region-specific multidimensional spaces, and models the multivariate relationship between these trajectories. We applied MVPD to the posterior superior temporal sulcus (pSTS and to the fusiform face area (FFA, using a searchlight approach to reveal interactions between these seed regions and the rest of the brain. Across two different experiments, MVPD identified significant statistical dependence not detected by standard functional connectivity. Additionally, MVPD outperformed univariate connectivity in its ability to explain independent variance in the responses of individual voxels. In the end, MVPD uncovered different connectivity profiles associated with different representational subspaces of FFA: the first principal component of FFA shows differential connectivity with occipital and parietal regions implicated in the processing of low-level properties of faces, while the second and third components show differential connectivity with anterior temporal regions implicated in the processing of invariant representations of face identity.

  9. pH sensing via bicarbonate-regulated ‘soluble’ adenylyl cyclase (sAC

    Directory of Open Access Journals (Sweden)

    Nawreen eRahman

    2013-11-01

    Full Text Available Soluble adenylyl cyclase (sAC is a source of the second messenger cyclic adenosine 3',5' monophosphate (cAMP. sAC is directly regulated by bicarbonate (HCO3- ions. In living cells, HCO3- ions are in nearly instantaneous equilibrium with carbon dioxide (CO2 and pH due to the ubiquitous presence of carbonic anhydrases. Numerous biological processes are regulated by CO2, HCO3-, and/or pH, and in a number of these, sAC has been shown to function as a physiological CO2/HCO3/pH sensor. In this review, we detail the known pH sensing functions of sAC, and we discuss two highly-studied, pH-dependent pathways in which sAC might play a role.

  10. Path dependence and creation

    DEFF Research Database (Denmark)

    Garud, Raghu; Karnøe, Peter

    This edited volume stems from a conference held in Copenhagen that the authors ran in August of 1997. The authors, aware of the recent work in evolutionary theory and the science of chaos and complexity, challenge the sometimes deterministic flavour of this work. They are interested in uncovering...... the place of agency in these theories that take history so seriously. In the end, they are as interested in path creation and destruction as they are in path dependence. This book is compiled of both theoretical and empirical writing. It shows relatively well-known industries such as the automobile...

  11. Mucociliary transport in porcine trachea: differential effects of inhibiting chloride and bicarbonate secretion.

    Science.gov (United States)

    Cooper, Jeffrey L; Quinton, Paul M; Ballard, Stephen T

    2013-02-01

    This study was designed to assess the relative importance of Cl(-) and HCO(3)(-) secretion to mucociliary transport rate (MCT) in ex vivo porcine tracheas. MCT was measured in one group of tissues that was exposed to adventitial HCO(3)(-)-free solution while a parallel group was exposed to adventitial HCO(3)(-)-replete solution. After measurement of baseline MCT rates, acetylcholine (ACh) was added to stimulate submucosal gland mucous liquid secretion, and MCT rates were again measured. Before ACh addition, the mean MCT was higher in the HCO(3)(-)-free group (4.2 ± 0.9 mm/min) than in the HCO(3)(-)-replete group (2.3 ± 0.3 mm/min), but this difference was not statistically significant. ACh addition significantly increased MCT in both groups, but ACh-stimulated MCT was significantly lower in the HCO(3)(-)-free group (11.0 ± 1.5 mm/min) than in the HCO(3)(-)-replete group (17.0 ± 2.0 mm/min). A second series of experiments examined the effect on MCT of blocking Cl(-) secretion with 100 μM bumetanide. Before adding ACh, MCT in the bumetanide-treated group (1.0 ± 0.2 mm/min) was significantly lower than in the control group (3.8 ± 1.1 mm/min). ACh addition significantly increased MCT in both groups, but there was no significant difference between the bumetanide-treated group (21.4 ± 1.7 mm/min) and control group (19.5 ± 3.4 mm/min). These results indicate that ACh-stimulated MCT has greater dependence on HCO(3)(-) secretion, whereas the basal MCT rate has greater dependence on Cl(-) secretion.

  12. Plasmalemmal V-H+-ATPases regulate intracellular pH in human lung microvascular endothelial cells

    International Nuclear Information System (INIS)

    Rojas, Jose D.; Sennoune, Souad R.; Maiti, Debasish; Martinez, Gloria M.; Bakunts, Karina; Wesson, Donald E.; Martinez-Zaguilan, Raul

    2004-01-01

    The lung endothelium layer is exposed to continuous CO 2 transit which exposes the endothelium to a substantial acid load that could be detrimental to cell function. The Na + /H + exchanger and HCO 3 - -dependent H + -transporting mechanisms regulate intracellular pH (pH cyt ) in most cells. Cells that cope with high acid loads might require additional primary energy-dependent mechanisms. V-H + -ATPases localized at the plasma membranes (pmV-ATPases) have emerged as a novel pH regulatory system. We hypothesized that human lung microvascular endothelial (HLMVE) cells use pmV-ATPases, in addition to Na + /H + exchanger and HCO 3 - -based H + -transporting mechanisms, to maintain pH cyt homeostasis. Immunocytochemical studies revealed V-H + -ATPase at the plasma membrane, in addition to the predicted distribution in vacuolar compartments. Acid-loaded HLMVE cells exhibited proton fluxes in the absence of Na + and HCO 3 - that were similar to those observed in the presence of either Na + , or Na + and HCO 3 - . The Na + - and HCO 3 - -independent pH cyt recovery was inhibited by bafilomycin A 1 , a V-H + -ATPase inhibitor. These studies show a Na + - and HCO 3 - -independent pH cyt regulatory mechanism in HLMVE cells that is mediated by pmV-ATPases

  13. Dependent seniors garment design

    Science.gov (United States)

    Caldas, A. L.; Carvalho, M. A.; Lopes, H. P.

    2017-10-01

    This paper is part of a PhD research in Textile Engineering at University of Minho and aims to establish an ergonomic pattern design methodology to be used in the construction of garments for elderly women, aged 65 and over, dependent of care. The research was developed with a close contact with four institutions involved in supporting this aged population, located in the cities of Guimarães (Portugal) and Teresina (Brazil). These clothes should be adequate to their anthropometrics and their special needs, in accordance with important functional factors for the dependency of their caregiver, such as: care for the caregiver and comfort for the user. Questions regarding the functional properties of the materials, the pattern design process, trimmings and the assembling process of the garments are specially considered in the desired comfort levels, in order to provide an adequate handling by facilitating the dressing and undressing tasks, but also to assure the user the needed comfort in all its variables.

  14. Oxygen Dependent Biocatalytic Processes

    DEFF Research Database (Denmark)

    Pedersen, Asbjørn Toftgaard

    Enzyme catalysts have the potential to improve both the process economics and the environ-mental profile of many oxidation reactions especially in the fine- and specialty-chemical industry, due to their exquisite ability to perform stereo-, regio- and chemo-selective oxida-tions at ambient...... to aldehydes and ketones, oxyfunctionalization of C-H bonds, and epoxidation of C-C double bonds. Although oxygen dependent biocatalysis offers many possibilities, there are numerous chal-lenges to be overcome before an enzyme can be implemented in an industrial process. These challenges requires the combined...... far below their potential maximum catalytic rate at industrially relevant oxygen concentrations. Detailed knowledge of the en-zyme kinetics are therefore required in order to determine the best operating conditions and design oxygen supply to minimize processing costs. This is enabled...

  15. Time dependent drift Hamiltonian

    International Nuclear Information System (INIS)

    Boozer, A.H.

    1982-04-01

    The motion of individual charged particles in a given magnetic and an electric fields is discussed. An idea of a guiding center distribution function f is introduced. The guiding center distribution function is connected to the asymptotic Hamiltonian through the drift kinetic equation. The general non-stochastic magnetic field can be written in a contravariant and a covariant forms. The drift Hamiltonian is proposed, and the canonical gyroradius is presented. The proposed drift Hamiltonian agrees with Alfven's drift velocity to lowest non-vanishing order in the gyroradius. The relation between the exact, time dependent equations of motion and the guiding center equation is clarified by a Lagrangian analysis. The deduced Lagrangian represents the drift motion. (Kato, T.)

  16. Energy India 'dependence

    International Nuclear Information System (INIS)

    Cygler, C.

    2007-01-01

    India has an economic growth between 8 to 10 % by year. To become a great country of the twenty first century and to stop poverty it is necessary to keep this growth but the growth of India is dependant of its ability to supply electric power necessary to increase the industrial production. The country has to multiply by four its energy production. The electric production comes from thermal power plants for 65%, 26% from hydroelectric power plants, 6% from renewable energy sources and 3% from nuclear energy. Between solar energy ( India has three hundred solar days by years) and nuclear energy using thorium that can be increased India has to choose an energy policy to answer its energy demand and independence need. (N.C.)

  17. Density dependent effective interactions

    International Nuclear Information System (INIS)

    Dortmans, P.J.; Amos, K.

    1994-01-01

    An effective nucleon-nucleon interaction is defined by an optimal fit to select on-and half-off-of-the-energy shell t-and g-matrices determined by solutions of the Lippmann-Schwinger and Brueckner-Bethe-Goldstone equations with the Paris nucleon-nucleon interaction as input. As such, it is seen to better reproduce the interaction on which it is based than other commonly used density dependent effective interactions. The new (medium modified) effective interaction when folded with appropriate density matrices, has been used to define proton- 12 C and proton- 16 O optical potentials. With them elastic scattering data are well fit and the medium effects identifiable. 23 refs., 8 figs

  18. Chemical Dependence and Personality

    Directory of Open Access Journals (Sweden)

    Carlos Henrique Sancineto da Silva Nunes

    2009-01-01

    Full Text Available This study investigated the relationships between chemical dependency and personalitystructure in a Brazilian sample. Participants were college students (n=35 and patients of a drug recovery center (n= 48. Two personality scales based on the Big-5 Model were used to measure Extraversion and Agreeableness. A semi-structured interview was used to identify events in the patients' life histories that might support specific classifications. Participants' scores were also compared to Brazilian normative samples. The results showed significant differences between clinical and non-clinical groups in Agreeableness, but not in Extraversion. Logistic regression analyses were conducted using scales and interview aspects for predicting group membership. The model showed 92.1% general predictive power. Results pointed to the advantage of using both interview and objective techniques to assess individuals with antisocial personality symptoms.

  19. Anticonvulsants for alcohol dependence.

    Science.gov (United States)

    Pani, Pier Paolo; Trogu, Emanuela; Pacini, Matteo; Maremmani, Icro

    2014-02-13

    Alcohol dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Besides psychosocial interventions, different pharmacological interventions have been or currently are under investigation through Cochrane systematic reviews. The primary aim of the review is to assess the benefits/risks of anticonvulsants for the treatment of alcohol dependence. We searched the Cochrane Drugs and Alcohol Group Trials Register (October 2013), PubMed (1966 to October 2013), EMBASE (1974 to October 2013) and CINAHL (1982 to October 2013). Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing anticonvulsants alone or in association with other drugs and/or psychosocial interventions versus placebo, no treatment and other pharmacological or psychosocial interventions. We used standard methodological procedures as expected by The Cochrane Collaboration. A total of 25 studies were included in the review (2641 participants). Most participants were male, with an average age of 44 years. Anticonvulsants were compared with placebo (17 studies), other medications (seven studies) and no medication (two studies). The mean duration of the trials was 17 weeks (range four to 52 weeks). The studies took place in the USA, Europe, South America, India and Thailand. Variation was reported in the characteristics of the studies, including their design and the rating instruments used. For many key outcomes, the risk of bias associated with unclear or unconcealed allocation and lack of blinding affected the quality of the evidence.Anticonvulsants versus placebo: For dropouts (16 studies, 1675 participants, risk ratio (RR) 0.94, 95% confidence interval (Cl) 0.74 to 1.19, moderate-quality evidence) and continuous abstinence (eight studies, 634 participants, RR 1.21, 95% Cl 95% 0.97 to 1.52, moderate-quality evidence), results showed no evidence of differences. Moderate-quality evidence suggested that

  20. Acidification, not carbonation, is the major regulator of carbon fluxes in the coccolithophore Emiliania huxleyi.

    Science.gov (United States)

    Kottmeier, Dorothee M; Rokitta, Sebastian D; Rost, Björn

    2016-07-01

    A combined increase in seawater [CO2 ] and [H(+) ] was recently shown to induce a shift from photosynthetic HCO3 (-) to CO2 uptake in Emiliania huxleyi. This shift occurred within minutes, whereas acclimation to ocean acidification (OA) did not affect the carbon source. To identify the driver of this shift, we exposed low- and high-light acclimated E. huxleyi to a matrix of two levels of dissolved inorganic carbon (1400, 2800 μmol kg(-1) ) and pH (8.15, 7.85) and directly measured cellular O2 , CO2 and HCO3 (-) fluxes under these conditions. Exposure to increased [CO2 ] had little effect on the photosynthetic fluxes, whereas increased [H(+) ] led to a significant decline in HCO3 (-) uptake. Low-light acclimated cells overcompensated for the inhibition of HCO3 (-) uptake by increasing CO2 uptake. High-light acclimated cells, relying on higher proportions of HCO3 (-) uptake, could not increase CO2 uptake and photosynthetic O2 evolution consequently became carbon-limited. These regulations indicate that OA responses in photosynthesis are caused by [H(+) ] rather than by [CO2 ]. The impaired HCO3 (-) uptake also provides a mechanistic explanation for lowered calcification under OA. Moreover, it explains the OA-dependent decrease in photosynthesis observed in high-light grown phytoplankton. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  1. Local dependency in networks

    Directory of Open Access Journals (Sweden)

    Kudĕlka Miloš

    2015-06-01

    Full Text Available Many real world data and processes have a network structure and can usefully be represented as graphs. Network analysis focuses on the relations among the nodes exploring the properties of each network. We introduce a method for measuring the strength of the relationship between two nodes of a network and for their ranking. This method is applicable to all kinds of networks, including directed and weighted networks. The approach extracts dependency relations among the network’s nodes from the structure in local surroundings of individual nodes. For the tasks we deal with in this article, the key technical parameter is locality. Since only the surroundings of the examined nodes are used in computations, there is no need to analyze the entire network. This allows the application of our approach in the area of large-scale networks. We present several experiments using small networks as well as large-scale artificial and real world networks. The results of the experiments show high effectiveness due to the locality of our approach and also high quality node ranking comparable to PageRank.

  2. Detecting positive quadrant dependence and positive function dependence

    NARCIS (Netherlands)

    Janic-Wróblewska, A.; Kallenberg, W.C.M.; Ledwina, T.

    2004-01-01

    There is a lot of interest in positive dependence going beyond linear correlation. In this paper three new rank tests for testing independence against positive dependence are introduced. The first one is directed on positive quadrant dependence, the second and third one concentrate on positive

  3. Detecting positive quadrant dependence and positive function dependence

    NARCIS (Netherlands)

    Janic-Wróblewska, A.; Kallenberg, W.C.M.; Ledwina, T.

    2003-01-01

    There is a lot of interest in positive dependence going beyond linear correlation. In this paper three new rank tests for testing independence against positive dependence are introduced. The first one is directed on positive quadrant dependence, the second and third one concentrate on positive

  4. Context-dependent Generalization

    Directory of Open Access Journals (Sweden)

    Jordan A Taylor

    2013-05-01

    Full Text Available The pattern of generalization following motor learning can provide a probe on the neural mechanisms underlying learning. For example, the breadth of generalization to untrained regions of space after visuomotor adaptation to targets in a restricted region of space has been attributed to the directional tuning properties of neurons in the motor system. Building on this idea, the effect of different types of perturbations on generalization (e.g., rotation versus visual translation have been attributed to the selection of differentially tuned populations. Overlooked in this discussion is consideration of how the context of the training environment may constrain generalization. Here, we explore the role of context by having participants learn a visuomotor rotation or a translational shift in two different contexts, one in which the array of targets were presented in a circular arrangement and the other in which they were presented in a rectilinear arrangement. The perturbation and environments were either consistent (e.g., rotation with circular arrangement or inconsistent (e.g., rotation with rectilinear arrangement. The pattern of generalization across the workspace was much more dependent on the context of the environment than on the perturbation, with broad generalization for the rectilinear arrangement for both types of perturbations. Moreover, the generalization pattern for this context was evident, even when the perturbation was introduced in a gradual manner, precluding the use of an explicit strategy. We describe how current models of generalization might be modified to incorporate these results, building on the idea that context provides a strong bias for how the motor system infers the nature of the visuomotor perturbation and, in turn, how this information influences the pattern of generalization.

  5. Dependent Human Error Probability Assessment

    International Nuclear Information System (INIS)

    Simic, Z.; Mikulicic, V.; Vukovic, I.

    2006-01-01

    This paper presents an assessment of the dependence between dynamic operator actions modeled in a Nuclear Power Plant (NPP) PRA and estimate the associated impact on Core damage frequency (CDF). This assessment was done improve HEP dependencies implementation inside existing PRA. All of the dynamic operator actions modeled in the NPP PRA are included in this assessment. Determining the level of HEP dependence and the associated influence on CDF are the major steps of this assessment. A decision on how to apply the results, i.e., should permanent HEP model changes be made, is based on the resulting relative CDF increase. Some CDF increase was selected as a threshold based on the NPP base CDF value and acceptance guidelines from the Regulatory Guide 1.174. HEP dependence resulting in a CDF increase of > 5E-07 would be considered potential candidates for specific incorporation into the baseline model. The approach used to judge the level of dependence between operator actions is based on dependency level categories and conditional probabilities developed in the Handbook of Human Reliability Analysis with Emphasis on Nuclear Power Plant Applications NUREG/CR-1278. To simplify the process, NUREG/CR-1278 identifies five levels of dependence: ZD (zero dependence), LD (low dependence), MD (moderate dependence), HD (high dependence), and CD (complete dependence). NUREG/CR-1278 also identifies several qualitative factors that could be involved in determining the level of dependence. Based on the NUREG/CR-1278 information, Time, Function, and Spatial attributes were judged to be the most important considerations when determining the level of dependence between operator actions within an accident sequence. These attributes were used to develop qualitative criteria (rules) that were used to judge the level of dependence (CD, HD, MD, LD, ZD) between the operator actions. After the level of dependence between the various HEPs is judged, quantitative values associated with the

  6. Open systems dependability dependability engineering for ever-changing systems

    CERN Document Server

    Tokoro, Mario

    2015-01-01

    The book describes a fundamentally new approach to software dependability, considering a software system as an ever-changing system due to changes in service objectives, users' requirements, standards and regulations, and to advances in technology. Such a system is viewed as an Open System since its functions, structures, and boundaries are constantly changing. Thus, the approach to dependability is called Open Systems Dependability. The DEOS technology realizes Open Systems Dependability. It puts more emphasis on stakeholders' agreement and accountability achievement for business/service cont

  7. Dependent failures of diesel generators

    International Nuclear Information System (INIS)

    Mankamo, T.; Pulkkinen, U.

    1982-01-01

    This survey of dependent failures (common-cause failures) is based on the data of diesel generator failures in U. S. nuclear power plants as reported in Licensee Event Reports. Failures were classified into random and potentially dependent failures. All failures due to design errors, manufacturing or installation errors, maintenance errors, or deviations in the operational environment were classified as potentially dependent failures.The statistical dependence between failures was estimated from the relative portion of multiple failures. Results confirm the earlier view of the significance of statistical dependence, a strong dependence on the age of the diesel generator was found in each failure class excluding random failures and maintenance errors, which had a nearly constant frequency independent of diesel generator age

  8. Partial dependency parsing for Irish

    OpenAIRE

    Uí Dhonnchadha, Elaine; van Genabith, Josef

    2010-01-01

    In this paper we present a partial dependency parser for Irish, in which Constraint Grammar (CG) rules are used to annotate dependency relations and grammatical functions in unrestricted Irish text. Chunking is performed using a regular-expression grammar which operates on the dependency tagged sentences. As this is the first implementation of a parser for unrestricted Irish text (to our knowledge), there were no guidelines or precedents available. Therefore deciding what constitutes a syntac...

  9. Inter-dependence not Over-dependence: Reducing Urban Transport Energy Dependence

    Energy Technology Data Exchange (ETDEWEB)

    Saunders, Michael James; Rodrigues da Silva, Antonio Nelson

    2007-07-01

    A major issue of concern in today's world is urban transport energy dependence and energy supply security. In an energy inter-dependent world, energy over-dependence brings risks to urban transport systems. Many urban areas are over-dependent on finite petroleum resources for transport. New technology and the development and integration of renewable resources into transport energy systems may reduce some of the current transport energy dependence of urban areas. However, the most effective means of reducing energy dependence is to first design urban areas for this condition. An urban policy framework is proposed that requires transport energy dependence to be measured and controlled in the urban development process. A new tool has been created for this purpose, the Transport Energy Specification (TES), which measures transport energy dependence of urban areas. This creates the possibility for cities to regulate urban development with respect to energy dependence. Trial assessments were performed in Germany, New Zealand and Brazil; initial analysis by transport and government professionals shows promise of this tool being included into urban policy. The TES combined with a regulatory framework has the potential to significantly reduce transport energy consumption and dependence in urban areas in the future. (auth)

  10. Two Generations of Path Dependence

    DEFF Research Database (Denmark)

    Madsen, Mogens Ove

      Even if there is no fully articulated and generally accepted theory of Path Dependence it has eagerly been taken up across a wide range of social sciences - primarily coming from economics. Path Dependence is most of all a metaphor that offers reason to believe, that some political, social...

  11. Dependence theory via game theory

    NARCIS (Netherlands)

    Grossi, D.; Turrini, P.

    2011-01-01

    In the multi-agent systems community, dependence theory and game theory are often presented as two alternative perspectives on the analysis of social interaction. Up till now no research has been done relating these two approaches. The unification presented provides dependence theory with the sort

  12. Frequency-dependent heat capacity

    DEFF Research Database (Denmark)

    Behrens, Claus Flensted

    The frequency–dependent heat capacity of super-cooled glycerol near the glass transition is measured using the 3w detection technique. An electrical conducting thin film with a temperature–dependent electrical resistance is deposited on a substrate. The thin film is used simultaneously as a heater...

  13. Density dependent hadron field theory

    International Nuclear Information System (INIS)

    Fuchs, C.; Lenske, H.; Wolter, H.H.

    1995-01-01

    A fully covariant approach to a density dependent hadron field theory is presented. The relation between in-medium NN interactions and field-theoretical meson-nucleon vertices is discussed. The medium dependence of nuclear interactions is described by a functional dependence of the meson-nucleon vertices on the baryon field operators. As a consequence, the Euler-Lagrange equations lead to baryon rearrangement self-energies which are not obtained when only a parametric dependence of the vertices on the density is assumed. It is shown that the approach is energy-momentum conserving and thermodynamically consistent. Solutions of the field equations are studied in the mean-field approximation. Descriptions of the medium dependence in terms of the baryon scalar and vector density are investigated. Applications to infinite nuclear matter and finite nuclei are discussed. Density dependent coupling constants obtained from Dirac-Brueckner calculations with the Bonn NN potentials are used. Results from Hartree calculations for energy spectra, binding energies, and charge density distributions of 16 O, 40,48 Ca, and 208 Pb are presented. Comparisons to data strongly support the importance of rearrangement in a relativistic density dependent field theory. Most striking is the simultaneous improvement of charge radii, charge densities, and binding energies. The results indicate the appearance of a new ''Coester line'' in the nuclear matter equation of state

  14. Dependency in Critically Ill Patients

    Directory of Open Access Journals (Sweden)

    Rumei Yang

    2016-03-01

    Full Text Available By necessity, critically ill patients admitted to intensive care units (ICUs have a high level of dependency, which is linked to a variety of negative feelings, such as powerlessness. However, the term dependency is not well defined in the critically ill patients. The concept of “dependency” in critically ill patients was analyzed using a meta-synthesis approach. An inductive process described by Deborah Finfgeld-Connett was used to analyze the data. Overarching themes emerged that reflected critically ill patients’ experience and meaning of being in dependency were (a antecedents: dependency in critically ill patients was a powerless and vulnerable state, triggered by a life-threatening crisis; (b attributes: the characteristic of losing “self” was featured by dehumanization and disembodiment, which can be alleviated by a “self”-restoring process; and (c outcomes: living with dependency and coping with dependency. The conceptual model explicated here may provide a framework for understanding dependency in critically ill patients.

  15. Evaluating Dependence Criteria for Caffeine.

    Science.gov (United States)

    Striley, Catherine L W; Griffiths, Roland R; Cottler, Linda B

    2011-12-01

    Background: Although caffeine is the most widely used mood-altering drug in the world, few studies have operationalized and characterized Diagnostic and Statistical Manual IV (DSM-IV) substance dependence criteria applied to caffeine. Methods: As a part of a nosological study of substance use disorders funded by the National Institute on Drug Abuse, we assessed caffeine use and dependence symptoms among high school and college students, drug treatment patients, and pain clinic patients who reported caffeine use in the last 7 days and also reported use of alcohol, nicotine, or illicit drugs within the past year ( n =167). Results: Thirty-five percent met the criteria for dependence when all seven of the adopted DSM dependence criteria were used. Rates of endorsement of several of the most applicable diagnostic criteria were as follows: 26% withdrawal, 23% desire to cut down or control use, and 44% continued use despite harm. In addition, 34% endorsed craving, 26% said they needed caffeine to function, and 10% indicated that they talked to a physician or counselor about problems experienced with caffeine. There was a trend towards increased caffeine dependence among those dependent on nicotine or alcohol. Within a subgroup that had used caffeine, alcohol, and nicotine in the past year, 28% fulfilled criteria for caffeine dependence compared to 50% for alcohol and 80% for nicotine. Conclusion: The present study adds to a growing literature suggesting the reliability, validity, and clinical utility of the caffeine dependence diagnosis. Recognition of caffeine dependence in the DSM-V may be clinically useful.

  16. Topology optimised wavelength dependent splitters

    DEFF Research Database (Denmark)

    Hede, K. K.; Burgos Leon, J.; Frandsen, Lars Hagedorn

    A photonic crystal wavelength dependent splitter has been constructed by utilising topology optimisation1. The splitter has been fabricated in a silicon-on-insulator material (Fig. 1). The topology optimised wavelength dependent splitter demonstrates promising 3D FDTD simulation results....... This complex photonic crystal structure is very sensitive against small fabrication variations from the expected topology optimised design. A wavelength dependent splitter is an important basic building block for high-performance nanophotonic circuits. 1J. S. Jensen and O. Sigmund, App. Phys. Lett. 84, 2022...

  17. Mastering Ninject for dependency injection

    CERN Document Server

    Baharestani, Daniel

    2013-01-01

    Mastering Ninject for Dependency Injection teaches you the most powerful concepts of Ninject in a simple and easy-to-understand format using lots of practical examples, diagrams, and illustrations.Mastering Ninject for Dependency Injection is aimed at software developers and architects who wish to create maintainable, extensible, testable, and loosely coupled applications. Since Ninject targets the .NET platform, this book is not suitable for software developers of other platforms. Being familiar with design patterns such as singleton or factory would be beneficial, but no knowledge of depende

  18. Methadone detoxification of tramadol dependence.

    Science.gov (United States)

    Leo, R J; Narendran, R; DeGuiseppe, B

    2000-10-01

    Tramadol hydrochloride is a centrally acting analgesic with a partial affinity for the opiate receptor (mu), having an analgesic potency estimated to be one tenth that of morphine. While preclinical investigations suggested that abuse liability associated with tramadol use is low, there are increasing numbers of cases reported to the U.S. Food and Drug Administration of abuse, dependence, and withdrawal associated with tramadol use. A case of a patient with tramadol dependence requiring detoxification with methadone is presented. Acute management of significant tramadol dependence has not yet been reported in the literature. Long-term treatment issues are also discussed.

  19. A Theory of Service Dependency

    Directory of Open Access Journals (Sweden)

    Mats Neovius

    2016-06-01

    Full Text Available Service composition has become commonplace nowadays, in large part due to the increased complexity of software and supporting networks. Composition can be of many types, for instance sequential, prioritising, non-deterministic. However, a fundamental feature of the services to be composed consists in their dependencies with respect to each other. In this paper we propose a theory of service dependency, modelled around a dependency operator in the Action Systems formalism. We analyze its properties, composition behaviour, and refinement conditions with accompanying examples.

  20. Discovery of Approximate Differential Dependencies

    OpenAIRE

    Liu, Jixue; Kwashie, Selasi; Li, Jiuyong; Ye, Feiyue; Vincent, Millist

    2013-01-01

    Differential dependencies (DDs) capture the relationships between data columns of relations. They are more general than functional dependencies (FDs) and and the difference is that DDs are defined on the distances between values of two tuples, not directly on the values. Because of this difference, the algorithms for discovering FDs from data find only special DDs, not all DDs and therefore are not applicable to DD discovery. In this paper, we propose an algorithm to discover DDs from data fo...

  1. Evaluating Dependence Criteria for Caffeine

    OpenAIRE

    Striley, Catherine L.W.; Griffiths, Roland R.; Cottler, Linda B.

    2011-01-01

    Background: Although caffeine is the most widely used mood-altering drug in the world, few studies have operationalized and characterized Diagnostic and Statistical Manual IV (DSM-IV) substance dependence criteria applied to caffeine. Methods: As a part of a nosological study of substance use disorders funded by the National Institute on Drug Abuse, we assessed caffeine use and dependence symptoms among high school and college students, drug treatment patients, and pain clinic patients who re...

  2. Angular dependence of shallow dose

    International Nuclear Information System (INIS)

    Alvarez, J.L.

    1986-01-01

    The theoretical response of a detector is discussed and compared to measurements of shallow dose with tissue and phantom response detectors. A definite energy dependent angular response of dose and measurement was observed which could not be explained by simple trigonometric arguments. The response is back scatter dependent and must be considered in detector design and dose measurements. It is not possible for standard detectors to follow this response

  3. Scale dependence of deuteron electrodisintegration

    Science.gov (United States)

    More, S. N.; Bogner, S. K.; Furnstahl, R. J.

    2017-11-01

    Background: Isolating nuclear structure properties from knock-out reactions in a process-independent manner requires a controlled factorization, which is always to some degree scale and scheme dependent. Understanding this dependence is important for robust extractions from experiment, to correctly use the structure information in other processes, and to understand the impact of approximations for both. Purpose: We seek insight into scale dependence by exploring a model calculation of deuteron electrodisintegration, which provides a simple and clean theoretical laboratory. Methods: By considering various kinematic regions of the longitudinal structure function, we can examine how the components—the initial deuteron wave function, the current operator, and the final-state interactions (FSIs)—combine at different scales. We use the similarity renormalization group to evolve each component. Results: When evolved to different resolutions, the ingredients are all modified, but how they combine depends strongly on the kinematic region. In some regions, for example, the FSIs are largely unaffected by evolution, while elsewhere FSIs are greatly reduced. For certain kinematics, the impulse approximation at a high renormalization group resolution gives an intuitive picture in terms of a one-body current breaking up a short-range correlated neutron-proton pair, although FSIs distort this simple picture. With evolution to low resolution, however, the cross section is unchanged but a very different and arguably simpler intuitive picture emerges, with the evolved current efficiently represented at low momentum through derivative expansions or low-rank singular value decompositions. Conclusions: The underlying physics of deuteron electrodisintegration is scale dependent and not just kinematics dependent. As a result, intuition about physics such as the role of short-range correlations or D -state mixing in particular kinematic regimes can be strongly scale dependent

  4. Noisy time-dependent spectra

    International Nuclear Information System (INIS)

    Shore, B.W.; Eberly, J.H.

    1983-01-01

    The definition of a time-dependent spectrum registered by an idealized spectrometer responding to a time-varying electromagnetic field as proposed by Eberly and Wodkiewicz and subsequently applied to the spectrum of laser-induced fluorescence by Eberly, Kunasz, and Wodkiewicz is here extended to allow a stochastically fluctuating (interruption model) environment: we provide an algorithm for numerical determination of the time-dependent fluorescence spectrum of an atom subject to excitation by an intense noisy laser and interruptive relaxation

  5. Cyber Epidemic Models with Dependences

    OpenAIRE

    Xu, Maochao; Da, Gaofeng; Xu, Shouhuai

    2016-01-01

    Studying models of cyber epidemics over arbitrary complex networks can deepen our understanding of cyber security from a whole-system perspective. In this paper, we initiate the investigation of cyber epidemic models that accommodate the {\\em dependences} between the cyber attack events. Due to the notorious difficulty in dealing with such dependences, essentially all existing cyber epidemic models have assumed them away. Specifically, we introduce the idea of Copulas into cyber epidemic mode...

  6. Dependência de drogas

    Directory of Open Access Journals (Sweden)

    Miriam Garcia-Mijares

    2006-01-01

    Full Text Available O texto discute três teorias atuais de dependência de drogas: a Teoria Comportamental da dependência como escolha de Heyman, a Teoria da Sensibilização do incentivo de Robinson e Berridge, e a Teoria Neurobiológica da dependência como escolha, de Kalivas. Todas concordam em caracterizar a dependência como resultante de processos de aprendizagem em que droga e estímulos associados a seus efeitos adquirem controle potente sobre o comportamento. Diferenciam-se quanto aos processos de aprendizagem envolvidos. A Teoria Comportamental enfatiza componentes operantes e sustenta que o consumo repetido de drogas diminui o valor reforçador de atividades concorrentes. A Teoria da Sensibilização enfatiza componentes respondentes, propondo a dependência como resultado da sensibilização da potência eliciadora de estímulos condicionados aos efeitos da droga. A Teoria Neurobiológica integra as duas primeiras, descrevendo as mudanças no circuito do reforço que acontecem no processo de dependência.

  7. Spatial dependence of extreme rainfall

    Science.gov (United States)

    Radi, Noor Fadhilah Ahmad; Zakaria, Roslinazairimah; Satari, Siti Zanariah; Azman, Muhammad Az-zuhri

    2017-05-01

    This study aims to model the spatial extreme daily rainfall process using the max-stable model. The max-stable model is used to capture the dependence structure of spatial properties of extreme rainfall. Three models from max-stable are considered namely Smith, Schlather and Brown-Resnick models. The methods are applied on 12 selected rainfall stations in Kelantan, Malaysia. Most of the extreme rainfall data occur during wet season from October to December of 1971 to 2012. This period is chosen to assure the available data is enough to satisfy the assumption of stationarity. The dependence parameters including the range and smoothness, are estimated using composite likelihood approach. Then, the bootstrap approach is applied to generate synthetic extreme rainfall data for all models using the estimated dependence parameters. The goodness of fit between the observed extreme rainfall and the synthetic data is assessed using the composite likelihood information criterion (CLIC). Results show that Schlather model is the best followed by Brown-Resnick and Smith models based on the smallest CLIC's value. Thus, the max-stable model is suitable to be used to model extreme rainfall in Kelantan. The study on spatial dependence in extreme rainfall modelling is important to reduce the uncertainties of the point estimates for the tail index. If the spatial dependency is estimated individually, the uncertainties will be large. Furthermore, in the case of joint return level is of interest, taking into accounts the spatial dependence properties will improve the estimation process.

  8. Extracting Credible Dependencies for Averaged One-Dependence Estimator Analysis

    Directory of Open Access Journals (Sweden)

    LiMin Wang

    2014-01-01

    Full Text Available Of the numerous proposals to improve the accuracy of naive Bayes (NB by weakening the conditional independence assumption, averaged one-dependence estimator (AODE demonstrates remarkable zero-one loss performance. However, indiscriminate superparent attributes will bring both considerable computational cost and negative effect on classification accuracy. In this paper, to extract the most credible dependencies we present a new type of seminaive Bayesian operation, which selects superparent attributes by building maximum weighted spanning tree and removes highly correlated children attributes by functional dependency and canonical cover analysis. Our extensive experimental comparison on UCI data sets shows that this operation efficiently identifies possible superparent attributes at training time and eliminates redundant children attributes at classification time.

  9. Establishment of regression dependences. Linear and nonlinear dependences

    International Nuclear Information System (INIS)

    Onishchenko, A.M.

    1994-01-01

    The main problems of determination of linear and 19 types of nonlinear regression dependences are completely discussed. It is taken into consideration that total dispersions are the sum of measurement dispersions and parameter variation dispersions themselves. Approaches to all dispersions determination are described. It is shown that the least square fit gives inconsistent estimation for industrial objects and processes. The correction methods by taking into account comparable measurement errors for both variable give an opportunity to obtain consistent estimation for the regression equation parameters. The condition of the correction technique application expediency is given. The technique for determination of nonlinear regression dependences taking into account the dependence form and comparable errors of both variables is described. 6 refs., 1 tab

  10. Frequency dependent changes in NMDAR-dependent synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Arvind eKumar

    2011-09-01

    Full Text Available The NMDAR-dependent synaptic plasticity is thought to mediate several forms of learning, and can be induced by spike trains containing a small number of spikes occurring with varying rates and timing, as well as with oscillations. We computed the influence of these variables on the plasticity induced at a single NMDAR containing synapse using a reduced model that was analytically tractable, and these findings were confirmed using detailed, multi-compartment model. In addition to explaining diverse experimental results about the rate and timing dependence of synaptic plasticity, the model made several novel and testable predictions. We found that there was a preferred frequency for inducing long-term potentiation (LTP such that higher frequency stimuli induced lesser LTP, decreasing as 1/f when the number of spikes in the stimulus was kept fixed. Among other things, the preferred frequency for inducing LTP varied as a function of the distance of the synapse from the soma. In fact, same stimulation frequencies could induce LTP or LTD depending on the dendritic location of the synapse. Next, we found that rhythmic stimuli induced greater plasticity then irregular stimuli. Furthermore, brief bursts of spikes significantly expanded the timing dependence of plasticity. Finally, we found that in the ~5-15Hz frequency range both rate- and timing-dependent plasticity mechanisms work synergistically to render the synaptic plasticity most sensitive to spike-timing. These findings provide computational evidence that oscillations can have a profound influence on the plasticity of an NMDAR-dependent synapse, and show a novel role for the dendritic morphology in this process.

  11. A Finite Axiomatization of G-Dependence

    OpenAIRE

    Paolini, Gianluca

    2015-01-01

    We show that a form of dependence known as G-dependence (originally introduced by Grelling) admits a very natural finite axiomatization, as well as Armstrong relations. We also give an explicit translation between functional dependence and G-dependence.

  12. Defining a Cancer Dependency Map.

    Science.gov (United States)

    Tsherniak, Aviad; Vazquez, Francisca; Montgomery, Phil G; Weir, Barbara A; Kryukov, Gregory; Cowley, Glenn S; Gill, Stanley; Harrington, William F; Pantel, Sasha; Krill-Burger, John M; Meyers, Robin M; Ali, Levi; Goodale, Amy; Lee, Yenarae; Jiang, Guozhi; Hsiao, Jessica; Gerath, William F J; Howell, Sara; Merkel, Erin; Ghandi, Mahmoud; Garraway, Levi A; Root, David E; Golub, Todd R; Boehm, Jesse S; Hahn, William C

    2017-07-27

    Most human epithelial tumors harbor numerous alterations, making it difficult to predict which genes are required for tumor survival. To systematically identify cancer dependencies, we analyzed 501 genome-scale loss-of-function screens performed in diverse human cancer cell lines. We developed DEMETER, an analytical framework that segregates on- from off-target effects of RNAi. 769 genes were differentially required in subsets of these cell lines at a threshold of six SDs from the mean. We found predictive models for 426 dependencies (55%) by nonlinear regression modeling considering 66,646 molecular features. Many dependencies fall into a limited number of classes, and unexpectedly, in 82% of models, the top biomarkers were expression based. We demonstrated the basis behind one such predictive model linking hypermethylation of the UBB ubiquitin gene to a dependency on UBC. Together, these observations provide a foundation for a cancer dependency map that facilitates the prioritization of therapeutic targets. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Dependency Structures for Statistical Machine Translation

    Science.gov (United States)

    Bach, Nguyen

    2012-01-01

    Dependency structures represent a sentence as a set of dependency relations. Normally the dependency structures from a tree connect all the words in a sentence. One of the most defining characters of dependency structures is the ability to bring long distance dependency between words to local dependency structures. Another the main attraction of…

  14. Dependence logic theory and applications

    CERN Document Server

    Kontinen, Juha; Väänänen, Jouko; Vollmer, Heribert

    2016-01-01

    In this volume, different aspects of logics for dependence and independence are discussed, including both the logical and computational aspects of dependence logic, and also applications in a number of areas, such as statistics, social choice theory, databases, and computer security. The contributing authors represent leading experts in this relatively new field, each of whom was invited to write a chapter based on talks given at seminars held at the Schloss Dagstuhl Leibniz Center for Informatics in Wadern, Germany (in February 2013 and June 2015) and an Academy Colloquium at the Royal Netherlands Academy of Arts and Sciences (March 2014). Altogether, these chapters provide the most up-to-date look at this developing and highly interdisciplinary field and will be of interest to a broad group of logicians, mathematicians, statisticians, philosophers, and scientists. Topics covered include a comprehensive survey of many propositional, modal, and first-order variants of dependence logic; new results concerning ...

  15. Frequency dependent polarization in blazars

    International Nuclear Information System (INIS)

    Bjoernsson, C.I.

    1984-10-01

    It is argued that the intrinsic frequency dependent polarization in blazars finds its most straightforward explanations in terms of a single rather than a multicomponent sourcemodel. In order to reproduce the observations, under the assumption that the emission mechanism is optically thin synchrotron radiation, both a well ordered magnetic field and an electron distribution with a sharp break or cuttoff are necessary. Non-uniform pitch angle distribution and/or environments where synchrotron losses are important are both conducive to producing strong frequency dependent polarization. Reasons are put forth as to why such conditions ar expected to occur in blazars. Two specific models are discussed in detail and it is shown that they are both able to produce strong frequency dependent polarization, even when the spectral index changes by a small amount only. (orig.)

  16. Developing Tests of Visual Dependency

    Science.gov (United States)

    Kindrat, Alexandra N.

    2011-01-01

    Astronauts develop neural adaptive responses to microgravity during space flight. Consequently these adaptive responses cause maladaptive disturbances in balance and gait function when astronauts return to Earth and are re-exposed to gravity. Current research in the Neuroscience Laboratories at NASA-JSC is focused on understanding how exposure to space flight produces post-flight disturbances in balance and gait control and developing training programs designed to facilitate the rapid recovery of functional mobility after space flight. In concert with these disturbances, astronauts also often report an increase in their visual dependency during space flight. To better understand this phenomenon, studies were conducted with specially designed training programs focusing on visual dependency with the aim to understand and enhance subjects ability to rapidly adapt to novel sensory situations. The Rod and Frame test (RFT) was used first to assess an individual s visual dependency, using a variety of testing techniques. Once assessed, subjects were asked to perform two novel tasks under transformation (both the Pegboard and Cube Construction tasks). Results indicate that head position cues and initial visual test conditions had no effect on an individual s visual dependency scores. Subjects were also able to adapt to the manual tasks after several trials. Individual visual dependency correlated with ability to adapt manual to a novel visual distortion only for the cube task. Subjects with higher visual dependency showed decreased ability to adapt to this task. Ultimately, it was revealed that the RFT may serve as an effective prediction tool to produce individualized adaptability training prescriptions that target the specific sensory profile of each crewmember.

  17. The Copenhagen Dependency Treebank (CDT)

    DEFF Research Database (Denmark)

    Høeg Müller, Henrik; Korzen, Iørn

    2014-01-01

    the fundamentals of how CDT is marked up with semantic relations in accordance with the dependency principles governing the annotation on the other levels of CDT. Specifically, focus will be on how Generative Lexicon (GL) theory has been incorporated into the unitary theoretical dependency framework of CDT....... An annotation scheme for lexical semantics has been designed so as to account for the lexico-semantic structure of complex NPs, and the four GL qualia also appear in some of the CDT discourse relation labels as a description of parallel semantic relations at this level....

  18. Temperature dependence of Brewster's angle.

    Science.gov (United States)

    Guo, Wei

    2018-01-01

    In this work, a dielectric at a finite temperature is modeled as an ensemble of identical atoms moving randomly around where they are trapped. Light reflection from the dielectric is then discussed in terms of atomic radiation. Specific calculation demonstrates that because of the atoms' thermal motion, Brewster's angle is, in principle, temperature-dependent, and the dependence is weak in the low-temperature limit. What is also found is that the Brewster's angle is nothing but a result of destructive superposition of electromagnetic radiation from the atoms.

  19. WITHDRAWN: Carbamazepine for cocaine dependence.

    Science.gov (United States)

    Lima Reisser, Anelise A R L; Silva de Lima, Mauricio; Soares, Bernardo Garcia de Oliveira; Farrell, Michael

    2009-01-21

    Cocaine dependence has become a public health problem, developing a significant number of medical, psychological and social problems. Although there is no consensus regarding how to treat cocaine dependence, effective pharmacotherapy has a potentially major role to play as part of a broader treatment milieu. The anti-convulsant carbamazepine, a tricyclic medication that is widely used to treat a variety of neurological and psychiatric disorders, has been used for treatment of cocaine dependence, although its effectiveness has not been established. To determine whether carbamazepine is effective for the treatment of cocaine dependence. We searched: Cochrane Controlled Trials Register (Cochrane Library issue 1, 1999), MEDLINE (f1966 - October 1997), EMBASE (1980 - October 1997), PsycLIT (1974 - July 1997), Biological Abstracts and LILACS (1982 - 1997); scan of reference list of relevant articles; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. The specialised register of trials of Cochrane Group on Drugs and Alcohol until February 2003. All randomised controlled trials focused on the use of carbamazepine versus placebo on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. The reviewers extracted the data independently, Odds Ratios, weighted mean difference and number needed to treat were estimated. Qualitative assessments of the methodology of eligible studies were carried out using validated checklists. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Where possible analysis was carried out according to the "intention to treat" principles. 5 studies were included (455 participants). No differences regarding positive urine sample for cocaine metabolites. Scores on Spielberg State Anxiety

  20. Dependable Real-Time Systems

    Science.gov (United States)

    1991-09-30

    0196 or 413 545-0720 PI E-mail Address: krithi@nirvan.cs.umass.edu, stankovic(ocs.umass.edu Grant or Contract Title: Dependable Real - Time Systems Grant...Dependable Real - Time Systems " Grant or Contract Number: N00014-85-k-0398 L " Reporting Period: 1 Oct 87 - 30 Sep 91 , 2. Summary of Accomplishments ’ 2.1 Our...in developing a sound approach to scheduling tasks in complex real - time systems , (2) developed a real-time operating system kernel, a preliminary

  1. Parsing Universal Dependencies without training

    DEFF Research Database (Denmark)

    Martínez Alonso, Héctor; Agic, Zeljko; Plank, Barbara

    2017-01-01

    We present UDP, the first training-free parser for Universal Dependencies (UD). Our algorithm is based on PageRank and a small set of specific dependency head rules. UDP features two-step decoding to guarantee that function words are attached as leaf nodes. The parser requires no training......, and it is competitive with a delexicalized transfer system. UDP offers a linguistically sound unsupervised alternative to cross-lingual parsing for UD. The parser has very few parameters and distinctly robust to domain change across languages....

  2. Models for dependent time series

    CERN Document Server

    Tunnicliffe Wilson, Granville; Haywood, John

    2015-01-01

    Models for Dependent Time Series addresses the issues that arise and the methodology that can be applied when the dependence between time series is described and modeled. Whether you work in the economic, physical, or life sciences, the book shows you how to draw meaningful, applicable, and statistically valid conclusions from multivariate (or vector) time series data.The first four chapters discuss the two main pillars of the subject that have been developed over the last 60 years: vector autoregressive modeling and multivariate spectral analysis. These chapters provide the foundational mater

  3. LHCb time-dependent results

    OpenAIRE

    Calvi, Marta

    2011-01-01

    This review reports preliminary results of time-dependent measurements of decays of $B^0$ mesons and $B^0_s$ mesons coming from the analysis of about 36 pb$^{-1}$ of data collected by the LHCb experiment during the 2010 run of the Large Hadron Collider at $\\sqrt{s}$ = 7 TeV.

  4. LHCb time-dependent results

    OpenAIRE

    Calvi, Marta; Collaboration, for the LHCb

    2011-01-01

    This review reports preliminary results of time-dependent measurements of decays of B^0 mesons and B^0_s mesons coming from the analysis of about 36 pb^-1 of data collected by the LHCb experiment during the 2010 run of the Large Hadron Collider at sqrt(s)=7 TeV.

  5. Parsing Universal Dependencies without training

    NARCIS (Netherlands)

    Martínez Alonso, Héctor; Agić, Željko; Plank, Barbara; Søgaard, Anders

    2017-01-01

    We propose UDP, the first training-free parser for Universal Dependencies (UD). Our algorithm is based on PageRank and a small set of head attachment rules. It features two-step decoding to guarantee that function words are attached as leaf nodes. The parser requires no training, and it is

  6. density-dependent selection revisited

    Indian Academy of Sciences (India)

    Unknown

    is a more useful way of looking at density-dependent selection, and then go on ... these models was that the condition for maintenance of ... In a way, their formulation may be viewed as ... different than competition among species, and typical.

  7. Content dependent information flow control

    DEFF Research Database (Denmark)

    Nielson, Hanne Riis; Nielson, Flemming

    2017-01-01

    Information flow control extends access control by not only regulating who is allowed to access what data but also the subsequent use of the data. Applications within communications systems require such information flow control to be dependent on the actual contents of the data. We develop...

  8. Temperature dependence of surface nanobubbles

    NARCIS (Netherlands)

    Berkelaar, R.P.; Seddon, James Richard Thorley; Zandvliet, Henricus J.W.; Lohse, Detlef

    2012-01-01

    The temperature dependence of nanobubbles was investigated experimentally using atomic force microscopy. By scanning the same area of the surface at temperatures from 51 °C to 25 °C it was possible to track geometrical changes of individual nanobubbles as the temperature was decreased.

  9. Sequential Power-Dependence Theory

    NARCIS (Netherlands)

    Buskens, Vincent; Rijt, Arnout van de

    2008-01-01

    Existing methods for predicting resource divisions in laboratory exchange networks do not take into account the sequential nature of the experimental setting. We extend network exchange theory by considering sequential exchange. We prove that Sequential Power-Dependence Theory—unlike

  10. Definition of a Dependent Child

    CERN Multimedia

    Human Resources Department

    2005-01-01

    The Department of Human Resources wishes to remind members of the personnel that, under the provisions of § 6 of Administrative Circular No. 5 “Dependent child”, in the case of a child over 18 years of age the status of dependent child comes to an end once a course of studies is completed. Consequently, the payment of the dependent child allowance and the child's membership of the CERN Health Insurance Scheme terminate with effect from the last day of the month in which the course of study concerned ends. In this connection, members of the personnel are reminded that children who are no longer dependent according to the Staff Rules and Regulations and who are less than 26 years of age can nevertheless opt for membership of the normal health insurance under the terms and conditions laid down in the CERN Health Insurance Rules. The Department of Human Resources also wishes to remind members of the personnel that, pursuant to Article R IV 1.17 of the Staff Regulations, a member of the personnel is requ...

  11. Time dependent view factor methods

    International Nuclear Information System (INIS)

    Kirkpatrick, R.C.

    1998-03-01

    View factors have been used for treating radiation transport between opaque surfaces bounding a transparent medium for several decades. However, in recent years they have been applied to problems involving intense bursts of radiation in enclosed volumes such as in the laser fusion hohlraums. In these problems, several aspects require treatment of time dependence

  12. Directional Dependence in Developmental Research

    Science.gov (United States)

    von Eye, Alexander; DeShon, Richard P.

    2012-01-01

    In this article, we discuss and propose methods that may be of use to determine direction of dependence in non-normally distributed variables. First, it is shown that standard regression analysis is unable to distinguish between explanatory and response variables. Then, skewness and kurtosis are discussed as tools to assess deviation from…

  13. Assessment of groundwater quality and health risk in drinking water basin using GIS.

    Science.gov (United States)

    Şener, Şehnaz; Şener, Erhan; Davraz, Ayşen

    2017-02-01

    Eğirdir Lake basin was selected as the study area because the lake is the second largest freshwater lake in Turkey and groundwater in the basin is used as drinking water. In the present study, 29 groundwater samples were collected and analyzed for physico-chemical parameters to determine the hydrochemical characteristics, groundwater quality, and human health risk in the study area. The dominant ions are Ca 2+ , Mg 2+ , HCO 3 2- , and SO 4 2 . According to Gibbs plot, the predominant samples fall in the rock-water interaction field. A groundwater quality index (WQI) reveals that the majority of the samples falls under good to excellent category of water, suggesting that the groundwater is suitable for drinking and other domestic uses. The Ca-Mg-HCO 3 , Ca-HCO 3 , Ca-SO 4 -HCO 3 , and Ca-Mg-HCO 3 -SO 4 water types are the dominant water types depending on the water-rock interaction in the investigation area. Risk of metals to human health was then evaluated using hazard quotients (HQ) by ingestion and dermal pathways for adults and children. It was indicated that As with HQ ingestion >1 was the most important pollutant leading to non-carcinogenic concerns. It can be concluded that the highest contributors to chronic risks were As and Cr for both adults and children.

  14. State-dependent classical potentials

    International Nuclear Information System (INIS)

    D'Amico, M.

    2001-01-01

    As alternative treatment to the potential operators of standard quantum mechanics is presented. The method is derived from Bohm's mechanics. The operator scalar (V) and vector (A) potential functions are replaced by a quantum potential. It is argued that the classical potential is a special limiting case of a more general quantum potential. The theory is illustrated by deriving an equivalent single-particle equation for the i-th particle of an n-body Bohmian system. The resulting effective state-dependent potential holds the interaction between the single-particle self-wave ψ s and the environment wave ψ e of the n - 1 remaining particles. The effective state-dependent potential is offered as a resolution to the Aharonov-Bohm effect where the phase difference is shown to result from the presence of ψ e . Finally, the interaction between ψ s and ψ e is illustrated graphically

  15. Dependency Ordering of Atomic Observables

    Science.gov (United States)

    Cīrulis, Jānis

    2015-12-01

    The notion of atomic observable was introduced by S.Gudder for effect test spaces in 1997. In this paper an observable is a σ-homomorphism from the Borel algebra on a line to some logic. Roughly, an observable on a logic is atomic, if it is completely determined by its restriction to one-element subsets of its point spectrum. In particular, every discrete observable is atomic. We study some elementary properties of such observables, and discuss a possible notion of functional dependency between them. Algebraically, a dependency is a certain preorder relation on the set of all atomic observables, which induces an order relation on the set of all maximal orthogonal subsets of the logic. Several properties, as well as characteristics in terms of the underlying logic, of these relations are stated.

  16. Direction-dependent exponential biassing

    International Nuclear Information System (INIS)

    Bending, R.C.

    1974-01-01

    When Monte Carlo methods are applied to penetration problems, the use of variance reduction techniques is essential if realistic computing times are to be achieved. A technique known as direction-dependent exponential biassing is described which is simple to apply and therefore suitable for problems with difficult geometry. The material cross section in any region is multiplied by a factor which depends on the particle direction, so that particles travelling in a preferred direction ''see'' a smaller cross section than those travelling in the opposite direction. A theoretical study shows that substantial gains may be obtained, and that the choice of biassing parameter is not critical. The method has been implemented alongside other importance sampling techniques in the general Monte Carlo code SPARTAN, and results obtained for simple problems using this code are included. 4 references. (U.S.)

  17. Temperature dependence of plastic scintillators

    Science.gov (United States)

    Peralta, L.

    2018-03-01

    Plastic scintillator detectors have been studied as dosimeters, since they provide a cost-effective alternative to conventional ionization chambers. Several articles have reported undesired response dependencies on beam energy and temperature, which provides the motivation to determine appropriate correction factors. In this work, we studied the light yield temperature dependency of four plastic scintillators, BCF-10, BCF-60, BC-404, RP-200A and two clear fibers, BCF-98 and SK-80. Measurements were made using a 50 kVp X-ray beam to produce the scintillation and/or radioluminescence signal. The 0 to 40 °C temperature range was scanned for each scintillator, and temperature coefficients were obtained.

  18. Geometry Dependence of Stellarator Turbulence

    International Nuclear Information System (INIS)

    Mynick, H.E.; Xanthopoulos, P.; Boozer, A.H.

    2009-01-01

    Using the nonlinear gyrokinetic code package GENE/GIST, we study the turbulent transport in a broad family of stellarator designs, to understand the geometry-dependence of the microturbulence. By using a set of flux tubes on a given flux surface, we construct a picture of the 2D structure of the microturbulence over that surface, and relate this to relevant geometric quantities, such as the curvature, local shear, and effective potential in the Schrodinger-like equation governing linear drift modes

  19. Reconstructing time-dependent dynamics

    OpenAIRE

    Clemson, Philip; Lancaster, Gemma; Stefanovska, Aneta

    2016-01-01

    The usefulness of the information extracted from biomedical data relies heavily on the underlying theory of the methods used in its extraction. The assumptions of stationarity and autonomicity traditionally applied to dynamical systems break down when considering living systems, due to their inherent time-variability. Living systems are thermodynamically open, and thus constantly interacting with their environment. This results in highly nonlinear, time-dependent dynamics. The aim of signal a...

  20. Fricke xylenol gel energy dependence

    International Nuclear Information System (INIS)

    Costa, Rosangela T.; Moreira, Marcos V.; Almeida, Adelaide de

    2009-01-01

    The advancement of technology has increasingly use the of ionizing radiation mainly in the areas of medicine, industry and research. The development of instruments and methods for an effective performance for detection and measurement of each radiation area was crucial. The literature have demonstrated the effectiveness of the Fricke Xylenol Gel (FXG) as an adequate chemical sensor to be used for dosimetry, once its effective atomic number and density are near to those of the soft tissue. The use of photon beams for therapeutic purpose requires knowledge of their characteristics that can vary for each equipment. Therefore, is important to know all parameters involved for the patient irradiation as the total geometry involved, type of radiation, target material composition and beam energy, that have to be taken into account in the beam dosimetry for the treatment success being the energy parameter is one of the most important. This work was developed to study the energetic dependence of the FXG dosimeter. This chemical solution is made with gelatine 300 Bloom, ferrous ammonium sulfate, xylenol orange, sulfuric acid and Milli-Q water and is based on the Fe +2 oxidation to Fe +3 , due to the ionizing radiation leading to the xylenol orange - ferric complex formation, that is linear depend on the absorbed dose. The FXG samples were irradiated with photons of different energies and the absorbance measurements were done with the spectrophotometric technique at the 585 nm, FXG highest absorption peak. The energetic dependence results presented a stronger dependence for low energies and almost independence for high energies, as expected by the interaction of radiation with matter. (author)

  1. Spin dependent photon structure functions

    International Nuclear Information System (INIS)

    Manohar, A.V.; Massachusetts Inst. of Tech., Cambridge

    1989-01-01

    Spin dependent structure functions of the photon are studied using the operator product expansion. There are new twist-two photon and gluon operators which contribute. The structure functions g 1 and F 3 are calculable in QCD, but differ from their free quark values. The corrections to F 3 are suppressed by 1/log Q 2 . The calculation is an extension of the analysis of Witten for the spin averaged structure functions F 1 and F 2 . (orig.)

  2. Non-transfusion-dependent thalassemias

    Science.gov (United States)

    Musallam, Khaled M.; Rivella, Stefano; Vichinsky, Elliott; Rachmilewitz, Eliezer A.

    2013-01-01

    Non-transfusion-dependent thalassemias include a variety of phenotypes that, unlike patients with beta (β)-thalassemia major, do not require regular transfusion therapy for survival. The most commonly investigated forms are β-thalassemia intermedia, hemoglobin E/β-thalassemia, and α-thalassemia intermedia (hemoglobin H disease). However, transfusion-independence in such patients is not without side effects. Ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process, lead to a variety of subsequent pathophysiologies including iron overload and hypercoagulability that ultimately lead to a number of serious clinical morbidities. Thus, prompt and accurate diagnosis of non-transfusion-dependent thalassemia is essential to ensure early intervention. Although several management options are currently available, the need to develop more novel therapeutics is justified by recent advances in our understanding of the mechanisms of disease. Such efforts require wide international collaboration, especially since non-transfusion-dependent thalassemias are no longer bound to low- and middle-income countries but have spread to large multiethnic cities in Europe and the Americas due to continued migration. PMID:23729725

  3. Genetics Home Reference: pyridoxine-dependent epilepsy

    Science.gov (United States)

    ... Home Health Conditions Pyridoxine-dependent epilepsy Pyridoxine-dependent epilepsy Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Pyridoxine-dependent epilepsy is a condition that involves seizures beginning in ...

  4. Age dependence of tritium metabolism

    International Nuclear Information System (INIS)

    Inaba, Jiro

    1983-01-01

    3 H metabolism in vivo was studied by HTO administration to rats of varying ages for examination of the age dependence of 3 H metabolism in humans. When 1 μCi/g body weight of HTO was administered, the time-course changes of urine 3 H showed definite age dependence; the younger the rat, more rapidly did the 3 H concentration decrease. The biological half-life of whole body residues was about 2 days in nursing offsprings and about 4 days in mature rats. Tissue-bound 3 H showed high and rapid distribution to the liver, whereas it was slow in the brain and muscle, and this tendency was more prominent in younger rats. Compared with 3 H in tissue water, the concentration of bound 3 H was relatively high, being prominent in younger rats. The time-course changes of 3 H concentration from both origins also showed age dependence. The in vivo exposure dose after administration of 1 μCi/g body weight of HTO- 3 H was generally smaller in younger rats, the exposure at ages 10 and 25 days being about a half of that of mature rats. Supposing that human metabolism is similar, the estimated dose in one-year-olds after ingestion of 1 μCi/kg body weight of 3 H in the form of HTO is about 3 times that in adults, and that after 1 μCi/kg body weight of 3 H in infants, about a half of that in adults. (Chiba, N.)

  5. STELLAR MASS DEPENDENT DISK DISPERSAL

    International Nuclear Information System (INIS)

    Kennedy, Grant M.; Kenyon, Scott J.

    2009-01-01

    We use published optical spectral and infrared (IR) excess data from nine young clusters and associations to study the stellar mass dependent dispersal of circumstellar disks. All clusters older than ∼3 Myr show a decrease in disk fraction with increasing stellar mass for solar to higher mass stars. This result is significant at about the 1σ level in each cluster. For the complete set of clusters we reject the null hypothesis-that solar and intermediate-mass stars lose their disks at the same rate-with 95%-99.9% confidence. To interpret this behavior, we investigate the impact of grain growth, binary companions, and photoevaporation on the evolution of disk signatures. Changes in grain growth timescales at fixed disk temperature may explain why early-type stars with IR excesses appear to evolve faster than their later-type counterparts. Little evidence that binary companions affect disk evolution suggests that photoevaporation is the more likely mechanism for disk dispersal. A simple photoevaporation model provides a good fit to the observed disk fractions for solar and intermediate-mass stars. Although the current mass-dependent disk dispersal signal is not strong, larger and more complete samples of clusters with ages of 3-5 Myr can improve the significance and provide better tests of theoretical models. In addition, the orbits of extra-solar planets can constrain models of disk dispersal and migration. We suggest that the signature of stellar mass dependent disk dispersal due to photoevaporation may be present in the orbits of observed extra-solar planets. Planets orbiting hosts more massive than ∼1.6 M sun may have larger orbits because the disks in which they formed were dispersed before they could migrate.

  6. INTENSITY DEPENDENT EFFECTS IN RHIC

    International Nuclear Information System (INIS)

    WEI, J.

    1999-01-01

    The Relativistic Heavy Ion Collider (RHIC) is currently under commissioning after a seven-year construction cycle. Unlike conventional hadron colliders, this machine accelerates, stores, and collides heavy ion beams of various combinations of species. The dominant intensity dependent effects are intra-beam scattering at both injection and storage, and complications caused by crossing transition at a slow ramp rate. In this paper, the authors present theoretical formalisms that have been used for the study, and discuss mechanisms, impacts, and compensation methods including beam cooling and transition jump schemes. Effects of space charge, beam-beam, and ring impedances are also summarized

  7. On scale dependence of hardness

    International Nuclear Information System (INIS)

    Shorshorov, M.Kh.; Alekhin, V.P.; Bulychev, S.I.

    1977-01-01

    The concept of hardness as a structure-sensitive characteristic of a material is considered. It is shown that in conditions of a decreasing stress field under the inventor the hardness function is determined by the average distance, Lsub(a), between the stops (fixed and sessile dislocations, segregation particles, etc.). In the general case, Lsub(a) depends on the size of the impression and explains the great diversity of hardness functions. The concept of average true deformation rate on depression is introduced

  8. Nicotine dependence and psychiatric disorders.

    Science.gov (United States)

    Salín-Pascual, Rafael J; Alcocer-Castillejos, Natasha V; Alejo-Galarza, Gabriel

    2003-01-01

    Nicotine addiction is the single largest preventable cause of morbidity and mortality in the Western World. Smoking is not any more just a bad habit, but a substance addiction problem. The pharmacological aspects of nicotine show that this substance has a broad distribution in the different body compartnents, due mainly to its lipophilic characteristic. There are nicotinic receptors as members of cholinergic receptors' family. They are located in neuromuscular junction and in the central nervous system (CNS). Although they are similar, pentameric structure with an ionic channel to sodium, there are some differences in the protein chains characteristics. Repeated administration of nicotine in rats, results in the sensitization phenomenon, which produces increase in the behavioral locomotor activity response. It has been found that most psychostimulants-induced behavioral sensitization through a nicotine receptor activation. Nicotine receptors in CNS are located mainly in presynaptic membrane and in that way they regulated the release of several neurotransmitters, among them acetylcholine, dopamine, serotonin, and norepinephrine. In some activities like sleep-wake cycle, nicotine receptors have a functional significance. Nicotine receptor stimulation promotes wake time, reduces both, total sleep time and rapid eye movement sleep (REMS). About nicotine dependence, this substance full fills all the criteria for dependence and withdrawal syndrome. There are some people that have more vulnerability for to become nicotine dependent, those are psychiatric patients. Among them schizophrenia, major depression, anxiety disorders and attention deficit disorder, represent the best example in this area. Nicotine may have some beneficial effects, among them are some neuroprotective effects in disorders like Parkinson's disease, and Gilles de la Tourette' syndrome. Also there are several evidences that support the role of nicotine in cognitive improvement functions like attention

  9. Electrogenic sulfate uptake by crustacean hepatopancreatic basolateral membrane vesicles

    International Nuclear Information System (INIS)

    Cattey, M.A.; Gerencser, G.A.; Aheam, G.A.

    1990-01-01

    Basolateral membrane vesicles (BLMV) were isolated from Atlantic lobster (Homarus americanus) hepatopancreas and purified by discontinuous sucrose gradient centrifugation. BLMV prepared in this fashion were osmotically reactive exhibiting linear dependence of vesicular 35 SO 4 -2 uptake to increasing external osmotic pressure with negligible non-specific isotope binding. Under short circuited conditions (valinomycin/K + ) BLMV responded to either a HCO 3 - gradient directed out or equilibrated HCO 3 - (10 mM) by displaying short term accumulation of sulfate above that of equilibrium. Uptake of divalent anion was unaffected by an inwardly directed transmembrane Na + or tetramethylammonium + gradient. 35 SO 4 -2 /HCO 3 - exchange in the presence of valinomycin was stimulated by transient inside positive K + diffusion potentials and inhibited by transient inside negative K + diffusion potentials. The role of electrogenic anion exchange by hepatopancreas BLMV in transcellular sulfate transport is discussed

  10. The effect of tanespimycin (17-AAG) on radioiodine accumulation in sodium iodide symporter expressing cells

    International Nuclear Information System (INIS)

    Yu, Kyoung Hyun; Youn, Hyewon; Song, Myung Geun; Lee, Dong Soo; Chung, June Key

    2012-01-01

    The heat shock protein 90 inhibitor, tanespimycin, is an anticancer agent known to increase iodine accumulation in normal and cancerous thyroid cells. Iodine accumulation is regulated by membrane proteins such as sodium iodide sym porter (NIS) and pendrin (PDS), and thus we attempted to characterize the effects of tanespimycin on those genes. Cells were incubated with tanespimycin in order to evaluate 125 I accumulation and efflux ability. Radioiodine uptake and efflux were measured by a gamma counter and normalized by protein amount. RT PCR were performed to measure the level of gene expression. After tanespimycin treatment, 125 uptake was in creased by ∼2.5 fold in FRTL 5, hNIS ARO. and hNIS MDA MB 231 cells, but no changes were detected in the hNIS HeLa cells. Tanespimycin significantly reduced the radioiodine efflux rate only in the FRTL 5 cell. in the FRTL 5 and hNIS ARO cells, PDS mRNA levels were markedly reduced; the only other observed alteration in the levels of NIS mRNA after tanespimtycin treatment was an observed increase in the h hNIS ARO cells. These results indicate that cellular responses against tanespimycin treatment differed between the normal rat thyroid cells and human cancer cells, and the reduction in the 125I efflux rate by tanespimycin in the normal rat thyroid cells might be attributable to reduced PDS gene expression

  11. Sodium Iodide Symporter Gene Transfer for Imaging and Ablation of Prostate Cancer

    National Research Council Canada - National Science Library

    Jhiang, Sissy M

    2005-01-01

    .... The specific aims of this project are to: (1) confirm metastatic progression to distant lymph nodes and lungs following subcutaneous inoculation of rats with MATLyLu prostatic adenocarcinoma cells expressing hNIS; (2...

  12. Genetically Targeted Radiotherapy Utilizing the Human Sodium Iodide Symporter in Human Breast Carcinoma Cells

    National Research Council Canada - National Science Library

    Krager, Kimberly; Domann, Frederick E

    2006-01-01

    .... Clones were grown and are currently being screen for radioactive accumulation. The stable NIS-expressing cells will then be utilized in determining the level of NIS expression necessary to elicit a bystander effect...

  13. Osmotolerance of Dekkera bruxellensis and the role of two Stl glycerol–proton symporters

    Czech Academy of Sciences Publication Activity Database

    Zemančíková, Jana; Dušková, Michala; Elicharová, Hana; Papoušková, Klára; Sychrová, Hana

    2018-01-01

    Roč. 365, č. 5 (2018), č. článku fny020. ISSN 0378-1097 R&D Projects: GA ČR(CZ) GA15-03708S Institutional support: RVO:67985823 Keywords : glycerol uptake * osmotolerance * non-conventional yeasts Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 1.765, year: 2016

  14. Sodium Iodide Symporter PET and BLI Noninvasively Reveal Mesoangioblast Survival in Dystrophic Mice

    Directory of Open Access Journals (Sweden)

    Bryan Holvoet

    2015-12-01

    Full Text Available Muscular dystrophies are a heterogeneous group of myopathies, characterized by muscle weakness and degeneration, without curative treatment. Mesoangioblasts (MABs have been proposed as a potential regenerative therapy. To improve our understanding of the in vivo behavior of MABs and the effect of different immunosuppressive therapies, like cyclosporine A or co-stimulation-adhesion blockade therapy, on cell survival noninvasive cell monitoring is required. Therefore, cells were transduced with a lentiviral vector encoding firefly luciferase (Fluc and the human sodium iodide transporter (hNIS to allow cell monitoring via bioluminescence imaging (BLI and small-animal positron emission tomography (PET. Non-H2 matched mMABs were injected in the femoral artery of dystrophic mice and were clearly visible via small-animal PET and BLI. Based on noninvasive imaging data, we were able to show that co-stim was clearly superior to CsA in reducing cell rejection and this was mediated via a reduction in cytotoxic T cells and upregulation of regulatory T cells.

  15. Video context-dependent recall.

    Science.gov (United States)

    Smith, Steven M; Manzano, Isabel

    2010-02-01

    In two experiments, we used an effective new method for experimentally manipulating local and global contexts to examine context-dependent recall. The method included video-recorded scenes of real environments, with target words superimposed over the scenes. In Experiment 1, we used a within-subjects manipulation of video contexts and compared the effects of reinstatement of a global context (15 words per context) with effects of less overloaded context cues (1 and 3 words per context) on recall. The size of the reinstatement effects in Experiment 1 show how potently video contexts can cue recall. A strong effect of cue overload was also found; reinstatement effects were smaller, but still quite robust, in the 15 words per context condition. The powerful reinstatement effect was replicated for local contexts in Experiment 2, which included a no-contexts-reinstated group, a control condition used to determine whether reinstatement of half of the cues caused biased output interference for uncued targets. The video context method is a potent way to investigate context-dependent memory.

  16. Oxygen dependency of porfiromycin cytotoxicity

    International Nuclear Information System (INIS)

    Marshall, R.S.; Rauth, A.M.

    1987-01-01

    The authors determined the oxygen dependency of toxicity for the bioreductive alkylating agents mitomycin C (MMC) and porfiromycin (PM) to investigate whether the toxicities of these agents increase in the range of oxygen tensions over which cells become increasingly radioresistant. In the present work the oxygen dependency of PM in CHO cells was determined by assaying survival as a function of time of exposure to 1.0 μg/ml PM under various known levels of oxygen. While PM demonstrated preferential hypoxic cell toxicity, aerobic cell survival was reduced ten-fold after five hours of exposure. Conversely, PM toxicity after a five hour hypoxic exposure to <0.001% oxygen appeared to be greater than that observed for similar MMC exposures, suggesting that PM may be more selective than MMC in killing hypoxic rather than aerobic cells. The authors are currently investigating this preferential toxicity in two human cell lines, one of which is resistant to these agents. At present, these observations suggest that PM may be more effective than MMC at destroying tumour cells in regions of intermediate and low oxygen tensions which may survive radiotherapy, though the range of oxygen tensions which mediate toxicity is similar for both agents

  17. Wavelength dependence of interstellar polarization

    International Nuclear Information System (INIS)

    Mavko, G.E.

    1974-01-01

    The wavelength dependence of interstellar polarization was measured for twelve stars in three regions of the Milky Way. A 120A bandpass was used to measure the polarization at a maximum of sixteen wavelengths evenly spaced between 2.78μ -1 (3600A) and 1.28μ -1 (7800A). For such a wide wavelength range, the wavelength resolution is superior to that of any previously reported polarization measurements. The new scanning polarimeter built by W. A. Hiltner of the University of Michigan was used for the observations. Very broad structure was found in the wavelength dependence of the polarization. Extensive investigations were carried out to show that the structure was not caused by instrumental effects. The broad structure observed is shown to be in agreement with concurrent extinction measurements for the same stars. Also, the observed structure is of the type predicted when a homogeneous silicate grain model is fitted to the observed extinction. The results are in agreement with the hypothesis that the very broad band structure seen in the extinction is produced by the grains. (Diss. Abstr. Int., B)

  18. Selfsimilar time dependent shock structures

    International Nuclear Information System (INIS)

    Beck, R.; Drury, L.O.

    1985-01-01

    Diffusive shock acceleration as an astrophysical mechanism for accelerating charged particles has the advantage of being highly efficient. This means however that the theory is of necessity nonlinear; the reaction of the accelerated particles on the shock structure and the acceleration process must be self-consistently included in any attempt to develop a complete theory of diffusive shock acceleration. Considerable effort has been invested in attempting, at least partially, to do this and it has become clear that in general either the maximum particle energy must be restricted by introducing additional loss processes into the problem or the acceleration must be treated as a time dependent problem (Drury, 1984). It is concluded that stationary modified shock structures can only exist for strong shocks if additional loss processes limit the maximum energy a particle can attain. This is certainly possible and if it occurs the energy loss from the shock will lead to much greater shock compressions. It is however equally possible that no such processes exist and we must then ask what sort of nonstationary shock structure develops. The same argument which excludes stationary structures also rules out periodic solutions and indeed any solution where the width of the shock remains bounded. It follows that the width of the shock must increase secularly with time and it is natural to examine the possibility of selfsimilar time dependent solutions

  19. Selfsimilar time dependent shock structures

    Science.gov (United States)

    Beck, R.; Drury, L. O.

    1985-01-01

    Diffusive shock acceleration as an astrophysical mechanism for accelerating charged particles has the advantage of being highly efficient. This means however that the theory is of necessity nonlinear; the reaction of the accelerated particles on the shock structure and the acceleration process must be self-consistently included in any attempt to develop a complete theory of diffusive shock acceleration. Considerable effort has been invested in attempting, at least partially, to do this and it has become clear that in general either the maximum particle energy must be restricted by introducing additional loss processes into the problem or the acceleration must be treated as a time dependent problem (Drury, 1984). It is concluded that stationary modified shock structures can only exist for strong shocks if additional loss processes limit the maximum energy a particle can attain. This is certainly possible and if it occurs the energy loss from the shock will lead to much greater shock compressions. It is however equally possible that no such processes exist and we must then ask what sort of nonstationary shock structure develops. The ame argument which excludes stationary structures also rules out periodic solutions and indeed any solution where the width of the shock remains bounded. It follows that the width of the shock must increase secularly with time and it is natural to examine the possibility of selfsimilar time dependent solutions.

  20. Voltage Dependence of Supercapacitor Capacitance

    Directory of Open Access Journals (Sweden)

    Szewczyk Arkadiusz

    2016-09-01

    Full Text Available Electronic Double-Layer Capacitors (EDLC, called Supercapacitors (SC, are electronic devices that are capable to store a relatively high amount of energy in a small volume comparing to other types of capacitors. They are composed of an activated carbon layer and electrolyte solution. The charge is stored on electrodes, forming the Helmholtz layer, and in electrolyte. The capacitance of supercapacitor is voltage- dependent. We propose an experimental method, based on monitoring of charging and discharging a supercapacitor, which enables to evaluate the charge in an SC structure as well as the Capacitance-Voltage (C-V dependence. The measurement setup, method and experimental results of charging/discharging commercially available supercapacitors in various voltage and current conditions are presented. The total charge stored in an SC structure is proportional to the square of voltage at SC electrodes while the charge on electrodes increases linearly with the voltage on SC electrodes. The Helmholtz capacitance increases linearly with the voltage bias while a sublinear increase of total capacitance was found. The voltage on SC increases after the discharge of electrodes due to diffusion of charges from the electrolyte to the electrodes. We have found that the recovery voltage value is linearly proportional to the initial bias voltage value.

  1. Kinetic study of the hydration of propylene oxide in the presence of heterogeneous catalyst

    Directory of Open Access Journals (Sweden)

    Akyalcin Sema

    2017-01-01

    Full Text Available The kinetics of the hydration of propylene oxide was studied using a pressurized batch reactor for both uncatalyzed and heterogeneously catalyzed reactions. Lewatit MonoPlus M500/HCO3 - was used as heterogeneous catalyst, which showed better performance than Dowex Marathon A/HCO3 -. The effects of the parameters, namely internal and external diffusion resistances, temperature, catalyst loading and mole ratios of reactants, on the reaction rate were studied. The uncatalyzed and heterogeneously catalyzed reactions were proven to follow a series-parallel irreversible homogeneous mechanism. The temperature dependencies of the rate constants appearing in the rate expressions were determined.

  2. Psychiatric disorders in opioid dependants.

    Science.gov (United States)

    Ahmadi, Jamshid; Toobaee, Shahin; Kharras, Mohammad; Radmehr, Mohammad

    2003-09-01

    Psychiatric disorders are common among substance dependants. The objectives of this study were to assess the rate of neurotic disorders among opioid addicts, and reassess the rate of those neurotic disorders two weeks after complete detoxification of the patients. Data were gathered from 500 (496 men and 4 women) opioid dependants, using DSM-IV criteria. The Middlesex Hospital Questionnaire (MHQ) was used to measure free-floating anxiety, depression, phobia, obsession, hysteria and somatization. Four hundred and ninety-six (99.2%) of the subjects were men of whom the majority (65.2%) were married, 26.4% single and the others were divorced or separated. Three hundred and thirty-four (66.8%) were in age range of 20 to 39 years. Of the subjects 154 (30.8) were self-employed, 116 (23.2%) were factory workers, 100 (20%) unemployed, 64 (12.8%) employees and 32 (6.4%) retailers. The majority, 322 (64.4%), reported elementary and high school as their level of education and only 20 (4%) were illiterate. The means for neurotic disorders (using the MHQ) before and two weeks after detoxification were 10.12 and 9.98 for anxiety, 7.54 and 7.41 for phobia, 10.10 and 9.76 for depression, 11.11 and 11.05 for obsession, 8.47 and 8.49 for hysteria and 9.82 and 9.46 for somatization, respectively. The mean difference was significant only for depression. Present findings indicated that the rate of neurotic disorders in opioid dependants is high and (except for depression) was not significantly different before detoxification and two weeks after detoxification. Opium was found to be the most prevalent form of opioid used. Also it can be concluded that during the last years some demographic characteristics of Iranian opioid addicts in this sample have changed. Cultural attitudes toward substance use quite likely affect the pattern of substance use. These findings can be considered when planning preventive and therapeutic programs.

  3. Dynamic Dependence and Diversification in Corporate Credit

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Jacobs, Kris; Jin, Xisong

    We characterize dependence and tail dependence in corporate credit using a new class of dynamic copula models which can capture dynamic dependence and asymmetry in large samples of firms. We also document important differences between the dependence dynamics for credit spreads and equity returns...

  4. Suicidal Behavior in Chemically Dependent Adolescents.

    Science.gov (United States)

    Cavaiola, Alan A.; Lavender, Neil

    1999-01-01

    Study explores distinctions between chemically dependent suicide attempters, chemically dependent nonsuicidal adolescents, and high school students with no history of chemical dependency (N=250). Results reveal that there were significant differences between the chemically dependent groups. It was also found that the majority of suicidal gestures…

  5. Chameleons with Field Dependent Couplings

    CERN Document Server

    Brax, Philippe; Mota, David F; Nunes, Nelson J; Winther, Hans A

    2010-01-01

    Certain scalar-tensor theories exhibit the so-called chameleon mechanism, whereby observational signatures of scalar fields are hidden by a combination of self-interactions and interactions with ambient matter. Not all scalar-tensor theories exhibit such a chameleon mechanism, which has been originally found in models with inverse power run-away potentials and field independent couplings to matter. In this paper we investigate field-theories with field-dependent couplings and a power-law potential for the scalar field. We show that the theory indeed is a chameleon field theory. We find the thin-shell solution for a spherical body and investigate the consequences for E\\"ot-Wash experiments, fifth-force searches and Casimir force experiments. Requiring that the scalar-field evades gravitational tests, we find that the coupling is sensitive to a mass-scale which is of order of the Hubble scale today.

  6. Epistemic dependence in interdisciplinary groups

    DEFF Research Database (Denmark)

    Andersen, Hanne; Wagenknecht, Susann

    2013-01-01

    In interdisciplinary research scientists have to share and integrate knowledge between people and across disciplinary boundaries. An important issue for philosophy of science is to understand how scientists who work in these kinds of environments exchange knowledge and develop new concepts...... and theories across diverging fields. There is a substantial literature within social epistemology that discusses the social aspects of scientific knowledge, but so far few attempts have been made to apply these resources to the analysis of interdisciplinary science. Further, much of the existing work either...... ignores the issue of differences in background knowledge, or it focuses explicitly on conflicting background knowledge. In this paper we provide an analysis of the interplay between epistemic dependence between individual experts with different areas of expertise. We analyze the cooperative activity...

  7. Glucose-dependent insulinotropic polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel Bring

    2016-01-01

    was to investigate how the blood glucose level affects the glucagon and insulin responses to GIP in healthy subjects (Study 1) and patients with Type 2 diabetes (Study 2), and more specifically to investigate the effects of GIP and GLP-1 at low blood glucose in patients with Type 1 diabetes without endogenous...... as his own control. Interventions were intravenous administration of hormones GIP, GLP-1 and placebo (saline) during different blood glucose levels maintained (clamped) at a certain level. The end-points were plasma concentrations of glucagon and insulin as well as the amount of glucose used to clamp...... the blood glucose levels. In Study 3, we also used stable glucose isotopes to estimate the endogenous glucose production and assessed symptoms and cognitive function during hypoglycaemia. The results from the three studies indicate that GIP has effects on insulin and glucagon responses highly dependent upon...

  8. Glucose-dependent Insulinotropic Polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel B; Calanna, Salvatore; Holst, Jens Juul

    2014-01-01

    CONTEXT: Patients with type 2 diabetes mellitus (T2DM) have clinically relevant disturbances in the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP). OBJECTIVE: We aimed to evaluate the importance of the prevailing plasma glucose levels for the effect of GIP on responses......: During fasting glycemia (plasma glucose ∼8 mmol/L), GIP elicited significant increments in both insulin and glucagon levels, resulting in neutral effects on plasma glucose. During insulin-induced hypoglycemia (plasma glucose ∼3 mmol/L), GIP elicited a minor early-phase insulin response and increased...... glucagon levels during the initial 30 minutes, resulting in less glucose needed to be infused to maintain the clamp (29 ± 8 vs 49 ± 12 mg × kg(-1), P glucose ∼12 mmol/L), GIP augmented insulin secretion throughout the clamp, with slightly less glucagon...

  9. Autonomia versus dependência

    OpenAIRE

    Coutinho, Nelma de Jesus Penela

    2016-01-01

    Relatório de estágio realizado no âmbito do mestrado em Psicologia Clínica. Exame público realizado em 27 de Abril de 2012. O tema das adicções sempre me fomentou uma curiosidade face à relação que o indivíduo tem com a substância! objecto. Se por um lado o ser humano aprende a tornar-se num ser autónomo durante o seu crescimento, desvinculando-se dos seus progenitores para se tornar independente, por outro lado, existem experiências que o conduzem para a estrada da dependência, não de ...

  10. Betweenness in time dependent networks

    International Nuclear Information System (INIS)

    Alsayed, Ahmad; Higham, Desmond J.

    2015-01-01

    The concept of betweenness has given rise to a very useful class of network centrality measures. Loosely, betweenness quantifies the level of importance of a node in terms of its propensity to act as an intermediary when messages are passed around the network. In this work we generalize a walk-based betweenness measure to the case of time-dependent networks, such as those arising in telecommunications and on-line social media. We also introduce a new kind of betweenness measure, temporal betweenness, which quantifies the importance of a time-point. We illustrate the effectiveness of these new measures on synthetic examples, and also give results on real data sets involving voice call, email and Twitter

  11. [Abuse, dependence and intoxication of substances].

    Science.gov (United States)

    Wada, Kiyoshi

    2015-09-01

    As for substance-related disorders, there were several differences between ICD-10 and DSM-IV, however, the concept of "dependence" had been essential for both criteria. DSM-5 published in 2013 had erased dependence. This confuses us. It is important to recognize dependence again. "Abuse" is the self-intake behavior of drug against the social norms. Repeated abuse results in dependence. Dependence is a state of loss of control against drug use due to craving. Abuse can produce "acute intoxication", and repeated abuse under dependence can produce "chronic intoxication". It is important to understand abuse, dependence and "intoxication" based on their relationship from the point of time course.

  12. Analysis of Critical Infrastructure Dependencies and Interdependencies

    Energy Technology Data Exchange (ETDEWEB)

    Petit, Frederic [Argonne National Lab. (ANL), Argonne, IL (United States); Verner, Duane [Argonne National Lab. (ANL), Argonne, IL (United States); Brannegan, David [Argonne National Lab. (ANL), Argonne, IL (United States); Buehring, William [Argonne National Lab. (ANL), Argonne, IL (United States); Dickinson, David [Argonne National Lab. (ANL), Argonne, IL (United States); Guziel, Karen [Argonne National Lab. (ANL), Argonne, IL (United States); Haffenden, Rebecca [Argonne National Lab. (ANL), Argonne, IL (United States); Phillips, Julia [Argonne National Lab. (ANL), Argonne, IL (United States); Peerenboom, James [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-06-01

    The report begins by defining dependencies and interdependencies and exploring basic concepts of dependencies in order to facilitate a common understanding and consistent analytical approaches. Key concepts covered include; Characteristics of dependencies: upstream dependencies, internal dependencies, and downstream dependencies; Classes of dependencies: physical, cyber, geographic, and logical; and Dimensions of dependencies: operating environment, coupling and response behavior, type of failure, infrastructure characteristics, and state of operations From there, the report proposes a multi-phase roadmap to support dependency and interdependency assessment activities nationwide, identifying a range of data inputs, analysis activities, and potential products for each phase, as well as key steps needed to progress from one phase to the next. The report concludes by outlining a comprehensive, iterative, and scalable framework for analyzing dependencies and interdependencies that stakeholders can integrate into existing risk and resilience assessment efforts.

  13. Bioinspired orientation-dependent friction.

    Science.gov (United States)

    Xue, Longjian; Iturri, Jagoba; Kappl, Michael; Butt, Hans-Jürgen; del Campo, Aránzazu

    2014-09-23

    Spatular terminals on the toe pads of a gecko play an important role in directional adhesion and friction required for reversible attachment. Inspired by the toe pad design of a gecko, we study friction of polydimethylsiloxane (PDMS) micropillars terminated with asymmetric (spatular-shaped) overhangs. Friction forces in the direction of and against the spatular end were evaluated and compared to friction forces on symmetric T-shaped pillars and pillars without overhangs. The shape of friction curves and the values of friction forces on spatula-terminated pillars were orientation-dependent. Kinetic friction forces were enhanced when shearing against the spatular end, while static friction was stronger in the direction toward the spatular end. The overall friction force was higher in the direction against the spatula end. The maximum value was limited by the mechanical stability of the overhangs during shear. The aspect ratio of the pillar had a strong influence on the magnitude of the friction force, and its contribution surpassed and masked that of the spatular tip for aspect ratios of >2.

  14. Dependency Parsing with Transformed Feature

    Directory of Open Access Journals (Sweden)

    Fuxiang Wu

    2017-01-01

    Full Text Available Dependency parsing is an important subtask of natural language processing. In this paper, we propose an embedding feature transforming method for graph-based parsing, transform-based parsing, which directly utilizes the inner similarity of the features to extract information from all feature strings including the un-indexed strings and alleviate the feature sparse problem. The model transforms the extracted features to transformed features via applying a feature weight matrix, which consists of similarities between the feature strings. Since the matrix is usually rank-deficient because of similar feature strings, it would influence the strength of constraints. However, it is proven that the duplicate transformed features do not degrade the optimization algorithm: the margin infused relaxed algorithm. Moreover, this problem can be alleviated by reducing the number of the nearest transformed features of a feature. In addition, to further improve the parsing accuracy, a fusion parser is introduced to integrate transformed and original features. Our experiments verify that both transform-based and fusion parser improve the parsing accuracy compared to the corresponding feature-based parser.

  15. Psychobiological mechanisms of exercise dependence.

    Science.gov (United States)

    Hamer, Mark; Karageorghis, Costas I

    2007-01-01

    Exercise dependence (ED) is characterised by an obsessive and unhealthy preoccupation with exercise. Previous research has focused largely on identifying behavioural aspects of ED, although the biological mechanisms remain unknown and are under researched. We review various ED hypotheses including affect regulation, anorexia analogue, sympathetic arousal and beta-endorphin. We also present a novel hypothesis pertaining to ED and interleukin (IL)-6, which combines previous hypotheses with literature from the field of psycho-neuroimmunology. We explore the notion that IL-6 provides a link from the periphery to the brain, which may mediate the underlying features of ED. We propose a conceptual model indicating that, in individuals prone to ED, exercise results in a transient reduction in negative affect, but concurrently results in excessive production of IL-6 and the activation of neuroendocrine pathways, which are associated with behavioural and psychological disturbances of exercise withdrawal. Our intention is for this model to serve as a basis for further research in the area of ED, which may eventually lead to the development of successful treatment strategies. Recent developments in methods to reliably assess these biological markers from blood and saliva samples should encourage such research to be undertaken in exercise settings.

  16. Directional dependency of air sampling

    International Nuclear Information System (INIS)

    1994-01-01

    A field study was performed by Idaho State University-Environmental Monitoring Laboratory (EML) to examine the directional dependency of low-volume air samplers. A typical continuous low volume air sampler contains a sample head that is mounted on the sampler housing either horizontally through one of four walls or vertically on an exterior wall 'looking down or up.' In 1992, a field study was undertaken to estimate sampling error and to detect the directional effect of sampler head orientation. Approximately 1/2 mile downwind from a phosphate plant (continuous source of alpha activity), four samplers were positioned in identical orientation alongside one sampler configured with the sample head 'looking down'. At least five consecutive weekly samples were collected. The alpha activity, beta activity, and the Be-7 activity collected on the particulate filter were analyzed to determine sampling error. Four sample heads were than oriented to the four different horizontal directions. Samples were collected for at least five weeks. Analysis of the alpha data can show the effect of sampler orientation to a know near source term. Analysis of the beta and Be-7 activity shows the effect of sampler orientation to a ubiquitous source term

  17. Italy's recurrent energy dependency dilemma

    International Nuclear Information System (INIS)

    Ippolito, F.

    1993-01-01

    This paper first critically assesses the objectives of Italy's 1988 National Energy Plan which, in light of the moratorium on nuclear energy, called for moderate but steady reductions in imported energy supplies through the implementation of energy conservation programs and the development of available domestic conventional and renewable energy sources. The economics and energy analyses evidence that, in view this nation's current troubled economic situation, the Energy Plan's target for the year 2000 of a 76% dependency on foreign oil is just not good enough and not in line with stricter European environmental normatives limiting carbon dioxide emissions. It is argued that in order to effectively reduce the nation's excessively high energy costs, keep pace with other industrialized countries in a highly competitive market (Italy's energy tariffs are almost 55% greater than those of Germany and France), and to respect new European anti-pollution laws, Italy must restart its nuclear program and take advantage of the recent advances being made in passive reactor safety systems

  18. DEPONTO: A Reusable Dependability Domain Ontology

    Directory of Open Access Journals (Sweden)

    Teodora Sanislav

    2015-08-01

    Full Text Available This paper proposes a dependability reusable ontology for knowledge representation. The fundamental knowledge related to dependability follows its taxonomy. Thus, this paper gives an analysis of what is the dependability domain ontology andof its components.The dependability domain ontology plays an important role in ensuring the dependability of information systems by providing support for their diagnosis in case of faults, errors and failures.The proposed ontology is used as a dependability framework in two case study Cyber-Physical Systemswhich demonstrate its reusability within this category of systems.

  19. Observed and predicted reproduction of Ceriodaphnia dubia exposed to chloride, sulfate, and bicarbonate

    Science.gov (United States)

    Lasier, Peter J.; Hardin, Ian R.

    2010-01-01

    Chronic toxicities of Cl-, SO42-, and HCO3- to Ceriodaphnia dubia were evaluated in low- and moderate-hardness waters using a three-brood reproduction test method. Toxicity tests of anion mixtures were used to determine interaction effects and to produce models predicting C. dubia reproduction. Effluents diluted with low- and moderate-hardness waters were tested with animals acclimated to low- and moderate-hardness conditions to evaluate the models and to assess the effects of hardness and acclimation. Sulfate was significantly less toxic than Cl- and HCO3- in both types of water. Chloride and HCO3- toxicities were similar in low-hardness water, but HCO3- was the most toxic in moderate-hardness water. Low acute-to-chronic ratios indicate that toxicities of these anions will decrease quickly with dilution. Hardness significantly reduced Cl- and SO42- toxicity but had little effect on HCO3-. Chloride toxicity decreased with an increase in Na+ concentration, and CO3- toxicity may have been reduced by the dissolved organic carbon in effluent. Multivariate models using measured anion concentrations in effluents with low to moderate hardness levels provided fairly accurate predictions of reproduction. Determinations of toxicity for several effluents differed significantly depending on the hardness of the dilution water and the hardness of the water used to culture test animals. These results can be used to predict the contribution of elevated anion concentrations to the chronic toxicity of effluents; to identify effluents that are toxic due to contaminants other than Cl-, SO42-, and HCO3-; and to provide a basis for chemical substitutions in manufacturing processes.

  20. Modeling dependencies in product families with COVAMOF

    NARCIS (Netherlands)

    Sinnema, Marco; Deelstra, Sybren; Nijhuis, Jos; Bosch, Jan; Riebisch, M; Tabeling, P; Zorn, W

    2006-01-01

    Many variability modeling approaches consider only formalized dependencies, i.e. in- or exclude relations between variants. However, in real industrial product families, dependencies are often much more complicated. In this paper, we discuss the product derivation problems associated with

  1. National Council on Alcoholism and Drug Dependence

    Science.gov (United States)

    ... Month NCADD National Council on Alcoholism and Drug Dependence Addiction is a Disease - Treatment is Available - Recovery ... years, The National Council on Alcoholism and Drug Dependence, Inc. (NCADD) has been a valuable resource for ...

  2. Isospin dependent properties of asymmetric nuclear matter

    OpenAIRE

    Chowdhury, P. Roy; Basu, D. N.; Samanta, C.

    2009-01-01

    The density dependence of nuclear symmetry energy is determined from a systematic study of the isospin dependent bulk properties of asymmetric nuclear matter using the isoscalar and the isovector components of density dependent M3Y interaction. The incompressibility $K_\\infty$ for the symmetric nuclear matter, the isospin dependent part $K_{asy}$ of the isobaric incompressibility and the slope $L$ are all in excellent agreement with the constraints recently extracted from measured isotopic de...

  3. Specifying Functional Requirements Dependency in the REWiki

    OpenAIRE

    ZHANG, ZHANG

    2013-01-01

    Most of the individual requirements cannot be treated in isolation. Requirements may affect each other in various ways. The dependency between requirements impacts a number of software development aspects and activities. How to classify and specify requirements dependency remains a classic research topic. This research aims at providing an approach of specifying functional requirements dependency. In this thesis we generalize a classification of functional requirements dependency. We also pro...

  4. Pharmacological treatments for tobacco dependence

    Directory of Open Access Journals (Sweden)

    K. O. Fagerström

    2008-12-01

    development for the treatment of tobacco dependence are cannabinoid antagonists, immunotherapy against nicotine, monoaminooxidase inhibitors, dopamine receptor D3 receptor antagonists and partial agonists, glutamatergic and GABA-ergic compounds and novel selective nicotine cholinergic receptor agonists and antagonists.

  5. Gram-scale solution-phase synthesis of selective sodium bicarbonate Co-transport Inhibitor S0859

    DEFF Research Database (Denmark)

    Larsen, Ann Møller; Krogsgaard-Larsen, Niels; Lauritzen, Gitte

    2012-01-01

    Na+-coupled HCO3- transporters (NBCs) mediate the transport of bicarbonate ions across cell membranes and are thus ubiquitous regulators of intracellular pH. NBC dysregulation is associated with a range of diseases; for instance, NBCn1 is strongly up-regulated in a model of ErbB2-dependent breast...

  6. GABA action in immature neocortical neurons directly depends on the availability of ketone bodies.

    Science.gov (United States)

    Rheims, Sylvain; Holmgren, Carl D; Chazal, Genevieve; Mulder, Jan; Harkany, Tibor; Zilberter, Tanya; Zilberter, Yuri

    2009-08-01

    In the early postnatal period, energy metabolism in the suckling rodent brain relies to a large extent on metabolic pathways alternate to glucose such as the utilization of ketone bodies (KBs). However, how KBs affect neuronal excitability is not known. Using recordings of single NMDA and GABA-activated channels in neocortical pyramidal cells we studied the effects of KBs on the resting membrane potential (E(m)) and reversal potential of GABA-induced anionic currents (E(GABA)), respectively. We show that during postnatal development (P3-P19) if neocortical brain slices are adequately supplied with KBs, E(m) and E(GABA) are both maintained at negative levels of about -83 and -80 mV, respectively. Conversely, a KB deficiency causes a significant depolarization of both E(m) (>5 mV) and E(GABA) (>15 mV). The KB-mediated shift in E(GABA) is largely determined by the interaction of the NKCC1 cotransporter and Cl(-)/HCO3 transporter(s). Therefore, by inducing a hyperpolarizing shift in E(m) and modulating GABA signaling mode, KBs can efficiently control the excitability of neonatal cortical neurons.

  7. Cytotoxicity of Carbon Nanotubes on J774 Macrophages Is a Purification-Dependent Effect

    Directory of Open Access Journals (Sweden)

    Silvia Lorena Montes-Fonseca

    2012-01-01

    Full Text Available The cytotoxicity of the carbon nanotubes (CNTs is an important factor for the manufacture of nanovaccines. The aim of this work was to evaluate the relationship of the purification method of CNTs in cellular toxicity using macrophages (MOs from the J774 cell line. Viability test was performed with MTT assays at 24 h of exposure at concentrations of 0.06, 0.6, and 6 mg/L of unpurified (UP-CNTs or purified (P-CNTs CNTs by two different methods: (1 reflux with 3M HNO3 and (2 sonication in H2SO4/HNO3. Characterization and COOH content of CNTs was performed using scanning electron microscopy, raman spectroscopy, and titration with NaHCO3. P-CNTs1 had lengths >100 μm and 2.76% COOH content, while P-CNTs2 had lengths >1 μm and 7% COOH content. This last particle showed a lower toxic effect. The results suggest that the lenght and COOH content are important factors in the toxicity of the CNTs.

  8. Exactly solvable energy-dependent potentials

    International Nuclear Information System (INIS)

    Garcia-Martinez, J.; Garcia-Ravelo, J.; Pena, J.J.; Schulze-Halberg, A.

    2009-01-01

    We introduce a method for constructing exactly-solvable Schroedinger equations with energy-dependent potentials. Our method is based on converting a general linear differential equation of second order into a Schroedinger equation with energy-dependent potential. Particular examples presented here include harmonic oscillator, Coulomb and Morse potentials with various types of energy dependence.

  9. Critical infrastructure dependencies 1-0-1

    NARCIS (Netherlands)

    Luiijf, H.A.M.; Nieuwenhuijs, A.H.; Klaver, M.H.A.

    2008-01-01

    Most of our critical infrastructures consist of complex systems-of-systems that provide services or products. The coupling mechanism between the chained systems in such complex systems of systems is dependencies. Dependencies may propagate cascading failures. Most studies on dependencies in

  10. Time-dependent Autler-Townes spectroscopy

    International Nuclear Information System (INIS)

    Qamar, Sajid; Zhu, S.-Y.; Zubairy, M Suhail

    2003-01-01

    Autler-Townes spontaneous emission spectroscopy is revisited for a time-dependent case. We report the results of spontaneous emission spectra for nonstationary scattered light signals using the definition of the time-dependent physical spectrum. This is a rare example of problems where time-dependent spectra can be calculated exactly

  11. Jealousy, Gender, Sex Roles, and Dependency.

    Science.gov (United States)

    Madden, Margaret E.; And Others

    One hundred adults ages 18 to 42 completed measures of jealousy and dependency in romantic relationships and of sex role traditionalism. Traditionalism and jealousy were correlated, as predicted, but dependency and jealousy were not. For men, but not for women, traditionalism and jealousy were positively correlated. Dependency and traditionalism…

  12. Dynamic Dependence and Diversification in Corporate Credit

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Jacobs, Kris; Jin, Xisong

    2018-01-01

    We characterize dependence in corporate credit and equity returns for 215 firms using a new class of large-scale dynamic copula models. Copula dependence and especially tail dependence are highly variable and persistent, increase significantly in the financial crisis, and have remained high since...

  13. Time-dependent Autler-Townes spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Qamar, Sajid [Institute for Quantum Studies, Department of Physics, Texas A and M University, College Station, TX 77843-4242 (United States); Zhu, S.-Y. [Institute for Quantum Studies, Department of Physics, Texas A and M University, College Station, TX 77843-4242 (United States); Zubairy, M Suhail [Institute for Quantum Studies, Department of Physics, Texas A and M University, College Station, TX 77843-4242 (United States)

    2003-04-01

    Autler-Townes spontaneous emission spectroscopy is revisited for a time-dependent case. We report the results of spontaneous emission spectra for nonstationary scattered light signals using the definition of the time-dependent physical spectrum. This is a rare example of problems where time-dependent spectra can be calculated exactly.

  14. The dynamics of cannabis use and dependence

    NARCIS (Netherlands)

    van der Pol, P.M.

    2014-01-01

    Young adults who often smoke cannabis are at higher risk of dependence, but most do not become dependent. This thesis examined the question: Which frequent cannabis users are/become/stay dependent, and seek treatment, and which do not? It was answered with a three-year prospective cohort of 600

  15. The pathological status of exercise dependence

    Science.gov (United States)

    Bamber, D.; Cockerill, I.; Carroll, D.

    2000-01-01

    Objectives—This study was concerned with the concept of exercise dependence. Levels of psychological morbidity, personality profiles, and exercise beliefs were compared among subjects screened for exercise dependence and eating disorders. Method—Adult female exercisers were allocated on the basis of questionnaire screening to one of the following groups: primary exercise dependence (n = 43); secondary exercise dependence, where there was the coincidence of exercise dependence and an eating disorder (n = 27); eating disorder (n =14); control, where there was no evidence of either exercise dependence or eating disorder (n = 110). Questionnaire assessment was undertaken of psychological morbidity, self esteem, weight and body shape dissatisfaction, personality, and exercise beliefs. Results—Aside from a higher incidence of reported menstrual abnormalities, the primary exercise dependence group was largely indistinguishable from the controls. In stark contrast, the secondary exercise dependence group reported higher levels of psychological morbidity, neuroticism, dispositional addictiveness, and impulsiveness, lower self esteem, greater concern with body shape and weight, as well as with the social, psychological, and aesthetic costs of not exercising than the controls, but differed little from the eating disorder group. Conclusions—In the absence of an eating disorder, women identified as being exercise dependent do not exhibit the sorts of personality characteristics and levels of psychological distress that warrant the construction of primary exercise dependence as a widespread pathology. Key Words: exercise dependence; eating disorders; personality; self esteem; neuroticism; psychological morbidity PMID:10786869

  16. Adult Patients' Experiences of Nursing Care Dependence.

    Science.gov (United States)

    Piredda, Michela; Matarese, Maria; Mastroianni, Chiara; D'Angelo, Daniela; Hammer, Marilyn J; De Marinis, Maria Grazia

    2015-09-01

    Care dependence can be associated with suffering and humiliation. Nurses' awareness of patients' perception of care dependence is crucial to enable them in helping the dependent persons. This study aimed to describe adult patients' experience of nursing care dependence. A metasynthesis was conducted to integrate qualitative findings from 18 studies published through December 2014 on adult patients' experiences of care dependency. Procedures included the Johanna Briggs Institute approach for data extraction, quality appraisal, and integration of findings. The experience of dependence revealed the concept of the embodied person, particularly in relation to care of the physical body. The relationship between the individual and nurses within the context of care had a major impact for dependent patients. When the care relation was perceived as positive, the experience led to the development of the person in finding new balances in life, but when it was perceived as negative, it increased patient' suffering. Care dependence is manifested mostly as bodily dependence and is consistent with its relational nature. The nurse-patient relationship is important to the dependent patients' experience. A greater understanding of patients' experiences of dependence is crucial to enable nurses in improving care and decreasing patient suffering. © 2015 Sigma Theta Tau International.

  17. Motivational and psychological correlates of bodybuilding dependence.

    Science.gov (United States)

    Emini, Neim N; Bond, Malcolm J

    2014-09-01

    Exercise may become physically and psychologically maladaptive if taken to extremes. One example is the dependence reported by some individuals who engage in weight training. The current study explored potential psychological, motivational, emotional and behavioural concomitants of bodybuilding dependence, with a particular focus on motives for weight training. Using a path analysis paradigm, putative causal models sought to explain associations among key study variables. A convenience sample of 101 men aged between 18 and 67 years was assembled from gymnasia in Adelaide, South Australia. Active weight trainers voluntarily completed a questionnaire that included measures of bodybuilding dependence (social dependency, training dependency, and mastery), anger, hostility and aggression, stress and motivations for weight training. Three motives for weight training were identified: mood control, physique anxiety and personal challenge. Of these, personal challenge and mood control were the most directly salient to dependence. Social dependency was particularly relevant to personal challenge, whereas training dependency was associated with both personal challenge and mood control. Mastery demonstrated a direct link with physique anxiety, thus reflecting a unique component of exercise dependence. While it was not possible to determine causality with the available data, the joint roles of variables that influence, or are influenced by, bodybuilding dependence are identified. RESULTS highlight unique motivations for bodybuilding and suggest that dependence could be a result of, and way of coping with, stress manifesting as aggression. A potential framework for future research is provided through the demonstration of plausible causal linkages among these variables.

  18. Holographic complexity for time-dependent backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Momeni, Davood, E-mail: davoodmomeni78@gmail.com [Eurasian International Center for Theoretical Physics and Department of General Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan); Faizal, Mir, E-mail: mirfaizalmir@googlemail.com [Irving K. Barber School of Arts and Sciences, University of British Columbia, Okanagan, 3333 University Way, Kelowna, British Columbia V1V 1V7 (Canada); Department of Physics and Astronomy, University of Lethbridge, Lethbridge, Alberta, T1K 3M4 (Canada); Bahamonde, Sebastian, E-mail: sebastian.beltran.14@ucl.ac.uk [Department of Mathematics, University College London, Gower Street, London, WC1E 6BT (United Kingdom); Myrzakulov, Ratbay [Eurasian International Center for Theoretical Physics and Department of General Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan)

    2016-11-10

    In this paper, we will analyze the holographic complexity for time-dependent asymptotically AdS geometries. We will first use a covariant zero mean curvature slicing of the time-dependent bulk geometries, and then use this co-dimension one spacelike slice of the bulk spacetime to define a co-dimension two minimal surface. The time-dependent holographic complexity will be defined using the volume enclosed by this minimal surface. This time-dependent holographic complexity will reduce to the usual holographic complexity for static geometries. We will analyze the time-dependence as a perturbation of the asymptotically AdS geometries. Thus, we will obtain time-dependent asymptotically AdS geometries, and we will calculate the holographic complexity for such time-dependent geometries.

  19. The second sodium site in the dopamine transporter controls cation permeability and is regulated by chloride

    DEFF Research Database (Denmark)

    Borre, Lars; Andreassen, Thorvald F; Shi, Lei

    2014-01-01

    The dopamine transporter (DAT) belongs to the family of neurotransmitter:sodium symporters (NSSs) and controls dopamine (DA) homeostasis by mediating Na(+)- and Cl(-)-dependent reuptake of DA. Here we used two-electrode voltage clamp measurements in Xenopus oocytes together with targeted mutagene......The dopamine transporter (DAT) belongs to the family of neurotransmitter:sodium symporters (NSSs) and controls dopamine (DA) homeostasis by mediating Na(+)- and Cl(-)-dependent reuptake of DA. Here we used two-electrode voltage clamp measurements in Xenopus oocytes together with targeted...

  20. Measuring E-cigarette dependence: Initial guidance.

    Science.gov (United States)

    Bold, Krysten W; Sussman, Steve; O'Malley, Stephanie S; Grana, Rachel; Foulds, Jonathan; Fishbein, Howard; Krishnan-Sarin, Suchitra

    2018-04-01

    E-cigarette use rates are increasing among youth and adults, despite limited knowledge about the safety, risks, and potential for this product in substituting for or reducing other tobacco use. Understanding how to characterize and assess e-cigarette dependence will be important for evaluating the public health impact of e-cigarettes and considering prevention and intervention strategies. To provide an initial review of constructs to consider when assessing e-cigarette dependence, a content expert group within the Tobacco Center for Regulatory Science (TCORS) Measurement Workgroup engaged in a review of published manuscripts and 12 tobacco dependence measures, followed by review of suggested dependence domains by a 10-person external subject-matter expert panel. The final domains selected to be considered in the development of a measure of e-cigarette dependence included: 1) Quantity and frequency of use, 2) Tolerance, 3) Perceived benefits, 4) Withdrawal symptoms, 5) Craving/urge to use, 6) Use despite harm, 7) Impaired control, 8) Automaticity, 9) Preferred over competing rewards, and 10) Sensory dependence. Similarities and differences in potential features of e-cigarette dependence compared with dependence on other tobacco products is discussed. Future work will evaluate these dependence items and constructs in a sample of e-cigarette users with a goal of developing a valid, brief, standardized measure of e-cigarette dependence. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Evolutionary ancestry and novel functions of the mammalian glucose transporter (GLUT) family.

    Science.gov (United States)

    Wilson-O'Brien, Amy L; Patron, Nicola; Rogers, Suzanne

    2010-05-21

    In general, sugar porters function by proton-coupled symport or facilitative transport modes. Symporters, coupled to electrochemical energy, transport nutrients against a substrate gradient. Facilitative carriers transport sugars along a concentration gradient, thus transport is dependent upon extracellular nutrient levels. Across bacteria, fungi, unicellular non-vertebrates and plants, proton-coupled hexose symport is a crucial process supplying energy under conditions of nutrient flux. In mammals it has been assumed that evolution of whole body regulatory mechanisms would eliminate this need. To determine whether any isoforms bearing this function might be conserved in mammals, we investigated the relationship between the transporters of animals and the proton-coupled hexose symporters found in other species. We took a comparative genomic approach and have performed the first comprehensive and statistically supported phylogenetic analysis of all mammalian glucose transporter (GLUT) isoforms. Our data reveals the mammalian GLUT proteins segregate into five distinct classes. This evolutionary ancestry gives insight to structure, function and transport mechanisms within the groups. Combined with biological assays, we present novel evidence that, in response to changing nutrient availability and environmental pH, proton-coupled, active glucose symport function is maintained in mammalian cells. The analyses show the ancestry, evolutionary conservation and biological importance of the GLUT classes. These findings significantly extend our understanding of the evolution of mammalian glucose transport systems. They also reveal that mammals may have conserved an adaptive response to nutrient demand that would have important physiological implications to cell survival and growth.

  2. 32 CFR 48.302 - Substantiating evidence regarding dependency and age of dependents.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Substantiating evidence regarding dependency and age of dependents. 48.302 Section 48.302 National Defense Department of Defense OFFICE OF THE... Designation of Beneficiaries § 48.302 Substantiating evidence regarding dependency and age of dependents. At...

  3. Telugu dependency parsing using different statistical parsers

    Directory of Open Access Journals (Sweden)

    B. Venkata Seshu Kumari

    2017-01-01

    Full Text Available In this paper we explore different statistical dependency parsers for parsing Telugu. We consider five popular dependency parsers namely, MaltParser, MSTParser, TurboParser, ZPar and Easy-First Parser. We experiment with different parser and feature settings and show the impact of different settings. We also provide a detailed analysis of the performance of all the parsers on major dependency labels. We report our results on test data of Telugu dependency treebank provided in the ICON 2010 tools contest on Indian languages dependency parsing. We obtain state-of-the art performance of 91.8% in unlabeled attachment score and 70.0% in labeled attachment score. To the best of our knowledge ours is the only work which explored all the five popular dependency parsers and compared the performance under different feature settings for Telugu.

  4. Human reliability analysis of dependent events

    International Nuclear Information System (INIS)

    Swain, A.D.; Guttmann, H.E.

    1977-01-01

    In the human reliability analysis in WASH-1400, the continuous variable of degree of interaction among human events was approximated by selecting four points on this continuum to represent the entire continuum. The four points selected were identified as zero coupling (i.e., zero dependence), complete coupling (i.e., complete dependence), and two intermediate points--loose coupling (a moderate level of dependence) and tight coupling (a high level of dependence). The paper expands the WASH-1400 treatment of common mode failure due to the interaction of human activities. Mathematical expressions for the above four levels of dependence are derived for parallel and series systems. The psychological meaning of each level of dependence is illustrated by examples, with probability tree diagrams to illustrate the use of conditional probabilities resulting from the interaction of human actions in nuclear power plant tasks

  5. Passion and dependency in online shopping activities.

    Science.gov (United States)

    Wang, Chih-Chien; Yang, Hui-Wen

    2007-04-01

    This study examines the influence of harmonious passion (HP) and obsessive passion (OP) to online shopping dependency. The results show that both HP and OP might lead to online shopping dependency and online shoppers with OP are more dependent on online shopping activities. In addition, this study also found out that HP and OP could be denoted as a sequence of different intensities of passion, where HP might be a necessity of OP.

  6. Emotional dependency: a systematic review of literature

    OpenAIRE

    Denise Catricala Bution; Amanda Muglia Wechsler

    2016-01-01

    Emotional Dependency is a disorder characterized by addictive behaviors in romantic relationships. However, there is still controversy about whether this dependency should be considered pathological, as well as its appropriate denomination and the symptoms that would define it. This paper presents a systematic evaluation of the literature on emotional dependency, reviewing all the indexed articles in Scielo, CAPES, and Scholar Google databases, published between 2000 and 2014. After careful a...

  7. Temperature dependence of nuclear surface properties

    International Nuclear Information System (INIS)

    Campi, X.; Stringari, S.

    1982-01-01

    Thermal properties of nuclear surface are investigated in a semi-infinite medium. Explicit analytical expression are given for the temperature dependence of surface thickness, surface energy and surface free energy. In this model the temperature effects depend critically on the nuclear incompressibility and on the shape of the effective mass at the surface. To illustrate the relevance of these effects we made an estimate of the temperature dependence of the fission barrier height. (orig.)

  8. Opioid dependence - management in general practice.

    Science.gov (United States)

    Frei, Matthew

    2010-08-01

    Addiction to opioids, or opioid dependence, encompasses the biopsychosocial dysfunction seen in illicit heroin injectors, as well as aberrant behaviours in patients prescribed opioids for chronic nonmalignant pain. To outline the management of opioid dependence using opioid pharmacotherapy as part of a comprehensive chronic illness management strategy. The same principles and skills general practitioners employ in chronic illness management underpin the care of patients with opioid dependence. Opioid pharmacotherapy, with the substitution medications methadone and buprenorphine, is an effective management of opioid dependence. Training and regulatory requirements for prescribing opioid pharmacotherapies vary between jurisdictions, but this treatment should be within the scope of most Australian GPs.

  9. Dependency models and probability of joint events

    International Nuclear Information System (INIS)

    Oerjasaeter, O.

    1982-08-01

    Probabilistic dependencies between components/systems are discussed with reference to a broad classification of potential failure mechanisms. Further, a generalized time-dependency model, based on conditional probabilities for estimation of the probability of joint events and event sequences is described. The applicability of this model is clarified/demonstrated by various examples. It is concluded that the described model of dependency is a useful tool for solving a variety of practical problems concerning the probability of joint events and event sequences where common cause and time-dependent failure mechanisms are involved. (Auth.)

  10. Nonlinear system theory: another look at dependence.

    Science.gov (United States)

    Wu, Wei Biao

    2005-10-04

    Based on the nonlinear system theory, we introduce previously undescribed dependence measures for stationary causal processes. Our physical and predictive dependence measures quantify the degree of dependence of outputs on inputs in physical systems. The proposed dependence measures provide a natural framework for a limit theory for stationary processes. In particular, under conditions with quite simple forms, we present limit theorems for partial sums, empirical processes, and kernel density estimates. The conditions are mild and easily verifiable because they are directly related to the data-generating mechanisms.

  11. Polysomnographic Sleep Dysregulation in Cocaine Dependence

    Directory of Open Access Journals (Sweden)

    Edwin M. Valladares

    2007-01-01

    Full Text Available Insomnia and sleep disturbance are associated with declines in health functioning, alongwith increases in mortality risk. Given the prominence of reported sleep disturbance incocaine-dependent subjects and persistence into recovery, understanding the natureand severity of these disturbances in this population may help to identify relevantpathways that contribute to the increased mortality in cocaine dependence. Polysomnography provides a means of objectively characterizing sleep and, in turn, sleep disturbances. Few studies have used polysomnography to evaluate sleep incocaine-dependent persons, yet these studies have the potential to advance treatmentsthat will ultimately reduce morbidity in cocaine-dependent subjects.

  12. The dynamics of cannabis use and dependence

    OpenAIRE

    van der Pol, P.M.

    2014-01-01

    Young adults who often smoke cannabis are at higher risk of dependence, but most do not become dependent. This thesis examined the question: Which frequent cannabis users are/become/stay dependent, and seek treatment, and which do not? It was answered with a three-year prospective cohort of 600 young adults (18-30 years) who used cannabis frequently (≥3 days weekly for >1 year), distinguishing users with and without dependence; comparisons with non-users and patients in treatment; and ‘natura...

  13. Time-dependent behavior of concrete

    International Nuclear Information System (INIS)

    Pfeiffer, P.A.; Tanabe, Tada-aki

    1992-01-01

    This paper is a condensed version of the material presented at the International Workshop on Finite Element Analysis of Reinforced Concrete, Session 4 -- Time Dependent Behavior, held at Columbia University, New York on June 3--6, 1991. Dr. P.A. Pfeiffer presented recent developments in time-dependent behavior of concrete and Professor T. Tanabe presented a review of research in Japan on time-dependent behavior of concrete. The paper discusses the recent research of time-dependent behavior of concrete in the past few years. 6 refs

  14. Spin dependent spectroscopy of heavy quarkonium

    International Nuclear Information System (INIS)

    Gupta, Pramila; Mehrotra, I.

    2011-01-01

    In the present work mass spectroscopy of charmonium and bottonium systems has been studied using energy dependent quark interquark potential in the framework of non-relativistic Schroedinger wave equation. Energy dependence gives rise to nonlocality in the potential. These authors have used the interquark potential to be of the form of harmonic oscillator with a small linear energy dependent perturbation. Their main conclusion is that energy dependence can account for saturation of the energy levels at higher excitation energies, a feature that is observed experimentally

  15. Socio-emotional factors in alcohol dependence

    OpenAIRE

    Deyashini Lahiri Tikka; Daya Ram; Indu Dubey; Sai Krishna Tikka

    2014-01-01

    Background: Alcohol-dependent patients are traditionally believed to have insecure attachment styles, higher anger expression, and lower self-esteem. There is a need to study them together. Aim: To understand the relationships amongst various of the socio-emotional factors. Materials and Methods: Forty male patients with Alcohol dependence syndrome and 40 matched healthy controls (General Health Questionnaire-12 score

  16. Questions and dependency in intuitionistic logic

    NARCIS (Netherlands)

    Ciardelli, Ivano; Iemhoff, Rosalie; Yang, Fan

    2017-01-01

    In recent years, the logic of questions and dependencies has been investigated in the closely related frameworks of inquisitive logic and dependence logic. These investigations have assumed classical logic as the background logic of statements, and added formulas expressing questions and

  17. Dependent Children and Suicide of Married Parents.

    Science.gov (United States)

    Kozak, Conrad M.; Gibbs, James O.

    1979-01-01

    Single suicides and married suicides with dependent children were compared to similar groups in the general population. Married people with dependent children experienced the lowest average suicide rate, but had a larger mean number of children than the population as a whole. (Author)

  18. Two Generations of Path Dependence in Economics?

    DEFF Research Database (Denmark)

    Madsen, Mogens Ove

    2010-01-01

    Even if there is no fully articulated and generally accepted theory of Path Dependence it has eagerly been taken up across a wide range of social sciences – primarily coming from economics. Path Dependence is most of all a metaphor that offers reason to believe, that some political, social...

  19. Temperature dependence of elastic properties of paratellurite

    International Nuclear Information System (INIS)

    Silvestrova, I.M.; Pisarevskii, Y.V.; Senyushenkov, P.A.; Krupny, A.I.

    1987-01-01

    New data are presented on the temperature dependence of the elastic wave velocities, elastic stiffness constants, and thermal expansion of paratellurite. It is shown that the external pressure appreciably influences the elastic properties of TeO 2 , especially the temperature dependence of the elastic modulus connected with the crystal soft mode. (author)

  20. Resource Abundance and Resource Dependence in China

    NARCIS (Netherlands)

    Ji, K.; Magnus, J.R.; Wang, W.

    2010-01-01

    This paper reconsiders the ‘curse of resources’ hypothesis for the case of China, and distinguishes between resource abundance, resource rents, and resource dependence. Resource abundance and resource rents are shown to be approximately equivalent, and their association with resource dependence

  1. Chemical Dependency Regional Needs Assessment: Northeastern Minnesota.

    Science.gov (United States)

    Stone, Marylee

    The Minnesota Model of Chemical Dependency Treatment, which evolved from a combination of the grassroots Alcoholics Anonymous movement and the State Mental Health Services in the 1960s has made Minnesota an international leader in chemical dependency treatment efforts. Northeastern Minnesota has shared this reputation with the state. In spite of…

  2. Outsourcing relationships: Changes in power and dependency

    DEFF Research Database (Denmark)

    Hansen, Zaza Nadja Lee; Rasmussen, Lauge Baungaard

    2013-01-01

    Recent research has shown that it is important for companies to correctly reflect the power and (inter)dependency to vendors so that an appropriate and aligned relationship can be created. Power and dependency, however, can change over time, which means that the vendor strategy necessary for the ...

  3. Dependent failure analysis of NPP data bases

    International Nuclear Information System (INIS)

    Cooper, S.E.; Lofgren, E.V.; Samanta, P.K.; Wong Seemeng

    1993-01-01

    A technical approach for analyzing plant-specific data bases for vulnerabilities to dependent failures has been developed and applied. Since the focus of this work is to aid in the formulation of defenses to dependent failures, rather than to quantify dependent failure probabilities, the approach of this analysis is critically different. For instance, the determination of component failure dependencies has been based upon identical failure mechanisms related to component piecepart failures, rather than failure modes. Also, component failures involving all types of component function loss (e.g., catastrophic, degraded, incipient) are equally important to the predictive purposes of dependent failure defense development. Consequently, dependent component failures are identified with a different dependent failure definition which uses a component failure mechanism categorization scheme in this study. In this context, clusters of component failures which satisfy the revised dependent failure definition are termed common failure mechanism (CFM) events. Motor-operated valves (MOVs) in two nuclear power plant data bases have been analyzed with this approach. The analysis results include seven different failure mechanism categories; identified potential CFM events; an assessment of the risk-significance of the potential CFM events using existing probabilistic risk assessments (PRAs); and postulated defenses to the identified potential CFM events. (orig.)

  4. Dependability Evaluation of Advanced Diverse Protection System

    International Nuclear Information System (INIS)

    Oh, Yang Gyun; Lee, Yoon Hee; Sohn, Se Do; Baek, Seung Min; Lee, Sang Jeong

    2014-01-01

    For the mitigation of anticipated transients without scram (ATWS) as well as common cause failure (CCF) within the plant protection system (PPS) and the emergency safety feature . component control system (ESF-CCS), the diverse protection system (DPS) has been designed by KEPCO Engineering and Construction Company. Recently KEPCO E and C has developed the advanced diverse protection system (ADPS), which has four redundant channels, in an attempt to enhance a fault-tolerant capability of the system. For the evaluation of overall system improvement effects of the ADPS compared with the DPS, the dependability evaluation results are described herein. For all dependability attributes, this paper suggests a practical dependability evaluation method which uses quantitative dependability scores and indices. An overall dependability evaluation index (DEI) for the ADPS is evaluated with the average value of reliability/ security/maintainability/safety indices (i.e., RID, SID, MID, and SID') for dependability. The evaluation results show that the DEI value of ADPS can be improved by approximately 23% compared with that of the DPS, thanks to its fault-tolerant system architecture, software design changes, and external interface design features. Several suggestions have been made, in this paper, of an overall quantitative dependability evaluation method for the nuclear instrumentation and control (I and C) systems including the DPS and ADPS, and the usefulness of dependability evaluation on nuclear I and C systems has been confirmed

  5. Escherichia coli survival in waters: Temperature dependence

    Science.gov (United States)

    Knowing the survival rates of water-borne Escherichia coli is important in evaluating microbial contamination and making appropriate management decisions. E. coli survival rates are dependent on temperature, a dependency that is routinely expressed using an analogue of the Q10 mo...

  6. Stress Testing with Student's t Dependence

    NARCIS (Netherlands)

    H.J.W.G. Kole (Erik); C.G. Koedijk (Kees); M.J.C.M. Verbeek (Marno)

    2003-01-01

    textabstractIn this study we propose the use of the Student's t dependence function to model dependence between asset returns when conducting stress tests. To properly include stress testing in a risk management system, it is important to have accurate information about the (joint) probabilities of

  7. Empirical Evaluation of Directional-Dependence Tests

    Science.gov (United States)

    Thoemmes, Felix

    2015-01-01

    Testing of directional dependence is a method to infer causal direction that recently has attracted some attention. Previous examples by e.g. von Eye and DeShon (2012a) and extensive simulation studies by Pornprasertmanit and Little (2012) have demonstrated that under specific assumptions, directional-dependence tests can recover the true causal…

  8. Pentazocine dependence among sickle cell disease patients ...

    African Journals Online (AJOL)

    Introduction: Sickle cell disease is a chronic disease. Severe bone pain is commonly the hallmark of clinical features. This commonly necessitates the use of analgesics especially Opioids which unfortunately have a high potential to produce dependence. The complications of dependence in patients on any psychoactive ...

  9. Dependency safety for Java - implementing failboxes

    NARCIS (Netherlands)

    Bosnacki, D.; van den Brand, M.G.J.; Denissen, P.E.J.G.; Huizing, C.; Jacobs, B.; Kuiper, R.; Wijs, A.J.; Wiłkowski, M.; Zhang, D.

    2016-01-01

    Exception mechanisms help to ensure that a program satisfies the important robustness criterion of dependency safety: if an operation fails, no code that depends on the operation's successful completion is executed anymore nor will wait for the completion. However, the exception handling mechanisms

  10. 5 CFR 843.405 - Dependency.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Dependency. 843.405 Section 843.405 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Child Annuities § 843.405 Dependency. To be...

  11. Assessment of Dependency, Agreeableness, and Their Relationship

    Science.gov (United States)

    Lowe, Jennifer Ruth; Edmundson, Maryanne; Widiger, Thomas A.

    2009-01-01

    Agreeableness is central to the 5-factor model conceptualization of dependency. However, 4 meta-analyses of the relationship of agreeableness with dependency have failed to identify a consistent relationship. It was the hypothesis of the current study that these findings might be due in part to an emphasis on the assessment of adaptive, rather…

  12. Determining Directional Dependency in Causal Associations

    Science.gov (United States)

    Pornprasertmanit, Sunthud; Little, Todd D.

    2012-01-01

    Directional dependency is a method to determine the likely causal direction of effect between two variables. This article aims to critique and improve upon the use of directional dependency as a technique to infer causal associations. We comment on several issues raised by von Eye and DeShon (2012), including: encouraging the use of the signs of…

  13. Exactly solvable position dependent mass schroedinger equation

    International Nuclear Information System (INIS)

    Koc, R.; Tuetuencueler, H.; Koercuek, E.

    2002-01-01

    Exact solution of the Schrodinger equation with a variable mass is presented. We have derived general expressions for the eigenstates and eigenvalues of the position dependent mass systems. We provide supersymmetric and Lie algebraic methods to discuss the position dependent mass systems

  14. Chemical dependency and adolescent self-esteem.

    Science.gov (United States)

    Wasson, D; Anderson, M A

    1995-08-01

    The purpose of this descriptive study is to determine whether self-esteem differs between chemically dependent adolescents and adolescents from the general high school population. The Self-Esteem Inventory (Coopersmith, 1987) was completed by 119 adolescents (31 inpatient, 31 aftercare, and 57 general high school students) aged 13 to 18. Findings suggest that inpatient, chemically dependent adolescents have lower self-esteem than the other two groups. For the chemically dependent adolescent, nursing case management with communication among and between health care providers, school professionals, and family may facilitate successful, long-term recovery. For adolescents at risk for development of chemical dependence, nursing health promotion behaviors, such as early assessment and implementation of self-esteem-building activities, may assist in prevention of chemical dependency.

  15. Isospin dependent properties of asymmetric nuclear matter

    Science.gov (United States)

    Chowdhury, P. Roy; Basu, D. N.; Samanta, C.

    2009-07-01

    The density dependence of nuclear symmetry energy is determined from a systematic study of the isospin dependent bulk properties of asymmetric nuclear matter using the isoscalar and isovector components of the density dependent M3Y interaction. The incompressibility K∞ for the symmetric nuclear matter, the isospin dependent part Kasy of the isobaric incompressibility, and the slope L are all in excellent agreement with the constraints recently extracted from measured isotopic dependence of the giant monopole resonances in even-A Sn isotopes, from the neutron skin thickness of nuclei, and from analyses of experimental data on isospin diffusion and isotopic scaling in intermediate energy heavy-ion collisions. This work provides a fundamental basis for the understanding of nuclear matter under extreme conditions and validates the important empirical constraints obtained from recent experimental data.

  16. Infliximab dependency in children with Crohn's disease

    DEFF Research Database (Denmark)

    Duricova, D; Pedersen, N; Lenicek, M

    2009-01-01

    BACKGROUND: Recently, infliximab dependency has been described. AIM: To assess frequency of ID in 82 consecutive Crohn's disease children treated with infliximab 2000-2006 and to describe clinical and genetic predictors of long-term infliximab response. METHODS: A phenotype model of infliximab...... dependency was used to assess treatment response: 'immediate outcome' (30 days after infliximab start)--complete/partial/no response. 'Long-term outcome': (i) prolonged response: maintenance of complete/partial response; (ii) infliximab dependency: relapse .../partial response. In long-term outcome, 22% maintained prolonged response, 12% had no response, while 66% became infliximab dependent. Perianal disease and no previous surgery were associated with infliximab dependency (OR 5.34, 95% CI: 1.24-22.55; OR 6.7, 95% CI: 1.67-26.61). No association was found with studied...

  17. Extracellular acidosis and very low [Na+ ] inhibit NBCn1- and NHE1-mediated net acid extrusion from mouse vascular smooth muscle cells.

    Science.gov (United States)

    Bonde, L; Boedtkjer, E

    2017-10-01

    The electroneutral Na + , HCO3- cotransporter NBCn1 and Na + /H + exchanger NHE1 regulate acid-base balance in vascular smooth muscle cells (VSMCs) and modify artery function and structure. Pathological conditions - notably ischaemia - can dramatically perturb intracellular (i) and extracellular (o) pH and [Na + ]. We examined effects of low [Na + ] o and pH o on NBCn1 and NHE1 activity in VSMCs of small arteries. We measured pH i by 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein-based fluorescence microscopy of mouse mesenteric arteries and induced intracellular acidification by NH4+ prepulse technique. NBCn1 activity - defined as Na + -dependent, amiloride-insensitive net base uptake with CO 2 /HCO3- present - was inhibited equally when pH o decreased from 7.4 (22 mm HCO3-/5% CO 2 ) by metabolic (pH o 7.1/11 mm HCO3-: 22 ± 8%; pH o 6.8/5.5 mm HCO3-: 61 ± 7%) or respiratory (pH o 7.1/10% CO 2 : 35 ± 11%; pH o 6.8/20% CO 2 : 56 ± 7%) acidosis. Extracellular acidosis more prominently inhibited NHE1 activity - defined as Na + -dependent net acid extrusion without CO 2 /HCO3- present - at both pH o 7.1 (45 ± 9%) and 6.8 (85 ± 5%). Independently of pH o , lowering [Na + ] o from 140 to 70 mm reduced NBCn1 and NHE1 activity respiratory (ΔpH i /ΔpH o  = 71 ± 4%) than metabolic (ΔpH i /ΔpH o  = 30 ± 7%) acidosis. Extracellular acidification inhibits NBCn1 and NHE1 activity in VSMCs. NBCn1 is equivalently inhibited when pCO 2 is raised or [HCO3-] o decreased. Lowering [Na + ] o inhibits NBCn1 and NHE1 markedly only below the typical physiological and pathophysiological range. We propose that inhibition of Na + -dependent net acid extrusion at low pH o protects against cellular Na + overload at the cost of intracellular acidification. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  18. Measurement of exercise dependence in bodybuilders.

    Science.gov (United States)

    Smith, D K; Hale, B D; Collins, D

    1998-03-01

    The purpose of this study was to explore exercise dependence in bodybuilders, and undertake preliminary validation of a measurement instrument. A comparative analysis of self-report indices between groups. Forty-seven bodybuilders, 31 individuals who weight trained for general fitness purposes and 24 weightlifters participated in the study. Each subject completed the following: demographic information, bodybuilding-specific versions of the social identity and exclusivity scales of the Athletic Identity Measurement Scale, the physical strength and body attractiveness subscales of the Physical Self-Perception Profile, a short form of the Marlowe-Crowne Social Desirability Scale, and a 9-item Bodybuilding Dependence Scale. Factor analysis on the BDS revealed 3 subscales (social dependency, training dependency and mastery) which accounted for 68.4% of the variance. Internal consistency was satisfactory for each subscale (Chronbach's alpha = 0.76, 0.75 and 0.78 respectively). The BDS social dependency and PSPP body attractiveness scores of the bodybuilders were higher than those of the weightlifters, whose scores were higher than those of the fitness trainers. The bodybuilders scored higher on both AIMS subscales than the other groups. The bodybuilders and weightlifters scored higher on PSPP physical strength than the fitness trainers. BDS social dependency correlated with both AIMS and both PSPP subscales, and BDS training dependency correlated with AIMS exclusivity. All three BDS subscales correlated with training frequency. Discriminant analysis found the combination of AIMS social identity, BDS social dependency and years training experience enabled correct classification of 92% of the respondents. These results support the construct and concurrent validity of the BDS social dependency subscale, but do not wholly support the validity of the other two subscales.

  19. Competing risks and time-dependent covariates

    DEFF Research Database (Denmark)

    Cortese, Giuliana; Andersen, Per K

    2010-01-01

    Time-dependent covariates are frequently encountered in regression analysis for event history data and competing risks. They are often essential predictors, which cannot be substituted by time-fixed covariates. This study briefly recalls the different types of time-dependent covariates......, as classified by Kalbfleisch and Prentice [The Statistical Analysis of Failure Time Data, Wiley, New York, 2002] with the intent of clarifying their role and emphasizing the limitations in standard survival models and in the competing risks setting. If random (internal) time-dependent covariates...

  20. US oil dependency and energy security

    International Nuclear Information System (INIS)

    Noel, P.

    2002-01-01

    The three papers of this document were written in the framework of a seminar organized the 30 may 2002 by the IFRI in the framework of its program Energy and Climatic Change. The first presentation deals with the american oil policy since 1980 (relation between the oil dependence and the energy security, the Reagan oil policy, the new oil policy facing the increase of the dependence). The second one deals with the US energy security (oil security, domestic energy security, policy implications). The last presentation is devoted to the US oil dependence in a global context and the problems and policies of international energy security. (A.L.B.)

  1. Predictors of mortality in insulin dependent diabetes

    DEFF Research Database (Denmark)

    Rossing, P; Hougaard, P; Borch-Johnsen, K

    1996-01-01

    OBJECTIVE: To evaluate the prognostic significance of microalbuminuria and overt diabetic nephropathy and other putative risk factors for cardiovascular and all cause mortality in insulin dependent diabetes. DESIGN: Ten year observational follow up study. SETTING: Outpatient diabetic clinic...... in a tertiary referral centre. SUBJECTS: All 939 adults with insulin dependent diabetes (duration of diabetes five years or more) attending the clinic in 1984; 593 had normal urinary albumin excretion ( or = 300 mg...... and other potentially modifiable risk factors such as hypertension, smoking, poor glycaemic control, and social class predict increased mortality in insulin dependent diabetes. Microalbuminuria by itself confers only a small increase in mortality. The prognosis of patients with overt diabetic nephropathy...

  2. Robust classification using mixtures of dependency networks

    DEFF Research Database (Denmark)

    Gámez, José A.; Mateo, Juan L.; Nielsen, Thomas Dyhre

    2008-01-01

    Dependency networks have previously been proposed as alternatives to e.g. Bayesian networks by supporting fast algorithms for automatic learning. Recently dependency networks have also been proposed as classification models, but as with e.g. general probabilistic inference, the reported speed......-ups are often obtained at the expense of accuracy. In this paper we try to address this issue through the use of mixtures of dependency networks. To reduce learning time and improve robustness when dealing with data sparse classes, we outline methods for reusing calculations across mixture components. Finally...

  3. Phase-dependent noise in Josephson junctions

    Science.gov (United States)

    Sheldon, Forrest; Peotta, Sebastiano; Di Ventra, Massimiliano

    2018-03-01

    In addition to the usual superconducting current, Josephson junctions (JJs) support a phase-dependent conductance related to the retardation effect of tunneling quasi-particles. This introduces a dissipative current with a memory-resistive (memristive) character that should also affect the current noise. By means of the microscopic theory of tunnel junctions we compute the complete current autocorrelation function of a Josephson tunnel junction and show that this memristive component gives rise to both a previously noted phase-dependent thermal noise, and an undescribed non-stationary, phase-dependent dynamic noise. As experiments are approaching ranges in which these effects may be observed, we examine the form and magnitude of these processes. Their phase dependence can be realized experimentally as a hysteresis effect and may be used to probe defects present in JJ based qubits and in other superconducting electronics applications.

  4. Emotional awareness in substance-dependent patients.

    Science.gov (United States)

    Carton, Solange; Bayard, Sophie; Paget, Virginie; Jouanne, Céline; Varescon, Isabelle; Edel, Yves; Detilleux, Michel

    2010-06-01

    We explored emotional awareness in substance-dependent patients and its relationships to self-reported alexithymia. Sixty-four outpatients with drug dependence or alcohol dependence were evaluated before the beginning of treatment with the Hamilton Depressive Scale and the Covi Anxiety Scale, and they completed the Toronto Alexithymia Scale (TAS-20) and the Levels of Emotional Awareness Scale (LEAS). Subjects exhibited low levels of emotional awareness and TAS-20 scores were high. Both measures were not related to depressive and anxious symptomatology. This research is the first to provide LEAS results with substance-dependent patients and highlights their deficits in emotions' differentiation and complexity. The lack of a relationship between LEAS and TAS-20 is discussed from the methodological and theoretical points of view. (c) 2010 Wiley Periodicals, Inc.

  5. Sequential dependencies in magnitude scaling of loudness

    DEFF Research Database (Denmark)

    Joshi, Suyash Narendra; Jesteadt, Walt

    2013-01-01

    Ten normally hearing listeners used a programmable sone-potentiometer knob to adjust the level of a 1000-Hz sinusoid to match the loudness of numbers presented to them in a magnitude production task. Three different power-law exponents (0.15, 0.30, and 0.60) and a log-law with equal steps in d......B were used to program the sone-potentiometer. The knob settings systematically influenced the form of the loudness function. Time series analysis was used to assess the sequential dependencies in the data, which increased with increasing exponent and were greatest for the log-law. It would be possible......, therefore, to choose knob properties that minimized these dependencies. When the sequential dependencies were removed from the data, the slope of the loudness functions did not change, but the variability decreased. Sequential dependencies were only present when the level of the tone on the previous trial...

  6. Free Beauty, Dependent Beauty, and Art.

    Science.gov (United States)

    Stecker, Robert

    1987-01-01

    Explains the difference between free and dependent beauty. States that these distinctions, formed by Immanuel Kant, have important implications for aesthetic education. Concludes with a defense of Kant's aesthetics. (JDH)

  7. Time-dependent, Bianchi II, rotating universe

    International Nuclear Information System (INIS)

    Reboucas, M.J.

    1981-01-01

    An exact cosmological solution of Einstein's equations which has time-dependent rotation is presented. The t-constant sections are of Bianchi type II. The source of this geometry is a fluid which has not been thermalized. (Author) [pt

  8. Can You Depend Totally on Computers?

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 3; Issue 2. Can You Depend Totally on Computers? Computer Security, Availability and Correctness. H N Mahabala. General Article Volume 3 Issue 2 February 1998 pp 35-44 ...

  9. Multilevel Cross-Dependent Binary Longitudinal Data

    KAUST Repository

    Serban, Nicoleta; Staicu, Ana-Maria; Carroll, Raymond J.

    2013-01-01

    processes describing the within- and between-variability, and describing the cross-dependence of the repeated longitudinal measurements. We estimate the model components without employing mixed-effects modeling but assuming an approximation to the logistic

  10. Topic 5: Time-Dependent Behavior

    International Nuclear Information System (INIS)

    Pfeiffer, P.A.; Tanabe, Tada-aki

    1991-01-01

    This chapter is a report of the material presented at the International Workshop on Finite Element Analysis of Reinforced Concrete, Session 4 -- Time Dependent Behavior, held at Columbia University, New York on June 3--6, 1991. Dr. P.A. Pfeiffer presented recent developments in time-dependent behavior of concrete and Professor T. Tanabe presented a review of research in Japan on time-dependent behavior of concrete. The chapter discusses the recent research of time-dependent behavior of concrete in the past few years in both the USA-European and Japanese communities. The author appreciates the valuable information provided by Zdenek P. Bazant in preparing the USA-European Research section

  11. Indoor Tanning Dependence in Young Adult Women.

    Science.gov (United States)

    Mays, Darren; Atkins, Michael B; Ahn, Jaeil; Tercyak, Kenneth P

    2017-11-01

    Background: There is mounting evidence that young people can develop a dependence on indoor tanning, but research on factors associated with indoor tanning dependence remains limited. Methods: This cross-sectional study investigated factors associated with indoor tanning dependence in a community sample of 389 non-Hispanic white young adult women ages 18 to 30 who had indoor tanned ≥1 time in the past year. Participants completed measures of indoor tanning dependence, including the modified CAGE and modified Diagnostic and Statistical Manual for Mental Disorders-IV psychiatric screening assessments, indoor tanning behavior and beliefs, and behavioral and psychiatric comorbidity. Results: Overall, 22.6% of the sample screened positive for indoor tanning dependence. In multivariable analyses, indoor tanning dependence was associated with younger age of indoor tanning initiation [adjusted odds ratio (aOR) = 0.79; P = 0.017], indoor tanning ≥20 times in the past year (aOR = 3.03; P = 0.015), stronger beliefs about the benefits of tanning (aOR = 2.15; P = 0.004), greater perceived susceptibility to indoor tanning risks (aOR = 2.72; P tanning dependence among young, non-Hispanic white women is associated with behaviors that increase the risk of skin cancer, beliefs favoring the perceived benefits of tanning, and comorbid risks such as stronger beliefs about physical appearance and depressed mood. Impact: Comprehensive skin cancer prevention efforts should address indoor tanning dependence among young women and its leading risk factors. Cancer Epidemiol Biomarkers Prev; 26(11); 1636-43. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. Livelihood strategies, environmental dependency and rural poverty

    DEFF Research Database (Denmark)

    Walelign, Solomon Zena

    2016-01-01

    This article attempts to explore the nexus between rural households’ environmental dependency, poverty and livelihood strategies. Households’ income from each livelihood activities formed the basis for categorizing households according to livelihood strategies. The principal component analysis...... of livelihood choice were analyzed using multinomial logit model. The results indicate the existence of marked differences in environmental dependency, rural poverty and asset endowments across the livelihood groups. Household’s total saving, access to credit, production implements, business cost, exposure...

  13. Strategies for state-dependent quantum deleting

    International Nuclear Information System (INIS)

    Song Wei; Yang Ming; Cao Zhuoliang

    2004-01-01

    A quantum state-dependent quantum deleting machine is constructed. We obtain a upper bound of the global fidelity on N-to-M quantum deleting from a set of K non-orthogonal states. Quantum networks are constructed for the above state-dependent quantum deleting machine when K=2. Our deleting protocol only involves a unitary interaction among the initial copies, with no ancilla. We also present some analogies between quantum cloning and deleting

  14. Creating opioid dependence in the emergency department.

    Science.gov (United States)

    Upadhye, Suneel

    2018-01-01

    Clinical question What is the risk of creating opioid dependence from an ED opioid prescription? Article chosen Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017;376:663-73, doi:10.1056/NEJMsa1610524. This study examined the risk of creating long-term opioid dependence from a prescription written in an opioid-naive patient in the ED.

  15. [From dependency to autonomy, a geriatric pathway].

    Science.gov (United States)

    Iglesias, Antoine; Da Costa Ribeiro, Florence; Pedra, Maryse; Chassaigne, Marie-Christine; Berbon, Caroline

    Preventing dependency is essential in our ageing society. One of its components is the avoidable dependency which develops during a period of hospitalisation. Caregivers play an important role in helping the elderly person regain their autonomy. Various actions have been undertaken on this theme within the gerontology unit of Toulouse university hospital, including the creation of a multi-disciplinary group of experts among the caregivers working in the unit. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Evaluation of temperature dependent neutron resonance integrals

    International Nuclear Information System (INIS)

    Menon, S.V.G.; Sahni, D.C.

    1975-01-01

    The Fourier transform method is extended for evaluating temperature dependent resonance integrals and Doppler coefficients. With the temperature dependent cross-sections, the slowing-down equation is transformed into a Fredholm integral equation of second kind. A method of solution is presented using the familiar Gauss-Hermite quadrature formulae. As a byproduct of the above technique, a fast and accurate method for computing the resonance integral J-function is given. (orig.) [de

  17. The cyanobacterial bicarbonate transporter BicA: its physiological role and the implications of structural similarities with human SLC26 transporters.

    Science.gov (United States)

    Price, G Dean; Howitt, Susan M

    2011-04-01

    The cyanobacterial Na+-dependent HCO3- transporter BicA is a member of the ubiquitous and important SulP/SLC26 family of anion transporters found in eukaryotes and prokaryotes. BicA is an important component of the cyanobacterial CO2 concentrating mechanism, an adaptation that contributes to cyanobacteria being able to achieve an estimated 25% of global primary productivity, largely in the oceans. The human SLC26 members are involved in a range of key cellular functions involving a diverse range of anion transport activities including Cl-/HCO3-, I-/HCO3-, and SO42-/HCO3- exchange; mutations in SLC26 members are known to be associated with debilitating diseases such as Pendred syndrome, chondrodysplasias, and congenital chloride diarrhoea. We have recently experimentally determined the membrane topology of BicA using the phoA-lacZ reporter system and here consider some of the extrapolated implications for topology of the human SLC26 family and the Sultr plant sulphate transporters.

  18. Bicarbonate diffusion through mucus.

    Science.gov (United States)

    Livingston, E H; Miller, J; Engel, E

    1995-09-01

    The mucus layer overlying duodenal epithelium maintains a pH gradient against high luminal acid concentrations. Despite these adverse conditions, epithelial surface pH remains close to neutrality. The exact nature of the gradient-forming barrier remains unknown. The barrier consists of mucus into which HCO3- is secreted. Quantification of the ability of HCO3- to establish and maintain the gradient depends on accurate measurement of this ion's diffusion coefficient through mucus. We describe new experimental and mathematical methods for diffusion measurement and report diffusion coefficients for HCO3- diffusion through saline, 5% mucin solutions, and rat duodenal mucus. The diffusion coefficients were 20.2 +/- 0.10, 3.02 +/- 0.31, and 1.81 +/- 0.12 x 10(-6) cm2/s, respectively. Modeling of the mucobicarbonate layer with this latter value suggests that for conditions of high luminal acid strength the neutralization of acid by HCO3- occurs just above the epithelial surface. Under these conditions the model predicts that fluid convection toward the lumen could be important in maintaining the pH gradient. In support of this hypothesis we were able to demonstrate a net luminal fluid flux of 5 microliters.min-1.cm-2 after perfusion of 0.15 N HCl in the rat duodenum.

  19. Caregiver Burden in Alcohol Dependence Syndrome

    Directory of Open Access Journals (Sweden)

    Ramanujam Vaishnavi

    2017-01-01

    Full Text Available Background. Alcoholism is a major threat to the individual as well as the society and the maximum burden of the illness is borne by the family. Aim. The study is aimed at assessing the pattern of burden on the caregivers of alcohol dependent patients and at assessing the relationship between the severity of dependence and the burden on caregivers. Settings and Design. Cross-sectional descriptive study conducted in the Department of Psychiatry, Sri Ramachandra Medical College and Research Institute. Materials and Methods. A cross-sectional assessment was done in 200 patients with alcohol dependence and their caregivers. The severity of dependence and the pattern of burden on caregivers were assessed. Statistical Analysis. The data thus collected was analyzed using SPSS version 20. Results. The study demonstrates that caregivers of alcohol dependent patients reported significant objective burden and subjective burden. Furthermore, the severity of alcohol dependence and the domains of burden such as financial burden, disruption of family interaction, and disruption of family routine activities were positively correlated with high level of significance. Conclusion. The current study has illustrated that all the caregivers experienced significant amount of burden which has to be addressed for better treatment outcome of the patients.

  20. Liquid-filled ionization chamber temperature dependence

    Energy Technology Data Exchange (ETDEWEB)

    Franco, L. [Dpto. de Fisica de Particulas, Facultade de Fisica, Universidade de Santiago, Campus Sur S/N, 15782 Santiago de Compostela (Spain)]. E-mail: luciaff@usc.es; Gomez, F. [Dpto. de Fisica de Particulas, Facultade de Fisica, Universidade de Santiago, Campus Sur S/N, 15782 Santiago de Compostela (Spain); Iglesias, A. [Dpto. de Fisica de Particulas, Facultade de Fisica, Universidade de Santiago, Campus Sur S/N, 15782 Santiago de Compostela (Spain); Pardo, J. [Dpto. de Fisica de Particulas, Facultade de Fisica, Universidade de Santiago, Campus Sur S/N, 15782 Santiago de Compostela (Spain); Pazos, A. [Dpto. de Fisica de Particulas, Facultade de Fisica, Universidade de Santiago, Campus Sur S/N, 15782 Santiago de Compostela (Spain); Pena, J. [Dpto. de Fisica de Particulas, Facultade de Fisica, Universidade de Santiago, Campus Sur S/N, 15782 Santiago de Compostela (Spain); Zapata, M. [Dpto. de Fisica de Particulas, Facultade de Fisica, Universidade de Santiago, Campus Sur S/N, 15782 Santiago de Compostela (Spain)

    2006-05-10

    Temperature and pressure corrections of the read-out signal of ionization chambers have a crucial importance in order to perform high-precision absolute dose measurements. In the present work the temperature and pressure dependences of a sealed liquid isooctane filled ionization chamber (previously developed by the authors) for radiotherapy applications have been studied. We have analyzed the thermal response of the liquid ionization chamber in a {approx}20 deg. C interval around room temperature. The temperature dependence of the signal can be considered linear, with a slope that depends on the chamber collection electric field. For example, a relative signal slope of 0.27x10{sup -2}K{sup -1} for an operation electric field of 1.67x10{sup 6}Vm{sup -1} has been measured in our detector. On the other hand, ambient pressure dependence has been found negligible, as expected for liquid-filled chambers. The thermal dependence of the liquid ionization chamber signal can be parametrized within the Onsager theory on initial recombination. Considering that changes with temperature of the detector response are due to variations in the free ion yield, a parametrization of this dependence has been obtained. There is a good agreement between the experimental data and the theoretical model from the Onsager framework.

  1. Affective Dependence and Aggression: An Exploratory Study

    Directory of Open Access Journals (Sweden)

    Filippo Petruccelli

    2014-01-01

    Full Text Available Introduction. Emotionally dependent subjects may engage in controlling, restrictive, and aggressive behaviours, which limit their partner’s autonomy. The underlying causes of such behaviours are not solely based on levels of aggression, but act as a mean of maintaining the subject’s own sense of self-worth, identity, and general functioning. Objective. The aim of the paper is to explore the correlation between affective dependency and reactive/proactive aggression and to evaluate individual differences as predisposing factors for aggressive behaviour and emotional dependency. Methods. The Spouse-Specific Dependency Scale (SSDS and the Reactive Proactive Questionnaire (RPQ were administered to a sample of 3375 subjects. Results. In the whole sample, a positive correlation between emotional dependency and proactive aggression was identified. Differences with regard to sex, age group, and geographical distribution were evidenced for the scores of the different scales. Conclusion. A fundamental distinction between reactive and proactive aggression was observed, anchoring proactive aggression more strictly to emotional dependency. Sociocultural and demographical variables, together with the previous structuring of attachment styles, help to determine the scope, frequency, and intensity of the demands made to the partner, as well as to feed the fears of loss, abandonment, or betrayal.

  2. Dry deposition to vegetated surfaces: parametric dependencies

    International Nuclear Information System (INIS)

    Underwood, B.Y.

    1987-12-01

    The dry deposition velocity of airborne pollutants to vegetated surfaces depends on the physico-chemical form of the pollutant, on meteorological conditions (windspeed, atmospheric stability) and on characteristics of the surface cover. This report examines these dependencies, drawing on experimental data and on information from theoretical analyses. A canopy model is outlined which uses first-order closure of the equations for turbulent transport of momentum (or matter), with losses of momentum (or matter) to individual canopy elements parameterised in terms of the mean windspeed: the model has previously been tested against experimental data on an artificial 'grass' canopy. The model is used to elucidate the features of the dependence of deposition velocity on windspeed and on whether the pollutant is in gaseous or particulate form: in the former case, the dependence on the molecular diffusivity of the gas is shown; in the latter case, dependencies on particle diameter and density are deduced. The predictions are related to available measurements. Additional hypotheses are introduced to treat the influence of atmospheric stability on deposition, and the analysis is used to shed light on the somewhat confusing picture that has emerged from past experimental studies. In considering the dependence of deposition velocity on the structural properties of the vegetation, it is established that more parameters than the single one conventionally used -aerodynamic roughness length - are needed to characterise the surface cover. Some indications of the extent of variation in deposition velocity from one type of vegetation to another are elicited from the model. (author)

  3. Affective dependence and aggression: an exploratory study.

    Science.gov (United States)

    Petruccelli, Filippo; Diotaiuti, Pierluigi; Verrastro, Valeria; Petruccelli, Irene; Federico, Roberta; Martinotti, Giovanni; Fossati, Andrea; Di Giannantonio, Massimo; Janiri, Luigi

    2014-01-01

    Emotionally dependent subjects may engage in controlling, restrictive, and aggressive behaviours, which limit their partner's autonomy. The underlying causes of such behaviours are not solely based on levels of aggression, but act as a mean of maintaining the subject's own sense of self-worth, identity, and general functioning. The aim of the paper is to explore the correlation between affective dependency and reactive/proactive aggression and to evaluate individual differences as predisposing factors for aggressive behaviour and emotional dependency. The Spouse-Specific Dependency Scale (SSDS) and the Reactive Proactive Questionnaire (RPQ) were administered to a sample of 3375 subjects. In the whole sample, a positive correlation between emotional dependency and proactive aggression was identified. Differences with regard to sex, age group, and geographical distribution were evidenced for the scores of the different scales. A fundamental distinction between reactive and proactive aggression was observed, anchoring proactive aggression more strictly to emotional dependency. Sociocultural and demographical variables, together with the previous structuring of attachment styles, help to determine the scope, frequency, and intensity of the demands made to the partner, as well as to feed the fears of loss, abandonment, or betrayal.

  4. Grain size dependence of wear in ceramics

    International Nuclear Information System (INIS)

    Wu, C.C.; Rice, R.W.; Johnson, D.; Platt, B.A.

    1985-01-01

    Pin-On-Disk (POD), microwear tests of Al 2 O 3 , MgO, MgAl 2 O 4 , and ZrO 2 , most being dense and essentially single phase, showed the reciprocal of wear following a hall-petch type relationship. However, extrapolation to infinite grain size always gave a lower intercept than most or all single-crystal values; in particular, Al 2 O 3 data projects to a negative intercept. Initial macro wear tests of some of the same Al 2 O 3 materials also indicate a hall-petch type grain-size dependence, but with a greatly reduced grain-size dependence, giving a positive hall-petch intercept. Further, the macrowear grain-size dependence appears to decrease with increased wear. It is argued that thermal expansion anisotropy (of Al 2 O 3 ) significantly affects the grain size dependence of POD wear, in particular, giving a negative intercept, while elastic anisotropy is suggested as a factor in the grain-size dependence of the cubic (MgO, MgAl 2 O 4 , and ZrO 2 ) materials. The reduced grain-size dependence in the macrowear tests is attributed to overlapping wear tracks reducing the effects of enhanced wear damage, e.g., from elastic and thermal expansion anisotropies

  5. Delay discounting of oral morphine and sweetened juice rewards in dependent and non-dependent rats.

    Science.gov (United States)

    Harvey-Lewis, Colin; Perdrizet, Johnna; Franklin, Keith B J

    2014-07-01

    Opioid-dependent humans are reported to show accelerated delay discounting of opioid rewards when compared to monetary rewards. It has been suggested that this may reflect a difference in discounting of consumable and non-consumable goods not specific to dependent individuals. Here, we evaluate the discounting of similar morphine and non-morphine oral rewards in dependent and non-dependent rats We first tested the analgesic and rewarding effects of our morphine solution. In a second experiment, we assigned rats randomly to either dependent or non-dependent groups that, 30 min after daily testing, received 30 mg/kg subcutaneous dose of morphine, or saline, respectively. Delay discounting of drug-free reward was examined prior to initiation of the dosing regimen. We tested discounting of the morphine reward in half the rats and retested the discounting of the drug-free reward in the other half. All tests were run 22.5 h after the daily maintenance dose. Rats preferred the morphine cocktail to the drug-free solution and consumed enough to induce significant analgesia. The control quinine solution did not produce these effects. Dependent rats discounted morphine rewards more rapidly than before dependence and when compared to discounting drug-free rewards. In non-dependent rats both reward types were discounted similarly. These results show that morphine dependence increases impulsiveness specifically towards a drug reward while morphine experience without dependence does not.

  6. Anion exchanger 2 is critical for CD8(+) T cells to maintain pHi homeostasis and modulate immune responses.

    Science.gov (United States)

    Concepcion, Axel R; Salas, January T; Sarvide, Sarai; Sáez, Elena; Ferrer, Alex; López, María; Portu, Ainhoa; Banales, Jesús M; Hervás-Stubbs, Sandra; Oude Elferink, Ronald P J; Prieto, Jesús; Medina, Juan F

    2014-05-01

    Mitogenic stimulation of lymphocytes involves alkalinization of intracellular pH (pHi ). Subsequent pHi regulation may involve HCO3 (-) extrusion through Cl(-) /HCO3 (-) exchangers and/or Na(+) -HCO3 (-) co-transporters with acid-loading capability. Abnormalities in these mechanisms could result in immune dysfunctions, as suggested by the CD8(+) T-cell expansion encountered in mice lacking Ae2 (a widely expressed acid loader with electroneutral and Na(+) -independent Cl(-) /HCO3 (-) anion-exchange activity). Here we report that CD8(+) T cells but not CD4(+) T cells or other lymphocyte populations, are crucially dependent on Ae2 for pHi regulation. While total lymphocytes (including isolated CD4(+) T cells) exhibit Ae1 expression and Na(+) -HCO3 (-) co-transport with acidifying potential, CD8(+) T cells lack these acid-loading mechanisms. In Ae2-KO mice, CD4(+) but not CD8(+) T cells upregulate these potential Ae2 surrogates. As a consequence, Ae2-KO CD8(+) T cells exhibit alkalinized pHi , and dramatically increase their pHi upon CD3 stimulation. Moreover, stimulated Ae2-deficient CD8(+) T cells show enhanced intracellular production of IL-2 and membrane expression of its receptor IL-2Rα, together with increased cell proliferation and activation. These findings demonstrate that CD8(+) T cells are critically dependent on Ae2 for pHi homeostasis and tuning of cell proliferation and activation. Ae2 thus constitutes a novel target to modulate CD8(+) T-cell responses. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Clinical importance of caffeine dependence and abuse.

    Science.gov (United States)

    Ogawa, Naoshi; Ueki, Hirofumi

    2007-06-01

    Caffeine is the most widely consumed psychoactive substance and is a legal stimulant that is readily available to children. Caffeine has occasionally been considered a drug of abuse and the potential for dependence on caffeine has been debated. Presently, due to a paucity of clinical evidence on caffeine dependence or abuse, no such diagnosis is included in the Diagnostic and Statistical Manual of Mental Disorder-fourth edition. The authors present two cases of abuse or dependence on the caffeine contained in 'eutrophic' (energy/nutritional) beverages or caffeine preparations, followed by a review of clinical studies demonstrating evidence that some people can manifest a clinical syndrome of caffeine dependence or abuse. The cases suggest that caffeine can produce a clinical dependence syndrome similar to those produced by other psychoactive substances and has a potential for abuse. In a recent study using a structured interview and the Diagnostic and Statistical Manual of Mental Disorder-fourth edition criteria for substance dependence and abuse, a subset of the general population was found to demonstrate caffeine dependence or caffeine abuse. Therefore, the authors propose that companies or businesses manufacturing or marketing caffeine or products containing caffeine must meet the following guidelines: (i) clearly indicate the caffeine content of products containing comparatively higher quantities of caffeine; (ii) warn that such products should be avoided by infants and children wherever possible, and inform adult consumers about the precise quantity of caffeine that is considered safe for consumption; and (iii) clearly state that consuming large quantities of caffeine and the long-term use of caffeine carry health risks.

  8. Software Dependability and Safety Evaluations ESA's Initiative

    Science.gov (United States)

    Hernek, M.

    ESA has allocated funds for an initiative to evaluate Dependability and Safety methods of Software. The objectives of this initiative are; · More extensive validation of Safety and Dependability techniques for Software · Provide valuable results to improve the quality of the Software thus promoting the application of Dependability and Safety methods and techniques. ESA space systems are being developed according to defined PA requirement specifications. These requirements may be implemented through various design concepts, e.g. redundancy, diversity etc. varying from project to project. Analysis methods (FMECA. FTA, HA, etc) are frequently used during requirements analysis and design activities to assure the correct implementation of system PA requirements. The criticality level of failures, functions and systems is determined and by doing that the critical sub-systems are identified, on which dependability and safety techniques are to be applied during development. Proper performance of the software development requires the development of a technical specification for the products at the beginning of the life cycle. Such technical specification comprises both functional and non-functional requirements. These non-functional requirements address characteristics of the product such as quality, dependability, safety and maintainability. Software in space systems is more and more used in critical functions. Also the trend towards more frequent use of COTS and reusable components pose new difficulties in terms of assuring reliable and safe systems. Because of this, its dependability and safety must be carefully analysed. ESA identified and documented techniques, methods and procedures to ensure that software dependability and safety requirements are specified and taken into account during the design and development of a software system and to verify/validate that the implemented software systems comply with these requirements [R1].

  9. Detecting modularity "smells" in dependencies injected with Java annotations

    NARCIS (Netherlands)

    Roubtsov, S.; Serebrenik, A.; Brand, van den M.G.J.

    2010-01-01

    Dependency injection is a recent programming mechanism reducing dependencies among components by delegating them to an external entity, called a dependency injection framework. An increasingly popular approach to dependency injection implementation relies upon using Java annotations, a special form

  10. The outlook for US oil dependence

    International Nuclear Information System (INIS)

    Greene, D.L.; Jones, D.W.; Leiby, P.N.

    1998-01-01

    Oil dependence is defined as a dynamic problem of short- and long-run market power. The potential monopoly power of an oil cartel depends on its market share and the elasticities of oil supply and demand, while the economic vulnerability of oil-consuming states depends most directly on the quantity of oil imported and the oil cost share of gross domestic product (GDP). Of these factors, only the market share of the Organization of Petroleum Exporting Countries (OPEC) cartel and the rate of growth of world oil demand are clearly different than they were 25 years ago. OPEC still holds the majority of world oil and, in the future, will regain market share. A hypothetical 2-year supply reduction in 2005-2006, similar in size to those of 1973-1974 or 1979-1980, illustrates the potential benefits to OPEC and harm to the US economy of a future oil price shock. OPEC's revenues are estimated to increase by roughly $0.7 trillion, while the US economy loses about $0.5 trillion. Strategic petroleum reserves seem ineffective against a determined, multi-year supply curtailment. Increasing the market's price responsiveness by improving the technologies of oil supply and oil demand can greatly reduce the costs of oil dependence. Each element of this interpretation of the oil dependence problem is well supported by previous studies. This paper's contribution is to unite these elements into a coherent explanation and to point out the enormously important implications for energy policy. (Author)

  11. PSYCHIATRIC COMORBIDITY IN PATIENTS WITH OPIOID DEPENDENCE

    Directory of Open Access Journals (Sweden)

    Shihab Kattukulathil

    2018-02-01

    Full Text Available BACKGROUND Opioid dependence is a major public health problem in Kerala. Presence of psychiatric disorder among opioid dependent patients worsens the scenario. To date no attempts have been made to analyse the magnitude and pattern of comorbid psychiatric disorders in the state. MATERIALS AND METHODS We assessed 30 patients with ICD-10 diagnosis of opioid dependence syndrome for the presence of comorbid psychiatric disorders using structured clinical interview for DSM IV Axis 1 disorder (SCID-1. Patients with opioid withdrawal state, delirium and acute medical emergencies were excluded. RESULTS 56.7% of our subjects had a comorbid psychiatric disorder. Major depressive disorder was the most common one (n=7, 23.3%. Prevalence of other disorders were generalised anxiety disorder (n=6, 20%, bipolar affective disorder (n=3, 10% and schizophrenia (n=1, 3.3%. CONCLUSION Comorbid Psychiatric disorders are highly prevalent in opioid dependence. There is a need for further large sample studies in the areas of comorbidities and in the integrated strategies for the identification and management of both opioid dependence and comorbid psychiatric disorders.

  12. Flavin-Dependent Enzymes in Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Danuta Wojcieszyńska

    2012-12-01

    Full Text Available Statistical studies have demonstrated that various agents may reduce the risk of cancer’s development. One of them is activity of flavin-dependent enzymes such as flavin-containing monooxygenase (FMOGS-OX1, FAD-dependent 5,10-methylenetetrahydrofolate reductase and flavin-dependent monoamine oxidase. In the last decade, many papers concerning their structure, reaction mechanism and role in the cancer prevention were published. In our work, we provide a more in-depth analysis of flavin-dependent enzymes and their contribution to the cancer prevention. We present the actual knowledge about the glucosinolate synthesized by flavin-containing monooxygenase (FMOGS-OX1 and its role in cancer prevention, discuss the influence of mutations in FAD-dependent 5,10-methylenetetrahydrofolate reductase on the cancer risk, and describe FAD as an important cofactor for the demethylation of histons. We also present our views on the role of riboflavin supplements in the prevention against cancer.

  13. Alcohol dependence as a chronic pain disorder

    Science.gov (United States)

    Egli, Mark; Koob, George F.; Edwards, Scott

    2013-01-01

    Dysregulation of pain neurocircuitry and neurochemistry has been increasingly recognized as playing a critical role in a diverse spectrum of diseases including migraine, fibromyalgia, depression, and PTSD. Evidence presented here supports the hypothesis that alcohol dependence is among the pathologies arising from aberrant neurobiological substrates of pain. In this review, we explore the possible influence of alcohol analgesia and hyperalgesia in promoting alcohol misuse and dependence. We examine evidence that neuroanatomical sites involved in the negative emotional states of alcohol dependence also play an important role in pain transmission and may be functionally altered under chronic pain conditions. We also consider possible genetic links between pain transmission and alcohol dependence. We propose an allostatic load model in which episodes of alcohol intoxication and withdrawal, traumatic stressors, and injury are each capable of dysregulating an overlapping set of neural substrates to engender sensory and affective pain states that are integral to alcohol dependence and comorbid conditions such as anxiety, depression, and chronic pain. PMID:22975446

  14. Guarded dependent type theory with coinductive types

    DEFF Research Database (Denmark)

    Bizjak, Aleš; Grathwohl, Hans Bugge; Clouston, Ranald

    2016-01-01

    We present guarded dependent type theory, gDTT, an extensional dependent type theory with a later' modality and clock quantifiers for programming and proving with guarded recursive and coinductive types. The later modality is used to ensure the productivity of recursive definitions in a modular......, type based, way. Clock quantifiers are used for controlled elimination of the later modality and for encoding coinductive types using guarded recursive types. Key to the development of gDTT are novel type and term formers involving what we call delayed substitutions’. These generalise the applicative...... functor rules for the later modality considered in earlier work, and are crucial for programming and proving with dependent types. We show soundness of the type theory with respect to a denotational model....

  15. Temperature dependence of radiation chemistry of polymers

    International Nuclear Information System (INIS)

    Garrett, R.W.; Hill, D.J.T.; Le, T.T.; Milne, K.A.; O'Donnell, J.H.; Perera, S.M.C.; Pomery, P.J.

    1990-01-01

    Chemical reactions which occur during radiolysis of polymers usually show an increase in rate with increasing temperature that can be described by an Arrhenius relationship. The magnitude of the activation energy can vary widely and is affected by physical, as well as chemical, factors. Different reaction rates may be expected in crystalline and amorphous morphologies, and in glassy and rubbery regions. The temperature dependence of radiolysis reactions can be expected to show discontinuities at the glass and melting transitions, T g and T m . The ceiling temperature, T c , for polymerization/depolymerization will also affect the rate of degradation, especially for depropagation to monomer. The temperature for this effect depends on the molecular structure of the polymer. The temperature dependence of free radical reactions can be studied by cryogenic trapping and ESR spectroscopy during thermal profiling. Increased degradation rates at high dose rates can be due to increased temperatures resulting from energy absorption

  16. Great red spot dependence on solar activity

    International Nuclear Information System (INIS)

    Schatten, K.H.

    1979-01-01

    A new inquiry has been made into the question of whether Jupiter's Great Red Spot shows a solar activity dependence. From 1892 to 1947 a clear correlation was present. A dearth of sightings in the seventeenth century, along with the Maunder Minimum, further supports the relation. An anticorrelation, however, from l948 to l967 removed support for such an effect. The old observations have reexamined and recent observations have also been studied. The author reexamines this difficult question and suggests a possible physical mechanism for a Sun-Jovian weather relation. Prinn and Lewis' conversion reaction of Phosphine gas to triclinic red phosphorous crystals is a reaction dependent upon solar radiation. It may explain the dependence found, as well as the striking appearance of the Great Red Spot in the UV

  17. Socio-emotional factors in alcohol dependence.

    Science.gov (United States)

    Tikka, Deyashini Lahiri; Ram, Daya; Dubey, Indu; Tikka, Sai Krishna

    2014-04-01

    Alcohol-dependent patients are traditionally believed to have insecure attachment styles, higher anger expression, and lower self-esteem. There is a need to study them together. To understand the relationships amongst various of the socio-emotional factors. Forty male patients with Alcohol dependence syndrome and 40 matched healthy controls (General Health Questionnaire-12 score Relationship Scale Questionnaire), anger domains (on State Trait Anger Expression Inventory), and self-esteem (on Rosenberg Self-esteem Scale). Comparison using independent samples t test and chi square test; correlation using Pearson's correlation coefficient. Patients had significantly higher anger expression, 'anger in' and 'anger out,' and lower self-esteem than healthy controls. Severity of alcohol dependence had significant correlation with 'anger out,' and self-esteem had significant negative correlation with anger expression. The present study suggests that the socio-emotional factors studied are developmentally linked to each other.

  18. Context-dependent memory: colour versus odour.

    Science.gov (United States)

    Pointer, S C; Bond, N W

    1998-06-01

    An olfactory stimulus and a visual stimulus were employed in a context-dependent memory study using a prose passage as the to-be-remembered item. Ninety-five university students (aged 17-35 years) learned the passage of prose in the presence of one of the stimuli and were then asked to recall the passage with the original context either reinstated or not reinstated. The results revealed a significant context-dependent memory effect for the olfactory cue but not for the visual cue. They demonstrate support for the effectiveness of odours as context cues and it is suggested that context-dependent memory processes may underlie the formation and retrieval of odour-evoked autobiographical memories.

  19. Modelling dependable systems using hybrid Bayesian networks

    International Nuclear Information System (INIS)

    Neil, Martin; Tailor, Manesh; Marquez, David; Fenton, Norman; Hearty, Peter

    2008-01-01

    A hybrid Bayesian network (BN) is one that incorporates both discrete and continuous nodes. In our extensive applications of BNs for system dependability assessment, the models are invariably hybrid and the need for efficient and accurate computation is paramount. We apply a new iterative algorithm that efficiently combines dynamic discretisation with robust propagation algorithms on junction tree structures to perform inference in hybrid BNs. We illustrate its use in the field of dependability with two example of reliability estimation. Firstly we estimate the reliability of a simple single system and next we implement a hierarchical Bayesian model. In the hierarchical model we compute the reliability of two unknown subsystems from data collected on historically similar subsystems and then input the result into a reliability block model to compute system level reliability. We conclude that dynamic discretisation can be used as an alternative to analytical or Monte Carlo methods with high precision and can be applied to a wide range of dependability problems

  20. Temperature Dependence of Factors Controlling Isoprene Emissions

    Science.gov (United States)

    Duncan, Bryan N.; Yoshida, Yasuko; Damon, Megan R.; Douglass, Anne R.; Witte, Jacquelyn C.

    2009-01-01

    We investigated the relationship of variability in the formaldehyde (HCHO) columns measured by the Aura Ozone Monitoring Instrument (OMI) to isoprene emissions in the southeastern United States for 2005-2007. The data show that the inferred, regional-average isoprene emissions varied by about 22% during summer and are well correlated with temperature, which is known to influence emissions. Part of the correlation with temperature is likely associated with other causal factors that are temperature-dependent. We show that the variations in HCHO are convolved with the temperature dependence of surface ozone, which influences isoprene emissions, and the dependence of the HCHO column to mixed layer height as OMI's sensitivity to HCHO increases with altitude. Furthermore, we show that while there is an association of drought with the variation in HCHO, drought in the southeastern U.S. is convolved with temperature.

  1. Time dependent policy-based access control

    DEFF Research Database (Denmark)

    Vasilikos, Panagiotis; Nielson, Flemming; Nielson, Hanne Riis

    2017-01-01

    also on other attributes of the environment such as the time. In this paper, we use systems of Timed Automata to model distributed systems and we present a logic in which one can express time-dependent policies for access control. We show how a fragment of our logic can be reduced to a logic......Access control policies are essential to determine who is allowed to access data in a system without compromising the data's security. However, applications inside a distributed environment may require those policies to be dependent on the actual content of the data, the flow of information, while...... that current model checkers for Timed Automata such as UPPAAL can handle and we present a translator that performs this reduction. We then use our translator and UPPAAL to enforce time-dependent policy-based access control on an example application from the aerospace industry....

  2. Length dependent properties of SNS microbridges

    International Nuclear Information System (INIS)

    Sauvageau, J.E.; Jain, R.K.; Li, K.; Lukens, J.E.; Ono, R.H.

    1985-01-01

    Using an in-situ, self-aligned deposition scheme, arrays of variable length SNS junctions in the range of 0.05 μm to 1 μm have been fabricated. Arrays of SNS microbridges of lead-copper and niobium-copper fabricated using this technique have been used to study the length dependence, at constant temperature, of the critical current I and bridge resistance R /SUB d/ . For bridges with lengths pounds greater than the normal metal coherence length xi /SUB n/ (T), the dependence of I /SUB c/ on L is consistent with an exponential dependence on the reduced length l=L/xi /SUB n/ (T). For shorter bridges, deviations from this behavior is seen. It was also found that the bridge resistance R /SUB d/ does not vary linearly with the geometric bridge length but appears to approach a finite value as L→O

  3. Practical Reflection and Metaprogramming for Dependent Types

    DEFF Research Database (Denmark)

    Christiansen, David Raymond

    to program in these embedded languages. Interpreters and compilers must always take these invariants into account at each stage, and authors of embedded languages must work hard to relieve users of the burden of proving these properties. Idris is a dependently typed functional programming language whose......Embedded domain-specific languages are special-purpose programming languages that are implemented within existing generalpurpose programming languages. Dependent type systems allow strong invariants to be encoded in representations of domain-specific languages, but it can also make it difficult...... semantics are given by elaboration to a core dependent type theory through a tactic language. This dissertation introduces elaborator reflection, in which the core operators of the elaborator are realized as a type of computations that are executed during the elaboration process of Idris itself, along...

  4. [Affective dependency and psychiatry: a discord].

    Science.gov (United States)

    Versaevel, C

    2011-02-01

    The term "loving dependence" is increasingly used by professionals of the relation of help and the patients themselves. It joins in the wider spectre of the interpersonal dependency. More and more patients suffering from this disorder are coming for psychiatric consultation. However, this notion remains vague and absent in the vocabulary of the psychiatrists. Globally, this term describes the functioning of certain patients who present a fear of not being loved and a dependency on another person. The fear of not being loved provokes a fear of abandonment or incites development of strategies to be loved (seduce, help). Dependency on another person is a consequence of the lack of confidence in the capabilities of the individual. The other person reassures them because this person does what the patient is afraid of doing, because he/she does not feel capable. The lack of confidence in own's capabilities can also incite the individual to become a perfectionist and successful. The fear of not being loved and of not being competent is determined partly in the person's childhood. These impressions are real and/or the individuals are hypersensitive. The article describes the emotional, cognitive and behavioural levels, the various types of interpersonal dependency: dependences of type "umbilical cord", "rescuer", "stereotype" and "against dependence". The objective is to specify the concept better on clinical level, with the aim of defining criteria and pathological limits. This is the first stage before beginning rigorous scientific research. The stakes are high. There are relationships with anxiety, depressive disorders, alcoholism, food behaviour disorders, suicide and somatic pathologies. Dependency seems to be the consequence of a pathological expression of the normal dimensions of the personality: the need to be loved and valued (admired). The onset of dependency occurs in stages, when the person is weakened by events of life or by depression. The impression not to

  5. Denotational semantics for guarded dependent type theory

    DEFF Research Database (Denmark)

    Bizjak, Aleš; Møgelberg, Rasmus Ejlers

    2018-01-01

    We present a new model of Guarded Dependent Type Theory (GDTT), a type theory with guarded recursion and multiple clocks in which one can program with, and reason about coinductive types. Productivity of recursively defined coinductive programs and proofs is encoded in types using guarded recursion......, crucial for programming with coinductive types, types must be interpreted as presheaves orthogonal to the object of clocks. In the case of dependent types, this translates to a unique lifting condition similar to the one found in homotopy theoretic models of type theory. Since the universes defined...... by inclusions of clock variable contexts commute on the nose with type operations on the universes....

  6. The other side of oil dependence

    International Nuclear Information System (INIS)

    Mitchell, John V.

    2006-01-01

    Policy makers in oil-importing countries express concern about political instability in exporting countries, and their willingness to invest for future exports. In fact, the petroleum exporting countries are more dependent on oil trade than the importing countries, and can be expected to invest to support this trade. They depend on growing foreign currency earnings and government revenue to sustain their economic growth and face difficult adjustments when, in the future, petroleum production ceases to grow. Failure to invest in the petroleum sector would accelerate their difficulties, but they also need to develop an export-oriented, tax generating growth outside petroleum

  7. Integrable Time-Dependent Quantum Hamiltonians

    Science.gov (United States)

    Sinitsyn, Nikolai A.; Yuzbashyan, Emil A.; Chernyak, Vladimir Y.; Patra, Aniket; Sun, Chen

    2018-05-01

    We formulate a set of conditions under which the nonstationary Schrödinger equation with a time-dependent Hamiltonian is exactly solvable analytically. The main requirement is the existence of a non-Abelian gauge field with zero curvature in the space of system parameters. Known solvable multistate Landau-Zener models satisfy these conditions. Our method provides a strategy to incorporate time dependence into various quantum integrable models while maintaining their integrability. We also validate some prior conjectures, including the solution of the driven generalized Tavis-Cummings model.

  8. Fermions in interaction with time dependent fields

    International Nuclear Information System (INIS)

    Falkensteiner, P.; Grosse, H.

    1988-01-01

    We solve a two dimensional model describing the interaction of fermions with time dependent external fields. We work out the second quantized formulation and obtain conditions for equivalence of representations at different times. This implies the existence of sectors which describe charged states. We obtain the time dependence of charges and observe that charge differences become integer for unitary equivalent states. For scattering we require the equivalence of in- and out-representations; nevertheless charged sectors may be reached by suitable interactions and ionization is possible. 20 refs. (Author)

  9. A Delicate Balance of Different Dependencies

    DEFF Research Database (Denmark)

    Brincker, Benedikte

    , the region holds promises of an abundance of natural resources and the prospect of new international trade routes. This draws attention to one particular country: Greenland. Greenland is part of the Kingdom of Denmark – but it has for many years witnessed moves towards national independence. These calls...... of balancing different dependencies. In this perspective, Greenland is the case in extremis. The prospect of Greenland seceding from the Kingdom of Denmark relies upon it becoming embedded in the “international community of sovereign nation states” thus balancing different dependencies ‐ while also...

  10. Temperature dependence of radiation effects in polyethylene

    International Nuclear Information System (INIS)

    Wu, G; Katsumura, Y.; Kudoh, H.; Morita, Y.; Seguchi, T.

    2000-01-01

    Temperature dependence of crosslinking and gas evolution under γ-irradiation was studied for high-density and low-density polyethylene samples in the 30-360degC range. It was found that crosslinking was the predominant process up to 300degC and the gel point decreased with increasing temperature. At above 300degC, however, the gel fraction at a given dose decreased rapidly with temperature and the action of radiation turned to enhance polyethylene degradation. Yields of H 2 and hydrocarbon gases increased with temperature and the compositions of hydrocarbons were dose dependent. (author)

  11. Investigations of Low Temperature Time Dependent Cracking

    Energy Technology Data Exchange (ETDEWEB)

    Van der Sluys, W A; Robitz, E S; Young, B A; Bloom, J

    2002-09-30

    The objective of this project was to investigate metallurgical and mechanical phenomena associated with time dependent cracking of cold bent carbon steel piping at temperatures between 327 C and 360 C. Boiler piping failures have demonstrated that understanding the fundamental metallurgical and mechanical parameters controlling these failures is insufficient to eliminate it from the field. The results of the project consisted of the development of a testing methodology to reproduce low temperature time dependent cracking in laboratory specimens. This methodology was used to evaluate the cracking resistance of candidate heats in order to identify the factors that enhance cracking sensitivity. The resultant data was integrated into current available life prediction tools.

  12. Event dependent sampling of recurrent events

    DEFF Research Database (Denmark)

    Kvist, Tine Kajsa; Andersen, Per Kragh; Angst, Jules

    2010-01-01

    The effect of event-dependent sampling of processes consisting of recurrent events is investigated when analyzing whether the risk of recurrence increases with event count. We study the situation where processes are selected for study if an event occurs in a certain selection interval. Motivation...... retrospective and prospective disease course histories are used. We examine two methods to correct for the selection depending on which data are used in the analysis. In the first case, the conditional distribution of the process given the pre-selection history is determined. In the second case, an inverse...

  13. A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence.

    Science.gov (United States)

    Grucza, Richard A; Wang, Jen C; Stitzel, Jerry A; Hinrichs, Anthony L; Saccone, Scott F; Saccone, Nancy L; Bucholz, Kathleen K; Cloninger, C Robert; Neuman, Rosalind J; Budde, John P; Fox, Louis; Bertelsen, Sarah; Kramer, John; Hesselbrock, Victor; Tischfield, Jay; Nurnberger, John I; Almasy, Laura; Porjesz, Bernice; Kuperman, Samuel; Schuckit, Marc A; Edenberg, Howard J; Rice, John P; Goate, Alison M; Bierut, Laura J

    2008-12-01

    A nonsynonymous coding polymorphism, rs16969968, of the CHRNA5 gene that encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence. The goal of this study was to examine the association of this variant with cocaine dependence. Genetic association analysis was performed in two independent samples of unrelated case and control subjects: 1) 504 European Americans participating in the Family Study on Cocaine Dependence (FSCD) and 2) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholism (COGA). In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele, p = .0045, assuming an additive genetic model), but in the reverse direction compared with that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD. The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways.

  14. Sodium-bicarbonate cotransporter NBCn1 in the kidney medullary thick ascending limb cell line is upregulated under acidic conditions and enhances ammonium transport.

    Science.gov (United States)

    Lee, Soojung; Lee, Hye Jeong; Yang, Han Soo; Thornell, Ian M; Bevensee, Mark O; Choi, Inyeong

    2010-09-01

    In this study, we examined the effect of bicarbonate transporters on ammonium/ammonia uptake in the medullary thick ascending limb cell line ST-1. Cells were treated with 1 mm ouabain and 0.2 mM bumetanide to minimize carrier-mediated NH(4)(+) transport, and the intracellular accumulation of (14)C-methylammonium/methylammonia ((14)C-MA) was determined. In CO(2)/HCO(3)(-)-free solution, cells at normal pH briefly accumulated (14)C-MA over 7 min and reached a plateau. In CO(2)/HCO(3)(-) solution, however, cells markedly accumulated (14)C-MA over the experimental period of 30 min. This CO(2)/HCO(3)(-)-dependent accumulation was reduced by the bicarbonate transporter blocker, 4,4-diisothiocyanatostilbene-2,2-disulfonate (DIDS; 0.5 mM). Replacing Cl(-) with gluconate reduced the accumulation, but the reduction was more substantial in the presence of DIDS. Incubation of cells at pH 6.8 (adjusted with NaHCO(3) in 5% CO(2)) for 24 h lowered the mean steady-state intracellular pH to 6.96, significantly lower than 7.28 for control cells. The presence of DIDS reduced (14)C-MA accumulation in control conditions but had no effect after acidic incubation. Immunoblotting showed that NBCn1 was upregulated after acidic incubation and in NH(4)Cl-containing media. The Cl(-)-HCO(3)(-) exchanger AE2 was present, but its expression remained unaffected by acidic incubation. Expressed in Xenopus oocytes, NBCn1 increased carrier-mediated (14)C-MA transport, which was abolished by replacing Na(+). Two-electrode voltage clamp of oocytes exhibited negligible current after NH(4)Cl application. These results suggest that DIDS-sensitive HCO(3)(-) extrusion normally governs NH(4)(+)/NH(3) uptake in the medullary thick ascending limb cells. We propose that, in acidic conditions, DIDS-sensitive HCO(3)(-) extrusion is inactivated, while NBCn1 is upregulated to stimulate NH(4)(+) transport.

  15. The spatial geochemical characteristics of groundwater and surface in the Tuul River basin, Ulaanbatar, Mongolia

    Science.gov (United States)

    Batdelger, Odsuren; Tsujimura, Maki; Zorigt, Byambasuren; Togtokh, Enkhjargal

    2017-04-01

    The capital city, Ulaanbaatar, is located along the Tuul River and its water supply totally dependent on the groundwater, which comes from the aquifer of the Tuul River. Due to the rapid growth of the population and the increasing human pressures in this basin, water quality has been deteriorating and has become a crucial issue for sustainable environmental and socio-economic development. Hydro-chemical and stable isotope tracing approaches were applied into the groundwater and surface water in order to study geochemical characteristics and groundwater and surface water interaction. The Tuul River water was mostly characterized by the Ca-HCO3 type, spatially variable and it changed into Ca-Na-HCO3 type in the downstream of the city after wastewater (WW) meets the river. Also, electrical conductivity (EC) values of Tuul River are increasing gradually with distance and it increased more than 2 times after WW meets the stream, therefore anthropogenic activities influence to the downstream of the river. The dominant hydro-chemical facies of groundwater were the Ca-HCO3 type, which represents 83% of the total analyzed samples, while Ca- HCO3-Cl-NO3, Na-HCO3, Ca-HCO3-SO4 each represent 4%, and Ca-mixed and Ca-Mg-HCO3 each represent 2% of the total samples. This suggests that groundwater chemistry is controlled by rock-water interaction and anthropogenic pollution. The floodplain groundwater chemical characteristics were similar to Tuul River water and showing lowest EC values. Groundwater far from floodplain showed higher EC (mean value of 498 μs/cm) values than river waters and floodplain groundwater. Also, different kinds of hydro-chemical facies were observed. The stable isotopic compositions revealed less evaporation effect on the groundwater and surface water, as well as an altitude effect in the river water. The similarity of stable isotopes and chemical characteristics of floodplain groundwater and river water suggests that alluvial groundwater is recharged by

  16. Comparing of the Reaction Time in Substance-Dependent and Non-Dependent Individuals

    Directory of Open Access Journals (Sweden)

    Mohammad Narimani

    2012-11-01

    Full Text Available Aim: The aim of this study was to compare the simple, selective, and discrimination reaction time in substance-dependent and non-dependent individuals. Method: In this causal-comparative study, the population included of 425 males (opium and crystal dependents who were referred to addiction rehabilitation centers in Tabriz. By random sampling, 16 opium dependents, 16 crystal dependents, and 16 non-dependent individuals with no history of dependency as the compare group were selected. All groups peered in age, and marital status. For gathering data, “Addicts Admit Questionnaire” and laboratory device known as the "Reaction Time Assay" have been used. Results: The results of this study showed that there are significant differences among all groups in simple reaction time, choice reaction time and reaction time to auditory stimuli, but no significant difference in discrimination reaction time and reaction time to visual stimulus observed. Conclusion: The reaction time of substance-dependent groups is slower than non-dependent groups.

  17. Wave function for time-dependent harmonically confined electrons in a time-dependent electric field.

    Science.gov (United States)

    Li, Yu-Qi; Pan, Xiao-Yin; Sahni, Viraht

    2013-09-21

    The many-body wave function of a system of interacting particles confined by a time-dependent harmonic potential and perturbed by a time-dependent spatially homogeneous electric field is derived via the Feynman path-integral method. The wave function is comprised of a phase factor times the solution to the unperturbed time-dependent Schrödinger equation with the latter being translated by a time-dependent value that satisfies the classical driven equation of motion. The wave function reduces to that of the Harmonic Potential Theorem wave function for the case of the time-independent harmonic confining potential.

  18. Time dependent resonating Hartree-Bogoliubov theory

    International Nuclear Information System (INIS)

    Nishiyama, Seiya; Fukutome, Hideo.

    1989-01-01

    Very recently, we have developed a theory of excitations in superconducting Fermion systems with large quantum fluctuations that can be described by resonance of time dependent non-orthogonal Hartree-Bogoliubov (HB) wave functions with different correlation structures. We have derived a new kind of variation equation called the time dependent Resonating HB equation, in order to determine both the time dependent Resonating HB wave functions and coefficients of a superposition of the HB wave functions. Further we have got a new approximation for excitations from time dependent small fluctuations of the Resonating HB ground state, i.e., the Resonating HB RPA. The Res HB RPA equation is represented in a given single particle basis. It, however, has drawbacks that the constraints for the Res HB RPA amplitudes are not taken into account and the equation contains equations which are not independent. We shall derive another form of the Res HB RPA equation eliminating these drawbacks. The Res HB RPA gives a unified description of the vibrons and resonons and their interactions. (author)

  19. Problems Identifying Independent and Dependent Variables

    Science.gov (United States)

    Leatham, Keith R.

    2012-01-01

    This paper discusses one step from the scientific method--that of identifying independent and dependent variables--from both scientific and mathematical perspectives. It begins by analyzing an episode from a middle school mathematics classroom that illustrates the need for students and teachers alike to develop a robust understanding of…

  20. Benford's law and continuous dependent random variables

    Science.gov (United States)

    Becker, Thealexa; Burt, David; Corcoran, Taylor C.; Greaves-Tunnell, Alec; Iafrate, Joseph R.; Jing, Joy; Miller, Steven J.; Porfilio, Jaclyn D.; Ronan, Ryan; Samranvedhya, Jirapat; Strauch, Frederick W.; Talbut, Blaine

    2018-01-01

    Many mathematical, man-made and natural systems exhibit a leading-digit bias, where a first digit (base 10) of 1 occurs not 11% of the time, as one would expect if all digits were equally likely, but rather 30%. This phenomenon is known as Benford's Law. Analyzing which datasets adhere to Benford's Law and how quickly Benford behavior sets in are the two most important problems in the field. Most previous work studied systems of independent random variables, and relied on the independence in their analyses. Inspired by natural processes such as particle decay, we study the dependent random variables that emerge from models of decomposition of conserved quantities. We prove that in many instances the distribution of lengths of the resulting pieces converges to Benford behavior as the number of divisions grow, and give several conjectures for other fragmentation processes. The main difficulty is that the resulting random variables are dependent. We handle this by using tools from Fourier analysis and irrationality exponents to obtain quantified convergence rates as well as introducing and developing techniques to measure and control the dependencies. The construction of these tools is one of the major motivations of this work, as our approach can be applied to many other dependent systems. As an example, we show that the n ! entries in the determinant expansions of n × n matrices with entries independently drawn from nice random variables converges to Benford's Law.

  1. Time-dependent Dyson orbital theory

    NARCIS (Netherlands)

    Gritsenko, O.V.; Baerends, E.J.

    2016-01-01

    Although time-dependent density functional theory (TDDFT) has become the tool of choice for real-time propagation of the electron density ρN(t) of N-electron systems, it also encounters problems in this application. The first problem is the neglect of memory effects stemming from the, in TDDFT

  2. State Dependence in Unemployment among Danish Immigrants

    DEFF Research Database (Denmark)

    Ahmad, Nisar

    This study examines the extent state dependence among unemployed Danish immigrants in a dynamic discrete choice framework. Three alternative methodologies are employed to control for the problem of the initial condition. The empirical findings show that there is a considerable correlation between...

  3. Smartphone dependence classification using tensor factorization

    Science.gov (United States)

    Kim, Yejin; Yook, In Hye; Yu, Hwanjo; Kim, Dai-Jin

    2017-01-01

    Excessive smartphone use causes personal and social problems. To address this issue, we sought to derive usage patterns that were directly correlated with smartphone dependence based on usage data. This study attempted to classify smartphone dependence using a data-driven prediction algorithm. We developed a mobile application to collect smartphone usage data. A total of 41,683 logs of 48 smartphone users were collected from March 8, 2015, to January 8, 2016. The participants were classified into the control group (SUC) or the addiction group (SUD) using the Korean Smartphone Addiction Proneness Scale for Adults (S-Scale) and a face-to-face offline interview by a psychiatrist and a clinical psychologist (SUC = 23 and SUD = 25). We derived usage patterns using tensor factorization and found the following six optimal usage patterns: 1) social networking services (SNS) during daytime, 2) web surfing, 3) SNS at night, 4) mobile shopping, 5) entertainment, and 6) gaming at night. The membership vectors of the six patterns obtained a significantly better prediction performance than the raw data. For all patterns, the usage times of the SUD were much longer than those of the SUC. From our findings, we concluded that usage patterns and membership vectors were effective tools to assess and predict smartphone dependence and could provide an intervention guideline to predict and treat smartphone dependence based on usage data. PMID:28636614

  4. Texas Employer 1996 Dependent Care Survey.

    Science.gov (United States)

    Ruggiere, Paul; Glass, James

    Many employers have enacted "family-friendly benefits" in response to demands placed on their employees by the stress of caring for children or aging parents. The Employer Dependent Care Survey measured the prevalence of flexible work arrangements and child care and elder care benefits in Texas. Participating were 1,331 out of 6,500…

  5. Halden project activities on software dependability

    International Nuclear Information System (INIS)

    Dahll, G.; Sivertsen.

    1994-01-01

    Since 1977, the OECD Halden Reactor Project has been working in the field of software dependability. Special emphasis has been put on the use of software in safety critical systems. All phases in software development, from specification through software development, verification, and validation have been covered and are discussed in this article

  6. Biological repair with time-dependent irradiation

    International Nuclear Information System (INIS)

    Broyles, A.A.; Shapiro, C.S.

    1985-01-01

    Recent experiments have provided new data that explore the effectiveness of biological repair in assessing damage due to exposures from ionizing radiation. These data are mainly from experiments conducted at constant dose rates, to study the effectiveness per unit dose of different dose rates. Here, we develop new formulae to estimate the effectiveness of an arbitrary time-dependent dose rate exposure

  7. Organizational Change, Absenteeism, and Welfare Dependency

    Science.gov (United States)

    Roed, Knut; Fevang, Elisabeth

    2007-01-01

    Based on Norwegian register data, we set up a multivariate mixed proportional hazard model (MMPH) to analyze nurses' pattern of work, sickness absence, nonemployment, and social insurance dependency from 1992 to 2000, and how that pattern was affected by workplace characteristics. The model is estimated by means of the nonparametric…

  8. Mycorrhizal dependency of laurel (Ocotea sp.)

    International Nuclear Information System (INIS)

    Sierra-Escobar, Jorge A; Castro Restrepo, Dagoberto; Osorio Vega, Walter

    2009-01-01

    A greenhouse experiment was carried out to determine the mycorrhizal dependency of laurel (>Ocotea sp.). In order to do this, a completely randomized experimental design was used, with six treatments in a factorial array of 3 x 2 and five repetitions. The treatments involved a combination of three Phosphorus (P) levels in soil solution (0.002, 0.02 and 0.2 mg L-1) and two levels of mycorrhizal inoculation, either inoculated or non-inoculated with Glomus aggregatum Schenck and Smith. The leaf P content as a function of time was used as an output variable. Shoot dry matter, shoot P content, mycorrhizal colonization of roots, and mycorrhizal dependence were measured at harvest. The results indicated that the leaf P content increased significantly when using the mycorrhizal inoculation in laurel at P level 0.2 mg L -1, but not in the other P levels, on some of the sampling days. Shoot dry weight and total plant P content did not increase at all levels of soil available P. Mycorrhizal dependency of laurel reached 28%, which allows this species to be classified as moderately dependent on mycorrhiza.

  9. Probabilistic calculation for angular dependence collision

    International Nuclear Information System (INIS)

    Villarino, E.A.

    1990-01-01

    This collision probabilistic method is broadly used in cylindrical geometry (in one- or two-dimensions). It constitutes a powerful tool for the heterogeneous Response Method where, the coupling current is of the cosine type, that is, without angular dependence at azimuthal angle θ and proportional to μ (cosine of the θ polar angle). (Author) [es

  10. Stress Disrupts Context-Dependent Memory

    Science.gov (United States)

    Schwabe, Lars; Bohringer, Andreas; Wolf, Oliver T.

    2009-01-01

    Memory is facilitated when the retrieval context resembles the learning context. The brain structures underlying contextual influences on memory are susceptible to stress. Whether stress interferes with context-dependent memory is still unknown. We exposed healthy adults to stress or a control procedure before they learned an object-location task…

  11. History-dependent stochastic Petri nets

    NARCIS (Netherlands)

    Schonenberg, H.; Sidorova, N.; Aalst, van der W.M.P.; Hee, van K.M.; Pnueli, A.; Virbitskaite, I.; Voronkov, A.

    2010-01-01

    Stochastic Petri Nets are a useful and well-known tool for performance analysis. However, an implicit assumption in the different types of Stochastic Petri Nets is the Markov property. It is assumed that a choice in the Petri net only depends on the current state and not on earlier choices. For many

  12. Evaluation Framework for Dependable Mobile Learning Scenarios

    Science.gov (United States)

    Bensassi, Manel; Laroussi, Mona

    2014-01-01

    The goal of the dependability analysis is to predict inconsistencies and to reveal ambiguities and incompleteness in the designed learning scenario. Evaluation, in traditional learning design, is generally planned after the execution of the scenario. In mobile learning, this stage becomes too difficult and expensive to apply due to the complexity…

  13. Spatial dependence of pair correlations (nuclear scissors)

    International Nuclear Information System (INIS)

    Bal'butsev, E.B.; Malov, L.A.

    2009-01-01

    The solution of time-dependent Hartree-Fock-Bogolyubov equations by the Wigner function moments method leads to the appearance of low-lying modes whose description requires accurate knowledge of the anomalous density matrix. It is shown that calculations with the Woods-Saxon potential satisfy this requirement

  14. The dependency and contingency of politics

    DEFF Research Database (Denmark)

    Triantafillou, Peter

    2016-01-01

    differences which make any analytical synthesis both a difficult and a questionable endeavour. In particular, whereas historical institutionalism seeks to explain the present in terms of its dependence on past events, genealogy seeks to provoke the present by demonstrating its historical contingency. In spite...

  15. Quantification of Seepage in Groundwater Dependent Wetlands

    DEFF Research Database (Denmark)

    Johansen, Ole; Beven, Keith; Jensen, Jacob Birk

    2018-01-01

    Restoration and management of groundwater dependent wetlands require tools for quantifying the groundwater seepage process. A method for determining point estimates of the groundwater seepage based on water level observations is tested. The study is based on field data from a Danish rich fen...

  16. Scheduling with time-dependent execution times

    NARCIS (Netherlands)

    Woeginger, G.J.

    1995-01-01

    We consider systems of tasks where the task execution times are time-dependent and where all tasks have some common deadline. We describe how to compute in polynomial time a schedule that minimizes the number of late tasks. This answers a question raised in a recent paper by Ho, Leung and Wei.

  17. Hartree--Fock time-dependent problem

    Energy Technology Data Exchange (ETDEWEB)

    Bove, A; Fano, G [Bologna Univ. (Italy). Istituto di Fisica; Istituto Nazionale di Fisica Nucleare, Bologna (Italy)); Da Prato, G [Rome Univ. (Italy). Istituto di Matematica

    1976-06-01

    A previous result is generalized. An existence and uniqueness theorem is proved for the Hartree--Fock time-dependent problem in the case of a finite Fermi system interacting via a two body potential which is supposed to be dominated by the kinetic energy part of the one-particle Hamiltonian.

  18. Agreement, dependencies, and Surface Correspondence in Obolo ...

    African Journals Online (AJOL)

    This approach seems quite generalisable, as this paper demonstrates by applying it to a long-distance voicing dependency in Afrikaans (Coetzee 2014), in which root-medial voiced obstruents may not occur when this would produce disagreement with a voiceless root-initial obstruent. Keywords: harmony, nasality, Obolo, ...

  19. Chewing Maintains Hippocampus-Dependent Cognitive Function.

    Science.gov (United States)

    Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2015-01-01

    Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research.

  20. Eye metrics for task-dependent automation

    NARCIS (Netherlands)

    Imants, P.; Greef, T.E. de

    2014-01-01

    Future air traffic is expected to grow increasingly, opening up a gap for task dependent automation and adaptive interfaces, helping the Air Traffic Controller to cope with fluctuating workloads. One of the challenging factors in the application of such intelligent systems concerns the question what

  1. Eye Metrics for Task-Dependent Automation

    NARCIS (Netherlands)

    Imants, P.; de Greef, T.F.A.

    2014-01-01

    Future air traffic is expected to grow increasingly, opening up a gap for task dependent automation and adaptive interfaces, helping the Air Traffic Controller to cope with fluctuating workloads. One of the challenging factors in the application of such intelligent systems concerns the question what

  2. Parameters Evaluation of PLC Dependability and Safety

    Directory of Open Access Journals (Sweden)

    Juraj Zdansky

    2006-01-01

    Full Text Available This paper is focused on evaluation of dependability and safety parameters of PLC (Programmable Logic Controller. Achievement of requested level of these parameters is an application assumption for using PLC in control of safety critical processes. Evaluation of these parameters can be made on the base of suitable model and it can be influenced by system architecture when necessary.

  3. Investigation Of Temperature Dependent Characteristics Of ...

    African Journals Online (AJOL)

    The structure, magnetization and magnetostriction of Laves phase compound TbCo2 were investigated by temperature dependent high resolution neutron powder diffraction. The compound crystallizes in the cubic Laves phase C15 structure above its Curie temperature, TC and exhibits a rhombohedral distortion (space ...

  4. Temperature Dependent Models of Semiconductor Devices for ...

    African Journals Online (AJOL)

    The paper presents an investigation of the temperature dependent model of a diode and bipolar transistor built-in to the NAP-2 program and comparison of these models with experimentally measured characteristics of the BA 100 diode and BC 109 transistor. The detail of the modelling technique has been discussed and ...

  5. and density-dependent quark mass model

    Indian Academy of Sciences (India)

    Since a fair proportion of such dense proto stars are likely to be ... the temperature- and density-dependent quark mass (TDDQM) model which we had em- ployed in .... instead of Tc ~170 MeV which is a favoured value for the ud matter [26].

  6. Cultural Dependency in Canada's Feature Film Industry.

    Science.gov (United States)

    Pendakur, Manjunath

    1981-01-01

    Examines the ownership and policies of the dominant firms in the Canadian film market to explain Canada's dependence on imported films. Demonstrates how the economic relations existing between Canadian and U.S. film industries limit the profitability of films made in Canada. (JMF)

  7. Efficient bootstrap with weakly dependent processes

    NARCIS (Netherlands)

    Bravo, Francesco; Crudu, Federico

    The efficient bootstrap methodology is developed for overidentified moment conditions models with weakly dependent observation. The resulting bootstrap procedure is shown to be asymptotically valid and can be used to approximate the distributions of t-statistics, the J-statistic for overidentifying

  8. Predictive labeling with dependency pairs using SAT

    NARCIS (Netherlands)

    Koprowski, A.; Middeldorp, A.; Pfenning, F.

    2007-01-01

    This paper combines predictive labeling with dependency pairs and reports on its implementation. Our starting point is the method of proving termination of rewrite systems using semantic labeling with infinite models in combination with lexicographic path orders. We replace semantic labeling with

  9. Small dependencies and large actuarial risks

    NARCIS (Netherlands)

    Albers, Willem/Wim; Kallenberg, W.C.M.; Lukocius, V.

    2006-01-01

    Methods for computing risk measures such as stop-loss premiums tacitly assume independence of the underlying individual risks. From earlier studies it is already known that this assumption can lead to huge errors even when only small dependencies occur. In the present paper a general model is

  10. Temperature dependence of PZT film optical properties

    Czech Academy of Sciences Publication Activity Database

    Deineka, Alexander; Jastrabík, Lubomír; Suchaneck, G.; Gerlach, G.

    11-12, - (2001), s. 352-354 ISSN 0447-6441 R&D Projects: GA ČR GA202/00/1425; GA MŠk LN00A015 Institutional research plan: CEZ:AV0Z1010914 Keywords : refractive index profile * PZT film * temperature dependence of optical properties Subject RIV: BH - Optics, Masers, Lasers

  11. Pressure dependence of the spark constant

    Energy Technology Data Exchange (ETDEWEB)

    Hess, H; Radtke, R; Deparade, W [Akademie der Wissenschaften der DDR, Berlin. Zentralinstitut fuer Elektronenphysik

    1978-02-21

    The author's theory on the development of LTE plasmas in low-inductance spark discharges has proved to be a useful tool in predicting the electric behaviour of such sparks. Their earlier experimental work was restricted to only one initial pressure, and in this paper they extend the examined pressure range to obtain some general conclusions on the pressure dependence of the spark behaviour.

  12. A Lagrangian-dependent metric space

    International Nuclear Information System (INIS)

    El-Tahir, A.

    1989-08-01

    A generalized Lagrangian-dependent metric of the static isotropic spacetime is derived. Its behaviour should be governed by imposing physical constraints allowing to avert the pathological features of gravity at the strong field domain. This would restrict the choice of the Lagrangian form. (author). 10 refs

  13. Maritime Load Dependent Lead Times - An Analysis

    DEFF Research Database (Denmark)

    Pahl, Julia; Voss, Stefan

    2017-01-01

    in production. Inspired by supply chain planning systems, we analyze the current state of (collaborative) planning in the maritime transport chain with focus on containers. Regarding the problem of congestion, we particularly emphasize on load dependent lead times (LDLT) which are well studied in production....

  14. Environmentally dependent bond-order potentials: New ...

    Indian Academy of Sciences (India)

    Environmentally dependent bond-order potentials: New developments and applications ... for modelling amorphous structure we found that the and bond integrals are not only transferable between graphite and diamond structures but they are also strongly anisotropic due to inter-plan bonding between graphite sheets.

  15. Smartphone dependence classification using tensor factorization.

    Directory of Open Access Journals (Sweden)

    Jingyun Choi

    Full Text Available Excessive smartphone use causes personal and social problems. To address this issue, we sought to derive usage patterns that were directly correlated with smartphone dependence based on usage data. This study attempted to classify smartphone dependence using a data-driven prediction algorithm. We developed a mobile application to collect smartphone usage data. A total of 41,683 logs of 48 smartphone users were collected from March 8, 2015, to January 8, 2016. The participants were classified into the control group (SUC or the addiction group (SUD using the Korean Smartphone Addiction Proneness Scale for Adults (S-Scale and a face-to-face offline interview by a psychiatrist and a clinical psychologist (SUC = 23 and SUD = 25. We derived usage patterns using tensor factorization and found the following six optimal usage patterns: 1 social networking services (SNS during daytime, 2 web surfing, 3 SNS at night, 4 mobile shopping, 5 entertainment, and 6 gaming at night. The membership vectors of the six patterns obtained a significantly better prediction performance than the raw data. For all patterns, the usage times of the SUD were much longer than those of the SUC. From our findings, we concluded that usage patterns and membership vectors were effective tools to assess and predict smartphone dependence and could provide an intervention guideline to predict and treat smartphone dependence based on usage data.

  16. Smartphone dependence classification using tensor factorization.

    Science.gov (United States)

    Choi, Jingyun; Rho, Mi Jung; Kim, Yejin; Yook, In Hye; Yu, Hwanjo; Kim, Dai-Jin; Choi, In Young

    2017-01-01

    Excessive smartphone use causes personal and social problems. To address this issue, we sought to derive usage patterns that were directly correlated with smartphone dependence based on usage data. This study attempted to classify smartphone dependence using a data-driven prediction algorithm. We developed a mobile application to collect smartphone usage data. A total of 41,683 logs of 48 smartphone users were collected from March 8, 2015, to January 8, 2016. The participants were classified into the control group (SUC) or the addiction group (SUD) using the Korean Smartphone Addiction Proneness Scale for Adults (S-Scale) and a face-to-face offline interview by a psychiatrist and a clinical psychologist (SUC = 23 and SUD = 25). We derived usage patterns using tensor factorization and found the following six optimal usage patterns: 1) social networking services (SNS) during daytime, 2) web surfing, 3) SNS at night, 4) mobile shopping, 5) entertainment, and 6) gaming at night. The membership vectors of the six patterns obtained a significantly better prediction performance than the raw data. For all patterns, the usage times of the SUD were much longer than those of the SUC. From our findings, we concluded that usage patterns and membership vectors were effective tools to assess and predict smartphone dependence and could provide an intervention guideline to predict and treat smartphone dependence based on usage data.

  17. Measurements of temperature dependence of 'localized susceptibility'

    CERN Document Server

    Shiozawa, H; Ishii, H; Takayama, Y; Obu, K; Muro, T; Saitoh, Y; Matsuda, T D; Sugawara, H; Sato, H

    2003-01-01

    The magnetic susceptibility of some rare-earth compounds is estimated by measuring magnetic circular dichroism (MCD) of rare-earth 3d-4f absorption spectra. The temperature dependence of the magnetic susceptibility obtained by the MCD measurement is remarkably different from the bulk susceptibility in most samples, which is attributed to the strong site selectivity of the core MCD measurement.

  18. Scale dependent inference in landscape genetics

    Science.gov (United States)

    Samuel A. Cushman; Erin L. Landguth

    2010-01-01

    Ecological relationships between patterns and processes are highly scale dependent. This paper reports the first formal exploration of how changing scale of research away from the scale of the processes governing gene flow affects the results of landscape genetic analysis. We used an individual-based, spatially explicit simulation model to generate patterns of genetic...

  19. Costs of Oil Dependence: A 2000 Update

    International Nuclear Information System (INIS)

    Greene, D.L.; Tishchishyna, N.I.

    2000-01-01

    Oil dependence remains a potentially serious economic and strategic problem for the United States. This report updates previous estimates of the costs of oil dependence to the U.S. economy and introduces several methodological enhancements. Estimates of the costs to the U.S. economy of the oil market upheavals of the last 30 years are in the vicinity of $7 trillion, present value 1998 dollars, about as large as the sum total of payments on the national debt over the same period. Simply adding up historical costs in 1998 dollars without converting to present value results in a Base Case cost estimate of $3.4 trillion. Sensitivity analysis indicates that cost estimates are sensitive to key parameters. A lower bound estimate of $1.7 trillion and an upper bound of $7.1 trillion (not present value) indicate that the costs of oil dependence have been large under almost any plausible set of assumptions. These cost estimates do not include military, strategic or political costs associated with U.S. and world dependence on oil imports

  20. Including Children Dependent on Ventilators in School.

    Science.gov (United States)

    Levine, Jack M.

    1996-01-01

    Guidelines for including ventilator-dependent children in school are offered, based on experience with six such students at a New York State school. Guidelines stress adherence to the medical management plan, the school-family partnership, roles of the social worker and psychologist, orientation, transportation, classroom issues, and steps toward…