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Sample records for ph modulates transport

  1. pH modulation of glial glutamate transporters regulates synaptic transmission in the nucleus of the solitary tract

    Science.gov (United States)

    McCrimmon, Donald R.; Martina, Marco

    2013-01-01

    The nucleus of the solitary tract (NTS) is the major site for termination of visceral sensory afferents contributing to homeostatic regulation of, for example, arterial pressure, gastric motility, and breathing. Whereas much is known about how different neuronal populations influence these functions, information about the role of glia remains scant. In this article, we propose that glia may contribute to NTS functions by modulating excitatory neurotransmission. We found that acidification (pH 7.0) depolarizes NTS glia by inhibiting K+-selective membrane currents. NTS glia also showed functional expression of voltage-sensitive glutamate transporters, suggesting that extracellular acidification regulates synaptic transmission by compromising glial glutamate uptake. To test this hypothesis, we evoked glutamatergic slow excitatory potentials (SEPs) in NTS neurons with repetitive stimulation (20 pulses at 10 Hz) of the solitary tract. This SEP depends on accumulation of glutamate following repetitive stimulation, since it was potentiated by blocking glutamate uptake with dl-threo-β-benzyloxyaspartic acid (TBOA) or a glia-specific glutamate transport blocker, dihydrokainate (DHK). Importantly, extracellular acidification (pH 7.0) also potentiated the SEP. This effect appeared to be mediated through a depolarization-induced inhibition of glial transporter activity, because it was occluded by TBOA and DHK. In agreement, pH 7.0 did not directly alter d-aspartate-induced responses in NTS glia or properties of presynaptic glutamate release. Thus acidification-dependent regulation of glial function affects synaptic transmission within the NTS. These results suggest that glia play a modulatory role in the NTS by integrating local tissue signals (such as pH) with synaptic inputs from peripheral afferents. PMID:23615553

  2. pH modulates transport rates of manganese and cadmium in the green alga Chlamydomonas reinhardtii through non-competitive interactions: Implications for an algal BLM

    International Nuclear Information System (INIS)

    Francois, Laura; Fortin, Claude; Campbell, Peter G.C.

    2007-01-01

    The influence of pH on short-term uptake of manganese and cadmium by the green alga Chlamydomonas reinhardtii was studied to better understand the nature of proton interactions with metal membrane transporters. Manganese and cadmium internalization fluxes (J int ) were measured over a wide range of free metal ion concentrations from 1 x 10 -10 to 4 x 10 -4 M at several pH values (Mn: 5.0, 6.5 and 8.0; Cd: 5.0 and 6.5). For both metals, first-order biological internalization kinetics were observed but the maximum transport flux (J max ) decreased when pH decreased, in contradiction with the Biotic Ligand Model (BLM). This result suggested a non-competitive inhibition of metal uptake by the H + -ion. A Michaelis-Menten type inhibition model considering proton and calcium competition was tested. The metal biotic ligand stability constants and the stability constants for competitive binding of Ca 2+ and H + with the metal transporters were calculated: for manganese, K Mn = 10 4.20 and K Ca = 10 3.71 ; for cadmium, K Cd = 10 4.19 and K Ca = 10 4.76 ; for both metal transport systems, K H was not a significant parameter. Furthermore, metal uptake was not significantly influenced by the pH of the antecedent growth medium, suggesting that increases in metal fluxes as the pH is raised are caused by conformational changes of the surface transport proteins rather than by the synthesis of additional transport sites. Our results demonstrate that the BLM in its present state does not properly describe the true influence of pH on manganese and cadmium uptake by algae and that a non-competitive inhibition component must be integrated

  3. Oxygen limitation modulates pH regulation of catabolism and hydrogenases, multidrug transporters, and envelope composition in Escherichia coli K-12

    Directory of Open Access Journals (Sweden)

    Radmacher Michael D

    2006-10-01

    Full Text Available Abstract Background In Escherichia coli, pH regulates genes for amino-acid and sugar catabolism, electron transport, oxidative stress, periplasmic and envelope proteins. Many pH-dependent genes are co-regulated by anaerobiosis, but the overall intersection of pH stress and oxygen limitation has not been investigated. Results The pH dependence of gene expression was analyzed in oxygen-limited cultures of E. coli K-12 strain W3110. E. coli K-12 strain W3110 was cultured in closed tubes containing LBK broth buffered at pH 5.7, pH 7.0, and pH 8.5. Affymetrix array hybridization revealed pH-dependent expression of 1,384 genes and 610 intergenic regions. A core group of 251 genes showed pH responses similar to those in a previous study of cultures grown with aeration. The highly acid-induced gene yagU was shown to be required for extreme-acid resistance (survival at pH 2. Acid also up-regulated fimbriae (fimAC, periplasmic chaperones (hdeAB, cyclopropane fatty acid synthase (cfa, and the "constitutive" Na+/H+ antiporter (nhaB. Base up-regulated core genes for maltodextrin transport (lamB, mal, ATP synthase (atp, and DNA repair (recA, mutL. Other genes showed opposite pH responses with or without aeration, for example ETS components (cyo,nuo, sdh and hydrogenases (hya, hyb, hyc, hyf, hyp. A hypF strain lacking all hydrogenase activity showed loss of extreme-acid resistance. Under oxygen limitation only, acid down-regulated ribosome synthesis (rpl,rpm, rps. Acid up-regulated the catabolism of sugar derivatives whose fermentation minimized acid production (gnd, gnt, srl, and also a cluster of 13 genes in the gadA region. Acid up-regulated drug transporters (mdtEF, mdtL, but down-regulated penicillin-binding proteins (dacACD, mreBC. Intergenic regions containing regulatory sRNAs were up-regulated by acid (ryeA, csrB, gadY, rybC. Conclusion pH regulates a core set of genes independently of oxygen, including yagU, fimbriae, periplasmic chaperones, and nha

  4. Transportation Brokerage: An Instructional Module.

    Science.gov (United States)

    Hayden, Linda

    A concept-based introduction to transportation brokerage is provided in this instructional module for undergraduate and graduate transportation-related courses for disciplines such as engineering, business, marketing, and technology. The concept of transportation brokerage is defined as an assignment of the management of a specific element of a…

  5. An in vitro and in silico study on the flavonoid-mediated modulation of the transport of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through Caco-2 monolayers

    NARCIS (Netherlands)

    Schutte, M.E.; Freidig, A.P.; Sandt, J.J.M. van de; Alink, G.M.; Rietjens, I.M.C.M.; Groten, J.P.

    2006-01-01

    The present study describes the effect of different flavonoids on the absorption of the pro-carcinogen PhIP through Caco-2 monolayers and the development of an in silico model describing this process taking into account passive diffusion and active transport of PhIP. Various flavonoids stimulated

  6. An in vitro and in silico study on the flavonoid-mediated modulation of the transport of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through Caco-2 monolayers

    International Nuclear Information System (INIS)

    Schutte, Maaike E.; Freidig, Andreas P.; Sandt, Johannes J.M. van de; Alink, Gerrit M.; Rietjens, Ivonne M.C.M.; Groten, John P.

    2006-01-01

    The present study describes the effect of different flavonoids on the absorption of the pro-carcinogen PhIP through Caco-2 monolayers and the development of an in silico model describing this process taking into account passive diffusion and active transport of PhIP. Various flavonoids stimulated the apical to basolateral PhIP transport. Using the in silico model for flavone, kaempferol and chrysoeriol, the apparent Ki value for inhibition of the active transport to the apical side was estimated to be below 53 μM and for morin, robinetin and taxifolin between 164 and 268 μM. For myricetin, luteolin, naringenin and quercetin, the apparent Ki values were determined more accurately and amounted to 37.3, 12.2, 11.7 and 5.6 μM respectively. Additional experiments revealed that the apical to basolateral PhIP transport was also increased in the presence of a typical BCRP or MRP inhibitor with apparent Ki values in the same range as those of the flavonoids. This observation together with the fact that flavonoids are known to be inhibitors of MRPs and BCRP, corroborates that inhibition of these apical membrane transporters is involved in the flavonoid-mediated increased apical to basolateral PhIP transport. Based on the apparent Ki values obtained, it is concluded that the flavonols, at the levels present in the regular Western diet, are capable of stimulating the transport of PhIP through Caco-2 monolayers from the apical to the basolateral compartment. This points to flavonoid-mediated stimulation of the bioavailability of PhIP and, thus, a possible adverse effect of these supposed beneficial food ingredients

  7. Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus.

    Science.gov (United States)

    Chen, Z L; Huang, R Q

    2014-06-20

    Changes in extracellular pH have a modulatory effect on GABAA receptor function. It has been reported that pH sensitivity of the GABA receptor is dependent on subunit composition and GABA concentration. Most of previous investigations focused on GABA-evoked currents, which only reflect the postsynaptic receptors. The physiological relevance of pH modulation of GABAergic neurotransmission is not fully elucidated. In the present studies, we examined the influence of extracellular pH on the GABAA receptor-mediated inhibitory neurotransmission in rat hypothalamic neurons. The inhibitory postsynaptic currents (IPSCs), tonic currents, and the GABA-evoked currents were recorded with whole-cell patch techniques on the hypothalamic slices from Sprague-Dawley rats at 15-26 postnatal days. The amplitude and frequency of spontaneous GABA IPSCs were significantly increased while the external pH was changed from 7.3 to 8.4. In the acidic pH (6.4), the spontaneous GABA IPSCs were reduced in amplitude and frequency. The pH induced changes in miniature GABA IPSCs (mIPSCs) similar to that in spontaneous IPSCs. The pH effect on the postsynaptic GABA receptors was assessed with exogenously applied varying concentrations of GABA. The tonic currents and the currents evoked by sub-saturating concentration of GABA ([GABA]) (10 μM) were inhibited by acidic pH and potentiated by alkaline pH. In contrast, the currents evoked by saturating [GABA] (1mM) were not affected by pH changes. We also investigated the influence of pH buffers and buffering capacity on pH sensitivity of GABAA receptors on human recombinant α1β2γ2 GABAA receptors stably expressed in HEK 293 cells. The pH influence on GABAA receptors was similar in HEPES- and MES-buffered media, and not dependent on protonated buffers, suggesting that the observed pH effect on GABA response is a specific consequence of changes in extracellular protons. Our data suggest that the hydrogen ions suppress the GABAergic neurotransmission

  8. Cell wall pH and auxin transport velocity

    Science.gov (United States)

    Hasenstein, K. H.; Rayle, D.

    1984-01-01

    According to the chemiosmotic polar diffusion hypothesis, auxin pulse velocity and basal secretion should increase with decreasing cell wall pH. Experiments were designed to test this prediction. Avena coleoptile sections were preincubated in either fusicoccin (FC), cycloheximide, pH 4.0, or pH 8.0 buffer and subsequently their polar transport capacities were determined. Relative to controls, FC enhanced auxin (IAA) uptake while CHI and pH 8.0 buffer reduced IAA uptake. Nevertheless, FC reduced IAA pulse velocity while cycloheximide increased velocity. Additional experiments showed that delivery of auxin to receivers is enhanced by increased receiver pH. This phenomenon was overcome by a pretreatment of the tissue with IAA. Our data suggest that while acidic wall pH values facilitate cellular IAA uptake, they do not enhance pulse velocity or basal secretion. These findings are inconsistent with the chemiosmotic hypothesis for auxin transport.

  9. Acidic pH and short-chain fatty acids activate Na+ transport but differentially modulate expression of Na+/H+ exchanger isoforms 1, 2, and 3 in omasal epithelium.

    Science.gov (United States)

    Lu, Zhongyan; Yao, Lei; Jiang, Zhengqian; Aschenbach, Jörg R; Martens, Holger; Shen, Zanming

    2016-01-01

    Low sodium content in feed and large amounts of salivary sodium secretion are essential requirements to efficient sodium reabsorption in the dairy cow. It is already known that Na(+)/H(+) exchange (NHE) of the ruminal epithelium plays a key role in Na(+) absorption, and its function is influenced by the presence of short-chain fatty acids (SCFA) and mucosal pH. By contrast, the functional role and regulation of NHE in omasal epithelium have not been completely understood. In the present study, we used model studies in small ruminants (sheep and goats) to investigate NHE-mediated Na(+) transport and the effects of pH and SCFA on NHE activity in omasal epithelium and on the expression of NHE isoform in omasal epithelial cells. Conventional Ussing chamber technique, primary cell culture, quantitative PCR, and Western blot were used. In native omasal epithelium of sheep, the Na(+) transport was electroneutral, and it was inhibited by the specific NHE3 inhibitor 3-[2-(3-guanidino-2-methyl-3-oxo-propenyl)-5-methyl-phenyl]-N-isopropylidene-2-methyl-acrylamide dihydrochloride, which decreased mucosal-to-serosal, serosal-to-mucosal, and net flux rates of Na(+) by 80% each. The application of low mucosal pH (6.4 or 5.8) in the presence of SCFA activated the Na(+) transport across omasal epithelium of sheep compared with that at pH 7.4. In cultured omasal epithelial cells of goats, mRNA and protein of NHE1, NHE2, and NHE3 were detected. The application of SCFA increased NHE1 mRNA and protein expression, which was most prominent when the culture medium pH decreased from 7.4 to 6.8. At variance, the mRNA and protein expression of NHE2 and NHE3 were decreased with low pH and SCFA, which was contrary to the published data from ruminal epithelial studies. In conclusion, this paper shows that (1) NHE1, NHE2, and NHE3 are expressed in omasal epithelium; (2) NHE3 mediates the major portion of transepithelial Na(+) transport in omasal epithelium; and (3) SCFA and acidic pH acutely

  10. Public Transportation Pricing: An Instructional Module.

    Science.gov (United States)

    McWha, Charley

    A concept-based introduction to public transportation pricing is presented in this instructional module for undergraduate and graduate transportation-related courses for disciplines such as engineering, business administration, and technology. After an introductory section on transportation pricing planning and the history of transportation system…

  11. Rural Public Transportation: An Instructional Module.

    Science.gov (United States)

    Hayden, Linda

    A concept-based introduction to rural public transportation is provided in this instructional module for undergraduate and graduate transportation-related courses for disciplines such as engineering, business, sociology, and technology. Rural public transportation involves systems in rural and small urban areas with populations under 50,000…

  12. pH and ion strength modulated ionic species loading in mesoporous silica nanoparticles

    International Nuclear Information System (INIS)

    Liu, Wei; Liu, Jianbo; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Yang, Meng; Li, Li; Xu, Jianguo

    2013-01-01

    Mesoporous silica nanoparticles (MSN) have emerged as appealing host materials to accommodate guest molecules for biomedical applications, and recently various methods have been developed to modulate the loading of guest molecules in the silica matrix. Herein, it was demonstrated that pH and ion strength showed great influence on the loading of charged species into the nanoparticles, taking MCM-41 as a host MSN model and methylviologen (MV 2+ ) and 1,5-naphthalene disulfonate (NDS 2− ) as typical charged ionic guest molecules. As the pH increased from 3.0 to 8.0, the loading amount of MV 2+ increased gradually, while on the contrary, it decreased gradually for NDS 2− , for the solution pH changed the electrostatic interaction between the silica matrix and the ionic guest molecules. Additionally, the adding of NaCl reduced the electrostatic interaction, which resulted in a decreasing of the electrostatic rejection and electrostatic accumulation for the molecules carrying the same and the opposite charge to the particle respectively. Thus, pH and ion strength can be employed as simple approaches to modulate the loading of charged molecules and permselectivity in MSN. This work has a definite guidance function for molecule loading, transport modulation, controlled release as well as sensors based on MSN. (paper)

  13. pH Regulatory Transporters in Pancreatic Ductal Adenocarcinoma

    DEFF Research Database (Denmark)

    Kong, Su Chii

    The abnormal features of hypoxia and altered metabolisms in solid tumours lead to an increased glycolysis that is uncoupled from oxidative phosphorylation in the TCA cycle. Tumoural cells often exhibit dysregulated expressions and activities of various membrane pH regulatory transporters to cope...... with the elevated acid production from this glycolysis, as well as from cellular ATP hydrolysis, sequentially creating a favourable intracellular pH and hostile acidic tumour microenvironment, fortify the tumour cells with highly invasive, metastatic and drug resistant phenotype. In current work, we study...... proliferation was found to be decreased while apoptosis was increased with concanamycin A treatment, indicative of V-ATPases being involved in PDAC cell survival mechanisms as well. Comprehending pH regulation in tumour cells might provide insights in preventing tumourigenesis by pH disruptions. Data presented...

  14. Gate modulation of proton transport in a nanopore.

    Science.gov (United States)

    Mei, Lanju; Yeh, Li-Hsien; Qian, Shizhi

    2016-03-14

    Proton transport in confined spaces plays a crucial role in many biological processes as well as in modern technological applications, such as fuel cells. To achieve active control of proton conductance, we investigate for the first time the gate modulation of proton transport in a pH-regulated nanopore by a multi-ion model. The model takes into account surface protonation/deprotonation reactions, surface curvature, electroosmotic flow, Stern layer, and electric double layer overlap. The proposed model is validated by good agreement with the existing experimental data on nanopore conductance with and without a gate voltage. The results show that the modulation of proton transport in a nanopore depends on the concentration of the background salt and solution pH. Without background salt, the gated nanopore exhibits an interesting ambipolar conductance behavior when pH is close to the isoelectric point of the dielectric pore material, and the net ionic and proton conductance can be actively regulated with a gate voltage as low as 1 V. The higher the background salt concentration, the lower is the performance of the gate control on the proton transport.

  15. Organic anion transporting polypeptide 1B transporters modulate hydroxyurea pharmacokinetics

    OpenAIRE

    Walker, Aisha L.; Lancaster, Cynthia S.; Finkelstein, David; Ware, Russell E.; Sparreboom, Alex

    2013-01-01

    Hydroxyurea is currently the only FDA-approved drug that ameliorates the pathophysiology of sickle cell anemia. Unfortunately, substantial interpatient variability in the pharmacokinetics (PK) of hydroxyurea may result in variation of the drug's efficacy. However, little is known about mechanisms that modulate hydroxyurea PK. Recent in vitro studies identifying hydroxyurea as a substrate for organic anion transporting polypeptide (OATP1B) transporters prompted the current investigation assess...

  16. Organic anion transporting polypeptide 1B transporters modulate hydroxyurea pharmacokinetics.

    Science.gov (United States)

    Walker, Aisha L; Lancaster, Cynthia S; Finkelstein, David; Ware, Russell E; Sparreboom, Alex

    2013-12-15

    Hydroxyurea is currently the only FDA-approved drug that ameliorates the pathophysiology of sickle cell anemia. Unfortunately, substantial interpatient variability in the pharmacokinetics (PK) of hydroxyurea may result in variation of the drug's efficacy. However, little is known about mechanisms that modulate hydroxyurea PK. Recent in vitro studies identifying hydroxyurea as a substrate for organic anion transporting polypeptide (OATP1B) transporters prompted the current investigation assessing the role of OATP1B transporters in modulating hydroxyurea PK. Using wild-type and Oatp1b knockout (Oatp1b(-/-)) mice, hydroxyurea PK was analyzed in vivo by measuring [(14)C]hydroxyurea distribution in plasma, kidney, liver, urine, or the exhaled (14)CO2 metabolite. Plasma levels were significantly reduced by 20% in Oatp1b(-/-) mice compared with wild-type (area under the curve of 38.64 or 48.45 μg·h(-1)·ml(-1), respectively) after oral administration, whereas no difference was observed between groups following intravenous administration. Accumulation in the kidney was significantly decreased by twofold in Oatp1b(-/-) mice (356.9 vs. 748.1 pmol/g), which correlated with a significant decrease in urinary excretion. Hydroxyurea accumulation in the liver was also decreased (136.6 vs. 107.3 pmol/g in wild-type or Oatp1b(-/-) mice, respectively) correlating with a decrease in exhaled (14)CO2. These findings illustrate that deficiency of Oatp1b transporters alters the absorption, distribution, and elimination of hydroxyurea thus providing the first in vivo evidence that cell membrane transporters may play a significant role in modulating hydroxyurea PK. Future studies to investigate other transporters and their role in hydroxyurea disposition are warranted for understanding the sources of variation in hydroxyurea's PK.

  17. Thermally modulated biomolecule transport through nanoconfined channels.

    Science.gov (United States)

    Liu, Lei; Zhu, Lizhong

    2015-01-01

    In this work, a nanofluidic device containing both a feed cell and a permeation cell linked by nanopore arrays has been fabricated, which is employed to investigate thermally controlled biomolecular transporting properties through confined nanochannels. The ionic currents modulated by the translocations of goat antibody to human immunoglobulin G (IgG) or bovine serum albumin (BSA) are recorded and analyzed. The results suggest that the modulation effect decreases with the electrolyte concentration increasing, while the effects generated by IgG translocation are more significant than that generated by BSA translocation. More importantly, there is a maximum decreasing value in each modulated current curve with biomolecule concentration increasing for thermally induced intermolecular collision. Furthermore, the turning point for the maximum shifts to lower biomolecule concentrations with the system temperature rising (from 4°C to 45°C), and it is mainly determined by the temperature in the feed cell if the temperature difference exists in the two separated cells. These findings are expected to be valuable for the future design of novel sensing device based on nanopore and/or nanopore arrays.

  18. Plasmodium falciparum chloroquine resistance transporter (PfCRT) isoforms PH1 and PH2 perturb vacuolar physiology.

    Science.gov (United States)

    Callaghan, Paul S; Siriwardana, Amila; Hassett, Matthew R; Roepe, Paul D

    2016-03-31

    Recent work has perfected yeast-based methods for measuring drug transport by the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT). The approach relies on inducible heterologous expression of PfCRT in Saccharomyces cerevisiae yeast. In these experiments selecting drug concentrations are not toxic to the yeast, nor is expression of PfCRT alone toxic. Only when PfCRT is expressed in the presence of CQ is the growth of yeast impaired, due to inward transport of chloroquine (CQ) via the transporter. During analysis of all 53 known naturally occurring PfCRT isoforms, two isoforms (PH1 and PH2 PfCRT) were found to be intrinsically toxic to yeast, even in the absence of CQ. Additional analysis of six very recently identified PfCRT isoforms from Malaysia also showed some toxicity. In this paper the nature of this yeast toxicity is examined. Data also show that PH1 and PH2 isoforms of PfCRT transport CQ with an efficiency intermediate to that catalyzed by previously studied CQR conferring isoforms. Mutation of PfCRT at position 160 is found to perturb vacuolar physiology, suggesting a fitness cost to position 160 amino acid substitutions. These data further define the wide range of activities that exist for PfCRT isoforms found in P. falciparum isolates from around the globe.

  19. Spermidine Biosynthesis and Transport Modulate Pneumococcal Autolysis

    Science.gov (United States)

    Potter, Adam J.

    2014-01-01

    Polyamines are small cationic molecules that have far-reaching roles in biology. In the case of pathogenic bacteria, these functions include those central to their pathogenesis. Streptococcus pneumoniae is a major bacterial pathogen, causing a diverse range of diseases that account for significant morbidity and mortality worldwide. In this work, we characterize the polyamine biosynthetic pathway of S. pneumoniae, demonstrating that this organism produces spermidine from arginine. The synthesis of spermidine was found to be nonessential for growth in a polyamine-free chemically defined medium. However, mutant strains lacking the ability to synthesize or transport spermidine displayed a significant delay in the onset of autolysis. We provide evidence for a model in which spermidine modulates the activity of the major autolysin LytA in the pneumococcal cell wall compartment via interactions with negatively charged molecules, such as teichoic acids. PMID:25092031

  20. Requirements for Ion and Solute Transport, and pH Regulation During Enamel Maturation

    Science.gov (United States)

    LACRUZ, RODRIGO S.; SMITH, CHARLES E.; MOFFATT, PIERRE; CHANG, EUGENE H.; BROMAGE, TIMOTHY G.; BRINGAS, PABLO; NANCI, ANTONIO; BANIWAL, SANJEEV K.; ZABNER, JOSEPH; WELSH, MICHAEL J.; KURTZ, IRA; PAINE, MICHAEL L.

    2012-01-01

    Transcellular bicarbonate transport is suspected to be an important pathway used by ameloblasts to regulate extracellular pH and support crystal growth during enamel maturation. Proteins that play a role in amelogenesis include members of the ABC transporters (SLC gene family and CFTR). A number of carbonic anhydrases (CAs) have also been identified. The defined functions of these genes are likely interlinked during enamel mineralization. The purpose of this study is to quantify relative mRNA levels of individual SLC, Cftr, and CAs in enamel cells obtained from secretory and maturation stages on rat incisors. We also present novel data on the enamel phenotypes for two animal models, amutant porcine(CFTR-ΔF508) and the NBCe1-null mouse.Our data show that two SLCs(AE2 and NBCe1),Cftr,and Car2, Car3,Car6,and Car12 are all significantly up-regulated at the onset of the maturation stage of amelogenesis when compared to the secretory stage. The remaining SLCs and CA gene transcripts showed negligible expression or no significant change in expression from secretory to maturation stages. The enamel of Cftr-ΔF508 adult pigs was hypomineralized and showed abnormal crystal growth. NBCe1-null mice enamel was structurally defective and had a marked decrease in mineral content relative to wild-type. These data demonstrate the importance of many non-matrix proteins to amelogenesis and that the expression levels of multiple genes regulating extracellular pH are modulated during enamel maturation in response to an increased need for pH buffering during hydroxyapatite crystal growth. PMID:21732355

  1. Mechanism of Transport Modulation by an Extracellular Loop in an Archaeal Excitatory Amino Acid Transporter (EAAT) Homolog*

    Science.gov (United States)

    Mulligan, Christopher; Mindell, Joseph A.

    2013-01-01

    Secondary transporters in the excitatory amino acid transporter family terminate glutamatergic synaptic transmission by catalyzing Na+-dependent removal of glutamate from the synaptic cleft. Recent structural studies of the aspartate-specific archaeal homolog, GltPh, suggest that transport is achieved by a rigid body, piston-like movement of the transport domain, which houses the substrate-binding site, between the extracellular and cytoplasmic sides of the membrane. This transport domain is connected to an immobile scaffold by three loops, one of which, the 3–4 loop (3L4), undergoes substrate-sensitive conformational change. Proteolytic cleavage of the 3L4 was found to abolish transport activity indicating an essential function for this loop in the transport mechanism. Here, we demonstrate that despite the presence of fully cleaved 3L4, GltPh is still able to sample conformations relevant for transport. Optimized reconstitution conditions reveal that fully cleaved GltPh retains some transport activity. Analysis of the kinetics and temperature dependence of transport accompanied by direct measurements of substrate binding reveal that this decreased transport activity is not due to alteration of the substrate binding characteristics but is caused by the significantly reduced turnover rate. By measuring solute counterflow activity and cross-link formation rates, we demonstrate that cleaving 3L4 severely and specifically compromises one or more steps contributing to the movement of the substrate-loaded transport domain between the outward- and inward-facing conformational states, sparing the equivalent step(s) during the movement of the empty transport domain. These results reveal a hitherto unknown role for the 3L4 in modulating an essential step in the transport process. PMID:24155238

  2. Position of the third Na+ site in the aspartate transporter GltPh and the human glutamate transporter, EAAT1.

    Directory of Open Access Journals (Sweden)

    Turgut Bastug

    Full Text Available Glutamate transport via the human excitatory amino acid transporters is coupled to the co-transport of three Na(+ ions, one H(+ and the counter-transport of one K(+ ion. Transport by an archaeal homologue of the human glutamate transporters, Glt(Ph, whose three dimensional structure is known is also coupled to three Na(+ ions but only two Na(+ ion binding sites have been observed in the crystal structure of Glt(Ph. In order to fully utilize the Glt(Ph structure in functional studies of the human glutamate transporters, it is essential to understand the transport mechanism of Glt(Ph and accurately determine the number and location of Na(+ ions coupled to transport. Several sites have been proposed for the binding of a third Na(+ ion from electrostatic calculations and molecular dynamics simulations. In this study, we have performed detailed free energy simulations for Glt(Ph and reveal a new site for the third Na(+ ion involving the side chains of Threonine 92, Serine 93, Asparagine 310, Aspartate 312, and the backbone of Tyrosine 89. We have also studied the transport properties of alanine mutants of the coordinating residues Threonine 92 and Serine 93 in Glt(Ph, and the corresponding residues in a human glutamate transporter, EAAT1. The mutant transporters have reduced affinity for Na(+ compared to their wild type counterparts. These results confirm that Threonine 92 and Serine 93 are involved in the coordination of the third Na(+ ion in Glt(Ph and EAAT1.

  3. Basolateral glycylsarcosine (Gly-Sar) transport in Caco-2 cell monolayers is pH dependent

    DEFF Research Database (Denmark)

    Berthelsen, Ragna; Nielsen, Carsten Uhd; Brodin, Birger

    2013-01-01

    Transepithelial di/tripeptide transport in enterocytes occurs via the apical proton-coupled peptide transporter, hPEPT1 (SLC15A1) and a basolateral peptide transporter, which has only been characterized functionally. In this study we examined the pH dependency, substrate uptake kinetics and subst...

  4. Influence of pH on the transport of nanoscale zinc oxide in saturated porous media

    Energy Technology Data Exchange (ETDEWEB)

    Kanel, Sushil R. [Pegasus Technical Services, Inc. (United States); Al-Abed, Souhail R., E-mail: al-abed.souhail@epa.gov [National Risk Management Research Laboratory, U.S. Environmental Protection Agency (United States)

    2011-09-15

    Widespread use of nanoscale zinc oxide (nZnO) in various fields causes subsurface environment contamination. Even though the transport of dissolved zinc ions in subsurface environments such as soils and sediments has been widely studied, the transport mechanism of nZnO in such environments is poorly understood. In addition, nZnO is often combined with stabilizers or dispersing agents to prevent its aggregation in products. The purpose of this study is to determine the influence of pH on the transport properties of pristine nZnO and carboxymethyl cellulose (CMC) stabilized nZnO (CMC-nZnO) suspensions in silica sand packed column under saturated flow conditions. Transport data were collected at different pHs (pHs: 3, 7, 9, and 11) under 1 mL/min flow rate conditions in a 1.1 cm diameter column. It is found that the transport trends of pristine nZnO and CMC-nZnO were different. For pristine nZnO, mobility of total Zn reached a minimum around its point of zero charge (pH 8.9). Whereas in the case of CMC-nZnO, the mobility of total Zn decreased as the pH of the solution pH increased from 3 to 11. ZnO and Zn ion mixture were separated using diafiltration membrane. It showed that most of the nZnO and CMC-nZnO exists as Zn ion at pH 3 before and after eluting from the sand packed column whereas at pH 11, they exist as particles. This study shows the strong influence of pH and stabilizing agents on nZnO transport. These factors should be considered during subsurface transport of nZnO.

  5. Influence of pH on the transport of nanoscale zinc oxide in saturated porous media

    International Nuclear Information System (INIS)

    Kanel, Sushil R.; Al-Abed, Souhail R.

    2011-01-01

    Widespread use of nanoscale zinc oxide (nZnO) in various fields causes subsurface environment contamination. Even though the transport of dissolved zinc ions in subsurface environments such as soils and sediments has been widely studied, the transport mechanism of nZnO in such environments is poorly understood. In addition, nZnO is often combined with stabilizers or dispersing agents to prevent its aggregation in products. The purpose of this study is to determine the influence of pH on the transport properties of pristine nZnO and carboxymethyl cellulose (CMC) stabilized nZnO (CMC–nZnO) suspensions in silica sand packed column under saturated flow conditions. Transport data were collected at different pHs (pHs: 3, 7, 9, and 11) under 1 mL/min flow rate conditions in a 1.1 cm diameter column. It is found that the transport trends of pristine nZnO and CMC–nZnO were different. For pristine nZnO, mobility of total Zn reached a minimum around its point of zero charge (pH 8.9). Whereas in the case of CMC–nZnO, the mobility of total Zn decreased as the pH of the solution pH increased from 3 to 11. ZnO and Zn ion mixture were separated using diafiltration membrane. It showed that most of the nZnO and CMC–nZnO exists as Zn ion at pH 3 before and after eluting from the sand packed column whereas at pH 11, they exist as particles. This study shows the strong influence of pH and stabilizing agents on nZnO transport. These factors should be considered during subsurface transport of nZnO.

  6. Zn2+ modulation of neurotransmitter transporters

    DEFF Research Database (Denmark)

    Nørgaard-Nielsen, K.; Gether, U.

    2006-01-01

    of neurotransmitter transporters have been identified based on sequence homology: (1) the neurotransmitter sodium symporter family (NSS), which includes the Na+/C1(-)-dependent transporters for dopamine, norepinephrine, and serotonin; and (2) the dicarboxylate/amino acid cation symporter family (DAACS), which...

  7. Functional interaction between bicarbonate transporters and carbonic anhydrase modulates lactate uptake into mouse cardiomyocytes.

    Science.gov (United States)

    Peetz, Jan; Barros, L Felipe; San Martín, Alejandro; Becker, Holger M

    2015-07-01

    Blood-derived lactate is a precious energy substrate for the heart muscle. Lactate is transported into cardiomyocytes via monocarboxylate transporters (MCTs) together with H(+), which couples lactate uptake to cellular pH regulation. In this study, we have investigated how the interplay between different acid/base transporters and carbonic anhydrases (CA), which catalyze the reversible hydration of CO2, modulates the uptake of lactate into isolated mouse cardiomyocytes. Lactate transport was estimated both as lactate-induced acidification and as changes in intracellular lactate levels measured with a newly developed Förster resonance energy transfer (FRET) nanosensor. Recordings of intracellular pH showed an increase in the rate of lactate-induced acidification when CA was inhibited by 6-ethoxy-2-benzothiazolesulfonamide (EZA), while direct measurements of lactate flux demonstrated a decrease in MCT transport activity, when CA was inhibited. The data indicate that catalytic activity of extracellular CA increases lactate uptake and counteracts intracellular lactate-induced acidification. We propose a hypothetical model, in which HCO3 (-), formed from cell-derived CO2 at the outer surface of the cardiomyocyte plasma membrane by membrane-anchored, extracellular CA, is transported into the cell via Na(+)/HCO3 (-) cotransport to counteract intracellular acidification, while the remaining H(+) stabilizes extracellular pH at the surface of the plasma membrane during MCT activity to enhance lactate influx into cardiomyocytes.

  8. Alkaline pH activates the transport activity of GLUT1 in L929 fibroblast cells.

    Science.gov (United States)

    Gunnink, Stephen M; Kerk, Samuel A; Kuiper, Benjamin D; Alabi, Ola D; Kuipers, David P; Praamsma, Riemer C; Wrobel, Kathryn E; Louters, Larry L

    2014-04-01

    The widely expressed mammalian glucose transporter, GLUT1, can be acutely activated in L929 fibroblast cells by a variety of conditions, including glucose deprivation, or treatment with various respiration inhibitors. Known thiol reactive compounds including phenylarsine oxide and nitroxyl are the fastest acting stimulators of glucose uptake, implicating cysteine biochemistry as critical to the acute activation of GLUT1. In this study, we report that in L929 cells glucose uptake increases 6-fold as the pH of the uptake solution is increased from 6 to 9 with the half-maximal activation at pH 7.5; consistent with the pKa of cysteine residues. This pH effect is essentially blocked by the pretreatment of the cells with either iodoacetamide or cinnamaldehyde, compounds that form covalent adducts with reduced cysteine residues. In addition, the activation by alkaline pH is not additive at pH 8 with known thiol reactive activators such as phenylarsine oxide or hydroxylamine. Kinetic analysis in L929 cells at pH 7 and 8 indicate that alkaline conditions both increases the Vmax and decreases the Km of transport. This is consistent with the observation that pH activation is additive to methylene blue, which activates uptake by increasing the Vmax, as well as to berberine, which activates uptake by decreasing the Km. This suggests that cysteine biochemistry is utilized in both methylene blue and berberine activation of glucose uptake. In contrast a pH increase from 7 to 8 in HCLE cells does not further activate glucose uptake. HCLE cells have a 25-fold higher basal glucose uptake rate than L929 cells and the lack of a pH effect suggests that the cysteine biochemistry has already occurred in HCLE cells. The data are consistent with pH having a complex mechanism of action, but one likely mediated by cysteine biochemistry. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Coral calcifying fluid pH is modulated by seawater carbonate chemistry not solely seawater pH.

    Science.gov (United States)

    Comeau, S; Tambutté, E; Carpenter, R C; Edmunds, P J; Evensen, N R; Allemand, D; Ferrier-Pagès, C; Tambutté, S; Venn, A A

    2017-01-25

    Reef coral calcification depends on regulation of pH in the internal calcifying fluid (CF) in which the coral skeleton forms. However, little is known about calcifying fluid pH (pH CF ) regulation, despite its importance in determining the response of corals to ocean acidification. Here, we investigate pH CF in the coral Stylophora pistillata in seawater maintained at constant pH with manipulated carbonate chemistry to alter dissolved inorganic carbon (DIC) concentration, and therefore total alkalinity (A T ). We also investigate the intracellular pH of calcifying cells, photosynthesis, respiration and calcification rates under the same conditions. Our results show that despite constant pH in the surrounding seawater, pH CF is sensitive to shifts in carbonate chemistry associated with changes in [DIC] and [A T ], revealing that seawater pH is not the sole driver of pH CF Notably, when we synthesize our results with published data, we identify linear relationships of pH CF with the seawater [DIC]/[H + ] ratio, [A T ]/ [H + ] ratio and [[Formula: see text

  10. Astrocytic GABA transporter activity modulates excitatory neurotransmission

    DEFF Research Database (Denmark)

    Boddum, Kim; Jensen, Thomas P.; Magloire, Vincent

    2016-01-01

    unrecognized role for the astrocytic GABA transporter, GAT-3. GAT-3 activity results in a rise in astrocytic Na(+) concentrations and a consequent increase in astrocytic Ca(2+) through Na(+)/Ca(2+) exchange. This leads to the release of ATP/adenosine by astrocytes, which then diffusely inhibits neuronal...

  11. pH modulates the binding of early growth response protein 1 transcription factor to DNA.

    Science.gov (United States)

    Mikles, David C; Bhat, Vikas; Schuchardt, Brett J; Deegan, Brian J; Seldeen, Kenneth L; McDonald, Caleb B; Farooq, Amjad

    2013-08-01

    The transcription factor early growth response protein (EGR)1 orchestrates a plethora of signaling cascades involved in cellular homeostasis, and its downregulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with an increase in pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as His382 by virtue of the fact that its replacement by nonionizable residues abolishes the pH dependence of the binding of EGR1 to DNA. Notably, His382 inserts into the major groove of DNA, and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, His382 is mainly conserved across other members of the EGR family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating the protein-DNA interactions that are central to this family of transcription factors. Collectively, our findings reveal an unexpected but a key step in the molecular recognition of the EGR family of transcription factors, and suggest that they may act as sensors of pH within the intracellular environment. © 2013 FEBS.

  12. Effects of high medium pH on growth, metabolism and transport in Saccharomyces cerevisiae.

    Science.gov (United States)

    Peña, Antonio; Sánchez, Norma Silvia; Álvarez, Helber; Calahorra, Martha; Ramírez, Jorge

    2015-03-01

    Growth of Saccharomyces cerevisiae stopped by maintaining the pH of the medium in a pH-stat at pH 8.0 or 9.0. Studying its main physiological capacities and comparing cells after incubation at pH 6.0 vs. 8.0 or 9.0, we found that (a) fermentation was moderately decreased by high pH and respiration was similar and sensitive to the addition of an uncoupler, (b) ATP and glucose-6-phosphate levels upon glucose addition increased to similar levels and (c) proton pumping and K(+) transport were also not affected; all this indicating that energy mechanisms were preserved. Growth inhibition at high pH was also not due to a significant lower amino acid transport by the cells or incorporation into proteins. The cell cycle stopped at pH 9.0, probably due to an arrest as a result of adjustments needed by the cells to contend with the changes under these conditions, and microarray experiments showed some relevant changes to this response. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  13. GABA signalling modulates plant growth by directly regulating the activity of plant-specific anion transporters.

    Science.gov (United States)

    Ramesh, Sunita A; Tyerman, Stephen D; Xu, Bo; Bose, Jayakumar; Kaur, Satwinder; Conn, Vanessa; Domingos, Patricia; Ullah, Sana; Wege, Stefanie; Shabala, Sergey; Feijó, José A; Ryan, Peter R; Gilliham, Matthew; Gillham, Matthew

    2015-07-29

    The non-protein amino acid, gamma-aminobutyric acid (GABA) rapidly accumulates in plant tissues in response to biotic and abiotic stress, and regulates plant growth. Until now it was not known whether GABA exerts its effects in plants through the regulation of carbon metabolism or via an unidentified signalling pathway. Here, we demonstrate that anion flux through plant aluminium-activated malate transporter (ALMT) proteins is activated by anions and negatively regulated by GABA. Site-directed mutagenesis of selected amino acids within ALMT proteins abolishes GABA efficacy but does not alter other transport properties. GABA modulation of ALMT activity results in altered root growth and altered root tolerance to alkaline pH, acid pH and aluminium ions. We propose that GABA exerts its multiple physiological effects in plants via ALMT, including the regulation of pollen tube and root growth, and that GABA can finally be considered a legitimate signalling molecule in both the plant and animal kingdoms.

  14. Regulation of the glutamine transporter SN1 by extracellular pH and intracellular sodium ions

    International Nuclear Information System (INIS)

    Broeer, A.; Broeer, S.; Setiawan, I.; Lang, F.

    2001-01-01

    Full text: SN1 has recently been identified as one of the major glutamine transporters in hepatocytes and brain astrocytes. It appears to be the molecular correlate of the system N amino acid transporter. Two different transport mechanisms have been proposed for this transporter. Either an electroneutral mechanism, in which glutamine uptake is coupled to an exchange of 1Na + and 1H + , or an electrogenic mechanism coupled to the exchange of 2Na + against 1H + . This study was performed to solve the discrepancies and to investigate the reversibility of the transporter. When expressed in Xenopus laevis oocytes glutamine uptake activity increased strongly with increasing pH. In agreement with the pH-dependence we found that uptake of glutamine was accompanied by an alkalization of the cytosol, indicating that SN1 mediates Glutamine/H + -Antiport. Uptake of glutamine into oocytes was Na + -dependent. Analysis of the Na + -dependence of glutamine transport and Flux studies using 22 Na + indicated that two or more sodium ions were cotransported together with glutamine. However, at the same time intracellular Na + was exchanged against extracellular Na + . Taken together with the results of the pH-dependence it is proposed that SN1 mediates a Na + /Na + -exchange and a Na + /H + -exchange, both being coupled to the transport of glutamine. In agreement with this mechanism we found that acidic pH caused a reversal of the transporter. To investigate the source of the glutamine-induced inward currents, we compared inward currents generated by the 1Na + /glutamine cotransporter ATA1 with those generated by SN1. Currents induced by glutamine uptake in SN1 expressing oocytes were only a fraction of the currents induced by glutamine in ATA1 expressing oocytes, indicating that they were not generated by a stoichiometric uptake of ions. It is concluded that SN1 is tightly regulated by pH and intracellular Na + -ions and is capable of mediating glutamine uptake and release

  15. pH modulates arsenic toxicity in Bacillus licheniformis DAS-2.

    Science.gov (United States)

    Tripti, K; Shardendu

    2016-08-01

    The toxic characteristics of arsenic species, As(V) and As(III) result in ecological risks. Arsenic tolerant bacterium was isolated and identified as the Bacillus licheniformis DAS-2 through 16SrDNA sequencing. B. licheniformis DAS-2 was efficient to tolerate and remove both the As(V)[MIC 8mM] and As(III)[MIC 6mM] from the growth medium. The potential for the removal/uptake of arsenic from the 3, 5 and 7mM As(V) enriched growth media was 100%, 60% and 35% respectively and from the 1, 3 and 5mM As(III) enrichment it was 100%, 99% and 58% respectively at neutral pH. 80% of uptake As(V) was reduced to As(III) in 3mM As(V) enrichment which was gradually decreased to only 17% at 7mM As(V) enrichment at neutral pH. The arsenic toxicity in B. licheniformis DAS-2 was found modulated by pH and was examined through alteration in growth, uptake/removal, reduction and measurement of chemical toxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. pH Modulates the Binding of EGR1 Transcription Factor to DNA

    Science.gov (United States)

    Mikles, David C.; Bhat, Vikas; Schuchardt, Brett J.; Deegan, Brian J.; Seldeen, Kenneth L.; McDonald, Caleb B.; Farooq, Amjad

    2013-01-01

    EGR1 transcription factor orchestrates a plethora of signaling cascades involved in cellular homeostasis and its down-regulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with increasing pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as H382 by virtue of the fact that its substitution to non-ionizable residues abolishes pH-dependence of the binding of EGR1 to DNA. Notably, H382 inserts into the major groove of DNA and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, H382 is predominantly conserved across other members of EGR1 family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating protein-DNA interactions central to this family of transcription factors. Collectively, our findings uncover an unexpected but a key step in the molecular recognition of EGR1 family of transcription factors and suggest that they may act as sensors of pH within the intracellular environment. PMID:23718776

  17. Influence of culture medium pH on charasome development and chloride transport in Chara corallina

    International Nuclear Information System (INIS)

    Lucas, W.J.; Keifer, D.W.; Pesacreta, T.C.

    1986-01-01

    Internodal cells of Chara, grown in culture either at pH 5.7,6.5 or 7.5, were studied to determine their chloride influx capability, the quantitative aspects of charasome morphology and the degree to which these two parameters could be correlated. In cells grown at pH 5.7 the charasomes were relatively small, were widely spaced on the plasma membrane, and contributed only at 0.6% increase to the surface area of the plasma membrane in the acid region of the cell. In contrast, the charasome membrane surface area of cells grown at pH 7.5 had increased x 19, the density of charasomes on the cell surface increased x 42, thus producing a x 3.57 increase in the acid region plasma membrane surface area. Chloride influx in cells grown at pH 7.5 was x 8.7-12.7 greater than in cells grown at pH 5.7. Cells that had been starved of chloride exhibited a x 2.4 average increase in the rate of chloride influx. Our observations establish the existence of a positive correlation between the rate of chloride influx and the increase in membran surface area due to charasomes, although other factors, such as the effect of pH on transport-related enzymes, and the effect of charasome structure on chemical equilibria, may also be of importance. (Author)

  18. Effects of pH on nano-bubble stability and transport in saturated porous media

    Science.gov (United States)

    Hamamoto, Shoichiro; Takemura, Takato; Suzuki, Kenichiro; Nishimura, Taku

    2018-01-01

    An understanding of nano-scale bubble (NB) transport in porous media is important for potential application of NBs in soil/groundwater remediation. It is expected that the solution chemistry of NB water highly influences the surface characteristics of NBs and porous media and the interaction between them, thus affecting the stability and transport characteristics of NB. In this study, in addition to stability experiments, one-dimensional column transport experiments using glass beads were conducted to investigate the effects of pH on the NB transport behavior. The results showed that the NBs were more stable under higher pH. Column transport experiments revealed that entrapment of NBs, especially larger ones, was enhanced in lower-pH water, likely suggesting pH-dependent NB attachment and physical straining, both of which are also probably influenced by bubble size. Although relatively smaller NBs were released after switching the eluting fluid to one with lower ionic strength, most of the NBs in lower-pH water were still retained in the porous media even altering the chemical condition.

  19. Inverse pH regulation of plant and fungal sucrose transporters: a mechanism to regulate competition for sucrose at the host/pathogen interface?

    Directory of Open Access Journals (Sweden)

    Kathrin Wippel

    Full Text Available BACKGROUND: Plant sucrose transporter activities were shown to respond to changes in the extracellular pH and redox status, and oxidizing compounds like glutathione (GSSG or H(2O(2 were reported to effect the subcellular targeting of these proteins. We hypothesized that changes in both parameters might be used to modulate the activities of competing sucrose transporters at a plant/pathogen interface. We, therefore, compared the effects of redox-active compounds and of extracellular pH on the sucrose transporters UmSRT1 and ZmSUT1 known to compete for extracellular sucrose in the Ustilago maydis (corn smut/Zea mays (maize pathosystem. METHODOLOGY/PRINCIPAL FINDINGS: We present functional analyses of the U. maydis sucrose transporter UmSRT1 and of the plant sucrose transporters ZmSUT1 and StSUT1 in Saccharomyces cerevisiae or in Xenopus laevis oocytes in the presence of different extracellular pH-values and redox systems, and study the possible effects of these treatments on the subcellular targeting. We observed an inverse regulation of host and pathogen sucrose transporters by changes in the apoplastic pH. Under none of the conditions analyzed, we could confirm the reported effects of redox-active compounds. CONCLUSIONS/SIGNIFICANCE: Our data suggest that changes in the extracellular pH but not of the extracellular redox status might be used to oppositely adjust the transport activities of plant and fungal sucrose transporters at the host/pathogen interface.

  20. Transport in a magnetic field modulated graphene superlattice.

    Science.gov (United States)

    Li, Yu-Xian

    2010-01-13

    Using the transfer matrix method, we study the transport properties through a magnetic field modulated graphene superlattice. It is found that the electrostatic barrier, the magnetic vector potential, and the number of wells in a superlattice modify the transmission remarkably. The angular dependent transmission is blocked by the magnetic vector potential because of the appearance of the evanescent states at certain incident angles, and the region of Klein tunneling shifts to the left. The angularly averaged conductivities exhibit oscillatory behavior. The magnitude and period of oscillation depend sensitively on the height of the electrostatic barrier, the number of wells, and the strength of the modulated magnetic field.

  1. Packaging, Transportation and Recycling of NPP Condenser Modules - 12262

    Energy Technology Data Exchange (ETDEWEB)

    Polley, G.M. [Perma-Fix Environmental Services, 575 Oak Ridge Turnpike, Oak Ridge, TN 37830 (United States)

    2012-07-01

    Perma-Fix was awarded contract from Energy Northwest for the packaging, transportation and disposition of the condenser modules, water boxes and miscellaneous metal, combustibles and water generated during the 2011 condenser replacement outage at the Columbia Generating Station. The work scope was to package the water boxes and condenser modules as they were removed from the facility and transfer them to the Perma-Fix Northwest facility for processing, recycle of metals and disposition. The condenser components were oversized and overweight (the condenser modules weighed ∼102,058 kg [225,000 lb]) which required special equipment for loading and transport. Additional debris waste was packaged in inter-modals and IP-1 boxes for transport. A waste management plan was developed to minimize the generation of virtually any waste requiring landfill disposal. The Perma-Fix Northwest facility was modified to accommodate the ∼15 m [50-ft] long condenser modules and equipment was designed and manufactured to complete the disassembly, decontamination and release survey. The condenser modules are currently undergoing processing for free release to a local metal recycler. Over three millions pounds of metal will be recycled and over 95% of the waste generated during this outage will not require land disposal. There were several elements of this project that needed to be addressed during the preparation for this outage and the subsequent packaging, transportation and processing. - Staffing the project to support 24/7 generation of large components and other wastes. - The design and manufacture of the soft-sided shipping containers for the condenser modules that measured ∼15 m X 4 m X 3 m [50 ft X 13 ft X 10 ft] and weighed ∼102,058 kg [225,000 lbs] - Developing a methodology for loading the modules into the shipping containers. - Obtaining a transport vehicle for the modules. - Designing and modifying the processing facility. - Movement of the modules at the processing

  2. Physics basis of Multi-Mode anomalous transport module

    Energy Technology Data Exchange (ETDEWEB)

    Rafiq, T.; Kritz, A. H.; Luo, L. [Department of Physics, Lehigh University, Bethlehem, Pennsylvania 18015 (United States); Weiland, J. [Departments of Applied Physics, Chalmers University of Technology and Euratom-VR Assoc., S41296 Gothenburg (Sweden); Pankin, A. Y. [Tech-X Corporation, Boulder, Colorado (United States)

    2013-03-15

    The derivation of Multi-Mode anomalous transport module version 8.1 (MMM8.1) is presented. The MMM8.1 module is advanced, relative to MMM7.1, by the inclusion of peeling modes, dependence of turbulence correlation length on flow shear, electromagnetic effects in the toroidal momentum diffusivity, and the option to compute poloidal momentum diffusivity. The MMM8.1 model includes a model for ion temperature gradient, trapped electron, kinetic ballooning, peeling, collisionless and collision dominated magnetohydrodynamics modes as well as model for electron temperature gradient modes, and a model for drift resistive inertial ballooning modes. In the derivation of the MMM8.1 module, effects of collisions, fast ion and impurity dilution, non-circular flux surfaces, finite beta, and Shafranov shift are included. The MMM8.1 is used to compute thermal, particle, toroidal, and poloidal angular momentum transports. The fluid approach which underlies the derivation of MMM8.1 is expected to reliably predict, on an energy transport time scale, the evolution of temperature, density, and momentum profiles in plasma discharges for a wide range of plasma conditions.

  3. Effect of pH and soil structure on transport of sulfonamide antibiotics in agricultural soils.

    Science.gov (United States)

    Park, Jong Yol; Huwe, Bernd

    2016-06-01

    We investigated the effect of solution pH and soil structure on transport of sulfonamide antibiotics (sulfamethoxazole, sulfadimethoxine and sulfamethazine) in combination with batch sorption tests and column experiments. Sorption isotherms properly conformed to Freundlich model, and sorption potential of the antibiotics is as follows; sulfadimethoxine > sulfamethoxazole > sulfamethazine. Decreasing pH values led to increased sorption potential of the antibiotics on soil material in pH range of 4.0-8.0. This likely resulted from abundance of neutral and positive-charged sulfonamides species at low pH, which electrostatically bind to sorption sites on soil surface. Due to destruction of macropore channels, lower hydraulic conductivities of mobile zone were estimated in the disturbed soil columns than in the undisturbed soil columns, and eventually led to lower mobility of the antibiotics in disturbed column. The results suggest that knowledge of soil structure and solution condition is required to predict fate and distribution of sulfonamide antibiotics in environmental matrix. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Flavonoids as modulators of metabolic enzymes and drug transporters.

    Science.gov (United States)

    Miron, Anca; Aprotosoaie, Ana Clara; Trifan, Adriana; Xiao, Jianbo

    2017-06-01

    Flavonoids, natural compounds found in plants and in plant-derived foods and beverages, have been extensively studied with regard to their capacity to modulate metabolic enzymes and drug transporters. In vitro, flavonoids predominantly inhibit the major phase I drug-metabolizing enzyme CYP450 3A4 and the enzymes responsible for the bioactivation of procarcinogens (CYP1 enzymes) and upregulate the enzymes involved in carcinogen detoxification (UDP-glucuronosyltransferases, glutathione S-transferases (GSTs)). Flavonoids have been reported to inhibit ATP-binding cassette (ABC) transporters (multidrug resistance (MDR)-associated proteins, breast cancer-resistance protein) that contribute to the development of MDR. P-glycoprotein, an ABC transporter that limits drug bioavailability and also induces MDR, was differently modulated by flavonoids. Flavonoids and their phase II metabolites (sulfates, glucuronides) inhibit organic anion transporters involved in the tubular uptake of nephrotoxic compounds. In vivo studies have partially confirmed in vitro findings, suggesting that the mechanisms underlying the modulatory effects of flavonoids are complex and difficult to predict in vivo. Data summarized in this review strongly support the view that flavonoids are promising candidates for the enhancement of oral drug bioavailability, chemoprevention, and reversal of MDR. © 2017 New York Academy of Sciences.

  5. Importance of bicarbonate transport in pH control during amelogenesis - need for functional studies.

    Science.gov (United States)

    Varga, G; DenBesten, P; Rácz, R; Zsembery, Á

    2017-08-18

    Dental enamel, the hardest mammalian tissue, is produced by ameloblasts. Ameloblasts show many similarities to other transporting epithelia although their secretory product, the enamel matrix, is quite different. Ameloblasts direct the formation of hydroxyapatite crystals, which liberate large quantities of protons that then need to be buffered to allow mineralization to proceed. Buffering requires a tight pH regulation and secretion of bicarbonate by ameloblasts. Many investigations have used immunohistochemical and knockout studies to determine the effects of these genes on enamel formation, but up till recently very little functional data were available for mineral ion transport. To address this, we developed a novel 2D in vitro model using HAT-7 ameloblast cells. HAT-7 cells can be polarized and develop functional tight junctions. Furthermore, they are able to accumulate bicarbonate ions from the basolateral to the apical fluid spaces. We propose that in the future, the HAT-7 2D system along with similar cellular models will be useful to functionally model ion transport processes during amelogenesis. Additionally, we also suggest that similar approaches will allow a better understanding of the regulation of the cycling process in maturation-stage ameloblasts, and the pH sensory mechanisms, which are required to develop sound, healthy enamel. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  6. Modulation of the epithelial Ca2+ channel ECaC by extracellular pH.

    NARCIS (Netherlands)

    Vennekens, R.; Prenen, J.; Hoenderop, J.G.J.; Bindels, R.J.M.; Droogmans, G.; Nilius, B.

    2001-01-01

    We investigated the effect of extracellular pH on whole-cell currents through the epithelial Ca2+ channel, ECaC, expressed in HEK 293 cells. Both mono- and divalent current densities were significantly smaller at pH 6.0 than at pH 7.4. At pH 8.5 they were slightly larger. Lowering extracellular pH

  7. Ameloblast Modulation and Transport of Cl⁻, Na⁺, and K⁺ during Amelogenesis.

    Science.gov (United States)

    Bronckers, A L J J; Lyaruu, D; Jalali, R; Medina, J F; Zandieh-Doulabi, B; DenBesten, P K

    2015-12-01

    Ameloblasts express transmembrane proteins for transport of mineral ions and regulation of pH in the enamel space. Two major transporters recently identified in ameloblasts are the Na(+)K(+)-dependent calcium transporter NCKX4 and the Na(+)-dependent HPO4 (2-) (Pi) cotransporter NaPi-2b. To regulate pH, ameloblasts express anion exchanger 2 (Ae2a,b), chloride channel Cftr, and amelogenins that can bind protons. Exposure to fluoride or null mutation of Cftr, Ae2a,b, or Amelx each results in formation of hypomineralized enamel. We hypothesized that enamel hypomineralization associated with disturbed pH regulation results from reduced ion transport by NCKX4 and NaPi-2b. This was tested by correlation analyses among the levels of Ca, Pi, Cl, Na, and K in forming enamel of mice with null mutation of Cftr, Ae2a,b, and Amelx, according to quantitative x-ray electron probe microanalysis. Immunohistochemistry, polymerase chain reaction analysis, and Western blotting confirmed the presence of apical NaPi-2b and Nckx4 in maturation-stage ameloblasts. In wild-type mice, K levels in enamel were negatively correlated with Ca and Cl but less negatively or even positively in fluorotic enamel. Na did not correlate with P or Ca in enamel of wild-type mice but showed strong positive correlation in fluorotic and nonfluorotic Ae2a,b- and Cftr-null enamel. In hypomineralizing enamel of all models tested, 1) Cl(-) was strongly reduced; 2) K(+) and Na(+) accumulated (Na(+) not in Amelx-null enamel); and 3) modulation was delayed or blocked. These results suggest that a Na(+)K(+)-dependent calcium transporter (likely NCKX4) and a Na(+)-dependent Pi transporter (potentially NaPi-2b) located in ruffle-ended ameloblasts operate in a coordinated way with the pH-regulating machinery to transport Ca(2+), Pi, and bicarbonate into maturation-stage enamel. Acidification and/or associated physicochemical/electrochemical changes in ion levels in enamel fluid near the apical ameloblast membrane may

  8. Ameloblast modulation and transport of Cl-, Na+, and K+ during amelogenesis

    NARCIS (Netherlands)

    Bronckers, A.L.J.J.; Lyaruu, D.; Jalali, R.; Medina, J.F.; Zandieh-Doulabi, B.; DenBesten, P.K.

    2015-01-01

    Ameloblasts express transmembrane proteins for transport of mineral ions and regulation of pH in the enamel space. Two major transporters recently identified in ameloblasts are the Na+K+-dependent calcium transporter NCKX4 and the Na+-dependent HPO42- (Pi) cotransporter NaPi-2b. To regulate pH,

  9. Modulating Pluronics micellar rupture with cyclodextrins and drugs: effect of pH and temperature

    International Nuclear Information System (INIS)

    Valero, M; Dreiss, C A

    2014-01-01

    Micelles of the triblock copolymer Pluronic F127 can encapsulate drugs with various chemical structures and their architecture has been studied by small-angle neutron scattering (SANS). Interaction with a derivative of β-cyclodextrin, namely, heptakis(2,6-di-O- methyl)-β-cyclodextrin (DIMEB), induces a complete break-up of the micelles, providing a mechanism for drug release. In the presence of drugs partitioned within the micelles, competitive interactions between polymer, drug and cyclodextrin lead to a modulation of the micellar rupture, depending on the nature of the drug and the exact composition of the ternary system. These interactions can be further adjusted by temperature and pH. While the most widely accepted mechanism for the interaction between Pluronics and cyclodextrins is through polypseudorotaxane (PR) formation, involving the threading of β-CD on the polymer backbone, time-resolved SANS experiments show that de-micellisation takes place in less than 100 ms, thus unambiguously ruling out an inclusion complex between the cyclodextrin and the polymer chains

  10. Importance of pH Homeostasis in Metabolic Health and Diseases: Crucial Role of Membrane Proton Transport

    Directory of Open Access Journals (Sweden)

    Wataru Aoi

    2014-01-01

    Full Text Available Protons dissociated from organic acids in cells are partly buffered. If not, they are transported to the extracellular fluid through the plasma membrane and buffered in circulation or excreted in urine and expiration gas. Several transporters including monocarboxylate transporters and Na+/H+ exchanger play an important role in uptake and output of protons across plasma membranes in cells of metabolic tissues including skeletal muscle and the liver. They also contribute to maintenance of the physiological pH of body fluid. Therefore, impairment of these transporters causes dysfunction of cells, diseases, and a decrease in physical performance associated with abnormal pH. Additionally, it is known that fluid pH in the interstitial space of metabolic tissues is easily changed due to little pH buffering capacitance in interstitial fluids and a reduction in the interstitial fluid pH may mediate the onset of insulin resistance unlike blood containing pH buffers such as Hb (hemoglobin and albumin. In contrast, habitual exercise and dietary intervention regulate expression/activity of transporters and maintain body fluid pH, which could partly explain the positive effect of healthy lifestyle on disease prognosis.

  11. MELCOR aerosol transport module modification for NSSR-1

    International Nuclear Information System (INIS)

    Merrill, B.J.; Hagrman, D.L.

    1996-03-01

    This report describes modifications of the MELCOR computer code aerosol transport module that will increase the accuracy of calculations for safety analysis of the International Thermonuclear Experimental Reactor (ITER). The modifications generalize aerosol deposition models to consider gases other than air, add specialized models for aerosol deposition during high speed gas flows in ducts, and add models for resuspension of aerosols that are entrained in coolants when these coolants flash. Particular attention has been paid to the adhesion of aerosol particles once they are transported to duct walls. The results of calculations with the modified models have been successfully compared to data from Light Water Reactor Aerosol Containment Experiments (LACE) conducted by an international consortium at Hanford, Washington

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

    Science.gov (United States)

    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.

  13. Plasmodium falciparum chloroquine resistance transporter (PfCRT) isoforms PH1 and PH2 perturb vacuolar physiology

    OpenAIRE

    Callaghan, Paul S.; Siriwardana, Amila; Hassett, Matthew R.; Roepe, Paul D.

    2016-01-01

    Background Recent work has perfected yeast-based methods for measuring drug transport by the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT). Methods The approach relies on inducible heterologous expression of PfCRT in Saccharomyces cerevisiae yeast. In these experiments selecting drug concentrations are not toxic to the yeast, nor is expression of PfCRT alone toxic. Only when PfCRT is expressed in the presence of CQ is the growth of yeast impaired, due to inward transpo...

  14. Tritium transport calculations for the IFMIF Tritium Release Test Module

    Energy Technology Data Exchange (ETDEWEB)

    Freund, Jana, E-mail: jana.freund@kit.edu; Arbeiter, Frederik; Abou-Sena, Ali; Franza, Fabrizio; Kondo, Keitaro

    2014-10-15

    Highlights: • Delivery of material data for the tritium balance in the IFMIF Tritium Release Test Module. • Description of the topological models in TMAP and the adapted fusion-devoted Tritium Permeation Code (FUS-TPC). • Computation of release of tritium from the breeder solid material into the purge gas. • Computation of the loss of tritium over the capsule wall, rig hull, container wall and purge gas return line. - Abstract: The IFMIF Tritium Release Test Module (TRTM) is projected to measure online the tritium release from breeder ceramics and beryllium pebble beds under high energy neutron irradiation. Tritium produced in the pebble bed of TRTM is swept out continuously by a purge gas flow, but can also permeate into the module's metal structures, and can be lost by permeation to the environment. According analyses on the tritium inventory are performed to support IFMIF plant safety studies, and to support the experiment planning. This paper describes the necessary elements for calculation of the tritium transport in the Tritium Release Test Module as follows: (i) applied equations for the tritium balance, (ii) material data from literature and (iii) the topological models and the computation of the five different cases; namely release of tritium from the breeder solid material into the purge gas, loss of tritium over the capsule wall, rig hull, container wall and purge gas return line in detail. The problem of tritium transport in the TRTM has been studied and analyzed by the Tritium Migration Analysis Program (TMAP) and the adapted fusion-devoted Tritium Permeation Code (FUS-TPC). TMAP has been developed at INEEL and now exists in Version 7. FUS-TPC Code was written in MATLAB with the original purpose to study the tritium transport in Helium Cooled Lead Lithium (HCLL) blanket and in a later version the Helium Cooled Pebble Bed (HCPB) blanket by [6] (Franza, 2012). This code has been further modified to be applicable to the TRTM. Results from the

  15. Tritium transport calculations for the IFMIF Tritium Release Test Module

    International Nuclear Information System (INIS)

    Freund, Jana; Arbeiter, Frederik; Abou-Sena, Ali; Franza, Fabrizio; Kondo, Keitaro

    2014-01-01

    Highlights: • Delivery of material data for the tritium balance in the IFMIF Tritium Release Test Module. • Description of the topological models in TMAP and the adapted fusion-devoted Tritium Permeation Code (FUS-TPC). • Computation of release of tritium from the breeder solid material into the purge gas. • Computation of the loss of tritium over the capsule wall, rig hull, container wall and purge gas return line. - Abstract: The IFMIF Tritium Release Test Module (TRTM) is projected to measure online the tritium release from breeder ceramics and beryllium pebble beds under high energy neutron irradiation. Tritium produced in the pebble bed of TRTM is swept out continuously by a purge gas flow, but can also permeate into the module's metal structures, and can be lost by permeation to the environment. According analyses on the tritium inventory are performed to support IFMIF plant safety studies, and to support the experiment planning. This paper describes the necessary elements for calculation of the tritium transport in the Tritium Release Test Module as follows: (i) applied equations for the tritium balance, (ii) material data from literature and (iii) the topological models and the computation of the five different cases; namely release of tritium from the breeder solid material into the purge gas, loss of tritium over the capsule wall, rig hull, container wall and purge gas return line in detail. The problem of tritium transport in the TRTM has been studied and analyzed by the Tritium Migration Analysis Program (TMAP) and the adapted fusion-devoted Tritium Permeation Code (FUS-TPC). TMAP has been developed at INEEL and now exists in Version 7. FUS-TPC Code was written in MATLAB with the original purpose to study the tritium transport in Helium Cooled Lead Lithium (HCLL) blanket and in a later version the Helium Cooled Pebble Bed (HCPB) blanket by [6] (Franza, 2012). This code has been further modified to be applicable to the TRTM. Results from the

  16. Intracellular pH regulation by acid-base transporters in mammalian neurons

    Science.gov (United States)

    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

  17. The acid test of fluoride: how pH modulates toxicity.

    Directory of Open Access Journals (Sweden)

    Ramaswamy Sharma

    2010-05-01

    Full Text Available It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F(-. Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of F(-. Enamel formation is initiated in a neutral pH environment (secretory stage; however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage. Low pH can facilitate entry of F(- into cells. Here, we asked if F(- was more toxic at low pH, as measured by increased cell stress and decreased cell function.Treatment of ameloblast-derived LS8 cells with F(- at low pH reduced the threshold dose of F(- required to phosphorylate stress-related proteins, PERK, eIF2alpha, JNK and c-jun. To assess protein secretion, LS8 cells were stably transduced with a secreted reporter, Gaussia luciferase, and secretion was quantified as a function of F(- dose and pH. Luciferase secretion significantly decreased within 2 hr of F(- treatment at low pH versus neutral pH, indicating increased functional toxicity. Rats given 100 ppm F(- in their drinking water exhibited increased stress-mediated phosphorylation of eIF2alpha in maturation stage ameloblasts (pH<6.0 as compared to secretory stage ameloblasts (pH approximately 7.2. Intriguingly, F(--treated rats demonstrated a striking decrease in transcripts expressed during the maturation stage of enamel development (Klk4 and Amtn. In contrast, the expression of secretory stage genes, AmelX, Ambn, Enam and Mmp20, was unaffected.The low pH environment of maturation stage ameloblasts facilitates the uptake of F(-, causing increased cell stress that compromises ameloblast function, resulting in dental fluorosis.

  18. The acid test of fluoride: how pH modulates toxicity.

    Science.gov (United States)

    Sharma, Ramaswamy; Tsuchiya, Masahiro; Skobe, Ziedonis; Tannous, Bakhos A; Bartlett, John D

    2010-05-28

    It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F(-)). Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of F(-). Enamel formation is initiated in a neutral pH environment (secretory stage); however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage). Low pH can facilitate entry of F(-) into cells. Here, we asked if F(-) was more toxic at low pH, as measured by increased cell stress and decreased cell function. Treatment of ameloblast-derived LS8 cells with F(-) at low pH reduced the threshold dose of F(-) required to phosphorylate stress-related proteins, PERK, eIF2alpha, JNK and c-jun. To assess protein secretion, LS8 cells were stably transduced with a secreted reporter, Gaussia luciferase, and secretion was quantified as a function of F(-) dose and pH. Luciferase secretion significantly decreased within 2 hr of F(-) treatment at low pH versus neutral pH, indicating increased functional toxicity. Rats given 100 ppm F(-) in their drinking water exhibited increased stress-mediated phosphorylation of eIF2alpha in maturation stage ameloblasts (pHdental fluorosis.

  19. Electroosmosis modulated biomechanical transport through asymmetric microfluidics channel

    Science.gov (United States)

    Jhorar, R.; Tripathi, D.; Bhatti, M. M.; Ellahi, R.

    2018-05-01

    This article addresses the electrokinetically modulated biomechanical transport through a two-dimensional asymmetric microchannel induced by peristaltic waves. Electrokinetic transport with peristaltic phenomena grabbed a significant attention due to its novel applications in engineering. Electrical fields also provide an excellent mode for regulating flows. The electrohydrodynamics problem is modified by means of Debye-Hückel linearization. Firstly, the governing flow problem is described by continuity and momentum equations in the presence of electrokinetic forces in Cartesian coordinates, then long wavelength and low/zero Reynolds ("neglecting the inertial forces") approximations are applied to modify the governing flow problem. The resulting differential equations are solved analytically in order to obtain exact solutions for velocity profile whereas the numerical integration is carried out to analyze the pumping characteristics. The physical behaviour of sundry parameters is discussed for velocity profile, pressure rise and volume flow rate. In particular, the behaviour of electro-osmotic parameter, phase difference, and Helmholtz-Smoluchowski velocity is examined and discussed. The trapping mechanism is also visualized by drawing streamlines against the governing parameters. The present study offers various interesting results that warrant further study on electrokinetic transport with peristalsis.

  20. Transport phenomena in high Tc superconductors. Resume of Ph.D thesis

    International Nuclear Information System (INIS)

    Crisan, I.A.

    1994-01-01

    This is an extended abstract of the Ph. D. thesis devoted to the transport phenomena in high-Tc superconductors. There are three chapters. The first chapter presents an overview of the essential theoretical aspects concerning the vortex dynamics particularly in ceramic superconductors. The chapter two gives a description of the preparation methods of superconductor samples used by the author as well as the measurement devices for volt-ampere characteristics and the associated electronic circuitry. In the third chapter there are presented the experimental data obtained from different samples prepared in different temperature and magnetic field conditions. The obtained results are finally interpreted in the frame of existent or original models. (M.I.C.). 31 Refs

  1. Rationally Engineering Phototherapy Modules of Eosin-Conjugated Responsive Polymeric Nanocarriers via Intracellular Endocytic pH Gradients.

    Science.gov (United States)

    Liu, Guhuan; Hu, Jinming; Zhang, Guoying; Liu, Shiyong

    2015-07-15

    Spatiotemporal switching of respective phototherapy modes at the cellular level with minimum side effects and high therapeutic efficacy is a major challenge for cancer phototherapy. Herein we demonstrate how to address this issue by employing photosensitizer-conjugated pH-responsive block copolymers in combination with intracellular endocytic pH gradients. At neutral pH corresponding to extracellular and cytosol milieu, the copolymers self-assemble into micelles with prominently quenched fluorescence emission and low (1)O2 generation capability, favoring a highly efficient photothermal module. Under mildly acidic pH associated with endolysosomes, protonation-triggered micelle-to-unimer transition results in recovered emission and enhanced photodynamic (1)O2 efficiency, which synergistically actuates release of encapsulated drugs, endosomal escape, and photochemical internalization processes.

  2. Extracellular pH Modulates Neuroendocrine Prostate Cancer Cell Metabolism and Susceptibility to the Mitochondrial Inhibitor Niclosamide

    Science.gov (United States)

    Ippolito, Joseph E.; Brandenburg, Matthew W.; Ge, Xia; Crowley, Jan R.; Kirmess, Kristopher M.; Som, Avik; D’Avignon, D. Andre; Arbeit, Jeffrey M.; Achilefu, Samuel; Yarasheski, Kevin E.; Milbrandt, Jeffrey

    2016-01-01

    Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6.5, 7.4, and 8.5) on neuroendocrine prostate cancer cell metabolism. We discovered that alkalinization of extracellular pH converted cellular metabolism to a nutrient consumption-dependent state that was susceptible to glucose deprivation, glutamine deprivation, and 2-deoxyglucose (2-DG) mediated inhibition of glycolysis. Conversely, acidic pH shifted cellular metabolism toward an oxidative phosphorylation (OXPHOS)-dependent state that was susceptible to OXPHOS inhibition. Based upon this mechanistic knowledge of pH-dependent metabolism, we identified that the FDA-approved anti-helminthic niclosamide depolarized mitochondrial potential and depleted ATP levels in PNEC cells whose effects were enhanced in acidic pH. To further establish relevance of these findings, we tested the effects of extracellular pH on susceptibility to nutrient deprivation and OXPHOS inhibition in a cohort of castrate-resistant prostate cancer cell lines C4-2B, PC-3, and PC-3M. We discovered similar pH-dependent toxicity profiles among all cell lines with these treatments. These findings underscore a potential importance to acidic extracellular pH in the modulation of cell metabolism in tumors and development of an emerging paradigm that exploits the synergy of environment and therapeutic efficacy in cancer. PMID:27438712

  3. Steviol Glycosides Modulate Glucose Transport in Different Cell Types

    Science.gov (United States)

    Rizzo, Benedetta; Zambonin, Laura; Leoncini, Emanuela; Vieceli Dalla Sega, Francesco; Prata, Cecilia; Fiorentini, Diana; Hrelia, Silvana

    2013-01-01

    Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway. PMID:24327825

  4. Two rhodamine lactam modulated lysosome-targetable fluorescence probes for sensitively and selectively monitoring subcellular organelle pH change

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hongmei [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Wang, Cuiling [Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi' an 710069 (China); She, Mengyao; Zhu, Yuelu; Zhang, Jidong; Yang, Zheng [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Liu, Ping, E-mail: liuping@nwu.edu.cn [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Wang, Yaoyu [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Li, Jianli, E-mail: lijianli@nwu.edu.cn [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China)

    2015-11-05

    Be a powerful technique for convenient detection of pH change in living cells, especially at subcellular level, fluorescent probes has attracted more and more attention. In this work, we designed and synthesized three rhodamine lactam modulated fluorescent probes RS1, RS2 and RS3, which all respond sensitively toward weak acidity (pH range 4–6) via the photophysical property in buffer solution without interference from the other metal ions, and they also show ideal pKa values and excellent reversibility. Particularly, by changing the lone pair electrons distribution of lactam-N atom with different conjugations, RS2 and RS3 exhibit high quantum yield, negligible cytotoxicity and excellent permeability. They are suitable to stain selectively lysosomes of tumor cells and monitor its pH changes sensitively via optical molecular imaging. The above findings suggest that the probes we designed could act as ideal and easy method for investigating the pivotal role of H{sup +} in lysosomes and are potential pH detectors in disease diagnosis through direct intracellular imaging. - Highlights: • Two probes for sensitively and selectively monitoring weak acidic pH change. • The pKa of the probes was highly suitable for staining lysosomes in tumor cells. • The properties of those probes were changed by different conjugate system. • These probes have negligible cytotoxicity and good sensitivity in vivo.

  5. Two rhodamine lactam modulated lysosome-targetable fluorescence probes for sensitively and selectively monitoring subcellular organelle pH change

    International Nuclear Information System (INIS)

    Li, Hongmei; Wang, Cuiling; She, Mengyao; Zhu, Yuelu; Zhang, Jidong; Yang, Zheng; Liu, Ping; Wang, Yaoyu; Li, Jianli

    2015-01-01

    Be a powerful technique for convenient detection of pH change in living cells, especially at subcellular level, fluorescent probes has attracted more and more attention. In this work, we designed and synthesized three rhodamine lactam modulated fluorescent probes RS1, RS2 and RS3, which all respond sensitively toward weak acidity (pH range 4–6) via the photophysical property in buffer solution without interference from the other metal ions, and they also show ideal pKa values and excellent reversibility. Particularly, by changing the lone pair electrons distribution of lactam-N atom with different conjugations, RS2 and RS3 exhibit high quantum yield, negligible cytotoxicity and excellent permeability. They are suitable to stain selectively lysosomes of tumor cells and monitor its pH changes sensitively via optical molecular imaging. The above findings suggest that the probes we designed could act as ideal and easy method for investigating the pivotal role of H + in lysosomes and are potential pH detectors in disease diagnosis through direct intracellular imaging. - Highlights: • Two probes for sensitively and selectively monitoring weak acidic pH change. • The pKa of the probes was highly suitable for staining lysosomes in tumor cells. • The properties of those probes were changed by different conjugate system. • These probes have negligible cytotoxicity and good sensitivity in vivo.

  6. Influence of pH on the transport of silver nanoparticles in saturated porous media: laboratory experiments and modeling

    Energy Technology Data Exchange (ETDEWEB)

    Flory, Jason; Kanel, Sushil R., E-mail: sushil.kanel.ctr@afit.edu; Racz, LeeAnn [Air Force Institute of Technology, Department of Systems and Engineering Management (United States); Impellitteri, Christopher A. [U.S. Environmental Protection Agency (United States); Silva, Rendahandi G. [U.S. EPA Test and Evaluation Facility, National Risk Management Research Laboratory, U.S. Environmental Protection Agency, Shaw Environmental and Infrastructure (United States); Goltz, Mark N., E-mail: mark.goltz@afit.edu [Air Force Institute of Technology, Department of Systems and Engineering Management (United States)

    2013-03-15

    Given the ubiquity of silver nanoparticles (AgNPs) and their potential for toxic effects on both humans and the environment, it is important to understand their environmental fate and transport. The purpose of this study is to gain information on the transport properties of commercial AgNP suspensions in a glass bead-packed column under saturated flow conditions at different solution pH levels. Commercial AgNPs were characterized using high-resolution transmission electron microscopy, dynamic light scattering, X-ray photoelectron spectroscopy, ultraviolet visible spectroscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction. Transport data were collected at different pH levels (4, 6.5, 9, and 11) at fixed ionic strength. Capture of AgNPs increased as the pH of the solution increased from 4 to 6.5. Further increase in pH to 9 and 11 decreased the attachment of AgNPs to the glass beads. AgNP concentration versus time breakthrough data were simulated using an advection-dispersion model incorporating both irreversible and reversible attachment. In particular, a reversible attachment model is required to simulate breakthrough curve tailing at near neutral pH, when attachment is most significant. The laboratory and modeling study reveals that for natural groundwaters, AgNP transport in porous media may be retarded due to capture; but ultimately, most of the mass may be slowly released over time.

  7. Arginine Improves pH Homeostasis via Metabolism and Microbiome Modulation.

    Science.gov (United States)

    Agnello, M; Cen, L; Tran, N C; Shi, W; McLean, J S; He, X

    2017-07-01

    Dental caries can be described as a dysbiosis of the oral microbial community, in which acidogenic, aciduric, and acid-adapted bacterial species promote a pathogenic environment, leading to demineralization. Alkali generation by oral microbes, specifically via arginine catabolic pathways, is an essential factor in maintaining plaque pH homeostasis. There is evidence that the use of arginine in dentifrices helps protect against caries. The aim of the current study was to investigate the mechanistic and ecological effect of arginine treatment on the oral microbiome and its regulation of pH dynamics, using an in vitro multispecies oral biofilm model that was previously shown to be highly reflective of the in vivo oral microbiome. Pooled saliva from 6 healthy subjects was used to generate overnight biofilms, reflecting early stages of biofilm maturation. First, we investigated the uptake of arginine by the cells of the biofilm as well as the metabolites generated. We next explored the effect of arginine on pH dynamics by pretreating biofilms with 75 mM arginine, followed by the addition of sucrose (15 mM) after 0, 6, 20, or 48 h. pH was measured at each time point and biofilms were collected for 16S sequencing and targeted arginine quantification, and supernatants were prepared for metabolomic analysis. Treatment with only sucrose led to a sustained pH drop from 7 to 4.5, while biofilms treated with sucrose after 6, 20, or 48 h of preincubation with arginine exhibited a recovery to higher pH. Arginine was detected within the cells of the biofilms, indicating active uptake, and arginine catabolites citrulline, ornithine, and putrescine were detected in supernatants, indicating active metabolism. Sequencing analysis revealed a shift in the microbial community structure in arginine-treated biofilms as well as increased species diversity. Overall, we show that arginine improved pH homeostasis through a remodeling of the oral microbial community.

  8. pH- and temperature-sensitive polymeric microspheres for drug delivery: the dissolution of copolymers modulates drug release.

    Science.gov (United States)

    Fundueanu, Gheorghe; Constantin, Marieta; Stanciu, Cristina; Theodoridis, Georgios; Ascenzi, Paolo

    2009-12-01

    Most pH-/temperature-responsive polymers for controlled release of drugs are used as cross-linked hydrogels. However, the solubility properties of the linear polymers below and above the lower critical solution temperature (LCST) are not exploited. Here, the preparation and characterization of poly (N-isopropylacrylamide-co-methacrylic acid-co-methyl methacrylate) (poly (NIPAAm-co-MA-co-MM)) and poly (N-isopropylacrylamide-co-acrylamide) (poly (NIPAAm-co-AAm)), known as "smart" polymers (SP), is reported. Both poly (NIPAAm-co-MA-co-MM) and poly (NIPAAm-co-AAm) display pH- and temperature-responsive properties. Poly (NIPAAm-co-MA-co-MM) was designed to be insoluble in the gastric fluid (pH = 1.2), but soluble in the intestinal fluid (pH = 6.8 and 7.4), at the body temperature (37 degrees C). Poly (NIPAAm-co-AAm) was designed to have a lower critical solution temperature (LCST) corresponding to 37 degrees C at pH = 7.4, therefore it is not soluble above the LCST. The solubility characteristics of these copolymers were exploited to modulate the rate of release of drugs by changing pH and/or temperature. These copolymers were solubilized with hydrophobic cellulose acetate butyrate (CAB) and vitamin B(12) (taken as a water soluble drug model system) in an acetone/methanol mixture and dispersed in mineral oil. By a progressive evaporation of the solvent, the liquid droplets were transformed into loaded CAB/SP microspheres. Differential scanning calorimetric studies and scanning electron microscopy analysis demonstrated that the polymeric components of the microspheres precipitated separately during solvent evaporation forming small microdomains. Moreover, vitamin B(12) was found to be molecularly dispersed in both microdomains with no specific affinity for any polymeric component of microspheres. The release of vitamin B(12) was investigated as a function of temperature, pH, and the CAB/SP ratio.

  9. Medium pH in submerged cultivation modulates differences in the intracellular protein profile of Fusarium oxysporum.

    Science.gov (United States)

    da Rosa-Garzon, Nathália Gonsales; Laure, Hélen Julie; Souza-Motta, Cristina Maria de; Rosa, José César; Cabral, Hamilton

    2017-08-09

    Fusarium oxysporum is a filamentous fungus that damages a wide range of plants and thus causes severe crop losses. In fungal pathogens, the genes and proteins involved in virulence are known to be controlled by environmental pH. Here, we report the influence of culture-medium pH (5, 6, 7, and 8) on the production of degradative enzymes involved in the pathogenesis of F. oxysporum URM 7401 and on the 2D-electrophoresis profile of intracellular proteins in this fungus. F. oxysporum URM 7401 was grown in acidic, neutral, and alkaline culture media in a submerged bioprocess. After 96 hr, the crude extract was processed to enzyme activity assays, while the intracellular proteins were obtained from mycelium and analyzed using 2D electrophoresis and mass spectrometry. We note that the diversity of secreted enzymes was changed quantitatively in different culture-medium pH. Also, the highest accumulated biomass and the intracellular protein profile of F. oxysporum URM 7401 indicate an increase in metabolism in neutral-alkaline conditions. The differential profiles of secreted enzymes and intracellular proteins under the evaluated conditions indicate that the global protein content in F. oxysporum URM 7401 is modulated by extracellular pH.

  10. Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke.

    Science.gov (United States)

    Li, Ming-Hua; Leng, Tian-Dong; Feng, Xue-Chao; Yang, Tao; Simon, Roger P; Xiong, Zhi-Gang

    2016-08-26

    An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis. Our previous studies show that acidosis-induced cell injury in in vitro models is attenuated by intracellular acidification. However, whether pHi affects ischemic brain injury in vivo is completely unknown. Furthermore, whereas ASICs in native neurons are composed of different subunits characterized by distinct electrophysiological/pharmacological properties, the subunit-dependent modulation of ASIC activity by pHi has not been investigated. Using a combination of in vitro and in vivo ischemic brain injury models, electrophysiological, biochemical, and molecular biological approaches, we show that the intracellular alkalizing agent quinine potentiates, whereas the intracellular acidifying agent propionate inhibits, oxygen-glucose deprivation-induced cell injury in vitro and brain ischemia-induced infarct volume in vivo Moreover, we find that the potentiation of ASICs by quinine depends on the presence of the ASIC1a, ASIC2a subunits, but not ASIC1b, ASIC3 subunits. Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Modulation of Connexin-36 Gap Junction Channels by Intracellular pH and Magnesium Ions.

    Science.gov (United States)

    Rimkute, Lina; Kraujalis, Tadas; Snipas, Mindaugas; Palacios-Prado, Nicolas; Jotautis, Vaidas; Skeberdis, Vytenis A; Bukauskas, Feliksas F

    2018-01-01

    Connexin-36 (Cx36) protein forms gap junction (GJ) channels in pancreatic beta cells and is also the main Cx isoform forming electrical synapses in the adult mammalian brain. Cx36 GJs can be regulated by intracellular pH (pH i ) and cytosolic magnesium ion concentration ([Mg 2+ ] i ), which can vary significantly under various physiological and pathological conditions. However, the combined effect and relationship of these two factors over Cx36-dependent coupling have not been previously studied in detail. Our experimental results in HeLa cells expressing Cx36 show that changes in both pH i and [Mg 2+ ] i affect junctional conductance (g j ) in an interdependent manner; in other words, intracellular acidification cause increase or decay in g j depending on whether [Mg 2+ ] i is high or low, respectively, and intracellular alkalization cause reduction in g j independently of [Mg 2+ ] i . Our experimental and modelling data support the hypothesis that Cx36 GJ channels contain two separate gating mechanisms, and both are differentially sensitive to changes in pH i and [Mg 2+ ] i . Using recombinant Cx36 we found that two glutamate residues in the N-terminus could be partly responsible for the observed interrelated effect of pH i and [Mg 2+ ] i . Mutation of glutamate at position 8 attenuated the stimulatory effect of intracellular acidification at high [Mg 2+ ] i , while mutation at position 12 and double mutation at both positions reversed stimulatory effect to inhibition. Moreover, Cx36 * E8Q lost the initial increase of g j at low [Mg 2+ ] i and double mutation lost the sensitivity to high [Mg 2+ ] i . These results suggest that E8 and E12 are involved in regulation of Cx36 GJ channels by Mg 2+ and H + ions.

  12. Transporting the last superconducting module to be removed from LEP

    CERN Multimedia

    Patrice Loïez

    2001-01-01

    All 72 of LEP's superconducting modules have now been raised to the surface. Some 80% will be preserved at CERN, with 10% being reused for the LHC and a further 10% of obsolete non-radioactive material destined for recycling. These pictures show the last of these modules on its journey from PM18 to the old ISR tunnel where the modules will be stored in the short term. Photo 01: The Ansaldo 1020 module leaves PM18 by lorry. Photo 03: The module on the SM18 site. Photos 06, 08: The module on the road.

  13. Transport of vanadium (V in saturated porous media: effects of pH, ionic-strength and clay mineral

    Directory of Open Access Journals (Sweden)

    Yulu Wang

    2016-10-01

    Full Text Available Vanadium, a hazardous pollutant, has been frequently detected in soil and groundwater, however, its transport behavior in porous media were not clearly understood. In this study, the effects of solution pH, ionic strength (IS and the effect of clay mineral on the transport of vanadium in saturated porous media were investigated. Laboratory experiments using a series of columns packed with quartz sand were carried out to explore the retention and transport of vanadium with a range of ionic-strength (0.001–0.1 M and pH (4–8 and two different types of clay minerals montmorillonite and kaolinite. Results of the breakthrough experiments showed that vanadium was highly mobile in the saturated porous media. The increase in pH rendered a higher transport of vanadium in saturated porous media. The study also indicated an easier transfer of vanadium with an increase in IS. Montmorillonite enhanced the mobility of vanadium in the column when compared to kaolinite. A mathematical model based on advection-dispersion equation coupled with equilibrium and kinetic reactions was used to describe the retention and transport of vanadium in the columns very well.

  14. Modulation of ion transport across rat distal colon by cysteine

    Directory of Open Access Journals (Sweden)

    Martin eDiener

    2012-03-01

    Full Text Available The aim of this study was to identify the actions of stimulation of endogenous production of H2S by cysteine, the substrate for the two H2S-producing enzymes, cystathionin-beta-synthase and cystathionin-gamma-lyase, on ion transport across rat distal colon. Changes in short-circuit current (Isc induced by cysteine were measured in Ussing chambers. Free cysteine caused a concentration-dependent, transient fall in Isc, which was sensitive to amino-oxyacetate and beta-cyano-L-alanine, i.e. inhibitors of H2S-producing enzymes. In contrast, Na cysteinate evoked a biphasic change in Isc, i.e. an initial fall followed by a secondary increase, which was also reduced by these enzyme inhibitors. All responses were dependent on the presence of Cl- and inhibited by bumetanide, suggesting that free cysteine induces an inhibition of transcellular Cl- secretion, whereas Na cysteinate – after a transient inhibitory phase – activates anion secretion. The assumed reason for this discrepancy is a fall in the cytosolic pH induced by free cysteine, but not by Na cysteinate, as observed in isolated colonic crypts loaded with the pH-sensitive dye, BCECF. Intracellular acidification is known to inhibit epithelial K+ channels. Indeed, after preinhibition of basolateral K+ channels with tetrapentylammonium or Ba2+, the negative Isc induced by free cysteine was reduced significantly. In consequence, stimulation of endogenous H2S production by Na cysteinate causes, after a short inhibitory response, a delayed activation of anion secretion, which is missing in the case of free cysteine, probably due to the cytosolic acidification. In contrast, diallyl trisulfide, which is intracellularly converted to H2S, only evoked a monophasic increase in Isc without the initial fall observed with Na cysteinate. Consequently, time course and amount of produced H2S seem to strongly influence the functional response of the colonic epithelium evoked by this gasotransmitter.

  15. Ethylene regulates phosphorus remobilization and expression of a phosphate transporter (PhPT1) during petunia corolla senescence

    Science.gov (United States)

    Chapin, Laura J.; Jones, Michelle L.

    2009-01-01

    The programmed degradation of macromolecules during petal senescence allows the plant to remobilize nutrients from dying to developing tissues. Ethylene is involved in regulating the timing of nucleic acid degradation in petunia, but it is not clear if ethylene has a role in the remobilization of phosphorus during petal senescence. To investigate ethylene's role in nutrient remobilization, the P content of petals (collectively called the corolla) during early development and senescence was compared in ethylene-sensitive wild type Petunia×hybrida ‘Mitchell Diploid’ (MD) and transgenic petunias with reduced sensitivity to ethylene (35S::etr1-1). When compared to the total P content of corollas on the day of flower opening (the early non-senescing stage), P in MD corollas had decreased 74% by the late stage of senescence (advanced wilting). By contrast, P levels were only reduced by an average of 32% during etr1-1 corolla (lines 44568 and Z00-35-10) senescence. A high-affinity phosphate transporter, PhPT1 (PhPht1;1), was cloned from senescing petunia corollas by RT-PCR. PhPT1 expression was up-regulated during MD corolla senescence and a much smaller increase was detected during the senescence of etr1-1 petunia corollas. PhPT1 mRNA levels showed a rapid increase in detached corollas (treated at 1 d after flower opening) following treatment with low levels of ethylene (0.1 μl l-1). Transcripts accumulated in the presence of the protein synthesis inhibitor, cycloheximide, indicating that PhPT1 is a primary ethylene response gene. PhPT1 is a putative phosphate transporter that may function in Pi translocation during senescence. PMID:19380421

  16. How pH Modulates the Reactivity and Selectivity of a Siderophore-Associated Flavin Monooxygenase

    Science.gov (United States)

    2015-01-01

    Flavin-containing monooxygenases (FMOs) catalyze the oxygenation of diverse organic molecules using O2, NADPH, and the flavin adenine dinucleotide (FAD) cofactor. The fungal FMO SidA initiates peptidic siderophore biosynthesis via the highly selective hydroxylation of l-ornithine, while the related amino acid l-lysine is a potent effector of reaction uncoupling to generate H2O2. We hypothesized that protonation states could critically influence both substrate-selective hydroxylation and H2O2 release, and therefore undertook a study of SidA’s pH-dependent reaction kinetics. Consistent with other FMOs that stabilize a C4a-OO(H) intermediate, SidA’s reductive half reaction is pH independent. The rate constant for the formation of the reactive C4a-OO(H) intermediate from reduced SidA and O2 is likewise independent of pH. However, the rate constants for C4a-OO(H) reactions, either to eliminate H2O2 or to hydroxylate l-Orn, were strongly pH-dependent and influenced by the nature of the bound amino acid. Solvent kinetic isotope effects of 6.6 ± 0.3 and 1.9 ± 0.2 were measured for the C4a-OOH/H2O2 conversion in the presence and absence of l-Lys, respectively. A model is proposed in which l-Lys accelerates H2O2 release via an acid–base mechanism and where side-chain position determines whether H2O2 or the hydroxylation product is observed. PMID:24490904

  17. Operation, analysis, and design of signalized intersections : a module for the introductory course in transportation engineering.

    Science.gov (United States)

    2014-02-01

    This report presents materials that can be used as the basis for a module on signalized intersections in the introductory : course in transportation engineering. The materials were developed based on studies of the work of students who took : this in...

  18. Automated Transportation Management System (ATMS) V2.0 logistics module PBI acceptance criteria

    International Nuclear Information System (INIS)

    Weidert, R.S.

    1995-01-01

    This document defines the acceptance criteria for the Automated Transportation Management System V2.0 Logistics Module Performance Based Incentive (PBI). This acceptance criteria will be the primary basis for the generation of acceptance test procedures. The purpose of this document is to define the minimum criteria that must be fulfilled to guarantee acceptance of the Logistics Module

  19. Modulating β-lactoglobulin nanofibril self-assembly at pH 2 using glycerol and sorbitol.

    Science.gov (United States)

    Dave, Anant C; Loveday, Simon M; Anema, Skelte G; Jameson, Geoffrey B; Singh, Harjinder

    2014-01-13

    β-Lactoglobulin (β-lg) forms fibrils when heated at 80 °C, pH 2, and low ionic strength (sorbitol (0-50% w/v) on β-lg self-assembly at pH 2. Glycerol and sorbitol stabilize native protein structure and modulate protein functionality by preferential exclusion. In our study, both polyols decreased the rate of β-lg self-assembly but had no effect on the morphology of fibrils. The mechanism of these effects was studied using circular dichroism spectroscopy and SDS-PAGE. Sorbitol inhibited self-assembly by stabilizing β-lg against unfolding and hydrolysis, resulting in fewer fibrillogenic species, whereas glycerol inhibited nucleation without inhibiting hydrolysis. Both polyols increased the viscosity of the solutions, but viscosity appeared to have little effect on fibril assembly, and we believe that self-assembly was not diffusion-limited under these conditions. This is in agreement with previous reports for other proteins assembling under different conditions. The phenomenon of peptide self-assembly can be decoupled from protein hydrolysis using glycerol.

  20. Identification of Candida glabrata genes involved in pH modulation and modification of the phagosomal environment in macrophages.

    Directory of Open Access Journals (Sweden)

    Lydia Kasper

    Full Text Available Candida glabrata currently ranks as the second most frequent cause of invasive candidiasis. Our previous work has shown that C. glabrata is adapted to intracellular survival in macrophages and replicates within non-acidified late endosomal-stage phagosomes. In contrast, heat killed yeasts are found in acidified matured phagosomes. In the present study, we aimed at elucidating the processes leading to inhibition of phagosome acidification and maturation. We show that phagosomes containing viable C. glabrata cells do not fuse with pre-labeled lysosomes and possess low phagosomal hydrolase activity. Inhibition of acidification occurs independent of macrophage type (human/murine, differentiation (M1-/M2-type or activation status (vitamin D3 stimulation. We observed no differential activation of macrophage MAPK or NFκB signaling cascades downstream of pattern recognition receptors after internalization of viable compared to heat killed yeasts, but Syk activation decayed faster in macrophages containing viable yeasts. Thus, delivery of viable yeasts to non-matured phagosomes is likely not triggered by initial recognition events via MAPK or NFκB signaling, but Syk activation may be involved. Although V-ATPase is abundant in C. glabrata phagosomes, the influence of this proton pump on intracellular survival is low since blocking V-ATPase activity with bafilomycin A1 has no influence on fungal viability. Active pH modulation is one possible fungal strategy to change phagosome pH. In fact, C. glabrata is able to alkalinize its extracellular environment, when growing on amino acids as the sole carbon source in vitro. By screening a C. glabrata mutant library we identified genes important for environmental alkalinization that were further tested for their impact on phagosome pH. We found that the lack of fungal mannosyltransferases resulted in severely reduced alkalinization in vitro and in the delivery of C. glabrata to acidified phagosomes. Therefore

  1. Muscle pH, rigor mortis and blood variables in Atlantic salmon transported in two types of well-boat.

    Science.gov (United States)

    Gatica, M C; Monti, G E; Knowles, T G; Gallo, C B

    2010-01-09

    Two systems for transporting live salmon (Salmo salar) were compared in terms of their effects on blood variables, muscle pH and rigor index: an 'open system' well-boat with recirculated sea water at 13.5 degrees C and a stocking density of 107 kg/m3 during an eight-hour journey, and a 'closed system' well-boat with water chilled from 16.7 to 2.1 degrees C and a stocking density of 243.7 kg/m3 during a seven-hour journey. Groups of 10 fish were sampled at each of four stages: in cages at the farm, in the well-boat after loading, in the well-boat after the journey and before unloading, and in the processing plant after they were pumped from the resting cages. At each sampling, the fish were stunned and bled by gill cutting. Blood samples were taken to measure lactate, osmolality, chloride, sodium, cortisol and glucose, and their muscle pH and rigor index were measured at death and three hours later. In the open system well-boat, the initial muscle pH of the fish decreased at each successive stage, and at the final stage they had a significantly lower initial muscle pH and more rapid onset of rigor than the fish transported on the closed system well-boat. At the final stage all the blood variables except glucose were significantly affected in the fish transported on both types of well-boat.

  2. High pressure modulated transport and signaling functions of membrane proteins in models and in vivo

    International Nuclear Information System (INIS)

    Vogel, R F; Linke, K; Teichert, H; Ehrmann, M A

    2008-01-01

    Cellular membranes serve in the separation of compartments, recognition of the environment, selective transport and signal transduction. Membrane lipids and membrane proteins play distinct roles in these processes, which are affected by environmental chemical (e. g. pH) or physical (e. g. pressure and temperature) changes. High hydrostatic pressure (HHP) affects fluidity and integrity of bacterial membranes instantly during the ramp, resulting in a loss of membrane potential and vital membrane protein functions. We have used the multiple drug transporter LmrA from Lactococcus lactis and ToxR, a membrane protein sensor from Photobacterium profundum, a deep-sea bacterium, and Vibrio cholerae to study membrane protein interaction and functionality in proteolioposomes and by the use of in vivo reporter systems, respectively. Both proteins require dimerization in the phospholipid bilayer for their functionality, which was favoured in the liquid crystalline lipid phase with ToxR and LmrA. Whereas LmrA, which resides in liposomes consisting of DMPC, DMPC/cholesterol or natural lipids, lost its ATPase activity above 20 or 40 MPa, it maintained its active dimeric structure in DOPC/DPPC/cholesterol liposomes up to 120 MPa. By using a specific indicator strain in which the dimerisation of ToxR initiates the transcription of lacZ it was demonstrated, that the amino acid sequence of the transmembrane domain influences HHP stability of ToxR dimerization in vivo. Thus, both the lipid structure and the nature of the protein affect membrane protein interaction. It is suggested that the protein structure determines basic functionality, e.g. principle ability or kinetics to dimerize to a functional complex, while the lipid environment modulates this property

  3. High pressure modulated transport and signaling functions of membrane proteins in models and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, R F; Linke, K; Teichert, H; Ehrmann, M A [Technische Universitaet Muenchen, Technische Mikrobiologie, Weihenstephaner Steig 16, 85350 Freising (Germany)], E-mail: rudi.vogel@wzw.tum.de

    2008-07-15

    Cellular membranes serve in the separation of compartments, recognition of the environment, selective transport and signal transduction. Membrane lipids and membrane proteins play distinct roles in these processes, which are affected by environmental chemical (e. g. pH) or physical (e. g. pressure and temperature) changes. High hydrostatic pressure (HHP) affects fluidity and integrity of bacterial membranes instantly during the ramp, resulting in a loss of membrane potential and vital membrane protein functions. We have used the multiple drug transporter LmrA from Lactococcus lactis and ToxR, a membrane protein sensor from Photobacterium profundum, a deep-sea bacterium, and Vibrio cholerae to study membrane protein interaction and functionality in proteolioposomes and by the use of in vivo reporter systems, respectively. Both proteins require dimerization in the phospholipid bilayer for their functionality, which was favoured in the liquid crystalline lipid phase with ToxR and LmrA. Whereas LmrA, which resides in liposomes consisting of DMPC, DMPC/cholesterol or natural lipids, lost its ATPase activity above 20 or 40 MPa, it maintained its active dimeric structure in DOPC/DPPC/cholesterol liposomes up to 120 MPa. By using a specific indicator strain in which the dimerisation of ToxR initiates the transcription of lacZ it was demonstrated, that the amino acid sequence of the transmembrane domain influences HHP stability of ToxR dimerization in vivo. Thus, both the lipid structure and the nature of the protein affect membrane protein interaction. It is suggested that the protein structure determines basic functionality, e.g. principle ability or kinetics to dimerize to a functional complex, while the lipid environment modulates this property.

  4. High pressure modulated transport and signaling functions of membrane proteins in models and in vivo

    Science.gov (United States)

    Vogel, R. F.; Linke, K.; Teichert, H.; Ehrmann, M. A.

    2008-07-01

    Cellular membranes serve in the separation of compartments, recognition of the environment, selective transport and signal transduction. Membrane lipids and membrane proteins play distinct roles in these processes, which are affected by environmental chemical (e. g. pH) or physical (e. g. pressure and temperature) changes. High hydrostatic pressure (HHP) affects fluidity and integrity of bacterial membranes instantly during the ramp, resulting in a loss of membrane potential and vital membrane protein functions. We have used the multiple drug transporter LmrA from Lactococcus lactis and ToxR, a membrane protein sensor from Photobacterium profundum, a deep-sea bacterium, and Vibrio cholerae to study membrane protein interaction and functionality in proteolioposomes and by the use of in vivo reporter systems, respectively. Both proteins require dimerization in the phospholipid bilayer for their functionality, which was favoured in the liquid crystalline lipid phase with ToxR and LmrA. Whereas LmrA, which resides in liposomes consisting of DMPC, DMPC/cholesterol or natural lipids, lost its ATPase activity above 20 or 40 MPa, it maintained its active dimeric structure in DOPC/DPPC/cholesterol liposomes up to 120 MPa. By using a specific indicator strain in which the dimerisation of ToxR initiates the transcription of lacZ it was demonstrated, that the amino acid sequence of the transmembrane domain influences HHP stability of ToxR dimerization in vivo. Thus, both the lipid structure and the nature of the protein affect membrane protein interaction. It is suggested that the protein structure determines basic functionality, e.g. principle ability or kinetics to dimerize to a functional complex, while the lipid environment modulates this property.

  5. Urban Environmental Education Project, Curriculum Module III: Urban Transportation - Where Are We Going?

    Science.gov (United States)

    Bell, Ellen

    Included in this module are five activities dealing with modes of transportation in the urban environment. The activities include: (1) a discussion of transportation considerations in urban areas; (2) discussion of bikeways and their desirability in the urban environment; (3) the bikeway and the environment; (4) designing a bikeway; and (5)…

  6. Effects of well-boat transportation on the muscle pH and onset of rigor mortis in Atlantic salmon.

    Science.gov (United States)

    Gatica, M C; Monti, G; Gallo, C; Knowles, T G; Warriss, P D

    2008-07-26

    During the transport of salmon (Salmo salar), in a well-boat, 10 fish were sampled at each of six stages: in cages after crowding at the farm (stage 1), in the well-boat after loading (stage 2), in the well-boat after eight hours transport and before unloading (stage 3), in the resting cages immediately after finishing unloading (stage 4), after 24 hours resting in cages, (stage 5) and in the processing plant after pumping from the resting cages (stage 6). The water in the well-boat was at ambient temperature with recirculation to the sea. At each stage the fish were stunned percussively and bled by gill cutting. Immediately after death, and then every three hours for 18 hours, the muscle pH and rigor index of the fish were measured. At successive stages the initial muscle pH of the fish decreased, except for a slight gain in stage 5, after they had been rested for 24 hours. The lowest initial muscle pH was observed at stage 6. The fishes' rigor index showed that rigor developed more quickly at each successive stage, except for a slight decrease in rate at stage 5, attributable to the recovery of muscle reserves.

  7. Influence Of pH On The Transport Of Nanoscale Zinc Oxide In Saturated Porous Media

    Science.gov (United States)

    Widespread use of nanoscale zinc oxide (nZnO) in various fields causes subsurface environment contamination. Even though the transport of dissolved zinc ions in subsurface environments such as soils and sediments has been widely studied, the transport mechanism of nZnO in such e...

  8. Majorana fermion modulated nonequilibrium transport through double quantum dots

    International Nuclear Information System (INIS)

    Deng, Ming-Xun; Wang, Rui-Qiang; Ai, Bao-Quan; Yang, Mou; Hu, Liang-Bin; Zhong, Qing-Hu; Wang, Guang-Hui

    2014-01-01

    Nonequilibrium electronic transports through a double-QD-Majorana coupling system are studied with a purpose to extract the information to identify Majorana bound states (MBSs). It is found that MBSs can help form various transport processes, including the nonlocal crossed Andreev reflection, local resonant Andreev reflection, and cotunneling, depending on the relative position of two dot levels. These processes enrich the signature of average currents and noise correlations to probe the nature of MBSs. We further demonstrate the switching between the current peaks of crossed Andreev reflection and cotunneling, which is closely related to the nonlocal nature of Majorana fermions. We also propose effective physical pictures to understand these Majorana-assisted transports. - Highlights: • Majorana fermions are characterized in the signature of currents and noises. • Three types of tunneling mechanisms are realized separately. • The switching of crossed Andreev reflection and cotunneling is realized. • Concrete physical pictures are proposed to understand Majorana-assisted transports

  9. Innovative educational modules for the next generation of transportation professionals.

    Science.gov (United States)

    2012-07-01

    Basic science and mathematics competence, including awareness of engineering careers, gained in grades K12 forms the foundation of an educated, capable, and technical future transportation workforce. This project developed a series of educational ...

  10. Majorana fermion modulated nonequilibrium transport through double quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Ming-Xun [Laboratory of Quantum Engineering and Quantum Materials, ICMP and SPTE, South China Normal University, Guangzhou 510006 (China); Wang, Rui-Qiang, E-mail: rqwanggz@163.com [Laboratory of Quantum Engineering and Quantum Materials, ICMP and SPTE, South China Normal University, Guangzhou 510006 (China); Ai, Bao-Quan; Yang, Mou; Hu, Liang-Bin; Zhong, Qing-Hu [Laboratory of Quantum Engineering and Quantum Materials, ICMP and SPTE, South China Normal University, Guangzhou 510006 (China); Wang, Guang-Hui [Laboratory of Nanophotonic Functional Materials and Devices, South China Normal University, Guangzhou 510006 (China)

    2014-06-13

    Nonequilibrium electronic transports through a double-QD-Majorana coupling system are studied with a purpose to extract the information to identify Majorana bound states (MBSs). It is found that MBSs can help form various transport processes, including the nonlocal crossed Andreev reflection, local resonant Andreev reflection, and cotunneling, depending on the relative position of two dot levels. These processes enrich the signature of average currents and noise correlations to probe the nature of MBSs. We further demonstrate the switching between the current peaks of crossed Andreev reflection and cotunneling, which is closely related to the nonlocal nature of Majorana fermions. We also propose effective physical pictures to understand these Majorana-assisted transports. - Highlights: • Majorana fermions are characterized in the signature of currents and noises. • Three types of tunneling mechanisms are realized separately. • The switching of crossed Andreev reflection and cotunneling is realized. • Concrete physical pictures are proposed to understand Majorana-assisted transports.

  11. pH, Lactate, and Hypoxia: Reciprocity in Regulating High-Affinity Monocarboxylate Transporter Expression in Glioblastoma

    Directory of Open Access Journals (Sweden)

    James P. Caruso

    2017-02-01

    Full Text Available Highly malignant brain tumors harbor the aberrant propensity for aerobic glycolysis, the excessive conversion of glucose to lactic acid even in the presence of ample tissue oxygen. Lactic acid is rapidly effluxed to the tumor microenvironment via a group of plasma-membrane transporters denoted monocarboxylate transporters (MCTs to prevent “self-poisoning.” One isoform, MCT2, has the highest affinity for lactate and thus should have the ability to respond to microenvironment conditions such as hypoxia, lactate, and pH to help maintain high glycolytic flux in the tumor. Yet, MCT2 is considered to not respond to hypoxia, which is counterintuitive. Its response to tumor lactate has not been reported. In this report, we experimentally identify the transcription initiation site/s for MCT2 in astrocytes (normal and glioma (tumor. We then use a BACmid library to isolate a 4.2-kbp MCT2 promoter-exon I region and examine promoter response to glycolysis-mediated stimuli in glioma cells. Reporter analysis of nested-promoter constructs indicated response of MCT2 to hypoxia, pH, lactate, and glucose, the major physiological “players” that facilitate a tumor's growth and proliferation. Immunoblot analysis of native MCT2 expression under altered pH and hypoxia reflected the reporter data. The pH-mediated gene-regulation studies we describe are the first to record H+-based reporter studies for any mammalian system and demonstrate the exquisite response of the MCT2 gene to minute changes in tumor pH. Identical promoter usage also provides the first evidence of astrocytes harnessing the same gene regulatory regions to facilitate astrocyte-neuron lactate shuttling, a metabolic feature of normal brain.

  12. New insights into the interplay between the lysine transporter LysP and the pH sensor CadC in Escherichia coli.

    Science.gov (United States)

    Rauschmeier, Martina; Schüppel, Valentina; Tetsch, Larissa; Jung, Kirsten

    2014-01-09

    The coordination of signal transduction and substrate transport represents a sophisticated way to integrate information on metabolite fluxes into transcriptional regulation. This widely distributed process involves protein-protein interactions between two integral membrane proteins. Here we report new insights into the molecular mechanism of the regulatory interplay between the lysine-specific permease LysP and the membrane-integrated pH sensor CadC, which together induce lysine-dependent adaptation of E. coli under acidic stress. In vivo analyses revealed that, in the absence of either stimulus, the two proteins form a stable association, which is modulated by lysine and low pH. In addition to its transmembrane helix, the periplasmic domain of CadC also participated in the interaction. Site-directed mutagenesis pinpointed Arg265 and Arg268 in CadC as well as Asp275 and Asp278 in LysP as potential periplasmic interaction sites. Moreover, a systematic analysis of 100 LysP variants with single-site replacements indicated that the lysine signal is transduced from co-sensor to sensor via lysine-dependent conformational changes (upon substrate binding and/or transport) of LysP. Our results suggest a scenario in which CadC is inhibited by LysP via intramembrane and periplasmic contacts under non-inducing conditions. Upon induction, lysine-dependent conformational changes in LysP transduce the lysine signal via a direct conformational coupling to CadC without resolving the interaction completely. Moreover, concomitant pH-dependent protonation of periplasmic amino acids in both proteins dissolves their electrostatic connections resulting in further destabilization of the CadC/LysP interaction. © 2013.

  13. Cl- transport pathways regulated by Ca++, cAMP, and pH in human fibroblasts

    International Nuclear Information System (INIS)

    Lin, P.; Gruenstein, E.

    1987-01-01

    Under basal conditions Cl - efflux from human fibroblasts occurs with a rate constant of permeability of 0.08 min -1 . 50% of the basal efflux is due to Cl - /anion exchange and is DIDS inhibitable, 25% is due to Na + /K + /Cl - cotransport and is furosemide inhibitable, and 20% is due to an electrically conductive pathway. Increasing intracellular Ca ++ with A23187 stimulates Cl - efflux by 30%. This increase appears to occur entirely via an electrically conducting pathway, but unlike basal Cl - conductance, it is DIDS sensitive. Exposure of the cells to dibutyryl cAMP stimulates Cl - efflux by 15%. They do not yet know whether the cAMP stimulated pathway is electrically conductive, but the stimulation is additive with that caused by elevated Ca ++ suggesting that different pathways are activated. Elevation of intracellular pH by any of several standard methods increases Cl - efflux by as much as 700%. The pH effect appears to be mediated by a Cl - /anion exchange pathway since it is DIDS sensitive and electroneutral. Previous work from this laboratory describing a transient rapid efflux of Cl - followed by a slower efflux phase can now be explained as the result of a transient alkalinization of cells rather than as 2 subcellular Cl - compartments. This alkalinization occurs when cells are transferred from a 5% CO 2 atmosphere during 36 Cl - load to ambient CO 2 for efflux

  14. Impaired pH homeostasis in Arabidopsis lacking the vacuolar dicarboxylate transporter and analysis of carboxylic acid transport across the tonoplast.

    Science.gov (United States)

    Hurth, Marco Alois; Suh, Su Jeoung; Kretzschmar, Tobias; Geis, Tina; Bregante, Monica; Gambale, Franco; Martinoia, Enrico; Neuhaus, H Ekkehard

    2005-03-01

    Arabidopsis (Arabidopsis thaliana) mutants lacking the tonoplastic malate transporter AttDT (A. thaliana tonoplast dicarboxylate transporter) and wild-type plants showed no phenotypic differences when grown under standard conditions. To identify putative metabolic changes in AttDT knock-out plants, we provoked a metabolic scenario connected to an increased consumption of dicarboxylates. Acidification of leaf discs stimulated dicarboxylate consumption and led to extremely low levels of dicarboxylates in mutants. To investigate whether reduced dicarboxylate concentrations in mutant leaf cells and, hence, reduced capacity to produce OH(-) to overcome acidification might affect metabolism, we measured photosynthetic oxygen evolution under conditions where the cytosol is acidified. AttDT::tDNA protoplasts showed a much stronger inhibition of oxygen evolution at low pH values when compared to wild-type protoplasts. Apparently citrate, which is present in higher amounts in knock-out plants, is not able to replace dicarboxylates to overcome acidification. To raise more information on the cellular level, we performed localization studies of carboxylates. Although the total pool of carboxylates in mutant vacuoles was nearly unaltered, these organelles contained a lower proportion of malate and fumarate and a higher proportion of citrate when compared to wild-type vacuoles. These alterations concur with the observation that radioactively labeled malate and citrate are transported into Arabidopsis vacuoles by different carriers. In addition, wild-type vacuoles and corresponding organelles from AttDT::tDNA mutants exhibited similar malate channel activities. In conclusion, these results show that Arabidopsis vacuoles contain at least two transporters and a channel for dicarboxylates and citrate and that the activity of AttDT is critical for regulation of pH homeostasis.

  15. Impaired pH Homeostasis in Arabidopsis Lacking the Vacuolar Dicarboxylate Transporter and Analysis of Carboxylic Acid Transport across the Tonoplast1

    Science.gov (United States)

    Hurth, Marco Alois; Suh, Su Jeoung; Kretzschmar, Tobias; Geis, Tina; Bregante, Monica; Gambale, Franco; Martinoia, Enrico; Neuhaus, H. Ekkehard

    2005-01-01

    Arabidopsis (Arabidopsis thaliana) mutants lacking the tonoplastic malate transporter AttDT (A. thaliana tonoplast dicarboxylate transporter) and wild-type plants showed no phenotypic differences when grown under standard conditions. To identify putative metabolic changes in AttDT knock-out plants, we provoked a metabolic scenario connected to an increased consumption of dicarboxylates. Acidification of leaf discs stimulated dicarboxylate consumption and led to extremely low levels of dicarboxylates in mutants. To investigate whether reduced dicarboxylate concentrations in mutant leaf cells and, hence, reduced capacity to produce OH− to overcome acidification might affect metabolism, we measured photosynthetic oxygen evolution under conditions where the cytosol is acidified. AttDT::tDNA protoplasts showed a much stronger inhibition of oxygen evolution at low pH values when compared to wild-type protoplasts. Apparently citrate, which is present in higher amounts in knock-out plants, is not able to replace dicarboxylates to overcome acidification. To raise more information on the cellular level, we performed localization studies of carboxylates. Although the total pool of carboxylates in mutant vacuoles was nearly unaltered, these organelles contained a lower proportion of malate and fumarate and a higher proportion of citrate when compared to wild-type vacuoles. These alterations concur with the observation that radioactively labeled malate and citrate are transported into Arabidopsis vacuoles by different carriers. In addition, wild-type vacuoles and corresponding organelles from AttDT::tDNA mutants exhibited similar malate channel activities. In conclusion, these results show that Arabidopsis vacuoles contain at least two transporters and a channel for dicarboxylates and citrate and that the activity of AttDT is critical for regulation of pH homeostasis. PMID:15728336

  16. ZIFL1.1 transporter modulates polar auxin transport by stabilizing membrane abundance of multiple PINs in Arabidopsis root tip

    Science.gov (United States)

    Remy, Estelle; Baster, Pawel; Friml, Jiří; Duque, Paula

    2013-01-01

    Cell-to-cell directional flow of the phytohormone auxin is primarily established by polar localization of the PIN auxin transporters, a process tightly regulated at multiple levels by auxin itself. We recently reported that, in the context of strong auxin flows, activity of the vacuolar ZIFL1.1 transporter is required for fine-tuning of polar auxin transport rates in the Arabidopsis root. In particular, ZIFL1.1 function protects plasma-membrane stability of the PIN2 carrier in epidermal root tip cells under conditions normally triggering PIN2 degradation. Here, we show that ZIFL1.1 activity at the root tip also promotes PIN1 plasma-membrane abundance in central cylinder cells, thus supporting the notion that ZIFL1.1 acts as a general positive modulator of polar auxin transport in roots. PMID:23857365

  17. Ion transport membrane module and vessel system with directed internal gas flow

    Science.gov (United States)

    Holmes, Michael Jerome; Ohrn, Theodore R.; Chen, Christopher Ming-Poh

    2010-02-09

    An ion transport membrane system comprising (a) a pressure vessel having an interior, an inlet adapted to introduce gas into the interior of the vessel, an outlet adapted to withdraw gas from the interior of the vessel, and an axis; (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; and (c) one or more gas flow control partitions disposed in the interior of the pressure vessel and adapted to change a direction of gas flow within the vessel.

  18. Development and preliminary verification of 2-D transport module of radiation shielding code ARES

    International Nuclear Information System (INIS)

    Zhang Penghe; Chen Yixue; Zhang Bin; Zang Qiyong; Yuan Longjun; Chen Mengteng

    2013-01-01

    The 2-D transport module of radiation shielding code ARES is two-dimensional neutron and radiation shielding code. The theory model was based on the first-order steady state neutron transport equation, adopting the discrete ordinates method to disperse direction variables. Then a set of differential equations can be obtained and solved with the source iteration method. The 2-D transport module of ARES was capable of calculating k eff and fixed source problem with isotropic or anisotropic scattering in x-y geometry. The theoretical model was briefly introduced and series of benchmark problems were verified in this paper. Compared with the results given by the benchmark, the maximum relative deviation of k eff is 0.09% and the average relative deviation of flux density is about 0.60% in the BWR cells benchmark problem. As for the fixed source problem with isotropic and anisotropic scattering, the results of the 2-D transport module of ARES conform with DORT very well. These numerical results of benchmark problems preliminarily demonstrate that the development process of the 2-D transport module of ARES is right and it is able to provide high precision result. (authors)

  19. Specific Lipids Modulate the Transporter Associated with Antigen Processing (TAP)

    DEFF Research Database (Denmark)

    Scholz, C.; Parcej, D.; Ejsing, C. S.

    2011-01-01

    and structural analysis of this ATP-binding cassette complex, we established the overexpression of TAP in the methylotrophic yeast Pichia pastoris. Screening of optimal solubilization and purification conditions allowed the isolation of the heterodimeric transport complex, yielding 30 mg of TAP/liter of culture....... Detailed analysis of TAP function in the membrane, solubilized, purified, and reconstituted states revealed a direct influence of the native lipid environment on activity. TAP-associated phospholipids, essential for function, were profiled by liquid chromatography Fourier transform mass spectrometry...

  20. Spin transport through electric field modulated graphene periodic ferromagnetic barriers

    International Nuclear Information System (INIS)

    Sattari, F.; Faizabadi, E.

    2014-01-01

    Using the transfer matrix method, the spin transmission coefficient and the spin conductivity are studied theoretically through the monolayer and bilayer graphene periodic ferromagnetic barriers modulated by a homogeneous electric field. The spin conductivity of the systems has an oscillatory behavior with respect to the external electric field which depends on the spin state of electron. In addition, the oscillation amplitude of the spin conductivity and spin polarization increase by increasing the number of barriers, but for a monolayer system with number of barriers greater than thirty, also for a bilayer system with the number of barriers greater than four, the oscillation amplitude does not change significantly. Our probes show that for bilayer system unlike monolayer structure the highest value of spin polarization achieved can be 1 or (−1). So, for designing spintronic devices, bilayer graphene is more efficient

  1. A 'V' shaped superconducting levitation module for lift and guidance of a magnetic transportation system

    International Nuclear Information System (INIS)

    D'Ovidio, G.; Crisi, F.; Lanzara, G.

    2008-01-01

    A novel, YBCO based, magnetic transportation system (MagTranS) is presented and described. The feasibility of this system has been successfully tested and confirmed in a laboratory using a scaled demonstrator system. The MagTranS levitation system uses a stable, self-balancing 'V' shaped superconducting module for both lift and guidance of vehicles. The work concept of the MagTranS levitation module is described and differences with regards to the maglev current systems are highlighted. The results of levitation tests performed using a measurement set-up are presented and discussed. Lastly, levitation module performance studies are also carried out using numerical finite element analysis

  2. Coupling between particle and heat transport during power modulation experiments in Tore Supra

    International Nuclear Information System (INIS)

    Zou, X.L.; Giruzzi, G.; Artaud, J.F.; Bouquey, F.; Bremond, S.; Clary, J.; Darbos, C.; Eury, S.P.; Lennholm, M.; Magne, R.; Segui, J.L.

    2004-01-01

    Power modulations are a powerful tool often used to investigate heat transport processes in tokamaks. In some situations, this could also be an interesting method for the investigation of the particle transport due to the anomalous pinch. Low frequency (∼ 1 Hz) power modulation experiments, using both electron cyclotron resonance heating (ECRH) and ion cyclotron resonance heating (ICRH), have been performed in the Tore Supra tokamak. Strong coupling has been observed between the temperature and density modulations during the low frequency ECRH and ICRH modulation experiments. It has been shown that mechanisms as outgassing, Ware pinch effect, curvature driven pinch are not likely to be responsible for this density modulation. Because of its dependence on temperature or temperature gradient, the thermodiffusion is a serious candidate to be the driving source for this density modulation. This analysis shows that low frequency power modulation experiments have a great potential for the investigation of the anomalous particle pinch in tokamaks. Future plans will include the use of more precise density profile measurements using X-mode reflectometry

  3. Coupling between particle and heat transport during power modulation experiments in Tore Supra

    Energy Technology Data Exchange (ETDEWEB)

    Zou, X.L.; Giruzzi, G.; Artaud, J.F.; Bouquey, F.; Bremond, S.; Clary, J.; Darbos, C.; Eury, S.P.; Lennholm, M.; Magne, R.; Segui, J.L

    2004-07-01

    Power modulations are a powerful tool often used to investigate heat transport processes in tokamaks. In some situations, this could also be an interesting method for the investigation of the particle transport due to the anomalous pinch. Low frequency ({approx} 1 Hz) power modulation experiments, using both electron cyclotron resonance heating (ECRH) and ion cyclotron resonance heating (ICRH), have been performed in the Tore Supra tokamak. Strong coupling has been observed between the temperature and density modulations during the low frequency ECRH and ICRH modulation experiments. It has been shown that mechanisms as outgassing, Ware pinch effect, curvature driven pinch are not likely to be responsible for this density modulation. Because of its dependence on temperature or temperature gradient, the thermodiffusion is a serious candidate to be the driving source for this density modulation. This analysis shows that low frequency power modulation experiments have a great potential for the investigation of the anomalous particle pinch in tokamaks. Future plans will include the use of more precise density profile measurements using X-mode reflectometry.

  4. Modeling particle-facilitated solute transport using the C-Ride module of HYDRUS

    Science.gov (United States)

    Simunek, Jiri; Bradford, Scott A.

    2017-04-01

    Strongly sorbing chemicals (e.g., heavy metals, radionuclides, pharmaceuticals, and/or explosives) in soils are associated predominantly with the solid phase, which is commonly assumed to be stationary. However, recent field- and laboratory-scale observations have shown that, in the presence of mobile colloidal particles (e.g., microbes, humic substances, clays and metal oxides), the colloids could act as pollutant carriers and thus provide a rapid transport pathway for strongly sorbing contaminants. Such transport can be further accelerated since these colloidal particles may travel through interconnected larger pores where the water velocity is relatively high. Additionally, colloidal particles have a considerable adsorption capacity for other species present in water because of their large specific surface areas and their high concentrations in soil-water and groundwater. As a result, the transport of contaminants can be significantly, sometimes dramatically, enhanced when they are adsorbed to mobile colloids. To address this problem, we have developed the C-Ride module for HYDRUS-1D. This one-dimensional numerical module is based on the HYDRUS-1D software package and incorporates mechanisms associated with colloid and colloid-facilitated solute transport in variably saturated porous media. This numerical model accounts for both colloid and solute movement due to convection, diffusion, and dispersion in variably-saturated soils, as well as for solute movement facilitated by colloid transport. The colloids transport module additionally considers processes of attachment/detachment to/from the solid phase, straining, and/or size exclusion. Various blocking and depth dependent functions can be used to modify the attachment and straining coefficients. The module additionally considers the effects of changes in the water content on colloid/bacteria transport and attachment/detachment to/from solid-water and air-water interfaces. For example, when the air

  5. Experimental tests of transport models using modulated ECH

    International Nuclear Information System (INIS)

    DeBoo, J.C.; Kinsey, J.E.; Bravenec, R.

    1998-12-01

    Both the dynamic and equilibrium thermal responses of an L-mode plasma to repetitive ECH heat pulses were measured and compared to predictions from several thermal transport models. While no model consistently agreed with all observations, the GLF23 model was most consistent with the perturbated electron and ion temperature responses for one of the cases studied which may indicate a key role played by electron modes in the core of these discharges. Generally, the IIF and MM models performed well for the perturbed electron response while the GLF23 and IFS/PPPL models agreed with the perturbed ion response for all three cases studied. No single model agreed well with the equilibrium temperature profiles measured

  6. PhreeqcRM: A reaction module for transport simulators based on the geochemical model PHREEQC

    Science.gov (United States)

    Parkhurst, David L.; Wissmeier, Laurin

    2015-01-01

    PhreeqcRM is a geochemical reaction module designed specifically to perform equilibrium and kinetic reaction calculations for reactive transport simulators that use an operator-splitting approach. The basic function of the reaction module is to take component concentrations from the model cells of the transport simulator, run geochemical reactions, and return updated component concentrations to the transport simulator. If multicomponent diffusion is modeled (e.g., Nernst–Planck equation), then aqueous species concentrations can be used instead of component concentrations. The reaction capabilities are a complete implementation of the reaction capabilities of PHREEQC. In each cell, the reaction module maintains the composition of all of the reactants, which may include minerals, exchangers, surface complexers, gas phases, solid solutions, and user-defined kinetic reactants.PhreeqcRM assigns initial and boundary conditions for model cells based on standard PHREEQC input definitions (files or strings) of chemical compositions of solutions and reactants. Additional PhreeqcRM capabilities include methods to eliminate reaction calculations for inactive parts of a model domain, transfer concentrations and other model properties, and retrieve selected results. The module demonstrates good scalability for parallel processing by using multiprocessing with MPI (message passing interface) on distributed memory systems, and limited scalability using multithreading with OpenMP on shared memory systems. PhreeqcRM is written in C++, but interfaces allow methods to be called from C or Fortran. By using the PhreeqcRM reaction module, an existing multicomponent transport simulator can be extended to simulate a wide range of geochemical reactions. Results of the implementation of PhreeqcRM as the reaction engine for transport simulators PHAST and FEFLOW are shown by using an analytical solution and the reactive transport benchmark of MoMaS.

  7. Optimization of Intracellular Transportation of Gene Therapeutic DNA in Small Cell Lung Cancer (Ph.d.)

    DEFF Research Database (Denmark)

    Cramer, Frederik

    2013-01-01

    Small cell lung cancer (SCLC) is a highly malignant disease characterized as being very aggressive and metastasizing at a rapid pace. The malevolent pace of SCLC cell migration results in almost three out of four SCLC patients having disseminated SCLC at the time of diagnosis. Unfortunately...... has to be able to repeated systemic delivery of gene therapy to cancer cells in a both safe and efficient way. Non-viral delivery vectors fulfill many of these requirements except the latter. It is currently very difficult to systemically transport sufficient amounts of therapeutic DNA, by a non......-viral delivery system, to the nuclei of the SCLC cells. As a result, the gene therapy expression obtained is too low to have any clinical relevance. We have at the Department of Radiation Biology developed a transcriptionally targeting suicide gene therapy system which is built on a double stranded DNA plasmid...

  8. Computer module for scheduling of transportation of composite beam bridge structures

    Directory of Open Access Journals (Sweden)

    Bożejko Wojciech

    2016-01-01

    Full Text Available The paper presents the theoretical basis, an algorithm and a computer module system supporting scheduling of transportation and assembly of structures of the composite beam bridge implemented in a Just In Time system (JIT. Tabu search method has been used in the optimization procedure.

  9. ANAUSN - a one-dimensional multigroup SN transport theory module for the AUS reactor neutronics system

    International Nuclear Information System (INIS)

    Clancy, B.E.

    1982-05-01

    ANAUSN is a general purpose, one-dimensional discrete ordinate transport theory program which has access to AUS datapools. Fixed source, reactivity and a variety of criticality search calculations can be performed. The program can be operated as a module in the AUS scheme or as a stand-alone program

  10. Effect of Microenvironmental pH Modulation on the Dissolution Rate and Oral Absorption of the Salt of a Weak Acid - Case Study of GDC-0810.

    Science.gov (United States)

    Hou, Hao Helen; Jia, Wei; Liu, Lichuan; Cheeti, Sravanthi; Li, Jane; Nauka, Ewa; Nagapudi, Karthik

    2018-01-29

    The purpose of this work is to investigate the effect of microenvironmental pH modulation on the in vitro dissolution rate and oral absorption of GDC-0810, an oral anti-cancer drug, in human. The pH-solubility profile of GDC-0810 free acid and pH max of its N-Methyl-D-glucamine (NMG) salt were determined. Precipitation studies were conducted for GDC-0810 NMG salt at different pH values. GDC-0810 200-mg dose NMG salt tablet formulations containing different levels of sodium bicarbonate as the pH modifier were tested for dissolution under the dual pH-dilution scheme. Three tablet formulations were evaluated in human as a part of a relative bioavailability study. A 200-mg dose of GDC-0810 was administered QD with low fat food. Intrinsic solubility of GDC-0810 free acid was found to be extremely low. The pH max of the NMG salt suggested a strong tendency for form conversion to the free acid under GI conditions. In vitro dissolution profiles showed that the dissolution rate and extent of GDC-0810 increased with increasing the level of sodium bicarbonate in the formulation. The human PK data showed a similar trend for the geometric mean of C max and AUC 0-t for formulations containing 5%, 10%, and 15% sodium bicarbonate, but the difference is not statistically significant. Incorporation of a basic pH modifier, sodium bicarbonate, in GDC-0810 NMG salt tablet formulations enhanced in vitro dissolution rate of GDC-0810 via microenvironmental pH modulation. The human PK data showed no statistically significant difference in drug exposure from tablets containing 5%, 10%, and 15% sodium bicarbonate.

  11. Modulation of Intestinal Paracellular Transport by Bacterial Pathogens.

    Science.gov (United States)

    Roxas, Jennifer Lising; Viswanathan, V K

    2018-03-25

    The passive and regulated movement of ions, solutes, and water via spaces between cells of the epithelial monolayer plays a critical role in the normal intestinal functioning. This paracellular pathway displays a high level of structural and functional specialization, with the membrane-spanning complexes of the tight junctions, adherens junctions, and desmosomes ensuring its integrity. Tight junction proteins, like occludin, tricellulin, and the claudin family isoforms, play prominent roles as barriers to unrestricted paracellular transport. The past decade has witnessed major advances in our understanding of the architecture and function of epithelial tight junctions. While it has been long appreciated that microbes, notably bacterial and viral pathogens, target and disrupt junctional complexes and alter paracellular permeability, the precise mechanisms remain to be defined. Notably, renewed efforts will be required to interpret the available data on pathogen-mediated barrier disruption in the context of the most recent findings on tight junction structure and function. While much of the focus has been on pathogen-induced dysregulation of junctional complexes, commensal microbiota and their products may influence paracellular permeability and contribute to the normal physiology of the gut. Finally, microbes and their products have become important tools in exploring host systems, including the junctional properties of epithelial cells. © 2018 American Physiological Society. Compr Physiol 8:823-842, 2018. Copyright © 2018 American Physiological Society. All rights reserved.

  12. Dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs with poor water solubility.

    Science.gov (United States)

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Lee, Kyoung-Ho; Kim, Dong-Jin; Lee, Beom-Jin

    2010-05-01

    Although the solid dispersion method has been known to increase the dissolution rate of poorly water-soluble drugs by dispersing them in hydrophilic carriers, one obstacle of the solid dispersion method is its limited solubilization capacity, especially for pH-dependent soluble drugs. pH-modified solid dispersion, in which pH modifiers are incorporated, may be a useful method for increasing the dissolution rate of weakly acidic or basic drugs. Sufficient research, including the most recent reports, was undertaken in this review. How could the inclusion of the pH the pH modifiers in the solid dispersion system change drug structural behaviors, molecular interactions, microenvironmental pH, and/or release rate of pH modifiers, relating with the enhanced dissolution of weakly acidic or weakly basic drugs with poor water solubility? These questions have been investigated to determine the dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs. It is believed that step-by-step mechanistic approaches could provide the ultimate solution for solubilizing several poorly water-soluble drugs with pH-dependent solubility from a solid dispersion system, as well as provide ideas for developing future dosage systems.

  13. Modulation of phosducin-like protein 3 (PhLP3 levels promotes cytoskeletal remodelling in a MAPK and RhoA-dependent manner.

    Directory of Open Access Journals (Sweden)

    Nandini V L Hayes

    Full Text Available Phosducin-like protein 3 (PhLP3 forms a ternary complex with the ATP-dependent molecular chaperone CCT and its folding client tubulin. In vitro studies suggest PhLP3 plays an inhibitory role in β-tubulin folding while conversely in vivo genetic studies suggest PhLP3 is required for the correct folding of β-tubulin. We have a particular interest in the cytoskeleton, its chaperones and their role in determining cellular phenotypes associated with high level recombinant protein expression from mammalian cell expression systems.As studies into PhLP3 function have been largely carried out in non mammalian systems, we examined the effect of human PhLP3 over-expression and siRNA silencing using a single murine siRNA on both tubulin and actin systems in mammalian Chinese hamster ovary (CHO cell lines. We show that over-expression of PhLP3 promotes an imbalance of α and β tubulin subunits, microtubule disassembly and cell death. In contrast, β-actin levels are not obviously perturbed. On-the-other-hand, RNA silencing of PhLP3 increases RhoA-dependent actin filament formation and focal adhesion formation and promotes a dramatic elongated fibroblast-like change in morphology. This was accompanied by an increase in phosphorylated MAPK which has been associated with promoting focal adhesion assembly and maturation. Transient overexpression of PhLP3 in knockdown experiments rescues cells from the morphological change observed during PhLP3 silencing but mitosis is perturbed, probably reflecting a tipping back of the balance of PhLP3 levels towards the overexpression state.Our results support the hypothesis that PhLP3 is important for the maintenance of β-tubulin levels in mammalian cells but also that its modulation can promote actin-based cytoskeletal remodelling by a mechanism linked with MAPK phosphorylation and RhoA-dependent changes. PhLP3 levels in mammalian cells are thus finely poised and represents a novel target for engineering industrially

  14. Modulation of leak K(+) channel in hypoglossal motoneurons of rats by serotonin and/or variation of pH value.

    Science.gov (United States)

    Xu, Xue-Feng; Tsai, Hao-Jan; Li, Lin; Chen, Yi-Fan; Zhang, Cheng; Wang, Guang-Fa

    2009-08-25

    The cloned TWIK-related acid-sensitive K(+) channel (TASK-1) is sensitive to the pH changes within physiological pH range (pK~7.4). Recently, the native TASK-1-like channel was suggested to be the main contributor to the background (or leak) K(+) conductance in the motoneurons of the brain stem. Serotonin (5-HT) and variation of pH value in perfused solution could modulate these currents. Here we aimed to examine the properties and modulation of the currents by serotonin or variation of pH value in hypoglossal motoneurons of rats. Transverse slices were prepared from the brainstem of neonatal Sprague-Dawley rats (postnatal days 7-8). Hypoglossal motoneurons were used for the study. The leak K(+) current (TASK-1-like current) and hyperpolarization-activated cationic current (I(h)) were recorded with the whole-cell patch-clamp technique. The results showed that these currents were inhibited by acidified artificial cerebrospinal fluid (ACSF, pH 6.0) and activated by alkalized ACSF (pH 8.5). 5-HT (10 mumol/L) significantly inhibited both leak K(+) current and I(h) with depolarization of membrane potential and the occurrence of oscillation and/or spikes. Bath application of Ketanserine, an antagonist of 5-HT₂ receptor, reversed or reduced the inhibitory effect of acidified solution on leak K(+) current and I(h). The results suggest that 5-HT₂ receptors mediate the effects of acidified media on leak K(+) current and I(h) in hypoglossal motoneurons.

  15. Development of whole core thermal-hydraulic analysis program ACT. 3. Coupling core module with primary heat transport system module

    International Nuclear Information System (INIS)

    Ohtaka, Masahiko; Ohshima, Hiroyuki

    1998-10-01

    A whole core thermal-hydraulic analysis program ACT is being developed for the purpose of evaluating detailed in-core thermal hydraulic phenomena of fast reactors including inter-wrapper flow under various reactor operation conditions. In this work, the core module as a main part of the ACT developed last year, which simulates thermal-hydraulics in the subassemblies and the inter-subassembly gaps, was coupled with an one dimensional plant system thermal-hydraulic analysis code LEDHER to simulate transients in the primary heat transport system and to give appropriate boundary conditions to the core model. The effective algorithm to couple these two calculation modules was developed, which required minimum modification of them. In order to couple these two calculation modules on the computing system, parallel computing technique using PVM (Parallel Virtual Machine) programming environment was applied. The code system was applied to analyze an out-of-pile sodium experiment simulating core with 7 subassemblies under transient condition for code verification. It was confirmed that the analytical results show a similar tendency of experimental results. (author)

  16. SU-E-P-04: Transport Theory Learning Module in the Maple Environment

    Energy Technology Data Exchange (ETDEWEB)

    Both, J [University of Miami, Miller School of Medicine, Department of Radiation Oncology (United States)

    2014-06-01

    Purpose: The medical physics graduate program at the University of Miami is developing a computerized instructional module which provides an interactive mechanism for students to learn transport theory. While not essential in the medical physics curriculum, transport theory should be taught because the conceptual level of transport theory is fundamental, a substantial literature exists and ought to be accessible, and students should understand commercial software which solves the Boltzmann equation.But conventional teaching and learning of transport theory is challenging. Students may be under prepared to appreciate its methods, results, and relevance, and it is not substantially addressed in textbooks for the medical physicists. Other resources an instructor might reasonably use, while excellent, may be too briskly paced for beginning students. The purpose of this work is to render teaching of transport theory more tractable by making learning highly interactive. Methods: The module is being developed in the Maple mathematics environment by instructors and graduate students. It will refresh the students' knowledge of vector calculus and differential equations, and will develop users' intuition for phase space concepts. Scattering concepts will be developed with animated simulations using tunable parameters characterizing interactions, so that students may develop a “feel” for cross section. Transport equations for one and multiple types of radiation will be illustrated with phase space animations. Numerical methods of solution will be illustrated. Results: Attempts to teach rudiments of transport theory in radiation physics and dosimetry courses using conventional classroom techniques at the University of Miami have had small success, because classroom time is limited and the material has been hard for our students to appreciate intuitively. Conclusion: A joint effort of instructor and students to teach and learn transport theory by building an

  17. SU-E-P-04: Transport Theory Learning Module in the Maple Environment

    International Nuclear Information System (INIS)

    Both, J

    2014-01-01

    Purpose: The medical physics graduate program at the University of Miami is developing a computerized instructional module which provides an interactive mechanism for students to learn transport theory. While not essential in the medical physics curriculum, transport theory should be taught because the conceptual level of transport theory is fundamental, a substantial literature exists and ought to be accessible, and students should understand commercial software which solves the Boltzmann equation.But conventional teaching and learning of transport theory is challenging. Students may be under prepared to appreciate its methods, results, and relevance, and it is not substantially addressed in textbooks for the medical physicists. Other resources an instructor might reasonably use, while excellent, may be too briskly paced for beginning students. The purpose of this work is to render teaching of transport theory more tractable by making learning highly interactive. Methods: The module is being developed in the Maple mathematics environment by instructors and graduate students. It will refresh the students' knowledge of vector calculus and differential equations, and will develop users' intuition for phase space concepts. Scattering concepts will be developed with animated simulations using tunable parameters characterizing interactions, so that students may develop a “feel” for cross section. Transport equations for one and multiple types of radiation will be illustrated with phase space animations. Numerical methods of solution will be illustrated. Results: Attempts to teach rudiments of transport theory in radiation physics and dosimetry courses using conventional classroom techniques at the University of Miami have had small success, because classroom time is limited and the material has been hard for our students to appreciate intuitively. Conclusion: A joint effort of instructor and students to teach and learn transport theory by building an interactive

  18. A novel flow cytometric HTS assay reveals functional modulators of ATP binding cassette transporter ABCB6.

    Science.gov (United States)

    Polireddy, Kishore; Khan, Mohiuddin Md Taimur; Chavan, Hemantkumar; Young, Susan; Ma, Xiaochao; Waller, Anna; Garcia, Matthew; Perez, Dominique; Chavez, Stephanie; Strouse, Jacob J; Haynes, Mark K; Bologa, Cristian G; Oprea, Tudor I; Tegos, George P; Sklar, Larry A; Krishnamurthy, Partha

    2012-01-01

    ABCB6 is a member of the adenosine triphosphate (ATP)-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS), can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6's ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity.

  19. A novel flow cytometric HTS assay reveals functional modulators of ATP binding cassette transporter ABCB6.

    Directory of Open Access Journals (Sweden)

    Kishore Polireddy

    Full Text Available ABCB6 is a member of the adenosine triphosphate (ATP-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS, can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6's ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity.

  20. Magnetically Modulated Heat Transport in a Global Simulation of Solar Magneto-convection

    Energy Technology Data Exchange (ETDEWEB)

    Cossette, Jean-Francois [Laboratory for Atmospheric and Space Physics, Campus Box 600, University of Colorado, Boulder, CO 80303 (United States); Charbonneau, Paul [Département de Physique, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, QC H3C 3J7 (Canada); Smolarkiewicz, Piotr K. [European Centre for Medium-Range Weather Forecasts, Reading, RG2 9AX (United Kingdom); Rast, Mark P., E-mail: Jean-Francois.Cossette@lasp.colorado.edu, E-mail: paulchar@astro.umontreal.ca, E-mail: smolar@ecmwf.int, E-mail: Mark.Rast@lasp.colorado.edu [Department of Astrophysical and Planetary Sciences, Laboratory for Atmospheric and Space Physics, Campus Box 391, University of Colorado, Boulder, CO 80303 (United States)

    2017-05-20

    We present results from a global MHD simulation of solar convection in which the heat transported by convective flows varies in-phase with the total magnetic energy. The purely random initial magnetic field specified in this experiment develops into a well-organized large-scale antisymmetric component undergoing hemispherically synchronized polarity reversals on a 40 year period. A key feature of the simulation is the use of a Newtonian cooling term in the entropy equation to maintain a convectively unstable stratification and drive convection, as opposed to the specification of heating and cooling terms at the bottom and top boundaries. When taken together, the solar-like magnetic cycle and the convective heat flux signature suggest that a cyclic modulation of the large-scale heat-carrying convective flows could be operating inside the real Sun. We carry out an analysis of the entropy and momentum equations to uncover the physical mechanism responsible for the enhanced heat transport. The analysis suggests that the modulation is caused by a magnetic tension imbalance inside upflows and downflows, which perturbs their respective contributions to heat transport in such a way as to enhance the total convective heat flux at cycle maximum. Potential consequences of the heat transport modulation for solar irradiance variability are briefly discussed.

  1. Polymeric nanocarriers for transport modulation across the pulmonary epithelium: dendrimers, polymeric nanoparticles, and their nanoblends.

    Science.gov (United States)

    Bharatwaj, Balaji; Dimovski, Radovan; Conti, Denise S; da Rocha, Sandro R P

    2014-05-01

    The purpose of this study was to (a) Determine the cellular transport and uptake of amine-terminated generation 3 (G3) poly(amido amine) (PAMAM) dendrimers across an in vitro model of the pulmonary epithelium, and the ability to modulate their transport by forming nanoblends of the dendrimers with biodegradable solid polymeric nanoparticles (NPs) and (b) to formulate dendrimer nanocarriers in portable oral inhalation devices and evaluate their aerosol characteristics. To that end, fluorescein isothiocyanate (FITC)-labeled G3 PAMAM dendrimer nanocarriers (DNCs) were synthesized, and also encapsulated within poly lactide-co-glycolide nanoparticles (NPs). Transport and uptake of both DNCs encapsulated within NPs (nanoblends) and unencapsulated DNCs were tracked across polarized monolayers of airway epithelial cells, Calu-3. DNCs were also formulated as core-shell microparticles in pressurized metered-dose inhalers (pMDIs) and their aerodynamic properties evaluated by Andersen cascade impaction. The apparent permeability of DNCs across the airway epithelial model was similar to that of a paracellular marker of comparable molar mass--order of 10(-7) cm s(-1). The transport and cellular internalization of the DNCs can be modulated by formulating them as nanoblends. The transport of the DNCs across the lung epithelium was completely suppressed within the time of the experiment (5 h) when formulated as blends. The encapsulation also prevents saturation of the cellular internalization profile. Nanoblending may be a potential strategy to modulate the rate of transport and cellular uptake of DNCs, and thus be used as a design strategy to achieve enhanced local or systemic drug delivery.

  2. Temporal viscosity modulations driven by a pH sensitive polymer coupled to a pH-changing chemical reaction.

    Science.gov (United States)

    Escala, D M; Muñuzuri, A P; De Wit, A; Carballido-Landeira, J

    2017-05-17

    The Formaldehyde-Sulfite (FS) and the Formaldehyde-Sulfite-Gluconolactone (FSG) systems are examples of complex chemical reactions accompanied by well-controlled variations in pH. While the FS system exhibits a clock behavior, in the FSG reaction, this mechanism is coupled with the hydrolysis of the gluconolactone which gives the possibility to show large temporal oscillations of pH in an open reactor. In this work, we show how these reactive systems, due to their organic nature, can be coupled with pH sensitive polymers, particularly with polyacrylic acid (PAA) to trigger temporal changes of viscosity. We characterize this coupled reactive system showing the effects of changes in the initial concentrations of the polymer and in the chemical reagents on the induction time, the magnitude of the pH variations and the temporal modifications of the viscosity.

  3. Diffusive-to-ballistic transition of the modulated heat transport in a rarefied air chamber

    Science.gov (United States)

    Gomez-Heredia, C. L.; Macias, J.; Ordonez-Miranda, J.; Ares, O.; Alvarado-Gil, J. J.

    2017-01-01

    Modulated heat transfer in air subject to pressures from 760 Torr to 10-4 Torr is experimentally studied by means of a thermal-wave resonant cavity placed in a vacuum chamber. This is done through the analysis of the amplitude and phase delay of the photothermal signal as a function of the cavity length and pressure through of the Knudsen's number. The viscous, transitional, and free molecular regimes of heat transport are observed for pressures P>1.5 Torr, 25 mTorrheat transport.

  4. Fluvial modulation of hydrodynamics and salt transport in a highly stratified estuary

    Directory of Open Access Journals (Sweden)

    Carla de Abreu D'Aquino

    2010-06-01

    Full Text Available An oceanographic campaign was conducted in the Araranguá river estuary during the period from May 11th to 13th of 2006 in order to produce a first hydrographic characterization of this system. The campaign was carried out during the spring tide period, and coincidentally after an intense rain event in the region which produced a peak in river discharge. Water level, currents and salinity time series were recorded hourly during a 50-hour period, at a site nearly 7 km upstream from the estuarine mouth. Two longitudinal distributions of salinity along the estuary were also recorded. The hydrographic data time-series were used to compute the advective salt flux in order to investigate the changes in the transport terms as a function of the change in discharge. The results showed that the estuarine structure was strongly modulated by the river discharge. The drop in water level of about 0.5 m during the first 24 hours was directly related to the ebb phase of the river flood. The water column was highly stratified throughout the period, therefore the stratification increased during the last 24 hours. The currents were stronger, ebbing and uni-directional at the beginning and became weaker and bidirectional as the water level went down, assuming a tidal pattern. The total salt transport in the first 25 hours was of -13.6 kg.m-1.s-1 (seawards, decreasing to 3 Kg.m-1.s-1 during the last 25 hours (landwards. It was also noticeable that the pH in the estuary, recorded together with the salinity, was around 5, showing that the water quality in the estuary is affected by the coal mining activity in the hydrographic basin.Uma campanha oceanográfica foi realizada no estuário do rio Araranguá durante o período de 11 e 13 de maio de 2006, objetivando fazer uma primeira caracterização hidrográfica do sistema. A campanha foi realizada em condição de maré de sizígia, e coincidentemente após um evento de chuvas intensas na região que produziu um pico

  5. A Novel Mechanism of pH Buffering in C. elegans Glia: Bicarbonate Transport via the Voltage-Gated ClC Cl− Channel CLH-1

    Science.gov (United States)

    Grant, Jeff; Matthewman, Cristina

    2015-01-01

    An important function of glia is the maintenance of the ionic composition and pH of the synaptic microenvironment. In terms of pH regulation, HCO3− buffering has been shown to be important in both glia and neurons. Here, we used in vivo fluorescent pH imaging and RNA sequencing of the amphid sheath glia of Caenorhabditis elegans to reveal a novel mechanism of cellular HCO3− uptake. While the classical mechanism of HCO3− uptake involves Na+/HCO3− cotransporters, here we demonstrate that the C. elegans ClC Cl− channel CLH-1 is highly permeable to HCO3− and mediates HCO3− uptake into amphid sheath glia. CLH-1 has homology and electrophysiological properties similar to the mammalian ClC-2 Cl− channel. Our data suggest that, in addition to maintaining synaptic Cl− concentration, these channels may also be involved in maintenance of synaptic pH via HCO3− flux. These findings provide an exciting new facet of study regarding how pH is regulated in the brain. SIGNIFICANCE STATEMENT Maintenance of pH is essential for the physiological function of the nervous system. HCO3− is crucial for pH regulation and is transported into the cell via ion transporters, including ion channels, the molecular identity of which remains unclear. In this manuscript, we describe our discovery that the C. elegans amphid sheath glia regulate intracellular pH via HCO3− flux through the voltage-gated ClC channel CLH-1. This represents a novel function for ClC channels, which has implications for their possible role in mammalian glial pH regulation. This discovery may also provide a novel therapeutic target for pathologic conditions, such as ischemic stroke where acidosis leads to widespread death of glia and subsequently neurons. PMID:26674864

  6. A Novel Mechanism of pH Buffering in C. elegans Glia: Bicarbonate Transport via the Voltage-Gated ClC Cl- Channel CLH-1.

    Science.gov (United States)

    Grant, Jeff; Matthewman, Cristina; Bianchi, Laura

    2015-12-16

    An important function of glia is the maintenance of the ionic composition and pH of the synaptic microenvironment. In terms of pH regulation, HCO3 (-) buffering has been shown to be important in both glia and neurons. Here, we used in vivo fluorescent pH imaging and RNA sequencing of the amphid sheath glia of Caenorhabditis elegans to reveal a novel mechanism of cellular HCO3 (-) uptake. While the classical mechanism of HCO3 (-) uptake involves Na(+)/HCO3 (-) cotransporters, here we demonstrate that the C. elegans ClC Cl(-) channel CLH-1 is highly permeable to HCO3 (-) and mediates HCO3 (-) uptake into amphid sheath glia. CLH-1 has homology and electrophysiological properties similar to the mammalian ClC-2 Cl(-) channel. Our data suggest that, in addition to maintaining synaptic Cl(-) concentration, these channels may also be involved in maintenance of synaptic pH via HCO3 (-) flux. These findings provide an exciting new facet of study regarding how pH is regulated in the brain. Maintenance of pH is essential for the physiological function of the nervous system. HCO3 (-) is crucial for pH regulation and is transported into the cell via ion transporters, including ion channels, the molecular identity of which remains unclear. In this manuscript, we describe our discovery that the C. elegans amphid sheath glia regulate intracellular pH via HCO3 (-) flux through the voltage-gated ClC channel CLH-1. This represents a novel function for ClC channels, which has implications for their possible role in mammalian glial pH regulation. This discovery may also provide a novel therapeutic target for pathologic conditions, such as ischemic stroke where acidosis leads to widespread death of glia and subsequently neurons. Copyright © 2015 the authors 0270-6474/15/3516377-21$15.00/0.

  7. Magnetic Modulation of the Transport of Organophilic Solutes through Supported Magnetic Ionic Liquid Membranes.

    Czech Academy of Sciences Publication Activity Database

    Daniel, C.L.; Rubio, A.M.; Sebastião, P.J.; Afonso, C.A.M.; Storch, Jan; Izák, Pavel; Portugal, C.A.M.; Crespo, J.G.

    2016-01-01

    Roč. 505, MAY 1 (2016), s. 36-43 ISSN 0376-7388 R&D Projects: GA ČR(CZ) GAP106/12/0569 Grant - others:ERANET(PT) ERA-CHEM/0001/2008; EUI(ES) 2008- 03857; FCT-MCTES(PT) SFRH/BD/81552/2011 Institutional support: RVO:67985858 Keywords : magnetic ionic liquids (MILs) * solute transport modulation * magnetic field Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 6.035, year: 2016

  8. Periodically modulated single-photon transport in one-dimensional waveguide

    Science.gov (United States)

    Li, Xingmin; Wei, L. F.

    2018-03-01

    Single-photon transport along a one-dimension waveguide interacting with a quantum system (e.g., two-level atom) is a very useful and meaningful simplified model of the waveguide-based optical quantum devices. Thus, how to modulate the transport of the photons in the waveguide structures by adjusting certain external parameters should be particularly important. In this paper, we discuss how such a modulation could be implemented by periodically driving the energy splitting of the interacting atom and the atom-photon coupling strength. By generalizing the well developed time-independent full quantum mechanical theory in real space to the time-dependent one, we show that various sideband-transmission phenomena could be observed. This means that, with these modulations the photon has certain probabilities to transmit through the scattering atom in the other energy sidebands. Inversely, by controlling the sideband transmission the periodic modulations of the single photon waveguide devices could be designed for the future optical quantum information processing applications.

  9. Transport and Retention of TiO2 Rutile Nanoparticles in Saturated Porous Media: Influence of Solution pH, Ionic Strength, and the Presence of Humic Acid

    Science.gov (United States)

    The influence of solution pH, ionic strength, and varying concentrations of the Suwannee River Humic Acid (SRHA) on the transport of titanium dioxide (TiO2, rutile) nanoparticle aggregates (nTiO2) in saturated porous media was investigated through systematically examining the tra...

  10. pH modulation and salivary sugar clearance of different chocolates in children: A randomized clinical trial

    Directory of Open Access Journals (Sweden)

    SVSG Nirmala

    2016-01-01

    Full Text Available Background: Sugars that occur naturally in foods and those added in processed foods may act as the source for fermentable carbohydrates and may initiate caries process. Among all the foods consumed by children, chocolates form an important constituent. A wide variety of chocolates are available in the Indian market and very few studies have compared their acidogenicity and salivary sugar clearance. Objectives: To compare the acidogenicity and salivary sugar clearance of 6 different commercially available chocolates in the Indian market. Materials and Methods: Thirty subjects aged 10-15 years were selected randomly from one of the available public schools in Nellore city. Six commercially available chocolates in the Indian market were divided into three groups, unfilled (dark and milk chocolate, filled (wafer and fruit and nuts chocolate, and candy (hard milk and mango-flavored candy groups. Plaque pH values and salivary sugar clearance rates are assessed at baseline, 5, 10, 15, 20, and 30 min after consumption. All the data obtained were statistically evaluated using independent sample t-test and one-way ANOVA for multiple group comparisons. Results: Mango-flavored candy had maximum fall in plaque pH and least fall in plaque pH was recorded with milk chocolate. Fruit and nuts chocolate had a maximum clearance of salivary sugar and least fall in the salivary sugar clearance was recorded with dark chocolate. When the plaque pH and salivary sugar clearance of all the chocolates were assessed, it was seen that the values were statistically significant at all the time intervals (P < 0.05. Conclusion: Dark chocolate had a high fall in pH and milk chocolate had low salivary sugar clearance which signifies that unfilled chocolates are more cariogenic than other chocolates. Even though mango-flavored candy had maximum fall in plaque pH, its salivary sugar clearance was high.

  11. pH modulation and salivary sugar clearance of different chocolates in children: A randomized clinical trial.

    Science.gov (United States)

    Nirmala, Svsg; Quadar, Mohammed Akhil; Veluru, Sindhuri

    2016-01-01

    Sugars that occur naturally in foods and those added in processed foods may act as the source for fermentable carbohydrates and may initiate caries process. Among all the foods consumed by children, chocolates form an important constituent. A wide variety of chocolates are available in the Indian market and very few studies have compared their acidogenicity and salivary sugar clearance. To compare the acidogenicity and salivary sugar clearance of 6 different commercially available chocolates in the Indian market. Thirty subjects aged 10-15 years were selected randomly from one of the available public schools in Nellore city. Six commercially available chocolates in the Indian market were divided into three groups, unfilled (dark and milk chocolate), filled (wafer and fruit and nuts chocolate), and candy (hard milk and mango-flavored candy) groups. Plaque pH values and salivary sugar clearance rates are assessed at baseline, 5, 10, 15, 20, and 30 min after consumption. All the data obtained were statistically evaluated using independent sample t-test and one-way ANOVA for multiple group comparisons. Mango-flavored candy had maximum fall in plaque pH and least fall in plaque pH was recorded with milk chocolate. Fruit and nuts chocolate had a maximum clearance of salivary sugar and least fall in the salivary sugar clearance was recorded with dark chocolate. When the plaque pH and salivary sugar clearance of all the chocolates were assessed, it was seen that the values were statistically significant at all the time intervals (P pH and milk chocolate had low salivary sugar clearance which signifies that unfilled chocolates are more cariogenic than other chocolates. Even though mango-flavored candy had maximum fall in plaque pH, its salivary sugar clearance was high.

  12. p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability

    Directory of Open Access Journals (Sweden)

    Giovanni Morelli

    2018-05-01

    Full Text Available Summary: The protein p27Kip1 plays roles that extend beyond cell-cycle regulation during cerebral cortex development, such as the regulation of neuronal migration and neurite branching via signaling pathways that converge on the actin and microtubule cytoskeletons. Microtubule-dependent transport is essential for the maturation of neurons and the establishment of neuronal connectivity though synapse formation and maintenance. Here, we show that p27Kip1 controls the transport of vesicles and organelles along the axon of mice cortical projection neurons in vitro. Moreover, suppression of the p27Kip1 ortholog, dacapo, in Drosophila melanogaster disrupts axonal transport in vivo, leading to the reduction of locomotor activity in third instar larvae and adult flies. At the molecular level, p27Kip1 stabilizes the α-tubulin acetyltransferase 1, thereby promoting the acetylation of microtubules, a post-translational modification required for proper axonal transport. : Morelli et al. report that p27Kip1/Dacapo modulates the acetylation of microtubules in axons via stabilization of ATAT1, the main α-tubulin acetyltransferase. Its conditional loss leads to the reduction of bidirectional axonal transport of vesicles and mitochondria in vitro in mice and in vivo in Drosophila. Keywords: p27Kip1, dacapo, acetylation, axonal transport, ATAT1, alpha-tubulin, HDAC6, Drosophila, mouse, cerebral cortex

  13. Modulation of small intestinal phosphate transporter by dietary supplements of mineral phosphorus and phytase in broilers.

    Science.gov (United States)

    Huber, Korinna; Zeller, Ellen; Rodehutscord, Markus

    2015-05-01

    Dietary phosphorus (P) is known as a main modulator of phosphate (Pi) transporter expression. The effect of supplemented mineral P with or without phytase on protein expression of two sodium-dependent Pi (NaPi) transporters and a calcium channel was studied in the small intestine of broilers. Thirty-six broilers were randomly assigned to six different diets at 15 days of age. Two levels of total P (tP, adjusted by monocalcium phosphate (MCP) supplementation), 0.39% (BD-) and 0.47% (BD+) were fed until day 25; and at each tP level, three levels of phytase were used with 0, 500, and 12,500 FTU/kg of an E. coli phytase. Mucosa samples from jejunum and ileum were taken and apical membranes were isolated by MgCl2 precipitation. Protein expression of NaPi IIb, NaPi type III (PiT1) and the calcium channel TRPV6 were semiquantitatively measured by Western blotting and jejunal mucosal phytase activity by measurement of Pi release. The jejunal NaPi IIb transporter was expressed with two distinct bands, which were modulated differently by diet. NaPi IIb Band1 increased (P phytase supplementation but was not affected by MCP supplementation. This inverse modulation of Band1 and Band2 was significantly related to the amount of net absorbed P with higher expression of Band1 at higher amounts of net absorbed P. In addition, a second Pi transporter, PiT1, was detected in which ileal expression decreased (P phytase supplementation. The expression of the calcium channel TRPV6 was increased in BD+ groups. A trend for an interaction between MCP and phytase supplementation on mucosal phytase activity was observed (P = 0.079) with a decrease in activity when BD+ with 12,500 FTU/kg phytase was fed. Chicken intestinal epithelial cells responded to dietary supplemented phytase and MCP by changing the Pi transporter expression in apical membranes. In conclusion, availability of Pi is most likely the key modulator of transporter protein expression. However, a contribution of lower inositol

  14. Modulating secretory pathway pH by proton channel co-expression can increase recombinant protein stability in plants.

    Science.gov (United States)

    Jutras, Philippe V; D'Aoust, Marc-André; Couture, Manon M-J; Vézina, Louis-Philippe; Goulet, Marie-Claire; Michaud, Dominique; Sainsbury, Frank

    2015-09-01

    Eukaryotic expression systems are used for the production of complex secreted proteins. However, recombinant proteins face considerable biochemical challenges along the secretory pathway, including proteolysis and pH variation between organelles. As the use of synthetic biology matures into solutions for protein production, various host-cell engineering approaches are being developed to ameliorate host-cell factors that can limit recombinant protein quality and yield. We report the potential of the influenza M2 ion channel as a novel tool to neutralize the pH in acidic subcellular compartments. Using transient expression in the plant host, Nicotiana benthamiana, we show that ion channel expression can significantly raise pH in the Golgi apparatus and that this can have a strong stabilizing effect on a fusion protein separated by an acid-susceptible linker peptide. We exemplify the utility of this effect in recombinant protein production using influenza hemagglutinin subtypes differentially stable at low pH; the expression of hemagglutinins prone to conformational change in mildly acidic conditions is considerably enhanced by M2 co-expression. The co-expression of a heterologous ion channel to stabilize acid-labile proteins and peptides represents a novel approach to increasing the yield and quality of secreted recombinant proteins in plants and, possibly, in other eukaryotic expression hosts. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Fermentation pH Modulates the Size Distributions and Functional Properties of Gluconobacter albidus TMW 2.1191 Levan

    Directory of Open Access Journals (Sweden)

    Tharalinee Ua-Arak

    2017-05-01

    Full Text Available Bacterial levan has gained an increasing interest over the last decades due to its unique characteristics and multiple possible applications. Levan and other exopolysaccharides (EPSs production are usually optimized to obtain the highest concentration or yield while a possible change of the molecular size and mass during the production process is mostly neglected. In this study, the molar mass and radius of levan samples were monitored during fermentations with the food-grade, levan-producing acetic acid bacterium Gluconobacter (G. albidus TMW 2.1191 in shake flasks (without pH control and bioreactors (with pH control at 4.5, 5.5 and 6.5, respectively. In uncontrolled fermentations, the levan size/molar mass continuously decreased concomitantly with the continuous acidification of the nutrient medium. On the contrary, the amount, molar mass and size of levan could be directly influenced by controlling the pH during fermentation. Using equal initial substrate amounts, the largest weight average molar mass and geometric radius of levan were observed at constant pH 6.5, while the highest levan concentration was obtained at constant pH 4.5. Since there is a special demand to find suitable hydrocolloids from food-grade bacteria to develop novel gluten-free (GF products, these differently produced levans were used for baking of GF breads, and the best quality improvement was obtained by addition of levan with the highest mass and radius. This work, therefore, demonstrates for the first time that one bacterial strain can produce specific high molecular weight fractions of one EPS type, which differ in properties and sizes among each other in dependence of the controllable production conditions.

  16. A plant-wide aqueous phase chemistry module describing pH variations and ion speciation/pairing in wastewater treatment process models

    DEFF Research Database (Denmark)

    Flores Alsina, Xavier; Kazadi Mbamba, Christian; Solon, Kimberly

    2015-01-01

    at different cationic/anionic loads. In this way, the general applicability/flexibility of the proposed approach is demonstrated, by implementing the aqueous phase chemistry module in some of the most frequently used WWTP process simulation models. Finally, it is shown how traditional wastewater modelling......, but unavoidable, additional degree of complexity when representing cationic/anionic behaviour in Activated Sludge (AS)/Anaerobic Digestion (AD) systems. In this paper, a plant-wide aqueous phase chemistry module describing pH variations plus ion speciation/pairing is presented and interfaced with industry......) in order to reduce the overall stiffness of the system, thereby enhancing simulation speed. Additionally, a multi-dimensional version of the Newton-Raphson algorithm is applied to handle the existing multiple algebraic inter-dependencies. The latter is reinforced with the Simulated Annealing method...

  17. External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor

    Science.gov (United States)

    Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K.; Shi, Yingtang; Wagner, Paul G.; Pivaroff-Ward, Kendra; Sassic, Jessica K.; Bayliss, Douglas A.

    2013-01-01

    The Ether-a-go-go (EAG) superfamily of voltage-gated K+ channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K+ currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K+ channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance–voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn2+. Low pH similarly reduces Mg2+ sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca2+. Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K+ currents observed in vivo. PMID:23712551

  18. External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor.

    Science.gov (United States)

    Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K; Shi, Yingtang; Wagner, Paul G; Pivaroff-Ward, Kendra; Sassic, Jessica K; Bayliss, Douglas A; Jegla, Timothy

    2013-06-01

    The Ether-a-go-go (EAG) superfamily of voltage-gated K(+) channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K(+) currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K(+) channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance-voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn(2+). Low pH similarly reduces Mg(2+) sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca(2+). Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K(+) currents observed in vivo.

  19. Testing of Streckeisen STS-5A and Nanometrics Trillium 120PH Sensors for the Alaska Transportable Array

    Science.gov (United States)

    Abbasi Baghbadorani, A.; Aderhold, K.; Bloomquist, D.; Frassetto, A.; Miller, P. E.; Busby, R. W.

    2017-12-01

    Starting in 2014, the IRIS Transportable Array facility began to install and operate seismic stations in Alaska and western Canada. By the end of the project, the full deployment of the array will cover a grid of 280 stations spaced about 85 km apart covering all of mainland Alaska and parts of the Yukon, British Columbia, and the Northwest Territories. Approximately 200 stations will be operated directly by IRIS through at least 2019. A key aspect of the Alaska TA is the need for stations to operate autonomously, on account of the high cost of installation and potential subsequent visits to remote field-sites to repair equipment. The TA is using newly developed broadband seismometers Streckeisen STS-5A and Nanometrics Trillium-120PH, designed for installation in shallow posthole emplacements. These new instruments were extensively vetted beforehand, but they are still relatively new to the TA inventory. Here we will assess their performance under deployment conditions and after repeated commercial shipping and travel to the field. Our objective is to provide a thorough accounting of the identified failures of the existing inventory of posthole instruments. We will assess the practices and results of instrument testing by the PASSCAL Instrument Center/Array Operations Facility (PIC/AOF), Alaska Operations Center (AOC), and broadband seismic sensor manufacturers (Streckeisen, Nanometrics) in order to document potential factors in and stages during the process for instrument failures. This will help to quantify the overall reliability of the TA seismic sensors and quality of TA practices and data collection, and identify potential considerations in future TA operations. Our results show that the overall rate of failure of all posthole instruments is improved station performance after sensor replacement, and that these are key elements in assessing whether or not a sensor should be replaced in the field.

  20. Increased NBCn1 expression, Na+/ HCO 3 ? co-transport and intracellular pH in human vascular smooth muscle cells with a risk allele for hypertension

    OpenAIRE

    Ng, Fu Liang; Boedtkjer, Ebbe; Witkowska, Kate; Ren, Meixia; Zhang, Ruoxin; Tucker, Arthur; Aalkj?r, Christian; Caulfield, Mark J.; Ye, Shu

    2017-01-01

    Abstract Genome-wide association studies have revealed an association between variation at the SLC4A7 locus and blood pressure. SLC4A7 encodes the electroneutral Na+/ HCO 3 ? co-transporter NBCn1 which regulates intracellular pH (pH i ). We conducted a functional study of variants at this locus in primary cultures of vascular smooth muscle and endothelial cells. In both cell types, we found genotype-dependent differences for rs13082711 in DNA-nuclear protein interactions, where the risk allel...

  1. Visualizing Carrier Transport in Metal Halide Perovskite Nanoplates via Electric Field Modulated Photoluminescence Imaging.

    Science.gov (United States)

    Hu, Xuelu; Wang, Xiao; Fan, Peng; Li, Yunyun; Zhang, Xuehong; Liu, Qingbo; Zheng, Weihao; Xu, Gengzhao; Wang, Xiaoxia; Zhu, Xiaoli; Pan, Anlian

    2018-05-09

    Metal halide perovskite nanostructures have recently been the focus of intense research due to their exceptional optoelectronic properties and potential applications in integrated photonics devices. Charge transport in perovskite nanostructure is a crucial process that defines efficiency of optoelectronic devices but still requires a deep understanding. Herein, we report the study of the charge transport, particularly the drift of minority carrier in both all-inorganic CsPbBr 3 and organic-inorganic hybrid CH 3 NH 3 PbBr 3 perovskite nanoplates by electric field modulated photoluminescence (PL) imaging. Bias voltage dependent elongated PL emission patterns were observed due to the carrier drift at external electric fields. By fitting the drift length as a function of electric field, we obtained the carrier mobility of about 28 cm 2 V -1 S -1 in the CsPbBr 3 perovskite nanoplate. The result is consistent with the spatially resolved PL dynamics measurement, confirming the feasibility of the method. Furthermore, the electric field modulated PL imaging is successfully applied to the study of temperature-dependent carrier mobility in CsPbBr 3 nanoplates. This work not only offers insights for the mobile carrier in metal halide perovskite nanostructures, which is essential for optimizing device design and performance prediction, but also provides a novel and simple method to investigate charge transport in many other optoelectronic materials.

  2. Analysis and modelling of power modulation experiments in JET plasmas with internal transport barriers

    Energy Technology Data Exchange (ETDEWEB)

    Marinoni, A [Politecnico di Milano, dipartimento di Ingegneria Nucleare, Milano (Italy); Mantica, P [Istituto di Fisica del Plasma, Euratom-ENEA-CNR Association, Milan (Italy); Eester, D Van [LPP-ERM/KMS, Association EURATOM-Belgian State, TEC, B-1000 Brussels (Belgium); Imbeaux, F [Association EURATOM-CEA, CEA/DSM/DRFC, CEA Cadarache, 13108 Saint Paul lez Durance (France); Mantsinen, M [Helsinki University of Technology, Association Euratom-Tekes, PO Box 2200 (Finland); Hawkes, N [Euratom-UKAEA Fusion Association, Culham Science Centre, Abingdon, Oxon (United Kingdom); Joffrin, E [Association EURATOM-CEA, CEA/DSM/DRFC, CEA Cadarache, 13108 Saint Paul lez Durance (France); Kiptily, V [Euratom-UKAEA Fusion Association, Culham Science Centre, Abingdon, Oxon (United Kingdom); Pinches, S D [Max Plank Institut fur Plasmaphysik, Euratom Association, Garching (Germany); Salmi, A [Helsinki University of Technology, Association Euratom-Tekes, PO Box 2200 (Finland); Sharapov, S [Euratom-UKAEA Fusion Association, Culham Science Centre, Abingdon, Oxon (United Kingdom); Voitsekhovitch, I [Euratom-UKAEA Fusion Association, Culham Science Centre, Abingdon, Oxon (United Kingdom); Vries, P de [FOM Institut voor Plasmafysica, Association Euratom-FOM, Nieuwegein, The (Netherlands); Zastrow, K D [Euratom-UKAEA Fusion Association, Culham Science Centre, Abingdon, Oxon (United Kingdom)

    2006-10-15

    Understanding the physics of internal transport barriers (ITBs) is a crucial issue in developing ITER relevant advanced tokamak scenarios. To gain new information on ITBs, RF power modulation experiments, mainly devoted to the study of electron heat transport through ITBs, have been performed on the JET tokamak. The main physics results have been reported in [1]. The present paper describes in detail the data analysis and numerical modelling work carried out for the interpretation of the experiments. ITBs located in the negative shear region behave as localized insulating layers able to stop the heat wave propagation, thus implying that the ITB is a region of low diffusivity characterized by a loss of stiffness. Various sources of spurious effects affecting the interpretation of the results are analysed and discussed. First principle based models have so far failed to predict the temperature profile in the first place, which prevented their application to modulation results, while empirical transport models have been set up and reproduce the major part of the data.

  3. Design of position monitor module in radioactive material transport monitoring system

    International Nuclear Information System (INIS)

    Adi Abimanyu; Dwi Yuliansari N

    2013-01-01

    Aspects of safety and security of radioactive substances from the sender to the receiver is to be secured so as not to harm humans. In general, monitoring is done through conversation by telephone to determine the location and rate of exposure of radioactive substances. Through the development of science and technology makes it possible to develop a system of monitoring the transport of radioactive substances in real time by combining radiation monitor module, position monitors module and sending information nir-cable. Position monitor module developed using GPS-receiver and a micro controller ATMega8 based serial interrupts communication. Testing is done by testing communication between micro controller and GPS and also testing reading position by GPS receiver. From the test results concluded that the developed modules is good in serial communication is based on serial interrupts, good position measurement to be used outdoors and is not good enough for measurements indoors because the GPS receiver used is not using an outdoor antenna. (author)

  4. A plant-wide aqueous phase chemistry module describing pH variations and ion speciation/pairing in wastewater treatment process models.

    Science.gov (United States)

    Flores-Alsina, Xavier; Kazadi Mbamba, Christian; Solon, Kimberly; Vrecko, Darko; Tait, Stephan; Batstone, Damien J; Jeppsson, Ulf; Gernaey, Krist V

    2015-11-15

    There is a growing interest within the Wastewater Treatment Plant (WWTP) modelling community to correctly describe physico-chemical processes after many years of mainly focusing on biokinetics. Indeed, future modelling needs, such as a plant-wide phosphorus (P) description, require a major, but unavoidable, additional degree of complexity when representing cationic/anionic behaviour in Activated Sludge (AS)/Anaerobic Digestion (AD) systems. In this paper, a plant-wide aqueous phase chemistry module describing pH variations plus ion speciation/pairing is presented and interfaced with industry standard models. The module accounts for extensive consideration of non-ideality, including ion activities instead of molar concentrations and complex ion pairing. The general equilibria are formulated as a set of Differential Algebraic Equations (DAEs) instead of Ordinary Differential Equations (ODEs) in order to reduce the overall stiffness of the system, thereby enhancing simulation speed. Additionally, a multi-dimensional version of the Newton-Raphson algorithm is applied to handle the existing multiple algebraic inter-dependencies. The latter is reinforced with the Simulated Annealing method to increase the robustness of the solver making the system not so dependent of the initial conditions. Simulation results show pH predictions when describing Biological Nutrient Removal (BNR) by the activated sludge models (ASM) 1, 2d and 3 comparing the performance of a nitrogen removal (WWTP1) and a combined nitrogen and phosphorus removal (WWTP2) treatment plant configuration under different anaerobic/anoxic/aerobic conditions. The same framework is implemented in the Benchmark Simulation Model No. 2 (BSM2) version of the Anaerobic Digestion Model No. 1 (ADM1) (WWTP3) as well, predicting pH values at different cationic/anionic loads. In this way, the general applicability/flexibility of the proposed approach is demonstrated, by implementing the aqueous phase chemistry module in some

  5. Cation modulation of hemoglobin interaction with sodium n-dodecyl sulphate (SDS iv: magnesium modulation at pH 7.20

    Directory of Open Access Journals (Sweden)

    Ali Akbar Moosavi-Movahedi

    2016-03-01

    Full Text Available We investigate the interaction of Mg2+ (0–2.30 mM and sodium n-dodecyl sulfate (SDS with hemoglobins (Hbs A and S at pH 7.20. SDS was used to model both membranes (0.60 mM SDS and proteases (5.0 mM SDS. Via UV-visible spectroscopy, second derivative and difference second derivative spectroscopy, we interrogated for difference(s in the interaction of these ligands with the proteins that can account for the HbS resistance to malaria parasite while been prone to sickling. Our results show that Mg2+ interaction with the proteins lowered the HbS oxygen affinity in comparison with the HbA. Additionally, [SDS]-protein interactions resulted in oxoferryl heme species formation that was prominent for the HbA and highly diminished for the HbS. [Mg2+] introduction to the [SDS]-protein mixture, however decreased the concentration of denatured protein species. The [Mg2+]-[SDS]-protein interactions suggest that while ionic or coulomb interactions for the HbA, in the presence of the surfactants, are [Mg2+] dependent, those of the HbS are not. Furthermore, hydrophobicity is a crucial force for the HbS interaction at neutral pH and is little-masked by ionic, electrostatic or coulombic interactions. In conclusion, at physiological pH, the Mg-SDS interaction decreased the HbS denaturation in comparison to the HbA.

  6. Dauer pheromone and G-protein signaling modulate the coordination of intraflagellar transport kinesin motor proteins in C. elegans

    NARCIS (Netherlands)

    J.A. Burghoorn (Jan); M.P.J. Dekkers (Martijn); S. Rademakers (Suzanne); A.A.W. de Jong (Ton); R. Willemsen (Rob); P. Swoboda (Peter); J. McCafferty (Gert)

    2010-01-01

    textabstractCilia length and function are dynamically regulated by modulation of intraflagellar transport (IFT). The cilia of C. elegans amphid channel neurons provide an excellent model to study this process, since they use two different kinesins for anterograde transport: kinesin-II and OSM-3

  7. New evidence and impact of electron transport non-linearities based on new perturbative inter-modulation analysis

    NARCIS (Netherlands)

    van Berkel, M.; Kobayashi, T.; Igami, H.; Vandersteen, Gerd; Hogeweij, G.M.D.; Tanaka, K.; Tamura, N.; Zwart, Hans; Kubo, S.; Ito, S.; Tsuchiya, H.; de Baar, M.R.

    2017-01-01

    A new methodology to analyze non-linear components in perturbative transport experiments is introduced. The methodology has been experimentally validated in the Large Helical Device for the electron heat transport channel. Electron cyclotron resonance heating with different modulation frequencies by

  8. Cation modulation of hemoglobin interaction with sodium n-dodecyl sulphate (SDS) iv: magnesium modulation at pH 7.20

    OpenAIRE

    Ali Akbar Moosavi-Movahedi; Ferdinand C. Chilaka; Charles O. Nwamba

    2016-01-01

    We investigate the interaction of Mg2+ (0–2.30 mM) and sodium n-dodecyl sulfate (SDS) with hemoglobins (Hbs) A and S at pH 7.20. SDS was used to model both membranes (0.60 mM SDS) and proteases (5.0 mM SDS). Via UV-visible spectroscopy, second derivative and difference second derivative spectroscopy, we interrogated for difference(s) in the interaction of these ligands with the proteins that can account for the HbS resistance to malaria parasite while been prone to sickling. Our results show ...

  9. Community production modulates coral reef pH and the sensitivity of ecosystem calcification to ocean acidification

    Science.gov (United States)

    DeCarlo, Thomas M.; Cohen, Anne L.; Wong, George T. F.; Shiah, Fuh-Kwo; Lentz, Steven J.; Davis, Kristen A.; Shamberger, Kathryn E. F.; Lohmann, Pat

    2017-01-01

    Coral reefs are built of calcium carbonate (CaCO3) produced biogenically by a diversity of calcifying plants, animals, and microbes. As the ocean warms and acidifies, there is mounting concern that declining calcification rates could shift coral reef CaCO3 budgets from net accretion to net dissolution. We quantified net ecosystem calcification (NEC) and production (NEP) on Dongsha Atoll, northern South China Sea, over a 2 week period that included a transient bleaching event. Peak daytime pH on the wide, shallow reef flat during the nonbleaching period was ˜8.5, significantly elevated above that of the surrounding open ocean (˜8.0-8.1) as a consequence of daytime NEP (up to 112 mmol C m-2 h-1). Diurnal-averaged NEC was 390 ± 90 mmol CaCO3 m-2 d-1, higher than any other coral reef studied to date despite comparable calcifier cover (25%) and relatively high fleshy algal cover (19%). Coral bleaching linked to elevated temperatures significantly reduced daytime NEP by 29 mmol C m-2 h-1. pH on the reef flat declined by 0.2 units, causing a 40% reduction in NEC in the absence of pH changes in the surrounding open ocean. Our findings highlight the interactive relationship between carbonate chemistry of coral reef ecosystems and ecosystem production and calcification rates, which are in turn impacted by ocean warming. As open-ocean waters bathing coral reefs warm and acidify over the 21st century, the health and composition of reef benthic communities will play a major role in determining on-reef conditions that will in turn dictate the ecosystem response to climate change.

  10. Electronic transport in armchair graphene nanoribbon under double magnetic barrier modulation

    Science.gov (United States)

    Wang, Haiyan; Wu, Chao; Xie, Fang; Zhang, Xiaojiao; Zhou, Guanghui

    2018-03-01

    We present a theoretical investigation of the transport properties and the magnetoresistance effect in armchair graphene nanoribbons (AGNRs) under modulation by two magnetic barriers. The energy levels are found to be degenerate for a metallic AGNR but are not degenerate for a semiconducting AGNR. However, the conductance characteristics show quantized plateaus in both the metallic and semiconducting cases. When the magnetization directions of the barriers change from parallel to antiparallel, the conductance plateau in the metallic AGNR shows a degenerate feature due to matching between the transport modes in different regions. As the barrier height increases, the conductance shows more oscillatory behavior with sharp peaks and troughs. Specifically, the initial position of nonzero conductance for the metallic AGNR system moves towards a higher energy regime, which indicates that an energy gap has been opened. In addition, the magnetoresistance ratio also shows plateau structures in certain specific energy regions. These results may be useful in the design of electron devices based on AGNR nanostructures.

  11. Recovery Of Chromium Metal (VI) Using Supported Liquid Membrane (SLM) Method, A study of Influence of NaCl and pH in Receiving Phase on Transport

    Science.gov (United States)

    Cholid Djunaidi, Muhammad; Lusiana, Retno A.; Rahayu, Maya D.

    2017-06-01

    Chromium metal(VI) is a valuable metal but in contrary has high toxicity, so the separation and recovery from waste are very important. One method that can be used for the separation and recovery of chromium (VI) is a Supported Liquid Membrane (SLM). SLM system contains of three main components: a supporting membrane, organic solvents and carrier compounds. The supported Membrane used in this research is Polytetrafluoroethylene (PTFE), organic solvent is kerosene, and the carrier compound used is aliquat 336. The supported liquid membrane is placed between two phases, namely, feed phase as the source of analyte (Cr(VI)) and the receiving phase as the result of separation. Feed phase is the electroplating waste which contains of chromium metal with pH variation about 4, 6 and 9. Whereas the receiving phase are the solution of HCl, NaOH, HCl-NaCl and NaOH-NaCl with pH variation about 1, 3, 5 and 7. The efficiency separation is determined by measurement of chromium in the feed and the receiving phase using AAS (Atomic Absorption Spectrophotometry). The experiment results show that transport of Chrom (VI) by Supported Liquid membrane (SLM) is influenced by pH solution in feed phase and receiving phase as well as NaCl in receiving phase. The highest chromium metal is transported from feed phase about 97,78%, whereas in receiving phase shows about 58,09%. The highest chromium metal transport happens on pH 6 in feed phase, pH 7 in receiving phase with the mixture of NaOH and NaCl using carrier compound aliquat 336.

  12. Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism.

    Science.gov (United States)

    Campion, Katherine L; McCormick, Wanda D; Warwicker, Jim; Khayat, Mohd Ezuan Bin; Atkinson-Dell, Rebecca; Steward, Martin C; Delbridge, Leigh W; Mun, Hee-Chang; Conigrave, Arthur D; Ward, Donald T

    2015-09-01

    The calcium-sensing receptor (CaR) modulates renal calcium reabsorption and parathyroid hormone (PTH) secretion and is involved in the etiology of secondary hyperparathyroidism in CKD. Supraphysiologic changes in extracellular pH (pHo) modulate CaR responsiveness in HEK-293 (CaR-HEK) cells. Therefore, because acidosis and alkalosis are associated with altered PTH secretion in vivo, we examined whether pathophysiologic changes in pHo can significantly alter CaR responsiveness in both heterologous and endogenous expression systems and whether this affects PTH secretion. In both CaR-HEK and isolated bovine parathyroid cells, decreasing pHo from 7.4 to 7.2 rapidly inhibited CaR-induced intracellular calcium (Ca(2+)i) mobilization, whereas raising pHo to 7.6 potentiated responsiveness to extracellular calcium (Ca(2+)o). Similar pHo effects were observed for Ca(2+)o-induced extracellular signal-regulated kinase phosphorylation and actin polymerization and for L-Phe-induced Ca(2+)i mobilization. Intracellular pH was unaffected by acute 0.4-unit pHo changes, and the presence of physiologic albumin concentrations failed to attenuate the pHo-mediated effects. None of the individual point mutations created at histidine or cysteine residues in the extracellular domain of CaR attenuated pHo sensitivity. Finally, pathophysiologic pHo elevation reversibly suppressed PTH secretion from perifused human parathyroid cells, and acidosis transiently increased PTH secretion. Therefore, pathophysiologic pHo changes can modulate CaR responsiveness in HEK-293 and parathyroid cells independently of extracellular histidine residues. Specifically, pathophysiologic acidification inhibits CaR activity, thus permitting PTH secretion, whereas alkalinization potentiates CaR activity to suppress PTH secretion. These findings suggest that acid-base disturbances may affect the CaR-mediated control of parathyroid function and calcium metabolism in vivo. Copyright © 2015 by the American Society of

  13. DMFC Module for non-road transport and mobile applications. Final report; DMFC Modul for intern transport og mobile anlaeg. Slutrapport

    Energy Technology Data Exchange (ETDEWEB)

    2008-04-15

    The objective of the project has been to develop a compact fuel cell generator using methanol as fuel. The DMFC module will be tested as power generator for internal transport using a Mini Crosser electric wheelchair for elderly and disabled people. The main advantage is the potential enhanced operation time (enhanced range) and the abbreviated recharge time compared with rechargeable batteries. The project approach was to use a hybrid system comprising a DMFC and a battery. The Hybrid system enables the usage of the battery to cover the dynamic power requirements while operating the DMFC generator at a constant load charging the battery. The project result is a functioning vehicle with a 600W DMFC system installed. The DMFC system has been tested independently and together with the vehicle where test results have been gathered. It was not possible within the project to make a compact installation in the existing battery box of the vehicle, but it is illustrated that it will be possible to make the full installation of a 2nd generation system in the vehicle. On the commercial side it is concluded that there can be a potential market entry opportunity if the DMFC system can meet commercialisation targets. It is also concluded that usage of a DMFC system in a closed wheel chair would give the possibility to use the produced heat from the fuel cell and thereby eliminate the requirement for an additional heater on the vehicle. (au)

  14. Ammonium ion transport by the AMT/Rh homolog TaAMT1;1 is stimulated by acidic pH

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Alsterfjord, Magnus; Macaulay, Nanna

    2009-01-01

    It is unclear how ammonia is transported by proteins from the Amt/Mep/Rh superfamily. We investigated this for the ammonium transporter TaAMT1;1 from wheat expressed in Xenopus oocytes by two-electrode voltage clamp and radio-labeled uptakes. Inward currents were activated by NH (4......) (+) or methylammonium ions (MeA(+)). Importantly, currents increased fivefold when the external pH was decreased from 7.4 to 5.5; this type of pH dependence is unique and is a strong indication of NH (4) (+) or MeA(+) transport. This was confirmed by the close correlation between the uptake of radio-labeled Me......A(+) and MeA(+)-induced currents. Homology models of members of the Amt/Mep/Rh superfamily exhibited major divergences in their cytoplasmic regions. A point mutation in this region of TaAMT1;1 abolished the pH sensitivity and decreased the apparent affinities for NH (4) (+) and MeA(+). We suggest a model...

  15. Dopamine transporter polymorphism modulates oculomotor function and DAT1 mRNA expression in schizophrenia.

    Science.gov (United States)

    Wonodi, Ikwunga; Hong, L Elliot; Stine, O Colin; Mitchell, Braxton D; Elliott, Amie; Roberts, Rosalinda C; Conley, Robert R; McMahon, Robert P; Thaker, Gunvant K

    2009-03-05

    Smooth pursuit eye movement (SPEM) deficit is an established schizophrenia endophenotype with a similar neurocognitive construct to working memory. Frontal eye field (FEF) neurons controlling SPEM maintain firing when visual sensory information is removed, and their firing rates directly correlate with SPEM velocity. We previously demonstrated a paradoxical association between a functional polymorphism of dopamine signaling (COMT gene) and SPEM. Recent evidence implicates the dopamine transporter gene (DAT1) in modulating cortical dopamine and associated neurocognitive functions. We hypothesized that DAT1 10/10 genotype, which reduces dopamine transporter expression and increases extracellular dopamine, would affect SPEM. We examined the effects of DAT1 genotype on: Clinical diagnosis in the study sample (n = 418; 190 with schizophrenia), SPEM measures in a subgroup with completed oculomotor measures (n = 200; 87 schizophrenia), and DAT1 gene expression in FEF tissue obtained from postmortem brain samples (n = 32; 16 schizophrenia). DAT1 genotype was not associated with schizophrenia. DAT1 10/10 genotype was associated with better SPEM in healthy controls, intermediate SPEM in unaffected first-degree relatives of schizophrenia subjects, and worse SPEM in schizophrenia subjects. In the gene expression study, DAT1 10/10 genotype was associated with significantly reduced DAT1 mRNA transcript in FEF tissue from healthy control donors (P < 0.05), but higher expression in schizophrenia donors. Findings suggest regulatory effects of another gene(s) or etiological factor in schizophrenia, which modulate DAT1 gene function. 2008 Wiley-Liss, Inc.

  16. Directed transport in a periodic tube driven by asymmetric unbiased forces coexisting with spatially modulated noises

    International Nuclear Information System (INIS)

    Li Fengguo; Ai Baoquan

    2011-01-01

    Graphical abstract: The current J as a function of the phase shift φ and ε at a = 1/2π, b = 0.5/2π, k B T = 0.5, α = 0.1, and F 0 = 0.5. Highlights: → Unbiased forces and spatially modulated white noises affect the current. → In the adiabatic limit, the analytical expression of directed current is obtained. → Their competition will induce current reversals. → For negative asymmetric parameters of the force, there exists an optimum parameter. → The current increases monotonously for positive asymmetric parameters. - Abstract: Transport of Brownian particles in a symmetrically periodic tube is investigated in the presence of asymmetric unbiased external forces and spatially modulated Gaussian white noises. In the adiabatic limit, we obtain the analytical expression of the directed current. It is found that the temporal asymmetry can break thermodynamic equilibrium and induce a net current. Their competition between the temporal asymmetry force and the phase shift between the noise modulation and the tube shape will induce some peculiar phenomena, for example, current reversals. The current changes with the phase shift in the form of the sine function. For negative asymmetric parameters of the force, there exists an optimum parameter at which the current takes its maximum value. However, the current increases monotonously for positive asymmetric parameters.

  17. Ferromagnetic-insulators-modulated transport properties on the surface of a topological insulator

    International Nuclear Information System (INIS)

    Guo Jun-Ji; Liao Wen-Hu

    2014-01-01

    Transport properties on the surface of a topological insulator (TI) under the modulation of a two-dimensional (2D) ferromagnet/ferromagnet junction are investigated by the method of wave function matching. The single ferromagnetic barrier modulated transmission probability is expected to be a periodic function of the polarization angle and the planar rotation angle, that decreases with the strength of the magnetic proximity exchange increasing. However, the transmission probability for the double ferromagnetic insulators modulated n—n junction and n—p junction is not a periodic function of polarization angle nor planar rotation angle, owing to the combined effects of the double ferromagnetic insulators and the barrier potential. Since the energy gap between the conduction band and the valence band is narrowed and widened respectively in ranges of 0 ≤ θ < π/2 and π/2 < θ ≤ π, the transmission probability of the n—n junction first increases rapidly and then decreases slowly with the increase of the magnetic proximity exchange strength. While the transmission probability for the n—p junction demonstrates an opposite trend on the strength of the magnetic proximity exchange because the band gaps contrarily vary. The obtained results may lead to the possible realization of a magnetic/electric switch based on TIs and be useful in further understanding the surface states of TIs

  18. Glutamate modulation of GABA transport in retinal horizontal cells of the skate

    Science.gov (United States)

    Kreitzer, Matthew A; Andersen, Kristen A; Malchow, Robert Paul

    2003-01-01

    Transport of the amino acid GABA into neurons and glia plays a key role in regulating the effects of GABA in the vertebrate retina. We have examined the modulation of GABA-elicited transport currents of retinal horizontal cells by glutamate, the likely neurotransmitter of vertebrate photoreceptors. Enzymatically isolated external horizontal cells of skate were examined using whole-cell voltage-clamp techniques. GABA (1 mm) elicited an inward current that was completely suppressed by the GABA transport inhibitors tiagabine (10 μm) and SKF89976-A (100 μm), but was unaffected by 100 μm picrotoxin. Prior application of 100 μm glutamate significantly reduced the GABA-elicited current. Glutamate depressed the GABA dose-response curve without shifting the curve laterally or altering the voltage dependence of the current. The ionotropic glutamate receptor agonists kainate and AMPA also reduced the GABA-elicited current, and the effects of glutamate and kainate were abolished by the ionotropic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline. NMDA neither elicited a current nor modified the GABA-induced current, and metabotropic glutamate analogues were also without effect. Inhibition of the GABA-elicited current by glutamate and kainate was reduced when extracellular calcium was removed and when recording pipettes contained high concentrations of the calcium chelator BAPTA. Caffeine (5 mm) and thapsigargin (2 nm), agents known to alter intracellular calcium levels, also reduced the GABA-elicited current, but increases in calcium induced by depolarization alone did not. Our data suggest that glutamate regulates GABA transport in retinal horizontal cells through a calcium-dependent process, and imply a close physical relationship between calcium-permeable glutamate receptors and GABA transporters in these cells. PMID:12562999

  19. Modulation and Control of Charge Transport Through Single-Molecule Junctions.

    Science.gov (United States)

    Wang, Kun; Xu, Bingqian

    2017-02-01

    The ability to modulate and control charge transport though single-molecule junction devices is crucial to achieving the ultimate goal of molecular electronics: constructing real-world-applicable electronic components from single molecules. This review aims to highlight the progress made in single-molecule electronics, emphasizing the development of molecular junction electronics in recent years. Among many techniques that attempt to wire a molecule to metallic electrodes, the single-molecule break junction (SMBJ) technique is one of the most reliable and tunable experimental platforms for achieving metal-molecule-metal configurations. It also provides great freedom to tune charge transport through the junction. Soon after the SMBJ technique was introduced, it was extensively used to measure the conductances of individual molecules; however, different conductances were obtained for the same molecule, and it proved difficult to interpret this wide distribution of experimental data. This phenomenon was later found to be mainly due to a lack of precise experimental control and advanced data analysis methods. In recent years, researchers have directed considerable effort into advancing the SMBJ technique by gaining a deeper physical understanding of charge transport through single molecules and thus enhancing its potential applicability in functional molecular-scale electronic devices, such as molecular diodes and molecular transistors. In parallel with that research, novel data analysis methods and approaches that enable the discovery of hidden yet important features in the data are being developed. This review discusses various aspects of molecular junction electronics, from the initial goal of molecular electronics, the development of experimental techniques for creating single-molecule junctions and determining single-molecule conductance, to the characterization of functional current-voltage features and the investigation of physical properties other than charge

  20. Identification and modulation of the key amino acid residue responsible for the pH sensitivity of neoculin, a taste-modifying protein.

    Directory of Open Access Journals (Sweden)

    Ken-ichiro Nakajima

    Full Text Available Neoculin occurring in the tropical fruit of Curculigo latifolia is currently the only protein that possesses both a sweet taste and a taste-modifying activity of converting sourness into sweetness. Structurally, this protein is a heterodimer consisting of a neoculin acidic subunit (NAS and a neoculin basic subunit (NBS. Recently, we found that a neoculin variant in which all five histidine residues are replaced with alanine elicits intense sweetness at both neutral and acidic pH but has no taste-modifying activity. To identify the critical histidine residue(s responsible for this activity, we produced a series of His-to-Ala neoculin variants and evaluated their sweetness levels using cell-based calcium imaging and a human sensory test. Our results suggest that NBS His11 functions as a primary pH sensor for neoculin to elicit taste modification. Neoculin variants with substitutions other than His-to-Ala were further analyzed to clarify the role of the NBS position 11 in the taste-modifying activity. We found that the aromatic character of the amino acid side chain is necessary to elicit the pH-dependent sweetness. Interestingly, since the His-to-Tyr variant is a novel taste-modifying protein with alternative pH sensitivity, the position 11 in NBS can be critical to modulate the pH-dependent activity of neoculin. These findings are important for understanding the pH-sensitive functional changes in proteinaceous ligands in general and the interaction of taste receptor-taste substance in particular.

  1. Electron transport due to inhomogeneous broadening and its potential impact on modulation speed in p-doped quantum dot lasers

    International Nuclear Information System (INIS)

    Deppe, D G; Freisem, S; Huang, H; Lipson, S

    2005-01-01

    Data are first presented on spontaneous and laser emission of p-doped and undoped quantum dot (QD) heterostructures to characterize the increase in optical gain in p-type modulation doped QD lasers. Because the increase in gain due to p-doping should also increase the differential gain, but does not greatly increase the modulation speed in present p-doped QD lasers, we further examine nonequilibrium electron transport effects in p-doped active material that may still limit the modulation speed. Electron transport through the dot wetting layer caused by the nonlasing QDs of the active ensemble is shown to be capable of substantially reducing the modulation speed, independent of the differential gain. This nonequilibrium limitation can be eliminated by reducing the inhomogeneous broadening in the QD ensemble

  2. Effects of starvation on the transport of Escherichia coli K12 in saturated porous media are dependent on pH and ionic strength

    Science.gov (United States)

    Xu, S.; Walczak, J. J.; Wang, L.; Bardy, S. L.; Li, J.

    2010-12-01

    In this research, we investigate the effects of starvation on the transport of E. coli K12 in saturated porous media. Particularly, we examine the relationship between such effects and the pH and ionic strength of the electrolyte solutions that were used to suspend bacterial cells. E. coli K12 (ATCC 10798) cells were cultured using either Luria-Bertani Miller (LB-Miller) broth (10 g trypton, 5 g yeast extract and 10 g NaCl in 1 L of deionized water) or LB-Luria broth (10 g tryptone, 5 g yeast extract and 0.5 g NaCl in 1 L of deionized water). Both broths had similar pH (~7.1) but differed in ionic strength (LB-Miller: ~170 mM, LB-Luria: ~ 8 mM). The bacterial cells were then harvested and suspended using one of the following electrolyte solutions: phosphate buffered saline (PBS) (pH ~7.2; ionic strength ~170 mM), 168 mM NaCl (pH ~5.7), 5% of PBS (pH ~ 7.2; ionic strength ~ 8 mM) and 8 mM NaCl (pH ~ 5.7). Column transport experiments were performed at 0, 21 and 48 hours following cell harvesting to evaluate the change in cell mobility over time under “starvation” conditions. Our results showed that 1) starvation increased the mobility of E. coli K12 cells; 2) the most significant change in mobility occurred when bacterial cells were suspended in an electrolyte solution that had different pH and ionic strength (i.e., LB-Miller culture suspended in 8 mM NaCl and LB-Luria culture suspended in 168 mM Nacl); and 3) the change in cell mobility primarily occurred within the first 21 hours. The size of the bacterial cells was measured and the surface properties (e.g., zeta potential, hydrophobicity, cell-bound protein, LPS sugar content, outer membrane protein profiles) of the bacterial cells were characterized. We found that the measured cell surface properties could not fully explain the observed changes in cell mobility caused by starvation.

  3. Dispersed solar thermal generation employing parabolic dish-electric transport with field modulated generator systems

    Science.gov (United States)

    Ramakumar, R.; Bahrami, K.

    1981-01-01

    This paper discusses the application of field modulated generator systems (FMGS) to dispersed solar-thermal-electric generation from a parabolic dish field with electric transport. Each solar generation unit is rated at 15 kWe and the power generated by an array of such units is electrically collected for insertion into an existing utility grid. Such an approach appears to be most suitable when the heat engine rotational speeds are high (greater than 6000 r/min) and, in particular, if they are operated in the variable speed mode and if utility-grade a.c. is required for direct insertion into the grid without an intermediate electric energy storage and reconversion system. Predictions of overall efficiencies based on conservative efficiency figures for the FMGS are in the range of 25 per cent and should be encouraging to those involved in the development of cost-effective dispersed solar thermal power systems.

  4. Modulator considerations for beam chopping in the low energy beam transport at the SSC Laboratory

    International Nuclear Information System (INIS)

    Anderson, D.; Pappas, G.

    1991-06-01

    Beam chopping in the low energy transport line at the Superconducting Super Collider Laboratory is accomplished using an electrostatic deflection system. LINAC requirements dictate the design of two modulators operating at 10 Hz with rise and fall times (as measured from approximately 10--99%) of ∼100 ns. Design of the first pulser, normally at 10 kV and pulsed to ground potential, utilizes a transformer-coupled diode-clamped solid state circuit to achieve the 2--35 μs pulse width range required. The second pulser, which pulses from ground to approximately 7 kV, relies on a series vacuum tube circuit. The current designs, as well as recent test results and other circuit topologies considered, will be presented. 6 refs

  5. Key scattering mechanisms limiting the lateral transport in a modulation-doped polar heterojunction

    Energy Technology Data Exchange (ETDEWEB)

    Tien, Nguyen Thanh, E-mail: nttien@ctu.edu.vn; Thao, Pham Thi Bich [College of Natural Sciences, Can Tho University, 3-2 Road, Can Tho City (Viet Nam); Thao, Dinh Nhu [Center for Theoretical and Computational Physics, College of Education, Hue University, 34 Le Loi Street, Hue City (Viet Nam); Quang, Doan Nhat [Institute of Physics, Vietnamese Academy of Science and Technology, 10 Dao Tan Street, Hanoi (Viet Nam)

    2016-06-07

    We present a study of the lateral transport of a two-dimensional electron gas (2DEG) in a modulation-doped polar heterojunction (HJ). In contrast to previous studies, we assume that the Coulomb correlation among ionized impurities and among charged dislocations in the HJ is so strong that the 2DEG low-temperature mobility is not limited by impurity and dislocation scattering. The mobility, however, is specified by alloy disorder scattering and combined roughness scattering, which is the total effect induced by both the potential barrier and polarization roughness. The obtained results show that the alloy disorder and combined roughness scattering strongly depend on the alloy content and on the near-interface electron distribution. Our theory is capable of explaining the bell-shaped dependence of the lateral mobility on alloy content observed in AlGaN/GaN and on 2DEG density observed in AlN/GaN, which have not previously been explained.

  6. Two cation transporters Ena1 and Nha1 cooperatively modulate ion homeostasis, antifungal drug resistance, and virulence of Cryptococcus neoformans via the HOG pathway

    Science.gov (United States)

    Jung, Kwang-Woo; Strain, Anna K; Nielsen, Kirsten; Jung, Kwang-Hwan; Bahn, Yong-Sun

    2012-01-01

    Maintenance of cation homeostasis is essential for survival of all living organisms in their biological niches. It is also important for the survival of human pathogenic fungi in the host, where cation concentrations and pH will vary depending on different anatomical sites. However, the exact role of diverse cation transporters and ion channels in virulence of fungal pathogens remains elusive. In this study we functionally characterized ENA1 and NHA1, encoding a putative Na+/ATPase and Na+/H+ antiporter, respectively, in Cryptococcus neoformans, a basidiomycete fungal pathogen which causes fatal meningoencephalitis. Expression of NHA1 and ENA1 is induced in response to salt and osmotic shock mainly in a Hog1-dependent manner. Phenotypic analysis of the ena1, nha1, and ena1 nha1 mutants revealed that Ena1 controls cellular levels of toxic cations, such as Na+ and Li+ whereas both Ena1 and Nha1 are important for controlling less toxic K+ ions. Under alkaline conditions, Ena1 was highly induced and required for growth in the presence of low levels of Na+ or K+ salt and Nha1 played a role in survival under K+ stress. In contrast, Nha1, but not Ena1, was essential for survival at acidic conditions (pH 4.5) under high K+ stress. In addition, Ena1 and Nha1 were required for maintenance of plasma membrane potential and stability, which appeared to modulate antifungal drug susceptibility. Perturbation of ENA1 and NHA1 enhanced capsule production and melanin synthesis. However, Nha1 was dispensable for virulence of C. neoformans although Ena1 was essential. In conclusion, Ena1 and Nha1 play redundant and discrete roles in cation homeostasis, pH regulation, membrane potential, and virulence in C. neoformans, suggesting that these transporters could be novel antifungal drug targets for treatment of cryptococcosis. PMID:22343280

  7. Transport properties in a monolayer graphene modulated by the realistic magnetic field and the Schottky metal stripe

    Science.gov (United States)

    Lu, Jian-Duo; Li, Yun-Bao; Liu, Hong-Yu; Peng, Shun-Jin; Zhao, Fei-Xiang

    2016-09-01

    Based on the transfer-matrix method, a systematic investigation of electron transport properties is done in a monolayer graphene modulated by the realistic magnetic field and the Schottky metal stripe. The strong dependence of the electron transmission and the conductance on the incident angle of carriers is clearly seen. The height, position as well as width of the barrier also play an important role on the electron transport properties. These interesting results are very useful for understanding the tunneling mechanism in the monolayer graphene and helpful for designing the graphene-based electrical device modulated by the realistic magnetic field and the electrical barrier.

  8. Dendrimer nanocarriers for transport modulation across models of the pulmonary epithelium.

    Science.gov (United States)

    Bharatwaj, Balaji; Mohammad, Abdul Khader; Dimovski, Radovan; Cassio, Fernando L; Bazito, Reinaldo C; Conti, Denise; Fu, Qiang; Reineke, Joshua; da Rocha, Sandro R P

    2015-03-02

    The purpose of this study was to determine the effect of PEGylation on the interaction of poly(amidoamine) (PAMAM) dendrimer nanocarriers (DNCs) with in vitro and in vivo models of the pulmonary epithelium. Generation-3 PAMAM dendrimers with varying surface densities of PEG 1000 Da were synthesized and characterized. The results revealed that the apical to basolateral transport of DNCs across polarized Calu-3 monolayers increases with an increase in PEG surface density. DNC having the greatest number of PEG groups (n = 25) on their surface traversed at a rate 10-fold greater than its non-PEGylated counterpart, in spite of their larger size. This behavior was attributed to a significant reduction in charge density upon PEGylation. We also observed that PEGylation can be used to modulate cellular internalization. The total uptake of PEG-free DNC into polarized Calu-3 monolayers was 12% (w/w) vs 2% (w/w) for that with 25 PEGs. Polarization is also shown to be of great relevance in studying this in vitro model of the lung epithelium. The rate of absorption of DNCs administered to mice lungs increased dramatically when conjugated with 25 PEG groups, thus supporting the in vitro results. The exposure obtained for the DNC with 25PEG was determined to be very high, with peak plasma concentrations reaching 5 μg·mL(-1) within 3 h. The combined in vitro and in vivo results shown here demonstrate that PEGylation can be potentially used to modulate the internalization and transport of DNCs across the pulmonary epithelium. Modified dendrimers thereby may serve as a valuable platform that can be tailored to target the lung tissue for treating local diseases, or the circulation, using the lung as pathway to the bloodstream, for systemic delivery.

  9. Mode-selective vibrational modulation of charge transport in organic electronic devices

    KAUST Repository

    Bakulin, Artem A.; Lovrincic, Robert; Yu, Xi; Selig, Oleg; Bakker, Huib J.; Rezus, Yves L. A.; Nayak, Pabitra K.; Fonari, Alexandr; Coropceanu, Veaceslav; Bredas, Jean-Luc; Cahen, David

    2015-01-01

    The soft character of organic materials leads to strong coupling between molecular, nuclear and electronic dynamics. This coupling opens the way to influence charge transport in organic electronic devices by exciting molecular vibrational motions. However, despite encouraging theoretical predictions, experimental realization of such approach has remained elusive. Here we demonstrate experimentally that photoconductivity in a model organic optoelectronic device can be modulated by the selective excitation of molecular vibrations. Using an ultrafast infrared laser source to create a coherent superposition of vibrational motions in a pentacene/C60 photoresistor, we observe that excitation of certain modes in the 1,500–1,700 cm−1 region leads to photocurrent enhancement. Excited vibrations affect predominantly trapped carriers. The effect depends on the nature of the vibration and its mode-specific character can be well described by the vibrational modulation of intermolecular electronic couplings. This presents a new tool for studying electron–phonon coupling and charge dynamics in (bio)molecular materials.

  10. Mode-selective vibrational modulation of charge transport in organic electronic devices

    KAUST Repository

    Bakulin, Artem A.

    2015-08-06

    The soft character of organic materials leads to strong coupling between molecular, nuclear and electronic dynamics. This coupling opens the way to influence charge transport in organic electronic devices by exciting molecular vibrational motions. However, despite encouraging theoretical predictions, experimental realization of such approach has remained elusive. Here we demonstrate experimentally that photoconductivity in a model organic optoelectronic device can be modulated by the selective excitation of molecular vibrations. Using an ultrafast infrared laser source to create a coherent superposition of vibrational motions in a pentacene/C60 photoresistor, we observe that excitation of certain modes in the 1,500–1,700 cm−1 region leads to photocurrent enhancement. Excited vibrations affect predominantly trapped carriers. The effect depends on the nature of the vibration and its mode-specific character can be well described by the vibrational modulation of intermolecular electronic couplings. This presents a new tool for studying electron–phonon coupling and charge dynamics in (bio)molecular materials.

  11. Nanoscale phase engineering of thermal transport with a Josephson heat modulator

    Science.gov (United States)

    Fornieri, Antonio; Blanc, Christophe; Bosisio, Riccardo; D'Ambrosio, Sophie; Giazotto, Francesco

    2016-03-01

    Macroscopic quantum phase coherence has one of its pivotal expressions in the Josephson effect, which manifests itself both in charge and energy transport. The ability to master the amount of heat transferred through two tunnel-coupled superconductors by tuning their phase difference is the core of coherent caloritronics, and is expected to be a key tool in a number of nanoscience fields, including solid-state cooling, thermal isolation, radiation detection, quantum information and thermal logic. Here, we show the realization of the first balanced Josephson heat modulator designed to offer full control at the nanoscale over the phase-coherent component of thermal currents. Our device provides magnetic-flux-dependent temperature modulations up to 40 mK in amplitude with a maximum of the flux-to-temperature transfer coefficient reaching 200 mK per flux quantum at a bath temperature of 25 mK. Foremost, it demonstrates the exact correspondence in the phase engineering of charge and heat currents, breaking ground for advanced caloritronic nanodevices such as thermal splitters, heat pumps and time-dependent electronic engines.

  12. Development of CAD-Based Geometry Processing Module for a Monte Carlo Particle Transport Analysis Code

    International Nuclear Information System (INIS)

    Choi, Sung Hoon; Kwark, Min Su; Shim, Hyung Jin

    2012-01-01

    As The Monte Carlo (MC) particle transport analysis for a complex system such as research reactor, accelerator, and fusion facility may require accurate modeling of the complicated geometry. Its manual modeling by using the text interface of a MC code to define the geometrical objects is tedious, lengthy and error-prone. This problem can be overcome by taking advantage of modeling capability of the computer aided design (CAD) system. There have been two kinds of approaches to develop MC code systems utilizing the CAD data: the external format conversion and the CAD kernel imbedded MC simulation. The first approach includes several interfacing programs such as McCAD, MCAM, GEOMIT etc. which were developed to automatically convert the CAD data into the MCNP geometry input data. This approach makes the most of the existing MC codes without any modifications, but implies latent data inconsistency due to the difference of the geometry modeling system. In the second approach, a MC code utilizes the CAD data for the direct particle tracking or the conversion to an internal data structure of the constructive solid geometry (CSG) and/or boundary representation (B-rep) modeling with help of a CAD kernel. MCNP-BRL and OiNC have demonstrated their capabilities of the CAD-based MC simulations. Recently we have developed a CAD-based geometry processing module for the MC particle simulation by using the OpenCASCADE (OCC) library. In the developed module, CAD data can be used for the particle tracking through primitive CAD surfaces (hereafter the CAD-based tracking) or the internal conversion to the CSG data structure. In this paper, the performances of the text-based model, the CAD-based tracking, and the internal CSG conversion are compared by using an in-house MC code, McSIM, equipped with the developed CAD-based geometry processing module

  13. Diffusive-to-ballistic transition of the modulated heat transport in a rarefied air chamber

    Directory of Open Access Journals (Sweden)

    C. L. Gomez-Heredia

    2017-01-01

    Full Text Available Modulated heat transfer in air subject to pressures from 760 Torr to 10-4 Torr is experimentally studied by means of a thermal-wave resonant cavity placed in a vacuum chamber. This is done through the analysis of the amplitude and phase delay of the photothermal signal as a function of the cavity length and pressure through of the Knudsen’s number. The viscous, transitional, and free molecular regimes of heat transport are observed for pressures P>1.5 Torr, 25 mTorrtransport.

  14. Aging Selectively Modulates Vitamin C Transporter Expression Patterns in the Kidney.

    Science.gov (United States)

    Forman, Katherine; Martínez, Fernando; Cifuentes, Manuel; Bertinat, Romina; Salazar, Katterine; Nualart, Francisco

    2017-09-01

    In the kidney, vitamin C is reabsorbed from the glomerular ultrafiltrate by sodium-vitamin C cotransporter isoform 1 (SVCT1) located in the brush border membrane of the proximal tubules. Although we know that vitamin C levels decrease with age, the adaptive physiological mechanisms used by the kidney for vitamin C reabsorption during aging remain unknown. In this study, we used an animal model of accelerated senescence (SAMP8 mice) to define the morphological alterations and aging-induced changes in the expression of vitamin C transporters in renal tissue. Aging induced significant morphological changes, such as periglomerular lymphocytic infiltrate and glomerular congestion, in the kidneys of SAMP8 mice, although no increase in collagen deposits was observed using 2-photon microscopy analysis and second harmonic generation. The most characteristic histological alteration was the dilation of intracellular spaces in the basolateral region of proximal tubule epithelial cells. Furthermore, a combination of laser microdissection, qRT-PCR, and immunohistochemical analyses allowed us to determine that SVCT1 expression specifically increased in the proximal tubules from the outer strip of the outer medulla (segment S3) and cortex (segment S2) during aging and that these tubules also express GLUT1. We conclude that aging modulates vitamin C transporter expression and that renal over-expression of SVCT1 enhances vitamin C reabsorption in aged animals that may synthesize less vitamin C. J. Cell. Physiol. 232: 2418-2426, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Disulfiram is a potent modulator of multidrug transporter Cdr1p of Candida albicans

    International Nuclear Information System (INIS)

    Shukla, Suneet; Sauna, Zuben E.; Prasad, Rajendra; Ambudkar, Suresh V.

    2004-01-01

    To find novel drugs for effective antifungal therapy in candidiasis, we examined disulfiram, a drug used for the treatment of alcoholism, for its role as a potential modulator of Candida multidrug transporter Cdr1p. We show that disulfiram inhibits the oligomycin-sensitive ATPase activity of Cdr1p and 2.5 mM dithiothreitol reverses this inhibition. Disulfiram inhibited the binding of photoaffinity analogs of both ATP ([α- 32 P]8-azidoATP; IC 50 = 0.76 μM) and drug-substrates ([ 3 H]azidopine and [ 125 I]iodoarylazidoprazosin; IC 50 ∼ 12 μM) to Cdr1p in a concentration-dependent manner, suggesting that it can interact with both ATP and substrate-binding site(s) of Cdr1p. Furthermore, a non-toxic concentration of disulfiram (1 μM) increased the sensitivity of Cdr1p expressing Saccharomyces cerevisiae cells to antifungal agents (fluconazole, miconazole, nystatin, and cycloheximide). Collectively these results demonstrate that disulfiram reverses Cdr1p-mediated drug resistance by interaction with both ATP and substrate-binding sites of the transporter and may be useful for antifungal therapy

  16. NFκBP65 transcription factor modulates resistance to doxorubicin through ABC transporters in breast cancer.

    Science.gov (United States)

    Velaei, Kobra; Samadi, Nasser; Soltani, Sina; Barazvan, Balal; Soleimani Rad, Jafar

    2017-07-01

    Shedding light on chemoresistance biology of breast cancer could contribute to enhance the clinical outcome. Intrinsic or acquired resistance to chemotherapy is a major problem in breast cancer treatment. The NFκB pathway by siRNAP65 and JSH-23 as a translocational inhibitor of NFκBP65 in the doxorubicin-resistant MCF-7 (MCF-7/Dox) and MCF-7 cells was blocked. Then, the ABC transporter expression and function were assessed by real-time qRT-PCR and flow cytometry, respectively. Induction of apoptosis was evaluated after inhibition of the NFΚB pathway as well. Our study underlined the upregulation of NFκBP65 and anti-apoptotic Bcl-2 and downregulation of pro-apoptotic Bax in the MCF-7/Dox cells compared with control MCF-7 cells. Here, we showed that interplay between nuclear factor kappa B P65 (NFkBP65) as a transcriptional regulator and ABC transporters in the MCF-7/Dox cancer cells. We found that inhibition of the elevated expression of NFκBP65 in the resistant breast cancer, whether translocational inhibition or silencing by siRNA, decreased the expression and function of MDR1 and MRP1 efflux pumps. Furthermore, the blockade of NFκBP65 promoted apoptosis via modulating Bcl-2 and BAX expression. After inhibition of the NFκBP65 signaling pathway, elevated baseline expression of survival Bcl-2 gene in the resistant breast cells significantly decreased. Suppression of the NFκB pathway has a profound dual impact on promoting the intrinsic apoptotic pathway and reducing ABC transporter function and expression, which are some of the chemoresistance features. It was speculated that the NFκB pathway directly acts on doxorubicin-induced MDR1 and MRP1 expression in MCF-7/Dox cells.

  17. Transintestinal transport of the anti-inflammatory drug 4F and the modulation of transintestinal cholesterol efflux[S

    Science.gov (United States)

    Meriwether, David; Sulaiman, Dawoud; Wagner, Alan; Grijalva, Victor; Kaji, Izumi; Williams, Kevin J.; Yu, Liqing; Fogelman, Spencer; Volpe, Carmen; Bensinger, Steven J.; Anantharamaiah, G. M.; Shechter, Ishaiahu; Fogelman, Alan M.; Reddy, Srinivasa T.

    2016-01-01

    The site and mechanism of action of the apoA-I mimetic peptide 4F are incompletely understood. Transintestinal cholesterol efflux (TICE) is a process involved in the clearance of excess cholesterol from the body. While TICE is responsible for at least 30% of the clearance of neutral sterols from the circulation into the intestinal lumen, few pharmacological agents have been identified that modulate this pathway. We show first that circulating 4F selectively targets the small intestine (SI) and that it is predominantly transported into the intestinal lumen. This transport of 4F into the SI lumen is transintestinal in nature, and it is modulated by TICE. We also show that circulating 4F increases reverse cholesterol transport from macrophages and cholesterol efflux from lipoproteins via the TICE pathway. We identify the cause of this modulation of TICE either as 4F being a cholesterol acceptor with respect to enterocytes, from which 4F enhances cholesterol efflux, or as 4F being an intestinal chaperone with respect to TICE. Our results assign a novel role for 4F as a modulator of the TICE pathway and suggest that the anti-inflammatory functions of 4F may be a partial consequence of the codependent intestinal transport of both 4F and cholesterol. PMID:27199144

  18. Involvement of Potassium Transport Systems in the Response of Synechocystis PCC 6803 Cyanobacteria to External pH Change, High-Intensity Light Stress and Heavy Metal Stress.

    Science.gov (United States)

    Checchetto, Vanessa; Segalla, Anna; Sato, Yuki; Bergantino, Elisabetta; Szabo, Ildiko; Uozumi, Nobuyuki

    2016-04-01

    The unicellular photosynthetic cyanobacterium, able to survive in varying environments, is the only prokaryote that directly converts solar energy and CO2 into organic material and is thus relevant for primary production in many ecosystems. To maintain the intracellular and intrathylakoid ion homeostasis upon different environmental challenges, the concentration of potassium as a major intracellular cation has to be optimized by various K(+)uptake-mediated transport systems. We reveal here the specific and concerted physiological function of three K(+)transporters of the plasma and thylakoid membranes, namely of SynK (K(+)channel), KtrB (Ktr/Trk/HKT) and KdpA (Kdp) in Synechocystis sp. strain PCC 6803, under specific stress conditions. The behavior of the wild type, single, double and triple mutants was compared, revealing that only Synk contributes to heavy metal-induced stress, while only Ktr/Kdp is involved in osmotic and salt stress adaptation. With regards to pH shifts in the external medium, the Kdp/Ktr uptake systems play an important role in the adaptation to acidic pH. Ktr, by affecting the CO2 concentration mechanism via its action on the bicarbonate transporter SbtA, might also be responsible for the observed effects concerning high-light stress and calcification. In the case of illumination with high-intensity light, a synergistic action of Kdr/Ktp and SynK is required in order to avoid oxidative stress and ensure cell viability. In summary, this study dissects, using growth tests, measurement of photosynthetic activity and analysis of ultrastructure, the physiological role of three K(+)transporters in adaptation of the cyanobacteria to various environmental changes. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Effects of flavonoid mixtures on the transport of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through Caco-2 monolayers: An in vitro and kinetic modeling approach to predict the combined effects on transporter inhibition

    NARCIS (Netherlands)

    Schutte, M.E.; Boersma, M.G.; Verhallen, D.A.M.; Groten, J.P.; Rietjens, I.M.C.M.

    2008-01-01

    This study describes and kinetically models the effect of flavonoid mixtures on PhIP transport through Caco-2 monolayers. Previously it was shown that quercetin, luteolin, naringenin and myricetin increase the apical to basolateral PhIP transport in Caco-2 monolayers. In this study, apigenin was

  20. Ultimate pH values and bacteriological condition of meat and stress metabolites in blood of transported reindeer bulls

    Directory of Open Access Journals (Sweden)

    E. Wiklund

    2001-03-01

    Full Text Available Twenty-three reindeer bulls, aged 2-3 years, fed during two winter months at the Vuolda reindeer research station in Arjeplog, Sweden, were used in the study. The first group of eight reindeer was moved from their feeding corral to a selection corral, captured by lasso and stunned with a captive bolt outside the selection corral. The second group of seven reindeer was moved to the selection corral, captured by lasso and restrained, after which they were loaded onto a lorry- and transported for 1 hour and then slaughtered. The third group of eight reindeer was moved to the selection corral and herded directly onto the lorry, without any manual handling. They were transported for 5 h and then slaughtered. In both transport groups, four reindeer were fitted with pre-programmed automatic blood sampling equipment (ABSE. ABSE sampled blood at predetermined times via a jugular vein catheter. Ultimate pH-values in three muscles (Mm. longissimus, triceps brachii and biceps femoris were significantly lower in the group carefully handled and transported for 5 h compared with the other two groups. The physiological mechanisms behind these results are discussed. Samples from M. semimembranosus were collected at slaughter and after 2, 6 and 10 days of refrigerated storage (+4 °C. The samples were analysed for total counts of aerobic bacteria (pour-plated in Tryptone Glucose Extract Agar, Difco, incubated at 20 °C and 30 °C, respectively for 72 h, coliform bacteria 37 °C (pour-plated in Violet Red Bile Agar, Oxoid, incubated at 37 °C for 24 h, Enterococci (surface-plated onto Slantez and Bartley Agar, Oxoid, incubated at 44 °C for 48 h and Bacillus cereus (surface-plated onto Blood Agar Plates (Blood Agar Base, Difco, supplemented with 5% defibrinated horse blood 30 °C for 24 h. All samples fell in the range 'fit for consumption'. At slaughter, there was no difference in ASAT activity, urea and Cortisol concentrations between the two transported groups

  1. Influence of pH on the Transport of Silver Nanoparticles in Saturated Porous Media: Laboratory Experiments and Modeling

    Science.gov (United States)

    2012-03-01

    the potential toxic effects of AgNPs (USEPA 2010). Recent in vitro and in vivo studies using various cell lines, algae , zooplankton, fish, rats and... TiO2 in Saturated Porous Media: Effects of pH, Surfactants and Flow Velocity.” Water Research, 45(2), 839-851. He, F., Zhang, M., Qian, T., and Zhao...of silver nanoparticles (AgNPs), the largest and fastest growing category of nanomaterials, and their potential for toxic effects to both humans

  2. A minimization procedure for estimating the power deposition and heat transport from the temperature response to auxiliary power modulation

    International Nuclear Information System (INIS)

    Eester, Dirk van

    2004-01-01

    A method commonly used for determining where externally launched power is absorbed inside a tokamak plasma is to examine the temperature response to modulation of the launched power. Strictly speaking, this response merely provides a first good guess of the actual power deposition rather than the deposition profile itself: not only local heat sources but also heat losses and heat wave propagation affect the temperature response at a given position. Making use of this, at first sight non-desirable, effect modulation becomes a useful tool for conducting transport studies. In this paper a minimization method based on a simple conduction-convection model is proposed for deducing the power deposition and transport characteristics from the experimentally measured (electron) energy density response to a modulation of the auxiliary heating power. An L-mode JET example illustrates the potential of the technique

  3. Influence of pH on the Transport of Silver Nanoparticles in Saturated Porous Media: Laboratory Experiments and Modeling

    Science.gov (United States)

    Given the ubiquity of silver nanoparticles (AgNPs), the largest and fastest growing category of nanomaterials, and their potential for toxic effects to both humans and the environment, it is important to understand their environmental fate and transport. The purpose of this stud...

  4. Effect of rotational speed modulation on heat transport in a fluid layer with temperature dependent viscosity and internal heat source

    Directory of Open Access Journals (Sweden)

    B.S. Bhadauria

    2014-12-01

    Full Text Available In this paper, a theoretical investigation has been carried out to study the combined effect of rotation speed modulation and internal heating on thermal instability in a temperature dependent viscous horizontal fluid layer. Rayleigh–Bénard momentum equation with Coriolis term has been considered to describe the convective flow. The system is rotating about it is own axis with non-uniform rotational speed. In particular, a time-periodic and sinusoidally varying rotational speed has been considered. A weak nonlinear stability analysis is performed to find the effect of modulation on heat transport. Nusselt number is obtained in terms of amplitude of convection and internal Rayleigh number, and depicted graphically for showing the effects of various parameters of the system. The effect of modulated rotation speed is found to have a stabilizing effect for different values of modulation frequency. Further, internal heating and thermo-rheological parameters are found to destabilize the system.

  5. Hydrogen sulfide: role in ion channel and transporter modulation in the eye

    Directory of Open Access Journals (Sweden)

    Ya Fatou eNjie-Mbye

    2012-07-01

    Full Text Available Hydrogen sulfide (H2S, a colorless gas with a characteristic smell of rotten eggs, has been portrayed for decades as a toxic environmental pollutant. Since evidence of its basal production in mammalian tissues a decade ago, H2S has attracted substantial interest as a potential inorganic gaseous mediator with biological importance in cellular functions. Current research suggests that, next to its counterparts nitric oxide and carbon monoxide, H2S is an important multifunctional signaling molecule with pivotal regulatory roles in various physiological and pathophysiological processes as diverse as learning and memory, modulation of synaptic activities, cell survival, inflammation and maintenance of vascular tone in the central nervous and cardiovascular systems. In contrast, there are few reports of a regulatory role of H2S in the eye. Accumulating reports on the pharmacological role of H2S in ocular tissues indicate the existence of a functional trans-sulfuration pathway and a potential physiological role for H2S as a gaseous neuromodulator in the eye. Thus, understanding the role of H2S in vision-related processes is imperative to our expanding knowledge of this molecule as a gaseous mediator in ocular tissues. This review aims to provide a comprehensive and current understanding of the potential role of H2S as a signaling molecule in the eye. This objective is achieved by discussing the involvement of H2S in the regulation of (1 ion channels such as calcium (L-type, T-type and intracellular stores, potassium (KATP and small conductance channels and chloride channels, (2 glutamate transporters such as EAAT1/GLAST and the L-cystine/glutamate antiporter. The role of H2S as an important mediator in cellular functions and physiological processes that are triggered by its interaction with ion channels/transporters in the eye will also be discussed.

  6. Induction of salt tolerance in Azolla microphylla Kaulf through modulation of antioxidant enzymes and ion transport.

    Science.gov (United States)

    Abraham, Gerard; Dhar, Dolly Wattal

    2010-09-01

    Azolla microphylla plants exposed directly to NaCl (13 dsm(-1)) did not survive the salinity treatment beyond a period of one day, whereas plants exposed directly to 4 and 9 dsm(-1) NaCl were able to grow and produce biomass. However, plants pre-exposed to NaCl (2 dsm(-1)) for 7 days on subsequent exposure to 13 dsm(-1) NaCl were able to grow and produce biomass although at a slow rate and are hereinafter designated as pre-exposed plants. The pre-exposed and directly exposed plants distinctly differed in their response to salt in terms of lipid peroxidation, proline accumulation, activity of antioxidant enzymes, such as SOD, APX, and CAT, and Na(+)/K(+) ratio. Efficient modulation of antioxidant enzymes coupled with regulation of ion transport play an important role in the induction of salt tolerance. Results show that it is possible to induce salt adaptation in A. microphylla by pre-exposing them to low concentrations of NaCl.

  7. Laboratory investigations into the reactive transport module of carbon dioxide sequestration and geochemical simulation

    Energy Technology Data Exchange (ETDEWEB)

    Heidaryan, E. [Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Masjidosolayman Branch; Enayati, M.; Mokhtari, B. [Iranian Offshore Oil Co., Tehran (Iran, Islamic Republic of)

    2008-07-01

    Over long time periods, geological sequestration in some systems shows mineralization effects or mineral sequestration of carbon dioxide, converting the carbon dioxide to a less mobile form. However, a detailed investigation of these geological systems is needed before disposing of carbon dioxide into these formations. Depleted oil and gas reservoirs and underground aquifers are proposed candidates for carbon dioxide injection. This paper presented an experimental investigation into the reactive transport module for handling aquifer sequestration of carbon dioxide and modeling of simultaneous geochemical reactions. Two cases of laboratory carbon dioxide sequestration experiments, conducted for different rock systems were modeled using the fully coupled geochemical compositional simulator. The relevant permeability relationships were compared to determine the best fit with the experimental results. The paper discussed the theory of modeling; geochemical reactions and mineral trapping of carbon dioxide; and application simulator for modeling including the remodeling of flow experiments. It was concluded that simulated changes in porosity and permeability could mimic experimental results to some extent. The study satisfactorily simulated the results of experimental observations and permeability results could be improved if the Kozeny-Carman equation was replaced by the Civan power law. 6 refs., 2 tabs., 21 figs.

  8. Transportation life cycle assessment (LCA) synthesis : life cycle assessment learning module series.

    Science.gov (United States)

    2015-03-12

    The Life Cycle Assessment Learning Module Series is a set of narrated, self-advancing slideshows on : various topics related to environmental life cycle assessment (LCA). This research project produced the first 27 of such modules, which : are freely...

  9. Evaluation of four-dimensional nonbinary LDPC-coded modulation for next-generation long-haul optical transport networks.

    Science.gov (United States)

    Zhang, Yequn; Arabaci, Murat; Djordjevic, Ivan B

    2012-04-09

    Leveraging the advanced coherent optical communication technologies, this paper explores the feasibility of using four-dimensional (4D) nonbinary LDPC-coded modulation (4D-NB-LDPC-CM) schemes for long-haul transmission in future optical transport networks. In contrast to our previous works on 4D-NB-LDPC-CM which considered amplified spontaneous emission (ASE) noise as the dominant impairment, this paper undertakes transmission in a more realistic optical fiber transmission environment, taking into account impairments due to dispersion effects, nonlinear phase noise, Kerr nonlinearities, and stimulated Raman scattering in addition to ASE noise. We first reveal the advantages of using 4D modulation formats in LDPC-coded modulation instead of conventional two-dimensional (2D) modulation formats used with polarization-division multiplexing (PDM). Then we demonstrate that 4D LDPC-coded modulation schemes with nonbinary LDPC component codes significantly outperform not only their conventional PDM-2D counterparts but also the corresponding 4D bit-interleaved LDPC-coded modulation (4D-BI-LDPC-CM) schemes, which employ binary LDPC codes as component codes. We also show that the transmission reach improvement offered by the 4D-NB-LDPC-CM over 4D-BI-LDPC-CM increases as the underlying constellation size and hence the spectral efficiency of transmission increases. Our results suggest that 4D-NB-LDPC-CM can be an excellent candidate for long-haul transmission in next-generation optical networks.

  10. Opto-electro-modulated transient photovoltage and photocurrent system for investigation of charge transport and recombination in solar cells.

    Science.gov (United States)

    Shi, Jiangjian; Li, Dongmei; Luo, Yanhong; Wu, Huijue; Meng, Qingbo

    2016-12-01

    An opto-electro-modulated transient photovoltage/photocurrent system has been developed to probe microscopic charge processes of a solar cell in its adjustable operating conditions. The reliability of this system is carefully determined by electric circuit simulations and experimental measurements. Using this system, the charge transport, recombination and storage properties of a conventional multicrystalline silicon solar cell under different steady-state bias voltages, and light illumination intensities are investigated. This system has also been applied to study the influence of the hole transport material layer on charge extraction and the microscopic charge processes behind the widely considered photoelectric hysteresis in perovskite solar cells.

  11. Low-Temperature Band Transport and Impact of Contact Resistance in Organic Field-Effect Transistors Based on Single-Crystal Films of Ph-BTBT-C10

    Science.gov (United States)

    Cho, Joung-min; Mori, Takehiko

    2016-06-01

    Transistors based on single-crystal films of 2-decyl-7-phenyl-[1]benzothieno[3,2-b][1]benzothiophene (Ph-BTBT-10) fabricated using the blade-coating method are investigated by the four-probe method down to low temperatures. The four-probe mobility is as large as 18 cm2/V s at room temperature, and increases to 45 cm2/V s at 80 K. At 60 K the two-probe mobility drops abruptly by about 50%, but the mobility drop is mostly attributed to the increase of the source resistance. The carrier transport in the present single-crystal film is regarded as essentially bandlike down to 30 K.

  12. New evidence and impact of electron transport non-linearities based on new perturbative inter-modulation analysis

    Science.gov (United States)

    van Berkel, M.; Kobayashi, T.; Igami, H.; Vandersteen, G.; Hogeweij, G. M. D.; Tanaka, K.; Tamura, N.; Zwart, H. J.; Kubo, S.; Ito, S.; Tsuchiya, H.; de Baar, M. R.; LHD Experiment Group

    2017-12-01

    A new methodology to analyze non-linear components in perturbative transport experiments is introduced. The methodology has been experimentally validated in the Large Helical Device for the electron heat transport channel. Electron cyclotron resonance heating with different modulation frequencies by two gyrotrons has been used to directly quantify the amplitude of the non-linear component at the inter-modulation frequencies. The measurements show significant quadratic non-linear contributions and also the absence of cubic and higher order components. The non-linear component is analyzed using the Volterra series, which is the non-linear generalization of transfer functions. This allows us to study the radial distribution of the non-linearity of the plasma and to reconstruct linear profiles where the measurements were not distorted by non-linearities. The reconstructed linear profiles are significantly different from the measured profiles, demonstrating the significant impact that non-linearity can have.

  13. Enigma interacts with adaptor protein with PH and SH2 domains to control insulin-induced actin cytoskeleton remodeling and glucose transporter 4 translocation.

    Science.gov (United States)

    Barrès, Romain; Grémeaux, Thierry; Gual, Philippe; Gonzalez, Teresa; Gugenheim, Jean; Tran, Albert; Le Marchand-Brustel, Yannick; Tanti, Jean-François

    2006-11-01

    APS (adaptor protein with PH and SH2 domains) initiates a phosphatidylinositol 3-kinase-independent pathway involved in insulin-stimulated glucose transport. We recently identified Enigma, a PDZ and LIM domain-containing protein, as a partner of APS and showed that APS-Enigma complex plays a critical role in actin cytoskeleton organization in fibroblastic cells. Because actin rearrangement is important for insulin-induced glucose transporter 4 (Glut 4) translocation, we studied the potential involvement of Enigma in insulin-induced glucose transport in 3T3-L1 adipocytes. Enigma mRNA was expressed in differentiated adipocytes and APS and Enigma were colocalized with cortical actin. Expression of an APS mutant unable to bind Enigma increased the insulin-induced Glut 4 translocation to the plasma membrane. By contrast, overexpression of Enigma inhibited insulin-stimulated glucose transport and Glut 4 translocation without alterations in proximal insulin signaling. This inhibitory effect was prevented with the deletion of the LIM domains of Enigma. Using time-lapse fluorescent microscopy of green fluorescent protein-actin, we demonstrated that the overexpression of Enigma altered insulin-induced actin rearrangements, whereas the expression of Enigma without its LIM domains was without effect. A physiological link between increased expression of Enigma and an alteration in insulin-induced glucose uptake was suggested by the increase in Enigma mRNA expression in adipose tissue of diabetic obese patients. Taken together, these data strongly suggest that the interaction between APS and Enigma is involved in insulin-induced Glut 4 translocation by regulating cortical actin remodeling and raise the possibility that modification of APS/Enigma ratio could participate in the alteration of insulin-induced glucose uptake in adipose tissue.

  14. Pitavastatin Differentially Modulates MicroRNA-Associated Cholesterol Transport Proteins in Macrophages.

    Directory of Open Access Journals (Sweden)

    Haijun Zhang

    Full Text Available There is emerging evidence identifying microRNAs (miRNAs as mediators of statin-induced cholesterol efflux, notably through the ATP-binding cassette transporter A1 (ABCA1 in macrophages. The objective of this study was to assess the impact of an HMG-CoA reductase inhibitor, pitavastatin, on macrophage miRNAs in the presence and absence of oxidized-LDL, a hallmark of a pro-atherogenic milieu. Treatment of human THP-1 cells with pitavastatin prevented the oxLDL-mediated suppression of miR-33a, -33b and -758 mRNA in these cells, an effect which was not uniquely attributable to induction of SREBP2. Induction of ABCA1 mRNA and protein by oxLDL was inhibited (30% by pitavastatin, while oxLDL or pitavastatin alone significantly induced and repressed ABCA1 expression, respectively. These findings are consistent with previous reports in macrophages. miRNA profiling was also performed using a miRNA array. We identified specific miRNAs which were up-regulated (122 and down-regulated (107 in THP-1 cells treated with oxLDL plus pitavastatin versus oxLDL alone, indicating distinct regulatory networks in these cells. Moreover, several of the differentially expressed miRNAs identified are functionally associated with cholesterol trafficking (six miRNAs in cells treated with oxLDL versus oxLDL plus pitavastatin. Our findings indicate that pitavastatin can differentially modulate miRNA in the presence of oxLDL; and, our results provide evidence that the net effect on cholesterol homeostasis is mediated by a network of miRNAs.

  15. A 'V' shaped superconducting levitation module for lift and guidance of a magnetic transportation system

    Energy Technology Data Exchange (ETDEWEB)

    D' Ovidio, G. [Transportation Area - DAU, University of L' Aquila, Poggio di Roio, 67040 L' Aquila (Italy)], E-mail: dovidio@dau.ing.univaq.it; Crisi, F.; Lanzara, G. [Transportation Area - DAU, University of L' Aquila, Poggio di Roio, 67040 L' Aquila (Italy)

    2008-07-15

    A novel, YBCO based, magnetic transportation system (MagTranS) is presented and described. The feasibility of this system has been successfully tested and confirmed in a laboratory using a scaled demonstrator system. The MagTranS levitation system uses a stable, self-balancing 'V' shaped superconducting module for both lift and guidance of vehicles. The work concept of the MagTranS levitation module is described and differences with regards to the maglev current systems are highlighted. The results of levitation tests performed using a measurement set-up are presented and discussed. Lastly, levitation module performance studies are also carried out using numerical finite element analysis.

  16. Modulation and Functional Role of the Orientations of the N- and P-Domains of Cu+ -Transporting ATPase along the Ion Transport Cycle.

    Science.gov (United States)

    Meng, Dan; Bruschweiler-Li, Lei; Zhang, Fengli; Brüschweiler, Rafael

    2015-08-18

    Ion transport of different P-type ATPases is regulated similarly through the interplay of multiple protein domains. In the presence of ATP, binding of a cation to the ion binding site in the transmembrane helices leads to the phosphorylation of the P-domain, allowing ion transfer across the membrane. The details of the mechanism, however, are not clear. Here, we report the modulation of the orientation between the N- and P-domains of Cu(+)-transporting ATPase along the ion transport cycle using high-resolution nuclear magnetic resonance spectroscopy in solution. On the basis of residual dipolar coupling measurements, it is found that the interdomain orientation (relative openness) of the N- and P-domains is distinctly modulated depending on the specific state of the N- and P-domains along the ion translocation cycle. The two domains' relative position in the apo state is semiopen, whereas it becomes closed upon binding of ATP to the N-domain. After phosphorylation of the P-domain and the release of ADP, the opening, however, becomes the widest among all the states. We reason such wide opening resulting from the departure of ADP prepares the N- and P-domains to accommodate the A-domain for interaction and, hence, promote ion transport and allow dephosphorylation of the P-domain. Such wide interdomain opening is abolished when an Asn to Asp mutation is introduced into the conserved DXXK motif located in the hinge region of the N- and P-domains of Cu(+)-ATPase, suggesting the indispensible role of the N- and P-interdomain orientation during ion transportation. Our results shed new light on the structural and mechanistic details of P-type ATPase function at large.

  17. Experimental studies and modelling of cation interactions with solid materials: application to the MIMICC project. (Multidimensional Instrumented Module for Investigations on chemistry-transport Coupled Codes)

    International Nuclear Information System (INIS)

    Hardin, Emmanuelle

    1999-01-01

    The study of cation interactions with solid materials is useful in order to define the chemistry interaction component of the MIMICC project (Multidimensional Instrumented Module for Investigations on chemistry-transport Coupled Codes). This project will validate the chemistry-transport coupled codes. Database have to be supplied on the cesium or ytterbium interactions with solid materials in suspension. The solid materials are: a strong cation exchange resin, a natural sand which presents small impurities, and a zirconium phosphate. The cation exchange resin is useful to check that the surface complexation theory can be applied on a pure cation exchanger. The sand is a natural material, and its isotherms will be interpreted using pure oxide-cation system data, such as pure silica-cation data. Then the study on the zirconium phosphate salt is interesting because of the increasing complexity in the processes (dissolution, sorption and co-precipitation). These data will enable to approach natural systems, constituted by several complex solids which can interfere on each other. These data can also be used for chemistry-transport coupled codes. Potentiometric titration, sorption isotherms, sorption kinetics, cation surface saturation curves are made, in order to obtain the different parameters relevant to the cation sorption at the solid surface, for each solid-electrolyte-cation system. The influence of different parameters such as ionic strength, pH, and electrolyte is estimated. All the experimental curves are fitted with FITEQL code based on the surface complexation theory using the constant capacitance model, in order to give a mechanistic interpretation of the ion retention phenomenon at the solid surface. The speciation curves of all systems are plotted, using the FITEQL code too. Systems with an increasing complexity are studied: dissolution, sorption and coprecipitation coexist in the cation-salt systems. Then the data obtained on each single solid, considered

  18. All Internal Segmental Bone Transport and Optional Lengthening With a Newly Developed Universal Cylinder-Kombi-Tube Module for Motorized Nails-Description of a Surgical Technique.

    Science.gov (United States)

    Krettek, Christian; El Naga, Ashraf

    2017-10-01

    Segmental transport is an effective method of treatment for segmental defects, but the need for external fixation during the transport phase is a disadvantage. To avoid external fixation, we have developed a Cylinder-Kombi-Tube Segmental Transport (CKTST) module for combination with a commercially available motorized lengthening nail. This CKTST module allows for an all-internal segmental bone transport and also allows for optional lengthening if needed. The concept and surgical technique of CKTST are described and illustrated with a clinical case.

  19. Serotonin transporter genotype modulates subgenual response to fearful faces using an incidental task.

    Science.gov (United States)

    O'Nions, Elizabeth J P; Dolan, Raymond J; Roiser, Jonathan P

    2011-11-01

    This study assessed the impact of serotonin transporter genotype (5-HTTLPR) on regional responses to emotional faces in the amygdala and subgenual cingulate cortex (sgACC), while subjects performed a gender discrimination task. Although we found no evidence for greater amygdala reactivity or reduced amygdala-sgACC coupling in short variant 5-HTTLPR homozygotes (s/s), we observed an interaction between genotype and emotion in sgACC. Only long variant homozygotes (la/la) exhibited subgenual deactivation to fearful versus neutral faces, whereas the effect in s/s subjects was in the other direction. This absence of subgenual deactivation in s/s subjects parallels a recent finding in depressed subjects [Grimm, S., Boesiger, P., Beck, J., Schuepbach, D., Bermpohl, F., Walter, M., et al. Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology, 34, 932-943, 2009]. Taken together, the findings suggest that subgenual cingulate activity may play an important role in regulating the impact of aversive stimuli, potentially conferring greater resilience to the effects of aversive stimuli in la/la subjects. Using dynamic causal modeling of functional magnetic resonance imaging data, we explored the effects of genotype on effective connectivity and emotion-specific changes in coupling across a network of regions implicated in social processing. Viewing fearful faces enhanced bidirectional excitatory coupling between the amygdala and the fusiform gyrus, and increased the inhibitory influence of the amygdala over the sgACC, although this modulation of coupling did not differ between the genotype groups. The findings are discussed in relation to the role of sgACC and serotonin in moderating responses to aversive stimuli [Dayan, P., & Huys, Q. J., Serotonin, inhibition, and negative mood. PLoS Comput Biol, 4, e4, 2008; Mayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K., Jerabek, P. A., et

  20. Atmospheric radionuclide transport model with radon postprocessor and SBG module. Model description version 2.8.0; ARTM. Atmosphaerisches Radionuklid-Transport-Modell mit Radon Postprozessor und SBG-Modul. Modellbeschreibung zu Version 2.8.0

    Energy Technology Data Exchange (ETDEWEB)

    Richter, Cornelia; Sogalla, Martin; Thielen, Harald; Martens, Reinhard

    2015-04-20

    The study on the atmospheric radionuclide transport model with radon postprocessor and SBG module (model description version 2.8.0) covers the following issues: determination of emissions, radioactive decay, atmospheric dispersion calculation for radioactive gases, atmospheric dispersion calculation for radioactive dusts, determination of the gamma cloud radiation (gamma submersion), terrain roughness, effective source height, calculation area and model points, geographic reference systems and coordinate transformations, meteorological data, use of invalid meteorological data sets, consideration of statistical uncertainties, consideration of housings, consideration of bumpiness, consideration of terrain roughness, use of frequency distributions of the hourly dispersion situation, consideration of the vegetation period (summer), the radon post processor radon.exe, the SBG module, modeling of wind fields, shading settings.

  1. Control of red cell volume and pH in trout: Effects of isoproterenol, transport inhibitors, and extracellular pH in bicarbonate/carbon dioxide-buffered media

    DEFF Research Database (Denmark)

    NIKINMAA, M; STEFFENSEN, JF; TUFTS, BL

    1987-01-01

    The effects of extracellular pH and beta-adrenergic stimula-tion on the volume and pH of rainbow. trout red cells were studied in HCO3-/ CO2 butfered media. A decrease in extracellular pH caused an increase in red cell volume and a decrease in intracellular pH. The pH-induced changes in cell volume......, and that the Na+/H+ exchanger is not activated by changes in intracellular pH alone. The adrenergic drug, isoproterenol, promoted cell swelling and proton extrusion even in the presence of 10 mM HCO3-, showing that the adrenergic response plays a significant role in the control of cytoplasmic pH. These responses...... were enhanced by a decrease in extracellular pH, showing that the adrenergic response is of benefit to stressed animals. DIDS markedly enhanced the effect of isoproterenol on the pHi, but abolished the increase in red cell volume. The effects of furosemide were similar to those of DIDS, suggesting...

  2. Development of efficiency module of organization of Arctic sea cargo transportation with application of neural network technologies

    Science.gov (United States)

    Sobolevskaya, E. Yu; Glushkov, S. V.; Levchenko, N. G.; Orlov, A. P.

    2018-05-01

    The analysis of software intended for organizing and managing the processes of sea cargo transportation has been carried out. The shortcomings of information resources are presented, for the organization of work in the Arctic and Subarctic regions of the Far East: the lack of decision support systems, the lack of factor analysis to calculate the time and cost of delivery. The architecture of the module for calculating the effectiveness of the organization of sea cargo transportation has been developed. The simulation process has been considered, which is based on the neural network. The main classification factors with their weighting coefficients have been identified. The architecture of the neural network has been developed to calculate the efficiency of the organization of sea cargo transportation in Arctic conditions. The architecture of the intellectual system of organization of sea cargo transportation has been developed, taking into account the difficult navigation conditions in the Arctic. Its implementation will allow one to provide the management of the shipping company with predictive analytics; to support decision-making; to calculate the most efficient delivery route; to provide on demand online transportation forecast, to minimize the shipping cost, delays in transit, and risks to cargo safety.

  3. PH sensor

    OpenAIRE

    Artero, C.; Nogueras Cervera, Marc; Manuel Lázaro, Antonio

    2012-01-01

    This paper presents a design of a marine instrument for the measurement of pH in seawater. The measurement system consists of a pH electrode connected to the underwater observatory OBSEA. The extracted data are useful for scientists researching ocean acidification. Peer Reviewed

  4. EOS9nT: A TOUGH2 module for the simulation of flow and solute/colloid transport

    International Nuclear Information System (INIS)

    Moridis, G.J.; Wu, Y.S.; Pruess, K.

    1998-04-01

    EOS9nT is a new TOUGH2 module for the simulation of flow and transport of an arbitrary number n of tracers (solutes and/or colloids) in the subsurface. The module first solves the flow-related equations, which are comprised of (a) the Richards equation and, depending on conditions, may also include (b) the flow equation of a dense brine or aqueous suspension and/or (c) the heat equation. A second set of transport equations, corresponding to the n tracers, are then solved sequentially. The low concentrations of the n tracers are considered to have no effect on the liquid phase, thus making possible the decoupling of their equations. The first set of equations in EOS9nT provides the flow regime and account for fluid density variations due to thermal and/or solute concentration effects. The n tracer transport equations account for sorption, radioactive decay, advection, hydrodynamic dispersion, molecular diffusion, as well as filtration (for colloids only). EOS9nT can handle gridblocks or irregular geometry in three-dimensional domains. Preliminary results from four 1-D verification problems show an excellent agreement between the numerical predictions and the known analytical solutions

  5. Spermine modulates the expression of two probable polyamine transporter genes and determines growth responses to cadaverine in Arabidopsis.

    Science.gov (United States)

    Sagor, G H M; Berberich, Thomas; Kojima, Seiji; Niitsu, Masaru; Kusano, Tomonobu

    2016-06-01

    Two genes, LAT1 and OCT1 , are likely to be involved in polyamine transport in Arabidopsis. Endogenous spermine levels modulate their expression and determine the sensitivity to cadaverine. Arabidopsis spermine (Spm) synthase (SPMS) gene-deficient mutant was previously shown to be rather resistant to the diamine cadaverine (Cad). Furthermore, a mutant deficient in polyamine oxidase 4 gene, accumulating about twofold more of Spm than wild type plants, showed increased sensitivity to Cad. It suggests that endogenous Spm content determines growth responses to Cad in Arabidopsis thaliana. Here, we showed that Arabidopsis seedlings pretreated with Spm absorbs more Cad and has shorter root growth, and that the transgenic Arabidopsis plants overexpressing the SPMS gene are hypersensitive to Cad, further supporting the above idea. The transgenic Arabidopsis overexpressing L-Amino acid Transporter 1 (LAT1) absorbed more Cad and showed increased Cad sensitivity, suggesting that LAT1 functions as a Cad importer. Recently, other research group reported that Organic Cation Transporter 1 (OCT1) is a causal gene which determines the Cad sensitivity of various Arabidopsis accessions. Furthermore, their results suggested that OCT1 is involved in Cad efflux. Thus we monitored the expression of OCT1 and LAT1 during the above experiments. Based on the results, we proposed a model in which the level of Spm content modulates the expression of OCT1 and LAT1, and determines Cad sensitivity of Arabidopsis.

  6. Density Modulation Experiments to Determine Particle Transport Coefficients on HT-7 Tokamak

    International Nuclear Information System (INIS)

    Jie Yinxian; Gao Xiang; Tanaka, K; Sakamoto, R; Toi, K; Liu Haiqing; Gao Li; Asif, M; Liu Jin; Xu Qiang; Tong Xingde; Cheng Yongfei

    2006-01-01

    The particle diffusion coefficient and the convection velocity were studied based on the density modulation using D 2 gas puffing on the HT-7 tokamak. The density was measured by a five-channel FIR interferometer. The density modulation amplitude was 10% of the central chord averaged background density and the modulation frequency was 10 Hz in the experiments. The particle diffusion coefficient (D) and the convection velocity (V) were obtained for different background plasmas with the central chord averaged density e > = 1.5x10 19 m -3 and 3.0x10 19 m -3 respectively. It was observed that the influence of density modulation on the main plasma parameters was very weak. This technology is expected to be useful for the analysis of LHW and IBW heated plasmas on HT-7 tokamak in the near future

  7. Modulators of membrane drug transporters potentiate the activity of the DMI fungicide oxpoconazole against Botrytis cinerea

    NARCIS (Netherlands)

    Hayashi, K.; Schoonbeek, H.; Waard, de M.A.

    2003-01-01

    Modulators known to reduce multidrug resistance in tumour cells were tested for their potency to synergize the fungitoxic activity of the fungicide oxpoconazole, a sterol demethylation inhibitor (DMI), against Botrytis cinerea Pers. Chlorpromazine, a phenothiazine compound known as a calmodulin

  8. Modeling pH variation in reverse osmosis.

    Science.gov (United States)

    Nir, Oded; Bishop, Noga Fridman; Lahav, Ori; Freger, Viatcheslav

    2015-12-15

    The transport of hydronium and hydroxide ions through reverse osmosis membranes constitutes a unique case of ionic species characterized by uncommonly high permeabilities. Combined with electromigration, this leads to complex behavior of permeate pH, e.g., negative rejection, as often observed for monovalent ions in nanofiltration of salt mixtures. In this work we employed a rigorous phenomenological approach combined with chemical equilibrium to describe the trans-membrane transport of hydronium and hydroxide ions along with salt transport and calculate the resulting permeate pH. Starting from the Nernst-Planck equation, a full non-linear transport equation was derived, for which an approximate solution was proposed based on the analytical solution previously developed for trace ions in a dominant salt. Using the developed approximate equation, transport coefficients were deduced from experimental results obtained using a spiral wound reverse osmosis module operated under varying permeate flux (2-11 μm/s), NaCl feed concentrations (0.04-0.18 M) and feed pH values (5.5-9.0). The approximate equation agreed well with the experimental results, corroborating the finding that diffusion and electromigration, rather than a priori neglected convection, were the major contributors to the transport of hydronium and hydroxide. The approach presented here has the potential to improve the predictive capacity of reverse osmosis transport models for acid-base species, thereby improving process design/control. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Perturbative studies of toroidal momentum transport using neutral beam injection modulation in the Joint European Torus: Experimental results, analysis methodology, and first principles modeling

    DEFF Research Database (Denmark)

    Mantica, P.; Tala, T.; Ferreira, J.S.

    2010-01-01

    Perturbative experiments have been carried out in the Joint European Torus [Fusion Sci. Technol. 53(4) (2008)] in order to identify the diffusive and convective components of toroidal momentum transport. The torque source was modulated either by modulating tangential neutral beam power...... or by modulating in antiphase tangential and normal beams to produce a torque perturbation in the absence of a power perturbation. The resulting periodic perturbation in the toroidal rotation velocity was modeled using time-dependent transport simulations in order to extract empirical profiles of momentum...

  10. Field control of anisotropic spin transport and spin helix dynamics in a modulation-doped GaAs quantum well

    Science.gov (United States)

    Anghel, S.; Passmann, F.; Singh, A.; Ruppert, C.; Poshakinskiy, A. V.; Tarasenko, S. A.; Moore, J. N.; Yusa, G.; Mano, T.; Noda, T.; Li, X.; Bristow, A. D.; Betz, M.

    2018-03-01

    Electron spin transport and dynamics are investigated in a single, high-mobility, modulation-doped, GaAs quantum well using ultrafast two-color Kerr-rotation microspectroscopy, supported by qualitative kinetic theory simulations of spin diffusion and transport. Evolution of the spins is governed by the Dresselhaus bulk and Rashba structural inversion asymmetries, which manifest as an effective magnetic field that can be extracted directly from the experimental coherent spin precession. A spin-precession length λSOI is defined as one complete precession in the effective magnetic field. It is observed that application of (i) an out-of-plane electric field changes the spin decay time and λSOI through the Rashba component of the spin-orbit coupling, (ii) an in-plane magnetic field allows for extraction of the Dresselhaus and Rashba parameters, and (iii) an in-plane electric field markedly modifies both the λSOI and diffusion coefficient.

  11. α2-Adrenergic modulation of the glutamate receptor and transporter function in a chronic ocular hypertension model.

    Science.gov (United States)

    Jung, Kyoung In; Kim, Jie Hyun; Park, Chan Kee

    2015-10-15

    Excitotoxicity, glutamate-induced toxic effects to retinal ganglion cells (RGCs), is one of several mechanisms of RGC loss suggested in glaucoma. In this study, we focused on the role of glutamate transporter of glial cells as well as N-methyl-d-aspartate (NMDA) receptor with regard to glutamate toxicity in glaucoma. We also investigated whether α2-adrenoceptor activation could modulate glutamate transporters and NMDA receptors in a chronic ocular hypertension model. Brimonidine 0.15% was administered topically to the eyes of experimental glaucoma and control animals twice daily. After 8 weeks of intraocular pressure (IOP) elevation, staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) revealed an increase in the ganglion cell layer, and the number of TUNEL-positive cells was reduced by brimonidine treatment (P<0.05). Animals with experimentally induced glaucoma exhibited an increase in retinal stress marker glial fibrillary acidic protein (GFAP) immunoreactivity; brimonidine treatment reduced GFAP. Excitatory amino acid transporter 1(EAAT1) expression remained stable throughout the period of chronic ocular hypertension. α2-Adrenergic treatment upregulated EAAT1 protein levels (P<0.05). NMDA receptor (GluN1) expression was stimulated by chronic elevation of IOP, and GluN1-positive cells in ganglion cell layer were co-localized with TUNEL staining. Brimonidine administration suppressed GluN1 levels (P<0.05). These results indicate that brimonidine decreased RGC apoptosis, upregulating EAAT1 and downregulating NMDA receptors. We suggest that topical brimonidine treatment may decrease the glutamate excitotoxicity through modulation of glutamate transporter and NMDA receptor in glaucoma. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Magnetoquantum transport in a modulated 2D electron gas with spin-orbit interaction

    International Nuclear Information System (INIS)

    Gumbs, Godfrey; Huang, Danhong

    2009-01-01

    We investigate the effects of spin-orbit interaction (SOI) and plane-perpendicular magnetic field on the conductivity of a two-dimensional electron system in the presence of one-dimensional electrostatic modulation. The calculations are performed when a low-intensity, low-frequency external electric field is applied. The Kubo formula for the conductivity is employed in the calculation. The single-particle eigenstates which depend on the strengths of the magnetic field, the SOI and modulation potential, are calculated and then used to determine the conductivity. We present numerical results for the conductivity along the channels as well as the tunneling conductivity perpendicular to the constrictions as functions of the modulation potential, the SOI and the magnetic field. We demonstrate that the effect of finite frequency is to related to the reduction of both the longitudinal and transverse conductivities.

  13. Complex quantum transport in a modulation doped strained Ge quantum well heterostructure with a high mobility 2D hole gas

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, C., E-mail: c.morrison.2@warwick.ac.uk; Casteleiro, C.; Leadley, D. R.; Myronov, M. [Department of Physics, University of Warwick, Coventry CV4 7AL (United Kingdom)

    2016-09-05

    The complex quantum transport of a strained Ge quantum well (QW) modulation doped heterostructure with two types of mobile carriers has been observed. The two dimensional hole gas (2DHG) in the Ge QW exhibits an exceptionally high mobility of 780 000 cm{sup 2}/Vs at temperatures below 10 K. Through analysis of Shubnikov de-Haas oscillations in the magnetoresistance of this 2DHG below 2 K, the hole effective mass is found to be 0.065 m{sub 0}. Anomalous conductance peaks are observed at higher fields which deviate from standard Shubnikov de-Haas and quantum Hall effect behaviour due to conduction via multiple carrier types. Despite this complex behaviour, analysis using a transport model with two conductive channels explains this behaviour and allows key physical parameters such as the carrier effective mass, transport, and quantum lifetimes and conductivity of the electrically active layers to be extracted. This finding is important for electronic device applications, since inclusion of highly doped interlayers which are electrically active, for enhancement of, for example, room temperature carrier mobility, does not prevent analysis of quantum transport in a QW.

  14. Complex quantum transport in a modulation doped strained Ge quantum well heterostructure with a high mobility 2D hole gas

    Science.gov (United States)

    Morrison, C.; Casteleiro, C.; Leadley, D. R.; Myronov, M.

    2016-09-01

    The complex quantum transport of a strained Ge quantum well (QW) modulation doped heterostructure with two types of mobile carriers has been observed. The two dimensional hole gas (2DHG) in the Ge QW exhibits an exceptionally high mobility of 780 000 cm2/Vs at temperatures below 10 K. Through analysis of Shubnikov de-Haas oscillations in the magnetoresistance of this 2DHG below 2 K, the hole effective mass is found to be 0.065 m0. Anomalous conductance peaks are observed at higher fields which deviate from standard Shubnikov de-Haas and quantum Hall effect behaviour due to conduction via multiple carrier types. Despite this complex behaviour, analysis using a transport model with two conductive channels explains this behaviour and allows key physical parameters such as the carrier effective mass, transport, and quantum lifetimes and conductivity of the electrically active layers to be extracted. This finding is important for electronic device applications, since inclusion of highly doped interlayers which are electrically active, for enhancement of, for example, room temperature carrier mobility, does not prevent analysis of quantum transport in a QW.

  15. N-MYC down-regulated-like proteins regulate meristem initiation by modulating auxin transport and MAX2 expression.

    Science.gov (United States)

    Mudgil, Yashwanti; Ghawana, Sanjay; Jones, Alan M

    2013-01-01

    N-MYC down-regulated-like (NDL) proteins interact with the Gβ subunit (AGB1) of the heterotrimeric G protein complex and play an important role in AGB1-dependent regulation of lateral root formation by affecting root auxin transport, auxin gradients and the steady-state levels of mRNA encoding the PIN-FORMED 2 and AUXIN 1 auxin transport facilitators. Auxin transport in aerial tissue follows different paths and utilizes different transporters than in roots; therefore, in the present study, we analyzed whether NDL proteins play an important role in AGB1-dependent, auxin-mediated meristem development. Expression levels of NDL gene family members need to be tightly regulated, and altered expression (both over-expression and down-regulation) confers ectopic growth. Over-expression of NDL1 disrupts vegetative and reproductive organ development. Reduced expression of the NDL gene family members results in asymmetric leaf emergence, twinning of rosette leaves, defects in leaf formation, and abnormal silique distribution. Reduced expression of the NDL genes in the agb1-2 (null allele) mutant rescues some of the abnormal phenotypes, such as silique morphology, silique distribution, and peduncle angle, suggesting that proper levels of NDL proteins are maintained by AGB1. We found that all of these abnormal aerial phenotypes due to altered NDL expression were associated with increases in basipetal auxin transport, altered auxin maxima and altered MAX2 expression within the inflorescence stem. NDL proteins, together with AGB1, act as positive regulators of meristem initiation and branching. AGB1 and NDL1 positively regulate basipetal inflorescence auxin transport and modulate MAX2 expression in shoots, which in turn regulates organ and lateral meristem formation by the establishment and maintenance of auxin gradients.

  16. N-MYC down-regulated-like proteins regulate meristem initiation by modulating auxin transport and MAX2 expression.

    Directory of Open Access Journals (Sweden)

    Yashwanti Mudgil

    Full Text Available N-MYC down-regulated-like (NDL proteins interact with the Gβ subunit (AGB1 of the heterotrimeric G protein complex and play an important role in AGB1-dependent regulation of lateral root formation by affecting root auxin transport, auxin gradients and the steady-state levels of mRNA encoding the PIN-FORMED 2 and AUXIN 1 auxin transport facilitators. Auxin transport in aerial tissue follows different paths and utilizes different transporters than in roots; therefore, in the present study, we analyzed whether NDL proteins play an important role in AGB1-dependent, auxin-mediated meristem development.Expression levels of NDL gene family members need to be tightly regulated, and altered expression (both over-expression and down-regulation confers ectopic growth. Over-expression of NDL1 disrupts vegetative and reproductive organ development. Reduced expression of the NDL gene family members results in asymmetric leaf emergence, twinning of rosette leaves, defects in leaf formation, and abnormal silique distribution. Reduced expression of the NDL genes in the agb1-2 (null allele mutant rescues some of the abnormal phenotypes, such as silique morphology, silique distribution, and peduncle angle, suggesting that proper levels of NDL proteins are maintained by AGB1. We found that all of these abnormal aerial phenotypes due to altered NDL expression were associated with increases in basipetal auxin transport, altered auxin maxima and altered MAX2 expression within the inflorescence stem.NDL proteins, together with AGB1, act as positive regulators of meristem initiation and branching. AGB1 and NDL1 positively regulate basipetal inflorescence auxin transport and modulate MAX2 expression in shoots, which in turn regulates organ and lateral meristem formation by the establishment and maintenance of auxin gradients.

  17. A generalized model for optimal transport of images including dissipation and density modulation

    KAUST Repository

    Maas, Jan; Rumpf, Martin; Schö nlieb, Carola; Simon, Stefan

    2015-01-01

    transport to strongly dissipative dynamics. For this model a robust and effective variational time discretization of geodesic paths is proposed. This requires to minimize a discrete path energy consisting of a sum of consecutive image matching functionals

  18. A comparative study of pH modulation and trace elements of various fruit juices on enamel erosion: An in vitro study

    Directory of Open Access Journals (Sweden)

    S.V.S.G Nirmala

    2011-01-01

    Full Text Available Fruit juices are popular worldwide with children of all ages as they are sweet and perceived to be healthful. This in vitro study was sought to measure pH of 10 different fruit juices, to find out possible erosive effects on human dental enamel of 40 extracted sound premolars and also to measure fluoride and trace elements of these juices. The estimation of pH of fruit juices was done by using Systronic upH 362 pH meter. The erosive effects of fruit juices were tested by using polarized light microscope. Orion electrode was used to measure fluoride. The trace elements were estimated by using Atomic Absorption Spectrophotometer No. 6501F. The pH values in different juices were observed at different levels, and pH values of these juices were more acidic than baseline after 24 hours. As the time increased, the erosion effect became more in pineapple; grape and sugarcane juices, and they had more cariogenic trace elements like selenium, iron and manganese. So, these juices were found to be cariogenic. To conclude, orange, mousambi, mango, pomegranate, apple, chikku and watermelon juices had no erosive effect on the human enamel, with the presence of highest amount of trace elements like fluoride and phosphorous which are considered as strongly cariostatic.

  19. Design of a mixed ionic/electronic conducting oxygen transport membrane pilot module

    Energy Technology Data Exchange (ETDEWEB)

    Pfaff, E.M.; Kaletsch, A.; Broeckmann, C. [RWTH Aachen University, IWM, Aachen (Germany)

    2012-03-15

    In the last years, a lot of ceramic materials were developed that, at higher temperatures, have a high electrical conductivity and a high conductivity of oxygen ions. Such mixed ionic/electronic conductors can be used to produce high-purity oxygen. This work focuses on the realization of a pilot membrane module, with BSCF (Ba{sub 0.5}Sr{sub 0.5}Co{sub 0.8}Fe{sub 0.2}O{sub 3-{delta}}) perovskite selected as the membrane material. An amount of 500 kg of powder was industrially fabricated, spray-granulized and pressed into tubes. The best operation conditions concerning energy consumption were calculated, and a module reactor was designed operating at 850 C, with an air pressure of 15-20 bar on the feed site and a low vacuum of about 0.8 bar on the permeate site. Special emphasis was placed on joining alternatives for ceramic tubes in metallic bottoms. A first laboratory module was tested with a membrane area of 1 m{sup 2} and then advanced to a pilot module with 570 tubes and a capability of more than 300 000 L of pure oxygen per day. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  20. ZnO nanoparticles modulate the ionic transport and voltage regulation of lysenin nanochannels.

    Science.gov (United States)

    Bryant, Sheenah L; Eixenberger, Josh E; Rossland, Steven; Apsley, Holly; Hoffmann, Connor; Shrestha, Nisha; McHugh, Michael; Punnoose, Alex; Fologea, Daniel

    2017-12-16

    The insufficient understanding of unintended biological impacts from nanomaterials (NMs) represents a serious impediment to their use for scientific, technological, and medical applications. While previous studies have focused on understanding nanotoxicity effects mostly resulting from cellular internalization, recent work indicates that NMs may interfere with transmembrane transport mechanisms, hence enabling contributions to nanotoxicity by affecting key biological activities dependent on transmembrane transport. In this line of inquiry, we investigated the effects of charged nanoparticles (NPs) on the transport properties of lysenin, a pore-forming toxin that shares fundamental features with ion channels such as regulation and high transport rate. The macroscopic conductance of lysenin channels greatly diminished in the presence of cationic ZnO NPs. The inhibitory effects were asymmetrical relative to the direction of the electric field and addition site, suggesting electrostatic interactions between ZnO NPs and a binding site. Similar changes in the macroscopic conductance were observed when lysenin channels were reconstituted in neutral lipid membranes, implicating protein-NP interactions as the major contributor to the reduced transport capabilities. In contrast, no inhibitory effects were observed in the presence of anionic SnO 2 NPs. Additionally, we demonstrate that inhibition of ion transport is not due to the dissolution of ZnO NPs and subsequent interactions of zinc ions with lysenin channels. We conclude that electrostatic interactions between positively charged ZnO NPs and negative charges within the lysenin channels are responsible for the inhibitory effects on the transport of ions. These interactions point to a potential mechanism of cytotoxicity, which may not require NP internalization.

  1. LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and Dimeric State

    Directory of Open Access Journals (Sweden)

    Claus U. Pietrzik

    2017-04-01

    Full Text Available The low-density lipoprotein receptor-related protein 1, LRP1, interacts with APP and affects its processing. This is assumed to be mostly caused by the impact of LRP1 on APP endocytosis. More recently, also an interaction of APP and LRP1 early in the secretory pathway was reported whereat retention of LRP1 in the ER leads to decreased APP cell surface levels and in turn, to reduced Aβ secretion. Here, we extended the biochemical and immunocytochemical analyses by showing via live cell imaging analyses in primary neurons that LRP1 and APP are transported only partly in common (one third but to a higher degree in distinct fast axonal transport vesicles. Interestingly, co-expression of LRP1 and APP caused a change of APP transport velocities, indicating that LRP1 recruits APP to a specific type of fast axonal transport vesicles. In contrast lowered levels of LRP1 facilitated APP transport. We further show that monomeric and dimeric APP exhibit similar transport characteristics and that both are affected by LRP1 in a similar way, by slowing down APP anterograde transport and increasing its endocytosis rate. In line with this, a knockout of LRP1 in CHO cells and in primary neurons caused an increase of monomeric and dimeric APP surface localization and in turn accelerated shedding by meprin β and ADAM10. Notably, a choroid plexus specific LRP1 knockout caused a much higher secretion of sAPP dimers into the cerebrospinal fluid compared to sAPP monomers. Together, our data show that LRP1 functions as a sorting receptor for APP, regulating its cell surface localization and thereby its processing by ADAM10 and meprin β, with the latter exhibiting a preference for APP in its dimeric state.

  2. The modulation of oceanic moisture transport by the hemispheric annular modes

    Directory of Open Access Journals (Sweden)

    Raquel eNieto

    2014-07-01

    Full Text Available Leaving aside the contribution made by recycling, it is the main oceanic moisture sources that are responsible for most of the precipitation that falls on the continents. The transport of moisture from these sources can be affected by large-scale variability according to the hemispheric annular modes. The influence of the two dominant modes of extratropical winter climate: the Northern and the Southern Annular Modes (NAM and SAM are herein investigated to assess how they affect the transport of moisture from the major oceanic moisture sources. A Lagrangian model was used, together with ERA-Interim reanalysis data (1979-2012, and differences between the composites of the six strongest higher and lower events observed for both phases of the two modes for the period were analysed. The method is able to reproduce the general pattern of known variations for both annular patterns. Lower values of the NAM Index are associated with the displacement of the storm track towards tropical latitudes. Thus, moisture transport is enhanced from the Northern Pacific towards the northeastern basin and from the Northern Atlantic and Mediterranean towards southern Europe. On the other hand, during higher values of NAM, moisture transport is favoured from the Northern Pacific towards eastern Asia, and moisture transport is enhanced from the Northern Atlantic towards the Caribbean Sea. In the Southern Hemisphere, during higher values of SAM more moisture is transported from the Atlantic and Indian oceanic sources southwards and eastwards than during the opposite phase. In this SAM phase it is also noted by an enhancement of moisture transport from the Coral Sea and Southern Pacific sources towards the Indian Ocean/West Pacific Warm Pool. Southeastern South America received more moisture from the Pacific and Atlantic sources during years with a lower SAM, episodes which also favoured the influx of moisture from the Southern Atlantic towards Africa, causing monsoon

  3. Effect of cytosolic pH on inward currents reveals structural characteristics of the proton transport cycle in the influenza A protein M2 in cell-free membrane patches of Xenopus oocytes.

    Directory of Open Access Journals (Sweden)

    Mattia L DiFrancesco

    Full Text Available Transport activity through the mutant D44A of the M2 proton channel from influenza virus A was measured in excised inside-out macro-patches of Xenopus laevis oocytes at cytosolic pH values of 5.5, 7.5 and 8.2. The current-voltage relationships reveal some peculiarities: 1. "Transinhibition", i.e., instead of an increase of unidirectional outward current with increasing cytosolic H(+ concentration, a decrease of unidirectional inward current was found. 2. Strong inward rectification. 3. Exponential rise of current with negative potentials. In order to interpret these findings in molecular terms, different kinetic models have been tested. The transinhibition basically results from a strong binding of H(+ to a site in the pore, presumably His37. This assumption alone already provides inward rectification and exponential rise of the IV curves. However, it results in poor global fits of the IV curves, i.e., good fits were only obtained for cytosolic pH of 8.2, but not for 7.5. Assuming an additional transport step as e.g. caused by a constriction zone at Val27 resulted in a negligible improvement. In contrast, good global fits for cytosolic pH of 7.5 and 8.2 were immediately obtained with a cyclic model. A "recycling step" implies that the protein undergoes conformational changes (assigned to Trp41 and Val27 during transport which have to be reset before the next proton can be transported. The global fit failed at the low currents at pHcyt = 5.5, as expected from the interference of putative transport of other ions besides H(+. Alternatively, a regulatory effect of acidic cytosolic pH may be assumed which strongly modifies the rate constants of the transport cycle.

  4. The study of neutron transport by oscillation method; Etude du transport des neutrons par la methode de modulation

    Energy Technology Data Exchange (ETDEWEB)

    Raievski, V

    1959-07-01

    The oscillation method is of very general use for studying the behavior of thermal neutrons in media. The main experiments are described and a general theory of them is given. This theory, which is presented in the first part, is established using the two-group approximation which has proved its efficiency in the case of thermal neutron piles. The validity of the two-group approximation is recalled. This allows definition of the meaning of the parameters used in the theory and which are measured in these experiments. The experiments carried out by this method are described, especially those performed at the Centre d'Etudes Nucleaires de Saclay where the method has been extensively used. These experiments are interpreted by means of the general theory given previously. In this way, the identity of parameters measured by this method and those given by the theory is proved. This is particularly conclusive is the case of the mean life of neutrons in a pile. (author) [French] La methode de modulation est un procede tres general d'etude des proprietes neutroniques des milieux contenant des neutrons thermiques. Le present rapport a pour but de decrire les principales de ces experiences et d'en donner une theorie generale. Cette theorie, exposee dans la premiere partie, est etablie dons le cadre de l'approximation a deux groupes de vitesse qui a prouve son efficacite dons le cas des piles a neutrons thermiques. Le domaine de validite de l'approximation a deux groupes est rappele au debut, ce qui permet de definir avec precision la signification des parametres qui entrent dons la theorie et qui font l'objet de ces mesures. La deuxieme partie decrit les experiences realisees, en particulier celles effectuees au Centre d'Etudes Nucleaires de Saclay ou la methode a ete considerablement developpee. Ces experiences sont interpretees dans le cadre de la theorie generale exposee precedemment. On prouve ainsi l'identite des parametres mesures par cette methode et de ceux figurant

  5. Potential pharmacokinetic role of organic cation transporters in modulating the transcorneal penetration of its substrates administered topically

    Science.gov (United States)

    Nirmal, J; Singh, S B; Biswas, N R; Thavaraj, V; Azad, R V; Velpandian, T

    2013-01-01

    Purpose We hypothesize organic cation transporters (OCT) may have a potential role in determining the pharmacokinetics and toxicity of organic cation drugs applied topically. Hence, in the present in vivo study, we attempted to evaluate the role of OCT in modulating the transport of its substrates after topical application. Methods New Zealand albino rabbits of either sex were used. Transcorneal penetration of OCT substrates tetraethylammonium and metformin after single instillation was evaluated in the absence and presence of OCT blockers (quinidine and atropine). Aqueous humor (AH) samples were collected through paracentesis amounting to 70–100 μl under topical anesthesia at various time intervals. The samples were subjected for estimation of both substrate as well as blocker concentrations using liquid chromatography mass spectrometry. Results Topical pre-treatment (30 min before substrate) of OCT blockers significantly decreased the transcorneal penetration of OCT substrates after single topical administration. The levels of blockers reaching AH in the presence of substrates were also modulated at 60 min after its administration as compared with its control. Conclusion OCT are functionally active in the uptake of their substrates from tear to AH. Therefore, OCT in the corneal epithelium may be positioned from apical to basolateral. When administering their substrates/blockers topically, both may be competing for OCT for their uptake across the cornea, thereby decreasing the corneal penetration. Hence OCT can have a potential pharmacokinetic role in modulating the ocular bioavailability of their substrates administered topically, which are used as ocular therapeutics. PMID:23846373

  6. Functional genetic variants in the vesicular monoamine transporter 1 (VMAT1) modulate emotion processing

    Science.gov (United States)

    Lohoff, Falk W.; Hodge, Rachel; Narasimhan, Sneha; Nall, Aleksandra; Ferraro, Thomas N.; Mickey, Brian J.; Heitzeg, Mary M.; Langenecker, Scott A.; Zubieta, Jon-Kar; Bogdan, Ryan; Nikolova, Yuliya S.; Drabant, Emily; Hariri, Ahmad R.; Bevilacqua, Laura; Goldman, David; Doyle, Glenn A.

    2012-01-01

    SUMMARY Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits, and risk for psychopathology. PMID:23337945

  7. Respiratory virus modulation of host nucleocytoplasmic transport; target for therapeutic intervention?

    Directory of Open Access Journals (Sweden)

    Leon eCaly

    2015-08-01

    Full Text Available The respiratory diseases caused by Rhinovirus, Respiratory Syncytial Virus and Influenza virus represent a large social and financial burden on healthcare worldwide. Although all three viruses have distinctly unique properties in terms of infection and replication, they share the ability to exploit/manipulate the host-cell nucleocytoplasmic transport system in order to replicate effectively and efficiently. This review outlines the various ways in which infection by these viruses impacts on the host nucleocytoplasmic transport system, and examples where inhibition thereof in turn decreases viral replication. The highly conserved nature of the nucleocytoplasmic transport system and the viral proteins that interact with it make this virus-host interface a prime candidate for the development of specific antiviral therapeutics in the future.

  8. A basic helix-loop-helix transcription factor, PhFBH4, regulates flower senescence by modulating ethylene biosynthesis pathway in petunia

    Science.gov (United States)

    The basic helix-loop-helix (bHLH) transcription factors (TFs) play important roles in regulating multiple biological processes in plants. However, there are few reports about the function of bHLHs in flower senescence. In this study, a bHLH TF, PhFBH4, was found to be dramatically upregulated during...

  9. Presence and function of dopamine transporter (DAT in stallion sperm: dopamine modulates sperm motility and acrosomal integrity.

    Directory of Open Access Journals (Sweden)

    Javier A Urra

    Full Text Available Dopamine is a catecholamine with multiple physiological functions, playing a key role in nervous system; however its participation in reproductive processes and sperm physiology is controversial. High dopamine concentrations have been reported in different portions of the feminine and masculine reproductive tract, although the role fulfilled by this catecholamine in reproductive physiology is as yet unknown. We have previously shown that dopamine type 2 receptor is functional in boar sperm, suggesting that dopamine acts as a physiological modulator of sperm viability, capacitation and motility. In the present study, using immunodetection methods, we revealed the presence of several proteins important for the dopamine uptake and signalling in mammalian sperm, specifically monoamine transporters as dopamine (DAT, serotonin (SERT and norepinephrine (NET transporters in equine sperm. We also demonstrated for the first time in equine sperm a functional dopamine transporter using 4-[4-(Dimethylaminostyryl]-N-methylpyridinium iodide (ASP(+, as substrate. In addition, we also showed that dopamine (1 mM treatment in vitro, does not affect sperm viability but decreases total and progressive sperm motility. This effect is reversed by blocking the dopamine transporter with the selective inhibitor vanoxerine (GBR12909 and non-selective inhibitors of dopamine reuptake such as nomifensine and bupropion. The effect of dopamine in sperm physiology was evaluated and we demonstrated that acrosome integrity and thyrosine phosphorylation in equine sperm is significantly reduced at high concentrations of this catecholamine. In summary, our results revealed the presence of monoamine transporter DAT, NET and SERT in equine sperm, and that the dopamine uptake by DAT can regulate sperm function, specifically acrosomal integrity and sperm motility.

  10. Modeling of carrier transport in multi-quantum-well p-i-n modulators

    DEFF Research Database (Denmark)

    Højfeldt, Sune; Mørk, Jesper

    2002-01-01

    The dynamical properties of InGaAsP multi-quantum-well electroabsorption modulators are investigated using a comprehensive numerical device model. We calculate the time-dependent sweep-out of photo-generated carriers and the corresponding time-dependent absorption change. The sweep-out is influen......The dynamical properties of InGaAsP multi-quantum-well electroabsorption modulators are investigated using a comprehensive numerical device model. We calculate the time-dependent sweep-out of photo-generated carriers and the corresponding time-dependent absorption change. The sweep......-out is influenced by carriers being recaptured into subsequent wells as they move towards the contacts. This process drastically increases the sweep-out time in our ten-well structure (similar to25 ps) compared to the pure drift-time (similar to1 ps). We also compare the saturation properties of two components...

  11. Stability and structure of the membrane protein transporter Ffh is modulated by substrates and lipids

    DEFF Research Database (Denmark)

    Reinau, Marika Ejby; Otzen, Daniel

    2009-01-01

    the apoprotein. Escherichia coli lipid and DOPG (and to a smaller extent DOPC) increase Ffh's α-helical content, possibly related to Ffh's role in guiding membrane proteins to the membrane. Binding is largely mediated by electrostatic interactions but does not protect Ffh against trypsinolysis. We conclude...... that Ffh is a structurally flexible and dynamic protein whose stability is significantly modulated by the environment. © 2009 Elsevier Inc. All rights reserved....

  12. CLM4-BeTR, a generic biogeochemical transport and reaction module for CLM4: model development, evaluation, and application

    Directory of Open Access Journals (Sweden)

    J. Y. Tang

    2013-01-01

    Full Text Available To improve regional and global biogeochemistry modeling and climate predictability, we have developed a generic reactive transport module for the land model CLM4 (called CLM4-BeTR (Biogeochemical Transport and Reactions. CLM4-BeTR represents the transport, interactions, and biotic and abiotic transformations of an arbitrary number of tracers (aka chemical species in an arbitrary number of phases (e.g., dissolved, gaseous, sorbed, aggregate. An operator splitting approach was employed and consistent boundary conditions were derived for each modeled sub-process. Aqueous tracer fluxes, associated with hydrological processes such as surface run-on and run-off, belowground drainage, and ice to liquid conversion were also computed consistently with the bulk water fluxes calculated by the soil physics module in CLM4. The transport code was evaluated and found in good agreement with several analytical test cases using a time step of 30 min. The model was then applied at the Harvard Forest site with a representation of depth-dependent belowground biogeochemistry. The results indicated that, at this site, (1 CLM4-BeTR was able to simulate soil–surface CO2 effluxes and soil CO2 profiles accurately; (2 the transient surface CO2 effluxes calculated based on the tracer transport mechanism were in general not equal to the belowground CO2 production rates with the magnitude of the difference being a function of averaging timescale and site conditions: differences were large (−20 ~ 20% on hourly, smaller (−5 ~ 5% at daily timescales, and persisted to the monthly timescales with a smaller magnitude (<4%; (3 losses of CO2 through processes other than surface gas efflux were less than 1% of the overall soil respiration; and (4 the contributions of root respiration and heterotrophic respiration have distinct temporal signals in surface CO2 effluxes and soil CO2 concentrations. The

  13. Modulation of cholesterol transport by maternal hypercholesterolemia in human full-term placenta.

    Directory of Open Access Journals (Sweden)

    Ran Zhang

    Full Text Available The significance of maternal cholesterol transporting to the fetus under normal as well as pathological circumstances is less understood. The objective of this study was to observe the effects of maternal hypercholesterolemia on placental cholesterol transportation. Human full-time placenta, maternal and venous cord blood were sampled at delivery from the pregnant women with serum total cholesterol (TC concentrations at third trimester higher than 7.25 mM (n = 19 and the pregnant women with normal TC concentrations (n = 19. Serum lipids and expression of genes related to cholesterol transportation were measured by western blot or real-time PCR. The results indicated that serum TC, high density lipoprotein cholesterol (HDL-C, and low density lipoprotein cholesterol (LDL-C levels were significantly increased, in pregnancies, but decreased in cord blood in hypercholesterolemic group compared to the matched control group. All the subjects were no-drinking, non-smoker, and gestational disease free. The mRNA expression of lipoprotein receptors, including LDLR and VLDLR were significantly increased, while the protein expression of PCSK9 was significantly increased in hypercholesterolemic placenta. In conclusion, maternal hypercholesterolemia might decrease the transportation of cholesterol from mother to fetus because of the high levels of PCSK9 protein expression.

  14. St. John's Wort constituents modulate P-glycoprotein transport activity at the blood-brain barrier.

    NARCIS (Netherlands)

    Ott, M.; Huls, M.; Cornelius, M.G.; Fricker, G.

    2010-01-01

    PURPOSE: The purpose of this study was to investigate the short-term signaling effects of St. John's Wort (SJW) extract and selected SJW constituents on the blood-brain barrier transporter P-glycoprotein and to describe the role of PKC in the signaling. METHODS: Cultured porcine brain capillary

  15. A generalized model for optimal transport of images including dissipation and density modulation

    KAUST Repository

    Maas, Jan

    2015-11-01

    © EDP Sciences, SMAI 2015. In this paper the optimal transport and the metamorphosis perspectives are combined. For a pair of given input images geodesic paths in the space of images are defined as minimizers of a resulting path energy. To this end, the underlying Riemannian metric measures the rate of transport cost and the rate of viscous dissipation. Furthermore, the model is capable to deal with strongly varying image contrast and explicitly allows for sources and sinks in the transport equations which are incorporated in the metric related to the metamorphosis approach by Trouvé and Younes. In the non-viscous case with source term existence of geodesic paths is proven in the space of measures. The proposed model is explored on the range from merely optimal transport to strongly dissipative dynamics. For this model a robust and effective variational time discretization of geodesic paths is proposed. This requires to minimize a discrete path energy consisting of a sum of consecutive image matching functionals. These functionals are defined on corresponding pairs of intensity functions and on associated pairwise matching deformations. Existence of time discrete geodesics is demonstrated. Furthermore, a finite element implementation is proposed and applied to instructive test cases and to real images. In the non-viscous case this is compared to the algorithm proposed by Benamou and Brenier including a discretization of the source term. Finally, the model is generalized to define discrete weighted barycentres with applications to textures and objects.

  16. Modulating the Surface State of SiC to Control Carrier Transport in Graphene/SiC.

    Science.gov (United States)

    Jia, Yuping; Sun, Xiaojuan; Shi, Zhiming; Jiang, Ke; Liu, Henan; Ben, Jianwei; Li, Dabing

    2018-05-28

    Silicon carbide (SiC) with epitaxial graphene (EG/SiC) shows a great potential in the applications of electronic and photoelectric devices. The performance of devices is primarily dependent on the interfacial heterojunction between graphene and SiC. Here, the band structure of the EG/SiC heterojunction is experimentally investigated by Kelvin probe force microscopy. The dependence of the barrier height at the EG/SiC heterojunction to the initial surface state of SiC is revealed. Both the barrier height and band bending tendency of the heterojunction can be modulated by controlling the surface state of SiC, leading to the tuned carrier transport behavior at the EG/SiC interface. The barrier height at the EG/SiC(000-1) interface is almost ten times that of the EG/SiC(0001) interface. As a result, the amount of carrier transport at the EG/SiC(000-1) interface is about ten times that of the EG/SiC(0001) interface. These results offer insights into the carrier transport behavior at the EG/SiC heterojunction by controlling the initial surface state of SiC, and this strategy can be extended in all devices with graphene as the top layer. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Ion Transport by Ameloblasts during Amelogenesis.

    Science.gov (United States)

    Bronckers, A L J J

    2017-03-01

    Hypomineralization of developing enamel is associated with changes in ameloblast modulation during the maturation stage. Modulation (or pH cycling) involves the cyclic transformation of ruffle-ended (RE) ameloblasts facing slightly acidic enamel into smooth-ended (SE) ameloblasts near pH-neutral enamel. The mechanism of ameloblast modulation is not clear. Failure of ameloblasts of Cftr-null and anion exchanger 2 ( Ae2)-null mice to transport Cl - into enamel acidifies enamel, prevents modulation, and reduces mineralization. It suggests that pH regulation is critical for modulation and for completion of enamel mineralization. This report presents a review of the major types of transmembrane molecules that ameloblasts express to transport calcium to form crystals and bicarbonates to regulate pH. The type of transporter depends on the developmental stage. Modulation is proposed to be driven by the pH of enamel fluid and the compositional and/or physicochemical changes that result from increased acidity, which may turn RE ameloblasts into SE mode. Amelogenins delay outgrowth of crystals and keep the intercrystalline space open for diffusion of mineral ions into complete depth of enamel. Modulation enables stepwise removal of amelogenins from the crystal surface, their degradation, and removal from the enamel. Removal of matrix allows slow expansion of crystals. Modulation also reduces the stress that ameloblasts experience when exposed to high acid levels generated by mineral formation or by increased intracellular Ca 2+ . By cyclically interrupting Ca 2+ transport by RE ameloblasts and their transformation into SE ameloblasts, proton production ceases shortly and enables the ameloblasts to recover. Modulation also improves enamel crystal quality by selectively dissolving immature Ca 2+ -poor crystals, removing impurities as Mg 2+ and carbonates, and recrystallizing into more acid-resistant crystals.

  18. The KCNQ5 potassium channel from mouse: a broadly expressed M-current like potassium channel modulated by zinc, pH, and volume changes

    DEFF Research Database (Denmark)

    Jensen, Henrik Sindal; Callø, Kirstine; Jespersen, Thomas

    2005-01-01

    H-dependent potentiation by Zn2+ (EC50 = 21.8 microM at pH 7.4), inhibition by acidification (IC50 = 0.75 microM; pKa = 6.1), and regulation by small changes in cell volume. Furthermore, the channels are activated by the anti-convulsant drug retigabine (EC50 = 2.0 microM) and inhibited by the M-current blockers...... and hippocampus. This study shows that murine KCNQ5 channels, in addition to sharing biophysical and pharmacological characteristics with the human ortholog, are tightly regulated by physiological stimuli such as changes in extracellular Zn2+, pH, and tonicity, thus adding to the complex regulation...

  19. Modulation of microenvironmental pH for dual release and reduced in vivo gastrointestinal bleeding of aceclofenac using hydroxypropyl methylcellulose-based bilayered matrix tablet.

    Science.gov (United States)

    Kang, Won-Ho; Nguyen, Hien Van; Park, Chulhun; Choi, Youn-Woong; Lee, Beom-Jin

    2017-05-01

    This study was designed to develop a once-daily controlled-release matrix tablet of aceclofenac 200mg (AFC-CR) with dual release characteristics and to investigate the role of an alkalizer in enhancing drug solubility and reducing the occurrence of gastroduodenal mucosal lesions. Two formulation approaches were employed, namely a monolithic matrix tablet and a bilayered tablet. In vitro dissolution studies of AFC-CR tablets were carried out in simulated intestinal fluid (pH6.8 buffer). The in vivo pharmacokinetic studies and drug safety of the immediate-release reference tablet Airtal® 100mg (Daewoong Co., Korea) and the optimized AFC-CR tablet were compared in beagle dogs under fasted condition. The optimally selected AFC-CR formulation displayed the desired dual release characteristics in simulated intestinal fluid with satisfactory micromeritic properties. The swelling action of the optimal matrix tablet, which was visualized by near-infrared (NIR) chemical imaging, occurred rapidly following hydration. Incorporation of sodium carbonate (Na 2 CO 3 ) was found to enhance the release rate of the AFC-CR bilayered tablets at early stages and increase the microenvironmental pH (pH M ). A pharmacokinetic study in beagle dogs indicated a higher drug plasma concentration and a sustained-release pattern for the AFC-CR tablet compared to the Airtal® tablet. AFC-CR was also superior to Airtal® in terms of in vivo drug safety, since no beagle dog receiving AFC-CR experienced gastrointestinal bleeding. The significant enhancement of drug safety was attributed to the size reduction and the increase of pH M of drug particles by means of incorporation of the alkalizer. These findings provide a scientific rationale for developing a novel controlled-release matrix tablet with enhanced patient compliance and better pain control. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Linearized Optically Phase-Modulated Fiber Optic Links for Microwave Signal Transport

    Science.gov (United States)

    2009-03-03

    detectors (with internal 50- Ohm resistors) capable of 40-mA dc current per detector. With this link, the linearized SFDR would improve to 133 dB/Hz4/5...the IF) limitation on the signal. All calculations consider the 3dB power loss from the hybrid combiner and 6dB loss from parallel 50- Ohm resistors...283. [25] M. Nazarathy, J. Berger, A. Ley , I. Levi, and Y. Kagan, “Externally Modulated 80 Channel Am Catv Fiber-to-feeder Distribution System Over

  1. Edge modulation of electronics and transport properties of cliff-edge phosphorene nanoribbons

    Science.gov (United States)

    Guo, Caixia; Wang, Tianxing; Xia, Congxin; Liu, Yufang

    2017-12-01

    Based on the first-principles calculations, we study the electronic structures and transport properties of cliff-like edge phosphorene nanoribbons (CPNRs), considering different types of edge passivation. The band structures of bare CPNRs possess the metallic features; while hydrogen (H), fluorine (F), chlorine (Cl) and oxygen (O) atoms-passivated CPNRs are semiconductor materials, and the band gap values monotonically decrease when the ribbon width increases. Moreover, the H and F-passivated CPNRs exhibit the direct band gap characteristics, while the Cl and O-passivated cases show the features of indirect band gap. In addition, the edge passivated CPNRs are more energetically stable than bare edge case. Meanwhile, our results also show that the transport properties of the CPNRs can be obviously influenced by the different edge passivation.

  2. The endocannabinoid transport inhibitor AM404 differentially modulates recognition memory in rats depending on environmental aversiveness

    OpenAIRE

    Campolongo, Patrizia; Ratano, Patrizia; Manduca, Antonia; Scattoni, Maria L.; Palmery, Maura; Trezza, Viviana; Cuomo, Vincenzo

    2012-01-01

    Cannabinoid compounds may influence both emotional and cognitive processes depending on the level of environmental aversiveness at the time of drug administration. However, the mechanisms responsible for these responses remain to be elucidated. The present experiments investigated the effects induced by the endocannabinoid transport inhibitor AM404 (0.5-5 mg/kg, i.p.) on bothemotional and cognitive performances of rats tested in a Spatial Open Field task and subjected to different experimenta...

  3. Substrate-modulated unwinding of transmembrane helices in the NSS transporter LeuT.

    Science.gov (United States)

    Merkle, Patrick S; Gotfryd, Kamil; Cuendet, Michel A; Leth-Espensen, Katrine Z; Gether, Ulrik; Loland, Claus J; Rand, Kasper D

    2018-05-01

    LeuT, a prokaryotic member of the neurotransmitter:sodium symporter (NSS) family, is an established structural model for mammalian NSS counterparts. We investigate the substrate translocation mechanism of LeuT by measuring the solution-phase structural dynamics of the transporter in distinct functional states by hydrogen/deuterium exchange mass spectrometry (HDX-MS). Our HDX-MS data pinpoint LeuT segments involved in substrate transport and reveal for the first time a comprehensive and detailed view of the dynamics associated with transition of the transporter between outward- and inward-facing configurations in a Na + - and K + -dependent manner. The results suggest that partial unwinding of transmembrane helices 1/5/6/7 drives LeuT from a substrate-bound, outward-facing occluded conformation toward an inward-facing open state. These hitherto unknown, large-scale conformational changes in functionally important transmembrane segments, observed for LeuT in detergent-solubilized form and when embedded in a native-like phospholipid bilayer, could be of physiological relevance for the translocation process.

  4. Parasitic nematodes modulate PIN-mediated auxin transport to facilitate infection.

    Directory of Open Access Journals (Sweden)

    Wim Grunewald

    2009-01-01

    Full Text Available Plant-parasitic nematodes are destructive plant pathogens that cause significant yield losses. They induce highly specialized feeding sites (NFS in infected plant roots from which they withdraw nutrients. In order to establish these NFS, it is thought that the nematodes manipulate the molecular and physiological pathways of their hosts. Evidence is accumulating that the plant signalling molecule auxin is involved in the initiation and development of the feeding sites of sedentary plant-parasitic nematodes. Intercellular transport of auxin is essential for various aspects of plant growth and development. Here, we analysed the spatial and temporal expression of PIN auxin transporters during the early events of NFS establishment using promoter-GUS/GFP fusion lines. Additionally, single and double pin mutants were used in infection studies to analyse the role of the different PIN proteins during cyst nematode infection. Based on our results, we postulate a model in which PIN1-mediated auxin transport is needed to deliver auxin to the initial syncytial cell, whereas PIN3 and PIN4 distribute the accumulated auxin laterally and are involved in the radial expansion of the NFS. Our data demonstrate that cyst nematodes are able to hijack the auxin distribution network in order to facilitate the infection process.

  5. Parasitic nematodes modulate PIN-mediated auxin transport to facilitate infection.

    Science.gov (United States)

    Grunewald, Wim; Cannoot, Bernard; Friml, Jirí; Gheysen, Godelieve

    2009-01-01

    Plant-parasitic nematodes are destructive plant pathogens that cause significant yield losses. They induce highly specialized feeding sites (NFS) in infected plant roots from which they withdraw nutrients. In order to establish these NFS, it is thought that the nematodes manipulate the molecular and physiological pathways of their hosts. Evidence is accumulating that the plant signalling molecule auxin is involved in the initiation and development of the feeding sites of sedentary plant-parasitic nematodes. Intercellular transport of auxin is essential for various aspects of plant growth and development. Here, we analysed the spatial and temporal expression of PIN auxin transporters during the early events of NFS establishment using promoter-GUS/GFP fusion lines. Additionally, single and double pin mutants were used in infection studies to analyse the role of the different PIN proteins during cyst nematode infection. Based on our results, we postulate a model in which PIN1-mediated auxin transport is needed to deliver auxin to the initial syncytial cell, whereas PIN3 and PIN4 distribute the accumulated auxin laterally and are involved in the radial expansion of the NFS. Our data demonstrate that cyst nematodes are able to hijack the auxin distribution network in order to facilitate the infection process.

  6. Development and application of the microbial fate and transport module for the Agricultural Policy/Environmental eXtender (APEX) model

    Science.gov (United States)

    Hong, E.; Park, Y.; Muirhead, R.; Jeong, J.; Pachepsky, Y. A.

    2017-12-01

    Pathogenic microorganisms in recreational and irrigation waters remain the subject of concern. Water quality models are used to estimate microbial quality of water sources, to evaluate microbial contamination-related risks, to guide the microbial water quality monitoring, and to evaluate the effect of agricultural management on the microbial water quality. The Agricultural Policy/Environmental eXtender (APEX) is the watershed-scale water quality model that includes highly detailed representation of agricultural management. The APEX currently does not have microbial fate and transport simulation capabilities. The objective of this work was to develop the first APEX microbial fate and transport module that could use the APEX conceptual model of manure removal together with recently introduced conceptualizations of the in-stream microbial fate and transport. The module utilizes manure erosion rates found in the APEX. Bacteria survival in soil-manure mixing layer was simulated with the two-stage survival model. Individual survival patterns were simulated for each manure application date. Simulated in-stream microbial fate and transport processes included the reach-scale passive release of bacteria with resuspended bottom sediment during high flow events, the transport of bacteria from bottom sediment due to the hyporheic exchange during low flow periods, the deposition with settling sediment, and the two-stage survival. Default parameter values were available from recently published databases. The APEX model with the newly developed microbial fate and transport module was applied to simulate seven years of monitoring data for the Toenepi watershed in New Zealand. Based on calibration and testing results, the APEX with the microbe module reproduced well the monitored pattern of E. coli concentrations at the watershed outlet. The APEX with the microbial fate and transport module will be utilized for predicting microbial quality of water under various agricultural

  7. Developing and investigating a pure Monte-Carlo module for transient neutron transport analysis

    International Nuclear Information System (INIS)

    Mylonakis, Antonios G.; Varvayanni, M.; Grigoriadis, D.G.E.; Catsaros, N.

    2017-01-01

    Highlights: • Development and investigation of a Monte-Carlo module for transient neutronic analysis. • A transient module developed on the open-source Monte-Carlo static code OpenMC. • Treatment of delayed neutrons is inserted. • Simulation of precursors’ decay process is performed. • Transient analysis of simplified test-cases. - Abstract: In the field of computational reactor physics, Monte-Carlo methodology is extensively used in the analysis of static problems while the transient behavior of the reactor core is mostly analyzed using deterministic algorithms. However, deterministic algorithms make use of various approximations mainly in the geometric and energetic domain that may induce inaccuracy. Therefore, Monte-Carlo methodology which generally does not require significant approximations seems to be an attractive candidate tool for the analysis of transient phenomena. One of the most important constraints towards this direction is the significant computational cost; however since nowadays the available computational resources are continuously increasing, the potential use of the Monte-Carlo methodology in the field of reactor core transient analysis seems feasible. So far, very few attempts to employ Monte-Carlo methodology to transient analysis have been reported. Even more, most of those few attempts make use of several approximations, showing the existence of an “open” research field of great interest. It is obvious that comparing to static Monte-Carlo, a straight-forward physical treatment of a transient problem requires the temporal evolution of the simulated neutrons; but this is not adequate. In order to be able to properly analyze transient reactor core phenomena, the proper simulation of delayed neutrons together with other essential extensions and modifications is necessary. This work is actually the first step towards the development of a tool that could serve as a platform for research and development on this interesting but also

  8. Temperature modulates the effects of ocean acidification on intestinal ion transport in Atlantic cod, Gadus morhua

    Directory of Open Access Journals (Sweden)

    Marian Yong-An Hu

    2016-06-01

    Full Text Available CO2-driven seawater acidification has been demonstrated to enhance intestinal bicarbonate secretion rates in teleosts, leading to an increased release of CaCO3 under simulated ocean acidification scenarios. In this study, we investigated if increasing CO2 levels stimulate the intestinal acid–base regulatory machinery of Atlantic cod (Gadus morhua and whether temperatures at the upper limit of thermal tolerance stimulate or counteract ion regulatory capacities. Juvenile G. morhua were acclimated for four weeks to three CO2 levels (550, 1,200 and 2,200 μatm covering present and near-future natural variability, at optimum (10°C and summer maximum temperature (18°C, respectively. Immunohistochemical analyses revealed the subcellular localization of ion transporters, including Na+/K+-ATPase (NKA, Na+/H+-exchanger 3 (NHE3, Na+/HCO3- cotransporter (NBC1, pendrin-like Cl-/HCO3- exchanger (SLC26a6, V-type H+-ATPase subunit a (VHA and Cl- channel 3 (CLC3 in epithelial cells of the anterior intestine. At 10°C, proteins and mRNA were generally up-regulated for most transporters in the intestinal epithelium after acclimation to higher CO2 levels. This supports recent findings demonstrating increased intestinal HCO3- secretion rates in response to CO2 induced seawater acidification. At 18°C, mRNA expression and protein concentrations of most ion transporters remained unchanged or were even decreased, suggesting thermal compensation. This response may be energetically favorable to retain blood HCO3- levels to stabilize pHe, but may negatively affect intestinal salt and water resorption of marine teleosts in future oceans.

  9. Serotonin and Serotonin Transporters in the Adrenal Medulla: A Potential Hub for Modulation of the Sympathetic Stress Response.

    Science.gov (United States)

    Brindley, Rebecca L; Bauer, Mary Beth; Blakely, Randy D; Currie, Kevin P M

    2017-05-17

    Serotonin (5-HT) is an important neurotransmitter in the central nervous system where it modulates circuits involved in mood, cognition, movement, arousal, and autonomic function. The 5-HT transporter (SERT; SLC6A4) is a key regulator of 5-HT signaling, and genetic variations in SERT are associated with various disorders including depression, anxiety, and autism. This review focuses on the role of SERT in the sympathetic nervous system. Autonomic/sympathetic dysfunction is evident in patients with depression, anxiety, and other diseases linked to serotonergic signaling. Experimentally, loss of SERT function (SERT knockout mice or chronic pharmacological block) has been reported to augment the sympathetic stress response. Alterations to serotonergic signaling in the CNS and thus central drive to the peripheral sympathetic nervous system are presumed to underlie this augmentation. Although less widely recognized, SERT is robustly expressed in chromaffin cells of the adrenal medulla, the neuroendocrine arm of the sympathetic nervous system. Adrenal chromaffin cells do not synthesize 5-HT but accumulate small amounts by SERT-mediated uptake. Recent evidence demonstrated that 5-HT 1A receptors inhibit catecholamine secretion from adrenal chromaffin cells via an atypical mechanism that does not involve modulation of cellular excitability or voltage-gated Ca 2+ channels. This raises the possibility that the adrenal medulla is a previously unrecognized peripheral hub for serotonergic control of the sympathetic stress response. As a framework for future investigation, a model is proposed in which stress-evoked adrenal catecholamine secretion is fine-tuned by SERT-modulated autocrine 5-HT signaling.

  10. The effect of the series resistance in dye-sensitized solar cells explored by electron transport and back reaction using electrical and optical modulation techniques

    International Nuclear Information System (INIS)

    Liu Weiqing; Hu Linhua; Dai Songyuan; Guo Lei; Jiang Nianquan; Kou Dongxing

    2010-01-01

    The influence of the series resistance on the electron transport and recombination processes in dye-sensitized solar cells (DSC) has been investigated. The series resistances induced by some parts of DSC, such as the transparent conductive oxide (TCO), the electrolyte layer and the counter electrode, influence the performance of DSC. By combining three frequency-domain techniques, specifically electrochemical impedance spectroscopy (EIS), intensity modulated photocurrent spectroscopy (IMPS) and intensity modulated photovoltage spectroscopy (IMVS), we studied the relationship between the series resistance and the dynamic response of DSC. The results show that the series resistance induced by the TCO or counter electrode predominantly affects the electron transport under short circuit conditions and has no significant influence on the recombination under open circuit conditions. However, the resistance related to the electrolyte layer not only limits the carrier transport but also influences the recombination. Possible reasons for the influence of the series resistance on the electron transport and recombination processes in DSC are also discussed.

  11. Non-binary coded modulation for FMF-based coherent optical transport networks

    Science.gov (United States)

    Lin, Changyu

    The Internet has fundamentally changed the way of modern communication. Current trends indicate that high-capacity demands are not going to be saturated anytime soon. From Shannon's theory, we know that information capacity is a logarithmic function of signal-to-noise ratio (SNR), but a linear function of the number of dimensions. Ideally, we can increase the capacity by increasing the launch power, however, due to the nonlinear characteristics of silica optical fibers that imposes a constraint on the maximum achievable optical-signal-to-noise ratio (OSNR). So there exists a nonlinear capacity limit on the standard single mode fiber (SSMF). In order to satisfy never ending capacity demands, there are several attempts to employ additional degrees of freedom in transmission system, such as few-mode fibers (FMFs), which can dramatically improve the spectral efficiency. On the other hand, for the given physical links and network equipment, an effective solution to relax the OSNR requirement is based on forward error correction (FEC), as the response to the demands of high speed reliable transmission. In this dissertation, we first discuss the model of FMF with nonlinear effects considered. Secondly, we simulate the FMF based OFDM system with various compensation and modulation schemes. Thirdly, we propose tandem-turbo-product nonbinary byte-interleaved coded modulation (BICM) for next-generation high-speed optical transmission systems. Fourthly, we study the Q factor and mutual information as threshold in BICM scheme. Lastly, an experimental study of the limits of nonlinearity compensation with digital signal processing has been conducted.

  12. Short-term nutritional strategies before slaughter are effective in modulating the final pH and color of broiler breast meat.

    Science.gov (United States)

    Guardia, Sarah; Lessire, Michel; Corniaux, Alain; Métayer-Coustard, Sonia; Mercerand, Frédéric; Tesseraud, Sophie; Bouvarel, Isabelle; Berri, Cécile

    2014-07-01

    The poultry meat industry is faced with various quality issues related to variations in the ultimate pH of breast meat. The aim of this study was to evaluate the possibility to control breast ultimate pH by distributing finishing diets varying in amino acid (AA) and energy content for a short period before slaughter. Experimental diets were distributed to PM3 broilers on the last 3 d before slaughter (36 d of age). They consisted of a control (C) diet (3,150 kcal/kg; 200 g/kg of CP; 10.0 g/kg of true digestible Lys) with adequate amounts of AA other than Lys, 6 diets isocaloric to the control diet including 3 Lys-deficient (8.0 g/kg) diets with an adequate (Lys-/AA), low (Lys-/AA-), or high (Lys-/AA+) amount of other essential AA calculated in relation to Lys, and 3 Lys-rich (12.0 g/kg) diets with an adequate (Lys+/AA), low (Lys+/AA-), or high (Lys+/AA+) amount of other essential AA calculated in relation to Lys, and 2 diets isoproteic to C with a high (3,300 kcal/kg, E+) or low (3,000 kcal/kg, E-) energy content. Broiler feed consumption and growth performance were slightly affected by AA and energy content during the finishing period. Feed intake (33-36 d) was lower with the Lys+/AA+ and E+, and FCR between 24 and 36 d was higher with the Lys-/AA- and E- than with the C diet. Body weight at d 36 was lower in Lys-/AA-, Lys+/AA+, and E+ than in C, whereas the breast meat yield and abdominal fatness were not affected by diet. Lower pH values were observed in broilers fed Lys-deficient diets containing a high amount of other AA (Lys-/AA+) than in broilers fed diets containing low (AA-) or adequate (AA) amounts of other AA. This study shows that it is possible to alter the pH of breast meat by changing AA profile over a short period before slaughter, with limited impact on broiler growth and carcass composition. © 2014 Poultry Science Association Inc.

  13. Large modulation of carrier transport by grain-boundary molecular packing and microstructure in organic thin films

    KAUST Repository

    Rivnay, Jonathan

    2009-11-08

    Solution-processable organic semiconductors are central to developing viable printed electronics, and performance comparable to that of amorphous silicon has been reported for films grown from soluble semiconductors. However, the seemingly desirable formation of large crystalline domains introduces grain boundaries, resulting in substantial device-to-device performance variations. Indeed, for films where the grain-boundary structure is random, a few unfavourable grain boundaries may dominate device performance. Here we isolate the effects of molecular-level structure at grain boundaries by engineering the microstructure of the high-performance n-type perylenediimide semiconductor PDI8-CN 2 and analyse their consequences for charge transport. A combination of advanced X-ray scattering, first-principles computation and transistor characterization applied to PDI8-CN 2 films reveals that grain-boundary orientation modulates carrier mobility by approximately two orders of magnitude. For PDI8-CN 2 we show that the molecular packing motif (that is, herringbone versus slip-stacked) plays a decisive part in grain-boundary-induced transport anisotropy. The results of this study provide important guidelines for designing device-optimized molecular semiconductors. © 2009 Macmillan Publishers Limited. All rights reserved.

  14. OsPIN5b modulates rice (Oryza sativa) plant architecture and yield by changing auxin homeostasis, transport and distribution.

    Science.gov (United States)

    Lu, Guangwen; Coneva, Viktoriya; Casaretto, José A; Ying, Shan; Mahmood, Kashif; Liu, Fang; Nambara, Eiji; Bi, Yong-Mei; Rothstein, Steven J

    2015-09-01

    Plant architecture attributes such as tillering, plant height and panicle size are important agronomic traits that determine rice (Oryza sativa) productivity. Here, we report that altered auxin content, transport and distribution affect these traits, and hence rice yield. Overexpression of the auxin efflux carrier-like gene OsPIN5b causes pleiotropic effects, mainly reducing plant height, leaf and tiller number, shoot and root biomass, seed-setting rate, panicle length and yield parameters. Conversely, reduced expression of OsPIN5b results in higher tiller number, more vigorous root system, longer panicles and increased yield. We show that OsPIN5b is an endoplasmic reticulum (ER) -localized protein that participates in auxin homeostasis, transport and distribution in vivo. This work describes an example of an auxin-related gene where modulating its expression can simultaneously improve plant architecture and yield potential in rice, and reveals an important effect of hormonal signaling on these traits. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  15. User Instructions for the Systems Assessment Capability, Rev. 0, Computer Codes Volume 1: Inventory, Release, and Transport Modules

    International Nuclear Information System (INIS)

    Eslinger, Paul W.; Engel, David W.; Gerhardstein, Lawrence H.; Lopresti, Charles A.; Nichols, William E.; Strenge, Dennis L.

    2001-12-01

    One activity of the Department of Energy's Groundwater/Vadose Zone Integration Project is an assessment of cumulative impacts from Hanford Site wastes on the subsurface environment and the Columbia River. Through the application of a system assessment capability (SAC), decisions for each cleanup and disposal action will be able to take into account the composite effect of other cleanup and disposal actions. The SAC has developed a suite of computer programs to simulate the migration of contaminants (analytes) present on the Hanford Site and to assess the potential impacts of the analytes, including dose to humans, socio-cultural impacts, economic impacts, and ecological impacts. The general approach to handling uncertainty in the SAC computer codes is a Monte Carlo approach. Conceptually, one generates a value for every stochastic parameter in the code (the entire sequence of modules from inventory through transport and impacts) and then executes the simulation, obtaining an output value, or result. This document provides user instructions for the SAC codes that handle inventory tracking, release of contaminants to the environment, and transport of contaminants through the unsaturated zone, saturated zone, and the Columbia River

  16. Modulation of electronic transport properties in armchair phosphorene nanoribbons by doping and edge passivation.

    Science.gov (United States)

    Guo, Caixia; Wang, Tianxing; Xia, Congxin; Liu, Yufang

    2017-10-09

    The electronic structures and transport properties of group IV atoms (C, Si, Ge)-doped armchair phosphorene nanoribbons (APNRs) are investigated using first-principles calculations, considering different edge passivation. The results show that the C, Si, Ge dopants can induce the transition occur from semiconductor to metal in the APNRs. The negative differential resistance (NDR) behavior in the doped APNR system is robust with respect to the doping concentration and edge passivation type. However, their current peak positions and peak-to-valley ratio (PVR) values are correlated with doping concentration and edge passivation type. In particular, for the C, Si-doped APNRs, the low bias NDR behavior with the PVR (10 5 -10 8 ) can be observed when doping concentration is low in the APNRs with the F and H edge passivation. These results may play an important role for the fabrication of future low power consumption nano-electronic devices.

  17. Variation in the serotonin transporter gene modulates selective attention to threat.

    Science.gov (United States)

    Osinsky, Roman; Reuter, Martin; Küpper, Yvonne; Schmitz, Anja; Kozyra, Eva; Alexander, Nina; Hennig, Jürgen

    2008-08-01

    The 5-HTTLPR is an insertion/deletion polymorphism in the promoter region of the serotonin transporter gene. Prior research has revealed associations between the short-allele variant of this polymorphism, enhanced self-reported negative emotionality, and hypersensitivity of fear relevant neural circuits. In a sample of 50 healthy women we examined the role of 5-HTTLPR for cognitive-affective processing of phylogenetical fear-relevant stimuli (spiders) in a dot probe task. In contrast to homozygote long-allele carriers (ll), participants carrying at least 1 short allele (ss and sl) selectively shifted attention toward pictures of spiders, when these were presented for a duration of 2,000 ms. These results argue for an involvement of 5-HTTLPR in cognitive processing of threatening stimuli and thus, underpin its general role for individual differences in negative affect.

  18. Modulation of transport properties of RuO2 with 3d transition metals

    International Nuclear Information System (INIS)

    Music, Denis; Chen, Yen-Ting; Geyer, Richard W; Bliem, Pascal; Schneider, Jochen M

    2014-01-01

    Using density functional theory, we have demonstrated that alloying of RuO 2 (P4 2 /mnm) with 3d transition metals (Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn) gives rise to a substantial increase in the Seebeck coefficient probably due to quantum confinement. As Fe yields the largest enhancement, it was selected for experimental verification. We synthesized combinatorial Ru–Fe–O thin films and subsequently measured their transport properties at elevated temperatures. The Fe-alloyed samples increase the Seebeck coefficient threefold with respect to the unalloyed RuO 2 specimen thereby verifying the theoretical prediction. The here obtained power factor of 274 μW K −2 m −1 is not only the largest reported value for RuO 2 based compounds but it also occurs at ∼600 °C thus increasing the Carnot efficiency significantly. (paper)

  19. Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4.

    Science.gov (United States)

    Pearson-Leary, J; Jahagirdar, V; Sage, J; McNay, E C

    2018-02-15

    The insulin-regulated glucose transporter, GluT4, is a key molecule in peripheral insulin signaling. Although GluT4 is abundantly expressed in neurons of specific brain regions such as the hippocampus, the functional role of neuronal GluT4 is unclear. Here, we used pharmacological inhibition of GluT4-mediated glucose uptake to determine whether GluT4 mediates insulin-mediated glucose uptake in the hippocampus. Consistent with previous reports, we found that glucose utilization increased in the dorsal hippocampus of male rats during spontaneous alternation (SA), a hippocampally-mediated spatial working memory task. We previously showed that insulin signaling within the hippocampus is required for processing this task, and that administration of exogenous insulin enhances performance. At baseline levels of hippocampal insulin, inhibition of GluT4-mediated glucose uptake did not affect SA performance. However, inhibition of an upstream regulator of GluT4, Akt, did impair SA performance. Conversely, when a memory-enhancing dose of insulin was delivered to the hippocampus prior to SA-testing, inhibition of GluT4-mediated glucose transport prevented cognitive enhancement. These data suggest that baseline hippocampal cognitive processing does not require functional hippocampal GluT4, but that cognitive enhancement by supra-baseline insulin does. Consistent with these findings, we found that in neuronal cell culture, insulin increases glucose utilization in a GluT4-dependent manner. Collectively, these data demonstrate a key role for GluT4 in transducing the procognitive effects of elevated hippocampal insulin. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Affective neural responses modulated by serotonin transporter genotype in clinical anxiety and depression.

    Directory of Open Access Journals (Sweden)

    Desmond J Oathes

    Full Text Available Serotonin transporter gene variants are known to interact with stressful life experiences to increase chances of developing affective symptoms, and these same variants have been shown to influence amygdala reactivity to affective stimuli in non-psychiatric populations. The impact of these gene variants on affective neurocircuitry in anxiety and mood disorders has been studied less extensively. Utilizing a triallelic assay (5-HTTLPR and rs25531 to assess genetic variation linked with altered serotonin signaling, this fMRI study investigated genetic influences on amygdala and anterior insula activity in 50 generalized anxiety disorder patients, 26 of whom also met DSM-IV criteria for social anxiety disorder and/or major depressive disorder, and 39 healthy comparison subjects. A Group x Genotype interaction was observed for both the amygdala and anterior insula in a paradigm designed to elicit responses in these brain areas during the anticipation of and response to aversive pictures. Patients who are S/L(G carriers showed less activity than their L(A/L(A counterparts in both regions and less activity than S/L(G healthy comparison subjects in the amygdala. Moreover, patients with greater insula responses reported higher levels of intolerance of uncertainty, an association that was particularly pronounced for patients with two LA alleles. A genotype effect was not established in healthy controls. These findings link the serotonin transporter gene to affective circuitry findings in anxiety and depression psychopathology and further suggest that its impact on patients may be different from effects typically observed in healthy populations.

  1. Dopamine transporter gene variation modulates activation of striatum in youth with ADHD.

    Science.gov (United States)

    Bédard, Anne-Claude; Schulz, Kurt P; Cook, Edwin H; Fan, Jin; Clerkin, Suzanne M; Ivanov, Iliyan; Halperin, Jeffrey M; Newcorn, Jeffrey H

    2010-11-15

    Polymorphisms in the 3'UTR variable number tandem repeat (VNTR) of exon 15 of the dopamine transporter gene (DAT1) have been linked to attention-deficit hyperactivity disorder (ADHD); moreover, variability in DAT1 3'UTR genotype may contribute to both heterogeneity of the ADHD phenotype and differences in response to stimulant medications. The impact of this VNTR on neuronal function in individuals with ADHD remains unclear despite evidence that the polymorphisms influence dopamine transporter expression. Thus, we used event-related functional magnetic resonance imaging to examine the impact of DAT1 3'UTR genotype on brain activation during response inhibition in unmedicated children and adolescents with ADHD. Twenty-one youth with ADHD who were homozygous for the 10-repeat (10R) allele of the DAT1 3'UTR and 12 youth who were carriers of the 9-repeat (9R) allele were scanned while they performed a Go/No-Go task. Response inhibition was modeled by contrasting activation during correct No-Go trials versus correct Go trials. Participants who were homozygous for the DAT1 3'UTR 10R allele and those who had a single 9R allele did not differ on percent of trials with successful inhibition, which was the primary measure of inhibitory control. Yet, youth with the DAT1 3'UTR 10R/10R genotype had significantly greater inhibitory control-related activation than those with one 9R allele in the left striatum, right dorsal premotor cortex, and bilaterally in the temporoparietal cortical junction. These findings provide preliminary evidence that neural activity related to inhibitory control may differ as a function of DAT1 3'UTR genotype in youth with ADHD. Copyright 2009 Elsevier Inc. All rights reserved.

  2. Fluoride-induced modulation of ionic transport in asymmetric nanopores functionalized with "caged" fluorescein moieties.

    Science.gov (United States)

    Ali, Mubarak; Ahmed, Ishtiaq; Ramirez, Patricio; Nasir, Saima; Cervera, Javier; Niemeyer, Christof M; Ensinger, Wolfgang

    2016-04-28

    We demonstrate experimentally and theoretically a nanofluidic fluoride sensing device based on a single conical pore functionalized with "caged" fluorescein moieties. The nanopore functionalization is based on an amine-terminated fluorescein whose phenolic hydroxyl groups are protected with tert-butyldiphenylsilyl (TBDPS) moieties. The protected fluorescein (Fcn-TBDPS-NH2) molecules are then immobilized on the nanopore surface via carbodiimide coupling chemistry. Exposure to fluoride ions removes the uncharged TBDPS moieties due to the fluoride-promoted cleavage of the silicon-oxygen bond, leading to the generation of negatively charged groups on the fluorescein moieties immobilized onto the pore surface. The asymmetrical distribution of these groups along the conical nanopore leads to the electrical rectification observed in the current-voltage (I-V) curve. On the contrary, other halides and anions are not able to induce any significant ionic rectification in the asymmetric pore. In each case, the success of the chemical functionalization and deprotection reactions is monitored through the changes observed in the I-V curves before and after the specified reaction step. The theoretical results based on the Nernst-Planck and Poisson equations further demonstrate the validity of an experimental approach to fluoride-induced modulation of nanopore current rectification behaviour.

  3. Modulation of electrogenic transport processes in the porcine proximal colon by enteric neurotransmitters.

    Science.gov (United States)

    Pfannkuche, H; Mauksch, A; Gäbel, G

    2012-06-01

    The aim of our study was to evaluate the involvement of essential pro- and antisecretory neurotransmitters in regulation of secretion in porcine proximal colon. Choline acetyltransferase (ChAT), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), substance P (SP), somatostatin (SOM) and neuropeptide Y (NPY) were located immunohistochemically in the epithelium and subepithelial layer. Modulation of epithelial secretion was studied in Ussing chambers. Application of carbachol (CA), sodium nitroprussid (SNP), VIP and SP but not of NPY or SOM resulted in a chloride dependent increase in short circuit current (I(sc) ). I(sc) increase induced by CA, VIP or SNP was not altered by preincubation with tetrodotoxin or indomethacin. In contrast, SP-induced I(sc) increase was diminished by preincubation with tetrodotoxin, indomethacin, L-nitro-arginin-methyl-ester, and atropine but not hexamethonium. Simultaneous application of CA and VIP, or CA and SNP increased the I(sc) stronger as expected. Applying SP/CA led to a smaller increase in I(sc) as calculated. It is concluded that mainly prosecretory neurotransmitters are involved in regulation of colonic secretion. Cross-potentiations of acetylcholine and nitric oxide and acetylcholine and VIP suggest activation of different intracellular cascades. Similar intracellular pathways may be stimulated by acetylcholine and SP, thus preventing an additive effect of the transmitters. © 2011 Blackwell Verlag GmbH.

  4. Fluorescence properties of the anti-tumour alkaloid luotonin A and new synthetic analogues: pH modulation as an approach to their fluorimetric quantitation in biological samples

    International Nuclear Information System (INIS)

    González-Ruiz, Víctor; González-Cuevas, Yamisley; Arunachalam, Sankaralingam; Martín, M. Antonia; Olives, Ana I.; Ribelles, Pascual; Ramos, M. Teresa; Menéndez, J. Carlos

    2012-01-01

    Luotonin A is an alkaloid structurally related to the natural anti-tumour agent camptothecin. The fluorescence behaviour of luotonin A and a series of six analogues is described in the present work. The influence of solvent polarity and pH on the native fluorescence properties of these alkaloids was studied, finding that in organic solvents or in aqueous solutions (pH 5.5–7.2) the neutral form of the luotonin derivatives emit in the region of 410–450 nm but, in both media, acidification to pH values below 3.0 causes a new emission band to appear at about 500 nm. An ESPT reaction occurs due to the protonation of the basic nitrogen atoms of the pentacyclic ring. Acid-base titrations of luotonin A and its derivatives in aqueous and acetonitrile media were carried out in order to determine their pK a ⁎ values which were around 2, showing these compounds to be very weak bases. In aqueous media, the absence of an iso-emissive point in the emission spectra suggests the existence of more than two species in the proton transfer equilibria. The basicity of the luotonin A derivatives is increased in organic media, and a good correlation between the pK a ⁎ values and the chemical structure was found. The protonation of luotonin A was also studied by 1 H-NMR and 13 C-NMR experiments, which proved the protonation of the nitrogen atoms at the positions 5 and 6 of the pentacyclic ring. The fluorescence quantum yields were determined in ethanol and in aqueous solutions under neutral and acidic conditions. The fluorescence quantum yields were higher in water for the case of the more polar compounds, and the opposite result was obtained for the more hydrophobic ones. The remarkable and interesting fluorescence properties of luotonin A prompted the development of its fluorimetric analytical quantitation, obtaining very good analytical features. - Highlights: ► This is the first study on the fluorescence properties of luotonin A analogues. ► Fluorescence and NMR experiments

  5. Fluorescence properties of the anti-tumour alkaloid luotonin A and new synthetic analogues: pH modulation as an approach to their fluorimetric quantitation in biological samples

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Ruiz, Victor; Gonzalez-Cuevas, Yamisley; Arunachalam, Sankaralingam [S. D. Quimica Analitica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid (Spain); Martin, M. Antonia, E-mail: mantonia@farm.ucm.es [S. D. Quimica Analitica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid (Spain); Olives, Ana I. [S. D. Quimica Analitica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid (Spain); Ribelles, Pascual; Ramos, M. Teresa; Menendez, J. Carlos [D. Quimica Organica y Farmaceutica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid (Spain)

    2012-09-15

    Luotonin A is an alkaloid structurally related to the natural anti-tumour agent camptothecin. The fluorescence behaviour of luotonin A and a series of six analogues is described in the present work. The influence of solvent polarity and pH on the native fluorescence properties of these alkaloids was studied, finding that in organic solvents or in aqueous solutions (pH 5.5-7.2) the neutral form of the luotonin derivatives emit in the region of 410-450 nm but, in both media, acidification to pH values below 3.0 causes a new emission band to appear at about 500 nm. An ESPT reaction occurs due to the protonation of the basic nitrogen atoms of the pentacyclic ring. Acid-base titrations of luotonin A and its derivatives in aqueous and acetonitrile media were carried out in order to determine their pK{sub a}{sup Low-Asterisk} values which were around 2, showing these compounds to be very weak bases. In aqueous media, the absence of an iso-emissive point in the emission spectra suggests the existence of more than two species in the proton transfer equilibria. The basicity of the luotonin A derivatives is increased in organic media, and a good correlation between the pK{sub a}{sup Low-Asterisk} values and the chemical structure was found. The protonation of luotonin A was also studied by {sup 1}H-NMR and {sup 13}C-NMR experiments, which proved the protonation of the nitrogen atoms at the positions 5 and 6 of the pentacyclic ring. The fluorescence quantum yields were determined in ethanol and in aqueous solutions under neutral and acidic conditions. The fluorescence quantum yields were higher in water for the case of the more polar compounds, and the opposite result was obtained for the more hydrophobic ones. The remarkable and interesting fluorescence properties of luotonin A prompted the development of its fluorimetric analytical quantitation, obtaining very good analytical features. - Highlights: Black-Right-Pointing-Pointer This is the first study on the fluorescence

  6. Transportation

    National Research Council Canada - National Science Library

    Adams, James; Carr, Ron; Chebl, Maroun; Coleman, Robert; Costantini, William; Cox, Robert; Dial, William; Jenkins, Robert; McGovern, James; Mueller, Peter

    2006-01-01

    ...., trains, ships, etc.) and maximizing intermodal efficiency. A healthy balance must be achieved between the flow of international commerce and security requirements regardless of transportation mode...

  7. Sulfate transport kinetics and toxicity are modulated by sodium in aquatic insects.

    Science.gov (United States)

    Scheibener, Shane; Conley, Justin M; Buchwalter, David

    2017-09-01

    The salinization of freshwater ecosystems is emerging as a major ecological issue. Several anthropogenic causes of salinization (e.g. surface coal mining, hydro-fracking, road de-icing, irrigation of arid lands, etc.) are associated with biodiversity losses in freshwater ecosystems. Because insects tend to dominate freshwater ecology, it is important that we develop a better understanding of how and why different species respond to salinity matrices dominated by different major ions. This study builds upon previous work demonstrating that major ion toxicity to the mayfly Neocloeon triangulifer was apparently due to the ionic composition of water rather than specific conductance. Synthetic waters with low Ca:Mg ratios and high SO 4 :Na ratios produced toxicity, whereas waters with higher Ca:Mg ratios and lower SO 4 :Na ratios were not toxic to mayflies at comparable conductivities. Here we used a radiotracer approach to show that Mg did not competitively exclude Ca uptake at environmentally realistic ratios in 4 aquatic insect species. We characterized SO 4 uptake kinetics in 5 mayflies and assessed the influence of different ions on SO 4 uptake. Dual label experiments show an inverse relationship between SO 4 and Na transport rates as SO 4 was held constant and Na was increased, suggesting that Na (and not Cl or HCO 3 ) is antagonistic to SO 4 transport. Based on this observation, we tested the hypothesis that increasing Na would protect against SO 4 induced toxicity in a Na-dependent manner. Increasing Na from 0.7 to 10.9mM improved 96-h survivorship associated with 20.8mM SO 4 from 44% to 73% in a concentration dependent manner. However, when Na reached 21.8mM, survivorship decreased to 16%, suggesting that other interactive effects of major ions caused toxicity under those conditions. Thus, the combination of elevated sulfate and low sodium commonly observed in streams affected by mountaintop coal mining has the potential to cause toxicity in sensitive aquatic

  8. Modulation of Human Serotonin Transporter Expression by 5-HTTLPR in Colon Cells

    Directory of Open Access Journals (Sweden)

    Tewin Tencomnao

    2011-10-01

    Full Text Available Serotonin (5-HT is a monoamine neurotransmitter and plays important roles in several of the human body’s systems. Known as a primary target for psychoactive drug development, the 5-HT transporter (5-HTT, SERT plays a critical role in the regulation of serotonergic function by reuptaking 5-HT. The allelic variation of 5-HTT expression is caused by functional gene promoter polymorphism with two principal variant alleles, 5-HTT gene-linked polymorphic region (5-HTTLPR. It has been demonstrated that 5-HTTLPR is associated with numerous neuropsychiatric disorders. The functional roles of 5-HTTLPR have been reported in human choriocarcinoma (JAR, lymphoblast and raphe cells. To date, the significance of 5-HTTLPR in gastrointestinal tract-derived cells has never been elucidated. Thus, the impact of 5-HTTLPR on 5-HTT transcription was studied in SW480 human colon carcinoma cells, which were shown to express 5-HTT. We found 42-bp fragment in long (L allele as compared to short (S allele, and this allelic difference resulted in 2-fold higher transcriptional efficiency of L allele (P < 0.05 as demonstrated using a functional reporter gene assay. Nevertheless, the transcriptional effect of estrogen and glucocorticoid on 5-HTT expression via 5-HTTLPR was not found in this cell line. Our study was the first to demonstrate the molecular role of this allelic variation in gastrointestinal tract cells.

  9. Modulation of the platelet serotonin transporter by thermal balneotherapy: a study in healthy subjects.

    Science.gov (United States)

    Baroni, S; Marazziti, D; Consoli, G; Picchetti, M; Catena-Dell'Osso, M; Galassi, A

    2012-05-01

    Although the beneficial effects of balneotherapy have been recognized since a long time, a few information is available on the biological mechanisms underlying them and the subjective feelings of increased well-being and mood. The links between the serotonin (5-HT) system and mood prompted us to investigate the 5-HT platelet transporter (SERT), which is considered a reliable, peripheral marker of the same structure present in presynaptic neurons, in 30 healthy volunteers before (t0) and 30 minutes after (t1) thermal balneotherapy with ozonized water, as compared with a similar group who underwent a bath in non-mineral water. MATERIALS AN METHODS: The SERT was evaluated by means of the specific binding of 3H-paroxetine (3H-Par) to platelet membranes. Equilibrium-saturation binding data, the maximal binding capacity (Bmax) and the dissociation constant (Kd), were obtained by means of the Scatchard analysis. The results showed that, while Bmax values did not change in both groups, the Kd values decreased significantly at t1 only in those subjects who bathed in ozonized water. The results of this study, while showing a decrease of the dissociation constant (Kd) which is the inverse of affinity constant, of 3H-Par binding to SERT in all subjects after balneotherapy and not in those bathing in normal water, suggest that SERT modifications may be related to a specific effect of ozonized water and, perhaps, also to the increased sense of well-being.

  10. Serotonin transporter genotype modulates social reward and punishment in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Karli K Watson

    Full Text Available Serotonin signaling influences social behavior in both human and nonhuman primates. In humans, variation upstream of the promoter region of the serotonin transporter gene (5-HTTLPR has recently been shown to influence both behavioral measures of social anxiety and amygdala response to social threats. Here we show that length polymorphisms in 5-HTTLPR predict social reward and punishment in rhesus macaques, a species in which 5-HTTLPR variation is analogous to that of humans.In contrast to monkeys with two copies of the long allele (L/L, monkeys with one copy of the short allele of this gene (S/L spent less time gazing at face than non-face images, less time looking in the eye region of faces, and had larger pupil diameters when gazing at photos of a high versus low status male macaques. Moreover, in a novel primed gambling task, presentation of photos of high status male macaques promoted risk-aversion in S/L monkeys but promoted risk-seeking in L/L monkeys. Finally, as measured by a "pay-per-view" task, S/L monkeys required juice payment to view photos of high status males, whereas L/L monkeys sacrificed fluid to see the same photos.These data indicate that genetic variation in serotonin function contributes to social reward and punishment in rhesus macaques, and thus shapes social behavior in humans and rhesus macaques alike.

  11. Transportation

    International Nuclear Information System (INIS)

    Anon.

    1998-01-01

    Here is the decree of the thirtieth of July 1998 relative to road transportation, to trade and brokerage of wastes. It requires to firms which carry out a road transportation as well as to traders and to brokers of wastes to declare their operations to the prefect. The declaration has to be renewed every five years. (O.M.)

  12. Phosphate transport in pig proximal small intestines during postnatal development: lack of modulation by calcitriol.

    Science.gov (United States)

    Schröder, B; Hattenhauer, O; Breves, G

    1998-04-01

    the apical Pi uptake represents the major rate-limiting step of the overall transepithelial Pi transport. At weaning, Na+/Pi transport across the intestinal brush-border membrane is clearly stimulated by calcitriol, but no significant effects of age or calcitriol on the Km values (0.5-0.7 mmol/liter) were observed. In conclusion, our findings reveal calcitriol-independent mechanisms for active intestinal Pi absorption during the neonatal and suckling periods. The onset of the classical calcitriol-dependent mechanism for active intestinal Pi absorption does not occur until weaning.

  13. Surface/Interface Carrier-Transport Modulation for Constructing Photon-Alternative Ultraviolet Detectors Based on Self-Bending-Assembled ZnO Nanowires.

    Science.gov (United States)

    Guo, Zhen; Zhou, Lianqun; Tang, Yuguo; Li, Lin; Zhang, Zhiqi; Yang, Hongbo; Ma, Hanbin; Nathan, Arokia; Zhao, Dongxu

    2017-09-13

    Surface/interface charge-carrier generation, diffusion, and recombination/transport modulation are especially important in the construction of photodetectors with high efficiency in the field of nanoscience. In the paper, a kind of ultraviolet (UV) detector is designed based on ZnO nanostructures considering photon-trapping, surface plasmonic resonance (SPR), piezophototronic effects, interface carrier-trapping/transport control, and collection. Through carefully optimized surface/interface carrier-transport modulation, a designed device with detectivity as high as 1.69 × 10 16 /1.71 × 10 16 cm·Hz 1/2 /W irradiating with 380 nm photons under ultralow bias of 0.2 V is realized by alternating nanoparticle/nanowire active layers, respectively, and the designed UV photodetectors show fast and slow recovery processes of 0.27 and 4.52 ms, respectively, which well-satisfy practical needs. Further, it is observed that UV photodetection could be performed within an alternative response by varying correlated key parameters, through efficient surface/interface carrier-transport modulation, spectrally resolved photoresponse of the detector revealing controlled detection in the UV region based on the ZnO nanomaterial, photodetection allowed or limited by varying the active layers, irradiation distance from one of the electrodes, standing states, or electric field. The detailed carrier generation, diffusion, and recombination/transport processes are well illustrated to explain charge-carrier dynamics contributing to the photoresponse behavior.

  14. Intestinal Serotonin Transporter Inhibition by Toll-Like Receptor 2 Activation. A Feedback Modulation.

    Directory of Open Access Journals (Sweden)

    Eva Latorre

    Full Text Available TLR2 is a microbiota recognition receptor that has been described to contribute to intestinal homeostasis and to ameliorate inflammatory intestinal injury. In this context, serotonin (5-HT has shown to be an essential intestinal physiological neuromodulator that is also involved in intestinal inflammatory diseases. Since the interaction between TLR2 activation and the intestinal serotoninergic system remains non-investigated, our main aim was to analyze the effect of TLR2 on intestinal serotonin transporter (SERT activity and expression and the intracellular pathways involved. Caco-2/TC7 cells were used to analyze SERT and TLR2 molecular expression and SERT activity by measuring 5-HT uptake. The results showed that apical TLR2 activation inhibits SERT activity in Caco-2/TC7 cells mainly by reducing SERT protein level either in the plasma membrane, after short-term TLR2 activation or in both the plasma membrane and cell lysate, after long-term activation. cAMP/PKA pathway appears to mediate short-term inhibitory effect of TLR2 on SERT; however, p38 MAPK pathway has been shown to be involved in both short- and long-term TLR2 effect. Reciprocally, 5-HT long-term treatment yielded TLR2 down regulation in Caco-2/TC7 cells. Finally, results from in vivo showed an augmented intestinal SERT expression in mice Tlr2-/-, thus confirming our inhibitory effect of TLR2 on intestinal SERT in vitro. The present work infers that TLR2 may act in intestinal pathophysiology, not only by its inherent innate immune role, but also by regulating the intestinal serotoninergic system.

  15. The endocannabinoid transport inhibitor AM404 differentially modulates recognition memory in rats depending on environmental aversiveness

    Directory of Open Access Journals (Sweden)

    Patrizia eCampolongo

    2012-03-01

    Full Text Available Cannabinoid compounds may influence both emotional and cognitive processes depending on the level of environmental aversiveness at the time of drug administration. However, the mechanisms responsible for these responses remain to be elucidated. The present experiments investigated the effects induced by the endocannabinoid transport inhibitor AM404 (0.5-5 mg/kg, i.p. on bothemotional and cognitive performances of rats tested in a Spatial Open Field task and subjected to different experimental settings, named High Arousal and Low Arousal conditions. The two different experimental conditions influenced emotional reactivity independently of drug administration. Indeed, vehicle-treated rats exposed to the Low Arousal condition spent more time in the centre of the arena than vehicle-treated rats exposed to the High Arousal context. Conversely, the different arousal conditions did not affect the cognitive performances of vehicle-treated animals such as the capability to discriminate a spatial displacement of the objects or an object substitution.AM404 administration did not alter the locomotor activity of the animals exposed to both environmental conditions. Interestingly, AM404 administration increased the emotional reactivity of rats exposed to the High Arousal condition but did not influence emotionality of rats exposed to the Low Arousal condition. Moreover, AM404 administration influenced the cognitive parameters depending on the level of emotional arousal: it impaired the capability of rats exposed to the High Arousal condition to recognize a novel object while it did not induce any impairing effect in rats exposed to the Low Arousal condition.These findings suggest that drugs which enhance the endocannabinoid signalling induce different effects on recognition memory performance depending on the level of emotional arousal induced by the environmental conditions.

  16. A role for accumbal glycine receptors in modulation of dopamine release by the glycine transporter-1 inhibitor Org25935

    Directory of Open Access Journals (Sweden)

    Helga eHöifödt Lidö

    2011-03-01

    Full Text Available AbstractAccumbal glycine modulates basal and ethanol-induced dopamine levels in the nucleus accumbens (nAc as well as voluntary ethanol consumption. Also, systemic administration of the glycine transporter-1 inhibitor Org25935 elevates dopamine levels in nAc, prevents a further ethanol-induced dopamine elevation and robustly and dose-dependently decreases ethanol consumption in rats. Here we investigated whether Org25935 applied locally in nAc modulates dopamine release, and whether accumbal glycine receptors or NMDA receptors are involved in this tentative effect. We also addressed whether Org25935 and ethanol applied locally in nAc interact with dopamine levels, as seen after systemic administration. We used in vivo microdialysis coupled to HPLC-ED in freely moving male Wistar rats to monitor dopamine output in nAc after local perfusion of Org25935 alone, with ethanol, or Org25935-perfusion after pre-treatment with the glycine receptor antagonist strychnine or the NMDA receptor glycine site antagonist L-701.324. Local Org25935 increased extracellular dopamine levels in a subpopulation of rats. Local strychnine, but not systemic L-701.324, antagonized the dopamine-activating effect of Org25935. Ethanol failed to induce a dopamine overflow in the subpopulation responding to Org25935 with a dopamine elevation. The study supports a role for accumbal glycine receptors rather than NMDA receptor signaling in the dopamine-activating effect of Org25935. The results further indicate that the previously reported systemic Org25935-ethanol interaction with regard to accumbal dopamine is localized to the nAc. This adds to the growing evidence for the glycine receptor as an important player in the dopamine reward circuitry and in ethanol’s effects within this system.

  17. Pharmacological Modulation of the Mitochondrial Electron Transport Chain in Paclitaxel-Induced Painful Peripheral Neuropathy.

    Science.gov (United States)

    Griffiths, Lisa A; Flatters, Sarah J L

    2015-10-01

    Paclitaxel is an effective first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Mitochondrial dysfunction and oxidative stress have been implicated in paclitaxel-induced painful neuropathy. Here we show the effects of pharmacological modulation of mitochondrial sites that produce reactive oxygen species using systemic rotenone (complex I inhibitor) or antimycin A (complex III inhibitor) on the maintenance and development of paclitaxel-induced mechanical hypersensitivity in adult male Sprague Dawley rats. The maximally tolerated dose (5 mg/kg) of rotenone inhibited established paclitaxel-induced mechanical hypersensitivity. However, some of these inhibitory effects coincided with decreased motor coordination; 3 mg/kg rotenone also significantly attenuated established paclitaxel-induced mechanical hypersensitivity without any motor impairment. The maximally tolerated dose (.6 mg/kg) of antimycin A reversed established paclitaxel-induced mechanical hypersensitivity without any motor impairment. Seven daily doses of systemic rotenone or antimycin A were given either after paclitaxel administration or before and during paclitaxel administration. Rotenone had no significant effect on the development of paclitaxel-induced mechanical hypersensitivity. However, antimycin A significantly inhibited the development of paclitaxel-induced mechanical hypersensitivity when given before and during paclitaxel administration but had no effect when given after paclitaxel administration. These studies provide further evidence of paclitaxel-evoked mitochondrial dysfunction in vivo, suggesting that complex III activity is instrumental in paclitaxel-induced pain. This study provides further in vivo evidence that mitochondrial dysfunction is a key contributor to the development and maintenance of chemotherapy-induced painful neuropathy. This work also indicates that selective modulation of the electron transport chain can induce antinociceptive

  18. Glycogen Synthase Kinase-3 Modulates Hyperosmotic-Induced Urea Transporter A1 Relocation in the Inner Medullary Collecting Duct Cells.

    Science.gov (United States)

    Li, Yong-Xia; Huang, Yun; Liu, Song; Mao, Yan; Yuan, Cheng-Yan; Yang, Xiao; Yao, Li-Jun

    2016-01-01

    Glycogen synthase kinase 3 (GSK3) regulates urine concentration by mediating the vasopressin-induced aquaporin 2 expression and water permeability, although it is unknown whether GSK3 also mediates the accumulation of the urea transporter A1 (UT-A1). The aim of this study is to investigate the effect of GSK3 on UT-A1 distribution. Mouse inner medullary collecting duct 3 cells were transfected with UT-A1-GFP construct. The stable transfected cells were cultured under hypertonic conditions, treated with GSK3 inhibitor lithium chloride, GSK3 activator, lysosome or proteasome inhibitor. The expression levels of UT-A1, GSK3, and phospho-GSK3 were analyzed using western blot. The interaction between UT-A1 and the Golgi apparatus was examined using confocal immunofluorescence microscope. The UT-A1 trafficking was examined using the biotinylation of surface membranes. UT-A1 dissociated away from the Golgi apparatus and translocated to the plasma membrane under hypertonic-NaCl and NaCl plus urea stimulation. This movement was accompanied by the increased phosphorylation of GSK3 and its localization on the cellular membrane. Moreover, these results were duplicated by treating the cells with the GSK3 inhibitor, and by contrast, were partially reversed by the GSK3 activator. Treating cells with a lysosome or proteasome inhibitor failed to attenuate the effects of hypertonic stimulus, indicating that the loss of UT-A1 from the Golgi was not due to degradation. Our results suggest that GSK3 may in part modulate the hypertonic-induced intracellular UT-A1 redistribution and its accumulation on the plasma membrane, which may constitute another mechanism by which GSK3 modulates urine concentration. © 2016 S. Karger AG, Basel.

  19. Localisation of selected Ca2+-transport systems in rat's heart and kidney and their modulation by stress

    International Nuclear Information System (INIS)

    Zacikova, L.

    2000-01-01

    This thesis deals with the identification of selected calcium transport systems and their modulation by immobilization stress in rat heart and kidney. In our experiments we used normotensive (Sprague-Dawley, Wistar-Kyoto) and hypertensive (SHR) strains. We compared mRNA levels, protein expression and activity of the Na + /Ca 2+ exchanger from hearts of control animals, animals subjected to a single (once) or repeated (seven times) immobilization stress and from animals treated continually with cortisol. We have observed that immobilization stress increased both, gene expression and protein message of the Na + /Ca 2 + exchanger in rat cardiac left, but not right ventricle. This effect is not mediated through the glucocorticoid responsive element. We have found that cortisol decreased activity of the N a +/Ca 2+ exchanger without changing expression and protein amount of this transport system. IP3 receptor of type I and 2 was detected on mRNA levels in rat cardiac atria. Very small amounts of these receptors were observed in rat cardiac ventricles. Since it was difficult to detect these amounts in ventricles, we used 'seminested' PCR to verify expression of IP 3 R1 and 2 in cardiac ventricles. The highest levels of IP 3 R1 and 2 were expressed in left atria. Immobilization stress significantly increased mRNA IP 3 R1 and 2 in rat cardiac atria. We observed both, mRNA and type 1 IP 3 receptor's protein in renal medulla, but not in renal cortex. We have found that this receptor was approximately twice as abundant in normotensive as in genetically hypertensive rat kidney. Immobilization stress significantly down-regulated IP 3 R1 in renal medulla, but not in renal cortex. To investigate the role of NAADP in signaling we measured 45 Ca 2+ release from rat cardiac microsomes. We examined concentration and time dependence of 45 Ca 2+ release from rat cardiac microsomes. All these results could contribute to the understanding of Ca 2+ modulation in cardiac and kidney under

  20. Enigma interacts with adaptor protein with PH and SH2 domains to control insulin-induced actin cytoskeleton remodeling and glucose transporter 4 translocation

    DEFF Research Database (Denmark)

    Barres, Romain; Grémeaux, Thierry; Gual, Philippe

    2006-01-01

    a critical role in actin cytoskeleton organization in fibroblastic cells. Because actin rearrangement is important for insulin-induced glucose transporter 4 (Glut 4) translocation, we studied the potential involvement of Enigma in insulin-induced glucose transport in 3T3-L1 adipocytes. Enigma m...

  1. Adaptor protein containing PH domain, PTB domain and leucine zipper (APPL1) regulates the protein level of EGFR by modulating its trafficking

    International Nuclear Information System (INIS)

    Lee, Jae-Rin; Hahn, Hwa-Sun; Kim, Young-Hoon; Nguyen, Hong-Hoa; Yang, Jun-Mo; Kang, Jong-Sun; Hahn, Myong-Joon

    2011-01-01

    Highlights: ► APPL1 regulates the protein level of EGFR in response to EGF stimulation. ► Depletion of APPL1 accelerates the movement of EGF/EGFR from the cell surface to the perinuclear region in response to EGF. ► Knockdown of APPL1 enhances the activity of Rab5. -- Abstract: The EGFR-mediated signaling pathway regulates multiple biological processes such as cell proliferation, survival and differentiation. Previously APPL1 (adaptor protein containing PH domain, PTB domain and leucine zipper 1) has been reported to function as a downstream effector of EGF-initiated signaling. Here we demonstrate that APPL1 regulates EGFR protein levels in response to EGF stimulation. Overexpression of APPL1 enhances EGFR stabilization while APPL1 depletion by siRNA reduces EGFR protein levels. APPL1 depletion accelerates EGFR internalization and movement of EGF/EGFR from cell surface to the perinuclear region in response to EGF treatment. Conversely, overexpression of APPL1 decelerates EGFR internalization and translocation of EGF/EGFR to the perinuclear region. Furthermore, APPL1 depletion enhances the activity of Rab5 which is involved in internalization and trafficking of EGFR and inhibition of Rab5 in APPL1-depleted cells restored EGFR levels. Consistently, APPL1 depletion reduced activation of Akt, the downstream signaling effector of EGFR and this is restored by inhibition of Rab5. These findings suggest that APPL1 is required for EGFR signaling by regulation of EGFR stabilities through inhibition of Rab5.

  2. Transportation

    National Research Council Canada - National Science Library

    Allshouse, Michael; Armstrong, Frederick Henry; Burns, Stephen; Courts, Michael; Denn, Douglas; Fortunato, Paul; Gettings, Daniel; Hansen, David; Hoffman, D. W; Jones, Robert

    2007-01-01

    .... The ability of the global transportation industry to rapidly move passengers and products from one corner of the globe to another continues to amaze even those wise to the dynamics of such operations...

  3. Adrenergic pathways in dopamine modulation of K+ transport in cortex slices after low dose X-Rays

    International Nuclear Information System (INIS)

    Kulikova, I.A.; Dvoretsky, A.I.

    1997-01-01

    Using the method of surviving brain cortex slices it has been shown that prolonged whole body acute or chronic 25 cGy X-irradiation (1 cGy/day at dose rate of 2.22 mGy/min) essentially modified dopamine (DA) modulating influence upon Na, K-pump in nervous tissue. Obtained results pointed to that normally DA had the defined biphasic effect upon active K + transport with lower level activation (by 24.0 %) and higher level inhibition (by 42.1 %). The patterns of the Na,K-pump reaction to DA was not changed after irradiation, but percentage of the total DA suppression was increased by 15.1 % in average after single X-ray exposure and by 34.5 % after chronic one. The decisive role of β-adrenergic mechanisms in realization of postirradiation interaction between systems of catecholamine and active K + transfer across neuronal membrane has been determined. Experimental data obtained with the use of 10 μM phentolamine and 10 μM propranolol, respectively α- and β-adrenergic antagonists, supported that metabolic DA effect was mediated via α-AR normally, and via β-AR after low dose-rate irradiation. (authors)

  4. The serotonin transporter polymorphism (5-HTTLPR) and cortisol stress responsiveness: preliminary evidence for a modulating role for sleep quality.

    Science.gov (United States)

    van Dalfsen, Jens H; Markus, C Rob

    2018-05-23

    The short (S) allele of a functional polymorphism (5-HTTLPR) within the promoter region of the serotonin transporter gene (SLC6A4) is found to predispose the risk for stress-related affective disorders relative to the long (L) allele. Evidence suggests that elevated stress reactivity of the hypothalamic-pituitary-adrenal (HPA) axis might underlie this association although there is little understanding about the origin of inconsistent findings. Since inadequate sleep is commonly known to promote HPA stress reactivity, it might well play an important modulating role. The present study tested this hypothesis by investigating whether sleep quality moderates the relationship between 5-HTTLPR and cortisol stress responsiveness. From a large 5-HTTLPR database (n = 771), a sample of healthy male and female participants homozygous for either the 5-HTTLPR S-allele (n = 25) or L-allele (n = 25) were assessed for sleep quality and salivary cortisol secretion during acute laboratory stress. Diminished sleep quality was found to exclusively potentiate cortisol stress reactivity in the homozygous L-allele genotype. Accounting for this 5-HTTLPR-dependent influence enhanced the predictive value of 5-HTTLPR on cortisol stress responsiveness, revealing greater HPA reactivity in S-allele relative to L-allele carriers. Current findings suggest that variations in sleep quality may serve as a confounding factor in the search for genetic differences in stress sensitivity and related affective disorders.

  5. Development of a fission product transport module predicting the behavior of radiological materials during sever accidents in a nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hyung Seok; Rhee, Bo Wook; Kim, Dong Ha [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-09-15

    Korea Atomic Energy Research Institute is developing a fission product transport module for predicting the behavior of radioactive materials in the primary cooling system of a nuclear power plant as a separate module, which will be connected to a severe accident analysis code, Core Meltdown Progression Accident Simulation Software (COMPASS). This fission product transport (COMPASS-FP) module consists of a fission product release model, an aerosol generation model, and an aerosol transport model. In the fission product release model there are three submodels based on empirical correlations, and they are used to simulate the fission product gases release from the reactor core. In the aerosol generation model, the mass conservation law and Raoult's law are applied to the mixture of vapors and droplets of the fission products in a specified control volume to find the generation of the aerosol droplet. In the aerosol transport model, empirical correlations available from the open literature are used to simulate the aerosol removal processes owing to the gravitational settling, inertia impaction, diffusiophoresis, and thermophoresis. The COMPASS-FP module was validated against Aerosol Behavior Code Validation and Evaluation (ABCOVE-5) test performed by Hanford Engineering Development Laboratory for comparing the prediction and test data. The comparison results assuming a non-spherical aerosol shape for the suspended aerosol mass concentration showed a good agreement with an error range of about ±6%. It was found that the COMPASS-FP module produced the reasonable results of the fission product gases release, the aerosol generation, and the gravitational settling in the aerosol removal processes for ABCOVE-5. However, more validation for other aerosol removal models needs to be performed.

  6. Development of a Grid-Independent Geos-Chem Chemical Transport Model (v9-02) as an Atmospheric Chemistry Module for Earth System Models

    Science.gov (United States)

    Long, M. S.; Yantosca, R.; Nielsen, J. E; Keller, C. A.; Da Silva, A.; Sulprizio, M. P.; Pawson, S.; Jacob, D. J.

    2015-01-01

    The GEOS-Chem global chemical transport model (CTM), used by a large atmospheric chemistry research community, has been re-engineered to also serve as an atmospheric chemistry module for Earth system models (ESMs). This was done using an Earth System Modeling Framework (ESMF) interface that operates independently of the GEOSChem scientific code, permitting the exact same GEOSChem code to be used as an ESM module or as a standalone CTM. In this manner, the continual stream of updates contributed by the CTM user community is automatically passed on to the ESM module, which remains state of science and referenced to the latest version of the standard GEOS-Chem CTM. A major step in this re-engineering was to make GEOS-Chem grid independent, i.e., capable of using any geophysical grid specified at run time. GEOS-Chem data sockets were also created for communication between modules and with external ESM code. The grid-independent, ESMF-compatible GEOS-Chem is now the standard version of the GEOS-Chem CTM. It has been implemented as an atmospheric chemistry module into the NASA GEOS- 5 ESM. The coupled GEOS-5-GEOS-Chem system was tested for scalability and performance with a tropospheric oxidant-aerosol simulation (120 coupled species, 66 transported tracers) using 48-240 cores and message-passing interface (MPI) distributed-memory parallelization. Numerical experiments demonstrate that the GEOS-Chem chemistry module scales efficiently for the number of cores tested, with no degradation as the number of cores increases. Although inclusion of atmospheric chemistry in ESMs is computationally expensive, the excellent scalability of the chemistry module means that the relative cost goes down with increasing number of cores in a massively parallel environment.

  7. Development and evaluation of the microbial fate and transport module for the Agricultural Policy/Environmental eXtender (APEX) model

    Science.gov (United States)

    Hong, Eun-Mi; Park, Yongeun; Muirhead, Richard; Pachepsky, Yakov

    2017-04-01

    Pathogenic microorganisms in recreational and irrigation waters remain the subject of concern. Water quality models are used to estimate microbial quality of water sources, to evaluate microbial contamination-related risks, to guide the microbial water quality monitoring, and to evaluate the effect of agricultural management on the microbial water quality. The Agricultural Policy/Environmental eXtender (APEX) is the watershed-scale water quality model that includes highly detailed representation of agricultural management. The APEX currently does not have microbial fate and transport simulation capabilities. The objective of this work was to develop the first APEX microbial fate and transport module that could use the APEX conceptual model of manure removal together with recently introduced conceptualizations of the in-stream microbial fate and transport. The module utilizes manure erosion rates found in the APEX. The total number of removed bacteria was set to the concentrations of bacteria in soil-manure mixing layer and eroded manure amount. Bacteria survival in soil-manure mixing layer was simulated with the two-stage survival model. Individual survival patterns were simulated for each manure application date. Simulated in-stream microbial fate and transport processes included the reach-scale passive release of bacteria with resuspended bottom sediment during high flow events, the transport of bacteria from bottom sediment due to the hyporheic exchange during low flow periods, the deposition with settling sediment, and the two-stage survival. Default parameter values were available from recently published databases. The APEX model with the newly developed microbial fate and transport module was applied to simulate seven years of monitoring data for the Toenepi watershed in New Zealand. The stream network of the watershed ran through grazing lands with the daily bovine waste deposition. Based on calibration and testing results, the APEX with the microbe module

  8. Modulation of bilirubin neurotoxicity by the Abcb1 transporter in the Ugt1-/- lethal mouse model of neonatal hyperbilirubinemia.

    Science.gov (United States)

    Bockor, Luka; Bortolussi, Giulia; Vodret, Simone; Iaconcig, Alessandra; Jašprová, Jana; Zelenka, Jaroslav; Vitek, Libor; Tiribelli, Claudio; Muro, Andrés F

    2017-01-01

    Moderate neonatal jaundice is the most common clinical condition during newborn life. However, a combination of factors may result in acute hyperbilirubinemia, placing infants at risk of developing bilirubin encephalopathy and death by kernicterus. While most risk factors are known, the mechanisms acting to reduce susceptibility to bilirubin neurotoxicity remain unclear. The presence of modifier genes modulating the risk of developing bilirubin-induced brain damage is increasingly being recognised. The Abcb1 and Abcc1 members of the ABC family of transporters have been suggested to have an active role in exporting unconjugated bilirubin from the central nervous system into plasma. However, their role in reducing the risk of developing neurological damage and death during neonatal development is still unknown.To this end, we mated Abcb1a/b-/- and Abcc1-/- strains with Ugt1-/- mice, which develop severe neonatal hyperbilirubinemia. While about 60% of Ugt1-/- mice survived after temporary phototherapy, all Abcb1a/b-/-/Ugt1-/- mice died before postnatal day 21, showing higher cerebellar levels of unconjugated bilirubin. Interestingly, Abcc1 role appeared to be less important.In the cerebellum of Ugt1-/- mice, hyperbilirubinemia induced the expression of Car and Pxr nuclear receptors, known regulators of genes involved in the genotoxic response.We demonstrated a critical role of Abcb1 in protecting the cerebellum from bilirubin toxicity during neonatal development, the most clinically relevant phase for human babies, providing further understanding of the mechanisms regulating bilirubin neurotoxicity in vivo. Pharmacological treatments aimed to increase Abcb1 and Abcc1 expression, could represent a therapeutic option to reduce the risk of bilirubin neurotoxicity. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Polarization-multiplexed rate-adaptive non-binary-quasi-cyclic-LDPC-coded multilevel modulation with coherent detection for optical transport networks.

    Science.gov (United States)

    Arabaci, Murat; Djordjevic, Ivan B; Saunders, Ross; Marcoccia, Roberto M

    2010-02-01

    In order to achieve high-speed transmission over optical transport networks (OTNs) and maximize its throughput, we propose using a rate-adaptive polarization-multiplexed coded multilevel modulation with coherent detection based on component non-binary quasi-cyclic (QC) LDPC codes. Compared to prior-art bit-interleaved LDPC-coded modulation (BI-LDPC-CM) scheme, the proposed non-binary LDPC-coded modulation (NB-LDPC-CM) scheme not only reduces latency due to symbol- instead of bit-level processing but also provides either impressive reduction in computational complexity or striking improvements in coding gain depending on the constellation size. As the paper presents, compared to its prior-art binary counterpart, the proposed NB-LDPC-CM scheme addresses the needs of future OTNs, which are achieving the target BER performance and providing maximum possible throughput both over the entire lifetime of the OTN, better.

  10. Transportation

    Science.gov (United States)

    2007-01-01

    Faculty ii INDUSTRY TRAVEL Domestic Assistant Deputy Under Secretary of Defense (Transportation Policy), Washington, DC Department of...developed between the railroad and trucking industries. Railroads: Today’s seven Class I freight railroad systems move 42% of the nation’s intercity ...has been successfully employed in London to reduce congestion and observed by this industry study during its travels . It is currently being

  11. Development and evaluation of the bacterial fate and transport module for the Agricultural Policy/Environmental eXtender (APEX) model.

    Science.gov (United States)

    Hong, Eun-Mi; Park, Yongeun; Muirhead, Richard; Jeong, Jaehak; Pachepsky, Yakov A

    2018-02-15

    The Agricultural Policy/Environmental eXtender (APEX) is a watershed-scale water quality model that includes detailed representation of agricultural management. The objective of this work was to develop a process-based model for simulating the fate and transport of manure-borne bacteria on land and in streams with the APEX model. The bacteria model utilizes manure erosion rates to estimate the amount of edge-of-field bacteria export. Bacteria survival in manure is simulated as a two-stage process separately for each manure application event. In-stream microbial fate and transport processes include bacteria release from streambeds due to sediment resuspension during high flow events, active release from the streambed sediment during low flow periods, bacteria settling with sediment, and survival. Default parameter values were selected from published databases and evaluated based on field observations. The APEX model with the newly developed microbial fate and transport module was applied to simulate fate and transport of the fecal indicator bacterium Escherichia coli in the Toenepi watershed, New Zealand that was monitored for seven years. The stream network of the watershed ran through grazing lands with daily bovine waste deposition. Results show that the APEX with the bacteria module reproduced well the monitored pattern of E. coli concentrations at the watershed outlet. The APEX with the microbial fate and transport module will be utilized for predicting microbial quality of water as affected by various agricultural practices, evaluating monitoring protocols, and supporting the selection of management practices based on regulations that rely on fecal indicator bacteria concentrations. Published by Elsevier B.V.

  12. The pH Stability of Foot-and-Mouth Disease Virus Particles Is Modulated by Residues Located at the Pentameric Interface and in the N Terminus of VP1.

    Science.gov (United States)

    Caridi, Flavia; Vázquez-Calvo, Angela; Sobrino, Francisco; Martín-Acebes, Miguel A

    2015-05-01

    The picornavirus foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects important livestock species. The FMDV capsid is highly acid labile, and viral particles lose infectivity due to their disassembly at pH values slightly below neutrality. This acid sensitivity is related to the mechanism of viral uncoating and genome penetration from endosomes. In this study, we have analyzed the molecular basis of FMDV acid-induced disassembly by isolating and characterizing a panel of novel FMDV mutants differing in acid sensitivity. Amino acid replacements altering virion stability were preferentially distributed in two different regions of the capsid: the N terminus of VP1 and the pentameric interface. Even more, the acid labile phenotype induced by a mutation located at the pentameric interface in VP3 could be compensated by introduction of an amino acid substitution in the N terminus of VP1. These results indicate that the acid sensitivity of FMDV can be considered a multifactorial trait and that virion stability is the fine-tuned product of the interaction between residues from different capsid proteins, in particular those located within the N terminus of VP1 or close to the pentameric interface. The viral capsid protects the viral genome from environmental factors and contributes to virus dissemination and infection. Thus, understanding of the molecular mechanisms that modulate capsid stability is of interest for the basic knowledge of the biology of viruses and as a tool to improve the stability of conventional vaccines based on inactivated virions or empty capsids. Using foot-and-mouth disease virus (FMDV), which displays a capsid with extreme acid sensitivity, we have performed a genetic study to identify the molecular determinants involved in capsid stability. A panel of FMDV mutants with differential sensitivity to acidic pH was generated and characterized, and the results showed that two different regions of FMDV

  13. Glucose Modulation Induces Lysosome Formation and Increases Lysosomotropic Drug Sequestration via the P-Glycoprotein Drug Transporter.

    Science.gov (United States)

    Seebacher, Nicole A; Lane, Darius J R; Jansson, Patric J; Richardson, Des R

    2016-02-19

    Pgp is functional on the plasma membrane and lysosomal membrane. Lysosomal-Pgp can pump substrates into the organelle, thereby trapping certain chemotherapeutics (e.g. doxorubicin; DOX). This mechanism serves as a "safe house" to protect cells against cytotoxic drugs. Interestingly, in contrast to DOX, lysosomal sequestration of the novel anti-tumor agent and P-glycoprotein (Pgp) substrate, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), induces lysosomal membrane permeabilization. This mechanism of lysosomal-Pgp utilization enhances cytotoxicity to multidrug-resistant cells. Consequently, Dp44mT has greater anti-tumor activity in drug-resistant relative to non-Pgp-expressing tumors. Interestingly, stressors in the tumor microenvironment trigger endocytosis for cell signaling to assist cell survival. Hence, this investigation examined how glucose variation-induced stress regulated early endosome and lysosome formation via endocytosis of the plasma membrane. Furthermore, the impact of glucose variation-induced stress on resistance to DOX was compared with Dp44mT and its structurally related analogue, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC). These studies showed that glucose variation-induced stress-stimulated formation of early endosomes and lysosomes. In fact, through the process of fluid-phase endocytosis, Pgp was redistributed from the plasma membrane to the lysosomal membrane via early endosome formation. This lysosomal-Pgp actively transported the Pgp substrate, DOX, into the lysosome where it became trapped as a result of protonation at pH 5. Due to increased lysosomal DOX trapping, Pgp-expressing cells became more resistant to DOX. In contrast, cytotoxicity of Dp44mT and DpC was potentiated due to more lysosomes containing functional Pgp under glucose-induced stress. These thiosemicarbazones increased lysosomal membrane permeabilization and cell death. This mechanism has critical implications for drug-targeting in

  14. Differential gene expression in tomato fruit and Colletotrichum gloeosporioides during colonization of the RNAi-SlPH tomato line with reduced fruit acidity and higher pH.

    Science.gov (United States)

    Barad, Shiri; Sela, Noa; Dubey, Amit K; Kumar, Dilip; Luria, Neta; Ment, Dana; Cohen, Shahar; Schaffer, Arthur A; Prusky, Dov

    2017-08-04

    The destructive phytopathogen Colletotrichum gloeosporioides causes anthracnose disease in fruit. During host colonization, it secretes ammonia, which modulates environmental pH and regulates gene expression, contributing to pathogenicity. However, the effect of host pH environment on pathogen colonization has never been evaluated. Development of an isogenic tomato line with reduced expression of the gene for acidity, SlPH (Solyc10g074790.1.1), enabled this analysis. Total RNA from C. gloeosporioides colonizing wild-type (WT) and RNAi-SlPH tomato lines was sequenced and gene-expression patterns were compared. C. gloeosporioides inoculation of the RNAi-SlPH line with pH 5.96 compared to the WT line with pH 4.2 showed 30% higher colonization and reduced ammonia accumulation. Large-scale comparative transcriptome analysis of the colonized RNAi-SlPH and WT lines revealed their different mechanisms of colonization-pattern activation: whereas the WT tomato upregulated 13-LOX (lipoxygenase), jasmonic acid and glutamate biosynthesis pathways, it downregulated processes related to chlorogenic acid biosynthesis II, phenylpropanoid biosynthesis and hydroxycinnamic acid tyramine amide biosynthesis; the RNAi-SlPH line upregulated UDP-D-galacturonate biosynthesis I and free phenylpropanoid acid biosynthesis, but mainly downregulated pathways related to sugar metabolism, such as the glyoxylate cycle and L-arabinose degradation II. Comparison of C. gloeosporioides gene expression during colonization of the WT and RNAi-SlPH lines showed that the fungus upregulates ammonia and nitrogen transport and the gamma-aminobutyric acid metabolic process during colonization of the WT, while on the RNAi-SlPH tomato, it mainly upregulates the nitrate metabolic process. Modulation of tomato acidity and pH had significant phenotypic effects on C. gloeosporioides development. The fungus showed increased colonization on the neutral RNAi-SlPH fruit, and limited colonization on the WT acidic fruit

  15. Activity Development for Intersection Operations The National Transportation Curriculum Project : Developing Activity-Based Learning Modules for the Introductory Transportation Engineering Course

    Science.gov (United States)

    2012-05-01

    The goal of this work was to develop activity-based learning materials for the introductory transportation engineering course : with the purpose of increasing student understanding and concept retention. These materials were to cover intersection : o...

  16. The non-Newtonian heat and mass transport of He 2 in porous media used for vapor-liquid phase separation. Ph.D. Thesis

    Science.gov (United States)

    Yuan, S. W. K.

    1985-01-01

    This investigation of vapor-liquid phase separation (VLPS) of He 2 is related to long-term storage of cryogenic liquid. The VLPS system utilizes porous plugs in order to generate thermomechanical (thermo-osmotic) force which in turn prevents liquid from flowing out of the cryo-vessel (e.g., Infrared Astronomical Satellite). An apparatus was built and VLPS data were collected for a 2 and a 10 micrometer sintered stainless steel plug and a 5 to 15 micrometer sintered bronze plug. The VLPS data obtained at high temperature were in the nonlinear turbulent regime. At low temperature, the Stokes regime was approached. A turbulent flow model was developed, which provides a phenomenological description of the VLPS data. According to the model, most of the phase separation data are in the turbulent regime. The model is based on concepts of the Gorter-Mellink transport involving the mutual friction known from the zero net mass flow (ZNMF) studies. The latter had to be modified to obtain agreement with the present experimental VLPS evidence. In contrast to the well-known ZNMF mode, the VLPS results require a geometry dependent constant (Gorter-Mellink constant). A theoretical interpretation of the phenomenological equation for the VLPS data obtained, is based on modelling of the dynamics of quantized vortices proposed by Vinen. In extending Vinen's model to the VLPS transport of He 2 in porous media, a correlation between the K*(GM) and K(p) was obtained which permits an interpretation of the present findings. As K(p) is crucial, various methods were introduced to measure the permeability of the porous media at low temperatures. Good agreement was found between the room temperature and the low temperature K(p)-value of the plugs.

  17. N-MYC DOWN-REGULATED-LIKE Proteins Regulate Meristem Initiation by Modulating Auxin Transport and MAX2 Expression

    OpenAIRE

    Mudgil, Yashwanti; Ghawana, Sanjay; Jones, Alan M.

    2013-01-01

    Background N-MYC DOWN-REGULATED-LIKE (NDL) proteins interact with the G? subunit (AGB1) of the heterotrimeric G protein complex and play an important role in AGB1-dependent regulation of lateral root formation by affecting root auxin transport, auxin gradients and the steady-state levels of mRNA encoding the PIN-FORMED 2 and AUXIN 1 auxin transport facilitators. Auxin transport in aerial tissue follows different paths and utilizes different transporters than in roots; therefore, in the presen...

  18. Nitric oxide modulates sodium vitamin C transporter 2 (SVCT-2) protein expression via protein kinase G (PKG) and nuclear factor-κB (NF-κB).

    Science.gov (United States)

    Portugal, Camila Cabral; da Encarnação, Thaísa Godinho; Socodato, Renato; Moreira, Sarah Rodrigues; Brudzewsky, Dan; Ambrósio, António Francisco; Paes-de-Carvalho, Roberto

    2012-02-03

    Ascorbate is an important antioxidant, which also displays important functions in neuronal tissues, including the retina. The retina is responsible for the initial steps of visual processing, which is further refined in cerebral high-order centers. The retina is also a prototypical model for studying physiologic aspects of cells that comprise the nervous system. Of major importance also is the cellular messenger nitric oxide (NO). Previous studies have demonstrated the significance of NO for both survival and proliferation of cultured embryonic retinal cells. Cultured retinal cells express a high-affinity ascorbate transporter, and the release of ascorbate is delicately regulated by ionotropic glutamate receptors. Therefore, we proposed whether there is interplay between the ascorbate transport system and NO signaling pathway in retinal cells. Here we show compelling evidence that ascorbate uptake is tightly controlled by NO and its downstream signaling pathway in culture. NO also modulates the expression of SVCT-2, an effect mediated by cGMP and PKG. Kinetic studies suggest that NO increases the transport capacity for ascorbate, but not the affinity of SVCT-2 for its substrate. Interestingly, NO utilizes the NF-κB pathway, in a PKG-dependent manner, to modulate both SVCT-2 expression and ascorbate uptake. These results demonstrate that NO exerts a fine-tuned control of the availability of ascorbate to cultured retinal cells and strongly reinforces ascorbate as an important bioactive molecule in neuronal tissues.

  19. Dynamical heat transport amplification in a far-field thermal transistor of VO{sub 2} excited with a laser of modulated intensity

    Energy Technology Data Exchange (ETDEWEB)

    Ordonez-Miranda, Jose, E-mail: jose.ordonez@cnrs.pprime.fr; Ezzahri, Younès; Drevillon, Jérémie; Joulain, Karl [Institut Pprime, CNRS, Université de Poitiers, ISAE-ENSMA, F-86962 Futuroscope Chasseneuil (France)

    2016-05-28

    Far-field radiative heat transport in a thermal transistor made up of a vanadium dioxide base excited with a laser of modulated intensity is analytically studied and optimized. This is done by solving the equation of energy conservation for the steady-state and modulated components of the temperature and heat fluxes that the base exchanges with the collector and emitter. The thermal bistability of VO{sub 2} is used to find an explicit condition on the laser intensity required to maximize these heat fluxes to values higher than the incident flux. For a 1 μm-thick base heated with a modulation frequency of 0.5 Hz, it is shown that both the DC and AC components of the heat fluxes are about 4 times the laser intensity, while the AC temperature remains an order of magnitude smaller than the DC one at around 343 K. Higher AC heat fluxes are obtained for thinner bases and/or lower frequencies. Furthermore, we find that out of the bistability temperatures associated with the dielectric-to-metal and metal-to-dielectric transitions of VO{sub 2}, the amplification of the collector-to-base and base-to-emitter heat fluxes is still possible, but at modulation frequencies lower than 0.1 Hz.

  20. PhEDEx Data Service

    International Nuclear Information System (INIS)

    Egeland, Ricky; Wildish, Tony; Huang, Chih-Hao

    2010-01-01

    The PhEDEx Data Service provides access to information from the central PhEDEx database, as well as certificate-authenticated managerial operations such as requesting the transfer or deletion of data. The Data Service is integrated with the 'SiteDB' service for fine-grained access control, providing a safe and secure environment for operations. A plug-in architecture allows server-side modules to be developed rapidly and easily by anyone familiar with the schema, and can automatically return the data in a variety of formats for use by different client technologies. Using HTTP access via the Data Service instead of direct database connections makes it possible to build monitoring web-pages with complex drill-down operations, suitable for debugging or presentation from many aspects. This will form the basis of the new PhEDEx website in the near future, as well as providing access to PhEDEx information and certificate-authenticated services for other CMS dataflow and workflow management tools such as CRAB, WMCore, DBS and the dashboard. A PhEDEx command-line client tool provides one-stop access to all the functions of the PhEDEx Data Service interactively, for use in simple scripts that do not access the service directly. The client tool provides certificate-authenticated access to managerial functions, so all the functions of the PhEDEx Data Service are available to it. The tool can be expanded by plug-ins which can combine or extend the client-side manipulation of data from the Data Service, providing a powerful environment for manipulating data within PhEDEx.

  1. Reactive solute transport in acidic streams

    Science.gov (United States)

    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.

  2. Design, analysis, and control of a large transport aircraft utilizing selective engine thrust as a backup system for the primary flight control. Ph.D. Thesis

    Science.gov (United States)

    Gerren, Donna S.

    1995-01-01

    A study has been conducted to determine the capability to control a very large transport airplane with engine thrust. This study consisted of the design of an 800-passenger airplane with a range of 5000 nautical miles design and evaluation of a flight control system, and design and piloted simulation evaluation of a thrust-only backup flight control system. Location of the four wing-mounted engines was varied to optimize the propulsive control capability, and the time constant of the engine response was studied. The goal was to provide level 1 flying qualities. The engine location and engine time constant did not have a large effect on the control capability. The airplane design did meet level 1 flying qualities based on frequencies, damping ratios, and time constants in the longitudinal and lateral-directional modes. Project pilots consistently rated the flying qualities as either level 1 or level 2 based on Cooper-Harper ratings. However, because of the limited control forces and moments, the airplane design fell short of meeting the time required to achieve a 30 deg bank and the time required to respond a control input.

  3. Ph3CCOOSnPh3.Ph3PO AND Ph3CCOOSnPh3.Ph3AsO: SYNTHESIS AND INFRARED STUDY

    Directory of Open Access Journals (Sweden)

    ABDOU MBAYE

    2014-08-01

    Full Text Available The mixture of ethanolic solutions of Ph3CCOOSnPh3 and Ph3PO or Ph3AsO gives Ph3CCOOSnPh3.Ph3PO and Ph3CCOOSnPh3.Ph3AsO adducts which have been characterized by infrared spectroscopy. A discrete structure is suggested for both, the environment around the tin centre being trigonal bipyramidal, the triphenylacetate anion behaving as a mondentate ligand.

  4. Brain-derived neurotrophic factor (BDNF) enhances GABA transport by modulating the trafficking of GABA transporter-1 (GAT-1) from the plasma membrane of rat cortical astrocytes

    DEFF Research Database (Denmark)

    Vaz, Sandra H; Jørgensen, Trine Nygaard; Cristóvão-Ferreira, Sofia

    2011-01-01

    /MAPK pathway and requires active adenosine A(2A) receptors. Transport through GAT-3 is not affected by BDNF. To elucidate if BDNF affects trafficking of GAT-1 in astrocytes, we generated and infected astrocytes with a functional mutant of the rat GAT-1 (rGAT-1) in which the hemagglutinin (HA) epitope...

  5. Effects of geometric modulation and surface potential heterogeneity on electrokinetic flow and solute transport in a microchannel

    Science.gov (United States)

    Bera, Subrata; Bhattacharyya, S.

    2018-04-01

    A numerical investigation is performed on the electroosmotic flow (EOF) in a surface-modulated microchannel to induce enhanced solute mixing. The channel wall is modulated by placing surface-mounted obstacles of trigonometric shape along which the surface potential is considered to be different from the surface potential of the homogeneous part of the wall. The characteristics of the electrokinetic flow are governed by the Laplace equation for the distribution of external electric potential; the Poisson equation for the distribution of induced electric potential; the Nernst-Planck equations for the distribution of ions; and the Navier-Stokes equations for fluid flow simultaneously. These nonlinear coupled set of governing equations are solved numerically by a control volume method over the staggered system. The influence of the geometric modulation of the surface, surface potential heterogeneity and the bulk ionic concentration on the EOF is analyzed. Vortical flow develops near a surface modulation, and it becomes stronger when the surface potential of the modulated region is in opposite sign to the surface potential of the homogeneous part of the channel walls. Vortical flow also depends on the Debye length when the Debye length is in the order of the channel height. Pressure drop along the channel length is higher for a ribbed wall channel compared to the grooved wall case. The pressure drop decreases with the increase in the amplitude for a grooved channel, but increases for a ribbed channel. The mixing index is quantified through the standard deviation of the solute distribution. Our results show that mixing index is higher for the ribbed channel compared to the grooved channel with heterogeneous surface potential. The increase in potential heterogeneity in the modulated region also increases the mixing index in both grooved and ribbed channels. However, the mixing performance, which is the ratio of the mixing index to pressure drop, reduces with the rise in

  6. Study of electronic heat transport in plasma through diagnosis based on modulated electron cyclotron heating; Etudes de transport de la chaleur electronique par injection modulee d'ondes a la frequence cyclotronique electronique

    Energy Technology Data Exchange (ETDEWEB)

    Clemencon, A.; Guivarch, C

    2003-07-01

    In order to make nuclear fusion energetically profitable, it is crucial to heat and confine the plasma efficiently. Studying the behavior of the heat diffusion coefficient is a key issue in this matter. The use of modulated electron cyclotron heating as a diagnostic has suggested the existence of a transport barrier under certain plasma conditions. We have determined the solution to the heat transport equation, for several heat diffusion coefficient profiles. By comparing the analytical solutions with experimental data; we are able to study the heat diffusion coefficient profile. Thus, in certain experiments, we can confirm that the heat diffusion coefficient switches from low to high values at the radius where the electron cyclotron heat deposition is made. (authors)

  7. Delphi Accounts Receivable Module -

    Data.gov (United States)

    Department of Transportation — Delphi accounts receivable module contains the following data elements, but are not limited to customer information, cash receipts, line of accounting details, bill...

  8. Epigenetic Modulation of the Biophysical Properties of Drug-Resistant Cell Lipids to Restore Drug Transport and Endocytic Functions

    OpenAIRE

    Vijayaraghavalu, Sivakumar; Peetla, Chiranjeevi; Lu, Shan; Labhasetwar, Vinod

    2012-01-01

    In our recent studies exploring the biophysical characteristics of resistant cell lipids, and the role they play in drug transport, we demonstrated the difference of drug-resistant breast cancer cells from drug-sensitive cells in lipid composition and biophysical properties, suggesting that cancer cells acquire a drug-resistant phenotype through the alteration of lipid synthesis to inhibit intracellular drug transport to protect from cytotoxic effect. In cancer cells, epigenetic changes (e.g....

  9. Excitatory amino acid transporters: recent insights into molecular mechanisms, novel modes of modulation and new therapeutic possibilities

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Fahlke, Christoph; Bjørn-Yoshimoto, Walden Emil

    2015-01-01

    The five excitatory amino acid transporters (EAAT1–5) mediating the synaptic uptake of the major excitatory neurotransmitter glutamate are differently expressed throughout the CNS and at the synaptic level. Although EAATs are crucial for normal excitatory neurotransmission, explorations into the ......The five excitatory amino acid transporters (EAAT1–5) mediating the synaptic uptake of the major excitatory neurotransmitter glutamate are differently expressed throughout the CNS and at the synaptic level. Although EAATs are crucial for normal excitatory neurotransmission, explorations...

  10. Amphetamine Action at the Cocaine- and Antidepressant-Sensitive Serotonin Transporter Is Modulated by αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Montgomery, Therese R; Hofmaier, Tina

    2015-01-01

    Serotonergic neurotransmission is terminated by reuptake of extracellular serotonin (5-HT) by the high-affinity serotonin transporter (SERT). Selective 5-HT reuptake inhibitors (SSRIs) such as fluoxetine or escitalopram inhibit SERT and are currently the principal treatment for depression and anx...... and efflux at monoamine transporters are asymmetric processes that can be targeted separately. Ultimately, this may provide a molecular mechanism for putative drug developments to treat amphetamine addiction....

  11. Transport of Pb and Zn by carboxylate complexes in basinal ore fluids and related petroleum-field brines at 100°C: the influence of pH and oxygen fugacity

    Directory of Open Access Journals (Sweden)

    Giordano Thomas H

    2002-09-01

    Full Text Available It is well established through field observations, experiments, and chemical models that oxidation (redox state and pH exert a strong influence on the speciation of dissolved components and the solubility of minerals in hydrothermal fluids. log –pH diagrams were used to depict the influence of oxygen fugacity and pH on monocarboxylate- and dicarboxylate-transport of Pb and Zn in low-temperature (100°C hydrothermal ore fluids that are related to diagenetic processes in deep sedimentary basins, and allow a first-order comparison of Pb and Zn transport among proposed model fluids for Mississippi Valley-type (MVT and red-bed related base metal (RBRBM deposits in terms of their approximate pH and conditions. To construct these diagrams, total Pb and Zn concentrations and Pb and Zn speciation were calculated as a function of log and pH for a composite ore-brine with concentrations of major elements, total sulfur, and total carbonate that approximate the composition of MVT and RBRBM model ore fluids and modern basinal brines. In addition to acetate and malonate complexation, complexes involving the ligands Cl-, HS-, H2S, and OH- were included in the model of calculated total metal concentration and metal speciation. Also, in the model, Zn and Pb are competing with the common-rock forming metals Ca, Mg, Na, Fe, and Al for the same ligands. Calculated total Pb concentration and calculated total Zn concentration are constrained by galena and sphalerite solubility, respectively. Isopleths, in log –pH space, of the concentration of Pb and concentration of Zn in carboxylate (acetate + malonate complexes illustrate that the oxidized model fluids of T. H. Giordano (in Organic Acids in Geological Processes, ed. E. D. Pittman and M. D. Lewan, Springer-Verlag, New York, 1994, pp. 319–354 and G. M. Anderson (Econ. Geol., 1975, 70, 937–942 are capable of transporting sufficient amounts of Pb (up to 10 ppm and Zn (up to 100 ppm in the form of carboxylate

  12. Tunable GLUT-Hexose Binding and Transport via Modulation of Hexose C-3 Hydrogen-Bonding Capabilities.

    Science.gov (United States)

    Kumar Kondapi, Venkata Pavan; Soueidan, Olivier-Mohamad; Cheeseman, Christopher I; West, Frederick G

    2017-06-12

    The importance of the hydrogen bonding interactions in the GLUT-hexose binding process (GLUT=hexose transporter) has been demonstrated by studying the binding of structurally modified d-fructose analogues to GLUTs, and in one case its transport into cells. The presence of a hydrogen bond donor at the C-3 position of 2,5-anhydro-d-mannitol derivatives is essential for effective binding to GLUT5 and transport into tumor cells. Surprisingly, installation of a group that can function only as a hydrogen bond acceptor at C-3 resulted in selective recognition by GLUT1 rather than GLUT5. A fluorescently labelled analogue clearly showed GLUT-mediated transport and low efflux properties of the probe. This study reveals that a single positional modification of a 2,5-anhydro-d-mannitol derivative is sufficient to switch its binding preference from GLUT5 to GLUT1, and uncovers general scaffolds that are suitable for the potential selective delivery of molecular payloads into tumor cells via GLUT transport machinery. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Modulational effects in accelerators

    International Nuclear Information System (INIS)

    Satogata, T.

    1997-01-01

    We discuss effects of field modulations in accelerators, specifically those that can be used for operational beam diagnostics and beam halo control. In transverse beam dynamics, combined effects of nonlinear resonances and tune modulations influence diffusion rates with applied tune modulation has been demonstrated. In the longitudinal domain, applied RF phase and voltage modulations provide mechanisms for parasitic halo transport, useful in slow crystal extraction. Experimental experiences with transverse tune and RF modulations are also discussed

  14. Study on a transportation and emplacement system of pre-assembled EBS module for HLW geological disposal

    International Nuclear Information System (INIS)

    Awano, Toshihiko; Kanno, Takeshi; Katsumata, Syunsuke; Kosuge, Kazuhiro

    2009-01-01

    HLW disposal is one of the largest issue to utilize Nuclear power safely. In the past study, the concept, which buffer materials and Overpacked waste were transported into underground respectively, have shown. The concept of pre-assembled engineered barrier has advantage to simplify the logistics and emplacement procedure, however there are difficulties to support heavy weight of pre-assembled package by equipment under the condition of little clearance between tunnel and package. In this study, Combination of air bearing and two degree-of-freedom wheels were suggested for transportation, and air jack was suggested for unloading and emplacement system. Also, whole system for transportation and emplacement procedure was designed, and Scale model test was examined to evaluate the feasibility of these concept and functions. (author)

  15. Regulator of G protein signaling-12 modulates the dopamine transporter in ventral striatum and locomotor responses to psychostimulants.

    Science.gov (United States)

    Gross, Joshua D; Kaski, Shane W; Schroer, Adam B; Wix, Kimberley A; Siderovski, David P; Setola, Vincent

    2018-02-01

    Regulators of G protein signaling are proteins that accelerate the termination of effector stimulation after G protein-coupled receptor activation. Many regulators of G protein signaling proteins are highly expressed in the brain and therefore considered potential drug discovery targets for central nervous system pathologies; for example, here we show that RGS12 is highly expressed in microdissected mouse ventral striatum. Given a role for the ventral striatum in psychostimulant-induced locomotor activity, we tested whether Rgs12 genetic ablation affected behavioral responses to amphetamine and cocaine. RGS12 loss significantly decreased hyperlocomotion to lower doses of both amphetamine and cocaine; however, other outcomes of administration (sensitization and conditioned place preference) were unaffected, suggesting that RGS12 does not function in support of the rewarding properties of these psychostimulants. To test whether observed response changes upon RGS12 loss were caused by changes to dopamine transporter expression and/or function, we prepared crude membranes from the brains of wild-type and RGS12-null mice and measured dopamine transporter-selective [ 3 H]WIN 35428 binding, revealing an increase in dopamine transporter levels in the ventral-but not dorsal-striatum of RGS12-null mice. To address dopamine transporter function, we prepared striatal synaptosomes and measured [ 3 H]dopamine uptake. Consistent with increased [ 3 H]WIN 35428 binding, dopamine transporter-specific [ 3 H]dopamine uptake in RGS12-null ventral striatal synaptosomes was found to be increased. Decreased amphetamine-induced locomotor activity and increased [ 3 H]WIN 35428 binding were recapitulated with an independent RGS12-null mouse strain. Thus, we propose that RGS12 regulates dopamine transporter expression and function in the ventral striatum, affecting amphetamine- and cocaine-induced increases in dopamine levels that specifically elicit acute hyperlocomotor responses.

  16. Osmolality, temperature, and membrane lipid composition modulate the activity of betaine transporter BetP in Corynebacterium glutamicum

    DEFF Research Database (Denmark)

    Ozcan, Nuran; Ejsing, Christer S.; Shevchenko, Andrej

    2007-01-01

    The gram-positive soil bacterium Corynebacterium glutamicum, a major amino acid-producing microorganism in biotechnology, is equipped with several osmoregulated uptake systems for compatible solutes, which is relevant for the physiological response to osmotic stress. The most significant carrier......P activity. We further correlated the change in BetP regulation properties in cells grown at different temperatures to changes in the lipid composition of the plasma membrane. For this purpose, the glycerophospholipidome of C. glutamicum grown at different temperatures was analyzed by mass spectrometry using...... quantitative multiple precursor ion scanning. The molecular composition of glycerophospholipids was strongly affected by the growth temperature. The modulating influence of membrane lipid composition on BetP function was further corroborated by studying the influence of artificial modulation of membrane...

  17. Altered expression and modulation of activity-regulated cytoskeletal associated protein (Arc) in serotonin transporter knockout rats.

    NARCIS (Netherlands)

    Molteni, R.; Calabrese, F.; Maj, P.F.; Olivier, J.D.A.; Racagni, G.; Ellenbroek, A.A.; Riva, M.A.

    2009-01-01

    A gene variant in the human serotonin transporter (SERT) can increase the vulnerability to mood disorders. SERT knockout animals show similarities to the human condition and represent an important tool to investigate the mechanisms underlying the pathologic condition in humans. Along this line of

  18. Engineering of Ion Sensing by the Cystathionine beta-Synthase Module of the ABC Transporter OpuA

    NARCIS (Netherlands)

    Mahmood, Nik A. B. N.; Biemans-Oldehinkel, Esther; Poolman, Bert

    2009-01-01

    We have previously shown that the C-terminal cystathionine beta-synthase (CBS) domains of the nucleotide-binding domains of the ABC transporter OpuA, in conjunction with an anionic membrane surface function, act as sensor of internal ionic strength (I(in)). Here, we show that a surface-exposed

  19. Research and Development on Oxygen Transport Membranes at the Technical University of Denmark from Materials to Modules

    DEFF Research Database (Denmark)

    Kiebach, Wolff-Ragnar; Pirou, Stéven; Ovtar, Simona

    2016-01-01

    Oxygen transport membranes (OTMs) are inorganic, high temperature devices that have the potential to efficiently supply oxygen to combustion processes, for example for oxy-fired (biomass) gasification or in the cement and steel industry. This work reviews aspects of material selection, design...

  20. Modulation of Xenobiotic Metabolizing Enzyme and Transporter Gene Expression in Primary Cultures of Human Hepatocytes by ToxCast Chemicals

    Science.gov (United States)

    ToxCast chemicals were assessed for induction or suppression of xenobiotic metabolizing enzyme and transporter gene expression using primary human hepatocytes. The mRNA levels of 14 target and 2 control genes were measured: ABCB1, ABCB11, ABCG2, SLCO1B1, CYP1A1, CYP1A2, CYP2B6, C...

  1. Xenobiotic-Metabolizing Enzyme and Transporter Gene Expression in Primary Cultures of Human Hepatocytes Modulated by Toxcast Chemicals

    Science.gov (United States)

    Primary human hepatocyte cultures are useful in vitro model systems of human liver because when cultured under appropriate conditions the hepatocytes retain liver-like functionality such as metabolism, transport, and cell signaling. This model system was used to characterize the ...

  2. Functional modulation of the glutamate transporter variant GLT1b by the PDZ domain protein PICK1

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Borre, Lars; Braunstein, Thomas H

    2013-01-01

    The dominant glutamate transporter isoform in the mammalian brain, GLT1, exists as at least three splice variants, GLT1a, GLT1b, and GLT1c. GLT1b interacts with the scaffold protein PICK1 (protein interacting with kinase C1), which is implicated in glutamatergic neurotransmission via its regulato...

  3. Drug transporter gene expression in human colorectal tissue and cell lines: modulation with antiretrovirals for microbicide optimization.

    Science.gov (United States)

    Mukhopadhya, Indrani; Murray, Graeme I; Berry, Susan; Thomson, John; Frank, Bruce; Gwozdz, Garry; Ekeruche-Makinde, Julia; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

    2016-02-01

    The objectives of this study were to comprehensively assess mRNA expression of 84 drug transporters in human colorectal biopsies and six representative cell lines, and to investigate the alteration of drug transporter gene expression after exposure to three candidate microbicidal antiretroviral (ARV) drugs (tenofovir, darunavir and dapivirine) in the colorectal epithelium. The outcome of the objectives informs development of optimal ARV-based microbicidal formulations for prevention of HIV-1 infection. Drug transporter mRNA expression was quantified from colorectal biopsies and cell lines by quantitative real-time PCR. Relative mRNA expression was quantified in Caco-2 cells and colorectal explants after induction with ARVs. Data were analysed using Pearson's product moment correlation (r), hierarchical clustering and principal component analysis (PCA). Expression of 58 of the 84 transporters was documented in colorectal biopsies, with genes for CNT2, P-glycoprotein (P-gp) and MRP3 showing the highest expression. No difference was noted between individual subjects when analysed by age, gender or anatomical site (rectum or recto-sigmoid) (r = 0.95-0.99). High expression of P-gp and CNT2 proteins was confirmed by immunohistochemical staining. Similarity between colorectal tissue and cell-line drug transporter gene expression was variable (r = 0.64-0.84). PCA showed distinct clustering of human colorectal biopsy samples, with the Caco-2 cells defined as the best surrogate system. Induction of Caco-2 cell lines with ARV drugs suggests that darunavir-based microbicides incorporating tenofovir may result in drug-drug interactions likely to affect distribution of individual drugs to sub-epithelial target cells. These findings will help optimize complex formulations of rectal microbicides to realize their full potential as an effective approach for pre-exposure prophylaxis against HIV-1 infection. © The Author 2015. Published by Oxford University Press on behalf of the

  4. Modelling reactive material transport in the near field of a repository for radioactive waste. Coupling the EMOS near field modules CLAYPOS and LOPOS with thermodynamic equilibrium calculations

    International Nuclear Information System (INIS)

    Moog, H.C.; Keesmann, S.M.

    2007-02-01

    This paper reports on the project ''Coupling transport models with thermodynamic equilibrium calculations'' - short title EQLINK, promotion code number 02 E 9723 - in the which the scope for coupling thermodynamic equilibrium model calculations with EMOS was expanded and improved. The first step was to inquire into the current state of research on radiolytic processes. It transpired that there is currently no conclusive description of radiolytic processes. The existing descriptions are too complex and too narrowly geared to specific scenarios to allow a general view on radiolytic processes, which would be a prerequisite for creating suitable long-term geochemical safety analysis modules. It appears that the approximation calculations implemented in EMOS tend to overestimate rather than underestimate radiolytic gas formation. The thermodynamic database which is used at GRS (Society for Plant and Reactor Safety) as a basis for coupled transport calculations has been updated. For this purpose the radionuclide database of the Institut fuer Nukleare Entsorgung (INE = Institute for Nuclear Disposal) was converted to an in-house format which permits creating parameter files for specific requirements. The data of the INE comprise thermodynamic parameters such as equilibrium constants, Gibbs free enthalpies of formation, enthalpies and entropies of formation and Pitzer parameters, which are required for model calculations on high-saline solutions. The database for low-saline solutions which had been developed by PSI/NAGRA for calculations with CLAYPOS was also adopted. Both parameter sets were subjected to test calculations to detect any errors that might have occurred during the data transfer. It is thus now possible to perform coupled transport calculations with the EMOS modules LOPOS and CLAYPOS according to the state of the art of geochemical research. The EQLINK interface which had been developed in an earlier project, titled ''Development of a model for describing the

  5. RESEARCH ABOUT THE USERS´ PERCEPTION OF ACCOUNTING AND TAX BOOKKEEPING MODULES OF AN ERP SYSTEM FOR THE CARGO AND PASSENGERS ROAD TRANSPORTATION SECTOR

    Directory of Open Access Journals (Sweden)

    Ivam Ricardo Peleias

    2009-10-01

    Full Text Available This research evaluated the users´perception of accounting and tax bookkeeping modules of an ERP – Enterprise Resources Planning System for the cargo and passengers road transportation sector. It´s a survey research, which combined empiric investigation, bibliographical review, as well as field research. It was applied a questionnaire containing 20 questions to characterize the sample and 30 assertive ones, answered by 37 users of the system. The collected data were treated by Qualitative Analysis, Descriptive Statistics, Cluster Analysis and Comparative Analysis among the clusters. The results demonstrate how these users perceive the importance and the facilities with the use of the system, as well as grouped such users in 3 opinion clusters (optimistic, realists and pessimistic and indicated points that can be improved in the system.

  6. Epigenetic modulation of the biophysical properties of drug-resistant cell lipids to restore drug transport and endocytic functions.

    Science.gov (United States)

    Vijayaraghavalu, Sivakumar; Peetla, Chiranjeevi; Lu, Shan; Labhasetwar, Vinod

    2012-09-04

    In our recent studies exploring the biophysical characteristics of resistant cell lipids, and the role they play in drug transport, we demonstrated the difference of drug-resistant breast cancer cells from drug-sensitive cells in lipid composition and biophysical properties, suggesting that cancer cells acquire a drug-resistant phenotype through the alteration of lipid synthesis to inhibit intracellular drug transport to protect from cytotoxic effect. In cancer cells, epigenetic changes (e.g., DNA hypermethylation) are essential to maintain this drug-resistant phenotype. Thus, altered lipid synthesis may be linked to epigenetic mechanisms of drug resistance. We hypothesize that reversing DNA hypermethylation in resistant cells with an epigenetic drug could alter lipid synthesis, changing the cell membrane's biophysical properties to facilitate drug delivery to overcome drug resistance. Herein we show that treating drug-resistant breast cancer cells (MCF-7/ADR) with the epigenetic drug 5-aza-2'-deoxycytidine (decitabine) significantly alters cell lipid composition and biophysical properties, causing the resistant cells to acquire biophysical characteristics similar to those of sensitive cell (MCF-7) lipids. Following decitabine treatment, resistant cells demonstrated increased sphingomyelinase activity, resulting in a decreased sphingomyelin level that influenced lipid domain structures, increased membrane fluidity, and reduced P-glycoprotein expression. Changes in the biophysical characteristics of resistant cell lipids facilitated doxorubicin transport and restored endocytic function for drug delivery with a lipid-encapsulated form of doxorubicin, enhancing the drug efficacy. In conclusion, we have established a new mechanism for efficacy of an epigenetic drug, mediated through changes in lipid composition and biophysical properties, in reversing cancer drug resistance.

  7. cGMP-dependent protein kinase Iα associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake

    Directory of Open Access Journals (Sweden)

    Steiner Jennifer A

    2009-08-01

    Full Text Available Abstract Background The Na+/Cl--dependent serotonin (5-hydroxytryptamine, 5-HT transporter (SERT is a critical element in neuronal 5-HT signaling, being responsible for the efficient elimination of 5-HT after release. SERTs are not only targets for exogenous addictive and therapeutic agents but also can be modulated by endogenous, receptor-linked signaling pathways. We have shown that neuronal A3 adenosine receptor activation leads to enhanced presynaptic 5-HT transport in vitro and an increased rate of SERT-mediated 5-HT clearance in vivo. SERT stimulation by A3 adenosine receptors derives from an elevation of cGMP and subsequent activation of both cGMP-dependent protein kinase (PKG and p38 mitogen-activated protein kinase. PKG activators such as 8-Br-cGMP are known to lead to transporter phosphorylation, though how this modification supports SERT regulation is unclear. Results In this report, we explore the kinase isoform specificity underlying the rapid stimulation of SERT activity by PKG activators. Using immortalized, rat serotonergic raphe neurons (RN46A previously shown to support 8-Br-cGMP stimulation of SERT surface trafficking, we document expression of PKGI, and to a lower extent, PKGII. Quantitative analysis of staining profiles using permeabilized or nonpermeabilized conditions reveals that SERT colocalizes with PKGI in both intracellular and cell surface domains of RN46A cell bodies, and exhibits a more restricted, intracellular pattern of colocalization in neuritic processes. In the same cells, SERT demonstrates a lack of colocalization with PKGII in either intracellular or surface membranes. In keeping with the ability of the membrane permeant kinase inhibitor DT-2 to block 8-Br-cGMP stimulation of SERT, we found that DT-2 treatment eliminated cGMP-dependent kinase activity in PKGI-immunoreactive extracts resolved by liquid chromatography. Similarly, treatment of SERT-transfected HeLa cells with small interfering RNAs targeting

  8. Modulation of the human equilibrative nucleoside transporter1 (hENT1) activity by IL-4 and PMA in B cells from chronic lymphocytic leukemia.

    Science.gov (United States)

    Fernández Calotti, Paula; Galmarini, Carlos María; Cañones, Cristian; Gamberale, Romina; Saénz, Daniel; Avalos, Julio Sánchez; Chianelli, Mónica; Rosenstein, Ruth; Giordano, Mirta

    2008-02-15

    Nucleoside transporters (NTs) are essential for the uptake of therapeutic nucleoside analogs, broadly used in cancer treatment. The mechanisms responsible for NT regulation are largely unknown. IL-4 is a pro-survival signal for chronic lymphocytic leukemia (CLL) cells and has been shown to confer resistance to nucleoside analogs. The aim of this study was to investigate whether IL-4 is able to modulate the expression and function of the human equilibrative NT1 (hENT1) in primary cultures of CLL cells and, consequently, to affect cytotoxicity induced by therapeutic nucleosides analogs. We found that treatment with IL-4 (20 ng/ml for 24 h) increased mRNA hENT1 expression in CLL cells without affecting that of normal B cells. Given that the enhanced mRNA levels of hENT1 in CLL cells did not result in increased transport activity, we examined the possibility that hENT1 induced by IL-4 may require post-translational modifications to become active. We found that the acute stimulation of PKC in IL-4-treated CLL cells by short-term incubation with PMA significantly increased hENT1 transport activity and favoured fludarabine-induced apoptosis. By contrast, and in line with previous reports, IL-4 plus PMA protected CLL cells from a variety of cytotoxic agents. Our findings indicate that the combined treatment with IL-4 and PMA enhances hENT1 activity and specifically sensitizes CLL cells to undergo apoptosis induced by fludarabine.

  9. Carrier transfer and magneto-transport in single modulation-doped V-grooved quantum wire modified by ion implantation

    International Nuclear Information System (INIS)

    Huang, S.H.; Chen Zhanghai; Wang, F.Z.; Shen, S.C.; Tan, H.H.; Fu, L.; Fraser, M.; Jagadish, C.

    2006-01-01

    A single Al 0.5 Ga 0.5 As/GaAs V-grooved quantum wire modified by selective ion implantation and rapid thermal annealing was investigated by using spatially resolved micro-photoluminescence spectroscopy and magneto-resistance measurements. The results of spatially resolved photoluminescence indicate that the ion-implantation-induced quantum well intermixing significantly raises the electronic sub-band energies in the side quantum wells (SQWs) and vertical quantum wells, and a more efficient accumulation of electrons in the quantum wires is achieved. Processes of real space carrier transfer from the SQW to the quantum wire was experimentally observed, and showed the blocking effect of carrier transfer due to the existence of the necking quantum well region. Furthermore, magneto-transport investigation on the ion-implanted quantum wire samples shows the quasi-one-dimensional intrinsic motion of electrons, which is important for the design and the optimization of one-dimensional electronic devices

  10. Full-scale demonstration of EBS construction technology II. Design, manufacturing and transportation of pre-fabricated EBS module (PEM)

    International Nuclear Information System (INIS)

    Asano, Hidekazu; Toguri, Satohito; Iwata, Yumiko; Kawakami, Susumu; Nagasawa, Yuji; Yoshida, Takeshi

    2008-01-01

    PEM was investigated as a full-scale demonstration for the design, manufacturing and construction by using simulated buffer material and overpack in consideration of horizontal emplacement. Also near full-scale tests were conducted to examine the applicability of air-bearing system which can be used to transport a heavy load at the drift tunnel as for PEM. With regard to PEM casing, design requirements were selected from the viewpoints of EBS performance and operation safety issues. The construction procedure was examined in consideration of the shapes of buffer material, which are previously positioned inside the casing. And design procedure of the casing was also examined and presented. A full-scale PEM casing as a longitudinally two-part divided cylinder type with connection flanges was manufactured by using carbon steel plate. The wall thickness of this non-leak tight type PEM casing was evaluated its mechanical integrity by 2-dimensional stress analysis in consideration of the emplacement condition on the drift tunnel basement. Mechanical integrity of a percolated type casing was also examined its mechanical integrity. Air-bearing unit, which originally apply to a flat/smooth surface, was modified to fit a curved surface of the drift tunnel. Two units were aligned with two parallel lines, which estimate to be able to lift 12 tons, about two-fifth of the total weight of full scale PEM. On the conducted transportation tests of the air-bearing units, considering the surface roughness of the drift tunnel, especially for its unevenness, capability and availability of the run-over such gaps were investigated. And effect of covering sheets which can improve the gapped surface into relatively smooth was also examined by using several candidate materials. Through these tests, combination of the covering sheets and the maximum available height difference were evaluated and identified. Also the maximum traction force to toe the loading was measured to design the air

  11. Charge transport and magnetoresistance of G4-DNA molecular device modulated by counter ions and dephasing effect

    International Nuclear Information System (INIS)

    Kang, Da-wei; Sun, Meng-le; Zuo, Zheng-wei; Wang, Hui-xian; Lv, Shi-jie; Li, Xin-zhong; Li, Li-ben

    2016-01-01

    The charge transport properties of the G4-DNA molecular device in the presence of counter ions and dephasing effect are investigated based on the Green function method and Landauer–Büttiker theory. The currents through the G4-DNA molecular device depend on the interference patterns at different coupling configurations. There is an effective electrostatic interaction between the counter ions and the G4-DNA molecule which introduces disorder into the on-site energies of G bases. The current through the device can be enhanced by the small disorder which avoids the strong interference of electrons at the same energy in some coupling configurations, however the diagonal disorder can suppress the overall current due to the Anderson localization of charge carriers when the disorder is large. In the presence of dephasing effect the current through the device at all coupling configurations can be enhanced as a result of the phase coherence losing of electron. As for the magnetic field response, the magnetoresistance of the device is always suppressed by the counter ions and dephasing effect. - Highlights: • The counter ions can some times enhance the current through G4-DNA molecule. • The dephasing effect can enhance the current of the device at all four coupling configurations. • The magnetoresistance is always suppressed by the counter ions and dephasing effect.

  12. The mitochondrial phosphate transporters modulate plant responses to salt stress via affecting ATP and gibberellin metabolism in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Wei Zhu

    Full Text Available The mitochondrial phosphate transporter (MPT plays crucial roles in ATP production in plant cells. Three MPT genes have been identified in Arabidopsis thaliana. Here we report that the mRNA accumulations of AtMPTs were up-regulated by high salinity stress in A. thaliana seedlings. And the transgenic lines overexpressing AtMPTs displayed increased sensitivity to salt stress compared with the wild-type plants during seed germination and seedling establishment stages. ATP content and energy charge was higher in overexpressing plants than those in wild-type A. thaliana under salt stress. Accordingly, the salt-sensitive phenotype of overexpressing plants was recovered after the exogenous application of atractyloside due to the change of ATP content. Interestingly, Genevestigator survey and qRT-PCR analysis indicated a large number of genes, including those related to gibberellin synthesis could be regulated by the energy availability change under stress conditions in A. thaliana. Moreover, the exogenous application of uniconazole to overexpressing lines showed that gibberellin homeostasis was disturbed in the overexpressors. Our studies reveal a possible link between the ATP content mediated by AtMPTs and gibberellin metabolism in responses to high salinity stress in A. thaliana.

  13. Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G Protein, Gαs.

    Science.gov (United States)

    Erb, Samuel J; Schappi, Jeffrey M; Rasenick, Mark M

    2016-09-16

    Depression is a significant public health problem for which currently available medications, if effective, require weeks to months of treatment before patients respond. Previous studies have shown that the G protein responsible for increasing cAMP (Gαs) is increasingly localized to lipid rafts in depressed subjects and that chronic antidepressant treatment translocates Gαs from lipid rafts. Translocation of Gαs, which shows delayed onset after chronic antidepressant treatment of rats or of C6 glioma cells, tracks with the delayed onset of therapeutic action of antidepressants. Because antidepressants appear to specifically modify Gαs localized to lipid rafts, we sought to determine whether structurally diverse antidepressants accumulate in lipid rafts. Sustained treatment of C6 glioma cells, which lack 5-hydroxytryptamine transporters, showed marked concentration of several antidepressants in raft fractions, as revealed by increased absorbance and by mass fingerprint. Closely related molecules without antidepressant activity did not concentrate in raft fractions. Thus, at least two classes of antidepressants accumulate in lipid rafts and effect translocation of Gαs to the non-raft membrane fraction, where it activates the cAMP-signaling cascade. Analysis of the structural determinants of raft localization may both help to explain the hysteresis of antidepressant action and lead to design and development of novel substrates for depression therapeutics. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. MPN-1 : A computation module for the solution of transport equation in multiregions by P sub(N) method

    International Nuclear Information System (INIS)

    Yamaguchi, M.; Maiorino, J.R.

    1981-11-01

    The MPN-1, which is a computer program made in FORTRAN IV is described. The MPN-1 uses P sub(N) method to solve the one-speed, anisotropic linear steady-state transport equation in non-multiplying multiregions, slab geometry. The MPN-1 allows a maximum number of 12 regions, and maximum order of approximation, N=15. Besides, the anisotropic scattering is treated by an expansion in Legendre polynomial up to maximum degree of L=15. The boundary conditions used are: I) free surface; II) isotropic incidence; III) cosine incidence (aμ sup(α1 + bμ sup(α2) + cμ sup(α3)); IV) monodirectional incidence (delta function); V) total reflection. The required input are: order of approximation P sub(N'), average number of secondary particles in each region, external sources, thickness of each region, coefficients in a Legendre expansion of the transfer function in each region, and type of boundary conditions at the boundaries. The output are: albedo, transmission factor, disadvantage factor, total and angular fluxes and current. (Author) [pt

  15. The metal chaperone Atox1 regulates the activity of the human copper transporter ATP7B by modulating domain dynamics.

    Science.gov (United States)

    Yu, Corey H; Yang, Nan; Bothe, Jameson; Tonelli, Marco; Nokhrin, Sergiy; Dolgova, Natalia V; Braiterman, Lelita; Lutsenko, Svetlana; Dmitriev, Oleg Y

    2017-11-03

    The human transporter ATP7B delivers copper to the biosynthetic pathways and maintains copper homeostasis in the liver. Mutations in ATP7B cause the potentially fatal hepatoneurological disorder Wilson disease. The activity and intracellular localization of ATP7B are regulated by copper, but the molecular mechanism of this regulation is largely unknown. We show that the copper chaperone Atox1, which delivers copper to ATP7B, and the group of the first three metal-binding domains (MBD1-3) are central to the activity regulation of ATP7B. Atox1-Cu binding to ATP7B changes domain dynamics and interactions within the MBD1-3 group and activates ATP hydrolysis. To understand the mechanism linking Atox1-MBD interactions and enzyme activity, we have determined the MBD1-3 conformational space using small angle X-ray scattering and identified changes in MBD dynamics caused by apo -Atox1 and Atox1-Cu by solution NMR. The results show that copper transfer from Atox1 decreases domain interactions within the MBD1-3 group and increases the mobility of the individual domains. The N-terminal segment of MBD1-3 was found to interact with the nucleotide-binding domain of ATP7B, thus physically coupling the domains involved in copper binding and those involved in ATP hydrolysis. Taken together, the data suggest a regulatory mechanism in which Atox1-mediated copper transfer activates ATP7B by releasing inhibitory constraints through increased freedom of MBD1-3 motions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Modulation of redox regulatory molecules and electron transport chain activity in muscle of air breathing fish Heteropneustes fossilis under air exposure stress.

    Science.gov (United States)

    Paital, Biswaranjan

    2014-01-01

    Responses of redox regulatory system to long-term survival (>18 h) of the catfish Heteropneustes fossilis in air are not yet understood. Lipid and protein oxidation level, oxidant (H2O2) generation, antioxidative status (levels of superoxide dismutase, catalase, glutathione peroxidase and reductase, ascorbic acid and non-protein sulfhydryl) and activities of respiratory complexes (I, II, III and IV) in mitochondria were investigated in muscle of H. fossilis under air exposure condition (0, 3, 6, 12 and 18 h at 25 °C). The increased levels of both H2O2 and tissue oxidation were observed due to the decreased activities of antioxidant enzymes in muscle under water deprivation condition. However, ascorbic acid and non-protein thiol groups were the highest at 18 h air exposure time. A linear increase in complex II activity with air exposure time and an increase up to 12 h followed by a decrease in activity of complex I at 18 h were observed. Negative correlation was observed for complex III and V activity with exposure time. Critical time to modulate the above parameters was found to be 3 h air exposure. Dehydration induced oxidative stress due to modulation of electron transport chain and redox metabolizing enzymes in muscle of H. fossilis was clearly observed. Possible contribution of redox regulatory system in muscle tissue of the fish for long-term survival in air is elucidated. Results of the present study may be useful to understand the redox metabolism in muscle of fishes those are exposed to air in general and air breathing fishes in particular.

  17. A novel FbFP-based biosensor toolbox for sensitive in vivo determination of intracellular pH.

    Science.gov (United States)

    Rupprecht, Christian; Wingen, Marcus; Potzkei, Janko; Gensch, Thomas; Jaeger, Karl-Erich; Drepper, Thomas

    2017-09-20

    The intracellular pH is an important modulator of various bio(techno)logical processes such as enzymatic conversion of metabolites or transport across the cell membrane. Changes of intracellular pH due to altered proton distribution can thus cause dysfunction of cellular processes. Consequently, accurate monitoring of intracellular pH allows elucidating the pH-dependency of (patho)physiological and biotechnological processes. In this context, genetically encoded biosensors represent a powerful tool to determine intracellular pH values non-invasively and with high spatiotemporal resolution. We have constructed a toolbox of novel genetically encoded FRET-based pH biosensors (named Fluorescence Biosensors for pH or FluBpH) that utilizes the FMN-binding fluorescent protein EcFbFP as donor domain. In contrast to many fluorescent proteins of the GFP family, EcFbFP exhibits a remarkable tolerance towards acidic pH (pK a ∼3.2). To cover the broad range of physiologically relevant pH values, three EYFP variants exhibiting pK a values of 5.7, 6.1 and 7.5 were used as pH-sensing FRET acceptor domains. The resulting biosensors FluBpH 5.7, FluBpH 6.1 and FluBpH 7.5 were calibrated in vitro and in vivo to accurately evaluate their pH indicator properties. To demonstrate the in vivo applicability of FluBpH, changes of intracellular pH were ratiometrically measured in E. coli cells during acid stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Estrous cycle modulation of extracellular serotonin in mediobasal hypothalamus: role of the serotonin transporter and terminal autoreceptors.

    Science.gov (United States)

    Maswood, S; Truitt, W; Hotema, M; Caldarola-Pastuszka, M; Uphouse, L

    1999-06-12

    In vivo microdialysis was used to examine extracellular serotonin (5-HT) in the mediobasal hypothalamus (MBH) of male and female Fischer (CDF-344) rats. Females from the stages of diestrus, proestrus, and estrus were used. Additionally, ovariectomized rats, primed subcutaneously (s.c.) with estradiol benzoate or estradiol benzoate plus progesterone were examined. Extracellular 5-HT in the MBH varied with stage of the estrous cycle and with the light/dark cycle. Proestrous females had the highest microdialysate concentrations of 5-HT during the light portion of the light/dark cycle and lowest concentrations during the dark portion of the cycle. Diestrous females had the highest levels during the dark portion of the cycle, while males and estrous females showed little change between light and dark portions of the cycle. In ovariectomized rats, there was no effect of 2.5 microg or 25 microg estradiol benzoate (s.c.) on extracellular 5-HT; but the addition of 500 microg progesterone, 48 h after estrogen priming, reduced microdialysate 5-HT near the threshold for detection. In intact females and in males, reverse perfusion with 3 microM fluoxetine, a selective serotonin reuptake inhibitor (SSRI), or 2 microM methiothepin, a 5-HT receptor antagonist, increased microdialysate concentrations of 5-HT. Estrous females and males showed nearly a 4-fold increase in microdialysate 5-HT in response to fluoxetine while smaller responses were seen in diestrous and proestrous rats. In contrast, proestrous rats showed the largest response to methiothepin. Estrous females showed a delayed response to methiothepin, but there was no methiothepin-induced increase in extracellular 5-HT in males. These findings are discussed in reference to the suggestion that extracellular 5-HT in the MBH is regulated in a manner that is gender and estrous cycle dependent. The 5-HT terminal autoreceptor may exert a greater role in proestrous females; the serotonin transporter appears to play a more active

  19. Galectin-3 silencing inhibits epirubicin-induced ATP binding cassette transporters and activates the mitochondrial apoptosis pathway via β-catenin/GSK-3β modulation in colorectal carcinoma.

    Directory of Open Access Journals (Sweden)

    Yung-Kuo Lee

    Full Text Available Multidrug resistance (MDR, an unfavorable factor compromising the treatment efficacy of anticancer drugs, involves the upregulation of ATP binding cassette (ABC transporters and induction of galectin-3 signaling. Galectin-3 plays an anti-apoptotic role in many cancer cells and regulates various pathways to activate MDR. Thus, the inhibition of galectin-3 has the potential to enhance the efficacy of the anticancer drug epirubicin. In this study, we examined the effects and mechanisms of silencing galectin-3 via RNA interference (RNAi on the β-catenin/GSK-3β pathway in human colon adenocarcinoma Caco-2 cells. Galectin-3 knockdown increased the intracellular accumulation of epirubicin in Caco-2 cells; suppressed the mRNA expression of galectin-3, β-catenin, cyclin D1, c-myc, P-glycoprotein (P-gp, MDR-associated protein (MRP 1, and MRP2; and downregulated the protein expression of P-gp, cyclin D1, galectin-3, β-catenin, c-Myc, and Bcl-2. Moreover, galectin-3 RNAi treatment significantly increased the mRNA level of GSK-3β, Bax, caspase-3, and caspase-9; remarkably increased the Bax-to-Bcl-2 ratio; and upregulated the GSK-3β and Bax protein expressions. Apoptosis was induced by galectin-3 RNAi and/or epirubicin as demonstrated by chromatin condensation, a higher sub-G1 phase proportion, and increased caspase-3 and caspase-9 activity, indicating an intrinsic/mitochondrial apoptosis pathway. Epirubicin-mediated resistance was effectively inhibited via galectin-3 RNAi treatment. However, these phenomena could be rescued after galectin-3 overexpression. We show for the first time that the silencing of galectin-3 sensitizes MDR cells to epirubicin by inhibiting ABC transporters and activating the mitochondrial pathway of apoptosis through modulation of the β-catenin/GSK-3β pathway in human colon cancer cells.

  20. Photovoltaic module and interlocked stack of photovoltaic modules

    Science.gov (United States)

    Wares, Brian S.

    2014-09-02

    One embodiment relates to an arrangement of photovoltaic modules configured for transportation. The arrangement includes a plurality of photovoltaic modules, each photovoltaic module including a frame. A plurality of individual male alignment features and a plurality of individual female alignment features are included on each frame. Adjacent photovoltaic modules are interlocked by multiple individual male alignment features on a first module of the adjacent photovoltaic modules fitting into and being surrounded by corresponding individual female alignment features on a second module of the adjacent photovoltaic modules. Other embodiments, features and aspects are also disclosed.

  1. Development and validation of the aerosol transport module gamma-FP for evaluating radioactive fission product source terms in a VHTR

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Churl; Lim, Hong Sik [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-12-15

    Predicting radioactive fission product (FP) behaviors in the reactor coolant system and the containment of a nuclear power plant (NPP) is one of the major concerns in the field of reactor safety, since the amount of radioactive FP released into the environment during the postulated accident sequences is one of the major regulatory issues. Radioactive FPs circulating in the primary coolant loop and released into the containment are basically in the form of gas or aerosol. In this study, a multi-component and multi-sectional analysis module for aerosol fission products has been developed based on the MAEROS model, and the aerosol transport model has been developed and verified against an analytic solution. The deposition of aerosol FPs to the surrounding structural surfaces is modeled with recent research achievements. The developed aerosol analysis model has been successfully validated against the STORM SR-11 experimental data, which is International Standard Problem No. 40. Future studies include the development of the resuspension, growth, and chemical reaction models of aerosol fission products.

  2. PH og modernismen

    DEFF Research Database (Denmark)

    Ahnfeldt-Mollerup, Merete

    2012-01-01

    Artiklen kaster et kritisk blik på Poul Henningsens samfundsanalyse og dennes sammenhæng med hans design. PH ses i en bredere national og international sammenhæng. Diskussion af designmetoder, æstetik og Bauhaus.......Artiklen kaster et kritisk blik på Poul Henningsens samfundsanalyse og dennes sammenhæng med hans design. PH ses i en bredere national og international sammenhæng. Diskussion af designmetoder, æstetik og Bauhaus....

  3. Phénomènes dépendants du spin dans des structures à un puits quantique CdMnTe à modulation de dopage de type-n

    OpenAIRE

    Teran , Francisco Jose

    2001-01-01

    The study of the electronic and magnetic properties of n-type modulation doped CdMnTe quantum well structures has allowed to investigate the sp-d exchange interaction between 2D electrons and localized magnetic moments of Mn2+ ions. Such exchange interaction realigns the electronic spin states leading to a giant Zeeman splitting which deeply modifies the optical and electronic properties of the semiconductor host. At low magnetic fields, the sp-d exchange interaction term can be successfully ...

  4. PhD on Track – designing learning for PhD students

    Directory of Open Access Journals (Sweden)

    Gunhild Austrheim

    2013-12-01

    Full Text Available Three years ago we started the project "Information Management for Knowledge Creation". The project was initiated to create online information literacy modules for PhD students. The result of our endeavours, PhD on Track, will be launched in May 2013. The initial stage of the project was mapping out the information behaviour of PhD students, as well as what services they require from the library through a literature review and a focus group study. The findings of these inquiries formed the knowledge base from which we developed our information literacy modules. Our paper will focus on the interaction between content production and user testing when creating PhD on Track. Methods: User testing has been employed throughout the production stage. We have tested navigation and organisation of the web site, content and usability. The project team have conducted expert testing. Analysis: The results from our user testing have played an important part in decisions concerning content production. Our working hypothesis was that the PhD students would want an encyclopaedic website, a place to quickly find answers. However, the user tests revealed that PhD students understood and expected the website to be learning modules. Conclusions: The PhD students in the tests agreed that a site such as this would be useful, especially to new PhD students. They also liked the design, but had some qualms with the level of information. They preferred shorter text, but with more depth. The students would likewise have preferred more practical examples, more illustrations and more discipline specific information. The current content of PhD on Track reflects the feedback from the user testing. We have retained initial ideas such as one section for reviewing and discovering research literature and one section for publishing PhD research work. In addition, we have included more practical examples to indicate efficient workflows or relevant actions in context. Illustrations

  5. Low pH Cements

    International Nuclear Information System (INIS)

    Savage, David; Benbow, Steven

    2007-05-01

    The development of low-pH cements for use in geological repositories for radioactive waste stems from concerns over the potential for deleterious effects upon the host rock and other EBS materials (notably bentonite) under the hyperalkaline conditions (pH > 12) of cement pore fluids. Low pH cement (also known as low heat cement) was developed by the cement industry for use where large masses of cement (e.g. dams) could cause problems regarding heat generated during curing. In low pH cements, the amount of cement is reduced by substitution of materials such as fly ash, blast furnace slag, silica fume, and/or non-pozzolanic silica flour. SKB and Posiva have ruled out the use of blast furnace slag and fly-ash and are focusing on silica fume as a blending agent. Currently, no preferred composition has been identified by these agencies. SKB and Posiva have defined a pH limit ≤ 11 for cement grout leachates. To attain this pH, blending agents must comprise at least 50 wt % of dry materials. Because low pH cement has little, or no free portlandite, the cement consists predominantly of calcium silicate hydrate (CSH) gel with a Ca/Si ratio ≤ 0.8. Although there are potential implications for the performance of the spent fuel and cladding due to the presence of hyperalkaline fluids from cement, the principal focus for safety assessment lies with the behaviour of bentonite. There are a number of potential constraints on the interaction of hyperalkaline cement pore fluids with bentonite, including mass balance, thermodynamic issues, mass transport, and kinetics, but none of these is likely to be limiting if conventional OPC cements are employed in repository construction. Nevertheless: Low-pH cements may supply approximately 50 % less hydroxyl ions than conventional OPC for a given volume of cement, but mass balance constraints are complicated by the uncertainty concerning the type of secondary minerals produced during cement-bentonite interaction. The change of aqueous

  6. Low pH Cements

    Energy Technology Data Exchange (ETDEWEB)

    Savage, David; Benbow, Steven [Quintessa Ltd., Henley-on-Thames (United Kingdom)

    2007-05-15

    The development of low-pH cements for use in geological repositories for radioactive waste stems from concerns over the potential for deleterious effects upon the host rock and other EBS materials (notably bentonite) under the hyperalkaline conditions (pH > 12) of cement pore fluids. Low pH cement (also known as low heat cement) was developed by the cement industry for use where large masses of cement (e.g. dams) could cause problems regarding heat generated during curing. In low pH cements, the amount of cement is reduced by substitution of materials such as fly ash, blast furnace slag, silica fume, and/or non-pozzolanic silica flour. SKB and Posiva have ruled out the use of blast furnace slag and fly-ash and are focusing on silica fume as a blending agent. Currently, no preferred composition has been identified by these agencies. SKB and Posiva have defined a pH limit {<=} 11 for cement grout leachates. To attain this pH, blending agents must comprise at least 50 wt % of dry materials. Because low pH cement has little, or no free portlandite, the cement consists predominantly of calcium silicate hydrate (CSH) gel with a Ca/Si ratio {<=} 0.8. Although there are potential implications for the performance of the spent fuel and cladding due to the presence of hyperalkaline fluids from cement, the principal focus for safety assessment lies with the behaviour of bentonite. There are a number of potential constraints on the interaction of hyperalkaline cement pore fluids with bentonite, including mass balance, thermodynamic issues, mass transport, and kinetics, but none of these is likely to be limiting if conventional OPC cements are employed in repository construction. Nevertheless: Low-pH cements may supply approximately 50 % less hydroxyl ions than conventional OPC for a given volume of cement, but mass balance constraints are complicated by the uncertainty concerning the type of secondary minerals produced during cement-bentonite interaction. The change of aqueous

  7. pH during non-synaptic epileptiform activity—computational simulations

    Science.gov (United States)

    Márcio Rodrigues, Antônio; Canton Santos, Luiz Eduardo; Covolan, Luciene; Hamani, Clement; Guimarães de Almeida, Antônio-Carlos

    2015-10-01

    The excitability of neuronal networks is strongly modulated by changes in pH. The origin of these changes, however, is still under debate. The high complexity of neural systems justifies the use of computational simulation to investigate mechanisms that are possibly involved. Simulated neuronal activity includes non-synaptic epileptiform events (NEA) induced in hippocampal slices perfused with high-K+ and zero-Ca2+, therefore in the absence of the synaptic circuitry. A network of functional units composes the NEA model. Each functional unit represents one interface of neuronal/extracellular space/glial segments. Each interface contains transmembrane ionic transports, such as ionic channels, cotransporters, exchangers and pumps. Neuronal interconnections are mediated by gap-junctions, electric field effects and extracellular ionic fluctuations modulated by extracellular electrodiffusion. Mechanisms investigated are those that change intracellular and extracellular ionic concentrations and are able to affect [H+]. Our simulations suggest that the intense fluctuations in intra and extracellular concentrations of Na+, K+ and Cl- that accompany NEA are able to affect the combined action of the Na+/H+ exchanger (NHE), {{{HCO}}}3-/Cl- exchanger (HCE), H+ pump and the catalytic activity of intra and extracellular carbonic anhydrase. Cellular volume changes and extracellular electrodiffusion are responsible for modulating pH.

  8. The sigma-1 receptor modulates dopamine transporter conformation and cocaine binding and may thereby potentiate cocaine self-administration in rats.

    Science.gov (United States)

    Hong, Weimin Conrad; Yano, Hideaki; Hiranita, Takato; Chin, Frederick T; McCurdy, Christopher R; Su, Tsung-Ping; Amara, Susan G; Katz, Jonathan L

    2017-07-07

    The dopamine transporter (DAT) regulates dopamine (DA) neurotransmission by recapturing DA into the presynaptic terminals and is a principal target of the psychostimulant cocaine. The sigma-1 receptor (σ 1 R) is a molecular chaperone, and its ligands have been shown to modulate DA neuronal signaling, although their effects on DAT activity are unclear. Here, we report that the prototypical σ 1 R agonist (+)-pentazocine potentiated the dose response of cocaine self-administration in rats, consistent with the effects of the σR agonists PRE-084 and DTG (1,3-di- o -tolylguanidine) reported previously. These behavioral effects appeared to be correlated with functional changes of DAT. Preincubation with (+)-pentazocine or PRE-084 increased the B max values of [ 3 H]WIN35428 binding to DAT in rat striatal synaptosomes and transfected cells. A specific interaction between σ 1 R and DAT was detected by co-immunoprecipitation and bioluminescence resonance energy transfer assays. Mutational analyses indicated that the transmembrane domain of σ 1 R likely mediated this interaction. Furthermore, cysteine accessibility assays showed that σ 1 R agonist preincubation potentiated cocaine-induced changes in DAT conformation, which were blocked by the specific σ 1 R antagonist CM304. Moreover, σ 1 R ligands had distinct effects on σ 1 R multimerization. CM304 increased the proportion of multimeric σ 1 Rs, whereas (+)-pentazocine increased monomeric σ 1 Rs. Together these results support the hypothesis that σ 1 R agonists promote dissociation of σ 1 R multimers into monomers, which then interact with DAT to stabilize an outward-facing DAT conformation and enhance cocaine binding. We propose that this novel molecular mechanism underlies the behavioral potentiation of cocaine self-administration by σ 1 R agonists in animal models. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Plant Habitat (PH)

    Science.gov (United States)

    Onate, Bryan

    2016-01-01

    The International Space Station (ISS) will soon have a platform for conducting fundamental research of Large Plants. Plant Habitat (PH) is designed to be a fully controllable environment for high-quality plant physiological research. PH will control light quality, level, and timing, temperature, CO2, relative humidity, and irrigation, while scrubbing ethylene. Additional capabilities include leaf temperature and root zone moisture and oxygen sensing. The light cap will have red (630 nm), blue (450 nm), green (525 nm), far red (730 nm) and broad spectrum white LEDs. There will be several internal cameras (visible and IR) to monitor and record plant growth and operations.

  10. Modulation of transport properties of optimally doped La{sub 1.85}Sr{sub 0.15}CuO{sub 4} thin films via electric field modification of the grain boundaries

    Energy Technology Data Exchange (ETDEWEB)

    Hassan, Muhammad Umair [Center for Micro and Nano Devices, Department of Physics, COMSATS Institute of Information Technology, Islamabad (Pakistan); Cavendish Laboratory, Cambridge (United Kingdom); Wimbush, Stuart C. [The MacDiarmid Institute for Advanced Materials and Nanotechnology, Victoria University of Wellington (New Zealand)

    2015-09-15

    Modulation of the transport properties of a superconducting La{sub 1.85}Sr{sub 0.15}CuO{sub 4}-based ionic-liquid gated transistor has been achieved. For an applied gate bias V{sub g} ≥ 2 V, the characteristic sheet resistivity vs. temperature (R{sub s}-T) curves exhibit a fully reversible foot feature below the superconducting transition temperature (T{sub c}). In contrast to the behaviour expected from the large charge carrier density of this high-T{sub c} superconductor material, the normal state conductance above T{sub c} also exhibits a large modulation, indicating a larger charge screening length than that predicted from a simple Thomas-Fermi model. We regard these changes as due to electrostatic modification of the charge density at structural imperfections such as grain boundaries present within the sample. Such modification alters the coupling between superconducting domains and dictates the overall R{sub s}-T trend of the gated film. To explain our findings, we employ Mannhart's model of electronic band bending at the grain boundaries and propose that this band bending can be modulated by large electric fields resulting in the observed modulation of the transport properties of the device. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  11. Paratransit: An Instructional Module.

    Science.gov (United States)

    Scalici, Anthony

    A concept-based introduction to paratransit is provided in this instructional module for undergraduate and graduate transportation-related courses for disciplines such as engineering, business, marketing, and technology. The concept of paratransit generally refers to modes of transportation other than mass transit and solo-driven automobiles. The…

  12. Regulation of pH During Amelogenesis.

    Science.gov (United States)

    Lacruz, Rodrigo S; Nanci, Antonio; Kurtz, Ira; Wright, J Timothy; Paine, Michael L

    2010-02-01

    During amelogenesis, extracellular matrix proteins interact with growing hydroxyapatite crystals to create one of the most architecturally complex biological tissues. The process of enamel formation is a unique biomineralizing system characterized first by an increase in crystallite length during the secretory phase of amelogenesis, followed by a vast increase in crystallite width and thickness in the later maturation phase when organic complexes are enzymatically removed. Crystal growth is modulated by changes in the pH of the enamel microenvironment that is critical for proper enamel biomineralization. Whereas the genetic bases for most abnormal enamel phenotypes (amelogenesis imperfecta) are generally associated with mutations to enamel matrix specific genes, mutations to genes involved in pH regulation may result in severely affected enamel structure, highlighting the importance of pH regulation for normal enamel development. This review summarizes the intra- and extracellular mechanisms employed by the enamel-forming cells, ameloblasts, to maintain pH homeostasis and, also, discusses the enamel phenotypes associated with disruptions to genes involved in pH regulation.

  13. Extracellular pH Regulates Zinc Signaling via an Asp Residue of the Zinc-sensing Receptor (ZnR/GPR39)*

    Science.gov (United States)

    Cohen, Limor; Asraf, Hila; Sekler, Israel; Hershfinkel, Michal

    2012-01-01

    Zinc activates a specific Zn2+-sensing receptor, ZnR/GPR39, and thereby triggers cellular signaling leading to epithelial cell proliferation and survival. Epithelial cells that express ZnR, particularly colonocytes, face frequent changes in extracellular pH that are of physiological and pathological implication. Here we show that the ZnR/GPR39-dependent Ca2+ responses in HT29 colonocytes were maximal at pH 7.4 but were reduced by about 50% at pH 7.7 and by about 62% at pH 7.1 and were completely abolished at pH 6.5. Intracellular acidification did not attenuate ZnR/GPR39 activity, indicating that the pH sensor of this protein is located on an extracellular domain. ZnR/GPR39-dependent activation of extracellular-regulated kinase (ERK)1/2 or AKT pathways was abolished at acidic extracellular pH of 6.5. A similar inhibitory effect was monitored for the ZnR/GPR39-dependent up-regulation of Na+/H+ exchange activity at pH 6.5. Focusing on residues putatively facing the extracellular domain, we sought to identify the pH sensor of ZnR/GPR39. Replacing the histidine residues forming the Zn2+ binding site, His17 or His19, or other extracellular-facing histidines to alanine residues did not abolish the pH dependence of ZnR/GPR39. In contrast, replacing Asp313 with alanine resulted in similar Ca2+ responses triggered by ZnR/GPR39 at pH 7.4 or 6.5. This mutant also showed similar activation of ERK1/2 and AKT pathways, and ZnR-dependent up-regulation of Na+/H+ exchange at pH 7.4 and pH 6.5. Substitution of Asp313 to His or Glu residues restored pH sensitivity of the receptor. This indicates that Asp313, which was shown to modulate Zn2+ binding, is an essential residue of the pH sensor of GPR39. In conclusion, ZnR/GPR39 is tuned to sense physiologically relevant changes in extracellular pH that thus regulate ZnR-dependent signaling and ion transport activity. PMID:22879599

  14. Extracellular pH regulates zinc signaling via an Asp residue of the zinc-sensing receptor (ZnR/GPR39).

    Science.gov (United States)

    Cohen, Limor; Asraf, Hila; Sekler, Israel; Hershfinkel, Michal

    2012-09-28

    Zinc activates a specific Zn(2+)-sensing receptor, ZnR/GPR39, and thereby triggers cellular signaling leading to epithelial cell proliferation and survival. Epithelial cells that express ZnR, particularly colonocytes, face frequent changes in extracellular pH that are of physiological and pathological implication. Here we show that the ZnR/GPR39-dependent Ca(2+) responses in HT29 colonocytes were maximal at pH 7.4 but were reduced by about 50% at pH 7.7 and by about 62% at pH 7.1 and were completely abolished at pH 6.5. Intracellular acidification did not attenuate ZnR/GPR39 activity, indicating that the pH sensor of this protein is located on an extracellular domain. ZnR/GPR39-dependent activation of extracellular-regulated kinase (ERK)1/2 or AKT pathways was abolished at acidic extracellular pH of 6.5. A similar inhibitory effect was monitored for the ZnR/GPR39-dependent up-regulation of Na(+)/H(+) exchange activity at pH 6.5. Focusing on residues putatively facing the extracellular domain, we sought to identify the pH sensor of ZnR/GPR39. Replacing the histidine residues forming the Zn(2+) binding site, His(17) or His(19), or other extracellular-facing histidines to alanine residues did not abolish the pH dependence of ZnR/GPR39. In contrast, replacing Asp(313) with alanine resulted in similar Ca(2+) responses triggered by ZnR/GPR39 at pH 7.4 or 6.5. This mutant also showed similar activation of ERK1/2 and AKT pathways, and ZnR-dependent up-regulation of Na(+)/H(+) exchange at pH 7.4 and pH 6.5. Substitution of Asp(313) to His or Glu residues restored pH sensitivity of the receptor. This indicates that Asp(313), which was shown to modulate Zn(2+) binding, is an essential residue of the pH sensor of GPR39. In conclusion, ZnR/GPR39 is tuned to sense physiologically relevant changes in extracellular pH that thus regulate ZnR-dependent signaling and ion transport activity.

  15. The mechanism by which a propeptide-encoded pH sensor regulates spatiotemporal activation of furin.

    Science.gov (United States)

    Williamson, Danielle M; Elferich, Johannes; Ramakrishnan, Parvathy; Thomas, Gary; Shinde, Ujwal

    2013-06-28

    The proprotein convertase furin requires the pH gradient of the secretory pathway to regulate its multistep, compartment-specific autocatalytic activation. Although His-69 within the furin prodomain serves as the pH sensor that detects transport of the propeptide-enzyme complex to the trans-Golgi network, where it promotes cleavage and release of the inhibitory propeptide, a mechanistic understanding of how His-69 protonation mediates furin activation remains unclear. Here we employ biophysical, biochemical, and computational approaches to elucidate the mechanism underlying the pH-dependent activation of furin. Structural analyses and binding experiments comparing the wild-type furin propeptide with a nonprotonatable His-69 → Leu mutant that blocks furin activation in vivo revealed protonation of His-69 reduces both the thermodynamic stability of the propeptide as well as its affinity for furin at pH 6.0. Structural modeling combined with mathematical modeling and molecular dynamic simulations suggested that His-69 does not directly contribute to the propeptide-enzyme interface but, rather, triggers movement of a loop region in the propeptide that modulates access to the cleavage site and, thus, allows for the tight pH regulation of furin activation. Our work establishes a mechanism by which His-69 functions as a pH sensor that regulates compartment-specific furin activation and provides insights into how other convertases and proteases may regulate their precise spatiotemporal activation.

  16. The Mechanism by Which a Propeptide-encoded pH Sensor Regulates Spatiotemporal Activation of Furin*

    Science.gov (United States)

    Williamson, Danielle M.; Elferich, Johannes; Ramakrishnan, Parvathy; Thomas, Gary; Shinde, Ujwal

    2013-01-01

    The proprotein convertase furin requires the pH gradient of the secretory pathway to regulate its multistep, compartment-specific autocatalytic activation. Although His-69 within the furin prodomain serves as the pH sensor that detects transport of the propeptide-enzyme complex to the trans-Golgi network, where it promotes cleavage and release of the inhibitory propeptide, a mechanistic understanding of how His-69 protonation mediates furin activation remains unclear. Here we employ biophysical, biochemical, and computational approaches to elucidate the mechanism underlying the pH-dependent activation of furin. Structural analyses and binding experiments comparing the wild-type furin propeptide with a nonprotonatable His-69 → Leu mutant that blocks furin activation in vivo revealed protonation of His-69 reduces both the thermodynamic stability of the propeptide as well as its affinity for furin at pH 6.0. Structural modeling combined with mathematical modeling and molecular dynamic simulations suggested that His-69 does not directly contribute to the propeptide-enzyme interface but, rather, triggers movement of a loop region in the propeptide that modulates access to the cleavage site and, thus, allows for the tight pH regulation of furin activation. Our work establishes a mechanism by which His-69 functions as a pH sensor that regulates compartment-specific furin activation and provides insights into how other convertases and proteases may regulate their precise spatiotemporal activation. PMID:23653353

  17. pH Sensing and Regulation in Cancer

    OpenAIRE

    Mehdi eDamaghi; Jonathan W. Wojtkowiak; Robert J. Gillies

    2013-01-01

    Cells maintain intracellular pH (pHi) within a narrow range (7.1-7.2) by controlling membrane proton pumps and transporters whose activity is set by intra-cytoplasmic pH sensors. These sensors have the ability to recognize and induce cellular responses to maintain the intracellular pH, often at the expense of acidifying the extracellular pH. In turn, extracellular acidification impacts cells via specific acid-sensing ion channels (ASICs) and proton-sensing G-protein coupled receptors (GPCRs...

  18. Electrical transport through Pb(Zr,Ti)O3 p-n and p-p heterostructures modulated by bound charges at a ferroelectric surface: Ferroelectric p-n diode

    Science.gov (United States)

    Watanabe, Yukio

    1999-05-01

    Current through (Pb,La)(Zr,Ti)O3 ferroelectrics on perovskite semiconductors is found to exhibit diode characteristics of which polarity is universally determined by the carrier conduction-type semiconductors. A persisting highly reproducible resistance modulation by a dc voltage, which has a short retention, is observed and is ascribed to a band bending of the ferroelectric by the formation of charged traps. This interpretation is consistent with a large relaxation current observed at a low voltage. On the other hand, a reproducible resistance modulation by a pulse voltage, which has a long retention, is observed in metal/(Pb,La)(Zr,Ti)O3/SrTiO3:Nb but not in metal/(Pb,La)(Zr,Ti)O3/(La,Sr)2CuO4 and is attributed to a possible band bending due to the spontaneous polarization (P) switching. The observed current voltage (IV) characteristics, the polarity dependence, the relaxation, and the modulation are explicable, if we assume a p-n or a p-p junction at the ferroelectric semiconductor interface (p: hole conduction type, n: electron conduction type). The analysis suggests that an intrinsically inhomogeneous P (∇P) near the ferroelectric/metal interface is likely very weak or existing in a very thin layer, when a reaction of the metal with the ferroelectric is eliminated. Additionally, the various aspects of transport through ferroelectrics are explained as a transport in the carrier depleted region.

  19. Photovoltaic module and interlocked stack of photovoltaic modules

    Science.gov (United States)

    Wares, Brian S.

    2012-09-04

    One embodiment relates to an arrangement of photovoltaic modules configured for transportation. The arrangement includes a plurality of photovoltaic modules, each photovoltaic module including a frame having at least a top member and a bottom member. A plurality of alignment features are included on the top member of each frame, and a plurality of alignment features are included on the bottom member of each frame. Adjacent photovoltaic modules are interlocked by the alignment features on the top member of a lower module fitting together with the alignment features on the bottom member of an upper module. Other embodiments, features and aspects are also disclosed.

  20. Endomembrane Cation Transporters and Membrane Trafficking

    Energy Technology Data Exchange (ETDEWEB)

    Sze, Heven [Univ. of Maryland, College Park, MD (United States). Dept. of Cell Biology & Molecular Genetics

    2017-04-01

    Multicellular, as well as unicellular, organisms have evolved mechanisms to regulate ion and pH homeostasis in response to developmental cues and to a changing environment. The working hypothesis is that the balance of fluxes mediated by diverse transporters at the plasma membrane and in subcellular organelles determines ionic cellular distribution, which is critical for maintenance of membrane potential, pH control, osmolality, transport of nutrients, and protein activity. An emerging theme in plant cell biology is that cells respond and adapt to diverse cues through changes of the dynamic endomembrane system. Yet we know very little about the transporters that might influence the operation of the secretory system in plants. Here we focus on transporters that influence alkali cation and pH homeostasis, mainly in the endomembrane/ secretory system. The endomembrane system of eukaryote cells serves several major functions: i) sort cargo (e.g. enzymes, transporters or receptors) to specific destinations, ii) modulate the protein and lipid composition of membrane domains through remodeling, and iii) determine and alter the properties of the cell wall through synthesis and remodeling. We had uncovered a novel family of predicted cation/H+ exchangers (CHX) and K+ efflux antiporters (KEA) that are prevalent in higher plants, but rare in metazoans. We combined phylogenetic and transcriptomic analyses with molecular genetic, cell biological and biochemical studies, and have published the first reports on functions of plant CHXs and KEAs. CHX studied to date act at the endomembrane system where their actions are distinct from the better-studied NHX (Na/K-H+ exchangers). Arabidopsis thaliana CHX20 in guard cells modulate stomatal opening, and thus is significant for vegetative survival. Other CHXs ensure reproductive success on dry land, as they participate in organizing pollen walls, targeting of pollen tubes to the ovule or promoting

  1. Numerical modelling of near-bottom sediment transport: turbulence modulation, new process models and application to the Scheldt and the Belgian coast

    OpenAIRE

    Bi, Q.

    2015-01-01

    Sediment transport due to fluid motion is a crucial process in many environmental and engineered systems. Therefore, understanding sediment transport is critical for predicting sediment movements and evaluating the short and/or long-term influence to the surface water systems. Despite the importance of sediment transport, the fundamental aspects involved are far from being completely understood. At the core of the problem is the complex interaction between a turbulent flow field and sediment ...

  2. PhD Dissertations

    OpenAIRE

    Redazione Reti Medievali (a cura di)

    2010-01-01

    Report of PhD Dissertations.Anna Airò La scrittura delle regole. Politica e istituzioni a Taranto nel Quattrocento, Tesi di dottorato di ricerca in Storia medievale, Università degli studi di Firenze, 2005 Pasquale Arfé La Clavis Physicae II (316-529) di Honorius Augustodunensis. Studio ed edizione critica, Tesi di dottorato in Storia della filosofia medievale, Università degli Studi di Napoli "L'Orientale", 2005 Alessandro Azzimonti Scrittura agiografica e strutture di potere nell'Italia c...

  3. Influence of solution pH on the electron transport of the self-assembled nanoarrays of single-walled carbon nanotube-cobalt tetra-aminophthalocyanine on gold electrodes: Electrocatalytic detection of epinephrine

    Energy Technology Data Exchange (ETDEWEB)

    Ozoemena, Kenneth I. [Chemistry Department, University of Pretoria, Pretoria 0002 (South Africa)], E-mail: kenneth.ozoemena@up.ac.za; Nkosi, Dudu; Pillay, Jeseelan [Chemistry Department, University of Pretoria, Pretoria 0002 (South Africa)

    2008-02-15

    This paper provides first evidence of the impact of solution pH on the heterogeneous electron transfer rate constants of self-assembled films of single-walled carbon nanotubes (SWCNT) and SWCNT integrated to cobalt(II)tetra-aminophthalocyanine (SWCNT-CoTAPc) by sequential self-assembly. Using cyclic voltammetry and electrochemical impedance spectroscopy, we proved that both SAMs exhibit notable differences in their response to different buffered solution pH, with and without the presence of redox probe, [Fe(CN){sub 6}]{sup 4-}/[Fe(CN){sub 6}]{sup 3-}. Surface pK{sub a} value for the Au-Cys-SWCNT-CoTAPc was estimated as ca. 7.8, compared to that of the Au-Cys-SWCNT of about 5.5. Interestingly, both redox-active SAMs gave similar analytical response for epinephrine, giving well-resolved square wave voltammograms, with linear concentration range up to 130 {mu}M, sensitivity of ca. 9.4 x 10{sup -3} AM{sup -1}, and limit of detection ca. 6 {mu}M. This analytical result implies that there is no detectable advantage of one of the SAMs over the other in the electrocatalytic detection of this neurotransmitter.

  4. Esophageal pH monitoring

    Science.gov (United States)

    pH monitoring - esophageal; Esophageal acidity test ... Esophageal pH monitoring is used to check how much stomach acid is entering the esophagus. It also checks how well the acid is cleared downward into the ...

  5. Characterization of inorganic phosphate transport in the triple-negative breast cancer cell line, MDA-MB-231.

    Science.gov (United States)

    Russo-Abrahão, Thais; Lacerda-Abreu, Marco Antônio; Gomes, Tainá; Cosentino-Gomes, Daniela; Carvalho-de-Araújo, Ayra Diandra; Rodrigues, Mariana Figueiredo; Oliveira, Ana Carolina Leal de; Rumjanek, Franklin David; Monteiro, Robson de Queiroz; Meyer-Fernandes, José Roberto

    2018-01-01

    Recent studies demonstrate that interstitial inorganic phosphate is significantly elevated in the breast cancer microenvironment as compared to normal tissue. In addition it has been shown that breast cancer cells express high levels of the NaPi-IIb carrier (SLC34A2), suggesting that this carrier may play a role in breast cancer progression. However, the biochemical behavior of inorganic phosphate (Pi) transporter in this cancer type remains elusive. In this work, we characterize the kinetic parameters of Pi transport in the aggressive human breast cancer cell line, MDA-MB-231, and correlated Pi transport with cell migration and adhesion. We determined the influence of sodium concentration, pH, metabolic inhibitors, as well as the affinity for inorganic phosphate in Pi transport. We observed that the inorganic phosphate is dependent on sodium transport (K0,5 value = 21.98 mM for NaCl). Furthermore, the transport is modulated by different pH values and increasing concentrations of Pi, following the Michaelis-Menten kinetics (K0,5 = 0.08 mM Pi). PFA, monensin, furosemide and ouabain inhibited Pi transport, cell migration and adhesion. Taken together, these results showed that the uptake of Pi in MDA-MB-231 cells is modulated by sodium and by regulatory mechanisms of intracellular sodium gradient. General Significance: Pi transport might be regarded as a potential target for therapy against tumor progression.

  6. Transport and Sustainability

    DEFF Research Database (Denmark)

    Jørgensen, Kaj

    1997-01-01

    Ph.D. study of the scope for sustainable transport in Denmark, and particularly of the role of the motor vehicle in this context. The distribution of groceries is used as case study of the introduction of the motor vehicle in Denmark, concluding that this has resulted in increases of the transport...

  7. Modulation of the partition coefficient between octanol and buffer at pH 7.4 and pKa to achieve the optimum balance of blood clearance and volume of distribution for a series of tetrahydropyran histamine type 3 receptor antagonists.

    Science.gov (United States)

    Hay, Tanya; Jones, Rhys; Beaumont, Kevin; Kemp, Mark

    2009-09-01

    The relationship between rat pharmacokinetics and physicochemical parameters [the partition coefficient between octanol and buffer at pH 7.4 (log D((7.4))) and pK(a)] was studied for a series of tetrahydropyran compounds. Sixteen compounds ranging in log D((7.4)) 0.1 to 1.8 were administered intravenously to rats, and the pharmacokinetic parameters were determined from blood concentration time curves. Across the series, a weak correlation was observed between log D((7.4)) and blood clearance, suggesting that log D((7.4)) values less than 0.5 were required to prevent clearance at hepatic blood flow. In terms of the volume of distribution (V(d)), the compounds fell into three distinct subseries characterized by the number of basic centers and differences in ionization of each basic center at physiological pH. These were referred to as the monobasic, weak second base, and strong second base subseries. All the compounds exhibited V(d) greater than body water, as would be expected from their lipophilic and basic nature. For a given clog P, the strong second base subseries showed higher V(d) than the weak second base subseries, which in turn exhibited higher values than the monobasic subseries. In addition, for the weak second base subseries, V(d) could be tuned by modulating the pK(a) of the second basic center. This relationship was rationalized in respect to the interactions of the ionizable centers with phospholipid heads in the cell membrane and/or lysosomal trapping. Compounds in the weak second base subseries showed optimal V(d), and when combined with a log D((7.4)) of 0.1, driving to moderate blood clearance, one compound showed the optimal pharmacokinetic profile.

  8. Myricetin stimulates the absorption of the pro-carcinogen PhIP

    NARCIS (Netherlands)

    Schutte, M.E.; Sandt, J.J.M. van de; Alink, G.M.; Groten, J.P.; Rietjens, I.M.C.M.

    2006-01-01

    The effect of the flavonoid myricetin on the transport of the pro-carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through differentiated Caco-2 monolayers, a model for the intestinal epithelium, is described. Myricetin causes an increase of the transport of PhIP from the apical to

  9. Transport Statistics - Transport - UNECE

    Science.gov (United States)

    Sustainable Energy Statistics Trade Transport Themes UNECE and the SDGs Climate Change Gender Ideas 4 Change UNECE Weekly Videos UNECE Transport Areas of Work Transport Statistics Transport Transport Statistics About us Terms of Reference Meetings and Events Meetings Working Party on Transport Statistics (WP.6

  10. PhD Dissertations

    Directory of Open Access Journals (Sweden)

    Redazione Reti Medievali (a cura di

    2004-06-01

    Full Text Available Report of PhD Dissertations. Francesco Barone Istituzioni, società ed economia a Catania nel tardo medioevo (XIV-XV secolo, Tesi di dottorato in Storia medievale (XVI ciclo, Università degli Studi di Firenze, 2004   Laura Berti Ceroni Il territorio e le strutture di Cesarea e Classe tra tarda antichità e alto medioevo in rapporto con Ravenna, Tesi di dottorato di ricerca in Storia e Informatica, Università degli studi di Bologna, 2002-2003.   Marco Bicchierai Poppi dalla signoria dei conti Guidi al vicariato del Casentino (1360-1480, Tesi di dottorato in Storia medievale (XIV ciclo, Università degli Studi di Firenze, 2004   Emanuela Garimberti Spatiosa ad habitandum loca. Luoghi e identità nella Historia Langobardorum di Paolo Diacono, Tesi di dottorato in Storia medievale (XV ciclo, Università degli Studi di Bologna, 2004   Lorenzo Tanzini Sistemi normativi e pratiche istituzionali a Firenze dalla fine del XIII all’inizio del XV secolo, Tesi di dottorato di ricerca in Storia medievale (XVI ciclo, Università degli Studi di Firenze, 2004   Stefania Tarquini Pellegrinaggio e asseto urbano di Roma, Tesi di dottorato di ricerca in Storia dei centri, delle vie e della cultura dei pellegrinaggi nel Medioevo euro mediterraneo (XV ciclo, Università degli studi di Lecce, 2003

  11. PhD Dissertations

    Directory of Open Access Journals (Sweden)

    Redazione Reti Medievali (a cura di

    2010-06-01

    Full Text Available Report of PhD dissertations. Andrea Brugnoli Una storia locale: l’organizzazione del territorio veronese nel medioevo: trasformazioni della realtà e schemi notarili (IX-metà XII secolo, Tesi di dottorato di ricerca in Scienze Storiche e Antropologiche (XXII ciclo, Università degli Studi di Verona, 2010   Luca Filangieri Famiglie e gruppi dirigenti a Genova (secoli XII-metà XIII, Tesi di dottorato di ricerca in Storia medievale (XXII ciclo, Università degli Studi di Firenze, 2010   Jakub Kujawi ski Wernakularna kolekcja historiograficzna z rękopisu francuskiego nr 688 z Biblioteki Narodowej w Paryżu. Studium źródłoznawcze (La raccolta dei volgarizzamenti delle opere storiografiche nel manoscritto francese 688 della Biblioteca Nazionale di Parigi, Tesi di dottorato, Università “Adam Mickiewicz”, Facoltà di Storia, Pozna, a.a. 2009/2010   Marta Longhi I signori “de Radicata”. Strategie di affermazione familiare e patrimoniale nel Piemonte dei secoli XII-XIV, Tesi di dottorato di ricerca in Istituzioni, Società, Religioni dal Tardo Antico alla fine del Medioevo (XX ciclo, Università di Torino, 2008

  12. PhD Dissertations

    Directory of Open Access Journals (Sweden)

    Redazione Reti Medievali (a cura di

    2003-06-01

    Full Text Available Reporto of PhD Dissertations.   Mario Dalle Carbonare Società, potere e clientele nell’Irlanda altomedievale (secoli V-IX, Tesi di dottorato di ricerca in Storia sociale europea, Università "Ca' Foscari" di Venezia, 2003 Vieri Mazzoni La legislazione antighibellina e la politica oligarchica della Parte Guelfa di Firenze nel secondo Trecento (1347-1378, Tesi di dottorato di ricerca in Storia Medievale (ciclo XII, Università degli Studi di Firenze   Alma Poloni Pisa dalle origini del movimento popolare alla discesa di Ludovico il Bavaro. I gruppi dirigenti cittadini tra continuità e trasformazione, Tesi di dottorato di ricerca in Storia dell'Europa nel medioevo, Università degli studi di Pisa, 2003   Andrea Puglia Potere marchionale, amministrazione del territorio, società locali dalla morte di Ugo di Tuscia a Guelfo VI di Baviera (1001-1160, Tesi di dottorato di ricerca in Storia medievale, Università degli studi di Milano, 2003

  13. Interfacial reactions in thermoelectric modules

    KAUST Repository

    Wu, Hsin-jay; Wu, Albert T.; Wei, Pei-chun; Chen, Sinn-wen

    2018-01-01

    Engineering transport properties of thermoelectric (TE) materials leads to incessantly breakthroughs in the zT values. Nevertheless, modular design holds a key factor to advance the TE technology. Herein, we discuss the structures of TE module

  14. Intracellular pH gradients in migrating cells

    DEFF Research Database (Denmark)

    Martin, Christine; Pedersen, Stine Helene Falsig; Schwab, Albrecht

    2011-01-01

    might function as such unevenly distributed regulators as they modulate the interaction of focal adhesion proteins and components of the cytoskeleton in vitro. However, an intracellular pH (pH(i)) gradient reflecting a spatial asymmetry of protons has not been shown so far. One major regulator of p...

  15. Demonstration of high mobility and quantum transport in modulation-doped β-(AlxGa1-x)2O3/Ga2O3 heterostructures

    Science.gov (United States)

    Zhang, Yuewei; Neal, Adam; Xia, Zhanbo; Joishi, Chandan; Johnson, Jared M.; Zheng, Yuanhua; Bajaj, Sanyam; Brenner, Mark; Dorsey, Donald; Chabak, Kelson; Jessen, Gregg; Hwang, Jinwoo; Mou, Shin; Heremans, Joseph P.; Rajan, Siddharth

    2018-04-01

    In this work, we demonstrate a high mobility two-dimensional electron gas (2DEG) formed at the β-(AlxGa1-x)2O3/Ga2O3 interface through modulation doping. Shubnikov-de Haas (SdH) oscillations were observed in the modulation-doped β-(AlxGa1-x)2O3/Ga2O3 structure, indicating a high-quality electron channel formed at the heterojunction interface. The formation of the 2DEG channel was further confirmed by the weak temperature dependence of the carrier density, and the peak low temperature mobility was found to be 2790 cm2/Vs, which is significantly higher than that achieved in bulk-doped Beta-phase Gallium Oxide (β-Ga2O3). The observed SdH oscillations allowed for the extraction of the electron effective mass in the (010) plane to be 0.313 ± 0.015 m0 and the quantum scattering time to be 0.33 ps at 3.5 K. The demonstrated modulation-doped β-(AlxGa1-x)2O3/Ga2O3 structure lays the foundation for future exploration of quantum physical phenomena and semiconductor device technologies based on the β-Ga2O3 material system.

  16. Long-range atmospheric transport of persistent organic pollutants, I: description of surface-atmosphere exchange modules and implementation in EUROS.

    NARCIS (Netherlands)

    Jacobs, C.M.J.; Pul, van W.A.J.

    1996-01-01

    Concerns a description of a model for the exchange of gaseous Persistent Organic Pollutants (POP) at land and sea surfaces and its application in the Eulerian air pollution transport model EUROS. Sample simulations of the net deposition of lindane over Europe are discussed. For non-emission areas

  17. Implications for metal and volatile cycles from the pH of subduction zone fluids

    Science.gov (United States)

    Galvez, Matthieu E.; Connolly, James A. D.; Manning, Craig E.

    2016-11-01

    The chemistry of aqueous fluids controls the transport and exchange—the cycles—of metals and volatile elements on Earth. Subduction zones, where oceanic plates sink into the Earth’s interior, are the most important geodynamic setting for this fluid-mediated chemical exchange. Characterizing the ionic speciation and pH of fluids equilibrated with rocks at subduction zone conditions has long been a major challenge in Earth science. Here we report thermodynamic predictions of fluid-rock equilibria that tie together models of the thermal structure, mineralogy and fluid speciation of subduction zones. We find that the pH of fluids in subducted crustal lithologies is confined to a mildly alkaline range, modulated by rock volatile and chlorine contents. Cold subduction typical of the Phanerozoic eon favours the preservation of oxidized carbon in subducting slabs. In contrast, the pH of mantle wedge fluids is very sensitive to minor variations in rock composition. These variations may be caused by intramantle differentiation, or by infiltration of fluids enriched in alkali components extracted from the subducted crust. The sensitivity of pH to soluble elements in low abundance in the host rocks, such as carbon, alkali metals and halogens, illustrates a feedback between the chemistry of the Earth’s atmosphere-ocean system and the speciation of subduction zone fluids via the composition of the seawater-altered oceanic lithosphere. Our findings provide a perspective on the controlling reactions that have coupled metal and volatile cycles in subduction zones for more than 3 billion years7.

  18. A PhD is a PhD is a PhD

    OpenAIRE

    Ostrow, Deborah Anne

    2017-01-01

    A PhD is a PhD is a PhD is a practice-based project that interrogates the process of an artist undertaking PhD research under established criteria. It consists of an exegesis, an original screenplay, and a digital film made for online viewing, with images drawn from a range of documentaries and films found on YouTube. They have been dissected, re-assembled and then re-embedded to YouTube. The source material covers topics such as medicalization of madness, the conspicuous appropriation of uni...

  19. L-Theanine Administration Modulates the Absorption of Dietary Nutrients and Expression of Transporters and Receptors in the Intestinal Mucosa of Rats

    Directory of Open Access Journals (Sweden)

    Qiongxian Yan

    2017-01-01

    Full Text Available L-theanine has various advantageous functions for human health; whether or not it could mediate the nutrients absorption is unknown yet. The effects of L-theanine on intestinal nutrients absorption were investigated using rats ingesting L-theanine solution (0, 50, 200, and 400 mg/kg body weight per day for two weeks. The decline of insulin secretion and glucose concentration in the serum was observed by L-theanine. Urea and high-density lipoprotein were also reduced by 50 mg/kg L-theanine. Jejunal and ileac basic amino acids transporters SLC7a1 and SLC7a9, neutral SLC1a5 and SLC16a10, and acidic SLC1a1 expression were upregulated. The expression of intestinal SGLT3 and GLUT5 responsible for carbohydrates uptake and GPR120 and FABP2 associated with fatty acids transport were inhibited. These results indicated that L-theanine could inhibit the glucose uptake by downregulating the related gene expression in the small intestine of rats. Intestinal gene expression of transporters responding to amino acids absorption was stimulated by L-theanine administration.

  20. A Case Study On the Relative Influence of Free Tropospheric Subsidence, Long Range Transport and Local Production in Modulating Ozone Concentrations over Qatar

    Science.gov (United States)

    Ayoub, Mohammed; Ackermann, Luis; Fountoukis, Christos; Gladich, Ivan

    2016-04-01

    The Qatar Environment and Energy Research Institute (QEERI) operates a network of air quality monitoring stations (AQMS) around the Doha metropolitan area and an ozonesonde station with regular weekly launches and occasional higher frequency launch experiments (HFLE). Six ozonesondes were launched at 0700 LT/0400 UTC and 1300 LT/1000 UTC over a three day period between 10-12 September, 2013. We present the analysis of the ozonesonde data coupled with regional chemical transport modeling over the same time period using WRF-Chem validated against both the ozonesonde and surface AQMS measurements. The HFLE and modeling show evidence of both subsidence and transboundary transport of ozone during the study period, coupled with a strong sea breeze circulation on the 11th of September resulting in elevated ozone concentrations throughout the boundary layer. The development of the sea breeze during the course of the day and influence of the early morning residual layer versus daytime production is quantified. The almost complete titration of ozone in the morning hours of 11 September, 2013 is attributed to local vehicular emissions of NOx and stable atmospheric conditions prevailing over the Doha area. The relative contribution of long range transport of ozone along the Arabian Gulf coast and local urban emissions are discussed.

  1. The pH Game.

    Science.gov (United States)

    Chemecology, 1996

    1996-01-01

    Describes a game that can be used to teach students about the acidity of liquids and substances around their school and enable them to understand what pH levels tell us about the environment. Students collect samples and measure the pH of water, soil, plants, and other natural material. (DDR)

  2. Analysis of carrier transport and carrier trapping in organic diodes with polyimide-6,13-Bis(triisopropylsilylethynyl)pentacene double-layer by charge modulation spectroscopy and optical second harmonic generation measurement

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Eunju, E-mail: elim@dankook.ac.kr, E-mail: taguchi.d.aa@m.titech.ac.jp, E-mail: iwamoto@pe.titech.ac.jp [Department of Applied Physics, Institute of Nanosensor and Biotechnology, Dankook University, Jukjeon-dong, Gyeonggi-do 448-701 (Korea, Republic of); Taguchi, Dai, E-mail: elim@dankook.ac.kr, E-mail: taguchi.d.aa@m.titech.ac.jp, E-mail: iwamoto@pe.titech.ac.jp; Iwamoto, Mitsumasa, E-mail: elim@dankook.ac.kr, E-mail: taguchi.d.aa@m.titech.ac.jp, E-mail: iwamoto@pe.titech.ac.jp [Department of Physical Electronics, Tokyo Institute of Technology 2-12-1, O-okayama, Meguro-ku, Tokyo 152-8552 (Japan)

    2014-08-18

    We studied the carrier transport and carrier trapping in indium tin oxide/polyimide (PI)/6,13-Bis(triisopropylsilylethynyl)pentacene (TIPS-pentacene)/Au diodes by using charge modulation spectroscopy (CMS) and time-resolved electric field induced optical second harmonic generation (TR-EFISHG) measurements. TR-EFISHG directly probes the spatial carrier behaviors in the diodes, and CMS is useful in explaining the carrier motion with respect to energy. The results clearly indicate that the injected carriers move across TIPS-pentacene thorough the molecular energy states of TIPS-pentacene and accumulate at the PI/TIPS-pentacene interface. However, some carriers are trapped in the PI layers. These findings take into account the capacitance-voltage and current-voltage characteristics of the diodes.

  3. Market Segmentation: An Instructional Module.

    Science.gov (United States)

    Wright, Peter H.

    A concept-based introduction to market segmentation is provided in this instructional module for undergraduate and graduate transportation-related courses. The material can be used in many disciplines including engineering, business, marketing, and technology. The concept of market segmentation is primarily a transportation planning technique by…

  4. Human vaginal pH and microbiota: an update.

    Science.gov (United States)

    Godha, Keshav; Tucker, Kelly M; Biehl, Colton; Archer, David F; Mirkin, Sebastian

    2018-06-01

    A woman's vaginal pH has many implications on her health and it can be a useful tool in disease diagnosis and prevention. For that reason, the further examination of the relationship between the human vaginal pH and microbiota is imperative. In the past several decades, much has been learned about the physiological mechanisms modulating the vaginal pH, and exogenous/genetic factors that may influence it. A unified, coherent understanding of these concepts is presented to comprehend their interrelationships and their cumulative effect on a woman's health. In this review, we explore research on vaginal pH and microbiota throughout a woman's life, vaginal intermediate cell anaerobic metabolism and net proton secretion by the vaginal epithelial, and the way these factors interact to acidify the vaginal pH. This review provides foundational information about what a microbiota is and its relationship with human physiology and vaginal pH. We then evaluate the influence of physiological mechanisms, demographic factors, and propose ideas for the mechanisms behind their action on the vaginal pH.

  5. Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats.

    Science.gov (United States)

    Alasmari, Fawaz; Bell, Richard L; Rao, P S S; Hammad, Alaa M; Sari, Youssef

    2018-07-01

    Impairment in glutamate neurotransmission mediates the development of dependence upon nicotine (NIC) and ethanol (EtOH). Previous work indicates that continuous access to EtOH or phasic exposure to NIC reduces expression of the glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT) but not the glutamate/aspartate transporter (GLAST). Additionally, metabotropic glutamate receptors (mGluRs) expression was affected following exposure to EtOH or NIC. However, little is known about the effects of EtOH and NIC co-consumption on GLT-1, xCT, GLAST, and mGluR1 expression. In this study, peri-adolescent female alcohol preferring (P) rats were given binge-like access to water, sucrose (SUC), SUC-NIC, EtOH, or EtOH-NIC for four weeks. The present study determined the effects of these reinforcers on GLT-1, xCT, GLAST, and mGluR1 expression in the nucleus accumbens (NAc), hippocampus (HIP) and prefrontal cortex (PFC). GLT-1 and xCT expression were decreased in the NAc following both SUC-NIC and EtOH-NIC. In addition, only xCT expression was downregulated in the HIP in both of these latter groups. Also, glutathione peroxidase (GPx) activity in the HIP was reduced following SUC, SUC-NIC, EtOH, and EtOH-NIC consumption. Similar to previous work, GLAST expression was not altered in any brain region by any of the reinforcers. However, mGluR1 expression was increased in the NAc in the SUC-NIC, EtOH, and EtOH-NIC groups. These results indicate that peri-adolescent binge-like drinking of EtOH or SUC with or without NIC may exert differential effects on astroglial glutamate transporters and receptors. Our data further parallel some of the previous findings observed in adult rats. Copyright © 2018. Published by Elsevier Inc.

  6. Effect of pH on Pulp Potential and Sulphide Mineral Flotation

    OpenAIRE

    GÖKTEPE, Ferihan

    2014-01-01

    Control of pH is one of the most widely applied methods for the modulation of mineral flotation. In this study the effect of pH on potential in solution and sulphur minerals flotation is discussed with various electrodes. The electrodes were platinum, gold, chalcopyrite, pyrite and galena. In solution, potentials were linearly dependent on pH with a different slope for each electrode. Chalcopyrite, pyrite, sphalerite and galena minerals flotation tests were performed in a microflot...

  7. 3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: β-ketoamphetamine modulation of neurotoxicity by the dopamine transporter

    Science.gov (United States)

    Anneken, John H.; Angoa-Pérez, Mariana; Kuhn, Donald M.

    2016-01-01

    Methylone, 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone are psychoactive ingredients of ‘bath salts’ and their abuse represents a growing public health care concern. These drugs are cathinone derivatives and are classified chemically as β-ketoamphetamines. Because of their close structural similarity to the amphetamines, methylone, MDPV, and mephedrone share most of their pharmacological, neurochemical, and behavioral properties. One point of divergence in their actions is the ability to cause damage to the CNS. Unlike methamphetamine, the β-ketoamphetamines do not damage dopamine (DA) nerve endings. However, mephedrone has been shown to significantly accentuate methamphetamine neurotoxicity. Bath salt formulations contain numerous different psychoactive ingredients, and individuals who abuse bath salts also coabuse other illicit drugs. Therefore, we have evaluated the effects of methylone, MDPV, mephedrone, and methamphetamine on DA nerve endings. The β-ketoamphetamines alone or in all possible two-drug combinations do not result in damage to DA nerve endings but do cause hyperthermia. MDPV completely protects against the neurotoxic effects of methamphetamine while methylone accentuates it. Neither MDPV nor methylone attenuates the hyperthermic effects of methamphetamine. The potent neuroprotective effects of MDPV extend to amphetamine-, 3,4-methylenedioxymethamphetamine-, and MPTP-induced neurotoxicity. These results indicate that β-ketoamphetamine drugs that are non-substrate blockers of the DA transporter (i.e., MDPV) protect against methamphetamine neurotoxicity, whereas those that are substrates for uptake by the DA transporter and which cause DA release (i.e., methylone, mephedrone) accentuate neurotoxicity. PMID:25626880

  8. Plasma transport studies using transient techniques

    International Nuclear Information System (INIS)

    Simonen, T.C.; Brower, D.L.; Efthimion, P.

    1991-01-01

    Selected topics from the Transient Transport sessions of the Transport Task Force Workshop, held February 19-23, 1990, in Hilton Head, South Carolina are summarized. Presentations on sawtooth propagation, ECH modulation, particle modulation, and H-mode transitions are included. The research results presented indicated a growing theoretical understanding and experimental sophistication in the application of transient techniques to transport studies. (Author)

  9. Urine pH test

    Science.gov (United States)

    ... urine test Male urinary tract References Bose A, Monk RD, Bushinsky DA. Kidney stones. In: Melmed S, Polonsky ... and its influence on urine pH. J Am Diet Assoc . 1995;95(7):791-797. PMID: 7797810 ...

  10. Exercise and Pulmonary Hypertension (PH)

    Science.gov (United States)

    ... Situations Find a Doctor PH Care Centers PHA Classroom PHA Registry Insurance Guide Specialty Pharmacy Other Resources ... no published data in the medical literature regarding routine exercise in patients with PAH. However, there are ...

  11. Intracellular pH in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Novak, I; Hug, M; Greger, R

    1997-01-01

    In order to study the mechanism of H+ and HCO3- transport in a HCO3- secreting epithelium, pancreatic ducts, we have measured the intracellular pH (pHi) in this tissue using the pH sensitive probe BCECF. We found that exposures of ducts to solutions containing acetate/acetic acid or NH4+/NH3...... buffers (20 mmol/l) led to pHi changes in accordance with entry of lipid-soluble forms of the buffers, followed by back-regulation of pHi by duct cells. In another type of experiment, changes in extracellular pH of solutions containing HEPES or HCO3-/CO2 buffers led to significant changes in pHi that did....... Under some conditions, these exchangers can be invoked to regulate cell pH....

  12. Modulating Hole Transport in Multilayered Photocathodes with Derivatized p-Type Nickel Oxide and Molecular Assemblies for Solar-Driven Water Splitting

    Energy Technology Data Exchange (ETDEWEB)

    Shan, Bing [Department; Sherman, Benjamin D. [Department; Klug, Christina M. [Center; Nayak, Animesh [Department; Marquard, Seth L. [Department; Liu, Qing [Department; Bullock, R. Morris [Center; Meyer, Thomas J. [Department

    2017-08-31

    We report here a new photocathode composed of a bi-layered doped NiO film topped by a macro-mesoporous ITO (ioITO) layer with molecular assemblies attached to the ioITO surface. The NiO film containing a 2% K+ doped NiO inner layer and a 2% Cu2+ doped NiO outer layer provides sufficient driving force for hole transport after injection to NiO by the molecular assembly. The tri-layered oxide, NiK0.02O | NiCu0.02O | ioITO, sensitized by a ruthenium polypyridyl dye and functionalized with a nickel-based hydrogen evolution catalyst, outperforms its counterpart, NiO | NiO | ioITO, in photocatalytic hydrogen evolution from water over a period of several hours with a Faradaic yield of ~90%.

  13. Programmable pH buffers

    Science.gov (United States)

    Gough, Dara Van; Huber, Dale L.; Bunker, Bruce C.; Roberts, Mark E.

    2017-01-24

    A programmable pH buffer comprises a copolymer that changes pK.sub.a at a lower critical solution temperature (LCST) in water. The copolymer comprises a thermally programmable polymer that undergoes a hydrophobic-to-hydrophilic phase change at the LCST and an electrolytic polymer that exhibits acid-base properties that are responsive to the phase change. The programmable pH buffer can be used to sequester CO.sub.2 into water.

  14. Transportation Life Cycle Assessment (LCA) Synthesis, Phase II

    Science.gov (United States)

    2018-04-24

    The Transportation Life Cycle Assessment (LCA) Synthesis includes an LCA Learning Module Series, case studies, and analytics on the use of the modules. The module series is a set of narrated slideshows on topics related to environmental LCA. Phase I ...

  15. Dysregulated pH in Tumor Microenvironment Checkmates Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jaleh Barar

    2013-12-01

    Full Text Available Introduction: The dysregulation of pH by cancerous cells of solid tumors is able to create a unique milieu that is in favor of progression, invasion and metastasis as well as chemo-/immuno-resistance traits of solid tumors. Bioelements involved in pH dysregulation provide new set of oncotargets, inhibition of which may result in better clinical outcome. Methods: To study the impacts of pH dysregulation, we investigated the tumor development and progression in relation with Warburg effect, glycolysis and formation of aberrant tumor microenvironment. Results: The upregulation of glucose transporter GLUT-1 and several enzymes involve in glycolysis exacerbates this phenomenon. The accumulation of lactic acids in cancer cells provokes upregulation of several transport machineries (MCT-1, NHE-1, CA IX and H+ pump V-ATPase resulting in reinforced efflux of proton into extracellular fluid. This deviant event makes pH to be settled at 7.4 and 6.6 respectively in cancer cells cytoplasm and extracellular fluid within the tumor microenvironment, which in return triggers secretion of lysosomal components (various enzymes in acidic milieu with pH 5 into cytoplasm. All these anomalous phenomena make tumor microenvironment (TME to be exposed to cocktail of various enzymes with acidic pH, upon which extracellular matrix (ECM can be remodeled and even deformed, resulting in emergence of a complex viscose TME with high interstitial fluid pressure. Conclusion: It seems that pH dysregulation is able to remodel various physiologic functions and make solid tumors to become much more invasive and metastatic. It also can cause undesired resistance to chemotherapy and immunotherapy. Hence, cancer therapy needs to be reinforced using specific inhibitors of bioelements involved in pH dysregulation of TME in solid tumors.

  16. Differential effects of buffer pH on Ca2+-induced ROS emission with inhibited mitochondrial complex I and III

    Directory of Open Access Journals (Sweden)

    Daniel P Lindsay

    2015-03-01

    Full Text Available Excessive mitochondrial reactive oxygen species (ROS emission is a critical component in the etiolo-gy of ischemic injury. Complex I and complex III of the electron transport chain are considered the primary sources of ROS emission during cardiac ischemia and reperfusion (IR injury. Several factors modulate ischemic ROS emission, such as an increase in extra-matrix Ca2+, a decrease in extra-matrix pH, and a change in substrate utilization. Here we examined the combined effects of these factors on ROS emission from respiratory complex I and III under conditions of simulated IR injury. Guinea pig heart mitochondria were suspended in experimental buffer at a given pH and incubated with or without CaCl2. Mitochondria were then treated with either pyruvate, a complex I substrate, followed by rote-none, a complex I inhibitor, or succinate, a complex II substrate, followed by antimycin A, a complex III inhibitor. H2O2 release rate and matrix volume were compared with and without adding CaCl2 and at pH 7.15, 6.9, or 6.5 with pyruvate + rotenone or succinate + antimycin A to simulate conditions that may occur during in vivo cardiac IR injury. We found a large increase in H2O2 release with high [CaCl2] and pyruvate + rotenone at pH 6.9, but not at pHs 7.15 or 6.5. Large increases in H2O2 release rate also occurred at each pH with high [CaCl2] and succinate + antimycin A, with the highest levels observed at pH 7.15. The increases in H2O2 release were associated with significant mitochondrial swelling, and both H2O2 release and swelling were abolished by cyclosporine A, a desensitizer of the mitochondrial permeability transition pore. These results indicate that ROS production by complex I and by III is differently affected by buffer pH and Ca2+ loading with mPTP opening. The study sug-gests that changes in the levels of cytosolic Ca2+ and pH during IR alter the relative amounts of ROS produced at mitochondrial respiratory complex I and complex III.

  17. Protective effects of Cassia tora leaves in experimental cataract by modulating intracellular communication, membrane co-transporters, energy metabolism and the ubiquitin-proteasome pathway.

    Science.gov (United States)

    Sreelakshmi, V; Abraham, Annie

    2017-12-01

    Cataract is the clouding of eye lens which causes impairment in vision and accounts for the leading factor of global blindness. Functional food-based prevention of cataract finds application in vision research because of its availability and easy access to all classes of the society. Cassia tora Linn. (Caesalpinaceae) is an edible plant mentioned in the traditional systems of medicine for whole body health, especially to the eyes. The present study evaluates the potential of ethyl acetate fraction of Cassia tora leaves (ECT) on experimental cataract. Cataract was induced by a single subcutaneous injection of sodium selenite (4 μg/g body weight) on 10th day. ECT was supplemented orally from 8th day up to 12th day at a concentration of 5 μg/g body weight and marker parameters were evaluated after 30 days. The production of MPO and the activation of calpain were reduced 52.17% and 36.67% by ECT in lens tissue, respectively. It modulated the energy status by significantly increasing the activity of CCO 1 (55.56%) and ATP production (41.88%). ECT maintained the ionic balance in the lens by reducing the level of sodium (50%) and increasing the level of potassium (42.5%). It also reduced cell junction modifications and preserved a functional ubiquitin-proteasome pathway. The results reinforce the growing attention on wild plant food resources for preventive protection against cataract. The data suggest the value of Cassia tora leaves as a functional food for ameliorating cataract pathology.

  18. Identification of a molecular pH sensor in coral.

    Science.gov (United States)

    Barott, Katie L; Barron, Megan E; Tresguerres, Martin

    2017-11-15

    Maintaining stable intracellular pH (pHi) is essential for homeostasis, and requires the ability to both sense pH changes that may result from internal and external sources, and to regulate downstream compensatory pH pathways. Here we identified the cAMP-producing enzyme soluble adenylyl cyclase (sAC) as the first molecular pH sensor in corals. sAC protein was detected throughout coral tissues, including those involved in symbiosis and calcification. Application of a sAC-specific inhibitor caused significant and reversible pHi acidosis in isolated coral cells under both dark and light conditions, indicating sAC is essential for sensing and regulating pHi perturbations caused by respiration and photosynthesis. Furthermore, pHi regulation during external acidification was also dependent on sAC activity. Thus, sAC is a sensor and regulator of pH disturbances from both metabolic and external origin in corals. Since sAC is present in all coral cell types, and the cAMP pathway can regulate virtually every aspect of cell physiology through post-translational modifications of proteins, sAC is likely to trigger multiple homeostatic mechanisms in response to pH disturbances. This is also the first evidence that sAC modulates pHi in any non-mammalian animal. Since corals are basal metazoans, our results indicate this function is evolutionarily conserved across animals. © 2017 The Author(s).

  19. Economical wireless optical ratiometric pH sensor

    International Nuclear Information System (INIS)

    Vuppu, Sandeep; Kostov, Yordan; Rao, Govind

    2009-01-01

    The development and application of a portable, wireless fluorescence-based optical pH sensor is presented. The design incorporates the MSP430 microcontroller as the control unit, an RF transceiver for wireless communication, digital filters and amplifiers and a USB-based communication module for data transmission. The pH sensor is based on ratiometric fluorescence detection from pH sensitive dye incorporated in a peel-and-stick patch. The ability of the instrument to detect the pH of the solution with contact only between the sensor patch and the solution makes it partially non-invasive. The instrument also has the ability to transmit data wirelessly, enabling its use in processes that entail stringent temperature control and sterility. The use of the microcontroller makes it a reliable, low-cost and low-power device. The luminous intensity of the light source can be digitally controlled to maximize the sensitivity of the instrument. It has a resolution of 0.05 pH. The sensor is accurate and reversible over the pH range of 6.5–9

  20. Data collection and analysis strategies for phMRI.

    Science.gov (United States)

    Mandeville, Joseph B; Liu, Christina H; Vanduffel, Wim; Marota, John J A; Jenkins, Bruce G

    2014-09-01

    Although functional MRI traditionally has been applied mainly to study changes in task-induced brain function, evolving acquisition methodologies and improved knowledge of signal mechanisms have increased the utility of this method for studying responses to pharmacological stimuli, a technique often dubbed "phMRI". The proliferation of higher magnetic field strengths and the use of exogenous contrast agent have boosted detection power, a critical factor for successful phMRI due to the restricted ability to average multiple stimuli within subjects. Receptor-based models of neurovascular coupling, including explicit pharmacological models incorporating receptor densities and affinities and data-driven models that incorporate weak biophysical constraints, have demonstrated compelling descriptions of phMRI signal induced by dopaminergic stimuli. This report describes phMRI acquisition and analysis methodologies, with an emphasis on data-driven analyses. As an example application, statistically efficient data-driven regressors were used to describe the biphasic response to the mu-opioid agonist remifentanil, and antagonism using dopaminergic and GABAergic ligands revealed modulation of the mesolimbic pathway. Results illustrate the power of phMRI as well as our incomplete understanding of mechanisms underlying the signal. Future directions are discussed for phMRI acquisitions in human studies, for evolving analysis methodologies, and for interpretative studies using the new generation of simultaneous PET/MRI scanners. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Sorafenib targets the mitochondrial electron transport chain complexes and ATP synthase to activate the PINK1-Parkin pathway and modulate cellular drug response.

    Science.gov (United States)

    Zhang, Conggang; Liu, Zeyu; Bunker, Eric; Ramirez, Adrian; Lee, Schuyler; Peng, Yinghua; Tan, Aik-Choon; Eckhardt, S Gail; Chapnick, Douglas A; Liu, Xuedong

    2017-09-08

    Sorafenib (Nexavar) is a broad-spectrum multikinase inhibitor that proves effective in treating advanced renal-cell carcinoma and liver cancer. Despite its well-characterized mechanism of action on several established cancer-related protein kinases, sorafenib causes variable responses among human tumors, although the cause for this variation is unknown. In an unbiased screening of an oncology drug library, we found that sorafenib activates recruitment of the ubiquitin E3 ligase Parkin to damaged mitochondria. We show that sorafenib inhibits the activity of both complex II/III of the electron transport chain and ATP synthase. Dual inhibition of these complexes, but not inhibition of each individual complex, stabilizes the serine-threonine protein kinase PINK1 on the mitochondrial outer membrane and activates Parkin. Unlike the protonophore carbonyl cyanide m -chlorophenylhydrazone, which activates the mitophagy response, sorafenib treatment triggers PINK1/Parkin-dependent cellular apoptosis, which is attenuated upon Bcl-2 overexpression. In summary, our results reveal a new mechanism of action for sorafenib as a mitocan and suggest that high Parkin activity levels could make tumor cells more sensitive to sorafenib's actions, providing one possible explanation why Parkin may be a tumor suppressor gene. These insights could be useful in developing new rationally designed combination therapies with sorafenib. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Electric field and substrate–induced modulation of spin-polarized transport in graphene nanoribbons on A3B5 semiconductors

    International Nuclear Information System (INIS)

    Ilyasov, Victor V.; Nguyen, Chuong V.; Ershov, Igor V.; Hieu, Nguyen N.

    2015-01-01

    In this work, we present the density functional theory calculations of the effect of an oriented electric field on the electronic structure and spin-polarized transport in a one dimensional (1D) zigzag graphene nanoribbon (ZGNR) channel placed on a wide bandgap semiconductor of the A3B5 type. Our calculations show that carrier mobility in the 1D semiconductor channel of the ZGNR/A3B5(0001) type is in the range from 1.7×10 4 to 30.5×10 4 cm 2 /Vs and can be controlled by an electric field. In particular, at the critical value of the positive potential, even though hole mobility in an one-dimensional 8-ZGNR/h-BN semiconductor channel for spin down electron subsystems is equal to zero, hole mobility can be increased to 4.1×10 5 cm 2 /Vs for spin up electron subsystems. We found that band gap and carrier mobility in a 1D semiconductor channel of the ZGNR/A3B5(0001) type depend strongly on an external electric field. With these extraordinary properties, ZGNR/A3B5(0001) can become a promising materials for application in nanospintronic devices

  3. Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice.

    Science.gov (United States)

    Slijepcevic, Davor; Roscam Abbing, Reinout L P; Katafuchi, Takeshi; Blank, Antje; Donkers, Joanne M; van Hoppe, Stéphanie; de Waart, Dirk R; Tolenaars, Dagmar; van der Meer, Jonathan H M; Wildenberg, Manon; Beuers, Ulrich; Oude Elferink, Ronald P J; Schinkel, Alfred H; van de Graaf, Stan F J

    2017-11-01

    The Na + -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. Mice or healthy volunteers were treated with myrcludex B. Hepatic bile acid uptake kinetics were determined in wild-type (WT), organic anion transporting polypeptide (OATP) knockout mice (lacking Slco1a/1b isoforms), and human OATP1B1-transgenic mice. Effects of fibroblast growth factor 19 (FGF19) on hepatic transporter mRNA levels were assessed in rat hepatoma cells and in mice by peptide injection or adeno-associated virus-mediated overexpression. NTCP inhibition using myrcludex B had only moderate effects on bile acid kinetics in WT mice, but completely inhibited active transport of conjugated bile acid species in OATP knockout mice. Cholesterol 7α-hydroxylase Cyp7a1 expression was strongly down-regulated upon prolonged inhibition of hepatic uptake of conjugated bile acids. Fgf15 (mouse counterpart of FGF19) expression was induced in hypercholanemic OATP and NTCP knockout mice, as well as in myrcludex B-treated cholestatic mice, whereas plasma FGF19 was not induced in humans treated with myrcludex B. Fgf15/FGF19 expression was induced in polarized human enterocyte-models and mouse organoids by basolateral incubation with a high concentration (1 mM) of conjugated bile acids. NTCP and OATPs contribute to hepatic uptake of conjugated bile acids in mice, whereas the predominant uptake in humans is NTCP mediated. Enterocytes sense highly elevated levels of (conjugated) bile acids in the systemic circulation to induce FGF15/19, which modulates hepatic bile acid synthesis and uptake. (Hepatology 2017;66:1631-1643).

  4. Bystruktur og transport

    DEFF Research Database (Denmark)

    Nielsen, Thomas Alexander Sick

    2003-01-01

    Paperet præsenterer hovedkonklusionerne fra et PhD-studie af sammenhængene mellem bystruktur (særligt boliglokalisering) og transport i Aalborg. Det konkluderes at boliglokaliseringen har væsentlig betydning for transporten i det daglige. Det gælder især lokaliseringen i forhold til det samlede...

  5. GREET Pretreatment Module

    Energy Technology Data Exchange (ETDEWEB)

    Adom, Felix K. [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division; Dunn, Jennifer B. [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division; Han, Jeongwoo [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division

    2014-09-01

    A wide range of biofuels and biochemicals can be produced from cellulosic biomass via different pretreatment technologies that yield sugars. Process simulations of dilute acid and ammonia fiber expansion pretreatment processes and subsequent hydrolysis were developed in Aspen Plus for four lignocellulosic feedstocks (corn stover, miscanthus, switchgrass, and poplar). This processing yields sugars that can be subsequently converted to biofuels or biochemical. Material and energy consumption data from Aspen Plus were then compiled in a new Greenhouses Gases, Regulated Emissions, and Energy Use in Transportation (GREETTM) pretreatment module. The module estimates the cradle-to-gate fossil energy consumption (FEC) and greenhouse gas (GHG) emissions associated with producing fermentable sugars. This report documents the data and methodology used to develop this module and the cradle-to-gate FEC and GHG emissions that result from producing fermentable sugars.

  6. Nicotine transport in lung and non-lung epithelial cells.

    Science.gov (United States)

    Takano, Mikihisa; Kamei, Hidetaka; Nagahiro, Machi; Kawami, Masashi; Yumoto, Ryoko

    2017-11-01

    Nicotine is rapidly absorbed from the lung alveoli into systemic circulation during cigarette smoking. However, mechanism underlying nicotine transport in alveolar epithelial cells is not well understood to date. In the present study, we characterized nicotine uptake in lung epithelial cell lines A549 and NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Characteristics of [ 3 H]nicotine uptake was studied using these cell lines. Nicotine uptake in A549 cells occurred in a time- and temperature-dependent manner and showed saturation kinetics, with a Km value of 0.31mM. Treatment with some organic cations such as diphenhydramine and pyrilamine inhibited nicotine uptake, whereas treatment with organic cations such as carnitine and tetraethylammonium did not affect nicotine uptake. Extracellular pH markedly affected nicotine uptake, with high nicotine uptake being observed at high pH up to 11.0. Modulation of intracellular pH with ammonium chloride also affected nicotine uptake. Treatment with valinomycin, a potassium ionophore, did not significantly affect nicotine uptake, indicating that nicotine uptake is an electroneutral process. For comparison, we assessed the characteristics of nicotine uptake in another lung epithelial cell line NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Interestingly, these cell lines showed similar characteristics of nicotine uptake with respect to pH dependency and inhibition by various organic cations. The present findings suggest that a similar or the same pH-dependent transport system is involved in nicotine uptake in these cell lines. A novel molecular mechanism of nicotine transport is proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Modulation of cAMP levels by high-fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression.

    Science.gov (United States)

    Zingg, Jean-Marc; Hasan, Syeda T; Nakagawa, Kiyotaka; Canepa, Elisa; Ricciarelli, Roberta; Villacorta, Luis; Azzi, Angelo; Meydani, Mohsen

    2017-01-02

    Curcumin, a polyphenol from turmeric (Curcuma longa), reduces inflammation, atherosclerosis, and obesity in several animal studies. In Ldlr -/- mice fed a high-fat diet (HFD), curcumin reduces plasma lipid levels, therefore contributing to a lower accumulation of lipids and to reduced expression of fatty acid transport proteins (CD36/FAT, FABP4/aP2) in peritoneal macrophages. In this study, we analyzed the molecular mechanisms by which curcumin (500, 1000, 1500 mg/kg diet, for 4 months) may influence plasma and tissue lipid levels in Ldlr -/- mice fed an HFD. In liver, HFD significantly suppressed cAMP levels, and curcumin restored almost normal levels. Similar trends were observed in adipose tissues, but not in brain, skeletal muscle, spleen, and kidney. Treatment with curcumin increased phosphorylation of CREB in liver, what may play a role in regulatory effects of curcumin in lipid homeostasis. In cell lines, curcumin increased the level of cAMP, activated the transcription factor CREB and the human CD36 promoter via a sequence containing a consensus CREB response element. Regulatory effects of HFD and Cur on gene expression were observed in liver, less in skeletal muscle and not in brain. Since the cAMP/protein kinase A (PKA)/CREB pathway plays an important role in lipid homeostasis, energy expenditure, and thermogenesis by increasing lipolysis and fatty acid β-oxidation, an increase in cAMP levels induced by curcumin may contribute to its hypolipidemic and anti-atherosclerotic effects. © 2016 BioFactors, 43(1):42-53, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  8. Inhibition of K+ transport through Na+, K+-ATPase by capsazepine: role of membrane span 10 of the α-subunit in the modulation of ion gating.

    Science.gov (United States)

    Mahmmoud, Yasser A; Shattock, Michael; Cornelius, Flemming; Pavlovic, Davor

    2014-01-01

    Capsazepine (CPZ) inhibits Na+,K+-ATPase-mediated K+-dependent ATP hydrolysis with no effect on Na+-ATPase activity. In this study we have investigated the functional effects of CPZ on Na+,K+-ATPase in intact cells. We have also used well established biochemical and biophysical techniques to understand how CPZ modifies the catalytic subunit of Na+,K+-ATPase. In isolated rat cardiomyocytes, CPZ abolished Na+,K+-ATPase current in the presence of extracellular K+. In contrast, CPZ stimulated pump current in the absence of extracellular K+. Similar conclusions were attained using HEK293 cells loaded with the Na+ sensitive dye Asante NaTRIUM green. Proteolytic cleavage of pig kidney Na+,K+-ATPase indicated that CPZ stabilizes ion interaction with the K+ sites. The distal part of membrane span 10 (M10) of the α-subunit was exposed to trypsin cleavage in the presence of guanidinum ions, which function as Na+ congener at the Na+ specific site. This effect of guanidinium was amplified by treatment with CPZ. Fluorescence of the membrane potential sensitive dye, oxonol VI, was measured following addition of substrates to reconstituted inside-out Na+,K+-ATPase. CPZ increased oxonol VI fluorescence in the absence of K+, reflecting increased Na+ efflux through the pump. Surprisingly, CPZ induced an ATP-independent increase in fluorescence in the presence of high extravesicular K+, likely indicating opening of an intracellular pathway selective for K+. As revealed by the recent crystal structure of the E1.AlF4-.ADP.3Na+ form of the pig kidney Na+,K+-ATPase, movements of M5 of the α-subunit, which regulate ion selectivity, are controlled by the C-terminal tail that extends from M10. We propose that movements of M10 and its cytoplasmic extension is affected by CPZ, thereby regulating ion selectivity and transport through the K+ sites in Na+,K+-ATPase.

  9. Inhibition of K+ transport through Na+, K+-ATPase by capsazepine: role of membrane span 10 of the α-subunit in the modulation of ion gating.

    Directory of Open Access Journals (Sweden)

    Yasser A Mahmmoud

    Full Text Available Capsazepine (CPZ inhibits Na+,K+-ATPase-mediated K+-dependent ATP hydrolysis with no effect on Na+-ATPase activity. In this study we have investigated the functional effects of CPZ on Na+,K+-ATPase in intact cells. We have also used well established biochemical and biophysical techniques to understand how CPZ modifies the catalytic subunit of Na+,K+-ATPase. In isolated rat cardiomyocytes, CPZ abolished Na+,K+-ATPase current in the presence of extracellular K+. In contrast, CPZ stimulated pump current in the absence of extracellular K+. Similar conclusions were attained using HEK293 cells loaded with the Na+ sensitive dye Asante NaTRIUM green. Proteolytic cleavage of pig kidney Na+,K+-ATPase indicated that CPZ stabilizes ion interaction with the K+ sites. The distal part of membrane span 10 (M10 of the α-subunit was exposed to trypsin cleavage in the presence of guanidinum ions, which function as Na+ congener at the Na+ specific site. This effect of guanidinium was amplified by treatment with CPZ. Fluorescence of the membrane potential sensitive dye, oxonol VI, was measured following addition of substrates to reconstituted inside-out Na+,K+-ATPase. CPZ increased oxonol VI fluorescence in the absence of K+, reflecting increased Na+ efflux through the pump. Surprisingly, CPZ induced an ATP-independent increase in fluorescence in the presence of high extravesicular K+, likely indicating opening of an intracellular pathway selective for K+. As revealed by the recent crystal structure of the E1.AlF4-.ADP.3Na+ form of the pig kidney Na+,K+-ATPase, movements of M5 of the α-subunit, which regulate ion selectivity, are controlled by the C-terminal tail that extends from M10. We propose that movements of M10 and its cytoplasmic extension is affected by CPZ, thereby regulating ion selectivity and transport through the K+ sites in Na+,K+-ATPase.

  10. Integrated operation of the photorespiratory cycle and cytosolic metabolism in the modulation of primary nitrogen assimilation and export of organic N-transport compounds from leaves: a hypothesis.

    Science.gov (United States)

    Misra, Jitendra B

    2014-02-15

    Photorespiration is generally considered to be an essentially dissipative process, although it performs some protective and essential functions. A theoretical appraisal indicates that the loss of freshly assimilated CO2 due to photorespiration in well-watered plants may not be as high as generally believed. Even under moderately adverse conditions, these losses may not exceed 10%. The photorespiratory metabolism of the source leaves of well-watered and well-nourished crop plants ought to be different from that of other leaves because the fluxes of the export of both carbohydrates and organic N-transport compounds in source leaves is quite high. With a heuristic approach that involved the dovetailing of certain metabolic steps with the photorespiratory cycle (PR-cycle), a novel network is proposed to operate in the source-leaves of well-watered and well-nourished plants. This network allows for the diversion of metabolites from their cyclic-routes in sizeable quantities. With the removal of considerable quantities of glycine and serine from the cyclic route, the number of RuBP oxygenation events would be several times those of the formation of hydroxypyruvate. Thus, to an extreme extent, photorespiratory metabolism would become open-ended and involve much less futile recycling of glycine and serine. Conversion of glyoxylate to glycine has been proposed to be a crucial step in the determination of the relative rates of the futile (cyclic) and anabolic (open-ended) routes. Thus, in the source leaves of well-watered and well-nourished plants, the importance of the cyclic route is limited to the salvaging of photorespiratory intermediates for the regeneration of RuBP. The proposed network is resilient enough to coordinate the rates of the assimilation of carbon and nitrogen in accordance with the moisture and N-fertility statuses of the soil. Copyright © 2013 Elsevier GmbH. All rights reserved.

  11. Intracellular pH in sperm physiology.

    Science.gov (United States)

    Nishigaki, Takuya; José, Omar; González-Cota, Ana Laura; Romero, Francisco; Treviño, Claudia L; Darszon, Alberto

    2014-08-01

    Intracellular pH (pHi) regulation is essential for cell function. Notably, several unique sperm ion transporters and enzymes whose elimination causes infertility are either pHi dependent or somehow related to pHi regulation. Amongst them are: CatSper, a Ca(2+) channel; Slo3, a K(+) channel; the sperm-specific Na(+)/H(+) exchanger and the soluble adenylyl cyclase. It is thus clear that pHi regulation is of the utmost importance for sperm physiology. This review briefly summarizes the key components involved in pHi regulation, their characteristics and participation in fundamental sperm functions such as motility, maturation and the acrosome reaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Brain-derived neurotrophic factor (Val66Met and serotonin transporter (5-HTTLPR polymorphisms modulate plasticity in inhibitory control performance over time but independent of inhibitory control training

    Directory of Open Access Journals (Sweden)

    Sören Enge

    2016-07-01

    Full Text Available Several studies reported training-induced improvements in executive function tasks and also observed transfer to untrained tasks. However, the results are mixed and there is large interindividual variability within and across studies. Given that training-related performance changes would require modification, growth or differentiation at the cellular and synaptic level in the brain, research on critical moderators of brain plasticity potentially explaining such changes is needed. In the present study, a pre-post-follow-up design (N=122 and a three-weeks training of two response inhibition tasks (Go/NoGo and Stop-Signal was employed and genetic variation (Val66Met in the brain-derived neurotrophic factor (BDNF promoting differentiation and activity-dependent synaptic plasticity was examined. Because Serotonin (5-HT signaling and the interplay of BDNF and 5-HT are known to critically mediate brain plasticity, genetic variation in the 5-HT transporter (5-HTTLPR was also addressed. The overall results show that the kind of training (i.e., adaptive vs. non-adaptive did not evoke genotype-dependent differences. However, in the Go/NoGo task, better inhibition performance (lower commission errors were observed for BDNF Val/Val genotype carriers compared to Met-allele ones supporting similar findings from other cognitive tasks. Additionally, a gene-gene interaction suggests a more impulsive response pattern (faster responses accompanied by higher commission error rates in homozygous l-allele carriers relative to those with the s-allele of 5-HTTLPR. This, however, is true only in the presence of the Met-allele of BDNF, while the Val/Val genotype seems to compensate for such non-adaptive responding. Intriguingly, similar results were obtained for the Stop-Signal task. Here, differences emerged at post-testing, while no differences were observed at T1. In sum, although no genotype-dependent differences between the relevant training groups emerged suggesting

  13. pH Sensing and Regulation in Cancer

    Directory of Open Access Journals (Sweden)

    Mehdi eDamaghi

    2013-12-01

    Full Text Available Cells maintain intracellular pH (pHi within a narrow range (7.1-7.2 by controlling membrane proton pumps and transporters whose activity is set by intra-cytoplasmic pH sensors. These sensors have the ability to recognize and induce cellular responses to maintain the intracellular pH, often at the expense of acidifying the extracellular pH. In turn, extracellular acidification impacts cells via specific acid-sensing ion channels (ASICs and proton-sensing G-protein coupled receptors (GPCRs. In this review, we will discuss some of the major players in proton sensing at the plasma membrane and their downstream consequences in cancer cells and how these pH-mediated changes affect processes such as migration and metastasis. The complex mechanisms by which they transduce acid pH signals to the cytoplasm and nucleus are not well understood. However, there is evidence that expression of proton-sensing GPCRs such as GPR4, TDAG8, and OGR1 can regulate aspects of tumorigenesis and invasion, including colfilin and talin regulated actin (de-polymerization. Major mechanisms for maintenance of pHi homeostasis include monocarboxylate, bicarbonate and proton transporters. Notably, there is little evidence suggesting a link between their activities and those of the extracellular H+-sensors, suggesting a mechanistic disconnect between intra- and extra-cellular pH. Understanding the mechanisms of pH sensing and regulation may lead to novel and informed therapeutic strategies that can target acidosis, a common physical hallmark of solid tumors.

  14. Regulation of pH in human skeletal muscle: adaptations to physical activity

    DEFF Research Database (Denmark)

    Juel, C

    2008-01-01

    -transport) and describes the contribution of each transport system in pH regulation at rest and during muscle activity. It is reported that the mechanisms involved in pH regulation can undergo adaptational changes in association with physical activity and that these changes are of functional importance....... resonance technique to exercise experiments including blood sampling and muscle biopsies. The present review characterizes the cellular buffering system as well as the most important membrane transport systems involved (Na(+)/H(+) exchange, Na-bicarbonate co-transport and lactate/H(+) co...

  15. Modulation of microRNA Expression in Subjects with Metabolic Syndrome and Decrease of Cholesterol Efflux from Macrophages via microRNA-33-Mediated Attenuation of ATP-Binding Cassette Transporter A1 Expression by Statins.

    Directory of Open Access Journals (Sweden)

    Wei-Ming Chen

    Full Text Available Metabolic syndrome (MetS is a complicated health problem that encompasses a variety of metabolic disorders. In this study, we analyzed the relationship between the major biochemical parameters associated with MetS and circulating levels of microRNA (miR-33, miR-103, and miR-155. We found that miRNA-33 levels were positively correlated with levels of fasting blood glucose, glycosylated hemoglobin A1c, total cholesterol, LDL-cholesterol, and triacylglycerol, but negatively correlated with HDL-cholesterol levels. In the cellular study, miR-33 levels were increased in macrophages treated with high glucose and cholesterol-lowering drugs atorvastatin and pitavastatin. miR-33 has been reported to play an essential role in cholesterol homeostasis through ATP-binding cassette transporter A1 (ABCA1 regulation and reverse cholesterol transport. However, the molecular mechanism underlying the linkage between miR-33 and statin treatment remains unclear. In the present study, we investigated whether atorvastatin and pitavastatin exert their functions through the modulation of miR-33 and ABCA1-mediated cholesterol efflux from macrophages. The results showed that treatment of the statins up-regulated miR-33 expression, but down-regulated ABCA1 mRNA levels in RAW264.7 cells and bone marrow-derived macrophages. Statin-mediated ABCA1 regulation occurs at the post-transcriptional level through targeting of the 3'-UTR of the ABCA1 transcript by miR-33. Additionally, we found significant down-regulation of ABCA1 protein expression in macrophages treated with statins. Finally, we showed that high glucose and statin treatment significantly suppressed cholesterol efflux from macrophages. These findings have highlighted the complexity of statins, which may exert detrimental effects on metabolic abnormalities through regulation of miR-33 target genes.

  16. Modulation of microRNA Expression in Subjects with Metabolic Syndrome and Decrease of Cholesterol Efflux from Macrophages via microRNA-33-Mediated Attenuation of ATP-Binding Cassette Transporter A1 Expression by Statins.

    Science.gov (United States)

    Chen, Wei-Ming; Sheu, Wayne H-H; Tseng, Pei-Chi; Lee, Tzong-Shyuan; Lee, Wen-Jane; Chang, Pey-Jium; Chiang, An-Na

    2016-01-01

    Metabolic syndrome (MetS) is a complicated health problem that encompasses a variety of metabolic disorders. In this study, we analyzed the relationship between the major biochemical parameters associated with MetS and circulating levels of microRNA (miR)-33, miR-103, and miR-155. We found that miRNA-33 levels were positively correlated with levels of fasting blood glucose, glycosylated hemoglobin A1c, total cholesterol, LDL-cholesterol, and triacylglycerol, but negatively correlated with HDL-cholesterol levels. In the cellular study, miR-33 levels were increased in macrophages treated with high glucose and cholesterol-lowering drugs atorvastatin and pitavastatin. miR-33 has been reported to play an essential role in cholesterol homeostasis through ATP-binding cassette transporter A1 (ABCA1) regulation and reverse cholesterol transport. However, the molecular mechanism underlying the linkage between miR-33 and statin treatment remains unclear. In the present study, we investigated whether atorvastatin and pitavastatin exert their functions through the modulation of miR-33 and ABCA1-mediated cholesterol efflux from macrophages. The results showed that treatment of the statins up-regulated miR-33 expression, but down-regulated ABCA1 mRNA levels in RAW264.7 cells and bone marrow-derived macrophages. Statin-mediated ABCA1 regulation occurs at the post-transcriptional level through targeting of the 3'-UTR of the ABCA1 transcript by miR-33. Additionally, we found significant down-regulation of ABCA1 protein expression in macrophages treated with statins. Finally, we showed that high glucose and statin treatment significantly suppressed cholesterol efflux from macrophages. These findings have highlighted the complexity of statins, which may exert detrimental effects on metabolic abnormalities through regulation of miR-33 target genes.

  17. The chemistry, physiology and pathology of pH in cancer.

    Science.gov (United States)

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

    2014-03-19

    Cell survival is conditional on the maintenance of a favourable acid-base balance (pH). Owing to intensive respiratory CO2 and lactic acid production, cancer cells are exposed continuously to large acid-base fluxes, which would disturb pH if uncorrected. The large cellular reservoir of H(+)-binding sites can buffer pH changes but, on its own, is inadequate to regulate intracellular pH. To stabilize intracellular pH at a favourable level, cells control trans-membrane traffic of H(+)-ions (or their chemical equivalents, e.g. ) using specialized transporter proteins sensitive to pH. In poorly perfused tumours, additional diffusion-reaction mechanisms, involving carbonic anhydrase (CA) enzymes, fine-tune control extracellular pH. The ability of H(+)-ions to change the ionization state of proteins underlies the exquisite pH sensitivity of cellular behaviour, including key processes in cancer formation and metastasis (proliferation, cell cycle, transformation, migration). Elevated metabolism, weakened cell-to-capillary diffusive coupling, and adaptations involving H(+)/H(+)-equivalent transporters and extracellular-facing CAs give cancer cells the means to manipulate micro-environmental acidity, a cancer hallmark. Through genetic instability, the cellular apparatus for regulating and sensing pH is able to adapt to extracellular acidity, driving disease progression. The therapeutic potential of disturbing this sequence by targeting H(+)/H(+)-equivalent transporters, buffering or CAs is being investigated, using monoclonal antibodies and small-molecule inhibitors.

  18. pH Gradient Reversal: An Emerging Hallmark of Cancers.

    Science.gov (United States)

    Sharma, Mohit; Astekar, Madhusudan; Soi, Sonal; Manjunatha, Bhari S; Shetty, Devi C; Radhakrishnan, Raghu

    2015-01-01

    Several tumors exhibit pH gradient reversal, with acidification of extracellular pH (pHe) and alkalinization of intracellular pH (pHi). The pH gradient reversal is evident even during the preliminary stages of tumorigenesis and is crucial for survival and propagation of tumors, irrespective of their pathology, genetics and origins. Moreover, this hallmark seems to be present ubiquitously in all malignant tumors. Based on these facts, we propose a new emerging hallmark of cancer "pH gradient reversal". Normalizing pH gradient reversal through inhibition of various proton transporters such as Na(+)-H(+) exchanger (NHE), Vacuolar-type H(+)-ATPase (V-ATPase), H(+)/K(+)-ATPases and carbonic anhydrases (CAs) has demonstrated substantial therapeutic benefits. Indeed, inhibition of NHE1 is now being regarded as the latest concept in cancer treatment. A recent patent deals with the utilization of cis-Urocanic acid to acidify the pHi and induce apoptosis in tumors. Another patent reports therapeutic benefit by inhibiting Lactate Dehydrogenase - 5 (LDH-5) in various cancers. Several patents have been formulated by designing drugs activated through acidic pHe providing a cancer specific action. The purpose of this review is to analyze the available literature and help design selective therapies that could be a valuable adjunct to the conventional therapies or even replace them.

  19. Paulette Gray, Ph.D.

    Science.gov (United States)

    Paulette S. Gray, Ph.D. is the Director for the Division of Extramural Activities (DEA). As the director of the division, she is responsible for the overall scientific, fiscal, and administrative management of the division, including broad strategic planning, development, implementation, and evaluation.

  20. pH in Action

    NARCIS (Netherlands)

    Tijskens, L.M.M.; Biekman, E.S.A.

    2001-01-01

    Based on fundamental chemical relations, well-established in chemical engineering and chemical technology over almost a century, the effects of pH in food and agricultural products will be deduced for different situations and processes. Based on simple equilibria and dissociation of water, salts,

  1. Neuronal pH regulation

    DEFF Research Database (Denmark)

    Vorstrup, S; Jensen, K E; Thomsen, C

    1989-01-01

    The intracellular pH in the brain was studied in six healthy volunteers before and immediately after the administration of 2 g of acetazolamide. Phosphorus-31 nuclear magnetic resonance spectroscopy by a 1.5 tesla whole-body scanner was used. The chemical shift between the inorganic phosphate...

  2. Fabrication of triple-labeled polyelectrolyte microcapsules for localized ratiometric pH sensing.

    Science.gov (United States)

    Song, Xiaoxue; Li, Huanbin; Tong, Weijun; Gao, Changyou

    2014-02-15

    Encapsulation of pH sensitive fluorophores as reporting molecules provides a powerful approach to visualize the transportation of multilayer capsules. In this study, two pH sensitive dyes (fluorescein and oregon green) and one pH insensitive dye (rhodamine B) were simultaneously labeled on the microcapsules to fabricate ratiometric pH sensors. The fluorescence of the triple-labeled microcapsule sensors was robust and nearly independent of other intracellular species. With a dynamic pH measurement range of 3.3-6.5, the microcapsules can report their localized pH at a real time. Cell culture experiments showed that the microcapsules could be internalized by RAW 246.7 cells naturally and finally accumulated in acidic organelles with a pH value of 5.08 ± 0.59 (mean ± s.d.; n=162). Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Some auxiliary technology equipment for ATLAS hadron calorimeter module and submodule manipulations and the quality control of the assembled module

    International Nuclear Information System (INIS)

    Budagov, Yu.; Lebedev, A.; Lomakin, Yu.; Romanov, V.; Rusakovich, N.; Shchelchkov, A.; Sisakyan, A.; Sorokina, Yu.; Topilin, N.; Kul'chitskij, Yu.

    1997-01-01

    Describing of the auxiliary technology equipment for the submodule and module manipulations is presented. The results of the 0-module beam incoming control are given. The variations of the assembled module control measurements are described. The description of the construction for the 0-module transportation is presented

  4. Intracellular pH homeostasis in Leishmania donovani amastigotes and promastigotes

    International Nuclear Information System (INIS)

    Glaser, T.A.; Baatz, J.E.; Kreishman, G.P.; Mukkada, A.J.

    1988-01-01

    Intracellular pH and pH gradients of Leishmania donovani amastigotes and promastigotes were determined over a broad range of extracellular pH values. Intracellular pH was determined by 31 P NMR and by equilibrium distribution studies with 5,5-dimethyloxazolidine-2,4-dione or methylamine. Promastigotes maintain intracellular pH values close to neutral between extracellular pH values of 5.0 and 7.4. Amastigote intracellular pH is maintained close to neutral at external pH values as low as 4.0. Both life stages maintain a positive pH gradient to an extracellular pH of 7.4, which is important for active transport of substrates. Treatment with ionophores, such as nigericin and carbonyl cyanide m-chlorophenylhydrazone and the ATPase inhibitor dicyclohexylcarbodiimide, reduced pH gradients in both stages. Maintenance of intracellular pH in the physiologic range is especially relevant for the survival of the amastigote in its acidic in vivo environment

  5. Forage Harvest and Transport Costs

    Energy Technology Data Exchange (ETDEWEB)

    Butler, J.; Downing, M.; Turhollow, A.

    1998-12-01

    An engineering-economic approach is used to calculate harvest, in-field transport, and over-the-road transport costs for hay as bales and modules, silage, and crop residues as bales and modules. Costs included are equipment depreciation interest; fuel, lube, and oil; repairs; insurance, housing, and taxes; and labor. Field preparation, pest control, fertilizer, land, and overhead are excluded from the costs calculated Equipment is constrained by power available, throughput or carrying capacity, and field speed.

  6. Industrial PhD report: Sustainable Innovation

    DEFF Research Database (Denmark)

    Olesen, Gitte Gylling Hammershøj

    2011-01-01

    Erhvervs PhD rapport udarbejdet i tilknytning til Erhvervs PhD kurset der er obligatorisk for Erhvervs PhD studerende. Rapporten omhandler relationer melllem den akademiske verden og industrien i sammenhæng med PhD projektet, betragtet og analyseret gennem teori om bæredygtig innovation....

  7. A ph sensor based on a flexible substrate

    Science.gov (United States)

    Huang, Wen-Ding

    implanted inside the esophagus. Our pH electrode can monitor the pH changes of gastric juice in real time when the reflux happening in the esophagus. Our micro flexible pH sensor performed clear responses in each distinct pH reflux episode quickly and accurately comparing with the other commercial pH monitoring system. For the food freshness monitoring applications, we used the flexible pH sensor as a freshness indicator to monitor the pH changing profile during the food spoilage procedure. The sensor was then embedded with radio frequency identification (RFID) based passive telemetry enabling remote monitoring of food freshness. In the result, our pH-wireless RFID system presented 633Hz/pH of the sensitivity in the frequency calibration. The calibration of stability and dynamical response of the RFID system were also demonstrated before the test on food freshness monitoring. Finally, a white fish meat for long term spoilage procedure monitoring was applied and tested by using our wireless IrOx pH sensing system. Our RFID pH sensing module is able to monitor, collect and transmit the pH information continuously for 18 hours during the food spoilage procedure. In this dissertation, a micro size of IrOx/AgCl pH sensor was fabricated on a flexible substrate. The physical properties of the IrO x thin film was verified in the work. The different sensing capability such as the sensitivity, stability, reversibility, response time, repeatability, selectivity, and temperature dependence was then demonstrated in this work. After the different in-vitro tests, the pH sensor were embedded with our passive RFID circuitry for the in-vivo GERD diagnosis and food freshness monitoring application. Our wireless pH sensing system was able to deliver the accurate and quick pH sensing data wirelessly. In conclusion, our deformable IrOx pH electrodes have been demonstrated with the advantages of accommodating and conforming sensors in small spaces or curved surfaces. This miniature IrOx pH sensor

  8. Involvement of Histidine Residue His382 in pH Regulation of MCT4 Activity.

    Directory of Open Access Journals (Sweden)

    Shotaro Sasaki

    Full Text Available Monocarboxylate transporter 4 (MCT4 is a pH-dependent bi-directional lactate transporter. Transport of lactate via MCT4 is increased by extracellular acidification. We investigated the critical histidine residue involved in pH regulation of MCT4 function. Transport of lactate via MCT4 was measured by using a Xenopus laevis oocyte expression system. MCT4-mediated lactate transport was inhibited by Zn2+ in a pH physiological condition but not in an acidic condition. The histidine modifier DEPC (diethyl pyrocarbonate reduced MCT4 activity but did not completely inactivate MCT4. After treatment with DEPC, pH regulation of MCT4 function was completely knocked out. Inhibitory effects of DEPC were reversed by hydroxylamine and suppressed in the presence of excess lactate and Zn2+. Therefore, we performed an experiment in which the extracellular histidine residue was replaced with alanine. Consequently, the pH regulation of MCT4-H382A function was also knocked out. Our findings demonstrate that the histidine residue His382 in the extracellular loop of the transporter is essential for pH regulation of MCT4-mediated substrate transport activity.

  9. pH sensing and regulation in cancer.

    Science.gov (United States)

    Damaghi, Mehdi; Wojtkowiak, Jonathan W; Gillies, Robert J

    2013-12-17

    Cells maintain intracellular pH (pHi) within a narrow range (7.1-7.2) by controlling membrane proton pumps and transporters whose activity is set by intra-cytoplasmic pH sensors. These sensors have the ability to recognize and induce cellular responses to maintain the pHi, often at the expense of acidifying the extracellular pH. In turn, extracellular acidification impacts cells via specific acid-sensing ion channels (ASICs) and proton-sensing G-protein coupled receptors (GPCRs). In this review, we will discuss some of the major players in proton sensing at the plasma membrane and their downstream consequences in cancer cells and how these pH-mediated changes affect processes such as migration and metastasis. The complex mechanisms by which they transduce acid pH signals to the cytoplasm and nucleus are not well understood. However, there is evidence that expression of proton-sensing GPCRs such as GPR4, TDAG8, and OGR1 can regulate aspects of tumorigenesis and invasion, including cofilin and talin regulated actin (de-)polymerization. Major mechanisms for maintenance of pHi homeostasis include monocarboxylate, bicarbonate, and proton transporters. Notably, there is little evidence suggesting a link between their activities and those of the extracellular H(+)-sensors, suggesting a mechanistic disconnect between intra- and extracellular pH. Understanding the mechanisms of pH sensing and regulation may lead to novel and informed therapeutic strategies that can target acidosis, a common physical hallmark of solid tumors.

  10. Dual regulation of the native ClC-K2 chloride channel in the distal nephron by voltage and pH.

    Science.gov (United States)

    Pinelli, Laurent; Nissant, Antoine; Edwards, Aurélie; Lourdel, Stéphane; Teulon, Jacques; Paulais, Marc

    2016-09-01

    ClC-K2, a member of the ClC family of Cl(-) channels and transporters, forms the major basolateral Cl(-) conductance in distal nephron epithelial cells and therefore plays a central role in renal Cl(-) absorption. However, its regulation remains largely unknown because of the fact that recombinant ClC-K2 has not yet been studied at the single-channel level. In the present study, we investigate the effects of voltage, pH, Cl(-), and Ca(2+) on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The ∼10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pHi) and extracellular pH (pHo) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pHo shifts the curve toward negative voltages. In addition, pHi, pHo, and extracellular Ca(2+) strongly increase activity, mainly because of an increase in the number of active channels with a comparatively minor effect on channel open probability. Furthermore, voltage alters both the number of active channels and their open probability, whereas intracellular Cl(-) has little influence. We propose that changes in the number of active channels correspond to them entering or leaving an inactivated state, whereas modulation of open probability corresponds to common gating by these channels. We suggest that pH, through the combined effects of pHi and pHo on ClC-K2, might be a key regulator of NaCl absorption and Cl(-)/HCO3 (-) exchange in type B intercalated cells. © 2016 Pinelli et al.

  11. Irreducible Specht modules are signed Young modules

    OpenAIRE

    Hemmer, David J.

    2005-01-01

    Recently Donkin defined signed Young modules as a simultaneous generalization of Young and twisted Young modules for the symmetric group. We show that in odd characteristic, if a Specht module $S^\\lambda$ is irreducible, then $S^\\lambda$ is a signed Young module. Thus the set of irreducible Specht modules coincides with the set of irreducible signed Young modules. This provides evidence for our conjecture that the signed Young modules are precisely the class of indecomposable self-dual module...

  12. Graphene Channel Liquid Container Field Effect Transistor as ph Sensor

    International Nuclear Information System (INIS)

    Li, X.; Shi, J.; Pang, J.; Liu, W.; Wang, X.; Liu, H.

    2014-01-01

    Graphene channel liquid container field effect transistor ph sensor with interdigital micro trench for liquid ion testing is presented. Growth morphology and ph sensing property of continuous few-layer graphene (FLG) and quasi-continuous monolayer graphene (MG) channels are compared. The experiment results show that the source-to-drain current of the graphene channel FET has a significant and fast response after adsorption of the measured molecule and ion at the room temperature; at the same time, the FLG response time is less than 4 s. The resolution of MG (0.01) on ph value is one order of magnitude higher than that of FLG (0.1). The reason is that with fewer defects, the MG is more likely to adsorb measured molecule and ion, and the molecules and ions can make the transport property change. The output sensitivities of MG are from 34.5% to 57.4% when the ph value is between 7 and 8, while sensitivity of FLG is 4.75% when the Ph=6. The sensor fabrication combines traditional silicon technique and flexible electronic technology and provides an easy way to develop graphene-based electrolyte gas sensor or even biological sensors.

  13. Alkaline pH sensor molecules.

    Science.gov (United States)

    Murayama, Takashi; Maruyama, Ichiro N

    2015-11-01

    Animals can survive only within a narrow pH range. This requires continual monitoring of environmental and body-fluid pH. Although a variety of acidic pH sensor molecules have been reported, alkaline pH sensor function is not well understood. This Review describes neuronal alkaline pH sensors, grouped according to whether they monitor extracellular or intracellular alkaline pH. Extracellular sensors include the receptor-type guanylyl cyclase, the insulin receptor-related receptor, ligand-gated Cl- channels, connexin hemichannels, two-pore-domain K+ channels, and transient receptor potential (TRP) channels. Intracellular sensors include TRP channels and gap junction channels. Identification of molecular mechanisms underlying alkaline pH sensing is crucial for understanding how animals respond to environmental alkaline pH and how body-fluid pH is maintained within a narrow range. © 2015 Wiley Periodicals, Inc.

  14. Potassium transport of Salmonella is important for type III secretion and pathogenesis

    Science.gov (United States)

    Liu, Yehao; Ho, Katharina Kim; Su, Jing; Gong, Hao; Chang, Alexander C.

    2013-01-01

    Intracellular cations are essential for the physiology of all living organisms including bacteria. Cations such as potassium ion (K+), sodium ion (Na+) and proton (H+) are involved in nearly all aspects of bacterial growth and survival. K+ is the most abundant cation and its homeostasis in Escherichia coli and Salmonella is regulated by three major K+ transporters: high affinity transporter Kdp and low affinity transporters Kup and Trk. Previous studies have demonstrated the roles of cations and cation transport in the physiology of Escherichia coli; their roles in the virulence and physiology of pathogenic bacteria are not well characterized. We have previously reported that the Salmonella K+ transporter Trk is important for the secretion of effector proteins of the type III secretion system (TTSS) of Salmonella pathogenicity island 1 (SPI-1). Here we further explore the role of Salmonella cation transport in virulence in vitro and pathogenesis in animal models. Impairment of K+ transport through deletion of K+ transporters or exposure to the chemical modulators of cation transport, gramicidin and valinomycin, results in a severe defect in the TTSS of SPI-1, and this defect in the TTSS was not due to a failure to regulate intrabacterial pH or ATP. Our results also show that K+ transporters are critical to the pathogenesis of Salmonella in mice and chicks and are involved in multiple growth and virulence characteristics in vitro, including protein secretion, motility and invasion of epithelial cells. These results suggest that cation transport of the pathogenic bacterium Salmonella, especially K+ transport, contributes to its virulence in addition to previously characterized roles in maintaining homeostasis of bacteria. PMID:23728623

  15. Scintillation light transport and detection

    International Nuclear Information System (INIS)

    Gabriel, T.A.; Lillie, R.A.

    1986-08-01

    The MORSE neutron gamma-ray transport code has been modified to allow for the transport of scintillation light. This modified code is used to analyze the light collection characteristics of a large liquid scintillator module (18 x 18 x 350 cm 3 )

  16. Histone deacetylase-mediated regulation of endolysosomal pH.

    Science.gov (United States)

    Prasad, Hari; Rao, Rajini

    2018-05-04

    The pH of the endolysosomal system is tightly regulated by a balance of proton pump and leak mechanisms that are critical for storage, recycling, turnover, and signaling functions in the cell. Dysregulation of endolysosomal pH has been linked to aging, amyloidogenesis, synaptic dysfunction, and various neurodegenerative disorders, including Alzheimer's disease. Therefore, understanding the mechanisms that regulate luminal pH may be key to identifying new targets for managing these disorders. Meta-analysis of yeast microarray databases revealed that nutrient-limiting conditions inhibited the histone deacetylase (HDAC) Rpd3 and thereby up-regulated transcription of the endosomal Na + /H + exchanger Nhx1, resulting in vacuolar alkalinization. Consistent with these findings, Rpd3 inhibition by the HDAC inhibitor and antifungal drug trichostatin A induced Nhx1 expression and vacuolar alkalinization. Bioinformatics analysis of Drosophila and mouse databases revealed that caloric control of the Nhx1 orthologs DmNHE3 and NHE6, respectively, is also mediated by HDACs. We show that NHE6 is a target of the transcription factor cAMP-response element-binding protein (CREB), a known regulator of cellular responses to low-nutrient conditions, providing a molecular mechanism for nutrient- and HDAC-dependent regulation of endosomal pH. Of note, pharmacological targeting of the CREB pathway to increase NHE6 expression helped regulate endosomal pH and correct defective clearance of amyloid Aβ in an apoE4 astrocyte model of Alzheimer's disease. These observations from yeast, fly, mouse, and cell culture models point to an evolutionarily conserved mechanism for HDAC-mediated regulation of endosomal NHE expression. Our insights offer new therapeutic strategies for modulation of endolysosomal pH in fungal infection and human disease. © 2018 Prasad and Rao.

  17. Signed Young Modules and Simple Specht Modules

    OpenAIRE

    Danz, Susanne; Lim, Kay Jin

    2015-01-01

    By a result of Hemmer, every simple Specht module of a finite symmetric group over a field of odd characteristic is a signed Young module. While Specht modules are parametrized by partitions, indecomposable signed Young modules are parametrized by certain pairs of partitions. The main result of this article establishes the signed Young module labels of simple Specht modules. Along the way we prove a number of results concerning indecomposable signed Young modules that are of independent inter...

  18. Fetal scalp pH testing

    Science.gov (United States)

    Fetal scalp blood; Scalp pH testing; Fetal blood testing - scalp; Fetal distress - fetal scalp testing; Labor - fetal scalp testing ... a baby. In these cases, testing the scalp pH can help the doctor decide whether the fetus ...

  19. Acid loading test (pH)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003615.htm Acid loading test (pH) To use the sharing features on this page, please enable JavaScript. The acid loading test (pH) measures the ability of the ...

  20. Memory Modulation

    NARCIS (Netherlands)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive

  1. Module descriptor

    DEFF Research Database (Denmark)

    Vincenti, Gordon; Klausen, Bodil; Kjær Jensen, Jesper

    2016-01-01

    The Module Descriptor including a Teacher’s Guide explains and describes how to work innovatively and co-creatively with wicked problems and young people. The descriptor shows how interested educators and lecturers in Europe can copy the lessons of the Erasmus+ project HIP when teaching their own...

  2. Biona-C Cell Culture pH Monitoring System

    Science.gov (United States)

    Friedericks, C.

    1999-01-01

    Sensors 2000! is developing a system to demonstrate the ability to perform accurate, real-time measurements of pH and CO2 in a cell culture media in Space. The BIONA-C Cell Culture pH Monitoring System consists of S2K! developed ion selective sensors and control electronics integrated with the fluidics of a cell culture system. The integrated system comprises a "rail" in the Cell Culture Module (CCM) of WRAIR (Space Biosciences of Walter Read Army Institute of Research). The CCM is a Space Shuttle mid-deck locker experiment payload. The BIONA-C is displayed along with associated graphics and text explanations. The presentation will stimulate interest in development of sensor technology for real-time cell culture measurements. The transfer of this technology to other applications will also be of interest. Additional information is contained in the original document.

  3. Ca2+-associated triphasic pH changes in mitochondria during brown adipocyte activation.

    Science.gov (United States)

    Hou, Yanyan; Kitaguchi, Tetsuya; Kriszt, Rókus; Tseng, Yu-Hua; Raghunath, Michael; Suzuki, Madoka

    2017-08-01

    Brown adipocytes (BAs) are endowed with a high metabolic capacity for energy expenditure due to their high mitochondria content. While mitochondrial pH is dynamically regulated in response to stimulation and, in return, affects various metabolic processes, how mitochondrial pH is regulated during adrenergic stimulation-induced thermogenesis is unknown. We aimed to reveal the spatial and temporal dynamics of mitochondrial pH in stimulated BAs and the mechanisms behind the dynamic pH changes. A mitochondrial targeted pH-sensitive protein, mito-pHluorin, was constructed and transfected to BAs. Transfected BAs were stimulated by an adrenergic agonist, isoproterenol. The pH changes in mitochondria were characterized by dual-color imaging with indicators that monitor mitochondrial membrane potential and heat production. The mechanisms of pH changes were studied by examining the involvement of electron transport chain (ETC) activity and Ca 2+ profiles in mitochondria and the intracellular Ca 2+ store, the endoplasmic reticulum (ER). A triphasic mitochondrial pH change in BAs upon adrenergic stimulation was revealed. In comparison to a thermosensitive dye, we reveal that phases 1 and 2 of the pH increase precede thermogenesis, while phase 3, characterized by a pH decrease, occurs during thermogenesis. The mechanism of pH increase is partially related to ETC. In addition, the pH increase occurs concurrently with an increase in mitochondrial Ca 2+ . This Ca 2+ increase is contributed to by an influx from the ER, and it is further involved in mitochondrial pH regulation. We demonstrate that an increase in mitochondrial pH is implicated as an early event in adrenergically stimulated BAs. We further suggest that this pH increase may play a role in the potentiation of thermogenesis.

  4. pH sensor calibration procedure

    OpenAIRE

    Artero Delgado, Carola; Nogueras Cervera, Marc; Manuel Lázaro, Antonio; Prat Tasias, Jordi; Prat Farran, Joana d'Arc

    2013-01-01

    This paper describes the calibration of pH sensor located at the OBSEA marine Observatory. This instrument is based on an industrial pH electrode that is connected to a CTD instrument (Conductivity, Temperature, and Depth ). The calibration of the pH sensor has been done using a high precision spectrophotometer pH meter from Institute of Marine Sciences (ICM), and in this way it has been obtained a numerical function for the p H sensor propor...

  5. PhD students and integrative research

    NARCIS (Netherlands)

    Fry, G.; Tress, B.; Tress, G.

    2006-01-01

    The training of PhD students is currently very dynamic and varies widely from place to place. We present some examples of this variation and comment on how it may affect the way PhD students cope with integrative studies. Our focus is on the training needs of PhD students studying integrative

  6. Dynamic regulation of gastric surface pH by luminal pH

    OpenAIRE

    Chu, Shaoyou; Tanaka, Shin; Kaunitz, Jonathan D.; Montrose, Marshall H.

    1999-01-01

    In vivo confocal imaging of the mucosal surface of rat stomach was used to measure pH noninvasively under the mucus gel layer while simultaneously imaging mucus gel thickness and tissue architecture. When tissue was superfused at pH 3, the 25 μm adjacent to the epithelial surface was relatively alkaline (pH 4.1 ± 0.1), and surface alkalinity was enhanced by topical dimethyl prostaglandin E2 (pH 4.8 ± 0.2). Luminal pH was changed from pH 3 to pH 5 to mimic the fasted-to-fed transition in intra...

  7. Global model structures for ∗-modules

    DEFF Research Database (Denmark)

    Böhme, Benjamin

    2018-01-01

    We extend Schwede's work on the unstable global homotopy theory of orthogonal spaces and L-spaces to the category of ∗-modules (i.e., unstable S-modules). We prove a theorem which transports model structures and their properties from L-spaces to ∗-modules and show that the resulting global model...... structure for ∗-modules is monoidally Quillen equivalent to that of orthogonal spaces. As a consequence, there are induced Quillen equivalences between the associated model categories of monoids, which identify equivalent models for the global homotopy theory of A∞-spaces....

  8. Radiation Transport

    Energy Technology Data Exchange (ETDEWEB)

    Urbatsch, Todd James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-06-15

    We present an overview of radiation transport, covering terminology, blackbody raditation, opacities, Boltzmann transport theory, approximations to the transport equation. Next we introduce several transport methods. We present a section on Caseology, observing transport boundary layers. We briefly broach topics of software development, including verification and validation, and we close with a section on high energy-density experiments that highlight and support radiation transport.

  9. Highly Sensitive and Wide-Dynamic-Range Multichannel Optical-Fiber pH Sensor Based on PWM Technique

    OpenAIRE

    Md. Rajibur Rahaman Khan; Shin-Won Kang

    2016-01-01

    In this study, we propose a highly sensitive multichannel pH sensor that is based on an optical-fiber pulse width modulation (PWM) technique. According to the optical-fiber PWM method, the received sensing signal?s pulse width changes when the optical-fiber pH sensing-element of the array comes into contact with pH buffer solutions. The proposed optical-fiber PWM pH-sensing system offers a linear sensing response over a wide range of pH values from 2 to 12, with a high pH-sensing ability. The...

  10. Novel functions of CCM1 delimit the relationship of PTB/PH domains.

    Science.gov (United States)

    Zhang, Jun; Dubey, Pallavi; Padarti, Akhil; Zhang, Aileen; Patel, Rinkal; Patel, Vipulkumar; Cistola, David; Badr, Ahmed

    2017-10-01

    Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH) domains were recognized as structurally related but functionally distinct domains. By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, PH and FERM domain(s). We identified a group of 28 novel cellular partners of CCM1, all of which contain either PTB or PH domain(s), and developed a novel classification system for these PTB/PH proteins based on their relationship with different NPXY motifs of CCM1. Our results demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH proteins and perpetuates their specificity to interact with certain PTB/PH domains through selective combination of three NPXY motifs. We also demonstrated that CCM1 can be assembled into oligomers through intermolecular interaction between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH domain to interact with NPXY motif. The most salient feature of the study was that both PTB and PH domains are structurally and functionally comparable, suggesting that PTB domain is likely evolved from PH domain with polymorphic structural additions at its N-terminus. A new β1A-strand of the PTB domain was discovered and new minimum structural requirement of PTB/PH domain for NPXY motif-binding was determined. Based on our data, a novel theory of structure, function and

  11. Effect of rhizosphere pH condition on cadmium movement in a soybean plant

    International Nuclear Information System (INIS)

    Ohya, T.; Tanoi, K.; Iikura, H.; Rai, H.; Nakanishi, T.M.

    2008-01-01

    To study the effect of rhizosphere pH condition on the cadmium uptake movement, 109 Cd, was applied as a radioisotope tracer to a soybean plant grown in a water culture at pH 4.5 or pH 6.5. The distribution of 109 Cd in the soybean plant was observed radiographically with an imaging plate (IP). The amount of Cd transported from the root to the upper part of the plant at pH 4.5 was approximately two times higher than that at pH 6.5. However, the movement of Cd in the upper part of the plant was similar under both pH conditions. The distribution of Cd inside the internodes at pH 4.5 also showed similar pattern to that at pH 6.5, suggesting that once Cd reached to the vessel of the root, the movement of Cd was not dependent on rhizosphere pH conditions. (author)

  12. pH control structure design for a periodically operated membrane separation process

    DEFF Research Database (Denmark)

    Prado Rubio, Oscar Andres; Jørgensen, Sten Bay; Jonsson, Gunnar Eigil

    2012-01-01

    A bioreactor integrated with an electrically driven membrane separation process (Reverse Electro-Enhanced Dialysis – REED) is under investigation as potential technology for intensifying lactic acid bioproduction. In this contribution the pH regulation issue in the periodically operated REED module...

  13. Chamber transport

    International Nuclear Information System (INIS)

    Olson, Craig L.

    2001-01-01

    Heavy ion beam transport through the containment chamber plays a crucial role in all heavy ion fusion (HIF) scenarios. Here, several parameters are used to characterize the operating space for HIF beams; transport modes are assessed in relation to evolving target/accelerator requirements; results of recent relevant experiments and simulations of HIF transport are summarized; and relevant instabilities are reviewed. All transport options still exist, including (1) vacuum ballistic transport, (2) neutralized ballistic transport, and (3) channel-like transport. Presently, the European HIF program favors vacuum ballistic transport, while the US HIF program favors neutralized ballistic transport with channel-like transport as an alternate approach. Further transport research is needed to clearly guide selection of the most attractive, integrated HIF system

  14. Measurements of spectral responses for developing fiber-optic pH sensor

    Science.gov (United States)

    Yoo, Wook Jae; Heo, Ji Yeon; Jang, Kyoung Won; Seo, Jeong Ki; Moon, Jin Soo; Park, Jang-Yeon; Park, Byung Gi; Cho, Seunghyun; Lee, Bongsoo

    2011-01-01

    In this study, we have fabricated a fiber-optic pH sensor, which is composed of a light source, a pH-sensing probe, plastic optical fibers and a spectrometer, for determining the degree of infection by Helicobacter pylori in the stomach. As pH indicators, phenol red and m-cresol purple are used, and pH liquid solutions are prepared by mixing phenol red or m-cresol purple solutions and various kinds of pH buffer solutions. The light emitted by a light source is guided by plastic optical fibers to the pH liquid solution, and the optical characteristic of a reflected light is changed according to the color variations of the pH indicator in the pH-sensing probe. Therefore, we have measured the intensities and wavelength shifts of the reflected lights, which change according to the color variations of indicators at different pH values, by using a spectrometer for spectral analysis. Also, the relationships between the pH values of liquid solutions and the optical properties of the modulated lights are obtained on the basis of the changes of the colors of indicators.

  15. Salivary pH as a marker of plasma adiponectin concentrations in Women.

    Science.gov (United States)

    Tremblay, Monique; Loucif, Yacine; Methot, Julie; Brisson, Diane; Gaudet, Daniel

    2012-02-03

    Plasma adiponectin is a significant correlate of the pro-inflammatory cardiometabolic risk profile associated with obesity and type 2 diabetes. Salivary pH is influenced by several cardiometabolic risk components such as inflammation, oxidation and numerous oral and systemic health modulators, including the menopausal status. This study aimed to assess the association between plasma adiponectin concentrations and salivary pH in women according to the menopausal status. Unstimulated saliva collection was performed in 151 Caucasian women of French-Canadian origin (53 premenopausal women (PMW) and 98 menopausal women (MW)). Student's t test, ANOVA and linear regression models were used to assess the association between plasma adiponectin concentrations and salivary pH. Plasma adiponectin levels increased as a function of salivary pH in the whole sample and among MW (r = 0.29 and r = 0.36, p salivary pH (R2) was 10.8% (p salivary pH quartiles (p = 0.005). These results suggest that salivary pH is a significant correlate of plasma adiponectin levels in women. With the increasing prevalence of type 2 diabetes and obesity, new technologies should be developed to more easily monitor health status, disease onset and progression. Salivary pH, a simple, inexpensive and non-invasive measure, could be a very promising avenue.

  16. Parathyroid hormone depresses cytosolic pH and DNA synthesis in osteoblast-like cells

    International Nuclear Information System (INIS)

    Reid, I.R.; Civitelli, R.; Avioli, L.V.; Hruska, K.A.

    1988-01-01

    It has recently become apparent that a number of hormones and growth factors modulate cytosolic pH (pH i ) and there is some evidence that this in turn may influence cell growth. The authors have examined the effects of parathyroid hormone (PTH) on both these parameters in an osteoblast-like cell line, UMR 106. Preliminary studies, using the pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5,(6)-carboxyfluorescein indicated that these cells regulate pH i by means of an amiloride-inhibitable Na + -H + exchanger. Rat PTH-(1-34) (rPTH) caused a progressive dose-related decrease in pH i with a half-maximal effect at 10 -11 M. The diacylglycerol analogue, phorbol 12-myristate 13-acetate, increased both pH i and [ 3 H]thymidine incorporation, and amiloride reduced both indexes. However, rPTH remained a potent inhibitor of [ 3 H]thymidine incorporation in the presence of amiloride, even though it did not affect pH i in these circumstances. It is concluded that PTH decreases pH i and growth in UMR 106 cells but that these changes can be dissociated. Depression of pH i may have other important effects on bone metabolism, such as reducing cell-cell communication, and may be associated with alkalinization of the bone fluid compartment

  17. Regulation of Vacuolar pH in Citrus limon

    Energy Technology Data Exchange (ETDEWEB)

    Lincoln Taiz

    2005-06-22

    The primary objective of this grant was to characterize the vacuolar V-ATPase of lemon fruits. Lemon fruit vacuoles have an internal pH of about 2.5. Since a typical plant vacuole has a luminal pH of around 5.5, the lemon fruit V-APTase must have special properties which allow it to acidify the lumen to such a low pH: (1) it might have a different structure; (2) it might have a different H{sup +}/ATP stoichiometry; and (3) it might be regulated differently. During the course of the investigations (which began in 1996) they characterized these aspects of the V-ATPases of both lemon fruits and lime fruits. They examined lime fruits because of the availability of both acidic limes with a low vacuolar pH and sweet limes, which have a much higher vacuolar pH. The existence of two types of lime fruits allowed a comparison of the V-ATPases of the two varieties. In this report they are including two publications from 1996 and 1997 as background for the later publications. A review article with Heven Sze on V-ATPase nomenclature was also generated during the funding period. In addition to the studies on citrus fruit vacuoles, they also initiated studies in two new areas: polar auxin transport and the regulation of stomatal opening by UV-B irradiation. These studies were intended to serve as a basis of future separate grants, but the proposals they submitted on these topics were not funded.

  18. Regulation of arsenic mobility on basaltic glass surfaces by speciation and pH.

    Science.gov (United States)

    Sigfusson, Bergur; Meharg, Andrew A; Gislason, Sigurdur R

    2008-12-01

    The importance of geothermal energy as a source for electricity generation and district heating has increased over recent decades. Arsenic can be a significant constituent of the geothermal fluids pumped to the surface during power generation. Dissolved As exists in different oxidation states, mainly as As(III) and As(V), and the charge of individual species varies with pH. Basaltic glass is one of the most important rock types in many high-temperature geothermal fields. Static batch and dynamic column experiments were combined to generate and validate sorption coefficients for As(III) and As(V) in contact with basaltic glass at pH 3-10. Validation was carried out by two empirical kinetic models and a surface complexation model (SCM). The SCM provided a better fit to the experimental column data than kinetic models at high pH values. However, in certain circumstances, an adequate estimation of As transport in the column could not be attained without incorporation of kinetic reactions. The varying mobility with pH was due to the combined effects of the variable charge of the basaltic glass with the pH point of zero charge at 6.8 and the individual As species as pH shifted, respectively. The mobility of As(III) decreased with increasing pH. The opposite was true for As(V), being nearly immobile at pH 3 to being highly mobile at pH 10. Incorporation of appropriate sorption constants, based on the measured pH and Eh of geothermal fluids, into regional groundwater-flow models should allow prediction of the As(III) and As(V) transport from geothermal systems to adjacent drinking water sources and ecosystems.

  19. pH distribution in human tumors

    International Nuclear Information System (INIS)

    Thistlethwaite, A.J.; Leeper, D.B.; Moylan, D.J.; Nerlinger, R.E.

    1984-01-01

    pH distribution in human tumors is being determined to evaluate this parameter as a prognostic indicator of hyperthermia response. pH is measured by a modified glass pH electrode (21g, model MI 408, Microelectrodes, Inc., Londonderry, NH) inserted through an 18g open-ended Angiocath. Eight tumors have been evaluated to date; and of those, 3 were also assayed after the first heat treatment coincident with determination of blood flow. Tumors were between 2-5 cm, of various histologies, and of primary, recurrent, or metastatic origin. 2-4 measurements were made per tumor. Pretreatment readings were between 6.4 and 7.2 pH units. As tumor blood flow increased after 1 hr heating (41.5 - 43 0 ) pH rose 0.1 - 0.3 units. Normal rat muscle yields pH readings of 7.35 - 7.45. Although there was considerable heterogeneity of pH within tumors, accuracy and drift were not a problem. 5-15 min were required for pH stabilization after catheter insertion and <5 min after electrode insertion. A saline wheal was used for anesthesia to preclude modification of pH by anesthetics. Patient tolerance has not been a problems. This study suggests that human tumor tissue has a preponderance of areas more acidic than normal tissue. This may serve to sensitize tumor cells to hyperthermia and provide a prognostic indicator of tumor response

  20. Induction accelerator test module for HIF

    International Nuclear Information System (INIS)

    Faltens, A.

    1991-04-01

    An induction linac test module suitable for investigating the drive requirements and the longitudinal coupling impedance of a high-power ion induction linac has been constructed by the Heavy Ion Fusion (HIF) group at LBL. The induction linac heavy ion driver for inertial confinement fusion (ICF) as presently envisioned uses multiple parallel beams which are transported in separate focusing channels but accelerated together in the induction modules. The resulting induction modules consequently have large beam apertures-1--2 meters in diameter- and correspondingly large outside diameters. The module geometry is related to a low-frequency ''gap capacity'' and high-frequency structural resonances, which are affected by the magnetic core loading and the module pulser impedance. A description of the test module and preliminary results are presented. 3 figs

  1. Development of GREET Catalyst Module

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhichao [Argonne National Lab. (ANL), Argonne, IL (United States); Benavides, Pahola T. [Argonne National Lab. (ANL), Argonne, IL (United States); Dunn, Jennifer B. [Argonne National Lab. (ANL), Argonne, IL (United States); Cronauer, Donald C. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-09-01

    In this report, we develop energy and material flows for the production of five different catalysts (tar reforming, alcohol synthesis, Zeolite Socony Mobil-5 [ZSM-5], Mo/Co/ γ-Al2O3, and Pt/ γ-Al2O3) and two chemicals (olivine, dimethyl ether of polyethylene glycol [DEPG]). These compounds and catalysts are now included in the Greenhouse Gases, Regulated Emissions and Energy Use in Transportation (GREET™) catalyst module.

  2. Unity connecting module in SSPF

    Science.gov (United States)

    1998-01-01

    In the Space Station Processing Facility, the Unity connecting module, part of the International Space Station, is shown with Pressurized Mating Adapters 1 (left) and 2 (right) attached. Unity is scheduled to undergo testing of the common berthing mechanism to which other space station elements will dock. Unity is the primary payload on mission STS-88, targeted to launch Dec. 3, 1998. Other testing includes the Pad Demonstration Test to verify the compatibility of the module with the Space Shuttle as well as the ability of the astronauts to send and receive commands to Unity from the flight deck of the orbiter. Unity is expected to be ready for installation into the payload canister on Oct. 25, and transported to Launch Pad 39-A on Oct. 27. The Unity will be mated to the Russian-built Zarya control module which should already be in orbit at that time.

  3. Solid-state membrane module

    Science.gov (United States)

    Gordon, John Howard [Salt Lake City, UT; Taylor, Dale M [Murray, UT

    2011-06-07

    Solid-state membrane modules comprising at least one membrane unit, where the membrane unit has a dense mixed conducting oxide layer, and at least one conduit or manifold wherein the conduit or manifold comprises a dense layer and at least one of a porous layer and a slotted layer contiguous with the dense layer. The solid-state membrane modules may be used to carry out a variety of processes including the separating of any ionizable component from a feedstream wherein such ionizable component is capable of being transported through a dense mixed conducting oxide layer of the membrane units making up the membrane modules. For ease of construction, the membrane units may be planar.

  4. Interfacial reactions in thermoelectric modules

    KAUST Repository

    Wu, Hsin-jay

    2018-02-21

    Engineering transport properties of thermoelectric (TE) materials leads to incessantly breakthroughs in the zT values. Nevertheless, modular design holds a key factor to advance the TE technology. Herein, we discuss the structures of TE module and illustrate the inter-diffusions across the interface of constituent layers. For Bi2Te3-based module, soldering is the primary bonding method, giving rise to the investigations on the selections of solder, diffusion barrier layer and electrode. For mid-temperature PbTe-based TE module, hot-pressing or spark plasma sintering are alternative bonding approaches; the inter-diffusions between the diffusion barrier layer, electrode and TE substrate are addressed as well.

  5. Modeling electrokinetic transport in phenol contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Zorn, R.; Haus, R.; Czurda, K. [Dept. of Applied Geology, Univ. Karlsruhe (Germany)

    2001-07-01

    Numerical simulations are compared to laboratory experiments of electroremediation in soils contaminated by phenolic pollutants. The developing pH affects the electrokinetic transport behaviour of phenol. It is found that a water chemistry model must be included in an electrokinetic mass transport model to describe the process of electroremediation more accurately, if no buffering system is used at the electrodes. In the case of controlling the pH at the electrode compartments only a simplified chemical reaction model must be included in the numerical code to match the experimental phenolic transport. (orig.)

  6. MEMORY MODULATION

    Science.gov (United States)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

  7. A microfabricated fringing field capacitive pH sensor with an integrated readout circuit

    Energy Technology Data Exchange (ETDEWEB)

    Arefin, Md Shamsul, E-mail: md.arefin@monash.edu; Redoute, Jean-Michel; Rasit Yuce, Mehmet [Electrical and Computer Systems Engineering, Monash University, Melbourne (Australia); Bulut Coskun, M.; Alan, Tuncay; Neild, Adrian [Mechanical and Aerospace Engineering, Monash University, Melbourne (Australia)

    2014-06-02

    This work presents a microfabricated fringe-field capacitive pH sensor using interdigitated electrodes and an integrated modulation-based readout circuit. The changes in capacitance of the sensor result from the permittivity changes due to pH variations and are converted to frequency shifts using a crossed-coupled voltage controlled oscillator readout circuit. The shift in resonant frequency of the readout circuit is 30.96 MHz for a change in pH of 1.0–5.0. The sensor can be used for the measurement of low pH levels, such as gastric acid, and can be integrated with electronic pills. The measurement results show high repeatability, low noise, and a stable output.

  8. A microfabricated fringing field capacitive pH sensor with an integrated readout circuit

    International Nuclear Information System (INIS)

    Arefin, Md Shamsul; Redoute, Jean-Michel; Rasit Yuce, Mehmet; Bulut Coskun, M.; Alan, Tuncay; Neild, Adrian

    2014-01-01

    This work presents a microfabricated fringe-field capacitive pH sensor using interdigitated electrodes and an integrated modulation-based readout circuit. The changes in capacitance of the sensor result from the permittivity changes due to pH variations and are converted to frequency shifts using a crossed-coupled voltage controlled oscillator readout circuit. The shift in resonant frequency of the readout circuit is 30.96 MHz for a change in pH of 1.0–5.0. The sensor can be used for the measurement of low pH levels, such as gastric acid, and can be integrated with electronic pills. The measurement results show high repeatability, low noise, and a stable output.

  9. Hydrogel-coated fiber Bragg grating sensor for pH monitoring

    Science.gov (United States)

    Pabbisetti, Vayu Nandana Kishore; Madhuvarasu, Sai Shankar

    2016-06-01

    We present a fiber-optic wavelength-modulated sensor for pH applications. Fiber Bragg grating (FBG) is functionalized with a stimulus-responsive hydrogel that induces a strain on FBG due to mechanical expansion of the gel in response to ambient pH changes. The gel is synthesized from the blends of poly (vinyl alcohol)/poly (acrylic acid). The induced strain results in a shift of FBG reflected peak that is monitored by an interrogator. The sensor system shows good linearity in the acidic pH range of 3 to 7 with a sensitivity of 12.16 pm/pH. In addition, it shows good repeatability and oscillator behavior, which proves it to be fit for pH sensing applications.

  10. Coaching af ph.d.-studerende

    DEFF Research Database (Denmark)

    Godskesen, Mirjam Irene

    Rapporten danner grundlag for at etablere et koncept for ph.d.-coaching. Erfaringerne fra et 2-årigt projekt om ph.d.-coaching i SCKK regi beskrives. De centrale temaer er tilrettelæggelse af den individuelle coaching, typiske temaer i coachingen og arbejdsdeling mellem coach og vejleder. Der er...

  11. Salivary pH: A diagnostic biomarker

    Directory of Open Access Journals (Sweden)

    Sharmila Baliga

    2013-01-01

    Full Text Available Objectives: Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. Study Design: The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. Results: The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001 whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001. Conclusion: These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.

  12. Salivary pH: A diagnostic biomarker.

    Science.gov (United States)

    Baliga, Sharmila; Muglikar, Sangeeta; Kale, Rahul

    2013-07-01

    Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001) whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001). These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.

  13. Ph og børnenes rum

    DEFF Research Database (Denmark)

    de Coninck-Smith, Ning

    2008-01-01

    Arkiteten og kulturkritikeren PH tegnede to bygninger til børn, nemlig fabriksbørnehaven ved Dehns Vaskeri fra 1948 og det ombyggede børnehjem Mindet fra 1954. Bidraget diskuterer PH's særlige greb om arkitektur til børn og placerer det ind i samtidens diskussion om børn, deres udvikling og behov....

  14. PER PhDs & Bachelor's Degrees

    Science.gov (United States)

    White, Susan C.

    2017-01-01

    Recently, the editor remarked to me that physics departments that offered a PhD with a specialization in Physics Education Research (PER) seemed to graduate more bachelor's degree recipients than those physics PhD departments that did not have the specialization. I was not convinced. That led to quite a bit of discussion between us. He compiled a…

  15. Urbanism PhD Research 2008 - 2010

    NARCIS (Netherlands)

    Smit, M.; Van der Hoeven, F.D.; Brand, N.; Van der Burg, L.; Çal??kan, O.; Tan, E.R.; Wang, C.Y.; Zhou, J.

    2009-01-01

    To ensure the quality of the Ph.D. research the Department introduced a special procedure for periodic evaluation: after a period of nine months the potential Ph.D. candidates are asked to present their research design, theoretical framework and methodological approach to the members of the

  16. (ajst) the influence of ph and adsorbent

    African Journals Online (AJOL)

    goethite sorbed a little more metal ion than the natural goethite. This was attributed ... was greatly governed by pH with nearly 100% adsorption of Pb occurring at initial pH of 5. Generally, Pb was ... extensively study and applied for the removal of heavy .... Goethite has variable surface charge characteristics, which gave it a ...

  17. On Calibration of pH Meters

    Directory of Open Access Journals (Sweden)

    Da-Ming Zhu

    2005-04-01

    Full Text Available The calibration of pH meters including the pH glass electrode, ISE electrodes,buffers, and the general background for calibration are reviewed. Understanding of basicconcepts of pH, pOH, and electrode mechanism is emphasized. New concepts of pH, pOH,as well as critical examination of activity, and activity coefficients are given. Theemergence of new solid state pH electrodes and replacement of the salt bridge with aconducting wire have opened up a new horizon for pH measurements. A pH buffer solutionwith a conducting wire may be used as a stable reference electrode. The misleadingunlimited linear Nernstian slope should be discarded. Calibration curves with 3 nonlinearportions for the entire 0—14 pH range due to the isoelectric point change effect areexplained. The potential measurement with stirring or unstirring and effects by double layer(DL and triple layer (TL will be discussed.

  18. Spectroscopic determination of pH

    International Nuclear Information System (INIS)

    Faanu, A.; Glover, E.T.; Bailey, E.; Rochelle, C.

    2009-01-01

    A technique of measuring pH at temperature range of 20 - 70 0 C and high pressure conditions of 1 - 200 atmospheres has been developed by relating the ratio of absorbance peaks of indicator solutions (basic and acidic) as a function of pH, using ultraviolet-visible spectrophotometer. The pH values of the buffer solutions measured at 20 0 C and 70 0 C indicated slight temperature dependence, while the pressure had no effect. The pH of the buffer solutions increased with temperature with relative standard deviations in the range 0.4 - 0.5 % at 95 % confidence interval. The possible causes of the temperature dependence were attributed to changes in pH values as the temperature changed. (au)

  19. Determination Of Ph Including Hemoglobin Correction

    Science.gov (United States)

    Maynard, John D.; Hendee, Shonn P.; Rohrscheib, Mark R.; Nunez, David; Alam, M. Kathleen; Franke, James E.; Kemeny, Gabor J.

    2005-09-13

    Methods and apparatuses of determining the pH of a sample. A method can comprise determining an infrared spectrum of the sample, and determining the hemoglobin concentration of the sample. The hemoglobin concentration and the infrared spectrum can then be used to determine the pH of the sample. In some embodiments, the hemoglobin concentration can be used to select an model relating infrared spectra to pH that is applicable at the determined hemoglobin concentration. In other embodiments, a model relating hemoglobin concentration and infrared spectra to pH can be used. An apparatus according to the present invention can comprise an illumination system, adapted to supply radiation to a sample; a collection system, adapted to collect radiation expressed from the sample responsive to the incident radiation; and an analysis system, adapted to relate information about the incident radiation, the expressed radiation, and the hemoglobin concentration of the sample to pH.

  20. Endoscopic sensing of alveolar pH.

    Science.gov (United States)

    Choudhury, D; Tanner, M G; McAughtrie, S; Yu, F; Mills, B; Choudhary, T R; Seth, S; Craven, T H; Stone, J M; Mati, I K; Campbell, C J; Bradley, M; Williams, C K I; Dhaliwal, K; Birks, T A; Thomson, R R

    2017-01-01

    Previously unobtainable measurements of alveolar pH were obtained using an endoscope-deployable optrode. The pH sensing was achieved using functionalized gold nanoshell sensors and surface enhanced Raman spectroscopy (SERS). The optrode consisted of an asymmetric dual-core optical fiber designed for spatially separating the optical pump delivery and signal collection, in order to circumvent the unwanted Raman signal generated within the fiber. Using this approach, we demonstrate a ~100-fold increase in SERS signal-to-fiber background ratio, and demonstrate multiple site pH sensing with a measurement accuracy of ± 0.07 pH units in the respiratory acini of an ex vivo ovine lung model. We also demonstrate that alveolar pH changes in response to ventilation.

  1. Influence of pH on the localized corrosion of iron

    International Nuclear Information System (INIS)

    Webley, R.; Henry, R.

    1986-06-01

    The influence of pH on the pitting corrosion of iron in chloride and sulfate solutions was determined using two artificial pit apparatuses to obtain the pH near the surface of the pit bottom. A glass membrane electrode and an antimony electrode were used to measure pH in the two apparatuses. Using solutions of NaCl and Na 2 SO 4 at current densities of 0.5, 5.0, and 10 mA/cm 2 pH's in the range 5 to 6 were obtained with the first apparatus. The antimony probe did not measure pH accurately in solutions of 1 N NaCl and 1 N Na 2 SO 4 and had an error of approximately 2 pH units. A one-dimensional transport model was developed to predict pH variations around the pit mouth and inside the pit. The validity of this model was not verified due to the relative lack of precision with pH measurement techniques

  2. Development of Hybrid pH sensor for long-term seawater pH monitoring.

    Science.gov (United States)

    Nakano, Y.; Egashira, T.; Miwa, T.; Kimoto, H.

    2016-02-01

    We have been developing the in situ pH sensor (Hybrid pH sensor: HpHS) for the long-term seawater pH monitoring. We are planning to provide the HpHS for researchers and environmental consultants for observation of the CCS (Carbon dioxide Capture and Storage) monitoring system, the coastal environment monitoring system (e.g. Blue Carbon) and ocean acidification. The HpHS has two types of pH sensors (i.e. potentiometric pH sensor and spectrophotometric pH sensor). The spectrophotometric pH sensor can measure pH correctly and stably, however it needs large power consumption and a lot of reagents in a long period of observation. The pH sensor used m-cresol purple (mCP) as an indicator of pH (Clayton and Byrne, 1993 and Liu et al., 2011). We can choose both coefficients before deployment. On the other hand, although the potentiometric pH sensor is low power consumption and high-speed response (within 10 seconds), drifts in the pH of the potentiometric measurements may possibly occur for a long-term observation. The HpHS can measure in situ pH correctly and stably combining advantage of both pH sensors. The HpHS consists of an aluminum pressure housing with optical cell (main unit) and an aluminum silicon-oil filled, pressure-compensated vessel containing pumps and valves (diaphragm pump and valve unit) and pressure-compensated reagents bags (pH indicator, pure water and Tris buffer or certified reference material: CRM) with an ability to resist water pressure to 3000m depth. The main unit holds system control boards, pump drivers, data storage (micro SD card), LED right source, photodiode, optical cell and pressure proof windows. The HpHS also has an aluminum pressure housing that holds a rechargeable lithium-ion battery or a lithium battery for the power supply (DC 24 V). The HpHS is correcting the value of the potentiometric pH sensor (measuring frequently) by the value of the spectrophotometric pH sensor (measuring less frequently). It is possible to calibrate in

  3. Transport phenomena

    International Nuclear Information System (INIS)

    Kirczenow, G.; Marro, J.

    1974-01-01

    Some simple remarks on the basis of transport theory. - Entropy, dynamics and scattering theory. - Response, relaxation and fluctuation. - Fluctuating hydrodynamics and renormalization of susceptibilities and transport coefficients. - Irreversibility of the transport equations. - Ergodic theory and statistical mechanics. - Correlation functions in Heisenberg magnets. - On the Enskog hard-sphere kinetic eqquation and the transport phenomena of dense simple gases. - What can one learn from Lorentz models. - Conductivity in a magnetic field. - Transport properties in gases in presence of external fields. - Transport properties of dilute gases with internal structure. (orig.) [de

  4. Gas puff modulation experiments in Tore Supra

    International Nuclear Information System (INIS)

    Haas, J.C.M. de; Devynck, P.; Dudok de Wit, T.; Garbet, X.; Gil, C.; Harris, G.; Laviron, C.; Martin, G.

    1993-01-01

    Experiments with a modulation of the gas puff have been done in Tore Supra with the aim to investigate the transport of particles and heat. The target plasma is ohmically heated, sawtoothing with frequencies between 12 and 20 Hz, deuterium for both the plasma and the injection, and with various densities, rising in a series of shots. Both the diffusion coefficient and the pinch velocity for the particle transport were determined using an harmonic modulation. The method gives reasonable results, even for small perturbations, and the obtained values are able to reproduce the stationary values. The heat flow carried by electrons also shows a modulation. The part of the modulation which is not caused by the density can in principle be used to discriminate diffusive and convective terms in the heat flux. An ion temperature profile calculated with empirically determined value of heat diffusivity reproduces the slow evolution of the total kinetic energy. 6 figs., 7 refs

  5. Acidic Food pH Increases Palatability and Consumption and Extends Drosophila Lifespan.

    Science.gov (United States)

    Deshpande, Sonali A; Yamada, Ryuichi; Mak, Christine M; Hunter, Brooke; Soto Obando, Alina; Hoxha, Sany; Ja, William W

    2015-12-01

    Despite the prevalent use of Drosophila as a model in studies of nutrition, the effects of fundamental food properties, such as pH, on animal health and behavior are not well known. We examined the effect of food pH on adult Drosophila lifespan, feeding behavior, and microbiota composition and tested the hypothesis that pH-mediated changes in palatability and total consumption are required for modulating longevity. We measured the effect of buffered food (pH 5, 7, or 9) on male gustatory responses (proboscis extension), total food intake, and male and female lifespan. The effect of food pH on germfree male lifespan was also assessed. Changes in fly-associated microbial composition as a result of food pH were determined by 16S ribosomal RNA gene sequencing. Male gustatory responses, total consumption, and male and female longevity were additionally measured in the taste-defective Pox neuro (Poxn) mutant and its transgenic rescue control. An acidic diet increased Drosophila gustatory responses (40-230%) and food intake (5-50%) and extended survival (10-160% longer median lifespan) compared with flies on either neutral or alkaline pH food. Alkaline food pH shifted the composition of fly-associated bacteria and resulted in greater lifespan extension (260% longer median survival) after microbes were eliminated compared with flies on an acidic (50%) or neutral (130%) diet. However, germfree flies lived longer on an acidic diet (5-20% longer median lifespan) compared with those on either neutral or alkaline pH food. Gustatory responses, total consumption, and longevity were unaffected by food pH in Poxn mutant flies. Food pH can directly influence palatability and feeding behavior and affect parameters such as microbial growth to ultimately affect Drosophila lifespan. Fundamental food properties altered by dietary or drug interventions may therefore contribute to changes in animal physiology, metabolism, and survival. © 2015 American Society for Nutrition.

  6. pH gradients in the diffusive boundary layer of subarctic macrophytes

    KAUST Repository

    Hendriks, Iris E.; Duarte, Carlos M.; Marbà , Nú ria; Krause-Jensen, Dorte

    2017-01-01

    Highly productive macrophytes produce diurnal and seasonal cycles in CO concentrations modulated by metabolic activity, which cause discrepancies between pH in the bulk water and near seaweed blades, especially when entering the diffusion boundary layer (DBL). Calcifying epiphytic organisms living in this environment are therefore exposed to a different pH environment than that of the water column. To evaluate the actual pH environment on blade surfaces, we measured the thickness of the DBL and pH gradients within it for six subarctic macrophytes: Fucus vesiculosus, Ascophyllum nodosum, Ulva lactuca, Zostera marina, Saccharina longicruris, and Agarum clathratum. We measured pH under laboratory conditions at ambient temperatures (2–3 °C) and slow, stable flow over the blade surface at five light intensities (dark, 30, 50, 100 and 200 µmol photons m s). Boundary layer thickness ranged between 511 and 1632 µm, while the maximum difference in pH (∆pH) between the blade surface and the water column ranged between 0.4 ± 0.14 (average ± SE; Zostera) and 1.2 ± 0.13 (average ± SE; Ulva) pH units. These differences in pH are larger than predictions for pH changes in the bulk water by the end of the century. A simple quadratic model best described the relationship between light intensity and maximum ∆pH, pointing at relatively low optimum PAR of between 28 and 139 µmol photons m s to reach maximum ∆pH. Elevated pH at the blade surface may provide chemical “refugia” for calcifying epiphytic organisms, especially during summer at higher latitudes where photoperiods are long.

  7. pH gradients in the diffusive boundary layer of subarctic macrophytes

    KAUST Repository

    Hendriks, Iris E.

    2017-06-20

    Highly productive macrophytes produce diurnal and seasonal cycles in CO concentrations modulated by metabolic activity, which cause discrepancies between pH in the bulk water and near seaweed blades, especially when entering the diffusion boundary layer (DBL). Calcifying epiphytic organisms living in this environment are therefore exposed to a different pH environment than that of the water column. To evaluate the actual pH environment on blade surfaces, we measured the thickness of the DBL and pH gradients within it for six subarctic macrophytes: Fucus vesiculosus, Ascophyllum nodosum, Ulva lactuca, Zostera marina, Saccharina longicruris, and Agarum clathratum. We measured pH under laboratory conditions at ambient temperatures (2–3 °C) and slow, stable flow over the blade surface at five light intensities (dark, 30, 50, 100 and 200 µmol photons m s). Boundary layer thickness ranged between 511 a