Sample records for human apo a-i

  1. ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer (United States)

    Cedó, Lídia; García-León, Annabel; Baila-Rueda, Lucía; Santos, David; Grijalva, Victor; Martínez-Cignoni, Melanie Raquel; Carbó, José M.; Metso, Jari; López-Vilaró, Laura; Zorzano, Antonio; Valledor, Annabel F.; Cenarro, Ana; Jauhiainen, Matti; Lerma, Enrique; Fogelman, Alan M.; Reddy, Srinivasa T.; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco


    Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification. PMID:27808249

  2. HDL-apoA-I Exchange: Rapid Detection and Association with Atherosclerosis (United States)

    Borja, Mark S.; Zhao, Lei; Hammerson, Bradley; Tang, Chongren; Yang, Richard; Carson, Nancy; Fernando, Gayani; Liu, Xiaoqin; Budamagunta, Madhu S.; Genest, Jacques; Shearer, Gregory C.; Duclos, Franck; Oda, Michael N.


    High density lipoprotein (HDL) cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR) to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease. PMID:24015188

  3. HDL-apoA-I exchange: rapid detection and association with atherosclerosis.

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    Mark S Borja

    Full Text Available High density lipoprotein (HDL cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease.

  4. High serum apolipoprotein E determines hypertriglyceridemic dyslipidemias, coronary disease and apoA-I dysfunctionality. (United States)

    Onat, Altan; Can, Günay; Ornek, Ender; Ayhan, Erkan; Erginel-Ünaltuna, Nihan; Murat, Sani N


    The relevance of serum apolipoprotein E (apoE) levels to two hypertriglyceridemic dyslipidemias has not been clarified. We explored, in a cross-sectional (and short-term prospective) evaluation, the independent relationship of serum apoE to the atherogenic dyslipidemia, hypertriglyceridemia with elevated apoB (HtgB) and to apoA-I dysfunctionality, previously shown in Turkish adults to be independent of apoE genotype. Serum apoE concentrations were measured by immunonephelometry in 1,127 middle-aged adults. In multivariable regression analysis, apoE concentrations showed log-linear associations with apoB and apoA-I levels, waist circumference, independent of C-reactive protein (CRP), homeostatic model assessment (HOMA) index and other confounders. The likelihood of atherogenic dyslipidemia and of HtgB roughly tripled per 1-SD increment in apoE concentrations, additively to apoE genotype, HOMA, apoA-I, CRP concentrations and waist circumference; yet apoA-I, protective against atherogenic dyslipidemia, appeared to promote HtgB, a finding consistent with apoA-I dysfunctionality in this setting. Each 1-SD increment in the apoE level was moreover, associated in both genders with MetS (at OR 1.5), after adjustment for sex, age, apoB, apoA-I and CRP, or for apoE genotypes. Circulating apoE predicted in both genders age-adjusted prevalent and incident coronary heart disease (CHD), independent of apoE genotype and CRP (OR 1.32 [95 % CI 1.11; 1.58]). To conclude, in a general population prone to MetS, elevated apoE concentrations are strongly linked to HtgB and atherogenic dyslipidemia, irrespective of apoE genotype, are associated with MetS and CHD. Excess apoE reflects pro-inflammatory state and likely autoimmune activation.

  5. Dysfunctional HDL containing L159R apoA-I leads to exacerbation of atherosclerosis in hyperlipidemic mice (United States)

    In this study, the effect of the mutation L159R apoA-I or apoA-IL159R (FIN) was assessed. apoA-IL159R (FIN) is associated with a dominant negative phenotype, displaying hypoalphaproteinemia and an increased risk for atherosclerosis in humans. Transgenic mice lines were created through strategic mati...

  6. Effect of macrophage-derived mouse ApoE, human ApoE3-Leiden, and human ApoE2 (Arg158→Cys) on cholesterol levels and atherosclerosis in ApoE- deficient mice

    NARCIS (Netherlands)

    Eck, M. van; Herijgers, N.; Dijk, K.W. van; Havekes, L.M.; Hofker, M.H.; Groot, P.H.E.; Berkel, T.J.C. van


    The effect of monocyte/macrophage-derived wild-type mouse apolipoprotein E (apoE), human apoE3-Leiden, and human apoE2 on serum cholesterol levels and the development of atherosclerosis in apoE-deficient (apoe-/-) mice was investigated by using bone marrow transplantation (BMT). At 4 weeks after

  7. Effect of treatment with human apolipoprotein A-I on atherosclerosis in uremic apolipoprotein-E deficient mice

    DEFF Research Database (Denmark)

    Pedersen, Tanja Xenia; Bro, Susanne; Andersen, Mikkel H


    OBJECTIVE: Uremia markedly increases the risk of atherosclerosis. Thus, effective anti-atherogenic treatments are needed for uremic patients. This study examined effects of non-lipidated recombinant human apoA-I (h-apoA-I) and a recombinant trimeric apoA-I molecule (TripA-I) on lipid metabolism a...

  8. The human apoE7 and apoE4 transgenic mice models

    Institute of Scientific and Technical Information of China (English)

    孙明增; 琦祖和


    To scrutinize the disorders caused by human mutant apoE7/apoE4, human apoE4 and E7 transgenic mice were established with microinjection technique to examine molecular genetic phenomena in vivo. The integration and expression of h-apoE mutant genes in transgenic mice were determined with Southern blot, Northern blot and ELISA. The current studies indicated that the transgenes and the phenotypes regarding expression of transgenes could be transmitted stably in transgenic lines. The levels of serum lipid in transgenic mice showed the characteristics of hyperlipidemia. Besides, behavior tests demonstrated the degeneration of learning and memory in transgenic mice. Short life span was observed in 2 transgenic lines. After fed with high lipid food high serum lipid was found both in normal and transgenic mice, but their mechanism regulating lipid metabolism was different. It was also verified that the human apoE mutants located at either N-terminal or C-terminal had the same pathogenesis regarding disorders of lipid metabolism in murine.

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

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    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.

  10. Effect of TNF{alpha} on activities of different promoters of human apolipoprotein A-I gene

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    Orlov, Sergey V., E-mail: [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Mogilenko, Denis A. [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Shavva, Vladimir S. [Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Dizhe, Ella B.; Ignatovich, Irina A. [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Perevozchikov, Andrej P., E-mail: [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation)


    Research highlights: {yields} TNF{alpha} stimulates the distal alternative promoter of human apoA-I gene. {yields} TNF{alpha} acts by weakening of promoter competition within apoA-I gene (promoter switching). {yields} MEK1/2 and nuclear receptors PPAR{alpha} and LXRs take part in apoA-I promoter switching. -- Abstract: Human apolipoprotein A-I (ApoA-I) is a major structural and functional protein component of high-density lipoproteins. The expression of the apolipoprotein A-I gene (apoA-I) in hepatocytes is repressed by pro-inflammatory cytokines such as IL-1{beta} and TNF{alpha}. Recently, two novel additional (alternative) promoters for human apoA-I gene have been identified. Nothing is known about the role of alternative promoters in TNF{alpha}-mediated downregulation of apoA-I gene. In this article we report for the first time about the different effects of TNF{alpha} on two alternative promoters of human apoA-I gene. Stimulation of HepG2 cells by TNF{alpha} leads to activation of the distal alternative apoA-I promoter and downregulation of the proximal alternative and the canonical apoA-I promoters. This effect is mediated by weakening of the promoter competition within human apoA-I 5'-regulatory region (apoA-I promoter switching) in the cells treated by TNF{alpha}. The MEK1/2-ERK1/2 cascade and nuclear receptors PPAR{alpha} and LXRs are important for TNF{alpha}-mediated apoA-I promoter switching.

  11. 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.

  12. Introducing Human APOE into Aβ Transgenic Mouse Models

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    Leon M. Tai


    Full Text Available Apolipoprotein E (apoE and apoE/amyloid-β (Aβ transgenic (Tg mouse models are critical to understanding apoE-isoform effects on Alzheimer's disease risk. Compared to wild type, apoE−/− mice exhibit neuronal deficits, similar to apoE4-Tg compared to apoE3-Tg mice, providing a model for Aβ-independent apoE effects on neurodegeneration. To determine the effects of apoE on Aβ-induced neuropathology, apoE−/− mice were crossed with Aβ-Tg mice, resulting in a significant delay in plaque deposition. Surprisingly, crossing human-apoE-Tg mice with apoE−/−/Aβ-Tg mice further delayed plaque deposition, which eventually developed in apoE4/Aβ-Tg mice prior to apoE3/Aβ-Tg. One approach to address hAPOE-induced temporal delay in Aβ pathology is an additional insult, like head injury. Another is crossing human-apoE-Tg mice with Aβ-Tg mice that have rapid-onset Aβ pathology. For example, because 5xFAD mice develop plaques by 2 months, the prediction is that human-apoE/5xFAD-Tg mice develop plaques around 6 months and 12 months before other human-apoE/Aβ-Tg mice. Thus, tractable models for human-apoE/Aβ-Tg mice continue to evolve.

  13. Apolipoprotein A-I inhibits LPS-induced atherosclerosis in ApoE-/-mice possibly via activated STAT3-mediated upregulation of tristetraprolin

    Institute of Scientific and Technical Information of China (English)

    Kai YIN; Shi-lin TANG; Xiao-hua YU; Guang-hui TU; Rong-fang HE; Jin-feng LI; Di XIE


    Aim:To investigate the effects of the major component of high-density lipoprotein apolipoprotein A-I (apoA-I) on the development of atherosclerosis in LPS-challenged ApoE-/-mice and the underlying mechanisms.Methods:Male ApoE-KO mice were daily injected with LPS (25 μg,sc) or PBS for 4 weeks.The LPS-challenged mice were intravenously injected with rAAV-apoA-I-GFP or rAAV-GFP.After the animals were killed,blood,livers and aortas were collected for biochemical and histological analyses.For ex vivo experiments,the abdominal cavity macrophages were harvested from each treatment group of mice,and cultured with autologous serum,then treated with LPS.Results:Chronic administration of LPS in ApoE-/-mice significantly increased the expression of inflammatory cytokines (TNF-α,IL-1β,IL-6,and MCP-1),increased infiltration of inflammatory cells,and enhanced the development of atherosclerosis.In LPS-challenged mice injected with rAAV-apoA-I-GFP,viral particles and human apoA-I were detected in the livers,total plasma human apoA-I levels were grammatically increased; HDL-cholesterol level was significantly increased,TG and TC were slightly increased.Furthermore,overexpression of apoA-l significantly suppressed the expression of proinflammatory cytokines,reduced the infiltration of inflammatory cells,and decreased the extent of atherosclerotic lesions.Moreover,overexpression of apoA-I significantly increased the expression of the cytokine mRNA-destabilizing protein tristetraprolin (TTP),and phosphorylation of JAK2 and STAT3 in aortas.In ex vivo mouse macrophages,the serum from mice overexpressing apoA-I significantly increased the expression of TTP,accompanied by accelerated decay of mRNAs of the inflammatory cytokines.Conclusion:ApoA-I potently suppresses LPS-induced atherosclerosis by inhibiting the inflammatory response possibly via activation of STAT3 and upregulation of TTP.

  14. A facile method for isolation of recombinant human apolipoprotein A-I from E. coli. (United States)

    Ikon, Nikita; Shearer, Jennifer; Liu, Jianfang; Tran, Jesse J; Feng, ShiBo; Kamei, Ayako; Beckstead, Jennifer A; Kiss, Robert S; Weers, Paul M; Ren, Gang; Ryan, Robert O


    Apolipoprotein (apo) A-I is the major protein component of high-density lipoprotein (HDL) and plays key roles in the Reverse Cholesterol Transport pathway. In the past decade, reconstituted HDL (rHDL) has been employed as a therapeutic agent for treatment of atherosclerosis. The ability of rHDL to promote cholesterol efflux from peripheral cells has been documented to reduce the size of atherosclerotic plaque lesions. However, development of apoA-I rHDL-based therapeutics for human use requires a cost effective process to generate an apoA-I product that meets "Good Manufacturing Practice" standards. Methods available for production and isolation of unmodified recombinant human apoA-I at scale are cumbersome, laborious and complex. To overcome this obstacle, a streamlined two-step procedure has been devised for isolation of recombinant untagged human apoA-I from E. coli that takes advantage of its ability to re-fold to a native conformation following denaturation. Heat treatment of a sonicated E. coli supernatant fraction induced precipitation of a large proportion of host cell proteins (HCP), yielding apoA-I as the major soluble protein. Reversed-phase HPLC of this material permitted recovery of apoA-I largely free of HCP and endotoxin. Purified apoA-I possessed α-helix secondary structure, formed rHDL upon incubation with phospholipid and efficiently promoted cholesterol efflux from cholesterol loaded J774 macrophages.

  15. Automation of PRM-dependent D3-Leu tracer enrichment in HDL to study the metabolism of apoA-I, LCAT and other apolipoproteins. (United States)

    Lee, Lang Ho; Andraski, Allison B; Pieper, Brett; Higashi, Hideyuki; Sacks, Frank M; Aikawa, Masanori; Singh, Sasha A


    We developed an automated quantification workflow for PRM-enabled detection of D3-Leu labeled apoA-I in high-density lipoprotein (HDL) isolated from humans. Subjects received a bolus injection of D3-Leu and blood was drawn at eight time points over three days. HDL was isolated and separated into six size fractions for subsequent proteolysis and PRM analysis for the detection of D3-Leu signal from ∼0.03 to 0.6% enrichment. We implemented an intensity-based quantification approach that takes advantage of high-resolution/accurate mass PRM scans to identify the D3-Leu 2HM3 ion from non-specific peaks. Our workflow includes five modules for extracting the targeted PRM peak intensities (XPIs): Peak centroiding, noise removal, fragment ion matching using Δm/z windows, nine intensity quantification options, and validation and visualization outputs. We optimized the XPI workflow using in vitro synthesized and clinical samples of D0/D3-Leu labeled apoA-I. Three subjects' apoA-I enrichment curves in six HDL size fractions, and LCAT, apoA-II and apoE from two size fractions were generated within a few hours. Our PRM strategy and automated quantification workflow will expedite the turnaround of HDL apoA-I metabolism data in clinical studies that aim to understand and treat the mechanisms behind dyslipidemia.

  16. Altered neurotransmission in the lateral amygdala in aged human apoE4 targeted replacement mice. (United States)

    Klein, Rebecca C; Acheson, Shawn K; Mace, Brian E; Sullivan, Patrick M; Moore, Scott D


    The human APOE4 allele is associated with an early age of onset and increased risk of Alzheimer's disease (AD). Apolipoprotein E is secreted as part of a high-density lipoprotein-like particle by glial cells in the brain for the primary purpose of transport of lipophilic compounds involved in the maintenance of synapses. Previous studies examining synaptic integrity in the amygdala of human apoE targeted replacement (TR) mice showed a decrease in spontaneous excitatory synaptic activity, dendritic arbor, and spine density associated with apoE4 compared with apoE3 and apoE2 in adult male mice. In the present study, we assessed how APOE genotype affects synaptic integrity of amygdala neurons by comparing electrophysiological and morphometric properties in human apoE3, E4, and E2/4 TR mice at the age of 18-20 months. In contrast to adult mice, we found that aged apoE4 TR mice exhibited the highest level of excitatory synaptic activity compared with other cohorts. Additionally, apoE4 mice had significantly greater spontaneous inhibitory activity than all other cohorts. Taken together, there was a significant interaction between genotypes when comparing inhibition relative to excitation; there was a simple main effect of frequency type with an imbalance toward inhibition in apoE4 mice but not in apoE3 or apoE2/4 mice. These results suggest that apoE isoforms differentially influence synaptic transmission throughout the life span, where aging coupled with apoE4 expression, results in an imbalance in maintaining integrity of synaptic transmission.

  17. [Separation and purification of human apolipoproteins A-I and C-III by chromatofocusing]. (United States)

    Cheng, B


    Human very low density lipoprotein (VLDL) and high density lipoprotein (HDL) were isolated and purified by a process of combined dextran sulfate precipitation and density gradient ultracentrifugation. Chromatofocusing, which separates protein based on differences in isoelectric point, was used to separate apolipoprotein A-I (apoA-I) and apolipoprotein C-III from human HDL and VLDL, respectively. Discontinuous SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and analytical isoelectric focusing (IEF) were used to study the purity of different fractions. Both purified apoA-I and apoC-III showed single bands on SDS-PAGE at molecular weights of 28183 and 9400 Daltons, respectively. As determined by IEF in the presence of 8 mol/L urea, apoA-I had eight isoforms with pI of 5.66-5.87. The pI's of the three isoproteins of apoC-III (C-III0, C-III1 and C-III2) were 5.06, 4.88 and 4.72, respectively. Chromatofocusing, a new simple technique combining the high resolving power of IEF with the high capacity of ion-exchange column chromatography, is extremely valuable for large-scale purification of the major apolipoproteins of VLDL and HDL.

  18. ApoA-I mutations, L202P and K131del, in HDL from heterozygotes with low HDL-C

    NARCIS (Netherlands)

    Ljunggren, Stefan; Levels, Johannes H. M.; Turkina, Maria V.; Sundberg, Sofie; Bochem, Andrea E.; Hovingh, Kees; Holleboom, Adriaan G.; Lindahl, Mats; Kuivenhoven, Jan Albert; Karlsson, Helen

    PurposeMutations in apolipoprotein A-I (apoA-I) may affect plasma high-density lipoprotein (HDL) cholesterol levels and the risk for cardiovascular disease but little is known about the presence and effects of circulating apoA-I variants. This study investigates whether the apoA-I mutations,

  19. Characterization of human high-density lipoprotein subclasses LP A-I and LP A-I/A-II and binding to HepG2 cells

    NARCIS (Netherlands)

    E.P.C. Kilsdonk (Liesbeth); T. van Gent (Teus); A. van Tol (Arie)


    markdownabstractAbstract Plasma HDL can be classified according to their apolipoprotein content into at least two types of lipoprotein particles: lipoproteins containing both apo A-I and apo A-II (LP A-I/A-II) and lipoproteins with apo A-I but without apo A-II (LP A-I). LP A-I and LP A-I/A-II

  20. The human apoE7 and apoE4 transgenic mice models

    Institute of Scientific and Technical Information of China (English)

    SUN; Mingzeng; (


    [1]Weisgraber, K. H., Apolipoprotein E: Structure-function relationships, Adv. Pro. Chem., 1994, 45: 249-302.[2]Center, G. F., Paoletti, E. G., Apolipoprotein function in health and disease: Insights from natural mutations, Europ. J. Clin. Invest., 1996, 26: 733-746.[3]Browner, J. D., van Dormal, J. J., Muskiet, A. J., Clinical chemistry of common apolipoproteins, J. Chromat. B, 1996, 678: 623-641.[4]Maeda, H., Nakamura, H., Shozo, K. et al., Identification of human apolipoprotein E variant gene: Apolipoprotein E7 (Glu244, 245 Lys244, 245), J. Biochm., 1989, 105: 51-54.[5]Taylor, J. M., Downstream regulatory elements stimulate expression of the human plipoprotein E gene in the liver and suppress expression in the kidney of transgenic mice, Transassoc. Am. Physicians, 1990, 103: 119-128.[6]Smith, J. D., Plump, A. S., Breslow, J. L. et al., Accumulation of human apolipoprotein E in the plasma of transgenic mice, J. Biol. Chem., 1990, 265(25): 14709-14712.[7]Tazio, S., Lee, Y. L., Ji, Z. S. et al., Type III hyperlipoproteinemic phenotype in transgenic mice expressing dysfunctional apolipoprotein E, J. Clin. Invest., 1993, 92(3): 1497-1503.[8]Arn, M. J., Maagdenberg, M., Hofker, M. N. et al., Transgenic mice carrying the apolipoprotein E3-Leiden gene exhibit hyperlipoproteinemia, The J. Biol. Chem., 1993, 268(14): 10540-10545.[9]Qi, Z. H., Ru, K., Sun, M. Z. et al., The gene expression of pME in mouse NIH/3T3 cells and construction of the h-apoE transgenic mice, Chinese Biochem. J., 1997, 13(1): 24-28.[10]Sambrook, J., Fritsch, E. F., Maniatis, T., Molecular Cloning, A Laboratory Manual, New York: CSH Press, 1989, 81.[11]Hogan, B. L., Manipulation the mouse embryo, A Laboratory Manual, New York: CSH Press, 1989, 89.[12]Wandell, M. R., Rall, S. C., Brennan, S. Jr et al., Apolipoprotein E2-Dunedin (228 Arg-Cys): Anapolipoprotein E2 variant with normal receptor-binding activity, J. Lip. Res., 1990, 31: 534-543.[13

  1. Akt inhibition promotes ABCA1-mediated cholesterol efflux to ApoA-I through suppressing mTORC1.

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    Fumin Dong

    Full Text Available ATP-binding cassette transporter A1 (ABCA1 plays an essential role in mediating cholesterol efflux to apolipoprotein A-I (apoA-I, a major housekeeping mechanism for cellular cholesterol homeostasis. After initial engagement with ABCA1, apoA-I directly interacts with the plasma membrane to acquire cholesterol. This apoA-I lipidation process is also known to require cellular signaling processes, presumably to support cholesterol trafficking to the plasma membrane. We report here that one of major signaling pathways in mammalian cells, Akt, is also involved. In several cell models that express ABCA1 including macrophages, pancreatic beta cells and hepatocytes, inhibition of Akt increases cholesterol efflux to apoA-I. Importantly, Akt inhibition has little effect on cells expressing non-functional mutant of ABCA1, implicating a specific role of Akt in ABCA1 function. Furthermore, we provide evidence that mTORC1, a major downstream target of Akt, is also a negative regulator of cholesterol efflux. In cells where mTORC1 is constitutively activated due to tuberous sclerosis complex 2 deletion, cholesterol efflux to apoA-I is no longer sensitive to Akt activity. This suggests that Akt suppresses cholesterol efflux through mTORC1 activation. Indeed, inhibition of mTORC1 by rapamycin or Torin-1 promotes cholesterol efflux. On the other hand, autophagy, one of the major pathways of cholesterol trafficking, is increased upon Akt inhibition. Furthermore, Akt inhibition disrupts lipid rafts, which is known to promote cholesterol efflux to apoA-I. We therefore conclude that Akt, through its downstream targets, mTORC1 and hence autophagy, negatively regulates cholesterol efflux to apoA-I.

  2. Site-specific nitration of apolipoprotein A-I at tyrosine 166 is both abundant within human atherosclerotic plaque and dysfunctional. (United States)

    DiDonato, Joseph A; Aulak, Kulwant; Huang, Ying; Wagner, Matthew; Gerstenecker, Gary; Topbas, Celalettin; Gogonea, Valentin; DiDonato, Anthony J; Tang, W H Wilson; Mehl, Ryan A; Fox, Paul L; Plow, Edward F; Smith, Jonathan D; Fisher, Edward A; Hazen, Stanley L


    We reported previously that apolipoprotein A-I (apoA-I) is oxidatively modified in the artery wall at tyrosine 166 (Tyr(166)), serving as a preferred site for post-translational modification through nitration. Recent studies, however, question the extent and functional importance of apoA-I Tyr(166) nitration based upon studies of HDL-like particles recovered from atherosclerotic lesions. We developed a monoclonal antibody (mAb 4G11.2) that recognizes, in both free and HDL-bound forms, apoA-I harboring a 3-nitrotyrosine at position 166 apoA-I (NO2-Tyr(166)-apoA-I) to investigate the presence, distribution, and function of this modified apoA-I form in atherosclerotic and normal artery wall. We also developed recombinant apoA-I with site-specific 3-nitrotyrosine incorporation only at position 166 using an evolved orthogonal nitro-Tyr-aminoacyl-tRNA synthetase/tRNACUA pair for functional studies. Studies with mAb 4G11.2 showed that NO2-Tyr(166)-apoA-I was easily detected in atherosclerotic human coronary arteries and accounted for ∼ 8% of total apoA-I within the artery wall but was nearly undetectable (>100-fold less) in normal coronary arteries. Buoyant density ultracentrifugation analyses showed that NO2-Tyr(166)-apoA-I existed as a lipid-poor lipoprotein with nitration of apoA-I at Tyr(166) is an abundant modification within the artery wall that results in selective functional impairments. Plasma levels of this modified apoA-I form may provide insights into a pathophysiological process within the diseased artery wall.

  3. ApoA-I/HDL-C levels are inversely associated with abdominal aortic aneurysm progression

    DEFF Research Database (Denmark)

    Burillo, Elena; Lindholt, Jes S.; Molina-Sánchez, Pedro


    Abdominal aortic aneurysm (AAA) evolution is unpredictable, and there is no therapy except surgery for patients with an aortic size> 5 cm (large AAA). We aimed to identify new potential biomarkers that could facilitate prognosis and treatment of patients with AAA. A differential quantitative...... a negative correlation with aortic size (r=-0.4, paneurysmal growth rate in multiple linear regression analysis (n=122, p=0...... proteomic analysis of plasma proteins was performed in AAA patients at different stages of evolution [small AAA (aortic size=3-5 cm) vs large AAA] using iTRAQ labelling, high-throughput nano-LC-MS/MS and a novel multi-layered statistical model. Among the proteins identified, ApoA-I was decreased in patients...

  4. HDL-C / apoA-I ] : a multi-vessel cardiometabolic risk marker in women with T2DM. (United States)

    Hermans, Michel P; Valensi, Paul; Ahn, Sylvie A; Rousseau, Michel F


    Although women have higher HDL-C than men, their HDL particles are also prone to become small, dense and dysfunctional in case of T2DM. To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL-C to its main apolipoprotein (apoA-I), as [HDL-C/apoA-I]. This ratio estimates HDLs size and provides indices as to their number, cholesterol load, and density. We stratified 280 Caucasian T2DM women according to [HDL-C/apoA-I] quartiles (Q), to determine how it segregates cardiometabolic risk, β-cell function, glycemic control, and vascular complications. Five parameters were derived from combined determination of HDL-C and apoA-I : HDL size; HDL number; cholesterol load per particle (pP); apoA-IpP; and HDL density. An adverse cardiometabolic profile characterized Q-I and Q-II patients, whose HDLs were denser and apoA-I-depleted, whereas Q-III patients had HDLs with characteristics closer to controls. Q-IV patients had HDLs of supernormal size/composition and a more favorable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, β-cell function (32% vs 23%); exogenous insulin (44 vs 89 U/day), and glycemic control (HbA1c: 56 vs 61 mmol/mol), associated with lower prevalence of micro-/macrovascular complications: all-cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all-cause macroangiopathy 19% vs 31%; and CAD: 6% vs 24% (pHDL-C/apoA-I] can stratify T2DM women according to metabolic phenotype, macrovascular and coronary damage, β-cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women. This article is protected by copyright. All rights reserved.

  5. The Human Autoantibody Response to Apolipoprotein A-I Is Focused on the C-Terminal Helix: A New Rationale for Diagnosis and Treatment of Cardiovascular Disease?

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    Sabrina Pagano

    Full Text Available Cardiovascular disease (CVD is the leading cause of death worldwide and new approaches for both diagnosis and treatment are required. Autoantibodies directed against apolipoprotein A-I (ApoA-I represent promising biomarkers for use in risk stratification of CVD and may also play a direct role in pathogenesis.To characterize the anti-ApoA-I autoantibody response, we measured the immunoreactivity to engineered peptides corresponding to the different alpha-helical regions of ApoA-I, using plasma from acute chest pain cohort patients known to be positive for anti-ApoA-I autoantibodies.Our results indicate that the anti-ApoA-I autoantibody response is strongly biased towards the C-terminal alpha-helix of the protein, with an optimized mimetic peptide corresponding to this part of the protein recapitulating the diagnostic accuracy for an acute ischemic coronary etiology (non-ST segment elevation myocardial infarction and unstable angina obtainable using intact endogenous ApoA-I in immunoassay. Furthermore, the optimized mimetic peptide strongly inhibits the pathology-associated capacity of anti-ApoA-I antibodies to elicit proinflammatory cytokine release from cultured human macrophages.In addition to providing a rationale for the development of new approaches for the diagnosis and therapy of CVD, our observations may contribute to the elucidation of how anti-ApoA-I autoantibodies are elicited in individuals without autoimmune disease.

  6. ApoM/HDL-C and apoM/apoA-I ratios are indicators of diabetic nephropathy in healthy controls and type 2 diabetes mellitus. (United States)

    Zhang, Puhong; Gao, Jialin; Pu, Chun; Feng, Gang; Wang, Lizhuo; Huang, Lizhu; Zhang, Yao


    Apolipoprotein M (apoM) concentrations were decreased in type 2 diabetes mellitus (T2DM). ApoM was selectively expressed in renal tubular epithelial cells. We investigated the changes in plasma apoM concentrations in diabetic nephropathy (DN) patients and the potential of apoM as a biomarker of DN. A total of 96 DN patients and 100 age- and sex-matched diabetic non-nephropathy (non-DN) patients and 110 healthy controls were included. All T2DM patients were divided into 3 groups according to urinary albumin excretion: normoalbuminuria (n=100), microalbuminuria (n=50) and macroalbuminuria (n=46). Plasma apoM concentrations were measured by enzyme-linked immunosorbent assay. DN Patients had higher plasma apoM concentrations than those in non-DN patients (22.23±11.69 vs. 18.96±7.85ng/μl, PHDL-C and apoM/apoA1 than those in healthy controls and in non-DN patients. ApoM/HDL-C and apoM/apoA1 ratios could be used as indicators for identification of DN from healthy people (AUC=0.597, P=0.016; AUC=0.665, P=0.000, respectively) and from T2DM (AUC=0.580, P=0.050; AUC=0.601, P=0.015, respectively). ApoM/HDL-C and apoM/apoA1 ratios could be used as indicators for identification of DN from healthy people and from T2DM patients. Copyright © 2017. Published by Elsevier B.V.

  7. Expression of Lecithin: Cholesterol Acyltransferaseand/or apoA-I Mediated by Recombinant Adeno-as-sociated Virus in Myogenic Cell

    Institute of Scientific and Technical Information of China (English)

    王立峰; 范乐明; 陈丙莺; 刘宝瑞; 王若宁; 魏恩会


    Objective Lecithia: cholesterol acyltrmsfer ase (LCAT) is the major enzyme producing most plasma cholesterol esters( CE )and a key partiipant in the process of reverse cholesterol traansfer ( RCT). The aim of the study was to co-express LCAT and its nature activator apoA- I medi ated by recombinant adeno-associated virus vectors in the skeletal muscle cells, and open a new avenue of gene therapy touard the primary or secondary LCAT deficiency. Methods 293T cells were cotrans fected with pDG and rAAVAIL/rAAVL plasmid to produce infectious rAAV, and non-iouic iodixanol gradients centri f ngation followed by heparin affinity chromatography was per formed f or separation . pu rification and concentration of rAAV. The particle numbers of rAAV were assayed by dot-blot, then these vectors transduced C2C12 myoblasts. ELISA and Western Blot asasayed for human apoA- I and 3H-cholesterol labeled radiochemical methods for LCAT activity. Genomic DNA was extracted from transduced C2C12 and analyzed fo the presence of vector sequence by PCR amplifiations. Results The particle mumbers of rAAV were 7× 1014/L (rAAAIL) and 1 × 1014/L (rAAVL). The expres sion of human apoA- I cDNA and/or human LCAT cDNA in transduced C2C12 cells lasted for 3 0 d, even after myoblasts were differentiated into myotubes. PCR products for transgene indiated the long-term persistence of transduced vector sequences. Conclusion The result indicated that the meth ods used for production and purification of rAAV is an effiient and rAAV vector mediate the expres sion and secretion of LCAT and apoA- I gene in C2C12 myoblasts successfully. It suggested that the use of rAAV vectors mediating the high efficiency, long-term expression of human LCAT cDNA and/ or apoA- I cDNA in skeletal muscle in vivo might be a safe and fessible strategy to the gene therapy of LCAT deficiency.

  8. Epigenetic signature and enhancer activity of the human APOE gene (United States)

    Yu, Chang-En; Cudaback, Eiron; Foraker, Jessica; Thomson, Zachary; Leong, Lesley; Lutz, Franziska; Gill, James Anthony; Saxton, Aleen; Kraemer, Brian; Navas, Patrick; Keene, C. Dirk; Montine, Thomas; Bekris, Lynn M.


    The human apolipoprotein E (APOE) gene plays an important role in lipid metabolism. It has three common genetic variants, alleles ɛ2/ɛ3/ɛ4, which translate into three protein isoforms of apoE2, E3 and E4. These isoforms can differentially influence total serum cholesterol levels; therefore, APOE has been linked with cardiovascular disease. Additionally, its ɛ4 allele is strongly associated with the risk of Alzheimer's disease (AD), whereas the ɛ2 allele appears to have a modest protective effect for AD. Despite decades of research having illuminated multiple functional differences among the three apoE isoforms, the precise mechanisms through which different APOE alleles modify diseases risk remain incompletely understood. In this study, we examined the genomic structure of APOE in search for properties that may contribute novel biological consequences to the risk of disease. We identify one such element in the ɛ2/ɛ3/ɛ4 allele-carrying 3′-exon of APOE. We show that this exon is imbedded in a well-defined CpG island (CGI) that is highly methylated in the human postmortem brain. We demonstrate that this APOE CGI exhibits transcriptional enhancer/silencer activity. We provide evidence that this APOE CGI differentially modulates expression of genes at the APOE locus in a cell type-, DNA methylation- and ɛ2/ɛ3/ɛ4 allele-specific manner. These findings implicate a novel functional role for a 3′-exon CGI and support a modified mechanism of action for APOE in disease risk, involving not only the protein isoforms but also an epigenetically regulated transcriptional program at the APOE locus driven by the APOE CGI. PMID:23892237

  9. Role of urea on recombinant Apo A-I stability and its utilization in anion exchange chromatography. (United States)

    Angarita, Monica; Arosio, Paolo; Müller-Späth, Thomas; Baur, Daniel; Falkenstein, Roberto; Kuhne, Wolfgang; Morbidelli, Massimo


    Apolipoprotein A-I (Apo A-I) is an important lipid-binding protein involved in the transport and metabolism of cholesterol. High protein purity, in particular with respect to endotoxins is required for therapeutic applications. The use of urea during the purification process of recombinant Apo A-I produced in Escherichia coli has been suggested so as to provide high endotoxin clearance. In this work, we show that urea can be used as a sole modifier during the ion exchange chromatographic purification of Apo A-I and we investigate the molecular mechanism of elution by correlating the effect of urea on self-association, conformation and adsorption equilibrium properties of a modified model Apo A-I. In the absence of urea the protein was found to be present as a population of oligomers represented mainly by trimers, hexamers and nonamers. The addition of urea induced oligomer dissociation and protein structure unfolding. We correlated the changes in protein association and conformation with variations of the adsorption equilibrium of the protein on a strong anion exchanger. It was confirmed that the adsorption isotherms, described by a Langmuir model, were dependent on both protein and urea concentrations. Monomers, observed at low urea concentration (0.5M), were characterized by larger binding affinity and adsorption capacity compared to both protein oligomers (0M) and unfolded monomers (2-8M). The reduction of both the binding strength and maximum adsorption capacity at urea concentrations larger than 0.5M explains the ability of urea of inducing elution of the protein from the ion exchange resin. The dissociation of the protein complexes occurring during the elution could likely be the origin of the effective clearance of endotoxins originally trapped inside the oligomers.

  10. Comparison of Apolipoprotein (apoB/apoA-I) and Lipoprotein (Total Cholesterol/HDL) Ratio Determinants. Focus on Obesity, Diet and Alcohol Intake (United States)

    Tognon, Gianluca; Berg, Christina; Mehlig, Kirsten; Thelle, Dag; Strandhagen, Elisabeth; Gustavsson, Jaana; Rosengren, Annika; Lissner, Lauren


    The ratio between apolipoprotein B and apolipoprotein A-I (apoB/apoA-I) has been suggested to be a powerful and more accurate predictor of future cardiovascular disease risk than total cholesterol and HDL cholesterol. Since diet and lifestyle can directly influence dyslipidemia, it is of interest to identify modifiable factors that are associated with high levels of the apolipoprotein ratio and if they can have a different association with a more traditional indicator of cardiovascular risk such as total cholesterol/HDL. The relationship between obesity and dyslipidemia is established and it is of interest to determine which factors can modify this association. This study investigated the cross-sectional association of obesity, diet and lifestyle factors with apoB/apoA-I and total cholesterol/HDL respectively, in a Swedish population of 2,907 subjects (1,537 women) as part of the INTERGENE study. The apolipoprotein and lipoprotein ratios were highly correlated, particularly in women, and obesity was strongly associated with both. Additionally, age, cigarette smoking and alcohol intake were important determinants of these ratios. Alcohol was the only dietary factor that appreciably attenuated the association between obesity and each of the ratios, with a stronger attenuation in women. Other dietary intake and lifestyle-related factors such as smoking status and physical activity had a lower effect on this association. Because the apolipoprotein and lipoprotein ratios share similar diet and lifestyle determinants as well as being highly correlated, we conclude that either of these ratios may be a sufficient indicator of dyslipidemia. PMID:22848405

  11. Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice.

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    Pin Yue

    Full Text Available CD36 facilitates oxidized low density lipoprotein uptake and is implicated in development of atherosclerotic lesions. CD36 also binds unmodified high and very low density lipoproteins (HDL, VLDL but its role in the metabolism of these particles is unclear. Several polymorphisms in the CD36 gene were recently shown to associate with serum HDL cholesterol. To gain insight into potential mechanisms for these associations we examined HDL metabolism in CD36 null (CD36(-/- mice. Feeding CD36(-/- mice a high cholesterol diet significantly increased serum HDL, cholesterol and phospholipids, as compared to wild type mice. HDL apolipoproteins apoA-I and apoA-IV were increased and shifted to higher density HDL fractions suggesting altered particle maturation. Clearance of dual-labeled HDL was unchanged in CD36(-/- mice and cholesterol uptake from HDL or LDL by isolated CD36(-/- hepatocytes was unaltered. However, CD36(-/- hepatocytes had higher cholesterol and phospholipid efflux rates. In addition, expression and secretion of apoA-I and apoA-IV were increased reflecting enhanced PXR. Similar to hepatocytes, cholesterol and phospholipid efflux were enhanced in CD36(-/- macrophages without changes in protein levels of ABCA1, ABCG1 or SR-B1. However, biotinylation assays showed increased surface ABCA1 localization in CD36(-/- cells. In conclusion, CD36 influences reverse cholesterol transport and hepatic ApoA-I production. Both pathways are enhanced in CD36 deficiency, increasing HDL concentrations, which suggests the potential benefit of CD36 inhibition.

  12. Ecto-F_1-ATPase: A moonlighting protein complex and an unexpected apoA-I receptor

    Institute of Scientific and Technical Information of China (English)

    Pierre; Vantourout; Claudia; Radojkovic; Laeticia; Lichtenstein; Véronique; Pons; Eric; Champagne; Laurent; O; Martinez


    Mitochondrial ATP synthase has been recently detected at the surface of different cell types, where it is a high affinity receptor for apoA-I, the major protein component in high density lipoproteins (HDL). Cell surface ATP synthase (namely ecto-F1-ATPase) expression is related to different biological effects, such as regulation of HDL uptake by hepatocytes, endothelial cell proliferation or antitumor activity of Vγ9/Vδ2 T lymphocytes. This paper reviews the recently discovered functions and regulations of ...

  13. ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation. (United States)

    Lindahl, Maria; Petrlova, Jitka; Dalla-Riva, Jonathan; Wasserstrom, Sebastian; Rippe, Catarina; Domingo-Espin, Joan; Kotowska, Dorota; Krupinska, Ewa; Berggreen, Christine; Jones, Helena A; Swärd, Karl; Lagerstedt, Jens O; Göransson, Olga; Stenkula, Karin G


    ApoA-I, the main protein component of HDL, is suggested to be involved in metabolic homeostasis. We examined the effects of Milano, a naturally occurring ApoA-I variant, about which little mechanistic information is available. Remarkably, high-fat-fed mice treated with Milano displayed a rapid weight loss greater than ApoA-I WT treated mice, and a significantly reduced adipose tissue mass, without an inflammatory response. Further, lipolysis in adipose cells isolated from mice treated with either WT or Milano was increased. In primary rat adipose cells, Milano stimulated cholesterol efflux and increased glycerol release, independently of β-adrenergic stimulation and phosphorylation of hormone sensitive lipase (Ser563) and perilipin (Ser522). Stimulation with Milano had a significantly greater effect on glycerol release compared with WT but similar effect on cholesterol efflux. Pharmacological inhibition or siRNA silencing of ABCA1 did not diminish Milano-stimulated lipolysis, although binding to the cell surface was decreased, as analyzed by fluorescence microscopy. Interestingly, methyl-β-cyclodextrin, a well-described cholesterol acceptor, dose-dependently stimulated lipolysis. Together, these results suggest that decreased fat mass and increased lipolysis following Milano treatment in vivo is partly explained by a novel mechanism at the adipose cell level comprising stimulation of lipolysis independently of the canonical cAMP/protein kinase A signaling pathway. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  14. Amyloidogenic propensity of a natural variant of human apolipoprotein A-I: stability and interaction with ligands.

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    Silvana A Rosú

    Full Text Available A number of naturally occurring mutations of human apolipoprotein A-I (apoA-I have been associated with hereditary amyloidoses. The molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here we examined the effects of the Arg173Pro point mutation in apoA-I on the structure, stability, and aggregation propensity, as well as on the ability to bind to putative ligands. Our results indicate that the mutation induces a drastic loss of stability, and a lower efficiency to bind to phospholipid vesicles at physiological pH, which could determine the observed higher tendency to aggregate as pro-amyloidogenic complexes. Incubation under acidic conditions does not seem to induce significant desestabilization or aggregation tendency, neither does it contribute to the binding of the mutant to sodium dodecyl sulfate. While the binding to this detergent is higher for the mutant as compared to wt apoA-I, the interaction of the Arg173Pro variant with heparin depends on pH, being lower at pH 5.0 and higher than wt under physiological pH conditions. We suggest that binding to ligands as heparin or other glycosaminoglycans could be key events tuning the fine details of the interaction of apoA-I variants with the micro-environment, and probably eliciting the toxicity of these variants in hereditary amyloidoses.

  15. Disruption of human plasma high-density lipoproteins by streptococcal serum opacity factor requires labile apolipoprotein A-I. (United States)

    Han, Mikyung; Gillard, Baiba K; Courtney, Harry S; Ward, Kathryn; Rosales, Corina; Khant, Htet; Ludtke, Steven J; Pownall, Henry J


    Human plasma high-density lipoproteins (HDL), the primary vehicle for reverse cholesterol transport, are the target of serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes that turns serum opaque. HDL comprise a core of neutral lipidscholesteryl esters and some triglyceridesurrounded by a surface monolayer of cholesterol, phospholipids, and specialized proteins [apolipoproteins (apos) A-I and A-II]. A HDL is an unstable particle residing in a kinetic trap from which it can escape via chaotropic, detergent, or thermal perturbation. Recombinant (r) SOF catalyzes the transfer of nearly all neutral lipids of approximately 100,000 HDL particles (D approximately 8.5 nm) into a single, large cholesteryl ester-rich microemulsion (CERM; D > 100 nm), leaving a new HDL-like particle [neo HDL (D approximately 5.8 nm)] while releasing lipid-free (LF) apo A-I. CERM formation and apo A-I release have similar kinetics, suggesting parallel or rapid consecutive steps. By using complementary physicochemical methods, we have refined the mechanistic model for HDL opacification. According to size exclusion chromatography, a HDL containing nonlabile apo A-I resists rSOF-mediated opacification. On the basis of kinetic cryo-electron microscopy, rSOF (10 nM) catalyzes the conversion of HDL (4 microM) to neo HDL via a stepwise mechanism in which intermediate-sized particles are seen. Kinetic turbidimetry revealed opacification as a rising exponential reaction with a rate constant k of (4.400 +/- 0.004) x 10(-2) min(-1). Analysis of the kinetic data using transition state theory gave an enthalpy (DeltaH()), entropy (DeltaS(++)), and free energy (DeltaG()) of activation of 73.9 kJ/mol, -66.87 J/K, and 94.6 kJ/mol, respectively. The free energy of activation for opacification is nearly identical to that for the displacement of apo A-I from HDL by guanidine hydrochloride. We conclude that apo A-I lability is required for HDL opacification, LF apo A-I desorption is the

  16. Síntesis y caracterización de la variante de la Apolipoproteína A-I (APO A-I Zaragoza) y análisis de posibilidades de uso farmacológico


    Fiddyment Puertas, Sarah; García Otín, Angel Luis; Pocovi Mieras, Miguel


    La apolipoproteína A-I Zaragoza (apo A-I Z, mutación L144R) es una variante de la apolipoproteína A-I cuyos portadores tienen muy baja concentración de colesterol-HDL (c-HDL) pero, aunque presenten factores de riesgo aterogénicos adicionales, paradójicamente no muestran signos de aterosclerosis a nivel subclínico. Estudios metabólicos in vivo realizados previamente en portadores heterocigotos de esta variante de apo A-I revelaron que tiene una tasa de catabolismo que duplica la de la proteína...

  17. Human apolipoprotein A-I is associated with dengue virus and enhances virus infection through SR-BI.

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    Yujia Li

    Full Text Available Diseases caused by dengue virus (DV infection vary in severity, with symptoms ranging from mild fever to life threatening dengue hemorrhage fever (DHF and dengue shock syndrome (DSS. Clinical studies have shown that significant decrease in the level of lipoproteins is correlated with severe illness in DHF/DSS patients. Available evidence also indicates that lipoproteins including high-density lipoprotein (HDL and low-density lipoprotein (LDL are able to facilitate cell entry of HCV or other flaviviruses via corresponding lipoprotein receptors. In this study, we found that pre-incubation of DV with human serum leads to an enhanced DV infectivity in various types of cells. Such enhancement could be due to interactions between serum components and DV particles. Through co-immunoprecipitation we revealed that apolipoprotein A-I (ApoA-I, the major protein component in HDL, is associated with DV particles and is able to promote DV infection. Based on that observation, we further found that siRNA knockdown of the scavenger receptor class B type I (SR-BI, the cell receptor of ApoA-I, abolished the activity of ApoA-I in enhancement of DV infection. This suggests that ApoA-I bridges DV particles and cell receptor SR-BI and facilitates entry of DV into cells. FACS analysis of cell surface dengue antigen after virus absorption further confirmed that ApoA-I enhances DV infection via promoting initial attachment of the virus to cells. These findings illustrate a novel entry route of DV into cells, which may provide insights into the functional importance of lipoproteins in dengue pathogenesis.

  18. Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2. (United States)

    Vandal, Milène; Alata, Wael; Tremblay, Cyntia; Rioux-Perreault, Christine; Salem, Norman; Calon, Frédéric; Plourde, Mélanie


    Benefits on cognition from docosahexaenoic acid (DHA, 22 : 6 n-3) intake are absent in humans carrying apolipoprotein E ε4 allele (APOE4), the most important genetic risk factor for Alzheimer's disease (AD). To test the hypothesis that carrying APOE4 impairs DHA distribution, we evaluated plasma and brain fatty acid profiles and uptake of [(14) C]-DHA using in situ cerebral perfusion through the blood-brain barrier in 4- and 13-month-old male and female APOE-targeted replacement mice (APOE2, APOE3, and APOE4), fed with a DHA-depleted diet. Cortical and plasma DHA were 9% lower and 34% higher in APOE4 compared to APOE2 mice, respectively. Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. A significant relationship was established between DHA and apoE concentrations in the cortex of mice (r(2) = 0.21) and AD patients (r(2) = 0.32). Altogether, our results suggest that lower brain uptake of DHA in APOE4 than in APOE2 mice may limit the accumulation of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of AD. Using human APOE2, 3, and 4 isoform-specific transgenic mice, we found a lower brain uptake of docosahexaenoic acid (DHA) in APOE4 than in APOE2 mice that may limit the biodistribution of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of Alzheimer's disease (AD).

  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

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    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. ApoA-I enhances generation of HDL-like lipoproteins through interaction between ABCA1 and phospholipase Cγ in rat astrocytes. (United States)

    Ito, Jin-ichi; Nagayasu, Yuko; Kheirollah, Alireza; Abe-Dohmae, Sumiko; Yokoyama, Shinji


    In the previous paper, we reported that apolipoprotein (apo) A-I enhances generation of HDL-like lipoproteins in rat astrocytes to be accompanied with both increase in tyrosine phosphorylation of phospholipase Cγ (PL-Cγ) and PL-Cγ translocation to cytosolic lipid-protein particles (CLPP) fraction. In this paper, we studied the interaction between apoA-I and ATP-binding cassette transporter A1 (ABCA1) to relate with PL-Cγ function for generation of HDL-like lipoproteins in the apoA-I-stimulated astrocytes. ABCA1 co-migrated with exogenous apoA-I with apparent molecular weight over 260kDa on SDS-PAGE when rat astrocytes were treated with apoA-I and then with a cross-linker, BS3. The solubilized ABCA1 of rat astrocytes was associated with the apoA-I-immobilized Affi-Gel 15. An LXR agonist, To901317, increased the cellular level of ABCA1, association of apoA-I with ABCA1 and apoA-I-mediated lipid release in rat astrocytoma GA-1/Mock cells where ABCA1 expression at baseline is very low. PL-Cγ was co-isolated by apoA-I-immobilized Affi-Gel 15 and co-immunoprecipitated by anti-ABCA1 antibody along with ABCA1 from the solubilized membrane fraction of rat astrocytes. The SiRNA of ABCA1 suppressed not only the PL-Cγ binding to ABCA1 but also the tyrosine phosphorylation of PL-Cγ. A PL-C inhibitor, U73122, prevented generation of apoA-I-mediated HDL-like lipoproteins in rat astrocytes. To901317 increased the association of PL-Cγ with ABCA1 in GA-1/Mock cells dependently on the increase of cellular level of ABCA1 without changing that of PL-Cγ. These findings suggest that the exogenous apoA-I augments the interaction between PL-Cγ and ABCA1 to stimulate tyrosine phosphorylation and activation of PL-Cγ for generation of HDL-like lipoproteins in astrocytes.

  1. Serum opacity factor unmasks human plasma high-density lipoprotein instability via selective delipidation and apolipoprotein A-I desorption. (United States)

    Gillard, Baiba K; Courtney, Harry S; Massey, John B; Pownall, Henry J


    Human plasma high-density lipoproteins (HDL) are important vehicles in reverse cholesterol transport, the cardioprotective mechanism by which peripheral tissue-cholesterol is transported to the liver for disposal. HDL is the target of serum opacity factor (SOF), a substance produced by Streptococcus pyogenes that turns mammalian serum cloudy. Using a recombinant (r) SOF, we studied opacification and its mechanism. rSOF catalyzes the partial disproportionation of HDL into a cholesteryl ester-rich microemulsion (CERM) and a new HDL-like particle, neo HDL, with the concomitant release of lipid-free (LF)-apo A-I. Opacification is unique; rSOF transfers apo E and nearly all neutral lipids of approximately 100,000 HDL particles into a single large CERM whose size increases with HDL-CE content (r approximately 100-250 nm) leaving a neo HDL that is enriched in PL (41%) and protein (48%), especially apo A-II. rSOF is potent; within 30 min at 37 degrees C, 10 nM rSOF opacifies 4 microM HDL. At respective low and high physiological HDL concentrations, LF-apo A-I is monomeric and tetrameric. CERM formation and apo A-I release have similar kinetics suggesting parallel or rapid sequential steps. According to the reaction products and kinetics, rSOF is a heterodivalent fusogenic protein that uses a docking site to displace apo A-I and bind to exposed CE surfaces on HDL; the resulting rSOF-HDL complex recruits additional HDL with its binding-delipidation site and through multiple fusion steps forms a CERM. rSOF may be a clinically useful and novel modality for improving reverse cholesterol transport. With apo E and a high CE content, CERM could transfer large amounts of cholesterol to the liver for disposal via the LDL receptor; neo HDL is likely a better acceptor of cellular cholesterol than HDL; LF-apo A-I could enhance efflux via the ATP-binding casette transporter ABCA1.

  2. Secondary structure changes in ApoA-I Milano (R173C are not accompanied by a decrease in protein stability or solubility.

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    Jitka Petrlova

    Full Text Available Apolipoprotein A-I (apoA-I is the main protein of high-density lipoprotein (HDL and a principal mediator of the reverse cholesterol transfer pathway. Variants of apoA-I have been shown to be associated with hereditary amyloidosis. We previously characterized the G26R and L178H variants that both possess decreased stability and increased fibril formation propensity. Here we investigate the Milano variant of apoAI (R173C; apoAI-M, which despite association with low plasma levels of HDL leads to low prevalence of cardiovascular disease in carriers of this mutation. The R173C substitution is located to a region (residues 170 to 178 that contains several fibrillogenic apoA-I variants, including the L178H variant, and therefore we investigated a potential fibrillogenic property of the apoAI-M protein. Despite the fact that apoAI-M shared several features with the L178H variant regarding increased helical content and low degree of ThT binding during prolonged incubation in physiological buffer, our electron microscopy analysis revealed no formation of fibrils. These results suggest that mutations inducing secondary structural changes may be beneficial in cases where fibril formation does not occur.

  3. Persistent organochlorine pollutants and risk for skeletal fractures and impaired bone mineral density in humans. Results from the ''COMPARE'' project

    Energy Technology Data Exchange (ETDEWEB)

    Hagmar, L.; Wallin, E.; Joensson, B.A. [Department of Occupational and Environmental Medicine, Lund (Sweden)


    Persistent organochlorine pollutants (POP) have, in animal studies, impaired normal bone metabolism and resulted in increased bone fragility. Especially considering the dramatical increase in osteoporotic fractures in western societies during the last decades, it is a pertinent question whether a high dietary intake of POP might pose a risk for deteriorated bone quality in humans. This problem has been assessed as a part of the collaborative project ''COMPARE'', funded by European Commission RD Life Science Program. As a study base we have used cohorts of Swedish fishermen's families. We have earlier shown that fishermen living at the east coast of Sweden, have a high consumption of contaminated fatty fish from the Baltic Sea and consequently relatively high exposure levels for various POPs, also compared with fishermen from the Swedish west coast. Such a discrepancy was also found for fishermen's wives. The aim of the project was to assess in epidemiological studies whether a high dietary intake of POP through fatty fish from the Baltic may result in an increased incidence of osteoporotic fractures or decreased bone mineral density (BMD). We give here an overview of the results.

  4. Effects of Iron Supplementation With and Without Docosahexaenoic Acid on the Cardiovascular Disease Risk Based on Paraoxonase-1, hs-CRP, and ApoB/ApoA-I Ratio in Women with Iron Deficiency Anemia. (United States)

    Shidfar, Farzad; Amani, Samira; Vafa, Mohammadreza; Shekarriz, Ramin; Hosseini, Sharieh; Shidfar, Shahrzad; Eshraghian, Mohammadreza; Mousavi, Seyedeh Neda


    Numerous studies have demonstrated that tissue deposition of iron following prolonged high dose of oral supplementation for treatment of iron deficiency anemia (IDA) leads to body iron overload and oxidative stress, which starts the process of atherosclerosis. This study aimed to determine the effect of iron supplementation in combination with docosahexaenoic acid (DHA) on the cardiovascular disease risk based on paraoxonase-1 (PON-1), high-sensitivity C-reactive protein (hs-CRP), and ApoB/ApoA-I ratio in women with IDA. In this randomized controlled trial, 76 women with IDA, aged 15-45 years, were included. The patients were randomly assigned to receive 500 mg of DHA supplement or placebo with an iron tablet, once daily for 12 weeks. The participants were assessed by measurement of the serum iron, ferritin, PON-1, hs-CRP levels, and the ApoB/ApoA-I ratio at the beginning and end of study. Serum hs-CRP decreased in the DHA-supplemented group (p = 0.036), and ApoA-I decreased in the placebo group (p = 0.013). No significant difference was detected for the serum PON-1 concentration and the ApoB/ApoA-I ratio in two groups. Iron supplementation combined with DHA may have favorable effects on serum hs-CRP in women with IDA.

  5. Effects of blackberry (Morus nigra L.) consumption on serum concentration of lipoproteins, apo A-I, apo B, and high-sensitivity-C-reactive protein and blood pressure in dyslipidemic patients. (United States)

    Aghababaee, Sahar Keshtkar; Vafa, Mohammadreza; Shidfar, Farzad; Tahavorgar, Atefeh; Gohari, Mahmoodreza; Katebi, Davod; Mohammadi, Vida


    This study investigated blackberry (Persian mulberry) effects on apo A-I, apo B, high-sensitivity-C-reactive protein (hs-CRP), and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in dyslipidemic patients. In this 8-week randomized clinical trial, 72 dyslipidemic patients were randomly divided into two groups: Intervention (300 mL/day blackberry juice with pulp) and control group (usual diets). Before and after the intervention, fasting blood samples were taken from both groups and serum concentration of lipoprotein, apo A-I and apo B, serum lipids (total cholesterol, low-density lipoprotein, high-density lipoprotein [HDL], and triglyceride), hs-CRP were measured. Blood pressure before and after the study was measured with a mercury manometer. At week 8 in the intervention group, apo A-I and HDL increased significantly (P = 0.015, P = 0.001, respectively), apo B and hs-CRP decreased significantly (P = 0.044, P = 0.04, respectively). Mean changes in apo A-I and HDL and apo B/apo A-I ratio were significant between the groups (P = 0.005, P = 0.014, and P = 0.009, respectively). After 8 weeks, there was a significant difference between hs-CRP mean values (P = 0.01) of the groups. At week 8, SBP decreased significantly (P = 0.005) in the intervention group with no significant differences for SBP mean values between the groups. No significant changes were observed in other lipid parameters and DBP in the intervention group and between the groups. Blackberry consumption may exert beneficial effects on apolipoproteins, blood pressure, and inflammatory markers in individuals with lipid disorders.

  6. Effects of blackberry (Morus nigra L. consumption on serum concentration of lipoproteins, apo A-I, apo B, and high-sensitivity-C-reactive protein and blood pressure in dyslipidemic patients

    Directory of Open Access Journals (Sweden)

    Sahar Keshtkar Aghababaee


    Full Text Available Background: This study investigated blackberry (Persian mulberry effects on apo A-I, apo B, high-sensitivity-C-reactive protein (hs-CRP, and systolic blood pressure (SBP and diastolic blood pressure (DBP in dyslipidemic patients. Materials and Methods: In this 8-week randomized clinical trial, 72 dyslipidemic patients were randomly divided into two groups: Intervention (300 mL/day blackberry juice with pulp and control group (usual diets. Before and after the intervention, fasting blood samples were taken from both groups and serum concentration of lipoprotein, apo A-I and apo B, serum lipids (total cholesterol, low-density lipoprotein, high-density lipoprotein [HDL], and triglyceride, hs-CRP were measured. Blood pressure before and after the study was measured with a mercury manometer. Results: At week 8 in the intervention group, apo A-I and HDL increased significantly (P = 0.015, P = 0.001, respectively, apo B and hs-CRP decreased significantly (P = 0.044, P = 0.04, respectively. Mean changes in apo A-I and HDL and apo B/apo A-I ratio were significant between the groups (P = 0.005, P = 0.014, and P = 0.009, respectively. After 8 weeks, there was a significant difference between hs-CRP mean values (P = 0.01 of the groups. At week 8, SBP decreased significantly (P = 0.005 in the intervention group with no significant differences for SBP mean values between the groups. No significant changes were observed in other lipid parameters and DBP in the intervention group and between the groups. Conclusion: Blackberry consumption may exert beneficial effects on apolipoproteins, blood pressure, and inflammatory markers in individuals with lipid disorders.

  7. Effects of blackberry (Morus nigra L.) consumption on serum concentration of lipoproteins, apo A-I, apo B, and high-sensitivity-C-reactive protein and blood pressure in dyslipidemic patients (United States)

    Aghababaee, Sahar Keshtkar; Vafa, Mohammadreza; Shidfar, Farzad; Tahavorgar, Atefeh; Gohari, Mahmoodreza; Katebi, Davod; Mohammadi, Vida


    Background: This study investigated blackberry (Persian mulberry) effects on apo A-I, apo B, high-sensitivity-C-reactive protein (hs-CRP), and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in dyslipidemic patients. Materials and Methods: In this 8-week randomized clinical trial, 72 dyslipidemic patients were randomly divided into two groups: Intervention (300 mL/day blackberry juice with pulp) and control group (usual diets). Before and after the intervention, fasting blood samples were taken from both groups and serum concentration of lipoprotein, apo A-I and apo B, serum lipids (total cholesterol, low-density lipoprotein, high-density lipoprotein [HDL], and triglyceride), hs-CRP were measured. Blood pressure before and after the study was measured with a mercury manometer. Results: At week 8 in the intervention group, apo A-I and HDL increased significantly (P = 0.015, P = 0.001, respectively), apo B and hs-CRP decreased significantly (P = 0.044, P = 0.04, respectively). Mean changes in apo A-I and HDL and apo B/apo A-I ratio were significant between the groups (P = 0.005, P = 0.014, and P = 0.009, respectively). After 8 weeks, there was a significant difference between hs-CRP mean values (P = 0.01) of the groups. At week 8, SBP decreased significantly (P = 0.005) in the intervention group with no significant differences for SBP mean values between the groups. No significant changes were observed in other lipid parameters and DBP in the intervention group and between the groups. Conclusion: Blackberry consumption may exert beneficial effects on apolipoproteins, blood pressure, and inflammatory markers in individuals with lipid disorders. PMID:26622259

  8. Apo A-I promoter polymorphism influences basal HDL-cholesterol and its response to pravastatin therapy. (United States)

    Lahoz, Carlos; Peña, Rocío; Mostaza, Jose M; Jiménez, Javier; Subirats, Enric; Pintó, Xavier; Taboada, Manuel; López-Pastor, Angela


    Statins decrease cardiovascular morbidity and mortality, essentially, by reducing LDL-cholesterol levels and, additionally, by increasing HDL-cholesterol concentrations. Environmental and genetic factors are known to affect LDL-C response to statins but less is known regarding HDL-C. We have evaluated the lipid and lipoprotein response to 20 mg/day of pravastatin for 16 weeks in relation to the G/A polymorphism in the promoter region of the apo A-I gene in 397 hypercholesterolaemic subjects followed-up on an out-patient basis. In the study population, 61.7% were homozygous for the G allele and 36% were heterozygous. The A allele carriers had an HDL-C 6.5% higher than the G allele homozygotes (P=0.021 in univariate analysis; P=0.009 in multivariate analysis). However, on segregation by gender and smoking status the effect was significant only in non-smoking males. The A allele carriers did not increase their HDL-C concentrations after treatment (-0.3, 95%CI -3.3 to 2.7%) while G allele homozygotes had a 4.9% increase (95%CI 2.5-7.3%). Differences in the response between both groups were significant before (P=0.008) and after adjustment for confounding variables such as age and baseline HDL-C concentration (P=0.046). We conclude that the G/A polymorphism of the apo A-I promoter region affects not only baseline HDL-C concentrations but also its response to pravastatin treatment.

  9. Exercise, APOE genotype, and the evolution of the human lifespan (United States)

    Raichlen, David A.; Alexander, Gene E.


    Humans have exceptionally long lifespans compared with other mammals. However, our longevity evolved when our ancestors had two copies of the apolipoprotein E (APOE) ε4 allele, a genotype that leads to a high risk of Alzheimer’s disease (AD), cardiovascular disease, and increased mortality. How did human aging evolve within this genetic constraint? Drawing from neuroscience, anthropology, and brain-imaging research, we propose the hypothesis that the evolution of increased physical activity approximately 2 million years ago served to reduce the amyloid plaque and vascular burden of APOE ε4, relaxing genetic constraints on aging. This multidisciplinary approach links human evolution with health and provides a complementary perspective on aging and neurodegenerative disease that may help identify key mechanisms and targets for intervention. PMID:24690272

  10. APOA1-75 G to A Substitution Associated with Severe Forms of CAD, Lower Levels of HDL and apoA-I among Northern Indians

    Directory of Open Access Journals (Sweden)

    S. Chhabra


    DVD, TVD was 1.3, 2.8 and 4.2 respectively (ptrend = 0.007. Analysis of intergenotypic variations in the lipid profile revealed significantly lower levels of HDL and apoA-I among ‘A’ allele carriers as compared to GG (patients. Our study, first of its kind from India, suggests that ‘A’ allele may contribute to severity of CAD and low levels of HDL & apoA-I. However, an in depth study with a larger set of sample is necessary.

  11. "Human Nature": Chemical Engineering Students' Ideas about Human Relationships with the Natural World (United States)

    Goldman, Daphne; Assaraf, Orit Ben-Zvi; Shemesh, Julia


    While importance of environmental ethics, as a component of sustainable development, in preparing engineers is widely acknowledged, little research has addressed chemical engineers' environmental concerns. This study aimed to address this void by exploring chemical engineering students' values regarding human-nature relationships. The…

  12. Novel pathways of apolipoprotein A-I metabolism in HDL of different sizes in humans (United States)

    Mendivil, Carlos O.; Furtado, Jeremy; Morton, Allyson M.; Wang, Liyun; Sacks, Frank M.


    Objective A prevailing concept is that HDL is secreted into the systemic circulation as a small mainly discoidal particle; which expands progressively and becomes spherical by uptake and esterification of cellular cholesterol; and then contracts by cholesterol ester delivery to the liver, a process known as reverse cholesterol transport, thought to be impaired in people with low HDL cholesterol (HDLc). This metabolic framework has not been established in humans. Approach and results We studied the metabolism of apolipoproteinA-I in four standard HDL sizes by endogenous isotopic labeling in six overweight adults with low HDLc and in six adults with normal body weight with high plasma HDLc. Contrary to expectation, HDL was secreted into the circulation in its entire size distribution from very small to very large, similarly in both groups. Very small (prebeta) HDL comprised only 8% of total apoA-I secretion. Each HDL subfraction circulated mostly within its secreted size range for 1–4 days, and then was cleared. Enlargement of very small and medium to large and very large HDL, and generation of very small from medium HDL were minor metabolic pathways. Prebeta HDL was cleared slower whereas medium, large and very large HDL were cleared faster in the low HDLc group. Conclusions A new model is proposed from these results in which HDL is metabolized in plasma mainly within several discrete, stable sizes, across the common range of HDLc concentrations. PMID:26543096

  13. Chronic exposure to chlorpyrifos triggered body weight increase and memory impairment depending on human apoE polymorphisms in a targeted replacement mouse model. (United States)

    Peris-Sampedro, Fiona; Basaure, Pia; Reverte, Ingrid; Cabré, Maria; Domingo, José L; Colomina, Maria Teresa


    Despite restrictions on their use, humans are still constantly exposed to organophosphates (OPs). A huge number of studies have ratified the neurotoxic effects of chlorpyrifos (CPF) and suggested its association with neurodegenerative diseases, but data are still scarce. Human apolipoprotein E (apoE) plays an important role in lipid transport and distribution. In humans, the apoE4 isoform has been linked to an increased risk of Alzheimer's disease (AD). ApoE3 is the most prevalent isoform worldwide, and has been often established as the healthful one. The current study, performed in targeted replacement (TR) adult male mice, aimed to inquire whether genetic variations of the human apoE respond differently to a chronic dietary challenge with CPF. At four/five months of age, mice carrying apoE2, apoE3 or apoE4 were pair-fed a diet supplemented with CPF at 0 or 2mg/kg body weight/day for 13weeks. Cholinergic signs were monitored daily and body weight changes weekly. In the last week of treatment, learning and memory were assessed in a Barnes maze task. Dietary CPF challenge increased body weight only in apoE3 mice. Differences in the acquisition and retention of the Barnes maze were attributed to apoE genetic differences. Our results showed that apoE4 mice performed worse than apoE2 and apoE3 carriers in the acquisition period of the spatial task, and that apoE2 mice had poorer retention than the other two genotypes. On the other hand, CPF increased the search velocity of apoE2 subjects during the acquisition period. Retention was impaired only in CPF-exposed apoE3 mice. These results underline that gene×environment interactions need to be taken into account in epidemiological studies. Given that apoE3, the most common polymorphism in humans, has proved to be the most sensitive to CPF, the potential implications for human health merit serious thought.

  14. Human apoB contributes to increased serum total apo(a level in LPA transgenic mice

    Directory of Open Access Journals (Sweden)

    Teivainen Päivi A


    Full Text Available Abstract Background The Lp(a lipoprotein (Lp(a consists of the polymorphic glycoprotein apolipoprotein(a (apo(a, which is attached by a disulfide bond to apolipoprotein B (apoB. Apo(a, which has high homology with plasminogen, is present only in primates and hedgehogs. However, transgenic mice and rabbits with high serum apo(a levels exist. Liver is the main site for apo(a synthesis, but the site of removal is uncertain. To examine differences between transgenic mice expressing the LPA gene and mice capable of forming Lp(a particles, LPA-YAC transgenic mice and hAPOB transgenic mice were crossed and their offspring examined. Results Comparison of LPA-YAC with LPA-YAC/hAPOB transgenic mice showed that LPA-YAC/hAPOB transgenic mice have higher serum total apo(a and total cholesterol level than mice lacking the hAPOB gene. However, hepatic apo(a mRNA level was higher in LPA-YAC transgenic mice than in LPA-YAC/hAPOB transgenic mice. Feeding of a high-cholesterol/high-fat diet to male LPA-YAC transgenic mice with or without the hAPOB gene resulted in reduced serum total apo(a and hepatic apo(a mRNA level. Conclusion In conclusion, the higher serum total apo(a level in LPA-YAC/hAPOB transgenic mice than in LPA-YAC transgenic mice is not caused by increased apo(a synthesis. Lower hepatic apo(a mRNA level in LPA-YAC/hAPOB than in LPA-YAC transgenic mice may suggest that the increase in total apo(a level is a result of apo(a accumulation in serum. Furthermore, observed higher serum total cholesterol level in LPA-YAC/hAPOB transgenic mice than either in wild type or LPA-YAC transgenic mice may further suggest that human APOB transgenicity is a factor that contributes to increased serum total apo(a and cholesterol levels. Our results on reduced serum total apo(a and hepatic apo(a mRNA levels in HCHF fed male LPA-YAC transgenic mice confirm earlier findings in females, and show that there are no sex difference in mechanisms for lowering apo(a level in

  15. High-density lipoprotein associated factors apoA-I and serum amyloid A in Chinese non-diabetic patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    CHEN Guo-liang; LIU Li-wei; XIE Shuang; LIU Hong; LIU Yu-qing; LI Yi-shi


    Background High-density lipoprotein cholesterol(HDL-C)levels are a strong,independent inverse predictor of coronary heart disease (CHD).In this cross-sectional study we investigated the interrelationships between HDL-C and HDL relaled factors apolipoprotein A-I(apoA-I)and serum amyloid A(SAA)and the presence and extent of CHD in a population of Chinese patients with CHD. Methods Two hundred and twenty-four consecutive patients took part in this study.Demographic data were obtained from hospital records.Serum chemical concentrations were measured by standard laboratory methods.Reaults The concentrations of high-sensitive C-reactive protein(hsCRP)(median:1.85 mg/L)and SAP,(median:9.40 mg/L)were significantly higher in the CHD group(P<0.05),while concentrations of HDL-C(0.03±0.25)mmol/L)and apoA-I((604.59±1 05.79)mmol/L)were significantly lower than those in the non-CHD group(P<0.05).The concentrations of apoA-l decreased with the increase in vascular damage.but the difference did not reach statistical significance.However, the concentrations of hsCRP and SAA increased with the increase in vascular damage.The unadjusted odd ratios(ORs)(CI) for apoA-I and SAA of the presence of CHD were 0.093(0.990-0.997)(P=0.00)and 2.571(1.029-6.424)(P<0.05),respectively.The association between elevated SAA and the presence of CHD was lost after adjusting for lipid status parameter concentrations.The associations between apoA-I.SAA and the extent of CHD remained strong,regardless of confounding variables.Conclusions Increased concentrations of SAA represent the inflammatory marker of the extent of coronary stenosis in patients with CHD.In contrast to SAA, the level of apoA-I was also associated with the presence of CHD, indicating that apoA-I was not only a marker of CHD presence but also a quantitative indicator of CHD extent.In short.determining the change apolipoprotein content within HDL particle is a more accurate and effective method to evaluate the impact of HDL on CHD.

  16. Photoluminescence of acupoint &apos;Waiqiu&apos; in human superficial fascia

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Yuan [Synchrotron Radiation Research Center, Department of Physics, Surface Physics Laboratory (State Key Laboratory) of Fudan University, Shanghai 200433 (China); Yan Xiaohui [Synchrotron Radiation Research Center, Department of Physics, Surface Physics Laboratory (State Key Laboratory) of Fudan University, Shanghai 200433 (China); Liu Chenglin [Synchrotron Radiation Research Center, Department of Physics, Surface Physics Laboratory (State Key Laboratory) of Fudan University, Shanghai 200433 (China); Dang Ruishan [Second Military Medical University, Shanghai 200433 (China); Zhang Xinyi [Synchrotron Radiation Research Center, Department of Physics, Surface Physics Laboratory (State Key Laboratory) of Fudan University, Shanghai 200433 (China) and Shanghai Research Center of Acupuncture and Meridian, Pudong, Shanghai 201203 (China)]. E-mail:


    The spectral characters of an acupuncture point named &apos;Waiqiu&apos; in superficial fascia tissue have been studied by photoluminescence (PL) spectroscopy under the excitation of 457.9 nm. The PL around &apos;Waiqiu&apos; acupuncture point consists of two sub-bands resulting from the flavin adenine dinucleotide (FAD) and phospholipids, and the porphyrins (including purine, isoxanthopterin and tryptophan), respectively. More emission due to FAD and phospholipids is found inside the acupuncture effect area of &apos;Waiqiu&apos; than its marginal or outside acupuncture regions. The ratio of emission intensity of FAD and phospholipids to one of porphyrins gradually decreases along the direction away from the center of the acupuncture point. It implies that the component proportion changes between FAD, phospholipids and porphyrins around the &apos;Waiqiu&apos; acupuncture point. We suggest that there might be a certain relationship between redox function of FAD and &apos;Waiqiu&apos; acupuncture effect.

  17. Impacts of office design characteristics on human energy expenditure: developing a &apos;'KINESIS'&apos; model

    Energy Technology Data Exchange (ETDEWEB)

    Rassia, Stamatina T.; Baker, Nick V. [University of Cambridge, Martin Centre for Architectural and Urban Studies, Department of Architecture, Cambridge (United Kingdom); Alexiou, Alexandros [University of Cambridge, Department of Land Economy, Cambridge (United Kingdom)


    Over the last few decades, research in public health has associated inactivity with a number of ailments and chronic diseases, such as colon cancer, type II diabetes, osteoporosis and coronary heart disease. In the belief that the office building substantially shapes occupant daily activity, this work draws upon qualitative and quantitative monitoring of human activity within office buildings during typical working weeks. This research is based on data collection results regarding the design of space in relation to energy expenditure and it presents a quantitative model (named KINESIS after the Greek word for activity) that, in the form of a set equation, can simulate and estimate the total energy expenditure per person per day in a given office layout. (orig.)

  18. Mitochondrial function is involved in regulation of cholesterol efflux to apolipoprotein (apoA-I from murine RAW 264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Allen Anne Marie


    Full Text Available Abstract Background Mitochondrial DNA damage, increased production of reactive oxygen species and progressive respiratory chain dysfunction, together with increased deposition of cholesterol and cholesteryl esters, are hallmarks of atherosclerosis. This study investigated the role of mitochondrial function in regulation of macrophage cholesterol efflux to apolipoprotein A-I, by the addition of established pharmacological modulators of mitochondrial function. Methods Murine RAW 264.7 macrophages were treated with a range of concentrations of resveratrol, antimycin, dinitrophenol, nigericin and oligomycin, and changes in viability, cytotoxicity, membrane potential and ATP, compared with efflux of [3H]cholesterol to apolipoprotein (apo A-I. The effect of oligomycin treatment on expression of genes implicated in macrophage cholesterol homeostasis were determined by quantitative polymerase chain reaction, and immunoblotting, relative to the housekeeping enzyme, Gapdh, and combined with studies of this molecule on cholesterol esterification, de novo lipid biosynthesis, and induction of apoptosis. Significant differences were determined using analysis of variance, and Dunnett’s or Bonferroni post t-tests, as appropriate. Results The positive control, resveratrol (24 h, significantly enhanced cholesterol efflux to apoA-I at concentrations ≥30 μM. By contrast, cholesterol efflux to apoA-I was significantly inhibited by nigericin (45%; ppAbca1 mRNA. Oligomycin treatment did not affect cholesterol biosynthesis, but significantly inhibited cholesterol esterification following exposure to acetylated LDL, and induced apoptosis at ≥30 μM. Finally, oligomycin induced the expression of genes implicated in both cholesterol efflux (Abca1, Abcg4, Stard1 and cholesterol biosynthesis (Hmgr, Mvk, Scap, Srebf2, indicating profound dysregulation of cholesterol homeostasis. Conclusions Acute loss of mitochondrial function, and in particular Δψm, reduces

  19. Increased HDL Size and Enhanced Apo A-I Catabolic Rates Are Associated With Doxorubicin-Induced Proteinuria in New Zealand White Rabbits. (United States)

    López-Olmos, Victoria; Carreón-Torres, Elizabeth; Luna-Luna, María; Flores-Castillo, Cristobal; Martínez-Ramírez, Miriam; Bautista-Pérez, Rocío; Franco, Martha; Sandoval-Zárate, Julio; Roldán, Francisco-Javier; Aranda-Fraustro, Alberto; Soria-Castro, Elizabeth; Muñoz-Vega, Mónica; Fragoso, José-Manuel; Vargas-Alarcón, Gilberto; Pérez-Méndez, Oscar


    The catabolism and structure of high-density lipoproteins (HDL) may be the determining factor of their atheroprotective properties. To better understand the role of the kidney in HDL catabolism, here we characterized HDL subclasses and the catabolic rates of apo A-I in a rabbit model of proteinuria. Proteinuria was induced by intravenous administration of doxorubicin in New Zealand white rabbits (n = 10). HDL size and HDL subclass lipids were assessed by electrophoresis of the isolated lipoproteins. The catabolic rate of HDL-apo A-I was evaluated by exogenous radiolabelling with iodine-131. Doxorubicin induced significant proteinuria after 4 weeks (4.47 ± 0.55 vs. 0.30 ± 0.02 g/L of protein in urine, P HDL2b augmented significantly during proteinuria, whereas small HDL3b and HDL3c decreased compared to basal conditions. HDL2b, HDL2a, and HDL3a subclasses were enriched with triacylglycerols in proteinuric animals as determined by the triacylglycerol-to-phospholipid ratio; the cholesterol content in HDL subclasses remained unchanged. The fractional catabolic rate (FCR) of [(131)I]-apo A-I in the proteinuric rabbits was faster (FCR = 0.036 h(-1)) compared to control rabbits group (FCR = 0.026 h(-1), P HDL, whereas PON-1 activity increased in proteinuric rabbits. Proteinuria was associated with an increased number of large HDL2b particles and a decreased number of small HDL3b and 3c. Proteinuria was also connected to an alteration in HDL subclass lipids, apolipoprotein content of HDL, high paraoxonase-1 activity, and a rise in the fractional catabolic rate of the [(131)I]-apo A-I.

  20. Exposure to CB-153 and p,p&apos;-DDE and human sperm chromatin integrity

    Energy Technology Data Exchange (ETDEWEB)

    Rignell-Hydbom, A.; Rylander, L.; Joensson, B.A.G.; Hagmar, L. [Dept. of Occupational and Environmental Medicine, Lund Univ. Hospital (Sweden); Giwercman, A. [Fertility Centre, Malmoe Univ. hospital (Sweden); Spano, M. [Section of Toxicology and Biomedical Sciences, ENEA Casaccia Research Centre, Rome (Italy)


    In Sweden, the consumption of fatty fish from the Baltic Sea (off the Swedish east coast) is the single most important source of exposure to persistent organochlorine pollutants (POPs). Fishermen from the east coast have averagely higher plasma levels of polychlorinated biphenyls (PCBs) and total POP derived TEQ in plasma than both west coast fishermen and men from the general population. Dichlorodiphenyl dichloroethene (p,p&apos;-DDE), a relevant biomarker for POP is still present in relatively high serum concentrations in men consuming fish from the Baltic Sea. Several studies have shown that POPs are capable of interfering with reproductive and endocrine function in animals. Human studies have shown that exposure to PCBs and polychlorinated dibenzofurans (PCDFs) has a negative effect on male reproductive function, and especially sperm motility seems vulnerable. However, studies relating to human sperm genetic integrity are few. The aim of the study was to investigate whether exposure to POP using 2,2&apos;,4,4&apos;,5,5&apos;- hexachlorobiphenyl (CB-153) and p,p&apos;-DDE as biomarkers, are associated with sperm chromatin integrity. In order to ensure a sufficient variation in POP exposure fishermen from both the Swedish east (&apos;&apos;more exposed&apos;&apos;) and west coasts (&apos;&apos;less exposed&apos;&apos;) formed the study base.

  1. Human apolipoprotein E4 modulates the expression of Pin1, Sirtuin 1, and Presenilin 1 in brain regions of targeted replacement apoE mice. (United States)

    Lattanzio, F; Carboni, L; Carretta, D; Rimondini, R; Candeletti, S; Romualdi, P


    The apolipoprotein E4 (apoE4) allele is consistently associated with increased risk for Alzheimer's disease (AD). We investigated the molecular mechanism of this susceptibility by analyzing the levels of genes involved in AD pathogenesis in transgenic mice expressing human apoE3 or apoE4 isoforms. mRNA and protein levels of Pin1, Sirtuin 1 (Sirt1), Presenilin 1 (PS1), and pro-Brain-derived Neurotrophic Factor (BDNF) were analyzed in brain regions affected by neuropathological changes in AD. Pin1 mRNA was significantly higher in the hippocampus of apoE4 mice than in apoE3 controls, whereas lower expression was detected in the entorhinal and parietal cortices. Reduced Pin1 levels may increase neurofibrillary degeneration and amyloidogenic processes, while compensatory mechanisms may take place in the hippocampus to balance spatial memory deficits. Sirt1 levels were significantly reduced in the frontal cortex of apoE4 mice. Sirt1 reduction may hinder its protective role against the formation of plaques and tangles and diminish its anti-inflammatory actions. Sirt1 decrease may also play a role in apoE4-associated memory impairments. Moreover, in apoE4 mice PS1 mRNA levels were lower in the frontal cortex. Lower PS1 expression may hamper γ-secretase function, thus affecting amyloid precursor protein processing. Pro-BDNF mRNA levels did not differ between apoE3 and apoE4 mice in any region analyzed. This study showed dysregulated expression of Pin1, Sirt1, and PS1 genes in different cerebral areas of apoE4 mice, suggesting that these changes may play a role in the mechanism of AD vulnerability.

  2. A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD

    DEFF Research Database (Denmark)

    Fujihara, Masashi; Bartels, Emil; Nielsen, Lars B


    changes consistent with early human AMD including loss of basal infoldings and accumulation of cytoplasmic vacuoles in the RPE, and basal laminar deposits containing long-spacing collagen and heterogeneous debris in Bruch membrane of apoB100 mice. In apoB100 mice given a high-fat diet, basal linear...

  3. Inducible Apoe Gene Repair in Hypomorphic ApoE Mice Deficient in the LDL Receptor Promotes Atheroma Stabilization with a Human-like Lipoprotein Profile (United States)

    Eberlé, Delphine; Luk, Fu Sang; Kim, Roy Y.; Olivas, Victor R.; Kumar, Nikit; Posada, Jessica M.; Li, Kang; Gaudreault, Nathalie; Rapp, Joseph H.; Raffai, Robert L.


    Objective To study atherosclerosis regression in mice following plasma lipid reduction to moderately elevated apolipoprotein B (apoB)-lipoprotein levels. Approach and Results Chow-fed hypomorphic Apoe mice deficient in LDL receptor expression (Apoeh/hLdlr−/−Mx1-cre mice) develop hyperlipidemia and atherosclerosis. These mice were studied before and after inducible cre-mediated Apoe gene repair. By 1 week, induced mice displayed a 2-fold reduction in plasma cholesterol and triglyceride levels and a decrease in the non-HDL:HDL-cholesterol ratio from 87%:13% to 60%:40%. This halted atherosclerotic lesion growth and promoted macrophage loss and accumulation of thick collagen fibers for up to 8 weeks. Concomitantly, blood Ly-6Chi monocytes were decreased by 2-fold but lesional macrophage apoptosis was unchanged. The expression of several genes involved in extra-cellular matrix remodeling and cell migration were changed in lesional macrophages 1 week after Apoe gene repair. However, mRNA levels of numerous genes involved in cholesterol efflux and inflammation were not significantly changed at this time point. Conclusions Restoring apoE expression in Apoeh/hLdlr−/−Mx1-cre mice resulted in lesion stabilization in the context of a human-like ratio of non-HDL:HDL-cholesterol. Our data suggest that macrophage loss derived in part from reduced blood Ly-6Chi monocytes levels and genetic reprogramming of lesional macrophages. PMID:23788760

  4. Binding and repressive activities of apolipoprotein E3 and E4 isoforms on the human ApoD promoter. (United States)

    Levros, Louis-Charles; Labrie, Marilyne; Charfi, Cyndia; Rassart, Eric


    Apolipoprotein D (ApoD) gene expression is increased in several neurological disorders such as Alzheimer's disease (AD) and multiple sclerosis. We previously showed that transgenic mice that overexpress human ApoD show a better resistance against paraquat or OC43 coronavirus-induced neurodegeneration. Here, we identified several nuclear factors from the cortex of control and OC43-infected mice which bind a fragment of the proximal ApoD promoter in vitro. Of interest, we detected apolipoprotein E (ApoE). Human ApoE consists of three isoforms (E2, E3, and E4) with the E4 and E2 alleles representing a greater and a lower risk for developping AD, respectively. Our results show that ApoE is located in the nucleus and on the ApoD promoter in human hepatic and glioblastoma cells lines. Furthermore, overexpression of ApoE3 and ApoE4 isoforms but not ApoE2 significantly inhibited the ApoD promoter activity in U87 cells (E3/E3 genotype) cultured under normal or different stress conditions while ApoE knock-down by siRNA had a converse effect. Consistent with these results, we also demonstrated by ChIP assay that E3 and E4 isoforms, but not E2, bind the ApoD promoter. Moreover, using the Allen Brain Atlas in situ hybridization database, we observed an inverse correlation between ApoD and ApoE mRNA expression during development and in several regions of the mouse brain, notably in the cortex, hippocampus, plexus choroid, and cerebellum. This negative correlation was also observed for cortex layers IV-VI based on a new Transcriptomic Atlas of the Mouse Neocortical Layers. These findings reveal a new function for ApoE by regulating ApoD gene expression.

  5. Are Sciences Essential and Humanities Elective? Disentangling Competing Claims for Humanities&apos; Research Public Value (United States)

    Olmos-Peñuela, Julia; Benneworth, Paul; Castro-Martínez, Elena


    Recent policy discourse suggests that arts and humanities research is seen as being less useful to society than other disciplines, notably in science, technology, engineering and mathematics. The paper explores how this assumption&apos;s construction has been built and whether it is based upon an unfair prejudice: we argue for a prima facie case…

  6. Targeted overexpression of the human urotensin receptor transgene in smooth muscle cells: effect of UT antagonism in ApoE knockout mice fed with Western diet. (United States)

    Papadopoulos, Panayiota; Bousette, Nicolas; Al-Ramli, Wisam; You, Zhipeng; Behm, David J; Ohlstein, Eliot H; Harrison, Stephen M; Douglas, Stephen A; Giaid, Adel


    Urotensin II (UII) and its receptor UT are upregulated in the pathological setting of various cardiovascular diseases including atherosclerosis. However, their exact role in atherosclerosis remains to be determined. In the present study we used four strains of mice; wild-type (WT), UT(+) (a transgenic strain expressing human UT driven by the alpha-smooth muscle-specific, SM22, promoter), ApoE knockout (ko), and UT(+)/ApoE ko. All animals were fed high fat diet for 12 weeks. Western blot analysis revealed a significant increase in aortic UT expression in UT(+) relative to WT mice (PUT protein level to that of UT(+). Immunohistochemistry revealed the presence of strong expression of UT and UII proteins in the atheroma of UT(+), ApoE ko and UT(+)/ApoE ko mice, particularly in foam cells. Serum cholesterol and triglyceride levels were significantly increased in ApoE ko and in UT(+)/ApoE ko but not in UT(+) mice when compared to WT mice (PUT(+), ApoE ko and UT(+)/ApoE ko compared to WT mice (PUT receptor antagonist SB-657510A (30 microg/Kg/day gavage) for 10 weeks in a group of ApoE ko mice fed on high fat diet resulted in a significant reduction of lesion (PUT in the pathogenesis of atherosclerosis. The use of UT receptor antagonists may provide a beneficial tool in the management of this debilitating disease process.


    Institute of Scientific and Technical Information of China (English)

    Liu Enqi(刘恩岐); Shuji Kitajima; Masatoshi Morimoto


    Objective To create transgenic rabbits by microinjecting human apolipoprotein A-Ⅱ (apoA-Ⅱ) gene into one-cell embryos, to study apoA-Ⅱ gene function on plasma lipoprotein metabolism and atherosclerosis. Methods Superovulation and synchronization of estrus were induced in female Japanese White Rabbits by injecting hormone, then mating with male. After collected the fertilized eggs, the human apoA-Ⅱ gene was microinjected into the male pronucleus of eggs. The injected eggs were transferred into recipient female rabbits. Last, extract DNA from the new borns ear and determine whether the newborns were transgenic by polymerase chain reaction (PCR) or Southern blot analysis. Results A total of 822 embryos with microinjection of human apoAⅡ gene were implanted into 28 recipient rabbits. The number of surviving newborns was 37. 3 transgenic positive surviving founders were found with human apoA-Ⅱ.

  8. Regional-specific effects of ovarian hormone loss on synaptic plasticity in adult human APOE targeted replacement mice.

    Directory of Open Access Journals (Sweden)

    Rebecca C Klein

    Full Text Available The human apolipoprotein ε4 allele (APOE4 has been implicated as one of the strongest genetic risk factors associated with Alzheimer's disease (AD and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE. In the current study, female adult human APOE targeted replacement (TR mice were utilized to examine the effects of human APOE genotype and long-term ovarian hormone loss on synaptic plasticity in limbic regions by measuring dendritic spine density and electrophysiological function. No significant genotype differences were observed on any outcomes within intact mice. However, there was a significant main effect of genotype on total spine density in apical dendrites in the hippocampus, with post-hoc t-tests revealing a significant reduction in spine density in apoE3 ovariectomized (OVX mice compared to sham operated mice. There was also a significant main effect of OVX on the magnitude of LTP, with post-hoc t-tests revealing a decrease in apoE3 OVX mice relative to sham. In contrast, apoE4 OVX mice showed increased synaptic activity relative to sham. In the lateral amygdala, there was a significant increase in total spine density in apoE4 OVX mice relative to sham. This increase in spine density was consistent with a significant increase in spontaneous excitatory activity in apoE4 OVX mice. These findings suggest that ovarian hormones differentially modulate synaptic integrity in an apoE-dependent manner within brain regions that are susceptible to neurophysiological dysfunction associated with AD.

  9. Chromatofocusing of human high density lipoproteins and isolation of lipoproteins A and A-I. (United States)

    Nestruck, A C; Niedmann, P D; Wieland, H; Seidel, D


    Using chromatofocusing, a column chromatography method with an internally generated pH gradient and focusing effects, human plasma high density lipoproteins (HDL) were fractionated into six subclasses within an interval of less than 1 pH unit (pH 5.1-4.2). All fractions floated in the ultracentrifuge at density = 1.21 g X ml-1, retained a typical HDL electron micrographic morphology and as a single band, alpha-migration on agarose electrophoresis. Compositional analysis of the subclasses revealed an inverse relationship between cholesterol ester and cholesterol on a molar basis. Distinct differences in the distribution of the apolipoproteins between the fractions were found. Two of the subclasses contained only apolipoprotein A-I and were therefore considered to be two forms of the lipid-combined form of apolipoprotein A-I, i.e., lipoprotein A-I. One subclass contained only apolipoproteins A-I + A-II and was, therefore, lipoprotein A. One subclass contained apolipoproteins A-I + A-II + D, and the two remaining contained additionally apolipoproteins C and E. Lipoprotein A-I was also demonstrated after immunoabsorption of apolipoprotein A-II-containing lipoproteins from whole serum. It is suggested that this method, which allows the fractionation of HDL into subclasses with distinct differences in apolipoprotein composition, offers new avenues for the study of the structural and metabolic heterogeneity of HDL.

  10. Students&apos; Learning Strategies with Multiple Representations: Explanations of the Human Breathing Mechanism (United States)

    Won, Mihye; Yoon, Heojeong; Treagust, David F.


    The purpose of this study was to understand how students utilized multiple representations to learn and explain science concepts, in this case the human breathing mechanism. The study was conducted with Grade 11 students in a human biology class. Semistructured interviews and a two-tier diagnostic test were administered to evaluate students&apos;…

  11. Comparative Analysis of OECD Member Countries&apos; Competitive Advantage in National Human Resource Development System (United States)

    Oh, Hunseok; Choi, Yeseul; Choi, Myungweon


    The purpose of this study was to assess, evaluate, and compare the competitive advantages of the human resource development systems of advanced countries. The Global Human Resource Development Index was utilized for this study, since it has been validated through an expert panel&apos;s content review and analytic hierarchy process. Using a sample…

  12. Statement by the Federal Environmental Office on nickel. Position of the &apos;'Human Biomonitoring Commission&apos;&apos; of the Federal Environmental Office; Bekanntmachung des Umweltbundesamtes &apos;Nickel&apos;. Stellungnahme der Kommission &apos;'Human-Biomonitoring'&apos; des Umweltbundesamtes

    Energy Technology Data Exchange (ETDEWEB)



    One of the focal areas of interest in environmental medicine are the sensitising and cancerogenic effects of nickel. There is no means within the realm of environmental medicine, nor in particular of biomonitoring, of either quantifying or preventing these two types of effects. However, there is evidence that even average rates of nickel uptake via food and water suffice to cause an aggravation or recurrence of nickel-induced contact eczemas. Nickel uptake rates in western industrial countries appear to be fairly uniform and roughly equal to nickel elimination via the urine. According to the present database 3 {mu}g appears to be a tenable reference value. Urinary nickel excretion levels in patients suffering from generalised nickel-induced contact eczemas who respond positively to epicutaneous tests could serve as an indicator of elevated nickel uptake via food or water. In the same way human biomonitoring could serve to determine the efficacy of nickel reducing dietary measures. [German] Im Bereich der Umweltmedizin steht die sensibilisierende und die krebserzeugende Wirkung von Nickel im Vordergrund des Interesses. Beide Wirkungen koennen im Bereich der Umweltmedizin durch ein Human-Biomonitoring weder quantifiziert noch verhindert werden. Es gibt jedoch Hinweise darauf, dass bereits die ueblicherweise ueber Nahrung und/oder Trinkwasser aufgenommene Nickelmenge zu einer Verschlimmerung oder zu einem Wiederauftreten von nickelbedingten Kontaktekzemen fuehren koennte. In den westlichen Industrielaendern scheint die Nickelaufnahme relative gleichfoermig zu sein und zu einer vergleichbaren Nickelausscheidung im Harn zu fuehren. Nach der aktuellen Datenlage kann 3 {mu}g/l als Referenzwert verwendet werden. Bei Patienten, die an generalisierten nickelbedingten Ekzemen leiden und die im Epikutantest positv auf Nickel reagieren, koennen anhand der Nickelausscheidung im Urin Hinweise auf eine moeglicherweise vermehrte Nickelaufnahme aus der Nahrung oder aus dem

  13. FISH &apos;N&apos; Chips : a single cell genomic analyzer for the human microbiome.

    Energy Technology Data Exchange (ETDEWEB)

    Light, Yooli Kim; Perroud, Thomas D.; Hugenholtz, Philip (Joint Genome Institute, Walnut Creek, CA); Meagher, Robert J.; Singh, Anup K.; Malamud, Daniel (New York University, New York, NY); Saxena, Deepak (New York University, New York, NY); Liu, Peng


    Uncultivable microorganisms likely play significant roles in the ecology within the human body, with subtle but important implications for human health. Focusing on the oral microbiome, we are developing a processor for targeted isolation of individual microbial cells, facilitating whole-genome analysis without the need for isolation of pure cultures. The processor consists of three microfluidic modules: identification based on 16S rRNA fluorescence in situ hybridization (FISH), fluorescence-based sorting, and encapsulation of individual selected cells into small droplets for whole genome amplification. We present here a technique for performing microscale FISH and flow cytometry, as a prelude to single cell sorting.

  14. &apos;Ye Olde Hot Aire&apos; : reporting on human contributions to climate change in the UK tabloid press

    Energy Technology Data Exchange (ETDEWEB)

    Boykoff, Maxwell T; Mansfield, Maria [Environmental Change Institute, University of Oxford, South Parks Road, Oxford OX1 3QY (United Kingdom)], E-mail:, E-mail:


    This letter explores daily print media coverage of climate change in four United Kingdom (UK) tabloid newspapers: The Sun (and News of the World), Daily Mail (and Mail on Sunday), the Daily Express (and Sunday Express), and the Mirror (and Sunday Mirror). Through examinations of content in articles over the last seven years (2000-2006), triangulated with semi-structured interviews of journalists and editors, the study finds that UK tabloid coverage significantly diverged from the scientific consensus that humans contribute to climate change. Moreover, there was no consistent increase in the percentage of accurate coverage throughout the period of analysis and across all tabloid newspapers, and these findings are not consistent with recent trends documented in United States and UK &apos;prestige press&apos; or broadsheet newspaper reporting. Findings from interviews indicate that inaccurate reporting may be linked to the lack of specialist journalists in the tabloid press. This study therefore contributes to wider discussions of socio-economic inequality, media and the environment. Looking to newspapers that are consumed by typically working class readership, this article contributes to ongoing investigations related to what media representations mean for ongoing science-policy interactions as well as potentialities for public engagement.

  15. University Students&apos; Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey (United States)

    Koç, Zeliha


    Objectives: The current descriptive study aimed to determine university students&apos; knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…

  16. Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element (United States)

    Claudel, Thierry; Sturm, Ekkehard; Duez, Hélène; Torra, Inés Pineda; Sirvent, Audrey; Kosykh, Vladimir; Fruchart, Jean-Charles; Dallongeville, Jean; Hum, Dean W.; Kuipers, Folkert; Staels, Bart


    Serum levels of HDL are inversely correlated with the risk of coronary heart disease. The anti-atherogenic effect of HDL is partially mediated by its major protein constituent apoA-I. In this study, we identify bile acids that are activators of the nuclear receptor farnesoid X receptor (FXR) as negative regulators of human apoA-I expression. Intrahepatocellular accumulation of bile acids, as seen in patients with progressive familial intrahepatic cholestasis and biliary atresia, was associated with diminished apoA-I serum levels. In human apoA-I transgenic mice, treatment with the FXR agonist taurocholic acid strongly decreased serum concentrations and liver mRNA levels of human apoA-I, which was associated with reduced serum HDL levels. Incubation of human primary hepatocytes and hepatoblastoma HepG2 cells with bile acids resulted in a dose-dependent downregulation of apoA-I expression. Promoter mutation analysis and gel-shift experiments in HepG2 cells demonstrated that bile acid–activated FXR decreases human apoA-I promoter activity by a negative FXR response element mapped to the C site. FXR bound this site and repressed transcription in a manner independent of retinoid X receptor. The nonsteroidal synthetic FXR agonist GW4064 likewise decreased apoA-I mRNA levels and promoter activity in HepG2 cells. PMID:11927623

  17. Electromagnetic field effect simulation over a realistic pixel ed phantom human&apos;s brain

    Energy Technology Data Exchange (ETDEWEB)

    Rojas, R.; Calderon, J. A.; Rivera, T. [IPN, Centro de Investigacion en Ciencia Aplicada y Tecnologia Avanzada, Calz. Legaria No. 694, Col. Irrigacion, 11500 Mexico D. F. (Mexico); Azorin, J., E-mail: [Universidad Autonoma Metropolitana, Unidad Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, 09340 Mexico D. F. (Mexico)


    The exposition to different types of electromagnetic radiations can produce damages and injures on the people&apos;s tissues. The scientist, spend time and resources studying the effects of electromagnetic fields over the organs. Particularly in medical areas, the specialist in imaging methodologies and radiological treatment, are very worried about no injure there patient. Determination of matter radiation interaction, can be experimental or theoretical is not an easy task anyway. At first case, is not possible make measures inside the patient, then the experimental procedure consist in make measures in human&apos;s dummy, however, is not possible see deformations of electromagnetic fields due the organs presence. In the second case, is necessary solve, the Maxwell&apos;s equations with the electromagnetic field, crossing a lot of organs and tissues with different electric and magnetic properties each one. One alternative for theoretical solution, is make a computational simulation, however, this option, require an enormous quantity of memory and large computational times. Then, the most simulations are making in 2 dimensional or in 3 dimensional although using human models approximations, build ed with basic geometrical figures, like spheres, cylinders, ellipsoids, etc. Obviously this models just lets obtain a coarse solution of the actually situation. In this work, we propose a novel methodology to build a realistic pixel ed phantom of human&apos;s organs, and solve the Maxwell&apos;s equations over this models, evidently, the solutions are more approximated to the real behaviour. Additionally, there models results optimized when they are discretized and the finite element method is used to calculate the electromagnetic field and the induced currents. (Author)

  18. LXR agonist increases apoE secretion from HepG2 spheroid, together with an increased production of VLDL and apoE-rich large HDL

    Directory of Open Access Journals (Sweden)

    Koike Kazuhiko


    Full Text Available Abstract Background The physiological regulation of hepatic apoE gene has not been clarified, although the expression of apoE in adipocytes and macrophages has been known to be regulated by LXR. Methods and Results We investigated the effect of TO901317, a LXR agonist, on hepatic apoE production utilizing HepG2 cells cultured in spheroid form, known to be more differentiated than HepG2 cells in monolayer culture. Spheroid HepG2 cells were prepared in alginate-beads. The secretions of albumin, apoE and apoA-I from spheroid HepG2 cells were significantly increased compared to those from monolayer HepG2 cells, and these increases were accompanied by increased mRNA levels of apoE and apoA-I. Several nuclear receptors including LXRα also became abundant in nuclear fractions in spheroid HepG2 cells. Treatment with TO901317 significantly increased apoE protein secretion from spheroid HepG2 cells, which was also associated with the increased expression of apoE mRNA. Separation of the media with FPLC revealed that the production of apoE-rich large HDL particles were enhanced even at low concentration of TO901317, and at higher concentration of TO901317, production of VLDL particles increased as well. Conclusions LXR activation enhanced the expression of hepatic apoE, together with the alteration of lipoprotein particles produced from the differentiated hepatocyte-derived cells. HepG2 spheroids might serve as a good model of well-differentiated human hepatocytes for future investigations of hepatic lipid metabolism.

  19. SAA is Found on ApoB-Containing Lipoproteins in Obese Diabetic Humans


    Jahangiri, Anisa; Wilson, Patricia G.; Hou, Tianfei; Brown, Aparna; King, Victoria L.; Tannock, Lisa R.


    In murine models of obesity/diabetes there is an increase in plasma SAA levels along with redistribution of SAA from high density lipoprotein (HDL) to apo-B containing lipoprotein particles, namely low density lipoprotein (LDL) and very low density lipoprotein (VLDL). The goal of this study was to determine if obesity is associated with similar SAA lipoprotein redistribution in humans. Three groups of obese individuals were recruited from a weight loss clinic: healthy obese (n=14), metabolic ...

  20. Serum amyloid A is found on ApoB-containing lipoproteins in obese humans with diabetes. (United States)

    Jahangiri, Anisa; Wilson, Patricia G; Hou, Tianfei; Brown, Aparna; King, Victoria L; Tannock, Lisa R


    In murine models of obesity/diabetes, there is an increase in plasma serum amyloid A (SAA) levels along with redistribution of SAA from high-density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoprotein particles, namely, low-density lipoprotein and very low-density lipoprotein. The goal of this study was to determine if obesity is associated with similar SAA lipoprotein redistribution in humans. Three groups of obese individuals were recruited from a weight loss clinic: healthy obese (n = 14), metabolic syndrome (MetS) obese (n = 8), and obese with type 2 diabetes (n = 6). Plasma was separated into lipoprotein fractions by fast protein liquid chromatography, and SAA was measured in lipid fractions using enzyme-linked immunosorbent assay and Western blotting. Only the obese diabetic group had SAA detectable in apoB-containing lipoproteins, and SAA reverted back to HDL with active weight loss. In human subjects, SAA is found in apoB-containing lipoprotein particles only in obese subjects with type 2 diabetes, but not in healthy obese or obese subjects with MetS. Copyright © 2012 The Obesity Society.

  1. Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn&apos;s Disease

    Energy Technology Data Exchange (ETDEWEB)

    Erickson, Alison L [ORNL; Cantarel, Brandi [University of Maryland School of Medicine, The, Baltimore, MD; Lamendella, Regina [Lawrence Berkeley National Laboratory (LBNL); Darzi, Youssef [Vrije Universiteit Brussel, Brussels, Belgium; Mongodin, Emmanuel [University of Maryland School of Medicine, The, Baltimore, MD; Pan, Chongle [ORNL; Shah, Manesh B [ORNL; Halfvarsson, J [Orebro University Hospital, Orebro, Sweden; Tysk, C [Orebro University Hospital, Orebro, Sweden; Henrissat, Bernard [Universite d' Aix-Marseille I & II; Raes, Jeroen [Vrije Universiteit Brussel, Brussels, Belgium; Verberkmoes, Nathan C [ORNL; Fraser-Liggett, C [University of Maryland; Hettich, Robert {Bob} L [ORNL; Jansson, Janet [Lawrence Berkeley National Laboratory (LBNL)


    Crohn&apos;s disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn&apos;s disease and aids in identification of novel diagnostic targets and disease specific biomarkers.

  2. Lytic efficacy of apoli protein E2 (ApoE2) and recombinant tissue plasminogen activator (rt-PA) treatment with 120 kHz ultrasound in an in-vitro human clot model (United States)

    Meunier, Jason M.; Cheng, Jason Y.; Clark, Joseph F.; Shaw, George J.


    Currently, the only FDA approved therapy for acute ischemic stroke is recombinant tissue plasminogen activator (rt-PA). However rt-PA has substantial side effects such as hemorrhage. This has led to interest in other potential therapies. For example, ultrasound (US) increases the lytic efficacy of rt-PA. Also, apolipoprotein E2 (ApoE2) increases rt-PA activity. This suggests combining US, ApoE2 and rt-PA to improve thrombolysis, but the efficacy is not known. Here, the lytic efficacy of apoE2, rt-PA and 120 kHz US is measured in a human clot model. Whole blood was obtained from volunteers, after local institutional approval. Clots were formed in 1.7 mm micropipettes, and placed in a water tank that allowed microscopic video imaging during US and thrombolytic exposure. Clots were treated with rt-PA ([rt-PA]=3.15 μg/ml), rt-PA and apoE2 ([apoE2]=9.8 μg/ml), or rt-PA, apoE2 and 120 kHz US (0.35 MPa, PRF=1667 Hz, 80% duty cycle) for 15 min at 37°C in human plasma. Clot lysis was visually recorded and the lysis depth (LD) determined from these data using an image analysis algorithm. LD was linear with time for all treatments (R2>=0.81), allowing the determination of a lytic rate (LR). LR was found to be 0.35+/-0.03, 1.55+/-0.11, and 0.75+/-0.04 μm/min for the rt-PA, rt-PA and apoE2, and US treated groups respectively. The thrombolytic efficacy of rt-PA is enhanced by ApoE2. The interaction of 120 kHz with apoE2 and rt-PA showed a reduced lytic efficacy compared with rt-PA and apoE2 treatment alone. It is possible that US interferes with the ApoE2-mediated activation of rt-PA.

  3. How Can We Assess and Evaluate the Competitive Advantage of a Country&apos;s Human Resource Development System? (United States)

    Oh, Hunseok; Ryu, Hyue-Hyun; Choi, Myungweon


    The purpose of this study was to develop an index to assess and evaluate the competitive advantage of a country&apos;s human resource development system. Based on an extensive literature review, a theoretical model of a human resource development system at the national level (named National Human Resource Development: NHRD) was constructed. The…

  4. How Can We Assess and Evaluate the Competitive Advantage of a Country&apos;s Human Resource Development System? (United States)

    Oh, Hunseok; Ryu, Hyue-Hyun; Choi, Myungweon


    The purpose of this study was to develop an index to assess and evaluate the competitive advantage of a country&apos;s human resource development system. Based on an extensive literature review, a theoretical model of a human resource development system at the national level (named National Human Resource Development: NHRD) was constructed. The…

  5. Crystal Structures of Human Dipeptidyl Peptidase Ⅳ in its Apo and Diprotin B-complexed Forms

    Institute of Scientific and Technical Information of China (English)

    Hajime HIRAMATSU; Kiyoshi KYONO; Atsushi YAMAMOTO; Kazuhiko SAEKI; Hideaki SHIMA; Shigeru SUGIYAMA; Koji INAKA; Ryo SHIMIZU


    Dipeptidyl peptidase Ⅳ (DPPIV), which belongs to the prolyl oligopeptidase family of serine proteases, is known to have a variety of regulatory biological functions and has been shown to be implicated in type 2 diabetes. It is therefore important to develop selective human DPPIV (hDPPIV) inhibitors. In this study, we determined the crystal structure of apo hDPPIV at 1.9 (A) resolution. Our high-resolution crystal structure of apo hDPPIV revealed the presence of sodium ion and glycerol molecules at the active site. In order to elucidate the hDPPIV binding mode and substrate specificity, we determined the crystal structure of hDPPIV-diprotin B (Val-Pro-Leu) complex at 2.1 (A) resolution, and clarified the difference in binding mode between diprotin B and diprotin A (Ile-Pro-Ile) into the active site of hDPPIV. Comparison between our crystal structures and the reported apo hDPPIV structures revealed that positively charged functional groups and conserved water molecules contributed to the interaction of ligands with hDPPIV. These results are useful for the design of potent hDPPIV inhibitors.

  6. The Relationship between Human Operators&apos; Psycho-physiological Condition and Human Errors in Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Arryum; Jang, Inseok; Kang, Hyungook; Seong, Poonghyun [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)


    The safe operation of nuclear power plants (NPPs) is substantially dependent on the performance of the human operators who operate the systems. In this environment, human errors caused by inappropriate performance of operator have been considered to be critical since it may lead serious problems in the safety-critical plants. In order to provide meaningful insights to prevent human errors and enhance the human performance, operators&apos; physiological conditions such as stress and workload have been investigated. Physiological measurements were considered as reliable tools to assess the stress and workload. T. Q. Tran et al. and J. B. Brooking et al pointed out that operators&apos; workload can be assessed using eye tracking, galvanic skin response, electroencephalograms (EEGs), heart rate, respiration and other measurements. The purpose of this study is to investigate the effect of the human operators&apos; tense level and knowledge level to the number of human errors. For this study, the experiments were conducted in the mimic of the main control rooms (MCR) in NPP. It utilized the compact nuclear simulator (CNS) which is modeled based on the three loop Pressurized Water Reactor, 993MWe, Kori unit 3 and 4 in Korea and the subjects were asked to follow the tasks described in the emergency operating procedures (EOP). During the simulation, three kinds of physiological measurement were utilized; Electrocardiogram (ECG), EEG and nose temperature. Also, subjects were divided into three groups based on their knowledge of the plant operation. The result shows that subjects who are tense make fewer errors. In addition, subjects who are in higher knowledge level tend to be tense and make fewer errors. For the ECG data, subjects who make fewer human errors tend to be located in higher tense level area of high SNS activity and low PSNS activity. The results of EEG data are also similar to ECG result. Beta power ratio of subjects who make fewer errors was higher. Since beta

  7. Indonesia&apos;s present status and needs of human resource development in nuclear field

    Energy Technology Data Exchange (ETDEWEB)

    Ruslan, Jeni; Sagala, F.P. [National Nuclear Energy Agency of Indonesia (Indonesia)


    BATAN, started out as a governmental committee established in 1954, has a new organizational structure, based on Presidential Decree of 1998. BATAN has developed its researches in almost practically all-nuclear fields. The situation in Indonesia has been much influenced by the economic crisis, which still being faced by Indonesia. BATAN&apos;s strategic planning is described in four areas, those are: 1. Basic human needs, 2. Energy, natural resources and environment, 3. Industry, 4. Socio-cultural and institution. Priority has been given to fulfill, as well as to promote agriculture, health and the industry related to people&apos;s welfare, which may develop and improve the immediate needs of the people. In the meantime, we have made considerable investments in manpower development in anticipation of the introduction of nuclear power. BATAN, as of September 1999, has 3889 employees, 26 % of them have bachelor degree, 6 % hold master degrees, and only 2% hold doctoral degree, a total of 34 % employees with university education. Others 11 % have either non-vocational or vocational education beyond High School. The rest of 55 % have high school education or lower, they are administrative clerks (25 %) or technicians (30 %). In the human resources development, BATAN&apos;s Education and Training Center, in collaboration with some universities and other national/international institutions, is managing education and training programs for employees. To date, there are 43 BATAN employees studying in various universities in Japan, while another 42 employees are studying in six different countries. Research and Development that have more direct impact to the community will become a priority in the coming years. Without undermining the importance of basic research in advanced fields, we will expect to have more research on application to optimize utilization of research reactors and related facilities for the benefit of both the energy and non-energy sectors. (Tanaka, Y.)

  8. Cloning and Expression of Apolipoprotein E3 and Its Variant apoE2 and apoE4

    Institute of Scientific and Technical Information of China (English)


    In order to obtain three isoforms of apolipoprotein E (apoE), the cDNA encoding apoE3 was obtained by RT-PCR from normal human liver tissue. Site-directed mutagenesis was used to obtain the cDNAs encoding apoE2 and apoE4 isoforms. The 3 cDNAs were subcloned into vector pGEM-3Z and verified by DNA sequencing. The expression recombinant which can express the target protein as a (His) 6-tagged fusion was constructed by subcloning apoE cDNA into vector pT7-PL. The purified proteins were gained by Ni-NTA column. The SDS-PAGE results revealed the 6 His fusion proteins (apoE2, apoE3 and apoE4) were correctly expressed and purified successfully.

  9. ApoE isoform-dependent changes in hippocampal synaptic function

    Directory of Open Access Journals (Sweden)

    Sullivan Patrick M


    Full Text Available Abstract The lipoprotein receptor system in the hippocampus is intimately involved in the modulation of synaptic transmission and plasticity. The association of specific apoE isoform expression with human neurodegenerative disorders has focused attention on the role of these apoE isoforms in lipoprotein receptor-dependent synaptic modulation. In the present study, we used the apoE2, apoE3 and apoE4 targeted replacement (TR mice along with recombinant human apoE isoforms to determine the role of apoE isoforms in hippocampus area CA1 synaptic function. While synaptic transmission is unaffected by apoE isoform, long-term potentiation (LTP is significantly enhanced in apoE4 TR mice versus apoE2 TR mice. ApoE isoform-dependent differences in LTP induction require NMDA-receptor function, and apoE isoform expression alters activation of both ERK and JNK signal transduction. Acute application of specific apoE isoforms also alters LTP induction while decreasing NMDA-receptor mediated field potentials. Furthermore, acute apoE isoform application does not have the same effects on ERK and JNK activation. These findings demonstrate specific, isoform-dependent effects of human apoE isoforms on adult hippocampus synaptic plasticity and highlight mechanistic differences between chronic apoE isoform expression and acute apoE isoform exposure.

  10. The apo E/apo CIII molar ratio affects removal of cholesterol ester from modified human lipoproteins injected into cebus monkeys. (United States)

    Stephan, Z F; Gibson, J C; Hayes, K C


    The removal of postprandial (PP) and postabsorptive (PA) human LDL and HDL cholesterol was examined in cebus monkeys (Cebus albifrons) following in vitro labelling of these lipoproteins by 3H-cholesterol in the presence or absence of DTNB. The removal of LDL cholesteryl ester was 3.5 and 2 times greater than that of HDL in male and female monkeys, respectively. Incubation with DTNB reduced cholesteryl ester removal by 45 and 52% for LDL and HDL, respectively. Cholesteryl ester from PA lipoproteins was removed 80% faster than that PP particles only when plasma was incubated without DTNB. Cholesterol removal from these lipoproteins was positively (r = 0.941) and significantly (P less than 0.001) correlated with the molar apo E/apo CIII ratio. The data suggest that density of lipoproteins was less important than their apoprotein composition in dictating their removal from circulation.

  11. &apos;Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans

    Energy Technology Data Exchange (ETDEWEB)

    Jetten, Marlon J.A.; Gaj, Stan [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Ruiz-Aracama, Ainhoa [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Kok, Theo M. de [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Delft, Joost H.M. van, E-mail: [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Lommen, Arjen [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Someren, Eugene P. van [Research Group Microbiology and Systems Biology, TNO, PO Box 360 3700 AJ Zeist (Netherlands); Jennen, Danyel G.J.; Claessen, Sandra M. [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Peijnenburg, Ad A.C.M. [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Stierum, Rob H. [Research Group Microbiology and Systems Biology, TNO, PO Box 360 3700 AJ Zeist (Netherlands); Kleinjans, Jos C.S. [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands)


    Acetaminophen is the primary cause of acute liver toxicity in Europe/USA, which led the FDA to reconsider recommendations concerning safe acetaminophen dosage/use. Unfortunately, the current tests for liver toxicity are no ideal predictive markers for liver injury, i.e. they only measure acetaminophen exposure after profound liver toxicity has already occurred. Furthermore, these tests do not provide mechanistic information. Here, &apos;omics techniques (global analysis of metabolomic/gene-expression responses) may provide additional insight. To better understand acetaminophen-induced responses at low doses, we evaluated the effects of (sub-)therapeutic acetaminophen doses on metabolite formation and global gene-expression changes (including, for the first time, full-genome human miRNA expression changes) in blood/urine samples from healthy human volunteers. Many known and several new acetaminophen-metabolites were detected, in particular in relation to hepatotoxicity-linked, oxidative metabolism of acetaminophen. Transcriptomic changes indicated immune-modulating effects (2 g dose) and oxidative stress responses (4 g dose). For the first time, effects of acetaminophen on full-genome human miRNA expression have been considered and confirmed the findings on mRNA level. &apos;Omics techniques outperformed clinical chemistry tests and revealed novel response pathways to acetaminophen in humans. Although no definitive conclusion about potential immunotoxic effects of acetaminophen can be drawn from this study, there are clear indications that the immune system is triggered even after intake of low doses of acetaminophen. Also, oxidative stress-related gene responses, similar to those seen after high dose acetaminophen exposure, suggest the occurrence of possible pre-toxic effects of therapeutic acetaminophen doses. Possibly, these effects are related to dose-dependent increases in levels of hepatotoxicity-related metabolites. -- Highlights: ► &apos;Omics techniques

  12. The Effect of a High-Fat Diet on Brain Plasticity, Inflammation and Cognition in Female ApoE4-Knockin and ApoE-Knockout Mice

    NARCIS (Netherlands)

    Janssen, C.I.F.; Jansen, D.; Mutsaers, M.P.; Dederen, P.J.W.C.; Geenen, B.; Mulder, M.T.; Kiliaan, A.J.


    Apolipoprotein E4 (ApoE4), one of three common isoforms of ApoE, is a major risk factor for late-onset Alzheimer disease (AD). ApoE-deficient mice, as well as mice expressing human ApoE4, display impaired learning and memory functions and signs of neurodegeneration. Moreover, ApoE protects against

  13. The effect of a high-fat diet on brain plasticity, inflammation and cognition in female ApoE4-knockin and ApoE-knockout mice

    NARCIS (Netherlands)

    C.I.F. Janssen (Carola); D. Jansen (Diane); M.P.C. Mutsaers (Martina); J. Dederen (Jos); B. Geenen (Bram); M.T. Mulder (Monique); A.J. Kiliaan Kiliaan (Amanda J.)


    textabstractApolipoprotein E4 (ApoE4), one of three common isoforms of ApoE, is a major risk factor for late-onset Alzheimer disease (AD). ApoE-deficient mice, as well as mice expressing human ApoE4, display impaired learning and memory functions and signs of neurodegeneration. Moreover, ApoE

  14. The effect of a high-fat diet on brain plasticity, inflammation and cognition in female ApoE4-knockin and ApoE-knockout mice

    NARCIS (Netherlands)

    C.I.F. Janssen (Carola); D. Jansen (Diane); M.P.C. Mutsaers (Martina); J. Dederen (Jos); B. Geenen (Bram); M. Mulder (Monique); A.J. Kiliaan Kiliaan (Amanda J.)


    textabstractApolipoprotein E4 (ApoE4), one of three common isoforms of ApoE, is a major risk factor for late-onset Alzheimer disease (AD). ApoE-deficient mice, as well as mice expressing human ApoE4, display impaired learning and memory functions and signs of neurodegeneration. Moreover, ApoE protec

  15. Interaction of vanadium(IV) with human serum apo-transferrin. (United States)

    Mehtab, Sameena; Gonçalves, Gisela; Roy, Somnath; Tomaz, Ana Isabel; Santos-Silva, Teresa; Santos, Marino F A; Romão, Maria J; Jakusch, Tamás; Kiss, Tamás; Pessoa, João Costa


    The interaction of V(IV)O-salts as well as of a few V(IV)O(carrier)n complexes with human serum transferrin (hTF) is studied focusing on the determination of the nature and stoichiometry of the binding of V(IV)O(2+) to hTF, as well as whether the conformation of hTF upon binding to V(IV)O(2+) or to its complexes is changed. Circular dichroism (CD) spectra measured for solutions containing V(IV)O(2+) and apo-hTF, and V(IV)O-maltol and apo-hTF, clearly indicate that hTF-V(IV)O-maltol ternary species form with a V(IV)O:maltol stoichiometry of 1:1. For V(IV)O salts and several V(IV)O(carrier)n complexes (carrier ligand=maltolato, dhp, picolinato and dipicolinato) (Hdhp=1,2-dimethyl-3-hydroxy-4-pyridinone) the maximum number of V(IV)O(2+) bound per mole of hTF is determined to be ~2 or lower in all cases. The binding of V(IV)O to apo-hTF most certainly involves several amino acid residues of the Fe-binding site, and as concluded by urea gel electrophoresis experiments, the formation of (V(IV)O)2hTF species may occur with the closing of the hTF conformation as is the case in (Fe(III))2hTF, which is an essential feature for the transferrin receptor recognition. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Lipid-binding properties of human ApoD and Lazarillo-related lipocalins: functional implications for cell differentiation. (United States)

    Ruiz, Mario; Sanchez, Diego; Correnti, Colin; Strong, Roland K; Ganfornina, Maria D


    Lipocalins are a family of proteins characterized by a conserved eight-stranded β-barrel structure with a ligand-binding pocket. They perform a wide range of biological functions and this functional multiplicity must relate to the lipid partner involved. Apolipoprotein D (ApoD) and its insect homologues, Lazarillo (Laz) and neural Lazarillo (NLaz), share common ancestral functions like longevity, stress resistance and lipid metabolism regulation, coexisting with very specialized functions, like courtship behavior. Using tryptophan fluorescence titration, we screened the binding of 15 potential lipid partners for NLaz, ApoD and Laz and uncovered several novel ligands with apparent dissociation constants in the low micromolar range. Retinoic acid (RA), retinol, fatty acids and sphingomyelin are shared ligands. Sterols, however, showed a species-specific binding pattern: cholesterol did not show strong binding to human ApoD, whereas NLaz and Laz did bind ergosterol. Among the lipocalin-specific ligands, we found that ApoD selectively binds the endocannabinoid anandamide but not 2-acylglycerol, and that NLaz binds the pheromone 7-tricosene, but not 7,11-heptacosadiene or 11-cis-vaccenyl acetate. To test the functional relevance of lipocalin ligand binding at the cellular level, we analyzed the effect of ApoD, Laz and NLaz preloaded with RA on neuronal differentiation. Our results show that ApoD is necessary and sufficient to allow for RA differentiating activity. Both human ApoD and Drosophila NLaz successfully deliver RA to immature neurons, driving neurite outgrowth. We conclude that ApoD, NLaz and Laz bind selectively to a different but overlapping set of lipid ligands. This multispecificity can explain their varied physiological functions.

  17. Calibration Human Voxel Phantoms for In Vivo Measurement of &apos;&apos;241 Am in Bone at the Whole Body Counter Facility of CIEMAT

    Energy Technology Data Exchange (ETDEWEB)

    Moraleda, M.; Lopez, M. A.; Gomez Ros, J. M.; Navarro, T.; Navarro, J. F.


    The Whole Body Counting facility of CIEMAT is capable of carrying out In-Vivo measurements of radionuclides emitting X-rays and low energy gamma radiation internally deposited in the body. The system to use for this purpose consists of flour Low energy Germanium (LeGe) Camberra detectors working in the energy range from 10 to 1000 keV. Physical phantoms with a known contamination in the organ of interest are normally used for the calibration of the LEGe detection system. In this document we present a calibration method using the Monte Carlo technique (MCNP4C) over a voxel phantom obtained from a computerized tomography of a real human head. The phantom consists of 104017 (43x59x41) cubic voxels, 4 mn on each side, os specific tissues, but for this simulation only two types are taken into account: adipose tissue and hard bone. The skull is supposed to be contaminated with &apos;&apos;241 Am and the trajectories of the photons are simulated till they reach the germanium detectors. The detectors were also simulated in detail to obtain a good agreement with the reality. In order to verify the accuracy of this procedure to reproduce the experiments, the MCNP results are compared with laboratory measurements of a head phantom simulating an internal contamination of 1000 Bq of &apos;&apos;241 Am deposited in bone. Different relative positions source-detector were tried to look for the best countring geometry for measurement of a contaminated skull. Efficiency values are obtained and compared, resulting in the validation of the mathematical method for the assessment of internal contamination of American deposited in skeleton. (Author) 16 refs.

  18. Identification of two apolipoprotein variants, A-I Karatsu (Tyr 100-->His) and A-I Kurume (His 162-->Gln). (United States)

    Moriyama, K; Sasaki, J; Matsunaga, A; Takada, Y; Kagimoto, M; Arakawa, K


    We identified two apolipoprotein (apo) A-I variants, using isoelectric focusing gel electrophoresis: apo A-I Karatsu, which had a relative charge of +1 compared to normal apo A-I4, and apo A-I Kurume, which had a relative charge of -1. Direct sequence analysis of the PCR-amplified DNA from the proband of apo A-I Karatsu revealed a single substitution of tyrosine (TAC) for histidine (CAC) at position 100. Sequence analysis of apo A-I Kurume revealed a single substitution of histidine (CAT) for glutamine (CAG) at position 162. Probands of these two mutants and limited family study showed no accelerated atherosclerosis.

  19. Contributions to a Marxist Critical Pedagogy: Revisiting Marx&apos;s Humanism (United States)

    Malott, Curry


    In this essay Malott makes a case for a Marxist-informed critical pedagogy situating Marx&apos;s approach to Hegelian dialectics at the center. After reviewing Marx&apos;s critique of Hegel in his 1844 manuscripts, Malott outlines Marx&apos;s shifting conception of the falling rate of profit reflecting his developing understanding of what the…

  20. Contributions to a Marxist Critical Pedagogy: Revisiting Marx&apos;s Humanism (United States)

    Malott, Curry


    In this essay Malott makes a case for a Marxist-informed critical pedagogy situating Marx&apos;s approach to Hegelian dialectics at the center. After reviewing Marx&apos;s critique of Hegel in his 1844 manuscripts, Malott outlines Marx&apos;s shifting conception of the falling rate of profit reflecting his developing understanding of what the…

  1. The Security of Russia&apos;s Nuclear Arsenal: The Human Factor

    Energy Technology Data Exchange (ETDEWEB)

    Ball, D.Y.


    Assertions by the Russian military that all of their nuclear weapons are secure against theft and that nuclear units within the military are somehow insulated from the problems plaguing the Russian military should not be accepted uncritically. Accordingly, we should not give unwarranted credence to the pronouncements of military figures like Cal.-Gen. Igor Valynkin, Chief of the Defense Ministry&apos;s 12th Main Directorate, which oversees the country&apos;s nuclear arsenal. He contends that &apos;&apos;Russian nuclear weapons are under reliable supervision&apos;&apos; and that &apos;&apos;talk about the unreliability of our control over nuclear weapons has only one pragmatic goal--to convince international society that the country is incapable of maintaining nuclear safety and to introduce international oversight over those weapons, as it is done, for example, in Iraq.&apos;&apos; While the comparison to Iraq is preposterous, many analysts might agree with Valynkin&apos;s sanguine appraisal of the security of Russia&apos;s nuclear weapons. In contrast, I argue that the numerous difficulties confronting the military as a whole should cause concern in the West over the security of the Russian nuclear arsenal.

  2. Human ApoD, an apolipoprotein up-regulated in neurodegenerative diseases, extends lifespan and increases stress resistance in Drosophila. (United States)

    Muffat, Julien; Walker, David W; Benzer, Seymour


    Apolipoprotein D (ApoD) expression increases in several neurological disorders and in spinal cord injury. We provide a report of a physiological role for human ApoD (hApoD): Flies overexpressing hApoD are long-lived and protected against stress conditions associated with aging and neurodegeneration, including hyperoxia, dietary paraquat, and heat stress. We show that the fly ortholog, Glial Lazarillo, is strongly up-regulated in response to these extrinsic stresses and also can protect in vitro-cultured cells in situations modeling Alzheimer's disease (AD) and Parkinson's disease (PD). In adult flies, hApoD overexpression reduces age-associated lipid peroxide accumulation, suggesting a proximal mechanism of action. Similar data obtained in the mouse [Ganfornina, M.D., et al., (2008) Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress. Aging Cell 10.1111/j.1474-9726.2008.00395.] as well as in plants (Charron et al., personal communication) suggest that ApoD and its orthologs play an evolutionarily conserved role in response to stress, possibly managing or preventing lipid peroxidation.

  3. Acute effects of interleukin-6 infusion on apo-B-containing lipoprotein subclasses in humans

    DEFF Research Database (Denmark)

    Bagdade, John; Pedersen, Bente K; Schwenke, Dawn


    IL-6 is believed to mediate the elevation in plasma TG and VLDL lipids in patients with sepsis. Previous studies of lipoprotein density fractions do not reveal the extent to which cytokines change the immunochemically distinct TG-rich (LpB:C, LpB:C:E, LpAII:B:C:D:E) and cholesterol-rich (LpB, LpB...... the transport of apoB particles that contain apoE. Since apoE has immunomodulatory and host defense functions, these changes may be a previously unrecognized early step in the innate immune response....

  4. Implementing a Cross-District Principal Mentoring Program: A Human Resources Approach to Developing Midcareer Principals&apos; Leadership Capacities (United States)

    Della Sala, Matthew R.; Klar, Hans W.; Lindle, Jane Clark; Reese, Kenyae L.; Knoeppel, Robert C.; Campbell, Michael; Buskey, Frederick C.


    Despite the key role that principals play in leading schoolwide change, districts&apos; efforts to support principals are often limited, particularly in rural settings. In this article, we report the preliminary findings of a cross-district mentoring program for nine midcareer rural school principals. The collaboratively developed human resource…

  5. Inner ring deiodination of thyroxine and 3,5,3&apos;-triiodothyronine by human fetal membranes

    Energy Technology Data Exchange (ETDEWEB)

    Roti, E.; Fang, S.L.; Green, K.; Braverman, L.E.; Emerson, C.H.


    Indirect evidence, based on injection of thyroxine (T4) into the amniotic cavity of humans, and maternal thyroidectomy in the rat, suggests that fetal membranes might be capable of converting T4 to 3,3&apos;,5&apos;-triiodothyronine (rT3) by virtue of inner ring iodothyronine deiodinase activity. The present study was undertaken to provide direct evidence that human fetal membranes contain inner ring iodothyronine deiodinase activity directed toward T4 and 3,5,3&apos;-triiodothyronine (T3). Homogenates of human fetal membranes were incubated with 125I-labeled T4, rT3, and T3, and with stable T4. Conversion of 125(I)-T4 to 125(I)-rT3 was noted in chorion and amnion. 125I-T3 was converted to 125(I)-3,3&apos;-diiodothyronine (T2) in chorion and amnion. 125(I)-rT3 was stable in fetal membranes under the incubation conditions employed. Time-, temperature-, pH-, and protein content-dependent conversion of stable T4 to rT3 was found in fetal membranes. Iodothyronine metabolism did not occur in the absence of dithiothreitol. These studies indicate that human fetal membranes contain an inner ring deiodinase enzyme. Because of its intimate contact with the amniotic cavity, this enzyme may generate a portion of the rT3 found in amniotic fluid.

  6. Apolipoprotein modulation of streptococcal serum opacity factor activity against human plasma high-density lipoproteins. (United States)

    Rosales, Corina; Gillard, Baiba K; Courtney, Harry S; Blanco-Vaca, Francisco; Pownall, Henry J


    Human plasma HDL are the target of streptococcal serum opacity factor (SOF), a virulence factor that clouds human plasma. Recombinant (r) SOF transfers cholesteryl esters (CE) from approximately 400,000 HDL particles to a CE-rich microemulsion (CERM), forms a cholesterol-poor HDL-like particle (neo HDL), and releases lipid-free (LF) apo A-I. Whereas the rSOF reaction requires labile apo A-I, the modulation effects of other apos are not known. We compared the products and rates of the rSOF reaction against human HDL and HDL from mice overexpressing apos A-I and A-II. Kinetic studies showed that the reactivity of various HDL species is apo-specific. LpA-I reacts faster than LpA-I/A-II. Adding apos A-I and A-II inhibited the SOF reaction, an effect that was more profound for apo A-II. The rate of SOF-mediated CERM formation was slower against HDL from mice expressing human apos A-I and A-II than against WT mice HDL and slowest against HDL from apo A-II overexpressing mice. The lower reactivity of SOF against HDL containing human apos is due to the higher hydropathy of human apo A-I, particularly its C-terminus relative to mouse apo A-I, and the higher lipophilicity of human apo A-II. The SOF-catalyzed reaction is the first to target HDL rather than its transporters and receptors in a way that enhances reverse cholesterol transport (RCT). Thus, effects of apos on the SOF reaction are highly relevant. Our studies show that the "humanized" apo A-I-expressing mouse is a good animal model for studies of rSOF effects on RCT in vivo.

  7. HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging. (United States)

    Jazwinski, S Michal; Kim, Sangkyu; Dai, Jianliang; Li, Li; Bi, Xiuhua; Jiang, James C; Arnold, Jonathan; Batzer, Mark A; Walker, Jerilyn A; Welsh, David A; Lefante, Christina M; Volaufova, Julia; Myers, Leann; Su, L Joseph; Hausman, Dorothy B; Miceli, Michael V; Ravussin, Eric; Poon, Leonard W; Cherry, Katie E; Welsch, Michael A


    The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity.

  8. Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer's disease pathogenesis. (United States)

    Zhu, Li; Zhong, Minghao; Elder, Gregory A; Sano, Mary; Holtzman, David M; Gandy, Sam; Cardozo, Christopher; Haroutunian, Vahram; Robakis, Nikolaos K; Cai, Dongming


    The apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for developing sporadic Alzheimer's disease (AD). However, the mechanisms underlying the pathogenic nature of ApoE4 are not well understood. In this study, we have found that ApoE proteins are critical determinants of brain phospholipid homeostasis and that the ApoE4 isoform is dysfunctional in this process. We have found that the levels of phosphoinositol biphosphate (PIP2) are reduced in postmortem human brain tissues of ApoE4 carriers, in the brains of ApoE4 knock-in (KI) mice, and in primary neurons expressing ApoE4 alleles compared with those levels in ApoE3 counterparts. These changes are secondary to increased expression of a PIP2-degrading enzyme, the phosphoinositol phosphatase synaptojanin 1 (synj1), in ApoE4 carriers. Genetic reduction of synj1 in ApoE4 KI mouse models restores PIP2 levels and, more important, rescues AD-related cognitive deficits in these mice. Further studies indicate that ApoE4 behaves similar to ApoE null conditions, which fails to degrade synj1 mRNA efficiently, unlike ApoE3 does. These data suggest a loss of function of ApoE4 genotype. Together, our data uncover a previously unidentified mechanism that links ApoE4-induced phospholipid changes to the pathogenic nature of ApoE4 in AD.

  9. &apos;Wave-type&apos; structure of a synthetic hexaglycosylated decapeptide: A part of the extracellular domain of human glycophorin A

    Energy Technology Data Exchange (ETDEWEB)

    Schuster, Oliver; Klich, Gunther; Sinnwell, Volker; Kraenz, Helge; Paulsen, Hans; Meyer, Bernd [University of Hamburg, Institute for Organic Chemistry, Department of Chemistry (Germany)


    The three-dimensional structure of a glycopeptide, His-Thr*-Ser*-Thr*-Ser*-Ser*-Ser*-Val-Thr-Lys, with 2-acetamido-2-deoxy-{alpha}-D-galactose (GalNAc) residues linked to six adjacent amino acids from Thr-10 to Ser-15, was studied by NMR spectroscopy and molecular dynamics (MD) simulations. The hexaglycosylated decapeptide is part of the extracellular domain of human glycophorin A and shows an extended structure of the peptide backbone due to O-glycosylation. Furthermore, each GalNAc residue exhibits one and only one NOE contact from the NHAc proton to the backbone amide proton of the amino acid that the sugar is directly bound to. This indicates a strong preference for the orientation of all GalNAc residues towards the N-terminus. NOE build-up curves were used to determine 42 inter-proton distances that, in connection with {phi} angles of the peptide backbone obtained from 3J-coupling constants, resulted in constraints for a MD simulation in water. The NMR data and the MD simulations show a preference for an extended backbone structure. The GalNAc residues are located alternatingly on opposite sides of the backbone and reduce the flexibility of the peptide backbone. The conformation of the molecule is relatively rigid and shows a &apos;wave-type&apos; 3D structure of the peptide backbone within the glycosylation cluster. This new structural element is also supported by the unusual CD spectrum of the glycopeptide.

  10. Inhibitory effects of oleoylethanolamide (OEA) on H₂O₂-induced human umbilical vein endothelial cell (HUVEC) injury and apolipoprotein E knockout (ApoE-/-) atherosclerotic mice. (United States)

    Ma, Li; Guo, Xiaobing; Chen, Wei


    Atherosclerosis (AS) is initiated by vascular endothelial cell injury, which is induced by lipid and protein oxidation. Oleoylethanolamide (OEA), a dietary fat-derived lipid, has shown atheroprotective effect. In vitro studies demonstrated that OEA showed cytoprotective effects on H2O2-induced primary cultured human umbilical vein endothelial cell (HUVEC) injury model. Further investigation of the cytoprotective effects of OEA demonstrated that OEA exerted its function by scavenging for reactive oxygen species, as well as increasing anti-oxidative enzymes, reducing lipid peroxidation, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and apoptosis-related proteins expression. The in vivo study using an ApoE-/- mouse model fed with high-fat diet for 8 weeks showed that OEA (10 mg/kg/day, i.g.) administration reduced blood lipid levels, prevented endothelial cell damage and inhibited early AS plaque formation. In conclusion, our results suggested that OEA exerted a pharmacological effect on ameliorating atherosclerotic plaque formation through the inhibition of oxidative stress-induced endothelial cell injury and therefore OEA can be a potential candidate drug for anti-atherosclerosis.

  11. Oxidation of sitosterol and transport of its 7-oxygenated products from different tissues in humans and ApoE knockout mice. (United States)

    Schött, Hans-Frieder; Baumgartner, Sabine; Husche, Constanze; Luister, Alexandra; Friedrichs, Silvia; Miller, Charlotte M; McCarthy, Florence O; Plat, Jogchum; Laufs, Ulrich; Weingärtner, Oliver; Lütjohann, Dieter


    The most common phytosterols in the human diet are sitosterol and campesterol, which originate exclusively from plant derived food. These phytosterols are taken up by NPC1L1 transport from the intestine into the enterocytes together with cholesterol and other xenosterols. Phytosterols are selectively pumped back from the enterocytes into the intestinal lumen and on the liver site from hepatocytes into bile by heterodimeric ABCG5/G8 transporters. Like cholesterol, both phytosterols are prone to ring and side chain oxidation. It could be shown that oxyphytosterols, found in atherosclerotic tissue, are most likely of in situ oxidation (Schött et al.; Biochem. Biophys. Res. Commun. 2014 Apr 11;446(3):805-10). However, up to now, the entire mechanism of phytosterol oxidation is not clearly understood. Here, we provide further information about the oxidation of sitosterol and the transport of its oxidation products out of tissue. Our survey includes data of 104 severe aortic stenosis patients that underwent an elective aortic valve cusp replacement. We studied their phytosterol concentrations, as well as absolute and substrate corrected oxyphytosterol levels in plasma and valve cusp tissue. In addition, we also examined phytosterol and oxyphytosterol concentrations in plasma and tissues (from brain and liver) of 10 male ApoE knockout mice. The ratio of 7-oxygenated-sitosterol-to-sitosterol exceeds the ratio for 7-oxygenated-campesterol-to-campesterol in plasma and tissue of both humans and mice. This finding indicates that sitosterol is oxidized to a higher amount than campesterol and that a selective oxidative mechanism might exist which can differentiate between certain phytosterols. Secondly, the concentrations of oxyphytosterols found in plasma and tissue support the idea that oxysitosterols are preferably transported out of individual tissues. Selective oxidation of sitosterol and preferred transport of sitosterol oxidation products out of tissue seem to be a

  12. The structure of apo human glutamate dehydrogenase details subunit communication and allostery. (United States)

    Smith, Thomas J; Schmidt, Timothy; Fang, Jie; Wu, Jane; Siuzdak, Gary; Stanley, Charles A


    The structure of human glutamate dehydrogenase (GDH) has been determined in the absence of active site and regulatory ligands. Compared to the structures of bovine GDH that were complexed with coenzyme and substrate, the NAD binding domain is rotated away from the glutamate-binding domain. The electron density of this domain is more disordered the further it is from the pivot helix. Mass spectrometry results suggest that this is likely due to the apo form being more dynamic than the closed form. The antenna undergoes significant conformational changes as the catalytic cleft opens. The ascending helix in the antenna moves in a clockwise manner and the helix in the descending strand contracts in a manner akin to the relaxation of an extended spring. A number of spontaneous mutations in this antenna region cause the hyperinsulinism/hyperammonemia syndrome by decreasing GDH sensitivity to the inhibitor, GTP. Since these residues do not directly contact the bound GTP, the conformational changes in the antenna are apparently crucial to GTP inhibition. In the open conformation, the GTP binding site is distorted such that it can no longer bind GTP. In contrast, ADP binding benefits by the opening of the catalytic cleft since R463 on the pivot helix is pushed into contact distance with the beta-phosphate of ADP. These results support the previous proposal that purines regulate GDH activity by altering the dynamics of the NAD binding domain. Finally, a possible structural mechanism for negative cooperativity is presented.

  13. Strontium-90 content of human bone collected in 1967; Teneur en strontium 90 d&apos;os humains preleves en 1967

    Energy Technology Data Exchange (ETDEWEB)

    Jeanmaire, L.; Patti, F. [Commissariat a l' Energie Atomique, Fontenay-Aux-Roses (France). Centre d' Etudes Nucleaires


    This report follows report CEA-R-3381 and presents the strontium 90 content of human bones collected in 1967 in the Paris area. The main trend is much the same as during 1966; contamination levels are falling down in infants up to 5 year old. Beyond this age, the values are the same or experience a slight increase. (authors) [French] Ce rapport fait suite au rapport CEA-R-3381 et indique les teneurs en strontium 90 d&apos;os humains preleves au cours de l&apos;annee 1967 dans la region parisienne. L&apos;evolution generale des resultats est sensiblement la meme qu&apos;au cours de l&apos;annee 1966; nous assistons a une baisse de la contamination chez les enfants jusqu&apos;a 5 ans. Au-dela de cet ge, les valeurs sont les memes, ou en legere augmentation. (auteurs)

  14. X-spectrographic method for plutonium detection. Application to contamination measurements in humans; Etude d&apos;une methode de detection du plutonium par spectrographie X. Application a la mesure des contaminations sur l&apos;homme

    Energy Technology Data Exchange (ETDEWEB)

    Michel Trouble [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires


    After reviewing the radio-toxicology of plutonium 239 and conventional detection methods using its {alpha}-radiation, the author considers the measurement of the X emission spectrum of plutonium 239 using a proportional counter filled with argon under pressure. This preliminary work leads to the third part of this research involving the detailed study of the possibilities of applying thin alkali halide crystal scintillators to the detection of soft plutonium X-rays; there follows a systematic study of all the parameters liable to render the detection as sensitive as possible: movement due to the photomultiplier itself and its accessory electronic equipment, nature and size of the crystal scintillator as well as its mode of preparation, shielding against external parasitic radiation. Examples of some applications to the measurement of contamination in humans give an idea of the sensitivity of this method. (author) [French] Apres un apercu de la radiotoxicologie du plutonium 239 et des methodes classiques de detection par son rayonnement {alpha}, on etudie le spectre d&apos;emission X du plutonium 239 avec un compteur proportionnel rempli avec de l&apos;argon sous pression. Ce travail preliminaire permet d&apos;aborder la troisieme partie de cette etude dans laquelle nous examinons d&apos;une fagon approfondie les possibilites d&apos;application des cristaux scintillateurs minces d&apos;halogenure alcalin a la detection du rayonnement X mou du plutonium; suit une etude systematique de tous les parametres susceptibles de rendre la detection aussi sensible que possible: mouvement propre du photomultiplicateur et de l&apos;electronique associee, nature et dimensions du cristal scintillateur ainsi que son mode de fabrication, blindage contre les rayonnements parasites exterieurs. Quelques applications a la mesure des contaminations sur l&apos;homme permettent d&apos;apprecier la sensibilite de cette methode. (auteur)

  15. ApoB/ApoA-1 ratio and nitric oxide levels in pregnancy induced hypertensive women

    Directory of Open Access Journals (Sweden)

    Visala Sree Jammalamadaga


    Results: The SBP and DBP were significantly high between 3 groups. The mean plasma TC, TGL, VLDL, LDL, MDA, ApoB levels, ApoB/ApoA-I were significantly high and HDL, ApoA-I, NO, FRAP levels were significantly low between 3 groups. The ApoB/ApoA-I was positively correlated with TC, TGL, VLDL, LDL, malondialdehyde and negatively correlated with HDL, FRAP and NO. Conclusions: Our results indicate that women with PE and E exhibit markedly elevated concentrations of TGL-rich lipoproteins. The negative correlation between ApoB/ApoA-I with NO indicates that the hyperlipidemia is directly related with severity of ED in PIH. So, careful monitoring of ApoB/ApoA-I along with NO might be helpful to predict the onset and progression of the disease. [Int J Res Med Sci 2016; 4(5.000: 1329-1334

  16. Roles of apolipoprotein E4 (ApoE4) in the pathogenesis of Alzheimer's disease: lessons from ApoE mouse models. (United States)

    Huang, Yadong


    ApoE4 (apolipoprotein E4) is the major known genetic risk factor for AD (Alzheimer's disease). In most clinical studies, apoE4 carriers account for 65-80% of all AD cases, highlighting the importance of apoE4 in AD pathogenesis. Emerging data suggest that apoE4, with its multiple cellular origins and multiple structural and biophysical properties, contributes to AD in multiple ways either independently or in combination with other factors, such as Aβ (amyloid β-peptide) and tau. Many apoE mouse models have been established to study the mechanisms underlying the pathogenic actions of apoE4. These include transgenic mice expressing different apoE isoforms in neurons or astrocytes, those expressing neurotoxic apoE4 fragments in neurons and human apoE isoform knock-in mice. Since apoE is expressed in different types of cells, including astrocytes and neurons, and in brains under diverse physiological and/or pathophysiological conditions, these apoE mouse models provide unique tools to study the cellular source-dependent roles of apoE isoforms in neurobiology and in the pathogenesis of AD. They also provide useful tools for discovery and development of drugs targeting apoE4's detrimental effects.

  17. Human resources as multiplier for a company&apos;s value; Humankapital als Multiplikator fuer den Unternehmenswert

    Energy Technology Data Exchange (ETDEWEB)

    Bornemann, Manfred [Intangible Assets Consulting GmbH, Graz (Austria)


    On the basis of concrete examples this article demonstrates how knowledge of employees is integrated into value-added processes and how the status quo can be evaluated and developed in relation to strategic requirements. It will be shown why human resources are the strongest means concerning the implementation of measurements for a company&apos;s development and for the achievement of entrepreneurial objectives, and which challenges exist for the development of human resources in an increasingly skill-intensive performance routine. (orig.)

  18. The insecticide lindane. Identification of possible risks for human reproduction; L&apos;insetticida lindano. Identificazione dei rischi possibili per la riproduzione umana

    Energy Technology Data Exchange (ETDEWEB)

    Traina, M.E.; Urbani, E. [Istituto Superiore di Sanita' , Lab. di Igiene Ambientale, Rome (Italy); Rescia, M.; Mantovani, A. [Istituto Superiore di Sanita' , Lab. di Tossicologia Comparata e Ecotossicologia, Rome (Italy)


    A growing international concern exists about the potential harm to human reproduction caused by pollutants able to interfere with the endocrine system. Particular interest is addressed to organochlorine pesticides persisting in the environment and organisms; such compounds are extensively studied for their adverse effects on reproductive functions and development of laboratory animals. The insecticide lindane (the {gamma}-isomer of hexachlorocyclohexane), widely used before the 80s, has yet to be adequately evaluated as regards the possible reproductive risk. The present report contains a critical revision of the available scientific literature about lindane effects on the male and female reproductive system, pregnancy and development. Besides, the possible higher exposure periods to this pesticide (years 60s-70s) have been determined through the analysis of the lindane products consumed and the evaluation of the active ingredient levels in the environment and in the tissues and biological fluids, with particular regard to Italy. The present review aims at supporting further toxicological and epidemiological studies to assess the possible reproductive risk posed by environmental and professional exposure to chlorinated insecticides. [Italian] L&apos;ipotesi che l&apos;esposizione a sostanze inquinanti in grado di alterare l&apos;equilibrio del sistema endocrino possa avere effetti sulla riproduzione umana e sullo sviluppo e&apos; attualmente oggetto d&apos;interesse nella comunita&apos; scientifica. Particoalre attenzione e&apos; stata indirizzata ai pesticidi organoclorurati a lunga persistenza nell&apos;ambiente e negli organismi, per i quali esistono numerose evidenze di effetti nocivi per la riproduzione, negli studi di tossicologia sperimentale. L&apos;insetticida lindano (l&apos;isomero-{gamma} dell&apos;esaclorocicloesano), largamente utilizzato prima degli anni &apos;80, non e&apos; stato fino ad oggi adeguatamente valutato per un possibile rischio

  19. The new diagnosing method basing on the frequency analysis of human&apos;s nails in T-RAY

    Energy Technology Data Exchange (ETDEWEB)

    Ma Pengcheng; Xiao Long, E-mail: [Wuhan National Laboratory for Optoelectronics, College of Optoelectronic Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China)


    It has been reported that many kinds of sickness can be reflected in one&apos;s nails. And because of the special composition and structure of nails, they are very suitable for T-ray detecting. Therefore we want to see whether we can diagnose some sickness by only analyzing the transmission of the nails. The experiments consist of three parts. In the first part, we took 200 samples which came from about 20 years old people. By that way, we got that the peak transmission wavelengths of human&apos;s nail is about 1.7 THz and we almost acknowledged the characteristics of nails. Then we changed our samples coming from different ages, and some interesting phenomenon were coming out. Lastly, by detecting the nails which are taken from special patients, we discovered some sickness can be detected using T-ray.

  20. The Apolipoprotein B/Apolipoprotein A-I Ratio as a Potential Marker of Plasma Atherogenicity

    Directory of Open Access Journals (Sweden)

    Anastasiya M. Kaneva


    Full Text Available Background. The apolipoprotein (apo B/apoA-I ratio represents the balance between apoB-rich atherogenic particles and apoA-I-rich antiatherogenic particles, and this ratio is considered to be a marker of cardiovascular risk. Although many studies have demonstrated the importance of the apoB/apoA-I ratio in predicting the presence or absence of cardiovascular disease, less is known about apoB/apoA-I ratio as a marker of plasma atherogenicity. Methods. A total of 157 normolipidemic men aged 20–59 years were included in the study. The plasma levels of total cholesterol (TC, triglycerides (TG, high-density lipoprotein cholesterol (HDL-C, apoA-I, apoB, and apoE were determined after a 12 h fasting period. Results. The median of the apoB/apoA-I ratio in the studied normolipidemic subjects was 0.52, with values ranging from 0.19 to 2.60. The percentage of subjects with the apoB/apoA-I ratio exceeding 0.9 (the accepted risk value of cardiovascular disease was 19.1%. The subjects with apoB/apoA-I>0.9 were characterized by higher TG levels and atherogenic index of plasma (AIP and lower values of ratio of low-density lipoprotein cholesterol (LDL-C to apoB (LDL-C/apoB and apoE levels compared with men with apoB/apoA-I<0.9. Conclusion. Despite normolipidemia, the subjects with the unfavorable apoB/apoA-I ratio had more atherogenic lipid profile.

  1. As Luck Would Have It: Thomas Hardy&apos;s "Bildungsroman" on Leading a Human Life (United States)

    Laverty, Megan Jane


    In this essay, I demonstrate the value of the Bildungsroman for philosophy of education on the grounds that these narratives raise and explore educational questions. I focus on a short story in the Bildungsroman tradition, Thomas Hardy&apos;s "A Mere Interlude". This story describes the maturation of its heroine by narrating a series of…

  2. Science and the Humanities: Stephen Jay Gould&apos;s Quest to Join the High Table (United States)

    Ruse, Michael


    Stephen Jay Gould was a scientist, a paleobiologist, who was also a professional-level historian of science. This essay explores Gould&apos;s work, showing how he used the history of science to further his agenda as a working scientist.

  3. Science and the Humanities: Stephen Jay Gould&apos;s Quest to Join the High Table (United States)

    Ruse, Michael


    Stephen Jay Gould was a scientist, a paleobiologist, who was also a professional-level historian of science. This essay explores Gould&apos;s work, showing how he used the history of science to further his agenda as a working scientist.

  4. Imaging Alzheimer&apos;s disease-related protein aggregates in human cells using a selenium label

    Energy Technology Data Exchange (ETDEWEB)

    McGuire, E K; McComb, D W; Porter, A E [Department of Materials, Imperial College, Exhibition Rd, London SW7 2AZ (United Kingdom); Motskin, M [Department of Anatomy, University of Cambridge, Downing St, Cambridge CB2 3DY (United Kingdom); Knowles, T P J [Nanoscience Centre, University of Cambridge, JJ Thomson Ave, Cambridge, CB3 0FF (United Kingdom); Dobson, C M, E-mail: [Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge CB2 1EW (United Kingdom)


    The aberrant folding and subsequent aggregation of proteins and peptides is associated with a range of pathological conditions from the systemic amyloidoses to neurodegenerative diseases such as Alzheimer&apos;s and Parkinson&apos;s diseases. While this link is well established there is a lack of understanding of the exact role protein aggregates play in disease pathogenesis. Part of the reason for this is that it has proved extremely challenging to characterise the localisation and structure of amyloid fibrils within the cellular environment due to a lack of contrast between the carbon rich protein aggregates and the carbon rich cell. We report a novel method for visualising Alzheimer&apos;s disease-related amyloid fibrils inside human cells without the use of invasive or unreliable stains or tags. The naturally occurring sulfur atom in the amyloid-{beta} peptide is replaced with a selenium atom, a heavier element in the same group of the periodic table of elements. Using high angle annular dark field (HAADF) in a scanning transmission electron microscopy (STEM) the selenium-labelled aggregates can be identified within the cellular environment.

  5. Interaction of human decapping scavenger with 5&apos; mRNA cap analogues: structural requirements for catalytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Darzynkiewicz, Zbigniew M [Department of Biophysics, Institute of Experimental Physics, Warsaw University, 93 Zwirki and Wigury Street, 02-089 Warsaw (Poland); Bojarska, Elzbieta [Department of Biophysics, Institute of Experimental Physics, Warsaw University, 93 Zwirki and Wigury Street, 02-089 Warsaw (Poland); Kowalska, Joanna [Department of Biophysics, Institute of Experimental Physics, Warsaw University, 93 Zwirki and Wigury Street, 02-089 Warsaw (Poland); Lewdorowicz, Magdalena [Department of Biophysics, Institute of Experimental Physics, Warsaw University, 93 Zwirki and Wigury Street, 02-089 Warsaw (Poland); Jemielity, Jacek [Department of Biophysics, Institute of Experimental Physics, Warsaw University, 93 Zwirki and Wigury Street, 02-089 Warsaw (Poland); Kalek, Marcin [Department of Biophysics, Institute of Experimental Physics, Warsaw University, 93 Zwirki and Wigury Street, 02-089 Warsaw (Poland); Stepinski, Janusz [Department of Biophysics, Institute of Experimental Physics, Warsaw University, 93 Zwirki and Wigury Street, 02-089 Warsaw (Poland); Davis, Richard E [Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, 12801 East 17th Avenue, Aurora, CO 80045 (United States); Darzynkiewicz, Edward [Department of Biophysics, Institute of Experimental Physics, Warsaw University, 93 Zwirki and Wigury Street, 02-089 Warsaw (Poland)


    The cap structure is a specific feature of the 5&apos; end of mRNA which plays an important role in the post-transcriptional control in gene expression. A major step of gene regulation occurs at the level of mRNA turnover. Degradation of most eukaryotic mRNAs entails the removal of the cap structure in the various pathways. A human scavenger decapping enzyme (hDcpS) catalyses the cleavage of the residual cap structure m{sup 7}GpppN and/or short oligonucleotides after the 3&apos; to 5&apos; exosom mediated digestion. In this paper we report a fluorescence study of association process of hDcpS with m{sup 7}GMP, m{sup 7}GDP and selected dinucleotide cap analogues resistant to enzymatic hydrolysis. The calculated values of association constants (K{sub as}) and corresponding Gibbs free energies ({delta}G{sup 0}) depend on the type of substituents and their positions in the cap molecule, indicating which structural modifications are crucial for the catalysis.

  6. 脂多糖对肝细胞烟酸受体表达及胆固醇外流的影响%Upregulation of niacin receptor GPR109A and reduction of cholesterol efflux to apoA-I in hepatocytes response to LPS treatment

    Institute of Scientific and Technical Information of China (English)

    李晓宇; 杨清; 单清


    in hepatocytes was low, we found that its expression was markedly unregulated in liver after injection of low- dose endotoxin. Furthermore, we found that this was due to upregulation in hepatocytes and not simple Kupffer cells. Then we confirmed the similar up-regulatory effect response to inflammation in human hepatocyte cell line. After using HepG2 cells treated with low dose LPS to compare with the control, we confirmed that forskolin- stimulated intracellular cAMP was significantly reduced in LPS treated HepG2 cells. Finally, we demonstrated that LPS treatment reduced ABCA1 mediated free cholesterol efflux to apoA- I from HepG2 cells. Conclusion These data suggest that increased GPR109A expression in hepatocytes response to LPS treatment may lead to reduced hepatocyte ABCA1 activity, decreased cholesterol efflux to nascent apoA~ I, and reduced levels of HDL- C. Though speculative, the results suggest that proinflam-matory states, such as those associated with obesity and insulin resistance, may be associated with upregulated hepatic expression of GPR109A.

  7. The &apos;'neural'&apos; phonetic typewriter

    Energy Technology Data Exchange (ETDEWEB)

    Kohonen, T.


    Recently, researchers have placed great hopes on artificial neural networks to perform such &apos;'natural'&apos; tasks as speech recognition. This was indeed one motivation for us to start research in this area many years ago at Helsinki University of Technology. This article describes the result of that research - a complete &apos;'neural'&apos; speech recognition system, which recognizes phonetic units, called phonemes, from a continuous speech signal. Although motivated by neural network principles, the choices in design must be regarded as a compromise of many technical aspects of those principles. As our system is a genuine &apos;&apos;phonetic typewriter&apos;&apos; intended to transcribe orthographically edited text from an unlimited vocabulary, it cannot be directed compared with any more conventional, word-based system that applies classical concepts such as dynamic time warping and hidden Markov models.

  8. C/EBP-β Is Differentially Affected by PPARα Agonists Fenofibric Acid and GW7647, But Does Not Change Apolipoprotein A-I Production During ER-Stress and Inflammation. (United States)

    van der Krieken, Sophie E; Popeijus, Herman E; Konings, Maurice; Dullens, Stefan P J; Mensink, Ronald P; Plat, Jogchum


    Increasing apolipoproteinA-I (apoA-I) production may be anti-atherogenic. Thus, there is a need to identify regulatory factors involved. Transcription of apoA-I involves peroxisome-proliferator-activated-receptor-alpha (PPARα) activation, but endoplasmic reticulum (ER) -stress and inflammation also influence apoA-I production. To unravel why PPARα agonist GW7647 increased apoA-I production compared to PPARα agonist fenofibric acid (FeAc) in human hepatocellular carcinoma (HepG2) and colorectal adenocarcinoma (CaCo-2) cells, gene expression profiles were compared. Microarray analyses suggested CCAAT/enhancer-binding-protein-beta (C/EBP-β) involvement in the FeAc condition. Therefore, C/EBP-β silencing and isoform-specific overexpression experiments were performed under ER-stressed, inflammatory and non-inflammatory conditions. mRNA expression of C/EBP-β, ATF3, NF-IL3 and GDF15 were upregulated by FeAc compared to GW7647 in both cell lines, while DDIT3 and DDIT4 mRNA were only upregulated in HepG2 cells. This ER-stress related signature was associated with decreased apoA-I secretion. After ER-stress induction by thapsigargin or FeAc addition, intracellular apoA-I concentrations decreased, while ER-stress marker expression (CHOP, XBP1s, C/EBP-β) increased. Cytokine addition increased intracellular C/EBP-β levels and lowered apoA-I concentrations. Although a C/EBP binding place is present in the apoA-I promoter, C/EBP-β silencing or isoform-specific overexpression did not affect apoA-I production in inflammatory, non-inflammatory and ER-stressed conditions. Therefore, C/EBP-β is not a target to influence hepatic apoA-I production. J. Cell. Biochem. 118: 754-763, 2017. © 2016 Wiley Periodicals, Inc.

  9. &apos;et&apos; special: &apos;&apos;E-world of energy&apos;&apos;; &apos;et&apos;-special: &apos;&apos;E-world of energy&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)



    The &apos;et&apos; special on the conference &apos;E-world of energy&apos;, held from February 13 - 15, 2001 in Essen (Germany) presents contributions of experts who offer solutions to issues and many topical questions arising in the business of traders and utilities as participants of (international) energy markets at various stages of transition towards workable competition. The translated titles of the 15 contributions reproduced in this &apos;et&apos; special indicate the major contents of the conference papers: 1. Internet-based wholesale power trading as a competitive option to the power exchange. 2. Forward graphs in European electricity markets. 3. Portfolio management in energy trading. 4. Risk management concepts in energy trading. 5. E-commerce as a driving force of a change in the energy markets. 6. eHuman resources management - a vital aspect of corporate success. 7. A brand policy for electricity? 8. Is it really only the price that counts for the customers? 9. The City Power network: an example of successful customer loyalty strategy for local and regional utilities. 10. The Call Center, an important instrument for customer loyalty programmes. 11. eCommerce or eLlusion? 12. eBusiness as a corporate strategy. 13. Meeting the challenges of increasing IT requirements. 14. IT solutions for transmission and distribution network management. 15. Target costing - pinpointed cost planning and control for the energy supply industry. (orig./CB) [German] In dem &apos;et&apos;-Special zur Konferenz &apos;E-world of energy&apos;, die vom 13.- 15. Februar 2001 in Essen stattfand, bieten Experten Loesungsvorschlaege fuer die aktuellen Fragen und Probleme an, die sich auf dem Weg zu liberalisierten Energiemaerkten stellen. Die folgenden Titel der 15 Beitraege geben eine Uebersicht ueber den Inhalt der Konferenzbeitraege. Themen: 1. Internetbasierte Grosshandelsmaerkte als Konkurrenz zu Energieboersen 2. Forward-Kurven in europaeischen Strommaerkten 3

  10. The Effect of a High-Fat Diet on Brain Plasticity, Inflammation and Cognition in Female ApoE4-Knockin and ApoE-Knockout Mice.

    Directory of Open Access Journals (Sweden)

    Carola I F Janssen

    Full Text Available Apolipoprotein E4 (ApoE4, one of three common isoforms of ApoE, is a major risk factor for late-onset Alzheimer disease (AD. ApoE-deficient mice, as well as mice expressing human ApoE4, display impaired learning and memory functions and signs of neurodegeneration. Moreover, ApoE protects against high-fat (HF diet induced neurodegeneration by its role in the maintenance of the integrity of the blood-brain barrier. The influence of a HF diet on the progression of AD-like cognitive and neuropathological changes was assessed in wild-type (WT, human ApoE4 and ApoE-knockout (ApoE-/- mice to evaluate the modulatory role of ApoE in this process. From 12 months of age, female WT, ApoE4, and ApoE-/- mice were fed either a standard or a HF diet (19% butter, 0.5% cholate, 1.25% cholesterol throughout life. At 15 months of age mice performed the Morris water maze, evaluating spatial learning and memory. ApoE-/- showed increased spatial learning compared to WT mice (p = 0.009. HF diet improved spatial learning in WT mice (p = 0.045, but did not affect ApoE4 and ApoE-/- mice. Immunohistochemical analyses of the hippocampus demonstrated increased neuroinflammation (CD68 in the cornu ammonis 1 (CA1 region in ApoE4 (p = 0.001 and in ApoE-/- (p = 0.032 mice on standard diet. HF diet tended to increase CD68 in the CA1 in WT mice (p = 0.052, while it decreased in ApoE4 (p = 0.009, but ApoE-/- remained unaffected. A trend towards increased neurogenesis (DCX was found in both ApoE4 (p = 0.052 and ApoE-/- mice (p = 0.068. In conclusion, these data suggest that HF intake induces different effects in WT mice compared to ApoE4 and ApoE-/- with respect to markers for cognition and neurodegeneration. We propose that HF intake inhibits the compensatory mechanisms of neuroinflammation and neurogenesis in aged female ApoE4 and ApoE-/- mice.

  11. Isolation and characterization of the human tyrosine hydroxylase gene: identification of 5&apos; alternative splice sites responsible for multiple mRNAs

    Energy Technology Data Exchange (ETDEWEB)

    O' Malley, K.L.; Anhalt, M.J.; Martin, B.M.; Kelsoe, J.R.; Winfield, S.L.; Ginns, E.I.


    A full-length genomic clone for human tyrosine hydroxylase (L-tyrosine, tetrahydropteridine:oxygen oxidoreductase, EC has been isolated. A human brain genomic library constructed in EMBL3 was screened by using a rat cDNA for tyrosine hydroxylase as a probe. Out of one million recombinant phage, one clone was identified that hybridized to both 5&apos; and 3&apos; rat cDNA probes. Restriction endonuclease mapping, Southern blotting, and sequence analysis revealed that, like its rodent counterpart, the human gene is single copy, contains 13 primary exons, and spans approximately 8 kilobases (kb). In contrast to the rat gene, human tyrosine hydroxylase undergoes alternative RNA processing within intron 1, generating at least three distinct mRNAs. A comparison of the human tyrosine hydroxylase and phenylalanine hydroxylase genes indicates that although both probably evolved from a common ancestral gene, major changes in the size of introns have occurred since their divergence.

  12. Apolipoprotein A-I and A-I mimetic peptides: a role in atherosclerosis

    Directory of Open Access Journals (Sweden)

    Getz GS


    Full Text Available Godfrey S Getz, Catherine A ReardonThe University of Chicago, Department of Pathology, Chicago, IL, USAAbstract: Cardiovascular disease remains a major cause of morbidity and mortality in the westernized world. Atherosclerosis is the underlying cause of most cardiovascular diseases. Atherosclerosis is a slowly evolving chronic inflammatory disorder involving the intima of large and medium sized arteries that is initiated in response to high plasma lipid levels, especially LDL. Cells of both the innate and adaptive immunity are involved in this chronic inflammation. Although high plasma LDL levels are a major contributor to most stages of the evolution of atherosclerosis, HDL and its major protein apoA-I possess properties that attenuate and may even reverse atherosclerosis. Two major functions are the ability to induce the efflux of cholesterol from cells, particularly lipid-loaded macrophages, in the artery wall for transfer to the liver, a process referred to as reverse cholesterol transport, and the ability to attenuate the pro-inflammatory properties of LDL. The removal of cellular cholesterol from lipid-loaded macrophages may also be anti-inflammatory. One of the most promising therapies to enhance the anti-atherogenic, anti-inflammatory properties of HDL is apoA-I mimetic peptides. Several of these peptides have been shown to promote cellular cholesterol efflux, attenuate the production of pro-inflammatory cytokines by macrophages, and to attenuate the pro-inflammatory properties of LDL. This latter effect may be related to their high affinity for oxidized lipids present in LDL. This review discusses the functional properties of the peptides and their effect on experimental atherosclerosis and the results of initial clinical studies in humans.Keywords: apoA-I, mimetic peptides, HDL, anti-inflammatory, atherosclerosis

  13. New views of dioxin&apos;s effect on human health

    Energy Technology Data Exchange (ETDEWEB)


    This paper reports that although dioxin has been shown to cause disease in animals, data from human studies collected over the last 30 years have failed to demonstrate a cause-and-effect relationship between exposure to dioxin and a variety of diseases, including cancer. This disparity leads many scientists and public health officials to question the value of using animal study data to assess human risk from dioxin exposure. And, as information from human studies has evolved, the scientific evidence strongly suggests that dioxin-at very low levels- does not constitute a significant health risk to humans.

  14. A novel BET bromodomain inhibitor, RVX-208, shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice. (United States)

    Jahagirdar, Ravi; Zhang, Haiyan; Azhar, Salman; Tobin, Jennifer; Attwell, Sarah; Yu, Raymond; Wu, Jin; McLure, Kevin G; Hansen, Henrik C; Wagner, Gregory S; Young, Peter R; Srivastava, Rai Ajit K; Wong, Norman C W; Johansson, Jan


    Despite the benefit of statins in reducing cardiovascular risk, a sizable proportion of patients still remain at risk. Since HDL reduces CVD risk through a process that involves formation of pre-beta particles that facilitates the removal of cholesterol from the lipid-laden macrophages in the arteries, inducing pre-beta particles, may reduce the risk of CVD. A novel BET bromodomain antagonist, RVX-208, was reported to raise apoA-I and increase preβ-HDL particles in non-human primates and humans. In the present study, we investigated the effect of RVX-208 on aortic lesion formation in hyperlipidemic apoE(-/-) mice. Oral treatments of apoE(-/-) mice with 150 mg/kg b.i.d RVX-208 for 12 weeks significantly reduced aortic lesion formation, accompanied by 2-fold increases in the levels of circulating HDL-C, and ∼50% decreases in LDL-C, although no significant changes in plasma apoA-I were observed. Circulating adhesion molecules as well as cytokines also showed significant reduction. Haptoglobin, a proinflammatory protein, known to bind with HDL/apoA-I, decreased >2.5-fold in the RVX-208 treated group. With a therapeutic dosing regimen in which mice were fed Western diet for 10 weeks to develop lesions followed by switching to a low fat diet and concurrent treatment with RVX-208 for 14 weeks, RVX-208 similarly reduced lesion formation by 39% in the whole aorta without significant changes in the plasma lipid parameters. RVX-208 significantly reduced the proinflammatory cytokines IP-10, MIP1(®) and MDC. These results show that the antiatherogenic activity of BET inhibitor, RVX-208, occurs via a combination of lipid changes and anti-inflammatory activities.

  15. &apos;'Order-order'&apos; relaxations in intermetallics

    Energy Technology Data Exchange (ETDEWEB)

    Kozubski, R.; Kozlowski, M. [Jagellonian Univ., Krakow (Poland). M. Smoluchowski Inst. of Physics; Pierron-Bohnes, V. [Inst. de Physique et Chimie des Materiaux de Strasbourg, Strasbourg (France); Pfeiler, W. [Univ. Wien, Wien (Austria). Inst. fuer Materialphysik


    &apos;'Order-order'&apos; relaxation processes in high-temperature intermetallics occur after an abrupt change of temperature and are controlled by atomic migration in the almost perfect superstructure. The related experiments were carried out using systems being of technological interest and representing three common types of superstructures: L1{sub 2} (Ni{sub 3}Al-based quasi-binaries), L1{sub 0} (FePd, FePt) and B2 (NiAl, FeAl). The corresponding Monte Carlo (MC) simulations of &apos;'order-order'&apos; kinetics involving the Glauber dynamics implemented with vacancy mechanism for atomic jumps were performed. The studies indicate a crucial role of anti-site-easy-diffusion channels offered by particular superstructures in determining the character of &apos;'order-order'&apos; processes and their relationship to steady-state self-diffusion. Specific mechanisms of the relaxations in triple-defect B2-ordered binaries are discussed. (orig.)

  16. School Nurses&apos; Knowledge, Attitudes, Perceptions of Role as Opinion Leader, and Professional Practice Regarding Human Papillomavirus Vaccine for Youth (United States)

    Rosen, Brittany L.; Goodson, Patricia; Thompson, Bruce; Wilson, Kelly L.


    Background: Because human papillomavirus (HPV) vaccine rates remain low, we evaluated US school nurses&apos; knowledge, attitudes, perceptions of their role as opinion leaders, and professional practice regarding HPV vaccine, and assessed whether knowledge, attitudes, and perceptions of being an opinion leader influenced their professional…

  17. Situated Meaning-Making of the Human Body: A Study of Elementary School Children&apos;s Reasons in Two Different Activities (United States)

    Lundin, Mattias; Jakobson, Britt


    In this text we compare children&apos;s expressions in drawings to their statements during interviews, for the purpose of understanding how different situations afford children to make meaning. In specific we study how two different activities interact and afford children to make meaning differently about the human body. The analytic attention is…

  18. At the Very Root of the Development of Interest: Using Human Body Contexts to Improve Women&apos;s Emotional Engagement in Introductory Physics (United States)

    Allaire-Duquette, Geneviève; Charland, Patrick; Riopel, Martin


    In physics, women find contexts concerning human biology, medical applications, or natural phenomena highly relevant (Hoffmann, 2002), and the rareness or absence of these in physics curricula may make it more difficult for women to develop and maintain their interest in physics. To date, research in physics education addressing student&apos;s…

  19. Situated Meaning-Making of the Human Body: A Study of Elementary School Children&apos;s Reasons in Two Different Activities (United States)

    Lundin, Mattias; Jakobson, Britt


    In this text we compare children&apos;s expressions in drawings to their statements during interviews, for the purpose of understanding how different situations afford children to make meaning. In specific we study how two different activities interact and afford children to make meaning differently about the human body. The analytic attention is…

  20. The Future of the Humanities in Today&apos;s Financial Markets (United States)

    Lea, David


    In this essay David Lea approaches the decline in the study and teaching of the humanities within the university context from a financial perspective. As humanities departments are either closed down or have their curriculum attenuated, it is obvious that the revenue previously available to support such programs has not been forthcoming. This…

  1. An Anti-apoE4 Specific Monoclonal Antibody Counteracts the Pathological Effects of apoE4 In Vivo. (United States)

    Luz, Ishai; Liraz, Ori; Michaelson, Daniel M


    ApolipoproteinE4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD) and as such is a promising therapeutic target. This study examined the extent to which the pathological effects of apoE4 can be counteracted in vivo utilizing an immunological approach in which anti-apoE4 antibodies are applied peripherally by i.p. injections into apoE4-targeted replacement mice. Prerequisites for the successful pursuit of this objective are the availability of antibodies that specifically bind brain apoE4 and not apoE3, and demonstrating that direct application of these antibodies into the brain can counteract the effects of apoE4. Accordingly, it was shown that the antiapoE4 monoclonal antibody (mAb) 9D11 binds specifically to brain apoE4 and not apoE3. Direct i.c.v. application of mAb 9D11 prevented the apoE4-driven accumulation of Aβ in hippocampal neurons following activation of the amyloid cascade by inhibiting the Aβ-degrading enzyme neprilysin. These findings provide a proof-of-concept that anti-apoE4 mAb 9D11, when introduced into the brain, can counteract the apoE4 effects in vivo. Subsequent experiments, utilizing repeated i.p. injections of mAb 9D11, resulted in the formation of apoE/IgG complexes specifically in apoE4 mice. This was associated with reversal of the cognitive impairments of apoE4 in the Morris water maze and the novel object recognition test as well as with reversal of key apoE4-driven pathologies including the hyperphosphorylated tau and the reduced levels of the apoER2 receptor. These results indicate that anti-apoE4 immunotherapy counteracts the cognitive and brain pathological effects of apoE4, and suggest that such an approach could also benefit human apoE4 carriers.

  2. Overexpression of apolipoprotein O does not impact on plasma HDL levels or functionality in human apolipoprotein A-I transgenic mice

    NARCIS (Netherlands)

    Nijstad, Niels; de Boer, Jan Freark; Lagor, William R.; Toelle, Markus; Usher, David; Annema, Wijtske; van der Giet, Markus; Rader, Daniel J.; Tietge, Uwe J. F.

    Apolipoprotein (apo) O is a newly discovered apolipoprotein preferentially contained within HDL; however, currently, no data are available on the (patho)physiological effects of apoO. Therefore, the present study assessed the impact of apoO overexpression on (i) plasma lipids and lipoproteins as

  3. Anti-CD20 single chain variable antibody fragment-apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas. (United States)

    Crosby, Natasha M; Ghosh, Mistuni; Su, Betty; Beckstead, Jennifer A; Kamei, Ayako; Simonsen, Jens B; Luo, Bing; Gordon, Leo I; Forte, Trudy M; Ryan, Robert O


    A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents.

  4. Myeloperoxidase-mediated Methionine Oxidation Promotes an Amyloidogenic Outcome for Apolipoprotein A-I. (United States)

    Chan, Gary K L; Witkowski, Andrzej; Gantz, Donald L; Zhang, Tianqi O; Zanni, Martin T; Jayaraman, Shobini; Cavigiolio, Giorgio


    High plasma levels of apolipoprotein A-I (apoA-I) correlate with cardiovascular health, whereas dysfunctional apoA-I is a cause of atherosclerosis. In the atherosclerotic plaques, amyloid deposition increases with aging. Notably, apoA-I is the main component of these amyloids. Recent studies identified high levels of oxidized lipid-free apoA-I in atherosclerotic plaques. Likely, myeloperoxidase (MPO) secreted by activated macrophages in atherosclerotic lesions is the promoter of such apoA-I oxidation. We hypothesized that apoA-I oxidation by MPO levels similar to those present in the artery walls in atherosclerosis can promote apoA-I structural changes and amyloid fibril formation. ApoA-I was exposed to exhaustive chemical (H2O2) oxidation or physiological levels of enzymatic (MPO) oxidation and incubated at 37 °C and pH 6.0 to induce fibril formation. Both chemically and enzymatically oxidized apoA-I produced fibrillar amyloids after a few hours of incubation. The amyloid fibrils were composed of full-length apoA-I with differential oxidation of the three methionines. Met to Leu apoA-I variants were used to establish the predominant role of oxidation of Met-86 and Met-148 in the fibril formation process. Importantly, a small amount of preformed apoA-I fibrils was able to seed amyloid formation in oxidized apoA-I at pH 7.0. In contrast to hereditary amyloidosis, wherein specific mutations of apoA-I cause protein destabilization and amyloid deposition, oxidative conditions similar to those promoted by local inflammation in atherosclerosis are sufficient to transform full-length wild-type apoA-I into an amyloidogenic protein. Thus, MPO-mediated oxidation may be implicated in the mechanism that leads to amyloid deposition in the atherosclerotic plaques in vivo.

  5. Human Events Reference for ATHEANA (HERA) Database Description and Preliminary User&apos;s Manual

    Energy Technology Data Exchange (ETDEWEB)

    Auflick, J.L.


    The Technique for Human Error Analysis (ATHEANA) is a newly developed human reliability analysis (HRA) methodology that aims to facilitate better representation and integration of human performance into probabilistic risk assessment (PRA) modeling and quantification by analyzing risk-significant operating experience in the context of existing behavioral science models. The fundamental premise of ATHEANA is that error forcing contexts (EFCs), which refer to combinations of equipment/material conditions and performance shaping factors (PSFs), set up or create the conditions under which unsafe actions (UAs) can occur. Because ATHEANA relies heavily on the analysis of operational events that have already occurred as a mechanism for generating creative thinking about possible EFCs, a database (db) of analytical operational events, called the Human Events Reference for ATHEANA (HERA), has been developed to support the methodology. This report documents the initial development efforts for HERA.

  6. Postprandial apoE isoform and conformational changes associated with VLDL lipolysis products modulate monocyte inflammation.

    Directory of Open Access Journals (Sweden)

    Laura J den Hartigh

    Full Text Available Postprandial hyperlipemia, characterized by increased circulating very low-density lipoproteins (VLDL and circulating lipopolysaccharide (LPS, has been proposed as a mechanism of vascular injury. Our goal was to examine the interactions between postprandial lipoproteins, LPS, and apoE3 and apoE4 on monocyte activation.We showed that apoE3 complexed to phospholipid vesicles attenuates LPS-induced THP-1 monocyte cytokine expression, while apoE4 increases expression. ELISA revealed that apoE3 binds to LPS with higher affinity than apoE4. Electron paramagnetic resonance (EPR spectroscopy of site-directed spin labels placed on specific amino acids of apoE3 showed that LPS interferes with conformational changes normally associated with lipid binding. Specifically, compared to apoE4, apoE bearing the E3-like R112→Ser mutation displays increased self association when exposed to LPS, consistent with a stronger apoE3-LPS interaction. Additionally, lipolysis of fasting VLDL from normal human donors attenuated LPS-induced TNFα secretion from monocytes to a greater extent than postprandial VLDL, an effect partially reversed by blocking apoE. This effect was reproduced using fasting VLDL lipolysis products from e3/e3 donors, but not from e4/e4 subjects, suggesting that apoE3 on fasting VLDL prevents LPS-induced inflammation more readily than apoE4.Postprandial apoE isoform and conformational changes associated with VLDL dramatically modulate vascular inflammation.

  7. Strontium-90 content of human bones collected from 1962 to 1966; Teneur en strontium 90 d&apos;os humains preleves de 1962 a 1966

    Energy Technology Data Exchange (ETDEWEB)

    Jeanmaire, L. [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires


    The aim of this report is essentially to present results of {sup 90}Sr determination made on human bones collected in the Paris region from 1962 to 1966. The results are classified according to the year and the age-group in, two tables and one figure which show the general evolution of the contamination during this period. (author) [French] Le but de ce rapport est essentiellement de presenter les resultats des dosages de {sup 90}Sr effectues sur les os humains, preleves de 1962 a 1966 dans la region parisienne. L&apos;ensemble des resultats a ete groupe par annee et par tranche d&apos;age en deux tableaux et une figure, qui montrent l&apos;evolution generale de la contamination au cours de cette periode. (auteur)

  8. Humanity faced with climatic change; L&apos;Humanite face au changement climatique

    Energy Technology Data Exchange (ETDEWEB)

    Dautray, R.; Lesourne, J


    Humanity is for the first time confronted with a global change phenomenon of the eco-sphere which makes her entering a long transition era with at the same time economical, social and political impacts. Every country and every human activity will be impacted. The resulting problems may be solved by changing our way of life, limiting transports and by the large-scale implementation of existing technologies or technologies under development. The challenge is not to reject technology but to intensify the efforts to develop and adapt it according to the real needs of populations. (J.S.)

  9. Apolipoprotein E – Low Density Lipoprotein Receptor Interaction Affects Spatial Memory Retention and Brain ApoE Levels in an Isoform-Dependent Manner (United States)

    Johnson, Lance A.; Olsen, Reid H.J.; Merkens, Louise S.; DeBarber, Andrea; Steiner, Robert D.; Sullivan, Patrick M.; Maeda, Nobuyo; Raber, Jacob


    Human apolipoprotein E (apoE) exists in three isoforms: apoE2, apoE3 and apoE4. APOE ε4 (E4) is a major genetic risk factor for cardiovascular disease (CVD) and Alzheimer's disease (AD). ApoE mediates cholesterol metabolism by binding various receptors. The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>>E2). Evidence suggests that a functional interaction between apoE and LDLR influences the risk of CVD and AD. We hypothesize that the differential cognitive effects of the apoE isoforms are a direct result of their varying interactions with LDLR. To test this hypothesis, we have employed transgenic mice that express human apoE2, apoE3, or apoE4, and either human LDLR (hLDLR) or no LDLR (LDLR−/−). Our results show that plasma and brain apoE levels, cortical cholesterol, and spatial memory are all regulated by isoform-dependent interactions between apoE and LDLR. Conversely, both anxiety-like behavior and cued associative memory are strongly influenced by APOE genotype, but these processes appear to occur via an LDLR-independent mechanism. Both the lack of LDLR and the interaction between E4 and the LDLR were associated with significant impairments in the retention of long term spatial memory. Finally, levels of hippocampal apoE correlate with long term spatial memory retention in mice with human LDLR. In summary, we demonstrate that the apoE-LDLR interaction affects regional brain apoE levels, brain cholesterol, and cognitive function in an apoE isoform-dependent manner. PMID:24412220

  10. Apolipoprotein E-low density lipoprotein receptor interaction affects spatial memory retention and brain ApoE levels in an isoform-dependent manner. (United States)

    Johnson, Lance A; Olsen, Reid H J; Merkens, Louise S; DeBarber, Andrea; Steiner, Robert D; Sullivan, Patrick M; Maeda, Nobuyo; Raber, Jacob


    Human apolipoprotein E (apoE) exists in three isoforms: apoE2, apoE3 and apoE4. APOE ε4 is a major genetic risk factor for cardiovascular disease (CVD) and Alzheimer's disease (AD). ApoE mediates cholesterol metabolism by binding various receptors. The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>E2). Evidence suggests that a functional interaction between apoE and LDLR influences the risk of CVD and AD. We hypothesize that the differential cognitive effects of the apoE isoforms are a direct result of their varying interactions with LDLR. To test this hypothesis, we have employed transgenic mice that express human apoE2, apoE3, or apoE4, and either human LDLR (hLDLR) or no LDLR (LDLR(-/-)). Our results show that plasma and brain apoE levels, cortical cholesterol, and spatial memory are all regulated by isoform-dependent interactions between apoE and LDLR. Conversely, both anxiety-like behavior and cued associative memory are strongly influenced by APOE genotype, but these processes appear to occur via an LDLR-independent mechanism. Both the lack of LDLR and the interaction between E4 and the LDLR were associated with significant impairments in the retention of long term spatial memory. Finally, levels of hippocampal apoE correlate with long term spatial memory retention in mice with human LDLR. In summary, we demonstrate that the apoE-LDLR interaction affects regional brain apoE levels, brain cholesterol, and cognitive function in an apoE isoform-dependent manner. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Solar Energy Education. Humanities: activities and teacher&apos;s guide. Field test edition

    Energy Technology Data Exchange (ETDEWEB)


    Activities are outlined to introduce students to information on solar energy while performing ordinary classroom work. In this teaching manual solar energy is integrated with the humanities. The activities include such things as stories, newspapers, writing assignments, and art and musical presentations all filled with energy related terms. An energy glossary is provided. (BCS)

  12. Selective modulation of protein kinase isozymes by the site-selective analog 8-chloroadenosine 3&apos;,5&apos;-cyclic monophosphate provides a biological means for control of human colon cancer cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Ally, S.; Tortora, G.; Clair, T.; Grieco, D.; Merlo, G.; Katsaros, D.; Ogreid, D.; Doeskeland, S.O.; Jahnsen, T.; Cho-Chung, Yoonsang


    Differential expression of type I and type II cAMP-dependent protein kinase isozymes has been linked to growth regulation and differentiation. The authors examined the expression of protein kinase isozymes in the LS 174T human colon cancer cell line during 8-chloroadenosine 3&apos;,5&apos;-cyclic monophosphate (8-Cl-cAMP)-induced growth inhibition. Two species of R/sup II/ (the regulatory subunit of protein kinase type II) with apparent M/sub r/ 52,000 (R/sup II//sub 52/) and M/sub r/ 56,000 (R/sup II//sub 56/) and a single species of R/sup I/ (the regulatory subunit of protein kinase type I) with M/sub r/ 48,000 were identified in the cancer cells. R/sup I/ and both forms of R/sup II/ were covalently labeled with 8-azidoadenosine 3&apos;,5&apos;-cyclic (/sup 32/P)monophosphate, and two anti-R/sup II/ antibodies that exclusively recognize either R/sup II//sub 52/ or R/sup II//sub 56/ resolved two forms of the R/sup II/ receptors. 8-Cl-cAMP caused transcriptional activation of the R/sup II//sub 52/ receptor gene and inactivation of the R/sup I/ receptor gene. Thus, differential regulation of various forms of cAMP receptor proteins is involved in 8-Cl-cAMP-induced regulation of cancer cell growth, and nuclear translocation of R/sup II//sub 52/ receptor protein appears to be an early event in such differential regulation.

  13. The strategic &apos;'pull'&apos; and operational &apos;'push'&apos; of total quality management in UK regional electricity service companies

    Energy Technology Data Exchange (ETDEWEB)

    McAdam, R.; McLean, J.; Henderson, J.


    The aim of this paper is to evaluate whether the UK regional electricity companies (RECs) has used total quality management (TQM) as a &apos;'push'&apos; or as a &apos;'pull'&apos; change methodology. &apos;'Push'&apos; is the operational improvement role of TQM; &apos;'pull'&apos; is the strategic or direction giving, improvement role of TQM. Following the onset of privatisation in 1990 there has been evidence of the RECs adopting TQM in both &apos;'push'&apos; and &apos;'pull'&apos; methodologies with varying degrees of success. An evaluation of the change processes involved will enable improved change models to be developed leading to increased business effectiveness in this 30 billion pounds sterling industry. Other possible benefits include the possible generalisations to other utilities such as water, roads, gas and telecoms. The research methodology includes a comparative case study analysis of five RECs, which have used TQM as their overarching approach to change. One of the cases is analysed to a more in-depth level based on the multiple case findings. The findings indicate that the &apos;'push-pull'&apos; analysis enables the full range of TQM activities to be evaluated in the RECs studied. Overall, there is a need to have a balanced portfolio of operational or &apos;'push'&apos;-based TQM activity that is driven by strategic or &apos;'pull'&apos; based TQM planning and activity. (author)

  14. Human FAD synthase (isoform 2): a component of the machinery that delivers FAD to apo-flavoproteins. (United States)

    Torchetti, Enza M; Bonomi, Francesco; Galluccio, Michele; Gianazza, Elisabetta; Giancaspero, Teresa A; Iametti, Stefania; Indiveri, Cesare; Barile, Maria


    A soluble form of human FAD synthase (isoform 2; hFADS2) was produced and purified to homogeneity as a recombinant His-tagged protein. The enzyme binds 1 mole of the FAD product very tightly, although noncovalently. Complete release of FAD from the 'as isolated' protein requires extensive denaturation. A 75 : 25 mixture of apo/holoprotein could be prepared by treatment with mild chaotropes, allowing estimatation of the contribution made by bound FAD to the protein stability and evaluatation of whether structural rearrangements may be required for FAD release. Under turnover conditions, the enzyme catalyzes FAD assembly from ATP and FMN and, at a much lower rate, the pyrophosphorolytic hydrolysis of FAD. Several mechanistic features of both reactions were investigated in detail, along with their dependence on environmental conditions (pH, temperature, dependence on metals). Our data indicate that FAD release may represent the rate-limiting step of the whole catalytic cycle and that the process leading to FAD synthesis, and delivery to client apoproteins may be tightly controlled.

  15. Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory. (United States)

    Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D'Adamio, Luciano


    Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16-17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16-17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers.

  16. Gold nanoparticles&apos; blocking effect on UV-induced damage to human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Calzolai, Luigi, E-mail:; Laera, Stefania; Ceccone, Giacomo; Gilliland, Douglas [Institute for Health and Consumer Protection, European Commission, Joint Research Centre (Italy); Hussain, Rohanah; Siligardi, Giuliano [Diamond Light Source (United Kingdom); Rossi, Francois [Institute for Health and Consumer Protection, European Commission, Joint Research Centre (Italy)


    Ultraviolet radiation can cause the unfolding and destabilization of proteins. By using high energy photons from a synchrotron radiation source, we show that the UV-induced destabilization of human serum albumin (HSA) can be detected and monitored by measuring the circular dichroism spectrum of the protein. The high flux radiation source damages the HSA protein by causing a partial unfolding of the protein and a significant reduction in the amount of its secondary structure. Gold nanoparticles can effectively stop this UV-induced unfolding of HSA caused by synchrotron radiation. These phenomena could offer interesting applications to protect HSA protein from UV-induced damage and provide an alternative method to measure the relative stability of HSA.

  17. Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity. (United States)

    Soerensen, Mette; Dato, Serena; Tan, Qihua; Thinggaard, Mikael; Kleindorp, Rabea; Beekman, Marian; Suchiman, H Eka D; Jacobsen, Rune; McGue, Matt; Stevnsner, Tinna; Bohr, Vilhelm A; de Craen, Anton J M; Westendorp, Rudi G J; Schreiber, Stefan; Slagboom, P Eline; Nebel, Almut; Vaupel, James W; Christensen, Kaare; Christiansen, Lene


    In this study, we investigated 102 single-nucleotide polymorphisms (SNPs) covering the common genetic variation in 16 genes recurrently regarded as candidates for human longevity: APOE; ACE; CETP; HFE; IL6; IL6R; MTHFR; TGFB1; APOA4; APOC3; SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. In a case-control study of 1,089 oldest-old (ages 92-93) and 736 middle-aged Danes, the minor allele frequency (MAF) of rs769449 (APOE) was significantly decreased in the oldest-old, while the MAF of rs9923854 (CETP) was significantly enriched. These effects were supported when investigating 1,613 oldest-old (ages 95-110) and 1,104 middle-aged Germans. rs769449 was in modest linkage equilibrium (R (2)=0.55) with rs429358 of the APOE-ε4 haplotype and adjusting for rs429358 eliminated the association of rs769449, indicating that the association likely reflects the well-known effect of rs429358. Gene-based analysis confirmed the effects of variation in APOE and CETP and furthermore pointed to HSPA14 as a longevity gene. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes, only one SNP, rs2069827 (IL6), was borderline significantly associated with survival from age 92 (P-corrected=0.064). This advantageous effect of the minor allele was supported when investigating a Dutch longitudinal cohort (N=563) of oldest-old (age 85+). Since rs2069827 was located in a putative transcription factor binding site, quantitative RNA expression studies were conducted. However, no difference in IL6 expression was observed between rs2069827 genotype groups. In conclusion, we here support and expand the evidence suggesting that genetic variation in APOE, CETP, and IL6, and possible HSPA14, is associated with human longevity.

  18. Disruption of arterial perivascular drainage of amyloid-β from the brains of mice expressing the human APOE ε4 allele.

    Directory of Open Access Journals (Sweden)

    Cheryl A Hawkes

    Full Text Available Failure of elimination of amyloid-β (Aβ from the brain and vasculature appears to be a key factor in the etiology of sporadic Alzheimer's disease (AD and cerebral amyloid angiopathy (CAA. In addition to age, possession of an apolipoprotein E (APOE ε4 allele is a strong risk factor for the development of sporadic AD. The present study tested the hypothesis that possession of the APOE ε4 allele is associated with disruption of perivascular drainage of Aβ from the brain and with changes in cerebrovascular basement membrane protein levels. Targeted replacement (TR mice expressing the human APOE3 (TRE3 or APOE4 (TRE4 genes and wildtype mice received intracerebral injections of human Aβ(40. Aβ(40 aggregated in peri-arterial drainage pathways in TRE4 mice, but not in TRE3 or wildtype mice. The number of Aβ deposits was significantly higher in the hippocampi of TRE4 mice than in the TRE3 mice, at both 3- and 16-months of age, suggesting that clearance of Aβ was disrupted in the brains of TRE4 mice. Immunocytochemical and Western blot analysis of vascular basement membrane proteins demonstrated significantly raised levels of collagen IV in 3-month-old TRE4 mice compared with TRE3 and wild type mice. In 16-month-old mice, collagen IV and laminin levels were unchanged between wild type and TRE3 mice, but were lower in TRE4 mice. The results of this study suggest that APOE4 may increase the risk for AD through disruption and impedance of perivascular drainage of soluble Aβ from the brain. This effect may be mediated, in part, by changes in age-related expression of basement membrane proteins in the cerebral vasculature.

  19. Nanosized fibers&apos; effect on adult human articular chondrocytes behavior

    Energy Technology Data Exchange (ETDEWEB)

    Stenhamre, Hanna [Biopolymer Technology, Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg (Sweden); Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg (Sweden); Thorvaldsson, Anna, E-mail: [Biopolymer Technology, Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg (Sweden); Swerea IVF, Mölndal (Sweden); Enochson, Lars [Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg (Sweden); Walkenström, Pernilla [Swerea IVF, Mölndal (Sweden); Lindahl, Anders [Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg (Sweden); Brittberg, Mats [Cartilage Research Unit, University of Gothenburg, Department Orthopaedics, Kungsbacka Hospital, Kungsbacka (Sweden); Gatenholm, Paul [Biopolymer Technology, Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg (Sweden)


    Tissue engineering with chondrogenic cell based therapies is an expanding field with the intention of treating cartilage defects. It has been suggested that scaffolds used in cartilage tissue engineering influence cellular behavior and thus the long-term clinical outcome. The objective of this study was to assess whether chondrocyte attachment, proliferation and post-expansion re-differentiation could be influenced by the size of the fibers presented to the cells in a scaffold. Polylactic acid (PLA) scaffolds with different fiber morphologies were produced, i.e. microfiber (MS) scaffolds as well as nanofiber-coated microfiber scaffold (NMS). Adult human articular chondrocytes were cultured in the scaffolds in vitro up to 28 days, and the resulting constructs were assessed histologically, immunohistochemically, and biochemically. Attachment of cells and serum proteins to the scaffolds was affected by the architecture. The results point toward nano-patterning onto the microfibers influencing proliferation of the chondrocytes, and the overall 3D environment having a greater influence on the re-differentiation. In the efforts of finding the optimal scaffold for cartilage tissue engineering, studies as the current contribute to the knowledge of how to affect and control chondrocytes behavior. - Highlights: ► Chondrocyte behavior in nanofiber-coated microfiber versus microfiber scaffolds ► High porosity (> 90%) and large pore sizes (a few hundred μm) of nanofibrous scaffolds ► Proliferation enhanced by presence of nanofibers ► Differentiation not significantly affected ► Cell attachment improved in presence of both nanofibers and serum.

  20. APO-9′-Fucoxanthinone Extracted from Undariopsis peteseniana Protects Oxidative Stress-Mediated Apoptosis in Cigarette Smoke-Exposed Human Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Jun-Ho Jang


    Full Text Available Long-term cigarette smoking increases the risk for chronic obstructive pulmonary disease (COPD, characterized by irreversible expiratory airflow limitation. The pathogenesis of COPD involves oxidative stress and chronic inflammation. Various natural marine compounds possess both anti-oxidant and anti-inflammatory properties, but few have been tested for their efficacy in COPD models. In this study, we conducted an in vitro screening test to identify natural compounds isolated from various brown algae species that might provide protection against cigarette smoke extract (CSE-induced cytotoxicity. Among nine selected natural compounds, apo-9′-fucoxanthinone (Apo9F exhibited the highest protection against CSE-induced cytotoxicity in immortalized human bronchial epithelial cells (HBEC2. Furthermore, the protective effects of Apo9F were observed to be associated with a significant reduction in apoptotic cell death, DNA damage, and the levels of mitochondrial reactive oxygen species (ROS released from CSE-exposed HBEC2 cells. These results suggest that Apo9F protects against CSE-induced DNA damage and apoptosis by regulating mitochondrial ROS production.

  1. APO-9′-Fucoxanthinone Extracted from Undariopsis peteseniana Protects Oxidative Stress-Mediated Apoptosis in Cigarette Smoke-Exposed Human Airway Epithelial Cells (United States)

    Jang, Jun-Ho; Lee, Ji-Hyeok; Chand, Hitendra S.; Lee, Jong-Soo; Lin, Yong; Weathington, Nathaniel; Mallampalli, Rama; Jeon, You-Jin; Nyunoya, Toru


    Long-term cigarette smoking increases the risk for chronic obstructive pulmonary disease (COPD), characterized by irreversible expiratory airflow limitation. The pathogenesis of COPD involves oxidative stress and chronic inflammation. Various natural marine compounds possess both anti-oxidant and anti-inflammatory properties, but few have been tested for their efficacy in COPD models. In this study, we conducted an in vitro screening test to identify natural compounds isolated from various brown algae species that might provide protection against cigarette smoke extract (CSE)-induced cytotoxicity. Among nine selected natural compounds, apo-9′-fucoxanthinone (Apo9F) exhibited the highest protection against CSE-induced cytotoxicity in immortalized human bronchial epithelial cells (HBEC2). Furthermore, the protective effects of Apo9F were observed to be associated with a significant reduction in apoptotic cell death, DNA damage, and the levels of mitochondrial reactive oxygen species (ROS) released from CSE-exposed HBEC2 cells. These results suggest that Apo9F protects against CSE-induced DNA damage and apoptosis by regulating mitochondrial ROS production. PMID:27455285

  2. Behavioral phenotype and BDNF differences related to apoE isoforms and sex in young transgenic mice

    DEFF Research Database (Denmark)

    Reverte, Ingrid; Klein, Anders Bue; Ratner, Cecilia


    Human apolipoprotein E (apoE) plays an important role in lipid transport and distribution, being involved in neurite growth and neuroprotection in the brain. In humans, the apoE4 isoform is a risk factor for developing Azheimer's disease (AD), while apoE2 seems to provide neuroprotection. However......, very little information is available on apoE2 genotype. In the present study, we have characterized behavioral and learning phenotypes in young transgenic mice apoE2, apoE3 and apoE4 of both sexes. We have also determined the levels of brain-derived neurotrophic factor (BDNF) and its receptor Trk......B in cortex and hippocampus of male and female mice carrying either genotype. Our results show a worse performance of apoE4 and apoE2 mice in the acquisition of a spatial task compared to apoE3 mice, and a worse retention in apoE2 mice compared to the other two genotypes. On the other hand, an increase...

  3. High-density lipoprotein apolipoprotein A-I kinetics in obesity. (United States)

    Ooi, Esther M M; Watts, Gerald F; Farvid, Maryam S; Chan, Dick C; Allen, Michael C; Zilko, Simon R; Barrett, P Hugh R


    Low plasma concentrations of high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I (apoA-I) are independent predictors of coronary artery disease and are often associated with obesity and the metabolic syndrome. However, the underlying kinetic determinants of HDL metabolism are not well understood. We pooled data from 13 stable isotope studies to investigate the kinetic determinants of apoA-I concentrations in lean and overweight-obese individuals. We also examined the associations of HDL kinetics with age, sex, BMI, fasting plasma glucose, fasting insulin, Homeostasis Model Assessment score, and concentrations of apoA-I, triglycerides, HDL-cholesterol and low-density lipoprotein-cholesterol. Compared with lean individuals, overweight-obese individuals had significantly higher HDL apoA-I fractional catabolic rate (0.21+/-0.01 vs. 0.33+/-0.01 pools/d; pModel Assessment score, HDL apoA-I PR was an independent predictor of apoA-I concentration. In overweight-obese subjects, hypercatabolism of apoA-I is paralleled by an increased production of apoA-I, with HDL apoA-I PR being the stronger determinant of apoA-I concentration. This could have therapeutic implications for the management of dyslipidemia in individuals with low plasma HDL-cholesterol.

  4. High energy X-ray laboratory &apos;'HEXYLab'&apos;. The new facility &apos;'HEXYTech'&apos;; Hochenergie-Roentgen-Labor &apos;'HEXYLab'&apos;. Die neue Anlage &apos;'HEXYTech'&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Redmer, Bernhard; Hohendorf, Stefan; Kolkoori, Sanjeevareddy; Wrobel, Norma; Ewert, Uwe [BAM Bundesanstalt fuer Materialforschung und -pruefung, Berlin (Germany)


    High-energy radiography is used traditionally for the detection of defects in the thick-walled, bulky components. It is also used for testing the integrity of components for civil and security related applications (containers). The combination of high-energy emitters with digital detector arrays or line cameras allows test procedures in a shorter time compared to film or higher contrast sensitivity. The high-energy X-ray laboratory HEXYLab BAM is a joint laboratory in which future users, manufacturers and scientists can initiate and develop joint development projects. The new universal manipulation system HEXYTech forms the engineering and technical base for the most diverse requirements in HEXYLab (High Energy X-raY Lab.). With a total of 13 rotary and linear axes the diverse trajectories for tube, object and detector can be programmed. So large objects with complex geometries can be examined. 2D and 3D images can be measured by simple radiography, and laminography and computed tomography. The general rules for the application of high energy radiography with digital detectors (imaging plates, Digital detector arrays) were determined within the framework of the European project &apos;'HEDRad'&apos; (High Energy Digital Radiography) and included in the standard DIN EN ISO 17636-2. This article gives an overview of the testing technology and presents the possible applications on the basis of images and experiments. (PowerPoint slides). [German] Hochenergie-Radiographie wird traditionell fuer die Detektion von Defekten in dickwandigen, sperrigen Komponenten angewendet. Sie wird auch genutzt fuer die Pruefung der Komponentenintegritaet bei zivilen und sicherheitsrelevanten Anwendungen (Container). Die Kombination von Hochenergie- Strahlern mit digitalen Detektorarrays oder Zeilenkameras ermoeglicht die Pruefungsdurchfuehrung in kuerzerer Zeit im Vergleich zum Film oder mit hoeherer Kontrastempfindlichkeit. Das Hochenergie-Roentgen-Labor &apos;'HEXYLab'&apos

  5. The effects of the apoE4 genotype on the developing mouse retina. (United States)

    Maharshak, Idit; Salomon-Zimri, Shiran; Antes, Ran; Liraz, Ori; Nisgav, Yael; Livnat, Tami; Weinberger, Dov; Colton, Carol A; Solomon, Arieh S; Michaelson, Daniel M


    Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with neuronal and vascular impairments. The retina, which is as an extension of the central nervous system (CNS), is a particularly suitable model for studying developmental and functional aspects of the neuronal and vascular systems. This study investigates the apoE4-dependent developmental effects on the retinal vasculature and neuronal systems and on the levels of apoE and the vascular endothelial growth factor (VEGF) in the retina. This was performed utilizing retinas of 4, 7, 12, and of 120-day-old human-apoE4-targeted replacement mice and of corresponding mice that express the AD benign isoform, apoE3. The results obtained revealed retinal vascular pathology in the apoE4 mice, which started on the early post-natal days. This includes transient increase in vascular branching, and vascular buds which are round vascular elements representing sprouting or retracting vessels. These effects peaked and ended during the neonatal period. Examination of the synaptic system utilizing the pre-synaptic marker synaptophysin revealed a significant decrease of retinal synaptic density in the apoE4 mice, which was detectable by post-natal day 12 (P12). These morphological changes are associated with neonatal age-dependent elevation in the apoE levels in both apoE3 and apoE4 retinas which is more profound in the apoE4 mice and a corresponding increase in VEGF levels, which is less profound in the apoE4 mice. Additionally, we observed lower levels of retinal VEGF in the apoE4 mice compared to the apoE3 mice retinas on P12. These results show that apoE4 has a transient vascular effect during retinal development that ends in the neonatal period, which is accompanied by a synaptic effect that begins at the end of the neonatal period. These findings show that the apoE4 genotype can have distinct developmental effects on both the retinal vasculature and on neurons and

  6. Experience of development and testing of a new model of an anthropomorphic radiodosimetric phantom of the human body ARDF-10 &apos;Roman&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Bruhov, R.E.; Finkel, F.V., E-mail:, E-mail: [STC RADEK, Russian Federation, Saint-Petersburg (Russian Federation)


    In 2006-2010 by the commission of the Radiation and Nuclear Safety Authority in Finland applied scientific research and development of a new model of an anthropomorphic radio dosimetric phantom of the human body (the Phantom) were performed, after the development of the production technology and initial testing in 2010-2012 the first serial copy of the Phantom under the name ARDF-10 ROMAN was produced. The main application of the new model of the Phantom ARDF-10 ROMAN: - increase of the precision of calibration and implementation of the periodic monitoring of Whole body counters (WBC) equipment, standardization of measurement procedure for inter-laboratory comparisons of the incorporated activity. - metrological support of the development and implementation of new methods for human radiation spectrometry: identification of radionuclide content of incorporated activity in the human body; measurements of the activity of incorporated technogenic and natural radionuclides in the whole body and in the lungs; measurements of {sup 90}Sr content in the bone tissue. Study of the mechanisms of the intake, distribution, accumulation and excretion of the radionuclides in the human body, such as: daughter products of {sup 222}Rn decay in the respiratory tract, {sup 241}Am, other transuranic elements; isotopes of iodine in the thyroid gland; radiopharmaceuticals administered to patients for diagnostic and medicinal purposes. Obtaining estimates of spatial-temporal distribution of individual internal exposure dose of a human. The result of the work of recent years has been the creation of hygienic safe standard sample of an anthropomorphic radio dosimetric phantom of the human body ARDF-10 ROMAN, consisting of 4 anthropometric models of body parts, which are independent assembly units (head phantom, neck phantom, torso phantom, knee phantom). Phantom models are made from simulators of bone, soft (muscle) and lungs biological tissue. The Phantom contains 28 separate elements. To

  7. High cell density and high expression of recombinant human ApoA-Imilano in Eschenichia coli by twice temperature-shifted induction

    Institute of Scientific and Technical Information of China (English)

    ZHUANG Yingping; MA Wenfeng; GUO Meijin; DING Mansheng; CHU Ju; ZHANG Siliang


    The effect of temperature on the formation of recombinant protein,apolipoprotein A-IMilano was investigated in the present study.The temperature of the initial growth phase was set at 30℃,while temperature variation in induction phase was arranged in three modes.High cell-density culture of Escherichia coli and high expression of recombinant human by twice temperature-shifted induction were carried out.Experimental results showed that ApoA-IMilano reached 4.8 g/L with the final cell density of OD600,150.It was found that twice temperature-shifted induction could successfully avoid the effect of acetic acid on cell density and the expression of the product.The present study provides a basic procedure for the production of recombinant ApoA-IMilano.

  8. Oil protection &apos;&apos;John R&apos;&apos;; Oljevernaksjon &apos;&apos;John R&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)



    The report briefly reviews the emergency actions after the bulk ship &apos;&apos;John R&apos;&apos; ran aground off Troms on December 15, 2002. The report was worked out by the contingency and control division at the National State Pollution Control Authority (SFT). SFT mobilized their own action organization to attend to the oil pollution preparedness around the disabled ship. The Norwegian Directorate of Shipping and Navigation (SD) mobilized in order to attend to a possible emergency discharging of the ship. In the opening phase, the situation was handled by Defence Command North Norway. The report is built on logs and other written documentation from the Coast Guard and from SFT. Material from several other participants are also included. The harmful effects on the environment were kept to a minimum. Altogether oil damage was observed on 1300 - 1800 sea birds. Only minor shores in three areas were affected.

  9. Crystal structures of human sulfotransferases SULT1B1 and SULT1C1 complexed with the cofactor product adenosine-3&apos;- 5&apos;-diphosphate (PAP)

    Energy Technology Data Exchange (ETDEWEB)

    Dombrovski, Luidmila; Dong, Aiping; Bochkarev, Alexey; Plotnikov, Alexander N. (Toronto)


    Cytosolic sulfotransferases (SULTs), often referred as Phase II enzymes of chemical defense, are a superfamily of enzymes that catalyze the transfer of a sulfonate group from 3{prime}-phosphoadenosine 5{prime}-phosphosulfate (PAPS) to an acceptor group of substrates. This reaction modulates the activities of a large array of small endogenous and foreign chemicals including drugs, toxic compounds, steroid hormones, and neurotransmitters. In some cases, however, SULTs activate certain food and environmental compounds to mutagenenic and carcinogenic metabolites. Twelve human SULTs have been identified, which are partitioned into three families: SULT1, SULT2 and SULT4. The SULT1 family is further divided in four subfamilies, A, B, C, and E, and comprises eight members (1A1, 1A2, 1A3, 1B1, 1C1, 1C2, 1C3, and 1E1). Despite sequence and structural similarity among the SULTs, the family and subfamily members appear to have different biological function. SULT1 family shows substrate-binding specificity for simple phenols, estradiol, and thyroid hormones, as well as environmental xenobiotics and drugs. Human SULT1B1 is expressed in liver, colon, small intestine, and blood leukocytes, and shows substrate-binding specificity to thyroid hormones and benzylic alcohols. Human SULT1C1 is expressed in the adult stomach, kidney, and thyroid, as well as in fetal kidney and liver. SULT1C1 catalyzes the sulfonation of p-nitrophenol and N-hydroxy-2-acetylaminofluorene in vitro. However, the in vivo function of the enzyme remains unknown. We intend to solve the structures for all of the SULTs for which structural information is not yet available, and compare the structural and functional features of the entire SULT superfamily. Here we report the structures of two members of SULT1 family, SULT1B1 and SULT1C1, both in complex with the product of the PAPS cofactor, adenosine-3{prime}-5{prime}-diphosphate (PAP).

  10. The national research project MURST/CNR-ENEA on the protection of the human being and environment from electromagnetic pollution; Il progetto nazionale di ricerca MURST/CNR-ENEA su Salvaguardia dell&apos;uomo e dell&apos;ambiente dalle emissioni elettromagnetiche

    Energy Technology Data Exchange (ETDEWEB)

    Musella, D. [Ministero delle Comunicazioni, Istituto Superiore delle Comunicazioni e delle Tecnologie dell' Informazione, Rome (Italy)


    Electric, magnetic and electromagnetic fields interact with the human body and other biological systems through a number of physical mechanisms. People are continually exposed to electric and magnetic fields arising from a wide variety of sources that use electrical energy at various frequencies and levels. At the same time, a great deal of speculation and research has occurred concerning possible health risks arising from exposure to electric and magnetic fields and to take the appropriate steps. Especially in the latest years, Italy has been very careful in the electromagnetic pollution problem. The Italian Environment Ministry has enacted the decree 381/98 on safety in electromagnetic fields (exposure limits and quality targets) related to communication systems. The Italian Senate is discussing about a new framework law to reorganize all the subject. On the scientific level a new project of research, called Project 5%, on the protection of the human being and environment has been planned. This paper offers an overview on Project 5%. [Italian] I campi elettrici, magnetici ed elettromagnetici interagiscono con il corpo umano e con altri sistemi biologici secondo alcuni fenomeni fisici. La popolazione e&apos; continuamente esposta a tali campi emessi da una moltitudine di sorgenti di diversa natura che utilizzano l&apos;energia elettromagnetica in varia misura e compresa in un largo spettro di frequenze. Ne consegue la necessita&apos; di studiare i possibili rischi per la salute umana e le contromisure adottabili. L&apos;Italia, soprattutto negli ultimi anni, si e&apos; dimostrata particolarmente sensibile al problema dell&apos;inquinamento EM. Il Ministero dell&apos;ambiente, con il decreto 381/98 ha definito i limiti di esposizione e gli obiettivi di qualita&apos; dei sistemi di telecomunicazione. Al Senato e&apos; in discussione una nuova legge quadro nazionale mirante al riordino della materia. Sul piano scientifico e&apos; recentemente partito un nuovo

  11. In LDL receptor-deficient mice, catabolism of remnant lipoproteins requires a high level of apoE but is inhibited by excess apoE

    NARCIS (Netherlands)

    Dijk, K.W. van; Vlijmen, B.J.M. van; Hof, H.B. van 't; Zee, A. van der; Santamarina-Fojo, S.; Berkel, T.J.C. van; Havekes, L.M.; Hofker, M.H.


    To investigate the quantitative requirement for apolipoprotein (apo) E in the clearance of lipoproteins via the non-low density lipoprotein (LDL) receptor mediated pathway, human APOE was overexpressed at various levels in the livers of mice deficient for both the endogenous Apoe and Ldlr genes

  12. Generation of human induced pluripotent stem cells from a Bombay individual: Moving towards &apos;universal-donor&apos; red blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Seifinejad, Ali; Taei, Adeleh [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Totonchi, Mehdi; Vazirinasab, Hamed [Department of Genetics, Royan Institute for Reproductive Biomedicine, ACECR, Tehran (Iran, Islamic Republic of); Hassani, Seideh Nafiseh [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Aghdami, Nasser [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Department of Regenerative Biomedicine, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Shahbazi, Ebrahim [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Yazdi, Reza Salman [Department of Genetics, Royan Institute for Reproductive Biomedicine, ACECR, Tehran (Iran, Islamic Republic of); Salekdeh, Ghasem Hosseini, E-mail: [Department of Molecular Systems Biology, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Department of Systems Biology, Agricultural Biotechnology Research Institute of Iran, Karaj (Iran, Islamic Republic of); Baharvand, Hossein, E-mail: [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Department of Regenerative Biomedicine, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Department of Developmental Biology, University of Science and Culture, ACECR, Tehran (Iran, Islamic Republic of)


    Bombay phenotype is one of the rare phenotypes in the ABO blood group system that fails to express ABH antigens on red blood cells. Nonsense or missense mutations in fucosyltransfrase1 (FUT1) and fucosyltransfrase2 (FUT2) genes are known to create this phenotype. This blood group is compatible with all other blood groups as a donor, as it does not express the H antigen on the red blood cells. In this study, we describe the establishment of human induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of a Bombay blood-type individual by the ectopic expression of established transcription factors Klf4, Oct4, Sox2, and c-Myc. Sequence analyses of fibroblasts and iPSCs revealed a nonsense mutation 826C to T (276 Gln to Ter) in the FUT1 gene and a missense mutation 739G to A (247 Gly to Ser) in the FUT2 gene in the Bombay phenotype under study. The established iPSCs resemble human embryonic stem cells in morphology, passaging, surface and pluripotency markers, normal karyotype, gene expression, DNA methylation of critical pluripotency genes, and in-vitro differentiation. The directed differentiation of the iPSCs into hematopoietic lineage cells displayed increased expression of the hematopoietic lineage markers such as CD34, CD133, RUNX1, KDR, {alpha}-globulin, and {gamma}-globulin. Such specific stem cells provide an unprecedented opportunity to produce a universal blood group donor, in-vitro, thus enabling cellular replacement therapies, once the safety issue is resolved.

  13. 13-hydroxy linoleic acid increases expression of the cholesterol transporters ABCA1, ABCG1 and SR-BI and stimulates apoA-I-dependent cholesterol efflux in RAW264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Kämmerer Ines


    Full Text Available Abstract Background Synthetic activators of peroxisome proliferator-activated receptors (PPARs stimulate cholesterol removal from macrophages through PPAR-dependent up-regulation of liver × receptor α (LXRα and subsequent induction of cholesterol exporters such as ATP-binding cassette transporter A1 (ABCA1 and scavenger receptor class B type 1 (SR-BI. The present study aimed to test the hypothesis that the hydroxylated derivative of linoleic acid (LA, 13-HODE, which is a natural PPAR agonist, has similar effects in RAW264.7 macrophages. Methods RAW264.7 macrophages were treated without (control or with LA or 13-HODE in the presence and absence of PPARα or PPARγ antagonists and determined protein levels of LXRα, ABCA1, ABCG1, SR-BI, PPARα and PPARγ and apolipoprotein A-I mediated lipid efflux. Results Treatment of RAW264.7 cells with 13-HODE increased PPAR-transactivation activity and protein concentrations of LXRα, ABCA1, ABCG1 and SR-BI when compared to control treatment (P Conclusion 13-HODE induces cholesterol efflux from macrophages via the PPAR-LXRα-ABCA1/SR-BI-pathway.

  14. Just Like All the Other Humans? Analyzing Images of Scientists in Children&apos;s Trade Books (United States)

    Rawson, Casey H.; McCool, Megan Astolfi


    Despite the efforts of researchers and national science organizations to recruit more women and minorities into the science and engineering workforce, these fields are still largely dominated by White males. Research suggests that children&apos;s mental prototypes of the scientist include a variety of negative and stereotypical features that may…

  15. Inhibition of apolipoprotein A-I gene expression by obesity-associated endocannabinoids. (United States)

    Haas, Michael J; Mazza, Angela D; Wong, Norman C W; Mooradian, Arshag D


    Obesity is associated with increased serum endocannabinoid (EC) levels and decreased high-density lipoprotein cholesterol (HDLc). Apolipoprotein A-I (apo A-I), the primary protein component of HDL is expressed primarily in the liver and small intestine. To determine whether ECs regulate apo A-I gene expression directly, the effect of the obesity-associated ECs anandamide and 2-arachidonylglycerol on apo A-I gene expression was examined in the hepatocyte cell line HepG2 and the intestinal cell line Caco-2. Apo A-I protein secretion was suppressed nearly 50% by anandamide and 2-arachidonoylglycerol in a dose-dependent manner in both cell lines. Anandamide treatment suppressed both apo A-I mRNA and apo A-I gene promoter activity in both cell lines. Studies using apo A-I promoter deletion constructs indicated that repression of apo A-I promoter activity by anandamide requires a previously identified nuclear receptor binding site designated as site A. Furthermore, anandamide-treatment inhibited protein-DNA complex formation with the site A probe. Exogenous over expression of cannabinoid receptor 1 (CBR1) in HepG2 cells suppressed apo A-I promoter activity, while in Caco-2 cells, exogenous expression of both CBR1 and CBR2 could repress apo A-I promoter activity. The suppressive effect of anandamide on apo A-I promoter activity in Hep G2 cells could be inhibited by CBR1 antagonist AM251 but not by AM630, a selective and potent CBR2 inhibitor. These results indicate that ECs directly suppress apo A-I gene expression in both hepatocytes and intestinal cells, contributing to the decrease in serum HDLc in obese individuals.

  16. Trimerization of apolipoprotein A-I retards plasma clearance and preserves antiatherosclerotic properties

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Laurberg, Jacob Marsvin; Andersen, Mikkel Holmen


    An increased plasma level of the major high-density lipoprotein (HDL) component, apolipoprotein A-I (apoA-I) is the aim of several therapeutic strategies for combating atherosclerotic disease. HDL therapy by direct intravenous administration of apoA-I is a plausible way; however, a fast renal...

  17. Apolipoproteins A-I and B in Kuwaiti children. (United States)

    Moussa, M A; Shaltout, A A; Nkansa-Dwamena, D; Mourad, M


    To assess the relation of apolipoproteins (Apos) A-I and B (the carrier proteins for high and low density lipoprotein cholesterol, respectively) with the degree of obesity, body fat distribution, serum lipids, glucose and insulin levels, a case-control study was carried out and included 460 Kuwaiti obese children, 6-13 years old, matched by age and sex to 460 normal-weight controls. Obese children were ascertained in a representative cross-sectional study of 2,400 school children. The Apo A-I levels were not different between obese and non-obese boys, while they were significantly lower in obese girls (p < 0.01). The Apo B mean concentrations were significantly higher in obese boys and girls (p < 0.001), while the Apo A-I:B ratio was significantly lower in obese children (p < 0.001). Apo A-I levels were positively correlated with total cholesterol, high- and low-density lipoprotein cholesterol, but were not correlated with very low-density lipoprotein cholesterol, triglycerides, insulin, glucose or insulin:glucose ratio. Apo B levels were negatively correlated with high-density lipoprotein cholesterol and positively correlated with insulin and insulin:glucose ratio (p < 0.01) in obese children. The study documented an adverse Apo profile in obese Kuwaiti children. Since Apo changes are correctable through management of obesity, their identification in childhood offers prospects for prevention of early onset atherogenesis in adulthood.

  18. 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.

  19. Structural and Functional Analysis of the ApolipoproteinA-I A164S Variant.

    Directory of Open Access Journals (Sweden)

    Jonathan Dalla-Riva

    Full Text Available Apolipoprotein A-I (apoA-I is the main protein involved in the formation of high-density lipoprotein (HDL, it is the principal mediator of the reverse cholesterol transfer (RCT pathway and provides cardio-protection. In addition to functional wild-type apoA-I, several variants have been shown to associate with hereditary amyloidosis. In this study we have performed biophysical and biochemical analyses of the structure and functional properties of the A164S variant of apoA-I (1:500 in the Danish general population, which is the first known mutation of apoA-I that leads to an increased risk of ischaemic heart disease (IHD, myocardial infarction and mortality without associated low HDL cholesterol levels. Despite the fact that epidemiologically IHD is associated with low plasma levels of HDL, the A164S mutation is linked to normal plasma levels of lipids, HDL and apoA-I, suggesting impaired functionality of this variant. Using biophysical techniques (e.g., circular dichroism spectroscopy and electron microscopy to determine secondary structure, stability and pro-amyloidogenic property of the lipid free A164S apoA-I variant, our observations suggest similarity in structural properties between apoA-I WT and apoA-I A164S. However, the A164S apoA-I variant exhibits lower binding affinity to lipids but forms similar sized HDL particles to those produced by WT.

  20. Proteomic analysis reveals the enhancement of human serum apolipoprotein A-1(APO A-1) in individuals infected with multiple dengue virus serotypes. (United States)

    Manchala, Nageswar Reddy; Dungdung, Ranjeet; Pilankatta, Rajendra


    Human serum protein profiling of the individual infected with multiple dengue virus serotypes for identifying the potential biomarkers and to investigate the cause for the severity of dengue virus infection. Dengue virus NS1-positive serum samples were pooled into two groups (S2 and S3) based on the molecular serotyping and number of heterotypic infections. The pooled serum samples were subjected to two-dimensional gel electrophoresis (2DGE) to identify the differentially expressed proteins. The peptide masses of upregulated protein were detected by matrix-assisted laser desorption-ionisation time-of-flight MALDI-TOF mass spectrometry and analysed by MASCOT search engine. The results were compared with the control group (S1). The commonly upregulated protein was validated by quantitative ELISA and compared with control as well as single serotypic infected samples. Based on 2DGE, total thirteen proteins were differentially upregulated in S2 and S3 groups as compared to control. Some of the upregulated proteins were involved in mediating the complement activation of immune response. The apolipoprotein A-1 (APO A-1) was upregulated in S2 and S3 groups. Upon validation, APO A-1 levels were increased in line with the number of heterotypic infection of dengue viruses. Heterotypic infection of dengue viruses upregulate the serum proteins involved in the complement pathway in the early phase of infection. There was a significant increase in the level of APO A-1 in three different serotypic infections of dengue virus as compared to control. Further, the role of APO-A1 can be explored in elucidating the mechanism of dengue pathogenesis. © 2017 John Wiley & Sons Ltd.

  1. NMR solution structures of the apo and peptide-inhibited human rhinovirus 3C protease (Serotype 14): structural and dynamic comparison. (United States)

    Bjorndahl, Trent C; Andrew, Lena C; Semenchenko, Valentyna; Wishart, David S


    The human rhinovirus (HRV) is a positive sense RNA virus responsible for about 30% of "common colds". It relies on a 182 residue cysteine protease (3C) to proteolytically process its single gene product. Inhibition of this enzyme in vitro and in vivo has consistently demonstrated cessation of viral replication. This suggests that 3C protease inhibitors could serve as good drug candidates. However, significant proteolytic substrate diversity exists within the 110+ known rhinovirus serotypes. To investigate this variability we used NMR to solve the structure of the rhinovirus serotype 14 3C protease (subgenus B) covalently bound to a peptide (acetyl-LEALFQ-ethylpropionate) inhibitor. The inhibitor-bound structure was determined to an overall rmsd of 0.82 A (backbone atoms) and 1.49 A (all heavy atoms). Comparison with the X-ray structure of the serotype 2 HRV 3C protease from subgenus A (51% sequence identity) bound to the inhibitor ruprintrivir allowed the identification of conserved intermolecular interactions involved in proximal substrate binding as well as subgenus differences that might account for the variability observed in SAR studies. To better characterize the 3C protease and investigate the structural and dynamic differences between the apo and bound states we also solved the solution structure of the apo form. The apo structure has an overall rmsd of 1.07 +/- 0.17 A over backbone atoms, which is greater by 0.25 A than what is seen for the inhibited enzyme (2B0F.pdb). This increase is localized to the enzyme's C-terminal beta-barrel domain, which is responsible for recognizing and binding proteolytic substrates. Amide hydrogen exchange dynamics revealed dramatic differences between the two enzyme states. Furthermore, a number of residues exhibited exchange-broadened amide NMR signals in the apo state compared to the inhibited state. The majority of these residues are associated with proteolytic substrate interaction.

  2. The &apos;mini&apos; and &apos;micro&apos; energy sources and their limitations; Les &apos;'minis'&apos; et &apos;'micros'&apos; sources d&apos;energie et leurs limites

    Energy Technology Data Exchange (ETDEWEB)



    The &apos;Science and defense 2003&apos; colloquium took place in Paris on December 2 and 3. It was organized by the general delegation of armament (DGA), the French atomic energy commission (CEA) with the participation of the national center of scientific research (CNRS) and the French ministry of research and new technologies. The main topic was the needs and the solutions implemented in the domain of energy sources both for civil and military portable applications. This article make a general summary of the content of this colloquium only in the domain of small power energy sources: emergence of new miniaturized portable devices (phones, computers, cameras, autonomous medical systems, wireless communication systems, soldiers equipments, drones etc..), improvement of batteries energy density and price, new needs linked with new functionalities, technological challenges (energy generation and recovery systems, miniaturized fuel-cells, use of recoverable energy sources, implantation of power sources in the human body etc..), new technological files (new electrode materials, micron- or sub-micron scale mechanical and electronic components, sensors, micro-motors, transfer of microelectronics technologies, hybrid systems..), international competition. (J.S.)

  3. Off-target effects of thrombolytic drugs: apolipoprotein A-I proteolysis by alteplase and tenecteplase. (United States)

    Gomaraschi, Monica; Ossoli, Alice; Vitali, Cecilia; Pozzi, Silvia; Vitali Serdoz, Laura; Pitzorno, Cristina; Sinagra, Gianfranco; Franceschini, Guido; Calabresi, Laura


    The administration of thrombolytic drugs is of proven benefit in a variety of clinical conditions requiring acute revascularization, including acute myocardial infarction (AMI), ischemic stroke, pulmonary embolism, and venous thrombosis. Generated plasmin can degrade non-target proteins, including apolipoprotein A-I (apoA-I), the major protein constituent of high-density lipoproteins (HDL). Aim of the present study was to compare the extent of apoA-I proteolytic degradation in AMI patients treated with two thrombolytic drugs, alteplase and the genetically engineered t-PA variant tenecteplase. ApoA-I degradation was evaluated in sera from 38 AMI patients treated with alteplase or tenecteplase. In vitro, apoA-I degradation was tested by incubating control sera or purified HDL with alteplase or tenecteplase at different concentrations (5-100 μg/ml). Treatment with alteplase and tenecteplase results in apoA-I proteolysis; the extent of apoA-I degradation was more pronounced in alteplase-treated patients than in tenecteplase-treated patients. In vitro, the extent of apoA-I proteolysis was higher in alteplase-treated sera than in tenecteplase-treated sera, in the whole drug concentration range. No direct effect of the two thrombolytic agents on apoA-I degradation was observed. In addition to apoA-I, apoA-IV was also degraded by the two thrombolytic agents and again proteolytic degradation was higher with alteplase than tenecteplase. In conclusion, this study indicates that both alteplase and tenecteplase cause plasmin-mediated proteolysis of apoA-I, with alteplase resulting in a greater apoA-I degradation than tenecteplase, potentially causing a transient impairment of HDL atheroprotective functions.

  4. The &apos;'invisible'&apos; radioactive scale

    Energy Technology Data Exchange (ETDEWEB)

    Bjoernstad, T.; Ramsoey, T


    Production and up-concentration of naturally occurring radioactive material (NORM) in the petroleum industry has attracted steadily increasing attention during the last 15 years. Most production engineers today associate this radioactivity with precipitates (scales) and sludges in production tubing, pumps, valves, separators, settling tanks etc., wherever water is being transported or treated. {sup 226}Ra and {sup 228}Ra are the most well known radioactive constituents in scale. Surprisingly little known is the radioactive contamination by {sup 210}Pb and progeny {sup 210}Bi and {sup 210}Po. These are found in combination with {sup 226}Ra in ordinary scale, often in layer of non-radioactive metallic lead in water transportation systems, but also in pure gas and condensate handling systems &apos;'unsupported'&apos; by {sup 226}Ra, but due to transportation and decay of the noble gas {sup 222}Rn in NG/LNG. This latter contamination may be rather thin, in some cases virtually invisible. When, in addition, the radiation energies are low enough for not being detectable on the equipment outer surface, its existence has for most people in the industry been a secret. The report discusses transportation and deposition mechanisms, detection methods and provides some examples of measured results from the North Sea on equipment sent for maintenance. It is concluded that a regular measurement program for this type of contamination should be mandatory under all dismantling processes of transportation and fluid handling equipment for fluids and gases offshore and onshore.

  5. Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy? (United States)

    Jasienska, Grazyna; Ellison, Peter T; Galbarczyk, Andrzej; Jasienski, Michal; Kalemba-Drozdz, Malgorzata; Kapiszewska, Maria; Nenko, Ilona; Thune, Inger; Ziomkiewicz, Anna


    The alleles that are detrimental to health, especially in older age, are thought to persist in populations because they also confer some benefits for individuals (through antagonistic pleiotropy). The ApoE4 allele at the ApoE locus, encoding apolipoprotein E (ApoE), significantly increases risk of poor health, and yet it is present in many populations at relatively high frequencies. Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele? ApoE is a major supplier of cholesterol precursor for the production of ovarian oestrogen and progesterone, thus ApoE has been suggested as the potential candidate gene that may cause variation in reproductive performance. Our results support this hypothesis showing that in 117 regularly menstruating women those with genotypes with at least one ApoE4 allele had significantly higher levels of mean luteal progesterone (144.21 pmol l(-1)) than women with genotypes without ApoE4 (120.49 pmol l(-1)), which indicates higher potential fertility. The hormonal profiles were based on daily data for entire menstrual cycles. We suggest that the finding of higher progesterone in women with ApoE4 allele could provide first strong evidence for an evolutionary mechanism of maintaining the ancestral and health-worsening ApoE4 allele in human populations.

  6. Neutrino-gaseous &apos;'pancakes'&apos; and the problem of hidden mass

    Energy Technology Data Exchange (ETDEWEB)

    Doroshkevich, A.G. (AN SSSR, Moscow. Inst. Prikladnoj Matematiki)


    Taking into account peculiar velocities of neutrinos the gaseous component is shown to dominate in the central part of a cosmological &apos;'pancake'&apos; (rhosub(p) > rhosub(, while on the average anti rhosub(b) << anti rhosub( Therefore fragmentation of a gaseous &apos;'pancake'&apos; and later clustering of the fragments into galaxies and groups of galaxies are determined by velocity distribution and gravity of the gaseous component. The hidden mass is formed by capture of neutrinos by clustering clouds. Formation of the cluster of galaxies is connected with perturbations embracing all the neutrino-gaseous &apos;'pancake'&apos;, initial ratio of neutrino-to-gaseous densities being reestablished. It is shown that the first &apos;'pancakes'&apos; were formed at the red shifts z=5-8.

  7. ApoE knockout and knockin mice: the history of their contribution to the understanding of atherogenesis. (United States)

    Getz, Godfrey S; Reardon, Catherine A


    ApoE is a multifunctional protein that is expressed by many cell types that influences many aspects of cardiovascular physiology. In humans, there are three major allelic variants that differentially influence lipoprotein metabolism and risk for the development of atherosclerosis. Apoe-deficient mice and human apoE isoform knockin mice, as well as hypomorphic Apoe mice, have significantly contributed to our understanding of the role of apoE in lipoprotein metabolism, monocyte/macrophage biology, and atherosclerosis. This brief history of these mouse models will highlight their contribution to the understanding of the role of apoE in these processes. These Apoe(-/-) mice have also been extensively utilized as an atherosensitive platform upon which to assess the impact of modulator genes on the development and regression of atherosclerosis.

  8. Optimal strategies for the abatement of gaseous air pollutant emissions produced by human mobility. The Rome case study; Strategie ottimali per la riduzione delle emissioni di inquinanti gassosi prodotte dalla mobilita&apos; urbana. Un&apos;applicazione al caso di Roma

    Energy Technology Data Exchange (ETDEWEB)

    Santostefano, S.; Cirillo, M.C. [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Ambiente


    In this paper a cost-effectiveness of gaseous vehicular emission reduction has been carried out for human mobility, over the transport network in Rome: in other words, once a reduction target of total emissions has been fixed for each pollutant, the most efficient abatement measures from a technical-economic point of view are selected. The optimization problem has been formalized considering linear functions both for the objective function and for constrains, i.e. within the classic linear programming framework, the objective being that of finding the diversion of present vehicular traffic to alternative technologies with lower emissions at minimum costs. A set of transport alternative measures has been considered and emission abatement cost minimization has been assumed as an objective function; specified abatements for CO (Carbon monoxide), NO{sub x} (nitrogen oxides) and VOC (Volatile Organic Compounds) emissions have been introduced as constraints to the problem, expressed as reduction rates of estimated present emissions in the considered area. Model results show the distribution of present transportation capacity among possible alternatives for different hypothesis of emission reduction rates (reduction of 25%, 50%, 75%, 85% of present emissions and maximum feasible reduction within the specified constraints), and related costs. [Italian] In questo rapporto e&apos; stata condotta un&apos;analisi costi-efficacia relativa alla riduzione delle emissioni gassose veicolari dovute alla mobilita&apos; urbana sulla rete di trasporto di Roma: in altre parole, fissata una quota di abbattimento delle emissioni complessive per ogni inquinante, sono state individuate le misure piu&apos; efficienti dal punto di vista tecnico-economico che permettono di perseguire la riduzione prefissata. Il problema di ottimizzazione e&apos; stato formalizzato definendo sia la funzione obiettivo che i relativi vincoli come funzioni lineari, e quindi nell&apos;ambito della programmazione

  9. Characterization and behavior in the environment of the crude oil &apos;'Prestige'&apos;; Caracterisation et comportement dans l&apos;environnement du fioul &apos;'Prestige'&apos;

    Energy Technology Data Exchange (ETDEWEB)



    This study presents analysis realized on the crude oil of the tanker &apos;'Prestige'&apos; which sunk the 19 november 2002. The specifications on the product and its behavior in sea water are detailed. All the analysis are compared to the &apos;'Erika'&apos; crude oil. (A.L.B.)

  10. Pharmaceutical induction of ApoE secretion by multipotent mesenchymal stromal cells (MSCs

    Directory of Open Access Journals (Sweden)

    Whitney Mandolin J


    Full Text Available Abstract Background Apolipoprotein E (ApoE is a molecular scavenger in the blood and brain. Aberrant function of the molecule causes formation of protein and lipid deposits or "plaques" that characterize Alzheimer's disease (AD and atherosclerosis. There are three human isoforms of ApoE designated ε2, ε3, and ε4. Each isoform differentially affects the structure and function of the protein and thus the development of disease. Homozygosity for ApoE ε4 is associated with atherosclerosis and Alzheimer's disease whereas ApoE ε2 and ε3 tend to be protective. Furthermore, the ε2 form may cause forms of hyperlipoproteinemia. Therefore, introduction of ApoE ε3 may be beneficial to patients that are susceptible to or suffering from these diseases. Mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs are adult progenitor cells found in numerous tissues. They are easily expanded in culture and engraft into host tissues when administered appropriately. Furthermore, MSCs are immunosuppressive and have been reported to engraft as allogeneic transplants. In our previous study, mouse MSCs (mMSCs were implanted into the brains of ApoE null mice, resulting in production of small amounts of ApoE in the brain and attenuation of cognitive deficits. Therefore human MSCs (hMSCs are a promising vector for the administration of ApoE ε3 in humans. Results Unlike mMSCs, hMSCs were found not to express ApoE in culture; therefore a molecular screen was performed for compounds that induce expression. PPARγ agonists, neural stem cell conditioned medium, osteo-inductive media, dexamethasone, and adipo-inductive media (AIM were tested. Of the conditions tested, only AIM or dexamethasone induced sustained secretion of ApoE in MSCs and the duration of secretion was only limited by the length of time MSCs could be sustained in culture. Upon withdrawal of the inductive stimuli, the ApoE secretion persisted for a further 14 days. Conclusion The data

  11. Development and deployment of a novel &apos;'yellow'&apos; demulsifier for the gullfaks &apos;'A'&apos; platform

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, S.J.; Ingebrigtsen, T.; Breen, P.J.; Waage, J.; Thorstenson, T.; Melby, S.


    Oil producers are increasingly under pressure to produce their product in an environmentally sound manner. Releases to the environment are undesirable and, where permitted to make such releases, oil producers should minimise their environmental impact. The bulk of treatment chemicals designed to improve separation and provide clean water for disposal can themselves be harmful to the environment and must conform to very stringent rules to be considered environmentally acceptable, or &apos;'green'&apos;. Here we present data on the development of a green demulsifier for Statoil&apos;s Gullfaks &apos;'A'&apos; platform, which not only meets the very stringent regulations but also exhibits a significant improvement in product performance. While the&apos;&apos;bottle test&apos;&apos; remains the industry standard method for selecting demulsifiers, in recent years the &apos;&apos;mini trial&apos;&apos; method for product selection has gained favour. We describe using a combination of both methods for the development of the novel demulsifier technology described here. (Author) (tk)

  12. DEPTOR-related mTOR suppression is involved in metformin&apos;s anti-cancer action in human liver cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya, E-mail:


    Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin&apos;s anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin&apos;s anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin&apos;s anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin&apos;s anti-cancer action.

  13. Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPL

    NARCIS (Netherlands)

    Westerterp, M.; Haan, W. de; Berbée, J.F.P.; Havekes, L.M.; Rensen, P.C.N.


    Previous studies have shown that overexpression of human apolipoprotein C-I (apoC-I) results in moderate hypercholesterolemia and severe hypertriglyceridemia in mice in the presence and absence of apoE. We assessed whether physiological endogenous apoC-I levels are sufficient to modulate plasma

  14. &apos;&apos;de novo&apos;&apos; aneurysms following endovascular procedures

    Energy Technology Data Exchange (ETDEWEB)

    Briganti, F.; Cirillo, S.; Caranci, F. [Department of Neurological Sciences, Services of Neuroradiology, ' ' Federico II' ' University, Naples (Italy); Esposito, F.; Maiuri, F. [Department of Neurological Sciences, Services of Neurosurgery, ' ' Federico II' ' University, Naples (Italy)


    Two personal cases of &apos;&apos;de novo&apos;&apos; aneurysms of the anterior communicating artery (ACoA) occurring 9 and 4 years, respectively, after endovascular carotid occlusion are described. A review of the 30 reported cases (including our own two) of &apos;&apos;de novo&apos;&apos; aneurysms after occlusion of the major cerebral vessels has shown some features, including a rather long time interval after the endovascular procedure of up to 20-25 years (average 9.6 years), a preferential ACoA (36.3%) and internal carotid artery-posterior communicating artery (ICA-PCoA) (33.3%) location of the &apos;&apos;de novo&apos;&apos; aneurysms, and a 10% rate of multiple aneurysms. These data are compared with those of the group of reported spontaneous &apos;&apos;de novo&apos;&apos; aneurysms after SAH or previous aneurysm clipping. We agree that the frequency of &apos;&apos;de novo&apos;&apos; aneurysms after major-vessel occlusion (two among ten procedures in our series, or 20%) is higher than commonly reported (0 to 11%). For this reason, we suggest that patients who have been submitted to endovascular major-vessel occlusion be followed up for up to 20-25 years after the procedure, using non-invasive imaging studies such as MR angiography and high-resolution CT angiography. On the other hand, periodic digital angiography has a questionable risk-benefit ratio; it may be used when a &apos;&apos;de novo&apos;&apos; aneurysm is detected or suspected on non-invasive studies. The progressive enlargement of the ACoA after carotid occlusion, as described in our case 1, must be considered a radiological finding of risk for &apos;&apos;de novo&apos;&apos; aneurysm formation. (orig.)

  15. Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans. (United States)

    Lähdesmäki, Katariina; Öörni, Katariina; Alanne-Kinnunen, Mervi; Jauhiainen, Matti; Hurt-Camejo, Eva; Kovanen, Petri T


    Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions.

  16. Effect of mitochondrial, APOE, ACE and NOS3 gene polymorphisms on cardiovascular risk factors among the Vaqueiros de Alzada, a Northern Spain human isolate. (United States)

    Gómez, Pedro; Gómez, Juan; Corao, Ana I; De Canga, Julio; Coto, Eliecer


    The Vaqueiros de Alzada are a human isolate from Asturias, a Northern Spain region. Several hypotheses have been proposed to explain the origin of Vaqueiros. To determine whether the Vaqueiros and non-Vaqueiros from the same region have different genetic backgrounds, this study analysed nine mtDNA polymorphisms that define the common European mitochondrial haplogroups in a cohort of Vaqueiros (n = 60) and non-Vaqueiros (n = 110). Haplogroup H was the most frequent in Vaqueiros (42%) and non-Vaqueiros (46%). A total of 37% Vaqueiros were H1, compared to 31% of the non-Vaqueiros. This study also genotyped the two groups for three polymorphisms at the NOS3. APOE and ACE genes, that have previously been linked to risk of cardiovascular diseases. Allele and genotype frequencies did not differ between Vaqueiros and non-Vaqueiros. In addition, none of these polymorphisms were related to risk of hypertension, diabetes or hypercholesterolaemia in the two groups. The data suggested that Vaqueiros share the main haplogroup distribution as their non-Vaqueiros neighbours and other Cantabrian populations. In addition, no effect of the mitochondrial, NOS3. APOE and ACE polymorphisms on cardiovascular risk factors was observed.


    Energy Technology Data Exchange (ETDEWEB)

    Cresci, G.; Mannucci, F. [INAF-Osservatorio Astrofisco di Arcetri, largo E. Fermi 5, I-50127, Firenze (Italy); Mainieri, V. [European Southern Observatory, Karl-Schwarzschild-strasse 2, D-85748 Garching bei München (Germany); Brusa, M.; Perna, M.; Lanzuisi, G. [Dipartimento di Fisica e Astronomia, Università di Bologna, viale Berti Pichat 6/2, I-40127 Bologna (Italy); Marconi, A. [Dipartimento di Fisica e Astronomia, Università degli Studi di Firenze, via G. Sansone 1, I-50019 Sesto, Firenze (Italy); Piconcelli, E.; Feruglio, C.; Fiore, F.; Bongiorno, A. [INAF-Osservatorio Astronomico di Roma, via Frascati 33, I-00040 Monteporzio Catone (Italy); Maiolino, R. [Cavendish Laboratory, University of Cambridge, 19 J. J. Thomson Avenue, Cambridge (United Kingdom); Merloni, A [Max Planck Institut für Extraterrestrische Physik, Giessenbachstrasse 1, D-85748 Garching bei München (Germany); Schramm, M.; Silverman, J. D. [Kavli Institute for the Physics and Mathematics of the Universe (WPI), Todai Institutes for Advanced Study, the University of Tokyo, Kashiwanoha 5-1-5, Kashiwa-shi, Chiba 277-8568 (Japan); Civano, F., E-mail: [Department of Physics and Yale Center for Astronomy and Astrophysics, Yale University, PO Box 208121, New Haven, CT 06520-8121 (United States)


    Quasar feedback in the form of powerful outflows is invoked as a key mechanism to quench star formation in galaxies, preventing massive galaxies to overgrow and producing the red colors of ellipticals. On the other hand, some models are also requiring &apos;'positive'&apos; active galactic nucleus feedback, inducing star formation in the host galaxy through enhanced gas pressure in the interstellar medium. However, finding observational evidence of the effects of both types of feedback is still one of the main challenges of extragalactic astronomy, as few observations of energetic and extended radiatively driven winds are available. Here we present SINFONI near infrared integral field spectroscopy of XID2028, an obscured, radio-quiet z = 1.59 QSO detected in the XMM-COSMOS survey, in which we clearly resolve a fast (1500 km s{sup –1}) and extended (up to 13 kpc from the black hole) outflow in the [O III] lines emitting gas, whose large velocity and outflow rate are not sustainable by star formation only. The narrow component of Hα emission and the rest frame U-band flux from Hubble Space Telescope/Advanced Camera for Surveys imaging enable to map the current star formation in the host galaxy: both tracers independently show that the outflow position lies in the center of an empty cavity surrounded by star forming regions on its edge. The outflow is therefore removing the gas from the host galaxy (&apos;&apos;negative feedback&apos;&apos;), but also triggering star formation by outflow induced pressure at the edges (&apos;&apos;positive feedback&apos;&apos;). XID2028 represents the first example of a host galaxy showing both types of feedback simultaneously at work.

  18. Automated power system for the amplification module of the &apos;'Del'fin'&apos; high power laser. Avtomatizatsiia sistemy energopitaniia usilitel&apos;nogo modulia moshchnoi lazernoi ustanovki &apos;'Del&apos;fin

    Energy Technology Data Exchange (ETDEWEB)

    Allin, A.P.; Doroshkevich, I.L.; Kuchinskii, A.G.; Savchenko, V.M.; Senatskii, U.V.; Sklizkov, G.V.; Subbotin, L.K.; Taranchuk, V.B.


    An automated power supply subsystem in the &apos;'Del'fin'&apos; laser apparatus is described that uses a minicomputer on-line with a KAMAK device. Programs are given that are used with the automated power supply for the amplification module of the &apos;'Delfin'&apos; high power laser device for performing the functions of operational monitoring and control and the collection and preliminary processing of information arriving from the capacitor banks and the control components.

  19. ApoE polymorphisms in narcolepsy

    Directory of Open Access Journals (Sweden)

    Kasten Meike


    Full Text Available Summary Background Narcolepsy is a common neuropsychiatric disorder characterized by increased daytime sleepiness, cataplexy and hypnagogic hallucinations. Deficiency of the hypocretin neurotransmitter system was shown to be involved in the pathogenesis of narcolepsy in animals and men. There are several hints that neurodegeneration of hypocretin producing neurons in the hypothalamus is the pathological correlate of narcolepsy. The ApoE4 allele is a major contributing factor to early-onset neuronal degeneration in Alzheimer disease and other neurodegenerative diseases as well. Methods To clarify whether the ApoE4 phenotype predisposes to narcolepsy or associates with an earlier disease onset, we have genotyped the ApoE gene in 103 patients with narcolepsy and 101 healthy controls. Results The frequency of the E4 allele of the ApoE gene was 11% in the patient and 15% in the control groups. Furthermore, the mean age of onset did not differ between the ApoE4+ and ApoE4- patient groups. Conclusion Our results exclude the ApoE4 allele as a major risk factor for narcolepsy.

  20. apoE4近交系转基因鼠的高脂血症表现和自发变换行为损害%The Hyperlipidemia and Spontaneous Alternation Behavior Impairment in Human Apolipoprotein E4 (apoE4) Inbred Transgenic Mice

    Institute of Scientific and Technical Information of China (English)

    薛越强; 屠亚军; 杨鹏; 蒋效松; 廖峥嵘; 琦祖和



  1. &apos;&apos;When Cost Measures Contradict&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Montgomery, W. D.; Smith, A. E.; Biggar, S. L.; Bernstein, P. M.


    When regulators put forward new economic or regulatory policies, there is a need to compare the costs and benefits of these new policies to existing policies and other alternatives to determine which policy is most cost-effective. For command and control policies, it is quite difficult to compute costs, but for more market-based policies, economists have had a great deal of success employing general equilibrium models to assess a policy&apos;s costs. Not all cost measures, however, arrive at the same ranking. Furthermore, cost measures can produce contradictory results for a specific policy. These problems make it difficult for a policy-maker to determine the best policy. For a cost measures to be of value, one would like to be confident of two things. First one wants to be sure whether the policy is a winner or loser. Second, one wants to be confident that a measure produces the correct policy ranking. That is, one wants to have confidence in a policy measure&apos;s ability to correctly rank policies from most beneficial to most harmful. This paper analyzes empirically these two properties of different costs measures as they pertain to assessing the costs of the carbon abatement policies, especially the Kyoto Protocol, under alternative assumptions about implementation.

  2. Korea&apos;s 1-watt plan &apos;&apos;Standby Korea 2010&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yungrae


    Korea announced standby power of all electronics shall be reduced to below 1W by 2010. Ministry of Knowledge Economy (MKE, Korean government) and Korea Energy Management Corporation (KEMCO) established &apos;&apos;Standby Korea 2010&apos;&apos; which is a roadmap to limit standby power below 1W by 2010. Korea implemented mandatory program over a relatively short period of time, incorporating the better elements from the more established national program and adding new initiatives, such as the threat of using mandatory warning label for products that fail to meet standby power targets.

  3. Korea&apos;s 1-watt plan &apos;&apos;Standby Korea 2010&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yungrae


    Korea announced standby power of all electronics shall be reduced to below 1W by 2010. Ministry of Knowledge Economy (MKE, Korean government) and Korea Energy Management Corporation (KEMCO) established &apos;&apos;Standby Korea 2010&apos;&apos; which is a roadmap to limit standby power below 1W by 2010. Korea implemented mandatory program over a relatively short period of time, incorporating the better elements from the more established national program and adding new initiatives, such as the threat of using mandatory warning label for products that fail to meet standby power targets.

  4. An integrated evaluation of formation inhomogeneity, accounting for the field &apos;'trend'&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Sultanov, C.A.; Akhmodov, A.M.; Allakhverdieva, L.I.


    It is recommended that the degree of characteristic variation in the geological parameters by area be accounted for using the &apos;'trend'&apos; characteristic when evaluating the geological inhomogeneity of formations; this characteristic denotes any systematic variations which are noted in the diagram of the target under study. A method for solving these problems is proposed. A problem is solved using a sample study of the ruggedness factor of several beds in the 16th formation and the series of the 15th formation in the Starii field and the Bukhti Ilch field in Bibi-Eibat. The &apos;&apos;regression analysis&apos;&apos; program was used in drafting these models; this program was developed at the computer center of the Academy of Sciences of the Estonian SSR. A multiple correlation coefficient for square-law models was used to evaluate the &apos;'trend'&apos;.

  5. Software in the DOE: The Hidden Overhead of&apos;&apos;The Build&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Kumfert, G; Epperly, T


    &apos;&apos;The Build&apos;&apos; is the infrastructure needed to convert software from source code to usable form. It is intimately tied to the software it supports, knowing about every file and automating every transformation needed to produce a working program. Every developer knows that a project spends some labor overhead on &apos;&apos;the build.&apos;&apos; How big is this hidden overhead? According to 34 scientific software developers we surveyed at Lawrence Livermore National Labs, among colleagues at other DOE labs, and a handful of academics the &apos;'perceived'&apos; overhead averages around 12%. Individual cases of 20% to 30% were not uncommon. In one project claiming a 20% overhead, we found supporting evidence by combing through their CVS repository.

  6. Biological effect and tumor risk of diagnostic x-rays. The &apos;&apos;war of the theories&apos;&apos;; Biologische Wirkung und Tumorrisiko diagnostischer Roentgenstrahlen. Der &apos;&apos;Krieg der Modelle&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Selzer, E.; Hebar, A. [Medizinische Universitaet Wien, Abteilung fuer Strahlenbiologie, Klinik fuer Strahlentherapie, Wien (Austria)


    Since the introduction of ionizing radiation as a treatment and diagnostic tool in humans, scientists have been trying to estimate its side effects and potential health risks. There is now ample evidence for the principal existence of a direct relationship between higher doses and the risks of side effects. Most of the uncertainties lie in the field of low-dose effects especially with respect to the risk of cancer induction. Low-dose effects are usually of relevance in diagnostic medicine while high-dose radiation effects are typically observed after radiotherapeutic treatment for cancer or after nuclear accidents. The current state of the &apos;&apos;war of theories&apos;&apos; may be summarized as follows: one group of scientists and health regulatory officials favors the hypothesis that there is no threshold dose, i.e. the linear-no-threshold hypothesis (LNT) of radiation which can be regarded as safe. On the contrary, the critics of this hypothesis suggest that the risks of doses below 50 mSv are not measurable or even of clinical relevance and are not adequately described by a linear dose-response relationship. The aim of this article is to summarize the major unresolved issues in this field. Arguments are presented why the validity of the LNT model in the low-dose range should be regarded as at least inconsistent and is thus questionable. (orig.) [German] Seit der Einfuehrung ionisierender Strahlen als ein Mittel zur Behandlung und Diagnose beim Menschen haben Wissenschaftler versucht, ihre Nebenwirkungen und potenziellen Risiken fuer die Gesundheit einzuschaetzen. Es gibt nun ausreichende Evidenz fuer das grundsaetzliche Vorliegen einer direkten Beziehung zwischen hoeheren Dosen und Nebenwirkungsrisiken. Die meisten Unsicherheiten liegen auf dem Gebiet der Niedrigdosisforschung v. a. im Hinblick auf das Risiko der Induktion von Krebs. Niedrigdosiseffekte sind ueblicherweise von Bedeutung in der diagnostischen Medizin, waehrend Hochdosisbestrahlungseffekte

  7. The concentration of apolipoprotein A-I decreases during experimentally induced acute-phase processes in pigs

    DEFF Research Database (Denmark)

    Carpintero, R.; Pineiro, M.; Andres, M.


    In this work, apolipoprotein A-I (ApoA-I) was purified from pig sera. The responses of this protein after sterile inflammation and in animals infected with Actinobacillus pleuropneumoniae or Streptococcus suis were investigated. Decreases in the concentrations of ApoA-I, two to five times lower...


    Energy Technology Data Exchange (ETDEWEB)

    Rashkov, Valery; Pillepich, Annalisa; Deason, Alis J.; Madau, Piero [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Rockosi, Constance M. [Department of Astronomy and Astrophysics, UCO/Lock Observatory, University of California, Santa Cruz, CA 95064 (United States); Guedes, Javiera [Institute for Astronomy, ETH Zurich, 8093 Zurich (Switzerland); Mayer, Lucio [Institute of Theoretical Physics, University of Zurich, CH-9057 Zurich (Switzerland)


    We discuss a novel approach to &apos;'weighing'&apos; the Milky Way (MW) dark matter halo, one that combines the latest samples of halo stars selected from the Sloan Digital Sky Survey (SDSS) with state of the art numerical simulations of MW analogs. The fully cosmological runs employed in the present study include &apos;'Eris'&apos;, one of the highest resolution hydrodynamical simulations of the formation of a M{sub vir} = 8 Multiplication-Sign 10{sup 11} M{sub Sun} late-type spiral, and the dark-matter-only M{sub vir} = 1.7 Multiplication-Sign 10{sup 12} M{sub Sun} &apos;&apos;Via Lactea II&apos;&apos; (VLII) simulation. Eris provides an excellent laboratory for creating mock SDSS samples of tracer halo stars, and we successfully compare their density, velocity anisotropy, and radial velocity dispersion profiles with the observational data. Most mock SDSS realizations show the same &apos;&apos;cold veil&apos;&apos; recently observed in the distant stellar halo of the MW, with tracers as cold as {sigma}{sub los} Almost-Equal-To 50 km s{sup -1} between 100 and 150 kpc. Controlled experiments based on the integration of the spherical Jeans equation as well as a particle tagging technique applied to VLII show that a &apos;'heavy'&apos; M{sub vir} Almost-Equal-To 2 Multiplication-Sign 10{sup 12} M{sub Sun} realistic host produces a poor fit to the kinematic SDSS data. We argue that these results offer added evidence for a &apos;'light'&apos;, centrally concentrated MW halo.

  9. Feasibility study of the non-invasive estimation of the {beta}{sup +} arterial input function for human PET imaging; Etude de faisabilite de l&apos;estimation non-invasive de la fonction d&apos;entree arterielle {beta}{sup +} pour l&apos;imagerie TEP chez l&apos;homme

    Energy Technology Data Exchange (ETDEWEB)

    Hubert, X.


    This work deals with the estimation of the concentration of molecules in arterial blood which are labelled with positron-emitting radioelements. This concentration is called &apos;{beta}{sup +} arterial input function&apos;. This concentration has to be estimated for a large number of pharmacokinetic analyses. Nowadays it is measured through series of arterial sampling, which is an accurate method but requiring a stringent protocol. Complications might occur during arterial blood sampling because this method is invasive (hematomas, nosocomial infections). The objective of this work is to overcome this risk through a non-invasive estimation of {beta}{sup +} input function with an external detector and a collimator. This allows the reconstruction of blood vessels and thus the discrimination of arterial signal from signals in other tissues. Collimators in medical imaging are not adapted to estimate {beta}{sup +} input function because their sensitivity is very low. During this work, they are replaced by coded-aperture collimators, originally developed for astronomy. New methods where coded apertures are used with statistical reconstruction algorithms are presented. Techniques for analytical ray-tracing and for the acceleration of reconstructions are proposed. A new method which decomposes reconstructions on temporal sets and on spatial sets is also developed to efficiently estimate arterial input function from series of temporal acquisitions. This work demonstrates that the trade-off between sensitivity and spatial resolution in PET can be improved thanks to coded aperture collimators and statistical reconstruction algorithm; it also provides new tools to implement such improvements. (author)

  10. Expression of Fas (CD95/APO-1) ligand by human breast cancers: significance for tumor immune privilege.

    LENUS (Irish Health Repository)

    O'Connell, J


    Breast cancers have been shown to elicit tumor-specific immune responses. As in other types of cancer, the antitumor immune response fails to contain breast tumor growth, and a reduction in both the quantity and cytotoxic effectiveness of tumor-infiltrating lymphocytes (TILs) is associated with a poorer prognosis. Fas ligand (FasL) induces apoptotic death of activated lymphocytes that express its cell surface receptor, FasR (CD95\\/APO-1). FasL-mediated apoptosis of activated lymphocytes contributes to normal immune downregulation through its roles in tolerance acquisition, immune response termination, and maintenance of immune privilege in the eye, testis, and fetus. In this report, we demonstrate that breast carcinomas express FasL. Using in situ hybridization and immunohistochemistry, we show that breast tumors constitutively express FasL at both the mRNA and protein levels, respectively. FasL expression is prevalent in breast cancer: 100% of breast tumors (17 of 17) were found to express FasL, and expression occurred over more than 50% of the tumor area in all cases. By immunohistochemistry, FasR was found to be coexpressed with FasL throughout large areas of all the breast tumors. This suggests that the tumor cells had acquired intracellular defects in FasL-mediated apoptotic signaling. FasL and FasR expression were independent of tumor type or infiltrative capacity. FasL expressed by tumor cells has previously been shown to kill Fas-sensitive lymphoid cells in vitro and has been associated with apoptosis of TILs in vivo. We conclude that mammary carcinomas express FasL in vivo as a potential inhibitor of the antitumor immune response.

  11. In vitro binding of plutonium to human transferrin and competition reaction with ferric ions; Fixation in vitro du plutonium sur la siderophiline humaine et reaction de competition avec l&apos;ion ferrique

    Energy Technology Data Exchange (ETDEWEB)

    Massey, P.; Lafuma, J. [Commissariat a l' Energie Atomique, 92 - Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires


    Plutonium was found to bind strongly to human transferrin, however a maximum capacity of absorption was observed. Presaturation with iron of transferrin resulted in a decrease of plutonium binding, but it still remained appreciable. It was largely affected by the pH as well as by the degree of ferric saturation of the transferrin. (authors) [French] Le plutonium se fixe solidement sur la siderophiline humaine, toutefois on assiste a une capacite d&apos;absorption limite. Une presaturation par le fer de la siderophiline, diminue l&apos;attraction du plutonium, cependant celle-ci reste importante. L&apos;influence du pH est tres importante ainsi que les degres de saturation ferrique de la siderophiline. (auteurs)

  12. Structures of human Bruton&apos;s tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases

    Energy Technology Data Exchange (ETDEWEB)

    Marcotte, Douglas J.; Liu, Yu-Ting; Arduini, Robert M.; Hession, Catherine A.; Miatkowski, Konrad; Wildes, Craig P.; Cullen, Patrick F.; Hong, Victor; Hopkins, Brian T.; Mertsching, Elisabeth; Jenkins, Tracy J.; Romanowski, Michael J.; Baker, Darren P.; Silvian, Laura F. (Sunesis); (Biogen)


    Bruton&apos;s tyrosine kinase (BTK), a member of the TEC family of kinases, plays a crucial role in B-cell maturation and mast cell activation. Although the structures of the unphosphorylated mouse BTK kinase domain and the unphosphorylated and phosphorylated kinase domains of human ITK are known, understanding the kinase selectivity profiles of BTK inhibitors has been hampered by the lack of availability of a high resolution, ligand-bound BTK structure. Here, we report the crystal structures of the human BTK kinase domain bound to either Dasatinib (BMS-354825) at 1.9 {angstrom} resolution or to 4-amino-5-(4-phenoxyphenyl)-7H-pyrrolospyrimidin- 7-yl-cyclopentane at 1.6 {angstrom} resolution. This data provides information relevant to the development of small molecule inhibitors targeting BTK and the TEC family of nonreceptor tyrosine kinases. Analysis of the structural differences between the TEC and Src families of kinases near the Trp-Glu-Ile motif in the N-terminal region of the kinase domain suggests a mechanism of regulation of the TEC family members.

  13. The Legionella &apos;'killer'&apos; was right: Hot water increases safety; Legionella-&apos;'doedaren'&apos; fikk rett: varmt vann oeker sikkerheten

    Energy Technology Data Exchange (ETDEWEB)

    Brekke, Ragnar


    In Norway the last years there have been some outbreaks of the Legionnaires&apos; Disease. This has taken many by surprise, although in the 1990s the water heater manufacturer referred to in this article had warned against it. The heater temperature should not be subject to energy conservation experiments. &apos;'Legionnaires&apos; Desease&apos;&apos; and &apos;&apos;Pontiac Fever&apos;&apos; are caused by bacteria from the Legionella family. Legionnaires&apos; Disease is a kind of pneumonia and Pontiac Fever is an influenza-like illness. The Legionella bacteria spread via small water particles (aerosols) in the air from showers, whirl pools, cooling towers etc. The bacteria thrive in stagnant water in the temperature range 20 - 45 {sup o}C, where they can multiply to dangerous concentrations. In water heaters that have low temperatures around 40 {sup o}C, populations of Legionella bacteria can grow to become a problem. The article recommends that the heater temperature should be kept at 75{sup o}C.

  14. Biokinetic of plutonium in human beings. Analysis and modification of ICRP 67 model; Biocinetica del plutonio nell&apos;organismo umano. Analisi e modifica del modello ICRP 67

    Energy Technology Data Exchange (ETDEWEB)

    Luciani, A.; Castellani, C.M. [ENEA, Divisione Protezione dell' Uomo e degli Ecosistemi, Centro Ricerche Ezio Clementel, Bologna (Italy)


    A preliminary research of the available data and empirical functions for the plutonium excretion after injection was carried out. The ICRP model presented in the Publication no. 67 was then analyzed comparing its predictions for the activity in urine and, at a lesser extent, in feces and blood, with the collected data and empirical curves. The model was modified and an optimized age-related compartmental model was developed. A new skeletal model recently developed was also introduced and age depending bone remodelling rates were assumed on the basis of the ICRP Publication 70. This model provides a better agreement with measured urinary excretion data than the current ICRP 67 model, avoiding unphysiological assumptions such as the transfer of activity from soft tissue to urinary bladder, that were part of the ICRP model. The new optimized model predictions of the activity in faeces and in blood after an injection are also closer to the available data than the ICRP 67 estimations. A good agreement with the partitioning factor of plutonium between skeleton and liver obtained from different autopsy studies was also observed. [Italian] E&apos; stata effettuata preliminarmente una ricerca bibliografica dei dati e delle funzioni di escrezione del plutonio attualmente disponibili in letteratura. Sulla base dei risultati di tale ricerca e&apos; stato verificato il modello proposto dall&apos;ICRP nella Pubblicazione n. 67. Tale modello e&apos; stato quindi modificato al fine non solo di avere una piu&apos; realistica descrizione dei valori predetti per l&apos;escrezione urinaria, ma anche di modellare la cinetica del plutonio evitando quelle assunzioni introdotte appositamente nel modello dell&apos;ICRP per correggere le previsini del modello ma che mancano di una chiara spiegazione di carattere fisiologico. Esso fornisce valutazioni piu&apos; realistiche anche per l&apos;attivita&apos; nelle feci e nel sangue. Il modello sviluppato comprende un modello scheletrico

  15. Apolipoprotein A-I mutant proteins having cysteine substitutions and polynucleotides encoding same (United States)

    Oda, Michael N.; Forte, Trudy M.


    Functional Apolipoprotein A-I mutant proteins, having one or more cysteine substitutions and polynucleotides encoding same, can be used to modulate paraoxonase's arylesterase activity. These ApoA-I mutant proteins can be used as therapeutic agents to combat cardiovascular disease, atherosclerosis, acute phase response and other inflammatory related diseases. The invention also includes modifications and optimizations of the ApoA-I nucleotide sequence for purposes of increasing protein expression and optimization.

  16. Effects of lovastatin on ApoA- and ApoB-containing lipoproteins. Families in a subpopulation of patients participating in the Monitored Atherosclerosis Regression Study (MARS). (United States)

    Alaupovic, P; Hodis, H N; Knight-Gibson, C; Mack, W J; LaBree, L; Cashin-Hemphill, L; Corder, C N; Kramsch, D M; Blankenhorn, D H


    To establish whether lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, exhibits a specific effect on apolipoprotein (apo) A- and apoB-containing lipoproteins, 63 subjects, a subset of the 270 Monitored Atherosclerosis Regression Study (MARS) patients with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease, were randomized into either lovastatin 40 mg twice daily or matching placebo tablets twice daily. Both groups consumed a diet containing 27% calories as fat (polyunsaturated fat/saturated fat ratio, 2.85) and a daily cholesterol intake of less than 250 mg. The plasma lipid and apolipoprotein profiles were determined at the time of randomization and after 2 years of treatment, and the levels of apoA- and apoB-containing lipoprotein families were measured after 2 years of treatment. After this treatment period, the drug group was characterized in comparison with the placebo group by significantly reduced levels of total cholesterol (33%), triglycerides (30%), very-low-density lipoprotein cholesterol (36%), low-density lipoprotein cholesterol (43%), apoB (36%), apoC-III (18%), and apoE (17%) and slightly but insignificantly increased levels of high-density lipoprotein cholesterol (6%) and apoA-I (1%). The 2-year levels of lipoprotein containing apoA-I but no apoA-II (LpA-I) and lipoprotein containing both apoA-I and apoA-II (LpA-I/A-II) particles separated by immunoaffinity chromatography on an anti-apoA-II immunosorber did not differ between the two treatment groups. However, the apoB-containing lipoprotein (Lp) families defined by apolipoprotein composition and separated by immunoaffinity chromatography on anti-apoA-II and anti-apoC-III immunosorbers were affected in a selective manner.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Maturation of secreted HCV particles by incorporation of secreted ApoE protects from antibodies by enhancing infectivity. (United States)

    Bankwitz, Dorothea; Doepke, Mandy; Hueging, Kathrin; Weller, Romy; Bruening, Janina; Behrendt, Patrick; Lee, Ji-Young; Vondran, Florian W R; Manns, Michael P; Bartenschlager, Ralf; Pietschmann, Thomas


    Hepatitis C virus (HCV) evades humoral immunity and establishes chronic infections. Virus particles circulate in complex with lipoproteins facilitating antibody escape. Apolipoprotein E (ApoE) is essential for intracellular HCV assembly and for HCV cell entry. We aimed to explore if ApoE released from non-infected cells interacts with and modulates secreted HCV particles. ApoE secreted from non-infected cells was incubated with HCV from primary human hepatocytes or Huh-7.5 cells. Co-immunoprecipitation, viral infectivity and neutralization experiments were conducted. Physiological levels of secreted ApoE (10-60µg/ml) enhanced the infectivity of HCV up to 8-fold across all genotypes, which indirectly decreased virus neutralization by antibodies targeting E1 or E2 up to 10-fold. Infection enhancement was observed for particles produced in primary human hepatocytes and Huh-7.5 cells. Selective depletion of ApoE ablated infection enhancement. Addition of HA-tagged ApoE to HCV particles permitted co-precipitation of HCV virions. Serum ApoE levels ranged between 10-60µg/ml, which is ca 100-fold higher than in Huh-7.5 conditioned cell culture fluids. Serum-derived HCV particles carried much higher amounts of ApoE than cell culture-derived HCV particles. Serum ApoE levels correlated with efficiency of co-precipitation of HCV upon exogenous addition of HA-ApoE. ApoE-dependent infection enhancement was independent of the hypervariable region 1 and SR-B1, but was dependent on heparan sulfate proteoglycans (HSPGs). Physiological quantities of secreted ApoE stimulate HCV infection and increase antibody escape, by incorporating into virus particles and enhancing particle interactions with cellular HSPGs. Thus, secreted particles undergo ApoE-dependent maturation to enhance infectivity and to facilitate evasion from neutralizing antibodies. Lay summary: This study shows that HCV particle infectivity is remodeled by secreted ApoE after particle release from cells. Fluctuation of

  18. Identification of a novel enhancer of brain expression near the apoE gene cluster by comparative genomics

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Ping; Pennacchio, Len A.; Goff, Wilfried Le; Rubin, Edward M.; Smith, Jonathan D.


    Comparative analysis of the human and mouse genomic sequences downstream of the apolipoprotein E gene (APOE) revealed a highly conserved element with previously undefined function. In reporter gene transfection studies, this element which is located f42 kb distal to APOE was found to have silencer activity in a subset of cell lines examined. Analysis of transgenic mice containing a fusion construct linking this distal 631 bp conserved element to a reporter gene comprised of the human APOE gene with its proximal promoter resulted in robust brain expression of the transgenic human apoE mRNA in three independent transgenic lines, supporting the identification of a novel brain controlling region (BCR). Further studies using immunohistochemistry revealed widespread human apoE localization throughout the brains of the BCR-apoE transgenic mice with prominent expression in the cortex and diencephalon. In addition, double-label immunofluorescence performed on brain sections and cultures of primary cortical cells localized human apoE protein to cortical neurons and microglia. These studies demonstrate that comparative sequence analysis is a successful strategy to predict candidate regulatory regions in vivo, although they do not imply that this element controls apoE expression physiologically.

  19. Augmented atherogenesis in LDL receptor deficient mice lacking both macrophage ABCA1 and ApoE.

    Directory of Open Access Journals (Sweden)

    Bart Lammers

    Full Text Available AIM: ABCA1 protects against atherosclerosis by facilitating cholesterol efflux from macrophage foam cells in the arterial wall to extracellular apolipoprotein (apo A-I. In contrast to apoA-I, apoE is secreted by macrophages and can, like apoA-I, induce ABCA1-mediated cholesterol efflux. Yet, the combined effect of macrophage ABCA1 and apoE on lesion development is unexplored. METHODS AND RESULTS: LDL receptor knockout (KO mice were transplanted with bone marrow from ABCA1/apoE double KO (dKO mice, their respective single KO's, and wild-type (WT controls and were challenged with a high-fat/high-cholesterol diet for 9 weeks. In vitro cholesterol efflux experiments showed no differences between ABCA1 KO and dKO macrophages. The serum non-HDL/HDL ratio in dKO transplanted mice was 1.7-fold and 2.4-fold (p<0.01 increased compared to WT and ABCA1 KO transplanted mice, respectively. The atherosclerotic lesion area in dKO transplanted animals (650±94×10(3 µm(2, however, was 1.9-fold (p<0.01 and 1.6-fold (p<0.01 increased compared to single knockouts (ABCA1 KO: 341±20×10(3 µm(2; apoE KO: 402±78×10(3 µm(2, respectively and 3.1-fold increased (p<0.001 compared to WT (211±20×10(3 µm(2. When normalized for serum cholesterol exposure, macrophage ABCA1 and apoE independently protected against atherosclerotic lesion development (p<0.001. Moreover, hepatic expression levels of TNFα and IL-6 were highly induced in dKO transplanted animals (3.0-fold; p<0.05, and 4.3-fold; p<0.001, respectively. In agreement, serum IL-6 levels were also enhanced in ABCA1 KO transplanted mice (p<0.05 and even further enhanced in dKO transplanted animals (3.1-fold as compared to ABCA1 KO transplanted animals; p<0.05. CONCLUSIONS: Combined deletion of macrophage ABCA1 and apoE results in a defect in cholesterol efflux and, compared to ABCA1 KO transplanted mice, elevated serum total cholesterol levels. Importantly, these mice also suffer from enhanced systemic and hepatic

  20. [18F]FLT and [18F]FDG PET for non-invasive treatment monitoring of the nicotinamide phosphoribosyltransferase inhibitor APO866 in human xenografts

    DEFF Research Database (Denmark)

    Erichsen, Kamille Dumong; Johnbeck, Camilla Bardram; Björkling, Fredrik


    APO866 is a new anti-tumor compound inhibiting nicotinamide phosphoribosyltransferase (NAMPT). APO866 has an anti-tumor effect in several pre-clinical tumor models and is currently in several clinical phase II studies. 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) is a tracer used to assess cell...

  1. Effect of Body Mass Index on Apolipoprotein A-I Kinetics in Middle-Aged Men and Postmenopausal Women (United States)

    Welty, Francine K.; Lichtenstein, Alice H.; Lamon-Fava, Stefania; Schaefer, Ernst J.; Marsh, Julian B.


    The effect of body mass index (BMI) and obesity on apo A-I levels and kinetics was examined by gender. ApoA-I kinetics were determined with a primed-constant infusion of deuterated leucine in the fed state in 19 men and 13 postmenopausal women. Compared to nonobese men, nonobese women had a higher HDL-C and apoA-I level due to a 48% higher apoA-I PR (p=0.05). Obesity had no significant effects on apoA-I kinetics in women. In contrast, compared to non-obese men, obese men had a 9% lower apoA-I level due to a 64% higher FCR partially offset by a 47% higher PR. Obese women had a 52% higher HDL-C than obese men (50 mg/dL vs 33 mg/dL, respectively, p=0.012), a finding related to the faster apoA-I FCR in obese men. BMI was directly correlated with apoA-1 FCR (r = 0.84, p < 0.001) and PR (r = 0.79, p < 0.001) in men but not women. 62% of the variability in PR and 71% of the variability in FCR were due to BMI in men and only 3% and 23%, respectively, in women. In conclusion, BMI has a significant effect on apoA-I PR and FCR in men but not in women. PMID:17570251

  2. The &apos;'passivhaus'&apos; standard: from energy efficiency to &apos;green&apos; building; Le standard &apos;'passivhaus'&apos;: de la performance energetique a la construction &apos;'verte'&apos;

    Energy Technology Data Exchange (ETDEWEB)



    The German voluntary standard &apos;Passivhaus&apos; (passive house) leads to buildings with practically no energy consumption. The first residential buildings of this type were built in 1998 and the first tertiary buildings in 2000. Such a passive house must fulfill 5 efficiency criteria: annual space heating needs {<=} 15 kWh/m{sup 2}, U{sub v} envelope coefficient lower than 0.15 W/(m{sup 2}.K), U{sub v} of openings lower than 0.8 W/(m{sup 2}.K), airtightness {<=} 0.6 volume/hour, and total energy needs (space heating, hot water, ventilation, lighting and domestic uses) measured at the meter lower than 42 kWh/m{sup 2}.year. This article makes a status of the effective efficiency of existing passive buildings both in the residential and tertiary sectors and presents some possible ways of improvement. (J.S.)

  3. &apos;&apos;Social capitalism&apos;&apos; in renewable energy generation: China and California comparisons

    Energy Technology Data Exchange (ETDEWEB)

    Clark, Woodrow W. II.; Li, Xing [Clark Strategic Partners, PO Box 17975, Beverly Hills, CA 90210 (United States)


    With a population of over 1.3 billion people, demand for renewable energy is expected to grow to a USD $12 billion market in the near term. Under Renewable Energy Law (REL) in February 2005 in the People&apos;s Republic of China (PRC) passed by the National Congress, renewable energy projects will be able to receive a range of financial incentives starting in 2006, which will more than double the PRC current renewable energy generation from 7% to 15% by 2020. Most of the increase will be in hydroelectric generated power. Nonetheless, the nation and especially the provinces are moving rapidly to develop a wide range of renewable energy generation including solar, wind, geothermal and run of the river. Because China practices &apos;&apos;social capitalism&apos;&apos; as expressed in it&apos;s recurrent Five Year National Plans since 1999, the national government and all the provinces have programs, unlike many western and industrialized nations, to &apos;'plan'&apos; and provide for infrastructures. This paper concerns only the energy infrastructure sector and renewable energy generation in particular. The planning process includes financial incentives and investments which are a major part of the Chinese law focused on &apos;&apos;encouraging foreign investment industries&apos;&apos;. The key part of the law is to guarantee long-term power purchase agreements with state owned and controlled &apos;'utilities'&apos;. In short, China may have gotten the economics of the energy sector correct in its concern for planning and finance. The paper develops these energy infrastructure ideas along with the legal and financial requirements as &apos;'lessons'&apos; learned from the USA and especially California. These lessons now apply to China and allow it to learn from the American mistakes. Empirical data will be drawn from work done in China that examine the renewable energy generation and infrastructures and hence allow the RPC and its

  4. Reflection group on &apos;Expert Culture&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Eggermont, G


    As part of SCK-CEN&apos;s social sciences and humanities programme, a reflection group on &apos;Expert Culture&apos; was established. The objectives of the reflection group are: (1) to clarify the role of SCK-CEN experts; (2) to clarify the new role of expertise in the evolving context of risk society; (3) to confront external views and internal SCK-CEN experiences on expert culture; (4) to improve trust building of experts and credibility of SCK-CEN as a nuclear actor in society; (5) to develop a draft for a deontological code; (6) to integrate the approach in training on assertivity and communication; (7) to create an output for a topical day on the subject of expert culture. The programme, achievements and perspectives of the refection group are summarised.

  5. Mencius&apos; Educational Philosophy and Its Contemporary Relevance (United States)

    Huang, Chun-chieh


    This article argues that Mencius&apos; education is "holistic education" that aims at igniting the "silent revolution" from within one&apos;s inner mind-heart to be unfolded in society, state, and the world. Mencius&apos; educational philosophy is based on his theory of human nature and his theory of self-cultivation. Mencius…

  6. Report of working committee 4 &apos;&apos;transmission of gases&apos;&apos;; Rapport de la commission 4 &apos;&apos;transport des gaz&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Volskij, E.


    Report of the WOC 4 Transmission contains the results of works carried out during 1998-2000 by the Committee members and the three study groups. The most important is: - review of actual situation and prospects for the gas pipeline transmission system development; - report of SG-4.1 &apos;Pipeline Ageing and Rehabilitation&apos;, including analysis of pipeline steels, welding and insulation, methods of rehabilitation, the program of pipeline reconstruction; - report of SG-4.2 &apos;Emission monitoring&apos; including appraisal of gas losses and methods of lowering of methane and other emissions of the gas units in different countries; - report of SG-4.3 &apos;Pipelines Integrity Management and Safety&apos; including basic information on gas pipeline failure intensity, key elements of the Integrity Management System of the gas transmission, methods of risk evaluation and the effectiveness of the approach. (authors)

  7. Utilization of demolished composition materials of &apos;'ClimateHouses'&apos;; Verwertung des Abbruchmaterials von &apos;'KlimaHaeusern'&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Knappe, Florian; Diebel, Anton; Reinhardt, Joachim; Theis, Stefanie [ifeu-Institut fuer Energie- und Umweltforschung GmbH, Heidelberg (Germany); Leiter, Elisabeth; Rosanelli, Rupert; Vieider, Andreas [Syneco, Bolzano (Italy); Feess, Walter [Firma Feess Erdbau, Kirchheim/Teck (Germany); Bonadio, Martina


    In the year 1992, an innovative concept of energy conservation was developed in order to improve the energy standards of new buildings as well as existing buildings. The model &apos;ClimateHouse&apos; has to reduce significantly the energy demand in the area of needs building and living as well as the use of fossil resources and negative impacts on the climate. First of all the authors of the contribution under consideration report on and balance the situation in the province South Tyrol with respect to the design of &apos;ClimateHouses&apos; and the use of construction materials for &apos;ClimateHouses&apos;. This also is valid for solar panels. Within a second step the authors report on how the waste management has to be arranged to other waste mass flows and waste compositions.

  8. Open refrigerating display case &apos;MAX series&apos; for supermarkets; Supermarket muke denki reizo open showcase (MAX series)

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, E.; Sudo, H.; Aoyama, Y. [Fuji Electric Co. Ltd., Tokyo (Japan)


    Fuji Electric has developed the open refrigerating display case &apos;MAX Series&apos; for supermarkets which has further pursued &apos;articles easy to see, select, and take out&apos; on the concept of &apos;friendliness&apos; as well as friendliness to customers and installation workers. Its main advantages are (1) The dimensions were determined based on human engineering and improved the display effect of articles. This enables the exhibits to strongly appeal to customers. (2) The air curtain optimized through simulation realizes uniform temperature in the case, reduction in energy consumption, and high freshness control. (author)

  9. Effects of modern and ancient human activities on mercury in the environment in Xi&apos;an area, Shannxi Province, P.R. China

    Energy Technology Data Exchange (ETDEWEB)

    Jin Yongqing; Wang Xiaojuan [Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Materials Science, Shaanxi Normal University, Xi' an 710062 (China); Department of Chemistry and Biology, Ryerson University, 350 Victoria Street, Toronto, ON, M5B 2K3 (Canada); Lu Julia [Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Materials Science, Shaanxi Normal University, Xi' an 710062 (China); Department of Chemistry and Biology, Ryerson University, 350 Victoria Street, Toronto, ON, M5B 2K3 (Canada)], E-mail:; Zhang Chengxiao [Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Materials Science, Shaanxi Normal University, Xi' an 710062 (China)], E-mail:; Duan Qingbo [Shaanxi Archaeology Institute, Xi' an 710054 (China)


    Samples of water, soil, sediment, and pomegranate were collected from Xi&apos;an and the Qinshihuang Mausoleum in Shaanxi Province, China to assess the effects of human activities on mercury in the environment. The total mercury concentrations ranged from 3.9 to 992.7 ng L{sup -1} for the water samples, 40.6 to 2204.0 ng g{sup -1} for the soil samples, 14.2 to 376.7 ng g{sup -1} for the sediment samples, and 0.22 to 1.74 ng g{sup -1} for the pomegranates samples. The higher values in the water samples collected from the rivers closer to and downstream of the city resulted from wastewater discharges. The effects of the mercury buried in the Qinshihuang Mausoleum thousands of years ago on the environment were neither significant nor widespread. Immediate actions should be taken to stop the direct and continuous discharges of industrial and residential wastewaters to prevent mercury and other pollutants from accumulating and spreading in the area. - Urban activities are sources of mercury to the environment and the pomegranates grown over the burial mound of the Qinshihuang Mausoleum are not mercury-contaminated.

  10. 3&apos;,8&apos;&apos;-biisokaempferide, a cytotoxic biflavonoid and other chemical constituents of Nanuza plicata (Velloziaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Meri Emili F.; Silva, Marcelo Sobral da; Barbosa Filho, Jose Maria; Castello-Branco, Marianna Vieira S.; Agra, Maria de Fatima; Tavares, Josean Fechine, E-mail: marcelosobral@ltf.ufpb.b [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Lab. de Tecnologia Farmaceutica; Schindler, Elisabete; El-Bacha, Ramon dos Santos [Universidade Federal da Bahia (UFBA), Salvador, BA (Brazil). Inst. de Ciencias da Saude. Lab. de Neuroquimica e Biologia Celular


    A novel biflavonoid, named 3&apos;,8&apos;&apos;-biisokaempferide (1), along with the known compounds amentoflavone (2), patagonic acid (3), (4aR,5S,6R,8aR)-5-[2-(2,5-Dihydro-5-methoxy-2-oxofuran- 3-yl)ethyl]-3,4,4a,5,6,7,8,8a-octahydro-5,6,8a- trimethylnaphthalene-1-carboxylic acid (4), 5-caffeoylquinic acid methyl ester (5), 3,5-di-caffeoylquinic acid (6) and luteolin (7), were isolated of the leaves from Nanuza plicata. The compounds 3, 4, 5 and 6 are reported for the first time in Velloziaceae. The structures of the compounds were elucidated on the basis of spectroscopic methods, especially NMR and MS analyses. The cytotoxicity of 3&apos;,8&apos;&apos;-biisokaempferide was studied in cultures of human glioblastoma GL-15 cells. The effective concentration, which killed 50 % of cells after 72 h was 36.5 {mu}mol L{sup -1}. Changes in cellular morphology, including retraction and degradation of cytoplasm, were observed when cells were treated with concentrations from 20 {mu}mol L-1 of 3&apos;,8&apos;&apos;-biisokaempferide for 72 h. (author)

  11. &apos;&apos;Substantial Margin of Safety&apos;&apos;: A New Approach to HLW Disposition

    Energy Technology Data Exchange (ETDEWEB)

    Power, M. S.


    In the Spring of 2001, the National Research Council published &apos;&apos;Disposition of High-Level Waste and Spent Nuclear Fuel: The Continuing Societal and Technical Challenges.&apos;&apos; (1) While finding the technical case for deep geologic disposal of high-level waste and spent fuel robust, the report focused new attention on societal issues and decision-making. The report appeared against a backdrop of heightened controversy about the development of a geologic repository at Yucca Mountain, Nevada. This paper identifies three principal reasons for the National Research Council committee&apos;s finding that &apos;&apos;Difficulties in achieving public support have been seriously underestimated in the past, and opportunities to gain public trust have been missed.&apos;&apos;

  12. Energy and the new class. [Assault of &apos;&apos;new breed&apos;&apos; of American on established institutions

    Energy Technology Data Exchange (ETDEWEB)

    King, L.


    The bounty of the US is taken for granted by its population. Nowhere is this misvaluation of a society and its benefits more evident than in the energy industries. But energy represents a tool by which society can be shaped; a device by which the standared of living and the very nature of the national lifestyle can be controlled, modified, amplified, or reduced. Two examples examined to show how energy shapes social order and human life are the women&apos;s movement and the desire to live in the Sunbelt. Five phenomena are then examined to point out the desire to restrain the nation&apos;s rampant pursuit of a higher standard of living, as opposed to the more subjective and seemingly more desirable goal of a better quality of life: the civil rights movement; the environmental movement; the Vietnam War; the Watergate scandal; and the assumption that prosperity at today&apos;s level is irreducible, concrete, and not subject to diminution. The &apos;&apos;new class&apos;&apos; is essentially made up of those educated in the liberal arts, divorced from an understanding of the mechanics of free-enterprise institutions and of the sicences. The antagonistic view of the new class of corporations and its assault on established institutions are noted. Energy companies are frustrated in telling their story, but the story that must be told is not the story of how excellently the energy sector has performed, but the story of how a new breed of Americans is seeking to remake America in its own image without the rest being aware of what is going on. (MCW)

  13. Expression and purification of recombinant apolipoprotein A-I Zaragoza (L144R) and formation of reconstituted HDL particles. (United States)

    Fiddyment, Sarah; Barceló-Batllori, Sílvia; Pocoví, Miguel; García-Otín, Angel-Luis


    Apolipoprotein A-I Zaragoza (L144R) (apo A-I Z), has been associated with severe hypoalphalipoproteinemia and an enhanced effect of high density lipoprotein (HDL) reverse cholesterol transport. In order to perform further studies with this protein we have optimized an expression and purification method of recombinant wild-type apo A-I and apo A-I Z and produced mimetic HDL particles with each protein. An pET-45 expression system was used to produce N-terminal His-tagged apo A-I, wild-type or mutant, in Escherichia coli BL21 (DE3) which was subsequently purified by affinity chromatography in non-denaturing conditions. HDL particles were generated via a modified sodium cholate method. Expression and purification of both proteins was verified by SDS-PAGE, MALDI-TOF MS and immunochemical procedures. Yield was 30mg of purified protein (94% purity) per liter of culture. The reconstituted HDL particles checked via non-denaturing PAGE showed high homogeneity in their size when reconstituted both with wild-type apo A-I and apo A-I Z. An optimized system for the expression and purification of wild-type apo A-I and apo A-I Z with high yield and purity grade has been achieved, in addition to their use in reconstituted HDL particles, as a basis for further studies.

  14. Perfluorinated carboxylic acids in human breast milk from Spain and estimation of infant&apos;s daily intake

    Energy Technology Data Exchange (ETDEWEB)

    Motas Guzmàn, Miguel [Área de Toxicología, Universidad de Murcia, Campus de Espinardo, 30100 Murcia (Spain); Clementini, Chiara [University of Siena, Department of Physical Sciences, Earth and Environment, Via Mattioli, 4, 53100 Siena (Italy); Pérez-Cárceles, Maria Dolores; Jiménez Rejón, Sandra [Department of Legal Medicine, School of Medicine, University of Murcia & Instituto Murciano de Investigacion Biomedica (IMIB), (IMIB-VIRGEN DE LA ARRIXACA), Murcia (Spain); Cascone, Aurora; Martellini, Tania [Department of Chemistry “Ugo Schiff”, via della Lastruccia 3, 50019 Sesto Fiorentino, Firenze (Italy); Guerranti, Cristiana [University of Siena, Department of Physical Sciences, Earth and Environment, Via Mattioli, 4, 53100 Siena (Italy); Bioscience Research Center, Via Aurelia Vecchia 32, 58015 Orbetello, GR (Italy); Cincinelli, Alessandra, E-mail: [Department of Chemistry “Ugo Schiff”, via della Lastruccia 3, 50019 Sesto Fiorentino, Firenze (Italy)


    Human milk samples were collected from 67 mothers in 2014 at a Primary Care Centre in Murcia (Spain) and analyzed for perfluorinated carboxylic acids (PFCAs). Concentrations measured for perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA) and perfluorododecanoic acid (PFDoDA) ranged from < LOQ (< 10 ng/L) to 397 ng/L with a mean concentration of 66 ± 68 ng/L and a median of 29 ng/L. The presence of these compounds was revealed in 50 samples out of 67 analyzed. Influence of number of pregnancies and food habits on PFCAs concentrations was also investigated. Statistically significant differences in PFCA levels were found when the women were divided into maternal age classes and into the categories primiparae and multiparae. A greater transfer of PFC during breastfeeding by primiparous was evidenced and thus a higher exposure to these contaminants for the first child. Moreover, it was possible to hypothesize that the content of PFCs is in general correlated to the eating habits of donors and, in particular, with the fish consumption. Finally, PFOA daily intakes and risk index (RI) were estimated for the first six months of life and we found that ingestion rates of PFOA did not exceed the tolerable daily intake (TDI) recommended by the European Food Safety Authority (EFSA). - Graphical abstract: Figure SI 1. Concentrations (ng/L) of PFCs recovered in 67 samples of human breast milk. - Highlights: • Perfluorinated carboxylic acids were analyzed in a set of 67 breast milk samples collected from Spanish women. • PFOA appeared as the major contributor to the total perfluorinated carboxylic acids. • PFOA concentrations were significantly higher in milk of primiparous participants. • PFOA daily intake and risk index were estimated for the firsts six month of life.

  15. The &apos;&apos;state of the art in science&apos;&apos; examined as a concept of law from the angle of epistemology, with the example of the principle of averting danger, as defined in the emission control law and in the atomic energy law. Der Rechtsbegriff &apos;&apos;Stand der Wissenschaft&apos;&apos; aus erkenntnistheoretischer Sicht am Beispiel der Gefahrenabwehr im Immissionsschutz- und Atomrecht

    Energy Technology Data Exchange (ETDEWEB)

    Lohse, D.


    The term &apos;&apos;state of the art in science&apos;&apos; is the essential element guaranteeing the legally required measures for averting danger during specified normal operation and in case of an accident, as defined in the Atomic Energy Act and in the Federal Emission Control Act. The literature, jurisdiction, and the licensing practice are not unanimous in the interpretation of the content of this term &apos;&apos;state of the art in science&apos;&apos;, its function in the licensing procedure, and its distinctions as compared to the term &apos;&apos;state of the art in technology&apos;&apos;. The book in hand sets out to provide answers. The term state of the art in science appears at different places in the Atomic Energy Act (AtG) or the Federal Emission Control Act (BImSchG), and in different factual contexts. Reference to the measures for averting danger offers the possibility of gearing to a specific context of this term and thus to discuss the term in a selected context. The principle of averting danger therefore offers the factual frame for an epistemological examination of the term &apos;&apos;state of the art in science&apos;&apos;. Other than the Federal Constitutional Court in its Kalkar reactor judgment, the author&apos;s opinion is that the limits of the human capacity of knowledge are not due to theoretical capacities, but rather to practical. The aquired knowledge thus lags behind the knowledge achievable from the angle of epidemology. The remaining uncertainty in the author&apos;s theory thus is larger than that assumed in the judgment of the Federal Constitutional Court. The limits of the human capacity of knowledge, the author says, cannot be regarded to likewise set the same limits to the principle or instrument of averting danger. The limits of averting danger are a result of the administrative capacities. (orig.)

  16. The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein. (United States)

    Kozyraki, R; Fyfe, J; Kristiansen, M; Gerdes, C; Jacobsen, C; Cui, S; Christensen, E I; Aminoff, M; de la Chapelle, A; Krahe, R; Verroust, P J; Moestrup, S K


    Cubilin is the intestinal receptor for the endocytosis of intrinsic factor-vitamin B12. However, several lines of evidence, including a high expression in kidney and yolk sac, indicate it may have additional functions. We isolated apolipoprotein A-I (apoA-I), the main protein of high-density lipoprotein (HDL), using cubilin affinity chromatography. Surface plasmon resonance analysis demonstrated a high-affinity binding of apoA-I and HDL to cubilin, and cubilin-expressing yolk sac cells showed efficient 125I-HDL endocytosis that could be inhibited by IgG antibodies against apoA-I and cubilin. The physiological relevance of the cubilin-apoA-I interaction was further emphasized by urinary apoA-I loss in some known cases of functional cubilin deficiency. Therefore, cubilin is a receptor in epithelial apoA-I/HDL metabolism.

  17. Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Lundegaard, Christiane; Tybjærg-Hansen, Anne; Grande, Peer


    Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD).......Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD)....

  18. 1982 Resident&apos;s Essay Award: the immunologic effects of lymphoid irradiation in human and non-human primates: cellular changes and the potential for renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Halperin, E.C.; Haas, G.; Dosoretz, D.E.; Gitterman, M.; Barrett, L.; Cosimi, A.B.; Suit, H.D.; Phil, D.


    Previous reports have suggested that the immunosuppressive effects of lymphoid irradiation (LI) are related to changes in T cell peripheral blood levels. We prospectively studied 13 patients with Stages I and II Hodgkin&apos;s disease before, during, and after a course of LI. Forty to 45Gy delivered to the mantle field in 4-1/2 to 5 weeks was followed by a 3 to 4 week break and 35 to 40 Gy to the paraaortic field. The absolute lymphocyte count prior to LI was 1400 +- 270/mm3. This fell to 597 +- 280/mm3 at the conclusion of LI and returned to 1490 +- 800/mm3 at 7 to 8 months post-LI. Seven previously spleenectomized cynomolgus monkeys received 20Gy of LI in 20 equal daily fractions over a 4 week period through a single anterior field including the cervical, axillary, mediastinal, paraaortic, iliac, and inguinal lymph node chains at a dose rate of 4.6 to 4.8cGy/minute. Renal allografts from unrelated monkey donors were placed following LI. Graft function was monitored by urine output, serum BUN and creatinine, and renal biopsy. Low dose rate LI was well tolerated. The absolute lymphocyte count fell from a pre-LI level of 3080 +- 1227/mm3 to 534 +- 478/mm3 at 1 month post-LI. In 4 animals that received no LI (controls), survival post-transplant was 8 to 11 days prior to death from acute rejection. Five animals received transplants immediately following LI. Four survived 11 to 56 days prior to death of presumed infection. One died at day 45 with rejection. Another group of two animals received transplants 3-1/2 weeks after LI. One died of rejection at day 42. One remains well at day 394 post-transplant.

  19. Study of environmental factors&apos; influence on the human health in the case of the Moscow population

    Energy Technology Data Exchange (ETDEWEB)

    Bykov, A. [International Inst. of Risk Research, Moscow (Russian Federation); Pronina, I. [Moscow State Univ. (Russian Federation)


    Although ambient air pollution is known to affect human, quantitative measure of the impact is quite uncertain. One of the most successful approaches to evaluate adverse health consequences caused by actual concentrations of pollutants in ambient air, is risk assessment. The quantitative values of lifetime risk units recommended by international and some national organizations are often used in assessing the health risk from different sources (chemical pollutants, radioactive exposure, electromagnetic fields etc.). Recommendations of the World Health Organisation and United States Environmental Protection Agency in the Integrated Risk Data Base were taken for a basis in calculating health risks caused by chemically polluted ambient air in Russian cities. We also used well established approaches for assessing health risks from the substances not clearly defined in terms of risk units in the mentioned recommendations. In all cases, expert values of risks have been averaged, and the uncertainty range reflects the differences in the risk recommendations and the inaccuracies in methods used for measuring air pollutants.

  20. Combination of Human Fas (CD95/Apo-1) Ligand with Adriamycin Significantly Enhances the Efficacy of Antitumor Response

    Institute of Scientific and Technical Information of China (English)

    Zhongchen Liu; Ruizhen Liu; Jinhua Qiu; Ping Yin; Fanghong Luo; Jinhua SU; Wenzhu Li; Caixia Chen; Xin Fan; Jiakai Zhang; Guohong Zhuang


    The prognosis of hepatocellular carcinoma (HCC) is poor, even with the combined treatment of curative resection and adjuvant chemoradiotherapy. To solve this problem, many biologic therapies have been investigated. Fas ligand (FasL, CD95L) is mainly expressed in activated T lymphocytes and natural killer (NK) cells, and plays a central role in both cell-mediated immunity and immune downregnlation. Several studies have shown that FasL is expressed in HCC. In the present report, we prepared recombinant human pET-22b(+)/FasL protein and investigated the effect of FasL on HCC cells in vitro and on tumor growth in a murine HCC tumor model. The well-known cytotoxic chemotherapeutic reagent adriamycin (ADM) served as a control. We found that FasL effectively suppressed the viability of H22 tumor cells and significantly induced the apoptosis of H22 cells. The apoptotic levels of cells treated with FasL-ADM were significantly higher than those treated with FasL or ADM alone, and the FasL-ADM combination resulted in a more than additive effect on tumor growth delay in this model. The results suggested that combined treatment of FasL and other chemotherapeutic agents 5 be a new approach to improve the efficacy of chemotherapy for HCC. Cellular & Molecular Immunology. 2009;6(3):167-174.

  1. Lack of association of apoE ε4 allele with insulin resistance. (United States)

    Ragogna, Francesca; Lattuada, Guido; Ruotolo, Giacomo; Luzi, Livio; Perseghin, Gianluca


    ApoE is a polymorphic protein involved in the metabolism of plasma lipoproteins; the ε4 allele was shown to be associated with coronary and aortic atherosclerosis in age-dependent fashion mediated by unknown mechanisms. This study was undertaken to assess whether the apoE isoforms in humans were associated with normal glucose tolerance and with metabolic and inflammatory risk factors of CVD. ApoE genotype was assessed in 365 individuals. Of those, 309 were studied in the postabsorptive conditions and 142 of them also underwent a 3h-OGTT; 56 additional subjects were studied by means of the insulin clamp in combination with [6,6-2H2] glucose infusion. ApoE genotype frequencies were similar to those previously reported and were not influenced by age and BMI. Fasting plasma glucose, insulin, FFA, the lipid profile, surrogate markers (HOMA-IR, OGTT-derived index) as well as the clamp-derived parameters or insulin sensitivity and insulin secretion were not different by apoE genotypes. Serum adipokines concentrations (leptin, adiponectin, resistin) and markers of inflammation (serum fasting hsCRP and MCP1/CCL2) were also not different by apoE genotypes. In the subgroup of young ε4 carriers which underwent the clamp procedure, a higher fasting endogenous glucose production was detected. ApoE genotype was not associated with insulin resistance or altered insulin secretion, and no abnormalities in the typical circulating endocrine, metabolic, and inflammatory features of the insulin resistance syndrome were detected.

  2. Crystal balls, virtual realities and &apos;storylines&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Courtney, R.S.


    &apos;'Projections'&apos; of anthropogenic climate change reported in the Third Assessment Report (TAR) of the UN Intergovernmental Panel on Climate Change (IPCC) are assessed to be based on pseudo-science. (author)

  3. Future human resources development in British Columbia&apos;s offshore oil and gas industry : preliminary analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jothen, K. [Human Capital Strategies, Victoria, BC (Canada)


    Since 2001, three major studies have concluded that there are no apparent scientific or technological impediments to lifting a longstanding moratorium on West Coast oil and gas exploration and development. Over 300 occupations are involved in offshore oil and gas activity, and should the moratorium be lifted, labour demand is projected to reach 27,000 new employment openings. This report presents a preliminary analysis of factors that may facilitate offshore oil and gas development in British Columbia (BC), with specific reference to human resources. The report also highlights the broader planning environment of BC offshore oil and gas development and the potential impacts of economic, social, demographic and political factors. Potential gaps in regional training resources were identified within the context of a general overview of education training programs currently available elsewhere. Demand pressures on the supply of skilled labour for future development were considered. Interviews with key industry and stakeholder representatives were conducted. Additionally, a comparison of labour demand from oil and gas development on the east coast revealed a significant employment multiplier impact of offshore activities, averaging 3 jobs per 1 offshore job. An outline of previous employment growth patterns were provided for future reference. It was concluded that early planning and development of educational and training programs is essential in addressing eventual skills shortages. In addition to training measures, a range of public policy options should be considered, including retention measures to remove regulatory disincentives and innovative local agreements. Steps to rectify shortages in trades workers, technicians and experienced production workers is advisable, as these shortages are already evident in current onshore oil and gas activities elsewhere in Canada. A detailed description of offshore oil and gas occupations was provided, as well as questionnaires

  4. Suppression of c-Myc is involved in multi-walled carbon nanotubes&apos; down-regulation of ATP-binding cassette transporters in human colon adenocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhaojing [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China); Xu, Yonghong [Institute of Ophthalmological Research, Department of Ophthalmology, Renmin Hospital of Wuhan University, 430060 Wuhan (China); Meng, Xiangning [School of Materials and Metallurgy, Northeastern University, Shenyang 110819 (China); Watari, Fumio [Department of Biomedical, Dental Materials and Engineering, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586 (Japan); Liu, Hudan, E-mail: [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China); Chen, Xiao, E-mail: [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China)


    Over-expression of ATP-binding cassette (ABC) transporters, a large family of integral membrane proteins that decrease cellular drug uptake and accumulation by active extrusion, is one of the major causes of cancer multi-drug resistance (MDR) that frequently leads to failure of chemotherapy. Carbon nanotubes (CNTs)-based drug delivery devices hold great promise in enhancing the efficacy of cancer chemotherapy. However, CNTs&apos; effects on the ABC transporters remain under-investigated. In this study, we found that multiwalled carbon nanotubes (MWCNTs) reduced transport activity and expression of ABC transporters including ABCB1/Pgp and ABCC4/MRP4 in human colon adenocarcinoma Caco-2 cells. Proto-oncogene c-Myc, which directly regulates ABC gene expression, was concurrently decreased in MWCNT-treated cells and forced over-expression of c-Myc reversed MWCNTs&apos; inhibitory effects on ABCB1 and ABCC4 expression. MWCNT-cell membrane interaction and cell membrane oxidative damage were observed. However, antioxidants such as vitamin C, β-mecaptoethanol and dimethylthiourea failed to antagonize MWCNTs&apos; down-regulation of ABC transporters. These data suggest that MWCNTs may act on c-Myc, but not through oxidative stress, to down-regulate ABC transporter expression. Our findings thus shed light on CNTs&apos; novel cellular effects that may be utilized to develop CNTs-based drug delivery devices to overcome ABC transporter-mediated cancer chemoresistance.

  5. Posterior &apos;'Nutcracker'&apos; phenomenon in a patient with abdominal aortic aneurysm

    Energy Technology Data Exchange (ETDEWEB)

    Puig, Stefan [Department of Radiology, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Department of Emergency Medicine, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Stuehlinger, Hermann Georg; Domanovits, Hans [Department of Emergency Medicine, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Staudenherz, Anton [Department of Emergency Medicine, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Department of Nuclear Medicine, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Zebenholzer, Karin [Department of Emergency Medicine, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Department of Neurology, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Rebhandl, Winfried [Department of Surgery, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Prokop, Mathias [Department of Radiology, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)


    We report on a posterior &apos;'nutcracker'&apos; phenomenon due to an abdominal aortic aneurysm in a patient with a retro-aortic left renal vein. A 71-year-old man with a known abdominal aortic aneurysm presented in the emergency room with mild hematuria and flank pain. Computed tomography angiography revealed an aortic aneurysm, which compressed the left renal vein between the aorta and the vertebral column. Compression of the left renal vein, due to the aorta with consecutive congestion and hematuria as well as flank pain, was previously described as nutcracker phenomenon. In case of a retro-aortic left renal vein, increase of the aortic diameter can lead to compression of the renal vein and furthermore to the classical signs and symptoms of the &apos;'nutcracker'&apos; phenomenon, even though the aneurysm is not ruptured or there are no aorto-caval or aorto-left renal vein fistulas. (orig.)

  6. Town with energy efficiency - SEE - Stuttgart: Flagship project &apos;'Wilhelma'&apos;; Stadt mit Energieeffizienz - SEE - Stuttgart. Leuchtturmprojekt &apos;'Wilhelma'&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Hilse, Annika [Stuttgart Univ. (Germany). Inst. fuer Siedlungswasserbau, Wasserguete- und Abfallwirtschaft; Fischer, Klaus; Kranert, Martin


    In the context of the project &apos;&apos;Stuttgart - city with energy efficiency&apos;&apos; (SEE) energy flows of the city of Stuttgart will be analyzed for a more efficient use of resources and to build up a more sustainable energy concept for the city. The Institute for sanitary engineering, water quality and solid waste management is responsible for drafting an experts report for biomass potentials of Stuttgart&apos;s Wilhelma zoo. Since 1953 the Wilhelma is a zoological garden and today one of the zoos with the highest density of species in Germany. With an extension of the park area from about 230 ha, including castle and palace garden, and due to its large number of greater mammals, the Wilhelma is expected to provide a sufficient biomass potential to run a biogas plant. Needs analyses will be followed by an analysis of potentials, which determines energy and heat demand in quantity and time to run the zoo. In addition, further supply concepts for renewable energy use, p. ex. solar panels at roofs of operation buildings, will be assessed and evaluated by the Institute for Energy Economics and Rational Use of Energy (IER). The Wilhelma&apos;s own biogas plant will exemplify the way of self-sufficient energy and heat supply. It will show optimal energy saving in downtown facilities and will therefore be a &apos;&apos;flakship project&apos;&apos; in the SEE-project. In the project a possibility to replace decentral - fossil fuels with local - renewable energies can be shown as an example for implementation of integrated regional bioenergy concepts. (orig.)

  7. Principles and some applications of &apos;&apos;zero field nuclear magnetic resonance&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Llor, A.; Virlet, J.


    The method known as &apos;&apos;zero field NMR&apos;&apos; is reviewed. The technique allows the observation of nuclear dipolar and quadrupolar interactions in powder samples, which may otherwise be possible in high field on monocristals only. The anisotropy due to the magnetic field is removed although sensitivity is preserved. This method is compared to other Nuclear Resonance spectroscopies: its originality lies in the measurement of the coherent evolution of the system in zero field after a perturbation induced by suddenly switching the magnetic field. The Fourier transform of the &apos;&apos;zero field free induction decay&apos;&apos; then gives the &apos;&apos;zero field spectrum&apos;&apos;. The ideal experiment is described with its adaptations due to experimental constraints, as realized in our laboratory at Saclay and in the laboratory of A. Pines at Berkeley. We present with our first measurements a review of most of the results published to date on spin 1/2 as well as spin 1/2 (quadrupolar) nuclei. Possible future developments of the method are also discussed.

  8. Fossil sources: &apos;&apos;Running out&apos;&apos; is not the problem

    Energy Technology Data Exchange (ETDEWEB)

    Scott, D.S. [Victoria Univ., BC (Canada). Inst. for Integrated Energy System


    In which we discuss reserves, resources and the mythology that, sooner or later, our fossil sources will be gone. Then, to help appreciate the real reason fossil reserves will ultimately vanish, we evoke Weary Willie&apos;s clown routine &apos;sweeping up the spotlight.&apos; (Author)

  9. Physiological response to &apos;'pressure-demand'&apos; respirator wear

    Energy Technology Data Exchange (ETDEWEB)

    Raven, P.B.; Bradley, O.; Rohm-Young, D.; McClure, F.L.; Skaggs, B.


    This investigation determined cardiorespiratory responses of subjects with normal lung function and exercise tolerance and compared them with subjects with moderate impairment of lung function and exercise tolerance. The respirator was an air-line full-face mask (MSA-Ultravue) &apos;'pressure-demand'&apos; breathing type equipped with an inspiratory resistance of 85 mmH/sub 2/0 at 85 L/min air flow. This resistance was operable in conjunction with the fixed 25 mmH/sub 2/O inspiratory and expiratory resistance required to pressurize the face piece. Physiologically and subjectively the response of the normal and moderately impaired subjects to respirator wear during rest, 35%, 50% and 80% of their maximal aerobic capacity (VO/sub 2//sub max/) were not different. However, the pressure swings inside the face piece exceeded 24 cm H/sub 2/O and resulted in 50% of the subjects being unable to finish 10 minutes of work at 80% VO/sub 2//sub max/. The greater the ventilatory demand placed upon the respirator due to increasing workload, the more like a &apos;'demand'&apos; system pressure-flow response the &apos;'pressure-demand'&apos; system produced. Hence, the concept of increased protection and reduced inspiratory resistance as a result of pressurizing the facepiece during heavy work is seriously questioned.

  10. &apos;Carbon-Money Exchange&apos; to contain global warming and deforestation

    Energy Technology Data Exchange (ETDEWEB)

    Nagase, Kozo E-mail:


    This paper builds a basic theory of &apos;Carbon-Money Exchange&apos; in which carbon as currency in nature&apos;s household (ecosystems) and money as currency in humankind&apos;s household (economy) are exchanged just like in a foreign exchange. The simple chemical equation below makes it possible (CO{sub 2}{yields}C+O{sub 2}=C+O{sub 2}{yields}CO{sub 2}). The left-hand side represents the work of plants to remove atmospheric CO{sub 2}. The right-hand side represents the work of humans as fossil fuel consumers to produce it. The exchange of the two currencies is possible by copying the fossil fuel market. The paper concludes that this new exchange can automatically contain global warming and deforestation, replacing onerous emissions trading. Moreover, it could revolutionize the conventional economy, creating counter-capitalism, or &apos;carbonism&apos;.

  11. Immunolocalization of cubilin, megalin, apolipoprotein J, and apolipoprotein A-I in the uterus and oviduct. (United States)

    Argraves, W Scott; Morales, Carlos R


    Spermatozoa maturation and capacitation occurring in the male and female reproductive tracts, respectively, involves the remodeling of the spermatozoa plasma membrane. Apolipoprotein J (apoJ) and apolipoprotein A-I (apoA-I) have been implicated in the process of lipid exchange from the spermatozoa plasma membrane to epithelial cells lining the male reproductive tract. Evidence suggests that this process is mediated by the cooperative action of the endocytic lipoprotein receptors megalin and cubilin, which are expressed at the apical surface of absorptive epithelia in various tissues, including the efferent ducts and epididymis. Here, we investigated the possibility that these receptors and their lipid-binding ligands, apoJ and apoA-I, might function similarly in the female reproductive tract. We show that megalin and cubilin are expressed in the uterine epithelium at all stages of the estrous cycle, maximally during estrous and metestrous stages. In the oviduct, there is pronounced expression of both megalin and cubilin in the nonciliated cells of the proximal oviduct and epithelial cells of the distal oviduct, particularly during estrous and metestrous stages. In both uterine and oviduct epithelial cells, megalin and cubilin were located on the apical regions of the cells, consistent with a distribution at the cell surface and in endosomes. ApoJ and apoA-I were both detected in apical regions of uterine and oviduct epithelial cells. Secretory cells of the uterine glands were found to express apoJ and apoA-I suggesting that the glands are a site of synthesis for both proteins. In summary, our findings indicate that megalin and cubilin function within the female reproductive tract, possibly mediating uterine and oviduct epithelial cell endocytosis of apoJ/apoA-I-lipid complexes and thus playing a role in lipid efflux from the sperm plasma membrane, a major initiator of capacitation.

  12. 2001 &apos;&apos;You Have the Power&apos;&apos; campaign [Federal Energy Management Program]. Final technical report

    Energy Technology Data Exchange (ETDEWEB)



    The Tasks of 2001 &apos;&apos;You Have the Power&apos;&apos; campaign by the Federal Energy Management Program (FEMP) are: Task 1--Interagency Planning Meetings; Task 2--Ear Day Event; Task 3--Earth Day and Energy Awareness Month Activities; Task 4--Regional Target; Task 5--Outreach Tools and Campaign Products; Task 6--Private Sector Participation; Task 7--&apos;&apos;You Have the Power&apos;&apos; on the FEMP Web Site; and Task 8--Effective Communications.

  13. Triglyceride-rich lipoprotein metabolism in women: roles of apoC-II and apoC-III. (United States)

    Ooi, Esther M; Chan, Dick C; Hodson, Leanne; Adiels, Martin; Boren, Jan; Karpe, Fredrik; Fielding, Barbara A; Watts, Gerald F; Barrett, P Hugh R


    Experimental data suggest that apolipoprotein (apo) C-II and C-III regulate triglyceride-rich lipoprotein (TRL) metabolism, but there are limited studies in humans. We investigated the metabolic associations of TRLs with apoC-II and apoC-III concentrations and kinetics in women. The kinetics of plasma apoC-II, apoC-III and very low-density lipoprotein (VLDL) apoB-100 and triglycerides were measured in the postabsorptive state using stable isotopic techniques and compartmental modelling in 60 women with wide-ranging body mass index (19·5-32·9 kg/m(2) ). Plasma apoC-II and apoC-III concentrations were positively associated with the concentrations of plasma triglycerides, VLDL1 - and VLDL2 -apoB-100 and triglyceride (all P triglyceride concentration and VLDL1 triglyceride PR, while apoC-II fractional catabolic rate (FCR) was positively associated with VLDL1 triglyceride FCR (all P triglyceride kinetics. ApoC-III PR, but not FCR, was positively associated with VLDL1 triglyceride, and VLDL2 -apoB-100 and triglyceride concentrations (all P triglyceride kinetics. In multivariable analysis, including homoeostasis model assessment score, menopausal status and obesity, apoC-II concentration was significantly associated with plasma triglyceride, VLDL1 -apoB-100 and VLDL1 triglyceride concentrations and PR. Using the same multivariable analysis, apoC-III was significantly associated with plasma triglyceride and VLDL1 - and VLDL2 -apoB-100 and triglyceride concentrations and FCR. In women, plasma apoC-II and apoC-III concentrations are regulated by their respective PR and are significant, independent determinants of the kinetics and plasma concentrations of TRLs. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  14. &apos;&apos;Activity based costing&apos;&apos; in radiology; &apos;&apos;Activity based costing&apos;&apos; in der Radiologie

    Energy Technology Data Exchange (ETDEWEB)

    Klose, K.J. [Klinik fuer Strahlendiagnostik, Medizinisches Zentrum fuer Radiologie, Philipps-Universitaet, Marburg (Germany); Boettcher, J. [pphc GmbH, Ammersbeck (Germany)


    Background: The introduction of diagnosis related groups for reimbursement of hospital services in Germany (g-drg) demands for a reconsideration of utilization of radiological products and costs related to them. Methods: Traditional cost accounting as approach to internal, department related budgets are compared with the accounting method of activity based costing (ABC). The steps, which are necessary to implement ABC in radiology are developed.Conclusions: The introduction of a process-oriented cost analysis is feasible for radiology departments. ABC plays a central role in the set-up of decentralized controlling functions within this institutions. The implementation seems to be a strategic challenge for department managers to get more appropriate data for adequate enterprise decisions. The necessary steps of process analysis can be used for other purposes (Certification, digital migration) as well. (orig.) [German] Hintergrund. Die Oekonomisierung der Medizin in Deutschland, die in der beabsichtigten Einfuehrung der kostenhomogenen Verguetungsklassen nach den &apos;&apos;diagnosis related groups - DRG&apos;s'&apos; ihren vorlaeufigen Hoehepunkt finden soll, erfordert eine Neuorientierung im Einsatz und in der Beurteilung der Wirtschaftlichkeit radiologischer Verfahren.Methode. Traditionelle Kostenrechnungen bzw. Verfahren zur internen Budgetierung werden der Prozesskostenbetrachtung (&apos;&apos;activity based costing&apos;&apos; - ABC) gegenuebergestellt, deren auf radiologische Belange zugeschnittene Methodik Schritt fuer Schritt entwickelt wird.Ergebnisse. Die Betrachtung radiologischer Arbeitsprozesse auf der Basis des ABC gestattet anhand der bisher publizierten Ergebnisse eine bessere Einschaetzung von Steuerungsimpulsen, die zu einer Effizienzsteigerung in radiologischen Prozessen fuehren koennen.Schlussfolgerungen. Die Einfuehrung einer prozessorientierten Kostenanalyse ist fuer vielfaeltige Belange einer Radiologieabteilung moeglich. Sie stellt

  15. Blood serum apolipoproteins B and A-I in females suffering from rheumatic heart valve disease. (United States)

    Stakisaitis, Donatas; Maksvytis, Arūnas; Salcius, Kestutis; Benetis, Rimantas


    With the aim to check whether the atherogenic factors are involved in the mechanisms of valve fibrosis, we have studied the blood serum concentrations of apolipoproteins (apo) A-I and B concentration in patients suffering from rheumatic heart valve fibrosis. The quantities of apoA-I and apoB in the blood serum were tested by the ELISA method. Concentration of apoA-I and B in the blood serum was determined in rheumatic females with replacement of the damaged valves: after aortic valve operation (n=11; mean age 43.3+/-3.6 years) and after mitral valve operation (n=29; 41.3+/-4.1). The results obtained for rheumatic patients were compared with the data on age-matched healthy females (n=43; 39.5+/-5.2 years). Significantly lower apoA-I level in the blood serum of all patients suffering from rheumatic heart valve disease was determined as compared with controls: in the pooled group of patients (1.02+/-0.22 vs 1.23+/-0.23 g/l, Pvalve replacement (0.98+/-0.21 vs. 1.23+/-0.23 g/l, Pvalve surgery (1.03+/-0.23 g/l vs 1.23+/-0.23 g/l, Pheart valve disease did not differ from that of controls. The apoB/apoA-I ratio for patients with valve fibrotic damage was significantly higher as compared to controls in all groups (Pvalve fibrosis was caused by lower apoA-I levels in blood serum. The obtained results indicate that decreased apoA-I levels in blood serum can be indicative of valve fibrosis in rheumatic heart valve disease patients.

  16. Anti-interleukin-1 alpha autoantibodies in humans: Characterization, isotype distribution, and receptor-binding inhibition--higher frequency in Schnitzler&apos;s syndrome (urticaria and macroglobulinemia)

    Energy Technology Data Exchange (ETDEWEB)

    Saurat, J.H.; Schifferli, J.; Steiger, G.; Dayer, J.M.; Didierjean, L. (Department of Dermatology, University Hospital, Geneva (Switzerland))


    Since autoantibodies (Abs) to cytokines may modify their biologic activities, high-affinity binding factors for interleukin-1 alpha (IL-1 alpha BF) were characterized in human sera. IL-1 alpha BF was identified as IgG (1) by sucrose density-gradient centrifugation followed by immunodiffusion autoradiography, (2) by ligand-blotting method, (3) by ligand binding to affinity-immobilized serum IgG, and (4) by IgG affinity purification followed by sucrose density-gradient centrifugation. IL-1 alpha binding activity resided in the F(ab)2 fragment. The apparent equilibrium constant was in the range of IgG found after immunization with conventional antigens (i.e., 10(-9) to 10(-10) mol/L). Anti-IL-1 alpha IgG auto-Abs represented only an extremely small fraction of total IgG (less than 1/10(-5)). Some sera with IL-1 alpha BF and purified IgG thereof were able to inhibit by 96% to 98% the binding of human recombinant IL-1 alpha to its receptor on murine thymoma EL4-6.1 cells, whereas other sera did not. When 125I-labeled anti-IL-1 alpha IgG complexes were injected into rats, they prolonged the plasma half-life of 125I-labeled IL-1 alpha several fold and altered its tissue distribution. The predominant class was IgG (12/19), mainly IgG4 (9/19), but in five of the sera, anti-IL-1 alpha IgA was also detected. In a screening of 271 sera, IL-1 alpha BF was detected in 17/98 normal subjects and was not more frequent in several control groups of patients, except in patients with Schnitzler&apos;s syndrome (fever, chronic urticaria, bone pain, and monoclonal IgM paraprotein) (6/9; p less than 0.005). The pathologic significance of these auto-Abs remains to be determined.

  17. Role of apolipoprotein A-II in the structure and remodeling of human high-density lipoprotein (HDL): protein conformational ensemble on HDL. (United States)

    Gao, Xuan; Yuan, Shujun; Jayaraman, Shobini; Gursky, Olga


    High-density lipoproteins (HDL, or "good cholesterol") are heterogeneous nanoparticles that remove excess cell cholesterol and protect against atherosclerosis. The cardioprotective action of HDL and its major protein, apolipoprotein A-I (apoA-I), is well-established, yet the function of the second major protein, apolipoprotein A-II (apoA-II), is less clear. In this review, we postulate an ensemble of apolipoprotein conformations on various HDL. This ensemble is based on the crystal structure of Δ(185-243)apoA-I determined by Mei and Atkinson combined with the "double-hairpin" conformation of apoA-II(dimer) proposed in the cross-linking studies by Silva's team, and is supported by the wide array of low-resolution structural, biophysical, and biochemical data obtained by many teams over decades. The proposed conformational ensemble helps integrate and improve several existing HDL models, including the "buckle-belt" conformation of apoA-I on the midsize disks and the "trefoil/tetrafoil" arrangement on spherical HDL. This ensemble prompts us to hypothesize that endogenous apoA-II (i) helps confer lipid surface curvature during conversion of nascent discoidal HDL(A-I) and HDL(A-II) containing either apoA-I or apoA-II to mature spherical HDL(A-I/A-II) containing both proteins, and (ii) hinders remodeling of HDL(A-I/A-II) by hindering the expansion of the apoA-I conformation. Also, we report that, although endogenous apoA-II circulates mainly on the midsize spherical HDL(A-I/A-II), exogenous apoA-II can bind to HDL of any size, thereby slightly increasing this size and stabilizing the HDL assembly. This suggests distinctly different effects of the endogenous and exogenous apoA-II on HDL. Taken together, the existing results and models prompt us to postulate a new structural and functional role of apoA-II on human HDL.

  18. Preparation of soluble apolipoproteins A-I, B, and C-II by a chromatofocusing column method, and evaluation of their concentrations in serum in pulmonary disease. (United States)

    Jauhiainen, M; Laitinen, M; Marniemi, J; Liippo, K; Penttilä, I; Hietanen, E


    A chromatofocusing column method for isolating ApoB is described. LDL is first isolated by sequential ultracentrifugation and delipidated with n-butanol/diisopropyl ether. Chromatofocusing of ApoLDL yielded a large ApoB peak at pI 5.0-5.3. ApoA-I and ApoC-II were prepared analogously, with HDL and VLDL as the source of apoprotein. Antisera were raised in rabbits, and electroimmunoassay techniques were used for determination. ApoB was water-soluble after chromatofocusing. Intra-assay precision (CV) was 4.7% for ApoA-I, 7.8% for ApoB in the "rocket" electrophoresis. Interassay precision (CV) was 6% for ApoA-I and 8% for ApoB. Apolipoprotein concentrations were measured in subjects who had undergone lung resection and patients with obstructive pulmonary disease. After lung resection, the concentration of ApoA-I in serum was significantly decreased (p less than 0.001) and that of ApoB significantly increased (p less than 0.001) as compared with controls. The ApoA-I/ApoB ratio was significantly lower in the lung-resection group. ApoA-I and ApoB concentrations were unchanged in chronic obstructive pulmonary disease. ApoC-II concentrations in each group were similar to those for control subjects. Of the lipids, values for total cholesterol were above normal after lung resection (p less than 0.002), as were those for triglycerides (p less than 0.02).

  19. The German &apos;'Energiewende'&apos;. Evaluation after the Paris-agreement; Die Deutsche Energiewende. Bewertung nach dem Klima-Abkommen von Paris

    Energy Technology Data Exchange (ETDEWEB)

    Roth, Eike


    The World-Climate-Summit 2016 in Paris agreed to exacerbated goals for climate protection. This paper will scrutinize whether Germany can comply with its Paris-obligations by continuing the ongoing German &apos;'Energiewende'&apos;. The result is clear-cut: The German &apos;'Energiewende'&apos; is inadequate. Due to the cap-and-trade system of the EU the &apos;''Energiewende'&apos;.

  20. Glyoxalase 1 overexpression does not affect atherosclerotic lesion size and severity in ApoE-/- mice with or without diabetes. (United States)

    Hanssen, Nordin M J; Brouwers, Olaf; Gijbels, Marion J; Wouters, Kristiaan; Wijnands, Erwin; Cleutjens, Jack P M; De Mey, Jo G; Miyata, Toshio; Biessen, Erik A; Stehouwer, Coen D A; Schalkwijk, Casper G


    Advanced glycation end-products (AGEs) and their precursors have been associated with the development of atherosclerosis. We recently discovered that glyoxalase 1 (GLO1), the major detoxifying enzyme for AGE precursors, is decreased in ruptured human plaques, and that levels of AGEs are higher in rupture-prone plaques. We here investigated whether overexpression of human GLO1 in ApoE(-/-) mice could reduce the development of atherosclerosis. We crossed C57BL/6 ApoE(-/-) mice with C57BL/6 GLO1 overexpressing mice (huGLO1(+/-)) to generate ApoE(-/-) (n = 16) and ApoE(-/-) huGLO1(+/-) (n = 20) mice. To induce diabetes, we injected a subset with streptozotocin (STZ) to generate diabetic ApoE(-/-) (n = 8) and ApoE(-/-) huGLO1(+/-) (n = 13) mice. All mice were fed chow and sacrificed at 25 weeks of age. The GLO1 activity was three-fold increased in huGLO1(+/-) aorta, but aortic root lesion size and phenotype did not differ between mice with and without huGLO1(+/-) overexpression. We detected no differences in gene expression in aortic arches, in AGE levels and cytokines, in circulating cells, and endothelial function between ApoE(-/-) mice with and without huGLO1(+/-) overexpression. Although diabetic mice showed decreased GLO1 expression (P diabetic mice, GLO1 overexpression also did not affect the aortic root lesion size or inflammation in diabetic mice. In ApoE(-/-) mice with or without diabetes, GLO1 overexpression did not lead to decreased atherosclerotic lesion size or systemic inflammation. Increasing GLO1 levels does not seem to be an effective strategy to reduce glycation in atherosclerotic lesions, likely due to increased AGE formation through GLO1-independent mechanisms. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email:

  1. Online trapping and enrichment ultra performance liquid chromatography-tandem mass spectrometry method for sensitive measurement of &apos;arginine-asymmetric dimethylarginine cycle&apos; biomarkers in human exhaled breath condensate

    Energy Technology Data Exchange (ETDEWEB)

    Di Gangi, Iole Maria, E-mail: [Chromatography and Mass Spectrometry Laboratory, Department of Women' s and Children' s Health, University of Padova (Italy); Pirillo, Paola [Chromatography and Mass Spectrometry Laboratory, Department of Women' s and Children' s Health, University of Padova (Italy); Carraro, Silvia [Unit of Allergy and Respiratory Diseases, Department of Women' s and Children' s Health, University of Padova (Italy); Gucciardi, Antonina; Naturale, Mauro [Chromatography and Mass Spectrometry Laboratory, Department of Women' s and Children' s Health, University of Padova (Italy); Baraldi, Eugenio [Unit of Allergy and Respiratory Diseases, Department of Women' s and Children' s Health, University of Padova (Italy); Giordano, Giuseppe [Chromatography and Mass Spectrometry Laboratory, Department of Women' s and Children' s Health, University of Padova (Italy)


    Highlights: Black-Right-Pointing-Pointer Simultaneous quantification of &apos;arginine-ADMA cycle&apos; metabolites developed in EBC. Black-Right-Pointing-Pointer EBC is a non-invasive matrix highly useful in patients with respiratory diseases. Black-Right-Pointing-Pointer Method, fast, precise and accurate, is suitable in the pediatric clinical studies. Black-Right-Pointing-Pointer Sensitivity is increased using on-line trapping and enrichment-UPLC-MS/MS method. Black-Right-Pointing-Pointer EBC measurements in asthmatic adolescents confirm that ADMA is increased in asthma. - Abstract: Background: Exhaled breath condensate (EBC) is a biofluid collected non invasively that, enabling the measurement of several biomarkers, has proven useful in the study of airway inflammatory diseases, including asthma, COPD and cystic fibrosis. To the best of our knowledge, there is no previous report of any analytical method to detect ADMA in EBC. Objectives: Aim of this work was to develop an online sample trapping and enrichment system, coupled with an UPLC-MS/MS method, for simultaneous quantification of seven metabolites related to &apos;Arginine-ADMA cycle&apos;, using the isotopic dilution. Methods: Butylated EBC samples were trapped in an online cartridge, washed before and after each injection with cleanup solution to remove matrix components and switched inline into the high pressure analytical column. Multiple reaction monitoring in positive mode was used for analyte quantification by tandem mass spectrometry. Results: Validation studies were performed in EBC to examine accuracy, precision and robustness of the method. For each compound, the calibration curves showed a coefficient of correlation (r{sup 2}) greater than 0.992. Accuracy (%Bias) was <3% except for NMMA and H-Arg (<20%), intra- and inter-assay precision (expressed as CV%) were within {+-}20% and recovery ranged from 97.1 to 102.8% for all analytes. Inter-day variability analysis on 20 EBC of adult subjects did

  2. ApoE (Apolipoprotein E) Genotyping (United States)

    ... Home Visit Global Sites Search Help? APOE Genotyping, Alzheimer Disease Share this page: Was this page helpful? Formal ... help in the diagnosis of probable late onset Alzheimer disease (AD) in symptomatic adults. It is called susceptibility ...

  3. European day &apos;&apos;in town, without my car&apos;&apos;; Journee europeen &apos;&apos;en ville, sans ma voiture&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)



    70 million inhabitants took part in the day &apos;&apos;In town, without my car&apos;&apos; on 22 September of this year. It is a great success for this European first. The objective of Energie-Cites association being to promote sustainable local energy policies, that is to say policies aimed at improving energy efficiency, increasing the use of renewable energy sources and limiting nuisance and pollution linked to energy consumption, the association is pleased that this event helped focus public attention on transport. It is indeed in this sector that uncontrolled upswings in energy consumption and greenhouse gas emissions are the most important. This report presents the evaluation of this European initiative and details the actions in some towns. (A.L.B.)

  4. Endotoxin contamination of apolipoprotein A-I: effect on macrophage proliferation--a cautionary tale. (United States)

    Jin, Xueting; Xu, Qing; Champion, Keith; Kruth, Howard S


    This technical report addresses the problem of endotoxin contamination of apolipoprotein reagents. Using a bromodeoxyuridine incorporation cell proliferation assay, we observed that human plasma ApoA-I as low as 1 μg/ml resulted in a >90% inhibition in macrophage proliferation. However, not all ApoA-I from different sources showed this effect. We considered the possibility that endotoxin contamination of the apolipoproteins contributed to the differential inhibition of macrophage cell proliferation. Endotoxin alone very potently inhibited macrophage proliferation (0.1 ng/ml inhibited macrophage proliferation>90%). Measurement of endotoxin levels in the apolipoprotein products, including an analysis of free versus total endotoxin, the latter which included endotoxin that was masked due to binding to protein, suggested that free endotoxin mediated inhibition of macrophage proliferation. Despite the use of an advanced endotoxin removal procedure and agents commonly used to inhibit endotoxin action, the potency of endotoxin precluded successful elimination of endotoxin effect. Our findings show that endotoxin contamination can significantly influence apparent apolipoprotein-mediated cell effects (or effects of any other biological products), especially when these products are tested on highly endotoxin-sensitive cells, such as macrophages.

  5. Investigation of vertebral &apos;&apos;end plate sclerosis&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S.W. [Dept. of Rehabilitation Sciences, Hong Kong Polytechnic Univ., Hung Hom (Hong Kong); Mathie, A.G.; Jackson, J.E. [Diagnostic Radiology, Royal Postgraduate Medical School, Hammersmith Hospital, London (United Kingdom); Hughes, S.P.F. [Div. of Surgery, Anaesthetics and Intensive Care, London (United Kingdom)


    To evaluate the association between vertebral &apos;&apos;end plate sclerosis&apos;&apos; and neck pain. A retrospective study was carried out of lateral cervical spine radiographs with a Picture Archive and Communication System (PACS). Two hundred patients&apos; files were randomly assessed, comprising four equal groups, A to D. The mean ages of the patients were 62{+-}7.4 years, 61{+-}7.5 years, 40{+-}5.6 years and 23{+-}5.6 years respectively. In group A, all patients had symptoms of neck pain and a radiographic diagnosis of &apos;&apos;end plate sclerosis&apos;&apos; of the cervical spine. In groups B to D, asymptomatic patients were recruited and their age groups were 50-69, 30-49 and 10-29 years respectively. Using the PACS, the radiographic density and the sagittal diameter, thickness and area of the end plates at the C5 level were measured. Results and conclusions: No significant differences were found in the radiographic density of the end plates either between the symptomatic and asymptomatic groups (groups A and B), or between different age groups (groups B, C and D). A significant increase in end plate area and thickness was found, however, in both group B (P<0.005) and group C (P<0.01) in comparison with group D. This indicates that the extent of end plate sclerosis increases with age. Our results suggest that the radiographic density of cervical vertebral end plates correlates neither with neck pain nor with increasing age. The radiological sign of &apos;&apos;end plate sclerosis&apos;&apos; may be over-reported, further limiting its value in the assessment of patients with cervical spondylosis. (orig.)

  6. Quantitation of species differences in albumin–ligand interactions for bovine, human and rat serum albumins using fluorescence spectroscopy: A test case with some Sudlow&apos;s site I ligands

    Energy Technology Data Exchange (ETDEWEB)

    Poór, Miklós [Institute of Laboratory Medicine, University of Pécs, Ifjúság u. 13, Pécs H-7624 (Hungary); Li, Yin; Matisz, Gergely [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, Pécs H-7624 (Hungary); Kiss, László [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); Kunsági-Máté, Sándor [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, Pécs H-7624 (Hungary); Kőszegi, Tamás, E-mail: [Institute of Laboratory Medicine, University of Pécs, Ifjúság u. 13, Pécs H-7624 (Hungary)


    Albumin, the most abundant plasma protein is an approximately 67 kDa sized water-soluble macromolecule. Since several drugs and xenobiotics circulate in the blood at least partially in albumin-bound form, albumin plays a key role in the pharmacokinetics/toxicokinetics of these chemicals. Most of the drugs and xenobiotics are Sudlow&apos;s site I ligands. In numerous studies, bovine serum albumin (BSA) is used for modeling albumin–ligand interactions and the results are extrapolated to human serum albumin (HSA). Furthermore, only limited information is available related to albumin–ligand interactions of different albumin species. Therefore, in our study, we have focused on the quantification of differences between bovine, human and rat serum albumin (RSA) using four Sudlow&apos;s site I ligands (luteolin, ochratoxin A, phenylbutazone and warfarin). Interactions were analyzed by fluorescence spectroscopy. Stability constants as well as competing capacities of the ligands were determined, and thermodynamic study was also performed. Our results highlight that there could be major differences between BSA, HSA and RSA in their ligand binding properties. Based on our observations we emphasize that in molecular aspects BSA behaves considerably differently from HSA or from albumins of other species therefore, it is strongly recommended to apply at least some confirmatory measurements when data obtained from other species are attempted to be extrapolated to HSA. -- Highlights: • Albumin–ligand interactions of human, bovine and rat albumins were studied. • Four Sudlow&apos;s site I ligands were tested by fluorescence spectroscopy. • Substantial differences were found in stability constants among albumin complexes. • Competing capacity of ligands showed major differences in the studied species. • Data obtained for BSA cannot be directly extrapolated to human albumin.

  7. Lipid-free Apolipoprotein A-I Structure: Insights into HDL Formation and Atherosclerosis Development (United States)

    Mei, Xiaohu; Atkinson, David


    Apolipoprotein A-I is the major protein in high-density lipoprotein (HDL) and plays an important role during the process of reverse cholesterol transport (RCT). Knowledge of the high-resolution structure of full-length apoA-I is vital for a molecular understanding of the function of HDL at the various steps of the RCT pathway. Due to the flexible nature of apoA-I and aggregation properties, the structure of full-length lipid-free apoA-I has evaded description for over three decades. Sequence analysis of apoA-I suggested that the amphipathic α-helix is the structural motif of exchangeable apolipoprotein, and NMR, X-ray and MD simulation studies have confirmed this. Different laboratories have used different methods to probe the secondary structure distribution and organization of both the lipid-free and lipid-bound apoA-I structure. Mutation analysis, synthetic peptide models, surface chemistry and crystal structures have converged on the lipid-free apoA-I domain structure and function: the N-terminal domain [1–184] forms a helix bundle while the C-terminal domain [185–243] mostly lacks defined structure and is responsible for initiating lipid-binding, aggregation and is also involved in cholesterol efflux. The first 43 residues of apoA-I are essential to stabilize the lipid-free structure. In addition, the crystal structure of C-terminally truncated apoA-I suggests a monomer-dimer conversation mechanism mediated through helix 5 reorganization and dimerization during the formation of HDL. Based on previous research, we have proposed a structural model for full-length monomeric apoA-I in solution and updated the HDL formation mechanism through three intermediate states. Mapping the known natural mutations on the full-length monomeric apoA-I model provides insight into atherosclerosis development through disruption of the N-terminal helix bundle or deletion of the C-terminal lipid-binding domain. PMID:26048453

  8. Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity

    DEFF Research Database (Denmark)

    Soerensen, Mette; Dato, Serano; Tan, Qihua


    –110) and 1,104 middle-aged Germans. rs769449 was in modest linkage equilibrium (R 2 = 0.55) with rs429358 of the APOE-ε4 haplotype and adjusting for rs429358 eliminated the association of rs769449, indicating that the association likely reflects the well-known effect of rs429358. Gene-based analysis...

  9. Education for Economic Growth or Human Development? the Capabilities Approach and the World Bank&apos;s Basic Education Project in Turkey (United States)

    McClure, Kevin R.


    Turkey&apos;s recent development plans suggest that, according to state planners, development is no longer identified with, achieved through or measured by economic growth. These documents evince that Turkey has embraced what is referred to as the capability approach. What remains unclear is whether this embrace is substantive or rhetorical. This…

  10. ECU tendon &apos;'dislocation'&apos; in asymptomatic volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Petchprapa, Catherine N. [New York University Langone Medical Center, Hospital for Joint Diseases, Department of Radiology, New York, NY (United States); Meraj, Seema [Zwanger-Pesiri Radiology Group, Lindenhurst, NY (United States); Jain, Nidhi [New York University School of Medicine, New York University Langone Medical Center, Department of Radiology, New York, NY (United States)


    Assess extensor carpi ulnaris (ECU) tendon position in the ulnar groove, determine the frequency of tendon &apos;'dislocation'&apos; with the forearm prone, neutral, and supine, and determine if an association exists between ulnar groove morphology and tendon position in asymptomatic volunteers. Axial proton density-weighted MR was performed through the distal radioulnar joint with the forearm prone, neutral, and supine in 38 asymptomatic wrists. The percentage of the tendon located beyond the ulnar-most border of the ulnar groove was recorded. Ulnar groove depth and length was measured and ECU tendon signal was assessed. 15.8 % of tendons remained within the groove in all forearm positions. In 76.3 %, the tendon translated medially from prone to supine. The tendon &apos;'dislocated'&apos; in 0, 10.5, and 39.5 % with the forearm prone, neutral and supine, respectively. In 7.9 % prone, 5.3 % neutral, and 10.5 % supine exams, the tendon was 51-99 % beyond the ulnar border of the ulnar groove. Mean ulnar groove depth and length were 1.6 and 7.7 mm, respectively, with an overall trend towards greater degrees of tendon translation in shorter, shallower ulnar grooves. The ECU tendon shifts in a medial direction when the forearm is supine; however, tendon &apos;'dislocation'&apos; has not been previously documented in asymptomatic volunteers. The ECU tendon medially translated or frankly dislocated from the ulnar groove in the majority of our asymptomatic volunteers, particularly when the forearm is supine. Overall greater degrees of tendon translation were observed in shorter and shallower ulnar grooves. (orig.)

  11. Earth in the balance. Ecology and the human spirit; Urgence Planete Terre. L&apos;esprit humain face a la crise ecologique

    Energy Technology Data Exchange (ETDEWEB)

    Al Gore


    This book is the translation of the original American edition &apos;earth in the balance&apos;. When Earth in the Balance first came out, it caused quite a stir and for good reason. It convincingly makes the case that a crisis of epidemic proportions is nearly upon us and that if the world does not get its act together soon and agree to some kind of &apos;Global Marshall Plan&apos; to protect the environment, we&apos;re all up a polluted creek without a paddle. Myriad plagues are upon us, but the worst include the loss of biodiversity, the depletion of the ozone layer, the slash-and-burn destruction of rain forests, and the onset of global warming. None of this is new, of course, nor was it new in 1992. But most environmentalists will still get a giddy feeling reading such a call to action as written by a prominent politician. The book is arranged into three sections: the first describes the plagues; the second looks at how we got ourselves into this mess; and the final chapters present ways out. Gore gets his points across in a serviceable way, though he could have benefited from a firmer editor&apos;s hand; at times the analogies are arcane and the pacing is odd kind of like a Gore speech that climaxes at weird points and then sinks just as the audience is about to clap. Still, at the end you understand what&apos;s been said. Gore believes that if we apply some American ingenuity, the twin engines of democracy and capitalism can be rigged to help us stabilize world population growth, spread social justice, boost education levels, create environmentally appropriate technologies, and negotiate international agreements to bring us back from the brink. For example, a worldwide shift to clean, renewable energy sources would create huge economic opportunities for companies large and small to design, build, and maintain solar panels, wind turbines, fuel cells, and other eco friendly innovations.

  12. The German &apos;'Energiewende'&apos;. Evaluation after the Paris-agreement; Die Deutsche Energiewende. Bewertung nach dem Klima-Abkommen von Paris

    Energy Technology Data Exchange (ETDEWEB)

    Roth, Eike


    The World-Climate-Summit 2016 in Paris agreed to exacerbated goals for climate protection. This paper will scrutinize whether Germany can comply with its Paris-obligations by continuing the ongoing German &apos;'Energiewende'&apos;. The result is clear-cut: The German &apos;'Energiewende'&apos; is inadequate. Due to the cap-and-trade system of the EU the &apos;'Energiewende'&apos; can in no way contribute to climate protection.

  13. Assessment of the biological effects of &apos;strange&apos; radiation

    Energy Technology Data Exchange (ETDEWEB)

    Pryakhin, E.A.; Tryapitsina, G.A. [Chelyabinsk State University, Chelyabinsk (Russian Federation); Urutskoyev, L.I. [RECOM Company, Kurchatov Russian Research Institute, Moscow (Russian Federation); Akleyev, A.V. [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation)


    studies: 1. &apos;strange&apos; radiation resulting from explosion of Ti foils in water and aqueous solutions has the capacity to produce a biological effect. 2. The biological effect of &apos;strange&apos; radiation is manifested by a 13% increase in the number of nucleated cells in the bone marrow, as compared to that in controls, after exposure of the animals to 10 explosions within 3 days of the experiment. 3. The assessment of micronucleus rate in the bone marrow erythrocytes did not reveal the genotoxic effect of &apos;strange&apos; radiation. 4. The exposure of mice to &apos;strange&apos; radiation resulting from 10 explosions carried out within 3 days leads to 1.5 fold decrease of genotoxic effect resulting from additional gamma-irradiation (2 Gy). Such reaction may be described as an adaptive response. 5. &apos;strange&apos; radiation resulting from 10 explosions carried out within 3 days after the gamma irradiation (6 Gy) leads to decrease of bone marrow repopulation. 6. The exposure to &apos;strange&apos; radiation can bring about an increase in the proportion of neutrophils in the peripheral blood of experimental animals. 7. It can be suggested by the results of the test exposures that &apos;strange&apos; radiation can affect human health. 8. It has been shown by these preliminary studies that in order to gain an insight into the biological effects of &apos;strange&apos; radiation further investigation would be necessary. (authors)

  14. Serum 3,3&apos;-L-diiodothyronine, a direct radioimmunoassay in human serum: method and clinical results. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Burger, A.; Sakoloff, C.


    A specific radioimmunoassay for 3,3&apos;-diiodothyronine (T/sub 2/) is described which is capable of detecting as little as 1.3 ng/dl. The antiserum recognizes mainly T/sub 2/; biliary conjugates of T/sub 2/ bind slightly to the antibody. The intraassay and interassay coefficients of variation were, respectively, 5.7% and 13.1%. T/sub 2/ was detected in the serum of hypothyroid patients treated with triiodothyronine (T/sub 3/) and in euthyroid subjects treated with reverse triiodothyronine (rT/sub 3/). These results suggest that both T/sub 3/ and rT/sub 3/ are deiodinated to T/sub 2/. Serum concentrations of T/sub 2/ in normal subjects decreased with age. Between 20 and 40 years the mean concentration was 4.3 +- 2.0 ng/dl (2 SD), between 41 and 60 years it varied from 1.9 to 5.8 ng/dl (3.8 +- 0.3 ng/dl, SE) and in elderly subjects have 60 years concentrations varied from unmeasurable to 4 ng/dl (2.9 +- 0.4 ng/dl, SE). Low serum T/sub 2/ concentrations were found in anorexia nervosa (2.5 +- 0.3 ng/dl, SE). In hypothyroidism the serum concentrations were low or unmeasurable. As most of the hypothyroid subjects were elderly their serum T/sub 2/ concentrations overlapped with the low values found in the elderly euthyroid subjects. In classical hyperthyroidism serum T/sub 2/ concentrations were greatly increased (3.3 to 31 ng/dl (11.8 +- 2.7 ng/dl, SE) but in &apos;&apos;T/sub 3/ toxicosis&apos;&apos; the concentrations were only modestly increased (2.4 to 8.8 ng/dl, 5.2 +- 0.8 ng/dl, SE).

  15. Chamber transport of &apos;'foot'&apos; pulses for heavy-ion fusion

    Energy Technology Data Exchange (ETDEWEB)

    Sharp, W.M.; Callahan-Miller, D.A.; Tabak, M.; Yu, S.S.; Peterson, P.F.


    Indirect-drive targets for heavy-ion fusion must initially be heated by &apos;'foot'&apos; pulses that precede the main heating pulses by tens of nanoseconds. These pulses typically have a lower energy and perveance than the main pulses, and the fusion-chamber environment is different from that seen by later pulses. The preliminary particle-in-cell simulations of foot pulses here examine the sensitivity of the beam focusing to ion-beam perveance, background-gas density, and pre-neutralization by a plasma near the chamber entry port.

  16. Coral bleaching and ocean &apos;&apos;hot spots&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Goreau, T.J. (Global Coral Reef Alliance, Chappaqua, NY (United States)); Hayes, R.L. (Howard Univ., Washington, DC (United States). College of Medicine)


    Global sea-surface temperature maps show that mass coral-reef bleaching episodes between 1983 and 1991 followed positive anomalies more than 1 deg C above long-term monthly averages (&apos;&apos;hot spots&apos;&apos;) during the preceding warm season. Irregular formation, movement, and disappearance of hot spots make their detailed long-term prediction impossible, but they can be tracked in real time from satellite data. Monitoring of ocean hot spots and of coral bleaching is needed if the Framework Convention of Climate Change is to meet its goal of protecting the most temperature sensitive ecosystems. 47 refs, 3 figs

  17. Improved Security Via &apos;&apos;Town Crier&apos;&apos; Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, R. G.; Garcia, A. R. E.; Pacheco, A. N.


    Waste managers are increasingly expected to provide good security for the hazardous materials they marshal. Good security requires, among other things, effective tamper and intrusion detection. We have developed and demonstrated a new method for tamper and intrusion detection which we call the &apos;&apos;town crier method&apos;&apos;. It avoids many of the problems and vulnerabilities associated with traditional approaches, and has significant advantages for hazardous waste transport. We constructed two rudimentary town crier prototype systems, and tested them for monitoring cargo inside a truck. Preliminary results are encouraging.

  18. Heavy cluster decay of trans-zirconium &apos;'stable'&apos; nuclides

    Energy Technology Data Exchange (ETDEWEB)

    Poenaru, D.N.; Greiner, W.; Ivascu, M.; Sandulescu, A.


    By using the analytical superasymmetric fission model it is shown that all &apos;'stable'&apos; nuclei lighter than lead with Z>40 are metastable relative to the spontaneous emission of nuclear clusters. An even-odd effect is included in the zero point vibration energy. Half-lives in the range 10/sup 40/--10/sup 50/ s are obtained for Z>62. The region of metastability against these new decay modes is extended beyond that for ..cap alpha.. decay and in some cases, in the competing region, the emission rates for nuclear clusters are larger than for ..cap alpha.. decay.

  19. The role of &apos;&apos;momentum removal&apos;&apos; in divertor detachment

    Energy Technology Data Exchange (ETDEWEB)

    Kukushkin, A.S. [Kurchatov Institute, Moscow (Russian Federation); NRNU MEPhI, Moscow (Russian Federation); Pacher, H.D. [INRS-EMT, Varennes, Quebec (Canada)


    The role of &apos;&apos;momentum removal&apos;&apos; (the drag force on the plasma ion flow) in divertor detachment is considered and analysed in detail. This analysis of the 2D modelling results shows that the drag force cannot reduce the power and particle flux to the target directly. However, it is essential for creating the conditions for efficient radiation and volumetric plasma recombination, which in turn do the job. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  20. Improved Security Via &apos;&apos;Town Crier&apos;&apos; Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, R. G.; Garcia, A. R. E.; Pacheco, A. N.


    Waste managers are increasingly expected to provide good security for the hazardous materials they marshal. Good security requires, among other things, effective tamper and intrusion detection. We have developed and demonstrated a new method for tamper and intrusion detection which we call the &apos;&apos;town crier method&apos;&apos;. It avoids many of the problems and vulnerabilities associated with traditional approaches, and has significant advantages for hazardous waste transport. We constructed two rudimentary town crier prototype systems, and tested them for monitoring cargo inside a truck. Preliminary results are encouraging.

  1. Overproduction of a kinetic subclass of VLDL-apoB, and direct catabolism of VLDL-apoB in human endogenous hypertriglyceridemia: an analytical model solution of tracer data

    Energy Technology Data Exchange (ETDEWEB)

    Eaton, R.P.; Allen, R.C.; Schade, D.S.


    To investigate the participation of the major apoprotein involved in triglyceride transport in the pathogenesis of endogenous hypertriglyceridemia, five kinetic studies of apoprotein B were conducted in volunteer normolipidemic subjects and six studies in four patients with endogenous hypertriglyceridemia. The transport of apoprotein B within four kinetic subclasses of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) was studied by injection of (/sup 75/Se)selenomethionine. A 24-fold increase in the entry of newly synthesized apoprotein B at the initial kinetic subclass of the four-compartment VLDL delipidation sequence characterized the hypertriglyceridemic studies relative to normal subjects. Moreover, approximately 75 mg/kg per day of VLDL-B turnover reflected direct catabolism independent of conversion to IDL and/or to LDL, in contrast to the 8 mg/kg per day observed in controls. IDL-B was derived from VLDL-B in both normal and hypertriglyceridemic subjects, and was responsible for greater than 70% of all LDL-B synthesis. LDL-B pool size and turnover were indistinguishable in hypertriglyceridemic subjects from that observed in normal subjects. These studies suggest that two kinetic phenomena may characterize the pathophysiology of endogenous hypertriglyceridemia: a) over-production of apoB within a kinetic subclass of VLDL and b) preferential catabolism of hypertriglyceridemic VLDL without prior conversion to IDL/LDL.

  2. Agreement &apos;&apos;power networks and environment&apos;&apos; 2001-2003; Accord &apos;&apos;reseaux electriques et environnement&apos;&apos; 2001-2003

    Energy Technology Data Exchange (ETDEWEB)



    This agreement, discussed between the French government and Electricite de France (EdF) group, proposes some engagements for the 2001-2003 era for a better environmental integration of power transmission and distribution networks. The agreement is made of two parts: 1 - public distribution networks: realization of new workmanship (medium and low voltage power lines, new lines in dense urban areas), actions on existing workmanship (consequences of December 1999 storms, aesthetical aspects, burial of the main overhead lines in wooded areas, reinforcement of EdF&apos;s environmental commitment, remedial actions for environmental &apos;black points&apos;), general measures of implementation (increasing network safety, protection of birds fauna, coordination of works); 2 - public transportation network (RTE): development and safety improvement of the public transportation network (reinforced arrangement for the establishment of regional development schemes, development of international interconnections, safety improvement of the public transportation network, RTE&apos;s environmental plan); line projects (arrangements during projects elaboration, accompanying program); long lived RTE&apos;s commitment (environmental management and ISO-14001 certification, vigilance with respect to electromagnetic fields, R and D). (J.S.)

  3. Do we need a &apos;&apos;green medicine&apos;&apos;?; Brauchen wir &apos;&apos;Gruene Medizin?&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, M.; Daschner, F.; Scherrer, M. [Universitaetsklinikum Freiburg (Germany)


    Spontaneously, we do associate &apos;&apos;green medicine&apos;&apos; with terms like naturopathy, natural healing substances, herbal active agents, homeopathy, healthy food, preventive medicine and similar things, and finally we think of ecology. This is the focus of the following article. First of all, the following question arises: Are there any environment-friendly and cost-saving alternatives to the present medicine? There is an increasing number of environment-caused diseases. Therefore, a medicine not coping with the environment is not credible. In today&apos;s medicine, for example, there are too many persistent detergents, water-polluting disinfectants, and many disposable materials. Too much water ist consumed, whereas the use of renewable energies is only limited. And too little natural healing methods are applied in diagnostics and therapy. Presently, in Germany, 16,7 million in-patients are treated in Germany, 1,16 million out-patients have surgeries in 2166 hospitals by ca. 1,1 million medical staff. All this work needs energy and materials which bring various risks to environment and the patients. During the last two decades, however, many efforts were made in the field of environment protection in medicine. There is hardly a hospital left which has not taken measures of protecting the environment. In the branch-specific quality management system KTQ (=cooperation for transparency and quality in the health system). environment protection measures are interrogated and systematically assessed.

  4. Focus on &apos;&apos;regulation management&apos;&apos;. Information material - documentation; Brennpunkt &apos;'Regulierungsmanagement'&apos;. Materialienband

    Energy Technology Data Exchange (ETDEWEB)



    With the new Energy Economy Act coming into force and regulation authorities being established, the public utilities providing gas and electricity are starting the implementation of regulation. This creates a new field of activity: The regulation management. The regulation manager in a public utility has a wide field of functions. He or she is responsible for the organisation of the enterprise with regard to the regulation authority. He must coordinate various divisions of the enterprise taking into consideration the interest of the regulation authority and take steps to form a common understanding. The meeting called &apos;&apos;Focus on Regulation Management&apos;&apos; provides an insight into the most important tasks of a regulation manager, giving information useful for establishing an efficient regulation management system. In the first part of the meeting, the basics and tasks of regulation management and the legal protection towards the regulation authorities are dealt with. Furthermore, the president of the states&apos; committee in the BNetzA, Mr. Peter Franke, will introduce the present fields of activity, reporting about first experiences gained with the network cost requests. In the second part, practitioners from the enterprises report about their experiences with the implementation of regulation management. This includes especially data management, an effective reporting system and the implementation of a relationship management between the regulation authority and the enterprise. The meeting closes with a speech on the subject of comparing methods and benchmarking in the network.


    Energy Technology Data Exchange (ETDEWEB)

    Karlin, Yurii; Dmitriev, Sergey; Iljin, Vadim; Ojovan, Mihail; Burcl, Rudolf


    Mobile modular installation &apos;'Aqua-Express'&apos; is a liquid low level and intermediate level radioactive waste (LL&ILRW) treatment facility, intended for not large research centers and other organizations, which activity causes the formation of a few quantity (up to 500 m3/year) of low and intermediate level radioactive waste water. Mobile modular installation &apos;'Aqua-Express'&apos; has the following features: (1) filtration, sorption and ultrafiltration units are used for LL&ILRW purification; (2) installation &apos;'Aqua-Express'&apos; consists of a cascade of three autonomous aqueous liquid waste-purifying installations; (3) installation &apos;'Aqua-Express'&apos; is a mobile installation; the installation can be transported by car, train, ship, or plane, as well as placed in a standard transport (sea or railway) container; (4) installation &apos;'Aqua-Express'&apos; does not includes any technological equipment for conditioning the secondary radioactive waste. Productivity of the installation &apos;'Aqua-Express'&apos; by purified water depends on composition of the initial liquid waste and makes up to 300 l/h. In present report is described the design of installation &apos;'Aqua-Express'&apos;, theory of LRW purification in the installation &apos;'Aqua-Express'&apos; and some results of its use at cleaning real radioactive waters at State unitary enterprise - MosNPO &apos;'Radon'&apos;.

  6. Nuclear waste disposal. A wicked and highly conflict bearing societal problem; Nukleare Entsorgung. Ein &apos;'wicked'&apos; und hoechst konfliktbehaftetes Gesellschaftsproblem

    Energy Technology Data Exchange (ETDEWEB)

    Brunnengraeber, Achim; Mez, Lutz [Freie Univ. Berlin (Germany). Forschungszentrum fuer Umweltpolitik; Di Nucci, Maria Rosaria; Schreuers, Miranda [Freie Univ. Berlin (Germany)


    The final disposal of nuclear wastes is called &apos;'messy'&apos; or &apos;'wicked'&apos; in the political science literature. The highly complicated problems are characterized by a number of features such as intra- and inter-generational aspects and ethical questions. In the case of stakeholders the differences concern ideologies, interests, merits and preferences that cause conflicts. The search for solutions is complicated due to interacting political, social, ecologic, economic and technical aspects. The concepts &apos;&apos;wicked problems&apos;&apos; and &apos;'multi-level-governance'&apos; are promising approaches to solve the complicated situation.

  7. ApoM: gene regulation and effects on HDL metabolism

    DEFF Research Database (Denmark)

    Nielsen, Lars B; Christoffersen, Christina; Ahnström, Josefin;


    The recently discovered apolipoprotein M (apoM) is a plasma protein of the lipocalin family associated with the lipoproteins (mainly high-density lipoproteins, or HDLs). Expression of the apoM gene in the liver is regulated by transcription factors that control key steps in hepatic lipid and gluc......The recently discovered apolipoprotein M (apoM) is a plasma protein of the lipocalin family associated with the lipoproteins (mainly high-density lipoproteins, or HDLs). Expression of the apoM gene in the liver is regulated by transcription factors that control key steps in hepatic lipid...... changes in HDLs, and overexpression of the apoM gene reduced atherosclerosis. In conclusion, it seems that apoM plays a part in lipoprotein metabolism; however, the biological impact of apoM in humans remains to be determined....

  8. Performance of &apos;'ductless'&apos; personalized ventilation in conjunction with displacement ventilation: Impact of intake height

    Energy Technology Data Exchange (ETDEWEB)

    Halvonova, Barbora [Department of Building Services, Slovak University of Technology in Bratislava, 813 68 Bratislava (Slovakia); International Centre for Indoor Environment and Energy, Department of Civil Engineering, Technical University of Denmark (Denmark); Melikov, Arsen K. [International Centre for Indoor Environment and Energy, Department of Civil Engineering, Technical University of Denmark (Denmark)


    The importance of the intake positioning height above the floor level on the performance of &apos;'ductless'&apos; personalized ventilation (&apos;'ductless'&apos; PV) in conjunction with displacement ventilation (DV) was examined with regard to the quality of inhaled air and of the thermal comfort provided. A typical office room with two workstations positioned one behind the other was arranged in a full-scale room. Each workstation consisted of a table with an installed &apos;'ductless'&apos; PV system, PC, desk lamp and seated breathing thermal manikin. The &apos;'ductless'&apos; PV system sucked the clean and cool displacement air supplied over the floor at four different heights, i.e. 2, 5, 10 and 20 cm and transported it direct to the breathing level. Moreover, two displacement airflow rates were used with a supply temperature adjusted in order to maintain an exhaust air temperature of 26 C. Two pollution sources, namely air exhaled by one of the manikins and passive pollution on the table in front of the same manikin were simulated by constant dosing of tracer gases. The results show that the positioning of a &apos;'ductless'&apos; PV intake height up to 0.2 m above the floor will not significantly influence the quality of inhaled air and thermal comfort. (author)

  9. &apos;&apos;Measuring the Costs of Climate Change Policies&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Montgomery, W. D.; Smith, A. E.; Biggar, S. L.; Bernstein, P.M.


    Studies of the costs of climate change policies have utilized a variety of measures or metrics for summarizing costs. The leading economic models have utilized GNP, GDP, the &apos;&apos;area under a marginal cost curve,&apos;&apos; the discounted present value of consumption, and a welfare measure taken directly from the utility function of the model&apos;s representative agent (the &apos;&apos;Equivalent Variation&apos;&apos;). Even when calculated using a single model, these metrics do not necessarily give similar magnitudes of costs or even rank policies consistently. This paper discusses in non-technical terms the economic concepts lying behind each concept, the theoretical basis for expecting each measure to provide a consistent ranking of policies, and the reasons why different measures provide different rankings. It identifies a method of calculating the &apos;&apos;Equivalent Variation&apos;&apos; as theoretically superior to the other cost metrics in ranking policies. When regulators put forward new economic or regulatory policies, there is a need to compare the costs and benefits of these new policies to existing policies and other alternatives to determine which policy is most cost-effective. For command and control policies, it is quite difficult to compute costs, but for more market-based policies, economists have had a great deal of success employing general equilibrium models to assess a policy&apos;s costs. Not all cost measures, however, arrive at the same ranking. Furthermore, cost measures can produce contradictory results for a specific policy. These problems make it difficult for a policy-maker to determine the best policy. For a cost measures to be of value, one would like to be confident of two things. First one wants to be sure whether the policy is a winner or loser. Second, one wants to be confident that a measure produces the correct policy ranking. That is, one wants to have confidence in a policy measure&apos;s ability to correctly rank

  10. Development of emergency response training program based on human factors; Developpement d&apos;un programme de formation pour la reaction aux situations d&apos;urgences base sur les facteurs humains

    Energy Technology Data Exchange (ETDEWEB)

    Nakata, Y. [Osaka Gas Co., Ltd. (Japan)


    A training program has been developed at Osaka Gas Co., Ltd. to improve personal response to emergency situations by enabling plant shift chiefs to understand the unique human behavioral patterns that appear during emergencies. The program provides comprehensive and systematic training consisting of lectures and seminars based on a Human Factor Handbook, simulation training, and feedback training. The program can also be applied to all areas of the process industry. (author)

  11. Development of emergency response training program based on human factors; Developpement d&apos;un programme de formation pour la reaction aux situations d&apos;urgences base sur les facteurs humains

    Energy Technology Data Exchange (ETDEWEB)

    Nakata, Y. [Osaka Gas Co., Ltd. (Japan)


    A training program has been developed at Osaka Gas Co., Ltd. to improve personal response to emergency situations by enabling plant shift chiefs to understand the unique human behavioral patterns that appear during emergencies. The program provides comprehensive and systematic training consisting of lectures and seminars based on a Human Factor Handbook, simulation training, and feedback training. The program can also be applied to all areas of the process industry. (author)

  12. Radioimmunoassay for guanosin-5&apos;-diphosphate-3&apos;-diphosphate and adenosine-5&apos;-triphosphate-3&apos;-diphosphate

    Energy Technology Data Exchange (ETDEWEB)

    Hamagishi, Y.; Oki, T.; Tone, H.; Inui, T. (Sanraku-Ocean Co. Ltd., Fujisawa, Kanagawa (Japan). Central Research Lab.)


    A radioimmunoassay for guanosine-5&apos;-diphosphate-3&apos;-diphosphate (ppGpp) and adenosine-5&apos;-triphosphate-3&apos;-diphosphate (pppApp) has been developed. The assay method is based on competition of an unlabeled highly phosphorylated nucleotide with /sup 3/H-labeled highly phosphorylated nucleotide for binding sites on a specific antibody. Antibodies to ppGpp and pppApp were obtained by immunizing rabbits with the antigen prepared by conjugating ppGpp with human serum albumin using 1-ethyl-3-(3-dimethylaminoprophyl)carbodiimide, and with the antigen prepared by conjugating 8-(6-aminohexyl)amino-adenosine-5&apos;-triphosphate-3&apos;-diphosphate with human serum albumin using glutaraldehyde, respectively. Antibody-bound /sup 3/H-labeled highly phosphorylated nucleotides were separated from the free /sup 3/H-labeled highly phosphorylated nucleotides by selective adsorption on dextran-coated charcoal. Displacement plots were linear over a concentration range of 5 - 1,000 pmol/assay tube in a log-probit percentage plot. Application of this method to biological systems offers improved accuracy and convenience compared with the previous /sup 32/PO/sub 4/-labeling technique.

  13. &apos;Teleparallel&apos; dark energy

    Energy Technology Data Exchange (ETDEWEB)

    Geng, Chao-Qiang, E-mail: [Department of Physics, National Tsing Hua University, Hsinchu 300, Taiwan (China); National Center for Theoretical Sciences, Hsinchu 300, Taiwan (China); Lee, Chung-Chi, E-mail: [Department of Physics, National Tsing Hua University, Hsinchu 300, Taiwan (China); Saridakis, Emmanuel N., E-mail: [CASPER, Physics Department, Baylor University, Waco, TX 76798-7310 (United States); National Center for Theoretical Sciences, Hsinchu 300, Taiwan (China); Wu, Yi-Peng, E-mail: [Department of Physics, National Tsing Hua University, Hsinchu 300, Taiwan (China)


    Using the &apos;teleparallel&apos; equivalent of General Relativity as the gravitational sector, which is based on torsion instead of curvature, we add a canonical scalar field, allowing for a nonminimal coupling with gravity. Although the minimal case is completely equivalent to standard quintessence, the nonminimal scenario has a richer structure, exhibiting quintessence-like or phantom-like behavior, or experiencing the phantom-divide crossing. The richer structure is manifested in the absence of a conformal transformation to an equivalent minimally-coupled model.

  14. Artificial intelligence: Human effects

    Energy Technology Data Exchange (ETDEWEB)

    Yazdani, M.; Narayanan, A.


    This book presents an up-to-date study of the interaction between the fast-growing discipline of artificial intelligence and other human endeavors. The volume explores the scope and limitations of computing, and presents a history of the debate on the possibility of machines achieving intelligence. The authors offer a state-of-the-art survey of Al, concentrating on the &apos;'mind'&apos; (language understanding) and the &apos;'body'&apos; (robotics) of intelligent computing systems.

  15. Etiology and implications of dense cavitary &apos;'photopenia'&apos; on myocardial perfusion scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Dae, M.; Canhasi, B.; Botvinick, E.; Olvera, S.; Schechtmann, N.; Engelstad, B.; Hattner, R.; Schiller, N.; O' Connell, W.; Faulkner, D.


    Dense cavitary &apos;'photopenia'&apos; was observed on 21 of 200 consecutive stress perfusion scintigrams. A prominent finding in many cases, it sometimes occupied only a portion of the region overlying the ventricular cavity, was often seen in some projections and not others, and was frequently adjacent to myocardial perfusion defects. To distinguish an etiology among reduced cavitary radioactivity, relatively increased background radioactivity, or reduced radioactivity in overlying myocardium, quantitative analysis of cavitary, lung and myocardial radioactivity was performed in patients with dense cavitary &apos;'photopenia,'&apos; with and without lung uptake, and compared with results from studies showing increased lung uptake without cavitary photopenia and with normal studies. The results showed that dense cavitary photopenia was related to reduced radioactivity in overlying myocardium. Correlative imaging studies performed with echocardiography and contrast ventriculography confirmed this relationship to myocardial scar in 15 of 21 patients in whom associated akinesis or dyskinesis was seen. Hence, dense cavitary photopenia on stress perfusion scintigraphy is due to a dense myocardial perfusion abnormality, and is often indicative of related scar and an associated severe contraction abnormality.

  16. Considerations about the apparent &apos;&apos;superluminal expansions&apos;&apos; observed in astrophysics

    Energy Technology Data Exchange (ETDEWEB)

    Recami, E.; Castellino, A.; Maccarrone, G.D.; Rodono, M.


    The orthodox models devised to explain the apparent &apos;&apos;superluminal expansions&apos;&apos; observed in astrophysics - and here briefly summarized and discussed together with the experimental data - do not seem to be too much successful, especially when confronted with the most recent observations, suggesting complicated expansion patterns, even with possible accelerations. At this point it may be, therefore, of some interest to explore the possible alternative models in which actual Superluminal motions take place. To prepare the ground, we start from a variational principle, introduce the elements of a tachyon mechanics within special relativity, and argue about the expected behaviour of tachyonic objects when interacting (gravitationally, for instance) among themselves or with ordinary matter. We then review and develop the simplet &apos;&apos;Superluminal models&apos;&apos;, paying particular attention to the observations which they would give rise to. We conclude that some of them appear to be physically acceptable and are statistically favoured with respect to the orthodox ones.

  17. Centre for urban ecotechnology in &apos;'Oeksnehallen'&apos;. [Copenhagen, Denmark

    Energy Technology Data Exchange (ETDEWEB)


    The Lord Mayor&apos;s Department of the municipality of Copenhagen, Denmark, has with support from this project made a proposal for the establishment of the Centre for Urban Ecotechnology in &apos;'Oeksnehallen'&apos;, located in the Vesterbro area of the city. The centre should contribute to the dissemination of knowledge on ecological techniques (regarding passive solar energy etc.) to the inhabitants of Vesterbro and other citizens of Copenhagen, and also serve as a centre in an European context. The ecological demonstration centre will cover an area of two thousand square meters and will also include a cafe, a room for showing coloured slides, facilities for exhibitions created by the center and interested firms etc. The centre should play an important role as part of the ecological concept of urban renewal in Vesterbro. (author).

  18. Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription

    Directory of Open Access Journals (Sweden)

    Bin Hong


    Full Text Available Apolipoprotein A-I (Apo A-I is the principal protein component of high density lipoprotein (HDL, which is generally considered as a potential therapeutic target against atherosclerosis. The understanding of the Apo A-I regulation mechanism has fuelled the development of novel HDL targeted therapeutic approaches. To identify novel agents that can upregulate Apo A-I expression, we performed a cell-based reporter assay to screen 25,600 small molecules. Based on the dataset obtained from screening, a series of novel analogs of substituted benzamides containing azaspiro rings were assessed for their ability to induce the transcription of the Apo A-I gene, and the structure-activity relationship (SAR around these analogs was also proposed. The results indicated that the trifluoromethyl substituted benzamide containing an azaspiro ring is a promising backbone for designing Apo A-I transcriptional upregulator and could be viable leads for development of new drugs to prevent and treat atherosclerosis in the future.

  19. Preparation of data relevant to &apos;&apos;Equivalent Uniform Burnup&apos;&apos; and Equivalent Initial Enrichment&apos;&apos; for burnup credit evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Yasushi; Okuno, Hiroshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Murazaki, Minoru [Tokyo Nuclear Service Inc., Tokyo (Japan)


    Based on the PWR spent fuel composition data measured at JAERI, two kinds of simplified methods such as &apos;&apos;Equivalent Uniform Burnup&apos;&apos; and &apos;&apos;Equivalent Initial Enrichment&apos;&apos; have been introduced. And relevant evaluation curves have been prepared for criticality safety evaluation of spent fuel storage pool and transport casks, taking burnup of spent fuel into consideration. These simplified methods can be used to obtain an effective neutron multiplication factor for a spent fuel storage/transportation system by using the ORIGEN2.1 burnup code and the KENO-Va criticality code without considering axial burnup profile in spent fuel and other various factors introducing calculated errors. &apos;&apos;Equivalent Uniform Burnup&apos;&apos; is set up for its criticality analysis to be reactivity equivalent with the detailed analysis, in which the experimentally obtained isotopic composition together with a typical axial burnup profile and various factors such as irradiation history are considered on the conservative side. On the other hand, Equivalent Initial Enrichment&apos;&apos; is set up for its criticality analysis to be reactivity equivalent with the detailed analysis such as above when it is used in the so called fresh fuel assumption. (author)

  20. &apos;&apos;After the Genome 5 Conference&apos;&apos; to be held October 6-10, 1999 in Jackson Hole, Wyoming

    Energy Technology Data Exchange (ETDEWEB)

    Roger Brent


    OAK B139 The postgenomic era is arriving faster than anyone had imagined--sometime during 2000 we&apos;ll have a large fraction of the human genome sequence. Heretofore, our understanding of function has come from non-industrial experiments whose conclusions were largely framed in human language. The advent of large amounts of sequence data, and of &apos;&apos;functional genomic&apos;&apos; data types such as mRNA expression data, have changed this picture. These data share the feature that individual observations and measurements are typically relatively low value adding. Such data is now being generated so rapidly that the amount of information contained in it will surpass the amount of biological information collected by traditional means. It is tantalizing to envision using genomic information to create a quantitative biology with a very strong data component. Unfortunately, we are very early in our understanding of how to &apos;&apos;compute on&apos;&apos; genomic information so as to extract biological knowledge from i t. In fact, some current efforts to come to grips with genomic information often resemble a computer savvy library science, where the most important issues concern categories, classification schemes, and information retrieval. When exploring new libraries, a measure of cataloging and inventory is surely inevitable. However, at some point we will need to move from library science to scholarship.We would like to achieve a quantitative and predictive understanding of biological function. We realize that making the bridge from knowledge of systems to the sets of abstractions that constitute computable entities is not easy. The After the Genome meetings were started in 1995 to help the biological community think about and prepare for the changes in biological research in the face of the oncoming flow of genomic information. The term &apos;&apos;After the Genome&apos;&apos; refers to a future in which complete inventories of the gene products of

  1. &apos;'VaneCAM'&apos; - the third generation of camshaft adjustment systems; &apos;'VaneCAM'&apos; - Nockenwellenversteller der dritten Generation

    Energy Technology Data Exchange (ETDEWEB)

    Knecht, A. [Hydraulik-Ring GmbH, Nuertingen (Germany). Entwicklung Motorentechnik; Stephan, W. [Hydraulik-Ring GmbH, Nuertingen (Germany); Hannibal, W. [Fachhochschule Suedwestfalen, Iserlohn (Germany). Labor fuer Konstruktion und CAE-Anwendungen


    Continuously variable camphasers are now well established for modern spark-ignition engines in high-volume production. With the latest generation of camshaft adjustment systems using the vane-type actuator principle, it is possible to move rapidly and reliably through a large adjustment angle. The layout of these adjusting systems is very simple. The production costs are low in comparison to the first generation of camphasers using spur/helical gears to vary the valve timing. The new-generation systems are mechatronic, with the function depending on the coordination and tuning of hydraulic actuation and engine electronics. The term &apos;VaneCAM&apos; is used for the continuously variable systems of this new generation supplied by Hydraulik-Ring in Nuertingen, Germany. (orig.) [German] Stufenlos wirkende Nockenwellenversteller haben sich an modernen Ottomotoren in den letzten Jahren in der Grossserie etabliert. Mit der neuesten Generation von Nockenwellenverstellern, die nach dem Schwenkmotor-Prinzip aufgebaut sind, lassen sich grosse Verdrehwinkel sehr schnell und betriebssicher verstellen. Der Aufbau dieser Versteller ist einfach, und die Herstellkosten sind gering im Vergleich zur ersten Generation von Verstellern. Bei den Systemen der neuen Generation handelt es sich um mechatronische Systeme, deren Funktion von dem Zusammenspiel und der Abstimmung von hydraulischer Ansteuerung und Motorelektronik abhaengt. Mit dem Begriff &apos;VaneCAM&apos; werden die stufenlos wirkenden Systeme dieser neuen Generation von Hydraulik-Ring aus Nuertingen bezeichnet. (orig.)

  2. Production of intermediate vector meson resonances in the process {tau}{yields}{pi}&apos;'{+-}{pi}'&apos;0{nu}

    Energy Technology Data Exchange (ETDEWEB)

    Casaus, J.; Mana, C.


    We present a study on the invariant mass distribution of {pi}&apos;'{+-}{pi}'&apos;0 pairs produced in the process {tau}{yields}{pi}&apos;'{+-}{pi}'&apos;0{nu} . The analysis is based on a sample of 33,096 events collected by the L3 detector between 1991 and 1994. The data is not inconsistent with the hypothesis that the process is being mediated by the p(770) meson alone but is in better agreement with the inclusion of an extra {rho} resonance in the decay of the tau lepton. (Author) 10 refs.

  3. Comments on &apos;&apos;Introduction to the chemistry of fractionally charged atoms: Electronegativity&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Liebman, J.F.; Huheey, J.E.


    A comparison is made between the electronegativities of &apos;&apos;quark atoms&apos;&apos; as predicted by a recent article, and those suggested by traditional chemical methods. It is shown that the neglect of valence-state considerations for the ionization energies and electron affinities produces serious errors in calculating electronegativities by the Mulliken method. As analyses of the values for &apos;&apos;normal atoms&apos;&apos; show such disparities, it is likely that the new numbers are in error.

  4. Novel action of apolipoprotein E (ApoE: ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons

    Directory of Open Access Journals (Sweden)

    Fujita Shinobu C


    Full Text Available Abstract Background Since the majority of apolipoprotein E (apoE existing in the cerebrospinal fluid is associated with high-density lipoprotein (HDL, one should focus on the role of the apoE-HDL complex rather than on that of free apoE in cholesterol metabolism in the central nervous system. However, the apoE-isoform-specific effect of apoE-HDL on cholesterol transport remains unclarified. Results Here we show that apoE3-HDL induced a marked cholesterol release from neurons, while apoE4-HDL induced little. To elucidate the mechanism underlying this phenomenon, we used a complex of lipid emulsion (EM with recombinant apoE3 or apoE4 (apoE-EM at various apoE concentrations. When a small number of apoE molecules were associated with EM, apoE3- and apoE4-EM, induced a marked cholesterol release to a level similar to that induced by EM alone. However, when apoE at given concentrations was incubated with EM, apoE3-EM induced a marked cholesterol release, while apoE4-EM induced little. Under these conditions, a greater number of apoE4 molecules were associated with EM than apoE3 molecules. When an increasing number of apoE molecules were associated with EM, both apoE3-EM and apoE4-EM induced little cholesterol release. Preincubation with β-mercaptoethanol increased the number of apoE3 molecules associated with EM similar to that of apoE4 molecules, indicating that the presence (apoE3 or absence (apoE4 of intermolecular disulfide bond formation is responsible for the association of a greater number of apoE4 molecules to EM than apoE3 molecules. Conclusion These results suggest that although apoE and a lipid particle are lipid acceptors, when apoE and a lipid particle form a complex, apoE on the particle surface inhibits the lipid particle-mediated cholesterol release from cells in an apoE-concentration-dependent manner.

  5. Light ions radiobiological effects on human tumoral cells: measurements modelling and application to hadron-therapy; Mesures et modelisation des effets radiobiologiques des ions legers sur des cellules tumorales humaines: application a l&apos;hadrontherapie

    Energy Technology Data Exchange (ETDEWEB)

    Jalade, P


    In classical radiotherapy, the characteristics of photons interactions undergo limits for the treatment of radioresistant and not well located tumours. Pioneering treatments of patients at the Lawrence Laboratory at Berkeley has demonstrated two advantages of hadrons beams: the Relative Biologic Effect (the RBE) and the ballistic of the beams. Since 1994, the clinical centre at Chiba, has demonstrated successfully the applicability of the method. A physics group, managed by G. Kraft, at Darmstadt in Germany, has underlined the advantages of carbon beams. An European pool, called ENGIGHT (European Network for LIGHt ion Therapy) has been created in which the French ETOILE project appeared. The purpose of the thesis concerns measurements and models of &apos;in vitro&apos; human cells survival. In the first part, the nowadays situation in particles interactions, tracks and cells structures and radiobiology is presented here. The second is devoted to the models based on the beam tracks and localization of the physical dose. Discussion of sensitivity to various parameters of the model has been realized with the help of numerical simulations. Finally the predictions of the improved model has been compared to experimental irradiations of human cells with argon and carbon beams of the GANIL machine. Conclusion of such study shows the performance and limits of a local model for predicting the radiobiological efficiency of light ions in hadron-therapy. (author)

  6. Orbit as a Mirror of Systemic Disease; &apos;&apos; Epidemiologic, Clinical and Imaging &apos;&apos;

    Directory of Open Access Journals (Sweden)

    Aliakbar Ameri


    Full Text Available   "n1- Infectious: toxoplasmosis , toxocariasis ,TB , syphilis , leprosy , HIV , CMV. "n2- Non infectous: endocrine, diabetes, thyroid, connective tissue disease &apos;&apos;RA, SLE, wegeners, PAN, systemic sclerosis&apos;&apos;, vasculitides, GCA&apos;&apos;, sarcoidosis, behcet&apos;s disease, vogt koyangi harada syndrome, phakomatoses. "nAll diseases should be demonstrated by clinical images and imaging slides. "n-imaging "nX-RAY, high frequency US and color doppler, 2D and 3D X-RAY CT, MRI: "n1- X-RAY: in fractures, foreign bodies, skull combined anomalies and few other cases. "n2-High-frequency ultrasound for posterior chamber and ciliary body micro-anatomic changes &apos;&apos; tumors granulations&apos;&apos;. "nColor Doppler study for vascular lesions, central retin artery, tumors in the globe and retrobulbar region. "n3- X-RAY CT for tumors, 2D and 3D for fractures, 3D for bone anatomy, foreign body &apos;&apos; modality of choice is 2directional 2D CT scan &apos;&apos;, sino-nasal diseases, CT-angiography or phlebography in large vessel evaluation, DSA for small vessel anatomy. "n4- MRI for tumors and infection also granulation process. "nMRI and MRV in large vessel anatomy, functional – MRI for the visual pathway, tractography. "nConclusion : "nModality of choice : "n1- CT for foreign bodies &apos;&apos; MRI is contra-indicated in the first step specially in metallic fragments &apos;&apos;. CT for micro-calcification &apos;&apos; retinoblastoma &apos;&apos;,CT for fractures. "n2- MRI for tumors, biometry, soft tissue disease and functional imaging. "n3- DSA for vascular disease of the eye. "n4- U.S for biometery, posterior Chamber, iris and ciliary body lesions. 5- Fluorescein angiography for the retina.  

  7. Changes of lymphocyte subsets after local irradiation for early stage breast cancer and seminoma testis: long-term increase of activated (HLA-DR+) T-cells and decrease of &apos;'naive'&apos; (CD4-CD45R) T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    De Ruysscher, D.; Aerts, R.; Vantongelen, K.; Schueren, E. van der (University Hospital, Leuven (Belgium). Dept. of Radiotherapy and Oncology); Waer, M.; Vandeputte, M. (Rega Inst. of Medical Research, Leuven (Belgium). Div. of Immunopathology)


    Blood lymphocyte subsets of early breast cancer patients and of men with stage I seminoma of the testis were studied up to 6 years after radiotherapy. Similar results were obtained in the two patient groups. After a temporary decrease, the CD4-w29 or &apos;'memory'&apos; T cells recovered completely, while the CD4-45R or &apos;'naive'&apos; T cells remained decreased up to 6 years after irradiation. The number of CD8 T lymphocytes did not change during or after treatment. Because of the decrease of a subset of CD4 cells, and the unchanged values of CD8 cells, the CD4/CD8 ratio decreased significantly after irradiation, and remained lower than before treatment up to 5-6 years after radiotherapy. The number of both HLA-DR positive CD4 and HLA-DR positive CD8 T cells (&apos;'activated'&apos; T cells) increased significantly after irradiation. The natural killer (NK) cells were not affected by treatment. The authors propose that recovery of the CD4 cells is limited to the CD4-w29 (&apos;'memory'&apos;) population because of thymic dysfunction in older humans. (Author).

  8. Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I

    DEFF Research Database (Denmark)

    Rajakumar, Chandheeb; Ban, Matthew R; Cao, Henian


    the population frequency of this variant, we determined CPT1A p.P479L genotypes in 1111 Greenland Inuit. Associations between genotype and variation in plasma total cholesterol, triglycerides, LDL, HDL, apolipoprotein (apo) B, and apo A-I were also investigated. We found the L479 allele occurs at a high...... subsequently studied. However, CPT1A p.P479L was associated with elevated plasma HDL and apo A-I levels. The association with increased levels of HDL and apo A-I suggest that the polymorphism might protect against atherosclerosis....

  9. Localized irradiations, Evaluation through &apos;&apos;comet assay&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Giorgio, M.D.; Taja, M.R.; Nasazzi, N.B. [Autoridad Regulatoria Nuclear (Argentina); Bustos, N.; Cavalieri, H.; Bolgiani, A.


    During the last 50 years various radiation accidents involving localized irradiations occurred, resulting mainly from improper handling of sealed sources Co{sup 60}, Cs{sup 137} or Ir{sup 192} at workplaces for industrial gammagraphy. Severe skin reaction may develop at the contact sites. Such inhomogeneous irradiations lead to a differential exposure of lymphocytes in lymphatic tissues or other organs that may recirculate into the peripheral blood producing a mixed irradiated and unirradiated population of lymphocytes. Applying the mathematical models &apos;&apos;Contaminated Poisson&apos;&apos; of Dolphin and Qdr method of Sasaki, a mean dose in the irradiated body area and its size can be estimated from unstable chromosome aberration scoring. This give an indication of the proportion of haemopoietic stem cell compartment involved in the overexposure. There are also different biophysical techniques that can give responses in biological dosimetry. The &apos;&apos;Comet Assay&apos;&apos; (single cell gel electrophoresis) is a sensitive and rapid method for DNA strand break detection in individual cells. The advantages of the technique include: collection of data at the level of individual cell; the need for small numbers of cells per sample; its sensitivity for detecting DNA damage and that virtually any eukaryote cell population is amenable to analysis. The objective of this work is to apply &apos;&apos;Comet Assay&apos;&apos; method to evaluate the effect of radiation on skin and subcutaneous tissues, differentiating irradiated from unirradiated body areas. It could provide a useful tool to estimate the extension and the dose in the irradiated region, contributing with the current techniques. In this first study, we evaluate the alkaline comet assay as a method for detection of DNA radiation induced damage in keratinocytes from primary culture obtained from full thickness skin biopsies of patients requiring grafts. Skin and, particularly, keratinocytes were

  10. Both serum apolipoprotein B and the apolipoprotein B/apolipoprotein A-I ratio are associated with carotid intima-media thickness.

    Directory of Open Access Journals (Sweden)

    Fei Huang

    Full Text Available BACKGROUND: Previous studies indicated that apolipoprotein measurements predicted cardiovascular disease (CVD risk; however, associations between apolipoproteins and carotid intima-media thickness (CIMT were less explored. METHODOLOGY AND PRINCIPAL FINDINGS: The cross-sectional study included 6069 participants aged 40 years or older with NGT from Shanghai, China. Serum fasting traditional lipids (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG], apoA-I and apoB were assessed. A high-resolution B-mode ultrasonography was performed to measure CIMT. We found CIMT increased progressively across the quartiles of serum apoB (p for trend <0.0001. In logistic regression, concentrations of apoB (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.18-1.36, TC (OR 1.23, 95% CI 1.14-1.32, LDL-C (OR 1.25, 95% CI 1.16-1.34 and TG (OR 1.11, 95% CI 1.04-1.20 were significantly related to elevated CIMT after adjusted for age and sex. Meanwhile, the apoB/apoA-I ratio (OR 1.25, 95% CI 1.17-1.34 related to elevated CIMT. ApoB (OR 1.23, 95% CI 1.00-1.51 and the apoB/apoA-I ratio (OR 1.19, 95% CI 1.04-1.36 remained significantly associated with elevated CIMT, after adjusted for the traditional CVD risk factors including traditional lipids. CONCLUSIONS AND SIGNIFICANCE: There were significant associations between serum apoB, the apoB/apoA-I ratio and elevated CIMT. Serum apoB and the apoB/apoA-I ratio might be independent predictors of early atherosclerosis in NGT.

  11. A &apos;'Toolbox'&apos;21 Equivalent Process for Safety Analysis Software

    Energy Technology Data Exchange (ETDEWEB)

    O' KULA, KR


    Defense Nuclear Facilities Safety Board (DNFSB) Recommendation 2002-1 (Quality Assurance for Safety-Related Software) identified a number of quality assurance issues on the use of software in Department of Energy (DOE) facilities for analyzing hazards, and designing and operating controls that prevent or mitigate potential accidents. The development and maintenance of a collection, or &apos;'toolbox,'&apos; of multiple-site use, standard solution, Software Quality Assurance (SQA)-compliant safety software is one of the major improvements identified in the associated DOE Implementation Plan (IP). The DOE safety analysis toolbox will contain a set of appropriately quality-assured, configuration-controlled, safety analysis codes, recognized for DOE-broad, safety basis applications. Currently, six widely applied safety analysis computer codes have been designated for toolbox consideration. While the toolbox concept considerably reduces SQA burdens among DOE users of these codes, many users of unique, single-purpose, or single-site software may still have sufficient technical justification to continue use of their computer code of choice, but are thwarted by the multiple-site condition on toolbox candidate software. The process discussed here provides a roadmap for an equivalency argument, i.e., establishing satisfactory SQA credentials for single-site software that can be deemed &apos;'toolbox-equivalent'&apos;. The process is based on the model established to meet IP Commitment Establish SQA criteria for the safety analysis &apos;'toolbox'&apos; codes. Implementing criteria that establish the set of prescriptive SQA requirements are based on implementation plan/procedures from the Savannah River Site, also incorporating aspects of those from the Waste Isolation Pilot Plant (SNL component) and the Yucca Mountain Project. The major requirements are met with evidence of a software quality assurance plan, software requirements and

  12. The Effect of Aerobic Exercise on Total Cholesterol, High-Density Lipoprotein, Apolipoprotein B, Apolipoprotein A-I, and Percent Body Fat in Adolescent Females. (United States)

    Lungo, Diane; And Others

    The effect of aerobic exercise on total cholesterol (TC), high-density lipoprotein (HDL), apolipoprotein B (Apo B), apolioprotein A-I (Apo A-I), and percent body fat in adolescent females was studied. The control subjects (n=86) were volunteers who had completed a physical education class at least six months prior to the commencement of the study,…

  13. Radmap: &apos;'as-built'&apos; cad models incorporating geometrical, radiological and material information

    Energy Technology Data Exchange (ETDEWEB)

    Piotrowski, L. [Electricite de France (EDF/DRD), 78 - Chatou (France); Lubawy, J.L. [Electricite de France (EDF/CNEPE), 37 - Tours (France)


    EDF intends to achieve successful and cost-effective dismantling of its obsolete nuclear plants. To reach this goal, EDF is currently extending its &apos;'as-built'&apos; 3-D modelling system to also include the location and characteristics of gamma sources in the geometrical models of its nuclear installations. The resulting system (called RADMAP) is a complete CAD chain covering 3-D and gamma data acquisitions, CAD modelling and exploitation of the final model. Its aim is to describe completely the geometrical and radiological state of a particular nuclear environment. This paper presents an overall view of RADMAP. The technical and functional characteristics of each element of the chain are indicated and illustrated using real (EDF) environments/applications. (author)

  14. &apos;'Beaded'&apos; osteoid osteoma: a possible transition between solitary and multicentric tumor

    Energy Technology Data Exchange (ETDEWEB)

    Chiou, Yi-You [Department of Radiology, Taipei Veterans General Hospital, 201 Sec. 2 Shih-Pai Road, 11217, Taipei (Taiwan); Rosenthal, Daniel I. [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114 (United States); Rosenberg, Andrew E. [Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114 (United States)


    An extremely rare example of an elongated (3 cm) osteoid osteoma is presented. The tumor demonstrated three focal enlargements connected by narrow areas, suggesting a &apos;&apos;string of beads&apos;&apos; in appearance. The elongated shape suggested the possibility that lesional tissue was stretched in a longitudinal fashion as a result of the rapid skeletal growth. The tumor closest to the growth plate was densely ossified, while the furthest lesion was almost completely lytic, suggesting that the tumor enlarged in a centripetal direction. This case is believed to illustrate a continuum from solitary to multicentric osteoid osteoma. The tumor was treated successfully with three separate percutaneous radiofrequency ablations during a single session. (orig.)

  15. Overview of &apos;&apos;Red Oil&apos;&apos; Frequency Analyses for F-Canyon

    Energy Technology Data Exchange (ETDEWEB)

    Lux, C.R.


    A very small potential exists in the Savannah River Site (SRS) separations operations for an uncontrolled reaction between tri-n-butyl phosphate (TBP) and nitric acid that could result in unacceptable damage to separations facilities and a significant release of radioactive materials. The recent &apos;&apos;red oil&apos;&apos; (TBP and nitric acid) accident in Tomsk, Russia, resulted in considerable damage and radioactive release. Explosions have also occurred at SRS during the early years of operations. While the SRS separations facilities have operated without incident for many years, it is prudent to revisit the SRS defense-in-depth approach to preventing such an accident and to upgrade preventive procedures and hardware as appropriate.

  16. APOE Genotyping, Cardiovascular Disease (United States)

    ... Home Visit Global Sites Search Help? APOE Genotyping, Cardiovascular Disease Share this page: Was this page helpful? Also ... of choice to decrease the risk of developing cardiovascular disease (CVD) . However, there is a wide variability in ...


    Energy Technology Data Exchange (ETDEWEB)

    Gómez, José F.; Miranda, Luis F.; Guerrero, Martín A. [Instituto de Astrofísica de Andalucía, CSIC, Glorieta de la Astronomía s/n, E-18008 Granada (Spain); Suárez, Olga; Bendjoya, Philippe; Lagadec, Eric [Laboratoire Lagrange, UMR 7293, Université de Nice Sophia-Antipolis, CNRS, Observatoire de la Côte d' Azur, F-06304 Nice (France); Rizzo, J. Ricardo; García-García, Enrique [Centro de Astrobiología (INTA-CSIC), Ctra. M-108, km. 4, E-28850 Torrejón de Ardoz (Spain); Green, James A. [CSIRO Astronomy and Space Science, Australia Telescope National Facility, P.O. Box 76, Epping, NSW 1710 (Australia); Uscanga, Lucero [Institute of Astronomy, Astrophysics, Space Applications and Remote Sensing, National Observatory of Athens, 15236 Athens (Greece); Ramos-Larios, Gerardo [Instituto de Astronomía y Meteorología, Av. Vallarta No. 2602, Col. Arcos Vallarta, C.P. 44130 Guadalajara, Jalisco (Mexico)


    &apos;&apos;Water fountains&apos;&apos; (WFs) are evolved objects showing high-velocity, collimated jets traced by water maser emission. Most of them are in the post-asymptotic giant branch (post-AGB) and they may represent one of the first manifestations of collimated mass loss in evolved stars. We present water maser, carbon monoxide, and mid-infrared spectroscopic data (obtained with the Australia Telescope Compact Array, Herschel Space Observatory, and the Very Large Telescope, respectively) toward IRAS 15103–5754, a possible planetary nebula (PN) with WF characteristics. Carbon monoxide observations show that IRAS 15103–5754 is an evolved object, while the mid-IR spectrum displays unambiguous [Ne II] emission, indicating that photoionization has started and thus, its nature as a PN is confirmed. Water maser spectra show several components spreading over a large velocity range (≅ 75 km s{sup –1}) and tracing a collimated jet. This indicates that the object is a WF, the first WF known that has already entered the PN phase. However, the spatial and kinematical distribution of the maser emission in this object are significantly different from those in other WFs. Moreover, the velocity distribution of the maser emission shows a &apos;'Hubble-like'&apos; flow (higher velocities at larger distances from the central star), consistent with a short-lived, explosive mass-loss event. This velocity pattern is not seen in other WFs (which are presumably in earlier evolutionary stages). We therefore suggest that we are witnessing a fundamental change of mass-loss processes in WFs, with water masers being pumped by steady jets in post-AGB stars, but tracing explosive/ballistic events as the object enters the PN phase.

  18. Major disruption of D&apos;&apos; beneath Alaska: D&apos;&apos; Beneath Alaska

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Daoyuan [Laboratory of Seismology and Physics of Earth' s Interior, School of Earth and Space Sciences, University of Science and Technology of China, Hefei Anhui China; National Geophysics Observatory at Mengcheng, Anhui China; Helmberger, Don [Seismological Laboratory, California Institute of Technology, Caltech, Pasadena California USA; Miller, Meghan S. [Department of Earth Sciences, University of Southern California, Los Angeles California USA; Jackson, Jennifer M. [Seismological Laboratory, California Institute of Technology, Caltech, Pasadena California USA


    D&apos;&apos; represents one of the most dramatic thermal and compositional layers within our planet. In particular, global tomographic models display relatively fast patches at the base of the mantle along the circum-Pacific which are generally attributed to slab debris. Such distinct patches interact with the bridgmanite (Br) to post-bridgmanite (PBr) phase boundary to generate particularly strong heterogeneity at their edges. Most seismic observations for the D&apos;&apos; come from the lower mantle S wave triplication (Scd). Here we exploit the USArray waveform data to examine one of these sharp transitions in structure beneath Alaska. From west to east beneath Alaska, we observed three different characteristics in D&apos;&apos;: (1) the western region with a strong Scd, requiring a sharp δVs = 2.5% increase; (2) the middle region with no clear Scd phases, indicating a lack of D&apos;&apos; (or thin Br-PBr layer); and (3) the eastern region with strong Scd phase, requiring a gradient increase in δVs. To explain such strong lateral variation in the velocity structure, chemical variations must be involved. We suggest that the western region represents relatively normal mantle. In contrast, the eastern region is influenced by a relic slab that has subducted down to the lowermost mantle. In the middle region, we infer an upwelling structure that disrupts the Br-PBr phase boundary. Such an interpretation is based upon a distinct pattern of travel time delays, waveform distortions, and amplitude patterns that reveal a circular-shaped anomaly about 5° across which can be modeled synthetically as a plume-like structure rising about 400 km high with a shear velocity reduction of ~5%, similar to geodynamic modeling predictions of upwellings.

  19. The plasma concentration of HDL-associated apoM is influenced by LDL receptor-mediated clearance of apoB-containing particles. (United States)

    Christoffersen, Christina; Benn, Marianne; Christensen, Pernille M; Gordts, Philip L S M; Roebroek, Anton J M; Frikke-Schmidt, Ruth; Tybjaerg-Hansen, Anne; Dahlbäck, Björn; Nielsen, Lars B


    ApoM is mainly associated with HDL. Nevertheless, we have consistently observed positive correlations of apoM with plasma LDL cholesterol in humans. Moreover, LDL receptor deficiency is associated with increased plasma apoM in mice. Here, we tested the idea that plasma apoM concentrations are affected by the rate of LDL receptor-mediated clearance of apoB-containing particles. We measured apoM in humans each carrying one of three different LDL receptor mutations (n = 9) or the apoB3500 mutation (n = 12). These carriers had increased plasma apoM (1.34 ± 0.13 µM, P = 0.003, and 1.23 ± 0.10 µM, P = 0.02, respectively) as compared with noncarriers (0.93 ± 0.04 µM). When we injected human apoM-containing HDL into Wt (n = 6) or LDL receptor-deficient mice (n = 6), the removal of HDL-associated human apoM was delayed in the LDL receptor-deficient mice. After 2 h, 54 ± 5% versus 90 ± 8% (P LDL receptor-deficient mice, respectively. Finally, we compared the turnover of radio-iodinated LDL and plasma apoM concentrations in 45 normocholesterolemic humans. There was a negative correlation between plasma apoM and the fractional catabolic rate of LDL (r = -0.38, P = 0.009). These data suggest that the plasma clearance of apoM, despite apoM primarily being associated with HDL, is influenced by LDL receptor-mediated clearance of apoB-containing particles.

  20. Comments on &apos;The discrepancy between human peripheral nerve chronaxie times as measured using magnetic and electric field stimuli: the relevance to MRI gradient coil safety&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Patrick Reilly, J [Applied Physics Laboratory, Johns Hopkins University, Laurel, MD (United States)], E-mail:


    A recent electrostimulation study with human subjects (Recoskie et al 2009 Phys. Med. Biol. 54 5965-79) reported a large difference between chronaxie times when stimuli were delivered to the same body locus (the wrist) either through contact electrodes (electric stimulation) or through a pulsed magnetic field (magnetic stimulation). This paper reviews the procedures and analytic methods used in that study that might account for the reported discrepancies. Factors possibly accounting for reported discrepancies include the maximum and minimum pulse widths of the experimental stimuli; variations in experimental waveforms vis-a-vis mathematically ideal functions; differences in the spatial distribution of the in situ electric field for the two methods of delivery and differences in derived chronaxie relative to strength-duration time constants. (letter to the editor)

  1. Trends in Energy. &apos;The consumer decides&apos;; Trends in Energy. &apos;De consument bepaalt&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Brzezowsky-Ruys, Y.; Van der Zalm, M.; Van Zutphen, M. (eds.)


    A report is given of the Capgemini organised congress &apos;Trends in Energy 2011&apos; which has the Dutch subtitle &apos;De consument bepaalt&apos; (The consumer decides&apos;. The focus of the articles, interviews, debates and presentations is on the role of the consumer in the supply of and demand for energy. Parts of the report are in Dutch and English [Dutch] Dit rapport bestaat uit een verslag van het congres &apos;Trends in Energy 2011. De consument bepaalt&apos; en een aantal artikelen met achtergrondinformatie over onder meer de rol van de consument in vraag en aanbod van energie.

  2. Backbone and sidechain 1H, 13C and 15N resonance assignments of the human brain-type fatty acid binding protein (FABP7) in its apo form and the holo forms binding to DHA, oleic acid, linoleic acid and elaidic acid

    DEFF Research Database (Denmark)

    Oeemig, Jesper S; Jørgensen, Mathilde L; Hansen, Mikka S


    In this manuscript, we present the backbone and side chain assignments of human brain-type fatty acid binding protein, also known as FABP7, in its apo form and in four different holo forms, bound to DHA, oleic acid, linoleic acid and elaidic acid.......In this manuscript, we present the backbone and side chain assignments of human brain-type fatty acid binding protein, also known as FABP7, in its apo form and in four different holo forms, bound to DHA, oleic acid, linoleic acid and elaidic acid....

  3. Glyoxalase 1 overexpression does not affect atherosclerotic lesion size and severity in ApoE-/- mice with or without diabetes

    DEFF Research Database (Denmark)

    Hanssen, Nordin M J; Brouwers, Olaf; Gijbels, Marion J


    AIMS: Advanced glycation end-products (AGEs) and their precursors have been associated with the development of atherosclerosis. We recently discovered that glyoxalase 1 (GLO1), the major detoxifying enzyme for AGE precursors, is decreased in ruptured human plaques, and that levels of AGEs......E(-/-) huGLO1(+/-) (n = 20) mice. To induce diabetes, we injected a subset with streptozotocin (STZ) to generate diabetic ApoE(-/-) (n = 8) and ApoE(-/-) huGLO1(+/-) (n = 13) mice. All mice were fed chow and sacrificed at 25 weeks of age. The GLO1 activity was three-fold increased in huGLO1(+/-) aorta......(+/-) overexpression. Although diabetic mice showed decreased GLO1 expression (P diabetic mice, GLO1 overexpression also did not affect the aortic root lesion size or inflammation in diabetic mice. CONCLUSION: In ApoE(-/-) mice with or without...

  4. Apolipoprotein A-I configuration and cell cholesterol efflux activity of discoidal lipoproteins depend on the reconstitution process. (United States)

    Cuellar, Luz Ángela; Prieto, Eduardo Daniel; Cabaleiro, Laura Virginia; Garda, Horacio Alberto


    Discoidal high-density lipoproteins (D-HDL) are critical intermediates in reverse cholesterol transport. Most of the present knowledge of D-HDL is based on studies with reconstituted lipoprotein complexes of apolipoprotein A-I (apoA-I) obtained by cholate dialysis (CD). D-HDL can also be generated by the direct microsolubilization (DM) of phospholipid vesicles at the gel/fluid phase transition temperature, a process mechanistically similar to the "in vivo" apoAI lipidation via ABCA1. We compared the apoA-I configuration in D-HDL reconstituted with dimyristoylphosphatidylcholine by both procedures using fluorescence resonance energy transfer measurements with apoA-I tryptophan mutants and fluorescently labeled cysteine mutants. Results indicate that apoA-I configuration in D-HDL depends on the reconstitution process and are consistent with a "double belt" molecular arrangement with different helix registry. As reported by others, a configuration with juxtaposition of helices 5 of each apoAI monomer (5/5 registry) predominates in D-HDL obtained by CD. However, a configuration with helix 5 of one monomer juxtaposed with helix 2 of the other (5/2 registry) would predominate in D-HDL generated by DM. Moreover, we also show that the kinetics of cholesterol efflux from macrophage cultures depends on the reconstitution process, suggesting that apoAI configuration is important for this HDL function.

  5. Solid state laser technology for inertial confinement fusion: A collection of articles from &apos;&apos;Energy and Technology Review&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)


    This paper contains reprinted articles that record several milestones in laser research at LLNL. &apos;&apos;Neodymium-Glass Laser Research and Development at LLNL&apos;&apos; recounts the history of the Laser Program and our work on neodymium-glass lasers. &apos;&apos;Nova Laser Technology&apos;&apos; describes the capabilities of the Nova laser and some of its uses. &apos;&apos;Building Nova: Industry Relations and Technology Transfer&apos;&apos; illustrates the Laboratory&apos;s commitment to work with US industry in technology development. &apos;&apos;Managing the Nova Laser Project&apos;&apos; details the organization and close monitoring of costs and schedules during the construction of the Nova laser facility. The article &apos;&apos;Optical Coatings by the Sol-Gel Process,&apos;&apos; describes our chemical process for making the damage-resistant, antireflective silica coatings used on the Nova laser glass. The technical challenges in designing and fabricating the KDP crystal arrays used to convert the light wave frequency of the Nova lasers are reported in &apos;&apos;Frequency Conversion of the Nova Laser.&apos;&apos; Two articles, &apos;&apos;Eliminating Platinum Inclusions in Laser Glass&apos;&apos; and &apos;&apos;Detecting Microscopic Inclusions in Optical Glass,&apos;&apos; describe how we dealt with the problem of damaging metal inclusions in the Nova laser glass. The last article reprinted here, &apos;&apos;Auxilliary Target Chamber for Nova,&apos;&apos; discusses the diversion of two of Nova&apos;s ten beamlines into a secondary chamber for the purpose of increasing our capacity for experimentation.

  6. Fiscal 1999 research report on long-term energy technology strategy. Basic research on industrial technology strategy (Individual technology strategy). Electronic information technology field (Human process ware field for computers); 1999 nendo choki energy gijutsu senryaku nado ni kansuru chsao hokokusho. Sangyo gijutsu senryaku sakutei kiban chosa (bun&apos;yabetsu gijutsu senryaku) denshi joho gijutsu bun&apos;ya (computer kanren bun&apos;ya no uchi, human process wear bun&apos;ya)

    Energy Technology Data Exchange (ETDEWEB)



    This report summarizes the fiscal 1999 basic research result on industrial technology strategy of a human process ware (HPW) field on electronic information. Although the current HPW industry is not yet complete, various technologies concerned are being stored, and the HPW industry is expected as new major industry for home and personal information equipment. As factors hindering technological innovation in Japan, the incomplete market, poor cooperation between industry and government, ambiguous role of university, and poor standardization were pointed out. Technology trends were analyzed to extract seed technology fields from 3 viewpoints of mobile HPW available at any time, at any place and to anybody, HPW system capable of customizing every personal use, and HPW supporting development of a creativity. As general strategy, the technology seed chart and map of technical development targets for every HPW were prepared to conceive a route to practical use, and develop element technologies required for practical use, based on the future trend of the market. (NEDO)

  7. In vitro cytotoxic effects of PM{sub 2.5} from the city of Abidjan (Ivory Coast) on human A549 lung cells; Effets cytotoxiques in vitro des PM{sub 2,} {sub 5} de la ville d&apos;Abidjan (Cote-d&apos;Ivoire) sur des cellules pulmonaires humaines

    Energy Technology Data Exchange (ETDEWEB)

    Kouassi, Kouakou-Serge [Universite Lille Nord de France, Lille (France); Unite de Chimie Environnementale et Interactions sur le Vivant, EA 4492 MREI, Universite du Littoral Cote d' Opale, Dunkerque (France); Universite Cocody-Abidjan et Institut Pasteur, Abidjan (Cote d' Ivoire); Billet, Sylvain; Garcon, Guillaume; Verdin, Anthony; Courcot, Dominique; Shirali, Pirouz [Universite Lille Nord de France, Lille (France); Unite de Chimie Environnementale et Interactions sur le Vivant, EA 4492 MREI, Universite du Littoral Cote d' Opale, Dunkerque (France); Diouf, Amadou [Laboratoire de Toxicologie, Faculte de Medecine Pharmacologie Odontologie, Universite Cheikh Anta Diop, Dakar (Senegal); Cazier, Fabrice [Universite Lille Nord de France, Lille (France); Centre Commun de Mesures, MREI 1, Universite du Littoral Cote d' Opale, Dunkerque (France); Djaman, Joseph [Universite Cocody-Abidjan et Institut Pasteur, Abidjan (Cote d' Ivoire)


    Epidemiological studies associate air pollution, especially particulate, increased morbidity and mortality from respiratory and cardiovascular origin . Africa, which has an urbanization rate among the highest in the world, is particularly exposed. The &apos;Initiative on the air quality in Sub-Saharan Africa&apos; showed the importance of atmospheric concentrations of certain pollutants such as nitrogen oxides, sulfur dioxide and particulate matter (PM{sub 10}). Like the great capitals of Africa, Abidjan, economic capital and most industrialized city of Ivory Coast is facing an air pollution from industrial-urban and health consequences for its population of nearly 6 million inhabitants. To better understand the mechanisms of action resulting from pulmonary exposure to particulate atmospheric aerosols, we proposed: (i) to collect atmospheric particles (PM{sub 2.5}) using high volume cascade impaction in the District of Abidjan in three influences (rural, urban or industrial), (ii) to determine their main physicochemical, (iii) assess their cytotoxicity and their role in the induction of oxidative damage in a model of human lung cells (A549) in culture. The chemical composition of the atmospheric particles revealed their heterogeneity, and many inorganic (e.g. Al, Ca, Fe, Mn, Zn, Ni, Cr, Cu, Pb, Mg) and organic compounds (e.g. paraffins) were quantified at the three sites. Their effect concentrations (EC) to 10 and 50% on the A549 were as follows: influence rural: EC{sub 10} = 5.91 {mu}g/cm{sup 2} and EC{sub 50} 29.55 {mu}g/cm{sup 2}, urban influence: EC{sub 10} = 5 .45 {mu}g/cm{sup 2} and EC{sub 50} = 27.23 {mu}g/cm{sup 2}, and industrial influence: EC{sub 10} = 6.86 {mu}g/cm{sup 2} and EC{sub 50} = 34.29 {mu}g/cm{sup 2}. Exposure of A549 cells to Abidjan city&apos;s PM samples for 24, 48 or 72 hours to their EC{sub 10} or EC{sub 50} induced oxidative damage, as demonstrated by the formation of malon-dialdehyde, changes in enzyme activity of superoxide dismutase

  8. Switzerland as Europe&apos;s &apos;'battery'&apos;. Wishful dream or reality?; Die Schweiz als &apos;&apos;Batterie Europas&apos;&apos;. Utopie oder Realitaet?

    Energy Technology Data Exchange (ETDEWEB)

    Kammer, Adrian; Zurmuehle, Damian; Salzmann, Michael; Baumgartner, Raphael; Mignone, Domenico [Bernische Kraftwerke (BKW), Bern (Switzerland). Energiewirtschaftliche Planung und Prognose


    There are plans for Swiss pumped hydrostorage systems to absorb large quantities of excess electricity from European wind and solar power generation. Model-based analyses have shown however that &apos;'Europe&apos;s battery&apos;&apos;, as Switzerland would like to see itself, will not be needed until the middle of this century. Even if all extension projects currently in progress should be completed, Switzerland will not have sufficient pump capacity or import capacity to absorb large amounts of excess electricity. Furthermore, the primary means of making storage capacity available for import electricity would be to reduce reservoir power plant capacity. In view of all this Switzerland&apos;s hopes for a role as a major European electricity storage provider appear somewhat exaggerated even in the long-term perspective.

  9. Single-molecule folding mechanisms of the apo- and Mg2+-bound states of human neuronal calcium sensor-1

    DEFF Research Database (Denmark)

    Naqvi, Mohsin M; Heiðarsson, Pétur Orri; Otazo, Mariela R;


    in a variety of cellular processes in which it has been linked to a number of disorders such as schizophrenia and autism. Despite extensive studies on the Ca(2+)-activated state of NCS proteins, little is known about the conformational dynamics of the Mg(2+)-bound and apo states, both of which are populated...... by populating one intermediate state consisting of a folded C-domain and an unfolded N-domain. The interconversion at equilibrium between the different molecular states populated by NCS-1 was monitored in real time through constant-force measurements and the energy landscapes underlying the observed transitions......Neuronal calcium sensor-1 (NCS-1) is the primordial member of a family of proteins responsible primarily for sensing changes in neuronal Ca(2+) concentration. NCS-1 is a multispecific protein interacting with a number of binding partners in both calcium-dependent and independent manners, and acting...

  10. Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice

    NARCIS (Netherlands)

    Leppänen, P.; Luoma, J.S.; Hofker, M.H.; Havekes, L.M.; Ylä-Herttuala, S.


    Apo E3-leiden transgenic mice express human dysfunctional apo E variant and develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet. We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic mice using immunocytochemical methods in order to examine foam

  11. Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice

    NARCIS (Netherlands)

    Leppänen, P.; Luoma, J.S.; Hofker, M.H.; Havekes, L.M.; Ylä-Herttuala, S.


    Apo E3-leiden transgenic mice express human dysfunctional apo E variant and develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet. We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic mice using immunocytochemical methods in order to examine foam

  12. Chromosomes and irradiation: in vitro study of the action of X-rays on human lymphocytes; Chromosomes et radiations: etude in vitro de l&apos;action des rayons X sur les lymphocytes humains

    Energy Technology Data Exchange (ETDEWEB)

    Mouriquand, C.; Patet, J.; Gilly, C.; Wolff, C


    Radioinduced chromosomal aberrations were studied in vitro on leukocytes of human peripheral blood after x irradiation at 25, 50, 100, 200, and 300 R. The numeric and structural anomalies were examined on 600 karyotypes. The relationship between these disorders and the dose delivered to the blood are discussed. An explanation on their mechanism of formation is tentatively given. (authors) [French] L&apos;etude in vitro des anomalies chromosomiques radioinduites a ete pratiquee sur des leucocytes de sang peripherique preleve chez 4 sujets et irradie aux doses de 25, 50, 100, 200, 300 R. Les aberrations numeriques et structurales ont ete examinees sur 600 caryotypes. Les rapports entre ces anomalies et les doses appliquees sont etudies. Une hypothese sur leur mecanisme de formation est avancee. (auteurs)

  13. &apos;&apos;Black Bone&apos;&apos; MRI: a potential alternative to CT with three-dimensional reconstruction of the craniofacial skeleton in the diagnosis of craniosynostosis

    Energy Technology Data Exchange (ETDEWEB)

    Eley, Karen A. [University of Oxford, John Radcliffe Hospital, Nuffield Department of Surgical Sciences, Oxford (United Kingdom); University of Cambridge, Addenbrookes Hospital, Department of Radiology, Cambridge (United Kingdom); Watt-Smith, Stephen R. [University of Oxford, John Radcliffe Hospital, Nuffield Department of Surgical Sciences, Oxford (United Kingdom); University College London, Eastman Dental Institute, London (United Kingdom); Sheerin, Fintan [University of Oxford, John Radcliffe Hospital, Nuffield Department of Surgical Sciences, Oxford (United Kingdom); Oxford University Hospitals NHS Trust, Oxford (United Kingdom); Golding, Stephen J. [University of Oxford, John Radcliffe Hospital, Nuffield Department of Surgical Sciences, Oxford (United Kingdom)


    To determine the potential of novel gradient echo parameters, &apos;&apos;Black Bone&apos;&apos; MRI as an alternative to CT in the identification of normal and prematurely fused cranial sutures both in 2D and 3D imaging. Thirteen children with a clinical diagnosis of craniosynostosis underwent &apos;&apos;Black Bone&apos;&apos; MRI in addition to routine cranial CT. &apos;&apos;Black Bone&apos;&apos; datasets were compared to CT and clinical findings. &apos;&apos;Black Bone&apos;&apos; imaging was subsequently used to develop 3D reformats of the craniofacial skeleton to enhance further visualisation of the cranial sutures. Patent cranial sutures were consistently identified on &apos;&apos;Black Bone&apos;&apos; MRI as areas of increased signal intensity. In children with craniosynostosis the affected suture was absent, whilst the remaining patent sutures could be visualised, consistent with CT and clinical findings. Segmentation of the &apos;&apos;Black Bone&apos;&apos; MRI datasets was successful with both threshold and volume rendering techniques. The cranial sutures, where patent, could be visualised throughout their path. Patent cranial sutures appear as areas of increased signal intensity on &apos;&apos;Black Bone&apos;&apos; MRI distinct from the cranial bone, demonstrating considerable clinical potential as a non-ionising alternative to CT in the diagnosis of craniosynostosis. (orig.)

  14. New quality assurance program integrating &apos;&apos;modern radiotherapy&apos;&apos; within the German Hodgkin Study Group

    Energy Technology Data Exchange (ETDEWEB)

    Kriz, J.; Haverkamp, U.; Eich, H.T. [University of Muenster, Department of Radiation Oncology, Muenster (Germany); Baues, C.; Marnitz-Schulze, S. [University of Cologne, Department of Radiation Oncology, Koeln (Germany); Engenhart-Cabillic, R. [University of Marburg, Department of Radiation Oncology, Marburg (Germany); Herfarth, K. [University of Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Lukas, P. [University of Innsbruck, Department of Radiation Oncology, Innsbruck (Austria); Schmidberger, H. [University of Mainz, Department of Radiation Oncology, Mainz (Germany); Fuchs, M.; Engert, A. [University of Cologne, Department of Internal Medicine, Koeln (Germany)


    Field design changed substantially from extended-field RT (EF-RT) to involved-field RT (IF-RT) and now to involved-node RT (IN-RT) and involved-site RT (IS-RT) as well as treatment techniques in radiotherapy (RT) of Hodgkin&apos;s lymphoma (HL). The purpose of this article is to demonstrate the establishment of a quality assurance program (QAP) including modern RT techniques and field designs within the German Hodgkin Study Group (GHSG). In the era of modern conformal RT, this QAP had to be fundamentally adapted and a new evaluation process has been intensively discussed by the radiotherapeutic expert panel of the GHSG. The expert panel developed guidelines and criteria to analyse &apos;'modern'&apos; field designs and treatment techniques. This work is based on a dataset of 11 patients treated within the sixth study generation (HD16-17). To develop a QAP of &apos;&apos;modern RT&apos;&apos;, the expert panel defined criteria for analysing current RT procedures. The consensus of a modified QAP in ongoing and future trials is presented. With this schedule, the QAP of the GHSG could serve as a model for other study groups. (orig.) [German] Nicht nur die Zielvolumendefinitionen haben sich von der Extended-Field- (EF-RT) ueber die Involved-Field- (IF-RT) bis zur Involved-Node- (IN-RT) und Involved-Site-Radiotherapie (IS-RT) weiterentwickelt. Auch die Radiotherapie(RT)-Techniken in der Behandlung von Patienten mit Hodgkin-Lymphom haben Aenderungen erfahren. Wir moechten aufzeigen, wie die Arbeit des Qualitaetssicherungsprogramms (QAP) innerhalb der Deutschen Hodgkin Studiengruppe (German Hodgkin Study Group [GHSG]) in der Aera der &apos;&apos;modernen RT&apos;&apos; hinsichtlich intensitaetsmodulierter RT (IMRT) und bildgefuehrter RT (IGRT), aber auch hinsichtlich moderner Felddefinitionen wie bei der IN-RT angepasst wurde. In der Aera der &apos;&apos;modernen RT&apos;&apos; wurde das QAP vom radiotherapeutischen Expertenpanel der GHSG im Rahmen einiger

  15. Response of &apos;Nagpur&apos; mandarin, &apos;Mosambi&apos; sweet orange and &apos;Kagzi&apos; acid lime to gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ladaniya, M.S. E-mail:; Singh, Shyam; Wadhawan, A.K


    The effects of irradiation dose and refrigerated storage conditions on &apos;Nagpur&apos; mandarin (Citrus reticulata Blanco), &apos;Mosambi&apos; sweet orange (Citrus sinensis Osbeck) and &apos;Kagzi&apos; acid lime (Citrus aurantifolia Swingle) were investigated. Mature fruits of these three species were treated with 0, 0.25, 0.5, 1 and 1.5 kGy radiation. &apos;Nagpur&apos; mandarin and &apos;Mosambi&apos; sweet oranges were stored at 6-7 deg. C and 90-95% r.h. for 75 and 90 days, respectively, while &apos;Kagzi&apos; acid limes were stored at 8{+-}1 deg. C and 90-95% r.h. for 90 days. Physico-chemical parameters, sensory attributes and respiration rate were measured besides losses and disorders. In &apos;Nagpur&apos; mandarin, radiation dose upto 1.5 kGy did not cause any rind disorder. Radiation treatments did not reduce the extent of decay. Penicillium rot was delayed in fruit treated with 1.5 kGy, while it appeared early in 0 kGy. Irradiation doses were ineffective to control rots due to Botryodiplodia theobromae and Alternaria citri. Doses upto 1.5 kGy did not cause any significant effect on fruit firmness and juice content; however, total soluble solids increased, while titratable acidity and vitamin &apos;C&apos; content decreased. Texture and flavour scores as recorded after a week, were not affected by irradiation except in 1.5 kGy. In &apos;Mosambi&apos; sweet orange, radiation treatments caused peel disorder in the form of brown sunken areas after 90 days and reduced fruit firmness, acidity and vitamin C content. The TSS content was higher in treated fruit. Flavour and texture were not affected by the doses of irradiation used. In treated acid limes (mature yellow), weight loss and decay were higher than untreated fruit (0 kGy) although difference was non-significant. Juice, TSS, titratable acidity and vitamin C contents were significantly less in treated fruit than in 0 kGy. Texture and flavour scores were also less in treated fruit than in 0 kGy. The

  16. ApoE and Quality of Life in Nonagenarians (United States)

    Parsaik, Ajay K; Lapid, Maria I.; Rummans, Teresa A.; Cha, Ruth H.; Boeve, Bradley F.; Pankratz, Vernon (Shane) S.; Tangalos, Eric G.; Petersen, Ronald C.


    Objectives ApoE ε4 is associated with adverse health conditions that negatively impact the quality of life (QOL). The relationship between ApoE ε4 and QOL has not been explored in the oldest old. Our study aimed to examine ApoE in the oldest old, and explore its association with QOL. Design Cross-sectional cohort study. Setting A medium sized community in Olmsted County, Minnesota, USA. Participants 90–99 year old individuals living independently or in long term care environments. Measurements We collected demographic information and measured cognitive function (Short Test of Mental Status [STMS], Mini-Mental State Examination [MMSE], Mattis Dementia Rating Scale [DRS]), QOL (Linear Analogue Self Assessment [LASA]) and ApoE distribution. Subjects were classified as cognitively normal, mild cognitive impairment (MCI), dementia (DEM), or dementia with stroke and/or parkinsonism (DEMSP). Regression model was used to assess the predictors of QOL. Results 121 subjects (45 cognitively normal, 13 MCI, 34 DEM, 29 DEMSP) aged 90–99,106 (87.6 %) females, were included. Frequency of ApoE ε3 allele was highest [194 (80.2%): ε2/3 18, ε3/3 77, ε3/4 22] followed by ApoE ε4 [25 (10.3%): ε2/4 3, ε3/4 22] and ApoE ε2 [23 (9.5%; ε2/2 1, ε2/3 18, ε2/4 3]. None of the subjects carried ApoE ε4/4 genotype. QOL was similar between ApoE ε4 carrier and non-carriers. Physical well-being, emotional well-being, intellectual well-being, social connectedness and coping ability were positively associated with QOL, whereas male gender, DEMSP, pain frequency and pain severity were negatively associated. Conclusions The most common ApoE in the oldest old was ε3/3 genotype and ε3 allele. No association was found between ApoE ε4 and QOL. However, those with high physical, emotional and intellectual well being, social connectedness and coping ability had the highest overall QOL. PMID:22863665

  17. The secondary structure of apolipoprotein A-I on 9.6-nm reconstituted high-density lipoprotein determined by EPR spectroscopy (United States)

    Oda, Michael N; Budamagunta, Madhu S; Borja, Mark S; Petrlova, Jitka; Voss, John C; Lagerstedt, Jens O


    Apolipoprotein A-I (ApoA-I) is the major protein component of high-density lipoprotein (HDL), and is critical for maintenance of cholesterol homeostasis. During reverse cholesterol transport, HDL transitions between an array of subclasses, differing in size and composition. This process requires ApoA-I to adapt to changes in the shape of the HDL particle, transiting from an apolipoprotein to a myriad of HDL subclass-specific conformations. Changes in ApoA-I structure cause alterations in HDL-specific enzyme and receptor-binding properties, and thereby direct the HDL particle through the reverse cholesterol transport pathway. In this study, we used site-directed spin label spectroscopy to examine the conformational details of the ApoA-I central domain on HDL. The motional dynamics and accessibility to hydrophobic/hydrophilic relaxation agents of ApoA-I residues 99–163 on 9.6-nm reconstituted HDL was analyzed by EPR. In previous analyses, we examined residues 6–98 and 164–238 (of ApoA-I's 243 residues), and combining these findings with the current results, we have generated a full-length map of the backbone structure of reconstituted HDL-associated ApoA-I. Remarkably, given that the majority of ApoA-I's length is composed of amphipathic helices, we have identified nonhelical residues, specifically the presence of a β-strand (residues 149–157). The significance of these nonhelical residues is discussed, along with the other features, in the context of ApoA-I function in contrast to recent models derived by other methods. PMID:23668303

  18. Stimulation of Hepatic Apolipoprotein A-I Production by Novel Thieno-Triazolodiazepines: Roles of the Classical Benzodiazepine Receptor, PAF Receptor, and Bromodomain Binding. (United States)

    Kempen, Herman J; Bellus, Daniel; Fedorov, Oleg; Nicklisch, Silke; Filippakopoulos, Panagis; Picaud, Sarah; Knapp, Stefan


    Expression and secretion of apolipoprotein A-I (apoA-I) by cultured liver cells can be markedly stimulated by triazolodiazepines (TZDs). It has been shown previously that the thieno-TZD Ro 11-1464 increases plasma levels of apoA-I and in vivomacrophage reverse cholesterol transport in mice. However, these effects were only seen at high doses, at which the compound could act on central benzodiazepine (BZD) receptors or platelet activating factor (PAF) receptors, interfering with its potential utility. In this work, we describe 2 new thieno-TZDs MDCO-3770 and MDCO-3783, both derived from Ro 11-1464. These compounds display the same high efficacy on apoA-I production, metabolic stability, and lack of cytotoxicity in cultured hepatocytes as Ro 11-1464, but they do not bind to the central BZD receptor and PAF receptor. The quinazoline RVX-208 was less efficacious in stimulating apoA-I production and displayed signs of cytotoxicity. Certain TZDs stimulating apoA-I production are now known to be inhibitors of bromodomain (BRD) extra-terminal (BET) proteins BRDT, BRD2, BRD3, and BRD4, and this inhibition was inferred as a main molecular mechanism for their effect on apoA-I expression. We show here that the thieno-TZD (+)-JQ1, a potent BET inhibitor, strongly stimulated apoA-I production in Hep-G2 cells, but that its enantiomer (-)-JQ1, which has no BET inhibitor activity, also showed considerable effect on apoA-I production. MDCO-3770 and MDCO-3783 also inhibited BRD3 and BRD4 in vitro, with potency somewhat below that of (+)-JQ1. We conclude that the effect of thieno-TZDs on apoA-I expression is not due to inhibition of the BZD or PAF receptors and is not completely explained by transcriptional repression by BET proteins.

  19. Development and Validation of an Instrument to Assess Social Work Students&apos; Perceptions, Knowledge, and Attitudes about Human Trafficking Questionnaire (PKA-HTQ): An Exploratory Study (United States)

    Nsonwu, Maura Busch; Welch-Brewer, Chiquitia; Heffron, Laurie Cook; Lemke, Melinda A.; Busch-Armendariz, Noel; Sulley, Caitlin; Cook, Sharon Warren; Lewis, Mary; Watson, Elizabeth; Moore, Wayne; Li, Jilan


    Objective: This study sought to develop and evaluate the psychometric properties of a tool designed to assess social work students' knowledge of and perceptions and attitudes toward human trafficking. To achieve this aim, the Perceptions, Knowledge, and Attitudes toward Human Trafficking Questionnaire (PKA-HTQ) was developed and its psychometric…

  20. Differential interaction of Apolipoprotein-E isoforms with insulin receptors modulates brain insulin signaling in mutant human amyloid precursor protein transgenic mice. (United States)

    Chan, Elizabeth S; Chen, Christopher; Cole, Gregory M; Wong, Boon-Seng


    It is unclear how human apolipoprotein E4 (ApoE4) increases the risk for Alzheimer's disease (AD). Although Aβ levels can lead to insulin signaling impairment, these experiments were done in the absence of human ApoE. To examine ApoE role, we crossed the human ApoE-targeted replacement mice with mutant human amyloid precursor protein (APP) mice. In 26 week old mice with lower Aβ levels, the expression and phosphorylation of insulin signaling proteins remained comparable among APP, ApoE3xAPP and ApoE4xAPP mouse brains. When the mice aged to 78 weeks, these proteins were markedly reduced in APP and ApoE4xAPP mouse brains. While Aβ can bind to insulin receptor, how ApoE isoforms modulate this interaction remains unknown. Here, we showed that ApoE3 had greater association with insulin receptor as compared to ApoE4, regardless of Aβ42 concentration. In contrast, ApoE4 bound more Aβ42 with increasing peptide levels. Using primary hippocampal neurons, we showed that ApoE3 and ApoE4 neurons are equally sensitive to physiological levels of insulin. However, in the presence of Aβ42, insulin failed to elicit a downstream response only in ApoE4 hippocampal neurons. Taken together, our data show that ApoE genotypes can modulate this Aβ-mediated insulin signaling impairment.

  1. Structural consequences of binding of UO{sub 2}{sup 2+} to apo-transferrin: Can this protein account for entry of uranium into human cells?

    Energy Technology Data Exchange (ETDEWEB)

    Vidaud, C [CEA Valrho, DSV, DIEP, Service de Biochimie Post Genomique and Toxicologie Nucleaire, F-30207 Bagnols Sur Ceze (France); Vidaud, C.; Gourion-Arsiquaud, S; Rollin-Genetet, F; Torne-Celer, C; Plantevin, S; Pible, O; Quemeneur, E; Berthomieu, C. [CEA Cadarache, Laboratoire de Bioenergetique Cellulaire and Laboratoire des Interactions Proteine-Metal, DSV/DEVM, UMR 6191 CNRS-CEA-Universite Aix-Marseille II, F-13108 Saint-Paul-lez-Durance Cedex (France)


    It has been established that transferrin binds a variety of metals. These include toxic uranyl ions which form rather stable uranyl-transferrin derivatives. We determined the extent to which the iron binding sites might accommodate the peculiar topographic profile of the uranyl ion and the consequences of its binding on protein conformation. Indeed, metal intake via endocytosis of the transferrin/transferrin receptor depends on the adequate coordination of the metal in its site, which controls protein conformation and receptor binding. Using UV-vis and Fourier transform infrared difference spectroscopy coupled to a micro-dialysis system, we showed that at both metal binding sites two tyrosines are uranyl ligands, while histidine does not participate with its coordination sphere. Analysis by circular dichroism and differential scanning calorimetry (DSC) showed major differences between structural changes associated with interactions of iron or uranyl with apo-transferrin. Uranyl coordination reduces the level of protein stabilization compared to iron, but this may be simply related to partial lobe closure. The lack of interaction between uranyl-TF and its receptor was shown by flow cytometry using Alexa 488-labeled holo-transferrin. We propose a structural model summarizing our conclusion that the uranyl-TF complex adopts an open conformation that is not appropriate for optimal binding to the transferrin receptor. (authors)

  2. Proceedings of the DGMK-conference &apos;Synthesis gas chemistry&apos;. Authors&apos; manuscripts

    Energy Technology Data Exchange (ETDEWEB)

    Hoenicke, D.; Kohlpaintner, C.; Luecke, B.; Reschetilowski, W. [eds.


    The main topics of the DGMK-Conference &apos;&apos;Synthesis Gas Chemistry&apos;&apos; were: production of synthesis gas from several educts, new catalysts, Fischer-Tropsch synthesis, hydroformylation, steam reforming and carbonylation.

  3. Progress Report: DE-FG03-97ER20274, &apos;&apos;Microbial Production of Isoprene&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Ray Fall


    We have discovered that microorganisms produce and emit the hydrocarbon isoprene (2-methyl-1,3-butadiene), and have suggested that if isoprene-producing enzymes and their genes can be harnessed, useful hydrocarbon-producing systems might be constructed. The main goal of the proposed work is to establish the biochemical mechanism and regulation of isoprene formation in the bacterial system, Bacillus subtilis. Specific objectives of the proposed work are the following: (A) to characterize the physiological regulation of isoprene formation in B. subtilis; (B) to characterize mutations in B. subtilis 168 that suppress isoprene formation, clone these genes, and determine how isoprene and isoprenoid carbon flow are regulated; and (C) to test &apos;'overflow'&apos; and &apos;'signaling'&apos; models for Bacillus isoprene formation. We are also pursuing the isolation and cloning of B. subtilis isoprene synthase, which we believe may be a regulatory enzyme.

  4. Design and implementation of a &apos;'cheese'&apos; phantom-based Tomotherapy TLD dose intercomparison

    Energy Technology Data Exchange (ETDEWEB)

    Schiefer, Hans; Buchauer, Konrad; Heinze, Simon [Medical Physics Group, Department of Radiation Oncology, St. Gallen (Switzerland); Henke, Guido; Plasswilm, Ludwig [Department of Radiation Oncology, St. Gallen (Switzerland)


    The unique beam-delivery technique of Tomotherapy machines (Accuray Inc., Sunnyvale, Calif.) necessitates tailored quality assurance. This requirement also applies to external dose intercomparisons. Therefore, the aim of the 2014 SSRMP (Swiss Society of Radiobiology and Medical Physics) dosimetry intercomparison was to compare two set-ups with different phantoms. A small cylindrical Perspex phantom, which is similar to the IROC phantom (Imaging and Radiation Oncology Core, Houston, Tex.), and the &apos;'cheese'&apos; phantom, which is provided by the Tomotherapy manufacturer to all institutions, were used. The standard calibration plans for the TomoHelical and TomoDirect irradiation techniques were applied. These plans are routinely used for dose output calibration in Tomotherapy institutions. We tested 20 Tomotherapy machines in Germany and Switzerland. The ratio of the measured (D{sub m}) to the calculated (D{sub c}) dose was assessed for both phantoms and irradiation techniques. The D{sub m}/D{sub c} distributions were determined to compare the suitability of the measurement set-ups investigated. The standard deviations of the TLD-measured (thermoluminescent dosimetry) D{sub m}/D{sub c} ratios for the &apos;'cheese'&apos; phantom were 1.9 % for the TomoHelical (19 measurements) and 1.2 % (11 measurements) for the TomoDirect irradiation techniques. The corresponding ratios for the Perspex phantom were 2.8 % (18 measurements) and 1.8 % (11 measurements). Compared with the Perspex phantom-based set-up, the &apos;'cheese'&apos; phantom-based set-up without individual planning was demonstrated to be more suitable for Tomotherapy dose checks. Future SSRMP dosimetry intercomparisons for Tomotherapy machines will therefore be based on the &apos;'cheese'&apos; phantom set-up. (orig.) [German] Die einzigartige Bestrahlungstechnik mit Tomotherapie-Bestrahlungsgeraeten (Accuray Inc., Sunnyvale, CA, USA) erfordert spezifische

  5. In situ AFM imaging of apolipoprotein A-I directly derived from plasma HDL. (United States)

    Gan, Chaoye; Wang, Zhexuan; Chen, Yong


    The major apolipoproteins of plasma lipoproteins play vital roles in the structural integrity and physiological functions of lipoproteins. More than ten structural models of apolipoprotein A-I (apoA-I), the major apolipoprotein of high-density lipoprotein (HDL), have been developed successively. In these models, apoA-I was supposed to organize in a ring-shaped form. To date, however, there is no direct evidence under physiological condition. Here, atomic force microscopy (AFM) was used to in situ visualize the organization of apoA-I, which was exposed via depletion of the lipid component of plasma HDL pre-immobilized on functionalized mica sheets. For the first time, the ring-shaped coarse structure and three detailed structures (crescent-shaped, gapped "O"-shaped, and parentheses-shaped structures, respectively) of apoA-I in plasma HDL, which have the ability of binding scavenger receptors, were directly observed and quantitatively measured by AFM. The three detailed structures probably represent the different extents to which the lipid component of HDL was depleted. Data on lipid depletion of HDL may provide clues to understand lipid insertion of HDL. These data provide important information for the understanding of the structure/maturation of plasma HDL. Moreover, they suggest a powerful method for directly visualizing the major apolipoproteins of plasma lipoproteins or the protein component of lipoprotein-like lipid-protein complexes. Copyright © 2017 Elsevier B.V. All rights reserved.


    Energy Technology Data Exchange (ETDEWEB)

    Casadei, Diego, E-mail: [Visiting Scientist, Department of Physics and Astronomy, UCL, Gower Street, London WC1E 6BT (United Kingdom)


    In high-energy astrophysics, it is common practice to account for the background overlaid with counts from the source of interest with the help of auxiliary measurements carried out by pointing off-source. In this &apos;'on/off'&apos; measurement, one knows the number of photons detected while pointing toward the source, the number of photons collected while pointing away from the source, and how to estimate the background counts in the source region from the flux observed in the auxiliary measurements. For very faint sources, the number of photons detected is so low that the approximations that hold asymptotically are not valid. On the other hand, an analytical solution exists for the Bayesian statistical inference, which is valid at low and high counts. Here we illustrate the objective Bayesian solution based on the reference posterior and compare the result with the approach very recently proposed by Knoetig, and discuss its most delicate points. In addition, we propose to compute the significance of the excess with respect to the background-only expectation with a method that is able to account for any uncertainty on the background and is valid for any photon count. This method is compared to the widely used significance formula by Li and Ma, which is based on asymptotic properties.

  7. Formation and characterisation of solution processed &apos;'pseudo-bilayer'&apos; organic solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Heinemann, Marc Daniel; Ananthanarayanan, Krishnamoorthy; Thummalakunta, L.N.S.A.; Yong, Chian Haw; Luther, Joachim [Singapore National Univ. (SG). Solar Energy Research Inst. of Singapore (SERIS)


    The current state of the art solution processed organic photovoltaic (OPV) cells are based on the bulk heterojunction (BHJ) architecture, consisting of an active layer, in which the donor and the acceptor material are dissolved in a common solvent. In this report, we show that by sequential processing of the active components and by subsequent annealing a &apos;'pseudo-bilayer'&apos; can be formed which results in an enhanced nanomorphology for efficient charge generation and extraction. The enhanced nanomorphology arises from the inter-diffusion of the PCBM nanoparticles into a layer of pre-organised polymer P3HT instead of a phase separation that happens at the time of spin-coating and annealing in the case of conventional BHJ devices. To get a further insight into the inter-diffusion process, TOF-SIMS depth profiling and XPS measurements were carried out for different thermal annealing treatments of these pseudo-bilayer devices, which show full inter-diffusion after only seconds of annealing at 140 C. The optimised photovoltaic devices that were fabricated showed an efficiency of 4.1%. (orig.)

  8. &apos;&apos;1/f noise&apos;&apos; in music: Music from 1/f noise

    Energy Technology Data Exchange (ETDEWEB)

    Voss, R.F.; Clarke, J.


    The spectral density of fluctuations in the audio power of many musical selections and of English speech varies approximately as 1/f (f is the frequency) down to a frequency of 5 x 10/sup -4/ Hz. This result implies that the audio-power fluctuations are correlated over all times in the same manner as &apos;&apos;1/f noise&apos;&apos; in electronic components. The frequency fluctuations of music also have a 1/f spectral density at frequencies down to the inverse of the length of the piece of music. The frequency fluctuations of English speech have a quite different behavior, with a single characteristic time of about 0.1 s, the average length of a syllable. The observations on music suggest that 1/f noise is a good choice for stochastic composition. Compositions in which the frequency and duration of each note were determined by 1/f noise sources sounded pleasing. Those generated by white-noise sources sounded too random, while those generated by 1/f/sup 2/ noise sounded too correlated.

  9. Study and designing of the &apos;'caliprax'&apos; measurement bench; Etude et realisation du banc &apos;'caliprax'&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Barriere, J.Ch


    Probing the matter in order to check its elementary constituents, that is the goal of the particle physic. In this field, the experiments consist in colliding highly energetic particle beams and observing the new born particles. These observations are based on big particle detectors whose running is dependant on the precise knowledge of their geometry (position of the detection chambers). To achieve this, the detectors are equipped with alignment sensors, which have to be calibrated before. This document describes the study and the making of a calibration bench for the &apos;Praxial&apos; (PRoximity AXIAL) type sensors, and other works related to these sensors. In a first part, we determine and apply a method to set the tools used to fix the sensor stands on the detection chambers. These settings are made with the use of a tridimensional measuring machine. Then, we study the stands themselves. These investigations concern mechanics: positioning quality of the sensors in their stands, bending of the supports due to the tightening. In this part too, the studies are in the field of dimensional metrology. After this, the works are reoriented toward the bench, with the choice of the displacement sensors among two different technologies: optical, with the Rasnik system, and mechanical, with linear probes as LVDT (Linear Variable Differential Transformer). Following the discovery of an ambiguity on the Rasnik system, we go on the tests to understand its behaviour. We introduce the theory of the alignment sensors calibration, which is based on a minimization calculation. The computer programs are explained in a chapter, and in an other, the implementation of the quality assurance procedures. An other part describes the mechanical studies and the problems they cause. Because of a delay onset of the project, we make a model of the bench. This dummy allows us to test every single function of the final bench. With this device, we record manually the first calibration data and

  10. Magnetic fluctuations can contribute to plasma transport, &apos;&apos;self-consistency constraints&apos;&apos; notwithstanding

    Energy Technology Data Exchange (ETDEWEB)

    Krommes, J.A.; Kim, Chang-Bae


    The recent conclusion that in a turbulent, collisionless plasma &apos;&apos;magnetic transport including quasilinear magnetic flutter transport ... does not contribute to the relaxation of (f), and thus is not responsible for electron energy or momentum transport&apos;&apos; is shown to be incorrect for a variety of situations of physical interest, including saturation by quasilinear plateau formation, induced scattering, and, most importantly, conventional mode coupling. The well-established theory of the mean infinitesimal response function and the spectral balance equation provides a unifying framework for understanding the above conclusion. In particular, the cancellations which lead to their conclusion are special cases of well-known relationships between the response function, particle propagator, and dielectric function. A more general, concise, and manifestly gauge-invariant algebraic derivation of the cancellations is given. Though the cancellations occur in a certain limit, these conclusions do not follow in general: The picture of steady-state turbulence as consisting of small-scale &apos;'incoherent'&apos; ballistic &apos;'clumps'&apos; shielded by long-wavelength &apos;'coherent'&apos; dielectric response is physically misleading and mathematically incomplete, as it ignores or mistreates the often dominant process of renormalized n-wave coupling. Thus, when ion nonlinearities are considered, formulas for the magnetic contribution to transport emerge which are quite similar to the quasilinear one. Furthermore, limits are possible in which all or part of the noise can be negligible, yet in which the total fluctuation spectrum remains finite. 56 refs.

  11. Calculation of Mossbauer paramagnetic relaxation spectra without the &apos;&apos;White-Noise approximation&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Shenoy, G.K.; Dunlap, B.D.; Dattagupta, S.; Asch, L.


    Theoretical expressions have been obtained for calculating Mossbauer paramagnetic relaxation line shapes without involving the &apos;&apos;white-noise approximation.&apos;&apos; The relaxation matrix is shown to be dependent on the hyperfine parameters and linewidth in addition to the bath parameters. The theory is used to analyze the data for Cs/sub 2/NaYbCl/sub 6/ and obtain values for the mean-square dipolar field and the spin correlaton time. (AIP)

  12. Absorption-line &apos;'forest'&apos; in quasar spectra, and the structure of the universe

    Energy Technology Data Exchange (ETDEWEB)

    Doroshkevich, A.G.; Muket, J.P.


    The &apos;'forest'&apos; of absorption lines observed in the spectrum of distant quasars is interpreted in light of the adiabatic (pancake) theory for the origin and evolution of structure in the universe. The hidden mass might reside in neutrino-like particles (perhaps unstable) having a rest mass of about 60--100 eV. Opportunities for testing the hypothesis observationally are discussed.

  13. In vivo imaging of &apos;'neuroinflammation'&apos;. Principles and applications; In-vivo-Darstellung &apos;'neuroinflammatorischer'&apos; Veraenderungen mit [{sup 11}C] PK11195-PET. Grundlagen und Anwendung

    Energy Technology Data Exchange (ETDEWEB)

    Gerhard, A.; Banati, R.B. [MRC Clinical Sciences Centre and Div. of Neuroscience, Faculty of Medicine, Imperial Coll., London (United Kingdom)


    Microglia are the brains&apos; resident immunocompetent cells that can be activated by acute as well as chronic pathological stimuli. When activated they express the peripheral benzodiazepine binding site to which the isoquinolin PK11195 binds with high specificity. Labelled with [{sup 11}C], the R-enatiomer [{sup 11}C] PK1195 has been used for positron emission tomography (PET) studies to demonstrate neuroinflammatory changes in vivo. [{sup 11}C](R) PK11195-PET has been successfully used to show in vivo microglial activation in ischemic (stroke), inflammatory (multiple sclerosis) and degenerative (Alzheimer&apos;s and Parkinson&apos;s disease). Longitudinal studies are in progress to help to clarify the relationship between localisation and extent of microglial activation and the clinical presentations in these disorders. This will help to determine the role of [{sup 11}C](R) PK11195 PET as a diagnostic tool and a surrogate marker of &apos;'neuroinflammation'&apos; in therapeutic trials. (orig.) [German] Mikroglia sind residente immunkompetente Zellen des Gehirns, die durch akute, aber auch langsam voranschreitende, chronische Schaedigungprozesse aktiviert werden. Im aktivierten Zustand exprimieren sie den peripheren Benzodiazepinrezeptor, an den das Isoquinolin PK11195 spezifisch bindet. Radioaktiv markiert kann das R-Enantiomer [{sup 11}C] PK11195 als Ligand in der Positronenemissionstomographie (PET) genutzt werden und ermoeglicht so die In-vivo-Darstellung aktiver &apos;'neuroinflammatorischer'&apos;, d.h. die Mikroglia aktivierender, Veraenderungen. Mit der [{sup 11}C](R) PK11195-PET konnte bisher In-vivo-Mikrogliaaktivierung bei ischaemischen (Schlaganfall), entzuendlichen (multiple Sklerose) und degenerativen (Morbus Alzheimer- und Parkinson-Erkrankung) demonstriert werden. Laufende longitudinale Studien werden dazu beitragen, die Beziehung zwischen Lokalisation und Ausmass der Mikrogliaaktivierung und klinischer Krankheitsauspraegung

  14. Zebrafish as a model for apolipoprotein biology: comprehensive expression analysis and a role for ApoA-IV in regulating food intake

    Directory of Open Access Journals (Sweden)

    Jessica P. Otis


    Full Text Available Improved understanding of lipoproteins, particles that transport lipids throughout the circulation, is vital to developing new treatments for the dyslipidemias associated with metabolic syndrome. Apolipoproteins are a key component of lipoproteins. Apolipoproteins are proteins that structure lipoproteins and regulate lipid metabolism through control of cellular lipid exchange. Constraints of cell culture and mouse models mean that there is a need for a complementary model that can replicate the complex in vivo milieu that regulates apolipoprotein and lipoprotein biology. Here, we further establish the utility of the genetically tractable and optically clear larval zebrafish as a model of apolipoprotein biology. Gene ancestry analyses were implemented to determine the closest human orthologs of the zebrafish apolipoprotein A-I (apoA-I, apoB, apoE and apoA-IV genes and therefore ensure that they have been correctly named. Their expression patterns throughout development were also analyzed, by whole-mount mRNA in situ hybridization (ISH. The ISH results emphasized the importance of apolipoproteins in transporting yolk and dietary lipids: mRNA expression of all apolipoproteins was observed in the yolk syncytial layer, and intestinal and liver expression was observed from 4–6 days post-fertilization (dpf. Furthermore, real-time PCR confirmed that transcription of three of the four zebrafish apoA-IV genes was increased 4 hours after the onset of a 1-hour high-fat feed. Therefore, we tested the hypothesis that zebrafish ApoA-IV performs a conserved role to that in rat in the regulation of food intake by transiently overexpressing ApoA-IVb.1 in transgenic larvae and quantifying ingestion of co-fed fluorescently labeled fatty acid during a high-fat meal as an indicator of food intake. Indeed, ApoA-IVb.1 overexpression decreased food intake by approximately one-third. This study comprehensively describes the expression and function of eleven zebrafish

  15. Traveling Chaucer: Comparative Translation and Cosmopolitan Humanism (United States)

    Barrington, Candace


    Through the comparative study of non-Anglophone translations of Geoffrey Chaucer&apos;s "The Canterbury Tales," we can achieve the progressive goals of Emily Apter&apos;s "translational transnationalism" and Edward Said&apos;s "cosmopolitan humanism." Both translation and humanism were intrinsic to Chaucer&apos;s…

  16. Traveling Chaucer: Comparative Translation and Cosmopolitan Humanism (United States)

    Barrington, Candace


    Through the comparative study of non-Anglophone translations of Geoffrey Chaucer&apos;s "The Canterbury Tales," we can achieve the progressive goals of Emily Apter&apos;s "translational transnationalism" and Edward Said&apos;s "cosmopolitan humanism." Both translation and humanism were intrinsic to Chaucer&apos;s…

  17. Room temperature ferromagnetic-like response in &apos;'bulk'&apos; Y-doped CeO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Rakhmatullin, R.M. [Institute of Physics, Kazan Federal University, Kremlevskaya 18, 420008 Kazan (Russian Federation); Sen, S. [Department of Materials Science and Engineering, University of California at Davis, Davis, CA 95616 (United States)


    Strong ferromagnetic-like response is observed at room temperature in &apos;'bulk'&apos;- and nano-crystalline Y-doped CeO{sub 2}. The saturation magnetization for &apos;'bulk'&apos; (∝600 nm) crystallites of CeO{sub 2} doped with 25 at.% Y is more than an order of magnitude higher compared to its nanocrystalline (∝10 nm) counterpart. High frequency electron spin resonance and {sup 89}Y nuclear magnetic resonance measurements indicate clustering of electronic defects in the &apos;'bulk'&apos; crystallites. The remarkable size dependence of the magnetic behavior likely originates from a collective magnetic response of defect-lined nanodomain interfaces in the &apos;'bulk'&apos; crystallites, consistent with the giant orbital paramagnetism model. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  18. Reduction of the immunostainable length of the hippocampal dentate granule cells&apos; primary cilia in 3xAD-transgenic mice producing human A{beta}{sub 1-42} and tau

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarthy, Balu, E-mail: [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); Gaudet, Chantal; Menard, Michel; Brown, Leslie; Atkinson, Trevor [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); LaFerla, Frank M. [Department of Neurobiology and Behavior, University of California, Irvine, CA (United States); Ito, Shingo [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); Armato, Ubaldo; Dal Pra, Ilaria [Department of Life and Reproduction Sciences, University of Verona Medical School, Verona (Italy); Whitfield, James [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada)


    Highlights: Black-Right-Pointing-Pointer A{beta} and tau-induced neurofibrillary tangles play a key role in Alzheimer&apos;s disease. Black-Right-Pointing-Pointer A{beta}{sub 1-42} and mutant tau protein together reduce the primary cilium length. Black-Right-Pointing-Pointer This shortening likely reduces cilium-dependent neurogenesis and memory function. Black-Right-Pointing-Pointer This provides a model of an A{beta}/tau targeting of a neuronal signaling organelle. -- Abstract: The hippocampal dentate gyrus is one of the two sites of continuous neurogenesis in adult rodents and humans. Virtually all dentate granule cells have a single immobile cilium with a microtubule spine or axoneme covered with a specialized cell membrane loaded with receptors such as the somatostatin receptor 3 (SSTR3), and the p75 neurotrophin receptor (p75{sup NTR}). The signals from these receptors have been reported to stimulate neuroprogenitor proliferation and the post-mitotic maturation of newborn granule cells into functioning granule cells. We have found that in 6-24-months-old triple transgenic Alzheimer&apos;s disease model mice (3xTg-AD) producing both A{beta}{sub 1-42} and the mutant human tau protein tau{sub P301L,} the dentate granule cells still had immunostainable SSTR3- and p75{sup NTR}-bearing cilia but they were only half the length of the immunostained cilia in the corresponding wild-type mice. However, the immunostainable length of the granule cell cilia was not reduced either in 2xTg-AD mice accumulating large amounts of A{beta}{sub 1-42} or in mice accumulating only a mutant human tau protein. Thus it appears that a combination of A{beta}{sub 1-42} and tau protein accumulation affects the levels of functionally important receptors in 3xTg-AD mice. These observations raise the important possibility that structural and functional changes in granule cell cilia might have a role in AD.

  19. &apos;&apos;Whither Deterrence?&apos;&apos; A Brief Synopsis May, 2002

    Energy Technology Data Exchange (ETDEWEB)

    Poppe, C; Vergino, E; Barker, R; Brown, P; Gilmartin, T J; Nach, M; Sloss, L


    To most audiences, deterrence has been interconnected with nuclear weapons whose purpose had been to deter a Soviet attack. But, the Soviet Union has been gone for almost a decade. President George W. Bush has stated that Russia is not an enemy of the US and the numbers of nuclear weapons can be dramatically reduced. It is important to note that deterrence has always transcended nuclear weapons. The US&apos; first line of deterrence has been its formidable conventional warfare capability, designed to prevent conflict and win wars if necessary. The role of nuclear weapons has been to deter the,use of nuclear weapons and other weapons of mass destruction against U.S. interests during the conduct of conventional warfare and to ensure our ability to inflict massive destruction on any who would use nuclear weapons, or other weapons of mass destruction, against us. With regard to the Soviet Union, the threat of the use of nuclear weapons was a critical component of our deterrent to prevent massive Soviet conventional attack against our allies in Europe. However, the events of September 11, 2001 make clear that we have not convinced all who seek to harm us that we will be able to respond in a manner to make them wish they had not even tried. The September 11 attacks, as well as other past conflicts, do not mean that deterrence has failed-it remains effective against the threats for which it was designed. We have known there are other threats for which we did not have a credible deterrent. The challenge is to sustain deterrence against the classic threats as they evolve in technical sophistication while remaining alert to the need to evaluate continuously our ability to deter previously unforeseen challenges. How then should we be looking at deterrence as we consider fifteen or so years in the future, say to about 2015? What will be the role of nuclear weapons and other instruments of mass destruction in the future? What should the US be doing to prepare for the future? In

  20. &apos;&apos;Whither Deterrence?&apos;&apos; A Brief Synopsis May, 2002

    Energy Technology Data Exchange (ETDEWEB)

    Poppe, C; Vergino, E; Barker, R; Brown, P; Gilmartin, T J; Nach, M; Sloss, L


    To most audiences, deterrence has been interconnected with nuclear weapons whose purpose had been to deter a Soviet attack. But, the Soviet Union has been gone for almost a decade. President George W. Bush has stated that Russia is not an enemy of the US and the numbers of nuclear weapons can be dramatically reduced. It is important to note that deterrence has always transcended nuclear weapons. The US&apos; first line of deterrence has been its formidable conventional warfare capability, designed to prevent conflict and win wars if necessary. The role of nuclear weapons has been to deter the,use of nuclear weapons and other weapons of mass destruction against U.S. interests during the conduct of conventional warfare and to ensure our ability to inflict massive destruction on any who would use nuclear weapons, or other weapons of mass destruction, against us. With regard to the Soviet Union, the threat of the use of nuclear weapons was a critical component of our deterrent to prevent massive Soviet conventional attack against our allies in Europe. However, the events of September 11, 2001 make clear that we have not convinced all who seek to harm us that we will be able to respond in a manner to make them wish they had not even tried. The September 11 attacks, as well as other past conflicts, do not mean that deterrence has failed-it remains effective against the threats for which it was designed. We have known there are other threats for which we did not have a credible deterrent. The challenge is to sustain deterrence against the classic threats as they evolve in technical sophistication while remaining alert to the need to evaluate continuously our ability to deter previously unforeseen challenges. How then should we be looking at deterrence as we consider fifteen or so years in the future, say to about 2015? What will be the role of nuclear weapons and other instruments of mass destruction in the future? What should the US be doing to prepare for the future? In

  1. Sex Differences in Presynaptic Density and Neurogenesis in Middle-Aged ApoE4 and ApoE Knockout Mice

    Directory of Open Access Journals (Sweden)

    A. Rijpma


    Full Text Available Atherosclerosis and apolipoprotein E ε4 (APOE4 genotype are risk factors for Alzheimer’s disease (AD and cardiovascular disease (CVD. Sex differences exist in prevalence and manifestation of both diseases. We investigated sex differences respective to aging, focusing on cognitive parameters in apoE4 and apoE knockout (ko mouse models of AD and CVD. Presynaptic density and neurogenesis were investigated immunohistochemically in male and female apoE4, apoE ko, and wild-type mice. Middle-aged female apoE4 mice showed decreased presynaptic density in the inner molecular layer of the dentate gyrus of the hippocampus. Middle-aged female apoE ko mice showed a trend towards increased neurogenesis in the hippocampus compared with wild-type mice. No differences in these parameters could be observed in middle-aged male mice. Specific harmful interactions between apoE4 and estrogen could be responsible for decreased presynaptic density in female apoE4 mice. The trend of increased neurogenesis found in female apoE ko mice supports previous studies suggesting that temporarily increased amount of synaptic contacts and/or neurogenesis is a compensatory mechanism for synaptic failure. To our knowledge, no other studies investigating presynaptic density in aging female apoE4 or apoE ko mice are available. Sex-specific differences between APOE genotypes could account for some sex differences in AD and CVD.

  2. VEGF Mediates ApoE4-Induced Neovascularization and Synaptic Pathology in the Choroid and Retina. (United States)

    Antes, Ran; Salomon-Zimri, Shiran; Beck, Susanne C; Garcia Garrido, Marina; Livnat, Tami; Maharshak, Idit; Kadar, Tamar; Seeliger, Mathias; Weinberger, Dov; Michaelson, Daniel M


    Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with neuronal and vascular impairments. Recent findings suggest that retina of apoE4 mice have synaptic and functional impairments. We presently investigated the effects of apoE4 on retinal and choroidal vasculature and the possible role of VEGF in these effects. There were no histological differences between the retinal and choroidal vasculatures of naïve apoE3 and apoE4 mice. In contrast, laserdriven choroidal injury induced higher levels of choroidal neovascularization (CNV) in apoE4 than in apoE3 mice. These effects were associated with an inflammatory response and with activation of the Muller cells and asrocytic markers gluthatione synthetase and GFAP, all of which were more pronounced in the apoE4 mice. CNV also induced a transient increase in the levels of the synaptic markers synaptophysin and PSD95 which were however similar in the apoE4 and apoE3 naive mice. Retinal and choroidal VEGF and apoE levels were lower in naïve apoE4 than in corresponding apoE3 mice. In contrast, VEGF and apoE levels rose more pronouncedly following laser injury in the apoE4 than in apoE3 mice. Taken together, these findings suggest that the apoE4-induced retinal impairments, under basal conditions, may be related to reduced VEGF levels in the eyes of these mice. The hyper-neovascularization in the apoE4 mice might be driven by increased inflammation and the associated surge in VEGF following injury. Retinal and choroidal VEGF and apoE levels were lower in naïve apoE4 than in corresponding apoE3 mice. In contrast, VEGF and apoE levels rose more pronouncedly following laser injury in the apoE4 than in apoE3 mice. Taken together, these findings suggest that the apoE4-induced retinal impairments, under basal conditions, may be related to reduced VEGF levels in the eyes of these mice. The hyper-neovascularization in the apoE4 mice might be driven by increased inflammation

  3. High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Gordon


    Full Text Available Apolipoprotein A-I (apoA-I and high-density lipoproteins (HDL mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol efflux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury, asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia. Similar to observations in cardiovascular disease, however, HDL may become dysfunctional and contribute to disease pathogenesis in respiratory disorders. Furthermore, synthetic apoA-I mimetic peptides have been shown to have protective effects in animal models of acute lung injury, asthma, pulmonary hypertension, and influenza pneumonia. These findings provide evidence to support the concept that apoA-I mimetic peptides might be developed into a new treatment that can either prevent or attenuate the manifestations of lung diseases, such as asthma. Thus, the lung is positioned to take a page from the cardiovascular disease playbook and utilize the protective properties of HDL and apoA-I as a novel therapeutic approach.

  4. &apos;'Routine'&apos; brain CT in psychiatric patients - does it make sense?; &apos;'Routine'&apos;-Schaedel-CT in der psychiatrischen Diagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Pickuth, D.; Heywang-Koebrunner, S.H.; Spielmann, R.P. [Martin-Luther-Universitaet Halle-Wittenberg, Halle (Germany). Klinik und Poliklinik fuer Diagnostische Radiologie


    Purpose: To prospectively assess the spectrum of brain CT findings in psychiatric patients and to determine the number of patients that had an underlying cause for the symptoms. Patients and methods: Over a period of six months, 142 patients (78 males, 64 females; median age 61 [18-91] years) were referred for CT brain scans. Their scans were reviewed, along with the clinical information that was provided in the request form. All the hard copies were reviewed to assess areas of ischaemia, infarction, atrophy, tumours, and haematomas. The majority of requests were to exclude vascular event or space-occupying lesions. Clinical indications included mood disorders (depression, mania), schizophrenic disorders, dementia, personality and behavioural disorders. Results: 31 (22%) were normal. 111 (78%) had varying degrees of ischaemia, infarction and cerebral/cerebellar atrophy. 7 (4.9%) had space-occupying lesions which included two gliomas and five meningiomas. There were two chronic subdural haematomas and one arteriovenous malformation. Conclusion: 1. In our series, pathologic findings in &apos;routine&apos; brain CT&apos;s were encountered in 78%. 2. The incidence of brain tumours was 4.9%, compared with 0.00005% of the general population. 3. CT scanning in psychiatric patients is cost-effective and especially indicated when there is an atypical presentation, or inadequate response to standard treatment. (orig.) [German] Hintergrund: Bei psychiatrischen Patienten wird vielerorts routinemaessig eine kraniale Computertomographie (CCT) durchgefuehrt. Ob der Nutzen die Kosten rechtfertigt, wurde im Rahmen einer Prospektivstudie untersucht. Patienten und Methode: In einem Zeitraum von 6 Monaten wurde bei 142 psychiatrischen Patienten (78 Maenner, 64 Frauen, 18-91 Jahre, Median 61 Jahre) ein CCT angefertigt. Die Untersuchung erfolgt nativ in 5-mm-Schichtdicke, bei klinischem Verdacht auf eine intrakraniale Raumforderung auch kontrastverstaerkt. Ueberweisungsdiagnosen waren v

  5. Extended-release niacin alters the metabolism of plasma apolipoprotein (apo) A-I- and apoB-containing lipoproteins (United States)

    Extended-release niacin effectively lowers plasma TG levels and raises plasma HDL cholesterol levels, but the mechanisms responsible for these effects are unclear. We examined the effects of extended-release niacin (2 g/d) and extended-release niacin (2 g/d) plus lovastatin (40 mg/d), relative to pl...

  6. The plasma concentration of HDL-associated apoM is influenced by LDL receptor-mediated clearance of apoB-containing particles

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Benn, Marianne; Christensen, Pernille Møller;


    are affected by the rate of LDL receptor-mediated clearance of apoB-containing particles. We measured apoM in humans each carrying one of three different LDL receptor mutations (n = 9) or the apoB3500 mutation (n = 12). These carriers had increased plasma apoM (1.34 ± 0.13 µM, P = 0.003, and 1.23 ± 0.10 µM, P...... catabolic rate of LDL (r = -0.38, P = 0.009). These data suggest that the plasma clearance of apoM, despite apoM primarily being associated with HDL, is influenced by LDL receptor-mediated clearance of apoB-containing particles....

  7. LLNL&apos;s Big Science Capabilities Help Spur Over $796 Billion in U.S. Economic Activity Sequencing the Human Genome

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, Jeffrey S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)


    LLNL’s successful history of taking on big science projects spans beyond national security and has helped create billions of dollars per year in new economic activity. One example is LLNL’s role in helping sequence the human genome. Over $796 billion in new economic activity in over half a dozen fields has been documented since LLNL successfully completed this Grand Challenge.

  8. Total eco-monitoring system &apos;EcoEASIEST&apos; using a wireless network; Flexible musen network ni yoru &apos;sogo eko kanshi system&apos; &apos;EcoEASIEST&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Ando, N.; Fukuda, E.; Yamamo, H. [Fuji Electric Co. Ltd., Tokyo (Japan)


    Fuji Electric&apos;s total eco-monitoring system mainly consists of analysis, computerization, and transmission. The design concept is &apos;consideration to the field,&apos; &apos;a serviceable database,&apos; and &apos;a flexible network.&apos; This is an optimum system to minimize environmental degradation and reduce energy consumption stated in the ISO14001 and the amendment to the Energy Saving Act. (author)


    Energy Technology Data Exchange (ETDEWEB)

    Ciolfi, Riccardo [Physics Department, University of Trento, Via Sommarive 14, I-38123 Trento (Italy); Siegel, Daniel M., E-mail:, E-mail: [Max Planck Institute for Gravitational Physics (Albert Einstein Institute), Am Mühlenberg 1, D-14476 Potsdam-Golm (Germany)


    Short gamma-ray bursts (SGRBs) are among the most luminous explosions in the universe and their origin still remains uncertain. Observational evidence favors the association with binary neutron star or neutron star-black hole (NS-BH) binary mergers. Leading models relate SGRBs to a relativistic jet launched by the BH-torus system resulting from the merger. However, recent observations have revealed a large fraction of SGRB events accompanied by X-ray afterglows with durations ∼10{sup 2}-10{sup 5} s, suggesting continuous energy injection from a long-lived central engine, which is incompatible with the short (≲ 1 s) accretion timescale of a BH-torus system. The formation of a supramassive NS, resisting the collapse on much longer spin-down timescales, can explain these afterglow durations, but leaves serious doubts on whether a relativistic jet can be launched at the merger. Here we present a novel scenario accommodating both aspects, where the SGRB is produced after the collapse of a supramassive NS. Early differential rotation and subsequent spin-down emission generate an optically thick environment around the NS consisting of a photon-pair nebula and an outer shell of baryon-loaded ejecta. While the jet easily drills through this environment, spin-down radiation diffuses outward on much longer timescales and accumulates a delay that allows the SGRB to be observed before (part of) the long-lasting X-ray signal. By analyzing diffusion timescales for a wide range of physical parameters, we find delays that can generally reach ∼10{sup 5} s, compatible with observations. The success of this fundamental test makes this &apos;'time-reversal'&apos; scenario an attractive alternative to current SGRB models.

  10. Volatile oil prices: two propositions from economics and &apos;'Realpolitik'&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Wirl, F.


    This paper attempts to interpret OPEC&apos;s decision making process by analysing the political-economic behaviour of the Member Countries of the Organization of the Petroleum Exporting Countries. The economic objectives of OPEC members is first discussed under the hypothesis of cooperation versus competition. A loose marketing arrangement among OPEC members is then assumed. Both approaches, pure economics and Real-politik lead to the same conclusion: the likelihood of a volatile price increase.

  11. &apos;&apos;Atomic Optics&apos;&apos;: Nonimaging Optics on the Nanoscale

    Energy Technology Data Exchange (ETDEWEB)

    Roland Winston Joseph O' Gallagher


    This is the final report for a one year close out extension of our basic research program that was established at the University of Chicago more than sixteen years ago to explore and develop the optical sub-discipline that has come to be known as &apos;&apos;nonimaging optics&apos;&apos;. This program has been extremely fruitful, having both broadened the range of formalism available for workers in this field and led to the discovery of many new families of optical devices. These devices and techniques have applications wherever the efficient transport and transformation of light distributions are important, in particular in illumination, fiber optics, collection and concentration of sunlight, and the detection of faint light signals in physics and astrophysics. Over the past thirty years, Nonimaging Optics (Welford and Winston, 1989) has brought a fresh approach to the analysis of many problems in classical macro-scale optics. Through the application of phase-space concepts, statistical methods, thermodynamic arguments, etc., many previously established performance limits were able to be broken and many technical surprises with exciting practical applications were discovered. The most recent three-year phase of our long-term continuing program ended in late 2002 and emphasized extending our work in geometrical optics and expanding it to include some interesting questions in physical optics as well as in the new field of statistical optics. This report presents a survey of the basic history and concepts of nonimaging optics and reviews highlights and significant accomplishments over the past fifteen years. This is followed by a more detailed summary of recent research directions and accomplishments during the last three years. This most recent phase was marked by the broadening in scope to include a separate project involving a collaboration with an industrial partner, Science Applications International Corporation (SAIC). This effort was proposed and approved in

  12. The adductor magnus &apos;'mini-hamstring'&apos;: MRI appearance and potential pitfalls

    Energy Technology Data Exchange (ETDEWEB)

    Broski, Stephen M.; Murthy, Naveen S.; Collins, Mark S. [Department of Radiology, Mayo Clinic, Rochester, MN (United States); Krych, Aaron J. [Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN (United States); Obey, Mitchel R. [Mayo School of Graduate Medical Education, Rochester, MN (United States)


    To examine the anatomic MRI characteristics of the adductor magnus mini hamstring (AMMH) and explore its involvement in cases of hamstring avulsion. An IRB-approved retrospective review of patients undergoing &apos;&apos;hamstring protocol&apos;&apos; MRI between March 2009 and June 2014 was performed. Two musculoskeletal radiologists recorded multiple AMMH anatomic characteristics and involvement in cases of hamstring avulsion. Seventy-six AMMHs were analyzed in 66 patients [35 females and 31 males, mean age 49.3 ± 15.2 years (range 17-81)]. Eleven percent of AMMHs were poorly visualized, 51 % visualized, and 37 % well visualized. Seven percent demonstrated round, 73 % ovoid, and 21 % flat/lenticular tendon morphologies. Most (88 %) demonstrated typical origins. Average cross-sectional area (CSA) was 22.4 ± 10.6 mm{sup 2} (range 6-56), diameter was 7.2 ± 2.5 mm (range 2.9-15), medial distance from the semimembranosus tendon was 7.5 ± 2.5 mm (range 3-14), and tendon length was 6.8 ± 3.3 cm (range 1.2-14.1). There was no gender difference in AMMH anatomic measurements or correlation between age and CSA or diameter. Of 17 complete hamstring avulsion cases, the AMMH was intact in 13, partially torn in 3, and completely torn in 1. The AMMH is a constant finding with variable anatomic characteristics. It is visualized or well visualized by MRI in 88 % of cases and is a sizable tendon located in close proximity to the semimembranosus tendon. Because it is uncommonly completely torn (6 %) in cases of complete hamstring avulsion, radiologists should be aware of its presence and appearance to avoid diagnostic confusion. (orig.)

  13. Report of working committee 3 &apos;&apos;liquefied gases&apos;&apos;; Rapport du comite de travail 3 &apos;&apos;gaz liquefies&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Baudino, M.


    Working Committee 3&apos;s report concerns the evolution of the liquefied gas industry: both liquefied natural gas (LNG) and liquefied petroleum gases (LPG). Given the current state of the LNG market the Committee decided to concentrate on this area in particular. A number of aspects have been identified which the Committee has been looking at, while others have been given to Study Groups set up specifically for the purpose. The first aspects regard: - the development of LNG and LPG, new installations, future chains and relevant statistical data; - the role of LNG and LPG in starting up a gas industry; - operating and technological improvements in the LNG industry; - energy savings, cold utilization and reduction of CO{sub 2} emissions. The Study Groups which were set up dealt with the following subjects: Technological and Economical Developments for cost Reduction of LNG/LPG Facilities. Small Scale LNG Projects and Modular Systems. LNG/LPG Peak Shaving and Satellite Plants. LNG versus Pipeline Infrastructure. (author)

  14. Nothing Human (United States)

    Wharram, C. C.


    In this essay C. C. Wharram argues that Terence&apos;s concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence&apos;s well-known statement "I am a human being--I deem nothing…

  15. Nothing Human (United States)

    Wharram, C. C.


    In this essay C. C. Wharram argues that Terence&apos;s concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence&apos;s well-known statement "I am a human being--I deem nothing…

  16. Extracellular proteolysis of apolipoprotein E (apoE by secreted serine neuronal protease.

    Directory of Open Access Journals (Sweden)

    Irfan Y Tamboli

    Full Text Available Under normal conditions, brain apolipoprotein E (apoE is secreted and lipidated by astrocytes, then taken up by neurons via receptor mediated endocytosis. Free apoE is either degraded in intraneuronal lysosomal compartments or released. Here we identified a novel way by which apoE undergoes proteolysis in the extracellular space via a secreted neuronal protease. We show that apoE is cleaved in neuronal conditioned media by a secreted serine protease. This apoE cleavage was inhibited by PMSF and α1-antichymotrypsin, but not neuroserpin-1 or inhibitors of thrombin and cathepsin G, supporting its identity as a chymotrypsin like protease. In addition, apoE incubation with purified chymotrypsin produced a similar pattern of apoE fragments. Analysis of apoE fragments by mass spectrometry showed cleavages occurring at the C-terminal side of apoE tryptophan residues, further supporting our identification of cleavage by chymotrypsin like protease. Hippocampal neurons were more efficient in mediating this apoE cleavage than cortical neurons. Proteolysis of apoE4 generated higher levels of low molecular weight fragments compared to apoE3. Primary glial cultures released an inhibitor of this proteolytic activity. Together, these studies reveal novel mechanism by which apoE can be regulated and therefore could be useful in designing apoE directed AD therapeutic approaches.

  17. Networks of power: historical power annals, No 2; L&apos;electricite en reseaux - networks of power: annales historiques de l&apos;electricite, No 2

    Energy Technology Data Exchange (ETDEWEB)

    Caron, F.


    In DEcember 2003, the Electricite de France (EdF) foundation and the house of human sciences of Aquitaine organized a colloquium to celebrate the 20. anniversary of the publication from Thomas P. Hughes entitled: &apos;networks of power: electrification in western society 1880-1930&apos;. This book, which has become a major reference, represents a fundamental step in the historiography devoted to electric power history. About 15 specialists from the US and Europe have made a link between their researches and Hughes&apos; theories. The choice of the topics has been made according to the subjects tackled in &apos;Networks of power&apos; but the entire freedom has been given to each participant in the way to treat them. The concepts used by the US searcher have retained the attention, in particular those of &apos;system&apos;, &apos;technological momentum&apos; and &apos;reverse salient&apos;. At the same time, and in order to not limit the analysis of the electric power industry to its technical aspects, several participants have considered also the human, managerial and financial networks aspect. Some others have reexamined Hughes&apos; theories using the present day regulation and deregulation notions. Finally, the same theories have been analyzed considering the complex links between electricity and culture. The publication of the articles of this colloquium is not only a tribute to the great US historian Thomas P. Hughes, but also the opportunity to propose an overview of the richness of the works carried out both in Europe and in the US about the &apos;networks&apos; notion. (J.S.)

  18. RAGE deficiency alleviates aortic valve calcification in ApoE(-/-) mice via the inhibition of endoplasmic reticulum stress. (United States)

    Wang, Bo; Cai, Zhejun; Liu, Baoqing; Liu, Zongtao; Zhou, Xianming; Dong, Nianguo; Li, Fei


    Receptor for advanced glycation end products (RAGE) and endoplasmic reticulum (ER) stress have been shown to be involved in calcific aortic valve disease (CAVD). However, the association between RAGE and ER stress remains unknown in the pathogenesis of CAVD. The current study aims to test the hypothesis that RAGE deficiency alleviates aortic valve calcification via the inhibition of ER stress. Up-regulation of RAGE and ER stress markers in calcified human aortic valves were confirmed by immunoblotting. Aortic valve calcification was evaluated in atherosclerotic prone ApoE(-/-) mice or in mice with dual deficiencies of ApoE and RAGE (ApoE(-/-)RAGE(-/-)) fed with high cholesterol diet for 24weeks. Echocardiography and histological examination show that genetic deficiency of RAGE attenuates aortic valve calcification in ApoE(-/-) mice. Meanwhile, RAGE deficiency inhibited the osteogenic signaling and ER stress activation as well as suppressed macrophage infiltration in vivo. Cultured human aortic valve interstitial cells (AVICs) were treated with high molecular group box 1 protein (HMGB1) as in vitro model. We found that HMGB1 induced osteoblastic differentiation and calcification through RAGE/ER stress. Furthermore, Sox9 up-regulation and intranuclear translocation mediated the pro-osteogenic effect of HMGB1 on AVICs. RAGE or ER stress knockdown reduced the up-regulation of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in human AVICs exposed to HMGB1.These novel findings demonstrate that RAGE deficiency protects against aortic valve calcification in high cholesterol diet-fed ApoE(-/-) mice via inhibition of ER stress. HMGB1 induces AVIC osteoblastic differentiation and calcification through RAGE/ER stress/Sox9 pathway. Copyright © 2016. Published by Elsevier B.V.

  19. Locality or non-locality in quantum mechanics: hidden variables without &apos;&apos;spooky action-at-a-distance&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Aharonov, Y. [Texas A and M Univ., College Station, TX (United States); South Carolina Univ., Columbia, SC (United States). Dept. of Physics and Astronomy; Tel Aviv Univ. (Israel). School of Physics and Astronomy; Botero, A. [South Carolina Univ., Columbia, SC (United States). Dept. of Physics and Astronomy; Centro Internacional de Fisica, Ciudad Univ., Bogota (Colombia); Scully, M. [Texas A and M Univ., College Station, TX (United States); Max-Planck-Institut fuer Quantenoptik (MPQ), Garching (Germany)


    The folklore notion of the &apos;&apos;Non-Locality of Quantum Mechanics&apos;&apos; is examined from the point of view of hidden-variables theories according to Belinfante&apos;s classification in his Survey of Hidden Variables Theories. It is here shown that in the case of EPR, there exist hidden variables theories that successfully reproduce quantum-mechanical predictions, but which are explicitly local. Since such theories do not fall into Belinfante&apos;s classification, we propose an expanded classification which includes similar theories, which we term as theories of the &apos;'third'&apos; kind. Causal implications of such theories are explored. (orig.)

  20. APOE3, but not APOE4, bone marrow transplantation mitigates behavioral and pathological changes in a mouse model of Alzheimer disease. (United States)

    Yang, Yue; Cudaback, Eiron; Jorstad, Nikolas L; Hemingway, Jake F; Hagan, Catherine E; Melief, Erica J; Li, Xianwu; Yoo, Tom; Khademi, Shawn B; Montine, Kathleen S; Montine, Thomas J; Keene, C Dirk


    Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset Alzheimer disease and confers a proinflammatory, neurotoxic phenotype to microglia. Here, we tested the hypothesis that bone marrow cell APOE genotype modulates pathological progression in experimental Alzheimer disease. We performed bone marrow transplants (BMT) from green fluorescent protein-expressing human APOE3/3 or APOE4/4 donor mice into lethally irradiated 5-month-old APPswe/PS1ΔE9 mice. Eight months later, APOE4/4 BMT-recipient APPswe/PS1ΔE9 mice had significantly impaired spatial working memory and increased detergent-soluble and plaque Aβ compared with APOE3/3 BMT-recipient APPswe/PS1ΔE9 mice. BMT-derived microglia engraftment was significantly reduced in APOE4/4 recipients, who also had correspondingly less cerebral apoE. Gene expression analysis in cerebral cortex of APOE3/3 BMT recipients showed reduced expression of tumor necrosis factor-α and macrophage migration inhibitory factor (both neurotoxic cytokines) and elevated immunomodulatory IL-10 expression in APOE3/3 recipients compared with those that received APOE4/4 bone marrow. This was not due to detectable APOE-specific differences in expression of microglial major histocompatibility complex class II, C-C chemokine receptor (CCR) type 1, CCR2, CX3C chemokine receptor 1 (CX3CR1), or C5a anaphylatoxin chemotactic receptor (C5aR). Together, these findings suggest that BMT-derived APOE3-expressing cells are superior to those that express APOE4 in their ability to mitigate the behavioral and neuropathological changes in experimental Alzheimer disease.

  1. Spatial distribution of heavy metals in Hong Kong&apos;s marine sediments and their human impacts: A GIS-based chemometric approach

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Feng [College of Environmental Sciences, Peking University, Beijing 100871 (China)], E-mail:; Guo Huaicheng [College of Environmental Sciences, Peking University, Beijing 100871 (China)], E-mail:; Hao Zejia [College of Environmental Sciences, Peking University, Beijing 100871 (China)


    A geographic information system (GIS)-based chemometric approach was applied to investigate the spatial distribution patterns of heavy metals in marine sediments and to identify spatial human impacts on global and local scales. Twelve metals (Zn, V, Ni, Mn, Pb, Cu, Cd, Ba, Hg, Fe, Cr and Al) were surveyed twice annually at 59 sites in Hong Kong from 1998 to 2004. Cluster analysis classified the entire coastal area into three areas on a global scale, representing different pollution levels. Backward discriminant analysis, with 84.5% correct assignments, identified Zn, Pb, Cu, Cd, V, and Fe as significant variables affecting spatial variation on a local scale. Enrichment factors indicated that Cu, Cr, and Zn were derived from human impacts while Al, Ba, Mn, V and Fe originated from rock weathering. Principal component analysis further subdivided human impacts and their affected areas in each area, explaining 87%, 84% and 87% of the total variances, respectively. The primary anthropogenic sources in the three areas were (i) anti-fouling paint and domestic sewage; (ii) surface runoff, wastewater, vehicle emissions and marine transportation; and (iii) ship repainting, dental clinics, electronic/chemical industries and leaded fuel, respectively. Moreover, GIS-based spatial analysis facilitated chemometric methods.

  2. Identification of human genes involved in cellular responses to ionizing radiation: molecular and cellular studies of gene encoding the p68 helicase in mammalian cells; Identification de genes humains impliques dans la reponse cellulaire aux radiations ionisantes: etudes moleculaire et cellulaire du gene codant l&apos;helicase p68 dans les cellules de mammiferes

    Energy Technology Data Exchange (ETDEWEB)

    Menaa, F.


    Cells submitted to genotoxic factors -like IR- activate several and important mechanisms such as repair, cell cycle arrest or &apos;apoptosis&apos; to maintain genetic integrity. So, the damaged cells will induce many and different genes. The human transcriptome analysis by &apos;SSH&apos; method in a human breast carcinoma cell line MCF7 {gamma}-irradiated versus not irradiated, allowed to identify about one hundred genes. Among of these genes, we have focused our study on a radio-induced gene encoding the p68 helicase. In the conditions of irradiation used, our results show that the kinetic and the regulation of this gene expression differs between the nature of radiations used. Indeed, in {gamma}-irradiated mammalian cells, ATM, a protein kinase activated by DSB and IR, is required to induce quickly P68 gene via the important transcription factor p53 stabilized by IR. In the case of UVC-irradiated cells, the P68 gene induction is late and the intracellular signalling pathway that lead to this induction is independent from the p53 protein. Finally, we show that the p68 protein under-expression is responsible for an increased radiosensitivity of MCF7 cells. Consequently, we can postulate that the p68 protein is involved in cellular responses to radiations to reduce the increased radiosensitivity of cells exposed to {gamma}-rays. (author)

  3. &apos;Bubble-like&apos; lung metastases in osteosarcoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Briccoli, Antonio; Rocca, Michele; Salone, Maria Cristina [General Surgery, Rizzoli Orthopaedic Institute, Bologna (Italy); Di Fiore, Maria [Anaesthesiology, izzoli Orthopaedic Institute, Bologna (Italy); Vanel, Daniel [Research in Imaging, Rizzoli Orthopaedic Institute, Bologna (Italy)], E-mail:; Balladelli, Alba [Laboratory Oncology Research, Rizzoli Orthopaedic Institute, Bologna (Italy); Alberghini, Marco [Pathology, Rizzoli Orthopaedic Institute, Bologna (Italy)


    Purpose: Cavitation of pulmonary metastases have been reported by several authors either as a spontaneous phenomenon or as a consequence of chemotherapy. We present two cases, with this type of image in follow-up, and 20-45 months after the end of treatment. This was the first sign of pulmonary metastases. Results: Two patients with osteogenic sarcoma developed radiological evidence of pulmonary &apos;bubble-like&apos; cavitation several years following completion of chemotherapy. In one patient the &apos;bubble-like&apos; cavitation transformed into a solid nodule. Both patients had surgical resections of all pulmonary lesions, and histology confirmed presence of viable osteosarcoma metastases. Conclusion: The two cases suggest that onset of &apos;bubble-like&apos; cavitation in lung parenchyma of osteosarcoma patients may be the first sign of pulmonary metastases.

  4. The &apos;Instrumental&apos; Reality of Phlogiston

    Directory of Open Access Journals (Sweden)

    Mi Gyung Kim


    Full Text Available The stability of phlogiston in eighteenth-century French chemistry depended not on its role as a comprehensive theory, but on its operational (instrumental, theoretical, and philosophical (speculative identities that were forged in different contexts, yet were interwoven to designate a single substance. It was as &apos;real&apos; as any other chemical substance to the degree that it was obtained through material operations, occupied a place in the theoretical edifice of the affinity table, and was endowed with a corpuscular ontology. Lavoisier labeled it as an &apos;imaginary&apos; substance because it offered a unique resistance to his vision of the new chemistry based on &apos;metric&apos; measurements and algebraic representations.

  5. NDA National Graduate Programme &apos;nucleargraduates&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, Carl


    The aim of this paper is to outline the NDA National Graduate Programme (nuclear graduates). The NDA has a remit under the Energy Act (2004) &apos;to maintain and develop the skills for decommissioning and nuclear clean-up&apos;. Although current research is now being reviewed, there is significant evidence to suggest that the age profile in the Site Licence Companies is skewed towards older workers and there is likely to be a skill shortage in 3-5 years. As nuclear clean-up is a national issue; skill shortages also become a national issue in a very real sense. In addition, evidence suggests that the industry needs to be constantly challenged in order to achieve its targets for decommissioning. The NDA has a unique position under the Act. It is both a strategic overseer and direct employer. To this end the &apos;National Graduate Programme&apos; is aligned to both the NDA&apos;s previous succession plans and the needs of the industry. Industry needs leadership that challenges the status quo and moves the UK nuclear industry to become best in class; Industry needs a dedicated to programme to address skills shortages and difficult to recruit areas such as, but not exclusively, estimators, schedulers, contract managers, site engineers, decommissioning technicians, safety monitors; The NDA has indicated a &apos;commercial and politically savvy&apos; cohort is required to meet its own internal challenges and to ensure sustainability in its own workforce, and to be sensitive to the needs of customers and suppliers alike; Need to create a more diversified workforce in the nuclear industry and also plan for new skills evolving from research and development breakthroughs; Need to ensure that Tier 1, 2, 3 and 4 contractors invest in the leadership and skills for the future. World Class - delivery will be benchmarked against UK based multinational companies who operate in a global graduate attraction and development marketplace. The graduates targeted will be from leading

  6. Why are effective potentials &apos;soft&apos;?

    Energy Technology Data Exchange (ETDEWEB)

    Klapp, Sabine H L; Diestler, Dennis J; Schoen, Martin [Stranski-Laboratorium fuer Physikalische und Theoretische Chemie, Sekretariat TC7, Technische Universitaet Berlin, Strasse des 17 Juni 124, D-10623 Berlin (Germany)


    This paper is concerned with effective potentials W{sub 1}(R) between interacting supramolecular particles separated by a distance R. We focus on the question of why these potentials are typically &apos;soft&apos;, i.e., remain finite for R {yields} 0 and vary more weakly with R than the underlying interatomic interaction potentials. On the basis of a general expression linking W{sub 1}(R) to the free energy F of the supramolecular system we investigate the origin of the apparent &apos;softness&apos; of W{sub 1}(R) by considering a number of special model systems, starting with an atom and a diatomic molecule. This simple model already yields a W{sub 1}(R) that is finite at R = 0, but W{sub 1}(R) does not exhibit the slowly varying character typical of effective potentials for realistic systems. We then show that the larger length scale is recovered when one introduces both many-body interactions and thermal fluctuations within the framework of a &apos;toy model&apos;, that is disc-shaped supramolecular units composed of thermalized configurations of Lennard-Jones atoms. In this case, W{sub 1}(R) varies so slowly that it can be parametrized by estimating the free energy change associated with the overlap of the discs. The resulting overlap approximation to W{sub 1}(R) behaves qualitatively like ad hoc effective potentials used in mesoscale simulations, such as dissipative particle dynamics. Indeed, on the basis of Monte Carlo simulations and a solution of hypernetted chain integral equations, we find that fluids interacting via DPD and overlap potentials have very similar structural and thermophysical properties. Moreover, the &apos;overlap&apos; fluid (like other &apos;effective&apos; fluids) turns out to be so &apos;soft&apos; that its properties, particularly at high densities, can be very well estimated by a mean-field treatment.

  7. Physico-chemical characterization of human recombinant follicle-stimulating hormone (hFSH) and its subunits by reversed-phase high-performance liquid chromatography ( RP-HPLC): comparison with pituitary hFSH reference preparation from &apos;National Hormone and Pituitary Program&apos; from USA; Caracterizacao fisico-quimica da foliculotropina humana(hFSH) recombinabte e de suas subunidades, por cromatografia liquida de alta eficiencia (HPLC) em fase reversa: comparacao com a preparacao de referencia de hFSH de origem hipofisaria do &apos;&apos;National Hormone and Pituitary Program&apos;&apos; dos EUA

    Energy Technology Data Exchange (ETDEWEB)

    Loureiro, Renan Fernandes


    A reversed-phase high-performance liquid chromatography (RP-HPLC) method for the qualitative and quantitative analysis of intact human folliclestimulating hormone (hFSH) was established and validated for accuracy, precision and sensitivity. Human FSH is a dimeric glycoprotein hormone widely used as a diagnostic analyte and as therapeutic product in reproductive medicine. The technique developed preserves the protein integrity, allowing the analysis of the intact heterodimeric form rather than just of its subunits, as it is the case for the majority of the conditions currently employed. This methodology has also been employed for comparing the relative hydrophobicity of pituitary, urinary and two Chinese hamster ovary (CHO)-derived hFSH preparations, as well as of two other related glycoprotein hormones of the anterior pituitary: human thyroid-stimulating hormone (hTSH) and human luteinizing hormone (hLH). The least hydrophobic of the three glycohormones analyzed was hFSH, followed by hTSH and hLH. A significant difference (p<0.005) was observed in t{sub R} between the pituitary and recombinant hFSH preparations, reflecting structural differences in their carbohydrate moieties. Two main isoforms were detected in urinary hFSH, including a form which was significantly different (p<0.005) for the pituitary and recombinant preparations. The linearity of the dose-response curve (r = 0.9965, n = 15) for this RP-HPLC methodology, as well as an inter-assay precision with relative standard deviation less than 4% for the quantification of different hFSH preparations and a sensitivity of the order of 40 ng, were demonstrated. The chromatographic behavior and relative hydrophobicity of the individual subunits of the pituitary and recombinant preparations were also analyzed. Furthermore, the accurate molecular mass of the individual hFSH subunits and of the heterodimer were simultaneously determined by matrix-assisted laser desorption ionization time-of-flight mass spectral

  8. Natural uranium toxicology - evaluation of internal contamination in man; Toxicologie de l&apos;uranium naturel - essai d&apos;evaluation de la contamination interne chez l&apos;homme

    Energy Technology Data Exchange (ETDEWEB)

    Chalabreysse, J. [Commissariat a l' Energie Atomique, Pierrelatte (France). Centre d' Etudes Nucleaires


    After reminding the physical and chemical properties of natural uranium which might affect its toxicology, a comprehensive investigation upon natural uranium metabolism and toxicity and after applying occupational exposure standards to this particular poison, it has been determined, from accident reports and human experience reported in the related literature, a series of formulae obtained by theoretical mathematical development giving principles for internal contamination monitoring and disclosure by determining uranium in the urine of occupationally exposed individuals. An assay is performed to determine individual internal contamination according to the various contamination cases. The outlined purposes, mainly practical, required some options and extrapolations. The proposed formula allows a preliminary approach and also to determine shortly a contamination extent or to discuss the systematical urinalysis results as compared with individual radio-toxicology monitoring professional standards. (author) [French] Apres le rappel des caracteristiques physiques et des proprietes chimiques de l&apos;uranium naturel pouvant avoir une influence sur sa toxicologie, l&apos;etude detaillee de son metabolisme et de sa toxicite, puis l&apos;application des normes professionnelles d&apos;exposition au cas particulier de ce toxique, il est etabli, a partir des comptes rendus d&apos;accidents et de l&apos;experimentation humaine rapportes dans la litterature, une serie de formules obtenues par developpement mathematique theorique qui posent les principes de la surveillance et de la mise en evidence de la contamination interne par la recherche et le dosage de l&apos;uranium dans les urines d&apos;individus professionnellement exposes. Un essai d&apos;evaluation de la contamination interne individuelle suivant les differents cas de contamination est effectue. Le formulaire propose permet de faire une premiere approximation et d&apos;apprecier rapidement l&apos;importance d&apos

  9. On the &apos;efficiency&apos; of futures markets

    Energy Technology Data Exchange (ETDEWEB)

    Bopp, A.E.; Sitzer, Scott


    One definition of market efficiency holds that today&apos;s price of an item contains all the price information that there is about that item. That is, today&apos;s price contains information about peoples&apos; expectations about the future. However, in estimating price equations analysts almost exclusively look to the past in developing price forecasting models. This paper examines the question: how do futures prices affect today&apos;s price for heating oil. That is, do futures markets add to the efficiency of markets by conveying information from the future to the present.

  10. &apos;&apos;Rueckbau 2014&apos;&apos;. KWS Congress regarding decommissioning and dismantling at Zwentendorf nuclear training power plant; &apos;&apos;Rueckbau 2014&apos;&apos;. KWS-Rueckbau-Fachtagung im Schulungskernkraftwerk Zwentendorf

    Energy Technology Data Exchange (ETDEWEB)

    Maassen, Herbert [KRAFTWERKSSCHULE E.V. (KWS), Essen (Germany)


    From September 24 to 25, 2014, KRAFTWERKS-SCHULE E.V. (KWS) held the congress &apos;&apos;Rueckbau 2014&apos;&apos;.This first congress about nuclear power plant decommissioning was combined with an exhibition in the fully equipped Zwentendorf nuclear training power plant. The exhibitors had the opportunity to present and test their products in the ambience of a real nuclear power plant, close to original plant components. The visitors got a general overview of the on-site conditions. During the lectures the process of decommissioning and dismantling of a nuclear power plant were described, problems within this process were discussed, and possible solutions were recommended.

  11. Quantifying the &apos;naturalness&apos; of the curvaton model

    Energy Technology Data Exchange (ETDEWEB)

    Lerner, Rose N. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Helsinki Institute of Physics (Finland); Melville, Scott [Helsinki Institute of Physics (Finland)


    We investigate the probability of obtaining an observable curvature perturbation, using as an example the minimal curvaton-Higgs (MCH) model. We determine &apos;probably observable&apos; and &apos;probably excluded&apos; regions of parameter space assuming generic initial conditions and applying a stochastic approach for the curvaton&apos;s evolution during inflation. Inflation is assumed to last longer than the N{sub obs}≅55 observable e-folds, and the total number of e-folds of inflation determines the particular ranges of parameters that are probable. For the MCH model, these &apos;probably observable&apos; regions always lie within the range 8 x 10{sup 4} GeV≤m{sub σ}≤2 x 10{sup 7} GeV, where m{sub σ} is the curvaton mass, and the Hubble scale at horizon exit is chosen as H{sub *}=10{sup 10} GeV. Because the &apos;probably observable&apos; region depends on the total duration of inflation, information on parameters in the Lagrangian from particle physics and from precision CMB observables can therefore provide information about the total duration of inflation, not just the last N{sub obs} e-folds. This method could also be applied to any model that contains additional scalar fields to determine the probability that these scalar fields contribute to the curvature perturbation.

  12. High-sensitivity gamma spectroscopy for extended sources. Application to activity measurements on the human body, on glass, and on soil; Spectrographie gamma a grande sensibilite pour sources etendues. Application a la mesure de l&apos;activite du corps humain, du verre et du sol

    Energy Technology Data Exchange (ETDEWEB)

    Jouve, B


    The measurement and location by gamma spectroscopy of human body internal contaminations at maximum permissible levels, and, in certain cases, at lower activities such as that due to {sup 40}K was investigated. The characteristics of the high-sensitivity apparatus used are given, and several assemblies using large-volume NaI(Tl) scintillators are described. The relatively light shielding required for natural radioactivity permitted construction of mobile assembly. Conditions of use are described, and the results are given. All gamma emitting elements were measured in 15 min at levels lower than the tolerance dose. Gamma spectroscopy was also used to determine fission products in the earth and to study radioactive elements in the presence of other emitters. (author) [French] La spectrographie gamma du corps humain permet la mesure et la localisation des contaminations internes au niveau des doses de tolerance et, dans certains cas, celle d&apos;activites plus faibles comme la radioactivite naturelle due principalement au potassium 40. Les caracteristiques des appareils a grande sensibilite permettant ces mesures sont exposees et on decrit plusieurs realisations originales utilisant un scintillateur NaI(Tl) de grand volume. L&apos;epaisseur du blindage a ete limitee a 5 cm de plomb, ainsi, pour une protection suffisante contre les rayonnements ambiants, les appareils sont relativement legers et l&apos;une des realisations a pu etre installee dans un laboratoire mobile. Les conditions d&apos;utilisation (mouvement propre, etalonnage) et les resultats obtenus sont donnes; tous les radioelements emetteurs gamma sont mesurables en 15 minutes a un niveau inferieur a la dose de tolerance. On presente enfin des applications a la spectrographie gamma d&apos;echantillons volumineux (poudres ou liquides) et de tres faible activite: elles interessent des domaines tres varies comme, par exemple, la geophysique (etude des retombees radioactives) ou l&apos;industrie chimique

  13. Maintain levels of nicotine but reduce other smoke constituents: a formula for &apos;'less-hazardous'&apos; cigarettes

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, J.C.; Young, J.C.; Rickert, W.S.


    Twenty-two volunteers who smoked more than 20 cigarettes with &apos;'high'&apos; nicotine yields (0.8 to 1.2 mg) per day participated in an 8-week study designed to test the hypothesis that smoking cigarettes with a constant level of nicotine but reduced deliveries of tar, carbon monoxide, and hydrogen cyanide leads to a decrease in smoke absorption. All subjects smoked their usual high-nicotine brand for the first 3 weeks (P1), and the absorption of smoke constituents was determined from levels of thiocyanate and cotinine in saliva and serum, levels of carbon monoxide in expired air, and levels of carboxyhemoglobin in the blood. During the final 5 weeks (P2), the treatment group (16 subjects) switched to the &apos;'light'&apos; version of their usual brands (similar yields of nicotine but with reduced yields of tar, carbon monoxide, and hydrogen cyanide); the control group (6 subjects) smoked their usual brands for the duration of the study. Average levels of cotinine for the subjects who switched during P2 were not significantly different from those of the control group as was expected. Slight reductions were noted in average expired-air carbon monoxide levels, blood carboxyhemoglobin, and saliva thiocyanate, but these reductions were smaller than anticipated based on brand characteristics. The results suggest that the ratio of smoke constituents is different when individuals, rather than machines, smoke cigarettes. Yields determined under subject-defined conditions are necessary in order to properly evaluate the role of nicotine in the design of &apos;'less-hazardous'&apos; cigarettes.

  14. Overview of ozone human exposure and health risk analyses used in the U.S. EPA&apos;s review of the ozone air quality standard.

    Energy Technology Data Exchange (ETDEWEB)

    Whitfield, R. G.


    This paper presents an overview of the ozone human exposure and health risk analyses developed under sponsorship of the U.S. Environmental Protection Agency (EPA). These analyses are being used in the current review of the national ambient air quality standards (NAAQS) for ozone. The analyses consist of three principal steps: (1) estimating short-term ozone exposure for particular populations (exposure model); (2) estimating population response to exposures or concentrations (exposure-response or concentration-response models); and (3) integrating concentrations or exposure with concentration-response or exposure-response models to produce overall risk estimates (risk model). The exposure model, called the probabilistic NAAQS exposure model for ozone (pNEM/03), incorporates the following factors: hourly ambient ozone concentrations; spatial distribution of concentrations; ventilation state of individuals at time of exposure; and movement of people through various microenvironments (e.g., outdoors, indoors, inside a vehicle) of varying air quality. Exposure estimates are represented by probability distributions. Exposure-response relationships have been developed for several respiratory symptom and lung function health effects, based on the results of controlled human exposure studies. These relationships also are probabilistic and reflect uncertainties associated with sample size and variability of response among subjects. The analyses also provide estimates of excess hospital admissions in the New York City area based on results from an epidemiology study. Overall risk results for selected health endpoints and recently analyzed air quality scenarios associated with alternative 8-hour NAAQS and the current 1-hour standard for outdoor children are used to illustrate application of the methodology.

  15. Macrophage-specific apoE gene repair reduces diet-induced hyperlipidemia and atherosclerosis in hypomorphic Apoe mice.

    Directory of Open Access Journals (Sweden)

    Nathalie Gaudreault

    Full Text Available BACKGROUND: Apolipoprotein (apo E is best known for its ability to lower plasma cholesterol and protect against atherosclerosis. Although the liver is the major source of plasma apoE, extra-hepatic sources of apoE, including from macrophages, account for up to 10% of plasma apoE levels. This study examined the contribution of macrophage-derived apoE expression levels in diet-induced hyperlipidemia and atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Hypomorphic apoE (Apoe(h/h mice expressing wildtype mouse apoE at ∼2-5% of physiological levels in all tissues were derived by gene targeting in embryonic stem cells. Cre-mediated gene repair of the Apoe(h/h allele in Apoe(h/hLysM-Cre mice raised apoE expression levels by 26 fold in freshly isolated peritoneal macrophages, restoring it to 37% of levels seen in wildtype mice. Chow-fed Apoe(h/hLysM-Cre and Apoe(h/h mice displayed similar plasma apoE and cholesterol levels (55.53±2.90 mg/dl versus 62.70±2.77 mg/dl, n = 12. When fed a high-cholesterol diet (HCD for 16 weeks, Apoe(h/hLysM-Cre mice displayed a 3-fold increase in plasma apoE and a concomitant 32% decrease in plasma cholesterol when compared to Apoe(h/h mice (602.20±22.30 mg/dl versus 888.80±24.99 mg/dl, n = 7. On HCD, Apoe(h/hLysM-Cre mice showed increased apoE immunoreactivity in lesional macrophages and liver-associated Kupffer cells but not hepatocytes. In addition, Apoe(h/hLysM-Cre mice developed 35% less atherosclerotic lesions in the aortic root than Apoe(h/h mice (167×10(3±16×10(3 µm(2 versus 259×10(3±56×10(3 µm(2, n = 7. This difference in atherosclerosis lesions size was proportional to the observed reduction in plasma cholesterol. CONCLUSIONS/SIGNIFICANCE: Macrophage-derived apoE raises plasma apoE levels in response to diet-induced hyperlipidemia and by such reduces atherosclerosis proportionally to the extent to which it lowers plasma cholesterol levels.

  16. Electrolyzed-water generator &apos;SaniBoy&apos;; Eisei jokinsuik kyokyu sochi &apos;SaniBoy&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, M.; Kakiuchi, H.; Muto, K. [Fuji Electric Co. Ltd., Tokyo (Japan)


    In the food industry, injuries due to food poisoning have been increasing. Especially the mass outbreak of food poisoning by Escherichia coli such as O-157 in 1996 gave warning on the importance of food sanitation management. Public efforts such as the Hazard Analysis and Critical Control Point (HACCP) system have been made to prevent food poisoning. Recently, disinfection made by electrolyzing water with some salt added has attracted attention. Fuji Electric has developed the generator &apos;SaniBoy&apos; that produces weak alkaline electrolyzed water without wasting water. The environment-friendly &apos;SaniBoy&apos; will contribute to sanitation in various fields. (author)

  17. The effect of prior deformation on the foaming behavior of &apos;'FORMGRIP'&apos; precursor material

    Energy Technology Data Exchange (ETDEWEB)

    Frei, J.; Mortensen, A. [Institute of Materials, Ecole Polytechnique Federale de Lausanne, Lausanne, CH-1015 (Switzerland); Gergely, V.; Clyne, T.W. [Department of Materials Science, University of Cambridge, Pembroke Street, Cambridge CB2 3QZ (United Kingdom)


    It is shown that extrusion of &apos;'FORMGRIP'&apos; precursor material prior to baking leads to accelerated foaming and finer, more uniform cell structures. This effect is correlated with microstructural observations made on the precursor materials and on the foams. It is thought that, while extrusion apparently does not extensively fracture the gas-generating hydride particles, it does induce some damage to their protective surface oxide layers. Removal of the porosity normally present in as-cast precursors may also be beneficial. (Abstract Copyright [2002], Wiley Periodicals, Inc.)

  18. Development of an underground system for transporting people at the enterprise &apos;&apos;Bespremskiye ugolnyye shakhty&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Frei, J.; Horvath, M.; Vago, J.


    An examination is made of the stages of development, and advantages are characterized of the mechanized system for transporting people at mines. A technical-economic comparison was made of the possible way to solve the transport problems (variants for the use of cable of winding of the cars, locomotive thrust, belt conveyer transport, freight transport, suspension seats, inclined tracts). Technical characteristics are presented for the thrust devices, cars, loading and unloading stations, and also different equipment used at the Hungarian enterprise &apos;&apos;Bespremskiye ugolnyye shakhty&apos;&apos;.

  19. Dust That&apos;s Worth Keeping

    Energy Technology Data Exchange (ETDEWEB)

    Hazi, A


    ;s Ames Research Center for their discovery. The team analyzed micrometer-size interplanetary dust particles (IDPs), each about one-tenth the diameter of a human hair. Within the particles, they found carriers of the 2,175-angstrom feature: organic carbon mixed with amorphous silicates (glass with embedded metals and sulfides, GEMS), two of the most common materials in interstellar space. Ishii says, &apos;&apos;Organic carbon and amorphous silicates are abundant in interstellar dust clouds, and abundant carriers are needed to account for the frequent astronomical observation of the 2,175-angstrom feature. It makes sense that this ubiquitous feature would come from common materials in interstellar space&apos;&apos;. The group&apos;s results increase scientific understanding of the starting materials for the formation of the Sun, solar system, and life on Earth.

  20. Radiobiological study of the radioprotective activity of a natural Iranian compound, &apos;'Shir-Khecht'&apos;; Etude radiobiologique de l&apos;activite radioprotectrice d&apos;un compose naturel Iranien: le &apos;'Shir-Khecht'&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Rouhanizadeh, N. [Commissariat a l' Energie Atomique, 92 - Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires


    After reviewing the primary mechanisms of the action of ionizing radiation, the possible mechanisms of the action of radioprotective substances, the various chemical structures having a protective effect and the methods for studying chemical radioprotection, the author presents the results he has obtained with natural Iranian product: &apos;'Shir-Khecht'&apos;. Tests with this product at lethal and sublethal doses have been carried out on the rat using various means of introduction. The effect of radiation, both with and without protection, has been studied using histological and biochemical methods. The product examined has, in effect, a protective action; it is, furthermore, non-toxic and active when taken orally. (author) [French] Apres avoir rappele les mecanismes primaires de l&apos;action des rayonnements ionisants, les mecanismes possibles de l&apos;action des substances radioprotectrices, les diverses structures chimiques possedant un effet protecteur et les methodes d&apos;etude de la radioprotection chimique, l&apos;auteur presente les resultats qu&apos;il a obtenus en utilisant un compose naturel iranien: le &apos;'Shir-Khecht'&apos;. Des essais de ce produit, chez le rat, par diverses voies d&apos;introduction, a dose letale et subletale ont ete effectues. L&apos;effet des radiations, avec et sans protection, a ete etudie a l&apos;aide de methodes histologiques et biochimiques. Le compose essaye possede un pouvoir protecteur; il est, de plus, non toxique et actif par voie orale. (auteur)

  1. EAGLE: &apos;EAGLE&apos;Is an&apos; Algorithmic Graph Library for Exploration

    Energy Technology Data Exchange (ETDEWEB)


    The Resource Description Framework (RDF) and SPARQL Protocol and RDF Query Language (SPARQL) were introduced about a decade ago to enable flexible schema-free data interchange on the Semantic Web. Today data scientists use the framework as a scalable graph representation for integrating, querying, exploring and analyzing data sets hosted at different sources. With increasing adoption, the need for graph mining capabilities for the Semantic Web has emerged. Today there is no tools to conduct "graph mining" on RDF standard data sets. We address that need through implementation of popular iterative Graph Mining algorithms (Triangle count, Connected component analysis, degree distribution, diversity degree, PageRank, etc.). We implement these algorithms as SPARQL queries, wrapped within Python scripts and call our software tool as EAGLE. In RDF style, EAGLE stands for "EAGLE &apos;Is an&apos; algorithmic graph library for exploration. EAGLE is like &apos;MATLAB&apos; for &apos;Linked Data.&apos;

  2. The positive impact of &apos;Luz do Campo&apos; program in a rural area: the sericulture in Ribeirao Claro, Parana, Brazil; O impacto positivo do programa &apos;Luz do campo&apos; na extensao rural: a sericicultura em Ribeirao Claro, Parana, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Carmo, Jose R. do; Marques, Rui Manuel B.S.; Betiol Junior, Genesio [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Eletrotecnica e Energia. Programa Interunidades de Pos-Graduacao e Energia], e-mail:, e-mail:, e-mail:; Ribeiro, Fernando Selles [Universidade de Sao Paulo (USP), SP (Brazil). Escola Politecnica de Engenharia], e-mail:


    The &apos;Luz do Campo&apos; program has created positive and favorable impact to the opening of opportunities in the rural area. It has contributed to facilitate the access of workers to energetic facilities and has contributed to providing them with better social and economical conditions. As a consequence after the accomplishment of the rural electrification process in the settlements of &apos;Anhumas&apos; and &apos;Maria Neto&apos; implanted in Ribeirao Claro in Parana, it was possible to come to terms with two projects of Sericiculture in that location. The energy consumption of these projects has not been only restricted to human comfort, but has also been aimed at the production. As a result, the economical success achieved in those settlements in less than a year&apos;s time, is due to the transformation actions in the countryside that have lowered poverty and raised the perspectives of better life quality to the settlers. (author)

  3. Technology &apos;90

    Energy Technology Data Exchange (ETDEWEB)


    The US Department of Energy (DOE) laboratories have a long history of excellence in performing research and development in a number of areas, including the basic sciences, applied-energy technology, and weapons-related technology. Although technology transfer has always been an element of DOE and laboratory activities, it has received increasing emphasis in recent years as US industrial competitiveness has eroded and efforts have increased to better utilize the research and development resources the laboratories provide. This document, Technology &apos;90, is the latest in a series that is intended to communicate some of the many opportunities available for US industry and universities to work with the DOE and its laboratories in the vital activity of improving technology transfer to meet national needs. Technology &apos;90 is divided into three sections: Overview, Technologies, and Laboratories. The Overview section describes the activities and accomplishments of the DOE research and development program offices. The Technologies section provides descriptions of new technologies developed at the DOE laboratories. The Laboratories section presents information on the missions, programs, and facilities of each laboratory, along with a name and telephone number of a technology transfer contact for additional information. Separate papers were prepared for appropriate sections of this report.

  4. Comment on &apos;&apos;Teleportation of two-mode squeezed states&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    He Guangqiang; Zhang Jingtao [State Key Lab of Advanced Optical Communication Systems and Networks Department of Electronic Engineering, Shanghai Jiaotong University, Shanghai 200030 (China)


    We investigate the teleportation scheme of two-mode squeezed states proposed by Adhikari et al.[S. Adhikari et al., Phys. Rev. A 77, 012337 (2008)]. It uses four-mode entangled states to teleport two-mode squeezed states. The fidelity between the original two-mode squeezed states and teleported ones is calculated. The maximal fidelity value of Adhikari&apos;s protocol is 0.38, which is incompatible with the fidelity definition with the maximal value 1. In our opinion, one reason is that they calculate the fidelity for multimodes Gaussian states using the fidelity formula for single-mode ones. Another reason is that the covariance matrix of output states should be what is obtained after applying the linear unitary Bogoliubov operations (two cascaded Fourier transformations) on the covariance matrix given in Eq. (12) in their paper. These two reasons result in the incomparable results. In addition, Adhikari&apos;s protocol can be simplified to be easily implemented.

  5. Nuclear track radiography of &apos;hot&apos; aerosol particles

    Energy Technology Data Exchange (ETDEWEB)

    Boulyga, S.F.; Kievitskaja, A.I.; Kievets, M.K.; Lomonosova, E.M.; Zhuk, I.V.; Yaroshevich, O.I.; Perelygin, V.P.; Petrova, R.; Brandt, R.; Vater, P


    Nuclear track radiography was applied to identify aerosol &apos;hot&apos; particles which contain elements of nuclear fuel and fallout after Chernobyl NPP accident. For the determination of the content of transuranium elements in radioactive aerosols the measurement of the {alpha}-activity of &apos;hot&apos; particles by SSNTD was used in this work, as well as radiography of fission fragments formed as a result of the reactions (n,f) and ({gamma},f) in the irradiation of aerosol filters by thermal neutrons and high energy gamma quanta. The technique allowed the sizes and alpha-activity of &apos;hot&apos; particles to be determined without extracting them from the filter, as well as the determination of the uranium content and its enrichment by {sup 235}U, {sup 239}Pu and {sup 241}Pu isotopes. Sensitivity of determination of alpha activity by fission method is 5x10{sup -6} Bq per particle. The software for the system of image analysis was created. It ensured the identification of track clusters on an optical image of the SSNTD surface obtained through a video camera and the determination of size and activity of &apos;hot&apos; particles00.

  6. Study of diffusion in cartilage by the &apos;'PFG'&apos; (pulsed-field-gradient) NMR technique; Studium der Diffusion im Knorpel mit der &apos;'PFG'&apos; (pulsed-field-gradient)-NMR-Technik

    Energy Technology Data Exchange (ETDEWEB)

    Naji, L.; Trampel, R.; Ngwa, W.; Knauss, R.; Schiller, J.; Arnold, K. [Leipzig Univ. (Germany). Inst. fuer Medizinische Physik und Biophysik


    Since cartilage does not contain any blood vessels, diffusion is the most important mechanism for its supply. Although several methods are available for the measurement of diffusion, this study focuses exclusively on NMR methods. Besides the &apos;'classic'&apos; water diffusion, the diffusion behaviour of ions and polymers in cartilage is also described. In all cases, and at short observation times, diffusion is mostly determined by the water content of the sample. However, the variation of the observation time allows to obtain information also on the internal structure of cartilage. In addition, it is discussed to which extent the individual techniques allow conclusions with respect to degenerative joint diseases, and under which in vivo conditions they can be applied. (orig.) [German] Das Fehlen von Blutgefaessen im Knorpel macht die Diffusion zum wichtigsten Transportmechanismus fuer die Versorgung des Knorpels. Obwohl unterschiedliche Methoden zur Messung von Diffusionsprozessen eingesetzt werden koennen, beschraenken wir uns hie ausschliesslich auf NMR-Methoden. Neben der &apos;'klassischen'&apos; Wasserdiffusion werden auch die Diffusion von Ionen und die Polymerdiffusion in Knorpel beschrieben. In allen Faellen gilt, dass ueber kurze Beobachtungszeiten das Diffusionsverhalten im wesentlichen durch den Wassergehalt bestimmt wird. Jedoch werden durch Variation der Beobachtungszeit auch Informationen ueber die innere Struktur des Knorpels erhalten. Es wird ausserdem dargelegt, inwieweit Techniken Rueckschluesse auf degenerative Gelenkveraenderungen zugelassen und wie sie unter In-vivo-Bedingungen genutzt werden koennten. (orig.)

  7. Development and utilization of a mechanical barrier for large-calibre cavern necks. The &apos;&apos;Spider Plug&apos;&apos;; Entwicklung und Einsatz einer mechanischen Absperrung fuer grosskalibrige Kavernenhaelse. Der &apos;&apos;Spider Plug&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Pfeifer, K.; Maut, D. [UGS GmbH, Mittenwalde (Germany)


    An hydraulic separation of a well and the cavern can be necessary for different workover applications, e.g. casing milling or underreaming. The separation is needed to ensure a mud circulation during such operations. In that case a barrier is set after flooding the cavern, which will then be used as a mechanical abutment for the cement bridge. If the diameter of the cavern neck has been enlarged due to e.g. unwanted leaching processes or unstabilized underreaming processes, it might get impossible to set a standard plug with the available technologies into those diameters. Therefore UGS GmbH has developed a mechanical plug, which is set hydraulically. The so called &apos;Spider Plug&apos; is used as basis for a cement bridge and can be removed by drilling after the workover has been done. Depending on the dimension of the setting tool a cavern neck up to 50&apos;&apos; diameter can be plugged by the &apos;Spider Plug&apos;. Up to now a number of successful operations on different locations has shown, that the &apos;Spider Plug&apos; is a practicable and cost-efficient solution for a mechanical abutment of large cavern necks. (orig.)

  8. Finding the object&apos;&apos; proceedings addendum

    Energy Technology Data Exchange (ETDEWEB)

    Whiting, M.A.; Devaney, D.M.


    The purpose of this workshop was to discuss finding the object -- that is, how software engineers imagine, invent, design, or recycle objects and their behaviors for object-oriented software engineering. The workshop organizers (and, as we subsequently discovered, several of the workshop participants) felt that this issue is crucial to successful object-oriented software engineering (after all, finding objects is what the projects is all about, isn&apos;t it ). Unfortunately, when previous workshops have had the opportunity to review and discuss techniques practitioners use to find objects, too often the results were heated debates on what is an object &apos;&apos; which becomes all consuming. We believed that, given appropriate control over the question of which kind of object&apos;&apos; is being discussed (which meant tell us what object you are trying to find, then tell us your method), a workshop to concentrate on techniques for finding objects would be quite appropriate. 8 refs., 2 figs.

  9. In vivo human apolipoprotein E isoform fractional turnover rates in the CNS.

    Directory of Open Access Journals (Sweden)

    Kristin R Wildsmith

    Full Text Available Apolipoprotein E (ApoE is the strongest genetic risk factor for Alzheimer's disease and has been implicated in the risk for other neurological disorders. The three common ApoE isoforms (ApoE2, E3, and E4 each differ by a single amino acid, with ApoE4 increasing and ApoE2 decreasing the risk of Alzheimer's disease (AD. Both the isoform and amount of ApoE in the brain modulate AD pathology by altering the extent of amyloid beta (Aβ peptide deposition. Therefore, quantifying ApoE isoform production and clearance rates may advance our understanding of the role of ApoE in health and disease. To measure the kinetics of ApoE in the central nervous system (CNS, we applied in vivo stable isotope labeling to quantify the fractional turnover rates of ApoE isoforms in 18 cognitively-normal adults and in ApoE3 and ApoE4 targeted-replacement mice. No isoform-specific differences in CNS ApoE3 and ApoE4 turnover rates were observed when measured in human CSF or mouse brain. However, CNS and peripheral ApoE isoform turnover rates differed substantially, which is consistent with previous reports and suggests that the pathways responsible for ApoE metabolism are different in the CNS and the periphery. We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis.

  10. Narratives as an educational tool : a review of &apos;A Scientific Romance&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, J.; Andrey, J. [Waterloo Univ., ON (Canada). Dept. of Geography


    This paper examined how the use of narratives can be used as a tool for educating the public on climate change with particular reference to Ronald Wright&apos;s 1997 novel entitled A Scientific Romance. The novel develops climate change as a central theme in the development plot and has received excellent reviews from literary critics in Canada, Great Britain and the United States. This paper reviewed the novel using criteria from both cognitive psychology and climatology. Cognitive theory claims that human beings think, perceive, understand and make choices according to narrative structures. This evaluation compared Wright&apos;s depiction of future climate change with scientific projections. Wright provides great detail regarding climatic conditions of the Great London-Thames Estuary region of Southern England in the years 2500-2501. The climatic variables used in the evaluation consist of surface temperature, sea level rise, precipitation and wind speed. This evaluation determined that Wright&apos;s narrative depiction of London&apos;s future climate is much more extreme than what scientists project. It was concluded that Wright&apos;s tightly woven narrative takes an abstract issue and successfully transforms it into something interesting and provides a detailed depiction of a plausible future climate and its implications for society. However, two minor weaknesses were found to exist. First, there is little reference to the major cause of climate change, and secondly, the climate scenario depicted in the novel is more consistent with the runaway greenhouse theory than with scientists&apos; projections. It was cautioned that narratives must be used carefully and responsibly otherwise, the magnitude of portrayed changes may create a sense of disbelief or helplessness on the part of the public. 27 refs., 1 tab.

  11. Changes in epitope exposition of apolipoprotein A-I on the surface of high density lipoproteins after phospholipase A2 treatment. (United States)

    Menschikowski, M; Hempel, U; Dinnebier, G; Lattke, P; Wenzel, K W; Jaross, W


    The immunoreactivity of high density lipoprotein (HDL) modified by treatment with porcine pancreatic phospholipase A2 (PLA2) was studied in a competitive radioimmunoassay using 6 different monoclonal apolipoprotein (apo) A-I antibodies. The competition tests have shown that after PLA2 treatment the immunoreactivity of selected epitopes of apo A-I changed in different ways. While the binding behavior of two epitopes remained unchanged, three epitopes exhibited decreased immunoreactivities after phospholipids hydrolysis. In contrast to the latter epitopes, the immunoreactivity of an epitope located on the cyanogen bromide fragment 4 of apo A-I increased with the degree of lipolysis. A loss of apo A-I from HDL as a consequence of PLA2-treatment did not occur as shown by the determination of the apo A-I concentration in HDL before and after treatment with PLA2. Using overlapped synthetic decapeptides it could be shown that the epitope increasingly exposed on the particle surface of PLA2-modified HDL consists of the amino acid residues 162-173 and 212-229. These residues are characterized by high hydrophobic indices as determined by hydropathy analysis. Furthermore, these regions belong partially to the proposed receptor-binding domain of apo A-I. Thus, an increased exposition of this epitope might result in elevated cellular binding affinities of HDL occurring after modification of lipoproteins by PLA2-treatment.

  12. ApoD mediates binding of HDL to LDL and to growing T24 carcinoma.

    Directory of Open Access Journals (Sweden)

    Sten Braesch-Andersen

    Full Text Available Apolipoprotein (Apo D is an important protein produced in many parts of the body. It is necessary for the development and repair of the brain and protection from oxidative stress. The purpose of this study was to investigate the extent to which apoD interacts with lipoproteins in human plasma. By using detergent-free ELISA, we show that immobilized monoclonal antibodies against apoD very efficiently bind to low density lipoprotein (LDL from plasma; this binding is as equally efficient as binding to an anti-apoB monoclonal antibody. Adding detergent to the plasma inhibited the binding, suggesting that the binding is dependent on the presence of intact lipoprotein particles. Reversing the system by using immobilized anti-apoB revealed that the affinity of apoD for LDL is rather low, suggesting that multiple bindings are needed for a durable connection. Biosensor experiments using purified lipoproteins also showed that purified apoD and high density lipoprotein 3 (HDL3, a lipoprotein fraction rich in apoD, were both able to bind LDL very efficiently, indicating that the HDL3-LDL interaction may be a physiological consequence of the affinity of apoD for LDL. Furthermore, we found that apoD increases the binding of HDL to actively growing T24 bladder carcinoma cells but not to quiescent, contact-inhibited, confluent T24 cells. This result is especially intriguing given that the T24 supernatant only contained detectable levels of apoD after growth inhibition, raising the possibility that alternating the expression of apoD and a putative apoD-receptor could give direction to the flow of lipids. In the current paper, we conclude that apoD mediates binding of HDL to LDL and to growing T24 carcinomas, thereby highlighting the importance of apoD in lipid metabolism.

  13. ApoD mediates binding of HDL to LDL and to growing T24 carcinoma. (United States)

    Braesch-Andersen, Sten; Beckman, Lena; Paulie, Staffan; Kumagai-Braesch, Makiko


    Apolipoprotein (Apo) D is an important protein produced in many parts of the body. It is necessary for the development and repair of the brain and protection from oxidative stress. The purpose of this study was to investigate the extent to which apoD interacts with lipoproteins in human plasma. By using detergent-free ELISA, we show that immobilized monoclonal antibodies against apoD very efficiently bind to low density lipoprotein (LDL) from plasma; this binding is as equally efficient as binding to an anti-apoB monoclonal antibody. Adding detergent to the plasma inhibited the binding, suggesting that the binding is dependent on the presence of intact lipoprotein particles. Reversing the system by using immobilized anti-apoB revealed that the affinity of apoD for LDL is rather low, suggesting that multiple bindings are needed for a durable connection. Biosensor experiments using purified lipoproteins also showed that purified apoD and high density lipoprotein 3 (HDL3), a lipoprotein fraction rich in apoD, were both able to bind LDL very efficiently, indicating that the HDL3-LDL interaction may be a physiological consequence of the affinity of apoD for LDL. Furthermore, we found that apoD increases the binding of HDL to actively growing T24 bladder carcinoma cells but not to quiescent, contact-inhibited, confluent T24 cells. This result is especially intriguing given that the T24 supernatant only contained detectable levels of apoD after growth inhibition, raising the possibility that alternating the expression of apoD and a putative apoD-receptor could give direction to the flow of lipids. In the current paper, we conclude that apoD mediates binding of HDL to LDL and to growing T24 carcinomas, thereby highlighting the importance of apoD in lipid metabolism.

  14. Apolipoprotein E: isoform specific differences in tertiary structure and interaction with amyloid-β in human Alzheimer brain.

    Directory of Open Access Journals (Sweden)

    Phillip B Jones

    Full Text Available We applied a novel application of FLIM-FRET to in situ measurement and quantification of protein interactions to explore isoform specific differences in Aβ-ApoE interaction and ApoE tertiary conformation in senile plaques in human Alzheimer brain. ApoE3 interacts more closely with Aβ than ApoE4, but a greater proportion of Aβ molecules within plaques are decorated with ApoE4 than ApoE3, lending strong support to the hypothesis that isoform specific differences in ApoE are linked with Aβ deposition. We found an increased number of ApoE N-terminal fragments in ApoE4 plaques, consistent with the observation that ApoE4 is more easily cleaved than ApoE3. In addition, we measured a small but significant isoform specific difference in ApoE domain interaction. Based on our in situ data, supported by traditional biochemical data, we propose a pathway by which isoform specific conformational differences increase the level of cleavage at the hinge region of ApoE4, leading to a loss of ApoE function to mediate clearance of Aβ and thereby increase the risk of AD for carriers of the APOEε4 allele.

  15. Deleuze&apos;s Children (United States)

    Hickey-Moody, Anna Catherine


    Children, the image of the child, and the gendered figures of the girl and the boy are thematics that run through the work of Deleuze and feature prominently in his joint writing with Guattari. However, there are many different children in Deleuze&apos;s writings. Various child figures do distinct things in Deleuze&apos;s work. In this article, I…

  16. The energy and monetary implications of the &apos;24/7&apos; &apos;always on&apos; society

    Energy Technology Data Exchange (ETDEWEB)

    Loveday, Dennis L. [Department of Civil and Building Engineering, Loughborough University, Loughborough, Leicestershire LE11 3TU (United Kingdom)], E-mail:; Bhamra, T.; Tang, T. [Department of Design and Technology, Loughborough University, Loughborough, Leicestershire LE11 3TU (United Kingdom); Haines, V.J.A. [Ergonomics and Safety Research Institute (ESRI), Loughborough University, Loughborough, Leicestershire LE11 3TU (United Kingdom); Holmes, M.J. [ARUP, 13, Fitzroy Street, London W1T 4BR (United Kingdom); Green, R.J. [Institute for Energy Research and Policy, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom)


    This paper reviews the trends in society, technology and energy demand of the past 30 years, together with the growth of the &apos;on-demand&apos; culture. The &apos;24/7&apos; or &apos;always on&apos; society can be defined as one where people demand-and generally receive-what they want &apos;now&apos;. It has grown up in parallel with developments in information technology, which have produced the services needed to meet that demand. Larger numbers of appliances, resulting from greater affluence and disposable income, have increased energy use, despite energy efficiencies in other areas. While monetary factors suggest that changes brought about by the 24/7 society will generally be self-correcting at the macro-economic level, there will nevertheless be effects for individuals, such as potentially severe impacts on the fuel poor as electricity prices rise. We conclude with a view of future directions. As the 24/7 culture continues to grow, there is scope for designers and for information technology to manage and reduce energy consumption. This includes buildings, their services systems, and the mix of new technologies that will be deployed over the next 20 years or so, including the possibilities for data exchange and control at the interface between energy suppliers and consumers, coupled with greater understanding of the behaviour of the consumers themselves.

  17. &apos;&apos;Dural tail&apos;&apos; adjacent to acoustic neuroma on MRI: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lunardi, P. (Dept. of Neurological Sciences-Neurosurgery, Univ. ' ' La Sapienza' ' , Rome (Italy)); Mastronardi, L. (Dept. of Neurological Sciences-Neurosurgery, Univ. ' ' La Sapienza' ' , Rome (Italy)); Nardacci, B. (Dept. of Neurological Sciences-Neurosurgery, Univ. ' ' La Sapienza' ' , Rome (Italy)); Acqui, M. (Dept. of Neurological Sciences-Neurosurgery, Univ. ' ' La Sapienza' ' , Rome (Italy)); Fortuna, A. (Dept. of Neurological Sciences-Neurosurgery, Univ. ' ' La Sapienza' ' , Rome (Italy))


    A &apos;dural tail&apos; on Gd-DTPA-enhanced MRI has been often observed adjacent to meningiomas and considered to be useful in distinguishing meningioma of the cerebellopontine angle from acoustic neuroma. However, demonstration of a dural tail adjacent to an acoustic neuroma indicates that this sign is not specific. (orig.)

  18. Possibilities for a sustainable development. Muligheter for en baerekraftig utvikling; Analyser paa &apos;&apos;World Model&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Bjerkholt, O.; Johnsen, T.; Thonstad, K.


    This report is the final report of a project that the Central Bureau of Statistics of Norway has carried out. The report present analyses of the relations between economic development, energy consumption and emission of pollutants to air in a global perspective. The analyses are based on the &apos;&apos;World Model&apos;&apos;, that has been developed at the Institute for Economic Analysis at New York University. The analyses show that it will be very difficult to obtain a global stabilization of the CO[sub 2] emission on the 1990 level. In the reference scenario of the United Nations report &apos;&apos;Our Common Future&apos;&apos;, the increase of CO[sub 2] emissions from 1990 to 2020 was 73%. Even in the scenario with the most drastic measures, the emissions in 2020 will be about 43% above the 1990 level, according to the present report. A stabilization of the global emissions at the 1990 level will require strong measures beyond those assumed in the model calculations, or a considerable breakthrough in energy technology. 17 refs., 5 figs., 21 tabs.

  19. Void effects and the determination of &apos;'patches'&apos; for radiation distribution in heterogeneous multilayer shields

    Energy Technology Data Exchange (ETDEWEB)

    Sayedahmed, F.M.; Makarious, A.S.; Kansouh, W.A. (Atomic Energy Authority, Cairo (Egypt). Reactor and Neutron Physics Dept.)


    The effect on radiation distribution in heterogeneous multilayer shield configurations containing cylindrical air-filled voids of different diameters have been investigated. The heterogeneous shield assemblies were placed in front of one of the horizontal channels of the ET-RR-1 reactor. The measurements of {delta}-rays and slow neutrons were carried out using LiF-7 and LiF-6 Teflon disc dosimeters, respectively. It was found that the presence of air-filled voids increases the radiation along and perpendicular to the void axis. An empirical formula has been derived to calculate the radiation distribution in the multilayer shields and a good agreement between the measured and calculated values was obtained. The formulae developed by Chase have been checked experimentally to determine the minimum amount of &apos;'patching'&apos; required on the outside of the voided shields to maintain a uniform emergent radiation distribution on the outer surface of the shielding assembly. The applicability of this formula has been defined and a semi-empirical formula developed to describe the experimental results obtained for the required &apos;'patching'&apos;. (author).

  20. High-density lipoprotein and apolipoprotein A-I inhibit palmitate-induced translocation of toll-like receptor 4 into lipid rafts and inflammatory cytokines in 3T3-L1 adipocytes. (United States)

    Yamada, Hodaka; Umemoto, Tomio; Kawano, Mikihiko; Kawakami, Masanobu; Kakei, Masafumi; Momomura, Shin-Ichi; Ishikawa, San-E; Hara, Kazuo


    Saturated fatty acids (SFAs) activate toll-like receptor 4 (TLR4) signal transduction in macrophages and are involved in the chronic inflammation accompanying obesity. High-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) produce anti-inflammatory effects via reverse cholesterol transport. However, the underlying mechanisms by which HDL and apoA-I inhibit inflammatory responses in adipocytes remain to be determined. Here we examined whether palmitate increases the translocation of TLR4 into lipid rafts and whether HDL and apoA-I inhibit inflammation in adipocytes. Palmitate exposure (250 μM, 24 h) increased interleukin-6 and tumor necrosis factor-α gene expressions and translocation of TLR4 into lipid rafts in 3T3-L1 adipocytes. Pretreatment with HDL and apoA-I (50 μg/mL, 6 h) suppressed palmitate-induced inflammatory cytokine expression and TLR4 translocation into lipid rafts. Moreover, HDL and apoA-I inhibited palmitate-induced phosphorylation of nuclear factor-kappa B. HDL showed an anti-inflammatory effect via ATP-binding cassette transporter G1 and scavenger receptor class B, member 1, whereas apoA-I showed an effect via ATP-binding cassette transporter A1. These results demonstrated that HDL and apoA-I reduced palmitate-potentiated TLR4 trafficking into lipid rafts and its related inflammation in adipocytes via these specific transporters.

  1. The &apos;&apos;phase velocity&apos;&apos; of nonlinear plasma waves in the laser beat-wave accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Spence, W.L.


    A calculational scheme for beat-wave accelerators is introduced that includes all orders in velocity and in plasma density, and additionally accounts for the influence of plasma nonlinearities on the wave&apos;s phase velocity. The main assumption is that the laser frequencies are very large compared to the plasma frequency - under which it is possible to sum up all orders of forward Raman scattering. It is found that the nonlinear plasma wave does not have simply a single phase velocity, but that the beat-wave which drives it is usefully described by a non-local &apos;&apos;effective phase velocity&apos;&apos; function. A time-space domain approach is followed. (LEW)

  2. Gravity&apos;s rainbow

    Energy Technology Data Exchange (ETDEWEB)

    Magueijo, Joao [Theoretical Physics, Blackett Laboratory, Imperial College, Prince Consort Road, London SW7 2BZ (United Kingdom); Smolin, Lee [Perimeter Institute for Theoretical Physics, Waterloo, N2J 2W9 (Canada)


    Nonlinear special relativity (or doubly special relativity) is a simple framework for encoding properties of flat quantum spacetime. In this paper, we show how this formalism may be generalized to incorporate curvature (leading to what might be called &apos;doubly general relativity&apos;). We first propose a dual to nonlinear realization of relativity in momentum space, and show that for such a dual the spacetime invariant is an energy-dependent metric. This leads to an energy-dependent connection and curvature, and a simple modification to Einstein&apos;s equations. We then examine solutions to these equations. We find the counterpart to the cosmological metric, and show how cosmologies based upon our theory of gravity may solve the &apos;horizon problem&apos;. We discuss the Schwarzschild solution, examining the conditions for which the horizon is energy dependent. Finally, we find the weak field limit.

  3. A novel mutation of the apolipoprotein A-I gene in a family with familial combined hyperlipidemia. (United States)

    Pisciotta, Livia; Fasano, Tommaso; Calabresi, Laura; Bellocchio, Antonella; Fresa, Raffaele; Borrini, Claudia; Calandra, Sebastiano; Bertolini, Stefano


    We report a large family in which four members showed a plasma lipid profile consistent with the clinical diagnosis of familial combined hyperlipidemia (FCHL). One of these patients was found to have markedly reduced HDL cholesterol (HDL-C) (0.72 mmol/l) and Apo A-I (72 mg/dl) levels, a condition suggestive of the presence of a mutation in one of the HDL-related genes. The analysis of APOA1 gene revealed that this patient was heterozygous for a cytosine insertion in exon 3 (c.49-50 ins C), resulting in a frame-shift and premature stop codon at position 26 of pro-Apo A-I (Q17PFsX10). This novel mutation, which prevents the synthesis of Apo A-I, was also found in four family members, including three siblings and the daughter of the proband. Carriers of Apo A-I mutation had significantly lower HDL-C and Apo A-I than non-carriers family members (0.77+/-0.15 mmol/l vs. 1.15+/-0.20 mmol/l, P<0.005; 71.4+/-9.1mg/dl vs. 134.0+/-14.7 mg/dl, P<0.005, respectively). Two of the APOA1 mutation carriers, who were also heavy smokers, had fibrous plaques in the carotid arteries causing mild stenosis (20%). The intimal-media thickness in the two other adult carriers was within the normal range. The other non-carriers family members with FCHL had either overt vascular disease or carotid atherosclerosis at ultrasound examination. This observation suggests that the low HDL-C/low Apo A-I phenotype may result from a genetic defect directly affecting HDL metabolism, even in the context of a dyslipidemia which, like FCHL, is associated with low plasma HDL-C.

  4. Results of the Danish &apos;&apos;high efficiency motors campaign&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Malmose, K.


    In Denmark energy consultancy (demand side management activities (DSM)) took its first steps in the middle of the 80&apos;ies. The energy consultancy was built up around the Danish electric utilities on which the Danish government imposed the implementation of energy savings for funds collected through the electricity bill (approx. 0.0006 DKK/kWh corresponding to approx. 0.001 ECU). The electric utilities trained energy consultants who specialised in visiting industrial enterprises and counselling on energy consumption, primarily focusing on auxiliary systems like lighting, compressed air, ventilation and heating. Within these areas large savings could be obtained because each company was focusing on the actual production but also because the cost of energy was a fraction of the total costs. (orig.)

  5. Crude oil &apos;&apos;Windfall Profit&apos;&apos; Tax Act of 1980

    Energy Technology Data Exchange (ETDEWEB)

    Logan, J.S.


    Administrative problems and compliance planning opportunities are the focus of this overview of the windfall profit tax on crude oil, which is actually an excise tax of a portion of domestic crude oil revenues that is tied to the removal of existing price controls on domestic crude oil. The retroactive effective date of the statute meant that the Internal Revenue Service had to draft and issue interim rules in haste, and now has to mesh the interim and final regulations with the petroleum industry&apos;s regular business practices. Producers, purchasers, and other who are affected by the tax should be alert to potential problems as well as planning opportunities that may develop during this process. The author provides a roadmap through the existing interim regulations to help interpret new changes. 204 references.

  6. EUGRIS: &apos;&apos;European Substainable Land and Groundwater Management Information System&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Frauenstein, J. [Federal Environmental Agency (UBA), Berlin (Germany)


    The presentation outlines and Accompanying Measure with the FP 5 to develop an web based EUropean Sustainable Land and GRoundwater Management Information System information system (EUGRIS). The management of contaminated land and groundwater requires an interdisciplinary approach and a considerable amount of supporting technical information and knowledge. EUGRIS will provide a generally available comprehensive and overarching information and innovation resource, to support both research and practical contaminated land and groundwater management. EUGRI is a gateway to provide a &apos;one stop shop&apos; for information provided by research projects, legislation, standards, best practice and other technical guidance and policy/regulatory publications from the EC, participating Member and Accession States and from various international networks dealing with groundwater and land management issues. Different types of user can access information through different windows according to their needs. EUGRIS will provide its visitors with summary information (digests) and links to sources of more detailed and/or original information in a scaleable holistic and contexturally meaningful way. EUGRIS is being built in three stages: the design of the information system, the development of its software implementation, and the population of the system with information. The presentation is focussed on the concept of the development of the information system with the individual work packages. In the second part of the lecture in particular the work procedures are presented for the content wise replenishment by EUGRIS. The data collation for the proven pilot countries and the production of a European research data base, which opens contents and results of European-wide locked and current projects, form the emphasis thereby. (orig.)

  7. &apos;&apos;Textural analysis of multiparametric MRI detects transition zone prostate cancer&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Sidhu, Harbir S.; Johnston, Edward W.; Taylor, Stuart A.; Halligan, Steve [Centre for Medical Imaging, University College London, London (United Kingdom); University College London Hospitals NHS Foundation Trust, London (United Kingdom); Benigno, Salvatore; Dikaios, Nikos [Centre for Medical Imaging, University College London, London (United Kingdom); Ganeshan, Balaji [Institute of Nuclear Medicine, University College London, University College Hospital, London (United Kingdom); Allen, Clare; Kirkham, Alex [University College London Hospitals NHS Foundation Trust, London (United Kingdom); Groves, Ashley M. [University College London Hospitals NHS Foundation Trust, London (United Kingdom); Institute of Nuclear Medicine, University College London, University College Hospital, London (United Kingdom); Ahmed, Hashim U.; Emberton, Mark [University College London Hospitals NHS Foundation Trust, London (United Kingdom); University College London, Research Department of Urology, London (United Kingdom); Punwani, Shonit [Centre for Medical Imaging, University College London, London (United Kingdom); University College London Hospitals NHS Foundation Trust, London (United Kingdom); Centre for Medical Imaging, University College London and University College London Hospitals NIHR Biomedical Research Centre, London (United Kingdom)


    To evaluate multiparametric-MRI (mpMRI) derived histogram textural-analysis parameters for detection of transition zone (TZ) prostatic tumour. Sixty-seven consecutive men with suspected prostate cancer underwent 1.5T mpMRI prior to template-mapping-biopsy (TPM). Twenty-six men had &apos;significant&apos; TZ tumour. Two radiologists in consensus matched TPM to the single axial slice best depicting tumour, or largest TZ diameter for those with benign histology, to define single-slice whole TZ-regions-of-interest (ROIs). Textural-parameter differences between single-slice whole TZ-ROI containing significant tumour versus benign/insignificant tumour were analysed using Mann Whitney U test. Diagnostic accuracy was assessed by receiver operating characteristic area under curve (ROC-AUC) analysis cross-validated with leave-one-out (LOO) analysis. ADC kurtosis was significantly lower (p < 0.001) in TZ containing significant tumour with ROC-AUC 0.80 (LOO-AUC 0.78); the difference became non-significant following exclusion of significant tumour from single-slice whole TZ-ROI (p = 0.23). T1-entropy was significantly lower (p = 0.004) in TZ containing significant tumour with ROC-AUC 0.70 (LOO-AUC 0.66) and was unaffected by excluding significant tumour from TZ-ROI (p = 0.004). Combining these parameters yielded ROC-AUC 0.86 (LOO-AUC 0.83). Textural features of the whole prostate TZ can discriminate significant prostatic cancer through reduced kurtosis of the ADC-histogram where significant tumour is included in TZ-ROI and reduced T1 entropy independent of tumour inclusion. (orig.)

  8. Genotypizace ApoE u dětí


    Weinfurterová, Radka


    The purpose of this study was to find out how genotype of apolipoprotein E influences blood levels of LDL cholesterol, HDL cholesterol and triglycerides in children. In our study there was found out that apo E genotype has a significant influence on apo E levels, total cholesterol levels and levels of LDL and HDL cholesterol. Subjects with allele apo E4 had significantly higher levels of LDL cholesterol and subjects who carried allele E2 had conversely lower level of LDL cholesterol. These ou...

  9. EAWAG Forum Chriesbach - A &apos;sustainable&apos; new building; EAWAG Forum Chriesbach - Ein &apos;nachhaltiger Neubau&apos; / A &apos;sustainable&apos; new building

    Energy Technology Data Exchange (ETDEWEB)

    Bundi, U. [EAWAG, Duebendorf (Switzerland); Gantenbein, K. [Hochparterre, Zuerich (Switzerland); Preisig, H. [Prof. Hansruedi Preisig, Zuerich (Switzerland); Kasser, U. [Ueli Kasser, Zuerich (Switzerland)


    This monograph describes the &apos;Forum Chriesbach&apos; - a new building for Swiss Federal Institute of Aquatic Science and Technology EAWAG in Duebendorf, Switzerland. The history behind the project and its sustainable concept are discussed. Basic Ideas and an analogy to a typical Swiss farmhouse of earlier centuries are examined. The teamwork that was needed for the building&apos;s realisation is also noted. Architectural topics and the treatment of the building as a total system are discussed. Further topics include water, sanitary installations, material ecology and grey energy. Further, the monograph deals with the realisation of the building, presents key figures and energy balances and comments on the planning and building processes involved.

  10. Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice

    Directory of Open Access Journals (Sweden)

    Zhao Yarui


    Full Text Available Abstract Background Sphingomyelin synthase 2 (SMS2 contributes to de novo sphingomyelin (SM biosynthesis. Its activity is related to SM levels in the plasma and the cell membrane. In this study, we investigated the possibility of a direct relationship between SMS and atherosclerosis. Methods The Adenovirus containing SMS2 gene was given into 10-week ApoE KO C57BL/6J mice by femoral intravenous injection. In the control group, the Adenovirus containing GFP was given. To confirm this model, we took both mRNA level examination (RT-PCR and protein level examination (SMS activity assay. Result We generated recombinant adenovirus vectors containing either human SMS2 cDNA (AdV-SMS2 or GFP cDNA (AdV-GFP. On day six after intravenous infusion of 2 × 1011 particle numbers into ten-week-old apoE KO mice, AdV-SMS2 treatment significantly increased liver SMS2 mRNA levels and SMS activity (by 2.7-fold, 2.3-fold, p Conclusions Our results present direct morphological evidence for the pro-atherogenic capabilities of SMS2. SMS2 could be a potential target for treating atherosclerosis.

  11. Regulation of heating and air-conditioning systems based on human thermal sensation: impact on the energy consumption in buildings; Regulation des systemes de chauffage et de climatisation basee sur la sensation thermique humaine: impact sur la consommation d&apos;energie dans les batiments

    Energy Technology Data Exchange (ETDEWEB)

    Endravadan, M.


    This study is based on the adaptive approach. The thermal comfort of an individual depends on indoor conditions that can be controlled. However, changes in activity or clothing adjustments are difficult to control and measure in the field experiments. Behavioural actions undertaken by the occupant to overcome the discomfort could be varying and may have diverse consequences. Sometimes these actions are beneficial to the occupant, although often they lead to disastrous amounts of energy consumption. Hence, it becomes crucial to consider the human behaviour and the thermal inertia of the building. The creation of numerical models is useful to study the coupling between these two components and to evaluate the effects of the behaviour on comfort and the energy. The simulations were conducted using TRNSYS software. A model such as &apos;Global Behavioural Regulator&apos; (GBR) was created to evaluate the effects of clothing or thermostat adjustments made by the occupant depending on his thermal sensation (PMV). The energy costs of several types of regulators have been compared in various seasons for example, winter and summer using a light and heavy weight building. The heating of a whole-building may not be necessary in temperate climates or during mid-season. However, comfortable working conditions could be assured for the occupants with the use of an individual heating system such as a &apos;Local Heating System&apos; (LHS). In such a context, it becomes interesting to evaluate the occupant&apos;s behaviour in regards to local heating and its effects on comfort and energy consumption. The LHS consists of three radiant panels; therefore, it is important to evaluate the local heat exchanges with precision. Experiments conducted with the manikin were used to validate the infra-red model; whereas experiments with real subjects were studied to understand the occupant behaviour on the LHS as a function of their local thermal sensations. These analyses led to the creation

  12. Documentation to the workshop &apos;Cluster in the environmental protection economy&apos;; Dokumentation zum Workshop &apos;&apos;Cluster in der Umweltschutzwirtschaft&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)



    Within the workshop &apos;Cluster in the environmental protection economy&apos; at the Umweltbundesamt (Dessau-Rosslau, Federal Republic of Germany) at 27th November, 2008, the following lectures were held: (a) Which contribution can cluster and cluster politics contribute to the promotion of the environmental protection economy? (Harald Legler); (b) Cluster in the environmental protection economy: Targets and expectations (Dieter Rehfeld); (c) Demands at the management of clusters (Karin Hoerhan); (d) Demands at the cluster politics in the environmental protection economy (Bernhard Hausberg); (e) Photovoltaics in Eastern Germany (Johann Wackenbauer); (f) Automotive industry in Bergisches Land (Thomas Lemken); (g) Competence centre environment Augsburg-Schwaben (Egon Beckord).

  13. Apolipoprotein A-I Modulates Processes Associated with Diet-Induced Nonalcoholic Fatty Liver Disease in Mice (United States)

    Karavia, Eleni A; Papachristou, Dionysios J; Liopeta, Kassiani; Triantaphyllidou, Irene-Eva; Dimitrakopoulos, Odyssefs; Kypreos, Kyriakos E


    Apolipoprotein A-I (apoA-I) is the main protein of high-density lipoprotein (HDL). We investigated the involvement of apoA-I in diet-induced accumulation of triglycerides in hepatocytes and its potential role in the treatment of nonalcoholic fatty liver disease (NAFLD). ApoA-I–deficient (apoA-I−/−) mice showed increased diet-induced hepatic triglyceride deposition and disturbed hepatic histology while they exhibited reduced glucose tolerance and insulin sensitivity. Quantification of FASN (fatty acid synthase 1), DGAT-1 (diacylglycerol O-acyltransferase 1), and PPARγ (peroxisome proliferator-activated receptor γ) mRNA expression suggested that the increased hepatic triglyceride content of the apoA-I−/− mice was not due to de novo synthesis of triglycerides. Similarly, metabolic profiling did not reveal differences in the energy expenditure between the two mouse groups. However, apoA-I−/− mice exhibited enhanced intestinal absorption of dietary triglycerides (3.6 ± 0.5 mg/dL/min for apoA-I−/− versus 2.0 ± 0.7 mg/dL/min for C57BL/6 mice, P triglycerides and a reduced rate of hepatic very low density lipoprotein (VLDL) triglyceride secretion (9.8 ± 1.1 mg/dL/min for apoA-I−/− versus 12.5 ± 1.3 mg/dL/min for C57BL/6 mice, P triglyceride content and an improvement of hepatic histology and architecture. Our data extend the current knowledge on the functions of apoA-I, indicating that in addition to its well-established properties in atheroprotection, it is also an important modulator of processes associated with diet-induced hepatic lipid deposition and NAFLD development in mice. Our findings raise the interesting possibility that expression of therapeutic forms of apoA-I by gene therapy approaches may have a beneficial effect on NAFLD. PMID:22576368

  14. Estimation of doses to patients from &apos;'complex'&apos; conventional X-ray examinations

    Energy Technology Data Exchange (ETDEWEB)

    Calzado, A.; Vano, E.; Moran, P.; Ruiz, S.; Gonzalez, L. (Universidad Complutense de Madrid (Spain). Catedra de Fisica Medica); Castellote, C. (Hospital Militar Central ' ' Gomez Ulla' ' , Madrid (Spain). Dept. de Radiologia)


    A numerical method has been developed to estimate organ doses and effective dose-equivalent for patients undergoing three &apos;complex&apos; examinations (barium meal, barium enema and intravenous urography). The separation of radiological procedures into a set of standard numerical views is based on the use of Monte Carlo conversion factors and measurements within a Remab phantom. Radiation doses measured in a phantom for such examinations were compared with predictions of the &apos;'numerical'&apos; method. Dosimetric measurements with thermoluminescent dosemeters attached to the patient&apos;s skin along with measurements of the dose-area product during the examination have enabled the derivation of organ doses and to estimate effective dose-equivalent. Mean frequency weighted values of dose-area product, energy imparted to the patient, doses to a set of organs and effective dose-equivalent in the area of Madrid are reported. Comparisons of results with those from similar surveys in other countries were made. (author).

  15. Apolipoprotein-E forms dimers in human frontal cortex and hippocampus

    Directory of Open Access Journals (Sweden)

    Halliday Glenda M


    Full Text Available Abstract Background Apolipoprotein-E (apoE plays important roles in neurobiology and the apoE4 isoform increases risk for Alzheimer's disease (AD. ApoE3 and apoE2 are known to form disulphide-linked dimers in plasma and cerebrospinal fluid whereas apoE4 cannot form these dimers as it lacks a cysteine residue. Previous in vitro research indicates dimerisation of apoE3 has a significant impact on its functions related to cholesterol homeostasis and amyloid-beta peptide degradation. The possible occurrence of apoE dimers in cortical tissues has not been examined and was therefore assessed. Human frontal cortex and hippocampus from control and AD post-mortem samples were homogenised and analysed for apoE by western blotting under both reducing and non-reducing conditions. Results In apoE3 homozygous samples, ~12% of apoE was present as a homodimer and ~2% was detected as a 43 kDa heterodimer. The level of dimerisation was not significantly different when control and AD samples were compared. As expected, these dimerised forms of apoE were not detected in apoE4 homozygous samples but were detected in apoE3/4 heterozygotes at a level approximately 60% lower than seen in the apoE3 homozygous samples. Similar apoE3 dimers were also detected in lysates of SK-N-SH neuroblastoma cells and in freshly prepared rabbit brain homogenates. The addition of the thiol trapping agent, iodoacetamide, to block reactive thiols during both human and rabbit brain sample homogenisation and processing did not reduce the amount of apoE homodimer recovered. These data indicate that the apoE dimers we detected in the human brain are not likely to be post-mortem artefacts. Conclusion The identification of disulphide-linked apoE dimers in human cortical and hippocampal tissues represents a distinct structural difference between the apoE3 and apoE4 isoforms that may have functional consequences.

  16. Effect of Apolipoprotein A-I on ATP Binding Cassette Transporter A1 Degradation and Cholesterol Efflux in THP-1 Macrophage-derived Foam Cells

    Institute of Scientific and Technical Information of China (English)

    Chao-Ke TANG; Chang-Geng RUAN; Yong-Zong YANG; Guo-Hua TANG; Guang-Hui IY; Zuo WANG; Lu-Shan LIU; Shuang WAN; Zhong-Hua YUAN; Xiu-Sheng HE; Jun-Hao YANG


    Cholesterol-loaded macrophage foam cells are a central componentof atherosclerotic lesions ATP binding cassette transporter A1(ABCA1),the defective molecule in Tangier disease,mediates the efflux ofphospholipid and cholesterol from cells to apolipoprotein A-I(apoA-I),reversing foam cell formation.This study investigated the effect of apoA-I on ABCA1 degradation and cholesterol efflux in THP-1 macrophagederived foam cells.After exposure of the cultured THP-1 macrophage-derived foam cells to apoA-I for different time,cholesterol efflux,ABCA1 mRNA and protein levels were determined by FJ-2107P type liquid scintillator,RT-PCR and Western blot,respectively.The mean ABCA1 fluorescence intensity on THP-1macrophage-derived foam cells was detected by flow cytometry.Results showed that apoA-I markedly increased ABCAl-mediated cholesterol efflux from THP-1 macrophage-derived foam cells.This was accompanied by an increase in the content of ABCA1.ApoA-I did not alter ABCA 1 mRNA abundance.Significantly,thiol protease inhibitors increased the level ofABCA1 protein and slowed its decay in THP-1macrophage-derived foam cells,whereas none of the proteosome-specific inhibitor lactacystin,other protease inhibitors,or the lysosomal inhibitor NH4Cl showed such effects.The apoA-I-mediated cellular cholesterol efflux was enhanced by thiol protease inhibitors.Our results suggested that thiol protease inhibitors mightprovide an alternative way to upregulate ABCA1 protein.This strategy is especially appealing since it may mimic the stabilizing effect of the natural ligands apoA-I.

  17. ApoC-III: a potent modulator of hypertriglyceridemia and cardiovascular disease (United States)

    Kohan, Alison B.


    Purpose of review To summarize the recent epidemiological, basic science, and pharmaceutical research linking apoC-III with the development and treatment of cardiovascular disease. Recent findings ApoC-III is an important emerging target linking hypertriglyceridemia with cardiovascular disease (CVD). ApoC-III is a potent modulator of many established CVD risk factors, and is found on chylomicrons, VLDL, LDL, and HDL particles. Recent studies show that in humans, apoC-III levels are an independent risk factor for CVD, and its presence on lipoproteins may promote their atherogenicity. This year, two large-scale epidemiological studies have linked mutations in apoC-III with increased incidence of cardiovascular disease and hypertriglyceridemia. ApoC-III raises plasma triglycerides through inhibition of LPL, stimulation of VLDL secretion, and is a novel factor in modulating intestinal triglyceride trafficking. ApoC-III also stimulates inflammatory processes in the vasculature and in the pancreas. The combination of raising plasma triglycerides and independently stimulating inflammatory processes makes apoC-III a valuable target for reducing the residual CVD risk in patients already on statin therapy, or for whom triglycerides are poorly controlled. Clinical trials on apoC-III antisense oligonucleotides are in progress. Summary ApoC-III is a potent direct modulator of established cardiovascular disease risk factors: plasma triglycerides and inflammation. Recent findings show that changes in apoC-III levels are directly associated with changes in cardiovascular risk, and with the atherogenicity of the lipoproteins on which apoC-III resides. Emerging roles of apoC-III include a role in directing the atherogenicity of HDL, intestinal dietary triglyceride trafficking, and modulating pancreatic β-cell survival. The combination of these roles makes apoC-III an important therapeutic target for the management and prevention of cardiovascular disease. PMID:25692924

  18. &apos;Catapult&apos; offshore renewables into commercial use

    Energy Technology Data Exchange (ETDEWEB)

    Block, Elizabeth


    In February, the Technology Strategy Board, the UK&apos;s government innovation agency, appointed a consortium to set up the Offshore Renewable Energy Catapult centre, with Sterling Pounds 50 million to be spent over five years. (orig.)

  19. &apos;&apos;Rueckbau 2014&apos;&apos;. KWS congress regarding decommissioning and dismantling at nuclear training power plant Zwentendorf; &apos;&apos;Rueckbau 2014&apos;&apos;. KWS-Rueckbau-Fachtagung im Schulungskernkraftwerk Zwentendorf

    Energy Technology Data Exchange (ETDEWEB)

    Maassen, Herbert [KRAFTWERKSSCHULE e.V. (KWS), Essen (Germany)


    From September 24th to 25th, 2014 the KRAFTWERKSSCHULE E.V. (KWS) held the congress &apos;&apos;Rueckbau 2014&apos;&apos;. This first congress about the deconstruction of nuclear power plants was combined with an exhibition in the fully equipped nuclear training power plant Zwentendorf. The exhibitors had the opportunity to present and test their products in the ambience of a real nuclear power plant, close to original plant components. The visitors got a general overview of the on-site conditions. During the lectures the process of decommissioning and dismantling of a nuclear power plant was described, problems within this process were discussed, and possible solutions were recommended. The congress influenced significantly the dialogue of all parties involved and contributed to an extensive exchange of knowledge and experience.

  20. Container design testing for the final repository Konrad - experiences with respect to so called &apos;'old'&apos; containers; Bauartpruefungen an Behaeltern fuer das Endlager KONRAD. Erfahrungen bezueglich sog. &apos;'Alt'&apos;-Behaelter

    Energy Technology Data Exchange (ETDEWEB)

    Noack, Volker; Voelzke, Holger; Nieslony, Gregor; Kovacs, Oliver; Hagenow, Peter [BAM Bundesanstalt fuer Materialforschung und -pruefung (Germany)


    The Konrad ore mine is a final repository for low- and intermediate-level radioactive waste in Germany. The demand for final storage suitable containers is increasing. The authors describe tests of so called &apos;'old'&apos; containers for qualification with respect to the appropriateness for final disposal. BAM (Bundesanstalt fuer Materialpruefung) has test facilities for drop tests and fire tests. The testing requirements for all available container types are discussed, including the boundary conditions with respect to the supposed waste properties, conditioning and loading. The project of container design testing is aimed to the possibility of a continuous recording of a large amount of waste packages for the final repository Konrad that allows a short-term backtracking of the relevant data for quality assurance.

  1. &apos;&apos;Life-cycle costs&apos;&apos; of industrial electric drives in the process industry - energy consumption and economics of electric drives

    Energy Technology Data Exchange (ETDEWEB)

    Bieniek, K. [BASF AG, Ludwigshafen (Germany)


    For electric motors in the process industry, the purchase price is only a small fraction of the overall &apos;&apos;life-cycle costs&apos;&apos;. The most important criteria are reliability, noise and efficiency. The engineering expense for assessing energy consumption must be kept in accordance to the saving potential. In the German chemical industry, reliability has attained an encouragingly high level thanks to applying the &apos;&apos;VIK recommendations&apos;&apos;. Standardised sizes (&apos;&apos;European standard motor&apos;&apos;) guarantee the interchangeability. That gives also a good basis for introducing improved motors, e.g. with less noise or with better efficiency. Today&apos;s market offers already a high level of efficiencies: Improvements will justify only small price increases. Despite their large number, small motors of less than 1 kW consume only a small percentage of the total electricity demand in a plant, and for large motors (above 100 kW) energy losses are already evaluated in detail. For the &apos;&apos;standard motors&apos;&apos; approximately between 1 and 100 kW, a standardised classification and labelling of the motor efficiencies will be a useful tool for selecting the optimal motors for their applications. To ensure interchangeability, the motor sizes and installation dimensions must remain unchanged. (orig.)

  2. Swiss &apos;Electricity&apos; Research Programme 2004-2007; Konzept des Forschungsprogramms &apos;Elektrizitaet&apos; 2004 - 2007

    Energy Technology Data Exchange (ETDEWEB)

    Brueniger, R.


    This report issued by the Swiss Federal Office of Energy (SFOE) provides details on Swiss research in the electricity area that is foreseen for the period 2004-2007. The report discusses the current state of electricity research and the strategic goals for the period and presents the organisations involved and their previous work. The general main areas of interest addressed by the programme are noted, such as the storage and transport of electricity as well as its use in communication technologies, motors, domestic appliances and industrial applications. Figures are presented on the programme&apos;s finances and the concept of &apos;trend-watching&apos; groups is briefly addressed.

  3. Fluorescence study of domain structure and lipid interaction of human apolipoproteins E3 and E4. (United States)

    Mizuguchi, Chiharu; Hata, Mami; Dhanasekaran, Padmaja; Nickel, Margaret; Okuhira, Keiichiro; Phillips, Michael C; Lund-Katz, Sissel; Saito, Hiroyuki


    Human apolipoprotein E (apoE) isoforms exhibit different conformational stabilities and lipid-binding properties that give rise to altered cholesterol metabolism among the isoforms. Using Trp-substituted mutations and site- directed fluorescence labeling, we made a comprehensive comparison of the conformational organization of the N- and C-terminal domains and lipid interactions between the apoE3 and apoE4 isoforms. Trp fluorescence measurements for selectively Trp-substituted variants of apoE isoforms demonstrated that apoE4 adopts less stable conformations in both the N- and C-terminal domains compared to apoE3. Consistent with this, the conformational reorganization of the N-terminal helix bundle occurs at lower guanidine hydrochloride concentration in apoE4 than in apoE3 as monitored by fluorescence resonance energy transfer (FRET) from Trp residues to acrylodan attached at the N-terminal helix. Upon binding of apoE3 and apoE4 variants to egg phosphatidylcholine small unilamellar vesicles, similar changes in Trp fluorescence or FRET efficiency were observed for the isoforms, indi- cating that the opening of the N-terminal helix bundle occurs similarly in apoE3 and apoE4. Introduction of mutations into the C-terminal domain of the apoE isoforms to prevent self-association and maintain the monomeric state resulted in great increase in the rate of binding of the C-terminal helices to a lipid surface. Overall, our results demonstrate that the different conformational organizations of the N- and C-terminal domains have a minor effect on the steady-state lipid-binding behavior of apoE3 and apoE4: rather, self-association property is a critical determinant in the kinetics of lipid binding through the C-terminal helices of apoE isoforms.

  4. A &apos;missing&apos; family of classical orthogonal polynomials

    Energy Technology Data Exchange (ETDEWEB)

    Vinet, Luc [Centre de Recherches Mathematiques, Universite de Montreal, PO Box 6128, Centre-ville Station, Montreal, Quebec, H3C 3J7 (Canada); Zhedanov, Alexei, E-mail: [Donetsk Institute for Physics and Technology, Donetsk 83114 (Ukraine)


    We study a family of &apos;classical&apos; orthogonal polynomials which satisfy (apart from a three-term recurrence relation) an eigenvalue problem with a differential operator of Dunkl type. These polynomials can be obtained from the little q-Jacobi polynomials in the limit q = -1. We also show that these polynomials provide a nontrivial realization of the Askey-Wilson algebra for q = -1.

  5. What does &apos;'Platinum'&apos; mean? Reflections on the development of sustainability assessment methods; Was bedeutet &apos;'Platin'&apos;? - Zur Entwicklung von Nachhaltigkeitsbewertungsverfahren

    Energy Technology Data Exchange (ETDEWEB)

    Gertis, Karl [Lehrstuhl fuer Bauphysik, Universitaet Stuttgart (Germany); Hauser, Gerd [echnischen Universitaet Muenchen (Germany); Sedlbauer, Klaus [Universitaet Stuttgart (DE). Fraunhofer-Institut fuer Bauphysik (IBP); Sobek, Werner [Universitaet Stuttgart (DE). Institut fuer Leichtbau Entwerfen und Konstruieren (ILEK)


    The current political discussion on climate change is heavily biased towards CO{sub 2} balance, energy consumption and energy costs associated with rising energy prices. The good news is that the German Government covers sustainability in the construction sector, including - and indeed going far beyond - energy conservation. To this end the German Sustainable Building Council (DGNB) was formed in 2007, although it is worth noting that Great Britain introduced a relatively advanced sustainability assessment method referred to as BREEAM as early as 1990, an enhanced version of which was released in the USA in 1995 under the name of LEED. This article tries to show &apos;'rootstocks'&apos; for the sustainability assessment, to set up a classification system for criteria, and to derive consequences. (Abstract Copyright [2008], Wiley Periodicals, Inc.) [German] In der derzeitigen politischen Diskussion ueber die Klimaveraenderung wird der CO{sub 2}-Bilanz und dem Energieverbrauch bzw. den mit steigenden Energiepreisen verbundenen Energiekosten eine fast ueberlastige Bedeutung beigemessen. Umso erfreulicher ist es, dass sich die Bundesregierung mit einem Leitfaden auch der Nachhaltigkeit des Bauens annimmt, welche die Energieeinsparung einschliesst, aber weit ueber diese hinausgeht, und dass sich hierzu im Jahre 2007 - wenn auch im internationalen Vergleich spaet - die Deutsche Gesellschaft fuer nachhaltiges Bauen (DGNB) gebildet hat; verspaetet deshalb, weil in Grossbritannien mit BREEAM bereits 1990 ein relativ ausgereiftes Nachhaltigkeitsbewertungsverfahren bekannt geworden war, auf das in den USA mit LEED 1995 aufgebaut wurde. Die vorliegende Arbeit versucht, &apos;'Grundstoecke'&apos; fuer die Nachhaltigkeitsbeurteilung aufzuzeigen, ein Kriterien-Ordnungssystem aufzubauen und daraus einige Konsequenzen abzuleiten. (Abstract Copyright [2008], Wiley Periodicals, Inc.)

  6. SAP deficiency mitigated atherosclerotic lesions in ApoE(-/-) mice. (United States)

    Zheng, Lingyun; Wu, Teng; Zeng, Cuiling; Li, Xiangli; Li, Xiaoqiang; Wen, Dingwen; Ji, Tianxing; Lan, Tian; Xing, Liying; Li, Jiangchao; He, Xiaodong; Wang, Lijing


    Serum amyloid P conpoent (SAP), a member of the pentraxin family, interact with pathogens and cell debris to promote their removal by macrophages and neutrophils and is co-localized with atherosclerotic plaques in patients. However, the exact mechanism of SAP in atherogenesis is still unclear. We investigated whether SAP influence macrophage recruitment and foam cell formation and ultimately affect atherosclerotic progression. we generated apoE(-/-); SAP(-/-) (DKO) mice and fed them western diet for 4 and 8 weeks to characterize atherosclerosis development. SAP deficiency effectively reduced plaque size both in the aorta (p = 0.0006 for 4 wks; p = 0.0001 for 8 wks) and the aortic root (p = 0.0061 for 4 wks; p = 0.0079 for 8wks) compared with apoE(-/-) mice. Meanwhile, SAP deficiency inhibited oxLDL-induced foam cell formation (p = 0.0004) compared with apoE(-/-) mice and SAP treatment increases oxLDL-induced foam cell formation (p = 0.002) in RAW cells. Besides, SAP deficiency reduced macrophages recruitment (p = 0.035) in vivo and in vitro (p = 0.026). Furthermore, SAP treatment enhanced CD36 (p = 0.007) and FcγRI (p = 0.031) expression induced by oxLDL through upregulating JNK and p38 MAPK phosphorylation whereas specific JNK1/2 inhibitor reduced CD36 (p = 0.0005) and FcγRI (P = 0.0007) expression in RAW cell. SAP deficiency also significantly decreased the expression of M1 and M2 macrophage markers and inflammatory cytokines in oxLDL-induced macrophages. SAP deficiency mitigated foam cell formation and atherosclerotic development in apoE(-/-) mice, due to reduction in macrophages recruitment, polarization and pro-inflammatory cytokines and inhibition the CD36/FcγR-dependent signaling pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. An engineering geology approach applied to objective risk analysis&apos;&apos; and for the quantification of the probability of success&apos;&apos; of petroleum leads&apos;&apos; and prospects&apos;&apos;

    Energy Technology Data Exchange (ETDEWEB)

    Font, R.G. (Geoscience Data Management, Dallas, TX (United States))


    In engineering geology, people often labor to standardize and quantify techniques and methods utilized in the solution of critical problems. Applications related to the field of petroleum technology are certainly no exception. For example, risk analysis of petroleum exploratory projects and prospects is often arbitrary and biased. The calculation of prospect risk introduced in this article is designed to remove subjectivity&apos;&apos; by establishing quantitative standards.&apos;&apos; The technique allows the same method of analysis to be applied to prospects worldwide. It may be used as introduced in this paper (as employed by the author) or as a model, since it possesses the flexibility to be modified by individual users as long as standards are internally defined and utilized by all members of an exploration team. Risk analysis has been discussed in much detail. However, an original method for establishing quantitative standards for risk assessment is addressed and introduced in this paper. As defined here, prospect risk (described as the probability of success&apos;&apos; or Ps&apos;&apos;) is the product of the following: Ps = (Trap) [times] (Reservoir) [times] (Source) [times] (Recovery) [times] (Timing). Well-defined, quantitative standards must be established if one is to remove subjectivity from risk assessment. In order to establish such standards to be used uniformly by explorationists, each of the above-referenced factors is individually evaluated and numerically defined utilizing the category and ranking system outlined in Table 1. If all five, independent parameters had individual values of 1.00, then the prospective venture would have an overall probability of success of 100 percent. Similarly, if all parameters exhibited values of 0.90, the overall chance of success would equal 77 percent. Values of 0.80 equate to 33 percent, values of 0.70 to 17 percent, values of 0.60 to 8 percent, values of 0.50 to 1 percent, and values of 0.30 to 0.2 percent.

  8. The &apos;Instrumental&apos; Reality of Phlogiston


    Mi Gyung Kim


    The stability of phlogiston in eighteenth-century French chemistry depended not on its role as a comprehensive theory, but on its operational (instrumental), theoretical, and philosophical (speculative) identities that were forged in different contexts, yet were interwoven to designate a single substance. It was as &apos;real&apos; as any other chemical substance to the degree that it was obtained through material operations, occupied a place in the theoretical edifice of the affinity table, ...

  9. The First Synthesis and Anti-retroviral Activity of 5&apos;,5&apos;-Difluoro-3&apos;-Hydroxy-Apiosyl Nucleoside Cyclomonophosphonic Acid Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seyeon; Hong, Joon Hee [Chosun University, Gwangju (Korea, Republic of)


    The first synthesis of novel 5&apos;,5&apos;-difluoro-30-hydroxy apiose nucleoside cyclomonophosphonic acid analogs was performed as potent anti-retroviral agents. Phosphonation was performed by direct displacement of a triflate intermediate with diethyl(lithiodifluoromethyl) phosphonate to give the corresponding(α, α-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield the nucleoside phosphonate analogs. Deprotection of diethyl phosphonates provided the target nucleoside cyclomonophosphonic acid analogs. The synthesized nucleoside analogs were subjected to anti-viral screening against the human immunodeficiency virus-1 (HIV-1). Cytosine analogs show significant anti-HIV activity.

  10. ApoE4 induces synaptic and ERG impairments in the retina of young targeted replacement apoE4 mice.

    Directory of Open Access Journals (Sweden)

    Ran Antes

    Full Text Available The vertebrate retina, which is part of the central nervous system, is a window into the brain. The present study investigated the extent to which the retina can be used as a model for studying the pathological effects of apolipoprotein E4 (apoE4, the most prevalent genetic risk factor for Alzheimer's disease (AD. Immunohistochemical studies of retinas from young (4 months old apoE4-targeted replacement mice and from corresponding mice which express the AD benign apoE3 allele, revealed that the density of the perikarya of the different classes of retinal neurons was not affected by apoE4. In contrast, the synaptic density of the retinal synaptic layers, which was assessed immunohistochemically and by immunoblot experiments, was significantly lower in the apoE4 than in the apoE3 mice. This was associated with reduced levels of the presynaptic vesicular glutamatergic transporter, VGluT1, but not of either the GABAergic vesicular transporter, VGaT, or the cholinergic vesicular transporter, VAChT, suggesting that the glutamatergic nerve terminals are preferentially affected by apoE4. In contrast, the post synaptic scaffold proteins PSD-95 and Gephyrin, which reside in excitatory and inhibitory synapses, respectively, were both elevated, and their ratio was not affected by apoE4. Electroretinogram (ERG recordings revealed significant attenuation of mixed rod-cone responses in dark-adapted eyes of apoE4 mice. These findings suggest that the reduced ERG response in the apoE4 mice may be related to the observed decrease in the retinal nerve terminals and that the retina could be used as a novel model for non-invasive monitoring of the effects of apoE4 on the CNS.

  11. Folate targeted polymeric &apos;green&apos; nanotherapy for cancer

    Energy Technology Data Exchange (ETDEWEB)

    Narayanan, Sreeja; Binulal, N S; Mony, Ullas; Manzoor, Koyakutty; Nair, Shantikumar; Menon, Deepthy, E-mail: [Amrita Center for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi-682 041, Kerala (India)


    The concept of &apos;green&apos; chemotherapy by employing targeted nanoparticle mediated delivery to enhance the efficacy of phytomedicines is reported. Poly (lactide-co-glycolide) (PLGA) nanoparticles encapsulating a well known nutraceutical namely, grape seed extract (GSE)-&apos;NanoGSE&apos;-was prepared by a nanoprecipitation technique. The drug-loaded nanoparticles of size {approx} 100 nm exhibited high colloidal stability at physiological pH. Molecular receptor targeting of this nanophytomedicine against folate receptor over-expressing cancers was demonstrated in vitro by conjugation with a potential cancer targeting ligand, folic acid (FA). Fluorescence microscopy and flow cytometry data showed highly specific cellular uptake of FA conjugated NanoGSE on folate receptor positive cancer cells. Studies were also conducted to investigate the efficiency of targeted (FA conjugated) versus non-targeted (non-FA conjugated) nanoformulations in causing cancer cell death. The IC{sub 50} values were lowered by a factor of {approx} 3 for FA-NanoGSE compared to the free drug, indicating substantially enhanced bioavailability to the tumor cells, sparing the normal ones. Receptor targeting of FA-NanoGSE resulted in a significant increase in apoptotic index, which was also quantified by flow cytometry and fluorescence microscopy. This in vitro study provides a basis for the use of nanoparticle mediated delivery of anticancer nutraceuticals to enhance bioavailability and effectively target cancer by a &apos;green&apos; approach.

  12. Oxidative lixiviation of pitchblende and precipitation of uranium with hydrogen; Lixiviation oxydante des pechblendes et precipitation de l&apos;uranium par l&apos;hydrogene

    Energy Technology Data Exchange (ETDEWEB)

    Mouret, P. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Balaceanu, J.C.; Coussemant, F. [Institut Francais du Petrole (IFP), 92 - Rueil-Malmaison (France)


    Earlier work on the preparation of uranium by F.A. Forward and his colleagues has shown the possibilities presented by oxidative lixiviation of ores in a carbonate medium, and the catalytic reduction of uranyl carbonate solutions by hydrogen. The carbonate attack is of considerable interest because of the selectivity of the uranium dissolution, which means it can be applied particularly to the treatment of low grade ores with a reduced consumption of cheap reagents. The subsequent reduction with hydrogen is of the same nature, and not only enabl