Specificity determinants in the interaction of apolipoprotein(a) kringles with tetranectin and LDL.

Science.gov (United States)

Caterer, Nigel R; Graversen, Jonas H; Jacobsen, Christian; Moestrup, Søren K; Sigurskjold, Bent W; Etzerodt, Michael; Thøgersen, Hans C

2002-11-01

Lipoprotein(a) is composed of low density lipoprotein and apolipoprotein(a). Apolipoprotein(a) has evolved from plasminogen and contains 10 different plasminogen kringle 4 homologous domains [KIV(1-110)]. Previous studies indicated that lipoprotein(a) non-covalently binds the N-terminal region of lipoprotein B100 and the plasminogen kringle 4 binding plasma protein tetranectin. In this study recombinant KIV(2), KIV(7) and KIV(10) derived from apolipoprotein(a) were produced in E. coli and the binding to tetranectin and low density lipoprotein was examined. Only KIV(10) bound to tetranectin and binding was similar to that of plasminogen kringle 4 to tetranectin. Only KIV(7) bound to LDL. In order to identify the residues responsible for the difference in specificity between KIV(7) and KIV(10), a number of surface-exposed residues located around the lysine binding clefts were exchanged. Ligand binding analysis of these derivatives showed that Y62, and to a minor extent W32 and E56, of KIV(7) are important for LDL binding to KIV(7), whereas R32 and D56 of KIV(10) are required for tetranectin binding of KIV(10).

A strategy for solubilizing delipidated apolipoprotein with lysophosphatidylcholine and reconstitution with phosphatidylcholine

International Nuclear Information System (INIS)

Kawooya, J.K.; Wells, M.A.; Law, J.H.

1989-01-01

The apolipoproteins of insect lipophorin were dissociated in guanidinium chloride and isolated by gel permeation chromatography. Over 98% of the total lipid in lipophorin was associated with apolipophorin I (apoLp-I), thus suggesting this apolipoprotein to be the lipid binding component of the particle. ApoLp-I was delipidated with ethanol/ether and solubilized in buffer that contained radioactive lysophosphatidylcholine ([ 3 H]LPC) above the critical micellar concentration. Sonic irradiation of radioactive phosphatidylcholine ([ 14 C]PC) with [ 3 H]LPC-solubilized apoLp-I at a molar ratio of 318 resulted in reconstituted lipophorin I (RLp-I). [ 3 H]LPC was bound to fatty acid free bovine serum albumin and was separated from RLp-I by density gradient ultracentrifugation and gel permeation chromatography. Negatively stained RLp-I particles were quasispherical with an average radius of 55 angstrom, and their overall morphology and secondary structure were similar to those of native hemolymph lipophorin. The RLp-I particle had a ρ = 1.137 g/mL, a M r ∼ 5.2 x 10 5 , and a [ 14 C]PC:apoLp-I molar ratio of 308. From the compositional analysis, molecular size, trypsinization, and lipolysis with phospholipase A 2 , the authors concluded that each RLp-I particle contained one molecule of apoLp-I and a monomolecular layer of [ 14 C]PC. When injected into the hemolymph of adult moths in vivo, RLp-I was loaded with lipid, as judged by a decrease in its density both in the presence and in the absence of adipokinetic hormone. The similarities in morphology and immunology of RLp-I and native lipophorin, together with the ability of RLp-I to load lipid, suggest that reconstituted lipophorins may serve as models to probe lipophorin structure and function

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

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Bin Hong

2012-06-01

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.

Comparison of apolipoprotein (apoB/apoA-I and lipoprotein (total cholesterol/HDL ratio determinants. Focus on obesity, diet and alcohol intake.

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Gianluca Tognon

Full Text Available 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.

Metabolism of apolipoproteins A-I and A-II in human high-density lipoprotein: a mathematical approach for analysis of their specific activity decay curves

International Nuclear Information System (INIS)

Atmeh, R.F.

1987-01-01

The differential rate equations describing the compartmental model of human high-density lipoprotein (HDL) were integrated by means of Laplace transforms and an exponential equation was obtained for each of the three compartments. These equations were used to fit the observed plasma decay data and give estimates for the rate constants of the system by means of a written computer program. Furthermore, these estimates were used to calculate the exponential constants of the integrated equations. Consequently, the amount of label in any of the intravascular, extravascular, and urine compartments can be calculated as a fraction of the original dose of label at any time point. This method was tested using data for the (AI)HDL subclass because it contains only apolipoprotein A-I as the major apolipoprotein and does not contain apolipoprotein A-II. The calculated plasma and urine radioactivity data were compared with the experimentally obtained data from two normolipoproteinemic subjects and found to be in good agreement. The significance of this method is its application to the analysis of the decay data of the individual apolipoproteins of (AI + AII) HDL subclass where the urinary radioactivity data resulting from the individual apolipoprotein breakdown on the native particle cannot be measured experimentally at present. Such data are essential for the detailed calculation of the kinetic parameters of these apolipoproteins

Effect of an isoenergetic traditional Mediterranean diet on apolipoprotein A-I kinetic in men with metabolic syndrome

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The impact of the Mediterranean diet (MedDiet) on high-density lipoprotein (HDL) kinetics has not been studied to date. The objective of this study was therefore to investigate the effect of the MedDiet in the absence of changes in body weight on apolipoprotein (apo) A-I kinetic in men with metaboli...

Iowa Mutant Apolipoprotein A-I (ApoA-IIowa) Fibrils Target Lysosomes.

Science.gov (United States)

Kameyama, Hirokazu; Nakajima, Hiroyuki; Nishitsuji, Kazuchika; Mikawa, Shiho; Uchimura, Kenji; Kobayashi, Norihiro; Okuhira, Keiichiro; Saito, Hiroyuki; Sakashita, Naomi

2016-07-28

The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIowa) is the first mutation that was associated with familial AApoA1 amyloidosis. The N-terminal fragments (amino acid residues 1-83) of apoA-I containing this mutation deposit as amyloid fibrils in patients' tissues and organs, but the mechanisms of cellular degradation and cytotoxicity have not yet been clarified. In this study, we demonstrated degradation of apoA-IIowa fibrils via the autophagy-lysosomal pathway in human embryonic kidney 293 cells. ApoA-IIowa fibrils induced an increase in lysosomal pH and the cytosolic release of the toxic lysosomal protease cathepsin B. The mitochondrial dysfunction caused by apoA-IIowa fibrils depended on cathepsin B and was ameliorated by increasing the degradation of apoA-IIowa fibrils. Thus, although apoA-IIowa fibril transport to lysosomes and fibril degradation in lysosomes may have occurred, the presence of an excess number of apoA-IIowa fibrils, more than the lysosomes could degrade, may be detrimental to cells. Our results thus provide evidence that the target of apoA-IIowa fibrils is lysosomes, and we thereby gained a novel insight into the mechanism of AApoA1 amyloidosis.

NcoI dimorphic site located 8kb 3' to the human apolipoprotein AIV (APOA4) gene

Energy Technology Data Exchange (ETDEWEB)

Coleman, R T; Malloy, M J; Kane, J P; Frossard, P M

1988-02-11

pA4C3 a 0.5kb fragment from the 3' end of the human apolipoprotein AIV cDNA was isolated from a human intestine cDNA library and cloned into the EcoRI site of the plasmid pUC18. NcoI (CCATGG) (New England Biolabs) detects a single two-allele polymorphism with a band at either 18.6kb or at 12.6kb. The human apolipoprotein AI-CIII-AIV gene complex has been assigned to the long arm of chromosome 11 by Southern blot analysis of human-Chinese hamster cell hybrids. Co-dominant segregation was demonstrated in one family of six individuals.

Abnormal histopathology, fat percent and hepatic apolipoprotein A I and apolipoprotein B100 mRNA expression in fatty liver hemorrhagic syndrome and their improvement by soybean lecithin.

Science.gov (United States)

Song, Yalu; Ruan, Jiming; Luo, Junrong; Wang, Tiancheng; Yang, Fei; Cao, Huabin; Huang, Jianzhen; Hu, Guoliang

2017-10-01

To investigate the etiopathogenesis of fatty liver hemorrhagic syndrome (FLHS) and the protective effects of soybean lecithin against FLHS in laying hens, 135 healthy 300-day-old Hyline laying hens were randomly divided into groups: control (group 1), diseased (group 2), and protected (group 3). Each group contained 45 layers with 3 replicates. The birds in these 3 groups were fed a control diet, a high-energy/low-protein (HELP) diet or the HELP diet supplemented with 3% soybean lecithin instead of maize. The fat percent in the liver was calculated. Histopathological changes in the liver were determined by staining, and the mRNA expression levels of apolipoproteinA I (apoA I) and apolipoprotein B100 (apoB100) in the liver were determined by RT-PCR. The results showed that the fat percent in the liver of group 2 was much higher (P steatosis in the liver cell on d 30 and 60. The mRNA expression levels of apoA I and apoB100 in the livers were variable throughout the experiment. The expression level of apoA I in group 2 significantly decreased on d 60 (P < 0.05); the expression level of apoB100 slightly increased on d 30 in group 2, while it sharply decreased on d 60. Compared to group 1, the expression level of apoB100 showed no significant difference in group 3 (P < 0.05). This study indicated that FLHS induced pathological changes and abnormal expression of apoA I and apoB100 in the livers of laying hens and that soybean lecithin alleviated these abnormal changes. © 2017 Poultry Science Association Inc.

Targeting nanodisks via a single chain variable antibody - Apolipoprotein chimera

International Nuclear Information System (INIS)

Iovannisci, David M.; Beckstead, Jennifer A.; Ryan, Robert O.

2009-01-01

Nanodisks (ND) are nanometer scale complexes of phospholipid and apolipoprotein that have been shown to function as drug delivery vehicles. ND harboring significant quantities of the antifungal agent, amphotericin B, or the bioactive isoprenoid, all trans retinoic acid, have been generated and characterized. As currently formulated, ND possess limited targeting capability. In this study, we constructed a single chain variable antibody (scFv).apolipoprotein chimera and assessed the ability of this fusion protein to form ND and recognize the antigen to which the scFv is directed. Data obtained revealed that α-vimentin scFv.apolipoprotein A-I is functional in ND formation and antigen recognition, opening the door to the use of such chimeras in targeting drug-enriched ND to specific tissues.

Secretion of apolipoproteins A-I and B by HepG2 cells: regulation by substrates and metabolic inhibitors.

Science.gov (United States)

Kempen, H J; Imbach, A P; Giller, T; Neumann, W J; Hennes, U; Nakada, N

1995-08-01

It was the aim of this study to i) compare the effects of glucose and other hexoses with that of oleate on secretion of apolipoproteins (apos) A-I and B by HepG2 cells, and ii) document the effect of various metabolic inhibitors on the secretion of these apos in the absence or presence of extra glucose/oleate. i) The addition of 10 mM glucose increased secretion of apoA-I and apoB, as measured by enzyme immunoassay, by about 60% when cells were incubated for 48 h in DMEM + 10% fetal calf serum. The addition of extra glucose also increased the mRNA levels for these apos. Increased radioactivity was also found in these apolipoproteins by immunoprecipitation after metabolic labeling with [35S]methionine for 48 h. However, in a pulse-chase experiment (15 min labeling, 2 h chase), glucose was found to increase apoA-I synthesis but not apoB synthesis. More labeled apoB appeared in the medium during the chase because glucose inhibited its intracellular degradation. The effect of glucose on secretion of these apos could be mimicked by fructose and mannose but not by 6-deoxyglucose, showing that the hexoses must enter the cells and be phosphorylated. In contrast, the addition of 0.5 mM oleate had a weak inhibitory effect on secretion of apoA-I whereas it increased the secretion of apoB by more than twofold. The combination of 10 mM glucose and 0.5 mM oleate had no greater effect than glucose alone on apoA-I secretion but increased apoB secretion by fourfold. ii) Inhibiting glycolysis (by glucosamine) lowered secretion of both apoA-I and apoB, while inhibiting lipogenesis (using 8-Br-cyclic AMP or 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA)) did not affect apoA-I secretion but clearly decreased that of apoB. However, the inhibitory effect of TOFA on apoB secretion was much smaller in the presence of 0.5 mM oleate instead of extra glucose. Actinomycin-D and cycloheximide strongly suppressed the stimulatory effect of glucose on secretion of both apolipoproteins

Influence of Peripheral Artery Disease and Statin Therapy on Apolipoprotein Profiles

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Andrew W. Gardner

2013-01-01

Full Text Available Apolipoprotein B is a stronger predictor of myocardial infarction than LDL cholesterol, and it is inversely related to physical activity and modifiable with exercise training. As such, apolipoprotein measures may be of particular relevance for subjects with PAD and claudication. We compared plasma apolipoprotein profiles in 29 subjects with peripheral artery disease (PAD and intermittent claudication and in 39 control subjects. Furthermore, we compared the plasma apolipoprotein profiles of subjects with PAD either treated (n=17 or untreated (n=12 with statin medications. For the apolipoprotein subparticle analyses, subjects with PAD had higher age-adjusted Lp-B:C (P<0.05 and lower values of Lp-A-I:A-II (P<0.05 than controls. The PAD group taking statins had lower age-adjusted values for apoB (P<0.05, Lp-A-II:B:C:D:E (P<0.05, Lp-B:E + Lp-B:C:E (P<0.05, Lp-B:C (P<0.05, and Lp-A-I (P<0.05 than the untreated PAD group. Subjects with PAD have impaired apolipoprotein profiles than controls, characterized by Lp-B:C and Lp-A-I:A-II. Furthermore, subjects with PAD on statin medications have a more favorable risk profile, particularly noted in multiple apolipoprotein subparticles. The efficacy of statin therapy to improve cardiovascular risk appears more evident in the apolipoprotein sub-particle profile than in the more traditional lipid profile of subjects with PAD and claudication. This trial is registered with ClinicalTrials.gov NCT00618670.

A model of lipid-free apolipoprotein A-I revealed by iterative molecular dynamics simulation.

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Xing Zhang

Full Text Available Apolipoprotein A-I (apo A-I, the major protein component of high-density lipoprotein, has been proven inversely correlated to cardiovascular risk in past decades. The lipid-free state of apo A-I is the initial stage which binds to lipids forming high-density lipoprotein. Molecular models of lipid-free apo A-I have been reported by methods like X-ray crystallography and chemical cross-linking/mass spectrometry (CCL/MS. Through structural analysis we found that those current models had limited consistency with other experimental results, such as those from hydrogen exchange with mass spectrometry. Through molecular dynamics simulations, we also found those models could not reach a stable equilibrium state. Therefore, by integrating various experimental results, we proposed a new structural model for lipid-free apo A-I, which contains a bundled four-helix N-terminal domain (1-192 that forms a variable hydrophobic groove and a mobile short hairpin C-terminal domain (193-243. This model exhibits an equilibrium state through molecular dynamics simulation and is consistent with most of the experimental results known from CCL/MS on lysine pairs, fluorescence resonance energy transfer and hydrogen exchange. This solution-state lipid-free apo A-I model may elucidate the possible conformational transitions of apo A-I binding with lipids in high-density lipoprotein formation.

Transfer of C-terminal residues of human apolipoprotein A-I to insect apolipophorin III creates a two-domain chimeric protein with enhanced lipid binding activity.

Science.gov (United States)

Horn, James V C; Ellena, Rachel A; Tran, Jesse J; Beck, Wendy H J; Narayanaswami, Vasanthy; Weers, Paul M M

2017-08-01

Apolipophorin III (apoLp-III) is an insect apolipoprotein (18kDa) that comprises a single five-helix bundle domain. In contrast, human apolipoprotein A-I (apoA-I) is a 28kDa two-domain protein: an α-helical N-terminal domain (residues 1-189) and a less structured C-terminal domain (residues 190-243). To better understand the apolipoprotein domain organization, a novel chimeric protein was engineered by attaching residues 179 to 243 of apoA-I to the C-terminal end of apoLp-III. The apoLp-III/apoA-I chimera was successfully expressed and purified in E. coli. Western blot analysis and mass spectrometry confirmed the presence of the C-terminal domain of apoA-I within the chimera. While parent apoLp-III did not self-associate, the chimera formed oligomers similar to apoA-I. The chimera displayed a lower α-helical content, but the stability remained similar compared to apoLp-III, consistent with the addition of a less structured domain. The chimera was able to solubilize phospholipid vesicles at a significantly higher rate compared to apoLp-III, approaching that of apoA-I. The chimera was more effective in protecting phospholipase C-treated low density lipoprotein from aggregation compared to apoLp-III. In addition, binding interaction of the chimera with phosphatidylglycerol vesicles and lipopolysaccharides was considerably improved compared to apoLp-III. Thus, addition of the C-terminal domain of apoA-I to apoLp-III created a two-domain protein, with self-association, lipid and lipopolysaccharide binding properties similar to apoA-I. The apoA-I like behavior of the chimera indicate that these properties are independent from residues residing in the N-terminal domain of apoA-I, and that they can be transferred from apoA-I to apoLp-III. Copyright © 2017 Elsevier B.V. All rights reserved.

High yield of recombinant human Apolipoprotein A-I expressed in Pichia pastoris by using mixed-mode chromatography.

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Narasimhan Janakiraman, Vignesh; Noubhani, Abdelmajid; Venkataraman, Krishnan; Vijayalakshmi, Mookambeswaran; Santarelli, Xavier

2016-01-01

A vast majority of the cardioprotective properties exhibited by High-Density Lipoprotein (HDL) is mediated by its major protein component Apolipoprotein A-I (ApoA1). In order to develop a simplified bioprocess for producing recombinant human Apolipoprotein A-I (rhApoA1) in its near-native form, rhApoA1was expressed without the use of an affinity tag in view of its potential therapeutic applications. Expressed in Pichia pastoris at expression levels of 58.2 mg ApoA1 per litre of culture in a reproducible manner, the target protein was purified by mixed-mode chromatography using Capto™ MMC ligand with a purity and recovery of 84% and 68%, respectively. ApoA1 purification was scaled up to Mixed-mode Expanded Bed Adsorption chromatography to establish an 'on-line' process for the efficient capture of rhApoA1 directly from the P. pastoris expression broth. A polishing step using anion exchange chromatography enabled the recovery of ApoA1 up to 96% purity. Purified ApoA1 was identified and verified by RPLC-ESI-Q-TOF mass spectrometry. This two-step process would reduce processing times and therefore costs in comparison to the twelve-step procedure currently used for recovering rhApoA1 from P. pastoris. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Apolipoprotein nanodiscs with telodendrimer

Energy Technology Data Exchange (ETDEWEB)

Luo, Juntao; He, Wei; Lam, Kit S.; Henderson, Paul; Coleman, Matthew; Cheng, R. Holland; Xing, Li

2017-05-09

The present invention provides a nanodisc with a membrane scaffold protein. The nanodisc includes a membrane scaffold protein, a telodendrimer and a lipid. The membrane scaffold protein can be apolipoprotein. The telodendrimer has the general formula PEG-L-D-(R).sub.n, wherein D is a dendritic polymer; L is a bond or a linker linked to the focal point group of the dendritic polymer; each PEG is a poly(ethylene glycol) polymer; each R is and end group of the dendritic polymer, or and end group with a covalently bound hydrophobic group, hydrophilic group, amphiphilic compound, or drug; and subscript n is an integer from 2 to 20. Cell free methods of making the nanodiscs are also provided.

Affinity of serum apolipoproteins for lipid monolayers

International Nuclear Information System (INIS)

Ibdah, J.A.

1987-01-01

The effects of lipid composition and packing as well as the structure of the protein on the affinities of apolipoproteins for lipid monolayers have been investigated. The adsorption of 14 C-reductively methylated human apolipoproteins A-I and A-II at saturating subphase concentrations to monolayers prepared with synthetic lipids or lipoprotein surface lipids spread at various initial surface pressures has been studied. The adsorption of apolipoproteins is monitored by following the surface radioactivity using a gas flow counter and Wilhelmy plate, respectively. The physical states of the lipid monolayers are evaluated by measurement of the surface pressure-molecular area isotherms using a Langmuir-Adam surface balance. The probable helical regions in various apolipoproteins have been predicted using a secondary structure analysis computer program. The mean residue hydrophobicity and mean residue hydrophobic moment for the predicted helical segments have been calculated. The surface properties of synthetic peptides which are amphipathic helix analogs have been investigated at the air-water and lipid-water interfaces

Fibrate-modulated expression of fibrinogen, plasminogen activator inhibitor-1 and apolipoprotein A-I in cultured cynomolgus monkey hepatocytes. Role of the peroxisome proliferator-activated receptor-α

NARCIS (Netherlands)

Kockx, M.; Princen, H.M.G.; Kooistra, T.

1998-01-01

Fibrates are used to lower plasma triglycerides and cholesterol levels in hyperlipidemic patients. In addition, fibrates have been found to alter the plasma concentrations of fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and apolipoprotein A-I (apo A-I). We have investigated the in vitro

Caveolin-1-mediated apolipoprotein A-I membrane binding sites are not required for cholesterol efflux.

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Soazig Le Lay

Full Text Available Caveolin-1 (Cav1, a structural protein required for the formation of invaginated membrane domains known as caveolae, has been implicated in cholesterol trafficking and homeostasis. Here we investigated the contribution of Cav1 to apolipoprotein A-I (apoA-I cell surface binding and intracellular processing using mouse embryonic fibroblasts (MEFs derived from wild type (WT or Cav1-deficient (Cav1(-/- animals. We found that cells expressing Cav1 have 2.6-fold more apoA-I binding sites than Cav1(-/- cells although these additional binding sites are not associated with detergent-free lipid rafts. Further, Cav1-mediated binding targets apoA-I for internalization and degradation and these processes are not correlated to cholesterol efflux. Despite lower apoA-I binding, cholesterol efflux from Cav1(-/- MEFs is 1.7-fold higher than from WT MEFs. Stimulation of ABCA1 expression with an LXR agonist enhances cholesterol efflux from both WT and Cav1(-/- cells without increasing apoA-I surface binding or affecting apoA-I processing. Our results indicate that there are at least two independent lipid binding sites for apoA-I; Cav1-mediated apoA-I surface binding and uptake is not linked to cholesterol efflux, indicating that membrane domains other than caveolae regulate ABCA1-mediated cholesterol efflux.

A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E–Knockout Mice

Science.gov (United States)

Sakurai, Toshihiro; Sakurai-Ikuta, Akiko; Sviridov, Denis; Freeman, Lita; Ahsan, Lusana; Remaley, Alan T.

2015-01-01

Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as possible new agents for the treatment of cardiovascular disease based on their ability to promote cholesterol efflux and their other beneficial antiatherogenic properties. Many of these peptides, however, have been reported to cause transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein lipase (LPL). We describe a novel bihelical amphipathic peptide (C-II-a) that contains an amphipathic helix (18A) for binding to lipoproteins and stimulating cholesterol efflux as well as a motif based on the last helix of apolipoprotein C-II (apoC-II) that activates lipolysis by LPL. The C-II-a peptide promoted cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to be comparable to the full-length apoC-II protein in activating lipolysis by LPL. When added to serum from a patient with apoC-II deficiency, it restored normal levels of LPL-induced lipolysis and also enhanced lipolysis in serum from patients with type IV and V hypertriglyceridemia. Intravenous injection of C-II-a (30 mg/kg) in apolipoprotein E–knockout mice resulted in a significant reduction of plasma cholesterol and triglycerides of 38 ± 6% and 85 ± 7%, respectively, at 4 hours. When coinjected with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg) peptide was found to completely block the hypertriglyceridemic effect of the 5A peptide in C57Bl/6 mice. In summary, C-II-a is a novel peptide based on apoC-II, which promotes cholesterol efflux and lipolysis and may therefore be useful for the treatment of apoC-II deficiency and other forms of hypertriglyceridemia. PMID:25395590

Isolation and characterization of human apolipoprotein M-containing lipoproteins

DEFF Research Database (Denmark)

Christoffersen, Christina; Nielsen, Lars Bo; Axler, Olof

2006-01-01

Apolipoprotein M (apoM) is a novel apolipoprotein with unknown function. In this study, we established a method for isolating apoM-containing lipoproteins and studied their composition and the effect of apoM on HDL function. ApoM-containing lipoproteins were isolated from human plasma...... with immunoaffinity chromatography and compared with lipoproteins lacking apoM. The apoM-containing lipoproteins were predominantly of HDL size; approximately 5% of the total HDL population contained apoM. Mass spectrometry showed that the apoM-containing lipoproteins also contained apoJ, apoA-I, apoA-II, apoC-I, apo...

Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis

NARCIS (Netherlands)

Bisoendial, Radjesh; Tabet, Fatiha; Tak, Paul P.; Petrides, Francine; Cuesta Torres, Luisa F.; Hou, Liming; Cook, Adam; Barter, Philip J.; Weninger, Wolfgang; Rye, Kerry-Anne

2015-01-01

Lymphatic endothelial dysfunction underlies the pathogenesis of many chronic inflammatory disorders. The proinflammatory cytokine tumor necrosis factor (TNF) is known for its role in disrupting the function of the lymphatic vasculature. This study investigates the ability of apolipoprotein (apo)

Apolipoprotein A-I metabolism in cynomolgus monkey. Identification and characterization of beta-migrating pools

International Nuclear Information System (INIS)

Melchior, G.W.; Castle, C.K.

1989-01-01

Fresh plasma from control (C) and hypercholesterolemic (HC) cynomolgus monkeys was analyzed by agarose electrophoresis-immunoblotting with antibody to cynomolgus monkey apolipoprotein (apo) A-I. Two bands were evident on the autoradiogram: an alpha-migrating band (high density lipoprotein) and a beta-migrating band that comigrated exactly with cynomolgus monkey low density lipoprotein (LDL). The presence of beta-migrating apo A-I in the plasma of these monkeys was confirmed by Geon-Pevikon preparative electrophoresis, crossed immunoelectrophoresis, and isotope dilution studies in which radiolabeled apo A-I was found to equilibrate also with alpha- and beta-migrating pools of apo A-I in the plasma. Subfractionation of C and HC plasma by agarose column chromatography (Bio-Gel A-0.5M and A-15M) followed by agarose electrophoresis-immunoblotting indicated that the beta-migrating apo A-I in C was relatively homogeneous and eluted with proteins of Mr approximately 50 kD [apo A-I(50 kD)], whereas two beta-migrating fractions were identified in HC, one that eluted with the 50-kD proteins, and the other that eluted in the LDL Mr range [apo A-I(LDL)]. The apo A-I(LDL) was precipitated by antibody to cynomolgus monkey apo B. The apo A-I(50 kD) accounted for 5 +/- 1% (mean +/- SD) of the plasma apo A-I in C plasma, and 15 +/- 7% in HC plasma. No apo A-I(LDL) was detected in C plasma, but that fraction accounted for 9 +/- 7% of the apo A-I in HC plasma. These data establish the presence of multiple pools of apo A-I in the cynomolgus monkey, which must be taken into consideration in any comprehensive model of apo A-I metabolism in this species

Multiple system atrophy and apolipoprotein E.

Science.gov (United States)

Ogaki, Kotaro; Martens, Yuka A; Heckman, Michael G; Koga, Shunsuke; Labbé, Catherine; Lorenzo-Betancor, Oswaldo; Wernick, Anna I; Walton, Ronald L; Soto, Alexandra I; Vargas, Emily R; Nielsen, Henrietta M; Fujioka, Shinsuke; Kanekiyo, Takahisa; Uitti, Ryan J; van Gerpen, Jay A; Cheshire, William P; Wszolek, Zbigniew K; Low, Phillip A; Singer, Wolfgang; Dickson, Dennis W; Bu, Guojun; Ross, Owen A

2018-04-01

Dysregulation of the specialized lipid metabolism involved in myelin synthesis and maintenance by oligodendrocytes has been associated with the unique neuropathology of MSA. We hypothesized that apolipoprotein E, which is associated with neurodegeneration, may also play a role in the pathogenesis of MSA. This study evaluated genetic associations of Apolipoprotein E alleles with risk of MSA and α-synuclein pathology, and also examined whether apolipoprotein E isoforms differentially affect α-synuclein uptake in a oligodendrocyte cell. One hundred sixty-eight pathologically confirmed MSA patients, 89 clinically diagnosed MSA patients, and 1,277 control subjects were genotyped for Apolipoprotein E. Human oligodendrocyte cell lines were incubated with α-synuclein and recombinant human apolipoprotein E, with internalized α-synuclein imaged by confocal microscopy and cells analyzed by flow cytometry. No significant association with risk of MSA or was observed for either Apolipoprotein E ɛ2 or ɛ4. α-Synuclein burden was also not associated with Apolipoprotein E alleles in the pathologically confirmed patients. Interestingly, in our cell assays, apolipoprotein E ɛ4 significantly reduced α-synuclein uptake in the oligodendrocytic cell line. Despite differential effects of apolipoprotein E isoforms on α-synuclein uptake in a human oligodendrocytic cell, we did not observe a significant association at the Apolipoprotein E locus with risk of MSA or α-synuclein pathology. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Effect of lipid composition and packing on the adsorption of apolipoproteins to lipid monolayers

International Nuclear Information System (INIS)

Ibdah, J.A.; Lund-Katz, S.; Phillips, M.C.

1987-01-01

The monolayer system has been used to study the effects of lipoprotein surface lipid composition and packing on the affinities of apolipoproteins for the surfaces of lipoprotein particles. The adsorption of apolipoproteins injected beneath lipid monolayers prepared with pure lipids or lipoprotein surface lipids is evaluated by monitoring the surface pressure of the film and the surface concentration (Gamma) of 14 C-labelled apolipoprotein. At a given initial film pressure (π/sub i/) there is a higher adsorption of human apo A-I to unsaturated phosphatidylcholine (PC) monolayers compared to saturated PC monolayers (e.g., at π/sub i/ = 10 mN/m, Gamma = 0.35 and 0.06 mg/m 2 for egg PC and distearoyl PC, respectively, with 3 x 10 -4 mg/ml apo A-I in the subphase). In addition, adsorption of apo A-I is less to an egg sphingomyelin monolayer than to an egg PC monolayer. The adsorption of apo A-I to PC monolayers is decreased by addition of cholesterol. Generally, apo A-I adsorption diminishes as the lipid molecular area decreases. Apo A-I adsorbs more to monolayers prepared with HDL 3 surface lipids than with LDL surface lipids. These studies suggest that lipoprotein surface lipid composition and packing are crucial factors influencing the transfer and exchange of apolipoproteins among various lipoprotein classes during metabolism of lipoprotein particles

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

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Allen Anne Marie

2012-12-01

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

Relationship between depression and apolipoproteins A and B: a case-control study

Directory of Open Access Journals (Sweden)

Masoumeh Sadeghi

2011-01-01

Full Text Available OBJECTIVE: To investigate the relation between major depressive disorder and metabolic risk factors of coronary heart disease. INTRODUCTION: Little evidence is available indicating a relationship between major depressive disorder and metabolic risk factors of coronary heart disease such as lipoprotein and apolipoprotein. METHODS: This case-control study included 153 patients with major depressive disorder who fulfilled the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV, and 147 healthy individuals. All participants completed a demographic questionnaire and Hamilton rating scale for depression. Anthropometric characteristics were recorded. Blood samples were taken and total cholesterol, high-and low-density lipoproteins and apolipoproteins A and B were measured. To analyze the data, t-test, χ2 test, Pearson correlation test and linear regression were applied. RESULTS: Depression was a negative predictor of apolipoprotein A (β = -0.328, p<0.01 and positive predictor of apolipoprotein B (β = 0.290, p<0.05. Apolipoprotein A was inversely predicted by total cholesterol (β = -0.269, p<0.05 and positively predicted by high-density lipoprotein (β = 0.401, p<0.01. Also, low-density lipoprotein was a predictor of apolipoprotein B (β = 0.340, p<0.01. The severity of depression was correlated with the increment in serum apolipoprotein B levels and the decrement in serum apolipoprotein A level. CONCLUSION: In view of the relationship between apolipoproteins A and B and depression, it would seem that screening of these metabolic risk factors besides psychological interventions is necessary in depressed patients

Clinical chemistry of common apolipoprotein E isoforms

NARCIS (Netherlands)

Brouwer, DAJ; vanDoormaal, JJ; Muskiet, FAJ

1996-01-01

Apolipoprotein E plays a central role in clearance of lipoprotein remnants by serving as a ligand for low-density lipoprotein and apolipoprotein E receptors. Three common alleles (apolipoprotein E(2), E(3) and E(4)) give rise to six phenotypes. Apolipoprotein E(3) is the ancestral form. Common

A prominent large high-density lipoprotein at birth enriched in apolipoprotein C-I identifies a new group of infancts of lower birth weight and younger gestational age

Energy Technology Data Exchange (ETDEWEB)

Kwiterovich Jr., Peter O.; Cockrill, Steven L.; Virgil, Donna G.; Garrett, Elizabeth; Otvos, James; Knight-Gibson, Carolyn; Alaupovic, Petar; Forte, Trudy; Farwig, Zachlyn N.; Macfarlane, Ronald D.

2003-10-01

Because low birth weight is associated with adverse cardiovascular risk and death in adults, lipoprotein heterogeneity at birth was studied. A prominent, large high-density lipoprotein (HDL) subclass enriched in apolipoprotein C-I (apoC-I) was found in 19 percent of infants, who had significantly lower birth weights and younger gestational ages and distinctly different lipoprotein profiles than infants with undetectable, possible or probable amounts of apoC-I-enriched HDL. An elevated amount of an apoC-I-enriched HDL identifies a new group of low birth weight infants.

The paradox of high apolipoprotein A-I levels independently predicting incident type-2 diabetes among Turks.

Science.gov (United States)

Onat, A; Hergenç, G; Bulur, S; Uğur, M; Küçükdurmaz, Z; Can, G

2010-06-25

Predictive value of apolipoprotein (apo) A-I for incident hypertension, metabolic syndrome (MetS), type 2 diabetes (DM) and coronary heart disease (CHD) needs further exploration. A representative sample of Turkish adults was studied with this purpose prospectively. Sex-specific apoA-I tertiles were examined regarding cardiometabolic risk. A total of 1044 men and 1067 women (aged 49+/-12 years at baseline) were followed up over 7.4 years. High serum apoA-I levels were significantly associated in multivariable analysis with female sex, aging, alcohol intake, (inversely) cigarette smoking and, in women, with systolic blood pressure. Risk of diabetes was predicted in logistic regression in both genders by top versus bottom apoA-I tertile (RR 1.98; [95%CI 1.31; 3.0]), additive to age, body mass index (BMI), C-reactive protein (CRP), HDL-cholesterol and lipid lowering drugs. By adding sex hormone-binding globulin to the model in a subset of the sample, the association between high apoA-I and incident diabetes was attenuated only in women. ApoA-I tertiles tended to be positively associated also with hypertension and CHD only in women but this did not reach significance. High compared with low serum apoA-I levels nearly double the risk for incident diabetes, additively to age, BMI, CRP, HDL-cholesterol among Turks. Systemic inflammation concomitant with prevailing MetS might turn apoA-I into proinflammatory particles. Copyright 2008 Elsevier Ireland Ltd. All rights reserved.

Expression of human apolipoprotein A-I epitopes in high density lipoproteins and in serum

International Nuclear Information System (INIS)

Marcel, Y.L.; Jewer, D.; Vezina, C.; Milthorp, P.; Weech, P.K.

1987-01-01

The expression and immunoreactivity of apolipoprotein (apo) A-I epitopes in high density lipoproteins (HDL) and serum has been investigated using two series of monoclonal antibodies (Mabs) which have been described elsewhere. Series 1 Mabs, identified as 3D4, 6B8, and 5G6, were obtained by immunization and screening with apoA-I, and series 2 Mabs, identified as 2F1, 4H1, 3G10, 4F7, and 5F6, were obtained by immunization and screening with HDL. These Mabs were characterized with respect to their binding to HDL particles in solution. In series 2 Mabs, 2F1, 3G10, and 4F7, which react with apoA-I CNBr-fragments 1 and 2, could precipitate 100% of 125 I-labeled HDL, while 4H1 and 5F6, which react with CNBr fragments 1 and 3, precipitated 90 and 60% of 125 I-labeled HDL, respectively. Therefore, three distinct epitopes mapped to CNBr fragments 1 and 2 have been identified which are expressed on all HDL particles, indicating that several antigenic do mains exist on apoA-I which have the same conformation on all apoA-I-containing lipoproteins. The Mabs reacting at these sites have significantly higher affinity constants for 125 I-labeled HDL than those that failed to precipitate 100% of HDL. This suggests that the high affinity Mabs react with apoA-I epitopes that are both expressed on all lipoproteins and located in thermo-dynamically stable regions of the molecules. All Mabs from series 1 precipitated 35% or less of 125 I-labeled HDL prepared from freshly collected serum, but the proportion of HDL particles expressing the epitopes for these Mabs doubled or more upon serum storage at 4 degrees C. The time course of the alteration of apoA-I antigen in vitro was measured in three normolipemic donors

Lower Bounds for Sorted Geometric Queries in the I/O Model

DEFF Research Database (Denmark)

Afshani, Peyman; Zeh, Norbert

2012-01-01

. This is highly relevant in an I/O context because storing a massive data set in a superlinear-space data structure is often infeasible. We also prove that answering queries using I/Os requires space, where N is the input size, B is the block size, and M is the size of the main memory. This bound is unlikely...... to be optimal and in fact we can show that, for a particular class of “persistence-based” data structures, the space lower bound can be improved to Ω(N2 / MO(1)). Both these lower bounds are a first step towards understanding the complexity of sorted geometric query problems. All our lower bounds assume...

Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

DEFF Research Database (Denmark)

Bentzen, J.; Poulsen, P.; Vaag, A.

2003-01-01

The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco...... on the insulin-to-glucose ratio (p = 0.04), and E4154K (EcoRI RFLP) influenced HOMAbeta (p = 0.04). Significant interactions were observed between genotype in T71I (ApaLI RFLP), A591V (AluI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI RFLP) and glucose tolerance on lipid-related parameters (0.03

Apolipoprotein(a) phenotypes and lipoprotein(a) concentrations in patients with hyperthyroidism

DEFF Research Database (Denmark)

Klausen, I C; Hegedüs, L; Hansen, P S

1995-01-01

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apoB) is attached to a glycoprotein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are ...

Apolipoprotein A-I configuration and cell cholesterol efflux activity of discoidal lipoproteins depend on the reconstitution process.

Science.gov (United States)

Cuellar, Luz Ángela; Prieto, Eduardo Daniel; Cabaleiro, Laura Virginia; Garda, Horacio Alberto

2014-01-01

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. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of fatty acids on the synthesis and secretion of apolipoprotein B by rat hepatocytes

International Nuclear Information System (INIS)

Suresh Kumar, N.; Abraham, Rita; Suresh Kumar, G.; Sudhakaran, P.R.; Kurup, P.A.

1992-01-01

The modulation of apolipoprotein B synthesis and secretion by fatty acids in rat hepatocytes was studied. Maximum apolipoprotein B production was obtained in the case of oleic acid followed by linoleic, stearic and palmitic/linolenic acid when compared to control which was not supplemented with any fatty acids. Oleic acid was found to exert a concentration dependent increase in the secretion of [ 3 H] apolipoprotein B into the medium while that associated with the cell layer was not affected. Pulse chase experiments in the presence of oleic acid showed that it caused an increase in the secretion of apolipoprotein B into the medium. 14 C-acetate incorporation into cholesterol and cholesteryl ester associated with the cell layer and secreted very low density lipoproteins also showed an increase in the presence of oleic acid indicating an increase in cholesterogenesis. The effect of oleic acid on [ 3 H] apolipoprotein B and very low density lipoprotein secretion appeared to be mediated through cholesterol as (i)ketoconazole, an inhibitor of cholesterol synthesis caused significant reduction in the stimulatory effect of oleic acid on apolipoprotein secretion and (ii) mevinolin, another inhibitor of cholesterol synthesis also reversed the stimulatory effect of oleic acid on apolipoprotein B secretion. These results indicated that oleic acid may influence apolipoprotein B synthesis and secretion in hepatocytes probably by affecting cholesterol/cholesteryl ester formation which may be a critical component in the secretion of apolipoprotein B as lipoproteins. (author). 21 refs., 4 figs., 2 tabs

The thyroxine-binding site of human apolipoprotein-A-I: Location in the N-terminal domain

International Nuclear Information System (INIS)

Benvenga, S.; Cahnmann, H.J.; Robbins, J.

1991-01-01

We tested the ability of nine monoclonal antibodies (MAb) against human apolipoprotein-A-I (apoA-I), the 28.3-kDa major apoprotein of high density lipoproteins (HDL), to inhibit its photoaffinity labeling with [125I]T4. Two forms were evaluated: isolated lipid-free apoA-I (Sigma or Calbiochem) and lipid-complexed apoA-I [HDL2, (density, 1.063-1.125 g/ml) and HDL3 (density, 1.125-1.210 g/ml)]. After labeling with 0.5 nM [125I]T4 in the presence of MAb or normal mouse IgG, the products were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent densitometric quantitation of radioactivity associated with the 28.3-kDa band. Group I MAbs, namely those having epitopes in the N-terminal portion of apoA-I, include MAb 16 (epitopes at residues 1-16), 4 and 14 (residues 1-86), and 18 (residues 98-105); group II includes MAbs 7,10, 15, and 17 (epitopes at residues 87-148); group III includes MAb 9 (residues 149-243). All group I MAbs inhibited [125I]T4 binding to isolated apoA-I with this order of potency: MAb 16 greater than MAb 14 greater than MAb 4 greater than MAb 18. In the case of lipid-associated apoA-I, the pattern of hierarchy was variable, presumably related to the known markedly polydisperse nature of HDL, but a constant feature, in contrast to the case of isolated apoA-I, was that MAb 4 was more potent than MAb 14. Group II MAbs gave less than 3% inhibition in both isolated and lipid-complexed apoA-I. Group III MAb 9 either failed to inhibit or gave 18-27% inhibition (one preparation each of HDL2 and HDL3). We conclude that the T4 site of apoA-I is in the N-terminal domain of apoA-I, closer to the epitope for MAb 16 than to that for MAb 18, and that conformational changes occurring when apoA-I is associated with lipids in the HDL particle alter the spatial relationship between some epitopes and the T4 site

27 CFR 73.33 - Am I legally bound by a form I sign electronically?

Science.gov (United States)

2010-04-01

... TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY (CONTINUED) PROCEDURES AND PRACTICES ELECTRONIC SIGNATURES; ELECTRONIC SUBMISSION OF FORMS Electronic Filing of Documents with TTB § 73.33 Am I legally bound... paper document submitted to satisfy the same reporting requirement. Persons using electronic signatures...

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

2016-09-01

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.

Apolipoprotein and lipid abnormalities in chronic liver failure

Directory of Open Access Journals (Sweden)

Spósito A.C.

1997-01-01

Full Text Available Total serum lipids, as well as apolipoproteins A-I (apo A-I and B (apo B, were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P<0.001. Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P<0.001. However, the reduction of HDL cholesterol (HDLc was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P<0.05. We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver

Effects of apolipoproteins on the kinetics of cholesterol exchange

International Nuclear Information System (INIS)

Letizia, J.Y.; Phillips, M.C.

1991-01-01

The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of [ 14 C]cholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid and a trace of [ 14 C]cholesterol were incubated with a 10-fold excess of neutral, acceptor, small unilamellar vesicles. The donor and acceptor particles were separated by chromatogrphy of DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. Apolipoproteins A-I, A-II, reduced and carboxymethylated A-11, and B-100 present in SUV at the same lipid/protein (w/w) ratio all enhance the rate of cholesterol exchange to about the same degree. Cholesterol molecules exchange more rapidly from discoidal complexes. Generally, as the diameter of apoprotein/phospholipid/cholesterol discs decreases, t 1/2 for cholesterol exchange decreases. Since small bilayer discs have a relatively high ratio of boundary to face surface area, cholesterol molecules desorb more rapidly than from larger discs. The modulation of lipid packing by the apoprotein molecules present at the surface of lipoprotein particles affects the rate of cholesterol exchange from such particles

Cerebrospinal Fluid Apolipoprotein E Levels in Delirium

Directory of Open Access Journals (Sweden)

Gideon A. Caplan

2017-07-01

Full Text Available Background/Aims: Delirium and the apolipoprotein E ε4 allele are risk factors for late-onset Alzheimer disease (LOAD, but the connection is unclear. We looked for an association. Methods: Inpatients with delirium (n = 18 were compared with LOAD outpatients (n = 19, assaying blood and cerebrospinal fluid (CSF using multiplex ELISA. Results: The patients with delirium had a higher Confusion Assessment Method (CAM score (5.6 ± 1.2 vs. 0.0 ± 0.0; p < 0.001 and Delirium Index (13.1 ± 4.0 vs. 2.9 ± 1.2; p = 0.001 but a lower Mini-Mental State Examination (MMSE score (14.3 ± 6.8 vs. 20.8 ± 4.6; p = 0.003. There was a reduction in absolute CSF apolipoprotein E level during delirium (median [interquartile range]: 9.55 μg/mL [5.65–15.05] vs. 16.86 μg/mL [14.82–20.88]; p = 0.016 but no differences in apolipoprotein A1, B, C3, H, and J. There were no differences in blood apolipoprotein levels, and no correlations between blood and CSF apolipoprotein levels. CSF apolipoprotein E correlated negatively with the CAM score (r = –0.354; p = 0.034 and Delirium Index (r = –0.341; p = 0.042 but not with the Acute Physiology and Chronic Health Evaluation (APACHE index, or the MMSE or Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE. Conclusion: Reduced CSF apolipoprotein E levels during delirium may be a mechanistic link between two important risk factors for LOAD.

Lipid profile, apolipoprotein A-I and oxidative stress in professional footballers, sedentary individuals, and their relatives.

Science.gov (United States)

Zanella, Aline Margioti; Nakazone, Marcelo Arruda; Pinhel, Marcela Augusta Souza; Souza, Dorotéia Rossi Silva

2011-03-01

To evaluate whether lipid profile (LP), apolipoprotein A-1 (apo A-I) and malondialdehyde (MDA) have any relationship with physical exercise by comparing the groups of footballers (FG) with sedentary individuals (CG) and their relatives (RFG and RCG). Twenty individuals from FG and CG, 60 from RFG, and 57 from RCG were studied. FG showed lower levels of total cholesterol (119.5 ± 37.9 mg/dL), LDL-cholesterol fraction (53.6 ± 30.3), apo A-I (116.7 ± 11.9), and higher level of HDL-cholesterol fraction (HDLc) (49.7 ± 8.5) compared to RFG (148.3 ± 36.9, P = 0.02; 82.4 ± 37.7, P < 0.01; 124.6 ± 10.2, P = 0.03; and 42.7 ± 7.7, P < 0.01; respectively). Moreover, FG had reduced levels of MDA (101.0 ± 77.0 ng/mL) compared to CG (290.0 ± 341.0, P = 0.03) and RFG (209.9 ± 197.5, P = 0.04). These results suggest an association between physical exercise and lower levels of MDA in FG. Physical activity seems to promote beneficial effects on the LP regardless of the genetic influence considering HDLc levels.

Demonstration Of An Abnormality Of Apolipoprotein Ciii And Genetic ...

African Journals Online (AJOL)

Gout is the principal clinical manifestation of hyperuricaemia and leading cause of inflammatory arthritis in adult men. Lipids and apolipoproteins therefore plays an important role in the pathophysiology of the changes seen in hyperuricaemia. We conducted a study on the relationship between APOC3 SstI polymorphism ...

Reduced biliary sterol output with no change in total faecal excretion in mice expressing a human apolipoprotein A-I variant.

Science.gov (United States)

Parolini, Cinzia; Caligari, Silvia; Gilio, Donatella; Manzini, Stefano; Busnelli, Marco; Montagnani, Marco; Locatelli, Marcello; Diani, Erika; Giavarini, Flavio; Caruso, Donatella; Roda, Enrico; Roda, Aldo; Sirtori, Cesare R; Chiesa, Giulia

2012-10-01

Apolipoprotein (apo)A-I(M) (ilano), is a molecular variant of apoA-I(wild-type), associated with dramatically low HDL-cholesterol levels, but no increased risk for cardiovascular disease. In view of the present uncertainties on the role of apoA-I in liver cholesterol removal by way of bile acids and neutral sterols, and of the greater capacity of apoA-I(M) (ilano) to remove arterial cholesterol, biliary sterol metabolism was evaluated in transgenic mice expressing apoA-I(M) (ilano). ApoA-I(M) (ilano) mice were fed a high-cholesterol/high-fat diet, and compared with human apoA-I(wild-type) mice. Plasma lipid levels, hepatic bile flow and composition, hepatic and intestinal cholesterol and bile acid content, and faecal sterol content were measured. Moreover, the expression of hepatic ABCA1, SR-B1 and that of hepatic and intestinal genes involved in bile acid metabolism were evaluated. The dietary treatment led to a strong elevation in HDL-cholesterol levels in A-I(M) (ilano) mice, associated with an increased expression of hepatic ABCA1. ApoA-I(M) (ilano) mice showed lower cholesterol output from the liver compared with apoA-I(wild-type) mice, in the absence of liver sterol accumulation. Faecal excretion of neutral sterols and bile acids was similar in the two mouse lines. In spite of a different response to the dietary challenge, with an increased ABCA1 expression and a lower hepatic cholesterol output in apoA-I(M) (ilano) mice, the net sterol excretion is comparable in the two transgenic lines. © 2012 John Wiley & Sons A/S.

Sex differences in apolipoprotein A1 and nevirapine-induced toxicity

OpenAIRE

Aline Marinho; Clara Dias; Alexandra Antunes; Umbelina Caixas; Teresa Branco; Matilde Marques; Emília Monteiro; Sofia Pereira

2014-01-01

Nevirapine (NVP) is associated with severe liver and skin toxicity through sulfotransferase (SULT) bioactivation of the phase I metabolite 12-hydroxy-NVP [1–3]. The female sex, a well-known risk factor for NVP-induced toxicity, is associated with higher SULT expression [4] and lower plasma levels of 12-hydroxy-NVP [3]. Interestingly, apolipoprotein A1 (ApoA1) increases SULT2B1 activity and ApoA1 synthesis is increased by NVP [5, 6]. Herein, we explore the effect of ApoA1 levels on NVP metabol...

High-density lipoprotein apolipoproteins in urine: I. Characterization in normal subjects and in patients with proteinuria.

Science.gov (United States)

Gomo, Z A; Henderson, L O; Myrick, J E

1988-09-01

A high-resolution two-dimensional electrophoretic method for protein, with silver staining, has been used to characterize and identify urinary high-density-lipoprotein apolipoproteins (HDL-Apos) and their isoforms in healthy subjects and in patients with kidney disease. Analytical techniques based on both molecular mass and ultracentrifugal flotation properties were used to isolate urinary lipoprotein particles with characteristics identical to those of HDL in plasma. HDL-Apos identified in urine of normal subjects and patients with glomerular proteinuria were Apos A-I, A-II, and C. Five isoforms of Apo A-I were present. Immunostaining of electroblotted proteins further confirmed the presence of HDL-Apos in urine. Creatinine clearance rate was decreased in the patients with proteinuria, and ranged from 32.5 to 40 mL/min. Concentrations of cholesterol and triglycerides in serum were greater in the patients' group, whereas mean HDL-cholesterol (0.68, SD 0.10 mmol/L) and Apo A-I (0.953, SD 0.095 g/L) were significantly (each P less than 0.01) lower. Results of this study suggest that measurement of urinary Apo A-I will reflect excretion of HDL in urine.

High-dose recombinant apolipoprotein A-I(milano) mobilizes tissue cholesterol and rapidly reduces plaque lipid and macrophage content in apolipoprotein e-deficient mice. Potential implications for acute plaque stabilization.

Science.gov (United States)

Shah, P K; Yano, J; Reyes, O; Chyu, K Y; Kaul, S; Bisgaier, C L; Drake, S; Cercek, B

2001-06-26

Repeated doses of recombinant apolipoprotein A-I(Milano) phospholipid complex (apoA-I(m)) reduce atherosclerosis and favorably change plaque composition in rabbits and mice. In this study, we tested whether a single high dose of recombinant apoA-I(m) could rapidly mobilize tissue cholesterol and reduce plaque lipid and macrophage content in apoE-deficient mice. High cholesterol-fed, 26-week-old apoE-deficient mice received a single intravenous injection of saline (n=16), 1080 mg/kg dipalmitoylphosphatidylcholine (DPPC; n=14), or 400 mg/kg of recombinant apoA-I(m) complexed with DPPC (1:2.7 weight ratio; n=18). Blood was sampled before and 1 and 48 hours after injection, and aortic root plaques were evaluated for lipid content and macrophage content after oil-red O and immunostaining, respectively. One hour after injection, the plasma cholesterol efflux-promoting capacity was nearly 2-fold higher in recombinant apoA-I(m)-treated mice compared with saline and DPPC-treated mice (P<0.01). Compared with baseline values, serum free cholesterol, an index of tissue cholesterol mobilization, increased 1.6-fold by 1 hour after recombinant apoA-I(m) injection, and it remained significantly elevated at 48 hours (P<0.01). Mice receiving recombinant apoA-I(m) had 40% to 50% lower lipid content (P<0.01) and 29% to 36% lower macrophage content (P<0.05) in their plaques compared with the saline- and DPPC-treated mice, respectively. A single high dose of recombinant apoA-I(m) rapidly mobilizes tissue cholesterol and reduces plaque lipid and macrophage content in apoE-deficient mice. These findings suggest that this strategy could rapidly change plaque composition toward a more stable phenotype.

Polymorphisms in apolipoprotein B and risk of ischemic stroke

DEFF Research Database (Denmark)

Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan Skov

2007-01-01

Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown.......Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown....

OS041. Apolipoprotein A-I protects normal integration of the trophoblast into endothelial cellular networks in an in vitro model of preeclampsia.

Science.gov (United States)

Charlton, F; Xu, B; Makris, A; Hennessy, A; Rye, K-A

2012-07-01

Failure of the trophoblast to appropriately invade uterine spiral arteries is thought to be an initiating event in preeclampsia, a disorder associated with endothelial dysfunction. A dyslipidemia characterised by low plasma levels of high density lipoproteins (HDL) and elevated triglycerides has also been described in preeclampsia. The pro-inflammatory cytokine TNF-α inhibits trophoblast invasion of uterine endothelial cells. Previous work using an in vitro JEG-3 cell/Uterine endothelial cell co-culture model investigated the effect of apoliopoprotein A-I, the main apolipoprotein component of HDL, on trophoblast incorporation into endothelial tubules in the presence and absence of TNF-α. These effects are now investigated using the human invasive trophoblast cell line HTR-8/SVneo. This study asks if apoA-I, which has established anti-inflammatory properties, can protect against the deleterious effect of TNF-α on trophoblast-endothelial cell interactions. The in vitro trophoblast-uterine endothelial cell co-culture model was used to investigate the effect of apoA-I on trophoblast incorporation into endothelial tubules in the presence and absence of TNF-α. Uterine endothelial cells were pre-incubated with lipid free apoA-I (final apoA-I concentration 1 mg/mL) for 16h prior to seeding on matrigel coated plates. Tubules formed within 4h. Fluorescence-labelled HTR-8/SVneo trophoblast cells were then co-cultured with the endothelial cells±TNF-α (final concentration of 0.2ng/mL). Bright field and fluorescent images were captured after 24h. The effect of TNF-α on HTR-8/SVneo cell invasion was quantified with Image J software. Integration of HTR-8/SVneo trophoblast cells into uterine endothelial tubular networks was also imaged using live cell imaging techniques (Zeiss Axiovert). TNF-α inhibited HTR-8/SVneo (trophoblast) cell integration into endothelial tubular structures by 24.1±3.7% pintegration of trophoblast into endothelial tubular structures in the presence

Hydrogen Production by a Hyperthermophilic Membrane-Bound Hydrogenase in Soluble Nanolipoprotein Particles

Energy Technology Data Exchange (ETDEWEB)

Baker, S E; Hopkins, R C; Blanchette, C; Walsworth, V; Sumbad, R; Fischer, N; Kuhn, E; Coleman, M; Chromy, B; Letant, S; Hoeprich, P; Adams, M W; Henderson, P T

2008-10-22

Hydrogenases constitute a promising class of enzymes for ex vivo hydrogen production. Implementation of such applications is currently hindered by oxygen sensitivity and, in the case of membrane-bound hydrogenases (MBH), poor water solubility. Nanolipoprotein particles (NLPs), formed from apolipoproteins and phospholipids, offer a novel means to incorporate MBH into in a well-defined water-soluble matrix that maintains the enzymatic activity and is amenable to incorporation into more complex architectures. We report the synthesis, hydrogen-evolving activity and physical characterization of the first MBH-NLP assembly. This may ultimately lead to the development of biomimetic hydrogen production devices.

Influence of apolipoprotein-E gene on lipid profile, physical activity and body fat relationship

Directory of Open Access Journals (Sweden)

Thales Boaventura Rachid Nascimento

2012-03-01

Full Text Available Physical activity and body fat modify lipemia, and this effect seems to be influenced by apolipoprotein-E (APOE gene polymorphism. Thus, the purpose of this article was to review main results of studies that have analyzed the relation of APOE gene with physical activity and body fat on triglycerides, total cholesterol and low (LDL and high density lipoprotein (HDL concentrations. The Scientific Electronic Library Online – SciELO, Web of Science and PubMed database were used to locate the articles. The keywords used in combination were: apoe genotype, apolipoprotein-E polymorphism, physical exercise, physical activity, aerobic exercise, body fat and obesity. Originals scientific investigations performed with humans were included, and excluded those ones which involved samples with diseases, except obesity and/or lipemic disorders. It was observed a trend, that ε2 allele carriers are the ones with the greater improvements on lipemia from physical exercise. In addition, the body fat impact on the elevation of triglycerides and LDL are stronger in carriers of the ε2 and ε4 allele, respectively. Considering the small number of originals scientific investigations and their divergent results, reliable inferences can not be made about the APOE gene polymorphism influences on physical activity and body fat effect on lipemia. Thus, further studies with others populations and more volunteers for allele, as well as others exercise modalities and intensities, are necessary.

The apolipoprotein m-sphingosine-1-phosphate axis

DEFF Research Database (Denmark)

Arkensteijn, Bas W C; Berbée, Jimmy F P; Rensen, Patrick C N

2013-01-01

Apolipoprotein M (apoM) is a plasma apolipoprotein that mainly associates with high-density lipoproteins. Hence, most studies on apoM so far have investigated its effect on and association with lipid metabolism and atherosclerosis. The insight into apoM biology recently took a major turn. Apo...

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

2009-01-01

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...

In the absence of endogenous mouse apolipoprotein E, apolipoprotein E*2(Arg-158 → Cys) transgenic mice develop more severe hyperlipoproteinemia than apolipoprotein E*3-Leiden transgenic mice

NARCIS (Netherlands)

Vlijmen, B.J.M. van; Dijk, K.W. van; Hof, H.B. van 't; Gorp, P.J.J. van; Zee, A. van der; Boom, H. van der; Breuer, M.L.; Hofker, M.H.; Havekesf, L.M.

1996-01-01

Apolipoprotein E*2(Arg-155 → Cys) (APOE*2) transgenic mice were generated and compared to the previously generated apolipoprotein E*3- Leiden (APOE*3-Leiden) transgenic mice to study the variable expression of hyperlipoproteinemia associated with these two APOE variants. In the presence of the

IMB2026791, a Xanthone, Stimulates Cholesterol Efflux by Increasing the Binding of Apolipoprotein A-I to ATP-Binding Cassette Transporter A1

Directory of Open Access Journals (Sweden)

Zijian Xie

2012-03-01

Full Text Available It is known that the ATP-binding cassette transporter A1 (ABCA1 plays a major role in cholesterol homeostasis and high density lipoprotein (HDL metabolism. Several laboratories have demonstrated that ABCA1 binding to lipid-poor apolipoprotein A-I (apoA-I will mediate the assembly of nascent HDL and cellular cholesterol efflux, which suggests a possible receptor-ligand interaction between ABCA1 and apoA-I. In this study, a cell-based-ELISA-like high-throughput screening (HTS method was developed to identify the synthetic and natural compounds that can regulate binding activity of ABCA1 to apoA-I. The cell-based-ELISA-like high-throughput screen was conducted in a 96-well format using Chinese hamster ovary (CHO cells stably transfected with ABCA1 pIRE2-EGFP (Enhanced Green Fluorecence Protein expression vector and the known ABCA1 inhibitor glibenclamide as the antagonist control. From 2,600 compounds, a xanthone compound (IMB 2026791 was selected using this HTS assay, and it was proved as an apoA-I binding agonist to ABCA1 by a flow cytometry assay and western blot analysis. The [3H] cholesterol efflux assay of IMB2026791 treated ABCA1-CHO cells and PMA induced THP-1 macrophages (human acute monocytic leukemia cell further confirmed the compound as an accelerator of cholesterol efflux in a dose-dependent manner with an EC50 of 25.23 μM.

Apolipoprotein E in umbilical cord blood plasma

International Nuclear Information System (INIS)

Forte, T.M.; Davis, P.A.; Blum, C.B.

1983-01-01

Adolipoprotein E (apo E), with a molecular weight of approximately 37,000 daltons, is a minor apolipoprotein constituent in adult plasma lipoproteins. This apolipoprotein, like apolipoprotein B, is a ligand recognized by specific lipoprotein receptor sites (B-E receptors) on cell surfaces. We have recently shown that a pronounced apo E band appears in umbilical cord blood low-density (LDL) lipoproteins and also in high density (HDL) lipoproteins. Densitometric scans of Coomassie blue G-250 stained polyacrylamide gels suggested that apo E was probably elevated in cord blood lipoproteins. To pursue this suggestion, apo E in cord blood was quantitated by radioimmunoassay and correlated with cord blood lipid levels. In addition, apo E levels in 20 normal adult volunteers were also examined

Molecular basis of the apolipoprotein H (beta 2-glycoprotein I) protein polymorphism

DEFF Research Database (Denmark)

Sanghera, Dharambir K; Kristensen, Torsten; Hamman, Richard F

1997-01-01

Apolipoprotein H (apoH, protein; APOH, gene) is considered to be an essential cofactor for the binding of certain antiphospholipid autoantibodies to anionic phospholipids. APOH exhibits a genetically determined structural polymorphism due to the presence of three common alleles (APOH*1, APOH*2...... was observed sporadically in blacks (0.008), it was present at a polymorphic frequency in Hispanics (0.027) and non-Hispanic whites (0.059). The identification of the molecular basis of the APOH protein polymorphism will help to elucidate the structural – functional relationship of apoH in the production...

Impact of Serum Apolipoprotein A-I on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer: a Propensity Score-Matched Analysis

Directory of Open Access Journals (Sweden)

Qi Quan

2017-04-01

Full Text Available PURPOSE: We aimed to investigate the role of apolipoprotein A-I (ApoA-I as a predictor of prognosis and treatment efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC treated with first-line chemotherapy with or without bevacizumab. METHODS: We conducted a retrospective study on consecutive patients who were diagnosed with mCRC at Sun Yat-sen University Cancer Center. According to their pretreatment ApoA-I level, patients were divided into low– and high–ApoA-I groups. Propensity score-matched method was performed to balance baseline characteristics between two groups. Based on whether they accepted bevacizumab as a first-line therapy, patients were further divided into the chemo + bevacizumab group and the chemo group. Overall survival (OS and progression-free survival (PFS were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: The optimal cutoff value for the ApoA-I level was determined to be 1.105 g/l. In the propensity-matched cohort of 508 patients, low ApoA-I was significantly associated with inferior OS (P < .001 and PFS (P < .001 than high ApoA-I. Multivariate analysis showed that ApoA-I level was an independent prognostic maker of OS (P < .001 and PFS (P = .001. PFS (P < .001 in either the high– or low–ApoA-I groups could be extended significantly after the administration of bevacizumab, and patients with a high ApoA-I level also had a better OS in the chemo + bevacizumab group than the chemo group (P = .049. CONCLUSIONS: Patients with a low ApoA-I level have poor prognoses, and they did not display an OS benefit from bevacizumab.

Impact of corpulence parameters and haemoglobin A1c on metabolic control in type 2 diabetic patients: comparison of apolipoprotein B/A-I ratio with fasting and postprandial conventional lipid ratios

Directory of Open Access Journals (Sweden)

Mustapha Diaf

2015-05-01

Full Text Available Background and objective: The incidence of diabetes co-morbidities could probably be better assessed by studying its associations with major corpulence parameters and glycaemic control indicators. We assessed the utility of body mass index (BMI, waist circumference (WC, and glycosylated haemoglobin (HbA1c levels in metabolic control for type 2 diabetic patients. Methods: Fasting and postprandial blood samples were collected from 238 type 2 diabetic patients aged 57.4±11.9 years. The sera were analysed for glucose, HbA1c, total cholesterol (TC, triglycerides (TG, high-density lipoprotein cholesterol (HDL-c, low-density lipoprotein cholesterol (LDL-c, and apolipoproteins (apoA-I and apoB. Ratios of lipids and apolipoproteins were calculated and their associations with BMI, WC, and HbA1c levels were analysed. Results: Our investigation showed increases in most fasting and postprandial lipid parameters according to BMI and WC. In men, postprandial HDL-c and TG levels were significantly higher (p<0.05 in overweight and obese patients, respectively, as well as in patients with abdominal obesity. Contrariwise, postprandial TC levels were significantly higher (p<0.01 in overweight and abdominal obese women. However, elevations of apoA-I and apoB levels were according to BMI and WC in both genders. There was a strong influence of BMI, WC, and HbA1c levels on the apoB/apoA-I ratio compared to traditional fasting and postprandial lipid ratios in both men and women. The apoB/apoA-I ratio was more correlated with postprandial TC/HDL and LDL-c/HDL-c ratios in men and with postprandial TG/HDL-c in women. Conclusion: The apoB/apoA-I ratio is helpful in assessing metabolic risk caused by overall obesity, abdominal obesity and impaired glycaemia in type 2 diabetic patients.

Metabolism of apolipoproteins C-II, C-III, and B in hypertriglyceridemic men. Changes after heparin-induced lipolysis

International Nuclear Information System (INIS)

Huff, M.W.; Breckenridge, W.C.; Strong, W.L.; Wolfe, B.M.

1988-01-01

The C apolipoproteins are normally transferred to high density lipoproteins (HDL) after lipolysis of very low density lipoprotein (VLDL) triglyceride. In previous studies, a loss of plasma C apolipoproteins was documented after heparin-induced lipolysis in hypertriglyceridemic subjects. The present studies were designed to determine if this decline in plasma C apolipoproteins was due to their clearance with VLDL remnants. Five Type IV hypertriglyceridemic and two normal subjects were injected with 125I-VLDL and 131I-low density lipoproteins (LDL) to document kinetically an excess of VLDL apolipoprotein (apo) B flux relative to LDL apo B flux in the Type IV subjects. A mean of 46% VLDL apo B was cleared from the circulation, without conversion to intermediate density lipoprotein (IDL) or LDL. Heparin was then infused (9000 IU over 4 hours) to generate an excess of VLDL remnants that were not converted to IDL or LDL. VLDL triglyceride, apo B, and apo C concentrations fell at a similar rate. VLDL apo B declined by 42% (p less than 0.01). However, no increases were observed in IDL or LDL apo B in the Type IV subjects. This resulted in a 14% (p less than 0.01) decline in plasma apo B concentrations, indicating a clearance of VLDL remnants. VLDL apo C-II and C-III concentrations fell by 42% (p less than 0.025) and 52% (p less than 0.01), respectively. During the first 2.5 hours of infusion, they were almost quantitatively recovered in HDL. Thereafter, the C apolipoproteins declined in HDL during which time VLDL apo C concentrations continued to decline

Apolipoprotein A-IV interacts synergistically with melanocortins to reduce food intake.

Science.gov (United States)

Gotoh, Koro; Liu, Min; Benoit, Stephen C; Clegg, Deborah J; Davidson, W Sean; D'Alessio, David; Seeley, Randy J; Tso, Patrick; Woods, Stephen C

2006-01-01

Apolipoprotein (apo) A-IV is an anorexigenic gastrointestinal peptide that is also synthesized in the hypothalamus. The goal of these experiments was to determine whether apo A-IV interacts with the central melanocortin (MC) system in the control of feeding. The third ventricular (i3vt) administration of a subthreshold dose of apo A-IV (0.5 microg) potentiated i3vt MC-induced (metallothionein-II, 0.03 nmol) suppression of 30-min feeding in Long-Evans rats. A subthreshold dose of the MC antagonist (SHU9119, 0.1 nmol, i3vt) completely attenuated the anorectic effect of i3vt apo A-IV (1.5 microg). The i3vt apo A-IV significantly elevated the expression of c-Fos in neurons of the paraventricular nucleus of the hypothalamus, but not in the arcuate nucleus or median eminence. In addition, c-Fos expression was not colocalized with proopiomelanocortin-positive neurons. These data support a synergistic interaction between apo A-IV and melanocortins that reduces food intake by acting downstream of the arcuate.

Major lipids, apolipoproteins, and risk of vascular disease

DEFF Research Database (Denmark)

Collaboration, Emerging Risk Factors; Di Angelantonio, Emanuele; Sarwar, Nadeem

2009-01-01

CONTEXT: Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified. OBJECTIVE: To assess major lipids and apolipoproteins in vascular risk. DESIGN, SETTING, AND PARTICIPANTS: Individual records were supplied on 302,430 people without...

Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100

International Nuclear Information System (INIS)

Soria, L.F.; Ludwig, E.H.; Clarke, H.R.G.; McCarthy, B.J.; Vega, G.L.; Grundy, S.M.

1989-01-01

Familial defective apolipoprotein (apo) B-100 is a genetic disease that leads to hypercholesterolemia and to an increased serum concentration of low density lipoproteins that bind defectively to the apoB,E(LDL) receptor. The disorder appears to result from a mutation in the gene for apoB-100. Extensive sequence analysis of the two alleles of one subject heterozygous for the disorder has revealed a previously unreported mutation in the codon for amino acid 3500 that results in the substitution of glutamine for arginine. This same mutant allele occurs in six other, unrelated subjects and in eight affected relatives in two of these families. A partial haplotype of this mutant apoB-100 allele was constructed by sequence analysis and restriction enzyme digestion at positions where variations in the apoB-100 are known to occur. This haplotype is the same in three probands and four affected members of one family and lacks a polymorphic Xba I site whose presence has been correlated with high cholesterol levels. Thus, it appears that the mutation in the codon for amino acid 3500 (CGG → CAG), a CG mutational hot spot, defines a minor apoB-100 allele associated with defective low density lipoproteins and hypercholesterolemia

The signal peptide anchors apolipoprotein M in plasma lipoproteins and prevents rapid clearance of apolipoprotein M from plasma

DEFF Research Database (Denmark)

Christoffersen, Christina; Ahnström, Josefin; Axler, Olof

2008-01-01

Lipoproteins consist of lipids solubilized by apolipoproteins. The lipid-binding structural motifs of apolipoproteins include amphipathic alpha-helixes and beta-sheets. Plasma apolipoprotein (apo) M lacks an external amphipathic motif but, nevertheless, is exclusively associated with lipoproteins...... (mainly high density lipoprotein). Uniquely, however, apoM is secreted to plasma without cleavage of its hydrophobic NH(2)-terminal signal peptide. To test whether the signal peptide serves as a lipoprotein anchor for apoM in plasma, we generated mice expressing a mutated apoM(Q22A) cDNA in the liver (apoM......(Q22A)-Tg mice (transgenic mice)) and compared them with mice expressing wild-type human apoM (apoM-Tg mice). The substitution of the amino acid glutamine 22 with alanine in apoM(Q22A) results in secretion of human apoM without a signal peptide. The human apoM mRNA level in liver and the amount...

Rosuvastatin does not affect human apolipoprotein A-I expression in genetically modified mice: a clue to the disputed effect of statins on HDL.

Science.gov (United States)

Marchesi, Marta; Parolini, Cinzia; Caligari, Silvia; Gilio, Donatella; Manzini, Stefano; Busnelli, Marco; Cinquanta, Paola; Camera, Marina; Brambilla, Marta; Sirtori, Cesare R; Chiesa, Giulia

2011-11-01

Besides a significant reduction of low-density lipoprotein (LDL) cholesterol, statins moderately increase high-density lipoprotein (HDL) levels. In vitro studies have indicated that this effect may be the result of an increased expression of apolipoprotein (apo)A-I, the main protein component of HDL. The aim of the present study was to investigate in vivo the effect of rosuvastatin on apoA-I expression and secretion in a transgenic mouse model for human apoA-I. Human apoA-I transgenic mice were treated for 28 days with 5, 10 or 20 mg·kg(-1) ·day(-1) of rosuvastatin, the most effective statin in raising HDL levels. Possible changes of apoA-I expression by treatment were investigated by quantitative real-time RT-PCR on RNA extracted from mouse livers. The human apoA-I secretion rate was determined in primary hepatocytes isolated from transgenic mice from each group after treatment. Rosuvastatin treatment with 5 and 10 mg·kg(-1) ·day(-1) did not affect apoA-I plasma levels, whereas a significant decrease was observed in mice treated with 20 mg·kg(-1) ·day(-1) of rosuvastatin (-16%, P < 0.01). Neither relative hepatic mRNA concentrations of apoA-I nor apoA-I secretion rates from primary hepatocytes were influenced by rosuvastatin treatment at each tested dose. In human apoA-I transgenic mice, rosuvastatin treatment does not increase either apoA-I transcription and hepatic secretion, or apoA-I plasma levels. These results support the hypothesis that other mechanisms may account for the observed HDL increase induced by statin therapy in humans. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

A study of serum lipid profile and serum apolipoproteins A1 and B in Indian male violent criminal offenders.

Science.gov (United States)

Chakrabarti, Nandini; Sinha, V K

2006-01-01

High cholesterol has been advanced as the most important factor in the development of coronary artery disease. Most panels have recommended population-wide dietary restrictions, yet a body of evolving data yields evidence of the hazards of low cholesterol, including links to aggression and hostility. The aim of this study was to compare the serum lipid profile and serum apolipoproteins A1 and B of men with a violent criminal record and men with no criminal history. Fasting blood samples were collected from 30 men with a known history of violent crime and 30 men with no criminal record. Serum lipid profile and serum apolipoproteins A1 and B were measured in each sample, and compared between the two groups. The group with the violent criminal record showed significantly lower total cholesterol, lower LDL cholesterol, higher apolipoprotein A1 and lower apolipoprotein B compared with the control group. Lower total cholesterol, lower LDL cholesterol, higher apolipoprotein A1 and lower apolipoprotein B could predispose to violence. Future research might explore the possibility that diets offered in prison could affect relevant pathways in lipid metabolism. Copyright (c) 2006 John Wiley & Sons, Ltd.

Influences of apolipoprotein E on soluble and heparin-immobilized hepatic lipase

International Nuclear Information System (INIS)

Landis, B.A.; Rotolo, F.S.; Meyers, W.C.; Clark, A.B.; Quarfordt, S.H.

1987-01-01

The effect of human apolipoprotein E (apoE), either alone or in combination with apoC, on the lipolysis of a radiolabeled triglyceride emulsion was studied with hepatic lipase in solution and immobilized on heparin-Sepharose. The soluble hepatic lipase was inhibited, whereas the heparin-immobilized lipase was stimulated by apoE. This stimulation was attenuated by combining apoE with either apoC-II or C-III. The heparin-immobilized lipase demonstrated much less lipolysis of the zwitterionic phosphatidylcholine-stabilized triglyceride emulsion than did the soluble enzyme. This difference was less when the emulsion was stabilized by a nonionic detergent. apoE inhibited lipase activity when assayed under conditions (0.4 M NaCl) of bound enzyme and unbound substrate. Increasing the emulsion apoE content beyond optimum inhibited lipolysis by the immobilized enzyme. Kinetic analysis of phosphatidylcholine-stabilized triglyceride emulsions revealed a significant decrease in immobilized enzyme K/sub m/ and an increase in V/sub max/ when the emulsion was supplemented with apoE. Distributing the immobilized lipase in clustered aggregates produced more lipolysis than when the same enzyme content was uniformly bound

Amphotericin B induced interdigitation of apolipoprotein stabilized nanodisk bilayers

Energy Technology Data Exchange (ETDEWEB)

Nguyen, T; Weers, P M; Sulchek, T; Hoeprich, P D; Ryan, R O

2006-12-07

Amphotericin B nanodisks (AMB-ND) are ternary complexes of AMB, phospholipid (PL) and apolipoprotein organized as discrete nanometer scale disk-shaped bilayers. In gel filtration chromatography experiments, empty ND lacking AMB elute as a single population of particles with a molecular weight in the range of 200 kDa. AMB-ND formulated at a 4:1 PL:AMB weight ratio, separated into two peaks. Peak 1 eluted at the position of control ND lacking AMB while the second peak, containing all of the AMB present in the original sample, eluted in the void volume. When ND prepared with increased AMB (1:1 phospholipid:AMB molar ratio) were subjected to gel filtration chromatography, an increased proportion of phospholipid and apolipoprotein were recovered in the void volume with the AMB. Prior to gel filtration the AMB-ND sample could be passed through a 0.22 {micro}m filter without loss of AMB while the voided material was lost. Native gel electrophoresis studies corroborated the gel permeation chromatography data. Far UV circular dichroism analyses revealed that apoA-I associated with AMB-ND denatures at a lower guanidine HCl concentration than apoA-I associated with ND lacking AMB. Atomic force microscopy revealed that AMB induces compression of the ND bilayer thickness consistent with bilayer interdigitation, a phenomenon that is likely related to the ability of AMB to induce pore formation in susceptible membranes.

Apolipoprotein M mediates sphingosine-1-phosphate efflux from erythrocytes

DEFF Research Database (Denmark)

Christensen, Pernille M.; Bosteen, Markus H.; Hajny, Stefan

2017-01-01

Sphingosine-1-phosphate (S1P) is a bioactive lipid implicated in e.g. angiogenesis, lymphocyte trafficking, and endothelial barrier function. Erythrocytes are a main source of plasma S1P together with platelets and endothelial cells. Apolipoprotein M (apoM) in HDL carries 70% of plasma S1P, whereas...... 30% is carried by albumin. The current aim was to investigate the role of apoM in export of S1P from human erythrocytes. Erythrocytes exported S1P more efficiently to HDL than to albumin, particularly when apoM was present in HDL. In contrast, export of sphingosine to HDL was unaffected...... by the presence of apoM. The specific ability of apoM to promote export of S1P was independent of apoM being bound in HDL particles. Treatment with MK-571, an inhibitor of the ABCC1 transporter, effectively reduced export of S1P from human erythrocytes to apoM, whereas the export was unaffected by inhibitors...

Circulating Apolipoprotein A1, Haptoglobin and Α2 Macroglobulin ...

African Journals Online (AJOL)

α2-MG), Apolipoprotein A1 (Apo-1) and Haptoglobin (HP) as non-invasive index of the presence of cirrhosis in chronic hepatitis C patients in relation to the histopathological findings. Subjects and Methods: The study was carried out on 20 ...

Apolipoprotein A-V is present in bile and its secretion increases with lipid absorption in Sprague-Dawley rats.

Science.gov (United States)

Zhang, Linda S; Sato, Hirokazu; Yang, Qing; Ryan, Robert O; Wang, David Q-H; Howles, Philip N; Tso, Patrick

2015-12-01

Apolipoprotein (apo) A-V is a protein synthesized only in the liver that dramatically modulates plasma triglyceride levels. Recent studies suggest a novel role for hepatic apoA-V in regulating the absorption of dietary triglycerides, but its mode of action on the gut remains unknown. The aim of this study was to test for apoA-V in bile and to determine whether its secretion is regulated by dietary lipids. After an overnight recovery, adult male Sprague-Dawley bile fistula rats indeed secreted apoA-V into bile at a constant rate under fasting conditions. An intraduodenal bolus of intralipid (n = 12) increased the biliary secretion of apoA-V but not of other apolipoproteins, such as A-I, A-IV, B, and E. The lipid-induced increase of biliary apoA-V was abolished under conditions of poor lymphatic lipid transport, suggesting that the stimulation is regulated by the magnitude of lipids associated with chylomicrons transported into lymph. We also studied the secretion of apoA-V into bile immediately following bile duct cannulation. Biliary apoA-V increased over time (∼6-fold increase at hour 16, n = 8) but the secretions of other apolipoproteins remained constant. Replenishing luminal phosphatidylcholine and taurocholate (n = 9) only enhanced apoA-V secretion in bile, suggesting that the increase was not due to depletion of phospholipids or bile salts. This is the first study to demonstrate that apoA-V is secreted into bile, introducing a potential route of delivery of hepatic apoA-V to the gut lumen. Our study also reveals the uniqueness of apoA-V secretion into bile that is regulated by mechanisms different from other apolipoproteins. Copyright © 2015 the American Physiological Society.

Binding of recombinant apolipoprotein(a) to extracellular matrix proteins

NARCIS (Netherlands)

van der Hoek, Y. Y.; Sangrar, W.; Côté, G. P.; Kastelein, J. J.; Koschinsky, M. L.

1994-01-01

Elevated levels of lipoprotein(a), which consists of apolipoprotein(a) [apo(a)] covalently linked to a low-density lipoprotein-like moiety, is an independent risk factor for the development of atherosclerosis. We show that a recombinant form of apo(a) [r-apo(a)] binds strongly to fibronectin and

Apolipoprotein A5 in health and disease

Czech Academy of Sciences Publication Activity Database

Hubáček, J. A.; Adámková, V.; Vrablík, M.; Kadlecová, Michaela; Zicha, Josef; Kuneš, Jaroslav; Piťha, J.; Suchánek, P.; Poledne, R.

2009-01-01

Roč. 58, Suppl.2 (2009), S101-S109 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Grant - others:IKEM(CZ) 00023001; GA MŠk(CZ) MEB060808; GA MZd(CZ) NR8895; GAMZd(CZ) NR9393 Institutional research plan: CEZ:AV0Z50110509 Keywords : apolipoprotein A5 * plasma triglycerides * myocardial infarction Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.430, year: 2009

Plasma lipoproteins as mediators of the oxidative stress induced by UV light in human skin: a review of biochemical and biophysical studies on mechanisms of apolipoprotein alteration, lipid peroxidation, and associated skin cell responses.

Science.gov (United States)

Filipe, Paulo; Morlière, Patrice; Silva, João N; Mazière, Jean-Claude; Patterson, Larry K; Freitas, João P; Santus, R

2013-01-01

There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL) and low-density lipoprotein (LDL) as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces (•)Trp and (•)O2 (-) radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO(•)) by α -tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α -tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α -tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α -tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.

Plasma Lipoproteins as Mediators of the Oxidative Stress Induced by UV Light in Human Skin: A Review of Biochemical and Biophysical Studies on Mechanisms of Apolipoprotein Alteration, Lipid Peroxidation, and Associated Skin Cell Responses

Directory of Open Access Journals (Sweden)

Paulo Filipe

2013-01-01

Full Text Available There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL and low-density lipoprotein (LDL as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces •Trp and O2•- radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO• by α-tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α-tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α-tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α-tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.

Reversal of hypercholesterolemia in apolipoprotein E2 and apolipoprotein E3-Leiden transgenic mice by adenovirus-mediated gene transfer of the VLDL receptor

NARCIS (Netherlands)

Dijk, K.W. van; Vlijmen, B.J.M. van; Zee, A. van der; Hof, B. van 't; Boom, H. van der; Kobayashi, K.; Chan, L.; Havekes, L.M.; Hofker, M.H.

1998-01-01

We have investigated the interaction of apolipoprotein E2(Arg158- Cys) (apoE2) and apolipoprotein E3Leiden (apoE3-Leiden) with the very low density lipoprotein (VLDL) receptor in vivo and in vitro to define the possible role of this receptor in lipoprotein metabolism and atherosclerosis. The in vivo

Genetic association of apolipoprotein E with age-related macular degeneration

NARCIS (Netherlands)

M. Kliffen (Mike); C.M. van Duijn (Cornelia); M. Cruts (Marc); D.E. Grobbee (Diederick); P.T.V.M. de Jong (Paulus); C.C.W. Klaver (Caroline); C. van Broeckhoven (Christine); A. Hofman (Albert)

1998-01-01

textabstractAge-related macular degeneration (AMD) is the most common geriatric eye disorder leading to blindness and is characterized by degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein of the CNS and an

[Apolipoprotein e polymorphism and cognitive function change of the elderly in a rural area, Korea].

Science.gov (United States)

Kim, Sang Kyu; Hwang, Tae Yoon; Lee, Kyeong Soo; Kang, Pock Soo; Cho, Hee Soon; Bae, Young Kyung

2009-07-01

The aim of this study is to examine the cognitive function change related to aging, the incidence of cognitive impairment, and the association between apolipoprotein E polymorphism and cognitive impairment through a follow-up of the elderly with normal cognitive ability at baseline. Two hundred and fifteen subjects aged 65 and over were surveyed in February, 1998 (baseline survey), and their cognitive function was assessed again in 2003 (1st follow-up) and the once again in 2006 (2nd follow-up). Ninety one subjects completed all surveys up through the 2nd follow-up and their cognitive function scores using MMSE-K (Korean Version of the Mini-Mental State Examination) and the distribution of apolipoprotein E allele were analyzed. The cognitive function scores decreased with aging and the difference between baseline and the 2nd follow-up scores of the study increased with the age group. The incidence rate of cognitive impairment through an 8-year follow-up was 38.5% and higher in older age groups. Age was the only significant factor for incidence of cognitive impairment, but there was no significant association between apolipoprotein E genotype and incidence of cognitive impairment. The cognition of the elderly decreased with aging and the association of apolipoprotein E genotype with incidence of cognitive impairment was not significant in this study. To confirm the association between apolipoprotein E polymorphism and incidence of cognitive impairment further studies will be needed.

DMPD: Regulation of endogenous apolipoprotein E secretion by macrophages. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18388328 Regulation of endogenous apolipoprotein E secretion by macrophages. Kockx ...svg) (.html) (.csml) Show Regulation of endogenous apolipoprotein E secretion by macrophages. PubmedID 18388...328 Title Regulation of endogenous apolipoprotein E secretion by macrophages. Aut

The Apolipoprotein C-I Content of Very-Low-Density Lipoproteins Is Associated with Fasting Triglycerides, Postprandial Lipemia, and Carotid Atherosclerosis

Directory of Open Access Journals (Sweden)

John-Bjarne Hansen

2011-01-01

Full Text Available Background. Experimental studies in animals suggest that apolipoprotein (apo C-I is an important regulator of triglycerides in fasting and postprandial conditions and associated with carotid atherosclerosis. Methods. A cross-sectional study was conducted with 81 subjects, aged 56–80 years recruited from a population health survey. The participants underwent a fat tolerance test (1 g fat per Kg body weight and carotid atherosclerosis was determined by ultrasound examination. VLDL particles, Sf 20–400, were isolated and their lipid composition and apoC-I content determined. Results. The carotid plaque area increased linearly with the number of apoC-I molecules per VLDL particles (P=0.048 under fasting conditions. Fasting triglycerides increased across tertiles of apoC-I per VLDL particle in analyses adjusted for apoC-II and -C-III, apoE genotype and traditional cardiovascular risk factors (P=0.011. The relation between apoC-I in VLDL and serum triglycerides was conveyed by triglyceride enrichment of VLDL particles (P for trend <0.001. The amount of apoC-I molecules per VLDL was correlated with the total (r=0.41, P<0.0001 and incremental (r=0.35, P<0.001 area under the postprandial triglyceride curve. Conclusions. Our findings support the concept that the content of apoC-I per VLDL particle is an important regulator of triglyceride metabolism in the fasting and postprandial state and associated with carotid athrosclerosis.

Postmenopausal hypertension, abdominal obesity, apolipoprotein and insulin resistance.

Science.gov (United States)

Ben Ali, Samir; Belfki-Benali, Hanen; Ahmed, Decy Ben; Haddad, Najet; Jmal, Awatef; Abdennebi, Monia; Romdhane, Habiba Ben

This study aimed to evaluate the association of abdominal obesity, apolipoprotein and insulin resistance (IR) with the risk of hypertension in postmenopausal women. We analyzed a total of 242 women aged between 35 and 70 years. Blood pressure (BP), anthropometric indices, lipid profile, fasting glucose, insulin, C-reactive protein (CRP) and apolipoprotein concentrations were measured. Homeostasis model assessment (HOMA) was used to assess IR. Hypertension was defined as a systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg or current treatment with antihypertensive drugs. Women with hypertension showed significantly higher mean values of age, SBP and DBP, waist circumference (WC), fasting plasma glucose (FPG), insulin, HOMAIR and the apolipoprotein B (apoB). When analyses were done according to the menopausal status, higher prevalence of hypertension was observed in postmenopausal women (72.8% vs. 26.0%, p menopause (p = 0.008) were significantly associated with higher risk for hypertension. These results suggest that changes in WC, apoB and IR accompanying menopause lead to a greater prevalence of hypertension in postmenopausal women.

Increased concentration of clusterin/apolipoprotein J (apoJ) in hyperlipemic serum is paradoxically associated with decreased apoJ content in lipoproteins.

Science.gov (United States)

Rull, Anna; Martínez-Bujidos, Maria; Pérez-Cuellar, Montserrat; Pérez, Antonio; Ordóñez-Llanos, Jordi; Sánchez-Quesada, José Luis

2015-08-01

Clusterin/apolipoprotein J (apoJ) circulates in blood in part associated to lipoproteins or in unbound form. When bound to HDL, apoJ is antiatherogenic by inhibiting endothelial cell apoptosis; thus, any factor modifying apoJ association to HDL would decrease its antiatherogenic function. However, the exact distribution of apoJ in each lipoprotein fraction, or in lipoprotein-non bound form has not been specifically investigated either in normolipemia or in dyslipemia. Basic lipid profile and apoJ concentration were determined in sera from 70 subjects, including a wide range of cholesterol and triglyceride concentrations. Lipoproteins were isolated by ultracentrifugation and their lipid and apolipoprotein composition was assessed. In the overall population, serum apoJ positively associated with cholesterol, triglyceride and VLDL-C concentrations, and HDL-C and triglyceride were independent predictors of increased apoJ concentration. Approximately, 20.5% of circulating apoJ was associated with lipoproteins (18.5% HDL, 0.9% LDL and 1.1% VLDL) and 79.5% was not bound to lipoproteins. Serum apoJ concentration was higher in hypercholesterolemic (HC), hypertriglyceridemic (HTG) and combined hyperlipidemic (CHL) sera compared to normolipemic (NL) sera (HC, 98.15 ± 33.6 mg/L; HTG, 103.3 ± 36.8 mg/L; CHL, 131.7 ± 26.8 mg/L; NL, 66.7 ± 33.8 mg/L; P lipoproteins in the NL group whereas this proportion rounded 15% in hyperlipidemic subjects. Our findings indicate that hyperlipidemia increases the concentration of apoJ in serum but, in turn, the content of lipoprotein-associated apoJ decreases. The redistribution of apoJ in hyperlipidemia could compromise the antiatherogenic properties of HDL. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Apolipoprotein a5 and hypertriglyceridemia in prague hypertriglyceridemic rats

Czech Academy of Sciences Publication Activity Database

Kadlecová, Michaela; Hojná, Silvie; Bohuslavová, R.; Hubáček, J. A.; Zicha, Josef; Kuneš, Jaroslav

2006-01-01

Roč. 55, č. 4 (2006), s. 373-379 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/03/0769 Institutional research plan: CEZ:AV0Z50110509 Keywords : metabolic syndrome * apolipoprotein A5 * rat Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

ApolipoproteinA1-75 G/A (M1- polymorphism and Lipoprotein(a; Anti- vs. Pro-Atherogenic properties

Directory of Open Access Journals (Sweden)

Ranganath L

2007-08-01

Full Text Available Abstract Background ApolipoproteinA1(apoA1 is the major apoprotein constituent of high-density-lipoprotein(HDL. The relationship of apoA1 -75 bp(M1- allele polymorphism with lipoprotein phenotype and cardiovascular diseae (CVD remain unclear. Overnight fasting blood samples were collected from a cohort of high-risk Omani population, 90 non-diabetic subjects and 149 type 2 diabetes mellitus (T2DM subjects for genotype and phenotype studies. Results The M1+ and M1- alleles frequencies were 0.808 and 0.192 for M1+ and M1-, respectively, comparable to the frequency of apoA1 (M1+ and M1- amongst a healthy Omani population, 0.788 and 0.212, respectively. The frequencies of the hetero- and homozygous subjects for the MspI polymorphism at -75 (M1- of the apoA1 gene were in Hardy-Weinberg equilibrium. The mean Lp(a concentration was significantly higher(P = 0.02 in subjects carrying M1- allele compared to M1+ allele of the APOA1 gene with an odd ratio of 2.3(95% CI, 1.13–14.3, irrespective of gender and the diabetic status. Conclusion ApolipoproteinA1-75 G/A (M1- polymorphism is relatively common and is positively associated with Lp(a and therefore, may confer a potential risk for cardiovascular disease (CVD.

Apolipoprotein M affecting lipid metabolism or just catching a ride with lipoproteins in the circulation?

DEFF Research Database (Denmark)

Dahlbäck, B; Nielsen, Lars Bo

2009-01-01

Apolipoprotein M (apoM) is a novel apolipoprotein found mainly in high-density lipoproteins (HDL). Its function is yet to be defined. ApoM (25 kDa) has a typical lipocalin ss-barrel fold and a hydrophobic pocket. Retinoids bind apoM but with low affinity and may not be the natural ligands. ApoM r......; possible mechanisms include increased formation of pre-ss HDL, enhanced cholesterol mobilization from foam cells, and increased antioxidant properties....

In search of new structural states of exchangeable apolipoproteins

International Nuclear Information System (INIS)

Xicohtencatl-Cortes, J.; Castillo, R.; Mas-Oliva, J.

2004-01-01

Based upon state of the art biophysical experimentation, this article focuses on the different structural arrangements exchangeable apolipoproteins achieve when placed on Langmuir monolayers and subjected to changes in lateral pressure. We have studied the monolayers of apolipoproteins CI, CIII, AI, AII, and E that show as secondary structure a high percentage of amphipathic α-helix. This has been achieved employing techniques such as Brewster angle microscopy, synchrotron X-ray diffraction, and surface pressure measurements. In addition, the lateral order of protein arrays has been also studied by atomic force microscopy. These monolayers show that a phase transition from a two-dimensional disorder fluid to an ordered state is detected at relatively high lateral pressure, where unusual one-dimensional solid phases are discovered. While several helices that conform the apolipoprotein are confined to the interface, others are uniformly tilted toward the hydrophobic air or the phospholipid fatty acid chains. Our results suggest that a similar ordering might also occur when these apolipoproteins are attached to a lipoprotein particle such as a high density lipoprotein (HDL) particle. Therefore, changes from a nascent or discoidal HDL to a mature spherical HDL might in parallel involve structural changes as those described in our Langmuir interfaces. Current experimentation is being carried out in order to elucidate if the structural states already found are related to the efficiency of lipid transfer between lipoprotein particles or lipoproteins and the plasma membrane of cells, as well as receptor ligand recognition

Apical secretion of apolipoproteins from enterocytes

DEFF Research Database (Denmark)

Danielsen, E M; Hansen, Gert Helge; Poulsen, Mona Dam

1993-01-01

Synthesis and secretion of apolipoproteins in pig small intestine was studied by pulse-chase labeling of jejunal segments, kept in organ culture. Apo A-1 and apo B-48 were the two major proteins released, constituting 25 and 10%, respectively, of the total amount of labeled protein in the mucosal...... in the soluble fraction, suggesting a basolateral secretion into the intercellular space, and both this accumulation and the release to the medium was prevented by culture at 20 degrees C. The specific radioactivity of apo A-1 and apo B-48 released to the medium was significantly higher than...... that enterocytes release most of their newly made free apo A-1 and a significant portion of apo B-48 by exocytosis via the brush border membrane into the intestinal lumen. Fat absorption reduced apolipoprotein secretion to the medium and induced the formation of chylomicrons, containing apo A-1 at their surface...

Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

NARCIS (Netherlands)

Dallinga-Thie, G. M.; van Tol, A.; Hattori, H.; van Vark-van der Zee, L. C.; Jansen, H.; Sijbrands, E. J. G.

2006-01-01

Variation in the human apolipoprotein (APO) A5 gene (APOA5) is associated with elevated plasma triglycerides. However, data on the exact role of plasma concentrations of APOA5 in human triglyceride homeostasis are lacking. In the present study, we estimated plasma APOA5 levels in patients with type

Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

NARCIS (Netherlands)

Dallinga-Thie, GM; Van Tol, A; Hattori, H; van Vark-van de Zee, LC; Jansen, H; Sijbrands, EJG

Aims/hypothesis: Variation in the human apolipoprotein (APO) A5 gene (APOA5) is associated with elevated plasma triglycerides. However, data on the exact role of plasma concentrations of APOA5 in human triglyceride homeostasis are lacking. In the present study, we estimated plasma APOA5 levels in

Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

DEFF Research Database (Denmark)

Elsøe, Sara; Christoffersen, Christina; Luchoomun, Jayraz

2013-01-01

The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice.......The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice....

Backbone resonance assignments for G protein α(i3) subunit in the GDP-bound state.

Science.gov (United States)

Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

2014-10-01

Guanine-nucleotide binding proteins (G proteins) serve as molecular switches in signaling pathways, by coupling the activation of G protein-coupled receptors (GPCRs) at the cell surface to intracellular responses. In the resting state, G protein forms a heterotrimer, consisting of the G protein α subunit with GDP (Gα·GDP) and the G protein βγ subunit (Gβγ). Ligand binding to GPCRs promotes the GDP-GTP exchange on Gα, leading to the dissociation of the GTP-bound form of Gα (Gα·GTP) and Gβγ. Then, Gα·GTP and Gβγ bind to their downstream effector enzymes or ion channels and regulate their activities, leading to a variety of cellular responses. Finally, Gα hydrolyzes the bound GTP to GDP and returns to the resting state by re-associating with Gβγ. The G proteins are classified with four major families based on the amino acid sequences of Gα: i/o, s, q/11, and 12/13. Here, we established the backbone resonance assignments of human Gαi3, a member of the i/o family with a molecular weight of 41 K, in complex with GDP. The chemical shifts were compared with those of Gα(i3) in complex with a GTP-analogue, GTPγS, which we recently reported, indicating that the residues with significant chemical shift differences are mostly consistent with the regions with the structural differences between the GDP- and GTPγS-bound states, as indicated in the crystal structures. The assignments of Gα(i3)·GDP would be useful for the analyses of the dynamics of Gα(i3) and its interactions with various target molecules.

Apolipoprotein E and familial longevity

DEFF Research Database (Denmark)

Schupf, Nicole; Barral, Sandra; Perls, Thomas

2013-01-01

Exceptional longevity is associated with substantial heritability. The ε4 allele in apolipoprotein E and the linked G allele in rs2075650 of TOMM40 have been associated with increased mortality and the ε2 allele with decreased mortality, although inconsistently. Offspring from long-lived families...

Metrological traceability in mass spectrometry-based targeted protein quantitation: a proof-of-principle study for serum apolipoproteins A-I and B100.

Science.gov (United States)

Smit, Nico P M; Romijn, Fred P H T M; van den Broek, Irene; Drijfhout, Jan W; Haex, Martin; van der Laarse, Arnoud; van der Burgt, Yuri E M; Cobbaert, Christa M

2014-09-23

In this study, we have followed up on previous liquid chromatography (LC) multiple reaction monitoring (MRM) mass spectrometry (MS) approaches for measurement of apolipoprotein (apo) A-I and apo B100 in serum aiming for implementation of a multiplexed assay in a clinical chemistry laboratory with full metrological traceability. Signature peptides were selected and detected by dynamic MRM, and stable isotope labeled (SIL)-peptides were used as internal standards. Five apo A-I and four apo B100 peptides were measured in serum digests with linearity (R(2)>0.992) in the physiologically relevant concentration ranges. Linearity with regard to protein concentration was ascertained at five concentration levels (R(2)>0.926 and R(2)>0.965, for the apo A-I and apo B100 peptides, respectively). Three native value-assigned sera were used as external calibrators for further method verification. Imprecision values on sample preparation and LC-MS/MS acquisition were below the established minimal specifications for apo A-I and apo B100 (5.0% and 5.3%, respectively). Correlation of LC-MS/MS results with immunoturbidimetric assay results, for normo- and hypertriglyceridemic samples, showed R(2)>0.944 for apo A-I and R(2)>0.964 for apo B100. This LC-MS/MS method has potential for clinical application in normo- and dyslipidemic patients. Measurement of apo A-I and apo B100 may offer an alternative to high and low density lipoprotein cholesterol (HDL-c and LDL-c) methods for cardiovascular disease risk assessment in dyslipidemic patients [1]. An LC-MS/MS method for apo A-I and apo B100 has the advantage of antibody independent and specific detection of protein signature peptides. The introduction of an LC-MS/MS method for apo A-I and apo B100 can serve as an example for many existing and newly developed (multiplex) biomarker methods in quantitative clinical chemistry proteomics (qCCP). Such LC-MS/MS methods should meet basic clinical chemistry principles with regard to test evaluation

Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M

DEFF Research Database (Denmark)

Christoffersen, Christina; Obinata, Hideru; Kumaraswamy, Sunil B

2011-01-01

Protection of the endothelium is provided by circulating sphingosine-1-phosphate (S1P), which maintains vascular integrity. We show that HDL-associated S1P is bound specifically to both human and murine apolipoprotein M (apoM). Thus, isolated human ApoM(+) HDL contained S1P, whereas ApoM(-) HDL did...... not. Moreover, HDL in Apom(-/-) mice contains no S1P, whereas HDL in transgenic mice overexpressing human apoM has an increased S1P content. The 1.7-Å structure of the S1P-human apoM complex reveals that S1P interacts specifically with an amphiphilic pocket in the lipocalin fold of apoM. Human ApoM......(+) HDL induced S1P(1) receptor internalization, downstream MAPK and Akt activation, endothelial cell migration, and formation of endothelial adherens junctions, whereas apoM(-) HDL did not. Importantly, lack of S1P in the HDL fraction of Apom(-/-) mice decreased basal endothelial barrier function in lung...

cDNA sequences of two apolipoproteins from lamprey

International Nuclear Information System (INIS)

Pontes, M.; Xu, X.; Graham, D.; Riley, M.; Doolittle, R.F.

1987-01-01

The messages for two small but abundant apolipoproteins found in lamprey blood plasma were cloned with the aid of oligonucleotide probes based on amino-terminal sequences. In both cases, numerous clones were identified in a lamprey liver cDNA library, consistent with the great abundance of these proteins in lamprey blood. One of the cDNAs (LAL1) has a coding region of 105 amino acids that corresponds to a 21-residue signal peptide, a putative 8-residue propeptide, and the 76-residue mature protein found in blood. The other cDNA (LAL2) codes for a total of 191 residues, the first 23 of which constitute a signal peptide. The two proteins, which occur in the high-density lipoprotein fraction of ultracentrifuged plasma, have amino acid compositions similar to those of apolipoproteins found in mammalian blood; computer analysis indicates that the sequences are largely helix-permissive. When the sequences were searched against an amino acid sequence data base, rat apolipoprotein IV was the best matching candidate in both cases. Although a reasonable alignment can be made with that sequence and LAL1, definitive assignment of the two lamprey proteins to typical mammalian classes cannot be made at this point

Atherosclerosis, apolipoprotein E and the prevalence of dementia and Alzheimer's disease in a population-based study: the Rotterdam Study

NARCIS (Netherlands)

A. Ott (Alewijn); M.L. Bots (Michiel); A.J.C. Slooter (Arjen); F. van Harskamp (Frans); C.M. van Duijn (Cornelia); D.E. Grobbee (Diederick); M.M.B. Breteler (Monique); C. van Broeckhoven (Christine); A. Hofman (Albert)

1997-01-01

textabstractBACKGROUND: Vascular disorders have been implicated in dementia, but whether atherosclerosis is related to the most frequent type of dementia, Alzheimer's disease, is not known. The apolipoprotein-E genotype has been associated with Alzheimer's disease, and we postulate that it plays a

Apolipoprotein E in Temporal Lobe Epilepsy: A Case-Control Study

Directory of Open Access Journals (Sweden)

Amit Kumar

2006-01-01

Full Text Available Purpose: To investigate the relationship of apolipoprotein E (apoE genotype, plasma levels of apoE and lipids in temporal lobe epilepsy (TLE patients in Asian Indians. Status of plasma levels of Apo E in epilepsy patients has not been reported till date.

Atorvastatin decreases apolipoprotein C-III in apolipoprotein B-containing lipoprotein and HDL in type 2 diabetes: a potential mechanism to lower plasma triglycerides

NARCIS (Netherlands)

Dallinga-Thie, Geesje M.; Berk-Planken, Ingrid I. L.; Bootsma, Aart H.; Jansen, Hans

2004-01-01

Apolipoprotein (apo)C-III is a constituent of HDL (HDL apoC-III) and of apoB-containing lipoproteins (LpB:C-III). It slows the clearance of triglyceride-rich lipoproteins (TRLs) by inhibition of the activity of the enzyme lipoprotein lipase (LPL) and by interference with lipoprotein binding to

Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3 Protein Levels in Human-Derived Liver (HepG2) Cells.

Science.gov (United States)

Sayılan Özgün, Gülben; Özgün, Eray; Tabakçıoğlu, Kıymet; Süer Gökmen, Selma; Eskiocak, Sevgi; Çakır, Erol

2017-12-01

Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 are antioxidant and anti-atherosclerotic structural high-density lipoprotein proteins that are mainly synthesized by the liver. No study has ever been performed to specifically examine the effects of caffeine on paraoxonase enzymes and on liver apolipoprotein A-1 protein levels. To investigate the dose-dependent effects of caffeine on liver apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels. In vitro experimental study. HepG2 cells were incubated with 0 (control), 10, 50 and 200 μM of caffeine for 24 hours. Cell viability was evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels were measured by western blotting. We observed a significant increase on apolipoprotein A-1 and paraoxonase-1 protein levels in the cells incubated with 50 µM of caffeine and a significant increase on paraoxonase-1 protein level in the cells incubated with 200 µM of caffeine. Our study showed that caffeine does not change paraoxonase-3 protein level, but the higher doses used in our study do cause an increase in both apolipoprotein A-1 and paraoxonase-1 protein levels in liver cells.

Lower bounds for the minimum distance of algebraic geometry codes

DEFF Research Database (Denmark)

Beelen, Peter

, such as the Goppa bound, the Feng-Rao bound and the Kirfel-Pellikaan bound. I will finish my talk by giving several examples. Especially for two-point codes, the generalized order bound is fairly easy to compute. As an illustration, I will indicate how a lower bound can be obtained for the minimum distance of some...... description of these codes in terms of order domains has been found. In my talk I will indicate how one can use the ideas behind the order bound to obtain a lower bound for the minimum distance of any AG-code. After this I will compare this generalized order bound with other known lower bounds...

Analysis of a convenient information bound for general quantum channels

International Nuclear Information System (INIS)

O'Loan, C J

2007-01-01

Open questions from Sarovar and Milburn (2006 J. Phys. A: Math. Gen. 39 8487) are answered. Sarovar and Milburn derived a convenient upper bound for the Fisher information of a one-parameter quantum channel. They showed that for quasi-classical models their bound is achievable and they gave a necessary and sufficient condition for positive operator-valued measures (POVMs) attaining this bound. They asked (i) whether their bound is attainable more generally (ii) whether explicit expressions for optimal POVMs can be derived from the attainability condition. We show that the symmetric logarithmic derivative (SLD) quantum information is less than or equal to the SM bound, i.e., H(θ) ≤ C Y (θ) and we find conditions for equality. As the Fisher information is less than or equal to the SLD quantum information, i.e., F M (θ) ≤ H(θ), we can deduce when equality holds in F M (θ) ≤ C Y (θ). Equality does not hold for all channels. As a consequence, the attainability condition cannot be used to test for optimal POVMs for all channels. These results are extended to multi-parameter channels

The identification and nature of bound exciton I-line PL systems in ZnO

Energy Technology Data Exchange (ETDEWEB)

Johnston, K. [PH Dept, CERN, 1211-Geneva (Switzerland); Cullen, J.; Henry, M. O.; McGlynn, Enda [School of Physics Sciences, Dublin City University, Dublin 9 (Ireland); Khawaga, Rehab I. [Department of Chemistry, College of Art and Science, American University of Sharjah (AUS) (United Arab Emirates)

2013-12-04

The chemical identification of donor bound excitons in ZnO has been studied using radioactive ions. Implantations of {sup 117}Ag - which decays to radioactive Cd and In - have enabled the identification of the I{sub 2} optical feature as being the ionized donor counterpart of I{sub 9}, one of the most prominent optical features in the photoluminescence spectrum of ZnO. Both of these lines are consistent with In occupying a Zn site.

Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles

Science.gov (United States)

Nakamura, Shota; Ono, Chikako; Shiokawa, Mai; Yamamoto, Satomi; Motomura, Takashi; Okamoto, Toru; Okuzaki, Daisuke; Yamamoto, Masahiro; Saito, Izumu; Wakita, Takaji; Koike, Kazuhiko; Matsuura, Yoshiharu

2014-01-01

Apolipoprotein B (ApoB) and ApoE have been shown to participate in the particle formation and the tissue tropism of hepatitis C virus (HCV), but their precise roles remain uncertain. Here we show that amphipathic α-helices in the apolipoproteins participate in the HCV particle formation by using zinc finger nucleases-mediated apolipoprotein B (ApoB) and/or ApoE gene knockout Huh7 cells. Although Huh7 cells deficient in either ApoB or ApoE gene exhibited slight reduction of particles formation, knockout of both ApoB and ApoE genes in Huh7 (DKO) cells severely impaired the formation of infectious HCV particles, suggesting that ApoB and ApoE have redundant roles in the formation of infectious HCV particles. cDNA microarray analyses revealed that ApoB and ApoE are dominantly expressed in Huh7 cells, in contrast to the high level expression of all of the exchangeable apolipoproteins, including ApoA1, ApoA2, ApoC1, ApoC2 and ApoC3 in human liver tissues. The exogenous expression of not only ApoE, but also other exchangeable apolipoproteins rescued the infectious particle formation of HCV in DKO cells. In addition, expression of these apolipoproteins facilitated the formation of infectious particles of genotype 1b and 3a chimeric viruses. Furthermore, expression of amphipathic α-helices in the exchangeable apolipoproteins facilitated the particle formation in DKO cells through an interaction with viral particles. These results suggest that amphipathic α-helices in the exchangeable apolipoproteins play crucial roles in the infectious particle formation of HCV and provide clues to the understanding of life cycle of HCV and the development of novel anti-HCV therapeutics targeting for viral assembly. PMID:25502789

The X-X-/E+E+ genotype of the XbaI/EcoRI polymorphisms of the apolipoprotein B gene as a marker of coronary artery disease in a Brazilian sample

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M. Scartezini

2003-03-01

Full Text Available Studies that consider polymorphisms within the apolipoprotein B (apo B gene as risk factors for coronary artery disease (CAD have reported conflicting results. The aim of the present study was to search for associations between two DNA RFLPs (XbaI and EcoRI of the apo B gene and CAD diagnosed by angiography. In the present study we compared 116 Brazilian patients (92 men with CAD (CAD+ to 78 control patients (26 men without ischemia or arterial damage (CAD-. The allele frequencies at the XbaI (X and EcoRI (E sites did not differ between groups. The genotype distributions of CAD+ and CAD- patients were different (chi²(1 = 6.27, P = 0.012 when assigned to two classes (X-X-/E+E+ and the remaining XbaI/EcoRI genotypes. Multivariate logistic regression analysis showed that individuals with the X-X-/E+E+ genotype presented a 6.1 higher chance of developing CAD than individuals with the other XbaI/EcoRI genotypes, independently of the other risk factors considered (sex, tobacco consumption, total cholesterol, hypertension, and triglycerides. We conclude that the X-X-/E+E genotype may be in linkage disequilibrium with an unknown variation in the apo B gene or with a variation in another gene that affects the risk of CAD.

Influence of apolipoprotein-E gene on lipid profile, physical activity and body fat relationship. DOI:10.5007/1980-0037.2012v14n2p221

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Thales Boaventura Rachid Nascimento

2012-02-01

Full Text Available Physical activity and body fat modify lipemia, and this effect seems to be influenced by apolipoprotein-E (APOE gene polymorphism. Thus, the purpose of this article was to review main results of studies that have analyzed the relation of APOE gene with physical activity and body fat on triglycerides, total cholesterol and low (LDL and high density lipoprotein (HDL concentrations. The Scientific Electronic Library Online – SciELO, Web of Science and PubMed database were used to locate the articles. The keywords used in combination were: apoe genotype, apolipoprotein-E polymorphism, physical exercise, physical activity, aerobic exercise, body fat and obesity. Originals scientific investigations performed with humans were included, and excluded those ones which involved samples with diseases, except obesity and/or lipemic disorders. It was observed a trend, that ε2 allele carriers are the ones with the greater improvements on lipemia from physical exercise. In addition, the body fat impact on the elevation of triglycerides and LDL are stronger in carriers of the ε2 and ε4 allele, respectively. Considering the small number of originals scientific investigations and their divergent results, reliable inferences can not be made about the APOE gene polymorphism influences on physical activity and body fat effect on lipemia. Thus, further studies with others populations and more volunteers for allele, as well as others exercise modalities and intensities, are necessary.

Rapid radioimmunoassay of human apolipoproteins C-II and C-III

Energy Technology Data Exchange (ETDEWEB)

Gustafson, S; Oestlund-Lindqvist, A M; Vessby, B [Uppsala Univ. (Sweden)

1984-06-01

Apolipoprotein (apo) C-II is an activator of lipoprotein lipase, while apo C-III has the ability to inhibit apo C-II activated lipolysis. In order to study further the relationship between lipoprotein lipase mediated hydrolysis and the serum concentrations of apo C-II and apo C-III radioimmunoassays for these apolipoproteins have been developed. Formalin-treated Staphylococcus aureus Cowan I was used for immunoprecipitation and were shown to give rapid uptake of immune complexes that could easily be harvested by centrifugation. The assays were shown to be sensitive (10 ..mu..g/1), specific, precise (inter- and intra-assay coefficients of variation below 10%), rapid (completed in less than 6 h) and simple to perform. Delipidation of serum and lipoproteins had no effect on the results, indicating that the immunologically active sites of apo C-II and apo C-III are exposed to the aqueous environment under assay conditions. Serum apo C-II and apo C-III levels of normolipidaemic subjects were approximately 25 mg/1 and 110 mg/1, respectively. Highly significant positive correlations were found between VLDL apo C-II and VLDL apo C-III, respectively, and VLDL triglycerides, VLDL cholesterol and total serum TG. There was also a highly significant correlation between the HDL cholesterol concentration and the HDL apo C-III concentration.

Association between apolipoprotein E genotype, serum lipids, and colorectal cancer in Brazilian individuals

OpenAIRE

Souza, D.R.S.; Nakazone, M.A.; Pinhel, M.A.S.; Alvares, R.M.; Monaco, A.C.; Pinheiro, A.; Barros, C.F.D.C.; Cury, P.M.; Cunrath, G.S.; Netinho, J.G.

2009-01-01

We evaluated genetic variants of apolipoprotein E (APOE HhaI) and their association with serum lipids in colorectal cancer (CRC), together with eating habits and personal history. Eight-seven adults with CRC and 73 controls were studied. APOE*2 (rs7412) and APOE*4 (rs429358) were identified by polymerase chain reaction-restriction fragment length polymorphism. APOE gene polymorphisms were similar in both groups, but the ε4/ε4 genotype (6%) was present only in controls. The patients ...

Apolipoprotein M

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Nilsson-Ehle Peter

2004-10-01

Full Text Available Abstract Apolipoprotein M (apoM is a 26-kDa protein that is mainly associated with high-density lipoprotein (HDL in human plasma, with a small proportion present in triglyceride-rich lipoproteins (TGRLP and low-density lipoproteins (LDL. Human apoM gene is located in p21.31 on chromosome 6 (chromosome 17, in mouse. Human apoM cDNA (734 base pairs encodes 188-amino acid residue-long protein. It belongs to lipocalin protein superfamily. Human tissue expression array study indicates that apoM is only expressed in liver and in kidney and small amounts are found in fetal liver and kidney. In situ apoM mRNA hybridization demonstrates that apoM is exclusively expressed in the hepatocytes and in the tubule epithelial cells in kidney. Expression of apoM could be regulated by platelet activating factor (PAF, transforming growth factors (TGF, insulin-like growth factor (IGF and leptin in vivo and/or in vitro. It has been demonstrated that apoM expression is dramatically decreased in apoA-I deficient mouse. Hepatocyte nuclear factor-1α (HNF-1α is an activator of apoM gene promoter. Deficiency of HNF-1α mouse shows lack of apoM expression. Mutations in HNF-1α (MODY3 have reduced serum apoM levels. Expression of apoM is significantly decreased in leptin deficient (ob/ob mouse or leptin receptor deficient (db/db mouse. ApoM concentration in plasma is positively correlated to leptin level in obese subjects. These may suggest that apoM is related to the initiation and progression of MODY3 and/or obesity.

Interactions of metals and Apolipoprotein E in Alzheimer’s disease

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He eXu

2014-06-01

Full Text Available Alzheimer’s disease (AD is the most common form of dementia, which is characterized by the neuropathological accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs. Clinically, patients will endure a gradual erosion of memory and other higher order cognitive functions. Whilst the underlying etiology of the disease remains to be definitively identified, a body of work has developed over the last two decades demonstrating that AD plasma/serum and brain are characterized by a dyshomeostasis in a number of metal ions. Furthermore, these metals (such as zinc, copper and iron play roles in the regulation of the levels AD-related proteins, including the amyloid precursor protein (APP and tau. It is becoming apparent that metals also interact with other proteins, including apolipoprotein E (ApoE. The Apolipoprotein E gene (APOE is critically associated with AD, with APOE4 representing the strongest genetic risk factor for the development of late-onset AD whereas APOE2 appears to have a protective role. In this review we will summarize the evidence supporting a role for metals in the function of Apolipoprotein E (ApoE and its consequent role in the pathogenesis of AD.

Effects of apolipoprotein M in uremic atherosclerosis

DEFF Research Database (Denmark)

Bosteen, Markus Høybye; Madsen Svarrer, Eva Martha; Bisgaard, Line Stattau

2017-01-01

BACKGROUND AND AIMS: Chronic kidney disease is characterized by uremia and causes premature death, partly due to accelerated atherosclerosis. Apolipoprotein (apo) M is a plasma carrier protein for the lipid sphingosine-1-phosphate (S1P). The Apom-S1P complex associates with HDL, and may contribute...

A simple approach for human recombinant apolipoprotein E4 expression and purification.

Science.gov (United States)

Argyri, Letta; Skamnaki, Vassiliki; Stratikos, Efstratios; Chroni, Angeliki

2011-10-01

We report a simple expression and purification procedure for the production of recombinant apolipoprotein E4 (apoE4), an important protein for the lipid homeostasis in humans that plays critical roles in the pathogenesis of cardiovascular and neurodegenerative diseases. Our approach is based on the expression of a thioredoxin-apoE4 fusion construct in bacterial cells and subsequent removal of the fused thioredoxin using the highly specific 3C protease, avoiding costly and laborious lipidation-delipidation steps used before. Our approach results in rapid, high-yield production of structurally and functionally competent apoE4 as evidenced by secondary structure measurements, thermal and chemical melting profiles and the kinetic profile of solubilization of dimyristoyl-phosphatidylcholine (DMPC) vesicles. This protocol is appropriate for laboratories with little experience in apolipoprotein biochemistry and will facilitate future studies on the role of apoE4 in the pathogenesis of cardiovascular disease and neurodegenerative diseases, including Alzheimer's disease. Copyright © 2011 Elsevier Inc. All rights reserved.

Lipoprotein(a) accelerates atherosclerosis in uremic mice

DEFF Research Database (Denmark)

Pedersen, Tanja X; McCormick, Sally P; Tsimikas, Sotirios

2010-01-01

Uremic patients have increased plasma lipoprotein(a) [Lp(a)] levels and elevated risk of cardiovascular disease. Lp(a) is a subfraction of LDL, where apolipoprotein(a) [apo(a)] is disulfide bound to apolipoprotein B-100 (apoB). Lp(a) binds oxidized phospholipids (OxPL), and uremia increases lipop...

The binding of platinum hexahalides (Cl, Br and I) to hen egg-white lysozyme and the chemical transformation of the PtI{sub 6} octahedral complex to a PtI{sub 3} moiety bound to His15

Energy Technology Data Exchange (ETDEWEB)

Tanley, Simon W. M.; Starkey, Laurina-Victoria; Lamplough, Lucinda; Kaenket, Surasek; Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

2014-08-29

The platinum hexahalides have an octahedral arrangement of six halogen atoms bound to a Pt centre, thus having an octahedral shape that could prove to be useful in interpreting poor electron-density maps. In a detailed characterization, PtI{sub 6} chemically transformed to a square-planar PtI{sub 3} complex bound to the N{sup δ} atom of His15 of HEWL was also observed, which was not observed for PtBr{sub 6} or PtCl{sub 6}. This study examines the binding and chemical stability of the platinum hexahalides K{sub 2}PtCl{sub 6}, K{sub 2}PtBr{sub 6} and K{sub 2}PtI{sub 6} when soaked into pre-grown hen egg-white lysozyme (HEWL) crystals as the protein host. Direct comparison of the iodo complex with the chloro and bromo complexes shows that the iodo complex is partly chemically transformed to a square-planar PtI{sub 3} complex bound to the N{sup δ} atom of His15, a chemical behaviour that is not exhibited by the chloro or bromo complexes. Each complex does, however, bind to HEWL in its octahedral form either at one site (PtI{sub 6}) or at two sites (PtBr{sub 6} and PtCl{sub 6}). As heavy-atom derivatives of a protein, the octahedral shape of the hexahalides could be helpful in cases of difficult-to-interpret electron-density maps as they would be recognisable ‘objects’.

Serum apolipoprotein e level is not increased in Alzheimer's disease : The Rotterdam study

NARCIS (Netherlands)

Slooter, A.J.C.; Knijff, P. de; Hofman, A.; Cruts, M.; Breteler, M.M.B.; Broeckhoven, C. van; Havekes, L.M.; Duijn, C.M. van

1998-01-01

The APOE*4 allele of the apolipoprotein E gene (APOE) is an important risk factor for Alzheimer's disease. It has been suggested that levels of apolipoprotein E (apoE) in plasma are increased in Alzheimer's disease. In this population-based study, we found that serum apoE levels were lower in

Apolipoprotein M - a new biomarker in sepsis

DEFF Research Database (Denmark)

Christoffersen, Christina; Nielsen, Lars Bo

2012-01-01

Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship...... to severity of disease. This identifies apoM as a potential new biomarker in sepsis. It also underscores the possibility that altered high-density lipoprotein in sepsis patients can affect the course of disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule with great influence...... on vascular barrier function, the study presented raises the interest and relevance for further studies of apoM and S1P in relation to sepsis and inflammation....

Serum apolipoproteins in relation to intakes of fish in population of Arkhangelsk County

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Petrenya Natalia

2012-06-01

Full Text Available Abstract Background Diets rich in omega-3 fatty acids and low in saturated fat were found beneficially associated with blood lipids and cardio-vascular health. Lean reindeer meet and local cold water white-fish species high in omega-3 are among the main sources of nutrients in the rural area of the Nenets Autonomous Okrug (NAO in Russia and are not normally consumed by the urban population from the same region. The aims of the study were firstly, to compare serum lipid profiles of residents of urban (Arkhangelsk city and rural (NAO regions of Arkhangelsk County, and secondly, to investigate the effects of fish consumption on the predictor of cardiovascular events apolipoprotein (Apo B/ApoA-I ratio in these populations. Methods A cross-sectional study conducted in Arkhangelsk County, Russia. Sample size of 249 adults: 132 subjects from Arkhangelsk city, aged 21–70 and 117 subject (87% Ethnic Nenets from NAO, aged 18–69. Results We observed more favorable lipid levels in NAO compared to Arkhangelsk participants. Age-adjusted geometric means of ApoB/ApoA-I ratio were 1.02 and 0.98 in men and women from Arkhangelsk; 0.84 and 0.91 in men and women from NAO respectively. Age and consumption of animal fat were positively associated with ApoB/ApoA-I ratio in women (pooled samples from Arkhangelsk and NAO. Body mass index and low levels of physical activity were positively associated with ApoB/ApoA-I ratio in men (pooled samples from Arkhangelsk and NAO. Reported oily fish consumption was not significantly correlated with ApoB/ApoA-I ratio. Conclusion The population sample from rural NAO, consisting largely of the indigenous Arctic population Nenets with healthier dietary sources, had a relatively less atherogenic lipid profile compared to the urban Arkhangelsk group. Fish consumption had no effect on apolipoproteins profile.

Apolipoprotein M

DEFF Research Database (Denmark)

Christoffersen, Christina; Dahlbäck, B; Nielsen, L B

2006-01-01

ApoM is a novel apolipoprotein mainly present in high-density lipoprotein (HDL). It belongs to the lipocalin protein superfamily and may bind a small but so far unknown lipophilic ligand. It is secreted without cleavage of its hydrophobic signal peptide, which probably anchors apoM...... in the phospholipid moiety of plasma lipoproteins. Recent studies suggest that apoM may affect HDL metabolism and have anti-atherogenic functions. The subfraction of human HDL that contains apoM therefore protects LDL from oxidation and mediates cholesterol efflux more efficiently then HDL without apoM. In addition...... to hepatocytes, apoM is highly expressed in kidney proximal tubule cells. Recent data suggest that apoM is secreted into the pre-urine from the tubule cells but is normally taken up again in a megalin-dependent fashion. Further studies of mice with genetically modified apoM expression will be essential...

Differential interaction of Apolipoprotein-E isoforms with insulin receptors modulates brain insulin signaling in mutant human amyloid precursor protein transgenic mice.

Science.gov (United States)

Chan, Elizabeth S; Chen, Christopher; Cole, Gregory M; Wong, Boon-Seng

2015-09-08

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.

Electroimmunoassay, radioimmunoassay, and radial immunodiffusion assay evaluated for quantification of human apolipoprotein B

International Nuclear Information System (INIS)

Curry, M.D.; Gustafson, A.; Alaupovic, P.; McConathy, W.J.

1978-01-01

We examined three immunoassay techniques for measuring apolipoprotein B in serum and major lipoprotein density fractions from normolipidemic and hyperlipoproteinemic persons, comparing values by electroimmunoassay, radioimmunoassay, and radial immunodiffusion assay with those determined gravimetrically. Electroimmunoassay is faster and simpler than radioimmunoassay, and equally precise (within- and between-assay coefficients of variation for both were 5 and 7%, respectively). All the immunoassays gave results that agreed with those by gravimetry for normolipidemic sera and the corresponding lipoprotein density fractions, but only electroimmunoassay results agreed with those by gravimetry for apolipoprotein B in lipoproteins of d < 1.019 g/ml isolated from hypertriglyceridemic patients. Concentrations of apolipoprotein B in plasma, determined by electroimmunoassay in a population of normal persons and patients with primary hyperlipoproteinemias, were: normals, 980 +- 200; type 1, 700 +- 160; type IIa, 2000 +- 260; type IIb, 2180 +- 300; type III, 1300 +- 340; type IV, 1470 +- 400; and type V, 1550 +- 390 mg/liter (mean +- SD). Lipoprotein density fractions from the hyperlipoproteinemic patients each had a characteristic distribution of free and associated forms of lipoprotein family B. The absolute concentration and distribution of apolipoprotein B between the free and associated forms of lipoprotein B may represent a useful indicator of the underlying biochemical defect

Majorana bound states in a disordered quantum dot chain

International Nuclear Information System (INIS)

Zhang, P; Nori, Franco

2016-01-01

We study Majorana bound states in a disordered chain of semiconductor quantum dots proximity-coupled to an s -wave superconductor. By calculating its topological quantum number, based on the scattering-matrix method and a tight-binding model, we can identify the topological property of such an inhomogeneous one-dimensional system. We study the robustness of Majorana bound states against disorder in both the spin-independent terms (including the chemical potential and the regular spin-conserving hopping) and the spin-dependent term, i.e., the spin-flip hopping due to the Rashba spin–orbit coupling. We find that the Majorana bound states are not completely immune to the spin-independent disorder, especially when the latter is strong. Meanwhile, the Majorana bound states are relatively robust against spin-dependent disorder, as long as the spin-flip hopping is of uniform sign (i.e., the varying spin-flip hopping term does not change its sign along the chain). Nevertheless, when the disorder induces sign-flip in spin-flip hopping, the topological-nontopological phase transition takes place in the low-chemical-potential region. (paper)

Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil

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Sumeet S Mitter

2012-01-01

Full Text Available OBJECTIVE: Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children. METHODS: A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ received 200,000 IU of retinol (every four months, zinc (40 mg twice weekly, or both for one year, with half of each group receiving glutamine supplementation for 10 days. Height-for-age z-scores, weight-for-age z-scores, weight-forheight z-scores, and lactulose:mannitol ratios were assessed during the initial four months of treatment. An average of four years (range 1.4-6.6 later, the children underwent cognitive testing to evaluate non-verbal intelligence, coding, verbal fluency, verbal learning, and delayed verbal learning. Apolipoprotein E4 carriage was determined by PCR analysis for 144 children. RESULTS: Thirty-seven children were apolipoprotein E4(+, with an allele frequency of 13.9%. Significant associations were found for vitamin A and glutamine with intestinal barrier function. Apolipoprotein E4(+ children receiving glutamine presented significant positive Pearson correlations between the change in height-for-age z-scores over four months and delayed verbal learning, along with correlated changes over the same period in weight-for-age z-scores and weight-for-height z-scores associated with non-verbal intelligence quotients. There was a significant correlation between vitamin A supplementation of apolipoprotein E4(+ children and improved delta lactulose/mannitol. Apolipoprotein E4(- children, regardless of intervention, exhibited negative Pearson correlations between the change in lactulose-to-mannitol ratio over four months and verbal learning and non-verbal intelligence. CONCLUSIONS: During development, apolipoprotein E4 may

Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins

DEFF Research Database (Denmark)

Varkey, Jobin; Isas, Jose Mario; Mizuno, Naoko

2010-01-01

Synucleins and apolipoproteins have been implicated in a number of membrane and lipid trafficking events. Lipid interaction for both types of proteins is mediated by 11 amino acid repeats that form amphipathic helices. This similarity suggests that synucleins and apolipoproteins might have...... of amphipathic helices alone. Moreover, we frequently observed that a-synuclein caused membrane structures that had the appearance of nascent budding vesicles. The ability to function as a minimal machinery for vesicle budding agrees well with recent findings that a-synuclein plays a role in vesicle trafficking...

Bounded dust-acoustic waves in a cylindrically bounded collisional dusty plasma with dust charge variation

International Nuclear Information System (INIS)

Wei Nanxia; Xue Jukui

2006-01-01

Taking into account the boundary, particle collisions, and dust charging effects, dust-acoustic waves in a uniform cylindrically bounded dusty plasma is investigated analytically, and the dispersion relation for the dust-acoustic wave is obtained. The effects of boundary, dust charge variation, particle collision, and dust size on the dust-acoustic wave are discussed in detail. Due to the bounded cylindrical boundary effects, the radial wave number is discrete, i.e., the spectrum is discrete. It is shown that the discrete spectrum, the adiabatic dust charge variation, dust grain size, and the particle collision have significant effects on the dust-acoustic wave

Common and Rare Alleles in Apolipoprotein B Contribute to Plasma Levels of LDL Cholesterol in the General Population

DEFF Research Database (Denmark)

Benn, M; Stene, MC; Nordestgaard, BG

2008-01-01

demonstrated to affect low-density lipoprotein (LDL) cholesterol levels. OBJECTIVE: We tested the hypothesis that nonsynonymous SNPs in three important functional domains of APOB and APOB tag SNPs predict levels of LDL cholesterol and apolipoprotein B and risk of ischemic heart disease. DESIGN......: This was a prospective study with 25 yr 100% follow up, The Copenhagen City Heart Study. SETTING: The study was conducted in the Danish general population. PARTICIPANTS: Participants included 9185 women and men aged 20-80+ yr. MAIN OUTCOME MEASURES: Levels of LDL cholesterol and apolipoprotein B and risk of ischemic......Q (0.09), E4154K (0.17), and N4311S (0.21). SNPs were associated with increases (T71I, Ivs181708g>t, T2488Tc>t, R3611) or decreases (Ivs4+171c>a, A591V, Ivs18+379a>c, P2712L, E4154, N4311S) in LDL cholesterol from -4.7 to +8.2% (-0.28 to 0.30 mmol/liter; P

Impact of lipoprotein(a) levels and apolipoprotein(a) isoform size on risk of coronary heart disease

NARCIS (Netherlands)

Hopewell, J. C.; Seedorf, U.; Farrall, M.; Parish, S.; Kyriakou, T.; Goel, A.; Hamsten, A.; Collins, R.; Watkins, H.; Clarke, R.; van der Hout, Annemarie H.

Objectives. Observational and genetic studies have shown that lipoprotein(a) [Lp(a)] levels and apolipoprotein( a) [apo(a)] isoform size are both associated with coronary heart disease (CHD) risk, but the relative independence of these risk factors remains unclear. Clarification of this uncertainty

Universality and stationarity of the I-Love relation for self-bound stars

Science.gov (United States)

Chan, T. K.; Chan, AtMa P. O.; Leung, P. T.

2016-01-01

The emergence of the I-Love-Q relations, revealing that the moment of inertia, the tidal Love number (deformability) and the spin-induced quadrupole moment of compact stars are, to high accuracy, interconnected in a universal way disregarding the wide variety of equations of state (EOSs) of dense matter, has attracted much interest recently. However, the physical origin of these relations is still a debatable issue. In the present paper, we focus on the I-Love relation for self-bound stars (SBSs) such as incompressible stars and quark stars. We formulate perturbative expansions for the moment of inertia, the tidal Love number (deformability) and the I-Love relation of SBSs. By comparing the respective I-Love relations of incompressible stars and a specific kind of SBSs, we show analytically that the I-Love relation is, to relevant leading orders in stellar compactness, stationary with respect to changes in the EOS about the incompressible limit. Hence, the universality of the I-Love relation is indeed attributable to the proximity of compact stars to incompressible stars, and the stationarity of the relation as unveiled here. We also discover that the moment of inertia and the tidal deformability of a SBS with finite compressibility are, to leading order in compactness, equal to their counterparts of an incompressible star with an adjusted compactness, thus leading to a novel explanation for the I-Love universal relation.

Association of apolipoprotein b/apolipoprotein A1 ratio and coronary artery stenosis and plaques detected by multi-detector computed tomography in healthy population.

Science.gov (United States)

Jung, Chang Hee; Hwang, Jenie Yoonoo; Shin, Mi Seon; Yu, Ji Hee; Kim, Eun Hee; Bae, Sung Jin; Yang, Dong Hyun; Kang, Joon-Won; Park, Joong-Yeol; Kim, Hong-Kyu; Lee, Woo Je

2013-05-01

Despite the noninvasiveness and accuracy of multidetector computed tomography (MDCT), its use as a routine screening tool for occult coronary atherosclerosis is unclear. We investigated whether the ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1), an indicator of the balance between atherogenic and atheroprotective cholesterol transport could predict occult coronary atherosclerosis detected by MDCT. We collected the data of 1,401 subjects (877 men and 524 women) who participated in a routine health screening examination of Asan Medical Center. Significant coronary artery stenosis defined as > 50% stenosis was detected in 114 subjects (8.1%). An increase in apoB/A1 quartiles was associated with increased percentages of subjects with significant coronary stenosis and noncalcified plaques (NCAP). After adjustment for confounding variables, each 0.1 increase in serum apoB/A1 was significantly associated with increased odds ratios (ORs) for coronary stenosis and NCAP of 1.23 and 1.18, respectively. The optimal apoB/A1 ratio cut off value for MDCT detection of significant coronary stenosis was 0.58, which had a sensitivity of 70.2% and a specificity of 48.2% (area under the curve, 0.61; 95% CI, 0.58-0.63, P < 0.001). Our results indicate that apoB/A1 ratio is a good indicator of occult coronary atherosclerosis detected by coronary MDCT.

Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation

DEFF Research Database (Denmark)

Bartels, Emil D; Ploug, Thorkil; Størling, Joachim

2014-01-01

Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design. In t...... accumulation and attenuates peripheral insulin resistance in obese mice........ In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apo......Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design...

Birth Weight, Cord Blood Lipoprotein and Apolipoprotein Levels in Indian Newborns

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Simmi Kharb

2010-01-01

Full Text Available Objectives: Primordial prevention of chronic disease is of clinical andpublic health importance. Considering the fetal onset of atherosclerosis,we aimed to determine the cord blood level of lipoproteins andapolipoproteins as well as their correlation with birth weight and gestationalage.Methods: This cross-sectional study comprised 100 healthy Indiannewborns. Ten ml. of cord blood was collected from placental end ofumbilical vein. Serum was separated by centrifugation and analyzed onthe same day for lipid profile including total cholesterol (TC, triglycerides(TG, high density lipoprotein- cholesterol (HDL-C, very lowdensity lipoprotein-cholesterol (VLDL and low density lipoproteincholesterol(LDL-C, apolipoproteins A-I and B (ApoA-I, ApoB.Atherogenic index (AI was calculated as the ratio of ApoB to ApoA-I.Results: Cord blood of female newborns had higher TC, HDL-C,LDL-C, Apo A-I, Apo B and AI as compared to male newborns,whereas TG and VLDL-C were higher in male than in female newborns.Significant positive correlation was observed between cordblood Apo A-I and HDL-C (r= 0.45, p0.05.Conclusions: These findings are another confirmatory evidence forthe association of prenatal factors with cord blood lipid profile, andcan serve as starting point for studying lipid transport system changesduring early life.

Dietary Flaxseed Oil Prevents Western-Type Diet-Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein-E Knockout Mice

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Hao Han

2017-01-01

Full Text Available The prevalence of nonalcoholic fatty liver disease (NAFLD has dramatically increased globally during recent decades. Intake of n-3 polyunsaturated fatty acids (PUFAs, mainly eicosapentaenoic acid (EPA, C20:5n-3 and docosahexaenoic acid (DHA, C22:6n-3, is believed to be beneficial to the development of NAFLD. However, little information is available with regard to the effect of flaxseed oil rich in α-linolenic acid (ALA, C18:3n-3, a plant-derived n-3 PUFA, in improving NAFLD. This study was to gain the effect of flaxseed oil on NAFLD and further investigate the underlying mechanisms. Apolipoprotein-E knockout (apoE-KO mice were given a normal chow diet, a western-type high-fat and high-cholesterol diet (WTD, or a WTD diet containing 10% flaxseed oil (WTD + FO for 12 weeks. Our data showed that consumption of flaxseed oil significantly improved WTD-induced NAFLD, as well as ameliorated impaired lipid homeostasis, attenuated oxidative stress, and inhibited inflammation. These data were associated with the modification effects on expression levels of genes involved in de novo fat synthesis (SREBP-1c, ACC, triacylglycerol catabolism (PPARα, CPT1A, and ACOX1, inflammation (NF-κB, IL-6, TNF-α, and MCP-1, and oxidative stress (ROS, MDA, GSH, and SOD.

Oligomeric protein complexes of apolipoproteins stabilize the internal fluid environment of organism in redfins of the Tribolodon genus [Pisces; Cypriniformes, Cyprinidae].

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Andreeva, Alla M; Serebryakova, Marina V; Lamash, Nina E

2017-06-01

One of the most important functions of plasma proteins in vertebrates is their participation in osmotic homeostasis in the organism. Modern concepts about plasma proteins and their capillary filtration are based on a model of large monomeric proteins that are able to penetrate the interstitial space. At the same time, it was revealed that a considerable amount of oligomeric complexes are present in the low-molecular-weight (LM) protein fraction in the extracellular fluids of fishes. The functions of these complexes are unknown. In the present study, we investigated the LM-fraction proteins in the plasma and interstitial fluid (IF) of redfins of the genus Tribolodon. This fish alternatively spends parts of its life cycle in saline and fresh waters. We identified the protein Wap65, serpins and apolipoproteins in this fraction. By combining the methods of 2D-E under native and denaturing conditions with MALDI, we demonstrated that only apolipoproteins formed complexes. We showed that serum apolipoproteins (АроА-I, Аро-14) were present in the form of homooligomeric complexes that were dissociated with the release of monomeric forms of proteins in the course of capillary filtration to IF. Dissociation of homooligomers is not directly correlated with the change in salinity but is correlated with seasonal dynamics. We found that there was a significant decrease in the total protein concentration in IF relative to plasma. Therefore, we suggested that dissociation of homooligomeric complexes from various apolipoproteins supports the isoosmoticity of extracellular fluids relative to capillary wall stabilization through a fluid medium in fish. Copyright © 2017 Elsevier Inc. All rights reserved.

Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding

International Nuclear Information System (INIS)

Innerarity, T.L.; Weisgraber, K.H.; Arnold, K.S.; Mahley, R.W.; Krauss, R.M.; Vega, G.L.; Grundy, S.M.

1987-01-01

Previous in vivo turnover studies suggested that retarded clearance of low density lipoproteins (LDL) from the plasma of some hypercholesterolemic patients is due to LDL with defective receptor binding. The present study examined this postulate directly by receptor binding experiments. The LDL from a hypercholesterolemic patient (G.R.) displayed a reduced ability to bind to the LDL receptors on normal human fibroblasts. The G.R. LDL possessed 32% of normal receptor binding activity. Likewise, the G.R. LDL were much less effective than normal LDL in competing with 125 I-labeled normal LDL for cellular uptake and degradation and in stimulating intracellular cholesteryl ester synthesis. The defect in LDL binding appears to be due to a genetic abnormality of apolipoprotein B-100: two brothers of the proband possess LDL defective in receptor binding, whereas a third brother and the proband's son have normally binding LDL. Further, the defect in receptor binding does not appear to be associated wit an abnormal lipid composition or structure of the LDL. Normal and abnormal LDL subpopulations were partially separated from plasma of two subjects by density-gradient ultracentrifugation, a finding consistent with the presence of a normal and a mutant allele. The affected family members appear to be heterozygous for this disorder, which has been designated familial defective apolipoprotein B-100. These studies indicate that the defective receptor binding results in inefficient clearance of LDL and the hypercholesterolemia observed in these patients

Increase of arginase activity in old apolipoprotein-E deficient mice under Western diet associated with changes in neurovascular unit

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Badaut Jérôme

2012-06-01

Full Text Available Abstract Aging and atherosclerosis are well-recognized risk factors for cardiac and neurovascular diseases. The Apolipoprotein E deficient (ApoE−/− mouse on a high-fat diet is a classical model of atherosclerosis, characterized by the presence of atherosclerotic plaques in extracranial vessels but not in cerebral arteries. Increase in arginase activity was shown to participate in vascular dysfunction in the peripheral arteries of atherosclerotic mice by changing the level of nitric oxide (NO. NO plays a key role in the physiological functions of the neurovascular unit (NVU. However, the regulation of arginase expression and activity in the brain was never investigated in association with changes in the NVU, ApoE deficiency and high fat diet. Fourteen-month-old ApoE−/− mice on high-fat diet exhibited deposition of lipids in the NVU, impairment of blood–brain barrier properties, astrogliosis and an increase of aquaporin 4 staining. In association with these changes, brain arginase activity was significantly increased in the old ApoE−/− mice as compared to old wild type mice, with an increase in the level of arginase type I in the blood vessels. In conclusion, aging in this classical mouse model of atherosclerosis induces an increase in the level and activity of arginase I that may impair NO synthesis and contribute to changes in the NVU leading to blood–brain barrier leakage and inflammation.

Apolipoprotein E in Temporal Lobe Epilepsy: A Case-Control Study

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Kumar, Amit; Tripathi, Manjari; Pandey, Ravindra M.; Ramakrishnan, Lakshmy; Srinivas, M.; Luthra, Kalpana

2006-01-01

Purpose: To investigate the relationship of apolipoprotein E (apoE) genotype, plasma levels of apoE and lipids in temporal lobe epilepsy (TLE) patients in Asian Indians. Status of plasma levels of Apo E in epilepsy patients has not been reported till date. Methods: ApoE gene polymorphism was analyzed in 58 patients with temporal lobe epilepsy (TLE) and 57 age and sex approximated controls using Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Levels of plasma apoE and lipids were measured using ELISA and enzymatic kits respectively. Results: The distribution of ApoE genotype in epilepsy patients and controls was comparable. Higher levels of plasma ApoE were observed in TLE patients as compared to controls (p = 0.0001). Individuals with plasma levels of apoE > 190 mg/L were at 20 times higher odds (95%CI = 2.46–163.34, p = 0.005), while those with levels of apoE between 150–190 mg/L were at 4.9 times higher odds (95% CI = 1.85–13.9, p = 0.001), to develop TLE. Conclusions: We have observed for the first time, high levels of plasma apoE in epilepsy patients. The findings of this case-control study suggest that apolipoprotein E may play an important role in epilepsy. PMID:17264404

Apolipoprotein E and carotid artery atherosclerosis - The Rotterdam study

NARCIS (Netherlands)

Slooter, AJC; Bots, ML; Havekes, LM; del Sol, AI; Cruts, M; Grobbee, DE; Hofman, A; Van Broeckhoven, C; Witteman, JCM; van Duijn, CM

Background and Purpose-Carotid artery atherosclerosis is a strong predictor for future stroke. It is yet unclear whether the apolipoprotein E polymorphism (APOE) is related to atherosclerosis in the carotid arteries. The aim of the present study was to investigate the role of APOE in carotid artery

Lying for the Greater Good: Bounded Rationality in a Team

OpenAIRE

Oktay Sürücü

2014-01-01

This paper is concerned with the interaction between fully and boundedly rational agents in situations where their interests are perfectly aligned. The cognitive limitations of the boundedly rational agent do not allow him to fully understand the market conditions and lead him to take non-optimal decisions in some situations. Using categorization to model bounded rationality, we show that the fully rational agent can nudge, i.e., he can manipulate the information he sends and decrease the exp...

Lying for the Greater Good: Bounded Rationality in a Team

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Oktay Sürücü

2014-10-01

Full Text Available This paper is concerned with the interaction between fully and boundedly rational agents in situations where their interests are perfectly aligned. The cognitive limitations of the boundedly rational agent do not allow him to fully understand the market conditions and lead him to take non-optimal decisions in some situations. Using categorization to model bounded rationality, we show that the fully rational agent can nudge, i.e., he can manipulate the information he sends and decrease the expected loss caused by the boundedly rational agent. Assuming different types for the boundedly rational agent, who differ only in the categories used, we show that the fully rational agent may learn the type of the boundedly rational agent along their interaction. Using this additional information, the outcome can be improved and the amount of manipulated information can be decreased. Furthermore, as the length of the interaction increases the probability that the fully rational agent learns the type of the boundedly rational agent grows

Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

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García-Arias Carlota

2009-06-01

Full Text Available Abstract Background Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. Methods Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases and 31 patients with severe hypertriglyceridaemia (controls were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. Results Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS. Conclusion Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood.

Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

Science.gov (United States)

2009-01-01

Background Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. Methods Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. Results Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS). Conclusion Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood. PMID:19534808

Increased plasma apolipoprotein (a) levels in IDDM patients with diabetic nephropathy

DEFF Research Database (Denmark)

Tarnow, L; Rossing, P; Nielsen, F S

1996-01-01

OBJECTIVE: The relative mortality from cardiovascular disease (CVD) is increased 40-fold in IDDM patients suffering from diabetic nephropathy as compared with nondiabetic subjects on average. We assessed the potential contribution of dyslipidemia in general and elevated serum apolipoprotein (a.......0001. Multiple logistic regression analysis of cardiovascular risk factors revealed that plasma apo(a) concentration > 300 U/l is an independent risk factor for coronary heart disease, odds ratio 1.86 (1.03-3.36) (P Dyslipidemia and raised plasma concentrations of apo(a), particularly > 300...

Apolipoprotein A-I and B levels, dyslipidemia and metabolic syndrome in south-west Chinese women with PCOS.

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Zhang, Jinxia; Fan, Ping; Liu, Hongwei; Bai, Huai; Wang, Ying; Zhang, Feng

2012-08-01

What are the relationships between apolipoprotein (apo) A-I and apoB concentrations, the apoB/apoA-I ratio and the prevalences of dyslipidemia and metabolic syndrome (MS) in south-west Chinese women with polycystic ovary syndrome (PCOS). There is a relatively high incidence of dyslipidemia and MS in south-west Chinese women with PCOS, especially in patients without hyperandrogenism. Patients with dyslipidemia are more obese, and have a more adverse glucose and lipid metabolic profile and higher apoB levels and apoB/apoA-I ratio. The increased apoB levels and apoB/A1 ratio and the MS are strongly associated with PCOS, suggesting that there is an increased risk of cardiovascular diseases in these patients. Dyslipidemia and MS have been widely studied in women with PCOS, but to date no data from south-west Chinese subjects have been available. The apoB/apoA-I ratio has been reported to be strongly associated with MS and insulin resistance (IR) and to be a reliable parameter that reflects lipid disturbances and the potential to develop atherosclerosis, but its relationship with PCOS is unclear. DESIGN This case-control study included 406 patients with PCOS and 342 control women between 17 and 40 years of age from a population in south-west China during 2006-2011. The diagnosis of PCOS was based on the revised 2003 Rotterdam criteria. The control group, consisting of women with infertility due to a Fallopian obstruction or the husband's infertility, women undergoing a pre-pregnancy check and healthy volunteers, was recruited from the same hospital during the same period. All women were not taking any medication known to affect carbohydrate or lipid or hormone metabolism for at least 3 months prior to the study, and were studied during the follicular phase of their menstrual cycle. MS was assessed by the National Cholesterol Education Program-Adult treatment Panel (NCEP-ATP) III criteria modified for Asian populations. Dyslipidemia was defined by one or more of the

Apolipoprotein B, the villain in the drama?

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Yu, Qi; Zhang, Yaping; Xu, Cang-Bao

2015-02-05

Low-density lipoprotein (LDL) is the major atherogenic lipoprotein and the primary target of lipid-lowering therapy for treating ischemic cardiovascular disease. Apolipoprotein B (apoB), an important structural component of LDL, plays a key role in cholesterol transport and removal in vascular wall. On the other hand, under pathological process, apoB interacts with the arterial wall to initiate the cascade of events that leads to atherosclerosis. However, interactions between apoB and vascular wall remain to be determined. Here, we address a pathological role of apoB per se and whole LDL particle in dysfunction of vascular endothelium and smooth muscle cells i.e. decreased endothelium-dependent vasodilation and increased receptor-mediated vasoconstriction. We intend to discuss: i) how apoB is responsible for the deleterious effects of LDL in the development of ischemic cardiovascular disease; ii) why vaccine based on peptides derived from apoB-100 is a promising therapy for treating ischemic cardiovascular disease, and iii) direct inhibition of apoB production should be a better therapeutic option than simple LDL-cholesterol lowering therapy in the patients with severe hypercholesterolemia at high cardiovascular risk with statin intolerance. In conclusion, apoB, but not cholesterol, plays a major role in LDL-induced dysfunction of endothelium, suggesting that direct apoB-targeting agents might be a promising therapy for the treatment of ischemic cardiovascular disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Lipoprotein (a)--lipid profile and apolipoprotein B in children of young parents with coronary artery disease.

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Khalil, Anita; Aggarwal, Amit; Arora, Sarika; Bhattacharya, Jayashree

2011-01-01

To evaluate lipoprotein(a), apolipoprotein B and lipid profile in children of young parents with coronary artery disease. Analytical observational study. Tertiary care hospital. The study included 80 children (9-18 years) out of which 40 were children of young parents (one or both) with established coronary artery disease (CAD), while the other 40 were children of parents with no evidence of CAD (controls). All were evaluated for fasting blood glucose, lipid profile, apolipoprotein B and lipoprotein (a) - Lp(a). Two sample 't' test was applied for analysis of continuous variables between study & control group. The study group children had significantly higher levels of total serum cholesterol (p = 0.004), LDL cholesterol (p = 0.002), lipoprotein a (p = 0.001) as compared to children of the control group. A significant difference in apolipoprotein B levels (p = 0.044) was observed in children in the adolescent age group (14-18 years). Both systolic and diastolic blood pressures were significantly higher without any significant difference being observed for weight and body mass index between the two groups. Higher levels of pro-atherogenic factors in children with family history of premature CAD indicate that the combined effects of "nature and nurture" are responsible for development of accelerated atherosclerosis especially in Indians. Tracking of Lp(a) levels from childhood may be a better option than detecting other elements of dyslipidemia which are not fully expressed until middle age.

Comparison of lipoprotein electrophoresis and apolipoprotein e genotyping in investigating dysbetalipoproteinemia

International Nuclear Information System (INIS)

Ahmed, F.; Kadiki, A.E.

2017-01-01

Dysbetalipoproteinemia is often associated with apolipoprotein E2E2 homozygosity; however, lipoprotein electrophoresis may also be used to assist in the diagnosis. The aim of this study was to compare apolipoprotein E (apo E) genotyping and lipoprotein electrophoresis in investigating dysbetalipoproteinemia. Data were collected over a three-year period from a lipid clinic in a tertiary referral centre and reviewed for apo E genotyping and lipoprotein electrophoresis. Sixty-two patients had both apo E genotyping and lipoprotein electrophoresis. Of these, 16 patients showed broad beta band on electrophoresis. However, only 3 of them had apo E2E2 homozygosity on genotyping. Lipoprotein electrophoresis and apo E genotyping results showed poor concordance. This was primarily due to visual interpretation error of lipoprotein electrophoresis which may over diagnose dysbetalipoproteinemia. (author)

Comparison of Lipoprotein Electrophoresis and Apolipoprotein E Genotyping in Investigating Dysbetalipoproteinemia.

Science.gov (United States)

Ahmed, Farhan; El-Kadiki, Alia; Gibbons, Stephen

2017-06-01

Dysbetalipoproteinemia is often associated with apolipoprotein E2E2 homozygosity; however, lipoprotein electrophoresis may also be used to assist in the diagnosis. The aim of this study was to compare apolipoprotein E (apo E) genotyping and lipoprotein electrophoresis in investigating dysbetalipoproteinemia. Data were collected over a three-year period from a lipid clinic in a tertiary referral centre and reviewed for apo E genotyping and lipoprotein electrophoresis. Sixty-two patients had both apo E genotyping and lipoprotein electrophoresis. Of these, 16 patients showed broad beta band on electrophoresis. However, only 3 of them had apo E2E2 homozygosity on genotyping. Lipoprotein electrophoresis and apo E genotyping results showed poor concordance. This was primarily due to visual interpretation error of lipoprotein electrophoresis which may over diagnose dysbetalipoproteinemia.

The relation between dietary intake of vegetable oils and serum lipids and apolipoprotein levels in central Iran

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Hossein Khosravi Boroujeni

2012-01-01

Full Text Available BACKGROUND: The detrimental effects of partially hydrogenated vegetable oils (PHVOs on apolipoproteins have been reported from several parts of the world. However, little data is available in this regard from the understudied region of the Middle East. The present study therefore tried to evaluate the association between type of vegetable oils and serum lipids and apolipoprotein levels among Iranians. METHODS: In this cross-sectional study, data from 1772 people (795 men and 977 women aged 19-81 years, who were selected with multistage cluster random sampling method from three cities of Isfahan, Najaf Abad and Arak in "Isfahan Healthy Heart Program" (IHHP, was used. To assess participants' usual dietary intakes, a validated food frequency questionnaire was used. Hydrogenated vegetable oil (commonly consumed for cooking in Iran and margarine were considered as the category of PHVOs. Soy, sunflower, corn, olive and canola oils were considered as non-HVOs. After an overnight fasting, serum cholesterol (total, low density lipoprotein (LDL and high density lipoprotein (HDL cholesterol and triglyceride as well as apolipoproteins A and B were measured using standard methods. RESULTS: Participants with the highest intakes of non-HVOs and PHVOs were younger and had lower weight than those with lowest intakes. High consumption of non-HVOs and PHVOs was associated with lower intakes of energy, carbohydrate, dietary fiber, and higher intakes of fruits, vegetables, meat, milk and grains. No overall significant differences were found in serum lipids and apolipoprotein levels across the quartiles of non-HVOs and PHVOs after controlling for potential confounding. CONCLUSION: We did not find any significant associations between hydrogenated or non-hydrogenated vegetable oil and serum lipid and apolipoprotein levels. Thus, further studies are needed in this region to explore this association. Keywords: Vegetable Oils, Cardiovascular Risk Factors, Lipids

Changes in total and central fat mass after a hypocaloric diet associate with changes of apoC-I in postmenopausal obese women.

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Wassef, Hanny; Davignon, Jean; Prud'homme, Denis; Rabasa-Lhoret, Rémi; Faraj, May

2014-01-01

We previously reported the secretion of apolipoprotein apoC-I, apoC-II, apoC-III, and apoE from adipose tissue in postmenopausal obese women, suggesting their potential regulation by energy balance in humans. We examined the changes of these apolipoproteins, in relation to changes in cardiometabolic risks, following a hypocaloric diet in overweight/obese women. A total of 137 postmenopausal overweight/obese women who were free of chronic disease were examined at baseline, 56 women of whom were reevaluated following a 6-month hypocaloric diet. At baseline, there was no association between the plasma transferable apolipoproteins with any index of adiposity, insulin sensitivity, lipids, or inflammation, except for apoE with peripheral fat mass (r = 0.18, P hypocaloric diet reduced adiposity, insulin resistance, and inflammatory markers but had no significant effects on plasma transferable apolipoproteins or lipids, whose average concentrations were within normal range at baseline. The changes in total and central, but not peripheral, fat mass associated with changes of apoC-I only (r = 0.28 and r = 0.43; respectively, P < .05). Post-weight-loss apoC-I increased in some women (52%) yet it decreased in others, however there were no differences in cardiometabolic risk factors between the 2 groups. Plasma apoC-I, apoC-II, apoC-III, and apoE are not associated with adiposity, insulin sensitivity, or inflammation in obese but healthy postmenopausal women. Post-weight-loss changes of total and central fat mass associate with changes of apoC-I. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Influence of apolipoproteins on the association between lipids and insulin sensitivity

DEFF Research Database (Denmark)

Baldi, Simona; Bonnet, Fabrice; Laville, Martine

2013-01-01

We evaluated whether the association of insulin sensitivity with HDL cholesterol (HDL) and triglycerides is influenced by major plasma apolipoproteins, as suggested by recent experimental evidence....

Human placenta secretes apolipoprotein B-100-containing lipoproteins

DEFF Research Database (Denmark)

Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B

2004-01-01

Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... of lipid transfer from the mother to the developing fetus....

Reduced apolipoprotein glycosylation in patients with the metabolic syndrome.

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Olga V Savinova

Full Text Available The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls.Very low density (VLDL, intermediate/low density (IDL/LDL, hereafter LDL, and high density lipoproteins (HDL fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays.Metabolic syndrome patients differed from healthy controls in the following ways: (1 total plasma--apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2 VLDL--apoB, apoC3, and apoE were increased; (3 LDL--apoC3 was increased, (4 HDL--associated constitutive serum amyloid A protein (SAA4 was reduced (p<0.05 vs. controls for all. In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all. Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all. Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001.Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.

Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand-Bound Copper(I).

Science.gov (United States)

Hanna, Jill R; Allan, Christopher; Lawrence, Charlotte; Meyer, Odile; Wilson, Neil D; Hulme, Alison N

2017-05-14

The CuAAC 'click' reaction was used to couple alkyne-functionalized lanthanide-DOTA complexes to a range of fluorescent antennae. Screening of the antenna components was aided by comparison of the luminescent output of the resultant sensors using data normalized to account for reaction conversion as assessed by IR. A maximum 82-fold enhanced signal:background luminescence output was achieved using a Eu(III)-DOTA complex coupled to a coumarin-azide, in a reaction which is specific to the presence of copper(I). This optimized complex provides a new lead design for lanthanide-DOTA complexes which can act as irreversible 'turn-on' catalytic sensors for the detection of ligand-bound copper(I).

Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand-Bound Copper(I

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Jill R. Hanna

2017-05-01

Full Text Available The CuAAC ‘click’ reaction was used to couple alkyne-functionalized lanthanide-DOTA complexes to a range of fluorescent antennae. Screening of the antenna components was aided by comparison of the luminescent output of the resultant sensors using data normalized to account for reaction conversion as assessed by IR. A maximum 82-fold enhanced signal:background luminescence output was achieved using a Eu(III-DOTA complex coupled to a coumarin-azide, in a reaction which is specific to the presence of copper(I. This optimized complex provides a new lead design for lanthanide-DOTA complexes which can act as irreversible ‘turn-on’ catalytic sensors for the detection of ligand-bound copper(I.

Lipoproteins of slow-growing Mycobacteria carry three fatty acids and are N-acylated by apolipoprotein N-acyltransferase BCG_2070c.

Science.gov (United States)

Brülle, Juliane K; Tschumi, Andreas; Sander, Peter

2013-10-05

Lipoproteins are virulence factors of Mycobacterium tuberculosis. Bacterial lipoproteins are modified by the consecutive action of preprolipoprotein diacylglyceryl transferase (Lgt), prolipoprotein signal peptidase (LspA) and apolipoprotein N- acyltransferase (Lnt) leading to the formation of mature triacylated lipoproteins. Lnt homologues are found in Gram-negative and high GC-rich Gram-positive, but not in low GC-rich Gram-positive bacteria, although N-acylation is observed. In fast-growing Mycobacterium smegmatis, the molecular structure of the lipid modification of lipoproteins was resolved recently as a diacylglyceryl residue carrying ester-bound palmitic acid and ester-bound tuberculostearic acid and an additional amide-bound palmitic acid. We exploit the vaccine strain Mycobacterium bovis BCG as model organism to investigate lipoprotein modifications in slow-growing mycobacteria. Using Escherichia coli Lnt as a query in BLASTp search, we identified BCG_2070c and BCG_2279c as putative lnt genes in M. bovis BCG. Lipoproteins LprF, LpqH, LpqL and LppX were expressed in M. bovis BCG and BCG_2070c lnt knock-out mutant and lipid modifications were analyzed at molecular level by matrix-assisted laser desorption ionization time-of-flight/time-of-flight analysis. Lipoprotein N-acylation was observed in wildtype but not in BCG_2070c mutants. Lipoprotein N- acylation with palmitoyl and tuberculostearyl residues was observed. Lipoproteins are triacylated in slow-growing mycobacteria. BCG_2070c encodes a functional Lnt in M. bovis BCG. We identified mycobacteria-specific tuberculostearic acid as further substrate for N-acylation in slow-growing mycobacteria.

Effects of red grape juice consumption on high density lipoprotein-cholesterol, apolipoprotein AI, apolipoprotein B and homocysteine in healthy human volunteers.

Science.gov (United States)

Khadem-Ansari, Mohammad H; Rasmi, Yousef; Ramezani, Fatemeh

2010-01-01

It has suggested that grape juice consumption has lipid- lowering effect and it is associated with a decreased risk of heart disease. We aimed to evaluate the effects of red grape juice (RGj) consumption on high density lipoprotein-cholesterol (HDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB) and homocysteine (Hcy) levels in healthy human volunteers. Twenty six healthy and nonsmoking males, aged between 25-60 years, who were under no medication asked to consume 150 ml of RGj twice per day for one month. Serum HDL-C, apoAI, apoB and plasma Hcy levels were measured before and after one month RGj consumption. HDL-C levels after RGj consumption were significantly higher than the corresponding levels before the RGj consumption (41.44 ± 4.50 and 44.37 ± 4.30 mg/dl; P0.05). Hcy levels were decreased after RGj consumption (7.70 ± 2.80 and 6.20 ± 2.30 µmol/l; P<0.001). The present study demonstrates that RGj consumption can significantly increase serum HDL-C levels and decrease Hcy levels. These findings may have important implications for the prevention of atherosclerosis in healthy individuals.

Can abnormal returns be earned on bandwidth-bounded currencies? Evidence from a genetic algorithm

OpenAIRE

Pedro Godinho

2012-01-01

Most of the studies about the Foreign Exchange market (Forex) analyse the behaviour of currencies that are allowed to float freely (or almost freely), but some currencies are still bounded by bandwidths (either disclosed or undisclosed). In this paper, I try to find out whether two bandwidth-bounded currencies, the Hong Kong dollar (HKD) and the Singapore dollar (SGD), present opportunities for abnormal returns. I consider a set of trading rules, and I use a genetic algorithm to optimise both...

Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones.

Science.gov (United States)

Zensi, Anja; Begley, David; Pontikis, Charles; Legros, Celine; Mihoreanu, Larisa; Wagner, Sylvia; Büchel, Claudia; von Briesen, Hagen; Kreuter, Jörg

2009-07-01

The blood-brain barrier (BBB) represents a considerable obstacle to brain entry of the majority of drugs and thus severely restricts the therapy of many serious CNS diseases including brain tumours, brain HIV, Alzheimer and other neurodegenerative diseases. The use of nanoparticles coated with polysorbate 80 or with attached apolipoprotein E has enabled the delivery of drugs across the BBB. However, the mechanism of this enhanced transport is still not fully understood. In this present study, human serum albumin nanoparticles, with covalently bound apolipoprotein E (Apo E) as a targetor as well as without apolipoprotein E, were manufactured and injected intravenously into SV 129 mice. The animals were sacrificed after 15 and 30 min, and their brains were examined by transmission electron microscopy. Only the nanoparticles with covalently bound apolipoprotein E were detected in brain capillary endothelial cells and neurones, whereas no uptake into the brain was detectable with nanoparticles without apolipoprotein E. We have also demonstrated uptake of the albumin/ApoE nanoparticles into mouse endothelial (b.End3) cells in vitro and their intracellular localisation. These findings indicate that nanoparticles with covalently bound apolipoprotein E are taken up into the cerebral endothelium by an endocytic mechanism followed by transcytosis into brain parenchyma.

Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

International Nuclear Information System (INIS)

Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

2004-01-01

Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

Energy Technology Data Exchange (ETDEWEB)

Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

2004-10-01

Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

Apolipoprotein e4 allele and cognitive decline in elderly men

NARCIS (Netherlands)

Feskens, E.J.M.; Havekes, L.M.; Kalmijn, S.; Knijff, P. de; Launer, L.J.; Kromhout, D.

1994-01-01

Objectives - To determine whether polymorphism of apolipoprotein E - notably, the e4 allele - predicts cognitive deterioration in the general population. Design - Population based cohort investigated in 1990 and in 1993. Setting - Zutphen, the Netherlands. Subjects - Representative cohort of 538

Improved Range Searching Lower Bounds

DEFF Research Database (Denmark)

Larsen, Kasper Green; Nguyen, Huy L.

2012-01-01

by constructing a hard input set and query set, and then invoking Chazelle and Rosenberg's [CGTA'96] general theorem on the complexity of navigation in the pointer machine. For the group model, we show that input sets and query sets that are hard for range reporting in the pointer machine (i.e. by Chazelle...... and Rosenberg's theorem), are also hard for dynamic range searching in the group model. This theorem allows us to reuse decades of research on range reporting lower bounds to immediately obtain a range of new group model lower bounds. Amongst others, this includes an improved lower bound for the fundamental...

Lower Bounds for External Memory Dictionaries

DEFF Research Database (Denmark)

Brodal, Gerth Stølting; Fagerberg, Rolf

2003-01-01

We study trade-offs between the update time and the query time for comparison based external memory dictionaries. The main contributions of this paper are two lower bound trade offs between the I/O complexity of member queries and insertions: If N < M insertions perform at most δ · N/B I/Os, then......We study trade-offs between the update time and the query time for comparison based external memory dictionaries. The main contributions of this paper are two lower bound trade offs between the I/O complexity of member queries and insertions: If N

An apolipoprotein A-V gene SNP is associated with marked hypertriglyceridemia among Asian-American patients

NARCIS (Netherlands)

C.R. Pullinger (Clive); B.E. Aouizerat (Bradley); I. Movsesyan (Irina); V. Durlach (Vincent); E.J.G. Sijbrands (Eric); K. Nakajima (Katsuyuki); A. Poon (Annie); G.M. Dallinga-Thie (Geesje); H. Hattori (Hiroaki); L.L. Green (Lauri); P.-Y. Kwok (Pui-Yan); R.J. Havel (Richard); P.H. Frost (Philip); M.J. Malloy (Mary); J.P. Kane (John)

2008-01-01

textabstractApolipoprotein A-V (apoA-V) is an important regulator of plasma levels of triglyceride (TG) in mice. In humans, APOA5 genetic variation is associated with TG in several populations. In this study, we determined the effects of the p.185Gly>Cys (c.553G>T; rs2075291) polymorphism on plasma

Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke

DEFF Research Database (Denmark)

Khan, Tauseef A; Shah, Tina; Prieto, David

2013-01-01

At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less c...

Host-derived apolipoproteins play comparable roles with viral secretory proteins Erns and NS1 in the infectious particle formation of Flaviviridae.

Directory of Open Access Journals (Sweden)

Takasuke Fukuhara

2017-06-01

Full Text Available Amphipathic α-helices of exchangeable apolipoproteins have shown to play crucial roles in the formation of infectious hepatitis C virus (HCV particles through the interaction with viral particles. Among the Flaviviridae members, pestivirus and flavivirus possess a viral structural protein Erns or a non-structural protein 1 (NS1 as secretory glycoproteins, respectively, while Hepacivirus including HCV has no secretory glycoprotein. In case of pestivirus replication, the C-terminal long amphipathic α-helices of Erns are important for anchoring to viral membrane. Here we show that host-derived apolipoproteins play functional roles similar to those of virally encoded Erns and NS1 in the formation of infectious particles. We examined whether Erns and NS1 could compensate for the role of apolipoproteins in particle formation of HCV in apolipoprotein B (ApoB and ApoE double-knockout Huh7 (BE-KO, and non-hepatic 293T cells. We found that exogenous expression of either Erns or NS1 rescued infectious particle formation of HCV in the BE-KO and 293T cells. In addition, expression of apolipoproteins or NS1 partially rescued the production of infectious pestivirus particles in cells upon electroporation with an Erns-deleted non-infectious RNA. As with exchangeable apolipoproteins, the C-terminal amphipathic α-helices of Erns play the functional roles in the formation of infectious HCV or pestivirus particles. These results strongly suggest that the host- and virus-derived secretory glycoproteins have overlapping roles in the viral life cycle of Flaviviridae, especially in the maturation of infectious particles, while Erns and NS1 also participate in replication complex formation and viral entry, respectively. Considering the abundant hepatic expression and liver-specific propagation of these apolipoproteins, HCV might have evolved to utilize them in the formation of infectious particles through deletion of a secretory viral glycoprotein gene.

Apolipoprotein A-IV inhibits AgRP/NPY neurons and activates POMC neurons in the arcuate nucleus

Science.gov (United States)

Apolipoprotein A-IV (apoA-IV) in the brain potently suppresses food intake. However the mechanisms underlying its anorexigenic effects remain to be identified. We first examined the effects of apoA-IV on cellular activities in hypothalamic neurons that co-express agouti-related peptide (AgRP) and ne...

Apolipoprotein E*3-Leiden transgenic mice mode for hypolipidaemic drugs

NARCIS (Netherlands)

Vlijmen, B.J.M. van; Pearce, N.J.; Bergö, M.; Staels, B.; Yates, J.W.; Gribble, A.D.; Bond, B.C.; Hofker, M.H.; Havekes, L.M.; Groot, P.H.E.

1998-01-01

Apolipoprotein (APO) E*3-Leiden mice with impaired chylomicron and VLDL (very low density lipoprotein) remnant metabolism display hyperlipidaemia and atherosclerosis. In the present study, these mice were used for testing the hypolipidaemic effect of two marketed agents, lovastatin (CAS 75330-75-5)

An apolipoprotein A-V gene SNP is associated with marked hypertriglyceridemia among Asian-American patients

NARCIS (Netherlands)

Pullinger, Clive R.; Aouizerat, Bradley E.; Movsesyan, Irina; Durlach, Vincent; Sijbrands, Eric J.; Nakajima, Katsuyuki; Poon, Annie; Dallinga-Thie, Geesje M.; Hattori, Hiroaki; Green, Lauri L.; Kwok, Pui-Yan; Havel, Richard J.; Frost, Philip H.; Malloy, Mary J.; Kane, John P.

2008-01-01

Apolipoprotein A-V (apoA-V) is an important regulator of plasma levels of triglyceride (TG) in mice. In humans, APOA5 genetic variation is associated with TG in several populations. In this study, we determined the effects of the p.185Gly>Cys (c.553G>T; rs2075291) polymorphism on plasma TG levels in

The common polymorphism of apolipoprotein E

DEFF Research Database (Denmark)

Gerdes, Ulrik

2003-01-01

from only 10-15% in southern Europe to 40-50% in the north. The gradient may be a trace of the demic expansion of agriculture that began about 10,000 years ago, but it may also reflect the possibility that APOE*4 carriers are less likely to develop vitamin D deficiency. The common APOE polymorphism......Apolipoprotein E (apoE) has important functions in systemic and local lipid transport, but also has other functions. The gene (APOE) shows a common polymorphism with three alleles--APOE*2, APOE*3, and APOE*4. Their frequencies vary substantially around the world, but APOE*3 is the most common...

Dynamics of bleomycin interaction with a strongly bound hairpin DNA substrate, and implications for cleavage of the bound DNA.

Science.gov (United States)

Bozeman, Trevor C; Nanjunda, Rupesh; Tang, Chenhong; Liu, Yang; Segerman, Zachary J; Zaleski, Paul A; Wilson, W David; Hecht, Sidney M

2012-10-31

Recent studies involving DNAs bound strongly by bleomycins have documented that such DNAs are degraded by the antitumor antibiotic with characteristics different from those observed when studying the cleavage of randomly chosen DNAs in the presence of excess Fe·BLM. In the present study, surface plasmon resonance has been used to characterize the dynamics of BLM B(2) binding to a strongly bound hairpin DNA, to define the effects of Fe(3+), salt, and temperature on BLM-DNA interaction. One strong primary DNA binding site, and at least one much weaker site, were documented. In contrast, more than one strong cleavage site was found, an observation also made for two other hairpin DNAs. Evidence is presented for BLM equilibration between the stronger and weaker binding sites in a way that renders BLM unavailable to other, less strongly bound DNAs. Thus, enhanced binding to a given site does not necessarily result in increased DNA degradation at that site; i.e., for strongly bound DNAs, the facility of DNA cleavage must involve other parameters in addition to the intrinsic rate of C-4' H atom abstraction from DNA sugars.

In vivo assessment of a novel dacron surface with covalently bound recombinant hirudin.

Science.gov (United States)

Wyers, M C; Phaneuf, M D; Rzucidlo, E M; Contreras, M A; LoGerfo, F W; Quist, W C

1999-01-01

Prosthetic arterial graft surfaces are relatively thrombogenic and fail to heal with a cellular neointima. The goal of this study was to characterize the in vivo antithrombin properties of a novel Dacron surface with covalently linked recombinant hirudin (rHir) implanted in a canine thoracic aorta with high flow and shear rates. rHir was bound to a knitted Dacron patch using crosslinker-modified bovine serum albumin (BSA) as a basecoat protein. BSA was first reacted with the heterobifunctional crosslinker, sulfo-SMCC. This BSA-SMCC complex was then bound to the carboxylic acid groups of hydrolyzed Dacron patches using the carbodiimide crosslinker, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. Iodinated, Traut's-modified rHir (125I-rHir-SH) was then reacted with the Dacron-BSA-SMCC surface, thereby covalently binding 125I-rHir. Graft segments were washed and sonicated to remove any nonspecifically bound 125I-rHir. Dacron-BSA-SMCC-S-125I-rHir patches (n = 5) and control Dacron-BSA patches (n = 5) were implanted in series in the thoracic aortas of canines. These patches were exposed to nonheparinized, arterial blood flow for 2 hours. Patches were explanted and assessed for 125I-rHir loss. Antithrombin activity of explanted 1-cm2 patch segments was evaluated using a chromogenic assay with 1, 5, 10, 15 units of added thrombin. Light microscopy was performed to qualitatively examine the pseudointima. Two animals were excluded from the study owing to excessive bleeding through the knitted 125I-rHir patch. Comparison of preoperative and postoperative 125I-rHir gamma counts revealed an overall decrease of 20+/-5.4% over the period studied. Explanted 125I-rHir patch segments were able to inhibit 1, 5, and 7 NIHU of thrombin, demonstrating retained antithrombin activity. Gross and microscopic examination of the control and test Dacron surfaces showed marked differences. Dacron surfaces with covalently bound 125I-rHir had no gross thrombus and a thin

Vulnerable Derivatives and Good Deal Bounds: A Structural Model

DEFF Research Database (Denmark)

Murgoci, Agatha

2013-01-01

We price vulnerable derivatives -- i.e. derivatives where the counterparty may default. These are basically the derivatives traded on the over-the-counter (OTC) markets. Default is modeled in a structural framework. The technique employed for pricing is good deal bounds (GDBs). The method imposes...

The-1131T > C Polymorphism in the Apolipoprotein A5 Gene is Related to Hypertriglyceridemia in Taiwanese Aborigines

Directory of Open Access Journals (Sweden)

Meng-Chuan Huang

2008-04-01

Full Text Available The prevalence of hypertriglyceridemia, considered to be an independent risk factor for the development of cardiovascular disease, is high in Taiwanese aborigines. This study was undertaken to examine the effect of the -1131T > C polymorphism in the apolipoprotein A5 gene on serum triglyceride levels in female Taiwanese aborigines. This was a cross-sectional study, and a total of 316 unrelated female Taiwanese aborigines were genotyped at the -1131T > C polymorphism in apolipoprotein A5 using the polymerase chain reaction-restriction fragment length polymorphism method. Serum triglyceride ≥150 mg/dL was defined as the hypertriglyceridemia group and triglyceride C polymorphism of the Apo A5 gene influences serum triglyceride levels in female Taiwanese aborigines, and that differences exist in the frequency of the C allele among people of various ethnicities.

Molecular Characterization and Growth Association of Two Apolipoprotein A-Ib Genes in Common Carp (Cyprinus carpio).

Science.gov (United States)

Wang, Xinhua; Yu, Xiaomu; Tong, Jingou

2016-09-16

Apolipoprotein A-I (ApoA-I) is functionally involved in the transportation and metabolism of lipids in vertebrates. In this study, two isoforms of apoA-Ib in common carp (Cyprinus carpio L.) were characterized. Sequence comparison and phylogenetic analysis showed that C. carpio ApoA-Ib is relatively conserved within cyprinid fishes. During embryonic development, C. carpio apoA-Ib was first expressed at the stage of multi-cells, and the highest mRNA level was observed at the stage of optic vesicle. A ubiquitous expression pattern was detected in various tissues with extreme predominance in the liver. Significantly different expression levels were observed between light and heavy body weight groups and also in the compensatory growth test. Seventeen and eight single-nucleotide polymorphisms (SNPs) were identified in matured mRNA of the C. carpio apoA-Ib.1 and apoA-Ib.2, respectively. Two of these SNPs (apoA-Ib.2-g.183A>T and apoA-Ib.2-g.1753C>T) were significantly associated with body weight and body length in two populations of common carp. These results indicate that apoA-Ib may play an important role in the modulation of growth and development in common carp.

A linear programming approach to characterizing norm bounded uncertainty from experimental data

Science.gov (United States)

Scheid, R. E.; Bayard, D. S.; Yam, Y.

1991-01-01

The linear programming spectral overbounding and factorization (LPSOF) algorithm, an algorithm for finding a minimum phase transfer function of specified order whose magnitude tightly overbounds a specified nonparametric function of frequency, is introduced. This method has direct application to transforming nonparametric uncertainty bounds (available from system identification experiments) into parametric representations required for modern robust control design software (i.e., a minimum-phase transfer function multiplied by a norm-bounded perturbation).

Apolipoprotein C3 polymorphism is associated with cognitive function in Caribbean Hispanics

Science.gov (United States)

Background: Apolipoprotein C3(APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired ...

The age dependency of gene expression for plasma lipids, lipoproteins, and apolipoproteins

Energy Technology Data Exchange (ETDEWEB)

Snieder, H.; Doornen, L.J.P. van; Boomsma, D.I. [Vrije Universiteit, Amsterdam (Netherlands)

1997-03-01

The aim of this study was to investigate and disentangle the genetic and nongenetic causes of stability and change in lipids and (apo)lipoproteins that occur during the lifespan. Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) were measured in a group of 160 middle-aged parents and their twin offspring (first project) and in a group of 203 middle-aged twin pairs (second project). Combining the data of both projects enabled the estimation of the extent to which measured lipid parameters are influenced by different genes in adolescence and adulthood. To that end, an extended quantitative genetic model was specified, which allowed the estimation of heritabilities for each sex and generation separately. Heritabilities were similar for both sexes and both generations. Larger variances in the parental generation could be ascribed to proportional increases in both unique environmental and additive genetic variance from childhood to adulthood, which led to similar heritability estimates in adolescent and middle-aged twins. Although the magnitudes of heritabilities were similar across generations, results showed that, for total cholesterol, triglycerides, HDL, and LDL, partly different genes are expressed in adolescence compared to adulthood. For triglycerides, only 46% of the genetic variance was common to both age groups; for total cholesterol this was 80%. Intermediate values were found for HDL (66%) and LDL (76%). For ApoA1, ApoB, and Lp(a), the same genes seem to act in both generations. 56 refs., 2 figs., 5 tabs.

Expression of apolipoprotein B in the kidney attenuates renal lipid accumulation

DEFF Research Database (Denmark)

Krzystanek, Marcin; Pedersen, Tanja Xenia; Bartels, Emil Daniel

2010-01-01

The ability to produce apolipoprotein (apo) B-containing lipoproteins enables hepatocytes, enterocytes, and cardiomyocytes to export triglycerides. In this study, we examined secretion of apoB-containing lipoproteins from mouse kidney and its putative impact on triglyceride accumulation in the tu...

Clinical application of human serum apolipoprotein B ria

International Nuclear Information System (INIS)

He Rongxia

1988-01-01

The serum apolipoprotein B (Apo B) was measured in 89 normal subjects with radioimmunoassay method established by the authors, among them 50 patients with coronary heart disease (CHD), 19 patients with cerebrae-vascular accident (CVA) and 46 patients with hyperlipemia. Meanwhile the serum cholesterol and triglyceride were also measured. Although cholesterol, triglyceride, and Apo B levels in disease groups were all significantly higher than control group, there are more overlap between the control and disease group for cholesterol and triglyceride. The Apo B level was 723.9 +- 195.9 mg/L in control group, 1097 +- 236.0 mg/L in CHD group and in CVA group, and this difference was highly significant (P < 0.001). Besides, less overlap of the Apo B value between disease and countrol group was observed in both disease groups. When the Apo B was used as single parameter for the diagnosis CHD, the accuracy rate reached 82%. The results of this study indicated that measurement of Apo B can offer important prediction for coronary artery disease, especially in those having normal levels of plasma cholesterol. In conclusion, the study of apolipoprotein is more significant than lipid component in discriminating between atherosclerotic patients and normal persons

Is Apolipoprotein E4 an Important Risk Factor for Dementia in Persons with Down Syndrome?

Science.gov (United States)

Rohn, Troy T; McCarty, Katie L; Love, Julia E; Head, Elizabeth

2014-12-08

Down syndrome is one of the most common genetic causes of intellectual disability and is characterized by a number of behavioral as well as cognitive symptoms. Triplication of all or part of human chromosome 21 has been considered as the main cause of Down syndrome. Due to the location of the amyloid precursor protein on chromosome 21, many of the neuropathological features of early-onset Alzheimer's disease including senile plaques and neurofibrillary tangles are also present in Down syndrome patients who are either demented or nondemented. Significant advances in medical treatment have increased longevity in people with Down syndrome resulting in an increased population that may be subjected to many of the same risk factors as those with Alzheimer's disease. It is well established that harboring one or both apolipoprotein E4 alleles greatly increases the risk for Alzheimer's disease. However, whether apolipoprotein E4 contributes to an earlier onset of dementia or increased mortality in Down syndrome patients is still a matter of debate. The purpose of this mini review is to provide an updated assessment on apolipoprotein E4 status and risk potential of developing dementia and mortality associated with Down syndrome.

Apolipoprotein D is associated with long-term outcome in patients with schizophrenia

DEFF Research Database (Denmark)

Hansen, T; Hemmingsen, R P; Wang, A G

2006-01-01

Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second, gene......D alleles, genotypes or haplotypes to be associated with disease. However, we did find that long-term clinical outcome was associated with the ApoD polymorphism rs7659 (P = 0.041) following adjustment for lifetime clinical global impression, age at first admission and gender.......Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second...

Establishing the existence of a distance-based upper bound for a fuzzy DEA model using duality

International Nuclear Information System (INIS)

Soleimani-damaneh, M.

2009-01-01

In a recent paper [Soleimani-damaneh M. Fuzzy upper bounds and their applications. Chaos, Solitons and Fractals 2008;36:217-25.], I established the existence of a distance-based fuzzy upper bound for the objective function of a fuzzy DEA model, using the properties of a discussed signed distance, and provided an effective approach to solve that model. In this paper a new dual-based proof for the existence of the above-mentioned upper bound is provided which gives a useful insight into the theory of fuzzy DEA.

Lipid, lipoprotein, and apolipoprotein profiles in active and sedentary men with tetraplegia

NARCIS (Netherlands)

Dallmeijer, A J; Hopman, M T; van der Woude, L H

1997-01-01

OBJECTIVE: To investigate whether the risk profile of coronary heart disease (CHD) is more favorable in physically active men with tetraplegia compared with sedentary men with tetraplegia. DESIGN: Using a cross-sectional design, the lipid and (apo)lipoprotein concentrations of 11 active and 13

Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism

NARCIS (Netherlands)

Helgadottir, Anna; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Holm, Hilma; Patel, Riyaz S.; Gudnason, Thorarinn; Jones, Gregory T.; van Rij, Andre M.; Eapen, Danny J.; Baas, Annette F.; Tregouet, David-Alexandre; Morange, Pierre-Emmanuel; Emmerich, Joseph; Lindblad, Bengt; Gottsater, Anders; Kiemeny, Lambertus A.; Lindholt, Jes S.; Sakalihasan, Natzi; Ferrell, Robert E.; Carey, David J.; Elmore, James R.; Tsao, Philip S.; Grarup, Niels; Jorgensen, Torben; Witte, Daniel R.; Hansen, Torben; Pedersen, Oluf; Pola, Roberto; Gaetani, Eleonora; Magnadottir, Hulda B.; Wijmenga, Cisca; Tromp, Gerard; Ronkainen, Antti; Ruigrok, Ynte M.; Blankensteijn, Jan D.; Mueller, Thomas; Wells, Philip S.; Corral, Javier; Manuel Soria, Jose; Carlos Souto, Juan; Peden, John F.; Jalilzadeh, Shapour; Mayosi, Bongani M.; Keavney, Bernard; Strawbridge, Rona J.; Sabater-Lleal, Maria; Gertow, Karl; Baldassarre, Damiano; Nyyssonen, Kristiina; Rauramaa, Rainer; Smit, Andries J.; Mannarino, Elmo; Giral, Philippe; Tremoli, Elena; de Faire, Ulf; Humphries, Steve E.; Hamsten, Anders; Haraldsdottir, Vilhelmina; Olafsson, Isleifur; Magnusson, Magnus K.; Samani, Nilesh J.; Levey, Allan I.; Markus, Hugh S.; Kostulas, Konstantinos; Dichgans, Martin; Berger, Klaus; Kuhlenbaeumer, Gregor; Ringelstein, E. Bernd; Stoll, Monika; Seedorf, Udo; Rothwell, Peter M.; Powell, Janet T.; Kuivaniemi, Helena; Onundarson, Pall T.; Valdimarsson, Einar; Matthiasson, Stefan E.; Gudbjartsson, Daniel F.; Thorgeirsson, Guomundur; Quyyumi, Arshed A.; Watkins, Hugh; Farrall, Martin; Thorsteinsdottir, Unnur; Stefansson, Kari

2012-01-01

Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with

Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake

NARCIS (Netherlands)

Berg, S.A.A. van den; Heemskerk, M.M.; Geerling, J.J.; Klinken, J.B. van; Schaap, F.G.; Bijland, S.; Berbée, J.F.P.; Harmelen, V.J.A. van; Pronk, A.C.M.; Schreurs, M.; Havekes, L.M.; Rensen, P.C.N.; Dijk, K.W. van

2013-01-01

Mutations in apolipoprotein A5 (APOA5) have been associated with hypertriglyceridemia in humans and mice. This has been attributed to a stimulating role for APOA5 in lipoprotein lipase-mediated triglyceride hydrolysis and hepatic clearance of lipoprotein remnant particles. However, because of the

Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake

NARCIS (Netherlands)

van den Berg, Sjoerd A. A.; Heemskerk, Mattijs M.; Geerling, Janine J.; van Klinken, Jan-Bert; Schaap, Frank G.; Bijland, Silvia; Berbee, Jimmy F. P.; van Harmelen, Vanessa J. A.; Pronk, Amanda C. M.; Bijker-Schreurs, Marijke; Havekes, Louis M.; Rensen, Patrick C. N.; van Dijk, Ko Willems

Mutations in apolipoprotein A5 (APOA5) have been associated with hypertriglyceridemia in humans and mice. This has been attributed to a stimulating role for APOA5 in lipoprotein lipase-mediated triglyceride hydrolysis and hepatic clearance of lipoprotein remnant particles. However, because of the

Human placenta secretes apolipoprotein B-100-containing lipoproteins

DEFF Research Database (Denmark)

Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B

2004-01-01

Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... lipoproteins secreted from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm. These results demonstrate that human placenta expresses both apoB and MTP and consequently synthesize and secrete apoB-100-containing lipoproteins. Placental lipoprotein formation constitutes a novel pathway...

Extrinsic Isoperimetric Analysis on Submanifolds with Curvatures bounded from below

DEFF Research Database (Denmark)

Markvorsen, Steen; Palmer, Vicente

2010-01-01

and on the radial part of the intrinsic unit normals at the boundaries of the extrinsic spheres, respectively. In the same vein we also establish lower bounds on the mean exit time for Brownian motions in the extrinsic balls, i.e. lower bounds for the time it takes (on average) for Brownian particles to diffuse......We obtain upper bounds for the isoperimetric quotients of extrinsic balls of submanifolds in ambient spaces which have a lower bound on their radial sectional curvatures. The submanifolds are themselves only assumed to have lower bounds on the radial part of the mean curvature vector field...... within the extrinsic ball from a given starting point before they hit the boundary of the extrinsic ball. In those cases, where we may extend our analysis to hold all the way to infinity, we apply a capacity comparison technique to obtain a sufficient condition for the submanifolds to be parabolic, i...

Effect of Bound Entanglement on the Convertibility of Pure States

International Nuclear Information System (INIS)

Ishizaka, Satoshi

2004-01-01

I show that bound entanglement strongly influences the quantum entanglement processing of pure states: If N distant parties share appropriate bound entangled states with positive partial transpose, all N-partite pure entangled states become inter-convertible by stochastic local operations and classical communication (SLOCC) at the single copy level. This implies that the Schmidt rank of a bipartite pure entangled state can be increased, and that two incomparable tripartite entanglement of the GHZ and W type can be inter-converted by the assistance of bound entanglement. Further, I propose the simplest experimental scheme for the demonstration of the corresponding bound-entanglement-assisted SLOCC. This scheme does not need quantum gates and is feasible for the current experimental technology of linear optics

A symmetric Roos bound for linear codes

NARCIS (Netherlands)

Duursma, I.M.; Pellikaan, G.R.

2006-01-01

The van Lint–Wilson AB-method yields a short proof of the Roos bound for the minimum distance of a cyclic code. We use the AB-method to obtain a different bound for the weights of a linear code. In contrast to the Roos bound, the role of the codes A and B in our bound is symmetric. We use the bound

Models and Techniques for Proving Data Structure Lower Bounds

DEFF Research Database (Denmark)

Larsen, Kasper Green

In this dissertation, we present a number of new techniques and tools for proving lower bounds on the operational time of data structures. These techniques provide new lines of attack for proving lower bounds in both the cell probe model, the group model, the pointer machine model and the I...... bound of tutq = (lgd􀀀1 n). For ball range searching, we get a lower bound of tutq = (n1􀀀1=d). The highest previous lower bound proved in the group model does not exceed ((lg n= lg lg n)2) on the maximum of tu and tq. Finally, we present a new technique for proving lower bounds....../O-model. In all cases, we push the frontiers further by proving lower bounds higher than what could possibly be proved using previously known techniques. For the cell probe model, our results have the following consequences: The rst (lg n) query time lower bound for linear space static data structures...

Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice

Czech Academy of Sciences Publication Activity Database

Dolejší, Eva; Liraz, O.; Rudajev, Vladimír; Zimčík, Pavel; Doležal, Vladimír; Michaelson, D. M.

2016-01-01

Roč. 136, č. 3 (2016), s. 503-509 ISSN 0022-3042 R&D Projects: GA MŠk(CZ) LH13269 Institutional support: RVO:67985823 Keywords : acetylcholine release * Alzheimer's disease (AD) * apolipoprotein E4 (apoE4) * hippocampus Subject RIV: FH - Neurology Impact factor: 4.083, year: 2016

Generalized bounds for convex multistage stochastic programs

CERN Document Server

Künzi, H; Fandel, G; Trockel, W; Basile, A; Drexl, A; Dawid, H; Inderfurth, K; Kürsten, W; Schittko, U

2005-01-01

This work was completed during my tenure as a scientific assistant and d- toral student at the Institute for Operations Research at the University of St. Gallen. During that time, I was involved in several industry projects in the field of power management, on the occasion of which I was repeatedly c- fronted with complex decision problems under uncertainty. Although usually hard to solve, I quickly learned to appreciate the benefit of stochastic progr- ming models and developed a strong interest in their theoretical properties. Motivated both by practical questions and theoretical concerns, I became p- ticularly interested in the art of finding tight bounds on the optimal value of a given model. The present work attempts to make a contribution to this important branch of stochastic optimization theory. In particular, it aims at extending some classical bounding methods to broader problem classes of practical relevance. This book was accepted as a doctoral thesis by the University of St. Gallen in June 2004.1...

Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B

DEFF Research Database (Denmark)

Benn, Marianne; Nordestgaard, Børge G; Jensen, Gorm Boje

2007-01-01

Apolipoprotein B (apoB) levels predict fatal myocardial infarction. Whether apoB also predicts nonfatal ischemic cardiovascular events is unclear. We tested the following hypotheses: apoB predicts ischemic cardiovascular events, and apoB is a better predictor of ischemic cardiovascular events tha...

Apolipoprotein CIII polymorphism and triglyceride levels of a Japanese population living in Southern Brazil

Directory of Open Access Journals (Sweden)

L. Parzianello

2008-06-01

Full Text Available Apolipoprotein CIII (apo-CIII participates in the regulation of triglyceride-rich lipoprotein metabolism. Several polymorphic sites have been detected within and around the apo-CIII gene. Here, we examined the relationship between apo-CIII SstI polymorphism (CC, CG, GG genotypes and plasma triglyceride (TG levels in a group of 159 Japanese individuals living in Southern Brazil. The sample was divided into a group of Japanese descendants (N = 51 with high TG (HTG; >200 mg/dL and a group of Japanese descendants (N = 108 with normal TG (NTG; <200 mg/dL. TG and total cholesterol levels were analyzed by an enzymatic method using the Labtest-Diagnostic kit and high- and low-density lipoproteins by a direct method using the Labtest-Diagnostic kit and DiaSys Diagnostic System International kit, respectively. A 428-bp sequence of apo-CIII gene was amplified using oligonucleotide primers 5' GGT GAC CGA TGG CTT CAG TTC CCT GA 3' and 5' CAG AAG GTG GAT AGA GCG CTG GCC T 3'. The PCR products were digested with a restriction endonuclease SstI. Rare G allele was highly prevalent in our study population (0.416 compared to Caucasians (0.00-0.11. G allele was almost two times more prevalent in the HTG group compared to the NTG group (P < 0.001. The genotype distribution was consistent with the Hardy-Weinberg equilibrium. There was a significant association between rare G allele and HTG in Japanese individuals living in Southern Brazil as indicated by one-way ANOVA, P < 0.05.

Tight bounds on the size of neural networks for classification problems

Energy Technology Data Exchange (ETDEWEB)

Beiu, V. [Los Alamos National Lab., NM (United States); Pauw, T. de [Universite Catholique de Louvain, Louvain-la-Neuve (Belgium). Dept. de Mathematique

1997-06-01

This paper relies on the entropy of a data-set (i.e., number-of-bits) to prove tight bounds on the size of neural networks solving a classification problem. First, based on a sequence of geometrical steps, the authors constructively compute an upper bound of O(mn) on the number-of-bits for a given data-set - here m is the number of examples and n is the number of dimensions (i.e., R{sup n}). This result is used further in a nonconstructive way to bound the size of neural networks which correctly classify that data-set.

A Lagrangian lower bound for the container transshipment problem at a railway hub for a fast branch-and-bound algorithm

OpenAIRE

M Barketau; H Kopfer; E Pesch

2013-01-01

In this paper, we consider the container transshipment problem at a railway hub. A simple lower bound known for this problem will be improved by a new Lagrangian relaxation lower bound. Computational tests show that this lower bound outperforms the simple one and decreases substantially the run time of the branch-and-bound algorithm.

Protection from obesity and insulin resistance in mice overexpressing human apolipoprotein C1

NARCIS (Netherlands)

Jong, M. C.; Voshol, P. J.; Muurling, M.; Dahlmans, V. E.; Romijn, J. A.; Pijl, H.; Havekes, L. M.

2001-01-01

Apolipoprotein (APO) C1 is a 6.6-kDa protein present in plasma and associated with lipoproteins. Using hyperinsulinemic-euglycemic clamp tests, we previously found that in APOC1 transgenic mice, the whole-body insulin-mediated glucose uptake is increased concomitant with a decreased fatty acid

Measurement of apolipoprotein B radioactivity in whole blood plasma by precipitation with isopropanol

International Nuclear Information System (INIS)

Yamada, N.; Havel, R.J.

1986-01-01

A method to measure apolipoprotein B radioactivity in whole blood plasma is described that is suitable for routine use in kinetic experiments in vivo. Radiolabeled apolipoprotein B is precipitated from plasma diluted 15- to 30-fold in the presence of carrier low density lipoproteins by 50% isopropanol. The amount of radioiodine in apoB is estimated from the difference between total radioiodine concentration in whole plasma and the fraction soluble in 50% isopropanol. Addition of up to 100 microliters of plasma to radioiodinated lipoproteins did not alter the percent of radioiodine precipitated in 1500 microliters of 50% isopropanol. The percent of radioiodine precipitated by isopropanol 3 min after intravenous injection of homologous radioiodinated very low density lipoproteins, intermediate density lipoproteins, and low density lipoproteins into rabbits was almost identical to that in the injected lipoproteins (y = 1.009 X +/- 0.462; r = 0.997)

Reduced conservatism in stability robustness bounds by state transformation

Science.gov (United States)

Yedavalli, R. K.; Liang, Z.

1986-01-01

This note addresses the issue of 'conservatism' in the time domain stability robustness bounds obtained by the Liapunov approach. A state transformation is employed to improve the upper bounds on the linear time-varying perturbation of an asymptotically stable linear time-invariant system for robust stability. This improvement is due to the variance of the conservatism of the Liapunov approach with respect to the basis of the vector space in which the Liapunov function is constructed. Improved bounds are obtained, using a transformation, on elemental and vector norms of perturbations (i.e., structured perturbations) as well as on a matrix norm of perturbations (i.e., unstructured perturbations). For the case of a diagonal transformation, an algorithm is proposed to find the 'optimal' transformation. Several examples are presented to illustrate the proposed analysis.

Altered plasma apolipoprotein modifications in patients with pancreatic cancer: protein characterization and multi-institutional validation.

Directory of Open Access Journals (Sweden)

Kazufumi Honda

Full Text Available BACKGROUND: Among the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection. METHODS: We compared the plasma protein profiles of 112 pancreatic cancer patients with those of 103 sex- and age-matched healthy controls (Cohort 1 using a newly developed matrix-assisted laser desorption/ionization (oMALDI QqTOF (quadrupole time-of-flight mass spectrometry (MS system. RESULTS: We found that hemi-truncated apolipoprotein AII dimer (ApoAII-2; 17252 m/z, unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 m/z, and their summed value were significantly decreased in the pancreatic cancer patients [P = 1.36×10(-21, P = 4.35×10(-14, and P = 1.83×10(-24 (Mann-Whitney U-test; area-under-curve values of 0.877, 0.798, and 0.903, respectively]. The significance was further validated in a total of 1099 plasma/serum samples, consisting of 2 retrospective cohorts [Cohort 2 (n = 103 and Cohort 3 (n = 163] and a prospective cohort [Cohort 4 (n = 833] collected from 8 medical institutions in Japan and Germany. CONCLUSIONS: We have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.

Apolipoprotein D is associated with long-term outcome in patients with schizophrenia

DEFF Research Database (Denmark)

Hansen, Thomas Folkmann; Hemmingsen, R P; Wang, A G

2006-01-01

Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second, gene...

Comparison of Serum Apolipoprotein Levels of Diabetic Children and Healthy Children with or without Diabetic Parents

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Mohammad Hashemi

2012-01-01

Full Text Available Introduction. The association of diabetes and atherosclerosis with disorders of lipids and lipoproteins, notably high apolipoprotein B (apoB and low apolipoprotein A1(apoA1 is well established. Because of the beginning of the atherosclerosis' process from early life, in this study, the plasma levels of apoA1 and apoB were compared in diabetic children with type I diabetes mellitus(DM, healthy children with diabetic parents (HDPs,and healthy children with nondiabetic parents (HNDPs. Methods. This case-control study was conducted among 90 children aged 9–18 years. Serum levels of apoA and apoB were compared among 30 diabetic children (DM, 30 healthy children with diabetic parents (HDPs, and 30 healthy children with nondiabetic parents (HNDP. Results. The mean serum apoA1 was higher in DM (153±69 mg/dL followed by HNDPs (138±58 mg/dL and HDPs (128±56 mg/dl, but the difference was not statistically significant. The mean apoB value in HNDPs was significantly lower than DM and HDPs (90±21 mg/dL versus 127±47 and 128±38 mg/dL, P0.05. Conclusions. Diabetic children and healthy children with diabetic parent(s are at higher risk of dyslipidemia and atherosclerosis. Thus for primordial and primary prevention of atherosclerosis, we suggest screening these children for low plasma apoA1 and high plasma apoB levels.

The Navier-Stokes equations on a bounded domain

International Nuclear Information System (INIS)

Scheffer, V.

1980-01-01

Suppose U is an open bounded subset of 3-space such that the boundary of U has Lebesgue measure zero. Then for any initial condition with finite kinetic energy we can find a global (i.e. for all time) weak solution u to the time dependent Navier-Stokes equations of incompressible fluid flow in U such that the curl of u is continuous outside a locally closed set whose 5/3 dimensional Hausdorff measure is finite. (orig.)

ApoA-I induces S1P release from endothelial cells through ABCA1 and SR-BI in a positive feedback manner.

Science.gov (United States)

Liu, Xing; Ren, Kun; Suo, Rong; Xiong, Sheng-Lin; Zhang, Qing-Hai; Mo, Zhong-Cheng; Tang, Zhen-Li; Jiang, Yue; Peng, Xiao-Shan; Yi, Guang-Hui

2016-12-01

Sphingosine-1-phosphate (S1P), which has emerged as a pivotal signaling mediator that participates in the regulation of multiple cellular processes, is derived from various cells, including vascular endothelial cells. S1P accumulates in lipoproteins, especially HDL, and the majority of free plasma S1P is bound to HDL. We hypothesized that HDL-associated S1P is released through mechanisms associated with the HDL maturation process. ApoA-I, a major HDL apolipoprotein, is a critical factor for nascent HDL formation and lipid trafficking via ABCA1. Moreover, apoA-I is capable of promoting bidirectional lipid movement through SR-BI. In the present study, we confirmed that apoA-I can facilitate the production and release of S1P by HUVECs. Furthermore, we demonstrated that ERK1/2 and SphK activation induced by apoA-I is involved in the release of S1P from HUVECs. Inhibitor and siRNA experiments showed that ABCA1 and SR-BI are required for S1P release and ERK1/2 phosphorylation induced by apoA-I. However, the effects triggered by apoA-I were not suppressed by inhibiting ABCA1/JAK2 or the SR-BI/Src pathway. S1P released due to apoA-I activation can stimulate the (ERK1/2)/SphK1 pathway through S1PR (S1P receptor) 1/3. These results indicated that apoA-I not only promotes S1P release through ABCA1 and SR-BI but also indirectly activates the (ERK1/2)/SphK1 pathway by releasing S1P to trigger their receptors. In conclusion, we suggest that release of S1P induced by apoA-I from endothelial cells through ABCA1 and SR-BI is a self-positive-feedback process: apoA-I-(ABCA1 and SR-BI)-(S1P release)-S1PR-ERK1/2-SphK1-(S1P production)-(more S1P release induced by apoA-I).

Hyperlipidemia and cutaneous abnormalities in transgenic mice overexpressing human apolipoprotein C1

NARCIS (Netherlands)

Jong, M. C.; Gijbels, M. J.; Dahlmans, V. E.; Gorp, P. J.; Koopman, S. J.; Ponec, M.; Hofker, M. H.; Havekes, L. M.

1998-01-01

Transgenic mice were generated with different levels of human apolipoprotein C1 (APOC1) expression in liver and skin. At 2 mo of age, serum levels of cholesterol, triglycerides (TG), and FFA were strongly elevated in APOC1 transgenic mice compared with wild-type mice. These elevated levels of serum

The algebras of bounded and essentially bounded Lebesgue measurable functions

Directory of Open Access Journals (Sweden)

Mortini Raymond

2017-04-01

Full Text Available Let X be a set in ℝn with positive Lebesgue measure. It is well known that the spectrum of the algebra L∞(X of (equivalence classes of essentially bounded, complex-valued, measurable functions on X is an extremely disconnected compact Hausdorff space.We show, by elementary methods, that the spectrum M of the algebra ℒb(X, ℂ of all bounded measurable functions on X is not extremely disconnected, though totally disconnected. Let ∆ = { δx : x ∈ X} be the set of point evaluations and let g be the Gelfand topology on M. Then (∆, g is homeomorphic to (X, Τdis,where Tdis is the discrete topology. Moreover, ∆ is a dense subset of the spectrum M of ℒb(X, ℂ. Finally, the hull h(I, (which is homeomorphic to M(L∞(X, of the ideal of all functions in ℒb(X, ℂ vanishing almost everywhere on X is a nowhere dense and extremely disconnected subset of the Corona M \\ ∆ of ℒb(X, ℂ.

Thyroid hormones upregulate apolipoprotein E gene expression in astrocytes

Energy Technology Data Exchange (ETDEWEB)

Roman, Corina; Fuior, Elena V.; Trusca, Violeta G. [Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest (Romania); Kardassis, Dimitris [University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Heraklion, Crete (Greece); Simionescu, Maya [Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest (Romania); Gafencu, Anca V., E-mail: anca.gafencu@icbp.ro [Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest (Romania)

2015-12-04

Apolipoprotein E (apoE), a protein mainly involved in lipid metabolism, is associated with several neurodegenerative disorders including Alzheimer's disease. Despite numerous attempts to elucidate apoE gene regulation in the brain, the exact mechanism is still uncovered. The mechanism of apoE gene regulation in the brain involves the proximal promoter and multienhancers ME.1 and ME.2, which evolved by gene duplication. Herein we questioned whether thyroid hormones and their nuclear receptors have a role in apoE gene regulation in astrocytes. Our data showed that thyroid hormones increase apoE gene expression in HTB14 astrocytes in a dose-dependent manner. This effect can be intermediated by the thyroid receptor β (TRβ) which is expressed in these cells. In the presence of triiodothyronine (T3) and 9-cis retinoic acid, in astrocytes transfected to overexpress TRβ and retinoid X receptor α (RXRα), apoE promoter was indirectly activated through the interaction with ME.2. To determine the location of TRβ/RXRα binding site on ME.2, we performed DNA pull down assays and found that TRβ/RXRα complex bound to the region 341–488 of ME.2. This result was confirmed by transient transfection experiments in which a series of 5′- and 3′-deletion mutants of ME.2 were used. These data support the existence of a biologically active TRβ binding site starting at 409 in ME.2. In conclusion, our data revealed that ligand-activated TRβ/RXRα heterodimers bind with high efficiency on tissue-specific distal regulatory element ME.2 and thus modulate apoE gene expression in the brain. - Highlights: • T3 induce a dose-dependent increase of apoE expression in astrocytes. • Thyroid hormones activate apoE promoter in a cell specific manner. • Ligand activated TRβ/RXRα bind on the distal regulatory element ME.2 to modulate apoE. • The binding site of TRβ/RXRα heterodimer is located at 409 bp on ME.2.

Thyroid hormones upregulate apolipoprotein E gene expression in astrocytes

International Nuclear Information System (INIS)

Roman, Corina; Fuior, Elena V.; Trusca, Violeta G.; Kardassis, Dimitris; Simionescu, Maya; Gafencu, Anca V.

2015-01-01

Apolipoprotein E (apoE), a protein mainly involved in lipid metabolism, is associated with several neurodegenerative disorders including Alzheimer's disease. Despite numerous attempts to elucidate apoE gene regulation in the brain, the exact mechanism is still uncovered. The mechanism of apoE gene regulation in the brain involves the proximal promoter and multienhancers ME.1 and ME.2, which evolved by gene duplication. Herein we questioned whether thyroid hormones and their nuclear receptors have a role in apoE gene regulation in astrocytes. Our data showed that thyroid hormones increase apoE gene expression in HTB14 astrocytes in a dose-dependent manner. This effect can be intermediated by the thyroid receptor β (TRβ) which is expressed in these cells. In the presence of triiodothyronine (T3) and 9-cis retinoic acid, in astrocytes transfected to overexpress TRβ and retinoid X receptor α (RXRα), apoE promoter was indirectly activated through the interaction with ME.2. To determine the location of TRβ/RXRα binding site on ME.2, we performed DNA pull down assays and found that TRβ/RXRα complex bound to the region 341–488 of ME.2. This result was confirmed by transient transfection experiments in which a series of 5′- and 3′-deletion mutants of ME.2 were used. These data support the existence of a biologically active TRβ binding site starting at 409 in ME.2. In conclusion, our data revealed that ligand-activated TRβ/RXRα heterodimers bind with high efficiency on tissue-specific distal regulatory element ME.2 and thus modulate apoE gene expression in the brain. - Highlights: • T3 induce a dose-dependent increase of apoE expression in astrocytes. • Thyroid hormones activate apoE promoter in a cell specific manner. • Ligand activated TRβ/RXRα bind on the distal regulatory element ME.2 to modulate apoE. • The binding site of TRβ/RXRα heterodimer is located at 409 bp on ME.2.

Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI as biomarkers of recovery.

Directory of Open Access Journals (Sweden)

Valentina Peta

Full Text Available There is a clear need for better biomarkers of drug-induced-liver-injury (DILI.We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI.We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled. The primary objective was to analyze the performance (AUROC of ActiTest components as predictors of recovery outcome defined as an ALT <2x the upper limit of normal (ULN, and BILI <2x ULN.After adjudication, 154 patients were considered to have DILI and 22 were considered to have acute liver injury without DILI. A multivariate regression analysis (ActiTest-DILI patent pending combining the ActiTest components without BILI and ALT (used as references, apolipoprotein-A1, haptoglobin, alpha-2-macroglobulin and GGT, age and gender, resulted in a significant prediction of recovery with 67.0% accuracy (77/115 and an AUROC of 0.724 (P<0.001 vs. no prediction 0.500. Repeated apolipoprotein-A1 and haptoglobin remained significantly higher in the DILI cases that recovered (n = 65 versus those that did not (n = 16, at inclusion, at 4-8 weeks and at 8-12 weeks. The same results were observed after stratification on APAP cases and non-APAP cases.We identified that apolipoprotein-A1 and haptoglobin had significant predictive values for the prediction of recovery at 12 weeks in DILI, enabling the construction of a new prognostic panel, the DILI-ActiTest, which needs to be independently validated.

Bioinformatic Analysis of Plasma Apolipoproteins A-I and A-II Revealed Unique Features of A-I/A-II HDL Particles in Human Plasma

Science.gov (United States)

Kido, Toshimi; Kurata, Hideaki; Kondo, Kazuo; Itakura, Hiroshige; Okazaki, Mitsuyo; Urata, Takeyoshi; Yokoyama, Shinji

2016-01-01

Plasma concentration of apoA-I, apoA-II and apoA-II-unassociated apoA-I was analyzed in 314 Japanese subjects (177 males and 137 females), including one (male) homozygote and 37 (20 males and 17 females) heterozygotes of genetic CETP deficiency. ApoA-I unassociated with apoA-II markedly and linearly increased with HDL-cholesterol, while apoA-II increased only very slightly and the ratio of apoA-II-associated apoA-I to apoA-II stayed constant at 2 in molar ratio throughout the increase of HDL-cholesterol, among the wild type and heterozygous CETP deficiency. Thus, overall HDL concentration almost exclusively depends on HDL with apoA-I without apoA-II (LpAI) while concentration of HDL containing apoA-I and apoA-II (LpAI:AII) is constant having a fixed molar ratio of 2 : 1 regardless of total HDL and apoA-I concentration. Distribution of apoA-I between LpAI and LpAI:AII is consistent with a model of statistical partitioning regardless of sex and CETP genotype. The analysis also indicated that LpA-I accommodates on average 4 apoA-I molecules and has a clearance rate indistinguishable from LpAI:AII. Independent evidence indicated LpAI:A-II has a diameter 20% smaller than LpAI, consistent with a model having two apoA-I and one apoA-II. The functional contribution of these particles is to be investigated. PMID:27526664

Apolipoprotein B-associated cholesterol is a determinant of treatment outcome in patients with chronic hepatitis C virus infection receiving anti-viral agents interferon-alpha and ribavirin.

Science.gov (United States)

Sheridan, D A; Price, D A; Schmid, M L; Toms, G L; Donaldson, P; Neely, D; Bassendine, M F

2009-06-15

Hepatitis C virus (HCV) co-opts very-low-density lipoprotein (VLDL) pathways for replication, secretion and entry into hepatocytes and associates with apolipoprotein B (apoB) in plasma. Each VLDL contains apoB-100 and variable amounts of apolipoproteins E and C, cholesterol and triglycerides. To determine whether baseline lipid levels predicted treatment outcome. Retrospective analysis was performed of 250 chronic hepatitis C (CHC) patients who had received anti-viral agents interferon-alpha and ribavirin; 165 had a sustained virological response (SVR). Pre- and post-treatment nonfasting lipid profiles were measured and non-high-density lipoprotein (non-HDL) cholesterol (i.e. apoB-associated) was calculated. Binary logistic regression analysis assessed factors independently associated with treatment outcome. There was an independent association between higher apoB-associated cholesterol (non-HDL-C) and increased odds of SVR (odds ratio 2.09, P = 0.042). In multivariate analysis, non-HDL-C was significantly lower in HCV genotype 3 (g3) than genotype 1 (P = 0.007); this was reversible upon eradication of HCVg3 (pre-treatment non-HDL-C = 2.8 mmol/L, SVR = 3.6 mmol/L, P < 0.001). Higher apoB-associated cholesterol is positively associated with treatment outcome in CHC patients receiving anti-viral therapy, possibly due to competition between apoB-containing lipoproteins and infectious low-density HCV lipo-viral particles for hepatocyte entry via shared lipoprotein receptors.

Bounds for the probability distribution function of the linear ACD process

OpenAIRE

Fernandes, Marcelo

2003-01-01

Rio de Janeiro This paper derives both lower and upper bounds for the probability distribution function of stationary ACD(p, q) processes. For the purpose of illustration, I specialize the results to the main parent distributions in duration analysis. Simulations show that the lower bound is much tighter than the upper bound.

The -1131T>C polymorphism in the apolipoprotein A5 gene is related to hypertriglyceridemia in Taiwanese aborigines.

Science.gov (United States)

Huang, Meng-Chuan; Wang, Tsu-Nai; Wang, Huan-Sen; Sung, Yi-Ching; Ko, Ying-Chin; Chiang, Hung-Che

2008-04-01

The prevalence of hypertriglyceridemia, considered to be an independent risk factor for the development of cardiovascular disease, is high in Taiwanese aborigines. This study was undertaken to examine the effect of the -1131T>C polymorphism in the apolipoprotein A5 gene on serum triglyceride levels in female Taiwanese aborigines. This was a cross-sectional study, and a total of 316 unrelated female Taiwanese aborigines were genotyped at the -1131T>C polymorphism in apolipoprotein A5 using the polymerase chain reaction-restriction fragment length polymorphism method. Serum triglyceride > or = 150 mg/dL was defined as the hypertriglyceridemia group and triglyceride Japanese and Han Chinese, but was higher than that in Caucasians. In a multiple logistic model adjusted for possible confounders, C allele-containing variants were independently associated with greater risks (CT genotype: OR = 3.28, 95% CI = 1.43-7.56; CC genotype: OR = 5.86, 95% CI = 2.15-15.99) of hypertriglyceridemia than the TT genotype (p fashion (for trend, p C polymorphism of the Apo A5 gene influences serum triglyceride levels in female Taiwanese aborigines, and that differences exist in the frequency of the C allele among people of various ethnicities.

A systematic review and meta-analysis of randomized controlled trials of the effect of konjac glucomannan, a viscous soluble fiber, on LDL cholesterol and the new lipid targets non-HDL cholesterol and apolipoprotein B.

Science.gov (United States)

Ho, Hoang Vi Thanh; Jovanovski, Elena; Zurbau, Andreea; Blanco Mejia, Sonia; Sievenpiper, John L; Au-Yeung, Fei; Jenkins, Alexandra L; Duvnjak, Lea; Leiter, Lawrence; Vuksan, Vladimir

2017-05-01

Background: Evidence from randomized controlled trials (RCTs) suggests the consumption of konjac glucomannan (KJM), a viscous soluble fiber, for improving LDL-cholesterol concentrations. It has also been suggested that the cholesterol-lowering potential of KJM may be greater than that of other fibers. However, trials have been relatively scarce and limited in sample size and duration, and the effect estimates have been inconsistent. The effect of KJM on new lipid targets of cardiovascular disease (CVD) risk is also unknown. Objective: This systematic review and meta-analysis aimed to assess the effect of KJM on LDL cholesterol, non-HDL cholesterol, and apolipoprotein B. Design: Medline, Embase, CINAHL, and the Cochrane Central databases were searched. We included RCTs with a follow-up of ≥3 wk that assessed the effect of KJM on LDL cholesterol, non-HDL cholesterol, or apolipoprotein B. Data were pooled by using the generic inverse-variance method with random-effects models and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I 2 statistic. Results: Twelve studies ( n = 370), 8 in adults and 4 in children, met the inclusion criteria. KJM significantly lowered LDL cholesterol (MD: -0.35 mmol/L; 95% CI: -0.46, -0.25 mmol/L) and non-HDL cholesterol (MD: -0.32 mmol/L; 95% CI: -0.46, -0.19 mmol/L). Data from 6 trials suggested no impact of KJM on apolipoprotein B. Conclusions: Our findings support the intake of ∼3 g KJM/d for reductions in LDL cholesterol and non-HDL cholesterol of 10% and 7%, respectively. The information may be of interest to health agencies in crafting future dietary recommendations related to reduction in CVD risk. This study was registered at clinicaltrials.gov as NCT02068248. © 2017 American Society for Nutrition.

Quantitation of apolipoprotein epsilon gene expression by competitive polymerase chain reaction in a patient with familial apolipoprotein E deficiency.

Science.gov (United States)

Dobmeyer, J M; Rexin, M; Dobmeyer, T S; Klein, S A; Rossol, R; Feussner, G

1998-06-22

A simple method of obtaining semiquantitative and reliable data on apolipoprotein (apo) sigma gene expression is described. We detected apo sigma specific sequences by reverse transcription (rT)-PCR. For quantitative measurement, an apo sigma DNA standard was produced allowing the development of a competitive PCR-method. The efficiency of RNA extraction and cDNA synthesis was controlled by quantitation of a housekeeping gene (glyceraldehyde-3-phosphatedehydrogenase, G3PDH) in separate reactions. To imitate a defined induction of apo sigma gene expression, serial twofold dilutions of total RNA were reversely transcribed and the respective cDNAs used to perform a competitive apo sigma and G3PDH PCR. The change in apo sigma cDNA and G3PDH cDNA was 1.7-2.3-fold with an expected value of 2.0-fold. Standard deviations in three independently performed experiments were within a range of < 15% of the mean, indicating low intra-assay variation and high reproducibility. To illustrate this method, apo sigma gene expression was measured in a patient with complete lack of functional active apo E in comparison to healthy controls. The method presented here might be valuable in assessment of apo sigma gene expression in human disease.

Perceptron Mistake Bounds

OpenAIRE

Mohri, Mehryar; Rostamizadeh, Afshin

2013-01-01

We present a brief survey of existing mistake bounds and introduce novel bounds for the Perceptron or the kernel Perceptron algorithm. Our novel bounds generalize beyond standard margin-loss type bounds, allow for any convex and Lipschitz loss function, and admit a very simple proof.

Characteristics of the formation of enzyme-bound ATP from medium inorganic phosphate by mitochondrial F1 adenosinetriphosphatase in the presence of dimethyl sulfoxide

International Nuclear Information System (INIS)

Kandpal, R.P.; Stempel, K.E.; Boyer, P.D.

1987-01-01

Addition of dimethyl sulfoxide promotes the formation of enzyme-bound ATP from medium P/sub i/ by mitochondrial F 1 adenosinetriphosphatase that has tightly bound ADP present. Measurements are reported of medium P/sub i/ ↔ H 18 OH exchange and of the dependence of formation of enzyme-bound ATP on P/sub i/ concentration. Attainment of an apparent equilibrium between medium P/sub i/ and bound ATP requires longer than 30 min, even though the rates of P/sub i/ binding and release after apparent equilibrium is reached would suffice for a faster approach to equilibrium. Slow protein conformational changes or other unknown modulating factors may be responsible for the slow rate of bound ATP formation. After apparent equilibrium is reached, each P/sub i/ that binds to the enzyme reversibly forms ATP about 50 times before being released to the medium. The rate of interconversion of bound ATP to bound ADP and P/sub i/ is much slower than that in the absence of dimethyl sulfoxide as measured with sufficient low ATP concentrations so that single-site catalysis is favored. Although the interconversion rate is slowed, the equilibrium constant for bound ATP formation from bound ADP and P/sub i/ is not far from unity. Dimethyl sulfoxide favors the formation of enzyme-bound ATP by promoting the competent binding of P/sub i/ to enzyme with ADP bound at a catalytic site rather than by promoting formation of bound ATP from bound ADP and P/sub i/

A narrow quasi-bound state of the DNN system

International Nuclear Information System (INIS)

Doté, A.; Bayar, M.; Xiao, C.W.; Hyodo, T.; Oka, M.; Oset, E.

2013-01-01

We have investigated a charmed system of DNN (composed of two nucleons and a D meson) by a complementary study with a variational calculation and a Faddeev calculation with fixed-center approximation (Faddeev-FCA). In the present study, we employ a DN potential based on a vector–meson exchange picture in which a resonant Λ c (2595) is dynamically generated as a DN quasi-bound state, similarly to the Λ(1405) as a K ¯ N one in the strange sector. As a result of the study of variational calculation with an effective DN potential and three kinds of NN potentials, the DNN(J π =0 − ,I=1/2) is found to be a narrow quasi-bound state below Λ c (2595)N threshold: total binding energy ∼225 MeV and mesonic decay width ∼25 MeV. On the other hand, the J π =1 − state is considered to be a scattering state of Λ c (2595) and a nucleon. These results are essentially supported by the Faddeev-FCA calculation. By the analysis of the variational wave function, we have found a unique structure in the DNN(J π =0 − ,I=1/2) such that the D meson stays around the center of the total system due to the heaviness of the D meson

Apolipoprotein D Internalization Is a Basigin-dependent Mechanism.

Science.gov (United States)

Najyb, Ouafa; Brissette, Louise; Rassart, Eric

2015-06-26

Apolipoprotein D (apoD), a member of the lipocalin family, is a 29-kDa secreted glycoprotein that binds and transports small lipophilic molecules. Expressed in several tissues, apoD is up-regulated under different stress stimuli and in a variety of pathologies. Numerous studies have revealed that overexpression of apoD led to neuroprotection in various mouse models of acute stress and neurodegeneration. This multifunctional protein is internalized in several cells types, but the specific internalization mechanism remains unknown. In this study, we demonstrate that the internalization of apoD involves a specific cell surface receptor in 293T cells, identified as the transmembrane glycoprotein basigin (BSG, CD147); more particularly, its low glycosylated form. Our results show that internalized apoD colocalizes with BSG into vesicular compartments. Down-regulation of BSG disrupted the internalization of apoD in cells. In contrast, overexpression of basigin in SH-5YSY cells, which poorly express BSG, restored the uptake of apoD. Cyclophilin A, a known ligand of BSG, competitively reduced apoD internalization, confirming that BSG is a key player in the apoD internalization process. In summary, our results demonstrate that basigin is very likely the apoD receptor and provide additional clues on the mechanisms involved in apoD-mediated functions, including neuroprotection. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Generalized Hofmann quantum process fidelity bounds for quantum filters

Science.gov (United States)

Sedlák, Michal; Fiurášek, Jaromír

2016-04-01

We propose and investigate bounds on the quantum process fidelity of quantum filters, i.e., probabilistic quantum operations represented by a single Kraus operator K . These bounds generalize the Hofmann bounds on the quantum process fidelity of unitary operations [H. F. Hofmann, Phys. Rev. Lett. 94, 160504 (2005), 10.1103/PhysRevLett.94.160504] and are based on probing the quantum filter with pure states forming two mutually unbiased bases. Determination of these bounds therefore requires far fewer measurements than full quantum process tomography. We find that it is particularly suitable to construct one of the probe bases from the right eigenstates of K , because in this case the bounds are tight in the sense that if the actual filter coincides with the ideal one, then both the lower and the upper bounds are equal to 1. We theoretically investigate the application of these bounds to a two-qubit optical quantum filter formed by the interference of two photons on a partially polarizing beam splitter. For an experimentally convenient choice of factorized input states and measurements we study the tightness of the bounds. We show that more stringent bounds can be obtained by more sophisticated processing of the data using convex optimization and we compare our methods for different choices of the input probe states.

The effect of an apolipoprotein A-I-containing high-density lipoprotein-mimetic particle (CER-001) on carotid artery wall thickness in patients with homozygous familial hypercholesterolemia: The Modifying Orphan Disease Evaluation (MODE) study.

Science.gov (United States)

Hovingh, G Kees; Smits, Loek P; Stefanutti, Claudia; Soran, Handrean; Kwok, See; de Graaf, Jacqueline; Gaudet, Daniel; Keyserling, Constance H; Klepp, Heather; Frick, Jennifer; Paolini, John F; Dasseux, Jean-Louis; Kastelein, John J P; Stroes, Erik S

2015-05-01

Patients with homozygous familial hypercholesterolemia (HoFH) are at extremely elevated risk for early cardiovascular disease because of exposure to elevated low-density lipoprotein cholesterol (LDL-C) plasma levels from birth. Lowering LDL-C by statin therapy is the cornerstone for cardiovascular disease prevention, but the residual risk in HoFH remains high, emphasizing the need for additional therapies. In the present study, we evaluated the effect of serial infusions with CER-001, a recombinant human apolipoprotein A-I (apoA-I)-containing high-density lipoprotein-mimetic particle, on carotid artery wall dimensions in patients with HoFH. Twenty-three patients (mean age 39.4 ± 13.5 years, mean LDL-C 214.2 ± 81.5 mg/dL) with genetically confirmed homozygosity or compound heterozygosity for LDLR, APOB, PCSK9, or LDLRAP1 mutations received 12 biweekly infusions with CER-001 (8 mg/kg). Before and 1 hour after the first infusion, lipid values were measured. Magnetic resonance imaging (3-T magnetic resonance imaging) scans of the carotid arteries were acquired at baseline and after 24 weeks to assess changes in artery wall dimensions. After CER-001 infusion, apoA-I increased from 114.8 ± 20.7 mg/dL to 129.3 ± 23.0 mg/dL. After 24 weeks, mean vessel wall area (primary end point) decreased from 17.23 to 16.75 mm(2) (P = .008). A trend toward reduction of mean vessel wall thickness was observed (0.75 mm at baseline and 0.74 mm at follow-up, P = .0835). In HoFH, 12 biweekly infusions with an apoA-I-containing high-density lipoprotein-mimetic particle resulted in a significant reduction in carotid mean vessel wall area, implying that CER-001 may reverse atherogenic changes in the arterial wall on top of maximal low-density lipoprotein-lowering therapy. This finding supports further clinical evaluation of apoA-I-containing particles in patients with HoFH. Copyright © 2015 Mosby, Inc. All rights reserved.

Evolution of protein bound Maillard reaction end-products and free Amadori compounds in low lactose milk in presence of fructosamine oxidase I.

Science.gov (United States)

Troise, Antonio Dario; Buonanno, Martina; Fiore, Alberto; Monti, Simona Maria; Fogliano, Vincenzo

2016-12-01

Thermal treatments and storage influence milk quality, particularly in low lactose milk as the higher concentration of reducing sugars can lead to the increased formation of the Maillard reaction products (MRPs). The control of the Amadori products (APs) formation is the key step to mitigate the Maillard reaction (MR) in milk. The use of fructosamine oxidases, (Faox) provided promising results. In this paper, the effects of Faox I were evaluated by monitoring the concentration of free and bound MRPs in low lactose milk during shelf life. Results showed that the enzyme reduced the formation of protein-bound MRPs down to 79% after six days at 37°C. Faox I lowered the glycation of almost all the free amino acids resulting effective on basic and polar amino acids. Data here reported corroborate previous findings on the potentiality of Faox enzymes in controlling the early stage of the MR in foods. Copyright © 2016 Elsevier Ltd. All rights reserved.

Class-specific Error Bounds for Ensemble Classifiers

Energy Technology Data Exchange (ETDEWEB)

Prenger, R; Lemmond, T; Varshney, K; Chen, B; Hanley, W

2009-10-06

The generalization error, or probability of misclassification, of ensemble classifiers has been shown to be bounded above by a function of the mean correlation between the constituent (i.e., base) classifiers and their average strength. This bound suggests that increasing the strength and/or decreasing the correlation of an ensemble's base classifiers may yield improved performance under the assumption of equal error costs. However, this and other existing bounds do not directly address application spaces in which error costs are inherently unequal. For applications involving binary classification, Receiver Operating Characteristic (ROC) curves, performance curves that explicitly trade off false alarms and missed detections, are often utilized to support decision making. To address performance optimization in this context, we have developed a lower bound for the entire ROC curve that can be expressed in terms of the class-specific strength and correlation of the base classifiers. We present empirical analyses demonstrating the efficacy of these bounds in predicting relative classifier performance. In addition, we specify performance regions of the ROC curve that are naturally delineated by the class-specific strengths of the base classifiers and show that each of these regions can be associated with a unique set of guidelines for performance optimization of binary classifiers within unequal error cost regimes.

Lower bounds on scintillation detector timing performance

International Nuclear Information System (INIS)

Clinthorne, N.H.; Rogers, W.L.; Hero, A.O. III.; Petrick, N.A.

1990-01-01

Fundamental method-independent limits on the timing performance of scintillation detectors are useful for identifying regimes in which either present timing methods are nearly optimal or where a considerable performance gain might be realized using better pulse processing techniques. Several types of lower bounds on mean-squared timing error (MSE) performance have been developed and applied to scintillation detectors. The simple Cramer-Rao (CR) bound can be useful in determining the limiting MSE for scintillators having a relatively high rate of photon problction such as BaF 2 and NaI(Tl); however, it tends to overestimate the achievalbe performance for scintillators with lower rates such as BGO. For this reason, alternative bounds have been developed using rate-distortion theory or by assuming that the conversion of energy to scintillation light must pass through excited states which have exponential lifetime densities. The bounds are functions of the mean scintillation pulse shape, the scintillation intensity, and photodetector characteristics; they are simple to evaluate and can be used to conveniently assess the limiting timing performance of scintillation detectors. (orig.)

Existence of B/E and E receptors on Hep-G2 cells: a study using colloidal gold- and 125I-labeled lipoproteins

International Nuclear Information System (INIS)

Hesz, A.; Ingolic, E.; Krempler, F.; Kostner, G.M.

1987-01-01

The presence of specific receptors for apolipoprotein B (low-density lipoproteins) and apolipoprotein E (HDL-E) on Hep-G2 cells and human skin fibroblasts was studied by chemical methods and by electron microscopy using a differential gold labeling technique. Fibroblasts bound both types of lipoproteins to one and the same receptor (B/E receptor) as deduced from competition experiments with HDL-E and LDL. Labeled HDL-E, on the other hand, was only partially displaced by cold LDL but was completely displaced by unlabeled HDL-E. Scatchard analysis of lipoprotein binding to Hep-G2 cells revealed an approx 10 times higher binding affinity of apoE-containing lipoproteins as compared to apoB-containing ones. No differences between apoE- or apoB-containing lipoproteins with respect to the morphology of cell binding and intracellular processing were observed. The results are compatible with the concept that Hep-G2 cells possess two kinds of receptors, one specific for apoB- and apoE-containing lipoproteins (B/E receptor) and another specific for apoE only. From these studies we conclude that Hep-G2 cells may serve as a suitable model for studying the lipoprotein metabolism in the liver

Selection on alleles affecting human longevity and late-life disease: the example of apolipoprotein E.

Directory of Open Access Journals (Sweden)

Fotios Drenos

2010-04-01

Full Text Available It is often claimed that genes affecting health in old age, such as cardiovascular and Alzheimer diseases, are beyond the reach of natural selection. We show in a simulation study based on known genetic (apolipoprotein E and non-genetic risk factors (gender, diet, smoking, alcohol, exercise that, because there is a statistical distribution of ages at which these genes exert their influence on morbidity and mortality, the effects of selection are in fact non-negligible. A gradual increase with each generation of the epsilon2 and epsilon3 alleles of the gene at the expense of the epsilon4 allele was predicted from the model. The epsilon2 allele frequency was found to increase slightly more rapidly than that for epsilon3, although there was no statistically significant difference between the two. Our result may explain the recent evolutionary history of the epsilon 2, 3 and 4 alleles of the apolipoprotein E gene and has wider relevance for genes affecting human longevity.

Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen

International Nuclear Information System (INIS)

Eaton, D.L.; Fless, G.M.; Kohr, W.J.; McLean, J.W.; Xu, Q.T.; Miller, C.G.; Lawn, R.M.; Scanu, A.M.

1987-01-01

Apolipoprotein(a) [apo(a)] is a glycoprotein with M/sub r/ ∼ 280,000 that is disulfide linked to apolipoprotein B in lipoprotein(a) particles. Elevated plasma levels of lipoprotein(a) are correlated with atherosclerosis. Partial amino acid sequence of apo(a) shows that it has striking homology to plasminogen. Plasminogen is a plasma serine protease zymogen that consists of five homologous and tandemly repeated domains called kringles and a trypsin-like protease domain. The amino-terminal sequence obtained for apo(a) is homologous to the beginning of kringle 4 but not the amino terminus of plasminogen. Apo(a) was subjected to limited proteolysis by trypsin or V8 protease, and fragments generated were isolated and sequenced. Sequences obtained from several of these fragments are highly (77-100%) homologous to plasminogen residues 391-421, which reside within kringle 4. Analysis of these internal apo(a) sequences revealed that apo(a) may contain at least two kringle 4-like domains. A sequence obtained from another tryptic fragment also shows homology to the end of kringle 4 and the beginning of kringle 5. Sequence data obtained from the two tryptic fragments shows homology with the protease domain of plasminogen. One of these sequences is homologous to the sequences surrounding the activation site of plasminogen. Plasminogen is activated by the cleavage of a specific arginine residue by urokinase and tissue plasminogen activator; however, the corresponding site in apo(a) is a serine that would not be cleaved by tissue plasminogen activator or urokinase. Using a plasmin-specific assay, no proteolytic activity could be demonstrated for lipoprotein(a) particles. These results suggest that apo(a) contains kringle-like domains and an inactive protease domain

A strongly quasiconvex PAC-Bayesian bound

DEFF Research Database (Denmark)

Thiemann, Niklas; Igel, Christian; Wintenberger, Olivier

2017-01-01

We propose a new PAC-Bayesian bound and a way of constructing a hypothesis space, so that the bound is convex in the posterior distribution and also convex in a trade-off parameter between empirical performance of the posterior distribution and its complexity. The complexity is measured by the Ku...

Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristics

DEFF Research Database (Denmark)

Rune, Ida; Rolin, Bidda; Lykkesfeldt, Jens

2018-01-01

In the apolipoprotein E-deficient mouse, the gut microbiota has an impact on the development of atherosclerosis, but whether such correlations are also present in rats requires investigation. Therefore, we studied female SD-Apoe tm1sage (Apoe -/-) rats fed either a Western diet or a low-fat control...

Apolipoprotein C3 deficiency results in diet-induced obesity and aggravated insulin resistance in mice

NARCIS (Netherlands)

Duivenvoorden, Ilse; Teusink, Bas; Rensen, Patrick C.; Romijn, Johannes A.; Havekes, Louis M.; Voshol, Peter J.

2005-01-01

Our aim was to study whether the absence of apolipoprotein (apo) C3, a strong inhibitor of lipoprotein lipase (LPL), accelerates the development of obesity and consequently insulin resistance. Apoc3(-/-) mice and wild-type littermates were fed a high-fat (46 energy %) diet for 20 weeks. After 20

Circuit lower bounds in bounded arithmetics

Czech Academy of Sciences Publication Activity Database

Pich, Ján

2015-01-01

Roč. 166, č. 1 (2015), s. 29-45 ISSN 0168-0072 R&D Projects: GA AV ČR IAA100190902 Keywords : bounded arithmetic * circuit lower bounds Subject RIV: BA - General Mathematics Impact factor: 0.582, year: 2015 http://www.sciencedirect.com/science/article/pii/S0168007214000888

Spectroscopic constants and the potential energy curve of the iodine weakly bound 0+g state correlating with the I(2P1/2) + I(2P1/2) dissociation limit

International Nuclear Information System (INIS)

Akopyan, M E; Baturo, V V; Lukashov, S S; Poretsky, S A; Pravilov, A M

2013-01-01

The stepwise three-step three-colour aser excitation scheme and rotational as well as rovibrational energy transfer processes in the 0 + g state induced by collisions with He and Ar atoms are used for determination of rovibronic level energies of the weakly bound 0 + g state correlating with the I( 2 P 1/2 ) + I( 2 P 1/2 ) dissociation limit. Dunham coefficients of the state, Y i0 (i = 0–3), Y i1 (i = 0–3) and Y 02 for the v 0 g + = 0–16 and J 0 g + ≈ 14–135 ranges as well as the dissociation energy of the state, D e , and equilibrium I–I distance of the state, R e , are determined. The potential energy curve of the state constructed using these constants is also reported. (paper)

Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer's disease.

OpenAIRE

Harrington, C. R.; Louwagie, J.; Rossau, R.; Vanmechelen, E.; Perry, R. H.; Perry, E. K.; Xuereb, J. H.; Roth, M.; Wischik, C. M.

1994-01-01

Alzheimer's disease (AD) is associated with an increased frequency of the apolipoprotein E type epsilon 4 allele. To address both the disease and the allele specificity of this association, we have examined the apolipoprotein E allele distribution in 255 elderly persons including those with autopsy-confirmed AD, senile dementia of the Lewy body type (SDLT), vascular dementia, Parkinson's disease (PD) or Huntington's disease and in nondemented controls either with or without coronary complicat...

Apolipoprotein E gene polymorphism and Alzheimer's disease in Chinese population: a meta-analysis

Science.gov (United States)

Liu, Mengying; Bian, Chen; Zhang, Jiqiang; Wen, Feng

2014-03-01

The relationship between Apolipoprotein E (ApoE) genotype and the risk of Alzheimer's disease (AD) is relatively well established in Caucasians, but less established in other ethnicities. To examine the association between ApoE polymorphism and the onset of AD in Chinese population, we searched the commonly used electronic databases between January 2000 and November 2013 for relevant studies. Total 20 studies, including 1576 cases and 1741 controls, were retrieved. The results showed statistically significant positive association between risk factor ɛ4 allele carriers and AD in Chinese population (OR = 3.93, 95% CI = 3.37-4.58, P risk suffering from AD than controls in Chinese population. The results also provide a support for the protection effect of ApoE ɛ3 allele in developing AD.

Apolipoprotein(a) in insulin-dependent diabetic patients with and without diabetic nephropathy

DEFF Research Database (Denmark)

Gall, M A; Rossing, P; Hommel, E

1992-01-01

Insulin-dependent diabetic patients with diabetic nephropathy have a highly increased morbidity and mortality from cardiovascular diseases. To determine whether altered levels of apolipoprotein(a) (apo(a)), the glycoprotein of the potentially atherogenic lipoprotein(a) (Lp(a)), contribute...... to the increased risk of ischaemic heart disease, apo(a) was determined in 50 insulin-dependent diabetic patients with diabetic nephropathy (group 1), in 50 insulin-dependent diabetic patients with microalbuminuria (group 2), in 50 insulin-dependent diabetic patients with normoalbuminuria (group 3), and in 50...... healthy subjects (group 4). The groups were matched with regard to sex, age and body mass index. The diabetic groups were also matched with regard to diabetes duration. The level of apo(a) was approximately the same in the four groups, being: 122 (x/ divided by 4.2) U l-1, 63 (x/ divided by 4.4) U l-1...

Rovibrational bound states of SO2 isotopologues. I: Total angular momentum J = 0-10

Science.gov (United States)

Kumar, Praveen; Ellis, Joseph; Poirier, Bill

2015-04-01

Isotopic variation of the rovibrational bound states of SO2 for the four stable sulfur isotopes 32-34,36S is investigated in comprehensive detail. In a two-part series, we compute the low-lying energy levels for all values of total angular momentum in the range J = 0-20. All rovibrational levels are computed, to an extremely high level of numerical convergence. The calculations have been carried out using the ScalIT suite of parallel codes. The present study (Paper I) examines the J = 0-10 rovibrational levels, providing unambiguous symmetry and rovibrational label assignments for each computed state. The calculated vibrational energy levels exhibit very good agreement with previously reported experimental and theoretical data. Rovibrational energy levels, calculated without any Coriolis approximations, are reported here for the first time. Among other potential ramifications, this data will facilitate understanding of the origin of mass-independent fractionation of sulfur isotopes in the Archean rock record-of great relevance for understanding the "oxygen revolution".

Phosphatidylinositol 3-Kinase (PI3K) Activity Bound to Insulin-like Growth Factor-I (IGF-I) Receptor, which Is Continuously Sustained by IGF-I Stimulation, Is Required for IGF-I-induced Cell Proliferation*

Science.gov (United States)

Fukushima, Toshiaki; Nakamura, Yusaku; Yamanaka, Daisuke; Shibano, Takashi; Chida, Kazuhiro; Minami, Shiro; Asano, Tomoichiro; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

2012-01-01

Continuous stimulation of cells with insulin-like growth factors (IGFs) in G1 phase is a well established requirement for IGF-induced cell proliferation; however, the molecular components of this prolonged signaling pathway that is essential for cell cycle progression from G1 to S phase are unclear. IGF-I activates IGF-I receptor (IGF-IR) tyrosine kinase, followed by phosphorylation of substrates such as insulin receptor substrates (IRS) leading to binding of signaling molecules containing SH2 domains, including phosphatidylinositol 3-kinase (PI3K) to IRS and activation of the downstream signaling pathways. In this study, we found prolonged (>9 h) association of PI3K with IGF-IR induced by IGF-I stimulation. PI3K activity was present in this complex in thyrocytes and fibroblasts, although tyrosine phosphorylation of IRS was not yet evident after 9 h of IGF-I stimulation. IGF-I withdrawal in mid-G1 phase impaired the association of PI3K with IGF-IR and suppressed DNA synthesis the same as when PI3K inhibitor was added. Furthermore, we demonstrated that Tyr1316-X-X-Met of IGF-IR functioned as a PI3K binding sequence when this tyrosine is phosphorylated. We then analyzed IGF signaling and proliferation of IGF-IR−/− fibroblasts expressing exogenous mutant IGF-IR in which Tyr1316 was substituted with Phe (Y1316F). In these cells, IGF-I stimulation induced tyrosine phosphorylation of IGF-IR and IRS-1/2, but mutated IGF-IR failed to bind PI3K and to induce maximal phosphorylation of GSK3β and cell proliferation in response to IGF-I. Based on these results, we concluded that PI3K activity bound to IGF-IR, which is continuously sustained by IGF-I stimulation, is required for IGF-I-induced cell proliferation. PMID:22767591

Human apolipoprotein E genotypes differentially modify house dust mite-induced airway disease in mice

DEFF Research Database (Denmark)

Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin

2012-01-01

Apolipoprotein E (apoE) is an endogenous negative regulator of airway hyperreactivity (AHR) and mucous cell metaplasia in experimental models of house dust mite (HDM)-induced airway disease. The gene encoding human apoE is polymorphic, with three common alleles (e2, e3, and e4) reflecting single ...

Severe hypertriglyceridemia in human APOC1 transgenic mice is caused by apoC-I-induced inhibition of LPL

NARCIS (Netherlands)

Berbée, J.F.P.; Hoogt, C.C. van der; Sundararaman, D.; Havekes, L.M.; Rensen, P.C.N.

2005-01-01

Studies in humans and mice have shown that increased expression of apolipoprotein C-I (apoC-I) results in combined hyperlipidemia with a more pronounced effect on triglycerides (TGs) compared with total cholesterol (TC). The aim of this study was to elucidate the main reason for this effect using

Suppressive effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient mice.

Science.gov (United States)

Natsume, Midori; Baba, Seigo

2014-01-01

Previous studies in humans have shown that the cacao polyphenols, (-)-epicatechin and its oligomers, prevent in vitro and ex vivo low-density lipoprotein oxidation mediated by free radical generators and metal ions and also reduce plasma LDL-cholesterol levels. The aim of this study was to examine the effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice. Mice aged 8 weeks (n = 90) were randomized into three groups, and fed either normal mouse chow (controls) or chow supplemented with 0.25 or 0.40 % cacao polyphenols for 16 weeks. The mean plaque area in cross-sections of the brachiocephalic trunk was measured and found to be lower in the 0.25 % cacao polyphenol group than in the control group (p cacao polyphenol group (p cacao polyphenols inhibit the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice by reducing oxidative stress and inflammatory responses.

Apolipoprotein M binds oxidized phospholipids and increases the antioxidant effect of HDL

DEFF Research Database (Denmark)

Elsøe, Sara; Ahnström, Josefin; Christoffersen, Christina

2012-01-01

Oxidation of LDL plays a key role in the development of atherosclerosis. HDL may, in part, protect against atherosclerosis by inhibiting LDL oxidation. Overexpression of HDL-associated apolipoprotein M (apoM) protects mice against atherosclerosis through a not yet clarified mechanism. Being a lip...... a lipocalin, apoM contains a binding pocket for small lipophilic molecules. Here, we report that apoM likely serves as an antioxidant in HDL by binding oxidized phospholipids, thus enhancing the antioxidant potential of HDL....

LNA-enhanced detection of single nucleotide polymorphisms in the apolipoprotein E

DEFF Research Database (Denmark)

Jacobsen, Nana; Bentzen, Joan; Meldgaard, Michael

2002-01-01

Genotyping of single nucleotide polymorphisms (SNPs) in large populations presents a great challenge, especially if the SNPs are embedded in GC-rich regions, such as the codon 112 SNP in the human apolipoprotein E (apoE). In the present study, we have used immobilized locked nucleic acid (LNA...... was applied to a panel of patient samples with simultaneous genotyping of the patients by DNA sequencing. The apoE genotyping assays for the codons 112 and 158 SNPs resulted in unambiguous results for all patient samples, concurring with those obtained by DNA sequencing....

The effect of the addition of resistance training to a dietary education intervention on apolipoproteins and diet quality in overweight and obese older adults

Directory of Open Access Journals (Sweden)

Valente EA

2011-09-01

Full Text Available Elizabeth A Valente1, Megan E Sheehy1, Joshua J Avila2, Julie A Gutierres2, Matthew J Delmonico2, Ingrid E Lofgren11Department of Nutrition and Food Sciences, 2Department of Kinesiology, University of Rhode Island, Kingston, RI, USAObjectives: The aim of the study was to examine the additive effect of resistance training (RT to a dietary education (DE intervention on emerging coronary heart disease (CHD risk factors, concentration of apolipoproteins B (apoB and A-I (apoA-I, and Dietary Approaches to Stop Hypertension (DASH Diet Index scores in overweight and obese older adults.Patients and methods: This was an ancillary study of a randomized clinical trial held in the Fall of 2008 at the University of Rhode Island. Participants were overweight or obese subjects (mean body mass index [BMI] of 31.7 kg/m2 randomized into two groups, one participating in DE only (n = 12 and the other participating in DE plus RT (DERT (n = 15. The intervention involved all subjects participating in 30 minutes of DE per week for 10 weeks. Subjects in the DERT group participated in an additional 40 minutes of RT three times per week for 10 weeks. Measurements taken were anthropometric (height, weight, waist circumference, and body composition using the BOD POD® [Body Composition System, v 2.14; Life Measurement Instruments, Concord, CA], clinical (blood pressure, and biochemical (lipid profile and apoB and apoA-I concentrations, and the DASH Diet Index was used to measure diet quality.Results: 27 subjects (11 males, 16 females, with a mean age of 66.6 ± 4.3 years, were included in analyses. The DERT subjects had significantly better triacylglycerol and apoB concentrations and DASH Diet Index scores than the DE subjects post-intervention. Improvements were seen within the DE group in energy intake, fat-free mass, and systolic blood pressure and within the DERT group in body weight, percentage of body fat, BMI, diastolic blood pressure, and oxidized low

Plasma apolipoprotein M is reduced in metabolic syndrome but does not predict intima media thickness

DEFF Research Database (Denmark)

Dullaart, Robin P F; Plomgaard, Peter; de Vries, Rindert

2009-01-01

BACKGROUND: Apolipoprotein (apo) M may exert anti-atherogenic properties in experimental studies. Its hepatic gene expression may be linked to glucose and lipid metabolism. Plasma apoM is decreased in obese mouse models. We hypothesized that plasma apoM is lower in metabolic syndrome (Met...

Apolipoprotein E and cardiovascular disease

Directory of Open Access Journals (Sweden)

Adriana Moreno Valladares

2006-01-01

Full Text Available Apolipoprotein E is a polymorphic glycoprotein who interacts with the lipoprotein receptors (LRP-Receptor Related Protein and the receptors for low density lipoproteins of (LDL receptors. When lipoproteins bring up the receptors begins lipids captation and degradation which allows cholesterol utilization, taking place an intracellular auto regulation. The three isoforms of greater importance: Apo E2, E3 and E4 are product of three alleles e2, e3, e4 of one only gene. This factor is related with the amount of lipoproteins that contains ApoE for E/B receptors. A low concentration of lipoproteins with ApoE can increase the activity of LDL receptors and consequently downward the circulating LDL. In the other hand particles with Apo E3 or Apo E4, can cause a downward regulation of LDL and in this way produces a LDL plasma elevation. Many studies in human populations have concluded that this polymorphism of apoE and the plasma variation of lipoproteins are associated with cardiovascular risk. Cardiovascular disease is the result of different interaction between factors which are genetic factor specially ApoE polymorphism e4 allelic of ApoE can explain, in some degree, the greater frequency of cardiovascular disease in those who carries it.

Computationally efficient analytic representations of relativistic bound-bound, bound-unbound and unbound-unbound transition matrix elements of hydrogenic atoms

International Nuclear Information System (INIS)

Soldatov, A.; Seke, J.; Adam, G.; Polak, M.

2008-01-01

Full text: A closed analytic form for relativistic transition matrix elements between bound-bound, bound-unbound and unbound-unbound relativistic eigenstates of hydrogenic atoms by using the plane-wave expansion for the electromagnetic-field vector potential was derived in a form convenient for large-scale numerical calculations in QED. By applying the obtained formulae, these transition matrix elements can be evaluated analytically and numerically. These exact matrix elements, which to our knowledge have not been calculated as yet, are of great importance in the analysis of various atom-field interaction processes where retardation effects cannot be ignored. The ultimate goal of the ongoing research is to develop a general universal calculation technique for Seke's approximation and renormalization method in QED, for which the usage of the plane vector expansion for the vector potential is a preferable choice. However, our primary interest lies in the Lamb-shift calculation. Our nearest objective is to carry out the plain-style relativistic calculations of the Lamb shift of the energy levels of hydrogen-like atoms and ions from first principles in the second and higher perturbative orders, using the corresponding convenient as well as novel expressions for the magnitude in question as they stand, i.e. without any additional approximations. Due to that there is no way to achieve all the above-declared goals without recourse to large-scale laborious and time-consuming high-precision numerical calculations, having the transition matrix elements of all possible types in an analytic, convenient for their efficient numerical evaluation form, would be highly advantageous and even unavoidable, especially for calculations of various QED effects in higher perturbative orders be it, equally, in traditional or novel approach. (author)

The DMM Bound

DEFF Research Database (Denmark)

Emiris, Ioannis Z.; Mourrain, Bernard; Tsigaridas, Elias

2010-01-01

) resultant by means of mixed volume, as well as recent advances on aggregate root bounds for univariate polynomials, and are applicable to arbitrary positive dimensional systems. We improve upon Canny's gap theorem [7] by a factor of O(dn-1), where d bounds the degree of the polynomials, and n is the number...... bound on the number of steps that subdivision-based algorithms perform in order to isolate all real roots of a polynomial system. This leads to the first complexity bound of Milne's algorithm [22] in 2D....

Effect of exercise and menstrual cycle status on plasma lipids, low density lipoprotein particle size, and apolipoproteins.

Science.gov (United States)

Lamon-Fava, S; Fisher, E C; Nelson, M E; Evans, W J; Millar, J S; Ordovas, J M; Schaefer, E J

1989-01-01

Habitual physical exercise has been reported to have beneficial effects on plasma lipoproteins. To examine this question in women, plasma cholesterol, triglyceride, and apolipoprotein (apo) A-I and B levels, and low density lipoprotein (LDL) particle size were determined in 25 women runners (9 of whom had exercise-related secondary amenorrhea) and 36 age-matched nonexercising women (controls). The eumenorrheic runners had significantly lower apo B levels and significantly greater mean apo A-I/apo B ratios and LDL particle sizes than did the control women (P less than 0.05). Lower apo B levels were correlated with decreased body mass index, a known exercise effect (P less than 0.0001). In addition, normally menstruating runners had cholesterol and triglyceride levels that were 7.6% and 25.4% lower, respectively, and apo A-I levels that were 6.4% higher than control women (P = NS). In amenorrheic runners all parameters were similar to values in control women, except that apo B levels were 20% lower (P less than 0.05). Amenorrheic runners had lower plasma apo A-I levels (13%) and significantly lower apo A-I/apo B ratios and estradiol levels than eumenorrheic runners, and serum estradiol values in the runners were correlated with apo A-I levels (P less than 0.01). These data indicate that the beneficial effects of strenuous exercise on plasma apo A-I levels and apo A-I/apo B ratios in women runners can be reversed by exercise-induced amenorrhea and decreased serum estradiol levels, and that women runners have lower apo B levels than nonexercising women, regardless of menstrual status.

Bounded Rationality in Individual Decision Making

OpenAIRE

Camerer, Colin F.

1998-01-01

The main objectives of this paper are: (i) To give a pithy, opinionated summary of what has been learned about bounded rationality in individual decision making from experiments in economics and psychology (drawing on my 1995 Handbook of Experimental Economics chapter); and (ii) mention some promising new directions for research which would be included if that chapter were written today.

Putative apolipoprotein A-I, natural killer cell enhancement factor and lysozyme g are involved in the early immune response of brown-marbled grouper, Epinephelus fuscoguttatus, Forskal, to Vibrio alginolyticus.

Science.gov (United States)

Low, C-F; Shamsudin, M N; Chee, H-Y; Aliyu-Paiko, M; Idrus, E S

2014-08-01

The gram-negative bacterium, Vibrio alginolyticus, has frequently been identified as the pathogen responsible for the infectious disease called vibriosis. This disease is one of the major challenges facing brown-marbled grouper aquaculture, causing fish farmers globally to suffer substantial economic losses. The objective of this study was to investigate the proteins involved in the immune response of brown-marbled grouper fingerlings during their initial encounter with pathogenic organisms. To achieve this objective, a challenge experiment was performed, in which healthy brown-marbled grouper fingerlings were divided into two groups. Fish in the treated group were subjected to intraperitoneal injection with an infectious dose of V. alginolyticus suspended in phosphate-buffered saline (PBS), and those in the control group were injected with an equal volume of PBS. Blood samples were collected from a replicate number of fish from both groups at 4 h post-challenge and analysed for immune response-related serum proteins via two-dimensional gel electrophoresis. The results showed that 14 protein spots were altered between the treated and control groups; these protein spots were further analysed to determine the identity of each protein via MALDI-TOF/TOF. Among the altered proteins, three were clearly overexpressed in the treated group compared with the control; these were identified as putative apolipoprotein A-I, natural killer cell enhancement factor and lysozyme g. Based on these results, these three highly expressed proteins participate in immune response-related reactions during the initial exposure (4 h) of brown-marbled grouper fingerling to V. alginolyticus infection. © 2013 John Wiley & Sons Ltd.

A priori bounds for solutions of two-point boundary value problems using differential inequalities

International Nuclear Information System (INIS)

Vidossich, G.

1979-01-01

Two point boundary value problems for systems of differential equations are studied with a new approach based on differential inequalities of first order. This leads to the following results: (i) one-sided conditions are enough, in the sense that the inner product is substituted to the norm; (ii) the upper bound exists for practically any kind of equations and boundary value problem if the interval is sufficiently small since it depends on the Peano existence theorem; (iii) the bound seems convenient when the equation has some singularity in t as well as when sigular problems are considered. (author)

Apolipoprotein B levels, APOB alleles, and risk of ischemic cardiovascular disease in the general population, a review

DEFF Research Database (Denmark)

Benn, Marianne

2009-01-01

capturing the entire variation in APOB cannot be identified, and thus most polymorphisms must be evaluated separately in association studies; (3) APOB mutations and polymorphisms are associated with a range of apolipoprotein B and LDL cholesterol levels, although the magnitude of effect sizes of common...... for the E4154K polymorphism that possibly predicts a reduction in risk of ischemic cerebrovascular disease and ischemic stroke, common APOB polymorphisms with modest effect sizes on lipid levels do not predict risk of ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease...

Bound states in weakly disordered spin ladders

Energy Technology Data Exchange (ETDEWEB)

Arlego, M. [Departamento de Fisica, Universidad Nacional de La Plata, CC 67 (1900) La Plata (Argentina)]. E-mail: arlego@venus.fisica.unlp.edu.ar; Brenig, W. [Institut fuer Theoretische Physik, Technische Universitaet Braunschweig (Germany); Cabra, D.C. [Laboratoire de Physique Theorique, Universite Louis Pasteur Strasbourg (France); Heidrich-Meisner, F. [Institut fuer Theoretische Physik, Technische Universitaet Braunschweig (Germany); Honecker, A. [Institut fuer Theoretische Physik, Technische Universitaet Braunschweig (Germany); Rossini, G. [Departamento de Fisica, Universidad Nacional de La Plata, CC 67 (1900) La Plata (Argentina)

2005-04-30

We study the appearance of bound states in the spin gap of spin-12 ladders induced by weak bond disorder. Starting from the strong-coupling limit, i.e., the limit of weakly coupled dimers, we perform a projection on the single-triplet subspace and derive the position of bound states for the single impurity problem of one modified coupling as well as for small impurity clusters. The case of a finite concentration of impurities is treated with the coherent-potential approximation (CPA) in the strong-coupling limit and compared with numerical results. Further, we analyze the details in the structure of the density of states and relate their origin to the influence of impurity clusters.

Virial Expansion Bounds

Science.gov (United States)

Tate, Stephen James

2013-10-01

In the 1960s, the technique of using cluster expansion bounds in order to achieve bounds on the virial expansion was developed by Lebowitz and Penrose (J. Math. Phys. 5:841, 1964) and Ruelle (Statistical Mechanics: Rigorous Results. Benjamin, Elmsford, 1969). This technique is generalised to more recent cluster expansion bounds by Poghosyan and Ueltschi (J. Math. Phys. 50:053509, 2009), which are related to the work of Procacci (J. Stat. Phys. 129:171, 2007) and the tree-graph identity, detailed by Brydges (Phénomènes Critiques, Systèmes Aléatoires, Théories de Jauge. Les Houches 1984, pp. 129-183, 1986). The bounds achieved by Lebowitz and Penrose can also be sharpened by doing the actual optimisation and achieving expressions in terms of the Lambert W-function. The different bound from the cluster expansion shows some improvements for bounds on the convergence of the virial expansion in the case of positive potentials, which are allowed to have a hard core.

Upper bounds on superpartner masses from upper bounds on the Higgs boson mass.

Science.gov (United States)

Cabrera, M E; Casas, J A; Delgado, A

2012-01-13

The LHC is putting bounds on the Higgs boson mass. In this Letter we use those bounds to constrain the minimal supersymmetric standard model (MSSM) parameter space using the fact that, in supersymmetry, the Higgs mass is a function of the masses of sparticles, and therefore an upper bound on the Higgs mass translates into an upper bound for the masses for superpartners. We show that, although current bounds do not constrain the MSSM parameter space from above, once the Higgs mass bound improves big regions of this parameter space will be excluded, putting upper bounds on supersymmetry (SUSY) masses. On the other hand, for the case of split-SUSY we show that, for moderate or large tanβ, the present bounds on the Higgs mass imply that the common mass for scalars cannot be greater than 10(11)  GeV. We show how these bounds will evolve as LHC continues to improve the limits on the Higgs mass.

Frames of exponentials:lower frame bounds for finite subfamilies, and approximation of the inverse frame operator

DEFF Research Database (Denmark)

Christensen, Ole; Lindner, Alexander M

2001-01-01

We give lower frame bounds for finite subfamilies of a frame of exponentials {e(i lambdak(.))}k is an element ofZ in L-2(-pi,pi). We also present a method for approximation of the inverse frame operator corresponding to {e(i lambdak(.))}k is an element ofZ, where knowledge of the frame bounds for...

Identification of peptides from foot‐and‐mouth disease virus structural proteins bound by class I swine leukocyte antigen (SLA) alleles, SLA‐1*0401 and SLA‐2*0401

DEFF Research Database (Denmark)

Pedersen, Lasse Eggers; Harndahl, M.; Nielsen, Morten

2013-01-01

within the structural proteins of foot‐and‐mouth disease virus (FMDV), strain A24 were analyzed as candidate T‐cell epitopes. Peptides predicted by the NetMHCpan were tested in ELISA for binding to the SLA‐1*0401 and SLA‐2*0401 major histocompatibility complex class I proteins. Four of the 10 predicted...... FMDV peptides bound to SLA‐2*0401, whereas five of the nine predicted FMDV peptides bound to SLA‐1*0401. These methods provide the characterization of T‐cell epitopes in response to pathogens in more detail. The development of such approaches to analyze vaccine performance will contribute to a more...

Organically bound tritium

International Nuclear Information System (INIS)

Diabate, S.; Strack, S.

1993-01-01

Tritium released into the environment may be incorporated into organic matter. Organically bound tritium in that case will show retention times in organisms that are considerably longer than those of tritiated water which has significant consequences on dose estimates. This article reviews the most important processes of organically bound tritium production and transport through food networks. Metabolic reactions in plant and animal organisms with tritiated water as a reaction partner are of great importance in this respect. The most important production process, in quantitative terms, is photosynthesis in green plants. The translocation of organically bound tritium from the leaves to edible parts of crop plants should be considered in models of organically bound tritium behavior. Organically bound tritium enters the human body on several pathways, either from the primary producers (vegetable food) or at a higher tropic level (animal food). Animal experiments have shown that the dose due to ingestion of organically bound tritium can be up to twice as high as a comparable intake of tritiated water in gaseous or liquid form. In the environment, organically bound tritium in plants and animals is often found to have higher specific tritium concentrations than tissue water. This is not due to some tritium enrichment effects but to the fact that no equilibrium conditions are reached under natural conditions. 66 refs

Physical Uncertainty Bounds (PUB)

Energy Technology Data Exchange (ETDEWEB)

Vaughan, Diane Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Dean L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2015-03-19

This paper introduces and motivates the need for a new methodology for determining upper bounds on the uncertainties in simulations of engineered systems due to limited fidelity in the composite continuum-level physics models needed to simulate the systems. We show that traditional uncertainty quantification methods provide, at best, a lower bound on this uncertainty. We propose to obtain bounds on the simulation uncertainties by first determining bounds on the physical quantities or processes relevant to system performance. By bounding these physics processes, as opposed to carrying out statistical analyses of the parameter sets of specific physics models or simply switching out the available physics models, one can obtain upper bounds on the uncertainties in simulated quantities of interest.

A geometric bound on F-term inflation

NARCIS (Netherlands)

Borghese, Andrea; Roest, Diederik; Zavala, Ivonne

We discuss a general bound on the possibility to realise inflation in any minimal supergravity with F-terms. The derivation crucially depends on the sGoldstini, the scalar field directions that are singled out by spontaneous supersymmetry breaking. The resulting bound involves both slow-roll

LOCALIZATION OF POLYSOME-BOUND ALBUMIN AND SERINE DEHYDRATASE IN RAT LIVER CELL FRACTIONS

Science.gov (United States)

Ikehara, Yukio; Pitot, Henry C.

1973-01-01

The polysomes involved in albumin and serine dehydratase synthesis were identified and localized by the binding to rat liver polysomes of anti-rat serum albumin and anti-serine dehydratase [125I]Fab dimer and monomer. Techniques were developed for the isolation of undegraded free and membrane-bound polysomes and for the preparation of [125I]Fab monomers and dimers from the IgG obtained from the antisera to the two proteins, rat serum albumin and serine dehydratase. The distribution of anti-rat serum albumin [125I]Fab dimer in the polysome profile is in accordance with the size of polysomes that are expected to be synthesizing albumin. By direct precipitation, it has been demonstrated that nascent chains isolated from the membrane-bound polysomes by puromycin were precipitated by anti-rat serum albumin-IgG at a level of 5–6 times those released from free polysomes. Anti-rat serum albumin-[125I]Fab dimer reacted with membrane-bound polysomes almost exclusively compared to the binding of nonimmune, control [125I]Fab dimer; a significant degree of binding of anti-rat serum albumin-[125I]Fab to free polysomes was also obtained. The [125I]Fab dimer made from normal control rabbit serum does not react with polysomes from liver at all and this preparation will not interact with polysomes extracted from tissues that do not synthesize rat serum albumin. Both anti-serine dehydratase-[125I]Fab monomer and dimer react with free and bound polysomes from livers of animals fed a chow diet or those fed a high 90% protein diet and given glucagon. In the latter instance, however, it is clear that the majority of the binding occurs to the bound polysomes. Furthermore, the specificity of this reaction may be further shown by the use of kidney polysomes that do not normally synthesize serine dehydratase. When these latter polysomes are isolated, even after the addition of crude and purified serine dehydratase, no reaction with anti-serine dehydratase-Fab fragments could be

Generalization bounds of ERM-based learning processes for continuous-time Markov chains.

Science.gov (United States)

Zhang, Chao; Tao, Dacheng

2012-12-01

Many existing results on statistical learning theory are based on the assumption that samples are independently and identically distributed (i.i.d.). However, the assumption of i.i.d. samples is not suitable for practical application to problems in which samples are time dependent. In this paper, we are mainly concerned with the empirical risk minimization (ERM) based learning process for time-dependent samples drawn from a continuous-time Markov chain. This learning process covers many kinds of practical applications, e.g., the prediction for a time series and the estimation of channel state information. Thus, it is significant to study its theoretical properties including the generalization bound, the asymptotic convergence, and the rate of convergence. It is noteworthy that, since samples are time dependent in this learning process, the concerns of this paper cannot (at least straightforwardly) be addressed by existing methods developed under the sample i.i.d. assumption. We first develop a deviation inequality for a sequence of time-dependent samples drawn from a continuous-time Markov chain and present a symmetrization inequality for such a sequence. By using the resultant deviation inequality and symmetrization inequality, we then obtain the generalization bounds of the ERM-based learning process for time-dependent samples drawn from a continuous-time Markov chain. Finally, based on the resultant generalization bounds, we analyze the asymptotic convergence and the rate of convergence of the learning process.

Glucose Regulates the Expression of the Apolipoprotein A5 Gene

Energy Technology Data Exchange (ETDEWEB)

Fruchart, Jamila; Nowak, Maxime; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Moitrot, Emmanuelle; Rommens, Corinne; Pennacchio, Len A.; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

2008-04-07

The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.

High-salt diet combined with elevated angiotensin II accelerates atherosclerosis in apolipoprotein E-deficient mice

DEFF Research Database (Denmark)

Johansson, Maria E; Bernberg, Evelina; Andersson, Irene J

2009-01-01

to atherosclerosis. METHODS: Apolipoprotein E-deficient (ApoE-/-) mice received standard or high-salt diet (8%) alone or in combination with fixed angiotensin II (Ang II) infusion (0.5 microg/kg per min). BP was measured using telemetry, and plaque burden was assessed in the thoracic aorta and innominate artery. We...

Uniform sparse bounds for discrete quadratic phase Hilbert transforms

Science.gov (United States)

Kesler, Robert; Arias, Darío Mena

2017-09-01

For each α \\in T consider the discrete quadratic phase Hilbert transform acting on finitely supported functions f : Z → C according to H^{α }f(n):= \\sum _{m ≠ 0} e^{iα m^2} f(n - m)/m. We prove that, uniformly in α \\in T , there is a sparse bound for the bilinear form for every pair of finitely supported functions f,g : Z→ C . The sparse bound implies several mapping properties such as weighted inequalities in an intersection of Muckenhoupt and reverse Hölder classes.

Upper bound on compositeness scale from strong CP violation

International Nuclear Information System (INIS)

Nelson, A.; Stanford Univ., CA

1988-01-01

In this letter I estimate the size of corrections to the neutron electric dipole moment in composite-technicolor models. The natural size of the electric dipole moment is about 10 -25 e cm (f/3.5 TeV) 24 , where f is the compositeness scale. The current experimental bound of 1.2x10 -25 e cm on the electric dipole moment of the neutron provides an upper bound on the compositeness scale of 3.5 TeV. (orig.)

Bound entangled states violate a nonsymmetric local uncertainty relation

International Nuclear Information System (INIS)

Hofmann, Holger F.

2003-01-01

As a consequence of having a positive partial transpose, bound entangled states lack many of the properties otherwise associated with entanglement. It is therefore interesting to identify properties that distinguish bound entangled states from separable states. In this paper, it is shown that some bound entangled states violate a nonsymmetric class of local uncertainty relations [H. F. Hofmann and S. Takeuchi, Phys. Rev. A 68, 032103 (2003)]. This result indicates that the asymmetry of nonclassical correlations may be a characteristic feature of bound entanglement

[Fundamental evaluation of apolipoprotein B-48 by chemiluminescence enzyme immunoassay--identification of apolipoprotein B-48 with immunoblotting].

Science.gov (United States)

Sato, Itsuko; Fujioka, Yoshio; Hayashi, Fujio; Mukai, Masahiko; Kawano, Seiji; Ishikawa, Yuichi; Yamashita, Shizuya; Kumagai, Shunichi

2007-06-01

Apolipoprotein B-48 (apo B-48) is a constituent of chylomicrons and chylomicron remnants, and its fasting concentration has been reported to be a marker of postprandial hyperlipidemia, which is thought to be a risk factor of atherosclerosis. We evaluated the serum apo B-48 concentrations by chemiluminescence enzyme immunoassay (CLEIA), which was recently introduced as Lumipulse f fully automated immunosaasy analyzer by Fujirebio Inc (Tokyo, Japan), and performed immunoblotting on agarose gel electrophoresis with anti-apo B-48 antibody. Apo B-48 assay was intra-assay reproducible (CVs: 1.9-3.1%) and inter-assay reproducible (CVs: 2.2-4.4%). The assay range for apo B-48 was from 0.2 to 40.0 microg/ml. The effects of interfering substances such as free/conjugated birirubin, hemoglobin, Intrafat, ascorbic acid and rheumatoid factor were negligible. For storage, it was preferable to freeze, and to avoid frozen-thaw process as much as possible. Anti-apo B-48 antibody was reactive over a wide range from origin to the position of very-low-density lipoproteins in immunoblotting after agarose gel electrophoresis. Apo B-48 measurement by CLEIA was feasible to clinical use for the assessment of lipoprotein metabolism.

Universal bounds on current fluctuations.

Science.gov (United States)

Pietzonka, Patrick; Barato, Andre C; Seifert, Udo

2016-05-01

For current fluctuations in nonequilibrium steady states of Markovian processes, we derive four different universal bounds valid beyond the Gaussian regime. Different variants of these bounds apply to either the entropy change or any individual current, e.g., the rate of substrate consumption in a chemical reaction or the electron current in an electronic device. The bounds vary with respect to their degree of universality and tightness. A universal parabolic bound on the generating function of an arbitrary current depends solely on the average entropy production. A second, stronger bound requires knowledge both of the thermodynamic forces that drive the system and of the topology of the network of states. These two bounds are conjectures based on extensive numerics. An exponential bound that depends only on the average entropy production and the average number of transitions per time is rigorously proved. This bound has no obvious relation to the parabolic bound but it is typically tighter further away from equilibrium. An asymptotic bound that depends on the specific transition rates and becomes tight for large fluctuations is also derived. This bound allows for the prediction of the asymptotic growth of the generating function. Even though our results are restricted to networks with a finite number of states, we show that the parabolic bound is also valid for three paradigmatic examples of driven diffusive systems for which the generating function can be calculated using the additivity principle. Our bounds provide a general class of constraints for nonequilibrium systems.

REE bound proteins in natural plant fern Dicranopteris dichitoma by MAA

International Nuclear Information System (INIS)

Guo, F.Q.; Wang, Y.Q.; Sun, J.X.; Chen, H.M.

1996-01-01

Biochemical techniques, including pH variation, outsalting, ultracentrifugation, gel filtration chromatography and electrophoresis, etc., have been employed together with instrumental neutron activation analysis (INAA) to study the rare earth elements (REE) bound proteins in the natural plant fern, Dicranopteris dichitoma. INAA was also used to identify whether the proteins were bound firmly with REE. The results obtained show that two REE bound proteins (RBP-I and RBP-II) have been separated. The molecular weight of RBP-I on Sephadex G-200 gel column is about 8 x 10 5 Daltons and that of RBP-II is less than 12,400 Daltons, respectively. However, SDS-PAGE of the two proteins shows that they mainly have two protein subunits with MW 14,100 and 38,700 Daltons. They are probably conjugated proteins, glycoproteins with different glyco-units. (author). 22 refs., 7 figs., 1 tab

Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

Energy Technology Data Exchange (ETDEWEB)

Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

1994-09-15

Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs

DEFF Research Database (Denmark)

Shim, Jeong; Poulsen, Christian Bo; Hagensen, Mette K.

2017-01-01

Summary: Deficiency of apolipoprotein E (APOE) causes familial dysbetalipoproteinemia in humans resulting in a higher risk of atherosclerotic disease. In mice, APOE deficiency results in a severe atherosclerosis phenotype, but it is unknown to what extent this is unique to mice. In this study, AP...

Efficiency bounds for nonequilibrium heat engines

International Nuclear Information System (INIS)

Mehta, Pankaj; Polkovnikov, Anatoli

2013-01-01

We analyze the efficiency of thermal engines (either quantum or classical) working with a single heat reservoir like an atmosphere. The engine first gets an energy intake, which can be done in an arbitrary nonequilibrium way e.g. combustion of fuel. Then the engine performs the work and returns to the initial state. We distinguish two general classes of engines where the working body first equilibrates within itself and then performs the work (ergodic engine) or when it performs the work before equilibrating (non-ergodic engine). We show that in both cases the second law of thermodynamics limits their efficiency. For ergodic engines we find a rigorous upper bound for the efficiency, which is strictly smaller than the equivalent Carnot efficiency. I.e. the Carnot efficiency can be never achieved in single reservoir heat engines. For non-ergodic engines the efficiency can be higher and can exceed the equilibrium Carnot bound. By extending the fundamental thermodynamic relation to nonequilibrium processes, we find a rigorous thermodynamic bound for the efficiency of both ergodic and non-ergodic engines and show that it is given by the relative entropy of the nonequilibrium and initial equilibrium distributions. These results suggest a new general strategy for designing more efficient engines. We illustrate our ideas by using simple examples. -- Highlights: ► Derived efficiency bounds for heat engines working with a single reservoir. ► Analyzed both ergodic and non-ergodic engines. ► Showed that non-ergodic engines can be more efficient. ► Extended fundamental thermodynamic relation to arbitrary nonequilibrium processes

Effects of dietary saturated fat on LDL subclasses and apolipoprotein CIII in men

OpenAIRE

Faghihnia, Nastaran; Mangravite, Lara M.; Chiu, Sally; Bergeron, Nathalie; Krauss, Ronald M.

2012-01-01

Background/Objectives Small dense LDL particles and apolipoprotein (apo) CIII are risk factors for cardiovascular disease (CVD) that can be modulated by diet, but there is little information regarding the effects of dietary saturated fat on their plasma levels. We tested the effects of high vs. low saturated fat intake in the context of a high beef protein diet on levels and composition of LDL subclasses and on apoCIII levels in plasma and LDL. Subjects/Methods Following consumption of a base...

Association of Apolipoprotein B and Adiponectin Receptor 1 Genes with Carcass, Bone Integrity and Performance Traits in a Paternal Broiler Line.

Directory of Open Access Journals (Sweden)

Valdecy Aparecida Rocha da Cruz

Full Text Available Apolipoprotein B (APOB and Adiponectin Receptor 1 (ADIPOR1 are related to the regulation of feed intake, fat metabolism and protein deposition and are candidate genes for genomic studies in birds. In this study, associations of two single nucleotide polymorphisms (SNPs g.102A>T (APOB and g.729C>T (ADIPOR1 with carcass, bone integrity and performance traits in broilers were investigated. Genotyping was performed on a paternal line of 1,454 broilers. The SNP detection was carried out by PCR-RFLP technique using the restriction enzymes HhaI for the SNP g.729C>T and MslI for the SNP g.102A>T. The association analyses of the two SNPs with 85 traits were performed using the restricted maximum likelihood (REML and Generalized Quasi-Likelihood Score (GQLS methods. For REML the model included the random additive genetic effect of animal and fixed effects of sex, hatch and SNP genotypes. In the GQLS method, a logistic regression was used to associate the genotypes with phenotypes adjusted for fixed effects of sex and hatch. The SNP g.729C>T in the ADIPOR1 gene was associated with thickness of the femur and breast skin yield. Thus, the ADIPOR1 gene seems implicated in the metabolism and/or fat deposition and bone integrity in broilers.

Pricing summer day options by good-deal bounds

International Nuclear Information System (INIS)

Kanamura, Takashi; Ohashi, Kazuhiko

2009-01-01

Despite the worldwide popularity of CDD- and HDD-type weather derivatives based on temperature, a different class of weather derivatives, so-called summer day options, is more popular in Japan; the payoffs are determined by the number of summer days (i.e., the days whose average temperature is above 25 C) during the contract period. In this paper, we price such summer day options by the good-deal bounds of Cochrane and Saa-Requejo [Cochrane, J.H., and J. Saa-Requejo, 2000, Beyond Arbitrage: Good-Deal Asset Price Bounds in Incomplete Markets, Journal of Political Economy 108, 79-119.], using temperature data for Tokyo. (author)

78 FR 18326 - Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math...

Science.gov (United States)

2013-03-26

...; Comment Request; Upward Bound and Upward Bound Math Science Annual Performance Report AGENCY: The Office... considered public records. Title of Collection: Upward Bound and Upward Bound Math Science Annual Performance...) and Upward Bound Math and Science (UBMS) Programs. The Department is requesting a new APR because of...

Spectral bounds for the PT-breaking Hamiltonian p2 + x4 + iax

International Nuclear Information System (INIS)

Handy, C R; Wang Xiaoqian

2003-01-01

The non-Hermitian Hamiltonian p 2 + x 4 + iax, which spontaneously breaks PT-symmetry, and the subject of a recent study by Bender et al (2001 J. Phys. A: Math. Gen. 34 L31), is amenable to a positivity representation, facilitating the generation of converging bounds to the complex-eigenenergies of the PT-breaking states. This system is much easier (i.e. fewer variational parameters) than the previously studied case of the Hamiltonian p 2 + ix 3 + iax (2001 Handy J. Phys. A: Math. Gen. 34 5065, Handy et al 2001 J. Phys. A: Math. Gen. 34 5593), as first proposed by Delabaere and Trinh (2000 J. Phys. A: Math. Gen. 33 8771), enabling the generation of low order algebraic spectral bounds (i.e. Re(E) > 81/4 (Im(E)/a) 4 + O(a 2 )), in addition to high order, numerically generated, converging bounds to the discrete states. We examine both approaches here

Contribution of granule bound starch synthase in kernel modification ...

African Journals Online (AJOL)

The role of gbssI and gbssII genes, encoding granule bound starch synthase enzyme I and II, respectively, in quality protein maize (QPM) were studied at different days after pollination (DAP). Total RNA was used for first strand cDNA synthesis using the ImpromIISriptTM reverse transcriptase. No detectable levels of gbssI ...

Population genetics of apolipoprotein A-4, E, and H polymorphisms in Yanomami Indians of northwestern Brazil: associations with lipids, lipoproteins, and carbohydrate metabolism.

Science.gov (United States)

Crews, D E; Kamboh, M I; Mancilha-Carvalho, J J; Kottke, B

1993-04-01

Using isoelectric focusing and immunoblotting techniques, we screened 96 serum samples from Yanomami Indians of northwestern Brazil to determine structural variation at three apolipoprotein loci: A4, E, and H. The APO-H locus, which is commonly polymorphic in white and black samples, was found to be monomorphic. At the APO-E locus only two alleles, APOE*3 and APOE*4, rather than the three-allele polymorphism commonly seen in Caucasians, was observed. At the APO-A4 locus no example of the APOA4*2 allele, found in Caucasians, was detected. However, the frequency of the less common APOA4*4 allele was above what has been observed in any other population. We investigated the impact of genetic variation at both polymorphic loci on quantitative differences in lipids, apolipoproteins, serum glucose, glycated hemoglobin, and uric acid. Contrary to the cholesterol-elevating effect of APOE*4 reported elsewhere, in both univariate analyses and after adjustments for age, sex, weight, and height, APOE*4 was associated with about a 4% lower mean serum cholesterol. Only after adjustment was this association statistically significant. The APOE*4 allele was significantly associated with unadjusted APO-A1 and APO-E levels but not with any other dependent variable; associations with adjusted APO-A1, APO-C2, and uric acid also approached standard levels of statistical significance (p < or = 0.05). In univariate analyses the APOA4*4 allele was significantly associated with APO-B, serum glucose, percent glycated hemoglobin, and uric acid, but no significant associations were observed after dependent variables were adjusted for age, sex, weight, and height. These results support the notion that apolipoprotein distributions and their associations with lipid and carbohydrate metabolism show ethnic variability.

Production of recombinant cholesterol oxidase containing covalently bound FAD in Escherichia coli

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Molla Gianluca

2010-04-01

Full Text Available Abstract Background Cholesterol oxidase is an alcohol dehydrogenase/oxidase flavoprotein that catalyzes the dehydrogenation of C(3-OH of cholesterol. It has two major biotechnological applications, i.e. in the determination of serum (and food cholesterol levels and as biocatalyst providing valuable intermediates for industrial steroid drug production. Cholesterol oxidases of type I are those containing the FAD cofactor tightly but not covalently bound to the protein moiety, whereas type II members contain covalently bound FAD. This is the first report on the over-expression in Escherichia coli of type II cholesterol oxidase from Brevibacterium sterolicum (BCO. Results Design of the plasmid construct encoding the mature BCO, optimization of medium composition and identification of the best cultivation/induction conditions for growing and expressing the active protein in recombinant E. coli cells, concurred to achieve a valuable improvement: BCO volumetric productivity was increased from ~500 up to ~25000 U/L and its crude extract specific activity from 0.5 up to 7.0 U/mg protein. Interestingly, under optimal expression conditions, nearly 55% of the soluble recombinant BCO is produced as covalently FAD bound form, whereas the protein containing non-covalently bound FAD is preferentially accumulated in insoluble inclusion bodies. Conclusions Comparison of our results with those published on non-covalent (type I COs expressed in recombinant form (either in E. coli or Streptomyces spp., shows that the fully active type II BCO can be produced in E. coli at valuable expression levels. The improved over-production of the FAD-bound cholesterol oxidase will support its development as a novel biotool to be exploited in biotechnological applications.

Lipid profiles reflecting high and low risk for coronary heart disease : Contribution of apolipoprotein E polymorphism and lifestyle

NARCIS (Netherlands)

Boer, J.M.A.; Feskens, E.J.M.; Schouten, E.G.; Havekes, L.M.; Seidell, J.C.; Kromhout, D.

1998-01-01

To elucidate the role of modifiable factors and the apolipoprotein E polymorphism in explaining lipid profiles reflecting low, average and high risk for coronary heart disease, we selected subjects from a large population-based study. Subjects with low total cholesterol (TC) (< 15th percentile) and

Lipid profiles reflecting high and low risk for coronary heart disease: contribution of apolipoprotein E polymorphism and lifestyle.

NARCIS (Netherlands)

Boer, J.M.A.; Feskens, E.J.M.; Schouten, E.G.; Havekes, L.M.; Seidell, J.C.; Kromhout, D.

1998-01-01

To elucidate the role of modifiable factors and the apolipoprotein E polymorphism in explaining lipid profiles reflecting low, average and high risk for coronary heart disease, we selected subjects from a large population-based study. Subjects with low total cholesterol (TC) (<15th percentile)

Culture-Bound Words of the Danube Basin Countries: Translation into English

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Chetverikova Olena

2015-08-01

Full Text Available Any course in linguistic country study or popular text translation is impossible without adequate understanding and presentation of culture-bound elements, which present one of the most difficult topics to deal with, especially in multicultural countries. Our investigation aims to show the problems, which appear when we deal with equivalent-lacking words related to culture. Sometimes equivalent-lacking words are associated with culture-bound words, the Ukrainian equivalent for them is “реалії” (derived from Latin realis, pl. realia. However, the term “culture-bound word” is of narrower meaning than the term “equivalent-lacking word”. A culture-bound word names an object peculiar to this or that ethnic culture. Equivalent-lacking words include, along with culture-bound words, neologisms, i.e. newly coined forms, dialect words, slang, taboo-words, foreign (third language terms, proper names, misspellings, archaisms. Comparison of languages and cultures reveals the various types of culture-bound words. Reasons for using them can be extralinguistic, lexical or stylistic. When translating culture-bound words a translator should be aware of the receptor’s potential problems, take into account his background knowledge and choose the best means of translation.

Quivers of Bound Path Algebras and Bound Path Coalgebras

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Dr. Intan Muchtadi

2010-09-01

Full Text Available bras and coalgebras can be represented as quiver (directed graph, and from quiver we can construct algebras and coalgebras called path algebras and path coalgebras. In this paper we show that the quiver of a bound path coalgebra (resp. algebra is the dual quiver of its bound path algebra (resp. coalgebra.

Regulation of the Apolipoprotein Gene Cluster by a Long Noncoding RNA

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Paul Halley

2014-01-01

Full Text Available Apolipoprotein A1 (APOA1 is the major protein component of high-density lipoprotein (HDL in plasma. We have identified an endogenously expressed long noncoding natural antisense transcript, APOA1-AS, which acts as a negative transcriptional regulator of APOA1 both in vitro and in vivo. Inhibition of APOA1-AS in cultured cells resulted in the increased expression of APOA1 and two neighboring genes in the APO cluster. Chromatin immunoprecipitation (ChIP analyses of a ∼50 kb chromatin region flanking the APOA1 gene demonstrated that APOA1-AS can modulate distinct histone methylation patterns that mark active and/or inactive gene expression through the recruitment of histone-modifying enzymes. Targeting APOA1-AS with short antisense oligonucleotides also enhanced APOA1 expression in both human and monkey liver cells and induced an increase in hepatic RNA and protein expression in African green monkeys. Furthermore, the results presented here highlight the significant local modulatory effects of long noncoding antisense RNAs and demonstrate the therapeutic potential of manipulating the expression of these transcripts both in vitro and in vivo.

Scaling Limits and Generic Bounds for Exploration Processes

Science.gov (United States)

Bermolen, Paola; Jonckheere, Matthieu; Sanders, Jaron

2017-12-01

We consider exploration algorithms of the random sequential adsorption type both for homogeneous random graphs and random geometric graphs based on spatial Poisson processes. At each step, a vertex of the graph becomes active and its neighboring nodes become blocked. Given an initial number of vertices N growing to infinity, we study statistical properties of the proportion of explored (active or blocked) nodes in time using scaling limits. We obtain exact limits for homogeneous graphs and prove an explicit central limit theorem for the final proportion of active nodes, known as the jamming constant, through a diffusion approximation for the exploration process which can be described as a unidimensional process. We then focus on bounding the trajectories of such exploration processes on random geometric graphs, i.e., random sequential adsorption. As opposed to exploration processes on homogeneous random graphs, these do not allow for such a dimensional reduction. Instead we derive a fundamental relationship between the number of explored nodes and the discovered volume in the spatial process, and we obtain generic bounds for the fluid limit and jamming constant: bounds that are independent of the dimension of space and the detailed shape of the volume associated to the discovered node. Lastly, using coupling techinques, we give trajectorial interpretations of the generic bounds.

A gauged baby Skyrme model and a novel BPS bound

International Nuclear Information System (INIS)

Adam, C; Naya, C; Sanchez-Guillen, J; Wereszczynski, A

2013-01-01

The baby Skyrme model is a well-known nonlinear field theory supporting topological solitons in two space dimensions. Its action functional consist of a potential term, a kinetic term quadratic in derivatives (the 'nonlinear sigma model term') and the Skyrme term quartic in first derivatives. The limiting case of vanishing sigma model term (the so-called BPS baby Skyrme model) is known to support exact soliton solutions saturating a BPS bound which exists for this model. Further, the BPS model has infinitely many symmetries and conservation laws. Recently it was found that the gauged version of the BPS baby Skyrme model with gauge group U(1) and the usual Maxwell term, too, has a BPS bound and BPS solutions saturating this bound. This BPS bound is determined by a superpotential which has to obey a superpotential equation, in close analogy to the situation in supergravity. Further, the BPS bound and the corresponding BPS solitons only may exist for potentials such that the superpotential equation has a global solution. We also briefly describe some properties of soliton solutions.

Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction

DEFF Research Database (Denmark)

Langsted, A.; Freiberg, J.J.; Nordestgaard, Børge

2008-01-01

BACKGROUND: Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events. METHODS AND RESULTS: We cross-sectionally studied 33 391 individuals 20 to 95...... to HDL cholesterol, and ratio of apolipoprotein B to apolipoprotein A1 did not change in response to normal food intake. The maximum changes after normal food and fluid intake from fasting levels were -0.2 mmol/L for total cholesterol, -0.2 mmol/L for low-density lipoprotein cholesterol, -0.1 mmol...... years of age from the Copenhagen General Population Study. We also studied 9319 individuals 20 to 93 years of age from the Copenhagen City Heart Study, 1166 of whom developed cardiovascular events during 14 years of follow-up. Compared with fasting levels, total cholesterol, low-density lipoprotein...

Development of CER-001: Preclinical Dose Selection Through to Phase I Clinical Findings.

Science.gov (United States)

Keyserling, Constance H; Barbaras, Ronald; Benghozi, Renee; Dasseux, Jean-Louis

2017-05-01

CER-001 comprises recombinant human apolipoprotein A-I complexed with phospholipids that mimics natural, nascent, pre-β high-density lipoprotein (HDL). We present animal model data showing dose-dependent increases in cholesterol efflux with CER-001 and its subsequent elimination by reverse lipid transport, together with inhibition of atherosclerotic plaque progression. We report the first phase I study results with CER-001 in humans, starting at 0.25 mg/kg, which is 1/80th of the safe dose (20 mg/kg) established in 4-week multiple-dose animal studies dosed every second day. Healthy volunteers, 18-55 years old with a low-density lipoprotein-cholesterol:HDL-cholesterol ratio greater than 3.0, received single intravenous escalating doses of CER-001 (0.25-45.0 mg/kg) and placebo in a double-blind randomised cross-over fashion. Subjects were followed up for 3 weeks post-dose. Assessments included adverse event monitoring, blood sampling, and clinical laboratory measurements. Thirty-two subjects were enrolled. All CER-001 doses (0.25-45 mg/kg) were safe and well tolerated, with an adverse event profile similar to placebo. Effects on clinical chemistry, haematology and coagulation parameters were comparable to placebo. No adverse effects of CER-001 on electrocardiograms were observed. No antibodies to apolipoprotein A-I were detected following single-dose administration of CER-001. Plasma apolipoprotein A-I levels increased in a dose-related manner and returned to baseline by 24 h post-dose for doses up to 10 mg/kg but remained in circulation for >72 h post-dose for doses >10 mg/kg. CER-001 caused elevations in plasma cholesterol and total and unesterified cholesterol in the HDL fraction. Mobilisation of unesterified cholesterol in the HDL fraction was seen with CER-001 at doses as low as 2 mg/kg. CER-001 is well tolerated when administered to humans as single doses up to 45 mg/kg and mobilises and eliminates cholesterol via reverse lipid transport.

Entanglement detection with bounded reference frames

International Nuclear Information System (INIS)

Costa, Fabio; Brukner, Caslav; Harrigan, Nicholas; Rudolph, Terry

2009-01-01

Quantum experiments usually assume the existence of perfect, classical reference frames (RFs), which allow for the specification of measurement settings (e.g. orientation of the Stern-Gerlach magnet in spin measurements) with arbitrary precision. If the RFs are 'bounded' (i.e. quantum systems themselves, having a finite number of degrees of freedom), only limited precision can be attained. Using spin coherent states as bounded RFs, we have found the minimum size needed for them to violate local realism for entangled spin systems. For composite systems of spin 1/2 particles, RFs of very small size are sufficient for the violation; however, to see this violation for macroscopic entangled spins, the size of the RF must be at least quadratically larger than that of the spins. The unavailability of such RFs gives a possible explanation for the non-observance of violation of local realism in everyday experience.

Cooperative unfolding of apolipoprotein A-1 induced by chemical denaturation.

Science.gov (United States)

Eckhardt, D; Li-Blatter, X; Schönfeld, H-J; Heerklotz, H; Seelig, J

2018-05-25

Apolipoprotein A-1 (Apo A-1) plays an important role in lipid transfer and obesity. Chemical unfolding of α-helical Apo A-1 is induced with guanidineHCl and monitored with differential scanning calorimetry (DSC) and CD spectroscopy. The unfolding enthalpy and the midpoint temperature of unfolding decrease linearly with increasing guanidineHCl concentration, caused by the weak binding of denaturant. At room temperature, binding of 50-60 molecules guanidineHCl leads to a complete Apo A-1 unfolding. The entropy of unfolding decreases to a lesser extent than the unfolding enthalpy. Apo A-1 chemical unfolding is a dynamic multi-state equilibrium that is analysed with the Zimm-Bragg theory modified for chemical unfolding. The chemical Zimm-Bragg theory predicts the denaturant binding constant K D and the protein cooperativity σ. Chemical unfolding of Apo A-1 is two orders of magnitude less cooperative than thermal unfolding. The free energy of thermal unfolding is ~0.2 kcal/mol per amino acid residue and ~1.0 kcal/mol for chemical unfolding at room temperature. The Zimm-Bragg theory calculates conformational probabilities and the chemical Zimm-Bragg theory predicts stretches of α-helical segments in dynamic equilibrium, unfolding and refolding independently and fast. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Photon virtual bound state

International Nuclear Information System (INIS)

Inoue, J.; Ohtaka, K.

2004-01-01

We study virtual bound states in photonics, which are a vectorial extension of electron virtual bound states. The condition for these states is derived. It is found that the Mie resonant state which satisfies the condition that the size parameter is less than the angular momentum should be interpreted as a photon virtual bound state. In order to confirm the validity of the concept, we compare the photonic density of states, the width of which represents the lifetime of the photon virtual bound states, with numerical results

Apolipoprotein J (clusterin) and Alzheimer's disease.

Science.gov (United States)

Calero, M; Rostagno, A; Matsubara, E; Zlokovic, B; Frangione, B; Ghiso, J

2000-08-15

Apolipoprotein J (clusterin) is a ubiquitous multifunctional glycoprotein capable of interacting with a broad spectrum of molecules. In pathological conditions, it is an amyloid associated protein, co-localizing with fibrillar deposits in systemic and localized amyloid disorders. In Alzheimer's disease, the most frequent form of amyloidosis in humans and the major cause of dementia in the elderly, apoJ is present in amyloid plaques and cerebrovascular deposits but is rarely seen in NFT-containing neurons. ApoJ expression is up-regulated in a wide variety of insults and may represent a defense response against local damage to neurons. Four different mechanisms of action could be postulated to explain the role of apoJ as a neuroprotectant during cellular stress: (1) function as an anti-apoptotic signal, (2) protection against oxidative stress, (3) inhibition of the membrane attack complex of complement proteins locally activated as a result of inflammation, and (4) binding to hydrophobic regions of partially unfolded, stressed proteins, and therefore avoiding aggregation in a chaperone-like manner. This review focuses on the association of apoJ in biological fluids with Alzheimer's soluble Abeta. This interaction prevents Abeta aggregation and fibrillization and modulates its blood-brain barrier transport at the cerebrovascular endothelium. Copyright 2000 Wiley-Liss, Inc.

On devising Boussinesq-type models with bounded eigenspectra: One horizontal dimension

DEFF Research Database (Denmark)

Eskilsson, Claes; Engsig-Karup, Allan Peter

2014-01-01

) are introduced. Using spectral element simulations of stream function waves it is illustrated that (i) the bounded equations capture the physics of the wave motion as well as the standard unbounded equations, and (ii) the bounded equations are computationally more efficient when explicit time-stepping schemes...... using a spectral element method of arbitrary spatial order p. It is shown that existing sets of parameters, found by optimising the linear dispersion relation, give rise to unbounded eigenspectra which govern stability. For explicit time-stepping schemes the global CFL time-step restriction typically...... requires Δt∝p−2. We derive and present conditions on the parameters under which implicitly-implicit Boussinesq-type equations will exhibit bounded eigenspectra. Two new bounded versions having comparable nonlinear and dispersive properties as the equations of Nwogu (1993) and Schäffer and Madsen (1995...

BanII dimorphic site located in the third intron of the human apolipoprotein AI (APOA1) gene

Energy Technology Data Exchange (ETDEWEB)

Coleman, R T; Kresnak, M T; Frossard, P M

1988-02-11

A 0.7kb fragment generated by AvaII digestion of pBL13AI, a 0.965kb full-length human apolipoprotein AI cDNA was cloned into the EcoRI site of pBR322. The apoAI cDNA was isolated from a lambdagt10 human fetal liver cDNA library. BanII (GPuGCPyC) (International Biotechnologies, Inc.) identifies two invariant bands at 1122bp and 417bp, and a single two-allele polymorphism with bands at either 274bp or 452bp. The human apolipoprotein AI-CIII-AIV gene complex has been localized on the long arm of chromosome 11 by Southern blot analysis of human-chinese hamster cell hybrids. Co-dominant segregation has been observed in two families (13 individuals). The BanII restriction map was constructed from DNA sequence data of the human apoAI gene. The 452bp fragment is generated by the loss of a BanII dimorphic site in the third intron of the apoAI gene, between the 178bp and the 274bp fragments.

Apolipoprotein A5: A newly identified gene impacting plasmatriglyceride levels in humans and mice

Energy Technology Data Exchange (ETDEWEB)

Pennacchio, Len A.; Rubin, Edward M.

2002-09-15

Apolipoprotein A5 (APOA5) is a newly described member of theapolipoprotein gene family whose initial discovery arose from comparativesequence analysis of the mammalian APOA1/C3/A4 gene cluster. Functionalstudies in mice indicated that alteration in the level of APOA5significantly impacted plasma triglyceride concentrations. Miceover-expressing human APOA5 displayed significantly reducedtriglycerides, while mice lacking apoA5 had a large increase in thislipid parameter. Studies in humans have also suggested an important rolefor APOA5 in determining plasma triglyceride concentrations. In theseexperiments, polymorphisms in the human gene were found to define severalcommon haplotypes that were associated with significant changes intriglyceride concentrations in multiple populations. Several separateclinical studies have provided consistent and strong support for theeffect with 24 percent of Caucasians, 35 percent of African-Americans and53 percent of Hispanics carrying APOA5 haplotypes associated withincreased plasma triglyceride levels. In summary, APOA5 represents anewly discovered gene involved in triglyceride metabolism in both humansand mice whose mechanism of action remains to be deciphered.

Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA

DEFF Research Database (Denmark)

Andersen, Christian Brix Folsted; Ballut, Lionel; Johansen, Jesper Sanderhoff

2006-01-01

exon junction core complex containing the DEAD-box adenosine triphosphatase (ATPase) eukaryotic initiation factor 4AIII (eIF4AIII) bound to an ATP analog, MAGOH, Y14, a fragment of MLN51, and a polyuracil mRNA mimic. eIF4AIII interacts with the phosphate-ribose backbone of six consecutive nucleotides...... and prevents part of the bound RNA from being double stranded. The MAGOH and Y14 subunits lock eIF4AIII in a prehydrolysis state, and activation of the ATPase probably requires only modest conformational changes in eIF4AIII motif I....

Structures of holo wild-type human cellular retinol-binding protein II (hCRBPII) bound to retinol and retinal.

Science.gov (United States)

Nossoni, Zahra; Assar, Zahra; Yapici, Ipek; Nosrati, Meisam; Wang, Wenjing; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James

2014-12-01

Cellular retinol-binding proteins (CRBPs) I and II, which are members of the intracellular lipid-binding protein (iLBP) family, are retinoid chaperones that are responsible for the intracellular transport and delivery of both retinol and retinal. Although structures of retinol-bound CRBPI and CRBPII are known, no structure of a retinal-bound CRBP has been reported. In addition, the retinol-bound human CRBPII (hCRBPII) structure shows partial occupancy of a noncanonical conformation of retinol in the binding pocket. Here, the structure of retinal-bound hCRBPII and the structure of retinol-bound hCRBPII with retinol fully occupying the binding pocket are reported. It is further shown that the retinoid derivative seen in both the zebrafish CRBP and the hCRBPII structures is likely to be the product of flux-dependent and wavelength-dependent X-ray damage during data collection. The structures of retinoid-bound CRBPs are compared and contrasted, and rationales for the differences in binding affinities for retinal and retinol are provided.

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

Directory of Open Access Journals (Sweden)

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.

The transport of triglycerides through the secretory pathway of hepatocytes is impaired in apolipoprotein E deficient mice.

NARCIS (Netherlands)

Mensenkamp, A.R.; Luyn, M.J.A. van; Havinga, R.; Teusink, B.; Waterman, I.J.; Mann, C.J.; Elzinga, B.M.; Verkade, H.J.; Zammit, V.A.; Havekes, L.M.; Shoulders, C.C.; Kuipers, F.

2004-01-01

BACKGROUND/AIMS: Apolipoprotein E (apoE)-deficient mice develop hepatic steatosis and secrete reduced levels of VLDL-TG. METHODS AND RESULTS: We examined the effects of apoE-deficiency on intracellular lipid homeostasis and secretion of triglycerides (TG). We show that intracellular TG turnover and

The transport of triglycerides through the secretory pathway of hepatocytes is impaired in apolipoprotein E deficient mice

NARCIS (Netherlands)

Mensenkamp, AR; van Luyn, MJA; Havinga, R; Teusink, B; Waterman, IJ; Mann, CJ; Elzinga, BM; Verkade, HJ; Zammit, VA; Havekes, LM; Shoulders, CC; Kuipers, F

Background/Aims: Apolipoprotein E (apoE)-deficient mice develop hepatic steatosis and secrete reduced levels of VLDL-TG. Methods and results: We examined the effects of apoE-deficiency on intracellular lipid homeostasis and secretion of triglycerides (TG). We show that intracellular TG turnover and

Bound-state quark and gluon contributions to structure functions in QCD

International Nuclear Information System (INIS)

Brodsky, S.J.

1991-01-01

One can distinguish two types of contributions to the quark and gluon structure functions of hadrons in quantum chromodynamics: 'intrinsic' contributions, which are due to the direct scattering on the bound-state constituents, and 'extrinsic' contributions, which are derived from particles created in the collision. In this talk, I discuss several aspects of deep inealstic structure functions in which the bound-state structure of the proton plays a crucial role: (1) the properties of the intrinsic gluon distribution associated with the proton bound-state wavefunction; (2) the separation of the quark structure function of the proton into intrinsic 'bound-valence' and extrinsic 'non-valence' components which takes into account the Pauli principle; (3) the properties and identification of intrinsic heavy quark structure functions; and (4) a theory of shadowing and anti-shadowing of nuclear structure functions, directly related to quark-nucleon interactions and the gluon saturation phenomenon. (orig.)

Bound-state quark and gluon contributions to structure functions in QCD

International Nuclear Information System (INIS)

Brodsky, S.J.

1990-08-01

One can distinguish two types of contributions to the quark and gluon structure functions of hadrons in quantum chromodynamics: ''intrinsic'' contributions, which are due to the direct scattering on the bound-state constituents, and ''extrinsic'' contributions, which are derived from particles created in the collision. In this talk, I discussed several aspects of deep inelastic structure functions in which the bound-state structure of the proton plays a crucial role: the properties of the intrinsic gluon distribution associated with the proton bound-state wavefunction; the separation of the quark structure function of the proton onto intrinsic ''bound-valence'' and extrinsic ''non-valence'' components which takes into account the Pauli principle; the properties and identification of intrinsic heavy quark structure functions; and a theory of shadowing and anti-shadowing of nuclear structure functions, directly related to quark-nucleon interactions and the gluon saturation phenomenon. 49 refs., 5 figs

Apolipoprotein E-epsilon 4 frequency in affective disorder

DEFF Research Database (Denmark)

Kessing, L V; Jørgensen, O S

1999-01-01

-Bråne-Steen Dementia Rating Scale, and the Global Deterioration Scale. RESULTS: The frequency of APOE-epsilon 4 allele was approximately the same in unipolar patients (.189) and in bipolar patients (.167). Although patients showed more cognitive impairment than controls, no significant overall difference was found...... was found with gender, age at onset, the number of affective episodes, the presence of psychotic features, or the prevalence of familial affective disorder. CONCLUSIONS: It seems that cognitive impairment in affective disorder can be attributed to pathways other than the APOE genotype.......BACKGROUND: The epsilon 4 allele of apolipoprotein E (APOE) as well as affective disorder have been found to be associated with Alzheimer's disease, but it is unclear whether cognitive impairment in affective disorder or subtypes of affective disorder is mediated by the epsilon 4 allele of APOE...

Function and Comorbidities of Apolipoprotein E in Alzheimer's Disease

Directory of Open Access Journals (Sweden)

Valérie Leduc

2011-01-01

Full Text Available Alzheimer's disease (AD—the most common type of dementia among the elderly—represents one of the most challenging and urgent medical mysteries affecting our aging population. Although dominant inherited mutation in genes involved in the amyloid metabolism can elicit familial AD, the overwhelming majority of AD cases, dubbed sporadic AD, do not display this Mendelian inheritance pattern. Apolipoprotein E (APOE, the main lipid carrier protein in the central nervous system, is the only gene that has been robustly and consistently associated with AD risk. The purpose of the current paper is thus to highlight the pleiotropic roles and the structure-function relationship of APOE to stimulate both the functional characterization and the identification of novel lipid homeostasis-related molecular targets involved in AD.

Preoperative apolipoprotein CI levels correlate positively with the proinflammatory response in patients experiencing endotoxemia following elective cardiac surgery

NARCIS (Netherlands)

Schippers, E.F.; Berbée, J.F.P.; Disseldorp, I.M. van; Versteegh, M.I.M.; Havekes, L.M.; Rensen, P.C.N.; Dissel, J.T. van

2008-01-01

Objective: Experimental models show that apolipoprotein CI (apoCI) binds and enhances the inflammatory response to endotoxin. We studied in patients undergoing cardiopulmonary bypass surgery (CPB) and experiencing endotoxemia during reperfusion whether plasma apoCI levels correlate with the

Relation between plasma and brain lipids

DEFF Research Database (Denmark)

Wellington, Cheryl L; Frikke-Schmidt, Ruth

2016-01-01

: Plasma levels of traditional lipids and lipoproteins are not consistently associated with risk of dementia even though low plasma levels of apolipoprotein E, through unknown mechanisms, robustly predict future dementia. Experimental evidence suggests neuroprotective roles of several brain...... and cerebrospinal fluid apolipoproteins. Whether plasma levels of apolipoprotein E, or any other apolipoprotein with possible central nervous system and/or blood-brain barrier functions (apolipoproteins J, A-I, A-II, A-IV, D, C-I, and C-III) may become accessible biomarker components that improve risk prediction...

Proteomic Profile of Unstable Atheroma Plaque: Increased Neutrophil Defensin 1, Clusterin, and Apolipoprotein E Levels in Carotid Secretome.

Science.gov (United States)

Aragonès, Gemma; Auguet, Teresa; Guiu-Jurado, Esther; Berlanga, Alba; Curriu, Marta; Martinez, Salomé; Alibalic, Ajla; Aguilar, Carmen; Hernández, Esteban; Camara, María-Luisa; Canela, Núria; Herrero, Pol; Ruyra, Xavier; Martín-Paredero, Vicente; Richart, Cristóbal

2016-03-04

Because of the clinical significance of carotid atherosclerosis, the search for novel biomarkers has become a priority. The aim of the present study was to compare the protein secretion profile of the carotid atherosclerotic plaque (CAP, n = 12) and nonatherosclerotic mammary artery (MA, n = 10) secretomes. We used a nontargeted proteomic approach that incorporated tandem immunoaffinity depletion, iTRAQ labeling, and nanoflow liquid chromatography coupled to high-resolution mass spectrometry. In total, 162 proteins were quantified, of which 25 showed statistically significant differences in secretome levels between carotid atherosclerotic plaque and nondiseased mammary artery. We found increased levels of neutrophil defensin 1, apolipoprotein E, clusterin, and zinc-alpha-2-glycoprotein in CAP secretomes. Results were validated by ELISA assays. Also, differentially secreted proteins are involved in pathways such as focal adhesion and leukocyte transendothelial migration. In conclusion, this study provides a subset of identified proteins that are differently expressed in secretomes of clinical significance.

Number theoretic methods in cryptography complexity lower bounds

CERN Document Server

Shparlinski, Igor

1999-01-01

The book introduces new techniques which imply rigorous lower bounds on the complexity of some number theoretic and cryptographic problems. These methods and techniques are based on bounds of character sums and numbers of solutions of some polynomial equations over finite fields and residue rings. It also contains a number of open problems and proposals for further research. We obtain several lower bounds, exponential in terms of logp, on the de­ grees and orders of • polynomials; • algebraic functions; • Boolean functions; • linear recurring sequences; coinciding with values of the discrete logarithm modulo a prime p at suf­ ficiently many points (the number of points can be as small as pI/He). These functions are considered over the residue ring modulo p and over the residue ring modulo an arbitrary divisor d of p - 1. The case of d = 2 is of special interest since it corresponds to the representation of the right­ most bit of the discrete logarithm and defines whether the argument is a quadratic...

Simple bounds for counting processes with monotone rate of occurrence of failures

International Nuclear Information System (INIS)

Kaminskiy, Mark P.

2007-01-01

The article discusses some aspects of analogy between certain classes of distributions used as models for time to failure of nonrepairable objects, and the counting processes used as models for failure process for repairable objects. The notion of quantiles for the counting processes with strictly increasing cumulative intensity function is introduced. The classes of counting processes with increasing (decreasing) rate of occurrence of failures are considered. For these classes, the useful nonparametric bounds for cumulative intensity function based on one known quantile are obtained. These bounds, which can be used for repairable objects, are similar to the bounds introduced by Barlow and Marshall [Barlow, R. Marshall, A. Bounds for distributions with monotone hazard rate, I and II. Ann Math Stat 1964; 35: 1234-74] for IFRA (DFRA) time to failure distributions applicable to nonrepairable objects

Apolipoprotein M in lipid metabolism and cardiometabolic diseases

DEFF Research Database (Denmark)

Borup, Anna; Christensen, Pernille Meyer; Nielsen, Lars B.

2015-01-01

: The apoM/S1P axis and its implications in atherosclerosis and lipid metabolism have been thoroughly studied. Owing to the discovery of the apoM/S1P axis, the scope of apoM research has broadened. ApoM and S1P have been implicated in lipid metabolism, that is by modulating HDL particles. Also......PURPOSE: This review will address recent findings on apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) in lipid metabolism and inflammatory diseases. RECENT FINDINGS: ApoM's likely role(s) in health and disease has become more diverse after the discovery that apoM functions...... as a chaperone for S1P. Hence, apoM has recently been implicated in lipid metabolism, diabetes and rheumatoid arthritis through in-vivo, in-vitro and genetic association studies. It remains to be established to which degree such associations with apoM can be attributed to its ability to bind S1P. SUMMARY...

Evaluation of Apolipoprotein A5 Polymorphism in Coronary- Heart Disease Patients

Directory of Open Access Journals (Sweden)

Somayeh Haqparast

2012-02-01

Full Text Available Background and Objectives: Apolipoprotein A5 (APOA5 gene is important in determining plasma triglyceride levels, a major cardiovascular disease risk factor. Mutation in this gene affected plasma triglyceride level. We looked for possible associations of the APOA5 gene polymorphism S19W with coronary heart disease (CHD in a sample of Iranian population. Materials and Methods: A total of 73 CHD patients and 55 controls were genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP for this single nucleotide polymorphism. Serum lipids and Fast Blood Sugar concentrations were measured in all subjects with enzymatic method. Results: Allele frequencies observed in our population were 0.041 for the W allele and 0.959 for the S allele which are similar to other populations (p>0.05. There is no evidence that APOA5 S19W, is a risk factor of CHD in our sample (p>0.05. In addition, we observed no association between the APOA5 W allele and elevated plasma TG levels (p>0.05 in the CHD group. This result was also present in the control group (p>0.05. Conclusion: The APO A5 gene polymorphism in S19W gene has no association with the high susceptibility to CHD.

The interplay of intrinsic and extrinsic bounded noises in biomolecular networks.

Directory of Open Access Journals (Sweden)

Giulio Caravagna

Full Text Available After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a biomolecular network. The influence of intrinsic and extrinsic noises on biomolecular networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: (i the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, (ii a model of enzymatic futile cycle and (iii a genetic toggle switch. In (ii and (iii we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possible functional role of bounded noises.

The interplay of intrinsic and extrinsic bounded noises in biomolecular networks.

Science.gov (United States)

Caravagna, Giulio; Mauri, Giancarlo; d'Onofrio, Alberto

2013-01-01

After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a biomolecular network. The influence of intrinsic and extrinsic noises on biomolecular networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: (i) the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, (ii) a model of enzymatic futile cycle and (iii) a genetic toggle switch. In (ii) and (iii) we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possible functional role of bounded noises.

Apolipoprotein E Genotype and educational attainment predict the rate of cognitive decline in normal aging? A 12-year follow-up of the Maastricht Aging Study

NARCIS (Netherlands)

van Gerven, P.W.; van Boxtel, M.P.J.; Bekers, O.; Ausems, E.E.B.; Jolles, J.

2012-01-01

Objective: We investigated suspected longitudinal interaction effects of apolipoprotein E (APOE) genotype and educational attainment on cognitive decline in normal aging. Method: Our sample consisted of 571 healthy, nondemented adults aged between 49 and 82 years. Linear mixed-models analyses were

Curvature bound from gravitational catalysis

Science.gov (United States)

Gies, Holger; Martini, Riccardo

2018-04-01

We determine bounds on the curvature of local patches of spacetime from the requirement of intact long-range chiral symmetry. The bounds arise from a scale-dependent analysis of gravitational catalysis and its influence on the effective potential for the chiral order parameter, as induced by fermionic fluctuations on a curved spacetime with local hyperbolic properties. The bound is expressed in terms of the local curvature scalar measured in units of a gauge-invariant coarse-graining scale. We argue that any effective field theory of quantum gravity obeying this curvature bound is safe from chiral symmetry breaking through gravitational catalysis and thus compatible with the simultaneous existence of chiral fermions in the low-energy spectrum. With increasing number of dimensions, the curvature bound in terms of the hyperbolic scale parameter becomes stronger. Applying the curvature bound to the asymptotic safety scenario for quantum gravity in four spacetime dimensions translates into bounds on the matter content of particle physics models.

Study on REE bound proteins in natural plant fern dicranopteris dichotomy by MAA

International Nuclear Information System (INIS)

Guo Fanqing; Wang Yuqi; Sun Jingxing; Chen Hongmin; Xu Lei; Cao Guoyin

1997-01-01

Biochemical techniques, including pH variation, outsalting, ultracentrifugation, gel filtration chromatography and electrophoresis, etc., have been employed together with instrumental neutron activation analysis (INAA) to study the rare earth elements (REE) bound proteins in the natural plant fern, Dicranopteris dichotomy. INAA was also used to identify whether the proteins were bound firmly with REE. The results obtained show that two REE bound proteins (RBP-I and RBP-II) have been separated. The molecular mass (molecular weight, MW) of RBP-I on Sephadex G-200 gel column is about 8 x 10 5 and that of RBP-II is less than 12400, respectively. However, SDS-PAGE of the two proteins shows that they mainly have two protein subunits with MW 14100 and 38700. They are probably conjugated proteins, glycoproteins with different glycol-units

Σ hypernuclear bound state observed in stopped K- reaction on 4He

International Nuclear Information System (INIS)

Hayano, R.S.; Ishikawa, T.; Iwasaki, M.; Outa, H.; Takada, E.; Tamura, H.; Sakaguchi, A.; Aoki, M.; Yamazaki, T.

1988-12-01

Results are presented of inclusive measurements of π ± momentum spectra from K - absorption at rest in liquid helium. We found a peak in the π - spectrum. The (K - , π + ) spectrum does not exhibit a clear peak in the Σ - bound region. Comparison of these two spectra suggests that the peak in the π - spectrum is due to the formation of the S = 0, I = 1/2 ground state of Σ-nucleus bound state. (J.P.N.)

A high-fat meal promotes lipid-load and apolipoprotein B-48 receptor transcriptional activity in circulating monocytes.

Science.gov (United States)

Varela, Lourdes M; Ortega, Almudena; Bermudez, Beatriz; Lopez, Sergio; Pacheco, Yolanda M; Villar, Jose; Abia, Rocio; Muriana, Francisco J G

2011-05-01

The postprandial metabolism of dietary fats results in the production of apolipoprotein B-48 (apoB48)-containing triglyceride-rich lipoproteins (TRLs), which cause rapid receptor-mediated macrophage lipid engorgement via the apoB48 cell surface receptor (apoB48R). Monocytes circulate together with apoB48-containing TRLs in the postprandial bloodstream and may start accumulating lipids even before their migration to tissues and differentiation to macrophages. We sought to determine whether circulating monocytes are equipped with apoB48R and whether, in the postprandial state, circulating monocytes accumulate lipids and modulate apoB48R transcriptional activity after intake of a high-fat meal. In a crossover design, we studied the effect of a high-fat meal on fasting and postprandial concentrations of triglycerides, free fatty acids, cholesterol, and insulin in 12 healthy men. TRLs and monocytes were freshly isolated at fasting, hourly until the postprandial peak, and at the late postprandial phase. TRLs were subjected to triglycerides, apoB48, and apolipoprotein B-100 analyses; and lipid accumulation and apoB48R mRNA expression levels were measured in monocytes. Monocytes showed a time-dependent lipid accumulation in response to the high-fat meal, which was paralleled by an increase in apoB48R mRNA expression levels. These effects were coincident only with an increase in apoB48-containing TRLs in the postprandial phase and were also observed ex vivo in freshly isolated monocytes incubated with apoB48-containing TRLs. In a setting of abundant plasma apoB48-containing TRLs, these findings highlight the role of dietary fat in inducing lipid accumulation and apoB48R gene transcription in circulating monocytes.

Roles of high apolipoprotein E blood levels and HDL in development of familial dysbetalipoproteinemia in ε2ε2 subjects

NARCIS (Netherlands)

Corsetti, James P; Sparks, Charles E; Bakker, Stephan J L; Gruppen, Eke G; Dullaart, Robin P F

2017-01-01

OBJECTIVE: Familial dysbetalipoproteinemia (FD) or Type III hyperlipoproteinemia is a mixed hyperlipidemia closely associated with the ε2ε2 genotype of the common APOE polymorphism although not all homozygotes progress to FD. Unlike the polymorphism, few studies explore effects of apolipoprotein E

Apolipoprotein E (APOE) ε4 and episodic memory decline in Alzheimer's disease: A review.

Science.gov (United States)

El Haj, Mohamad; Antoine, Pascal; Amouyel, Philippe; Lambert, Jean-Charles; Pasquier, Florence; Kapogiannis, Dimitrios

2016-05-01

A growing body of research has examined the relationship between episodic memory decline, the cognitive hallmark of Alzheimer's disease (AD), and the presence of Apolipoprotein E ε4 (APOE ε4) allele, a major genetic risk factor for the disease. Our review attempts to summarize and critically evaluate this literature. We performed a systematic search for studies assessing episodic memory in AD patients who were genotyped for APOE ε4 and identified fourteen papers. Although most of these papers reported significant relationships between APOE ε4 and episodic memory decline in AD, some papers did not confirm this relationship. Our review links this controversy to the conflicting literature about the effects of APOE ε4 on general cognitive functioning in AD. We identify several shortcoming and limitations of the research on the relationship between APOE ε4 and episodic memory in AD, such as small sample sizes, non-representative populations, lack of comparison of early-onset vs. late-onset disease, and lack of comparison among different genotypes that include APOE ε4 (i.e., zero, one, or two ε4 alleles). Another major shortcoming of the reviewed literature was the lack of comprehensive evaluation of episodic memory decline, since episodic memory was solely evaluated with regard to encoding and retrieval, omitting evaluation of core episodic features that decline in AD, such as context recall (e.g., how, where, and when an episodic event has occurred) and subjective experience of remembering (e.g., reliving, emotion and feeling during episodic recollection). Future research taking these limitations into consideration could illuminate the nature of the relationship between APOE ε4 and episodic memory decline in AD. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanism of lipid lowering in mice expressing human apolipoprotein A5

Energy Technology Data Exchange (ETDEWEB)

Fruchart-Najib, Jamila; Bauge, Eric; Niculescu, Loredan-Stefan; Pham, Tatiana; Thomas, Benoit; Rommens, Corinne; Majd, Zouher; Brewer, Bryan; Rubin, Edward M.; Pennacchio, Len A.; Fruchart, Jean-Charles

2004-01-15

Recently, we reported that apoAV plays key role in triglycerides lowering. Here, we attempted to determine the mechanism underlying this hypotriglyceridemic effect. We showed that triglyceride turnover is faster in hAPOA5 transgenic compared to wild type mice. Moreover, both apoB and apoCIII are decreased and LPL activity is increased in postheparin plasma of hAPOA5 transgenic mice. These data suggest a decrease in size and number of VLDL. To further investigate the mechanism of hAPOA5 in hyperlipidemic background, we intercrossed hAPOA5 and hAPOC3 transgenic mice. The effect resulted in a marked decreased of VLDL triglyceride, cholesterol, apolipoproteins B and CIII. In postprandial state, the triglyceride response is abolished in hAPOA5 transgenic mice. We demonstrated that in response to the fat load in hAPOA5XhAPOC3 mice, apoAV shifted from HDL to VLDL, probably to limit the elevation of triglycerides. In vitro, apoAV activates lipoprotein lipase. However, apoAV does not interact with LPL but interacts physically with apoCIII. This interaction does not seem to displace apoCIII from VLDL but may induce conformational change in apoCIII and consequently change in its function leading the activation of lipoprotein lipase.

Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin-Induced Spinal Cord Demyelination in Mice

OpenAIRE

Gu, Zhen; Li, Fengqiao; Zhang, Yi Ping; Shields, Lisa B.E.; Hu, Xiaoling; Zheng, Yiyan; Yu, Panpan; Zhang, Yongjie; Cai, Jun; Vitek, Michael P.; Shields, Christopher B.

2014-01-01

Objective Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG1...

Wnt3a nanodisks promote ex vivo expansion of hematopoietic stem and progenitor cells

DEFF Research Database (Denmark)

Lalefar, Nahal R.; Witkowski, Andrzej; Simonsen, Jens Bæk

2016-01-01

Background : Wnt proteins modulate development, stem cell fate and cancer through interactions with cell surface receptors. Wnts are cysteine-rich, glycosylated, lipid modified, two domain proteins that are prone to aggregation. The culprit responsible for this behavior is a covalently bound palm...... to Lin- Sca-1+ c-Kit+ cell expansion, an effect that was not mediated through β-catenin. Conclusions : The data indicate Wnt3a ND constitute a water-soluble transport vehicle capable of promoting ex vivo expansion of HSPC.......Background : Wnt proteins modulate development, stem cell fate and cancer through interactions with cell surface receptors. Wnts are cysteine-rich, glycosylated, lipid modified, two domain proteins that are prone to aggregation. The culprit responsible for this behavior is a covalently bound...... palmitoleoyl moiety in the N-terminal domain. Results : By combining murine Wnt3a with phospholipid and apolipoprotein A-I, ternary complexes termed nanodisks (ND) were generated. ND-associated Wnt3a is soluble in the absence of detergent micelles and gel filtration chromatography revealed that Wnt3a co...

Phosphorylation-dependent down-regulation of apolipoprotein A5 by insulin

Energy Technology Data Exchange (ETDEWEB)

Nowak, Maxine; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Rommens, Corinne; Martin, Genevieve; Duran-Sandoval, Daniel; Staels, Bart; Rubin, Edward M.; Pennacchio, Len A.; Taskinen, Marja-Riitta; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

2004-02-15

The apolipoprotein A5 (APOA5) gene has been shown to be important in lowering plasma triglyceride levels. Since several studies have shown that hyperinsulinemia is associated with hypertriglyceridemia, we sought to determine whether APOA5 gene is regulated by insulin. We show here that cell and mouse treatments with insulin down-regulated APOA5 expression in a dose-dependent manner. Furthermore, we determined that insulin decreases APOA5 promoter activity and subsequent deletion analyses revealed an E-box-containing fragment. We showed that Upstream Stimulatory Factors, USF1/USF2, bind to the identified E-box in the APOA5 promoter. Moreover, in cotransfection studies, USF1 stimulates APOA5 promoter activity. The treatment with insulin reduces the binding of USF1/USF2 to APOA5 promoter. The inhibition of PI3K pathway with wortmannin abolished the insulin s effect on APOA5 gene transcription. Using oligoprecipitation method of USF from nuclear extracts, we demonstrated that phosphorylated USF1 failed to bind to APOA5 promoter. This indicates that the APOA5 gene transrepression by insulin involves a phosphorylation of USF through PI3K, that modulate their binding to APOA5 promoter and results in APOA5 down-regulation. The effect of exogenous hyperinsulinemia in healthy men shows a decrease of the plasma ApoAV level. These data suggest a potential mechanism involving APOA5 gene in hypertriglyceridemia associated with hyperinsulinemia.

Improved bounds on the epidemic threshold of exact SIS models on complex networks

KAUST Repository

Ruhi, Navid Azizan; Thrampoulidis, Christos; Hassibi, Babak

2017-01-01

The SIS (susceptible-infected-susceptible) epidemic model on an arbitrary network, without making approximations, is a 2n-state Markov chain with a unique absorbing state (the all-healthy state). This makes analysis of the SIS model and, in particular, determining the threshold of epidemic spread quite challenging. It has been shown that the exact marginal probabilities of infection can be upper bounded by an n-dimensional linear time-invariant system, a consequence of which is that the Markov chain is “fast-mixing” when the LTI system is stable, i.e. when equation (where β is the infection rate per link, δ is the recovery rate, and λmax(A) is the largest eigenvalue of the network's adjacency matrix). This well-known threshold has been recently shown not to be tight in several cases, such as in a star network. In this paper, we provide tighter upper bounds on the exact marginal probabilities of infection, by also taking pairwise infection probabilities into account. Based on this improved bound, we derive tighter eigenvalue conditions that guarantee fast mixing (i.e., logarithmic mixing time) of the chain. We demonstrate the improvement of the threshold condition by comparing the new bound with the known one on various networks with various epidemic parameters.

Improved bounds on the epidemic threshold of exact SIS models on complex networks

KAUST Repository

Ruhi, Navid Azizan

2017-01-05

The SIS (susceptible-infected-susceptible) epidemic model on an arbitrary network, without making approximations, is a 2n-state Markov chain with a unique absorbing state (the all-healthy state). This makes analysis of the SIS model and, in particular, determining the threshold of epidemic spread quite challenging. It has been shown that the exact marginal probabilities of infection can be upper bounded by an n-dimensional linear time-invariant system, a consequence of which is that the Markov chain is “fast-mixing” when the LTI system is stable, i.e. when equation (where β is the infection rate per link, δ is the recovery rate, and λmax(A) is the largest eigenvalue of the network\\'s adjacency matrix). This well-known threshold has been recently shown not to be tight in several cases, such as in a star network. In this paper, we provide tighter upper bounds on the exact marginal probabilities of infection, by also taking pairwise infection probabilities into account. Based on this improved bound, we derive tighter eigenvalue conditions that guarantee fast mixing (i.e., logarithmic mixing time) of the chain. We demonstrate the improvement of the threshold condition by comparing the new bound with the known one on various networks with various epidemic parameters.

Bounding species distribution models

Directory of Open Access Journals (Sweden)

Thomas J. STOHLGREN, Catherine S. JARNEVICH, Wayne E. ESAIAS,Jeffrey T. MORISETTE

2011-10-01

Full Text Available Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for “clamping” model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART and maximum entropy (Maxent models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5: 642–647, 2011].

Bounding Species Distribution Models

Science.gov (United States)

Stohlgren, Thomas J.; Jarnevich, Cahterine S.; Morisette, Jeffrey T.; Esaias, Wayne E.

2011-01-01

Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5): 642-647, 2011].

A note on BPS vortex bound states

Directory of Open Access Journals (Sweden)

A. Alonso-Izquierdo

2016-02-01

Full Text Available In this note we investigate bound states, where scalar and vector bosons are trapped by BPS vortices in the Abelian Higgs model with a critical ratio of the couplings. A class of internal modes of fluctuation around cylindrically symmetric BPS vortices is characterized mathematically, analyzing the spectrum of the second-order fluctuation operator when the Higgs and vector boson masses are equal. A few of these bound states with low values of quantized magnetic flux are described fully, and their main properties are discussed.

A note on BPS vortex bound states

Energy Technology Data Exchange (ETDEWEB)

Alonso-Izquierdo, A., E-mail: alonsoiz@usal.es [Departamento de Matematica Aplicada, Universidad de Salamanca (Spain); Garcia Fuertes, W., E-mail: wifredo@uniovi.es [Departamento de Fisica, Universidad de Oviedo (Spain); Mateos Guilarte, J., E-mail: guilarte@usal.es [Departamento de Fisica Fundamental, Universidad de Salamanca (Spain)

2016-02-10

In this note we investigate bound states, where scalar and vector bosons are trapped by BPS vortices in the Abelian Higgs model with a critical ratio of the couplings. A class of internal modes of fluctuation around cylindrically symmetric BPS vortices is characterized mathematically, analyzing the spectrum of the second-order fluctuation operator when the Higgs and vector boson masses are equal. A few of these bound states with low values of quantized magnetic flux are described fully, and their main properties are discussed.

Lifestyle and Dietary Determinants of Serum Apolipoprotein A1 and Apolipoprotein B Concentrations: Cross-Sectional Analyses within a Swedish Cohort of 24,984 Individuals.

Science.gov (United States)

Frondelius, Kasper; Borg, Madelene; Ericson, Ulrika; Borné, Yan; Melander, Olle; Sonestedt, Emily

2017-02-28

Low serum apolipoprotein (Apo) A1 concentrations and high serum ApoB concentrations may be better markers of the risk of cardiovascular disease than high-density lipoprotein (HDL) and low-density lipoprotein (LDL). However, the associations between modifiable lifestyle factors and Apo concentrations have not been investigated in detail. Therefore, this study investigated the associations between Apo concentrations and education, lifestyle factors and dietary intake (macronutrients and 34 food groups). These cross-sectional associations were examined among 24,984 individuals in a Swedish population-based cohort. Baseline examinations of the cohort were conducted between 1991 and 1996. Dietary intake was assessed using a modified diet history method. The main determinants of high ApoA1 concentrations ( r between 0.05 and 0.25) were high alcohol consumption, high physical activity, non-smoking, and a low body mass index (BMI), and the main determinants of high ApoB concentrations were smoking and a high BMI. The intake of sucrose and food products containing added sugar (such as pastries, sweets, chocolate, jam/sugar and sugar-sweetened beverages) was negatively correlated with ApoA1 concentrations and positively correlated with ApoB concentrations and the ApoB/ApoA1 ratio, whereas the intake of fermented dairy products, such as fermented milk and cheese, was positively correlated with ApoA1 concentrations and negatively correlated with the ApoB/ApoA1 ratio. These results indicate that smoking, obesity, low physical activity, low alcohol consumption and a diet high in sugar and low in fermented dairy products are correlated with an unfavorable Apo profile.

Plasma levels of sphingosine-1-phosphate and apolipoprotein M in patients with monogenic disorders of HDL metabolism

NARCIS (Netherlands)

Karuna, Ratna; Park, Rebekka; Othman, Alaa; Holleboom, Adriaan G.; Motazacker, Mohammad Mahdi; Sutter, Iryna; Kuivenhoven, Jan Albert; Rohrer, Lucia; Matile, Hugues; Hornemann, Thorsten; Stoffel, Markus; Rentsch, Katharina M.; von Eckardstein, Arnold

2011-01-01

Apolipoprotein M (apoM) has been identified as a specific sphingosine-1-phosphate (S1P) binding protein of HDL. To investigate the in vivo effects of disturbed apoM or HDL metabolism we quantified S1P and apoM in plasmas of wild-type, apoM-knock-out, and apoM transgenic mice as well as 50 patients

Deeply bound pionic atom

International Nuclear Information System (INIS)

Toki, Hiroshi; Yamazaki, Toshimitsu

1989-01-01

The standard method of pionic atom formation does not produce deeply bound pionic atoms. A study is made on the properties of deeply bound pionic atom states by using the standard pion-nucleus optical potential. Another study is made to estimate the cross sections of the formation of ls pionic atom states by various methods. The pion-nucleus optical potential is determined by weakly bound pionic atom states and pion nucleus scattering. Although this potential may not be valid for deeply bound pionic atoms, it should provide some hint on binding energies and level widths of deeply bound states. The width of the ls state comes out to be 0.3 MeV and is well separated from the rest. The charge dependence of the ls state is investigated. The binding energies and the widths increase linearly with Z azbove a Z of 30. The report then discusses various methods to populate deeply bound pionic atoms. In particular, 'pion exchange' reactions are proposed. (n, pπ) reaction is discussed first. The cross section is calculated by assuming the in- and out-going nucleons on-shell and the produced pion in (n1) pionic atom states. Then, (n, dπ - ) cross sections are estimated. (p, 2 Heπ - ) reaction would have cross sections similar to the cross section of (n, dπ - ) reaction. In conclusion, it seems best to do (n, p) experiment on heavy nuclei for deeply bound pionic atom. (Nogami, K.)

Crystal structure of Na+, K(+)-ATPase in the Na(+)-bound state.

Science.gov (United States)

Nyblom, Maria; Poulsen, Hanne; Gourdon, Pontus; Reinhard, Linda; Andersson, Magnus; Lindahl, Erik; Fedosova, Natalya; Nissen, Poul

2013-10-04

The Na(+), K(+)-adenosine triphosphatase (ATPase) maintains the electrochemical gradients of Na(+) and K(+) across the plasma membrane--a prerequisite for electrical excitability and secondary transport. Hitherto, structural information has been limited to K(+)-bound or ouabain-blocked forms. We present the crystal structure of a Na(+)-bound Na(+), K(+)-ATPase as determined at 4.3 Å resolution. Compared with the K(+)-bound form, large conformational changes are observed in the α subunit whereas the β and γ subunit structures are maintained. The locations of the three Na(+) sites are indicated with the unique site III at the recently suggested IIIb, as further supported by electrophysiological studies on leak currents. Extracellular release of the third Na(+) from IIIb through IIIa, followed by exchange of Na(+) for K(+) at sites I and II, is suggested.

Effect of tocopherol on atherosclerosis, vascular function, and inflammation in apolipoprotein E knockout mice with subtotal nephrectomy.

Science.gov (United States)

Shing, Cecilia M; Fassett, Robert G; Peake, Jonathan M; Coombes, Jeff S

2014-12-01

Inflammation and endothelial dysfunction contribute to cardiovascular disease, prevalent in chronic kidney disease (CKD). Antioxidant supplements such as tocopherols may reduce inflammation and atherosclerosis. This study aimed to investigate the effect of tocopherol supplementation on vascular function, aortic plaque formation, and inflammation in apolipoprotein E(-/-) mice with 5/6 nephrectomy as a model of combined cardiovascular and kidney disease. Nephrectomized mice were assigned to a normal chow diet group (normal chow), a group receiving 1000 mg/kg diet of α-tocopherol supplementation or a group receiving 1000 mg/kg diet mixed-tocopherol (60% γ-tocopherol). Following 12 weeks, in vitro aortic endothelial-independent relaxation was enhanced with both α-tocopherol and mixed-tocopherol (P tocopherol enhanced aortic contraction at noradrenaline concentrations of 3 × 10(-7) M to 3 × 10(-5) M (P tocopherol reduced systemic concentrations of IL-6 (P tocopherol also reduced MCP-1 (P tocopherol supplementation when compared to normal chow (P Tocopherol supplementation favorably influenced vascular function and cytokine profile, while it was also effective in reducing atherosclerosis in the apolipoprotein E(-/-) mouse with CKD. © 2014 John Wiley & Sons Ltd.

Nonlinear spectroscopy of the bound exciton states in CdSe single crystals

International Nuclear Information System (INIS)

Lisitsa, M.P.; Onishchenko, N.A.; Stolyarenko, A.V.; Ananchenko, V.V.; Polishchuk, S.V.

1989-01-01

The study is devoted to the pulsed laser radiation effect on the time-resolved variations of free and bound exciton bands region at the helium temperature. A gradual disappearance of the bound I 2 exciton state is observed with increase of the excitation intensity I in CdSe transmission spectra. This phenomenon is explained by the fact that despite of the shorter life of I 2 excitons as compared to the free ones, the concentration of the centres on which they localize is rather low (≤10 16 cm -3 ) while the evolution of the light-generated electron-hole pairs is such as the most probable recombination through the bound excitons. The transmission spectrum kinetics is studied. The intensity limitation of the laser pulse transmitted through the crystal in the region of the exciton ground state region is shown to be related with two-photon absorption (TPA) in which the exciton state is an intermediate level. The calculation results are in good agreement with the experiment. The estimations show the giant TPA coefficient of ∼10 3 cm/MW. The evolution of photoexcited nonequilibrium electron-hole pairs is studied. The possibility of using CdSe single crystals as spectrum-selective limiters of the laser pulses is shown. (author)

Discovering the role of the apolipoprotein gene and the genes in the putative pullulan biosynthesis pathway on the synthesis of pullulan, heavy oil and melanin in Aureobasidium pullulans.

Science.gov (United States)

Guo, Jian; Huang, Siyao; Chen, Yefu; Guo, Xuewu; Xiao, Dongguang

2017-12-18

Pullulan produced by Aureobasidium pullulans presents various applications in food manufacturing and pharmaceutical industry. However, the pullulan biosynthesis mechanism remains unclear. This work proposed a pathway suggesting that heavy oil and melanin may correlate with pullulan production. The effects of overexpression or deletion of genes encoding apolipoprotein, UDPG-pyrophosphorylase, glucosyltransferase, and α-phosphoglucose mutase on the production of pullulan, heavy oil, and melanin were examined. Pullulan production increased by 16.93 and 8.52% with the overexpression of UDPG-pyrophosphorylase and apolipoprotein genes, respectively. Nevertheless, the overexpression or deletion of other genes exerted little effect on pullulan biosynthesis. Heavy oil production increased by 146.30, 64.81, and 33.33% with the overexpression of UDPG-pyrophosphorylase, α-phosphoglucose mutase, and apolipoprotein genes, respectively. Furthermore, the syntheses of pullulan, heavy oil, and melanin can compete with one another. This work may provide new guidance to improve the production of pullulan, heavy oil, and melanin through genetic approach.

Distortion-Rate Bounds for Distributed Estimation Using Wireless Sensor Networks

Directory of Open Access Journals (Sweden)

Nihar Jindal

2008-03-01

Full Text Available We deal with centralized and distributed rate-constrained estimation of random signal vectors performed using a network of wireless sensors (encoders communicating with a fusion center (decoder. For this context, we determine lower and upper bounds on the corresponding distortion-rate (D-R function. The nonachievable lower bound is obtained by considering centralized estimation with a single-sensor which has all observation data available, and by determining the associated D-R function in closed-form. Interestingly, this D-R function can be achieved using an estimate first compress afterwards (EC approach, where the sensor (i forms the minimum mean-square error (MMSE estimate for the signal of interest; and (ii optimally (in the MSE sense compresses and transmits it to the FC that reconstructs it. We further derive a novel alternating scheme to numerically determine an achievable upper bound of the D-R function for general distributed estimation using multiple sensors. The proposed algorithm tackles an analytically intractable minimization problem, while it accounts for sensor data correlations. The obtained upper bound is tighter than the one determined by having each sensor performing MSE optimal encoding independently of the others. Numerical examples indicate that the algorithm performs well and yields D-R upper bounds which are relatively tight with respect to analytical alternatives obtained without taking into account the cross-correlations among sensor data.

Labeling schemes for bounded degree graphs

DEFF Research Database (Denmark)

Adjiashvili, David; Rotbart, Noy Galil

2014-01-01

We investigate adjacency labeling schemes for graphs of bounded degree Δ = O(1). In particular, we present an optimal (up to an additive constant) log n + O(1) adjacency labeling scheme for bounded degree trees. The latter scheme is derived from a labeling scheme for bounded degree outerplanar...... graphs. Our results complement a similar bound recently obtained for bounded depth trees [Fraigniaud and Korman, SODA 2010], and may provide new insights for closing the long standing gap for adjacency in trees [Alstrup and Rauhe, FOCS 2002]. We also provide improved labeling schemes for bounded degree...

HDL Subspecies Defined by Presence of Apolipoprotein C-III and Incident Coronary Heart Disease in Four Cohorts

DEFF Research Database (Denmark)

Jensen, Majken K; Aroner, Sarah A; Mukamal, Kenneth J

2018-01-01

Background -The causal role of high density lipoprotein (HDL) cholesterol in cardioprotection has been questioned by genetic and randomized studies. Novel measures that relate to HDL function may contribute new information to prediction of cardiovascular risk. Apolipoprotein C-III (apoC-III) is a......Background -The causal role of high density lipoprotein (HDL) cholesterol in cardioprotection has been questioned by genetic and randomized studies. Novel measures that relate to HDL function may contribute new information to prediction of cardiovascular risk. Apolipoprotein C-III (apo...... studies of adults free of CHD. In the Multi-Ethnic Study of Atherosclerosis (MESA), 5,657 participants (52% women; age 52-72 y) were followed for risk of CHD from 2000-2002 through 2013. In a case-cohort study nested within the Danish Diet, Cancer and Health (DCH) study, 3,642 participants (47% women; age.......87). Conclusions -Our findings from four prospective studies support the hypothesis that apoC-III may mark a subfraction of HDL that is associated with higher risk of CHD. New measures reflecting HDL structure and function may provide novel insights for cardiovascular risk that extend beyond traditional plasma HDL...

Primary Genetic Investigation of a Hyperlipidemia Model: Molecular Characteristics and Variants of the Apolipoprotein E Gene in Mongolian Gerbil

Directory of Open Access Journals (Sweden)

Yuehuan Liu

2014-01-01

Full Text Available The objective of this work was to establish a novel Mongolian gerbil (Meriones unguiculatus hyperlipidemia model and to investigate its susceptibility genetic basis. Two rodent (gerbil and rat hyperlipidemia models were induced by feeding a high fat/high-cholesterol (HF/HC diet. There were significant increases of serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C, and high-density lipoprotein cholesterol (HDL-C in gerbils within a 4-week modeling period. About 10–30% of >8-month-old individuals developed hyperlipidemia spontaneously. The apolipoprotein E (ApoE gene was cloned by merging a sequence of rapid amplification of cDNA ends (RACE and nested polymerase chain reaction products. The results revealed an open reading frame of 948 bp, encoding a protein of 298 amino acids. The gene without a 5′-UTR region in the first intron was highly homologous to human Apo-A-I and rat Apo-A-IV. The distribution of expression of the ApoE gene in liver, brain, heart, lung, kidney, and adrenal gland was detected by an ABC immunohistochemical procedure. Three single nucleotide polymorphisms (SNPs; C97T, G781T, and A1774T were first found using PCR-single-strand conformation polymorphism (PCR-SSCP in a closed population containing 444 animals. Correlation analysis confirmed that new SNPs , age, and gender were associated significantly (P<0.05 with hyperlipidemia.

Scattering by bound nucleons

International Nuclear Information System (INIS)

Tezuka, Hirokazu.

1984-10-01

Scattering of a particle by bound nucleons is discussed. Effects of nucleons that are bound in a nucleus are taken as a structure function. The way how to calculate the structure function is given. (author)

Metabolic hormones, apolipoproteins, adipokines, and cytokines in the alveolar lining fluid of healthy adults: compartmentalization and physiological correlates.

Directory of Open Access Journals (Sweden)

Carlos O Mendivil

Full Text Available Our current understanding of hormone regulation in lung parenchyma is quite limited. We aimed to quantify a diverse array of biologically relevant protein mediators in alveolar lining fluid (ALF, compared to serum concentrations, and explore factors associated with protein compartmentalization on either side of the air-blood barrier.Participants were 24 healthy adult non-smoker volunteers without respiratory symptoms or significant medical conditions, with normal lung exams and office spirometry. Cell-free bronchoalveolar lavage fluid and serum were analyzed for 24 proteins (including enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines using a highly sensitive multiplex ELISA. Measurements were normalized to ALF concentrations. The ALF:serum concentration ratios were examined in relation to measures of protein size, hydrophobicity, charge, and to participant clinical and spirometric values.ALF measurements from 24 individuals detected 19 proteins, including adiponectin, adipsin, apoA-I, apoA-II, apoB, apoC-II, apoC-III, apoE, C-reactive protein, ghrelin, glucose-dependent insulinotropic peptide (GIP, glucagon-like peptide-1 (GLP-1, glucagon, insulin, leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, resistin, and visfatin. C-peptide and serpin E1 were not detected in ALF for any individual, and IL-6, IL-10, and TNF-alpha were not detected in either ALF or serum for any individual. In general, ALF levels were similar or lower in concentration for most proteins compared to serum. However, ghrelin, resistin, insulin, visfatin and GLP-1 had ALF concentrations significantly higher compared to serum. Importantly, elevated ALF:serum ratios of ghrelin, visfatin and resistin correlated with protein net charge and isoelectric point, but not with molecular weight or hydrophobicity.Biologically relevant enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines can be detected in the ALF of

Stieltjes electrostatic model interpretation for bound state problems

Indian Academy of Sciences (India)

In this paper, it is shown that Stieltjes electrostatic model and quantum Hamilton Jacobi formalism are analogous to each other. This analogy allows the bound state problem to mimic as unit moving imaginary charges i ℏ , which are placed in between the two fixed imaginary charges arising due to the classical turning ...

Relativistic bound states: a mass formula for vector mesons

International Nuclear Information System (INIS)

Richard, J.L.; Sorba, P.

1975-07-01

In the framework of a relativistic description of two particles bound states, a mass formula for vector mesons considered as quark-antiquark systems bound by harmonic oscillator like forces is proposed. Results in good agreement with experimental values are obtained [fr

Influence of apolipoprotein A-V on the metabolic fate of triacylglycerol.

Science.gov (United States)

Sharma, Vineeta; Forte, Trudy M; Ryan, Robert O

2013-04-01

Apolipoprotein (apo) A-V functions to modulate intracellular and extracellular triacylglycerol metabolism. The present review addresses molecular mechanisms underlying these effects. The relevance of apoA-V to human disease conditions is illustrated by the strong correlation between single nucleotide polymorphisms in APOA5, elevated plasma triacylglycerol and dyslipidemic disease. Despite undergoing processing for secretion from hepatocytes, a portion of apoA-V escapes this destiny and accumulates as a component of cytosolic lipid droplets. Expression of recombinant apoA-V in hepatocarcinoma cells results in increased lipid droplet size and number at the expense of triacylglycerol secretion.ApoA-V modulates atherosclerosis in hypercholesterolemic apoE null mice. ApoE null/human apoA-V transgenic mice had reduced levels of triacylglycerol and cholesterol in plasma along with decreased aortic lesion size. ApoA-V modulates triacylglycerol metabolic fate. Following its synthesis, apoA-V enters the endoplasmic reticulum and associates with membrane defects created by triacylglycerol accumulation. Association of apoA-V with endoplasmic reticulum membrane defects promotes nascent lipid droplets budding toward the cytosol. Despite its low concentration in plasma (∼150 ng/ml), apoA-V modulates lipoprotein metabolism by binding to glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. This interaction effectively localizes triacylglycerol-rich lipoproteins in the vicinity of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein1's other ligand, lipoprotein lipase.

Non-cooperative immobilization of residual water bound in lyophilized photosynthetic lamellae.

Science.gov (United States)

Harańczyk, Hubert; Baran, Ewelina; Nowak, Piotr; Florek-Wojciechowska, Małgorzata; Leja, Anna; Zalitacz, Dorota; Strzałka, Kazimierz

2015-12-01

This study applied 1H-NMR in time and in frequency domain measurements to monitor the changes that occur in bound water dynamics at decreased temperature and with increased hydration level in lyophilizates of native wheat photosynthetic lamellae and in photosynthetic lamellae reconstituted from lyophilizate. Proton relaxometry (measured as free induction decay = FID) distinguishes a Gaussian component S within the NMR signal (o). This comes from protons of the solid matrix of the lamellae and consists of (i) an exponentially decaying contribution L1 from mobile membrane protons, presumably from lipids, and from water that is tightly bound to the membrane surface and thus restricted in mobility; and (ii) an exponentially decaying component L2 from more mobile, loosely bound water pool. Both proton relaxometry data and proton spectroscopy show that dry lyophilizate incubated in dry air, i.e., at a relative humidity (p/p0) of 0% reveals a relatively high hydration level. The observed liquid signal most likely originates from mobile membrane protons and a tightly bound water fraction that is sealed in pores of dry lyophilizate and thus restricted in mobility. The estimations suggest that the amount of sealed water does not exceed the value characteristic for the main hydration shell of a phospholipid. Proton spectra collected for dry lyophilizate of photosynthetic lamellae show a continuous decrease in the liquid signal component without a distinct freezing transition when it is cooled down to -60ºC, which is significantly lower than the homogeneous ice nucleation temperature [Bronshteyn, V.L. et al. Biophys. J. 65 (1993) 1853].

Probing Andreev bound states in one-atom superconducting contacts

Energy Technology Data Exchange (ETDEWEB)

Pothier, Hugues; Janvier, Camille; Tosi, Leandro; Girit, Caglar; Goffman, Marcelo; Esteve, Daniel; Urbina, Cristian [Quantronics Group, SPEC, CEA-Saclay (France)

2015-07-01

Superconductors are characterized by a dissipationless current. Since the work of Josephson 50 years ago, it is known that a supercurrent can even flow through tunnel junctions between superconductors. This Josephson effect also occurs through any type of ''weak links'' between superconductors: non-superconducting materials, constrictions,.. A unified understanding of the Josephson effect has emerged from a mesoscopic description of weak links. It relies on the existence of doublets of localized states that have energies below the superconducting gap: the Andreev bound states. I will present experiments performed on the simplest conductor possible, a single-atom contact between superconductors, that illustrate these concepts. The most recent work demonstrates time-domain manipulation of quantum superpositions of Andreev bound states.

Self-bound droplets of a dilute magnetic quantum liquid

Science.gov (United States)

Schmitt, Matthias; Wenzel, Matthias; Böttcher, Fabian; Ferrier-Barbut, Igor; Pfau, Tilman

2016-11-01

Self-bound many-body systems are formed through a balance of attractive and repulsive forces and occur in many physical scenarios. Liquid droplets are an example of a self-bound system, formed by a balance of the mutual attractive and repulsive forces that derive from different components of the inter-particle potential. It has been suggested that self-bound ensembles of ultracold atoms should exist for atom number densities that are 108 times lower than in a helium droplet, which is formed from a dense quantum liquid. However, such ensembles have been elusive up to now because they require forces other than the usual zero-range contact interaction, which is either attractive or repulsive but never both. On the basis of the recent finding that an unstable bosonic dipolar gas can be stabilized by a repulsive many-body term, it was predicted that three-dimensional self-bound quantum droplets of magnetic atoms should exist. Here we report the observation of such droplets in a trap-free levitation field. We find that this dilute magnetic quantum liquid requires a minimum, critical number of atoms, below which the liquid evaporates into an expanding gas as a result of the quantum pressure of the individual constituents. Consequently, around this critical atom number we observe an interaction-driven phase transition between a gas and a self-bound liquid in the quantum degenerate regime with ultracold atoms. These droplets are the dilute counterpart of strongly correlated self-bound systems such as atomic nuclei and helium droplets.

Spectroscopic constants and potential energy curve of the iodine weakly bound 1u state correlating with the I(2P1/2) + I(2P1/2) dissociation limit

International Nuclear Information System (INIS)

Akopyan, M E; Baturo, V V; Lukashov, S S; Poretsky, S A; Pravilov, A M

2015-01-01

The stepwise three-step three-color laser population of the I 2 (β1 g , ν β , J β ) rovibronic states via the B0 u + , ν B , J B rovibronic states and rovibronic levels of the 1 u (bb) and 0 g + (bb) states mixed by hyperfine interaction is used for determination of rovibronic level energies of the weakly bound I 2 (1 u (bb)) state. Dunham coefficients of the state, Y i0 (i = 0–3), Y i1 (i = 0–2), Y 02 and Y 12 for the v 1 u  = 1–5, 8, 10, 15 and J 1 u  ≈ 9–87 ranges, the dissociation energy of the state, D e , and equilibrium I–I distance, R e , as well as the potential energy curve are determined. There are aperiodicities in the excitation spectrum corresponding to the β, ν β  = 23, J β  ← 1 u (bb), ν 1u  = 4, 5, J 1u progressions in the I 2  + Rg = He, Ar mixture, namely, a great number of lines which do not coincide with the R or P line progressions. Their positions conflict with the ΔJ-even selection rule. Furthermore, they do not correspond to the ΔJ-odd progression. (paper)

Bounds on heat transport in rapidly rotating Rayleigh–Bénard convection

International Nuclear Information System (INIS)

Grooms, Ian; Whitehead, Jared P

2015-01-01

The heat transport in rotating Rayleigh–Bénard convection is considered in the limit of rapid rotation (small Ekman number E) and strong thermal forcing (large Rayleigh number Ra). The analysis proceeds from a set of asymptotically reduced equations appropriate for rotationally constrained dynamics; the conjectured range of validity for these equations is Ra ≲ E −8/5 . A rigorous bound on heat transport of Nu ⩽ 20.56Ra 3 E 4 is derived in the limit of infinite Prandtl number using the background method. We demonstrate that the exponent in this bound cannot be improved on using a piece-wise monotonic background temperature profile like the one used here. This is true for finite Prandtl numbers as well, i.e. Nu ≲ Ra 3 is the best upper bound for this particular setup of the background method. The feature that obstructs the availability of a better bound in this case is the appearance of small-scale thermal plumes emanating from (or entering) the thermal boundary layer. The derived upper bound is consistent with, although significantly higher than the observed behaviour in simulations of the reduced equations, which find at most Nu ∼ Ra 2 E 8/3 . (paper)

Proton-bound cluster ions in ion mobility spectrometry

Science.gov (United States)

Ewing, R. G.; Eiceman, G. A.; Stone, J. A.

1999-01-01

Gaseous oxygen and nitrogen bases, both singly and as binary mixtures, have been introduced into ion mobility spectrometers to study the appearance of protonated molecules, and proton-bound dimers and trimers. At ambient temperature it was possible to simultaneously observe, following the introduction of molecule A, comparable intensities of peaks ascribable to the reactant ion (H2O)nH+, the protonated molecule AH+ and AH+ H2O, and the symmetrical proton bound dimer A2H+. Mass spectral identification confirmed the identifications and also showed that the majority of the protonated molecules were hydrated and that the proton-bound dimers were hydrated to a much lesser extent. No significant peaks ascribable to proton-bound trimers were obtained no matter how high the sample concentration. Binary mixtures containing molecules A and B, in some cases gave not only the peaks unique to the individual compounds but also peaks due to asymmetrical proton bound dimers AHB+. Such ions were always present in the spectra of mixtures of oxygen bases but were not observed for several mixtures of oxygen and nitrogen bases. The dimers, which were not observable, notable for their low hydrogen bond strengths, must have decomposed in their passage from the ion source to the detector, i.e. in a time less than approximately 5 ms. When the temperature was lowered to -20 degrees C, trimers, both homogeneous and mixed, were observed with mixtures of alcohols. The importance of hydrogen bond energy, and hence operating temperature, in determining the degree of solvation of the ions that will be observed in an ion mobility spectrometer is stressed. The possibility is discussed that a displacement reaction involving ambient water plays a role in the dissociation.

Apolipoprotein A-1 (apoA-1) deposition in, and release from, the enterocyte brush border: a possible role in transintestinal cholesterol efflux (TICE)?

Science.gov (United States)

Danielsen, E Michael; Hansen, Gert H; Rasmussen, Karina; Niels-Christiansen, Lise-Lotte; Frenzel, Franz

2012-03-01

Transintestinal cholesterol efflux (TICE) has been proposed to represent a non-hepatobiliary route of cholesterol secretion directly "from blood to gut" and to play a physiologically significant role in excretion of neutral sterols, but so far little is known about the proteins involved in the process. We have previously observed that apolipoprotein A-1 (apoA-1) synthesized by enterocytes of the small intestine is mainly secreted apically into the gut lumen during fasting where its assembly into chylomicrons and basolateral discharge is at a minimal level. In the present work we showed, both by immunomicroscopy and subcellular fractionation, that a fraction of the apically secreted apoA-1 in porcine small intestine was not released from the cell surface but instead deposited in the brush border. Cholesterol was detected in immunoisolated microvillar apoA-1, and it was partially associated with detergent resistant membranes (DRMs), indicative of localization in lipid raft microdomains. The apolipoprotein was not readily released from microvillar vesicles by high salt or by incubation with phosphatidylcholine-specific phospholipase C or trypsin, indicating a relatively firm attachment to the membrane bilayer. However, whole bile or taurocholate efficiently released apoA-1 at low concentrations that did not solubilize the transmembrane microvillar protein aminopeptidase N. Based on these findings and the well known role played by apoA-1 in extrahepatic cellular cholesterol removal and reverse cholesterol transport (RCT), we propose that brush border-deposited apoA-1 in the small intestine acts in TICE by mediating cholesterol efflux into the gut lumen. Copyright © 2011 Elsevier B.V. All rights reserved.

Maximum and minimum entropy states yielding local continuity bounds

Science.gov (United States)

Hanson, Eric P.; Datta, Nilanjana

2018-04-01

Given an arbitrary quantum state (σ), we obtain an explicit construction of a state ρɛ * ( σ ) [respectively, ρ * , ɛ ( σ ) ] which has the maximum (respectively, minimum) entropy among all states which lie in a specified neighborhood (ɛ-ball) of σ. Computing the entropy of these states leads to a local strengthening of the continuity bound of the von Neumann entropy, i.e., the Audenaert-Fannes inequality. Our bound is local in the sense that it depends on the spectrum of σ. The states ρɛ * ( σ ) and ρ * , ɛ (σ) depend only on the geometry of the ɛ-ball and are in fact optimizers for a larger class of entropies. These include the Rényi entropy and the minimum- and maximum-entropies, providing explicit formulas for certain smoothed quantities. This allows us to obtain local continuity bounds for these quantities as well. In obtaining this bound, we first derive a more general result which may be of independent interest, namely, a necessary and sufficient condition under which a state maximizes a concave and Gâteaux-differentiable function in an ɛ-ball around a given state σ. Examples of such a function include the von Neumann entropy and the conditional entropy of bipartite states. Our proofs employ tools from the theory of convex optimization under non-differentiable constraints, in particular Fermat's rule, and majorization theory.

Bounding the HL-index of a graph: a majorization approach.

Science.gov (United States)

Clemente, Gian Paolo; Cornaro, Alessandra

2016-01-01

In mathematical chemistry, the median eigenvalues of the adjacency matrix of a molecular graph are strictly related to orbital energies and molecular orbitals. In this regard, the difference between the occupied orbital of highest energy (HOMO) and the unoccupied orbital of lowest energy (LUMO) has been investigated (see Fowler and Pisansky in Acta Chim. Slov. 57:513-517, 2010). Motivated by the HOMO-LUMO separation problem, Jaklič et al. in (Ars Math. Contemp. 5:99-115, 2012) proposed the notion of HL -index that measures how large in absolute value are the median eigenvalues of the adjacency matrix. Several bounds for this index have been provided in the literature. The aim of the paper is to derive alternative inequalities to bound the HL -index. By applying majorization techniques and making use of some known relations, we derive new and sharper upper bounds for this index. Analytical and numerical results show the performance of these bounds on different classes of graphs.

Apolipoprotein E e4 allele does not increase the risk of early postoperative delirium after major surgery.

Science.gov (United States)

Abelha, Fernando José; Fernandes, Vera; Botelho, Miguela; Santos, Patricia; Santos, Alice; Machado, J C; Barros, Henrique

2012-02-01

BACKGROUND: A relationship between patients with a genetic predisposition to and those who develop postoperative delirium has not been yet determined. The aim of this study was to determine whether there is an association between apolipoprotein E epsilon 4 allele (APOE4) and delirium after major surgery. METHODS: Of 230 intensive care patients admitted to the post anesthesia care unit (PACU) over a period of 3 months, 173 were enrolled in the study. Patients' demographics and intra- and postoperative data were collected. Patients were followed for the development of delirium using the Intensive Care Delirium Screening Checklist, and DNA was obtained at PACU admission to determine apolipoprotein E genotype. RESULTS: Fifteen percent of patients developed delirium after surgery. Twenty-four patients had one copy of APOE4. The presence of APOE4 was not associated with an increased risk of early postoperative delirium (4% vs. 17%; P = 0.088). The presence of APOE4 was not associated with differences in any studied variables. Multivariate analysis identified age [odds ratio (OR) 9.3, 95% confidence interval (CI) 2.0-43.0, P = 0.004 for age ≥65 years), congestive heart disease (OR 6.2, 95% CI 2.0-19.3, P = 0.002), and emergency surgery (OR 59.7, 95% CI 6.7-530.5, P < 0.001) as independent predictors for development of delirium. The Simplified Acute Physiology Score II (SAPS II) and The Acute Physiology and Chronic Health Evaluation II (APACHE II) were significantly higher in patients with delirium (P < 0.001 and 0.008, respectively). Hospital mortality rates of these patients was higher and they had a longer median PACU stay. CONCLUSIONS: Apolipoprotein e4 carrier status was not associated with an increased risk for early postoperative delirium. Age, congestive heart failure, and emergency surgery were independent risk factors for the development of delirium after major surgery.

Evidence for a role of regulatory T cells in mediating the atheroprotective effect of apolipoprotein B peptide vaccine.

Science.gov (United States)

Wigren, M; Kolbus, D; Dunér, P; Ljungcrantz, I; Söderberg, I; Björkbacka, H; Fredrikson, G N; Nilsson, J

2011-05-01

Autoimmune responses against oxidized low-density lipoprotein are considered to play an important pro-inflammatory role in atherosclerosis and to promote disease progression. T-regulatory cells (Tregs) are immunosuppressive cells that have an important part in maintaining self-tolerance and protection against autoimmunity. We investigated whether aBp210, a prototype atherosclerosis vaccine based on a peptide sequence derived from apolipoprotein B, inhibits atherosclerosis through the activation of Tregs. Six-week-old Apoe(-/-) mice were immunized with aBp210 and received booster immunizations 3 and 5 weeks later, as well as 1 week before being killed at 25 weeks of age. At 12 weeks, immunized mice had increased expression of the Treg marker CD25 on circulating CD4 cells, and concanavalin A (Con A)-induced interferon-γ, interleukin (IL)-4, and IL-10 release from splenocytes was markedly depressed. At 25 weeks, there was a fivefold expansion of splenic CD4+ CD25+ Foxp3 Tregs, a 65% decrease in Con A-induced splenic T-cell proliferation and a 37% reduction in the development of atherosclerosis in immunized mice. Administration of blocking antibodies against CD25 neutralized aBp210-induced Treg activation as well as the reduction of atherosclerosis. The present findings demonstrate that immunization of Apoe(-/-) mice with the apolipoprotein B peptide vaccine aBp210 is associated with activation of Tregs. Administration of antibodies against CD25 results in depletion of Tregs and blocking of the atheroprotective effect of the vaccine. Modulation in atherosclerosis-related autoimmunity by antigen-specific activation of Tregs represents a novel approach for treatment of atherosclerosis. © 2010 The Association for the Publication of the Journal of Internal Medicine.

Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion.

Science.gov (United States)

Dresselhaus, Erica; Duerr, James M; Vincent, Fabien; Sylvain, Emily K; Beyna, Mercedes; Lanyon, Lorraine F; LaChapelle, Erik; Pettersson, Martin; Bales, Kelly R; Ramaswamy, Gayathri

2018-01-01

Despite the important role of apolipoprotein E (apoE) secretion from astrocytes in brain lipid metabolism and the strong association of apoE4, one of the human apoE isoforms, with sporadic and late onset forms of Alzheimer's disease (AD) little is known about the regulation of astrocytic apoE. Utilizing annotated chemical libraries and a phenotypic screening strategy that measured apoE secretion from a human astrocytoma cell line, inhibition of pan class I histone deacetylases (HDACs) was identified as a mechanism to increase apoE secretion. Knocking down select HDAC family members alone or in combination revealed that inhibition of the class I HDAC family was responsible for enhancing apoE secretion. Knocking down LXRα and LXRβ genes revealed that the increase in astrocytic apoE in response to HDAC inhibition occurred via an LXR-independent pathway. Collectively, these data suggest that pan class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion.

Effect of Mediterranean diet with and without weight loss on apolipoprotein B100 metabolism in men with metabolic syndrome

Science.gov (United States)

The objective of this study was to assess the effect of a Mediterranean diet (MedDiet) with and without weight loss (WL) on apolipoprotein B100 (apoB100) metabolism in men with metabolic syndrome. The diet of 19 men with metabolic syndrome (age, 24–62 years) was first standardized to a North America...

A cross-linking study on the particle species of human plasma high density lipoproteins.

Science.gov (United States)

Yachida, Y; Minari, O

1983-08-01

The present investigation was on the particle species of human plasma high density lipoprotein (HDL) characterized by the stoichiometry of their apoprotein components. HDL2-1, HDL2-2, HDL3-1, and HDL3-2 isolated from normal human plasma by sequential ultracentrifugal flotation were further subfractionated by Bio Gel A-5m gel chromatography or hydroxyapatite column chromatography, and three distinct subfractions were obtained. Subfraction 1 was obtained from all the HDL fractions and it contained mostly apolipoprotein A-I (A-I). Subfraction 2 was obtained from HDL2-2 and HDL3-1 and it contained A-I and apolipoprotein A-II (A-II) in the molar ratio of one to one, and subfraction 3 from HDL2-2 and HDL3-1 contained A-I and apolipoprotein C (C). Each subfraction was treated with bifunctional cross-linking reagents, and the intraparticle cross-linked products of apolipoproteins were examined by SDS-polyacrylamide gel electrophoresis. The results of the cross-linking studies indicated that the HDL2 fraction consisted mainly of lipoprotein particles of the (A-I)4 type and a few of the (A-I)5, (A-I)2(A-II)2, and (A-I)4(C)2 types, and that the HDL3 fraction consisted mainly of (A-I)2(A-II)2 type particles and a few (A-I)4, (A-I)3, (A-I)2, (A-I), and (A-I)3(C)2 type particles. From the results of analyses of the lipid components in the HDL of each type, it was suggested that the function of the particle species of the (A-I)n type (n = 1--5), which contained more cholesteryl ester than the (A-I)2(A-II)2 type, was concerned mainly with cholesterol metabolism.

Time-dependent association between platelet-bound fibrinogen and the Triton X-100 insoluble cytoskeleton

International Nuclear Information System (INIS)

Peerschke, E.I.

1991-01-01

Previous studies indicated a correlation between the formation of EDTA-resistant (irreversible) platelet-fibrinogen interactions and platelet cytoskeleton formation. The present study explored the direct association of membrane-bound fibrinogen with the Triton X-100 insoluble cytoskeleton of aspirin-treated, gel-filtered platelets, activated but not aggregated with 20 mumol/L adenosine diphosphate (ADP) or 150 mU/mL human thrombin (THR) when bound fibrinogen had become resistant to dissociation by EDTA. Conversion of exogenous 125I-fibrinogen to fibrin was prevented by adding Gly-Pro-Arg and neutralizing THR with hirudin before initiating binding studies. After 60 minutes at 22 degrees C, the cytoskeleton of ADP-treated platelets contained 20% +/- 12% (mean +/- SD, n = 14) of membrane-bound 125I-fibrinogen, representing 10% to 50% of EDTA-resistant fibrinogen binding. The THR-activated cytoskeleton contained 45% +/- 15% of platelet bound fibrinogen, comprising 80% to 100% of EDTA-resistant fibrinogen binding. 125I-fibrinogen was not recovered with platelet cytoskeletons if binding was inhibited by the RGDS peptide, excess unlabeled fibrinogen, or disruption of the glycoprotein (GP) IIb-IIIa complex by EDTA-treatment. Both development of EDTA-resistant fibrinogen binding and fibrinogen association with the cytoskeleton were time dependent and reached maxima 45 to 60 minutes after fibrinogen binding to stimulated platelets. Although a larger cytoskeleton formed after platelet stimulation with thrombin as compared with ADP, no change in cytoskeleton composition was noted with development of EDTA-resistant fibrinogen binding

Bound and rebound states

International Nuclear Information System (INIS)

Orzalesi, C.A.

1979-01-01

In relativistic quantum theory, bound states generate forces in the crossed channel; such forces can affect the binding and self-consistent solutions should be sought for the bound-state problem. The author investigates how self-consistency can be achieved by successive approximations, in a simple scalar model and with successive relativistic eikonal approximations (EAs). Within the generalized ladder approximation, some exact properties of the resulting ''first generation'' bound states are discussed. The binding energies in this approximation are rather small even for rather large values of the primary coupling constant. The coupling of the constituent particles to the first-generation reggeon is determined by a suitable EA and a new generalized ladder amplitude is constructed with rungs given either by the primary gluons or by the first-generation reggeons. The resulting new (second-generation) bound states are found in a reggeized EA. The size of the corrections to the binding energies due to the rebinding effects is surprisingly large. The procedure is then iterated, so as to find - again in an EA - the third-generation bound states. The procedure is found to be self-consistent already at this stage: the third-generation bound states coincide with those of second generation, and no further rebinding takes place in the higher iterations of the approximation method. Features - good and bad - of the model are discussed, as well as the possible relevance of rebinding mechanisms in hadron dynamics. (author)

Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice

NARCIS (Netherlands)

Vlijmen, B.J.M. van; Mensink, R.P.; Hof, H.B. van 't; Offermans, R.F.G.; Hofker, M.H.; Havekes, L.M.

1998-01-01

Studying the effects of dietary fish oil on VLDL metabolism in humans is subject to both large intra- and interindividual variability. In the present study we therefore used hyperlipidentic apolipoprotein (APO) E*3-Leiden mice, which have impaired chylomicron and very low density lipoprotein (VDL)

Replication of association of the apolipoprotein A1-C3-A4 gene cluster with the risk of gout.

Science.gov (United States)

Rasheed, Humaira; Phipps-Green, Amanda J; Topless, Ruth; Smith, Malcolm D; Hill, Catherine; Lester, Susan; Rischmueller, Maureen; Janssen, Matthijs; Jansen, Timothy L; Joosten, Leo A; Radstake, Timothy R; Riches, Philip L; Tausche, Anne-Kathrin; Lioté, Frederic; So, Alexander; van Rij, Andre; Jones, Gregory T; McCormick, Sally P; Harrison, Andrew A; Stamp, Lisa K; Dalbeth, Nicola; Merriman, Tony R

2016-08-01

Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout. We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Māori and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C). In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR = 1.53, P = 4.9 × 10(-6)) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR = 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR = 1.11, P = 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P ⩾ 0.10). Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Levels of apolipoprotein M are not associated with the risk of coronary heart disease in two independent case-control studies

DEFF Research Database (Denmark)

Ahnstrom, J.; Axler, O.; Jauhiainen, M.

2008-01-01

Apolipoprotein M (apoM), a 25 kDa plasma protein belonging to the lipocalin protein family, is predominantly associated with HDL. Studies in mice have suggested apoM to be important for the formation of pre-beta-HDL and to increase cholesterol efflux from macrophage foam cells. Overexpression...

Multipartite secret key distillation and bound entanglement

International Nuclear Information System (INIS)

Augusiak, Remigiusz; Horodecki, Pawel

2009-01-01

Recently it has been shown that quantum cryptography beyond pure entanglement distillation is possible and a paradigm for the associated protocols has been established. Here we systematically generalize the whole paradigm to the multipartite scenario. We provide constructions of new classes of multipartite bound entangled states, i.e., those with underlying twisted Greenberger-Horne-Zeilinger (GHZ) structure and nonzero distillable cryptographic key. We quantitatively estimate the key from below with the help of the privacy squeezing technique.

Bionic Control of Cheetah Bounding with a Segmented Spine.

Science.gov (United States)

Wang, Chunlei; Wang, Shigang

2016-01-01

A cheetah model is built to mimic real cheetah and its mechanical and dimensional parameters are derived from the real cheetah. In particular, two joints in spine and four joints in a leg are used to realize the motion of segmented spine and segmented legs which are the key properties of the cheetah bounding. For actuating and stabilizing the bounding gait of cheetah, we present a bioinspired controller based on the state-machine. The controller mainly mimics the function of the cerebellum to plan the locomotion and keep the body balance. The haptic sensor and proprioception system are used to detect the trigger of the phase transition. Besides, the vestibular modulation could perceive the pitching angle of the trunk. At last, the cerebellum acts as the CPU to operate the information from the biological sensors. In addition, the calculated results are transmitted to the low-level controller to actuate and stabilize the cheetah bounding. Moreover, the delay feedback control method is employed to plan the motion of the leg joints to stabilize the pitching motion of trunk with the stability criterion. Finally, the cyclic cheetah bounding with biological properties is realized. Meanwhile, the stability and dynamic properties of the cheetah bounding gait are analyzed elaborately.

Bionic Control of Cheetah Bounding with a Segmented Spine

Directory of Open Access Journals (Sweden)

Chunlei Wang

2016-01-01

Full Text Available A cheetah model is built to mimic real cheetah and its mechanical and dimensional parameters are derived from the real cheetah. In particular, two joints in spine and four joints in a leg are used to realize the motion of segmented spine and segmented legs which are the key properties of the cheetah bounding. For actuating and stabilizing the bounding gait of cheetah, we present a bioinspired controller based on the state-machine. The controller mainly mimics the function of the cerebellum to plan the locomotion and keep the body balance. The haptic sensor and proprioception system are used to detect the trigger of the phase transition. Besides, the vestibular modulation could perceive the pitching angle of the trunk. At last, the cerebellum acts as the CPU to operate the information from the biological sensors. In addition, the calculated results are transmitted to the low-level controller to actuate and stabilize the cheetah bounding. Moreover, the delay feedback control method is employed to plan the motion of the leg joints to stabilize the pitching motion of trunk with the stability criterion. Finally, the cyclic cheetah bounding with biological properties is realized. Meanwhile, the stability and dynamic properties of the cheetah bounding gait are analyzed elaborately.

Lifestyle and Dietary Determinants of Serum Apolipoprotein A1 and Apolipoprotein B Concentrations: Cross-Sectional Analyses within a Swedish Cohort of 24,984 Individuals

Directory of Open Access Journals (Sweden)

Kasper Frondelius

2017-02-01

Full Text Available Low serum apolipoprotein (Apo A1 concentrations and high serum ApoB concentrations may be better markers of the risk of cardiovascular disease than high-density lipoprotein (HDL and low-density lipoprotein (LDL. However, the associations between modifiable lifestyle factors and Apo concentrations have not been investigated in detail. Therefore, this study investigated the associations between Apo concentrations and education, lifestyle factors and dietary intake (macronutrients and 34 food groups. These cross-sectional associations were examined among 24,984 individuals in a Swedish population-based cohort. Baseline examinations of the cohort were conducted between 1991 and 1996. Dietary intake was assessed using a modified diet history method. The main determinants of high ApoA1 concentrations (r between 0.05 and 0.25 were high alcohol consumption, high physical activity, non-smoking, and a low body mass index (BMI, and the main determinants of high ApoB concentrations were smoking and a high BMI. The intake of sucrose and food products containing added sugar (such as pastries, sweets, chocolate, jam/sugar and sugar-sweetened beverages was negatively correlated with ApoA1 concentrations and positively correlated with ApoB concentrations and the ApoB/ApoA1 ratio, whereas the intake of fermented dairy products, such as fermented milk and cheese, was positively correlated with ApoA1 concentrations and negatively correlated with the ApoB/ApoA1 ratio. These results indicate that smoking, obesity, low physical activity, low alcohol consumption and a diet high in sugar and low in fermented dairy products are correlated with an unfavorable Apo profile.

A cluster expansion for bound three-alpha particles as a three-body problem

International Nuclear Information System (INIS)

Osman, A.

1981-08-01

A three-body model is proposed to study the nuclear bound states. The nucleus is described as a bound state of three clusters. A cluster expansion is introduced for the three cluster bound state problem. The present integral equations are treated by simple approximate solutions, which lead to effective potentials by using the present cluster expansion. The 12 C nucleus is described as a three-alpha particle bound state. The binding energy of 12 C is calculated numerically using the present cluster expansion as bound three-alpha clusters. The present three-body cluster expansion calculations are very near to the exact three-body calculations using separable potentials. The present theoretical calculations are in good agreement with the experimental measurements. (author)

Bounds for Asian basket options

Science.gov (United States)

Deelstra, Griselda; Diallo, Ibrahima; Vanmaele, Michèle

2008-09-01

In this paper we propose pricing bounds for European-style discrete arithmetic Asian basket options in a Black and Scholes framework. We start from methods used for basket options and Asian options. First, we use the general approach for deriving upper and lower bounds for stop-loss premia of sums of non-independent random variables as in Kaas et al. [Upper and lower bounds for sums of random variables, Insurance Math. Econom. 27 (2000) 151-168] or Dhaene et al. [The concept of comonotonicity in actuarial science and finance: theory, Insurance Math. Econom. 31(1) (2002) 3-33]. We generalize the methods in Deelstra et al. [Pricing of arithmetic basket options by conditioning, Insurance Math. Econom. 34 (2004) 55-57] and Vanmaele et al. [Bounds for the price of discrete sampled arithmetic Asian options, J. Comput. Appl. Math. 185(1) (2006) 51-90]. Afterwards we show how to derive an analytical closed-form expression for a lower bound in the non-comonotonic case. Finally, we derive upper bounds for Asian basket options by applying techniques as in Thompson [Fast narrow bounds on the value of Asian options, Working Paper, University of Cambridge, 1999] and Lord [Partially exact and bounded approximations for arithmetic Asian options, J. Comput. Finance 10 (2) (2006) 1-52]. Numerical results are included and on the basis of our numerical tests, we explain which method we recommend depending on moneyness and time-to-maturity.

Upper bounds on the number of errors corrected by a convolutional code

DEFF Research Database (Denmark)

Justesen, Jørn

2004-01-01

We derive upper bounds on the weights of error patterns that can be corrected by a convolutional code with given parameters, or equivalently we give bounds on the code rate for a given set of error patterns. The bounds parallel the Hamming bound for block codes by relating the number of error...

Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.