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Sample records for a-i dmpc small

  1. Structure and Conformational Dynamics of DMPC/Dicationic Surfactant and DMPC/Dicationic Surfactant/DNA Systems

    PubMed Central

    Pietralik, Zuzanna; Krzysztoń, Rafał; Kida, Wojciech; Andrzejewska, Weronika; Kozak, Maciej

    2013-01-01

    Amphiphilic dicationic surfactants, known as gemini surfactants, are currently studied for gene delivery purposes. The gemini surfactant molecule is composed of two hydrophilic “head” groups attached to hydrophobic chains and connected via molecular linker between them. The influence of different concentrations of 1,5-bis (1-imidazolilo-3- decyloxymethyl) pentane chloride (gemini surfactant) on the thermotropic phase behaviour of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers with and without the presence of DNA was investigated using Fourier transformed infrared (FTIR) and circular dichroism (CD) spectroscopies, small angle scattering of synchrotron radiation and differential scanning calorimetry. With increasing concentration of surfactant in DMPC/DNA systems, a disappearance of pretransition and a decrease in the main phase transition enthalpy and temperature were observed. The increasing intensity of diffraction peaks as a function of surfactant concentration also clearly shows the ability of the surfactant to promote the organisation of lipid bilayers in the multilayer lamellar phase. PMID:23571492

  2. Comprehensive examination of mesophases formed by DMPC and DHPC mixtures.

    PubMed

    Harroun, Thad A; Koslowsky, Martin; Nieh, Mu-Ping; de Lannoy, Charles-François; Raghunathan, V A; Katsaras, John

    2005-06-07

    Mixtures of long- and short-chain phospholipids, specifically 14:0 and 6:0 phosphatidylcholines (DMPC and DHPC), have been used successfully in NMR studies as magnetically alignable substrates for membrane-associated proteins. However, recent publications have shown that the phase behavior of these mixtures is much more complex than originally thought. Using polarized light microscopy and small-angle neutron scattering, phase diagrams of DMPC/DHPC mixtures at molar ratios of 2, 3.2, and 5 have been determined. Generally, at temperatures below the main-chain melting transition of DMPC (T(M) = 23 degrees C), an isotropic phase of disk-like micelles is found. At high temperatures (T > 50 degrees C), a lamellar phase consisting of either multilamellar vesicles (MLV) or extended lamellae is formed, which at low lipid concentrations (e.g., MLV) coexists with an excess of water. At intermediate temperatures and lipid concentrations, a chiral nematic phase made up of worm-like micelles was observed.

  3. Influence of phytosphingosine-type ceramides on the structure of DMPC membrane.

    PubMed

    Zbytovská, J; Kiselev, M A; Funari, S S; Garamus, V M; Wartewig, S; Neubert, R

    2005-12-01

    The present paper describes the influence of the ceramides with phytosphingosine base, N-stearoylphytosphingosine (Cer[NP]) and alpha-hydroxy-N-stearoylphytosphingosine (Cer[AP]), on the structure and properties of multilamellar (MLVs) and unilamellar vesicles (ULVs) of dimyristoylphosphatidylcholine (DMPC). The lamellar repeat distance, D, has been measured at various temperatures using small angle X-ray diffraction. The incorporation of ceramides into the DMPC membrane causes larger D compared to pure DMPC membrane. For both ceramide types, at 32 degrees C, there is a linear relationship between the D value and the ceramide concentration. However, there is no such dependence at 13 or 60 degrees C. Unlike Cer[AP], Cer[NP] induces a new phase with a repeat distance of 38.5A. The membrane thickness and the vesicle radius of ULVs in water and in sucrose solution were calculated from small angle neutron scattering curves. Phytosphingosine ceramides increase both the membrane thickness and the radius in comparison to pure DMPC ULVs. The stability of ULVs in time was studied by dynamic light scattering. Both ceramides induce an aggregation of the ULVs into micrometer sized non-multilamellar structures in pure water. Presence of sucrose in the environment averts the vesicle aggregation.

  4. Analysing DHPC/DMPC bicelles by diffusion NMR and multivariate decomposition.

    PubMed

    Björnerås, Johannes; Nilsson, Mathias; Mäler, Lena

    2015-11-01

    Mixtures of lipids and detergents are known to form bicelles at certain parameter ranges, but many uncertainties remain concerning the details of the phase behaviour of these mixtures and the morphology of the formed lipid assemblies. Here we used nuclear magnetic resonance (NMR) diffusion data in combination with the multivariate processing method speedy component resolution (SCORE) to analyse mixtures of 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) with the relative concentration q=[DMPC]/[DHPC]=0.5 at total lipid concentrations ranging from 15 to 300 mM. With this approach we were able to resolve the heavily overlapping mixture spectra into component spectra and obtained reliable diffusion coefficients for lipid concentrations in the range 15 to 300 mM, although at high concentrations (250-300 mM), non-negativity constraints or overfactoring was required to successfully decompose the data. At 50-300 mM total lipid concentration, the radii estimated from the diffusion coefficient of DMPC indicate assemblies of the appropriate bicelle size, although small size variations exist, while at lower concentrations the morphology appears to change to larger assemblies. Taken together, the results suggest that for q=0.5 DMPC/DHPC mixtures there is a relatively broad concentration range above 50 mM where bicelles may reliably be assumed to adopt the 'classical' bicelle morphology. The study clearly demonstrates the usefulness of our approach for accurately determining physical properties of complex mixtures such as bicelles. Both reliable diffusion coefficients and chemical shifts can be derived from overlapping data. This should prove useful for analysing the behaviour of other, more complex, lipid mixtures. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Morphology of magnetically aligning DMPC/DHPC aggregates-perforated sheets, not disks.

    PubMed

    van Dam, Lorens; Karlsson, Göran; Edwards, Katarina

    2006-03-28

    The morphology of DMPC/DHPC mixtures at total lipid concentration cL = 5% (w/w) and DMPC/DHPC ratio q approximately 3, doped with small amounts of DMPG or CTAB, was investigated. 31P NMR was used to identify the magnetically aligning phase, and cryo-transmission electron microscopy (cryo-TEM) was employed for structural characterization. Magnetic alignment was found to occur between approximately 30 and approximately 45 degrees C, and cryo-TEM showed that the magnetically aligning phase consisted of extended sheets with a lacelike structure. The aggregates are best described as intermediates between two-dimensional networks of flattened, highly branched, cylindrical micelles and lamellar sheets perforated by large irregular holes. DHPC most likely covers the edges of the holes, while DMPC makes up the bilayer bulk of the aggregates. However, 20-43% of the DHPC takes part in the bilayer, corresponding to 6-12% of the bilayer being made up of DHPC. This fraction increases with increasing temperature. At temperatures above 45 degrees C, the aligning phase collapses.

  6. Effect of tetracaine on DMPC and DMPC+cholesterol biomembrane models: liposomes and monolayers.

    PubMed

    Serro, A P; Galante, R; Kozica, A; Paradiso, P; da Silva, A M P S Gonçalves; Luzyanin, K V; Fernandes, A C; Saramago, B

    2014-04-01

    Different types of lipid bilayers/monolayers have been used to simulate the cellular membranes in the investigation of the interactions between drugs and cells. However, to our knowledge, very few studies focused on the influence of the chosen membrane model upon the obtained results. The main objective of this work is to understand how do the nature and immobilization state of the biomembrane models influence the action of the local anaesthetic tetracaine (TTC) upon the lipid membranes. The interaction of TTC with different biomembrane models of dimyristoylphosphatidylcholine (DMPC) with and without cholesterol (CHOL) was investigated through several techniques. A quartz crystal microbalance with dissipation (QCM-D) was used to study the effect on immobilized liposomes, while phosphorus nuclear magnetic resonance ((31)P-NMR) and differential scanning calorimetry (DSC) were applied to liposomes in suspension. The effect of TTC on Langmuir monolayers of lipids was also investigated through surface pressure-area measurements at the air-water interface. The general conclusion was that TTC has a fluidizing effect on the lipid membranes and, above certain concentrations, induces membrane swelling or even solubilization. However, different models led to variable responses to the TTC action. The intensity of the disordering effect caused by TTC increased in the following order: supported liposomes

  7. Morphological effects of ceramide on DMPC/DHPC bicelles.

    PubMed

    Barbosa-Barros, L; De la Maza, A; Walther, P; Estelrich, J; López, O

    2008-04-01

    Freeze fracture electron microscopy and dynamic light scattering were applied to characterize the morphological changes of DMPC/DHPC bicellar systems induced by the addition of ceramides. The results demonstrate a tendency of the DMPC/DHPC aggregates to evolve forming elongated or tubular structures with the increase of the temperature. At 20 degrees C, low concentrations of ceramide promote the appearance of elongated structures with twisted zones. Higher concentrations of this lipid lead to the formation of liposomes along the elongated structures. The increase of the temperature to 40 degrees C induces the growth of the structures containing low concentrations of ceramide forming branched aggregates. In samples with high amounts of ceramide, the increase of temperature causes phase separation and the formation of a mixed system composed by liposomes and multilamellar tubules. The morphological effects induced by ceramides in this new membrane model give new insights for the role played by this lipid in biological membranes.

  8. The effect of selected surfactants on the structure of a bicellar system (DMPC/DHPC) studied by SAXS

    NASA Astrophysics Data System (ADS)

    Kozak, Maciej; Domka, Ludwik; Jurga, Stefan

    2007-11-01

    The stabilizing or disturbing effect of different surfactants on the bicellar phase of phospholipids significantly depends on their type. The effect of different surfactants on the bicellar structure made of a mixture of phospholipids 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2-dihexanoyl-sn-glycero-3-phospho-choline (DMPC/DHPC) has been studied by the small angle scattering of synchrotron radiation. The study has been performed for three surfactants: dodecyldimethyl-(hexyloxymethyl)ammonium chloride, n-undecylammonium chloride and t-octylphenoxypolyethoxyethanol (Triton X-100) introduced into a bicellar solution of DMPC/DHPC (2.8:1). The bicellar phase has been disturbed in the shortest time in the presence of dodecyldimethyl-(hexyloxymethyl)ammonium chloride in this system a transition from the bicellar to lamellar structure has been directly visible. The changes have been less pronounced in the presence of undecylammonium chloride and practically not noted in the presence of Triton X-100.

  9. Simulated biophysical experimental techniques for chlorhexidine in dmpc/cholesterol systems

    NASA Astrophysics Data System (ADS)

    van Oosten, Brad; Harroun, Thad

    We have investigated the use of molecular dynamic simulations and the MARTINI force field to simulate isothermal titration calorimetry and differential scanning calorimetry techniques. The goal of these simulations was to observe how well they can reproduce the concentration effects of the addition of the small molecule chlorhexidine (CHX) into a model DMPC membrane containing varying concentrations of cholesterol. We constructed a coarse grained model for CHX compatible with the MARTINI force field. We were able to mimic an isothermal titration calorimetry experiment by repeatedly adding CHX into a DMPC membrane. With the increased concentration, we observed a decreasing affinity between CHX and the membrane as well as a resulting increase in the reaction time before the system was equilibrated. We then performed a controlled cooling of the membrane with various CHX concentrations to mimic a differential scanning calorimetry experiment. A change in membrane structure accompanied by a spike in the specific heat was measured at specific temperature Tm signaling a phase transition. We then varied the concentration of CHX as well as the addition of varying concentrations of cholesterol to observe trends in the change to Tm due to the addition of CHX and cholesterol.

  10. Structure and phase transitions of the multilamellar DMPC membranes in presence of the DMSO and DESO

    NASA Astrophysics Data System (ADS)

    Gorshkova, Yu E.; Ivankov, O. I.

    2017-05-01

    The structure and phase transitions of the prepared and formed spontaneously multilamellar vesicles (MLVs) of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) in dimethyl sulfoxide (DMSO) and diethyl sulfoxide (DESO) were investigated using small angle neutron scattering (SANS). The both polar aprotic solvents increase the temperature of the main phase transition (Tm ). The pre-transition does not observed at sulfoxides mole fraction X = 0.2. The transition of the MLVs DMPC in the presence DMSO from gel to liquid-crystalline phase occurs at lower temperature. The method of the MLVs preparation has directly effects on the temperature of the main phase transition and its structure. The value of Tm is higher with ∼ 4.6 ºC in case of the spontaneous forming MLVs from extruded ULVs. The thickness of the solvent layer for prepared MLVs is less by 4.0 Å in gel phase and by 5.6 Å in liquid-crystalline phase than the thickness of the solvent layer for spontaneously formed MLVs.

  11. Direct observation and characterization of DMPC/DHPC aggregates under conditions relevant for biological solution NMR.

    PubMed

    van Dam, Lorens; Karlsson, Göran; Edwards, Katarina

    2004-08-30

    We have used cryo-transmission electron microscopy (cryo-TEM) for inspection of aggregates formed by dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC) in aqueous solution at total phospholipid concentrations cL < or = 5% and DMPC/DHPC ratios q < or = 4.0. In combination with ocular inspections, we are able to sketch out this part of phase-diagram at T = 14-80 degrees C. The temperature and the ratio q are the dominating variables for changing sample morphology, while cL to a lesser extent affects the aggregate structure. At q = 0.5, small, possibly disc-shaped, aggregates with a diameter of approximately 6 nm are formed. At higher q-values, distorted discoidal micelles that tend to short cylindrical micelles are observed. The more well-shaped discs have a diameter of around 20 nm. Upon increasing q or the temperature, long slightly flattened cylindrical micelles that eventually branch are formed. A holey lamellar phase finally appears upon further elevation of q or temperature. The implications for biological NMR work are two. First, discs prepared as membrane mimics are frequently much smaller than predicted by current "ideal bicelle" models. Second, the q approximately 3 preparations used for aligning water-soluble biomolecules in magnetic fields consist of perforated lamellar sheets. Furthermore, the discovered sequence of morphological transitions may have important implications for the development of bicelle-based membrane protein crystallization methods.

  12. Component and state separation in DMPC/DSPC lipid bilayers: a Monte Carlo simulation study.

    PubMed Central

    Michonova-Alexova, Ekaterina I; Sugár, István P

    2002-01-01

    In this paper a two-state, two-component, Ising-type model is used to simulate the lateral distribution of the components and gel/fluid state acyl chains in dimyristoylphosphatidylcholine/distearoylphosphatidylcholine (DMPC/DSPC) lipid bilayers. The same model has been successful in calculating the excess heat capacity curves, the fluorescence recovery after photobleaching (FRAP) threshold temperatures, the most frequent center-to-center distances between DSPC clusters, and the fractal dimensions of gel clusters (Sugar, I. P., T. E. Thompson, and R. L. Biltonen, 1999. Biophys. J. 76:2099-2110). Depending on the temperature and mole fraction the population of the cluster size is either homogeneous or inhomogeneous. In the inhomogeneous population the size of the largest cluster scales with the size of the system, while the rest of the clusters remain small with increasing system size. In a homogeneous population, however, every cluster remains small with increasing system size. For both compositional and fluid/gel state clusters, threshold temperatures-the so-called percolation threshold temperatures-are determined where change in the type of the population takes place. At a given mole fraction, the number of percolation threshold temperatures can be 0, 1, 2, or 3. By plotting these percolation threshold temperatures on the temperature/mole fraction plane, the diagrams of component and state separation of DMPC/DSPC bilayers are constructed. In agreement with the small-angle neutron scattering measurements, the component separation diagram shows nonrandom lateral distribution of the components not only in the gel-fluid mixed phase region, but also in the pure gel and pure fluid regions. A combined diagram of component and state separation is constructed to characterize the lateral distribution of lipid components and gel/fluid state acyl chains in DMPC/DSPC mixtures. While theoretical phase diagrams of two component mixtures can be constructed only in the case of

  13. Unilamellar DMPC Vesicles in Aqueous Glycerol: Preferential Interactions and Thermochemistry

    PubMed Central

    Westh, Peter

    2003-01-01

    Glycerol is accumulated in response to environmental stresses in a diverse range of organisms. Understanding of favorable in vivo effects of this solute requires insight into its interactions with biological macromolecules, and one access to this information is the quantification of so-called preferential interactions in glycerol-biopolymer solutions. For model membrane systems, preferential interactions have been discussed, but not directly measured. Hence, we have applied a new differential vapor pressure equipment to quantify the isoosmotic preferential binding parameter, Γμ1, for systems of unilamellar vesicles of DMPC in aqueous glycerol. It is found that Γμ1 decreases linearly with the glycerol concentration with a slope of −0.14 ± 0.014 per molal. This implies that glycerol is preferentially excluded from the membrane-solvent interface. Calorimetric investigations of the same systems showed that the glycerol-DMPC interactions are weakly endothermic, and the temperature of the main phase transition increases slightly (0.16°C per molal) with the glycerol concentration. The results are discussed with respect to a molecular picture which takes into account both the partitioning of glycerol into the membrane and the preferential exclusion from the hydration layer, and it is concluded that the latter effect contributes about four times stronger than the former to the net interaction. PMID:12524287

  14. Unilamellar DMPC vesicles in aqueous glycerol: preferential interactions and thermochemistry.

    PubMed

    Westh, Peter

    2003-01-01

    Glycerol is accumulated in response to environmental stresses in a diverse range of organisms. Understanding of favorable in vivo effects of this solute requires insight into its interactions with biological macromolecules, and one access to this information is the quantification of so-called preferential interactions in glycerol-biopolymer solutions. For model membrane systems, preferential interactions have been discussed, but not directly measured. Hence, we have applied a new differential vapor pressure equipment to quantify the isoosmotic preferential binding parameter, Gamma( micro 1), for systems of unilamellar vesicles of DMPC in aqueous glycerol. It is found that Gamma( micro 1) decreases linearly with the glycerol concentration with a slope of -0.14 +/- 0.014 per molal. This implies that glycerol is preferentially excluded from the membrane-solvent interface. Calorimetric investigations of the same systems showed that the glycerol-DMPC interactions are weakly endothermic, and the temperature of the main phase transition increases slightly (0.16 degrees C per molal) with the glycerol concentration. The results are discussed with respect to a molecular picture which takes into account both the partitioning of glycerol into the membrane and the preferential exclusion from the hydration layer, and it is concluded that the latter effect contributes about four times stronger than the former to the net interaction.

  15. Thyroid hormone interactions with DMPC bilayers. A molecular dynamics study.

    PubMed

    Petruk, Ariel A; Marti, Marcelo A; Alvarez, Rosa María S

    2009-10-08

    The structure and dynamics of thyroxine (T4), distal and proximal conformers of 3',3,5-triiodo-l-thyronine (T3d and T3p), and 3,5-diiodo-l-thyronine (T2) upon interaction with DMPC membranes were analyzed by means of molecular dynamics simulations. The locations, the more stable orientations, and the structural changes adopted by the hormones in the lipid medium evidence that the progressive iodine substitution on the beta ring lowers both the possibility of penetration and the transversal mobility in the membrane. However, the results obtained for T3d show that the number of iodine atoms in the molecule is not the only relevant factor in the hormone behavior but also the orientation of the single iodine substitution. The electrostatic interactions between the zwitterion group of the hormones with specific groups in the hydrophilic region of the membrane as well as the organization of the alkyl chains around the aromatic beta ring of the hormone were evaluated in terms of several radial distribution functions.

  16. Cholesterol orientation and tilt modulus in DMPC bilayers

    PubMed Central

    Khelashvili, George; Pabst, Georg; Harries, Daniel

    2010-01-01

    We performed molecular dynamics (MD) simulations of hydrated bilayers containing mixtures of dimyristoylphosphatidylcholine (DMPC) and Cholesterol at various ratios, to study the effect of cholesterol concentration on its orientation, and to characterize the link between cholesterol tilt and overall phospholipid membrane organization. The simulations show a substantial probability for cholesterol molecules to transiently orient perpendicular to the bilayer normal, and suggest that cholesterol tilt may be an important factor for inducing membrane ordering. In particular, we find that as cholesterol concentration increases (1%–40% cholesterol) the average cholesterol orientation changes in a manner strongly (anti)correlated with the variation in membrane thickness. Furthermore, cholesterol orientation is found to be determined by the aligning force exerted by other cholesterol molecules. To quantify this aligning field, we analyzed cholesterol orientation using, to our knowledge, the first estimates of the cholesterol tilt modulus χ from MD simulations. Our calculations suggest that the aligning field that determines χ is indeed strongly linked to sterol composition. This empirical parameter (χ) should therefore become a useful quantitative measure to describe cholesterol interaction with other lipids in bilayers, particularly in various coarse-grained force fields. PMID:20518573

  17. Morphological Characterization of DMPC/CHAPSO Bicellar Mixtures: A Combined SANS and NMR Study

    SciTech Connect

    Li, Ming; Morales, Hannah H.; Katsaras, John; Kučerka, Norbert; Yang, Yongkun; Macdonald, Peter M.; Nieh, Mu-Ping

    2013-12-23

    Spontaneously forming structures of a system composed of dimyristoyl phosphatidylcholine (DMPC) and 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate (CHAPSO) were studied by small-angle neutron scattering (SANS), 31P NMR, and stimulated echo (STE) pulsed field gradient (PFG) 1H NMR diffusion measurements. Charged lipid dimyristoyl phosphatidylglycerol (DMPG) was used to induce different surface charge densities. The structures adopted were investigated as a function of temperature and lipid concentration for samples with a constant molar ratio of long-chain to short-chain lipids (=3). In the absence of DMPG, zwitterionic bicellar mixtures exhibited a phase transition from discoidal bicelles, or ribbons, to multilamellar vesicles either upon dilution or with increased temperature. CHAPSO-containing mixtures showed a higher thermal stability in morphology than DHPC-containing mixtures at the corresponding lipid concentrations. In the presence of DMPG, discoidal bicelles (or ribbons) were also found at low temperature and lower lipid concentration mixtures. At high temperature, perforated lamellae were observed in high concentration mixtures ( ≥ 7.5 wt %) whereas uniform unilamellar vesicles and bicelles formed in low-concentration mixtures ( ≤ 2.5 wt %), respectively, when the mixtures were moderately and highly charged. Lastly, from the results, spontaneous structural diagrams of the zwitterionic and charged systems were constructed.

  18. Thermotropic Behavior of Membranes Containing DMPC and Chemically and Stereochemically Pure Sphingomyelin upon Cholesterol Addition

    NASA Astrophysics Data System (ADS)

    Shibakami, Motonari; Sonoyama, Masashi; Goto, Rie; Mori, Michiko; Suzuki, Hikokazu; Mitaku, Shigeki

    2004-12-01

    High sensitivity differential scanning calorimetry is applied to the problem of interaction between phospholipids and cholesterol in bilayers, i.e., whether or not cholesterol shows a preferential interaction with sphingomyelins over glycerophospholipids. The simplest system yet used for exploring this problem is designed—one composed of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC), chemically and stereochemically pure N-palmitoyl-sphingomyelin (pure-C16:0-SM), and cholesterol, based on a belief that chemically and stereochemically purity excludes chain length mismatch and chiral interaction that may affect the interaction from this system. Incremental addition of cholesterol to mixtures of DMPC and pure-C16:0-SM with a ratio of 6:4 or 4:6 leads to a continuous shift in endotherm due to DMPC toward a lower temperature. Such results indicate that cholesterol favors pure-C16:0-SM.

  19. Strong Static Magnetic Fields Increase the Gel Signal in Partially Hydrated DPPC/DMPC Membranes.

    PubMed

    Tang, Jennifer; Alsop, Richard J; Schmalzl, Karin; Epand, Richard M; Rheinstädter, Maikel C

    2015-09-29

    NIt was recently reported that static magnetic fields increase lipid order in the hydrophobic membrane core of dehydrated native plant plasma membranes [Poinapen, Soft Matter 9:6804-6813, 2013]. As plasma membranes are multicomponent, highly complex structures, in order to elucidate the origin of this effect, we prepared model membranes consisting of a lipid species with low and high melting temperature. By controlling the temperature, bilayers coexisting of small gel and fluid domains were prepared as a basic model for the plasma membrane core. We studied molecular order in mixed lipid membranes made of dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) using neutron diffraction in the presence of strong static magnetic fields up to 3.5 T. The contribution of the hydrophobic membrane core was highlighted through deuterium labeling the lipid acyl chains. There was no observable effect on lipid organization in fluid or gel domains at high hydration of the membranes. However, lipid order was found to be enhanced at a reduced relative humidity of 43%: a magnetic field of 3.5 T led to an increase of the gel signal in the diffraction patterns of 5%. While all biological materials have weak diamagnetic properties, the corresponding energy is too small to compete against thermal disorder or viscous effects in the case of lipid molecules. We tentatively propose that the interaction between the fatty acid chains' electric moment and the external magnetic field is driving the lipid tails in the hydrophobic membrane core into a better ordered state.

  20. Free energy landscapes of sodium ions bound to DMPC-cholesterol membrane surfaces at infinite dilution.

    PubMed

    Yang, Jing; Bonomi, Massimiliano; Calero, Carles; Martí, Jordi

    2016-04-07

    Exploring the free energy landscapes of metal cations on phospholipid membrane surfaces is important for the understanding of chemical and biological processes in cellular environments. Using metadynamics simulations we have performed systematic free energy calculations of sodium cations bound to DMPC phospholipid membranes with cholesterol concentration varying between 0% (cholesterol-free) and 50% (cholesterol-rich) at infinite dilution. The resulting free energy landscapes reveal the competition between binding of sodium to water and to lipid head groups. Moreover, the binding competitiveness of lipid head groups is diminished by cholesterol contents. As cholesterol concentration increases, the ionic affinity to membranes decreases. When cholesterol concentration is greater than 30%, the ionic binding is significantly reduced, which coincides with the phase transition point of DMPC-cholesterol membranes from a liquid-disordered phase to a liquid-ordered phase. We have also evaluated the contributions of different lipid head groups to the binding free energy separately. The DMPC's carbonyl group is the most favorable binding site for sodium, followed by DMPC's phosphate group and then the hydroxyl group of cholesterol.

  1. Use of DMPC and DSPC lipids for verapamil and naproxen permeability studies by PAMPA.

    PubMed

    Alvarez-Figueroa, M J; Contreras-Garrido, B C; Soto-Arriaza, M A

    2015-04-01

    Verapamil and naproxen Parallel Artificial Membrane Permeability Assay (PAMPA) permeability was studied using lipids not yet reported for this model in order to facilitate the quantification of drug permeability. These lipids are 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and an equimolar mixture of DMPC/DSPC, both in the absence and in the presence of 33.3 mol% of cholesterol. PAMPA drug permeability using the lipids mentioned above was compared with lecithin-PC. The results show that verapamil permeability depends on the kind of lipid used, in the order DMPC > DMPC/DSPC > DSPC. The permeability of the drugs was between 1.3 and 3.5-times larger than those obtained in lecithin-PC for all the concentrations of the drug used. Naproxen shows similar permeability than verapamil; however, the permeability increased with respect to lecithin-PC only when DMPC and DMPC/DSPC were used. This behavior could be explained by a difference between the drug net charge at pH 7.4. On the other hand, in the presence of cholesterol, verapamil permeability increases in all lipid systems; however, the relative verapamil permeability respect to lecithin-PC did not show any significant increase. This result is likely due to the promoting effect of cholesterol, which is not able to compensate for the large increase in verapamil permeability observed in lecithin-PC. With respect to naproxen, its permeability value and relative permeability respect lecithin-PC not always increased in the presence of cholesterol. This result is probably attributed to the negative charge of naproxen rather than its molecular weight. The lipid systems studied have an advantage in drug permeability quantification, which is mainly related to the charge of the molecule and not to its molecular weight or to cholesterol used as an absorption promoter.

  2. The low-resolution structure of nHDL reconstituted with DMPC with and without cholesterol reveals a mechanism for particle expansion[S

    PubMed Central

    Gogonea, Valentin; Gerstenecker, Gary S.; Wu, Zhiping; Lee, Xavier; Topbas, Celalettin; Wagner, Matthew A.; Tallant, Thomas C.; Smith, Jonathan D.; Callow, Philip; Pipich, Vitaliy; Malet, Hélène; Schoehn, Guy; DiDonato, Joseph A.; Hazen, Stanley L.

    2013-01-01

    Small-angle neutron scattering (SANS) with contrast variation was used to obtain the low-resolution structure of nascent HDL (nHDL) reconstituted with dimyristoyl phosphatidylcholine (DMPC) in the absence and presence of cholesterol, [apoA1:DMPC (1:80, mol:mol) and apoA1:DMPC:cholesterol (1:86:9, mol:mol:mol)]. The overall shape of both particles is discoidal with the low-resolution structure of apoA1 visualized as an open, contorted, and out of plane conformation with three arms in nascent HDL/dimyristoyl phosphatidylcholine without cholesterol (nHDLDMPC) and two arms in nascent HDL/dimyristoyl phosphatidylcholine with cholesterol (nHDLDMPC+Chol). The low-resolution shape of the lipid phase in both nHDLDMPC and nHDLDMPC+Chol were oblate ellipsoids, and fit well within their respective protein shapes. Modeling studies indicate that apoA1 is folded onto itself in nHDLDMPC, making a large hairpin, which was also confirmed independently by both cross-linking mass spectrometry and hydrogen-deuterium exchange (HDX) mass spectrometry analyses. In nHDLDMPC+Chol, the lipid was expanded and no hairpin was visible. Importantly, despite the overall discoidal shape of the whole particle in both nHDLDMPC and nHDLDMPC+Chol, an open conformation (i.e., not a closed belt) of apoA1 is observed. Collectively, these data show that full length apoA1 retains an open architecture that is dictated by its lipid cargo. The lipid is likely predominantly organized as a bilayer with a micelle domain between the open apoA1 arms. The apoA1 configuration observed suggests a mechanism for accommodating changing lipid cargo by quantized expansion of hairpin structures. PMID:23349207

  3. Interactions between DMPC liposomes and the serum blood proteins HSA and IgG.

    PubMed

    Sabín, Juan; Prieto, Gerardo; Ruso, Juan M; Messina, Paula V; Salgado, Francisco J; Nogueira, Montserrat; Costas, Miguel; Sarmiento, Félix

    2009-02-12

    The interaction between two serum blood proteins, namely human serum albumin (HSA) and human immunoglobulin G (IgG), with 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) liposomes has been studied in detail using dynamic light scattering, flow cytometry, enzyme-linked immunosorbent assay (ELISA), electrophoretic mobility, differential scanning calorimetry (DSC), and surface tension measurements. HSA and IgG interact with liposomes forming molecular aggregates that remain stable at protein concentrations beyond those of total liposome coverage. Both HSA and IgG penetrate into the liposome bilayer. An ELISA assay indicates that the Fc region of IgG is the one that is immersed in the DMPC membrane. The liposome-protein interaction is mainly of electrostatic nature, but an important hydrophobic contribution is also present.

  4. Arbutin blocks defects in the ripple phase of DMPC bilayers by changing carbonyl organization.

    PubMed

    Frías, M A; Nicastro, A; Casado, N M C; Gennaro, A M; Díaz, S B; Disalvo, E A

    2007-05-01

    The effect of arbutin, a 4-hydroxyphenyl-beta-glucopyranoside, on dimyristoylphosphatidylcholine (DMPC) bilayers was studied by turbidimetry, EPR and FTIR spectroscopies. The disruption of DMPC multilamellar vesicles (MLV's) with monomyristoylphosphatidylcholine (lysoPC), a product of hydrolysis of phospholipase A(2) (PLA(2)), is more efficient at 18 degrees C, where DMPC MLV's are known to be in the ripple P(beta') phase, than at 10 degrees C (L(beta') flat gel phase). Disruption at 18 degrees C was inhibited by increasing concentrations of arbutin in the solution. This inhibition was correlated with the disappearance of the ripple phase in MLV's when arbutin is present. Shifts in FTIR carbonyl bands caused by arbutin or by temperature changes allow us to propose a model. It is interpreted that the changes in the water-hydrocarbon interface caused by arbutin, forcing a reaccommodation of the carbonyl groups, eliminate the topological defects in the lattice due to mismatches among regions with different area per lipid where lysoPC can insert.

  5. Interfacial behavior of Myristic acid in mixtures with DMPC and Cholesterol

    NASA Astrophysics Data System (ADS)

    Khattari, Z.; Sayyed, M. I.; Qashou, S. I.; Fasfous, I.; Al-Abdullah, T.; Maghrabi, M.

    2017-06-01

    Binary mixture monolayers of Myristic acid (MA) with the same length of saturated acyl chain lipid viz 1,2-myristoyl-sn-glycero-3-phosphocholine (DMPC) and Cholesterol (Chol), were investigated under different experimental conditions using Langmuir monolayers (LMs). The interfacial pressure-area (π-A) isotherms, excess molecular area, excess free energy and fluorescence microscopy (FM) images were recorded at the air/water interface. Monolayers of both systems (e.g. MA/DMPC, MA/Chol) reach the closest acyl hydrophobic chain packing in the range 0.20 < xMA < 0.70. Thermodynamic analysis indicates miscibility of the binary mixtures when spread at the air/water interface with negative deviation from the ideal behavior. Morphological features of MA/DMPC systems were found to depend strongly on MA mole fraction and pressures by showing two extreme minima in Gibbs free energy of mixing, while MA/Chol systems showed only an effective condensing effect at xMA = 0.90. In the whole range of compositions studied here, the liquid-expanded (LE) to liquid-condensed (LC) phase transition occurs at increasing xAM as it accomplished by a huge increase in the inverse compressibility modulus. FM observations confirmed the phase-transition and condensing effects of both mixture monolayers as evidenced by Gibbs free energy of mixing in a limited range of compositions.

  6. Cholesterol Changes the Mechanisms of Aβ Peptide Binding to the DMPC Bilayer.

    PubMed

    Lockhart, Christopher; Klimov, Dmitri K

    2017-10-02

    Using isobaric-isothermal all-atom replica-exchange molecular dynamics (REMD) simulations, we investigated the equilibrium binding of Aβ10-40 monomers to the zwitterionic dimyristoylphosphatidylcholine (DMPC) bilayer containing cholesterol. Our previous REMD simulations, which studied binding of the same peptide to the cholesterol-free DMPC bilayer, served as a control, against which we measured the impact of cholesterol. Our findings are as follows. First, addition of cholesterol to the DMPC bilayer partially expels the Aβ peptide from the hydrophobic core and promotes its binding to bilayer polar headgroups. Using thermodynamic and energetics analyses, we argued that Aβ partial expulsion is not related to cholesterol-induced changes in lateral pressure within the bilayer but is caused by binding energetics, which favors Aβ binding to the surface of the densely packed cholesterol-rich bilayer. Second, cholesterol has a protective effect on the DMPC bilayer structure against perturbations caused by Aβ binding. More specifically, cholesterol reduces bilayer thinning and overall depletion of bilayer density beneath the Aβ binding footprint. Third, we found that the Aβ peptide contains a single cholesterol binding site, which involves hydrophobic C-terminal amino acids (Ile31-Val36), Phe19, and Phe20 from the central hydrophobic cluster, and cationic Lys28 from the turn region. This binding site accounts for about 76% of all Aβ-cholesterol interactions. Because cholesterol binding site in the Aβ10-40 peptide does not contain the GXXXG motif featured in cholesterol interactions with the transmembrane domain C99 of the β-amyloid precursor protein, we argued that the binding mechanisms for Aβ and C99 are distinct reflecting their different conformations and positions in the lipid bilayer. Fourth, cholesterol sharply reduces the helical propensity in the bound Aβ peptide. As a result, cholesterol largely eliminates the emergence of helical structure observed

  7. Conformation and Lipid Binding of a C-Terminal (198-243) Peptide of Human Apolipoprotein A-I (apoA-I)†

    PubMed Central

    Zhu, Hongli L.; Atkinson, David

    2008-01-01

    plasma A-I/DMPC formed under similar conditions: small discoidal complexes (~ 3:1 w/w, ~ 110Å and ~ 1.10g/cm3) formed at initial 1:1 w/w ratio and larger discoidal complexes ( ~ 4.6:1 w/w, ~ 165 Å and ~ 1.085g/cm3) formed at initial 4:1 w/w ratio. The cross-linking of the peptide on the two sizes of disks is consistent with the calculated peptide numbers per particle, which result in sufficient helix to surround the lipid bilayer twice. Thus, our data provide direct evidence that this C-terminal region of apoA-I is responsible for the self-association of apoA-I, and this C-terminal peptide model can mimic the interaction with phospholipid of plasma apoA-I to form two sizes of homogenous discoidal complexes and thus may be responsible for apoA-I function in the formation and maintenance of HDL subspecies in plasma. PMID:17279626

  8. Thermal stabilization of DMPC/DHPC bicelles by addition of cholesterol sulfate

    PubMed Central

    Shapiro, Rebecca A.; Brindley, Amanda J.; Martin, Rachel W.

    2010-01-01

    Doping DMPC/DHPC bicelles with cholesterol sulfate broadens the temperature range over which stable alignment occurs, forming an aligned phase at lower temperatures even with high lipid concentrations. Cholesterol sulfate appears to combine the advantages of cholesterol with those of charged amphiphiles, stabilizing the aligned phase and preventing precipitation. This allows NMR data for RDC and CSA protein structure constraints to be acquired at or below room temperature, an obvious advantage for solid-state and solution studies of heat-sensitive proteins. PMID:20684512

  9. Thermal stabilization of DMPC/DHPC bicelles by addition of cholesterol sulfate.

    PubMed

    Shapiro, Rebecca A; Brindley, Amanda J; Martin, Rachel W

    2010-08-25

    Doping DMPC/DHPC bicelles with cholesterol sulfate broadens the temperature range over which stable alignment occurs, forming an aligned phase at lower temperatures even with high lipid concentrations. Cholesterol sulfate appears to combine the advantages of cholesterol with those of charged amphiphiles, stabilizing the aligned phase and preventing precipitation. This allows NMR data for RDC and CSA protein structure constraints to be acquired at or below room temperature, an obvious advantage for solid-state and solution studies of heat-sensitive proteins.

  10. Interfacial Behavior of Cholesterol, Ergosterol, and Lanosterol in Mixtures with DPPC and DMPC

    PubMed Central

    Sabatini, Karen; Mattila, Juha-Pekka; Kinnunen, Paavo K. J.

    2008-01-01

    Binary mixtures of cholesterol, ergosterol, and lanosterol with phosphatidylcholines differing in the length of the saturated acyl chains, viz 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1-palmitoyl-2-myristoyl-sn-glycero-3-phosphocholine (DMPC), were analyzed using a Langmuir balance for recording force-area (π-A) and surface potential-area (ψ-A) isotherms. A progressive disappearance of the liquid expanded–liquid condensed transition was observed in mixed monolayers with DPPC after the increase in the content of all three sterols. For fluid DMPC matrix, no modulation of the monolayer phase behavior due to the sterols was evident with the exception of lanosterol, for which a pronounced discontinuity between mole fractions of X = 0.3 and X = 0.75 was discernible in the compression isotherms. Condensing and expanding effects in force-area (π-Ā) isotherms due to varying Xsterols and differences in the monolayer physical state were assessed from the values for the interfacial compression moduli. Surface potential measurements support the notion that cholesterol and ergosterol, but not lanosterol, reduce the penetration of water into the lipid monolayers. Examination of the excess free energy of mixing revealed an enhanced stability of binary monolayers containing cholesterol compared to those with ergosterol or lanosterol; the differences are emphasized in the range of surface pressure values found in natural membranes. PMID:18515391

  11. Diffusion of water and selected atoms in DMPC lipid bilayer membranes

    NASA Astrophysics Data System (ADS)

    Hansen, F. Y.; Peters, G. H.; Taub, H.; Miskowiec, A.

    2012-11-01

    Molecular dynamics simulations have been used to determine the diffusion of water molecules as a function of their position in a fully hydrated freestanding 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) bilayer membrane at 303 K and 1 atm. The diffusion rate of water in a ˜10 Å thick layer just outside the membrane surface is reduced on average by a factor of ˜2 relative to bulk. For water molecules penetrating deeper into the membrane, there is an increasing reduction in the average diffusion rate with up to one order of magnitude decrease for those deepest in the membrane. A comparison with the diffusion rate of selected atoms in the lipid molecules shows that ˜6 water molecules per lipid molecule move on the same time scale as the lipids and may therefore be considered to be tightly bound to them. The quasielastic neutron scattering functions for water and selected atoms in the lipid molecule have been simulated and compared to observed quasielastic neutron scattering spectra from single-supported bilayer DMPC membranes.

  12. (1)H and (13)C NMR chemical shifts of methacrylate molecules associated with DMPC and/or DPPC liposomes.

    PubMed

    Fujisawa, Seiichiro; Ishihara, Mariko; Kadoma, Yoshinori

    2005-01-01

    In the light of recent developments, changes in (1)H and (13)C NMR chemical shifts of methacrylate molecule associated with DMPC (L-alpha dimyristoylphosphatidylcholine) or DPPC (L-alpha-dipalmitoylphosphatidylcholine) liposomes as a model for mimic native lipid bilayers were studied at 30, 37, and 52 degrees C. The chemical shifts of 3Ha, 3C, and 4C resonances in methacrylates (see Fig. 2) were greatly shifted higher field, suggesting the methacrylate molecule-lipid bilayer interaction. Comparison of the findings with methyl methacrylate (MMA), ethylene dimethacrylate (EDMA), and triethyleneglycol dimethacrylate (TEGDMA) revealed that the interaction of dimethacrylates (EDMA, TEGDMA) was greater than monomethacrylate, MMA. Their interaction with DMPC liposomes was also judged by a differential scanning calorimetry (DSC), indicating that the interaction was characterized by decreasing the enthalpy, entropy, and transition co-operativity. The evidence of the upfield NMR-shifts for methacrylate molecules was also judged by the descriptors such as the reactivity (HOMO-LUMO energy) and the electrostatic function (partial charges) between methacrylate molecules and DPPC, calculated by a PM 3 semiempirical MO method. The upfield NMR shifts were considerably well interpreted from the descriptors. NMR screening technique in methacrylates to phospholipid targets would be highly valuable in biomaterial developments. Figure 2 Changes in (1)H and (13)C NMR chemical shifts of methacrylate molecule associated with DMPC or DPPC liposomes. DMPC liposomes/MMA (1:1, molar ratio) and DMPC/TEGDMA (1:1) liposomes were measured at 30 degrees C. In DPPC liposome system, the rippled gel phase was measured at 30 degrees C, whereas the liquid crystalline phase for MMA and for both EDMA and TEGDMA were measured at 52 degrees C and 37 degrees C, respectively.

  13. Effect of divalent cations on DMPC/DHPC bicelle formation and alignment.

    PubMed

    Brindley, Amanda J; Martin, Rachel W

    2012-05-22

    Many important classes of biomolecules require divalent cations for optimal activity, making these ions essential for biologically relevant structural studies. Bicelle mixtures composed of short-chain and long-chain lipids are often used in solution- and solid-state NMR structure determination; however, the phase diagrams of these useful orienting media and membrane mimetics are sensitive to other solution components. Therefore, we have investigated the effect of varying concentrations of four divalent cations, Ca(2+), Mg(2+), Zn(2+), and Cd(2+), on cholesterol sulfate-stabilized DMPC/DHPC bicelles. We found that low concentrations of all the divalent ions are tolerated with minimal perturbation. At higher concentrations Zn(2+) and Cd(2+) disrupt the magnetically aligned phase while Ca(2+) and Mg(2+) produce more strongly oriented phases. This result indicates that divalent cations are not only required to maintain the biological activity of proteins and nucleic acids; they may also be used to manipulate the behavior of the magnetically aligned phase.

  14. Constant-pH MD Simulations of DMPA/DMPC Lipid Bilayers.

    PubMed

    Santos, Hugo A F; Vila-Viçosa, Diogo; Teixeira, Vitor H; Baptista, António M; Machuqueiro, Miguel

    2015-12-08

    Current constant-pH molecular dynamics (CpHMD) simulations provide a proper treatment of pH effects on the structure and dynamics of soluble biomolecules like peptides and proteins. However, addressing such effects on lipid membrane assemblies has remained problematic until now, despite the important role played by lipid ionization at physiological pH in a plethora of biological processes. Modeling (de)protonation events in these systems requires a proper consideration of the physicochemical features of the membrane environment, including a sound treatment of solution ions. Here, we apply our recent CpHMD-L method to the study of pH effects on a 25% DMPA/DMPC bilayer membrane model, closely reproducing the correct lipid phases of this system, namely, gel-fluid coexistence at pH 4 and a fluid phase at pH 7. A significant transition is observed for the membrane ionization and mechanical properties at physiological pH, providing a molecular basis for the well-established role of phosphatidic acid (PA) as a key player in the regulation of many cellular events. Also, as reported experimentally, we observed pH-induced PA-PA lipid aggregation at acidic pH. By including the titration of anionic phospholipids, the current methodology makes possible to simulate lipid bilayers with increased realism. To the best of our knowledge, this is the first simulation study dealing with a continuous phospholipid bilayer with pH titration of all constituent lipids.

  15. Atomic detail peptide-membrane interactions: molecular dynamics simulation of gramicidin S in a DMPC bilayer.

    PubMed Central

    Mihailescu, D; Smith, J C

    2000-01-01

    Molecular dynamics simulations have been performed of the sequence-symmetric cyclic decapeptide antibiotic gramicidin S (GS), in interaction with a hydrated dimyristoylphosphatidylcholine (DMPC) bilayer, and the results compared with a "control" simulation of the system in the absence of GS. Following experimental evidence, the GS was initially set in a single antiparallel beta-sheet conformation with two Type II' beta-turns in an amphiphilic interaction with the membrane. This conformation and position remained in the 6.5 ns simulation. Main-chain dihedrals are on average approximately 26 degrees from those determined by NMR experiment on GS in dimethylsulfoxide (DMSO) solution. Sequence-symmetric main-chain and side-chain dihedral angle pairs converge to within approximately 5 degrees and approximately 10 degrees, respectively. The area per lipid, lipid tail order parameters, and quadrupole spin-lattice relaxation times of the control simulation are mostly in good agreement with corresponding experiments. The GS has little effect on the membrane dipole potential or water permeability. However, it is found to have a disordering effect (in agreement with experiment) and a fluidifying effect on lipids directly interacting with it, and an ordering effect on those not directly interacting. PMID:11023880

  16. Experimental and theoretical studies of emodin interacting with a lipid bilayer of DMPC.

    PubMed

    da Cunha, Antonio R; Duarte, Evandro L; Stassen, Hubert; Lamy, M Teresa; Coutinho, Kaline

    2017-09-22

    Emodin is one of the most abundant anthraquinone derivatives found in nature. It is the active principle of some traditional herbal medicines with known biological activities. In this work, we combined experimental and theoretical studies to reveal information about location, orientation, interaction and perturbing effects of Emodin on lipid bilayers, where we have taken into account the neutral form of the Emodin (EMH) and its anionic/deprotonated form (EM(-)). Using both UV/Visible spectrophotometric techniques and molecular dynamics (MD) simulations, we showed that both EMH and EM(-) are located in a lipid membrane. Additionally, using MD simulations, we revealed that both forms of Emodin are very close to glycerol groups of the lipid molecules, with the EMH inserted more deeply into the bilayer and more disoriented relative to the normal of the membrane when compared with the EM(-), which is more exposed to interfacial water. Analysis of several structural properties of acyl chains of the lipids in a hydrated pure DMPC bilayer and in the presence of Emodin revealed that both EMH and EM(-) affect the lipid bilayer, resulting in a remarkable disorder of the bilayer in the vicinity of the Emodin. However, the disorder caused by EMH is weaker than that caused by EM(-). Our results suggest that these disorders caused by Emodin might lead to distinct effects on lipid bilayers including its disruption which are reported in the literature.

  17. Direct comparison of elastic incoherent neutron scattering experiments with molecular dynamics simulations of DMPC phase transitions.

    PubMed

    Aoun, Bachir; Pellegrini, Eric; Trapp, Marcus; Natali, Francesca; Cantù, Laura; Brocca, Paola; Gerelli, Yuri; Demé, Bruno; Marek Koza, Michael; Johnson, Mark; Peters, Judith

    2016-04-01

    Neutron scattering techniques have been employed to investigate 1,2-dimyristoyl-sn -glycero-3-phosphocholine (DMPC) membranes in the form of multilamellar vesicles (MLVs) and deposited, stacked multilamellar-bilayers (MLBs), covering transitions from the gel to the liquid phase. Neutron diffraction was used to characterise the samples in terms of transition temperatures, whereas elastic incoherent neutron scattering (EINS) demonstrates that the dynamics on the sub-macromolecular length-scale and pico- to nano-second time-scale are correlated with the structural transitions through a discontinuity in the observed elastic intensities and the derived mean square displacements. Molecular dynamics simulations have been performed in parallel focussing on the length-, time- and temperature-scales of the neutron experiments. They correctly reproduce the structural features of the main gel-liquid phase transition. Particular emphasis is placed on the dynamical amplitudes derived from experiment and simulations. Two methods are used to analyse the experimental data and mean square displacements. They agree within a factor of 2 irrespective of the probed time-scale, i.e. the instrument utilized. Mean square displacements computed from simulations show a comparable level of agreement with the experimental values, albeit, the best match with the two methods varies for the two instruments. Consequently, experiments and simulations together give a consistent picture of the structural and dynamical aspects of the main lipid transition and provide a basis for future, theoretical modelling of dynamics and phase behaviour in membranes. The need for more detailed analytical models is pointed out by the remaining variation of the dynamical amplitudes derived in two different ways from experiments on the one hand and simulations on the other.

  18. Direct comparison of elastic incoherent neutron scattering experiments with molecular dynamics simulations of DMPC phase transitions

    SciTech Connect

    Aoun, Bachir; Pellegrini, Eric; Trapp, Marcus; Natali, Francesca; Cantù, Laura; Brocca, Paola; Gerelli, Yuri; Demé, Bruno; Koza, Michael Marek; Johnson, Mark; Peters, Judith

    2016-04-01

    Neutron scattering techniques have been employed to investigate 1,2-dimyristoyl-sn-glycero-3- phosphocholine (DMPC) membranes in the form of multilamellar vesicles (MLVs) and deposited, stacked multilamellar-bilayers (MLBs), covering transitions from the gel to the liquid phase. Neutron diffraction was used to characterise the samples in terms of transition temperatures, whereas elastic incoherent neutron scattering (EINS) demonstrates that the dynamics on the sub-macromolecular length-scale and pico- to nano-second time-scale are correlated with the structural transitions through a discontinuity in the observed elastic intensities and the derived mean square displacements. Molecular dynamics simulations have been performed in parallel focussing on the length-, time- and temperature-scales of the neutron experiments. They correctly reproduce the structural features of the main gel-liquid phase transition. Particular emphasis is placed on the dynamical amplitudes derived from experiment and simulations. Two methods are used to analyse the experimental data and mean square displacements. They agree within a factor of 2 irrespective of the probed time-scale, i.e. the instrument utilized. Mean square displacements computed from simulations show a comparable level of agreement with the experimental values, albeit, the best match with the two methods varies for the two instruments. Consequently, experiments and simulations together give a consistent picture of the structural and dynamical aspects of the main lipid transition and provide a basis for future, theoretical modelling of dynamics and phase behaviour in membranes. The need for more detailed analytical models is pointed out by the remaining variation of the dynamical amplitudes derived in two different ways from experiments on the one hand and simulations on the other.

  19. Temperature-dependent neutron diffraction measurements from D2O hydrating single-supported lipid bilayers of DMPC

    NASA Astrophysics Data System (ADS)

    Buck, Z. N.; Torres, J.; Mazza, A.; Kaiser, H.; Taub, H.; Hansen, F. Y.; Miskowiec, A.; Tyagi, M.

    The freezing point depression of water associated with biological membranes, studied principally by NMR, has been of interest for decades. Here we have used neutron diffraction measurements at the University of Missouri Research Reactor (MURR) to investigate the freezing behavior of water associated with single-supported zwitterionic lipid bilayers composed of DMPC. Diffraction patterns obtained as a function of temperature reveal that water freezes abruptly into its hexagonal phase at 270 K with no evidence of amorphous ice. Following the initial crystallization of the membrane-associated water there is a region of continuous hexagonal crystal growth, which is believed to occur in the interfacial water closest to the membrane. The temperature-dependent intensity of the observed Bragg peaks have been compared with that of incoherently elastically-scattered neutrons collected on the High-Flux Backscattering Spectrometer at NIST from an identical sample hydrated with H2O [2]. We find excellent agreement between the two data sets, suggesting the absence of amorphous solid water and that all the water hydrating a DMPC membrane eventually freezes into the hexagonal crystalline phase. 2 M. Bai et al., Europhys. Lett. 98, 48006 (2012). Supported by NSF Grant Nos. DMR-0944772 and DGE-1069091.

  20. Measurement of the Membrane Dipole Electric Field in DMPC Vesicles Using Vibrational Shifts of p-Cyanophenylalanine and Molecular Dynamics Simulations

    PubMed Central

    Shrestha, Rebika; Cardenas, Alfredo E.; Elber, Ron; Webb, Lauren J.

    2015-01-01

    The magnitude of the membrane dipole field was measured using vibrational Stark effect (VSE) shifts of nitrile oscillators placed on the unnatural amino acid p-cyanophenylalanine (p-CN-Phe) added to a peptide sequence at four unique positions. These peptides, which were based on a repeating alanine-leucine motif, intercalated into small unilamellar DMPC vesicles which formed an α-helix as confirmed by circular dichroic (CD) spectroscopy. Molecular dynamics simulations of the membrane-intercalated helix containing two of the nitrile probes, one near the head-group region of the lipid (αLAX(25)) and one buried in the interior of the bilayer (αLAX(16)), were used to examine the structure of the nitrile with respect to the membrane normal, the assumed direction the dipole field, by quantifying both a small tilt of the helix in the bilayer and conformational rotation of the p-CN-Phe side chain at steady-state. Vibrational absorption energies of the nitrile oscillator at each position showed a systematic blue shift as the nitrile was stepped towards the membrane interior; for several different concentrations of peptide, the absorption energy of the nitrile located in the middle of the bilayer was ~3 cm−1 greater than that of the nitrile closest to the surface of the membrane. Taken together, the measured VSE shifts and nitrile orientations within the membrane resulted in a value of 8 – 11 MV/cm for the dipole field, at the high end of the range of possible values that have been accumulated from a variety of indirect measurements. Implications for this are discussed. PMID:25602635

  1. Single Molecule Lateral Mobility and Membrane Organization in DMPC/Cholesterol Mixtures at the Air-Water Interface

    NASA Astrophysics Data System (ADS)

    Shaikh, Saame; Stillwell, William; Naumann, Christoph

    2002-03-01

    To better understand the lipid heterogeneity of biological membranes, we have studied the lateral mobility and membrane organization of DMPC and cholesterol (Chol) mixtures at the air-water interface using single molecule fluorescence imaging and epifluorescence microscopy. The single molecule imaging technique was used to track the lateral diffusion of single molecules of TRITC-DPPE or cholesteryl Bodipy. In the absence of Chol, mean square displacement histograms obtained from single molecule tracking of TRITC-DPPE show unobstructed diffusion. Including Chol at low levels of Chol (<10 moldiffusion at intermediate levels ( 30 molof Chol (>40 molmacroscopic phase separations. Data obtained from tracking experiments of cholesteryl-Bodipy also show complementary changes in diffusion. Our results indicate that our techniques provide insight into the micro and macro organization of lipid domains at the air-water interface.

  2. Molecular dynamics simulations and experimental studies of binding and mobility of 7-tert-butyldimethylsilyl-10-hydroxycamptothecin and its 20(S)-4-aminobutyrate ester in DMPC membranes.

    PubMed

    Xiang, Tian-Xiang; Jiang, Zhi-Qiang; Song, Lin; Anderson, Bradley D

    2006-01-01

    The enhanced permeability and retention of liposomes in solid tumors makes liposomal formulations attractive for the targeting of various antitumor agents. This study explores the binding, orientation, and dynamic properties of a potent topoisomerase I inhibitor, 7-tert-butyldimethylsilyl-10-hydroxycamptothecin (DB-67), and its 20(S)-4-aminobutyrate ester prodrug (DB-67-AB) in DMPC liposomes by molecular dynamics (MD) simulations and experimental studies. MD simulations of an all-atom and fully hydrated liquid-crystalline bilayer (2 x 36 DMPC lipids) containing single molecules of DB-67 and DB-67-AB were conducted for up to 50 ns. Membrane/water partition coefficients for DB-67 and DB-67-AB vs pH were determined by ultracentrifugation. Fluorescence spectra and/or steady-state anisotropies were measured in various solvents and in DMPC liposomes. Kinetics for the reversible DB-67 lactone ring-opening in the presence and absence of DMPC liposomes were determined by HPLC with fluorescence detection. During the entire simulation time both DB-67 and DB-67-AB were located on the bilayer membrane near the polar ester groups of DMPC. The average depth of penetration for DB-67 and DB-67-AB was similar (12.4-13.2 A) with the prodrug's protonated amino group strongly solvated by surface water and lipid phosphate groups. Binding and fluorescence experiments revealed only a modest reduction in the binding affinity upon attachment of the ionized 4-aminobutyrate group onto DB-67. The binding microenvironment polarity resembles that of a polar solvent such as EtOH and DMSO. Kinetics experiments confirmed that DB-67 lactone hydrolysis is inhibited in the presence of DMPC liposomes, consistent with the reduced exposure of its lactone ring to water, as observed in the simulations. Both bound DB-67 and bound DB-67-AB have nonrandom orientations and reduced mobility in the membrane, especially for diffusion normal to the bilayer surface, and rotational relaxation, both of which are > or

  3. E/M dips. Evidence for lipids regularly distributed into hexagonal super-lattices in pyrene-PC/DMPC binary mixtures at specific concentrations.

    PubMed Central

    Tang, D.; Chong, P. L.

    1992-01-01

    We have examined the effect of 1-palmitoyl-2-(10-pyrenyl)decanoyl-sn-glycerol-3-phosphatidylcholine (Pyr-PC) concentration on the ratio of excimer fluorescence to monomer fluorescence (E/M) in L-alpha-dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles at 30 degrees C, with special attention focussed on the smoothness of the curve. We observed a series of dips, in addition to kinks, in the plot of E/M versus the mole fraction of Pyr-PC (XPyrPC). The observation of dips is a new finding, perhaps unique for Pyr-PC in DMPC since only kinks were observed for Pyr-PC in L-alpha-dipalmitoylphosphatidylcholine (DPPC) and in egg yolk phosphatidylcholine (egg-PC) (Somerharju et al., 1985. Biochemistry. 24: 2773-2781). The dips/kinks observed here are distributed according to a well defined pattern reflecting a lateral order in the membrane, and distributed symmetrically with respect to 50 mol% Pyr-PC. Some of the dips appear at specific concentrations (YPyrPC) according to the hexagonal super-lattice model proposed by Virtanen et al. (1988. J. Mol. Electr. 4: 233-236). However, the observations of dips at XPyrPC > 66.7 mol% and the kink at 33.3 mol% cannot be interpreted by the model of Virtanen et al. (1988). These surprising results can be understood by virtue of an extended hexagonal super-lattice model, in which we have proposed that if the pyrene-containing acyl chains are regularly distributed as a hexagonal super-lattice in the DMPC matrix at a specific concentration YPyrPC, then the acyl chains of DMPC can form a regularly distributed hexagonal super-lattice in the membrane at a critical concentration (1-YPyrPC). The excellent agreement between the calculated and the observed dip/kink positions, except for the dip at 74 mol% and the kink at 40 mol%, provides most compelling evidence that lipids are regularly distributed into hexagonal super-lattices in Pyr-PC/DMPC mixtures at specific concentrations. The physical nature of the dips not only gives us a better

  4. E/M dips. Evidence for lipids regularly distributed into hexagonal super-lattices in pyrene-PC/DMPC binary mixtures at specific concentrations.

    PubMed

    Tang, D; Chong, P L

    1992-10-01

    We have examined the effect of 1-palmitoyl-2-(10-pyrenyl)decanoyl-sn-glycerol-3-phosphatidylcholine (Pyr-PC) concentration on the ratio of excimer fluorescence to monomer fluorescence (E/M) in L-alpha-dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles at 30 degrees C, with special attention focussed on the smoothness of the curve. We observed a series of dips, in addition to kinks, in the plot of E/M versus the mole fraction of Pyr-PC (XPyrPC). The observation of dips is a new finding, perhaps unique for Pyr-PC in DMPC since only kinks were observed for Pyr-PC in L-alpha-dipalmitoylphosphatidylcholine (DPPC) and in egg yolk phosphatidylcholine (egg-PC) (Somerharju et al., 1985. Biochemistry. 24: 2773-2781). The dips/kinks observed here are distributed according to a well defined pattern reflecting a lateral order in the membrane, and distributed symmetrically with respect to 50 mol% Pyr-PC. Some of the dips appear at specific concentrations (YPyrPC) according to the hexagonal super-lattice model proposed by Virtanen et al. (1988. J. Mol. Electr. 4: 233-236). However, the observations of dips at XPyrPC > 66.7 mol% and the kink at 33.3 mol% cannot be interpreted by the model of Virtanen et al. (1988). These surprising results can be understood by virtue of an extended hexagonal super-lattice model, in which we have proposed that if the pyrene-containing acyl chains are regularly distributed as a hexagonal super-lattice in the DMPC matrix at a specific concentration YPyrPC, then the acyl chains of DMPC can form a regularly distributed hexagonal super-lattice in the membrane at a critical concentration (1-YPyrPC). The excellent agreement between the calculated and the observed dip/kink positions, except for the dip at 74 mol% and the kink at 40 mol%, provides most compelling evidence that lipids are regularly distributed into hexagonal super-lattices in Pyr-PC/DMPC mixtures at specific concentrations. The physical nature of the dips not only gives us a better

  5. Ionic strength and composition govern the elasticity of biological membranes. A study of model DMPC bilayers by force- and transmission IR spectroscopy.

    PubMed

    Šegota, Suzana; Vojta, Danijela; Pletikapić, Galja; Baranović, Goran

    2015-02-01

    Infrared (IR) spectroscopy was used to quantify the ion mixture effect of seawater (SW), particularly the contribution of Mg(2+) and Ca(2+) as dominant divalent cations, on the thermotropic phase behaviour of 1,2-dimyristoyl-sn-glycero-3-posphocholine (DMPC) bilayers. The changed character of the main transition at 24 °C from sharp to gradual in films and the 1 °C shift of the main transition temperature in dispersions reflect the interactions of lipid headgroups with the ions in SW. Force spectroscopy was used to quantify the nanomechanical hardness of a DMPC supported lipid bilayer (SLB). Considering the electrostatic and ion binding equilibrium contributions while systematically probing the SLB in various salt solutions, we showed that ionic strength had a decisive influence on its nanomechanics. The mechanical hardness of DMPC SLBs in the liquid crystalline phase linearly increases with the increasing fraction of all ion-bound lipids in a series of monovalent salt solutions. It also linearly increases in the gel phase but almost three times faster (the corresponding slopes are 4.9 nN/100 mM and 13.32 nN/100 mM, respectively). We also showed that in the presence of divalent ions (Ca(2+) and Mg(2+)) the bilayer mechanical hardness was unproportionally increased, and that was accompanied with the decrease of Na(+) ion and increase of Cl(-) ion bound lipids. The underlying process is a cooperative and competitive ion binding in both the gel and the liquid crystalline phase. Bilayer hardness thus turned out to be very sensitive to ionic strength as well as to ionic composition of the surrounding medium. In particular, the indicated correlation helped us to emphasize the colligative properties of SW as a naturally occurring complex ion mixture.

  6. A <i>yigP mutant strain is a small colony variant of E. coli, and shows pleiotropic antibiotic resistance.

    PubMed

    Xia, Hui; Tang, Qiongwei; Song, Jie; Ye, Jiang; Wu, Haizhen; Zhang, Huizhan

    2017-09-15

    Small colony variants (SCVs) are a commonly observed subpopulation of bacteria that have a small colony size and distinctive biochemical characteristics. SCVs are more resistant to some antibiotics than the wild-type, and usually cause persistent infections in the clinic. SCV studies have been very active during the past two decades, especially of Staphylococcus aureus. However, fewer studies on Escherichia coli SCVs exist, so we studied an E. coli SCV during an experiment involving the deletion of the yigP locus. PCR and DNA sequencing revealed that the SCV was attributable to a defect in the yigP function. Furthermore, we investigated the antibiotic resistance profile of the SCV and it showed increased erythromycin, kanamycin and D-cycloserine resistance, but collateral sensitivity to ampicillin, polymyxin, chloramphenicol, tetracycline, rifampin, and nalidixic acid. We tried to determine the association between yigP and the pleiotropic antibiotic resistance of the SCV by analyzing biofilm formation, cellular morphology and coenzyme Q (Q8) production. Our results indicated that impaired Q8 biosynthesis was the primary factor that contributed to the increased resistance and collateral sensitivity of the SCV. This study offers a novel genetic basis for E. coli SCVs and an insight into the development of alternative antimicrobial strategies for clinical therapy.

  7. Glycerosomes: Investigation of role of 1,2-dimyristoyl-sn-glycero-3-phosphatidycholine (DMPC) on the assembling and skin delivery performances.

    PubMed

    Manca, Maria Letizia; Manconi, Maria; Zaru, Marco; Valenti, Donatella; Peris, Jose Esteban; Matricardi, Pietro; Maccioni, Anna Maria; Fadda, Anna Maria

    2017-10-30

    Glycerosomes were formulated using 1,2-dimyristoyl-sn-glycero-3-phosphatidycholine (DMPC), diclofenac sodium salt and 10, 20 or 30% glycerol in the water phase, while corresponding liposomes were prepared with the same amount of DMPC and diclofenac, without glycerol. The aim of the present work was to evaluate the effect of the used phospholipid on vesicle features and ability to favour diclofenac skin deposition by comparing these results with those found in previous works performed using hydrogenated soy phosphatidylcholine (P90H) and dipalmitoylphosphatidylcholine (DPPC). Liposomes and glycerosomes were multilamellar, liposomes being smaller (72±6nm). Interactions among glycerol, phospholipids and drug led to the formation of a non-rigid bilayer structure and a variation of the main transition temperature, which shifted to lower temperature. The addition of glycerol led to the formation of more viscous systems (from ∼2.5mPa/s for basic liposomes to ∼5mPa/s for glycerosomes), which improved spread ability of the formulations on the skin.Results obtained in vitro were promising using glycerosomes, irrespective of the amount of glycerol used: the amount of drug, which accumulated into and permeated through the different skin strata, was high and comparable with that obtained using P90H, suggesting that glycerosomes may represent an efficient carrier for both local effect or systemic absorption. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Investigation of the structure of unilamellar dimyristoylphosphatidylcholine vesicles in aqueous sucrose solutions by small-angle neutron and X-ray scattering

    SciTech Connect

    Kiselev, M. A. Zemlyanaya, E. V.; Zhabitskaya, E. I.; Aksenov, V. L.

    2015-01-15

    The structure of a polydispersed population of unilamellar dimyristoylphosphatidylcholine (DMPC) vesicles in sucrose solutions has been investigated by small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS). Calculations within the model of separated form factors (SFF) show that the structure of the vesicle system depends strongly on the sucrose concentration.

  9. Incorporation of antimicrobial peptides into membranes: a combined liquid-state NMR and molecular dynamics study of alamethicin in DMPC/DHPC bicelles.

    PubMed

    Dittmer, Jens; Thøgersen, Lea; Underhaug, Jarl; Bertelsen, Kresten; Vosegaard, Thomas; Pedersen, Jan M; Schiøtt, Birgit; Tajkhorshid, Emad; Skrydstrup, Troels; Nielsen, Niels Chr

    2009-05-14

    Detailed insight into the interplay between antimicrobial peptides and biological membranes is fundamental to our understanding of the mechanism of bacterial ion channels and the action of these in biological host-defense systems. To explore this interplay, we have studied the incorporation, membrane-bound structure, and conformation of the antimicrobial peptide alamethicin in lipid bilayers using a combination of 1H liquid-state NMR spectroscopy and molecular dynamics (MD) simulations. On the basis of experimental NMR data, we evaluate simple in-plane and transmembrane incorporation models as well as pore formation for alamethicin in DMPC/DHPC (1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine/1,2-dihexanoyl-sn-glycero-3-phosphatidylcholine) bicelles. Peptide-lipid nuclear Overhauser effect (NOE) and paramagnetic relaxation enhancement (PRE) data support a transmembrane configuration of the peptide in the bilayers, but they also reveal that the system cannot be described by a single simple conformational model because there is a very high degree of dynamics and heterogeneity in the three-component system. To explore the origin of this heterogeneity and dynamics, we have compared the NOE and PRE data with MD simulations of an ensemble of alamethicin peptides in a DMPC bilayer. From all-atom MD simulations, the contacts between peptide, lipid, and water protons are quantified over a time interval up to 95 ns. The MD simulations provide a statistical base that reflects our NMR data and even can explain some initially surprising NMR results concerning specific interactions between alamethicin and the lipids.

  10. What can we learn about the lipid vesicle structure from the small-angle neutron scattering experiment?

    PubMed

    Kiselev, M A; Zemlyanaya, E V; Aswal, V K; Neubert, R H H

    2006-08-01

    Small-angle neutron scattering (SANS) on the unilamellar vesicle (ULV) populations (diameter 500 and 1,000 A) in D2O was used to characterize lipid vesicles from dimyristoylphosphatidylcholine (DMPC) at three phases: gel Lbeta', ripple Pbeta' and liquid Lalpha. Parameters of vesicle populations and internal structure of the DMPC bilayer were characterized on the basis of the separated form factor (SFF) model. Vesicle shape changes from nearly spherical in the Lalpha phase to elliptical in the Pbeta' and Lbeta' phases. This is true for vesicles prepared via extrusion through pores with the diameter 500 A. Parameters of the internal bilayer structure (thickness of the membrane and the hydrophobic core, hydration and the surface area of the lipid molecule) were determined on the basis of the hydrophobic-hydrophilic (HH) approximation of neutron scattering length density across the bilayer rhox and of the step function (SF) approximation of rhox. DMPC membrane thickness in the Lalpha phase (T = 30 degrees C) demonstrates a dependence on the membrane curvature for extruded vesicles. Prepared via extrusion through 500 A diameter pores, vesicle population in the Lalpha phase has the following characteristics: average value of minor semi-axis 266 +/- 2 A, ellipse eccentricity 1.11 +/- 0.02, polydispersity 26%, thickness of the membrane 48.9 +/- 0.2 A and of the hydrophobic core 19.9 +/- 0.4 A, surface area 60.7 +/- 0.5 A2 and number of water molecules 12.8 +/- 0.3 per DMPC molecule. Vesicles prepared via extrusion through pores with the diameter 1,000 A have polydispersity of 48% and membrane thickness of 45.5 +/- 0.6 A in the Lalpha phase. SF approximation was used to describe the DMPC membrane structure in Lbeta' (T = 10 degrees C) and Pbeta' (T = 20 degrees C) phases. Extruded DMPC vesicles in D2O have membrane thickness of 49.6 +/- 0.5 A in the Lbeta' phase and 48.3 +/- 0.6 A in the Pbeta' phase. The dependence of the DMPC membrane thickness on temperature was restored

  11. SFF analysis of the small angle scattering data for investigation of a vesicle systems structure

    NASA Astrophysics Data System (ADS)

    Zemlyanaya, E. V.; Kiselev, M. A.; Zhabitskaya, E. I.; Gruzinov, A. Yu.; Aksenov, V. L.; Ipatova, O. M.; Druzhilovskaya, O. S.

    2016-06-01

    Experimental data on the small angle synchrotron X-ray scattering (SAXS) are analyzed on a basis of Separated form factors method (SFF) for a study of the drug delivery Phospholipid Transport Nano System (PTNS). Basic parameters of polydispersed population of PTNS nanoparticles (average radius of PTNS-particles, polydispersity of radius, thickness of membrane) have been determined. The results are discussed in comparison with the SFF results for the “classical” vesicular system of dimyristoylphosphocholine (DMPC).

  12. Reconciling structural and thermodynamic predictions using all-atom and coarse-grain force fields: the case of charged oligo-arginine translocation into DMPC bilayers.

    PubMed

    Hu, Yuan; Sinha, Sudipta Kumar; Patel, Sandeep

    2014-10-16

    Using the translocation of short, charged cationic oligo-arginine peptides (mono-, di-, and triarginine) from bulk aqueous solution into model DMPC bilayers, we explore the question of the similarity of thermodynamic and structural predictions obtained from molecular dynamics simulations using all-atom and Martini coarse-grain force fields. Specifically, we estimate potentials of mean force associated with translocation using standard all-atom (CHARMM36 lipid) and polarizable and nonpolarizable Martini force fields, as well as a series of modified Martini-based parameter sets. We find that we are able to reproduce qualitative features of potentials of mean force of single amino acid side chain analogues into model bilayers. In particular, modifications of peptide-water and peptide-membrane interactions allow prediction of free energy minima at the bilayer-water interface as obtained with all-atom force fields. In the case of oligo-arginine peptides, the modified parameter sets predict interfacial free energy minima as well as free energy barriers in almost quantitative agreement with all-atom force field based simulations. Interfacial free energy minima predicted by a modified coarse-grained parameter set are -2.51, -4.28, and -5.42 for mono-, di-, and triarginine; corresponding values from all-atom simulations are -0.83, -3.33, and -3.29, respectively, all in units of kcal/mol. We found that a stronger interaction between oligo-arginine and the membrane components and a weaker interaction between oligo-arginine and water are crucial for producing such minima in PMFs using the polarizable CG model. The difference between bulk aqueous and bilayer center states predicted by the modified coarse-grain force field are 11.71, 14.14, and 16.53 kcal/mol, and those by the all-atom model are 6.94, 8.64, and 12.80 kcal/mol; those are of almost the same order of magnitude. Our simulations also demonstrate a remarkable similarity in the structural aspects of the ensemble of

  13. Reconciling Structural and Thermodynamic Predictions Using All-Atom and Coarse-Grain Force Fields: The Case of Charged Oligo-Arginine Translocation into DMPC Bilayers

    PubMed Central

    2015-01-01

    Using the translocation of short, charged cationic oligo-arginine peptides (mono-, di-, and triarginine) from bulk aqueous solution into model DMPC bilayers, we explore the question of the similarity of thermodynamic and structural predictions obtained from molecular dynamics simulations using all-atom and Martini coarse-grain force fields. Specifically, we estimate potentials of mean force associated with translocation using standard all-atom (CHARMM36 lipid) and polarizable and nonpolarizable Martini force fields, as well as a series of modified Martini-based parameter sets. We find that we are able to reproduce qualitative features of potentials of mean force of single amino acid side chain analogues into model bilayers. In particular, modifications of peptide–water and peptide–membrane interactions allow prediction of free energy minima at the bilayer–water interface as obtained with all-atom force fields. In the case of oligo-arginine peptides, the modified parameter sets predict interfacial free energy minima as well as free energy barriers in almost quantitative agreement with all-atom force field based simulations. Interfacial free energy minima predicted by a modified coarse-grained parameter set are −2.51, −4.28, and −5.42 for mono-, di-, and triarginine; corresponding values from all-atom simulations are −0.83, −3.33, and −3.29, respectively, all in units of kcal/mol. We found that a stronger interaction between oligo-arginine and the membrane components and a weaker interaction between oligo-arginine and water are crucial for producing such minima in PMFs using the polarizable CG model. The difference between bulk aqueous and bilayer center states predicted by the modified coarse-grain force field are 11.71, 14.14, and 16.53 kcal/mol, and those by the all-atom model are 6.94, 8.64, and 12.80 kcal/mol; those are of almost the same order of magnitude. Our simulations also demonstrate a remarkable similarity in the structural aspects of

  14. Small angle X-ray scattering and 31P NMR studies on the phase behavior of phospholipid bilayered mixed micelles

    NASA Astrophysics Data System (ADS)

    Bolze, Jörg; Fujisawa, Tetsuro; Nagao, Takashi; Norisada, Kazushi; Saitô, Hazime; Naito, Akira

    2000-10-01

    The phase behavior of lipid bilayered micelles (`bicelles') (dimyristoyl-phosphatidylcholine, DMPC/dihexanoyl-phosphatidyl-choline, DHPC 2.6/1) has been studied by small angle X-ray scattering and 31P NMR. Below 3% w/v the bilayers are arranged in tightly packed stacks. At intermediate concentrations single units are observed, whereas at 24% w/v and higher, weak stacking occurs again. The DMPC/DHPC ratio in the bicelles strongly increases at low concentration, which is correlated with an increase in the bicelle size and stacking. The increase of the order parameter in a magnetic field is related to the stack formation. Below 297 K there is no stacking at any concentration and no magnetic alignment.

  15. Growth Kinetics of Lipid-Based Nanodiscs to Unilamellar Vesicles: A Time-Resolved Small Angle Neutron Scattering (SANS) Study

    SciTech Connect

    Mahabir, Suanne; Small, Darcy; Li, Ming; Wan, Wankei; Kucerka, Norbert; Littrell, Ken; Katsaras, John; Nieh, Mu-Ping

    2013-01-01

    Mixtures of dimyristoyl-phosphatidylcholine (DMPC), dimyristoyl-phosphatidylglycerol (DMPG) and dihexanoylphosphatidylcholine (DHPC) in aqueous solutions spontaneously form monodisperse, bilayered nanodiscs (also known as bicelles ) at or below the melting transition temperature of DMPC (TM ~23 C). In dilute systems above the main transition temperature TM of DMPC, bicelles coalesce (increasing their diameter) and eventually self-fold into unilamellar vesicles (ULVs). Time resolved small angle neutron scattering was used to study the growth kinetics of nanodiscs below and equal to TM over a period of hours as a function of temperature at two lipid concentrations in presence or absence of NaCl salt. Bicelles seem to undergo a sudden initial growth phase with increased temperature, which is then followed by a slower reaction-limited growth phase that depends on ionic strength, lipid concentration and temperature. The bicelle interaction energy was derived from the colloidal theory of Derjaguin and Landau, and Verwey and Overbeek (DLVO). While the calculated total energy between discs is attractive and proportional to their growth rate, a more detailed mechanism is proposed to describe the mechanism of disc coalescence. After annealing at low temperature (low-T), samples were heated to 50 C in order to promote the formation of ULVs. Although the low-T annealing of samples has only a marginal effect on the mean size of end-state ULVs, it does affect their polydispersity, which increases with increased T, presumably driven by the entropy of the system.

  16. ApoA-I mimetics.

    PubMed

    Stoekenbroek, R M; Stroes, E S; Hovingh, G K

    2015-01-01

    A wealth of evidence indicates that plasma levels of high-density lipoprotein cholesterol (HDL-C) are inversely related to the risk of cardiovascular disease (CVD). Consequently, HDL-C has been considered a target for therapy in order to reduce the residual CVD burden that remains significant, even after application of current state-of-the-art medical interventions. In recent years, however, a number of clinical trials of therapeutic strategies that increase HDL-C levels failed to show the anticipated beneficial effect on CVD outcomes. As a result, attention has begun to shift toward strategies to improve HDL functionality, rather than levels of HDL-C per se. ApoA-I, the major protein component of HDL, is considered to play an important role in many of the antiatherogenic functions of HDL, most notably reverse cholesterol transport (RCT), and several therapies have been developed to mimic apoA-I function, including administration of apoA-I, mutated variants of apoA-I, and apoA-I mimetic peptides. Based on the potential anti-inflammatory effects, apoA-I mimetics hold promise not only as anti-atherosclerotic therapy but also in other therapeutic areas.

  17. Membrane interactions in small fast-tumbling bicelles as studied by 31P NMR.

    PubMed

    Bodor, Andrea; Kövér, Katalin E; Mäler, Lena

    2015-03-01

    Small fast-tumbling bicelles are ideal for studies of membrane interactions at molecular level; they allow analysis of lipid properties using solution-state NMR. In the present study we used 31P NMR relaxation to obtain detailed information on lipid head-group dynamics. We explored the effect of two topologically different membrane-interacting peptides on bicelles containing either dimyristoylphosphocholine (DMPC), or a mixture of DMPC and dimyristoylphosphoglycerol (DMPG), and dihexanoylphosphocholine (DHPC). KALP21 is a model transmembrane peptide, designed to span a DMPC bilayer and dynorphin B is a membrane surface active neuropeptide. KALP21 causes significant increase in bicelle size, as evidenced by both dynamic light scattering and 31P T2 relaxation measurements. The effect of dynorphin B on bicelle size is more modest, although significant effects on T2 relaxation are observed at higher temperatures. A comparison of 31P T1 values for the lipids with and without the peptides showed that dynorphin B has a greater effect on lipid head-group dynamics than KALP21, especially at elevated temperatures. From the field-dependence of T1 relaxation data, a correlation time describing the overall lipid motion was derived. Results indicate that the positively charged dynorphin B decreases the mobility of the lipid molecules--in particular for the negatively charged DMPG--while KALP21 has a more modest influence. Our results demonstrate that while a transmembrane peptide has severe effects on overall bilayer properties, the surface bound peptide has a more dramatic effect in reducing lipid head-group mobility. These observations may be of general importance for understanding peptide-membrane interactions. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Morphology of fast-tumbling bicelles: a small angle neutron scattering and NMR study.

    PubMed

    Luchette, P A; Vetman, T N; Prosser, R S; Hancock, R E; Nieh, M P; Glinka, C J; Krueger, S; Katsaras, J

    2001-08-06

    Bilayered micelles, or bicelles, which consist of a mixture of long- and short-chain phospholipids, are a popular model membrane system. Depending on composition, concentration, and temperature, bicelle mixtures may adopt an isotropic phase or form an aligned phase in magnetic fields. Well-resolved (1)H NMR spectra are observed in the isotropic or so-called fast-tumbling bicelle phase, over the range of temperatures investigated (10-40 degrees C), for molar ratios of long-chain lipid to short-chain lipid between 0.20 and 1.0. Small angle neutron scattering data of this phase are consistent with the model in which bicelles were proposed to be disk-shaped. The experimentally determined dimensions are roughly consistent with the predictions of R.R. Vold and R.S. Prosser (J. Magn. Reson. B 113 (1996)). Differential paramagnetic shifts of head group resonances of dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC), induced by the addition of Eu(3+), are also consistent with the bicelle model in which DHPC is believed to be primarily sequestered to bicelle rims. Selective irradiation of the DHPC aliphatic methyl resonances results in no detectable magnetization transfer to the corresponding DMPC methyl resonances (and vice versa) in bicelles, which also suggests that DHPC and DMPC are largely sequestered in the bicelle. Finally, (1)H spectra of the antibacterial peptide indolicidin (ILPWKWPWWPWRR-NH(2)) are compared, in a DPC micellar phase and the above fast-tumbling bicellar phases for a variety of compositions. The spectra exhibit adequate resolution and improved dispersion of amide and aromatic resonances in certain bicelle mixtures.

  19. Unprecedented observation of days-long remnant orientation of phospholipid bicelles: a small-angle X-ray scattering and theoretical study.

    PubMed

    Loudet-Courreges, Cécile; Nallet, Frédéric; Dufourc, Erick J; Oda, Reiko

    2011-08-02

    Nanometric bilayer-based self-assembled micelles commonly named as bicelles, formed with a mixture of long and short chains phosphatidylcholine lipids (PC), are known to orient spontaneously in a magnetic field. This field-induced orientational order strongly depends on the molecular structure of the phospholipids. Using small-angle X-ray scattering (SAXS), we performed detailed structural studies of bicelles and investigated the orientation/relaxation kinetics in three different systems: saturated-chain lipid bicelles made of DMPC (dimyristoyl PC)/DCPC (1,2-dicaproyl PC) with and without the added paramagnetic lanthanide ions Eu(3+), as well as bicelles of TBBPC (1-tetradecanoyl-2-(4-(4-biphenyl)butanoyl)-sn-glycero-3-PC)/DCPC. The structural study confirmed the previous NMR studies, which showed that DMPC bicelles orient with the membrane normal perpendicular (defined here as "nematic" orientation) to the magnetic field, whereas they orient parallel (defined here as "smectic" orientation) to the magnetic field in the presence of Eu(3+). The TBBPC bicelles also show smectic orientation. Surprisingly, the orientational order induced in the magnetic field remains even after the magnetic field is removed, which allowed us to investigate the orientation and relaxation kinetics of different bicelle structures. We demonstrate that this kinetics is very different for all three types of bicelles at the same lipid concentration; DMPC bicelles (~40 nm diameter) with and without Eu(3+) orient faster than TBBPC bicelles (~80 nm diameter). However, for the relaxation, DMPC bicelles (nematic) lose their macroscopic orientation only after one hour, whereas both DMPC bicelles with Eu(3+) and TBBPC bicelles (smectic) remarkably stay oriented for up to several days! These results indicate that the orientation mechanism of these nanometric disks in the magnetic field is governed by their size, with smaller bicelles orienting faster than the larger bicelles. Their relaxation

  20. Small-Angle Neutron Scattering and Spontaneous Formation of Unilamellar Vesicles: Potential Vehicles for Drug Delivery

    NASA Astrophysics Data System (ADS)

    Katsaras, John

    2004-03-01

    Unilamellar vesicles (ULVs) are single-bilayer shells with radii commonly between 10 and 100 nm, and are widely used as model membranes, drug delivery systems, microreactors and substrates for a variety of enzymes and proteins. A common method of making ULVs is the extrusion of multilamellar vesicles (MLVs) through synthetic membranes of known pore size. These extruded ULVs are invariably unstable and in due time, revert back to MLVs. Over the years there have been reports of the spontaneous formation of stable ULVs in surfactant, lipid, and lipid/detergent mixtures. These ULVs have sometimes been shown to be monodisperse and their radii were found, almost without exception, to vary with concentration. We have carried-out small-angle neutron scattering (SANS) experiments on a biomimetic system composed of the phospholipids dimyristoyl and dihexanoyl phosphorylcholine (DMPC and DHPC, respectively). Doping DMPC/DHPC multilamellar vesicles with either the negatively charged lipid dimyristoyl phosphorylglycerol (DMPG, net charge -1) or the divalent cation, calcium (Ca2+) leads to the spontaneous formation of monodisperse unilamellar vesicles whose radii are concentration independent, in contrast to previous experimental observations.

  1. Kinetics of the barotropic ripple (P beta')/lamellar liquid crystal (L alpha) phase transition in fully hydrated dimyristoylphosphatidylcholine (DMPC) monitored by time-resolved x-ray diffraction.

    PubMed

    Caffrey, M; Hogan, J; Mencke, A

    1991-08-01

    We present here the first study of the use of a pressure-jump to induce the ripple (P beta')/lamellar liquid crystal (L alpha) phase transition in fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). The transition was monitored by using time-resolved x-ray diffraction (TRXRD). Applying a pressure-jump from atmospheric to 11.3 MPa (1640 psig, 111.6 atm) in 2.5 s induces the L alpha to P beta' phase transition which takes place in two stages. The lamellar repeat spacing initially increases from a value of 66.0 +/- 0.1 A (n = 4) to a maximum value of 70.3 +/- 0.8 A (n = 4) after 10 s and after a further 100-150 s decreases slightly to 68.5 +/- 0.3 A (n = 4). The reverse transition takes place following a pressure jump in 5.5 s from 11.3 MPa to atmospheric pressure. Again, the transition occurs in two stages with the repeat spacing steadily decreasing from an initial value of 68.5 +/- 0.3 A (n = 3) to a minimum value of 66.6 +/- 0.3 A (n = 3) after 50 s and then increasing by approximately 0.5 A over a period of 100 s. The transition temperature increases linearly with pressure up to 14.1 MPa in accordance with the Clapeyron relation, giving a dT/dP value of 0.285 degrees C/MPa (28.5 degrees C/kbar) and an associated volume change of 40 microliters/g. A dynamic compressibility of 0.13 +/- 0.01 A/MPa has been determined for the L alpha phase. This value is compared with the equilibrium compressibilities of bilayer and nonbilayer phases reported in the literature. The results suggest testable mechanisms for the pressure-induced transition involving changes in periodicity, phase hydration, chain order, and orientation. A more complete understanding of the transition mechanism will require improvement in detector spatial resolution and sensitivity, and data on the pressure sensitivity of phase hydration.

  2. Kinetics of the barotropic ripple (P beta')/lamellar liquid crystal (L alpha) phase transition in fully hydrated dimyristoylphosphatidylcholine (DMPC) monitored by time-resolved x-ray diffraction.

    PubMed Central

    Caffrey, M; Hogan, J; Mencke, A

    1991-01-01

    We present here the first study of the use of a pressure-jump to induce the ripple (P beta')/lamellar liquid crystal (L alpha) phase transition in fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). The transition was monitored by using time-resolved x-ray diffraction (TRXRD). Applying a pressure-jump from atmospheric to 11.3 MPa (1640 psig, 111.6 atm) in 2.5 s induces the L alpha to P beta' phase transition which takes place in two stages. The lamellar repeat spacing initially increases from a value of 66.0 +/- 0.1 A (n = 4) to a maximum value of 70.3 +/- 0.8 A (n = 4) after 10 s and after a further 100-150 s decreases slightly to 68.5 +/- 0.3 A (n = 4). The reverse transition takes place following a pressure jump in 5.5 s from 11.3 MPa to atmospheric pressure. Again, the transition occurs in two stages with the repeat spacing steadily decreasing from an initial value of 68.5 +/- 0.3 A (n = 3) to a minimum value of 66.6 +/- 0.3 A (n = 3) after 50 s and then increasing by approximately 0.5 A over a period of 100 s. The transition temperature increases linearly with pressure up to 14.1 MPa in accordance with the Clapeyron relation, giving a dT/dP value of 0.285 degrees C/MPa (28.5 degrees C/kbar) and an associated volume change of 40 microliters/g. A dynamic compressibility of 0.13 +/- 0.01 A/MPa has been determined for the L alpha phase. This value is compared with the equilibrium compressibilities of bilayer and nonbilayer phases reported in the literature. The results suggest testable mechanisms for the pressure-induced transition involving changes in periodicity, phase hydration, chain order, and orientation. A more complete understanding of the transition mechanism will require improvement in detector spatial resolution and sensitivity, and data on the pressure sensitivity of phase hydration. PMID:1912281

  3. Free Cholesterol Determines rHDL Phospholipid Phase Structure and Stability

    PubMed Central

    Auton, Matthew; Bassett, G. Randall; Gillard, Baiba K.; Pownall, Henry J.

    2013-01-01

    Reassembled high density lipoproteins (rHDL) of various sizes and compositions containing apo A-I or apo A-II as their sole protein, dimyristoyl phosphatidylcholine (DMPC), and various amounts of free cholesterol (FC) have been isolated and analyzed by differential scanning calorimetry (DSC) and by circular dichroism to determine their stability and the temperature dependence of their helical content. Our data show that the multiple rHDL species obtained at each mol% FC usually do not have the same mole% FC as the starting mixture and that the size of the multiple species increases in a quantized way with their respective mol% FC. DSC studies reveal multiple phases or domains that can be classified as virtual DMPC, which contains a small amount of DMPC that slightly reduces the melting temperature Tm, a boundary phase that is adjacent to the apo A-I or apo A-II that circumscribes the discoidal rHDL, and a mixed FC + DMPC phase that has a Tm that increases with mol% FC. Only the large rHDL contain virtual DMPC whereas all contain boundary phase and various amounts of mixed FC + DMPC according to increasing size and mol% FC. As reported by others, FC stabilizes the rHDL. For rHDL (apo A-II) compared to rHDL (apo A-I), this occurs in spite of the reduced number of helical regions that mediate binding to the DMPC surface. This effect is attributed to the very high lipophilicity of apo A-II and the reduction in the polarity of the interface between DMPC and the aqueous phase with increasing mol% FC, an effect that is expected to increase the hydrophobic associations with the non polar face of the amphipathic helices of apo A-II. These data are relevant to the differential effects of FC and apolipoprotein species on intracellular and plasma membrane nascent HDL assembly and subsequent remodeling by plasma proteins. PMID:23721456

  4. Growth kinetics of lipid-based nanodiscs to unilamellar vesicles-a time-resolved small angle neutron scattering (SANS) study.

    PubMed

    Mahabir, Suanne; Small, Darcy; Li, Ming; Wan, Wankei; Kučerka, Norbert; Littrell, Kenneth; Katsaras, John; Nieh, Mu-Ping

    2013-03-01

    Mixtures of dimyristoyl-phosphatidylcholine (DMPC), dimyristoyl-phosphatidylglycerol (DMPG) and dihexanoyl-phosphatidylcholine (DHPC) in aqueous solutions spontaneously form monodisperse, bilayered nanodiscs (also known as "bicelles") at or below the melting transition temperature of DMPC (T(M) ~23°C). In dilute systems above the main transition temperature T(M) of DMPC, bicelles coalesce (increasing their diameter) and eventually self-fold into unilamellar vesicles (ULVs). Time-resolved small angle neutron scattering was used to study the growth kinetics of nanodiscs below and equal to T(M) over a period of hours as a function of temperature at two lipid concentrations in presence or absence of NaCl salt. Bicelles seem to undergo a sudden initial growth phase with increased temperature, which is then followed by a slower reaction-limited growth phase that depends on ionic strength, lipid concentration and temperature. The bicelle interaction energy was derived from the colloidal theory of Derjaguin and Landau, and Verwey and Overbeek (DLVO). While the calculated total energy between discs is attractive and proportional to their growth rate, a more detailed mechanism is proposed to describe the mechanism of disc coalescence. After annealing at low temperature (low-T), samples were heated to 50°C in order to promote the formation of ULVs. Although the low-T annealing of samples has only a marginal effect on the mean size of end-state ULVs, it does affect their polydispersity, which increases with increased T, presumably driven by the entropy of the system. Published by Elsevier B.V.

  5. Small angle x-ray scattering study of the interaction of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymers with lipid bilayers.

    SciTech Connect

    Firestone, M. A.; Wolf, A. C.; Seifert, S.; Univ. Chicago

    2003-11-01

    The relationship between molecular architecture and the nature of interactions with lipid bilayers has been studied for a series of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers using small-angle X-ray scattering (SAXS) and thermal analysis (differential scanning calorimetry, DSC). The number of molecular repeat units in the hydrophobic poly(propylene oxide), PPO, block has been found to be a critical determinant of the nature of triblock copolymer-lipid bilayer association. For dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based biomembrane structures, polymers possessing a PPO chain length commensurate with the acyl chain dimensions of the lipid bilayer yield highly ordered, swollen lamellar structures consistent with well-integrated (into the lipid bilayer) PPO blocks. Triblock copolymers of lesser PPO chain length yield materials with structural characteristics similar to a simple dispersion of DMPC in water. Increasing the concentration (from 4 to 12 mol %) of well-integrated triblock copolymers enhances the structural ordering of the lamellar phase, while concentrations exceeding 16 mol % result in the formation of a hexagonal phase. Examination of temperature-induced changes in the structure of these mesophases (complex fluids) reveals that if the temperature is reduced sufficiently, all compositions exclude polymer and thus exhibit the characteristic SAXS pattern for hydrated DMPC bilayers. Increasing the temperature promotes better insertion of the polymers possessing PPO chain lengths sufficient for membrane insertion. No temperature-induced structural changes are observed in compositions prepared with PEO-PPO-PEO polymers that feature PPO length insufficient to permit full incorporation into the lipid bilayer.

  6. Myeloperoxidase-mediated Methionine Oxidation Promotes an Amyloidogenic Outcome for Apolipoprotein A-I*

    PubMed Central

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

    2015-01-01

    High plasma levels of apolipoprotein A-I (apoA-I) correlate with cardiovascular health, whereas dysfunctional apoA-I is a cause of atherosclerosis. In the atherosclerotic plaques, amyloid deposition increases with aging. Notably, apoA-I is the main component of these amyloids. Recent studies identified high levels of oxidized lipid-free apoA-I in atherosclerotic plaques. Likely, myeloperoxidase (MPO) secreted by activated macrophages in atherosclerotic lesions is the promoter of such apoA-I oxidation. We hypothesized that apoA-I oxidation by MPO levels similar to those present in the artery walls in atherosclerosis can promote apoA-I structural changes and amyloid fibril formation. ApoA-I was exposed to exhaustive chemical (H2O2) oxidation or physiological levels of enzymatic (MPO) oxidation and incubated at 37 °C and pH 6.0 to induce fibril formation. Both chemically and enzymatically oxidized apoA-I produced fibrillar amyloids after a few hours of incubation. The amyloid fibrils were composed of full-length apoA-I with differential oxidation of the three methionines. Met to Leu apoA-I variants were used to establish the predominant role of oxidation of Met-86 and Met-148 in the fibril formation process. Importantly, a small amount of preformed apoA-I fibrils was able to seed amyloid formation in oxidized apoA-I at pH 7.0. In contrast to hereditary amyloidosis, wherein specific mutations of apoA-I cause protein destabilization and amyloid deposition, oxidative conditions similar to those promoted by local inflammation in atherosclerosis are sufficient to transform full-length wild-type apoA-I into an amyloidogenic protein. Thus, MPO-mediated oxidation may be implicated in the mechanism that leads to amyloid deposition in the atherosclerotic plaques in vivo. PMID:25759391

  7. Temperature dependence of the ripple structure in dimyristoylphosphatidylcholine studied by synchrotron X-ray small-angle diffraction.

    PubMed

    Matuoka, S; Kato, S; Akiyama, M; Amemiya, Y; Hatta, I

    1990-10-05

    The ripple structure of 1,2-dimyristoyl-L-phosphatidylcholine (DMPC) multibilayer containing excess water (60 wt%) was studied by synchrotron X-ray small-angle diffraction. The (0,1) spacing which corresponds to the ripple repeat distance depends on temperature: At 13 degrees C the (0,1) spacing is 14.15 nm, the spacing decreases at higher temperatures and reaches 12.1 nm at 23.5 degrees C, just below the main transition temperature. The spacing is in good agreement between heating process and cooling process except for the supercooling region. The result suggests that the rearrangement of the ripple structure takes place during temperature change successively. The Landau-de Gennes free energy equation explains well the temperature dependence of the ripple repeat distance.

  8. Inhibition of apolipoprotein A-I gene expression by obesity-associated endocannabinoids.

    PubMed

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

    2012-04-01

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

  9. Bilayer thickness and lipid interface area in unilamellar extruded 1,2-diacylphosphatidylcholine liposomes: a small-angle neutron scattering study.

    PubMed

    Balgavý, P; Dubnicková, M; Kucerka, N; Kiselev, M A; Yaradaikin, S P; Uhríková, D

    2001-05-02

    Small-angle neutron scattering (SANS) experiments have been performed on large unilamellar liposomes prepared from 1,2-dilauroylphosphatidylcholine (DLPC), 1,2-dimyristoyl-phosphatidylcholine (DMPC) and 1,2-distearoylphosphatidylcholine (DSPC) in heavy water by extrusion through polycarbonate filters with 500 A pores. The neutron scattering intensity I(Q) in the region of scattering vectors Q corresponding to 0.0015 A(-2) < or = Q(2) < or = 0.0115 A(-2) was fitted using a step function model of bilayer neutron scattering length density and supposing that the liposomes are spherical and have a Gaussian distribution of radii. Using the lipid volumetric data, and supposing that the thickness of bilayer polar region equals to d(H) = 9+/-1 A and the water molecular volume intercalated in the bilayer polar region is the same as in the aqueous bulk aqueous phase, the steric bilayer thickness d(L), the lipid surface area A(L) and the number of water molecules per lipid molecule N intercalated in the bilayer polar region were obtained: d(L) = 41.58+/-1.93 A, A(L) = 57.18+/-1.00 A(2) and N = 6.53+/-1.93 in DLPC at 20 degrees C, d(L) = 44.26+/-1.42 A, A(L) = 60.01+/-0.75 A(2) and N = 7.37+/-1.94 in DMPC at 36 degrees C, and d(L) = 49.77+/-1.52 A, A(L) = 64.78+/-0.46 A(2) and N = 8.67+/-1.97 in DSPC at 60 degrees C. After correcting for area thermal expansivity alpha approximately 0.00417 K(-1), the lipid surface area shows a decrease with the lipid acyl chain length at 60 degrees C: A(L) = 67.56+/-1.18 A(2) in DLPC, A(L) = 66.33+/-0.83 A(2) in DMPC and A(L) = 64.78+/-0.46 A(2) in DSPC. It is also shown that a joint evaluation of SANS and small-angle X-ray scattering on unilamellar liposomes can be used to obtain the value of d(H) and the distance of the lipid phosphate group from the bilayer hydrocarbon region d(H1).

  10. Apolipoprotein A-I modulates regulatory T cells in autoimmune LDLr-/-, ApoA-I-/- mice.

    PubMed

    Wilhelm, Ashley J; Zabalawi, Manal; Owen, John S; Shah, Dharika; Grayson, Jason M; Major, Amy S; Bhat, Shaila; Gibbs, Dwayne P; Thomas, Michael J; Sorci-Thomas, Mary G

    2010-11-12

    The immune system is complex, with multiple layers of regulation that serve to prevent the production of self-antigens. One layer of regulation involves regulatory T cells (Tregs) that play an essential role in maintaining peripheral self-tolerance. Patients with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis have decreased levels of HDL, suggesting that apoA-I concentrations may be important in preventing autoimmunity and the loss of self-tolerance. In published studies, hypercholesterolemic mice lacking HDL apoA-I or LDLr(-/-), apoA-I(-/-) (DKO), exhibit characteristics of autoimmunity in response to an atherogenic diet. This phenotype is characterized by enlarged cholesterol-enriched lymph nodes (LNs), as well as increased T cell activation, proliferation, and the production of autoantibodies in plasma. In this study, we investigated whether treatment of mice with lipid-free apoA-I could attenuate the autoimmune phenotype. To do this, DKO mice were first fed an atherogenic diet containing 0.1% cholesterol, 10% fat for 6 weeks, after which treatment with apoA-I was begun. Subcutaneous injections of 500 μg of lipid-free apoA-I was administered every 48 h during the treatment phase. These and control mice were maintained for an additional 6 weeks on the diet. At the end of the 12-week study, DKO mice showed decreased numbers of LN immune cells, whereas Tregs were proportionately increased. Accompanying this increase in Tregs was a decrease in the percentage of effector/effector memory T cells. Furthermore, lipid accumulation in LN and skin was reduced. These results suggest that treatment with apoA-I reduces inflammation in DKO mice by augmenting the effectiveness of the LN Treg response.

  11. Myeloperoxidase-mediated Methionine Oxidation Promotes an Amyloidogenic Outcome for Apolipoprotein A-I.

    PubMed

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

    2015-04-24

    High plasma levels of apolipoprotein A-I (apoA-I) correlate with cardiovascular health, whereas dysfunctional apoA-I is a cause of atherosclerosis. In the atherosclerotic plaques, amyloid deposition increases with aging. Notably, apoA-I is the main component of these amyloids. Recent studies identified high levels of oxidized lipid-free apoA-I in atherosclerotic plaques. Likely, myeloperoxidase (MPO) secreted by activated macrophages in atherosclerotic lesions is the promoter of such apoA-I oxidation. We hypothesized that apoA-I oxidation by MPO levels similar to those present in the artery walls in atherosclerosis can promote apoA-I structural changes and amyloid fibril formation. ApoA-I was exposed to exhaustive chemical (H2O2) oxidation or physiological levels of enzymatic (MPO) oxidation and incubated at 37 °C and pH 6.0 to induce fibril formation. Both chemically and enzymatically oxidized apoA-I produced fibrillar amyloids after a few hours of incubation. The amyloid fibrils were composed of full-length apoA-I with differential oxidation of the three methionines. Met to Leu apoA-I variants were used to establish the predominant role of oxidation of Met-86 and Met-148 in the fibril formation process. Importantly, a small amount of preformed apoA-I fibrils was able to seed amyloid formation in oxidized apoA-I at pH 7.0. In contrast to hereditary amyloidosis, wherein specific mutations of apoA-I cause protein destabilization and amyloid deposition, oxidative conditions similar to those promoted by local inflammation in atherosclerosis are sufficient to transform full-length wild-type apoA-I into an amyloidogenic protein. Thus, MPO-mediated oxidation may be implicated in the mechanism that leads to amyloid deposition in the atherosclerotic plaques in vivo. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Small game

    Treesearch

    John C. Kilgo

    2005-01-01

    Although small game currently is not harvested on the Savannah river Site(SRS) soutside of the Crackerneck Wildlife Management area and logical Reserve (CWMA), several species of small game occur on SRS. these include snipe (Gallinago gallinago), American woodcock (Scolopax minor), morning dove (Zenaida macroura...

  13. Francisella tularensis subsp. tularensis Group A.I, United States

    PubMed Central

    Birdsell, Dawn N.; Johansson, Anders; Öhrman, Caroline; Kaufman, Emily; Molins, Claudia; Pearson, Talima; Gyuranecz, Miklós; Naumann, Amber; Vogler, Amy J.; Myrtennäs, Kerstin; Larsson, Pär; Forsman, Mats; Sjödin, Andreas; Gillece, John D.; Schupp, James; Petersen, Jeannine M.; Keim, Paul

    2014-01-01

    We used whole-genome analysis and subsequent characterization of geographically diverse strains using new genetic signatures to identify distinct subgroups within Francisella tularensis subsp. tularensis group A.I: A.I.3, A.I.8, and A.I.12. These subgroups exhibit complex phylogeographic patterns within North America. The widest distribution was observed for A.I.12, which suggests an adaptive advantage. PMID:24755401

  14. Free cholesterol determines reassembled high-density lipoprotein phospholipid phase structure and stability.

    PubMed

    Auton, Matthew; Bassett, G Randall; Gillard, Baiba K; Pownall, Henry J

    2013-06-25

    Reassembled high-density lipoproteins (rHDL) of various sizes and compositions containing apo A-I or apo A-II as their sole protein, dimyristoylphosphatidylcholine (DMPC), and various amounts of free cholesterol (FC) have been isolated and analyzed by differential scanning calorimetry (DSC) and by circular dichroism to determine their stability and the temperature dependence of their helical content. Our data show that the multiple rHDL species obtained at each FC mole percent usually do not have the same FC mole percent as the starting mixture and that the size of the multiple species increases in a quantized way with their respective FC mole percent. DSC studies reveal multiple phases or domains that can be classified as virtual DMPC, which contains a small amount of DMPC that slightly reduces the melting temperature (Tm), a boundary phase that is adjacent to the apo A-I or apo A-II that circumscribes the discoidal rHDL, and a mixed FC/DMPC phase that has a Tm that increases with FC mole percent. Only the large rHDL contain virtual DMPC, whereas all contain boundary phase and various amounts of the mixed FC/DMPC phase according to increasing size and FC mole percent. As reported by others, FC stabilizes the rHDL. For rHDL (apo A-II) compared to rHDL (apo A-I), this occurs in spite of the reduced number of helical regions that mediate binding to the DMPC surface. This effect is attributed to the very high lipophilicity of apo A-II and the reduction in the polarity of the interface between DMPC and the aqueous phase with an increasing FC mole percent, an effect that is expected to increase the strength of the hydrophobic associations with the nonpolar face of the amphipathic helices of apo A-II. These data are relevant to the differential effects of FC and apolipoprotein species on intracellular and plasma membrane nascent HDL assembly and subsequent remodeling by plasma proteins.

  15. Small Magnetometer

    NASA Technical Reports Server (NTRS)

    Kuhnke, Falko; Musmann, Gunter; Glassmeier, K. H.; Tsurutani, Bruce

    1995-01-01

    Small, lightweight, low-power magnetometer measures three-dimensional magnetic field. Includes three toroidal cores - one for each dimension. Exhibits high sensitivity, low zero-point drift, and low noise. Magnetometer circuit includes driver circuit and three analog signal-processing circuits. Output of analog signal-processing circuit proportional to one of components of external magnetic field.

  16. Different effects of propofol and nitrosopropofol on DMPC multilamellar liposomes.

    PubMed

    Momo, Federico; Fabris, Sabrina; Bindoli, Alberto; Scutari, Guido; Stevanato, Roberto

    2002-02-19

    The mechanisms of reaction of propofol with nitrosoglutathione lead to the formation of an active species which was identified, and then synthesised, as 2,6-diisopropyl-4-nitrosophenol. In the present work, we demonstrate the in vitro formation of 2,6-diisopropyl-4-nitrosophenol, then we discuss the interaction of propofol and 2,6-diisopropyl-4-nitrosophenol with dimyristoylphosphatidylcholine and egg yolk phosphatidylcholine multilamellar liposomes using differential scanning calorimetry and spin labelling techniques. It was demonstrated that both molecules are highly lipophylic and absorb almost entirely in the lipid phase. The thermotropic profiles showed that these molecules affect the temperature and the co-operativity of the gel-to-fluid state transition of the liposomes differently: the effects of 2,6-diisopropylphenol on the lipid organisation are quite similar to phenol and coherently interpretable in terms of the disorder produced in the membrane by a bulky group; 2,6-diisopropyl-4-nitrosophenol is a stronger perturbing agent, and ESR spectra suggest that this is due to a relative accumulation of the molecule into the interfacial region of the bilayer.

  17. Structure of the DMPC lipid bilayer ripple phase†

    PubMed Central

    Akabori, Kiyotaka; Nagle, John F.

    2014-01-01

    High resolution structure is presented for the ripple (Pβ′) phase of the phospholipid dimyristoylphosphatidylcholine. Low angle X-ray scattering from oriented samples yielded 57 orders, more than twice as many as recorded previously. The determined electron density map has a sawtooth profile similar to the result from lower resolution data, but the features are sharper allowing better estimates for the modulated bilayer profile and the distribution of headgroups along the aqueous interface. Analysis of high resolution wide angle X-ray data shows that the hydrocarbon chains in the longer, major side of the asymmetric sawtooth are packed similarly to the LβF gel phase, with chains in both monolayers coupled and tilted by 18° in the same direction. The absence of Bragg rods that could be associated with the minor side is consistent with disordered chains, as often suggested in the literature. However, the new high resolution bilayer profile strongly suggests that the chains in the two monolayers in the minor side and the curved region are not in registry. This staggered monolayer modulated melting suggests a direction for improving theories of the ripple phase. PMID:25503248

  18. Modeling DMPC lipid membranes with SIRAH force-field.

    PubMed

    Barrera, Exequiel E; Frigini, Ezequiel N; Porasso, Rodolfo D; Pantano, Sergio

    2017-08-10

    Coarse-grained simulation schemes are increasingly gaining popularity in the scientific community because of the significant speed up granted, allowing a considerable expansion of the accessible time and size scales accessible to molecular simulations. However, the number of compatible force fields capable of representing ensembles containing different molecular species (i.e., Protein, DNA, etc) is still limited. Here, we present a set of parameters and simplified representation for lipids compatible with the SIRAH force field for coarse-grained simulations ( http://www.sirahff.com ). We show that the present model not only achieves a correct reproduction of structural parameters as area per lipid and thickness, but also dynamic descriptors such as diffusion coefficient, order parameters, and proper temperature driven variations. Adding phospholipid membranes to the existing aqueous solution, protein and DNA representations of the SIRAH force field permit considering the most common problems tackled by the biomolecular simulation community.

  19. Expression of the C-terminal domain of human apolipoprotein A-I using a chimeric apolipoprotein.

    PubMed

    Sallee, Daniel E; Horn, James V C; Fuentes, Lukas A; Weers, Paul M M

    2017-09-01

    Human apolipoprotein A-I (apoA-I) is the most abundant protein in high-density lipoprotein, an anti-atherogenic lipid-protein complex responsible for reverse cholesterol transport. The protein is composed of an N-terminal helix bundle domain, and a small C-terminal (CT) domain. To facilitate study of CT-apoA-I, a novel strategy was employed to produce this small domain in a bacterial expression system. A protein construct was designed of insect apolipophorin III (apoLp-III) and residues 179-243 of apoA-I, with a unique methionine residue positioned between the two proteins and an N-terminal His-tag to facilitate purification. The chimera was expressed in E. coli, purified by Ni-affinity chromatography, and cleaved by cyanogen bromide. SDS-PAGE revealed the presence of three proteins with masses of 7 kDa (CT-apoA-I), 18 kDa (apoLp-III), and a minor 26 kDa band of uncleaved chimera. The digest was reloaded on the Ni-affinity column to bind apoLp-III and uncleaved chimera, while CT-apoA-I was washed from the column and collected. Alternatively, CT-apoA-I was isolated from the digest by reversed-phase HPLC. CT-apoA-I was α-helical, highly effective in solubilizing phospholipid vesicles and disaggregating LPS micelles. However, CT-apoA-I was less active compared to full-length apoA-I in protecting lipolyzed low density lipoproteins from aggregating, and disrupting phosphatidylglycerol bilayer vesicles. Thus the novel expression system produced mg quantities of functional CT-apoA-I, facilitating structural and functional studies of this critical domain of apoA-I. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Deceptively Small

    NASA Image and Video Library

    2015-02-02

    Tiny Epimetheus is dwarfed by adjacent slivers of the A and F rings. But is it really? Looks can be deceiving! There is approximately 10 to 20 times more mass in that tiny dot than in the piece of the A ring visible in this image! In total, Saturn's rings have about as much mass as a few times the mass of the moon Mimas. (This mass estimate comes from measuring the waves raised in the rings by moons like Epimetheus.) The rings look physically larger than any moon because the individual ring particles are very small, giving them a large surface area for a given mass. Epimetheus (70 miles or 113 kilometers across), on the other hand, has a small surface area per mass compared to the rings, making it look deceptively small. This view looks toward the sunlit side of the rings from about 19 degrees above the ringplane. The image was taken in visible light with the Cassini spacecraft narrow-angle camera on Dec. 5, 2014. The view was obtained at a distance of approximately 1.2 million miles (2 million kilometers) from Epimetheus and at a Sun-Epimetheus-spacecraft, or phase, angle of 40 degrees. Image scale is 7 miles (12 kilometers) per pixel. http://photojournal.jpl.nasa.gov/catalog/PIA18302

  1. Surface plasmon resonance analysis of the mechanism of binding of apoA-I to high density lipoprotein particles

    PubMed Central

    Lund-Katz, Sissel; Nguyen, David; Dhanasekaran, Padmaja; Kono, Momoe; Nickel, Margaret; Saito, Hiroyuki; Phillips, Michael C.

    2010-01-01

    The partitioning of apolipoprotein A-I (apoA-I) molecules in plasma between HDL-bound and -unbound states is an integral part of HDL metabolism. We used the surface plasmon resonance (SPR) technique to monitor in real time the reversible binding of apoA-I to HDL. Biotinylated human HDL2 and HDL3 were immobilized on a streptavidin-coated SPR sensor chip, and apoA-I solutions at different concentrations were flowed across the surface. The wild-type (WT) human and mouse apoA-I/HDL interaction involves a two-step process; apoA-I initially binds to HDL with fast association and dissociation rates, followed by a step exhibiting slower kinetics. The isolated N-terminal helix bundle domains of human and mouse apoA-I also exhibit a two-step binding process, consistent with the second slower step involving opening of the helix bundle domain. The results of fluorescence experiments with pyrene-labeled apoA-I are consistent with the N-terminal helix bundle domain interacting with proteins resident on the HDL particle surface. Dissociation constants (Kd) measured for WT human apoA-I interactions with HDL2 and HDL3 are about 10 µM, indicating that the binding is low affinity. This Kd value does not apply to all of the apoA-I molecules on the HDL particle but only to a relatively small, labile pool. PMID:19786567

  2. Investigation of the interaction of dimethyl sulfoxide with lipid membranes by small-angle neutron scattering

    SciTech Connect

    Gorshkova, J. E. Gordeliy, V. I.

    2007-05-15

    The influence of dimethyl sulfoxide (CH{sub 3}){sub 2}SO (DMSO) on the structure of membranes of 1,2-dimiristoyl-sn-glycero-3-phosphatidylcholine (DMPC) in an excess of a water-DMSO solvent is investigated over a wide range of DMSO molar concentrations 0.0 {<=} X{sub DMSO} {<=} 1.0 at temperatures T = 12.5 and 55 deg. C. The dependences of the repeat distance d of multilamellar membranes and the thickness d{sub b} of single vesicles on the molar concentration X{sub DMSO} in the L{sub {beta}}{sub '} gel and L{sub {alpha}} liquid-crystalline phases are determined by small-angle neutron scattering. The intermembrane distance d{sub s} is determined from the repeat distance d and the membrane thickness d{sub b}. It is shown that an increase in the molar concentration X{sub DMSO} leads to a considerable decrease in the intermembrane distance and that, at X{sub DMSO} = 0.4, the neighboring membranes are virtually in steric contact with each other. The use of the deuterated phospholipid (DMSO-D6) and the contrast variation method makes it possible, for the first time, to determine the number of DMSO molecules strongly bound to the membrane.

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

    PubMed Central

    Getz, Godfrey S; Reardon, Catherine A

    2011-01-01

    Cardiovascular disease remains a major cause of morbidity and mortality in the westernized world. Atherosclerosis is the underlying cause of most cardiovascular diseases. Atherosclerosis is a slowly evolving chronic inflammatory disorder involving the intima of large and medium sized arteries that is initiated in response to high plasma lipid levels, especially LDL. Cells of both the innate and adaptive immunity are involved in this chronic inflammation. Although high plasma LDL levels are a major contributor to most stages of the evolution of atherosclerosis, HDL and its major protein apoA-I possess properties that attenuate and may even reverse atherosclerosis. Two major functions are the ability to induce the efflux of cholesterol from cells, particularly lipid-loaded macrophages, in the artery wall for transfer to the liver, a process referred to as reverse cholesterol transport, and the ability to attenuate the pro-inflammatory properties of LDL. The removal of cellular cholesterol from lipid-loaded macrophages may also be anti-inflammatory. One of the most promising therapies to enhance the anti-atherogenic, anti-inflammatory properties of HDL is apoA-I mimetic peptides. Several of these peptides have been shown to promote cellular cholesterol efflux, attenuate the production of pro-inflammatory cytokines by macrophages, and to attenuate the pro-inflammatory properties of LDL. This latter effect may be related to their high affinity for oxidized lipids present in LDL. This review discusses the functional properties of the peptides and their effect on experimental atherosclerosis and the results of initial clinical studies in humans. PMID:22096372

  4. Enthalpy-driven apolipoprotein A-I and lipid bilayer interaction indicating protein penetration upon lipid binding.

    PubMed

    Arnulphi, Cristina; Jin, Lihua; Tricerri, M Alejandra; Jonas, Ana

    2004-09-28

    The interaction of lipid-free apolipoprotein A-I (apoA-I) with small unilamellar vesicles (SUVs) of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) with and without free cholesterol (FC) was studied by isothermal titration calorimetry and circular dichroism spectroscopy. Parameters reported are the affinity constant (K(a)), the number of protein molecules bound per vesicle (n), enthalpy change (DeltaH degrees), entropy change (DeltaS degrees ), and the heat capacity change (DeltaC(p) degrees). The binding process of apoA-I to SUVs of POPC plus 0-20% (mole) FC was exothermic between 15 and 37 degrees C studied, accompanied by a small negative entropy change, making enthalpy the main driving force of the interaction. The presence of cholesterol in the vesicles increased the binding affinity and the alpha-helix content of apoA-I but lowered the number of apoA-I bound per vesicle and the enthalpy and entropy changes per bound apoA-I. Binding affinity and stoichiometry were essentially invariant of temperature for binding to SUVs of POPC/FC at a molar ratio of 6/1 at (2.8-4) x 10(6) M(-1) and 2.4 apoA-I molecules bound per vesicle or 1.4 x 10(2) phospholipids per bound apoA-I. A plot of DeltaH degrees against temperature displayed a linear behavior, from which the DeltaC(p) degrees per mole of bound apoA-I was calculated to be -2.73 kcal/(mol x K). These results suggested that binding of apoA-I to POPC vesicles is characterized by nonclassical hydrophobic interactions, with alpha-helix formation as the main driving force for the binding to cholesterol-containing vesicles. In addition, comparison to literature data on peptides suggested a cooperativity of the helices in apoA-I in lipid interaction.

  5. Interaction of human apolipoprotein A-I with model membranes exhibiting lipid domains.

    PubMed

    Arnulphi, Cristina; Sánchez, Susana A; Tricerri, M Alejandra; Gratton, Enrico; Jonas, Ana

    2005-07-01

    Several mechanisms for cell cholesterol efflux have been proposed, including membrane microsolubilization, suggesting that the existence of specific domains could enhance the transfer of lipids to apolipoproteins. In this work isothermal titration calorimetry, circular dichroism spectroscopy, and two-photon microscopy are used to study the interaction of lipid-free apolipoprotein A-I (apoA-I) with small unilamellar vesicles (SUVs) of 1-palmitoyl, 2-oleoyl phosphatidylcholine (POPC) and sphingomyelin (SM), with and without cholesterol. Below 30 degrees C the calorimetric results show that apoA-I interaction with POPC/SM SUVs produces an exothermic reaction, characterized as nonclassical hydrophobic binding. The heat capacity change (DeltaCp degrees ) is small and positive, whereas it was larger and negative for pure POPC bilayers, in the absence of SM. Inclusion of cholesterol in the membranes induces changes in the observed thermodynamic pattern of binding and counteracts the formation of alpha-helices in the protein. Above 30 degrees C the reactions are endothermic. Giant unilamellar vesicles (GUVs) of identical composition to the SUVs, and two-photon fluorescence microscopy techniques, were utilized to further characterize the interaction. Fluorescence imaging of the GUVs indicates coexistence of lipid domains under 30 degrees C. Binding experiments and Laurdan generalized-polarization measurements suggest that there is no preferential binding of the labeled apoA-I to any particular domain. Changes in the content of alpha-helix, binding, and fluidity data are discussed in the framework of the thermodynamic parameters.

  6. Peptide-induced Asymmetric Distribution of Charged Lipids in a Vesicle Bilayer Revealed by Small-Angle Neutron Scattering

    NASA Astrophysics Data System (ADS)

    Heller, William; Qian, Shuo

    2012-02-01

    Cellular membranes are complex mixtures of lipids, proteins and other small molecules that provide functional, dynamic barriers between the cell and its environment, as well as between environments within the cell. The lipid composition of the membrane is highly specific and controlled in terms of both content and lipid localization. Here, small-angle neutron scattering and selective deuterium labeling were used to probe the impact of the membrane-active peptides melittin and alamethicin on the structure of lipid bilayers composed of a mixture of the lipids dimyristoyl phosphatidylglycerol (DMPG) and chain-perdeuterated dimyristoyl phosphatidylcholine (DMPC). We found that both peptides enriched the outer leaflet of the bilayer with the negatively charged DMPG, creating an asymmetric distribution of lipids. The level of enrichment is peptide concentration-dependent and is stronger for melittin than alamethicin. The enrichment between the inner and outer bilayer leaflets occurs at very low peptide concentrations, and increases with peptide concentration, including when the peptide adopts a membrane-spanning, pore-forming state.

  7. Novel pathways of apolipoprotein A-I metabolism in HDL of different sizes in humans

    PubMed Central

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

    2015-01-01

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

  8. Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apolipoprotein A-I transgenic mice.

    PubMed Central

    Berthou, L; Duverger, N; Emmanuel, F; Langouët, S; Auwerx, J; Guillouzo, A; Fruchart, J C; Rubin, E; Denèfle, P; Staels, B; Branellec, D

    1996-01-01

    The regulation of liver apolipoprotein (apo) A-I gene expression by fibrates was studied in human apo A-I transgenic mice containing a human genomic DNA fragment driving apo A-I expression in liver. Treatment with fenofibrate (0.5% wt/wt) for 7 d increased plasma human apo A-I levels up to 750% and HDL-cholesterol levels up to 200% with a shift to larger particles. The increase in human apo A-I plasma levels was time and dose dependent and was already evident after 3 d at the highest dose (0.5% wt/wt) of fenofibrate. In contrast, plasma mouse apo A-I concentration was decreased after fenofibrate in nontransgenic mice. The increase in plasma human apo A-I levels after fenofibrate treatment was associated with a 97% increase in hepatic human apo A-I mRNA, whereas mouse apo A-I mRNA levels decreased to 51%. In nontransgenic mice, a similar down-regulation of hepatic apo A-I mRNA levels was observed. Nuclear run-on experiments demonstrated that the increase in human apo A-I and the decrease in mouse apo A-I gene expression after fenofibrate occurred at the transcriptional level. Since part of the effects of fibrates are mediated through the nuclear receptor PPAR (peroxisome proliferator-activated receptor), the expression of the acyl CoA oxidase (ACO) gene was measured as a control of PPAR activation. Both in transgenic and nontransgenic mice, fenofibrate induced ACO mRNA levels up to sixfold. When transgenic mice were treated with gemfibrozil (0.5% wt/wt) plasma human apo A-I and HDL-cholesterol levels increased 32 and 73%, respectively, above control levels. The weaker effect of this compound on human apo A-I and HDL-cholesterol levels correlated with a less pronounced impact on ACO mRNA levels (a threefold increase) suggesting that the level of induction of human apo A-I gene is related to the PPAR activating potency of the fibrate used. Treatment of human primary hepatocytes with fenofibric acid (500 microM) provoked an 83 and 50% increase in apo A-I secretion and

  9. 12 CFR Appendixes A-I to Part 171 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 1 2013-01-01 2013-01-01 false A Appendixes A-I to Part 171 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY FAIR CREDIT REPORTING Appendixes A-I to Part 171 ...

  10. 12 CFR Appendixes A-I to Part 171 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 1 2012-01-01 2012-01-01 false A Appendixes A-I to Part 171 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY FAIR CREDIT REPORTING Appendixes A-I to Part 171 ...

  11. 12 CFR Appendixes A-I to Part 171 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 1 2014-01-01 2014-01-01 false A Appendixes A-I to Part 171 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY FAIR CREDIT REPORTING Appendixes A-I to Part 171 ...

  12. Small Wonders

    NASA Image and Video Library

    2017-06-28

    This montage of views from NASA's Cassini spacecraft shows three of Saturn's small ring moons: Atlas, Daphnis and Pan at the same scale for ease of comparison. Two differences between Atlas and Pan are obvious in this montage. Pan's equatorial band is much thinner and more sharply defined, and the central mass of Atlas (the part underneath the smooth equatorial band) appears to be smaller than that of Pan. Images of Atlas and Pan taken using infrared, green and ultraviolet spectral filters were combined to create enhanced-color views, which highlight subtle color differences across the moons' surfaces at wavelengths not visible to human eyes. (The Daphnis image was colored using the same green filter image for all three color channels, adjusted to have a realistic appearance next to the other two moons.) All of these images were taken using the Cassini spacecraft narrow-angle camera. The images of Atlas were acquired on April 12, 2017, at a distance of 10,000 miles (16,000 kilometers) and at a sun-moon-spacecraft angle (or phase angle) of 37 degrees. The images of Pan were taken on March 7, 2017, at a distance of 16,000 miles (26,000 kilometers) and a phase angle of 21 degrees. The Daphnis image was obtained on Jan. 16, 2017, at a distance of 17,000 miles (28,000 kilometers) and at a phase angle of 71 degrees. All images are oriented so that north is up. A monochrome version is available at https://photojournal.jpl.nasa.gov/catalog/PIA21449

  13. Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia.

    PubMed Central

    Ng, D S; Leiter, L A; Vezina, C; Connelly, P W; Hegele, R A

    1994-01-01

    We report a Canadian kindred with a novel mutation in the apolipoprotein (apo) A-I gene causing analphalipoproteinemia. The 34-yr-old proband, product of a consanguineous marriage, had bilateral retinopathy, bilateral cataracts, spinocerebellar ataxia, and tendon xanthomata. High density lipoprotein cholesterol (HDL-C) was < 0.1 mM and apoA-I was undetectable. Genomic DNA sequencing of the proband's apoA-I gene identified a nonsense mutation at codon [-2], which we designate as Q[-2]X. This mutation causes a loss of endonuclease digestion sites for both BbvI and Fnu4HI. Genotyping identified four additional homozygotes, four heterozygotes, and two unaffected subjects among the first-degree relatives. Q[-2]X homozygosity causes a selective failure to produce any portion of mature apoA-I, resulting in very low plasma level of HDL. Heterozygosity results in approximately half-normal apoA-I and HDL. Gradient gel electrophoresis and differential electroimmunodiffusion assay revealed that the HDL particles of the homozygotes had peak Stokes diameter of 7.9 nm and contained apoA-II without apoA-I (Lp-AII). Heterozygotes had an additional fraction of HDL3-like particles. Two of the proband's affected sisters had documented premature coronary heart disease. This kindred, the third reported apoA-I gene mutation causing isolated complete apoA-I deficiency, appears to be at significantly increased risk for atherosclerosis. Images PMID:8282791

  14. High-Density Lipoprotein Biogenesis: Defining the Domains Involved in Human Apolipoprotein A-I Lipidation.

    PubMed

    Pollard, Ricquita D; Fulp, Brian; Sorci-Thomas, Mary G; Thomas, Michael J

    2016-09-06

    The first step in removing cholesterol from a cell is the ATP-binding cassette transporter 1 (ABCA1)-driven transfer of cholesterol to lipid-free or lipid-poor apolipoprotein A-I (apoA-I), which yields cholesterol-rich nascent high-density lipoprotein (nHDL) that then matures in plasma to spherical, cholesteryl ester-rich HDL. However, lipid-free apoA-I has a three-dimensional (3D) conformation that is significantly different from that of lipidated apoA-I on nHDL. By comparing the lipid-free apoA-I 3D conformation of apoA-I to that of 9-14 nm diameter nHDL, we formulated the hypothetical helical domain transitions that might drive particle formation. To test the hypothesis, ten apoA-I mutants were prepared that contained two strategically placed cysteines several of which could form intramolecular disulfide bonds and others that could not form these bonds. Mass spectrometry was used to identify amino acid sequence and intramolecular disulfide bond formation. Recombinant HDL (rHDL) formation was assessed with this group of apoA-I mutants. ABCA1-driven nHDL formation was measured in four mutants and wild-type apoA-I. The mutants contained cysteine substitutions in one of three regions: the N-terminus, amino acids 34 and 55 (E34C to S55C), central domain amino acids 104 and 162 (F104C to H162C), and the C-terminus, amino acids 200 and 233 (L200C to L233C). Mutants were studied in the locked form, with an intramolecular disulfide bond present, or unlocked form, with the cysteine thiol blocked by alkylation. Only small amounts of rHDL or nHDL were formed upon locking the central domain. We conclude that both the N- and C-terminal ends assist in the initial steps in lipid acquisition, but that opening of the central domain was essential for particle formation.

  15. Interaction of Human Apolipoprotein A-I with Model Membranes Exhibiting Lipid Domains

    PubMed Central

    Arnulphi, Cristina; Sánchez, Susana A.; Tricerri, M. Alejandra; Gratton, Enrico; Jonas, Ana

    2005-01-01

    Several mechanisms for cell cholesterol efflux have been proposed, including membrane microsolubilization, suggesting that the existence of specific domains could enhance the transfer of lipids to apolipoproteins. In this work isothermal titration calorimetry, circular dichroism spectroscopy, and two-photon microscopy are used to study the interaction of lipid-free apolipoprotein A-I (apoA-I) with small unilamellar vesicles (SUVs) of 1-palmitoyl, 2-oleoyl phosphatidylcholine (POPC) and sphingomyelin (SM), with and without cholesterol. Below 30°C the calorimetric results show that apoA-I interaction with POPC/SM SUVs produces an exothermic reaction, characterized as nonclassical hydrophobic binding. The heat capacity change (ΔCp°) is small and positive, whereas it was larger and negative for pure POPC bilayers, in the absence of SM. Inclusion of cholesterol in the membranes induces changes in the observed thermodynamic pattern of binding and counteracts the formation of α-helices in the protein. Above 30°C the reactions are endothermic. Giant unilamellar vesicles (GUVs) of identical composition to the SUVs, and two-photon fluorescence microscopy techniques, were utilized to further characterize the interaction. Fluorescence imaging of the GUVs indicates coexistence of lipid domains under 30°C. Binding experiments and Laurdan generalized-polarization measurements suggest that there is no preferential binding of the labeled apoA-I to any particular domain. Changes in the content of α-helix, binding, and fluidity data are discussed in the framework of the thermodynamic parameters. PMID:15849246

  16. Small intestinal ischemia and infarction

    MedlinePlus

    Intestinal necrosis; Ischemic bowel - small intestine; Dead bowel - small intestine; Dead gut - small intestine; Infarcted bowel - small intestine; Atherosclerosis - small intestine; Hardening of the arteries - small intestine

  17. Genome-wide screen for modulation of hepatic apolipoprotein A-I (ApoA-I) secretion.

    PubMed

    Miles, Rebecca R; Perry, William; Haas, Joseph V; Mosior, Marian K; N'Cho, Mathias; Wang, Jian W J; Yu, Peng; Calley, John; Yue, Yong; Carter, Quincy; Han, Bomie; Foxworthy, Patricia; Kowala, Mark C; Ryan, Timothy P; Solenberg, Patricia J; Michael, Laura F

    2013-03-01

    Control of plasma cholesterol levels is a major therapeutic strategy for management of coronary artery disease (CAD). Although reducing LDL cholesterol (LDL-c) levels decreases morbidity and mortality, this therapeutic intervention only translates into a 25-40% reduction in cardiovascular events. Epidemiological studies have shown that a high LDL-c level is not the only risk factor for CAD; low HDL cholesterol (HDL-c) is an independent risk factor for CAD. Apolipoprotein A-I (ApoA-I) is the major protein component of HDL-c that mediates reverse cholesterol transport from tissues to the liver for excretion. Therefore, increasing ApoA-I levels is an attractive strategy for HDL-c elevation. Using genome-wide siRNA screening, targets that regulate hepatocyte ApoA-I secretion were identified through transfection of 21,789 siRNAs into hepatocytes whereby cell supernatants were assayed for ApoA-I. Approximately 800 genes were identified and triaged using a convergence of information, including genetic associations with HDL-c levels, tissue-specific gene expression, druggability assessments, and pathway analysis. Fifty-nine genes were selected for reconfirmation; 40 genes were confirmed. Here we describe the siRNA screening strategy, assay implementation and validation, data triaging, and example genes of interest. The genes of interest include known and novel genes encoding secreted enzymes, proteases, G-protein-coupled receptors, metabolic enzymes, ion transporters, and proteins of unknown function. Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor manumycin A caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes. In total, this work underscores the power of functional genetic assessment to identify new therapeutic targets.

  18. Polyadenylation site prediction using PolyA-iEP method.

    PubMed

    Kavakiotis, Ioannis; Tzanis, George; Vlahavas, Ioannis

    2014-01-01

    This chapter presents a method called PolyA-iEP that has been developed for the prediction of polyadenylation sites. More precisely, PolyA-iEP is a method that recognizes mRNA 3'ends which contain polyadenylation sites. It is a modular system which consists of two main components. The first exploits the advantages of emerging patterns and the second is a distance-based scoring method. The outputs of the two components are finally combined by a classifier. The final results reach very high scores of sensitivity and specificity.

  19. A novel compound 4010B-30 upregulates apolipoprotein A-I gene expression through activation of PPARγ in HepG2 cells.

    PubMed

    Du, Yu; Wang, Li; Si, Shuyi; Yang, Yuan; Hong, Bin

    2015-04-01

    Apolipoprotein (Apo) A-I is the major lipoprotein content of HDL and upregulating endogenous ApoA-I expression has been proposed as a desirable approach to raise the functional HDL. In this study we investigated the effect of a novel small molecule 4010B-30 on transcriptional regulation of ApoA-I gene in HepG2 cells, and the influence on the level of ApoA-I expression and function. Then the mechanisms by which 4010B-30 regulated ApoA-I expression was further explored. In human hepatic HepG2 cells, 4010B-30 increased the mRNA level and the protein production of ApoA-I both in cell lysates and media. The 4010B-30-induced ApoA-I containing particles increased cholesterol efflux from RAW264.7 macrophages. 4010B-30 also upregulated ABCA1 expression confirmed by transcriptional activity assay and Western blot analysis in both HepG2 and RAW264.7 cells. Promoter luciferase assay was used to identify the 4010B-30-responsive region which is mapped to the proximal -277bp region of the ApoA-I promoter. Further study indicated that the regulation of 4010B-30 on ApoA-I transcription or protein expression in HepG2 cells was abrogated with the suppression of PPARγ by its small interfering RNA or a specific inhibitor, GW9662. These findings suggest that the novel small molecular upregulator 4010B-30 increases ApoA-I gene expression, thereby enhances its function of promoting cholesterol efflux, as well as ABCA1 expression in vitro, and activation of PPARγ is required for 4010B-30 to induce hepatic ApoA-I production. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Apolipoprotein A-I interactions with insulin secretion and production.

    PubMed

    Rye, Kerry-Anne; Barter, Philip J; Cochran, Blake J

    2016-02-01

    Human population studies have established that an elevated plasma high-density lipoprotein cholesterol (HDL-C) level is associated with a decreased risk of developing cardiovascular disease. In addition to having several potentially cardioprotective functions, HDLs and apolipoprotein (apo)A-I, the main HDL apolipoprotein, also have antidiabetic properties. Interventions that elevate plasma HDL-C and apoA-I levels improve glycemic control in people with type 2 diabetes mellitus by enhancing pancreatic β-cell function and increasing insulin sensitivity. This review is concerned with recent advances in understanding the mechanisms by which HDLs and apoA-I improve pancreatic β-cell function. HDLs and apoA-I increase insulin synthesis and secretion in pancreatic β cells. The underlying mechanism of this effect is similar to what has been reported for intestinally derived incretins, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, which both increase β-cell insulin secretion under high glucose conditions. This involves the activation of a heterotrimeric G protein Gαs subunit on the β-cell surface that leads to induction of a transmembrane adenylyl cyclase, increased intracellular cyclic adenosine monophosphate and Ca levels, and activation of protein kinase A. Protein kinase A increases insulin synthesis by excluding FoxO1 from the β-cell nucleus and derepressing transcription of the insulin gene.

  1. Try P.R.A.I.S.E.

    ERIC Educational Resources Information Center

    Wollam, Scott A.

    1979-01-01

    P.R.A.I.S.E. (Positive Reinforcement and Individualized Systematic Economics) is a multifaceted money system which utilizes positive and negative reinforcement and, at the same time, incorporates peer pressure and reinforcement for behavior modification. The system motivates, relates closely to life situations, and can be applied to all areas of…

  2. A novel approach to oral apoA-I mimetic therapy[S

    PubMed Central

    Chattopadhyay, Arnab; Navab, Mohamad; Hough, Greg; Gao, Feng; Meriwether, David; Grijalva, Victor; Springstead, James R.; Palgnachari, Mayakonda N.; Namiri-Kalantari, Ryan; Su, Feng; Van Lenten, Brian J.; Wagner, Alan C.; Anantharamaiah, G. M.; Farias-Eisner, Robin; Reddy, Srinivasa T.; Fogelman, Alan M.

    2013-01-01

    Transgenic tomato plants were constructed with an empty vector (EV) or a vector expressing an apoA-I mimetic peptide, 6F. EV or 6F tomatoes were harvested, lyophilized, ground into powder, added to Western diet (WD) at 2.2% by weight, and fed to LDL receptor-null (LDLR−/−) mice at 45 mg/kg/day 6F. After 13 weeks, the percent of the aorta with lesions was 4.1 ± 4%, 3.3 ± 2.4%, and 1.9 ± 1.4% for WD, WD + EV, and WD + 6F, respectively (WD + 6F vs. WD, P = 0.0134; WD + 6F vs. WD + EV, P = 0.0386; WD + EV vs. WD, not significant). While body weight did not differ, plasma serum amyloid A (SAA), total cholesterol, triglycerides, and lysophosphatidic acid (LPA) levels were less in WD + 6F mice; P < 0.0295. HDL cholesterol and paroxonase-1 activity (PON) were higher in WD + 6F mice (P = 0.0055 and P = 0.0254, respectively), but not in WD + EV mice. Plasma SAA, total cholesterol, triglycerides, LPA, and 15-hydroxyeicosatetraenoic acid (HETE) levels positively correlated with lesions (P < 0.0001); HDL cholesterol and PON were inversely correlated (P < 0.0001). After feeding WD + 6F: i) intact 6F was detected in small intestine (but not in plasma); ii) small intestine LPA was decreased compared with WD + EV (P < 0.0469); and iii) small intestine LPA 18:2 positively correlated with the percent of the aorta with lesions (P < 0.0179). These data suggest that 6F acts in the small intestine and provides a novel approach to oral apoA-I mimetic therapy. PMID:23378594

  3. Apolipoprotein A-I: A Molecule of Diverse Function.

    PubMed

    Mangaraj, Manaswini; Nanda, Rachita; Panda, Suchismita

    2016-07-01

    Apolipoprotein A-I (apo A-I) an indispensable component and a major structural protein of high-density lipoprotein (HDL), plays a vital role in reverse cholesterol transport and cellular cholesterol homeostasis since its identification. Its multifunctional role in immunity, inflammation, apoptosis, viral, bacterial infection etc. has crossed its boundary of its potential of protecting cardiovascular system and lowering cardiovascular disease risk, attributing HDL to be known as a protective fat removal particle. Its structural homology with prostacyclin stabilization factor has contributed to its anti-clotting and anti-aggregatory effect on platelet which has potentiated its cardio-protective role as well as its therapeutic efficacy against Alzheimer's disease. The binding affinity and neutralising action against endotoxin lipopolysaccharide, reduces the toxic manifestations of septic shock. As a negative acute phase protein, it blocks T-cell signalling of macrophages. However the recently identified anti-tumor activity of apo A-I has been highlighted in various models of melanoma, lung cancer, ovarian cancer, lymphoblastic leukaemia, gastric as well as pancreatic cancers. These cancer fighting effects are directed towards regression of tumor size and distant metastasis by its immuno modulatory activity as well as its clearing effect on serum lysophospholipids. This lowering effect on lysophospholipid concentration is utilized by apo A-I mimetic peptides to be used in retarding tumor cell proliferation and as a potential cancer therapeutic agent. Not only that, it inhibits the tumor associated neo-angiogenesis as well as brings down the matrix degrading enzymes associated with tumor metastasis. However this efficient therapeutic potential of apo A-I as an anti tumor agent awaits further future experimental studies in humans.

  4. The promise of apolipoprotein A-I mimetics.

    PubMed

    Mendez, Armando J

    2010-04-01

    Synthetic high-density lipoprotein (HDL) and apolipoprotein (apo) A-I mimetic peptides emulate many of the atheroprotective biological functions attributed to HDL and can modify atherosclerotic disease processes. Administration of these agents as HDL replacement or modifying therapy has tremendous potential of providing new treatments for cardiovascular disease. Progress in the understanding of these agents is discussed in this review. Prospective, observational, and interventional studies have convincingly demonstrated that elevated serum levels of high-density lipoprotein-cholesterol (HDL-C) are associated with reduced risk for coronary heart disease (CHD). Although traditional pharmacological agents have shown modest utility in raising HDL levels and reducing CHD risk, use of HDL and apo A-I mimetics provides novel therapies to not only increase HDL levels, but to also influence HDL functionality. Evidence developed over the last several years has identified a number of pathways affected by synthetic HDL and apoA-I mimetic peptides, including enhancing reverse cholesterol transport and reducing oxidation and inflammation that directly influence the progression and regression of atherosclerotic disease. Clinical trials of relatively short-term synthetic HDL infusion into patients with CHD demonstrate beneficial effects. Use of apo A-I mimetic peptides could potentially overcome some of the limitations associated with use of the intact apo. Studies to establish the most efficacious peptides, optimal dosing regimens, and routes of administration are needed. Use of apo A-I mimetic peptides shows great promise as a therapeutic modality for HDL replacement and enhancing HDL function in treatment of patients with CHD.

  5. Small bowel resection

    MedlinePlus

    Small intestine surgery; Bowel resection - small intestine; Resection of part of the small intestine; Enterectomy ... her hand inside your belly to feel the intestine or remove the diseased segment. Your belly is ...

  6. Small Intestine Cancer Treatment

    MedlinePlus

    ... Health Professional Small Intestine Cancer Treatment Research Small Intestine Cancer Treatment (PDQ®)–Patient Version General Information About Small Intestine Cancer Go to Health Professional Version Key Points ...

  7. Small Scale Organic Techniques

    ERIC Educational Resources Information Center

    Horak, V.; Crist, DeLanson R.

    1975-01-01

    Discusses the advantages of using small scale experimentation in the undergraduate organic chemistry laboratory. Describes small scale filtration techniques as an example of a semi-micro method applied to small quantities of material. (MLH)

  8. Lung cancer - small cell

    MedlinePlus

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  9. Small bowel bacterial overgrowth

    MedlinePlus

    Overgrowth - intestinal bacteria; Bacterial overgrowth - intestine; Small intestinal bacterial overgrowth; SIBO ... intestine does not have a high number of bacteria. Excess bacteria in the small intestine may use ...

  10. Human macrophage cathepsin B-mediated C-terminal cleavage of apolipoprotein A-I at Ser228 severely impairs antiatherogenic capacity.

    PubMed

    Dinnes, Donna Lee M; White, Melanie Y; Kockx, Maaike; Traini, Mathew; Hsieh, Victar; Kim, Mi-Jurng; Hou, Liming; Jessup, Wendy; Rye, Kerry-Anne; Thaysen-Andersen, Morten; Cordwell, Stuart J; Kritharides, Leonard

    2016-12-01

    Apolipoprotein A-I (apoA-I) is the major component of HDL and central to the ability of HDL to stimulate ATP-binding cassette transporter A1 (ABCA1)-dependent, antiatherogenic export of cholesterol from macrophage foam cells, a key player in the pathology of atherosclerosis. Cell-mediated modifications of apoA-I, such as chlorination, nitration, oxidation, and proteolysis, can impair its antiatherogenic function, although it is unknown whether macrophages themselves contribute to such modifications. To investigate this, human monocyte-derived macrophages (HMDMs) were incubated with human apoA-I under conditions used to induce cholesterol export. Two-dimensional gel electrophoresis and Western blot analysis identified that apoA-I is cleaved (∼20-80%) by HMDMs in a time-dependent manner, generating apoA-I of lower MW and isoelectric point. Mass spectrometry analysis identified a novel C-terminal cleavage site of apoA-I between Ser(228)-Phe(229) Recombinant apoA-I truncated at Ser(228) demonstrated profound loss of capacity to solubilize lipid and to promote ABCA1-dependent cholesterol efflux. Protease inhibitors, small interfering RNA knockdown in HMDMs, mass spectrometry analysis, and cathepsin B activity assays identified secreted cathepsin B as responsible for apoA-I cleavage at Ser(228) Importantly, C-terminal cleavage of apoA-I was also detected in human carotid plaque. Cleavage at Ser(228) is a novel, functionally important post-translational modification of apoA-I mediated by HMDMs that limits the antiatherogenic properties of apoA-I.-Dinnes, D. L. M., White, M. Y., Kockx, M., Traini, M., Hsieh, V., Kim, M.-J., Hou, L., Jessup, W., Rye, K.-A., Thaysen-Andersen, M., Cordwell, S. J., Kritharides, L. Human macrophage cathepsin B-mediated C-terminal cleavage of apolipoprotein A-I at Ser(228) severely impairs antiatherogenic capacity. © FASEB.

  11. Local Vascular Gene Therapy With Apolipoprotein A-I to Promote Regression of Atherosclerosis.

    PubMed

    Wacker, Bradley K; Dronadula, Nagadhara; Zhang, Jingwan; Dichek, David A

    2017-02-01

    Gene therapy, delivered directly to the blood vessel wall, could potentially prevent atherosclerotic lesion growth and promote atherosclerosis regression. Previously, we reported that a helper-dependent adenoviral (HDAd) vector expressing apolipoprotein A-I (apoA-I) in carotid endothelium of fat-fed rabbits reduced early (4 weeks) atherosclerotic lesion growth. Here, we tested whether the same HDAd-delivered to the existing carotid atherosclerotic lesions-could promote regression. Rabbits (n=26) were fed a high-fat diet for 7 months, then treated with bilateral carotid gene transfer. One carotid was infused with an HDAd expressing apoA-I (HDAdApoAI) and the other with a control nonexpressing HDAd (HDAdNull). The side with HDAdApoAI was randomized. Rabbits were then switched to regular chow, lowering their plasma cholesterols by over 70%. ApoA-I mRNA and protein were detected in HDAdApoAI-transduced arteries. After 7 weeks of gene therapy, compared with HDAdNull-treated arteries in the same rabbits, HDAdApoAI-treated arteries had significantly less vascular cell adhesion molecule-1 expression (28%; P=0.04) along with modest but statistically insignificant trends toward decreased intimal lesion volume, lipid and macrophage content, and intercellular adhesion molecule-1 expression (9%-21%; P=0.1-0.4). Post hoc subgroup analysis of rabbits with small-to-moderate-sized lesions (n=20) showed that HDAdApoAI caused large reductions in lesion volume, lipid content, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 expression (30%-50%; P≤0.04 for all). Macrophage content was reduced by 30% (P=0.06). There was a significant interaction (P=0.02) between lesion size and treatment efficacy. Even when administered on a background of aggressive lowering of plasma cholesterol, local HDAdApoAI vascular gene therapy may promote rapid regression of small-to-moderate-sized atherosclerotic lesions. © 2016 American Heart Association, Inc.

  12. Novel Pathways of Apolipoprotein A-I Metabolism in High-Density Lipoprotein of Different Sizes in Humans.

    PubMed

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

    2016-01-01

    A prevailing concept is that high-density lipoprotein (HDL) is secreted into the systemic circulation as a small mainly discoidal particle, which expands progressively and becomes spherical by uptake and esterification of cellular cholesterol and then contracts by cholesterol ester delivery to the liver, a process known as reverse cholesterol transport, thought to be impaired in people with low HDL cholesterol (HDLc). This metabolic framework has not been established in humans. We studied the metabolism of apolipoprotein A-I in 4 standard HDL sizes by endogenous isotopic labeling in 6 overweight adults with low HDLc and in 6 adults with normal body weight with high plasma HDLc. Contrary to expectation, HDL was secreted into the circulation in its entire size distribution from very small to very large similarly in both groups. Very small (prebeta) HDL comprised only 8% of total apolipoprotein A-I secretion. Each HDL subfraction circulated mostly within its secreted size range for 1 to 4 days and then was cleared. Enlargement of very small and medium to large and very large HDL and generation of very small from medium HDL were minor metabolic pathways. Prebeta HDL was cleared slower, whereas medium, large, and very large HDL were cleared faster in the low HDLc group. A new model is proposed from these results in which HDL is metabolized in plasma mainly within several discrete, stable sizes across the common range of HDLc concentrations. © 2015 American Heart Association, Inc.

  13. Mycoplasma gallisepticum (HS strain) surface lipoprotein pMGA interacts with host apolipoprotein A-I during infection in chicken.

    PubMed

    Hu, Fuli; Zhao, Chengcheng; Bi, Dingren; Tian, Wei; Chen, Jiao; Sun, Jianjun; Peng, Xiuli

    2016-02-01

    The adhesin protein from Mycoplasma gallisepticum (HS strain), namely pMGA1.2, is required for M. gallisepticum (MG) infection in chicken. However, the host factor(s) that interact with pMGA1.2 is not known. In this study, we prepared the membrane fraction of trachea epithelial cells from chicken embryos. Using an improved virus overlay protein blot assay (VOPBA) and glutathione S-transferase (GST) pull-down assay, we found that pMGA1.2 specifically bound to a ∼30 kDa host protein. This host protein was further identified by mass spectrometry as chicken apolipoprotein A-I (ApoA-I). We expressed and purified the recombinant ApoA-I protein in Escherichia coli and confirmed that it bound to the purified pMGA1.2 protein in vitro. Transiently expressed pMGA1.2 and ApoA-I were colocalized in HeLa cells. Finally, we designed small interfering RNA (siRNA) molecules to knock down the expression of either ApoA-I or pMGA1.2, which inhibited the MG-induced cell cycle disruption in cells of chicken embryo fibroblast cell line (DF-1). Similarly, knockdown of ApoA-I inhibited the cilia loss and damage in chicken trachea cells in MG infection. In summary, ApoA-I may be an essential host factor in MG infection through interacting with pMGA1.2.

  14. Natural human apoA-I mutations L141RPisa and L159RFIN alter HDL structure and functionality and promote atherosclerosis development in mice.

    PubMed

    Tiniakou, Ioanna; Kanaki, Zoi; Georgopoulos, Spiros; Chroni, Angeliki; Van Eck, Miranda; Fotakis, Panagiotis; Zannis, Vassilis I; Kardassis, Dimitris

    2015-11-01

    Mutations in human apolipoprotein A-I (apoA-I) are associated with low high-density lipoprotein (HDL) cholesterol levels and pathological conditions such as premature atherosclerosis and amyloidosis. In this study we functionally characterized two natural human apoA-I mutations, L141RPisa and L159RFIN, in vivo. We generated transgenic mice expressing either wild-type (WT) or the two mutant forms of human apoA-I on a mouse apoA-I(-/-) background and analyzed for abnormalities in their lipid and lipoprotein profiles. HDL structure and functionality, as well as atherosclerosis development following a 14-week high-fat diet were assessed in these mice. The expression of either apoA-I mutant was associated with markedly reduced serum apoA-I (<10% of WT apoA-I), total and HDL-cholesterol levels (∼20% and ∼7% of WT apoA-I, respectively) and the formation of few small size HDL particles with preβ2 and α3, α4 electrophoretic mobility. HDL particles containing either of the two apoA-I mutants exhibited attenuated anti-oxidative properties as indicated by their inability to prevent low-density lipoprotein oxidation, and by decreased activities of paraoxonase-1 and platelet-activating factor acetylhydrolase. However, the apoA-I(L141R)Pisa or apoA-I(L159R)FIN-containing HDL particles demonstrated increased capacity to promote ATP-Binding Cassette Transporter A1-mediated cholesterol efflux from macrophages. Expression of apoA-I(L141R)Pisa or apoA-I(L159R)FIN mutations in mice was associated with increased diet-induced atherosclerosis compared to either WT apoA-I transgenic or apoA-I(-/-) mice. These findings suggest that natural apoA-I mutations L141RPisa and L159RFIN affect the biogenesis and the functionality of HDL in vivo and predispose to diet-induced atherosclerosis in the absence of any other genetic defect. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. ABCA1 (ATP-Binding Cassette Transporter A1) Mediates ApoA-I (Apolipoprotein A-I) and ApoA-I Mimetic Peptide Mobilization of Extracellular Cholesterol Microdomains Deposited by Macrophages.

    PubMed

    Jin, Xueting; Sviridov, Denis; Liu, Ying; Vaisman, Boris; Addadi, Lia; Remaley, Alan T; Kruth, Howard S

    2016-12-01

    We examined the function of ABCA1 (ATP-binding cassette transporter A1) in ApoA-I (apolipoprotein A-I) mobilization of cholesterol microdomains deposited into the extracellular matrix by cholesterol-enriched macrophages. We have also determined whether an ApoA-I mimetic peptide without and with complexing to sphingomyelin can mobilize macrophage-deposited cholesterol microdomains. Extracellular cholesterol microdomains deposited by cholesterol-enriched macrophages were detected with a monoclonal antibody, 58B1. ApoA-I and an ApoA-I mimetic peptide 5A mobilized cholesterol microdomains deposited by ABCA1(+/+) macrophages but not by ABCA1(-/-) macrophages. In contrast, ApoA-I mimetic peptide 5A complexed with sphingomyelin could mobilize cholesterol microdomains deposited by ABCA1(-/-) macrophages. Our findings show that a unique pool of extracellular cholesterol microdomains deposited by macrophages can be mobilized by both ApoA-I and an ApoA-I mimetic peptide but that mobilization depends on macrophage ABCA1. It is known that ABCA1 complexes ApoA-I and ApoA-I mimetic peptide with phospholipid, a cholesterol-solubilizing agent, explaining the requirement for ABCA1 in extracellular cholesterol microdomain mobilization. Importantly, ApoA-I mimetic peptide already complexed with phospholipid can mobilize macrophage-deposited extracellular cholesterol microdomains even in the absence of ABCA1. © 2016 American Heart Association, Inc.

  16. Small bowel resection - discharge

    MedlinePlus

    ... chap 26. Read More Colon cancer Crohn disease Intestinal obstruction Small bowel resection Patient Instructions Bland diet Crohn ... Editorial team. Related MedlinePlus Health Topics Intestinal Cancer Intestinal Obstruction Small Intestine Disorders Browse the Encyclopedia A.D. ...

  17. Small Intestine Disorders

    MedlinePlus

    Your small intestine is the longest part of your digestive system - about twenty feet long! It connects your stomach to ... many times to fit inside your abdomen. Your small intestine does most of the digesting of the foods ...

  18. Small intestine (image)

    MedlinePlus

    The small intestine is the portion of the digestive system most responsible for absorption of nutrients from food into the ... the duodenum. This short first portion of the small intestine is followed by the jejunum and the ileum. ...

  19. Small Libraries, Big Technology

    ERIC Educational Resources Information Center

    Roberts,Gary

    2005-01-01

    Small libraries don't have the resources to adopt every new technology. It is important that small libraries operate strategically, adopting only those technologies that are the most beneficial to their patrons.

  20. Small Business Pedagogic Practices

    ERIC Educational Resources Information Center

    Billett, Stephen; Hernon-Tinning, Barnie; Ehrich, Lisa

    2003-01-01

    Understanding how learning for small businesses should best proceed constitutes a worthwhile, yet challenging, pedagogic project. In order to maintain their viability, small businesses need to be able to respond to new practices and tasks. Yet small businesses seem neither attracted to nor to value the kinds of taught courses that are the standard…

  1. Small Business Pedagogic Practices

    ERIC Educational Resources Information Center

    Billett, Stephen; Hernon-Tinning, Barnie; Ehrich, Lisa

    2003-01-01

    Understanding how learning for small businesses should best proceed constitutes a worthwhile, yet challenging, pedagogic project. In order to maintain their viability, small businesses need to be able to respond to new practices and tasks. Yet small businesses seem neither attracted to nor to value the kinds of taught courses that are the standard…

  2. Small Colleges, Big Missions.

    ERIC Educational Resources Information Center

    Griffin, W. A., Jr., Ed.

    This monograph by the members of the American Association of Community Colleges' Commission on Small and/or Rural Community Colleges shares small and rural community college experiences. In "Leaders through Community Service," Jacqueline D. Taylor provides a model for how small and rural community colleges can be involved in building leaders…

  3. Chairing a Small Department.

    ERIC Educational Resources Information Center

    Bowker, Lee H.; Lynch, David M.

    Ten management problems for chairs of small departments in small colleges are discussed, along with problem-solving strategies for these administrators. Serious disagreements within a small and intimate department may create a country club culture in which differences are smoothed over and the personal idiosyncrasies of individual members are…

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

    PubMed

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

    2017-09-15

    Although women have higher HDL-C than men, their HDL particles are also prone to become small, dense and dysfunctional in case of T2DM. To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL-C to its main apolipoprotein (apoA-I), as [HDL-C/apoA-I]. This ratio estimates HDLs size and provides indices as to their number, cholesterol load, and density. We stratified 280 Caucasian T2DM women according to [HDL-C/apoA-I] quartiles (Q), to determine how it segregates cardiometabolic risk, β-cell function, glycemic control, and vascular complications. Five parameters were derived from combined determination of HDL-C and apoA-I : HDL size; HDL number; cholesterol load per particle (pP); apoA-IpP; and HDL density. An adverse cardiometabolic profile characterized Q-I and Q-II patients, whose HDLs were denser and apoA-I-depleted, whereas Q-III patients had HDLs with characteristics closer to controls. Q-IV patients had HDLs of supernormal size/composition and a more favorable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, β-cell function (32% vs 23%); exogenous insulin (44 vs 89 U/day), and glycemic control (HbA1c: 56 vs 61 mmol/mol), associated with lower prevalence of micro-/macrovascular complications: all-cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all-cause macroangiopathy 19% vs 31%; and CAD: 6% vs 24% (p<0.05). [HDL-C/apoA-I] can stratify T2DM women according to metabolic phenotype, macrovascular and coronary damage, β-cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women. This article is protected by copyright. All rights reserved.

  5. 22 CFR 214.13 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Responsibilities within A.I.D. 214.13 Section... Establishment of Advisory Committees § 214.13 Responsibilities within A.I.D. (a) The A.I.D. Office or Bureau seeking establishment of a new A.I.D. advisory committee: (1) Justifies the need for the advisory...

  6. 22 CFR 214.13 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Responsibilities within A.I.D. 214.13 Section... Establishment of Advisory Committees § 214.13 Responsibilities within A.I.D. (a) The A.I.D. Office or Bureau seeking establishment of a new A.I.D. advisory committee: (1) Justifies the need for the advisory...

  7. 22 CFR 214.13 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Responsibilities within A.I.D. 214.13 Section... Establishment of Advisory Committees § 214.13 Responsibilities within A.I.D. (a) The A.I.D. Office or Bureau seeking establishment of a new A.I.D. advisory committee: (1) Justifies the need for the advisory...

  8. 22 CFR 214.13 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Responsibilities within A.I.D. 214.13 Section... Establishment of Advisory Committees § 214.13 Responsibilities within A.I.D. (a) The A.I.D. Office or Bureau seeking establishment of a new A.I.D. advisory committee: (1) Justifies the need for the advisory...

  9. 22 CFR 214.13 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Responsibilities within A.I.D. 214.13 Section... Establishment of Advisory Committees § 214.13 Responsibilities within A.I.D. (a) The A.I.D. Office or Bureau seeking establishment of a new A.I.D. advisory committee: (1) Justifies the need for the advisory...

  10. 22 CFR 214.31 - A.I.D. Advisory Committee Representative.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false A.I.D. Advisory Committee Representative. 214... MANAGEMENT Operation of Advisory Committees § 214.31 A.I.D. Advisory Committee Representative. (a) For each advisory committee used by A.I.D., the Administrator designates an A.I.D., employee to serve as the A.I.D...

  11. 22 CFR 214.31 - A.I.D. Advisory Committee Representative.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false A.I.D. Advisory Committee Representative. 214... MANAGEMENT Operation of Advisory Committees § 214.31 A.I.D. Advisory Committee Representative. (a) For each advisory committee used by A.I.D., the Administrator designates an A.I.D., employee to serve as the A.I.D...

  12. Small Business Procurement Event

    DTIC Science & Technology

    2014-08-13

    Small Business Procurement Event 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK...distribution unlimited 13. SUPPLEMENTARY NOTES NDIA 27th Navy Gold Coast Small Business Procurement Event , 12-13 Aug 2014, San Diego, CA. 14. ABSTRACT...18 Target the Small Business Accessible Market within the Department of the Navy $77.8B Department of the Navy Total SB Eligible Spend

  13. Small Wastewater Systems Research

    EPA Pesticide Factsheets

    Small communities face barriers to building and maintaining effective wastewater treatment services, challenges include financial/economic limitations, lack of managerial training and geographic isolation/remoteness.

  14. Small Animal Care.

    ERIC Educational Resources Information Center

    Livesey, Dennis W.; Fong, Stephen

    This small animal care course guide is designed for students who will be seeking employment in veterinary hospitals, kennels, grooming shops, pet shops, and small-animal laboratories. The guide begins with an introductory section that gives the educational philosophy of the course, job categories and opportunities, units of instruction required…

  15. Small Animal Care.

    ERIC Educational Resources Information Center

    Livesey, Dennis W.; Fong, Stephen

    This small animal care course guide is designed for students who will be seeking employment in veterinary hospitals, kennels, grooming shops, pet shops, and small-animal laboratories. The guide begins with an introductory section that gives the educational philosophy of the course, job categories and opportunities, units of instruction required…

  16. Industrial Education. "Small Engines".

    ERIC Educational Resources Information Center

    Parma City School District, OH.

    Part of a series of curriculum guides dealing with industrial education in junior high schools, this guide provides the student with information and manipulative experiences on small gasoline engines. Included are sections on shop adjustment, safety, small engines, internal combustion, engine construction, four stroke engines, two stroke engines,…

  17. Sensitive Small Area Photometer

    ERIC Educational Resources Information Center

    Levenson, M. D.

    1970-01-01

    Describes a simple photometer capable of measuring small light intensities over small areas. The inexpensive, easy-to- construct instrument is intended for use in a student laboratory to measure the light intensities in a diffraction experiment from single or multiple slits. Typical experimental results are presented along with the theoretical…

  18. Industrial Education. "Small Engines".

    ERIC Educational Resources Information Center

    Parma City School District, OH.

    Part of a series of curriculum guides dealing with industrial education in junior high schools, this guide provides the student with information and manipulative experiences on small gasoline engines. Included are sections on shop adjustment, safety, small engines, internal combustion, engine construction, four stroke engines, two stroke engines,…

  19. IBM Small Business Survey.

    ERIC Educational Resources Information Center

    International Business Machines Corp., Armonk, NY.

    A telephone survey conducted March 15-22, 1991, examined how small businesses are currently performing. Interviewees were 400 small business owners randomly selected from a Dun and Bradstreet list of companies with 50 or fewer employees. Major findings were as follows: (1) owners were survivors, highly confident in their own abilities, and…

  20. Veterans in Small Business.

    ERIC Educational Resources Information Center

    American Association of Community and Junior Colleges, Washington, DC. National Small Business Training Network.

    These materials provide information on conducting small business training seminars for veterans. First, a discussion is presented of the development of the guide based on 1983 field testing of the seminar and evaluations conducted by Small Business Administration (SBA) officials, the seminar contracts, and trainers. The next sections deal with the…

  1. Big Project, Small Leaders

    ERIC Educational Resources Information Center

    Schon, Jennifer A.; Eitel, Karla B.; Bingaman, Deirdre; Miller, Brant G.; Rittenburg, Rebecca A.

    2014-01-01

    Donnelly, Idaho, is a small town surrounded by private ranches and Forest Service property. Through the center of Donnelly runs Boulder Creek, a small tributary feeding into Cascade Lake Reservoir. Boulder Creek originates from a mountain lake north of Donnelly. Since 1994 it has been listed as "impaired" by the Environmental Protection…

  2. Small Wind Information (Postcard)

    SciTech Connect

    Not Available

    2011-08-01

    The U.S. Department of Energy's Wind Powering America initiative maintains a website section devoted to information about small wind turbines for homeowners, ranchers, and small businesses. This postcard is a marketing piece that stakeholders can provide to interested parties; it will guide them to this online resource.

  3. Small Mammal Intrigue.

    ERIC Educational Resources Information Center

    Cristol, Daniel A.

    1985-01-01

    Gives introductory information about the study of small mammals including the selection and use of harmless live-traps, handling and identification, techniques for observation and trapping in the wild, and safety measures. Suggests useful references for teachers wishing to develop a small mammal study program for their students. (JHZ)

  4. Small Schools, Big Future

    ERIC Educational Resources Information Center

    Halsey, R. John

    2011-01-01

    Historically, small schools have played a very important role in the provision of schooling in Australia. Numerically, using an enrollment of 200 or less, small schools represent approximately 45% of the schools in Australia. Population growth and the consequences of this, in particular for food production, water and energy, mean that the…

  5. Big Project, Small Leaders

    ERIC Educational Resources Information Center

    Schon, Jennifer A.; Eitel, Karla B.; Bingaman, Deirdre; Miller, Brant G.; Rittenburg, Rebecca A.

    2014-01-01

    Donnelly, Idaho, is a small town surrounded by private ranches and Forest Service property. Through the center of Donnelly runs Boulder Creek, a small tributary feeding into Cascade Lake Reservoir. Boulder Creek originates from a mountain lake north of Donnelly. Since 1994 it has been listed as "impaired" by the Environmental Protection…

  6. Small Schools, Big Future

    ERIC Educational Resources Information Center

    Halsey, R. John

    2011-01-01

    Historically, small schools have played a very important role in the provision of schooling in Australia. Numerically, using an enrollment of 200 or less, small schools represent approximately 45% of the schools in Australia. Population growth and the consequences of this, in particular for food production, water and energy, mean that the…

  7. Small Groups in Action

    ERIC Educational Resources Information Center

    Suessmuth, Patrick

    1974-01-01

    Small groups can sometimes be difficult to set up and work with properly. A number of tips for small group instruction are divided into seven areas: (1) presenting tasks; (2) group seating; (3) task time; (4) answering questions; (5) teacher's role in observing groups; (6) group noise level patterns; and (7) serial take-ups. (BP)

  8. Small Soil Animals.

    ERIC Educational Resources Information Center

    Seevers, Elmer R.

    1978-01-01

    Describes an inexpensive technique for providing student opportunities to observe and identify the variety of small animals living in the first few inches below the surface of the soil. A classification key to some small soil animals is also presented. (HM)

  9. Small and Young

    NASA Image and Video Library

    2015-03-20

    Small graben, narrow linear troughs, have been found associated with small scarps (bottom left, white arrows) on Mercury and the Moon. These graben (bottom right, white arrows) likely resulted from the bending and extension of the upper crust in response to scarp formation (bottom illustration) and are only tens of meters wide. On the basis of the rate of degradation and infilling of small troughs on the Moon by continuous meteoroid bombardment, small lunar graben and their associated scarps are less than 50 Myr old! It is likely that Mercury's small graben and their associated scarps are younger still, because the cratering rate on Mercury is greater than on the Moon. http://photojournal.jpl.nasa.gov/catalog/PIA19254

  10. Small GTPases and cilia.

    PubMed

    Li, Yujie; Hu, Jinghua

    2011-01-01

    Small GTPases are key molecular switches that bind and hydrolyze GTP in diverse membrane- and cytoskeleton-related cellular processes. Recently, mounting evidences have highlighted the role of various small GTPases, including the members in Arf/Arl, Rab, and Ran subfamilies, in cilia formation and function. Once overlooked as an evolutionary vestige, the primary cilium has attracted more and more attention in last decade because of its role in sensing various extracellular signals and the association between cilia dysfunction and a wide spectrum of human diseases, now called ciliopathies. Here we review recent advances about the function of small GTPases in the context of cilia, and the correlation between the functional impairment of small GTPases and ciliopathies. Understanding of these cellular processes is of fundamental importance for broadening our view of cilia development and function in normal and pathological states and for providing valuable insights into the role of various small GTPases in disease processes, and their potential as therapeutic targets.

  11. Technology for small spacecraft

    NASA Astrophysics Data System (ADS)

    This report gives the results of a study by the National Research Council's Panel on Small Spacecraft Technology that reviewed NASA's technology development program for small spacecraft and assessed technology within the U.S. government and industry that is applicable to small spacecraft. The panel found that there is a considerable body of advanced technology currently available for application by NASA and the small spacecraft industry that could provide substantial improvement in capability and cost over those technologies used for current NASA small spacecraft. These technologies are the result of developments by commercial companies, Department of Defense agencies, and to a lesser degree NASA. The panel also found that additional technologies are being developed by these same entities that could provide additional substantial improvement if development is successfully completed. Recommendations for future technology development efforts by NASA across a broad technological spectrum are made.

  12. Technology for small spacecraft

    NASA Technical Reports Server (NTRS)

    1994-01-01

    This report gives the results of a study by the National Research Council's Panel on Small Spacecraft Technology that reviewed NASA's technology development program for small spacecraft and assessed technology within the U.S. government and industry that is applicable to small spacecraft. The panel found that there is a considerable body of advanced technology currently available for application by NASA and the small spacecraft industry that could provide substantial improvement in capability and cost over those technologies used for current NASA small spacecraft. These technologies are the result of developments by commercial companies, Department of Defense agencies, and to a lesser degree NASA. The panel also found that additional technologies are being developed by these same entities that could provide additional substantial improvement if development is successfully completed. Recommendations for future technology development efforts by NASA across a broad technological spectrum are made.

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

    PubMed Central

    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

  14. PPARγ Represses Apolipoprotein A-I Gene but Impedes TNFα-Mediated ApoA-I Downregulation in HepG2 Cells.

    PubMed

    Shavva, Vladimir S; Mogilenko, Denis A; Bogomolova, Alexandra M; Nikitin, Artemy A; Dizhe, Ella B; Efremov, Alexander M; Oleinikova, Galina N; Perevozchikov, Andrej P; Orlov, Sergey V

    2016-09-01

    Apolipoprotein A-I (ApoA-I) is the main anti-atherogenic component of human high-density lipoproteins (HDL). ApoA-I gene expression is regulated by several nuclear receptors, which are the sensors for metabolic changes during development of cardiovascular diseases. Activation of nuclear receptor PPARγ has been shown to impact lipid metabolism as well as inflammation. Here, we have shown that synthetic PPARγ agonist GW1929 decreases both ApoA-I mRNA and protein levels in HepG2 cells and the effect of GW1929 on apoA-I gene transcription depends on PPARγ. PPARγ binds to the sites A and C within the hepatic enhancer of apoA-I gene and the negative regulation of apoA-I gene transcription by PPARγ appears to be realized via the site C (-134 to -119). Ligand activation of PPARγ leads to an increase of LXRβ and a decrease of PPARα binding to the apoA-I gene hepatic enhancer in HepG2 cells. GW1929 abolishes the TNFα-mediated decrease of ApoA-I mRNA expression in both HepG2 and Caco-2 cells but does not block TNFα-mediated inhibition of ApoA-I protein secretion by HepG2 cells. These data demonstrate that complex of PPARγ with GW1929 is a negative regulator involved in the control of ApoA-I expression and secretion in human hepatocyte- and enterocyte-like cells. J. Cell. Biochem. 117: 2010-2022, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. SmallSat Database

    NASA Technical Reports Server (NTRS)

    Petropulos, Dolores; Bittner, David; Murawski, Robert; Golden, Bert

    2015-01-01

    The SmallSat has an unrealized potential in both the private industry and in the federal government. Currently over 70 companies, 50 universities and 17 governmental agencies are involved in SmallSat research and development. In 1994, the U.S. Army Missile and Defense mapped the moon using smallSat imagery. Since then Smart Phones have introduced this imagery to the people of the world as diverse industries watched this trend. The deployment cost of smallSats is also greatly reduced compared to traditional satellites due to the fact that multiple units can be deployed in a single mission. Imaging payloads have become more sophisticated, smaller and lighter. In addition, the growth of small technology obtained from private industries has led to the more widespread use of smallSats. This includes greater revisit rates in imagery, significantly lower costs, the ability to update technology more frequently and the ability to decrease vulnerability of enemy attacks. The popularity of smallSats show a changing mentality in this fast paced world of tomorrow. What impact has this created on the NASA communication networks now and in future years? In this project, we are developing the SmallSat Relational Database which can support a simulation of smallSats within the NASA SCaN Compatability Environment for Networks and Integrated Communications (SCENIC) Modeling and Simulation Lab. The NASA Space Communications and Networks (SCaN) Program can use this modeling to project required network support needs in the next 10 to 15 years. The SmallSat Rational Database could model smallSats just as the other SCaN databases model the more traditional larger satellites, with a few exceptions. One being that the smallSat Database is designed to be built-to-order. The SmallSat database holds various hardware configurations that can be used to model a smallSat. It will require significant effort to develop as the research material can only be populated by hand to obtain the unique data

  16. How small are small mutation rates?

    PubMed

    Wu, Bin; Gokhale, Chaitanya S; Wang, Long; Traulsen, Arne

    2012-04-01

    We consider evolutionary game dynamics in a finite population of size N. When mutations are rare, the population is monomorphic most of the time. Occasionally a mutation arises. It can either reach fixation or go extinct. The evolutionary dynamics of the process under small mutation rates can be approximated by an embedded Markov chain on the pure states. Here we analyze how small the mutation rate should be to make the embedded Markov chain a good approximation by calculating the difference between the real stationary distribution and the approximated one. While for a coexistence game, where the best reply to any strategy is the opposite strategy, it is necessary that the mutation rate μ is less than N (-1/2)exp[-N] to ensure that the approximation is good, for all other games, it is sufficient if the mutation rate is smaller than (N ln N)(-1). Our results also hold for a wide class of imitation processes under arbitrary selection intensity.

  17. Small Bowel Adenocarcinoma.

    PubMed

    Aparicio, Thomas; Zaanan, Aziz; Mary, Florence; Afchain, Pauline; Manfredi, Sylvain; Evans, Thomas Ronald Jeffry

    2016-09-01

    Small bowel adenocarcinomas (SBAs) are rare tumors, but their incidence is increasing. The most common primary location is the duodenum. Even though SBAs are more often sporadic, some diseases are risk factors. Early diagnosis of small bowel adenocarcinoma remains difficult, despite significant radiologic and endoscopic progress. After R0 surgical resection, the main prognostic factor is lymph node invasion. An international randomized trial (BALLAD [Benefit of Adjuvant Chemotherapy For Small Bowel Adenocarcinoma] study) will evaluate the benefit of adjuvant chemotherapy. For metastatic disease, retrospectives studies suggest that platinum-based chemotherapy is the most effective treatment. Phase II studies are ongoing to evaluate targeted therapy in metastatic SBA.

  18. Small satellite product assurance

    NASA Astrophysics Data System (ADS)

    Demontlivault, J.; Cadelec, Jacques

    1993-01-01

    In order to increase the interest in small satellites, their cost must be reduced; reducing product assurance costs induced by quality requirements is a major objective. For a logical approach, small satellites are classified in three main categories: satellites for experimental operations with a short lifetime, operational satellites manufactured in small mass with long lifetime requirements, operational satellites (long lifetime required), of which only a few models are produced. The various requirements as regards the product assurance are examined for each satellite category: general requirements for space approach, reliability, electronic components, materials and processes, quality assurance, documentation, tests, and management. Ideal product assurance system integrates quality teams and engineering teams.

  19. 22 CFR 224.39 - Appeal to A.I.D. Administrator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Appeal to A.I.D. Administrator. 224.39 Section... CIVIL REMEDIES ACT § 224.39 Appeal to A.I.D. Administrator. (a) Any defendant who has filed a timely... appeal such decision to the A.I.D. Administrator by filing a notice of appeal with the A.I.D...

  20. 22 CFR 224.39 - Appeal to A.I.D. Administrator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Appeal to A.I.D. Administrator. 224.39 Section... CIVIL REMEDIES ACT § 224.39 Appeal to A.I.D. Administrator. (a) Any defendant who has filed a timely... appeal such decision to the A.I.D. Administrator by filing a notice of appeal with the A.I.D...

  1. 22 CFR 224.39 - Appeal to A.I.D. Administrator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Appeal to A.I.D. Administrator. 224.39 Section... CIVIL REMEDIES ACT § 224.39 Appeal to A.I.D. Administrator. (a) Any defendant who has filed a timely... appeal such decision to the A.I.D. Administrator by filing a notice of appeal with the A.I.D...

  2. 22 CFR 224.39 - Appeal to A.I.D. Administrator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Appeal to A.I.D. Administrator. 224.39 Section... CIVIL REMEDIES ACT § 224.39 Appeal to A.I.D. Administrator. (a) Any defendant who has filed a timely... appeal such decision to the A.I.D. Administrator by filing a notice of appeal with the A.I.D...

  3. 22 CFR 224.39 - Appeal to A.I.D. Administrator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Appeal to A.I.D. Administrator. 224.39 Section... CIVIL REMEDIES ACT § 224.39 Appeal to A.I.D. Administrator. (a) Any defendant who has filed a timely... appeal such decision to the A.I.D. Administrator by filing a notice of appeal with the A.I.D...

  4. High-density lipoprotein apolipoprotein A-I kinetics in obesity.

    PubMed

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

    2005-06-01

    Low plasma concentrations of high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I (apoA-I) are independent predictors of coronary artery disease and are often associated with obesity and the metabolic syndrome. However, the underlying kinetic determinants of HDL metabolism are not well understood. We pooled data from 13 stable isotope studies to investigate the kinetic determinants of apoA-I concentrations in lean and overweight-obese individuals. We also examined the associations of HDL kinetics with age, sex, BMI, fasting plasma glucose, fasting insulin, Homeostasis Model Assessment score, and concentrations of apoA-I, triglycerides, HDL-cholesterol and low-density lipoprotein-cholesterol. Compared with lean individuals, overweight-obese individuals had significantly higher HDL apoA-I fractional catabolic rate (0.21+/-0.01 vs. 0.33+/-0.01 pools/d; p<0.001) and production rate (PR; 11.3+/-4.4 vs. 15.8+/-2.77 mg/kg per day; p=0.001). In the lean group, HDL apoA-I PR was significantly associated with apoA-I concentration (r=0.455, p=0.004), whereas in the overweight-obese group, both HDL apoA-I fractional catabolic rate (r=-0.396, p=0.050) and HDL apoA-I PR (r=0.399, p=0.048) were significantly associated with apoA-I concentration. After adjustment for fasting insulin or Homeostasis Model Assessment score, HDL apoA-I PR was an independent predictor of apoA-I concentration. In overweight-obese subjects, hypercatabolism of apoA-I is paralleled by an increased production of apoA-I, with HDL apoA-I PR being the stronger determinant of apoA-I concentration. This could have therapeutic implications for the management of dyslipidemia in individuals with low plasma HDL-cholesterol.

  5. 22 CFR 214.22 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Responsibilities within A.I.D. 214.22 Section... Termination and Renewal of Advisory Committees § 214.22 Responsibilities within A.I.D. Responsibilities within A.I.D. for the renewal of advisory committees are as follows: (a) The Office or Bureau through which...

  6. 22 CFR 214.22 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Responsibilities within A.I.D. 214.22 Section... Termination and Renewal of Advisory Committees § 214.22 Responsibilities within A.I.D. Responsibilities within A.I.D. for the renewal of advisory committees are as follows: (a) The Office or Bureau through which...

  7. 22 CFR 214.22 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Responsibilities within A.I.D. 214.22 Section... Termination and Renewal of Advisory Committees § 214.22 Responsibilities within A.I.D. Responsibilities within A.I.D. for the renewal of advisory committees are as follows: (a) The Office or Bureau through which...

  8. 22 CFR 214.22 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Responsibilities within A.I.D. 214.22 Section... Termination and Renewal of Advisory Committees § 214.22 Responsibilities within A.I.D. Responsibilities within A.I.D. for the renewal of advisory committees are as follows: (a) The Office or Bureau through which...

  9. 22 CFR 214.22 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Responsibilities within A.I.D. 214.22 Section... Termination and Renewal of Advisory Committees § 214.22 Responsibilities within A.I.D. Responsibilities within A.I.D. for the renewal of advisory committees are as follows: (a) The Office or Bureau through which...

  10. 22 CFR 221.24 - Subrogation of A.I.D.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Subrogation of A.I.D. 221.24 Section 221.24 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS Procedure for Obtaining Compensation § 221.24 Subrogation of A.I.D. In the event of payment by A.I.D. to...

  11. 22 CFR 221.24 - Subrogation of A.I.D.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Subrogation of A.I.D. 221.24 Section 221.24 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS Procedure for Obtaining Compensation § 221.24 Subrogation of A.I.D. In the event of payment by A.I.D. to...

  12. 22 CFR 221.24 - Subrogation of A.I.D.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Subrogation of A.I.D. 221.24 Section 221.24 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS Procedure for Obtaining Compensation § 221.24 Subrogation of A.I.D. In the event of payment by A.I.D. to...

  13. 22 CFR 221.24 - Subrogation of A.I.D.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Subrogation of A.I.D. 221.24 Section 221.24 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS Procedure for Obtaining Compensation § 221.24 Subrogation of A.I.D. In the event of payment by A.I.D. to...

  14. 22 CFR 221.24 - Subrogation of A.I.D.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Subrogation of A.I.D. 221.24 Section 221.24 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS Procedure for Obtaining Compensation § 221.24 Subrogation of A.I.D. In the event of payment by A.I.D. to...

  15. Small islands adrift

    NASA Astrophysics Data System (ADS)

    Petherick, Anna

    2015-07-01

    With the charismatic former president of the Maldives, Mohamed Nasheed, behind bars on a widely derided terrorism charge, Anna Petherick asks whether small island states can really make themselves heard in Paris.

  16. Successful Small Study Groups

    ERIC Educational Resources Information Center

    Francke, Amiel W.; Kaplan, Walter J.

    1977-01-01

    The authors examine their own experiences with the small study group method used in professional continuing education in the optometric profession, offering some observations and tentative conclusions for other professionals considering the method. (WL)

  17. Boiling from small cylinders.

    NASA Technical Reports Server (NTRS)

    Bakhru, N.; Lienhard, J. H.

    1972-01-01

    Heat transfer is observed as a function of temperature on small horizontal wires in water and four organic liquids. When the wire radius is sufficiently small, the hydrodynamic transitions in the boiling curve disappear and the curve becomes monotonic. Three modes of heat removal are identified for the monotonic curve and described analytically: a natural convection mode, a mixed film boiling and natural convection mode, and a pure film boiling mode. Nucleate boiling does not occur on the small wires. The study was motivated by an interest in predicting the behavior of large heaters at low gravity. The application of the present results to such circumstances is therefore discussed. It is proposed that the peak and minimum heat fluxes will vanish at low gravity as well as on small wires.

  18. Big Obscures Small

    NASA Image and Video Library

    2010-02-17

    NASA Cassini spacecraft captures a mutual event between Titan and Mimas in front of a backdrop of the planet rings. This image was snapped shortly before Saturn largest moon passed in front of and occulted the small moon Mimas.

  19. Small RNAs in spermatogenesis.

    PubMed

    Yadav, Ram Prakash; Kotaja, Noora

    2014-01-25

    Spermatogenesis is characterized by meiotic divisions and major morphological changes to produce spermatozoa that are capable of independent movement and fertilization of an egg. Male germ cell differentiation is governed by orchestrated, phase-specific gene expression patterns that are tightly controlled at transcriptional and post-transcriptional level. Post-transcriptional regulation of protein-coding mRNAs becomes prominent during the late steps of spermatogenesis when the compacting sperm nucleus becomes transcriptionally inhibited. Small non-coding RNAs are important regulators of gene expression that mainly function post-transcriptionally to control the properties of their target mRNAs. Male germ cells express several classes of small RNAs, including Dicer-dependent microRNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs), as well as Dicer-independent piwi-interacting RNAs (piRNAs). Increasing evidence supports the essential role of small RNA-mediated RNA regulation in normal spermatogenesis and male fertility.

  20. Small bowel resection - slideshow

    MedlinePlus

    ... Overview The small intestine absorbs much of the liquid from foods. There are three parts of the ... Specialists of Georgia, Austell, GA. Review provided by VeriMed Healthcare Network. Also reviewed ...

  1. Neptune's small satellites

    NASA Astrophysics Data System (ADS)

    Thomas, P.

    1992-04-01

    The small satellites of Neptune and other planets discovered during the Voyager 2 mission are discussed in terms of their composition and relationship to the planetary systems. The satellite Proteus is described in terms of its orbit, five other satellites are described, and they are compared to ther small satellites and systems. Neptune's satellites are hypothesized to be related to the ring system, and the satellite Galatea is related to the confinement of the rings.

  2. Small woodland ownership management

    Treesearch

    Albert J. Childs

    1977-01-01

    Small woodlot ownerships are a commodity on the real estate market which have cycled through a supply and demand curve on a somewhat irregular basis. In order to have some understanding of what it is we are talking about, it is necessary to define what a small woodlot is, and where it may be found. In size these parcels can range from ten acres to fifteen acres on up...

  3. Small Business Research Program

    NASA Astrophysics Data System (ADS)

    The U.S. Department of Energy (DOE) invites small businesses, or those with 500 employees or less, to write for a copy of its Small Business Innovation Research (SBIR) program solicitation, to be issued January 2, 1985. To receive a copy, contact the SBIR Program Manager, U.S. Department of Energy, Washington, DC 20545; telephone 301-353-5707. The closing date for this solicitation is March 15, 1985.

  4. Small-x physics

    SciTech Connect

    Mueller, A.H.

    1997-06-01

    After a brief review of the kinematics of deep inelastic lepton-proton scattering, the parton model is described. Small-x behavior coming from DGLAP evolution and from BFKL evolution is discussed, and the two types of evolution are contrasted and compared. Then a more detailed discussion of BFKL dynamics is given. The phenomenology of small-x physics is discussed with an emphasis on ways in which BFKL dynamics may be discussed and measured. 45 refs., 12 figs.

  5. Surface behavior of apolipoprotein A-I and its deletion mutants at model lipoprotein interfaces

    PubMed Central

    Wang, Libo; Mei, Xiaohu; Atkinson, David; Small, Donald M.

    2014-01-01

    Apolipoprotein A-I (apoA-I) has a great conformational flexibility to exist in lipid-free, lipid-poor, and lipid-bound states during lipid metabolism. To address the lipid binding and the dynamic desorption behavior of apoA-I at lipoprotein surfaces, apoA-I, Δ(185-243)apoA-I, and Δ(1-59)(185-243)apoA-I were studied at triolein/water and phosphatidylcholine/triolein/water interfaces with special attention to surface pressure. All three proteins are surface active to both interfaces lowering the interfacial tension and thus increasing the surface pressure to modify the interfaces. Δ(185-243)apoA-I adsorbs much more slowly and lowers the interfacial tension less than full-length apoA-I, confirming that the C-terminal domain (residues 185-243) initiates the lipid binding. Δ(1-59)(185-243)apoA-I binds more rapidly and lowers the interfacial tension more than Δ(185-243)apoA-I, suggesting that destabilizing the N-terminal α-helical bundle (residues 1-185) restores lipid binding. The three proteins desorb from both interfaces at different surface pressures revealing that different domains of apoA-I possess different lipid affinity. Δ(1-59)(185-243)apoA-I desorbs at lower pressures compared with apoA-I and Δ(185-243)apoA-I indicating that it is missing a strong lipid association motif. We propose that during lipoprotein remodeling, surface pressure mediates the adsorption and partial or full desorption of apoA-I allowing it to exchange among different lipoproteins and adopt various conformations to facilitate its multiple functions. PMID:24308948

  6. Nucleotide sequence and the encoded amino acids of human apolipoprotein A-I mRNA.

    PubMed Central

    Law, S W; Brewer, H B

    1984-01-01

    The cDNA clones encoding the precursor form of human liver apolipoprotein A-I (apoA-I), preproapoA-I, have been isolated from a cDNA library. A 17-base synthetic oligonucleotide based on residues 108-113 of apoA-I and a 26-base primer-extended, dideoxynucleotide-terminated cDNA were used as hybridization probes to select for recombinant plasmids bearing the apoA-I sequence. The complete nucleic acid sequence of human liver preproapoA-I has been determined by analysis of the cloned cDNA. The sequence is composed of 801 nucleotides encoding 267 amino acid residues. PreproapoA-I contains an 18-amino-acid prepeptide and a 6-amino-acid propeptide connected to the amino terminus of the 243-amino acid mature apoA-I. Southern blotting analysis of chromosomal DNA obtained from peripheral blood indicated the apoA-I gene is contained in a 2.1-kilobase-pair Pst I fragment and there is no gross difference in structural organization between the normal apoA-I gene and the Tangier disease apoA-I gene. Images PMID:6198645

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

    SciTech Connect

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

    1989-07-01

    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.

  8. MINERVA: Small Planets from Small Telescopes

    NASA Astrophysics Data System (ADS)

    Wittenmyer, Robert A.; Johnson, John Asher; Wright, Jason; McCrady, Nate; Swift, Jonathan; Bottom, Michael; Plavchan, Peter; Riddle, Reed; Muirhead, Philip S.; Herzig, Erich; Myles, Justin; Blake, Cullen H.; Eastman, Jason; Beatty, Thomas G.; Lin, Brian; Zhao, Ming; Gardner, Paul; Falco, Emilio; Criswell, Stephen; Nava, Chantanelle; Robinson, Connor; Hedrick, Richard; Ivarsen, Kevin; Hjelstrom, Annie; de Vera, Jon; Szentgyorgyi, Andrew

    2015-09-01

    The Kepler mission has shown that small planets are extremely common. It is likely that nearly every star in the sky hosts at least one rocky planet. We just need to look hard enough-but this requires vast amounts of telescope time. MINERVA (MINiature Exoplanet Radial Velocity Array) is a dedicated exoplanet observatory with the primary goal of discovering rocky, Earth-like planets orbiting in the habitable zone of bright, nearby stars. The MINERVA team is a collaboration among UNSW Australia, Harvard-Smithsonian Center for Astrophysics, Penn State University, University of Montana, and the California Institute of Technology. The four-telescope MINERVA array will be sited at the F.L. Whipple Observatory on Mt Hopkins in Arizona, USA. Full science operations will begin in mid-2015 with all four telescopes and a stabilised spectrograph capable of high-precision Doppler velocity measurements. We will observe ~100 of the nearest, brightest, Sun-like stars every night for at least five years. Detailed simulations of the target list and survey strategy lead us to expect new low-mass planets.

  9. Small Intestinal Infections.

    PubMed

    Munot, Khushboo; Kotler, Donald P

    2016-06-01

    Small intestinal infections are extremely common worldwide. They may be bacterial, viral, or parasitic in etiology. Most are foodborne or waterborne, with specific etiologies differing by region and with diverse pathophysiologies. Very young, very old, and immune-deficient individuals are the most vulnerable to morbidity or mortality from small intestinal infections. There have been significant advances in diagnostic sophistication with the development and early application of molecular diagnostic assays, though these tests have not become mainstream. The lack of rapid diagnoses combined with the self-limited nature of small intestinal infections has hampered the development of specific and effective treatments other than oral rehydration. Antibiotics are not indicated in the absence of an etiologic diagnosis, and not at all in the case of some infections.

  10. A Small as Possible

    NASA Technical Reports Server (NTRS)

    Tibbitts, Scott

    2003-01-01

    This story begins with a bit of serendipity: I was on a trip to see a Shuttle launch and I happened to sit next to a guy who was in charge of batteries for Space Systems/Loral. He told me that they needed to create a new battery bypass switch, the device that takes a battery out of commission if it goes bad. After discussing the conversation back at my company, we decided that we could create the switch. We contacted the folks at Loral and they said, 'Okay, let s see what you can come up with. We need it as small as possible.' We asked, 'How small?' They said, 'We need it as small as you can possibly make it.'

  11. Small Animal Retinal Imaging

    NASA Astrophysics Data System (ADS)

    Choi, WooJhon; Drexler, Wolfgang; Fujimoto, James G.

    Developing and validating new techniques and methods for small animal imaging is an important research area because there are many small animal models of retinal diseases such as diabetic retinopathy, age-related macular degeneration, and glaucoma [1-6]. Because the retina is a multilayered structure with distinct abnormalities occurring in different intraretinal layers at different stages of disease progression, there is a need for imaging techniques that enable visualization of these layers individually at different time points. Although postmortem histology and ultrastructural analysis can be performed for investigating microscopic changes in the retina in small animal models, this requires sacrificing animals, which makes repeated assessment of the same animal at different time points impossible and increases the number of animals required. Furthermore, some retinal processes such as neurovascular coupling cannot be fully characterized postmortem.

  12. Small-world networks

    NASA Astrophysics Data System (ADS)

    Strogatz, Steven

    Everyone is familiar with the small-world phenomenon: soon after meeting a stranger, we are often suprised to discover that we have a mutual friend, or that we are somehow linked by a short chain of friends. In this talk, I'll present evidence that the small-world phenomenon is more than a curiosity of social networks — it is actually a general property of large, sparse networks whose topology is neither completely regular nor completely random. To check this idea, Duncan Watts and I have analyzed three networks of scientific interest: the neural network of the nematode worm C. elegans, the electrical power grid of the western United States, and the collaboration graph of actors in feature films. All three are small worlds, in the sense that the average number of "handshakes" separating any two members is extremely small (close to the theoretical lower limit set by a random graph). Yet at the same time, all three networks exhibit much more local clustering than a random net, demonstrating that they are not random. I'll also discuss a class of model networks that interpolate between regular lattices and random graphs. Previous theoretical research on complex systems in a wide range of disciplines has focused almost exclusively on networks that are either regular or random. Real networks often lie somewhere in between. Our mathematical model shows that networks in this middle ground tend to exhibit the small-world phenomenon, thanks to the presence of a few long-range edges that link parts of the graph that would otherwise be far apart. Furthermore, we find that when various dynamical systems are coupled in a small-world fashion, they exhibit much greater propagation speed, computational power, and synchronizability than their locally connected, regular counterparts. We explore the implications of these results for simple models of disease spreading, global computation in cellular automata, and collective locking of biological oscillators.

  13. Programming in the small.

    PubMed

    Gersten, David B; Langer, Steve G

    2011-02-01

    Academic medical centers, in general, and radiation oncology research, in particular, rely heavily on custom software tools and applications. The code development is typically the responsibility of a single individual or at most a small team. Often these individuals are not professional programmers but physicists, students, and physicians. While they possess domain expertise and algorithm knowledge, they often are not fully aware of general "safe coding" practices--nor do they need the full complexity familiar in large commercial software projects to succeed. Rather, some simple guidelines we refer to as "programming in the small" can be used.

  14. Tracking Small Artists

    NASA Astrophysics Data System (ADS)

    Russell, James C.; Klette, Reinhard; Chen, Chia-Yen

    Tracks of small animals are important in environmental surveillance, where pattern recognition algorithms allow species identification of the individuals creating tracks. These individuals can also be seen as artists, presented in their natural environments with a canvas upon which they can make prints. We present tracks of small mammals and reptiles which have been collected for identification purposes, and re-interpret them from an esthetic point of view. We re-classify these tracks not by their geometric qualities as pattern recognition algorithms would, but through interpreting the 'artist', their brush strokes and intensity. We describe the algorithms used to enhance and present the work of the 'artists'.

  15. Small Bowel Transplant

    PubMed Central

    2003-01-01

    EXECUTIVE SUMMARY Objective The Medical Advisory Secretariat undertook a review of the evidence on the effectiveness and cost-effectiveness of small bowel transplant in the treatment of intestinal failure. Small Bowel Transplantation Intestinal failure is the loss of absorptive capacity of the small intestine that results in an inability to meet the nutrient and fluid requirements of the body via the enteral route. Patients with intestinal failure usually receive nutrients intravenously, a procedure known as parenteral nutrition. However, long-term parenteral nutrition is associated with complications including liver failure and loss of venous access due to recurrent infections. Small bowel transplant is the transplantation of a cadaveric intestinal allograft for the purpose of restoring intestinal function in patients with irreversible intestinal failure. The transplant may involve the small intestine alone (isolated small bowel ISB), the small intestine and the liver (SB-L) when there is irreversible liver failure, or multiple organs including the small bowel (multivisceral MV or cluster). Although living related donor transplant is being investigated at a limited number of centres, cadaveric donors have been used in most small bowel transplants. The actual transplant procedure takes approximately 12-18 hours. After intestinal transplant, the patient is generally placed on prophylactic antibiotic medication and immunosuppressive regimen that, in the majority of cases, would include tacrolimus, corticosteroids and an induction agent. Close monitoring for infection and rejection are essential for early treatment. Medical Advisory Secretariat Review The Medical Advisory Secretariat undertook a review of 35 reports from 9 case series and 1 international registry. Sample size of the individual studies ranged from 9 to 155. As of May 2001, 651 patients had received small bowel transplant procedures worldwide. According to information from the Canadian Organ Replacement

  16. RISK and SAFE Signaling Pathway Involvement in Apolipoprotein A-I-Induced Cardioprotection

    PubMed Central

    Kalakech, Hussein; Hibert, Pierre; Prunier-Mirebeau, Delphine; Tamareille, Sophie; Letournel, Franck; Macchi, Laurent; Pinet, Florence; Furber, Alain; Prunier, Fabrice

    2014-01-01

    Recent findings indicate that apolipoprotein A-I (ApoA-I) may be a protective humoral mediator involved in remote ischemic preconditioning (RIPC). This study sought to determine if ApoA-I mediates its protective effects via the RISK and SAFE signaling pathways implicated in RIPC. Wistar rats were allocated to one of the following groups. Control: rats were subjected to myocardial ischemia/reperfusion (I/R) without any further intervention; RIPC: four cycles of limb I/R were applied prior to myocardial ischemia; ApoA-I: 10 mg/Kg of ApoA-I were intravenously injected prior to myocardial ischemia; ApoA-I + inhibitor: pharmacological inhibitors of RISK/SAFE pro-survival kinase (Akt, ERK1/2 and STAT-3) were administered prior to ApoA-I injection. Infarct size was significantly reduced in the RIPC group compared to Control. Similarly, ApoA-I injection efficiently protected the heart, recapitulating RIPC-induced cardioprotection. The ApoA-I protective effect was associated with Akt and GSK-3β phosphorylation and substantially inhibited by pretreatment with Akt and ERK1/2 inhibitors. Pretreatment with ApoA-I in a rat model of I/R recapitulates RIPC-induced cardioprotection and shares some similar molecular mechanisms with those of RIPC-involved protection of the heart. PMID:25237809

  17. How Small are Small Stars Really?

    NASA Astrophysics Data System (ADS)

    2002-11-01

    VLT Interferometer Measures the Size of Proxima Centauri and Other Nearby Stars [1] Summary At a distance of only 4.2 light-years, Proxima Centauri is the nearest star to the Sun currently known [2]. It is visible as an 11-magnitude object in the southern constellation of Centaurus and is the faintest member of a triple system, together with Alpha Centauri , the brightest (double) star in this constellation. Proxima Centauri is a very-low-mass star, in fact barely massive enough to burn hydrogen to helium in its interior. It is about seven times smaller than the Sun, and the surface temperature is "only" about 3000 degrees, about half of that of our own star. Consequently, it is also much fainter - the intrinsic brightness is only 1/150th of that of our Sun. Low-mass stars are very interesting objects , also because the physical conditions in their interiors have much in common with those of giant planets, like Jupiter in our solar system. A determination of the sizes of the smallest stars has been impossible until now because of their general faintness and lack of adequate instrumentation. However, astronomers have long been keen to move forward in this direction, since such measurements would provide indirect, crucial information about the behaviour of matter under extreme conditions. When the first observations with the VLT Interferometer (VLTI), combining the light from two of the 8.2-m VLT Unit Telescopes (ANTU and MELIPAL), were made one year ago ( ESO PR 23/01 ), interferometric measurements were also obtained of Proxima Centauri . They formed part of the VLTI commissioning and the data were soon released to the ESO community, cf. the special website. Now, an international team of astronomers from Switzerland, France and ESO/Chile has successfully analysed these observations by means of newly developed, advanced software. For the first time ever, they obtained a highly accurate measurement of the size of such a small star . Three other small stars were also

  18. Small Public Library Management

    ERIC Educational Resources Information Center

    Pearlmutter, Jane; Nelson, Paul

    2012-01-01

    Anyone at the helm of a small public library knows that every little detail counts. But juggling the responsibilities that are part and parcel of the job is far from easy. Finally, here's a handbook that includes everything administrators need to keep a handle on library operations, freeing them up to streamline and improve how the organization…

  19. Small fibre neuropathy.

    PubMed

    Cazzato, Daniele; Lauria, Giuseppe

    2017-10-01

    To provide a review on the state-of-art of clinical features, diagnostics, genetics and treatments of small fibre neuropathy (SFN). The spectrum of clinical features has been widened from the classical presentation of burning feet as length-dependent SFN to that of small fibre dysfunction and/or degeneration associated with focal, diffuse and episodic neuropathic pain syndromes. The involvement of small nerve fibres in neurodegenerative diseases has been further defined, challenging the relationship between neuropathic pain symptoms and small fibre loss. The clinical reliability of skin biopsy has been strengthened by the availability of normative values for both the immunohistochemistry techniques used and their comparison, and by side and short-term follow-up analyses. Corneal confocal microscopy has implemented its diagnostic potentiality because of the availability of age-adjusted and sex-adjusted normative values. Genetic studies expanded the panel on genes involved in SFN because of the discovery of new mutations in SCN10A and SCN11A, besides the first found in SCN9A, and identification of mutations in COL6A5 in patients with itching. In the last 5 years, the chapter of SFN has been widened by new clinical and genetics descriptions leading to a more comprehensive approach to patients in clinical practice and research.

  20. Small School Distributive Education.

    ERIC Educational Resources Information Center

    Barnes, Bill

    Information on an atypical 1966-67 Distributive Education pilot program in New Mexico was given. The program was unique since one instructor conducted this program in two schools which were in separate rural districts (Dexter and Hagerman). Since both communities were primarily agricultural, with small student populations, the cost of such a…

  1. Small satellite radiometric measurements

    SciTech Connect

    Weber, P.G.

    1991-01-01

    A critical need for the Mission to Planet Earth is to provide continuous, well-calibrated radiometric data for the radiation budget. This paper describes a new, compact, flexible radiometer which will provide both spectrally integrated data and data in selected spectral bands. The radiometer design is suitable for use on small satellites, aircraft, or remotely piloted vehicles (RPVs). 12 refs., 2 figs.

  2. Small Wonders Close Encounters

    ERIC Educational Resources Information Center

    Kniseley, MacGregor; Capraro, Karen

    2013-01-01

    This article introduces students to the world of digital microscopy. Looking at small objects through a digital microscope is like traveling through a foreign country for the first time. The experience is new, engaging, and exciting. A handheld digital microscope is an essential tool in a 21st century teacher's toolkit and the perfect tool to…

  3. Small Bowel Bleeding

    MedlinePlus

    ... of the small bowel, known as the jejunum. X-ray studies X-ray studies are sometimes used in people with bleeding ... that can be seen by standard or specialized x-ray studies, such as tumors. There are three x- ...

  4. Deburring small intersecting holes

    SciTech Connect

    Gillespie, L.K.

    1980-08-01

    Deburring intersecting holes is one of the most difficult deburring tasks faced by many industries. Only 14 of the 37 major deburring processes are applicable to most intersecting hole applications. Only five of these are normally applicable to small or miniature holes. Basic process capabilities and techniques used as a function of hole sizes and intersection depths are summarized.

  5. Small Town Girl.

    ERIC Educational Resources Information Center

    Horning, Kathleen T.

    2000-01-01

    This interview with Kimberly Willis Holt, an author of young adult fiction who recently won the National Book Award for Young People's Literature, discusses her background, how she began her writing career, childhood influences, small-town life, and how she develops her characters. (LRW)

  6. Small Schools Reform Narratives

    ERIC Educational Resources Information Center

    Lehman, Beth M.; Berghoff, Beth

    2013-01-01

    This study explored complicated personal narratives of school reform generated by participants in response to a particular small schools reform initiative. Narrative data was dialogically generated in interviews with nine past participants of an urban high school conversion project planned and implemented over a span of five years toward the goal…

  7. Small College AI.

    ERIC Educational Resources Information Center

    Kollmeier, Harold H.

    The feasibility of conducting computer science courses in artificial intelligence at a small liberal arts college is examined. The following problems are examined in detail: isolation; student abililty, motivation and expectation; equipment; and faculty readiness. Providing a focus to the discussion, three issues are addressed in terms of…

  8. Closed Small Cell Clouds

    Atmospheric Science Data Center

    2013-04-19

    ... (right)   The structure of tightly packed "closed cells" in a layer of marine stratocumulus over the southeastern Pacific Ocean ... into interesting structures such as those shown here. These cells are notably small, with diameters ranging from 10-15 kilometers, instead ...

  9. Small Business Bibliography.

    ERIC Educational Resources Information Center

    Anderson, Wendell, Ed.

    Intended as a resource for both experienced businesspeople and those new to business, this annotated bibliography provides a list of books, pamphlets, periodicals, and videotapes of value in solving specific business problems. The bibliography begins with a list of resources recommended for the library of every small business and a survey of…

  10. Modeling Small Group Learning

    ERIC Educational Resources Information Center

    Draskovic, I.; Holdrinet, R.; Bulte, J.; Bolhuis, S.; Van Leeuwe, J.

    2004-01-01

    This article presents findings from an empirical study on the relations between the variables comprising learning mechanisms in small collaborative groups. Variables comprising the central learning mechanisms component were "task related interactions," "knowledge elaborations," and "subjective estimation of knowledge acquisition." Student related…

  11. Small Business Bibliography.

    ERIC Educational Resources Information Center

    Anderson, Wendell, Ed.

    Intended as a resource for both experienced businesspeople and those new to business, this annotated bibliography provides a list of books, pamphlets, periodicals, and videotapes of value in solving specific business problems. The bibliography begins with a list of resources recommended for the library of every small business and a survey of…

  12. Automating Small Libraries.

    ERIC Educational Resources Information Center

    Swan, James

    1996-01-01

    Presents a four-phase plan for small libraries strategizing for automation: inventory and weeding, data conversion, implementation, and enhancements. Other topics include selecting a system, MARC records, compatibility, ease of use, industry standards, searching capabilities, support services, system security, screen displays, circulation modules,…

  13. Small Public Library Management

    ERIC Educational Resources Information Center

    Pearlmutter, Jane; Nelson, Paul

    2012-01-01

    Anyone at the helm of a small public library knows that every little detail counts. But juggling the responsibilities that are part and parcel of the job is far from easy. Finally, here's a handbook that includes everything administrators need to keep a handle on library operations, freeing them up to streamline and improve how the organization…

  14. Small Business Innovations

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Under an Army Small Business Innovation Research (SBIR) grant, Symbiotics, Inc. developed a software system that permits users to upgrade products from standalone applications so they can communicate in a distributed computing environment. Under a subsequent NASA SBIR grant, Symbiotics added additional tools to the SOCIAL product to enable NASA to coordinate conventional systems for planning Shuttle launch support operations. Using SOCIAL, data may be shared among applications in a computer network even when the applications are written in different programming languages. The product was introduced to the commercial market in 1993 and is used to monitor and control equipment for operation support and to integrate financial networks. The SBIR program was established to increase small business participation in federal R&D activities and to transfer government research to industry. InQuisiX is a reuse library providing high performance classification, cataloging, searching, browsing, retrieval and synthesis capabilities. These form the foundation for software reuse, producing higher quality software at lower cost and in less time. Software Productivity Solutions, Inc. developed the technology under Small Business Innovation Research (SBIR) projects funded by NASA and the Army and is marketing InQuisiX in conjunction with Science Applications International Corporation (SAIC). The SBIR program was established to increase small business participation in federal R&D activities and to transfer government research to industry.

  15. Small Town Renewal Manual.

    ERIC Educational Resources Information Center

    Kenyon, Peter

    Over the last 2 decades, the loss of population and businesses in many small, inland, and remote Australian rural communities has intensified, largely because of the stress and uncertainty of volatile world commodity markets. This manual presents a range of survival and revival strategies that some communities have used to build resilient…

  16. Small Gas Engine Repair.

    ERIC Educational Resources Information Center

    Connecticut State Dept. of Education, Hartford. Div. of Vocational-Technical Schools.

    Instructional materials are provided for a small gas engine course. A list of objectives appears first, followed by a list of internal parts and skills/competencies related to those parts for engine work, ignition and electrical systems, fuel system, crankcase lubrication system, arc welding skills, and gas welding skills. Outlines are provided…

  17. Small Wonders Close Encounters

    ERIC Educational Resources Information Center

    Kniseley, MacGregor; Capraro, Karen

    2013-01-01

    This article introduces students to the world of digital microscopy. Looking at small objects through a digital microscope is like traveling through a foreign country for the first time. The experience is new, engaging, and exciting. A handheld digital microscope is an essential tool in a 21st century teacher's toolkit and the perfect tool to…

  18. Small Schools Reform Narratives

    ERIC Educational Resources Information Center

    Lehman, Beth M.; Berghoff, Beth

    2013-01-01

    This study explored complicated personal narratives of school reform generated by participants in response to a particular small schools reform initiative. Narrative data was dialogically generated in interviews with nine past participants of an urban high school conversion project planned and implemented over a span of five years toward the goal…

  19. Measuring Small Leak Holes

    NASA Technical Reports Server (NTRS)

    Koch, D. E.; Stephenson, J. G.

    1983-01-01

    Hole sizes deduced from pressure measurements. Measuring apparatus consists of pitot tube attached to water-filled manometer. Compartment tested is pressurized with air. Pitot probe placed at known distance from leak. Dynamic pressure of jet measured at that point and static pressure measured in compartment. Useful in situations in which small leaks are tolerable but large leaks are not.

  20. Swedish small satellites

    NASA Astrophysics Data System (ADS)

    Lundahl, K.; von Scheele, F.

    2004-11-01

    In 1986 the first Swedish small satellite VIKING was launched on the Ariane 1 rocket together with the French remote sensing satellite SPOT-1. This paper describes the development of Swedish small satellites in an international framework. The satellites have delivered excellent scientific data to a low cost by using e.g. streamlined project organisations, competitive procurement programs and piggy-back launch opportunities. The first micro satellite Astrid-1 was launched in January 1995 and was followed by the launch of Astrid-2 in December 1998. The capable Odin small satellite was launched in February 2001. SSC was also contracted for ESA's SMART-1 probe destined to the Moon. SMART-1, launched in September 2003, is used for both research and as a technology demonstrator for future projects. Future proposed projects include micro and small satellites for climate research as the Atmosphere and Climate Explorer Plus (ACE+), the Stratosphere-Troposphere Exchange And climate Monitor (STEAM) and PRISMA, a technology demonstrator for formation flying, new propulsion system and commercial development methods.

  1. Small Area Forecast Evaluation.

    ERIC Educational Resources Information Center

    Southeast Michigan Council of Governments, Detroit.

    The results of a small area forecast with regard to household composition, population and employment distribution, development and school costs, environmental impact, and transportation in Southeast Michigan are evaluated in this report. The role of public policy in influencing the community demography by the year 2000 is considered by…

  2. Small Group Research

    ERIC Educational Resources Information Center

    McGrath, Joseph E.

    1978-01-01

    Summarizes research on small group processes by giving a comprehensive account of the types of variables primarily studied in the laboratory. These include group structure, group composition, group size, and group relations. Considers effects of power, leadership, conformity to social norms, and role relationships. (Author/AV)

  3. Small is beautiful

    NASA Astrophysics Data System (ADS)

    Bannister, Nigel; Eves, Stuart

    2009-12-01

    MEETING REPORT While the great space observatories have provided much of the headline news in astronomy and astrophysics in recent years, they are not the whole story. Nigel Bannister reports on an RAS Specialist Discussion Meeting on ``Astronomy with Small Satellites''.

  4. 22 CFR 204.22 - Right of A.I.D. to cure default.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Right of A.I.D. to cure default. 204.22 Section... CONDITIONS Procedure for Obtaining Compensation § 204.22 Right of A.I.D. to cure default. Within sixty (60) days after the Date of Application for Compensation, A.I.D. may at any time make payments to the Lender...

  5. 22 CFR 204.22 - Right of A.I.D. to cure default.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Right of A.I.D. to cure default. 204.22 Section... CONDITIONS Procedure for Obtaining Compensation § 204.22 Right of A.I.D. to cure default. Within sixty (60) days after the Date of Application for Compensation, A.I.D. may at any time make payments to the Lender...

  6. 22 CFR 204.22 - Right of A.I.D. to cure default.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Right of A.I.D. to cure default. 204.22 Section... CONDITIONS Procedure for Obtaining Compensation § 204.22 Right of A.I.D. to cure default. Within sixty (60) days after the Date of Application for Compensation, A.I.D. may at any time make payments to the Lender...

  7. 22 CFR 204.22 - Right of A.I.D. to cure default.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Right of A.I.D. to cure default. 204.22 Section... CONDITIONS Procedure for Obtaining Compensation § 204.22 Right of A.I.D. to cure default. Within sixty (60) days after the Date of Application for Compensation, A.I.D. may at any time make payments to the Lender...

  8. 22 CFR 204.22 - Right of A.I.D. to cure default.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Right of A.I.D. to cure default. 204.22 Section... CONDITIONS Procedure for Obtaining Compensation § 204.22 Right of A.I.D. to cure default. Within sixty (60) days after the Date of Application for Compensation, A.I.D. may at any time make payments to the Lender...

  9. Apolipoprotein A-I mutant proteins having cysteine substitutions and polynucleotides encoding same

    DOEpatents

    Oda, Michael N.; Forte, Trudy M.

    2007-05-29

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

  10. Induction of apolipoprotein A-I gene expression by black seed (Nigella sativa) extracts.

    PubMed

    Haas, Michael J; Onstead-Haas, Luisa M; Naem, Emad; Wong, Norman C W; Mooradian, Arshag D

    2014-09-01

    Black seed [Nigella sativa L. (Ranunculaceae)] has been shown in animal models to lower serum cholesterol levels. In order to determine if extracts from black seed have any effects on high-density lipoprotein (HDL), we characterized the effects of black seed extract on apolipoprotein A-I (apo A-I) gene expression, the primary protein component of HDL. Hepatocytes (HepG2) and intestinal cells (Caco-2) were treated with black seed extracts, and Apo A-I, peroxisome proliferator-activated receptor α (PPARα), and retinoid-x-receptor α (RXRα) were measured by Western blot analysis. Apo A-I mRNA levels were measured by quantitative real-time polymerase chain reaction and apo A-I gene transcription was measured by transient transfection of apo A-I reporter plasmids. Extracts from black seeds significantly increased hepatic and intestinal apo A-I secretion, as well as apo A-I mRNA and gene promoter activity. This effect required a PPARα binding site in the apo A-I gene promoter. Treatment of the extract with either heat or trypsin had no effect on its ability to induce apo A-I secretion. Treatment with black seed extract induced PPARα expression 9-fold and RXRα expression 2.5-fold. Furthermore, the addition of PPARα siRNA but not a control siRNA prevented some but not all the positive effects of black seed on apo A-I secretion. Black seed extract is a potent inducer of apo A-I gene expression, presumably by enhancing PPARα/RXRα expression. We conclude that black seed may have beneficial effects in treating dyslipidemia and coronary heart disease.

  11. The unsolved mystery of apoA-I recycling in adipocyte.

    PubMed

    Wang, Shuai; Peng, Dao-quan; Yi, Yuhong

    2016-02-24

    As the major storage site for triglycerides and free cholesterol, adipose tissue plays a central role in energy metabolism. ApoA-I is the main constituent of HDL and plays an important role in removal of excess cholesterol from peripheral tissues. Recently, multiple studies have shown beneficial effects of apoA-I on adipose metabolism and function. ApoA-I was reported to improve insulin sensitivity and exert anti-inflammatory, anti-obesity effect in animal studies. Interestingly, Uptake and resecretion of apoA-I by adipocytes has been detected. However, the significance of apoA-I recycling by adipocytes is still not clear. This article reviewed methods used to study cellular recycling of apoA-I and summarized the current knowledge on the mechanisms involved in apoA-I uptake by adipocytes. Since the main function of apoA-I is to mediate reverse cholesterol transport from peripheral tissues, the role of apoA-I internalization and re-secretion by adipocytes in intracellular cholesterol transport under physiological and pathological conditions were discussed. In addition, findings on the correlation between apoA-I recycling and obesity were discussed. Finally, it was proposed that during intracellular transport, apoA-I-protein complex may acquire cargoes other than lipids and deliver regulatory information when they were resecreted into the plasma. Although apoA-I recycling by adipocytes is still an unsolved mystery, it's likely that it is more than a redundant pathway especially under pathological conditions.

  12. Stages of Small Intestine Cancer

    MedlinePlus

    ... Health Professional Small Intestine Cancer Treatment Research Small Intestine Cancer Treatment (PDQ®)–Patient Version General Information About Small Intestine Cancer Go to Health Professional Version Key Points ...

  13. 78 FR 11745 - Small Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-20

    ... / Wednesday, February 20, 2013 / Rules and Regulations#0;#0; ] SMALL BUSINESS ADMINISTRATION 13 CFR Part 121 RIN 3245-AG46 Small Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small Business Technology Transfer (STTR) Program; Correction AGENCY: U.S. Small Business...

  14. 77 FR 30227 - Small Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-22

    ... BUSINESS ADMINISTRATION 13 CFR Part 121 Small Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small Business Technology Transfer (STTR) Program AGENCY: U.S. Small Business... to amend its regulations governing size and eligibility for the Small Business Innovation...

  15. Isolation and function analysis of apolipoprotein A-I gene response to virus infection in grouper.

    PubMed

    Wei, Jingguang; Gao, Pin; Zhang, Ping; Guo, Minglan; Xu, Meng; Wei, Shina; Yan, Yang; Qin, Qiwei

    2015-04-01

    Apolipoproteins, synthesized mainly in liver and intestine and bounded to lipids, play important roles in lipid transport and uptake through the circulation system. In this study, an apolipoprotein A-I gene homologue was cloned from orange-spotted grouper Epinephelus coioides (designed as Ec-ApoA-I) by rapid amplification of cDNA ends (RACE) PCR. The full-length cDNA of Ec-ApoA-I was comprised of 1278 bp with a 792 bp open reading frame (ORF) that encodes a putative protein of 264 amino acids. Quantitative real-time PCR (qPCR) analysis revealed that Ec-ApoA-I was abundant in liver and intestine, and the expression in liver was significantly (P < 0.01) up-regulated after the stimulation of LPS, Poly(I:C), Vibrio alginolyticus, and Singapore grouper iridovirus (SGIV). Recombinant Ec-ApoA-I (rEc-ApoA-I) was produced in Escherichia coli BL21 (DE3) expression system exhibited bacteriolyticactivity against Microcococcus lysodeikticus and Aeromonas hydrophila. Intracellular localization revealed that Ec-ApoA-I distributed in both cytoplasm and nucleus, and predominantly in the cytoplasm. Overexpression of Ec-ApoA-I in grouper Brain (GB) cells could inhibit the replication of SGIV. These results together indicated that Ec-ApoA-I perhaps is involved in the responses to bacterial and viral challenge. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Small Multiples with Gaps.

    PubMed

    Meulemans, Wouter; Dykes, Jason; Slingsby, Aidan; Turkay, Cagatay; Wood, Jo

    2017-01-01

    Small multiples enable comparison by providing different views of a single data set in a dense and aligned manner. A common frame defines each view, which varies based upon values of a conditioning variable. An increasingly popular use of this technique is to project two-dimensional locations into a gridded space (e.g. grid maps), using the underlying distribution both as the conditioning variable and to determine the grid layout. Using whitespace in this layout has the potential to carry information, especially in a geographic context. Yet, the effects of doing so on the spatial properties of the original units are not understood. We explore the design space offered by such small multiples with gaps. We do so by constructing a comprehensive suite of metrics that capture properties of the layout used to arrange the small multiples for comparison (e.g. compactness and alignment) and the preservation of the original data (e.g. distance, topology and shape). We study these metrics in geographic data sets with varying properties and numbers of gaps. We use simulated annealing to optimize for each metric and measure the effects on the others. To explore these effects systematically, we take a new approach, developing a system to visualize this design space using a set of interactive matrices. We find that adding small amounts of whitespace to small multiple arrays improves some of the characteristics of 2D layouts, such as shape, distance and direction. This comes at the cost of other metrics, such as the retention of topology. Effects vary according to the input maps, with degree of variation in size of input regions found to be a factor. Optima exist for particular metrics in many cases, but at different amounts of whitespace for different maps. We suggest multiple metrics be used in optimized layouts, finding topology to be a primary factor in existing manually-crafted solutions, followed by a trade-off between shape and displacement. But the rich range of possible

  17. Small reentry vehicles

    NASA Astrophysics Data System (ADS)

    Sudmeijer, K. J.

    1987-12-01

    The design and potential applications of a small modular unguided reentry vehicle (SMURV) being developed for ESA are discussed. The first studies of the SMURV concept in the Spacemail program (for transporting small payloads from the Space Shuttle to earth) are recalled; the steps in a typical Spacemail operation are listed and briefly characterized; and the smaller version of SMURV (40 kg instead of 120 kg) developed for a Space Station Spacemail project (requiring 1000-1500 SMURVs) is described. This SMURV configuration comprises a detachable propulsion module and a reentry module (containing the parachute system and the recovery module). Consideration is given to a SMURV-type vehicle to return microgravity processing samples from the ESA Interim Flight Opportunity spacecraft, the technological challenges posed by SMURV design, and SMURV applications to the Comet Nucleus Sample Return and Cassini Titan Lander missions. Diagrams and drawings are provided.

  18. Aerodynamics of Small Vehicles

    NASA Astrophysics Data System (ADS)

    Mueller, Thomas J.

    In this review we describe the aerodynamic problems that must be addressed in order to design a successful small aerial vehicle. The effects of Reynolds number and aspect ratio (AR) on the design and performance of fixed-wing vehicles are described. The boundary-layer behavior on airfoils is especially important in the design of vehicles in this flight regime. The results of a number of experimental boundary-layer studies, including the influence of laminar separation bubbles, are discussed. Several examples of small unmanned aerial vehicles (UAVs) in this regime are described. Also, a brief survey of analytical models for oscillating and flapping-wing propulsion is presented. These range from the earliest examples where quasi-steady, attached flow is assumed, to those that account for the unsteady shed vortex wake as well as flow separation and aeroelastic behavior of a flapping wing. Experiments that complemented the analysis and led to the design of a successful ornithopter are also described.

  19. Small Animal Bone Biomechanics

    PubMed Central

    Vashishth, Deepak

    2008-01-01

    Animal models, in particular mice, offer the possibility of naturally achieving or genetically engineering a skeletal phenotype associated with disease and conducting destructive fracture tests on bone to determine the resulting change in bone’s mechanical properties. Several recent developments, including nano- and micro- indentation testing, microtensile and microcompressive testing, and bending tests on notched whole bone specimens, offer the possibility to mechanically probe small animal bone and investigate the effects of aging, therapeutic treatments, disease, and genetic variation. In contrast to traditional strength tests on small animal bones, fracture mechanics tests display smaller variation and therefore offer the possibility of reducing sample sizes. This article provides an analysis of what such tests measure and proposes methods to reduce errors associated with testing smaller than ideal specimens. PMID:18672104

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-11-03

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

  2. Small arms ammunition

    DOEpatents

    Huerta, Joseph

    1992-01-01

    An elongate projectile for small arms use has a single unitary mass with a hollow nose cavity defined by a sharp rigid cutting edge adapted to make initial contact with the target surface and cut therethrough. The projectile then enters the target mass in an unstable flight mode. The projectile base is substantially solid such that the nose cavity, while relatively deep, does not extend entirely through the base and the projectile center of gravity is aft of its geometric center.

  3. Small Business Innovations (Photodetector)

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Epitaxx, Inc. of Princeton, NJ, developed the Epitaxx Near Infrared Room Temperature Indium-Gallium-Arsenide (InGaAs) Photodetector based on their Goddard Space Flight Center Small Business Innovation Research (SBIR) contract work to develop a linear detector array for satellite imaging applications using InGaAs alloys that didn't need to be cooled to (difficult and expensive) cryogenic temperatures. The photodetectors can be used for remote sensing, fiber optic and laser position-sensing applications.

  4. Small Business Innovations (MISER)

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Lightwave Electronics Corporation, Mountain View, CA, developed the Series 120 and 122 non-planner diode pumped ring lasers based on a low noise ring laser with voltage tuning that they delivered to Jet Propulsion Laboratory under a Small Business Innovation Research (SBIR) contract. The voltage tuning feature allows "phase-locking" the lasers, making them "electronic," similar to radio and microwave electronic oscillators. The Series 120 and 122 can be applied to fiber sensing, coherent communications and laser radar.

  5. Small Business Innovations

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The purpose of QASE RT is to enable system analysts and software engineers to evaluate performance and reliability implications of design alternatives. The program resulted from two Small Business Innovation Research (SBIR) projects. After receiving a description of the system architecture and workload from the user, QASE RT translates the system description into simulation models and executes them. Simulation provides detailed performance evaluation. The results of the evaluations are service and response times, offered load and device utilizations and functional availability.

  6. Small Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    The smaller of two nearby companions of the Milky Way Galaxy that can be seen with the naked eye in the southern hemisphere sky and which are named after the Portuguese navigator, Ferdinand Magellan. Located in the constellation of Tucana, at a distance of about 190 000 light-years, the Small Magellanic Cloud (SMC) has an angular diameter of about three degrees, about half the apparent diameter o...

  7. Unravelling small world networks

    NASA Astrophysics Data System (ADS)

    Higham, Desmond J.

    2003-09-01

    New classes of random graphs have recently been shown to exhibit the small world phenomenon--they are clustered like regular lattices and yet have small average pathlengths like traditional random graphs. Small world behaviour has been observed in a number of real life networks, and hence these random graphs represent a useful modelling tool. In particular, Grindrod [Phys. Rev. E 66 (2002) 066702-1] has proposed a class of range dependent random graphs for modelling proteome networks in bioinformatics. A property of these graphs is that, when suitably ordered, most edges in the graph are short-range, in the sense that they connect near-neighbours, and relatively few are long-range. Grindrod also looked at an inverse problem--given a graph that is known to be an instance of a range dependent random graph, but with vertices in arbitrary order, can we reorder the vertices so that the short-range/long-range connectivity structure is apparent? When the graph is viewed in terms of its adjacency matrix, this becomes a problem in sparse matrix theory: find a symmetric row/column reordering that places most nonzeros close to the diagonal. Algorithms of this general nature have been proposed for other purposes, most notably for reordering to reduce fill-in and for clustering large data sets. Here, we investigate their use in the small world reordering problem. Our numerical results suggest that a spectral reordering algorithm is extremely promising, and we give some theoretical justification for this observation via the maximum likelihood principle.

  8. National Small Business Conference

    DTIC Science & Technology

    2005-06-02

    Riley Valerie King Valerie King SAS Barry Alexia Nick Uros Gerri Whaley Shirley Patterson IIS John McDonald...Front Line of Innovation Department of Defense Service-Disabled Veteran-Owned Small Business Strategic Plan Increase: 1. Number of SDVOSBs in Central ...c e - E x c e l l e n c e Changing Environment: Then, Now, and Tomorrow Strategy Peer Competitor? Middle East? Central Asia? WMD? Terror? Failed

  9. Small Business Innovations

    NASA Technical Reports Server (NTRS)

    1994-01-01

    A Small Business Innovation Research (SBIR) contract resulted in a series of commercially available lasers, which have application in fiber optic communications, difference frequency generation, fiber optic sensing and general laboratory use. Developed under a Small Business Innovation Research (SBIR) contract, the Phase Doppler Particles Analyzer is a non-disruptive, highly accurate laser-based method of determining particle size, number density, trajectory, turbulence and other information about particles passing through a measurement probe volume. The system consists of an optical transmitter and receiver, signal processor and computer with data acquisition and analysis software. A variety of systems are offered for applications including spray characterization for paint, and agricultural and other sprays. The Microsizer, a related product, is used in medical equipment manufacturing and analysis of contained flows. High frequency components and subsystems produced by Millitech Corporation are marketed for both research and commercial use. These systems, which operate in the upper portion of the millimeter wave, resulted from a number of Small Business Innovation Research (SBIR) projects. By developing very high performance mixers and multipliers, the company has advanced the state of the art in sensitive receiver technology. Components are used in receivers and transceivers for monitoring chlorine monoxides, ozone, in plasma characterization and in material properties characterization.

  10. Astronomy with Small Telescopes

    NASA Astrophysics Data System (ADS)

    Paczynski, Bohdan

    2006-06-01

    While there are more than a dozen telescopes larger than 10 meters there is plenty of interesting astronomy which can be done with much smaller instruments. Notice that the existing SDSS, and the future PanSTARRS and LSST saturate at 15 mag. An example of interesting science is provided with ASAS (All Sky Automated Survey) which used aperture of 7 cm to discover over 50,000 variable stars brighter than 14 mag, covering almost 3/4 of the sky. Most of these are new discoveries.ASAS like instruments are most likely more efficient in a search for afterglows following gamma-ray bursts (GRB) than CFHT and its Megacam. In fact it should be possible to detect the afterglows without a GRB trigger by imaging all visible sky every 15 minutes down to 16 mag using a number of ASAS-like instruments.Another example of small instruments being essential, is their ability to detect 'killer asteroids' prior to their impact. It will take a number of small instruments, somewhat more powerful than ASAS, to detect boulders as small as 10 - 20 meters at a distance of several days prior to their impact. This will provide time to evacuate a region in case of Tunguska-like event, or to provide news of a spectacular but harmless event in case of a more modest impact.

  11. Small Angle Neutron Scattering

    SciTech Connect

    Urban, Volker S

    2012-01-01

    Small Angle Neutron Scattering (SANS) probes structural details at the nanometer scale in a non-destructive way. This article gives an introduction to scientists who have no prior small-angle scattering knowledge, but who seek a technique that allows elucidating structural information in challenging situations that thwart approaches by other methods. SANS is applicable to a wide variety of materials including metals and alloys, ceramics, concrete, glasses, polymers, composites and biological materials. Isotope and magnetic interactions provide unique methods for labeling and contrast variation to highlight specific structural features of interest. In situ studies of a material s responses to temperature, pressure, shear, magnetic and electric fields, etc., are feasible as a result of the high penetrating power of neutrons. SANS provides statistical information on significant structural features averaged over the probed sample volume, and one can use SANS to quantify with high precision the structural details that are observed, for example, in electron microscopy. Neutron scattering is non-destructive; there is no need to cut specimens into thin sections, and neutrons penetrate deeply, providing information on the bulk material, free from surface effects. The basic principles of a SANS experiment are fairly simple, but the measurement, analysis and interpretation of small angle scattering data involves theoretical concepts that are unique to the technique and that are not widely known. This article includes a concise description of the basics, as well as practical know-how that is essential for a successful SANS experiment.

  12. Homocysteine is a determinant of ApoA-I and both are associated with ankle brachial index, in an ambulatory elderly population.

    PubMed

    Guéant-Rodriguez, Rosa Maria; Spada, Rosario; Moreno-Garcia, Maira; Anello, Guido; Bosco, Paolo; Lagrost, Laurent; Romano, Antonino; Elia, Maurizio; Guéant, Jean-Louis

    2011-02-01

    The ankle brachial index (ABI) is an indicator of lower extremity peripheral arterial disease (PAD) and a predictor of atherothrombosis. ApoA-I and HDL are associated with PAD, in humans. Homocysteine influences the liver expression of ApoA-I and decreases its blood level and HDL in genetic mice models. We aimed therefore to evaluate whether homocysteine and its nutritional determinants, folate and vitamin B12 are associated with ABI by influencing HDL metabolism, in an ambulatory elderly population. 667 elderly volunteers from rural Sicily were assessed for ABI, homocysteine and its determinants, lipid markers and other predictors of PAD. HDL size was assessed in 15 sera in upper and lower quartiles of Hcy distribution. In multivariate analysis, ApoA-I and homocysteine were two predictors of ABI (β-coefficient = 2.86, P<0.004 and β-coefficient = -3.41, P<0.001, respectively). Homocysteine correlated negatively with ApoA-I (R = -0.147, P<0.001) and with HDL-Cholesterol (R = -0.113, P = 0.003). The associations of homocysteine, vitamin B12 and methylmalonic acid with ApoA-I and HDL2a particles and that of homocysteine with increased small size HDL3c suggested mechanisms related with impaired synthesis of ApoA-I and HDL and abnormal maturation of HDL particles. The influence of homocysteine on ApoA-I and HDL metabolism provides new insights on its role on vascular diseases, at a cross-point between atherosclerosis and atherothrombosis. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Dimyristoylphosphatidylcholine/C16:0-ceramide binary liposomes studied by differential scanning calorimetry and wide- and small-angle x-ray scattering.

    PubMed Central

    Holopainen, J M; Lemmich, J; Richter, F; Mouritsen, O G; Rapp, G; Kinnunen, P K

    2000-01-01

    Ceramide has recently been established as a central messenger in the signaling cascades controlling cell behavior. Physicochemical studies have revealed a strong tendency of this lipid toward phase separation in mixtures with phosphatidylcholines. The thermal phase behavior and structure of fully hydrated binary membranes composed of dimyristoylphosphatidylcholine (DMPC) and N-palmitoyl-ceramide (C16:0-ceramide, up to a mole fraction X(cer) = 0.35) were resolved in further detail by high-sensitivity differential scanning calorimetry (DSC) and x-ray diffraction. Both methods reveal very strong hysteresis in the thermal phase behavior of ceramide-containing membranes. A partial phase diagram was constructed based on results from a combination of these two methods. DSC heating scans show that with increased X(cer) the pretransition temperature T(p) first increases, whereafter at X(cer) > 0.06 it can no longer be resolved. The main transition enthalpy DeltaH remains practically unaltered while its width increases significantly, and the upper phase boundary temperature of the mixture shifts to approximately 63 degrees C at X(cer) = 0.30. Upon cooling, profound phase separation is evident, and for all of the studied compositions there is an endotherm in the region close to the T(m) for DMPC. At X(cer) >/= 0.03 a second endotherm is evident at higher temperatures, starting at 32.1 degrees C and reaching 54.6 degrees C at X(cer) = 0.30. X-ray small-angle reflection heating scans reveal a lamellar phase within the temperature range of 15-60 degrees C, regardless of composition. The pretransition is observed up to X(cer) < 0.18, together with an increase in T(p). In the gel phase the lamellar repeat distance d increases from approximately 61 A at X(cer) = 0. 03, to 67 A at X(cer) = 0.35. In the fluid phase increasing X(cer) from 0.06 to 0.35 augments d from 61 A to 64 A. An L(beta')/L(alpha) (ripple/fluid) phase coexistence region is observed at high temperatures (from 31 to

  14. 22 CFR 214.3 - A.I.D. Advisory Committee Management Officer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false A.I.D. Advisory Committee Management Officer. 214.3 Section 214.3 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADVISORY COMMITTEE MANAGEMENT General § 214.3 A.I.D. Advisory Committee Management Officer. The Advisory Committee Management...

  15. 22 CFR 214.3 - A.I.D. Advisory Committee Management Officer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false A.I.D. Advisory Committee Management Officer. 214.3 Section 214.3 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADVISORY COMMITTEE MANAGEMENT General § 214.3 A.I.D. Advisory Committee Management Officer. The Advisory Committee Management...

  16. Apolipoprotein B and A-I ratio predicts severe acute pancreatitis.

    PubMed

    Huh, Ji Hye; Jung, Saehyun; Cho, Seung Kook; Lee, Kyong Joo; Kim, Jae Woo

    2017-07-05

    Severe acute pancreatitis (SAP) has considerable mortality and morbidity rates. Although many indices have been developed to classify the severity of acute pancreatitis (AP), an optimal method for predicting SAP has not been identified. The ratio of apolipoprotein B to A-I (apoB/A-I) is associated with metabolic syndrome and inflammatory status. This study investigated the association between severity of AP and serum apoB/A-I ratio. Patients with AP were prospectively enrolled at Yonsei University Wonju College of Medicine from March 2015 to August 2016. The severity of AP was assessed according to the revised Atlanta classification criteria (Atlanta 2012). Of 191 patients with AP, 134 (70.2%) had mild AP, 42 (22%) had moderately severe AP, and 15 (7.9%) had SAP; apoB/A-I ratio was highest in patients with SAP (P = 0.001). The apoB/A-I ratio was positively correlated with Atlanta classification, computed tomography severity index, and Bedside index for severity of AP. The apoB/A-I ratio showed the highest predictive value for SAP in patients with AP compared with apolipoprotein B or apolipoprotein A-I alone. Serum apoB/A-I ratio appears to have value for predicting SAP in patients with AP. This article is protected by copyright. All rights reserved.

  17. 22 CFR 214.3 - A.I.D. Advisory Committee Management Officer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false A.I.D. Advisory Committee Management Officer. 214.3 Section 214.3 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADVISORY COMMITTEE MANAGEMENT General § 214.3 A.I.D. Advisory Committee Management Officer. The Advisory Committee Management...

  18. 22 CFR 214.3 - A.I.D. Advisory Committee Management Officer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false A.I.D. Advisory Committee Management Officer. 214.3 Section 214.3 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADVISORY COMMITTEE MANAGEMENT General § 214.3 A.I.D. Advisory Committee Management Officer. The Advisory Committee Management...

  19. High-Throughput Analysis Identifying Drugs That Regulate Apolipoprotein A-I Synthesis.

    PubMed

    Haas, Michael J; Onstead-Haas, Luisa; Kurban, William; Shah, Harshit; Plazarte, Monica; Chamseddin, Ayham; Mooradian, Arshag D

    2017-07-25

    Apolipoprotein A-I (apo A-I) is the primary antiatherogenic protein in high-density lipoprotein (HDL). Despite the controversy as to the clinical effectiveness of raising HDL, the search is ongoing for safe and effective drugs that increase HDL and apo A-I levels. To identify novel compounds that can increase hepatic apo A-I production, two drug libraries were screened. The NIH clinical collection (NCC) and the NIH clinical collection 2 (NCC2) were purchased from Evotec (San Francisco, CA). The NCC library contains 446 compounds and the NCC2 library contains 281 compounds, all dissolved in dimethylsulfoxide at a concentration of 10 mM. Hepatoma-derived cells (HepG2) and primary hepatocytes in culture were treated with various compounds for 24 h and apo A-I in media samples was measured by enzyme immunoassay. Samples with significant changes in apo A-I concentrations were retested in independent experiments by Western blot analysis to confirm the immunoassay findings. Of a total of 727 compounds screened at a concentration of 50 μM, 15 compounds increased hepatic apo A-I production by 35%-54%, and 9 compounds lowered hepatic apo A-I concentrations in the culture media by 25%-52%. Future trials should explore the clinical effectiveness of these agents when standard doses of these drugs are used in humans.

  20. Serum apolipoprotein A-I is a novel prognostic indicator for non-metastatic nasopharyngeal carcinoma.

    PubMed

    Luo, Xiao-Lin; Zhong, Guang-Zheng; Hu, Li-Yang; Chen, Jie; Liang, Ying; Chen, Qiu-Yan; Liu, Qing; Rao, Hui-Lan; Chen, Kai-Lin; Cai, Qing-Qing

    2015-12-22

    We investigated the value of pretreatment serum apolipoprotein A-I (ApoA-I) in complementing TNM staging in the prognosis of non-metastatic nasopharyngeal carcinoma (NPC). We retrospectively reviewed 1196 newly diagnosed patients with non-metastatic NPC. Disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were compared according to serum ApoA-I level. Multivariate analysis was performed to assess the prognostic value of serum ApoA-I. The 5-year DSS, DMFS, and LRFS rates for patients with elevated or decreased serum ApoA-I were 81.3% versus 69.3% (P < 0.001), 83.4% versus 67.4% (P < 0.001), and 80.9% versus 67.3% (P < 0.001), respectively. ApoA-I ≥ 1.025 g/L was an independent prognostic factor for superior DSS, DMFS, and LRFS in multivariate analysis. After stratification by clinical stage, serum ApoA-I remained a clinically and statistically significant predictor of prognosis. Our data suggest that the level of ApoA-I at diagnosis is a novel independent prognostic marker that could complement clinical staging for risk definition in non-metastatic NPC.

  1. 22 CFR 214.3 - A.I.D. Advisory Committee Management Officer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false A.I.D. Advisory Committee Management Officer. 214.3 Section 214.3 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADVISORY COMMITTEE MANAGEMENT General § 214.3 A.I.D. Advisory Committee Management Officer. The Advisory Committee Management...

  2. Matrix metalloproteinase 8 degrades apolipoprotein A-I and reduces its cholesterol efflux capacity.

    PubMed

    Salminen, Aino; Åström, Pirjo; Metso, Jari; Soliymani, Rabah; Salo, Tuula; Jauhiainen, Matti; Pussinen, Pirkko J; Sorsa, Timo

    2015-04-01

    Various cell types in atherosclerotic lesions express matrix metalloproteinase (MMP)-8. We investigated whether MMP-8 affects the structure and antiatherogenic function of apolipoprotein (apo) A-I, the main protein component of HDL particles. Furthermore, we studied serum lipid profiles and cholesterol efflux capacity in MMP-8-deficient mouse model. Incubation of apoA-I (28 kDa) with activated MMP-8 yielded 22 kDa and 25 kDa apoA-I fragments. Mass spectrometric analyses revealed that apoA-I was cleaved at its carboxyl-terminal part. Treatment of apoA-I and HDL with MMP-8 resulted in significant reduction (up to 84%, P < 0.001) in their ability to facilitate cholesterol efflux from cholesterol-loaded THP-1 macrophages. The cleavage of apoA-I by MMP-8 and the reduction in its cholesterol efflux capacity was inhibited by doxycycline. MMP-8-deficient mice had significantly lower serum triglyceride (TG) levels (P = 0.003) and larger HDL particles compared with wild-type (WT) mice. However, no differences were observed in the apoA-I levels or serum cholesterol efflux capacities between the mouse groups. Proteolytic modification of apoA-I by MMP-8 may impair the first steps of reverse cholesterol transport, leading to increased accumulation of cholesterol in the vessel walls. Eventually, inhibition of MMPs by doxycycline may reduce the risk for atherosclerotic vascular diseases.

  3. Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency

    USDA-ARS?s Scientific Manuscript database

    Our aim was to characterize HDL subspecies and fat-soluble vitamin levels in a kindred with familial apolipoprotein A-I (apoA-I) deficiency. Sequencing of the APOA1 gene revealed a nonsense mutation at codon 22, Q[22]X, with two documented homozygotes, eight heterozygotes, and two normal subjects in...

  4. Human Apolipoprotein A-I Natural Variants: Molecular Mechanisms Underlying Amyloidogenic Propensity

    PubMed Central

    Ramella, Nahuel A.; Schinella, Guillermo R.; Ferreira, Sergio T.; Prieto, Eduardo D.; Vela, María E.; Ríos, José Luis

    2012-01-01

    Human apolipoprotein A-I (apoA-I)-derived amyloidosis can present with either wild-type (Wt) protein deposits in atherosclerotic plaques or as a hereditary form in which apoA-I variants deposit causing multiple organ failure. More than 15 single amino acid replacement amyloidogenic apoA-I variants have been described, but the molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here, we have investigated by fluorescence and biochemical approaches the stabilities and propensities to aggregate of two disease-associated apoA-I variants, apoA-IGly26Arg, associated with polyneuropathy and kidney dysfunction, and apoA-ILys107-0, implicated in amyloidosis in severe atherosclerosis. Results showed that both variants share common structural properties including decreased stability compared to Wt apoA-I and a more flexible structure that gives rise to formation of partially folded states. Interestingly, however, distinct features appear to determine their pathogenic mechanisms. ApoA-ILys107-0 has an increased propensity to aggregate at physiological pH and in a pro-inflammatory microenvironment than Wt apoA-I, whereas apoA-IGly26Arg elicited macrophage activation, thus stimulating local chronic inflammation. Our results strongly suggest that some natural mutations in apoA-I variants elicit protein tendency to aggregate, but in addition the specific interaction of different variants with macrophages may contribute to cellular stress and toxicity in hereditary amyloidosis. PMID:22952757

  5. 22 CFR 204.33 - A.I.D. approval of acceleration of notes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false A.I.D. approval of acceleration of notes. 204.33 Section 204.33 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Covenants § 204.33 A.I.D. approval of acceleration of notes. Without the...

  6. 22 CFR 204.33 - A.I.D. approval of acceleration of notes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false A.I.D. approval of acceleration of notes. 204.33 Section 204.33 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Covenants § 204.33 A.I.D. approval of acceleration of notes. Without the...

  7. 22 CFR 204.33 - A.I.D. approval of acceleration of notes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false A.I.D. approval of acceleration of notes. 204.33 Section 204.33 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Covenants § 204.33 A.I.D. approval of acceleration of notes. Without the...

  8. 22 CFR 204.33 - A.I.D. approval of acceleration of notes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false A.I.D. approval of acceleration of notes. 204.33 Section 204.33 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Covenants § 204.33 A.I.D. approval of acceleration of notes. Without the...

  9. 22 CFR 204.33 - A.I.D. approval of acceleration of notes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false A.I.D. approval of acceleration of notes. 204.33 Section 204.33 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Covenants § 204.33 A.I.D. approval of acceleration of notes. Without the...

  10. Regulation of the promoter of rat apolipoprotein A-I gene in cultured cells

    SciTech Connect

    Chao, Y.; Pan, T.; Wu, T.; Hao, Q.; Yamin, T.; Kroon, P.A.

    1987-05-01

    In order to study the regulation of the promoter of apolipoprotein (apo) A-I gene, they joined the 5' end of rat apo A-I gene (1.9 Kb) to the coding region of bacterial chloramphenicol acetyltransferase (CAT) gene. The chimeric gene produced high levels of CAT activity in both mouse L cells and Hep G2 cells in transient expression assays. Ethanol increased the levels of rat apo A-I promoter activity in both cells. However, dexamethasone increased rat apo A-I promoter activity only in Hep G2 cells. Similar results were obtained in stable expression cell lines. Nucleotide deletion experiments showed DNA sequences between -149 and -469 base pairs upstream from the rat apo A-I transcription site are required for the high level of expression and that the regulatory sequences are located further upstream. These data demonstrated that the 5' end of rat apo A-I gene contains sequences which are responsible for the regulation of apo A-I expression by ethanol and dexamethasone and that the expression and regulation of rat apo A-I promoter are cell specific.

  11. Dietary Strategies and Novel Pharmaceutical Approaches Targeting Serum ApoA-I Metabolism: A Systematic Overview

    PubMed Central

    Smolders, Lotte; Plat, Jogchum

    2017-01-01

    The incidence of CHD is still increasing, which underscores the need for new preventive and therapeutic approaches to decrease CHD risk. In this respect, increasing apoA-I concentrations may be a promising approach, especially through increasing apoA-I synthesis. This review first provides insight into current knowledge on apoA-I production, clearance, and degradation, followed by a systematic review of dietary and novel pharmacological approaches to target apoA-I metabolism. For this, a systematic search was performed to identify randomized controlled intervention studies that examined effects of whole foods and (non)nutrients on apoA-I metabolism. In addition, novel pharmacological approaches were searched for, which were specifically developed to target apoA-I metabolism. We conclude that both dietary components and pharmacological approaches can be used to increase apoA-I concentrations or functionality. For the dietary components in particular, more knowledge about the underlying mechanisms is necessary, as increasing apoA-I per se does not necessarily translate into a reduced CHD risk. PMID:28695008

  12. Managing Small-Group Learning.

    ERIC Educational Resources Information Center

    Reid, Jo-Anne

    Students working together in small groups are a familiar scene in Australian elementary schools. But why are small groups used, and who benefits from their use? This book puts the case for small-group organization in the light of contemporary educational theory. In doing so, the book guides the teacher taking the first steps towards small-group…

  13. The Small Mars System

    NASA Astrophysics Data System (ADS)

    Fantino, E.; Grassi, M.; Pasolini, P.; Causa, F.; Molfese, C.; Aurigemma, R.; Cimminiello, N.; de la Torre, D.; Dell'Aversana, P.; Esposito, F.; Gramiccia, L.; Paudice, F.; Punzo, F.; Roma, I.; Savino, R.; Zuppardi, G.

    2017-08-01

    The Small Mars System is a proposed mission to Mars. Funded by the European Space Agency, the project has successfully completed Phase 0. The contractor is ALI S.c.a.r.l., and the study team includes the University of Naples ;Federico II;, the Astronomical Observatory of Capodimonte and the Space Studies Institute of Catalonia. The objectives of the mission are both technological and scientific, and will be achieved by delivering a small Mars lander carrying a dust particle analyser and an aerial drone. The former shall perform in situ measurements of the size distribution and abundance of dust particles suspended in the Martian atmosphere, whereas the latter shall demonstrate low-altitude flight in the rarefied planetary environment. The mission-enabling technology is an innovative umbrella-like heat shield, known as IRENE, developed and patented by ALI. The mission is also a technological demonstration of the shield in the upper atmosphere of Mars. The core characteristics of SMS are the low cost (120 M€) and the small size (320 kg of wet mass at launch, 110 kg at landing), features which stand out with respect to previous Mars landers. To comply with them is extremely challenging at all levels, and sets strict requirements on the choice of the materials, the sizing of payloads and subsystems, their arrangement inside the spacecraft and the launcher's selection. In this contribution, the mission and system concept and design are illustrated and discussed. Special emphasis is given to the innovative features and to the challenges faced in the development of the work.

  14. Eccentricity of small exoplanets

    NASA Astrophysics Data System (ADS)

    Van Eylen, Vincent; Albrecht, Simon

    2015-12-01

    Solar system planets move on almost circular orbits. In strong contrast, many massive gas giant exoplanets travel on highly elliptical orbits, whereas the shape of the orbits of smaller, more terrestrial, exoplanets remained largely elusive. This is because the stellar radial velocity caused by these small planets is extremely challenging to measure. Knowing the eccentricity distribution in systems of small planets would be important as it holds information about the planet's formation and evolution. Furthermore the location of the habitable zone depends on eccentricity, and eccentricity also influences occurrence rates inferred for these planets because planets on circular orbits are less likely to transit. We make these eccentricity measurements of small planets using photometry from the Kepler satellite and utilizing a method relying on Kepler's second law, which relates the duration of a planetary transit to its orbital eccentricity, if the stellar density is known.I present a sample of 28 multi-planet systems with precise asteroseismic density measurements, which host 74 planets with an average radius of 2.6 R_earth. We find that the eccentricity of planets in these systems is low and can be described by a Rayleigh distribution with sigma = 0.049 +- 0.013. This is in full agreement with solar system eccentricities, but in contrast to the eccentricity distributions previously derived for exoplanets from radial velocity studies. I further report the first results on the eccentricities of over 50 Kepler single-planet systems, and compare them with the multi-planet systems. I close the talk by showing how transit durations help distinguish between false positives and true planets, and present six new planets.

  15. Correlations Between Serum Apolipoprotein A-I and Formation of Vocal Cord Polyp.

    PubMed

    Zhang, Hui-Ping; Zhang, Rong

    2017-05-01

    This study aims to investigate the correlations between serum apolipoprotein A-I (ApoA-I) and the formation of vocal cord polyps (VCPs). This study used the nonmatched case-control study method. The serum total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, ApoA-I, apolipoprotein B (ApoB), and ApoA-I/ApoB levels of 89 VCP patients and 87 normal volunteers were compared. Additionally, such VCP-related factors as excessive vocal use, vocal abuse, smoking, drinking, and the size of VCPs were analyzed. The two groups did not significantly differ with regard to triglyceride, low-density lipoprotein cholesterol, ApoB, and ApoA-I/ApoB levels (P > 0.05), whereas they did significantly differ with regard to TC, HDL-C, and ApoA-I levels (P < 0.05) according to independent t tests. Logistic regression analysis showed that excessive vocal use and vocal abuse were risk factors for VCPs (P < 0.05), with odds ratio values of 5.675 and 12.781, respectively. The ApoA-I level was negatively associated with VCPs (P < 0.05), with an odds ratio of 0.511; however, TC and HDL-C were not associated with the formation of VCPs (P > 0.05). The size of VCPs in females was negatively correlated with the serum ApoA-I level (r = -0.349, P = 0.032), whereas that in males was not (P > 0.05). As the serum ApoA-I level was negatively correlated with the formation of VCPs, ApoA-I may reduce the risk of VCPs. These findings may facilitate the prevention and treatment of VCPs. Copyright © 2017. Published by Elsevier Inc.

  16. Anti-apolipoprotein A-I antibodies and paraoxonase 1 activity in Systemic Lupus Erythematosus

    PubMed Central

    Ahmed, Mohammed Mahmoud; Elserougy, Eman Mahmoud; Al-Gazzar, Iman Ibrahim; Fikry, Iman Mohamed; Habib, Dawoud Fakhry; Younes, Khaled Mohamed; Salem, Neveen Abd El-hameed

    2013-01-01

    Systemic lupus erythematosus (SLE) patients have an increased risk of atherosclerosis. Identification of at-risk patients and the pathogenesis of atherosclerosis in SLE remain elusive. Paraoxonase 1 (PON1) and anti-apolipoprotein A-I antibody (anti-Apo A-I) appear to have a potential role in premature atherosclerosis in SLE. The aim of this work was to study PON1 activity and anti-Apo A-I antibody in SLE female patients and to demonstrate their relations to disease activity as well as disease related damage. Forty SLE female patients and 40 apparently healthy volunteers were included. Anti-Apo A-I antibodies levels and PON1 activity levels were assessed. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and systemic Lupus International Collaboration Clinics (SLICC)/American College of Rheumatology (ACR) damage index were preformed in all patients. Compared with controls, SLE patients showed significantly lower PON1 activity and significantly higher titers of anti-Apo A-I. Anti-Apo A-I antibody titers correlated inversely with PON1 activity. Elevated titers of anti-Apo A-I antibody and reduced PON activity were related to increased SLEDAI and (SLICC/ACR) damage index scores. We concluded that there is decreased PON1 activity and formation of anti-Apo A-I antibodies in female patients with SLE. SLE-disease activity assessed by SLEDAI and SLE disease related organ damage assessed by SLICC/ACR damage index are negatively correlated with PON1 activity and positively correlated with anti-Apo A-I antibodies. PON1 activity and anti-Apo A-I antibodies might be involved in the pathogenesis of atherosclerosis in SLE patients. PMID:26622215

  17. Overexpression of apolipoprotein A-I alleviates endoplasmic reticulum stress in hepatocytes.

    PubMed

    Guo, Qing; Zhang, Can; Wang, Yutong

    2017-06-02

    Abnormal lipid metabolism may contribute to an increase in endoplasmic reticulum (ER) stress, resulting in the pathogenesis of non-alcoholic steatohepatitis. Apolipoprotein A-I (apoA-I) accepts cellular free cholesterol and phospholipids transported by ATP-binding cassette transporter A1 to generate nascent high density lipoprotein particles. Previous studies have revealed that the overexpression of apoA-I alleviated hepatic lipid levels by modifying lipid transport. Here, we examined the effects of apoA-I overexpression on ER stress and genes involved in lipogenesis in both HepG2 cells and mouse hepatocytes. Human apoA-I was overexpressed in HepG2 hepatocytes, which were then treated with 2 μg/mL tunicamycin or 500 μM palmitic acid. Eight-week-old male apoA-I transgenic or C57BL/6 wild-type mice were intraperitoneally injected with 1 mg/kg body weight tunicamycin or with saline. At 48 h after injecting, blood and liver samples were collected. The overexpression of apoA-I in the models above resulted in decreased protein levels of ER stress makers and lipogenic gene products, including sterol regulatory element binding protein 1, fatty acid synthase, and acetyl-CoA carboxylase 1. In addition, the cellular levels of triglycerides and free cholesterol also decreased. Some of gene products which are related to ER stress-associated apoptosis were also affected by apoA-I overexpression. These results suggested that apoA-I overexpression could reduce steatosis by decreasing lipid levels and by suppressing ER stress and lipogenesis in hepatocytes. ApoA-I expression could significantly reduce hepatic ER stress and lipogenesis in hepatocytes.

  18. Small circuits for cryptography.

    SciTech Connect

    Torgerson, Mark Dolan; Draelos, Timothy John; Schroeppel, Richard Crabtree; Miller, Russell D.; Anderson, William Erik

    2005-10-01

    This report examines a number of hardware circuit design issues associated with implementing certain functions in FPGA and ASIC technologies. Here we show circuit designs for AES and SHA-1 that have an extremely small hardware footprint, yet show reasonably good performance characteristics as compared to the state of the art designs found in the literature. Our AES performance numbers are fueled by an optimized composite field S-box design for the Stratix chipset. Our SHA-1 designs use register packing and feedback functionalities of the Stratix LE, which reduce the logic element usage by as much as 72% as compared to other SHA-1 designs.

  19. Rapid small lot manufacturing

    SciTech Connect

    Harrigan, R.W.

    1998-05-09

    The direct connection of information, captured in forms such as CAD databases, to the factory floor is enabling a revolution in manufacturing. Rapid response to very dynamic market conditions is becoming the norm rather than the exception. In order to provide economical rapid fabrication of small numbers of variable products, one must design with manufacturing constraints in mind. In addition, flexible manufacturing systems must be programmed automatically to reduce the time for product change over in the factory and eliminate human errors. Sensor based machine control is needed to adapt idealized, model based machine programs to uncontrolled variables such as the condition of raw materials and fabrication tolerances.

  20. Small Cell Lung Cancer

    PubMed Central

    Kalemkerian, Gregory P.; Akerley, Wallace; Bogner, Paul; Borghaei, Hossein; Chow, Laura QM; Downey, Robert J.; Gandhi, Leena; Ganti, Apar Kishor P.; Govindan, Ramaswamy; Grecula, John C.; Hayman, James; Heist, Rebecca Suk; Horn, Leora; Jahan, Thierry; Koczywas, Marianna; Loo, Billy W.; Merritt, Robert E.; Moran, Cesar A.; Niell, Harvey B.; O’Malley, Janis; Patel, Jyoti D.; Ready, Neal; Rudin, Charles M.; Williams, Charles C.; Gregory, Kristina; Hughes, Miranda

    2013-01-01

    Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted. PMID:23307984

  1. Small cell lung cancer.

    PubMed

    Kalemkerian, Gregory P; Akerley, Wallace; Bogner, Paul; Borghaei, Hossein; Chow, Laura Qm; Downey, Robert J; Gandhi, Leena; Ganti, Apar Kishor P; Govindan, Ramaswamy; Grecula, John C; Hayman, James; Heist, Rebecca Suk; Horn, Leora; Jahan, Thierry; Koczywas, Marianna; Loo, Billy W; Merritt, Robert E; Moran, Cesar A; Niell, Harvey B; O'Malley, Janis; Patel, Jyoti D; Ready, Neal; Rudin, Charles M; Williams, Charles C; Gregory, Kristina; Hughes, Miranda

    2013-01-01

    Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.

  2. Small Business Innovations

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The PER-Force Handcontroller was originally developed for the International Space Station under a Johnson Space Center Small Business Innovation Research (SBIR) contract. Produced by Cybernet Systems Corporation, the unit is a force-reflecting system that manipulates robots or objects by "feel." The Handcontroller moves in six degrees of freedom, with real and virtual reality forces simulated by a 3-D molecular modeling software package. It is used in molecular modeling in metallurgy applications, satellite docking research, and in research on military unmanned ground vehicles.

  3. Small Business Innovations (Cryostat)

    NASA Technical Reports Server (NTRS)

    1991-01-01

    General Pneumatics Corporation, Scottsdale, AZ, developed an anti- clogging cryostat that liquifies gases by expansion for high pressure through a nozzle to produce cryorefrigeration based on their Kennedy Space Center Small Business Innovation Research (SBIR) work to develop a Joule-Thomson (JT) expansion valve that is less susceptible to clogging by particles or condensed contaminants in the flow than a non-contaminating compressor in a closed cycle Linde-Hampson cryocooler used to generate cryogenic cooling for infrared sensors, super conductors, supercooled electronics and cryosurgery.

  4. Small satellite space operations

    NASA Technical Reports Server (NTRS)

    Reiss, Keith

    1994-01-01

    CTA Space Systems has played a premier role in the development of the 'lightsat' programs of the 80's and 90's. The high costs and development times associated with conventional LEO satellite design, fabrication, launch, and operations continue to motivate the development of new methodologies, techniques, and generally low cost and less stringently regulated satellites. These spacecraft employ low power 'lightsat' communications (versus TDRSS for NASA's LEO's) and typically fly missions with payload/experiment suites that can succeed, for example, without heavily redundant backup systems and large infrastructures of personnel and ground support systems. Such small yet adaptable satellites are also typified by their very short contract-to-launch times (often one to two years). This paper reflects several of the methodologies and perspectives of our successful involvement in these innovative programs and suggests how they might relieve NASA's mounting pressures to reduce the cost of both the spacecraft and their companion mission operations. It focuses on the use of adaptable, sufficiently powerful yet inexpensive PC-based ground systems for wide ranging user terminal (UT) applications and master control facilities for mission operations. These systems proved themselves in successfully controlling more than two dozen USAF, USN, and ARPA satellites at CTA/SS. UT versions have linked with both GEO and LEO satellites and functioned autonomously in relay roles often in remote parts of the world. LEO applications particularly illustrate the efficacy of these concepts since a user can easily mount a lightweight antenna, usually an omni or helix with light duty rotors and PC-based drivers. A few feet of coax connected to a small transceiver module (the size of a small PC) and a serial line to an associated PC establishes a communications link and together with the PC constitute a viable ground station. Applications included geomagnetic mapping; spaceborne solid state

  5. Small clusters: aerosol precursors

    SciTech Connect

    Castleman, A.W. Jr.; Keesee, R.G.

    1983-01-01

    Studies of the structure, stability, electronic properties, and formation kinetics of small clusters provide information useful in furthering an understanding of nucleation processes, the formation and stability of collodial media, and the nature of surfaces. Using mass spectrometry, coupled with various high pressure ion clustering and molecular beam techniques, the details of the primary clustering steps leading to nucleation from the vapor are obtained by direct observation. This paper is devoted to a review of some recent results on these subjects obtained in the authors' laboratory.

  6. Small Business Innovations (Helicopters)

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The amount of engine power required for a helicopter to hover is an important, but difficult, consideration in helicopter design. The EHPIC program model produces converged, freely distorted wake geometries that generate accurate analysis of wake-induced downwash, allowing good predictions of rotor thrust and power requirements. Continuum Dynamics, Inc., the Small Business Innovation Research (SBIR) company that developed EHPIC, also produces RotorCRAFT, a program for analysis of aerodynamic loading of helicopter blades in forward flight. Both helicopter codes have been licensed to commercial manufacturers.

  7. NIF small mirror mount

    SciTech Connect

    McCarville, T

    1999-07-01

    A number of small mirror mounts have been identified that meet the stringent stability, wave front, and cleanliness standards of the NIF. These requirements are similar to those required in other performance critical optical design applications. Future design teams would conserve time and effort if recognized standards were established for mirror mount design and performance characteristics. Standards for stability, physical features, wave front distortion, and cleanliness would simplify the qualification process considerably. At this point such standards are not difficult to define, as the technical support work has been performed repeatedly by mirror mount consumers and suppliers.

  8. Small Tharsis Volcano

    NASA Technical Reports Server (NTRS)

    2004-01-01

    30 August 2004 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a small volcano located southwest of the giant volcano, Pavonis Mons, near 2.5oS, 109.4oW. Lava flows can be seen to have emanated from the summit region, which today is an irregularly-shaped collapse pit, or caldera. A blanket of dust mantles this volcano. Dust covers most martian volcanoes, none of which are young or active today. This picture covers an area about 3 km (1.9 mi) across; sunlight illuminates the scene from the left.

  9. Small Landslide in Kasei

    NASA Technical Reports Server (NTRS)

    2004-01-01

    21 February 2004 The finger-shaped lobe just right of center in this Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image is the deposit of a small landslide that came down a dark, layered slope. Landslides are common on Mars in areas of steep topography; this one is located in the Kasei Valles region near 23.9oN, 67.1oW. Sunlight illuminates the scene from the lower left; the picture covers an area 3 km (1.9 mi) wide.

  10. Small obstacle avoidance sensor.

    PubMed

    Vollmerhausen, Richard H

    2013-01-01

    This paper describes a laser ranging sensor that is suitable for applications like small unmanned aerial vehicles. The hardware consists of a diode emitter array and line-scan charge coupled devices. A structured-light technique measures ranges up to 30 meters for 64 field angles in a 90 degree field of view. Operation is eye safe, and the laser wavelength is not visible to night vision goggles. This paper describes a specific sensor design in order to illustrate performance for a given package size.

  11. Small Cube Satellite Deploy

    NASA Image and Video Library

    2013-11-19

    ISS038-E-003872 (19 Nov. 2013) --- Three nanosatellites, known as Cubesats, are deployed from a Small Satellite Orbital Deployer (SSOD) attached to the Kibo laboratory’s robotic arm at 7:10 a.m. (EST) on Nov. 19, 2013. Japan Aerospace Exploration Agency astronaut Koichi Wakata, Expedition 38 flight engineer, monitored the satellite deployment while operating the Japanese robotic arm from inside Kibo. The Cubesats were delivered to the International Space Station Aug. 9, aboard Japan’s fourth H-II Transfer Vehicle, Kounotori-4.

  12. Small Cube Satellite Deploy

    NASA Image and Video Library

    2013-11-19

    ISS038-E-003874 (19 Nov. 2013) --- Three nanosatellites, known as Cubesats, are deployed from a Small Satellite Orbital Deployer (SSOD) attached to the Kibo laboratory's robotic arm at 7:10 a.m. (EST) on Nov. 19, 2013. Japan Aerospace Exploration Agency astronaut Koichi Wakata, Expedition 38 flight engineer, monitored the satellite deployment while operating the Japanese robotic arm from inside Kibo. The Cubesats were delivered to the International Space Station Aug. 9, aboard Japan's fourth H-II Transfer Vehicle, Kounotori-4.

  13. Small Cube Satellite Deploy

    NASA Image and Video Library

    2013-11-19

    ISS038-E-003876 (19 Nov. 2013) --- Three nanosatellites, known as Cubesats, are featured in this image photographed by an Expedition 38 crew member on the International Space Station. The satellites were released outside the Kibo laboratory using a Small Satellite Orbital Deployer attached to the Japanese module's robotic arm on Nov. 19, 2013. Japan Aerospace Exploration Agency astronaut Koichi Wakata, flight engineer, monitored the satellite deployment while operating the Japanese robotic arm from inside Kibo. The Cubesats were delivered to the International Space Station Aug. 9, aboard Japan’s fourth H-II Transfer Vehicle, Kounotori-4.

  14. Small Cube Satellite Deploy

    NASA Image and Video Library

    2013-11-19

    ISS038-E-003869 (19 Nov. 2013) --- Three nanosatellites, known as Cubesats, are deployed from a Small Satellite Orbital Deployer (SSOD) attached to the Kibo laboratory’s robotic arm at 7:10 a.m. (EST) on Nov. 19, 2013. Japan Aerospace Exploration Agency astronaut Koichi Wakata, Expedition 38 flight engineer, monitored the satellite deployment while operating the Japanese robotic arm from inside Kibo. The Cubesats were delivered to the International Space Station Aug. 9, aboard Japan’s fourth H-II Transfer Vehicle, Kounotori-4.

  15. Small Cube Satellite Deploy

    NASA Image and Video Library

    2013-11-19

    ISS038-E-003871 (19 Nov. 2013) --- Three nanosatellites, known as Cubesats, are deployed from a Small Satellite Orbital Deployer (SSOD) attached to the Kibo laboratory’s robotic arm at 7:10 a.m. (EST) on Nov. 19, 2013. Japan Aerospace Exploration Agency astronaut Koichi Wakata, Expedition 38 flight engineer, monitored the satellite deployment while operating the Japanese robotic arm from inside Kibo. The Cubesats were delivered to the International Space Station Aug. 9, aboard Japan’s fourth H-II Transfer Vehicle, Kounotori-4.

  16. Three small deployed satellites

    NASA Image and Video Library

    2012-10-04

    ISS033-E-009282 (4 Oct. 2012) --- Several tiny satellites are featured in this image photographed by an Expedition 33 crew member on the International Space Station. The satellites were released outside the Kibo laboratory using a Small Satellite Orbital Deployer attached to the Japanese module’s robotic arm on Oct. 4, 2012. Japan Aerospace Exploration Agency astronaut Aki Hoshide, flight engineer, set up the satellite deployment gear inside the lab and placed it in the Kibo airlock. The Japanese robotic arm then grappled the deployment system and its satellites from the airlock for deployment. Earth’s horizon and the blackness of space provide the backdrop for the scene.

  17. Small Cube Satellite Deploy

    NASA Image and Video Library

    2013-11-19

    ISS038-E-003870 (19 Nov. 2013) --- Three nanosatellites, known as Cubesats, are deployed from a Small Satellite Orbital Deployer (SSOD) attached to the Kibo laboratory’s robotic arm at 7:10 a.m. (EST) on Nov. 19, 2013. Japan Aerospace Exploration Agency astronaut Koichi Wakata, Expedition 38 flight engineer, monitored the satellite deployment while operating the Japanese robotic arm from inside Kibo. The Cubesats were delivered to the International Space Station Aug. 9, aboard Japan’s fourth H-II Transfer Vehicle, Kounotori-4.

  18. Small modulation ellipsometry

    NASA Technical Reports Server (NTRS)

    Ducharme, Stephen P. (Inventor); El Hajj, Hassanayn M. (Inventor); Johs, Blaine D. (Inventor); Woollam, John A. (Inventor)

    1995-01-01

    In an ellipsometer, a phase-modulated, polarized light beam is applied to a sample, electrical signals are obtained representing the orthogonal planes of polarization of the light after it has interacted with the sample and the constants of the sample are calculated from the two resulting electrical signals. The phase modulation is sufficiently small so that the calibration errors are negligible. For this purpose, the phase modulator phase modulates the light within a range of no more than ten degrees modulations peak to peak. The two electrical signals are expanded by Fourier analysis and the coefficients thereof utilized to calculate psi and delta.

  19. Small Landslide in Kasei

    NASA Technical Reports Server (NTRS)

    2004-01-01

    21 February 2004 The finger-shaped lobe just right of center in this Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image is the deposit of a small landslide that came down a dark, layered slope. Landslides are common on Mars in areas of steep topography; this one is located in the Kasei Valles region near 23.9oN, 67.1oW. Sunlight illuminates the scene from the lower left; the picture covers an area 3 km (1.9 mi) wide.

  20. SmallSat Lab

    DTIC Science & Technology

    2014-03-05

    CubeSat. Mr. Alvarez worked with four students on the PCB layout for the solar panels and the construction of the 6U CubeSat mockup . Support for Mr...Hull and Mr. Alvarez was $49k including fringe benefits. !! Purchases: During this time period a license for MatLab software and the Princeton...Satellite ToolBox was purchased using funds from this award. This software adds tremendous capability to the SmallSat Lab by enabling students to analyze

  1. Structure of gel phase DMPC determined by X-ray diffraction.

    PubMed Central

    Tristram-Nagle, Stephanie; Liu, Yufeng; Legleiter, Justin; Nagle, John F

    2002-01-01

    The structure of fully hydrated gel phase dimyristoylphosphatidylcholine lipid bilayers was obtained at 10 degrees C. Oriented lipid multilayers were used to obtain high signal-to-noise intensity data. The chain tilt angle and an estimate of the methylene electron density were obtained from wide angle reflections. The chain tilt angle is measured to be 32.3 +/- 0.6 degrees near full hydration, and it does not change as the sample is mildly dehydrated from a repeat spacing of D = 59.9 A to D = 56.5 A. Low angle diffraction peaks were obtained up to the tenth order for 17 samples with variable D and prepared by three different methods with different geometries. In addition to the usual Fourier reconstructions of the electron density profiles, model electron density profiles were fit to all the low angle data simultaneously while constraining the model to include the wide-angle data and the measured lipid volume. Results are obtained for area/lipid (A = 47.2 +/- 0.5 A(2)), the compressibility modulus (K(A) = 500 +/- 100 dyn/cm), various thicknesses, such as the hydrocarbon thickness (2D(C) = 30.3 +/- 0.2 A), and the head-to-head spacing (D(HH) = 40.1 +/- 0.1 A). PMID:12496100

  2. Molecular Dynamics Simulations of a DMPC Bilayer Using Nonadditive Interaction Models

    PubMed Central

    Davis, Joseph E.; Rahaman, Obaidur; Patel, Sandeep

    2009-01-01

    Abstract We present a polarizable force field based on the charge-equilibration formalism for molecular dynamics simulations of phospholipid bilayers. We discuss refinement of headgroup dihedral potential parameters to reproduce ab initio conformational energies of dimethylphosphate calculated at the MP2/cc-pVTZ level of theory. We also address the refinement of electrostatic and Lennard-Jones (van der Waals) parameters to reproduce ab initio polarizabilities and water interaction energies of dimethylphosphate and tetramethylammonium. We present results of molecular dynamics simulations of a solvated dimyristoylphosphatidylcholine bilayer using this polarizable force field as well as the nonpolarizable, fixed-charge CHARMM27 and CHARMM27r force fields for comparison. Calculated atomic and electron-density profiles, deuterium order parameters, and headgroup orientations are found to be consistent with previous simulations and with experiment. Polarizable interaction models for solvent and lipid exhibit greater water penetration into the lipid interior; this is due to the variation of water molecular dipole moment from a bulk value of 2.6 Debye to a value of 1.9 Debye in the membrane interior. The reduction in the electrostatic component of the desolvation free-energy penalty allows for greater water density. The surface dipole potential predicted by the polarizable model is 0.95 V compared to the value of 0.8 V based on nonpolarizable force-field calculations. Effects of inclusion of explicit polarization are discussed in relation to water dipole moment and varying charge distributions. Dielectric permittivity profiles for polarizable and nonpolarizable interactions exhibit subtle differences arising from the nature of the individual component parameterizations; for the polarizable force field, we obtain a bulk dielectric permittivity of 79, whereas the nonpolarizable force field plateaus at 97 (the value for pure TIP3P water). In the membrane interior, both models predict unit permittivities, with the polarizable models contributing from one to two more units due to the optical dielectric (high-frequency dipole fluctuations). This contribution is a step toward the continuing development of a CHARMM (Chemistry at Harvard Molecular Mechanics) polarizable force field for simulations of biomacromolecular systems. PMID:19167291

  3. [Small fiber neuropathy].

    PubMed

    Langlois, V; Bedat Millet, A-L; Lebesnerais, M; Miranda, S; Marguet, F; Benhamou, Y; Marcorelles, P; Lévesque, H

    2017-04-11

    Small fiber neuropathy (SFN) is still unknown. Characterised by neuropathic pain, it typically begins by burning feet, but could take many other expression. SFN affects the thinly myelinated Aδ and unmyelinated C-fibers, by an inherited or acquired mechanism, which could lead to paresthesia, thermoalgic disorder or autonomic dysfunction. Recent studies suggest the preponderant role of ion channels such as Nav1.7. Furthermore, erythromelalgia or burning mouth syndrome are now recognized as real SFN. Various aetiologies of SFN are described. It could be isolated or associated with diabetes, impaired glucose metabolism, vitamin deficiency, alcohol, auto-immune disease, sarcoidosis etc. Several mutations have recently been identified, like Nav1.7 channel leading to channelopathies. Diagnostic management is based primarily on clinical examination and demonstration of small fiber dysfunction. Laser evoked potentials, Sudoscan(®), cutaneous biopsy are the main test, but had a difficult access. Treatment is based on multidisciplinary management, combining symptomatic treatment, psychological management and treatment of an associated etiology. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  4. Small engine technology programs

    NASA Technical Reports Server (NTRS)

    Niedzwiecki, Richard W.

    1990-01-01

    Described here is the small engine technology program being sponsored at the Lewis Research Center. Small gas turbine research is aimed at general aviation, commuter aircraft, rotorcraft, and cruise missile applications. The Rotary Engine program is aimed at supplying fuel flexible, fuel efficient technology to the general aviation industry, but also has applications to other missions. The Automotive Gas Turbine (AGT) and Heavy-Duty Diesel Transport Technology (HDTT) programs are sponsored by DOE. The Compound Cycle Engine program is sponsored by the Army. All of the programs are aimed towards highly efficient engine cycles, very efficient components, and the use of high temperature structural ceramics. This research tends to be generic in nature and has broad applications. The HDTT, rotary technology, and the compound cycle programs are all examining approaches to minimum heat rejection, or 'adiabatic' systems employing advanced materials. The AGT program is also directed towards ceramics application to gas turbine hot section components. Turbomachinery advances in the gas turbine programs will benefit advanced turbochargers and turbocompounders for the intermittent combustion systems, and the fundamental understandings and analytical codes developed in the research and technology programs will be directly applicable to the system projects.

  5. Small engine technology programs

    NASA Technical Reports Server (NTRS)

    Niedzwiecki, Richard W.

    1987-01-01

    Small engine technology programs being conducted at the NASA Lewis Research Center are described. Small gas turbine research is aimed at general aviation, commutercraft, rotorcraft, and cruise missile applications. The Rotary Engine Program is aimed at supplying fuel flexible, fuel efficient technology to the general aviation industry, but also has applications to other missions. There is a strong element of synergism between the various programs in several respects. All of the programs are aimed towards highly efficient engine cycles, very efficient components, and the use of high temperature structural ceramics. This research tends to be generic in nature and has broad applications. The Heavy Duty Diesel Transport (HDTT), rotary technology, and the compound cycle programs are all examining approached to minimum heat rejection, or adiabatic systems employing advanced materials. The Automotive Gas Turbine (AGT) program is also directed towards ceramics application to gas turbine hot section components. Turbomachinery advances in the gas turbines will benefit advanced turbochargers and turbocompounders for the intermittent combustion systems, and the fundamental understandings and analytical codes developed in the research and technology programs will be directly applicable to the system projects.

  6. Increased HDL Size and Enhanced Apo A-I Catabolic Rates Are Associated With Doxorubicin-Induced Proteinuria in New Zealand White Rabbits.

    PubMed

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

    2016-03-01

    The catabolism and structure of high-density lipoproteins (HDL) may be the determining factor of their atheroprotective properties. To better understand the role of the kidney in HDL catabolism, here we characterized HDL subclasses and the catabolic rates of apo A-I in a rabbit model of proteinuria. Proteinuria was induced by intravenous administration of doxorubicin in New Zealand white rabbits (n = 10). HDL size and HDL subclass lipids were assessed by electrophoresis of the isolated lipoproteins. The catabolic rate of HDL-apo A-I was evaluated by exogenous radiolabelling with iodine-131. Doxorubicin induced significant proteinuria after 4 weeks (4.47 ± 0.55 vs. 0.30 ± 0.02 g/L of protein in urine, P < 0.001) associated with increased uremia, creatininemia, and cardiotoxicity. Large HDL2b augmented significantly during proteinuria, whereas small HDL3b and HDL3c decreased compared to basal conditions. HDL2b, HDL2a, and HDL3a subclasses were enriched with triacylglycerols in proteinuric animals as determined by the triacylglycerol-to-phospholipid ratio; the cholesterol content in HDL subclasses remained unchanged. The fractional catabolic rate (FCR) of [(131)I]-apo A-I in the proteinuric rabbits was faster (FCR = 0.036 h(-1)) compared to control rabbits group (FCR = 0.026 h(-1), P < 0.05). Apo E increased and apo A-I decreased in HDL, whereas PON-1 activity increased in proteinuric rabbits. Proteinuria was associated with an increased number of large HDL2b particles and a decreased number of small HDL3b and 3c. Proteinuria was also connected to an alteration in HDL subclass lipids, apolipoprotein content of HDL, high paraoxonase-1 activity, and a rise in the fractional catabolic rate of the [(131)I]-apo A-I.

  7. Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier Disease.

    PubMed Central

    Francis, G A; Knopp, R H; Oram, J F

    1995-01-01

    Tangier disease is a rare genetic disorder characterized by extremely low plasma levels of HDL and apo A-I, deposition of cholesteryl esters in tissues, and a high prevalence of cardiovascular disease. We examined the possibility that HDL apolipoprotein-mediated removal of cellular lipids may be defective in Tangier disease. With fibroblasts from normal subjects, purified apo A-I cleared cells of cholesteryl esters, depleted cellular free cholesterol pools available for esterification, and stimulated efflux of radiolabeled cholesterol, phosphatidylcholine, and sphingomyelin. With fibroblasts from two unrelated Tangier patients, however, apo A-I had little or no effect on any of these lipid transport processes. Intact HDL also was unable to clear cholesteryl esters from Tangier cells even though it promoted radiolabeled cholesterol efflux to levels 50-70% normal. Passive desorption of radiolabeled cholesterol or phospholipids into medium containing albumin or trypsinized HDL was normal for Tangier cells. Binding studies showed that the interaction of apo A-I with high-affinity binding sites on Tangier fibroblasts was abnormal. These results indicate that apo A-I has an impaired ability to remove cholesterol and phospholipid from Tangier fibroblasts, possibly because of a defective interaction of apo A-I with cell-surface binding sites. Failure of apo A-I to acquire cellular lipids may account for the rapid catabolism of nascent HDL particles and the low plasma HDL levels in Tangier disease. Images PMID:7615839

  8. A Model of Lipid-Free Apolipoprotein A-I Revealed by Iterative Molecular Dynamics Simulation

    PubMed Central

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

    2015-01-01

    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. PMID:25793886

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

    DOE PAGES

    Zhang, Xing; Lei, Dongsheng; Zhang, Lei; ...

    2015-03-20

    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,more » by integrating various experimental results, we proposed a new structural model for lipidfree 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.« less

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

    SciTech Connect

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

    2015-03-20

    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 lipidfree 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.

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

    PubMed

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

    2013-01-01

    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.

  12. Helical structure and stability in human apolipoprotein A-I by hydrogen exchange and mass spectrometry

    PubMed Central

    Chetty, Palaniappan Sevugan; Mayne, Leland; Lund-Katz, Sissel; Stranz, David; Englander, S. Walter; Phillips, Michael C.

    2009-01-01

    Apolipoprotein A-I (apoA-I) stabilizes anti-atherogenic high density lipoprotein particles (HDL) in the circulation and governs their biogenesis, metabolism, and functional interactions. To decipher these important structure–function relationships, it will be necessary to understand the structure, stability, and plasticity of the apoA-I molecule. Biophysical studies show that lipid-free apoA-I contains a large amount of α-helical structure but the location of this structure and its properties are not established. We used hydrogen-deuterium exchange coupled with a fragmentation-separation method and mass spectrometric analysis to study human lipid-free apoA-I in its physiologically pertinent monomeric form. The acquisition of ≈100 overlapping peptide fragments that redundantly cover the 243-residue apoA-I polypeptide made it possible to define the positions and stabilities of helical segments and to draw inferences about their interactions and dynamic properties. Residues 7–44, 54–65, 70–78, 81–115, and 147–178 form α-helices, accounting for a helical content of 48 ± 3%, in agreement with circular dichroism measurements (49%). At 3 to 5 kcal/mol in free energy of stabilization, the helices are far more stable than could be achieved in isolation, indicating mutually stabilizing helix bundle interactions. However the helical structure is dynamic, unfolding and refolding in seconds, allowing facile apoA-I reorganization during HDL particle formation and remodeling. PMID:19850866

  13. Apolipoprotein A-I structural organization in high density lipoproteins isolated from human plasma

    PubMed Central

    Huang, Rong; Gangani D. Silva, R. A.; Jerome, W. Gray; Kontush, Anatol; Chapman, M. John; Curtiss, Linda K.; Hodges, Timothy J.; Davidson, W. Sean

    2010-01-01

    High density lipoproteins (HDL) mediate cholesterol transport and protection from cardiovascular disease. Although synthetic HDLs have been studied for 30 years, the structure of human plasma-derived HDL, and its major protein apolipoprotein (apo)A-I, is unknown. We separated normal human HDL into 5 density subfractions and then further isolated those containing predominantly apoA-I (LpA-I). Using cross-linking chemistry and mass spectrometry, we found that apoA-I adopts a structural framework in these particles that closely mirrors that in synthetic HDL. We adapted established structural models for synthetic HDL to generate the first detailed models of authentic human plasma HDL in which apoA-I adopts a symmetrical cage-like structure. The models suggest that HDL particle size is modulated via a twisting motion of the resident apoA-I molecules. This understanding offers insights into how apoA-I structure modulates HDL function and its interactions with other apolipoproteins. PMID:21399642

  14. HDL-apoA-I Exchange: Rapid Detection and Association with Atherosclerosis

    PubMed Central

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

    2013-01-01

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

  15. Apolipoproteins A-I, A-II and E in cholestatic liver disease.

    PubMed

    Florén, C H; Gustafson, A

    1985-04-01

    Apolipoproteins A-I, A-II and E were determined in the plasma of nine patients (five females, four males) with cholestatic liver disease (eight patients with primary biliary cirrhosis and one patient with sclerosing cholangitis). Plasma concentrations were measured by electroimmunoassay in the fasting state, postprandially after ingestion of either 100 g fat as whipping cream or a light mixed meal with or without addition of wheat fibre. Concentrations of apolipoproteins A-I and A-II were low in patients with cholestatic liver disease and A-I levels correlated inversely with the severity of liver disease as measured by bilirubin levels (r = -0.66). No changes in plasma apolipoprotein A-I, A-II or E concentrations occurred postprandially. There was an inverse correlation between plasma concentrations of apolipoproteins A-I and E (p less than 0.05, r = -0.68). A close relation existed between the ratio of apolipoprotein E to apolipoprotein A-I and plasma bile salt concentration (r = 0.80, p less than 0.01) and serum bilirubin (r = 0.76, p less than 0.01). This implies that in cholestatic liver disease apolipoprotein E and A-I levels reflect the degree of cholestasis.

  16. Apolipoprotein A-I Modulates Atherosclerosis Through Lymphatic Vessel-Dependent Mechanisms in Mice.

    PubMed

    Milasan, Andreea; Jean, Gabriel; Dallaire, François; Tardif, Jean-Claude; Merhi, Yahye; Sorci-Thomas, Mary; Martel, Catherine

    2017-09-22

    Subcutaneously injected lipid-free apoA-I (apolipoprotein A-I) reduces accumulation of lipid and immune cells within the aortic root of hypercholesterolemic mice without increasing high-density lipoprotein-cholesterol concentrations. Lymphatic vessels are now recognized as prerequisite players in the modulation of cholesterol removal from the artery wall in experimental conditions of plaque regression, and particular attention has been brought to the role of the collecting lymphatic vessels in early atherosclerosis-related lymphatic dysfunction. In the present study, we address whether and how preservation of collecting lymphatic function contributes to the protective effect of apoA-I. Atherosclerotic Ldlr(-/-) mice treated with low-dose lipid-free apoA-I showed enhanced lymphatic transport and abrogated collecting lymphatic vessel permeability in atherosclerotic Ldlr(-/-) mice when compared with albumin-control mice. Treatment of human lymphatic endothelial cells with apoA-I increased the adhesion of human platelets on lymphatic endothelial cells, in a bridge-like manner, a mechanism that could strengthen endothelial cell-cell junctions and limit atherosclerosis-associated collecting lymphatic vessel dysfunction. Experiments performed with blood platelets isolated from apoA-I-treated Ldlr(-/-) mice revealed that apoA-I decreased ex vivo platelet aggregation. This suggests that in vivo apoA-I treatment limits platelet thrombotic potential in blood while maintaining the platelet activity needed to sustain adequate lymphatic function. Altogether, we bring forward a new pleiotropic role for apoA-I in lymphatic function and unveil new potential therapeutic targets for the prevention and treatment of atherosclerosis. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  17. Reduced Cerebrospinal Fluid Concentration of Apolipoprotein A-I in Patients with Alzheimer's Disease.

    PubMed

    Johansson, Per; Almqvist, Erik G; Bjerke, Maria; Wallin, Anders; Johansson, Jan-Ove; Andreasson, Ulf; Blennow, Kaj; Zetterberg, Henrik; Svensson, Johan

    2017-01-01

    Apolipoprotein E (ApoE) has been extensively studied in Alzheimer's disease (AD), but little is known of apolipoprotein A-I (ApoA-I) in cerebrospinal fluid (CSF). Plasma lipids as well as ApoA-I and ApoE in plasma and CSF were determined and related to Mini-Mental State Examination (MMSE) score, APOE genotype, and CSF AD biomarkers. Consecutive patients with AD (n = 29), stable mild cognitive impairment (n = 13), other dementias (n = 14), and healthy controls (n = 18) were included at a single center. AD patients had higher plasma triglycerides and lower CSF ApoA-I concentration than controls (both p < 0.05). CSF ApoE concentration was reduced in other dementias (p < 0.01). In AD as well as other dementias, the ratios between CSF and plasma concentrations of both ApoA-I and ApoE were lower than those in the controls. ApoA-I and ApoE in plasma and CSF were not influenced by APOEɛ4 allele distribution. In the total study population (n = 74), CSF ApoA-I correlated positively with MMSE score (r = 0.26, p < 0.05) and negatively with CSF P-tau (r = -0.25, p < 0.05). CSF ApoE correlated positively with CSF concentrations of T-tau and P-tau in the total study population and in AD patients. CSF ApoA-I was reduced in AD patients and associated with measures of cognitive function and AD disease status. The mechanisms underlying the decreased CSF:plasma ratios of ApoA-I and ApoE in AD and other dementias need to be explored in further studies.

  18. The Conformation of Lipid-Free Human Apolipoprotein A-I in Solution

    PubMed Central

    Pollard, Ricquita D.; Fulp, Brian; Samuel, Michael P.; Sorci-Thomas, Mary G.; Thomas, Michael J.

    2014-01-01

    Apolipoprotein AI (apoA-I) is the principal acceptor of lipids from ATP-binding cassette transporter A1, a process that yields nascent high density lipoproteins. Analysis of lipidated apoA-I conformation yields a belt or twisted belt in which two strands of apoA-I lie antiparallel to one another. In contrast, biophysical studies have suggested that a part of lipid-free apoA-I was arranged in a 4-helix bundle. To understand how lipid-free apoA-I opens from a bundle to a belt while accepting lipid it was necessary to have a more refined model for the conformation of lipid-free apoA-I. This study reports the conformation of lipid-free human apoA-I using lysine-to-lysine chemical cross-linking in conjunction with disulfide cross-linking achieved using selective cysteine mutations. After proteolysis cross-linked peptides were verified by sequencing using tandem mass spectrometry. The resulting structure is compact with roughly 4 helical regions, amino acids 44 through 186, bundled together. C- and N-terminal ends, amino acids 1-43 and 187-243, respectively, are folded such that they lie close to one another. An unusual feature of the molecule is the high degree of connectivity of lysine40 with 6 other lysines, lysines that are close, e.g., lysine59, to distant lysines, e.g., lysine239, that are at the opposite end of the primary sequence. These results are compared and contrasted with other reported conformations for lipid-free human apoA-I and an NMR study of mouse apoA-I. PMID:24308268

  19. Lysine residues of ABCA1 are required for the interaction with apoA-I.

    PubMed

    Nagao, Kohjiro; Kimura, Yasuhisa; Ueda, Kazumitsu

    2012-03-01

    ATP-binding cassette protein A1 (ABCA1) plays a pivotal role in cholesterol homeostasis by generating high-density lipoprotein (HDL). Apolipoprotein A-I (apoA-I), a lipid acceptor for ABCA1, reportedly interacts with ABCA1. However, it has also been proposed that apoA-I interacts with ABCA1-generated special domains on the plasma membrane, but apart from ABCA1, and solubilizes membrane lipids. To determine the importance of the apoA-I-ABCA1 interaction in HDL formation, the electrostatic interaction between apoA-I and ABCA1, which mediates the interaction between apoB100 in low-density lipoprotein particles (LDL) and LDL receptor, was analyzed. The apoA-I binding to ABCA1 and the cross-linking between them were inhibited by the highly charged molecules heparin and poly-L-lysine. Treating cells with membrane impermeable reagents that specifically react with primary amino groups abolished the interaction between apoA-I and ABCA1. However, these reagents did not affect the characteristic tight ATP binding to ABCA1. These results suggest that lysine residues in the extracellular domains of ABCA1 contribute to the interaction with apoA-I. The electrostatic interaction between ABCA1 and apoA-I is predicted to be the first step in HDL formation. This article is part of a Special Issue entitled Advances in high density lipoprotein formation and metabolism: a tribute to John F. Oram (1945-2010).

  20. Proteolysis of Apolipoprotein A-I by Secretory Phospholipase A2

    PubMed Central

    Cavigiolio, Giorgio; Jayaraman, Shobini

    2014-01-01

    In the acute phase of the inflammatory response, secretory phospholipase A2 (sPLA2) reaches its maximum levels in plasma, where it is mostly associated with high density lipoproteins (HDL). Overexpression of human sPLA2 in transgenic mice reduces both HDL cholesterol and apolipoprotein A-I (apoA-I) plasma levels through increased HDL catabolism by an unknown mechanism. To identify unknown PLA2-mediated activities on the molecular components of HDL, we characterized the protein and lipid products of the PLA2 reaction with HDL. Consistent with previous studies, hydrolysis of HDL phospholipids by PLA2 reduced the particle size without changing its protein composition. However, when HDL was destabilized in the presence of PLA2 by the action of cholesteryl ester transfer protein or by guanidine hydrochloride treatment, a fraction of apoA-I, but no other proteins, dissociated from the particle and was rapidly cleaved. Incubation of PLA2 with lipid-free apoA-I produced similar protein fragments in the range of 6–15 kDa, suggesting specific and direct reaction of PLA2 with apoA-I. Mass spectrometry analysis of isolated proteolytic fragments indicated at least two major cleavage sites at the C-terminal and the central domain of apoA-I. ApoA-I proteolysis by PLA2 was Ca2+-independent, implicating a different mechanism from the Ca2+-dependent PLA2-mediated phospholipid hydrolysis. Inhibition of proteolysis by benzamidine suggests that the proteolytic and lipolytic activities of PLA2 proceed through different mechanisms. Our study identifies a previously unknown proteolytic activity of PLA2 that is specific to apoA-I and may contribute to the enhanced catabolism of apoA-I in inflammation and atherosclerosis. PMID:24523407

  1. Small Syrian Volcano

    NASA Technical Reports Server (NTRS)

    2003-01-01

    MGS MOC Release No. MOC2-498, 29 September 2003

    Today, 29 September 2003, is the first day of southern summer, and the first day of northern winter on Mars. This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a small volcano in Syria Planum near 12.9oS, 102.7oW. The volcano and surrounding terrain have been thickly mantled by dust; this dust has subsequently been eroded so that it appears textured rather than smooth. The thin, light streaks that crisscross the image are the tracks left by passing dust devils. Not all dust devils on Mars make streaks, and not all streaks are darker than their surroundings--those found in Syria Planum are invariably lighter in tone. The picture covers an area 3 km (1.9 mi) across; sunlight illuminates the scene from the upper left.

  2. Small transport aircraft technology

    NASA Technical Reports Server (NTRS)

    Williams, L. J.

    1983-01-01

    Information on commuter airline trends and aircraft developments is provided to upgrade the preliminary findings of a NASA-formed small transport aircraft technology (STAT) team, established to determine whether the agency's research and development programs could help commuter aircraft manufacturers solve technical problems related to passenger acceptance and use of 19- to 50-passenger aircraft. The results and conclusions of the full set of completed STAT studies are presented. These studies were performed by five airplane manufacturers, five engine manufacturers, and two propeller manufacturers. Those portions of NASA's overall aeronautics research and development programs which are applicable to commuter aircraft design are summarized. Areas of technology that might beneficially be expanded or initiated to aid the US commuter aircraft manufacturers in the evolution of improved aircraft for the market are suggested.

  3. Modular small hydro configuration

    NASA Astrophysics Data System (ADS)

    1981-09-01

    Smaller sites (those under 750 kilowatts) which previously were not attractive to develop using equipment intended for application at larger scale sites, were the focal point in the conception of a system which utilizes standard industrial components which are generally available within short procurement times. Such components were integrated into a development scheme for sites having 20 feet to 150 feet of head. The modular small hydro configuration maximizes the use of available components and minimizes modification of existing civil works. A key aspect of the development concept is the use of a vertical turbine multistage pump, used in the reverse mode as a hydraulic turbine. The configuration allows for automated operation and control of the hydroelectric facilities with sufficient flexibility for inclusion of potential hydroelectric sites into dispersed storage and generation (DSG) utility grid systems.

  4. [Is allastrim small pox?].

    PubMed

    Tiexeira, L A

    2000-01-01

    Between 1910 and 1913, two renowned physicians in the city of Sao Paulo found themselves engaged in a scientific controversy regarding the classification of a disease then assailing the state. Antonio Carini, director of the Instituto Pasteur de Sao Paulo, believed the illness to be small pox, while Emilio Ribas, director of the Servico Sanitario, claimed it was allastrim, or milk pox. The controversy started in the Sociedade de Medicina e Cirurgia but later migrated to other forums and came to incorporate other figures as well. This presentation and discussion of the polemic is meant as a contribution to our understanding of the process by which a scientific consensus is constructed and solidified within the field of the biomedical sciences.

  5. Friction at small displacement.

    NASA Technical Reports Server (NTRS)

    Campbell, W. E.; Aronstein, J.

    1972-01-01

    Low contact resistance between metal surfaces is often observed in spite of interposed lubricant and/or oxide films. To study this effect an apparatus is used with which normal force and tangential microdisplacement are applied between a small lead rider and a gold flat with various surface film conditions. Under nonoxidized and nonlubricated conditions, and with either oxide or stearic acid lubricant film alone, friction is high and contact resistance is low. With oxide and lubricant together, friction is much lower and slide is smooth, but contact resistance remains low and Ohm's law is obeyed. The results are consistent with Greenwood's theory of contact resistance for a cluster of minute metallic contact spots within the load-supporting area. The contact resistance of such a cluster is indistinguishable, for practical purposes, from that given by complete metallic contact.

  6. Small Impact Crater

    NASA Technical Reports Server (NTRS)

    2005-01-01

    22 June 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a small impact crater with a 'butterfly' ejecta pattern. The butterfly pattern results from an oblique impact. Not all oblique impacts result in an elliptical crater, but they can result in a non-radial pattern of ejecta distribution. The two-toned nature of the ejecta -- with dark material near the crater and brighter material further away -- might indicate the nature of subsurface materials. Below the surface, there may be a layer of lighter-toned material, underlain by a layer of darker material. The impact throws these materials out in a pattern that reflects the nature of the underlying layers.

    Location near: 3.7oN, 348.2oW Image width: 3 km (1.9 mi) Illumination from: lower left Season: Northern Autumn

  7. Small dose... big poison.

    PubMed

    Braitberg, George; Oakley, Ed

    2010-11-01

    It is not possible to identify all toxic substances in a single journal article. However, there are some exposures that in small doses are potentially fatal. Many of these exposures are particularly toxic to children. Using data from poison control centres, it is possible to recognise this group of exposures. This article provides information to assist the general practitioner to identify potential toxic substance exposures in children. In this article the authors report the signs and symptoms of toxic exposures and identify the time of onset. Where clear recommendations on the period of observation and known fatal dose are available, these are provided. We do not discuss management or disposition, and advise readers to contact the Poison Information Service or a toxicologist for this advice.

  8. Small Business Innovations

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Under a Small Business Innovation Research (SBIR) contract to Kennedy Space Center, EIC Laboratories invented a Raman Spectrograph with fiber optic sampling for space applications such as sensing hazardous fuel vapors and making on-board rapid analyses of chemicals and minerals. Raman spectroscopy is a laser-based measurement technique that provides through a unique vibrational spectrum a molecular 'fingerprint,' and can function in aqueous environments. EIC combined optical fiber technology with Raman methods to develop sensors that can be operated at a distance from the spectrographic analysis instruments and the laser excitation source. EIC refined and commercialized the technology to create the Fiber Optic Raman Spectrograph and the RamanProbe. Commercial applications range from process control to monitoring hazardous materials.

  9. Three small deployed satellites

    NASA Image and Video Library

    2012-10-04

    ISS033-E-009285 (4 Oct. 2012) --- Several tiny satellites are featured in this image photographed by an Expedition 33 crew member on the International Space Station. The satellites were released outside the Kibo laboratory using a Small Satellite Orbital Deployer attached to the Japanese module’s robotic arm on Oct. 4, 2012. Japan Aerospace Exploration Agency astronaut Aki Hoshide, flight engineer, set up the satellite deployment gear inside the lab and placed it in the Kibo airlock. The Japanese robotic arm then grappled the deployment system and its satellites from the airlock for deployment. A portion of the station’s solar array panels and a blue and white part of Earth provide the backdrop for the scene.

  10. Three small deployed satellites

    NASA Image and Video Library

    2012-10-04

    ISS033-E-009286 (4 Oct. 2012) --- Several tiny satellites are featured in this image photographed by an Expedition 33 crew member on the International Space Station. The satellites were released outside the Kibo laboratory using a Small Satellite Orbital Deployer attached to the Japanese module’s robotic arm on Oct. 4, 2012. Japan Aerospace Exploration Agency astronaut Aki Hoshide, flight engineer, set up the satellite deployment gear inside the lab and placed it in the Kibo airlock. The Japanese robotic arm then grappled the deployment system and its satellites from the airlock for deployment. A portion of the station’s solar array panels and a blue and white part of Earth provide the backdrop for the scene.

  11. Small caliber guided projectile

    DOEpatents

    Jones, James F.; Kast, Brian A.; Kniskern, Marc W.; Rose, Scott E.; Rohrer, Brandon R.; Woods, James W.; Greene, Ronald W.

    2010-08-24

    A non-spinning projectile that is self-guided to a laser designated target and is configured to be fired from a small caliber smooth bore gun barrel has an optical sensor mounted in the nose of the projectile, a counterbalancing mass portion near the fore end of the projectile and a hollow tapered body mounted aft of the counterbalancing mass. Stabilizing strakes are mounted to and extend outward from the tapered body with control fins located at the aft end of the strakes. Guidance and control electronics and electromagnetic actuators for operating the control fins are located within the tapered body section. Output from the optical sensor is processed by the guidance and control electronics to produce command signals for the electromagnetic actuators. A guidance control algorithm incorporating non-proportional, "bang-bang" control is used to steer the projectile to the target.

  12. Very Small Interstellar Spacecraft

    NASA Astrophysics Data System (ADS)

    Peck, Mason A.

    2007-02-01

    This paper considers lower limits of length scale in spacecraft: interstellar vehicles consisting of little more material than found in a typical integrated-circuit chip. Some fundamental scaling principles are introduced to show how the dynamics of the very small can be used to realize interstellar travel with minimal advancements in technology. Our recent study for the NASA Institute for Advanced Concepts provides an example: the use of the Lorentz force that acts on electrically charged spacecraft traveling through planetary and stellar magnetospheres. Schaffer and Burns, among others, have used Cassini and Voyager imagery to show that this interaction is responsible for some of the resonances in the orbital dynamics of dust in Jupiter's and Saturn's rings. The Lorentz force turns out to vary in inverse proportion to the square of this characteristic length scale, making it a more effective means of propelling tiny spacecraft than solar sailing. Performance estimates, some insight into plasma interactions, and some hardware concepts are offered. The mission architectures considered here involve the use of these propellantless propulsion techniques for acceleration within our solar system and deceleration near the destination. Performance estimates, some insight into plasma interactions, and some hardware concepts are offered. The mission architectures considered here involve the use of these propellantless propulsion techniques for acceleration within our solar system and deceleration near the destination. We might envision a large number of such satellites with intermittent, bursty communications set up as a one-dimensional network to relay signals across great distances using only the power likely from such small spacecraft. Conveying imagery in this fashion may require a long time because of limited power, but the prospect of imaging another star system close-up ought to be worth the wait.

  13. Small Active Radiation Monitor

    NASA Technical Reports Server (NTRS)

    Badhwar, Gautam D.

    2004-01-01

    A device, named small active radiation monitor, allows on-orbit evaluations during periods of increased radiation, after extravehicular activities, or at predesignated times for crews on such long-duration space missions as on the International Space Station. It also permits direct evaluation of biological doses, a task now performed using a combination of measurements and potentially inaccurate simulations. Indeed the new monitor can measure a full array of radiation levels, from soft x-rays to hard galactic cosmic-ray particles. With refinement, it will benefit commercial (nuclear power-plant workers, airline pilots, medical technicians, physicians/dentists, and others) and military personnel as well as the astronauts for whom thermoluminescent dosimeters are inadequate. Civilian and military personnel have long since graduated from film badges to thermoluminescent dosimeters. Once used, most dosimeters must be returned to a central facility for processing, a step that can take days or even weeks. While this suffices for radiation workers for whom exposure levels are typically very low and of brief duration, it does not work for astronauts. Even in emergencies and using express mail, the results can often be delayed by as much as 24 hours. Electronic dosimeters, which are the size of electronic oral thermometers, and tattlers, small electronic dosimeters that sound an alarm when the dose/dose rate exceeds preset values, are also used but suffer disadvantages similar to those of thermoluminescent dosimeters. None of these devices fully answers the need of rapid monitoring during the space missions. Instead, radiation is monitored by passive detectors, which are read out after the missions. Unfortunately, these detectors measure only the absorbed dose and not the biologically relevant dose equivalent. The new monitor provides a real-time readout, a time history of radiation exposures (both absorbed dose and biologically relevant dose equivalent), and a count of the

  14. Small-crack test methods

    NASA Astrophysics Data System (ADS)

    Larsen, James M.; Allison, John E.

    This book contains chapters on fracture mechanics parameters for small fatigue cracks, monitoring small-crack growth by the replication method, measurement of small cracks by photomicroscopy (experiments and analysis), and experimental mechanics of microcracks. Other topics discussed are the real-time measurement of small-crack-opening behavior using an interferometric strain/displacement gage; direct current electrical potential measurement of the growth of small cracks; an ultrasonic method for the measurement of the size and opening behavior of small fatigue cracks; and the simulation of short crack and other low closure loading conditions, utilizing constant K(max) Delta-K-decreasing fatigue crack growth procedures.

  15. The Case for Small Universities--"Is Small Beautiful?"

    ERIC Educational Resources Information Center

    Birt, L. M.; Stewart, R. F.

    1981-01-01

    Options available to small universities in Australia in order to maximize their efficiency in lean times are discussed: staying small with better funding; staying small with standard funding; federation with another institution or institutions but with internal differentiation; merger; and closing. (MSE)

  16. Going Small: Progress & Challenges of Philadelphia's Small High Schools

    ERIC Educational Resources Information Center

    Hartmann, Tracey; Reumann-Moore, Rebecca; Evans, Shani Adia; Haxton, Clarisse; Maluk, Holly; Neild, Ruth Curran

    2009-01-01

    Between 2003 and 2007, and without significant outside funding, the School District of Philadelphia created 25 new small high schools. This study, begun by Research for Action in 2006, follows the start-up and early implementation of these small high schools in Philadelphia. The study found that parents and students are interested in small high…

  17. Using spin-label W-band EPR to study membrane fluidity profiles in samples of small volume

    PubMed Central

    Mainali, Laxman; Hyde, James S.; Subczynski, Witold K.

    2012-01-01

    Conventional and saturation-recovery (SR) EPR at W-band (94 GHz) using phosphatidylcholine spin labels (labeled at the alkyl chain [n-PC] and headgroup [T-PC]) to obtain profiles of membrane fluidity has been demonstrated. Dimyristoyl-phosphatidylcholine (DMPC) membranes with and without 50 mol% cholesterol have been studied, and the results have been compared with similar studies at X-band (9.4 GHz) (L. Mainali, J.B. Feix, J.S. Hyde, W.K. Subczynski J. Magn. Reson. 212:418-425 [2011]). Profiles of the spin-lattice relaxation rate (T1−1) obtained from SR EPR measurements for n-PCs and T-PC were used as a convenient quantitative measure of membrane fluidity. Additionally, spectral analysis using Freed’s MOMD (microscopic-order macroscopic-disorder) model (E. Meirovitch, J.H. Freed J. Phys. Chem. 88:4995-5004 [1984]) provided rotational diffusion coefficients (R⊥ and R∥) and order parameters (S0). Spectral analysis at X-band provided one rotational diffusion coefficient, R. T1−1, R⊥, and R∥ profiles reflect local membrane dynamics of the lipid alkyl chain, while the order parameter shows only the amplitude of the wobbling motion of the lipid alkyl chain. Using these dynamic parameters, namely T1−1, R⊥, and R∥, one can discriminate the different effects of cholesterol at different depths, showing that cholesterol has a rigidifying effect on alkyl chains to the depth occupied by the rigid steroid ring structure and a fluidizing effect at deeper locations. The nondynamic parameter, S0, shows that cholesterol has an ordering effect on alkyl chains at all depths. Conventional and SR EPR measurements with T-PC indicate that cholesterol has a fluidizing effect on phospholipids headgroups. EPR at W-band provides more detailed information about the depth-dependent dynamic organization of the membrane compared with information obtained at X-band. EPR at W-band has the potential to be a powerful tool for studying membrane fluidity in samples of small volume

  18. Using spin-label W-band EPR to study membrane fluidity profiles in samples of small volume

    NASA Astrophysics Data System (ADS)

    Mainali, Laxman; Hyde, James S.; Subczynski, Witold K.

    2013-01-01

    Conventional and saturation-recovery (SR) EPR at W-band (94 GHz) using phosphatidylcholine spin labels (labeled at the alkyl chain [n-PC] and headgroup [T-PC]) to obtain profiles of membrane fluidity has been demonstrated. Dimyristoylphosphatidylcholine (DMPC) membranes with and without 50 mol% cholesterol have been studied, and the results have been compared with similar studies at X-band (9.4 GHz) (L. Mainali, J.B. Feix, J.S. Hyde, W.K. Subczynski, J. Magn. Reson. 212 (2011) 418-425). Profiles of the spin-lattice relaxation rate (T1-1) obtained from SR EPR measurements for n-PCs and T-PC were used as a convenient quantitative measure of membrane fluidity. Additionally, spectral analysis using Freed's MOMD (microscopic-order macroscopic-disorder) model (E. Meirovitch, J.H. Freed J. Phys. Chem. 88 (1984) 4995-5004) provided rotational diffusion coefficients (R⊥ and R||) and order parameters (S0). Spectral analysis at X-band provided one rotational diffusion coefficient, R⊥. T1-1, R⊥, and R|| profiles reflect local membrane dynamics of the lipid alkyl chain, while the order parameter shows only the amplitude of the wobbling motion of the lipid alkyl chain. Using these dynamic parameters, namely T1-1, R⊥, and R||, one can discriminate the different effects of cholesterol at different depths, showing that cholesterol has a rigidifying effect on alkyl chains to the depth occupied by the rigid steroid ring structure and a fluidizing effect at deeper locations. The nondynamic parameter, S0, shows that cholesterol has an ordering effect on alkyl chains at all depths. Conventional and SR EPR measurements with T-PC indicate that cholesterol has a fluidizing effect on phospholipid headgroups. EPR at W-band provides more detailed information about the depth-dependent dynamic organization of the membrane compared with information obtained at X-band. EPR at W-band has the potential to be a powerful tool for studying membrane fluidity in samples of small volume, ˜30 n

  19. 11. Photographed 19131914 by L. M. Leisenring, F.A.I.A. Presented by ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. Photographed 1913-1914 by L. M. Leisenring, F.A.I.A. Presented by Mr. Leisenring 1959 - Dr. David Ross House, Annapolis Road (moved to Preservation Hill, Western Run Road, Cockeysville), Bladensburg, Prince George's County, MD

  20. 10. Photographed 19131914 by L. M. Leisenring, F.A.I.A. Presented by ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. Photographed 1913-1914 by L. M. Leisenring, F.A.I.A. Presented by Mr. Leisenring 1959 - Dr. David Ross House, Annapolis Road (moved to Preservation Hill, Western Run Road, Cockeysville), Bladensburg, Prince George's County, MD

  1. Lipid-free Apolipoprotein A-I Structure: Insights into HDL Formation and Atherosclerosis Development

    PubMed Central

    Mei, Xiaohu; Atkinson, David

    2015-01-01

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

  2. Relationship between plasma HDL subclasses distribution and apoA-I gene polymorphisms.

    PubMed

    Jia, Lianqun; Bai, Huai; Fu, Mingde; Xu, Yanhua; Yang, Yuye; Long, Shiyin

    2005-10-01

    It is generally accepted that apolipoprotein (apo) A-I is the dominant structural apolipoprotein of HDL particles and different HDL subclasses have distinct but interrelated metabolic functions. HDL is known to directly affect the atherogenic process hence changes in HDL subclasses distribution may be related to the incidence and prevalence of atherosclerosis. The ApoA-I contents (mg/l) of plasma HDL subclasses were determined by 2-dimensional gel electrophoresis coupled with immunodetection and apoA-I genotypes were assayed by PCR-RFLP in 307 Chinese subjects (169 males, 138 females). The G/G and C/C genotypes were the most frequent at -78 bp and +83 bp of apoA-I gene, respectively. There were no significant differences in the frequencies of rare A allele at -78 bp and rare T allele at +83 bp between males and females. Compared with the G/G carriers, G/A and A/A carriers had significantly higher plasma concentrations of TG, apoC-II, apoC-III, apoA-I contents of prebeta(1)-HDL, HDL(3a) and TG/HDL-C ratio. And in addition, A/A carriers had significantly lower apoA-I contents of HDL(2a) and HDL(2b). Females had increased plasma concentrations of apoA-I, HDL-C, apoA-I contents of HDL(2a) and HDL(2b) while decreased apoA-I contents of prebeta(1)-HDL, HDL(3b) and TG/HDL-C ratio as compared to males carrying the same genotype. No significant differences were demonstrated on the concentrations of plasma lipids, lipoproteins, apolipoproteins and apoA-I contents of plasma HDL subclasses between the C/C and C/T subjects. The G/A polymorphism at -78 bp of apoA-I gene was associated with changes of HDL subclasses distribution. There was a general shift towards smaller-sized HDL, which, in turn, indicated that reverse cholesterol transport (RCT) might be weakened and HDL maturation might be abnormal in the subjects with G/A mutation.

  3. Small intestine contrast injection (image)

    MedlinePlus

    ... and throat, through the stomach into the small intestine. When in place, contrast dye is introduced and ... means of demonstrating whether or not the small intestine is normal when abnormality is suspected.

  4. Disorders of the Small Intestine

    MedlinePlus

    ... Disorders of the Stomach Disorders of the Small Intestine Disorders of the Large Intestine Disorders of the Pelvic Floor Motility Testing Personal ... Disorders of the Stomach Disorders of the Small Intestine Disorders of the Large Intestine Disorders of the ...

  5. Small intestine aspirate and culture

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003731.htm Small intestine aspirate and culture To use the sharing features on this page, please enable JavaScript. Small intestine aspirate and culture is a lab test to ...

  6. Small Drinking Water System Variances

    EPA Pesticide Factsheets

    Small system variances allow a small system to install and maintain technology that can remove a contaminant to the maximum extent that is affordable and protective of public health in lieu of technology that can achieve compliance with the regulation.

  7. Identification of Apolipoprotein A-I as a Retinoic Acid-binding Protein in the Eye.

    PubMed

    Summers, Jody A; Harper, Angelica R; Feasley, Christa L; Van-Der-Wel, Hanke; Byrum, Jennifer N; Hermann, Marcela; West, Christopher M

    2016-09-02

    All-trans-retinoic acid may be an important molecular signal in the postnatal control of eye size. The goal of this study was to identify retinoic acid-binding proteins secreted by the choroid and sclera during visually guided ocular growth. Following photoaffinity labeling with all-trans-[11,12-(3)H]retinoic acid, the most abundant labeled protein detected in the conditioned medium of choroid or sclera had an apparent Mr of 27,000 Da. Following purification and mass spectrometry, the Mr 27,000 band was identified as apolipoprotein A-I. Affinity capture of the radioactive Mr 27,000 band by anti-chick apolipoprotein A-I antibodies confirmed its identity as apolipoprotein A-I. Photoaffinity labeling and fluorescence quenching experiments demonstrated that binding of retinoic acid to apolipoprotein A-I is 1) concentration-dependent, 2) selective for all-trans-retinoic acid, and 3) requires the presence of apolipoprotein A-I-associated lipids for retinoid binding. Expression of apolipoprotein A-I mRNA and protein synthesis were markedly up-regulated in choroids of chick eyes during the recovery from induced myopia, and apolipoprotein A-I mRNA was significantly increased in choroids following retinoic acid treatment. Together, these data suggest that apolipoprotein A-I may participate in a regulatory feedback mechanism with retinoic acid to control the action of retinoic acid on ocular targets during postnatal ocular growth. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Rosuvastatin 20 mg restores normal HDL-apoA-I kinetics in type 2 diabetes

    PubMed Central

    Vergès, Bruno; Florentin, Emmanuel; Baillot-Rudoni, Sabine; Petit, Jean-Michel; Brindisi, Marie Claude; Pais de Barros, Jean-Paul; Lagrost, Laurent; Gambert, Philippe; Duvillard, Laurence

    2009-01-01

    Catabolism of HDL particles is accelerated in type 2 diabetes, leading to a reduction in plasma residence time, which may be detrimental. Rosuvastatin is the most powerful statin to reduce LDL-cholesterol, but its effects on HDL metabolism in type 2 diabetes remain unknown. We performed a randomized double-blind cross-over trial of 6-week treatment period with placebo or rosuvastatin 20 mg in eight patients with type 2 diabetes. An in vivo kinetic study of HDL-apolipoprotein A-I (apoA-I) with 13C leucine was performed at the end of each treatment period. Moreover, a similar kinetic study was carried out in eight nondiabetic normolipidemic controls. Rosuvastatin significantly reduced plasma LDL-cholesterol (−51%), triglycerides (TGs) (−38%), and HDL-TG (−23%). HDL-apoA-I fractional catabolic rate (FCR) was decreased by rosuvastatin (0.25 ± 0.06 vs. 0.32 ± 0.07 pool/day, P = 0.011), leading to an increase in plasma HDL-apoA-I residence time (4.21 ± 1.02 vs. 3.30 ± 0.73 day, P = 0.011). Treatment with rosuvastatin was associated with a concomitant reduction of HDL-apoA-I production rate. The decrease in HDL-apoA-I FCR, induced by rosuvastatin, was correlated with the reduction of plasma TGs and HDL-TG. HDL apoA-I FCR and production rate values in diabetic patients on rosuvastatin were not different from those found in controls. Rosuvastatin is responsible for a 22% reduction of HDL-apoA-I FCR and restores to normal the increased HDL turnover observed in type 2 diabetes. These kinetic modifications may have beneficial effects by increasing HDL plasma residence time. PMID:19168444

  9. Apolipoprotein A-I Is a Potential Mediator of Remote Ischemic Preconditioning

    PubMed Central

    Hibert, Pierre; Prunier-Mirebeau, Delphine; Beseme, Olivia; Chwastyniak, Maggy; Tamareille, Sophie; Lamon, Delphine; Furber, Alain; Pinet, Florence; Prunier, Fabrice

    2013-01-01

    Background Remote ischemic preconditioning (RIPC) has emerged as an attractive strategy in clinical settings. Despite convincing evidence of the critical role played by circulating humoral mediators, their actual identities remain unknown. In this study, we aimed to identify RIPC-induced humoral mediators using a proteomic approach. Methods and Results Rats were exposed to 10-min limb ischemia followed by 5- (RIPC 5′) or 10-min (RIPC 10′) reperfusion prior to blood sampling. The control group only underwent blood sampling. Plasma samples were analyzed using surface-enhanced laser desorption and ionization - time of flight - mass spectrometry (SELDI-TOF-MS). Three protein peaks were selected for their significant increase in RIPC 10′. They were identified and confirmed as apolipoprotein A-I (ApoA-I). Additional rats were exposed to myocardial ischemia-reperfusion (I/R) and assigned to one of the following groups RIPC+myocardial infarction (MI) (10-min limb ischemia followed by 10-min reperfusion initiated 20 minutes prior to myocardial I/R), ApoA-I+MI (10 mg/kg ApoA-I injection 10 minutes before myocardial I/R), and MI (no further intervention). In comparison with untreated MI rats, RIPC reduced infarct size (52.2±3.7% in RIPC+MI vs. 64.9±2.6% in MI; p<0.05). Similarly, ApoA-I injection decreased infarct size (50.9±3.8%; p<0.05 vs. MI). Conclusions RIPC was associated with a plasmatic increase in ApoA-I. Furthermore, ApoA-I injection before myocardial I/R recapitulated the cardioprotection offered by RIPC in rats. This data suggests that ApoA-I may be a protective blood-borne factor involved in the RIPC mechanism. PMID:24155931

  10. Small rover exploration capabilities

    NASA Astrophysics Data System (ADS)

    Salotti, Jean-Marc; Laithier, Corentin; Machut, Benoit; Marie, Aurélien; Bruneau, Audrey; Grömer, Gernot; Foing, Bernard H.

    2015-05-01

    For a human mission to the Moon or Mars, an important question is to determine the best strategy for the choice of surface vehicles. Recent studies suggest that the first missions to Mars will be strongly constrained and that only small unpressurized vehicles will be available. We analyze the exploration capabilities and limitations of small surface vehicles from the user perspective. Following the “human centered design” paradigm, the team focused on human systems interactions and conducted the following experiments: - Another member of our team participated in the ILEWG EuroMoonMars 2013 simulation at the Mars Desert Research Station in Utah during the same period of time. Although the possible traverses were restricted, a similar study with analog space suits and quads has been carried out. - Other experiments have been conducted in an old rock quarry close to Bordeaux, France. An expert in the use of quads for all types of terrains performed a demonstration and helped us to characterize the difficulties, the risks and advantages and drawbacks of different vehicles and tools. The vehicles that will be used on the surface of Mars have not been defined yet. Nevertheless, the results of our project already show that using a light and unpressurized vehicle (in the order of 150 kg) for the mobility on the Martian surface can be a true advantage. Part of the study was dedicated to the search for appropriate tools that could be used to make

  11. An Evaluation of the Crystal Structure of C-terminal Truncated Apolipoprotein A-I in Solution Reveals Structural Dynamics Related to Lipid Binding.

    PubMed

    Melchior, John T; Walker, Ryan G; Morris, Jamie; Jones, Martin K; Segrest, Jere P; Lima, Diogo B; Carvalho, Paulo C; Gozzo, Fábio C; Castleberry, Mark; Thompson, Thomas B; Davidson, W Sean

    2016-03-04

    Apolipoprotein (apo) A-I mediates many of the anti-atherogenic functions attributed to high density lipoprotein. Unfortunately, efforts toward a high resolution structure of full-length apoA-I have not been fruitful, although there have been successes with deletion mutants. Recently, a C-terminal truncation (apoA-I(Δ185-243)) was crystallized as a dimer. The structure showed two helical bundles connected by a long, curved pair of swapped helical domains. To compare this structure to that existing under solution conditions, we applied small angle x-ray scattering and isotope-assisted chemical cross-linking to apoA-I(Δ185-243) in its dimeric and monomeric forms. For the dimer, we found evidence for the shared domains and aspects of the N-terminal bundles, but not the molecular curvature seen in the crystal. We also found that the N-terminal bundles equilibrate between open and closed states. Interestingly, this movement is one of the transitions proposed during lipid binding. The monomer was consistent with a model in which the long shared helix doubles back onto the helical bundle. Combined with the crystal structure, these data offer an important starting point to understand the molecular details of high density lipoprotein biogenesis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    PubMed

    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

    2015-11-01

    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) A-I, the principal apolipoprotein of high-density lipoproteins, to preserve the normal function of lymphatic endothelial cells treated with TNF. TNF decreased the ability of lymphatic endothelial cells to form tube-like structures. Preincubation of lymphatic endothelial cells with apoA-I attenuated the TNF-mediated inhibition of tube formation in a concentration-dependent manner. In addition, apoA-I reversed the TNF-mediated suppression of lymphatic endothelial cell migration and lymphatic outgrowth in thoracic duct rings. ApoA-I also abrogated the negative effect of TNF on lymphatic neovascularization in an ATP-binding cassette transporter A1-dependent manner. At the molecular level, this involved downregulation of TNF receptor-1 and the conservation of prospero-related homeobox gene-1 expression, a master regulator of lymphangiogenesis. ApoA-I also re-established the normal phenotype of the lymphatic network in the diaphragms of human TNF transgenic mice. ApoA-I restores the neovascularization capacity of the lymphatic system during TNF-mediated inflammation. This study provides a proof-of-concept that high-density lipoprotein-based therapeutic strategies may attenuate chronic inflammation via its action on lymphatic vasculature. © 2015 American Heart Association, Inc.

  13. Concentration and pattern changes of porcine serum apolipoprotein A-I in four different infectious diseases.

    PubMed

    Marco-Ramell, Anna; Hummel, Karin; Razzazi-Fazeli, Ebrahim; Bassols, Anna; Miller, Ingrid

    2015-02-01

    Apolipoprotein A-I (Apo A-I) is a major protein in lipid/lipoprotein metabolism and decreased serum levels have been observed in many species in response to inflammatory and infectious challenges. Little is known about the porcine homologue, therefore in this work we have characterized it through biochemical and proteomic techniques. In 2DE, porcine serum Apo A-I is found as three spots, the two more acidic ones corresponding to the mature protein, the more basic spot to the protein precursor. Despite high sequence coverage in LC-MS/MS, we did not find a sequence or PTM difference between the two mature protein species. Besides this biochemical characterization, we measured overall levels and relative species abundance of serum Apo A-I in four different viral and bacterial porcine infectious diseases. Lower overall amounts of Apo A-I were observed in Salmonella typhimurium and Escherichia coli infections. In the 2DE protein pattern, an increase of the protein precursor together with a lower level of mature protein species were detected in the porcine circovirus type 2-systemic disease and S. typhimurium infection. These results reveal that both the porcine serum Apo A-I concentration and the species pattern are influenced by the nature of the infectious disease. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Thermal Stability of Apolipoprotein A-I in High-Density Lipoproteins by Molecular Dynamics

    PubMed Central

    Jones, Martin K.; Catte, Andrea; Patterson, James C.; Gu, Feifei; Chen, Jianguo; Li, Ling; Segrest, Jere P.

    2009-01-01

    Abstract Apolipoprotein (apo) A-I is an unusually flexible protein whose lipid-associated structure is poorly understood. Thermal denaturation, which is used to measure the global helix stability of high-density lipoprotein (HDL)-associated apoA-I, provides no information about local helix stability. Here we report the use of temperature jump molecular dynamics (MD) simulations to scan the per-residue helix stability of apoA-I in phospholipid-rich HDL. When three 20 ns MD simulations were performed at 500 K on each of two particles created by MD simulations at 310 K, bilayers remained intact but expanded by 40%, and total apoA-I helicity decreased from 95% to 72%. Of significance, the conformations of the overlapping N- and C-terminal domains of apoA-I in the particles were unusually mobile, exposing hydrocarbon regions of the phospholipid to solvent; a lack of buried interhelical salt bridges in the terminal domains correlated with increased mobility. Nondenaturing gradient gels show that 40% expansion of the phospholipid surface of 100:2 particles by addition of palmitoyloleoylphosphatidylcholine exceeds the threshold of particle stability. As a unifying hypothesis, we propose that the terminal domains of apoA-I are phospholipid concentration-sensitive molecular triggers for fusion/remodeling of HDL particles. Since HDL remodeling is necessary for cholesterol transport, our model for remodeling has substantial biomedical implications. PMID:19167289

  15. Increasing apoA-I production as a target for CHD risk reduction.

    PubMed

    Dullens, Stefan P J; Plat, Jogchum; Mensink, Ronald P

    2007-10-01

    Dyslipidemia leading to coronary heart diseases (CHD) enables venues to prevent or treat CHD by other strategies than only lowering serum LDL cholesterol (LDL-C) concentrations, which is currently the most frequently targeted change. Unlike LDL-C, elevated high-density lipoprotein cholesterol (HDL-C) concentrations may protect against the development of CHD as demonstrated in numerous large-scale epidemiological studies. In this review we describe that besides elevating serum HDL-C concentrations by increasing alpha-HDL particles, approaches to elevate HDL-C concentrations by increasing pre-beta HDL particle concentrations seems more attractive. Besides infusion of apoA-I(Milano), using apoA-I mimetics, or delipidation of alpha-HDL particles, elevating de novo apoA-I production may be a suitable target to functionally increase pre-beta HDL particle concentrations. Therefore, a detailed description of the molecular pathways underlying apoA-I synthesis and secretion, completed with an overview of known effects of pharmacological and nutritional compounds on apoA-I synthesis will be presented. This knowledge may ultimately be applied in developing dietary intervention strategies to elevate apoA-I production and serum HDL-C concentrations and consequently lower CHD risk.

  16. Chromatofocusing of human high density lipoproteins and isolation of lipoproteins A and A-I.

    PubMed

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

    1983-08-29

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

  17. Human Apolipoprotein A-I-Derived Amyloid: Its Association with Atherosclerosis

    PubMed Central

    Ramella, Nahuel A.; Rimoldi, Omar J.; Prieto, Eduardo D.; Schinella, Guillermo R.; Sanchez, Susana A.; Jaureguiberry, María S.; Vela, María E.

    2011-01-01

    Amyloidoses constitute a group of diseases in which soluble proteins aggregate and deposit extracellularly in tissues. Nonhereditary apolipoprotein A-I (apoA-I) amyloid is characterized by deposits of nonvariant protein in atherosclerotic arteries. Despite being common, little is known about the pathogenesis and significance of apoA-I deposition. In this work we investigated by fluorescence and biochemical approaches the impact of a cellular microenvironment associated with chronic inflammation on the folding and pro-amyloidogenic processing of apoA-I. Results showed that mildly acidic pH promotes misfolding, aggregation, and increased binding of apoA-I to extracellular matrix elements, thus favoring protein deposition as amyloid like-complexes. In addition, activated neutrophils and oxidative/proteolytic cleavage of the protein give rise to pro amyloidogenic products. We conclude that, even though apoA-I is not inherently amyloidogenic, it may produce non hereditary amyloidosis as a consequence of the pro-inflammatory microenvironment associated to atherogenesis. PMID:21811627

  18. All Shops Great and Small.

    ERIC Educational Resources Information Center

    Carman, Bernard R.

    1994-01-01

    The functions of public relations offices are described for four small colleges and one small private school: Spelman College (Georgia); North Harris County College (Texas); Scripps College (California); Lafayette College (Pennsylvania); and Maumee Valley Country Day School (Ohio). Focus is on creative and effective use of a small staff and…

  19. Small Business Management. Teacher Edition.

    ERIC Educational Resources Information Center

    Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

    This instructor's guide, which is designed to assist teachers in providing instruction and technical support to small business owners and managers, contains 17 competency-based units of instruction on the following areas that both small business instructors and small business owners have deemed critical to the success of any business:…

  20. All Shops Great and Small.

    ERIC Educational Resources Information Center

    Carman, Bernard R.

    1994-01-01

    The functions of public relations offices are described for four small colleges and one small private school: Spelman College (Georgia); North Harris County College (Texas); Scripps College (California); Lafayette College (Pennsylvania); and Maumee Valley Country Day School (Ohio). Focus is on creative and effective use of a small staff and…

  1. Small Business Management. Teacher Edition.

    ERIC Educational Resources Information Center

    Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

    This instructor's guide, which is designed to assist teachers in providing instruction and technical support to small business owners and managers, contains 17 competency-based units of instruction on the following areas that both small business instructors and small business owners have deemed critical to the success of any business:…

  2. Introduction to Small Group Discussion.

    ERIC Educational Resources Information Center

    Millar, Dan Pyle

    To bring educational research into focus with tested classroom practice, this booklet provides an introduction to small group discussion. The theory and research section discusses the importance of small group discussion, characteristics of small group discussions, group attraction based on Maslow's hierarchy of basic human needs, group decision…

  3. Small fibre neuropathy.

    PubMed

    Lauria, Giuseppe; Merkies, Ingemar S J; Faber, Catharina G

    2012-10-01

    This review summarizes the most recent advances in classification, diagnostic assessment, and treatment of small fibre neuropathy (SFN). Clinically based diagnostic criteria for SFN have been proposed and reliably supported by the recent availability of age-adjusted and sex-adjusted normative values for intraepidermal nerve fibre density. Apart from skin biopsy, corneal confocal microscopy and nociceptive evoked potentials have been implemented to investigate SFN of different causes, and correlated with skin biopsy findings, especially in diabetic patients. The association between SFN and several metabolic and immune-mediated systemic diseases, and drugs toxic to this subset of peripheral nerve fibres has been reported. An exciting advance has been the identification of gain-of-function mutations in the SCN9A gene encoding for Nav1.7 sodium channel in patients with SFN, leading to the definition of a new genetic channelopathy. SFN represents a distinct condition encountered in patients with different acquired and genetic disorders. The recent improved definition of clinical and skin biopsy criteria allows clinicians to reliably meet the diagnosis, identify the underlying cause, and prescribe appropriate treatments. This meaningful approach permits the correct management of patients in clinical practice and the design of symptomatic and disease-modifying clinical trials.

  4. Small Gullied Crater

    NASA Technical Reports Server (NTRS)

    2004-01-01

    18 November 2004 Middle- and polar-latitude martian gullies remain as much a mystery today as they were when first announced in June 2000. Some have argued that they form by running water, others argue they required carbon dioxide in liquid or gas form, still others have proposed that these features form 'dry' by simple landsliding processes (although landslides elsewhere on Mars do not form features that look like the martian gullies). They occur almost exclusively at latitudes higher than 30o in both hemispheres, although they are more common in the southern hemisphere. This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a very small gully example in a crater that is only about 1 km across -- roughly the size of the famous Meteor Crater in northern Arizona. The debris transported through the gullies was deposited on top of light-toned, windblown ripples on the floor of the crater, indicating that the ripples are older. This crater is located near 37.9oS, 169.3oW. The 150 meter scale bar is about 490 feet long. Sunlight illuminates the scene from the upper left.

  5. Small scale sanitation technologies.

    PubMed

    Green, W; Ho, G

    2005-01-01

    Small scale systems can improve the sustainability of sanitation systems as they more easily close the water and nutrient loops. They also provide alternate solutions to centrally managed large scale infrastructures. Appropriate sanitation provision can improve the lives of people with inadequate sanitation through health benefits, reuse products as well as reduce ecological impacts. In the literature there seems to be no compilation of a wide range of available onsite sanitation systems around the world that encompasses black and greywater treatment plus stand-alone dry and urine separation toilet systems. Seventy technologies have been identified and classified according to the different waste source streams. Sub-classification based on major treatment methods included aerobic digestion, composting and vermicomposting, anaerobic digestion, sand/soil/peat filtration and constructed wetlands. Potential users or suppliers of sanitation systems can choose from wide range of technologies available and examine the different treatment principles used in the technologies. Sanitation systems need to be selected according to the local social, economic and environmental conditions and should aim to be sustainable.

  6. 48 CFR 970.1907 - Subcontracting with Small Business, Small Disadvantaged Business and Woman-Owned Small Business...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Business, Small Disadvantaged Business and Woman-Owned Small Business Concerns. 970.1907 Section 970.1907... MANAGEMENT AND OPERATING CONTRACTS Small, Small Disadvantaged and Women-Owned Small Business Concerns 970.1907 Subcontracting with Small Business, Small Disadvantaged Business and Woman-Owned Small...

  7. Small Thermophotovoltaic Prototype Systems

    NASA Astrophysics Data System (ADS)

    Durisch, Wilhelm; Bitnar, Bernd; von Roth, Fritz; Palfinger, Günther

    2003-01-01

    In an earlier paper [1], we reported on a small grid-connected thermophotovoltaic (TPV) system consisting of an ytterbia mantle emitter and silicon solar cells with 16 % efficiency (under solar irradiance at Standard Test Conditions, STC). The emitter was heated up using a butane burner with a rated thermal power of 1.35 kW (referring to the lower heating value). This system produced an electrical output of 15 W, which corresponds to a thermal to electric (direct current) conversion efficiency of 1.1 %. In the interim, further progress has been made, and significantly higher efficiencies have been achieved. The most important development steps are: 1) The infrared radiation-absorbing water filter between emitter and silicon cells (to protect the cells against overheating and against contact with flue gasses) has been replaced by a suitable glass tube. By doing this, it has been possible to prevent losses of convertible radiation in water. 2) Cell cooling has been significantly improved, in order to reduce cell temperature, and therefore increase conversion efficiency. 3) The shape of the emitter has been changed from spherical to a quasi-cylindrical geometry, in order to obtain a more homogeneous irradiation of the cells. 4) The metallic burner tube, on which the ytterbia emitter was fixed in the initial prototypes, has been replaced by a heat-resistant metallic rod, carrying ceramic discs as emitter holders. This has prevented the oxidation and clogging of the perforated burner tube. 5) Larger reflectors have been used to reduce losses in useful infrared radiation. 6) Smaller cells have been used, to reduce electrical series resistance losses. Applying all these improvements to the basic 1.35 kW prototype, we attained a system efficiency of 1.5 %. By using preheated air for combustion (at approximately 370 °C), 1.8 % was achieved. In a subsequent step, a photocell generator was constructed, consisting of high-efficiency silicon cells (21% STC efficiency). In this

  8. Small quenches and thermalization

    NASA Astrophysics Data System (ADS)

    Kennes, D. M.; Pommerening, J. C.; Diekmann, J.; Karrasch, C.; Meden, V.

    2017-01-01

    We study the expectation values of observables and correlation functions at long times after a global quantum quench. Our focus is on metallic ("gapless") fermionic many-body models and small quenches. The system is prepared in an eigenstate of an initial Hamiltonian, and the time evolution is performed with a final Hamiltonian which differs from the initial one in the value of one global parameter. We first derive general relations between time-averaged expectation values of observables as well as correlation functions and those obtained in an eigenstate of the final Hamiltonian. Our results are valid to linear and quadratic order in the quench parameter g and generalize prior insights in several essential ways. This allows us to develop a phenomenology for the thermalization of local quantities up to a given order in g . Our phenomenology is put to a test in several case studies of one-dimensional models representative of four distinct classes of Hamiltonians: quadratic ones, effectively quadratic ones, those characterized by an extensive set of (quasi-) local integrals of motion, and those for which no such set is known (and believed to be nonexistent). We show that for each of these models, all observables and correlation functions thermalize to linear order in g . The more local a given quantity, the longer the linear behavior prevails when increasing g . Typical local correlation functions and observables for which the term O (g ) vanishes thermalize even to order g2. Our results show that lowest-order thermalization of local observables is an ubiquitous phenomenon even in models with extensive sets of integrals of motion.

  9. Small angle neutron scattering

    NASA Astrophysics Data System (ADS)

    Cousin, Fabrice

    2015-10-01

    Small Angle Neutron Scattering (SANS) is a technique that enables to probe the 3-D structure of materials on a typical size range lying from ˜ 1 nm up to ˜ a few 100 nm, the obtained information being statistically averaged on a sample whose volume is ˜ 1 cm3. This very rich technique enables to make a full structural characterization of a given object of nanometric dimensions (radius of gyration, shape, volume or mass, fractal dimension, specific area…) through the determination of the form factor as well as the determination of the way objects are organized within in a continuous media, and therefore to describe interactions between them, through the determination of the structure factor. The specific properties of neutrons (possibility of tuning the scattering intensity by using the isotopic substitution, sensitivity to magnetism, negligible absorption, low energy of the incident neutrons) make it particularly interesting in the fields of soft matter, biophysics, magnetic materials and metallurgy. In particular, the contrast variation methods allow to extract some informations that cannot be obtained by any other experimental techniques. This course is divided in two parts. The first one is devoted to the description of the principle of SANS: basics (formalism, coherent scattering/incoherent scattering, notion of elementary scatterer), form factor analysis (I(q→0), Guinier regime, intermediate regime, Porod regime, polydisperse system), structure factor analysis (2nd Virial coefficient, integral equations, characterization of aggregates), and contrast variation methods (how to create contrast in an homogeneous system, matching in ternary systems, extrapolation to zero concentration, Zero Averaged Contrast). It is illustrated by some representative examples. The second one describes the experimental aspects of SANS to guide user in its future experiments: description of SANS spectrometer, resolution of the spectrometer, optimization of spectrometer

  10. Small Mercury Relativity Orbiter

    NASA Technical Reports Server (NTRS)

    Bender, Peter L.; Vincent, Mark A.

    1989-01-01

    The accuracy of solar system tests of gravitational theory could be very much improved by range and Doppler measurements to a Small Mercury Relativity Orbiter. A nearly circular orbit at roughly 2400 km altitude is assumed in order to minimize problems with orbit determination and thermal radiation from the surface. The spacecraft is spin-stabilized and has a 30 cm diameter de-spun antenna. With K-band and X-band ranging systems using a 50 MHz offset sidetone at K-band, a range accuracy of 3 cm appears to be realistically achievable. The estimated spacecraft mass is 50 kg. A consider-covariance analysis was performed to determine how well the Earth-Mercury distance as a function of time could be determined with such a Relativity Orbiter. The minimum data set is assumed to be 40 independent 8-hour arcs of tracking data at selected times during a two year period. The gravity field of Mercury up through degree and order 10 is solved for, along with the initial conditions for each arc and the Earth-Mercury distance at the center of each arc. The considered parameters include the gravity field parameters of degree 11 and 12 plus the tracking station coordinates, the tropospheric delay, and two parameters in a crude radiation pressure model. The conclusion is that the Earth-Mercury distance can be determined to 6 cm accuracy or better. From a modified worst-case analysis, this would lead to roughly 2 orders of magnitude improvement in the knowledge of the precession of perihelion, the relativistic time delay, and the possible change in the gravitational constant with time.

  11. Small Mercury Relativity Orbiter

    NASA Astrophysics Data System (ADS)

    Bender, Peter L.; Vincent, Mark A.

    1989-08-01

    The accuracy of solar system tests of gravitational theory could be very much improved by range and Doppler measurements to a Small Mercury Relativity Orbiter. A nearly circular orbit at roughly 2400 km altitude is assumed in order to minimize problems with orbit determination and thermal radiation from the surface. The spacecraft is spin-stabilized and has a 30 cm diameter de-spun antenna. With K-band and X-band ranging systems using a 50 MHz offset sidetone at K-band, a range accuracy of 3 cm appears to be realistically achievable. The estimated spacecraft mass is 50 kg. A consider-covariance analysis was performed to determine how well the Earth-Mercury distance as a function of time could be determined with such a Relativity Orbiter. The minimum data set is assumed to be 40 independent 8-hour arcs of tracking data at selected times during a two year period. The gravity field of Mercury up through degree and order 10 is solved for, along with the initial conditions for each arc and the Earth-Mercury distance at the center of each arc. The considered parameters include the gravity field parameters of degree 11 and 12 plus the tracking station coordinates, the tropospheric delay, and two parameters in a crude radiation pressure model. The conclusion is that the Earth-Mercury distance can be determined to 6 cm accuracy or better. From a modified worst-case analysis, this would lead to roughly 2 orders of magnitude improvement in the knowledge of the precession of perihelion, the relativistic time delay, and the possible change in the gravitational constant with time.

  12. Small 'l' leadership.

    PubMed

    Parsons, Jenni

    2009-05-01

    Recently I attended the RACGP Leadership Masterclass in Sydney. When I enrolled, I thought, 'Yes... sounds interesting...good speakers... I need to learn something about leadership...'As the time drew closer I started to get a bit anxious about the whole thing. I realised that the title, 'Masterclass', probably implied that the attendees were expected to already know something about leadership and its theories, if not have considerable expertise and experience in leadership. I also wondered how the workshop sessions were going to go and I started to feel a bit sorry for the facilitators. Imagine trying to facilitate a group of 10 aspiring leaders... a bit like trying to herd cats. A few days later I received a call from the organisers,saying they were a bit short of facilitators and could I help out if necessary. Great... better do a crash course in cat herding! Then there was the first 'predisposing activity'. Step 1: think of leaders you admire. Easy enough. Leaders of social justice and social change on a world stage, people who have shown great courage of their convictions and great orators popped into my head... Ghandi, Martin Luther King, Mandela, JFK. Step 2:describe the ways in which you are like these leaders. Whoa!Never going to measure up here. I wondered if there was going to be sessions on 'leadership for introverts', or 'leadership of small things', or 'leaders without grand vision or fabulous oratory skills', or perhaps 'leadership for people who are deeply suspicious of the corrupting influence of power'.

  13. Nematode endogenous small RNA pathways

    PubMed Central

    Hoogstrate, Suzanne W; Volkers, Rita JM; Sterken, Mark G; Kammenga, Jan E; Snoek, L Basten

    2014-01-01

    The discovery of small RNA silencing pathways has greatly extended our knowledge of gene regulation. Small RNAs have been presumed to play a role in every field of biology because they affect many biological processes via regulation of gene expression and chromatin remodeling. Most well-known examples of affected processes are development, fertility, and maintenance of genome stability. Here we review the role of the three main endogenous small RNA silencing pathways in Caenorhabditis elegans: microRNAs, endogenous small interfering RNAs, and PIWI-interacting RNAs. After providing an entry-level overview on how these pathways function, we discuss research on other nematode species providing insight into the evolution of these small RNA pathways. In understanding the differences between the endogenous small RNA pathways and their evolution, a more comprehensive picture is formed of the functions and effects of small RNAs. PMID:25340013

  14. Apolipoprotein A-I inhibits experimental colitis and colitis-propelled carcinogenesis.

    PubMed

    Gkouskou, K K; Ioannou, M; Pavlopoulos, G A; Georgila, K; Siganou, A; Nikolaidis, G; Kanellis, D C; Moore, S; Papadakis, K A; Kardassis, D; Iliopoulos, I; McDyer, F A; Drakos, E; Eliopoulos, A G

    2016-05-12

    In both humans with long-standing ulcerative colitis and mouse models of colitis-associated carcinogenesis (CAC), tumors develop predominantly in the distal part of the large intestine but the biological basis of this intriguing pathology remains unknown. Herein we report intrinsic differences in gene expression between proximal and distal colon in the mouse, which are augmented during dextran sodium sulfate (DSS)/azoxymethane (AOM)-induced CAC. Functional enrichment of differentially expressed genes identified discrete biological pathways operating in proximal vs distal intestine and revealed a cluster of genes involved in lipid metabolism to be associated with the disease-resistant proximal colon. Guided by this finding, we have further interrogated the expression and function of one of these genes, apolipoprotein A-I (ApoA-I), a major component of high-density lipoprotein. We show that ApoA-I is expressed at higher levels in the proximal compared with the distal part of the colon and its ablation in mice results in exaggerated DSS-induced colitis and disruption of epithelial architecture in larger areas of the large intestine. Conversely, treatment with an ApoA-I mimetic peptide ameliorated the phenotypic, histopathological and inflammatory manifestations of the disease. Genetic interference with ApoA-I levels in vivo impacted on the number, size and distribution of AOM/DSS-induced colon tumors. Mechanistically, ApoA-I was found to modulate signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB activation in response to the bacterial product lipopolysaccharide with concomitant impairment in the production of the pathogenic cytokine interleukin-6. Collectively, these data demonstrate a novel protective role for ApoA-I in colitis and CAC and unravel an unprecedented link between lipid metabolic processes and intestinal pathologies.

  15. Increased methionine sulfoxide content of apoA-I in type 1 diabetes.

    PubMed

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

    2008-04-01

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

  16. Renal apolipoprotein A-I amyloidosis: a rare and usually ignored cause of hereditary tubulointerstitial nephritis.

    PubMed

    Gregorini, Gina; Izzi, Claudia; Obici, Laura; Tardanico, Regina; Röcken, Christoph; Viola, Battista Fabio; Capistrano, Mariano; Donadei, Simona; Biasi, Luciano; Scalvini, Tiziano; Merlini, Giampaolo; Scolari, Francesco

    2005-12-01

    Apolipoprotein A-I amyloidosis is a rare, late-onset, autosomal dominant condition characterized by systemic deposition of amyloid in tissues, the major clinical problems being related to renal, hepatic, and cardiac involvement. Described is the clinical and histologic picture of renal involvement as a result of apolipoprotein A-I amyloidosis in five families of Italian ancestry. In all of the affected family members, the disease was caused by the Leu75Pro heterozygous mutation in exon 4 of apolipoprotein A-I gene, as demonstrated by direct sequencing and RFLP analysis. Immunohistochemistry confirmed that amyloid deposits were specifically stained with an anti-apolipoprotein A-I antibody. The clinical phenotype was mainly characterized by a variable combination of kidney and liver disturbance. The occurrence of renal involvement seemed to be almost universal, although its severity varied greatly ranging from subclinical organ damage to overt, slowly progressive renal dysfunction. The renal presentation was consistent with a tubulointerstitial disease, as suggested by the findings of defective urine-concentrating capacity, moderate polyuria, negative urinalysis, and mild tubular proteinuria. Histology confirmed tubulointerstitial nephritis. Surprising, amyloid was restricted to nonglomerular regions and limited to the renal medulla. This location of apolipoprotein A-I amyloid differs sharply from other systemic amyloidoses that are mainly characterized by glomerular and vascular deposits. The tubulointerstitial nephritis as a result of hereditary apolipoprotein A-I amyloidosis is a rare disease and a challenging diagnosis to recognize. Patients who present with familial tubulointerstitial nephritis associated with liver disease require a high index of suspicion for apolipoprotein A-I amyloidosis.

  17. Apolipoprotein A-I Helsinki promotes intracellular acyl-CoA cholesterol acyltransferase (ACAT) protein accumulation.

    PubMed

    Toledo, Juan D; Garda, Horacio A; Cabaleiro, Laura V; Cuellar, Angela; Pellon-Maison, Magali; Gonzalez-Baro, Maria R; Gonzalez, Marina C

    2013-05-01

    Reverse cholesterol transport is a process of high antiatherogenic relevance in which apolipoprotein AI (apoA-I) plays an important role. The interaction of apoA-I with peripheral cells produces through mechanisms that are still poorly understood the mobilization of intracellular cholesterol depots toward plasma membrane. In macrophages, these mechanisms seem to be related to the modulation of the activity of acyl-CoA cholesterol acyltransferase (ACAT), the enzyme responsible for the intracellular cholesterol ester biosynthesis that is stored in lipid droplets. The activation of ACAT and the accumulation of lipid droplets play a key role in the transformation of macrophages into foam cells, leading to the formation of atheroma or atherosclerotic plaque. ApoA-I Helsinki (or ∆K107) is a natural apoA-I variant with a lysine deletion in the central protein region, carriers of which have increased atherosclerosis risk. We herein show that treatment of cultured RAW macrophages or CHOK1 cells with ∆K107, but not with wild-type apoA-I or a variant containing a similar deletion at the C-terminal region (∆K226), lead to a marked increase (more than 10 times) in the intracellular ACAT1 protein level as detected by western blot analysis. However, we could only detect a slight increase in cholesteryl ester produced by ∆K107 mainly when Chol loading was supplied by low-density lipoprotein (LDL). Although a similar choline-phospholipid efflux is evoked by these apoA-I variants, the change in phosphatidylcholine/sphyngomyelin distribution produced by wild-type apoA-I is not observed with either ∆K107 or ∆K226.

  18. Discovery of RNA Binding Small Molecules Using Small Molecule Microarrays.

    PubMed

    Connelly, Colleen M; Abulwerdi, Fardokht A; Schneekloth, John S

    2017-01-01

    New methods to identify RNA-binding small molecules open yet unexplored opportunities for the pharmacological modulation of RNA-driven biology and disease states. One such approach is the use of small molecule microarrays (SMMs). Typically, SMMs are generated by spatially arraying and covalently linking a library of small molecules to a glass surface. Next, incubation of the arrays with a fluorescently labeled RNA reveals binding interactions that are detected upon slide imaging. The relative ease with which SMMs are manufactured enables the screening of multiple oligonucleotides in parallel against tens of thousands of small molecules, providing information about both binding and selectivity of identified RNA-small molecule interactions. This approach is useful for screening a broad variety of structurally and functionally diverse RNAs. Here, we present a general method for the preparation and use of SMMs to rapidly identify small molecules that selectively bind to an RNA of interest.

  19. Small Bowel Hamartoma: A Huge Diverticulum of Small Bowel

    PubMed Central

    Eltweri, Amar M.; Salama, Yahya; Gorgees, Neshtman; Naidu, Leena; Bowrey, David J.

    2013-01-01

    A-20-year old male, with no significant medical history, presented with clinical features mimicking a perforated acute appendicitis. Because of features of peritonitis, a laparotomy was performed which showed a segment of small bowel with multiple large diverticula and mesenteric cysts. A segmental small bowel resection was performed. The patient made an uneventful recovery from surgery. Histology revealed features of a small bowel hamartoma. PMID:24454405

  20. Jupiter small satellite montage

    NASA Technical Reports Server (NTRS)

    2000-01-01

    A montage of images of the small inner moons of Jupiter from the camera onboard NASA's Galileo spacecraft shows the best views obtained of these moons during Galileo's 11th orbit around the giant planet in November 1997. At that point, Galileo was completing its first two years in Jupiter orbit--known as the Galileo 'prime mission'--and was about to embark on a successful two-year extension, called the Galileo Europa Mission.

    The top two images show the moon Thebe. Thebe rotates by approximately 50 degrees between the time these two images were taken, so that the same prominent impact crater is seen in both views; this crater, which has been given the provisional name Zethus, is near the point on Thebe that faces permanently away from Jupiter.

    The next two images show the moon Amalthea; they were taken with the Sun directly behind the observer, an alignment that emphasizes patterns of intrinsically bright or dark surface material. The third image from the top is a view of Amalthea's leading side, the side of the moon that 'leads' as Amalthea moves in its orbit around Jupiter. This image looks 'noisy' because it was obtained serendipitously during an observation of the Jovian satellite Io (Amalthea and Io shared the same camera frame but the image was exposed for bright Io rather than for the much darker Amalthea). The fourth image from the top emphasizes prominent 'spots' of relatively bright material that are located near the point on Amalthea that faces permanently away from Jupiter. The bottom image is a view of the tiny moon Metis.

    In all the images, north is approximately up, and the moons are shown in their correct relative sizes. The images are, from top to bottom: Thebe taken on November 7, 1997 at a range of 504,000 kilometers (about 313,000 miles); Thebe on November 7, 1997 at a range of 548,000 kilometers (about 340,000 miles); Amalthea on November 6, 1997 at a range of about 650,000 kilometers (about 404,000 miles); Amalthea on November

  1. Small Business Innovation Research and Small Business Technology Transfer Programs

    NASA Technical Reports Server (NTRS)

    Garrison, Lynn; Jasper, Gwen

    2015-01-01

    The Small Business Innovation Research (SBIR)/Small Business Technology Transfer (STTR) programs fund the research, development, and demonstration of innovative technologies that fulfill NASA's needs as described in the annual Solicitations and have significant potential for successful commercialization. The only eligible participants are small business concern (SBC) with 500 or fewer employees or a nonprofit research institute such as a university or a research laboratory with ties to an SBC. These programs are potential sources of seed funding for the development of small business innovations.

  2. HDL-apolipoprotein A-I exchange is independently associated with cholesterol efflux capacity

    PubMed Central

    Borja, Mark S.; Ng, Kit F.; Irwin, Angela; Hong, Jaekyoung; Wu, Xing; Isquith, Daniel; Zhao, Xue-Qiao; Prazen, Bryan; Gildengorin, Virginia; Oda, Michael N.; Vaisar, Tomáš

    2015-01-01

    HDL is the primary mediator of cholesterol mobilization from the periphery to the liver via reverse cholesterol transport (RCT). A critical first step in this process is the uptake of cholesterol from lipid-loaded macrophages by HDL, a function of HDL inversely associated with prevalent and incident cardiovascular disease. We hypothesized that the dynamic ability of HDL to undergo remodeling and exchange of apoA-I is an important and potentially rate-limiting aspect of RCT. In this study, we investigated the relationship between HDL-apoA-I exchange (HAE) and serum HDL cholesterol (HDL-C) efflux capacity. We compared HAE to the total and ABCA1-specific cholesterol efflux capacity of 77 subjects. We found that HAE was highly correlated with both total (r = 0.69, P < 0.0001) and ABCA1-specific (r = 0.47, P < 0.0001) efflux, and this relationship remained significant after adjustment for HDL-C or apoA-I. Multivariate models of sterol efflux capacity indicated that HAE accounted for approximately 25% of the model variance for both total and ABCA1-specific efflux. We conclude that the ability of HDL to exchange apoA-I and remodel, as measured by HAE, is a significant contributor to serum HDL efflux capacity, independent of HDL-C and apoA-I, indicating that HDL dynamics are an important factor in cholesterol efflux capacity and likely RCT. PMID:26254308

  3. In situ AFM imaging of apolipoprotein A-I directly derived from plasma HDL.

    PubMed

    Gan, Chaoye; Wang, Zhexuan; Chen, Yong

    2017-04-01

    The major apolipoproteins of plasma lipoproteins play vital roles in the structural integrity and physiological functions of lipoproteins. More than ten structural models of apolipoprotein A-I (apoA-I), the major apolipoprotein of high-density lipoprotein (HDL), have been developed successively. In these models, apoA-I was supposed to organize in a ring-shaped form. To date, however, there is no direct evidence under physiological condition. Here, atomic force microscopy (AFM) was used to in situ visualize the organization of apoA-I, which was exposed via depletion of the lipid component of plasma HDL pre-immobilized on functionalized mica sheets. For the first time, the ring-shaped coarse structure and three detailed structures (crescent-shaped, gapped "O"-shaped, and parentheses-shaped structures, respectively) of apoA-I in plasma HDL, which have the ability of binding scavenger receptors, were directly observed and quantitatively measured by AFM. The three detailed structures probably represent the different extents to which the lipid component of HDL was depleted. Data on lipid depletion of HDL may provide clues to understand lipid insertion of HDL. These data provide important information for the understanding of the structure/maturation of plasma HDL. Moreover, they suggest a powerful method for directly visualizing the major apolipoproteins of plasma lipoproteins or the protein component of lipoprotein-like lipid-protein complexes. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. FAMP, a novel apoA-I mimetic peptide, suppresses aortic plaque formation through promotion of biological HDL function in ApoE-deficient mice.

    PubMed

    Uehara, Yoshinari; Ando, Setsuko; Yahiro, Eiji; Oniki, Kosuke; Ayaori, Makoto; Abe, Satomi; Kawachi, Emi; Zhang, Bo; Shioi, Seijiro; Tanigawa, Hiroyuki; Imaizumi, Satoshi; Miura, Shin-Ichiro; Saku, Keijiro

    2013-05-24

    Apolipoprotein (apo) A-I is a major high-density lipoprotein (HDL) protein that causes cholesterol efflux from peripheral cells through the ATP-binding cassette transporter A1 (ABCA1), thus generating HDL and reversing the macrophage foam cell phenotype. Pre-β1 HDL is the smallest subfraction of HDL, which is believed to represent newly formed HDL, and it is the most active acceptor of free cholesterol. Furthermore it has a possible protective function against cardiovascular disease (CVD). We developed a novel apoA-I mimetic peptide without phospholipids (Fukuoka University ApoA-I Mimetic Peptide, FAMP). FAMP type 5 (FAMP5) had a high capacity for cholesterol efflux from A172 cells and mouse and human macrophages in vitro, and the efflux was mainly dependent on ABCA1 transporter. Incubation of FAMP5 with human HDL or whole plasma generated small HDL particles, and charged apoA-I-rich particles migrated as pre-β HDL on agarose gel electrophoresis. Sixteen weeks of treatment with FAMP5 significantly suppressed aortic plaque formation (scrambled FAMP, 31.3 ± 8.9% versus high-dose FAMP5, 16.2 ± 5.0%; P<0.01) and plasma C-reactive protein and monocyte chemoattractant protein-1 in apoE-deficient mice fed a high-fat diet. In addition, it significantly enhanced HDL-mediated cholesterol efflux capacity from the mice. A newly developed apoA-I mimetic peptide, FAMP, has an antiatherosclerotic effect through the enhancement of the biological function of HDL. FAMP may have significant atheroprotective potential and prove to be a new therapeutic tool for CVD.

  5. Adult small bowel obstruction.

    PubMed

    Taylor, Mark R; Lalani, Nadim

    2013-06-01

    Small bowel obstruction (SBO) is a clinical condition that is often initially diagnosed and managed in the emergency department (ED). The high rates of potential complications that are associated with an SBO make it essential for the emergency physician (EP) to make a timely and accurate diagnosis. The primary objective was to perform a systematic review and meta-analysis of the history, physical examination, and imaging modalities associated with the diagnosis of SBO. The secondary objectives were to identify the prevalence of SBO in prospective ED-based studies of adult abdominal pain and to apply Pauker and Kassirer's threshold approach to clinical decision-making to the diagnosis and management of SBO. MEDLINE, EMBASE, major emergency medicine (EM) textbooks, and the bibliographies of selected articles were scanned for studies that assessed one or more components of the history, physical examination, or diagnostic imaging modalities used for the diagnosis of SBO. The selected articles underwent a quality assessment by two of the authors using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Data used to compile sensitivities and specificities were obtained from these studies and a meta-analysis was performed on those that examined the same historical component, physical examination technique, or diagnostic test. Separate information on the prevalence and management of SBO was used in conjunction with the meta-analysis findings of computed tomography (CT) to determine the test and treatment threshold. The prevalence of SBO in the ED was determined to be approximately 2% of all patients who present with abdominal pain. Having a previous history of abdominal surgery, constipation, abnormal bowel sounds, and/or abdominal distention on examination were the best history and physical examination predictors of SBO. X-ray was determined to be the least useful imaging modality for the diagnosis of SBO, with a pooled positive likelihood ratio (+LR

  6. Inducing apolipoprotein A-I synthesis to reduce cardiovascular risk: from ASSERT to SUSTAIN and beyond.

    PubMed

    Di Bartolo, Belinda A; Scherer, Daniel J; Nicholls, Stephen J

    2016-12-01

    Increasing attention has focused on efforts to promote the biological activities of high-density lipoproteins (HDL) in order to reduce cardiovascular risk. Targeting apolipoprotein A-I (apoA-I), the major protein carried on HDL particles, represents an attractive approach to promoting HDL by virtue of its ability to increase endogenous synthesis of functional HDL particles. A number of pharmacological strategies that target apoA-I, including upregulation of its production with the bromodomain and extraterminal (BET) protein inhibitor RVX-208, development of short peptide sequences that mimic its action, and administration as a component of reconstituted HDL particles, have undergone clinical development. The impact of these approaches on cardiovascular biomarkers will be reviewed.

  7. Heparin promotes fibril formation by the N-terminal fragment of amyloidogenic apolipoprotein A-I.

    PubMed

    Mikawa, Shiho; Mizuguchi, Chiharu; Nishitsuji, Kazuchika; Baba, Teruhiko; Shigenaga, Akira; Shimanouchi, Toshinori; Sakashita, Naomi; Otaka, Akira; Akaji, Kenichi; Saito, Hiroyuki

    2016-10-01

    Glycosaminoglycans are known to be associated with extracellular amyloid deposits of various amyloidogenic proteins. In this study, we found that the glycosaminoglycan heparin greatly accelerates the elongation step in fibril formation by the N-terminal 1-83 fragment of human apolipoprotein A-I (apoA-I), especially in the amyloidogenic W50R variant. Using fragment peptides, we demonstrate that heparin significantly promotes β-transition and fibril formation of the highly amyloidogenic region spanning residues 44-65 and colocalizes with fibrils formed by the W50R variant. These results suggest the possible role of glycosaminoglycans in fibril formation by amyloidogenic apoA-I variants. © 2016 Federation of European Biochemical Societies.

  8. Membrane effects of N-terminal fragment of apolipoprotein A-I: a fluorescent probe study.

    PubMed

    Trusova, Valeriya; Gorbenko, Galyna; Girych, Mykhailo; Adachi, Emi; Mizuguchi, Chiharu; Sood, Rohit; Kinnunen, Paavo; Saito, Hiroyuki

    2015-03-01

    The binding of monomeric and aggregated variants of 1-83 N-terminal fragment of apolipoprotein A-I with substitution mutations G26R, G26R/W@8, G26R/W@50 and G26R/W@72 to the model lipid membranes composed of phosphatidylcholine and its mixture with cholesterol has been investigated using fluorescent probes pyrene and Laurdan. Examination of pyrene spectral behavior did not reveal any marked influence of apoA-I mutants on the hydrocarbon region of lipid bilayer. In contrast, probing the membrane effects by Laurdan revealed decrease in the probe generalized polarization in the presence of aggregated proteins. suggesting that oligomeric and fibrillar apoA-I species induce increase in hydration degree and reduction of lipid packing density in the membrane interfacial region. These findings may shed light on molecular details of amyloid cytotoxicity.

  9. Formation of stable nanodiscs by bihelical apolipoprotein A-I mimetic peptide.

    PubMed

    Kariyazono, Hirokazu; Nadai, Ryo; Miyajima, Rin; Takechi-Haraya, Yuki; Baba, Teruhiko; Shigenaga, Akira; Okuhira, Keiichiro; Otaka, Akira; Saito, Hiroyuki

    2016-02-01

    Nanodiscs are composed of scaffold protein or peptide such as apolipoprotein A-I (apoA-I) and phospholipids. Although peptide-based nanodiscs have an advantage to modulate the size of nanodiscs by changing phospholipid/peptide ratios, they are usually less stable than apoA-I-based nanodiscs. In this study, we designed a novel nanodisc scaffold peptide (NSP) that has proline-punctuated bihelical amphipathic structure based on apoA-I mimetic peptides. NSP formed α-helical structure on 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) nanodiscs prepared by cholate dialysis method. Dynamic light scattering measurements demonstrated that diameters of NSP nanodiscs vary depending upon POPC/NSP ratios. Comparison of thermal unfolding of nanodiscs monitored by circular dichroism measurements demonstrated that NSP forms much more stable nanodiscs with POPC than monohelical peptide, 4F, exhibiting comparable stability to apoA-I-POPC nanodiscs. Intrinsic Trp fluorescence measurements showed that Trp residues of NSP exhibit more hydrophobic environment than that of 4 F on nanodiscs, suggesting the stronger interaction of NSP with phospholipids. Thus, the bihelical structure of NSP appears to increase the stability of nanodiscs because of the enhanced interaction of peptides with phospholipids. In addition, NSP as well as 4F spontaneously solubilized POPC vesicles into nanodiscs without using detergent. These results indicate that bihelical NSP forms nanodiscs with comparable stability to apoA-I and has an ability to control the size of nanodiscs simply by changing phospholipid/peptide ratios. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  10. Immunolocalization of cubilin, megalin, apolipoprotein J, and apolipoprotein A-I in the uterus and oviduct.

    PubMed

    Argraves, W Scott; Morales, Carlos R

    2004-12-01

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

  11. Abdominal obesity with hypertriglyceridaemia, lipoprotein(a) and apolipoprotein A-I determine marked cardiometabolic risk.

    PubMed

    Onat, Altan; Can, Günay; Örnek, Ender; Sansoy, Vedat; Aydın, Mesut; Yüksel, Hüsniye

    2013-11-01

    Risks for coronary heart disease (CHD) and diabetes (T2DM) of the 'hypertriglyceridemic waist' phenotype (HtgW) warrant further investigation. We studied this issue and whether partial proinflammatory conversion of apolipoprotein (apo) A-I by lipoprotein(a) [Lp(a)] is a codeterminant. In a population-based prospective study, 1328 Turkish adults were analysed in four groups by the presence of abdominal obesity and elevated triglycerides (Htg). LDL-cholesterol levels, significantly elevated in isolated Htg, were lower in HtgW, yet significantly higher apoB and complement C3 values existed in women with HtgW in whom also the lowest Lp(a) values prevailed. Lp(a) was linearly associated, more strongly in HtgW than in the remaining groups, with apoB and, in women inversely, with gamma-glutamyltransferase. Incident HtgW was predicted, not in men, but in women inversely by Lp(a) (OR 0.80 [95%CI 0.65; 0.97]), regardless of adjustment for relevant confounders. After adjustment for conventional risk factors, HtgW (OR 2.84) and high apoA-I/HDL-C ratio (OR 1.50) were significantly and additively associated with combined prevalent and incident CHD risk. High apoA-I and low HDL-cholesterol levels interacted therein in women. Type-2 diabetes was strongly predicted by HtgW, mediated in men by high apoA-I/HDL-C ratio. HtgW is associated with excess inflammatory markers, is predicted in women paradoxically by lower circulating Lp(a) and is associated in both sexes with marked excess cardiometabolic risk to which high apoA-I/HDL-C ratio contributes additively. These findings are consistent in women with apoA-I being oxidized via aggregation to Lp(a). © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  12. Small business innovation, research & development

    SciTech Connect

    Colvin, D.P.

    1995-12-31

    Historically, small businesses have been the innovation engine of the United States (US). The author provides statistical data that indicates that small business is really big business in the U.S. Small businesses are responsible for much of the applied research necessary for new product development. The author examines productivity, academic research and teaming as a cost-effective and time effective way to develop new products and technologies.

  13. Small Wind Site Assessment Guidelines

    SciTech Connect

    Olsen, Tim; Preus, Robert

    2015-09-01

    Site assessment for small wind energy systems is one of the key factors in the successful installation, operation, and performance of a small wind turbine. A proper site assessment is a difficult process that includes wind resource assessment and the evaluation of site characteristics. These guidelines address many of the relevant parts of a site assessment with an emphasis on wind resource assessment, using methods other than on-site data collection and creating a small wind site assessment report.

  14. Small Particle Scattering and Absorption

    DTIC Science & Technology

    1989-07-01

    hybrid results of close coupling with internal vibrational and other wave modes. Within particles 13 small compared to the free space wavelength these...PROJECT TASK WORK UNIT ELEMENT NO. NO. NO. ACCESSION NO. Aberdeen Proving Ground, MD 21C10-5423 11. TITLE (Include Security Classification) Small ...computational research on electromagnetic scattering by small particles accomplished at the University of Michigan on CRDEC contract DAAA15-86-K-0022

  15. Patient Safety Outcomes in Small Urban and Small Rural Hospitals

    ERIC Educational Resources Information Center

    Vartak, Smruti; Ward, Marcia M.; Vaughn, Thomas E.

    2010-01-01

    Purpose: To assess patient safety outcomes in small urban and small rural hospitals and to examine the relationship of hospital and patient factors to patient safety outcomes. Methods: The Nationwide Inpatient Sample and American Hospital Association annual survey data were used for analyses. To increase comparability, the study sample was…

  16. Small white matter lesion detection in cerebral small vessel disease

    NASA Astrophysics Data System (ADS)

    Ghafoorian, Mohsen; Karssemeijer, Nico; van Uden, Inge; de Leeuw, Frank E.; Heskes, Tom; Marchiori, Elena; Platel, Bram

    2015-03-01

    Cerebral small vessel disease (SVD) is a common finding on magnetic resonance images of elderly people. White matter lesions (WML) are important markers for not only the small vessel disease, but also neuro-degenerative diseases including multiple sclerosis, Alzheimer's disease and vascular dementia. Volumetric measurements such as the "total lesion load", have been studied and related to these diseases. With respect to SVD we conjecture that small lesions are important, as they have been observed to grow over time and they form the majority of lesions in number. To study these small lesions they need to be annotated, which is a complex and time-consuming task. Existing (semi) automatic methods have been aimed at volumetric measurements and large lesions, and are not suitable for the detection of small lesions. In this research we established a supervised voxel classification CAD system, optimized and trained to exclusively detect small WMLs. To achieve this, several preprocessing steps were taken, which included a robust standardization of subject intensities to reduce inter-subject intensity variability as much as possible. A number of features that were found to be well identifying small lesions were calculated including multimodal intensities, tissue probabilities, several features for accurate location description, a number of second order derivative features as well as multi-scale annular filter for blobness detection. Only small lesions were used to learn the target concept via Adaboost using random forests as its basic classifiers. Finally the results were evaluated using Free-response receiver operating characteristic.

  17. Patient Safety Outcomes in Small Urban and Small Rural Hospitals

    ERIC Educational Resources Information Center

    Vartak, Smruti; Ward, Marcia M.; Vaughn, Thomas E.

    2010-01-01

    Purpose: To assess patient safety outcomes in small urban and small rural hospitals and to examine the relationship of hospital and patient factors to patient safety outcomes. Methods: The Nationwide Inpatient Sample and American Hospital Association annual survey data were used for analyses. To increase comparability, the study sample was…

  18. Blood serum apolipoproteins B and A-I in females suffering from rheumatic heart valve disease.

    PubMed

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

    2004-01-01

    With the aim to check whether the atherogenic factors are involved in the mechanisms of valve fibrosis, we have studied the blood serum concentrations of apolipoproteins (apo) A-I and B concentration in patients suffering from rheumatic heart valve fibrosis. The quantities of apoA-I and apoB in the blood serum were tested by the ELISA method. Concentration of apoA-I and B in the blood serum was determined in rheumatic females with replacement of the damaged valves: after aortic valve operation (n=11; mean age 43.3+/-3.6 years) and after mitral valve operation (n=29; 41.3+/-4.1). The results obtained for rheumatic patients were compared with the data on age-matched healthy females (n=43; 39.5+/-5.2 years). Significantly lower apoA-I level in the blood serum of all patients suffering from rheumatic heart valve disease was determined as compared with controls: in the pooled group of patients (1.02+/-0.22 vs 1.23+/-0.23 g/l, P<0.001), in women after aortic valve replacement (0.98+/-0.21 vs. 1.23+/-0.23 g/l, P<0.005), and in women after mitral valve surgery (1.03+/-0.23 g/l vs 1.23+/-0.23 g/l, P<0.005). The apoB level in patients suffering from rheumatic heart valve disease did not differ from that of controls. The apoB/apoA-I ratio for patients with valve fibrotic damage was significantly higher as compared to controls in all groups (P<0.02). The increase of apoB/apoA-I ratio in patients with rheumatic valve fibrosis was caused by lower apoA-I levels in blood serum. The obtained results indicate that decreased apoA-I levels in blood serum can be indicative of valve fibrosis in rheumatic heart valve disease patients.

  19. Molecules that mimic apolipoprotein A-I: potential agents for treating atherosclerosis.

    PubMed

    Leman, Luke J; Maryanoff, Bruce E; Ghadiri, M Reza

    2014-03-27

    Certain amphipathic α-helical peptides can functionally mimic many of the properties of full-length apolipoproteins, thereby offering an approach to modulate high-density lipoprotein (HDL) for combating atherosclerosis. In this Perspective, we summarize the key findings and advances over the past 25 years in the development of peptides that mimic apolipoproteins, especially apolipoprotein A-I (apoA-I). This assemblage of information provides a reasonably clear picture of the state of the art in the apolipoprotein mimetic field, an appreciation of the potential for such agents in pharmacotherapy, and a sense of the opportunities for optimizing the functional properties of HDL.

  20. Molecules that Mimic Apolipoprotein A-I: Potential Agents for Treating Atherosclerosis

    PubMed Central

    Leman, Luke J.; Maryanoff, Bruce E.; Ghadiri, M. Reza

    2013-01-01

    Certain amphipathic α-helical peptides can functionally mimic many of the properties of full-length apolipoproteins, thereby offering an approach to modulate high-density lipoprotein (HDL) for combating atherosclerosis. In this Perspective, we summarize the key findings and advances over the past 25 years in the development of peptides that mimic apolipoproteins, especially apolipoprotein A-I (apoA-I). This assemblage of information provides a reasonably clear picture of the state of the art in the apolipoprotein mimetic field, an appreciation of the potential for such agents in pharmacotherapy, and a sense of the opportunities for optimizing the functional properties of HDL. PMID:24168751

  1. Small Business at EPA Bulletin

    EPA Pesticide Factsheets

    A list of monthly bulletins that highlight information on Agency activities, rulemakings, and to share information about ongoing initiatives from the State Small Business Environmental Assistance Programs.

  2. Small Scarp Close-up

    NASA Image and Video Library

    2015-03-16

    Images obtained after lowering MESSENGER's altitude have revealed a population of small fault scarps (white arrows) that can be more than an order of magnitude smaller in size than their larger counterparts, like Enterprise Rupes. These small scarps are less than 10 km in length and have only tens of meters of relief. They are comparable in size and morphology to small fault scarps imaged on the Moon by the Lunar Reconnaissance Orbiter, suggesting that these small scarps are relatively young, and raising the possibility that some are even active today. http://photojournal.jpl.nasa.gov/catalog/PIA19245

  3. Enhanced HDL Functionality in Small HDL Species Produced Upon Remodeling of HDL by Reconstituted HDL, CSL112

    PubMed Central

    Didichenko, Svetlana A.; Navdaev, Alexei V.; Cukier, Alexandre M.O.; Gille, Andreas; Schuetz, Patrick; Spycher, Martin O.; Thérond, Patrice; Chapman, M. John; Kontush, Anatol

    2016-01-01

    Rationale: CSL112, human apolipoprotein A-I (apoA-I) reconstituted with phosphatidylcholine, is known to cause a dramatic rise in small high-density lipoprotein (HDL). Objective: To explore the mechanisms by which the formation of small HDL particles is induced by CSL112. Methods and Results: Infusion of CSL112 into humans caused elevation of 2 small diameter HDL fractions and 1 large diameter fraction. Ex vivo studies showed that this remodeling does not depend on lipid transfer proteins or lipases. Rather, interaction of CSL112 with purified HDL spontaneously gave rise to 3 HDL species: a large, spherical species composed of apoA-I from native HDL and CSL112; a small, disc-shaped species composed of apoA-I from CSL112, but smaller because of the loss of phospholipids; and the smallest species, lipid-poor apoA-I composed of apoA-I from HDL and CSL112. Time-course studies suggest that remodeling occurs by an initial fusion of CSL112 with HDL and subsequent fission leading to the smaller forms. Functional studies showed that ATP-binding cassette transporter 1–dependent cholesterol efflux and anti-inflammatory effects in whole blood were carried by the 2 small species with little activity in the large species. In contrast, the ability to inactivate lipid hydroperoxides in oxidized low-density lipoprotein was carried predominantly by the 2 largest species and was low in lipid-poor apoA-I. Conclusions: We have described a mechanism for the formation of small, highly functional HDL species involving spontaneous fusion of discoidal HDL with spherical HDL and subsequent fission. Similar remodeling is likely to occur during the life cycle of apoA-I in vivo. PMID:27436846

  4. The Concentration of Apolipoprotein A-I Decreases during Experimentally Induced Acute-Phase Processes in Pigs

    PubMed Central

    Carpintero, R.; Piñeiro, M.; Andrés, M.; Iturralde, M.; Alava, M. A.; Heegaard, P. M. H.; Jobert, J. L.; Madec, F.; Lampreave, F.

    2005-01-01

    In this work, apolipoprotein A-I (ApoA-I) was purified from pig sera. The responses of this protein after sterile inflammation and in animals infected with Actinobacillus pleuropneumoniae or Streptococcus suis were investigated. Decreases in the concentrations of ApoA-I, two to five times lower than the initial values, were observed at 2 to 4 days. It is concluded that ApoA-I is a negative acute-phase protein in pigs. PMID:15845530

  5. Small Molecular as SIRT Modulators.

    PubMed

    Yao, Lei; Xu, Xiangming; Chen, Kai

    2016-06-19

    Sirtuins are class III histone deacetylases, they involve in many important biological functions. Small molecules that can modulate sirtuin activity have been shown to have potential for treating many human diseases. In the article, recent development of small molecular as SIRT modulators has been reviewed.

  6. Benthic invertebrate fauna, small streams

    Treesearch

    J. Bruce Wallace; S.L. Eggert

    2009-01-01

    Small streams (first- through third-order streams) make up >98% of the total number of stream segments and >86% of stream length in many drainage networks. Small streams occur over a wide array of climates, geology, and biomes, which influence temperature, hydrologic regimes, water chemistry, light, substrate, stream permanence, a basin's terrestrial plant...

  7. The Big Benefits of Smallness.

    ERIC Educational Resources Information Center

    Meier, Deborah W.

    1996-01-01

    Small schools (300 to 400 students) offer a real panacea for America's educational ills. New York City's celebrated Central Park East schools lack separate buildings, but have the climate and culture for developing democratic habits of heart and mind. Smallness can facilitate governance, respect, simplicity, safety, parent involvement,…

  8. Individual and Small Group Territories

    ERIC Educational Resources Information Center

    Edney, Julian J.; Uhlig, Susan R.

    1977-01-01

    Explores the reactions of single persons and small groups-each in a room they had territorialized- and to compare these against the reactions of singles and small groups who were in a comparable room which they had not territorialized. (Author)

  9. Small Gas Turbine Engine Technology

    DTIC Science & Technology

    1991-01-01

    Highly advanced small turbine engines will require novel and innovative concepts that minimize the cost and complexity of variable geometry if full...Enhanced computational tools development, verification and application to advanced concepts are rsquired to provide highly advanced, effi- cient... concepts . 3 EFFICIENT ENGINE CYCLES Small vs. large. - Previous investments in technology programs by govern- ment and industry have led to significant

  10. Small Moon Makes Big Waves

    NASA Image and Video Library

    2012-12-31

    Saturn small moon Daphnis is caught in the act of raising waves on the edges of the Keeler gap, which is the thin dark band in the left half of the image. Waves like these allow scientists to locate small moons in gaps and measure their masses.

  11. Financial management for small companies

    Treesearch

    Bruce Hansen; Jeff Palmer; Jeff Palmer

    2000-01-01

    The wood-products industry is characterized by many small manufacturers that lack the staff to compile and analyze information on their operations and investments. Two computer programs, FRAN and JEFFI, have been developed by the USDA Forest Service at Princeton, West Virginia,to help small companies better analyze and monitor current performance, and better evaluate...

  12. Resourcing Change in Small Schools

    ERIC Educational Resources Information Center

    Anderson, Michelle; White, Simone

    2011-01-01

    The theme of this article is the challenge that school leaders face in creating the conditions for learning in small schools. We draw on the concepts of "social capital" and "social entrepreneurship" to identify tensions and possibilities for school leaders in a case study of a small rural school as they seek to find resources…

  13. Role Transitions in Small Groups.

    ERIC Educational Resources Information Center

    Moreland, Richard L.; Levine, John M.

    This paper analyzes role transitions in small groups within the context of a more general model of group socialization that is based on the psychological processes of evaluation, commitment, and decision making. The major advantage of such an approach is that it specifies why role transitions in small groups occur. According to the model, groups…

  14. [Pain therapy in small pets].

    PubMed

    Tacke, Sabine; Gollwitzer, Andrea; Grammel, Lukas; Henke, Julia

    2017-02-09

    Although many advances in pain therapy have been made in recent years, pain therapy is more difficult in the small domestic animal than in cats and dogs. However, there is the ethical obligation that these animals also receive adequate pain therapy. An analgesic is rarely authorized for use in small pets, with pharmacological investigations often lacking and dosages frequently only determined empirically. The small size of the animals often requires a higher dose per kilogram bodyweight compared to cats and dogs. The dosage itself is also difficult to apply in small animals, because many analgesics must be diluted before their use. In addition, frequent manipulation of small animals for analgesic administration induces stress in the patient, which can intensify the pain. In the present article, those analgesics suitable for use in the small domestic animal are described and the indications for the use of the various types of analgesics are explained. A specialized section concentrates on pain detection and algesimetry in the small domestic animal. The detection of pain is much more difficult in small domestic animals. In the last few years so-called "grimace scales" have been developed which are used to assess the facial expression of the animals.

  15. 22 CFR 214.31 - A.I.D. Advisory Committee Representative.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... MANAGEMENT Operation of Advisory Committees § 214.31 A.I.D. Advisory Committee Representative. (a) For each... with the Advisory Committee Management Officer and the General Counsel for decisions by the... Advisory Committee Management Officer. (5) Assuring that open meetings are accessible to the public; (6) As...

  16. 22 CFR 214.31 - A.I.D. Advisory Committee Representative.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... MANAGEMENT Operation of Advisory Committees § 214.31 A.I.D. Advisory Committee Representative. (a) For each... with the Advisory Committee Management Officer and the General Counsel for decisions by the... Advisory Committee Management Officer. (5) Assuring that open meetings are accessible to the public; (6) As...

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

    PubMed

    Cheng, B

    1993-08-01

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

  18. Docosahexaenoic acid suppresses apolipoprotein A-I gene expression through hepatocyte nuclear factor-3beta

    USDA-ARS?s Scientific Manuscript database

    BACKGROUND: Dietary fish-oil supplementation has been shown in human kinetic studies to lower the production rate of apolipoprotein (apo) A-I, the major protein component of HDL. The underlying mechanism responsible for this effect is not fully understood. OBJECTIVE: We investigated the effect and...

  19. [To the history of Tretiyakov almshouse of the A.I. Vishnevskiy Institute of Surgery].

    PubMed

    Kuzybayeva, M P

    2014-01-01

    The article deals with reconstruction of history of building and functioning of Tretiyakov almshouse in the A.I. Vishnevskiy institute of surgery. The archive documents were used for exploration. The input of architect S.I. Soloviyev into formation of architectural complex is demonstrated. The significance of this object in the history of national architecture is established.

  20. Ictalurus punctatus apolipoprotein A-I (ApoA1) mRNA, complete cds

    USDA-ARS?s Scientific Manuscript database

    The complete coding sequence of channel catfish apolipoprotein A-I is 777 bp in length, encoding 258 amino acids. The publishing of this coding sequence will also allow phylogenetic comparison between catfish ApoAI and ApoAI genes from other species. The availability of this complete coding sequence...

  1. 22 CFR 214.31 - A.I.D. Advisory Committee Representative.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... MANAGEMENT Operation of Advisory Committees § 214.31 A.I.D. Advisory Committee Representative. (a) For each... with the Advisory Committee Management Officer and the General Counsel for decisions by the... Advisory Committee Management Officer. (5) Assuring that open meetings are accessible to the public; (6)...

  2. Small pixel infrared sensor technology

    NASA Astrophysics Data System (ADS)

    Caulfield, John; Curzan, Jon

    2017-02-01

    We report on product maturation of small pixel high definition high charge capacity 2.4 Mpixel MWIR Infrared Focal Plane Arrays. This high definition (HD) FPA utilizes a small 5 um pitch pixel size which enables near Nyquist limited sampling with by the optical system of many IR lenses. These smaller sub diffraction pitch pixels enable improved sensitivity and resolution resulting in clear, crisp high contrast imaging with excellent IFOVs even with small focal length lenses. The small pixel IR sensor allows the designer to trade off field of view, MTF, optics F/# to obtain a more compact and high performance IR sensor. This enables lower size, power and weight reductions of the entire IR Sensor System. The highly sensitive MWIR small pixel HD FPA has the capability to detect dimmer signals at longer ranges than previously demonstrated.

  3. Small bowel obstruction- a surprise.

    PubMed

    Mathew, Jeffrey Daniel; Cp, Ganesh Babu; M, Balachandar; M, Ramanathan

    2015-01-01

    Trans - omental hernia is very rare, accounting to 1-4% of all internal hernias which is an unusual cause of small bowel obstruction. Here we present a case report of a small bowel obstruction in a female due to trans - omental hernia presenting with central abdominal pain, distension and bilious vomiting. She had no previous history of trauma, surgery. Plain X-ray abdomen erect showed multiple air fluid levels with dilated small bowel loops. Emergency laparotomy revealed a segment of congested small bowel loop (ileum) through a defect in greater omentum. On table the herniated bowel loop was reduced and the defect in greater omentum was closed primarily. There was no necessity for bowel resection as it regained normal colour after reduction. Postoperative period was uneventful with complete resolution of symptoms. This case is presented for its rarity and its importance in clinical differential diagnosis of acute abdomen due to small bowel obstruction.

  4. Small dams need better management

    NASA Astrophysics Data System (ADS)

    Balcerak, Ernie

    2012-03-01

    Many small dams around the world are poorly maintained and represent a safety hazard, according to Pisaniello et al. Better oversight of small dams is needed, the authors argue. The researchers reviewed literature, conducted case studies in four states in Australia, and developed policy benchmarks and best practices for small-dam management. Small dams, often just several meters high and typically privately owned by individual farmers, have historically caused major damage when they fail. For instance, in China in 1975, 230,000 people died when two large dams failed because of the cumulative failure of 60 smaller upstream dams. In the United States, in 1977 the 8-meter-high Kelly Barnes Lake dam failed, killing 39 people. Many other small-dam failures around the world have resulted in casualties and severe ecological and economic damage.

  5. Apolipoprotein A-I mimetic peptide reverses impaired arterial healing after injury by reducing oxidative stress.

    PubMed

    Rosenbaum, Michael A; Chaudhuri, Pinaki; Abelson, Benjamin; Cross, Brandy N; Graham, Linda M

    2015-08-01

    Endothelial cell (EC) migration is essential for healing of arterial injuries caused by angioplasty, but a high cholesterol diet inhibits endothelial repair. In vivo studies suggest that apolipoprotein A-I (apoA-I), the major protein constituent of HDL, is essential for normal healing of arterial injuries. ApoA-I mimetics, including 4F, have been designed to mimic the amphipathic portion of the apoA-I molecule. This study was undertaken to determine if 4F improves endothelial migration and healing. A razor scrape assay was used to analyze the effect of 4F on EC migration in vitro. Endothelial healing in vivo was assessed following electrical injury of carotid arteries in mice. Markers of oxidative stress were also examined. Lipid oxidation products inhibited EC migration in vitro, but preincubation with L-4F preserved EC migration. Endothelial healing of carotid arterial injuries in mice on a high cholesterol diet was delayed compared with mice on a chow diet with 27.8% vs. 48.2% healing, respectively, at 5 days. Administration of D-4F improved endothelial healing in mice on a high cholesterol diet to 43.4%. D-4F administration had no effect on lipid levels but decreased markers of oxidation. In vivo, there was a significant inverse correlation between endothelial healing and plasma markers of oxidative stress. These studies suggested that an apoA-I mimetic can improve endothelial healing of arterial injuries by decreasing oxidative stress. Published by Elsevier Ireland Ltd.

  6. Transcriptome-wide identification of A > I RNA editing sites by inosine specific cleavage

    PubMed Central

    Cattenoz, Pierre B.; Taft, Ryan J.; Westhof, Eric; Mattick, John S.

    2013-01-01

    Adenosine to inosine (A > I) RNA editing, which is catalyzed by the ADAR family of proteins, is one of the fundamental mechanisms by which transcriptomic diversity is generated. Indeed, a number of genome-wide analyses have shown that A > I editing is not limited to a few mRNAs, as originally thought, but occurs widely across the transcriptome, especially in the brain. Importantly, there is increasing evidence that A > I editing is essential for animal development and nervous system function. To more efficiently characterize the complete catalog of ADAR events in the mammalian transcriptome we developed a high-throughput protocol to identify A > I editing sites, which exploits the capacity of glyoxal to protect guanosine, but not inosine, from RNAse T1 treatment, thus facilitating extraction of RNA fragments with inosine bases at their termini for high-throughput sequencing. Using this method we identified 665 editing sites in mouse brain RNA, including most known sites and suite of novel sites that include nonsynonymous changes to protein-coding genes, hyperediting of genes known to regulate p53, and alterations to non-protein-coding RNAs. This method is applicable to any biological system for the de novo discovery of A > I editing sites, and avoids the complicated informatic and practical issues associated with editing site identification using traditional RNA sequencing data. This approach has the potential to substantially increase our understanding of the extent and function of RNA editing, and thereby to shed light on the role of transcriptional plasticity in evolution, development, and cognition. PMID:23264566

  7. HDL-apolipoprotein A-I exchange is independently associated with cholesterol efflux capacity.

    PubMed

    Borja, Mark S; Ng, Kit F; Irwin, Angela; Hong, Jaekyoung; Wu, Xing; Isquith, Daniel; Zhao, Xue-Qiao; Prazen, Bryan; Gildengorin, Virginia; Oda, Michael N; Vaisar, Tomáš

    2015-10-01

    HDL is the primary mediator of cholesterol mobilization from the periphery to the liver via reverse cholesterol transport (RCT). A critical first step in this process is the uptake of cholesterol from lipid-loaded macrophages by HDL, a function of HDL inversely associated with prevalent and incident cardiovascular disease. We hypothesized that the dynamic ability of HDL to undergo remodeling and exchange of apoA-I is an important and potentially rate-limiting aspect of RCT. In this study, we investigated the relationship between HDL-apoA-I exchange (HAE) and serum HDL cholesterol (HDL-C) efflux capacity. We compared HAE to the total and ABCA1-specific cholesterol efflux capacity of 77 subjects. We found that HAE was highly correlated with both total (r = 0.69, P < 0.0001) and ABCA1-specific (r = 0.47, P < 0.0001) efflux, and this relationship remained significant after adjustment for HDL-C or apoA-I. Multivariate models of sterol efflux capacity indicated that HAE accounted for approximately 25% of the model variance for both total and ABCA1-specific efflux. We conclude that the ability of HDL to exchange apoA-I and remodel, as measured by HAE, is a significant contributor to serum HDL efflux capacity, independent of HDL-C and apoA-I, indicating that HDL dynamics are an important factor in cholesterol efflux capacity and likely RCT. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

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

    SciTech Connect

    Orlov, Sergey V.; Mogilenko, Denis A.; Shavva, Vladimir S.; Dizhe, Ella B.; Ignatovich, Irina A.; Perevozchikov, Andrej P.

    2010-07-23

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

  9. Tamarindus indica extract alters release of alpha enolase, apolipoprotein A-I, transthyretin and Rab GDP dissociation inhibitor beta from HepG2 cells.

    PubMed

    Chong, Ursula Rho Wan; Abdul-Rahman, Puteri Shafinaz; Abdul-Aziz, Azlina; Hashim, Onn Haji; Junit, Sarni Mat

    2012-01-01

    The plasma cholesterol and triacylglycerol lowering effects of Tamarindus indica extract have been previously described. We have also shown that the methanol extract of T. indica fruit pulp altered the expression of lipid-associated genes including ABCG5 and APOAI in HepG2 cells. In the present study, effects of the same extract on the release of proteins from the cells were investigated using the proteomics approach. When culture media of HepG2 cells grown in the absence and presence of the methanol extract of T. indica fruit pulp were subjected to 2-dimensional gel electrophoresis, the expression of seven proteins was found to be significantly different (p<0.03125). Five of the spots were subsequently identified as alpha enolase (ENO1), transthyretin (TTR), apolipoprotein A-I (ApoA-I; two isoforms), and rab GDP dissociation inhibitor beta (GDI-2). A functional network of lipid metabolism, molecular transport and small molecule biochemistry that interconnects the three latter proteins with the interactomes was identified using the Ingenuity Pathways Analysis software. The methanol extract of T. indica fruit pulp altered the release of ENO1, ApoA-I, TTR and GDI-2 from HepG2 cells. Our results provide support on the effect of T. indica extract on cellular lipid metabolism, particularly that of cholesterol.

  10. Retrospective analysis of NRECA's (National Rural Electric Cooperative Association) activities with A. I. D. funding 1962-1981

    SciTech Connect

    Not Available

    1981-01-01

    Rural electrification (RE) has proven to be one of A.I.D.'s most effective responses to Congressional mandates to serve the poor and do so through cooperatives when possible. This report overviews the National Rural Electric Cooperative Associations (NRECA) 20-year experience in providing developing countries with A.I.D.-financed technical assistance and training; examines NRECA-A.I.D. relationships; provides examples of NRECA's performance in 17 countries; briefly describes non-A.I.D. NRECA projects; and identifies opportunities for NRECA and A.I.D. to jointly undertake a broader range of energy-related activities in the future.

  11. Small-world brain networks.

    PubMed

    Bassett, Danielle Smith; Bullmore, Ed

    2006-12-01

    Many complex networks have a small-world topology characterized by dense local clustering or cliquishness of connections between neighboring nodes yet a short path length between any (distant) pair of nodes due to the existence of relatively few long-range connections. This is an attractive model for the organization of brain anatomical and functional networks because a small-world topology can support both segregated/specialized and distributed/integrated information processing. Moreover, small-world networks are economical, tending to minimize wiring costs while supporting high dynamical complexity. The authors introduce some of the key mathematical concepts in graph theory required for small-world analysis and review how these methods have been applied to quantification of cortical connectivity matrices derived from anatomical tract-tracing studies in the macaque monkey and the cat. The evolution of small-world networks is discussed in terms of a selection pressure to deliver cost-effective information-processing systems. The authors illustrate how these techniques and concepts are increasingly being applied to the analysis of human brain functional networks derived from electroencephalography/magnetoencephalography and fMRI experiments. Finally, the authors consider the relevance of small-world models for understanding the emergence of complex behaviors and the resilience of brain systems to pathological attack by disease or aberrant development. They conclude that small-world models provide a powerful and versatile approach to understanding the structure and function of human brain systems.

  12. Apolipoprotein A-I assayed in human serum by isotope dilution as a potential standard for immunoassay

    SciTech Connect

    Weech, P.K.; Jewer, D.; Marcel, Y.L.

    1988-01-01

    We measured the amount of apoA-I in serum by isotope dilution, finding 1.33 mg/ml (standard deviation 0.177) in six normolipidemic, healthy subjects. We developed this method by adapting published techniques to purify apoA-I from 3 ml of serum in two steps: density gradient ultracentrifugation and high performance liquid chromatography gel filtration. The 125I-labeled apoA-I tracer was first screened, by incubation with serum, to select labeled apoA-I which retained the ability to exchange with native apoA-I and bind to HDL. A known amount of 125I-labeled apoA-I-labeled HDL was added to unknown serum samples; apoA-I was reisolated from the serum and its specific radioactivity was used to calculate the dilution of the added, labeled apoA-I by the unlabeled apoA-I in the unknown serum. By not relying on immunochemical techniques, the isotope dilution assay provided results that are independent of the expression of individual apoA-I antigenic sites. Therefore, sera that have been assayed by isotope dilution can serve as standards to evaluate the accuracy of immunoassays for serum apoA-I and provide primary standards for such immunoassays.

  13. General Treatment Information for Small Intestine Adenocarcinoma

    MedlinePlus

    ... Cancer A-Z Small Intestine Cancer Treating Small Intestine Cancer General treatment information Depending on the type ... questions about your treatment options. More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  14. Comparative Effects of Diet-Induced Lipid Lowering Versus Lipid Lowering Along With Apo A-I Milano Gene Therapy on Regression of Atherosclerosis.

    PubMed

    Wang, Lai; Tian, Fang; Arias, Ana; Yang, Mingjie; Sharifi, Behrooz G; Shah, Prediman K

    2016-05-01

    Apolipoprotein A-1 (Apo A-I) Milano, a naturally occurring Arg173to Cys mutant of Apo A-1, has been shown to reduce atherosclerosis in animal models and in a small phase 2 human trial. We have shown the superior atheroprotective effects of Apo A-I Milano (Apo A-IM) gene compared to wild-type Apo A-I gene using transplantation of retrovirally transduced bone marrow in Apo A-I/Apo E null mice. In this study, we compared the effect of dietary lipid lowering versus lipid lowering plus Apo A-IM gene transfer using recombinant adeno-associated virus (rAAV) 8 as vectors on atherosclerosis regression in Apo A-I/Apo E null mice. All mice were fed a high-cholesterol diet from age of 6 weeks until week 20, and at 20 weeks, 10 mice were euthanized to determine the extent of atherosclerosis. After 20 weeks, an additional 20 mice were placed on either a low-cholesterol diet plus empty rAAV (n = 10) to serve as controls or low-cholesterol diet plus 1 single intravenous injection of 1.2 × 10(12)vector genomes of adeno-associated virus (AAV) 8 vectors expressing Apo A-IM (n = 10). At the 40 week time point, intravenous AAV8 Apo A-IM recipients showed a significant regression of atherosclerosis in the whole aorta (P< .01), aortic sinuses (P< .05), and brachiocephalic arteries (P< .05) compared to 20-week-old mice, whereas low-cholesterol diet plus empty vector control group showed no significant regression in lesion size. Immunostaining showed that compared to the 20-week-old mice, there was a significantly reduced macrophage content in the brachiocephalic (P< .05) and aortic sinus plaques (P< .05) of AAV8 Apo A-IM recipients. These data show that although dietary-mediated cholesterol lowering halts progression of atherosclerosis, it does not induce regression, whereas combination of low-cholesterol diet and AAV8 mediated Apo A-I Milano gene therapy induces rapid and significant regression of atherosclerosis in mice. These data provide support for the potential feasibility of this

  15. Environmental Justice Small Grants Program

    EPA Pesticide Factsheets

    The Environmental Justice Small Grants Program provides financial assistance to eligible organizations to build collaborative partnerships, to identify the local environmental and/or public health issues, and to envision solutions and empower the community

  16. Small and Rural Wastewater Systems

    EPA Pesticide Factsheets

    Many tools, training, technical assistance, and funding resources are available to develop and maintain reliable and affordable wastewater treatment systems in small and rural communities including in tribal and U.S.-Mexico Border area.

  17. Learn about Small Wastewater Systems

    EPA Pesticide Factsheets

    Many small and rural communities, including those in Indian Country and along the U.S.-Mexico border, struggle with aging or inadequate wastewater treatment systems, or do not have access to basic wastewater services.

  18. Urban Waters Small Grants 101

    EPA Pesticide Factsheets

    General information on Urban Waters Small Grants is provided in this document. Grantees are listed by themes, including Environmental Justice, Water Quality, Job Training and Creation, and Green Infrastructure.

  19. Small Airframe Manufacturer's Icing Perspective

    NASA Technical Reports Server (NTRS)

    Hoppins, Jim

    2009-01-01

    This viewgraph presentation describes the icing effects, risk mitigation practices, and icing certifications for various Cessna small aircraft models. NASA's role in the development of simulation tools for icing certifications is also discussed.

  20. Unsteady swimming of small organisms

    NASA Astrophysics Data System (ADS)

    Wang, Shiyan; Ardekani, Arezoo

    2012-11-01

    Small planktonic organisms ubiquitously display unsteady or impulsive motion to attack a prey or escape a predator in natural environments. Despite this, the role of unsteady hydrodynamic forces such as history and added mass forces on the low Reynolds number propulsion of small organisms is poorly understood. In this paper, we derive the fundamental equation of motion for an organism swimming by the means of surface distortion in a nonuniform flow at a low Reynolds number regime. We show that the history and added mass forces, that where traditionally neglected in the literature for small swimming organisms, cannot be neglected as the Stokes number increases above unity. For example, these unsteady inertial forces are of the same order as quasi-steady Stokes forces for Paramecium. Finally, we quantify the effects of convective inertial forces in the limit of small, but nonzero, Reynolds number regime. This work is supported by NSF grant CBET-1066545.

  1. Small-scale hydropower systems

    SciTech Connect

    Not Available

    1988-04-01

    This report covers several aspects of small-scale hydropower systems. The topics covered are: head and flow; waterwheels; impulse and reaction turbines; feasibility and practicality; environmental impact; and economics. 24 refs., 5 figs. (JF)

  2. Small Specifications for Tree Update

    NASA Astrophysics Data System (ADS)

    Gardner, Philippa; Wheelhouse, Mark

    O'Hearn, Reynolds and Yang introduced Separation Logic to provide modular reasoning about simple, mutable data structures in memory. They were able to construct small specifications of programs, by reasoning about the local parts of memory accessed by programs. Gardner, Calcagno and Zarfaty generalised this work, introducing Context Logic to reason about more complex data structures. In particular, they developed a formal, compositional specification of the Document Object Model, a W3C XML update library. Whilst keeping to the spirit of local reasoning, they were not able to retain small specifications. We introduce Segment Logic, which provides a more fine-grained analysis of the tree structure and yields small specifications. As well as being aesthetically pleasing, small specifications are important for reasoning about concurrent tree update.

  3. Small Solid Rocket Motor Test

    NASA Image and Video Library

    It was three-two-one to brilliant fire as NASA's Marshall Space Flight Center tested a small solid rocket motor designed to mimic NASA's Space Launch System booster. The Mar. 14 test provides a qui...

  4. Small amplitude quasibreathers and oscillons

    SciTech Connect

    Fodor, Gyula; Lukacs, Arpad; Forgacs, Peter; Horvath, Zalan

    2008-07-15

    Quasibreathers (QB) are time-periodic solutions with weak spatial localization introduced in G. Fodor et al. in [Phys. Rev. D 74, 124003 (2006)]. QB's provide a simple description of oscillons (very long-living spatially localized time dependent solutions). The small amplitude limit of QB's is worked out in a large class of scalar theories with a general self-interaction potential, in D spatial dimensions. It is shown that the problem of small amplitude QB's is reduced to a universal elliptic partial differential equation. It is also found that there is the critical dimension, D{sub crit}=4, above which no small amplitude QB's exist. The QB's obtained this way are shown to provide very good initial data for oscillons. Thus these QB's provide the solution of the complicated, nonlinear time dependent problem of small amplitude oscillons in scalar theories.

  5. Small- x resummation from HELL

    NASA Astrophysics Data System (ADS)

    Bonvini, Marco; Marzani, Simone; Peraro, Tiziano

    2016-11-01

    Small- x logarithmic enhancements arising from high-energy gluon emissions affect both the evolution of collinearly-factorized parton densities and partonic coefficient functions. With the higher collider energy reached by the LHC, the prospect of a future high-energy collider, and the recent deep-inelastic scattering (DIS) results at small- x from HERA, providing phenomenological tools for performing small- x resummation has become of great relevance. In this paper we discuss a framework to perform small- x resummation for both parton evolution and partonic coefficient functions and we describe its implementation in a computer code named High-Energy Large Logarithms ( HELL). We present resummed and matched results for the DGLAP splitting functions and, as a proof of principle, for the massless structure functions in DIS. Furthermore, we discuss the uncertainty from subleading terms on our results.

  6. DoD Small Business Innovation Research Program

    DTIC Science & Technology

    2009-01-30

    00-00-2009 to 00-00-2009 4 . TITLE AND SUBTITLE DoD Small Business Innovation Research Program 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...additional comments from the Under Secretary of Defense to Recommendations A.I., A.3., A. 4 ., B.i.a., and B.I.b.; and from the Assistant Secretary of...staff. Questions should be directed to Richard B. Jolliffe at 703604- 9201 . If you desire, we will provide a formal briefing on the results. Ric 1ard B

  7. Ochracenes A-I, Humulane-Derived Sesquiterpenoids from the Antarctic Fungus Aspergillus ochraceopetaliformis.

    PubMed

    Wang, Junfeng; He, Weijun; Kong, Fandong; Tian, Xinpeng; Wang, Pei; Zhou, Xiaojiang; Liu, Yonghong

    2017-06-23

    Nine new humulane-derived sesquiterpenoids, ochracenes A-I (1-9), were isolated from the Antarctic fungus Aspergillus ochraceopetaliformis SCSIO 05702. Their structures including absolute configurations were elucidated on the basis of spectroscopic analysis, Mosher's method, and electronic circular dichroism analysis. Compared with previous humulane-type sesquiterpenoids, ochracenes A-I (1-9) featured novel carbon skeletons with corresponding methyl migration, ring cleavage, and carbon loss. Two unprecedented 8,9-secocyclic sesquiterpenoids (2 and 3) exhibited inhibitory effects on lipopolysaccharide-induced NO release in RAW 264.7 mouse macrophage cell lines with IC50 values of 14.6 ± 0.5 and 18.3 ± 1.7 μM, respectively.

  8. Small bowel and colon perforation.

    PubMed

    Brown, Carlos V R

    2014-04-01

    For patients with small bowel and colonic perforations, a definitive diagnosis of the cause of perforation is not necessary before operation. Bowel obstruction and inflammatory bowel disease are the most common causes of nontraumatic intestinal perforations in industrialized countries, whereas infectious causes of intestinal perforations are more common in developing countries. Treatment of small bowel and colonic perforations generally includes intravenous antibiotics and fluid resuscitation, but the specific management of the bowel depends on the underlying cause of the perforation.

  9. Kinematic Tests of Small Arms

    DTIC Science & Technology

    2016-03-15

    needed measurements can be made. g. In order to make these calculations, software should be able to output these positional values over time into a...other means, and (b) measuring the impulse and recoil of small- caliber weapons by a laser displacement measurement system, HSV, displacement...transducers, or other means. 15. SUBJECT TERMS kinematic, small arms, recoil measurements , laser tracking system 16. SECURITY CLASSIFICATION OF

  10. Spring Small Grains Area Estimation

    NASA Technical Reports Server (NTRS)

    Palmer, W. F.; Mohler, R. J.

    1986-01-01

    SSG3 automatically estimates acreage of spring small grains from Landsat data. Report describes development and testing of a computerized technique for using Landsat multispectral scanner (MSS) data to estimate acreage of spring small grains (wheat, barley, and oats). Application of technique to analysis of four years of data from United States and Canada yielded estimates of accuracy comparable to those obtained through procedures that rely on trained analysis.

  11. 8. Print of a drawing: "Plan No. 24, A.I. No. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Print of a drawing: "Plan No. 24, A.I. No. 00036-A, Bldg. 27 (no date). Probably not of Building 27, but a similar heating installation elsewhere on the fort, or an alternate plan for the building which was never constructed. (8" x 10" print enlarged from 4" x 5" negative.) - Fort Benjamin Harrison, Building No. 27, Otis Avenue east of Green Avenue, Lawrence, Marion County, IN

  12. Apolipoprotein A-I Milano exhibits potent antioxidant activity on phospholipid surfaces

    SciTech Connect

    Bielicki, John K.; Oda, Michael N.

    2001-09-21

    Apolipoprotein(apo)A-IMilano and apoA-IParis are rare cysteine variants of apoA-I that produce a HDL deficiency in the absence of cardiovascular disease in humans. This paradox provides the basis for the hypothesis that the cysteine variants posses a beneficial activity not associated with wild-type apoA-I (apoA-IWT). In this study, a unique antioxidant activity of apoA-IMilano and apoA-IParis is described. Antioxidant activity was observed using the monomeric form of the variants and was equally effective before and after initiation of oxidative events. ApoA-IMilano was twice as effective as apoA-IParis in preventing lipoxygenase-mediated oxidation of phospholipids; whereas, apoA-IWT was poorly active. ApoA-IMilano protected phospholipid from reactive oxygen species (ROS) generated via xanthine/xanthine oxidase (X/Xo) but failed to inhibit X/Xo induced reduction of cytochrome C. These results indicate that (1) the antioxidant activity of apoA-IMilano was dependent on phospholipid and (2) the cysteine variant was unable to directly quench ROS in the aqueous phase. There were no differences between lipid-free apoA-IMilano, apoA-IParis, and apoA-IWT in mediating the efflux of cholesterol from macrophages indicating the cysteine variants interacted normally with the ABCA1 efflux pathway. The results indicate that incorporation of a free thiol within an amphipathic alpha helix of apoA-I confers an antioxidant activity distinct from that of apoA-IWT. These studies are the first to relate addition-of-function to rare cysteine mutations in apoA-I primary sequence.

  13. Severe adhesive small bowel obstruction.

    PubMed

    Di Saverio, Salomone; Catena, Fausto; Kelly, Michael D; Tugnoli, Gregorio; Ansaloni, Luca

    2012-12-01

    Adhesive small bowel obstruction is a frequent cause of hospital admission. Water soluble contrast studies may have diagnostic and therapeutic value and avoid challenging demanding surgical operations, but if bowel ischemia is suspected, prompt surgical intervention is mandatory. A 58-year-old patient was operated for extensive adhesive small bowel obstruction after having had two previous laparotomies for colorectal surgery, and had a complex clinical course with multiple operations and several complications. Different strategies of management have been adopted, including non-operative management with the use of hyperosmolar water soluble contrast medium, multiple surgical procedures, total parenteral nutrition (TPN) support, and finally use of antiadherences icodextrin solution. After 2 years follow-up the patient was doing well without presenting recurrent episodes of adhesive small bowel obstruction. For patients admitted several times for adhesive small bowel obstruction, the relative risk of recurring obstruction increases in relation to the number of prior episodes. Several strategies for non-operative conservative management of adhesive small bowel obstruction have already addressed diagnostic and therapeutic value of hyperosmolar water soluble contrast. According to the most recent evidence-based guidelines, open surgery is the preferred method for surgical treatment of strangulating adhesive small bowel obstruction as well as after failed conservative management. Research interest and clinical evidence are increasing in adhesions prevention. Hyaluronic acid-carboxycellulose membrane and icodextrin may reduce incidence of adhesions.

  14. Chartering Launchers for Small Satellites

    NASA Astrophysics Data System (ADS)

    Hernandez, Daniel

    The question of how to launch small satellites has been solved over the years by the larger launchers offering small satellites the possibility of piggy-backing. Specific fixtures have been developed and commercialized: Arianespace developed the ASAP interface, the USAF studied ESPA, NASA has promoted Shuttle launch possibilities, Russian authorities and companies have been able to find solutions with many different launchers... It is fair to say that most launcher suppliers have worked hard and finally often been able to find solutions to launch most small satellites into orbit. It is also true, however, that most of these small satellites were technology demonstration missions capable of accepting a wide range of orbit and launch characteristics: orbit altitude and inclination, launch date, etc. In some cases the small satellite missions required a well-defined type of orbit and have therefore been obliged to hire a small launcher on which they were the prime passenger. In our paper we would like to propose an additional solution to all these possibilities: launchers could plan well in advance (for example about 3 years), trips to precisely defined orbits to allow potential passengers to organize themselves and be ready on the D-Day. On the scheduled date the chartered launcher goes to the stated orbit while on another date, another chartered launcher goes to another orbit. The idea is to organize departures for space like trains or airplanes leaving on known schedules for known destinations.

  15. Small group discussion: Students perspectives.

    PubMed

    Annamalai, Nachal; Manivel, Rajajeyakumar; Palanisamy, Rajendran

    2015-08-01

    Various alternative methods are being used in many medical colleges to reinforce didactic lectures in physiology. Small group teaching can take on a variety of different tasks such as problem-solving, role play, discussions, brainstorming, and debate. Research has demonstrated that group discussion promotes greater synthesis and retention of materials. The aims of this study were to adopt a problem-solving approach by relating basic sciences with the clinical scenario through self-learning. To develop soft skills, to understand principles of group dynamics, and adopt a new teaching learning methodology. Experimental study design was conducted in Phase I 1(st) year medical students of 2014-2015 batch (n = 120). On the day of the session, the students were grouped into small groups (15 each). The session started with the facilitator starting off the discussion. Feedback forms from five students in each group was taken (n = 40). A five point Likert scale was used ranging from strongly agree to strongly disagree. Data were analyzed using IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp. Our results show that 70% of the students opined that small group discussion were interactive, friendly, innovative, built interaction between teacher and student. Small group discussion increased their thought process and helped them in better communication. The small group discussion was interactive, friendly, and bridged the gap between the teacher and student. The student's communication skills are also improved. In conclusion, small group discussion is more effective than the traditional teaching methods.

  16. Small

    SciTech Connect

    Montoya, Joseph

    2013-07-18

    Representing the Center on Nanostructuring for Efficient Energy Conversion (CNEEC), this document is one of the entries in the Ten Hundred and One Word Challenge. As part of the challenge, the 46 Energy Frontier Research Centers were invited to represent their science in images, cartoons, photos, words and original paintings, but any descriptions or words could only use the 1000 most commonly used words in the English language, with the addition of one word important to each of the EFRCs and the mission of DOE energy. The mission of CNEEC is to understand how nanostructuring can enhance efficiency for energy conversion and solve fundamental cross-cutting problems in advanced energy conversion and storage systems.

  17. Interfacial interactions of ceramide with dimyristoylphosphatidylcholine: impact of the N-acyl chain.

    PubMed

    Holopainen, J M; Brockman, H L; Brown, R E; Kinnunen, P K

    2001-02-01

    The mixing behavior of dimyristoylphosphatidylcholine (DMPC) with either N-palmitoyl-sphingosine (C16:0-ceramide) or N-nervonoyl-sphingosine (C24:1-ceramide) was examined using monomolecular films. While DMPC forms highly elastic liquid-expanded monolayers, both neat C16:0-ceramide and C24:1-ceramide yield stable solid condensed monomolecular films with small areas and low interfacial elasticity. Compression isotherms of mixed C16:0-ceramide/DMPC films exhibit an apparent condensation upon increasing X(cer16:0) at all surface pressures. The average area isobars, coupled with the lack of a liquid-expanded to condensed phase transition as X(cer16:0) is increased, are indicative of immiscibility of the lipids at all surface pressures. In contrast, isobars for C24:1-ceramide/DMPC mixtures show surface pressure-dependent apparent condensation or expansion and surface pressure-area isotherms show a composition and surface pressure-dependent phase transition. This suggests miscibility, albeit non-ideal, of C24:1-ceramide and DMPC in both liquid and condensed surface phases. The above could be verified by fluorescence microscopy of the monolayers and measurements of surface potential, which revealed distinctly different domain morphologies and surface potential values for the DMPC/C16:0- and DMPC/C24:1-ceramide monolayers. Taken together, whereas C16:0-ceramide and DMPC form immiscible pseudo-compounds, C24:1-ceramide and DMPC are partially miscible in both the liquid-expanded and condensed phases, and a composition and lateral pressure-dependent two-phase region is evident between the liquid-expanded and condensed regimes. Our results provide novel understanding of the regulation of membrane properties by ceramides and raise the possibility that ceramides with different acyl groups could serve very different functions in cells, relating to their different physicochemical properties.

  18. Interfacial interactions of ceramide with dimyristoylphosphatidylcholine: impact of the N-acyl chain.

    PubMed Central

    Holopainen, J M; Brockman, H L; Brown, R E; Kinnunen, P K

    2001-01-01

    The mixing behavior of dimyristoylphosphatidylcholine (DMPC) with either N-palmitoyl-sphingosine (C16:0-ceramide) or N-nervonoyl-sphingosine (C24:1-ceramide) was examined using monomolecular films. While DMPC forms highly elastic liquid-expanded monolayers, both neat C16:0-ceramide and C24:1-ceramide yield stable solid condensed monomolecular films with small areas and low interfacial elasticity. Compression isotherms of mixed C16:0-ceramide/DMPC films exhibit an apparent condensation upon increasing X(cer16:0) at all surface pressures. The average area isobars, coupled with the lack of a liquid-expanded to condensed phase transition as X(cer16:0) is increased, are indicative of immiscibility of the lipids at all surface pressures. In contrast, isobars for C24:1-ceramide/DMPC mixtures show surface pressure-dependent apparent condensation or expansion and surface pressure-area isotherms show a composition and surface pressure-dependent phase transition. This suggests miscibility, albeit non-ideal, of C24:1-ceramide and DMPC in both liquid and condensed surface phases. The above could be verified by fluorescence microscopy of the monolayers and measurements of surface potential, which revealed distinctly different domain morphologies and surface potential values for the DMPC/C16:0- and DMPC/C24:1-ceramide monolayers. Taken together, whereas C16:0-ceramide and DMPC form immiscible pseudo-compounds, C24:1-ceramide and DMPC are partially miscible in both the liquid-expanded and condensed phases, and a composition and lateral pressure-dependent two-phase region is evident between the liquid-expanded and condensed regimes. Our results provide novel understanding of the regulation of membrane properties by ceramides and raise the possibility that ceramides with different acyl groups could serve very different functions in cells, relating to their different physicochemical properties. PMID:11159444

  19. Recombinant amyloidogenic domain of ApoA-I: Analysis of its fibrillogenic potential

    SciTech Connect

    Di Gaetano, Sonia; Guglielmi, Fulvio; Arciello, Angela; Mangione, Palma; Monti, Maria; Pagnozzi, Daniela; Raimondi, Sara; Giorgetti, Sofia; Orru, Stefania; Canale, Claudio; Pucci, Piero; Dobson, Christopher M.; Bellotti, Vittorio; Piccoli, Renata . E-mail: piccoli@unina.it

    2006-12-08

    A variety of amyloid diseases are associated with fibrillar aggregates from N-terminal fragments of ApoA-I generated through a largely unexplored multi-step process. The understanding of the molecular mechanism is impaired by the lack of suitable amounts of the fibrillogenic polypeptides that could not be produced by recombinant methods so far. We report the production and the conformational analysis of recombinant ApoA-I 1-93 fragment. Similarly to the polypeptide isolated ex vivo, a pH switch from 7 to 4 induces a fast and reversible conformational transition to a helical state and leads to the identification of a key intermediate in the fibrillogenesis process. Limited proteolysis experiments suggested that the C-terminal region is involved in helix formation. The recombinant polypeptide generates fibrils at pH 4 on a time scale comparable with that of the native fragment. These findings open the way to studies on structural, thermodynamic, and kinetic aspects of ApoA-I fibrillogenesis.

  20. Safe and sustained overexpression of functional apolipoprotein A-I/high-density lipoprotein in apolipoprotein A-I-null mice by muscular adeno-associated viral serotype 8 vector gene transfer.

    PubMed

    Cimmino, Giovanni; Chen, Wei; Speidl, Walter S; Giannarelli, Chiara; Ibanez, Borja; Fuster, Valentin; Hajjar, Roger; Walsh, Christopher E; Badimon, Juan J

    2009-11-01

    High levels of high-density lipoprotein (HDL) have protective effects against atherosclerosis and cardiovascular diseases. The postulated mechanism of action for these benefits is an enhanced reverse cholesterol transport. Apolipoprotein A-I (ApoA-I) is the major protein of HDL. The clinical benefits of raising ApoA-I/HDL have been clearly established by clinical and epidemiological studies. Despite these observations, there are not very effective pharmacological means for raising HDL. ApoA-I gene delivery by viral vectors seems a promising strategy to raise ApoA-I/HDL levels. Sustained gene expression in animals and humans has been attained using adeno-associated viral (AAV) vectors. The aim of the present study was to determine the efficiency, safety, and biological activity of human ApoA-I intramuscularly delivered using an AAV vector in mice. AAV serotype 8 vectors encoding for human ApoA-I transgene were administered intraportally and intramuscularly in ApoA-I- deficient animals. ApoA-I levels were measured every 2 weeks post administration. The effectiveness of the generated HDL was tested in vitro in cholesterol-loaded macrophages. The administration of the vectors resulted in a significant and sustained increase in ApoA-I and HDL plasma levels for up to 16 weeks at similar extent by both routes of administration. Activity of the generated HDL in removal of cholesterol from cholesterol-loaded macrophages was similar in both groups. Our data suggest that intramuscular AAV8-mediated gene transfer of human ApoA-I results in a significant and maintained increase in ApoA-I and functional HDL.

  1. Small Bowel and Liver/Small Bowel Transplantation in Children

    PubMed Central

    Reyes, Jorge; Tzakis, Andreas G.; Todo, Satoru; Nour, Bakr; Starzl, Thomas E.

    2010-01-01

    A clinical trial of intestinal transplantation was initiated at the University of Pittsburgh in May 1990. Eleven children received either a combined liver/small bowel graft (n = 8) or an isolated small bowel graft (n = 3). Induction as well as maintenance immunosuppression was with FK-506 and steroids. Four patients were male, and seven were female; the age range was 6 months to 10.2 years. There were 3 deaths (all in recipients of the combined liver/small bowel graft), which were attributed to graft-versus-host disease (n = 1), posttransplant lymphoproliferative disease (n = 1), and biliary leak (n = 1). Transplantation of the intestine has evolved into a feasible operation, with an overall patient and graft survival rate of 73%. These survivors are free of total parenteral nutrition, and the majority are home. These encouraging results justify further clinical trials. PMID:8062049

  2. Maybe Small Is Too Small a Term: Introduction to Advancing Small Sample Prevention Science.

    PubMed

    Fok, Carlotta Ching Ting; Henry, David; Allen, James

    2015-10-01

    Prevention research addressing health disparities often involves work with small population groups experiencing such disparities. The goals of this special section are to (1) address the question of what constitutes a small sample; (2) identify some of the key research design and analytic issues that arise in prevention research with small samples; (3) develop applied, problem-oriented, and methodologically innovative solutions to these design and analytic issues; and (4) evaluate the potential role of these innovative solutions in describing phenomena, testing theory, and evaluating interventions in prevention research. Through these efforts, we hope to promote broader application of these methodological innovations. We also seek whenever possible, to explore their implications in more general problems that appear in research with small samples but concern all areas of prevention research. This special section includes two sections. The first section aims to provide input for researchers at the design phase, while the second focuses on analysis. Each article describes an innovative solution to one or more challenges posed by the analysis of small samples, with special emphasis on testing for intervention effects in prevention research. A concluding article summarizes some of their broader implications, along with conclusions regarding future directions in research with small samples in prevention science. Finally, a commentary provides the perspective of the federal agencies that sponsored the conference that gave rise to this special section.

  3. Concentration-Independent Spontaneously Forming Biomimetric Vesicles

    NASA Astrophysics Data System (ADS)

    Nieh, M.-P.; Harroun, T. A.; Raghunathan, V. A.; Glinka, C. J.; Katsaras, J.

    2003-10-01

    In this Letter we present small-angle neutron scattering data from a biomimetic system composed of the phospholipids dimyristoyl and dihexanoyl phosphorylcholine (DMPC and DHPC, respectively). Doping DMPC-DHPC multilamellar vesicles with either the negatively charged lipid dimyristoyl phosphorylglycerol (DMPG, net charge -1) or the divalent cation, calcium (Ca2+), leads to the spontaneous formation of energetically stabilized monodisperse unilamellar vesicles whose radii are concentration independent and in contrast with previous experimental observations.

  4. Small gas turbine engine technology

    NASA Technical Reports Server (NTRS)

    Niedzwiecki, Richard W.; Meitner, Peter L.

    1988-01-01

    Performance of small gas turbine engines in the 250 to 1,000 horsepower size range is significantly lower than that of large engines. Engines of this size are typically used in rotorcraft, commutercraft, general aviation, and cruise missile applications. Principal reasons for the lower efficiencies of a smaller engine are well known: component efficients are lower by as much as 8 to 10 percentage points because of size effects. Small engines are designed for lower cycle pressures and temperatures because of smaller blading and cooling limitations. The highly developed analytical and manufacturing techniques evolved for large engines are not directly transferrable to small engines. Thus, it was recognized that a focused effort addressing technologies for small engies was needed and could significantly impact their performance. Recently, in-house and contract studies were undertaken at the NASA Lewis Research Center to identify advanced engine cycle and component requirements for substantial performance improvement of small gas turbines for projected year 2000 applications. The results of both in-house research and contract studies are presented. In summary, projected fuel savings of 22 to 42 percent could be obtained. Accompanying direct operating cost reductions of 11 to 17 percent, depending on fuel cost, were also estimated. High payoff technologies are identified for all engine applications, and recent results of experimental research to evolve the high payoff technologies are described.

  5. Small rocket flowfield diagnostic chambers

    NASA Technical Reports Server (NTRS)

    Morren, Sybil; Reed, Brian

    1993-01-01

    Instrumented and optically-accessible rocket chambers are being developed to be used for diagnostics of small rocket (less than 440 N thrust level) flowfields. These chambers are being tested to gather local fluid dynamic and thermodynamic flowfield data over a range of test conditions. This flowfield database is being used to better understand mixing and heat transfer phenomena in small rockets, influence the numerical modeling of small rocket flowfields, and characterize small rocket components. The diagnostic chamber designs include: a chamber design for gathering wall temperature profiles to be used as boundary conditions in a finite element heat flux model; a chamber design for gathering inner wall temperature and static pressure profiles; and optically-accessible chamber designs, to be used with a suite of laser-based diagnostics for gathering local species concentration, temperature, density, and velocity profiles. These chambers were run with gaseous hydrogen/gaseous oxygen (GH2/GO2) propellants, while subsequent versions will be run on liquid oxygen/hydrocarbon (LOX/HC) propellants. The purpose, design, and initial test results of these small rocket flowfield diagnostic chambers are summarized.

  6. Cholesterol Independent Suppression of Lymphocyte Activation, Autoimmunity and Glomerulonephritis by Apolipoprotein A-I in Normocholesterolemic Lupus-Prone Mice

    PubMed Central

    Black, Leland L.; Srivastava, Roshni; Schoeb, Trenton R.; Moore, Ray D.; Barnes, Stephen; Kabarowski, Janusz H.

    2015-01-01

    Apolipoprotein A-I (ApoA-I), the major lipid-binding protein of high-density lipoprotein (HDL), can prevent autoimmunity and suppress inflammation in hypercholesterolemic mice by attenuating lymphocyte cholesterol accumulation and removing tissue oxidized lipids. However, whether ApoA-I mediates immune suppressive or anti-inflammatory effects in normocholesterolemic conditions and the mechanisms involved remain unresolved. We transferred bone marrow from SLE-prone Sle123 mice into normal, ApoA-I knockout (ApoA-I−/−) and ApoA-I transgenic (ApoA-Itg) mice. Increased ApoA-I in ApoA-Itg mice suppressed CD4+ T and B cell activation without changing lymphocyte cholesterol levels or reducing major ApoA-I-binding oxidized fatty acids. Unexpectedly, oxidized fatty acid peroxisome proliferator-activated receptor gamma (PPARγ) ligands 13-hydroxyoctadecadienoic acid (HODE) and 9-HODE were increased in lymphocytes of autoimmune ApoA-Itg mice. ApoA-I reduced Th1 cells independently of changes in CD4+FoxP3+ regulatory T cells or CD11c+ dendritic cell activation and migration. Follicular helper T cells, germinal center B cells and autoantibodies were also lower in ApoA-Itg mice. Transgenic ApoA-I also improved SLE-mediated glomerulonephritis. However, ApoA-I deficiency did not have opposite effects on autoimmunity or glomerulonephritis, possibly due to compensatory increases of ApoE on HDL. We conclude that although compensatory mechanisms prevent pro-inflammatory effects of ApoA-I deficiency in normocholesterolemic mice, increasing ApoA-I can attenuate lymphocyte activation and autoimmunity in SLE independently of cholesterol transport, possibly through oxidized fatty acid PPARγ ligands, and can reduce renal inflammation in glomerulonephritis. PMID:26466956

  7. A mass spectrometric determination of the conformation of dimeric apolipoprotein A-I in discoidal high density lipoproteins.

    PubMed

    Silva, R A Gangani D; Hilliard, George M; Li, Ling; Segrest, Jere P; Davidson, W Sean

    2005-06-21

    Discoidal forms of high density lipoproteins (HDL) are critical intermediates between lipid-poor apolipoprotein A-I (apo A-I), the major protein constituent of HDL, and the mature spherical forms that comprise the bulk of circulating particles. Thus, many studies have focused on understanding apoA-I structure in discs reconstituted in vitro. Recent theoretical and experimental work supports a "belt" model for apoA-I in which repeating amphipathic helical domains run parallel to the plane of the lipid disc. However, disc-associated apoA-I can adopt several tertiary arrangements that are consistent with a belt orientation. To distinguish among these, we cross-linked near-neighbor Lys groups in homogeneous 96 A discs containing exactly two molecules of apoA-I. After delipidation and tryptic digestion, mass spectrometry was used to identify 9 intermolecular and 11 intramolecular cross-links. The cross-linking pattern strongly suggests a "double-belt" molecular arrangement for apoA-I in which two apoA-I molecules wrap around the lipid bilayer disc forming two stacked rings in an antiparallel orientation with helix 5 of each apoA-I in juxtaposition (LL5/5 orientation). The data also suggests the presence of an additional double-belt orientation with a shifted helical registry (LL5/2 orientation). Furthermore, a 78 A particle with two molecules of apoA-I fit a similar double-belt motif with evidence for conformational changes in the N-terminus and the region near helix 5. A comparison of this work to a previous study is suggestive that a third molecule of apoA-I can form a hairpin in larger particles containing three molecules of apoA-I.

  8. Intravenously injected human apolipoprotein A-I rapidly enters the central nervous system via the choroid plexus.

    PubMed

    Stukas, Sophie; Robert, Jerome; Lee, Michael; Kulic, Iva; Carr, Michael; Tourigny, Katherine; Fan, Jianjia; Namjoshi, Dhananjay; Lemke, Kalistyne; DeValle, Nicole; Chan, Jeniffer; Wilson, Tammy; Wilkinson, Anna; Chapanian, Rafi; Kizhakkedathu, Jayachandran N; Cirrito, John R; Oda, Michael N; Wellington, Cheryl L

    2014-11-12

    Brain lipoprotein metabolism is dependent on lipoprotein particles that resemble plasma high-density lipoproteins but that contain apolipoprotein (apo) E rather than apoA-I as their primary protein component. Astrocytes and microglia secrete apoE but not apoA-I; however, apoA-I is detectable in both cerebrospinal fluid and brain tissue lysates. The route by which plasma apoA-I enters the central nervous system is unknown. Steady-state levels of murine apoA-I in cerebrospinal fluid and interstitial fluid are 0.664 and 0.120 μg/mL, respectively, whereas brain tissue apoA-I is ≈10% to 15% of its levels in liver. Recombinant, fluorescently tagged human apoA-I injected intravenously into mice localizes to the choroid plexus within 30 minutes and accumulates in a saturable, dose-dependent manner in the brain. Recombinant, fluorescently tagged human apoA-I accumulates in the brain for 2 hours, after which it is eliminated with a half-life of 10.3 hours. In vitro, human apoA-I is specifically bound, internalized, and transported across confluent monolayers of primary human choroid plexus epithelial cells and brain microvascular endothelial cells. Following intravenous injection, recombinant human apoA-I rapidly localizes predominantly to the choroid plexus. Because apoA-I mRNA is undetectable in murine brain, our results suggest that plasma apoA-I, which is secreted from the liver and intestine, gains access to the central nervous system primarily by crossing the blood-cerebrospinal fluid barrier via specific cellular mediated transport, although transport across the blood-brain barrier may also contribute to a lesser extent. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  9. Industry Research and Recommendations for Small Buildings and Small Portfolios

    SciTech Connect

    Langner, Rois; Hendron, Bob; Pless, Shanti; Huppert, Mark; Cochrane, Ric

    2013-12-01

    Small buildings have been left behind in the energy efficiency marketplace because financial and technical resources have flowed to larger commercial buildings. DOE's Building Technologies Office works with the commercial building industry to accelerate the uptake of energy efficiency technologies and techniques in existing and new commercial buildings (DOE 2013). BTO recognizes the SBSP sector'spotential for significant energy savings and the need for investments in resources that are tailored to this sector's unique needs. The industry research and recommendations described in this report identify potential approaches and strategic priorities that BTO could explore over the next 3-5 years that will support the implementation of high-potential energy efficiency opportunities for thisimportant sector. DOE is uniquely positioned to provide national leadership, objective information, and innovative tools, technologies, and services to support cost-effective energy savings in the fragmented and complex SBSP sector. Properly deployed, the DOE effort could enhance and complement current energy efficiency approaches. Small portfolios are loosely and qualitatively defined asportfolios of buildings that include only a small number of small buildings. This distinction is important because the report targets portfolio owners and managers who generally do not have staff and other resources to track energy use and pursue energy efficiency solutions.

  10. Energy Conservation in Small Schools. Small Schools Digest.

    ERIC Educational Resources Information Center

    Gardener, Clark

    Information concerning methods and available materials for conserving energy is needed by small, rural schools to offset continued increasing energy costs and lack of financial support and technical assistance. The first step in developing an energy conservation policy is to obtain school board commitment and to establish an energy saving policy.…

  11. Marketing the Uniqueness of Small Towns. Small Town Strategy.

    ERIC Educational Resources Information Center

    Hogg, David H.; Dunn, Douglas

    A small town can strengthen its local economy as a result of business people and concerned citizens collectively identifying that community's uniqueness and then capitalizing on it via advertising, personal selling, sales promotion, or publicity. This publication relates the science of marketing to communities. Seven simple techniques are provided…

  12. Health Promotion in Small Business

    PubMed Central

    McCoy, Kira; Stinson, Kaylan; Scott, Kenneth; Tenney, Liliana; Newman, Lee S.

    2015-01-01

    Objective To assess the evidence regarding the adoption and efficacy of worksite health promotion programs (WHPPs) in small businesses. Methods Peer-reviewed research articles were identified from a database search. Included articles were published before July 2013, described a study that used an experimental or quasiexperimental design and either assessed adoption of WHPPs or conducted interventions in businesses with fewer than 500 employees. A review team scored the study’s rigor using the WHO-adapted GRADEprofiler “quality of evidence” criteria. Results Of the 84 retrieved articles, 19 met study inclusion criteria. Of these, only two met criteria for high rigor. Conclusions Fewer small businesses adopt WHPPs compared with large businesses. Two high-rigor studies found that employees were healthier postintervention. Higher quality research is needed to better understand why small businesses rarely adopt wellness programs and to demonstrate the value of such programs. PMID:24905421

  13. Small Molecule CXCR3 Antagonists.

    PubMed

    Andrews, Stephen P; Cox, Rhona J

    2016-04-14

    Chemokines and their receptors are known to play important roles in disease. More than 40 chemokine ligands and 20 chemokine receptors have been identified, but, to date, only two small molecule chemokine receptor antagonists have been approved by the FDA. The chemokine receptor CXCR3 was identified in 1996, and nearly 20 years later, new areas of CXCR3 disease biology continue to emerge. Several classes of small molecule CXCR3 antagonists have been developed, and two have shown efficacy in preclinical models of inflammatory disease. However, only one CXCR3 antagonist has been evaluated in clinical trials, and there remain many opportunities to further investigate known classes of CXCR3 antagonists and to identify new chemotypes. This Perspective reviews the known CXCR3 antagonists and considers future opportunities for the development of small molecules for clinical evaluation.

  14. Effect of body mass index on apolipoprotein A-I kinetics in middle-aged men and postmenopausal women.

    PubMed

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

    2007-07-01

    The effect of body mass index (BMI) and obesity on apolipoprotein (apo) A-I levels and kinetics was examined by gender. Apo A-I kinetics were determined with a primed, constant infusion of deuterated leucine in the fed state in 19 men and 13 postmenopausal women. Compared with nonobese men, nonobese women had a higher level of high-density lipoprotein cholesterol (HDL-C) and apo A-I due to a 48% higher apo A-I production rate (PR) (P = .05). Obesity had no significant effects on apo A-I kinetics in women. In contrast, compared with nonobese men, obese men had a 9% lower apo A-I level due to a 64% higher fractional catabolic rate (FCR) partially offset by a 47% higher PR. Obese women had a 52% higher HDL-C than obese men (50 vs 33 mg/dL, respectively; P = .012), a finding related to the faster apo A-I FCR in obese men. BMI was directly correlated with apo A-I FCR (r = 0.84, P < .001) and PR (r = 0.79, P < .001) in men but not in women. Sixty-two percent of the variability in PR and 71% of the variability in FCR were due to BMI in men and only 3% and 23%, respectively, in women. In conclusion, BMI has a significant effect on apo A-I PR and FCR in men but not in women.

  15. Definition of human apolipoprotein A-I epitopes recognized by autoantibodies present in patients with cardiovascular diseases.

    PubMed

    Teixeira, Priscila Camillo; Ducret, Axel; Ferber, Philippe; Gaertner, Hubert; Hartley, Oliver; Pagano, Sabrina; Butterfield, Michelle; Langen, Hanno; Vuilleumier, Nicolas; Cutler, Paul

    2014-10-10

    Autoantibodies to apolipoprotein A-I (anti-apoA-I IgG) have been shown to be both markers and mediators of cardiovascular disease, promoting atherogenesis and unstable atherosclerotic plaque. Previous studies have shown that high levels of anti-apoA-I IgGs are independently associated with major adverse cardiovascular events in patients with myocardial infarction. Autoantibody responses to apoA-I can be polyclonal and it is likely that more than one epitope may exist. To identify the specific immunoreactive peptides in apoA-I, we have developed a set of methodologies and procedures to isolate, purify, and identify novel apoA-I endogenous epitopes. First, we generated high purity apoA-I from human plasma, using thiophilic interaction chromatography followed by enzymatic digestion specifically at lysine or arginine residues. Immunoreactivity to the different peptides generated was tested by ELISA using serum obtained from patients with acute myocardial infarction and high titers of autoantibodies to native apoA-I. The immunoreactive peptides were further sequenced by mass spectrometry. Our approach successfully identified two novel immunoreactive peptides, recognized by autoantibodies from patients suffering from myocardial infarction, who contain a high titer of anti-apoA-I IgG. The discovery of these epitopes may open innovative prognostic and therapeutic opportunities potentially suitable to improve current cardiovascular risk stratification.

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

    PubMed

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

    2011-11-01

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

  17. Purchasing cooperatives for small employers.

    PubMed

    Mallozzi, J

    1997-12-01

    Despite a booming economy, the number of uninsured Americans is rising. It hit nearly 42 million in 1996. Many of the uninsured work at businesses with fewer than 50 employees. Because small firms have traditionally found it difficult to provide health benefits, purchasing cooperatives have grown in scope and size across the country in recent years. By bringing small businesses together to buy insurance as a group, these organizations can help employers provide greater choice to their workers at a lower cost. However, to operate well in the insurance market, purchasing cooperatives must be well-designed and provided with adequate legal protections.

  18. Ectoparasites in small exotic mammals.

    PubMed

    Fehr, Michael; Koestlinger, Saskia

    2013-09-01

    Ectoparasites inhabiting the skin are responsible for significant problems in small mammals, owing to ingestion of blood, lymph, sebaceous secretions, and scavenging skin debris, as well as a hypersensitivity reaction to parasite antigen resulting in severe pruritus and subsequent self-trauma-induced lesions. In general practice, the most common diagnosis in exotic pets is an unspecified mite infestation, but other ectoparasites such as lice, fleas, insects, or even helminths may cause dermatologic diseases. If treatment with topical insecticides is planned, the small mammal should be isolated for a few hours to enable drying and spreading of the product.

  19. Orbit Mechanics about Small Asteroids

    NASA Technical Reports Server (NTRS)

    Scheeres, D. J.

    2007-01-01

    Space missions to small solar system bodies must deal with multiple perturbations acting on the spacecraft. These include strong perturbations from the gravity field and solar tide, but for small bodies the most important perturbations may arise from solar radiation pressure (SRP) acting on the spacecraft. Previous research has generally investigated the effect of the gravity field, solar tide, and SRP acting on a spacecraft trajectory about an asteroid in isolation and has not considered their joint effect. In this paper a more general theoretical discussion of the joint effects of these forces is given.

  20. Compilation of small RNA sequences.

    PubMed

    Shumyatsky, G; Reddy, R

    1992-05-11

    This is an update containing small RNA sequences published during 1991. Approximately two hundred small RNA sequences are available in this and earlier compilations. The hard copy print out of this set will be available directly from us (inquiries should be addressed to R. Reddy). These files are also available on GenBank computer. Sequences from various sources covered in earlier compilations (see Reddy, R. Nucl. Acids Res. 16:r71; Reddy, R. and Gupta, S. Nucl Acids Res. 1990 Supplement, 18:2231 and 1991 Supplement, 19:2073) are not included in this update but are listed below.

  1. Mycoplasma infections in small ruminants.

    PubMed

    Ruffin, D C

    2001-07-01

    Mycoplasmas have complex mechanisms of antigenic variation that allow them to evade the immune system. These organisms cause a variety of clinical syndromes that can have a significant economic effect on small ruminant production. The syndromes range from acute septicemia and death to chronic infection resulting in decreased production. Recent research findings have shed light on the means by which these organisms evade the host immune response and cause or contribute to the development of disease in the host. This article provides a review of the pathogenesis, clinical signs, and treatment options for common disease syndromes involving Mycoplasma spp. in small ruminants.

  2. Small intestinal physiology and pathophysiology.

    PubMed

    Sarna, S K; Otterson, M F

    1989-06-01

    The small intestine, like the rest of the gastrointestinal tract, is an intelligent organ. It generates a wide variety of motor patterns to meet motility requirements in different situations. Its basic motor function after a meal is to mix the chyme with exocrine and intestinal secretions, agitate its contents to uniformly and evenly expose them to the mucosal surface, and to propel them distally at a rate that allows optimal absorption of food components, and reabsorption of bile. Most of these functions are performed by individual phasic contractions. In humans, the phasic contractions are largely disorganized in time and space. These contractions may cause mixing and agitation of luminal contents with slow distal propulsion. Occasionally, an individual contraction of large amplitude and long duration migrates over several centimeters and may rapidly propel the contents over this distance. In general, the spatial and temporal relationships of individual phasic contractions become less organized distally, resulting in a slower propulsion rate in the distal small intestine than in the proximal small intestine. The migrating clustered contractions generated after a meal may also be propulsive, but because of their unpredictable and irregular occurrence, their precise role in postprandial propulsion is incompletely understood. Rapidly migrating contractions may occur when the electrical control activity is obliterated by pharmacologic agents or during parasitic infections. Their effects on motility are not known yet. Between meals, when digestion is complete, the small intestine generates migrating motor complexes that help keep the small intestine clean by dislodging debris from the villi and dumping them into the colon. This may prevent decay of these materials in the small intestine and limit their contribution to bacterial overgrowth. Giant migrating contractions may perform a similar function in the distal small intestine as well as return any refluxed fecal

  3. Apolipoprotein A-I and Paraoxonase-1 Are Potential Blood Biomarkers for Ischemic Stroke Diagnosis.

    PubMed

    Walsh, Kyle B; Hart, Kimberly; Roll, Susan; Sperling, Matthew; Unruh, Dusten; Davidson, W Sean; Lindsell, Christopher J; Adeoye, Opeolu

    2016-06-01

    Blood biomarkers for ischemic and hemorrhagic stroke diagnosis remain elusive. Recent investigations suggested that apolipoprotein (Apo), matrix metalloproteinase (MMP), and paraoxonase-1 may be associated with stroke. We hypothesized that Apo A-I, Apo C-I, Apo C-III, MMP-3, MMP-9, and paraoxonase-1 are differentially expressed in ischemic stroke, hemorrhagic stroke, and controls. In a single-center prospective observational study, consecutive stroke cases were enrolled if blood samples were obtainable within 12 hours of symptom onset. Age- (±5 years), race-, and sex-matched controls were recruited. Multiplex assays were used to measure protein levels. The Wilcoxon signed-rank test and the Mann-Whitney U-test were used to compare biomarker values between ischemic stroke patients and controls, hemorrhagic stroke patients and controls, and ischemic and hemorrhagic stroke patients. The 95% confidence intervals (CIs) for the difference of 2 medians were calculated. Fourteen ischemic stroke case-control pairs and 23 intracerebral hemorrhage (ICH) case-control pairs were enrolled. Median Apo A-I levels were lower in ischemic stroke cases versus controls (140 mg/dL versus 175 mg/dL, difference of 35 mg/dL, 95% CI -54 to -16) and in ischemic stroke versus ICH cases (140 mg/dL versus 180 mg/dL, difference of 40 mg/dL, 95% CI -57 to -23). Median paraoxonase-1 was lower in ischemic stroke cases than in both ICH cases and matched controls. Median Apo C-I was slightly lower in ischemic stroke cases than in ICH cases. There were no differences between groups for MMP-3, MMP-9, and Apo C-III. Apo A-I and paraoxonase-1 levels may be clinically useful for ischemic stroke diagnosis and for differentiating between ischemic and hemorrhagic strokes. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  4. Francisella tularensis Subtype A.II Genomic Plasticity in Comparison with Subtype A.I

    PubMed Central

    Larson, Marilynn A.; Nalbantoglu, Ufuk; Sayood, Khalid; Zentz, Emily B.; Bartling, Amanda M.; Francesconi, Stephen C.; Fey, Paul D.; Dempsey, Michael P.; Hinrichs, Steven H.

    2015-01-01

    Although Francisella tularensis is considered a monomorphic intracellular pathogen, molecular genotyping and virulence studies have demonstrated important differences within the tularensis subspecies (type A). To evaluate genetic variation within type A strains, sequencing and assembly of a new subtype A.II genome was achieved for comparison to other completed F. tularensis type A genomes. In contrast with the F. tularensis A.I strains (SCHU S4, FSC198, NE061598, and TI0902), substantial genomic variation was observed between the newly sequenced F. tularensis A.II strain (WY-00W4114) and the only other publically available A.II strain (WY96-3418). Genome differences between WY-00W4114 and WY96-3418 included three major chromosomal translocations, 1580 indels, and 286 nucleotide substitutions of which 159 were observed in predicted open reading frames and 127 were located in intergenic regions. The majority of WY-00W4114 nucleotide deletions occurred in intergenic regions, whereas most of the insertions and substitutions occurred in predicted genes. Of the nucleotide substitutions, 48 (30%) were synonymous and 111 (70%) were nonsynonymous. WY-00W4114 and WY96-3418 nucleotide polymorphisms were predominantly G/C to A/T allelic mutations, with WY-00W4114 having more A+T enrichment. In addition, the A.II genomes contained a considerably higher number of intact genes and longer repetitive sequences, including transposon remnants than the A.I genomes. Together these findings support the premise that F. tularensis A.II may have a fitness advantage compared to the A.I subtype due to the higher abundance of functional genes and repeated chromosomal sequences. A better understanding of the selective forces driving F. tularensis genetic diversity and plasticity is needed. PMID:25918839

  5. [Screening and identification of apolipoprotein A-I as a potential marker for hepatoblastoma in children].

    PubMed

    Guo, Li-Hua; Zhao, Wei; Zhang, Jun-Jie; Zhang, Qian; Fan, Ying-Zhong; Wang, Jia-Xiang

    2016-12-01

    To screen and identify serum biomarkers for childhood hepatoblastoma (HB). The serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins. After SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group. Apo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.

  6. Apolipoprotein A-I mimetic peptide treatment inhibits inflammatory responses and improves survival in septic rats

    PubMed Central

    Zhang, Zhenghao; Datta, Geeta; Zhang, Yun; Miller, Andrew P.; Mochon, Paulina; Chen, Yiu-Fai; Chatham, John; Anantharamaiah, G. M.; White, C. Roger

    2009-01-01

    Systemic inflammation induces a multiple organ dysfunction syndrome that contributes to morbidity and mortality in septic patients. Since increasing plasma apolipoprotein A-I (apoA-I) and HDL may reduce the complications of sepsis, we tested the hypothesis that the apoA-I mimetic peptide 4F confers similar protective effects in rats undergoing cecal ligation and puncture (CLP) injury. Male Sprague-Dawley rats were randomized to undergo CLP or sham surgery. IL-6 levels were significantly elevated in plasma by 6 h after CLP surgery compared with shams. In subsequent studies, CLP rats were further subdivided to receive vehicle or 4F (10 mg/kg) by intraperitoneal injection, 6 h after sepsis induction. Sham-operated rats received saline. Echocardiographic studies showed a reduction in left ventricular end-diastolic volume, stroke volume, and cardiac output (CO) 24 h after CLP surgery. These changes were associated with reduced blood volume and left ventricular filling pressure. 4F treatment improved blood volume status, increased CO, and reduced plasma IL-6 in CLP rats. Total cholesterol (TC) and HDL were 79 ± 5 and 61 ± 4 mg/dl, respectively, in sham rats. TC was significantly reduced in CLP rats (54 ± 3 mg/dl) due to a reduction in HDL (26 ± 3 mg/dl). 4F administration to CLP rats attenuated the reduction in TC (69 ± 4 mg/dl) and HDL (41 ± 3 mg/dl) and prevented sepsis-induced changes in HDL protein composition. Increased plasma HDL in 4F-treated CLP rats was associated with an improvement in CO and reduced mortality. It is proposed that protective effects of 4F are related to its ability to prevent the sepsis-induced reduction in plasma HDL. PMID:19561306

  7. Dietary fat elevates hepatic apoA-I production by increasing the fraction of apolipoprotein A-I mRNA in the translating pool.

    PubMed

    Azrolan, N; Odaka, H; Breslow, J L; Fisher, E A

    1995-08-25

    Elevated plasma high density lipoprotein cholesterol (HDL-C) levels are associated with a decreased risk for coronary heart disease. Ironically, diets enriched in saturated fat and cholesterol (HF/HC diets), which tend to accelerate atherosclerotic processes by increasing LDL cholesterol levels, also raise HDL-C. We have recently reported, using a human apoA-I (hapoA-1) transgenic mouse model, that the elevation of HDL-C by a HF/HC diet is attributable, in part, to an increase in the hepatic production of hapoA-1. To further define the hepatocellular processes associated with this induction, we have prepared primary hepatocytes from hapoA-1 transgenic mice. Rates of hapoA-1 secretion were 40% greater from cells prepared from animals fed the HF/HC relative to a low fat-low cholesterol (LF/LC) control diet. The abundance of hapoA-1 mRNA in these cells was similar between hepatocytes prepared from the HF/HC and LF/LC diet fed animals, suggesting a post-transcriptional mechanism that does not involve mRNA stability. Inhibition of secretion using brefeldin A revealed an increase in cellular hapoA-1 accumulation. Thus, the HF/HC diet apparently affects hepatic hapoA-1 production via a mechanism that is manifest prior to the exit of newly synthesized hapoA-1 from the Golgi. Pulse-chase experiments revealed a 39% greater peak hapoA-1 synthesis, with no difference in the degradation of total labeled hapoA-1 protein, as a result of the HF/HC diet feeding. Finally, resolution of liver S10 extracts via sucrose density sedimentation and metrizamide density equilibrium gradient centrifugation analyses both revealed similar increases (31 and 24%, respectively) in the relative percentage of hapoA-1 mRNA associated with the translating polysomal fractions as a result of the HF/HC feeding. Together, these data suggest that the HF/HC diet affects hepatic hapoA-1 production via a specific modulation in the relative amount of hapoA-1 mRNA in the polysomal pool. These observations

  8. Department of the Navy Small Business Programs

    DTIC Science & Technology

    2014-08-13

    small business concerns and to women -owned small business concerns eligible under the Women -Owned Small Business Program. The dollar...2014 For All US-Based Women Owned Small Business Awards Over $ 200M Over $ 100M Over...Department of the Navy Small Business Programs Gold Coast August 13, 2014 Report Documentation Page Form ApprovedOMB No. 0704-0188

  9. Serum apolipoproteins A-I and B in 2,854 children from a biracial community: Bogalusa Heart Study.

    PubMed

    Srinivasan, S R; Freedman, D S; Sharma, C; Webber, L S; Berenson, G S

    1986-08-01

    Serum apolipoprotein A-I (apo A-I) and apolipoprotein B (apo B) profiles were examined in 2,854 children, 5 to 17 years of age, from a total biracial community. Black boys had higher apo A-I levels than white boys (P less than .001), whereas girls showed no such race-related difference. Black-white difference in apo A-I persisted among boys with similar triglyceride levels provided that triglyceride levels were high. The ratio of high-density lipoprotein cholesterol (HDL-C)/apo A-I was higher in black than in white children, irrespective of sex (P less than .001). Only black children showed sex-related differences for apo A-I (boys greater than girls, P less than .05). Sex-related differences were seen in white children for HDL-C/apo A-I ratio (boys greater than girls, P less than .001) and in children of both races for apoB (girls greater than boys, P less than .01). Age-related changes were more apparent for apo A-I and HDL-C/apo A-I ratio than for apo B. A progressive decrease in apo A-I was noted during sexual maturation only in white boys. The magnitude of inverse association of apo B to HDL-C was less strong in black children (P less than .01). Although apo A-I was inversely correlated with very low-density lipoprotein cholesterol and triglycerides in white children, no association was noted in black children. These findings are indicative of intrinsic metabolic differences among the race-sex groups, resulting in variability in lipoprotein composition and levels and atherogenic potential.

  10. Biological productivity in small impoundments

    USDA-ARS?s Scientific Manuscript database

    Most ponds and small impoundments are built or used with a principal use in mind. That use may be recreational fishing, commercial aquaculture, waterfowl hunting, potable water storage, irrigation water supply, livestock watering, stormwater retention, landscaping, swimming, or others. In practice, ...

  11. ADA Guide for Small Businesses.

    ERIC Educational Resources Information Center

    Department of Justice, Washington, DC. Civil Rights Div.

    This guide presents an informal overview of some basic Americans with Disabilities Act (ADA) requirements for small businesses that provide goods or services to the public. References to key sections of the regulations or other information are included. The first section describes the ADA briefly. Section two lists the 12 categories of public…

  12. Reimagining Education in Small Towns

    ERIC Educational Resources Information Center

    Carr, Patrick J.; Kefalas, Maria J.

    2010-01-01

    Things are not going so well in small-town America. While the so-called "Great Recession" of the moment has focused considerable attention on the travails of Main Street and Middle America, the truth is that the troubles that plague such places have been a long time in the making. For the past 30 years, nonmetropolitan counties and the…

  13. Small Secondary Schools Administrative Manual.

    ERIC Educational Resources Information Center

    Alaska State Dept. of Education, Juneau. Office of Public Information and Publications.

    A guideline for providing quality secondary education in situations where only a relatively small number of students are involved, this manual describes the organizational options for high school programs. The options discussed are regional high schools, area secondary schools, and local high schools. Local high schools can be further classified…

  14. Netbooks: Small but Powerful Friends

    ERIC Educational Resources Information Center

    Descy, Don E.

    2009-01-01

    Netbooks, sometimes called "mini-notebooks," are lightweight, small, and low-priced computers. Some writers ridicule them by calling them "one of the hottest tech toys of the year" (Saltzman, 2008). Others enthusiastically embrace them as "my perfect new travel companion" (Grossman, 2009). Netbooks are not toys. They are honest-to-goodness real…

  15. Small Business Incubator Resource Kit.

    ERIC Educational Resources Information Center

    Small Business Administration, Washington, DC.

    This kit consists of a set of resources to assist those interested in the start-up and management (incubation) of a new business. A guide to starting and managing a small business incubator (SBI) is provided. Included in the guide are the following: a discussion of the role and characteristics of the SBI concept; guidelines for carrying out the…

  16. School Size: Is Small Better?

    ERIC Educational Resources Information Center

    Lashway, Larry

    1999-01-01

    This bulletin contains synopses of five works that consider the issue of school size from a variety of viewpoints. (1) "School Size' School Climate, and School Performance" (Kathleen Cotton) reviews the research evidence on school size, finding strong support for the advantages of small schools. (2) "Is Bigger Really Better?" (Kenneth Stevenson…

  17. Final Barrier: Small System Compliance

    EPA Science Inventory

    This presentation will discuss the use of point-of-use (POU) technology for small drinking water systems. Information will be provided on the USEPA regulations that allow the use of POU for compliance and the technologies that are listed as SSCT for radium and arsenic. Listing o...

  18. Small Mammals, Reptiles, and Amphibians

    Treesearch

    Bryce Rickel

    2005-01-01

    This chapter focuses on small mammals, reptiles, and amphibians that inhabit the grasslands within the Southwestern Region of the USDA Forest Service. The chapter is not intended to be an all inclusive list of species, but rather to address the species that play important roles in grassland ecosystems and that often are associated with the management of grasslands....

  19. Big Opportunities in Small Science

    ERIC Educational Resources Information Center

    Dewey, T. Gregory

    2007-01-01

    A transformation is occurring that will have a major impact on how academic science is done and how scientists are trained. That transformation--driven by declining federal funds, as well as by the rising cost of technology and the need for costly, labor-intensive interdisciplinary approaches--is from small science to big science. It is…

  20. Modeling Interactions in Small Groups

    ERIC Educational Resources Information Center

    Heise, David R.

    2013-01-01

    A new theory of interaction within small groups posits that group members initiate actions when tension mounts between the affective meanings of their situational identities and impressions produced by recent events. Actors choose partners and behaviors so as to reduce the tensions. A computer model based on this theory, incorporating reciprocal…