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Sample records for acid transport systems

  1. Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters.

    PubMed

    Babu, Ellappan; Kanai, Yoshikatsu; Chairoungdua, Arthit; Kim, Do Kyung; Iribe, Yuji; Tangtrongsup, Sahatchai; Jutabha, Promsuk; Li, Yuewei; Ahmed, Nesar; Sakamoto, Shinichi; Anzai, Naohiko; Nagamori, Seishi; Endou, Hitoshi

    2003-10-31

    A cDNA that encodes a novel Na+-independent neutral amino acid transporter was isolated from FLC4 human hepatocarcinoma cells by expression cloning. When expressed in Xenopus oocytes, the encoded protein designated LAT3 (L-type amino acid transporter 3) transported neutral amino acids such as l-leucine, l-isoleucine, l-valine, and l-phenylalanine. The LAT3-mediated transport was Na+-independent and inhibited by 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid, consistent with the properties of system L. Distinct from already known system L transporters LAT1 and LAT2, which form heterodimeric complex with 4F2 heavy chain, LAT3 was functional by itself in Xenopus oocytes. The deduced amino acid sequence of LAT3 was identical to the gene product of POV1 reported as a prostate cancer-up-regulated gene whose function was not determined, whereas it did not exhibit significant similarity to already identified transporters. The Eadie-Hofstee plots of LAT3-mediated transport were curvilinear, whereas the low affinity component is predominant at physiological plasma amino acid concentration. In addition to amino acid substrates, LAT3 recognized amino acid alcohols. The transport of l-leucine was electroneutral and mediated by a facilitated diffusion. In contrast, l-leucinol, l-valinol, and l-phenylalaninol, which have a net positive charge induced inward currents under voltage clamp, suggesting these compounds are transported by LAT3. LAT3-mediated transport was inhibited by the pretreatment with N-ethylmaleimide, consistent with the property of system L2 originally characterized in hepatocyte primary culture. Based on the substrate selectivity, affinity, and N-ethylmaleimide sensitivity, LAT3 is proposed to be a transporter subserving system L2. LAT3 should denote a new family of organic solute transporters. PMID:12930836

  2. Characterization of a broad-scope amino acid transport system in sand dollars

    SciTech Connect

    Davis, J.P.; Bellis, S.; Stephens, G.C. )

    1988-03-01

    Both echinoderm embryos and adults take up {sup 14}C-labelled-{alpha}-amino acids by an apparent broad-scope transport system. This transporter can be characterized as follows: alanine transport is not blocked by {alpha}-(methylamino)isobutyric acid. Leucine and other lipophilic neutral amino acids are preferentially transported. Transport is sodium dependent and blocked by 2-aminobicyclo-(2,2,1)heptane-2-carboxyclic acid. Lysine and aspartate transport is inhibited by lipophilic neutral amino acids. Taurine, a {beta}-neutral amino acid is translocated via a second and independent carrier.

  3. Oleic acid stimulates system A amino acid transport in primary human trophoblast cells mediated by toll-like receptor 4.

    PubMed

    Lager, Susanne; Gaccioli, Francesca; Ramirez, Vanessa I; Jones, Helen N; Jansson, Thomas; Powell, Theresa L

    2013-03-01

    Obese women have an increased risk to deliver large babies. However, the mechanisms underlying fetal overgrowth in these pregnancies are not well understood. Obese pregnant women typically have elevated circulating lipid levels. We tested the hypothesis that fatty acids stimulate placental amino acid transport, mediated via toll-like receptor 4 (TLR4) and mammalian target of rapamycin (mTOR) signaling pathways. Circulating NEFA levels and placental TLR4 expression were assessed in women with varying prepregnancy body mass index (BMI). The effects of oleic acid on system A and system L amino acid transport, and on the activation of the mTOR (4EBP1, S6K1, rpS6), TLR4 (IĸB, JNK, p38 MAPK), and STAT3 signaling pathways were determined in cultured primary human trophoblast cells. Maternal circulating NEFAs (n = 33), but not placental TLR4 mRNA expression (n = 16), correlated positively with BMI (P < 0.05). Oleic acid increased trophoblast JNK and STAT3 phosphorylation (P < 0.05), whereas mTOR activity was unaffected. Furthermore, oleic acid doubled trophoblast system A activity (P < 0.05), without affecting system L activity. siRNA-mediated silencing of TLR4 expression prevented the stimulatory effect of oleic acid on system A activity. Our data suggest that maternal fatty acids can increase placental nutrient transport via TLR4, thereby potentially affecting fetal growth.

  4. Characterization of methylaminoisobutyric acid transport by system A in rat mammary gland.

    PubMed

    Tovar, A R; Avila, E; DeSantiago, S; Torres, N

    2000-07-01

    During lactation, the mammary gland has a large demand for amino acids for the synthesis of milk proteins and fatty acids. Arteriovenous differences in amino acids across the mammary gland show an elevated uptake of small neutral amino acids that are mainly transported via system A. The purpose of this study was to characterize the transport of methylaminoisobutyric acid (MeAIB), an amino acid analog used to model transport by system A in lactating rat mammary gland explants. MeAIB accumulation in mammary gland cells increased steadily, and after 3 hours of incubation, the intracellular concentration of the analog was 8-fold higher than the concentration in the medium. MeAIB transport into mammary gland explants showed a Km of 3.3 +/- 0.4 mmol/L and a maximal velocity (Vmax) of 555 +/- 23 pmol/microL intracellular fluid (ICF) x min, indicating a system with high capacity but low affinity for its substrate. MeAIB transport into mammary tissue depended highly on Na+, and the uptake was inhibited by addition of natural and analog small neutral amino acids. Cationic, anionic, and large neutral amino acids did not reduce MeAIB transport into mammary gland explants. Preincubation of mammary gland explants in an amino acid-free medium stimulated MeAIB transport, suggesting an adaptive regulation. The addition of an equimolar mixture of alanine, glycine, and serine to the preincubation medium inhibited stimulation of MeAIB transport. Furthermore, stimulation of MeAIB uptake by amino acid starvation was also prevented by the addition of actinomycin D, cycloheximide, tunicamycin, and colchicine. Dibutyryl cyclic adenosine monophosphate (cAMP) increased MeAIB uptake, whereas phorbol 12-myristate 13-acetate (PMA) did not stimulate MeAIB transport. During the first postweaning days, kinetic analyses showed a decrease of 27% in the Vmax. Injection of rat lactating mammary gland mRNA into Xenopus laevis oocytes induced expression of the MeAIB transport system; however, the

  5. Mutation and gene transfer of neutral amino acid transport System L genes in mammalian cells

    SciTech Connect

    El-Gewely, M.R.; Collarini, E.J.; Campbell, G.S.; Oxender, D.L.

    1987-05-01

    The authors are attempting to clone the genes coding for amino acid transport System L. Chinese hamster ovary (CHO) cell mutants that are temperature sensitive in their leucyl-tRNA synthetase show temperature-dependent regulation of System L. Temperature resistant mutants isolated from these cells have constitutively derepressed System L activity. Somatic cell fusion studies using these mutants have suggested that a trans-acting element controls regulation of System L. Mutants with reduced transport activity were isolated by a TH-suicide selection. The growth of these mutant cells is limited by the transport defect. CHO mutants were transformed with a human cosmid library, followed by selection at high temperatures and low leucine concentrations. Some transformants have increased levels of System L activity, suggesting that human genes coding for leucine transport have been incorporated into the CHO genome. Human sequences were rescued by a lambda in vitro packaging system. These sequences hybridize to vector and total human DNA. Experiments are being done to confirm that these sequences indeed code for transport System L. They are also attempting to label membrane components of amino acid transporters by group-specific modifying reagents.

  6. Genetic evidence of a high-affinity cyanuric acid transport system in Pseudomonas sp. ADP.

    PubMed

    Platero, Ana I; Santero, Eduardo; Govantes, Fernando

    2014-03-01

    The Pseudomonas sp. ADP plasmid pADP-1 encodes the activities involved in the hydrolytic degradation of the s-triazine herbicide atrazine. Here, we explore the presence of a specific transport system for the central intermediate of the atrazine utilization pathway, cyanuric acid, in Pseudomonas sp. ADP. Growth in fed-batch cultures containing limiting cyanuric acid concentrations is consistent with high-affinity transport of this substrate. Acquisition of the ability to grow at low cyanuric acid concentrations upon conjugal transfer of pADP1 to the nondegrading host Pseudomonas putida KT2442 suggests that all activities required for this phenotype are encoded in this plasmid. Co-expression of the pADP1-borne atzDEF and atzTUVW genes, encoding the cyanuric acid utilization pathway and the subunits of an ABC-type solute transport system, in P. putida KT2442 was sufficient to promote growth at cyanuric acid concentrations as low as 50 μM in batch culture. Taken together, our results strongly suggest that the atzTUVW gene products are involved in high-affinity transport of cyanuric acid.

  7. The contribution of SNAT1 to system A amino acid transporter activity in human placental trophoblast

    SciTech Connect

    Desforges, M.; Greenwood, S.L.; Glazier, J.D.; Westwood, M.; Sibley, C.P.

    2010-07-16

    Research highlights: {yields} mRNA levels for SNAT1 are higher than other system A subtype mRNAs in primary human cytotrophoblast. {yields} SNAT1 knockdown in cytotrophoblast cells significantly reduces system A activity. {yields} SNAT1 is a key contributor to system A-mediated amino acid transport in human placenta. -- Abstract: System A-mediated amino acid transport across the placenta is important for the supply of neutral amino acids needed for fetal growth. All three system A subtypes (SNAT1, 2, and 4) are expressed in human placental trophoblast suggesting there is an important biological role for each. Placental system A activity increases as pregnancy progresses, coinciding with increased fetal nutrient demands. We have previously shown SNAT4-mediated system A activity is higher in first trimester than at term, suggesting that SNAT1 and/or SNAT2 are responsible for the increased system A activity later in gestation. However, the relative contribution of each subtype to transporter activity in trophoblast at term has yet to be evaluated. The purpose of this study was to identify the predominant subtype of system A in cytotrophoblast cells isolated from term placenta, maintained in culture for 66 h, by: (1) measuring mRNA expression of the three subtypes and determining the Michaelis-Menten constants for uptake of the system A-specific substrate, {sup 14}C-MeAIB, (2) investigating the contribution of SNAT1 to total system A activity using siRNA. Results: mRNA expression was highest for the SNAT1 subtype of system A. Kinetic analysis of {sup 14}C-MeAIB uptake revealed two distinct transport systems; system 1: K{sub m} = 0.38 {+-} 0.12 mM, V{sub max} = 27.8 {+-} 9.0 pmol/mg protein/20 min, which resembles that reported for SNAT1 and SNAT2 in other cell types, and system 2: K{sub m} = 45.4 {+-} 25.0 mM, V{sub max} = 1190 {+-} 291 pmol/mg protein/20 min, which potentially represents SNAT4. Successful knockdown of SNAT1 mRNA using target-specific si

  8. Bile acid transporters

    PubMed Central

    Dawson, Paul A.; Lan, Tian; Rao, Anuradha

    2009-01-01

    In liver and intestine, transporters play a critical role in maintaining the enterohepatic circulation and bile acid homeostasis. Over the past two decades, there has been significant progress toward identifying the individual membrane transporters and unraveling their complex regulation. In the liver, bile acids are efficiently transported across the sinusoidal membrane by the Na+ taurocholate cotransporting polypeptide with assistance by members of the organic anion transporting polypeptide family. The bile acids are then secreted in an ATP-dependent fashion across the canalicular membrane by the bile salt export pump. Following their movement with bile into the lumen of the small intestine, bile acids are almost quantitatively reclaimed in the ileum by the apical sodium-dependent bile acid transporter. The bile acids are shuttled across the enterocyte to the basolateral membrane and effluxed into the portal circulation by the recently indentified heteromeric organic solute transporter, OSTα-OSTβ. In addition to the hepatocyte and enterocyte, subgroups of these bile acid transporters are expressed by the biliary, renal, and colonic epithelium where they contribute to maintaining bile acid homeostasis and play important cytoprotective roles. This article will review our current understanding of the physiological role and regulation of these important carriers. PMID:19498215

  9. Theory of ion transport with fast acid-base equilibrations in bioelectrochemical systems

    NASA Astrophysics Data System (ADS)

    Dykstra, J. E.; Biesheuvel, P. M.; Bruning, H.; Ter Heijne, A.

    2014-07-01

    Bioelectrochemical systems recover valuable components and energy in the form of hydrogen or electricity from aqueous organic streams. We derive a one-dimensional steady-state model for ion transport in a bioelectrochemical system, with the ions subject to diffusional and electrical forces. Since most of the ionic species can undergo acid-base reactions, ion transport is combined in our model with infinitely fast ion acid-base equilibrations. The model describes the current-induced ammonia evaporation and recovery at the cathode side of a bioelectrochemical system that runs on an organic stream containing ammonium ions. We identify that the rate of ammonia evaporation depends not only on the current but also on the flow rate of gas in the cathode chamber, the diffusion of ammonia from the cathode back into the anode chamber, through the ion exchange membrane placed in between, and the membrane charge density.

  10. Theory of ion transport with fast acid-base equilibrations in bioelectrochemical systems.

    PubMed

    Dykstra, J E; Biesheuvel, P M; Bruning, H; Ter Heijne, A

    2014-07-01

    Bioelectrochemical systems recover valuable components and energy in the form of hydrogen or electricity from aqueous organic streams. We derive a one-dimensional steady-state model for ion transport in a bioelectrochemical system, with the ions subject to diffusional and electrical forces. Since most of the ionic species can undergo acid-base reactions, ion transport is combined in our model with infinitely fast ion acid-base equilibrations. The model describes the current-induced ammonia evaporation and recovery at the cathode side of a bioelectrochemical system that runs on an organic stream containing ammonium ions. We identify that the rate of ammonia evaporation depends not only on the current but also on the flow rate of gas in the cathode chamber, the diffusion of ammonia from the cathode back into the anode chamber, through the ion exchange membrane placed in between, and the membrane charge density. PMID:25122405

  11. Conformationally-restricted amino acid analogues bearing a distal sulfonic acid show selective inhibition of system x(c)(-) over the vesicular glutamate transporter.

    PubMed

    Etoga, Jean-Louis G; Ahmed, S Kaleem; Patel, Sarjubhai; Bridges, Richard J; Thompson, Charles M

    2010-04-15

    A panel of amino acid analogs and conformationally-restricted amino acids bearing a sulfonic acid were synthesized and tested for their ability to preferentially inhibit the obligate cysteine-glutamate transporter system x(c)(-) versus the vesicular glutamate transporter (VGLUT). Several promising candidate molecules were identified: R/S-4-[4'-carboxyphenyl]-phenylglycine, a biphenyl substituted analog of 4-carboxyphenylglycine and 2-thiopheneglycine-5-sulfonic acid both of which reduced glutamate uptake at system x(c)(-) by 70-75% while having modest to no effect on glutamate uptake at VGLUT.

  12. Canine amino acid transport system Xc(-): cDNA sequence, distribution and cystine transport activity in lens epithelial cells.

    PubMed

    Maruo, Takuya; Kanemaki, Nobuyuki; Onda, Ken; Sato, Reiichiro; Ichihara, Nobuteru; Ochiai, Hideharu

    2014-04-01

    The cystine transport activity of a lens epithelial cell line originated from a canine mature cataract was investigated. The distinct cystine transport activity was observed, which was inhibited to 28% by extracellular 1 mM glutamate. The cDNA sequences of canine cysteine/glutamate exchanger (xCT) and 4F2hc were determined. The predicted amino acid sequences were 527 and 533 amino acid polypeptides, respectively. The amino acid sequences of canine xCT and 4F2hc showed high similarities (>80%) to those of humans. The expression of xCT in lens epithelial cell line was confirmed by western blot analysis. RT-PCR analysis revealed high level expression only in the brain, and it was below the detectable level in other tissues.

  13. Light-Activated Amino Acid Transport Systems in Halobacterium halobium Envelope Vesicles: Role of Chemical and Electrical Gradients

    NASA Technical Reports Server (NTRS)

    MacDonald, Russell E.; Greene, Richard V.; Lanyi, Janos K.

    1977-01-01

    The accumulation of 20 commonly occurring L-amino acids by cell envelope vesicles of Halobacterium halobium, in response to light-induced membrane potential and an artificially created sodium gradient, has been studied. Nineteen of these amino acids are actively accumulated under either or both of these conditions. Glutamate is unique in that its uptake is driven only by a chemical gradient for sodium. Amino acid concentrations at half-maximal uptake rates (Km) and maximal transport rates (V(sub max) have been determined for the uptake of all 19 amino acids. The transport systems have been partially characterized with respect to groups of amino acids transported by common carriers, cation effects, and relative response to the electrical and chemical components of the sodium gradient, the driving forces for uptake. The data presented clearly show that the carrier systems, which are responsible for uptake of individual amino acids, are as variable in their properties as those found in other organisms, i. e., some are highly specific for individual amino acids, some transport several amino acids competitively, some are activated by a chemical gradient of sodium only, and some function also in the complete absence of such a gradient. For all amino acids, Na(+) and K(+) are both required for maximal rate of uptake. The carriers for L-leucine and L-histidine are symmetrical in that these amino acids are transported in both directions across the vesicle membrane. It is suggested that coupling of substrate transport to metabolic energy via transient ionic gradients may be a general phenomenon in procaryotes.

  14. Threonine deprivation rapidly activates the system A amino acid transporter in primary cultures of rat neurons from the essential amino acid sensor in the anterior piriform cortex.

    PubMed

    Blais, Anne; Huneau, Jean-François; Magrum, Linda J; Koehnle, Thomas J; Sharp, James W; Tomé, Daniel; Gietzen, Dorothy W

    2003-07-01

    Omnivores show recognition of essential (indispensable) amino acid deficiency by changing their feeding behavior within 20 min, yet the cellular mechanisms of amino acid sensation in eukaryotes are poorly understood. The anterior piriform cortex (APC) of the brain in rats or its analog in birds likely houses the in vivo amino acid chemosensor. Because amino acid transporters adapt rapidly to essential amino acid deficiency in several cell models, we hypothesized that activation of electrogenic amino acid transport in APC neurons might contribute to the function of the amino acid sensor. We evaluated transport systems in primary cultures of neurons from the APC, hippocampus and cerebellum, or glia, incubated in complete or threonine-devoid (deficient) medium. After 10 min in deficient medium, uptake of threonine or a system A-selective substrate, methyl amino-isobutyric acid, was increased 60% in APC neurons only (P < 0.05). These results demonstrated upregulation of system A, an electrogenic amino acid-sodium symporter. This depletion-induced activation required sodium, intact intracellular trafficking, and phosphorylation of signal transduction-related kinases. Efflux studies showed that other transporter types were functional in the APC; they appeared to be altered dynamically in threonine-deficient cells in response to rapid increases in system A activity. The present data provided support for the chemical sensitivity of the APC and its role as the brain area housing the indispensable amino acid chemosensor. They also showed a region-specific, phosphorylation-dependent activation of the system A transporter in the brain in response to threonine deficiency.

  15. TNF-α stimulates System A amino acid transport in primary human trophoblast cells mediated by p38 MAPK signaling.

    PubMed

    Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

    2015-10-01

    Maternal obesity and gestational diabetes mellitus (GDM) increase the risk of delivering infants that are large for gestational age with greater adiposity, who are prone to the development of metabolic disease in childhood and beyond. These maternal conditions are also associated with increased levels of the proinflammatory cytokine TNF-α in maternal tissues and the placenta. Recent evidence suggests that changes in placental amino acid transport contribute to altered fetal growth. TNF-α was previously shown to stimulate System A amino acid transport in primary human trophoblasts (PHTs), however the molecular mechanisms remain unknown. In this study, we tested the hypothesis that TNF-α regulates amino acid uptake in cultured PHTs by a mitogen-activated protein kinase (MAPK)-dependent mechanism. Treatment of PHTs with TNF-α significantly increased System A amino acid transport, as well as Erk and p38 MAPK signaling. Pharmacological antagonism of p38, but not Erk MAPK activity, inhibited TNF-α stimulated System A activity. Silencing of p38 MAPK using siRNA transfections prevented TNF-α stimulated System A transport in PHTs. TNF-α significantly increased the protein expression of System A transporters SNAT1 and SNAT2, but did not affect their mRNA expression. The effects of TNF-α on SNAT1 and SNAT2 protein expression were reversed by p38 MAPK siRNA silencing. In conclusion, TNF-α regulates System A activity through increased SNAT1 and SNAT2 transporter protein expression in PHTs. These findings suggest that p38 MAPK may represent a critical mechanistic link between elevated proinflammatory cytokines and increased placental amino acid transport in obese and GDM pregnancies associated with fetal overgrowth.

  16. TNF-α stimulates System A amino acid transport in primary human trophoblast cells mediated by p38 MAPK signaling.

    PubMed

    Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

    2015-10-01

    Maternal obesity and gestational diabetes mellitus (GDM) increase the risk of delivering infants that are large for gestational age with greater adiposity, who are prone to the development of metabolic disease in childhood and beyond. These maternal conditions are also associated with increased levels of the proinflammatory cytokine TNF-α in maternal tissues and the placenta. Recent evidence suggests that changes in placental amino acid transport contribute to altered fetal growth. TNF-α was previously shown to stimulate System A amino acid transport in primary human trophoblasts (PHTs), however the molecular mechanisms remain unknown. In this study, we tested the hypothesis that TNF-α regulates amino acid uptake in cultured PHTs by a mitogen-activated protein kinase (MAPK)-dependent mechanism. Treatment of PHTs with TNF-α significantly increased System A amino acid transport, as well as Erk and p38 MAPK signaling. Pharmacological antagonism of p38, but not Erk MAPK activity, inhibited TNF-α stimulated System A activity. Silencing of p38 MAPK using siRNA transfections prevented TNF-α stimulated System A transport in PHTs. TNF-α significantly increased the protein expression of System A transporters SNAT1 and SNAT2, but did not affect their mRNA expression. The effects of TNF-α on SNAT1 and SNAT2 protein expression were reversed by p38 MAPK siRNA silencing. In conclusion, TNF-α regulates System A activity through increased SNAT1 and SNAT2 transporter protein expression in PHTs. These findings suggest that p38 MAPK may represent a critical mechanistic link between elevated proinflammatory cytokines and increased placental amino acid transport in obese and GDM pregnancies associated with fetal overgrowth. PMID:26508738

  17. Uptake of sialic acid by human erythrocyte. Characterization of a transport system.

    PubMed

    Bulai, Tatiana; Bratosin, Daniela; Artenie, Vlad; Montreuil, Jean

    2003-01-01

    Upon incubation of human red blood cells (RBC) with [4-9-14C] N-acetylneuraminic acid, the cells incorporated this sugar, as demonstrated by the identification of labelled N-acetylmannosamine in the cytosol, as a result of the action of the sialic acid pyruvate-lyase we discovered previously (Biochimie 84 (2002) 655). The mechanism is saturable and indicates the presence of a limited number of transporter molecules in the RBC membrane. This transport process may have relevance to the desialylation of membrane glycoconjugates which occurs during ageing of erythrocytes.

  18. Transforming growth factor-beta 1 stimulates vascular smooth muscle cell L-proline transport by inducing system A amino acid transporter 2 (SAT2) gene expression.

    PubMed Central

    Ensenat, D; Hassan, S; Reyna, S V; Schafer, A I; Durante, W

    2001-01-01

    Transforming growth factor-beta1 (TGF-beta 1) is a multifunctional cytokine that contributes to arterial remodelling by stimulating vascular smooth muscle cell (SMC) growth and collagen synthesis at sites of vascular injury. Since l-proline is essential for the synthesis of collagen, we examined whether TGF-beta 1 regulates the transcellular transport of l-proline by vascular SMCs. l-Proline uptake by vascular SMCs was primarily sodium-dependent, pH-sensitive, blocked by neutral amino acids and alpha-(methylamino)isobutyric acid, and exhibited trans-inhibition. Treatment of SMCs with TGF-beta 1 stimulated l-proline transport in a concentration- and time-dependent manner. The TGF-beta 1-mediated l-proline uptake was inhibited by cycloheximide or actinomycin D. Kinetic studies indicated that TGF-beta 1-induced l-proline transport was mediated by an increase in transport capacity independent of any changes in the affinity for l-proline. TGF-beta 1 stimulated the expression of system A amino acid transporter 2 (SAT2) mRNA in a time-dependent fashion that paralleled the increase in l-proline transport. Reverse transcriptase PCR failed to detect the presence of SAT1 or amino acid transporter 3 (ATA3) in either untreated or TGF-beta 1-treated SMCs. These results demonstrate that l-proline transport by vascular SMCs is mediated predominantly by the SAT and that TGF-beta 1 stimulates SMC l-proline uptake by inducing the expression of the SAT2 gene. The ability of TGF-beta 1 to induce SAT2 expression may function to provide SMCs with the necessary levels of l-proline required for collagen synthesis and cell growth. PMID:11716780

  19. Ascorbic acid transport into cultured pituitary cells

    SciTech Connect

    Cullen, E.I.; May, V.; Eipper, R.A.

    1986-05-01

    An amidating enzyme designated peptidyl-glycine ..cap alpha..-amidating monooxygenase (PAM) has been studied in a variety of tissues and is dependent on molecular oxygen and stimulated by copper and ascorbic acid. To continue investigating the relationship among cellular ascorbic acid concentrations, amidating ability, and PAM activity, the authors studied ascorbic acid transport in three cell preparations that contain PAM and produce amidated peptides: primary cultures of rat anterior and intermediate pituitary and mouse AtT-20 tumor cells. When incubated in 50 ..mu..M (/sup 14/C)ascorbic acid all three cell preparations concentrated ascorbic acid 20- to 40-fold, producing intracellular ascorbate concentrations of 1 to 2 mM, based on experimentally determined cell volumes. All three cell preparations displayed saturable ascorbic acid uptake with half-maximal initial rates occurring between 9 and 18 ..mu..M ascorbate. Replacing NaCl in the uptake buffer with choline chloride significantly diminished ascorbate uptake in all three preparations. Ascorbic acid efflux from these cells was slow, displaying half-lives of 7 hours. Unlike systems that transport dehydroascorbic acid, the transport system for ascorbic acid in these cells was not inhibited by glucose. Thus, ascorbate is transported into pituitary cells by a sodium-dependent, active transport system.

  20. Geochemical Controls on the Partitioning and Hydrological Transport of Metals in a Human Impacted, Non-Acidic, River System

    NASA Astrophysics Data System (ADS)

    Thorslund, J.; Jarsjo, J.; Wällstedt, T.; Morth, C. M.; Lychagin, M.; Chalov, S.

    2014-12-01

    The knowledge of coupled processes controlling the spreading and fate of metals in non-acidic river systems is currently much more limited than the knowledge of metal behavior under acidic conditions (e.g., in acid mine drainage systems). Critical geochemical controls governing metal speciation may thus differ substantially between acidic and non-acidic hydrological systems. We here aim at expanding the knowledge of metals in non-acidic river systems, by considering a high pH river, influenced by mining by the largest gold mining area in the Mongolian part of the transboundary Lake Baikal drainage basin. The combined impact of geochemical and hydrological processes is investigated, to be able to understand the solubility of various heavy metals, their partitioning between particulate and dissolved phase and its impact on overall transport. We show, through site specific measurements and a geochemical modelling approach, that the combined effects of precipitation of ferrihydrite and gibbsite and associated sorption complexes of several metals can explain the high impact of suspended transport relative to total transport often seen under non-acidic conditions. Our results also identifies the phosphate mineral Hydroxyapatite as a potential key sorption site for many metals, which has both site specific and general relevance for metal partitioning under non-acidic conditions. However, an adsorption database, which is currently unavailable for hydroxyapatite, needs to be developed for appropriate sorption quantification. Furthermore, Cd, Fe, Pb and Zn were particularly sensitive to increasing DOC concentrations, which increased the solubility of these metals due to metal-organic complexation. Modeling the sensitivity to changes in geochemical parameters showed that decreasing pH and increasing DOC concentrations in downstream regions would increase the dissolution and hence the toxicity and bioavailability of many pollutants of concern in the downstream ecosystem. In

  1. Amino acid transport systems beta and A in fetal T lymphocytes in intrauterine growth restriction and with tumor necrosis factor-alpha treatment.

    PubMed

    Iruloh, Chibuike G; D'Souza, Stephen W; Fergusson, William D; Baker, Philip N; Sibley, Colin P; Glazier, Jocelyn D

    2009-01-01

    Intrauterine growth restriction (IUGR) is associated with reduced activity of placental amino acid transport systems beta and A. Whether this phenotype is maintained in fetal cells outside the placenta is unknown. In IUGR, cord blood tumor necrosis factor (TNF)-alpha concentrations are raised, potentially influencing amino acid transport in fetal cells. We used fetal T lymphocytes as a model to study systems beta and A amino acid transporters in IUGR compared with normal pregnancy. We also studied the effect of TNF-alpha on amino acid transporter activity. In fetal lymphocytes from IUGR pregnancies, taurine transporter mRNA expression encoding system beta transporter was reduced, but there was no change in system beta activity. No significant differences were observed in system A mRNA expression (encoding SNAT1 and SNAT2) or system A activity between the two groups. After 24 or 48 h TNF-alpha treatment, fetal T lymphocytes from normal pregnancies showed no significant change in system A or system beta activity, although cell viability was compromised. This study represents the first characterization of amino acid transport in a fetal cell outside the placenta in IUGR. We conclude that the reduced amino acid transporter activity found in placenta in IUGR is not a feature of all fetal cells.

  2. Coupled transport protein systems.

    PubMed

    Thatcher, Jack D

    2013-04-16

    This set of animated lessons provides examples of how transport proteins interact in coupled systems to produce physiologic effects. The gastric pumps animation depicts the secretion of hydrochloric acid into the gastric lumen. The animation called glucose absorption depicts glucose absorption by intestinal epithelial cells. The CFTR animation explains how the cystic fibrosis conductance transmembrane regulator (CFTR) functions as a key component of a coupled system of transport proteins that clears the pulmonary system of mucus and inhaled particulates. These animations serve as valuable resources for any collegiate-level course that describes these processes. Courses that might use them include introductory biology, biochemistry, biophysics, cell biology, pharmacology, and physiology.

  3. Pharmacology of Glutamate Transport in the CNS: Substrates and Inhibitors of Excitatory Amino Acid Transporters (EAATs) and the Glutamate/Cystine Exchanger System x c -

    NASA Astrophysics Data System (ADS)

    Bridges, Richard J.; Patel, Sarjubhai A.

    As the primary excitatory neurotransmitter in the mammalian CNS, l-glutamate participates not only in standard fast synaptic communication, but also contributes to higher order signal processing, as well as neuropathology. Given this variety of functional roles, interest has been growing as to how the extracellular concentrations of l-glutamate surrounding neurons are regulated by cellular transporter proteins. This review focuses on two prominent systems, each of which appears capable of influencing both the signaling and pathological actions of l-glutamate within the CNS: the sodium-dependent excitatory amino acid transporters (EAATs) and the glutamate/cystine exchanger, system x c - (Sx c -). While the family of EAAT subtypes limit access to glutamate receptors by rapidly and efficiently sequestering l-glutamate in neurons and glia, Sxc - provides a route for the export of glutamate from cells into the extracellular environment. The primary intent of this work is to provide an overview of the inhibitors and substrates that have been developed to delineate the pharmacological specificity of these transport systems, as well as be exploited as probes with which to selectively investigate function. Particular attention is paid to the development of small molecule templates that mimic the structural properties of the endogenous substrates, l-glutamate, l-aspartate and l-cystine and how strategic control of functional group position and/or the introduction of lipophilic R-groups can impact multiple aspects of the transport process, including: subtype selectivity, inhibitory potency, and substrate activity.

  4. System A Amino Acid Transport-Targeted Brain and Systemic Tumor PET Imaging Agents 2-Amino-3-[18F]Fluoro-2-Methylpropanoic Acid and 3-[18F]Fluoro-2-Methyl-2-(Methylamino)propanoic Acid

    PubMed Central

    Yu, Weiping; McConathy, Jonathan; Olson, Jeffrey J.; Goodman, Mark M.

    2014-01-01

    Introduction Amino acid based radiotracers target tumor cells through increased uptake by membrane-associated amino acid transport (AAT) systems. In the present study, four structurally related non-natural 18F-labeled amino acids, (R)- and (S)-[18F]FAMP 1 and (R)- and (S)-[18F]MeFAMP 2 have been prepared and evaluated in vitro and in vivo for their potential utility in brain and systemic tumor imaging based upon primarily system A transport with positron emission tomography (PET). Methods The transport of enantiomers of [18F]FAMP 1 and [18F]MeFAMP 2 was measured through in vitro uptake assays in human derived cancer cells including A549 (lung), DU145 (prostate), SKOV3 (ovary), MDA MB468 (breast) and U87 (brain) in the presence and absence of amino acid transporter inhibitors. The in vivo biodistribution of these tracers was evaluated using tumor mice xenografts at 15, 30, 60 and 120 min post injection. Results All four tracers showed moderate to high levels of uptake (1- 9 %ID/5×105 cells) by the cancer cell lines tested in vitro. AAT cell inhibition assays demonstrated that (R)-[18F]1 and (S)-[18F]1 entered these tumor cells via mixed AATs, likely but not limited to system A and system L. In contrast, (R)-[18F]2 and (S)-[18F]2 showed high selectivity for system A AAT. Similar to the results of in vitro cell studies, the tumor uptake of all four tracers was good to high and persisted over the 2 hours time course of in vivo studies. The accumulation of these tracers was higher in tumor than most normal tissues including blood, brain, muscle, bone, heart, and lung, and the tracers with the highest in vitro selectivity for system A AAT generally demonstrated the best tumor imaging properties. Higher uptake of these tracers was observed in the pancreas, kidney and spleen compared to tumors. Conclusions These preclinical studies demonstrate good imaging properties in a wide range of tumors for all four amino acids evaluated with (R)-[18F]2 having the highest

  5. Acid rain: chemistry and transport.

    PubMed

    Irwin, J G; Williams, M L

    1988-01-01

    This review describes the more important features of the emission, chemistry, transport and deposition of pollutants involved in acid deposition. Global emissions, both natural and man-made, of sulphur and nitrogen oxides are discussed and examples of spatial distributions and trends over the last century presented. The more significant chemical and physical processes involved in the transformation of the primary emissions into their acidic end products are described, including a summary of the approximate timescales of the processes involved. Measurements and modelled calculations of spatial and temporal patterns in the deposition of acidic pollutants by both wet and dry pathways are presented.

  6. System A amino acid transporter SNAT2 shows subtype-specific affinity for betaine and hyperosmotic inducibility in placental trophoblasts.

    PubMed

    Nishimura, Tomohiro; Yagi, Risa; Usuda, Mariko; Oda, Kenji; Yamazaki, Mai; Suda, Sayaka; Takahashi, Yu; Okazaki, Fumiyasu; Sai, Yoshimichi; Higuchi, Kei; Maruyama, Tetsuo; Tomi, Masatoshi; Nakashima, Emi

    2014-05-01

    Betaine uptake is induced by hypertonic stress in a placental trophoblast cell line, and involvement of amino acid transport system A was proposed. Here, we aimed to identify the subtype(s) of system A that mediates hypertonicity-induced betaine uptake. Measurement of [(14)C]betaine uptake by HEK293 cells transiently transfected with human or rat sodium-coupled neutral amino acid transporters (SNATs), SNAT1, SNAT2 and SNAT4 revealed that only human and rat SNAT2 have betaine uptake activity. The Michaelis constants (Km) of betaine uptake by human and rat SNAT2 were estimated to be 5.3 mM and 4.6 mM, respectively. Betaine exclusively inhibited the uptake activity of SNAT2 among the rat system A subtypes. We found that rat SNAT1, SNAT2 and SNAT4 were expressed at the mRNA level under isotonic conditions, while expression of SNAT2 and SNAT4 was induced by hypertonicity in TR-TBT 18d-1 cells. Western blot analyses revealed that SNAT2 expression on plasma membrane of TR-TBT 18d-1 cells was more potently induced by hypertonicity than that in total cell lysate. Immunocytochemistry confirmed the induction of SNAT2 expression in TR-TBT 18d-1 cells exposed to hypertonic conditions and indicated that SNAT2 was localized on the plasma membrane in these cells. Our results indicate that SNAT2 transports betaine, and that tonicity-sensitive SNAT2 expression may be involved in regulation of betaine concentration in placental trophoblasts. PMID:24434061

  7. System A amino acid transporter SNAT2 shows subtype-specific affinity for betaine and hyperosmotic inducibility in placental trophoblasts.

    PubMed

    Nishimura, Tomohiro; Yagi, Risa; Usuda, Mariko; Oda, Kenji; Yamazaki, Mai; Suda, Sayaka; Takahashi, Yu; Okazaki, Fumiyasu; Sai, Yoshimichi; Higuchi, Kei; Maruyama, Tetsuo; Tomi, Masatoshi; Nakashima, Emi

    2014-05-01

    Betaine uptake is induced by hypertonic stress in a placental trophoblast cell line, and involvement of amino acid transport system A was proposed. Here, we aimed to identify the subtype(s) of system A that mediates hypertonicity-induced betaine uptake. Measurement of [(14)C]betaine uptake by HEK293 cells transiently transfected with human or rat sodium-coupled neutral amino acid transporters (SNATs), SNAT1, SNAT2 and SNAT4 revealed that only human and rat SNAT2 have betaine uptake activity. The Michaelis constants (Km) of betaine uptake by human and rat SNAT2 were estimated to be 5.3 mM and 4.6 mM, respectively. Betaine exclusively inhibited the uptake activity of SNAT2 among the rat system A subtypes. We found that rat SNAT1, SNAT2 and SNAT4 were expressed at the mRNA level under isotonic conditions, while expression of SNAT2 and SNAT4 was induced by hypertonicity in TR-TBT 18d-1 cells. Western blot analyses revealed that SNAT2 expression on plasma membrane of TR-TBT 18d-1 cells was more potently induced by hypertonicity than that in total cell lysate. Immunocytochemistry confirmed the induction of SNAT2 expression in TR-TBT 18d-1 cells exposed to hypertonic conditions and indicated that SNAT2 was localized on the plasma membrane in these cells. Our results indicate that SNAT2 transports betaine, and that tonicity-sensitive SNAT2 expression may be involved in regulation of betaine concentration in placental trophoblasts.

  8. Glycinergic-Fipronil Uptake Is Mediated by an Amino Acid Carrier System and Induces the Expression of Amino Acid Transporter Genes in Ricinus communis Seedlings.

    PubMed

    Xie, Yun; Zhao, Jun-Long; Wang, Chuan-Wei; Yu, Ai-Xin; Liu, Niu; Chen, Li; Lin, Fei; Xu, Han-Hong

    2016-05-18

    Phloem-mobile insecticides are efficient for piercing and sucking insect control. Introduction of sugar or amino acid groups to the parent compound can improve the phloem mobility of insecticides, so a glycinergic-fipronil conjugate (GlyF), 2-(3-(3-cyano-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-((trifluoromethyl)sulfinyl)-1H-pyrazole-5-yl)ureido) acetic acid, was designed and synthesized. Although the "Kleier model" predicted that this conjugate is not phloem mobile, GlyF can be continually detected during a 5 h collection of Ricinus communis phloem sap. Furthermore, an R. communis seedling cotyledon disk uptake experiment demonstrates that the uptake of GlyF is sensitive to pH, carbonyl cyanide m-chlorophenylhydrazone (CCCP), temperature, and p-chloromercuribenzenesulfonic acid (pCMBS) and is likely mediated by amino acid carrier system. To explore the roles of amino acid transporters (AATs) in GlyF uptake, a total of 62 AAT genes were identified from the R. communis genome in silico. Phylogenetic analysis revealed that AATs in R. communis were organized into the ATF (amino acid transporter) and APC (amino acid, polyaminem and choline transporter) superfamilies, with five subfamilies in ATF and two in APC. Furthermore, the expression profiles of 20 abundantly expressed AATs (cycle threshold (Ct) values <27) were analyzed at 1, 3, and 6 h after GlyF treatment by RT-qPCR. The results demonstrated that expression levels of four AAT genes, RcLHT6, RcANT15, RcProT2, and RcCAT2, were induced by the GlyF treatment in R. communis seedlings. On the basis of the observation that the expression profile of the four candidate genes is similar to the time course observation for GlyF foliar disk uptake, it is suggested that those four genes are possible candidates involved in the uptake of GlyF. These results contribute to a better understanding of the mechanism of GlyF uptake as well as phloem loading from a molecular biology perspective and facilitate functional

  9. Isolation of plasma membrane vesicles from mouse placenta at term and measurement of system A and system beta amino acid transporter activity.

    PubMed

    Kusinski, L C; Jones, C J P; Baker, P N; Sibley, C P; Glazier, J D

    2010-01-01

    Placental amino acid transport is essential for optimal fetal growth and development, with a reduced fetal provision of amino acids being implicated as a potential cause of fetal growth restriction (FGR). Understanding placental insufficiency related FGR has been aided by the development of mouse models that have features of the human disease. However, to take maximal advantage of these, methods are required to study placental function in the mouse. Here, we report a method to isolate plasma membrane vesicles from mouse placenta near-term and have used these to investigate two amino acid transporters, systems A and beta, the activities of which are reduced in human placental microvillous plasma membrane (MVM) vesicles from FGR pregnancies. Plasma membrane vesicles were isolated at embryonic day 18 by a protocol involving homogenisation, MgCl(2) precipitation and centrifugation. Vesicles were enriched 11.3+/-0.5-fold in alkaline phosphatase activity as compared to initial homogenate, with minimal intracellular organelle contamination as judged by marker analyses. Cytochemistry revealed alkaline phosphatase was localised between trophoblast layers I and II, with intense reaction product deposited on the maternal-facing plasma membrane of layer II, suggesting that vesicles were derived from this trophoblast membrane. System A and system beta activity in mouse placental vesicles, measured as Na(+)-dependent uptake of (14)C-methylaminoisobutyric acid (MeAIB) and (3)H-taurine respectively confirmed localisation of these transporters to the maternal-facing plasma membrane of layer II. Comparison to human placental MVM showed that system A activity was comparable at initial rate between species whilst system beta activity was significantly lower in mouse. This mirrored the lower expression of TAUT observed in mouse placental vesicles. We conclude that syncytiotrophoblast layer II-derived plasma membrane vesicles can be isolated and used to examine transporter function.

  10. The EGF Receptor Promotes the Malignant Potential of Glioma by Regulating Amino Acid Transport System xc(-).

    PubMed

    Tsuchihashi, Kenji; Okazaki, Shogo; Ohmura, Mitsuyo; Ishikawa, Miyuki; Sampetrean, Oltea; Onishi, Nobuyuki; Wakimoto, Hiroaki; Yoshikawa, Momoko; Seishima, Ryo; Iwasaki, Yoshimi; Morikawa, Takayuki; Abe, Shinya; Takao, Ayumi; Shimizu, Misato; Masuko, Takashi; Nagane, Motoo; Furnari, Frank B; Akiyama, Tetsu; Suematsu, Makoto; Baba, Eishi; Akashi, Koichi; Saya, Hideyuki; Nagano, Osamu

    2016-05-15

    Extracellular free amino acids contribute to the interaction between a tumor and its microenvironment through effects on cellular metabolism and malignant behavior. System xc(-) is composed of xCT and CD98hc subunits and functions as a plasma membrane antiporter for the uptake of extracellular cystine in exchange for intracellular glutamate. Here, we show that the EGFR interacts with xCT and thereby promotes its cell surface expression and function in human glioma cells. EGFR-expressing glioma cells manifested both enhanced antioxidant capacity as a result of increased cystine uptake, as well as increased glutamate, which promotes matrix invasion. Imaging mass spectrometry also revealed that brain tumors formed in mice by human glioma cells stably overexpressing EGFR contained higher levels of reduced glutathione compared with those formed by parental cells. Targeted inhibition of xCT suppressed the EGFR-dependent enhancement of antioxidant capacity in glioma cells, as well as tumor growth and invasiveness. Our findings establish a new functional role for EGFR in promoting the malignant potential of glioma cells through interaction with xCT at the cell surface. Cancer Res; 76(10); 2954-63. ©2016 AACR.

  11. Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

    PubMed

    Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

    2013-12-01

    Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1β (10pg/ml) for 24h. IL-1β increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor β expression. Furthermore, IL-1β inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1β alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1β treatment. Moreover, IL-1β inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1β inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1β levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth.

  12. Transport of coenzyme M (2-mercaptoethanesulfonic acid) and methylcoenzyme M [(2-methylthio)ethanesulfonic acid] in Methanococcus voltae: identification of specific and general uptake systems.

    PubMed Central

    Dybas, M; Konisky, J

    1989-01-01

    A transport system for coenzyme M (2-mercaptoethanesulfonic acid [HS-CoM]) and methylcoenzyme M [(2-(methylthio)ethanesulfonic acid (CH3-S-CoM)] in Methanococcus voltae required energy, showed saturation kinetics, and concentrated both forms of coenzyme M against a concentration gradient. Transport required hydrogen and carbon dioxide for maximal uptake. CH3-S-CoM uptake was inhibited by N-ethylmaleimide and monensin. Both HS-CoM and CH3-S-CoM uptake showed sodium dependence. In wild-type M. voltae, HS-CoM uptake was concentration dependent, with a Vmax of 960 pmol/min per mg of protein and an apparent Km of 61 microM. Uptake of CH3-S-CoM showed a Vmax of 88 pmol/min per mg of protein and a Km of 53 microM. A mutant of M. voltae resistant to the coenzyme M analog 2-bromoethanesulfonic acid (BES) showed no uptake of CH3-S-CoM but accumulated HS-CoM at the wild-type rate. While the higher-affinity uptake system was specific for HS-CoM, the lower-affinity system mediated uptake of HS-CoM, CH3-S-CoM, and BES. Analysis of the intracellular coenzyme M pools in metabolizing cells showed an intracellular HS-CoM concentration of 14.8 mM and CH3-S-CoM concentration of 0.21 mM. PMID:2509421

  13. Uric acid transport and disease

    PubMed Central

    So, Alexander; Thorens, Bernard

    2010-01-01

    Uric acid is the metabolic end product of purine metabolism in humans. It has antioxidant properties that may be protective but can also be pro-oxidant, depending on its chemical microenvironment. Hyperuricemia predisposes to disease through the formation of urate crystals that cause gout, but hyperuricemia, independent of crystal formation, has also been linked with hypertension, atherosclerosis, insulin resistance, and diabetes. We discuss here the biology of urate metabolism and its role in disease. We also cover the genetics of urate transport, including URAT1, and recent studies identifying SLC2A9, which encodes the glucose transporter family isoform Glut9, as a major determinant of plasma uric acid levels and of gout development. PMID:20516647

  14. Characterization of 2-aminoisobutyric acid transport in Neurospora crassa: a general amino acid permease-specific substrate.

    PubMed Central

    Ogilvie-Villa, S; DeBusk, R M; DeBusk, A G

    1981-01-01

    We report the characterization of an amino acid 2-aminoisobutyric acid was transported solely by the general amino acid permease and not by the neutral amino acid permease. Furthermore, this substrate was not metabolized after transport. The potential for a system-specific nonmetabolizable substrate as a tool in the analysis of amino acid transport and its regulation is discussed. PMID:6456264

  15. Water transport in water-in-oil-in-water liquid emulsion membrane system for the separation of lactic acid

    SciTech Connect

    Mok, Y.S.; Lee, W.K. )

    1994-03-01

    Liquid emulsion membranes (LEMs) were applied to the separation of lactic acid from an aqueous feed phase, and water transport (swelling) was investigated during the separation. Considering that as lactic acid was extracted into the internal stripping phase, osmotic pressure difference across the membrane was varied, the water transfer coefficient was evaluated. The water transfer coefficient was larger at higher carrier concentration and initial lactic acid concentration, which means that emulsion swelling can also be mediated by solute/carrier complexes although it is, in general, osmotically induced. The appropriate LEM formulation was given for separation and concentration of lactic acid. If both separation and concentration are desired, evidently emulsion swelling should be considered in conjunction with the transport rate of lactic acid. It was observed that the separated solute concentration in the internal phase was lowered due to swelling during the operation. Nevertheless, lactic acid could be concentrated in the internal phase more than 6 times in specific conditions, indicating that as the volume ratio of external phase to internal phase is increased, a still higher concentration in the internal phase can be obtained. 22 refs., 10 figs., 4 tabs.

  16. Transportation System Requirements Document

    SciTech Connect

    Not Available

    1993-09-01

    This Transportation System Requirements Document (Trans-SRD) describes the functions to be performed by and the technical requirements for the Transportation System to transport spent nuclear fuel (SNF) and high-level radioactive waste (HLW) from Purchaser and Producer sites to a Civilian Radioactive Waste Management System (CRWMS) site, and between CRWMS sites. The purpose of this document is to define the system-level requirements for Transportation consistent with the CRWMS Requirement Document (CRD). These requirements include design and operations requirements to the extent they impact on the development of the physical segments of Transportation. The document also presents an overall description of Transportation, its functions, its segments, and the requirements allocated to the segments and the system-level interfaces with Transportation. The interface identification and description are published in the CRWMS Interface Specification.

  17. Modeling Electrical Transport through Nucleic Acids

    NASA Astrophysics Data System (ADS)

    Qi, Jianqing

    Nucleic acids play a vital role in many biological systems and activities. In recent years, engineers and scientists have been interested in studying their electrical properties. The motivation for these studies stems from the following facts: (1) the bases, which form the building blocks of nucleic acids, have unique ionization potentials. Further, nucleic acids are one of the few nanomaterials that can be reproducibly manufactured with a high degree of accuracy (though admittedly their placement at desired locations remains a challenge). As a result, designed strands with specific sequences may offer unique device properties; (2) electrical methods offer potential for sequencing nucleic acids based on a single molecule; (3) electrical methods for disease detection based on the current flowing through nucleic acids are beginning to be demonstrated. While experiments in the above mentioned areas is promising, a deeper understanding of the electrical current flow through the nucleic acids needs to be developed. The modeling of current flowing in these molecules is complex because: (1) they are based on atomic scale contacts between nucleic acids and metal, which cannot be reproducibly built; (2) the conductivity of nucleic acids is easily influenced by the environment, which is constantly changing; and (3) the nucleic acids by themselves are floppy. This thesis focuses on the modeling of electrical transport through nucleic acids that are connected to two metal electrodes at nanoscale. We first develop a decoherent transport model for the double-stranded helix based on the Landauer-Buttiker framework. This model is rationalized by comparison with an experiment that measured the conductance of four different DNA strands. The developed model is then used to study the: (1) potential to make barriers and wells for quantum transport using specifically engineered sequences; (2) change in the electrical properties of a specific DNA strand with and without methylation; (3

  18. Palmitate activation by fatty acid transport protein 4 as a model system for hepatocellular apoptosis and steatosis.

    PubMed

    Seeßle, Jessica; Liebisch, Gerhard; Schmitz, Gerd; Stremmel, Wolfgang; Chamulitrat, Walee

    2015-05-01

    Fatty acid transport protein (FATP) 4 is a minor FATP in the liver but it has some activity towards palmitate 16:0 (Pal). We here chose FATP4 as a representative model enzyme for acyl-CoA synthetases (ACSs), and FATPs to determine whether Pal activation would lead to apoptosis and alteration in lipid metabolism. By using FATP4 overexpressed (FATP4) Huh-7 cells, we showed that FATP4 was localized in the endoplasmic reticulum (ER) and mitochondria of FATP4 cells. FATP4 cells were more responsive to Pal than the control GFP cells in increasing palmitoyl-CoA and oleoyl-CoA activities as well as apoptosis by ~2-3 folds. The lipoapoptosis susceptibility by FATP4 was coupled with the increased JNK, PUMA, caspase3, PARP-1 activation as well as Rac-1-mediated cytoskeletal reorganization, and decreased insulin sensitivity. This was associated with increased contents of neutral lipids and significant alteration in composition of phospholipids and sphingolipids including increased lysophosphatidylcholine (LPC), ceramide, and hexosylceramide, as well as an increase of saturated:polyunsaturated fatty acid ratio in LPC and PC, but a decrease of this ratio in phosphatidylethanolamine pool. By use of ceramide synthase inhibitors, our results showed that FATP4-sensitized lipoapoptosis was not mediated by ceramides. Moreover, FATP4 expression was increased in fatty livers in vivo. Thus, our model system has provided a clue that Pal activation FATP4 triggers hepatocellular apoptosis via altered phospholipid composition and steatosis by acylation into complex lipids. This may be a redundant mechanism for other ER-localizing ACSs and FATPs in the liver, and hence their involvement in the development of fatty liver disease.

  19. Transepithelial transport of ferulic acid by monocarboxylic acid transporter in Caco-2 cell monolayers.

    PubMed

    Konishi, Yutaka; Shimizu, Makoto

    2003-04-01

    Our previous study (Biosci. Biotechnol. Biochem., 66, 2449-2457 (2002)), suggested that ferulic acid was transported via a monocarboxylic acid transporter (MCT). Transepithelial transport of ferulic acid was examined in this study by directly measuring the rate of its transport across Caco-2 cell monolayers. Ferulic acid transport was dependent on pH, and in a vectorical way in the apical-basolateral direction. The permeation of ferulic acid was concentration-dependent and saturable; the Michaelis constant was 16.2 mM and the maximum velocity was 220.4 nmol min-1 (mg protein)-1. Various substrates for MCTs, such as benzoic acid and acetic acid, strongly inhibited the permeation of ferulic acid, demonstrating that ferulic acid is obviously transported by MCT. Antioxidative phenolic acid compounds from dietary sources like ferulic acid would be recognized and transported by MCT by intestinal absorption.

  20. Subseabed disposal transportation system

    SciTech Connect

    Allen, Jr., G. C.; Vernon, M. E.; Anderson, D. R.

    1980-01-01

    Transportation requirements and interfaces are being considered in the evaluation of the seabed disposal option. Technical direction and planning are on-going to ensure the development of major transportation systems in support of the seabed disposal option. Factors which affect the risk and effectiveness of transportation are being included in site selection criteria. However, detailed development of port facilities and transport/emplacement equipment is still several years into the future. (DMC)

  1. Methylarsonous acid transport by aquaglyceroporins.

    PubMed

    Liu, Zijuan; Styblo, Miroslav; Rosen, Barry P

    2006-04-01

    Many mammals methylate trivalent inorganic arsenic in liver to species that are released into the bloodstream and excreted in urine and feces. This study addresses how methylated arsenicals pass through cell membranes. We have previously shown that aquaglyceroporin channels, including Escherichia coli GlpF, Saccharomyces cerevisiae Fps1p, AQP7, and AQP9 from rat and human, conduct trivalent inorganic arsenic [As(III)] as arsenic trioxide, the protonated form of arsenite. One of the initial products of As(III) methylation is methylarsonous acid [MAs(III)], which is considerably more toxic than inorganic As(III). In this study, we investigated the ability of GlpF, Fps1p, and AQP9 to facilitate movement of MAs(III) and found that rat aquaglyceroporin conducted MAs(III) at a higher rate than the yeast homologue. In addition, rat AQP9 facilitates MAs(III) at a higher rate than As(III). These results demonstrate that aquaglyceroporins differ both in selectivity for and in transport rates of trivalent arsenicals. In this study, the requirement of AQP9 residues Phe-64 and Arg-219 for MAs(III) movement was examined. A hydrophobic residue at position 64 is not required for MAs(III) transport, whereas an arginine at residue 219 may be required. This is similar to that found for As(III), suggesting that As(III) and MAs(III) use the same translocation pathway in AQP9. Identification of MAs(III) as an AQP9 substrate is an important step in understanding physiologic responses to arsenic in mammals, including humans.

  2. Payload transportation system study

    NASA Technical Reports Server (NTRS)

    1976-01-01

    A standard size set of shuttle payload transportation equipment was defined that will substantially reduce the cost of payload transportation and accommodate a wide range of payloads with minimum impact on payload design. The system was designed to accommodate payload shipments between the level 4 payload integration sites and the launch site during the calendar years 1979-1982. In addition to defining transportation multi-use mission support equipment (T-MMSE) the mode of travel, prime movers, and ancillary equipment required in the transportation process were also considered. Consistent with the STS goals of low cost and the use of standardized interfaces, the transportation system was designed to commercial grade standards and uses the payload flight mounting interfaces for transportation. The technical, cost, and programmatic data required to permit selection of a baseline system of MMSE for intersite movement of shuttle payloads were developed.

  3. Space Transportation Propulsion Systems

    NASA Technical Reports Server (NTRS)

    Liou, Meng-Sing; Stewart, Mark E.; Suresh, Ambady; Owen, A. Karl

    2001-01-01

    This report outlines the Space Transportation Propulsion Systems for the NPSS (Numerical Propulsion System Simulation) program. Topics include: 1) a review of Engine/Inlet Coupling Work; 2) Background/Organization of Space Transportation Initiative; 3) Synergy between High Performance Computing and Communications Program (HPCCP) and Advanced Space Transportation Program (ASTP); 4) Status of Space Transportation Effort, including planned deliverables for FY01-FY06, FY00 accomplishments (HPCCP Funded) and FY01 Major Milestones (HPCCP and ASTP); and 5) a review current technical efforts, including a review of the Rocket-Based Combined-Cycle (RBCC), Scope of Work, RBCC Concept Aerodynamic Analysis and RBCC Concept Multidisciplinary Analysis.

  4. Smart vehicular transportation systems

    SciTech Connect

    Little, C.Q.; Wilson, C.W.

    1997-05-01

    This work builds upon established Sandia intelligent systems technology to develop a unique approach for the integration of intelligent system control into the US Highway and urban transportation systems. The Sandia developed concept of the COPILOT controller integrates a human driver with computer control to increase human performance while reducing reliance on detailed driver attention. This research extends Sandia expertise in sensor based, real-time control of robotics systems to high speed transportation systems. Knowledge in the form of maps and performance characteristics of vehicles provides the automatic decision making intelligence needed to plan optimum routes, maintain safe driving speeds and distances, avoid collisions, and conserve fuel.

  5. Intercellular transport of lysosomal acid lipase mediates lipoprotein cholesteryl ester metabolism in a human vascular endothelial cell-fibroblast coculture system.

    PubMed Central

    Sando, G N; Ma, G P; Lindsley, K A; Wei, Y P

    1990-01-01

    We present results from studies of human cell culture models to support the premise that the extracellular transport of lysosomal acid lipase has a function in lipoprotein cholesteryl ester metabolism in vascular tissue. Vascular endothelial cells secreted a higher fraction of cellular acid lipase than did smooth muscle cells and fibroblasts. Acid lipase and lysosomal beta-hexosaminidase were secreted at approximately the same rate from the apical and basolateral surface of an endothelial cell monolayer. Stimulation of secretion with NH4Cl did not affect the polarity. We tested for the ability of secreted endothelial lipase to interact with connective tissue cells and influence lipoprotein cholesterol metabolism in a coculture system in which endothelial cells on a micropore filter were suspended above a monolayer of acid lipase-deficient (Wolman disease) fibroblasts. After 5-7 d, acid lipase activity in the fibroblasts reached 10%-20% of the level in normal cells; cholesteryl esters that had accumulated from growth in serum were cleared. Addition of mannose 6-phosphate to the coculture medium blocked acid lipase uptake and cholesterol clearance, indicating that lipase released from endothelial cells was packaged into fibroblast lysosomes by a phosphomannosyl receptor-mediated pathway. Supplementation of the coculture medium with serum was not required for lipase uptake and cholesteryl ester hydrolysis by the fibroblasts, but was necessary for cholesterol clearance. Results from our coculture model suggest that acid lipase may be transported from intact endothelium to cells in the lumen or the wall of a blood vessel. We postulate that delivery of acid hydrolases and lipoproteins to a common endocytic compartment may occur and have an impact on cellular lipoprotein processing. PMID:2150334

  6. Role of fatty acid transporters in epidermis

    PubMed Central

    Miner, Jeffrey H; Jahnsen, Frode

    2011-01-01

    Skin epidermis is an active site of lipid synthesis. The intercellular lipids of human stratum corneum (SC) are unique in composition and quite different from the lipids found in most biological membranes. The three major lipids in the SC are free fatty acids, cholesterol and ceramides. Fatty acids can be synthesized by keratinocytes de novo and, in addition, need to be taken up from the circulation. The latter process has been shown to be protein mediated, and several fatty acid transporters are expressed in skin. Recent studies of transgenic and knockout animal models for fatty acid transporters and the identification of fatty acid transport protein 4 (FATP4 or SLC27A4) mutations as causative for Ichthyosis Prematurity Syndrome highlight the vital roles of fatty acid transport and metabolism in skin homeostasis. This review provides an overview of our current understanding of the role of fatty acids and their transporters in cutaneous biology, including their involvement in epidermal barrier generation and skin inflammation. PMID:21695012

  7. Transportation Systems Evaluation

    NASA Technical Reports Server (NTRS)

    Fanning, M. L.; Michelson, R. A.

    1972-01-01

    A methodology for the analysis of transportation systems consisting of five major interacting elements is reported. The analysis begins with the causes of travel demand: geographic, economic, and demographic characteristics as well as attitudes toward travel. Through the analysis, the interaction of these factors with the physical and economic characteristics of the transportation system is determined. The result is an evaluation of the system from the point of view of both passenger and operator. The methodology is applicable to the intraurban transit systems as well as major airlines. Applications of the technique to analysis of a PRT system and a study of intraurban air travel are given. In the discussion several unique models or techniques are mentioned: i.e., passenger preference modeling, an integrated intraurban transit model, and a series of models to perform airline analysis.

  8. Quinone-amino acid conjugates targeting Leishmania amino acid transporters.

    PubMed

    Prati, Federica; Goldman-Pinkovich, Adele; Lizzi, Federica; Belluti, Federica; Koren, Roni; Zilberstein, Dan; Bolognesi, Maria Laura

    2014-01-01

    The aim of the present study was to investigate the feasibility of targeting Leishmania transporters via appropriately designed chemical probes. Leishmania donovani, the parasite that causes visceral leishmaniasis, is auxotrophic for arginine and lysine and has specific transporters (LdAAP3 and LdAAP7) to import these nutrients. Probes 1-15 were originated by conjugating cytotoxic quinone fragments (II and III) with amino acids (i.e. arginine and lysine) by means of an amide linkage. The toxicity of the synthesized conjugates against Leishmania extracellular (promastigotes) and intracellular (amastigotes) forms was investigated, as well their inhibition of the relevant amino acid transporters. We observed that some conjugates indeed displayed toxicity against the parasites; in particular, 7 was identified as the most potent derivative (at concentrations of 1 µg/mL and 2.5 µg/mL residual cell viability was reduced to 15% and 48% in promastigotes and amastigotes, respectively). Notably, 6, while retaining the cytotoxic activity of quinone II, displayed no toxicity against mammalian THP1 cells. Transport assays indicated that the novel conjugates inhibited transport activity of lysine, arginine and proline transporters. Furthermore, our analyses suggested that the toxic conjugates might be translocated by the transporters into the cells. The non-toxic probes that inhibited transport competed with the natural substrates for binding to the transporters without being translocated. Thus, it is likely that 6, by exploiting amino acid transporters, can selectively deliver its toxic effects to Leishmania cells. This work provides the first evidence that amino acid transporters of the human pathogen Leishmania might be modulated by small molecules, and warrants their further investigation from drug discovery and chemical biology perspectives. PMID:25254495

  9. Expression of heteromeric amino acid transporters along the murine intestine.

    PubMed

    Dave, Mital H; Schulz, Nicole; Zecevic, Marija; Wagner, Carsten A; Verrey, Francois

    2004-07-15

    Members of the new heterodimeric amino acid transporter family are composed of two subunits, a catalytic multitransmembrane spanning protein (light chain) and a type II glycoprotein (heavy chain). These transporters function as exchangers and thereby extend the transmembrane amino acid transport selectivity to specific amino acids. The heavy chain rBAT associates with the light chain b degrees (,+)AT to form a cystine and cationic amino acid transporter. The other heavy chain, 4F2hc, can interact with seven different light chains to form various transporters corresponding to systems L, y(+)L, asc or x(-)(c). The importance of some of these transporters in intestinal and renal (re)absorption of amino acids is highlighted by the fact that mutations in either the rBAT or b degrees (,+)AT subunit result in cystinuria whereas a defect in the y(+)-LAT1 light chain causes lysinuric protein intolerance. Here we investigated the localization of these transporters in intestine since both diseases are also characterized by altered intestinal amino acid absorption. Real time PCR showed organ-specific expression patterns for all transporter subunit mRNAs along the intestine and Western blotting confirmed these findings on the protein level. Immunohistochemistry demonstrated basolateral coexpression of 4F2hc, LAT2 and y(+)-LAT1 in stomach and small intestine, whereas rBAT and b degrees (,+)AT were found colocalizing on the apical side of small intestine epithelium. In stomach, 4F2hc and LAT2 were localized in H(+)/K(+)-ATPase-expressing parietal cells. The abundant expression of several members of the heterodimeric transporter family along the murine small intestine suggests their involvement in amino acids absorption. Furthermore, strong expression of rBAT, b degrees (,+)AT and y(+)-LAT1 in the small intestine explains the reduced intestinal absorption of some amino acid in patients with cystinuria or lysinuric protein intolerance.

  10. Transportation Anslysis Simulation System

    SciTech Connect

    2004-08-23

    TRANSIMS version 3.1 is an integrated set of analytical and simulation models and supporting databases. The system is designed to create a virtual metropolitan region with representation of each of the region’s individuals, their activities and the transportation infrastructure they use. TRANSIMS puts into practice a new, disaggregate approach to travel demand modeling using agent-based micro-simulation technology. TRANSIMS methodology creates a virtual metropolitan region with representation of the transportation infrastructure and the population, at the level of households and individual travelers. Trips a planned to satisfy the population’s activity pattems at the individual traveler level. TRANSIMS then simulates the movement of travelers and vehicles across the transportation network using multiple modes, including car, transit, bike and walk, on a second-by-second basis. Metropolitan planners must plan growth of their cities according to the stringent transportation system planning requirements of the Interniodal Surface Transportation Efficiency Act of 1991, the Clean Air Act Amendments of 1990 and other similar laws and regulations. These require each state and its metropotitan regions to work together to develop short and long term transportation improvement plans. The plans must (1) estimate the future transportation needs for travelers and goods movements, (2) evaluate ways to manage and reduce congestion, (3) examine the effectiveness of building new roads and transit systems, and (4) limit the environmental impact of the various strategies. The needed consistent and accurate transportation improvement plans require an analytical capability that properly accounts for travel demand, human behavior, traffic and transit operations, major investments, and environmental effects. Other existing planning tools use aggregated information and representative behavior to predict average response and average use of transportation facilities. They do not account

  11. Transportation Anslysis Simulation System

    2004-08-23

    TRANSIMS version 3.1 is an integrated set of analytical and simulation models and supporting databases. The system is designed to create a virtual metropolitan region with representation of each of the region’s individuals, their activities and the transportation infrastructure they use. TRANSIMS puts into practice a new, disaggregate approach to travel demand modeling using agent-based micro-simulation technology. TRANSIMS methodology creates a virtual metropolitan region with representation of the transportation infrastructure and the population, at themore » level of households and individual travelers. Trips a planned to satisfy the population’s activity pattems at the individual traveler level. TRANSIMS then simulates the movement of travelers and vehicles across the transportation network using multiple modes, including car, transit, bike and walk, on a second-by-second basis. Metropolitan planners must plan growth of their cities according to the stringent transportation system planning requirements of the Interniodal Surface Transportation Efficiency Act of 1991, the Clean Air Act Amendments of 1990 and other similar laws and regulations. These require each state and its metropotitan regions to work together to develop short and long term transportation improvement plans. The plans must (1) estimate the future transportation needs for travelers and goods movements, (2) evaluate ways to manage and reduce congestion, (3) examine the effectiveness of building new roads and transit systems, and (4) limit the environmental impact of the various strategies. The needed consistent and accurate transportation improvement plans require an analytical capability that properly accounts for travel demand, human behavior, traffic and transit operations, major investments, and environmental effects. Other existing planning tools use aggregated information and representative behavior to predict average response and average use of transportation facilities. They do not

  12. Acid rain and transported air pollutants

    SciTech Connect

    Not Available

    1985-01-01

    This book considers aspects of the air pollutant controversy. It discusses the following: the policy dilemma - including impact on terrestrial and aquatic eco-systems, effects on human health, diplomatic issues, and how control would benefit some industries and hurt others; scientific uncertainties about the extent and location of current damage, future damage, the origin of transported air pollutants, and the efficacy of current and proposed emissions control programs; how three major pollutants - sulfur dioxide, nitrous oxide, and reactive hydrocarbons - are distributed geographically; the effect of current legislation on acid rain and its distribution; how geographic and economic risks are dispersed throughout the United States; and other risks, such as potential damage to buildings and metals.

  13. A lunar transportation system

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Due to large amounts of oxygen required for space travel, a method of mining, transporting, and storing this oxygen in space would facilitate further space exploration. The following project deals specifically with the methods for transporting liquid oxygen from the lunar surface to the Lunar Orbit (LO) space station, and then to the Lower Earth Orbit (LEO) space station. Two vehicles were designed for operation between the LEO and LO space stations. The first of these vehicles is an aerobraked design vehicle. The Aerobrake Orbital Transfer Vehicle (OTV) is capable of transporting 5000 lbm of payload to LO while returning to LEO with 60,000 lbm of liquid oxygen, and thus meet mission requirements. The second vehicle can deliver 18,000 lbm of payload to LO and is capable of bringing 60,000 lbm of liquid oxygen back to LEO. A lunar landing vehicle was also designed for operation between LO and the established moon base. The use of an electromagnetic railgun as a method for launching the lunar lander was also investigated. The feasibility of the railgun is doubtful at this time. A system of spheres was also designed for proper storing and transporting of the liquid oxygen. The system assumes a safe means for transferring the liquid oxygen from tank to tank is operational. A sophisticated life support system was developed for both the OTV and the lunar lander. This system focuses on such factors as the vehicle environment, waste management, water requirements, food requirements, and oxygen requirements.

  14. Lunar transportation system

    NASA Technical Reports Server (NTRS)

    1993-01-01

    The University Space Research Association (USRA) requested the University of Minnesota Spacecraft Design Team to design a lunar transportation infrastructure. This task was a year long design effort culminating in a complete conceptual design and presentation at Johnson Space Center. The mission objective of the design group was to design a system of vehicles to bring a habitation module, cargo, and crew to the lunar surface from LEO and return either or both crew and cargo safely to LEO while emphasizing component commonality, reusability, and cost effectiveness. During the course of the design, the lunar transportation system (LTS) has taken on many forms. The final design of the system is composed of two vehicles, a lunar transfer vehicle (LTV) and a lunar excursion vehicle (LEV). The LTV serves as an efficient orbital transfer vehicle between the earth and the moon while the LEV carries crew and cargo to the lunar surface. Presented in the report are the mission analysis, systems layout, orbital mechanics, propulsion systems, structural and thermal analysis, and crew systems, avionics, and power systems for this lunar transportation concept.

  15. Heat transport system

    DOEpatents

    Pierce, Bill L.

    1978-01-01

    A heat transport system of small size which can be operated in any orientation consists of a coolant loop containing a vaporizable liquid as working fluid and includes in series a vaporizer, a condenser and two one-way valves and a pressurizer connected to the loop between the two valves. The pressurizer may be divided into two chambers by a flexible diaphragm, an inert gas in one chamber acting as a pneumatic spring for the system.

  16. Transportation Systems Center

    SciTech Connect

    Greer, G.S.

    1992-07-01

    The Transportation Systems Center at Sandia Laboratory performs research, development, and implementation of technologies that enhance the safe movement of people, goods, and information. Our focus is on systems engineering. However, we realize that to understand the puzzle, you must also understand the pieces. This brochure describes some of the activities currently underway at the Center and presents the breadth and depth of our capabilities. Please contact the noted, individuals for more, information.

  17. Role of the Intestinal Bile Acid Transporters in Bile Acid and Drug Disposition

    PubMed Central

    Dawson, Paul A.

    2011-01-01

    Membrane transporters expressed by the hepatocyte and enterocyte play critical roles in maintaining the enterohepatic circulation of bile acids, an effective recycling and conservation mechanism that largely restricts these potentially cytotoxic detergents to the intestinal and hepatobiliary compartments. In doing so, the hepatic and enterocyte transport systems ensure a continuous supply of bile acids to be used repeatedly during the digestion of multiple meals throughout the day. Absorption of bile acids from the intestinal lumen and export into the portal circulation is mediated by a series of transporters expressed on the enterocyte apical and basolateral membranes. The ileal apical sodium-dependent bile acid cotransporter (abbreviated ASBT; gene symbol, SLC10A2) is responsible for the initial uptake of bile acids across the enterocyte brush border membrane. The bile acids are then efficiently shuttled across the cell and exported across the basolateral membrane by the heteromeric Organic Solute Transporter, OSTα-OSTβ. This chapter briefly reviews the tissue expression, physiology, genetics, pathophysiology, and transport properties of the ASBT and OSTα-OSTα. In addition, the chapter discusses the relationship between the intestinal bile acid transporters and drug metabolism, including development of ASBT inhibitors as novel hypocholesterolemic or hepatoprotective agents, prodrug targeting of the ASBT to increase oral bioavailability, and involvement of the intestinal bile acid transporters in drug absorption and drug-drug interactions. PMID:21103970

  18. Primordial transport of sugars and amino acids via Schiff bases

    NASA Astrophysics Data System (ADS)

    Stillwell, William; Rau, Aruna

    1981-09-01

    Experimental support is given for a model concerning the origin of a primordial transport system. The model is based on the facilitated diffusion of amino acids stimulated by aliphatic aldehyde carriers and sugars stimulated by aliphatic amine carriers. The lipid-soluble diffusing species is the Schiff base. The possible role of this simple transport system in the origin of an early protocell is discussed.

  19. Intestinal transport and metabolism of bile acids

    PubMed Central

    Dawson, Paul A.; Karpen, Saul J.

    2015-01-01

    In addition to their classical roles as detergents to aid in the process of digestion, bile acids have been identified as important signaling molecules that function through various nuclear and G protein-coupled receptors to regulate a myriad of cellular and molecular functions across both metabolic and nonmetabolic pathways. Signaling via these pathways will vary depending on the tissue and the concentration and chemical structure of the bile acid species. Important determinants of the size and composition of the bile acid pool are their efficient enterohepatic recirculation, their host and microbial metabolism, and the homeostatic feedback mechanisms connecting hepatocytes, enterocytes, and the luminal microbiota. This review focuses on the mammalian intestine, discussing the physiology of bile acid transport, the metabolism of bile acids in the gut, and new developments in our understanding of how intestinal metabolism, particularly by the gut microbiota, affects bile acid signaling. PMID:25210150

  20. Role of amino acid transporters in amino acid sensing1234

    PubMed Central

    2014-01-01

    Amino acid (AA) transporters may act as sensors, as well as carriers, of tissue nutrient supplies. This review considers recent advances in our understanding of the AA-sensing functions of AA transporters in both epithelial and nonepithelial cells. These transporters mediate AA exchanges between extracellular and intracellular fluid compartments, delivering substrates to intracellular AA sensors. AA transporters on endosomal (eg, lysosomal) membranes may themselves function as intracellular AA sensors. AA transporters at the cell surface, particularly those for large neutral AAs such as leucine, interact functionally with intracellular nutrient-signaling pathways that regulate metabolism: for example, the mammalian target of rapamycin complex 1 (mTORC1) pathway, which promotes cell growth, and the general control non-derepressible (GCN) pathway, which is activated by AA starvation. Under some circumstances, upregulation of AA transporter expression [notably a leucine transporter, solute carrier 7A5 (SLC7A5)] is required to initiate AA-dependent activation of the mTORC1 pathway. Certain AA transporters may have dual receptor-transporter functions, operating as “transceptors” to sense extracellular (or intracellular) AA availability upstream of intracellular signaling pathways. New opportunities for nutritional therapy may include targeting of AA transporters (or mechanisms that upregulate their expression) to promote protein-anabolic signals for retention or recovery of lean tissue mass. PMID:24284439

  1. SUBSURFACE EMPLACEMENT TRANSPORTATION SYSTEM

    SciTech Connect

    T. Wilson; R. Novotny

    1999-11-22

    The objective of this analysis is to identify issues and criteria that apply to the design of the Subsurface Emplacement Transportation System (SET). The SET consists of the track used by the waste package handling equipment, the conductors and related equipment used to supply electrical power to that equipment, and the instrumentation and controls used to monitor and operate those track and power supply systems. Major considerations of this analysis include: (1) Operational life of the SET; (2) Geometric constraints on the track layout; (3) Operating loads on the track; (4) Environmentally induced loads on the track; (5) Power supply (electrification) requirements; and (6) Instrumentation and control requirements. This analysis will provide the basis for development of the system description document (SDD) for the SET. This analysis also defines the interfaces that need to be considered in the design of the SET. These interfaces include, but are not limited to, the following: (1) Waste handling building; (2) Monitored Geologic Repository (MGR) surface site layout; (3) Waste Emplacement System (WES); (4) Waste Retrieval System (WRS); (5) Ground Control System (GCS); (6) Ex-Container System (XCS); (7) Subsurface Electrical Distribution System (SED); (8) MGR Operations Monitoring and Control System (OMC); (9) Subsurface Facility System (SFS); (10) Subsurface Fire Protection System (SFR); (11) Performance Confirmation Emplacement Drift Monitoring System (PCM); and (12) Backfill Emplacement System (BES).

  2. Metabolism and transport of gamma-carboxyglutamic acid.

    PubMed

    Shah, D V; Tews, J K; Harper, A E; Suttie, J W

    1978-03-01

    gamma-Carboxyglutamic acid residues have beeh shown to be present in prothrombin, the other vitamin K-dependent clotting factors, and more recently in bone and kidney proteins. This amino acid is formed by a posttranslational vitamin K-dependent carboxylation of glutamyl residues in polypeptide precursors of these protens. It has now been demonstrated that this amino acid, either in the free or peptide-bound form, is not metabolically degraded by the rat, but is quantitatively excreted in the urine. In nephrectomized rats, the tissue concentration of intravenously administered gamma-carboxyglutamic acid is increased, but there is still no evidence of any oxidative metabolism of this amino acid. These amino acid is transported by kidney slices against a concentration gradient, but does not accumulate in liver, intestinal or brain tissues. Preliminary data suggest that gamma-carboxyglutamic acid may be concentrated by a carrier system different from that utilized by other amino acids. PMID:629998

  3. Mars Equipment Transport System

    NASA Technical Reports Server (NTRS)

    Sorrells, Cindy; Geiger, Michelle; Ohanlon, Sean; Pieloch, Stuart; Brogan, Nick

    1993-01-01

    Mechanical Engineering Senior Design Project 1 (ME4182) is a part of the NASA/University Advanced Design Program. Under this program, NASA allocates money and resources to students to be used in design work for a specified topic. The current topic is the exploration and colonization of Mars. The specific area in which we are to work is the transportation of the modules in which astronauts will live while on Mars. NASA is concerned about the weight of the module transferring system, as the shipping cost to Mars is quite expensive. NASA has specified that the weight of the system is to be minimized in order to reduce the shipping costs.

  4. Mars Equipment Transport System

    NASA Astrophysics Data System (ADS)

    Sorrells, Cindy; Geiger, Michelle; Ohanlon, Sean; Pieloch, Stuart; Brogan, Nick

    1993-12-01

    Mechanical Engineering Senior Design Project 1 (ME4182) is a part of the NASA/University Advanced Design Program. Under this program, NASA allocates money and resources to students to be used in design work for a specified topic. The current topic is the exploration and colonization of Mars. The specific area in which we are to work is the transportation of the modules in which astronauts will live while on Mars. NASA is concerned about the weight of the module transferring system, as the shipping cost to Mars is quite expensive. NASA has specified that the weight of the system is to be minimized in order to reduce the shipping costs.

  5. Space Transportation Systems Technologies

    NASA Technical Reports Server (NTRS)

    Laue, Jay H.

    2001-01-01

    This document is the final report by the Science Applications International Corporation (SAIC) on contracted support provided to the National Aeronautics and Space Administration (NASA) under Contract NAS8-99060, 'Space Transportation Systems Technologies'. This contract, initiated by NASA's Marshall Space Flight Center (MSFC) on February 8, 1999, was focused on space systems technologies that directly support NASA's space flight goals. It was awarded as a Cost-Plus-Incentive-Fee (CPIF) contract to SAIC, following a competitive procurement via NASA Research Announcement, NRA 8-21. This NRA was specifically focused on tasks related to Reusable Launch Vehicles (RLVs). Through Task Area 3 (TA-3), "Other Related Technology" of this NRA contract, SAIC extensively supported the Space Transportation Directorate of MSFC in effectively directing, integrating, and setting its mission, operations, and safety priorities for future RLV-focused space flight. Following an initially contracted Base Year (February 8, 1999 through September 30, 1999), two option years were added to the contract. These were Option Year 1 (October 1, 1999 through September 30, 2000) and Option Year 2 (October 1, 2000 through September 30, 2001). This report overviews SAIC's accomplishments for the Base Year, Option Year 1, and Option Year 2, and summarizes the support provided by SAIC to the Space Transportation Directorate, NASA/MSFC.

  6. Mars transportation system

    NASA Technical Reports Server (NTRS)

    Garrard, William; Vano, Andrew; Rutherford, Dave

    1992-01-01

    The University of Minnesota Advanced Space Design Program has developed a sample Mars exploration scenario. The purpose of the design project is to enhance NASA and university interaction, to provide fresh ideas to NASA, and to provide real world design problems to engineering students. The Mars Transportation System in this paper is designed to transport a crew of six astronauts to the Martian surface and return them to Low Earth Orbit (LEO) starting in the year 2016. The proposed vehicle features such advanced technologies as nuclear propulsion, nuclear power generation, and aerobraking. Three missions are planned. Orbital trajectories are of the conjunction class with an inbound Venus swingby providing a 60-day surface stay at Mars and an average total trip time of 520 days.

  7. Alternate transportation system

    NASA Technical Reports Server (NTRS)

    Zertuche, Tony; Mckinnie, James

    1988-01-01

    Three missions have been identified by NASA for a Space Shuttle-supplementing Alternate Transportation System (ATS) encompassing combinations of booster vehicles, crew modules, and service modules: (1) to achieve manned access to orbit for Space Station crew rotation every 90 days, (2) the lofting of a logistics module resupplying the Space Station every 180 days, and (3) the simultaneous launch of both crews and logistics to the Space Station. A reentry glider is considered, in conjunction with the Space Shuttle's unmanned cargo version and the Apollo manned capsule, as an important ATS element. The Titan IV/NUS is used as a booster.

  8. A TEM study of samples from acid mine drainage systems: metal-mineral association with implications for transport

    NASA Astrophysics Data System (ADS)

    Hochella, Michael F.; Moore, Johnnie N.; Golla, Ute; Putnis, Andrew

    1999-10-01

    Transmission electron microscopy (TEM), with energy dispersive X-ray (EDX) analysis and energy filtered transmission electron microscopy/electron energy loss spectroscopy (EFTEM/EELS), as well as powder X-ray diffraction (XRD) and scanning electron microscopy (SEM), have been used to study bed sediments from two acid mine drainage (AMD) sites in western Montana, USA. TEM and associated techniques, including sample preparation via epoxy impregnation and ultramicrotome sectioning, afford the opportunity to better interpret and understand complex water-rock interactions in these types of samples. For the sample taken from the first site (Mike Horse mine), ferrihydrite is the dominant phase, Si and Zn are the most abundant elements sorbed to ferrihydrite surfaces, and Pb is notably absent from ferrihydrite association. Three additional important metal-containing phases (gahnite, hydrohetaerolite, and plumbojarosite), that were not apparent in the powder XRD pattern because of their relatively low concentration, were identified in the TEM. The presence of these phases is important, because, for example, gahnite and plumbojarosite act as sinks for Zn and Pb, respectively. Therefore, the mobility of Pb from this part of the drainage system depends on the stability of plumbojarosite and the ability of ferrihydrite to sorb the released Pb. From thermodynamic data in the literature, we predict that Pb will be released by the dissolution of plumbojarosite above a pH of 4 to 5, but it will then be recaptured by ferrihydrite if the pH continues to rise to 5.5 and higher, irrespective of competition effects from other metals. Therefore, only a relatively narrow pH window exists in which Pb can escape this portion of the system as an aqueous species. For the sample taken from the other site included in this study (the Carbonate mine), jarosite and quartz are the dominant phases. Interestingly, however, the jarosites are both Pb-poor and Pb-enriched. In addition, TEM reveals the

  9. Portage transport of sulfanilamide and sulfanilic acid.

    PubMed

    Hwang, S Y; Berges, D A; Taggart, J J; Gilvarg, C

    1989-03-01

    Sulfanilic acid, in contrast to sulfanilamide, has poor in vitro antibacterial activity. Paradoxically, it has been shown to be a more effective inhibitor than sulfanilamide of dihydropteroic acid synthase. In order to circumvent the presumed permeability barrier to sulfanilic acid, advantage was taken of the technique of portage transport. Derivatives of the compound were prepared in which it was linked via its primary amino group to the alpha-carbon of glycine residues in di- and tripeptides. L-Alanyl-L-alanyl-L-2-[(4-sulfophenyl)amino]glycine proved to be 207 times more potent than sulfanilic acid and 8 times more active than either sulfanilamide or L-alanyl-L-alanyl-L-2-[[4-(aminosulfonyl)-phenyl]amino]glycine when tested against Escherichia coli. These findings confirm that the weak in vitro activity of sulfanilic acid is due to its limited ability to penetrate the bacterial membrane. They also emphasize the ability of portage transport to reveal therapeutic capability that had been attenuated by poor drug permeation.

  10. Effect of inhibitors of arachidonic acid metabolism on alpha-aminoisobutyric acid transport in human lymphocytes.

    PubMed

    Udey, M C; Parker, C W

    1982-02-01

    The role of arachidonic acid metabolism (or metabolites) in the modulation of alpha-aminoisobutyric acid transport in resting and concanavalin A-stimulated human peripheral blood lymphocytes was evaluated using previously characterized inhibitors of arachidonic acid metabolism. Nordihydroguairetic acid (a nonselective antioxidant), 5,8,11,14-eicosatetraynoic acid (an inhibitor of lipoxygenase and cyclooxygenase activities), indomethacin and acetylsalicylic acid (selective cyclooxygenase inhibitors), and 1-benzylimidazole, Ro-22-3581 and Ro-22-3582 (thromboxane synthetase inhibitors) proved to be potent inhibitors of amino acid transport activity in normal resting and lectin-activated lymphocytes at concentrations known to decrease thromboxane A2 production. The rank order of effectiveness of these various inhibitors compared favorably with their relative potencies as inhibitors of thromboxane B2 synthesis under the same conditions, as determined by radioimmunoassay. Inhibitory effects noted were not due to overt cytotoxicity and seemed to involve changes primarily in the Vmax and not the Km of the transport process. Drug-induced alterations in the magnitude of concanavalin A binding were not observed. These results suggest that the activity of amino acid transport systems can be influenced by certain arachidonic acid metabolites, probably thromboxanes, in both stimulated and unstimulated lymphocytes. In addition, these findings may provide a partial explanation for the observation that inhibitors of thromboxane formation prevent lymphocyte mitogenesis.

  11. Reactive solute transport in acidic streams

    USGS Publications Warehouse

    Broshears, R.E.

    1996-01-01

    Spatial and temporal profiles of Ph and concentrations of toxic metals in streams affected by acid mine drainage are the result of the interplay of physical and biogeochemical processes. This paper describes a reactive solute transport model that provides a physically and thermodynamically quantitative interpretation of these profiles. The model combines a transport module that includes advection-dispersion and transient storage with a geochemical speciation module based on MINTEQA2. Input to the model includes stream hydrologic properties derived from tracer-dilution experiments, headwater and lateral inflow concentrations analyzed in field samples, and a thermodynamic database. Simulations reproduced the general features of steady-state patterns of observed pH and concentrations of aluminum and sulfate in St. Kevin Gulch, an acid mine drainage stream near Leadville, Colorado. These patterns were altered temporarily by injection of sodium carbonate into the stream. A transient simulation reproduced the observed effects of the base injection.

  12. Abscisic acid transport in human erythrocytes.

    PubMed

    Vigliarolo, Tiziana; Guida, Lucrezia; Millo, Enrico; Fresia, Chiara; Turco, Emilia; De Flora, Antonio; Zocchi, Elena

    2015-05-22

    Abscisic acid (ABA) is a plant hormone involved in the response to environmental stress. Recently, ABA has been shown to be present and active also in mammals, where it stimulates the functional activity of innate immune cells, of mesenchymal and hemopoietic stem cells, and insulin-releasing pancreatic β-cells. LANCL2, the ABA receptor in mammalian cells, is a peripheral membrane protein that localizes at the intracellular side of the plasma membrane. Here we investigated the mechanism enabling ABA transport across the plasmamembrane of human red blood cells (RBC). Both influx and efflux of [(3)H]ABA occur across intact RBC, as detected by radiometric and chromatographic methods. ABA binds specifically to Band 3 (the RBC anion transporter), as determined by labeling of RBC membranes with biotinylated ABA. Proteoliposomes reconstituted with human purified Band 3 transport [(3)H]ABA and [(35)S]sulfate, and ABA transport is sensitive to the specific Band 3 inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. Once inside RBC, ABA stimulates ATP release through the LANCL2-mediated activation of adenylate cyclase. As ATP released from RBC is known to exert a vasodilator response, these results suggest a role for plasma ABA in the regulation of vascular tone.

  13. Transportation System Concept of Operations

    SciTech Connect

    N. Slater-Thompson

    2006-08-16

    The Nuclear Waste Policy Act of 1982 (NWPA), as amended, authorized the DOE to develop and manage a Federal system for the disposal of SNF and HLW. OCRWM was created to manage acceptance and disposal of SNF and HLW in a manner that protects public health, safety, and the environment; enhances national and energy security; and merits public confidence. This responsibility includes managing the transportation of SNF and HLW from origin sites to the Repository for disposal. The Transportation System Concept of Operations is the core high-level OCRWM document written to describe the Transportation System integrated design and present the vision, mission, and goals for Transportation System operations. By defining the functions, processes, and critical interfaces of this system early in the system development phase, programmatic risks are minimized, system costs are contained, and system operations are better managed, safer, and more secure. This document also facilitates discussions and understanding among parties responsible for the design, development, and operation of the Transportation System. Such understanding is important for the timely development of system requirements and identification of system interfaces. Information provided in the Transportation System Concept of Operations includes: the functions and key components of the Transportation System; system component interactions; flows of information within the system; the general operating sequences; and the internal and external factors affecting transportation operations. The Transportation System Concept of Operations reflects OCRWM's overall waste management system policies and mission objectives, and as such provides a description of the preferred state of system operation. The description of general Transportation System operating functions in the Transportation System Concept of Operations is the first step in the OCRWM systems engineering process, establishing the starting point for the lower level

  14. Substrate specificity of amino acid transport in sheep erythrocytes.

    PubMed Central

    Young, J D; Ellory, J C

    1977-01-01

    The specificity of amino acid transport in normal (high-glutathione) sheep erythrocytes was investigated by studying the interaction of various neutral and dibasic amino acids in both competition and exchange experiments. Apparent Ki values were obtained for amino acids as inhibitors of L-alanine influx. Amino acids previously found to be transported by high-glutathione cells at fast rates (L-cysteine, L-alpha-amino-n-butyrate) were the most effective inhibitors. D-Alanine and D-alpha-amino-n-butyrate were without effect. Of the remaining amino acids studied, only L-norvaline, L-valine, L-norleucine, L-serine and L-2,4-diamino-n-butyrate significantly inhibited L-alanine uptake. L-Alanine efflux from pre-loaded cells was markedly stimulated by extracellular L-alanine. Those amino acids that inhibited L-alanine influx also stimulated L-alanine efflux. In addition, D-alanine, D-alpha-amino-n-biutyrate, L-threonine, L-asparagine, L-alpha, beta-diaminoproprionate, L-ornithine, L-lysine and S-2-aminoethyl-L-cysteine also significantly stimulated L-alanine efflux. L-Lysine uptake was inhibited by L-alanine but not by D-alanine, and the inhibitory potency of L-alanine was not influenced by the replacement of Na+ in the incubation medium with choline. L-Lysine efflux from pre-loaded cells was stimulated by L-alanine but not by D-alanine. It is concluded that these cells possess a highly selective stero-specific amino acid-transport system. Although the optimum substrates are small neutral amino acids, this system also has a significant affinity for dibasic amino acids. PMID:849280

  15. The catalytic subunit of the system L1 amino acid transporter (slc7a5) facilitates nutrient signalling in mouse skeletal muscle.

    PubMed

    Poncet, Nadège; Mitchell, Fiona E; Ibrahim, Adel F M; McGuire, Victoria A; English, Grant; Arthur, J Simon C; Shi, Yun-Bo; Taylor, Peter M

    2014-01-01

    The System L1-type amino acid transporter mediates transport of large neutral amino acids (LNAA) in many mammalian cell-types. LNAA such as leucine are required for full activation of the mTOR-S6K signalling pathway promoting protein synthesis and cell growth. The SLC7A5 (LAT1) catalytic subunit of high-affinity System L1 functions as a glycoprotein-associated heterodimer with the multifunctional protein SLC3A2 (CD98). We generated a floxed Slc7a5 mouse strain which, when crossed with mice expressing Cre driven by a global promoter, produced Slc7a5 heterozygous knockout (Slc7a5+/-) animals with no overt phenotype, although homozygous global knockout of Slc7a5 was embryonically lethal. Muscle-specific (MCK Cre-mediated) Slc7a5 knockout (MS-Slc7a5-KO) mice were used to study the role of intracellular LNAA delivery by the SLC7A5 transporter for mTOR-S6K pathway activation in skeletal muscle. Activation of muscle mTOR-S6K (Thr389 phosphorylation) in vivo by intraperitoneal leucine injection was blunted in homozygous MS-Slc7a5-KO mice relative to wild-type animals. Dietary intake and growth rate were similar for MS-Slc7a5-KO mice and wild-type littermates fed for 10 weeks (to age 120 days) with diets containing 10%, 20% or 30% of protein. In MS-Slc7a5-KO mice, Leu and Ile concentrations in gastrocnemius muscle were reduced by ∼40% as dietary protein content was reduced from 30 to 10%. These changes were associated with >50% decrease in S6K Thr389 phosphorylation in muscles from MS-Slc7a5-KO mice, indicating reduced mTOR-S6K pathway activation, despite no significant differences in lean tissue mass between groups on the same diet. MS-Slc7a5-KO mice on 30% protein diet exhibited mild insulin resistance (e.g. reduced glucose clearance, larger gonadal adipose depots) relative to control animals. Thus, SLC7A5 modulates LNAA-dependent muscle mTOR-S6K signalling in mice, although it appears non-essential (or is sufficiently compensated by e.g. SLC7A8 (LAT2)) for maintenance

  16. Molecular basis of essential amino acid transport from studies of insect nutrient amino acid transporters of the SLC6 family (NAT-SLC6)

    PubMed Central

    Boudko, Dmitri Y.

    2012-01-01

    Two protein families that represent major components of essential amino acid transport in insects have been identified. They are annotated as the SLC6 and SLC7 families of transporters according to phylogenetic proximity to characterized amino acid transporters (HUGO nomenclature). Members of these families have been identified as important apical and basolateral parts of transepithelial essential amino acid absorption in the metazoan alimentary canal. Synergistically, they play critical physiological roles as essential substrate providers to diverse metabolic processes, including generic protein synthesis. This review briefly clarifies the requirements for amino acid transport and a variety of amino acid transport mechanisms, including the aforementioned families. Further it focuses on the large group of Nutrient Amino acid Transporters (NATs), which comprise a recently identified subfamily of the Neurotransmitter Sodium Symporter family (NSS or SLC6). The first insect NAT, cloned from the caterpillar gut, has a broad substrate spectrum similar to mammalian B0 transporters. Several new NAT-SLC6 members have been characterized in an effort to explore mechanisms for the essential amino acid absorption in model dipteran insects. The identification and functional characterization of new B0-like and narrow specificity transporters of essential amino acids in fruit fly and mosquitoes leads to a fundamentally important insight: that NATs evolved and act together as the integrated active core of a transport network that mediates active alimentary absorption and systemic distribution of essential amino acids. This role of NATs is projected from the most primitive prokaryotes to the most complex metazoan organisms, and represents an interesting platform for unraveling the molecular evolution of amino acid transport and modeling amino acid transport disorders. The comparative study of NATs elucidates important adaptive differences between essential amino acid transportomes

  17. Aerobic catabolism of phenylacetic acid in Pseudomonas putida U: biochemical characterization of a specific phenylacetic acid transport system and formal demonstration that phenylacetyl-coenzyme A is a catabolic intermediate.

    PubMed Central

    Schleissner, C; Olivera, E R; Fernández-Valverde, M; Luengo, J M

    1994-01-01

    The phenylacetic acid transport system (PATS) of Pseudomonas putida U was studied after this bacterium was cultured in a chemically defined medium containing phenylacetic acid (PA) as the sole carbon source. Kinetic measurement was carried out, in vivo, at 30 degrees C in 50 mM phosphate buffer (pH 7.0). Under these conditions, the uptake rate was linear for at least 3 min and the value of Km was 13 microM. The PATS is an active transport system that is strongly inhibited by 2,4-dinitrophenol, 4-nitrophenol (100%), KCN (97%), 2-nitrophenol (90%), or NaN3 (80%) added at a 1 mM final concentration (each). Glucose or D-lactate (10 mM each) increases the PATS in starved cells (140%), whereas arsenate (20 mM), NaF, or N,N'-dicyclohexylcarbodiimide (1 mM) did not cause any effect. Furthermore, the PATS is insensitive to osmotic shock. These data strongly suggest that the energy for the PATS is derived only from an electron transport system which causes an energy-rich membrane state. The thiol-containing compounds mercaptoethanol, glutathione, and dithiothreitol have no significant effect on the PATS, whereas thiol-modifying reagents such as N-ethylmaleimide and iodoacetate strongly inhibit uptake (100 and 93%, respectively). Molecular analogs of PA with a substitution (i) on the ring or (ii) on the acetyl moiety or those containing (iii) a different ring but keeping the acetyl moiety constant inhibit uptake to different extents. None of the compounds tested significantly increase the PA uptake rate except adipic acid, which greatly stimulates it (163%). The PATS is induced by PA and also, gratuitously, by some phenyl derivatives containing an even number of carbon atoms on the aliphatic moiety (4-phenyl-butyric, 6-phenylhexanoic, and 8-phenyloctanoic acids). However, similar compounds with an odd number of carbon atoms (benzoic, 3-phenylpropionic, 5-phenylvaleric, 7-phenylheptanoic, and 9-phenylnonanoic acids) as well as many other PA derivatives do not induce the system

  18. Vertebrate gastrointestinal fermentation: transport mechanisms for volatile fatty acids.

    PubMed

    Titus, E; Ahearn, G A

    1992-04-01

    Symbiotic microbial fermentation of plant polysaccharides can potentially provide significant levels of nutrients to host organisms in the form of volatile fatty acids (VFAs). Microbial fermentation can account for as much as 10% of maintenance energy requirements in carnivores and omnivores, and up to 80% in ruminant herbivores. In this review epithelial transport processes for the products of microbial fermentation are described in various mammalian and lower vertebrate species. Studies of transepithelial movement of VFA in vertebrate gastrointestinal systems have mostly been investigated in the mammals. In these it is widely held that the transmural movement of VFA is a concentration-dependent passive diffusion process whereby VFA is transported in the protonated form. A different model is described in this paper for carrier-mediated VFA transport, by way of anionic exchange with intracellular bicarbonate, in the intestine of a fermenting herbivorous teleost. These models for diffusive and carrier-mediated transport are compared and discussed from both physiological and experimental viewpoints.

  19. Boramino acid as a marker for amino acid transporters

    PubMed Central

    Liu, Zhibo; Chen, Haojun; Chen, Kai; Shao, Yihan; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan

    2015-01-01

    Amino acid transporters (AATs) are a series of integral channels for uphill cellular uptake of nutrients and neurotransmitters. Abnormal expression of AATs is often associated with cancer, addiction, and multiple mental diseases. Although methods to evaluate in vivo expression of AATs would be highly useful, efforts to develop them have been hampered by a lack of appropriate tracers. We describe a new class of AA mimics—boramino acids (BAAs)—that can serve as general imaging probes for AATs. The structure of a BAA is identical to that of the corresponding natural AA, except for an exotic replacement of the carboxylate with -BF3−. Cellular studies demonstrate strong AAT-mediated cell uptake, and animal studies show high tumor-specific accumulation, suggesting that BAAs hold great promise for the development of new imaging probes and smart AAT-targeting drugs. PMID:26601275

  20. Intestinal transport of sulfanilic acid in rats immunized with protein-sulfanilic acid conjugate.

    PubMed

    Yamamoto, A; Kawaratani, T; Kawashima, K; Hashida, M; Sezaki, H

    1990-07-01

    Intestinal transport of sulfanilic acid was examined by means of an in vitro everted sac technique in rats immunized with a bovine gamma-globulin-sulfanilic acid conjugate. At a low concentration of sulfanilic acid, the intestinal transport of sulfanilic acid was decreased in rats immunized with bovine gamma-globulin-sulfanilic acid conjugate. This phenomenon was dose dependent and antigen specific, since there was no difference in the transport of sulfanilic acid at a high concentration and of an unrelated hapten. These results suggested that parenteral immunization impaired not only the intestinal transport of macromolecular antigens, as previously shown, but also the transport of the low molecular weight hapten, sulfanilic acid.

  1. The structure of the gene ATRC1 coding for a cationic amino acid transport system in man: Molecular studies in lysinuric protein intolerance

    SciTech Connect

    Incerti, B.; Sebastio, G.; Parenti, G.

    1994-09-01

    The human cDNA (ATRC1) homologue of a murine gene encoding for a transporter specific for cationic amino acid (CAA) has been isolated. ATRC1 stimulates the uptake of CAA and shows the kinetic properties of system y+ when expressed in frog oocytes. To characterize the organization of the ATRC1 gene, a {lambda} phages genomic DNA library has been screened using an ATRC1 full length cDNA clone as a probe. Nine positive phages have been subcloned in plasmids and sequenced using cDNA specific primers to identify intron-exon junctions. The ATRC1 gene consists of 13 exons with an alternative first exon. Analysis of the intron/exon boundaries showed canonical sequences at the splice junction sites. ATRC1 expression pattern has been analyzed by RT-PCR. ATRC1 is expressed in adult fibroblasts and enterocytes, in fetal kidney, brain and heart, and in lymphoblastoid cell lines. The knowledge of structure and organization of ATRC1 can help in studying inborn errors of CAA transport. The best characterized among these diseases is Lysinuric Protein Intolerance (LPI) a multisystem disorder with impaired formation of urea and hyperammonemia after protein ingestion. Linkage analysis performed on 10 LPI patients from 9 Italian families using two intragenic RFLPs revealed 3 informative families and no recombinations. Using the CA-repeat microsatellite D12S120 (2 cM far from ATRC-1 locus) we found 7 informative families and 3 recombinational events. The sequence of the entire coding region of an LPI patient failed to show mutations. The data so far obtained do not seem to support the hypothesis that ATRC1 is the LPI gene.

  2. Amino acid transport in the intestine of the caiman.

    PubMed

    Coulson, R A; Hernandez, T

    1983-01-01

    Seventeen amino acids were fed singly to small caimans and the rates of their disappearance from the gut lumen, and of their appearance in intestinal mucosa, whole intestine, whole stomach, and plasma were determined. The results were compared with those in which massive amounts of protein were fed. When single amino acids were fed, only traces of arginine, ornithine, lysine, aspartate and asparagine were absorbed intact. Glycine, alanine and serine were absorbed rapidly reaching mucosal concentrations as high as 40 mM. The others were not concentrated as highly and most were absorbed by the mucosa more slowly than the glycine group. Protein feeding did not result in high amino acid concentrations in the mucosa. Whether amino acids were ingested as protein or in the free state, glycine, alanine and glutamine increased in the mucosa, suggesting these three incorporate nitrogen released from the others. It appeared that several transport systems operate if amino acids are given singly, and that a different more efficient transport system operates during protein digestion.

  3. Nitrate Transport System in Neurospora crassa

    PubMed Central

    Schloemer, Robert H.; Garrett, Reginald H.

    1974-01-01

    Nitrate uptake in Neurospora crassa has been investigated under various conditions of nitrogen nutrition by measuring the rate of disappearance of nitrate from the medium and by determining mycelial nitrate accumulation. The nitrate transport system is induced by either nitrate or nitrite, but is not present in mycelia grown on ammonia or Casamino Acids. The appearance of nitrate uptake activity is prevented by cycloheximide, puromycin, or 6-methyl purine. The induced nitrate transport system displays a Km for nitrate of 0.25 mM. Nitrate uptake is inhibited by metabolic poisons such as 2,4-dinitrophenol, cyanide, and antimycin A. Furthermore, mycelia can concentrate nitrate 50-fold. Ammonia and nitrite are non-competitive inhibitors with respect to nitrate, with Ki values of 0.13 and 0.17 mM, respectively. Ammonia does not repress the formation of the nitrate transport system. In contrast, the nitrate uptake system is repressed by Casamino Acids. All amino acids individually prevent nitrate accumulation, with the exception of methionine, glutamine, and alanine. The influence of nitrate reduction and the nitrate reductase protein on nitrate transport was investigated in wild-type Neurospora lacking a functional nitrate reductase and in nitrate non-utilizing mutants, nit-1, nit-2, and nit-3. These mycelia contain an inducible nitrate transport system which displays the same characteristics as those found in the wild-type mycelia having the functional nitrate reductase. These findings suggest that nitrate transport is not dependent upon nitrate reduction and that these two processes are separate events in the assimilation of nitrate. PMID:4274457

  4. Droplet transport system and methods

    NASA Technical Reports Server (NTRS)

    Neitzel, G. Paul (Inventor)

    2010-01-01

    Embodiments of droplet transport systems and methods are disclosed for levitating and transporting single or encapsulated droplets using thermocapillary convection. One method embodiment, among others comprises providing a droplet of a first liquid; and applying thermocapillary convection to the droplet to levitate and move the droplet.

  5. Amino Acid Transporters and Release of Hydrophobic Amino Acids in the Heterocyst-Forming Cyanobacterium Anabaena sp. Strain PCC 7120.

    PubMed

    Pernil, Rafael; Picossi, Silvia; Herrero, Antonia; Flores, Enrique; Mariscal, Vicente

    2015-04-23

    Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that can use inorganic compounds such as nitrate or ammonium as nitrogen sources. In the absence of combined nitrogen, it can fix N2 in differentiated cells called heterocysts. Anabaena also shows substantial activities of amino acid uptake, and three ABC-type transporters for amino acids have been previously characterized. Seven new loci encoding predicted amino acid transporters were identified in the Anabaena genomic sequence and inactivated. Two of them were involved in amino acid uptake. Locus alr2535-alr2541 encodes the elements of a hydrophobic amino acid ABC-type transporter that is mainly involved in the uptake of glycine. ORF all0342 encodes a putative transporter from the dicarboxylate/amino acid:cation symporter (DAACS) family whose inactivation resulted in an increased uptake of a broad range of amino acids. An assay to study amino acid release from Anabaena filaments to the external medium was set up. Net release of the alanine analogue α-aminoisobutyric acid (AIB) was observed when transport system N-I (a hydrophobic amino acid ABC-type transporter) was engaged in the uptake of a specific substrate. The rate of AIB release was directly proportional to the intracellular AIB concentration, suggesting leakage from the cells by diffusion.

  6. Amino Acid Transporters and Release of Hydrophobic Amino Acids in the Heterocyst-Forming Cyanobacterium Anabaena sp. Strain PCC 7120

    PubMed Central

    Pernil, Rafael; Picossi, Silvia; Herrero, Antonia; Flores, Enrique; Mariscal, Vicente

    2015-01-01

    Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that can use inorganic compounds such as nitrate or ammonium as nitrogen sources. In the absence of combined nitrogen, it can fix N2 in differentiated cells called heterocysts. Anabaena also shows substantial activities of amino acid uptake, and three ABC-type transporters for amino acids have been previously characterized. Seven new loci encoding predicted amino acid transporters were identified in the Anabaena genomic sequence and inactivated. Two of them were involved in amino acid uptake. Locus alr2535-alr2541 encodes the elements of a hydrophobic amino acid ABC-type transporter that is mainly involved in the uptake of glycine. ORF all0342 encodes a putative transporter from the dicarboxylate/amino acid:cation symporter (DAACS) family whose inactivation resulted in an increased uptake of a broad range of amino acids. An assay to study amino acid release from Anabaena filaments to the external medium was set up. Net release of the alanine analogue α-aminoisobutyric acid (AIB) was observed when transport system N-I (a hydrophobic amino acid ABC-type transporter) was engaged in the uptake of a specific substrate. The rate of AIB release was directly proportional to the intracellular AIB concentration, suggesting leakage from the cells by diffusion. PMID:25915115

  7. Amino Acid Transporters and Release of Hydrophobic Amino Acids in the Heterocyst-Forming Cyanobacterium Anabaena sp. Strain PCC 7120.

    PubMed

    Pernil, Rafael; Picossi, Silvia; Herrero, Antonia; Flores, Enrique; Mariscal, Vicente

    2015-01-01

    Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that can use inorganic compounds such as nitrate or ammonium as nitrogen sources. In the absence of combined nitrogen, it can fix N2 in differentiated cells called heterocysts. Anabaena also shows substantial activities of amino acid uptake, and three ABC-type transporters for amino acids have been previously characterized. Seven new loci encoding predicted amino acid transporters were identified in the Anabaena genomic sequence and inactivated. Two of them were involved in amino acid uptake. Locus alr2535-alr2541 encodes the elements of a hydrophobic amino acid ABC-type transporter that is mainly involved in the uptake of glycine. ORF all0342 encodes a putative transporter from the dicarboxylate/amino acid:cation symporter (DAACS) family whose inactivation resulted in an increased uptake of a broad range of amino acids. An assay to study amino acid release from Anabaena filaments to the external medium was set up. Net release of the alanine analogue α-aminoisobutyric acid (AIB) was observed when transport system N-I (a hydrophobic amino acid ABC-type transporter) was engaged in the uptake of a specific substrate. The rate of AIB release was directly proportional to the intracellular AIB concentration, suggesting leakage from the cells by diffusion. PMID:25915115

  8. Biological Electron Transport Systems

    PubMed Central

    Cowan, Dwaine O.; Pasternak, Gavril; Kaufman, Frank

    1970-01-01

    The solid-state electrical conductivities of a number of ferredoxin model compounds are reported. For one of these compounds, (KFeS2)n, an electron transfer rate for a 25 Å unit is shown to be at least 1 × 108 electrons sec-1. The rate becomes proportionally larger for smaller molecular units. This rapid rate is consistant with a short pipe model for electron transport between two reaction sites. Some of the factors leading to this rapid transfer rate are considered. PMID:5269247

  9. Intracellular boron accumulation in CHO-K1 cells using amino acid transport control.

    PubMed

    Sato, Eisuke; Yamamoto, Tetsuya; Shikano, Naoto; Ogura, Masato; Nakai, Kei; Yoshida, Fumiyo; Uemae, Yoji; Takada, Tomoya; Isobe, Tomonori; Matsumura, Akira

    2014-06-01

    BPA used in BNCT has a similar structure to some essential amino acids and is transported into tumor cells by amino acid transport systems. Previous study groups have tried various techniques of loading BPA to increase intracellular boron concentration. CHO-K1 cells demonstrate system L (LAT1) activity and are suitable for specifying the transport system of a neutral amino acid. In this study, we examined the intracellular accumulation of boron in CHO-K1 cells by amino acid transport control, which involves co-loading with L-type amino acid esters. Intracellular boron accumulation in CHO-K1 cells showed the greatest increased upon co-loading 1.0mM BPA, with 1.0mM l-Tyr-O-Et and incubating for 60min. This increase is caused by activation of a system L amino acid exchanger between BPA and l-Tyr. The amino acid esters are metabolized to amino acids by intracellular hydrolytic enzymes that increase the concentrations of intracellular amino acids and stimulate exchange transportation. We expect that this amino acid transport control will be useful for enhancing intracellular boron accumulation.

  10. Heat transport system

    DOEpatents

    Harkness, Samuel D.

    1982-01-01

    A falling bed of ceramic particles receives neutron irradiation from a neutron-producing plasma and thereby transports energy as heat from the plasma to a heat exchange location where the ceramic particles are cooled by a gas flow. The cooled ceramic particles are elevated to a location from which they may again pass by gravity through the region where they are exposed to neutron radiation. Ceramic particles of alumina, magnesia, silica and combinations of these materials are contemplated as high-temperature materials that will accept energy from neutron irradiation. Separate containers of material incorporating lithium are exposed to the neutron flux for the breeding of tritium that may subsequently be used in neutron-producing reactions. The falling bed of ceramic particles includes velocity partitioning between compartments near to the neutron-producing plasma and compartments away from the plasma to moderate the maximum temperature in the bed.

  11. Heat transport system

    DOEpatents

    Harkness, S.D.

    A falling bed of ceramic particles receives neutron irradiation from a neutron-producing plasma and thereby transports energy as heat from the plasma to a heat exchange location where the ceramic particles are cooled by a gas flow. The cooled ceramic particles are elevated to a location from which they may again pass by gravity through the region where they are exposed to neutron radiation. Ceramic particles of alumina, magnesia, silica and combinations of these materials are contemplated as high-temperature materials that will accept energy from neutron irradiation. Separate containers of material incorporating lithium are exposed to the neutron flux for the breeding of tritium that may subsequently be used in neutron-producing reactions. The falling bed of ceramic particles includes velocity partitioning between compartments near to the neutron-producing plasma and compartments away from the plasma to moderate the maximum temperature in the bed.

  12. Advanced Transport Operating Systems Program

    NASA Technical Reports Server (NTRS)

    White, John J.

    1990-01-01

    NASA-Langley's Advanced Transport Operating Systems Program employs a heavily instrumented, B 737-100 as its Transport Systems Research Vehicle (TRSV). The TRSV has been used during the demonstration trials of the Time Reference Scanning Beam Microwave Landing System (TRSB MLS), the '4D flight-management' concept, ATC data links, and airborne windshear sensors. The credibility obtainable from successful flight test experiments is often a critical factor in the granting of substantial commitments for commercial implementation by the FAA and industry. In the case of the TRSB MLS, flight test demonstrations were decisive to its selection as the standard landing system by the ICAO.

  13. Tether Transportation System Study

    NASA Technical Reports Server (NTRS)

    Bangham, M. E.; Lorenzini, E.; Vestal, L.

    1998-01-01

    The projected traffic to geostationary earth orbit (GEO) is expected to increase over the next few decades. At the same time, the cost of delivering payloads from the Earth's surface to low earth orbit (LEO) is projected to decrease, thanks in part to the Reusable Launch Vehicle (RLV). A comparable reduction in the cost of delivering payloads from LEO to GEO is sought. The use of in-space tethers, eliminating the requirement for traditional chemical upper stages and thereby reducing the launch mass, has been identified as such an alternative. Spinning tethers are excellent kinetic energy storage devices for providing the large delta vee's required for LEO to GEO transfer. A single-stage system for transferring payloads from LEO to GEO was proposed some years ago. The study results presented here contain the first detailed analyses of this proposal, its extension to a two-stage system, and the likely implementation of the operational system.

  14. Novel Lactate Transporters from Carboxylic Acid-Producing Rhizopus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fungus Rhizopus is frequently used for fermentative production of lactic acid, but little is known about the mechanisms or proteins for transporting this carboxylic acid. Since transport of the lactate anion across the plasma membrane is critical to prevent acidification of the cytoplasm, we ev...

  15. Identification and characterization of an amino acid transporter expressed differentially in liver

    PubMed Central

    Gu, Sumin; Roderick, Hywel Llewelyn; Camacho, Patricia; Jiang, Jean X.

    2000-01-01

    Cellular metabolic needs are fulfilled by transport of amino acids across the plasma membrane by means of specialized transporter proteins. Although many of the classical amino acid transporters have been characterized functionally, less than half of these proteins have been cloned. In this report, we identify and characterize a cDNA encoding a plasma membrane amino acid transporter. The deduced amino acid sequence is 505 residues and is highly hydrophobic with the likely predicted structure of 9 transmembrane domains, which putatively place the amino terminus in the cytoplasm and the carboxy terminus on the cell surface. Expression of the cRNA in Xenopus laevis oocytes revealed strong transport activities specific for histidine and glutamine. This protein is a Na+- and pH-dependent transporter and tolerates substitution of Na+ by Li+. Furthermore, this transporter is not an obligatory exchanger because efflux occurs in the absence of influx. This transporter is expressed predominantly in the liver, although it is also present in the kidney, brain, and heart. In the liver, it is located in the plasma membrane of hepatocytes, and the strongest expression was detected in those adjacent to the central vein, gradually decreasing towards the portal tract. Because this protein displays functional similarities to the N-system amino acid transport, we have termed it mNAT, for murine N-system amino acid transporter. This is the first transporter gene identified within the N-system, one of the major amino acid transport systems in the body. The expression pattern displayed by mNAT suggests a potential role in hepatocyte physiology. PMID:10716701

  16. Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4).

    PubMed

    Ziegler, Kerstin; Kerimi, Asimina; Poquet, Laure; Williamson, Gary

    2016-06-01

    Ferulic acid is released by microbial hydrolysis in the colon, where butyric acid, a major by-product of fermentation, constitutes the main energy source for colonic enterocytes. We investigated how varying concentrations of this short chain fatty acid may influence the absorption of the phenolic acid. Chronic treatment of Caco-2 cells with butyric acid resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion. Short term incubation with butyric acid only led to upregulation of MCT4 while both conditions increased transepithelial transport of ferulic acid in the apical to basolateral, but not basolateral to apical, direction. Chronic treatment also elevated intracellular concentrations of ferulic acid, which in turn gave rise to increased concentrations of ferulic acid metabolites. Immunofluorescence staining of cells revealed uniform distribution of MCT1 protein in the cell membrane, whereas MCT4 was only detected in the lateral plasma membrane sections of Caco-2 cells. We therefore propose that MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid. PMID:26854723

  17. Transport Systems in Halophilic Fungi.

    PubMed

    Plemenitaš, Ana; Konte, Tilen; Gostinčar, Cene; Cimerman, Nina Gunde

    2016-01-01

    Fungi that tolerate very high environmental NaCl concentrations are good model systems to study mechanisms that enable them to endure osmotic and salinity stress. The whole genome sequences of six such fungal species have been analysed: Hortaea werneckii, Wallemia ichthyophaga and four Aureobasidium spp.: A. pullulans, A. subglaciale, A. melanogenum and A. namibiae. These fungi show different levels of halotolerance, with the presence of numerous membrane transport systems uncovered here that are believed to maintain physiological intracellular concentrations of alkali metal cations. Despite some differences, the intracellular cation contents of H. werneckii, A. pullulans and W. ichthyophaga remain low even under extreme extracellular salinities, which suggests that these species have efficient cation transport systems. We speculate that cation transporters prevent intracellular accumulation of Na(+), and thus avoid the toxic effects that such Na(+) accumulation would have, while also maintaining the high K(+)/Na(+) ratio that is required for the full functioning of the cell - another crucial task in high-Na(+) environments. This chapter primarily summarises the cation transport systems of these selected fungi, and it also describes other membrane transporters that might be involved in their mechanisms of halotolerance.

  18. Ascorbic acid transport and accumulation in human neutrophils

    SciTech Connect

    Washko, P.; Rotrosen, D.; Levine, M. )

    1989-11-15

    The transport, accumulation, and distribution of ascorbic acid were investigated in isolated human neutrophils utilizing a new ascorbic acid assay, which combined the techniques of high performance liquid chromatography and coulometric electrochemical detection. Freshly isolated human neutrophils contained 1.0-1.4 mM ascorbic acid, which was localized greater than or equal to 94% to the cytosol, was not protein bound, and was present only as ascorbic acid and not as dehydroascorbic acid. Upon addition of ascorbic acid to the extracellular medium in physiologic amounts, ascorbic acid was accumulated in neutrophils in millimolar concentrations. Accumulation was mediated by a high affinity and a low affinity transporter; both transporters were responsible for maintenance of concentration gradients as large as 50-fold. The high affinity transporter had an apparent Km of 2-5 microns by Lineweaver-Burk and Eadie-Hofstee analyses, and the low affinity transporter had an apparent Km of 6-7 mM by similar analyses. Each transporter was saturable and temperature dependent. In normal human blood the high affinity transporter should be saturated, whereas the low affinity transporter should be in its linear phase of uptake.

  19. Differential regulation of placental amino acid transport by saturated and unsaturated fatty acids.

    PubMed

    Lager, Susanne; Jansson, Thomas; Powell, Theresa L

    2014-10-15

    Fatty acids are critical for normal fetal development but may also influence placental function. We have previously reported that oleic acid (OA) stimulates amino acid transport in primary human trophoblasts (PHTs). In other tissues, saturated and unsaturated fatty acids have distinct effects on cellular signaling, for instance, palmitic acid (PA) but not OA reduces IκBα expression. We hypothesized that saturated and unsaturated fatty acids differentially affect trophoblast amino acid transport and cellular signaling. To test this hypothesis, PHTs were cultured in docosahexaenoic acid (DHA; 50 μM), OA (100 μM), or PA (100 μM). DHA and OA were also combined to test whether DHA could counteract the OA stimulatory effect on amino acid transport. The effects of fatty acids were compared against a vehicle control. Amino acid transport was measured by isotope-labeled tracers. Activation of inflammatory-related signaling pathways and the mechanistic target of rapamycin (mTOR) pathway were determined by Western blot analysis. Exposure of PHTs to DHA for 24 h reduced amino acid transport and phosphorylation of p38 MAPK, STAT3, mTOR, eukaryotic initiation factor 4E-binding protein 1, and ribosomal protein (rp)S6. In contrast, OA increased amino acid transport and phosphorylation of ERK, mTOR, S6 kinase 1, and rpS6. The combination of DHA with OA increased amino acid transport and rpS6 phosphorylation. PA did not affect amino acid transport but reduced IκBα expression. In conclusion, these fatty acids differentially regulated placental amino acid transport and cellular signaling. Taken together, these findings suggest that dietary fatty acids could alter the intrauterine environment by modifying placental function, thereby having long-lasting effects on the developing fetus.

  20. Earthquake damage to transportation systems

    USGS Publications Warehouse

    McCullough, Heather

    1994-01-01

    Earthquakes represent one of the most destructive natural hazards known to man. A large magnitude earthquake near a populated area can affect residents over thousands of square kilometers and cause billions of dollars in property damage. Such an event can kill or injure thousands of residents and disrupt the socioeconomic environment for months, sometimes years. A serious result of a large-magnitude earthquake is the disruption of transportation systems, which limits post-disaster emergency response. Movement of emergency vehicles, such as police cars, fire trucks and ambulances, is often severely restricted. Damage to transportation systems is categorized below by cause including: ground failure, faulting, vibration damage, and tsunamis.

  1. Surveillance systems for intermodal transportation

    NASA Astrophysics Data System (ADS)

    Jakovlev, Sergej; Voznak, Miroslav; Andziulis, Arunas

    2015-05-01

    Intermodal container monitoring is considered a major security issue in many major logistic companies and countries worldwide. Current representation of the problem, we face today, originated in 2002, right after the 9/11 attacks. Then, a new worldwide Container Security Initiative (CSI, 2002) was considered that shaped the perception of the transportation operations. Now more than 80 larger ports all over the world contribute to its further development and integration into everyday transportation operations and improve the regulations for the developing regions. Although, these new improvements allow us to feel safer and secure, constant management of transportation operations has become a very difficult problem for conventional data analysis methods and information systems. The paper deals with a proposal of a whole new concept for the improvement of the Containers Security Initiative (CSI) by virtually connecting safety, security processes and systems. A conceptual middleware approach with deployable intelligent agent modules is proposed to be used with possible scenarios and a testbed is used to test the solution. Middleware examples are visually programmed using National Instruments LabView software packages and Wireless sensor network hardware modules. An experimental software is used to evaluate he solution. This research is a contribution to the intermodal transportation and is intended to be used as a means or the development of intelligent transport systems.

  2. Expression of apical Na(+)-L-glutamine co-transport activity, B(0)-system neutral amino acid co-transporter (B(0)AT1) and angiotensin-converting enzyme 2 along the jejunal crypt-villus axis in young pigs fed a liquid formula

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gut apical amino acid (AA) transport activity is high at birth and during suckling, thus being essential to maintain luminal nutrient-dependent mucosal growth through providing AA as essential metabolic fuel, substrates and nutrient stimuli for cellular growth. Because system-B(0) Na(+)-neutral AA c...

  3. Alaska Natural Gas Transportation System

    SciTech Connect

    Jones, V.T.

    1984-04-27

    The proven reserves of natural gas in Prudhoe Bay remain the single largest block of reserves under US control. The sponsors of the Alaska Natural Gas Transportation System, including The Williams Companies, remain convinced that Alaskan gas will be increasingly important to meet future needs here in the lower 48 states. Both Canada and the US will increasingly have to turn to more costly supplies of gas as the closer, traditional areas of gas supply are exhausted. A principal motivation for Canada's participation in the ANGTS was the prospect of a jointly sponsored pipeline through Canada which would facilitate bringing frontier gas to market - through the so-called Dempster lateral. The high cost of transportation systems in the Artic necessitates pipelines with large capacities in order to minimize the cost of transportation per unit of gas delivered. It is clear that Canada still strongly supports the ANGTS project as a means of opening up the frontier resources of both Alaska and Canada.

  4. Optimal concentrations in transport systems

    PubMed Central

    Jensen, Kaare H.; Kim, Wonjung; Holbrook, N. Michele; Bush, John W. M.

    2013-01-01

    Many biological and man-made systems rely on transport systems for the distribution of material, for example matter and energy. Material transfer in these systems is determined by the flow rate and the concentration of material. While the most concentrated solutions offer the greatest potential in terms of material transfer, impedance typically increases with concentration, thus making them the most difficult to transport. We develop a general framework for describing systems for which impedance increases with concentration, and consider material flow in four different natural systems: blood flow in vertebrates, sugar transport in vascular plants and two modes of nectar drinking in birds and insects. The model provides a simple method for determining the optimum concentration copt in these systems. The model further suggests that the impedance at the optimum concentration μopt may be expressed in terms of the impedance of the pure (c = 0) carrier medium μ0 as μopt∼2αμ0, where the power α is prescribed by the specific flow constraints, for example constant pressure for blood flow (α = 1) or constant work rate for certain nectar-drinking insects (α = 6). Comparing the model predictions with experimental data from more than 100 animal and plant species, we find that the simple model rationalizes the observed concentrations and impedances. The model provides a universal framework for studying flows impeded by concentration, and yields insight into optimization in engineered systems, such as traffic flow. PMID:23594815

  5. Lunar articulated remote transportation system

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The students of the Florida A&M/Florida State University College of Engineering continued their design from 1988 to 1989 on a first generation lunar transportation vehicle for use on the surface of the Moon between the years 2010 and 2020. Attention is focused on specific design details on all components of the Lunar Articulated Remote Transportation System (Lunar ARTS). The Lunar ARTS will be a three-cart, six-wheeled articulated vehicle. Its purpose will be the transportation of astronauts and/or materials for excavation purposes at a short distance from the base (37.5 km). The power system includes fuel cells for both the primary system and the back-up system. The vehicle has the option of being operated in a manned or unmanned mode. The unmanned mode includes stereo imaging with signal processing for navigation. For manned missions the display console is a digital readout displayed on the inside of the astronaut's helmet. A microprocessor is also on board the vehicle. Other components of the vehicle include a double wishbone/flexible hemispherical wheel suspension; chassis; a steering system; motors; seat retraints; heat rejection systems; solar flare protection; dust protection; and meteoroid protection. A one-quarter scale dynamic model has been built to study the dynamic behavior of the vehicle. The dynamic model closely captures the mechanical and electrical details of the total design.

  6. Lunar articulated remote transportation system

    NASA Technical Reports Server (NTRS)

    Beech, Geoffrey; Conley, Gerald; Diaz, Claudine; Dimella, Timothy; Dodson, Pete; Hykin, Jeff; Richards, Byron; Richardson, Kroy; Shetzer, Christie; Vandyke, Melissa

    1990-01-01

    A first generation lunar transportation vehicle was designed for use on the surface of the Moon between the years 2010 and 2020. Attention is focussed on specific design details on all components of the Lunar Articulated Remote Transportation System (Lunar ARTS). The Lunar ARTS will be a three cart, six-wheeled articulated vehicle. It's purpose will be for the transportation of astronauts and/or materials for excavation purposes at a short distance from the base (37.5 kilometers). The power system includes fuel cells for both the primary system and the back-up system. The vehicle has the option of being operated in a manned or unmanned mode. The unmanned mode includes stereo imaging with signal processing for navigation. For manned missions the display console is a digital readout displayed on the inside of the asronaut's helmet. A microprocessor is also on board the vehicle. Other components of the vehicle include: a double wishbone/flexible hemispherical wheel suspension; chassis; a steering system; motors; seat restraints, heat rejection systems; solar flare protection; dust protection; and meteoroid protection. A one-quarter scale dynamic model was built to study the dynamic behavior of the vehicle. The dynamic model closely captures the mechanical and electrical details of the total design.

  7. Integrated Intermodal Passenger Transportation System

    NASA Technical Reports Server (NTRS)

    Klock, Ryan; Owens, David; Schwartz, Henry; Plencner, Robert

    2012-01-01

    Modern transportation consists of many unique modes of travel. Each of these modes and their respective industries has evolved independently over time, forming a largely incoherent and inefficient overall transportation system. Travelers today are forced to spend unnecessary time and efforts planning a trip through varying modes of travel each with their own scheduling, pricing, and services; causing many travelers to simply rely on their relatively inefficient and expensive personal automobile. This paper presents a demonstration program system to not only collect and format many different sources of trip planning information, but also combine these independent modes of travel in order to form optimal routes and itineraries of travel. The results of this system show a mean decrease in inter-city travel time of 10 percent and a 25 percent reduction in carbon dioxide emissions over personal automobiles. Additionally, a 55 percent reduction in carbon dioxide emissions is observed for intra-city travel. A conclusion is that current resources are available, if somewhat hidden, to drastically improve point to point transportation in terms of time spent traveling, the cost of travel, and the ecological impact of a trip. Finally, future concepts are considered which could dramatically improve the interoperability and efficiency of the transportation infrastructure.

  8. Amino acid transporters: roles in amino acid sensing and signalling in animal cells.

    PubMed Central

    Hyde, Russell; Taylor, Peter M; Hundal, Harinder S

    2003-01-01

    Amino acid availability regulates cellular physiology by modulating gene expression and signal transduction pathways. However, although the signalling intermediates between nutrient availability and altered gene expression have become increasingly well documented, how eukaryotic cells sense the presence of either a nutritionally rich or deprived medium is still uncertain. From recent studies it appears that the intracellular amino acid pool size is particularly important in regulating translational effectors, thus, regulated transport of amino acids across the plasma membrane represents a means by which the cellular response to amino acids could be controlled. Furthermore, evidence from studies with transportable amino acid analogues has demonstrated that flux through amino acid transporters may act as an initiator of nutritional signalling. This evidence, coupled with the substrate selectivity and sensitivity to nutrient availability classically associated with amino acid transporters, plus the recent discovery of transporter-associated signalling proteins, demonstrates a potential role for nutrient transporters as initiators of cellular nutrient signalling. Here, we review the evidence supporting the idea that distinct amino acid "receptors" function to detect and transmit certain nutrient stimuli in higher eukaryotes. In particular, we focus on the role that amino acid transporters may play in the sensing of amino acid levels, both directly as initiators of nutrient signalling and indirectly as regulators of external amino acid access to intracellular receptor/signalling mechanisms. PMID:12879880

  9. Identification and application of keto acids transporters in Yarrowia lipolytica.

    PubMed

    Guo, Hongwei; Liu, Peiran; Madzak, Catherine; Du, Guocheng; Zhou, Jingwen; Chen, Jian

    2015-01-30

    Production of organic acids by microorganisms is of great importance for obtaining building-block chemicals from sustainable biomass. Extracellular accumulation of organic acids involved a series of transporters, which play important roles in the accumulation of specific organic acid while lack of systematic demonstration in eukaryotic microorganisms. To circumvent accumulation of by-product, efforts have being orchestrated to carboxylate transport mechanism for potential clue in Yarrowia lipolytica WSH-Z06. Six endogenous putative transporter genes, YALI0B19470g, YALI0C15488g, YALI0C21406g, YALI0D24607g, YALI0D20108g and YALI0E32901g, were identified. Transport characteristics and substrate specificities were further investigated using a carboxylate-transport-deficient Saccharomyces cerevisiae strain. These transporters were expressed in Y. lipolytica WSH-Z06 to assess their roles in regulating extracellular keto acids accumulation. In a Y. lipolytica T1 line over expressing YALI0B19470g, α-ketoglutarate accumulated to 46.7 g·L(-1), whereas the concentration of pyruvate decreased to 12.3 g·L(-1). Systematic identification of these keto acids transporters would provide clues to further improve the accumulation of specific organic acids with higher efficiency in eukaryotic microorganisms.

  10. Identification and application of keto acids transporters in Yarrowia lipolytica

    PubMed Central

    Guo, Hongwei; Liu, Peiran; Madzak, Catherine; Du, Guocheng; Zhou, Jingwen; Chen, Jian

    2015-01-01

    Production of organic acids by microorganisms is of great importance for obtaining building-block chemicals from sustainable biomass. Extracellular accumulation of organic acids involved a series of transporters, which play important roles in the accumulation of specific organic acid while lack of systematic demonstration in eukaryotic microorganisms. To circumvent accumulation of by-product, efforts have being orchestrated to carboxylate transport mechanism for potential clue in Yarrowia lipolytica WSH-Z06. Six endogenous putative transporter genes, YALI0B19470g, YALI0C15488g, YALI0C21406g, YALI0D24607g, YALI0D20108g and YALI0E32901g, were identified. Transport characteristics and substrate specificities were further investigated using a carboxylate-transport-deficient Saccharomyces cerevisiae strain. These transporters were expressed in Y. lipolytica WSH-Z06 to assess their roles in regulating extracellular keto acids accumulation. In a Y. lipolytica T1 line over expressing YALI0B19470g, α-ketoglutarate accumulated to 46.7 g·L−1, whereas the concentration of pyruvate decreased to 12.3 g·L−1. Systematic identification of these keto acids transporters would provide clues to further improve the accumulation of specific organic acids with higher efficiency in eukaryotic microorganisms. PMID:25633653

  11. Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport.

    PubMed

    Boeuf, Philippe; Aitken, Elizabeth H; Chandrasiri, Upeksha; Chua, Caroline Lin Lin; McInerney, Bernie; McQuade, Leon; Duffy, Michael; Molyneux, Malcolm; Brown, Graham; Glazier, Jocelyn; Rogerson, Stephen J

    2013-02-01

    Placental malaria (PM) can lead to poor neonatal outcomes, including low birthweight due to fetal growth restriction (FGR), especially when associated with local inflammation (intervillositis or IV). The pathogenesis of PM-associated FGR is largely unknown, but in idiopathic FGR, impaired transplacental amino acid transport, especially through the system A group of amino acid transporters, has been implicated. We hypothesized that PM-associated FGR could result from impairment of transplacental amino acid transport triggered by IV. In a cohort of Malawian women and their infants, the expression and activity of system A (measured by Na⁺-dependent ¹⁴C-MeAIB uptake) were reduced in PM, especially when associated with IV, compared to uninfected placentas. In an in vitro model of PM with IV, placental cells exposed to monocyte/infected erythrocytes conditioned medium showed decreased system A activity. Amino acid concentrations analyzed by reversed phase ultra performance liquid chromatography in paired maternal and cord plasmas revealed specific alterations of amino acid transport by PM, especially with IV. Overall, our data suggest that the fetoplacental unit responds to PM by altering its placental amino acid transport to maintain adequate fetal growth. However, IV more profoundly compromises placental amino acid transport function, leading to FGR. Our study offers the first pathogenetic explanation for FGR in PM.

  12. Carboxylic Acids Plasma Membrane Transporters in Saccharomyces cerevisiae.

    PubMed

    Casal, Margarida; Queirós, Odília; Talaia, Gabriel; Ribas, David; Paiva, Sandra

    2016-01-01

    This chapter covers the functionally characterized plasma membrane carboxylic acids transporters Jen1, Ady2, Fps1 and Pdr12 in the yeast Saccharomyces cerevisiae, addressing also their homologues in other microorganisms, as filamentous fungi and bacteria. Carboxylic acids can either be transported into the cells, to be used as nutrients, or extruded in response to acid stress conditions. The secondary active transporters Jen1 and Ady2 can mediate the uptake of the anionic form of these substrates by a H(+)-symport mechanism. The undissociated form of carboxylic acids is lipid-soluble, crossing the plasma membrane by simple diffusion. Furthermore, acetic acid can also be transported by facilitated diffusion via Fps1 channel. At the cytoplasmic physiological pH, the anionic form of the acid prevails and it can be exported by the Pdr12 pump. This review will highlight the mechanisms involving carboxylic acids transporters, and the way they operate according to the yeast cell response to environmental changes, as carbon source availability, extracellular pH and acid stress conditions.

  13. Effects of dibutyryl cyclic AMP and papaverine on intrahepatocytic bile acid transport. Role of vesicle transport.

    PubMed

    Hoshino, M; Ohiwa, T; Hayakawa, T; Kamiya, Y; Tanaka, A; Hirano, A; Kumai, T; Katagiri, K; Miyaji, M; Takeuchi, T

    1993-09-01

    The secondary messenger cyclic AMP plays an important role in regulating biliary excretory function by stimulating the transcytotic vesicle transport system, whereas papaverine exerts an inhibitory effect on this system. We therefore investigated their effects on bile acid-induced cytotoxicity and intrahepatocytic content of bile acid in primary cultured rat hepatocytes. Simultaneous addition of 1 mM dibutyryl cyclic AMP (DBcAMP), an analogue of cAMP, with 1 mM taurochenodeoxycholic acid (TCDCA) significantly decreased the release of lactate dehydrogenase (LDH) as compared with the case with 1 mM TCDCA alone (7.1 +/- 0.13% of total versus 10.7 +/- 0.3%). In contrast, 0.1 mM papaverine approximately doubled the amount of LDH (22.0 +/- 0.6% of total versus 10.7 +/- 0.3%; P < 0.01). The intracellular content of TCDCA 180 min after the administration of 1 mM TCDCA alone was 20.8 +/- 0.7 nmol/mg protein, that after simultaneous administration of 1 mM DBcAMP, 16.2 +/- 1.0 nmol/mg protein, and that after the simultaneous administration of 0.1 mM papaverine, 38.5 +/- 1.9 nmol/mg protein. A clear correlation between the release of LDH from hepatocytes and the intracellular content of TCDCA was thus observed. When given together with 1 mM taurocholic acid (TCA) or 1 mM tauroursodeoxycholic acid (TUDCA), papaverine exerted little effect on cytotoxicity or intrahepatocytic bile acid content. When cells were bathed in a medium free of bile acid after pretreatment with 1 mM TCDCA and 1 mM DBcAMP, additional exposure to DBcAMP for 30 min significantly stimulated reduction of intracellular TCDCA content (30.2 +/- 0.4% of total versus 44.0 +/- 1.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Expression pattern of peptide and amino acid genes in digestive tract of transporter juvenile turbot ( Scophthalmus maximus L.)

    NASA Astrophysics Data System (ADS)

    Xu, Dandan; He, Gen; Mai, Kangsen; Zhou, Huihui; Xu, Wei; Song, Fei

    2016-04-01

    Turbot ( Scophthalmus maximus L.), a carnivorous fish species with high dietary protein requirement, was chosen to examine the expression pattern of peptide and amino acid transporter genes along its digestive tract which was divided into six segments including stomach, pyloric caeca, rectum, and three equal parts of the remainder of the intestine. The results showed that the expression of two peptide and eleven amino acid transporters genes exhibited distinct patterns. Peptide transporter 1 (PepT1) was rich in proximal intestine while peptide transporter 2 (PepT2) was abundant in distal intestine. A number of neutral and cationic amino acid transporters expressed richly in whole intestine including B0-type amino acid transporter 1 (B0AT1), L-type amino acid transporter 2 (LAT2), T-type amino acid transporter 1 (TAT1), proton-coupled amino acid transporter 1 (PAT1), y+L-type amino acid transporter 1 (y+LAT1), and cationic amino acid transporter 2 (CAT2) while ASC amino acid transporter 2 (ASCT2), sodium-coupled neutral amino acid transporter 2 (SNAT2), and y+L-type amino acid transporter 2 (y+LAT2) abundantly expressed in stomach. In addition, system b0,+ transporters (rBAT and b0,+AT) existed richly in distal intestine. These findings comprehensively characterized the distribution of solute carrier family proteins, which revealed the relative importance of peptide and amino acid absorption through luminal membrane. Our findings are helpful to understand the mechanism of the utilization of dietary protein in fish with a short digestive tract.

  15. The role of the neutral amino acid transporter SNAT2 in cell volume regulation.

    PubMed

    Franchi-Gazzola, R; Dall'Asta, V; Sala, R; Visigalli, R; Bevilacqua, E; Gaccioli, F; Gazzola, G C; Bussolati, O

    2006-01-01

    Sodium-dependent neutral amino acid transporter-2 (SNAT2), the ubiquitous member of SLC38 family, accounts for the activity of transport system A for neutral amino acids in most mammalian tissues. As the transport process performed by SNAT2 is highly energized, system A substrates, such as glutamine, glycine, proline and alanine, reach high transmembrane gradients and constitute major components of the intracellular amino acid pool. Moreover, through a complex array of exchange fluxes, involving other amino acid transporters, and of metabolic reactions, such as the synthesis of glutamate from glutamine, SNAT2 activity influences the cell content of most amino acids, thus determining the overall size and the composition of the intracellular amino acid pool. As amino acids represent a large fraction of cell organic osmolytes, changes of SNAT2 activity are followed by modifications in both cell amino acids and cell volume. This mechanism is utilized by many cell types to perform an effective regulatory volume increase (RVI) upon hypertonic exposure. Under these conditions, the expression of SNAT2 gene is induced and newly synthesized SNAT2 proteins are preferentially targeted to the cell membrane, leading to a significant increase of system A transport Vmax. In cultured human fibroblasts incubated under hypertonic conditions, the specific silencing of SNAT2 expression, obtained with anti-SNAT2 siRNAs, prevents the increase in system A transport activity, hinders the expansion of intracellular amino acid pool, and significantly delays cell volume recovery. These results demonstrate the pivotal role played by SNAT2 induction in the short-term hypertonic RVI and suggest that neutral amino acids behave as compatible osmolytes in hypertonically stressed cells.

  16. Nucleic acids encoding metal uptake transporters and their uses

    DOEpatents

    Schroeder, Julian I.; Antosiewicz, Danuta M.; Schachtman, Daniel P.; Clemens, Stephan

    1999-01-01

    The invention provides LCT1 nucleic acids which encode metal ion uptake transporters. The invention also provides methods of modulating heavy metal and alkali metal uptake in plants. The methods involve producing transgenic plants comprising a recombinant expression cassette containing an LCT1 nucleic acid linked to a plant promoter.

  17. Utilization of Lactic Acid by Fusarium oxysporum var. lini: Regulation of Transport and Metabolism

    PubMed Central

    Castro, Ieso M.; Loureiro-Dias, Maria C.

    1994-01-01

    Lactic acid was transported in Fusarium oxysporum var. lini ATCC 10960 by a saturable transport system that had a half-saturation constant of 56.6 ± 7.5 μM and a maximum velocity of 0.61 ± 0.10 mmol h-1 g-1 (dry weight) at 26°C and pH 5.0. This transport system was inducible and was not expressed in the presence of a repressing substrate. Evidence is presented that the anionic form lactate- was taken up by the cells. Propionic, acetic, pyruvic, and bromoacetic acids but not succinic acid competitively inhibited the transport of lactic acid. Bromoacetic acid, which was not metabolized, was taken up to a steady-state level when intracellular and extracellular concentrations were identical, indicating that the transport system was not accumulative. The enzymatic activity that was physiologically more relevant in the metabolism of lactic acid was lactate: ferricytochrome c oxidase. This enzyme did not exhibit stereospecifity and was induced by lactic acid. PMID:16349143

  18. Molecular Evolution of Plant AAP and LHT Amino Acid Transporters.

    PubMed

    Tegeder, Mechthild; Ward, John M

    2012-01-01

    Nitrogen is an essential mineral nutrient and it is often transported within living organisms in its reduced form, as amino acids. Transport of amino acids across cellular membranes requires proteins, and here we report the phylogenetic analysis across taxa of two amino acid transporter families, the amino acid permeases (AAPs) and the lysine-histidine-like transporters (LHTs). We found that the two transporter families form two distinct groups in plants supporting the concept that both are essential. AAP transporters seem to be restricted to land plants. They were found in Selaginella moellendorffii and Physcomitrella patens but not in Chlorophyte, Charophyte, or Rhodophyte algae. AAPs were strongly represented in vascular plants, consistent with their major function in phloem (vascular tissue) loading of amino acids for sink nitrogen supply. LHTs on the other hand appeared prior to land plants. LHTs were not found in chlorophyte algae Chlamydomonas reinhardtii and Volvox carterii. However, the characean alga Klebsormidium flaccidum encodes KfLHT13 and phylogenetic analysis indicates that it is basal to land plant LHTs. This is consistent with the hypothesis that characean algae are ancestral to land plants. LHTs were also found in both S. moellendorffii and P. patens as well as in monocots and eudicots. To date, AAPs and LHTs have mainly been characterized in Arabidopsis (eudicots) and these studies provide clues to the functions of the newly identified homologs. PMID:22645574

  19. Molecular Evolution of Plant AAP and LHT Amino Acid Transporters

    PubMed Central

    Tegeder, Mechthild; Ward, John M.

    2012-01-01

    Nitrogen is an essential mineral nutrient and it is often transported within living organisms in its reduced form, as amino acids. Transport of amino acids across cellular membranes requires proteins, and here we report the phylogenetic analysis across taxa of two amino acid transporter families, the amino acid permeases (AAPs) and the lysine–histidine-like transporters (LHTs). We found that the two transporter families form two distinct groups in plants supporting the concept that both are essential. AAP transporters seem to be restricted to land plants. They were found in Selaginella moellendorffii and Physcomitrella patens but not in Chlorophyte, Charophyte, or Rhodophyte algae. AAPs were strongly represented in vascular plants, consistent with their major function in phloem (vascular tissue) loading of amino acids for sink nitrogen supply. LHTs on the other hand appeared prior to land plants. LHTs were not found in chlorophyte algae Chlamydomonas reinhardtii and Volvox carterii. However, the characean alga Klebsormidium flaccidum encodes KfLHT13 and phylogenetic analysis indicates that it is basal to land plant LHTs. This is consistent with the hypothesis that characean algae are ancestral to land plants. LHTs were also found in both S. moellendorffii and P. patens as well as in monocots and eudicots. To date, AAPs and LHTs have mainly been characterized in Arabidopsis (eudicots) and these studies provide clues to the functions of the newly identified homologs. PMID:22645574

  20. Aphid amino acid transporter regulates glutamine supply to intracellular bacterial symbionts.

    PubMed

    Price, Daniel R G; Feng, Honglin; Baker, James D; Bavan, Selvan; Luetje, Charles W; Wilson, Alex C C

    2014-01-01

    Endosymbiotic associations have played a major role in evolution. However, the molecular basis for the biochemical interdependence of these associations remains poorly understood. The aphid-Buchnera endosymbiosis provides a powerful system to elucidate how these symbioses are regulated. In aphids, the supply of essential amino acids depends on an ancient nutritional symbiotic association with the gamma-proteobacterium Buchnera aphidicola. Buchnera cells are densely packed in specialized aphid bacteriocyte cells. Here we confirm that five putative amino acid transporters are highly expressed and/or highly enriched in Acyrthosiphon pisum bacteriocyte tissues. When expressed in Xenopus laevis oocytes, two bacteriocyte amino acid transporters displayed significant levels of glutamine uptake, with transporter ACYPI001018, LOC100159667 (named here as Acyrthosiphon pisum glutamine transporter 1, ApGLNT1) functioning as the most active glutamine transporter. Transporter ApGLNT1 has narrow substrate selectivity, with high glutamine and low arginine transport capacity. Notably, ApGLNT1 has high binding affinity for arginine, and arginine acts as a competitive inhibitor for glutamine transport. Using immunocytochemistry, we show that ApGLNT1 is localized predominantly to the bacteriocyte plasma membrane, a location consistent with the transport of glutamine from A. pisum hemolymph to the bacteriocyte cytoplasm. On the basis of functional transport data and localization, we propose a substrate feedback inhibition model in which the accumulation of the essential amino acid arginine in A. pisum hemolymph reduces the transport of the precursor glutamine into bacteriocytes, thereby regulating amino acid biosynthesis in the bacteriocyte. Structural similarities in the arrangement of hosts and symbionts across endosymbiotic systems suggest that substrate feedback inhibition may be mechanistically important in other endosymbioses.

  1. Xenobiotic, bile acid, and cholesterol transporters: function and regulation.

    PubMed

    Klaassen, Curtis D; Aleksunes, Lauren M

    2010-03-01

    Transporters influence the disposition of chemicals within the body by participating in absorption, distribution, and elimination. Transporters of the solute carrier family (SLC) comprise a variety of proteins, including organic cation transporters (OCT) 1 to 3, organic cation/carnitine transporters (OCTN) 1 to 3, organic anion transporters (OAT) 1 to 7, various organic anion transporting polypeptide isoforms, sodium taurocholate cotransporting polypeptide, apical sodium-dependent bile acid transporter, peptide transporters (PEPT) 1 and 2, concentrative nucleoside transporters (CNT) 1 to 3, equilibrative nucleoside transporter (ENT) 1 to 3, and multidrug and toxin extrusion transporters (MATE) 1 and 2, which mediate the uptake (except MATEs) of organic anions and cations as well as peptides and nucleosides. Efflux transporters of the ATP-binding cassette superfamily, such as ATP-binding cassette transporter A1 (ABCA1), multidrug resistance proteins (MDR) 1 and 2, bile salt export pump, multidrug resistance-associated proteins (MRP) 1 to 9, breast cancer resistance protein, and ATP-binding cassette subfamily G members 5 and 8, are responsible for the unidirectional export of endogenous and exogenous substances. Other efflux transporters [ATPase copper-transporting beta polypeptide (ATP7B) and ATPase class I type 8B member 1 (ATP8B1) as well as organic solute transporters (OST) alpha and beta] also play major roles in the transport of some endogenous chemicals across biological membranes. This review article provides a comprehensive overview of these transporters (both rodent and human) with regard to tissue distribution, subcellular localization, and substrate preferences. Because uptake and efflux transporters are expressed in multiple cell types, the roles of transporters in a variety of tissues, including the liver, kidneys, intestine, brain, heart, placenta, mammary glands, immune cells, and testes are discussed. Attention is also placed upon a variety of

  2. Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

    PubMed Central

    Aleksunes, Lauren M.

    2010-01-01

    Transporters influence the disposition of chemicals within the body by participating in absorption, distribution, and elimination. Transporters of the solute carrier family (SLC) comprise a variety of proteins, including organic cation transporters (OCT) 1 to 3, organic cation/carnitine transporters (OCTN) 1 to 3, organic anion transporters (OAT) 1 to 7, various organic anion transporting polypeptide isoforms, sodium taurocholate cotransporting polypeptide, apical sodium-dependent bile acid transporter, peptide transporters (PEPT) 1 and 2, concentrative nucleoside transporters (CNT) 1 to 3, equilibrative nucleoside transporter (ENT) 1 to 3, and multidrug and toxin extrusion transporters (MATE) 1 and 2, which mediate the uptake (except MATEs) of organic anions and cations as well as peptides and nucleosides. Efflux transporters of the ATP-binding cassette superfamily, such as ATP-binding cassette transporter A1 (ABCA1), multidrug resistance proteins (MDR) 1 and 2, bile salt export pump, multidrug resistance-associated proteins (MRP) 1 to 9, breast cancer resistance protein, and ATP-binding cassette subfamily G members 5 and 8, are responsible for the unidirectional export of endogenous and exogenous substances. Other efflux transporters [ATPase copper-transporting β polypeptide (ATP7B) and ATPase class I type 8B member 1 (ATP8B1) as well as organic solute transporters (OST) α and β] also play major roles in the transport of some endogenous chemicals across biological membranes. This review article provides a comprehensive overview of these transporters (both rodent and human) with regard to tissue distribution, subcellular localization, and substrate preferences. Because uptake and efflux transporters are expressed in multiple cell types, the roles of transporters in a variety of tissues, including the liver, kidneys, intestine, brain, heart, placenta, mammary glands, immune cells, and testes are discussed. Attention is also placed upon a variety of regulatory

  3. Intestinal dehydroascorbic acid (DHA) transport mediated by the facilitative sugar transporters, GLUT2 and GLUT8.

    PubMed

    Corpe, Christopher P; Eck, Peter; Wang, Jin; Al-Hasani, Hadi; Levine, Mark

    2013-03-29

    Intestinal vitamin C (Asc) absorption was believed to be mediated by the Na(+)-dependent ascorbic acid transporter SVCT1. However, Asc transport across the intestines of SVCT1 knock-out mice is normal indicating that alternative ascorbic acid transport mechanisms exist. To investigate these mechanisms, rodents were gavaged with Asc or its oxidized form dehydroascorbic acid (DHA), and plasma Asc concentrations were measured. Asc concentrations doubled following DHA but not Asc gavage. We hypothesized that the transporters responsible were facilitated glucose transporters (GLUTs). Using Xenopus oocyte expression, we investigated whether facilitative glucose transporters GLUT2 and GLUT5-12 transported DHA. Only GLUT2 and GLUT8, known to be expressed in intestines, transported DHA with apparent transport affinities (Km) of 2.33 and 3.23 mm and maximal transport rates (Vmax) of 25.9 and 10.1 pmol/min/oocyte, respectively. Maximal rates for DHA transport mediated by GLUT2 and GLUT8 in oocytes were lower than maximal rates for 2-deoxy-d-glucose (Vmax of 224 and 32 pmol/min/oocyte for GLUT2 and GLUT8, respectively) and fructose (Vmax of 406 and 116 pmol/min/oocyte for GLUT2 and GLUT8, respectively). These findings may be explained by differences in the exofacial binding of substrates, as shown by inhibition studies with ethylidine glucose. DHA transport activity in GLUT2- and GLUT8-expressing oocytes was inhibited by glucose, fructose, and by the flavonoids phloretin and quercetin. These studies indicate intestinal DHA transport may be mediated by the facilitative sugar transporters GLUT2 and GLUT8. Furthermore, dietary sugars and flavonoids in fruits and vegetables may modulate Asc bioavailability via inhibition of small intestinal GLUT2 and GLUT8.

  4. Transport Function of Rice Amino Acid Permeases (AAPs).

    PubMed

    Taylor, Margaret R; Reinders, Anke; Ward, John M

    2015-07-01

    The transport function of four rice (Oryza sativa) amino acid permeases (AAPs), OsAAP1 (Os07g04180), OsAAP3 (Os06g36180), OsAAP7 (Os05g34980) and OsAAP16 (Os12g08090), was analyzed by expression in Xenopus laevis oocytes and electrophysiology. OsAAP1, OsAAP7 and OsAAP16 functioned, similarly to Arabidopsis AAPs, as general amino acid permeases. OsAAP3 had a distinct substrate specificity compared with other rice or Arabidopsis AAPs. OsAAP3 transported the basic amino acids lysine and arginine well but selected against aromatic amino acids. The transport of basic amino acids was further analyzed for OsAAP1 and OsAAP3, and the results support the transport of both neutral and positively charged forms of basic amino acids by the rice AAPs. Cellular localization using the tandem enhanced green fluorescent protein (EGFP)-red fluorescent protein (RFP) reporter pHusion showed that OsAAP1 and OsAAP3 localized to the plasma membrane after transient expression in onion epidermal cells or stable expression in Arabidopsis. PMID:25907566

  5. Research on advanced transportation systems

    NASA Astrophysics Data System (ADS)

    Nagai, Hirokazu; Hashimoto, Ryouhei; Nosaka, Masataka; Koyari, Yukio; Yamada, Yoshio; Noda, Keiichirou; Shinohara, Suetsugu; Itou, Tetsuichi; Etou, Takao; Kaneko, Yutaka

    1992-08-01

    An overview of the researches on advanced space transportation systems is presented. Conceptual study is conducted on fly back boosters with expendable upper stage rocket systems assuming a launch capacity of 30 tons and returning to the launch site by the boosters, and prospect of their feasibility is obtained. Reviews are conducted on subjects as follows: (1) trial production of 10 tons sub scale engines for the purpose of acquiring hardware data and picking up technical problems for full scale 100 tons thrust engines using hydrocarbon fuels; (2) development techniques for advanced liquid propulsion systems from the aspects of development schedule, cost; (3) review of conventional technologies, and common use of component; (4) oxidant switching propulsion systems focusing on feasibility of Liquefied Air Cycle Engine (LACE) and Compressed Air Cycle Engine (CACE); (5) present status of slosh hydrogen manufacturing, storage, and handling; (6) construction of small high speed dynamometer for promoting research on mini pump development; (7) hybrid solid boosters under research all over the world as low-cost and clean propulsion systems; and (8) high performance solid propellant for upper stage and lower stage propulsion systems.

  6. Transported acid aerosols measured in southern Ontario

    NASA Astrophysics Data System (ADS)

    Keeler, Gerald J.; Spengler, John D.; Koutrakis, Petros; Allen, George A.; Raizenne, Mark; Stern, Bonnie

    During the period 29 June 1986-9 August 1986, a field health study assessing the acute health effects of air pollutants on children was conducted at a summer girls' camp on the northern shore of Lake Erie in SW Ontario. Continuous air pollution measurements of SO 2, O 3, NO x, particulate sulfates, light scattering, and meteorological measurements including temperature, dew point, and wind speed and direction were made. Twelve-hour integrated samples of size fractioned particles were also obtained using dichotomous samplers and Harvard impactors equipped with an ammonia denuder for subsequent hydrogen ion determination. Particulate samples were analyzed for trace elements by X-ray fluorescence and Neutron Activation, and for organic and elemental carbon by a thermal/optical technique. The measured aerosol was periodically very acidic with observed 12-h averaged H + concentrations in the range < 10-560 nmoles m -3. The aerosol H + appeared to represent the net strong acidity after H 2SO 4 reaction with NH 3(g). Average daytime concentrations were higher than night-time for aerosol H +, sulfate, fine mass and ozone. Prolonged episodes of atmospheric acidity, sulfate, and ozone were associated with air masses arriving at the measurement site from the west and from the southwest over Lake Erie. Sulfate concentrations measured at the lakeshore camp were more than twice those measured at inland sites during extreme pollution episodes. The concentration gradient observed with onshore flow was potentially due to enhanced deposition near the lakeshore caused by discontinuities in the meteorological fields in this region.

  7. Fatty acid transport and utilization for the developing brain.

    PubMed

    Edmond, J; Higa, T A; Korsak, R A; Bergner, E A; Lee, W N

    1998-03-01

    To determine the transport and utilization of dietary saturated, monounsaturated, and n-6 and n-3 polyunsaturated fatty acids for the developing brain and other organs, artificially reared rat pups were fed a rat milk substitute containing the perdeuterated (each 97 atom% deuterium) fatty acids, i.e., palmitic, stearic, oleic, linoleic, and linolenic, from day 7 after birth to day 14 as previously described. Fatty acids in lipid extracts of the liver, lung, kidney, and brain were analyzed by gas chromatography-mass spectrometry to determine their content of each of the deuterated fatty acids. The uptake and metabolism of perdeuterated fatty acid lead to the appearance of three distinct groups of isotopomers: the intact perdeuterated, the newly synthesized (with recycled deuterium), and the natural unlabeled fatty acid. The quantification of these isotopomers permits the estimation of uptake and de novo synthesis of these fatty acids. Intact perdeuterated palmitic, stearic, and oleic acids from the diet were found in liver, lung, and kidney, but not in brain. By contrast, perdeuterated linoleic acid was found in all these organs. Isotopomers of fatty acid from de novo synthesis were observed in palmitic, oleic, and stearic acids in all tissues. The highest enrichment of isotopomers with recycled deuterium was found in the brain. The data indicate that, during the brain growth spurt and the prelude to myelination, the major saturated and monounsaturated fatty acids in brain lipids are exclusively produced locally by de novo biosynthesis. Consequently, the n-6 and n-3 polyunsaturated fatty acids must be transported and delivered to the brain by highly specific mechanisms.

  8. Regulation of amino acid metabolic enzymes and transporters in plants.

    PubMed

    Pratelli, Réjane; Pilot, Guillaume

    2014-10-01

    Amino acids play several critical roles in plants, from providing the building blocks of proteins to being essential metabolites interacting with many branches of metabolism. They are also important molecules that shuttle organic nitrogen through the plant. Because of this central role in nitrogen metabolism, amino acid biosynthesis, degradation, and transport are tightly regulated to meet demand in response to nitrogen and carbon availability. While much is known about the feedback regulation of the branched biosynthesis pathways by the amino acids themselves, the regulation mechanisms at the transcriptional, post-transcriptional, and protein levels remain to be identified. This review focuses mainly on the current state of our understanding of the regulation of the enzymes and transporters at the transcript level. Current results describing the effect of transcription factors and protein modifications lead to a fragmental picture that hints at multiple, complex levels of regulation that control and coordinate transport and enzyme activities. It also appears that amino acid metabolism, amino acid transport, and stress signal integration can influence each other in a so-far unpredictable fashion.

  9. Radioisotope thermoelectric generator transport trailer system

    SciTech Connect

    Ard, K.E.; King, D.A.; Leigh, H.; Satoh, J.A.

    1995-01-20

    The Radioisotope Thermoelectric Generator (RTG) Transportation System, designated as System 100, comprises four major systems. The four major systems are designated as the Packaging System (System 120), Trailer System (System 140), Operations and Ancillary Equipment System (System 160), and Shipping and Receiving Facility Transport System (System 180). Packaging System (System 120), including the RTG packaging is licensed (regulatory) hardware; it is certified by the U.S. Department of Energy to be in accordance with Title 10, {ital Code} {ital of} {ital Federal} {ital Regulations}, Part 71 (10 CFR 71). System 140, System 160, and System 180 are nonlicensed (nonregulatory) hardware. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}

  10. Vesicular transport systems in fungi

    PubMed Central

    Rodrigues, Marcio L; Nosanchuk, Joshua D; Schrank, Augusto; Vainstein, Marilene H; Casadevall, Arturo; Nimrichter, Leonardo

    2014-01-01

    Canonical and unconventional mechanisms of secretion in many eukaryotic cells are relatively well known. In contrast to the situation in animal cells, mechanisms of secretion in fungi must include the capacity for trans-cell wall passage of macromolecules to the extracellular space. Although these mechanisms remain somewhat elusive, several studies in recent years have suggested that vesicular transport is required for trans-cell wall secretion of large molecules. Several fungal molecules, including proteins, lipids, polysaccharides and pigments, are released to the extracellular space in vesicles. In pathogenic fungi, a number of these vesicular components are associated with fungal virulence. Indeed, extracellular vesicles produced by fungi can interfere with the immunomodulatory activity of host cells. Fungal vesicles share many functional aspects with mammalian exosomes and extracellular vesicles produced by bacteria, plants and protozoa, but their cellular origin remains unknown. Here, we discuss the involvement of vesicular transport systems in fungal physiology and pathogenesis, making parallels with the mammalian, bacterial, protozoan and plant cell literature. PMID:22082294

  11. Phase stable RF transport system

    DOEpatents

    Curtin, Michael T.; Natter, Eckard F.; Denney, Peter M.

    1992-01-01

    An RF transport system delivers a phase-stable RF signal to a load, such as an RF cavity of a charged particle accelerator. A circuit generates a calibration signal at an odd multiple frequency of the RF signal where the calibration signal is superimposed with the RF signal on a common cable that connects the RF signal with the load. Signal isolating diplexers are located at both the RF signal source end and load end of the common cable to enable the calibration to be inserted and extracted from the cable signals without any affect on the RF signal. Any phase shift in the calibration signal during traverse of the common cable is then functionally related to the phase shift in the RF signal. The calibration phase shift is used to control a phase shifter for the RF signal to maintain a stable RF signal at the load.

  12. Light-activated amino acid transport in Halobacterium halobium envelope vesicles

    NASA Technical Reports Server (NTRS)

    Macdonald, R. E.; Lanyi, J. K.

    1977-01-01

    Vesicles prepared from Halobacterium halobium cell envelopes accumulate amino acids in response to light-induced electrical and chemical gradients. Nineteen of 20 commonly occurring amino acids have been shown to be actively accumulated by these vesicles in response to illumination or in response to an artificially created Na+ gradient. On the basis of shared common carriers the transport systems can be divided into eight classes, each responsible for the transport of one or several amino acids: arginine, lysine, histidine; asparagine, glutamine; alanine, glycine, threonine, serine; leucine, valine, isoleucine, methionine; phenylalanine, tyrosine, tryptophan; aspartate; glutamate; proline. Available evidence suggests that these carriers are symmetrical in that amino acids can be transported equally well in both directions across the vesicle membranes. A tentative working model to account for these observations is presented.

  13. Classical transport in disordered systems

    NASA Astrophysics Data System (ADS)

    Papaioannou, Antonios

    This thesis reports on the manifestation of structural disorder on molecular transport and it consists of two parts. Part I discusses the relations between classical transport and the underlying structural complexity of the system. Both types of molecular diffusion, namely Gaussian and non- Gaussian are presented and the relevant time regimes are discussed. In addition the concept of structural universality is introduced and connected with the diffusion metrics. One of the most robust techniques for measuring molecular mean square displacements is magnetic resonance. This method requires encoding and subsequently reading out after an experimentally controlled time, a phase φ to the spins using magnetic field gradients. The main limitation for probing short diffusion lengths L(t) ˜ 1micro m with magnetic resonance is the requirement to encode and decode the phase φ in very short time intervals. Therefore, to probe such displacements a special probe was developed equipped with a gradient coil capable of delivering magnetic field gradients of approximately 90 G/cmA . The design of the probe is reported. Part I also includes a discussion of experiments of transport in two qualitatively different disordered phantoms and reports on a direct observation of universality in one-dimension. The results reveal the universal power law scaling of the diffusion coefficient at the long-time regime and illustrate the essence of structural universality by experimentally determining the structure correlation function of the phantoms. In addition, the scaling of the diffusive permeability of the phantoms with respect to the pore size is investigated. Additional work presented includes a detailed study of adsorption of methane gas in Vycor disordered glass. The techniques described in Part I of this thesis are widely used for measuring structural parameters of porous media, such as the surface-to-volume ratio or diffusive permeability. Part II of this thesis discusses the

  14. Manned transportation system study - Evaluation of candidate transportation architectures

    NASA Technical Reports Server (NTRS)

    Lance, Nicholas; Klemer, R.; Sooter, C.

    1992-01-01

    The overall evaluation process, the tool developed to perform the evaluation, and the evaluation results in determining the right approach to meet the nation's mannned transportation needs are presented. To address the various considerations, architecture sets consisting of the candidate transportation systems are constructed. As this methodology results in multiple architectures to examine, an architecture evaluation tool was developed to facilitate the evaluation of the architecture attribute values from the system values of the attributes.

  15. Sustainability Analysis of Innovative Transport System

    NASA Astrophysics Data System (ADS)

    Meiere, Ieva; Bazbauers, Gatis

    2011-01-01

    The focus of the research is to develop a new approach to transport solution based on the use of a conveyortype system and to compare the environmental impact of the new system with the existing ones. The new transport system consists of a conveyor driven by an electric motor, with a wind power plant supplying electricity, hydrogen storage and a fuel cell for matching the wind power production with the motor load. The research tasks included the evaluation of the consumption of fossil fuels and the associated environmental impact of existing transport system and a comparison with energy consumption and associated environmental impact of the new system. The energy balance of the conveyor transport system was modelled on an hourly basis by using the EnergyPLAN computer program [1] which allows to analyze a combination of intermittent renewable energy technologies, storage and transport systems. The results show that the existing transport system has greater impact on the environment than the proposed one.

  16. The glutamate and neutral amino acid transporter family: physiological and pharmacological implications.

    PubMed

    Kanai, Yoshikatsu; Hediger, Matthias A

    2003-10-31

    The solute carrier family 1 (SLC1) is composed of five high affinity glutamate transporters, which exhibit the properties of the previously described system XAG-, as well as two Na+-dependent neutral amino acid transporters with characteristics of the so-called "ASC" (alanine, serine and cysteine). The SLC1 family members are structurally similar, with almost identical hydropathy profiles and predicted membrane topologies. The transporters have eight transmembrane domains and a structure reminiscent of a pore loop between the seventh and eighth domains [Neuron 21 (1998) 623]. However, each of these transporters exhibits distinct functional properties. Glutamate transporters mediate transport of L-Glu, L-Asp and D-Asp, accompanied by the cotransport of 3 Na+ and one 1 H+, and the countertransport of 1 K+, whereas ASC transporters mediate Na+-dependent exchange of small neutral amino acids such as Ala, Ser, Cys and Thr. Given the high concentrating capacity provided by the unique ion coupling pattern of glutamate transporters, they play crucial roles in protecting neurons against glutamate excitotoxicity in the central nervous system (CNS). The regulation and manipulation of their function is a critical issue in the pathogenesis and treatment of CNS disorders involving glutamate excitotoxicity. Loss of function of the glial glutamate transporter GLT1 (SLC1A2) has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), resulting in damage of adjacent motor neurons. The importance of glial glutamate transporters in protecting neurons from extracellular glutamate was further demonstrated in studies of the slc1A2 glutamate transporter knockout mouse. The findings suggest that therapeutic upregulation of GLT1 may be beneficial in a variety of pathological conditions. Selective inhibition of the neuronal glutamate transporter EAAC1 (SLC1A1) but not the glial glutamate transporters may be of therapeutic interest, allowing blockage of glutamate exit from

  17. Proton-linked sugar transport systems in bacteria.

    PubMed

    Henderson, P J

    1990-08-01

    The cell membranes of various bacteria contain proton-linked transport systems for D-xylose, L-arabinose, D-galactose, D-glucose, L-rhamnose, L-fucose, lactose, and melibiose. The melibiose transporter of E. coli is linked to both Na+ and H+ translocation. The substrate and inhibitor specificities of the monosaccharide transporters are described. By locating, cloning, and sequencing the genes encoding the sugar/H+ transporters in E. coli, the primary sequences of the transport proteins have been deduced. Those for xylose/H+, arabinose/H+, and galactose/H+ transport are homologous to each other. Furthermore, they are just as similar to the primary sequences of the following: glucose transport proteins found in a Cyanobacterium, yeast, alga, rat, mouse, and man; proteins for transport of galactose, lactose, or maltose in species of yeast; and to a developmentally regulated protein of Leishmania for which a function is not yet established. Some of these proteins catalyze facilitated diffusion of the sugar without cation transport. From the alignments of the homologous amino acid sequences, predictions of common structural features can be made: there are likely to be twelve membrane-spanning alpha-helices, possibly in two groups of six; there is a central hydrophilic region, probably comprised largely of alpha-helix; the highly conserved amino acid residues (40-50 out of 472-522 total) form discrete patterns or motifs throughout the proteins that are presumably critical for substrate recognition and the molecular mechanism of transport. Some of these features are found also in other transport proteins for citrate, tetracycline, lactose, or melibiose, the primary sequences of which are not similar to each other or to the homologous series of transporters. The glucose/Na+ transporter of rabbit and man is different in primary sequence to all the other sugar transporters characterized, but it is homologous to the proline/Na+ transporter of E. coli, and there is evidence

  18. Substrate specificity and transport mechanism of amino-acid transceptor Slimfast from Aedes aegypti

    PubMed Central

    Boudko, Dmitri Y.; Tsujimoto, Hitoshi; Rodriguez, Stacy D.; Meleshkevitch, Ella A.; Price, David P.; Drake, Lisa L.; Hansen, Immo A.

    2015-01-01

    Anautogenous mosquitoes depend on vertebrate blood as nutrient source for their eggs. A highly efficient set of membrane transporters mediates the massive movement of nutrient amino acids between mosquito tissues after a blood meal. Here we report the characterization of the amino-acid transporter Slimfast (Slif) from the yellow-fever mosquito Aedes aegypti using codon-optimized heterologous expression. Slif is a well-known component of the target-of-rapamycin signalling pathway and fat body nutrient sensor, but its substrate specificity and transport mechanism were unknown. We found that Slif transports essential cationic and neutral amino acids with preference for arginine. It has an unusual dual-affinity mechanism with only the high affinity being Na+ dependent. Tissue-specific expression and blood meal-dependent regulation of Slif are consistent with conveyance of essential amino acids from gut to fat body. Slif represents a novel transport system and type of transceptor for sensing and transporting essential amino acids during mosquito reproduction. PMID:26449545

  19. ΔpH-Dependent Amino Acid Transport into Plasma Membrane Vesicles Isolated from Sugar Beet (Beta vulgaris L.) Leaves

    PubMed Central

    Li, Zhen-Chang; Bush, Daniel R.

    1991-01-01

    Proton-coupled aliphatic, neutral amino acid transport was investigated in plasma membrane vesicles isolated from sugar beet (Beta vulgaris L., cv Great Western) leaves. Two neutral amino acid symport systems were resolved based on inter-amino acid transport competition and on large variations in the specific activity of each porter in different species. Competitive inhibition was observed for transport competition between alanine, methionine, glutamine, and leucine (the alanine group) and between isoleucine, valine, and threonine (the isoleucine group). The apparent Km and Ki values were similar for transport competition among amino acids within the alanine group. In contrast, the kinetics of transport competition between these two groups of amino acids did not fit a simple competitive model. Furthermore, members of the isoleucine group were weak transport antagonists of the alanine group. These results are consistent with two independent neutral amino acid porters. In support of that conclusion, the ratio of the specific activity of alanine transport versus isoleucine transport varied from two- to 13-fold in plasma membrane vesicles isolated from different plant species. This ratio would be expected to remain relatively stable if these amino acids were moving through a single transport system and, indeed, the ratio of alanine to glutamine transport varied less than twofold. Analysis of the predicted structure of the aliphatic, neutral amino acids in solution shows that isoleucine, valine, and threonine contain a branched methyl or hydroxyl group at the β-carbon position that places a dense electron cloud close to the α-amino group. This does not occur for the unbranched amino acids or those that branch further away, e.g. leucine. We hypothesize that this structural feature of isoleucine, valine, and threonine results in unfavorable steric interactions with the alanine transport system that limits their flux through this porter. Hydrophobicity and hydrated

  20. Acid-base transport in pancreas—new challenges

    PubMed Central

    Novak, Ivana; Haanes, Kristian A.; Wang, Jing

    2013-01-01

    Along the gastrointestinal tract a number of epithelia contribute with acid or basic secretions in order to aid digestive processes. The stomach and pancreas are the most extreme examples of acid (H+) and base (HCO−3) transporters, respectively. Nevertheless, they share the same challenges of transporting acid and bases across epithelia and effectively regulating their intracellular pH. In this review, we will make use of comparative physiology to enlighten the cellular mechanisms of pancreatic HCO−3 and fluid secretion, which is still challenging physiologists. Some of the novel transporters to consider in pancreas are the proton pumps (H+-K+-ATPases), as well as the calcium-activated K+ and Cl− channels, such as KCa3.1 and TMEM16A/ANO1. Local regulators, such as purinergic signaling, fine-tune, and coordinate pancreatic secretion. Lastly, we speculate whether dys-regulation of acid-base transport contributes to pancreatic diseases including cystic fibrosis, pancreatitis, and cancer. PMID:24391597

  1. Mammalian target of rapamycin signalling modulates amino acid uptake by regulating transporter cell surface abundance in primary human trophoblast cells.

    PubMed

    Rosario, Fredrick J; Kanai, Yoshikatsu; Powell, Theresa L; Jansson, Thomas

    2013-02-01

    Abnormal fetal growth increases the risk for perinatal complications and predisposes for the development of obesity, diabetes and cardiovascular disease later in life. Emerging evidence suggests that changes in placental amino acid transport directly contribute to altered fetal growth. However, the molecular mechanisms regulating placental amino acid transport are largely unknown. Here we combined small interfering (si) RNA-mediated silencing approaches with protein expression/localization and functional studies in cultured primary human trophoblast cells to test the hypothesis that mammalian target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) regulate amino acid transporters by post-translational mechanisms. Silencing raptor (inhibits mTORC1) or rictor (inhibits mTORC2) markedly decreased basal System A and System L amino acid transport activity but had no effect on growth factor-stimulated amino acid uptake. Simultaneous inhibition of mTORC1 and 2 completely inhibited both basal and growth factor-stimulated amino acid transport activity. In contrast, mTOR inhibition had no effect on serotonin transport. mTORC1 or mTORC2 silencing markedly decreased the plasma membrane expression of specific System A (SNAT2, SLC38A2) and System L (LAT1, SLC7A5) transporter isoforms without affecting global protein expression. In conclusion, mTORC1 and mTORC2 regulate human trophoblast amino acid transporters by modulating the cell surface abundance of specific transporter isoforms. This is the first report showing regulation of amino acid transport by mTORC2. Because placental mTOR activity and amino acid transport are decreased in human intrauterine growth restriction our data are consistent with the possibility that dysregulation of placental mTOR plays an important role in the development of abnormal fetal growth.

  2. Hydrofluoric and nitric acid transport through lipid bilayer membranes.

    PubMed

    Gutknecht, J; Walter, A

    1981-06-01

    Hydrofluoric and nitric acid transport through lipid bilayer membranes were studied by a combination of electrical conductance and pH electrode techniques. Transport occurs primarily by nonionic diffusion of molecular HF and HNO3. Membrane permeabilities to HF and HNO3 ranged from 10(-4) to 10(-3) cm . s-1, five to seven orders of magnitude higher than the permeabilities to NO-3, F- and H+. Our results are consistent with the hypothesis that F- transport through biological membranes occurs mainly by nonionic diffusion of HF. Our results also suggest that of the two principal components of 'acid rain', HNO3 may be more toxic than H2SO4.

  3. Transport in closed nanoscale systems

    NASA Astrophysics Data System (ADS)

    Bushong, Neil

    2005-03-01

    An alternative way to describe electrical transport in nanoscale systems has been recently proposed where two large but finite charged electrodes discharge across a nanoscale junction (M. Di Ventra and T. Todorov, J. Phys. Cond. Matt. 16, 8025 (2004)). We have applied this concept to describe the dynamics of a finite quasi-one dimensional gold wire using both a simple tight-binding model and time-dependent density-functional theory. After an initial transient, a quasi-steady state sets in whose lifetime increases with system size. This quasi-steady state is due to the wave properties of the electron wavefunctions and the resultant uncertainty principle and is established without inelastic effects. The corresponding current-voltage characteristics at steady state are in very good agreement with those calculated from the static scattering approach. We discuss local electron distributions, electrostatic potentials, and local resistivity dipoles formed at the quasi-steady state and compare these findings with the static open-boundary problem. A relation between information entropy and electron dynamics is discussed. Work supported by NSF.

  4. Transport of phytanic acid on lipoproteins in Refsum disease.

    PubMed

    Wierzbicki, A S; Sankaralingam, A; Lumb, P J; Hardman, T C; Sidey, M C; Gibberd, F B

    1999-02-01

    Patients with Refsum disease accumulate significant quantities of phytanic acid in adipose and neural tissue. The accumulation can be reversed by following a diet low in phytanic acid, yet the mechanism of transport of this fatty acid is obscure. We investigated the distribution of phytanic acid in different lipoprotein subfractions in 11 patients with Refsum disease and 9 unaffected siblings. Plasma phytanic acid was distributed on VLDL (16.2% +/- 12.2%), IDL (1.77% +/- 1.64%), LDL (34.8% +/- 12.6%) and HDL (14.3% +/- 7.87%). No correlations with any parameter were seen with total phytanic acid content. Weak nonsignificant correlations were found with the fractional distribution of phytanic acid and VLDL triglyceride (r = 0.35; p = 0.12) and plasma HDL-cholesterol (r = 0.32; p = 0.16) and with LDL:HDL cholesterol ratio (r = 0.33; p = 0.14). Significant correlation of the fractional distribution of phytanic acid on lipoprotein particles was noted with the ratio of apolipoprotein B: apolipoprotein A1-containing particles (r = 0.46; p = 0.03) and apolipoprotein B: apolipoprotein A1 in HDL2 (r = 0.53; p = 0.01). This suggests that the import-export balance for phytanic acid in plasma is related to forward and reverse cholesterol transport on lipoprotein particles, and only weakly to plasma cholesterol and triglycerides. These ratios of apolipoprotein particles may play a significant role in determining the rate of phytanic acid elimination in patients with Refsum disease.

  5. L-aspartic acid transport by cat erythrocytes

    SciTech Connect

    Chen, C.W.; Preston, R.L.

    1986-03-01

    Cat and dog red cells are unusual in that they have no Na/K ATPase and contain low K and high Na intracellularly. They also show significant Na dependent L-aspartate (L-asp) transport. The authors have characterized this system in cat RBCs. The influx of /sup 3/H-L-asp (typically 2..mu..M) was measured in washed RBCs incubated for 60 s at 37/sup 0/C in medium containing 140 mM NaCl, 5 mM Kcl, 2 mM CaCl/sub 2/, 15 mM MOPS pH 7.4, 5 mM glucose, and /sup 14/C-PEG as a space marker. The cells were washed 3 times in the medium immediately before incubation which was terminated by centrifuging the RBCs through a layer of dibutylphthalate. Over an L-asp concentration range of 0.5-1000..mu..M, influx obeyed Michaelis-Menten kinetics with a small added linear diffusion component. The Kt and Jmax of the saturable component were 5.40 +/- 0.34 ..mu..M and 148.8 +/- 7.2 ..mu..mol 1. cell/sup -1/h/sup -1/ respectively. Replacement of Na with Li, K, Rb, Cs or choline reduce influx to diffusion. With the addition of asp analogues (4/sup +/M L-asp, 40/sup +/M inhibitor), the following sequence of inhibition was observed (range 80% to 40% inhib.): L-glutamate > L-cysteine sulfonate > D-asp > L-cysteic acid > D-glutamate. Other amino acids such as L-alanine, L-proline, L-lysine, L-cysteine, and taurine showed no inhibition (<5%). These data suggest that cat red cells contain a high-affinity Na dependent transport system for L-asp, glutamate, and closely related analogues which resembles that found in the RBCs of other carnivores and in neural tissues.

  6. A National MagLev Transportation System

    NASA Technical Reports Server (NTRS)

    Wright, Michael R.

    2003-01-01

    The case for a national high-speed magnetic-levitation (MagLev) transportation system is presented. Focus is on current issues facing the country, such as national security, the economy, transportation, technology, and the environment. NASA s research into MagLev technology for launch assist is also highlighted. Further, current socio-cultural norms regarding motor-vehicle-based transportation systems are questioned in light of the problems currently facing the U.S. The multidisciplinary benefits of a long-distance MagLev system support the idea that such a system would be an important element of a truly multimodal U.S. transportation infrastructure.

  7. Intelligent transportation systems applications to transportation demand management. Final report

    SciTech Connect

    Wallace, C.E.; Kilpatrick, A.K.; Schneider, K.R.

    1996-04-01

    The primary focus of Intelligent Transportation Systems (ITS) is on traffic management systems, advanced traveler information systems, and so forth. Further, ITS is most readily identified with such systems urban areas because the majority of transportation management infrastructures and traffic congestion exist in these densely populated areas. ITS however, must not be restricted to supply-side options. Transportation demand management (TDM) can potentially have a significant impact on congestion, energy conservation and the environment. This paper presents the results of a preliminary study of ITS implications for TDM. It reports on a number of related projects undertaken around the U.S. and in Canada. It offers recommendations for expanding ITS involvement in TDM.

  8. Reactive Transport Modeling of Acid Gas Generation and Condensation

    SciTech Connect

    G. Zhahg; N. Spycher; E. Sonnenthal; C. Steefel

    2005-01-25

    Pulvirenti et al. (2004) recently conducted a laboratory evaporation/condensation experiment on a synthetic solution of primarily calcium chloride. This solution represents one potential type of evaporated pore water at Yucca Mountain, Nevada, a site proposed for geologic storage of high-level nuclear waste. These authors reported that boiling this solution to near dryness (a concentration factor >75,000 relative to actual pore waters) leads to the generation of acid condensate (pH 4.5) presumably due to volatilization of HCl (and minor HF and/or HNO{sub 3}). To investigate the various processes taking place, including boiling, gas transport, and condensation, their experiment was simulated by modifying an existing multicomponent and multiphase reactive transport code (TOUGHREACT). This code was extended with a Pitzer ion-interaction model to deal with high ionic strength. The model of the experiment was set-up to capture the observed increase in boiling temperature (143 C at {approx}1 bar) resulting from high concentrations of dissolved salts (up to 8 m CaCl{sub 2}). The computed HCI fugacity ({approx} 10{sup -4} bars) generated by boiling under these conditions is not sufficient to lower the pH of the condensate (cooled to 80 and 25 C) down to observed values unless the H{sub 2}O mass fraction in gas is reduced below {approx}10%. This is because the condensate becomes progressively diluted by H{sub 2}O gas condensation. However, when the system is modeled to remove water vapor, the computed pH of instantaneous condensates decreases to {approx}1.7, consistent with the experiment (Figure 1). The results also show that the HCl fugacity increases, and calcite, gypsum, sylvite, halite, MgCl{sub 2}4H{sub 2}O and CaCl{sub 2} precipitate sequentially with increasing concentration factors.

  9. Transporters for cationic amino acids in animal cells: discovery, structure, and function.

    PubMed

    Devés, R; Boyd, C A

    1998-04-01

    The structure and function of the four cationic amino acid transporters identified in animal cells are discussed. The systems differ in specificity, cation dependence, and physiological role. One of them, system y+, is selective for cationic amino acids, whereas the others (B[0,+], b[0,+], and y+ L) also accept neutral amino acids. In recent years, cDNA clones related to these activities have been isolated. Thus two families of proteins have been identified: 1) CAT or cationic amino acid transporters and 2) BAT or broad-scope transport proteins. In the CAT family, three genes encode for four different isoforms [CAT-1, CAT-2A, CAT-2(B) and CAT-3]; these are approximately 70-kDa proteins with multiple transmembrane segments (12-14), and despite their structural similarity, they differ in tissue distribution, kinetics, and regulatory properties. System y+ is the expression of the activity of CAT transporters. The BAT family includes two isoforms (rBAT and 4F2hc); these are 59- to 78-kDa proteins with one to four membrane-spanning segments, and it has been proposed that these proteins act as transport regulators. The expression of rBAT and 4F2hc induces system b[0,+] and system y+ L activity in Xenopus laevis oocytes, respectively. The roles of these transporters in nutrition, endocrinology, nitric oxide biology, and immunology, as well as in the genetic diseases cystinuria and lysinuric protein intolerance, are reviewed. Experimental strategies, which can be used in the kinetic characterization of coexpressed transporters, are also discussed.

  10. A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance.

    PubMed

    Jang, Cholsoon; Oh, Sungwhan F; Wada, Shogo; Rowe, Glenn C; Liu, Laura; Chan, Mun Chun; Rhee, James; Hoshino, Atsushi; Kim, Boa; Ibrahim, Ayon; Baca, Luisa G; Kim, Esl; Ghosh, Chandra C; Parikh, Samir M; Jiang, Aihua; Chu, Qingwei; Forman, Daniel E; Lecker, Stewart H; Krishnaiah, Saikumari; Rabinowitz, Joshua D; Weljie, Aalim M; Baur, Joseph A; Kasper, Dennis L; Arany, Zoltan

    2016-04-01

    Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear. Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species, a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGC1a (also known as PGC-1α; encoded by Ppargc1a), a transcriptional coactivator that regulates broad programs of fatty acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty acid transport, stimulates muscle fatty acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1α to promote endothelial fatty acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the metabolite 3-HIB, by regulating the trans-endothelial flux of fatty acids, links the regulation of fatty acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes. PMID:26950361

  11. Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissue

    PubMed Central

    Salameh, Ahmad; Daquinag, Alexes C.; Staquicini, Daniela I.; An, Zhiqiang; Pasqualini, Renata; Kolonin, Mikhail G.

    2016-01-01

    We have previously identified prohibitin (PHB) and annexin A2 (ANX2) as proteins interacting on the surface of vascular endothelial cells in white adipose tissue (WAT) of humans and mice. Here, we demonstrate that ANX2 and PHB also interact in adipocytes. Mice lacking ANX2 have normal WAT vascularization, adipogenesis, and glucose metabolism but display WAT hypotrophy due to reduced fatty acid uptake by WAT endothelium and adipocytes. By using cell culture systems in which ANX2/PHB binding is disrupted either genetically or through treatment with a blocking peptide, we show that fatty acid transport efficiency relies on this protein complex. We also provide evidence that the interaction between ANX2 and PHB mediates fatty acid transport from the endothelium into adipocytes. Moreover, we demonstrate that ANX2 and PHB form a complex with the fatty acid transporter CD36. Finally, we show that the colocalization of PHB and CD36 on adipocyte surface is induced by extracellular fatty acids. Together, our results suggest that an unrecognized biochemical interaction between ANX2 and PHB regulates CD36-mediated fatty acid transport in WAT, thus revealing a new potential pathway for intervention in metabolic diseases. PMID:27468426

  12. Adsorption and transport of polymaleic acid on Callovo-Oxfordian clay stone: Batch and transport experiments

    NASA Astrophysics Data System (ADS)

    Durce, Delphine; Landesman, Catherine; Grambow, Bernd; Ribet, Solange; Giffaut, Eric

    2014-08-01

    Dissolved Organic Matter (DOM) can affect the mobility of radionuclides in pore water of clay-rich geological formations, such as those intended to be used for nuclear waste disposal. The present work studies the adsorption and transport properties of a polycarboxylic acid, polymaleic acid (PMA, Mw = 1.9 kDa), on Callovo-Oxfordian argillite samples (COx). Even though this molecule is rather different from the natural organic matter found in clay rock, the study of its retention properties on both dispersed and intact samples allows assessing to which extent organic acids may undergo sorption under natural conditions (pH 7) and what could be the impact on their mobility. PMA sorption and desorption were investigated in dispersed systems. The degree of sorption was measured after 1, 8 and 21 days and for a range of PMA initial concentrations from 4.5 × 10- 7 to 1.4 × 10- 3 mol.L- 1. The reversibility of the sorption process was estimated by desorption experiments performed after the sorption experiments. At the sorption steady state, the sorption was described by a two-site Langmuir model. A total sorption capacity of COx for PMA was found to be 1.01×10- 2 mol.kg- 1 distributed on two sorption sites, one weak and one strong. The desorption of PMA was incomplete, independently of the duration of the sorption phase. The amount of desorbable PMA even appeared to decrease for sorption phases from 1 to 21 days. To describe the apparent desorption hysteresis, two conceptual models were applied. The two-box diffusion model accounted for intraparticle diffusion and more generally for nonequilibrium processes. The two-box first-order non-reversible model accounted for a first-order non-reversible sorption and more generally for kinetically-controlled irreversible sorption processes. The use of the two models revealed that desorption hysteresis was not the result of nonequilibrium processes but was due to irreversible sorption. Irreversible sorption on the strong site was

  13. Energization of amino acid transport in energy-depleted Ehrlich cells and plasma membrane vesicles.

    PubMed

    Ohsawa, M; Kilberg, M S; Kimmel, G; Christensen, H N

    1980-06-20

    We redirect attention to contributions to the energization, of the active transport of amino acids in the Ehrlich cell, beyond the known energization, by down-gradient comigration of Na+, beyond possible direct energization by coupling to ATP breakdown, and beyond known energization by exchange with prior accumulations of amino acids. We re-emphasize the uphill operation of System L, and by prior depletion of cellular amino acids show that this system must receive energy beyond that made available by their coupled exodus. After this depletion the Na+-indepdendent accumulation of the norbornane amino acid, 2-aminobicycloheptane-2-carboxylic acid becomes strongly subject to stimulation by incubation with glucose. Energy transfer between Systems A and L through the mutual substrate action of ordinary amino acids was minimized although not entirely avoided by the use of amino acid analogs specific to each system. When 2,4-dinitrophenol was included in the depleting treatment, and pyruvate, phenazine methosulfate, or glucose used for restoration, recovery of uptake of the norbornane amino acid was independent of external Na+ or K+ levels. Restoration or the uptake of 2-(methylamino)isobutyric acid was, however, decreased by omission of external K+. Contrary to an earlier finding, restoration of uptake of each of these amino acids was associated with distinct and usually correlated rises in cellular ATP levels. ATP addition failed to stimulate exodus of the norbornane amino acid from plasma membrane vesicles, although either NADH or phenazine methosulfate did stimulate exodus. ATP production and use is thus associated with transport energization although evidence for a direct role failed to appear.

  14. Transport of ascorbic acid and dehydroascorbic acid by pancreatic islet cells from neonatal rats.

    PubMed Central

    Zhou, A; Nielsen, J H; Farver, O; Thorn, N A

    1991-01-01

    Several amidated biologically active peptides such as pancreastatin, thyrotropin-releasing hormone, pancreatic polypeptide and amylin are produced in endocrine pancreatic tissue which contains the enzyme necessary for their final processing, i.e. peptidylglycine alpha-amidating mono-oxygenase (EC 1.14.17.3). The enzyme needs ascorbic acid for activity as well as copper and molecular oxygen. The present work shows that pancreatic islet cells prepared from overnight cultures of isolated islets from 5-7-day-old rats accumulate 14C-labelled ascorbic acid by a Na(+)-dependent active transport mechanism which involves a saturable process (estimated Km 17.6 microM). Transport was inhibited by ouabain, phloridzin, cytochalasin B, amiloride and probenecid. Glucose inhibited or stimulated uptake, depending on the length of incubation time of the cells. The uptake of dehydroascorbic acid was linearly dependent on concentration. Dehydroascorbic acid was converted to ascorbic acid by an unknown mechanism after uptake. The uptake of both ascorbic acid and dehydroascorbic acid was inhibited by tri-iodothyronine, and uptake of ascorbic acid, but not of dehydroascorbic acid, was inhibited by glucocorticoids. Isolated secretory granules contained a fairly low concentration of iron but a high concentration of copper. Images Fig. 6. PMID:2012602

  15. STARS: The Space Transportation Architecture Risk System

    NASA Technical Reports Server (NTRS)

    Greenberg, Joel S.

    1997-01-01

    Because of the need to perform comparisons between transportation systems that are likely to have significantly different levels of risk, both because of differing degrees of freedom in achieving desired performance levels and their different states of development and utilization, an approach has been developed for performing early comparisons of transportation architectures explicitly taking into account quantitative measures of uncertainty and resulting risk. The approach considers the uncertainty associated with the achievement of technology goals, the effect that the achieved level of technology will have on transportation system performance and the relationship between transportation system performance/capability and the ability to accommodate variations in payload mass. The consequences of system performance are developed in terms of expected values and associated standard deviations of nonrecurring, recurring and the present value of transportation system life cycle cost. Typical results are presented to illustrate the application of the methodology.

  16. Aging differentially affects human skeletal muscle amino acid transporter expression when essential amino acids are ingested after exercise

    PubMed Central

    Dickinson, Jared M.; Drummond, Micah J.; Coben, Jennifer R.; Volpi, Elena; Rasmussen, Blake B.

    2012-01-01

    Background & Aims Amino acid transporters have been proposed as regulators of protein synthesis. The primary aim of this study was to determine whether amino acid transporter expression is increased in human muscle following resistance exercise (RE) coupled with essential amino acid (EAA) ingestion, and whether a differential response occurs with aging. Secondly, we aimed to compare this response to a previous study examining RE alone. Methods Young (n=7, 30±2yr) and older men (n=6, 70±2yr) ingested EAA 1h after RE. Muscle biopsies were obtained at rest and 3 and 6h postexercise to examine amino acid transporter mRNA and protein expression. Results In both age groups, RE+EAA increased mRNA of L-type amino acid transporter 1 (LAT1)/solute linked carrier (SLC)7A5, sodium-coupled neutral amino acid transporter 2 (SNAT2)/SLC38A2, and cationic amino acid transporter 1/SLC7A1 (p<0.05). SNAT2 protein increased in young at 3 and 6h (p<0.05), whereas old maintained higher LAT1 protein (p<0.05). Compared to RE alone, RE+EAA enhanced amino acid transporter expression only in young (p<0.05). Conclusions RE increases muscle amino acid transporter expression in young and older adults, however, postexercise EAA ingestion enhances amino acid transporter expression only in young indicating that aging may influence the function of specific amino acid transporters. PMID:22889597

  17. Abscisic acid transporters cooperate to control seed germination

    PubMed Central

    Kang, Joohyun; Yim, Sojeong; Choi, Hyunju; Kim, Areum; Lee, Keun Pyo; Lopez-Molina, Luis; Martinoia, Enrico; Lee, Youngsook

    2015-01-01

    Seed germination is a key developmental process that has to be tightly controlled to avoid germination under unfavourable conditions. Abscisic acid (ABA) is an essential repressor of seed germination. In Arabidopsis, it has been shown that the endosperm, a single cell layer surrounding the embryo, synthesizes and continuously releases ABA towards the embryo. The mechanism of ABA transport from the endosperm to the embryo was hitherto unknown. Here we show that four AtABCG transporters act in concert to deliver ABA from the endosperm to the embryo: AtABCG25 and AtABCG31 export ABA from the endosperm, whereas AtABCG30 and AtABCG40 import ABA into the embryo. Thus, this work establishes that radicle extension and subsequent embryonic growth are suppressed by the coordinated activity of multiple ABA transporters expressed in different tissues. PMID:26334616

  18. Transport in Halobacterium Halobium: Light-Induced Cation-Gradients, Amino Acid Transport Kinetics, and Properties of Transport Carriers

    NASA Technical Reports Server (NTRS)

    Lanyi, Janos K.

    1977-01-01

    Cell envelope vesicles prepared from H. halobium contain bacteriorhodopsin and upon illumination protons are ejected. Coupled to the proton motive force is the efflux of Na(+). Measurements of Na-22 flux, exterior pH change, and membrane potential, Delta(psi) (with the dye 3,3'-dipentyloxadicarbocyanine) indicate that the means of Na(+) transport is sodium/proton exchange. The kinetics of the pH changes and other evidence suggests that the antiport is electrogenic (H(+)/Na(++ greater than 1). The resulting large chemical gradient for Na(+) (outside much greater than inside), as well as the membrane potential, will drive the transport of 18 amino acids. The I9th, glutamate, is unique in that its accumulation is indifferent to Delta(psi): this amino acid is transported only when a chemical gradient for Na(+) is present. Thus, when more and more NaCl is included in the vesicles glutamate transport proceeds with longer and longer lags. After illumination the gradient of H+() collapses within 1 min, while the large Na(+) gradient and glutamate transporting activity persists for 10- 15 min, indicating that proton motive force is not necessary for transport. A chemical gradient of Na(+), arranged by suspending vesicles loaded with KCl in NaCl, drives glutamate transport in the dark without other sources of energy, with V(sub max) and K(sub m) comparable to light-induced transport. These and other lines of evidence suggest that the transport of glutamate is facilitated by symport with Na(+), in an electrically neutral fashion, so that only the chemical component of the Na(+) gradient is a driving force.

  19. The transportation operations system: A description

    SciTech Connect

    Best, R.E.; Danese, F.L.; Dixon, L.D.; Peterson, R.W. ); Pope, R.B. )

    1990-01-01

    This paper presents a description of the system for transporting radioactive waste that may be deployed to accomplish the assigned system mission, which includes accepting spent nuclear fuel (SNF) and high-level radioactive waste (HLW) from waste generator sites and transporting them to the FWMS destination facilities. The system description presented here contains, in part, irradiated fuel and waste casks, ancillary equipments, truck, rail, and barge transporters, cask and vehicle traffic management organizations, maintenance facilities, and other operations elements. The description is for a fully implemented system, which is not expected to be achieved, however, until several years after initial operations. 6 figs.

  20. Adaptive transport of folic acid across renal epithelia in folate-deficient rats.

    PubMed

    Wani, Nissar Ahmad; Kaur, Jyotdeep

    2012-11-01

    Folate (vitamin B(9)) is an essential vitamin for a wide spectrum of biochemical reactions; however, unlike bacteria and plants, mammals are devoid of folate biosynthesis and thus must obtain this cofactor from exogenous sources. The activities of folate transporters on the kidneys play an important role in conserving folate excretion and reabsorption across the apical membrane of the renal proximal tubules. The different transport system activities may become identifiable in response to external stimuli, such as folate availability and exposure to chemotherapeutic agents. We have explored the effect of folate deficiency on the activity and expression of folate transporters in rat kidneys. Wistar rats were fed a folate-containing diet (2 mg folic acid kg(-1) diet) or a folic acid-free diet over a 3-month period, and mechanisms of folate transport were studied in renal brush border membrane vesicles and basolateral membrane vesicles. The renal folate uptake process is saturable and pH dependent, and it involves the folate receptor and reduced folate carrier (RFC) systems and possibly the proton coupled folate transporter (PCFT) system. We found that folate deficiency increased the renal brush border membrane and basolateral folate uptake by increasing the number of transporter molecules. The observed up-regulation of mRNA expression was also associated with a significant increase in RFC and PCFT expression at the protein level.

  1. Systems Studies of DDT Transport

    ERIC Educational Resources Information Center

    Harrison, H. L.; And Others

    1970-01-01

    Major consequences of present and additional environmental quantities of DDT pesticide are predictable by mathematical models of transport, accumulation and concentration mechanisms in the Wisconsin regional ecosystem. High solubility and stability produce increased DDT concentrations at high organism trophic levels within world biosphere…

  2. Fatty Acid-binding Proteins Transport N-Acylethanolamines to Nuclear Receptors and Are Targets of Endocannabinoid Transport Inhibitors*

    PubMed Central

    Kaczocha, Martin; Vivieca, Stephanie; Sun, Jing; Glaser, Sherrye T.; Deutsch, Dale G.

    2012-01-01

    N-Acylethanolamines (NAEs) are bioactive lipids that engage diverse receptor systems. Recently, we identified fatty acid-binding proteins (FABPs) as intracellular NAE carriers. Here, we provide two new functions for FABPs in NAE signaling. We demonstrate that FABPs mediate the nuclear translocation of the NAE oleoylethanolamide, an agonist of nuclear peroxisome proliferator-activated receptor α (PPARα). Antagonism of FABP function through chemical inhibition, dominant-negative approaches, or shRNA-mediated knockdown reduced PPARα activation, confirming a requisite role for FABPs in this process. In addition, we show that NAE analogs, traditionally employed as inhibitors of the putative endocannabinoid transmembrane transporter, target FABPs. Support for the existence of the putative membrane transporter stems primarily from pharmacological inhibition of endocannabinoid uptake by such transport inhibitors, which are widely employed in endocannabinoid research despite lacking a known cellular target(s). Our approach adapted FABP-mediated PPARα signaling and employed in vitro binding, arachidonoyl-[1-14C]ethanolamide ([14C]AEA) uptake, and FABP knockdown to demonstrate that transport inhibitors exert their effects through inhibition of FABPs, thereby providing a molecular rationale for the underlying physiological effects of these compounds. Identification of FABPs as targets of transport inhibitors undermines the central pharmacological support for the existence of an endocannabinoid transmembrane transporter. PMID:22170058

  3. Neutralizing Aspartate 83 Modifies Substrate Translocation of Excitatory Amino Acid Transporter 3 (EAAT3) Glutamate Transporters*

    PubMed Central

    Hotzy, Jasmin; Machtens, Jan-Philipp; Fahlke, Christoph

    2012-01-01

    Excitatory amino acid transporters (EAATs) terminate glutamatergic synaptic transmission by removing glutamate from the synaptic cleft into neuronal and glial cells. EAATs are not only secondary active glutamate transporters but also function as anion channels. Gating of EAAT anion channels is tightly coupled to transitions within the glutamate uptake cycle, resulting in Na+- and glutamate-dependent anion currents. A point mutation neutralizing a conserved aspartic acid within the intracellular loop close to the end of transmembrane domain 2 was recently shown to modify the substrate dependence of EAAT anion currents. To distinguish whether this mutation affects transitions within the uptake cycle or directly modifies the opening/closing of the anion channel, we used voltage clamp fluorometry. Using three different sites for fluorophore attachment, V120C, M205C, and A430C, we observed time-, voltage-, and substrate-dependent alterations of EAAT3 fluorescence intensities. The voltage and substrate dependence of fluorescence intensities can be described by a 15-state model of the transport cycle in which several states are connected to branching anion channel states. D83A-mediated changes of fluorescence intensities, anion currents, and secondary active transport can be explained by exclusive modifications of substrate translocation rates. In contrast, sole modification of anion channel opening and closing is insufficient to account for all experimental data. We conclude that D83A has direct effects on the glutamate transport cycle and that these effects result in changed anion channel function. PMID:22532568

  4. Transportation Systems. Curriculum Guide for Technology Education.

    ERIC Educational Resources Information Center

    Chastain, Gary K.

    This curriculum guide for a 1-semester or 1-year course in transportation provides activities that show and explain many of the occupations, devices, and systems that are related to transportation on land, water, air, and space. The guide contains competencies (task lists), student competency records, and management sheets. Management sheets,…

  5. Aluminum in acidic surface waters: chemistry, transport, and effects.

    PubMed Central

    Driscoll, C T

    1985-01-01

    Ecologically significant concentrations of Al have been reported in surface waters draining "acid-sensitive" watersheds that are receiving elevated inputs of acidic deposition. It has been hypothesized that mineral acids from atmospheric deposition have remobilized Al previously precipitated within the soil during soil development. This Al is then thought to be transported to adjacent surface waters. Dissolved mononuclear Al occurs as aquo Al, as well as OH-, F-, SO4(2-), and organic complexes. Although past investigations have often ignored non-hydroxide complexes of Al, it appears that organic and F complexes are the predominant forms of Al in dilute (low ionic strength) acidic surface waters. The concentration of inorganic forms of Al increases exponentially with decreases in solution pH. This response is similar to the theoretical pH dependent solubility of Al mineral phases. The concentration of organic forms of Al, however, is strongly correlated with variations in organic carbon concentration of surface waters rather than pH. Elevated concentrations of Al in dilute acidic waters are of interest because: Al is an important pH buffer; Al may influence the cycling of important elements like P, organic carbon, and trace metals; and Al is potentially toxic to aquatic organisms. An understanding of the aqueous speciation of Al is essential for an evaluation of these processes. PMID:3935428

  6. Aluminum in acidic surface waters: chemistry, transport, and effects.

    PubMed

    Driscoll, C T

    1985-11-01

    Ecologically significant concentrations of Al have been reported in surface waters draining "acid-sensitive" watersheds that are receiving elevated inputs of acidic deposition. It has been hypothesized that mineral acids from atmospheric deposition have remobilized Al previously precipitated within the soil during soil development. This Al is then thought to be transported to adjacent surface waters. Dissolved mononuclear Al occurs as aquo Al, as well as OH-, F-, SO4(2-), and organic complexes. Although past investigations have often ignored non-hydroxide complexes of Al, it appears that organic and F complexes are the predominant forms of Al in dilute (low ionic strength) acidic surface waters. The concentration of inorganic forms of Al increases exponentially with decreases in solution pH. This response is similar to the theoretical pH dependent solubility of Al mineral phases. The concentration of organic forms of Al, however, is strongly correlated with variations in organic carbon concentration of surface waters rather than pH. Elevated concentrations of Al in dilute acidic waters are of interest because: Al is an important pH buffer; Al may influence the cycling of important elements like P, organic carbon, and trace metals; and Al is potentially toxic to aquatic organisms. An understanding of the aqueous speciation of Al is essential for an evaluation of these processes.

  7. Structural interaction with transportation and handling systems

    NASA Technical Reports Server (NTRS)

    1973-01-01

    Problems involved in the handling and transportation of finished space vehicles from the factory to the launch site are presented, in addition to recommendations for properly accounting for in space vehicle structural design, adverse interactions during transportation. Emphasis is given to the protection of vehicle structures against those environments and loads encountered during transportation (including temporary storage) which would exceed the levels that the vehicle can safely withstand. Current practices for verifying vehicle safety are appraised, and some of the capabilities and limitations of transportation and handling systems are summarized.

  8. MATE Transporter-Dependent Export of Hydroxycinnamic Acid Amides.

    PubMed

    Dobritzsch, Melanie; Lübken, Tilo; Eschen-Lippold, Lennart; Gorzolka, Karin; Blum, Elke; Matern, Andreas; Marillonnet, Sylvestre; Böttcher, Christoph; Dräger, Birgit; Rosahl, Sabine

    2016-02-01

    The ability of Arabidopsis thaliana to successfully prevent colonization by Phytophthora infestans, the causal agent of late blight disease of potato (Solanum tuberosum), depends on multilayered defense responses. To address the role of surface-localized secondary metabolites for entry control, droplets of a P. infestans zoospore suspension, incubated on Arabidopsis leaves, were subjected to untargeted metabolite profiling. The hydroxycinnamic acid amide coumaroylagmatine was among the metabolites secreted into the inoculum. In vitro assays revealed an inhibitory activity of coumaroylagmatine on P. infestans spore germination. Mutant analyses suggested a requirement of the p-coumaroyl-CoA:agmatine N4-p-coumaroyl transferase ACT for the biosynthesis and of the MATE transporter DTX18 for the extracellular accumulation of coumaroylagmatine. The host plant potato is not able to efficiently secrete coumaroylagmatine. This inability is overcome in transgenic potato plants expressing the two Arabidopsis genes ACT and DTX18. These plants secrete agmatine and putrescine conjugates to high levels, indicating that DTX18 is a hydroxycinnamic acid amide transporter with a distinct specificity. The export of hydroxycinnamic acid amides correlates with a decreased ability of P. infestans spores to germinate, suggesting a contribution of secreted antimicrobial compounds to pathogen defense at the leaf surface. PMID:26744218

  9. Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid.

    PubMed

    Nguyen, Long N; Ma, Dongliang; Shui, Guanghou; Wong, Peiyan; Cazenave-Gassiot, Amaury; Zhang, Xiaodong; Wenk, Markus R; Goh, Eyleen L K; Silver, David L

    2014-05-22

    Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is essential for normal brain growth and cognitive function. Consistent with its importance in the brain, DHA is highly enriched in brain phospholipids. Despite being an abundant fatty acid in brain phospholipids, DHA cannot be de novo synthesized in brain and must be imported across the blood-brain barrier, but mechanisms for DHA uptake in brain have remained enigmatic. Here we identify a member of the major facilitator superfamily--Mfsd2a (previously an orphan transporter)--as the major transporter for DHA uptake into brain. Mfsd2a is found to be expressed exclusively in endothelium of the blood-brain barrier of micro-vessels. Lipidomic analysis indicates that Mfsd2a-deficient (Mfsd2a-knockout) mice show markedly reduced levels of DHA in brain accompanied by neuronal cell loss in hippocampus and cerebellum, as well as cognitive deficits and severe anxiety, and microcephaly. Unexpectedly, cell-based studies indicate that Mfsd2a transports DHA in the form of lysophosphatidylcholine (LPC), but not unesterified fatty acid, in a sodium-dependent manner. Notably, Mfsd2a transports common plasma LPCs carrying long-chain fatty acids such LPC oleate and LPC palmitate, but not LPCs with less than a 14-carbon acyl chain. Moreover, we determine that the phosphor-zwitterionic headgroup of LPC is critical for transport. Importantly, Mfsd2a-knockout mice have markedly reduced uptake of labelled LPC DHA, and other LPCs, from plasma into brain, demonstrating that Mfsd2a is required for brain uptake of DHA. Our findings reveal an unexpected essential physiological role of plasma-derived LPCs in brain growth and function.

  10. Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid.

    PubMed

    Nguyen, Long N; Ma, Dongliang; Shui, Guanghou; Wong, Peiyan; Cazenave-Gassiot, Amaury; Zhang, Xiaodong; Wenk, Markus R; Goh, Eyleen L K; Silver, David L

    2014-05-22

    Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is essential for normal brain growth and cognitive function. Consistent with its importance in the brain, DHA is highly enriched in brain phospholipids. Despite being an abundant fatty acid in brain phospholipids, DHA cannot be de novo synthesized in brain and must be imported across the blood-brain barrier, but mechanisms for DHA uptake in brain have remained enigmatic. Here we identify a member of the major facilitator superfamily--Mfsd2a (previously an orphan transporter)--as the major transporter for DHA uptake into brain. Mfsd2a is found to be expressed exclusively in endothelium of the blood-brain barrier of micro-vessels. Lipidomic analysis indicates that Mfsd2a-deficient (Mfsd2a-knockout) mice show markedly reduced levels of DHA in brain accompanied by neuronal cell loss in hippocampus and cerebellum, as well as cognitive deficits and severe anxiety, and microcephaly. Unexpectedly, cell-based studies indicate that Mfsd2a transports DHA in the form of lysophosphatidylcholine (LPC), but not unesterified fatty acid, in a sodium-dependent manner. Notably, Mfsd2a transports common plasma LPCs carrying long-chain fatty acids such LPC oleate and LPC palmitate, but not LPCs with less than a 14-carbon acyl chain. Moreover, we determine that the phosphor-zwitterionic headgroup of LPC is critical for transport. Importantly, Mfsd2a-knockout mice have markedly reduced uptake of labelled LPC DHA, and other LPCs, from plasma into brain, demonstrating that Mfsd2a is required for brain uptake of DHA. Our findings reveal an unexpected essential physiological role of plasma-derived LPCs in brain growth and function. PMID:24828044

  11. Nucleic acid based logical systems.

    PubMed

    Han, Da; Kang, Huaizhi; Zhang, Tao; Wu, Cuichen; Zhou, Cuisong; You, Mingxu; Chen, Zhuo; Zhang, Xiaobing; Tan, Weihong

    2014-05-12

    Researchers increasingly visualize a significant role for artificial biochemical logical systems in biological engineering, much like digital logic circuits in electrical engineering. Those logical systems could be utilized as a type of servomechanism to control nanodevices in vitro, monitor chemical reactions in situ, or regulate gene expression in vivo. Nucleic acids (NA), as carriers of genetic information with well-regulated and predictable structures, are promising materials for the design and engineering of biochemical circuits. A number of logical devices based on nucleic acids (NA) have been designed to handle various processes for technological or biotechnological purposes. This article focuses on the most recent and important developments in NA-based logical devices and their evolution from in vitro, through cellular, even towards in vivo biological applications.

  12. Application of MS Transport Assays to the Four Human γ-Aminobutyric Acid Transporters.

    PubMed

    Schmitt, Sebastian; Höfner, Georg; Wanner, Klaus T

    2015-09-01

    γ-Aminobutyric acid (GABA) transporters (GATs) are promising drug targets for various diseases associated with imbalances in GABAergic neurotransmission. For the development of new drugs or pharmacological tools addressing GATs, screening techniques to identify new inhibitors and to characterize their potency at each GAT subtype are indispensable. By now, the technique by far dominating is based on radiolabeled GABA. We recently described "MS Transport Assays" for hGAT-1 by employing ((2) H6 )GABA as the substrate. In the present study, we applied this approach to all four human GAT subtypes and determined the KM values for GAT-mediated transport of ((2) H6 )GABA at each subtype. Furthermore, a comprehensive set of GAT inhibitors reflecting the whole range of potency and subtype selectivity known so far was evaluated for their potency. The comparison of pIC50 values obtained in conventional [(3) H]GABA uptake assays with those obtained in MS Transport Assays indicated the reliability of the latter. The MS Transport Assays enable a throughput similar to that of conventional radiometric transport assays performed in a 96-well format but avoid the use of radiolabeled substrates.

  13. Vesicular Inhibitory Amino Acid Transporter Is a Cl−/γ-Aminobutyrate Co-transporter*

    PubMed Central

    Juge, Narinobu; Muroyama, Akiko; Hiasa, Miki; Omote, Hiroshi; Moriyama, Yoshinori

    2009-01-01

    The vesicular inhibitory amino acid transporter (VIAAT) is a synaptic vesicle protein responsible for the vesicular storage of γ-aminobutyrate (GABA) and glycine which plays an essential role in GABAergic and glycinergic neurotransmission. The transport mechanism of VIAAT remains largely unknown. Here, we show that proteoliposomes containing purified VIAAT actively took up GABA upon formation of membrane potential (Δψ) (positive inside) but not ΔpH. VIAAT-mediated GABA uptake had an absolute requirement for Cl− and actually accompanied Cl− movement. Kinetic analysis indicated that one GABA molecule and two Cl− equivalents were transported during one transport cycle. VIAAT in which Glu213 was specifically mutated to alanine completely lost the ability to take up both GABA and Cl−. Essentially the same results were obtained with glycine, another substrate of VIAAT. These results demonstrated that VIAAT is a vesicular Cl− transporter that co-transports Cl− with GABA or glycine in a Δψ dependent manner. It is concluded that Cl− plays an essential role in vesicular storage of GABA and glycine. PMID:19843525

  14. Role of Secondary Transporters and Phosphotransferase Systems in Glucose Transport by Oenococcus oeni ▿

    PubMed Central

    Kim, Ok Bin; Richter, Hanno; Zaunmüller, Tanja; Graf, Sabrina; Unden, Gottfried

    2011-01-01

    Glucose uptake by the heterofermentative lactic acid bacterium Oenococcus oeni B1 was studied at the physiological and gene expression levels. Glucose- or fructose-grown bacteria catalyzed uptake of [14C]glucose over a pH range from pH 4 to 9, with maxima at pHs 5.5 and 7. Uptake occurred in two-step kinetics in a high- and low-affinity reaction. The high-affinity uptake followed Michaelis-Menten kinetics and required energization. It accumulated the radioactivity of glucose by a factor of 55 within the bacteria. A large portion (about 80%) of the uptake of glucose was inhibited by protonophores and ionophores. Uptake of the glucose at neutral pH was not sensitive to degradation of the proton potential, Δp. Expression of the genes OEOE_0819 and OEOE_1574 (here referred to as 0819 and 1574), coding for secondary transporters, was induced by glucose as identified by quantitative real-time (RT)-PCR. The genes 1574 and 0819 were able to complement growth of a Bacillus subtilis hexose transport-deficient mutant on glucose but not on fructose. The genes 1574 and 0819 therefore encode secondary transporters for glucose, and the transports are presumably Δp dependent. O. oeni codes, in addition, for a phosphotransferase transport system (PTS) (gene OEOE_0464 [0464] for the permease) with similarity to the fructose- and mannose-specific PTS of lactic acid bacteria. Quantitative RT-PCR showed induction of the gene 0464 by glucose and by fructose. The data suggest that the PTS is responsible for Δp-independent hexose transport at neutral pH and for the residual Δp-independent transport of hexoses at acidic pH. PMID:22020640

  15. Perfluorocarboxylic acid (PFCA) atmospheric formation and transport to the Arctic.

    NASA Astrophysics Data System (ADS)

    Pike-thackray, C.; Selin, N. E.

    2015-12-01

    Perfluorocarboxylic acids (PFCAs) are highly persistent and toxic environmental contaminants that have been found in remote locations such as the Arctic, far from emission sources. These persistent organic pollutants are emitted directly to the atmosphere as well as being produced by the degradation of precursor compounds in the atmosphere, but recent trends towards increasing precursor emissions and decreasing direct emissions raise the importance of production in the atmosphere. Our work aims to improve understanding of the atmospheric degradation of fluorotelomer precursor compounds to form the long-chain PFCAs PFOA (C8) and PFNA (C9).Using the atmospheric chemical transport model GEOS-Chem, which uses assimilated meteorology to simulate the atmospheric transport of trace gas species, we investigate the interaction of the atmospheric formation of PFCAs and the atmospheric transport of their precursor species. Our simulations are a first application of the GEOS-Chem framework to PFCA chemistry. We highlight the importance of the spatial and temporal variability of background atmospheric chemical conditions experienced during transport. We find that yields and formation times of PFOA and PFNA respond differently and strongly to the photochemical conditions of the atmosphere, such as the abundance of NO, HO2, and other photochemical species.

  16. Boric Acid Reclamation System (BARS)

    SciTech Connect

    Kniazewycz, B.G.; Markind, J.

    1986-03-01

    KLM Technologies' personnel have identified a Boric Acid Reclamation System (BARS) utilizing reverse osmosis and ultrafiltration to produce a recyclable grade of otherwise waste boric acid at PWRs, thus reducing a major source of low-level radwaste. The design of a prototype BARS as a compact volume reduction system was the result of KLM's Phase 1 Program, and based upon a preliminary feasibility program, which assessed the applicability of membrane technology to refurbish and recycle waste boric acid from floor and equipment drain streams. The analysis of the overall program indicated a substantial savings regarding off-site disposal costs. Today's economic scenario indicates that optimization of volume reduction operation procedures could significantly reduce waste management costs, especially where burial penalties have become more severe. As a reaction to the economic burden imposed by final disposal, many nuclear plants are currently modifying their design and operating philosophies concerning liquid radwaste processing systems to meet stricter environmental regulations, and to derive potential economic benefits by reducing the ever-increasing volumes of wastes that are produced. To effect these changes, innovative practices in waste management and more efficient processing technologies are being successfully implemented.

  17. Propulsion system for research VTOL transports

    NASA Technical Reports Server (NTRS)

    Gertsma, L. W.; Zigan, S.

    1973-01-01

    In anticipation of an eventual VTOL requirement for civil aviation, NASA has been conducting studies directed toward determining and developing the technology required for a commercial VTOL transport. In this paper, the commercial transport configurations are briefly reviewed; the propulsion system specifications and components developed by the engine study contractor are presented and described; and methods for using the lift-propulsion system for aircraft attitude control are discussed.

  18. The German Saenger space transportation system concept

    NASA Astrophysics Data System (ADS)

    Koelle, D. E.; Kuczera, H.; Hoegenauer, E.

    The vehicle configuration, performance criteria, and technological problems of the Saenger space transportation system are reviewed. The vehicle consists of a two-stage system, including a hypersonic first stage employing turboramjet propulsion. The cruise speed is Mach 4.4, with the capability to accelerate to Mach 6.8 prior to separation of the upper stage. Two different upper stages are proposed to fulfull the different requirements of manned space flight and unmanned payload transportation.

  19. Systemic Analysis Approaches for Air Transportation

    NASA Technical Reports Server (NTRS)

    Conway, Sheila

    2005-01-01

    Air transportation system designers have had only limited success using traditional operations research and parametric modeling approaches in their analyses of innovations. They need a systemic methodology for modeling of safety-critical infrastructure that is comprehensive, objective, and sufficiently concrete, yet simple enough to be used with reasonable investment. The methodology must also be amenable to quantitative analysis so issues of system safety and stability can be rigorously addressed. However, air transportation has proven itself an extensive, complex system whose behavior is difficult to describe, no less predict. There is a wide range of system analysis techniques available, but some are more appropriate for certain applications than others. Specifically in the area of complex system analysis, the literature suggests that both agent-based models and network analysis techniques may be useful. This paper discusses the theoretical basis for each approach in these applications, and explores their historic and potential further use for air transportation analysis.

  20. The WIPP transportation system: Dedicated to safety

    SciTech Connect

    Ward, T.; McFadden, M.

    1993-12-01

    When developing a transportation system to transport transuranic (TRU) waste from ten widely-dispersed generator sites, the Department of Energy (DOE) recognized and addressed many challenges. Shipments of waste to the Waste Isolation Pilot Plant (WIPP) were to cover a twenty-five year period and utilize routes covering over twelve thousand miles in twenty-three states. Enhancing public safety by maximizing the payload, thus reducing the number of shipments, was the primary objective. To preclude the requirement for overweight permits, the DOE started with a total shipment weight limit of 80,000 pounds and developed an integrated transportation system consisting of a Type ``B`` package to transport the material, a lightweight tractor and trailer, stringent driver requirements, and a shipment tracking system referred to as ``TRANSCOM``.

  1. Fire and materials modeling for transportation systems

    SciTech Connect

    Skocypec, R.D.; Gritzo, L.A.; Moya, J.L.; Nicolette, V.F.; Tieszen, S.R.; Thomas, R.

    1994-10-01

    Fire is an important threat to the safety of transportation systems. Therefore, understanding the effects of fire (and its interaction with materials) on transportation systems is crucial to quantifying and mitigating the impact of fire on the safety of those systems. Research and development directed toward improving the fire safety of transportation systems must address a broad range of phenomena and technologies, including: crash dynamics, fuel dispersion, fire environment characterization, material characterization, and system/cargo thermal response modeling. In addition, if the goal of the work is an assessment and/or reduction of risk due to fires, probabilistic risk assessment technology is also required. The research currently underway at Sandia National Laboratories in each of these areas is summarized in this paper.

  2. 49 CFR 37.25 - University transportation systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false University transportation systems. 37.25 Section 37.25 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Applicability § 37.25 University transportation systems....

  3. 49 CFR 37.25 - University transportation systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false University transportation systems. 37.25 Section 37.25 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Applicability § 37.25 University transportation systems....

  4. 49 CFR 37.25 - University transportation systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false University transportation systems. 37.25 Section 37.25 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Applicability § 37.25 University transportation systems....

  5. 49 CFR 37.25 - University transportation systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false University transportation systems. 37.25 Section 37.25 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Applicability § 37.25 University transportation systems....

  6. Design of a lunar transportation system

    NASA Technical Reports Server (NTRS)

    Sankaravelu, A.; Goddard, H.; Gold, R.; Greenwell, S.; Lander, J.; Nordell, B.; Stepp, K.; Styer, M.

    1989-01-01

    The development of a good transportation infrastructure is a major requirement for the establishment of a permanent lunar base. Transportation is characterized by the technology available in a specific time frame and the need to transport personnel and cargo between Earth and Moon, and between lunar bases. In our study, attention was first focused on developing a transportation system for the first generation lunar base. As a first step, a tracked-type multipurpose lunar transportation vehicle was considered as a possible mode of transportation and a detailed study was conducted on the various aspects of the vehicle. Since the vehicle is composed of many moving parts, exposing it to the environment of the Moon, where fine dust particles are prevalent, can cause problems associated with lubrication and friction. The vehicle also posed problems concerning weight and power. Hence, several modifications were made to the above design ideas conceptually, and a Lunar Articulated Remote Transportation System (Lunar ARTS) is proposed as a more effective alternative with the following objectives: (1) minimizing the transportation of construction material and fuel from Earth or maximizing the use of the lunar material; (2) use of novel materials and light-weight structures; (3) use of new manufacturing methods and technology such as magnetic levitation using superconducting materials; and (4) innovative concepts of effectively utilizing the exotic lunar conditions, i.e., high thermal gradients, lack of atmosphere, lower gravity, etc. To achieve the above objectives of designing transportation systems from concept to operation, the project was planned in three phases: (1) conceptual design; (2) detailed analysis and synthesis; and (3) construction, testing, evaluation, and operation. In this project, both phases 1 and 2 have been carried out and work on phase 3 is in progress. In this paper, the details of the Lunar ARTS are discussed and the future work on the vehicle are

  7. Hyperspectral imaging utility for transportation systems

    NASA Astrophysics Data System (ADS)

    Bridgelall, Raj; Rafert, J. Bruce; Tolliver, Denver

    2015-03-01

    The global transportation system is massive, open, and dynamic. Existing performance and condition assessments of the complex interacting networks of roadways, bridges, railroads, pipelines, waterways, airways, and intermodal ports are expensive. Hyperspectral imaging is an emerging remote sensing technique for the non-destructive evaluation of multimodal transportation infrastructure. Unlike panchromatic, color, and infrared imaging, each layer of a hyperspectral image pixel records reflectance intensity from one of dozens or hundreds of relatively narrow wavelength bands that span a broad range of the electromagnetic spectrum. Hence, every pixel of a hyperspectral scene provides a unique spectral signature that offers new opportunities for informed decision-making in transportation systems development, operations, and maintenance. Spaceborne systems capture images of vast areas in a short period but provide lower spatial resolution than airborne systems. Practitioners use manned aircraft to achieve higher spatial and spectral resolution, but at the price of custom missions and narrow focus. The rapid size and cost reduction of unmanned aircraft systems promise a third alternative that offers hybrid benefits at affordable prices by conducting multiple parallel missions. This research formulates a theoretical framework for a pushbroom type of hyperspectral imaging system on each type of data acquisition platform. The study then applies the framework to assess the relative potential utility of hyperspectral imaging for previously proposed remote sensing applications in transportation. The authors also introduce and suggest new potential applications of hyperspectral imaging in transportation asset management, network performance evaluation, and risk assessments to enable effective and objective decision- and policy-making.

  8. Regulation of hepatic bile acid transporters Ntcp and Bsep expression

    PubMed Central

    Cheng, Xingguo; Buckley, David; Klaassen, Curtis D.

    2009-01-01

    Sodium-taurocholate cotransporting polypeptide (Ntcp) and bile salt export pump (Bsep) are two key transporters for hepatic bile acid uptake and excretion. Alterations in Ntcp and Bsep expression have been reported in pathophysiological conditions. In the present study, the effects of age, gender, and various chemicals on the regulation of these two transporters were characterized in mice. Ntcp and Bsep mRNA levels in mouse liver were low in the fetus, but increased to its highest expression at parturition. After birth, mouse Ntcp and Bsep mRNA decreased by more than 50%, and then gradually increased to adult levels by day 30. Expression of mouse Ntcp mRNA and protein exhibit higher levels in female than male livers, which is consistent with the trend of human NTCP mRNA expression between men and women. No gender difference exists in BSEP/Bsep expression in human and mouse livers. Hormone replacements conducted in gonadectomized, hypophysectomized, and lit/lit mice indicate that female-predominant Ntcp expression in mouse liver is due to the inhibitory effect of male-pattern GH secretion, but not sex hormones. Ntcp and Bsep expression are in general resistant to induction by a large battery of microsomal enzyme inducers. Administration of cholestyramine increased Ntcp, whereas chenodeoxycholic acid increased Bsep mRNA expression. In silico analysis indicates that female-predominant mouse and human Ntcp/NTCP expression may be due to GH. In conclusion, mouse Ntcp and Bsep are regulated by age, gender, cholestyramine, and bile acid, but resistant to induction by most microsomal enzyme inducers. PMID:17897632

  9. Heteromeric amino acid transporters. In search of the molecular bases of transport cycle mechanisms.

    PubMed

    Palacín, Manuel; Errasti-Murugarren, Ekaitz; Rosell, Albert

    2016-06-15

    Heteromeric amino acid transporters (HATs) are relevant targets for structural studies. On the one hand, HATs are involved in inherited and acquired human pathologies. On the other hand, these molecules are the only known examples of solute transporters composed of two subunits (heavy and light) linked by a disulfide bridge. Unfortunately, structural knowledge of HATs is scarce and limited to the atomic structure of the ectodomain of a heavy subunit (human 4F2hc-ED) and distant prokaryotic homologues of the light subunits that share a LeuT-fold. Recent data on human 4F2hc/LAT2 at nanometer resolution revealed 4F2hc-ED positioned on top of the external loops of the light subunit LAT2. Improved resolution of the structure of HATs, combined with conformational studies, is essential to establish the structural bases for light subunit recognition and to evaluate the functional relevance of heavy and light subunit interactions for the amino acid transport cycle.

  10. Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors.

    PubMed

    Vuille-dit-Bille, Raphael N; Camargo, Simone M; Emmenegger, Luca; Sasse, Tom; Kummer, Eva; Jando, Julia; Hamie, Qeumars M; Meier, Chantal F; Hunziker, Schirin; Forras-Kaufmann, Zsofia; Kuyumcu, Sena; Fox, Mark; Schwizer, Werner; Fried, Michael; Lindenmeyer, Maja; Götze, Oliver; Verrey, François

    2015-04-01

    Sodium-dependent neutral amino acid transporter B(0)AT1 (SLC6A19) and imino acid (proline) transporter SIT1 (SLC6A20) are expressed at the luminal membrane of small intestine enterocytes and proximal tubule kidney cells where they exert key functions for amino acid (re)absorption as documented by their role in Hartnup disorder and iminoglycinuria, respectively. Expression of B(0)AT1 was shown in rodent intestine to depend on the presence of the carboxypeptidase angiotensin-converting enzyme 2 (ACE2). This enzyme belongs to the renin-angiotensin system and its expression is induced by treatment with ACE-inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) in many rodent tissues. We show here in the Xenopus laevis oocyte expression system that human ACE2 also functionally interacts with SIT1. To investigate in human intestine the potential effect of ACEIs or ARBs on ACE2, we analysed intestinal biopsies taken during routine gastroduodenoscopy and ileocolonoscopy from 46 patients of which 9 were under ACEI and 13 ARB treatment. Analysis of transcript expression by real-time PCR and of proteins by immunofluorescence showed a co-localization of SIT1 and B(0)AT1 with ACE2 in the brush-border membrane of human small intestine enterocytes and a distinct axial expression pattern of the tested gene products along the intestine. Patients treated with ACEIs displayed in comparison with untreated controls increased intestinal mRNA levels of ACE2, peptide transporter PEPT1 (SLC15A1) and AA transporters B(0)AT1 and PAT1 (SLC36A1). This study unravels in human intestine the localization and distribution of intestinal transporters involved in amino acid absorption and suggests that ACEIs impact on their expression.

  11. Not planning a sustainable transport system

    SciTech Connect

    Finnveden, Göran Åkerman, Jonas

    2014-04-01

    The overall objective of the Swedish transport policy is to ensure the economically efficient and sustainable provision of transport services for people and business throughout the country. More specifically, the transport sector shall, among other things, contribute to the achievement of environmental quality objectives in which the development of the transport system plays an important role in the achievement of the objectives. The aim of this study is to analyse if current transport planning supports this policy. This is done by analysing two recent cases: the National Infrastructure Plan 2010–2021, and the planning of Bypass Stockholm, a major road investment. Our results show that the plans are in conflict with several of the environmental quality objectives. Another interesting aspect of the planning processes is that the long-term climate goals are not included in the planning processes, neither as a clear goal nor as factor that will influence future transport systems. In this way, the long-term sustainability aspects are not present in the planning. We conclude that the two cases do not contribute to a sustainable transport system. Thus, several changes must be made in the processes, including putting up clear targets for emissions. Also, the methodology for the environmental assessments needs to be further developed and discussed. - Highlights: • Two cases are studied to analyse if current planning supports a sustainable transport system. • Results show that the plans are in conflict with several of the environmental quality objectives. • Long-term climate goals are not included in the planning processes. • Current practices do not contribute to a sustainable planning processes. • Methodology and process for environmental assessments must be further developed and discussed.

  12. Human Transportation System (HTS) study, volume 1

    NASA Technical Reports Server (NTRS)

    Lance, N.; Geyer, M. S.; Gaunce, M. T.

    1993-01-01

    Work completed under the Human Transportation System Study is summarized. This study was conducted by the New Initiatives Office at JSC with the technical support of Boeing, General Dynamics, Lockheed, McDonnell-Douglas, Martin Marietta, and Rockwell. The study was designed to generate information on determining the appropriate path to follow for new system development to meet the Nation's space transportation needs. The study evaluates 18 transportation architecture options using a parametric set of mission requirements. These options include use of current systems as well as proposed systems to assess the impact of various considerations, such as the cost of alternate access, or the benefit of separating people and cargo. The architecture options are compared to each other with six measurable evaluation criteria or attributes. They are the following: funding profile, human safety, probability of mission success, architecture cost risk, launch schedule confidence, and environmental impact. Values for these attributes are presented for the architecture options, with pertinent conclusions and recommendations.

  13. Human Transportation System (HTS) study: Executive summary

    NASA Technical Reports Server (NTRS)

    Lance, N.; Geyer, M. S.; Gaunce, M. T.

    1993-01-01

    Work completed under the Human Transportation System Study is summarized. This study was conducted by the New Initiatives Office at JSC with the technical support of Boeing, General Dynamics, Lockheed, McDonnell-Douglas, Martin Marietta, and Rockwell. The study was designed to generate information on determining the appropriate path to follow for new system development to meet the Nation's space transportation needs. The study evaluates 18 transportation architecture options using a parametric set of mission requirements. These options include use of current systems as well as proposed systems to assess the impact of various considerations, such as the cost of alternate access, or the benefit of separating people and cargo. The architecture options are compared to each other with six measurable evaluation criteria or attributes. They are the following: funding profile, human safety, probability of mission success, architecture cost risk, launch schedule confidence, and environmental impact. Values for these attributes are presented for the architecture options, with pertinent conclusions and recommendations.

  14. Transport of the two natural auxins, indole-3-butyric acid and indole-3-acetic acid, in Arabidopsis

    NASA Technical Reports Server (NTRS)

    Rashotte, Aaron M.; Poupart, Julie; Waddell, Candace S.; Muday, Gloria K.; Brown, C. S. (Principal Investigator)

    2003-01-01

    Polar transport of the natural auxin indole-3-acetic acid (IAA) is important in a number of plant developmental processes. However, few studies have investigated the polar transport of other endogenous auxins, such as indole-3-butyric acid (IBA), in Arabidopsis. This study details the similarities and differences between IBA and IAA transport in several tissues of Arabidopsis. In the inflorescence axis, no significant IBA movement was detected, whereas IAA is transported in a basipetal direction from the meristem tip. In young seedlings, both IBA and IAA were transported only in a basipetal direction in the hypocotyl. In roots, both auxins moved in two distinct polarities and in specific tissues. The kinetics of IBA and IAA transport appear similar, with transport rates of 8 to 10 mm per hour. In addition, IBA transport, like IAA transport, is saturable at high concentrations of auxin, suggesting that IBA transport is protein mediated. Interestingly, IAA efflux inhibitors and mutations in genes encoding putative IAA transport proteins reduce IAA transport but do not alter IBA movement, suggesting that different auxin transport protein complexes are likely to mediate IBA and IAA transport. Finally, the physiological effects of IBA and IAA on hypocotyl elongation under several light conditions were examined and analyzed in the context of the differences in IBA and IAA transport. Together, these results present a detailed picture of IBA transport and provide the basis for a better understanding of the transport of these two endogenous auxins.

  15. Advanced secondary power system for transport aircraft

    NASA Technical Reports Server (NTRS)

    Hoffman, A. C.; Hansen, I. G.; Beach, R. F.; Plencner, R. M.; Dengler, R. P.; Jefferies, K. S.; Frye, R. J.

    1985-01-01

    A concept for an advanced aircraft power system was identified that uses 20-kHz, 440-V, sin-wave power distribution. This system was integrated with an electrically powered flight control system and with other aircraft systems requiring secondary power. The resulting all-electric secondary power configuration reduced the empty weight of a modern 200-passenger, twin-engine transport by 10 percent and the mission fuel by 9 percent.

  16. Acid rain and transported air pollutants: implications for public policy

    SciTech Connect

    Not Available

    1984-06-01

    Acid rain, ozone, and fine particles in the air are endangering US resources, but controlling these pollutants will be expensive. These air pollutants harm lakes and streams, lower crop yields, damage manmade materials, decrease visibility and pose a threat to forests and human health. The costs to control these pollutants include higher electricity rates, fewer jobs for high-sulfur coal miners and financial strain to utilities and industries. Acid rain and other transported air pollutants pose a special problem for policymakers: how to balance the concerns of those who bear the risk of damage with those who will pay for the control. Scientific uncertainty about many aspects of the problem complicates the decision of whether or when to control. Additional scientific research will not provide an unambiguous answer in the near future, nor will it ever resolve value conflicts. The report synthesizes what is known about pollutant emissions, movements, and effects, and estimates the risk of potential damages to resources. OTA focuses on the public policy implications of the acid rain problems and estimates the costs and potential effectiveness of various control options.

  17. Increased Rat Placental Fatty Acid, but Decreased Amino Acid and Glucose Transporters Potentially Modify Intrauterine Programming.

    PubMed

    Nüsken, Eva; Gellhaus, Alexandra; Kühnel, Elisabeth; Swoboda, Isabelle; Wohlfarth, Maria; Vohlen, Christina; Schneider, Holm; Dötsch, Jörg; Nüsken, Kai-Dietrich

    2016-07-01

    Regulation of placental nutrient transport significantly affects fetal development and may modify intrauterine growth restriction (IUGR) and fetal programming. We hypothesized that placental nutrient transporters are differentially affected both by utero-placental insufficiency and prenatal surgical stress. Pregnant rats underwent bilateral uterine artery and vein ligation (LIG), sham operation (SOP) or no operation (controls, C) on gestational day E19. Placentas were obtained by caesarean section 4 h (LIG, n=20 placentas; SOP, n=24; C, n=12), 24 h (LIG, n=28; SOP, n=20; C, n=12) and 72 h (LIG, n=20; SOP, n=20; C, n=24) after surgery. Gene and protein expression of placental nutrient transporters for fatty acids (h-FABP, CD36), amino acids (SNAT1, SNAT2) and glucose (GLUT-1, Connexin 26) were examined by qRT-PCR, western blot and immunohistochemistry. Interestingly, the mean protein expression of h-FABP was doubled in placentas of LIG and SOP animals 4, 24 (SOP significant) and 72 h (SOP significant) after surgery. CD36 protein was significantly increased in LIG after 72 h. SNAT1 and SNAT2 protein and gene expressions were significantly reduced in LIG and SOP after 24 h. Further significantly reduced proteins were GLUT-1 in LIG (4 h, 72 h) and SOP (24 h), and Connexin 26 in LIG (72 h). In conclusion, placental nutrient transporters are differentially affected both by reduced blood flow and stress, probably modifying the already disturbed intrauterine milieu and contributing to IUGR and fetal programming. Increased fatty acid transport capacity may affect energy metabolism and could be a compensatory reaction with positive effects on brain development. J. Cell. Biochem. 117: 1594-1603, 2016. © 2015 Wiley Periodicals, Inc.

  18. Alternative battery systems for transportation uses

    SciTech Connect

    Michael Thackeray

    2012-07-25

    Argonne Distinguished Fellow Michael Thackeray highlights the need for alternative battery systems for transportation uses. Such systems will not only need to be smaller, lighter and more energy dense, but also able to make electric vehicles more competitive with internal combustion engine vehicles.

  19. Monte Carlo Nucleon Meson Transport Code System.

    2000-11-17

    Version 00 NMTC/JAERI97 is an upgraded version of the code system NMTC/JAERI, which was developed in 1982 at JAERI and is based on the CCC-161/NMTC code system. NMTC/JAERI97 simulates high energy nuclear reactions and nucleon-meson transport processes.

  20. Alternative battery systems for transportation uses

    ScienceCinema

    Michael Thackeray

    2016-07-12

    Argonne Distinguished Fellow Michael Thackeray highlights the need for alternative battery systems for transportation uses. Such systems will not only need to be smaller, lighter and more energy dense, but also able to make electric vehicles more competitive with internal combustion engine vehicles.

  1. Transport of. cap alpha. -aminoisobutyric acid by Streptococcus pyogenes and its derived L-form

    SciTech Connect

    Reizer, J.; Panos, C.

    1982-01-01

    We studied the uptake of ..cap alpha..-aminoisobutyric acid (AIB) in Streptococcus pyogenes and its physiologically isotonic L-form. S. pyogenes cells starved for glucose or treated with carbonyl cyanide-m-chlorophenyl hydrazone accumulated limited amounts of AIB. A high apparent K/sub m/ value characterized the glucose-independent transport of AIB. The rate and extent of AIB accumulation significantly increased in the presence of glucose. Two saturable transport components with distinct apparent K/sub m/values characterized glycolysis-coupled transport of AIB. A biphasic Lineweaver-Burk plot was also obtained for L-alanine transport by glycolyzing S. pyogenes cells. AIB seems to share a common transport system(s) with glycine, L- and D-anine, L-serine, and L-valine. This was shown by the competitive exchange efflux of accumulated AIB. About 30% of the AIB uptake was not inhibited by a saturating amount of L-valine, indicating the existence of more than one system for AIB transport, p-Chloromercuribenzoate markedly inhibited the accumulation of AIB by both glycolyzing and glucose-starved cells. In contrast, carbonyl cyanide-m-chlorophenyl hydrazone affected only metabolism-dependent uptake of AIB, which was also sensitive to dinitrophenol, N-ethylmaleimide, iodoacetate, fluoride (NaF), arsenate, and N,N'-dicyclohexylcarbodiimide. These results are interpreted according to the chemiosmotic theory of Mitchell, whereby a proton motive force constitutes the driving force for AIB accumulation. AIB was not accumulated by the L-form. However, a temporary accumulation of AIB by a counterflow mechanism and a saturable system with a low apparent affinity were demonstrated for AIB transport by this organism. We suggest that a deficiency in the coupling of energy to AIB transport is responsible for the apparent lack of active AIB accumulation by the L-form.

  2. Advanced Vehicle system concepts. [nonpetroleum passenger transportation

    NASA Technical Reports Server (NTRS)

    Hardy, K. S.; Langendoen, J. M.

    1983-01-01

    Various nonpetroleum vehicle system concepts for passenger vehicles in the 1990's are being considered as part of the Advanced Vehicle (AV) Assessment at the Jet Propulsion Laboratory. The vehicle system and subsystem performance requirements, the projected characteristics of mature subsystem candidates, and promising systems are presented. The system candidates include electric and hybrid vehicles powered by electricity with or without a nonpetroleum power source. The subsystem candidates include batteries (aqueous-mobile, flow, high-temperature, and metal-air), fuel cells (phosphoric acid, advanced acids, and solid polymer electrolyte), nonpetroleum heat engines, advanced dc and ac propulsion components, power-peaking devices, and transmissions.

  3. Folate and Vitamin B12 Transport Systems in the Developing Infant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    B vitamin transport systems in infants are not as well studied as those for amino acids and glucose. For most B vitamins, a 2-step process allows for digestion of coenzyme forms of the vitamins in food, followed by specific transport systems for the free vitamin in the intestine. Folate and vitamin ...

  4. The Integrated Air Transportation System Evaluation Tool

    NASA Technical Reports Server (NTRS)

    Wingrove, Earl R., III; Hees, Jing; Villani, James A.; Yackovetsky, Robert E. (Technical Monitor)

    2002-01-01

    Throughout U.S. history, our nation has generally enjoyed exceptional economic growth, driven in part by transportation advancements. Looking forward 25 years, when the national highway and skyway systems are saturated, the nation faces new challenges in creating transportation-driven economic growth and wealth. To meet the national requirement for an improved air traffic management system, NASA developed the goal of tripling throughput over the next 20 years, in all weather conditions while maintaining safety. Analysis of the throughput goal has primarily focused on major airline operations, primarily through the hub and spoke system.However, many suggested concepts to increase throughput may operate outside the hub and spoke system. Examples of such concepts include the Small Aircraft Transportation System, civil tiltrotor, and improved rotorcraft. Proper assessment of the potential contribution of these technologies to the domestic air transportation system requires a modeling capability that includes the country's numerous smaller airports, acting as a fundamental component of the National Air space System, and the demand for such concepts and technologies. Under this task for NASA, the Logistics Management Institute developed higher fidelity demand models that capture the interdependence of short-haul air travel with other transportation modes and explicitly consider the costs of commercial air and other transport modes. To accomplish this work, we generated forecasts of the distribution of general aviation based aircraft and GA itinerant operations at each of nearly 3.000 airport based on changes in economic conditions and demographic trends. We also built modules that estimate the demand for travel by different modes, particularly auto, commercial air, and GA. We examined GA demand from two perspectives: top-down and bottom-up, described in detail.

  5. A Robust Scalable Transportation System Concept

    NASA Technical Reports Server (NTRS)

    Hahn, Andrew; DeLaurentis, Daniel

    2006-01-01

    This report documents the 2005 Revolutionary System Concept for Aeronautics (RSCA) study entitled "A Robust, Scalable Transportation System Concept". The objective of the study was to generate, at a high-level of abstraction, characteristics of a new concept for the National Airspace System, or the new NAS, under which transportation goals such as increased throughput, delay reduction, and improved robustness could be realized. Since such an objective can be overwhelmingly complex if pursued at the lowest levels of detail, instead a System-of-Systems (SoS) approach was adopted to model alternative air transportation architectures at a high level. The SoS approach allows the consideration of not only the technical aspects of the NAS", but also incorporates policy, socio-economic, and alternative transportation system considerations into one architecture. While the representations of the individual systems are basic, the higher level approach allows for ways to optimize the SoS at the network level, determining the best topology (i.e. configuration of nodes and links). The final product (concept) is a set of rules of behavior and network structure that not only satisfies national transportation goals, but represents the high impact rules that accomplish those goals by getting the agents to "do the right thing" naturally. The novel combination of Agent Based Modeling and Network Theory provides the core analysis methodology in the System-of-Systems approach. Our method of approach is non-deterministic which means, fundamentally, it asks and answers different questions than deterministic models. The nondeterministic method is necessary primarily due to our marriage of human systems with technological ones in a partially unknown set of future worlds. Our goal is to understand and simulate how the SoS, human and technological components combined, evolve.

  6. Expression of apical Na(+)-L-glutamine co-transport activity, B(0)-system neutral amino acid co-transporter (B(0)AT1) and angiotensin-converting enzyme 2 along the jejunal crypt-villus axis in young pigs fed a liquid formula.

    PubMed

    Yang, Chengbo; Yang, Xiaojian; Lackeyram, Dale; Rideout, Todd C; Wang, Zirong; Stoll, Barbara; Yin, Yulong; Burrin, Douglas G; Fan, Ming Z

    2016-06-01

    Gut apical amino acid (AA) transport activity is high at birth and during suckling, thus being essential to maintain luminal nutrient-dependent mucosal growth through providing AA as essential metabolic fuel, substrates and nutrient stimuli for cellular growth. Because system-B(0) Na(+)-neutral AA co-transporter (B(0)AT1, encoded by the SLC6A19 gene) plays a dominant role for apical uptake of large neutral AA including L-Gln, we hypothesized that high apical Na(+)-Gln co-transport activity, and B(0)AT1 (SLC6A19) in co-expression with angiotensin-converting enzyme 2 (ACE2) were expressed along the entire small intestinal crypt-villus axis in young animals via unique control mechanisms. Kinetics of Na(+)-Gln co-transport activity in the apical membrane vesicles, prepared from epithelial cells sequentially isolated along the jejunal crypt-villus axis from liquid formula-fed young pigs, were measured with the membrane potential being clamped to zero using thiocyanate. Apical maximal Na(+)-Gln co-transport activity was much higher (p < 0.05) in the upper villus cells than in the middle villus (by 29 %) and the crypt (by 30 %) cells, whereas Na(+)-Gln co-transport affinity was lower (p < 0.05) in the upper villus cells than in the middle villus and the crypt cells. The B(0)AT1 (SLC6A19) mRNA abundance was lower (p < 0.05) in the crypt (by 40-47 %) than in the villus cells. There were no significant differences in B(0)AT1 and ACE2 protein abundances on the apical membrane among the upper villus, the middle villus and the crypt cells. Our study suggests that piglet fast growth is associated with very high intestinal apical Na(+)-neutral AA uptake activities via abundantly co-expressing B(0)AT1 and ACE2 proteins in the apical membrane and by transcribing the B(0)AT1 (SLC6A19) gene in the epithelia along the entire crypt-villus axis. PMID:26984322

  7. Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro

    PubMed Central

    Ono, Masahiro; Baden, Atsumi; Okudaira, Hiroyuki; Kobayashi, Masato; Kawai, Keiichi; Oka, Shuntaro; Yoshimura, Hirokatsu

    2016-01-01

    [18F]Fluciclovine (trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid; anti-[18F]FACBC), a positron emission tomography tracer used for the diagnosis of recurrent prostate cancer, is transported via amino acid transporters (AATs) with high affinity (Km: 97–230 μM). However, the mechanism underlying urinary excretion is unknown. In this study, we investigated the involvement of AATs and drug transporters in renal [18F]fluciclovine reuptake. [14C]Fluciclovine (trans-1-amino-3-fluoro[1-14C]cyclobutanecarboxylic acid) was used because of its long half-life. The involvement of AATs in [14C]fluciclovine transport was measured by apical-to-basal transport using an LLC-PK1 monolayer as model for renal proximal tubules. The contribution of drug transporters herein was assessed using vesicles/cells expressing the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance-associated protein 4 (MRP4), organic anion transporter 1 (OAT1), organic anion transporter 3 (OAT3) , organic cation transporter 2 (OCT2), organic anion transporting polypeptide 1B1 (OATP1B1), and organic anion transporting polypeptide 1B3 (OATP1B3). The apical-to-basal transport of [14C]fluciclovine was attenuated by l-threonine, the substrate for system alanine-serine-cysteine (ASC) AATs. [14C]Fluciclovine uptake by drug transporter-expressing vesicles/cells was not significantly different from that of control vesicles/cells. Fluciclovine inhibited P-gp, MRP4, OAT1, OCT2, and OATP1B1 (IC50 > 2.95 mM). Therefore, system ASC AATs may be partly involved in the renal reuptake of [18F]fluciclovine. Further, given that [18F]fluciclovine is recognized as an inhibitor with millimolar affinity for the tested drug transporters, slow urinary excretion of [18F]fluciclovine may be mediated by system ASC AATs, but not by drug transporters. PMID:27754421

  8. Induction of amino acid transporters expression by endurance exercise in rat skeletal muscle

    SciTech Connect

    Murakami, Taro Yoshinaga, Mariko

    2013-10-04

    Highlights: •Regulation of amino acid transporter expression in working muscle remains unclear. •Expression of amino acid transporters for leucine were induced by a bout of exercise. •Requirement of leucine in muscle cells might regulate expression of its transporters. •This information is beneficial for understanding the muscle remodeling by exercise. -- Abstract: We here investigated whether an acute bout of endurance exercise would induce the expression of amino acid transporters that regulate leucine transport across plasma and lysosomal membranes in rat skeletal muscle. Rats ran on a motor-driven treadmill at a speed of 28 m/min for 90 min. Immediately after the exercise, we observed that expression of mRNAs encoding L-type amino acid transporter 1 (LAT1) and CD98 was induced in the gastrocnemius, soleus, and extensor digitorum longus (EDL) muscles. Sodium-coupled neutral amino acid transporter 2 (SNAT2) mRNA was also induced by the exercise in those three muscles. Expression of proton-assisted amino acid transporter 1 (PAT1) mRNA was slightly but not significantly induced by a single bout of exercise in soleus and EDL muscles. Exercise-induced mRNA expression of these amino acid transporters appeared to be attenuated by repeated bouts of the exercise. These results suggested that the expression of amino acid transporters for leucine may be induced in response to an increase in the requirement for this amino acid in the cells of working skeletal muscles.

  9. Bacterial ferrous iron transport: the Feo system.

    PubMed

    Lau, Cheryl K Y; Krewulak, Karla D; Vogel, Hans J

    2016-03-01

    To maintain iron homeostasis within the cell, bacteria have evolved various types of iron acquisition systems. Ferric iron (Fe(3+)) is the dominant species in an oxygenated environment, while ferrous iron (Fe(2+)) is more abundant under anaerobic conditions or at low pH. For organisms that must combat oxygen limitation for their everyday survival, pathways for the uptake of ferrous iron are essential. Several bacterial ferrous iron transport systems have been described; however, only the Feo system appears to be widely distributed and is exclusively dedicated to the transport of iron. In recent years, many studies have explored the role of the FeoB and FeoA proteins in ferrous iron transport and their contribution toward bacterial virulence. The three-dimensional structures for the Feo proteins have recently been determined and provide insight into the molecular details of the transport system. A highly select group of bacteria also express the FeoC protein from the same operon. This review will provide a comprehensive look at the structural and functional aspects of the Feo system. In addition, bioinformatics analyses of the feo operon and the Feo proteins have been performed to complement our understanding of this ubiquitous bacterial uptake system, providing a new outlook for future studies.

  10. Electrical Transport Properties of Au-Doped Deoxyribonucleic Acid Molecules

    NASA Astrophysics Data System (ADS)

    Hwang, Jong Seung; Hong, Su Heon; Kim, Hyung Kwon; Kwon, Young Whan; Jin, Jung Il; Hwang, Sung Woo; Ahn, Doyeol

    2005-04-01

    Deoxyribonucleic acid (DNA) molecules were doped with Au atoms and their electrical transport properties were measured. The Au doping was carried out by incubating a mixture of HAuCl4\\cdot3H2O and DNA solutions. The binding of Au atoms to DNA bases was identified using Fourier transform infrared spectroscopy and X-ray photoemission spectroscopy. The Au-doped DNA molecules were deposited on nanoelectrodes and the presence of the molecules between the electrodes was determined by both scanning electron microscopy and atomic force microscopy. Measurement of the current-voltage characteristics showed that the Au-doped DNA molecules exhibited a higher conductivity than undoped DNA molecules. Detailed analysis of the chemical composition shows that there is a strong possibility of reliably controlling the conductivity of DNA molecules using this method.

  11. Acoustic system for material transport

    NASA Technical Reports Server (NTRS)

    Barmatz, M. B.; Trinh, E. H.; Wang, T. G.; Elleman, D. D.; Jacobi, N. (Inventor)

    1983-01-01

    An object within a chamber is acoustically moved by applying wavelengths of different modes to the chamber to move the object between pressure wells formed by the modes. In one system, the object is placed in one end of the chamber while a resonant mode, applied along the length of the chamber, produces a pressure well at the location. The frequency is then switched to a second mode that produces a pressure well at the center of the chamber, to draw the object. When the object reaches the second pressure well and is still traveling towards the second end of the chamber, the acoustic frequency is again shifted to a third mode (which may equal the first model) that has a pressure well in the second end portion of the chamber, to draw the object. A heat source may be located near the second end of the chamber to heat the sample, and after the sample is heated it can be cooled by moving it in a corresponding manner back to the first end of the chamber. The transducers for levitating and moving the object may be all located at the cool first end of the chamber.

  12. The Secure, Transportable, Autonomous Reactor System

    SciTech Connect

    Brown, N.W.; Hassberger, J.A.; Smith, C.; Carelli, M.; Greenspan, E.; Peddicord, K.L.; Stroh, K.; Wade, D.C.; Hill, R.N.

    1999-05-27

    The Secure, Transportable, Autonomous Reactor (STAR) system is a development architecture for implementing a small nuclear power system, specifically aimed at meeting the growing energy needs of much of the developing world. It simultaneously provides very high standards for safety, proliferation resistance, ease and economy of installation, operation, and ultimate disposition. The STAR system accomplishes these objectives through a combination of modular design, factory manufacture, long lifetime without refueling, autonomous control, and high reliability.

  13. Peroxisomal beta-oxidation of branched chain fatty acids in rat liver. Evidence that carnitine palmitoyltransferase I prevents transport of branched chain fatty acids into mitochondria.

    PubMed

    Singh, H; Beckman, K; Poulos, A

    1994-04-01

    Fatty acid beta-oxidation was investigated in highly purified mitochondrial and peroxisomal preparations from rat liver. Under isotonic conditions, pristanic and homophytanic acid beta-oxidation in purified peroxisomes was severalfold greater compared to the oxidation in purified mitochondria. Branched chain fatty acid beta-oxidation in purified mitochondria was very low, and the oxidation was not stimulated by exogenous L-carnitine or L-malate. In contrast, stearic acid beta-oxidation by purified mitochondria depended upon exogenous L-carnitine, and the oxidation was stimulated by L-malate. Both mitochondrial and peroxisomal beta-oxidation of branched chain fatty acids was strongly inhibited by fatty acid-free bovine serum albumin, whereas stearic acid oxidation was either unaffected or slightly inhibited by bovine serum albumin. The results presented clearly indicate that branched chain fatty acids are mainly degraded in peroxisomes in rat liver. Branched chain fatty acids were efficiently converted to coenzyme A thioesters by purified mitochondria, peroxisomes, and microsomes. Although pristanic and phytanic acids were rapidly converted to pristanoyl-CoA and phytanoyl-CoA, respectively, they were not converted to carnitine esters by mitochondrial outer membranes. The results indicate that acyl-CoA synthetase and carnitine acyltransferase located at the mitochondrial outer membranes regulate entry of branched chain fatty acids into mitochondria. Mitochondrial carnitine acyltransferase I appears to be highly specific for straight chain fatty acids and restricts entry of branched chain fatty acids into mitochondria. Thus, branched chain fatty acids which cannot be transported across the mitochondrial membranes via the carnitine acyltransferase system are directed to peroxisomes for beta-oxidation. The results reported indicate that phytanic acid, the fatty acid which can be initially degraded by alpha-oxidation due to the presence of a beta-methyl group in the

  14. A Mars/phobos Transportation System

    NASA Technical Reports Server (NTRS)

    1989-01-01

    A transportation system will be necessary to support construction and operation of bases on Phobos and Mars beginning in the year 2020 or later. An approach to defining a network of vehicles and the types of vehicles which may be used in the system are presented. The network will provide a convenient, integrated means for transporting robotically constructed bases to Phobos and Mars. All the technology needed for the current plan is expected to be available for use at the projected date of cargo departure from the Earth system. The modular design of the transportation system provides easily implemented contingency plans, so that difficulties with any one vehicle will have a minimal effect on the progress of the total mission. The transportation network proposed consists of orbital vehicles and atmospheric entry vehicles. Initially, only orbital vehicles will participate in the robotic construction phase of the Phobos base. The Interplanetary Transfer Vehicle (ITV) will carry the base and construction equipment to Phobos where the Orbital Maneuvering Vehicles (OMV's) will participate in the initial construction of the base. When the Mars base is ready to be sent, one or more ITV's will be used to transport the atmospheric entry vehicles from Earth. These atmospheric vehicles are the One Way Landers (OWL's) and the Ascent/Descent Vehicles (ADV's). They will be used to carry the base components and/or construction equipment. The OMV's and the Orbital Transfer Vehicles (OTV's) will assist in carrying the atmospheric entry vehicles to low Martian orbit where the OWL's or ADV's will descent to the planet surface. The ADV's were proposed to accommodate expansion of the system. Additionally, a smaller version of the ADV class is capable of transporting personnel between Mars and Phobos.

  15. Acid-base transport by the renal proximal tubule

    PubMed Central

    Skelton, Lara A.; Boron, Walter F.; Zhou, Yuehan

    2015-01-01

    Each day, the kidneys filter 180 L of blood plasma, equating to some 4,300 mmol of the major blood buffer, bicarbonate (HCO3−). The glomerular filtrate enters the lumen of the proximal tubule (PT), and the majority of filtered HCO3− is reclaimed along the early (S1) and convoluted (S2) portions of the PT in a manner coupled to the secretion of H+ into the lumen. The PT also uses the secreted H+ to titrate non-HCO3− buffers in the lumen, in the process creating “new HCO3−” for transport into the blood. Thus, the PT – along with more distal renal segments – is largely responsible for regulating plasma [HCO3−]. In this review we first focus on the milestone discoveries over the past 50+ years that define the mechanism and regulation of acid-base transport by the proximal tubule. Further on in the review, we will summarize research still in progress from our laboratory, work that addresses the problem of how the PT is able to finely adapt to acid–base disturbances by rapidly sensing changes in basolateral levels of HCO3− and CO2 (but not pH), and thereby to exert tight control over the acid–base composition of the blood plasma. PMID:21170887

  16. Transportation systems analyses. Volume 1: Executive summary

    NASA Astrophysics Data System (ADS)

    1992-11-01

    The principal objective is to accomplish a systems engineering assessment of the nation's space transportation infrastructure. This analysis addresses the necessary elements to perform crew delivery and return, cargo transfer, cargo delivery and return, payload servicing, and the exploration of the Moon and Mars. Specific elements analyzed, but not limited to, include: the Space Exploration Initiative (SEI), the National Launch System (NLS), the current expendable launch vehicle (ELV) fleet, ground facilities, the Space Station Freedom (SSF), and other civil, military and commercial payloads. The performance of this study entails maintaining a broad perspective on the large number of transportation elements that could potentially comprise the U.S. space infrastructure over the next several decades. To perform this systems evaluation, top-level trade studies are conducted to enhance our understanding of the relationship between elements of the infrastructure. This broad 'infrastructure-level perspective' permits the identification of preferred infrastructures. Sensitivity analyses are performed to assure the credibility and usefulness of study results. Conceptual studies of transportation elements contribute to the systems approach by identifying elements (such as ETO node and transfer/excursion vehicles) needed in current and planned transportation systems. These studies are also a mechanism to integrate the results of relevant parallel studies.

  17. Crew Transportation System Design Reference Missions

    NASA Technical Reports Server (NTRS)

    Mango, Edward J.

    2015-01-01

    Contains summaries of potential design reference mission goals for systems to transport humans to andfrom low Earth orbit (LEO) for the Commercial Crew Program. The purpose of this document is to describe Design Reference Missions (DRMs) representative of the end-to-end Crew Transportation System (CTS) framework envisioned to successfully execute commercial crew transportation to orbital destinations. The initial CTS architecture will likely be optimized to support NASA crew and NASA-sponsored crew rotation missions to the ISS, but consideration may be given in this design phase to allow for modifications in order to accomplish other commercial missions in the future. With the exception of NASA’s mission to the ISS, the remaining commercial DRMs are notional. Any decision to design or scar the CTS for these additional non-NASA missions is completely up to the Commercial Provider. As NASA’s mission needs evolve over time, this document will be periodically updated to reflect those needs.

  18. Ion transport membrane module and vessel system

    DOEpatents

    Stein, VanEric Edward; Carolan, Michael Francis; Chen, Christopher M.; Armstrong, Phillip Andrew; Wahle, Harold W.; Ohrn, Theodore R.; Kneidel, Kurt E.; Rackers, Keith Gerard; Blake, James Erik; Nataraj, Shankar; van Doorn, Rene Hendrik Elias; Wilson, Merrill Anderson

    2007-02-20

    An ion transport membrane system comprising (a) a pressure vessel having an interior, an exterior, an inlet, and an outlet; (b) a plurality of planar ion transport membrane modules disposed in the interior of the pressure vessel and arranged in series, each membrane module comprising mixed metal oxide ceramic material and having an interior region and an exterior region, wherein any inlet and any outlet of the pressure vessel are in flow communication with exterior regions of the membrane modules; and (c) one or more gas manifolds in flow communication with interior regions of the membrane modules and with the exterior of the pressure vessel. The ion transport membrane system may be utilized in a gas separation device to recover oxygen from an oxygen-containing gas or as an oxidation reactor to oxidize compounds in a feed gas stream by oxygen permeated through the mixed metal oxide ceramic material of the membrane modules.

  19. Ion transport membrane module and vessel system

    DOEpatents

    Stein, VanEric Edward; Carolan, Michael Francis; Chen, Christopher M.; Armstrong, Phillip Andrew; Wahle, Harold W.; Ohrn, Theodore R.; Kneidel, Kurt E.; Rackers, Keith Gerard; Blake, James Erik; Nataraj, Shankar; van Doorn, Rene Hendrik Elias; Wilson, Merrill Anderson

    2008-02-26

    An ion transport membrane system comprising (a) a pressure vessel having an interior, an exterior, an inlet, and an outlet; (b) a plurality of planar ion transport membrane modules disposed in the interior of the pressure vessel and arranged in series, each membrane module comprising mixed metal oxide ceramic material and having an interior region and an exterior region, wherein any inlet and any outlet of the pressure vessel are in flow communication with exterior regions of the membrane modules; and (c) one or more gas manifolds in flow communication with interior regions of the membrane modules and with the exterior of the pressure vessel.The ion transport membrane system may be utilized in a gas separation device to recover oxygen from an oxygen-containing gas or as an oxidation reactor to oxidize compounds in a feed gas stream by oxygen permeated through the mixed metal oxide ceramic material of the membrane modules.

  20. Ion transport membrane module and vessel system

    DOEpatents

    Stein, VanEric Edward; Carolan, Michael Francis; Chen, Christopher M.; Armstrong, Phillip Andrew; Wahle, Harold W.; Ohrn, Theodore R.; Kneidel, Kurt E.; Rackers, Keith Gerard; Blake, James Erik; Nataraj, Shankar; Van Doorn, Rene Hendrik Elias; Wilson, Merrill Anderson

    2012-02-14

    An ion transport membrane system comprising (a) a pressure vessel having an interior, an exterior, an inlet, and an outlet; (b) a plurality of planar ion transport membrane modules disposed in the interior of the pressure vessel and arranged in series, each membrane module comprising mixed metal oxide ceramic material and having an interior region and an exterior region, wherein any inlet and any outlet of the pressure vessel are in flow communication with exterior regions of the membrane modules; and (c) one or more gas manifolds in flow communication with interior regions of the membrane modules and with the exterior of the pressure vessel. The ion transport membrane system may be utilized in a gas separation device to recover oxygen from an oxygen-containing gas or as an oxidation reactor to oxidize compounds in a feed gas stream by oxygen permeated through the mixed metal oxide ceramic material of the membrane modules.

  1. Low energy beam transport system developments

    NASA Astrophysics Data System (ADS)

    Dudnikov, V.; Han, B.; Stockli, M.; Welton, R.; Dudnikova, G.

    2015-04-01

    For high brightness beam production it is important to preserve the brightness in the low energy beam transport system (LEBT) used to transport and match the ion beams to the next stage of acceleration, usually an RFQ. While electrostatic focusing can be problematic for high current beam transport, reliable electrostatic LEBT operation has been demonstrated with H- beams up to 60 mA. Now, however, it is commonly accepted that an optimal LEBT for high current accelerator applications consists of focusing solenoids with space charge compensation. Two-solenoid LEBTs are successfully used for high current (>100 mA) proton beam transport. Preservation of low emittances (~0.15 π mm-mrad) requires the addition of a heavy gas (Xe, Kr), which causes ~5% of proton loss in a 1 m long LEBT. Similar Xe densities would be required to preserve low emittances of H- beams, but such gas densities cause unacceptably high H- beam losses. A short LEBT with only one short solenoid, movable for RFQ matching, can be used for reduced negative ion stripping. A strong electrostatic-focusing LEBT has been successfully adopted for transport of high current H- beams in the SNS Front End. Some modifications of such electrostatic LEBTs are expected to improve the reliable transport of intense positive and negative ion beams without greatly degrading their low emittances. We concentrate on processes that determine the beam brightness degradation and on their prevention. Proposed improvements to the SNS electrostatic LEBT are discussed.

  2. The role of transport processes in survival of lactic acid bacteria. Energy transduction and multidrug resistance.

    PubMed

    Konings, W N; Lolkema, J S; Bolhuis, H; van Veen, H W; Poolman, B; Driessen, A J

    1997-02-01

    Lactic acid bacteria play an essential role in many food fermentation processes. They are anaerobic organisms which obtain their metabolic energy by substrate phosphorylation. In addition three secondary energy transducing processes can contribute to the generation of a proton motive force: proton/substrate symport as in lactic acid excretion, electrogenic precursor/product exchange as in malolactic and citrolactic fermentation and histidine/histamine exchange, and electrogenic uniport as in malate and citrate uptake in Leuconostoc oenos. In several of these processes additional H+ consumption occurs during metabolism leading to the generation of a pH gradient, internally alkaline. Lactic acid bacteria have also developed multidrug resistance systems. In Lactococcus lactis three toxin excretion systems have been characterized: cationic toxins can be excreted by a toxin/proton antiport system and by an ABC-transporter. This cationic ABC-transporter has surprisingly high structural and functional analogy with the human MDR1-(P-glycoprotein). For anions an ATP-driven ABC-like excretion systems exist.

  3. Heat transport system, method and material

    DOEpatents

    Musinski, Donald L.

    1987-01-01

    A heat transport system, method and composite material in which a plurality of hollow spherical shells or microspheres having an outside diameter of less than or equal to 500 microns are encapsulated or embedded within a bulk material. Each shell has captured therein a volatile working fluid, such that each shell operates as a microsized heat pipe for conducting heat through the composite structure.

  4. Transportation systems analyses: Volume 1: Executive Summary

    NASA Astrophysics Data System (ADS)

    1993-05-01

    The principal objective of this study is to accomplish a systems engineering assessment of the nation's space transportation infrastructure. This analysis addresses the necessary elements to perform man delivery and return, cargo transfer, cargo delivery, payload servicing, and the exploration of the Moon and Mars. Specific elements analyzed, but not limited to, include the Space Exploration Initiative (SEI), the National Launch System (NLS), the current expendable launch vehicle (ELV) fleet, ground facilities, the Space Station Freedom (SSF), and other civil, military and commercial payloads. The performance of this study entails maintaining a broad perspective on the large number of transportation elements that could potentially comprise the U.S. space infrastructure over the next several decades. To perform this systems evaluation, top-level trade studies are conducted to enhance our understanding of the relationships between elements of the infrastructure. This broad 'infrastructure-level perspective' permits the identification of preferred infrastructures. Sensitivity analyses are performed to assure the credibility and usefulness of study results. This executive summary of the transportation systems analyses (TSM) semi-annual report addresses the SSF logistics resupply. Our analysis parallels the ongoing NASA SSF redesign effort. Therefore, there could be no SSF design to drive our logistics analysis. Consequently, the analysis attempted to bound the reasonable SSF design possibilities (and the subsequent transportation implications). No other strategy really exists until after a final decision is rendered on the SSF configuration.

  5. The D-amino acid transport by the invertebrate SLC6 transporters KAAT1 and CAATCH1 from Manduca sexta.

    PubMed

    Vollero, Alessandra; Imperiali, Francesca G; Cinquetti, Raffaella; Margheritis, Eleonora; Peres, Antonio; Bossi, Elena

    2016-02-01

    The ability of the SLC6 family members, the insect neutral amino acid cotransporter KAAT1(K(+)-coupled amino acid transporter 1) and its homologous CAATCH1(cation anion activated amino acid transporter/channel), to transport D-amino acids has been investigated through heterologous expression in Xenopus laevis oocytes and electrophysiological techniques. In the presence of D-isomers of leucine, serine, and proline, the msKAAT1 generates inward, transport-associated, currents with variable relative potencies, depending on the driving ion Na(+) or K(+). Higher concentrations of D-leucine (≥1 mmol/L) give rise to an anomalous response that suggests the existence of a second binding site with inhibitory action on the transport process. msCAATCH1 is also able to transport the D-amino acids tested, including D-leucine, whereas L-leucine acts as a blocker. A similar behavior is exhibited by the KAAT1 mutant S308T, confirming the relevance of the residue in this position in L-leucine binding and the different interaction of D-leucine with residues involved in transport mechanism. D-leucine and D-serine on various vertebrate orthologs B(0)AT1 (SLC6A19) elicited only a very small current and singular behavior was not observed, indicating that it is specific of the insect neutral amino acid transporters. These findings highlight the relevance of D-amino acid absorption in the insect nutrition and metabolism and may provide new evidences in the molecular transport mechanism of SLC6 family. PMID:26884475

  6. Future space transportation systems analysis study. Phase 1 extension: Transportation systems reference data, volume 2

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Transportation mass requirements are developed for various mission and transportation modes based on vehicle systems sized to fit the exact needs of each mission. The parametric data used to derive the mass requirements for each mission and transportation mode are presented to enable accommodation of possible changes in mode options or payload definitions. The vehicle sizing and functional requirements used to derive the parametric data are described.

  7. Evaluating remedial alternatives for an acid mine drainage stream: Application of a reactive transport model

    USGS Publications Warehouse

    Runkel, R.L.; Kimball, B.A.

    2002-01-01

    A reactive transport model based on one-dimensional transport and equilibrium chemistry is applied to synoptic data from an acid mine drainage stream. Model inputs include streamflow estimates based on tracer dilution, inflow chemistry based on synoptic sampling, and equilibrium constants describing acid/base, complexation, precipitation/dissolution, and sorption reactions. The dominant features of observed spatial profiles in pH and metal concentration are reproduced along the 3.5-km study reach by simulating the precipitation of Fe(III) and Al solid phases and the sorption of Cu, As, and Pb onto freshly precipitated iron-(III) oxides. Given this quantitative description of existing conditions, additional simulations are conducted to estimate the streamwater quality that could result from two hypothetical remediation plans. Both remediation plans involve the addition of CaCO3 to raise the pH of a small, acidic inflow from ???2.4 to ???7.0. This pH increase results in a reduced metal load that is routed downstream by the reactive transport model, thereby providing an estimate of post-remediation water quality. The first remediation plan assumes a closed system wherein inflow Fe(II) is not oxidized by the treatment system; under the second remediation plan, an open system is assumed, and Fe(II) is oxidized within the treatment system. Both plans increase instream pH and substantially reduce total and dissolved concentrations of Al, As, Cu, and Fe(II+III) at the terminus of the study reach. Dissolved Pb concentrations are reduced by ???18% under the first remediation plan due to sorption onto iron-(III) oxides within the treatment system and stream channel. In contrast, iron(III) oxides are limiting under the second remediation plan, and removal of dissolved Pb occurs primarily within the treatment system. This limitation results in an increase in dissolved Pb concentrations over existing conditions as additional downstream sources of Pb are not attenuated by

  8. Space Transportation System (STS): Emergency support

    NASA Technical Reports Server (NTRS)

    Janoski, T.; Nicholson, L.

    1991-01-01

    The DSN (Deep Space Network) mission support requirements for emergency support of the Space Transportation System (STS) are summarized. Coverage would be provided by the DSN during emergencies that would prevent communications between the shuttle and the White Sands TDRSS receiving station. The DSN support requirements are defined through the presentation of tables and narratives describing the spacecraft flight profile; DSN support coverage; frequency assignments; support parameters for telemetry, command and support systems; and tracking support responsibility.

  9. Fireworthiness of transport aircraft interior systems

    NASA Technical Reports Server (NTRS)

    Parker, J. A.; Kourtides, D. A.

    1982-01-01

    The fire worthiness of air transport interiors was evaluated. The effect of interior systems on the survival of passengers and crew in an uncontrolled transport aircraft fire is addressed. Modification of aircraft interior subsystem components which provide improvements in aircraft fire safety are examined. Three specific subsystem components, interior panels, seats and windows, offer the most immediate and highest payoff by modifying interior materials of existing aircrafts. It is shown that the new materials modifications reduce the fire hazards because of significant reduction in their characteristic flame spread, heat release, and smoke and toxic gas emissions.

  10. Intestinal transport of zinc and folic acid: a mutual inhibitory effect

    SciTech Connect

    Ghishan, F.K.; Said, H.M.; Wilson, P.C.; Murrell, J.E.; Greene, H.L.

    1986-02-01

    Recent observations suggest an inverse relationship between folic acid intake and zinc nutriture and indicate an interaction between folic acid and zinc at the intestinal level. To define that interaction, we designed in vivo and in vitro transport studies in which folic acid transport in the presence of zinc, as well as zinc transport in the presence of folic acid was examined. These studies show that zinc transport is significantly decreased when folate is present in the intestinal lumen. Similarly folic acid transport is significantly decreased with the presence of zinc. To determine whether this intestinal inhibition is secondary to zinc and folate-forming complexes, charcoal-binding studies were performed. These studies indicate that zinc and folate from complexes at pH 2.0, but that at pH 6.0, these complexes dissolve. Therefore, our studies suggest that under normal physiological conditions a mutual inhibition between folate and zinc exists at the site of intestinal transport.

  11. Amyloid protein precursor stimulates excitatory amino acid transport. Implications for roles in neuroprotection and pathogenesis.

    PubMed

    Masliah, E; Raber, J; Alford, M; Mallory, M; Mattson, M P; Yang, D; Wong, D; Mucke, L

    1998-05-15

    Excitatory neurotransmitters such as glutamate are required for the normal functioning of the central nervous system but can trigger excitotoxic neuronal injury if allowed to accumulate to abnormally high levels. Their extracellular levels are controlled primarily by transmitter uptake into astrocytes. Here, we demonstrate that the amyloid protein precursor may participate in the regulation of this important process. The amyloid protein precursor has been well conserved through evolution, and a number of studies indicate that it may function as an endogenous excitoprotectant. However, the mechanisms underlying this neuroprotective capacity remain largely unknown. At moderate levels of expression, human amyloid protein precursors increased glutamate/aspartate uptake in brains of transgenic mice, with the 751-amino acid isoform showing greater potency than the 695-amino acid isoform. Cerebral glutamate/aspartate transporter protein levels were higher in transgenic mice than in non-transgenic controls, whereas transporter mRNA levels were unchanged. Amyloid protein precursor-dependent stimulation of aspartate uptake by cultured primary astrocytes was associated with increases in protein kinase A and C activity and could be blocked by inhibitors of these kinases. The stimulation of astroglial excitatory amino acid transport by amyloid protein precursors could protect the brain against excitotoxicity and may play an important role in neurotransmission. PMID:9575214

  12. A Course in Transport Phenomena in Multicomponent, Multiphase, Reacting Systems.

    ERIC Educational Resources Information Center

    Carbonell, R. G.; Whitaker, S.

    1978-01-01

    This course concentrates on a rigorous development of the multicomponent transport equations, boundary conditions at phase interfaces, and volume-averaged transport equations for multiphase reacting systems. (BB)

  13. The Palm Desert Renewable Hydrogen Transportation System

    SciTech Connect

    Lehman, P.

    1996-10-01

    The present paper describes, for purposes of the Department of Energy (DoE) Hydrogen Program Review, Schatz Energy Research Center (SERC) progress on the Palm Desert Renewable Hydrogen Transportation System Project for the period January through June 1996. This period represents the first six months of the three year project. The estimated cost over three years is $3.9M, $1.859M of which is funded by the DoE ($600 k for fiscal year 1996). The goal of the Palm Desert Project is to develop a clean and sustainable transportation system for a community. The project will demonstrate the practical utility of hydrogen as a transportation fuel and proton exchange membrane (PEM) fuel cells as vehicle power plants. This transportation system will be developed in the City of Palm Desert in southern California and will include a fleet of 8 fuel cell powered vehicles, solar and wind powered hydrogen generating facilities, a consumer-ready refueling station, and a service infrastructure. The system holds the promise of a clean environment and an energy supply that is predictable, domestic, safe, and abundant. During, the first part of 1996 SERC has nearly completed building a fuel cell powered personal utility vehicle, which features an upgraded safety and computer system; they have designed and built a test bench that is able to mimic golf cart loads and test fuel cell system auxiliary components; they have begun the design of the solar hydrogen generating station; they have worked with Sandia National Laboratory on an advanced metal hydride storage system; they have increased the power density of the SERC fuel cell by as much as 50%; and they have reached out to the rest of the world with a new fact sheet, world wide web pages, a press release, video footage for a television program. and instruction within the community.

  14. Liners for ion transport membrane systems

    SciTech Connect

    Carolan, Michael Francis; Miller, Christopher Francis

    2010-08-10

    Ion transport membrane system comprising (a) a pressure vessel comprising an interior, an exterior, an inlet, an inlet conduit, an outlet, and an outlet conduit; (b) a plurality of planar ion transport membrane modules disposed in the interior of the pressure vessel and arranged in series, each membrane module comprising mixed metal oxide ceramic material and having an interior region and an exterior region, wherein the inlet and the outlet of the pressure vessel are in flow communication with exterior regions of the membrane modules; (c) a gas manifold having an interior surface wherein the gas manifold is in flow communication with the interior region of each of the planar ion transport membrane modules and with the exterior of the pressure vessel; and (d) a liner disposed within any of the inlet conduit, the outlet conduit, and the interior surface of the gas manifold.

  15. Thermal protection systems for hypersonic transport vehicles

    NASA Astrophysics Data System (ADS)

    Reich, G.; Hinger, J.; Huchler, M.

    1990-07-01

    Thermal protection systems (TPS) for hypersonic transport vehicles are described and evaluated. During the flight through the atmosphere moderate to high aerodynamic heating rates with corresponding high surface temperatures are generated. Therefore, a reliable light-weight but effective TPS is required, that limits the heat transfer into the central fuselage with the liquid hydrogen tank and that prevents the penetration of the temperature peak during stage separation to the load carrying structure. The heat transfer modes in the insulation are solid conduction, gas convection and radiation. Thermal protection systems based on different phenomena to reduce the heat transfer, like vacuum shingles, inert gas filled shingles, microporous insulations and multiwall structures, are described. It is demonstrated that microporous and multiwall insulations are efficient, light weight and reliable TPSs for future hypersonic transportation systems.

  16. DTS: The NOAO Data Transport System

    NASA Astrophysics Data System (ADS)

    Fitzpatrick, M.; Semple, T.

    2014-05-01

    The NOAO Data Transport System (DTS) provides high-throughput, reliable, data transfer between telescopes, pipelines and archive centers located in the Northern and Southern hemispheres. It is a distributed application using XML-RPC for command and control, and either parallel-TCP or UDT protocols for bulk data transport. The system is data-agnostic, allowing arbitrary files or directories to be moved using the same infrastructure. Data paths are configurable in the system by connecting nodes as the source or destination of data in a queue. Each leg of a data path may be configured independently based on the network environment between the sites. A queueing model is currently implemented to manage the automatic movement of data, a streaming model is planned to support arbitrarily large transfers (e.g. as in a disk recovery scenario) or to provide a 'pass-thru' interface to minize overheads. A web-based monitor allows anyone to get a graphical overview of the DTS system as it runs, operators will be able to control individual nodes in the system. Through careful tuning of the network paths DTS is able to achieve in excess of 80-percent of the nominal wire speed using only commodity networks, making it ideal for long-haul transport of large volumes of data.

  17. Charged Amino Acids (R83, E567, D617, E625, R669, and K678) of CusA Are Required for Metal Ion Transport in the Cus Efflux System

    SciTech Connect

    Su, Chih-Chia; Long, Feng; Lei, Hsiang-Ting; Reddy Bolla, Jani; Do, Sylvia V.; Rajashankar, Kanagalaghatta R.; Yu, Edward W.

    2012-10-23

    Gram-negative bacteria expel various toxic chemicals via tripartite efflux pumps belonging to the resistance-nodulation-cell division superfamily. These pumps span both the inner and outer membranes of the cell. The three components of these tripartite systems are an inner-membrane, substrate-binding transporter (or pump); a periplasmic membrane fusion protein (or adaptor); and an outer-membrane-anchored channel. These three efflux proteins interact in the periplasmic space to form the three-part complexes. We previously presented the crystal structures of both the inner-membrane transporter CusA and membrane fusion protein CusB of the CusCBA tripartite efflux system from Escherichia coli. We also described the co-crystal structure of the CusBA adaptor-transporter, revealing that the trimeric CusA efflux pump assembles with six CusB protein molecules to form the complex CusB{sub 6}-CusA{sub 3}. We here report three different conformers of the crystal structures of CusBA-Cu(I), suggesting a mechanism on how Cu(I) binding initiates a sequence of conformational transitions in the transport cycle. Genetic analysis and transport assays indicate that charged residues, in addition to the methionine pairs and clusters, are essential for extruding metal ions out of the cell.

  18. Release of salicylic acid, diclofenac acid and diclofenac acid salts from isotropic and anisotropic nonionic surfactant systems across rat skin.

    PubMed

    Gabboun, N H; Najib, N M; Ibrahim, H G; Assaf, S

    2001-01-01

    Release of salicylic acid, diclofenac acid, diclofenac diethylamine and diclofenac sodium, from lyotropic structured systems, namely; neat and middle liquid crystalline phases, across mid-dorsal hairless rat skin into aqueous buffer were studied. Release results were compared with those from the isotropic systems. The donor systems composed of the surfactant polyoxyethylene (20) isohexadecyl ether, HCl buffer of pH 1 or distilled water and the specific drug. High performance liquid chromatography (HPLC) methods were used to monitor the transfer of the drugs across the skin barrier. Results indicated that the rate-determining step in the transport process was the release of the drug from the specified donor system. Further, apparent zero order release was demonstrated with all systems. Except for diclofenac sodium, drug fluxes decreased as the donor medium changed from isotropic to anisotropic. The decrease in fluxes was probably due to the added constrains on the movement of drug molecules. By changing the anisotropic donor medium from neat to middle phase, drug flux decreased in case of salicylic acid and diclofenac sodium. In the mean time, flux increased in case of the diethylamine salt and appeared nearly similar in case of diclofenac acid. Rates of drug transfer across the skin from the anisotropic donors seemed to be largely controlled by the entropy contribution to the transport process. The type and extent of drug-liquid crystal interactions probably influenced the latter.

  19. Automatic braking system modification for the Advanced Transport Operating Systems (ATOPS) Transportation Systems Research Vehicle (TSRV)

    NASA Technical Reports Server (NTRS)

    Coogan, J. J.

    1986-01-01

    Modifications were designed for the B-737-100 Research Aircraft autobrake system hardware of the Advanced Transport Operating Systems (ATOPS) Program at Langley Research Center. These modifications will allow the on-board flight control computer to control the aircraft deceleration after landing to a continuously variable level for the purpose of executing automatic high speed turn-offs from the runway. A bread board version of the proposed modifications was built and tested in simulated stopping conditions. Test results, for various aircraft weights, turnoff speed, winds, and runway conditions show that the turnoff speeds are achieved generally with errors less than 1 ft/sec.

  20. Interaction of α-Lipoic Acid with the Human Na+/Multivitamin Transporter (hSMVT)*

    PubMed Central

    Zehnpfennig, Britta; Wiriyasermkul, Pattama; Carlson, David A.; Quick, Matthias

    2015-01-01

    The human Na+/multivitamin transporter (hSMVT) has been suggested to transport α-lipoic acid (LA), a potent antioxidant and anti-inflammatory agent used in therapeutic applications, e.g. in the treatment of diabetic neuropathy and Alzheimer disease. However, the molecular basis of the cellular delivery of LA and in particular the stereospecificity of the transport process are not well understood. Here, we expressed recombinant hSMVT in Pichia pastoris and used affinity chromatography to purify the detergent-solubilized protein followed by reconstitution of hSMVT in lipid bilayers. Using a combined approach encompassing radiolabeled LA transport and equilibrium binding studies in conjunction with the stabilized R-(+)- and S-(−)-enantiomers and the R,S-(+/−) racemic mixture of LA or lipoamide, we identified the biologically active form of LA, R-LA, to be the physiological substrate of hSMVT. Interaction of R-LA with hSMVT is strictly dependent on Na+. Under equilibrium conditions, hSMVT can simultaneously bind ∼2 molecules of R-LA in a biphasic binding isotherm with dissociation constants (Kd) of 0.9 and 7.4 μm. Transport of R-LA in the oocyte and reconstituted system is exclusively dependent on Na+ and exhibits an affinity of ∼3 μm. Measuring transport with known amounts of protein in proteoliposomes containing hSMVT in outside-out orientation yielded a catalytic turnover number (kcat) of about 1 s−1, a value that is well in agreement with other Na+-coupled transporters. Our data suggest that hSMVT-mediated transport is highly specific for R-LA at our tested concentration range, a finding with wide ramifications for the use of LA in therapeutic applications. PMID:25971966

  1. Small Aircraft Transportation System Concept and Technologies

    NASA Technical Reports Server (NTRS)

    Holmes, Bruce J.; Durham, Michael H.; Tarry, Scott E.

    2005-01-01

    This paper summarizes both the vision and the early public-private collaborative research for the Small Aircraft Transportation System (SATS). The paper outlines an operational definition of SATS, describes how SATS conceptually differs from current air transportation capabilities, introduces four SATS operating capabilities, and explains the relation between the SATS operating capabilities and the potential for expanded air mobility. The SATS technology roadmap encompasses on-demand, widely distributed, point-to-point air mobility, through hired-pilot modes in the nearer-term, and through self-operated user modes in the farther-term. The nearer-term concept is based on aircraft and airspace technologies being developed to make the use of smaller, more widely distributed community reliever and general aviation airports and their runways more useful in more weather conditions, in commercial hired-pilot service modes. The farther-term vision is based on technical concepts that could be developed to simplify or automate many of the operational functions in the aircraft and the airspace for meeting future public transportation needs, in personally operated modes. NASA technology strategies form a roadmap between the nearer-term concept and the farther-term vision. This paper outlines a roadmap for scalable, on-demand, distributed air mobility technologies for vehicle and airspace systems. The audiences for the paper include General Aviation manufacturers, small aircraft transportation service providers, the flight training industry, airport and transportation authorities at the Federal, state and local levels, and organizations involved in planning for future National Airspace System advancements.

  2. Reduced placental amino acid transport in response to maternal nutrient restriction in the baboon.

    PubMed

    Pantham, Priyadarshini; Rosario, Fredrick J; Nijland, Mark; Cheung, Alex; Nathanielsz, Peter W; Powell, Theresa L; Galan, Henry L; Li, Cun; Jansson, Thomas

    2015-10-01

    Intrauterine growth restriction increases the risk of perinatal complications and predisposes the infant to diabetes and cardiovascular disease in later life. Mechanisms by which maternal nutrient restriction (MNR) reduces fetal growth are poorly understood. We hypothesized that MNR decreases placental amino acid (AA) transporter activity, leading to reduced transplacental transfer of AAs. Pregnant baboons were fed either a control (ad libitum, n = 7), or MNR diet (70% of control diet, n = 7) from gestational day (GD) 30. At GD 165 (0.9 gestation), placentas (n = 7 in each group) were collected, and microvillous plasma membrane vesicles (MVM) isolated. MVM system A and system L AA transport was determined in vitro using radiolabeled substrates and rapid filtration techniques. In vivo transplacental AA transport was assessed by infusing nine (13)C- or (2)H-labeled essential AA as a bolus into the maternal circulation (n = 5 control, n = 4 MNR) at cesarean section. A fetal vein-to-maternal artery mole percent excess ratio for each essential AA was calculated. Fetal and placental weights were significantly reduced in the MNR group compared with controls (P < 0.01). The activity of system A and system L was markedly reduced by 73 and 84%, respectively, in MVM isolated from baboon placentas at GD 165 following MNR (P < 0.01). In vivo, the fetal vein-to-maternal artery mole percent excess ratio was significantly reduced for leucine, isoleucine, methionine, phenylalanine, threonine, and tryptophan in MNR baboons (P < 0.05). This is the first study to investigate placental AA transport in a nonhuman primate model of MNR. We demonstrate that the downregulation of system A and system L activity in syncytiotrophoblast MVM in MNR leads to decreased transplacental AA transport and, consequently, reduced circulating fetal AA concentrations, a potential mechanism linking maternal undernutrition to reduced fetal growth.

  3. Relative Rates of Amino Acid Import via the ABC Transporter GlnPQ Determine the Growth Performance of Lactococcus lactis

    PubMed Central

    Fulyani, Faizah; Schuurman-Wolters, Gea K.; Slotboom, Dirk-Jan

    2015-01-01

    ABSTRACT The GlnPQ transporter from Lactococcus lactis has the remarkable feature of having two substrate-binding domains (SBDs) fused to the N terminus of the transmembrane domain (TMD), and thus four SBDs are present in the homodimeric complex. Although X-ray structures and ligand binding data are available for both SBDs, little is known of how different amino acids compete with each other for transport via GlnPQ. Here we show GlnPQ has a broader substrate specificity than previously thought, with the ability to take up asparagine, glutamine, and glutamic acid, albeit via different routes and with different affinities. Asparagine and glutamine compete with each other at the level of binding to SBD1 and SBD2 (with differences in dissociation constant), but at the same time SBD1 and SBD2 compete with each other at the level of interaction with the translocator domain (with differences in affinity constant and rate of transport). Although glutamine transport via SBD1 is outcompeted by physiological concentrations of asparagine, SBD2 ensures high rates of import of the essential amino acid glutamine. Taken together, this study demonstrates that even in the presence of competing asparagine concentrations, GlnPQ has a high capacity to transport glutamine, which matches the high needs of the cell for glutamine and glutamate. IMPORTANCE GlnPQ is an ATP-binding cassette (ABC) transporter for glutamine, glutamic acid, and asparagine. The system is essential in various Gram-positive bacteria, including L. lactis and several pathogens. Here we show how the amino acids compete with each other for binding to the multiple SBDs of GlnPQ and how these SBDs compete with each other for substrate delivery to the transporter. Overall, our results show that GlnPQ has evolved to transport diverse substrates via different paths and to optimally acquire the abundant and essential amino acid glutamine. PMID:26553850

  4. Involvement of the L-Type Amino Acid Transporter Lat2 in the Transport of 3,3'-Diiodothyronine across the Plasma Membrane.

    PubMed

    Kinne, Anita; Wittner, Melanie; Wirth, Eva K; Hinz, Katrin M; Schülein, Ralf; Köhrle, Josef; Krause, Gerd

    2015-09-01

    Thyroid hormones are transported across cell membranes by transmembrane transporter proteins, for example by members of the monocarboxylate transporter (MCT) and the L-type amino acid transporter (LAT) families. LATs consist of a light chain (e.g. LAT2) and a heavy chain (CD98), which is essential for their cell surface expression and functionality. The specificity of Lat2 for thyroid hormones and their metabolites and its role in their transport was not fully clear. This fact motivated us to establish a cell system to elucidate the uptake of thyroid hormones and their metabolites by mouse Lat2. The coinjection of cRNA coding for Lat2 and CD98 into Xenopus laevis oocytes resulted in a markedly increased level of 3,3'-diiodo-L-thyronine (3,3'-T2) and to some extent also enhanced T3 transport. To gain insight into properties of thyroid hormones and their metabolites transported by Lat2, we inhibited 3,3'-T2 uptake by various iodothyronine derivatives. T1 and T2 derivatives as well as 2-aminobicyclo-[2, 2,1]-heptane-2-carboxylic acid strongly competed with 3,3'-T2 uptake. In addition, we performed T2 uptake measurements with the thyroid hormone-specific transporter MCT8. For both Lat2 and MCT8, Km values in a low micromolar range were calculated. We demonstrated that oocytes are a suitable system for thyroid hormone transport studies mediated by Lat2. Our data indicates that Lat2 compared to other thyroid hormone transporters prefers 3,3'-T2 as the substrate. Thus, Lat2 might contribute to the availability of thyroid hormone by importing and/or exporting 3,3'-T2, which is generated either by T3 inactivation or by rapid deiodinase 1-mediated rT3 degradation. PMID:26601072

  5. Road Transportable Analytical Laboratory (RTAL) system

    SciTech Connect

    Finger, S.M.

    1995-10-01

    The goal of the Road Transportable Analytical Laboratory (RTAL) Project is the development and demonstration of a system to meet the unique needs of the DOE for rapid, accurate analysis of a wide variety of hazardous and radioactive contaminants in soil, groundwater, and surface waters. This laboratory system has been designed to provide the field and laboratory analytical equipment necessary to detect and quantify radionuclides, organics, heavy metals and other inorganic compounds. The laboratory system consists of a set of individual laboratory modules deployable independently or as an interconnected group to meet each DOE site`s specific needs.

  6. Human Transportation System (HTS) study, volume 2

    NASA Technical Reports Server (NTRS)

    Lance, N.; Geyer, M. S.; Gaunce, M. T.

    1993-01-01

    This report summarizes work completed under the Human Transportation System Study. This study was conducted by the New Initiatives Office at JSC with the technical support of Boeing, General Dynamics, Lockheed, McDonnell-Douglas, Martin Marietta, and Rockwell. The study was designed to generate information on determining the appropriate path to follow for new system development to meet the Nation's space transportation needs. The study evaluates 18 transportation architecture options using a parametric set of mission requirements. These options include use of current systems (e.g., Shuttle, Titan, etc. ) as well as proposed systems (e.g., PLS, Single-Stage-to-Orbit, etc.) to assess the impact of various considerations, such as the cost of alternate access, or the benefit of separating people and cargo. The architecture options are compared to each other with six measurable evaluation criteria or attributes. They are: funding profile, human safety, probability of mission success, architecture cost risk, launch schedule confidence, and environmental impact. Values for these attributes are presented for the architecture options, with pertinent conclusions and recommendations.

  7. Human Transportation System (HTS) study, volume 2

    NASA Astrophysics Data System (ADS)

    Lance, N.; Geyer, M. S.; Gaunce, M. T.

    1993-10-01

    This report summarizes work completed under the Human Transportation System Study. This study was conducted by the New Initiatives Office at JSC with the technical support of Boeing, General Dynamics, Lockheed, McDonnell-Douglas, Martin Marietta, and Rockwell. The study was designed to generate information on determining the appropriate path to follow for new system development to meet the Nation's space transportation needs. The study evaluates 18 transportation architecture options using a parametric set of mission requirements. These options include use of current systems (e.g., Shuttle, Titan, etc. ) as well as proposed systems (e.g., PLS, Single-Stage-to-Orbit, etc.) to assess the impact of various considerations, such as the cost of alternate access, or the benefit of separating people and cargo. The architecture options are compared to each other with six measurable evaluation criteria or attributes. They are: funding profile, human safety, probability of mission success, architecture cost risk, launch schedule confidence, and environmental impact. Values for these attributes are presented for the architecture options, with pertinent conclusions and recommendations.

  8. Designing Novel Nanoformulations Targeting Glutamate Transporter Excitatory Amino Acid Transporter 2: Implications in Treating Drug Addiction

    PubMed Central

    Rao, PSS; Yallapu, Murali M.; Sari, Youssef; Fisher, Paul B.; Kumar, Santosh

    2015-01-01

    Chronic drug abuse is associated with elevated extracellular glutamate concentration in the brain reward regions. Deficit of glutamate clearance has been identified as a contributing factor that leads to enhanced glutamate concentration following extended drug abuse. Importantly, normalization of glutamate level through induction of glutamate transporter 1 (GLT1)/ excitatory amino acid transporter 2 (EAAT2) expression has been described in several in vivo studies. GLT1 upregulators including ceftriaxone, a beta-lactam antibiotic, have been effective in attenuating drug-seeking and drug-consumption behavior in rodent models. However, potential obstacles toward clinical translation of GLT1 (EAAT2) upregulators as treatment for drug addiction might include poor gastrointestinal absorption, serious peripheral adverse effects, and/or suboptimal CNS concentrations. Given the growing success of nanotechnology in targeting CNS ailments, nanoformulating known GLT1 (EAAT2) upregulators for selective uptake across the blood brain barrier presents an ideal therapeutic approach for treating drug addiction. In this review, we summarize the results obtained with promising GLT1 (EAAT2) inducing compounds in animal models recapitulating drug addiction. Additionally, the various nanoformulations that can be employed for selectively increasing the CNS bioavailability of GLT1 (EAAT2) upregulators are discussed. Finally, the applicability of GLT1 (EAAT2) induction via central delivery of drug-loaded nanoformulations is described. PMID:26635971

  9. Regulatory signals for intestinal amino acid transporters and peptidases

    SciTech Connect

    Ferraris, R.P.; Kwan, W.W.; Diamond, J. )

    1988-08-01

    Dietary protein ultimately regulates many processes involved in protein digestion, but it is often unclear whether proteins themselves, peptides, or amino acids (AAs) are the proximate regulatory signal. Hence the authors compared several processes involved in protein digestion in mice adapted to one of three rations, identical except for containing 54% of either casein, a partial hydrolysate of casein, or a free AA mixture simulating a complete hydrolysate of casein. The authors measured brush-border uptakes of seven AAs that variously serve as substrates for four AA transporters, and brush-border and cytosolic activities of four peptidases. The three rations yielded essentially the same AA uptake rates. Peptidase activities tended to be lower on the AA ration than on the protein ration. In other studies, all three rations yielded the same rates of brush-border peptide uptake; protein is only modestly more effective than AAs at inducing synthesis of pancreatic proteases; and, depending on the animal species, protein is either much less or much more effective than AAs at stimulating release of cholecystokinin and hence of pancreatic enzymes. Thus the regulators of each process involved in protein digestion are not necessarily that process's substrate.

  10. Low energy beam transport system developments

    SciTech Connect

    Dudnikov, V.; Han, B.; Stockli, M.; Welton, R.; Dudnikova, G.

    2015-04-08

    For high brightness beam production it is important to preserve the brightness in the low energy beam transport system (LEBT) used to transport and match the ion beams to the next stage of acceleration, usually an RFQ. While electrostatic focusing can be problematic for high current beam transport, reliable electrostatic LEBT operation has been demonstrated with H{sup −} beams up to 60 mA. Now, however, it is commonly accepted that an optimal LEBT for high current accelerator applications consists of focusing solenoids with space charge compensation. Two-solenoid LEBTs are successfully used for high current (>100 mA) proton beam transport. Preservation of low emittances (~0.15 π mm-mrad) requires the addition of a heavy gas (Xe, Kr), which causes ~5% of proton loss in a 1 m long LEBT. Similar Xe densities would be required to preserve low emittances of H{sup −} beams, but such gas densities cause unacceptably high H{sup −} beam losses. A short LEBT with only one short solenoid, movable for RFQ matching, can be used for reduced negative ion stripping. A strong electrostatic-focusing LEBT has been successfully adopted for transport of high current H{sup −} beams in the SNS Front End. Some modifications of such electrostatic LEBTs are expected to improve the reliable transport of intense positive and negative ion beams without greatly degrading their low emittances. We concentrate on processes that determine the beam brightness degradation and on their prevention. Proposed improvements to the SNS electrostatic LEBT are discussed.

  11. Controlled ecological life support system: Transportation analysis

    NASA Technical Reports Server (NTRS)

    Gustan, E.; Vinopal, T.

    1982-01-01

    This report discusses a study utilizing a systems analysis approach to determine which NASA missions would benefit from controlled ecological life support system (CELSS) technology. The study focuses on manned missions selected from NASA planning forecasts covering the next half century. Comparison of various life support scenarios for the selected missions and characteristics of projected transportation systems provided data for cost evaluations. This approach identified missions that derived benefits from a CELSS, showed the magnitude of the potential cost savings, and indicated which system or combination of systems would apply. This report outlines the analytical approach used in the evaluation, describes the missions and systems considered, and sets forth the benefits derived from CELSS when applicable.

  12. Fatty Acid-Binding Protein 5 Facilitates the Blood-Brain Barrier Transport of Docosahexaenoic Acid.

    PubMed

    Pan, Yijun; Scanlon, Martin J; Owada, Yuji; Yamamoto, Yui; Porter, Christopher J H; Nicolazzo, Joseph A

    2015-12-01

    The brain has a limited ability to synthesize the essential polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) from its omega-3 fatty acid precursors. Therefore, to maintain brain concentrations of this PUFA at physiological levels, plasma-derived DHA must be transported across the blood-brain barrier (BBB). While DHA is able to partition into the luminal membrane of brain endothelial cells, its low aqueous solubility likely limits its cytosolic transfer to the abluminal membrane, necessitating the requirement of an intracellular carrier protein to facilitate trafficking of this PUFA across the BBB. As the intracellular carrier protein fatty acid-binding protein 5 (FABP5) is expressed at the human BBB, the current study assessed the putative role of FABP5 in the brain endothelial cell uptake and BBB transport of DHA in vitro and in vivo, respectively. hFAPB5 was recombinantly expressed and purified from Escherichia coli C41(DE3) cells and the binding affinity of DHA to hFABP5 assessed using isothermal titration calorimetry. The impact of FABP5 siRNA on uptake of (14)C-DHA into immortalized human brain microvascular endothelial (hCMEC/D3) cells was assessed. An in situ transcardiac perfusion method was optimized in C57BL/6 mice and subsequently used to compare the BBB influx rate (Kin) of (14)C-DHA between FABP5-deficient (FABP5(-/-)) and wild-type (FABP5(+/+)) C57BL/6 mice. DHA bound to hFABP5 with an equilibrium dissociation constant of 155 ± 8 nM (mean ± SEM). FABP5 siRNA transfection decreased hCMEC/D3 mRNA and protein expression of FABP5 by 53.2 ± 5.5% and 44.8 ± 13.7%, respectively, which was associated with a 14.1 ± 2.7% reduction in (14)C-DHA cellular uptake. By using optimized conditions for the in situ transcardiac perfusion (a 1 min preperfusion (10 mL/min) followed by perfusion of (14)C-DHA (1 min)), the Kin of (14)C-DHA was 0.04 ± 0.01 mL/g/s. Relative to FABP5(+/+) mice, the Kin of (14)C-DHA decreased 36.7 ± 12.4% in FABP5(-/-) mice

  13. Plasmodesmata localizing proteins regulate transport and signaling during systemic acquired immunity in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Systemic acquired resistance (SAR) in plants is mediated by the signaling molecules azelaic acid (AzA),glycerol-3-phosphate (G3P), and salicylic acid (SA).Here, we show that AzA and G3P transport occurs via the symplastic route, which is regulated by channels known as plasmodesmata (PD). In contrast...

  14. Hypertonic stress regulates amino acid transport and cell cycle proteins in chick embryo hepatocytes.

    PubMed

    Bruscalupi, Giovannella; Massimi, Mara; Spagnuolo, Silvana; Fiore, Anna Maria; Leoni, Silvia

    2012-02-01

    Hyperosmotic stress affects cell growth, decreasing cell volume and increasing the uptake of organic osmolytes. However, the sensitivity of embryonic cells to osmotic treatment remains to be established. We have analysed some aspects of cell-cycle control and amino-acid transport in hypertonic conditions during prenatal life. The effects of hyperosmotic stress on amino-acid uptake mediated by system A, (3)H-thymidine incorporation, and regulation of cell-cycle proteins were analysed in chick embryo hepatocytes. Hypertonic stress increased system A activity and caused cell-cycle delay. Effects on amino-acid transport involved p38 kinase activation and new carrier synthesis. Cyclin D1, cdk4 (cyclin-dependent kinase 4) and PCNA (proliferating-cell nuclear antigen) levels decreased, whereas cyclin E, p21 and p53 levels were unchanged. Incorporation of (3)H-leucine indicated decreased synthesis of cyclin D1. In contrast, analysis of mRNA by qRT-PCR (quantitative real-time PCR) showed a net increase of cyclin D1 transcripts, suggesting post-transcriptional regulation. The data show that chick embryo hepatocytes respond to hyperosmotic conditions by arresting cell growth to prevent DNA damage and increasing osmolyte uptake to regulate cell volume, indicating that the adaptive response to environmental stress exists during prenatal life.

  15. Transport mechanism and regulatory properties of the human amino acid transporter ASCT2 (SLC1A5).

    PubMed

    Scalise, Mariafrancesca; Pochini, Lorena; Panni, Simona; Pingitore, Piero; Hedfalk, Kristina; Indiveri, Cesare

    2014-11-01

    The kinetic mechanism of the transport catalyzed by the human glutamine/neutral amino acid transporter hASCT2 over-expressed in P. pastoris was determined in proteoliposomes by pseudo-bi-substrate kinetic analysis of the Na(+)-glutamineex/glutaminein transport reaction. A random simultaneous mechanism resulted from the experimental analysis. Purified functional hASCT2 was chemically cross-linked to a stable dimeric form. The oligomeric structure correlated well with the kinetic mechanism of transport. Half-saturation constants (Km) of the transporter for the other substrates Ala, Ser, Asn and Thr were measured both on the external and internal side. External Km were much lower than the internal ones confirming the asymmetry of the transporter. The electric nature of the transport reaction was determined imposing a negative inside membrane potential generated by K(+) gradients in the presence of valinomycin. The transport reaction resulted to be electrogenic and the electrogenicity originated from external Na(+). Internal Na(+) exerted a stimulatory effect on the transport activity which could be explained by a regulatory, not a counter-transport, effect. Native and deglycosylated hASCT2 extracted from HeLa showed the same transport features demonstrating that the glycosyl moiety has no role in transport function. Both in vitro and in vivo interactions of hASCT2 with the scaffold protein PDZK1 were revealed.

  16. Heat transport system, method and material

    DOEpatents

    Musinski, D.L.

    1987-04-28

    A heat transport system, method and composite material are disclosed in which a plurality of hollow spherical shells or microspheres having an outside diameter of less than or equal to 500 microns are encapsulated or embedded within a bulk material. Each shell has captured therein a volatile working fluid, such that each shell operates as a microsized heat pipe for conducting heat through the composite structure. 1 fig.

  17. Cargo transportation by airships: A systems study

    NASA Technical Reports Server (NTRS)

    Huang, C. J.; Dalton, C.

    1976-01-01

    A systems engineering study of a lighter than air airship transportation system was conducted. The feasibility of the use of airships in hauling cargo was demonstrated. Social, legal, environmental and political factors were considered as well as the technical factors necessary to design an effective airship transportation system. In order to accomplish an effective airship transportation program two phases of implementation were recommended. Phase I would involve a fleet of rigid airships of 3.5 million cubic feet displacement capable of carrying 25 tons of cargo internal to the helium-filled gas bag. The Phase I fleet would demonstrate the economic and technical feasibility of modern-day airships while providing a training capability for the construction and operation of larger airships. The Phase II portion would be a fleet of rigid airships of 12 million cubic feet displacement capable of carrying a cargo of 100 tons a distance of 2,000 miles at a cruising speed of 60 mph. An economic analysis is given for a variety of missions for both Phase I and Phase II airships.

  18. The Palm Desert renewable [hydrogen] transportation system

    SciTech Connect

    Chamberlin, C.E.; Lehman, P.

    1998-08-01

    This paper describes the Schatz Energy Research Center (SERC) progress on the Palm Desert Renewable Hydrogen Transportation System Project for the period June 1997 through May 1998. The project began in March 1996. The goal of the Palm Desert Project is to develop a clean and sustainable transportation system for a community. The project demonstrates the practical utility of hydrogen as a transportation fuel and the proton exchange membrane (PEM) fuel cell as a vehicle power system. The project includes designing and building 4 fuel cell powered vehicles, a solar hydrogen generating and refueling station, and a fuel cell vehicle diagnostic center. Over this last year, SERC has built a fuel cell powered neighborhood electric vehicle and delivered it to the City of Palm Desert. The design of the hydrogen refueling station is near completion and it is anticipated that construction will be complete in the fall of 1998. The vehicles are currently being refueled at a temporary refueling station. The diagnostic center is being designed and maintenance procedures as well as computer diagnostic programs for the fuel cell vehicles are being developed. City employees are driving the vehicles daily and monitoring data are being collected. The drivers are pleased with the performance of the vehicles.

  19. The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids.

    PubMed

    Gasnier, Bruno

    2004-02-01

    The SLC32 family comprises a single member: the vesicular inhibitory amino acid transporter (VIAAT) or vesicular GABA transporter (VGAT). It belongs to a eukaryotic-specific superfamily of H(+)-coupled amino acid transporters, which also comprises the mammalian SLC36 and SLC38 transporters. VIAAT exchanges GABA or glycine for protons. It is present on synaptic vesicles of GABAergic and glycinergic neurons, and in some endocrine cells, where it ensures the H(+)-ATPase-driven uptake, and subsequent exocytotic release, of inhibitory amino acids. Despite a similar function in vesicular neurotransmitter loading, VIAAT is not related to the vesicular glutamate transporter (VGLUT, SLC17) or the vesicular monoamine transporter/vesicular acetylcholine transporter (VMAT/VACHT, SLC18) proteins.

  20. Inducible expression and pharmacology of the human excitatory amino acid transporter 2 subtype of L-glutamate transporter.

    PubMed

    Dunlop, J; Lou, Z; Zhang, Y; McIlvain, H B

    1999-12-01

    1. In this study we have examined the use of the ecdysone-inducible mammalian expression system (Invitrogen) for the regulation of expression of the predominant L-glutamate transporter EAAT2 (Excitatory Amino Acid Transporter) in HEK 293 cells. 2. HEK 293 cells which were stably transformed with the regulatory vector pVgRXR (EcR 293 cells) were used for transfection of the human EAAT2 cDNA using the inducible vector pIND and a clone designated HEK/EAAT2 was selected for further characterization. 3. Na+-dependent L-glutamate uptake activity (3.2 pmol min-1 mg-1) was observed in EcR 293 cells and this was increased approximately 2 fold in the uninduced HEK/EAAT2 cells, indicating a low level of basal EAAT2 activity in the absence of exogenous inducing agent. Exposure of HEK/EAAT2 cells to the ecdysone analogue Ponasterone A (10 microM for 24 h) resulted in a > or = 10 fold increase in the Na+-dependent activity. 4. L-glutamate uptake into induced HEK/EAAT2 cells followed first-order Michaelis-Menten kinetics and Eadie-Hofstee transformation of the saturable uptake data produced estimates of kinetic parameters as follows; Km 52.7+/-7.5 microM, Vmax 3.8+/-0.9 nmol min-1 mg-1 protein. 5. The pharmacological profile of the EAAT2 subtype was characterized using a series of L-glutamate transport inhibitors and the rank order of inhibitory potency was similar to that described previously for the rat homologue GLT-1 and in synaptosomal preparations from rat cortex. 6. Addition of the EAAT2 modulator arachidonic acid resulted in an enhancement (155+/-5% control in the presence of 30 microM) of the L-glutamate transport capacity in the induced HEK/EAAT2 cells. 7. This study demonstrates that the expression of EAAT2 can be regulated in a mammalian cell line using the ecdysone-inducible mammalian expression system.

  1. Visualizing Mobility of Public Transportation System.

    PubMed

    Zeng, Wei; Fu, Chi-Wing; Arisona, Stefan Müller; Erath, Alexander; Qu, Huamin

    2014-12-01

    Public transportation systems (PTSs) play an important role in modern cities, providing shared/massive transportation services that are essential for the general public. However, due to their increasing complexity, designing effective methods to visualize and explore PTS is highly challenging. Most existing techniques employ network visualization methods and focus on showing the network topology across stops while ignoring various mobility-related factors such as riding time, transfer time, waiting time, and round-the-clock patterns. This work aims to visualize and explore passenger mobility in a PTS with a family of analytical tasks based on inputs from transportation researchers. After exploring different design alternatives, we come up with an integrated solution with three visualization modules: isochrone map view for geographical information, isotime flow map view for effective temporal information comparison and manipulation, and OD-pair journey view for detailed visual analysis of mobility factors along routes between specific origin-destination pairs. The isotime flow map linearizes a flow map into a parallel isoline representation, maximizing the visualization of mobility information along the horizontal time axis while presenting clear and smooth pathways from origin to destinations. Moreover, we devise several interactive visual query methods for users to easily explore the dynamics of PTS mobility over space and time. Lastly, we also construct a PTS mobility model from millions of real passenger trajectories, and evaluate our visualization techniques with assorted case studies with the transportation researchers.

  2. Transport and catabolism of the sialic acids N-glycolylneuraminic acid and 3-keto-3-deoxy-D-glycero-D-galactonononic acid by Escherichia coli K-12.

    PubMed

    Hopkins, Adam P; Hawkhead, Judith A; Thomas, Gavin H

    2013-10-01

    Escherichia coli can transport and catabolize the common sialic acid, N-acetylneuraminic acid (Neu5Ac), as a sole source of carbon and nitrogen, which is an important mucus-derived carbon source in the mammalian gut. Herein we demonstrate that E. coli can also grow efficiently on the related sialic acids, N-glycolylneuraminic acid (Neu5Gc) and 3-keto-3-deoxy-D-glycero-D-galactonononic acid (KDN), which are transported via the sialic acid transporter NanT and catabolized using the sialic acid aldolase NanA. Catabolism of Neu5Gc uses the same pathway as Neu5Ac, likely producing glycolate instead and acetate during its breakdown and catabolism of KDN requires NanA activity, while other components of the Neu5Ac catabolism pathway are non-essential. We also demonstrate that these two sialic acids can support growth of an E. coli ∆nanT strain expressing sialic acid transporters from two bacterial pathogens, namely the tripartite ATP-independent periplasmic transporter SiaPQM from Haemophilus influenzae and the sodium solute symport transporter STM1128 from Salmonella enterica ssp. Typhimurium, suggesting that the ability to use Neu5Gc and KDN in addition to Neu5Ac is present in a number of human pathogens.

  3. Acid-extrusion from tissue: the interplay between membrane transporters and pH buffers.

    PubMed

    Hulikova, Alzbeta; Harris, Adrian L; Vaughan-Jones, Richard D; Swietach, Pawel

    2012-01-01

    The acid-base balance of cells is related to the concentration of free H⁺ ions. These are highly reactive, and their intracellular concentration must be regulated to avoid detrimental effects to the cell. H⁺ ion dynamics are influenced by binding to chelator substances ('buffering'), and by the production, diffusion and membrane-transport of free H⁺ ions or of the H⁺-bound chelators. Intracellular pH (pHi) regulation aims to balance this system of diffusion-reaction-transport processes at a favourable steady-state pHi. The ability of cells to regulate pHi may set a limit to tissue growth and can be subject to selection pressures. Cancer cells have been postulated to respond favourably to such selection pressures by evolving a better means of pHi regulation. A particularly important feature of tumour pHi regulation is acid-extrusion, which involves H⁺-extrusion and HCO₃⁻-uptake by membrane-bound transporter-proteins. Extracellular CO₂/HCO₃⁻ buffer facilitates these membrane-transport processes. As a mobile pH-buffer, CO₂/HCO₃⁻ protects the extracellular space from excessive acidification that could otherwise inhibit further acid-extrusion. CO₂/HCO₃⁻ also provides substrate for HCO₃⁻-transporters. However, the inherently slow reaction kinetics of CO₂/HCO₃⁻ can be rate-limiting for acid-extrusion. To circumvent this, cells can express extracellular-facing carbonic anhydrase enzymes to accelerate the attainment of equilibrium between CO₂, HCO₃⁻ and H⁺. The acid-extrusion apparatus has been proposed as a target for anti-cancer therapy. The major targets include H⁺ pumps, Na⁺/H⁺ exchangers and carbonic anhydrases. The effectiveness of such therapy will depend on the correct identification of rate-limiting steps in pHi regulation in a specific type of cancer. PMID:22360560

  4. Next generation: In-space transportation system(s)

    NASA Technical Reports Server (NTRS)

    Huffaker, Fredrick; Redus, Jerry; Kelley, David L.

    1991-01-01

    The development of the next generation In-Space Transportation System presents a unique challenge to the design of a propulsion system for the Space Exploration Initiative (SEI). Never before have the requirements for long-life, multiple mission use, space basing, high reliability, man-rating, and minimum maintenance come together with performance in one system that must protect the lives of space travelers, support the mission logistics needs, and do so at an acceptable cost. The challenge that is presented is to quantify the bounds of these requirements. The issue is one of degree. The length of acceptable life in space, the time it takes for reuse to pay off, and the degree to which space basing is practical (full, partial, or expended) are the issues that determine the reusable bounds of a design and include dependability, contingency capabilities, resilency, and minimum dependence on a maintenance node in preparation for and during a mission. Missions to planet earth, other non-NASA missions, and planetary missions will provide important but less demanding requirements for the transportation systems of the future. The mission proposed for the SEI require a family of transportation vehicles to meet the requirements for establishing a permanent human presence on the Moon and eventually on Mars. Specialized vehicles are needed to accomplish the different phases of each mission. These large scale missions require assembly in space and will provide the greatest usage of the planned integrated transportation system. The current approach to defining the In-Space Transportation System for the SEI Moon missions with later Mars mission applications is presented. Several system development options, propulsion concepts, current/proposed activities are reviewed, and key propulsion design criteria, issues, and technology challenges for the next generation In-Space Transportation System(s) are outlined.

  5. High Energy Particle Transport Code System.

    2003-12-17

    Version 00 NMTC/JAM is an upgraded version of the code CCC-694/NMTC-JAERI97, which was developed in 1982 at JAERI and is based on the CCC-161/NMTC code system. NMTC/JAM simulates high energy nuclear reactions and nuclear meson transport processes. The applicable energy range of NMTC/JAM was extended in principle up to 200 GeV for nucleons and mesons by introducing the high energy nuclear reaction code Jet-Aa Microscopic (JAM) for the intra-nuclear cascade part. For the evaporation andmore » fission process, a new model, GEM, can be used to describe the light nucleus production from the excited residual nucleus. According to the extension of the applicable energy, the nucleon-nucleus non-elastic, elastic and differential elastic cross section data were upgraded. In addition, the particle transport in a magnetic field was implemented for beam transport calculations. Some new tally functions were added, and the format of input and output of data is more user friendly. These new calculation functions and utilities provide a tool to carry out reliable neutronics study of a large scale target system with complex geometry more accurately and easily than with the previous model. It implements an intranuclear cascade model taking account of the in-medium nuclear effects and the preequilibrium calculation model based on the exciton one. For treating the nucleon transport process, the nucleon-nucleus cross sections are revised to those derived by the systematics of Pearlstein. Moreover, the level density parameter derived by Ignatyuk is included as a new option for particle evaporation calculation. A geometry package based on the Combinatorial Geometry with multi-array system and the importance sampling technique is implemented in the code. Tally function is also employed for obtaining such physical quantities as neutron energy spectra, heat deposition and nuclide yield without editing a history file. The code can simulate both the primary spallation reaction and the

  6. Miniature Heat Transport System for Nanosatellite Technology

    NASA Technical Reports Server (NTRS)

    Douglas, Donya M,

    1999-01-01

    The scientific understanding of key physical processes between the Sun and the Earth require simultaneous measurements from many vantage points in space. Nano-satellite technologies will enable a class of constellation missions for the NASA Space Science Sun-Earth Connections. This recent emphasis on the implementation of smaller satellites leads to a requirement for development of smaller subsystems in several areas. Key technologies under development include: advanced miniaturized chemical propulsion; miniaturized sensors; highly integrated, compact electronics; autonomous onboard and ground operations; miniatures low power tracking techniques for orbit determination; onboard RF communications capable of transmitting data to the ground from far distances; lightweight efficient solar array panels; lightweight, high output battery cells; lightweight yet strong composite materials for the nano-spacecraft and deployer-ship structures. These newer smaller systems may have higher power densities and higher thermal transport requirements than seen on previous small satellites. Furthermore, the small satellites may also have a requirement to maintain thermal control through extended earth shadows, possibly up to 8 hours long. Older thermal control technology, such as heaters, thermostats, and heat pipes, may not be sufficient to meet the requirements of these new systems. Conversely, a miniature two-phase heat transport system (Mini-HTS) such as a Capillary Pumped Loop (CPL) or Loop Heat Pipe (LBP) is a viable alternative. A Mini-HTS can provide fine temperature control, thermal diode action, and a highly efficient means of heat transfer. The Mini-HTS would have power capabilities in the range of tens of watts or less and provide thermal control over typical spacecraft ranges. The Mini-HTS would allow the internal portion of the spacecraft to be thermally isolated from the external radiator, thus protecting the internal components from extreme cold temperatures during an

  7. Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle.

    PubMed Central

    Biolo, G; Declan Fleming, R Y; Wolfe, R R

    1995-01-01

    We have investigated the mechanisms of the anabolic effect of insulin on muscle protein metabolism in healthy volunteers, using stable isotopic tracers of amino acids. Calculations of muscle protein synthesis, breakdown, and amino acid transport were based on data obtained with the leg arteriovenous catheterization and muscle biopsy. Insulin was infused (0.15 mU/min per 100 ml leg) into the femoral artery to increase femoral venous insulin concentration (from 10 +/- 2 to 77 +/- 9 microU/ml) with minimal systemic perturbations. Tissue concentrations of free essential amino acids decreased (P < 0.05) after insulin. The fractional synthesis rate of muscle protein (precursor-product approach) increased (P < 0.01) after insulin from 0.0401 +/- 0.0072 to 0.0677 +/- 0.0101%/h. Consistent with this observation, rates of utilization for protein synthesis of intracellular phenylalanine and lysine (arteriovenous balance approach) also increased from 40 +/- 8 to 59 +/- 8 (P < 0.05) and from 219 +/- 21 to 298 +/- 37 (P < 0.08) nmol/min per 100 ml leg, respectively. Release from protein breakdown of phenylalanine, leucine, and lysine was not significantly modified by insulin. Local hyperinsulinemia increased (P < 0.05) the rates of inward transport of leucine, lysine, and alanine, from 164 +/- 22 to 200 +/- 25, from 126 +/- 11 to 221 +/- 30, and from 403 +/- 64 to 595 +/- 106 nmol/min per 100 ml leg, respectively. Transport of phenylalanine did not change significantly. We conclude that insulin promoted muscle anabolism, primarily by stimulating protein synthesis independently of any effect on transmembrane transport. Images PMID:7860765

  8. Abundance of amino acid transporters involved in mTORC1 activation in skeletal muscle of neonatal pigs is developmentally regulated

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously we demonstrated that the insulinand amino acid-induced activation of the mammalian target of rapamycin complex 1 (mTORC1) is developmentally regulated in neonatal pigs. Recent studies have indicated that members of the System A transporter (SNAT2), the System N transporter (SNAT3), the Sy...

  9. PtAAP11, a high affinity amino acid transporter specifically expressed in differentiating xylem cells of poplar.

    PubMed

    Couturier, Jérémy; de Faÿ, Elisabeth; Fitz, Michael; Wipf, Daniel; Blaudez, Damien; Chalot, Michel

    2010-06-01

    Amino acids are the currency of nitrogen exchange between source and sink tissues in plants and constitute a major source of the components used for cellular growth and differentiation. The characterization of a new amino acid transporter belonging to the amino acid permease (AAP) family, AAP11, expressed in the perennial species Populus trichocarpa is reported here. PtAAP11 expression analysis was performed by semi-quantitative RT-PCR and GUS activity after poplar transformation. PtAAP11 function was studied in detail by heterologous expression in yeast. The poplar genome contains 14 putative AAPs which is quite similar to other species analysed except Arabidopsis. PtAAP11 was mostly expressed in differentiating xylem cells in different organs. Functional characterization demonstrated that PtAAP11 was a high affinity amino acid transporter, more particularly for proline. Compared with other plant amino acid transporters, PtAAP11 represents a novel high-affinity system for proline. Thus, the functional characterization and expression studies suggest that PtAAP11 may play a major role in xylogenesis by providing proline required for xylem cell wall proteins. The present study provides important information highlighting the role of a specific amino acid transporter in xylogenesis in poplar.

  10. Heavy particle transport in sputtering systems

    NASA Astrophysics Data System (ADS)

    Trieschmann, Jan

    2015-09-01

    This contribution aims to discuss the theoretical background of heavy particle transport in plasma sputtering systems such as direct current magnetron sputtering (dcMS), high power impulse magnetron sputtering (HiPIMS), or multi frequency capacitively coupled plasmas (MFCCP). Due to inherently low process pressures below one Pa only kinetic simulation models are suitable. In this work a model appropriate for the description of the transport of film forming particles sputtered of a target material has been devised within the frame of the OpenFOAM software (specifically dsmcFoam). The three dimensional model comprises of ejection of sputtered particles into the reactor chamber, their collisional transport through the volume, as well as deposition of the latter onto the surrounding surfaces (i.e. substrates, walls). An angular dependent Thompson energy distribution fitted to results from Monte-Carlo simulations is assumed initially. Binary collisions are treated via the M1 collision model, a modified variable hard sphere (VHS) model. The dynamics of sputtered and background gas species can be resolved self-consistently following the direct simulation Monte-Carlo (DSMC) approach or, whenever possible, simplified based on the test particle method (TPM) with the assumption of a constant, non-stationary background at a given temperature. At the example of an MFCCP research reactor the transport of sputtered aluminum is specifically discussed. For the peculiar configuration and under typical process conditions with argon as process gas the transport of aluminum sputtered of a circular target is shown to be governed by a one dimensional interaction of the imposed and backscattered particle fluxes. The results are analyzed and discussed on the basis of the obtained velocity distribution functions (VDF). This work is supported by the German Research Foundation (DFG) in the frame of the Collaborative Research Centre TRR 87.

  11. Hyperspectral range imaging for transportation systems evaluation

    NASA Astrophysics Data System (ADS)

    Bridgelall, Raj; Rafert, J. B.; Atwood, Don; Tolliver, Denver D.

    2016-04-01

    Transportation agencies expend significant resources to inspect critical infrastructure such as roadways, railways, and pipelines. Regular inspections identify important defects and generate data to forecast maintenance needs. However, cost and practical limitations prevent the scaling of current inspection methods beyond relatively small portions of the network. Consequently, existing approaches fail to discover many high-risk defect formations. Remote sensing techniques offer the potential for more rapid and extensive non-destructive evaluations of the multimodal transportation infrastructure. However, optical occlusions and limitations in the spatial resolution of typical airborne and space-borne platforms limit their applicability. This research proposes hyperspectral image classification to isolate transportation infrastructure targets for high-resolution photogrammetric analysis. A plenoptic swarm of unmanned aircraft systems will capture images with centimeter-scale spatial resolution, large swaths, and polarization diversity. The light field solution will incorporate structure-from-motion techniques to reconstruct three-dimensional details of the isolated targets from sequences of two-dimensional images. A comparative analysis of existing low-power wireless communications standards suggests an application dependent tradeoff in selecting the best-suited link to coordinate swarming operations. This study further produced a taxonomy of specific roadway and railway defects, distress symptoms, and other anomalies that the proposed plenoptic swarm sensing system would identify and characterize to estimate risk levels.

  12. An overview of European space transportation systems

    NASA Technical Reports Server (NTRS)

    Lo, R. E.

    1985-01-01

    With the completion of the launch rocket series Ariane 1 to 4, Europe will have reached the same capacity to transport commercial payloads as the USA has with the Space Shuttle and the kick stages which are presently operative. The near term development of these capacities would require Europe to develop a larger launch rocket, Araine 5. Further motivations for this rocket are access to manned spaceflight, the development of an European space station, and the demand for shuttle technology. Shuttle technology is the subject of research being done in France on the winged re-entry vehicle Hermes. Operation of the European space station Columbus will require development of an interorbital transport system to facilitate traffic between the various segments of the space station. All European space transportation systems will have to match their quality to that of the other countries involve in space flight. All areas of development are marked not only by possible cooperation but also by increased competition because of increasing commercialization of space flight.

  13. National Space Transportation System (NSTS) technology needs

    NASA Technical Reports Server (NTRS)

    Winterhalter, David L.; Ulrich, Kimberly K.

    1990-01-01

    The National Space Transportation System (NSTS) is one of the Nation's most valuable resources, providing manned transportation to and from space in support of payloads and scientific research. The NSTS program is currently faced with the problem of hardware obsolescence, which could result in unacceptable schedule and cost impacts to the flight program. Obsolescence problems occur because certain components are no longer being manufactured or repair turnaround time is excessive. In order to achieve a long-term, reliable transportation system that can support manned access to space through 2010 and beyond, NASA must develop a strategic plan for a phased implementation of enhancements which will satisfy this long-term goal. The NSTS program has initiated the Assured Shuttle Availability (ASA) project with the following objectives: eliminate hardware obsolescence in critical areas, increase reliability and safety of the vehicle, decrease operational costs and turnaround time, and improve operational capability. The strategy for ASA will be to first meet the mandatory needs - keep the Shuttle flying. Non-mandatory changes that will improve operational capability and enhance performance will then be considered if funding is adequate. Upgrade packages should be developed to install within designated inspection periods, grouped in a systematic approach to reduce cost and schedule impacts, and allow the capability to provide a Block 2 Shuttle (Phase 3).

  14. Transporters in Arabidopsis roots mediating uptake of amino acids at naturally occurring concentrations.

    PubMed

    Svennerstam, Henrik; Jämtgård, Sandra; Ahmad, Iftikhar; Huss-Danell, Kerstin; Näsholm, Torgny; Ganeteg, Ulrika

    2011-07-01

    Recent studies of Arabidopsis have identified several transporters as being important for amino acid uptake. We used Arabidopsis plants with altered expression of lysine histidine transporter 1 (LHT1), amino acid permease 1 (AAP1) and amino acid permease 5 (AAP5) with the aim of disentangling the roles of each transporter in the uptake of different amino acids at naturally occurring concentrations (2-50 μM). LHT1 mutants displayed reduced uptake rates of L-Gln, L-Ala, L-Glu and L-Asp but not of L-Arg or L-Lys, while AAP5 mutants were affected in the uptake of L-Arg and L-Lys only. Double mutants (lht1aap5) exhibited reduced uptake of all tested amino acids. In the concentration range tested, AAP1 mutants did not display altered uptake rates for any of the studied amino acids. Expression analysis of amino acid transporter genes with important root functions revealed no major differences in the individual mutants other than for genes targeted for mutation. We conclude that LHT1 and AAP5, but not AAP1, are crucial for amino acid uptake at concentrations typically found in soils. LHT1 and AAP5 displayed complementary affinity spectra, and no redundancy with respect to gene expression was found between the two transporters, suggesting these two transporters have separate roles in amino acid uptake.

  15. Inhibition of Na+-Taurocholate Co-transporting Polypeptide-mediated Bile Acid Transport by Cholestatic Sulfated Progesterone Metabolites*

    PubMed Central

    Abu-Hayyeh, Shadi; Martinez-Becerra, Pablo; Sheikh Abdul Kadir, Siti H.; Selden, Clare; Romero, Marta R.; Rees, Myrddin; Marschall, Hanns-Ulrich; Marin, Jose J. G.; Williamson, Catherine

    2010-01-01

    Sulfated progesterone metabolite (P4-S) levels are raised in normal pregnancy and elevated further in intrahepatic cholestasis of pregnancy (ICP), a bile acid-liver disorder of pregnancy. ICP can be complicated by preterm labor and intrauterine death. The impact of P4-S on bile acid uptake was studied using two experimental models of hepatic uptake of bile acids, namely cultured primary human hepatocytes (PHH) and Na+-taurocholate co-transporting polypeptide (NTCP)-expressing Xenopus laevis oocytes. Two P4-S compounds, allopregnanolone-sulfate (PM4-S) and epiallopregnanolone-sulfate (PM5-S), reduced [3H]taurocholate (TC) uptake in a dose-dependent manner in PHH, with both Na+-dependent and -independent bile acid uptake systems significantly inhibited. PM5-S-mediated inhibition of TC uptake could be reversed by increasing the TC concentration against a fixed PM5-S dose indicating competitive inhibition. Experiments using NTCP-expressing Xenopus oocytes confirmed that PM4-S/PM5-S are capable of competitively inhibiting NTCP-mediated uptake of [3H]TC. Total serum PM4-S + PM5-S levels were measured in non-pregnant and third trimester pregnant women using liquid chromatography-electrospray tandem mass spectrometry and were increased in pregnant women, at levels capable of inhibiting TC uptake. In conclusion, pregnancy levels of P4-S can inhibit Na+-dependent and -independent influx of taurocholate in PHH and cause competitive inhibition of NTCP-mediated uptake of taurocholate in Xenopus oocytes. PMID:20177056

  16. Technological Support for Logistics Transportation Systems

    NASA Astrophysics Data System (ADS)

    Bujak, Andrzej; Śliwa, Zdzisław; Gębczyńska, Alicja

    The modern world is changing introducing robots, remotely controlled vehicles and other crewless means of transportation to reduce people's mistakes, as the main cause of incidents and crashes during traffic. New technologies are supporting operators and drivers, and according to some studies they can even replace them. Such programs as: AHS, UAH, IVBSS or MTVR are under development to improve traffic flow and its safety, to reduce traffic hazards and crashes. It is necessary to analyze such concepts and implement them boldly, including Polish logistics' companies, new programs, highways' system etc., as they will be applied in the future, so it is necessary to prepare logistics infrastructure ahead of time in order to capitalize on these improvements. The problem is quite urgent as transportation in the country must not be outdated to meet clients' expectations and to keep pace with competing foreign companies.

  17. Mitochondrial transporters involved in oleic acid utilization and glutamate metabolism in yeast.

    PubMed

    Trotter, Pamela J; Adamson, Amy L; Ghrist, Angela C; Rowe, Lindsay; Scott, Lori R; Sherman, Matthew P; Stites, Nicole C; Sun, Yue; Tawiah-Boateng, Mary Anne; Tibbetts, Anne S; Wadington, Megan C; West, Aaron C

    2005-10-01

    Utilization of fatty acids such as oleic acid as sole carbon source by the yeast Saccharomyces cerevisiae requires coordinated function of peroxisomes, where the fatty acids are degraded, and the mitochondria, where oxidation is completed. We identified two mitochondrial oxodicarboxylate transporters, Odc1p and Odc2p, as important in efficient utilization of oleic acid in yeast [Tibbetts et al., Arch. Biochem. Biophys. 406 (2002) 96-104]. Yet, the growth phenotype of odc1delta odc2delta strains indicated that additional transporter(s) were also involved. Here, we identify two putative transporter genes, YMC1 and YMC2, as able to suppress the odc1delta odc2delta growth phenotype. The mRNA levels for both are elevated in the presence of glycerol or oleic acid, as compared to glucose. Ymc1p and Ymc2p are localized to the mitochondria in oleic acid-grown cells. Deletion of all four transporters (quad mutant) prevents growth on oleic acid as sole carbon source, while growth on acetate is retained. It is known that the glutamate-sensitive retrograde signaling pathway is important for upregulation of peroxisomal function in response to oleic acid and the oxodicarboxylate alpha-ketoglutarate is transported out of the mitochondria for synthesis of glutamate. So, citric acid cycle function and glutamate synthesis were examined in transporter mutants. The quad mutant has significantly decreased citrate synthase activity and whole cell alpha-ketoglutarate levels, while isocitrate dehydrogenase activity is unaffected and glutamate dehydrogenase activity is increased 10-fold. Strains carrying only two or three transporter deletions exhibit intermediate affects. 13C NMR metabolic enrichment experiments confirm a defect in glutamate biosynthesis in the quad mutant and, in double and triple mutants, suggest increased cycling of the glutamate backbone in the mitochondria before export. Taken together these studies indicate that these four transporters have overlapping activity, and

  18. Functional expression of two system A glutamine transporter isoforms in rat auditory brainstem neurons

    PubMed Central

    Blot, A.; Billups, D.; Bjørkmo, M.; Quazi, A.Z.; Uwechue, N.M.; Chaudhry, F.A.; Billups, B.

    2009-01-01

    Glutamine plays multiple roles in the CNS, including metabolic functions and production of the neurotransmitters glutamate and GABA. It has been proposed to be taken up into neurons via a variety of membrane transport systems, including system A, which is a sodium-dependent electrogenic amino acid transporter system. In this study, we investigate glutamine transport by application of amino acids to individual principal neurons of the medial nucleus of the trapezoid body (MNTB) in acutely isolated rat brain slices. A glutamine transport current was studied in patch-clamped neurons, which had the electrical and pharmacological properties of system A: it was sodium-dependent, had a non-reversing current-voltage relationship, was activated by proline, occluded by N-(methylamino)isobutyric acid (MeAIB), and was unaffected by 2-aminobicyclo-[2.2.1]-heptane-2-carboxylic acid (BCH). Additionally, we examined the expression of different system A transporter isoforms using immunocytochemical staining with antibodies raised against system A transporter 1 and 2 (SAT1 and SAT2). Our results indicate that both isoforms are expressed in MNTB principal neurons, and demonstrate that functional system A transporters are present in the plasma membrane of neurons. Since system A transport is highly regulated by a number of cellular signaling mechanisms and glutamine then goes on to activate other pathways, the study of these transporters in situ gives an indication of the mechanisms of neuronal glutamine supply as well as points of regulation of neurotransmitter production, cellular signaling and metabolism in the native neuronal environment. PMID:19751803

  19. Transporter-targeted cholic acid-cytarabine conjugates for improved oral absorption.

    PubMed

    Zhang, Dong; Li, Dongpo; Shang, Lei; He, Zhonggui; Sun, Jin

    2016-09-10

    Cytarabine has a poor oral absorption due to its rapid deamination and poor membrane permeability. Bile acid transporters are highly expressed both in enterocytes and hepatocytes and to increase the oral bioavailability and investigate the potential application of cytarabine for liver cancers, a transporter- recognizing prodrug strategy was applied to design and synthesize four conjugates of cytarabine with cholic acid (CA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA) and ursodeoxycholic acid (UDCA). The anticancer activities against HepG2 cells were evaluated by MTT assay and the role of bile acid transporters during cellular transport was investigated in a competitive inhibition experiment. The in vitro and in vivo metabolic stabilities of these conjugates were studied in rat plasma and liver homogenates. Finally, an oral bioavailability study was conducted in rats. All the cholic acid-cytarabine conjugates (40μM) showed potent antiproliferative activities (up to 70%) against HepG2 cells after incubation for 48h. The addition of bile acids could markedly reduce the antitumor activities of these conjugates. The N(4)-ursodeoxycholic acid conjugate of cytarabine (compound 5) exhibited optimal stability (t1/2=90min) in vitro and a 3.9-fold prolonged half-life of cytarabine in vivo. More importantly, compound 5 increased the oral bioavailability 2-fold compared with cytarabine. The results of the present study suggest that the prodrug strategy based on the bile acid transporters is suitable for improving the oral absorption and the clinical application of cytarabine. PMID:27377011

  20. Design of Large Momentum Acceptance Transport Systems

    SciTech Connect

    D.R. Douglas

    2005-05-01

    The use of energy recovery to enable high power linac operation often gives rise to an attendant challenge--the transport of high power beams subtending large phase space volumes. In particular applications--such as FEL driver accelerators--this manifests itself as a requirement for beam transport systems with large momentum acceptance. We will discuss the design, implementation, and operation of such systems. Though at times counterintuitive in behavior (perturbative descriptions may, for example, be misleading), large acceptance systems have been successfully utilized for generations as spectrometers and accelerator recirculators [1]. Such systems are in fact often readily designed using appropriate geometric descriptions of beam behavior; insight provided using such a perspective may in addition reveal inherent symmetries that simplify construction and improve operability. Our discussion will focus on two examples: the Bates-clone recirculator used in the Jefferson Lab 10 kW IR U pgrade FEL (which has an observed acceptance of 10% or more) and a compaction-managed mirror-bend achromat concept with an acceptance ranging from 50 to 150 MeV.

  1. Auxin Transport in Zea mays Coleoptiles II. Influence of Light on the Transport of Indoleacetic Acid-2-14C

    PubMed Central

    Naqvi, S. M.; Gordon, S. A.

    1967-01-01

    The effect of bilateral irradiation with white light (1000 Meter Candle Sec) on the basipetal transport of auxin has been investigated. Illumination of either the intact shoot or the excised coleoptile tip of the Zea seedling, decreased the amount of diffusible auxin obtained from the tip, and decreased Avena curvature response to unilaterally applied indoleacetic acid. Irradiation of the intact Zea seedling did not affect the absorption of 14C-labeled indoleacetic acid from an agar block subsequently placed on the decapitated coleoptile. However, light caused a significant decrease in the amount of labeled auxin basipetally transported, without affecting materially the velocity of that transport. These and other observations are interpreted as support for the hypothesis that the primary hormonal phenomenon in first-positive phototropism is a light-induced impairment in the basipetal transport of auxin. PMID:16656477

  2. Increased ubiquitination and reduced plasma membrane trafficking of placental amino acid transporter SNAT-2 in human IUGR.

    PubMed

    Chen, Yi-Yung; Rosario, Fredrick J; Shehab, Majida Abu; Powell, Theresa L; Gupta, Madhulika B; Jansson, Thomas

    2015-12-01

    Placental amino acid transport is decreased in intrauterine growth restriction (IUGR); however, the underlying mechanisms remain largely unknown. We have shown that mechanistic target of rapamycin (mTOR) signalling regulates system A amino acid transport by modulating the ubiquitination and plasma membrane trafficking of sodium-coupled neutral amino acid transporter 2 (SNAT-2) in cultured primary human trophoblast cells. We hypothesize that IUGR is associated with (1) inhibition of placental mTORC1 and mTORC2 signalling pathways, (2) increased amino acid transporter ubiquitination in placental homogenates and (3) decreased protein expression of SNAT-2 in the syncytiotrophoblast microvillous plasma membrane (MVM). To test this hypothesis, we collected placental tissue and isolated MVM from women with pregnancies complicated by IUGR (n=25) and gestational age-matched women with appropriately grown control infants (n=19, birth weights between the twenty-fifth to seventy-fifth percentiles). The activity of mTORC1 and mTORC2 was decreased whereas the protein expression of the ubiquitin ligase NEDD4-2 (neural precursor cell expressed developmentally down-regulated protein 4-2; +72%, P<0.0001) and the ubiquitination of SNAT-2 (+180%, P<0.05) were increased in homogenates of IUGR placentas. Furthermore, IUGR was associated with decreased system A amino acid transport activity (-72%, P<0.0001) and SNAT-1 (-42%, P<0.05) and SNAT-2 (-31%, P<0.05) protein expression in MVM. In summary, these findings are consistent with the possibility that decreased placental mTOR activity causes down-regulation of placental system A activity by shifting SNAT-2 trafficking towards proteasomal degradation, thereby contributing to decreased fetal amino acid availability and restricted fetal growth in IUGR. PMID:26374858

  3. Metal transport in a stream polluted by acid mine drainage--The Afon Goch, Anglesey, UK.

    PubMed

    Boult, S; Collins, D N; White, K N; Curtis, C D

    1994-01-01

    Sampling of the Afon Goch over a 14-month period revealed maximum dissolved Fe, Al, Mn, Cu and Zn concentrations of 259, 167, 49, 60 and 42 mg dm(-3), respectively, and pH as low as 2.3, making it one of the most metal- and acid-contaminated streams in the UK. The river produces particulates by precipitation of ferrihydrite, due to the entry of near-neutral tributary waters, under all discharge conditions. Consequently, metal transport in this stream is dominated by processes different from those in less contaminated streams. The stream acts as a sink for contaminants, except under high discharge, when accumulated metals are flushed from the system. The implications of these observations for the monitoring and management of streams polluted by acid mine drainage are discussed. PMID:15091699

  4. Mitochondrial ascorbic acid transport is mediated by a low-affinity form of the sodium-coupled ascorbic acid transporter-2.

    PubMed

    Muñoz-Montesino, Carola; Roa, Francisco J; Peña, Eduardo; González, Mauricio; Sotomayor, Kirsty; Inostroza, Eveling; Muñoz, Carolina A; González, Iván; Maldonado, Mafalda; Soliz, Carlos; Reyes, Alejandro M; Vera, Juan Carlos; Rivas, Coralia I

    2014-05-01

    Despite the fundamental importance of the redox metabolism of mitochondria under normal and pathological conditions, our knowledge regarding the transport of vitamin C across mitochondrial membranes remains far from complete. We report here that human HEK-293 cells express a mitochondrial low-affinity ascorbic acid transporter that molecularly corresponds to SVCT2, a member of the sodium-coupled ascorbic acid transporter family 2. The transporter SVCT1 is absent from HEK-293 cells. Confocal colocalization experiments with anti-SVCT2 and anti-organelle protein markers revealed that most of the SVCT2 immunoreactivity was associated with mitochondria, with minor colocalization at the endoplasmic reticulum and very low immunoreactivity at the plasma membrane. Immunoblotting of proteins extracted from highly purified mitochondrial fractions confirmed that SVCT2 protein was associated with mitochondria, and transport analysis revealed a sigmoidal ascorbic acid concentration curve with an apparent ascorbic acid transport Km of 0.6mM. Use of SVCT2 siRNA for silencing SVCT2 expression produced a major decrease in mitochondrial SVCT2 immunoreactivity, and immunoblotting revealed decreased SVCT2 protein expression by approximately 75%. Most importantly, the decreased protein expression was accompanied by a concomitant decrease in the mitochondrial ascorbic acid transport rate. Further studies using HEK-293 cells overexpressing SVCT2 at the plasma membrane revealed that the altered kinetic properties of mitochondrial SVCT2 are due to the ionic intracellular microenvironment (low in sodium and high in potassium), with potassium acting as a concentration-dependent inhibitor of SVCT2. We discarded the participation of two glucose transporters previously described as mitochondrial dehydroascorbic acid transporters; GLUT1 is absent from mitochondria and GLUT10 is not expressed in HEK-293 cells. Overall, our data indicate that intracellular SVCT2 is localized in mitochondria, is

  5. Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures.

    PubMed

    Liu, Jie; Lu, Hong; Lu, Yuan-Fu; Lei, Xiaohong; Cui, Julia Yue; Ellis, Ewa; Strom, Stephen C; Klaassen, Curtis D

    2014-10-01

    Bile acids (BAs) are known to regulate their own homeostasis, but the potency of individual bile acids is not known. This study examined the effects of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) on expression of BA synthesis and transport genes in human primary hepatocyte cultures. Hepatocytes were treated with the individual BAs at 10, 30, and 100μM for 48 h, and RNA was extracted for real-time PCR analysis. For the classic pathway of BA synthesis, BAs except for UDCA markedly suppressed CYP7A1 (70-95%), the rate-limiting enzyme of bile acid synthesis, but only moderately (35%) down-regulated CYP8B1 at a high concentration of 100μM. BAs had minimal effects on mRNA of two enzymes of the alternative pathway of BA synthesis, namely CYP27A1 and CYP7B1. BAs increased the two major target genes of the farnesoid X receptor (FXR), namely the small heterodimer partner (SHP) by fourfold, and markedly induced fibroblast growth factor 19 (FGF19) over 100-fold. The BA uptake transporter Na(+)-taurocholate co-transporting polypeptide was unaffected, whereas the efflux transporter bile salt export pump was increased 15-fold and OSTα/β were increased 10-100-fold by BAs. The expression of the organic anion transporting polypeptide 1B3 (OATP1B3; sixfold), ATP-binding cassette (ABC) transporter G5 (ABCG5; sixfold), multidrug associated protein-2 (MRP2; twofold), and MRP3 (threefold) were also increased, albeit to lesser degrees. In general, CDCA was the most potent and effective BA in regulating these genes important for BA homeostasis, whereas DCA and CA were intermediate, LCA the least, and UDCA ineffective.

  6. Sialic acid catabolism and transport gene clusters are lineage specific in Vibrio vulnificus.

    PubMed

    Lubin, Jean-Bernard; Kingston, Joseph J; Chowdhury, Nityananda; Boyd, E Fidelma

    2012-05-01

    Sialic or nonulosonic acids are nine-carbon alpha ketosugars that are present in all vertebrate mucous membranes. Among bacteria, the ability to catabolize sialic acid as a carbon source is present mainly in pathogenic and commensal species of animals. Previously, it was shown that several Vibrio species carry homologues of the genes required for sialic acid transport and catabolism, which are genetically linked. In Vibrio cholerae on chromosome I, these genes are carried on the Vibrio pathogenicity island-2 region, which is confined to pathogenic isolates. We found that among the three sequenced Vibrio vulnificus clinical strains, these genes are present on chromosome II and are not associated with a pathogenicity island. To determine whether the sialic acid transport (SAT) and catabolism (SAC) region is universally present within V. vulnificus, we examined 67 natural isolates whose phylogenetic relationships are known. We found that the region was present predominantly among lineage I of V. vulnificus, which is comprised mainly of clinical isolates. We demonstrate that the isolates that contain this region can catabolize sialic acid as a sole carbon source. Two putative transporters are genetically linked to the region in V. vulnificus, the tripartite ATP-independent periplasmic (TRAP) transporter SiaPQM and a component of an ATP-binding cassette (ABC) transporter. We constructed an in-frame deletion mutation in siaM, a component of the TRAP transporter, and demonstrate that this transporter is essential for sialic acid uptake in this species. Expression analysis of the SAT and SAC genes indicates that sialic acid is an inducer of expression. Overall, our study demonstrates that the ability to catabolize and transport sialic acid is predominately lineage specific in V. vulnificus and that the TRAP transporter is essential for sialic acid uptake.

  7. Chemically generated convective transport in microfluidic system

    NASA Astrophysics Data System (ADS)

    Shklyaev, Oleg; Das, Sambeeta; Altemose, Alicia; Shum, Henry; Balazs, Anna; Sen, Ayusman

    High precision manipulation of small volumes of fluid, containing suspended micron sized objects like cells, viruses, and large molecules, is one of the main goals in designing modern lab-on-a-chip devices which can find a variety of chemical and biological applications. To transport the cargo toward sensing elements, typical microfluidic devices often use pressure driven flows. Here, we propose to use enzymatic chemical reactions which decompose reagent into less dense products and generate flows that can transport particles. Density variations that lead to flow in the assigned direction are created between the place where reagent is fed into the solution and the location where it is decomposed by enzymes attached to the surface of the microchannel. When the reagent is depleted, the fluid motion stops and particles sediment to the bottom. We demonstrate how the choice of chemicals, leading to specific reaction rates, can affect the transport properties. In particular, we show that the intensity of the fluid flow, the final location of cargo, and the time for cargo delivery are controlled by the amount and type of reagent in the system.

  8. Saenger space transportation system - Progress report

    NASA Astrophysics Data System (ADS)

    Koelle, Dietrich E.; Kuczera, Heribert

    1992-10-01

    The first part of the Saenger System Definition Study within the German National Hypersonics Technology Program (1988 to 1992) was completed by mid-1990. This paper summarizes the progress made and the status of the project as of that milestone which was formally completed by the System Study Presentation in July 1990. For the second phase of the study (mid-1990 to end 1992) the original philosophy of different upper stages for manned space operations and for unmanned cargo/payloads transportation is being maintained, however, a winged unmanned Horus-C version has been found to be a better solution than the originally conceived expendable ballistic stage Cargus. The advantage of this twin-Horus Concept is the greater commonality of both upper stages as well as the new return capability of payloads up to 7 Mg. The maximum payload capability of the expendable stage was of course higher, but it is assumed that for larger payloads a complementary launch vehicle (i.e. Ariane 5) will be further available. The paper also presents new data about the Horus return flight trajectories as well as on the aerothermodynamic studies and experimental work. Finally, aspects of mission operations and economics are discussed which are of special importance for such an advanced reusable space transportation system.

  9. Conceptual design of a Mars transportation system

    NASA Technical Reports Server (NTRS)

    1992-01-01

    In conjunction with NASA Marshall Space Flight Center and several major aerospace corporations the University of Minnesota has developed a scenario to place humans on Mars by the year 2016. The project took the form of a year-long design course in the senior design curricula at the University's Aerospace Engineering and Mechanics Department. Students worked with the instructor, teaching assistants and engineers in industry to develop a vehicle and the associated mission profile to fulfill the requirements of the Mars Transportation System. This report is a summary of the final design and the process though which the final product was developed.

  10. A space transportation system operations model

    NASA Technical Reports Server (NTRS)

    Morris, W. Douglas; White, Nancy H.

    1987-01-01

    Presented is a description of a computer program which permits assessment of the operational support requirements of space transportation systems functioning in both a ground- and space-based environment. The scenario depicted provides for the delivery of payloads from Earth to a space station and beyond using upper stages based at the station. Model results are scenario dependent and rely on the input definitions of delivery requirements, task times, and available resources. Output is in terms of flight rate capabilities, resource requirements, and facility utilization. A general program description, program listing, input requirements, and sample output are included.

  11. Mars integrated transportation system multistage Mars mission

    NASA Technical Reports Server (NTRS)

    1991-01-01

    In accordance with the objective of the Mars Integrated Transport System (MITS) program, the Multistage Mars Mission (MSMM) design team developed a profile for a manned mission to Mars. The purpose of the multistage mission is to send a crew of five astronauts to the martian surface by the year 2019. The mission continues man's eternal quest for exploration of new frontiers. This mission has a scheduled duration of 426 days that includes experimentation en route as well as surface exploration and experimentation. The MSMM is also designed as a foundation for a continuing program leading to the colonization of the planet Mars.

  12. Space transportation system biomedical operations support study

    NASA Technical Reports Server (NTRS)

    White, S. C.

    1983-01-01

    The shift of the Space Transportation System (STS) flight tests of the orbiter vehicle to the preparation and flight of the payloads is discussed. Part of this change is the transition of the medical and life sciences aspects of the STS flight operations to reflect the new state. The medical operations, the life sciences flight experiments support requirements and the intramural research program expected to be at KSC during the operational flight period of the STS and a future space station are analyzed. The adequacy of available facilities, plans, and resources against these future needs are compared; revisions and/or alternatives where appropriate are proposed.

  13. Future Intelligent Transportation Systems and Sensors

    NASA Astrophysics Data System (ADS)

    Hosaka, Akio

    A road vehicle traffic contributes to the social improvement greatly, but it has big problems such as safety, congestion, environment, energy, elder people driving and adaptation to information society. ITS (Intelligent Transportation Systems) is expected as a direction solving these. The intellectual function about a road vehicle traffic depended on most of human beings. ITS helps intellectual functions such as information sensing, situation recognition, judgment, planning and operation. A sensor detecting information is an important key in ITS. I describe expectation to a sensor in ITS.

  14. Operating systems in the air transportation environment.

    NASA Technical Reports Server (NTRS)

    Cherry, G. W.

    1971-01-01

    Consideration of the problems facing air transport at present, and to be expected in the future. In the Northeast Corridor these problems involve community acceptance, airway and airport congestion and delays, passenger acceptance, noise reduction, and improvements in low-density short-haul economics. In the development of a superior short-haul operating system, terminal-configured vs cruise-configured vehicles are evaluated. CTOL, STOL, and VTOL aircraft of various types are discussed. In the field of noise abatement, it is shown that flight procedural techniques are capable of supplementing ?quiet engine' technology.

  15. National Space Transportation Systems Program mission report

    NASA Technical Reports Server (NTRS)

    Collins, M. A., Jr.; Aldrich, A. D.; Lunney, G. S.

    1984-01-01

    The STS 41-C National Space Transportation Systems Program Mission Report contains a summary of the major activities and accomplishments of the eleventh Shuttle flight and fifth flight of the OV-099 vehicle, Challenger. Also summarized are the significant problems that occurred during STS 41-C, and a problem tracking list that is a complete list of all problems that occurred during the flight. The major objectives of flight STS 41-C were to successfully deploy the LDEF (long duration exposure facility) and retrieve, repair and redeploy the SMM (Solar Maximum Mission) spacecraft, and perform functions of IMAX and Cinema 360 cameras.

  16. Fireworthiness of transport aircraft interior systems

    NASA Technical Reports Server (NTRS)

    Parker, J. A.; Kourtides, D. A.

    1981-01-01

    This paper presents an overview of certain aspects of the evaluation of the fireworthiness of transport aircraft interiors. First, it addresses the key materials question concerning the effect of interior systems on the survival of passengers and crew in the case of an uncontrolled fire. Second, it examines some technical opportunities that are available today through the modification of aircraft interior subsystem components, modifications that may reasonably by expected to provide improvements in aircraft fire safety. Cost and risk benefits still remain to be determined.

  17. The role of L-type amino acid transporter 1 in human tumors

    PubMed Central

    Zhao, Yu; Wang, Lin; Pan, Jihong

    2015-01-01

    Summary L-type amino acid transporter 1 (LAT1) is an L-type amino acid transporter and transports large neutral amino acids such as leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, methionine, and histidine. LAT1 was found to be highly expressed especially in human cancer tissues, and up-regulated LAT1 can lead to dysfunction in human tumor cells. These findings suggest that LAT1 plays an important role in human tumors. This review provides an overview of the current understanding of LAT1 expression and its clinical significance and function in tumors. PMID:26668776

  18. Structural basis of the alternating-access mechanism in a bile acid transporter

    NASA Astrophysics Data System (ADS)

    Zhou, Xiaoming; Levin, Elena J.; Pan, Yaping; McCoy, Jason G.; Sharma, Ruchika; Kloss, Brian; Bruni, Renato; Quick, Matthias; Zhou, Ming

    2014-01-01

    Bile acids are synthesized from cholesterol in hepatocytes and secreted through the biliary tract into the small intestine, where they aid in absorption of lipids and fat-soluble vitamins. Through a process known as enterohepatic recirculation, more than 90% of secreted bile acids are then retrieved from the intestine and returned to the liver for resecretion. In humans, there are two Na+-dependent bile acid transporters involved in enterohepatic recirculation, the Na+-taurocholate co-transporting polypeptide (NTCP; also known as SLC10A1) expressed in hepatocytes, and the apical sodium-dependent bile acid transporter (ASBT; also known as SLC10A2) expressed on enterocytes in the terminal ileum. In recent years, ASBT has attracted much interest as a potential drug target for treatment of hypercholesterolaemia, because inhibition of ASBT reduces reabsorption of bile acids, thus increasing bile acid synthesis and consequently cholesterol consumption. However, a lack of three-dimensional structures of bile acid transporters hampers our ability to understand the molecular mechanisms of substrate selectivity and transport, and to interpret the wealth of existing functional data. The crystal structure of an ASBT homologue from Neisseria meningitidis (ASBTNM) in detergent was reported recently, showing the protein in an inward-open conformation bound to two Na+ and a taurocholic acid. However, the structural changes that bring bile acid and Na+ across the membrane are difficult to infer from a single structure. To understand the structural changes associated with the coupled transport of Na+ and bile acids, here we solved two structures of an ASBT homologue from Yersinia frederiksenii (ASBTYf) in a lipid environment, which reveal that a large rigid-body rotation of a substrate-binding domain gives the conserved `crossover' region, where two discontinuous helices cross each other, alternating accessibility from either side of the cell membrane. This result has implications

  19. Third-order TRANSPORT: A computer program for designing charged particle beam transport systems

    SciTech Connect

    Carey, D.C.; Brown, K.L.; Rothacker, F.

    1995-05-01

    TRANSPORT has been in existence in various evolutionary versions since 1963. The present version of TRANSPORT is a first-, second-, and third-order matrix multiplication computer program intended for the design of static-magnetic beam transport systems. This report discusses the following topics on TRANSPORT: Mathematical formulation of TRANSPORT; input format for TRANSPORT; summaries of TRANSPORT elements; preliminary specifications; description of the beam; physical elements; other transformations; assembling beam lines; operations; variation of parameters for fitting; and available constraints -- the FIT command.

  20. Functional relationship between cationic amino acid transporters and beta-defensins: implications for dry skin diseases and the dry eye.

    PubMed

    Jäger, Kristin; Garreis, Fabian; Posa, Andreas; Dunse, Matthias; Paulsen, Friedrich P

    2010-04-20

    The ocular surface, constantly exposed to environmental pathogens, is particularly vulnerable to infection. Hence an advanced immune defence system is essential to protect the eye from microbial attack. Antimicrobial peptides, such as beta-defensins, are essential components of the innate immune system and are the first line of defence against invaders of the eye. High concentrations of L-arginine and L-lysine are necessary for the expression of beta-defensins. These are supplied by epithelial cells in inflammatory processes. The limiting factor for initiation of beta-defensin production is the transport of L-arginine and L-lysine into the cell. This transport is performed to 80% by only one transporter system in the human, the y(+)-transporter. This group of proteins exclusively transports the cationic amino acids L-arginine, L-lysine and L-ornithine and is also known under the term cationic amino acid transporter proteins (CAT-proteins). Various infections associated with L-arginine deficiency (for example psoriasis, keratoconjuctivitis sicca) are also associated with an increase in beta-defensin production. For the first time, preliminary work has shown the expression of human CATs in ocular surface epithelia and tissues of the lacrimal apparatus indicating their relevance for diseases of the ocular surface. In this review, we summarize current knowledge on the human CATs that appear to be integrated in causal regulation cascades of beta-defensins, thereby offering novel concepts for therapeutic perspectives.

  1. A study of characteristics of intercity transportation systems. Phase 1: Definition of transportation comparison methodology

    NASA Technical Reports Server (NTRS)

    English, J. M.; Smith, J. L.; Lifson, M. W.

    1978-01-01

    The objectives of this study are: (1) to determine a unified methodological framework for the comparison of intercity passenger and freight transportation systems; (2) to review the attributes of existing and future transportation systems for the purpose of establishing measures of comparison. These objectives were made more specific to include: (1) development of a methodology for comparing long term transportation trends arising from implementation of various R&D programs; (2) definition of value functions and attribute weightings needed for further transportation goals.

  2. Risk management model in road transport systems

    NASA Astrophysics Data System (ADS)

    Sakhapov, R. L.; Nikolaeva, R. V.; Gatiyatullin, M. H.; Makhmutov, M. M.

    2016-08-01

    The article presents the results of a study of road safety indicators that influence the development and operation of the transport system. Road safety is considered as a continuous process of risk management. Authors constructed a model that relates the social risks of a major road safety indicator - the level of motorization. The model gives a fairly accurate assessment of the level of social risk for any given level of motorization. Authors calculated the dependence of the level of socio-economic costs of accidents and injured people in them. The applicability of the concept of socio-economic damage is caused by the presence of a linear relationship between the natural and economic indicators damage from accidents. The optimization of social risk is reduced to finding the extremum of the objective function that characterizes the economic effect of the implementation of measures to improve safety. The calculations make it possible to maximize the net present value, depending on the costs of improving road safety, taking into account socio-economic damage caused by accidents. The proposed econometric models make it possible to quantify the efficiency of the transportation system, allow to simulate the change in road safety indicators.

  3. Innovative technology summary report: Transportable vitrification system

    SciTech Connect

    1998-09-01

    At the end of the cold war, many of the Department of Energy`s (DOE`s) major nuclear weapons facilities refocused their efforts on finding technically sound, economic, regulatory compliant, and stakeholder acceptable treatment solutions for the legacy of mixed wastes they had produced. In particular, an advanced stabilization process that could effectively treat the large volumes of settling pond and treatment sludges was needed. Based on this need, DOE and its contractors initiated in 1993 the EM-50 sponsored development effort required to produce a deployable mixed waste vitrification system. As a consequence, the Transportable Vitrification System (TVS) effort was undertaken with the primary requirement to develop and demonstrate the technology and associated facility to effectively vitrify, for compliant disposal, the applicable mixed waste sludges and solids across the various DOE complex sites. After 4 years of development testing with both crucible and pilot-scale melters, the TVS facility was constructed by Envitco, evaluated and demonstrated with surrogates, and then successfully transported to the ORNL ETTP site and demonstrated with actual mixed wastes in the fall of 1997. This paper describes the technology, its performance, the technology applicability and alternatives, cost, regulatory and policy issues, and lessons learned.

  4. Sensor system for fuel transport vehicle

    DOEpatents

    Earl, Dennis Duncan; McIntyre, Timothy J.; West, David L.

    2016-03-22

    An exemplary sensor system for a fuel transport vehicle can comprise a fuel marker sensor positioned between a fuel storage chamber of the vehicle and an access valve for the fuel storage chamber of the vehicle. The fuel marker sensor can be configured to measure one or more characteristics of one or more fuel markers present in the fuel adjacent the sensor, such as when the marked fuel is unloaded at a retail station. The one or more characteristics can comprise concentration and/or identity of the one or more fuel markers in the fuel. Based on the measured characteristics of the one or more fuel markers, the sensor system can identify the fuel and/or can determine whether the fuel has been adulterated after the marked fuel was last measured, such as when the marked fuel was loaded into the vehicle.

  5. Transport systems research vehicle color display system operations manual

    NASA Technical Reports Server (NTRS)

    Easley, Wesley C.; Johnson, Larry E.

    1989-01-01

    A recent upgrade of the Transport Systems Research Vehicle operated by the Advanced Transport Operating Systems Program Office at the NASA Langley Research Center has resulted in an all-glass panel in the research flight deck. Eight ARINC-D size CRT color displays make up the panel. A major goal of the display upgrade effort was ease of operation and maintenance of the hardware while maintaining versatility needed for flight research. Software is the key to this required versatility and will be the area demanding the most detailed technical design expertise. This document is is intended to serve as a single source of quick reference information needed for routine operation and system level maintenance. Detailed maintenance and modification of the display system will require specific design documentation and must be accomplished by individuals with specialized knowledge and experience.

  6. Transporters for ammonium, amino acids and peptides are expressed in pitchers of the carnivorous plant Nepenthes.

    PubMed

    Schulze, W; Frommer, W B; Ward, J M

    1999-03-01

    Insect capture and digestion contribute substantially to the nitrogen budget of carnivorous plants. In Nepenthes, insect-derived nitrogenous compounds are imported from the pitcher fluid and transported throughout the plant via the vascular tissue to support growth. Import and distribution of nutrients may require transmembrane nitrogen transporters. Representatives of three classes of genes encoding transporters for the nitrogenous compounds ammonium, amino acids and peptides were identified in Nepenthes pitchers. The expression at the cellular level of an ammonium transporter gene, three amino acid transporter genes, and one peptide transporter gene were investigated in the insect trapping organs of Nepenthes. Expression of the ammonium transporter gene NaAMT1 was detected in the head cells of digestive glands in the lower part of the pitcher where NaAMT1 may function in ammonium uptake from the pitcher fluid. One amino acid transporter gene, NaAAP1, was expressed in bundle sheath cells surrounding the vascular tissue. To understand the locations where transmembrane transport could be required within the pitcher, symplasmic and apoplasmic continuity was probed using fluorescent dyes. Symplasmic connections were not found between cortical cells and vascular bundles. Therefore, the amino acid transporter encoded by NaAAP1 may be involved in transport of amino acids into the vascular tissue. In contrast, expression of the peptide transporter gene NaNTR1 was detected in phloem cells of the vascular tissue within pitchers. NaNTR1 may function in the export of nitrogen from the pitcher by loading peptides into the phloem. PMID:10230062

  7. Air support facilities. [interface between air and surface transportation systems

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Airports are discussed in terms of the interface between the ground and air for transportation systems. The classification systems, design, facilities, administration, and operations of airports are described.

  8. A study of characteristics of intercity transportation systems. Phase 1: Definition of transportation comparison methodology

    NASA Technical Reports Server (NTRS)

    English, J. M.; Smith, J. L.; Lifson, M. W.

    1978-01-01

    Decision making in early transportation planning must be responsive to complex value systems representing various policies and objectives. The assessment of alternative transportation concepts during the early initial phases of the system life cycle, when supportive research and technology development activities are defined, requires estimates of transportation, environmental, and socio-economic impacts throughout the system life cycle, which is a period of some 40 or 50 years. A unified methodological framework for comparing intercity passenger and freight transportation systems is described and is extended to include the comparison of long term transportation trends arising from implementation of the various R & D programs. The attributes of existing and future transportation systems are reviewed in order to establish measures for comparison, define value functions, and attribute weightings needed for comparing alternative policy actions for furthering transportation goals. Comparison criteria definitions and an illustrative example are included.

  9. 21 CFR 862.1450 - Lactic acid test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....1450 Lactic acid test system. (a) Identification. A lactic acid test system is a device intended to measure lactic acid in whole blood and plasma. Lactic acid measurements that evaluate the acid-base status... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Lactic acid test system. 862.1450 Section...

  10. 21 CFR 862.1450 - Lactic acid test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....1450 Lactic acid test system. (a) Identification. A lactic acid test system is a device intended to measure lactic acid in whole blood and plasma. Lactic acid measurements that evaluate the acid-base status... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lactic acid test system. 862.1450 Section...

  11. 21 CFR 862.1450 - Lactic acid test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ....1450 Lactic acid test system. (a) Identification. A lactic acid test system is a device intended to measure lactic acid in whole blood and plasma. Lactic acid measurements that evaluate the acid-base status... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lactic acid test system. 862.1450 Section...

  12. 21 CFR 862.1450 - Lactic acid test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....1450 Lactic acid test system. (a) Identification. A lactic acid test system is a device intended to measure lactic acid in whole blood and plasma. Lactic acid measurements that evaluate the acid-base status... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Lactic acid test system. 862.1450 Section...

  13. Convective heat transport in geothermal systems

    SciTech Connect

    Lippmann, M.J.; Bodvarsson, G.S.

    1986-08-01

    Most geothermal systems under exploitation for direct use or electrical power production are of the hydrothermal type, where heat is transferred essentially by convection in the reservoir, conduction being secondary. In geothermal systems, buoyancy effects are generally important, but often the fluid and heat flow patterns are largely controlled by geologic features (e.g., faults, fractures, continuity of layers) and location of recharge and discharge zones. During exploitation, these flow patterns can drastically change in response to pressure and temperature declines, and changes in recharge/discharge patterns. Convective circulation models of several geothermal systems, before and after start of fluid production, are described, with emphasis on different characteristics of the systems and the effects of exploitation on their evolution. Convective heat transport in geothermal fields is discussed, taking into consideration (1) major geologic features; (2) temperature-dependent rock and fluid properties; (3) fracture- versus porous-medium characteristics; (4) single- versus two-phase reservoir systems; and (5) the presence of noncondensible gases.

  14. Road Transportable Analytical Laboratory system. Phase 1

    SciTech Connect

    Finger, S.M.; Keith, V.F.; Spertzel, R.O.; De Avila, J.C.; O`Donnell, M.; Vann, R.L.

    1993-09-01

    This developmental effort clearly shows that a Road Transportable Analytical Laboratory System is a worthwhile and achievable goal. The RTAL is designed to fully analyze (radioanalytes, and organic and inorganic chemical analytes) 20 samples per day at the highest levels of quality assurance and quality control. It dramatically reduces the turnaround time for environmental sample analysis from 45 days (at a central commercial laboratory) to 1 day. At the same time each RTAL system will save the DOE over $12 million per year in sample analysis costs compared to the costs at a central commercial laboratory. If RTAL systems were used at the eight largest DOE facilities (at Hanford, Savannah River, Fernald, Oak Ridge, Idaho, Rocky Flats, Los Alamos, and the Nevada Test Site), the annual savings would be $96,589,000. The DOE`s internal study of sample analysis needs projects 130,000 environmental samples requiring analysis in FY 1994, clearly supporting the need for the RTAL system. The cost and time savings achievable with the RTAL system will accelerate and improve the efficiency of cleanup and remediation operations throughout the DOE complex.

  15. Future space transportation system architecture avionics requirements

    NASA Astrophysics Data System (ADS)

    Stone, Howard; Engelund, Walt

    1993-12-01

    NASA began a multi-center study in January 1993 to examine options for providing the most cost effective space transportation system in the future. The key advanced avionics requirements for these vehicle concepts are envisioned to provide significantly improved operational efficiency and effectiveness. It is very desirable to have adaptive guidance, navigation, and control approaches that will allow launch and return in almost any weather condition. The vehicles must be able to accommodate atmospheric density variations and winds without software changes. The flight operations must become much more autonomous in all flight regimes like an aircraft, and preflight checkout should make use of the onboard systems. When the vehicle returns to the launch site, subsystem health must be known and maintenance tasks scheduled accordingly. Ground testing of most subsystems must be eliminated. Also, the health monitoring system must be designed to enhance the ability to abort the mission significantly and save the crew and the vehicle. The displays and controls must be much less complex than current systems and must significantly reduce pilot work load. It is important to have low power, light weight displays and controls. Rendezvous and docking and all flight phases must have autopilot capability to reduce pilot work load for routine operations and in abort situations. The vehicles must have the demonstrated ability to return to the launch site. Abort from all mission phases can put additional demands on the communications system.

  16. Characterization and Regulation of the Amino Acid Transporter SNAT2 in the Small Intestine of Piglets.

    PubMed

    Li, Guangran; Li, Jianjun; Tan, Bie; Wang, Jing; Kong, Xiangfeng; Guan, Guiping; Li, Fengna; Yin, Yulong

    2015-01-01

    The sodium-dependent neutral amino acid transporter 2 (SNAT2), which has dual transport/receptor functions, is well documented in eukaryotes and some mammalian systems, but has not yet been verified in piglets. The objective of this study was to investigate the characteristics and regulation of SNAT2 in the small intestine of piglets. The 1,521-bp porcine full cDNA sequence of SNAT2 (KC769999) from the small intestine of piglets was cloned. The open reading frame of cDNA encodes 506 deduced amino acid residues with a calculated molecular mass of 56.08 kDa and an isoelectric point (pI) of 7.16. Sequence alignment and phylogenetic analysis revealed that SNAT2 is highly evolutionarily conserved in mammals. SNAT2 mRNA can be detected in the duodenum, jejunum and ileum by real-time quantitative PCR. During the suckling period from days 1 to 21, the duodenum had the highest abundance of SNAT2 mRNA among the three segments of the small intestine. There was a significant decrease in the expression of SNAT2 mRNA in the duodenal and jejunal mucosa and in the expression of SNAT2 protein in the jejunal and ileal mucosa on day 1 after weaning (P < 0.05). Studies with enterocytes in vitro showed that amino acid starvation and supplementation with glutamate, arginine or leucine enhanced, while supplementation with glutamine reduced, SNAT2 mRNA expression (P < 0.05). These results regarding the characteristics and regulation of SNAT2 should help to provide some information to further clarify its roles in the absorption of amino acids and signal transduction in the porcine small intestine.

  17. Essential amino acid transporter Lat4 (Slc43a2) is required for mouse development

    PubMed Central

    Guetg, Adriano; Mariotta, Luca; Bock, Lukas; Herzog, Brigitte; Fingerhut, Ralph; Camargo, Simone M R; Verrey, François

    2015-01-01

    side of small intestine enterocytes and kidney epithelial cells of the proximal tubule, thick ascending limb and distal convoluted tubule. In the Xenopus oocyte expression system, Lat4 is shown to function as a uniporter with symmetric intracellular and extracellular apparent affinities for phenylalanine. Mice lacking Lat4 display a slight intrauterine growth restriction, postnatal malnutrition and early death, presumably as a result of defective amino acid (re)absorption. These results demonstrate the crucial role that the uniporter Lat4 plays for amino acid transport across cellular barriers and mouse development. PMID:25480797

  18. Regulation of amino acid transporters in pluripotent cell populations in the embryo and in culture; novel roles for sodium-coupled neutral amino acid transporters.

    PubMed

    Tan, Boon Siang Nicholas; Rathjen, Peter D; Harvey, Alexandra J; Gardner, David K; Rathjen, Joy

    2016-08-01

    The developmental outcomes of preimplantation mammalian embryos are regulated directly by the surrounding microenvironment, and inappropriate concentrations of amino acids, or the loss of amino acid-sensing mechanisms, can be detrimental and impact further development. A specific role for l-proline in the differentiation of embryonic stem (ES) cells, a cell population derived from the blastocyst, has been shown in culture. l-proline acts as a signalling molecule, exerting its effects through cell uptake and subsequent metabolism. Uptake in ES cells occurs predominantly through the sodium-coupled neutral amino acid transporter 2, Slc38a2 (SNAT2). Dynamic expression of amino acid transporters has been shown in the early mammalian embryo, reflecting functional roles for amino acids in embryogenesis. The expression of SNAT2 and family member Slc38a1 (SNAT1) was determined in mouse embryos from the 2-cell stage through to the early post-implantation pre-gastrulation embryo. Key changes in expression were validated in cell culture models of development. Both transporters showed temporal dynamic expression patterns and changes in intracellular localisation as differentiation progressed. Changes in transporter expression likely reflect different amino acid requirements during development. Findings include the differential expression of SNAT1 in the inner and outer cells of the compacted morula and nuclear localisation of SNAT2 in the trophectoderm and placental lineages. Furthermore, SNAT2 expression was up-regulated in the epiblast prior to primitive ectoderm formation, an expression pattern consistent with a role for the transporter in later developmental decisions within the pluripotent lineage. We propose that the differential expression of SNAT2 in the epiblast provides evidence for an l-proline-mediated mechanism contributing to the regulation of embryonic development. PMID:27373508

  19. mRNA expression of amino acid transporters, aminopeptidase, and the di- and tri-peptide transporter PepT1 in the intestine and liver of posthatch broiler chicks.

    PubMed

    Miska, Katarzyna B; Fetterer, Raymond H; Wong, Eric A

    2015-06-01

    Amino acid (AA) transporter proteins are responsible for the movement of amino acids in and out of cells. Aminopeptidase cleaves AAs from the N-terminus of polypeptides making them available for transport, while PepT1 is a di- and tripeptide transporter. In the intestine, these proteins are present on the brush border and basolateral membranes of enterocytes, and are essential for the uptake of AAs into enterocytes and their release into circulation. The purpose of this study was to determine the level of transcription of these genes after hatch in 3 regions of the small intestine, the ceca, and liver. Heritage broiler chicks (n=5) were sampled at day after hatch and days 3, 5, 7, 10, 12, 14, 17, and 21 posthatch, and mRNA expression level was measured using absolute quantitation. The small intestine (duodenum, jejunum, and ileum) expressed the largest quantities of each gene tested. The expression in the ceca and liver was 1 to 3 orders of magnitude less than that of the small intestine. The expression of basolateral transporters in the small intestine was more constant over days posthatch than the expression of brush border transporters. In the ceca the expression of the brush border transporters decreased over the sampling period, while expression of basolateral genes was relatively constant. In the liver the expression of Na+ independent cationic and zwitterionic amino acid transporter (bo,+AT), Na+ independent cationic amino acid transporter 2 (CAT2), excitatory amino acid transporter 3 (EAAT3), and the heavy chain corresponding to the bo,+) system (rBAT) significantly decreased at 12 days posthatch; however, the expression of Na+ independent cationic and Na+ dependent neutral amino acid transporter 1 (y+LAT1), Na+ coupled neutral amino acid transporter 1; (SNAT1), and Na+ coupled neutral amino acid transporter 2 (SNAT2) significantly increased at day 5 posthatch compared to day 1 and these levels remained throughout the rest of the sampling period. The

  20. Proton transport in triflic acid pentahydrate studied via ab initio path integral molecular dynamics.

    PubMed

    Hayes, Robin L; Paddison, Stephen J; Tuckerman, Mark E

    2011-06-16

    Trifluoromethanesulfonic acid hydrates provide a well-defined system to study proton dissociation and transport in perfluorosulfonic acid membranes, typically used as the electrolyte in hydrogen fuel cells, in the limit of minimal water. The triflic acid pentahydrate crystal (CF(3)SO(3)H·5H(2)O) is sufficiently aqueous that it contains an extended three-dimensional water network. Despite it being extended, however, long-range proton transport along the network is structurally unfavorable and would require considerable rearrangement. Nevertheless, the triflic acid pentahydrate crystal system can provide a clear picture of the preferred locations of local protonic defects in the water network, which provides insights about related structures in the disordered, low-hydration environment of perfluorosulfonic acid membranes. Ab initio molecular dynamics simulations reveal that the proton defect is most likely to transfer to the closest water that has the expected presolvation and only contains water in its first solvation shell. Unlike the tetrahydrate of triflic acid (CF(3)SO(3)H·4H(2)O), there is no evidence of the proton preferentially transferring to a water molecule bridging two of the sulfonate groups. However, this could be an artifact of the crystal structure since the only such water molecule is separated from the proton by long O-O distances. Hydrogen bonding criteria, using the two-dimensional potential of mean force, are extracted. Radial distribution functions, free energy profiles, radii of gyration, and the root-mean-square displacement computed from ab initio path integral molecular dynamics simulations reveal that quantum effects do significantly extend the size of the protonic defect and increase the frequency of proton transfer events by nearly 15%. The calculated IR spectra confirm that the dominant protonic defect mostly exists as an Eigen cation but contains some Zundel ion characteristics. Chain lengths and ring sizes determined from the

  1. Characteristics of the transport of ascorbic acid into leucocytes

    SciTech Connect

    Raghoebar, M.; Huisman, J.A.M.; van den Berg, W.B.; van Ginneken, C.A.M.

    1987-02-02

    The degree and the mode of association of (/sup 14/C)-ascorbic acid with leucocytes are examined. The degree of association of ascorbic acid with polymorphonuclear leucocytes (1-3 %) is dependent on cell type, extracellular concentration of ascorbic acid, incubation temperature, intactness of the cells and the extracellular pH. All experiments are performed according to strict protocols as these compounds are labile in aqueous solutions. Further it is noticed that in all experiments an outward gradient of leucocyte endogenic ascorbic acid exists. The results suggest that the association process comprises at least one saturable pathway. The activation of polymorphonuclear leucocytes by phorbol myristate acetate increases the accumulation of ascorbic acid threefold. 30 references, 7 figures, 3 tables.

  2. Report on Bureau of Pupil Transportation Contract Busing System.

    ERIC Educational Resources Information Center

    Savitz, Reuven; And Others

    This report outlines the process and events related to the implementation of a new student bus transportation contract system for New York City schools and presents data on numbers of vehicles used, number of students transported, and costs. The revised system, which sought to attract new companies to the school bus transportation business, is…

  3. Modulating effect of ascorbic Acid on transport-induced immunosuppression in goats.

    PubMed

    Minka, Ndazo Salka; Ayo, Joseph Olusegun

    2011-01-01

    The effect of 12 h road transportation on some basic blood cells and the modulating role of ascorbic acid were investigated in 40 adult Red Sokoto goats during the hot dry season. The animals were divided into two groups, GI (experimental; n = 20) and GII (control; n = 20). Group 1 was administered with ascorbic acid (AA) per os at a dosage rate of 100 mg/kg body weight, while GII was given 10 mL of sterile water per goat. Forty minutes after the administration and loading, the goats were transported for 12 h. The result obtained in GII goats showed that loading, transportation, high ambient temperature (AT), and relative humidity (RH) encountered during transportation induced lymphopenia, neutrophilia, and eosinopenia, which can cause immunosuppression. In GI goats, the administration of AA prior to loading and transportation ameliorated the adverse effects of loading and transportation stress on neutrophil/lymphocyte ratio and eosinopenia of the goats.

  4. Code System To Analyze Radiological Impact From Radwaste Transportation.

    1988-05-01

    Version 00 RADSHIP-2 is a computer code system used to analyze the environmental impact of radwaste transportation in Taiwan. The specific transport scheme including the land transport by truck and sea transport by ship or barge were considered in the analysis for normal transport and transport accident conditions. The code combines meteorological, population, health physics, transportation, packaging and material factors and has the capability to obtain the results of the expected annual population radiation exposure,more » the expected number of annual latent cancer fatalities and the annual probability of a given number of early fatalities.« less

  5. Simulation framework for intelligent transportation systems

    SciTech Connect

    Ewing, T.; Doss, E.; Hanebutte, U.; Tentner, A.

    1996-10-01

    A simulation framework has been developed for a large-scale, comprehensive, scaleable simulation of an Intelligent Transportation System (ITS). The simulator is designed for running on parallel computers and distributed (networked) computer systems, but can run on standalone workstations for smaller simulations. The simulator currently models instrumented smart vehicles with in-vehicle navigation units capable of optimal route planning and Traffic Management Centers (TMC). The TMC has probe vehicle tracking capabilities (display position and attributes of instrumented vehicles), and can provide two-way interaction with traffic to provide advisories and link times. Both the in-vehicle navigation module and the TMC feature detailed graphical user interfaces to support human-factors studies. Realistic modeling of variations of the posted driving speed are based on human factors studies that take into consideration weather, road conditions, driver personality and behavior, and vehicle type. The prototype has been developed on a distributed system of networked UNIX computers but is designed to run on parallel computers, such as ANL`s IBM SP-2, for large-scale problems. A novel feature of the approach is that vehicles are represented by autonomous computer processes which exchange messages with other processes. The vehicles have a behavior model which governs route selection and driving behavior, and can react to external traffic events much like real vehicles. With this approach, the simulation is scaleable to take advantage of emerging massively parallel processor (MPP) systems.

  6. NASA's advanced space transportation system launch vehicles

    NASA Technical Reports Server (NTRS)

    Branscome, Darrell R.

    1991-01-01

    Some insight is provided into the advanced transportation planning and systems that will evolve to support long term mission requirements. The general requirements include: launch and lift capacity to low earth orbit (LEO); space based transfer systems for orbital operations between LEO and geosynchronous equatorial orbit (GEO), the Moon, and Mars; and Transfer vehicle systems for long duration deep space probes. These mission requirements are incorporated in the NASA Civil Needs Data Base. To accomplish these mission goals, adequate lift capacity to LEO must be available: to support science and application missions; to provide for construction of the Space Station Freedom; and to support resupply of personnel and supplies for its operations. Growth in lift capacity must be time phased to support an expanding mission model that includes Freedom Station, the Mission to Planet Earth, and an expanded robotic planetary program. The near term increase in cargo lift capacity associated with development of the Shuttle-C is addressed. The joint DOD/NASA Advanced Launch System studies are focused on a longer term new cargo capability that will significantly reduce costs of placing payloads in space.

  7. Receptor-transporter interactions of canonical ATP-binding cassette import systems in prokaryotes.

    PubMed

    Schneider, Erwin; Eckey, Viola; Weidlich, Daniela; Wiesemann, Nicole; Vahedi-Faridi, Ardeshir; Thaben, Paul; Saenger, Wolfram

    2012-04-01

    ATP-binding cassette (ABC) transport systems mediate the translocation of solutes across biological membranes at the expense of ATP. They share a common modular architecture comprising two pore-forming transmembrane domains and two nucleotide binding domains. In prokaryotes, ABC transporters are involved in the uptake of a large variety of chemicals, including nutrients, osmoprotectants and signal molecules. In pathogenic bacteria, some ABC importers are virulence factors. Canonical ABC import systems require an additional component, a substrate-specific receptor or binding protein for function. Interaction of the liganded receptor with extracytoplasmic loop regions of the transmembrane domains initiate the transport cycle. In this review we summarize the current knowledge on receptor-transporter interplay provided by crystal structures as well as by biochemical and biophysical means. In particular, we focus on the maltose/maltodextrin transporter of enterobacteria and the transporters for positively charged amino acids from the thermophile Geobacillus stearothermophilus and Salmonella enterica serovar Typhimurium. PMID:21561685

  8. Receptor-transporter interactions of canonical ATP-binding cassette import systems in prokaryotes.

    PubMed

    Schneider, Erwin; Eckey, Viola; Weidlich, Daniela; Wiesemann, Nicole; Vahedi-Faridi, Ardeshir; Thaben, Paul; Saenger, Wolfram

    2012-04-01

    ATP-binding cassette (ABC) transport systems mediate the translocation of solutes across biological membranes at the expense of ATP. They share a common modular architecture comprising two pore-forming transmembrane domains and two nucleotide binding domains. In prokaryotes, ABC transporters are involved in the uptake of a large variety of chemicals, including nutrients, osmoprotectants and signal molecules. In pathogenic bacteria, some ABC importers are virulence factors. Canonical ABC import systems require an additional component, a substrate-specific receptor or binding protein for function. Interaction of the liganded receptor with extracytoplasmic loop regions of the transmembrane domains initiate the transport cycle. In this review we summarize the current knowledge on receptor-transporter interplay provided by crystal structures as well as by biochemical and biophysical means. In particular, we focus on the maltose/maltodextrin transporter of enterobacteria and the transporters for positively charged amino acids from the thermophile Geobacillus stearothermophilus and Salmonella enterica serovar Typhimurium.

  9. Transport of monocarboxylic acids at the blood-brain barrier: Studies with monolayers of primary cultured bovine brain capillary endothelial cells

    SciTech Connect

    Terasaki, T.; Takakuwa, S.; Moritani, S.; Tsuji, A. )

    1991-09-01

    The kinetics and mechanism of the transport of monocarboxylic acids (MCAs) were studied by using primary cultured bovine brain capillary endothelial cells. Concentration-dependent uptake of acetic acid was observed, and the kinetic parameters were estimated as follows: the Michaelis constant, Kt, was 3.41 {plus minus} 1.87 mM, the maximum uptake rate, Jmax, was 144.7 {plus minus} 55.7 nmol/mg of protein/min and the nonsaturable first-order rate constant, Kd, was 6.66 {plus minus} 1.98 microliters/mg of protein/min. At medium pH below 7.0, the uptake rate of (3H)acetic acid increased markedly with decreasing medium pH, whereas pH-independent uptake was observed in the presence of 10 mM acetic acid. An energy requirement for (3H)acetic acid uptake was also demonstrated, because metabolic inhibitors (2,4-dinitrophenol and rotenone) reduced significantly the uptake rate (P less than .05). Carbonylcyanide-p-trifluoro-methoxyphenylhydrazone, a protonophore, inhibited significantly the uptake of (3H)acetic acid at medium pH of 5.0 and 6.0, whereas 4,4{prime}-diisothiocyanostilben-2,2{prime}-disulfonic acid did not. Several MCAs inhibited significantly the uptake rate of (3H)acetic acid, whereas di- and tricarboxylic acids did not. The uptake of (3H)acetic acid was competitively inhibited by salicylic acid, with an inhibition constant, Ki, of 3.60 mM, suggesting a common transport system between acetic acid and salicylic acid. Moreover, at the medium pH of 7.4, salicylic acid and valproic acid inhibited significantly the uptake of (3H)acetic acid, demonstrating that the transport of MCA drugs could also be ascribed to the MCA transport system at the physiologic pH.

  10. MODELING CONTAMINANT TRANSPORT THROUGH SUBSURFACE SYSTEMS

    EPA Science Inventory

    Modeling of contaminant transport through soil to groundwater to a receptor requires that consideration be given to the many processes which control the transport and fate of chemical constituents in the subsurface environment. These processes include volatilization, degradation,...

  11. Role of organic acids in promoting colloidal transport of mercury from mine tailings

    USGS Publications Warehouse

    Slowey, A.J.; Johnson, S.B.; Rytuba, J.J.; Brown, Gordon E.

    2005-01-01

    A number of factors affect the transport of dissolved and paniculate mercury (Hg) from inoperative Hg mines, including the presence of organic acids in the rooting zone of vegetated mine waste. We examined the role of the two most common organic acids in soils (oxalic and citric acid) on Hg transport from such waste by pumping a mixed organic acid solution (pH 5.7) at 1 mL/min through Hg mine tailings columns. For the two total organic acid concentrations investigated (20 ??M and 1 mM), particle-associated Hg was mobilized, with the onset of paniculate Hg transport occurring later for the lower organic acid concentration. Chemical analyses of column effluent indicate that 98 wt % of Hg mobilized from the column was paniculate. Hg speciation was determined using extended X-ray absorption fine structure spectroscopy and transmission electron microscopy, showing that HgS minerals are dominant in the mobilized particles. Hg adsorbed to colloids is another likely mode of transport due to the abundance of Fe-(oxyhydr)oxides, Fe-sulfides, alunite, and jarosite in the tailings to which Hg(II) adsorbs. Organic acids produced by plants are likely to enhance the transport of colloid-associated Hg from vegetated Hg mine tailings by dissolving cements to enable colloid release. ?? 2005 American Chemical Society.

  12. Role of organic acids in promoting colloidal transport of mercury from mine tailings.

    PubMed

    Slowey, Aaron J; Johnson, Stephen B; Rytuba, James J; Brown, Gordon E

    2005-10-15

    A number of factors affect the transport of dissolved and particulate mercury (Hg) from inoperative Hg mines, including the presence of organic acids in the rooting zone of vegetated mine waste. We examined the role of the two most common organic acids in soils (oxalic and citric acid) on Hg transport from such waste by pumping a mixed organic acid solution (pH 5.7) at 1 mL/min through Hg mine tailings columns. For the two total organic acid concentrations investigated (20 microM and 1 mM), particle-associated Hg was mobilized, with the onset of particulate Hg transport occurring later for the lower organic acid concentration. Chemical analyses of column effluent indicate that 98 wt % of Hg mobilized from the column was particulate. Hg speciation was determined using extended X-ray absorption fine structure spectroscopy and transmission electron microscopy, showing that HgS minerals are dominant in the mobilized particles. Hg adsorbed to colloids is another likely mode of transport due to the abundance of Fe-(oxyhydr)oxides, Fe-sulfides, alunite, and jarosite in the tailings to which Hg(II) adsorbs. Organic acids produced by plants are likely to enhance the transport of colloid-associated Hg from vegetated Hg mine tailings by dissolving cements to enable colloid release.

  13. Combustion experimentation aboard the space transportation system

    NASA Technical Reports Server (NTRS)

    Dewitt, R. L.

    1981-01-01

    A description is presented of the preliminary concept, specifications, and general requirements of a proposed Combustion Facility (CF) for the Spacelab payload of the Space Transportation System. The CF will permit an experimenter to use suitably contained liquid, gas, or solid fuels. He can specify and establish the composition and pressure level of the atmosphere in which the combustion will take place. It will be possible to characterize the experiment with common types of instrumentation as well as selected specialized equipment, to study the combustion process visually by direct observation and by motion picture coverage, and to obtain time histories of pertinent experimental parameters. During an experimental period, the CF will depend on Spacelab resources for power, heat rejection, and vacuum. Activating the CF and preparing it for the various experiments, performing the experiments, and shutting down the facility will be largely manual operations performed by flight personnel.

  14. Fuel cell system for transportation applications

    DOEpatents

    Kumar, R.; Ahmed, S.; Krumpelt, M.; Myles, K.M.

    1993-09-28

    A propulsion system is described for a vehicle having pairs of front and rear wheels and a fuel tank. An electrically driven motor having an output shaft operatively connected to at least one of said pair of wheels is connected to a fuel cell having a positive electrode and a negative electrode separated by an electrolyte for producing dc power to operate the motor. A partial oxidation reformer is connected both to the fuel tank and to the fuel cell and receives hydrogen-containing fuel from the fuel tank and uses water and air for partially oxidizing and reforming the fuel in the presence of an oxidizing catalyst and a reforming catalyst to produce a hydrogen-containing gas. The hydrogen-containing gas is sent from the partial oxidation reformer to the fuel cell negative electrode while air is transported to the fuel cell positive electrode to produce dc power for operating the electric motor. 3 figures.

  15. Fuel cell system for transportation applications

    DOEpatents

    Kumar, Romesh; Ahmed, Shabbir; Krumpelt, Michael; Myles, Kevin M.

    1993-01-01

    A propulsion system for a vehicle having pairs of front and rear wheels and a fuel tank. An electrically driven motor having an output shaft operatively connected to at least one of said pair of wheels is connected to a fuel cell having a positive electrode and a negative electrode separated by an electrolyte for producing dc power to operate the motor. A partial oxidation reformer is connected both to the fuel tank and to the fuel cell receives hydrogen-containing fuel from the fuel tank and water and air and for partially oxidizing and reforming the fuel with water and air in the presence of an oxidizing catalyst and a reforming catalyst to produce a hydrogen-containing gas. The hydrogen-containing gas is sent from the partial oxidation reformer to the fuel cell negative electrode while air is transported to the fuel cell positive electrode to produce dc power for operating the electric motor.

  16. Fireworthiness of transport aircraft interior systems

    NASA Technical Reports Server (NTRS)

    Parker, J. A.; Kourtides, D. A.

    1981-01-01

    The key materials question is addressed concerning the effect of interior systems on the survival of passengers and crew in the case of an uncontrolled transport aircraft fire. Technical opportunities are examined which are available through the modification of aircraft interior subsystem components, modifications that may reasonably be expected to provide improvements in aircraft fire safety. Subsystem components discussed are interior panels, seats, and windows. By virtue of their role in real fire situations and as indicated by the results of large scale simulation tests, these components appear to offer the most immediate and highest payoff possible by modifying interior materials of existing aircraft. These modifications have the potential of reducing the rate of fire growth, with a consequent reduction of heat, toxic gas, and smoke emission throughout the habitable interior of an aircraft, whatever the initial source of the fire.

  17. Space transportation system solid rocket booster thrust vector control system

    NASA Technical Reports Server (NTRS)

    Verble, A. J., Jr.; Mccool, A. A.; Potter, J. H.

    1979-01-01

    The Solid Rocket Booster, Thrust Vector Control (TVC) system was designed in accordance with the following requirements: self-contained power supply, fail-safe operation, 20 flight uses after exposure to seawater landings, optimized cost, and component interchangeability. Trade studies were performed which led to the selection of a recirculating hydraulic system powered by Auxiliary Power Units (APU) which drive the hydraulic actuators and gimbal the solid rocket motor nozzle. Other approaches for the system design were studied in arriving at the recirculating hydraulic system powered by an APU. These systems must withstand the imposed environment and be usable for a minimum of 20 Space Transportation System flights with a minimum of refurbishment. The TVC system has completed the major portion of qualification and verification tests and is prepared to be cleared for the first Shuttle flight (STS-1). Substantiation data will include analytical and test data.

  18. Space Transportation System solid rocket booster thrust vector control system

    NASA Technical Reports Server (NTRS)

    Verble, A. J., Jr.; Mccool, A. A.; Potter, J. H.

    1980-01-01

    The Solid Rocket Booster, Thrust Vector Control (TVC) system was designed in accordance with the following requirements: self-contained power supply, failsafe operation, 20 flight uses after exposure to seawater landings, optimized cost, and component interchangeability. Trade studies were performed which led to the selection of a recirculating hydraulic system powered by Auxiliary Power Units (APU) which drive the hydraulic actuators and gimbal the solid rocket motor nozzle. Other approaches for the system design were studied in arriving at the recirculating hydraulic system powered by an APU. These systems must withstand the imposed environment and be usable for a minimum of 20 Space Transportation System flights with a minimum of refurbishment. The TVC system completed the required qualification and verification tests and is certified for the intended application. Substantiation data include analytical and test data.

  19. In-stream sorption of fulvic acid in an acidic stream: A stream-scale transport experiment

    USGS Publications Warehouse

    McKnight, Diane M.; Hornberger, G.M.; Bencala, K.E.; Boyer, E.W.

    2002-01-01

    The variation of concentration and composition of dissolved organic carbon (DOC) in stream waters cannot be explained solely on the basis of soil processes in contributing subcatchments. To investigate in-stream processes that control DOC, we injected DOC-enriched water into a reach of the Snake River (Summit County, Colorado) that has abundant iron oxyhydroxides coating the streambed. The injected water was obtained from the Suwannee River (Georgia), which is highly enriched in fulvic acid. The fulvic acid from this water is the standard reference for aquatic fulvic acid for the International Humic Substances Society and has been well characterized. During the experimental injection, significant removal of sorbable fulvic acid occurred within the first 141 m of stream reach. We coinjected a conservative tracer (lithium chloride) and analyzed the results with the one-dimensional transport with inflow and storage (OTIS) stream solute transport model to quantify the physical transport mechanisms. The downstream transport of fulvic acid as indicated by absorbance was then simulated using OTIS with a first-order kinetic sorption rate constant applied to the sorbable fulvic acid. The "sorbable" fraction of injected fulvic acid was irreversibly sorbed by streambed sediments at rates (kinetic rate constants) of the order of 10-4-10-3 S-1. In the injected Suwannee River water, sorbable and nonsorbable fulvic acid had distinct chemical characteristics identified in 13C-NMR spectra. The 13C-NMR spectra indicate that during the experiment, the sorbable "signal" of greater aromaticity and carboxyl content decreased downstream; that is, these components were preferentially removed. This study illustrates that interactions between the water and the reactive surfaces will modify significantly the concentration and composition of DOC observed in streams with abundant chemically reactive surfaces on the streambed and in the hyporheic zone.

  20. The air transportation/energy system

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The changing pattern of transportation is discussed, and the energy intensiveness of various modes of transportation is also analyzed. Sociopsychological data affecting why people travel by air are presented, along with governmental regulation and air transportation economics. The aviation user tax structure is shown in tabular form.

  1. Maternal bile acid transporter deficiency promotes neonatal demise

    PubMed Central

    Zhang, Yuanyuan; Li, Fei; Wang, Yao; Pitre, Aaron; Fang, Zhong-ze; Frank, Matthew W.; Calabrese, Christopher; Krausz, Kristopher W.; Neale, Geoffrey; Frase, Sharon; Vogel, Peter; Rock, Charles O.; Gonzalez, Frank J.; Schuetz, John D.

    2015-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse neonatal survival and is estimated to impact between 0.4 and 5% of pregnancies worldwide. Here we show that maternal cholestasis (due to Abcb11 deficiency) produces neonatal death among all offspring within 24 h of birth due to atelectasis-producing pulmonary hypoxia, which recapitulates the neonatal respiratory distress of human ICP. Neonates of Abcb11-deficient mothers have elevated pulmonary bile acids and altered pulmonary surfactant structure. Maternal absence of Nr1i2 superimposed on Abcb11 deficiency strongly reduces maternal serum bile acid concentrations and increases neonatal survival. We identify pulmonary bile acids as a key factor in the disruption of the structure of pulmonary surfactant in neonates of ICP. These findings have important implications for neonatal respiratory failure, especially when maternal bile acids are elevated during pregnancy, and highlight potential pathways and targets amenable to therapeutic intervention to ameliorate this condition. PMID:26416771

  2. Maternal bile acid transporter deficiency promotes neonatal demise.

    PubMed

    Zhang, Yuanyuan; Li, Fei; Wang, Yao; Pitre, Aaron; Fang, Zhong-Ze; Frank, Matthew W; Calabrese, Christopher; Krausz, Kristopher W; Neale, Geoffrey; Frase, Sharon; Vogel, Peter; Rock, Charles O; Gonzalez, Frank J; Schuetz, John D

    2015-09-29

    Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse neonatal survival and is estimated to impact between 0.4 and 5% of pregnancies worldwide. Here we show that maternal cholestasis (due to Abcb11 deficiency) produces neonatal death among all offspring within 24 h of birth due to atelectasis-producing pulmonary hypoxia, which recapitulates the neonatal respiratory distress of human ICP. Neonates of Abcb11-deficient mothers have elevated pulmonary bile acids and altered pulmonary surfactant structure. Maternal absence of Nr1i2 superimposed on Abcb11 deficiency strongly reduces maternal serum bile acid concentrations and increases neonatal survival. We identify pulmonary bile acids as a key factor in the disruption of the structure of pulmonary surfactant in neonates of ICP. These findings have important implications for neonatal respiratory failure, especially when maternal bile acids are elevated during pregnancy, and highlight potential pathways and targets amenable to therapeutic intervention to ameliorate this condition.

  3. Plasma membrane H+ and K+ transporters are involved in the weak-acid preservative response of disparate food spoilage yeasts.

    PubMed

    Macpherson, Neil; Shabala, Lana; Rooney, Henrietta; Jarman, Marcus G; Davies, Julia M

    2005-06-01

    The food spoilage yeasts Zygosaccharomyces bailii and Saccharomyces cerevisiae have been proposed to resist weak-acid preservative stress by different means; Z. bailii by limiting influx of preservative combined with its catabolism, S. cerevisiae by active extrusion of the preservative weak-acid anion and H(+). Measurement of H(+) extrusion by exponential-phase Z. bailii cells suggest that, in common with S. cerevisiae, this yeast uses a plasma membrane H(+)-ATPase to expel H(+) when challenged by weak-acid preservative (benzoic acid). Simultaneous measurement of Z. bailii net H(+) and K(+) fluxes showed that net K(+) influx accompanies net H(+) efflux during acute benzoic acid stress. Such ionic coupling is known for S. cerevisiae in short-term preservative stress. Both yeasts significantly accumulated K(+) on long-term exposure to benzoic acid. Analysis of S. cerevisiae K(+) transporter mutants revealed that loss of the high affinity K(+) uptake system Trk1 confers sensitivity to growth in preservative. The results suggest that cation accumulation is an important factor in adaptation to weak-acid preservatives by spoilage yeasts and that Z. bailii and S. cerevisiae share hitherto unsuspected adaptive responses at the level of plasma membrane ion transport.

  4. The SLC36 family of proton-coupled amino acid transporters and their potential role in drug transport

    PubMed Central

    Thwaites, David T; Anderson, Catriona MH

    2011-01-01

    Members of the solute carrier (SLC) 36 family are involved in transmembrane movement of amino acids and derivatives. SLC36 consists of four members. SLC36A1 and SLC36A2 both function as H+-coupled amino acid symporters. SLC36A1 is expressed at the luminal surface of the small intestine but is also commonly found in lysosomes in many cell types (including neurones), suggesting that it is a multipurpose carrier with distinct roles in different cells including absorption in the small intestine and as an efflux pathway following intralysosomal protein breakdown. SLC36A1 has a relatively low affinity (Km 1–10 mM) for its substrates, which include zwitterionic amino and imino acids, heterocyclic amino acids and amino acid-based drugs and derivatives used experimentally and/or clinically to treat epilepsy, schizophrenia, bacterial infections, hyperglycaemia and cancer. SLC36A2 is expressed at the apical surface of the human renal proximal tubule where it functions in the reabsorption of glycine, proline and hydroxyproline. SLC36A2 also transports amino acid derivatives but has a narrower substrate selectivity and higher affinity (Km 0.1–0.7 mM) than SLC36A1. Mutations in SLC36A2 lead to hyperglycinuria and iminoglycinuria. SLC36A3 is expressed only in testes and is an orphan transporter with no known function. SLC36A4 is widely distributed at the mRNA level and is a high-affinity (Km 2–3 µM) transporter for proline and tryptophan. We have much to learn about this family of transporters, but from current knowledge, it seems likely that their function will influence the pharmacokinetic profiles of amino acid-based drugs by mediating transport in both the small intestine and kidney. LINKED ARTICLES This article is part of a themed section on Transporters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2011.164.issue-7 PMID:21501141

  5. Regulation of amino acid transporter trafficking by mTORC1 in primary human trophoblast cells is mediated by the ubiquitin ligase Nedd4-2.

    PubMed

    Rosario, Fredrick J; Dimasuay, Kris Genelyn; Kanai, Yoshikatsu; Powell, Theresa L; Jansson, Thomas

    2016-04-01

    Changes in placental amino acid transfer directly contribute to altered fetal growth, which increases the risk for perinatal complications and predisposes for the development of obesity, diabetes and cardiovascular disease later in life. Placental amino acid transfer is critically dependent on the expression of specific transporters in the plasma membrane of the trophoblast, the transporting epithelium of the human placenta. However, the molecular mechanisms regulating this process are largely unknown. Nedd4-2 is an ubiquitin ligase that catalyses the ubiquitination of proteins, resulting in proteasomal degradation. We hypothesized that inhibition of mechanistic target of rapamycin complex 1 (mTORC1) decreases amino acid uptake in primary human trophoblast (PHT) cells by activation of Nedd4-2, which increases transporter ubiquitination resulting in decreased transporter expression in the plasma membrane. mTORC 1 inhibition increased the expression of Nedd4-2, promoted ubiquitination and decreased the plasma membrane expression of SNAT2 (an isoform of the System A amino acid transporter) and LAT1 (a System L amino acid transporter isoform), resulting in decreased cellular amino acid uptake. Nedd4-2 silencing markedly increased the trafficking of SNAT2 and LAT1 to the plasma membrane, which stimulated cellular amino acid uptake. mTORC1 inhibition by silencing of raptor failed to decrease amino acid transport following Nedd4-2 silencing. In conclusion, we have identified a novel link between mTORC1 signalling and ubiquitination, a common posttranslational modification. Because placental mTORC1 is inhibited in fetal growth restriction and activated in fetal overgrowth, we propose that regulation of placental amino acid transporter ubiquitination by mTORC1 and Nedd4-2 constitutes a molecular mechanisms underlying abnormal fetal growth.

  6. Transportation impact analysis for the shipment of low specific activity nitric acid. Revisison 1

    SciTech Connect

    Green, J.R.

    1995-05-16

    This is in support of the Plutonium-Uranium Extraction (PUREX) Facility Low Specific Activity (LSA) Nitric Acid Shipment Environmental Assessment. It analyzes potential toxicological and radiological risks associated with transportation of PUREX Facility LSA Nitric Acid from the Hanford Site to Portsmouth VA, Baltimore MD, and Port Elizabeth NJ.

  7. Transport of Corilagin, Gallic Acid, and Ellagic Acid from Fructus Phyllanthi Tannin Fraction in Caco-2 Cell Monolayers

    PubMed Central

    Zhao, Hai-juan; Liang, Wen-Yi; Chen, Wen-Jing; Han, Shu-Xian; Qi, Qi; Cui, Ya-Ping; Li, Shi; Yang, Guang-Hui; Shao, Yan-Yan; Zhu, Dan

    2016-01-01

    Objective. To investigate the absorption property of the representative hydrolyzable tannin, namely corilagin, and its hydrolysates gallic acid (GA) and ellagic acid (EA) from the Fructus Phyllanthi tannin fraction (PTF) in vitro. Methods. Caco-2 cells monolayer model was established. Influences of PTF on Caco-2 cells viability were detected with MTT assay. The transport across monolayers was examined for different time points, concentrations, and secretory directions. The inhibitors of P-glycoprotein (P-gp), multidrug resistance proteins (MRPs), organic anion transporting polypeptide (OATP) and sodium/glucose cotransporter 1 (SGLT1), and tight junction modulators were used to study the transport mechanism. LC-MS method was employed to quantify the absorption concentration. Results. The apparent permeability coefficient (Papp) values of the three compounds were below 1.0 × 10−6 cm/s. The absorption of corilagin and GA were much lower than their efflux, and the uptake of both compounds was increased in the presence of inhibitors of P-gp and MRPs. The absorption of EA was decreased in the company of OATP and SGLT1 inhibitors. Moreover, the transport of corilagin, GA, and EA was enhanced by tight junction modulators. Conclusion. These observations indicated that the three compounds in PTF were transported via passive diffusion combined with protein mediated transport. P-gp and MRPs might get involved in the transport of corilagin and GA. The absorption of EA could be attributed to OATP and SGLT1 protein. PMID:27738446

  8. Argonne simulation framework for intelligent transportation systems

    SciTech Connect

    Ewing, T.; Doss, E.; Hanebutte, U.; Canfield, T.; Brown-VanHoozer, A.; Tentner, A.

    1996-04-01

    A simulation framework has been developed which defines a high-level architecture for a large-scale, comprehensive, scalable simulation of an Intelligent Transportation System (ITS). The simulator is designed to run on parallel computers and distributed (networked) computer systems; however, a version for a stand alone workstation is also available. The ITS simulator includes an Expert Driver Model (EDM) of instrumented ``smart`` vehicles with in-vehicle navigation units. The EDM is capable of performing optimal route planning and communicating with Traffic Management Centers (TMC). A dynamic road map data base is sued for optimum route planning, where the data is updated periodically to reflect any changes in road or weather conditions. The TMC has probe vehicle tracking capabilities (display position and attributes of instrumented vehicles), and can provide 2-way interaction with traffic to provide advisories and link times. Both the in-vehicle navigation module and the TMC feature detailed graphical user interfaces that includes human-factors studies to support safety and operational research. Realistic modeling of variations of the posted driving speed are based on human factor studies that take into consideration weather, road conditions, driver`s personality and behavior and vehicle type. The simulator has been developed on a distributed system of networked UNIX computers, but is designed to run on ANL`s IBM SP-X parallel computer system for large scale problems. A novel feature of the developed simulator is that vehicles will be represented by autonomous computer processes, each with a behavior model which performs independent route selection and reacts to external traffic events much like real vehicles. Vehicle processes interact with each other and with ITS components by exchanging messages. With this approach, one will be able to take advantage of emerging massively parallel processor (MPP) systems.

  9. Myosin 1b Regulates Amino Acid Transport by Associating Transporters with the Apical Plasma Membrane of Kidney Cells

    PubMed Central

    Komaba, Shigeru; Coluccio, Lynne M.

    2015-01-01

    Amino acid transporters (AATers) in the brush border of the apical plasma membrane (APM) of renal proximal tubule (PT) cells mediate amino acid transport (AAT). We found that the membrane-associated class I myosin myosin 1b (Myo1b) localized at the apical brush border membrane of PTs. In opossum kidney (OK) 3B/2 epithelial cells, which are derived from PTs, expressed rat Myo1b-GFP colocalized in patched microvilli with expressed mouse V5-tagged SIT1 (SIT1-V5), which mediates neutral amino acid transport in OK cells. Lentivirus-mediated delivery of opossum Myo1b-specific shRNA resulted in knockdown (kd) of Myo1b expression, less SIT1-V5 at the APM as determined by localization studies, and a decrease in neutral AAT as determined by radioactive uptake assays. Myo1b kd had no effect on Pi transport or noticeable change in microvilli structure as determined by rhodamine phalloidin staining. The studies are the first to define a physiological role for Myo1b, that of regulating renal AAT by modulating the association of AATers with the APM. PMID:26361046

  10. Myosin 1b Regulates Amino Acid Transport by Associating Transporters with the Apical Plasma Membrane of Kidney Cells.

    PubMed

    Komaba, Shigeru; Coluccio, Lynne M

    2015-01-01

    Amino acid transporters (AATers) in the brush border of the apical plasma membrane (APM) of renal proximal tubule (PT) cells mediate amino acid transport (AAT). We found that the membrane-associated class I myosin myosin 1b (Myo1b) localized at the apical brush border membrane of PTs. In opossum kidney (OK) 3B/2 epithelial cells, which are derived from PTs, expressed rat Myo1b-GFP colocalized in patched microvilli with expressed mouse V5-tagged SIT1 (SIT1-V5), which mediates neutral amino acid transport in OK cells. Lentivirus-mediated delivery of opossum Myo1b-specific shRNA resulted in knockdown (kd) of Myo1b expression, less SIT1-V5 at the APM as determined by localization studies, and a decrease in neutral AAT as determined by radioactive uptake assays. Myo1b kd had no effect on Pi transport or noticeable change in microvilli structure as determined by rhodamine phalloidin staining. The studies are the first to define a physiological role for Myo1b, that of regulating renal AAT by modulating the association of AATers with the APM. PMID:26361046

  11. Acid sensing by the Drosophila olfactory system.

    PubMed

    Ai, Minrong; Min, Soohong; Grosjean, Yael; Leblanc, Charlotte; Bell, Rati; Benton, Richard; Suh, Greg S B

    2010-12-01

    The odour of acids has a distinct quality that is perceived as sharp, pungent and often irritating. How acidity is sensed and translated into an appropriate behavioural response is poorly understood. Here we describe a functionally segregated population of olfactory sensory neurons in the fruitfly, Drosophila melanogaster, that are highly selective for acidity. These olfactory sensory neurons express IR64a, a member of the recently identified ionotropic receptor (IR) family of putative olfactory receptors. In vivo calcium imaging showed that IR64a+ neurons projecting to the DC4 glomerulus in the antennal lobe are specifically activated by acids. Flies in which the function of IR64a+ neurons or the IR64a gene is disrupted had defects in acid-evoked physiological and behavioural responses, but their responses to non-acidic odorants remained unaffected. Furthermore, artificial stimulation of IR64a+ neurons elicited avoidance responses. Taken together, these results identify cellular and molecular substrates for acid detection in the Drosophila olfactory system and support a labelled-line mode of acidity coding at the periphery. PMID:21085119

  12. Sulfuric acid thermoelectrochemical system and method

    DOEpatents

    Ludwig, Frank A.

    1989-01-01

    A thermoelectrochemical system in which an electrical current is generated between a cathode immersed in a concentrated sulfuric acid solution and an anode immersed in an aqueous buffer solution of sodium bisulfate and sodium sulfate. Reactants consumed at the electrodes during the electrochemical reaction are thermochemically regenerated and recycled to the electrodes to provide continuous operation of the system.

  13. Micro-electro-mechanical systems phosphoric acid fuel cell

    DOEpatents

    Sopchak, David A.; Morse, Jeffrey D.; Upadhye, Ravindra S.; Kotovsky, Jack; Graff, Robert T.

    2010-08-17

    A phosphoric acid fuel cell system comprising a porous electrolyte support, a phosphoric acid electrolyte in the porous electrolyte support, a cathode electrode contacting the phosphoric acid electrolyte, and an anode electrode contacting the phosphoric acid electrolyte.

  14. Micro-electro-mechanical systems phosphoric acid fuel cell

    DOEpatents

    Sopchak, David A.; Morse, Jeffrey D.; Upadhye, Ravindra S.; Kotovsky, Jack; Graff, Robert T.

    2010-12-21

    A phosphoric acid fuel cell system comprising a porous electrolyte support, a phosphoric acid electrolyte in the porous electrolyte support, a cathode electrode contacting the phosphoric acid electrolyte, and an anode electrode contacting the phosphoric acid electrolyte.

  15. Role for Ion Transport in Porcine Vocal Fold Epithelial Defense to Acid Challenge

    PubMed Central

    Erickson-Levendoski, Elizabeth; Sivasankar, M. Preeti

    2012-01-01

    Objective The vocal fold epithelium is routinely exposed to gastric contents, including acid and pepsin, during laryngopharyngeal reflux events. The epithelium may possess intrinsic defenses to reflux. The first objective of the current study was to examine whether vocal fold epithelial ion transport is one potential mechanism of defense to gastric contents. The second objective was to determine whether ion transport in response to gastric contents is associated with the secretion of bicarbonate. Study Design Prospective design in excised porcine larynges. Setting Laboratory. Subjects and Methods Porcine vocal folds (N = 56) were exposed on the luminal surface to acid, pepsin, or sham challenges. Ion transport at baseline and following challenge exposure was measured using electrophysiological techniques. To examine specific ion transport mechanisms, vocal folds were pretreated with either a sodium channel blocker or bicarbonate channel blocker. Results Within 60 seconds of acid but not pepsin exposure, there was a significant increase in ion transport. This rapid increase in ion transport was transient and related to bicarbonate secretion. Conclusion The current data suggest that porcine vocal folds immediately increase bicarbonate secretion following exposure to acid. Bicarbonate secretion may act to neutralize acid. These findings contribute to the identification of the mechanisms underlying vocal fold defense to reflux and offer implications for the development of treatments for reflux-induced vocal fold injury. PMID:22086905

  16. Characterization and astrocytic modulation of system L transporters in brain microvasculature endothelial cells.

    PubMed

    Omidi, Yadollah; Barar, Jaleh; Ahmadian, Somaieh; Heidari, Hamid Reza; Gumbleton, Mark

    2008-04-01

    Brain trafficking of amino acids is mainly mediated by amino acids transport machineries of the blood-brain barrier (BBB), where astrocytes play a key maintenance role. However, little is known about astrocytes impacts on such transport systems, in particular system L that consists of large and small neutral amino acids (NAAs) transporters, that is, LAT1/4F2hc and LAT2/4F2hc, respectively. In the current investigation, functionality and expression of system L were studied in the immortalized mouse brain microvascular endothelial b.End3 cells cocultured with astrocytes or treated with astrocyte-conditioned media (ACM). LAT2/4F2hc mediated luminal uptake of L-phenylalanine and L-leucine resulted in significantly decreased affinity of system L in b.End3 cells treated with ACM, while LAT2/4F2hc mediated luminal uptake of L-alanine remained unchanged. Gene expression analysis revealed marked upregulation of LAT1 and 4F2hc, but downregulation of LAT2 in b.End3 cells cultured with ACM. The basal to apical transport of L-phenylalanine and L-alanine appeared to be significantly greater than that of the apical to basal direction in b.End3 cells indicating an efflux functionality of system L. No marked influence was observed for transport of L-phenylalanine in b.End3 cells cocultured with astrocytes, while a slight decrease was seen for L-alanine in the basal to apical direction. Based on our findings, we propose that system L functions as influx and/or efflux transport machinery displaying a greater propensity for the outward transport of large and small NAAs. Astrocytes appeared to modulate the transcriptic expression and uptake functionalities of system L, but not the transport activities. PMID:18210381

  17. OST alpha-OST beta: a key membrane transporter of bile acids and conjugated steroids.

    PubMed

    Ballatori, Nazzareno; Li, Na; Fang, Fang; Boyer, James L; Christian, Whitney V; Hammond, Christine L

    2009-01-01

    The organic solute and steroid transporter, Ost alpha-Ost beta, is an unusual heteromeric carrier that appears to play a central role in the transport of bile acids, conjugated steroids, and structurally-related molecules across the basolateral membrane of many epithelial cells. The transporter's substrate specificity, transport mechanism, tissue distribution, subcellular localization, transcriptional regulation, as well as the phenotype of the recently characterized Ost alpha-deficient mice all strongly support this model. In particular, the Ost alpha-deficient mice display a marked defect in intestinal bile acid and conjugated steroid absorption; a decrease in bile acid pool size and serum bile acid levels; altered intestinal, hepatic and renal disposition of known substrates of the transporter; and altered serum triglyceride, cholesterol, and glucose levels. Collectively, the data indicate that Ost alpha-Ost beta is essential for bile acid and sterol disposition, and suggest that the carrier may be involved in human conditions related to imbalances in bile acid or lipid homeostasis.

  18. Systematic Development of Intelligent Systems for Public Road Transport.

    PubMed

    García, Carmelo R; Quesada-Arencibia, Alexis; Cristóbal, Teresa; Padrón, Gabino; Alayón, Francisco

    2016-01-01

    This paper presents an architecture model for the development of intelligent systems for public passenger transport by road. The main objective of our proposal is to provide a framework for the systematic development and deployment of telematics systems to improve various aspects of this type of transport, such as efficiency, accessibility and safety. The architecture model presented herein is based on international standards on intelligent transport system architectures, ubiquitous computing and service-oriented architecture for distributed systems. To illustrate the utility of the model, we also present a use case of a monitoring system for stops on a public passenger road transport network. PMID:27438836

  19. Systematic Development of Intelligent Systems for Public Road Transport

    PubMed Central

    García, Carmelo R.; Quesada-Arencibia, Alexis; Cristóbal, Teresa; Padrón, Gabino; Alayón, Francisco

    2016-01-01

    This paper presents an architecture model for the development of intelligent systems for public passenger transport by road. The main objective of our proposal is to provide a framework for the systematic development and deployment of telematics systems to improve various aspects of this type of transport, such as efficiency, accessibility and safety. The architecture model presented herein is based on international standards on intelligent transport system architectures, ubiquitous computing and service-oriented architecture for distributed systems. To illustrate the utility of the model, we also present a use case of a monitoring system for stops on a public passenger road transport network. PMID:27438836

  20. Surfactant control of gas transport and reactions at the surface of sulfuric acid.

    PubMed

    Park, Seong-Chan; Burden, Daniel K; Nathanson, Gilbert M

    2009-02-17

    Aerosol particles in the atmosphere are tiny chemical reactors that catalyze numerous reactions, including the conversion of benign gases into ozone-destroying ones. In the lower stratosphere, these particles are often supercooled mixtures of water and sulfuric acid. The different species present at the surface of these droplets (H(2)O, H(3)O(+), HSO(4)(-), H(2)SO(4), and SO(4)(2-)) stand at the "gas-liquid frontier"; as the first to be struck by impinging molecules, these species provide the initial environment for solvation and reaction. Furthermore, aerosol particles may contain a wide range of organic molecules, some of which migrate to the surface and coat the droplet. How do ambient gases dissolve in the droplet if it is coated with an organic layer? At one extreme, monolayer films of insoluble, long-chain alcohols can dramatically reduce gas transport, packing so tightly at the surface of water that they impede water evaporation by factors of 10,000 or more. Shorter chain surfactants are expected to pack less tightly, but we wondered whether these incomplete monolayers also block gas transport and whether this system could serve as a model for understanding the surfaces of atmospheric aerosol particles. To address these questions, our research focuses on small, soluble surfactants such as butanol and hexanol dissolved in supercooled sulfuric acid. These amphiphilic molecules spontaneously segregate to the surface and coat the acid but only to a degree. Gas-liquid scattering experiments reveal that these porous films behave in surprisingly diverse ways: they can impose a barrier (to N(2)O(5) hydrolysis), be "invisible" (to water evaporation), or even enhance gas uptake (of HCl). The transition from obstacle to catalyst can be traced to specific interactions between the surfactant and each gas. For example, the hydrolysis of N(2)O(5) may be impeded because of its large size and because alcohol molecules that straddle the interface limit contact between N(2)O(5

  1. Surfactant control of gas transport and reactions at the surface of sulfuric acid.

    PubMed

    Park, Seong-Chan; Burden, Daniel K; Nathanson, Gilbert M

    2009-02-17

    Aerosol particles in the atmosphere are tiny chemical reactors that catalyze numerous reactions, including the conversion of benign gases into ozone-destroying ones. In the lower stratosphere, these particles are often supercooled mixtures of water and sulfuric acid. The different species present at the surface of these droplets (H(2)O, H(3)O(+), HSO(4)(-), H(2)SO(4), and SO(4)(2-)) stand at the "gas-liquid frontier"; as the first to be struck by impinging molecules, these species provide the initial environment for solvation and reaction. Furthermore, aerosol particles may contain a wide range of organic molecules, some of which migrate to the surface and coat the droplet. How do ambient gases dissolve in the droplet if it is coated with an organic layer? At one extreme, monolayer films of insoluble, long-chain alcohols can dramatically reduce gas transport, packing so tightly at the surface of water that they impede water evaporation by factors of 10,000 or more. Shorter chain surfactants are expected to pack less tightly, but we wondered whether these incomplete monolayers also block gas transport and whether this system could serve as a model for understanding the surfaces of atmospheric aerosol particles. To address these questions, our research focuses on small, soluble surfactants such as butanol and hexanol dissolved in supercooled sulfuric acid. These amphiphilic molecules spontaneously segregate to the surface and coat the acid but only to a degree. Gas-liquid scattering experiments reveal that these porous films behave in surprisingly diverse ways: they can impose a barrier (to N(2)O(5) hydrolysis), be "invisible" (to water evaporation), or even enhance gas uptake (of HCl). The transition from obstacle to catalyst can be traced to specific interactions between the surfactant and each gas. For example, the hydrolysis of N(2)O(5) may be impeded because of its large size and because alcohol molecules that straddle the interface limit contact between N(2)O(5

  2. Intelligent transportation infrastructure deployment analysis system

    SciTech Connect

    Rathi, A.K.; Harding, J.A.

    1997-02-01

    Much of the work on Intelligent Transportation Systems (ITS) to date has emphasized technologies, standards/protocols, architecture, user services, core infrastructure requirements, and various other technical and institutional issues. ITS implementations in the United States and elsewhere in the world have demonstrated benefits in the areas of safety, productivity, efficiency, and environmental impact. However, quantitative benefits and satisfactory cost estimates are not available or cannot be derived for many components of the ITS, whether deployed individually or in some integrated fashion. The limitations of existing analysis and evaluation capabilities coupled with the lack of strong empirical evidence presents a major knowledge and data gap for infrastructure investment decisions involving ITS alternatives. This paper describes the over-arching issues and requirements associated with the analysis capabilities required for a systematic, faithful, and rigorous evaluation of the impacts of deploying ITS in a metropolitan area. It then describes the conceptual framework of a modeling system that will provide a preliminary analysis capability to support ITS deployment analysis and evaluation.

  3. Advanced space transportation systems, BARGOUZIN booster

    NASA Astrophysics Data System (ADS)

    Prampolini, Marco; Louaas, Eric; Prel, Yves; Kostromin, Sergey; Panichkin, Nickolay; Sumin, Yuriy; Osin, Mikhail; Iranzo-Greus, David; Rigault, Michel; Beaurain, André; Couteau, Jean-Noël

    2008-07-01

    In the framework of Advanced Space Transportation Systems Studies sponsored by CNES in 2006, a study called "BARGOUZIN" was performed by a joint team led by ASTRIUM ST and TSNIIMASH. Beyond these leaders, the team comprised MOLNIYA, DASSAULT AVIATION and SNECMA as subcontractors. The "BARGOUZIN" concept is a liquid fuelled fly-back booster (LFBB), mounted on the ARIANE 5 central core stage in place of the current solid rocket booster. The main originality of the concept lies in the fact that the "BARGOUZIN" features a cluster of VULCAIN II engines, similar to the one mounted on the central core stage of ARIANE 5. An astute permutation strategy, between the booster engines and central core engine is expected to lead to significant cost reductions. The following aspects were addressed during the preliminary system study: engine number per booster trade-off/abort scenario analysis, aerodynamic consolidation, engine reliability, ascent controllability, ground interfaces separation sequence analysis, programmatics. These topics will be briefly presented and synthesized in this paper, giving an overview of the credibility of the concept.

  4. NANONIS TRAMEA - A Quantum Transport Measurement System

    NASA Astrophysics Data System (ADS)

    Kampen, Thorsten; Thissen, Andreas; Schaff, Oliver; Pioda, Alessandro

    Nanonis Tramea is a quantum leap with respect to increased speed for transport measurements taking research onto a new level. Measurements which took several hours in the past can now be done in minutes without compromising signal quality. Tramea uses its fast, high-resolution, high-precision and ultra-low-noise outputs and inputs to generate and acquire up to 20000 data points per second on 24 channels in parallel. This is not only up to 1000 x faster than typical measurement systems but it is also time deterministic with highest precision. Here, the time separation between points is constant so that artefacts caused by unequal point spacings in non-deterministic measurement systems are avoided. The emphasis here is the real-time relation. Tramea comes with a built-in interface which allows for control of the instruments' basic functions from any programming environment. For users requiring more functionality and higher speeds a full-featured LabVIEW-based programming interface or scripting module are available as add-on modules. Due to the modularity and flexibility of the hardware and software architecture of Tramea upgrades with standardized add-on modules are possible. Non-standard requests can still be handled by the various programming options.

  5. National Space Transportation Systems Program mission report

    NASA Technical Reports Server (NTRS)

    Collins, M. A., Jr.; Aldrich, A. D.; Lunney, G. S.

    1984-01-01

    The 515-41B National Space Transportation Systems Program Mission Report contains a summary of the major activities and accomplishments of the sixth operational Shuttle flight and fourth flight of the OV-099 vehicle, Challenger. Since this flight was the first to land at Kennedy Space Center, the vehicle was towed directly to the OPF (Orbiter Processing Facility) where preparations for flight STS-41C, scheduled for early April 1984, began immediately. The significant problems that occurred during STS-41B are summarized and a problem tracking list that is a complete list of all problems that occurred during the flight is given. None of the problems will affect the STS 41C flight. The major objectives of flight STS-41B were to successfully deploy the Westar satellite and the Indonesian Communications Satellite-B2 (PALAPA-B2); to evaluate the MMU (Manned Maneuvering Unit) support for EVA (Extravehicular Activities); to exercise the MFR (Manipulator Foot Restraint); to demonstrate a closed loop rendezvous; and to operate the M.R (Monodisperse Latex Reactor), the ACES (Acoustic Containerless Experiment System) and the IEF (Isoelectric Focusing) in cabin experiments; and to obtain photographs with the Cinema 360 Cameras.

  6. Modeling of facilitated transport of phenylalanine by emulsion liquid membranes with di(2-ethylhexyl)phosphoric acid as a carrier

    SciTech Connect

    Liu, X.; Liu, D.

    1998-12-01

    A mathematical model is developed in this paper to simulate the facilitated transport of phenylalanine (Phe) in emulsion liquid membrane (ELM) systems with di(2-ethylhexyl)phosphoric acid as a carrier. The model takes into account the mass transfer in both the external aqueous phase and the organic membrane phase interfacial reaction as well as membrane breakage during agitation. The model is tested by comparing theoretical predications with experimental results using Phe extraction by ELM processes. It is found that the model is valid for simulating the facilitated transport of Phe with ELM under various experimental conditions.

  7. A new prenylated flavone from Artocarpus champeden inhibits the K(+)-dependent amino acid transport in Bombyx mori midgut.

    PubMed

    Parenti, P; Pizzigoni, A; Hanozet, G; Hakim, E H; Makmur, L; Achmad, S A; Giordana, B

    1998-03-17

    The effect of some flavonoids on the K(+)-dependent and K(+)-independent leucine uptake into brush border membrane vesicles from Bombyx mori larval midgut was investigated. Among the compounds tested, cyclochampedol, recently purified from Artocarpus champeden, was able to inhibit in micromolar range the leucine transport. The inhibition occurred both in the absence and in the presence of potassium and was not affected by leucine concentration. The apparent Ki was 0.25 mM. Cyclochampedol represents the first non-competitive inhibitor of an amino acid transport system in Lepidoptera. The relevance of this result is discussed.

  8. 21 CFR 862.1290 - Fatty acids test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fatty acids test system. 862.1290 Section 862.1290....1290 Fatty acids test system. (a) Identification. A fatty acids test system is a device intended to measure fatty acids in plasma and serum. Measurements of fatty acids are used in the diagnosis...

  9. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Folic acid test system. 862.1295 Section 862.1295....1295 Folic acid test system. (a) Identification. A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis...

  10. Greater Transport Efficiencies of the Membrane Fatty Acid Transporters FAT/CD36 and FATP4 Compared with FABPpm and FATP1 and Differential Effects on Fatty Acid Esterification and Oxidation in Rat Skeletal Muscle*

    PubMed Central

    Nickerson, James G.; Alkhateeb, Hakam; Benton, Carley R.; Lally, James; Nickerson, Jennifer; Han, Xiao-Xia; Wilson, Meredith H.; Jain, Swati S.; Snook, Laelie A.; Glatz, Jan F. C.; Chabowski, Adrian; Luiken, Joost J. F. P.; Bonen, Arend

    2009-01-01

    In selected mammalian tissues, long chain fatty acid transporters (FABPpm, FAT/CD36, FATP1, and FATP4) are co-expressed. There is controversy as to whether they all function as membrane-bound transporters and whether they channel fatty acids to oxidation and/or esterification. Among skeletal muscles, the protein expression of FABPpm, FAT/CD36, and FATP4, but not FATP1, correlated highly with the capacities for oxidative metabolism (r ≥ 0.94), fatty acid oxidation (r ≥ 0.88), and triacylglycerol esterification (r ≥ 0.87). We overexpressed independently FABPpm, FAT/CD36, FATP1, and FATP4, within a normal physiologic range, in rat skeletal muscle, to determine the effects on fatty acid transport and metabolism. Independent overexpression of each fatty acid transporter occurred without altering either the expression or plasmalemmal content of other fatty acid transporters. All transporters increased fatty acid transport, but FAT/CD36 and FATP4 were 2.3- and 1.7-fold more effective than FABPpm and FATP1, respectively. Fatty acid transporters failed to alter the rates of fatty acid esterification into triacylglycerols. In contrast, all transporters increased the rates of long chain fatty acid oxidation, but the effects of FABPpm and FAT/CD36 were 3-fold greater than for FATP1 and FATP4. Thus, fatty acid transporters exhibit different capacities for fatty acid transport and metabolism. In vivo, FAT/CD36 and FATP4 are the most effective fatty acid transporters, whereas FABPpm and FAT/CD36 are key for stimulating fatty acid oxidation. PMID:19380575

  11. TransportDB: a relational database of cellular membrane transport systems.

    PubMed

    Ren, Qinghu; Kang, Katherine H; Paulsen, Ian T

    2004-01-01

    TransportDB (http://www.membranetransport.org) is a relational database designed for describing the predicted cellular membrane transport proteins in organisms whose complete genome sequences are available. For each organism, the complete set of membrane transport systems was identified and classified into different types and families according to putative membrane topology, protein family, bioenergetics and substrate specificities. Web pages were created to provide user-friendly interfaces to easily access, query and download the data. Additional features, such as a BLAST search tool against known transporter protein sequences, comparison of transport systems from different organisms and phylogenetic trees of individual transporter families are also provided. TransportDB will be regularly updated with data obtained from newly sequenced genomes.

  12. Up-regulation of gamma-aminobutyric acid transporter I mediates ethanol sensitivity in mice.

    PubMed

    Hu, J-H; Ma, Y-H; Yang, N; Mei, Z-T; Zhang, M-H; Fei, J; Guo, L-H

    2004-01-01

    Ethanol is among the most widely abused drugs in the world. Chronic ethanol consumption leads to ethanol tolerance and addiction, and impairs learning and memory. Na+/Cl- dependent GABA transporters play an important role in controlling the concentration of GABA in the synaptic cleft, and thus they control the intensity and duration of synaptic transmission of GABA. It has been suggested that GABAergic system is involved in ethanol consumption, tolerance and addiction, because chronic ethanol consumption alters the expression of GABAA receptors and drugs on GABA receptors affect ethanol actions. The results of the present study reveal that that activity of GABA transporters in mouse brain after 15-min acute ethanol injection or after chronic ethanol consumption is increased. Moreover, mice pre-injected with a competitive or a noncompetitive antagonist of gamma-aminobutyric acid transporter subtype 1 (GAT1) showed high sensitivity to the sedative/hypnotic effects of ethanol. In contrast, transgenic mice overexpressing GAT1 displayed low sensitivity to ethanol, as shown by the righting reflex test. Mice overexpressing GAT1 survived a lethal dose of ethanol (9 g/kg, i.p.) longer, maintained locomotor activity longer after a sub-lethal dose (1.75 g/kg, i.p.) and exhibited a higher median lethal dose than wild-type littermates. These results suggest that GAT1 plays an important role in sensitivity to ethanol, and might be a therapeutic target for alcoholism prevention and treatment. Acute and chronic ethanol administration resulted in the increase of GABA transporter function. Use of GAT1 selective inhibitors and GAT1 overexpressing mice thus demonstrate that GAT1 should be an important protein mediating sensitivity to ethanol in mice.

  13. Plasmalemmal and Vesicular γ-Aminobutyric Acid Transporter Expression in the Developing Mouse Retina

    PubMed Central

    GUO, CHENYING; STELLA, SALVATORE L.; HIRANO, ARLENE A.; BRECHA, NICHOLAS C.

    2009-01-01

    Plasmalemmal and vesicular γ-aminobutyric acid (GABA) transporters influence neurotransmission by regulating high-affinity GABA uptake and GABA release into the synaptic cleft and extracellular space. Postnatal expression of the plasmalemmal GABA transporter-1 (GAT-1), GAT-3, and the vesicular GABA/glycine transporter (VGAT) were evaluated in the developing mouse retina by using immunohistochemistry with affinity-purified antibodies. Weak transporter immunoreactivity was observed in the inner retina at postnatal day 0 (P0). GAT-1 immunostaining at P0 and at older ages was in amacrine and displaced amacrine cells in the inner nuclear layer (INL) and ganglion cell layer (GCL), respectively, and in their processes in the inner plexiform layer (IPL). At P10, weak GAT-1 immunostaining was in Müller cell processes. GAT-3 immunostaining at P0 and older ages was in amacrine cells and their processes, as well as in Müller cells and their processes that extended radially across the retina. At P10, Müller cell somata were observed in the middle of the INL. VGAT immunostaining was present at P0 and older ages in amacrine cells in the INL as well as processes in the IPL. At P5, weak VGAT immunostaining was also observed in horizontal cell somata and processes. By P15, the GAT and VGAT immunostaining patterns appear similar to the adult immunostaining patterns; they reached adult levels by about P20. These findings demonstrate that GABA uptake and release are initially established in the inner retina during the first postnatal week and that these systems subsequently mature in the outer retina during the second postnatal week. PMID:18975268

  14. Road transportable analytical laboratory (RTAL) system

    SciTech Connect

    Finger, S.M.

    1996-12-31

    Remediation of DOE contaminated areas requires extensive sampling and analysis. Reliable, road transportable, fully independent laboratory systems that could perform on-site a full range of analyses meeting high levels of quality assurance and control, would accelerate and thereby reduce the cost of cleanup and remediation efforts by (1) providing critical analytical data more rapidly, and (2) eliminating the handling, shipping, and manpower associated with sample shipments. Goals of RTAL are to meet the needs of DOE for rapid, accurate analysis of a wide variety of hazardous and radioactive contaminants in soil, groundwater, and surface waters. The system consists of a set of individual laboratory modules deployable independently or together, to meet specific site needs: radioanalytical lab, organic chemical analysis lab, inorganic chemical analysis lab, aquatic biomonitoring lab, field analytical lab, robotics base station, decontamination/sample screening module, and operations control center. Goal of this integrated system is a sample throughput of 20 samples/day, providing a full range of accurate analyses on each sample within 16 h (after sample preparation), compared with the 45- day turnaround time in commercial laboratories. A prototype RTAL consisting of 5 modules was built and demonstrated at Fernald(FEMP)`s OU-1 Waste Pits, during the 1st-3rd quarters of FY96 (including the `96 Blizzard). All performance and operational goals were met or exceeded: as many as 50 sample analyses/day were achieved, depending on the procedure, sample turnaround times were 50-67% less than FEMP`s best times, and RTAL costs were projected to be 30% less than FEMP costs for large volume analyses in fixed laboratories.

  15. Integrated mass transportation system study/definition/implementation program definition

    NASA Technical Reports Server (NTRS)

    Ransone, R. K.; Deptula, D. A.; Yorke, G. G.

    1975-01-01

    Specific actions needed to plan and effect transportation system improvements are identified within the constraints of limited financial, energy and land use resources, and diverse community requirements. A specific program is described which would develop the necessary generalized methodology for devising improved transportation systems and evaluate them against specific criteria for intermodal and intramodal optimization. A consistent, generalized method is provided for study and evaluation of transportation system improvements.

  16. The SIMPSONS project: An integrated Mars transportation system

    NASA Astrophysics Data System (ADS)

    Kaplan, Matthew; Carlson, Eric; Bradfute, Sherie; Allen, Kent; Duvergne, Francois; Hernandez, Bert; Le, David; Nguyen, Quan; Thornhill, Brett

    In response to the Request for Proposal (RFP) for an integrated transportation system network for an advanced Martian base, Frontier Transportation Systems (FTS) presents the results of the SIMPSONS project (Systems Integration for Mars Planetary Surface Operations Networks). The following topics are included: the project background, vehicle design, future work, conclusions, management status, and cost breakdown. The project focuses solely on the surface-to-surface transportation at an advanced Martian base.

  17. The SIMPSONS project: An integrated Mars transportation system

    NASA Technical Reports Server (NTRS)

    Kaplan, Matthew; Carlson, Eric; Bradfute, Sherie; Allen, Kent; Duvergne, Francois; Hernandez, Bert; Le, David; Nguyen, Quan; Thornhill, Brett

    1992-01-01

    In response to the Request for Proposal (RFP) for an integrated transportation system network for an advanced Martian base, Frontier Transportation Systems (FTS) presents the results of the SIMPSONS project (Systems Integration for Mars Planetary Surface Operations Networks). The following topics are included: the project background, vehicle design, future work, conclusions, management status, and cost breakdown. The project focuses solely on the surface-to-surface transportation at an advanced Martian base.

  18. Humic Acid Effects on the Transport of Colloidal Particles in Unsaturated Porous Media: Humic Acid Dosage, pH, and Ionic Strength Dependence

    NASA Astrophysics Data System (ADS)

    Morales, V. L.; Gao, B.; Steenhuis, T. S.

    2008-12-01

    Soil colloids and biocolloids can facilitate contaminant transport within the soil profile through the complexation of pollutants previously thought to have limited mobility. Dissolved organic substances are qualitatively known to alter the behavior of colloids and surface chemistry of soil particles in aquatic environments when adsorbed to their surfaces. Specifically, it has been observed that even small amounts of adsorbed humic acids result in a pronounced increase in colloid mobility in saturated porous systems, presumably by a combination of electrostatic and steric stabilization. However, the degree to which adsorbed humic acids stabilize colloidal suspension is highly sensitive to the system's solution chemistry; mainly in terms of pH, ionic strength, and metal ions present. The objective of this study is to expound quantitatively on the role that combined stabilizing and destabilizing solution chemistry components have on humic acid-colloid transport in unsaturated media by isolating experimentally some underlying mechanisms that regulate colloid transport in realistic aquatic systems. We hypothesize that in chemically heterogeneous porous media, with ionic strength values above 0 and pH ranges from 4 to 9, the effect of humic acid on colloid suspensions cannot be simply characterized by increased stability and mobility. That a critical salt concentration must exists for a given humic acid concentration and pH, above which the network of humic acid collapses by forming coordination complexes with other suspended or adsorbed humic acids, thus increasing greatly the retention of colloids in the porous medium by sweep flocculation. In addition, capillary forces in unsaturated media may contribute further to overcome repulsive forces that prevent flocculation of humic acid-colloid complexes. The experimental work in this study will include: jar tests to determine critical solution concentration combinations for desired coagulation/flocculation rates, column

  19. Role of ion transporters in the bile acid-induced esophageal injury.

    PubMed

    Laczkó, Dorottya; Rosztóczy, András; Birkás, Klaudia; Katona, Máté; Rakonczay, Zoltán; Tiszlavicz, László; Róka, Richárd; Wittmann, Tibor; Hegyi, Péter; Venglovecz, Viktória

    2016-07-01

    Barrett's esophagus (BE) is considered to be the most severe complication of gastro-esophageal reflux disease (GERD), in which the prolonged, repetitive episodes of combined acidic and biliary reflux result in the replacement of the squamous esophageal lining by columnar epithelium. Therefore, the acid-extruding mechanisms of esophageal epithelial cells (EECs) may play an important role in the defense. Our aim was to identify the presence of acid/base transporters on EECs and to investigate the effect of bile acids on their expressions and functions. Human EEC lines (CP-A and CP-D) were acutely exposed to bile acid cocktail (BAC) and the changes in intracellular pH (pHi) and Ca(2+) concentration ([Ca(2+)]i) were measured by microfluorometry. mRNA and protein expression of ion transporters was investigated by RT-PCR, Western blot, and immunohistochemistry. We have identified the presence of a Na(+)/H(+) exchanger (NHE), Na(+)/HCO3 (-) cotransporter (NBC), and a Cl(-)-dependent HCO3 (-) secretory mechanism in CP-A and CP-D cells. Acute administration of BAC stimulated HCO3 (-) secretion in both cell lines and the NHE activity in CP-D cells by an inositol triphosphate-dependent calcium release. Chronic administration of BAC to EECs increased the expression of ion transporters compared with nontreated cells. A similar expression pattern was observed in biopsy samples from BE compared with normal epithelium. We have shown that acute administration of bile acids differently alters ion transport mechanisms of EECs, whereas chronic exposure to bile acids increases the expression of acid/base transporters. We speculate that these adaptive processes of EECs represent an important mucosal defense against the bile acid-induced epithelial injury. PMID:27198194

  20. Bibliography for acid-rock drainage and selected acid-mine drainage issues related to acid-rock drainage from transportation activities

    USGS Publications Warehouse

    Bradley, Michael W.; Worland, Scott C.

    2015-01-01

    Acid-rock drainage occurs through the interaction of rainfall on pyrite-bearing formations. When pyrite (FeS2) is exposed to oxygen and water in mine workings or roadcuts, the mineral decomposes and sulfur may react to form sulfuric acid, which often results in environmental problems and potential damage to the transportation infrastructure. The accelerated oxidation of pyrite and other sulfidic minerals generates low pH water with potentially high concentrations of trace metals. Much attention has been given to contamination arising from acid mine drainage, but studies related to acid-rock drainage from road construction are relatively limited. The U.S. Geological Survey, in cooperation with the Tennessee Department of Transportation, is conducting an investigation to evaluate the occurrence and processes controlling acid-rock drainage and contaminant transport from roadcuts in Tennessee. The basic components of acid-rock drainage resulting from transportation activities are described and a bibliography, organized by relevant categories (remediation, geochemical, microbial, biological impact, and secondary mineralization) is presented.

  1. Recovery of Neisseria gonorrhoeae from 4 commercially available transport systems.

    PubMed

    Papp, John R; Henning, Tara; Khubbar, Manjeet; Kalve, Valdis; Bhattacharyya, Sanjib; Travanty, Emily; Xavier, Karen; Jones, Kelly; Rudrik, James T; Gaynor, Anne; Hagan, Celia

    2016-10-01

    Four commercial transport systems for the recovery of Neisseria gonorrhoeae were evaluated in support of the need to obtain culture isolates for the detection of antimicrobial resistance. Bacterial recovery from the InTray GC system was superior with minimal loss of viability in contrast to non-nutritive transport systems. PMID:27489119

  2. Characterization of the transport of. cap alpha. -methylaminoisobutyric acid by a human intestinal cell line (HT-29)

    SciTech Connect

    Bergin, L.; Dantzig, A.H.

    1986-03-01

    Under certain growth conditions, the human colon adenocarcinoma cell line HT-29 exhibits intestinal enterocyte-like properties. The differentiated cells possess a brush border with the enzyme markers (aminopeptidase and sucrase) normally associated with the intestine. To aid in the characterization of the transport properties of these cells, the uptake of a non-metabolizable amino acid analog, /sup 14/C-..cap alpha..-methylaminoisobutyric acid (MeAIB) as examined in the HT-29-Al subclone which possesses a brush border. The cells exhibited a time-dependent uptake of MeAIB which was concentrative and sodium-dependent. The pH optimum for uptake was about 7.8. Uptake was inhibited by low temperature, 1 mM ouabain, or 0.5 mM dinitrophenol. A 1 hr-preincubation of the cells in an isotonic KCl solution resulted in a decreased uptake rate, suggesting that a negative membrane potential is important for MeAIB uptake. The rate of 0.5 mM MeABIB uptake was inhibited by 40 to 90% by 5 mM of certain small neutral amino acids such as Ala, Ser, Pro, Gly, met but not by acidic or basic amino acids such as Asp, Glu, Arg or Lys. The uptake of MeAIB appears to be mediated by an amino acid transport carrier similar to the A-system described previously for Chinese hamster ovary cells.

  3. A Functional-Phylogenetic Classification System for Transmembrane Solute Transporters

    PubMed Central

    Saier, Milton H.

    2000-01-01

    A comprehensive classification system for transmembrane molecular transporters has been developed and recently approved by the transport panel of the nomenclature committee of the International Union of Biochemistry and Molecular Biology. This system is based on (i) transporter class and subclass (mode of transport and energy coupling mechanism), (ii) protein phylogenetic family and subfamily, and (iii) substrate specificity. Almost all of the more than 250 identified families of transporters include members that function exclusively in transport. Channels (115 families), secondary active transporters (uniporters, symporters, and antiporters) (78 families), primary active transporters (23 families), group translocators (6 families), and transport proteins of ill-defined function or of unknown mechanism (51 families) constitute distinct categories. Transport mode and energy coupling prove to be relatively immutable characteristics and therefore provide primary bases for classification. Phylogenetic grouping reflects structure, function, mechanism, and often substrate specificity and therefore provides a reliable secondary basis for classification. Substrate specificity and polarity of transport prove to be more readily altered during evolutionary history and therefore provide a tertiary basis for classification. With very few exceptions, a phylogenetic family of transporters includes members that function by a single transport mode and energy coupling mechanism, although a variety of substrates may be transported, sometimes with either inwardly or outwardly directed polarity. In this review, I provide cross-referencing of well-characterized constituent transporters according to (i) transport mode, (ii) energy coupling mechanism, (iii) phylogenetic grouping, and (iv) substrates transported. The structural features and distribution of recognized family members throughout the living world are also evaluated. The tabulations should facilitate familial and functional

  4. A functional-phylogenetic classification system for transmembrane solute transporters.

    PubMed

    Saier, M H

    2000-06-01

    A comprehensive classification system for transmembrane molecular transporters has been developed and recently approved by the transport panel of the nomenclature committee of the International Union of Biochemistry and Molecular Biology. This system is based on (i) transporter class and subclass (mode of transport and energy coupling mechanism), (ii) protein phylogenetic family and subfamily, and (iii) substrate specificity. Almost all of the more than 250 identified families of transporters include members that function exclusively in transport. Channels (115 families), secondary active transporters (uniporters, symporters, and antiporters) (78 families), primary active transporters (23 families), group translocators (6 families), and transport proteins of ill-defined function or of unknown mechanism (51 families) constitute distinct categories. Transport mode and energy coupling prove to be relatively immutable characteristics and therefore provide primary bases for classification. Phylogenetic grouping reflects structure, function, mechanism, and often substrate specificity and therefore provides a reliable secondary basis for classification. Substrate specificity and polarity of transport prove to be more readily altered during evolutionary history and therefore provide a tertiary basis for classification. With very few exceptions, a phylogenetic family of transporters includes members that function by a single transport mode and energy coupling mechanism, although a variety of substrates may be transported, sometimes with either inwardly or outwardly directed polarity. In this review, I provide cross-referencing of well-characterized constituent transporters according to (i) transport mode, (ii) energy coupling mechanism, (iii) phylogenetic grouping, and (iv) substrates transported. The structural features and distribution of recognized family members throughout the living world are also evaluated. The tabulations should facilitate familial and functional

  5. Imaging the L-Type Amino Acid Transporter-1 (LAT1) with Zr-89 ImmunoPET

    PubMed Central

    Ikotun, Oluwatayo F.; Marquez, Bernadette V.; Huang, Chaofeng; Masuko, Kazue; Daiji, Miyamoto; Masuko, Takashi; McConathy, Jonathan; Lapi, Suzanne E.

    2013-01-01

    The L-type amino acid transporter-1 (LAT1, SLC7A5) is upregulated in a wide range of human cancers, positively correlated with the biological aggressiveness of tumors, and a promising target for both imaging and therapy. Radiolabeled amino acids such as O-(2-[18F]fluoroethyl)-L-tyrosine (FET) that are transport substrates for system L amino acid transporters including LAT1 have met limited success for oncologic imaging outside of the brain, and thus new strategies are needed for imaging LAT1 in systemic cancers. Here, we describe the development and biological evaluation of a novel zirconium-89 labeled antibody, [89Zr]DFO-Ab2, targeting the extracellular domain of LAT1 in a preclinical model of colorectal cancer. This tracer demonstrated specificity for LAT1 in vitro and in vivo with excellent tumor imaging properties in mice with xenograft tumors. PET imaging studies showed high tumor uptake, with optimal tumor-to-non target contrast achieved at 7 days post administration. Biodistribution studies demonstrated tumor uptake of 10.5 ± 1.8 percent injected dose per gram (%ID/g) at 7 days with a tumor to muscle ratio of 13 to 1. In contrast, the peak tumor uptake of the radiolabeled amino acid [18F]FET was 4.4 ± 0.5 %ID/g at 30 min after injection with a tumor to muscle ratio of 1.4 to 1. Blocking studies with unlabeled anti-LAT1 antibody demonstrated a 55% reduction of [89Zr]DFO-Ab2 accumulation in the tumor at 7 days. These results are the first report of direct PET imaging of LAT1 and demonstrate the potential of immunoPET agents for imaging specific amino acid transporters. PMID:24143237

  6. Putative ABC transporter responsible for acetic acid resistance in Acetobacter aceti.

    PubMed

    Nakano, Shigeru; Fukaya, Masahiro; Horinouchi, Sueharu

    2006-01-01

    Two-dimensional gel electrophoretic analysis of the membrane fraction of Acetobacter aceti revealed the presence of several proteins that were produced in response to acetic acid. A 60-kDa protein, named AatA, which was mostly induced by acetic acid, was prepared; aatA was cloned on the basis of its NH2-terminal amino acid sequence. AatA, consisting of 591 amino acids and containing ATP-binding cassette (ABC) sequences and ABC signature sequences, belonged to the ABC transporter superfamily. The aatA mutation with an insertion of the neomycin resistance gene within the aatA coding region showed reduced resistance to acetic acid, formic acid, propionic acid, and lactic acid, whereas the aatA mutation exerted no effects on resistance to various drugs, growth at low pH (adjusted with HCl), assimilation of acetic acid, or resistance to citric acid. Introduction of plasmid pABC101 containing aatA under the control of the Escherichia coli lac promoter into the aatA mutant restored the defect in acetic acid resistance. In addition, pABC101 conferred acetic acid resistance on E. coli. These findings showed that AatA was a putative ABC transporter conferring acetic acid resistance on the host cell. Southern blot analysis and subsequent nucleotide sequencing predicted the presence of aatA orthologues in a variety of acetic acid bacteria belonging to the genera Acetobacter and Gluconacetobacter. The fermentation with A. aceti containing aatA on a multicopy plasmid resulted in an increase in the final yield of acetic acid.

  7. New mechanisms that regulate Saccharomyces cerevisiae short peptide transporter achieve balanced intracellular amino acid concentrations.

    PubMed

    Melnykov, Artem V

    2016-01-01

    The budding yeast Saccharomyces cerevisiae is able to take up large quantities of amino acids in the form of di- and tripeptides via a short peptide transporter, Ptr2p. It is known that PTR2 can be induced by certain peptides and amino acids, and the mechanisms governing this upregulation are understood at the molecular level. We describe two new opposing mechanisms of regulation that emphasize potential toxicity of amino acids: the first is upregulation of PTR2 in a population of cells, caused by amino acid secretion that accompanies peptide uptake; the second is loss of Ptr2p activity, due to transporter internalization following peptide uptake. Our findings emphasize the importance of proper amino acid balance in the cell and extend understanding of peptide import regulation in yeast.

  8. Transportation system requirements document. Revision 1 DCN01. Supplement

    SciTech Connect

    1995-05-01

    The original Transportation System Requirements Document described the functions to be performed by and the technical requirements for the Transportation System to transport spent nuclear fuel (SNF) and high-level radioactive waste (HLW) from Purchaser and Producer sites to a Civilian Radioactive Waste Management System (CRWMS) site, and between CRWMS sites. The purpose of that document was to define the system-level requirements. These requirements include design and operations requirements to the extent they impact on the development of the physical segments of Transportation. The document also presented an overall description of Transportation, its functions, its segments, and the requirements allocated to the segments and the system-level interfaces with Transportation. This revision of the document contains only the pages that have been modified.

  9. A Flexible Reusable Space Transportation System

    NASA Astrophysics Data System (ADS)

    Pietrobon, S. S.

    A crewless reusable vertical take-off horizontal landing space transportation system is investigated. The single stage launch vehicle goes into a very low orbit around the Earth. At burnout, the payload is deployed. At apogee, the upper stage fires to put the payload into its desired orbit. The launch vehicle continues in a single orbit of the Earth, re-entering the atmosphere and returning to the launch site. We call this near single stage to orbit (NSTO). For satellite payloads, the satellite and upper stage are carried in a reusable pod attached to the top of the vehicle. For crewed vehicles, the pod is replaced by a small winged vehicle which can be used for crew transfer and rescue from the International Space Station. This allows the launch vehicle to use a common bulkhead between the fuel and oxidiser tanks, further reducing launch vehicle mass. A number of propellant combinations are investigated. Computer simulations indicate that liquid oxygen with quadricyclene promises to give the largest payload mass for similar size vehicles. The launch vehicle can also be modified to be a fly- back booster for a heavy lift launch vehicle (HLLV). In this case the upper stage and payload are replaced with jet engines and kerosene fuel tanks. A pod is used to recover the second stage engines for reuse.

  10. Defective canalicular transport and toxicity of dietary ursodeoxycholic acid in the abcb11-/- mouse: transport and gene expression studies.

    PubMed

    Wang, Renxue; Liu, Lin; Sheps, Jonathan A; Forrest, Dana; Hofmann, Alan F; Hagey, Lee R; Ling, Victor

    2013-08-15

    The bile salt export pump (BSEP), encoded by the abcb11 gene, is the major canalicular transporter of bile acids from the hepatocyte. BSEP malfunction in humans causes bile acid retention and progressive liver injury, ultimately leading to end-stage liver failure. The natural, hydrophilic, bile acid ursodeoxycholic acid (UDCA) is efficacious in the treatment of cholestatic conditions, such as primary biliary cirrhosis and cholestasis of pregnancy. The beneficial effects of UDCA include promoting bile flow, reducing hepatic inflammation, preventing apoptosis, and maintaining mitochondrial integrity in hepatocytes. However, the role of BSEP in mediating UDCA efficacy is not known. Here, we used abcb11 knockout mice (abcb11-/-) to test the effects of acute and chronic UDCA administration on biliary secretion, bile acid composition, liver histology, and liver gene expression. Acutely infused UDCA, or its taurine conjugate (TUDC), was taken up by the liver but retained, with negligible biliary output, in abcb11-/- mice. Feeding UDCA to abcb11-/- mice led to weight loss, retention of bile acids, elevated liver enzymes, and histological damage to the liver. Semiquantitative RT-PCR showed that genes encoding Mdr1a and Mdr1b (canalicular) as well as Mrp4 (basolateral) transporters were upregulated in abcb11-/- mice. We concluded that infusion of UDCA and TUDC failed to induce bile flow in abcb11-/- mice. UDCA fed to abcb11-/- mice caused liver damage and the appearance of biliary tetra- and penta-hydroxy bile acids. Supplementation with UDCA in the absence of Bsep caused adverse effects in abcb11-/- mice. PMID:23764895

  11. Coupling of hydrologic transport and chemical reactions in a stream affected by acid mine drainage

    USGS Publications Warehouse

    Kimball, B.A.; Broshears, R.E.; Bencala, K.E.; McKnight, Diane M.

    1994-01-01

    Experiments in St. Kevin Gulch, an acid mine drainage stream, examined the coupling of hydrologic transport to chemical reactions affecting metal concentrations. Injection of LiCl as a conservative tracer was used to determine discharge and residence time along a 1497-m reach. Transport of metals downstream from inflows of acidic, metal-rich water was evaluated based on synoptic samples of metal concentrations and the hydrologic characteristics of the stream. Transport of SO4 and Mn was generally conservative, but in the subreaches most affected by acidic inflows, transport was reactive. Both 0.1-??m filtered and particulate Fe were reactive over most of the stream reach. Filtered Al partitioned to the particulate phase in response to high instream concentrations. Simulations that accounted for the removal of SO4, Mn, Fe, and Al with first-order reactions reproduced the steady-state profiles. The calculated rate constants for net removal used in the simulations embody several processes that occur on a stream-reach scale. The comparison between rates of hydrologie transport and chemical reactions indicates that reactions are only important over short distances in the stream near the acidic inflows, where reactions occur on a comparable time scale with hydrologic transport and thus affect metal concentrations.

  12. Isolation of a spontaneous CHO amino acid transport mutant by a combination of tritium suicide and replica plating

    SciTech Connect

    Dantzig, A.H.; Slayman, C.W.; Adelberg, E.A.

    1982-07-01

    A spontaneous transport mutant of Chinese hamster ovary cells, CHY-1, was isolated by a combination of (/sup 3/H)proline suicide and replica plating. The mutant took up less tritium than the parent, resulting in a lower killing rate during storage. Transport by four separate amino acid transport systems (A, ASC, L, Ly+) was examined. The CHY-1 mutant exhibited normal uptake via the ASC, L, and Ly+ systems. By contrast, uptake of the most specific substrate of the A system, 2-(methylamino)-isobutyric acid, was significantly reduced at low, but not high, concentrations, due to a 3.5-fold increase in Km and a 1.5-fold increase in Vmax. Taken together, these data suggest that the CHY-1 mutation may be in the structural gene coding for the A transport protein. The tritium suicide procedure is discussed, and general equations are derived to predict the maximum storage time for the survival of one mutant cell and the optimum size of the cell population for maximum mutant enrichment.

  13. Characterization of cationic amino acid transporters and expression of endothelial nitric oxide synthase in human placental microvascular endothelial cells.

    PubMed

    Dye, J F; Vause, S; Johnston, T; Clark, P; Firth, J A; D'Souza, S W; Sibley, C P; Glazier, J D

    2004-01-01

    We investigated the expression and activity of arginine transporters and endothelial nitric oxide synthase (eNOS) in human placental microvascular endothelial cells (HPMEC). Using RT-PCR amplification products for eNOS, CAT1, CAT2A, CAT2B, CAT4, 4F2hc (CD98), rBAT and the light chains y+LAT1, y+LAT2, and b0+T1 were detected in HPMEC, but not B0+. Immunohistochemistry and Western blotting confirmed the presence of 4F2hc and CAT1 protein in HPMEC. 4F2hc-light chain dimers were indicated by a shift in molecular mass detected under nonreducing conditions. L-Arginine transport into HPMEC was independent of Na+ or Cl- and was inhibited by the neutral amino acid glutamine, but not by cystine. The Ki for glutamine inhibition was greater in the absence of Na+. Kinetic analysis supported a two-transporter model attributed to system y+L and system y+. Expression of eNOS in HPMEC was detectable by immunohistochemistry and ELISA but not by Western blotting. Activity of eNOS in HPMEC, measured over 48 h, either as the basal production of nitric oxide (NO) or as the accumulation of intracellular cGMP was not detectable. We conclude that HPMEC transport cationic amino acids by systems y+ and y+L and that basal eNOS expression and activity in these cells is low. PMID:14597568

  14. Developing Intelligent Transportation Systems in an Integrated Systems Analysis Environment

    SciTech Connect

    Aceves, S M; Paddack, E

    2002-01-15

    We are working on developing an Integrated Systems Analysis Environment (ISAE) for application to analysis and optimization of Intelligent Transportation Systems (ITS). ISAE is based on the concept of Co-simulation, which allows the modeling of complex systems with extreme flexibility. Co-simulation allows the development of virtual ITS systems that can be analyzed and optimized as an overall integrated system. The virtual ITS system is defined by selecting different components from a component library. System component models can be written in multiple programming languages running on different computer platforms. At the same time, ISAE provides full protection for proprietary models. Co-simulation is a cost-effective alternative to competing methodologies, such as developing a translator or selecting a single programming language for all system components. Co-simulation has been recently demonstrated using an example of an automotive system. The demonstration was successfully performed. The paper describes plans on how to implement ISAE and Co-simulation to ITS, and the great advantages that this implementation would represent.

  15. The Fate and Transport of Glyphosate and its Degradation Product, Aminomethylphosphonic Acid (AMPA), in Water

    NASA Astrophysics Data System (ADS)

    Scribner, E.; Meyer, M. T.

    2006-05-01

    Since 2001, the U.S. Geological Survey (USGS) has investigated the fate and transport of glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), in surface water, and more recently in tile-drain flow, soil, and wet deposition. According to U.S. Environmental Protection Agency sources, glyphosate is among the world's most widely used herbicides. In 2004, glyphosate usage estimates indicated that between 103 and 113 million pounds were applied annually to crops in the United States. The use of glyphosate over a wide geographic area suggests that this herbicide might be a potential concern for air, water, and soil quality as well as measured in high concentrations in streams; therefore, it is important to monitor its fate and transport in ground-water/surface-water systems. National, regional, and field-scale studies conducted by the USGS National Water-Quality Assessment and Toxic Substance Hydrology Programs have studied the fate and transport of glyphosate in overland flow, tile- drain flow, surface water, soil, and wet-deposition samples. The samples were analyzed for glyphosate and AMPA by using derivatization and online solid-phase extraction with liquid chromatography/mass spectrometry (LC/MS) and LC/MS/MS methods developed by the USGS Organic Geochemistry Research Laboratory in Lawrence, Kansas. During spring, summer, and fall 2002 runoff periods in 50 Midwestern streams, glyphosate was detected at or above the 0.10 micrograms per liter detection limit in 35, 41, and 31 percent of samples, respectively. AMPA was detected in 53, 82, and 75 percent of samples, respectively. Results of 128 samples from a field study showed that glyphosate was transported as a narrow high- concentration pulse during the first period of runoff after application and that the concentration of glyphosate in runoff was greater than the concentration of AMPA. In tile-drain flow, glyphosate and AMPA were transported in a broad low-concentration pulse during these same

  16. Highly reusable space transportation system study

    SciTech Connect

    Haney, J.W.

    1997-01-01

    To significantly increase demand for launch services by stimulating existing and planned markets as well as enabling new markets, the cost to orbit needs to be reduced a factor of ten below projected Reusable Launch Vehicle (RLV) goals. This will place the recurring operations cost around {dollar_sign}200 per payload pound to low earth orbit (LEO). Methods for reducing the cost include: increasing relative vehicle performance, increasing vehicle reusability, and decreasing recurring operations. A study was conducted for NASA in support of its Highly Reusable Space Transportation (HRST) initiative to identify for further assessment and development, those launch strategies that hold the greatest potential with respect to meeting this goal. During this study a number of candidate strategies were evaluated associated with access to space. Both technical and cost trades were performed, and concluded that there are two airbreathing propulsion concepts utilizing launch assist that appear promising in achieving the HRST-cost goals. These concepts employ both turbine based combine cycle (TBCC) and rocket based combine cycle (RBCC) propulsion systems. The launch assist selected uses electromagnetic propulsion and a guideway to provide both delta velocity and altitude. A first order investigation of system level requirements associated with HRST launch assist for a magnetically launched vehicle including guideway concept and requirements as well as magnetic levitation and propulsion concepts and requirements were also conducted. This study concluded that the HRST goals of total recurring operations cost of {dollar_sign}200 per payload pound to Low Earth Orbit based on a ten year operational period were feasible if the required technology was matured. The most promising concept to achieve these goals is based on a RBCC powered vehicle with electromagnetic launch assist. {copyright} {ital 1997 American Institute of Physics.}

  17. Highly reusable space transportation system study

    NASA Astrophysics Data System (ADS)

    Haney, J. W.

    1997-01-01

    To significantly increase demand for launch services by stimulating existing and planned markets as well as enabling new markets, the cost to orbit needs to be reduced a factor of ten below projected Reusable Launch Vehicle (RLV) goals. This will place the recurring operations cost around 200 per payload pound to low earth orbit (LEO). Methods for reducing the cost include: increasing relative vehicle performance, increasing vehicle reusability, and decreasing recurring operations. A study was conducted for NASA in support of its Highly Reusable Space Transportation (HRST) initiative to identify for further assessment and development, those launch strategies that hold the greatest potential with respect to meeting this goal. During this study a number of candidate strategies were evaluated associated with access to space. Both technical and cost trades were performed, and concluded that there are two airbreathing propulsion concepts utilizing launch assist that appear promising in achieving the HRST-cost goals. These concepts employ both turbine based combine cycle (TBCC) and rocket based combine cycle (RBCC) propulsion systems. The launch assist selected uses electromagnetic propulsion and a guideway to provide both delta velocity and altitude. A first order investigation of system level requirements associated with HRST launch assist for a magnetically launched vehicle including guideway concept and requirements as well as magnetic levitation and propulsion concepts and requirements were also conducted. This study concluded that the HRST goals of total recurring operations cost of 200 per payload pound to Low Earth Orbit based on a ten year operational period were feasible if the required technology was matured. The most promising concept to achieve these goals is based on a RBCC powered vehicle with electromagnetic launch assist.

  18. A Segway RMP-based robotic transport system

    NASA Astrophysics Data System (ADS)

    Nguyen, Hoa G.; Kogut, Greg; Barua, Ripan; Burmeister, Aaron; Pezeshkian, Narek; Powell, Darren; Farrington, Nathan; Wimmer, Matt; Cicchetto, Brett; Heng, Chana; Ramirez, Velia

    2004-12-01

    In the area of logistics, there currently is a capability gap between the one-ton Army robotic Multifunction Utility/Logistics and Equipment (MULE) vehicle and a soldier"s backpack. The Unmanned Systems Branch at Space and Naval Warfare Systems Center (SPAWAR Systems Center, or SSC), San Diego, with the assistance of a group of interns from nearby High Tech High School, has demonstrated enabling technologies for a solution that fills this gap. A small robotic transport system has been developed based on the Segway Robotic Mobility Platform (RMP). We have demonstrated teleoperated control of this robotic transport system, and conducted two demonstrations of autonomous behaviors. Both demonstrations involved a robotic transporter following a human leader. In the first demonstration, the transporter used a vision system running a continuously adaptive mean-shift filter to track and follow a human. In the second demonstration, the separation between leader and follower was significantly increased using Global Positioning System (GPS) information. The track of the human leader, with a GPS unit in his backpack, was sent wirelessly to the transporter, also equipped with a GPS unit. The robotic transporter traced the path of the human leader by following these GPS breadcrumbs. We have additionally demonstrated a robotic medical patient transport capability by using the Segway RMP to power a mock-up of the Life Support for Trauma and Transport (LSTAT) patient care platform, on a standard NATO litter carrier. This paper describes the development of our demonstration robotic transport system and the various experiments conducted.

  19. Perfluoroalkyl Acid Concentrations in Blood Samples Subjected to Transportation and Processing Delay

    PubMed Central

    Bach, Cathrine Carlsen; Henriksen, Tine Brink; Bossi, Rossana; Bech, Bodil Hammer; Fuglsang, Jens; Olsen, Jørn; Nohr, Ellen Aagaard

    2015-01-01

    Background In studies of perfluoroalkyl acids, the validity and comparability of measured concentrations may be affected by differences in the handling of biospecimens. We aimed to investigate whether measured plasma levels of perfluoroalkyl acids differed between blood samples subjected to delay and transportation prior to processing and samples with immediate processing and freezing. Methods Pregnant women recruited at Aarhus University Hospital, Denmark, (n = 88) provided paired blood samples. For each pair of samples, one was immediately processed and plasma was frozen, and the other was delayed and transported as whole blood before processing and freezing of plasma (similar to the Danish National Birth Cohort). We measured 12 perfluoroalkyl acids and present results for compounds with more than 50% of samples above the lower limit of quantification. Results For samples taken in the winter, relative differences between the paired samples ranged between -77 and +38% for individual perfluoroalkyl acids. In most cases concentrations were lower in the delayed and transported samples, e.g. the relative difference was -29% (95% confidence interval -30; -27) for perfluorooctane sulfonate. For perfluorooctanoate there was no difference between the two setups [corresponding estimate 1% (0, 3)]. Differences were negligible in the summer for all compounds. Conclusions Transport of blood samples and processing delay, similar to conditions applied in some large, population-based studies, may affect measured perfluoroalkyl acid concentrations, mainly when outdoor temperatures are low. Attention to processing conditions is needed in studies of perfluoroalkyl acid exposure in humans. PMID:26356420

  20. Proton-dependent glutamine uptake by aphid bacteriocyte amino acid transporter ApGLNT1.

    PubMed

    Price, Daniel R G; Wilson, Alex C C; Luetje, Charles W

    2015-10-01

    Aphids house large populations of the gammaproteobacterial symbiont Buchnera aphidicola in specialized bacteriocyte cells. The combined biosynthetic capability of the holobiont (Acyrthosiphon pisum and Buchnera) is sufficient for biosynthesis of all twenty protein coding amino acids, including amino acids that animals alone cannot synthesize; and that are present at low concentrations in A. pisum's plant phloem sap diet. Collaborative holobiont amino acid biosynthesis depends on glutamine import into bacteriocytes, which serves as a nitrogen-rich amino donor for biosynthesis of other amino acids. Recently, we characterized A. pisum glutamine transporter 1 (ApGLNT1), a member of the amino acid/auxin permease family, as the dominant bacteriocyte plasma membrane glutamine transporter. Here we show ApGLNT1 to be structurally and functionally related to mammalian proton-dependent amino acid transporters (PATs 1-4). Using functional expression in Xenopus laevis oocytes, combined with two-electrode voltage clamp electrophysiology we demonstrate that ApGLNT1 is electrogenic and that glutamine induces large inward currents. ApGLNT1 glutamine induced currents are dependent on external glutamine concentration, proton (H+) gradient across the membrane, and membrane potential. Based on these transport properties, ApGLNT1-mediated glutamine uptake into A. pisum bacteriocytes can be regulated by changes in either proton gradients across the plasma membrane or membrane potential. PMID:26028424

  1. Humic acid transport in saturated porous media: influence of flow velocity and influent concentration.

    PubMed

    Wei, Xiaorong; Shao, Mingan; Du, Lina; Horton, Robert

    2014-12-01

    Understanding the transport of humic acids (HAs) in porous media can provide important and practical evidence needed for accurate prediction of organic/inorganic contaminant transport in different environmental media and interfaces. A series of column transport experiments was conducted to evaluate the transport of HA in different porous media at different flow velocities and influent HA concentrations. Low flow velocity and influent concentration were found to favor the adsorption and deposition of HA onto sand grains packed into columns and to give higher equilibrium distribution coefficients and deposition rate coefficients, which resulted in an increased fraction of HA being retained in columns. Consequently, retardation factors were increased and the transport of HA through the columns was delayed. These results suggest that the transport of HA in porous media is primarily controlled by the attachment of HA to the solid matrix. Accordingly, this attachment should be considered in studies of HA behavior in porous media.

  2. 21 CFR 862.1795 - Vanilmandelic acid test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Vanilmandelic acid test system. 862.1795 Section... Systems § 862.1795 Vanilmandelic acid test system. (a) Identification. A vanilmandelic acid test system is a device intended to measure vanilmandelic acid in urine. Measurements of vanilmandelic...

  3. Development trends in space transportation systems: From Hermes to Saenger

    NASA Astrophysics Data System (ADS)

    Vontein, Volker; Koelle, Dietrich E.

    The criteria for the development of future space transportation systems are given. A trend in reducing transportation costs by reutilizing transportation systems is outlined. The European Hermes project represents a first step towards reutilization and manned winged apparatus. The technological and organizational requirements and the German participation in this project are described. The Saenger concept is shown as a logical advancement of this project, and of the corresponding technology. It consists of a two stage winged space tug with horizontal launch. A space transportation system with low launching costs, higher safety, and mission flexibility is expected. It should complete cargo rocket Ariane 5.

  4. Variation in indole-3-acetic acid transport and its relationship with growth in etiolated lupin hypocotyls.

    PubMed

    Nicolás, Juana Inés López; Acosta, Manuel; Sánchez-Bravo, José

    2007-07-01

    The relationship between the variation in polar auxin transport (PAT) and elongating growth in etiolated Lupinus albus hypocotyls was investigated. Parameters of auxin transport, such as the amount transported, intensity of the transport and sensitivity to 1-N-naphthylphthalamic acid (NPA) inhibition were measured in isolated sections from different sites (apical, middle and basal) along the hypocotyls in seedlings of different ages. Auxin transport was studied by applying radioactive indole-3-acetic acid (IAA) to upright and inverted sections. Basipetal transport was much higher than acropetal and very sensitive to NPA inhibition, which indicates that transport is polarized. Polarity was expressed as the NPA-induced inhibition and the basipetal/acropetal ratio. As a rule, both the amount of IAA transported and the polarity varied with the age of the seedlings, with values increasing from 3 to 5d and then decreasing. Both parameters were higher in apical (where most growth is localized) than in middle and basal regions, although this longitudinal gradient tended to disappear with aging as hypocotyl growth slowed and finally ceased. The application of NPA did not modify hypocotyl elongation in 5-d-old intact seedlings. Derooting of the seedlings drastically reduced elongation in the control, while NPA partially restored the growth, which suggests that NPA induces an increase in auxin in the elongation region. These results suggest that a basipetally decreasing gradient in PAT along the hypocotyl, which changes with age, may be responsible for auxin distribution pattern controlling growth.

  5. Evidence of Two Functionally Distinct Ornithine Decarboxylation Systems in Lactic Acid Bacteria

    PubMed Central

    Romano, Andrea; Trip, Hein; Lonvaud-Funel, Aline; Lolkema, Juke S.

    2012-01-01

    Biogenic amines are low-molecular-weight organic bases whose presence in food can result in health problems. The biosynthesis of biogenic amines in fermented foods mostly proceeds through amino acid decarboxylation carried out by lactic acid bacteria (LAB), but not all systems leading to biogenic amine production by LAB have been thoroughly characterized. Here, putative ornithine decarboxylation pathways consisting of a putative ornithine decarboxylase and an amino acid transporter were identified in LAB by strain collection screening and database searches. The decarboxylases were produced in heterologous hosts and purified and characterized in vitro, whereas transporters were heterologously expressed in Lactococcus lactis and functionally characterized in vivo. Amino acid decarboxylation by whole cells of the original hosts was determined as well. We concluded that two distinct types of ornithine decarboxylation systems exist in LAB. One is composed of an ornithine decarboxylase coupled to an ornithine/putrescine transmembrane exchanger. Their combined activities results in the extracellular release of putrescine. This typical amino acid decarboxylation system is present in only a few LAB strains and may contribute to metabolic energy production and/or pH homeostasis. The second system is widespread among LAB. It is composed of a decarboxylase active on ornithine and l-2,4-diaminobutyric acid (DABA) and a transporter that mediates unidirectional transport of ornithine into the cytoplasm. Diamines that result from this second system are retained within the cytosol. PMID:22247134

  6. Sex-dependent activity of the spinal excitatory amino acid transporter: Role of estrous cycle.

    PubMed

    Sajjad, Jahangir; Felice, Valeria D; Golubeva, Anna V; Cryan, John F; O'Mahony, Siobhain M

    2016-10-01

    Females are more likely to experience visceral pain than males, yet mechanisms underlying this sex bias are not fully elucidated. Moreover, pain sensitivity can change throughout the menstrual cycle. Alterations in the glutamatergic system have been implicated in several pain-disorders; however, whether these are sex-dependent is unclear. Thus, we aimed to investigate sex differences in the spinal cord glutamate uptake and how it varies across the estrous cycle. The activity of the glutamate transporters, excitatory amino acid transporters (EAATs) was assessed using an ex vivo aspartate radioactive uptake assay in the lumbosacral spinal cord in Sprague-Dawley male and female rats. The gene expression of EAATs, glutamate receptor subunits NR1 and NR2B and the estrogen receptors ERα & ERβ in the spinal cord were also analyzed. EAAT activity was lower in females, particularly during the estrus phase, and this was the only cycle stage that was responsive to the pharmacological effects of the EAATs activator riluzole. Interestingly, EAAT1 mRNA expression was lower in high-estrogen and high-ERα states compared to diestrus in females. We conclude that the Spinal EAAT activity in females is different to that in males, and varies across the estrous cycle. Furthermore, the expression levels of estrogen receptors also showed a cycle-dependent pattern that may affect EAATs function and expression. PMID:27471194

  7. Recent Advance in the Relationship between Excitatory Amino Acid Transporters and Parkinson's Disease

    PubMed Central

    Zhang, Yunlong; Tan, Feng; Xu, Pingyi; Qu, Shaogang

    2016-01-01

    Parkinson's disease (PD) is the most common movement disorder disease in the elderly and is characterized by degeneration of dopamine neurons and formation of Lewy bodies. Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). If glutamate is not removed promptly in the synaptic cleft, it will excessively stimulate the glutamate receptors and induce excitotoxic effects on the CNS. With lack of extracellular enzyme to decompose glutamate, glutamate uptake in the synaptic cleft is mainly achieved by the excitatory amino acid transporters (EAATs, also known as high-affinity glutamate transporters). Current studies have confirmed that decreased expression and function of EAATs appear in PD animal models. Moreover, single unilateral administration of EAATs inhibitor in the substantia nigra mimics several PD features and this is a solid evidence supporting that decreased EAATs contribute to the process of PD. Drugs or treatments promoting the expression and function of EAATs are shown to attenuate dopamine neurons death in the substantia nigra and striatum, ameliorate the behavior disorder, and improve cognitive abilities in PD animal models. EAATs are potential effective drug targets in treatment of PD and thus study of relationship between EAATs and PD has predominant medical significance currently. PMID:26981287

  8. Carrier-mediated placental transport of cimetidine and valproic acid across differentiating JEG-3 cell layers.

    PubMed

    Ikeda, K; Ueda, C; Yamada, K; Nakamura, A; Hatsuda, Y; Kawanishi, S; Nishii, S; Ogawa, M

    2015-07-01

    Human choriocarcinoma has been used as a model to study trophoblast transcellular drug transport in the placenta. Previous models had limitations regarding low molecular weight drug transport through the intracellular gap junction. The purpose of this study was to evaluate placental carrier-mediated transport across a differentiating JEG-3 choriocarcinoma cell (DJEGs) layer model in which the intracellular gap junction was restricted. Cimetidine is the substrate of an efflux transporter, breast cancer resistance protein (BCRP). BCRP highly expressed in the placenta, and its function in the DJEGs model was investigated. In addition, the placental drug transport of another efflux transporter, multidrug resistance-associated proteins (MRPs), and an influx transporter, monocarboxylate transporter (MCT), were examined with various substrates. Cimetidine permeated from the fetal side to the maternal side at significantly high levels and saturated in a dose-dependent manner. The permeability coefficient of a MRP substrate, fluorescein, across the DJEGs model was significantly increased by inhibiting MRP function with probenecid. On the other hand, permeation in the influx direction to the fetal side with a substrate of MCT, valproic acid, had a gentle dose-dependent saturation. These findings suggest that the DJEGs model could be used to evaluate transcellular placental drug transport mediated by major placental transporters.

  9. Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids.

    PubMed

    Pineda, M; Fernández, E; Torrents, D; Estévez, R; López, C; Camps, M; Lloberas, J; Zorzano, A; Palacín, M

    1999-07-01

    We have identified a new human cDNA, L-amino acid transporter-2 (LAT-2), that induces a system L transport activity with 4F2hc (the heavy chain of the surface antigen 4F2, also named CD98) in oocytes. Human LAT-2 is the fourth member of the family of amino acid transporters that are subunits of 4F2hc. The amino acid transport activity induced by the co-expression of 4F2hc and LAT-2 was sodium-independent and showed broad specificity for small and large zwitterionic amino acids, as well as bulky analogs (e.g. BCH (2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid)). This transport activity was highly trans-stimulated, suggesting an exchanger mechanism of transport. Expression of tagged N-myc-LAT-2 alone in oocytes did not induce amino acid transport, and the protein had an intracellular location. Co-expression of N-myc-LAT-2 and 4F2hc gave amino acid transport induction and expression of N-myc-LAT-2 at the plasma membrane of the oocytes. These data suggest that LAT-2 is an additional member of the family of 4F2 light chain subunits, which associates with 4F2hc to express a system L transport activity with broad specificity for zwitterionic amino acids. Human LAT-2 mRNA is expressed in kidney > placenta > brain, liver > spleen, skeletal muscle, heart, small intestine, and lung. Human LAT-2 gene localizes at chromosome 14q11.2-13 (13 cR or approximately 286 kb from marker D14S1349). The high expression of LAT-2 mRNA in epithelial cells of proximal tubules, the basolateral location of 4F2hc in these cells, and the amino acid transport activity of LAT-2 suggest that this transporter contributes to the renal reabsorption of neutral amino acids in the basolateral domain of epithelial proximal tubule cells.

  10. Advanced transportation system study: Manned launch vehicle concepts for two way transportation system payloads to LEO

    NASA Technical Reports Server (NTRS)

    Duffy, James B.

    1993-01-01

    The purpose of the Advanced Transportation System Study (ATSS) task area 1 study effort is to examine manned launch vehicle booster concepts and two-way cargo transfer and return vehicle concepts to determine which of the many proposed concepts best meets NASA's needs for two-way transportation to low earth orbit. The study identified specific configurations of the normally unmanned, expendable launch vehicles (such as the National Launch System family) necessary to fly manned payloads. These launch vehicle configurations were then analyzed to determine the integrated booster/spacecraft performance, operations, reliability, and cost characteristics for the payload delivery and return mission. Design impacts to the expendable launch vehicles which would be required to perform the manned payload delivery mission were also identified. These impacts included the implications of applying NASA's man-rating requirements, as well as any mission or payload unique impacts. The booster concepts evaluated included the National Launch System (NLS) family of expendable vehicles and several variations of the NLS reference configurations to deliver larger manned payload concepts (such as the crew logistics vehicle (CLV) proposed by NASA JSC). Advanced, clean sheet concepts such as an F-1A engine derived liquid rocket booster (LRB), the single stage to orbit rocket, and a NASP-derived aerospace plane were also included in the study effort. Existing expendable launch vehicles such as the Titan 4, Ariane 5, Energia, and Proton were also examined. Although several manned payload concepts were considered in the analyses, the reference manned payload was the NASA Langley Research Center's HL-20 version of the personnel launch system (PLS). A scaled up version of the PLS for combined crew/cargo delivery capability, the HL-42 configuration, was also included in the analyses of cargo transfer and return vehicle (CTRV) booster concepts. In addition to strictly manned payloads, two-way cargo

  11. Advanced transportation system study: Manned launch vehicle concepts for two way transportation system payloads to LEO

    NASA Astrophysics Data System (ADS)

    Duffy, James B.

    1993-12-01

    The purpose of the Advanced Transportation System Study (ATSS) task area 1 study effort is to examine manned launch vehicle booster concepts and two-way cargo transfer and return vehicle concepts to determine which of the many proposed concepts best meets NASA's needs for two-way transportation to low earth orbit. The study identified specific configurations of the normally unmanned, expendable launch vehicles (such as the National Launch System family) necessary to fly manned payloads. These launch vehicle configurations were then analyzed to determine the integrated booster/spacecraft performance, operations, reliability, and cost characteristics for the payload delivery and return mission. Design impacts to the expendable launch vehicles which would be required to perform the manned payload delivery mission were also identified. These impacts included the implications of applying NASA's man-rating requirements, as well as any mission or payload unique impacts. The booster concepts evaluated included the National Launch System (NLS) family of expendable vehicles and several variations of the NLS reference configurations to deliver larger manned payload concepts (such as the crew logistics vehicle (CLV) proposed by NASA JSC). Advanced, clean sheet concepts such as an F-1A engine derived liquid rocket booster (LRB), the single stage to orbit rocket, and a NASP-derived aerospace plane were also included in the study effort. Existing expendable launch vehicles such as the Titan 4, Ariane 5, Energia, and Proton were also examined. Although several manned payload concepts were considered in the analyses, the reference manned payload was the NASA Langley Research Center's HL-20 version of the personnel launch system (PLS). A scaled up version of the PLS for combined crew/cargo delivery capability, the HL-42 configuration, was also included in the analyses of cargo transfer and return vehicle (CTRV) booster concepts. In addition to strictly manned payloads, two-way cargo

  12. Acid mine water aeration and treatment system

    DOEpatents

    Ackman, Terry E.; Place, John M.

    1987-01-01

    An in-line system is provided for treating acid mine drainage which basically comprises the combination of a jet pump (or pumps) and a static mixer. The jet pump entrains air into the acid waste water using a Venturi effect so as to provide aeration of the waste water while further aeration is provided by the helical vanes of the static mixer. A neutralizing agent is injected into the suction chamber of the jet pump and the static mixer is formed by plural sections offset by 90 degrees.

  13. Transport in small and/or random systems

    SciTech Connect

    Lax, M.

    1987-05-14

    This report discusses: transport in small systems; electron-phonon interactions in quantum wells; noise in small systems; laser propagation in the atmosphere; laser-aerosol interactions; transport properties of carriers in semiconductor quantum wells; light transmission in a particulate medium; and laser generation of shock waves in droplets. (LSP)

  14. Characteristics of Mammalian Rh Glycoproteins (SLC42 transporters) and Their Role in Acid-Base Transport

    PubMed Central

    Nakhoul, Nazih L.; Hamm, L. Lee

    2012-01-01

    The mammalian Rh glycoproteins belong to the solute transporter family SLC42 and include RhAG, present in red blood cells, and two non-erythroid members RhBG and RhCG that are expressed in various tissues, including kidney, liver, skin and the GI tract. The Rh proteins in the red blood cell form an “Rh complex” made up of one D-subunit, one CE-subunit and two RhAG subunits. The Rh complex has a well-known antigenic effect but also contributes to the stability of the red cell membrane. RhBG and RhCG are related to the NH4+ transporters of the yeast and bacteria but their exact function is yet to be determined. This review describes the expression and molecular properties of these membrane proteins and their potential role as NH3/NH4+ and CO2 transporters. The likelihood that these proteins transport gases such as CO2 or NH3 is novel and significant. The review also describes the physiological importance of these proteins and their relevance to human disease. PMID:23506896

  15. Transmembrane domain II of the human bile acid transporter SLC10A2 coordinates sodium translocation.

    PubMed

    Sabit, Hairat; Mallajosyula, Sairam S; MacKerell, Alexander D; Swaan, Peter W

    2013-11-01

    Human apical sodium-dependent bile acid transporter (hASBT, SLC10A2) is responsible for intestinal reabsorption of bile acids and plays a key role in cholesterol homeostasis. We used a targeted and systematic approach to delineate the role of highly conserved transmembrane helix 2 on the expression and function of hASBT. Cysteine mutation significantly depressed transport activity for >60% of mutants without affecting cell surface localization of the transporter. All mutants were inaccessible toward chemical modification by membrane-impermeant MTSET reagent, strongly suggesting that transmembrane 2 (TM2) plays an indirect role in bile acid substrate translocation. Both bile acid uptake and sodium dependence of TM2 mutants revealed a distinct α-helical periodicity. Kinetic studies with conservative and non-conservative mutants of sodium sensitive residues further underscored the importance of Gln(75), Phe(76), Met(79), Gly(83), Leu(86), Phe(90), and Asp(91) in hASBT function. Computational analysis indicated that Asp(91) may coordinate with sodium during the transport cycle. Combined, our data propose that a consortium of sodium-sensitive residues along with previously reported residues (Thr(134), Leu(138), and Thr(149)) from TM3 may form the sodium binding and translocation pathway. Notably, residues Gln(75), Met(79), Thr(82), and Leu(86) from TM2 are highly conserved in TM3 of a putative remote bacterial homologue (ASBTNM), suggesting a universal mechanism for the SLC10A transporter family.

  16. Tuning transport selectivity of ionic species by phosphoric acid gradient in positively charged nanochannel membranes.

    PubMed

    Yang, Meng; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Fan, Xin; Liu, Wei; Liu, Xizhen; Liu, Jianbo; Huang, Jin

    2015-02-01

    The transport of ionic species through a nanochannel plays important roles in fundamental research and practical applications of the nanofluidic device. Here, we demonstrated that ionic transport selectivity of a positively charged nanochannel membrane can be tuned under a phosphoric acid gradient. When phosphoric acid solution and analyte solution were connected by the positively charged nanochannel membrane, the faster-moving analyte through the positively charged nanochannel membrane was the positively charged dye (methylviologen, MV(2+)) instead of the negatively charged dye (1,5-naphthalene disulfonate, NDS(2-)). In other words, a reversed ion selectivity of the nanochannel membranes can be found. It can be explained as a result of the combination of diffusion, induced electroosmosis, and induced electrophoresis. In addition, the influencing factors of transport selectivity, including concentration of phosphoric acid, penetration time, and volume of feed solution, were also investigated. The results showed that the transport selectivity can further be tuned by adjusting these factors. As a method of tuning ionic transport selectivity by establishing phosphoric acid gradient, it will be conducive to improving the separation of ionic species. PMID:25557761

  17. Transport of plasma free fatty acids and triglycerides in man: a theoretical analysis

    PubMed Central

    Shames, David M.; Frank, Arthur; Steinberg, Daniel; Berman, Mones

    1970-01-01

    Three different multicompartmental models of free fatty acid (FFA) and very low density lipoprotein triglyceride fatty acid (VLDL-TGFA) transport in man are formulated from plasma FFA and VLDL-TGFA tracee and tracer data collected over a 24 hr interval after the injection of palmitate-14C. All modeling and data fitting were performed on a digital computer using the SAAM program. Structural differences in the three models relate to the position of the slowly turning over compartment required to generate the late portion of the plasma VLDL-TGFA tracer data. The positions of this slow compartment are along the hepatic pathway from FFA to VLDL-TGFA (model A) or in the distribution system of VLDL-TGFA (model B) or in the distribution system of FFA (model C). Although all three models are equally consistent with our experimental data and are supported by observations of others, each reveals inconsistency with some data obtained from the literature. Consequently, a combination model of FFA-TGFA transport, incorporating properties of models A, B, and C would be more consistent with all available data. Experiments that would help to determine the quantitative significance of each of the slow compartments in the combination model are suggested. Several other models suggesting recycling of plasma VLDL-TGFA through the plasma FFA pool, kinetic heterogencity of the plasma VLDL-TGFA pool, and contamination of plasma VLDL-TGFA radioactivity with low density lipoprotein (LDL) TGFA radioactivity were tested. The first model does not explain the late portion of the plasma VLDL-TGFA tracer data. The second and third models, while consistent with our tracee and tracer data, have steady-state implications with respect to the extent of kinetic heterogeneity and size of the LDL-TGFA contaminant that make them unlikely. Assumptions underlying other investigator's models of FFA and TGFA transport in man are reviewed within the logical framework of our models. Quantitative differences among

  18. Computational modelling of placental amino acid transfer as an integrated system.

    PubMed

    Panitchob, N; Widdows, K L; Crocker, I P; Johnstone, E D; Please, C P; Sibley, C P; Glazier, J D; Lewis, R M; Sengers, B G

    2016-07-01

    Placental amino acid transfer is essential for fetal development and its impairment is associated with poor fetal growth. Amino acid transfer is mediated by a broad array of specific plasma membrane transporters with overlapping substrate specificity. However, it is not fully understood how these different transporters work together to mediate net flux across the placenta. Therefore the aim of this study was to develop a new computational model to describe how human placental amino acid transfer functions as an integrated system. Amino acid transfer from mother to fetus requires transport across the two plasma membranes of the placental syncytiotrophoblast, each of which contains a distinct complement of transporter proteins. A compartmental modelling approach was combined with a carrier based modelling framework to represent the kinetics of the individual accumulative, exchange and facilitative classes of transporters on each plasma membrane. The model successfully captured the principal features of transplacental transfer. Modelling results clearly demonstrate how modulating transporter activity and conditions such as phenylketonuria, can increase the transfer of certain groups of amino acids, but that this comes at the cost of decreasing the transfer of others, which has implications for developing clinical treatment options in the placenta and other transporting epithelia. PMID:27045077

  19. Reactive iron transport in an acidic mountain stream in Summit County, Colorado: A hydrologic perspective

    USGS Publications Warehouse

    McKnight, Diane M.; Bencala, K.E.

    1989-01-01

    A pH perturbation experiment was conducted in an acidic, metal-enriched, mountain stream to identify relative rates of chemical and hydrologic processes as they influence iron transport. During the experiment the pH was lowered from 4.2 to 3.2 for three hours by injection of sulfuric acid. Amorphous iron oxides are abundant on the streambed, and dissolution and photoreduction reactions resulted in a rapid increase in the dissolved iron concentration. The increase occurred simultaneously with the decrease in pH. Ferrous iron was the major aqueous iron species. The changes in the iron concentration during the experiment indicate that variation exists in the solubility properties of the hydrous iron oxides on the streambed with dissolution of at least two compartments of hydrous iron oxides contributing to the iron pulse. Spatial variations of the hydrologic properties along the stream were quantified by simulating the transport of a coinjected tracer, lithium. A simulation of iron transport, as a conservative solute, indicated that hydrologie transport had a significant role in determining downstream changes in the iron pulse. The rapidity of the changes in iron concentration indicates that a model based on dynamic equilibrium may be adequate for simulating iron transport in acid streams. A major challenge for predictive solute transport models of geochemical processes may be due to substantial spatial and seasonal variations in chemical properties of the reactive hydrous oxides in such streams, and in the physical and hydrologic properties of the stream. ?? 1989.

  20. The role of EPA`s Acid Rain Division in the Ozone Transport Commission`s NOx budget program

    SciTech Connect

    Schary, C.; Culligan, K.

    1997-12-31

    The Ozone Transport Commission`s (OTC) Nitrogen Oxides (NO{sub x}) Budget Program will implement the emissions reduction goal of the 1994 Memorandum of Understanding between its twelve member states and the District of Columbia. The program will achieve its significant NO{sub x} reductions from electric utilities and industrial boilers using a {open_quotes}cap-and-trade{close_quotes} approach modeled after the US Environmental Protection Agency`s sulfur dioxide emissions trading under the Acid Rain Program. The similarity of the two programs has led to the development of an important partnership between the OTC states and EPA`s Acid Rain Division, Over the past two years, Acid Rain Program staff have shared their technical expertise and assisted extensively in the development of the program`s rules. Leveraging the investment EPA made in the systems used to run the Acid Rain Program, the OTC states have asked the Acid Rain Division to administer the data systems for them, and together are working to expand its existing Emissions Tracking System and to modify a clone of the sulfur dioxide Allowance Tracking System, to fulfill the unique requirements of the NO{sub x} Budget Program. This partnership is an important example of the new type of cooperation and sharing of expertise and resources that should develop between EPA and states as they launch multi-state programs to address regional pollution problems that defy a single-state solution.

  1. Transport and Metabolism of 1-Aminocyclopropane-1-carboxylic Acid in Sunflower (Helianthus annuus L.) Seedlings 1

    PubMed Central

    Finlayson, Scott A.; Foster, Kenneth R.; Reid, David M.

    1991-01-01

    Transport and metabolism of [2,3-14C] 1-aminocyclopropane-1-carboxylic acid (ACC) from roots to shoots in 4-day-old sunflower (Helianthus annuus L.) seedlings were studied. [14C]ACC was detected in, and 14C2H4 was evolved from, shoots 0.5 hours after [14C]ACC was supplied to roots. Ethylene emanation from the shoots returned to normal levels after 6 hours. The roots showed a similar pattern, although at 24 hours ethylene emanation was still slightly higher than in those plants that did not receive ACC. [14C]N-malonyl-ACC (MACC) was detected in both tissues at all times sampled. [14C]MACC levels surpassed [14C]ACC levels in the shoot at 2 hours, whereas [14C]MACC levels in the root remained below [14C]ACC levels until 6 hours, after which they were higher. Thin-layer chromatography analysis identified [14C] ACC in 1-hour shoot extracts, and [14C]MACC was identified in root tissues at 1 and 12 hours after treatment. [14C]ACC and [14C] MACC in the xylem sap of treated seedlings were identified by thin-layer chromatography. Xylem transport of [14C]ACC in treated seedlings, and transport of ACC in untreated seedlings, was confirmed by gas chromatography-mass spectrometry. Some evidence for the presence of [14C]MACC in xylem sap in [14C]ACC-treated seedlings is presented. A substantial amount of radioactivity in both ACC and MACC fractions was detected leaking from the roots over 24 hours. A second radiolabeled volatile compound was trapped in a CO2-trapping solution but not in mercuric perchlorate. Levels of this compound were highest after the peak of ACC levels and before peak MACC levels in both tissues, suggesting that an alternate pathway of ACC metabolism was operating in this system. PMID:16668342

  2. Efficient Transport of Nitric Acid in Urban Plumes Observed Over the North Atlantic Ocean

    NASA Astrophysics Data System (ADS)

    Neuman, J.; Parrish, D.; Trainer, M.; Brown, S.; Fehsenfeld, F.; Flocke, F.; Holloway, J.; Nowak, J.; Ryerson, T.; Stark, H.; Swanson, A.

    2005-12-01

    The processing of anthropogenic NOx emissions from urban and industrial sources was studied using data collected from an instrumented aircraft flying over the east coast of the United States and over the North Atlantic Ocean. Pollutants were sampled from the National Oceanic and Atmospheric Administration WP-3 aircraft during the International Consortium for Atmospheric Research on Transport and Transformation study in July and August, 2004. Fast response measurements of reactive nitrogen compounds and carbon monoxide (CO) were obtained in crosswind transects of urban plumes in the New York City and Boston source regions and up to 1600 km downwind. The magnitude and geographical extent of the effects of NOx and its oxidation products depend on the NOx oxidation rates and pathways and on the atmospheric lifetime and loss mechanisms of the resulting secondary products. In urban plumes that were sampled further than 200 km from New York City and Boston, nitric acid was always the most abundant reactive nitrogen species and usually accounted for over 80% of the sum of NOx and its oxidation products. During this study, frequently plumes were transported above the marine boundary layer at a few hundred meters altitude and were decoupled from the surface, which allowed efficient transport of nitric acid that is not commonly observed at the surface, in the continental boundary layer, or in the free troposphere. In plumes observed over the remote North Atlantic Ocean, nitric acid mixing ratios were high (up to 50 ppbv) and the ratio of CO to reactive nitrogen changed little with plume age, reflecting the small depositional loss of nitric acid. Many of the photochemically aged urban plumes were characterized by the presence of tens of ppbv of nitric acid for several days. As a consequence of the slow removal of nitric acid from these air masses, NOx can be reformed from nitric acid photolysis and OH oxidation. The efficient transport of nitric acid may also allow for

  3. Cryogenic Transport of High-Pressure-System Recharge Gas

    NASA Technical Reports Server (NTRS)

    Ungar, Eugene K,; Ruemmele, Warren P.; Bohannon, Carl

    2010-01-01

    A method of relatively safe, compact, efficient recharging of a high-pressure room-temperature gas supply has been proposed. In this method, the gas would be liquefied at the source for transport as a cryogenic fluid at or slightly above atmospheric pressure. Upon reaching the destination, a simple heating/expansion process would be used to (1) convert the transported cryogenic fluid to the room-temperature, high-pressure gaseous form in which it is intended to be utilized and (2) transfer the resulting gas to the storage tank of the system to be recharged. In conventional practice for recharging high-pressure-gas systems, gases are transported at room temperature in high-pressure tanks. For recharging a given system to a specified pressure, a transport tank must contain the recharge gas at a much higher pressure. At the destination, the transport tank is connected to the system storage tank to be recharged, and the pressures in the transport tank and the system storage tank are allowed to equalize. One major disadvantage of the conventional approach is that the high transport pressure poses a hazard. Another disadvantage is the waste of a significant amount of recharge gas. Because the transport tank is disconnected from the system storage tank when it is at the specified system recharge pressure, the transport tank still contains a significant amount of recharge gas (typically on the order of half of the amount transported) that cannot be used. In the proposed method, the cryogenic fluid would be transported in a suitably thermally insulated tank that would be capable of withstanding the recharge pressure of the destination tank. The tank would be equipped with quick-disconnect fluid-transfer fittings and with a low-power electric heater (which would not be used during transport). In preparation for transport, a relief valve would be attached via one of the quick-disconnect fittings (see figure). During transport, the interior of the tank would be kept at a near

  4. Docosahexaenoic acid in neural signaling systems.

    PubMed

    Crawford, Michael A

    2006-01-01

    Docosahexaenoic acid has been conserved in neural signalling systems in the cephalopods, fish, amphibian, reptiles, birds, mammals, primates and humans. This extreme conservation, despite wide genomic changes over 500 million years, testifies to a uniqueness of this molecule in the brain. The brain selectively incorporates docosahexaenoic acid and its rate of incorporation into the developing brain has been shown to be greater than ten times more efficient than its synthesis from the omega 3 fatty acids of land plant origin. Data has now been published demonstrating a significant influence of dietary omega 3 fatty acids on neural gene expression. As docosahexaenoic acid is the only omega 3 fatty acid in the brain, it is likely that it is the ligand involved. The selective uptake, requirement for function and stimulation of gene expression would have conferred an advantage to a primate which separated from the chimpanzees in the forests and woodlands and sought a different ecological niche. In view of the paucity of docosahexaenoic acid in the land food chain it is likely that the advantage would have been gained from a lacustrine or marine coastal habitat with access to food rich in docosahexaenoic acid and the accessory micronutrients, such as iodine, zinc, copper, manganese and selenium, of importance in brain development and protection against peroxidation. Land agricultural development has, in recent time, come to dominate the human food chain. The decline in use and availability of aquatic resources is not considered important by Langdon (2006) as he considers the resource was not needed for human evolution and can be replaced from the terrestrial food chain. This notion is not supported by the biochemistry nor the molecular biology. He misses the point that the shoreline hypothesis is not just dependent on docosahexaenoic acid but also on the other accessory nutrients specifically required by the brain. Moreover he neglects the basic principle of Darwinian

  5. 21 CFR 862.1509 - Methylmalonic acid (nonquantitative) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Test Systems § 862.1509 Methylmalonic acid (nonquantitative) test system. (a) Identification. A methylmalonic acid (nonquantitative) test system is a device intended to identify methylmalonic acid in urine... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Methylmalonic acid (nonquantitative) test...

  6. 21 CFR 862.1509 - Methylmalonic acid (nonquantitative) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Test Systems § 862.1509 Methylmalonic acid (nonquantitative) test system. (a) Identification. A methylmalonic acid (nonquantitative) test system is a device intended to identify methylmalonic acid in urine... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Methylmalonic acid (nonquantitative) test...

  7. 21 CFR 862.1509 - Methylmalonic acid (nonquantitative) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Test Systems § 862.1509 Methylmalonic acid (nonquantitative) test system. (a) Identification. A methylmalonic acid (nonquantitative) test system is a device intended to identify methylmalonic acid in urine... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Methylmalonic acid (nonquantitative) test...

  8. 21 CFR 862.1775 - Uric acid test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Uric acid test system. 862.1775 Section 862.1775....1775 Uric acid test system. (a) Identification. A uric acid test system is a device intended to measure uric acid in serum, plasma, and urine. Measurements obtained by this device are used in the...

  9. 21 CFR 862.1775 - Uric acid test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Uric acid test system. 862.1775 Section 862.1775....1775 Uric acid test system. (a) Identification. A uric acid test system is a device intended to measure uric acid in serum, plasma, and urine. Measurements obtained by this device are used in the...

  10. Transport processes in biological systems: Tumoral cells and human brain

    NASA Astrophysics Data System (ADS)

    Lucia, Umberto

    2014-01-01

    The entropy generation approach has been developed for the analysis of complex systems, with particular regards to biological systems, in order to evaluate their stationary states. The entropy generation is related to the transport processes related to exergy flows. Moreover, cancer can be described as an open complex dynamic and self-organizing system. Consequently, it is used as an example useful to evaluate the different thermo-chemical quantities of the transport processes in normal and in tumoral cells systems.

  11. Transport and metabolism of fumaric acid in Saccharomyces cerevisiae in aerobic glucose-limited chemostat culture.

    PubMed

    Shah, Mihir V; van Mastrigt, Oscar; Heijnen, Joseph J; van Gulik, Walter M

    2016-04-01

    Currently, research is being focused on the industrial-scale production of fumaric acid and other relevant organic acids from renewable feedstocks via fermentation, preferably at low pH for better product recovery. However, at low pH a large fraction of the extracellular acid is present in the undissociated form, which is lipophilic and can diffuse into the cell. There have been no studies done on the impact of high extracellular concentrations of fumaric acid under aerobic conditions in S. cerevisiae, which is a relevant issue to study for industrial-scale production. In this work we studied the uptake and metabolism of fumaric acid in S. cerevisiae in glucose-limited chemostat cultures at a cultivation pH of 3.0 (pH < pK). Steady states were achieved with different extracellular levels of fumaric acid, obtained by adding different amounts of fumaric acid to the feed medium. The experiments were carried out with the wild-type S. cerevisiae CEN.PK 113-7D and an engineered S. cerevisiae ADIS 244 expressing a heterologous dicarboxylic acid transporter (DCT-02) from Aspergillus niger, to examine whether it would be capable of exporting fumaric acid. We observed that fumaric acid entered the cells most likely via passive diffusion of the undissociated form. Approximately two-thirds of the fumaric acid in the feed was metabolized together with glucose. From metabolic flux analysis, an increased ATP dissipation was observed only at high intracellular concentrations of fumarate, possibly due to the export of fumarate via an ABC transporter. The implications of our results for the industrial-scale production of fumaric acid are discussed. PMID:26683700

  12. Modeling uranium transport in acidic contaminated groundwater with base addition

    SciTech Connect

    Zhang, Fan; Luo, Wensui; Parker, Jack C.; Brooks, Scott C; Watson, David B; Jardine, Philip; Gu, Baohua

    2011-01-01

    This study investigates reactive transport modeling in a column of uranium(VI)-contaminated sediments with base additions in the circulating influent. The groundwater and sediment exhibit oxic conditions with low pH, high concentrations of NO{sub 3}{sup -}, SO{sub 4}{sup 2-}, U and various metal cations. Preliminary batch experiments indicate that additions of strong base induce rapid immobilization of U for this material. In the column experiment that is the focus of the present study, effluent groundwater was titrated with NaOH solution in an inflow reservoir before reinjection to gradually increase the solution pH in the column. An equilibrium hydrolysis, precipitation and ion exchange reaction model developed through simulation of the preliminary batch titration experiments predicted faster reduction of aqueous Al than observed in the column experiment. The model was therefore modified to consider reaction kinetics for the precipitation and dissolution processes which are the major mechanism for Al immobilization. The combined kinetic and equilibrium reaction model adequately described variations in pH, aqueous concentrations of metal cations (Al, Ca, Mg, Sr, Mn, Ni, Co), sulfate and U(VI). The experimental and modeling results indicate that U(VI) can be effectively sequestered with controlled base addition due to sorption by slowly precipitated Al with pH-dependent surface charge. The model may prove useful to predict field-scale U(VI) sequestration and remediation effectiveness.

  13. Modeling uranium transport in acidic contaminated groundwater with base addition.

    PubMed

    Zhang, Fan; Luo, Wensui; Parker, Jack C; Brooks, Scott C; Watson, David B; Jardine, Philip M; Gu, Baohua

    2011-06-15

    This study investigates reactive transport modeling in a column of uranium(VI)-contaminated sediments with base additions in the circulating influent. The groundwater and sediment exhibit oxic conditions with low pH, high concentrations of NO(3)(-), SO(4)(2-), U and various metal cations. Preliminary batch experiments indicate that additions of strong base induce rapid immobilization of U for this material. In the column experiment that is the focus of the present study, effluent groundwater was titrated with NaOH solution in an inflow reservoir before reinjection to gradually increase the solution pH in the column. An equilibrium hydrolysis, precipitation and ion exchange reaction model developed through simulation of the preliminary batch titration experiments predicted faster reduction of aqueous Al than observed in the column experiment. The model was therefore modified to consider reaction kinetics for the precipitation and dissolution processes which are the major mechanism for Al immobilization. The combined kinetic and equilibrium reaction model adequately described variations in pH, aqueous concentrations of metal cations (Al, Ca, Mg, Sr, Mn, Ni, Co), sulfate and U(VI). The experimental and modeling results indicate that U(VI) can be effectively sequestered with controlled base addition due to sorption by slowly precipitated Al with pH-dependent surface charge. The model may prove useful to predict field-scale U(VI) sequestration and remediation effectiveness.

  14. The importance of glutamate, glycine, and {gamma}-aminobutyric acid transport and regulation in manganese, mercury and lead neurotoxicity

    SciTech Connect

    Fitsanakis, Vanessa A.; Aschner, Michael . E-mail: michael.aschner@vanderbilt.edu

    2005-05-01

    Historically, amino acids were studied in the context of their importance in protein synthesis. In the 1950s, the focus of research shifted as amino acids were recognized as putative neurotransmitters. Today, many amino acids are considered important neurochemicals. Although many amino acids play a role in neurotransmission, glutamate (Glu), glycine (Gly), and {gamma}-aminobutyric acid (GABA) are among the more prevalent and better understood. Glu, the major excitatory neurotransmitter, and Gly and GABA, the major inhibitory neurotransmitters, in the central nervous system, are known to be tightly regulated. Prolonged exposure to environmental toxicants, such as manganese (Mn), mercury (Hg), or lead (Pb), however, can lead to dysregulation of these neurochemicals and subsequent neurotoxicity. While the ability of these metals to disrupt the regulation of Glu, Gly and GABA have been studied, few articles have examined the collective role of these amino acids in the respective metal's mechanism of toxicity. For each of the neurotransmitters above, we will provide a brief synopsis of their regulatory function, including the importance of transport and re-uptake in maintaining their optimal function. Additionally, the review will address the hypothesis that aberrant homeostasis of any of these amino acids, or a combination of the three, plays a role in the neurotoxicity of Mn, Hg, or Pb.

  15. Pharmacokinetics of amino acid ester prodrugs of acyclovir after oral administration: interaction with the transporters on Caco-2 cells.

    PubMed

    Katragadda, Suresh; Jain, Ritesh; Kwatra, Deep; Hariharan, Sudharshan; Mitra, Ashim K

    2008-10-01

    In vivo systemic absorption of the amino acid prodrugs of acyclovir (ACV) after oral administration was evaluated in rats. Stability of the prodrugs, L-alanine-ACV (AACV), L-serine-ACV (SACV), L-isoleucine-ACV (IACV), gamma-glutamate-ACV (EACV) and L-valine-ACV (VACV) was evaluated in various tissues. Interaction of these prodrugs with the transporters on Caco-2 cells was studied. In vivo systemic bioavailability of these prodrugs upon oral administration was evaluated in jugular vein cannulated rats. The amino acid ester prodrugs showed affinity towards various amino acid transporters as well as the peptide transporter on the Caco-2 cells. In terms of stability, EACV was most enzymatically stable compared to other prodrugs especially in liver homogenate. In oral absorption studies, ACV and AACV showed high terminal elimination rate constants (lambda(z)). SACV and VACV exhibited approximately five-fold increase in area under the curve (AUC) values relative to ACV (p<0.05). C(max(T)) (maximum concentration) of SACV was observed to be 39+/-22 microM in plasma which is 2 times better than VACV and 15 times better than ACV. C(last(T)) (concentration at the last time point) of SACV was observed to be 0.18+/-0.06 microM in plasma which is two times better than VACV and three times better than ACV. Amino acid ester prodrugs of ACV were absorbed at varying amounts (C(max)) and eliminated at varying rates (lambda(z)) thereby leading to varying extents (AUC). The amino acid ester prodrug SACV owing to its enhanced stability, higher AUC and better concentration at last time point seems to be a promising candidate for the oral treatment of herpes infections.

  16. Models for gibberellic acid transport and enzyme production and transport in the aleurone layer of barley.

    PubMed

    O'Brien, Ricky; Fowkes, Nev; Bassom, Andrew P

    2010-11-01

    Gibberellins are growth hormones produced in the embryo of grain released during germination. They promote growth through the production of enzymes in the aleurone layer surrounding the endosperm. These enzymes then diffuse into the endosperm and produce the sugars required by the growing acrospire. Here we model the transport of gibberellins into and along the aleurone layer, the consequent production of enzymes, and their transport into the endosperm. Simple approximate solutions of the governing equations are obtained which suggest that the enzymes are released immediately behind a gibberellin front which travels with almost constant speed along the aleurone layer. The model also suggests that this propagation speed is determined primarily by conditions near the scutellum-aleurone junction, which may enable the embryo to actively control the germination process.

  17. Detection and characterization of carrier-mediated cationic amino acid transport in lysosomes of normal and cystinotic human fibroblasts. Role in therapeutic cystine removal

    SciTech Connect

    Pisoni, R.L.; Thoene, J.G.; Christensen, H.N.

    1985-04-25

    The discovery of a trans-stimulation property associated with lysine exodus from lysosomes of human fibroblasts has enabled us to characterize a system mediating the transport of cationic amino acids across the lysosomal membrane of human fibroblasts. The cationic amino acids arginine, lysine, ornithine, diaminobutyrate, histidine, 2-aminoethylcysteine, and the mixed disulfide of cysteine and cysteamine all caused trans-stimulation of the exodus of radiolabeled lysine from the lysosomal fraction of human fibroblasts at pH 6.5. In contrast, neutral and acidic amino acids did not affect the rate of lysine exodus. Trans-stimulation of lysine exodus was observed over the pH range from 5.5 to 7.6, was specific for the L-isomer of the cationic amino acid, and was intolerant to methylation of the alpha-amino group of the amino acid. The lysosomotropic amine, chloroquine, greatly retarded lysine exodus, whereas the presence of sodium ion was without effect. The specificity and lack of Na+ dependence of this lysosomal transport system is similar to that of System y+ present on the plasma membrane of human fibroblasts. An important mechanism by which cysteamine treatment of cystinosis allows cystine escape from lysosomes may be the ability of the mixed disulfide of cysteine and cysteamine formed by sulfhydryl-disulfide exchange to migrate by this newly discovered system mediating cationic amino acid transport.

  18. TransportDB: a comprehensive database resource for cytoplasmic membrane transport systems and outer membrane channels.

    PubMed

    Ren, Qinghu; Chen, Kaixi; Paulsen, Ian T

    2007-01-01

    TransportDB (http://www.membranetransport.org/) is a comprehensive database resource of information on cytoplasmic membrane transporters and outer membrane channels in organisms whose complete genome sequences are available. The complete set of membrane transport systems and outer membrane channels of each organism are annotated based on a series of experimental and bioinformatic evidence and classified into different types and families according to their mode of transport, bioenergetics, molecular phylogeny and substrate specificities. User-friendly web interfaces are designed for easy access, query and download of the data. Features of the TransportDB website include text-based and BLAST search tools against known transporter and outer membrane channel proteins; comparison of transporter and outer membrane channel contents from different organisms; known 3D structures of transporters, and phylogenetic trees of transporter families. On individual protein pages, users can find detailed functional annotation, supporting bioinformatic evidence, protein/DNA sequences, publications and cross-referenced external online resource links. TransportDB has now been in existence for over 10 years and continues to be regularly updated with new evidence and data from newly sequenced genomes, as well as having new features added periodically.

  19. Genetics and environmental regulation of Shigella iron transport systems.

    PubMed

    Wyckoff, Elizabeth E; Boulette, Megan L; Payne, Shelley M

    2009-02-01

    Shigella spp. have transport systems for both ferric and ferrous iron. The iron can be taken up as free iron or complexed to a variety of carriers. All Shigella species have both the Feo and Sit systems for acquisition of ferrous iron, and all have at least one siderophore-mediated system for transport of ferric iron. Several of the transport systems, including Sit, Iuc/IutA (aerobactin synthesis and transport), Fec (ferric di-citrate uptake), and Shu (heme transport) are encoded within pathogenicity islands. The presence and the genomic locations of these islands vary considerably among the Shigella species, and even between isolates of the same species. The expression of the iron transport systems is influenced by the concentration of iron and by environmental conditions including the level of oxygen. ArcA and FNR regulate iron transport gene expression as a function of oxygen tension, with the sit and iuc promoters being highly expressed in aerobic conditions, while the feo ferrous iron transporter promoter is most active under anaerobic conditions. The effects of oxygen are also seen in infection of cultured cells by Shigella flexneri; the Sit and Iuc systems support plaque formation under aerobic conditions, whereas Feo allows plaque formation anaerobically.

  20. Procurement of a fully licensed radioisotope thermoelectric generator transportation system

    SciTech Connect

    Adkins, H.E.; Bearden, T.E.

    1990-10-01

    A fully licensed transportation system for Radioisotope Thermoelectric Generators and Light-Weight Radioisotope Heater Units is currently being designed and built. The system will comply with all applicable US Department of Transportation regulations without the use of a DOE Alternative.'' The US Department of Transportation has special double containment'' requirements for plutonium. The system packaging uses a doubly contained bell jar'' concept. A refrigerated trailer is used for cooling the high-heat payloads. The same packaging is used for both high- and low-heat payloads. The system is scheduled to be available for use by mid-1992. 4 refs., 4 figs., 2 tabs.

  1. Procurement of a fully licensed radioisotope thermoelectric generator transportation system

    NASA Astrophysics Data System (ADS)

    Adkins, Harold E.; Bearden, Thomas E.

    1991-01-01

    A fully licensed transportation system for Radioisotope Thermoelectric Generators and Light-Weight Radioisotope Heater Units is currently being designed and built. The system will comply with all applicable U.S. Department of Transportation regulations without the use of a ``DOE Alternative.'' The U.S. Department of Transportation has special ``double containment'' requirements for plutonium. The system packaging uses a doubly contained ``bell jar'' concept. A refrigerated trailer is used for cooling the high-heat payloads. The same packaging is used for both high- and low-heat payloads. The system is scheduled to be available for use by mid-1992.

  2. Dynamic recruitment of amino acid transporters to the insect/symbiont interface.

    PubMed

    Duncan, Rebecca P; Husnik, Filip; Van Leuven, James T; Gilbert, Donald G; Dávalos, Liliana M; McCutcheon, John P; Wilson, Alex C C

    2014-03-01

    Symbiosis is well known to influence bacterial symbiont genome evolution and has recently been shown to shape eukaryotic host genomes. Intriguing patterns of host genome evolution, including remarkable numbers of gene duplications, have been observed in the pea aphid, a sap-feeding insect that relies on a bacterial endosymbiont for amino acid provisioning. Previously, we proposed that gene duplication has been important for the evolution of symbiosis based on aphid-specific gene duplication in amino acid transporters (AATs), with some paralogs highly expressed in the cells housing symbionts (bacteriocytes). Here, we use a comparative approach to test the role of gene duplication in enabling recruitment of AATs to bacteriocytes. Using genomic and transcriptomic data, we annotate AATs from sap-feeding and non sap-feeding insects and find that, like aphids, AAT gene families have undergone independent large-scale gene duplications in three of four additional sap-feeding insects. RNA-seq differential expression data indicate that, like aphids, the sap-feeding citrus mealybug possesses several lineage-specific bacteriocyte-enriched paralogs. Further, differential expression data combined with quantitative PCR support independent evolution of bacteriocyte enrichment in sap-feeding insect AATs. Although these data indicate that gene duplication is not necessary to initiate host/symbiont amino acid exchange, they support a role for gene duplication in enabling AATs to mediate novel host/symbiont interactions broadly in the sap-feeding suborder Sternorrhyncha. In combination with recent studies on other symbiotic systems, gene duplication is emerging as a general pattern in host genome evolution.

  3. Proton transport in triflic acid hydrates studied via path integral car-parrinello molecular dynamics.

    PubMed

    Hayes, Robin L; Paddison, Stephen J; Tuckerman, Mark E

    2009-12-31

    The mono-, di-, and tetrahydrates of trifluoromethanesulfonic acid, which contain characteristic H(3)O(+), H(5)O(2)(+), and H(9)O(4)(+) structures, provide model systems for understanding proton transport in materials with high perfluorosulfonic acid density such as perfluorosulfonic acid membranes commonly employed in hydrogen fuel cells. Ab initio molecular dynamics simulations indicate that protons in these solids are predisposed to transfer to the water most strongly bound to sulfonate groups via a Grotthuss-type mechanism, but quickly return to the most solvated defect structure either due to the lack of a nearby species to stabilize the new defect or a preference for the proton to be maximally hydrated. Path integral molecular dynamics of the mono- and dihydrate reveal significant quantum effects that facilitate proton transfer to the "presolvated" water or SO(3)(-) in the first solvation shell and increase the Zundel character of all the defects. These trends are quantified in free energy profiles for each bonding environment. Hydrogen bonding criteria for HOH-OH(2) and HOH-O(3)S are extracted from the two-dimensional potential of mean force. The quantum radial distribution function, radius of gyration, and root-mean-square displacement position correlation function show that the protonic charge is distributed over two or more water molecules. Metastable structural defects with one excess proton shared between two sulfonate groups and another Zundel or Eigen type cation defect are found for the mono- and dihydrate but not for the tetrahydrate crystal. Results for the tetrahydrate native crystal exhibit minor differences at 210 and 250 K. IR spectra are calculated for all native and stable defect structures. Graph theory techniques are used to characterize the chain lengths and ring sizes in the hydrogen bond network. Low conductivities when limited water is present may be attributable to trapping of protons between SO(3)(-) groups and the increased

  4. Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice

    PubMed Central

    Silvennoinen, Reija; Quesada, Helena; Kareinen, Ilona; Julve, Josep; Kaipiainen, Leena; Gylling, Helena; Blanco-Vaca, Francisco; Escola-Gil, Joan Carles; Kovanen, Petri T; Lee-Rueckert, Miriam

    2015-01-01

    Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage-specific reverse cholesterol transport, m-RCT) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid-treated animals, we investigated if chronic intermittent restraint stress would modify m-RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium-dependent bile acid transporter (ASBT), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m-RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage-derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m-RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m-RCT induction could have antiatherogenic potential under conditions of chronic stress. PMID:25969465

  5. Control of machine functions or transport systems

    SciTech Connect

    Woodley, M.D.; Lee, M.J.; Jaeger, J.; King, A.S.

    1983-01-01

    A computer code, COMFORT, has been developed at SLAC for on-line calculation of the strengths of magnetic elements in an electron storage ring or transport beam line, subject to first order fitting constraints on the ring or beam line parameters. This code can also be used off-line as an interactive lattice or beam line design tool.

  6. Intelligent transportation systems and intermodal freight transportation. Final report, May-December 1992

    SciTech Connect

    Aylward, A.D.

    1996-12-01

    This paper describes the various advanced technologies already in use in the intermodal freight transportation industry and addresses the opportunity for improved communication between the public and private sector regarding technology applications to the freight transportation system that could enhance the capacity of the system as a whole. The current public interest in freight transportation policy creates an opportunity to develop a shared vision of the future needs of international intermodal freight transportation in the United States. The Federal government can impact this vision by taking action in the following areas: Provide Infrastructure Funding to Support Efficiency and Global Competitiveness; Support Regional and Corridor Efforts; Understand the Freight Sector and Develop a Shared Vision of Technology Benefits; Lead Transportation Technology Efforts of Federal Agencies; and Maintain Commitment to Open ITS Architecture.

  7. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    PubMed

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease.

  8. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    PubMed

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. PMID:25616451

  9. Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2.

    PubMed

    Hosomi, Atsushi; Nakanishi, Takeo; Fujita, Takuya; Tamai, Ikumi

    2012-01-01

    Urinary excretion accounts for two-thirds of total elimination of uric acid and the remainder is excreted in feces. However, the mechanism of extra-renal elimination is poorly understood. In the present study, we aimed to clarify the mechanism and the extent of elimination of uric acid through liver and intestine using oxonate-treated rats and Caco-2 cells as a model of human intestinal epithelium. In oxonate-treated rats, significant amounts of externally administered and endogenous uric acid were recovered in the intestinal lumen, while biliary excretion was minimal. Accordingly, direct intestinal secretion was thought to be a substantial contributor to extra-renal elimination of uric acid. Since human efflux transporter BCRP/ABCG2 accepts uric acid as a substrate and genetic polymorphism causing a decrease of BCRP activity is known to be associated with hyperuricemia and gout, the contribution of rBcrp to intestinal secretion was examined. rBcrp was confirmed to transport uric acid in a membrane vesicle study, and intestinal regional differences of expression of rBcrp mRNA were well correlated with uric acid secretory activity into the intestinal lumen. Bcrp1 knockout mice exhibited significantly decreased intestinal secretion and an increased plasma concentration of uric acid. Furthermore, a Bcrp inhibitor, elacridar, caused a decrease of intestinal secretion of uric acid. In Caco-2 cells, uric acid showed a polarized flux from the basolateral to apical side, and this flux was almost abolished in the presence of elacridar. These results demonstrate that BCRP contributes at least in part to the intestinal excretion of uric acid as extra-renal elimination pathway in humans and rats.

  10. Transepithelial transport of aliphatic carboxylic acids studied in Madin Darby canine kidney (MDCK) cell monolayers.

    PubMed

    Cho, M J; Adson, A; Kezdy, F J

    1990-04-01

    Transport of 14C-labeled acetic, propionic (PA), butyric, valeric, heptanoic (HA), and octanoic (OA) acids across the Madin Darby canine kidney (MDCK) epithelial cell monolayer grown on a porous polycarbonate membrane was studied in Hanks' balanced salt solution (HBSS) at 37 degrees C in both apical-to-basolateral and basolateral-to-apical directions. At micromolar concentrations of solutes, metabolic decomposition was significant as evidenced by [14C]CO2 production during the OA transport. The apparent permeability (Pe) indicates that as lipophilicity increases, diffusion across the "unstirred" boundary layer becomes rate limiting. In support of this notion, transport of OA and HA was enhanced by agitation, showed an activation energy of 3.7 kcal/mol for OA, and resulted in identical Pe values for both transport directions. Analysis of Pe changes with varying alkyl chain length resulted in a delta G of -0.68 +/- 0.09 kcal/mol for -CH2-group transfer from an aqueous phase to the MDCK cells. When the intercellular tight junctions were opened by the divalent chelator EGTA in Ca2+/Mg2(+)-free HBSS, transport of the fluid-phase marker Lucifer yellow greatly increased because of paracellular leakage. PA transport also showed a significant increase, but OA transport was independent of EGTA. Although albumin also undergoes paracellular transport in the presence of EGTA and OA binds strongly to albumin, OA transport in EGTA solution was unchanged by albumin. These observations indicate that transmembrane transport is the major mechanism for lipophilic substances. The present study, together with earlier work on the transport of polar substances, shows that the MDCK cell monolayer is an excellent model of the transepithelial transport barrier.

  11. Transepithelial transport of aliphatic carboxylic acids studied in Madin Darby canine kidney (MDCK) cell monolayers

    SciTech Connect

    Cho, M.J.; Adson, A.; Kezdy, F.J. )

    1990-04-01

    Transport of 14C-labeled acetic, propionic (PA), butyric, valeric, heptanoic (HA), and octanoic (OA) acids across the Madin Darby canine kidney (MDCK) epithelial cell monolayer grown on a porous polycarbonate membrane was studied in Hanks' balanced salt solution (HBSS) at 37{degrees}C in both apical-to-basolateral and basolateral-to-apical directions. At micromolar concentrations of solutes, metabolic decomposition was significant as evidenced by (14C)CO2 production during the OA transport. The apparent permeability (Pe) indicates that as lipophilicity increases, diffusion across the unstirred boundary layer becomes rate limiting. In support of this notion, transport of OA and HA was enhanced by agitation, showed an activation energy of 3.7 kcal/mol for OA, and resulted in identical Pe values for both transport directions. Analysis of Pe changes with varying alkyl chain length resulted in a delta G of -0.68 +/- 0.09 kcal/mol for -CH2-group transfer from an aqueous phase to the MDCK cells. When the intercellular tight junctions were opened by the divalent chelator EGTA in Ca2+/Mg2(+)-free HBSS, transport of the fluid-phase marker Lucifer yellow greatly increased because of paracellular leakage. PA transport also showed a significant increase, but OA transport was independent of EGTA. Although albumin also undergoes paracellular transport in the presence of EGTA and OA binds strongly to albumin, OA transport in EGTA solution was unchanged by albumin. These observations indicate that transmembrane transport is the major mechanism for lipophilic substances. The present study, together with earlier work on the transport of polar substances, shows that the MDCK cell monolayer is an excellent model of the transepithelial transport barrier.

  12. A 10-Gbps optical WiMAX transport system.

    PubMed

    Lin, Ying-Pyng; Lu, Hai-Han; Wu, Po-Yi; Chen, Chia-Yi; Jhang, Tai-Wei; Ruan, Sheng-Siang; Wu, Kuan-Hung

    2014-02-10

    A 10-Gbps optical worldwide interoperability for microwave access (WiMAX) transport system employing vertical cavity surface emitting laser (VCSEL) and spatial light modulator (SLM) with 16-quadrature amplitude modulation (QAM)-orthogonal frequency-division multiplexing (OFDM) modulating signal is proposed. With the assistance of equalizer and low noise amplifier (LNA) at the receiving site, good bit error rate (BER) performance, clear constellation map, and clear eye diagram are achieved in the proposed systems. An optical WiMAX transport system, transmitting 16-QAM-OFDM signal over a 6-m free-space link, with a data rate of 10 Gbps is successfully demonstrated. Such a 10-Gbps optical WiMAX transport system would be attractive for providing services including Internet and telecommunication services. Our proposed system is suitable for the free-space lightwave transport system in visible light communication (VLC) application. PMID:24663567

  13. A 10-Gbps optical WiMAX transport system.

    PubMed

    Lin, Ying-Pyng; Lu, Hai-Han; Wu, Po-Yi; Chen, Chia-Yi; Jhang, Tai-Wei; Ruan, Sheng-Siang; Wu, Kuan-Hung

    2014-02-10

    A 10-Gbps optical worldwide interoperability for microwave access (WiMAX) transport system employing vertical cavity surface emitting laser (VCSEL) and spatial light modulator (SLM) with 16-quadrature amplitude modulation (QAM)-orthogonal frequency-division multiplexing (OFDM) modulating signal is proposed. With the assistance of equalizer and low noise amplifier (LNA) at the receiving site, good bit error rate (BER) performance, clear constellation map, and clear eye diagram are achieved in the proposed systems. An optical WiMAX transport system, transmitting 16-QAM-OFDM signal over a 6-m free-space link, with a data rate of 10 Gbps is successfully demonstrated. Such a 10-Gbps optical WiMAX transport system would be attractive for providing services including Internet and telecommunication services. Our proposed system is suitable for the free-space lightwave transport system in visible light communication (VLC) application.

  14. Substrate-specific effects of pirinixic acid derivatives on ABCB1-mediated drug transport

    PubMed Central

    Michaelis, Martin; Rothweiler, Florian; Wurglics, Mario; Aniceto, Natália; Dittrich, Michaela; Zettl, Heiko; Wiese, Michael; Wass, Mark; Ghafourian, Taravat; Schubert-Zsilavecz, Manfred; Cinatl, Jindrich

    2016-01-01

    Pirinixic acid derivatives, a new class of drug candidates for a range of diseases, interfere with targets including PPARα, PPARγ, 5-lipoxygenase (5-LO), and microsomal prostaglandin and E2 synthase-1 (mPGES1). Since 5-LO, mPGES1, PPARα, and PPARγ represent potential anti-cancer drug targets, we here investigated the effects of 39 pirinixic acid derivatives on prostate cancer (PC-3) and neuroblastoma (UKF-NB-3) cell viability and, subsequently, the effects of selected compounds on drug-resistant neuroblastoma cells. Few compounds affected cancer cell viability in low micromolar concentrations but there was no correlation between the anti-cancer effects and the effects on 5-LO, mPGES1, PPARα, or PPARγ. Most strikingly, pirinixic acid derivatives interfered with drug transport by the ATP-binding cassette (ABC) transporter ABCB1 in a drug-specific fashion. LP117, the compound that exerted the strongest effect on ABCB1, interfered in the investigated concentrations of up to 2μM with the ABCB1-mediated transport of vincristine, vinorelbine, actinomycin D, paclitaxel, and calcein-AM but not of doxorubicin, rhodamine 123, or JC-1. In silico docking studies identified differences in the interaction profiles of the investigated ABCB1 substrates with the known ABCB1 binding sites that may explain the substrate-specific effects of LP117. Thus, pirinixic acid derivatives may offer potential as drug-specific modulators of ABCB1-mediated drug transport. PMID:26887049

  15. Normal and impaired charge transport in biological systems

    NASA Astrophysics Data System (ADS)

    Miller, John H.; Villagrán, Martha Y. Suárez; Maric, Sladjana; Briggs, James M.

    2015-03-01

    We examine the physics behind some of the causes (e.g., hole migration and localization that cause incorrect base pairing in DNA) and effects (due to amino acid replacements affecting mitochondrial charge transport) of disease-implicated point mutations, with emphasis on mutations affecting mitochondrial DNA (mtDNA). First we discuss hole transport and localization in DNA, including some of our quantum mechanical modeling results, as they relate to certain mutations in cancer. Next, we give an overview of electron and proton transport in the mitochondrial electron transport chain, and how such transport can become impaired by mutations implicated in neurodegenerative diseases, cancer, and other major illnesses. In particular, we report on our molecular dynamics (MD) studies of a leucine→arginine amino acid replacement in ATP synthase, encoded by the T→G point mutation at locus 8993 of mtDNA. This mutation causes Leigh syndrome, a devastating maternally inherited neuromuscular disorder, and has been found to trigger rapid tumor growth in prostate cancer cell lines. Our MD results suggest, for the first time, that this mutation adversely affects water channels that transport protons to and from the c-ring of the rotary motor ATP synthase, thus impairing the ability of the motor to produce ATP. Finally, we discuss possible future research topics for biological physics, such as mitochondrial complex I, a large proton-pumping machine whose physics remains poorly understood.

  16. Nuclear reactor heat transport system component low friction support system

    DOEpatents

    Wade, Elman E.

    1980-01-01

    A support column for a heavy component of a liquid metal fast breeder reactor heat transport system which will deflect when the pipes leading coolant to and from the heavy component expand or contract due to temperature changes includes a vertically disposed pipe, the pipe being connected to the heavy component by two longitudinally spaced cycloidal dovetail joints wherein the distal end of each of the dovetails constitutes a part of the surface of a large diameter cylinder and the centerlines of these large diameter cylinders intersect at right angles and the pipe being supported through two longitudinally spaced cycloidal dovetail joints wherein the distal end of each of the dovetails constitutes a part of the surface of a large diameter cylinder and the centerlines of these large diameter cylinders intersect at right angles, each of the cylindrical surfaces bearing on a flat and horizontal surface.

  17. Human behavior research and the design of sustainable transport systems

    NASA Astrophysics Data System (ADS)

    Schauer, James J.

    2011-09-01

    Transport currently represents approximately 19% of the global energy demand and accounts for about 23% of the global carbon dioxide emissions (IEA 2009). As the demand for mobility is expected to continue to increase in the coming decades, the stabilization of atmospheric carbon dioxide levels will require the evolution of transport, along with power generation, building design and manufacturing. The continued development of these sectors will need to include changes in energy sources, energy delivery, materials, infrastructure and human behavior. Pathways to reducing carbon from the transport sector have unique challenges and opportunities that are inherent to the human choices and behavioral patterns that mold the transportation systems and the associated energy needs. Technology, government investment, and regulatory policies have a significant impact on the formulation of transportation infrastructure; however, the role of human behavior and public acceptance on the efficiency and effectiveness of transport systems should not be underestimated. Although developed, rapidly developing, and underdeveloped nations face different challenges in the establishment of transport infrastructure that can meet transport needs while achieving sustainable carbon dioxide emissions, the constraints that establish the domain of possibilities are closely related for all nations. These constraints include capital investment, fuel supplies, power systems, and human behavior. Throughout the world, there are considerable efforts directed at advancing and optimizing the financing of sustainable infrastructures, the production of low carbon fuels, and the production of advanced power systems, but the foundational work on methods to understand human preferences and behavior within the context of transport and the valuation of reductions in carbon dioxide emissions is greatly lagging behind. These methods and the associated understanding of human behavior and the willingness to pay for

  18. Electrical Power Systems for NASA's Space Transportation Program

    NASA Technical Reports Server (NTRS)

    Lollar, Louis F.; Maus, Louis C.

    1998-01-01

    Marshall Space Flight Center (MSFC) is the National Aeronautics and Space Administration's (NASA) lead center for space transportation systems development. These systems include earth to orbit launch vehicles, as well as vehicles for orbital transfer and deep space missions. The tasks for these systems include research, technology maturation, design, development, and integration of space transportation and propulsion systems. One of the key elements in any transportation system is the electrical power system (EPS). Every transportation system has to have some form of electrical power and the EPS for each of these systems tends to be as varied and unique as the missions they are supporting. The Preliminary Design Office (PD) at MSFC is tasked to perform feasibility analyses and preliminary design studies for new projects, particularly in the space transportation systems area. All major subsystems, including electrical power, are included in each of these studies. Three example systems being evaluated in PD at this time are the Liquid Fly Back Booster (LFBB) system, the Human Mission to Mars (HMM) study, and a tether based flight experiment called the Propulsive Small Expendable Deployer System (ProSEDS). These three systems are in various stages of definition in the study phase.

  19. Disposition and transportation of surplus radioactive low specific activity nitric acid. Volume 1, Environmental Assessment

    SciTech Connect

    1995-05-01

    DOE is deactivating the PUREX plant at Hanford; this will involve the disposition of about 692,000 liters (183,000 gallons) of surplus nitric acid contaminated with low levels of U and other radionuclides. The nitric acid, designated as low specific activity, is stored in 4 storage tanks at PUREX. Five principal alternatives were evaluated: transfer for reuse (sale to BNF plc), no action, continued storage in Hanford upgraded or new facility, consolidation of DOE surplus acid, and processing the LSA nitric acid as waste. The transfer to BNF plc is the preferred alternative. From the analysis, it is concluded that the proposed disposition and transportation of the acid does not constitute a major federal action significantly affecting the quality of the human environment within the meaning of NEPA; therefore an environmental impact statement is not required.

  20. Transport of sodium across the isolated bovine rumen epithelium: interaction with short-chain fatty acids, chloride and bicarbonate.

    PubMed

    Sehested, J; Diernaes, L; Moller, P D; Skadhauge, E

    1996-01-01

    Unidirectional transport rates of sodium (22Na+) and chloride (36Cl-) across bovine rumen epithelium were measured in vitro by the Ussing chamber technique. The active and short-chain fatty acid (SCFA)-stimulated sodium transport was shown to fit Michaelis-Menten kinetics, and was rate limited mainly by one transport system, characterized by a Km of 43 mmol l-1 Na+ and a Jmax (maximal transport rate) of 6.2 mumol cm-2 h-1 Na+. It was confirmed that the basolateral Na+,K(+)-ATPase was essential for active sodium transport, and that an apical amiloride-sensitive sodium transport system (Na(+)-H+ exchange) was involved in a minimum of 60-70% of the active sodium transport in the presence of SCFAs (butyrate). The main part of both the mucosal-serosal (MS) and serosal-mucosal (SM) sodium flux was sensitive to an applied electrical potential difference (PD). It is noteworthy that an applied PD, equal to the in vivo PD (+30 mV, lumen as reference), abolished net transport of sodium. The stimulating effect of a mixture of acetate, propionate and butyrate on active sodium transport was confirmed, and it was further shown that the stimulating effect of each of the three SCFAs was nearly equal. Analogues of naturally occurring SCFAs (isobutyrate and 2-ethyl-butyrate) did not stimulate active sodium transport, but inhibited the stimulating effect of butyrate. The stimulating effect of butyrate was clearly concentration dependent and showed a maximum at approximately 20 mmol l-1 butyrate. Above this limit active sodium transport was decreased with increasing butyrate concentration. This suggests that there was a limit to the amount of butyrate that could be handled by the epithelium. The active sodium transport was clearly correlated with the chloride concentration, and was significantly reduced, but not abolished, by replacement of chloride with gluconate. Active transport of chloride was stimulated by butyrate and reduced by the Na(+)-H+ exchange inhibitor amiloride (3 mmol l

  1. Natural hazard impacts on transport systems: analyzing the data base of transport accidents in Russia

    NASA Astrophysics Data System (ADS)

    Petrova, Elena

    2015-04-01

    We consider a transport accident as any accident that occurs during transportation of people and goods. It comprises of accidents involving air, road, rail, water, and pipeline transport. With over 1.2 million people killed each year, road accidents are one of the world's leading causes of death; another 20-50 million people are injured each year on the world's roads while walking, cycling, or driving. Transport accidents of other types including air, rail, and water transport accidents are not as numerous as road crashes, but the relative risk of each accident is much higher because of the higher number of people killed and injured per accident. Pipeline ruptures cause large damages to the environment. That is why safety and security are of primary concern for any transport system. The transport system of the Russian Federation (RF) is one of the most extensive in the world. It includes 1,283,000 km of public roads, more than 600,000 km of airlines, more than 200,000 km of gas, oil, and product pipelines, 115,000 km of inland waterways, and 87,000 km of railways. The transport system, especially the transport infrastructure of the country is exposed to impacts of various natural hazards and weather extremes such as heavy rains, snowfalls, snowdrifts, floods, earthquakes, volcanic eruptions, landslides, snow avalanches, debris flows, rock falls, fog or icing roads, and other natural factors that additionally trigger many accidents. In June 2014, the Ministry of Transport of the RF has compiled a new version of the Transport Strategy of the RF up to 2030. Among of the key pillars of the Strategy are to increase the safety of the transport system and to reduce negative environmental impacts. Using the data base of technological accidents that was created by the author, the study investigates temporal variations and regional differences of the transport accidents' risk within the Russian federal regions and a contribution of natural factors to occurrences of different

  2. Nucleocytoplasmic transport of ribosomes in a eukaryotic system: Is there a facilitated transport process

    SciTech Connect

    Khanna-Gupta, A.; Ware, V.C. )

    1989-03-01

    The authors have examined the kinetics of the process by which ribosomes are exported from the nucleus to the cytoplasm using Xenopus laevis oocytes microinjected into the germinal vesicle with radiolabeled ribosomes or ribosomal subunits from X. laevis, Tetrahymena thermophila, or Escherichia coli. Microinjected eukaryotic mature ribosomes are redistributed into the oocyte cytoplasm by an apparent carrier-mediated transport process that exhibits saturation kinetics as increasing amounts of ribosomes are injected. T. thermophila ribosomes are competent to traverse the Xenopus nuclear envelope, suggesting that the basic mechanism underlying ribosome transport is evolutionarily conserved. Microinjected E. coli ribosomes are not transported in this system, indicating that prokaryotic ribosomes lack the signals required for transport. Surprisingly, coinjected small (40S) and large (60S) subunits from T. thermophila are transported significantly faster than individual subunits. These observations support a facilitated transport model for the translocation of ribosomal subunits as separate units across the nuclear envelope whereby the transport rate of 60S or 40S subunits is enhanced by the presence of the partner subunit. Although the basic features of the transport mechanism have been preserved through evolution, other aspects of the process may be mediated through species-specific interactions. They hypothesize that a species-specific nuclear 40S-60S subunit association may expedite the transport of individual subunits across the nuclear envelope.

  3. Cellular distribution of the neutral amino acid transporter subtype ASCT2 in mouse brain.

    PubMed

    Gliddon, Catherine M; Shao, Zongjun; LeMaistre, Jillian L; Anderson, Christopher M

    2009-01-01

    ASCT2 is an ASC (alanine-, serine-, cysteine-preferring) neutral amino acid exchanger that may regulate CNS function by transporting amino acid substrates including L-serine, L-cysteine, L-glutamine, L-glutamate and D-serine. Despite the potentially important role of ASCT2 in influencing metabolic and signaling functions of these amino acids in brain, there has been little description of its distribution in brain tissue. We employed a commercially available human ASCT2 antibody in immunohistochemistry studies in adult mouse brain and found a wide regional distribution for ASCT2 that was limited to dendrites labeled by anti-microtubule-associated protein-2 in cortex, hippocampus and striatum. No ASCT2 immunoreactivity was observed in areas labeled by antibodies against a neuronal cell body marker (NeuN), or either of the astrocyte markers, glial fibrillary acidic protein or S100beta. In cerebellum both Purkinje cell bodies and dendrites were positive for ASCT2 immunoreactivity. In support of a dendritic localization for ASCT2 in cortex, low affinity (K(T) > 1 mM), Na(+)-dependent D-serine and L-glutamine uptake characteristic of ASCT2-mediated transport was observed in P2 synaptosomal preparations. These results suggest that ASCT2 may be an important neuronal neutral amino acid transporter and highlight a discrepancy between findings of astrocyte ASCT2 function in tissue culture and brain in situ.

  4. Intracellular pH regulation by acid-base transporters in mammalian neurons

    PubMed Central

    Ruffin, Vernon A.; Salameh, Ahlam I.; Boron, Walter F.; Parker, Mark D.

    2014-01-01

    Intracellular pH (pHi) regulation in the brain is important in both physiological and physiopathological conditions because changes in pHi generally result in altered neuronal excitability. In this review, we will cover 4 major areas: (1) The effect of pHi on cellular processes in the brain, including channel activity and neuronal excitability. (2) pHi homeostasis and how it is determined by the balance between rates of acid loading (JL) and extrusion (JE). The balance between JE and JL determine steady-state pHi, as well as the ability of the cell to defend pHi in the face of extracellular acid-base disturbances (e.g., metabolic acidosis). (3) The properties and importance of members of the SLC4 and SLC9 families of acid-base transporters expressed in the brain that contribute to JL (namely the Cl-HCO3 exchanger AE3) and JE (the Na-H exchangers NHE1, NHE3, and NHE5 as well as the Na+- coupled HCO3− transporters NBCe1, NBCn1, NDCBE, and NBCn2). (4) The effect of acid-base disturbances on neuronal function and the roles of acid-base transporters in defending neuronal pHi under physiopathologic conditions. PMID:24592239

  5. Reconstitution of bile acid transport in the rat hepatoma McArdle RH-7777 cell line.

    PubMed

    Torchia, E C; Shapiro, R J; Agellon, L B

    1996-07-01

    The liver recovers bile acids from the portal circulation primarily via an active process that is dependent on sodium ions. Hepatocytes lose the ability to transport bile acids in culture, and, in liver-derived permanent cell lines, this ability is severely reduced or absent. To study the importance of bile acids in regulating liver-specific functions (e.g., cellular bile acid and cholesterol metabolism), we have re-established active bile acid transport in cultured cells. The complementary DNA (cDNA) encoding the rat sodium/taurocholate cotransporting polypeptide (ntcp) was placed under the control of a cytomegalovirus promoter and transfected into the rat hepatoma cell line, McArdle RH-7777. Transfected cells were screened for the ability to take up [3H]-taurocholate. Clones that displayed the ability to take up taurocholate were expanded (designated McNtcp) and further characterized. The apparent Michaelis constant (Km) for taurocholate uptake was similar among the different clones. The observed maximum velocity (Vmax), however, differed and was positively correlated with the abundance of recombinant ntcp messenger RNA (mRNA). The highest level of taurocholate uptake activity observed in McNtcp cells was comparable with that of freshly isolated hepatocytes. Efflux of accumulated taurocholate from McNtcp cells proceeded in a manner similar to primary hepatocytes, indicating that McArdle RH-7777 cells have retained the ability to secrete bile acids. Moreover, taurocholate uptake in McNtcp cells was inhibited by other bile acid species. Based on the observed kinetic parameters, the reconstituted McArdle RH-7777 cells mimic the ability of primary hepatocytes to transport bile acids.

  6. Dietary regulation of intestinal brush-border sugar and amino acid transport in carnivores.

    PubMed

    Buddington, R K; Chen, J W; Diamond, J M

    1991-10-01

    The ability of omnivores and herbivores to regulate reversibly their intestinal brush-border nutrient transporters is functionally related to the unpredictably variable composition of their natural diets. To determine whether carnivores are able similarly to regulate the activities of their intestinal nutrient transporters, we fed to three species of vertebrates that are carnivorous as adults (cats, mink, and leopard frogs) diets with either at least 50% digestible carbohydrate or with negligible carbohydrate levels. Rates of transport for the sugars glucose and fructose and the amino acids (AAs) aspartate, leucine, lysine, and proline were measured throughout the intestine (only proline and glucose in the frogs) by an in vitro everted-sleeve method. Although all three species consume much carbohydrate during early development, only the mink was able to regulate sugar transporter activity in response to changes in levels of dietary carbohydrate. In contrast, the sugar transporters of the cat were unresponsive to varying carbohydrate levels, and long-term feeding of a high-carbohydrate diet caused down-regulation of sugar transport in frogs. Of the three species, only the mink is a member of a family that includes omnivorous species, whereas all members of the families to which the cat and frog belong are carnivorous as adults. All three species were able to regulate rates of AA transport, though the patterns and magnitude of the responses differed between species as well as between AAs, suggesting independent regulation of some AA transporters.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Crawler Transporter Steering and Jel Systems

    NASA Technical Reports Server (NTRS)

    Davis, V. L.

    1975-01-01

    The transporter weighing 2.8 million kilograms (6.3 million pounds) was used to lift a 5.7-million-kilogram (12.6-million-pound) combination of mobile launcher and space vehicle, transfer this load approximately 5.6 kilometers (3.5 miles) from its point of assembly, negotiate curves of 152-meter (500-foot) mean radius, climb a 5-percent grade while maintaining the 122-meter (400-foot) structure in a vertical position within 10 minutes of arc, and smoothly position this huge structure to within plus or minus 5.1 centimeters (plus or minus 2 inches) on support pedestals at the launch pad. The crawler-transporter is described in detail.

  8. Molecular modeling of proton transport in the short-side-chain perfluorosulfonic acid ionomer.

    PubMed

    Hristov, Iordan H; Paddison, Stephen J; Paul, Reginald

    2008-03-13

    An explanation for the superior proton conductivity of low equivalent weight (EW) short-side-chain (SSC) perfluorosulfonic acid membranes is pursued through the determination of hydrated morphology and hydronium ion diffusion coefficients using classical molecular dynamics (MD) simulations. A unique force field set for the SSC ionomer was derived from torsion profiles determined from ab initio electronic structure calculations of an oligomeric fragment consisting of two side chains. MD simulations were performed on a system consisting of a single macromolecule of the polymer (EW of 580) with the general formula F3C-[CF(OCF2CF2SO3H)-(CF2)7]40-CF3 at hydration levels corresponding to 3, 6, and 13 water molecules per sulfonic acid group. Examination of the hydrated morphology indicates the formation of hydrogen bond "bridges" between distant sulfonate groups without significant bending of the polytetrafluoroethylene backbone. Pair correlation functions of the system identify the presence of ion cages consisting of hydronium ions hydrogen-bonded to three sulfonate groups at the lowest water content. Such structures exhibit very low S-OH3+ separations, well below 4 A and severely inhibit vehicular diffusion of the protons. The number of sulfonate groups in the first solvation shell of a given hydronium ion correlates well with the differences between Nafion and the SSC polymer (Hyflon). The calculated hydronium ion diffusion coefficients of 2.84 x 10-7, 1.36 x 10-6, and 3.47 x 10-6 cm2/s for water contents of 3, 6, and 13, respectively, show only good agreement to experimentally measured values at the lowest water content, underscoring the increasing contribution of proton shuttling or hopping at the higher hydration levels. At the highest water content, the vehicular diffusion accounts for only about 1/5 of the total proton transport similar to that observed in Nafion. PMID:18281980

  9. Glucocorticoid regulation of amino acid transport in anucleate rat hepatoma (HTC) cells

    PubMed Central

    1981-01-01

    The transport of alpha-aminoisobutyric acid (AIB) by rat hepatoma tissue culture (HTC) cells is rapidly and reversibly inhibited by dexamethasone and other glucocorticoids. To investigate the role of the nucleus in the regulation of transport and to determine whether steroid hormones or steroid-receptor complexes may have direct effects on cytoplasmic or membrane functions, we have examined the regulation of transport by dexamethasone in anucleate HTC cells. Cytoplasts prepared from suspension cultures of HTC cells fully retain active transport of AIB with the same kinetic properties as intact cells. However, the uptake of AIB is not inhibited by dexamethasone or other corticosteroids. Neither is the inhibited rate of transport, manifested by cytoplasts prepared from dexamethasone-treated cells, restored to normal upon removal of the hormone. Anucleate cells exhibit specific, saturable binding of [3H]dexamethasone; however, the binding is reduced compared with that of intact cells. The nucleus is thus required for the glucocorticoid regulation of amino acid transport in HTC cells. PMID:7217203

  10. Modulating Effect of Ascorbic Acid on Transport-Induced Immunosuppression in Goats

    PubMed Central

    Minka, Ndazo Salka; Ayo, Joseph Olusegun

    2011-01-01

    The effect of 12 h road transportation on some basic blood cells and the modulating role of ascorbic acid were investigated in 40 adult Red Sokoto goats during the hot dry season. The animals were divided into two groups, GI (experimental; n = 20) and GII (control; n = 20). Group 1 was administered with ascorbic acid (AA) per os at a dosage rate of 100 mg/kg body weight, while GII was given 10 mL of sterile water per goat. Forty minutes after the administration and loading, the goats were transported for 12 h. The result obtained in GII goats showed that loading, transportation, high ambient temperature (AT), and relative humidity (RH) encountered during transportation induced lymphopenia, neutrophilia, and eosinopenia, which can cause immunosuppression. In GI goats, the administration of AA prior to loading and transportation ameliorated the adverse effects of loading and transportation stress on neutrophil/lymphocyte ratio and eosinopenia of the goats. PMID:23738106

  11. Heating and Cooling System Design for a Modern Transportable Container

    SciTech Connect

    Berger, Jason E.

    2015-06-01

    Sandia National Laboratories (SNL) has been tasked with the design of a modern transportable container (MTC) for use in high reliability transportation environments. The container is required to transport cargo capable of generating its own heat and operate under the United States’ climatic extremes. In response to these requirements, active heating and cooling is necessary to maintain a controlled environment inside the container. The following thesis project documents the design of an active heating, active cooling, and combined active heating and cooling system (now referred to as active heating and cooling systems) through computational thermal analyses, scoping of commercial system options, and mechanical integration with the container’s structure.

  12. Use of MPEG transport stream in TV systems

    NASA Astrophysics Data System (ADS)

    Narasimhan, Sam

    1995-12-01

    This tutorial contribution covers the use of International Standard IS 13818-1 (MPEG-2 Systems) Transport Stream in Digital TV systems with main emphasis on broadcast systems. The Transport stream was developed by Working Group II of ISO/IEC JTC1 as a means for multiplexing and synchronizing multiple video and audio data as well as for transmission in a non-error resilient environment. This paper describes some salient features of the Transport Stream and details of how it is used to implement a complete end to end digital TV broadcast service with examples of functionality to support data, channel acquisition, navigation and near video on demand services.

  13. Role of sodium ion in transport of folic acid in the small intestine

    SciTech Connect

    Zimmerman, J.; Selhub, J.; Rosenberg, I.H.

    1986-08-01

    The effect of sodium on folate transport across the intestinal luminal membrane was analyzed using two techniques: the influx chamber and isoalted brush-border membrane vesicles. Preincubation of tissue in Na -free medium did not have a consistent effect on folic acid influx provided that Na was present in the test solution. Replacement of Na in the test solution by choline resulted in a significant reduction of folic acid influx. However, when intestinal sheets that had been equilibrated in Na -free solution were exposed to test solutions containing either Na , Li , K , Rb , Cs , Tris , or guanidinium as main cations, folic acid influx was not significantly decreased. Concentration-dependence studies showed that replacement of Na by Rb did not affect the saturable mechanism of folate transport. Rather, a decrease in nonsaturable folic acid uptake accounted for the slightly reduced influx observed in the presence of Rb . Experiments with brush-border membrane vesicles revealed that methotrexate uptake was significantly higher in the presence of external Na than in the presence of K , but was not different from uptake in the presence of K plus valinomycin. These data suggest that 1) the saturable component of folate transport is not Na dependent, and 2) nonsaturable transport of folic acid across the luminal membrane occurs in part through a conductive pathway that involves a negatively charged species of folate and a cation whose membrane permeability affects the rate of folate transport. The importance of Na in this process in vivo derives from the fact that Na is the most permeant cation available at the absorptive site in the small intestine.

  14. A Numbering System for MFS Transporter Proteins

    PubMed Central

    Lee, Joanna; Sands, Zara A.; Biggin, Philip C.

    2016-01-01

    The Major Facilitator Superfamily (MFS) is one of the largest classes of secondary active transporters and is widely expressed in many domains of life. It is characterized by a common 12-transmembrane helix motif that allows the selective transport of a vast range of diverse substrates across the membrane. MFS transporters play a central role in many physiological processes and are increasingly recognized as potential drug targets. Despite intensive efforts, there are still only a handful of crystal structures and therefore homology modeling is likely to be a necessary process for providing models to interpret experiments for many years to come. However, the diversity of sequences and the multiple conformational states these proteins can exist in makes the process significantly more complicated, especially for sequences for which there is very little sequence identity to known templates. Inspired by the approach adopted many years ago for GPCRs, we have analyzed the large number of MFS sequences now available alongside the current structural information to propose a series of conserved contact points that can provide additional guidance for the homology modeling process. To enable cross-comparison across MFS models we also present a numbering scheme that can be used to provide a point of reference within each of the 12 transmembrane regions. PMID:27314000

  15. Inhibition of ileal bile acid transporter: An emerging therapeutic strategy for chronic idiopathic constipation

    PubMed Central

    Mosińska, Paula; Fichna, Jakub; Storr, Martin

    2015-01-01

    Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation-associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipation-related symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation. PMID:26139989

  16. Inhibition of ileal bile acid transporter: An emerging therapeutic strategy for chronic idiopathic constipation.

    PubMed

    Mosińska, Paula; Fichna, Jakub; Storr, Martin

    2015-06-28

    Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation-associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipation-related symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation. PMID:26139989

  17. Systems evaluation of low density air transportation concepts

    NASA Technical Reports Server (NTRS)

    Bruce, R. W.; Webb, H. M.

    1972-01-01

    Methods were studied for improving air transportation to low-density population regions in the U.S. through the application of new aeronautical technology. The low-density air service concepts are developed for selected regions, and critical technologies that presently limit the effective application of low-density air transportation systems are identified.

  18. Automated transportation management system (ATMS) software project management plan (SPMP)

    SciTech Connect

    Weidert, R.S., Westinghouse Hanford

    1996-05-20

    The Automated Transportation Management System (ATMS) Software Project Management plan (SPMP) is the lead planning document governing the life cycle of the ATMS and its integration into the Transportation Information Network (TIN). This SPMP defines the project tasks, deliverables, and high level schedules involved in developing the client/server ATMS software.

  19. Conceptual design of an RTG Facility Transportation System

    SciTech Connect

    Black, S.J.; Gentzlinger, R.C.; Lujan, R.E.

    1994-06-03

    The conceptual design of an Radioisotope Thermoelectric Generator (RTG) Facility Transportation System which is part of the overall RTG Transportation System has been completed and is described in detail. The Facility Transportation System serves to provide locomotion, cooling, shock protection and data acquisition for the RTG package during loading and unloading sequences. The RTG Facility Transportation System consists of a Transporter Subsystem, a Package Cooling Subsystem, and a Shock Limiting Transit Device Subsystem. The Transporter Subsystem is a uniquely designed welded steel cart combined with a pneumatically-driven hand tug for locomotion. The Package Cooling Subsystem provides five