Sample records for ciprofibrate increases cholesteryl

  1. Induction of peroxisome proliferation in rainbow trout exposed to ciprofibrate. (United States)

    Yang, J H; Kostecki, P T; Calabrese, E J; Baldwin, L A


    Rainbow trout (Salmo gairdneri), average body weight of 450 g, were treated with 15, 25, or 35 mg/kg of ciprofibrate via intraperitoneal injection every other day for 2 to 3 weeks. The effects on hepatic peroxisomal acyl-CoA oxidase, polypeptide PPA-80, catalase, and liver weight were measured. The treatment of trout with ciprofibrate showed significant dose-related increases in peroxisomal acyl-CoA activity, polypeptide PPA-80, and catalase after 3 weeks of exposure. Peroxisomal oxidase activity showed a significant (p = 0.0008) increase (78%) at 35 mg/kg and a marginal (p = 0.1) increase (27%) at 25 mg/kg after 3 weeks of exposure. Densitometric analysis of polypeptide PPA-80 and catalase showed increases up to 48 and 236% at 35 mg/kg, respectively. Morphometric analysis on livers of trout administered 35 mg/kg for 3 weeks showed a 2.3-fold increase of peroxisomal volume density, as compared to control. This study demonstrates the induction of peroxisome proliferation in rainbow trout administered ciprofibrate, a known peroxisome proliferator in rodents.

  2. Increased large VLDL particles confer elevated cholesteryl ester transfer in diabetes

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; de Vries, Rindert; Kwakernaak, Arjan J.; Perton, Frank; Dallinga-Thie, Geesje M.


    BackgroundPlasma cholesteryl ester transfer (CET), reflecting transfer of cholesteryl esters from high density lipoproteins (HDL) towards apolipoprotein B-containing lipoproteins, may promote atherosclerosis development, and is elevated in Type 2 diabetes mellitus (T2DM). We determined the extent to

  3. Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. (United States)

    Maes, M; Smith, R; Christophe, A; Cosyns, P; Desnyder, R; Meltzer, H


    Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and omega 3 essential fatty acid levels and by an increased C20: 4 omega 6/C20: 5 omega 3, i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2, C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of omega 6 and omega 3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios omega 6/omega 3 and C20:4 omega 6/C20:5 omega 3 were calculated. Major depressed subjects had significantly higher C20:4 omega 6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased omega 6/omega 3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3 omega 3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total omega 3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5 omega 3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.

  4. The peroxisome proliferator-activated receptor alpha-selective activator ciprofibrate upregulates expression of genes encoding fatty acid oxidation and ketogenesis enzymes in rat brain. (United States)

    Cullingford, Tim E; Dolphin, Colin T; Sato, Hitoshi


    Activated peroxisome proliferator activated receptor alpha (PPAR alpha) protects against the cellular inflammatory response, and is central to fatty acid-mediated upregulation of the gene encoding the key ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS). We have previously demonstrated both PPAR alpha and mHS expression in brain, implying that brain-targeted PPAR alpha activators may likewise up-regulate mHS expression in brain. Thus, to attempt pharmacological activation of brain PPAR alpha in vivo, we have administered to rats two drugs with previously defined actions in rat brain, namely the PPAR alpha-selective activator ciprofibrate and the pan-PPAR activator valproate. Using the sensitive and discriminatory RNase protection co-assay, we demonstrate that both ciprofibrate and valproate induce mHS expression in liver, the archetypal PPAR alpha-expressing organ. Furthermore, ciprofibrate potently increases mHS mRNA abundance in rat brain, together with lesser increases in two other PPAR alpha-regulated mRNAs. Thus we demonstrate, for the first time, up-regulation of expression of PPAR alpha-dependent genes including mHS in brain, with implications in the increased elimination of neuro-inflammatory lipids and concomitant increased production of neuro-protective ketone bodies.

  5. Modification of composition of a nanoemulsion with different cholesteryl ester molecular species: Effects on stability, peroxidation, and cell uptake

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    Cristina P Almeida


    Full Text Available Cristina P Almeida1, Carolina G Vital1, Thais C Contente1, Durvanei A Maria2, Raul C Maranhão1,31Lipid Metabolism Laboratory, Heart Institute (InCor, Medical School Hospital, 2Biochemistry and Biophysics Laboratories, Butantan Institute, 3Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, BrazilPurpose: Use of lipid nanoemulsions as carriers of drugs for therapeutic or diagnostic purposes has been increasingly studied. Here, it was tested whether modifications of core particle constitution could affect the characteristics and biologic properties of lipid nanoemulsions. Methods: Three nanoemulsions were prepared using cholesteryl oleate, cholesteryl stearate, or cholesteryl linoleate as main core constituents. Particle size, stability, pH, peroxidation of the nanoemulsions, and cell survival and uptake by different cell lines were evaluated.Results: It was shown that cholesteryl stearate nanoemulsions had the greatest particle size and all three nanoemulsions were stable during the 237-day observation period. The pH of the three nanoemulsion preparations tended to decrease over time, but the decrease in pH of cholesteryl stearate was smaller than that of cholesteryl oleate and cholesteryl linoleate. Lipoperoxidation was greater in cholesteryl linoleate than in cholesteryl oleate and cholesteryl stearate. After four hours’ incubation of human umbilical vein endothelial cells (HUVEC with nanoemulsions, peroxidation was minimal in the presence of cholesteryl oleate and more pronounced with cholesteryl linoleate and cholesteryl stearate. In contrast, macrophage incubates showed the highest peroxidation rates with cholesteryl oleate. Cholesteryl linoleate induced the highest cell peroxidation rates, except in macrophages. Uptake of cholesteryl oleate nanoemulsion by HUVEC and fibroblasts was greater than that of cholesteryl linoleate and cholesteryl stearate. Uptake of the three nanoemulsions by monocytes was equal. Uptake of

  6. Elevated cholesteryl ester transfer protein concentration is associated with an increased risk for cardiovascular disease in women, but not in men, with Type 2 diabetes : the Hoorn Study

    NARCIS (Netherlands)

    Alssema, M; Dekker, J M; Kuivenhoven, J A; Nijpels, G; Teerlink, T; Scheffer, P G; Diamant, M; Stehouwer, C D A; Bouter, L M; Heine, R J


    AIMS: Cholesteryl ester transfer protein (CETP) exchanges neutral lipids between lipoproteins. As the role of CETP in the atherogenic process is still not fully clarified, we studied the association of CETP concentration with the prevalence of cardiovascular disease (CVD) and with intima-media thick

  7. Synthesis of Hypolipidemic Ciprofibrate%降血脂药环丙贝特的合成

    Institute of Scientific and Technical Information of China (English)

    雷继中; 赵建强; 刘斌; 周鸣强


    A new approach for the synthesis of hypolipidemic ciprofibrate was reported. Ciprofibrate with an overall yield of 69. 4% and purity up to 99. 7% was obtained via Witting reaction, etherifica-tion, cyclization and hydrolysis using 4-hydroxybenzaldehyde as the starting material. The structure was confirmed by 1 H NMR, 13 C NMR and HR-MS( ESI) .%报道了一种合成降血脂药物环丙贝特的新工艺。以对羟基苯甲醛为原料,经Witting反应、醚化、环化及水解共4步反应合成了环丙贝特,总收率69.4%,纯度99.7%,其结构经1H NMR,13C NMR和HR-MS(ESI)确证。

  8. Validation of a spectrophotometric method to determine ciprofibrate content in tablets

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    Guilherme Nobre Lima do Nascimento


    Full Text Available Ciprofibrate is a drug indicated in cases of hypertriglyceridemia and mixed hyperlipidemia, but no monographs are available in official compendia for the analysis of this substance in tablets. The objective of this work was to develop and validate a spectrophotometric method for routine analysis of ciprofibrate in tablets. In this study, commercial and standard ciprofibrate were used, as well as placebo in absolute ethanol, analyzed by UV spectrophotometer. All tests followed the rules of Resolution RE-899, 2003. The results showed that the developed and validated method offers low cost, easy implementation, precision and accuracy, and may be included in the routine of quality control laboratories.O ciprofibrato é um fármaco indicado em casos de hipertrigliceridemia e hiperlipidemia mista, mas não há monografias em compêndios oficiais para a análise desta substância em comprimidos. O objetivo deste trabalho é desenvolver e validar um método espectrofotométrico para análise de rotina de ciprofibrato em comprimidos. Neste estudo foram empregados ciprofibrato comercial, padrão e placebo em etanol absoluto, analisadas por espectrofotometria UV. Todos os testes seguiram as regras da Resolução RE- 899, 2003. Os resultados mostraram que o método desenvolvido e validado apresenta baixo custo, fácil implementação, precisão e exatidão e pode ser incluído em rotina de laboratórios de controle de qualidade.

  9. Lipid Exchange Mechanism of the Cholesteryl Ester Transfer Protein Clarified by Atomistic and Coarse-grained Simulations

    DEFF Research Database (Denmark)

    Koivuniemi, A.; Vuorela, T.; Kovanen, P. T.


    Cholesteryl ester transfer protein (CETP) transports cholesteryl esters, triglycerides, and phospholipids between different lipoprotein fractions in blood plasma. The inhibition of CETP has been shown to be a sound strategy to prevent and treat the development of coronary heart disease. We employed...... change of helix X of CETP to an open state, in which we found the accessibility of cholesteryl esters to the C-terminal tunnel opening of CETP to increase. Furthermore, in the absence of helix X, cholesteryl esters rapidly diffused into CETP through the C-terminal opening. The results provide compelling...

  10. Cholesteryl esters in human malignant neoplasms. (United States)

    Tosi, M R; Bottura, G; Lucchi, P; Reggiani, A; Trinchero, A; Tugnoli, V


    Cholesteryl esters (CholE) were detected in human malignant neoplasms by means of in vitro nuclear magnetic resonance spectroscopy. Spectroscopic analysis of the total lipid extracts obtained from cerebral tumors revealed appreciable amount of esterified cholesterol in high grade gliomas such as glioblastomas and anaplastic oligodendrogliomas, characterized by prominent neovascularity. The finding that no CholE were detected in the healthy brain and in low grade and benign tumors supports a possible correlation between this class of lipids and histological vascular proliferation. Compared with high grade gliomas, renal cell carcinomas show higher levels of CholE, absent in the healthy renal parenchyma and in benign oncocytomas. In nefro-carcinomas, cytoplasmic lipid inclusions and prominent vascularization contribute to the increased levels of CholE present mainly as oleate. CholE are discussed as potential biochemical markers of cancer and as a target for new therapeutic strategies.

  11. An increased coronary risk is paradoxically associated with common cholesteryl ester transfer protein gene variations that relate to higher high-density lipoprotein cholesterol: A population-based study

    NARCIS (Netherlands)

    S.E. Borggreve (Susanna); H.L. Hillege (Hans); B.H.R. Wolffenbuttel (Bruce); P. de Jong (Paul); M.W. Zuurman (Mike); G. van der Steege (Gerrit); A. van Tol (Arie); R.P.F. Dullaart (Robin)


    textabstractBackground: Several cholesteryl ester transfer protein (CETP) polymorphisms affect high-density lipoprotein (HDL) cholesterol, but the impact of CETP gene variants on incident coronary disease in the general population is uncertain after correction for their effect on HDL cholesterol. De

  12. Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice

    NARCIS (Netherlands)

    Hoorn, J.W.A. van der; Haan, W. de; Berbée, J.P.P.; Havekes, L.M.; Jukema, J.W.; Rensen, P.C.; Princen, H.M.G.


    Objective - Niacin potently decreases plasma triglycerides and LDL-cholesterol. In addition, niacin is the most potent HDL-cholesterol- increasing drug used in the clinic. In the present study, we aimed at elucidation of the mechanism underlying its HDL-raising effect. Methods and Results - InAPOE*3

  13. Effects of ethanol, acetaldehyde and cholesteryl esters on pancreatic lysosomes.


    Wilson, J S; Apte, M V; Thomas, M. C.; Haber, P S; Pirola, R C


    Recent studies indicate that altered lysosomal function may be involved in the early stages of pancreatic injury. Chronic consumption of ethanol increases rat pancreatic lysosomal fragility. The aim of this study is to determine whether the lysosomal fragility observed after chronic ethanol consumption is mediated by ethanol per se, its oxidative metabolite acetaldehyde or cholesteryl esters (substances which accumulate in the pancreas after ethanol consumption). Pancreatic lysosomes from cho...

  14. Phase behavior and crystalline structures of cholesteryl ester mixtures: a C-13 MASNMR study. (United States)

    Guo, W; Hamilton, J A


    Cholesteryl esters are a transport and storage form of cholesterol in normal physiology but also a significant lipid in atherosclerotic plaques. To understand better the molecular properties of cholesteryl esters in tissues and plaques, we have studied the polymorphic and mesomorphic features of pure and mixed cholesteryl esters by solid state C-13 NMR with magic angle sample spinning (MASNMR). The temperature-dependent properties of two single components (cholesteryl linoleate (CL, C18:2) and cholesteryl linolenate (CLL, C18:3)), four binary systems (cholesteryl palmitate (CP, C16:0) with CL, CLL or cholesteryl oleate (CO, C18:1), and CO/CL), one ternary system (CO/CP/CL), and one quaternary system (CO/CP/CL/CLL) were studied. The mixing ratios were based on the composition of an atherosclerosis plaque dissected from a cholesterol-fed New Zealand white rabbit. C-13 MASNMR determined the phase transition temperatures, identified the phases present in all systems, and provided novel information about molecular structures. For example, solid CL exhibited a disordered structure with multiple molecular conformations, whereas pure CLL had a crystalline structure different from the three most commonly characterized forms (MLII, MLI, BL). In binary mixtures, the crystalline structure of each cholesteryl ester species was identified by its own characteristic resonances. It was found that CP always existed in its native BL form, but CL and CO were influenced by the composition of the mixture. CL was induced to form MLII crystals by the coexisting CP (55 wt%). When CO was cooled from the isotropic phase, it existed as a mixture of MLII and an amorphous form. The presence of CP significantly accelerated the conversion of the amorphous form to the MLII form. For the ternary mixture co-dried from chloroform, CL cocrystallized with CO in the MLII form and CP existed in BL form. Addition of a small amount of CLL slightly increased the heterogeneity of the solid mixture, but had

  15. Stability-indicating liquid chromatographic and UV spectrophotometric methods for the quantification of ciprofibrate in capsules and tablets

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    Fernanda Macke Hellwig


    Full Text Available This study describes the development and evaluation of stability-indicating liquid chromatographic (LC and UV spectrophotometric methods for the quantification of ciprofibrate (CPF in tablets and capsules. Isocratic LC separation was achieved on a RP18 column using a mobile phase of o-phosphoric acid (0.1% v/v, adjusted to pH 3.0 with triethylamine (10% v/v and acetonitrile (35:65 v/v, with a flow rate of 1.0 mL min-1. Detection was achieved with a photodiode array detector at 233 nm. For the spectrophotometric analysis, ethanol and water were used as the solvent and a wavelength of 233 nm was selected for the detection. The methods were validated according to International Conference on Harmonization (ICH guidelines for validating analytical procedures. Statistical analysis showed no significant difference between the results obtained by the two methods. The proposed methods were successfully applied to the CPF quality-control analysis of tablets and capsules.

  16. How Well Does BODIPY-Cholesteryl Ester Mimic Unlabeled Cholesteryl Esters in High Density Lipoprotein Particles?

    DEFF Research Database (Denmark)

    Karilainen, Topi; Vuorela, Timo; Vattulainen, Ilpo


    We compare the behavior of unlabeled and BODIPY-labeled cholesteryl ester (CE) in high density lipoprotein by atomistic molecular dynamics simulations. We find through replica exchange umbrella sampling and unbiased molecular dynamics simulations that BODIPY labeling has no significant effect...

  17. Phagocytosis of cholesteryl ester is amplified in diabetic mouse macrophages and is largely mediated by CD36 and SR-A.

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    Christopher B Guest

    Full Text Available Type 2 diabetes (T2D is associated with accelerated atherosclerosis, which accounts for approximately 75% of all diabetes-related deaths. Here we investigate the link between diabetes and macrophage cholesteryl ester accumulation. When diabetic (db/db mice are given cholesteryl ester intraperitoneally (IP, peritoneal macrophages (PerMPhis recovered from these animals showed a 58% increase in intracellular cholesteryl ester accumulation over PerMPhis from heterozygote control (db/+ mice. Notably, PerMPhi fluid-phase endocytosis and large particle phagocytosis was equivalent in db/+and db/db mice. However, IP administration of CD36 and SR-A blocking antibodies led to 37% and 25% reductions in cholesteryl ester accumulation in PerMPhi. Finally, in order to determine if these scavenger receptors (SRs were part of the mechanism responsible for the increased accumulation of cholesteryl esters observed in the diabetic mouse macrophages, receptor expression was quantified by flow cytometry. Importantly, db/db PerMPhis showed a 43% increase in CD36 expression and an 80% increase in SR-A expression. Taken together, these data indicate that direct cholesteryl ester accumulation in mouse macrophages is mediated by CD36 and SR-A, and the magnitude of accumulation is increased in db/db macrophages due to increased scavenger receptor expression.

  18. Ciprofibrate therapy in patients with hypertriglyceridemia and low high density lipoprotein (HDL-cholesterol: greater reduction of non-HDL cholesterol in subjects with excess body weight (The CIPROAMLAT study

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    Medel Octavio


    Full Text Available Abstract Background Hypertriglyceridemia in combination with low HDL cholesterol levels is a risk factor for cardiovascular disease. Our objective was to evaluate the efficacy of ciprofibrate for the treatment of this form of dyslipidemia and to identify factors associated with better treatment response. Methods Multicenter, international, open-label study. Four hundred and thirty seven patients were included. The plasma lipid levels at inclusion were fasting triglyceride concentrations between 1.6–3.9 mM/l and HDL cholesterol ≤ 1.05 mM/l for women and ≤ 0.9 mM/l for men. The LDL cholesterol was below 4.2 mM/l. All patients received ciprofibrate 100 mg/d. Efficacy and safety parameters were assessed at baseline and at the end of the treatment. The primary efficacy parameter of the study was percentage change in triglycerides from baseline. Results After 4 months, plasma triglyceride concentrations were decreased by 44% (p 2 compared to the rest of the population (8.2 vs 19.7%, p Conclusions Ciprofibrate is efficacious for the correction of hypertriglyceridemia / low HDL cholesterol. A greater decrease in non-HDL cholesterol was found among cases with excess body weight. The mechanism of action of ciprofibrate may be influenced by the pathophysiology of the disorder being treated.

  19. Facile synthesis and characterization of novel thermo-chromism cholesteryl-containing hydrogen-bonded liquid crystals

    Institute of Scientific and Technical Information of China (English)

    Wan Li He; Tao Liu; Zhou Yang; Dong Yu Zhao; Wei Huang; Hui Cao; Guo Jie Wang; Huai Yang


    Two series of novel cholesteryl-containing H-bonded liquid crystals were prepared through facile self-assembly between cholesteryl isonicotinate (proton acceptor) exhibiting a monotropic cholesteric phase, and the 4-alkoxy-benzoic acid or 4-alkoxy cinnamic acid (proton donor). It was found that the increase of the conjugate length as well as the terminal length can contribute to enhance the interaction of molecules and thus significantly influenced the thermal behaviors of H-bonded LCs. The cholesteric reflection spectra of the induced mesogenic complexes were located in the visible region with the color tuneable thermo-sensitivity, which could be used for display application.

  20. Helicobacter pylori cholesteryl α-glucosides contribute to its pathogenicity and immune response by natural killer T cells.

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    Yuki Ito

    Full Text Available Approximately 10-15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer, while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT, which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides were recognized by invariant natural killer T (iNKT cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active αCgT into iNKT cell-deficient (Jα18(-/- or wild-type mice, bacterial recovery significantly increased in Jα18(-/- compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18(-/- compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis.

  1. Helicobacter pylori Cholesteryl α-Glucosides Contribute to Its Pathogenicity and Immune Response by Natural Killer T Cells (United States)

    Ito, Yuki; Vela, Jose Luis; Matsumura, Fumiko; Hoshino, Hitomi; Tyznik, Aaron; Lee, Heeseob; Girardi, Enrico; Zajonc, Dirk M.; Liddington, Robert; Kobayashi, Motohiro; Bao, Xingfeng; Bugaytsova, Jeanna; Borén, Thomas; Jin, Rongsheng; Zong, Yinong; Seeberger, Peter H.; Nakayama, Jun; Kronenberg, Mitchell; Fukuda, Minoru


    Approximately 10–15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer), while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT), which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides were recognized by invariant natural killer T (iNKT) cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active αCgT into iNKT cell-deficient (Jα18−/−) or wild-type mice, bacterial recovery significantly increased in Jα18−/− compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18−/− compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis. PMID:24312443

  2. High plasma cholesteryl ester transfer protein levels may favour reduced incidence of cardiovascular events in men with low triglycerides

    NARCIS (Netherlands)

    Borggreve, Susanna E.; Hillege, Hans L.; Dallinga-Thie, Geesje M.; de Jong, Paul E.; Wolffenbuttel, Bruce H. R.; Grobbee, Diederik E.; van Tol, Arie; Dullaart, Robin P. F.


    Aims High cholesteryl ester transfer protein (CETP) concentrations are associated with increased risk of cardiovascular disease (CVD) in subjects with high triglycerides. We determined the relationship of plasma CETP with incident CVD in a population with relatively low triglycerides. Methods and re

  3. Separating the Mechanism-Based and Off-Target Actions of Cholesteryl Ester Transfer Protein Inhibitors With CETP Gene Polymorphisms

    NARCIS (Netherlands)

    Sofat, Reecha; Hingorani, Aroon D.; Smeeth, Liam; Humphries, Steve E.; Talmud, Philippa J.; Cooper, Jackie; Shah, Tina; Sandhu, Manjinder S.; Ricketts, Sally L.; Boekholdt, S. Matthijs; Wareham, Nicholas; Khaw, Kay Tee; Kumari, Meena; Kivimaki, Mika; Marmot, Michael; Asselbergs, Folkert W.; van der Harst, Pim; Dullaart, Robin P. F.; Navis, Gerjan; van Veldhuisen, Dirk J.; Van Gilst, Wiek H.; Thompson, John F.; McCaskie, Pamela; Palmer, Lyle J.; Arca, Marcello; Quagliarini, Fabiana; Gaudio, Carlo; Cambien, Francois; Nicaud, Viviane; Poirer, Odette; Gudnason, Vilmundur; Isaacs, Aaron; Witteman, Jacqueline C. M.; van Duijn, Cornelia M.; Pencina, Michael; Vasan, Ramachandran S.; D'Agostino, Ralph B.; Ordovas, Jose; Li, Tricia Y.; Kakko, Sakari; Kauma, Heikki; Savolainen, Markku J.; Kesaniemi, Y. Antero; Sandhofer, Anton; Paulweber, Bernhard; Sorli, Jose V.; Goto, Akimoto; Yokoyama, Shinji; Okumura, Kenji; Horne, Benjamin D.; Packard, Chris; Freeman, Dilys; Ford, Ian; Sattar, Naveed; McCormack, Valerie; Lawlor, Debbie A.; Ebrahim, Shah; Smith, George Davey; Kastelein, John J. P.; Deanfield, John; Casas, Juan P.


    Background-Cholesteryl ester transfer protein (CETP) inhibitors raise high-density lipoprotein (HDL) cholesterol, but torcetrapib, the first-in-class inhibitor tested in a large outcome trial, caused an unexpected blood pressure elevation and increased cardiovascular events. Whether the hypertensive

  4. Separating the mechanism-based and off-target actions of cholesteryl ester transfer protein inhibitors with CETP gene polymorphisms

    NARCIS (Netherlands)

    R. Sofat (Reecha); A. Hingorani (Aroon); L. Smeeth (Liam); S.E. Humphries (Steve); P.J. Talmud; J. Cooper (Jim); T. Shah (Tina); M.S. Sandhu (Manjinder); S.L. Ricketts (Sally); S.M. Boekholdt (Matthijs); N.J. Wareham (Nick); K-T. Khaw (Kay-Tee); M. Kumari (Meena); M. Kivimaki (Mika); M. Marmot (Michael); F.W. Asselbergs (Folkert); P. van der Harst (Pim); R.P.F. Dullaart (Robin); G. Navis (Gerjan); D.J. van Veldhuisen (Dirk); W.H. van Gilst (Wiek); J.F. Thompson (John); P. McCaskie (Pamela); C. Palmer (Cameron); M. Arca (Marcello); F. Quagliarini (Fabiana); C. Gaudio (Carlo); F. Cambien (François); V. Nicaud; O. Poirer (Odette); V. Gudnason (Vilmundur); A.J. Isaacs (Aaron); J.C.M. Witteman (Jacqueline); P. Tikka-Kleemola (Päivi); M. Pencina (Michael); R.S. Vasan (Ramachandran Srini); R.B. D'Agostino (Ralph); J.M. Ordovas (Jose); T.Y. Li (Tricia); S. Kakko (Sakari); H. Kauma (Heikki); M.J. Savolainen (Markku); Y.A. Kesäniemi (Antero); A. Sandhofer (Anton); B. Paulweber (Bernhard); J.V. Sorli (Jose); A. Goto (Akimoto); S. Yokoyama (Shinji); K. Okumura (Kenji); B.D. Horne (Benjamin); C. Packard (Chris); D. Freeman (Dilys); I. Ford (Ian); N. Sattar (Naveed); V. McCormack (Valerie); D.A. Lawlor (Debbie); S. Ebrahim (Shanil); G.D. Smith; J.J.P. Kastelein (John); J. Deanfield (John); J.P. Casas (Juan)


    textabstractBackground: Cholesteryl ester transfer protein (CETP) inhibitors raise high-density lipoprotein (HDL) cholesterol, but torcetrapib, the first-in-class inhibitor tested in a large outcome trial, caused an unexpected blood pressure elevation and increased cardiovascular events. Whether the

  5. Lipid exchange mechanism of the cholesteryl ester transfer protein clarified by atomistic and coarse-grained simulations.

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    Artturi Koivuniemi


    Full Text Available Cholesteryl ester transfer protein (CETP transports cholesteryl esters, triglycerides, and phospholipids between different lipoprotein fractions in blood plasma. The inhibition of CETP has been shown to be a sound strategy to prevent and treat the development of coronary heart disease. We employed molecular dynamics simulations to unravel the mechanisms associated with the CETP-mediated lipid exchange. To this end we used both atomistic and coarse-grained models whose results were consistent with each other. We found CETP to bind to the surface of high density lipoprotein (HDL -like lipid droplets through its charged and tryptophan residues. Upon binding, CETP rapidly (in about 10 ns induced the formation of a small hydrophobic patch to the phospholipid surface of the droplet, opening a route from the core of the lipid droplet to the binding pocket of CETP. This was followed by a conformational change of helix X of CETP to an open state, in which we found the accessibility of cholesteryl esters to the C-terminal tunnel opening of CETP to increase. Furthermore, in the absence of helix X, cholesteryl esters rapidly diffused into CETP through the C-terminal opening. The results provide compelling evidence that helix X acts as a lid which conducts lipid exchange by alternating the open and closed states. The findings have potential for the design of novel molecular agents to inhibit the activity of CETP.

  6. Critical role of neutral cholesteryl ester hydrolase 1 in cholesteryl ester hydrolysis in murine macrophages[S (United States)

    Sakai, Kent; Igarashi, Masaki; Yamamuro, Daisuke; Ohshiro, Taichi; Nagashima, Shuichi; Takahashi, Manabu; Enkhtuvshin, Bolormaa; Sekiya, Motohiro; Okazaki, Hiroaki; Osuga, Jun-ichi; Ishibashi, Shun


    Hydrolysis of intracellular cholesteryl ester (CE) is the rate-limiting step in the efflux of cholesterol from macrophage foam cells. In mouse peritoneal macrophages (MPMs), this process is thought to involve several enzymes: hormone-sensitive lipase (Lipe), carboxylesterase 3 (Ces3), neutral CE hydrolase 1 (Nceh1). However, there is some disagreement over the relative contributions of these enzymes. To solve this problem, we first compared the abilities of several compounds to inhibit the hydrolysis of CE in cells overexpressing Lipe, Ces3, or Nceh1. Cells overexpressing Ces3 had negligible neutral CE hydrolase activity. We next examined the effects of these inhibitors on the hydrolysis of CE and subsequent cholesterol trafficking in MPMs. CE accumulation was increased by a selective inhibitor of Nceh1, paraoxon, and two nonselective inhibitors of Nceh1, (+)-AS115 and (−)-AS115, but not by two Lipe-selective inhibitors, orlistat and 76-0079. Paraoxon inhibited cholesterol efflux to apoA-I or HDL, while 76-0079 did not. These results suggest that Nceh1 plays a dominant role over Lipe in the hydrolysis of CE and subsequent cholesterol efflux in MPMs. PMID:24868095


    NARCIS (Netherlands)



    The activity of cholesteryl ester transfer protein is instrumental in the distribution of cholesteryl ester between lipoproteins in plasma. We measured the activity of cholesteryl ester transfer protein in plasma, designated cholesteryl ester transfer activity, as the rate of cholesteryl ester trans

  8. Renin-angiotensin-aldosterone responsiveness to low sodium and blood pressure reactivity to angiotensin-II are unrelated to cholesteryl ester transfer protein mass in healthy subjects

    NARCIS (Netherlands)

    Krikken, Jan A.; Dallinga-Thie, Geesje M.; Navis, Gerjan; Dullaart, Robin P. F.


    Background: The blood pressure increase associated with the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib is probably attributable to an off-target effect but it is unknown whether activation of the renin-angiotensin-aldosterone system (RAAS) may be related to variation in the pla

  9. Antiproteinuric therapy decreases LDL-cholesterol as well as HDL-cholesterol in non-diabetic proteinuric patients: relationships with cholesteryl ester transfer protein mass and adiponectin

    NARCIS (Netherlands)

    J.A. Krikken; F. Waanders; G.M. Dallinga-Thie; L.D. Dikkeschei; L. Vogt; G.J. Navis; R.P.F. Dullaart


    Objective: Dyslipidemia contributes to increased cardiovascular risk in nephrotic syndrome. We questioned whether reduction in proteinuria not only lowers low-density lipoprotein cholesterol (LDL-C), but also high-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP)

  10. Antiproteinuric therapy decreases LDL-cholesterol as well as HDL-cholesterol in non-diabetic proteinuric patients : relationships with cholesteryl ester transfer protein mass and adiponectin

    NARCIS (Netherlands)

    Krikken, J. A.; Waanders, F.; Dallinga-Thie, G. M.; Dikkeschei, L. D.; Vogt, L.; Navis, G. J.; Dullaart, R. P. F.


    Objective: Dyslipidemia contributes to increased cardiovascular risk in nephrotic syndrome. We questioned whether reduction in proteinuria not only lowers low-density lipoprotein cholesterol (LDL-C), but also high-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP)

  11. Entamoeba mitosomes play an important role in encystation by association with cholesteryl sulfate synthesis. (United States)

    Mi-ichi, Fumika; Miyamoto, Tomofumi; Takao, Shouko; Jeelani, Ghulam; Hashimoto, Tetsuo; Hara, Hiromitsu; Nozaki, Tomoyoshi; Yoshida, Hiroki


    Hydrogenosomes and mitosomes are mitochondrion-related organelles (MROs) that have highly reduced and divergent functions in anaerobic/microaerophilic eukaryotes. Entamoeba histolytica, a microaerophilic, parasitic amoebozoan species, which causes intestinal and extraintestinal amoebiasis in humans, possesses mitosomes, the existence and biological functions of which have been a longstanding enigma in the evolution of mitochondria. We previously demonstrated that sulfate activation, which is not generally compartmentalized to mitochondria, is a major function of E. histolytica mitosomes. However, because the final metabolites of sulfate activation remain unknown, the overall scheme of this metabolism and the role of mitosomes in Entamoeba have not been elucidated. In this study we purified and identified cholesteryl sulfate (CS) as a final metabolite of sulfate activation. We then identified the gene encoding the cholesteryl sulfotransferase responsible for synthesizing CS. Addition of CS to culture media increased the number of cysts, the dormant form that differentiates from proliferative trophozoites. Conversely, chlorate, a selective inhibitor of the first enzyme in the sulfate-activation pathway, inhibited cyst formation in a dose-dependent manner. These results indicate that CS plays an important role in differentiation, an essential process for the transmission of Entamoeba between hosts. Furthermore, we show that Mastigamoeba balamuthi, an anaerobic, free-living amoebozoan species, which is a close relative of E. histolytica, also has the sulfate-activation pathway in MROs but does not possess the capacity for CS production. Hence, we propose that a unique function of MROs in Entamoeba contributes to its adaptation to its parasitic life cycle.

  12. Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains

    Directory of Open Access Journals (Sweden)

    Di Bari Michele A


    Full Text Available Abstract Objective Cholesterol changes have been described in prion-cell models and in experimental rodent scrapie; yet, the pattern of this association is still controversial. Methods To shed light on the matter, we analysed and compared cholesterol variations in ScN2a cells and in brains of Scrapie-infected C57Bl/6 mice, using two different methods: a fluorimetric-enzymatic cholesterol assay, and high performance liquid chromatography-mass spectroscopy (HPLC-MS. Results Compared to uninfected controls, similar cholesterol metabolism anomalies were observed in infected cells and brains by both methods; however, only HPLC-MS revealed statistically significant cholesterol variations, particularly in the cholesteryl esters (CE fraction. HPLC-MS analyses also revealed different fatty acid composition of the CE fraction in cells and brains. In N2a cells, their profile reflected that of serum, while in normal brains cholesteryl-linoleate only was found at detectable levels. Following prion infection, most CE species were increased in the CE pool of ScN2a cells, whereas a conspicuous amount of cholesteryl-arachidonate only was found to contribute to the cerebral increase of CE. Of interest, oral pravastatin administration to Scrapie-infected mice, was associated with a significant reduction of cerebral free cholesterol (FC along with a concomitant further increase of the CE pool, which included increased amounts of both cholesteryl-linoleate and cholesteryl-arachidonate. Conclusion Although mechanistic studies are needed to establish the pathophysiological relevance of changes in cerebral CE concentrations, to the best of our knowledge this is the first report to provide evidence of increased cholesterol esterification in brains of prion-infected mice, untreated and treated with pravastatin.

  13. Lowered omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. (United States)

    Maes, M; Christophe, A; Delanghe, J; Altamura, C; Neels, H; Meltzer, H Y


    Depression is associated with a lowered degree of esterification of serum cholesterol, an increased C20:4omega6/C20:5omega3 ratio and decreases in omega3 fractions in fatty acids (FAs) or in the red blood cell membrane. The aims of the present study were to examine: (i) serum phospholipid and cholesteryl ester compositions of individual saturated fatty acids (SFAs), monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs) in major depressed patients vs. healthy volunteers; (ii) the relationships between the above FAs and lowered serum zinc (Zn), a marker of the inflammatory response in depression; and (iii) the effects of subchronic treatment with antidepressants on FAs in depression. The composition of the FAs was determined by means of thin layer chromatography in conjunction with gas chromatography. Lipid concentrations were assayed by enzymatic colorimetric methods. The oxidative potential index (OPI) of FAs was computed in 34 major depressed inpatients and 14 normal volunteers. Major depression was associated with: increased MUFA and C22:5omega3 proportions and increased C20:4omega6/C20:5omega3 and C22:5omega6/C22:6omega3 ratios; lower C22:4omega6, C20:5omega3 and C22:5omega3 fractions in phospholipids; lower C18:3omega3, C20:5omega3 and total (sigma)omega3 FAs, and higher C20:4omega6/C20:5omega3 and sigmaomega6/sigmaomega3 ratios in cholesteryl esters; lower serum concentrations of phospholipids and cholesteryl esters; and a decreased OPI. In depression, there were significant and positive correlations between serum Zn and C20:5omega3 and C22:6omega3 fractions in phospholipids; and significant inverse correlations between serum Zn and the sigmaomega6/sigmaomega3, C20:4omega6/C20:5omega3, and C22:5omega6/C22:6omega3 ratios in phospholipids. There was no significant effect of antidepressive treatment on any of the FAs. The results show that, in major depression, there is a deficiency of omega3 PUFAs and a compensatory increase in MUFAs and C22:5omega6 in

  14. Elevated plasma cholesteryl ester transfer in NIDDM : relationships with apolipoprotein B-containing lipoproteins and phospholipid transfer protein

    NARCIS (Netherlands)

    Riemens, S; van Tol, A; Sluiter, W; Dullaart, R


    Lecithin:cholesteryl acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of cholesterol and the subsequent transfer of cholesteryl ester from high density lipoproteins (HDL) towards very low and low density lipoproteins (VLDL + LDL). Phospholip

  15. How well does cholesteryl hemisuccinate mimic cholesterol in saturated phospholipid bilayers?

    DEFF Research Database (Denmark)

    Kulig, W.; Tynkkynen, J.; Javanainen, M.


    Cholesteryl hemisuccinate is a detergent that is often used to replace cholesterol in crystallization of membrane proteins. Here we employ atomistic molecular dynamics simulations to characterize how well the properties of cholesteryl hemisuccinate actually match those of cholesterol in saturated...... protein-free lipid membranes. We show that the protonated form of cholesteryl hemisuccinate mimics many of the membrane properties of cholesterol quite well, while the deprotonated form of cholesteryl hemisuccinate is less convincing in this respect. Based on the results, we suggest that cholesteryl...... hemisuccinate in its protonated form is a quite faithful mimic of cholesterol for membrane protein crystallization, if specific cholesterol-protein interactions (not investigated here) are not playing a crucial role....

  16. Mutation of residues 423 (Met/Ile), 444 (Thr/Met), and 506 (Asn/Ser) confer cholesteryl esterase activity on rat lung carboxylesterase. Ser-506 is required for activation by cAMP-dependent protein kinase. (United States)

    Wallace, T J; Kodsi, E M; Langston, T B; Gergis, M R; Grogan, W M


    Site-directed mutagenesis is used to identify amino acid residues that dictate reported differences in substrate specificity between rat hepatic neutral cytosolic cholesteryl ester hydrolase (hncCEH) and rat lung carboxylesterase (LCE), proteins differing by only 4 residues in their primary sequences. Beginning with LCE, the substitution Met(423) --> Ile(423) alone or in combination with other mutations increased activity with p-nitrophenylcaprylate (PNPC) relative to more hydrophilic p-nitrophenylacetate (PNPA), typical of hncCEH. The substitution Thr(444) --> Met(444) was necessary but not sufficient for expression of cholesteryl esterase activity in COS-7 cells. The substitution Asn(506) --> Ser(506), creating a potential phosphorylation site, uniformly increased activity with both PNPA and PNPC, was necessary but not sufficient for expression of cholesteryl esterase activity and conferred susceptibility to activation by cAMP-dependent protein kinase, a property of hncCEH. The 3 mutations in combination were necessary and sufficient for expression of cholesteryl esterase activity by the mutated LCE. The substitution Gln(186) --> Arg(186) selectively reduced esterase activity with PNPA and PNPC but was not required for cholesteryl esterase activity. Homology modeling from x-ray structures of acetylcholinesterases is used to propose three-dimensional models for hncCEH and LCE that provide insight into the effects of these mutations on substrate specificity.

  17. The micromethod for determination of cholesterol, cholesteryl esters and phospholipids

    Directory of Open Access Journals (Sweden)



    Full Text Available We examined the method for determining microquantities of lipids, including cholesterol, cholesteryl esters and phospholipids. A standard colorimetric procedure of cholesteryl esters was modified to accommodate a quantitative thin-layer chromatography. This method involved the following steps. (1 Separation of lipids by a thin-layer chromatography: Lipids were applied to Silica gel G plates. Plates were developed with petroleum ether-diethyl etheracetic acid (82: 18: 2, vIvIv. (2 Elution of cholesterol and its esters from scraped silica gel: After scraping the silica gel with adhered cholesterol and its esters, they were eluted with chloroform-methanol (4: 1, v,tv. In the case of phspholipids, the silica gel was calcified. (3 Colorimetric determination of the lipids: Cholesterol and its esters eluted from the silica gel were determined by the method of ZAK with ROSENTHAL'S color reagent directly and after saponification, respectively. Phospholipids were calculated from the phosphorous content determined by the method of KATES. On the basis of examination of recovery and analyses of lipids extracted from tissue, it was concluded that this method permitted a reliable estimation of microquantities of cholesterol, its esters and phospholipids from small amounts of biological materials.

  18. Xanthohumol, a prenylated chalcone from Humulus lupulus L., inhibits cholesteryl ester transfer protein. (United States)

    Hirata, Hiroshi; Takazumi, Koji; Segawa, Shuichi; Okada, Yukio; Kobayashi, Naoyuki; Shigyo, Tatsuro; Chiba, Hitoshi


    High density lipoprotein (HDL)-cholesterol levels are correlated with a low risk of atherosclerosis. The inhibition of cholesteryl ester transfer protein (CETP), which catalyses cholesterol transfer between lipoproteins, leads to an increase in HDL-cholesterol and is expected to be the next anti-atherogenic target. This study revealed that xanthohumol, a prenylated chalcone, showed the highest inhibition against CETP from screening of natural products in various plants. We investigated the inhibitory activity of some chalcones and flavanones. Naringenin chalcone showed weak CETP inhibition compared with xanthohumol. In addition, isoxanthohumol and naringenin drastically decreased the inhibitory activity. These results suggest that the prenyl group and chalcone structure of xanthohumol were responsible for the CETP inhibitory activity.

  19. Cloning and characterization of cholesteryl ester transfer protein isolated from the tree shrew

    Institute of Scientific and Technical Information of China (English)

    曾武威; 张坚; 陈保生; 吴钢; 薛红


    ObjectiveTo obtain the nucleotide sequence and deduced amino acid sequence of cholesterylester transfer protein (CETP) cDNA from the tree shrew (Tupaia glis). MethodsThe cDNA sequence of the tree shrew CETP was obtained by utilizing the techniqueof switching mechanism at 5' end of RNA transcript (SMART) and rapid amplification of cDNA end (RACE) from the first strand of the cDNA. The amino acidsequence of CETP was deduced from the cDNA sequence and its primary and secondary structures were predicted. ResultsThe sequence of CETP cDNA from tree shrew (GenBank accession number AF334033) covers 1636 bp, including 178 bp at the 3' end of the untranslated region anda 1458 bp fragment in a coding region, which provides the complete sequence of mature tree shrew CETP, although not the initiator methionine. The first 24 bp encodes a partial signal peptide. The mature protein consists of 477 amino acids and is longer than the human version by one amino acid (Gly318). Comparing this amino acid sequence with those of other animals' CETPs, the identity between tree shrew and human and rabbit CETP is 88% and 82%, respectively. The protein is extremely hydrophobic as it contains many hydrophobic residues, especially at the C-terminal, consistent with its function in the transfer of neutral lipids. The amino acid residues concerning with binding and transferringneutral lipids are highly conserved. There is a deletion of an N-linked glycosylation site at Asn342 in the tree shrew CETP protein that may participate in the removal of peripheral cholesterol and cholesteryl ester by increasing its activity of transferring cholesteryl ester. ConclusionThe possible glycosylation in the tree shrew CETP may be involved in the molecular mechanism of its insusceptibility to atherosclerosis.

  20. How anacetrapib inhibits the activity of the cholesteryl ester transfer protein? Perspective through atomistic simulations

    DEFF Research Database (Denmark)

    Aijanen, T.; Koivuniemi, A.; Javanainen, M.


    Cholesteryl ester transfer protein (CETP) mediates the reciprocal transfer of neutral lipids (cholesteryl esters, triglycerides) and phospholipids between different lipoprotein fractions in human blood plasma. A novel molecular agent known as anacetrapib has been shown to inhibit CETP activity...... of anacetrapib turns out to reside in the tunnel inside CETP, near the residues surrounding the N-terminal opening. Free energy calculations show that when anacetrapib resides in this area, it hinders the ability of cholesteryl ester to diffuse out from CETP. The simulations further bring out the ability...

  1. Evolving neural network optimization of cholesteryl ester separation by reversed-phase HPLC


    Jansen, Michael A.; Kiwata, Jacqueline; Arceo, Jennifer; Faull, Kym F.; Hanrahan, Grady; Porter, Edith


    Cholesteryl esters have antimicrobial activity and likely contribute to the innate immunity system. Improved separation techniques are needed to characterize these compounds. In this study, optimization of the reversed-phase high-performance liquid chromatography separation of six analyte standards (four cholesteryl esters plus cholesterol and tri-palmitin) was accomplished by modeling with an artificial neural network–genetic algorithm (ANN-GA) approach. A fractional factorial design was emp...

  2. High-density lipoprotein cholesterol is related to the TaqIB cholesteryl ester transfer protein gene polymorphism and smoking, but not to moderate alcohol consumption in insulin-dependent diabetic men

    NARCIS (Netherlands)

    Dullaart, RPF; Beusekamp, BJ; Riemens, SC; Hoogenberg, K; Stulp, BK; Van Tol, A; Sluiter, WJ


    In non-diabetic subjects, the high-density lipoprotein (HDL) cholesterol level is increased by alcohol and decreased by smoking. The biallelic B1B2 polymorphism of the cholesteryl ester transfer protein (CETP) gene is a genetic determinant of HDL cholesterol. We evaluated the effect of moderate alco

  3. Exploring unsaturated fatty acid cholesteryl esters as transdermal permeation enhancers. (United States)

    Rambharose, Sanjeev; Kalhapure, Rahul S; Jadhav, Mahantesh; Govender, Thirumala


    The intrinsic protective barrier property of skin, one of the major challenges in the design of transdermal drug delivery systems, can be overcome through the use of chemical permeation enhancers (CPEs). Herein, we explore the potential of unsaturated fatty acid (UFA) esters of cholesterol (Chol) viz., oleate, linoleate and linolenate, as transdermal CPEs using tenofovir (TNF) as a model drug. All Chol UFA esters at 1% w/w were found to be more effective enhancers when compared to their respective parent fatty acids (FAs) and saturated FA counterparts. Cholesteryl linolenate (Chol-LLA) showed the most superior performance (enhancement ratio (ER) = 3.71). The greatest ER for Chol-LLA (5.93) was achieved at a concentration of 2% w/w. The histomorphological and transepithelial electrical resistance (TEER) evaluations supported the results of the permeability studies. These findings showed no significant loss in the integrity of the epidermis, with drug and enhancer treatment having temporary effects on the barrier property of the epidermis. Chol UFA esters can therefore be considered as new CPEs for exploitation in topical formulations for various classes of drugs.

  4. Cholesteryl ester transfer protein levels and gene deficiency in Chinese patients with cardio-cerebrovascular diseases

    Institute of Scientific and Technical Information of China (English)

    庄一义; 汪俊军; 张宏娟; 李勇; 刘小传; 李露言; 陈光辉


    Objective To detect cholesteryl ester transfer protein (CETP) levels, frequencies of CETP D442G and Ⅰ14A mutations and characteristics of abnormal lipids in patients with cardio-cerebro vascular diseases. Methods Ninety-four myocardial infarction (MI) patients,110 stroke patients and 335 healthy controls were selected. The CETP concentration was determined using ELISA. The CETP activity was measured using a substrate of 14 C-radiolabeled discoidal bilayer particles. The CETP gene mutations were detected by PCR-RFLP. Results The CETP concentrations in the MI and stroke group, were higher than those in the controls. The gene mutation frequencies of D442G in the MI, stroke and control group were 3.5%, 3.6% and 5%, respectively, and the frequencies of Ⅰ14A were 1.05%, 0.91% and 1%, respectively. One case of D442G homozygote was detected in the healthy group. The frequency of two CETP gene mutations showed no significant difference among the patients and controls. The CETP concentration and activity in subjects with CETP mutations were one-third of those in the control group. The level of HDL-C, apo-A1 increased in the mutation subjects, while the TG level decreased. Conclusions The CETP level increased significantly in patients with cardio-cerebrovascular diseases. The carriers of CETP deficiency had CETP and lipid abnormalities.

  5. Cholesteryl ester transfer protein inhibitors in the treatment of dyslipidemia: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Chuanwei Li

    Full Text Available Cholesteryl ester transfer protein (CETP inhibitors are gaining substantial research interest for raising high density lipoprotein cholesterol levels. The aim of the research was to estimate the efficacy and safety of cholesteryl ester transfer protein inhibitors as novel lipid modifying drugs. Systematic searches of English literature for randomized controlled trials (RCT were collected from MEDLINE, EBASE, CENTRAL and references listed in eligible studies. Two independent authors assessed the search results and only included the double-blind RCTs by using cholesteryl ester transfer protein inhibitors as exclusively or co-administrated with statin therapy irrespective of gender in enrolled adult subjects. Two independent authors extracted the data by using predefined data fields. Of 503 studies identified, 14 studies met the inclusion criteria, and 12 studies were included into the final meta-analysis. Our meta-analysis revealed that CETP inhibitors increased the HDL-c levels (n = 2826, p<0.00001, mean difference (MD = 20.47, 95% CI [19.80 to 21.15] and total cholesterol (n = 3423, p = 0.0002, MD = 3.57, 95%CI [1.69 to 5.44] to some extent combined with a reduction in triglyceride (n = 3739, p<0.00001, MD = -10.47, 95% CI [-11.91 to -9.03] and LDL-c (n = 3159, p<0.00001, MD = -17.12, 95% CI [-18.87 to -15.36] irrespective of mono-therapy or co-administration with statins. Subgroup analysis suggested that the lipid modifying effects varied according to the four currently available CETP inhibitors. CETP inhibitor therapy did not increase the adverse events when compared with control. However, we observed a slight increase in blood pressure (SBP, n = 2384, p<0.00001, MD = 2.73, 95% CI [2.14 to 3.31], DBP, n = 2384, p<0.00001, MD = 1.16, 95% CI [0.73 to 1.60] after CETP inhibitor treatment, which were mainly ascribed to the torcetrapib treatment subgroup. CETP inhibitors therapy is associated with significant increase in HDL-c and decrease in

  6. Novel application of Eudragit RL and cholesteryl oleyl carbonate to thermo-sensitive drug delivery system. (United States)

    Cetin, Emel Oyku; Gundogdu, Evren; Baspinar, Yücel; Karasulu, Ercument; Kirilmaz, Levent


    The Eudragit RL 100 and propylene glycol (PG) membranes with and without cholesteryl oleyl carbonate (COC) were prepared by the solvent casting method to pioneer a novel application of a thermo-sensitive drug delivery system. After that, the properties of these membranes were investigated by thermal, scanning, and porosity studies. Drug permeation studies through all membranes were carried out using salbuthamol sulphate (SBS) at constant temperatures (25°C and 37°C), respectively. The permeability of SBS through the membranes with COC has been shown to be a discontinuous function of temperature, that is, their permeability increased steeply above the phase transition temperature (37°C) of the COC. The thermo-sensitive permeation mechanism for the membranes might be based on the structure change of the membranes caused by the phase transition, so that the membranes could absorb more water. Considering the high biological safety of Eudragit RL 100 and PG membranes with and without COC might be used to develop a novel thermo-sensitive drug delivery system.

  7. Self-assembled monolayers of cholesterol and cholesteryl esters on graphite. (United States)

    Hibino, Masahiro; Tsuchiya, Hiroshi


    The molecular arrangements of self-assembled monolayers (SAMs) of cholesterol, cholesteryl laurate, and cholesteryl stearate adsorbed on a graphite surface were studied using scanning tunneling microscopy (STM) at the liquid-solid interface. The STM images of the SAMs showed two-dimensional periodic arrays of bright regions that corresponded to the sterol rings. However, individual sterol rings could not be observed in the bright regions in the STM images of the cholesterol monolayers. Nevertheless, by comparing the STM images and the crystallographic data, it is concluded that the cholesterol molecules are arranged in pairs oriented head-to-head owing to the hydrogen bonds between the hydroxyl groups. These dimers, in turn, are oriented parallel to each other, owing to the interactions between the sterol rings. The STM images of cholesteryl ester monolayers had molecular resolution and showed pairs of cholesteryl ester molecules oriented in an antiparallel manner, with their fatty acid chains located in the central regions. Furthermore, the fatty acid chains of cholesteryl stearate were observed to be oriented in the (1120) zigzag direction of the graphite lattice, whereas those of cholesteryl laurate were oriented in the (1010) armchair direction. These observations reveal that the interactions between the fatty acid chains affect the structure of the SAMs. The molecular arrangements also depend on the lengths of the fatty acid chains of the cholesterol esters and hence on the interactions between the alkyl chains and the graphite surface. The self-assembly at the liquid-solid interface is therefore controlled by the interactions between sterol rings, between alkyl chains, and between alkyl chains and the substrate.

  8. Enhanced removal from the plasma of LDL-like nanoemulsion cholesteryl ester in trained men compared with sedentary healthy men. (United States)

    Vinagre, Carmen G C; Ficker, Elisabeth S; Finazzo, Claudia; Alves, Maria J N; de Angelis, Katia; Irigoyen, Maria Claudia; Negrão, Carlos E; Maranhão, Raul C


    The objective of this study was to evaluate the effects of exercise training on plasma removal of a cholesterol-rich nanoemulsion (LDE) that mimics low-density lipoprotein (LDL) lipid structure and binds to LDL receptors. LDE-derived cholesteryl ester plasma kinetics was studied in 24 exercise-trained and 20 sedentary male subjects. LDE labeled with [(14)C]cholesteryl ester was injected intravenously, and plasma samples were collected over a 24-h period to determine radioisotope decay curves. LDL cholesterol concentration was similar in both groups. Fractional clearance rate (FCR) of the nanoemulsion label was greater in the exercise-trained group compared with the sedentary group (0.138 +/- 0.152 and 0.0261 +/- 0.023 h(-1), respectively). A positive correlation was found (r = 0.60, P < 0.01) between FCR and peak O(2) consumption in trained subjects. Circulating oxidized LDL levels were lower in trained subjects compared with the sedentary group (9.0 +/- 2.0 and 16.0 +/- 3.0 mU/l). LDE was also injected into control and LDL receptor gene knockout mice submitted and not submitted to training. Muscle LDE uptake percentage was increased in the trained mice compared with the untrained mice (1.1 +/- 0.8 and 0.2 +/- 0.1, respectively, P < 0.0001) in the control group but not in the knockout animals, indicating that the LDL receptor is involved in the increased uptake elicited by exercise. These results show that exercise training increases LDE plasma removal, which in turn suggests that it also increases LDL receptors or LDL receptor activity.

  9. Plasma cholesteryl ester transfer protein is predominantly derived from Kupffer cells

    NARCIS (Netherlands)

    Wang, Y.; Tuin, S. van der; Tjeerdema, N.; Dam, A.D. van; Rensen, S.S.; Hendrikx, T.; Berbee, J.F.; Atanasovska, B.; Fu, J.; Hoekstra, M.; Bekkering, S.; Riksen, N.P.; Buurman, W.A.; Greve, J.W.; Hofker, M.H.; Shiri-Sverdlov, R.; Meijer, O.C.; Smit, J.W.A.; Havekes, L.M.; Dijk, K.W. van; Rensen, P.C.


    The role of Kupffer cells (KCs) in the pathophysiology of the liver has been firmly established. Nevertheless, KCs have been underexplored as a target for diagnosis and treatment of liver diseases owing to the lack of noninvasive diagnostic tests. We addressed the hypothesis that cholesteryl ester t

  10. Plasma Cholesteryl Ester Transfer Protein Is Predominantly Derived From Kupffer Cells

    NARCIS (Netherlands)

    Wang, Yanan; van der Tuin, Sam; Tjeerdema, Nathanja; van Dam, Andrea D.; Rensen, Sander S.; Hendrikx, Tim; Berbee, Jimmy F. P.; Atanasovska, Biljana; Fu, Jingyuan; Hoekstra, Menno; Bekkering, Siroon; Riksen, Niels P.; Buurman, Wim A.; Greve, Jan Willem; Hofker, Marten H.; Shiri-Sverdlov, Ronit; Meijer, Onno C.; Smit, Johannes W. A.; Havekes, Louis M.; van Dijk, Ko Willems; Rensen, Patrick C. N.


    The role of Kupffer cells (KCs) in the pathophysiology of the liver has been firmly established. Nevertheless, KCs have been underexplored as a target for diagnosis and treatment of liver diseases owing to the lack of noninvasive diagnostic tests. We addressed the hypothesis that cholesteryl ester t

  11. Oxidized Cholesteryl Esters and Phospholipids in Zebrafish Larvae Fed a High Cholesterol Diet (United States)

    Fang, Longhou; Harkewicz, Richard; Hartvigsen, Karsten; Wiesner, Philipp; Choi, Soo-Ho; Almazan, Felicidad; Pattison, Jennifer; Deer, Elena; Sayaphupha, Tiffany; Dennis, Edward A.; Witztum, Joseph L.; Tsimikas, Sotirios; Miller, Yury I.


    A novel hypercholesterolemic zebrafish model has been developed to study early events of atherogenesis. This model utilizes optically transparent zebrafish larvae, fed a high cholesterol diet (HCD), to monitor processes of vascular inflammation in live animals. Because lipoprotein oxidation is an important factor in the development of atherosclerosis, in this study, we characterized the oxidized lipid milieu in HCD-fed zebrafish larvae. Using liquid chromatography-mass spectrometry, we show that feeding an HCD for only 2 weeks resulted in up to 70-fold increases in specific oxidized cholesteryl esters, identical to those present in human minimally oxidized LDL and in murine atherosclerotic lesions. The levels of oxidized phospholipids, such as 1-palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphocholine, and of various lysophosphatidylcholines were also significantly elevated. Moreover, lipoproteins isolated from homogenates of HCD-fed larvae induced cell spreading as well as ERK1/2, Akt, and JNK phosphorylation in murine macrophages. Removal of apoB-containing lipoproteins from the zebrafish homogenates with an anti-human LDL antibody, as well as reducing lipid hydroperoxides with ebselen, resulted in inhibition of macrophage activation. The TLR4 deficiency in murine macrophages prevented their activation with zebrafish lipoproteins. Using biotinylated homogenates of HCD-fed larvae, we demonstrated that their components bound to murine macrophages, and this binding was effectively competed by minimally oxidized LDL but not by native LDL. These data provide evidence that molecular lipid determinants of proatherogenic macrophage phenotypes are present in large quantities in hypercholesterolemic zebrafish larvae and support the use of the HCD-fed zebrafish as a valuable model to study early events of atherogenesis. PMID:20710028

  12. The relationship between cholesteryl ester transfer protein levels and risk factor profile in patients with familial hypercholesterolemia

    NARCIS (Netherlands)

    de Grooth, Greetje J; Smilde, Tineke J; Van Wissen, Sanne; Klerkx, Anke H E M; Zwinderman, Aeilko H; Fruchart, Jean-Charles; Kastelein, John J P; Stalenhoef, Anton F H; Kuivenhoven, Jan Albert


    BACKGROUND: Cholesteryl ester transfer protein (CETP) mediates the transfer of neutral lipids between lipoproteins. The role of CETP in atherogenesis is controversial. To better understand the relationships between plasma CETP levels, lipoproteins and atherosclerosis, we assessed these parameters in

  13. Crystallization behavior of supercooled smectic cholesteryl myristate nanoparticles containing phospholipids as stabilizers

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Koch, Michel; Drechsler, M;


    Supercooled smectic nanoparticles based on physiological cholesterol esters are under investigation as a potential novel carrier system for lipophilic drugs. The present study investigates the very complex crystallization behavior of such nanoparticles stabilized with the aid of phospholipids....... Phospholipid and phospholipid/bile salt stabilized cholesteryl myristate dispersions were prepared by high-pressure melt homogenization and characterized by particle size measurements, differential scanning calorimetry, X-ray diffraction and electron microscopy. To obtain fractions with very small smectic...... nanoparticles, selected dispersions were ultracentrifuged. A mixture of cholesteryl myristate and the phospholipid used for the stabilization of the dispersions was also investigated by light microscopy. The nanoparticles usually display a bimodal crystallization event which depends on the thermal treatment...

  14. Formation of isoprostane bicyclic endoperoxides from the autoxidation of cholesteryl arachidonate. (United States)

    Yin, Huiyong; Havrilla, Christine M; Morrow, Jason D; Porter, Ned A


    Autoxidation of polyunsaturated fatty acids and esters leads to a complex mixture containing hydroperoxides and cyclic peroxides. Prostaglandin bicyclic endoperoxides have been detected from the autoxidation of cholesteryl arachidonate by LC-MS and GC-MS techniques. All four possible types (I-IV) of bicyclic endoperoxides have been found starting from different regioisomeric hydroperoxides of cholesteryl arachidonate. Furthermore, the stereochemistry of Type IV bicyclic endoperoxides has been determined by conversion to pentafluorobenzyl (PFB) ester, trimethylsilyl (TMS) derivatives, and comparison with synthetic standards by the use of GC-MS. All eight possible diastereomers of the derivatized isoprostanes were observed and were separated by gas chromatography. The bicyclic endoperoxides with the two alkyl chains syn on the cyclopentane ring were formed preferentially to those with anti configuration, a result anticipated from earlier work. Substantial amounts of the anti-substituted isoprostanes, including PGF(2)(alpha), were, however, observed in the product mixture.

  15. Influence of preparation conditions and heat treatment on the properties of supercooled smectic cholesteryl myristate nanoparticles

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Bunjes, H


    is less effective even when applying the highest homogenization pressure possible but still leads to dispersions with particles in the colloidal size range. Since sterility is required for parenteral medications and is usually achieved by autoclaving for aqueous systems, the physical and chemical...... chromatography (HPTLC). The results indicate that cholesteryl myristate nanoparticles stabilized with phospholipid/sodium glycocholate, polyvinyl alcohol, poloxamer and poloxamine can be sterilized by autoclaving. Compared to cholesterol ester free dispersions of phospholipids, the phospholipid seems to be more...

  16. Evolving neural network optimization of cholesteryl ester separation by reversed-phase HPLC. (United States)

    Jansen, Michael A; Kiwata, Jacqueline; Arceo, Jennifer; Faull, Kym F; Hanrahan, Grady; Porter, Edith


    Cholesteryl esters have antimicrobial activity and likely contribute to the innate immunity system. Improved separation techniques are needed to characterize these compounds. In this study, optimization of the reversed-phase high-performance liquid chromatography separation of six analyte standards (four cholesteryl esters plus cholesterol and tri-palmitin) was accomplished by modeling with an artificial neural network-genetic algorithm (ANN-GA) approach. A fractional factorial design was employed to examine the significance of four experimental factors: organic component in the mobile phase (ethanol and methanol), column temperature, and flow rate. Three separation parameters were then merged into geometric means using Derringer's desirability function and used as input sources for model training and testing. The use of genetic operators proved valuable for the determination of an effective neural network structure. Implementation of the optimized method resulted in complete separation of all six analytes, including the resolution of two previously co-eluting peaks. Model validation was performed with experimental responses in good agreement with model-predicted responses. Improved separation was also realized in a complex biological fluid, human milk. Thus, the first known use of ANN-GA modeling for improving the chromatographic separation of cholesteryl esters in biological fluids is presented and will likely prove valuable for future investigators involved in studying complex biological samples.

  17. Calculation of the T-X phase diagrams for binary mixtures of cholestanyl myristate-cholesteryl myristate and cholestanyl myristate-cholesteryl oleate. (United States)

    Yurtseven, Hamit; Sen, Sema


    T-X phase diagrams of binary mixtures of cholestanyl myristate (CnM)-cholesteryl myristate (CrM) and cholestanyl myristate (CnM)-cholesteryl oleate (CO) are calculated using the mean field theory. We expand the free energies for the phases of cholesteric, smectic, and solid solutions in terms of the order parameters for these binary mixtures (X is the concentration of CrM for CnM-CrM and the concentration of CnM for CnM-CO). From this expansion, we obtain the phase line equations for the transitions among the isotropic liquid, cholesteric, smectic, and solid solutions for both binary mixtures. Taking into account the temperature and concentration dependences of the coefficients in the free energy expansion, we fit our phase line equations to the experimentally measured T-X phase diagrams for these two binary mixtures. Our calculated phase lines coincide with the measured T-X phase diagrams, and the critical behavior of the thermodynamic quantities, including the order parameter, the specific heat, and the susceptibility, can be predicted from the mean field expansions.

  18. Cholesteryl ester transfer-protein modulator and inhibitors and their potential for the treatment of cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Shinkai H


    Full Text Available Hisashi ShinkaiCentral Pharmaceutical Research Institute, JT Inc, Osaka, JapanAbstract: Elevated low-density lipoprotein (LDL cholesterol and lowered high-density lipoprotein (HDL cholesterol are important risk factors for cardiovascular disease. Accordingly, raising HDL cholesterol induced by cholesteryl ester transfer protein (CETP inhibition is an attractive approach for reducing the residual risk of cardiovascular events that persist in many patients receiving low-density LDL cholesterol-lowering therapy with statins. The development of torcetrapib, a CETP inhibitor, was terminated due to its adverse cardiovascular effects. These adverse effects did not influence the mechanism of CETP inhibition, but affected the molecule itself. Therefore a CETP modulator, dalcetrapib, and a CETP inhibitor, anacetrapib, are in Phase III of clinical trials to evaluate their effects on cardiovascular outcomes. In the dal-VESSEL (dalcetrapib Phase IIb endothelial function study and the dal-PLAQUE (safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging clinical studies, dalcetrapib reduced CETP activity by 50% and increased HDL cholesterol levels by 31% without changing LDL cholesterol levels. Moreover, dalcetrapib was associated with a reduction in carotid vessel-wall inflammation at 6 months, as well as a reduced vessel-wall area at 24 months compared with the placebo. In the DEFINE (determining the efficacy and tolerability of CETP inhibition with anacetrapib clinical study, anacetrapib increased HDL cholesterol levels by 138% and decreased LDL cholesterol levels by 36%. In contrast with torcetrapib, anacetrapib had no adverse cardiovascular effects. The potential of dalcetrapib and anacetrapib in the treatment of cardiovascular diseases will be revealed by two large-scale clinical trials, the dal-OUTCOMES (efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome study and the

  19. siRNA delivery into tumor cells by lipid-based nanoparticles composed of hydroxyethylated cholesteryl triamine. (United States)

    Hattori, Yoshiyuki; Nakamura, Tsukasa; Ohno, Hiroaki; Fujii, Nobutaka; Maitani, Yoshie


    Previously, we reported that cationic nanoparticles (NP) composed of cholesteryl diamine (OH-Chol, (3S)-N-(2-(2-hydroxyethylamino)ethyl)cholesteryl-3-carboxamide) and Tween 80 could deliver plasmid DNA (pDNA) and small interfering RNA (siRNA) with high transfection efficiency into various tumor cells. In this study, to facilitate the endosomal escape of siRNA transfected by lipid-based nanoparticles, we synthesized new cationic cholesteryl triamine (OH-N-Chol, (3S)-N-(2-(2-(2-hydroxyethylamino)ethylamino)ethyl)cholesteryl-3-carboxamide) with an ethylenimine extension and prepared cationic nanoparticles (NP-N) composed of cholesteryl triamine and Tween 80. Although NP-N/siRNA complex (NP-N nanoplex) after mixing NP-N with siRNA was >350 nm in size, the vortex-mixing during the nanoplex formation decreased it to about 200 nm, which was an injectable size. NP-N nanoplex was mainly internalized by macropinocytosis-mediated endocytosis, as was NP nanoplex, and showed higher gene knockdown efficiency than NP nanoplex in human cervical carcinoma SiHa cells. From these results, cationic nanoparticles composed of OH-N-Chol and Tween 80 may have potential as a gene vector for siRNA transfection to tumor cells.

  20. Plasma cholesteryl ester transfer is a determinant of intima-media thickness in type 2 diabetic and nondiabetic subjects : Role of CETP and triglycerides

    NARCIS (Netherlands)

    de Vries, R; Perton, FG; Dallinga-Thie, GM; van Roon, AM; Wolffenbuttel, BHR; van Tol, A; Dullaart, RPF


    We tested whether carotid artery intima-media thickness (IMT) is associated with plasma cholesteryl ester transfer (CET) and/or the plasma cholesteryl ester transfer protein (CETP) concentration in type 2 diabetic and control subjects. In 87 male and female subjects with type 2 diabetes (nonsmokers,

  1. The association of HDL cholesterol concentration with the-629C > A CETP promoter polymorphism is not fully explained by its relationship with plasma cholesteryl ester transfer

    NARCIS (Netherlands)

    Dullaart, R. P. F.; Borggreve, S. E.; Hillege, H. L.; Dallinga-Thie, G. M.


    Objective . HDL cholesterol is associated with the -629C>A cholesteryl ester transfer protein (CETP) promoter polymorphism. This relationship may in part be explained via effects on plasma cholesteryl ester transfer (CET), which reflects the activity of CETP in the context of endogenous lipoproteins

  2. How anacetrapib inhibits the activity of the cholesteryl ester transfer protein? Perspective through atomistic simulations.

    Directory of Open Access Journals (Sweden)

    Tarja Äijänen


    Full Text Available Cholesteryl ester transfer protein (CETP mediates the reciprocal transfer of neutral lipids (cholesteryl esters, triglycerides and phospholipids between different lipoprotein fractions in human blood plasma. A novel molecular agent known as anacetrapib has been shown to inhibit CETP activity and thereby raise high density lipoprotein (HDL-cholesterol and decrease low density lipoprotein (LDL-cholesterol, thus rendering CETP inhibition an attractive target to prevent and treat the development of various cardiovascular diseases. Our objective in this work is to use atomistic molecular dynamics simulations to shed light on the inhibitory mechanism of anacetrapib and unlock the interactions between the drug and CETP. The results show an evident affinity of anacetrapib towards the concave surface of CETP, and especially towards the region of the N-terminal tunnel opening. The primary binding site of anacetrapib turns out to reside in the tunnel inside CETP, near the residues surrounding the N-terminal opening. Free energy calculations show that when anacetrapib resides in this area, it hinders the ability of cholesteryl ester to diffuse out from CETP. The simulations further bring out the ability of anacetrapib to regulate the structure-function relationships of phospholipids and helix X, the latter representing the structural region of CETP important to the process of neutral lipid exchange with lipoproteins. Altogether, the simulations propose CETP inhibition to be realized when anacetrapib is transferred into the lipid binding pocket. The novel insight gained in this study has potential use in the development of new molecular agents capable of preventing the progression of cardiovascular diseases.

  3. Kinetics of Non-Isothermal Crystallization of Coconut-based Cholesteryl Ester: Avrami and Ozawa Approache

    Directory of Open Access Journals (Sweden)

    J. F. Joson


    Full Text Available Kinetics of non-isothermal crystallization of coconut-based cholesteryl ester was performed by differentialscanning calorimetry under various heating rates. Different analysis methods were used to describe theprocess of non-isothermal crystallization. The results showed that the Avrami equation could describe thesystem very well. However, the Ozawa analysis failed. A probable reason is the difference in the crystallizationkinetics at high and low relative crystallization. The phase transitions of the coconut-based cholesterylester were also observed through optical polarizing microscopy

  4. Interactions of egg yolk phosphatidylcholine with cholesteryl polyethoxy neoglycolipids containing N-acetyl- D-glucosamine (United States)

    Kemoun, Rachida; Gelhausen, Micaèle; Besson, Françoise; Lafont, Dominique; Buchet, René; Boullanger, Paul; Roux, Bernard


    Series of neoglycolipids containing cholesteryl and N-acetyl- D-glucosaminyl groups were synthesized with various ethoxy linkers. Their self aggregations and intermolecular interactions, without and with egg yolk phosphatidylcholine (EYPC), were characterized in dry and hydrated states, by using infrared spectroscopy. The neoglycolipids in the dry state formed intermolecular hydrogen bonds between the CO and N-H or O-H groups of N-acetyl- D-glucosamine (GlcNAc). In the presence of EYPC, these intermolecular interactions were broken and new hydrogen bonds, involving the phosphate group of EYPC and N-H or O-H groups of GlcNAc of neoglycolipid, were formed. The presence of water molecules altered these intermolecular hydrogen bonds. The CO groups of EYPC were not affected by the presence of neoglycolipids, either in hydrated or in dry states, indicating that the GlcNAc polar groups interacted mostly with EYPC phosphate residues. The phase transition-temperature of mixtures of EYPC containing either cholesterol or neoglycolipid were similar, indicating that the cholesteryl group of the neoglycolipid interacted in the same manner as cholesterol with hydrocarbon chains of EYPC. Some structural models of molecular interactions of neoglycolipids were discussed in relation with the molecular recognition of wheat germ agglutinin.

  5. Near-field infrared imaging of molecular changes in cholesteryl oleate by free electron laser infrared ablation (United States)

    Masaki, Tatsuhiro; Goto, Kazuya; Inouye, Yasushi; Kawata, Satoshi


    We have applied infrared near-field scanning optical microscopy (IR-NSOM) to enable evaluation of detailed molecular changes in cholesteryl oleate, a primary cause of arteriosclerosis. In our IR-NSOM, a wide wavelength range of 2.9-6.7 μm is achieved by use of an optical parametric amplifier and an apertured cantilever. IR irradiation from a free-electron laser (FEL) tuned to a 5.75 μm wavelength induced molecular structural changes and caused cholesteryl oleate to decompose to cholesterol and fatty acids in the FEL irradiated areas. The IR-NSOM images at two different wavelengths, 5.75 and 5.3 μm, with a 2 μm apertured cantilever probe successfully identified areas of molecular change in cholesteryl oleate beyond the diffraction limit of IR microspectroscopy. In-depth molecular structure changes were also evaluated by the IR-NSOM and we demonstrated that the FEL irradiation induced subsurface molecular structure changes throughout cholesteryl oleate in the irradiated areas.

  6. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk

    NARCIS (Netherlands)

    Thompson, Alexander; Di Angelantonio, Emanuele; Sarwar, Nadeem; Erqou, Sebhat; Saleheen, Danish; Dullaart, Robin P. F.; Keavney, Bernard; Ye, Zheng; Danesh, John


    Context The importance of the cholesteryl ester transfer protein (CETP) pathway in coronary disease is uncertain. Study of CETP genotypes can help better understand the relevance of this pathway to lipid metabolism and disease risk. Objective To assess associations of CETP genotypes with CETP phenot

  7. Patient considerations and clinical impact of cholesteryl ester transfer protein inhibitors in the management of dyslipidemia: focus on anacetrapib. (United States)

    Miyares, Marta A; Davis, Kyle


    Cardiovascular disease (CVD) is responsible for significant morbidity and mortality within the United States and worldwide. Although targeting low-density lipoprotein cholesterol (LDL-C) in the prevention of CVD has been shown to be effective, evidence exists to indicate that significant cardiovascular (CV) risk remains in patients receiving 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) - a risk that may be correlated with low levels of high-density lipoprotein cholesterol (HDL-C). Among the various tactics under investigation to increase HDL-C, inhibition of cholesteryl ester transfer protein (CETP) appears the most adept to raise these levels. Although torcetrapib, a CETP inhibitor, demonstrated significant beneficial changes in HDL-C and LDL-C after 12 months of therapy when coadministered with atorvastatin, patients in the torcetrapib arm experienced a rise in mortality, including increased risk of death from CV and non-CV causes as well as a significant rise in major CV events. Later studies established that the adverse effects of torcetrapib were produced from molecule-specific off-target effects and not to the mechanism of CETP inhibition. These untoward outcomes have not been detected with anacetrapib, the third of the CETP inhibitors to enter Phase III trials. Furthermore, treatment with anacetrapib revealed both a statistically significant decrease in LDL-C and increase in HDL-C over placebo. While the place in therapy of niacin and fibrates to reduce CV events is currently in question secondary to the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglyceride and Impact on Global Health Outcomes and the Action to Control CV Risk in Diabetes trials, the ongoing large-scale, randomized-placebo, controlled-outcomes study with anacetrapib coadministered with statin treatment will not only test the hypothesis if CETP inhibition lowers residual CV risk but will also provide insight as to which patient

  8. Triphenylethanamine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors: Discovery of N-[(1R)-1-(3-Cyclopropoxy-4-fluorophenyl)-1-[3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-phenylethyl]-4-fluoro-3-(trifluoromethyl)benzamide (BMS-795311). (United States)

    Qiao, Jennifer X; Wang, Tammy C; Adam, Leonard P; Chen, Alice Ye A; Taylor, David S; Yang, Richard Z; Zhuang, Shaobin; Sleph, Paul G; Li, Julia P; Li, Danshi; Yin, Xiaohong; Chang, Ming; Chen, Xue-Qing; Shen, Hong; Li, Jianqing; Smith, Daniel; Wu, Dauh-Rurng; Leith, Leslie; Harikrishnan, Lalgudi S; Kamau, Muthoni G; Miller, Michael M; Bilder, Donna; Rampulla, Richard; Li, Yi-Xin; Xu, Carrie; Lawrence, R Michael; Poss, Michael A; Levesque, Paul; Gordon, David A; Huang, Christine S; Finlay, Heather J; Wexler, Ruth R; Salvati, Mark E


    Cholesteryl ester transfer protein (CETP) inhibitors raise HDL-C in animals and humans and may be antiatherosclerotic by enhancing reverse cholesterol transport (RCT). In this article, we describe the lead optimization efforts resulting in the discovery of a series of triphenylethanamine (TPE) ureas and amides as potent and orally available CETP inhibitors. Compound 10g is a potent CETP inhibitor that maximally inhibited cholesteryl ester (CE) transfer activity at an oral dose of 1 mg/kg in human CETP/apoB-100 dual transgenic mice and increased HDL cholesterol content and size comparable to torcetrapib (1) in moderately-fat fed hamsters. In contrast to the off-target liabilities with 1, no blood pressure increase was observed with 10g in rat telemetry studies and no increase of aldosterone synthase (CYP11B2) was detected in H295R cells. On the basis of its preclinical profile, compound 10g was advanced into preclinical safety studies.

  9. Cholesteryl oligoethyleneglycol glycosides: fluidizing effect of their embedment into phospholipid bilayers. (United States)

    Bardonnet, Pierre-Louis; Faivre, Vincent; Pirot, Fabrice; Boullanger, Paul; Falson, Françoise


    Glycosides of cholesteryl oligoethyleneglycols have been synthesized and embedded in liposome bilayers. Several methods as steady-state fluorescence polarization, differential scanning calorimetry, zeta potential, and agglutination have been used to describe the physicochemical outcome of the incorporation of these synthetic glycolipids within phospholipid layers. From calorimetry and fluorescence experiments, it is apparent that the glycolipids decrease the transition temperature of the bilayers in a more important extent than cholesterol. Furthermore, the thickness of the aqueous layer fixed around the liposome is independent of the presence of glycolipids, suggesting that their hydrophilic parts (tetraethyleneglycol spacer and sugar moiety) are not completely extended towards the aqueous phase. Nevertheless, an important and specific interaction has been observed between such glycosylated liposomes and vegetal lectins.

  10. Severe chronic diarrhea and weight loss in cholesteryl ester storage disease: A case report

    Institute of Scientific and Technical Information of China (English)

    Uta Drebber; Matthias Andersen; Hans U Kasper; Peter Lohse; Manfred Stolte; Hans P Dienes


    AIM: An inherited deficiency of human lysosomal acid lipase (LAL)results in the rare conditions of Wolman disease and cholesteryl ester storage disease (CESD). We want to present the rare case of CESD in an adult.METHODS: We report about an adult female patient with severe chronic diarrhea and weight loss as a consequence of CESD. Clinical examination revealed signs of malabsorption and slightly elevated liver enzymes.RESULTS: Histopathologic changes in the liver tissue and DNA sequence analysis confirmed the diagnosis of CESD due to homozygosity for the most common CESD mutation,a G934A splice site defect encoded by exon 8 of the lysosomal acid lipase (LIPA) gene.CONCLUSION: It is the first case in the literature with diarrhea as a putative symptom of CESD in adult patients.

  11. Macrophage cholesterol homeostasis and metabolic diseases: critical role of cholesteryl ester mobilization. (United States)

    Ghosh, Shobha


    Atherogenic dyslipidemia, including low HDL levels, is the major contributor of residual risk of cardiovascular disease that remains even after aggressive statin therapy to reduce LDL-cholesterol. Currently, distinction is not made between HDL-cholesterol and HDL, which is a lipoprotein consisting of several proteins and a core containing cholesteryl esters (CEs). The importance of assessing HDL functionality, specifically its role in facilitating cholesterol efflux from foam cells, is relevant to atherogenesis. Since HDLs can only remove unesterified cholesterol from macrophages while cholesterol is stored as CEs within foam cells, intracellular CE hydrolysis by CE hydrolase is vital. Reduction in macrophage lipid burden not only attenuates atherosclerosis but also reduces inflammation and linked pathologies such as Type 2 diabetes and chronic kidney disease. Targeting reduction in macrophage CE levels and focusing on enhancing cholesterol flux from peripheral tissues to liver for final elimination is proposed.

  12. A New Initiator Cholesteryl Chloroformate for Cupper-Based Atom Transfer Radical Polymerization of Methyl Methacrylate

    Institute of Scientific and Technical Information of China (English)

    曹健; 楚娟; 张可达


    The polymerization of metyl methacrylate (MMA) was studied in detail by use of CuCl/L as a catalyst and cholesteryl chloroformate (CC) as an initiator. It was found that the atom transfer radical polymerization of MMA could proceed when L equals to a multidentate aliphatic amine ligand, N,N,N',N",N"-penta(methyl acrylate)diethylenetriamine (MA5-DETA), and no polymerization was occurred while L=2,2'-bipyridine and 1,10-phenanthroline. The linear proportionality of the molecular weights to the conversions and straight lines observed in ln[M]0/[M] versus time plots indicated that the present polymerization system had the typical controlled polymerization characteristics.

  13. Cholesteryl ester transfer protein, low density lipoprotein particle size and intima media thickness in patients with coronary heart disease. (United States)

    Tosheska, Katerina; Labudovic, Danica; Jovanova, Silvana; Jaglikovski, Branko; Alabakovska, Sonja


    Cholesteryl ester transfer protein (CETP) plays a key role in reverse cholesterol transport and high density lipoprotein (HDL) metabolism. Predominance of small, dense LDL particles is associated with an increased risk of atherosclerosis and coronary heart disease (CHD).The aim of the study was to determine the potential relationship between the CETP concentration and low density lipoprotein (LDL) particle size and their association with intima media thickness (IMT) in patients with CHD. Lipid parameters, CETP concentration and LDL particle size were determined in 100 healthy subjects (control group) and in 100 patients with CHD, aged 43 to 77 years. Plasma CETP concentrations were measured by an enzyme-linked immuno-sorbent assay with two different monoclonal antibodies. LDL subclasses were separated by nondenaturing polyacrilamide 3-31% gradient gel electrophoresis. CETP concentration was higher in patients compared to controls (2.02 ± 0.75 mg/ml vs. 1.74 ± 0.63 mg/ml, p<0.01). Mean LDL particle size (nm) was significantly smaller in patients than in controls (24.5 ± 1.1 vs. 26.1 ± 0.9; p<0.001). There was no relation between LDL particle size and CETP concentration (r=-0.1807, p=0.072). Age, diastolic blood pressure, CETP concentration and LDL particle size were independent factors for determing IMT by multiple linear regression analysis. They accounted for 35.2 % of the observed variability in IMT. CETP is not an independent contributor of LDL particle size. CETP might play a role in determining lipoprotein distributions, but did not seem to be the sole factor in the formation of small LDL particles.

  14. Cholesteryl Ester Hydroperoxides Are Biologically Active Components of Minimally Oxidized Low Density Lipoprotein*S⃞ (United States)

    Harkewicz, Richard; Hartvigsen, Karsten; Almazan, Felicidad; Dennis, Edward A.; Witztum, Joseph L.; Miller, Yury I.


    Oxidation of low density lipoprotein (LDL) occurs in vivo and significantly contributes to the development of atherosclerosis. An important mechanism of LDL oxidation in vivo is its modification with 12/15-lipoxygenase (LO). We have developed a model of minimally oxidized LDL (mmLDL) in which native LDL is modified by cells expressing 12/15LO. This mmLDL activates macrophages inducing membrane ruffling and cell spreading, activation of ERK1/2 and Akt signaling, and secretion of proinflammatory cytokines. In this study, we found that many of the biological activities of mmLDL were associated with cholesteryl ester (CE) hydroperoxides and were diminished by ebselen, a reducing agent. Liquid chromatography coupled with mass spectroscopy demonstrated the presence of many mono- and polyoxygenated CE species in mmLDL but not in native LDL. Nonpolar lipid extracts of mmLDL activated macrophages, although to a lesser degree than intact mmLDL. The macrophage responses were also induced by LDL directly modified with immobilized 12/15LO, and the nonpolar lipids extracted from 12/15LO-modified LDL contained a similar set of oxidized CE. Cholesteryl arachidonate modified with 12/15LO also activated macrophages and contained a similar collection of oxidized CE molecules. Remarkably, many of these oxidized CE were found in the extracts of atherosclerotic lesions isolated from hyperlipidemic apoE–/– mice. These results suggest that CE hydroperoxides constitute a class of biologically active components of mmLDL that may be relevant to proinflammatory activation of macrophages in atherosclerotic lesions. PMID:18263582

  15. Lysosomal lipase deficiency: molecular characterization of eleven patients with Wolman or cholesteryl ester storage disease. (United States)

    Fasano, Tommaso; Pisciotta, Livia; Bocchi, Letizia; Guardamagna, Ornella; Assandro, Paola; Rabacchi, Claudio; Zanoni, Paolo; Filocamo, Mirella; Bertolini, Stefano; Calandra, Sebastiano


    Wolman Disease (WD) and cholesteryl ester storage disease (CESD) represent two distinct phenotypes of the same recessive disorder caused by the complete or partial deficiency of lysosomal acidic lipase (LAL), respectively. LAL, encoded by the LIPA gene, hydrolyzes cholesteryl esters derived from cell internalization of plasma lipoproteins. WD is a rapidly progressive and lethal disease characterized by intestinal malabsorption, hepatic and adrenal failure. CESD is characterized by hepatic fibrosis, hyperlipidemia and accelerated atherosclerosis. Aim of the study was the identification of LIPA mutations in three WD and eight CESD patients. The WD patients, all deceased before the first year of age, were homozygous for two novel mutations (c.299+1G>A and c.419G>A) or a mutation (c.796G>T) previously reported as compound heterozygosity in a CESD patient. The two mutations (c.419G>A and c.796G>T) resulting in truncated proteins (p.W140* and p.G266*) and the splicing mutation (c.229+1G>A) were associated with undetectable levels of LIPA mRNA in fibroblasts. All eight CESD patients carried the common mutation c.894G>A known to result not only in a major non-functional transcript with the skipping of exon 8 (p.S275_Q298del), but also in a minor normally spliced transcript producing 5-10% residual LAL activity. The c.894G>A mutation was found in homozygosity in four patients and, as compound heterozygosity, in association with a known (p.H295Y and p.G342R) or a novel (p.W140*) mutation in four other CESD patients. Segregation analysis performed in all patients harboring c.895G>A showed its occurrence on the same haplotype suggesting a common founder ancestor. The other WD and CESD mutations were associated with different haplotypes.

  16. Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes

    NARCIS (Netherlands)

    Dullaart, RPF; Riemens, SC; Scheek, LM; van Tol, A


    Background Plasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high-density lipoproteins (HDLs) towards apolipoprotein (apo) B-containing lipoproteins are key steps in HDL metabolism. Materials and methods The effects of exogenous hyperinsulinaemia on plasma

  17. Genetic variants in CETP increase risk of intracerebral hemorrhage

    NARCIS (Netherlands)

    Anderson, Christopher D.; Falcone, Guido J.; Phuah, Chia Ling; Radmanesh, Farid; Brouwers, H. Bart; Battey, Thomas W K; Biffi, Alessandro; Peloso, Gina M.; Liu, Dajiang J.; Ayres, Alison M.; Goldstein, Joshua N.; Viswanathan, Anand; Greenberg, Steven M.; Selim, Magdy; Meschia, James F.; Brown, Devin L.; Worrall, Bradford B.; Silliman, Scott L.; Tirschwell, David L.; Flaherty, Matthew L.; Kraft, Peter; Jagiella, Jeremiasz M.; Schmidt, Helena; Hansen, Björn M.; Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Elosua, Roberto; Cuadrado-Godia, Elisa; Soriano, Carolina; van Nieuwenhuizen, Koen M.; Klijn, Catharina J M; Rannikmae, Kristiina; Samarasekera, Neshika; Salman, Rustam Al Shahi; Sudlow, Catherine L.; Deary, Ian J.; Morotti, Andrea; Pezzini, Alessandro; Pera, Joanna; Urbanik, Andrzej; Pichler, Alexander; Enzinger, Christian; Norrving, Bo; Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar; Roquer, Jaume; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Kidwell, Chelsea S.; Kittner, Steven J.; Waddy, Salina P.; Langefeld, Carl D.; Abecasis, Goncalo; Willer, Cristen J.; Kathiresan, Sekar; Woo, Daniel; Rosand, Jonathan


    Objective: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C;

  18. Spacer effect on nanostructures and self-assembly in organogels via some bolaform cholesteryl imide derivatives with different spacers (United States)

    Jiao, Tifeng; Gao, Fengqing; Zhang, Qingrui; Zhou, Jingxin; Gao, Faming


    In this paper, new bolaform cholesteryl imide derivatives with different spacers were designed and synthesized. Their gelation behaviors in 23 solvents were investigated, and some of them were found to be low molecular mass organic gelators. The experimental results indicated that these as-formed organogels can be regulated by changing the flexible/rigid segments in spacers and organic solvents. Suitable combination of flexible/rigid segments in molecular spacers in the present cholesteryl gelators is favorable for the gelation of organic solvents. Scanning electron microscopy and atomic force microscopy observations revealed that the gelator molecules self-assemble into different aggregates, from wrinkle and belt to fiber with the change of spacers and solvents. Spectral studies indicated that there existed different H-bond formations between imide groups and assembly modes, depending on the substituent spacers in molecular skeletons. The present work may give some insight into the design and character of new organogelators and soft materials with special molecular structures.

  19. Self-Assembly and Nanostructures in Organogels Based on a Bolaform Cholesteryl Imide Compound with Conjugated Aromatic Spacer



    The self-assembly of small functional molecules into supramolecular structures is a powerful approach toward the development of new nanoscale materials and devices. As a class of self-assembled materials, low weight molecular organic gelators, organized in special nanoarchitectures through specific non-covalent interactions, has become one of the hot topics in soft matter research due to their scientific values and many potential applications. Here, a bolaform cholesteryl imide compound with ...

  20. Aspartame-fed zebrafish exhibit acute deaths with swimming defects and saccharin-fed zebrafish have elevation of cholesteryl ester transfer protein activity in hypercholesterolemia. (United States)

    Kim, Jae-Yong; Seo, Juyi; Cho, Kyung-Hyun


    Although many artificial sweeteners (AS) have safety issues, the AS have been widely used in industry. To determine the physiologic effect of AS in the presence of hyperlipidemia, zebrafish were fed aspartame or saccharin with a high-cholesterol diet (HCD). After 12 days, 30% of zebrafish, which consumed aspartame and HCD, died with exhibiting swimming defects. The aspartame group had 65% survivability, while the control and saccharin groups had 100% survivability. Under HCD, the saccharin-fed groups had the highest increase in the serum cholesterol level (599 mg/dL). Aspartame-fed group showed a remarkable increase in serum glucose (up to 125 mg/dL), which was 58% greater than the increase in the HCD alone group. The saccharin and HCD groups had the highest cholesteryl ester transfer protein (CETP) activity (52% CE-transfer), while the HCD alone group had 42% CE-transfer. Histologic analysis revealed that the aspartame and HCD groups showed more infiltration of inflammatory cells in the brain and liver sections. Conclusively, under presence of hyperlipidemia, aspartame-fed zebrafish exhibited acute swimming defects with an increase in brain inflammation. Saccharin-fed zebrafish had an increased atherogenic serum lipid profile with elevation of CETP activity.

  1. Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages but unchanged in macrophages lacking KIAA1363. (United States)

    Buchebner, Marlene; Pfeifer, Thomas; Rathke, Nora; Chandak, Prakash G; Lass, Achim; Schreiber, Renate; Kratzer, Adelheid; Zimmermann, Robert; Sattler, Wolfgang; Koefeler, Harald; Fröhlich, Eleonore; Kostner, Gerhard M; Birner-Gruenberger, Ruth; Chiang, Kyle P; Haemmerle, Guenter; Zechner, Rudolf; Levak-Frank, Sanja; Cravatt, Benjamin; Kratky, Dagmar


    Cholesteryl ester (CE) accumulation in macrophages represents a crucial event during foam cell formation, a hallmark of atherogenesis. Here we investigated the role of two previously described CE hydrolases, hormone-sensitive lipase (HSL) and KIAA1363, in macrophage CE hydrolysis. HSL and KIAA1363 exhibited marked differences in their abilities to hydrolyze CE, triacylglycerol (TG), diacylglycerol (DG), and 2-acetyl monoalkylglycerol ether (AcMAGE), a precursor for biosynthesis of platelet-activating factor (PAF). HSL efficiently cleaved all four substrates, whereas KIAA1363 hydrolyzed only AcMAGE. This contradicts previous studies suggesting that KIAA1363 is a neutral CE hydrolase. Macrophages of KIAA1363(-/-) and wild-type mice exhibited identical neutral CE hydrolase activity, which was almost abolished in tissues and macrophages of HSL(-/-) mice. Conversely, AcMAGE hydrolase activity was diminished in macrophages and some tissues of KIAA1363(-/-) but unchanged in HSL(-/-) mice. CE turnover was unaffected in macrophages lacking KIAA1363 and HSL, whereas cAMP-dependent cholesterol efflux was influenced by HSL but not by KIAA1363. Despite decreased CE hydrolase activities, HSL(-/-) macrophages exhibited CE accumulation similar to wild-type (WT) macrophages. We conclude that additional enzymes must exist that cooperate with HSL to regulate CE levels in macrophages. KIAA1363 affects AcMAGE hydrolase activity but is of minor importance as a direct CE hydrolase in macrophages.

  2. Neutron Scattering Studies of the Effects of Formulating Amphotericin B with Cholesteryl Sulfate on the Drug's Interactions with Phospholipid and Phospholipid-Sterol Membranes. (United States)

    Foglia, F; Rogers, S E; Webster, J R P; Akeroyd, F A; Gascoyne, K F; Lawrence, M J; Barlow, D J


    Langmuir surface pressure, small-angle neutron scattering (SANS), and neutron reflectivity (NR) studies have been performed to determine how formulation of the antifungal drug amphotericin B (AmB), with sodium cholesteryl sulfate (SCS)-as in Amphotec-affects its interactions with ergosterol-containing (model fungal cell) and cholesterol-containing (model mammalian cell) membranes. The effects of mixing AmB in 1:1 molar ratio with cholesteryl sulfate (yielding AmB-SCS micelles) are compared against those of free AmB, using monolayers and bilayers formed from palmitoyloleoylphosphatidylcholine (POPC) in the absence and presence of 30 mol % ergosterol or cholesterol, in all cases employing a 1:0.05 molar ratio of lipid:AmB. Analyses of the (bilayer) SANS and (monolayer) NR data indicate that the equilibrium changes in membrane structure induced in sterol-free and sterol-containing membranes are the same for free AmB and AmB-SCS. Stopped-flow SANS experiments, however, reveal that the structural changes to vesicle membranes occur far more rapidly following exposure to AmB-SCS vs free drug, with the kinetics of these changes varying with membrane composition. With POPC vesicles, the structural changes induced by AmB-SCS become apparent only after several minutes, and equilibrium is reached after ∼30 min. The corresponding onset of changes in POPC-ergosterol and POPC-cholesterol vesicles, however, occurs within ∼5 s, with equilibrium reached after 10 and 120 s, respectively. The rate of insertion of AmB into POPC-sterol membranes is thus increased through formulation as AmB-SCS. Moreover, the differences in monolayer surface pressure and SANS structure-change equilibration times suggest significant rearrangement of AmB within these membranes following insertion. The reduced times to equilibrium for the POPC-ergosterol vs POPC-cholesterol systems are consistent with the known differences in affinity of AmB for these two sterols, and the reduced time to equilibrium for

  3. Hepatic expression of inflammatory genes and microRNAs in pigs with high “cholesteryl ester transfer protein” (CETP) activity

    DEFF Research Database (Denmark)

    Cirera, Susanna; Tørsleff, Benedicte C Juul; Ritz, Christian


    with obesity; e.g., low levels of high-density lipoproteins (HDL) are high risk factors of cardiovascular events. A number of genetic, lifestyle, and environmental factors have been shown to contribute to the lowering of HDL-cholesterol. One of these factors is cholesteryl ester transfer protein (CETP......) promoting the redistribution of cholesteryl esters, triglycerides, and phospholipids between plasma proteins. Moreover, obesity and ORD are often linked with chronic low-grade inflammation leading to insulin resistance and endothelial and microvascular dysfunctions. The aim of this study was to detect...

  4. Insights into the Tunnel Mechanism of Cholesteryl Ester Transfer Protein through All-atom Molecular Dynamics Simulations. (United States)

    Lei, Dongsheng; Rames, Matthew; Zhang, Xing; Zhang, Lei; Zhang, Shengli; Ren, Gang


    Cholesteryl ester transfer protein (CETP) mediates cholesteryl ester (CE) transfer from the atheroprotective high density lipoprotein (HDL) cholesterol to the atherogenic low density lipoprotein cholesterol. In the past decade, this property has driven the development of CETP inhibitors, which have been evaluated in large scale clinical trials for treating cardiovascular diseases. Despite the pharmacological interest, little is known about the fundamental mechanism of CETP in CE transfer. Recent electron microscopy (EM) experiments have suggested a tunnel mechanism, and molecular dynamics simulations have shown that the flexible N-terminal distal end of CETP penetrates into the HDL surface and takes up a CE molecule through an open pore. However, it is not known whether a CE molecule can completely transfer through an entire CETP molecule. Here, we used all-atom molecular dynamics simulations to evaluate this possibility. The results showed that a hydrophobic tunnel inside CETP is sufficient to allow a CE molecule to completely transfer through the entire CETP within a predicted transfer time and at a rate comparable with those obtained through physiological measurements. Analyses of the detailed interactions revealed several residues that might be critical for CETP function, which may provide important clues for the effective development of CETP inhibitors and treatment of cardiovascular diseases.

  5. Detection and characterization of cholesteryl ester hydroperoxides in oxidized LDL and oxidized HDL by use of an Orbitrap mass spectrometer. (United States)

    Hui, Shu-Ping; Sakurai, Toshihiro; Ohkawa, Futaba; Furumaki, Hiroaki; Jin, Shigeki; Fuda, Hirotoshi; Takeda, Seiji; Kurosawa, Takao; Chiba, Hitoshi


    Oxidation of cholesteryl esters in lipoproteins by reactive oxygen species yields cholesteryl ester hydroperoxides (CEOOH). In this study, we developed a novel method for identification and characterization of CEOOH molecules in human lipoproteins by use of reversed-phase liquid chromatography with an hybrid linear ion trap-Orbitrap mass spectrometer (LC-LTQ Orbitrap). Electrospray ionization tandem mass spectrometric analysis was performed in both positive-ion and negative-ion modes. Identification of CEOOH molecules was completed by use of high-mass-accuracy (MA) mass spectrometric data obtained by using the spectrometer in Fourier-transform (FT) mode. Native low-density lipoproteins (nLDL) and native high-density lipoproteins (nHDL) from a healthy donor were oxidized by CuSO(4), furnishing oxidized LDL (oxLDL) and oxidized HDL (oxHDL). No CEOOH molecules were detected in the nLDL and the nHDL, whereas six CEOOH molecules were detected in the oxLDL and the oxHDL. In positive-ion mode, CEOOH was detected as [M + NH(4)](+) and [M + Na](+) ions. In negative-ion mode, CEOOH was detected as [M + CH(3)COO](-) ions. CEOOH were more easily ionized in positive-ion mode than in negative-ion mode. The LC-LTQ Orbitrap method was applied to human plasma and six species of CEOOH were detected. The limit of detection was 0.1 pmol (S/N = 5:1) for synthesized CEOOH.

  6. High level of serum cholesteryl ester transfer protein inactive hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)


    AIM To determine the significance of cholesteryl estertransfer protein (CETP) in lipoprotein abnormalities inchronic hepatitis C virus (HCV) infection.METHODS: We evaluated the significance of the serumconcentration of CETP in 110 Japanese patients withchronic HCV infection. Fifty-five patients had active HCVinfection, and HCV eradication had been achieved in55. The role of CETP in serum lipoprotein abnormalities,specifically, in triglyceride (TG) concentrations in thefour major classes of lipoproteins, was investigatedusing Pearson correlations in conjunction with multipleregression analysis and compared them between thosewith active HCV infection and those in whom eradicationhad been achieved.RESULTS: The serum CETP levels of patients withactive HCV infection were significantly higher than thoseof patients in whom HCV eradication was achieved(mean ± SD, 2.84 ± 0.69 μg/mL vs 2.40 ± 1.00 μg/mL, P = 0.008). In multiple regression analysis, HCVinfection status (active or eradicated) was an independentfactor significantly associated with the serumCETP level. TG concentrations in low-density lipoprotein(mean ± SD, 36.25 ± 15.28 μg/mL vs 28.14 ± 9.94μg/mL, P = 0.001) and high-density lipoprotein (HDL)(mean ± SD, 25.9 ± 7.34 μg/mL vs 17.17 ± 4.82μg/mL, P 〈 0.001) were significantly higher in patients with active HCV infection than in those in whom HCVeradication was achieved. The CETP level was stronglycorrelated with HDL-TG in patients with active HCVinfection (R = 0.557, P 〈 0.001), whereas CETP wasnot correlated with HDL-TG in patients in whom HCVeradication was achieved (R = -0.079, P = 0.56).CONCLUSION: Our results indicate that CETP playsa role in abnormalities of lipoprotein metabolism inpatients with chronic HCV infection.

  7. Type 2 diabetes mellitus is associated with differential effects on plasma cholesteryl ester transfer protein and phospholipid transfer protein activities and concentrations

    NARCIS (Netherlands)

    Dullaart, RPF; De Vries, R; Scheek, L; Borggreve, SE; Van Gent, T; Dallinga-Thie, GM; Ito, M; Nagano, M; Sluiter, WJ; Hattori, H; Van Tol, A


    Background: Human plasma contains two lipid transfer proteins, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), which are crucial in reverse cholesterol transport. Methods: Plasma CETP and PLTP activity levels and concentrations in 16 type 2 diabetic patients and 1

  8. The effect of cholesteryl ester transfer protein-629C -> A promoter polymorphism on high-density lipoprotein cholesterol is dependent on serum triglycerides

    NARCIS (Netherlands)

    Borggreve, SE; Hillege, HL; Wolffenbuttel, BHR; de Jong, PE; Bakker, SJL; van der Steege, G; van Tol, A; Dullaart, RPF


    Context: The -629C -> A cholesteryl ester transfer protein (CETP) promoter polymorphism is a determinant of HDL cholesterol (HDL-C). The effect of the closely linked CETP TaqIB polymorphism on HDL-C has been suggested to be modified by obesity and hyperinsulinemia. Objective: Because the CETP-mediat

  9. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans : a randomized phase II dose-response study

    NARCIS (Netherlands)

    de Grooth, Greetje J.; Kuivenhoven, Jan Albert; Stalenhoef, Anton F.H.; de Graaf, Jacqueline; Zwinderman, Aeilko H.; Posma, Jan L.; van Tol, Arie; Kastelein, John J.P.


    BACKGROUND: Cholesteryl ester transfer protein (CETP) mediates the transfer of neutral lipids between lipoproteins. High plasma levels of CETP are correlated with low HDL cholesterol levels, a strong risk factor for coronary artery disease. In earlier studies, JTT-705, a novel CETP inhibitor, was sh

  10. Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study.

    NARCIS (Netherlands)

    Katan, M.B.; Deslypere, J.P.; Birgelen, van A.P.J.M.; Wennekes-Penders, M.M.H.; Zegwaard, M.J.


    Tissue levels of n-3 fatty acids reflect dietary intake, but quantitative data about rate of incorporation and levels as a function of intake are scarce. We fed 58 men 0, 3, 6, or 9 g/d of fish oil for 12 months and monitored fatty acids in serum cholesteryl esters, erythrocytes, and subcutaneous fa

  11. Comparison of fatty acid proportions in serum cholesteryl esters among people with different glucose tolerance status: The CoDAM study

    NARCIS (Netherlands)

    Woudenbergh, van G.J.; Kuijsten, A.; Kallen, C.J.; Greevenbroek, M.M.; Stehouwer, C.D.; Blaak, E.E.; Feskens, E.J.M.


    Background and aim - Altered fatty acid patterns in blood may be associated with insulin resistance and related disorders. We investigated whether serum proportions of cholesteryl fatty acids and desaturase activity are associated with glucose tolerance status and insulin resistance. Methods and res

  12. The effect of cholesteryl ester transfer protein -629C→A promoter polymorphism on high-density lipoprotein cholesterol is dependent on serum triglycerides

    NARCIS (Netherlands)

    S.E. Borggreve (Susanna); H.L. Hillege (Hans); B.H.R. Wolffenbuttel (Bruce); P. de Jong (Paul); S.J.L. Bakker (Stephan); G. van der Steege (Gerrit); A. van Tol (Arie); R.P.F. Dullaart (Robin)


    textabstractContext: The -629C→A cholesteryl ester transfer protein (CETP) promoter polymorphism is a determinant of HDL cholesterol (HDL-C). The effect of the closely linked CETP TaqIB polymorphism on HDL-C has been suggested to be modified by obesity and hyperinsulinemia. Objective: Because the CE

  13. HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (-629C > A) and modified by glucocorticoid treatment

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; van den Berg, Gerrit; van der Knaap, Aafke M.; Dijck-Brouwer, Janneke; Dallinga-Thie, Geesje M.; Zelissen, Peter M. J.; Sluiter, Wim J.; van Beek, Andre P.


    Objective: GH replacement lowers total cholesterol and low-density lipoprotein cholesterol (LDL-C) in GH-deficient adults, but effects on high-density lipoprotein (HDL) cholesterol (HDL-C) are variable. Both GH and glucocorticoids decrease cholesteryl ester transfer protein (CETP) activity, which is

  14. Single nucleotide polymorphisms in cholesteryl ester transfer protein gene and recurrent coronary heart disease or mortality in patients with established atherosclerosis. (United States)

    Virani, Salim S; Lee, Vei-Vei; Brautbar, Ariel; Grove, Megan L; Nambi, Vijay; Alam, Mahboob; Elayda, MacArthur; Wilson, James M; Willerson, James T; Boerwinkle, Eric; Ballantyne, Christie M


    It is not known whether genetic variants in the cholesteryl ester transfer protein (CETP) gene are associated with recurrent coronary heart disease events or mortality in secondary prevention patients. Among 3,717 patients with acute coronary syndrome or coronary artery bypass grafting (CABG) enrolled in a prospective genetic registry, we evaluated whether CETP gene variants previously shown to be associated with reduced CETP activity and high-density lipoprotein cholesterol increase ("A" allele for both TaqIB [rs708272] and rs12149545) are associated with a reduction in recurrent myocardial infarction (MI), recurrent revascularization, or death. At 4.5 years of follow-up, 439 recurrent MI, 698 recurrent revascularizations, and 756 deaths occurred. Using an additive model of inheritance, the "A" allele for rs708272 was not associated with recurrent MI (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.78 to 1.17 for AG; HR 0.89, 95% CI 0.67 to 1.19 for AA; compared with GG genotype), recurrent revascularization (HR 1.13, 95% CI 0.95 to 1.33 for AG; HR 1.05, 95% CI 0.84 to 1.32 for AA), or mortality (HR 1.02, 95% CI 0.86 to 1.19 for AG; HR 1.11, 95% CI 0.91 to 1.37 for AA) in the overall cohort. Similar results were seen for the "A" allele for rs12149545. In the CABG subgroup, AG genotype for rs708272 was associated with an increased mortality (HR 1.38, 95% CI 1.06 to 1.79) compared with GG genotype. Results remained consistent using dominant model of inheritance. In conclusion, genetic CETP variants were not associated with recurrent MI or recurrent revascularization in overall cohort with a possible mortality increase in patients who underwent CABG.

  15. CoMFA, CoMSIA and Eigenvalue Analysis on Dibenzodioxepinone and Dibenzodioxocinone Derivatives as Cholesteryl Ester Transfer Protein Inhibitors

    Directory of Open Access Journals (Sweden)

    Mao-sheng Cheng


    Full Text Available Abstract: CoMFA, CoMSIA and eigenvalue analysis (EVA were performed to study the structural features of 61 diverse dibenzodioxepinone and dibenzodioxocinone analogues to probe cholesteryl ester transfer protein (CETP inhibitory activity. Three methods yielded statistically significant models upon assessment of cross-validation, bootstrapping, and progressive scrambling. This was further validated by an external set of 13 derivatives. Our results demonstrate that three models have a good interpolation as well as extrapolation. The hydrophobic features were confirmed to contribute significantly to inhibitor potencies, while a pre-oriented hydrogen bond provided by the hydroxyl group at the 3-position indicated a good correlation with previous SAR, and a hydrogen bond acceptor may play a crucial role in CETP inhibition. These derived models may help us to gain a deeper understanding of the binding interaction of these lactone-based compounds and aid in the design of new potent compounds against CETP.

  16. The role of cholesteryl ester transfer protein and phospholipid transfer protein in the remodeling of plasma high-density lipoproteins. (United States)

    Lagrost, L


    Recent studies demonstrated that alterations in the size distribution of high-density lipoproteins (HDLs) constitute reliable markers for the risk of coronary artery disease. These observations suggested that the determination of the size distribution of HDL subpopulations by using polyacrylamide gradient gel electrophoresis might constitute an effective tool in clinical practice for the detection of patients with elevated risk. During the last decade, concordant observations revealed that all the HDL subpopulations are metabolically interrelated, and their relative abundances are dependent on the activity of several plasma factors, among them the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP). As reviewed in the present article, although both CETP and PLTP can promote the size redistribution or conversion of HDL, the two plasma lipid transfer proteins can alter differently the plasma HDL distribution profile through distinct mechanisms. (Trends Cardiovasc Med 1997;7:218-224). © 1997, Elsevier Science Inc.

  17. Fabrication and humidity sensing performance studies of a fluorescent film based on a cholesteryl derivative of perylene bisimide. (United States)

    Zhang, Shujuan; Zhou, Feng; Peng, Haonan; Liu, Taihong; Ding, Liping; Fang, Yu


    A fluorescent film based on a cholesteryl derivative of perylene bisimide (PTCDI-co-CholDEA) was fabricated via utilization of an electrostatic spinning technique on a glass plate surface. SEM studies revealed that the film was characterized by fibrous network structure. It is the structure and the chemical composition that make the fluorescence emission of the film sensitive to the variation of local environmental humidity. The sensitivity of the sensing is 0.1497 (×10(4)a.u. of the intensity)/1% RH, of which RH is the abbreviation of relative humidity. The maximum quenching efficiency of the film is 55.4% when humidity reaches 97% RH. Furthermore, the sensing process is fully reversible, and presence of other commonly found liquids shows little effect to the monitoring process.

  18. Effects of oxidation on the hydrolysis by cholesterol esterase of sitosteryl esters as compared to a cholesteryl ester. (United States)

    Julien-David, Diane; Ennahar, Saïd; Miesch, Michel; Geoffroy, Philippe; Raul, Francis; Aoude-Werner, Dalal; Lessinger, Jean-Marc; Marchioni, Eric


    Phytosteryl esters (PE) are used as ingredients in functional food to decrease plasma concentration of low density lipoprotein-cholesterol (LDL-C). Effective impairment of cholesterol absorption by PE suggests that these esters are hydrolyzed by the pancreatic cholesterol esterase (CEase, EC and the liberated sterol may interfere with cholesterol reducing its intestinal absorption. PE-enriched foods are marketed for cooking purposes, and temperature is one of the most important factors leading to the formation of oxidation products. Very little is known about the outcome of PE oxides during the digestive process. A new analytical method based on mass spectrometric detection directly after enzymatic reaction was developed to determine in vitro the activity of CEase on PE and their oxides present in functional food. Using this method, we identified a new inhibitor of CEase: sitosteryl 9,10-dihydroxystearate, which behaves as a non-competitive inhibitor of the hydrolysis of cholesteryl oleate and sitosteryl oleate.

  19. Expression of the human apolipoprotein A-I gene in transgenic mice alters high density lipoprotein (HDL) particle size distribution and diminishes selective uptake of HDL cholesteryl esters

    Energy Technology Data Exchange (ETDEWEB)

    Chajekshaul, T.; Hayek, T.; Walsh, A.; Breslow, J.L. (Rockefeller University, New York, NY (USA))


    Transgenic mice carrying the human apolipoprotein (apo) A-I gene (HuAITg mice) were used to examine the effects of overexpression of the human gene on high density lipoprotein (HDL) particle size distribution and metabolism. On a chow diet, control mice had HDL cholesterol and apo A-I levels of 49 {plus minus} 2 and 137 {plus minus} 12 mg/dl of plasma, respectively. HuAITg mice had HDL cholesterol, human apo A-I, and mouse apo A-I levels of 88 {plus minus} 2, 255 {plus minus} 19, and 16 {plus minus} 2 mg/dl, respectively. Nondenaturing gradient gel electrophoresis revealed control mouse plasma HDL to be primarily monodisperse with a particle diameter of 10.2 nm, whereas HuAITg mouse plasma HDL was polydisperse with particles of diameter 11.4, 10.2, and 8.7 nm, which correspond in size to human HDL1, HDL2, and HDL3, respectively. In vivo turnover studies of HDL labeled with (3H)cholesteryl linoleyl ether and 125I-apo A-I were performed. In control animals, the fractional catabolic rate (FCR) for HDL cholesteryl ester was significantly more than the apo A-I FCR. In the HuAITg mice, the HDL cholesteryl ester FCR was the same as the apo A-I FCR. There were no significant differences between control and HuAITg animals in the sites of tissue removal of HDL cholesteryl ester, with the liver extracting most of the injected radioactivity. Control and HuAITg animals had comparable liver and intestinal cholesterol synthesis and LDL FCR. In conclusion, HuAITg mice have principally human and not mouse apo A-I in their plasma. This apparently causes a change in HDL particle size distribution in the transgenic mice to one resembling the human pattern. The replacement of mouse by human apo A-I also apparently causes the loss of the selective uptake pathway of HDL cholesteryl esters present in control mice.

  20. Self-Assembly and Nanostructures in Organogels Based on a Bolaform Cholesteryl Imide Compound with Conjugated Aromatic Spacer

    Directory of Open Access Journals (Sweden)

    Ti-Feng Jiao


    Full Text Available The self-assembly of small functional molecules into supramolecular structures is a powerful approach toward the development of new nanoscale materials and devices. As a class of self-assembled materials, low weight molecular organic gelators, organized in special nanoarchitectures through specific non-covalent interactions, has become one of the hot topics in soft matter research due to their scientific values and many potential applications. Here, a bolaform cholesteryl imide compound with conjugated aromatic spacer was designed and synthesized. The gelation behaviors in 23 solvents were investigated as efficient low-molecular-mass organic gelator. The experimental results indicated that the morphologies and assembly modes of as-formed organogels can be regulated by changing the kinds of organic solvents. Scanning electron microscopy and atomic force microscopy observations revealed that the gelator molecule self-assemble into different aggregates, from wrinkle and belt to fiber with the change of solvents. Spectral studies indicated that there existed different H-bond formations between imide groups and assembly modes. Finally, some rational assembly modes in organogels were proposed and discussed. The present work may give some insight to the design and character of new organogelators and soft materials with special structures.

  1. Bioreducible Micelles Self-Assembled from Poly(ethylene glycol-Cholesteryl Conjugate As a Drug Delivery Platform

    Directory of Open Access Journals (Sweden)

    Chulsu Baek


    Full Text Available The ability of polymeric micelles to self-assemble into nanosized particles has created interest in their application as potential anticancer drug delivery systems. A poly(ethylene glycol-cholesteryl conjugate (Chol-ss-PEG-ss-Chol connected by cleavable disulfide linkages was synthesized and used as a nanocarrier for in vitro release of doxorubicin (DOX. Owing to its amphiphilic structure, Chol-ss-PEG-ss-Chol was able to self-assemble into micelles with an average diameter 18.6 nm in aqueous solution. The micelles formed large aggregates due to the shedding of the PEG shell through cleavage of disulfide bonds in a reductive environment. The in vitro release studies revealed that Chol-ss-PEG-ss-Chol micelles released 80% and approximately 9% of the encapsulated DOX within 6 h under reductive and non-reductive conditions, respectively. The glutathione (GSH-mediated intracellular drug delivery was investigated in a KB cell line. The cytotoxicity of DOX-loaded micelles indicated a higher cellular anti-proliferative effect against GSH-pretreated than untreated KB cells. Furthermore, confocal laser scanning microscopy (CLSM measurement demonstrated that Chol-ss-PEG-ss-Chol micelles exhibited faster drug release in GSH-pretreated KB cells than untreated KB cells. These results suggest the potential usefulness of disulfide-based polymeric micelles as controlled drug delivery carriers.

  2. Identification and quantification of regioisomeric cholesteryl linoleate hydroperoxides in oxidized human low density lipoprotein and high density lipoprotein. (United States)

    Kenar, J A; Havrilla, C M; Porter, N A; Guyton, J R; Brown, S A; Klemp, K F; Selinger, E


    Oxidation of human LDL is implicated as an initiator of atherosclerosis. Isolated low density lipoprotein (LDL) and high density lipoprotein (HDL2) were exposed to aqueous radicals generated from the thermolabile azo compound 2,2'-azobis(2-amidinopropane) dihydrochloride. The primary nonpolar lipid products formed from the autoxidation of LDL and HDL were the regioisomeric cholesteryl linoleate hydroperoxides. In LDL oxidations, 9- and 13-hydroperoxides with trans,cis conjugated diene were formed as the major oxidation products if endogenous alpha-tocopheral was present in the LDL. After extended oxidation of LDL, at the time when endogenous alpha-tocopherol was consumed, the two trans,cis conjugated diene hydroperoxides began to disappear and the 9- and 13-hydroperoxides with trans,trans conjugated diene appeared. At very long oxidation times, none of the primary products, the conjugated diene hydroperoxides, were present. In HDL2, which has only very low levels of antioxidants, both the 9- and 13-hydroperoxides with trans,cis conjugated diene and the 9- and 13-hydroperoxides with trans,trans conjugated diene were formed at early stages of oxidation. The corresponding alcohols were also formed in the HDL2 oxidations. A mechanistic hypothesis consistent with these observations is presented.

  3. The cholesteryl ester transfer protein (CETP) TaqIB polymorphism in the cholesterol and recurrent events study : no interaction with the response to pravastatin therapy and no effects on cardiovascular outcome: a prospective analysis of the CETP TaqIB polymorphism on cardiovascular outcome and interaction with cholesterol-lowering therapy

    NARCIS (Netherlands)

    de Grooth, Greetje J; Zerba, Kim E; Huang, Shu-Pang; Tsuchihashi, Zenta; Kirchgessner, Todd; Belder, René; Vishnupad, Priya; Hu, Beihong; Klerkx, Anke H E M; Zwinderman, Aeilko H; Jukema, J Wouter; Sacks, Frank M; Kastelein, John J P; Kuivenhoven, Jan Albert


    OBJECTIVES: On the basis of quantitative coronary angiography data, the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism has been postulated to predict the progression of coronary atherosclerosis and response to cholesterol-lowering therapy. BACKGROUND: Cholesteryl ester transfer pr

  4. Hyperspectral-stimulated Raman scattering imaging of cholesteryl ester accumulation: new avenue to diagnosis of human prostate cancer (United States)

    Du, Jun; Wang, Ping; Yue, Shuhua


    Most prostate cancers (PCa) are slowly growing, and only the aggressive ones require early diagnosis and effective treatment. The current standard for PCa diagnosis remains histopathology. Nonetheless, for the differentiation between Gleason score 6 (low-risk PCa), which can be left without treatment, and Gleason score 7 (high-risk PCa), which requires active treatment, the inter-observer discordance can be up to 40%. Our previous study reveals that cholesteryl ester (CE) accumulation induced by PI3K/AKT activation underlies human PCa aggressiveness. However, Raman spectromicroscopy used in this study could only provide compositional information of certain lipid droplets (LDs) selected by the observer, which overlooked cell-to-cell variation and hindered translation to accurate automated diagnosis. Here, we demonstrated quantitative mapping of CE level in human prostate tissues using hyperspectral stimulated Raman scattering (SRS) microscopy that renders compositional information for every pixel in the image. Specifically, hundreds of SRS images at Raman shift between 1620-1800 cm-1 were taken, and multivariate curve resolution algorism was used to retrieve concentration images of acyl C=C bond, sterol C=C bond, and ester C=O bond. Given that the ratio between images of sterol C=C and ester C=O (sterol C=C/C=O) is nonlinearly proportional to CE percentage out of total lipid, we were able to quantitatively map CE level. Our data showed that CE level was significantly greater in high Gleason grade compared to low Gleason grade, and could be a factor that significantly contributed to cancer recurrence. Our study provides an opportunity towards more accurate PCa diagnosis and prediction of aggressiveness.

  5. A Novel Missense Mutation (L296Q) in Cholesteryl Ester Transfer Protein Gene Related to Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    Ke-Qin ZHENG; Si-Zhong ZHANG; Li ZHANG; De-Jia HUANG; Lin-Chuan LIAO; Yi-Ping HOU


    Cholesteryl ester transfer protein (CETP) is a key participant in the reverse transport ofcholesterol from the peripheral tissues to the liver. To understand the role that CETP gene plays in thepathogenesis of coronary heart disease (CHD), the promoter region, all 16 exons and adjacent intronicregions of CETP gene were screened for single nucleotide polymorphisms (SNPs) in 203 CHD patients and209 controls by a combination of PCR, denaturing high performance liquid chromatography (DHPLC),molecular cloning, and DNA sequencing. A novel missense mutation in the CETP gene was identified. Thismutation (L296Q) was a T-to-A conversion at codon 296 of exon 10 which replaced the codon for leucine(CTG) with the codon for glutamine (CAG). Association study revealed that L296Q mutation was associatedwith CHD with a significantly higher mutant allele frequency in the CHD patients than that in the controls (0.160 vs. 0.091,x2= 9.014, P = 0.003), and that the odds ratio for the development of CHD was 1.83 for the296Q allele carriers relative to 296LL homozygotes. Statistical analyses demonstrated that the mutant 296Q allelecarrier patients displayed significantly higher total cholesterol (TC) and low density lipoprotein cholesterol(LDL-C) concentrations than non-carrier patients. The results of the present study suggest that the L296Qmutation is related to CHD, and the identification of new mutations in the CETP gene will afford the oppor-tunity to investigate the relationship between CETP gene and CHD.

  6. A Novel Missense Mutation (L296Q) in Cholesteryl Ester Transfer Protein Gene Related to Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    Ke-QinZHENG; Si-ZhongZHANG; LiZHANG; De-JiaHUANG; Lin-ChuanLIAO; Yi-PingHOU


    Cholesteryl ester transfer protein (CETP) is a key participant in the, reverse transport of cholesterol from the peripheral tissues to the liver. To understand the role that CETP gene plays in the pathogenesis of coronary heart disease (CHD), the promoter region, all 16 exons and adjacent intronic regions of CETP gene were screened for single nucleotide polymorphisms (SNPs) in 203 CHD patients and 209 controls by a combination of PCR, denaturing high performance liquid chromatography (DHPLC),molecular cloning, and DNA sequencing. A novel missense mutation in the CETP geve was identified. This mutation (L296Q) was a T-to-A conversion at codon 296 of exon 10 which replaced the codon for leucine (CTG) with the codon for glutamine (CAG). Association study revealed that L296Q mutation was associated with CHD with a significantly higher mutant allele frequency in the CHD patients than that in the controls (0.160 vs. 0.091,x2=9.014, P=0.003), and that the odds ratio for the development of CHD was 1.83 for the 296Q allele carriers relative to 296LL homozygotes. Statistical analyses demonstrated thai the mutant 296Q allele carrier patients displayed significantly higher total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) concentrations than non-carrier patients. The results of the present study suggest that the L296Q mutation is related to CHD, and the identification of new mutations in the CETP gene will afford the opportunity to investigate the relationship between CETP gene and CHD.

  7. The Relationship Between Genetic Variations of the Cholesteryl Ester Transfer Protein Gene and Coronary Artery Disease in Turkish Subjects (United States)

    Gundogdu, Fuat; Gurlertop, Yekta; Pirim, Ibrahim; Sevimli, Serdar; Dogan, Hasan; Arslan, Sakir; Aksoy, Hulya; Karakelloglu, Sule; Senocak, Huseyin


    Objective Although the relationship between cholesteryl ester transfer protein (CETP) and cholesterol metabolism has been characterized in recent years, the effect of CETP genetic variants associated with coronary artery disease (CAD) is still unclear. Therefore, we investigated the association between CETP gene polymorphism and levels of lipid in patients with CAD. Materials and Methods We conducted a case-control study that included 194 unrelated subjects who underwent coronary angiography for suspected ischemic heart disease. This group was divided into 96 patients with angiographically documented CAD and 98 subjects (individuals matched for age and gender) without angiographically documented CAD (CAD-free subjects), all of whom were studied to examine the genotypic distribution of the CETP gene polymorphism in CAD. Genotyping was performed via polymerase chain reaction. Results Of the 96 patients with CAD, 38 (40%) were B1B1, 42 (44%) B1B2 and 16 (16%) B2B2, compared with the control subjects, of which 35 (36%) were B1B1, 44 (45%) B1B2 and 19 (19%) B2B2. There were no significant differences between patients with CAD and control subjects in the distribution of the CETP gene polymorphism. Patients with the B1B1 genotype had lower high-density lipoprotein-cholesterol (HDL-C) and higher triglyceride (TG) levels than patients with the B2B2 genotype (p<0.05). In addition, among control subjects HDL-C levels were significantly higher in subjects with the B2B2 genotype than in subjects with the B1B1 genotype (p<0.01). Conclusion Our results suggest that genetic variations of the CTEP gene may be responsible for low HDL-C levels but may not be considered as a risk factor for CAD in the Turkish population. PMID:25610061

  8. Facile synthesis of linear-dendritic cholesteryl-poly(epsilon-caprolactone)-b-(L-lysine)(G2) by thiol-ene and azide-alkyne "click" reactions

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Binder, W.H.; Tanner, S.;


    The construction of a linear-dendritic block copolymer consisting of terminal cholesteryl moiety, poly(epsilon-caprolactone), and a second generation L-lysine dendron has been accomplished by the combination of copper(I) catalyzed azide-alkyne and UV-triggered thiol-ene "click" reactions. Ring......-opening polymerization of E-caprolactone initiated by 5-hexyn-1-ol and Mitsunobu coupling with 4-pentenoic acid provide hetero-telechelic poly(epsilon-caprolactone) bearing terminal alkyne and alkene groups. It is then employed in the sequential "click" reactions with the azide-functionalized dendritic wedge...

  9. Synthesis and characterisation of new types of side chain cholesteryl polymers. (United States)

    Wang, Bin; Du, Haiyan; Zhang, Junhua


    A series of cholesterol derivatives have been synthesised via the alkylation reaction of the 3-hydroxyl group with the aliphatic bromide compounds with different chain lengths, namely 3β-alkyloxy-cholesterol. The double bond between the C5 and C6 positions in these cholesterol derivatives was oxidised into epoxy, followed by an epoxy-ring-opening reaction with the treatment with acrylic acid, resulting in a series of 3β-alkyloxy-5α-hydroxy-6β-acryloyloxycholesterol, C(n)OCh (n=1, 2, 4, 6, 8, 10, 12), The acrylate group is connected to the C6 position, which is confirmed by the single crystal structure analysis. The corresponding polymers, PC(n)OCh, were prepared via free radical polymerisation. The structure of monomers and the resulting polymers were characterised with nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC). The thermal properties of PC(n)OCh were studied using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). To determine the secondary structure of polymers, circular dichroism (CD) spectra were performed. It was found that not all monomers produce high-molecular-weight polymers because of steric hindrance. However, all polymers have a helical structure, which can be enhanced by increasing the alkoxy chain length. In addition, increasing the alkoxy chain length decreases the glass transition temperature and increases the decomposition temperature of the polymers.

  10. Noncovalent PEGylation: different effects of dansyl-, L-tryptophan-, phenylbutylamino-, benzyl- and cholesteryl-PEGs on the aggregation of salmon calcitonin and lysozyme. (United States)

    Mueller, Claudia; Capelle, Martinus A H; Seyrek, Emek; Martel, Sophie; Carrupt, Pierre-Alain; Arvinte, Tudor; Borchard, Gerrit


    Protein aggregation is a major instability that can occur during all stages of protein drug production and development. Protein aggregates may compromise the safety and efficacy of the final protein formulation. In this paper, various new excipients [phenylbutylamino-, benzyl-, and cholesteryl-polyethylene glycols (PEGs)] and their use for the reduction of aggregation of salmon calcitonin (sCT) and hen egg-white lysozyme (HEWL) by noncovalent PEGylation are presented. The ability to suppress aggregation of sCT in various buffer systems at a 1:1 molar ratio was assessed by following changes in protein conformation and aggregation state over time. The results are compared with that of dansyl- and L-tryptophan (Trp)-PEGs described in earlier publications. Furthermore, the influence of the different PEG-based excipients on the aggregation of HEWL was measured. HEWL aggregation was completely suppressed in the presence of cholesteryl-PEGs (2 and 5 kDa), whereas deterioration was observed using benzyl-methoxy polyethylene glycols (mPEGs; 2 and 5 kDa). Phenylbutylamino- and Trp-mPEG (2 kDa), as well as dansyl-PEGs of different molecular weight prolonged the lag phase of aggregation and reduced the aggregation velocity of HEWL.

  11. Cultured human astrocytes secrete large cholesteryl ester- andtriglyceride-rich lipoproteins along with endothelial lipase

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Lin; Liu, Yanzhu; Forte, Trudy M.; Chisholm, Jeffrey W.; Parks, John S.; Shachter, Neil S.


    We cultured normal human astrocytes and characterized their secreted lipoproteins. Human astrocytes secreted lipoproteins in the size range of plasma VLDL (Peak 1), LDL (Peak 2), HDL (Peak 3) and a smaller peak (Peak 4), as determined by gel filtration chromatography, nondenaturing gradient gel electrophoresis and transmission electron microscopy. Cholesterol enrichment of astrocytes led to a particular increase in Peak 1. Almost all Peak 2, 3 and 4 cholesterol and most Peak 1 cholesterol was esterified (unlike mouse astrocyte lipoproteins, which exhibited similar peaks but where cholesterol was predominantly non-esterified). Triglycerides were present at about 2/3 the level of cholesterol. LCAT was detected along with two of its activators, apolipoprotein (apo) A-IV and apoC-I. ApoA-I and apoA-II mRNA and protein were absent. ApoJ was present equally in all peaks but apoE was present predominantly in peaks 3 and 4. ApoB was not detected. The electron microscopic appearance of Peak 1 lipoproteins suggested partial lipolysis leading to the detection of a heparin-releasable triglyceride lipase consistent with endothelial lipase. The increased neuronal delivery of lipids from large lipoprotein particles, for which apoE4 has greater affinity than does apoE3, may be a mechanism whereby the apoE {var_epsilon}4 allele contributes to neurodegenerative risk.

  12. Association between cholesteryl ester transfer protein gene polymorphisms and variations in lipid levels in patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    郑克勤; 张思仲; 贺勇; 张立; 张克兰; 黄德嘉; 孙岩


    Background The TaqⅠB, MspⅠ and I405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this study, we investigated the associations between these 3 polymorphisms of CETP gene and variations in plasma lipid and lipoprotein levels in patients with coronary heart disease (CHD).Methods Genomic DNA was extracted from leukocytes of 203 CHD patients and 100 control subjects using the salting out method. Genotyping of the CETP gene was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Statistical analysis was conducted using the SPSS 10.0 software package.Results The distribution of allele and genotype frequencies of the TaqⅠB, MspⅠ, and I405V polymorphisms was similar in the CHD patient group and the control group. The B1B1 genotype of the TaqⅠB polymorphism was associated with significantly higher TC (P=0.039) and LDL-C (P=0.044) levels than the B2B2 genotype in CHD patients, and with significantly higher LDL-C (P=0.034) levels than the B2B2 genotype in controls. Homozygotes of the I405V polymorphism exhibited significantly higher HDL-C levels than VV homozygotes among control subjects (P=0.023). In male CHD patients with unambiguously assigned haplotypes, B2-M2-V/B2-M2-I patients demonstrated significantly higher HDL-C concentrations than B1-M2-V/B1-M2-I (P=0.023) and B1-M2-V/B1-M2-V patients (P=0.047). Conclusions Genetic variations in the CETP gene may account for a significant proportion of the differences in plasma lipid and lipoprotein concentrations among the general population. The B1B1 genotype of the TaqⅠB polymorphism is probably a genetic risk factor for CHD in the study population.

  13. Co-liposomes having anisamide tagged lipid and cholesteryl tryptophan trigger enhanced gene transfection in sigma receptor positive cells. (United States)

    Misra, Santosh K; Moitra, Parikshit; Kondaiah, Paturu; Bhattacharya, Santanu


    Selective gene transfection could be strategy of interest for reducing off-target gene expression and toxicity. In this respect, sigma receptors are found to be over-expressed in many human tumors and liposomal formulations with ability to target these sigma receptors may improve the transfection efficiency to a significant level. To this direction, six novel lipids have been synthesized with different hydrophobic segments such as a long hydrophobic chain or a cholesteryl group and L-tryptophan as the head group. Three of them, Lipid 1, 3 and 5 possessed cationic Me3N(+) moiety at the distal end. In contrast each of the other three Lipid 2, 4 and 6 possessed sigma receptor targeting anisamide group with no cationic charge. Mixing of cationic and anisamide counterparts of the same lipid in a molar ratio of 1:1 produced co-liposomes L-M-1 (Lipid 1+2), L-M-2 (Lipid 3+4) and L-M-3 (Lipid 5+6). These co-liposomes, while keeping the sigma targeting anisamide tag intact, showed good DNA binding and release which were optimized from EB intercalation and gel electrophoresis assays. Inclusion of a zwitterionic, fusogenic natural lipid, DOPE, into the co-liposomes further improved the binding efficiencies of the lipid mixtures with DNA. These co-liposomes having cationic and anisamide lipids and DOPE were highly selective toward sigma positive HEK293 and HEK293T cells compared to the sigma negative HeLa cells. As evidenced from both FACS and luciferase assay, a lipid mixture comprising Lipid 3, 4 and DOPE in a molar ratio of 1:1:1 (L-M-2D1) was the best for transfection of reporter pEGFP-C3 and functional pCEP4-p53 gene plasmids. Anisamide mediated sigma receptor selectivity was further probed by pre-incubating the transfecting cells with lipids possessing anisamide and by quantification of the un-transfected plasmid DNA. Also each formulation was highly non-toxic in the cell lines examined.

  14. Relations Between Atherogenic Index of Plasma, Ratio of Small Dense Low Density Lipoprotein/Lecithin Cholesterol Acyl Transferase and Ratio of Small Dense Low Density Lipoprotein/Cholesteryl Ester Transfer Protein of Controlled and Uncontrolled Type 2 DM

    Directory of Open Access Journals (Sweden)

    Ellis Susanti


    Full Text Available BACKGROUND: Patients with Diabetes Melitus are proven to be prone to atherosclerosis and coronary heart disease, especially type 2 Diabetes Melitus (T2DM patient who have higher risk and mortality for cardiovascular risk factor. The Dyslipidemia condition is very common in T2DM as one of the risk factors. Diabetic dyslipidemia is marked by the increased triglyceride (TG, low HDL cholesterol (HDL-C, and increased small dense LDL and apolipoprotein B. Therefore the aim of this study is to assess the differential and correlation between Atherogenic Index of Plasma (AIP, ratio of small dense low density lipoprotein (sdLDL/lecithin cholesterol acyl transferase (LCAT and ratio of sdLDL/cholesteryl ester transfer protein (CETP of controlled and uncontrolled T2DM. METHODS: This study was observational with cross sectional design. In total of 72 patients with T2DM consist of 36 controlled and 36 uncontrolled, participated in this study. The serum TG, HDL-C, sdLDL, LCAT and CETP were examined in their relationship with to T2DM risk. RESULTS: The results of the study indicate that the AIP (p<0.001 increase controlled and uncontrolled T2DM and the ratio of sdLDL/CETP (p=0.004, odds ratio of AIP was 4 (95% CI: 1.501-10.658 and odds ratio of sdLDL/CETP ratio was 4 (95% CI: 1.501-10.658 in uncontrolled T2DM. CONCLUSIONS: This study showed that the AIP and ratio of small dense LDL/CETP had a significant correlation with the uncontrolled T2DM. The AIP and ratio of small dense LDL/CETP increase was found at the uncontrolled T2DM to be 4 times greater than the controlled T2DM. KEYWORDS: T2DM, atherosclerosis, atherogenic index of plasma, small dense LDL, LCAT, CETP, ratio of sdLDL/LCAT, ratio of sdLDL/CETP.

  15. Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment : individual patient meta-analysis of 13,677 subjects

    NARCIS (Netherlands)

    Boekholdt, S M; Sacks, F M; Jukema, J W; Shepherd, J; Freeman, D J; McMahon, A D; Cambien, F; Nicaud, V; de Grooth, G J; Talmud, P J; Humphries, S E; Miller, G J; Eiriksdottir, G; Gudnason, V; Kauma, H; Kakko, S; Savolainen, M J; Arca, M; Montali, A; Liu, S; Lanz, H J; Zwinderman, A H; Kuivenhoven, J A; Kastelein, J J P


    BACKGROUND: Several studies have reported that the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism is associated with HDL cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD), but the results are inconsistent. In addition, an interaction has been implicated betw

  16. Plasma cholesteryl ester transfer and hepatic lipase activity are related to high-density lipoprotein cholesterol in association with insulin resistance in type 2 diabetic and non-diabetic subjects

    NARCIS (Netherlands)

    Riemens, SC; Van Tol, A; Scheek, LM; Dullaart, RPF


    We evaluated the: hypothesis that plasma cholesteryl ester transfer (CET) and lipase activities are influenced by insulin sensitivity and contribute to the low high-density lipoprotein (HDL) cholesterol observed in type 2 diabetic patients and insulin-resistant non-diabetic subjects. Sixteen type 2

  17. Evaluation of lipids, drug concentration, and safety parameters following cessation of treatment with the cholesteryl ester transfer protein inhibitor anacetrapib in patients with or at high risk for coronary heart disease. (United States)

    Gotto, Antonio M; Cannon, Christopher P; Li, Xiujiang Susie; Vaidya, Sanskruti; Kher, Uma; Brinton, Eliot A; Davidson, Michael; Moon, Jennifer E; Shah, Sukrut; Dansky, Hayes M; Mitchel, Yale; Barter, Philip


    The aim of this study was to assess the effects on lipids and safety during a 12-week reversal period after 18 months of treatment with anacetrapib. The cholesteryl ester transfer protein inhibitor anacetrapib was previously shown to reduce low-density lipoprotein cholesterol by 39.8% (estimated using the Friedewald equation) and increase high-density lipoprotein (HDL) cholesterol by 138.1%, with an acceptable side-effect profile, in patients with or at high risk for coronary heart disease in the Determining the Efficacy and Tolerability of CETP Inhibition With Anacetrapib (DEFINE) trial. A total of 1,398 patients entered the 12-week reversal-phase study, either after completion of the active-treatment phase or after early discontinuation of the study medication. In patients allocated to anacetrapib, placebo-adjusted mean percentage decreases from baseline were observed at 12 weeks off the study drug for Friedewald-calculated low-density lipoprotein cholesterol (18.6%), non-HDL cholesterol (17.6%), and apolipoprotein B (10.2%); placebo-adjusted mean percentage increases were observed for HDL cholesterol (73.0%) and apolipoprotein A-I (24.5%). Residual plasma anacetrapib levels (about 40% of on-treatment apparent steady-state trough levels) were also detected 12 weeks after cessation of anacetrapib. No clinically important elevations in liver enzymes, blood pressure, electrolytes, or adverse experiences were observed during the reversal phase. Preliminary data from a small cohort (n = 30) revealed the presence of low concentrations of anacetrapib in plasma 2.5 to 4 years after the last anacetrapib dose. In conclusion, after the cessation of active treatment, anacetrapib plasma lipid changes and drug levels decreased to approximately 40% of on-treatment trough levels at 12 weeks after dosing, but modest HDL cholesterol elevations and low drug concentrations were still detectable 2 to 4 years after the last dosing.

  18. Alcohol consumption, TaqIB polymorphism of cholesteryl ester transfer protein, high-density lipoprotein cholesterol, and risk of coronary heart disease in men and women

    DEFF Research Database (Denmark)

    Jensen, Majken K; Mukamal, Kenneth J; Overvad, Kim;


    AIMS: To investigate whether a common polymorphism in the cholesteryl ester transfer protein (CETP) gene modifies the relationship of alcohol intake with high-density lipoprotein cholesterol (HDL-C) and risk of coronary heart disease (CHD). METHODS AND RESULTS: Parallel nested case-control studies...... among women [Nurses' Health Study (NHS)] and men [Health Professionals Follow-up Study (HPFS)] where 246 women and 259 men who developed incident CHD were matched to controls (1:2) on age and smoking. The TaqIB variant and alcohol consumption were associated with higher HDL-C, with the most pronounced...... effects of alcohol among B2 carriers. In the NHS we did not find an inverse association between alcohol and CHD in B2 non-carriers (P trend: 0.5), but did among B2 carriers (P trend

  19. Amyloidogenic Properties of a D/N Mutated 12 Amino Acid Fragment of the C-Terminal Domain of the Cholesteryl-Ester Transfer Protein (CETP

    Directory of Open Access Journals (Sweden)

    Victor García-González


    Full Text Available The cholesteryl-ester transfer protein (CETP facilitates the transfer of cholesterol esters and triglycerides between lipoproteins in plasma where the critical site for its function is situated in the C-terminal domain. Our group has previously shown that this domain presents conformational changes in a non-lipid environment when the mutation D470N is introduced. Using a series of peptides derived from this C-terminal domain, the present study shows that these changes favor the induction of a secondary β-structure as characterized by spectroscopic analysis and fluorescence techniques. From this type of secondary structure, the formation of peptide aggregates and fibrillar structures with amyloid characteristics induced cytotoxicity in microglial cells in culture. These supramolecular structures promote cell cytotoxicity through the formation of reactive oxygen species (ROS and change the balance of a series of proteins that control the process of endocytosis, similar to that observed when β-amyloid fibrils are employed. Therefore, a fine balance between the highly dynamic secondary structure of the C-terminal domain of CETP, the net charge, and the physicochemical characteristics of the surrounding microenvironment define the type of secondary structure acquired. Changes in this balance might favor misfolding in this region, which would alter the lipid transfer capacity conducted by CETP, favoring its propensity to substitute its physiological function.

  20. Selective removal of cholesteryl ester in atherosclerotic plaque by nanosecond pulsed laser at 5.75 μm for less-invasive laser angioplasty (United States)

    Ishii, Katsunori; Tsukimoto, Hideki; Hazama, Hisanao; Awazu, Kunio


    Laser angioplasty, for example XeCl excimer laser coronary angioplasty (ELCA), has gained more attention for the treatment of serious stenosis blocked by plaque. Low degrees of thermal damage after ablation of atherosclerotic plaques have been achieved by ELCA. However, the large number of risks associated with the procedure, for example, dissections or perforations of the coronary arteries limits its application. A laser treatment technique with high ablation efficiency but low arterial wall injury is desirable. Mid-infrared laser with a wavelength of 5.75 µm is selectively well absorbed in C=O stretching vibration mode of ester bonds in cholesteryl ester. The purpose of this study is to determine the effectiveness of nanosecond pulsed laser at 5.75 µm irradiation for atherosclerotic plaques. We made a study on the irradiation effect to atherosclerotic plaques in tunica intima in a wet condition. In this study, we used a mid-infrared tunable solid-state laser which is operated by difference-frequency generation, with a wavelength of 5.75 µm, a pulse width of 5 ns and a pulse duration of 10 Hz as a treatment light source, and a thoracic aorta of WHHLMI rabbit as an atherosclerosis model. As a result, less-invasive interaction parameters for removing atherosclerotic plaques were confirmed. This study shows that the nanosecond pulsed laser irradiation at 5.75 µm is a powerful tool for selective and less-invasive treatment of atherosclerotic plaques.

  1. Self-assembled drug delivery systems. Part 8: In vitro/in vivo studies of the nanoassemblies of cholesteryl-phosphonyl gemcitabine. (United States)

    Li, Miao; Qi, Shuo; Jin, Yiguang; Dong, Junxing


    A lipid derivative of gemcitabine (Gem), cholesteryl-phosphonyl gemcitabine (CPNG) was synthesized in this study. The amphiphilicity of CPNG was confirmed using a Langmuir monolayer method. Nanoassemblies were formed when the mixture of CPNG and a long-circulating material, CHS-PEG1500 (9:1, mol/mol) were injected into water. The nanoassemblies could be spherical vesicles according to the transmission electron microscopic images. Their mean size was 71.1 nm and the zeta potential was -17.6 mV. CPNG maintained stable in the weakly acidic and neutral environments although mouse plasma quickly degraded CPNG. The cytotoxicity of the nanoassemblies was 3-6 folds of Gem's cytotoxicity on five human cancer cell lines including 95C, 95D, A549, SW620, PANC-1 probably because of the phosphonyl substitution and amphiphilicity of CPNG. CPNG mainly distributed into the mononuclear macrophage system (including liver and spleen) after bolus intravenous administration of the nanoassemblies into mice though the expected significant long-circulating effect was not shown. The nanoassemblies with the high dose of CPNG showed the statistically higher in vivo anticancer effect than Gem. This study indicates that the N-substituted lipid derivative of Gem and the true long-circulating function are necessary for preparing a successful nanoassembly of Gem.

  2. Helicobacter pylori cholesteryl glucosides interfere with host membrane phase and affect type IV secretion system function during infection in AGS cells. (United States)

    Wang, Hung-Jung; Cheng, Wen-Chi; Cheng, Hsin-Hung; Lai, Chih-Ho; Wang, Wen-Ching


    Helicobacter pylori infection is an aetiological cause of gastric disorders worldwide. H. pylori has been shown to assimilate and convert host cholesterol into cholesteryl glucosides (CGs) by cholesterol-α-glucosyltransferase encoded by capJ. Here, we show that CapJ-deficient (ΔcapJ) H. pylori resulted in greatly reduced type IV secretion system (TFSS)-associated activities, including the hummingbird phenotype of AGS cells, IL-8 production, CagA translocation/phosphorylation and CagA-mediated signalling events. Complementation of the ΔcapJ mutation with wild type cagJ or by adding CGs-containing lysates or exogenous fluorophore-tagged CGs reversed the mutant phenotypes. We also show that the wild-type but not ΔcapJ H. pylori recruited raft-associated components to sites of bacterial attachment. Fluorescence recovery after photobleaching (FRAP) analysis of AGS cells treated with fluorescence-tagged cholesterol/CGs revealed that there was a higher proportion of CGs associated with immobile fractions. CGs-associated membranes were also more resistant to a cold detergent extraction. Thus, we propose that CGs synthesized by H. pylori around host-pathogen contact sites partition in detergent-resistant membranes (DRMs), alters lateral-phase segregation in membrane and reorganizes membrane architecture. These processes together promote the formation of a functional TFSS and H. pylori infection.

  3. The influence of dietary fish oil vs. sunflower oil on the fatty acid composition of plasma cholesteryl-esters in healthy, adult cats. (United States)

    Plantinga, E A; Beynen, A C


    The question addressed was whether the fatty acid composition of plasma cholesteryl esters (CEs) in cats reflects the intake of fatty acids. Diets containing either fish oil or sunflower oil were fed to six healthy, adult cats in a cross-over trial. The dry cat foods contained approximately 18.5% crude fat, of which two-third was in the form of the variable oil. Blood samples were collected at the end of each 4-week feeding period, and the fatty acid composition of plasma CEs and plasma concentrations of lipoproteins were determined. Consumption of the diet with fish oil was associated with significantly greater proportions of eicosapentaenoic acid, arachidonic acid, alpha-linolenic acid, oleic acid, palmitic acid and myristic acid in plasma CEs. The intake of fish oil instead of sunflower oil reduced the percentage of linoleic acid in CEs. The plasma concentrations of total cholesterol, high-density lipoprotein cholesterol, phospholipids and triglycerides were not affected by fish oil vs. sunflower oil feeding.

  4. 氧化低密度脂蛋白诱导主动脉平滑肌细胞胆固醇酯聚集和凋%Oxidized-LDL Leads to Cholesteryl Ester Accumulation and A poptosis in Porcine Aortic Smooth Muscle Cells

    Institute of Scientific and Technical Information of China (English)

    袁中华; 杨永宗; 杨小毅


    Both cellular cholesterol metabolism imbalance and apoptosis are related to th e development of atherosclerosis. To investigate the relationship between the ce llular cholesterol metabolism and apoptosis, the porcine aortic smooth muscle ce lls were cultured with medium 199 containing 15 mg/L oxidized low density lipo protein (Ox-LDL) for 72 h, the ratio of cellular cholesteryl ester to total cholesterol increased from 26.2% to 64.1%, and Ox-LDL induced accumulation o f cellular ch olesteryl ester in a concentration dependent manner in the cells. It indicated t hat the vascular smooth muscle cells had transformed to foam cells. In addition, cells incubated with oxidized low density lipoprotein had characteristic of apo ptosis, as determined by fluorescence microscope, laser scanning confocal micros cope and flow cytometry. From this findings, it was speculated that the inducti on of apoptosis may be related to the raise of the ratio of cellular cholesteryl este r to total cholesterol besides oxidation of low density lipoprotein in vascular smooth muscle cells.%细胞内胆固醇代谢的失衡和细胞凋亡都与动脉粥样硬化的发生有关.为了研究两者之间的关系,我们把猪的主动脉平滑肌细胞与15 mg/L氧化低密度脂蛋白共同孵育 72 h,发现细胞内胆固醇酯与总胆固醇的比值由26.2%增加到64.1%,并且细胞内胆固醇酯的积聚有剂量依赖关系,表明细胞已经转化为平滑肌源性的泡沫细胞.另外,使用荧光显微镜、激光共聚焦显微镜和流式细胞仪分别发现,与氧化低密度脂蛋白共孵育的细胞有典型的凋亡形态改变.从实验可以推测,由氧化低密度脂蛋白诱导的平滑肌细胞凋亡,除了低密度脂蛋白氧化的因素外,也可能与细胞内胆固醇酯与总胆固醇的比值升高有关.

  5. Cholesterol increases kinetic, energetic, and mechanical stability of the human β2-adrenergic receptor

    DEFF Research Database (Denmark)

    Zocher, Michael; Zhang, Cheng; Rasmussen, Søren Gøgsig Faarup;


    the kinetic, energetic, and mechanical stability of almost every structural segment at sufficient magnitude to alter the structure and functional relationship of β(2)AR. One exception was the structural core segment of β(2)AR, which establishes multiple ligand binding sites, and its properties were...... to quantify the mechanical strength and flexibility, conformational variability, and kinetic and energetic stability of structural segments stabilizing the human β(2)-adrenergic receptor (β(2)AR) in the absence and presence of the cholesterol analog cholesteryl hemisuccinate (CHS). CHS considerably increased...

  6. Taq1B Polymorphism of Cholesteryl Ester Transfer Protein (CETP) and Its Effects on the Serum Lipid Levels in Metabolic Syndrome Patients. (United States)

    Maroufi, Nazila Fathi; Farzaneh, Khadijeh; Alibabrdel, Mahdi; Zarei, Leila; Cheraghi, Omid; Soltani, Sina; Montazersaheb, Soheila; Akbarzadeh, Maryam; Nouri, Mohammad


    The metabolic syndrome (MetS) is one of the most important risk factors for type 2 diabetes and cardiovascular disease. This syndrome is characterized by abdominal obesity, hypertension, insulin resistance, and dyslipidemia. The plasma origin of Cholesteryl ester transfer protein (CETP) is responsible for transferring cholesterol esters from high-density lipoprotein particles to apolipoprotein B containing lipoproteins compartment. We conducted this study to investigate the association between CETP gene Taq1B (rs708272) polymorphism in the metabolic syndrome among Iranian subjects. A sample size of 200 patients diagnosed with MetS together with 200 healthy donors as control were enrolled in this study. The investigation of polymorphism was performed by the use of polymerase chain reaction and restriction fragment length polymorphism analysis. To determine the relationship between polymorphism and lipid profile, we measured lipids and CETP concentration in metabolic syndrome and control subjects. Genotype distribution and allelic frequencies of polymorphism were determined and compared in both groups. Our findings showed that all clinical and biochemical characteristics in patients differed from the control group. The results showed that genotype and allele frequency of the Taq1B polymorphism was not significantly different between two groups. Instinctively, CETP was significantly higher in metabolic syndrome (1.64 ± 0.32 µg/ml) than in control (1.53 ± 0.34 µg/ml). A low level of CETP was found in blood of B2B2 typified genotype. In spite of Taq1B polymorphism on ester transfer protein concentration, no direct correlation was found between this polymorphism and metabolic syndrome.

  7. Associations of Cholesteryl Ester Transfer Protein TaqIB Polymorphism with the Composite Ischemic Cardiovascular Disease Risk and HDL-C Concentrations: A Meta-Analysis (United States)

    Guo, Shu-xia; Yao, Ming-hong; Ding, Yu-song; Zhang, Jing-yu; Yan, Yi-zhong; Liu, Jia-ming; Zhang, Mei; Rui, Dong-sheng; Niu, Qiang; He, Jia; Guo, Heng; Ma, Ru-lin


    Background: Previous studies have evaluated the associations between the cholesteryl ester transfer protein (CETP) TaqIB polymorphism (rs708272), the risk of developing composite ischemic cardiovascular disease (CVD) and the concentration of high-density lipoprotein cholesterol (HDL-C), but results remain controversial. The objective of this study was to investigate whether a relationship exists between these factors. Methods: We conducted a meta-analysis of available studies to clarify the associations of the CETP TaqIB polymorphism with HDL-C concentration and the composite ischemic CVD risk in both Asians and Caucasians. All statistical analyses were done with Stata 12.0. Results: Through utilization of the Cochrane Library, Embase, PubMed, Web of Science, Springer, China Science and Technology Journal Database, China National Knowledge Infrastructure, Google Scholar, and Baidu Library, a total of 45 studies from 44 papers with 20,866 cases and 21,298 controls were combined showing a significant association between the CETP TaqIB variant and composite ischemic CVD risk. Carriers of allele TaqIB-B1 were found to have a higher risk of composite ischemic CVD than non-carriers: OR = 1.15, 95% CI = 1.09–1.21, p < 0.001. Meanwhile, 28 studies with 23,959 subjects were included in the association between the CETP TaqIB polymorphism and the concentration of HDL-C. Results suggested that carriers of the B1B1 genotype had lower concentrations of HDL-C than those of the B2B2 genotype: SMD = 0.50, 95% CI = 0.36–0.65, p < 0.001. Conclusions: The synthesis of available evidence demonstrates that the CETP TaqIB polymorphism protects against composite ischemic CVD risk and is associated with a higher HDL-C concentration in both Asians and Caucasians. PMID:27608031

  8. Associations of Cholesteryl Ester Transfer Protein TaqIB Polymorphism with the Composite Ischemic Cardiovascular Disease Risk and HDL-C Concentrations: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Shu-xia Guo


    Full Text Available Background: Previous studies have evaluated the associations between the cholesteryl ester transfer protein (CETP TaqIB polymorphism (rs708272, the risk of developing composite ischemic cardiovascular disease (CVD and the concentration of high-density lipoprotein cholesterol (HDL-C, but results remain controversial. The objective of this study was to investigate whether a relationship exists between these factors. Methods: We conducted a meta-analysis of available studies to clarify the associations of the CETP TaqIB polymorphism with HDL-C concentration and the composite ischemic CVD risk in both Asians and Caucasians. All statistical analyses were done with Stata 12.0. Results: Through utilization of the Cochrane Library, Embase, PubMed, Web of Science, Springer, China Science and Technology Journal Database, China National Knowledge Infrastructure, Google Scholar, and Baidu Library, a total of 45 studies from 44 papers with 20,866 cases and 21,298 controls were combined showing a significant association between the CETP TaqIB variant and composite ischemic CVD risk. Carriers of allele TaqIB-B1 were found to have a higher risk of composite ischemic CVD than non-carriers: OR = 1.15, 95% CI = 1.09–1.21, p < 0.001. Meanwhile, 28 studies with 23,959 subjects were included in the association between the CETP TaqIB polymorphism and the concentration of HDL-C. Results suggested that carriers of the B1B1 genotype had lower concentrations of HDL-C than those of the B2B2 genotype: SMD = 0.50, 95% CI = 0.36–0.65, p < 0.001. Conclusions: The synthesis of available evidence demonstrates that the CETP TaqIB polymorphism protects against composite ischemic CVD risk and is associated with a higher HDL-C concentration in both Asians and Caucasians.

  9. Cholesteryl ester transfer protein inhibitors in coronary heart disease: Validated comparative QSAR modeling of N, N-disubstituted trifluoro-3-amino-2-propanols. (United States)

    Mondal, Chanchal; Halder, Amit Kumar; Adhikari, Nilanjan; Jha, Tarun


    Cholesteryl ester transfer protein (CETP) converts high density lipoprotein cholesterol to low density lipoproteins. It is a promising target for treatment of coronary heart disease. Two dimensional quantitative structure activity relationship (2D-QSAR), hologram QSAR (HQSAR) studies and comparative molecular field analysis (CoMFA) as well as comparative molecular similarity analysis (CoMSIA) were performed on 104 CETP inhibitors. The statistical qualities of generated models were justified by internal and external validation, i.e., q(2) and R(2)pred respectively. The best 2D-QSAR model was obtained with q(2) and R(2)pred values of 0.794 and 0.796 respectively. The 2D-QSAR study suggests that unsaturation, branching and van der Waals volumes may play important roles. The HQSAR model showed q(2) and R(2)pred values of 0.628 and 0.550 respectively. Similarly, CoMFA model showed q(2) and R(2)pred values of 0.707 and 0.755 respectively whereas CoMSIA model was obtained with q(2) and R(2)pred values of 0.696 and 0.703 respectively. CoMFA and CoMSIA studies indicate that steric factors are important at substituted phenoxy and tetrafluoroethoxy groups whereas electropositive factors play important role at difluoromethyl group. The results of 3D-QSAR studies validate those of 2D-QSAR and HQSAR studies as well as the earlier observed SAR data. Current work may help to develop better CETP inhibitors.

  10. Design of chiral dimesogens containing cholesteryl groups; formation of new molecular organizations and their application to molecular photonics. (United States)

    Mallia, V Ajay; Tamaoki, Nobuyuki


    Photoresponsive liquid crystals and organogels are finding increasing application in information technology and photonics. In this tutorial review, the authors describe how weak intermolecular interactions facilitate molecular organization of cholesterol-containing dimesogens to form such materials. Design considerations and photoresponsive properties of both organogels and glassy liquid crystals are discussed and their applications to molecular photonics highlighted. The review will be of value to readers interested in the development of new materials which respond to the different properties of light.

  11. Otters Increasing - Threats Increasing

    Directory of Open Access Journals (Sweden)

    Andreas Kranz


    Full Text Available In some parts of Central Europe populations of otters are apparently increasing. Until recently, no research was being conducted on the ecology of otters in mainly artificial habitats like fish farms. Otters are not only a new source of conflict requiring species management, but appear once again threatened by illegal hunting. Austria is dealing with this problem using compensation for otter damage, electric fencing and translocation of problem otters. Despite a rise in illegal killing, Austria does not formally recognise this as a threat.

  12. Antibody responses against NY-ESO-1 and HER2 antigens in patients vaccinated with combinations of cholesteryl pullulan (CHP)-NY-ESO-1 and CHP-HER2 with OK-432. (United States)

    Aoki, Masatoshi; Ueda, Shugo; Nishikawa, Hiroyoshi; Kitano, Shigehisa; Hirayama, Michiko; Ikeda, Hiroaki; Toyoda, Hideki; Tanaka, Kyosuke; Kanai, Michiyuki; Takabayashi, Arimichi; Imai, Hiroshi; Shiraishi, Taizo; Sato, Eiichi; Wada, Hisashi; Nakayama, Eiichi; Takei, Yoshiyuki; Katayama, Naoyuki; Shiku, Hiroshi; Kageyama, Shinichi


    Combination vaccines of the NY-ESO-1 protein complexed with cholesteryl pullulan (CHP), CHP-NY-ESO-1, and the truncated 146HER2 protein with CHP, CHP-HER2, were subcutaneously administered with the immuno-adjuvant OK-432 to eight esophageal cancer patients. Vaccination was well-tolerated. NY-ESO-1- and HER2-specific antibody responses were analyzed using the patients' sera and samples from previous single CHP-NY-ESO-1 or CHP-HER2 vaccine trial. The responses to NY-ESO-1 in the combination vaccine study were comparable to the single vaccine. For responses to HER2, there were fewer antibody responses in the combination vaccines. Although there were marked individual variations in the antibody responses to the NY-ESO-1 and HER2 antigens, the reaction patterns to these antigens were comparable within each patient. Antibodies to OK-432 were not augmented. Protein cancer vaccines targeting multiple antigens are feasible.

  13. ACAT1 deficiency increases cholesterol synthesis in mouse peritoneal macrophages. (United States)

    Dove, Dwayne E; Su, Yan Ru; Swift, Larry L; Linton, MacRae F; Fazio, Sergio


    Acyl-coenzyme A:cholesterol acyltransferase (ACAT) esterifies free cholesterol and stores cholesteryl esters in lipid droplets. Macrophage ACAT1 deficiency results in increased atherosclerotic lesion area in hyperlipidemic mice via disrupted cholesterol efflux, increased lipoprotein uptake, accumulation of intracellular vesicles, and accelerated apoptosis. The objective of this study was to determine whether lipid synthesis is affected by ACAT1. The synthesis, esterification, and efflux of new cholesterol were measured in peritoneal macrophages from ACAT1(-/-) mice. Cholesterol synthesis was increased by 134% (p=0.001) in ACAT1(-/-) macrophages compared to wildtype macrophages. Increased synthesis resulted in a proportional increase in the efflux of newly synthesized cholesterol. Although the esterification of new cholesterol was reduced by 93% (pSREBP1a mRNA was increased 6-fold in ACAT1(-/-) macrophages compared to wildtype macrophages, suggesting an up-regulation of cholesterol and fatty acid synthesis in ACAT1(-/-) macrophages. Increased cholesterol synthesis and up-regulation of SREBP in ACAT1(-/-) macrophages suggests that ACAT1 affects the regulation of lipid metabolism in macrophages. This change in cholesterol homeostasis may contribute to the atherogenic potential of ACAT1(-/-) macrophages.

  14. Walnut-enriched diet increases the association of LDL from hypercholesterolemic men with human HepG2 cells. (United States)

    Muñoz, S; Merlos, M; Zambón, D; Rodríguez, C; Sabaté, J; Ros, E; Laguna, J C


    In a randomized, cross-over feeding trial involving 10 men with polygenic hypercholesterolemia, a control, Mediterranean-type cholesterol-lowering diet, and a diet of similar composition in which walnuts replaced approximately 35% of energy from unsaturated fat, were given for 6 weeks each. Compared with the control diet, the walnut diet reduced serum total and LDL cholesterol by 4.2% (P = 0.176), and 6.0% (P = 0.087), respectively. No changes were observed in HDL cholesterol, triglycerides, and apolipoprotein A-I levels or in the relative proportion of protein, triglycerides, phospholipids, and cholesteryl esters in LDL particles. The apolipoprotein B level declined in parallel with LDL cholesterol (6.0% reduction). Whole LDL, particularly the triglyceride fraction, was enriched in polyunsaturated fatty acids from walnuts (linoleic and alpha-linolenic acids). In comparison with LDL obtained during the control diet, LDL obtained during the walnut diet showed a 50% increase in association rates to the LDL receptor in human hepatoma HepG2 cells. LDL uptake by HepG2 cells was correlated with alpha-linolenic acid content of the triglyceride plus cholesteryl ester fractions of LDL particles (r(2) = 0.42, P < 0.05). Changes in the quantity and quality of LDL lipid fatty acids after a walnut-enriched diet facilitate receptor-mediated LDL clearance and may contribute to the cholesterol-lowering effect of walnut consumption.

  15. TaqI B1/B2 and -629A/C cholesteryl ester transfer protein (CETP gene polymorphisms and their association with CETP activity and high-density lipoprotein cholesterol levels in a Tehranian population. Part of the Tehran Lipid and Glucose Study (TLGS

    Directory of Open Access Journals (Sweden)

    Maryam S Daneshpour


    Full Text Available We examined the cholesteryl ester transfer protein (CETP gene TaqI intron 1 B1/B2 polymorphism and the -629A/C CETP promoter polymorphism in respect to high-density lipoprotein cholesterol (HDL-C in a healthy Iranian population taken from the Tehran Lipid and Glucose Study (TLGS. The relationship between CETP activity and HDL-C level was also determined along with body mass index, blood pressure and tobacco smoking status. PCR-RFLP used to amplify a segment of the CETP intron 1 TaqI (B2/B1 polymorphism from 1021 individuals and we selected 345 individuals from the lowest, middle and highest HDL-C deciles and investigated the -629A/C polymorphism. We also evaluated the CETP activity of 103 of these individuals, each with at least one homozygous allele. The presence of the TaqI B2 and -629A/C A alleles were significantly associated with increased HDL-C levels (B2B2 = 1.19 ± 0.31 mmolL-1 vs. B1B1 = 1.01 ± 0.2 mmol L-1 for p < 0.001; AA = 1.15 ± 0.41 mmol L-1 vs. CC = 0.95 ± 0.28 mmol L-1 for p < 0.001 and decreased the CETP activity (B1B1 = 67.8 ± 8.9 pmol L-1 vs. B2B2 = 62.6 ± 9.6 pmol L-1 for p < 0.01; CC = 68.6 ± 8.4 pmol L-1 vs. AA = 62.7 ± 9.7 pmol L-1 for p < 0.002. The frequencies were 0.382 for the TaqI B2 allele and 0.462 for the -629A/C A allele, with linkage disequilibrium analysis giving D = 0.0965 and D' = 0.4695. We demonstrated that the TaqI B1 and B2 alleles and the -629A/C A and C alleles were in linkage disequilibrium in our population and that there was a significant association between the B2 and A alleles and high HDL-C levels and low CETP activity. Linkage disequilibrium between the TaqI A and B2 alleles also detected.

  16. Unique cellular events occurring during the initial interaction of macrophages with matrix-retained or methylated aggregated low density lipoprotein (LDL). Prolonged cell-surface contact during which ldl-cholesteryl ester hydrolysis exceeds ldl protein degradation. (United States)

    Buton, X; Mamdouh, Z; Ghosh, R; Du, H; Kuriakose, G; Beatini, N; Grabowski, G A; Maxfield, F R; Tabas, I


    A critical event in atherogenesis is the interaction of arterial wall macrophages with subendothelial lipoproteins. Although most studies have investigated this interaction by incubating cultured macrophages with monomeric lipoproteins dissolved in media, arterial wall macrophages encounter lipoproteins that are mostly bound to subendothelial extracellular matrix, and these lipoproteins are often aggregated or fused. Herein, we utilize a specialized cell-culture system to study the initial interaction of macrophages with aggregated low density lipoprotein (LDL) bound to extracellular matrix. The aggregated LDL remains extracellular for a relatively prolonged period of time and becomes lodged in invaginations in the surface of the macrophages. As expected, the degradation of the protein moiety of the LDL was very slow. Remarkably, however, hydrolysis of the cholesteryl ester (CE) moiety of the LDL was 3-7-fold higher than that of the protein moiety, in stark contrast to the situation with receptor-mediated endocytosis of acetyl-LDL. Similar results were obtained using another experimental system in which the degradation of aggregated LDL protein was delayed by LDL methylation rather than by retention on matrix. Additional experiments indicated the following properties of this interaction: (a) LDL-CE hydrolysis is catalyzed by lysosomal acid lipase; (b) neither scavenger receptors nor the LDL receptor appear necessary for the excess LDL-CE hydrolysis; and (c) LDL-CE hydrolysis in this system is resistant to cellular potassium depletion, which further distinguishes this process from receptor-mediated endocytosis. In summary, experimental systems specifically designed to mimic the in vivo interaction of arterial wall macrophages with subendothelial lipoproteins have demonstrated an initial period of prolonged cell-surface contact in which CE hydrolysis exceeds protein degradation.

  17. An apoA-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration

    Directory of Open Access Journals (Sweden)

    Xun Chen, Charlotte Burton, Xuelei Song, Lesley Mcnamara, Annunziata Langella, Simona Cianetti, Ching H. Chang, Jun Wang


    Full Text Available Lecithin cholesterol acyltransferase (LCAT plays a key role in the reverse cholesterol transport (RCT process by converting cholesterol to cholesteryl ester to form mature HDL particles, which in turn deliver cholesterol back to the liver for excretion and catabolism. HDL levels in human plasma are negatively correlated with cardiovascular risk and HDL functions are believed to be more important in atheroprotection. This study investigates whether and how D-4F, an apolipoprotein A-I (apoA-I mimetic peptide, influences LCAT activity in the completion of the RCT process. We demonstrated that the apparent rate constant value of the LCAT enzyme reaction gives a measure of LCAT activity and determined the effects of free metals and a reducing agent on LCAT activity, showing an inhibition hierarchy of Zn2+>Mg2+>Ca2+ and no inhibition with β-mercaptoethanol up to 10 mM. We reconstituted nano-disc particles using apoA-I or D-4F with phospholipids. These particles elicited good activity in vitro in the stimulation of cholesterol efflux from macrophages through the ATP-binding cassette transporter A1 (ABCA1. With these particles we studied the LCAT activity and demonstrated that D-4F did not activate LCAT in vitro. Furthermore, we have done in vivo experiments with apoE-null mice and demonstrated that D-4F (20 mg/kg body weight, once daily subcutaneously increased LCAT activity and HDL level as well as apoA-I concentration at 72 hours post initial dosing. Finally, we have established a correlation between HDL concentration and LCAT activity in the D-4F treated mice.

  18. Price increase

    CERN Multimedia


    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced, as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  19. Price increase

    CERN Multimedia


    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  20. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism. (United States)

    Briand, François; Mayoux, Eric; Brousseau, Emmanuel; Burr, Noémie; Urbain, Isabelle; Costard, Clément; Mark, Michael; Sulpice, Thierry


    In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly reduced fasting blood glucose by 18%, with significant increase in fasting plasma LDL cholesterol, free fatty acids, and total ketone bodies by 25, 49, and 116%, respectively. In fasting conditions, glycogen hepatic levels were further reduced by 84% with empagliflozin, while 3-hydroxy-3-methylglutaryl-CoA reductase activity and total cholesterol hepatic levels were 31 and 10% higher, respectively (both P catabolism of (3)H-cholesteryl oleate-labeled LDL injected intravenously by 20%, indicating that empagliflozin raises LDL levels through reduced catabolism. Unexpectedly, empagliflozin also reduced intestinal cholesterol absorption in vivo, which led to a significant increase in LDL- and macrophage-derived cholesterol fecal excretion (both P < 0.05 vs. vehicle). These data suggest that empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels. Interestingly, empagliflozin also reduces intestinal cholesterol absorption, which in turn promotes LDL- and macrophage-derived cholesterol fecal excretion.

  1. A Study on Correlation between Cholesteryl Ester Transfer Protein and Coronary Heart Disease%胆固醇酯转运蛋白水平与冠心病患者血脂指标的相关性

    Institute of Scientific and Technical Information of China (English)

    刘祎; 刘寅; 高静


    Objective To investigate the effect of cholesteryl ester transfer protein (CETP) on lipid parameters in patients with coronary heart disease (CHD). Methods Five hundred and fifty-five cases were divided into CHD group (n= 430) and control group (n=120) according to the result of coronary angiography (CAG). The plasma levels of CETP, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1(ApoA1), apolipoprotein B (ApoB) and ApoA1/ApoB were measured and analyzed respectively in two groups. Results The values of HDL-C, ApoA1 and ApoAl/ApoB were significantly lower in CHD group compared with those of control group (P < 0.01). There was no significant difference in the level of CETP hetween two groups, hut the level of CETP was negatively correlated with the levels of HDL-C and ApoAl (r,= -0.141 and r,= -0.165 ,P < 0.05). The multivari-ate logistic regression analysis showed that CETP level was not independent risk factors of CHD.Conclusion Although CETP was not influencing factors of coronary heart disease, this study provided clinical data for regulating hlood lipids and treatment of coronary heart disease hy the intervention of CETP.%目的 探讨血浆胆固醇酯转运蛋白(CETP)对冠心病(CHD)患者相关血脂指标的影响.方法 行冠状动脉造影的患者550例,根据冠状动脉造影结果分为CHD组(n=430)和正常组(n=120).测定2组血浆CETP、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)及ApoA1/ApoB水平.结果 CHD组患者血浆中HDL-C、ApoA1及ApoA1/ApoB的水平显著低于正常组(P < 0.01);CETP水平在CHD组与正常组间差异无统计学意义,CETP水平与HDL-C和ApoA1值呈负相关(rs分别为-0.141和-0.165,P < 0.05);多因素Logistic回归分析显示,CETP不是CHD的独立影响因素.结论 CETP虽然不是冠心病的

  2. Modulation of plasma fibrinogen levels by medication

    NARCIS (Netherlands)

    Maat, M.P.M. de; Kodex, M.; Kastelein, J.J.P.


    Elevated plasma fibrinogen levels represent an increased risk for cardiac events. This has enhanced the interest in identifying agents that can normalize elevated plasma fibrinogen levels. Agents that have this capacity are the lipid lowering fibric acid derivatives (e.g. ciprofibrate) and the plate

  3. Serum cholesteryl ester n-3 fatty acid analysis by high performance liquid chromatography%高效液相色谱测定血清胆固醇酯n-3脂肪酸指数方法的建立

    Institute of Scientific and Technical Information of China (English)

    崔瑞芳; 董军; 周伟燕; 国汉邦; 李红霞; 满永; 王抒; 陈文祥


    Objective To develop an HPLC method for the measurement of n-3 fatty acid index of serum cholesteryl esters.Methods Serum triglycerides were hydrolyzed with ethanolic sodium hydroxide and cholesteryl esters (CEs) were extracted with hexane.The extracted CEs were analyzed by reversed phase HPLC with a UV detection at 205 nm.Cholesteryl eicosapentaenoate and docosahexaenoate ( major n-3 fatty acid cholesteryl esters) were identified by liquid chromatography-tandem mass spectrometry and cholesterol in each CE fraction was measured.Peak areas of CEs were corrected for cholesterol and CE n-3 index was calculated using the corrected peak area and expressed as the percentage of n-3 fatty acid CEs in total CEs.Results The HPLC analysis can be finished in 6 minutes.Triglycerides which interfere with the determination of n-3 fatty acid index, were hydrolyzed with ethanolic sodium hydroxide (4 mol/L) in 30 seconds.The within-run and total CVs for CE n-3 index averaged 0.66% and 0.90%, respectively.CE n-3 indexes of 70 volunteers and 36 coronary heart disease patients apparently healthy subjects and patients with coronary heart disease in Beijing Hospital appeared to be positively skewed and leptokurtic distribution ( skewness = 1.25, kurtosis = 1.70 ).The median of n-3 indices were 0.98% ( 0.37% - 2.40% ).The logarithm of n-3 index appeared to be normal distribution and the average is 0.003 7% with standard deviations of 0.15.The distribution of n-3 indices of gender groups was similar with the total.The medians of females and males were 1.08% (0.60% -2.40%) and 0.95% (0.37% -2.11%) respectively, and the former were significantly higher than the latter( t = - 3.021, P = 0.003 ).Conclusion A new method for the measurement of n-3 index of serum cholesteryl esters by HPLC has been established.It is simple and precise and can be used in predicting cardiovascular diseases risks and monitoring dietary intake of n-3 fatty acids.%目的 建立一种HPLC测定血清胆固醇酯n-3

  4. Grape Polyphenols Increase the Activity of HDL Enzymes in Old and Obese Rats

    Directory of Open Access Journals (Sweden)

    Andriy L. Zagayko


    Full Text Available HDL particles are protein-rich particles that act as a vehicle for reverse cholesterol transport from tissues to the liver. The purpose of this study was to investigate age-dependent changes in the functional activity of HDL and the effect of high-energy diet on this index, as well as to correct it under the influence of grape polyphenols from “Enoant” obtained from Vitis vinifera grapes. We observed the age-dependent composition changes in HDL particle. It was shown that total lipids and triacylglycerol (TG levels were higher in 24-month-old animals. In obese rats, HDL total lipids and TG levels were higher in 24-month-old than in the 3-month-old and 12-month-old groups but did not differ from 24-month-old group. The plasma HDL paraoxonase (PON and lecithin:cholesterol acyltransferase (LCAT activity levels were decreased in old-aged rats, and cholesteryl ester transfer protein (CETP activity was higher in old rats. Keeping 12-month-old animals on high-fructose diet completely leveled the age differences in the data that have been measured between 12-month-old and 24-month-old rats. After “Enoant” administration, an increase of HDL PON and LCAT activity levels and a reduction of CETP activity were found in 24-month-old and obese rats.

  5. Preparation of New Amphiphilic Liquid-Crystal Diblock Copolymers Bearing Side-on Cholesteryl Mesogen and Their Self-aggregation%具有侧挂胆固醇液晶元的两亲嵌段功能大分子的合成及自组装研究

    Institute of Scientific and Technical Information of China (English)

    胡方振; 陈圣典; 李慧; 孙景景; 盛瑞隆; 罗挺; 曹阿民


    采用可逆加成-断裂链转移(RAFT)聚合法,合成了系列具有刚性疏水胆固醇液晶元的聚甲基丙烯酸甘油酯-嵌段-聚甲基丙烯酸亚己基胆固醇酯(PGMA-b-PMA6Chol)两亲嵌段功能大分子.运用核磁共振(NMR)和凝胶渗透色谱(GPC)表征了其化学结构及分子量,并对其热性质、液晶相结构及相转变行为分别运用热台偏振光显微镜(POM)、热重分析仪(TGA)、示差扫描量热仪(DSC)和二维小角X射线散射(2D-SAXS)表征.采用纳米沉淀法研究了所得嵌段大分子的溶液自组装,动态光散射(DLS)和扫描电子显微镜(SEM)的研究发现溶液自组装聚集体为尺寸0.7~2.0rn的球形结构,其中含有较高刚性链段质量比例的嵌段大分子组装形成开口中空结构的聚集体,且其尺寸随着溶液温度的升高减小,呈现可逆温度变化响应性.结果表明刚性疏水胆固醇液晶单元和具有多羟基结构的亲水性甲基丙烯酸甘油酯的嵌段共聚可以调控该类嵌段大分子自组装及溶液聚集体形貌.%Amphiphilic block copolymers bearing rigid hydrophobic liquid crystal mesogen have recently attracted broad interests since they could spontaneously self-assemble into functional objects at the micron and/or nanometer scales, and these soft matters bearing high-order hierarchical structures have potential applications in micro-reactors, advanced catalysts, biosensors, drug delivery, biotechnology and so forth. In this work, we designed and successfully prepared a new series of amphiphilic liquid crystal poly(glyceryl methaciylate)-b-poly(6-cholesteryloxyhexyl methacrylate) (PGMA-b-PMA6Chol) with hydrophobic PMA6Chol block bearing end-on cholesteryl mesogen through sequential controlled reversible addition-fragmentation chain transfer polymerization (RAFT) and successive removal of ketal protection groups. Then, their structures and comonomer composition were examined by nuclear magnetic resonance (NMR) and gel permeation

  6. Genetic variants in CETP increase risk of intracerebral hemorrhage (United States)

    Falcone, Guido J.; Phuah, Chia‐Ling; Radmanesh, Farid; Brouwers, H. Bart; Battey, Thomas W. K.; Biffi, Alessandro; Peloso, Gina M.; Liu, Dajiang J.; Ayres, Alison M.; Goldstein, Joshua N.; Viswanathan, Anand; Greenberg, Steven M.; Selim, Magdy; Meschia, James F.; Brown, Devin L.; Worrall, Bradford B.; Silliman, Scott L.; Tirschwell, David L.; Flaherty, Matthew L.; Kraft, Peter; Jagiella, Jeremiasz M.; Schmidt, Helena; Hansen, Björn M.; Jimenez‐Conde, Jordi; Giralt‐Steinhauer, Eva; Elosua, Roberto; Cuadrado‐Godia, Elisa; Soriano, Carolina; van Nieuwenhuizen, Koen M.; Klijn, Catharina J. M.; Rannikmae, Kristiina; Samarasekera, Neshika; Salman, Rustam Al‐Shahi; Sudlow, Catherine L.; Deary, Ian J.; Morotti, Andrea; Pezzini, Alessandro; Pera, Joanna; Urbanik, Andrzej; Pichler, Alexander; Enzinger, Christian; Norrving, Bo; Montaner, Joan; Fernandez‐Cadenas, Israel; Delgado, Pilar; Roquer, Jaume; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Kidwell, Chelsea S.; Kittner, Steven J.; Waddy, Salina P.; Langefeld, Carl D.; Abecasis, Goncalo; Willer, Cristen J.; Kathiresan, Sekar; Woo, Daniel; Rosand, Jonathan


    Objective In observational epidemiologic studies, higher plasma high‐density lipoprotein cholesterol (HDL‐C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL‐C; as such, medicines that inhibit CETP and raise HDL‐C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL‐C also increase risk for ICH. Methods We performed 2 candidate‐gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL‐C as well as ICH risk. Results Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10−4) with no heterogeneity across studies (I 2 = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL‐C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10−6). Interpretation Genetic variants in CETP associated with increased HDL‐C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL‐raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730–740 PMID:27717122

  7. Preparation and Anti-Tumor Effect of Oridonin Loaded Cholesteryl Formate-Graft Chitosan Copolymer Nano-micelles%冬凌草甲素/胆固醇甲酰-壳聚糖共聚物纳米胶束的制备及其体外抗肿瘤作用

    Institute of Scientific and Technical Information of China (English)

    赵永星; 赵阳; 张振中; 张雪晓; 孙倩


    目的 制备冬凌草甲素/胆固醇甲酰-壳聚糖共聚物(ORI/CF-CS)纳米胶束并研究其体外抗肿瘤活性.方法 采用酰胺化反应合成胆固醇甲酰-壳聚糖共聚物(CF-CS);以CF-CS为载体材料制备ORI/CF-CS纳米胶束,并测定其载药量、包封率、形态、粒径和ξ电位;MTT法测定其对宫颈癌Hela肿瘤细胞的细胞毒作用.结果 ORI/CF-CS纳米胶束载药量为9.16%,包封率为48.83%,粒径控制在68.10~113.8 nm内,ξ电位为-34.97~-29.19 mV,体外释药缓慢;ORI/CF-CS纳米胶束对Hela肿瘤细胞的细胞毒作用优于冬凌草甲素溶液,且IC50值比冬凌草甲素溶液低约3倍.结论 CF-CS是冬凌草甲素的优良载体,且可提高其抗Hela肿瘤细胞的活性.%OBJECTIVE To prepare oridonin-loaded cholesteryl formate-graft chitosan copolymer (abbreviated as ORI/CF-CS) nano-micelles and study the in vitro anti-tumor activity. METHODS Cholesteryl formate-graft chitosan copolymer (abbreviated as CF-CS) was synthesized via amidation reaction. ORI/CF-CS nano-micelles were prepared by evaporating and characterized by drug loading content,entrapment efficiency, morphology, particle size,and £ potential. MTT test were applied to assess the cytotoxicity of ORI/CF-CS nano-micelles on Hela cells line. RESULTS The prepared ORI/CF-CS nanomicelles had loading content of 9.16% andentrapment efficiency of 48. 83% ,small size range of 68.10 -113. 8 nm,{j potential range of -34. 97----29. 19 mV,and slow releasein vitro. The cytotoxicity of ORI/CF-CS nanomicelles was stronger than that of oridonin solution. IC,,, value of ORI/CF-CS nanomicelles was about 3 times lower,than those of oridonin solution. CONCLUSION CF-CS nano-micelles might be used as potential carriers of oridonin for cancer therapy.

  8. Increased methionine sulfoxide content of apoA-I in type 1 diabetes. (United States)

    Brock, Jonathan W C; Jenkins, Alicia J; Lyons, Timothy J; Klein, Richard L; Yim, Eunsil; Lopes-Virella, Maria; Carter, Rickey E; Thorpe, Suzanne R; Baynes, John W


    Cardiovascular disease is a major cause of morbidity and premature mortality in diabetes. HDL plays an important role in limiting vascular damage by removing cholesterol and cholesteryl ester hydroperoxides from oxidized low density lipoprotein and foam cells. Methionine (Met) residues in apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, reduce peroxides in HDL lipids, forming methionine sulfoxide [Met(O)]. We examined the extent and sites of Met(O) formation in apoA-I of HDL isolated from plasma of healthy control and type 1 diabetic subjects to assess apoA-I exposure to lipid peroxides and the status of oxidative stress in the vascular compartment in diabetes. Three tryptic peptides of apoA-I contain Met residues: Q(84)-M(86)-K(88), W(108)-M(112)-R(116), and L(144)-M(148)-R(149). These peptides and their Met(O) analogs were identified and quantified by mass spectrometry. Relative to controls, Met(O) formation was significantly increased at all three locations (Met(86), Met(112), and Met(148)) in diabetic patients. The increase in Met(O) in the diabetic group did not correlate with other biomarkers of oxidative stress, such as N(epsilon)-malondialdehyde-lysine or N(epsilon)-(carboxymethyl)lysine, in plasma or lipoproteins. The higher Met(O) content in apoA-I from diabetic patients is consistent with increased levels of lipid peroxidation products in plasma in diabetes. Using the methods developed here, future studies can address the relationship between Met(O) in apoA-I and the risk, development, or progression of the vascular complications of diabetes.

  9. Effects of step-wise increases in dietary carbohydrate on circulating saturated Fatty acids and palmitoleic Acid in adults with metabolic syndrome. (United States)

    Volk, Brittanie M; Kunces, Laura J; Freidenreich, Daniel J; Kupchak, Brian R; Saenz, Catherine; Artistizabal, Juan C; Fernandez, Maria Luz; Bruno, Richard S; Maresh, Carl M; Kraemer, William J; Phinney, Stephen D; Volek, Jeff S


    Recent meta-analyses have found no association between heart disease and dietary saturated fat; however, higher proportions of plasma saturated fatty acids (SFA) predict greater risk for developing type-2 diabetes and heart disease. These observations suggest a disconnect between dietary saturated fat and plasma SFA, but few controlled feeding studies have specifically examined how varying saturated fat intake across a broad range affects circulating SFA levels. Sixteen adults with metabolic syndrome (age 44.9±9.9 yr, BMI 37.9±6.3 kg/m2) were fed six 3-wk diets that progressively increased carbohydrate (from 47 to 346 g/day) with concomitant decreases in total and saturated fat. Despite a distinct increase in saturated fat intake from baseline to the low-carbohydrate diet (46 to 84 g/day), and then a gradual decrease in saturated fat to 32 g/day at the highest carbohydrate phase, there were no significant changes in the proportion of total SFA in any plasma lipid fractions. Whereas plasma saturated fat remained relatively stable, the proportion of palmitoleic acid in plasma triglyceride and cholesteryl ester was significantly and uniformly reduced as carbohydrate intake decreased, and then gradually increased as dietary carbohydrate was re-introduced. The results show that dietary and plasma saturated fat are not related, and that increasing dietary carbohydrate across a range of intakes promotes incremental increases in plasma palmitoleic acid, a biomarker consistently associated with adverse health outcomes.

  10. Increasing Mobility Confidence (United States)

    ... Español In Your Area NPF Shop Increasing Mobility Confidence To increase your confidence moving, you have to move! Make Text Smaller ... It might seem counterintuitive, but to increase your confidence moving, you have to move! Build physical activity ...

  11. Effect of increased

    NARCIS (Netherlands)

    Carreira , C.; Heldal, M.; Bratbak, G.


    Atmospheric carbon dioxide (CO2) has increased since the pre-industrial period and is predicted to continue to increase throughout the twenty-first century. The ocean is a sink for atmospheric CO2 and increased CO2 concentration will change the carbonate equilibrium of seawater and result in lower c

  12. Increasingly minimal bias routing

    Energy Technology Data Exchange (ETDEWEB)

    Bataineh, Abdulla; Court, Thomas; Roweth, Duncan


    A system and algorithm configured to generate diversity at the traffic source so that packets are uniformly distributed over all of the available paths, but to increase the likelihood of taking a minimal path with each hop the packet takes. This is achieved by configuring routing biases so as to prefer non-minimal paths at the injection point, but increasingly prefer minimal paths as the packet proceeds, referred to herein as Increasing Minimal Bias (IMB).

  13. Increasing SLEDed Linac Gradient

    Energy Technology Data Exchange (ETDEWEB)

    Farkas, Zoltan D


    This note will show how to increase the SLED [1] gradient by varying Q{sub e}, the external Q of the SLED cavity, by increasing its Q{sub 0} and by increasing the compression ratio. If varying the external Q is to be effective, then the copper losses should be small so that Q{sub 0} >> Q{sub e}. Methods of varying Q{sub e} will be indicated but no experimental data will be presented. If we increase the klystron pulse width from 3.5 to 5 {micro}S and increase Q{sub 0} from the present 100000 to 300000, then the gradient increases by 19% and the beam energy increases from 50 to 60 GeV. This note will also discuss SLED operation at 11424 MHz, the NLC frequency. Without Q{sub e} switching, using SLED at 11424 MHz increases the SLAC gradient from 21 MV/m to 34 MV/m, and at the same repetition rate, uses about 1/5 of rf average power. If we also double the compression ratio, we reach 47 MV/m and over 100 GeV beam energy.

  14. Echium Oil Reduces Plasma Triglycerides by Increasing Intravascular Lipolysis in apoB100-Only Low Density Lipoprotein (LDL Receptor Knockout Mice

    Directory of Open Access Journals (Sweden)

    John S. Parks


    Full Text Available Echium oil (EO, which is enriched in SDA (18:4 n-3, reduces plasma triglyceride (TG concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%, EO (10% EO + 10% PO, or FO (10% FO + 10% PO. Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL particle size was ordered: PO (63 ± 4 nm > EO (55 ± 3 nm > FO (40 ± 2 nm. Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  15. Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice. (United States)

    Forrest, Lolita M; Lough, Christopher M; Chung, Soonkyu; Boudyguina, Elena Y; Gebre, Abraham K; Smith, Thomas L; Colvin, Perry L; Parks, John S


    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  16. Increasing Public Library Productivity. (United States)

    Samuelson, Howard


    Suggests ways of improving productivity for public libraries faced with increased accountability, dwindling revenues, and continuing inflation. Techniques described include work simplification, work analysis, improved management, and employee motivation. (RAA)

  17. Increased intracranial pressure (United States)

    ... patient's bedside in an emergency room or hospital. Primary care doctors may sometimes spot early symptoms of increased intracranial pressure such as headache, seizures, or other nervous system problems. An MRI ...

  18. Meeting increased demand. (United States)

    Blair, Andrew


    New Zealand is a little country with a little economy but with a population that's rapidly aging. New Zealand's population is only 4.3 million people. It's GDP is only $US58.6 billion (2002). New Zealand's expenditure on health as a percentage of GDP is not out of line with that of other countries. As a nation we have been increasing expenditure on health over recent years. In 1990 we spent 7% of GDP on health. In 1995 that increased to 7.65% and is now 8.3%. However, in per capita terms our expenditure on health does not compare so well with like countries. The size of New Zealand's economy is restricting what our country spends on health. Health is already the second highest demand on the New Zealand tax dollar. The tolerance of New Zealanders would be challenged if a Government attempted to increase taxes further to meet the growing demands for expenditure on health, but at the same time the population's expectations are increasing. This is the challenging situation we face today. What lies ahead? Like all industrialized countries New Zealand is facing an aging population. The population below age 40 is decreasing, but it is increasing significantly over that age. 16% of the population is currently aged over 60. By 2051 this proportion will almost double to just over 31%. Coupled with the aging population is increased awareness and expectations, as access to options for treatment and technology becomes readily accessible to the population through such media as the internet. The extent of the impact of the aging population can be clearly represented by focusing on one specialty such as orthopaedics. The New Zealand Orthopaecic Association undertook a study in July 2003 which concluded (among other things) that as a result of the projected aging of the population, over the next 50 years: Musculo-skeletal operations will increase by over 30%. The number of hip replacements will nearly double. The incidence of osteoporosis will increase by a massive 201%. The number

  19. Exploding Increase of Population

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.H. [Sunmoon University, Chonan (Korea)


    Until 1650, the population of the world did not increase properly. According to studies of the demography, the annual increase rate of the world population during 2500 years, from 850 B.C. to 1650 A.D., was just 0.07%. Currently, however, the world population, which has exceptionally rapidly increased from 1900, is more than 6 billion as of 2000. After World War II, especially, the increase rate of the population has risen to about 1.8%, so we can use the word, explosion of the population. The explosion of the population accompanies the increase of energy consumption. The energy production of every year cannot sufficiently meet the energy demand, so we can face the grand energy crisis someday. The date might be a someday after 2020. According to the future forecasting of Shell, one of the majors, the peak of oil supply will be between 2015 and 2020. Unless the alternative energy is developed, the whole world will suffer the serious oil crisis.

  20. Increased urinary orosomucoid excretion

    DEFF Research Database (Denmark)

    Christiansen, M S; Iversen, K; Larsen, C T;


    , impaired left ventricular function and endothelial dysfunction in patients with type 2 diabetes. MATERIAL AND METHODS: We performed a cross-sectional study of 41 patients with type 2 diabetes (17 patients with normal UOER and 24 with increased UOER) with no history of cardiovascular disease and 21 healthy...

  1. Increasing mobile radiography productivity. (United States)

    Wong, Edward; Lung, Ngan Tsz; Ng, Kris; Jeor, Patrick


    Mobile radiography using computed radiography (CR) cassettes is a common equipment combination with a workflow bottleneck limited by location of CR readers. Advent of direct digital radiography (DDR) mobile x-ray machines removes this limitation by immediate image review and quality control. Through the use of key performance indicators (KPIs), the increase in efficiency can be quantified.

  2. Increasing income inequality

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Poulsen, Odile

    In recent decades most developed countries have experienced an increase in income inequality. In this paper, we use an equilibrium search framework to shed additional light on what is causing an income distribution to change. The major benefit of the model is that it can accommodate shocks...... to the skill composition in the market, employee bargaining power and productivity. Further, when our model is subjected to skill-upgrading and changes in employee bargaining power, it is capable of predicting the recent changes observed in the Danish income distribution. In addition, the model emphasizes...... that shocks to the employees' relative productivity, i.e., skill-biased technological change, are unlikely to have caused the increase in income inequality....

  3. Pemex increasing offshore activity

    Energy Technology Data Exchange (ETDEWEB)

    Beachy, D.


    Although austere by boom-year standards, Mexico's National Energy Program for 1984-1988 calls for forty wildcats and 90 to 144 development wells off the coast, primarily in the prolific Campeche Bay area. Platform additions will include nine drilling platforms, each for twelve wells, and eight eight platforms to drill injection wells. Additionally, 7 production, 6 accomodation, 6 linkage and 8 compression platforms and 13 tetrapods will be installed. The main objectives of the plan are energy self-sufficiency through the turn of the century, and energy diversification, savings and productivity. The most controversial portion of Mexico's energy program is that calling for nuclear energy development. The energy program lists three basic goals in hydrocarbon production: continuing research on better techniques of secondary recovery; increasing capacity for refining primary and secondary crude products and improving production of heavy crudes; and increasing storage capacity and installing pipelines capable of carrying a greater volume of crude.

  4. Market Expects Demand Increase

    Institute of Scientific and Technical Information of China (English)


    In the recent releasing Textile Industry Invigorating Plan,"givingattention to both domestlc and overseas markets"is put into a keyposition.Under a series policies,such as increasing the tax rebaterate for textile and garment exports,and granting loan for SME,thefurther development of this industry is expectative.Otherwise,weshould know that it costs time for demand driving.This need ourpatients.The only questionis how much time we have to wait.

  5. Increasing student success (United States)

    Stewart, Gay; Stewart, John


    A more scientifically literate society benefits all STEM disciplines, as well as society as a whole. It is best realized by better serving all undergraduate STEM students. In better-serving all students, a physics department also benefits. The University of Arkansas, Fayetteville physics department has seen a drastic change in number of majors, the number of students active in research and the number of graduates pursuing graduate work, while also increasing the number of majors who decide to teach. Prior to our involvement with the Physics Teacher Education Coalition, graduation rates had increased by more than a factor of 4 in 4 years. After the increased efforts when we became a part of PhysTEC ( our graduation numbers doubled again. Specific attention to class policy to impact student learning in our introductory courses and strong preparation of the graduate teaching assistants, and quality advising were our primary areas of emphasis. What worked to build these numbers and strengthen these resources at Arkansas will be discussed. This work was supported in part by the National Science Foundation and through the Physics Teacher Education Coalition.

  6. Alarming increase in refugees. (United States)


    Over the past decade and half there has been an alarming worldwide increase in refugees. The total rose form 2.8 million in 1976 to 8.2 million in 1980, to 17.3 million in 1990. Africa's refugees rose from 1.2 million in 1976 to 5.6 million in 1990. Asia's increase over this period was much more rapid--from a mere 180,000 to 8 million. In the Americas the numbers more than trebled, from 770,000 to 2.7 million. Europe was the smallest increase, from 570,000 to 894,000. International law defines a refugee as someone outside of their own country, who has a well-founded fear of persecution because of their political or religious beliefs or ethnic origin, and who cannot turn to their own country for protection. Most refugees are genuine by this definition. The increase reflects, in part, fallout from the cold war. Ethiopia, Mozambique and Angola accounted for almost 1/2 of Africa's refugees; Afghanistan alone for 3/4 of Asia's total. They fled, for the most part, from 1 poor country into another, where they added to shortages of land and fuelwood, and intensified environmental pressure. Malawi, 1 of the poorest countries in the world, is sheltering perhaps as many as 750,000 refugees from the war in Mozambique. But among these refugees--especially among those who turned to the rich countries for asylum--were an increasing number of people who were not suffering political persecution. Driven out of their homes by the collapse of their environment or economic despair, and ready to take any means to get across borders, they are a new category: economic and environmental refugees. The most spectacular attempts hit the television screens: the Vietnamese boat people, ships festooned with Albanians. Behind the headlines there was a growing tide of asylum seekers. The numbers rose 10-fold in Germany from 1983 to 1990. In Switzerland they multiplied by 4 times. In Europe, as a whole, they grew from 71,000 in 1983 to an estimated 550,000 in 1990. In 1990 the numbers threatened to

  7. Increasing Inflationary Pressure

    Institute of Scientific and Technical Information of China (English)

    Guo Yan


    @@ China's CPI rose to 8.7 percent in February after hitting 7.1 percent in January,creating a 12-year high,the National Bureau of Statistics said.The figure exceeded market expectations,as the Bank of China,the country's secondlargest lender,had predicted a rise of only 8.3 percent.The Consumer Price Index (CPI)is the main gauge of inflation,andthe high CPI over the last two months has put pressure on the government to take action to curb the price increases,and added even more diffculty to the task of reining in this year's inflation rate.


    Institute of Scientific and Technical Information of China (English)

    Mu Xueping


    @@ After half a year's gestation and adjustment, the State Administration of Taxation finally set new tax rate of petroleum resources. Notification issued by the Ministry of Finance and the State Administration of Taxation said the petroleum resources tax standard would be lifted nationwide, after the tax rate adjustment, tax on crude oil would be increased to RMB 14-30 yuan per ton and that on natural gas to RMB 7-15 yuan per thousand cubic meters. The new tax rate has been effective nationwide since July 1.

  9. Increasing Childhood Influenza Vaccination (United States)

    Nowalk, Mary Patricia; Lin, Chyongchiou J.; Hannibal, Kristin; Reis, Evelyn C.; Gallik, Gregory; Moehling, Krissy K.; Huang, Hsin-Hui; Allred, Norma J.; Wolfson, David H.; Zimmerman, Richard K.


    Background Since the 2008 inception of universal childhood influenza vaccination, national rates have risen more dramatically among younger children than older children and reported rates across racial/ethnic groups are inconsistent. Interventions may be needed to address age and racial disparities to achieve the recommended childhood influenza vaccination target of 70%. Purpose To evaluate an intervention to increase childhood influenza vaccination across age and racial groups. Methods In 2011–2012, 20 primary care practices treating children were randomly assigned to Intervention and Control arms of a cluster randomized controlled trial to increase childhood influenza vaccination uptake using a toolkit and other strategies including early delivery of donated vaccine, in-service staff meetings, and publicity. Results The average vaccination differences from pre-intervention to the intervention year were significantly larger in the Intervention arm (n=10 practices) than the Control arm (n=10 practices), for children aged 2–8 years (10.2 percentage points (pct pts) Intervention vs 3.6 pct pts Control) and 9–18 years (11.1 pct pts Intervention vs 4.3 pct pts Control, p<0.05), for non-white children (16.7 pct pts Intervention vs 4.6 pct pts Control, p<0.001), and overall (9.9 pct pts Intervention vs 4.2 pct pts Control, p<0.01). In multi-level modeling that accounted for person- and practice-level variables and the interactions among age, race and intervention, the likelihood of vaccination increased with younger age group (6–23 months), white race, commercial insurance, the practice’s pre-intervention vaccination rate, and being in the Intervention arm. Estimates of the interaction terms indicated that the intervention increased the likelihood of vaccination for non-white children in all age groups and white children aged 9–18 years. Conclusions A multi-strategy intervention that includes a practice improvement toolkit can significantly improve influenza

  10. Elenoside increases intestinal motility

    Institute of Scientific and Technical Information of China (English)

    E Navarro; SJ Alonso; R Navarro; J Trujillo; E Jorge


    AIM: To study the effects of elenoside, an arylnaphthalene lignan from Justicia hyssopifolia, on gastrointestinal motility in vivo and in vitro in rats.METHODS: Routine in vivo experimental assessments were catharsis index, water percentage of boluses,intestinal transit, and codeine antagonism. The groups included were vehicle control (propylene glycol-ethanolplant oil-tween 80), elenoside (i.p. 25 and 50 mg/kg),cisapride (i.p. 10 mg/kg), and codeine phosphate (intragastric route, 50 mg/kg). In vitro approaches used isolated rat intestinal tissues (duodenum, jejunum, and ileum). The effects of elenoside at concentrations of 3.2× 10-4, 6.4 × 10-4 and 1.2 × 10-3 mol/L, and cisapride at 10-6 mol/L were investigated.RESULTS: Elenoside in vivo produced an increase in the catharsis index and water percentage of boluses and in the percentage of distance traveled by a suspension of activated charcoal. Codeine phosphate antagonized the effect of 25 mg/kg of elenoside. In vitro, elenoside in duodenum, jejunum and ileum produced an initial decrease in the contraction force followed by an increase.Elenoside resulted in decreased intestinal frequency in duodenum, jejunum, and ileum. The in vitro and in vivo effects of elenoside were similar to those produced by cisapride.CONCLUSION: Elenoside is a lignan with an action similar to that of purgative and prokinetics drugs.Elenoside, could be an alternative to cisapride in treatment of gastrointestinal diseases as well as a preventive therapy for the undesirable gastrointestinal effects produced by opioids used for mild to moderate pain.

  11. Intake of up to 3 Eggs per Day Is Associated with Changes in HDL Function and Increased Plasma Antioxidants in Healthy, Young Adults. (United States)

    DiMarco, Diana M; Norris, Gregory H; Millar, Courtney L; Blesso, Christopher N; Fernandez, Maria Luz


    Background: HDL function may be more important than HDL concentration in determining risk for cardiovascular disease. In addition, HDL is a carrier of carotenoids and antioxidant enzymes, which protect HDL and LDL particles against oxidation.Objective: The goal of this study was to determine the impact of consuming 0-3 eggs/d on LDL and HDL particle size, HDL function, and plasma antioxidants in a young, healthy population.Methods: Thirty-eight healthy men and women [age 18-30 y, body mass index (in kg/m(2)) 18.5-29.9] participated in this 14-wk crossover intervention. Subjects underwent a 2-wk washout (0 eggs/d) followed by sequentially increasing intake of 1, 2, and 3 eggs/d for 4 wk each. After each period, fasting blood was collected for analysis of lipoprotein subfractions, plasma apolipoprotein (apo) concentration, lutein and zeaxanthin concentration, and activities of lecithin-cholesterol acyltransferase, cholesteryl ester transfer protein, and paraoxonase-1.Results: Compared with intake of 0 eggs/d, consuming 1-3 eggs/d resulted in increased large-LDL (21-37%) and large-HDL (6-13%) particle concentrations, plasma apoAI (9-15%), and lecithin-cholesterol acyltransferase activity (5-15%) (P HDL function and large-LDL particle concentration; however, intake of 2-3 eggs/d supported greater improvements in HDL function as well as increased plasma carotenoids. Overall, intake of ≤3 eggs/d favored a less atherogenic LDL particle profile, improved HDL function, and increased plasma antioxidants in young, healthy adults. This trial was registered at as NCT02531958.

  12. Increasing Possibilities of Nanosuspension

    Directory of Open Access Journals (Sweden)

    Kumar Bishwajit Sutradhar


    Full Text Available Nowadays, a very large proportion of new drug candidates emerging from drug discovery programmes are water insoluble and thus poorly bioavailable. To avoid this problem, nanotechnology for drug delivery has gained much interest as a way to improve the solubility problems. Nano refers to particles size range of 1–1000 nm. The reduction of drug particles into the submicron range leads to a significant increase in the dissolution rate and therefore enhances bioavailability. Nanosuspensions are part of nanotechnology. This interacts with the body at subcellular (i.e., molecular scales with a high degree of specificity and can be potentially translated into targeted cellular and tissue-specific clinical applications designed to achieve maximal therapeutic efficacy with minimal side effects. Production of drugs as nanosuspensions can be developed for drug delivery systems as an oral formulation and nonoral administration. Here, this review describes the methods of pharmaceutical nanosuspension production including advantages and disadvantages, potential benefits, characterization tests, and pharmaceutical applications in drug delivery.

  13. Increasing orUnderselling ?

    Institute of Scientific and Technical Information of China (English)

    Guo Yan


    The downgrade of sovereignty credit rating of the United States causes new concerns on US treasury bonds.According to the report issued recently by Treasury Ministry of United States,China as the largest oversea holding country of US treasury bonds continues to buy US treasury bonds,with an increase of 5.7 billion US dollars in June,marking the third month in line.Till now,China has US treasury bonds up to a new record of 1,165.5 billion US dollars,which amounts to 26% of the oversea holding US treasury bonds,based on market estimation,followed by Japan (20%),UK (8%),Brazil (5%)and Russia (3%).However,in sharp contrast to China,other countries are underselling us treasury bonds,particularly Russia.Data shows that since October 2010,Russia has been selling US treasury bonds for eight months in line,up to 38% of their holdings.Now Russia only holds 111 billion US dollars of US treasury bond.Why the countries take totally different attitudes towards to US treasury bonds? Tne reporter interviewed the experts from China and Russia for more details.

  14. The effect of the sterol oxygen function on the interaction with phospholipids

    NARCIS (Netherlands)

    Demel, R.A.; Lala, A.K.; Kumari, S.N.; Deenen, L.L.M. van


    The effect of cholesteryl ethers (namely cholesteryl methyl ether, cholesteryl ethyl ether, cholesteryl n-propyl ether, cholesteryl isopropyl ether, cholesteryl butyl ether, cholesteryl methoxymethyl ether, cholesteryl (2′-hydroxy)-3-ethyl ether) and cholesteryl ester (namely cholesteryl acetate) is

  15. Iridoid enriched fraction from Ajuga iva reduce cholesterolemia, triacylglycerolemia and increase the lecithin:cholesterol acyltransferase activity of rats fed a cholesterol-rich diet

    Directory of Open Access Journals (Sweden)

    Marie A. Lacaille-Dubois


    Full Text Available Objective: In this study, we examined the effect of iridoid (I derived from lyophilized aqueous extract of Ajuga iva on serum HDL2 and HDL3 compositions and lecithin:cholesterol acyltransferase (LCAT activity, enzyme responsible for reverse cholesterol transport. Methods: Male Wistar rats (n=24 weighing 120±5 g were fed a diet containing 1% cholesterol-rich diet for 15 days. After this phase, the hypercholesterolemic (HC rats were divided into groups fed the same diet and received or not doses (5, 10 or 15 mg/kg b.w by intraperitoneal injection of iridoid for 15 days. Results: Compared to HC group, serum total cholesterol value was 1.4- and 1.2-fold lower in the I5-HC and I10-HC groups. C-HDL2 and C-HDL3 values were increased in the I5-HC, I10-HC and I15-HC groups (3.2- and 4-, 2.2- and 4.2-, and 3.2- and 8.7-fold, respectively. HDL2 amounts were 4-, 4- and 2.5-fold higher in the I5-HC, I10-HC and I15-HC groups. In HDL3, phospholipids contents were similar, whereas, unesterified cholesterol values were 3.3-, 2.8- and 3-fold higher in the I5-HC, I10-HC and I15-HC groups. In HDL2, cholesteryl esters contents were significantly higher in the groups treated with iridoid (p<0.05. LCAT activity was increased in the I5-HC and I10-HC groups. Conclusion: Treatment with iridoid at doses 5 or 10mg/kg b.w reduce cholesterolemia. These molecules act efficiently on the efflux of cholesterol from peripheral tissues to the liver by increasing LCAT activity. [J Exp Integr Med 2012; 2(1.000: 55-60

  16. Co-administration of a CpG adjuvant (VaxImmune, CPG 7909) with CETP vaccines increased immunogenicity in rabbits and mice. (United States)

    Thomas, Lawrence J; Hammond, Russell A; Forsberg, Eric M; Geoghegan-Barek, Kathleen M; Karalius, Brad H; Marsh, Henry C; Rittershaus, Charles W


    Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that facilitates the transfer of neutral lipids and phospholipids between lipoproteins and contributes to the regulation of the plasma concentration of high density lipoprotein cholesterol (HDL-C). Vaccines have been developed that elicit antibodies that bind to and reduce the lipid transfer function of CETP as a way to increase the plasma concentration of HDL-C and prevent or treat atherosclerosis. This study assessed the immunogenicity of two vaccine peptides. The first, CETi-1, is a dimerized synthetic peptide, including residues 461-476 of human CETP and residues 830-843 of tetanus toxoid, TT(830-843). The second, PADRE-CETP, is a monomeric peptide, in which a PADRE T cell epitope (aK-Cha-VAAWTLKAa) replaces the TT(830-843) T cell epitope of CETi-1. Both peptides were formulated with aluminum-containing adjuvants (Alhydrogel), and tested in mice and rabbits with or without the co-administration of the investigational TLR9 agonist VaxImmune (CPG 7909). In both mice and rabbits, the vaccine peptide utilizing the PADRE T cell epitope elicited stronger anti-CETP antibody responses than the CETi-1 vaccine. Also, co-administration of VaxImmune enhanced the anti-CETP antibody responses to both vaccines. Isotype analysis of the murine anti-CETP antibody response to both vaccines demonstrated a switch from IgG1 to IgG2a upon co-administration of VaxImmune. We conclude that (1) the PADRE T cell epitope is more potent than the TT(830-843) epitope in providing help for the anti-CETP antibody response; and (2) co-administration of VaxImmune with either vaccine increased immunogenicity as measured by antibody response.

  17. High Blood Pressure Increasing Worldwide (United States)

    ... page: High Blood Pressure Increasing Worldwide And health risks may appear even ... of people around the world with elevated or high blood pressure increases, so do the number of deaths linked ...

  18. Does residual force enhancement increase with increasing stretch magnitudes? (United States)

    Hisey, Brandon; Leonard, Tim R; Herzog, Walter


    It is generally accepted that force enhancement in skeletal muscles increases with increasing stretch magnitudes. However, this property has not been tested across supra-physiological stretch magnitudes and different muscle lengths, thus it is not known whether this is a generic property of skeletal muscle, or merely a property that holds for small stretch magnitudes within the physiological range. Six cat soleus muscles were actively stretched with magnitudes varying from 3 to 24 mm at three different parts of the force-length relationship to test the hypothesis that force enhancement increases with increasing stretch magnitude, independent of muscle length. Residual force enhancement increased consistently with stretch amplitudes on the descending limb of the force-length relationship up to a threshold value, after which it reached a plateau. Force enhancement did not increase with stretch amplitude on the ascending limb of the force-length relationship. Passive force enhancement was observed for all test conditions, and paralleled the behavior of the residual force enhancement. Force enhancement increased with stretch magnitude when stretching occurred at lengths where there was natural passive force within the muscle. These results suggest that force enhancement does not increase unconditionally with increasing stretch magnitude, as is generally accepted, and that increasing force enhancement with stretch appears to be tightly linked to that part of the force-length relationship where there is naturally occurring passive force.

  19. Increasing tobacco taxes : A cheap tool to increase public health

    NARCIS (Netherlands)

    van Baal, Pieter H. M.; Brouwer, Werner B. F.; Hoogenveen, Rudolf T.; Feenstra, Talitha L.


    Introduction: Several studies have estimated health effects resulting from tobacco tax increases. However, studies on the cost effectiveness of tobacco taxes are scarce. The aim of this study was to estimate the cost effectiveness of tobacco tax increases from a health care perspective, explicitly c

  20. Korea's 2015 cigarette tax increases. (United States)

    Cherukupalli, Rajeev


    South Korea increased tobacco taxes in 2015 after a 10-year gap. This commentary suggests two lessons for public finance practitioners. Substantive tax increases are crucial to reducing tobacco use; particularly where prices are demonstrably lower and prevalence higher in comparison to other countries ranked similarly on economic development indicators. Second, as a rule of thumb, governments cannot afford to neglect the annual increases that ensure that tobacco taxes do not lose their efficacy over time.

  1. Increasing Access to Special Collections

    Directory of Open Access Journals (Sweden)

    Ricky Erway


    Full Text Available In an environment where we increasingly have access to a collective collection of digitized books, special collections will become increasingly invisible if they are not accessible online. In an era of increasing expectations and decreasing budgets, finding ways to streamline some of our processes is the best way to enable us to do more with less. This report details a number of investigations into how access to special collections can be increased. It includes guidance running the gamut from digitization and rights management to policies and procedures.


    CERN Multimedia


    'DSR', the concession holder of Restaurant no. 2 (bldg. 504 - Meyrin site), has submitted to the Restaurant Supervisory Committee a request to increase certain prices. After close examination, the Committee has established that the proposed increases are compatible with the relevant price indexing mechanisms and other contractual conditions. The new prices will apply as from Monday, June 30, 2003.


    CERN Multimedia


    'AVENANCE', the concession holder of Restaurant no. 3 (bldg. 866 - Prévessin site), has submitted to the Restaurant Supervisory Committee a request to increase its prices. After close examination, the Committee has established that the proposed increases are compatible with the relevant price indexing mechanisms and other contractual conditions. The new prices will apply as from Monday, June 2, 2003.

  4. Assessing and Increasing Physical Activity (United States)

    Van Camp, Carole M.; Hayes, Lynda B.


    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  5. Volatiles Which Increase Magma Viscosity (United States)

    Webb, S.


    The standard model of an erupting volcano is one in which the viscosity of a decompressing magma increases as the volatiles leave the melt structure to form bubbles. It has now been observed that the addition of the "volatiles" P, Cl and F result in an increase in silicate melt viscosity. This observation would mean that the viscosity of selected degassing magmas would decrease rather than increase. Here we look at P, Cl and F as three volatiles which increase viscosity through different structural mechanisms. In all three cases the volatiles increase the viscosity of peralkaline composition melts, but appear to always decrease the viscosity of peraluminous melts. Phosphorus causes the melt to unmix into a Na-P rich phase and a Na-poor silicate phase. Thus as the network modifying Na (or Ca) are removed to the phosphorus-rich melt, the matrix melt viscosity increases. With increasing amounts of added phosphorus (at network modifying Na ~ P) the addition of further phosphorus causes a decrease in viscosity. The addition of chlorine to Fe-free aluminosilicate melts results in an increase in viscosity. NMR data on these glass indicates that the chlorine sits in salt-like structures surrounded by Na and/or Ca. Such structures would remove network-modifying atoms from the melt structure and thus result in an increase in viscosity. The NMR spectra of fluorine-bearing glasses shows that F takes up at least 5 different structural positions in peralkaline composition melts. Three of these positions should result in a decrease in viscosity due to the removal of bridging oxygens. Two of the structural positons of F, however, should result in an increase in viscosity as they require the removal of network-modifying atoms from the melt structure (with one of the structures being that observed for Cl). This would imply that increasing amounts of F might result in an increase in viscosity. This proposed increase in viscosity with increasing F has now been experimentally confirmed.

  6. Increasing Positive Interactive Classroom Behavior (United States)

    Kotcher, Elaine; Doremus, Richard R.


    The question examined in this study was as follows: do teachers increase their positive classroom interactive behaviors as a result of training in systematic classroom observation techniques? (Authors/JA)

  7. Demand for Phenol Increases Steadily

    Institute of Scientific and Technical Information of China (English)


    @@ Dramatic growth in output By the end of 2006 China's capacity to produce phenol had reached more than 600 thousand t/a. The total output was 523 thousand tons in 2006,an increase of 18.1% over 2005.

  8. Demand for SBR Increased Steadily

    Institute of Scientific and Technical Information of China (English)

    Gao Yiwen


    @@ 1 Rapid consumption growth Consumption of styrene-butadiene rubber (SBR) in China was 747 thousand tons in 2006, an increase of 21% over 2005, with faster growth than the average rubber consumption growth.


    CERN Multimedia

    Restaurant Supervisory Committee


    'AVENANCE', the concession holder of Restaurant no. 3 (bldg. 866 - Prévessin site), has submitted to the Restaurant Supervisory Committee a request to increase its prices. After close examination, the Committee has established that the proposed increases are compatible with the relevant price indexing mechanisms and other contractual conditions. The new prices will apply as from Monday, June 3, 2002. Restaurant Supervisory Committee, tel. 77551



    Lööf, Hans; Nabavi, Pardis


    Increased urbanization, global warming and sustainable growth belong to the major contemporary policy challenges. Today cities are home to more than 50% of the world population, the largest 600 urban centers generate about 60% of global GDP, and the agglomerated areas are responsible for 75% of world carbon emissions. The UN estimates that 70% of the world's growing population will live in cities by 2050. At the same time the world population is expected to increase from 7 billion people to 9...

  11. Pulsed electric field increases reproduction. (United States)

    Panagopoulos, Dimitris J


    Purpose To study the effect of pulsed electric field - applied in corona discharge photography - on Drosophila melanogaster reproduction, possible induction of DNA fragmentation, and morphological alterations in the gonads. Materials and methods Animals were exposed to different field intensities (100, 200, 300, and 400 kV/m) during the first 2-5 days of their adult lives, and the effect on reproductive capacity was assessed. DNA fragmentation during early- and mid-oogenesis was investigated by application of the TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay. Sections of follicles after fixation and embedding in resins were observed for possible morphological/developmental abnormalities. Results The field increased reproduction by up to 30% by increasing reproductive capacity in both sexes. The effect increased with increasing field intensities. The rate of increase diminished at the strongest intensities. Slight induction of DNA fragmentation was observed exclusively in the nurse (predominantly) and follicle cells, and exclusively at the two most sensitive developmental stages, i.e., germarium and predominantly stage 7-8. Sections of follicles from exposed females at stages of early and mid-oogennesis other than germarium and stages 7-8 did not reveal abnormalities. Conclusions (1) The specific type of electric field may represent a mild stress factor, inducing DNA fragmentation and cell death in a small percentage of gametes, triggering the reaction of the animal's reproductive system to increase the rate of gametogenesis in order to compensate the loss of a small number of gametes. (2) The nurse cells are the most sensitive from all three types of egg chamber cells. (3) The mid-oogenesis checkpoint (stage 7-8) is more sensitive to this field than the early oogenesis one (germarium) in contrast to microwave exposure. (4) Possible therapeutic applications, or applications in increasing fertility, should be investigated.

  12. Increased chromosome radiosensitivity during pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Ricoul, Michelle; Sabatier, Laure; Dutrillaux, Bernard [Commissariat a l`Energie Atomique, Laboratoire de Radiobiologie et Oncologie, DRR, DSV, Fontenay aux roses (France)


    It was necessary to consider the risks of exposure of pregnant women, not only in relation to the child, but also in relation to their own hypersensitivity. We have demonstrated that pregnancy increases radiosensitivity of chromosome in the mouse at the end of gestation. This is of importance since it may have implications on radioprotection of pregnant women and give experimental guidelines to the problems of hypersensitivity to drugs and cancer aggravation during pregnancy. Blood obtained from women at various times of pregnancy was exposed to ionizing radiations. By comparison to non-pregnant women, an increase in chromosome breakage was observed in metaphases from lymphocytes, after short-term culture in the presence of the serum of the same donor. Immediately after delivery, this increase in radiosensitivity disappeared. In a prospective study, serial analyses showed a very strong correlation between the amount of pregnancy hormones, progesterone in particular, and the increase in radiosensitivity. Pregnant women may have an increased sensitivity to ionizing radiation during the second half of their pregnancy. This study provides the first evidence in human that radiosensitivity may vary in relation to physiological conditions.

  13. Increasing work-time influence

    DEFF Research Database (Denmark)

    Nabe-Nielsen, Kirsten; Garde, Anne Helene; Aust, Birgit


    This quasi-experimental study investigated how an intervention aiming at increasing eldercare workers' influence on their working hours affected the flexibility, variability, regularity and predictability of the working hours. We used baseline (n = 296) and follow-up (n = 274) questionnaire data......-operation with colleagues. In subgroup B and C, the participants ended up discussing the potential consequences of more work-time influence without actually implementing any changes. PRACTITIONER SUMMARY: Employee work-time influence may buffer the adverse effects of shift work. However, our intervention study suggested...... that while increasing the individual flexibility, increasing work-time influence may also result in decreased regularity of the working hours and less continuity in the care of clients and co-operation with colleagues....

  14. PMR Composites Of Increased Toughness (United States)

    Vannucci, Raymond D.; Bowles, Kenneth J.


    Toughness increased without sacrificing processability or hot strength. Resin composition provides best overall balance of composite toughness and retention of mechanical properties at 600 degree F (316 degree C) with processability obtained by substituting 20 mole percent of diamine used in PMR-15 resins with diamine containing twice number of flexible phenyl connecting groups.

  15. Increasing Positive Interactive Classroom Behavior. (United States)

    Kotcher, Elaine; Doremus, Richard R.

    During the spring of 1972 training workshops for 88 elementary and secondary teachers of the Great Neck Public Schools held to examine four hypotheses: 1) workshops in training teachers to observe classroom behavior would significantly increase these same teachers' positive classroom interactive behaviors consisting of teacher, pupil-pupil,…

  16. Increased Challenge with the Elderly. (United States)

    Wilson, Helen

    Research has shown that too little stress or stimulation can increase health risks. To determine the effectiveness of mild stimulation on the depression levels and feelings of self-worth of the elderly, 24 withdrawn nursing home residents participated in a non-judgemental 6-month art expression group. Half the group were assigned to a control…

  17. Increasing Enrollment through Benefit Segmentation. (United States)

    Goodnow, Betty


    The applicability of benefit segmentation, a market research technique which groups people according to benefits expected from a program offering, was tested at the College of DuPage. Preferences and demographic characteristics were analyzed and program improvements adopted, increasing enrollment by 20 percent. (Author/SK)

  18. Yohimbine increases human salivary secretion. (United States)

    Chatelut, E; Rispail, Y; Berlan, M; Montastruc, J L


    The effect of oral yohimbine (14 mg) on salivary secretion was evaluated in healthy volunteers. Yohimbine significantly increased salivary secretion when compared with placebo. This effect was significant from 60 min until 180 min after administration under our experimental conditions. Yohimbine (or alpha 2-adrenoceptor blocking agents) could have a potential interest in the treatment of dry mouths. PMID:2789932

  19. Demand for ink Increases Rapidly

    Institute of Scientific and Technical Information of China (English)

    Song Guiqin


    @@ Output increased steadily China's ink sector has developed rapidlyin recent years.According to the NationalBureau of Statistics of China.China's ink output was 347.9 thousand tons in 2006,anincrease of 15.1% over 2005.

  20. Increase voted to NSF Budget (United States)

    Richman, Barbara T.

    The Subcommittee on Science, Research, and Technology of the House Committee on Science and Technology voted by a narrow margin on March 10 to increase the National Science Foundation (NSF) budget authorization by $30 million, pushing the total budget to $1099.5 million. The increase is targeted solely for science and engineering education (see table). Although the total for research and related activities in NSF remained the same as in President Reagan's budget request, the subcommittee shifted funds among directorates, including an $8.9 million decrease from the budget of the Directorate for Astronomical, Atmospheric, Earth, and Ocean Sciences (AAEO). The subcommittee action also calls for $1.6 million to be allocated to United States participation in the International Institute for Applied Systems Analysis (NASA).

  1. Increasing Accuracy in Environmental Measurements (United States)

    Jacksier, Tracey; Fernandes, Adelino; Matthew, Matt; Lehmann, Horst


    Human activity is increasing the concentrations of green house gases (GHG) in the atmosphere which results in temperature increases. High precision is a key requirement of atmospheric measurements to study the global carbon cycle and its effect on climate change. Natural air containing stable isotopes are used in GHG monitoring to calibrate analytical equipment. This presentation will examine the natural air and isotopic mixture preparation process, for both molecular and isotopic concentrations, for a range of components and delta values. The role of precisely characterized source material will be presented. Analysis of individual cylinders within multiple batches will be presented to demonstrate the ability to dynamically fill multiple cylinders containing identical compositions without isotopic fractionation. Additional emphasis will focus on the ability to adjust isotope ratios to more closely bracket sample types without the reliance on combusting naturally occurring materials, thereby improving analytical accuracy.

  2. Production Increased with Higher Prices

    Institute of Scientific and Technical Information of China (English)

    Feng shiling


    @@ In the first quarter of 2007, China's petroleum and chemical industry remained up trend in production.Among the 66 types of petrochemical products that have been tracked by CPCIA (China Petroleum and Chemical Industry Association), the output of 58, types increased compared with the same period of 2006, accounting for 87.9% of the total, and the output of 19 types, in particular, grew by over20%, accounting for 28.8%.

  3. Price Increases from Online Privacy


    Ward, Michael R; Chen, Yu-Ching


    Consumers value keeping some information about them private from potential marketers. E-commerce dramatically increases the potential for marketers to accumulate otherwise private information about potential customers. Online marketers claim that this information enables them to better market their products. Policy makers are currently drafting rules to regulate the way in which these marketers can collect, store, and share this information. However, there is little evidence yet either of con...

  4. [Increasing interest in cold therapy]. (United States)

    Johansson, Bengt W


    Hypothermia was used early in the treatment of malignant tumors. New evidence shows that hypothermia protects normal tissues from the toxic effects of radiation and chemotherapeutic drugs. Hypothermia in oncological research is calculated to increase the therapeutic ratio by protecting normal tissue while retaining the antineoplastic effect. Animal results indicate that removal of the primary tumor using cryosurgery diminishes metastatic tumor growth more than does surgical excision.

  5. Experiencing discrimination increases risk taking. (United States)

    Jamieson, Jeremy P; Koslov, Katrina; Nock, Matthew K; Mendes, Wendy Berry


    Prior research has revealed racial disparities in health outcomes and health-compromising behaviors, such as smoking and drug abuse. It has been suggested that discrimination contributes to such disparities, but the mechanisms through which this might occur are not well understood. In the research reported here, we examined whether the experience of discrimination affects acute physiological stress responses and increases risk-taking behavior. Black and White participants each received rejecting feedback from partners who were either of their own race (in-group rejection) or of a different race (out-group rejection, which could be interpreted as discrimination). Physiological (cardiovascular and neuroendocrine) changes, cognition (memory and attentional bias), affect, and risk-taking behavior were assessed. Significant participant race × partner race interactions were observed. Cross-race rejection, compared with same-race rejection, was associated with lower levels of cortisol, increased cardiac output, decreased vascular resistance, greater anger, increased attentional bias, and more risk-taking behavior. These data suggest that perceived discrimination is associated with distinct profiles of physiological reactivity, affect, cognitive processing, and risk taking, implicating direct and indirect pathways to health disparities.

  6. Revising probability estimates: Why increasing likelihood means increasing impact. (United States)

    Maglio, Sam J; Polman, Evan


    Forecasted probabilities rarely stay the same for long. Instead, they are subject to constant revision-moving upward or downward, uncertain events become more or less likely. Yet little is known about how people interpret probability estimates beyond static snapshots, like a 30% chance of rain. Here, we consider the cognitive, affective, and behavioral consequences of revisions to probability forecasts. Stemming from a lay belief that revisions signal the emergence of a trend, we find in 10 studies (comprising uncertain events such as weather, climate change, sex, sports, and wine) that upward changes to event-probability (e.g., increasing from 20% to 30%) cause events to feel less remote than downward changes (e.g., decreasing from 40% to 30%), and subsequently change people's behavior regarding those events despite the revised event-probabilities being the same. Our research sheds light on how revising the probabilities for future events changes how people manage those uncertain events. (PsycINFO Database Record

  7. Increase Productivity Through Knowledge Management (United States)

    Gavrikova, N. A.; Dolgih, I. N.; Dyrina, E. N.


    Increase in competition level requires companies to improve the efficiency of work force use characterized by labor productivity. Professional knowledge of staff and its experience play the key role in it. The results of Extrusion Line operator’s working time analysis are performed in this article. The analysis revealed that the reasons of working time ineffective use connected with inadequate information exchange and knowledge management in the company. Authors suggest the way to solve this problem: the main sources of knowledge in engineering enterprise have been defined, the conditions of success and the stages of knowledge management control have been stated.

  8. Prostacyclin Increases Portal Venous Flow. (United States)


    response curve . We2 constructed a dose response curve by using increasing doses of PGI (0.005, 0.05, 0.5, and 5.0 ug/kg) given through the left atrial...atropine 0 40- +1 S20- X ( 0- * -20 -40 , 0.005 0.05 0.5 5.0 DOSE jig/kg Figure 2A (top). The log dose response curve of femoral artery pressure (FAP...Figure 2B (bottom). The log dose response curve of {. pulmonary artery pressure (PAP). Both figures show the maximum . deviation from baseline

  9. Public knowledge about AIDS increasing. (United States)

    Campbell, M J; Waters, W E


    In response to concern over the perceived limited effectiveness of Department of Health and Social Security (UK) advertising campaigns to inform the public of the basic facts of Acquired Immunodeficiency Syndrome (AIDS), a prospective questionnaire study was undertaken in Southampton, England to test the effectiveness of government education prior to a January, 1987 government television/leaflet advertising campaign. 300 questionnaires about AIDS were mailed in December of 1986 to a sample drawn from electoral rolls. The response rate was 61%. Most of the questions were drawn from material covered in the campaign. The results seemed to indicate a small overall increase in knowledge about AIDS. Some changes from a June survey were noted, e.g.: more people were aware that AIDS is a virus for which there is no cure and that it is not readily transmitted by sharing washing, eating or drinking utensils; more people believed that the statement that women are at greater risk for catching AIDS is false. Respondents were generally favorable to the government's continued use of television, even with explicit language, and to its use of the schools, for AIDS education. Many were not aware of the dangers to intravenous drug users or of the symptoms of AIDS. Other surveys have shown an increasing knowledge of AIDS dangers. It is possible that television coverage of the problem will continue to be necessary, in order that less literate populations be reached. Further AIDS health education in general is needed.

  10. Increasing entropy for colloidal stabilization (United States)

    Mo, Songping; Shao, Xuefeng; Chen, Ying; Cheng, Zhengdong


    Stability is of paramount importance in colloidal applications. Attraction between colloidal particles is believed to lead to particle aggregation and phase separation; hence, stability improvement can be achieved through either increasing repulsion or reducing attraction by modifying the fluid medium or by using additives. Two traditional mechanisms for colloidal stability are electrostatic stabilization and steric stabilization. However, stability improvement by mixing attractive and unstable particles has rarely been considered. Here, we emphasize the function of mixing entropy in colloidal stabilization. Dispersion stability improvement is demonstrated by mixing suspensions of attractive nanosized titania spheres and platelets. A three-dimensional phase diagram is proposed to illustrate the collaborative effects of particle mixing and particle attraction on colloidal stability. This discovery provides a novel method for enhancing colloidal stability and opens a novel opportunity for engineering applications.

  11. Increase in composite binder activity (United States)

    Fediuk, R.; Smoliakov, A.; Stoyushko, N.


    The binder of portland cement (51-59 wt.%), fly ash of thermal power stations (3644 wt.%), limestone crushing waste (4-9 wt.%) and dry hyper plasticizer (0.2 wt.%) has been created. It can be used in the building materials industry for production of high-strength concrete. The composite binder is obtained by co-milling of the components in vario-planetary mill to a specific surface area of 550-600 m2/kg. The technical result is the possibility of obtaining a composite binder with significant replacement of cement with industrial waste, cost-effective and superior to portland cement for construction and technical properties, increased activity. This allows producing concrete for walling with a compressive strength of 100 MPa, while using more than 50% of industrial waste.

  12. Moire interferometry with increased sensitivity (United States)

    Han, Bongtae; Post, Daniel

    The basic sensitivity of moire interferometry was increased beyond the previously conceived theoretical limit. This was accomplished by creating the virtual reference grating inside a refractive medium instead of air, thus shortening the wavelength of light. A very compact four-beam moire interferometer in a refractive medium was developed for microscopic viewing, which produced a basic sensitivity of 208 nm per fringe order, corresponding to moire with 4800 lines per mm. Its configuration made it inherently stable and relatively insensitive to environmental disturbances. An optical microscope was employed as the image recording system to obtain high spatial resolution. The method was demonstrated for deformation of a thick graphite/epoxy composite at the 0/90 deg ply interface.

  13. Propofol directly increases tau phosphorylation.

    Directory of Open Access Journals (Sweden)

    Robert A Whittington

    Full Text Available In Alzheimer's disease (AD and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology. Anesthetics have been previously shown to induce tau hyperphosphorylation through a mechanism involving hypothermia-induced inhibition of protein phosphatase 2A (PP2A activity. However, the effects of propofol, a common clinically used intravenous anesthetic, on tau phosphorylation under normothermic conditions are unknown. We investigated the effects of a general anesthetic dose of propofol on levels of phosphorylated tau in the mouse hippocampus and cortex under normothermic conditions. Thirty min following the administration of propofol 250 mg/kg i.p., significant increases in tau phosphorylation were observed at the AT8, CP13, and PHF-1 phosphoepitopes in the hippocampus, as well as at AT8, PHF-1, MC6, pS262, and pS422 epitopes in the cortex. However, we did not detect somatodendritic relocalization of tau. In both brain regions, tau hyperphosphorylation persisted at the AT8 epitope 2 h following propofol, although the sedative effects of the drug were no longer evident at this time point. By 6 h following propofol, levels of phosphorylated tau at AT8 returned to control levels. An initial decrease in the activity and expression of PP2A were observed, suggesting that PP2A inhibition is at least partly responsible for the hyperphosphorylation of tau at multiple sites following 30 min of propofol exposure. We also examined tau phosphorylation in SH-SY5Y cells transfected to overexpress human tau. A 1 h exposure to a clinically relevant concentration of propofol in vitro was also associated with tau hyperphosphorylation. These findings suggest that propofol increases tau phosphorylation both in vivo and in vitro under normothermic conditions, and further studies are warranted to determine the impact of this anesthetic on the acceleration of

  14. Scientific progress as increasing verisimilitude. (United States)

    Niiniluoto, Ilkka


    According to the foundationalist picture, shared by many rationalists and positivist empiricists, science makes cognitive progress by accumulating justified truths. Fallibilists, who point out that complete certainty cannot be achieved in empirical science, can still argue that even successions of false theories may progress toward the truth. This proposal was supported by Karl Popper with his notion of truthlikeness or verisimilitude. Popper's own technical definition failed, but the idea that scientific progress means increasing truthlikeness can be expressed by defining degrees of truthlikeness in terms of similarities between states of affairs. This paper defends the verisimilitude approach against Alexander Bird who argues that the "semantic" definition (in terms of truth or truthlikeness alone) is not sufficient to define progress, but the "epistemic" definition referring to justification and knowledge is more adequate. Here Bird ignores the crucial distinction between real progress and estimated progress, explicated by the difference between absolute (and usually unknown) degrees of truthlikeness and their evidence-relative expected values. Further, it is argued that Bird's idea of returning to the cumulative model of growth requires an implausible trick of transforming past false theories into true ones.

  15. Vocal attractiveness increases by averaging. (United States)

    Bruckert, Laetitia; Bestelmeyer, Patricia; Latinus, Marianne; Rouger, Julien; Charest, Ian; Rousselet, Guillaume A; Kawahara, Hideki; Belin, Pascal


    Vocal attractiveness has a profound influence on listeners-a bias known as the "what sounds beautiful is good" vocal attractiveness stereotype [1]-with tangible impact on a voice owner's success at mating, job applications, and/or elections. The prevailing view holds that attractive voices are those that signal desirable attributes in a potential mate [2-4]-e.g., lower pitch in male voices. However, this account does not explain our preferences in more general social contexts in which voices of both genders are evaluated. Here we show that averaging voices via auditory morphing [5] results in more attractive voices, irrespective of the speaker's or listener's gender. Moreover, we show that this phenomenon is largely explained by two independent by-products of averaging: a smoother voice texture (reduced aperiodicities) and a greater similarity in pitch and timbre with the average of all voices (reduced "distance to mean"). These results provide the first evidence for a phenomenon of vocal attractiveness increases by averaging, analogous to a well-established effect of facial averaging [6, 7]. They highlight prototype-based coding [8] as a central feature of voice perception, emphasizing the similarity in the mechanisms of face and voice perception.

  16. The increasing burden of depression

    Directory of Open Access Journals (Sweden)

    Lépine J-P


    Full Text Available Jean-Pierre Lépine1, Mike Briley21Hôpital Lariboisière Fernand Widal, Assistance Publique Hôpitaux de Paris Unité INSERM 705 CNRS UMR 8206, Université Paris Diderot, Paris, France; 2NeuroBiz Consulting and Communication, Castres, FranceAbstract: Recent epidemiological surveys conducted in general populations have found that the lifetime prevalence of depression is in the range of 10% to 15%. Mood disorders, as defined by the World Mental Health and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, have a 12-month prevalence which varies from 3% in Japan to over 9% in the US. A recent American survey found the prevalence of current depression to be 9% and the rate of current major depression to be 3.4%. All studies of depressive disorders have stressed the importance of the mortality and morbidity associated with depression. The mortality risk for suicide in depressed patients is more than 20-fold greater than in the general population. Recent studies have also shown the importance of depression as a risk factor for cardiovascular death. The risk of cardiac mortality after an initial myocardial infarction is greater in patients with depression and related to the severity of the depressive episode. Greater severity of depressive symptoms has been found to be associated with significantly higher risk of all-cause mortality including cardiovascular death and stroke. In addition to mortality, functional impairment and disability associated with depression have been consistently reported. Depression increases the risk of decreased workplace productivity and absenteeism resulting in lowered income or unemployment. Absenteeism and presenteeism (being physically present at work but functioning suboptimally have been estimated to result in a loss of $36.6 billion per year in the US. Worldwide projections by the World Health Organization for the year 2030 identify unipolar major depression as the leading cause of disease burden

  17. Alcohol causes a fatty pancreas. A rat model of ethanol-induced pancreatic steatosis. (United States)

    Wilson, J S; Colley, P W; Sosula, L; Pirola, R C; Chapman, B A; Somer, J B


    To develop an animal mode of alcoholic pancreatic steatosis, female Wistar rats were pair fed liquid diets, containing ethanol as 36% of calories or an isocaloric amount of carbohydrate for 3 weeks. Electron microscopic examination showed lipid vesicles localized principally at the bases of pancreatic acinar cells in the ethanol-fed rats. Ethanol feeding significantly increased pancreatic content of cholesteryl ester without changing levels of other lipids. Ethanol feeding enhanced labeled acetate, palmitate, oleate, and linoleate incorporation into cholesteryl ester. Therefore, increased esterification of cholesterol may, in part, explain the observed accumulation of cholesteryl ester.

  18. ProAlgaZyme and its subfractions increase plasma HDL cholesterol via upregulation of ApoA1, ABCA1, and SRB1, and inhibition of CETP in hypercholesterolemic hamsters

    Directory of Open Access Journals (Sweden)

    Geamanu A


    Full Text Available Andreea Geamanu, Nadia Saadat, Arvind Goja, Monika Wadehra, Xiangming Ji, Smiti V GuptaNutrition and Food Science, Wayne State University, Detroit, MI, USABackground: Plasma HDL cholesterol levels are inversely related to cardiovascular disease, which is the leading cause of death worldwide. This study investigated the effect of an algae infusion, ProAlgaZyme (PAZ, and its subfractions (P1, P2, P3, P4 on plasma HDL in a hamster model.Methods: Sixty male golden Syrian hamsters (8 weeks old were randomized into controls (W or PAZ (P, P1, P2, P3, and P4 (n = 10 per group. An infusion of either 5% (P1, P2, P3 or 20% (P, P4 concentration (v/v was administered via the drinking water for 4 weeks, while the hamsters were being fed a high-fat diet (30% of calories from fat. Serum lipids were assayed and liver samples subjected to reverse transcription polymerase chain reaction to determine the relative transcription levels of genes involved in HDL/reverse cholesterol transport metabolism, ie, ApoA1, ABCA1, CETP, and SRB1.Results: Non-HDL cholesterol was significantly reduced in the P (P < 0.05, P3 and P4 (P < 0.001 groups as compared with the W group, while HDL cholesterol showed a significant increase in the P, P3, and P4 groups (P < 0.001. Moreover, the total cholesterol/HDL ratio was significantly improved in the P, P1, and P2 (P < 0.05, and P3 and P4 (P < 0.001 groups. The shift in cholesterol towards the higher density fractions was validated by density gradient ultracentrifugation. Real-time quantitative polymerase chain reaction showed a significant increase in hepatic ApoA1 (P, P4 and ABCA1 (P3, P4 expression, consistent with an increase in HDL production, biogenesis, and maturation. A two-fold increase in SRB1 expression indicates that P4 further augments the reverse cholesterol transport mechanism. Reduction of CETP expression (P4 is consistent with a decrease in the transfer of cholesteryl ester to LDL, further increasing the amount of

  19. Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis

    NARCIS (Netherlands)

    de Sain-van der Velden, M; Kaysen, GA; Barrett, HA; Stellaard, F; Gadellaa, MM; Voorbij, HA; Reijngoud, DJ; Rabelink, TJ


    Increased very low density lipoprotein (VLDL) in nephrotic patients results from a decreased catabolism while increased low density lipoprotein (LDL) results from increased synthesis. Hyperlipidemias a hallmark of nephrotic syndrome that has been associated with increased risk for ischemic heart dis

  20. 14 CFR 381.13 - Price increases. (United States)


    ... REGULATIONS SPECIAL EVENT TOURS § 381.13 Price increases. (a) Should the tour operator increase a participant's tour price by more than 10 percent (aggregate of all increases to that participant), that... refund within 14 days after the cancellation. (b) The tour operator shall not increase the tour price...

  1. Increased rheumatoid factor and deep venous thrombosis

    DEFF Research Database (Denmark)

    Meyer-Olesen, Christine L; Nielsen, Sune F; Nordestgaard, Børge G


    BACKGROUND: The risk of deep venous thrombosis is increased in patients with rheumatoid arthritis. We tested the hypothesis that increased concentrations of rheumatoid factor are associated with increased risk of deep venous thrombosis in individuals without autoimmune rheumatic disease...... venous thrombosis. CONCLUSIONS: Increased rheumatoid factor in the general population was associated with up to 3-fold increased long-term risk and up to 9-fold increased 1-year risk of deep venous thrombosis....... was incident deep venous thrombosis. There were no losses to follow-up. RESULTS: During 368381 person-years, 670 individuals developed deep venous thrombosis. A rheumatoid factor concentration ≥ vs venous thrombosis, with multivariable adjusted hazard...

  2. 3 Ways to Increase Positive Emotions (United States)

    ... Healthy Breakfasts Shyness 3 Ways to Increase Positive Emotions KidsHealth > For Teens > 3 Ways to Increase Positive ... to give yourself a boost. Track Your Positive Emotions Name the positive emotions you're already familiar ...

  3. Having Rheumatoid Arthritis May Increase Heart Risk (United States)

    ... Having Rheumatoid Arthritis May Increase Heart Risk Treating inflammation linked to ... TUESDAY, Nov. 15, 2016 (HealthDay News) -- People with rheumatoid arthritis may have an increased risk for a heart ...

  4. Many Private Colleges Report Small Tuition Increases. (United States)

    Geraghty, Mary


    Many private colleges are reporting the lowest percentage tuition increases in a decade or more, four to five% at many institutions, but most increases still outpace inflation. A major reason for increasing tuition is to meet rising demand for student aid. Also, many institutional expenses are higher than for the average consumer, and facilities…

  5. Increasing ideological tolerance in social psychology. (United States)

    Inbar, Yoel; Lammers, Joris


    We argue that recognizing current ideological diversity in social psychology and promoting tolerance of minority views is just as important as increasing the number of non-liberal researchers. Increasing tolerance will allow individuals in the minority to express dissenting views, which will improve psychological science by reducing bias. We present four recommendations for increasing tolerance.

  6. Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease

    NARCIS (Netherlands)

    P.J. Barter; J.J.P. Kastelein


    Epidemiologic studies have shown that the concentration of high-density lipoprotein cholesterol (HDL-C) is a strong, independent, inverse predictor of coronary heart disease risk. This identifies HDL-C as a potential therapeutic target. Compared with low-density lipoprotein cholesterol (LDL-C)-lower

  7. Cholesteryl Ester Transfer Protein (CETP) genotype and cognitive function in persons aged 35 years or older

    NARCIS (Netherlands)

    Izaks, Gerbrand J.; van der Knaap, Aafke M.; Gansevoort, Ron T.; Navis, Gerjan; Slaets, Joris P. J.; Dullaart, Robin P. F.


    Common polymorphisms of the Cholestryl Ester Transfer Protein (CETP) gene may predict lower risk of cognitive decline. We investigated the association of cognitive function with CETP genotype in a population-based cohort of 4135 persons aged 35-82 years. Cognitive function was measured with the Ruff

  8. Cholesteryl ester transfer protein (cetp) inhibition in the treatment of cancer

    KAUST Repository

    Kaur, Mandeep


    In one embodiment, the invention provides methods of treatment which use therapeutically effective amounts of Choleste ryl Ester Transfer Protein (CETP) inhibitors to treat a variety of cancers. In certain embodiments, the inhibitor is a CETP-inhibiting small molecule, CETP-inhibiting antisense oligonucleotide, CETP-inhibiting siRNA or a CETP- inhibiting antibody. Related pharmaceutical compositions, kits, diagnostics and screens are also provided.

  9. Reduced leucocyte cholesteryl ester transfer protein expression in acute coronary syndromes

    NARCIS (Netherlands)

    Ye, D; Kraaijeveld, A O; Grauss, R W; Willems, S M; van Vark-van der Zee, L C; de Jager, S C A; Jauhiainen, M; Kuivenhoven, J A; Dallinga-Thie, G M; Atsma, D E; Hogendoorn, P C W; Biessen, E A L; Van Berkel, T J C; Jukema, J W; van Eck, M


    OBJECTIVE: Cholesterol ester transfer protein (CETP) plays an important role in HDL cholesterol metabolism. Leucocytes, including monocyte-derived macrophages in the arterial wall synthesize and secrete CETP, but its role in atherosclerosis is unclear. The aim of the current study was to investigate

  10. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth;


    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity....... Skeletal muscle specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist Prazosin to the drinking water of Sprague Dawley rats (n=33) while 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-week Prazosin treatment, which ensured......-body insulin sensitivity increased by ~24% and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]-Glucose disposal increased by ~30% concomitant with a ~20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake...

  11. Increased muscle glucose uptake during contractions

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Galbo, H; Richter, E A


    We reinvestigated the prevailing concept that muscle contractions only elicit increased muscle glucose uptake in the presence of a so-called "permissive" concentration of insulin (Berger et al., Biochem. J. 146: 231-238, 1975; Vranic and Berger, Diabetes 28: 147-163, 1979). Hindquarters from rats...... in severe ketoacidosis were perfused with a perfusate containing insulin antiserum. After 60 min perfusion, electrical stimulation increased glucose uptake of the contracting muscles fivefold. Also, subsequent contractions increased glucose uptake in hindquarters from nondiabetic rats perfused for 1.5 h......-methylglucose uptake increased during contractions and glucose uptake was negative at rest and zero during contractions. An increase in muscle transport and uptake of glucose during contractions does not require the presence of insulin. Furthermore, glucose transport in contracting muscle may only increase if glycogen...

  12. Taurine increases hippocampal neurogenesis in aging mice

    Directory of Open Access Journals (Sweden)

    Elias Gebara


    Full Text Available Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging.

  13. Are diseases increasing in the ocean? (United States)

    Lafferty, Kevin D.; Porter, James W.; Ford, Susan E.


    Many factors (climate warming, pollution, harvesting, introduced species) can contribute to disease outbreaks in marine life. Concomitant increases in each of these makes it difficult to attribute recent changes in disease occurrence or severity to any one factor. For example, the increase in disease of Caribbean coral is postulated to be a result of climate change and introduction of terrestrial pathogens. Indirect evidence exists that (a) warming increased disease in turtles; (b) protection, pollution, and terrestrial pathogens increased mammal disease; (c) aquaculture increased disease in mollusks; and (d) release from overfished predators increased sea urchin disease. In contrast, fishing and pollution may have reduced disease in fishes. In other taxa (e.g., sea grasses, crustaceans, sharks), there is little evidence that disease has changed over time. The diversity of patterns suggests there are many ways that environmental change can interact with disease in the ocean.

  14. Passive thermal performance increase in cisterns


    Najmeh Najafi, Arash Alipour, Seyed Mohamad Ali Najafi


    Cisterns are ancient building having two main tasks. First task is storing water in raining seasons for using in dry seasons and the second task is decreasing water temperature, which happens because of the air flow above water surface and evaporating water. It can be stated that by increasing fluid flow above the surface, evaporating increase so increasing in heat transfer happens and decreasing of water temperature is the result. This paper has investigated fluid flow around and inside cist...

  15. Familial skin cancer syndromes: Increased melanoma risk. (United States)

    Ransohoff, Katherine J; Jaju, Prajakta D; Jaju, Prajaka D; Tang, Jean Y; Carbone, Michele; Leachman, Sancy; Sarin, Kavita Y


    Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings.

  16. Does Twitter Increase Perceived Police Legitimacy?

    NARCIS (Netherlands)

    Grimmelikhuijsen, Stephan G|info:eu-repo/dai/nl/313875405; Meijer, Albert J|info:eu-repo/dai/nl/172436729


    Social media use has become increasingly popular among police forces. The literature suggests that social media use can increase perceived police legitimacy by enabling transparency and participation. Employing data from a large and representative survey of Dutch citizens (N = 4,492), this article t

  17. Exergames: Increasing Physical Activity through Effective Instruction (United States)

    Rudella, Jennifer L.; Butz, Jennifer V.


    Due to the growing obesity epidemic in the United States, educators must consider new ways to increase physical activity in an effort to address obesity. There are a variety of ways educators can increase physical activity in the classroom, and exergames--video games that require physical movement in order to play--are a modern-day approach to…

  18. Cyberbullying: An Increasing Challenge for Schools (United States)

    von Marees, Nandoli; Petermann, Franz


    The use of information and communication technology (ICT) has not only brought advantages to mankind. One downside is the emergence and increase of cyberbullying in schools. Affecting students of all ages, teachers, parents, and other educators, this special form of bullying is an increasing challenge for schools. This article offers an overview…

  19. Wilson's disease; increased aluminum in liver. (United States)

    Yasui, M; Yoshimasu, F; Yase, Y; Uebayashi, Y


    Interaction of trace metal metabolism was studied in a patient with Wilson's dease. Atomic absorption analysis showed markedly increased urinary excretion of copper and aluminum and an increased aluminum content was found in the biopsied liver by neutron activation analysis. These findings suggest a complicated pathogenetic mechanism involving other metals besides copper in the Wilson's disease.

  20. Are increases in cigarette taxation regressive? (United States)

    Borren, P; Sutton, M


    Using the latest published data from Tobacco Advisory Council surveys, this paper re-evaluates the question of whether or not increases in cigarette taxation are regressive in the United Kingdom. The extended data set shows no evidence of increasing price-elasticity by social class as found in a major previous study. To the contrary, there appears to be no clear pattern in the price responsiveness of smoking behaviour across different social classes. Increases in cigarette taxation, while reducing smoking levels in all groups, fall most heavily on men and women in the lowest social class. Men and women in social class five can expect to pay eight and eleven times more of a tax increase respectively, than their social class one counterparts. Taken as a proportion of relative incomes, the regressive nature of increases in cigarette taxation is even more pronounced.

  1. Increasing trends of herpes zoster in Australia.

    Directory of Open Access Journals (Sweden)

    Raina MacIntyre

    Full Text Available Increasing trends in incidence of herpes zoster (HZ have been reported in Australia and internationally. This may reflect the impact of childhood VZV vaccination programs introduced universally in Australia in late 2005. The objective of this study was to evaluate changes in incidence of HZ and PHN in Australia over time, and associated healthcare resource utilisation.Australian data on general practice (GP encounters for HZ, specific antiviral prescribing data from the pharmaceutical benefits scheme, emergency department presentations from the states of NSW and Victoria and national hospitalisation data for HZ were analysed for time trends using regression models. Two time periods (2000-2006 and 2006-2013 were compared which correspond broadly with the pre- and post- universal VZV vaccination period.All data sources showed increasing rates of HZ with age and over time. The GP database showed a significant annual increase in encounters for HZ of 2.5 per 100,000 between 1998 and 2013, and the rates of prescriptions for HZ increased by 4.2% per year between 2002 and 2012. In the 60+ population HZ incidence was estimated to increase from 11.9 to 15.4 per 1,000 persons using GP data or from 12.8 to 14.2 per 1,000 persons using prescription data (p<0.05, between the two periods. Hospitalisation data did not show the same increasing trend over time, except for the age group ≥80 years. Most emergency visits for HZ were not admitted, and showed significant increases over time.The burden of HZ in Australia is substantial, and continues to increase over time. This increase is seen both pre- and post-universal VZV vaccination in 2005, and is most prominent in the older population. The substantial burden of HZ, along with ageing of the Australian population and the importance of healthy ageing, warrants consideration of HZ vaccination for the elderly.

  2. Increasing mental health literacy via narrative advertising. (United States)

    Chang, Chingching


    This research explored the effectiveness of narrative advertising and argument advertising in increasing mental illness (depression) literacy. Results showed that narrative advertising was more effective than argument advertising at engaging participants in experiential immersion, resulting in greater sympathy toward those suffering from depression. In addition, narrative advertising better involved participants in issue elaboration and increased willingness to seek professional help. Finally, in comparison with argument advertising, narrative advertisements were rated higher in providing vivid information, resulting in an increase in participants' perceived efficacy in recognizing friends or family suffering from depression.

  3. Tobacco use increases susceptibility to bacterial infection

    Directory of Open Access Journals (Sweden)

    Demuth Donald R


    Full Text Available Abstract Active smokers and those exposed to secondhand smoke are at increased risk of bacterial infection. Tobacco smoke exposure increases susceptibility to respiratory tract infections, including tuberculosis, pneumonia and Legionnaires disease; bacterial vaginosis and sexually transmitted diseases, such as chlamydia and gonorrhoea; Helicobacter pylori infection; periodontitis; meningitis; otitis media; and post-surgical and nosocomial infections. Tobacco smoke compromises the anti-bacterial function of leukocytes, including neutrophils, monocytes, T cells and B cells, providing a mechanistic explanation for increased infection risk. Further epidemiological, clinical and mechanistic research into this important area is warranted.

  4. Increasing bedbug, Cimex lectularius, infestations in Kuwait. (United States)

    El-Azazy, Osama M E; Al-Behbehani, Bahja; Abdou, Nadra-Elwgoud M I


    Bedbug, Cimex lectularius, human infestations were reported in the State of Kuwait in the last 2 years. Eleven separate infestations from different localities were received at the Veterinary Laboratories indicating that bedbug is widespread in the State of Kuwait. There was circumstantial evidence to suggest the transfer of bugs with recent immigrants or used furniture. The spread of infestation can be attributed to the increase in migrant labor and their mobility inside the country. The increase in reported cases appears also consistent with a worldwide increase in bedbug infestations.

  5. The increased importance of sector switching

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Hansen, Jesper Rosenberg


    Sector switching is an important phenomenon that casts light on public–private differences. Yet our knowledge about its prevalence and trends is limited. We study sector switching using unique Danish register-based employer–employee data covering more than 25 years. We find that sector switching...... constitutes 18.5% of all job-to-job mobility, and the trend is increasing both from public to private and from private to public. Sector switching is also generally increasing for middle managers, but for administrative professionals only the flows from private to public increase and for top managers only...

  6. The world-wide increase in tuberculosis: how demographic changes, HIV infection and increasing numbers in poverty are increasing tuberculosis. (United States)

    Davies, Peter D O


    After more than a century of decline, in the mid 1980s tuberculosis began to increase in some developed countries. Health care workers were then forced to look to the developing world, where they found tuberculosis to be out of control, in many countries. It is now appreciated that tuberculosis is not only increasing globally but is likely to do so beyond the next decade for three principal reasons. First, demographically as the expected population increase will be greatest in areas of the world where tuberculosis is most prevalent, particularly middle Africa and South Asia. Secondly, the increase of HIV, which renders the host uniquely susceptible to tuberculosis, is occurring in the same areas of the world and is already causing an increase in tuberculosis case rates of up to tenfold. Thirdly, as more and more people are forced to live in poverty, where poor nutrition and crowded conditions lead to the spread of tuberculosis, the disease risk will be compounded. Sound medical management, particularly the use of the five components of directly observed therapy, will relieve the situation. But until world conditions of poverty and HIV spread are addressed, it is unlikely that tuberculosis can be controlled.

  7. The ways of SOFC systems efficiency increasing

    Energy Technology Data Exchange (ETDEWEB)

    Demin, A.K.; Timofeyeva, N.


    The efficiency of solid oxide fuel cells (SOFCs) is described. This paper considers methods to lift the fuel utilization and/or the average cell voltage with the goal of increasing the cell efficiency by improved cell designs.

  8. Autism overflows: increasing prevalence and proliferating theories. (United States)

    Waterhouse, Lynn


    This selective review examines the lack of an explanation for the sharply increasing prevalence of autism, and the lack of any synthesis of the proliferating theories of autism. The most controversial and most widely disseminated notion for increasing prevalence is the measles-mumps-rubella/thimerosal vaccine theory. Less controversial causes that have been proposed include changes in autism diagnostic criteria, increasing services for autism, and growing awareness of the disorder. Regardless of its causes, the increasing prevalence of autism has put pressure on the field of autism research to generate productive and predictive theories of autism. However, the heterogeneity of brain deficits, impaired behaviors, and genetic variants in autism have challenged researchers and theorists, and despite 45 years of research, no standard causal synthesis has emerged. Research going forward should assume that autism is an aggregation of myriad independent disorders of impaired sociality, social cognition, communication, and motor and cognitive skills.

  9. Increasing incidence of diabetes after gestational diabetes

    DEFF Research Database (Denmark)

    Lauenborg, Jeannet; Hansen, Torben; Jensen, Dorte Møller;


    To study the incidence of diabetes among women with previous diet-treated gestational diabetes mellitus (GDM) in the light of the general increasing incidence of overweight and diabetes and to identify risk factors for the development of diabetes....

  10. Hyperestrogenemia and increased blood mercury level

    Institute of Scientific and Technical Information of China (English)

    Viroj Wiwanitkit


    Hyperestrogenemia is an important reproductive hormone abnormality. This condition is not common in male patients. In this report, the author presents a case study on hyperestrogenemia with increased blood mercury level. The metalloestrogen phenomenon is discussed.

  11. Increase in the Array Television Camera Sensitivity (United States)

    Shakhrukhanov, O. S.

    A simple adder circuit for successive television frames that enables to considerably increase the sensitivity of such radiation detectors is suggested by the example of array television camera QN902K.

  12. Big increase in Spanish reseach funding

    CERN Multimedia

    Bosch, X


    The Spanish government plans to increase spending on civilian science research and development by between 8 and 10 per cent. The exact figure is unclear since it has been included in the budget along with military research projects (1 page).

  13. Increased aldosterone: mechanism of hypertension in obesity. (United States)

    Flynn, Colleen


    The prevalence of both obesity and hypertension are increasing worldwide. Hypertension is a common consequence of obesity. Increased central adiposity is associated with increased aldosterone levels and blood pressure in human beings. A number of small studies have shown an association between obesity-mediated hypertension and mechanisms directly linked to increased levels of aldosterone. These studies have shown a trend toward relatively greater blood pressure reduction using aldosterone-receptor blockers compared with other classes of antihypertensive agents. Other than treatment for weight loss, treatment of hypertension with specific antihypertensive medications that block or reduce aldosterone action are appropriate in obese patients. Further research is needed to understand the exact role of the adipocyte in obesity-mediated hypertension.

  14. Low Vitamin D: What Increases the Risk? (United States)

    ... Food Service Resources Additional Resources About FAQ Contact Low Vitamin D: What Increases The Risk? Our bodies ... use sunscreen daily are more likely to be low in vitamin D. ( 1 ) But don’t ditch ...

  15. Ethanologenic bacteria with increased resistance to furfural

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Elliot Norman; Jarboe, Laura R.; Yomano, Lorraine P.; York, Sean W.; Shanmugam, Keelnatham; Ingram, Lonnie O' Neal


    The invention relates to bacterium that have increased resistance to furfural and methods of preparation. The invention also relates to methods of producing ethanol using the bacterium and corresponding kits.

  16. Increasing incidence of diabetes after gestational diabetes

    DEFF Research Database (Denmark)

    Lauenborg, Jeannet; Hansen, Torben; Jensen, Dorte Møller


    To study the incidence of diabetes among women with previous diet-treated gestational diabetes mellitus (GDM) in the light of the general increasing incidence of overweight and diabetes and to identify risk factors for the development of diabetes.......To study the incidence of diabetes among women with previous diet-treated gestational diabetes mellitus (GDM) in the light of the general increasing incidence of overweight and diabetes and to identify risk factors for the development of diabetes....


    Institute of Scientific and Technical Information of China (English)

    HeWenjiong; ZhangYi


    The dual random models about the life insurance and social pension insurance have received considerable attention in the recent articles on actuarial theory and applications. This paper discusses a general kind of increasing annuity based on its force of interest accumulationfunction as a general random process. The dual random model of the present value of the benefits of the increasing annuity has been set, and their moments have been calculated under certainconditions.

  18. Expanding your practice and increasing its profitability. (United States)

    Hunter, Craig


    Part One of this article identifies specific operational aspects that each practice should consider to enhance its future position including increased work efficiencies and financial opportunities, capitalizing on technological resources. Part Two discusses provider expansion, expansion of procedural services, and implementation of successful marketing initiatives. By addressing these topics, the practice will strengthen its internal morale and teamwork while increasing existing revenue streams. It will also reduce operational expenses and consider new revenue sources that fit the goals and objectives of the partners.

  19. The Effect of Increasing Mass upon Locomotion (United States)

    DeWitt, John; Hagan, Donald


    The purpose of this investigation was to determine if increasing body mass while maintaining bodyweight would affect ground reaction forces and joint kinetics during walking and running. It was hypothesized that performing gait with increased mass while maintaining body weight would result in greater ground reaction forces, and would affect the net joint torques and work at the ankle, knee and hip when compared to gait with normal mass and bodyweight. Vertical ground reaction force was measured for ten subjects (5M/5F) during walking (1.34 m/s) and running (3.13 m/s) on a treadmill. Subjects completed one minute of locomotion at normal mass and bodyweight and at four added mass (AM) conditions (10%, 20%, 30% and 40% of body mass) in random order. Three-dimensional joint position data were collected via videography. Walking and running were analyzed separately. The addition of mass resulted in several effects. Peak impact forces and loading rates increased during walking, but decreased during running. Peak propulsive forces decreased during walking and did not change during running. Stride time increased and hip extensor angular impulse and positive work increased as mass was added for both styles of locomotion. Work increased at a greater rate during running than walking. The adaptations to additional mass that occur during walking are different than during running. Increasing mass during exercise in microgravity may be beneficial to increasing ground reaction forces during walking and strengthening hip musculature during both walking and running. Future study in true microgravity is required to determine if the adaptations found would be similar in a weightless environment.

  20. Chromium increases pancreatic metallothionein in the rat. (United States)

    Solis-Heredia, M J; Quintanilla-Vega, B; Sierra-Santoyo, A; Hernández, J M; Brambila, E; Cebrián, M E; Albores, A


    The ability of chromium (Cr) salts to increase metallothionein (MT) levels in rat liver, kidney and pancreas, and its relationship with the presence of toxic effects are reported here. Rats were injected subcutaneously with 0, 10, 20, 30, 40, or 50 mg K2Cr2O7/kg and sacrificed 24 h later. Total Cr accumulation followed a dose-dependent pattern, levels in kidney being higher than those in liver or pancreas, suggesting different tissue bioavailabilities and accumulation patterns. Cr(IV) administration resulted in a tissue-specific MT induction: pancreas and liver showed five- and 3.5-fold MT increases, respectively; no increase was observed in the kidney. A positive correlation was observed between zinc and MT concentrations in liver, and between total Cr and MT concentrations in pancreas. Serum alpha-amylase activity showed a dose-dependent increase starting from 20 mg/kg, whereas serum glucose levels increased at doses higher than 30 mg/kg. Serum aspartate aminotransferase and alanine aminotransferase activities were increased in a dose-dependent manner, from 20 and 30 mg/kg, respectively. Our results showed that treatment with Cr(VI) can induce MT synthesis in pancreas and suggests a subsequent binding of Cr to MT. Also, pancreas is a target organ for Cr toxicity, and the usefulness of alpha-amylase activity as a sensitive biomarker of Cr toxicity in human exposed populations merits further study.

  1. Wind increases leaf water use efficiency. (United States)

    Schymanski, Stanislaus J; Or, Dani


    A widespread perception is that, with increasing wind speed, transpiration from plant leaves increases. However, evidence suggests that increasing wind speed enhances carbon dioxide (CO2 ) uptake while reducing transpiration because of more efficient convective cooling (under high solar radiation loads). We provide theoretical and experimental evidence that leaf water use efficiency (WUE, carbon uptake per water transpired) commonly increases with increasing wind speed, thus improving plants' ability to conserve water during photosynthesis. Our leaf-scale analysis suggests that the observed global decrease in near-surface wind speeds could have reduced WUE at a magnitude similar to the increase in WUE attributed to global rise in atmospheric CO2 concentrations. However, there is indication that the effect of long-term trends in wind speed on leaf gas exchange may be compensated for by the concurrent reduction in mean leaf sizes. These unintuitive feedbacks between wind, leaf size and water use efficiency call for re-evaluation of the role of wind in plant water relations and potential re-interpretation of temporal and geographic trends in leaf sizes.

  2. Randomness in Sequence Evolution Increases over Time.

    Directory of Open Access Journals (Sweden)

    Guangyu Wang

    Full Text Available The second law of thermodynamics states that entropy, as a measure of randomness in a system, increases over time. Although studies have investigated biological sequence randomness from different aspects, it remains unknown whether sequence randomness changes over time and whether this change consists with the second law of thermodynamics. To capture the dynamics of randomness in molecular sequence evolution, here we detect sequence randomness based on a collection of eight statistical random tests and investigate the randomness variation of coding sequences with an application to Escherichia coli. Given that core/essential genes are more ancient than specific/non-essential genes, our results clearly show that core/essential genes are more random than specific/non-essential genes and accordingly indicate that sequence randomness indeed increases over time, consistent well with the second law of thermodynamics. We further find that an increase in sequence randomness leads to increasing randomness of GC content and longer sequence length. Taken together, our study presents an important finding, for the first time, that sequence randomness increases over time, which may provide profound insights for unveiling the underlying mechanisms of molecular sequence evolution.

  3. Exploring Increased Productivity Through Employee Engagement (United States)

    Richards, Wayne K., Jr.

    Disengaged employees cost U.S. companies billions of dollars annually in lowered productivity, a cost which has been compounded by the difficult economic situations in the country. The potential for increasing productivity through increased employee engagement was examined in this study. Using personal engagement theory and the theory of planned behavior, the purpose of this phenomenological study was to explore how the experiences of salaried aerospace employees affected productivity and the financial performance of an organization. Interviews were conducted with a purposive sample of 20 aerospace employees whose responses were codified and analyzed to identify themes. The analysis indicated that (a) the lived experiences of employees influenced employee engagement, (b) employee engagement affects organizational commitment and performance, and (c) trust and respect and leadership are essential components to keep employees engaged. Eighty percent of the participants indicated that as employee engagement increases so too does organizational performance. The implications for positive social change include new insights for leaders seeking to increase productivity and financial performance, and to support employee engagement for maintaining sustainability, retaining talent, increasing profits, and improving the economy.

  4. Passive thermal performance increase in cisterns

    Directory of Open Access Journals (Sweden)

    Najmeh Najafi, Arash Alipour, Seyed Mohamad Ali Najafi


    Full Text Available Cisterns are ancient building having two main tasks. First task is storing water in raining seasons for using in dry seasons and the second task is decreasing water temperature, which happens because of the air flow above water surface and evaporating water. It can be stated that by increasing fluid flow above the surface, evaporating increase so increasing in heat transfer happens and decreasing of water temperature is the result. This paper has investigated fluid flow around and inside cisterns with FLUENT software results. Increasing in air flow demand to the cistern is the primary purpose of this study, by changing main parameters of cistern geometry like increasing or decreasing of doom hale diameter, inlet and outlet of wind catcher, elevation of wind catcher and also wind speed. This study introduces the best geometry for cisterns according to maximum air flow demand and minimum volume. Considering that, there is a direct relation between heat transfer and airflow rate in cisterns, so in this study, the influence of mentioned parameters are investigated to reach optimum design for the best performance of cisterns.

  5. Birch Stands Growth Increase in Western Siberia (United States)

    Kharuk, Viacheslav I.; Kuzmichev, Valeriy V.; Im, Sergey T.; Ranson, Kenneth J.


    Birch (Betula pendula Roth) growth within the Western Siberia forest-steppe was analyzed based on long-term (1897-2006) inventory data (height, diameter at breast height [dbh], and stand volume). Analysis of biometry parameters showed increased growth at the beginning of twenty-first century compared to similar stands (stands age = 40-60 years) at the end of nineteenth century. Mean height, dbh, and stem volume increased from 14 to 20 m, from 16 to 22 cm, and from approx. 63 to approx. 220 cu m/ha, respectively. Significant correlations were found between the stands mean height, dbh, and volume on the one hand, and vegetation period length (r(sub s) = 0.71 to 0.74), atmospheric CO2 concentration (r(sub s) = 0.71 to 0.76), and drought index (Standardized Precipitation-Evapotranspiration Index, r(sub s) = -0.33 to -0.51) on the other hand. The results obtained have revealed apparent climate-induced impacts (e.g. increase of vegetation period length and birch habitat drying due to drought increase) on the stands growth. Along with this, a high correlation of birch biometric parameters and [CO2] in ambient air indicated an effect of CO2 fertilization. Meanwhile, further drought increase may switch birch stand growth into decline and greater mortality as has already been observed within the Trans-Baikal forest-steppe ecotone.

  6. Nutrient enrichment increases mortality of mangroves.

    Directory of Open Access Journals (Sweden)

    Catherine E Lovelock

    Full Text Available Nutrient enrichment of the coastal zone places intense pressure on marine communities. Previous studies have shown that growth of intertidal mangrove forests is accelerated with enhanced nutrient availability. However, nutrient enrichment favours growth of shoots relative to roots, thus enhancing growth rates but increasing vulnerability to environmental stresses that adversely affect plant water relations. Two such stresses are high salinity and low humidity, both of which require greater investment in roots to meet the demands for water by the shoots. Here we present data from a global network of sites that documents enhanced mortality of mangroves with experimental nutrient enrichment at sites where high sediment salinity was coincident with low rainfall and low humidity. Thus the benefits of increased mangrove growth in response to coastal eutrophication is offset by the costs of decreased resilience due to mortality during drought, with mortality increasing with soil water salinity along climatic gradients.

  7. Are rates of pediatric bipolar disorder increasing?

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Vradi, Eleni; Andersen, Per Kragh


    Studies from the USA suggest that rates of pediatric bipolar disorder have increased since the mid-90s, but no study outside the USA has been published on the rates of pediatric bipolar disorder. Further, it is unclear whether an increase in rates reflects a true increase in the illness or more...... diagnostic attention. Using nationwide registers of all inpatients and outpatients contacts to all psychiatric hospitals in Denmark, we investigated (1) gender-specific rates of incident pediatric mania/bipolar disorder during a period from 1995 to 2012, (2) whether age and other characteristics...... for pediatric mania/bipolar disorder changed during the calendar period (1995 to 2003 versus 2004 to 2012), and (3) whether the diagnosis is more often made at first psychiatric contact in recent time compared to earlier according to gender. Totally, 346 patients got a main diagnosis of a manic episode (F30...

  8. Increased health care utilisation in international adoptees

    DEFF Research Database (Denmark)

    Graff, Heidi Jeannet; Siersma, Volkert Dirk; Kragstrup, Jakob;


    after adoption. Our study aimed to theassess health-care utilisation of international adoptees inprimary and secondary care for somatic and psychiatricdiagnoses in a late post-adoption period. Is there an increaseduse of the health-care system in this period, evenwhen increased morbidity in the group...... of allservices in primary care, while in secondary care only fewareas showed an increased long-term morbidity. Conclusion: International adoptees use medical servicesin primary care at a higher rate than non-adoptees someyears after adoption. Excess use of services in secondarycare is also present, but only......Introduction: Several studies have documented thatinternational adoptees have an increased occurrence ofhealth problems and contacts to the health-care systemafter arriving to their new country of residence. This maybe explained by pre-adoption adversities, especially for theperiod immediately...

  9. Increased transvascular lipoprotein transport in diabetes

    DEFF Research Database (Denmark)

    Jensen, Jan Skov; Feldt-Rasmussen, Bo; Borch-Johnsen, Knut;


    CONTEXT: Diabetes is associated with a highly increased risk of atherosclerosis, especially if hypertension or albuminuria is present. OBJECTIVE: We hypothesized that the increased transvascular lipoprotein transport in diabetes may be further accelerated if hypertension or albuminuria is present......, possibly explaining increased intimal lipoprotein accumulation and thus atherosclerosis. DESIGN: The study was cross-sectional and was performed in 1999-2002. SETTING: The study took place in the referral center. PATIENTS: The patients included 60 with diabetes mellitus (27 with type 1 diabetes and 33...... with type 2 diabetes) and 42 healthy controls. All were randomly recruited. MAIN OUTCOME MEASURE: We used an in vivo method for measurement of transvascular transport of low-density lipoprotein (LDL). Autologous 131I-LDL was reinjected iv, and the 1-h fractional escape rate was taken as an index...

  10. Nutrient Enrichment Increases Mortality of Mangroves (United States)

    Lovelock, Catherine E.; Ball, Marilyn C.; Martin, Katherine C.; C. Feller, Ilka


    Nutrient enrichment of the coastal zone places intense pressure on marine communities. Previous studies have shown that growth of intertidal mangrove forests is accelerated with enhanced nutrient availability. However, nutrient enrichment favours growth of shoots relative to roots, thus enhancing growth rates but increasing vulnerability to environmental stresses that adversely affect plant water relations. Two such stresses are high salinity and low humidity, both of which require greater investment in roots to meet the demands for water by the shoots. Here we present data from a global network of sites that documents enhanced mortality of mangroves with experimental nutrient enrichment at sites where high sediment salinity was coincident with low rainfall and low humidity. Thus the benefits of increased mangrove growth in response to coastal eutrophication is offset by the costs of decreased resilience due to mortality during drought, with mortality increasing with soil water salinity along climatic gradients. PMID:19440554

  11. Increasing the weight of minimum spanning trees

    Energy Technology Data Exchange (ETDEWEB)

    Frederickson, G.N.; Solis-Oba, R. [Purdue Univ., West Lafayette, IN (United States)


    Given an undirected connected graph G and a cost function for increasing edge weights, the problem of determining the maximum increase in the weight of the minimum spanning trees of G subject to a budget constraint is investigated. Two versions of the problem are considered. In the first, each edge has a cost function that is linear in the weight increase. An algorithm is presented that solves this problem in strongly polynomial time. In the second version, the edge weights are fixed but an edge can be removed from G at a unit cost. This version is shown to be NP-hard. An {Omega}(1/ log k)-approximation algorithm is presented for it, where k is the number of edges to be removed.

  12. Barriers to increasing market-oriented activity

    DEFF Research Database (Denmark)

    Bisp, Søren

    product development. Despite the increasing evidence of a positive relationship between above average business performance and a high level of market-oriented activity, normative recommendations on how to increase the level of market-oriented activity is sparse. The scientific contribution of the present...... research is to expand the understanding of what factors inhibit the increase of market-oriented activity and how these factors may interact. Identifying and describing the barriers is considered the first and necessary step in attempting to reach a higher level of market-oriented activity......Introduction: The Danish food processing industry faces a situation in which intensified competition in its primary markets and product categories forces several companies to rethink their relative focus in terms of marketing rather than production, or, in other words, in terms of value adding...

  13. Role of biofertilizers in increasing tea productivity

    Institute of Scientific and Technical Information of China (English)

    P Nepolean; R Jayanthi; R Vidhya Pallavi; A Balamurugan; T Kuberan; T Beulah; R Premkumar


    Objective: To increase the tea productivity using biofertilizers like VAM fungi, phosphobacteria, Azosprillium. Methods: Nitrogen fixing Azospirillum, phosphate solubilising bacteria and VAM fungi were isolated from tea soils of southern India and region specific potential strains were selected based on laboratory, greenhouse, as well as field experiments. A technology for their mass multiplication has been developed. Results: Biofertilizers were showed higher yield at the rate of 5g/seedling and VAM fungi with 15 g of formulation/bush. Conclusions: Multifunctional biofertilizers were used to reduce the chemical fertilizers, diseases and to increase soil fertility in tea.

  14. Increasing dominance of IT in ICT convergence

    DEFF Research Database (Denmark)

    Henten, Anders; Tadayoni, Reza

    The aim of the paper is to examine the increasing dominance of IT companies in the converging ICT industry and, on the basis of this development, to contribute to extending the theoretical understanding of market and industry convergence in the ICT area.......The aim of the paper is to examine the increasing dominance of IT companies in the converging ICT industry and, on the basis of this development, to contribute to extending the theoretical understanding of market and industry convergence in the ICT area....

  15. Has risk associated with smoking increased?

    DEFF Research Database (Denmark)

    Prescott, E; Osler, M; Andersen, P K


    population representative of the general Danish population and whether any such changes relate to changes in smoking behaviour. METHODS: Pooled data from three prospective population studies conducted in Copenhagen with detailed information on smoking habits. A total of 31,194 subjects, 17,669 males and 13...... smokers with never-smokers) did not change in the study period. In females, ratios increased from 1964-1978 to 1979-1994 by a factor of 1.3 (95% confidence interval 1.0-1.8). CONCLUSIONS: In agreement with the observed changes in smoking habits, excess mortality in male smokers did not increase whereas...

  16. Increasing loads on mine centrifugal blowers

    Energy Technology Data Exchange (ETDEWEB)

    Kovalevskaya, V.I.; Pak, V.V. (Donetskii Politekhnicheskii Institut (USSR))


    Increasing output of blowers for ventilation of deep coal mines by enlarging their dimensions and increasing revolution rate is uneconomic and technically complicated. Optimization of aerodynamic characteristics of the blowers is most economic. Effects of blower blade geometry (shape and cross-section) on blower output, air pressure and efficiency are analyzed. On the basis of Euler's equations a method is discussed for determining optimum aerodynamic parameters of the modified blade geometry that guarantees the most economic blower operation. 7 refs.

  17. Using synthetic biology to increase nitrogenase activity


    Li, Xin-Xin; Liu, Qi; Liu, Xiao-Meng; Shi, Hao-Wen; Chen, San-feng


    Background Nitrogen fixation has been established in protokaryotic model Escherichia coli by transferring a minimal nif gene cluster composed of 9 genes (nifB, nifH, nifD, nifK, nifE, nifN, nifX, hesA and nifV) from Paenibacillus sp. WLY78. However, the nitrogenase activity in the recombinant E. coli 78-7 is only 10 % of that observed in wild-type Paenibacillus. Thus, it is necessary to increase nitrogenase activity through synthetic biology. Results In order to increase nitrogenase activity ...

  18. Coal exporters win significant price increases

    Energy Technology Data Exchange (ETDEWEB)



    Coal exports won a 3 dollars/t or almost 8% rise in hard coking coal prices to lift the benchmark Goonyella brand to 42.75 dollars/t. This was followed by major price increases for semi-hard coking coal with the prices of some grades increased by 8 dollars/t or by more than 23%. The new prices will come into effect for the year beginning April, 2001 and acre then first price rises in two years. The article reviews the major Asia countries with their coal supply information. 1 tab., 4 photos.


    Directory of Open Access Journals (Sweden)

    Diego Pacheco


    Full Text Available The main objective of this article is to point a set of practical strategies that can be adopted to increase the capacity of constraints resources on production systems, when the constraint is inside the factory and not is in the market. To serve this purpose will be presented strategies based on best practices of the Theory of Constraints, Lean Manufacturing and Total Productive Maintenance. This article also presents the mains tools for the deployment of these methodologies. The survey results have provided an objective set of practical strategy that can be used to increase the capacity and productivity of production systems according to the needs of each manufacturing system.

  20. Fresh inflation with increasing cosmological parameter

    CERN Document Server

    Bellini, M


    I study a fresh inflationary model with an increasing F-cosmological parameter. The model provides sufficiently e-folds to solve the flatness/horizon problem and the density fluctuations agree with experimental values. The temperature increases during fresh inflation and reach its maximum value when inflation ends. I find that entropy perturbations always remain below $10^{-4}$ during fresh inflation and become negligible when fresh inflation ends. Hence, the adiabatic fluctuations dominate the primordial spectrum at the end of fresh inflation.

  1. Increased health care utilisation in international adoptees

    DEFF Research Database (Denmark)

    Graff, Heidi Jeannet; Siersma, Volkert Dirk; Kragstrup, Jakob;


    after adoption. Our study aimed to theassess health-care utilisation of international adoptees inprimary and secondary care for somatic and psychiatricdiagnoses in a late post-adoption period. Is there an increaseduse of the health-care system in this period, evenwhen increased morbidity in the group...... comprised internationallyadopted children (n = 6,820), adopted between 1994 and2005, and all non-adopted children (n = 492,374) who couldbe matched with the adopted children on sex, age, municipalityand family constellation at the time of adoption. Results: International adoption increased the use...

  2. Robotic Bipedal Running: Increasing disturbance rejection

    NARCIS (Netherlands)

    Karssen, J.G.D.


    The goal of the research presented in this thesis is to increase the understanding of the human running gait. The understanding of the human running gait is essential for the development of devices, such as prostheses and orthoses, that enable disabled people to run or that enable able people to inc

  3. Increasing Incidence of Juvenile Thyrotoxicosis in Denmark

    DEFF Research Database (Denmark)

    Kjær, R. H.; Andersen, M. S.; Hansen, D.


    . Additional data were collected on children diagnosed with GD in 2008-2012. Results: In total, 237 patients with juvenile thyrotoxicosis (JT) were identified. The overall IR in 1998-2012 was 1.58/100,000 person-years and has increased significantly from 0.79/100,000 person-years in 1982-1988 (p

  4. Increasing Reading Engagement in African American Boys (United States)

    Husband, Terry


    Much has been written concerning the challenges many teachers face in engaging African American males in reading practices. While much of this extant scholarship focuses on African American males at the pre-adolescent stage of development and beyond, little has been written regarding increasing reading engagement in African American boys in P-5…

  5. Liver Abscess: Increasing Occurrence in Premature Newborns

    Directory of Open Access Journals (Sweden)



    Full Text Available Neonatal liver abscess is a very rare condition associated with high morbidity and mortality rates. There seems to be an increasing trend of this rare condition amongst the newborns admitted to neonatal intensive care units. We report a case of liver abscess in a premature newborn and briefly review the literature and discuss its management.

  6. Liver Abscess: Increasing Occurrence in Premature Newborns (United States)

    Bosnalı, Oktav; Moralıoğlu, Serdar; Pektaş, Osman


    Neonatal liver abscess is a very rare condition associated with high morbidity and mortality rates. There seems to be an increasing trend of this rare condition amongst the newborns admitted to neonatal intensive care units. We report a case of liver abscess in a premature newborn and briefly review the literature and discuss its management. PMID:26023443

  7. Liver Abscess: Increasing Occurrence in Premature Newborns

    Directory of Open Access Journals (Sweden)

    Oktav Bosnalı


    Full Text Available Neonatal liver abscess is a very rare condition associated with high morbidity and mortality rates. There seems to be an increasing trend of this rare condition amongst the newborns admitted to neonatal intensive care units. We report a case of liver abscess in a premature newborn and briefly review the literature and discuss its management.

  8. Increased carrying capacity with perennial forage kochia (United States)

    Carrying capacity can be increased on grass-dominated rangeland pastures by including perennial forage kochia (Kochia prostrata) as one of the plant components. The objectives of the study reported here were to compare the differences of traditional winter pastures versus pastures with forage kochi...

  9. Collaboration among sectors to increase pulse consumption. (United States)

    Curran, Julianne; McLachlan, Milla; Black, Richard; Widders, Irv; Manary, Mark


    The United Nations declaration of 2016 as the International Year of Pulses (IYP) provided an unprecedented opportunity to showcase pulses on the global stage for their contribution to affordable nutrition, health, and sustainability. Despite the IYP's successes in stakeholder engagement, continuing to foster and strengthen partnerships and collaborations is necessary to meet the IYP goals of increased pulse production and consumption for human benefit. Shifting consumer behavior to increase pulse consumption emerged during IYP meetings as a shared priority for all stakeholders. Focusing on this shared priority provides an opportunity to strengthen collaboration among all stakeholder groups for research, education, marketing, and ingredient/food production. Although the IYP officially closed at the end of 2016, the pulse community has an opportunity to continue building successful collaborations. The future research agenda can foster increased pulse production and consumption to address global nutrition, health, and sustainability challenges, provided that it is developed with multisectorial perspectives and cross-disciplinary collaborations. But, most importantly, the research agenda for pulses must be centered more deliberately on the end consumer and how to drive shifts in behavior toward increased pulse consumption, as this is the common shared priority around which all stakeholders can rally.

  10. Increasing security in inter-chip communication (United States)

    Edwards, Nathan J; Hamlet, Jason; Bauer, Todd; Helinski, Ryan


    An apparatus for increasing security in inter-chip communication includes a sending control module, a communication bus, and a receiving control module. The communication bus is coupled between the sending control module and the receiving control module. The sending control module operates to send data on the communication bus, disable the communication bus when threats are detected, or both.

  11. Environmental lead exposure increases micronuclei in children

    DEFF Research Database (Denmark)

    Kapka, Lucyna; Baumgartner, Adolf; Siwińska, Ewa


    and control group (standard MN test: 2.96 +/- 2.36 versus 1.16 +/- 1.28; FISH technique: 3.57 +/- 3.02 versus 1.43 +/- 1.69, respectively). The frequencies of both centromere-positive (C+MN) and centromere-negative (C-MN) micronuclei were significantly increased in exposed children; however, the contribution...

  12. Increased Gonorrhea Cases - Utah, 2009-2014. (United States)

    Watson, Joanna; Carlile, Jerry; Dunn, Angela; Evans, Megan; Fratto, Erin; Hartsell, Joel; Meinor, Lynn; Mietchen, Matthew; Nakashima, Allyn


    Gonorrhea (caused by infection with Neisseria gonorrhoeae) is the second most commonly reported notifiable disease in the United States (1). Left untreated, gonorrhea is associated with serious long-term adverse health effects, including pelvic inflammatory disease, ectopic pregnancy, and infertility. Infection also facilitates transmission of human immunodeficiency virus (2,3). Effective gonorrhea control relies upon early detection and effective antimicrobial treatment. To assess gonorrhea rate trends in Utah, the Utah Department of Health (UDOH) analyzed Utah National Electronic Disease Surveillance System (UT-NEDSS) data for the state during 2009-2014. After declining during 2009-2011, the statewide gonorrhea rate increased fivefold to 49 cases per 100,000 population in 2014. During 2009-2014, the proportion of cases among women increased from 21% to 39% (decreasing among males from 79% to 61%). Among male patients, the proportion who identified as men who have sex with men (MSM) decreased from 67% to 42%. These demographic changes suggest that increased heterosexual transmission of gonorrhea in Utah might be occurring. Health departments need to work with providers to ensure populations at high risk are being screened and properly treated for gonorrhea. Clinicians need to be aware of increases in the risk for infection among women and non-MSM males when making screening and testing decisions and educate their patients regarding gonorrhea transmission and prevention practices.

  13. Voluntary attention increases perceived spatial frequency. (United States)

    Abrams, Jared; Barbot, Antoine; Carrasco, Marisa


    Voluntary covert attention selects relevant sensory information for prioritized processing. The behavioral and neural consequences of such selection have been extensively documented, but its phenomenology has received little empirical investigation. Involuntary attention increases perceived spatial frequency (Gobell & Carrasco, 2005), but involuntary attention can differ from voluntary attention in its effects on performance in tasks mediated by spatial resolution (Yeshurun, Montagna, & Carrasco, 2008). Therefore, we ask whether voluntary attention affects the subjective appearance of spatial frequency--a fundamental dimension of visual perception underlying spatial resolution. We used a demanding rapid serial visual presentation task to direct voluntary attention and measured perceived spatial frequency at the attended and unattended locations. Attention increased the perceived spatial frequency of suprathreshold stimuli and also improved performance on a concurrent orientation discrimination task. In the control experiment, we ruled out response bias as an alternative account by using a lengthened interstimulus interval, which allows observers to disengage attention from the cued location. In contrast to the main experiment, the observers showed neither increased perceived spatial frequency nor improved orientation discrimination at the attended location. Thus, this study establishes that voluntary attention increases perceived spatial frequency. This phenomenological consequence links behavioral and neurophysiological studies on the effects of attention.

  14. Price of Vitamin B5 Increases Rapidly

    Institute of Scientific and Technical Information of China (English)


    @@ The export price of vitamin B5 in China has increased constantly in 2007. According to the analysis made by experts, the demand of vitamin B5 has not grown greatly. The main reason for the price rise is the change of the supply mode.

  15. Sex Equity: Increasing Girls' Use of Computers. (United States)

    Lockheed, Marlaine E.; Frakt, Steven B.


    Indicates that although computer science has been free of male domination, the stereotype of computers as male machines is emerging with increasing growth in microcomputer use by children. Factors that account for this development and some strategies teachers can adopt to equalize computer use by boys and girls are presented. (MBR)

  16. Motivating Intervention Strategies to Increase Homework Completion (United States)

    Amerine, Melissa; Pender, Lisa; Schuler, Kristin


    The purpose of this action research project was to increase homework completion through the use of motivating strategies. There were approximately 75 students, 100 parents, and three teacher researchers involved in this study. The three intervention strategies used were 15 minutes of class time, extrinsic rewards, and assignment notebook checks.…

  17. Increased cerebral water content in hemodialysis patients.

    Directory of Open Access Journals (Sweden)

    Kathrin Reetz

    Full Text Available Little information is available on the impact of hemodialysis on cerebral water homeostasis and its distribution in chronic kidney disease. We used a neuropsychological test battery, structural magnetic resonance imaging (MRI and a novel technique for quantitative measurement of localized water content using 3T MRI to investigate ten hemodialysis patients (HD on a dialysis-free day and after hemodialysis (2.4±2.2 hours, and a matched healthy control group with the same time interval. Neuropsychological testing revealed mainly attentional and executive cognitive dysfunction in HD. Voxel-based-morphometry showed only marginal alterations in the right inferior medial temporal lobe white matter in HD compared to controls. Marked increases in global brain water content were found in the white matter, specifically in parietal areas, in HD patients compared to controls. Although the global water content in the gray matter did not differ between the two groups, regional increases of brain water content in particular in parieto-temporal gray matter areas were observed in HD patients. No relevant brain hydration changes were revealed before and after hemodialysis. Whereas longer duration of dialysis vintage was associated with increased water content in parieto-temporal-occipital regions, lower intradialytic weight changes were negatively correlated with brain water content in these areas in HD patients. Worse cognitive performance on an attention task correlated with increased hydration in frontal white matter. In conclusion, long-term HD is associated with altered brain tissue water homeostasis mainly in parietal white matter regions, whereas the attentional domain in the cognitive dysfunction profile in HD could be linked to increased frontal white matter water content.

  18. A mechanistic study to increase understanding of titanium dioxide nanoparticles-increased plasma glucose in mice. (United States)

    Hu, Hailong; Li, Li; Guo, Qian; Jin, Sanli; Zhou, Ying; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning


    Titanium dioxide nanoparticle (TiO2 NP) is an authorized food additive. Previous studies determined oral administration of TiO2 NPs increases plasma glucose in mice via inducing insulin resistance. An increase in reactive oxygen species (ROS) has been considered the possible mechanism of increasing plasma glucose. However, persistently high plasma glucose is also a mechanism of increasing ROS. This study aims to explore whether TiO2 NPs increase plasma glucose via ROS. We found after oral administration of TiO2 NPs, an increase in ROS preceded an increase in plasma glucose. Subsequently, mice were treated with two antioxidants (resveratrol and vitamin E) at the same time as oral administration of TiO2 NPs. Results showed resveratrol and vitamin E reduced TiO2 NPs-increased ROS. An increase in plasma glucose was also inhibited. Further research showed resveratrol and vitamin E inhibited the secretion of TNF-α and IL-6, and the phosphorylation of JNK and p38 MAPK, resulting in improved insulin resistance. These results suggest TiO2 NPs increased ROS levels, and then ROS activated inflammatory cytokines and phosphokinases, and thus induced insulin resistance, resulting in an increase in plasma glucose. Resveratrol and vitamin E can reduce TiO2 NPs-increased ROS and thereby inhibit an increase in plasma glucose in mice.

  19. Shopper marketing nutrition interventions: Social norms on grocery carts increase produce spending without increasing shopper budgets

    Directory of Open Access Journals (Sweden)

    Collin R. Payne


    Conclusions: Descriptive and provincial social norm messages (i.e., on grocery cart placards may be an overlooked tool to increase produce demand without decreasing store profitability and increasing shopper budgets.

  20. Increased taxon sampling greatly reduces phylogenetic error. (United States)

    Zwickl, Derrick J; Hillis, David M


    Several authors have argued recently that extensive taxon sampling has a positive and important effect on the accuracy of phylogenetic estimates. However, other authors have argued that there is little benefit of extensive taxon sampling, and so phylogenetic problems can or should be reduced to a few exemplar taxa as a means of reducing the computational complexity of the phylogenetic analysis. In this paper we examined five aspects of study design that may have led to these different perspectives. First, we considered the measurement of phylogenetic error across a wide range of taxon sample sizes, and conclude that the expected error based on randomly selecting trees (which varies by taxon sample size) must be considered in evaluating error in studies of the effects of taxon sampling. Second, we addressed the scope of the phylogenetic problems defined by different samples of taxa, and argue that phylogenetic scope needs to be considered in evaluating the importance of taxon-sampling strategies. Third, we examined the claim that fast and simple tree searches are as effective as more thorough searches at finding near-optimal trees that minimize error. We show that a more complete search of tree space reduces phylogenetic error, especially as the taxon sample size increases. Fourth, we examined the effects of simple versus complex simulation models on taxonomic sampling studies. Although benefits of taxon sampling are apparent for all models, data generated under more complex models of evolution produce higher overall levels of error and show greater positive effects of increased taxon sampling. Fifth, we asked if different phylogenetic optimality criteria show different effects of taxon sampling. Although we found strong differences in effectiveness of different optimality criteria as a function of taxon sample size, increased taxon sampling improved the results from all the common optimality criteria. Nonetheless, the method that showed the lowest overall

  1. Increasing muscle extensibility: a matter of increasing length or modifying sensation?

    DEFF Research Database (Denmark)

    Weppler, Cynthia Holzman; Magnusson, S Peter


    Various theories have been proposed to explain increases in muscle extensibility observed after intermittent stretching. Most of these theories advocate a mechanical increase in length of the stretched muscle. More recently, a sensory theory has been proposed suggesting instead that increases in ...

  2. Do fat supplements increase physical performance? (United States)

    Macaluso, Filippo; Barone, Rosario; Catanese, Patrizia; Carini, Francesco; Rizzuto, Luigi; Farina, Felicia; Di Felice, Valentina


    Fish oil and conjugated linoleic acid (CLA) belong to a popular class of food supplements known as "fat supplements", which are claimed to reduce muscle glycogen breakdown, reduce body mass, as well as reduce muscle damage and inflammatory responses. Sport athletes consume fish oil and CLA mainly to increase lean body mass and reduce body fat. Recent evidence indicates that this kind of supplementation may have other side-effects and a new role has been identified in steroidogenensis. Preliminary findings demonstrate that fish oil and CLA may induce a physiological increase in testosterone synthesis. The aim of this review is to describe the effects of fish oil and CLA on physical performance (endurance and resistance exercise), and highlight the new results on the effects on testosterone biosynthesis. In view of these new data, we can hypothesize that fat supplements may improve the anabolic effect of exercise.

  3. Playing violent video games increases intergroup bias. (United States)

    Greitemeyer, Tobias


    Previous research has shown how, why, and for whom violent video game play is related to aggression and aggression-related variables. In contrast, less is known about whether some individuals are more likely than others to be the target of increased aggression after violent video game play. The present research examined the idea that the effects of violent video game play are stronger when the target is a member of an outgroup rather than an ingroup. In fact, a correlational study revealed that violent video game exposure was positively related to ethnocentrism. This relation remained significant when controlling for trait aggression. Providing causal evidence, an experimental study showed that playing a violent video game increased aggressive behavior, and that this effect was more pronounced when the target was an outgroup rather than an ingroup member. Possible mediating mechanisms are discussed.

  4. Increase of Organization in Complex Systems

    CERN Document Server

    Georgiev, Georgi Yordanov; Gombos, Erin; Vinod, Amrit; Hoonjan, Gajinder


    Measures of complexity and entropy have not converged to a single quantitative description of levels of organization of complex systems. The need for such a measure is increasingly necessary in all disciplines studying complex systems. To address this problem, starting from the most fundamental principle in Physics, here a new measure for quantity of organization and rate of self-organization in complex systems based on the principle of least (stationary) action is applied to a model system - the central processing unit (CPU) of computers. The quantity of organization for several generations of CPUs shows a double exponential rate of change of organization with time. The exact functional dependence has a fine, S-shaped structure, revealing some of the mechanisms of self-organization. The principle of least action helps to explain the mechanism of increase of organization through quantity accumulation and constraint and curvature minimization with an attractor, the least average sum of actions of all elements ...

  5. Do Fat Supplements Increase Physical Performance?

    Directory of Open Access Journals (Sweden)

    Valentina Di Felice


    Full Text Available Fish oil and conjugated linoleic acid (CLA belong to a popular class of food supplements known as “fat supplements”, which are claimed to reduce muscle glycogen breakdown, reduce body mass, as well as reduce muscle damage and inflammatory responses. Sport athletes consume fish oil and CLA mainly to increase lean body mass and reduce body fat. Recent evidence indicates that this kind of supplementation may have other side-effects and a new role has been identified in steroidogenensis. Preliminary findings demonstrate that fish oil and CLA may induce a physiological increase in testosterone synthesis. The aim of this review is to describe the effects of fish oil and CLA on physical performance (endurance and resistance exercise, and highlight the new results on the effects on testosterone biosynthesis. In view of these new data, we can hypothesize that fat supplements may improve the anabolic effect of exercise.

  6. Leptospirosis: a globally increasing zoonotic disease.

    LENUS (Irish Health Repository)

    Rock, Clare


    A 27-year-old previously healthy man was admitted to the intensive care unit with severe jaundice, dyspnoea with haemoptysis, anaemia, thrombocytopenia and acute renal injury. He had no recent history of foreign travel but had been building a shed in his back garden in Cork, Ireland, for the preceding week. The patient\\'s history, clinical observations, haematological and radiological results were all consistent with icteric leptospirosis or Weil\\'s disease. This was confirmed on serological testing. He completed 7 days intravenous ceftriaxone and made a complete recovery. While endemic in tropical climates, leptospirosis incidence is increasing in temperate climates. Recent cases seen in temperate climates can be severe, particularly with pulmonary manifestations. The report of this case serves to increase awareness of this re-emerging potentially fatal infectious disease.

  7. Increasing the efficiency of solar thermal panels (United States)

    Dobrnjac, M.; Latinović, T.; Dobrnjac, S.; Živković, P.


    The popularity of solar heating systems is increasing for several reasons. These systems are reliable, adaptable and pollution-free, because the renewable solar energy is used. There are many variants of solar systems in the market mainly constructed with copper pipes and absorbers with different quality of absorption surface. Taking into account the advantages and disadvantages of existing solutions, in order to increase efficiency and improve the design of solar panel, the innovative solution has been done. This new solar panel presents connection of an attractive design and the use of constructive appropriate materials with special geometric shapes. Hydraulic and thermotechnical tests that have been performed on this panel showed high hydraulic and structural stability. Further development of the solar panel will be done in the future in order to improve some noticed disadvantages.

  8. Interference comb-spectroscopy with increasing sensitivity (United States)

    Pulkin, Sergey; Borisov, Evgenii; Balabas, Michail; Uvarova, Svetlana; Shevtzov, Vladimir; Kalinichev, Alexei; Shoev, Vladislav; Venediktov, Dmitrii; Venediktov, Vladimir


    The paper considers the use of holographic interferometer for hologram recording of the wide spectrum from the comb - generator of the femtosecond laser was applied for illuminating of Michelson interferometer with atomic vapor. The behavior of spectral interference fringes on the exit slit of spectrograph reflects the behavior of nonlinear refractive index. The method of holographic interferometry with increasing sensitivity using phase modulator was applied for digital hologram processing.

  9. CNOOC Reports Significant Increase in 2006 Profits

    Institute of Scientific and Technical Information of China (English)


    @@ China National Offshore Oil Corporation (CNOOC), the country's No.3 oil producer,recently announced pretax profits jumped 24 percent to 48.1 billion yuan (US$6.2 billion) in 2006. The offshore oil giant reported 60.1 percent increase in pretax profits, totaling 38.8 billion yuan (US$5 billion) in 2005. Analysts said the dropped oil prices in the second half of last year had greatly affected the company's profit growth.

  10. Increasing the Confidence in Student's $t$ Interval


    Goutis, Constantinos; Casella, George


    The usual confidence interval, based on Student's $t$ distribution, has conditional confidence that is larger than the nominal confidence level. Although this fact is known, along with the fact that increased conditional confidence can be used to improve a confidence assertion, the confidence assertion of Student's $t$ interval has never been critically examined. We do so here, and construct a confidence estimator that allows uniformly higher confidence in the interval and is closer (than $1 ...

  11. A short proof of increased parabolic regularity

    Directory of Open Access Journals (Sweden)

    Stephen Pankavich


    Full Text Available We present a short proof of the increased regularity obtained by solutions to uniformly parabolic partial differential equations. Though this setting is fairly introductory, our new method of proof, which uses a priori estimates and an inductive method, can be extended to prove analogous results for problems with time-dependent coefficients, advection-diffusion or reaction diffusion equations, and nonlinear PDEs even when other tools, such as semigroup methods or the use of explicit fundamental solutions, are unavailable.

  12. Aridity under conditions of increased CO2 (United States)

    Greve, Peter; Roderick, Micheal L.; Seneviratne, Sonia I.


    A string of recent of studies led to the wide-held assumption that aridity will increase under conditions of increasing atmospheric CO2 concentrations and associated global warming. Such results generally build upon analyses of changes in the 'aridity index' (the ratio of potential evaporation to precipitation) and can be described as a direct thermodynamic effect on atmospheric water demand due to increasing temperatures. However, there is widespread evidence that contradicts the 'warmer is more arid' interpretation, leading to the 'global aridity paradox' (Roderick et al. 2015, WRR). Here we provide a comprehensive assessment of modeled changes in a broad set of dryness metrics (primarily based on a range of measures of water availability) over a large range of realistic atmospheric CO2 concentrations. We use an ensemble of simulations from of state-of-the-art climate models to analyse both equilibrium climate experiments and transient historical simulations and future projections. Our results show that dryness is, under conditions of increasing atmospheric CO2 concentrations and related global warming, generally decreasing at global scales. At regional scales we do, however, identify areas that undergo changes towards drier conditions, located primarily in subtropical climate regions and the Amazon Basin. Nonetheless, the majority of regions, especially in tropical and mid- to northern high latitudes areas, display wetting conditions in a warming world. Our results contradict previous findings and highlight the need to comprehensively assess all aspects of changes in hydroclimatological conditions at the land surface. Roderick, M. L., P. Greve, and G. D. Farquhar (2015), On the assessment of aridity with changes in atmospheric CO2, Water Resour. Res., 51, 5450-5463

  13. The RMB Exchange Rate Keeps Increasing

    Institute of Scientific and Technical Information of China (English)


    @@ In July 2005, the People's Bank of China officially announced that it would adopt a manageable floating exchange rate, adjusted according to a basket of currencies based on market supply and demand. On that day, the exchange rate of the RMB to the U.S. Dollar increased by 21 percent, and since then the RMB exchange rate has gradually turned to a more flexible exchange rate convention, rather than focusing on the Dollar only.

  14. Increasing demands on today's blood donors


    McClelland, W. M.


    Recently in Northern Ireland there has been a rapid increase in demand for a variety of blood components. To meet this need a large proportion of routine blood donations must be processed at the Transfusion Centre. In addition, several blood components are collected direct from donors by apheresis techniques. Apheresis is currently restricted to the collection of components from highly selected donors, but in future this method is likely to be employed for collection of some routine component...

  15. Symbiosis increases coral tolerance to ocean acidification

    Directory of Open Access Journals (Sweden)

    S. Ohki


    Full Text Available Increasing the acidity of ocean waters will directly threaten calcifying marine organisms such as reef-building scleractinian corals, and the myriad of species that rely on corals for protection and sustenance. Ocean pH has already decreased by around 0.1 pH units since the beginning of the industrial revolution, and is expected to decrease by another 0.2–0.4 pH units by 2100. This study mimicked the pre-industrial, present, and near-future levels of pCO2 using a precise control system (±5% pCO2, to assess the impact of ocean acidification on the calcification of recently-settled primary polyps of Acropora digitifera, both with and without symbionts, and adult fragments with symbionts. The increase in pCO2 of 100 μatm between the pre-industrial period and the present had more effect on the calcification rate of adult A. digitifera than the anticipated future increases of several hundreds of micro-atmospheres of pCO2. The primary polyps with symbionts showed higher calcification rates than primary polyps without symbionts, suggesting that (i primary polyps housing symbionts are more tolerant to near-future ocean acidification than organisms without symbionts, and (ii corals acquiring symbionts from the environment (i.e. broadcasting species will be more vulnerable to ocean acidification than corals that maternally acquire symbionts.

  16. Happiness increases distraction by auditory deviant stimuli. (United States)

    Pacheco-Unguetti, Antonia Pilar; Parmentier, Fabrice B R


    Rare and unexpected changes (deviants) in an otherwise repeated stream of task-irrelevant auditory distractors (standards) capture attention and impair behavioural performance in an ongoing visual task. Recent evidence indicates that this effect is increased by sadness in a task involving neutral stimuli. We tested the hypothesis that such effect may not be limited to negative emotions but reflect a general depletion of attentional resources by examining whether a positive emotion (happiness) would increase deviance distraction too. Prior to performing an auditory-visual oddball task, happiness or a neutral mood was induced in participants by means of the exposure to music and the recollection of an autobiographical event. Results from the oddball task showed significantly larger deviance distraction following the induction of happiness. Interestingly, the small amount of distraction typically observed on the standard trial following a deviant trial (post-deviance distraction) was not increased by happiness. We speculate that happiness might interfere with the disengagement of attention from the deviant sound back towards the target stimulus (through the depletion of cognitive resources and/or mind wandering) but help subsequent cognitive control to recover from distraction.

  17. Increasing incidence of coeliac disease in Sweden. (United States)

    Ascher, H; Krantz, I; Kristiansson, B


    Changes in the incidence of coelic disease was studied among children born in Göteborg, Sweden, between 1970 and 1988. A total of 188 patients with coeliac disease were found. Of these, 83% were less than 2 years old at the time of their first duodenal biopsy and 74% of them have so far been verified according to the criteria of the European Society for Gastroenterology and Nutrition (ESPGAN). The cumulative incidence at 2 years of age/1000 liveborn infants increased significantly from 0.31 in the first birth cohort to 2.93 in the last. This increase could only partly be explained by improvements in detection. Weight for age at diagnosis was generally considerably below the reference value, but was slightly less affected towards the end of the period. The increase in incidence of coeliac disease is the first reported since the middle 1970s and makes the disease one of the most common chronic diseases among Swedish children. PMID:2039251

  18. Clusters - Tourism Activity Increase Competitiveness Support

    Directory of Open Access Journals (Sweden)

    Carmen IORDACHE


    Full Text Available Tourism represents one of those areas with the greatest potential of global expansion. Tourism development strategy in terms of maximizing its positive effects on regional economic increase and implicitly on the national one starts from the premise that in global economy value is created in regions which are defined as particular geographical entities, separated by geographical reasons and not as political-administrative structures, and economic increase is centrally cumulated and valued according to the economic policy and the national legal system.Regional economic system approach based on “cluster” concept is explained by the fact that the regional activities portfolio is based on an inter and intra-industry networking grouped by cluster, in which is created the value that increases as the activity results are leading to the final consumers.This type of communication aims to highlight the tourism role as a factor in regional development, the clustering process significance in obtaining some competitiveness advantages, clusters development in tourism beginnings, and also the identification methodology used to select one touristic area to create the cluster.


    Directory of Open Access Journals (Sweden)

    G. O. Magomedov


    Full Text Available Summary. Technology for producing milk candies on molasses with increased shelf-life, molded by "extrusion" with a vacuum syringe of continuous action used in the meat industry, into metallized film like "flow-pack" is considered. Rheological characteristics of candy mass: strength, toughness, organoleptic, physical and chemical quality are determined. While increasing the temperature of milk mass the colour, texture, mass fraction of reducing substances and solids change. It was found out that molasses based milk mass is easily molded at a moisture content of 10-11 % and temperature of 60 ºС. The advantages of the new method of forming products are: manufactured products have individual package, which increases the shelf life and improves the quality of products, extend the range of use, the technological equipment has a high productivity, it is compact and reliable. According to the consumer qualities the product surpasses all known analogs. Possibility of using a single-piece product while gathering dinners and breakfasts in public catering, establishments and transport. The technological process is simplified. Energy value of products on molasses in comparison with the control samples on sugar is calculated. It is 51 kcal less than in the control sample on sugar. Thus, the technology of functional milk candies with reduced sugar content is developed. The products will be useful for anyone who leads a healthy lifestyle.

  20. Polyploidization increases meiotic recombination frequency in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Rehmsmeier Marc


    Full Text Available Abstract Background Polyploidization is the multiplication of the whole chromosome complement and has occurred frequently in vascular plants. Maintenance of stable polyploid state over generations requires special mechanisms to control pairing and distribution of more than two homologous chromosomes during meiosis. Since a minimal number of crossover events is essential for correct chromosome segregation, we investigated whether polyploidy has an influence on the frequency of meiotic recombination. Results Using two genetically linked transgenes providing seed-specific fluorescence, we compared a high number of progeny from diploid and tetraploid Arabidopsis plants. We show that rates of meiotic recombination in reciprocal crosses of genetically identical diploid and autotetraploid Arabidopsis plants were significantly higher in tetraploids compared to diploids. Although male and female gametogenesis differ substantially in meiotic recombination frequency, both rates were equally increased in tetraploids. To investigate whether multivalent formation in autotetraploids was responsible for the increased recombination rates, we also performed corresponding experiments with allotetraploid plants showing strict bivalent pairing. We found similarly increased rates in auto- and allotetraploids, suggesting that the ploidy effect is independent of chromosome pairing configurations. Conclusions The evolutionary success of polyploid plants in nature and under domestication has been attributed to buffering of mutations and sub- and neo-functionalization of duplicated genes. Should the data described here be representative for polyploid plants, enhanced meiotic recombination, and the resulting rapid creation of genetic diversity, could have also contributed to their prevalence.

  1. Increased Science Instrumentation Funding Strengthens Mars Program (United States)

    Graham, Lee D.; Graff, T. G.


    As the strategic knowledge gaps mature for the exploration of Mars, Mars sample return (MSR), and Phobos/Deimos missions, one approach that becomes more probable involves smaller science instrumentation and integrated science suites. Recent technological advances provide the foundation for a significant evolution of instrumentation; however, the funding support is currently too small to fully utilize these advances. We propose that an increase in funding for instrumentation development occur in the near-term so that these foundational technologies can be applied. These instruments would directly address the significant knowledge gaps for humans to Mars orbit, humans to the Martian surface, and humans to Phobos/ Deimos. They would also address the topics covered by the Decadal Survey and the Mars scientific goals, objectives, investigations and priorities as stated by the MEPAG. We argue that an increase of science instrumentation funding would be of great benefit to the Mars program as well as the potential for human exploration of the Mars system. If the total non-Earth-related planetary science instrumentation budget were increased 100% it would not add an appreciable amount to the overall NASA budget and would provide the real potential for future breakthroughs. If such an approach were implemented in the near-term, NASA would benefit greatly in terms of science knowledge of the Mars, Phobos/Deimos system, exploration risk mitigation, technology development, and public interest.

  2. Global warming without global mean precipitation increase? (United States)

    Salzmann, Marc


    Global climate models simulate a robust increase of global mean precipitation of about 1.5 to 2% per kelvin surface warming in response to greenhouse gas (GHG) forcing. Here, it is shown that the sensitivity to aerosol cooling is robust as well, albeit roughly twice as large. This larger sensitivity is consistent with energy budget arguments. At the same time, it is still considerably lower than the 6.5 to 7% K(-1) decrease of the water vapor concentration with cooling from anthropogenic aerosol because the water vapor radiative feedback lowers the hydrological sensitivity to anthropogenic forcings. When GHG and aerosol forcings are combined, the climate models with a realistic 20th century warming indicate that the global mean precipitation increase due to GHG warming has, until recently, been completely masked by aerosol drying. This explains the apparent lack of sensitivity of the global mean precipitation to the net global warming recently found in observations. As the importance of GHG warming increases in the future, a clear signal will emerge.

  3. Increasing Incidence of Canine Leptospirosis in Switzerland

    Directory of Open Access Journals (Sweden)

    Andrea Major


    Full Text Available A marked increase in canine leptospirosis was observed in Switzerland over 10 years with a peak incidence of 28.1 diagnosed cases/100,000 dogs/year in the most affected canton. With 95% affected dogs living at altitudes <800 m, the disease presented a seasonal pattern associated with temperature (r2 0.73 and rainfall (r2 0.39, >90% cases being diagnosed between May and October. The increasing yearly incidence however was only weakly correlated with climatic data including number of summer (r2 0.25 or rainy days (r2 0.38. Serovars Australis and Bratislava showed the highest seropositivity rates with 70.5% and 69.1%, respectively. Main clinical manifestations included renal (99.6%, pulmonary (76.7%, hepatic (26.0%, and hemorrhagic syndromes (18.2%, leading to a high mortality rate (43.3%. Similar to the human disease, liver involvement had the strongest association with negative outcome (OR 16.3. Based on these data, canine leptospirosis presents similar features and severity as the human infection for which it therefore can be considered a model. Its re-emergence in a temperate country with very high incidence rates in canines should thus be viewed as a warning and emphasize the need for increased awareness in other species.

  4. Increasing river floods: fiction or reality? (United States)

    Blöschl, Günter; Gaál, Ladislav; Hall, Julia; Kiss, Andrea; Komma, Jürgen; Nester, Thomas; Parajka, Juraj; Perdigão, Rui A P; Plavcová, Lenka; Rogger, Magdalena; Salinas, José Luis; Viglione, Alberto


    There has been a surprisingly large number of major floods in the last years around the world, which suggests that floods may have increased and will continue to increase in the next decades. However, the realism of such changes is still hotly discussed in the literature. This overview article examines whether floods have changed in the past and explores the driving processes of such changes in the atmosphere, the catchments and the river system based on examples from Europe. Methods are reviewed for assessing whether floods may increase in the future. Accounting for feedbacks within the human-water system is important when assessing flood changes over lead times of decades or centuries. It is argued that an integrated flood risk management approach is needed for dealing with future flood risk with a focus on reducing the vulnerability of the societal system. WIREs Water 2015, 2:329-344. doi: 10.1002/wat2.1079 For further resources related to this article, please visit the WIREs website.

  5. Increasing turbine vendor competition in Canada

    Energy Technology Data Exchange (ETDEWEB)

    Magee, J.T. [Emerging Energy Research, Cambridge, MA (United States)


    An overview of the wind turbine market in Canada was presented. Canada is now experiencing increased turbine vendor competition. Trends in wind turbine OEM market shares in Canada have increased from 10 per cent in 2000 to over 70 per cent in 2007. Several major companies in Canada have signed large-scale orders for delivery in 2010. It is expected that future wind turbine demands in all areas of Canada will increase. However, projections for Canadian wind growth demonstrate the difficulties provinces are now facing in trying to attract manufacturing investment away from the United States. Growth in wind turbine investment is in the process of creating a more robust North American wind turbine generator chain. However, the majority of new facilities are located in the United States. It is not known if Quebec's wind turbine generators will be viable outside of fulfilling Hydro-Quebec's tendering process. Canada's wind industry must consider equipment transport costs as well as a shortage of operating and maintenance service infrastructure. It was concluded that growth in the United States is expected to have a positive impact on Canadian wind energy customers. tabs., figs.

  6. Alcoholic Cirrhosis Increases Risk for Autoimmune Diseases

    DEFF Research Database (Denmark)

    Grønbæk, Lisbet; Vilstrup, Hendrik; Deleuran, Bent;


    IRR, 1.56; 95% CI, 1.26-1.92), celiac disease (aIRR, 5.12; 95% CI, 2.58-10.16), pernicious anemia (aIRR, 2.35; 95% CI, 1.50-3.68), and psoriasis (aIRR, 4.06; 95% CI, 3.32-4.97). There was no increase in the incidence rate for rheumatoid arthritis (aIRR, 0.89; 95% CI, 0.69-1.15); the incidence rate......BACKGROUND & AIMS: Alcoholic cirrhosis is associated with hyperactivation and dysregulation of the immune system. In addition to its ability to increase risk for infections, it also may increase the risk for autoimmune diseases. We studied the incidence of autoimmune diseases among patients...... (controls) of the same sex and age. The incidence rates of various autoimmune diseases were compared between patients with cirrhosis and controls and adjusted for the number of hospitalizations in the previous year (a marker for the frequency of clinical examination). RESULTS: Of the 24,679 patients...

  7. Paradoxical sleep deprivation increases plasma endothelin levels

    Directory of Open Access Journals (Sweden)

    B.D. Palma


    Full Text Available The endothelins (ET-1, 2 and 3 constitute a family of 21 amino acid peptides with potent biological activities. ET-1 is one of the most potent endogenous vasoconstrictors so far identified and its increased concentration in plasma appears to be closely related to the pathogenesis of arterial hypertension as well as to obstructive sleep apnea (OSA. OSA patients exhibit repetitive episodes of apnea and hypopnea that result in hypoxia and consecutive arousals. These patients are chronically sleep deprived, which may aggravate the hypertensive features, since literature data show that sleep deprivation results in hypertension both in humans and in animals. Based on the reported relationship between ET-1, hypertension and sleep deprivation consequences, the purpose of the present study was to determine plasma ET concentrations in paradoxical sleep-deprived animals. Male Wistar rats, 3 to 4 months old (N = 10 per group, were deprived of sleep for 24 and 96 h by the platform technique and plasma ET-1/2 was measured by radioimmunoassay. Analysis of plasma revealed that 96 h of sleep deprivation induced a significant increase in ET-1/2 release (6.58 fmol/ml compared to control (5.07 fmol/ml. These data show that sleep deprivation altered plasma ET-1/2 concentrations, suggesting that such an increase may participate in the genesis of arterial hypertension and cardiorespiratory changes observed after sleep deprivation.

  8. Increasing cardiac interventions among the aged.

    LENUS (Irish Health Repository)

    Groarke, J D


    Ireland\\'s over 65 year population is growing. As incidence of coronary events rises with age, there is a growing population of elderly patients with cardiac disease. The changing age profile of patients treated by a tertiary hospital\\'s Cardiology service was quantified using Hospital Inpatient Enquiry data. 53% of CCU admissions were aged > or = 65 years, with admissions aged > or = 85 years in 2008 four times greater than in 2002. Percentages of patients undergoing diagnostic coronary angiography and percutaneous coronary interventions in 1997 aged > or = 70 years were 19% and 18% respectively. By 2007, these percentages had risen to 31% and 34% respectively--greatest increases were in the very elderly age categories. The proportion of ICD recipients aged > 70 years increased from 8% in 2003 to 25% by 2008. The proportion of elderly patients receiving advanced cardiac care is increasing. This trend will continue and has clear resource implications. Outcomes of interventions in the very old need further investigation, since the \\'old old\\' are under-represented in clinical trials.

  9. DDT increases hepatic testosterone metabolism in rats. (United States)

    Sierra-Santoyo, Adolfo; Hernández, Manuel; Albores, Arnulfo; Cebrián, Mariano E


    DDT and its metabolites are considered as endocrine disruptors able to promote hormone-dependent pathologies. We studied the effects of technical-grade DDT on hepatic testosterone metabolism and testosterone hydroxylase activity ratios in the rat. Male and female Wistar rats were treated by gavage with a single dose of technical-grade DDT (0, 0.1, 1, 10, and 100 mg/kg body weight) and killed 24 h later. Hepatic microsomes were incubated with [4-14C]-testosterone and the metabolites were separated by thin-layer chromatography and quantified by radio scanning. DDT increased testosterone biotransformation and modified the profile of metabolites produced in a sex-dependent manner. Males treated with a representative dose (10 mg/kg) produced relatively less androstenedione (AD), 2alpha-hydroxytestosterone (OHT), and 16alpha-OHT but higher 6beta-OHT whereas treated females produced less 7alpha-OHT and AD but higher 6beta-OHT and 6alpha-OHT than their respective controls. In both sexes DDT decreased the relative proportion of AD and increased that of 6beta-OHT suggesting that the androgen-saving pathway was affected. The testosterone 6alpha-/15alpha-OHT ratio, a proposed indicator of demasculinization, was increased in treated males. This effect was in agreement with the demasculinizing ability proposed for DDT. The effects on 6alpha-/16alpha-OHT and 6-dehydrotestosterone/16alpha-OHT ratios followed a similar tendency, with the ratio 6alpha-/16alpha-OHT being the most sensitive marker. Interestingly, these ratios were reduced in treated females suggesting that technical-grade DDT shifted testosterone hydroxylations toward a more masculine pattern. Thus, technical-grade DDT altered the hepatic sexual dimorphism in testosterone metabolism and decreased the metabolic differences between male and female rats.

  10. DDT increases hepatic testosterone metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sierra-Santoyo, Adolfo; Albores, Arnulfo; Cebrian, Mariano E. [Cinvestav-IPN, Seccion de Toxicologia, Mexico (Mexico); Hernandez, Manuel [Cinvestav-IPN, Departamento de Biologia Celular (Mexico)


    DDT and its metabolites are considered as endocrine disruptors able to promote hormone-dependent pathologies. We studied the effects of technical-grade DDT on hepatic testosterone metabolism and testosterone hydroxylase activity ratios in the rat. Male and female Wistar rats were treated by gavage with a single dose of technical-grade DDT (0, 0.1, 1, 10, and 100 mg/kg body weight) and killed 24 h later. Hepatic microsomes were incubated with [4-{sup 14}C]-testosterone and the metabolites were separated by thin-layer chromatography and quantified by radio scanning. DDT increased testosterone biotransformation and modified the profile of metabolites produced in a sex-dependent manner. Males treated with a representative dose (10 mg/kg) produced relatively less androstenedione (AD), 2{alpha}-hydroxytestosterone (OHT), and 16{alpha}-OHT but higher 6{beta}-OHT whereas treated females produced less 7{alpha}-OHT and AD but higher 6{beta}-OHT and 6{alpha}-OHT than their respective controls. In both sexes DDT decreased the relative proportion of AD and increased that of 6{beta}-OHT suggesting that the androgen-saving pathway was affected. The testosterone 6{alpha}-/15{alpha}-OHT ratio, a proposed indicator of demasculinization, was increased in treated males. This effect was in agreement with the demasculinizing ability proposed for DDT. The effects on 6{alpha}-/16{alpha}-OHT and 6-dehydrotestosterone/16{alpha}-OHT ratios followed a similar tendency, with the ratio 6{alpha}-/16{alpha}-OHT being the most sensitive marker. Interestingly, these ratios were reduced in treated females suggesting that technical-grade DDT shifted testosterone hydroxylations toward a more masculine pattern. Thus, technical-grade DDT altered the hepatic sexual dimorphism in testosterone metabolism and decreased the metabolic differences between male and female rats. (orig.)

  11. NASA InterCenter Collaboration Increases ROI (United States)

    Lankford, Kimberly; Best, Susan; Felton, Larry; Newhouse, Marilyn


    Funding for National Aeronautics and Space Administration (NASA) space mission operations is tighter than ever in the current environment of federal government deficit reductions. Conventional wisdom would expect this environment to drive increasing competition between NASA centers for the limited available funds. However, recent inter-center activities at the Huntsville Operations Support Center (HOSC) at NASA's Marshall Space Flight Center emphasize collaboration rather than competition and demonstrate the value of partnerships to increase the return on shrinking investments. These efforts cover a variety of activities and potential returns. To facilitate sharing data from test and verification through operations without levying requirements on data format or software tools, the HOSC is working with multiple centers on an evolutionary path toward a distributed data architecture and archive. The approach reduces the required investment by allowing the partners to reuse their existing formats and tools, while facilitating gone ]stop h user visibility into and controlled access to the full complement of data regardless of user or data location. The HOSC is also working on two activities to promote sharing operations implementations and leveraging the experts and expertise across multiple NASA sites. In one, the use of Consultative Committee for Space Data Systems (CCSDS) standards for the message abstraction layer provides an interoperability layer on top of existing ground data system communication architectures. This allows missions to select the most appropriate solutions for their requirements with a minimal investment in rehosting the components in a coherent operational environment. The other emphasizes shared tools and increased remote access to minimize travel for tests and critical activities and reduce the floor space required for a dedicated operations center. This paper summarizes these and other inter-center collaboration activities at the HOSC and the

  12. Interventions for increasing uptake in screening programmes

    Directory of Open Access Journals (Sweden)

    Droste, Sigrid


    Full Text Available Introduction: Opportunities for the early detection of disease are not sufficiently being taken advantage of. Specific interventions could increase the uptake of prevention programmes. A comprehensive analysis of effectiveness and cost-effectiveness of these interventions with reference to Germany is still needed. Objectives: This report aimed to describe and assess interventions to increase uptake in primary and secondary prevention and to explore the assessment of their cost-effectiveness. Methods: 29 scientific databases were systematically searched in a wide strategy. Additional references were located from bibliographies. All published systematic reviews and primary studies were assessed for inclusion without language restrictions. Teams of two reviewers identified the literature, extracted data and assessed the quality of the publications independently. Results: Four HTA reports and 22 systematic reviews were identified for the medical evaluation covering a variety of interventions. The economic evaluation was based on two HTA-reports, one meta-analysis and 15 studies. The evidence was consistent for the effectiveness of invitations and reminders aimed at users, and for prompts aimed at health care professionals. These interventions were the most commonly analysed. (Financial Incentives for users and professionals were identified in a small number of studies. Limited evidence was available for cost-effectiveness showing incremental costs for follow-up reminders and invitations by telephone. Evidence for ethical, social and legal aspects pointed to needs in vulnerable populations. Discussion: The material was heterogeneous regarding interventions used, study populations and settings. The majority of references originated from the United States and focused on secondary prevention. Approaching all target groups by invitations and reminders was recommended to increase uptake in prevention programmes in general. Conclusions: Further research

  13. Nanolaminates: increasing dielectric breakdown strength of composites. (United States)

    Fillery, Scott P; Koerner, Hilmar; Drummy, Lawrence; Dunkerley, Erik; Durstock, Michael F; Schmidt, Daniel F; Vaia, Richard A


    Processable, low-cost, high-performance hybrid dielectrics are enablers for a vast array of green technologies, including high-temperature electrical insulation and pulsed power capacitors for all-electric transportation vehicles. Maximizing the dielectric breakdown field (E(BD)), in conjunction with minimization of leakage current, directly impacts system performance because of the field's quadratic relationship with electrostatic energy storage density. On the basis of the extreme internal interfacial area and ultrafine morphology, polymer-inorganic nanocomposites (PNCs) have demonstrated modest increases in E(BD) at very low inorganic loadings, but because of insufficient control of the hierarchal morphology of the blend, have yielded a precipitous decline in E(BD) at intermediate and high inorganic volume fractions. Here in, we demonstrate that E(BD) can be increased up to these intermediate inorganic volume fractions by creating uniform one-dimensional nanocomposites (nanolaminates) rather than blends of spherical inorganic nanoparticles and polymers. Free standing nanolaminates of highly aligned and dispersed montmorillonite in polyvinyl butyral exhibited enhancements in E(BD) up to 30 vol % inorganic (70 wt % organically modified montmorillonite). These relative enhancements extend up to five times the inorganic fraction observed for random nanoparticle dispersions, and are anywhere from two to four times greater than observed at comparable volume fraction of nanoparticles. The breakdown characteristics of this model system suggested a trade-off between increased path tortuosity and polymer-deficient structural defects. This implies that an idealized PNC morphology to retard the breakdown cascade perpendicular to the electrodes will occur at intermediate volume fractions and resemble a discotic nematic phase where highly aligned, high-aspect ratio nanometer thick plates are uniformly surrounded by nanoscopic regions of polymer.

  14. AGU Journals Increase Speed and Impact (United States)

    Warner, Mary


    Fast publication and high quality and impact are important for effective dissemination of geoscience research. With this in mind, AGU's journal editors and staff, along with staff at our publishing partner, Wiley, have been working to increase both the speed of publication and the impact of the research published in our 18 peer-reviewed journals while maintaining our commitment to quality. Significant progress continues to be made on both fronts, as evidenced by the most recent publication times and the 2013 release of the Journal Citation Reports®, which was issued by Thomson Reuters on 29 July.

  15. Emerin increase in regenerating muscle fibers

    Directory of Open Access Journals (Sweden)

    S Squarzoni


    Full Text Available The fate of emerin during skeletal muscle regeneration was investigated in an animal model by means of crush injury. Immunofluorescence, immunoblotting and mRNA analysis demonstrated that emerin level is increased in regenerating rat muscle fibers with respect to normal mature myofibers. This finding suggests an involvement of emerin during the muscle fiber regeneration process, in analogy with its reported involvement in muscle cell differentiation in vitro. The impairment of skeletal muscle physiological regeneration or reorganization could be a possible pathogenetic mechanism for Emery Dreifuss muscular dystrophy.

  16. Increase in flexibility with latest technologies

    Energy Technology Data Exchange (ETDEWEB)

    Fuebi, Michael; Krull, Florian Felix [RWE Technology GmbH, Essen (Germany); Ladwig, Michael [Alstom (Switzerland) AG, Baden (Switzerland)


    Flexibility demands on conventional power plants rise to ensure grid stability within a power generation mix with drastically increasing capacities of renewable power generation sources such as wind farms and photovoltaics. In this paper flexibility requirements for a power plant portfolio are discussed. Through selected examples of projects from RWE's current investment programme, comprising around 13 GW of efficient and flexible power plant capacity in Germany, the Netherlands, Turkey and the UK, application of the latest technologies to fulfil flexibility requirements is presented. Further, the potential of smart retrofits in terms of combined flexibility and efficiency gains is illustrated by means of an existing power plant unit retrofit project. (orig.)

  17. Homocysteine increases the risk associated with hyperlipidaemia.

    LENUS (Irish Health Repository)

    Daly, Caroline


    The European Concerted Action Project \\'Homocysteine and Vascular Disease\\' showed that an elevated homocysteine is associated with a substantially increased risk of cardiovascular disease, and particularly when combined with other factors such as smoking, hypertension and hypercholesterolaemia. The purpose of this study was to examine the potential interactions between homocysteine and individual lipid subfractions. In addition, it was hypothesized that HDL cholesterol may protect against hyperhomocysteinaemia because HDL cholesterol is associated with the enzyme paroxonase, which reduces oxidization of homocysteine to the harmful metabolite, homocysteine thiolactonase.

  18. Timelike curves can increase entanglement with LOCC (United States)

    Moulick, Subhayan Roy; Panigrahi, Prasanta K.


    We study the nature of entanglement in presence of Deutschian closed timelike curves (D-CTCs) and open timelike curves (OTCs) and find that existence of such physical systems in nature would allow us to increase entanglement using local operations and classical communication (LOCC). This is otherwise in direct contradiction with the fundamental definition of entanglement. We study this problem from the perspective of Bell state discrimination, and show how D-CTCs and OTCs can unambiguously distinguish between four Bell states with LOCC, that is otherwise known to be impossible.

  19. Does getting a dog increase recreational walking?

    Directory of Open Access Journals (Sweden)

    Knuiman Matthew W


    Full Text Available Abstract Background This study examines changes in socio-demographic, environmental and intrapersonal factors associated with dog acquisition in non-dog owners at baseline to 12-months follow-up and the effect of dog acquisition on minutes per week of recreational walking. Methods RESIDE study participants completed self-administered questionnaires (baseline and 12-months follow-up measuring physical activity, dog ownership, dog walking behavior as well as environmental, intrapersonal and socio-demographic factors. Analysis was restricted to 'Continuing non-owners' (i.e., non-owners at both baseline and follow-up; n = 681 and 'New dog owners' (i.e., non-owners who acquired a dog by follow-up; n = 92. Results Overall, 12% of baseline non-owners had acquired a dog at follow-up. Dog acquisition was associated with working and having children at home. Those who changed from single to couple marital status were also more likely to acquire a dog. The increase in minutes of walking for recreation within the neighborhood from baseline to follow-up was 48 minutes/week for new dog owners compared with 12 minutes/week for continuing non-owners (p p p > 0.05 after further adjustment for change in baseline to follow-up variables. Increase in intention to walk was the main factor contributing to attenuation of the effect of dog acquisition on recreational walking. Conclusion This study used a large representative sample of non-owners to examine the relationship between dog acquisition and recreational walking and provides evidence to suggest that dog acquisition leads to an increase in walking. The most likely mechanism through which dog acquisition facilitates increased physical activity is through behavioral intention via the dog's positive effect on owner's cognitive beliefs about walking, and through the provision of motivation and social support for walking. The results suggest that behavioral intention mediates the relationship between dog acquisition

  20. Steps toward increasing Q in mirror systems

    Energy Technology Data Exchange (ETDEWEB)

    Post, R.F.


    Experiments such as the 2XIIB experiment at Livermore have established the ability of mirror systems to confine high temperature, high density plasmas at central beta values exceeding unity. Given these results the next tasks for the mirror approach are to explore means for increasing the energy gain factor Q and to scale up the plasma volume, both of these requirements deriving from economic constraints. This report discusses means for increasng Q, including recent improvements in the tandem mirror concept and design studies of the field-reversed mirror in the context of upcoming and proposed scaled-up mirror experiments.

  1. Infection increases mortality in necrotizing pancreatitis

    DEFF Research Database (Denmark)

    Werge, Mikkel; Novovic, Srdan; Schmidt, Palle N


    OBJECTIVES: To assess the influence of infection on mortality in necrotizing pancreatitis. METHODS: Eligible prospective and retrospective studies were identified through manual and electronic searches (August 2015). The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Meta...... sterile necrosis and organ failure was associated with a mortality of 19.8%. If the patients had infected necrosis without organ failure the mortality was 1.4%. CONCLUSIONS: Patients with necrotizing pancreatitis are more than twice as likely to die if the necrosis becomes infected. Both organ failure...... and infected necrosis increase mortality in necrotizing pancreatitis....

  2. The public economics of increasing longevity



    One of the greatest success stories in our societies is that people are living longer, life expectancy at birth being now above 80 years. Whereas the lengthening of life opens huge opportunities for individuals if extra years are spent in prosperity and good health, it is however often regarded as a source of problems for policy-makers. The goal of this paper is to examine the key policy challenges raised by increasing longevity. For that purpose, we first pay attention to the representation ...

  3. China Onshore Oil Production Increasing Steadily

    Institute of Scientific and Technical Information of China (English)

    Tian Xueyi


    @@ China onshore oil industry made a considerable achievement in 1994 on the basis of developing successively for many years and oil and gas production increasing year after year. Annual crude production reached 139.44 million tons. In the first half of last year, imported crude and finished product has been out of control and oil product has been unsalable so that some oil wells have to be closed and off production in Xinjiang and Daqing. Crude production reduced by 1.28 million tons in total.

  4. Barriers to increased market-oriented activity

    DEFF Research Database (Denmark)

    Bisp, Søren


    Most research on market orientation has dealt with assessing how market orientation behaviour is related to business performance. This work has established an intense market-oriented activity as significantly and positively related to business performance under most circumstances. In a maturing...... and related activities still seem to attract relatively few resources is not answered by supplying another checklist or package of facilitators. Based on published conceptual writings and empirical studies this article makes an account of what the intra-organizational barriers may be to increased market...

  5. Final Technical Report: Increasing Prediction Accuracy.

    Energy Technology Data Exchange (ETDEWEB)

    King, Bruce Hardison [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hansen, Clifford [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Stein, Joshua [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    PV performance models are used to quantify the value of PV plants in a given location. They combine the performance characteristics of the system, the measured or predicted irradiance and weather at a site, and the system configuration and design into a prediction of the amount of energy that will be produced by a PV system. These predictions must be as accurate as possible in order for finance charges to be minimized. Higher accuracy equals lower project risk. The Increasing Prediction Accuracy project at Sandia focuses on quantifying and reducing uncertainties in PV system performance models.

  6. China to Increase Oil Processing Capacity Sharply

    Institute of Scientific and Technical Information of China (English)

    Shao Wenjing


    @@ China plans to raise its annual crude oil processing capacity to 405 million tons by 2011 in the efforts to implement its restructuring and stimulus plans for the petrochemical industry. This will represent an increase of about 18.4 percent over its processing volume last year,which topped 342.1 million tons, according to the figures from National Bureau of Statistics. China is scheduled to build three to four major oil refining plants in the Yangtze River Delta in eastern China and the Pearl River Delta in southern China by 2011. Each plant would be capable of processing 20 million tons of oil annually.

  7. Apparent speed increases at low luminance


    Vaziri-Pashkam, Maryam; Cavanagh, Patrick


    To investigate the effect of luminance on apparent speed, subjects adjusted the speed of a low-luminance rotating grating (0.31 cd/m2) to match that of a high-luminance one (1260 cd/m2). Above 4 Hz, subjects overestimated the speed of the low-luminance grating. This overestimation increased as a function of temporal rate and reached 30% around 10 Hz temporal rates. The speed overestimation became significant once the lower luminance was 2.4 log units lower than the high luminance comparison. ...

  8. Global warming without global mean precipitation increase?


    Salzmann, Marc


    Global climate models simulate a robust increase of global mean precipitation of about 1.5 to 2% per kelvin surface warming in response to greenhouse gas (GHG) forcing. Here, it is shown that the sensitivity to aerosol cooling is robust as well, albeit roughly twice as large. This larger sensitivity is consistent with energy budget arguments. At the same time, it is still considerably lower than the 6.5 to 7% K−1 decrease of the water vapor concentration with cooling from anthropogenic aeroso...

  9. Increasing certification through unit-based education. (United States)

    Fischer-Cartlidge, Erica; Mahon, Suzanne


    Certification has been identified by multiple organizations as an important component and means of elevating the level of nursing care provided to patients and demonstrating to the public that the nursing staff has subspecialty knowledge. Certification may lead to improved patient satisfaction and outcomes as well as increased nurse satisfaction and retention. Despite the known potential benefits associated with certification, institutions struggle to improve certification rates. One possible method to overcome system barriers to certification is the implementation of a unit-based study course to prepare nurses for the Certified Breast Care Nurse (CBCN) examination. Data collected by an author-developed tool as one institution created and executed a unit-based study course suggest that such an approach increased certification rates and improved disease-specific knowledge and confidence among the staff, despite no official data existing on the tool's reliability and validity. Implementation of similar programs may be successful in improving certification at other institutions seeking to raise certification rates.

  10. [Increasing difficulties for scientific publication in Venezuela]. (United States)

    Ryder, Elena


    A very important increase in the costs of the edition of scientific journals has taken place in Venezuela, due to difficulties in obtaining imported free acid paper and other materials used for handling documents. Like other journals, Investigaci6n Clinica has been considering switching completely to a digital publication format; however there are several reasons that prevent us to doing it at this time: the journal is distributed in printed form to many national institutions, which do not have immediate access to digital information. In addition, there exists a commitment of shipment of printed issues for some international indices and in exchange with other national and foreign journals, whose printed format we receive. Another important aspect is that our University maintains a weak technological platform that makes difficult the immediacy required for the interchange with authors and consulted referees of received papers; and there is a latent danger of limitations in the use of digital technologies, due to current national politic problems. Consequently, we need to continue with the printed format, but must reduce the amount of printed issues, so as not to limit the number of papers published in each edition. Nevertheless, there is an ever increasing number of contributions from foreign researches and Investigaci6n Clinica has been recently included in two new international indices, the SEIIC from Argentina and the Infobase Index from India, reasons that obligate us to maintain our levels of excellence and commitment to our authors and readers.

  11. Increased serum prolactin in borderline personality disorder. (United States)

    Atmaca, Murad; Korkmaz, Sevda; Ustundag, Bilal; Ozkan, Yusuf


    Although there is an important interaction between serotonergic system, prolactin and suicidal behavior, and impulsivity, no investigation examined the prolactin values in borderline personality disorder in which suicidal behavior and impulsivity are core symptom dimensions. In this context, in the present investigation, we planned to measure serum prolactin levels in the patients with borderline personality disorder. The study comprised 15 patients with borderline personality disorder and 15 healthy controls. Prolactin values were measured in both patients and control subjects. The patients had abnormally higher mean value of prolactin compared to those of healthy controls (48.66 ± 36.48 mg/dl for patients vs. 15.20 ± 7.81 mg/dl for healthy controls). There was no correlation between prolactin values and any demographic variables for both the patients and control subjects. In conclusion, our present results suggest that prolactin values increased in the patients with borderline personality disorder and are required to be replicated by more comprehensive and detailed further studies to decipher the exact roles of prolactin increase.

  12. Increased chondrocyte adhesion on nanotubular anodized titanium. (United States)

    Burns, Kevin; Yao, Chang; Webster, Thomas J


    Previous studies have demonstrated increased osteoblast (bone-forming cells) functions (including adhesion, synthesis of intracellular collagen, alkaline phosphatase activity, and deposition of calcium-containing minerals) on titanium anodized to possess nanometer features compared with their unanodized counterparts. Such titanium materials were anodized to possess novel nanotubes also capable of drug delivery. Since titanium has not only experienced wide spread commercial use in orthopedic but also in cartilage applications, the objective of the present in vitro study was for the first time to investigate chondrocyte (cartilage synthesizing cells) functions on titanium anodized to possess nanotubes. For this purpose, titanium was anodized in dilute hydrofluoric acid at 20 V for 20 min. Results showed increased chondrocyte adhesion on anodized titanium with nanotube structures compared with unanodized titanium. Importantly, the present study also provided evidence why. Since material characterization studies revealed significantly greater nanometer roughness and similar chemistry as well as crystallinity between nanotubular anodized and unanodized titanium, the results of the present study highlight the importance of the nanometer roughness provided by anodized nanotubes on titanium for enhancing chondrocyte adhesion. In this manner, the results of the present in vitro study indicated that anodization might be a promising quick and inexpensive method to modify the surface of titanium-based implants to induce better chondrocyte adhesion for cartilage applications.

  13. Violence against abortion increases in US clinics. (United States)

    Roberts, J


    In the US, violence against abortion clinics is escalating. In July 1994, a doctor who performed abortions and one of his escorts was gunned down outside of an abortion clinic. In March of 1993, another doctor was killed outside of a clinic. That killing prompted passage of a federal law designed to protect abortion providers and clinics from violence. In addition to the individuals murdered, the number of violent incidents against abortion clinics increased four-fold to 250 in 1993. Some elderly physicians feel compelled to continue to perform the procedure instead of retiring because there are no young practitioners to replace them. These physicians note that the young practitioners have no experience with the deaths and illness which resulted from illegal abortions and have not been properly trained by their medical schools. The US Attorney General has dispatched federal marshalls to guard abortion clinics, and local police are increasing their protection of clinics. Abortion protestors say that the new federal law will cause some formerly peaceful protestors to resort to violence.

  14. Increased biogas production using microbial stimulants. (United States)

    Singh, S; Kumar, S; Jain, M C; Kumar, D


    Laboratory studies were undertaken to evaluate the effect of microbial stimulants Aquasan and Teresan, on biogas yields from cattle dung and combined residues of cattle dung and kitchen waste, respectively. The addition of single dose of Aquasan at the rate of 10, 15 and 20 ppm to cattle dung on the first day of incubation resulted in increased gas yields ranging between 45.1 and 62.1 l/kg dry matter. Subsequent addition of Aquasan at 15 and 20 ppm dosage after a period of 15 days increased the gas yields by 15-16%. The gas production was found to be optimum at a dosage level of 15 ppm and was 39% and 55% higher with single and dual additions, respectively, than untreated cattle dung. In another bench scale study (1:1 dry matter) the addition of Teresan at 10 ppm concentration to the mixed residues of cattle dung and kitchen wastes at different solids concentration, produced 34.8% more gas (272.4 l/kg d.m.) than the uninoculated mixture at 15% TS concentration (202.4 l/kg d.m.).

  15. Increasing women in leadership in global health. (United States)

    Downs, Jennifer A; Reif, Lindsey K; Hokororo, Adolfine; Fitzgerald, Daniel W


    Globally, women experience a disproportionate burden of disease and death due to inequities in access to basic health care, nutrition, and education. In the face of this disparity, it is striking that leadership in the field of global health is highly skewed towards men and that global health organizations neglect the issue of gender equality in their own leadership. Randomized trials demonstrate that women in leadership positions in governmental organizations implement different policies than men and that these policies are more supportive of women and children. Other studies show that proactive interventions to increase the proportion of women in leadership positions within businesses or government can be successful. Therefore, the authors assert that increasing female leadership in global health is both feasible and a fundamental step towards addressing the problem of women's health. In this Perspective, the authors contrast the high proportion of young female trainees who are interested in academic global health early in their careers with the low numbers of women successfully rising to global health leadership roles. The authors subsequently explore reasons for female attrition from the field of global health and offer practical strategies for closing the gender gap in global health leadership. The authors propose solutions aimed to promote female leaders from both resource-wealthy and resource-poor countries, including leadership training grants, mentorship from female leaders in global professions, strengthening health education in resource-poor countries, research-enabling grants, and altering institutional policies to support women choosing a global health career path.

  16. Environmental implications of increased biomass energy use

    Energy Technology Data Exchange (ETDEWEB)

    Miles, T.R. Sr.; Miles, T.R. Jr. (Miles (Thomas R.), Portland, OR (United States))


    This study reviews the environmental implications of continued and increased use of biomass for energy to determine what concerns have been and need to be addressed and to establish some guidelines for developing future resources and technologies. Although renewable biomass energy is perceived as environmentally desirable compared with fossil fuels, the environmental impact of increased biomass use needs to be identified and recognized. Industries and utilities evaluating the potential to convert biomass to heat, electricity, and transportation fuels must consider whether the resource is reliable and abundant, and whether biomass production and conversion is environmentally preferred. A broad range of studies and events in the United States were reviewed to assess the inventory of forest, agricultural, and urban biomass fuels; characterize biomass fuel types, their occurrence, and their suitability; describe regulatory and environmental effects on the availability and use of biomass for energy; and identify areas for further study. The following sections address resource, environmental, and policy needs. Several specific actions are recommended for utilities, nonutility power generators, and public agencies.

  17. Increased mortality in hypernatremic burned patients

    Directory of Open Access Journals (Sweden)

    Lange, Thomas


    Full Text Available Introduction: In-hospital hypernatremia develops usually iatrogenically from inadequate or inappropriate fluid prescription. In severely burned patient an extensive initial fluid resuscitation is necessary for burn shock survival. After recovering of cellular integrity the circulating volume has to be normalized. Hereby extensive water and electrolyte shifts can provoke hypernatremia. Purpose: Is a hypernatremic state associated with increased mortality? Method: Retrospective study for the incidence of hypernatremia and survival in 40 patients with a totally burned surface area (TBSA >10%. Age, sex, TBSA, ABSI-Score and fluid resuscitation within the first 24 hours were analyzed. Patients were separated in two groups without (Group A or with (Group B hypernatremia. Results: Hypernatremia occurred on day 5±1.4. No significant difference for age, sex, TBSA, ABSI-Score and fluid resuscitation within the first 24 hours were calculated. In Group A all patients survived, while 3 of the hypernatremic patient in Group B died during ICU-stay (Odds-ratio = 1.25; 95% CI 0.971–1.61; p=0.046. Conclusion: Burned patients with an in-hospital acquired hypernatremia have an increased mortality risk. In case of a hypernatremic state early intervention is obligatory. There is a need of a fluid removal strategy in severely burned patient to avoid water imbalance.

  18. Osteoporosis: an increasing concern in pediatric dentistry. (United States)

    da Fonseca, Marcio A


    Increasing numbers of children are being affected by low bone density and osteoporosis. Bone fractures are the main reason for hospitalization between 10 and 14 years of age and, over the past 3 decades, there has been an increase in the incidence of fractures in children. Childhood factors such as lifestyle, diet, chronic illness, and medications have a vital short-term impact on bone health and a long-term effect on the achievement of peak bone mass, with the potential for morbidity in adulthood. The primary forms of osteoporosis consist of rare inherited conditions, but the secondary forms are becoming more common given that chronically ill children are surviving longer. This subject should be of interest to pediatric dentists, because low mineral density and osteoporosis, together with drugs used to treat them (eg, bisphosphonates), may cause adverse effects in the oral cavity. Furthermore, the pediatric dentist is an important health care professional to counsel patients about healthy lifestyles that can help prevent the condition from an early age.

  19. Estradiol increases the anorexia associated with increased 5-HT2C receptor activation in ovariectomized rats


    Rivera, Heidi M.; Santollo, Jessica; Nikonova, Larissa V.; Eckel, Lisa A.


    Estradiol’s inhibitory effect on food intake is mediated, in part, by its ability to increase the activity of meal-related signals, including serotonin (5-HT), which hasten satiation. The important role that postsynaptic 5-HT2C receptors play in mediating 5-HT’s anorexigenic effect prompted us to investigate whether a regimen of acute estradiol treatment increases the anorexia associated with increased 5-HT2C receptor activation in ovariectomized (OVX) rats. We demonstrated that intraperitone...

  20. Cloud albedo increase from carbonaceous aerosol

    Directory of Open Access Journals (Sweden)

    W. R. Leaitch


    Full Text Available Airborne measurements from two consecutive days, analysed with the aid of an aerosol-adiabatic cloud parcel model, are used to study the effect of carbonaceous aerosol particles on the reflectivity of sunlight by water clouds. The measurements, including aerosol chemistry, aerosol microphysics, cloud microphysics, cloud gust velocities and cloud light extinction, were made below, in and above stratocumulus over the northwest Atlantic Ocean. On the first day, the history of the below-cloud fine particle aerosol was marine and the fine particle sulphate and organic carbon mass concentrations measured at cloud base were 2.4 μg m−3 and 0.9 μg m−3 respectively. On the second day, the below-cloud aerosol was continentally influenced and the fine particle sulphate and organic carbon mass concentrations were 2.3 μg m−3 and 2.6 μg m−3 respectively. Over the range 0.06–0.8 μm diameter, the shapes of the below-cloud size distributions were similar on both days and the number concentrations were approximately a factor of two higher on the second day. The cloud droplet number concentrations (CDNC on the second day were approximately three times higher than the CDNC measured on the first day. Using the parcel model to separate the influence of the differences in gust velocities, we estimate from the vertically integrated cloud light scattering measurements a 6% increase in the cloud albedo principally due to the increase in the carbonaceous components on the second day. Assuming no additional absorption by this aerosol, a 6% albedo increase translates to a local daytime radiative cooling of ∼12 W m−2. This result provides observational evidence that the role of anthropogenic carbonaceous components in the cloud albedo effect can be much larger than that of anthropogenic sulphate, as some global simulations have indicated.

  1. Robust Increased Capacity Image Steganographic Scheme

    Directory of Open Access Journals (Sweden)

    M. Khurrum Rahim Rashid


    Full Text Available with the rising tempo of unconventional right to use and hit protection of secret information is of extreme value. With the rising tempo of unconventional right to use and hit, protection of secret information is of extreme value. Steganography is the vital matter in information hiding. Steganography refers to the technology of hiding data into digital media without depiction of any misgiving. Lot of techniques has been projected during past years. In this paper, a new steganography approach for hiding data in digital images is presented with a special feature that it increases the capacity of hiding data in digital images with the least change in images perceptual appearance and statistical properties at too much less level which will be very difficult to detect.

  2. Increasing productivity through Total Reuse Management (TRM) (United States)

    Schuler, M. P.


    Total Reuse Management (TRM) is a new concept currently being promoted by the NASA Langley Software Engineering and Ada Lab (SEAL). It uses concepts similar to those promoted in Total Quality Management (TQM). Both technical and management personnel are continually encouraged to think in terms of reuse. Reuse is not something that is aimed for after a product is completed, but rather it is built into the product from inception through development. Lowering software development costs, reducing risk, and increasing code reliability are the more prominent goals of TRM. Procedures and methods used to adopt and apply TRM are described. Reuse is frequently thought of as only being applicable to code. However, reuse can apply to all products and all phases of the software life cycle. These products include management and quality assurance plans, designs, and testing procedures. Specific examples of successfully reused products are given and future goals are discussed.

  3. Increased mortality among people with anxiety disorders

    DEFF Research Database (Denmark)

    Meier, Sandra M; Mattheisen, Manuel; Mors, Ole;


    BACKGROUND: Anxiety disorders and depression are the most common mental disorders worldwide and have a striking impact on global disease burden. Although depression has consistently been found to increase mortality; the role of anxiety disorders in predicting mortality risk is unclear. AIMS......: To assess mortality risk in people with anxiety disorders. METHOD: We used nationwide Danish register data to conduct a prospective cohort study with over 30 million person-years of follow-up. RESULTS: In total, 1066 (2.1%) people with anxiety disorders died during an average follow-up of 9.7 years....... The risk of death by natural and unnatural causes was significantly higher among individuals with anxiety disorders (natural mortality rate ratio (MRR) = 1.39, 95% CI 1.28-1.51; unnatural MRR = 2.46, 95% CI 2.20-2.73) compared with the general population. Of those who died from unnatural causes, 16.5% had...

  4. How to Increase Correct Learning of Astronomy (United States)

    Hojaev, Alisher S.

    Astronomy is the most popular and attractive among the sciences. Undoubtedly the importance of exact knowledge of astronomy is becoming more and more important. However the level of teaching of astronomy at schools lyceums colleges and even universities especially in the FSU countries is far to be satisfactorily. Moreover some astronomy related information in the mass media (TV newspapersetc.) has often an incorrect statements. We see the key role of astronomical organizations and each of astronomers in an application of the correct knowledge in the curriculum popularization and control of the astronomical presentations in the mass media. The wide spreading of the Internet recently having place particularly in Uzbekistan gives a new possibilities for increase the learning of astronomy utilize the remote education tools open new frontiers for wide popularization of astronomy. The arrangement of practical excursions public lectures and presentations of the news in astronomy held in UBAI is discussed. Some other idea to improve are given.

  5. Prodrug Approach for Increasing Cellular Glutathione Levels

    Directory of Open Access Journals (Sweden)

    Ivana Cacciatore


    Full Text Available Reduced glutathione (GSH is the most abundant non-protein thiol in mammalian cells and the preferred substrate for several enzymes in xenobiotic metabolism and antioxidant defense. It plays an important role in many cellular processes, such as cell differentiation, proliferation and apoptosis. GSH deficiency has been observed in aging and in a wide range of pathologies, including neurodegenerative disorders and cystic fibrosis (CF, as well as in several viral infections. Use of GSH as a therapeutic agent is limited because of its unfavorable biochemical and pharmacokinetic properties. Several reports have provided evidence for the use of GSH prodrugs able to replenish intracellular GSH levels. This review discusses different strategies for increasing GSH levels by supplying reversible bioconjugates able to cross the cellular membrane more easily than GSH and to provide a source of thiols for GSH synthesis.

  6. Trust in a Time of Increasing Diversity

    DEFF Research Database (Denmark)

    Dinesen, Peter Thisted; Sønderskov, Kim Mannemar


    In this study, we examine the impact of ethnic diversity in Danish municipalities on citizens’ social trust over the last three decades. During this period, Danish society has grown increasingly ethnically diverse, and this begs the question whether this has influenced trust in others negatively....... Existing evidence from the Anglo-Saxon countries would suggest that this is the case, whereas evidence from the European continent mainly suggests that no link exists between ethnic diversity and social trust. The empirical analysis uses individual-level data on social trust from several surveys in Denmark...... in the period from 1979 to 2009 coupled with diversity at the municipality level. Individual-level measures of trust over time enable us to estimate the impact on social trust of changes in ethnic diversity within municipalities and, we argue, thereby obtain a more precise estimate of the effect of ethnic...

  7. How retailer coupons increase attitudinal loyalty –

    DEFF Research Database (Denmark)

    Wierich, Ralf; Zielke, Stephan


    modeling. Findings – The results demonstrate that addressing customers personally and face value have a positive impact on attitudinal loyalty. Surprisingly, the positive effect of personalization is stronger than that of typical variations in face value. In contrast, a high minimum purchase amount......Purpose – The aim of this paper is to investigate how different design elements of retailer coupons increase the attitudinal loyalty towards retailers. Design/methodology/approach – Three design elements are manipulated in a 2x2x2 experimental design. Data is analysed using structural equation...... restriction has a negative total effect on loyalty and neutralizes the positive effects generated by personalization. The results illustrate further that personalization influences loyalty via self-reference and enjoyment independently of any cognitive evaluation of the coupon, while face value...

  8. Hypoxemia increases serum interleukin-6 in humans

    DEFF Research Database (Denmark)

    Klausen, T; Olsen, Niels Vidiendal; Poulsen, T D


    Serum concentrations of interleukin (IL) 1 beta, IL-1 receptor antagonist (IL-1ra), IL-6, tumor necrosis factor (TNF) alpha, and C-reactive protein (CRP) were determined in ten healthy men at sea level and during four days of altitude hypoxia (4350m above sea level). The mean (SD) arterial blood...... oxygen saturations were 78.6 (7.3)%, 82.4 (4.9)%, and 83.4 (5.3)% in the first, second, and third days at altitude, respectively. A symptom score of acute mountain sickness (AMS) revealed that the subjects had mostly light symptoms of AMS. Mean serum IL-6 increased from 1.36 (1.04) pg x ml(-1) at sea...

  9. Impacts of increasing ozone on Indian plants. (United States)

    Oksanen, E; Pandey, V; Pandey, A K; Keski-Saari, S; Kontunen-Soppela, S; Sharma, C


    Increasing anthropogenic and biogenic emissions of precursor compounds have led to high tropospheric ozone concentrations in India particularly in Indo-Gangetic Plains, which is the most fertile and cultivated area of this rapidly developing country. Current ozone risk models, based on European and North American data, provide inaccurate estimations for crop losses in India. During the past decade, several ozone experiments have been conducted with the most important Indian crop species (e.g. wheat, rice, mustard, mung bean). Experimental work started in natural field conditions around Varanasi area in early 2000's, and the use of open top chambers and EDU (ethylene diurea) applications has now facilitated more advanced studies e.g. for intra-species sensitivity screening and mechanisms of tolerance. In this review, we identify and discuss the most important gaps of knowledge and future needs of action, e.g. more systematic nationwide monitoring for precursor and ozone formation over Indian region.

  10. Wind Stress Increases Glacial Atlantic Overturning (United States)

    Muglia, J.; Schmittner, A.


    Previous Paleoclimate Model Intercomparison Project (PMIP) simulations of the Last Glacial Maximum (LGM) Atlantic Meridional Overturning Circulation (AMOC) showed ambiguous results on transports and structure. Here we analyze the most recent PMIP3 models, which show a consistent increase (on average by 41%) and deepening (580 m) of the AMOC for all models with respect to pre-industrial control (PIC) simulations (see Figure), in contrast to some reconstructions. Changes in wind stress alone lead to similar AMOC responses in a climate-ocean circulation model, suggesting that atmospheric circulation changes in the North Atlantic due to the presence of ice sheets are an important control in the PMIP3 models' LGM response. These results improve our understanding of the LGM AMOC's driving forces and are relevant for the evaluation of models that are used in the IPCC's Assessment Reports for future climate projections, as well as for the currently ongoing design of the next round of PMIP.

  11. Hollow rhodoliths increase Svalbard's shelf biodiversity (United States)

    Teichert, Sebastian


    Rhodoliths are coralline red algal assemblages that commonly occur in marine habitats from the tropics to polar latitudes. They form rigid structures of high-magnesium calcite and have a good fossil record. Here I show that rhodoliths are ecosystem engineers in a high Arctic environment that increase local biodiversity by providing habitat. Gouged by boring mussels, originally solid rhodoliths become hollow ecospheres intensely colonised by benthic organisms. In the examined shelf areas, biodiversity in rhodolith-bearing habitats is significantly greater than in habitats without rhodoliths and hollow rhodoliths yield a greater biodiversity than solid ones. This biodiversity, however, is threatened because hollow rhodoliths take a long time to form and are susceptible to global change and anthropogenic impacts such as trawl net fisheries that can destroy hollow rhodoliths. Rhodoliths and other forms of coralline red algae play a key role in a plurality of environments and need improved management and protection plans.

  12. Increasing sensing resolution with error correction. (United States)

    Arrad, G; Vinkler, Y; Aharonov, D; Retzker, A


    The signal to noise ratio of quantum sensing protocols scales with the square root of the coherence time. Thus, increasing this time is a key goal in the field. By utilizing quantum error correction, we present a novel way of prolonging such coherence times beyond the fundamental limits of current techniques. We develop an implementable sensing protocol that incorporates error correction, and discuss the characteristics of these protocols in different noise and measurement scenarios. We examine the use of entangled versue untangled states, and error correction's reach of the Heisenberg limit. The effects of error correction on coherence times are calculated and we show that measurement precision can be enhanced for both one-directional and general noise.

  13. All-Round Marketing Increases Hospital Popularity. (United States)

    Ziqi, Tao


    Xuzhou Center Hospital is in a competing medical market in Xuzhou city. This hospital has been dedicating to improve the medical skills and provide professional and individualized service to the patients in order to improve the patient's experience and increase the patient's satisfaction. On the other side, this hospital has provided an all-round marketing campaign to build up the social influence and public reputation through public-praise marketing, web marketing, media marketing, and scholar marketing. Besides, this hospital has been cooperating with foreign medical institutions and inviting foreign medical specialists to academic communication. With the combined effects of improving medical service and all-round marketing, the hospital's economic performance has been enhanced significantly and laid a solid foundation for its ambition to become the first-class hospital in Huaihai Economic Zone.

  14. Can a sense of entitlement increase stealing?

    DEFF Research Database (Denmark)

    Gravert, Christina Annette

    was asked to roll a die to determine their payoff, while the other group had three minutes to find matching numbers in a matrix task. Participants then paid themselves unobserved by the experimenter. I find that the participants who earned their payoff according to performance were three times more likely...... to take the (undeserved) maximum payoff than the participants in the random payment scheme. In contrast to previous findings in the cheating literature, stealing is an all-or-nothing decision rather than a trade-off between a slightly higher payoff and the desire to keep ones moral values intact....... The results support the theory that unethical behavior is increased by a sense of entitlement, which is more pronounced when wealth depends on performance than on the roll of a die....

  15. Can increased organic consumption mitigate climate changes?

    DEFF Research Database (Denmark)

    Heerwagen, Lennart Ravn; Andersen, Laura Mørch; Christensen, Tove


    correlation between increasing organic budget shares and decreasing meat budget shares is found. People include food-related behaviour such as the purchase of organic food and reduced meat consumption as ways to mitigate climate change. However, other behavioural modifications such as reduction of car usage...... and household heating are perceived as more important strategies. Research limitations/implications – Other food-related mitigation strategies could be investigated. The climate effect of different diets – and how to motivate consumers to pursue them – could be investigated. Individual as opposed to household...... the climate-friendliness of consumption using consumption of organic food as a case. The authors link stated concerns for climate changes with actual food-related behaviour....

  16. Increased risk for depression after breast cancer

    DEFF Research Database (Denmark)

    Suppli, Nis P; Johansen, Christoffer; Christensen, Jane


    PURPOSE: To investigate the risk for first depression, assessed as incident hospital contacts for depression and incident use of antidepressants, among women with breast cancer. PATIENTS AND METHODS: Danish national registries were used to identify 1,997,669 women with no diagnosis of cancer...... associated with use of antidepressants. CONCLUSION: Women with breast cancer are at long-term increased risk for first depression, including both severe episodes leading to hospital contact and use of antidepressants. Clinicians should be aware that the risk is highest in women with comorbid conditions, node...... or a major psychiatric disorder. This cohort was followed from 1998 to 2011 for a diagnosis of breast cancer and for the two outcomes, hospital contact for depression and redeemed prescriptions for antidepressants. Rate ratios for incident hospital contacts for depression and incident use of antidepressants...

  17. Increased tolerance to humans among disturbed wildlife (United States)

    Samia, Diogo S. M.; Nakagawa, Shinichi; Nomura, Fausto; Rangel, Thiago F.; Blumstein, Daniel T.


    Human disturbance drives the decline of many species, both directly and indirectly. Nonetheless, some species do particularly well around humans. One mechanism that may explain coexistence is the degree to which a species tolerates human disturbance. Here we provide a comprehensive meta-analysis of birds, mammals and lizards to investigate species tolerance of human disturbance and explore the drivers of this tolerance in birds. We find that, overall, disturbed populations of the three major taxa are more tolerant of human disturbance than less disturbed populations. The best predictors of the direction and magnitude of bird tolerance of human disturbance are the type of disturbed area (urbanized birds are more tolerant than rural or suburban populations) and body mass (large birds are more tolerant than small birds). By identifying specific features associated with tolerance, these results guide evidence-based conservation strategies to predict and manage the impacts of increasing human disturbance on birds. PMID:26568451

  18. Higher social class predicts increased unethical behavior. (United States)

    Piff, Paul K; Stancato, Daniel M; Côté, Stéphane; Mendoza-Denton, Rodolfo; Keltner, Dacher


    Seven studies using experimental and naturalistic methods reveal that upper-class individuals behave more unethically than lower-class individuals. In studies 1 and 2, upper-class individuals were more likely to break the law while driving, relative to lower-class individuals. In follow-up laboratory studies, upper-class individuals were more likely to exhibit unethical decision-making tendencies (study 3), take valued goods from others (study 4), lie in a negotiation (study 5), cheat to increase their chances of winning a prize (study 6), and endorse unethical behavior at work (study 7) than were lower-class individuals. Mediator and moderator data demonstrated that upper-class individuals' unethical tendencies are accounted for, in part, by their more favorable attitudes toward greed.

  19. Increasing the discrimination of SAR recognition models (United States)

    Bhanu, Bir; Jones, Grinnell, III


    The focus of this paper is optimizing recognition models for Synthetic Aperture Radar signatures of vehicles to improve the performance of a recognition algorithm under the extended operating conditions of target articulation, occlusion and configuration variants. The recognition models are based on quasi-invariant local features, scattering center locations and magnitudes. The approach determines the similarities and differences among the various vehicle models. Methods to penalize similar features or reward dissimilar features are used to increase the distinguishability of the recognition model instances. Extensive experimental recognition results are presented in terms of confusion matrices and receiver operating characteristic curves to show the improvements in recognition performance for MSTAR vehicle targets with articulation, configuration variants and occlusion.

  20. Increasing the protein content of ice cream. (United States)

    Patel, M R; Baer, R J; Acharya, M R


    Vanilla ice cream was made with a mix composition of 10.5% milk fat, 10.5% milk SNF, 12% beet sugar, and 4% corn syrup solids. None of the batches made contained stabilizer or emulsifier. The control (treatment 1) contained 3.78% protein. Treatments 2 and 5 contained 30% more protein, treatments 3 and 6 contained 60% more protein, and treatments 4 and 7 contained 90% more protein compared with treatment 1 by addition of whey protein concentrate or milk protein concentrate powders, respectively. In all treatments, levels of milk fat, milk SNF, beet sugar, and corn syrup solids were kept constant at 37% total solids. Mix protein content for treatment 1 was 3.78%, treatment 2 was 4.90%, treatment 5 was 4.91%, treatments 3 and 6 were 6.05%, and treatments 4 and 7 were 7.18%. This represented a 29.89, 60.05, 89.95, 29.63, 60.05, and 89.95% increase in protein for treatment 2 through treatment 7 compared with treatment 1, respectively. Milk protein level influenced ice crystal size; with increased protein, the ice crystal size was favorably reduced in treatments 2, 4, and 5 and was similar in treatments 3, 6, and 7 compared with treatment 1. At 1 wk postmanufacture, overall texture acceptance for all treatments was more desirable compared with treatment 1. When evaluating all parameters, treatment 2 with added whey protein concentrate and treatments 5 and 6 with added milk protein concentrate were similar or improved compared with treatment 1. It is possible to produce acceptable ice cream with higher levels of protein.

  1. Direct silanization of zirconia for increased biointegration. (United States)

    Caravaca, Carlos; Shi, Liu; Balvay, Sandra; Rivory, Pascaline; Laurenceau, Emmanuelle; Chevolot, Yann; Hartmann, Daniel; Gremillard, Laurent; Chevalier, Jérôme


    High-performance bioinert ceramics such as zirconia have been used for biomedical devices since the early seventies. In order to promote osseointegration, the historical solution has been to increase the specific surface of the implant through roughness. Nevertheless these treatments on ceramics may create defects at the surface, exposing the material to higher chances of early failure. In zirconia, such treatments may also affect the stability of the surface. More recently, the interest of improving osseointegration of implants has moved the research focus towards the actual chemistry of the surface. Inspired by this, we have adapted the current knowledge and techniques of silica functionalization and applied it to successfully introduce 3-aminopropyldimethylethoxy silane (APDMES) directly on the surface of zirconia (3Y-TZP). We used plasma of oxygen to clean the surface and promote hydroxylation of the surface to increase silane density. The samples were extensively characterized by means of X-ray photoelectron spectroscopy (XPS) and contact angle, mechanically tested and its cytotoxicity was evaluated through cell adhesion and proliferation tests. Additionally, aging was studied to discard negative effects of the treatment on the stability of the tetragonal phase. No adverse effect was found on the mechanical response of treated samples. In addition, plasma-treated samples exhibited an unexpectedly higher resistance to aging. Finally, silane density was 35% lower than the one reported in literature for silica. However cells displayed a qualitatively higher spreading in opposition to the rounder appearance of cells on untreated zirconia. These results lay the foundations for the next generation of zirconia implants with biologically friendlier surfaces.

  2. Thinning increases climatic resilience of red pine (United States)

    Magruder, Matthew; Chhin, Sophan; Palik, Brian; Bradford, John B.


    Forest management techniques such as intermediate stand-tending practices (e.g., thinning) can promote climatic resiliency in forest stands by moderating tree competition. Residual trees gain increased access to environmental resources (i.e., soil moisture, light), which in turn has the potential to buffer trees from stressful climatic conditions. The influences of climate (temperature and precipitation) and forest management (thinning method and intensity) on the productivity of red pine (Pinus resinosa Ait.) in Michigan were examined to assess whether repeated thinning treatments were able to increase climatic resiliency (i.e., maintaining productivity and reduced sensitivity to climatic stress). The cumulative productivity of each thinning treatment was determined, and it was found that thinning from below to a residual basal area of 14 m2·ha−1 produced the largest average tree size but also the second lowest overall biomass per acre. On the other hand, the uncut control and the thinning from above to a residual basal area of 28 m2·ha−1 produced the smallest average tree size but also the greatest overall biomass per acre. Dendrochronological methods were used to quantify sensitivity of annual radial growth to monthly and seasonal climatic factors for each thinning treatment type. Climatic sensitivity was influenced by thinning method (i.e., thinning from below decreased sensitivity to climatic stress more than thinning from above) and by thinning intensity (i.e., more intense thinning led to a lower climatic sensitivity). Overall, thinning from below to a residual basal area of 21 m2·ha−1 represented a potentially beneficial compromise to maximize tree size, biomass per acre, and reduced sensitivity to climatic stress, and, thus, the highest level of climatic resilience.

  3. Increasing the brightness of light sources

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Ling


    In this work the principle of light recycling is applied to artificial light sources in order to achieve brightness enhancement. Firstly, the feasibilities of increasing the brightness of light sources via light recycling are examined theoretically, based on the fundamental laws of thermodynamics including Kirchhoff's law on radiation, Planck's law, Lambert-Beer's law, the etendue conservation and the brightness theorem. From an experimental viewpoint, the radiation properties of three different kinds of light sources including short-arc lamps, incandescent lamps and LEDs characterized by their light-generating mechanisms are investigated. These three types of sources are used in light recycling experiments, for the purpose of 1. validating the intrinsic light recycling effect in light sources, e. g. the intrinsic light recycling effect in incandescent lamps stemming from the coiled filament structure. 2. acquiring the required parameters for establishing physical models, e.g. the emissivity/absorptivity of the short-arc lamps, the intrinsic reflectivity and the external quantum efficiency of LEDs. 3. laying the foundations for designing optics aimed at brightness enhancement according to the characteristics of the sources and applications. Based on the fundamental laws and experiments, two physical models for simulating the radiance distribution of light sources are established, one for thermal filament lamps, the other for luminescent sources, LEDs. As validation of the theoretical and experimental investigation of the light recycling effect, an optical device, the Carambola, is designed for achieving deterministic and multiple light recycling. The Carambola has the function of a concentrator. In order to achieve the maximum possible brightness enhancement with the Carambola, several combinations of sources and Carambolas are modelled in ray-tracing simulations. Sources with different light-emitting mechanisms and different radiation properties

  4. Cryotherapy induces an increase in muscle stiffness. (United States)

    Point, Maxime; Guilhem, Gaël; Hug, François; Nordez, Antoine; Frey, Alain; Lacourpaille, Lilian


    Although cold application (i.e., cryotherapy) may be useful to treat sports injuries and to prevent muscle damage, it is unclear whether it has adverse effects on muscle mechanical properties. This study aimed to determine the effect of air-pulsed cryotherapy on muscle stiffness estimated using ultrasound shear wave elastography. Myoelectrical activity, ankle passive torque, shear modulus (an index of stiffness) and muscle temperature of the gastrocnemius medialis were measured before, during an air-pulsed cryotherapy (-30°) treatment of 4 sets of 4 minutes with 1 min recovery in between, and during a 40-min post-cryotherapy period. Muscle temperature significantly decreased after the second set of treatment (10 min: 32.3 ± 2.5°C; P < 0.001), peaked at 29 min (27.9 ± 2.2°C; P < 0.001) and remained below baseline values at 60 minutes (29.5 ± 2.0°C; P < 0.001). Shear modulus increased by +11.5 ± 11.8% after the second set (10 min; P = 0.011), peaked at 30 min (+34.7 ± 42.6%; P < 0.001) and remained elevated until the end of the post-treatment period (+25.4 ± 17.1%; P < 0.001). These findings provide evidence that cryotherapy induces an increase in muscle stiffness. This acute change in muscle mechanical properties may lower the amount of stretch that the muscle tissue is able to sustain without subsequent injury. This should be considered when using cryotherapy in athletic practice. This article is protected by copyright. All rights reserved.

  5. Aeromonas dhakensis, an increasingly recognized human pathogen

    Directory of Open Access Journals (Sweden)

    Po Lin eChen


    Full Text Available Aeromonas dhakensis was first isolated from children with diarrhea in Dhaka, Bangladesh and described in 2002. In the past decade, increasing evidence indicate this species is widely distributed in the environment and can cause a variety of infections both in human and animals, especially in coastal areas. A. dhakensis is often misidentified as A. hydrophila, A. veronii or A. caviae by commercial phenotypic tests in the clinical laboratory. Correct identification relies on molecular methods. Increasingly used matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS may be able to identify Aeromonas specie rapidly and accurately. A. dhakensis has shown its potent virulence in different animal models and clinical infections. Although several virulence factors had been reported, no single mechanism is conclusive. Characteristically A. dhakensis is the principal species causing soft tissue infection and bacteremia, especially among patients with liver cirrhosis or malignancy. Of note, A. dhakensis bacteremia is more lethal than bacteremia due to other Aeromonas species. The role of this species in gastroenteritis remains controversial. Third generation cephalosporins and carbapenems should be used cautiously in the treatment of severe A. dhakensis infection due to the presence of AmpC β-lactamase and metallo-β-lactamase genes, and optimal regimens may be cefepime or fluoroquinolones. Studies of bacterial virulence factors and associated host responses may provide the chance to understand the heterogeneous virulence between species. The hypothesis A. dhakensis with varied geographic prevalence and enhanced virulence that compared to other Aeromonas species warrants more investigations.

  6. Towards increased visibility of multimorbidity research

    Directory of Open Access Journals (Sweden)

    Aline Ramond-Roquin


    Full Text Available The number of people living with comorbidity, multimorbidity, or multiple chronic conditions, hereafter referred to as “multimorbidity” (see Box 1 [1,2], has become the norm rather than the exception in healthcare. In developed countries, approximately one in four adults have at least two chronic conditions [3,4], and over half of older adults have three or more [5]. Although the prevalence of multimorbidity increases with age, many studies have reported high rates of multimorbidity even among younger adults [6]. Multimorbidity negatively impacts patient outcomes, including physical and psychological functioning, quality of life, and life expectancy [7,8]. It also complicates treatment and increases healthcare utilization and costs [9–11]. Despite representing a large – and growing – proportion of adults seen in primary care today, there is a major gap in our understanding of how best to address, meet, and satisfy the complex care needs of patients with multimorbidity [11]. The traditional single-disease model of care does not work for them, and multimorbidity should definitively not be considered as the simple juxtaposition of independent conditions [12,13]. Fortunately though, interest in multimorbidity is growing worldwide, and has become a healthcare and research priority [14,15]. An international community interested in multimorbidity research has recently emerged and become organized through different activities, such as the creation of the Journal of Comorbidity, a weblog that hosts and supports the exchanges from the International Research Community on Multimorbidity [16], the organization of an international forum [17] at the North American Primary Care Research Group (NAPCRG congress, and the publication of an “ABC of Multimorbidity” [1]. Journal of Comorbidity 2016;6(2:42–45

  7. Plasma alpha(2) macroglobulin is increased in nephrotic patients as a result of increased synthesis alone

    NARCIS (Netherlands)

    Sain-van der Velden, MGM; Rabelink, TJ; Reijngoud, DJ; Gadellaa, MM; Voorbij, HAM; Stellaard, F; Kaysen, GA


    Background. alpha(2) Macroglobulin (alpha(2)M), a protease inhibitor, is often increased in plasma of patients with the nephrotic syndrome. Although it has been speculated that synthesis is increased, no direct measurements have been performed. Methods. alpha(2)M synthesis in both normal subjects (N

  8. Seismological Evidence for Increasing Oceanic Storm Intensity (United States)

    McNamara, D. E.; Aster, R.; Bromirski, P.; Hutt, C.; Gee, L.


    detection and analysis. Inferior instrumentation, inconsistent techniques, and incomplete data can lead to artificial trends and, consequently, to incorrect interpretations. An advantage of our technique is that it is independent of seismic data age, quality and completeness. We measure the change in microseism intensities over time by computing a measure called the microseism index (Grevemeyer et al., 2000) at 14 long operating GSN and precursor stations. The oldest station in our study, HG.ALQ, began operation in 1972 and is a precursor to IU.ANMO in Albuquerque, NM. For the period 1972-2007 we detect clear microseismic signal and demonstrate an increasing trend through time. The positive trend in microseism levels suggests that oceanic wave maximum heights have increased, and correlates with other metrics showing increasing surface sea and air temperatures and oceanic storminess.

  9. Increasing herd immunity with influenza revaccination. (United States)

    Mooring, E Q; Bansal, S


    Seasonal influenza is a significant public health concern globally. While influenza vaccines are the single most effective intervention to reduce influenza morbidity and mortality, there is considerable debate surrounding the merits and consequences of repeated seasonal vaccination. Here, we describe a two-season influenza epidemic contact network model and use it to demonstrate that increasing the level of continuity in vaccination across seasons reduces the burden on public health. We show that revaccination reduces the influenza attack rate not only because it reduces the overall number of susceptible individuals, but also because it better protects highly connected individuals, who would otherwise make a disproportionately large contribution to influenza transmission. We also demonstrate that our results hold on an empirical contact network, in the presence of assortativity in vaccination status, and are robust for a range of vaccine coverage and efficacy levels. Our work contributes a population-level perspective to debates about the merits of repeated influenza vaccination and advocates for public health policy to incorporate individual vaccine histories.

  10. Increasing tsunami risk awareness via mobile application (United States)

    Leelawat, N.; Suppasri, A.; Latcharote, P.; Imamura, F.; Abe, Y.; Sugiyasu, K.


    In the information and communication technology era, smartphones have become a necessity. With the capacity and availability of smart technologies, a number of benefits are possible. As a result, designing a mobile application to increase tsunami awareness has been proposed, and a prototype has been designed and developed. The application uses data from the 2011 Great East Japan Tsunami. Based on the current location determined by a GPS function matched with the nearest point extracted from the detailed mesh data of that earlier disaster, the application generates the inundation depth at the user’s location. Thus, not only local people but also tourists visiting the affected areas can understand the risks involved. Application testing has been conducted in an evacuation experiment involving both Japanese and foreign students. The proposed application can be used as a supplementary information tool in tsunami evacuation drills. It also supports the idea of smart tourism: when people realize their risks, they possess risk awareness and hence can reduce their risks. This application can also be considered a contribution to disaster knowledge and technology, as well as to the lessons learned from the practical outcome.

  11. Increased risk of lymphoma in sicca syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kassan, S.S.; Thomas, T.L.; Moutsopoulos, H.M.; Hoover, R.; Kimberly, R.P.; Budman, D.R.; Costa, J.; Decker, J.L.; Chused, T.M.


    The risk of cancer was ascertained in 136 women with sicca syndrome followed at the National Institutes of Health (NIH). Seven patients developed non-Hodgkin's lymphoma from 6 months to 13 years after their first admission to NIH. This was 43.8 times (P less than 0.01) the incidence expected from the rates of cancer prevailing among women of the same age range in the general population during this time. In addition, three cases of Waldenstroem's macroglobulinemia occurred in this study group. Eight patients developed cancers other than lymphoma, similar to the number expected based on the rates prevailing in the general population. Patients with a history of parotid enlargement, splenomegaly, and lymphadenopathy had an increased risk of lymphoma. These clinical conditions did not appear to be early manifestations of undiagnosed lymphoma but rather seemed to identify a subgroup of patients with sicca syndrome with marked lymphoid reactivity, who had a particularly high risk of subsequently developing lymphoma.

  12. Fertilization increases paddy soil organic carbon density. (United States)

    Wang, Shao-xian; Liang, Xin-qiang; Luo, Qi-xiang; Fan, Fang; Chen, Ying-xu; Li, Zu-zhang; Sun, Huo-xi; Dai, Tian-fang; Wan, Jun-nan; Li, Xiao-jun


    Field experiments provide an opportunity to study the effects of fertilization on soil organic carbon (SOC) sequestration. We sampled soils from a long-term (25 years) paddy experiment in subtropical China. The experiment included eight treatments: (1) check, (2) PK, (3) NP, (4) NK, (5) NPK, (6) 7F:3M (N, P, K inorganic fertilizers+30% organic N), (7) 5F:5M (N, P, K inorganic fertilizers+50% organic N), (8) 3F:7M (N, P, K inorganic fertilizers+70% organic N). Fertilization increased SOC content in the plow layers compared to the non-fertilized check treatment. The SOC density in the top 100 cm of soil ranged from 73.12 to 91.36 Mg/ha. The SOC densities of all fertilizer treatments were greater than that of the check. Those treatments that combined inorganic fertilizers and organic amendments had greater SOC densities than those receiving only inorganic fertilizers. The SOC density was closely correlated to the sum of the soil carbon converted from organic amendments and rice residues. Carbon sequestration in paddy soils could be achieved by balanced and combined fertilization. Fertilization combining both inorganic fertilizers and organic amendments is an effective sustainable practice to sequestrate SOC.

  13. Predicting Increased Blood Pressure Using Machine Learning

    Directory of Open Access Journals (Sweden)

    Hudson Fernandes Golino


    Full Text Available The present study investigates the prediction of increased blood pressure by body mass index (BMI, waist (WC and hip circumference (HC, and waist hip ratio (WHR using a machine learning technique named classification tree. Data were collected from 400 college students (56.3% women from 16 to 63 years old. Fifteen trees were calculated in the training group for each sex, using different numbers and combinations of predictors. The result shows that for women BMI, WC, and WHR are the combination that produces the best prediction, since it has the lowest deviance (87.42, misclassification (.19, and the higher pseudo R2 (.43. This model presented a sensitivity of 80.86% and specificity of 81.22% in the training set and, respectively, 45.65% and 65.15% in the test sample. For men BMI, WC, HC, and WHC showed the best prediction with the lowest deviance (57.25, misclassification (.16, and the higher pseudo R2 (.46. This model had a sensitivity of 72% and specificity of 86.25% in the training set and, respectively, 58.38% and 69.70% in the test set. Finally, the result from the classification tree analysis was compared with traditional logistic regression, indicating that the former outperformed the latter in terms of predictive power.

  14. Increase of Prostate Cancer Incidence in Martinique

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    Dominique Belpomme


    Full Text Available Prostate cancer incidence is steadily increasing in many developed countries. Because insular populations present unique ethnic, geographical, and environmental characteristics, we analyzed the evolution of prostate cancer age-adjusted world standardized incidence rates in Martinique in comparison with that of metropolitan France. We also compared prostate cancer incidence rates, and lifestyle-related and socioeconomic markers such as life expectancy, dietary energy, and fat supply and consumption, with those in other Caribbean islands, France, UK, Sweden, and USA. The incidence rate of prostate cancer in Martinique is one of the highest reported worldwide; it is continuously growing since 1985 in an exponential mode, and despite a similar screening detection process and lifestyle-related behaviour, it is constantly at a higher level than in metropolitan France. However, Caribbean populations that are genetically close to that of Martinique have generally much lower incidence of prostate cancer. We found no correlation between prostate cancer incidence rates, life expectancy, and diet westernization. Since the Caribbean African descent-associated genetic susceptibility factor would have remained constant during the 1980–2005, we suggest that in Martinique some environmental change including the intensive use of carcinogenic organochlorine pesticides might have occurred as key determinant of the persisting highly growing incidence of prostate cancer.

  15. Increased hepcidin expression in colorectal carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Douglas G Ward; Keith Roberts; Matthew J Brookes; Howard Joy; Ashley Martin; Tariq Ismail; Robert Spychal; Tariq Iqbal; Chris Tselepis


    AIM:To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anae-mia and whether it might have a role in colorectal car-cinogenesis.METHODS:Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to measure hepcidin in urine collected from 56 patients with colorectal cancer.Quantitative Real Time RT-PCR was utilised to determine hepcidin mRNA expression in colorectal cancer tissue.Hepcidin cellular localisation was determined using im-munohistochemistry.RESULTS:We demonstrate that whilst urinary hepcidin expression was not correlated with anaemia it was posi-tively associated with increasing T-stage of colorectal cancer (P<0.05).Furthermore,we report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue specimens and was correlated with ferroportin repres-sion.This was supported by hepcidin immunoreactivity in colorectal cancer tissue.CONCLUSION:We demonstrate that systemic hepcidin expression is unlikely to be the cause of the systemic anaemia associated with colorectal cancer.However,we demonstrate for the first time that hepcidin is expressed by colorectal cancer tissue and that this may represent a novel oncogenic signalling mechanism.

  16. Ego depletion increases risk-taking. (United States)

    Fischer, Peter; Kastenmüller, Andreas; Asal, Kathrin


    We investigated how the availability of self-control resources affects risk-taking inclinations and behaviors. We proposed that risk-taking often occurs from suboptimal decision processes and heuristic information processing (e.g., when a smoker suppresses or neglects information about the health risks of smoking). Research revealed that depleted self-regulation resources are associated with reduced intellectual performance and reduced abilities to regulate spontaneous and automatic responses (e.g., control aggressive responses in the face of frustration). The present studies transferred these ideas to the area of risk-taking. We propose that risk-taking is increased when individuals find themselves in a state of reduced cognitive self-control resources (ego-depletion). Four studies supported these ideas. In Study 1, ego-depleted participants reported higher levels of sensation seeking than non-depleted participants. In Study 2, ego-depleted participants showed higher levels of risk-tolerance in critical road traffic situations than non-depleted participants. In Study 3, we ruled out two alternative explanations for these results: neither cognitive load nor feelings of anger mediated the effect of ego-depletion on risk-taking. Finally, Study 4 clarified the underlying psychological process: ego-depleted participants feel more cognitively exhausted than non-depleted participants and thus are more willing to take risks. Discussion focuses on the theoretical and practical implications of these findings.

  17. Touch increases autonomic coupling between romantic partners

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    Jonas eChatel-Goldman


    Full Text Available Interpersonal touch is of paramount importance in human social bonding and close relationships, allowing a unique channel for affect communication. So far the effect of touch on human physiology has been studied at an individual level. The present study aims at extending the study of affective touch from isolated individuals to truly interacting dyads. We have designed an ecological paradigm where romantic partners interact only via touch and we manipulate their empathic states. Simultaneously, we collected their autonomic activity (skin conductance, pulse, respiration. 14 couples participated to the experiment. We found that interpersonal touch increased coupling of electrodermal activity between the interacting partners, regardless the intensity and valence of the emotion felt. In addition, physical touch induced strong and reliable changes in physiological states within individuals. These results support an instrumental role of interpersonal touch for affective support in close relationships. Furthermore, they suggest that touch alone allows the emergence of a somatovisceral resonance between interacting individuals, which in turn is likely to form the prerequisites for emotional contagion and empathy.

  18. Fertilization increases paddy soil organic carbon density

    Institute of Scientific and Technical Information of China (English)

    Shao-xian WANG; Xiao-jun LI; Xin-qiang LIANG; Qi-xiang LUO; Fang FAN; Ying-xu CHEN; Zu-zhang LI; Huo-xi SUN; Tian-fang DAI; Jun-nan WAN


    Field experiments provide an opportunity to study the effects of fertilization on soil organic carbon (SOC)sequestration.We sampled soils from a long-term (25 years) paddy experiment in subtropical China.The experiment included eight treatments:(1) check,(2) PK,(3) NP,(4) NK,(5) NPK,(6) 7F:3M (N,P,K inorganic fertilizers+30% organic N),(7) 5F:5M (N,P,K inorganic fertilizers+50% organic N),(8) 3F:7M (N,P,K inorganic fertilizers+70% organic N).Fertilization increased SOC content in the plow layers compared to the non-fertilized check treatment.The SOC density in the top 100 cm of soil ranged from 73.12 to 91.36 Mg/ha.The SOC densities of all fertilizer treatments were greater than that of the check.Those treatments that combined inorganic fertilizers and organic amendments had greater SOC densities than those receiving only inorganic fertilizers.The SOC density was closely correlated to the sum of the soil carbon converted from organic amendments and rice residues.Carbon sequestration in paddy soils could be achieved by balanced and combined fertilization.Fertilization combining both inorganic fertilizers and organic amendments is an effective sustainable practice to sequestrate SOC.

  19. Increasing trend in retained rectal foreign bodies (United States)

    Ayantunde, Abraham A; Unluer, Zynep


    AIM To highlight the rising trend in hospital presentation of foreign bodies retained in the rectum over a 5-year period. METHODS Retrospective review of the cases of retained rectal foreign bodies between 2008 and 2012 was performed. Patients’ clinical data and yearly case presentation with data relating to hospital episodes were collected. Data analysis was by SPSS Inc. Chicago, IL, United States. RESULTS Twenty-five patients presented over a 5-year period with a mean age of 39 (17-62) years and M: F ratio of 2:1. A progressive rise in cases was noted from 2008 to 2012 with 3, 4, 4, 6, 8 recorded patients per year respectively. The majority of the impacted rectal objects were used for self-/partner-eroticism. The commonest retained foreign bodies were sex vibrators and dildos. Ninty-six percent of the patients required extraction while one passed spontaneously. Two and three patients had retrieval in the Emergency Department and on the ward respectively while 19 patients needed examination under anaesthesia for extraction. The mean hospital stay was 19 (2-38) h. Associated psychosocial issues included depression, deliberate self-harm, illicit drug abuse, anxiety and alcoholism. There were no psychosocial problems identified in 15 patients. CONCLUSION There is a progressive rise in hospital presentation of impacted rectal foreign bodies with increasing use of different objects for sexual arousal. PMID:27830039

  20. Engineering Rhodosporidium toruloides for increased lipid production. (United States)

    Zhang, Shuyan; Skerker, Jeffrey M; Rutter, Charles D; Maurer, Matthew J; Arkin, Adam P; Rao, Christopher V


    Oleaginous yeast are promising organisms for the production of lipid-based chemicals and fuels from simple sugars. In this work, we explored Rhodosporidium toruloides for the production of lipid-based products. This oleaginous yeast natively produces lipids at high titers and can grow on glucose and xylose. As a first step, we sequenced the genomes of two strains, IFO0880, and IFO0559, and generated draft assemblies and annotations. We then used this information to engineer two R. toruloides strains for increased lipid production by over-expressing the native acetyl-CoA carboxylase and diacylglycerol acyltransferase genes using Agrobacterium tumefaciens mediated transformation. Our best strain, derived from IFO0880, was able to produce 16.4 ± 1.1 g/L lipid from 70 g/L glucose and 9.5 ± 1.3 g/L lipid from 70 g/L xylose in shake-flask experiments. This work represents one of the first examples of metabolic engineering in R. toruloides and establishes this yeast as a new platform for production of fatty-acid derived products.

  1. Increasing granular flow rate with obstructions

    Directory of Open Access Journals (Sweden)

    Alan Murray


    Full Text Available We describe a simple experiment involving spheres rolling down an inclined plane towards a bottleneck and through a gap. Results of the experiment indicate that flow rate can be increased by placing an obstruction at optimal positions near the bottleneck. We use the experiment to develop a computer simulation using the PhysX physics engine. Simulations confirm the experimental results and we state several considerations necessary to obtain a model that agrees well with experiment. We demonstrate that the model exhibits clogging, intermittent and continuous flow, and that it can be used as a tool for further investigations in granular flow. Received: 22 November 2015, Accepted: 19 February 2016; Edited by: L. A. Pugnaloni; Reviewed by: C. M. Carlevaro, Instituto de Física de Líquidos y Sistemas Biológicos, La Plata, Argentina; DOI: Cite as: A Murray, F Alonso-Marroquin, Papers in Physics 8, 080003 (2016

  2. Hyperglycemia Increases Susceptibility to Ischemic Necrosis

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    D. Lévigne


    Full Text Available Diabetic patients are at risk for spontaneous foot ulcers, chronic wounds, infections, and tissue necrosis. Current theories suggest that the development and progression of diabetic foot ulcers are mainly caused by arteriosclerosis and peripheral neuropathy. Tissue necrosis plays a primordial role in the progression of diabetic foot ulcers but the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of hyperglycemia per se on the susceptibility of ischemic tissue to necrosis, using a critical ischemic hind limb animal model. We inflicted the same degree of ischemia in both euglycemic and streptozotocin-induced hyperglycemic rats by resecting the external iliac, the femoral, and the saphenous arteries. Postoperative laser Doppler flowmetry of the ischemic feet showed the same degree of reduction in skin perfusion in both hyperglycemic and euglycemic animals. Nevertheless, we found a significantly higher rate of limb necrosis in hyperglycemic rats compared to euglycemic rats (71% versus 29%, resp.. In this study, we revealed that hyperglycemia per se increases the susceptibility to limb necrosis in ischemic conditions. Our results may help to better understand the physiopathology of progressive diabetic wounds and underline the importance of strict glycemic control in patients with critical limb ischemia.

  3. Whey cheese: membrane technology to increase yields. (United States)

    Riera, Francisco; González, Pablo; Muro, Claudia


    Sweet cheese whey has been used to obtain whey cheese without the addition of milk. Pre-treated whey was concentrated by nanofiltration (NF) at different concentration ratios (2, 2.5 and 2.8) or by reverse osmosis (RO) (2-3 times). After the concentration, whey was acidified with lactic acid until a final pH of 4.6-4.8, and heated to temperatures between 85 and 90 °C. The coagulated fraction (supernatant) was collected and freely drained over 4 h. The cheese-whey yield and protein, fat, lactose and ash recoveries in the final product were calculated. The membrane pre-concentration step caused an increase in the whey-cheese yield. The final composition of products was compared with traditional cheese-whey manufacture products (without membrane concentration). Final cheese yields found were to be between 5 and 19.6%, which are higher than those achieved using the traditional 'Requesón' process.

  4. Increased Nuchal Translucency and Pregnancy Outcome

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    A Tahmasebpour


    Full Text Available Background: To study the outcome of cases with nuchal translucency (NT ≥ 95th centile in the first trimester of pregnancy.Methods: This cross sectional study was performed at Iranian Fetal Medicine Foundation (FMF between January 2009 and December 2011. Totally, 186 cases with NT≥ 95th centile who attended for the first trimester screening were studied. All cases with increased NT including those with normal karyotype were followed up with anomaly scan at 18-22 weeks and fetal echocardiography at 22-24 weeks. Pregnancy outcome was extracted from delivery records and pediatrics notes and telephone interviews.Results: Of screened cases, 186 fetuses had an NT≥95th centile, of them 19.8% were abnormal karyotype, including 29 cases of trisomy 21, three of trisomy 18, two of trisomy 13, three of Turner syndrome. 77.8% did not show any abnormalities on follow-up examinations. 4.6% of cases were found to have malformation antenatally and 4% cases postnatally. 11.4% women elected termination of pregnancy without further follow up. There were 4.6% fetal loss and 1.3% hydrops fetalis.Conclusion: In this unselected population, the study showed one out of four fetuses with enlarged NT had an adverse pregnancy outcome (miscarriage, fetal loss, and fetal abnormalities, however the chance of having a normal child after exclusion of chromosomal abnormalities and adverse pregnancy outcome was 95%.

  5. Predicting Increased Blood Pressure Using Machine Learning (United States)

    Golino, Hudson Fernandes; Amaral, Liliany Souza de Brito; Duarte, Stenio Fernando Pimentel; Soares, Telma de Jesus; dos Reis, Luciana Araujo


    The present study investigates the prediction of increased blood pressure by body mass index (BMI), waist (WC) and hip circumference (HC), and waist hip ratio (WHR) using a machine learning technique named classification tree. Data were collected from 400 college students (56.3% women) from 16 to 63 years old. Fifteen trees were calculated in the training group for each sex, using different numbers and combinations of predictors. The result shows that for women BMI, WC, and WHR are the combination that produces the best prediction, since it has the lowest deviance (87.42), misclassification (.19), and the higher pseudo R2 (.43). This model presented a sensitivity of 80.86% and specificity of 81.22% in the training set and, respectively, 45.65% and 65.15% in the test sample. For men BMI, WC, HC, and WHC showed the best prediction with the lowest deviance (57.25), misclassification (.16), and the higher pseudo R2 (.46). This model had a sensitivity of 72% and specificity of 86.25% in the training set and, respectively, 58.38% and 69.70% in the test set. Finally, the result from the classification tree analysis was compared with traditional logistic regression, indicating that the former outperformed the latter in terms of predictive power. PMID:24669313

  6. Increases in rewards promote flexible behavior. (United States)

    Shen, Y Jeremy; Chun, Marvin M


    Offering reward for performance can motivate people to perform a task better, but better preparation for one task usually means decreased flexibility to perform different tasks. In six experiments in which reward varied between low and high levels, we found that reward can encourage people to prepare more flexibly for different tasks, but only as it increased from the level on the previous trial. When the same high rewards were offered continuously trial after trial, people were more inclined to simply stick with doing what had worked previously. We demonstrated such enhancements in flexibility in task switching, a difficult visual search task, and an easier priming of pop-out search task, which shows that this effect generalizes from executive tasks to perceptual processes that require relatively little executive control. These findings suggest that relative, transient changes in reward can exert more potent effects on behavioral flexibility than can the absolute amount of reward, whether it consists of money or points in a social competition.

  7. Voluntary self-touch increases body ownership

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    Masayuki eHara


    Full Text Available Experimental manipulations of body ownership have indicated that multisensory integration is central to forming bodily self-representation. Voluntary self-touch is a unique multisensory situation involving corresponding motor, tactile and proprioceptive signals. Yet, even though self-touch is frequent in everyday life, its contribution to the formation of body ownership is not well understood. Here we investigated the role of voluntary self-touch in body ownership using a novel adaptation of the rubber hand illusion (RHI, in which a robotic system and virtual reality allowed participants self-touch of real and virtual hands. In the first experiment, active and passive self-touch were applied in the absence of visual feedback. In the second experiment, we tested the role of visual feedback in this bodily illusion. Finally, in the third experiment, we compared active and passive self-touch to the classical RHI in which the touch is administered by the experimenter. We hypothesized that active self-touch would increase ownership over the virtual hand through the addition of motor signals strengthening the bodily illusion. The results indicated that active self-touch elicited stronger illusory ownership compared to passive self-touch and sensory only stimulation, and indicate an important role of active self-touch in the formation of bodily self.

  8. Vertical barriers with increased sorption capacities

    Energy Technology Data Exchange (ETDEWEB)

    Bradl, H.B. [Bilfinger + Berger Bauaktiengesellschaft, Mannheim (Germany)


    Vertical barriers are commonly used for the containment of contaminated areas. Due to the very small permeability of the barrier material which is usually in the order of magnitude of 10-10 m/s or less the advective contaminant transport can be more or less neglected. Nevertheless, there will always be a diffusive contaminant transport through the barrier which is caused by the concentration gradient. Investigations have been made to increase the sorption capacity of the barrier material by adding substances such as organoclays, zeolites, inorganic oxides and fly ashes. The contaminants taken into account where heavy metals (Pb) and for organic contaminants Toluole and Phenantrene. The paper presents results of model calculations and experiments. As a result, barrier materials can be designed {open_quotes}tailor-made{close_quotes} depending on the individual contaminant range of each site (e.g. landfills, gasworks etc.). The parameters relevant for construction such as rheological properties, compressive strength and permeability are not affected by the addition of the sorbents.

  9. Increased risk of cancer among azoospermic men (United States)

    Eisenberg, Michael L.; Betts, Paul; Herder, Danielle; Lamb, Dolores J.; Lipshultz, Larry I.


    Objective To determine if men with azoospermia are at an elevated risk of developing cancer in the years following an infertility evaluation. Design Cohort Study Setting United States andrology clinic Patients 2,238 men with complete records were evaluated for infertility at a single andrology clinic in Texas from 1989 to 2009. Interventions None Main Outcome Measures Cancer incidence was determined by linkage to the Texas Cancer Registry. Results In all, 451 men had azoospermia and 1,787 were not azoospermic with a mean age at infertility evaluation of 35.7 years. Compared to the general population, infertile men had a higher risk of cancer with 29 cases observed compared with 16.7 expected (SIR 1.7, 95% CI 1.2–2.5). When stratifying by azoospermia status, azoospermic men had an elevated risk of cancer (SIR 2.9, 95% CI 1.4–5.4). Infertile men without azoospermia had a trend towards a higher rate of cancer (SIR 1.4, 95% CI 0.9–2.2). The Cox regression model revealed that azoospermic men had 2.2-fold higher cancer risk compared to not azoospermic men (HR 2.2, 95% CI 1.0–4.8). Conclusions Men with azoospermia have an increased risk of subsequently developing cancer, suggesting a possible common etiology between azoospermia and cancer development. Additional follow-up of azoospermic men after reproductive efforts end may be warranted. PMID:23790640

  10. Immorally obtained principal increases investors’ risk preference (United States)

    Chen, Jiaxin; He, Guibing


    Capital derived from immoral sources is increasingly circulated in today’s financial markets. The moral associations of capital are important, although their impact on investment remains unknown. This research aims to explore the influence of principal source morality on investors’ risk preferences. Three studies were conducted in this regard. Study 1 finds that investors are more risk-seeking when their principal is earned immorally (through lying), whereas their risk preferences do not change when they invest money earned from neutral sources after engaging in immoral behavior. Study 2 reveals that guilt fully mediates the relationship between principal source morality and investors’ risk preferences. Studies 3a and 3b introduce a new immoral principal source and a new manipulation method to improve external validity. Guilt is shown to the decrease the subjective value of morally flawed principal, leading to higher risk preference. The findings show the influence of morality-related features of principal on people’s investment behavior and further support mental account theory. The results also predict the potential threats of “grey principal” to market stability. PMID:28369117

  11. Social Media Marketing to Increase Brand Awareness

    Directory of Open Access Journals (Sweden)

    Monica Bîja


    Full Text Available Social networks are becoming more and more widespread and they are literally conquering the World Wide Web. Facebook has managed to arrive even in poor and remote territories which apparently have nothing to do with our always on the move modern world. However, only on the African continent there are more than 100 million active Facebook users who represent 50% of the African population having access to Internet. Thus, it would be huge marketing mistake for businesses not to take into consideration this opportunity to get in touch with prospective customers (Neti, 2011. Social media is hot and has turned into a “must” for businesses looking for brand awareness. Therefore, the techniques used to attract customers by means of social networks have gained quite a high degree of sophistry (Neti, 2011. In an age in which the average internet user accesses his/her social network account at least fourteen times a day, companies cannot afford to be absent from this medium. The aim of the present paper is to present the concept and characteristics of social media and how it can be used in order to increase brand awareness.

  12. Does resolution really increase image quality? (United States)

    Tisse, Christel-Loïc; Guichard, Frédéric; Cao, Frédéric


    A general trend in the CMOS image sensor market is for increasing resolution (by having a larger number of pixels) while keeping a small form factor by shrinking photosite size. This article discusses the impact of this trend on some of the main attributes of image quality. The first example is image sharpness. A smaller pitch theoretically allows a larger limiting resolution which is derived from the Modulation Transfer Function (MTF). But recent sensor technologies (1.75μm, and soon 1.45μm) with typical aperture f/2.8 are clearly reaching the size of the diffraction blur spot. A second example is the impact on pixel light sensitivity and image sensor noise. For photonic noise, the Signal-to-Noise-Ratio (SNR) is typically a decreasing function of the resolution. To evaluate whether shrinking pixel size could be beneficial to the image quality, the tradeoff between spatial resolution and light sensitivity is examined by comparing the image information capacity of sensors with varying pixel size. A theoretical analysis that takes into consideration measured and predictive models of pixel performance degradation and improvement associated with CMOS imager technology scaling, is presented. This analysis is completed by a benchmarking of recent commercial sensors with different pixel technologies.

  13. Backcrossing to increase meiotic stability in triticale. (United States)

    Giacomin, R M; Assis, R; Brammer, S P; Nascimento Junior, A; Da-Silva, P R


    Triticale (X Triticosecale Wittmack) is an intergeneric hybrid derived from a cross between wheat and rye. As a newly created allopolyploid, the plant shows instabilities during the meiotic process, which may result in the loss of fertility. This genomic instability has hindered the success of triticale-breeding programs. Therefore, strategies should be developed to obtain stable triticale lines for use in breeding. In some species, backcrossing has been effective in increasing the meiotic stability of lineages. To assess whether backcrossing has the same effect in triticale, indices of meiotic abnormalities, meiotic index, and pollen viability were determined in genotypes from multiple generations of triticale (P1, P2, F1, F2, BC1a, and BC1b). All analyzed genotypes exhibited instability during meiosis, and their meiotic index values were all lower than normal. However, the backcrosses BC1a and BC1b showed the lowest mean meiotic abnormalities and the highest meiotic indices, demonstrating higher stability. All genotypes showed a high rate of pollen viability, with the backcrosses BC1a and BC1b again exhibiting the best values. Statistical analyses confirmed that backcrossing positively affects the meiotic stability of triticale. Our results show that backcrossing should be considered by breeders aiming to obtain triticale lines with improved genomic stability.

  14. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity. (United States)

    Simopoulos, Artemis P


    In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.

  15. Increased Akt signaling in the mosquito fat body increases adult survivorship. (United States)

    Arik, Anam J; Hun, Lewis V; Quicke, Kendra; Piatt, Michael; Ziegler, Rolf; Scaraffia, Patricia Y; Badgandi, Hemant; Riehle, Michael A


    Akt signaling regulates diverse physiologies in a wide range of organisms. We examine the impact of increased Akt signaling in the fat body of 2 mosquito species, the Asian malaria mosquito Anopheles stephensi and the yellow fever mosquito Aedes aegypti. Overexpression of a myristoylated and active form of A. stephensi and Ae. aegypti Akt in the fat body of transgenic mosquitoes led to activation of the downstream signaling molecules forkhead box O (FOXO) and p70 S6 kinase in a tissue and blood meal-specific manner. In both species, increased Akt signaling in the fat body after blood feeding significantly increased adult survivorship relative to nontransgenic sibling controls. In A. stephensi, survivorship was increased by 15% to 45%, while in Ae. aegypti, it increased 14% to 47%. Transgenic mosquitoes fed only sugar, and thus not expressing active Akt, had no significant difference in survivorship relative to nontransgenic siblings. Expression of active Akt also increased expression of fat body vitellogenin, but the number of viable eggs did not differ significantly between transgenic and nontransgenic controls. This work demonstrates a novel mechanism of enhanced survivorship through increased Akt signaling in the fat bodies of multiple mosquito genera and provides new tools to unlock the molecular underpinnings of aging in eukaryotic organisms.

  16. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

    Directory of Open Access Journals (Sweden)

    Artemis P. Simopoulos


    Full Text Available In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.

  17. Increased apoptosis of lactotrophs in streptozotocin-induced diabetic rats is followed by increased proliferation. (United States)

    Arroba, Ana I; Lechuga-Sancho, Alfonso M; Frago, Laura M; Argente, Jesús; Chowen, Julie A


    Poorly controlled diabetes mellitus can result in decreased prolactin production and thus problems with lactation, reproduction, and other physiological processes. This may be due to a loss of lactotrophs, as we have previously shown that long-term (8 weeks) poorly controlled streptozotocin-induced diabetes results in increased death of lactotrophs and that this most likely occurs through the activation of caspase-8 and the extrinsic cell death cascade. However, cell proliferation is also increased in the anterior pituitary at this time, although the cell type undergoing this proliferation and whether it is a response to the increased cell death remains unknown. In order to determine the time-course of increased cell death and proliferation in the anterior pituitary and if this is related to changes in tumor necrosis factor (TNF)-alpha, a cytokine involved in the activation of the extrinsic cell death pathway, rats were killed at 1, 4, 6, and 8 weeks after the induction of diabetes. Cell death was significantly increased after 4 weeks, as was caspase-8 activation, although circulating levels of TNF-alpha were increased as early as 1 week. Pituitary levels of TNF-alpha did not change significantly until 8 weeks after diabetes onset. Similarly, Western-blot analysis of proliferating cell nuclear antigen showed that anterior pituitary cell proliferation increased significantly 8 weeks after diabetes onset, with the majority of proliferating cells, as detected by BrdU incorporation, corresponding to lactotrophs. These results suggest that the increased death of lactotrophs in poorly controlled diabetic rats is followed by increased proliferation of this cell type, even when no treatment is given.

  18. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity


    Artemis P. Simopoulos


    In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have sugg...

  19. Tremendously increased lifetime of MCP-PMTs (United States)

    Lehmann, A.; Britting, A.; Eyrich, W.; Pfaffinger, M.; Uhlig, F.; Belias, A.; Dzhygadlo, R.; Gerhardt, A.; Götzen, K.; Kalicy, G.; Krebs, M.; Lehmann, D.; Nerling, F.; Patsyuk, M.; Peters, K.; Schepers, G.; Schmitt, L.; Schwarz, C.; Schwiening, J.; Traxler, M.; Zühlsdorf, M.; Düren, M.; Etzelmüller, E.; Föhl, K.; Hayrapetyan, A.; Kröck, B.; Merle, O.; Rieke, J.; Schmidt, M.; Cowie, E.; Keri, T.; Achenbach, P.; Cardinali, M.; Hoek, M.; Lauth, W.; Schlimme, S.; Sfienti, C.; Thiel, M.


    Microchannel plate (MCP) PMTs are very attractive photon sensors for low light level applications in strong magnetic fields. However, until recently the main drawback of MCP-PMTs was their aging behavior which manifests itself in a limited lifetime due to a rapidly decreasing quantum efficiency (QE) of the photo cathode (PC) as the integrated anode charge (IAC) increases. In the latest models of PHOTONIS, Hamamatsu, and BINP novel techniques are applied to avoid these aging effects which are supposed to be mainly caused by feedback ion impinging on the PC and damaging it. For more than four years we are running a long-term aging test with new lifetime-enhanced MCP-PMT models by simultaneously illuminating various PMTs with roughly the same photon rate. This allows a fair comparison of the lifetime of all investigated MCP-PMTs and will give some insight into the best techniques to be applied for a lifetime enhancement. In this paper the results of comprehensive aging tests will be discussed. Gain, dark count rate and QE were investigated for their dependence on the IAC. The QE was measured spectrally resolved and as a function of the position across the PC to identify regions where the damage develops first. For the best performing tubes the lifetime improvement compared to former MCP-PMTs is a factor of ∼ 50 based on an IAC of meanwhile > 10 C /cm2. This breakthrough in the lifetime of MCP-PMTs was achieved by coating the MCP pores with an atomic layer deposition (ALD) technique.

  20. Increasing numbers of migrants challenge policymakers worldwide. (United States)

    Martin, P


    International migration has increased greatly in the 1990s. In the mid-1990s there were about 125 million migrants (about 2% of the world's population) not living in their country of birth or citizenship. There are 2-4 million new migrants each year. The global migrant population is concentrated in only a few countries. In many Middle Eastern countries, foreign workers make up most of the labor force (60-90%). Africa and western Asia have more than 50% of all 27 million refugees and displaced persons. Germany, France, the UK, the US, Italy, Japan, and Canada have about 33% of the migrant population. Newly arriving immigrants make up a large percentage of annual population growth in industrialized countries with low birth rates (100% in Germany and about 33% in the US). Major migration flows are from Mexico, Central America, and Asia to the US; from North Africa and eastern Europe to western Europe; and from the Philippines and India to the Middle East. Two US legalization programs contributed to a resurgence in immigration in the early 1990s. Many of the world's top economic powers are very concerned about immigration. Economic growth can cut down on economic migration. Many specialists think that freer trade, more foreign investment, and, in some cases, aid can spark economic growth. Many residents of countries receiving migrants want immigration curtailed. Many industrial democracies handle difficult migration issues by making trade-offs, particularly combine stricter immigration controls with more assistance to integrate new immigrants and liberalize trade so countries can export goods instead of people.

  1. The myokine irisin increases cortical bone mass (United States)

    Colaianni, Graziana; Cuscito, Concetta; Mongelli, Teresa; Pignataro, Paolo; Buccoliero, Cinzia; Liu, Peng; Lu, Ping; Sartini, Loris; Di Comite, Mariasevera; Mori, Giorgio; Di Benedetto, Adriana; Brunetti, Giacomina; Yuen, Tony; Sun, Li; Reseland, Janne E.; Colucci, Silvia; New, Maria I.; Zaidi, Mone; Cinti, Saverio; Grano, Maria


    It is unclear how physical activity stimulates new bone synthesis. We explored whether irisin, a newly discovered myokine released upon physical activity, displays anabolic actions on the skeleton. Young male mice were injected with vehicle or recombinant irisin (r-irisin) at a low cumulative weekly dose of 100 µg kg−1. We observed significant increases in cortical bone mass and strength, notably in cortical tissue mineral density, periosteal circumference, polar moment of inertia, and bending strength. This anabolic action was mediated primarily through the stimulation of bone formation, but with parallel notable reductions in osteoclast numbers. The trabecular compartment of the same bones was spared, as were vertebrae from the same mice. Higher irisin doses (3,500 µg kg−1 per week) cause browning of adipose tissue; this was not seen with low-dose r-irisin. Expectedly, low-dose r-irisin modulated the skeletal genes, Opn and Sost, but not Ucp1 or Pparγ expression in white adipose tissue. In bone marrow stromal cell cultures, r-irisin rapidly phosphorylated Erk, and up-regulated Atf4, Runx2, Osx, Lrp5, β-catenin, Alp, and Col1a1; this is consistent with a direct receptor-mediated action to stimulate osteogenesis. We also noted that, although the irisin precursor Fndc5 was expressed abundantly in skeletal muscle, other sites, such as bone and brain, also expressed Fndc5, albeit at low levels. Furthermore, muscle fibers from r-irisin–injected mice displayed enhanced Fndc5 positivity, and irisin induced Fdnc5 mRNA expression in cultured myoblasts. Our data therefore highlight a previously unknown action of the myokine irisin, which may be the molecular entity responsible for muscle–bone connectivity. PMID:26374841

  2. Does Ramadan Fasting Increase duodenal ulcer perforation?

    Directory of Open Access Journals (Sweden)

    Abdoulhossein Davoodabadi


    Full Text Available Introduction: In Ramadan, healthy adult Muslims are obliged to fast. Prolonged fasting increase gastric acid and pepsin levels, which promote the risk of duodenal ulcer perforation (DUP. Effects of Ramadan fasting on DUP have not been thoroughly studied yet, and the limited number of studies investigating the impact of Ramadan fasting on DUP yielded discrepant results. This study aimed to evaluate DUP frequency during Ramadan 2011-2015 and compare it with other months. Methods: This cross-sectional study was performed in 82 patients undergoing surgery due to DUP during July 2011-September 2015. The demographics, history of addiction, use of nonsteroidal and antiinflammatory drugs, previous history of acid peptic disease, as well as complications and outcomes of treatment were recorded and analyzed, and the obtained results were compared between Ramadan and other lunar months. Results: The majority of patients were male (86.6%, 71 patients, with a mean age of 43.9±16.5 years (age range: 20-75 years. Male to female ratio was 6:1. Cases with less than 30 years of age were less frequent (22%, 18 patients. DUP was more frequent during Rajab with nine cases (11%, while during Ramadan, six cases were reported, the difference between Ramadan and other months regarding the incidence of DUP was not significant (P=0.7. Risk factors such as smoking (60% and addiction (44%; especially to crystal and crack were noted. Consumption of nonsteroidal antiinflammatory drugs in 20 (24% patients, and use of antacids in 17 (25% patients. Distribution of DUP in different blood types was as follows: O+=41%, A+=28%, B+=23%, AB=5%, and O-=3%; moreover, post-operative Helicobacter pylori antibody was present in 67% of the patients. Conclusion: Ramadan fasting did not escalate DUP incidence, and those with DUP risk factors can fast with the use of antacids.

  3. Policy challenges of increasing automation in driving

    Directory of Open Access Journals (Sweden)

    Ata M. Khan


    Full Text Available The convergence of information and communication technologies (ICT with automotive technologies has already resulted in automation features in road vehicles and this trend is expected to continue in the future owing to consumer demand, dropping costs of components, and improved reliability. While the automation features that have taken place so far are mainly in the form of information and driver warning technologies (classified as level I pre-2010, future developments in the medium term (level II 2010–2025 are expected to exhibit connected cognitive vehicle features and encompass increasing degree of automation in the form of advanced driver assistance systems. Although autonomous vehicles have been developed for research purposes and are being tested in controlled driving missions, the autonomous driving case is only a long term (level III 2025+ scenario. This paper contributes knowledge on technological forecasts regarding automation, policy challenges for each level of technology development and application context, and the essential instrument of cost-effectiveness for policy analysis which enables policy decisions on the automation systems to be assessed in a consistent and balanced manner. The cost of a system per vehicle is viewed against its effectiveness in meeting policy objectives of improving safety, efficiency, mobility, convenience and reducing environmental effects. Example applications are provided that illustrate the contribution of the methodology in providing information for supporting policy decisions. Given the uncertainties in system costs as well as effectiveness, the tool for assessing policies for future generation features probabilistic and utility-theoretic analysis capability. The policy issues defined and the assessment framework enable the resolution of policy challenges while allowing worthy innovative automation in driving to enhance future road transportation.

  4. Human preference and acceptance of increased air velocity to offset warm sensation at increased room temperatures

    DEFF Research Database (Denmark)

    Cattarin, Giulio; Simone, Angela; Olesen, Bjarne W.

    . The present climatic chamber study examined energy performance and achievable thermal comfort of traditional and bladeless desk fans. Different effects of mechanical and simulated-natural airflow patterns were also investigated. 32 Scandinavians, performing office activities and wearing light clothes , were......Previous studies have demonstrated that in summertime increased air velocities can compensate for higher room temperatures to achieve comfortable conditions. In order to increase air movement, windows opening, ceiling or desk fans can be used at the expense of relatively low energy consumption...... exposed to a increased air movement generated by a personal desk fan. The subjects could continuously regulate the fans under three fixed environmental conditions (operative temperatures equal to 26 °C, 28 °C, or 30 °C, and same absolute humidity 12.2 g/m3). The experimental study showed that increased...

  5. Increased Soft Drink Consumption is Contributing to an Increased Incidence of Obesity


    Yule, Amy


    Regular, non-diet, soft drinks are responsible for one third of the excessive amount of added sweeteners in the diets of children and adolescents (5). Children and adolescents who drink regular soft drinks have a higher caloric intake than those who not drink regular soft drinks (3). Furthermore, BMI and the frequency of obesity were found to increase for each additional serving of sugar sweetened drink consumed by children (10 to 12 years) (6). The increased level of sweetener in regular sof...

  6. Increasing dietary crude protein does not increase the methionine requirement in kittens. (United States)

    Strieker, M J; Morris, J G; Kass, P H; Rogers, Q R


    The objective of this study was to determine if the methionine (met) requirement of kittens is correlated with the concentration of dietary crude protein (CP). The study used 48 male kittens in two replications of six 4 x 4 Latin squares, each representing one concentration of met (1.5, 2.5, 3.5, 4.5, 6.0 or 9.0 g/kg diet) with four CP concentrations (150, 200, 300 and 500 g/kg diet) in 2-week periods. Cystine was present in the lowest CP diet at 5.3 g/kg diet and increased as dietary CP increased. Body weight gain, food intake, nitrogen balance and plasma amino acids, glucose, insulin, cortisol, somatomedin C, T(3) and T(4) concentrations on day 12 were measured. From breakpoint analysis of the nitrogen retention curves, the met requirement of kittens was found to be 3.1, 3.8, 3.1 and 2.4 g met/kg for the 150, 200, 300 and 500 g CP/kg diets, respectively. When met was limiting (1.5 or 2.5 g/kg diet), increasing dietary CP did not decrease, but rather increased food intake, body weight gain and nitrogen retention. Plasma met concentrations increased as dietary met increased and at 2.5-3.5 g met/kg diet were not different among kittens fed the various CP diets. Total plasma T(3) and T(4) increased significantly as dietary CP increased in kittens given the 2.5 and 4.5 g met/kg diets. Results indicate that food intake and possibly altered hormonal secretion play a role in this growth response. In conclusion, the met requirement of growing kittens, unlike omnivores and herbivores studied, was not positively correlated with the concentration of dietary CP.

  7. Estradiol increases the anorexia associated with increased 5-HT(2C) receptor activation in ovariectomized rats. (United States)

    Rivera, Heidi M; Santollo, Jessica; Nikonova, Larissa V; Eckel, Lisa A


    Estradiol's inhibitory effect on food intake is mediated, in part, by its ability to increase the activity of meal-related signals, including serotonin (5-HT), which hastens satiation. The important role that postsynaptic 5-HT(2C) receptors play in mediating 5-HT's anorexigenic effect prompted us to investigate whether a regimen of acute estradiol treatment increases the anorexia associated with increased 5-HT(2C) receptor activation in ovariectomized (OVX) rats. We demonstrated that intraperitoneal and intracerebroventricular (i.c.v.) administration of low doses of the 5-HT(2C) receptor agonist meta-chlorophenylpiperazine (mCPP) decreased 1-h dark-phase food intake in estradiol-treated, but not oil-treated, OVX rats. During a longer feeding test, we demonstrated that i.c.v. administration of mCPP decreased 22-h food intake in oil-treated and, to a greater extent, estradiol-treated OVX rats. In a second study, we demonstrated that estradiol increased 5-HT(2C) receptor protein content in the caudal brainstem, but not hypothalamus, of OVX rats. We conclude that a physiologically-relevant regimen of acute estradiol treatment increases sensitivity to mCPP's anorexigenic effect. Our demonstration that this same regimen of estradiol treatment increases 5-HT(2C) receptor protein content in the caudal hindbrain of OVX rats provides a possible mechanism to explain our behavioral findings.

  8. Eosinophils increase in animals that received biotherapic

    Directory of Open Access Journals (Sweden)

    Pedro Gilberto Silva Morais


    morphological changes in juveniles and adults ticks parasitizing animals which consumed the biotherapic. This observation suggests a negative interference of the biotherapic in the biological cycle of the tick, decreasing its population and consequently his control’s necessity. Comparing the blood cells counts of the first and the twelfth month, a raise of 23% (P> 0.05 in the eosinophils and 8% (P< 0.05 in the platelets was observed in the T1 animals. No changes in liver enzymes were observed. The increase in eosinophils and platelets found in this experiment suggests that biotherapic ingested by the animals strengthens the defense system and the clotting cascade.Key words: bovinos


    Directory of Open Access Journals (Sweden)

    S. N. Osipov


    Full Text Available Energy security is provided by the minimum required ratio of domestic and imported energy resources. Therefore, in the energy sector energy efficiency should be increased through the use of its own energy resources. Over the last hundred years of development of geological science a preferential distribution of oil and gas fields to areas (blocks of geological faults, many of which reach the surface of the foundation of our planet, has been determined. The complex process of oil and gas formation is predetermined by geological, geochemical, hydrogeological and other factors. The concepts of organic and inorganic origin of oil and gas are also relevant in the context under consideration. The formation of sufficient oil and gas fields is possible in the presence of highly porous and fractured rocks (for oil or so-called gas traps. Promising for the discovery of sufficient oil and gas fields are the central and southern areas of the Pripyat trough and the areas on the borders Mikashevichsi-Zhitkovichi ledge. The geological conditions of the areas in the Southern part of the Podlaska-Brest and the North-Eastern part of the Orsha troughs require most thorough investigations. In the area of the Belarusian anteclise, especially near the Baltic syneclise, at great depths in porous rocks the presence of oil and gas deposits of inorganic origin is possible. The use of plasma-pulse impact (that is a very effective one on the oil and gas underground reservoirs requires a study of the feasibility of their use in new and existing waste deposits. In the exploration of minerals such “exotic” methods, as the assessment of the discharge of helium, radon, radioactive analysis, etc. should also be applied. It is necessary to detect a possible fault zones and prospective search of hydrocarbon energy resources. To ensure energy security of Belarus, the evaluation of the possibility of using associated gas to supply with it a significant part of the country should

  10. Systemic change increases model projection uncertainty (United States)

    Verstegen, Judith; Karssenberg, Derek; van der Hilst, Floor; Faaij, André


    the neighbourhood doubled, while the influence of slope and potential yield decreased by 75% and 25% respectively. Allowing these systemic changes to occur in our CA in the future (up to 2022) resulted in an increase in model projection uncertainty by a factor two compared to the assumption of a stationary system. This means that the assumption of a constant model structure is not adequate and largely underestimates uncertainty in the projection. References Verstegen, J.A., Karssenberg, D., van der Hilst, F., Faaij, A.P.C., 2014. Identifying a land use change cellular automaton by Bayesian data assimilation. Environmental Modelling & Software 53, 121-136. Verstegen, J.A., Karssenberg, D., van der Hilst, F., Faaij, A.P.C., 2012. Spatio-Temporal Uncertainty in Spatial Decision Support Systems: a Case Study of Changing Land Availability for Bioenergy Crops in Mozambique. Computers , Environment and Urban Systems 36, 30-42. Wald, A., Wolfowitz, J., 1940. On a test whether two samples are from the same population. The Annals of Mathematical Statistics 11, 147-162.

  11. ASEAN energy cooperation an increasingly daunting challenge

    Energy Technology Data Exchange (ETDEWEB)

    Nicolas, F.


    East Asia has been the fastest growing region in the world since the early 1980's. Arguably, all countries in the region are set for a period of economic, to some extent demographic, and urban expansion. Since energy is a vital factor in driving economic growth, higher energy consumption can be expected in the coming decades in this part of the world. Although the strong growth is to a large extent due to China, Southeast Asian economies also record stellar economic performances and account for the dramatic rise in energy consumption. The Tokyo-based Asia-Pacific Energy Research Centre (APERC) projects that energy demand in the region (excluding Cambodia, Laos, and Myanmar) will double from 252 million tons of oil equivalent (mtoe) to 525 mtoe between 1999 and 2020. How to best meet this demand poses a range of policy challenges for the region's governments not only at the individual but also at the regional level (Symon 2004). In Southeast Asia (SEA), energy sector development has implications for inter-governmental relations for a number of reasons. First, the pursuit of domestic energy goals can affect neighboring countries, as exemplified for instance by the construction of dams for hydropower in shared river systems in the Greater Mekong Subregion (GMS). Secondly, domestic gas and power systems are expected to be increasingly supported by pipelines and transmission links with other countries, thus opening the possibilities of system integration to meet demand at lower cost. Lastly, with fossil fuels as the primary source of energy supply, problems of environmental degradation as well as of availability (associated in particular with high oil dependency) are doomed to loom large in this part of the world and could be better met through intra-regional cooperation. A major characteristic of the region is the presence of the Association of Southeast Asian Nations (ASEAN), which is the only formal grouping of economic cooperation in Asia. Prima facie

  12. Overexpression of INCREASED CAMBIAL ACTIVITY, a putative methyltransferase, increases cambial activity and plant growth

    Institute of Scientific and Technical Information of China (English)

    Hyunsook Kim; Mikiko Kojima; Daeseok Choi; Soyoung Park; Minami Matsui; Hitoshi Sakakibara; Ildoo Hwang


    Cambial activity is a prerequisite for secondary growth in plants; however, regulatory factors control ing the activity of the secondary meristem in radial growth remain elusive. Here, we identified INCREASED CAMBIAL ACTIVITY (ICA), a gene encoding a putative pectin methyltransferase, which could function as a modulator for the meristematic activity of fascicular and interfascicular cambium in Arabidopsis. An overexpressing transgenic line, 35S::ICA, showed accelerated stem elongation and radial thickening, resulting in increased accumulation of biomass, and increased levels of cytokinins (CKs) and gibberel ins (GAs). Expression of genes encoding pectin methylesterases involved in pectin modification together with pectin methyltransferases was highly induced in 35S::ICA, which might contribute to an increase of methanol emission as a byproduct in 35S::ICA. Methanol treatment induced the expression of GA-or CK-responsive genes and stimulated plant growth. Overal , we propose that ectopic expression of ICA increases cambial activity by regulating CK and GA homeostasis, and methanol emission, eventual y leading to stem elongation and radial growth in the inflorescence stem.

  13. Increased soil emissions of potent greenhouse gases under increased atmospheric CO2. (United States)

    van Groenigen, Kees Jan; Osenberg, Craig W; Hungate, Bruce A


    Increasing concentrations of atmospheric carbon dioxide (CO(2)) can affect biotic and abiotic conditions in soil, such as microbial activity and water content. In turn, these changes might be expected to alter the production and consumption of the important greenhouse gases nitrous oxide (N(2)O) and methane (CH(4)) (refs 2, 3). However, studies on fluxes of N(2)O and CH(4) from soil under increased atmospheric CO(2) have not been quantitatively synthesized. Here we show, using meta-analysis, that increased CO(2) (ranging from 463 to 780 parts per million by volume) stimulates both N(2)O emissions from upland soils and CH(4) emissions from rice paddies and natural wetlands. Because enhanced greenhouse-gas emissions add to the radiative forcing of terrestrial ecosystems, these emissions are expected to negate at least 16.6 per cent of the climate change mitigation potential previously predicted from an increase in the terrestrial carbon sink under increased atmospheric CO(2) concentrations. Our results therefore suggest that the capacity of land ecosystems to slow climate warming has been overestimated.

  14. Does increased local bone resorption secondary to breast and prostate cancer result in increased cartilage degradation?

    DEFF Research Database (Denmark)

    Leeming, Diana J; Byrjalsen, Inger; Qvist, Per


    BACKGROUND: Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover...... in breast and prostate cancer patients is associated with an increase in cartilage degradation and to test in vitro whether osteoclasts or cathepsin K alone generate CTXII from human bone. METHODS: The study included 132 breast and prostate cancer patient, where presence of bone metastases was graded...... according to the Soloway score. Total bone resorption (CTXItotal) and cartilage degradation (CTXII) were determined. RESULTS: Breast and prostate cancer patients with bone metastases revealed significant increased levels of CTXItotal at Soloway scores 1 and higher compared to patients without bone...

  15. Increase in human brain size a key to increase in body size

    Directory of Open Access Journals (Sweden)



    Full Text Available Lucy, considered to be the ancestor to all humanity was a very short creature about three and a half feet tall, weighing some 60 to 65 pounds and lived around 3.2 million years ago in Ethiopia. Perhaps the growth period among the australopithecines was much shorter than that of the modern day humans and hence simply by this yardstick, there has to be a lot of difference in body size between them. The longer the growth period the larger the body size and this is what seemed to happen to the humans during evolutionary history. Recently Mark Grabowski, a researcher at American Museum of Natural History, New York,observed in his research paper that "Bigger brains led to bigger bodies... as over the last four million years, brain size and body size increased substantially in our human ancestors" (Current Anthropology, Vol. 57, 174-196, April 2016. These observations were not new and were clearly understood by the scientific community earlier also. However, numerous hypotheses put forth had emphasized the role of natural selection on different traits independently. But none of them had gone in the direction of a correlated response to natural selection in favour of enlarging the brain size and the body size together. These viewpoints had concluded that increase in brain size and body size were the products of separate natural selection forces. However, Mark Grabowski states that "some genes cause variation in both brain and body size, with the result that selection on either trait can lead to a correlated response in the unselected trait." This is a new explanation to the problem. It highlights the role of correlated outcomes of the natural selection phenomena occurring to one trait but affecting the other trait even if that is not selected for. It is similar to saying that as the brain size increased from Lucy to Homo erectus so did the body size as if the animal pulled itself up and increased in size proportionately as well to keep pace with the

  16. Osteoinductive potential of demineralized rat bone increases with increasing donor age from birth to adulthood

    DEFF Research Database (Denmark)

    Pinholt, E M; Solheim, E


    quantitatively, by uptake of strontium 85, the osteoinductive effect of demineralized bone matrix from newborn, 8-week-old (adolescent), and 8-month-old (adult) male Wistar rats implanted in the abdominal muscles of 8-week-old male Wistar rats. The osteoinductive response increased significantly with increasing......Demineralized allogenic bone implanted in the subcutis or muscle of rodents causes formation of heterotopic bone by osteoinduction. The osteoinductive response may be weaker in primates than in rodents. It was suggested that the osteoinductive response of demineralized bone for clinical use could...

  17. Significant increase of Echinococcus multilocularis prevalencein foxes, but no increased predicted risk for humans

    NARCIS (Netherlands)

    Maas, M.; Dam-Deisz, W.D.C.; Roon, van A.M.; Takumi, K.; Giessen, van der J.W.B.


    The emergence of the zoonotic tapeworm Echinococcus multilocularis, causative agent ofalveolar echinococcosis (AE), poses a public health risk. A previously designed risk mapmodel predicted a spread of E. multilocularis and increasing numbers of alveolar echinococ-cosis patients in the province of L

  18. Increasing pesticide-resistant ectoparasitic infections may increase pesticide poisoning risks in children. (United States)

    Diaz, James H


    Head louse and scabies mite infestations are common among pre-school and school-age children, and topical pesticides are frequently prescribed to treat such conditions. Ectoparasite resistance to the safest and most commonly prescribed pyrethrin/pyrethroid pesticides for ectoparasitic infections has, however, been increasing since the 1980s. The increasing resistance of these arthropods to the safest pesticides may lead to greater use of more toxic, alternative pesticides to control infestations and to prevent institutional outbreaks. MEDLINE and Cochrane searches, 1966-2008, were conducted to assess the impact of increasing pesticide resistance on prescribing practices for ectoparasitic infections and to describe the evolving global epidemiology of pediatric poisonings by more toxic pediculicides and miticides, including carbamates, organochlorines, and organophosphates. Pharmacists, physicians, and poison control personnel should be fully informed about increasing pesticide resistance among the most commonly encountered ectoparasites of children and the institutionalized and be prepared to prevent and to treat accidental home and institutional pesticide poisonings with more toxic pesticides.

  19. Increases in Cognitive and Linguistic Processing Primarily Account for Increases in Speaking Rate with Age (United States)

    Nip, Ignatius S. B.; Green, Jordan R.


    Age-related increases of speaking rate are not fully understood, but have been attributed to gains in biologic factors and learned skills that support speech production. This study investigated developmental changes in speaking rate and articulatory kinematics of participants aged 4 ("N" = 7), 7 ("N" = 10), 10…

  20. Interferon-beta increases systemic BAFF levels in multiple sclerosis without increasing autoantibody production

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Sellebjerg, Finn; Krakauer, Martin


    Background: Treatment with interferon-beta (IFN-beta) increases B-cell activating factor of the TNF family (BAFF) expression in multiple sclerosis (MS), raising the concern that treatment of MS patients with IFN-beta may activate autoimmune B cells and stimulate the production of MS...

  1. ars1, an Arabidopsis mutant exhibiting increased tolerance to arsenate and increased phosphate uptake. (United States)

    Lee, David A; Chen, Alice; Schroeder, Julian I


    Arsenic is one of the most toxic pollutants at contaminated sites, yet little is known about the mechanisms by which certain plants survive exposure to high arsenic levels. To gain insight into the mechanisms of arsenic tolerance in plants, we developed a genetic screen to isolate Arabidopsis thaliana mutants with altered tolerance to arsenic. We report here on the isolation of a mutant arsenic resisant 1 (ars1) with increased tolerance to arsenate. ars1 germinates and develops under conditions that completely inhibit growth of wild-type plants and shows a semi-dominant arsenic resistance phenotype. ars1 accumulates levels of arsenic similar to that accumulated by wild-type plants, suggesting that ars1 plants have an increased ability to detoxify arsenate. However, ars1 plants produce phytochelatin levels similar to levels produced by the wild type, and the enhanced resistance of ars1 is not abolished by the gamma-glutamylcysteine synthetase inhibitor l-buthionine sulfoxime (BSO). Furthermore, ars1 plants do not show resistance to arsenite or other toxic metals such as cadmium and chromium. However, ars1 plants do show a higher rate of phosphate uptake than that shown by wild-type plants, and wild-type plants grown with an excess of phosphate show increased tolerance to arsenate. Traditional models of arsenate tolerance in plants are based on the suppression of phosphate uptake pathways and consequently on the reduced uptake of arsenate. Our data suggest that arsenate tolerance in ars1 could be due to a new mechanism mediated by increased phosphate uptake in ars1. Models discussing how increased phosphate uptake could contribute to arsenate tolerance are discussed.

  2. Vulnerability Assessment of Housing Damage in the Philippines Due to an Increase Increase in Typhoon Intensity (United States)

    Esteban, Miguel; Stromberg, Per; Gasparatos, Alexandros


    It is currently feared that the increase in surface sea temperature resulting from increasing level of greenhouse gases in the atmosphere could result in higher tropical cyclone intensity in the future. Although the vulnerability of infrastructure and economic systems have been studied for a number of developed countries, very little work has been done on developing countries. The present work first attempts to evaluate the vulnerability of different regions in the Philippines to the passage of tropical cyclones. To this effect a total of 22 typhoons and tropical storms that affected the Philippines were analysed for the period 2003-2008. The data used was collected by the National Disaster Coordinating Council of the Philippines, who issue "SitRep" NDCC Reports after each major storm. This agency provides damage data for each region, including number of casualties, affected people, damaged and destroyed houses, and losses in the infrastructure and agriculture. The likely economic effects of increased typhoon intensity by using a Monte Carlo Simulation that magnifies the intensity of historical tropical cyclones between the years 1978 and 2008 to simulate the economic damage by 2085. The methodology used is based on the work of Esteban et al. (2009), which in turn uses the results of Knutson and Tuleya (2004) for the estimation of the increase in tropical cyclone intensity in 2085. The results show that downtime could increase from a national 1% to 1.3% by 2050 if economic and population growth are taken into account (29 to 36bn USD, from a total GDP of 2,757bn USD by 2050). If these are ignored the time lost each year can be estimated to cost around 630m USD (PPP) for the control scenario, which could increase to between 766m or 945mm USD by the year 2085 for the two different scenarios considered. This indirect damage depends on the geographical location and is for example higher in some areas of the northern island of Luzon, while the island of Mindanao in the

  3. Strangers With Benefits: Attraction to Outgroup Men Increases as Fertility Increases Across the Menstrual Cycle. (United States)

    Salvatore, Joseph F; Meltzer, Andrea L; March, David S; Gaertner, Lowell


    Research typically reveals that outgroups are regarded with disinterest at best and hatred and enmity at worst. Working from an evolutionary framework, we identify a unique pattern of outgroup attraction. The small-group lifestyle of pre-human ancestors plausibly limited access to genetically diverse mates. Ancestral females may have solved the inbreeding dilemma while balancing parental investment pressures by mating with outgroup males either via converting to an outgroup or cuckolding the ingroup. A vestige of those mating strategies might manifest in human women as a cyclic pattern of attraction across the menstrual cycle, such that attraction to outgroup men increases as fertility increases across the cycle. Two studies, one using a longitudinal method and the other an experimental method, evidenced the hypothesized linear relationship between attraction to outgroup men and fertility in naturally cycling women.

  4. Increased familiarity with eating a food to fullness underlies increased expected satiety. (United States)

    Irvine, Michael A; Brunstrom, Jeffrey M; Gee, Philip; Rogers, Peter J


    Expected satiety informs self-selected portion sizes and thereby influences energy intake. At present the extent to which these beliefs are learned remains unclear. In an initial study the proposition that familiarity influences expected satiety was explored. Self-report measures of familiarity, along with other measures such as degree of liking, were collected for wine gums and milk chocolate, together with expected satiety estimates obtained using a psychophysical task. Familiarity was indeed significantly correlated with expected satiety, but only in respect of frequency of having eaten the food to fullness. In a second experiment a significant increase in expected satiety was observed after eating a large portion of wine gums at a subsequent test session. Together, these findings indicate that expected satiety changes in response to increased familiarity of eating a food to satiety.

  5. Does the risk of cerebral palsy increase or decrease with increasing gestational age?

    Directory of Open Access Journals (Sweden)

    Murphy-Kaulbeck Lynn


    Full Text Available Abstract Background It is generally accepted that the risk of cerebral palsy decreases with increasing gestational age of live born infants. However, recent studies have shown that cerebral palsy often has prenatal antecedents including congenital malformations, vascular insults and maternal infection. Cerebral palsy is therefore better viewed as occurring among fetuses, rather than among infants. We explored the epidemiologic implications of this change in perspective. Methods We used recently published data from Shiga Prefecture, Japan and from North-East England to examine the pattern of gestational age-specific rates of cerebral palsy under these alternative perspectives. We first calculated gestational age-specific rates of cerebral palsy as per convention, by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of live births in that gestational age category. Under the alternative formulation, we calculated gestational age-specific rates of cerebral palsy by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of fetuses who were at risk of being born at that gestation and being afflicted with cerebral palsy. Results Under the conventional formulation, cerebral palsy rates decreased with increasing gestational age from 63.9 per 1,000 live births at Conclusions The fetuses-at-risk approach is the appropriate epidemiologic formulation for calculating the gestational age-specific rate of cerebral palsy from a causal perspective. It shows that the risk of cerebral palsy increases as gestational duration increases. This compelling view of cerebral palsy risk may help refocus research aimed at understanding and preventing cerebral palsy.

  6. Preconditions that Affect in Increasing Control Effect and Increased Chance for Tax Fraud Detection


    Mentor Gashi; Nexhit Shala


    Abstract:In this research we have submitted seven elements in order to identify the most powerful elements that increases the chances of detecting fraud or tax evasion, from retroactive control. Elements that have submitted in the research are:Professionalism of the officer who realizes control or tax audit; Integrity of  Officer  that realizes control or audit; Information from their competitor, with the aim of informing about tax evasion; Information from a dissatisfied employee or former e...

  7. Chromosome 1 replacement increases brain orexins and antidepressive measures without increasing locomotor activity. (United States)

    Feng, Pingfu; Hu, Yufen; Vurbic, Drina; Akladious, Afaf; Strohl, Kingman P


    Decreased orexin level has been well demonstrated in patients suffering from narcolepsy, depression accompanied with suicide attempt; obstructive sleep apnea and comorbidity were also demonstrated in these diseases. As C57BL/6J (B6) mice are more "depressed" and have lower brain orexins than A/J mice, B6 mice having chromosome 1 replacement (B6A1 mice) might have restored orexin levels and less depressive behavior. We studied the behavior of 4-6 month old B6, A/J and B6A1 mice with forced swim, tail suspension, and locomotor activity tests. The animals were then sacrificed and hypothalamus and medullas dissected from brain tissue. Orexins-A and -B were determined by radioimmunoassay. Compared with A/J mice, B6 mice displayed several signs of depression, including increased immobility, increased locomotors activity, and decreased orexin A and -B levels in both the hypothalamus and medulla. Compared to B6 mice, B6A1 mice exhibited significantly higher levels of orexins-A and -B in both brain regions. B6A1 mice also exhibited antidepressive features in most of measured variables, including decreased locomotor activity, decreased immobility and increased swim in tail suspension test; compared with B6 mice, however. B6A1 mice also reversed immobility in the early phase of the swim test. In summary, B6 mice exhibited depressive attributes compared with A/J mice, including increased locomotor activity, greater immobility, and decreased brain orexins, these were largely reversed in B6A1 mice. We conclude that orexin levels modulate these B6 behaviors, likely due to expression of A/J alleles on Chromosome 1.

  8. Increasing pro-environmental behaviors by increasing self-concordance: Testing an intervention. (United States)

    Unsworth, Kerrie L; McNeill, Ilona M


    Globally, there is a clear need to change our behavior to mitigate climate change. Many people, however, will not find the need for mitigation important enough to make their behavior more environmentally sustainable. Three studies supported the hypothesis that it is possible to overcome this issue by connecting these behaviors to goals that are important to people, even if such goals are unrelated to climate change or the environment in general. Study 1 (N = 305 working adults) showed that stronger self-concordance of behavior related to energy sustainability was related to a greater chance of signing a petition for increasing renewable energy sources. Next, 2 experimental studies (Study 2: N = 412 working and nonworking adults, and Study 3: N = 300 working adults) showed that increasing self-concordance of environmentally sustainable behaviors by asking people to cognitively connect either sustainable energy use (Study 2) or commuting behaviors (Study 3) to their personal goals increased intentions to engage in these behaviors compared to a control condition (Study 2 and Study 3) and compared to persuasion attempts based on climate change mitigation (Study 3). These findings occurred even after controlling for political orientation and environmental concerns. This research has significant practical implications for workplaces, particularly for those in which employees or managers place a low priority on environmental and climate change considerations. (PsycINFO Database Record

  9. Preconditions that Affect in Increasing Control Effect and Increased Chance for Tax Fraud Detection

    Directory of Open Access Journals (Sweden)

    Mentor Gashi


    Full Text Available Abstract:In this research we have submitted seven elements in order to identify the most powerful elements that increases the chances of detecting fraud or tax evasion, from retroactive control. Elements that have submitted in the research are:Professionalism of the officer who realizes control or tax audit; Integrity of  Officer  that realizes control or audit; Information from their competitor, with the aim of informing about tax evasion; Information from a dissatisfied employee or former employee; Information from freight forwarding; Informatat from accountant; Information from the data exchange with the export country. Elements that we presented, are the most powerful elements that increases the chances of detection of tax evasion, such as: professionalism of the officer who implements control or audit, which follows two other elements, which are: Integrity of official that realizes control or audit and the information are data exchange with the export country, these are the three most powerful elements until four other elements outlined in the survey have less impact compared with the three elements mentioned. The purpose of the paper is to Find the most powerful elements that increase the probability of detecting of tax evasion or tax fraud from retroactive controls. Methodology: Survey was realize through questionnaires, which were distributed 232 questionnaires. Questionnaires were distributed mainly to the importing companies, officers that realize controls to businesses, customs agents, accountants and international transport companie. Key words: probability of detecting, tax evasion, control or audit

  10. Increased signaling through p62 in the marrow microenvironment increases myeloma cell growth and osteoclast formation (United States)

    Hiruma, Yuko; Honjo, Tadashi; Jelinek, Diane F.; Windle, Jolene J.; Shin, Jaekyoon; Roodman, G. David


    Adhesive interactions between multiple myeloma (MM) cells and marrow stromal cells activate multiple signaling pathways including nuclear factor κB (NF-κB), p38 mitogen-activated protein kinase (MAPK), and Jun N-terminal kinase (JNK) in stromal cells, which promote tumor growth and bone destruction. Sequestosome-1 (p62), an adapter protein that has no intrinsic enzymatic activity, serves as a platform to facilitate formation of signaling complexes for these pathways. Therefore, we determined if targeting only p62 would inhibit multiple signaling pathways activated in the MM microenvironment and thereby decrease MM cell growth and osteoclast formation. Signaling through NF-κB and p38 MAPK was increased in primary stromal cells from MM patients. Increased interleukin-6 (IL-6) production by MM stromal cells was p38 MAPK-dependent while increased vascular cell adhesion molecule-1 (VCAM-1) expression was NF-κB–dependent. Knocking-down p62 in patient-derived stromal cells significantly decreased protein kinase Cζ (PKCζ), VCAM-1, and IL-6 levels as well as decreased stromal cell support of MM cell growth. Similarly, marrow stromal cells from p62−/− mice produced much lower levels of IL-6, tumor necrosis factor-α (TNF-α), and receptor activator of NF-κB ligand (RANKL) and supported MM cell growth and osteoclast formation to a much lower extent than normal cells. Thus, p62 is an attractive therapeutic target for MM. PMID:19282458

  11. Increasing native, but not exotic, biodiversity increases aboveground productivity in ungrazed and intensely grazed grasslands. (United States)

    Isbell, Forest I; Wilsey, Brian J


    Species-rich native grasslands are frequently converted to species-poor exotic grasslands or pastures; however, the consequences of these changes for ecosystem functioning remain unclear. Cattle grazing (ungrazed or intensely grazed once), plant species origin (native or exotic), and species richness (4-species mixture or monoculture) treatments were fully crossed and randomly assigned to plots of grassland plants. We tested whether (1) native and exotic plots exhibited different responses to grazing for six ecosystem functions (i.e., aboveground productivity, light interception, fine root biomass, tracer nitrogen uptake, biomass consumption, and aboveground biomass recovery), and (2) biodiversity-ecosystem functioning relationships depended on grazing or species origin. We found that native and exotic species exhibited different responses to grazing for three of the ecosystem functions we considered. Intense grazing decreased fine root biomass by 53% in exotic plots, but had no effect on fine root biomass in native plots. The proportion of standing biomass consumed by cattle was 16% less in exotic than in native grazed plots. Aboveground biomass recovery was 30% less in native than in exotic plots. Intense grazing decreased aboveground productivity by 25%, light interception by 14%, and tracer nitrogen uptake by 54%, and these effects were similar in native and exotic plots. Increasing species richness from one to four species increased aboveground productivity by 42%, and light interception by 44%, in both ungrazed and intensely grazed native plots. In contrast, increasing species richness did not influence biomass production or resource uptake in ungrazed or intensely grazed exotic plots. These results suggest that converting native grasslands to exotic grasslands or pastures changes ecosystem structure and processes, and the relationship between biodiversity and ecosystem functioning.

  12. Increased Lipiodol uptake in hepatocellular carcinoma possibly due to increased membrane fluidity by dexamethasone and tamoxifen

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Stephanie, E-mail: stephanie.becker@rouen.fnclcc.f [Department of Nuclear Medicine, Centre E. Marquis, F-35042 Rennes (France); INSERM U 991, Rennes, F-35033 France (France); European University of Brittany, F-35000 Rennes (France); Department of Nuclear Medicine, Centre H. Becquerel, F-76038 Rouen (France); Ardisson, Valerie; Lepareur, Nicolas [Department of Nuclear Medicine, Centre E. Marquis, F-35042 Rennes (France); INSERM U 991, Rennes, F-35033 France (France); European University of Brittany, F-35000 Rennes (France); Sergent, Odile [European University of Brittany, F-35000 Rennes (France); UPRES EA SeRAIC, IFR 140, University of Rennes 1, F-35043 Rennes (France); Bayat, Sahar [INSERM U936 Department of Biostatistics, CHRU Pontchaillou, F-35033 Rennes (France); Noiret, Nicolas [European University of Brittany, F-35000 Rennes (France); Ecole Nationale Superieure de Chimie de Rennes, UMR CNRS 6226, F-35708 Rennes (France); Gaboriau, Francois; Clement, Bruno [INSERM U 991, Rennes, F-35033 France (France); Boucher, Evelyne [INSERM U 991, Rennes, F-35033 France (France); Department of Medical Oncology, Centre E. Marquis, F-35042 Rennes (France); Raoul, Jean-Luc [INSERM U 991, Rennes, F-35033 France (France); European University of Brittany, F-35000 Rennes (France); Department of Medical Oncology, Centre E. Marquis, F-35042 Rennes (France); Garin, Etienne [Department of Nuclear Medicine, Centre E. Marquis, F-35042 Rennes (France); INSERM U 991, Rennes, F-35033 France (France); European University of Brittany, F-35000 Rennes (France)


    Introduction: Lipiodol is used as a vector for chemoembolization or internal radiotherapy in unresectable hepatocellular carcinomas (HCCs). The aim of this study is to improve the tumoral uptake of Lipiodol by modulating membrane fluidizing agents to optimize the effectiveness of Lipiodol vectorized therapy. Methods: The effect of dexamethasone and tamoxifen on membrane fluidity was studied in vitro by electron paramagnetic resonance applied to rat hepatocarcinoma cell line N1S1. The tumoral uptake of Lipiodol was studied in vivo on rats with HCC, which had been previously treated by dexamethasone and/or tamoxifen, after intra-arterial administration of {sup 99m}Tc-SSS-Lipiodol. Results: The two molecules studied here exhibit a fluidizing effect in vitro which appears dependent on time and dose, with a maximum fluidity obtained after 1 hr at concentrations of 20 {mu}M for dexamethasone and 200 nM for tamoxifen. In vivo, while the use of dexamethasone or tamoxifen alone tends to lead to increased tumoral uptake of Lipiodol, this effect does not reach levels of significance. On the other hand, there is a significant increase in the tumoral uptake of {sup 99m}Tc-SSS-Lipiodol in rats pretreated by both dexamethasone and tamoxifen, with a tumoral uptake (expressed in % of injected activity per g of tumor) of 13.57{+-}3.65% after treatment, as against 9.45{+-}4.44% without treatment (P<.05). Conclusions: Dexamethasone and tamoxifen fluidify the N1S1 cells membrane, leading to an increase in the tumoral uptake of Lipiodol. These drugs could be combined with chemo-Lipiodol-embolization or radiolabeled Lipiodol, with a view to improving the effectiveness of HCCs therapy.

  13. Chronic opioid use is associated with increased DNA methylation correlating with increased clinical pain. (United States)

    Doehring, Alexandra; Oertel, Bruno Georg; Sittl, Reinhard; Lötsch, Jörn


    Environmentally caused changes in chromosomes that do not alter the DNA sequence but cause phenotypic changes by altering gene transcription are summarized as epigenetics. A major epigenetic mechanism is methylation or demethylation at CpG-rich DNA islands. DNA methylation triggered by drugs has largely unexplored therapeutic consequences. Here we report increased methylation at a CpG rich island in the OPRM1 gene coding for μ-opioid receptors and at a global methylation site (LINE-1) in leukocytes of methadone-substituted former opiate addicts compared with matched healthy controls. Higher DNA methylation associated with chronic opioid exposure was reproduced in an independent cohort of opioid-treated as compared to non-opioid-treated pain patients. This suggests that opioids may stimulate DNA methylation. The OPRM1 methylation had no immediate effect on μ-opioid receptor transcription and was not associated with opioid dosing requirements. However, the global DNA methylation at LINE-1 was significantly correlated with increased chronic pain. This suggests inhibitory effects on the transcription of still unspecified nocifensive gene products. It further implies that opioids may be causally associated with increased genome-wide DNA methylation, although currently there is no direct evidence of this. This has phenotypic consequences for pain and may provide a new, epigenetics-associated mechanism of opioid-induced hyperalgesia. The results indicate a potential influence of opioid analgesics on the patients' epigenome. They emphasize the need for reliable and cost-effective screening tools and may imply that high-throughput screening for lead compounds in artificial expression systems may not provide the best tools for identifying new pain medications.

  14. Chromosome numbers in three species groups of freshwater flatworms increase with increasing latitude. (United States)

    Lorch, Sven; Zeuss, Dirk; Brandl, Roland; Brändle, Martin


    Polyploidy in combination with parthenogenesis offers advantages for plasticity and the evolution of a broad ecological tolerance of species. Therefore, a positive correlation between the level of ploidy and increasing latitude as a surrogate for environmental harshness has been suggested. Such a positive correlation is well documented for plants, but examples for animals are still rare. Species of flatworms (Platyhelminthes) are widely distributed, show a remarkably wide range of chromosome numbers, and offer therefore good model systems to study the geographical distribution of chromosome numbers. We analyzed published data on counts of chromosome numbers and geographical information of three flatworm "species" (Phagocata vitta, Polycelis felina and Crenobia alpina) sampled across Europe (220 populations). We used the mean chromosome number across individuals of a population as a proxy for the level of ploidy within populations, and we tested for relationships of this variable with latitude, mode of reproduction (sexual, asexual or both) and environmental variables (annual mean temperature, mean diurnal temperature range, mean precipitation and net primary production). The mean chromosome numbers of all three species increased with latitude and decreased with mean annual temperature. For two species, chromosome number also decreased with mean precipitation and net primary production. Furthermore, high chromosome numbers within species were accompanied with a loss of sexual reproduction. The variation of chromosome numbers within individuals of two of the three species increased with latitude. Our results support the hypothesis that polyploid lineages are able to cope with harsh climatic conditions at high latitudes. Furthermore, we propose that asexual reproduction in populations with high levels of polyploidization stabilizes hybridization events. Chromosomal irregularities within individuals tend to become more frequent at the extreme environments of high

  15. Increases in New Social Network Ties are Associated with Increased Cohesion among Intervention Participants (United States)

    Gesell, Sabina B.; Barkin, Shari L.; Sommer, Evan C.; Thompson, Jessica R.; Valente, Thomas W.


    Objective Many behavior change programs are delivered in group settings to manage implementation costs and to foster support and interactions among group members to facilitate behavior change. Understanding the group dynamics that evolve in group settings (e.g., weight management, Alcoholics Anonymous) is important, yet rarely measured. This paper examined the relationship between social network ties and group cohesion in a group-based intervention to prevent obesity in children. Method The data reported are process measures from an ongoing community-based randomized controlled trial. 305 parents with a child (3-6 years) at risk of developing obesity were assigned to an intervention that taught parents healthy lifestyles. Parents met weekly for 12 weeks in small consistent groups. Two measures were collected at weeks 3 and 6: a social network survey (people in the group with whom one discusses healthy lifestyles); and the validated Perceived Cohesion Scale (Bollen & Hoyle, 1990). We used lagged random and fixed effects regression models to analyze the data. Results Cohesion increased from 6.51 to 6.71 (t=4.4, p<0.01). Network nominations tended to increase over the 3-week period in each network. In the combined discussion and advice network, the number of nominations increased from 1.76 to 1.95 (z=2.59, p<0.01). Cohesion at week 3 was the strongest predictor of cohesion at week 6 (b=0.55, p<0.01). Number of new network nominations at week 6 was positively related to cohesion at week 6 (b=0.06, p<.01). In sum, being able to name new network contacts was associated with feelings of cohesion. Conclusion This is the first study to demonstrate how network changes affect perceived group cohesion within a behavioral intervention. Given that many behavioral interventions occur in group settings, intentionally building new social networks could be promising to augment desired outcomes. PMID:26286298

  16. Sagittal rotational stiffness and damping increase in a porcine lumbar spine with increased or prolonged loading. (United States)

    Zondervan, Robert L; Popovich, John M; Radcliffe, Clark J; Pathak, Pramod K; Reeves, N Peter


    While the impact of load magnitude on spine dynamic parameters (stiffness and damping) has been reported, it is unclear how load history (exposure to prolonged loading) affects spine dynamic parameters in sagittal rotation. Furthermore, it is unknown if both spine stiffness and damping are equally affected to prolonged loading. Using a pendulum testing apparatus, the effect of load magnitude and load history on spine sagittal rotational stiffness and damping was assessed. Nine porcine lumbar functional spine units (FSUs) were tested in an increasing compressive load phase (ICP: 44.85, 68.55, 91.75, 114.6kg) and then a decreasing compressive load phase (DCP: 91.75, 68.55, and 44.85kg). Each trial consisted of flexing the FSU 5° and allowing it to oscillate unconstrained. During the ICP, both stiffness and damping linearly increased with load. However, in the DCP, stiffness and damping values were significantly higher than the identical load collected during the ICP, suggesting load history affects sagittal rotational dynamic parameters. In addition, spine damping was more affected by load history than spine stiffness. These results highlight the importance of controlling load magnitude and history when assessing spine dynamic parameters.

  17. Evolution of increased larval competitive ability in Drosophila melanogaster without increased larval feeding rate

    Indian Academy of Sciences (India)



    Multiple experimental evolution studies on Drosophila melanogasterin the 1980s and 1990s indicated that enhanced competitive ability evolved primarily through increased larval tolerance to nitrogenous wastes and increased larval feeding and foraging rate, at the cost of efficiency of food conversion to biomass, and this became the widely accepted view of how adaptation to larval crowding evolves in fruitflies. We recently showed that populations of D. ananassaeand D. n. nasuta subjected to extreme larval crowding evolved greater competitive ability without evolving higher feeding rates, primarily through acombination of reduced larval duration, faster attainment of minimum critical size for pupation, greater efficiency of food conversion to biomass, increased pupation height and, perhaps, greater urea/ammonia tolerance. This was a very differentsuite of traits than that seen to evolve under similar selection in D. melanogasterand was closer to the expectations from the theory of K-selection. At that time, we suggested two possible reasons for the differences in the phenotypic correlates ofgreater competitive ability seen in the studies with D. melanogaster and the other two species. First, that D. ananassae and D. n. nasuta had a very different genetic architecture of traits affecting competitive ability compared to the long-term labora-tory populations of D. melanogaster used in the earlier studies, either because the populations of the former two species were relatively recently wild-caught, or by virtue of being different species. Second, that the different evolutionary trajectories in D. ananassae and D. n. nasuta versus D. melanogaster were a reflection of differences in the manner in which larval crowding was imposed in the two sets of selection experiments. The D. melanogaster studies used a higher absolute density of eggs per unit volume of food, and a substantially larger total volume of food, than the studies on D. ananassae and D. n. nasuta. Here, we

  18. Evolution of increased larval competitive ability in Drosophila melanogaster without increased larval feeding rate. (United States)

    Sarangi, Manaswini; Nagarajan, Archana; Dey, Snigdhadip; Bose, Joy; Joshi, Amitabh


    Multiple experimental evolution studies on Drosophila melanogaster in the 1980s and 1990s indicated that enhanced competitive ability evolved primarily through increased larval tolerance to nitrogenous wastes and increased larval feeding and foraging rate, at the cost of efficiency of food conversion to biomass, and this became the widely accepted view of how adaptation to larval crowding evolves in fruitflies.We recently showed that populations of D. ananassae and D. n. nasuta subjected to extreme larval crowding evolved greater competitive ability without evolving higher feeding rates, primarily through a combination of reduced larval duration, faster attainment of minimum critical size for pupation, greater efficiency of food conversion to biomass, increased pupation height and, perhaps, greater urea/ammonia tolerance. This was a very different suite of traits than that seen to evolve under similar selection in D. melanogaster and was closer to the expectations from the theory of K-selection. At that time, we suggested two possible reasons for the differences in the phenotypic correlates of greater competitive ability seen in the studies with D. melanogaster and the other two species. First, that D. ananassae and D. n. nasuta had a very different genetic architecture of traits affecting competitive ability compared to the long-term laboratory populations of D. melanogaster used in the earlier studies, either because the populations of the former two species were relatively recently wild-caught, or by virtue of being different species. Second, that the different evolutionary trajectories in D. ananassae and D. n. nasuta versus D. melanogaster were a reflection of differences in the manner in which larval crowding was imposed in the two sets of selection experiments. The D. melanogaster studies used a higher absolute density of eggs per unit volume of food, and a substantially larger total volume of food, than the studies on D. ananassae and D. n. nasuta. Here, we

  19. Reducing consistency in human realism increases the uncanny valley effect; increasing category uncertainty does not. (United States)

    MacDorman, Karl F; Chattopadhyay, Debaleena


    Human replicas may elicit unintended cold, eerie feelings in viewers, an effect known as the uncanny valley. Masahiro Mori, who proposed the effect in 1970, attributed it to inconsistencies in the replica's realism with some of its features perceived as human and others as nonhuman. This study aims to determine whether reducing realism consistency in visual features increases the uncanny valley effect. In three rounds of experiments, 548 participants categorized and rated humans, animals, and objects that varied from computer animated to real. Two sets of features were manipulated to reduce realism consistency. (For humans, the sets were eyes-eyelashes-mouth and skin-nose-eyebrows.) Reducing realism consistency caused humans and animals, but not objects, to appear eerier and colder. However, the predictions of a competing theory, proposed by Ernst Jentsch in 1906, were not supported: The most ambiguous representations-those eliciting the greatest category uncertainty-were neither the eeriest nor the coldest.

  20. Behavioral and neural correlates of increased self-control in the absence of increased willpower. (United States)

    Magen, Eran; Kim, Bokyung; Dweck, Carol S; Gross, James J; McClure, Samuel M


    People often exert willpower to choose a more valuable delayed reward over a less valuable immediate reward, but using willpower is taxing and frequently fails. In this research, we demonstrate the ability to enhance self-control (i.e., forgoing smaller immediate rewards in favor of larger delayed rewards) without exerting additional willpower. Using behavioral and neuroimaging data, we show that a reframing of rewards (i) reduced the subjective value of smaller immediate rewards relative to larger delayed rewards, (ii) increased the likelihood of choosing the larger delayed rewards when choosing between two real monetary rewards, (iii) reduced the brain reward responses to immediate rewards in the dorsal and ventral striatum, and (iv) reduced brain activity in the dorsolateral prefrontal cortex (a correlate of willpower) when participants chose the same larger later rewards across the two choice frames. We conclude that reframing can promote self-control while avoiding the need for additional willpower expenditure.

  1. Increased endogenous DNA oxidation correlates to increased iron levels in melanocytes relative to keratinocytes. (United States)

    Pelle, Edward; Huang, Xi; Zhang, Qi; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna


    The endogenous oxidative state of normal human epidermal melanocytes was investigated and compared to normal human epidermal keratinocytes (NHEKs) in order to gain new insight into melanocyte biology. Previously, we showed that NHEKs contain higher levels of hydrogen peroxide (H2O2) than melanocytes and that it can migrate from NHEKs to melanocytes by passive permeation. Nevertheless, despite lower concentrations of H2O2, we now report higher levels of oxidative DNA in melanocytes as indicated by increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG): 4.49 (±0.55 SEM) 8-oxo-dG/10(6) dG compared to 1.49 (±0.11 SEM) 8-oxo-dG/10(6) dG for NHEKs. An antioxidant biomarker, glutathione (GSH), was also lower in melanocytes (3.14 nmoles (±0.15 SEM)/cell) in comparison to NHEKs (5.98 nmoles (±0.33 SEM)/cell). Intriguingly, cellular bioavailable iron as measured in ferritin was found to be nearly fourfold higher in melanocytes than in NHEKs. Further, ferritin levels in melanocytes were also higher than in hepatocarcinoma cells, an iron-rich cell, and it indicates that higher relative iron levels may be characteristic of melanocytes. To account for the increased oxidative DNA and lower GSH and H2O2 levels that we observe, we propose that iron may contribute to higher levels of oxidation by reacting with H2O2 through a Fenton reaction leading to the generation of DNA-reactive hydroxyl radicals. In conclusion, our data support the concept of elevated oxidation and high iron levels as normal parameters of melanocytic activity. We present new evidence that may contribute to our understanding of the melanogenic process and lead to the development of new skin care products.

  2. Coastal vegetation invasion increases greenhouse gas emission from wetland soils but also increases soil carbon accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yaping [Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystem, College of the Environment and Ecology, Xiamen University, Xiamen 361102, Fujian (China); Chen, Guangcheng [Third Institute of Oceanography, State Oceanic Administration, Xiamen 361005, Fujian (China); Ye, Yong, E-mail: [Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystem, College of the Environment and Ecology, Xiamen University, Xiamen 361102, Fujian (China)


    Soil properties and soil–atmosphere fluxes of CO{sub 2}, CH{sub 4} and N{sub 2}O from four coastal wetlands were studied throughout the year, namely, native Kandelia obovata mangrove forest vs. exotic Sonneratia apetala mangrove forest, and native Cyperus malaccensis salt marsh vs. exotic Spartina alterniflora salt marsh. Soils of the four wetlands were all net sources of greenhouse gases while Sonneratia forest contributed the most with a total soil–atmosphere CO{sub 2}-equivalent flux of 137.27 mg CO{sub 2} m{sup −2} h{sup −1}, which is 69.23%, 99.75% and 44.56% higher than that of Kandelia, Cyperus and Spartina, respectively. The high underground biomass and distinctive root structure of Sonneratia might be responsible for its high greenhouse gas emission from the soil. Soils in Spartina marsh emitted the second largest amount of total greenhouse gases but it ranked first in emitting trace greenhouse gases. Annual average CH{sub 4} and N{sub 2}O fluxes from Spartina soil were 13.77 and 1.14 μmol m{sup −2} h{sup −1}, respectively, which are 2.08 and 1.46 times that of Kandelia, 1.03 and 1.15 times of Sonneratia, and 1.74 and 1.02 times of Cyperus, respectively. Spartina has longer growing season and higher productivity than native marshes which might increase greenhouse gas emission in cold seasons. Exotic wetland soils had higher carbon stock as compared to their respective native counterparts but their carbon stocks were offset by a larger proportion because of their higher greenhouse gas emissions. Annual total soil–atmosphere fluxes of greenhouse gases reduced soil carbon burial benefits by 8.1%, 9.5%, 6.4% and 7.2% for Kandelia, Sonneratia, Cyperus and Spartina, respectively, which narrowed down the gaps in net soil carbon stock between native and exotic wetlands. The results indicated that the invasion of exotic wetland plants might convert local coastal soils into a considerable atmospheric source of greenhouse gases although they at the

  3. Increased Dietary Inflammatory Index (DII) Is Associated With Increased Risk of Prostate Cancer in Jamaican Men (United States)

    Shivappa, Nitin; Jackson, Maria D.; Bennett, Franklyn; Hébert, James R.


    Purpose Prostate cancer is the most common non-skin malignancy; and it accounts for the most cancer deaths among Jamaican males. Diet has been implicated in the etiology of prostate cancer, including through its effects on inflammation. Method We examined the association between a newly developed dietary inflammatory index (DII) and prostate cancer in a case-control study of 40-80 year-old Jamaican males. A total of 229 incident cases and 250 controls attended the same urology out-patient clinics at 2 major hospitals and private practitioners in the Kingston, Jamaica Metropolitan area between March 2005 and July 2007. The DII was computed based on dietary intake assessed using a previously validated food frequency questionnaire (FFQ) that was expanded to assess diet and cancer in this Jamaican population. Multivariable logistic regression was used to estimate odds ratios, with DII as continuous and expressed as quartiles. Logistic regression analysis adjusted for age, total energy intake, education, body mass index (BMI), smoking status, physical activity and family history of prostate cancer. Results Men in the highest quartile of the DII were at higher risk of prostate cancer [odds ratio (OR) = 2.39; 95% confidence interval (CI) =1.14–5.04 (Ptrend = 0.08)] compared to men in the lowest DII quartile. Conclusion These data suggest a pro-inflammatory diet, as indicated by increasing DII score, may be a risk factor for prostate cancer in Jamaican men. PMID:26226289

  4. Causes and consequences of increased sympathetic activity in renal disease

    NARCIS (Netherlands)

    Joles, JA; Koomans, HA


    Much evidence indicates increased sympathetic nervous activity (SNA) in renal disease. Renal ischemia is probably a primary event leading to increased SNA. Increased SNA often occurs in association with hypertension. However, the deleterious effect of increased SNA on the diseased kidney is not only




    In 1996 Michael Lynn introduced the idea that restaurant managers could increase tips for their waiters and thus increase turnover by training the waiters to engage tip-enhancing behaviours. Since then, the list of tip-enhancing behaviours has expanded. Therefore the potential to increase tips is more accessible. The purpose of this paper was to examine how Slovenian dealers use strategies to increase their tips. We tested fourteen techniques to increase tips. The study was carried out am...

  6. Increased transvascular low density lipoprotein transport in insulin dependent diabetes

    DEFF Research Database (Denmark)

    Kornerup, Karen; Nordestgaard, Børge Grønne; Feldt-Rasmussen, Bo


    BACKGROUND: The increased risk of atherosclerosis associated with diabetes cannot be explained by conventional cardiovascular risk factors alone. We hypothesized that transvascular lipoprotein transport may be increased in patients with diabetes, possibly explaining increased intimal lipoprotein ...... be increased in patients with type 1 diabetes. This suggests that lipoprotein flux into the arterial wall is increased in people with type 1 diabetes, possibly explaining accelerated development of atherosclerosis....

  7. Fiber: How to Increase the Amount in Your Diet (United States)

    ... Fiber: How to Increase the Amount in Your Diet Fiber: How to Increase the Amount in Your Diet ... in the digestive tract) and irritable bowel syndrome. Dietary fiber may also help lower your cholesterol and reduce ...

  8. The Pro-collusive Effect of Increased Cartel Detection Probabilities


    Hinloopen, Jeroen


    An increase in cartel discovery probability due to irregular price movements that result from cartel defection is shown to increase cartel stability as short-run defection profits are less likely to be earned.

  9. Increasing fill volume reduces cardiac performance in peritoneal dialysis

    DEFF Research Database (Denmark)

    Ivarsen, Per; Povlsen, Johan V; Jensen, Jens Dam


    BACKGROUND: It is generally accepted that peritoneal dialysis (PD) affects systemic haemodynamics less than haemodialysis, but little is known about changes in haemodynamics during PD. It is unknown if increasing PD volume causes changes in cardiovascular haemodynamics possibly increasing...

  10. Who Is at Increased Risk of Health Problems during Pregnancy? (United States)

    ... is at increased risk of health problems during pregnancy? Skip sharing on social media links Share this: Page Content Some women are at increased risk for health problems during pregnancy. Important risk factors include the following: Overweight and ...

  11. Increasing risk of prosthetic joint infection after total hip arthroplasty

    DEFF Research Database (Denmark)

    Dale, Håvard; Fenstad, Anne M; Hallan, Geir;


    Background and purpose The risk of revision due to infection after primary total hip arthroplasty (THA) has been reported to be increasing in Norway. We investigated whether this increase is a common feature in the Nordic countries (Denmark, Finland, Norway, and Sweden). Materials and methods The...... explain this increase. We believe that there has been an actual increase in the incidence of prosthetic joint infections after THA....

  12. Public Perception of Strategies for Increasing Participation in Recycling Programs. (United States)

    Nyamwange, Monica


    Assesses public perception of selected strategies for increasing participation in city recycling programs: increasing the level of knowledge about recycling, using effective channels to inform the community about recycling, increasing the convenience of recycling by placing recycling containers in accessible locations, and getting input from the…

  13. Increasing Labour Productivity in Agriculture and its Implications

    NARCIS (Netherlands)

    Ban, van den A.W.


    In order to profit from the economic growth in their society farmers can (1) increase the yields of their crops and animals, (2) switch to the production of high value products for which there is an increasing demand in the market, (3) increase the labour productivity on their farm, (4) find non-far

  14. Increased Sorting and Wage Inequality in the Czech Republic

    DEFF Research Database (Denmark)

    Eriksson, Tor Viking; Pytlikova, Mariola; Warzynski, Frederic

    and find evidence of slightly increasing returns to human capital and diminishing gender inequality. We then document sharp increases in both within-firm and between-firm inequality. We investigate various hypotheses to explain these patterns: increased domestic and international competition...... changes in wage inequality....

  15. Increasing portion sizes of fruits and vegetables in an elementary school lunch program can increase fruit and vegetable consumption. (United States)

    Miller, Nicole; Reicks, Marla; Redden, Joseph P; Mann, Traci; Mykerezi, Elton; Vickers, Zata


    Increasing portion size can increase children's consumption of food. The goal of this study was to determine whether increasing the portion sizes of fruits and vegetables in an elementary school cafeteria environment would increase children's consumption of them. We measured each child's consumption of the fruit and vegetables served in a cafeteria line on a control day (normal cafeteria procedures) and on two intervention days. When we increased the portion size of 3 of the 4 fruits and vegetables by about 50%, children who took those foods increased their consumption of them. Although this was an effective strategy for increasing fruit and vegetable consumption among students who took those foods, many children chose not to take any fruits or vegetables. Further efforts are needed to increase children's selection and consumption of fruits and vegetables in an environment of competing foods of higher palatability.

  16. Bullying increased suicide risk: prospective study of Korean adolescents. (United States)

    Kim, Young Shin; Leventhal, Bennett L; Koh, Yun-Joo; Boyce, W Thomas


    This study examines the independent impact of bullying on suicide risk. Bullying was assessed by peer nomination in a prospective study of 1,655 7th and 8th grade Korean students, and suicide by youth self-report. Odds Ratios (ORs) of bullying for suicidal risks were computed, controlling for other suicide risk factors. Victim-Perpetrators and female Victims at baseline showed increased risk for persistent suicidality (OR: 2.4-9.8). Male Incident Victims exhibited increased risk for suicidal behaviors and ideations (OR = 4.4, 3.6). Female Persistent Perpetrators exhibited increased risks for suicidal behaviors; male Incident Perpetrators had increased risk for suicidal ideations (OR = 2.7, 2.3). Baseline-only male Victim-Perpetrators showed increased risk for suicidal ideations. (OR = 6.4). Bullying independently increased suicide risks.

  17. Increased Sorting and Wage Inequality in the Czech Republic

    DEFF Research Database (Denmark)

    Eriksson, Tor; Pytlikova, Mariola; Warzynski, Frederic Michel Patrick


    This paper makes use of a linked employer–employee dataset to examine the evolution of wage inequality in the Czech Republic during 1998–2006. We find evidence of slightly increasing returns to human capital and diminishing gender inequality and document sharp increases in both within......-firm and between-firm inequality. We investigate several hypotheses to explain these patterns: increased domestic and international competition, decentralized wage bargaining, skill-biased technological change and a changing educational composition of the workforce. Domestic competition is found to lower within......-firm inequality whereas we find no evidence that increased international trade at the industry level is associated with higher betweenor within-firm wage inequality. The key factors driving the observed increase in wage inequality are increased educational sorting and the inflow of foreign firms to the Czech...

  18. Increasing thermal efficiency of solar flat plate collectors (United States)

    Pona, J.

    A study of methods to increase the efficiency of heat transfer in flat plate solar collectors is presented. In order to increase the heat transfer from the absorber plate to the working fluid inside the tubes, turbulent flow was induced by installing baffles within the tubes. The installation of the baffles resulted in a 7 to 12% increase in collector efficiency. Experiments were run on both 1 sq ft and 2 sq ft collectors each fitted with either slotted baffles or tubular baffles. A computer program was run comparing the baffled collector to the standard collector. The results obtained from the computer show that the baffled collectors have a 2.7% increase in life cycle cost (LCC) savings and a 3.6% increase in net cash flow for use in domestic hot water systems, and even greater increases when used in solar heating systems.

  19. Effect of Increasing Nitrogen Deposition on Soil Microbial Communities



    Increasing nitrogen deposition, increasing atmospheric CO2, and decreasing biodiversity are three main environmental changes occurring on a global scale. The BioCON (Biodiversity, CO2, and Nitrogen) ecological experiment site at the University of Minnesota's Cedar Creek Ecosystem Science Reserve started in 1997, to better understand how these changes would affect soil systems. To understand how increasing nitrogen deposition affects the microbial community diversity, heterogeneity, and functi...

  20. Clinical considerations for increasing occlusal vertical dimension: a review. (United States)

    Abduo, J; Lyons, K


    The purpose of this article is to discuss the clinical considerations related to increasing the occlusal vertical dimension (OVD) when restoring a patient's dentition. Thorough extraoral and intraoral evaluations are mandatory to assess the suitability of increasing OVD. In the literature, multiple techniques have been proposed to quantify OVD loss. However, the techniques lack consistency and reliability, which in turn affects the decision of whether to increase the OVD. Therefore, increasing OVD should be determined on the basis of the dental restorative needs and aesthetic demands. In general, a minimal increase in OVD should be applied, though a 5 mm maximum increase in OVD can be justified to provide adequate occlusal space for the restorative material and to improve anterior teeth aesthetics. The literature reflects the safety of increasing the OVD permanently, and although signs and symptoms may develop, these are usually of an interim nature. Whenever indicated, the increase in OVD should be achieved with fixed restorations rather than a removable appliance, due to the predictable patient adaptation. The exception to this is for patients with TMD, where increasing the OVD should still be achieved using removable appliances to control TMD-associated symptoms before considering any form of irreversible procedure.

  1. Increased thrombin generation in women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Sidelmann, Johannes Jakobsen; Lambaa Altinok, Magda


    Objective. Polycystic ovary syndrome (PCOS) is associated with risk factors for cardiovascular disease (CVD) which may be modified by the use of metformin and oral contraceptives (OC). Thrombin generation (TG) measures are risk markers of CVD and address the composite of multiple factors...... adjustment for these potential confounders. Treatment with OC and metformin +OC further increased ETP (Paffect TG...... significantly. Conclusions. PCOS is associated with increase in TG measures independent of other risk factors of CVD. OC increases TG measures further and may thus add to the increased risk of CVD already present in women with PCOS....

  2. Feeling entitled to more: ostracism increases dishonest behavior. (United States)

    Poon, Kai-Tak; Chen, Zhansheng; Dewall, C Nathan


    Five experiments tested whether ostracism increases dishonesty through increased feelings of entitlement. Compared with included and control participants, ostracized participants indicated higher levels of dishonest intentions (Experiments 1-3) and cheated more to take undeserved money in a behavioral task (Experiments 4 and 5). In addition, increased feelings of entitlement mediated the effect of ostracism on dishonesty (Experiments 3-5). Framing ostracism as beneficial weakened the connection between ostracism, entitlement, and dishonest behavior (Experiment 5). Together, these findings highlight the significance of entitlement in explaining when and why ostracism increases dishonest behavior and how to weaken this relationship.

  3. Warming rather than increased precipitation increases soil recalcitrant organic carbon in a semiarid grassland after 6 years of treatments.

    Directory of Open Access Journals (Sweden)

    Xiaoqi Zhou

    Full Text Available Improved understanding of changes in soil recalcitrant organic carbon (C in response to global warming is critical for predicting changes in soil organic C (SOC storage. Here, we took advantage of a long-term field experiment with increased temperature and precipitation to investigate the effects of warming, increased precipitation and their interactions on SOC fraction in a semiarid Inner Mongolian grassland of northern China since April 2005. We quantified labile SOC, recalcitrant SOC and stable SOC at 0-10 and 10-20 cm depths. Results showed that neither warming nor increased precipitation affected total SOC and stable SOC at either depth. Increased precipitation significantly increased labile SOC at the 0-10 cm depth. Warming decreased labile SOC (P = 0.038 and marginally but significantly increased recalcitrant SOC at the 10-20 cm depth (P = 0.082. In addition, there were significant interactive effects of warming and increased precipitation on labile SOC and recalcitrant SOC at the 0-10 cm depth (both P<0.05, indicating that that results from single factor experiments should be treated with caution because of multi-factor interactions. Given that the absolute increase of SOC in the recalcitrant SOC pool was much greater than the decrease in labile SOC, and that the mean residence time of recalcitrant SOC is much greater, our results suggest that soil C storage at 10-20 cm depth may increase with increasing temperature in this semiarid grassland.

  4. 75 FR 81003 - Rate Increase Disclosure and Review (United States)


    ... an alternative approach that is consistent with the language of section 2794; is more narrowly... trend increases. HHS reviewed available data and literature on insurance rate increases in States and... above, many States have these provisions today. The second factor is whether the State...

  5. Airway smooth muscle cell proliferation is increased in asthma

    NARCIS (Netherlands)

    Johnson, P R; Roth, Michael; Tamm, M; Hughes, J Margaret; Ge, Q; King, G; Burgess, J K; Black, J L


    UNLABELLED: Increased airway smooth muscle (ASM) within the bronchial wall of asthmatic patients has been well documented and is likely to be the result of increased muscle proliferation. We have for the first time been able to culture ASM cells from asthmatic patients and to compare their prolifera

  6. The Older Woman: Increased Psychosocial Benefits from Physical Activity. (United States)

    Wakat, Diane; Odom, Sarah


    Older women who participate in physical activity programs find physical benefits in the improvement of cardiovascular and musculoskeletal systems. The psychosocial benefits which result from physical activity include an increase in self-esteem, increased social contacts, a counteraction to depression, and improved stress management. Suggestions…

  7. Elevated cAMP increases aquaporin-3 plasma membrane diffusion

    DEFF Research Database (Denmark)

    Marlar, Saw; Christensen, Eva Arnspang; Koffman, Jennifer Skaarup


    .05)]. Immunoelectron microscopy showed no obvious difference in AQP3-EGFP expression levels or localization in the plasma membrane upon forskolin stimulation. Thus AQP3-EGFP diffusion is altered upon increased cAMP, which may correspond to basolateral adaptations in response to the increased apical water readsorption...

  8. Nontraditional Student Engagement: Increasing Adult Student Success and Retention (United States)

    Wyatt, Linda G.


    Today, more than any other time in history, student demographics of college and university students in the United States are experiencing rapid and profound changes. Along with these increases in nontraditional student enrollment comes an increasing percentage of working nontraditional college students with a multitude of commitments that serve to…

  9. Pollution prevention: increasing environmental capabilities of SMEs through collaboration

    NARCIS (Netherlands)

    Bruijn, de Theo; Hofman, Peter S.; Bruijn, de Theo J.N.M.; Tukker, Arnold


    The concept of sustainability increasingly impacts the nature of industry’s operations. Whereas in the past sound economic performance was expected to guarantee success by companies and its shareholders, now increasingly business is led by the so-called triple bottom line. Achieving good economic re

  10. 21 CFR 1303.25 - Increase in individual manufacturing quotas. (United States)


    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Increase in individual manufacturing quotas. 1303... Individual Manufacturing Quotas § 1303.25 Increase in individual manufacturing quotas. (a) Any registrant who holds an individual manufacturing quota for a basic class of controlled substance listed in Schedule...

  11. 21 CFR 1315.25 - Increase in individual manufacturing quotas. (United States)


    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Increase in individual manufacturing quotas. 1315... AND PRODUCTION QUOTAS FOR EPHEDRINE, PSEUDOEPHEDRINE, AND PHENYLPROPANOLAMINE Individual Manufacturing Quotas § 1315.25 Increase in individual manufacturing quotas. (a) Any registrant who holds an...

  12. Community and ecosystem ramifications of increasing lianas in neotropical forests

    NARCIS (Netherlands)

    Schnitzer, S.A.; Bongers, F.; Wright, J.


    Lianas (woody vines) are increasing in neotropical forests, representing one of the first large-scale structural changes documented for these important ecosystems. The potential ramifications of increasing lianas are huge, as lianas alter both tropical forest diversity and ecosystem functioning. At

  13. Association Between Increased Waist Circumference and Depression and Anxiety Trend

    Directory of Open Access Journals (Sweden)

    Elena Bocicor Andreea


    Full Text Available Introduction: Abdominal adiposity assessed by increased waist circumference and depression have both a high incidence and prevalence and are associated with increased general mortality and cardiovascular risk. Several studies showed a significant association between abdominal obesity, metabolic syndrome and depression. Early detection of these associations is important for for prevention and treatment of this disease.

  14. Increasing self-drinking for children with feeding disorders. (United States)

    Peterson, Kathryn M; Volkert, Valerie M; Zeleny, Jason R


    Children with feeding disorders often do not self-drink without treatment. Unfortunately, the literature on self-drinking is scarce. We evaluated differential positive reinforcement to increase self-drinking for 2 children with feeding disorders. Results showed that differential positive reinforcement with tangible items increased self-drinking for both children in the absence of nonremoval of the cup.

  15. 5 CFR 837.603 - Increased survivor benefits. (United States)


    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Increased survivor benefits. 837.603... REGULATIONS (CONTINUED) REEMPLOYMENT OF ANNUITANTS Death Benefits § 837.603 Increased survivor benefits. (a) Supplemental survivor annuity. (1) If an annuitant reemployed subject to the provisions of this part dies...

  16. A Flipped Spoon and Chin Prompt to Increase Mouth Clean (United States)

    Dempsey, Jack; Piazza, Cathleen C.; Groff, Rebecca A.; Kozisek, Jennifer M.


    We treated the liquid refusal of a 15-month-old girl using 2 antecedent manipulations: flipped spoon and chin prompt. Use of the chin prompt in the absence of the flipped spoon failed to produce increases in mouth clean (a product measure of swallowing). By contrast, modest increases in mouth clean resulted from the implementation of the flipped…

  17. China's success in increasing per capita food production. (United States)

    Zhang, Jianhua


    China has to feed 20% of the global population with only about 5% of the planet's water resources and 7% of its arable land. With such limited natural conditions, however, China's grain production has increased from about 200 kg per capita in 1949 to about 400 kg in the early 1990s. Hunger as a social problem has largely disappeared after being prevalent in China for several thousand years with the rise and decline of dynasties. This achievement has been accompanied by a 2.5-fold increase in the population and a 4.5-fold increase in total grain production. Although total cropped land has increased slightly in some areas, land used for cropping has decreased from 0.18 hectare per capita in the 1950s to less than 0.1 hectare per capita today. Apparently, yield increase or improved land productivity is the major contributor to the increase of food production per capita. What are the major reasons for the unprecedented achievement in China's food production? Political decisions, good or bad, on land distribution and ownership changes, have caused unusual fluctuation in grain production. Technical progress, however, has maintained a long-term increasing trend. The semi-dwarf cultivars of rice and wheat, the use of heterosis in rice and maize, and the alleviation of salinized soil stress in the major grain-producing areas have all played significant roles in increasing China's food production capability.

  18. 76 FR 67320 - Walnuts Grown in California; Increased Assessment Rate (United States)


    ..., these costs are offset by the benefits derived by the operation of the marketing order. In addition, the... Agricultural Marketing Service 7 CFR Part 984 Walnuts Grown in California; Increased Assessment Rate AGENCY: Agricultural Marketing Service, USDA. ACTION: Final rule. SUMMARY: This rule increases the assessment...

  19. How to Determine the Increasing Returns Sensitivity of Your Industry?

    NARCIS (Netherlands)

    M.H. Klein (Martin); E. den Hartigh; H.R. Commandeur (Harry); F. Langerak (Fred)


    textabstractIncreasing returns means that self-reinforcing mechanisms are at work within firms and markets. These mechanisms come in four forms: scale effects, learning effects, network effects and social interaction effects. Some industries are more sensitive to increasing returns than others. It i

  20. Designing Experiences to Increase Stadium Capacity Utilisation in Football

    DEFF Research Database (Denmark)

    Junghagen, Sven; Besjakov, Simon D; Lund, Anders Alrø


    The aim of this paper is to show in what way football clubs in smaller leagues with limited capacity utilisation can increase their per-game revenue by increasing the attendance frequency. A sequential mixed method research design was employed, involving both qualitative and quantitative methods...