proton pump mechanism: Topics by WorldWideScience.org

Sample records for proton pump mechanism

Proton Pumps: Mechanism of Action and Applications

Science.gov (United States)

Lanyi, Janos K.; Pohorille, Andrew; DeVincenzi, Donald L. (Technical Monitor)

2001-01-01

Recent progress in understanding molecular structures and mechanisms of action of proton pumps has paved the way to their novel applications in biotechnology. Proton pumps, in particular bacteriorhodopsin and ATP synthases, are capable of continuous, renewable conversion of light to chemical, mechanical or electrical energy, which can be used in macro- or nano-scale devices. The capability of protein systems incorporated into liposomes to generate ATP, which can be further used to drive chemical reactions, and to act as molecular motors has been already demonstrated. Other possible applications of such biochemical devices include targeted drug delivery and biocatalytic re actors. All these devices might prove superior to their inorganic alternatives.
Conformational change during photocycle of bacteriorhodopsin and its proton-pumping mechanism.

Science.gov (United States)

Chou, K C

1993-06-01

Based on the recent finding on the structural difference of seven helix bundles in the all-trans and 13-cis bacteriorhodopsins, the distances among the key groups performing the function of proton translocation as well as their microenvironments have been investigated. Consequently, a pore-gated model was proposed for the light-driven proton-pumping mechanism of bacteriorhodopsin. According to this model, the five double-bounded polyene chain in retinal chromophore can be phenomenologically likened to a molecular "lever," whose one end links to a "piston" (the beta-ionone ring) and the other end to a pump "relay station" (the Schiff base). During the photocycle of bacteriorhodopsin, the molecular "lever" is moving up and down as marked by the position change of the "piston," so as to trigger the gate of pore to open and close alternately. When the "piston" is up, the pore-controlled gate is open so that the water channel from Asp-96 to the Schiff base and that from the Schiff base to Asp-85 is established; when the "piston" is down, the pore-controlled gate is closed and the water channels for proton transportation in both the cytoplasmic half and extracellular half are blocked. The current model allows a consistent interpretation of a great deal of experimental data and also provides a useful basis for further investigating the mechanism of proton pumping by bacteriorhodopsin.
Proton pump inhibitor-induced tumour cell death by inhibition of a detoxification mechanism.

Science.gov (United States)

Fais, S

2010-05-01

This review presents a possible new approach against cancer, as represented by inhibition of proton pumps, a mechanism used by tumour cells to avoid intracellular accumulation of toxic substances. Proton pump inhibitors (PPIs) belong to a family of pro-drugs that are currently used in the treatment of peptic diseases needing acidity to be activated. PPIs target the acidic tumour mass, where they are metabolized, thus blocking proton traffic. Proton pump inhibition triggers a rapid cell death as a result of intracellular acidification, caspase activation and early accumulation of reactive oxygen species into tumour cells. As a whole, the devastating effect of PPIs on tumour cells suggest the triggering of a fatal cell toxification. Many human tumours, including melanoma, osteosarcoma, lymphomas and various adenocarcinomas are responsive to PPIs. This appears highly conceivable, in as much as almost all human tumours are acidic and express high levels of proton pumps. Paradoxically, metastatic tumours appear to be more responsive to PPIs being more acidic than the majority of primary tumours. However, two clinical trials test the effectiveness of PPIs in chemosensitizing melanoma and osteosarcoma patients. Indeed, tumour acidity represents a very potent mechanism of chemoresistance. A majority of cytotoxic agents, being weak bases, are quickly protonated outside and do not enter the cells, thus preventing drugs to reach specific cellular targets. Clinical data will provide the proof of concept on the use of PPIs as a new class of antitumour agent with a very low level of systemic toxicity as compared with standard chemotherapeutic agents.
A quantum chemical study of the mechanism for proton-coupled electron transfer leading to proton pumping in cytochrome c oxidase

Science.gov (United States)

Blomberg, Margareta R. A.; Siegbahn, Per E. M.

2010-10-01

The proton pumping mechanism in cytochrome c oxidase, the terminal enzyme in the respiratory chain, has been investigated using hybrid DFT with large chemical models. In previous studies, a gating mechanism was suggested based on electrostatic interpretations of kinetic experiments. The predictions from that analysis are tested here. The main result is that the suggestion of a positively charged transition state for proton transfer is confirmed, while some other suggestions for the gating are not supported. It is shown that a few critical relative energy values from the earlier studies are reproduced with quite high accuracy using the present model calculations. Examples are the forward barrier for proton transfer from the N-side of the membrane to the pump-loading site when the heme a cofactor is reduced, and the corresponding back leakage barrier when heme a is oxidised. An interesting new finding is an unexpected double-well potential for proton transfer from the N-side to the pump-loading site. In the intermediate between the two transition states found, the proton is bound to PropD on heme a. A possible purpose of this type of potential surface is suggested here. The accuracy of the present values are discussed in terms of their sensitivity to the choice of dielectric constant. Only one energy value, which is not critical for the present mechanism, varies significantly with this choice and is therefore less certain.
Protons and how they are transported by proton pumps

DEFF Research Database (Denmark)

Buch-Pedersen, Morten Jeppe; Pedersen, Bjørn Panyella; Nissen, Poul

2008-01-01

molecular components that allow the plasma membrane proton H(+)-ATPase to carry out proton transport against large membrane potentials. When divergent proton pumps such as the plasma membrane H(+)-ATPase, bacteriorhodopsin, and F(O)F(1) ATP synthase are compared, unifying mechanistic premises for biological...... proton pumps emerge. Most notably, the minimal pumping apparatus of all pumps consists of a central proton acceptor/donor, a positively charged residue to control pK (a) changes of the proton acceptor/donor, and bound water molecules to facilitate rapid proton transport along proton wires....
Sodium and Proton Effects on Inward Proton Transport through Na/K Pumps

Science.gov (United States)

Mitchell, Travis J.; Zugarramurdi, Camila; Olivera, J. Fernando; Gatto, Craig; Artigas, Pablo

2014-01-01

The Na/K pump hydrolyzes ATP to export three intracellular Na (Nai) as it imports two extracellular K (Ko) across animal plasma membranes. Within the protein, two ion-binding sites (sites I and II) can reciprocally bind Na or K, but a third site (site III) exclusively binds Na in a voltage-dependent fashion. In the absence of Nao and Ko, the pump passively imports protons, generating an inward current (IH). To elucidate the mechanisms of IH, we used voltage-clamp techniques to investigate the [H]o, [Na]o, and voltage dependence of IH in Na/K pumps from ventricular myocytes and in ouabain-resistant pumps expressed in Xenopus oocytes. Lowering pHo revealed that Ho both activates IH (in a voltage-dependent manner) and inhibits it (in a voltage-independent manner) by binding to different sites. Nao effects depend on pHo; at pHo where no Ho inhibition is observed, Nao inhibits IH at all concentrations, but when applied at pHo that inhibits pump-mediated current, low [Na]o activates IH and high [Na]o inhibits it. Our results demonstrate that IH is a property inherent to Na/K pumps, not linked to the oocyte expression environment, explains differences in the characteristics of IH previously reported in the literature, and supports a model in which 1), protons leak through site III; 2), binding of two Na or two protons to sites I and II inhibits proton transport; and 3), pumps with mixed Na/proton occupancy of sites I and II remain permeable to protons. PMID:24940773
Protons and how they are transported by proton pumps

DEFF Research Database (Denmark)

Buch-Pedersen, Morten Jeppe; Pedersen, Bjørn Panyella; Veierskov, Bjarke

2008-01-01

The very high mobility of protons in aqueous solutions demands special features of membrane proton transporters to sustain efficient yet regulated proton transport across biological membranes. By the use of the chemical energy of ATP, plasma-membrane-embedded ATPases extrude protons from cells...... of plants and fungi to generate electrochemical proton gradients. The recently published crystal structure of a plasma membrane H(+)-ATPase contributes to our knowledge about the mechanism of these essential enzymes. Taking the biochemical and structural data together, we are now able to describe the basic...... molecular components that allow the plasma membrane proton H(+)-ATPase to carry out proton transport against large membrane potentials. When divergent proton pumps such as the plasma membrane H(+)-ATPase, bacteriorhodopsin, and F(O)F(1) ATP synthase are compared, unifying mechanistic premises for biological...
The safety of proton pump inhibitors in pregnancy

DEFF Research Database (Denmark)

Nielsen, Gunnar Lauge; Sørensen, Henrik Toft; Thulstrup, Ane Marie

1999-01-01

AIM: To assess the safety of proton pump inhibitors during pregnancy. METHODS: Fifty-one pregnant women exposed to proton pump inhibitors around the time of conception or during pregnancy were compared with 13 327 controls without exposure to any prescribed drug in a population-based study based...... birth weight or number of preterm deliveries in pregnancies exposed to proton pump inhibitors. However, further monitoring is warranted in order to establish or rule out a potential association between the use of proton pump inhibitors and increased risk of either cardiac malformations or preterm birth....
Piston-assisted proton pumping in Complex I of mitochondria membranes

Science.gov (United States)

Mourokh, Lev; Filonenko, Ilan

2014-03-01

Proton-pumping mechanism of Complex I remains mysterious because its electron and proton paths are well separated and the direct Coulomb interaction seems to be negligible. The structure of this enzyme was resolved very recently and its functionality was connected the shift of the helix HL. We model the helix as a piston oscillating between the protons and electrons. We assume that positive charges are accumulated near the edges of the helix. In the oxidized state, the piston is attracted to electrons, so its distance to the proton sites increases, the energy of these sites decreases and the sites can be populated. When electrons proceed to the drain, elastic forces return the piston to the original position and the energies of populated proton sites increase, so the protons can be transferred to the positive site of the membrane. In this work, we explore a simplified model when the interaction of the piston with electrons is replaced by a periodic force. We derive quantum Heisenberg equations for the proton operators and solve them jointly with the Langevin equation for the piston position. We show that the proton pumping is possible in such structure with parameters closely resembling the real system. We also address the feasibility of using such mechanism in nanoelectronics.
Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps.

Science.gov (United States)

Vedovato, Natascia; Gadsby, David C

2014-04-01

A single Na(+)/K(+)-ATPase pumps three Na(+) outwards and two K(+) inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na(+) than K(+) generates outward current across the cell membrane. Less well understood is the ability of Na(+)/K(+) pumps to generate an inward current of protons. Originally noted in pumps deprived of external K(+) and Na(+) ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K(+) and Na(+) concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na(+) release from phosphorylated Na(+)/K(+) pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na(+)/K(+) pumps that enables proton import is not required for completion of the 3 Na(+)/2 K(+) transport cycle. However, the back-step occurs readily during Na(+)/K(+) transport when external K(+) ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na(+)-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na(+) and K(+) ions that passes through binding site II. The inferred occurrence of Na(+)/K(+) exchange and H(+) import during the same conformational cycle of a single molecule identifies the Na(+)/K(+) pump as a hybrid transporter. Whether Na(+)/K(+) pump-mediated proton inflow may have any physiological or
Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps

Science.gov (United States)

Vedovato, Natascia

2014-01-01

A single Na+/K+-ATPase pumps three Na+ outwards and two K+ inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na+ than K+ generates outward current across the cell membrane. Less well understood is the ability of Na+/K+ pumps to generate an inward current of protons. Originally noted in pumps deprived of external K+ and Na+ ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K+ and Na+ concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na+ release from phosphorylated Na+/K+ pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na+/K+ pumps that enables proton import is not required for completion of the 3 Na+/2 K+ transport cycle. However, the back-step occurs readily during Na+/K+ transport when external K+ ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na+-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na+ and K+ ions that passes through binding site II. The inferred occurrence of Na+/K+ exchange and H+ import during the same conformational cycle of a single molecule identifies the Na+/K+ pump as a hybrid transporter. Whether Na+/K+ pump–mediated proton inflow may have any physiological or pathophysiological significance remains to be clarified. PMID
Proton pump inhibitors and osteoporosis

DEFF Research Database (Denmark)

Andersen, Bjarne Nesgaard; Johansen, Per Birger; Abrahamsen, Bo

2016-01-01

PURPOSE OF REVIEW: The purpose of the review is to provide an update on recent advances in the evidence based on proton pump inhibitors (PPI) as a possible cause of osteoporosis and osteoporotic fractures. This review focuses, in particular, on new studies published in the last 18 months and a di......PURPOSE OF REVIEW: The purpose of the review is to provide an update on recent advances in the evidence based on proton pump inhibitors (PPI) as a possible cause of osteoporosis and osteoporotic fractures. This review focuses, in particular, on new studies published in the last 18 months...... and a discussion of these findings and how this has influenced our understanding of this association, the clinical impact and the underlying pathophysiology. RECENT FINDINGS: New studies have further strengthened existing evidence linking use of PPIs to osteoporosis. Short-term use does not appear to pose a lower...... risk than long-term use. There is a continued lack of conclusive studies identifying the pathogenesis. Direct effects on calcium absorption or on osteoblast or osteoclast action cannot at present plausibly explain the mechanism. SUMMARY: The use of PPIs is a risk factor for development of osteoporosis...
Molecular mechanisms controlling proton pumping by bacteriorhodopsin. Final report

Energy Technology Data Exchange (ETDEWEB)

Crouch, Rosalie K.; Ebrey, Thomas G.

2000-02-10

Bacteriorhodopsin (bR) is the simplest biological system for the transduction of light energy. Light energy is directly converted to transmembrane proton gradient by a single, small membrane protein. The extraordinary stability of bR makes it an outstanding subject for bioenergetic studies. This project has focused on the role of interactions between key residues of the pigment involved in light-induced proton transfer. Methods to estimate the strength of these interactions and their correlation with the rate and efficiency of proton transfer have been developed. The concept of the coupling of the protonation states of key groups has been applied to individual steps of the proton transfer with the ultimate goal of understanding on the molecular level the driving forces for proton transport and the pathway of the transported proton in bT. The mechanism of light-induced proton release, uptake and the mechanism of recovery of initial state of bT has been examined. The experiments were performed with genetically engineered, site-specific mutants of bR. This has enabled us to characterize the role of individual amino acid residues in bR. Time resolved and low temperature absorption spectroscopy and light-induced photocurrent measurements were used in order to study the photochemical cycle and proton transfer in mutant pigments. Chemical modification and crosslinking of both the specific amino acids to the chromophore or to other amino acids were used to elucidate the role of light-induced conformational changes in the photocycle and the structure of the protein in the ground state. The results of this project provided new knowledge on the architecture of the proton transfer pathways inside the protein, on the mechanism of proton release in bR, and on the role of specific amino acid residues in the structure and function of bR.
RENAL SAFETY OF PROTON PUMP INHIBITORS

Directory of Open Access Journals (Sweden)

A. I. Dyadyk

2017-01-01

Full Text Available Proton pump inhibitors are a widely used in clinical practice, and are taken by millions of patients around the world for a long time. While proton pump inhibitors are well-tolerated class of drugs, the number of publications has been raised about adverse renal effects, specially their association with acute tubulointerstitial nephritis. It is one of the leading causes of acute renal injury and have catastrophic long-term consequences called chronic kidney disease. In this review, we consider epidemiology, pathogenesis, diagnostic criteria (including biopsy and morphological pattern, clinical manifestations and treatment of proton pump inhibitors-induced acute tubulointerstitial nephritis. A subclinical course without classical manifestations of a cell-mediated hypersensitivity reaction (fever, skin rash, eosinophilia, arthralgia is characteristic of acute tubulointerstitial nephritis. Increased serum creatinine, decreased glomerular filtration rate, electrolyte disorders, pathological changes in urine tests are not highly specific indicators, but allow to suspect the development of acute tubulointerstitial nephritis. The “gold” standard of diagnosis is the intravital morphological examination of the kidney tissue. Timely diagnosis and immediate discontinuation of the potentially causative drug is the mainstay of therapy and the first necessary step in the early management of suspected or biopsy-proven drug-induced acute tubulointerstitial nephritis. The usage of proton pump inhibitors should be performed only on strict indications with optimal duration of treatment and careful monitoring of kidney function. Multiple comorbidities (older age, heart failure, diabetes, cirrhosis, chronic kidney disease, hypovolemia increase potential nephrotoxicity. Awareness of this iatrogenic complication will improve diagnosis of proton pump inhibitors-induced acute tubulointerstitial nephritis by multidisciplinary specialists and increase the possibility
Crystal structure of the plasma membrane proton pump

DEFF Research Database (Denmark)

Pedersen, Bjørn P.; Buch-Pedersen, Morten Jeppe; Morth, J. Preben

2007-01-01

A prerequisite for life is the ability to maintain electrochemical imbalances across biomembranes. In all eukaryotes the plasma membrane potential and secondary transport systems are energized by the activity of P-type ATPase membrane proteins: H1-ATPase (the proton pump) in plants and fungi1......-3, and Na1,K1-ATPase (the sodium-potassium pump) in animals4. The name P-type derives from the fact that these proteins exploit a phosphorylated reaction cycle intermediate of ATP hydrolysis5.The plasma membrane proton pumps belong to the type III P-type ATPase subfamily, whereas Na1,K1-ATPase and Ca21......- ATPase are type II6. Electron microscopy has revealed the overall shape of proton pumps7, however, an atomic structure has been lacking. Here we present the first structure of a P-type proton pump determined by X-ray crystallography. Ten transmembrane helices and three cytoplasmic domains define...
Functional dissection of the proton pumping modules of mitochondrial complex I.

Directory of Open Access Journals (Sweden)

Stefan Dröse

2011-08-01

Full Text Available Mitochondrial complex I, the largest and most complicated proton pump of the respiratory chain, links the electron transfer from NADH to ubiquinone to the pumping of four protons from the matrix into the intermembrane space. In humans, defects in complex I are involved in a wide range of degenerative disorders. Recent progress in the X-ray structural analysis of prokaryotic and eukaryotic complex I confirmed that the redox reactions are confined entirely to the hydrophilic peripheral arm of the L-shaped molecule and take place at a remarkable distance from the membrane domain. While this clearly implies that the proton pumping within the membrane arm of complex I is driven indirectly via long-range conformational coupling, the molecular mechanism and the number, identity, and localization of the pump-sites remains unclear. Here, we report that upon deletion of the gene for a small accessory subunit of the Yarrowia complex I, a stable subcomplex (nb8mΔ is formed that lacks the distal part of the membrane domain as revealed by single particle analysis. The analysis of the subunit composition of holo and subcomplex by three complementary proteomic approaches revealed that two (ND4 and ND5 of the three subunits with homology to bacterial Mrp-type Na(+/H(+ antiporters that have been discussed as prime candidates for harbouring the proton pumps were missing in nb8mΔ. Nevertheless, nb8mΔ still pumps protons at half the stoichiometry of the complete enzyme. Our results provide evidence that the membrane arm of complex I harbours two functionally distinct pump modules that are connected in series by the long helical transmission element recently identified by X-ray structural analysis.
Crystallographic Structure of Xanthorhodopsin, the Light-Driven Proton Pump With a Dual Chromophore

International Nuclear Information System (INIS)

Luecke, H.; Schobert, B.; Stagno, J.; Imasheva, E.S.; Wang, J.M.; Balashov, S.P.; Lanyi, J.K

2008-01-01

Homologous to bacteriorhodopsin and even more to proteorhodopsin, xanthorhodopsin is a light-driven proton pump that, in addition to retinal, contains a noncovalently bound carotenoid with a function of a light-harvesting antenna. We determined the structure of this eubacterial membrane protein-carotenoid complex by X-ray diffraction, to 1.9-(angstrom) resolution. Although it contains 7 transmembrane helices like bacteriorhodopsin and archaerhodopsin, the structure of xanthorhodopsin is considerably different from the 2 archaeal proteins. The crystallographic model for this rhodopsin introduces structural motifs for proton transfer during the reaction cycle, particularly for proton release, that are dramatically different from those in other retinal-based transmembrane pumps. Further, it contains a histidine-aspartate complex for regulating the pK a of the primary proton acceptor not present in archaeal pumps but apparently conserved in eubacterial pumps. In addition to aiding elucidation of a more general proton transfer mechanism for light-driven energy transducers, the structure defines also the geometry of the carotenoid and the retinal. The close approach of the 2 polyenes at their ring ends explains why the efficiency of the excited-state energy transfer is as high as ∼45%, and the 46 o angle between them suggests that the chromophore location is a compromise between optimal capture of light of all polarization angles and excited-state energy transfer
Proton pump inhibitors inhibit pancreatic secretion

DEFF Research Database (Denmark)

Wang, Jing; Barbuskaite, Dagne; Tozzi, Marco

2015-01-01

+/K+-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar...... of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO3-, pancreas also secretes K+. In conclusion, this study calls for a revision of the basic model for HCO3- secretion. We propose that proton transport is driving secretion, and that in addition...
Proton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy.

Science.gov (United States)

Spugnini, Enrico P; Citro, Gennaro; Fais, Stefano

2010-05-08

The vacuolar ATPases are ATP-dependent proton pumps whose functions include the acidification of intracellular compartments and the extrusion of protons through the cell cytoplasmic membrane. These pumps play a pivotal role in the regulation of cell pH in normal cells and, to a much greater extent, in tumor cells. In fact, the glucose metabolism in hypoxic conditions by the neoplasms leads to an intercellular pH drift towards acidity. The acid microenvironment is modulated through the over-expression of H+ transporters that are also involved in tumor progression, invasiveness, distant spread and chemoresistance. Several strategies to block/downmodulate the efficiency of these transporters are currently being investigated. Among them, proton pump inhibitors have shown to successfully block the H+ transporters in vitro and in vivo, leading to apoptotic death. Furthermore, their action seems to synergize with conventional chemotherapy protocols, leading to chemosensitization and reversal of chemoresistance. Aim of this article is to critically revise the current knowledge of this cellular machinery and to summarize the therapeutic strategies developed to counter this mechanism.
Proton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy

Directory of Open Access Journals (Sweden)

Fais Stefano

2010-05-01

Full Text Available Abstract The vacuolar ATPases are ATP-dependent proton pumps whose functions include the acidification of intracellular compartments and the extrusion of protons through the cell cytoplasmic membrane. These pumps play a pivotal role in the regulation of cell pH in normal cells and, to a much greater extent, in tumor cells. In fact, the glucose metabolism in hypoxic conditions by the neoplasms leads to an intercellular pH drift towards acidity. The acid microenvironment is modulated through the over-expression of H+ transporters that are also involved in tumor progression, invasiveness, distant spread and chemoresistance. Several strategies to block/downmodulate the efficiency of these transporters are currently being investigated. Among them, proton pump inhibitors have shown to successfully block the H+ transporters in vitro and in vivo, leading to apoptotic death. Furthermore, their action seems to synergize with conventional chemotherapy protocols, leading to chemosensitization and reversal of chemoresistance. Aim of this article is to critically revise the current knowledge of this cellular machinery and to summarize the therapeutic strategies developed to counter this mechanism.

Collateral sensitivity between aminoglycosides and beta-lactam antibiotics depends on active proton pumps.

Science.gov (United States)

Azimi, Leila; Rastegar Lari, Abdolaziz

2017-11-01

Selection inversion is the hypothesis for antibiotic resistant inhabitation in bacteria and collateral sensitivity is one of the proposed phenomena for achievement of this hypothesis. The presence of collateral sensitivity associated with the proton motivation pump between the aminoglycosides and beta-lactam group of antibiotics is one of the examples of collateral sensitivity in some studies. The aim of this study was to demonstrate that collateral sensitivity between aminoglycosides and beta-lactam antibiotics associated with proton motivation pump may not be true in all cases. In this study, 100 Pseudomonas aeruginosa were surveyed. Gentamicin and imipenem-resistant strains were confirmed by disc diffusion method and MIC. Active proton motivation pumps were screened by pumps inhibitor. Semi-quantitative Real-Time PCR assay was used to confirm gene overexpression. Seventy-six and 79 out of 100 strains were resistant to gentamicin and imipenem, respectively. Seventy-five strains were resistant to both gentamicin and imipenem. The results of proton pump inhibitor test showed the involvement of active proton motivation pump in 22 of 75 imipenem- and gentamicin-resistant strains. According to Real - Time PCR assay, mexX efflux gene was overexpressed in the majority of isolates tested. The collateral sensitivity effect cannot explain the involvement of active proton motivation pumps in both imipenem and gentamicin-resistant strains simultaneously. Active and/or inactive proton pump in gentamicin-sensitive and/or resistant strains cannot be a suitable example for explanation of collateral sensitivity between aminoglycosides and beta-lactam antibiotics. Copyright © 2017 Elsevier Ltd. All rights reserved.
The purified ATPase from chromaffin granule membranes is an anion-dependent proton pump.

Science.gov (United States)

Moriyama, Y; Nelson, N

1987-07-05

The proton-ATPase of chromaffin granules was purified so as to maintain its proton-pumping activity when reconstituted into phospholipid vesicles. The purification procedure involved solubilization with polyoxyethylene 9 lauryl ether, hydroxylapatite column, precipitation by ammonium sulfate, and glycerol gradient centrifugation. The protease inhibitor mixture used in previous studies inhibited the proton-pumping activity of the enzyme; therefore, the protein was stabilized by pepstatin A and leupeptin. The enzyme was purified at least 50-fold with respect to both ATPase and proton-pumping activity. The ATP-dependent proton uptake activity of the reconstituted enzyme was absolutely dependent on the presence of Cl- or Br- outside the vesicles, whereas sulfate, acetate, formate, nitrate, and thiocyanate were inhibitory. Sulfate inhibition seems to be due to competition with Cl- on the anion-binding site outside the vesicles, whereas nitrate and thiocyanate inhibited only from the internal side. As with the inhibition by N-ethylmaleimide, the proton-pumping activity was much more sensitive to nitrate than the ATPase activity. About 20 mM nitrate were sufficient for 90% inhibition of the proton-pumping activity while 100 mM inhibited only 50% of the ATPase activity both in situ and in the reconstituted enzyme. The possible regulatory effect of anions on the ATP-dependent proton uptake in secretory granules is discussed.
Ionic Polymer Microactuator Activated by Photoresponsive Organic Proton Pumps

Directory of Open Access Journals (Sweden)

Khaled M. Al-Aribe

2015-10-01

Full Text Available An ionic polymer microactuator driven by an organic photoelectric proton pump transducer is described in this paper. The light responsive transducer is fabricated by using molecular self-assembly to immobilize oriented bacteriorhodopsin purple membrane (PM patches on a bio-functionalized porous anodic alumina (PAA substrate. When exposed to visible light, the PM proton pumps produce a unidirectional flow of ions through the structure’s nano-pores and alter the pH of the working solution in a microfluidic device. The change in pH is sufficient to generate an osmotic pressure difference across a hydroxyethyl methacrylate-acrylic acid (HEMA-AA actuator shell and induce volume expansion or contraction. Experiments show that the transducer can generate an ionic gradient of 2.5 μM and ionic potential of 25 mV, producing a pH increase of 0.42 in the working solution. The ΔpH is sufficient to increase the volume of the HEMA-AA microactuator by 80%. The volumetric transformation of the hydrogel can be used as a valve to close a fluid transport micro-channel or apply minute force to a mechanically flexible microcantilever beam.
[Pharmacogenic osteoporosis beyond cortisone. Proton pump inhibitors, glitazones and diuretics].

Science.gov (United States)

Kann, P H; Hadji, P; Bergmann, R S

2014-05-01

[corrected] There are many drugs which can cause osteoporosis or at least favor its initiation. The effect of hormones and drugs with antihormonal activity, such as glucocorticoids and aromatase inhibitors, on initiation of osteoporosis is well known. In addition, proton pump inhibitors, glitazones and diuretics also influence the formation of osteoporosis. The results of currently available studies on the correlation between proton pump inhibitors, glitazones and diuretics on formation of osteoporosis were evaluated and summarized. Proton pump inhibitors and glitazones increase the risk for osteoporotic fractures. Loop diuretics may slightly increase fracture risk, whereas thiazides were shown to be osteoprotective by reducing fracture probability on a relevant scale. Proton pump inhibitors should not be prescribed without serious consideration and then only as long as necessary. Alternatively, the administration of the less effective H2 antagonists should be considered when possible due to the reduction of acid secretion. Because the long-term intake of thiazides is associated with a clinically relevant reduction in the risk of fractures and they are economic and well-tolerated, prescription can be thoroughly recommended within the framework of differential diagnostic considerations in an appropriate clinical context. The briefly increased risk of falling immediately after starting diuretic therapy is the only point which needs to be considered.
Strategies for discontinuation of proton pump inhibitors

DEFF Research Database (Denmark)

Haastrup, Peter; Paulsen, Maja S; Begtrup, Luise M

2014-01-01

PURPOSE: Proton pump inhibitors (PPIs) are considered to be overprescribed. Consensus on how to attempt discontinuation is, however, lacking. We therefore conducted a systematic review of clinical studies on discontinuation of PPIs. METHODS: Systematic review based on clinical studies investigating...
High risk of drug-induced microscopic colitis with concomitant use of NSAIDs and proton pump inhibitors

NARCIS (Netherlands)

Verhaegh, B P M; de Vries, F; Masclee, A A M; Keshavarzian, A; de Boer, A; Souverein, P C; Pierik, M J; Jonkers, D M A E

2016-01-01

BACKGROUND: Microscopic colitis (MC) is a chronic bowel disorder characterised by watery diarrhoea. Nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs) and statins have been associated with MC. However, underlying mechanisms
Intrinsic uncoupling of mitochondrial proton pumps. 2. Modeling studies.

Science.gov (United States)

Pietrobon, D; Zoratti, M; Azzone, G F; Caplan, S R

1986-02-25

The thermodynamic and kinetic properties associated with intrinsic uncoupling in a six-state model of a redox proton pump have been studied by computing the flow-force relations for different degrees of coupling. Analysis of these relations shows the regulatory influence of the thermodynamic forces on the extent and relative contributions of redox slip and proton slip. Inhibition has been introduced into the model in two different ways, corresponding to possible modes of action of experimental inhibitors. Experiments relating the rate of electron transfer to delta microH at static head upon progressive inhibition of the pumps have been simulated considering (1) the limiting case that the nonzero rate of electron transfer at static head is only due to intrinsic uncoupling (no leaks) and (2) the experimentally observed case that about 30% of the nonzero rate of electron transfer at static head is due to a constant proton leakage conductance in parallel with the pumps, the rest being due to intrinsic uncoupling. The same simulations have been performed for experiments in which the rate of electron transfer is varied by varying the substrate concentration rather than by using an inhibitor. The corresponding experimental results obtained by measuring delta microH and the rate of electron transfer at different succinate concentrations in rat liver mitochondria are presented. Comparison between simulated behavior and experimental results leads to the general conclusion that the typical relationship between rate of electron transfer and delta microH found in mitochondria at static head could certainly be a manifestation of some degree of intrinsic uncoupling in the redox proton pumps.(ABSTRACT TRUNCATED AT 250 WORDS)
Proton pump inhibitors affect the gut microbiome

NARCIS (Netherlands)

Imhann, Floris; Bonder, Marc Jan; Vich Vila, Arnau; Fu, Jingyuan; Mujagic, Zlatan; Vork, Lisa; Feenstra, Ettje T.; Jankipersadsing, Soesma A; Cenit, Maria Carmen; Harmsen, Hermie J M; Dijkstra, Gerard; Franke, Lude; Xavier, Ramnik J; Jonkers, Daisy; Wijmenga, Cisca; Weersma, Rinse K; Zhernakova, Alexandra

BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or
A new hypothesis on the simultaneous direct and indirect proton pump mechanisms in NADH-quinone oxidoreductase (complex I).

Science.gov (United States)

Ohnishi, Tomoko; Nakamaru-Ogiso, Eiko; Ohnishi, S Tsuyoshi

2010-10-08

Recently, Sazanov's group reported the X-ray structure of whole complex I [Nature, 465, 441 (2010)], which presented a strong clue for a "piston-like" structure as a key element in an "indirect" proton pump. We have studied the NuoL subunit which has a high sequence similarity to Na(+)/H(+) antiporters, as do the NuoM and N subunits. We constructed 27 site-directed NuoL mutants. Our data suggest that the H(+)/e(-) stoichiometry seems to have decreased from (4H(+)/2e(-)) in the wild-type to approximately (3H(+)/2e(-)) in NuoL mutants. We propose a revised hypothesis that each of the "direct" and the "indirect" proton pumps transports 2H(+) per 2e(-). Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Exchangers man the pumps: Functional interplay between proton pumps and proton-coupled Ca exchangers.

Science.gov (United States)

Barkla, Bronwyn J; Hirschi, Kendal D; Pittman, Jon K

2008-05-01

Tonoplast-localised proton-coupled Ca(2+) transporters encoded by cation/H(+)exchanger (CAX) genes play a critical role in sequestering Ca(2+) into the vacuole. These transporters may function in coordination with Ca(2+) release channels, to shape stimulus-induced cytosolic Ca(2+) elevations. Recent analysis of Arabidopsis CAX knockout mutants, particularly cax1 and cax3, identified a variety of phenotypes including sensitivity to abiotic stresses, which indicated that these transporters might play a role in mediating the plant's stress response. A common feature of these mutants was the perturbation of H(+)-ATPase activity at both the tonoplast and the plasma membrane, suggesting a tight interplay between the Ca(2+)/H(+) exchangers and H(+) pumps. We speculate that indirect regulation of proton flux by the exchangers may be as important as the direct regulation of Ca(2+) flux. These results suggest cautious interpretation of mutant Ca(2+)/H(+) exchanger phenotypes that may be due to either perturbed Ca(2+) or H(+) transport.
Drug transport mechanism of the AcrB efflux pump.

Science.gov (United States)

Pos, Klaas M

2009-05-01

In Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, tripartite multidrug efflux systems extrude cytotoxic substances from the cell directly into the medium bypassing periplasm and the outer membrane. In E. coli, the tripartite efflux system AcrA/AcrB/TolC is the pump that extrudes multiple antibiotics, dyes, bile salts and detergents. The inner membrane component AcrB, a member of the Resistance Nodulation cell Division (RND) family, is the major site for substrate recognition and energy transduction of the entire tripartite system. The drug/proton antiport processes in this secondary transporter are suggested to be spatially separated, a feature frequently observed for primary transporters like membrane-bound ATPases. The recently elucidated asymmetric structure of the AcrB trimer reveals three different monomer conformations proposed to represent consecutive states in a directional transport cycle. Each monomer shows a distinct tunnel system with entrances located at the boundary of the outer leaflet of the inner membrane and the periplasm through the periplasmic porter (pore) domain towards the funnel of the trimer and TolC. In one monomer a hydrophobic pocket is present which has been shown to bind the AcrB substrates minocyclin and doxorubicin. The energy conversion from the proton motive force into drug efflux includes proton binding in (and release from) the transmembrane part. The conformational changes observed within a triad of essential, titratable residues (D407/D408/K940) residing in the hydrophobic transmembrane domain appear to be transduced by transmembrane helix 8 and associated with the conformational changes seen in the periplasmic domain. From the asymmetric structure a possible peristaltic pump transport mechanism based on a functional rotation of the AcrB trimer has been postulated. The novel drug transport model combines the alternate access pump mechanism with the rotating site catalysis of F(1)F(o) ATPase as
Shortcomings of the first-generation proton pump inhibitors

NARCIS (Netherlands)

Tytgat, G. N.

2001-01-01

Proton pump inhibitors (PPIs) are widely prescribed for the treatment of gastro-oesophageal reflux disease (GORD) as well as gastric and duodenal ulcers, and these agents are now considered the drugs of choice for managing such acid-related disorders. Despite their well-documented efficacy and
Optical silencing of C. elegans cells with light-driven proton pumps.

Science.gov (United States)

Okazaki, Ayako; Takahashi, Megumi; Toyoda, Naoya; Takagi, Shin

2014-08-01

Recent development of optogenetic techniques, which utilize light-driven ion channels or ion pumps for controlling the activity of excitable cells, has greatly facilitated the investigation of nervous systems in vivo. A new generation of optical silencers includes outward-directed proton pumps, such as Arch, which have several advantages over currently widely used halorhodopsin (NpHR). These advantages include the resistance to inactivation during prolonged illumination and the ability to generate a larger optical current from low intensity light. C. elegans, with its small transparent body and well-characterized neural circuits, is especially suitable for optogenetic analyses. In this article, we will outline the practical aspects of using of Arch and other proton pumps as optogenetic tools in C. elegans. Copyright © 2014 Elsevier Inc. All rights reserved.
MODULATION OF GROWTH AND PROTON PUMPING ATPase ACTIVITY OF PROBIOTIC Lactobacilli BY DIETARY CUCURBITS

Directory of Open Access Journals (Sweden)

Irfan Ahmad

2013-12-01

Full Text Available Gastrointestinal tract predominantly harbor probiotic Lactobacilli which exert beneficial effects on human health. Aqueous extracts from fruits of Lagenaria siceraria (Ls, Luffa cylindrica (Lc and Cucurbita maxima (Cm were prepared and lyophilized. Fruit extracts were investigated for their effects on Lactobacillus rhamnosus (L. rhamnosus, Lactobacillus plantarum (L. plantarum and Lactobacillus acidophilus (L. acidophilus. Extracts were found to enhance growth of Lactobacilli without any toxic effect (up to 1000µg/mL concentration. Minimum concentration of extracts at which growth of probiotic strains were found to be enhanced significantly were determined (103.67 µg/mL-118µg/mL and considered as effective concentration (EC or growth stimulatory concentration (GSC. Proton pumping ATPase activity of Lactobacilli were examined and found to be enhanced significantly (29.89- 61.96% in extracts treated probiotics (Lactobacilli as compared to the normal control. Inulin used as positive control and found to enhance the proton efflux activity (28.06-37.72% with respect to the control. These dietary cucurbits enhance metabolic activity of probiotic Lactobacilli by modulating their proton pumping ATPase mechanism. This study suggested that the consumption of cucurbit fruits might be a natural source of enhancing the activities of probiotic Lactobacilli in the gut.
Use of proton pump inhibitors after anti-reflux surgery

DEFF Research Database (Denmark)

Lodrup, A.; Pottegård, Anton; Hallas, J.

2014-01-01

Objective Antireflux surgery (ARS) has been suggested as an alternative to lifelong use of proton pump inhibitors (PPI) in reflux disease. Data from clinical trials on PPI use after ARS have been conflicting. We investigated PPI use after ARS in the general Danish population using nationwide...
Effects of membrane curvature and pH on proton pumping activity of single cytochrome bo3 enzymes

DEFF Research Database (Denmark)

Li, Mengqiu; Khan, Sanobar; Rong, Honglin

2017-01-01

The molecular mechanism of proton pumping by heme-copper oxidases (HCO) has intrigued the scientific community since it was first proposed. We have recently reported a novel technology that enables the continuous characterisation of proton transport activity of a HCO and ubiquinol oxidase from...... Escherichia coli, cytochrome bo3, for hundreds of seconds on the single enzyme level (Li et al. J Am Chem Soc 137 (2015) 16055–16063). Here, we have extended these studies by additional experiments and analyses of the proton transfer rate as a function of proteoliposome size and pH at the N- and P......-side of single HCOs. Proton transport activity of cytochrome bo3 was found to decrease with increased curvature of the membrane. Furthermore, proton uptake at the N-side (proton entrance) was insensitive to pH between pH 6.4–8.4, while proton release at the P-side had an optimum pH of ~ 7.4, suggesting...
[Proton pump inhibitors in gastro-oesophageal reflux disease: what is the further step?].

Science.gov (United States)

Simon, Mireille; Zerbib, Frank

2013-01-01

Optimisation of proton pump inhibitors use may improve reflux symptoms in 20-25% of the patients. Pathological gastro-oesophageal reflux should be documented in a patient with refractory reflux symptoms using upper endoscopy and/or pH testing. While on proton pump inhibitors twice daily, persistent symptoms are not related to gastro-oesophageal refluxdisease(GERD) in 50% of the patients. The new anti-reflux compounds have yet a limited efficacy and side effects that currently limit their development. Copyright © 2012. Published by Elsevier Masson SAS.
Effectiveness of ranitidine bismuth citrate and proton pump inhibitor ...

African Journals Online (AJOL)

Effectiveness of ranitidine bismuth citrate and proton pump inhibitor based triple therapies of Helicobacter pylori in Turkey. ... Results: When we look at the eradication rates of the treatment groups, only two groups (ranitidine bismuth citrate and rabeprazole groups) had eradication rates greater than 80%, both at intention to ...
Porphyromonas gingivalis is highly sensitive to inhibitors of a proton-pumping ATPase.

Science.gov (United States)

Sekiya, Mizuki; Shimoyama, Yu; Ishikawa, Taichi; Sasaki, Minoru; Futai, Masamitsu; Nakanishi-Matsui, Mayumi

2018-04-15

Porphyromonas gingivalis is a well-known Gram-negative bacterium that causes periodontal disease. The bacterium metabolizes amino acids and peptides to obtain energy. An ion gradient across its plasma membrane is thought to be essential for nutrient import. However, it is unclear whether an ion-pumping ATPase responsible for the gradient is required for bacterial growth. Here, we report the inhibitory effect of protonophores and inhibitors of a proton-pumping ATPase on the growth of P. gingivalis. Among the compounds examined, curcumin and citreoviridin appreciably reduced the bacterial growth. Furthermore, these compounds inhibited the ATPase activity in the bacterial membrane, where the A-type proton-pumping ATPase (A-ATPase) is located. This study suggests that curcumin and citreoviridin inhibit the bacterial growth by inhibiting the A-ATPase in the P. gingivalis membrane. Copyright © 2018 Elsevier Inc. All rights reserved.
1-Arylsulfonyl-2-(Pyridylmethylsulfinyl) Benzimidazoles as New Proton Pump Inhibitor Prodrugs

Science.gov (United States)

Shin, Jai Moo; Sachs, George; Cho, Young-moon; Garst, Michael

2010-01-01

New arylsulfonyl proton pump inhibitor (PPI) prodrug forms were synthesized. These prodrugs provided longer residence time of an effective PPI plasma concentration, resulting in better gastric acid inhibition. PMID:20032890

Proton Pump Inhibition Increases Rapid Eye Movement Sleep in the Rat

Directory of Open Access Journals (Sweden)

Munazah Fazal Qureshi

2014-01-01

Full Text Available Increased bodily CO2 concentration alters cellular pH as well as sleep. The proton pump, which plays an important role in the homeostatic regulation of cellular pH, therefore, may modulate sleep. We investigated the effects of the proton pump inhibitor “lansoprazole” on sleep-wakefulness. Male Wistar rats were surgically prepared for chronic polysomnographic recordings. Two different doses of lansoprazole (low: 1 mg/kg; high: 10 mg/kg were injected intraperitoneally in the same animal (n=7 and sleep-wakefulness was recorded for 6 hrs. The changes in sleep-wakefulness were compared statistically. Percent REM sleep amount in the vehicle and lansoprazole low dose groups was 9.26±1.03 and 9.09±0.54, respectively, which increased significantly in the lansoprazole high dose group by 31.75% (from vehicle and 34.21% (from low dose. Also, REM sleep episode numbers significantly increased in lansoprazole high dose group. Further, the sodium-hydrogen exchanger blocker “amiloride” (10 mg/kg; i.p. (n=5 did not alter sleep-wake architecture. Our results suggest that the proton pump plays an important role in REM sleep modulation and supports our view that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep.
Use of proton pump inhibitors and the risk of listeriosis

DEFF Research Database (Denmark)

Jensen, Anne Kvistholm; Simonsen, Jacob; Ethelberg, Steen

2017-01-01

BACKGROUND: Recent studies suggest that proton pump inhibitors (PPIs) may increase the risk for listeriosis. We aimed to investigate a potential association in cases of non-pregnancy associated listeriosis, using registry data. METHODS: We conducted a population-based case-control study using...
Structure of a Prokaryotic Virtual Proton Pump at 3.2 Astroms Resolution

Energy Technology Data Exchange (ETDEWEB)

Fang, Y.; Jayaram, H; Shane, T; Partensky, L; Wu, F; williams, C; Xiong, Y; Miller, C

2009-01-01

To reach the mammalian gut, enteric bacteria must pass through the stomach. Many such organisms survive exposure to the harsh gastric environment (pH 1.5-4) by mounting extreme acid-resistance responses, one of which, the arginine-dependent system of Escherichia coli, has been studied at levels of cellular physiology, molecular genetics and protein biochemistry. This multiprotein system keeps the cytoplasm above pH 5 during acid challenge by continually pumping protons out of the cell using the free energy of arginine decarboxylation. At the heart of the process is a 'virtual proton pump' in the inner membrane, called AdiC, that imports L-arginine from the gastric juice and exports its decarboxylation product agmatine. AdiC belongs to the APC superfamily of membrane proteins, which transports amino acids, polyamines and organic cations in a multitude of biological roles, including delivery of arginine for nitric oxide synthesis, facilitation of insulin release from pancreatic beta-cells, and, when inappropriately overexpressed, provisioning of certain fast-growing neoplastic cells with amino acids. High-resolution structures and detailed transport mechanisms of APC transporters are currently unknown. Here we describe a crystal structure of AdiC at 3.2 A resolution. The protein is captured in an outward-open, substrate-free conformation with transmembrane architecture remarkably similar to that seen in four other families of apparently unrelated transport proteins.
Structure of a prokaryotic virtual proton pump at 3.2 Å resolution

Energy Technology Data Exchange (ETDEWEB)

Fang, Yiling; Jayaram, Hariharan; Shane, Tania; Kolmakova-Partensky, Ludmila; Wu, Fang; Williams, Carole; Xiong, Yong; Miller, Christopher; (Yale); (Brandeis)

2009-09-15

To reach the mammalian gut, enteric bacteria must pass through the stomach. Many such organisms survive exposure to the harsh gastric environment (pH 1.5-4) by mounting extreme acid-resistance responses, one of which, the arginine-dependent system of Escherichia coli, has been studied at levels of cellular physiology, molecular genetics and protein biochemistry. This multiprotein system keeps the cytoplasm above pH 5 during acid challenge by continually pumping protons out of the cell using the free energy of arginine decarboxylation. At the heart of the process is a 'virtual proton pump' in the inner membrane, called AdiC, that imports L-arginine from the gastric juice and exports its decarboxylation product agmatine. AdiC belongs to the APC superfamily of membrane proteins, which transports amino acids, polyamines and organic cations in a multitude of biological roles, including delivery of arginine for nitric oxide synthesis, facilitation of insulin release from pancreatic {beta}-cells, and, when inappropriately overexpressed, provisioning of certain fast-growing neoplastic cells with amino acids. High-resolution structures and detailed transport mechanisms of APC transporters are currently unknown. Here we describe a crystal structure of AdiC at 3.2 {angstrom} resolution. The protein is captured in an outward-open, substrate-free conformation with transmembrane architecture remarkably similar to that seen in four other families of apparently unrelated transport proteins.
The selectivity of the Na(+)/K(+)-pump is controlled by binding site protonation and self-correcting occlusion.

Science.gov (United States)

Rui, Huan; Artigas, Pablo; Roux, Benoît

2016-08-04

The Na(+)/K(+)-pump maintains the physiological K(+) and Na(+) electrochemical gradients across the cell membrane. It operates via an 'alternating-access' mechanism, making iterative transitions between inward-facing (E1) and outward-facing (E2) conformations. Although the general features of the transport cycle are known, the detailed physicochemical factors governing the binding site selectivity remain mysterious. Free energy molecular dynamics simulations show that the ion binding sites switch their binding specificity in E1 and E2. This is accompanied by small structural arrangements and changes in protonation states of the coordinating residues. Additional computations on structural models of the intermediate states along the conformational transition pathway reveal that the free energy barrier toward the occlusion step is considerably increased when the wrong type of ion is loaded into the binding pocket, prohibiting the pump cycle from proceeding forward. This self-correcting mechanism strengthens the overall transport selectivity and protects the stoichiometry of the pump cycle.
Proton pump inhibitors: potential cost reductions by applying prescribing guidelines.

LENUS (Irish Health Repository)

Cahir, Caitriona

2012-01-01

There are concerns that proton pump inhibitors (PPI) are being over prescribed in both primary and secondary care. This study aims to establish potential cost savings in a community drug scheme for a one year period according to published clinical and cost-effective guidelines for PPI prescribing.
Proton pump inhibitor-refractory gastroesophageal reflux disease: challenges and solutions

Science.gov (United States)

Mermelstein, Joseph; Chait Mermelstein, Alanna; Chait, Maxwell M

2018-01-01

A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist. PMID:29606884
Three cases of radiation esophagitis controlled with proton pump inhibitor

Energy Technology Data Exchange (ETDEWEB)

Murakami, Ryuji; Saito, Ryuichi; Miyazaki, Toshiyuki [Kumamoto Red Cross Hospital (Japan)

2002-04-01

Radiation esophagitis sometimes interrupts the radiation therapy due to swallowing pain and dysplasia. We experienced three cases of radiation-induced esophagitis controlled with proton pump inhibitor (PPI). These cases suggested etiologic relationship radiation esophagitis and gastroesophageal reflux disease (GERD). We should consider PPI as treatment option for radiation esophagitis. (author)
A rationale for the use of proton pump inhibitors as antineoplastic agents.

Science.gov (United States)

De Milito, Angelo; Marino, Maria Lucia; Fais, Stefano

2012-01-01

It is becoming increasingly acknowledged that tumorigenesis is not simply characterized by the accumulation of rapidly proliferating, genetically mutated cells. Microenvironmental biophysical factors like hypoxia and acidity dramatically condition cancer cells and act as selective forces for malignant cells, adapting through metabolic reprogramming towards aerobic glycolysis. Avoiding intracellular accumulation of lactic acid and protons, otherwise detrimental to cell survival is crucial for malignant cells to maintain cellular pH homeostasis. As a consequence of the upregulated expression and/or function of several pH-regulating systems, cancer cells display an alkaline intracellular pH (pHi) and an acidic extracellular pH (pHe). Among the pH-regulating proteins, proton pumps play an important role in both drug-resistance and metastatic spread, thus representing a suitable therapeutic target. Proton pump inhibitors (PPI) have been reported as cytotoxic drugs active against several human tumor cells and preclinical data have prompted the investigation of PPI as anticancer agents in humans. This review will update the current knowledge on the antitumor activities of PPI and their potential applications.
Proton Pumping and Slippage Dynamics of a Eukaryotic P-Type ATPase Studied at the Single-Molecule Level

DEFF Research Database (Denmark)

Veshaguri, Salome

In all eukaryotes the plasma membrane potential and secondary transport systems are energized by P-type ATPases whose regulation however remains poorly understood. Here we monitored at the single-molecule level the activity of the prototypic proton pumping P-type ATPase Arabidopsis thaliana isoform....... We propose that variable ATP/H+ stoichiometry emerges as a novel mechanism for adaptation when challenged with depletion of ATP that is likely relevant for other ATPases. Such measurements will provide indispensable insights into the mechanisms of function and regulation of many other ion...
Proton Pump Inhibitors and Risk of Rhabdomyolysis.

Science.gov (United States)

Duncan, Scott J; Howden, Colin W

2017-01-01

Proton pump inhibitors (PPIs) have been associated with a variety of adverse events, although the level of evidence for many of these is weak at best. Recently, one national regulatory authority has mandated a change to the labeling of one PPI based on reports of possible associated rhabdomyolysis. Thus, in this review we summarize the available evidence linking PPI use with rhabdomyolysis. The level of evidence is insufficient to establish a causal relationship and is largely based on sporadic case reports. In general, patients with suspected PPI-associated rhabdomyolysis have not been re-challenged with a PPI after recovery. The mechanism whereby PPIs might have been associated with rhabdomyolysis is unclear but possibly related to interaction with concomitantly administered drugs such as HMG-CoA reductase inhibitors (statins). For patients with rhabdomyolysis, a careful search must be made for possible etiological factors. In patients who recover from an episode of possible PPI-related rhabdomyolysis but do not have a genuine requirement for PPI treatment, the PPI should not be re-introduced. For those with a definite indication for ongoing PPI treatment, the PPI can be re-introduced but should preferably not be administered with a statin.
The selectivity of the Na+/K+-pump is controlled by binding site protonation and self-correcting occlusion

Science.gov (United States)

Rui, Huan; Artigas, Pablo; Roux, Benoît

2016-01-01

The Na+/K+-pump maintains the physiological K+ and Na+ electrochemical gradients across the cell membrane. It operates via an 'alternating-access' mechanism, making iterative transitions between inward-facing (E1) and outward-facing (E2) conformations. Although the general features of the transport cycle are known, the detailed physicochemical factors governing the binding site selectivity remain mysterious. Free energy molecular dynamics simulations show that the ion binding sites switch their binding specificity in E1 and E2. This is accompanied by small structural arrangements and changes in protonation states of the coordinating residues. Additional computations on structural models of the intermediate states along the conformational transition pathway reveal that the free energy barrier toward the occlusion step is considerably increased when the wrong type of ion is loaded into the binding pocket, prohibiting the pump cycle from proceeding forward. This self-correcting mechanism strengthens the overall transport selectivity and protects the stoichiometry of the pump cycle. DOI: http://dx.doi.org/10.7554/eLife.16616.001 PMID:27490484
Receptor kinase-mediated control of primary active proton pumping at the plasma membrane

DEFF Research Database (Denmark)

Fuglsang, Anja Thoe; Kristensen, Astrid; Cuin, Tracey A.

2014-01-01

Acidification of the cell wall space outside the plasma membrane is required for plant growth and is the result of proton extrusion by the plasma membrane-localized H+-ATPases. Here we show that the major plasma membrane proton pumps in Arabidopsis, AHA1 and AHA2, interact directly in vitro...... and in planta with PSY1R, a receptor kinase of the plasma membrane that serves as a receptor for the peptide growth hormone PSY1. The intracellular protein kinase domain of PSY1R phosphorylates AHA2/AHA1 at Thr-881, situated in the autoinhibitory region I of the C-terminal domain. When expressed in a yeast...... heterologous expression system, the introduction of a negative charge at this position caused pump activation. Application of PSY1 to plant seedlings induced rapid in planta phosphorylation at Thr-881, concomitant with an instantaneous increase in proton efflux from roots. The direct interaction between AHA2...
The acidity of the tumor microenvironment is a mechanism of immune escape that can be overcome by proton pump inhibitors

Science.gov (United States)

Bellone, Matteo; Calcinotto, Arianna; Filipazzi, Paola; De Milito, Angelo; Fais, Stefano; Rivoltini, Licia

2013-01-01

We have recently reported that lowering the pH to values that are frequently detected in tumors causes reversible anergy in both human and mouse CD8+ T lymphocytes in vitro. The same occurs in vivo, in the tumor microenvironment and the administration of proton pump inhibitors, which buffer tumor acidity, can revert T-cell anergy and increase the efficacy of immunotherapy. PMID:23483769
Bacterial infections in cirrhosis: Role of proton pump inhibitors and intestinal permeability

NARCIS (Netherlands)

L.G. van Vlerken (Lotte); E.J. Huisman (Ellen); B. van Hoek (Bart); W. Renooij (W.); F.W.M. de Rooij (Felix); P.D. Siersema (Peter); K.J. van Erpecum (Karel)

2012-01-01

textabstractBackground Cirrhotic patients are at considerable risk for bacterial infections, possibly through increased intestinal permeability and bacterial overgrowth. Proton pump inhibitors (PPIs) may increase infection risk. We aimed to explore the potential association between PPI use and
Should Helicobacter pylori be eradicated before starting long-term proton pump inhibitors?

NARCIS (Netherlands)

Rauws, E. A.

1997-01-01

Symptomatic gastro-oesophageal reflux disease is a common disorder characterized by pathological exposure of the distal oesophagus to acid. The management requires the control of symptoms, prevention of relapse and complications. Proton pump inhibitors are without doubt the most effective agents in
Towards structural and functional analysis of the plant plasma membrane proton pump

DEFF Research Database (Denmark)

Justesen, Bo Højen

The plasma membrane H+-ATPase is a proton pump essential for several physiological important processes in plants. Through the extrusion of protons from the cell, the PM H+-ATPase establishes and maintains a proton gradient used by proton coupled transporters and secondary active transport...... of nutrients and metabolites across the plasma membrane. Additional processes involving the PM H+-ATPase includes plant growth, development, and response to biotic and abiotic stresses. Extensive efforts have been made in attempts to elucidate the detailed physiological role and biochemical characteristics...... of plasma membrane H+-ATPases. Studies on the plasma membrane H+-ATPases have involved both in vivo and in vitro approaches, with the latter employing either solubilisation by detergent micelles, or reconstitution into lipid vesicles. Despite resulting in a large body of information on structure, function...
Nano-electro-mechanical pump: Giant pumping of water in carbon nanotubes

Science.gov (United States)

Farimani, Amir Barati; Heiranian, Mohammad; Aluru, Narayana R.

2016-05-01

A fully controllable nano-electro-mechanical device that can pump fluids at nanoscale is proposed. Using molecular dynamics simulations, we show that an applied electric field to an ion@C60 inside a water-filled carbon nanotube can pump water with excellent efficiency. The key physical mechanism governing the fluid pumping is the conversion of electrical energy into hydrodynamic flow with efficiencies as high as 64%. Our results show that water can be compressed up to 7% higher than its bulk value by applying electric fields. High flux of water (up to 13,000 molecules/ns) is obtained by the electro-mechanical, piston-cylinder-like moving mechanism of the ion@C60 in the CNT. This large flux results from the piston-like mechanism, compressibility of water (increase in density of water due to molecular ordering), orienting dipole along the electric field and efficient electrical to mechanical energy conversion. Our findings can pave the way towards efficient energy conversion, pumping of fluids at nanoscale, and drug delivery.
Development of a tritium monitor combined with an electrochemical tritium pump using a proton conducting oxide

Energy Technology Data Exchange (ETDEWEB)

Tanaka, M. [National Institute for Fusion Science, Toki, Gifu (Japan); Sugiyama, T. [Nagoya University, Fro-cho, Chikusa-ku, Nagoya (Japan)

2015-03-15

The detection of low level tritium is one of the key issues for tritium management in tritium handling facilities. Such a detection can be performed by tritium monitors based on proton conducting oxide technique. We tested a tritium monitoring system composed of a commercial proportional counter combined with an electrochemical hydrogen pump equipped with CaZr{sub 0.9}In{sub 0.1}O{sub 3-α} as proton conducting oxide. The hydrogen pump operated at 973 K under electrolysis conditions using tritiated water vapor (HTO). The proton conducting oxide extracts tritium molecules (HT) from HTO and tritium concentration is measured by the proportional counter. The advantage of the proposed tritium monitoring system is that it is able to convert HTO into molecular hydrogen.
Unraveling the Mechanism of a Reversible Photoactivated Molecular Proton Crane

NARCIS (Netherlands)

van der Loop, T.H.; Ruesink, F.; Amirjalayer, S.; Sanders, H. J.; Buma, W.J.; Woutersen, S.

2014-01-01

Structural dynamics of the photoactivated mol. proton crane 7-hydroxy-8-(morpholinomethyl)quinoline has been studied using femtosecond UV-pump IR-probe spectroscopy. Upon electronic excitation, a proton is transferred from the hydroxy to the amine group located on the rotatable morpholino side

Evidence-based support for the use of proton pump inhibitors in cancer therapy.

Science.gov (United States)

Fais, Stefano

2015-11-24

'We can only cure what we can understand first', said Otto H. Warburg, the 1931 Nobel laureate for his discovery on tumor metabolism. Unfortunately, we still don't know too much the mechanisms underlying of cancer development and progression. One of the unsolved mystery includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery, that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. One of the most mechanism to survive to the acidic tumor microenvironment are proton exchangers not allowing intracellular acidification through a continuous elimination of H(+) either outside the cells or within the internal vacuoles. This article wants to comment a translational process through which from the preclinical demonstration that a class of proton pump inhibitors (PPI) exploited worldwide for peptic ulcer treatment and gastroprotection are indeed chemosensitizers as well, we have got to the clinical proof of concept that PPI may well be included in new anti-cancer strategies, and with a solid background and rationale.
Functional and morphological changes of the mucous membrane of the stomach after long application of proton pump inhibitors

Directory of Open Access Journals (Sweden)

M. V. Markina

2010-04-01

Full Text Available Changes of mucous membrane of rats’ stomach after long term application of proton pump inhibition – Omeprazole. Increase of pepsin concentration, volume and рН in both fasting and basal gastric juice in comparison with the control was observed. It is established that the content of nitrates and nitrites in gastric juice and in the rats’ mixed saliva after the 12th day of introduction of proton pump inhibitors is 3:1.
Cost-effectiveness of histamine receptor-2 antagonist versus proton pump inhibitor for stress ulcer prophylaxis in critically ill patients*.

Science.gov (United States)

MacLaren, Robert; Campbell, Jon

2014-04-01

To examine the cost-effectiveness of using histamine receptor-2 antagonist or proton pump inhibitor for stress ulcer prophylaxis. Decision analysis model examining costs and effectiveness of using histamine receptor-2 antagonist or proton pump inhibitor for stress ulcer prophylaxis. Costs were expressed in 2012 U.S. dollars from the perspective of the institution and included drug regimens and the following outcomes: clinically significant stress-related mucosal bleed, ventilator-associated pneumonia, and Clostridium difficile infection. Effectiveness was the mortality risk associated with these outcomes and represented by survival. Costs, occurrence rates, and mortality probabilities were extracted from published data. A simulation model. A mixed adult ICU population. Histamine receptor-2 antagonist or proton pump inhibitor for 9 days of stress ulcer prophylaxis therapy. Output variables were expected costs, expected survival rates, incremental cost, and incremental survival rate. Univariate sensitivity analyses were conducted to determine the drivers of incremental cost and incremental survival. Probabilistic sensitivity analysis was conducted using second-order Monte Carlo simulation. For the base case analysis, the expected cost of providing stress ulcer prophylaxis was $6,707 with histamine receptor-2 antagonist and $7,802 with proton pump inhibitor, resulting in a cost saving of $1,095 with histamine receptor-2 antagonist. The associated mortality probabilities were 3.819% and 3.825%, respectively, resulting in an absolute survival benefit of 0.006% with histamine receptor-2 antagonist. The primary drivers of incremental cost and survival were the assumptions surrounding ventilator-associated pneumonia and bleed. The probabilities that histamine receptor-2 antagonist was less costly and provided favorable survival were 89.4% and 55.7%, respectively. A secondary analysis assuming equal rates of C. difficile infection showed a cost saving of $908 with histamine
Development of new design mechanical seal tester for Primary Loop Recirculation Pump (PLR Pump)

International Nuclear Information System (INIS)

Fukushima, Naoki; Koshiba, Koremutsu

1995-01-01

The mechanical seal for a Primary Loop Recirculation Pump (PLR Pump) is an important part of a BWR plant. This study describes a new mechanical seal tester developed to certify mechanical seal performance before installation in a PLR Pump on site. (author)
Occupational Airborne Contact Dermatitis From Proton Pump Inhibitors.

Science.gov (United States)

DeKoven, Joel G; Yu, Ashley M

2015-01-01

Few published reports have described occupational contact dermatitis from proton pump inhibitor (PPI) exposure in the literature. We present an additional case of a 58-year-old male pharmaceutical worker with an occupational airborne allergic contact dermatitis to PPIs confirmed by patch testing. This is a novel report of workplace exposure to dexlansoprazole and esomeprazole PPIs with resultant clinical contact allergy and relevant positive patch test results to these 2 agents. A literature review of all previously reported cases of occupational contact dermatitis to PPI is summarized. The case also emphasizes the importance of even minute exposures when considering workplace accommodation.
Proton-pumping rhodopsins are abundantly expressed by microbial eukaryotes in a high-Arctic fjord.

Science.gov (United States)

Vader, Anna; Laughinghouse, Haywood D; Griffiths, Colin; Jakobsen, Kjetill S; Gabrielsen, Tove M

2018-02-01

Proton-pumping rhodopsins provide an alternative pathway to photosynthesis by which solar energy can enter the marine food web. Rhodopsin genes are widely found in marine bacteria, also in the Arctic, and were recently reported from several eukaryotic lineages. So far, little is known about rhodopsin expression in Arctic eukaryotes. In this study, we used metatranscriptomics and 18S rDNA tag sequencing to examine the mid-summer function and composition of marine protists (size 0.45-10 µm) in the high-Arctic Billefjorden (Spitsbergen), especially focussing on the expression of microbial proton-pumping rhodopsins. Rhodopsin transcripts were highly abundant, at a level similar to that of genes involved in photosynthesis. Phylogenetic analyses placed the environmental rhodopsins within disparate eukaryotic lineages, including dinoflagellates, stramenopiles, haptophytes and cryptophytes. Sequence comparison indicated the presence of several functional types, including xanthorhodopsins and a eukaryotic clade of proteorhodopsin. Transcripts belonging to the proteorhodopsin clade were also abundant in published metatranscriptomes from other oceanic regions, suggesting a global distribution. The diversity and abundance of rhodopsins show that these light-driven proton pumps play an important role in Arctic microbial eukaryotes. Understanding this role is imperative to predicting the future of the Arctic marine ecosystem faced by a changing light climate due to diminishing sea-ice. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.
Mechanical pumping at low temperature

International Nuclear Information System (INIS)

Perin, J.P.; Claudet, G.; Disdier, F.

1995-01-01

This novel concept consist of a mechanical pump able to run at low temperature (25K). Since gas density varies inversely with temperature, this pump would deliver much higher mass flow rate than at room temperature for a given size. Advantages of this concept are order of magnitude reduction in size, weight, when compared to a conventional pump scaled to perform the same mass flow rate at room temperature. This pump would be a solution to allow continuously tritium extraction and minimize the mass inventory. (orig.)
Mechanical vaccum pumps

CERN Document Server

Chew, A D

2007-01-01

This presentation gives an overview of the technology of contemporary primary and secondary mechanical vacuum pumps. For reference a brief history of vacuum and a summary of important and basic vacuum concepts are first presented.
Pharmacokinetics and pharmacodynamics of the proton pump inhibitors.

Science.gov (United States)

Shin, Jai Moo; Kim, Nayoung

2013-01-01

Proton pump inhibitor (PPI) is a prodrug which is activated by acid. Activated PPI binds covalently to the gastric H(+), K(+)-ATPase via disulfide bond. Cys813 is the primary site responsible for the inhibition of acid pump enzyme, where PPIs bind. Omeprazole was the first PPI introduced in market, followed by pantoprazole, lansoprazole and rabeprazole. Though these PPIs share the core structures benzimidazole and pyridine, their pharmacokinetics and pharmacodynamics are a little different. Several factors must be considered in understanding the pharmacodynamics of PPIs, including: accumulation of PPI in the parietal cell, the proportion of the pump enzyme located at the canaliculus, de novo synthesis of new pump enzyme, metabolism of PPI, amounts of covalent binding of PPI in the parietal cell, and the stability of PPI binding. PPIs have about 1hour of elimination half-life. Area under the plasmic concentration curve and the intragastric pH profile are very good indicators for evaluating PPI efficacy. Though CYP2C19 and CYP3A4 polymorphism are major components of PPI metabolism, the pharmacokinetics and pharmacodynamics of racemic mixture of PPIs depend on the CYP2C19 genotype status. S-omeprazole is relatively insensitive to CYP2C19, so better control of the intragastric pH is achieved. Similarly, R-lansoprazole was developed in order to increase the drug activity. Delayed-release formulation resulted in a longer duration of effective concentration of R-lansoprazole in blood, in addition to metabolic advantage. Thus, dexlansoprazole showed best control of the intragastric pH among the present PPIs. Overall, PPIs made significant progress in the management of acid-related diseases and improved health-related quality of life.
Mechanical pumping at low temperature

Energy Technology Data Exchange (ETDEWEB)

Perin, J.P.; Claudet, G.; Disdier, F.

1994-12-31

This new concept consists of a mechanical pump able to run at low temperature (25 K). Since gas density varies inversely with temperature, the pump could deliver much higher mass flow rate than at room temperature for a given size. Advantages of this concept are reduction of an order of magnitude in size and weight when compared to a conventional pump scaled to perform the same mass flow rate at room temperature. Results obtained at 80 K and 25 K with a Holweck type molecular drag pump of 100 mm diameter and with few stages of a turbomolecular pump running at the same temperatures, are given. This pump would be a solution to allow continuous tritium extraction and minimize the mass inventory for the ITER (International Tokamak Experiment Reactor). 5 figs., 2 tabs., 4 refs.
Energizing porters by proton-motive force.

Science.gov (United States)

Nelson, N

1994-11-01

It is generally accepted that the chemistry of water was the most crucial determinant in shaping life on earth. Among the more important chemical features of water is its dissociation into protons and hydroxyl ions. The presence of relatively high proton concentrations in the ambient solution resulted in the evolution of proton pumps during the dawn of life on earth. These proton pumps maintained neutral pH inside the cells and generated electrochemical gradients of protons (proton-motive force) across their membranes. The existence of proton-motive force enabled the evolution of porters driven by it that are most probably among the more primitive porters in the world. The directionality of the substrate transport by the porters could be to both sides of the membranes because they can serve as proton symporters or antiporters. One of the most important subjects of this meeting is the mechanism by which proton-motive and other ion-motive forces drive the transport processes through porters. Is there a common mechanism of action for all proton-driven porters? Is there some common partial reaction by which we can identify the way that porters are energized by proton-motive force? Is there a common coupling between proton movement and uptake or secretion of certain molecules? Even a partial answer to one of these questions would advance our knowledge... or confusion. As my mentor Efraim Racker used to say: 'If you are not totally confused you do not understand the issue'.
Modulation of proton pumping across proteoliposome membranes reconstituted with tonoplast H(+)-ATPase from cultured rice (Oryza sativa L. var. Boro) cells by acyl steryl glucoside and steryl glucoside.

Science.gov (United States)

Yamaguchi, Mineo; Kasamo, Kunihiro

2002-07-01

Tonoplast H(+)-ATPase purified from cultured rice cells (Oryza sativa L. var. Boro) was reconstituted into asolectin liposomes containing steryl glucoside (SG) or acyl steryl glucoside (ASG), and the effects of SG and ASG on proton pumping, ATP-hydrolysis activity and proton permeability of the proteoliposome membranes were investigated. In the proteoliposomes containing 10 mol% SG, proton pumping and ATP-hydrolysis activity were increased to around 140% of those in SG-free proteoliposomes. In the proteoliposomes containing ASG, proton pumping and ATP-hydrolysis activity were decreased to one-tenth of those in ASG-free proteoliposomes at 15 mol% ASG; however, activity increased again slightly in the range between 20 and 40 mol% ASG. The change in proton pumping across the proteoliposome membrane is not due to a change of proteoliposome size nor to the location of the catalytic site of the tonoplast H(+)-ATPase in the proteoliposomes. SG and ASG also reduced the passive proton permeability of the proteoliposomes. These results show that SG and ASG modulate proton pumping across the tonoplast toward stimulation and depression, respectively, and they reduce the passive proton permeability of the tonoplast.
Association Between Proton Pump Inhibitor Use and Spontaneous Bacterial Peritonitis in Cirrhotic Patients with Ascites

Directory of Open Access Journals (Sweden)

Mélissa Ratelle

2014-01-01

Full Text Available BACKGROUND: There are data suggesting a link between proton pump inhibitor (PPI use and the development of spontaneous bacterial peritonitis (SBP in cirrhotic patients with ascites; however, these data are controversial.
Partial symptom-response to proton pump inhibitors in patients with non-erosive reflux disease or reflux oesophagitis - a post hoc analysis of 5796 patients

DEFF Research Database (Denmark)

Bytzer, P; van Zanten, S Veldhuyzen; Mattsson, H

2012-01-01

Although most patients with gastro-oesophageal reflux disease (GERD) benefit from proton pump inhibitor (PPI) therapy, some experience only partial symptom relief.......Although most patients with gastro-oesophageal reflux disease (GERD) benefit from proton pump inhibitor (PPI) therapy, some experience only partial symptom relief....
Prolonged utilization of proton pump inhibitors in patients with ischemic and valvular heart disease is associated with surgical treatments, weight loss and aggravates anemia.

Science.gov (United States)

Boban, Marko; Zulj, Marinko; Persic, Viktor; Medved, Igor; Zekanovic, Drazen; Vcev, Aleksandar

2016-09-15

Proton pump inhibitors (PPIs) are among the commonest drugs used nowadays. The aim of our study was to analyze prolonged utilization of proton pump inhibitors in medical therapy of patients with ischemic and valvular heart disease. Secondly, profile of utilization was scrutinized to patient characteristics and type of cardiovascular treatments. The study included consecutive patients scheduled for cardiovascular rehabilitation 2-6months after index cardiovascular treatment. Two hundred ninety-four patients (n=294/604; 48.7%) have been using proton pump inhibitor in their therapy after index cardiovascular treatment. Cardiovascular treatments were powerfully connected with utilization of PPIs; surgery 5.77 (95%-confidence intervals [CI]: 4.05-8.22; pvalvular heart disease utilized proton pump inhibitor in prolonged courses. Prolonged courses of PPIs were connected with existence and worsening of red blood count indexes, older age, lesser weight of patients and underutilization of cardioprotective drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Regulatory assembly of the vacuolar proton pump VoV1-ATPase in yeast cells by FLIM-FRET

Science.gov (United States)

Ernst, Stefan; Batisse, Claire; Zarrabi, Nawid; Böttcher, Bettina; Börsch, Michael

2010-02-01

We investigate the reversible disassembly of VOV1-ATPase in life yeast cells by time resolved confocal FRET imaging. VOV1-ATPase in the vacuolar membrane pumps protons from the cytosol into the vacuole. VOV1-ATPase is a rotary biological nanomotor driven by ATP hydrolysis. The emerging proton gradient is used for secondary transport processes as well as for pH and Ca2+ homoeostasis in the cell. The activity of the VOV1-ATPase is regulated through assembly / disassembly processes. During starvation the two parts of VOV1-ATPase start to disassemble. This process is reversed after addition of glucose. The exact mechanisms are unknown. To follow the disassembly / reassembly in vivo we tagged two subunits C and E with different fluorescent proteins. Cellular distributions of C and E were monitored using a duty cycle-optimized alternating laser excitation scheme (DCO-ALEX) for time resolved confocal FRET-FLIM measurements.
Inward H+ pump xenorhodopsin: Mechanism and alternative optogenetic approach

Czech Academy of Sciences Publication Activity Database

Shevchenko, V.; Mager, T.; Kovalev, K.; Polovinkin, V.; Alekseev, A.; Juettner, J.; Chizhov, I.; Bamann, C.; Vavourakis, C.; Ghai, Rohit; Gushchin, I.; Borshchevskiy, V.; Rogachev, A.; Melnikov, I.; Popov, A.; Balandin, T.; Rodriguez-Valera, F.; Manstein, D. J.; Bueldt, G.; Bamberg, E.; Gordeliy, V.

2017-01-01

Roč. 3, č. 9 (2017), č. článku e1603187. ISSN 2375-2548 R&D Projects: GA ČR(CZ) GA17-04828S Institutional support: RVO:60077344 Keywords : sensory rhodopsin * membrane-proteins * purple membrane * proton pump Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology
Clinical Efficacy of Proton Pump Inhibitor versus Prompt Endoscopy for Management of People with Dyspepsia

DEFF Research Database (Denmark)

Kjeldsen, Hans Christian; Lauritzen, Torsten; Christensen, Bo

Title: Clinical Efficacy of Proton Pump Inhibitor versus Prompt Endoscopy for Management of People with Dyspepsia: A Randomized Clinical Trial in General Practice. Purpose: To compare the clinical efficacy of two strategies for management of dyspepsia in general practice in a RCT design....... Setting: June 2000 to August 2002, 41 GPs, Aarhus County, Denmark Methods: 368 people with dyspepsia (epigastric pain/discomfort, no alarm symptoms) were randomly assigned to treatment with omeprazol 40 mg/day for two weeks (PPI group, n:185) or endoscopy (endoscopy group, n:183). Due to migration......, dyspeptic contacts to GP or patients' satisfaction. Conclusions: Prompt endoscopy was superior to proton pump inhibitor concerning symptom improvement in management of dyspepsia in general practice when pain/discomfort was the primary symptom. There were no differences between the two strategies in respect...
The analysis of Drug - Related Problems in patients with gastroesophageal reflux disease treated with proton-pump inhibitors

Directory of Open Access Journals (Sweden)

Milutinović Jelena D.

2015-01-01

Full Text Available Introduction: Drug-related problems are frequent in almost all therapeutic areas. Aims: The aim of this paper was to detect drug - related problems in patients with gastroesophageal reflux and to analyze their possible association with the patient characteristics. Material and methods: The study was designed as descriptive, retrospective, crosssectional study aiming to determine the most common drug - related problems in patients with gastro-esophageal reflux disease treated with proton-pump inhibitors. The survey was conducted at the Department of Gastroenterology, Clinical Centre in Kragujevac. The study enrolled all patients treated from gastroesophageal reflux disease with proton pump inhibitors during the time period from 1.1.2014 until 1.1.2015. The study used descriptive statistics (percentage distribution, mean and standard deviation. The correlation between the number of adverse events and patient characteristics was also calculated. Results: The average age of the patients was 55.97±15.811 years, and 43 of the patients (60.6 % were male. The average hospitalization duration was 12.30±8.89 days. Based on the Pharmaceutical Care Network Europe classification, there were 182 Drug-Related Problems which was, on average, 2.56 problems per patient. Only 5 patients (7% did not report any problem while 11 patients (15.49% had over 10 possible drug-drug interactions. The most common problems which occurred were erroneous drug choice, inappropriate administration and possible interactions between medications. Conclusions: Based on the results of this study, one must pay attention to possible drug interactions and other problems which may occur with proton-pump inhibitors. Recognition of different sub-types of drug-related problems and of factors associated with drug related problems may reduce risk from adverse outcomes of gastro-esophageal reflux disease treatment with proton pump inhibitors.
Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan.

Science.gov (United States)

Mizuno, Hideki; Matsuhashi, Nobuyuki; Sakaguchi, Masahiro; Inoue, Syuji; Nakada, Koji; Higuchi, Kazuhide; Haruma, Ken; Joh, Takashi

2015-11-01

Proton pump inhibitors are the first-line treatment for reflux esophagitis. Because severe reflux esophagitis has very low prevalence in Japan, little is known about the effectiveness of proton pump inhibitors in these patients. This prospective multicenter study assessed the effectiveness of proton pump inhibitors for severe reflux esophagitis in Japan. Patients with modified Los Angeles grade C or D reflux esophagitis were treated with daily omeprazole (10 or 20 mg), lansoprazole (15 or 30 mg), or rabeprazole (10, 20, or 40 mg) for 8 weeks. Healing was assessed endoscopically, with questionnaires administered before and after treatment to measure the extent of reflux and dyspepsia symptoms. Factors affecting healing rates, including patient characteristics and endoscopic findings, were analyzed. Of the 115 patients enrolled, 64 with grade C and 19 with grade D reflux esophagitis completed the study. The healing rate was 67.5% (56/83), with 15 of the other 27 patients (55.6%) improving to grade A or B. No patient characteristic or endoscopic comorbidity was significantly associated with healing rate. Reflux and dyspepsia symptoms improved significantly with treatment. The low healing rate suggests the need of endoscopic examination to assess healing of reflux esophagitis at the end of therapy. (UMIN000005271).

Development of a hybrid chemical/mechanical heat pump

Science.gov (United States)

Grzyll, Lawrence R.; Silvestri, John J.; Scaringe, Robert P.

1991-01-01

The authors present the current development status of a hybrid chemical/mechanical heat pump for low-lift applications. The heat pump provides electronics cooling by evaporating a pure refrigerant from an absorbent/refrigerant mixture in a generator/cold plate. The current development focused on evaluation of absorbent/refrigerant pairs, corrosion testing, pump and compressor design, and electronic cold plate design. Two cycle configurations were considered. The first configuration utilized a standard mechanical compressor and pump. The second cycle configuration investigated pumps and compressors with non-moving parts. An innovative generator/cold plate design is also presented. The development to date shows that this cycle has about the same performance as standard vapor compression heat pumps with standard refrigerants but may have some performance and reliability advantages over vapor compression heat pumps.
Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species.

Science.gov (United States)

De Milito, Angelo; Iessi, Elisabetta; Logozzi, Mariantonia; Lozupone, Francesco; Spada, Massimo; Marino, Maria Lucia; Federici, Cristina; Perdicchio, Maurizio; Matarrese, Paola; Lugini, Luana; Nilsson, Anna; Fais, Stefano

2007-06-01

Proton pumps like the vacuolar-type H+ ATPase (V-ATPase) are involved in the control of cellular pH in normal and tumor cells. Treatment with proton pump inhibitors (PPI) induces sensitization of cancer cells to chemotherapeutics via modifications of cellular pH gradients. It is also known that low pH is the most suitable condition for a full PPI activation. Here, we tested whether PPI treatment in unbuffered culture conditions could affect survival and proliferation of human B-cell tumors. First, we showed that PPI treatment increased the sensitivity to vinblastine of a pre-B acute lymphoblastic leukemia (ALL) cell line. PPI, per se, induced a dose-dependent inhibition of proliferation of tumor B cells, which was associated with a dose- and time-dependent apoptotic-like cytotoxicity in B-cell lines and leukemic cells from patients with pre-B ALL. The effect of PPI was mediated by a very early production of reactive oxygen species (ROS), that preceded alkalinization of lysosomal pH, lysosomal membrane permeabilization, and cytosol acidification, suggesting an early destabilization of the acidic vesicular compartment. Lysosomal alterations were followed by mitochondrial membrane depolarization, release of cytochrome c, chromatin condensation, and caspase activation. However, inhibition of caspase activity did not affect PPI-induced cell death, whereas specific inhibition of ROS by an antioxidant (N-acetylcysteine) significantly delayed cell death and protected both lysosomal and mitochondrial membranes. The proapoptotic activity of PPI was consistent with a clear inhibition of tumor growth following PPI treatment of B-cell lymphoma in severe combined immunodeficient mice. This study further supports the importance of acidity and pH gradients in tumor cell homeostasis and suggests new therapeutic approaches for human B-cell tumors based on PPI.
Dietary Inulin Fibers Prevent Proton-Pump Inhibitor (PPI)-Induced Hypocalcemia in Mice.

Science.gov (United States)

Hess, Mark W; de Baaij, Jeroen H F; Gommers, Lisanne M M; Hoenderop, Joost G J; Bindels, René J M

2015-01-01

Proton-pump inhibitor-induced hypomagnesemia (PPIH) is the most recognized side effect of proton-pump inhibitors (PPIs). Additionally, PPIH is associated with hypocalcemia and hypokalemia. It is hypothesized that PPIs reduce epithelial proton secretion and thereby increase the pH in the colon, which may explain the reduced absorption of and Mg2+ and Ca2+. Fermentation of dietary oligofructose-enriched inulin fibers by the microflora leads to acidification of the intestinal lumen and by this enhances mineral uptake. This study aimed, therefore, to improve mineral absorption by application of dietary inulin to counteract PPIH. Here, C57BL/J6 mice were supplemented with omeprazole and/or inulin. Subsequently, Mg2+ and Ca2+ homeostasis was assessed by means of serum, urine and fecal electrolyte measurements. Moreover, the mRNA levels of magnesiotropic and calciotropic genes were examined in the large intestine and kidney by real-time PCR. Treatment with omeprazole significantly reduced serum Mg2+ and Ca2+ levels. However, concomitant addition of dietary inulin fibers normalized serum Ca2+ but not serum Mg2+ concentrations. Inulin abolished enhanced expression of Trpv6 and S100g in the colon by omeprazole. Additionally, intestinal and renal mRNA levels of the Trpm6 gene were reduced after inulin intake. This study suggests that dietary inulin counteracts reduced intestinal Ca2+ absorption upon PPI treatment. In contrast, inulin did not increase intestinal absorption of Mg2+ sufficiently to recover serum Mg2+. The clinical potential of dietary inulin treatment should be the subject of future studies.
Active glucose transport and proton pumping in tonoplast membrane of Zea mays L. coleoptiles are inhibited by anti-H+-ATPase antibodies

International Nuclear Information System (INIS)

Rausch, T.; Butcher, D.N.; Taiz, L.

1987-01-01

A tonoplast enriched fraction was obtained from Zea mays L. coleoptiles by isopycnic centrifugation of microsomal membranes in a sucrose step gradient. At the 18/26% interface chloride-stimulated and nitrate-inhibited proton pumping activity coincided with a Mg 2+ -ATP dependent accumulation of 3-O-methyl-D-glucose (OMG) as determined by a membrane filtration technique using 14 C-labeled substrate. OMG transport showed an apparently saturable component with a K/sub m/ of 110 micromolar, and was completely inhibited by 10 micromolar carbonyl cyanide m-chlorophenylhydrazone. Polyclonal antibodies against solubilized native tonoplast H + -ATPase and its 62 and 72 kilodalton subunits were assayed for their ability to inhibit proton pumping and OMG accumulation. Antibodies against both the native enzyme and the putative catalytic subunit strongly inhibited proton pumping and OMG transport whereas antibodies against the 62 kilodalton subunit had only a slight effect on both processes
Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease.

Science.gov (United States)

Cicala, Michele; Emerenziani, Sara; Guarino, Michele Pier Luca; Ribolsi, Mentore

2013-10-21

Gastro-esophageal reflux disease (GERD) is one of the most prevalent chronic diseases. Although proton pump inhibitors (PPIs) represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief, several studies have shown that up to 40% of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily. Several mechanisms have been proposed as involved in PPIs resistance, including ineffective control of gastric acid secretion, esophageal hypersensitivity, ultrastructural and functional changes in the esophageal epithelium. The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation, upper endoscopy, esophageal manometry and ambulatory pH-impedance monitoring, which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn. Treatment has been primarily based on doubling the PPI dose or switching to another PPI. Patients with proven disease, not responding to PPI twice daily, are eligible for anti-reflux surgery.
Restrained Proton Indicator in Combined Quantum-Mechanics/Molecular-Mechanics Dynamics Simulations of Proton Transfer through a Carbon Nanotube.

Science.gov (United States)

Duster, Adam W; Lin, Hai

2017-09-14

Recently, a collective variable "proton indicator" was purposed for tracking an excess proton solvated in bulk water in molecular dynamics simulations. In this work, we demonstrate the feasibility of utilizing the position of this proton indicator as a reaction coordinate to model an excess proton migrating through a hydrophobic carbon nanotube in combined quantum-mechanics/molecular-mechanics simulations. Our results indicate that applying a harmonic restraint to the proton indicator in the bulk solvent near the nanotube pore entrance leads to the recruitment of water molecules into the pore. This is consistent with an earlier study that employed a multistate empirical valence bond potential and a different representation (center of excess charge) of the proton. We attribute this water recruitment to the delocalized nature of the solvated proton, which prefers to be in high-dielectric bulk solvent. While water recruitment into the pore is considered an artifact in the present simulations (because of the artificially imposed restraint on the proton), if the proton were naturally restrained, it could assist in building water wires prior to proton transfer through the pore. The potential of mean force for a proton translocation through the water-filled pore was computed by umbrella sampling, where the bias potentials were applied to the proton indicator. The free energy curve and barrier heights agree reasonably with those in the literature. The results suggest that the proton indicator can be used as a reaction coordinate in simulations of proton transport in confined environments.
Limited ability of the proton-pump inhibitor test to identify patients with gastroesophageal reflux disease

DEFF Research Database (Denmark)

Bytzer, Peter; Jones, Roger; Vakil, Nimish

2012-01-01

The efficacy of proton-pump inhibitor (PPI) therapy often is assessed to determine whether patients' symptoms are acid-related and if patients have gastroesophageal reflux disease (GERD), although the accuracy of this approach is questionable. We evaluated the diagnostic performance of the PPI test...
The mechanism of electron gating in proton pumping cytochrome c oxidase: the effect of pH and temperature on internal electron transfer.

Science.gov (United States)

Brzezinski, P; Malmström, B G

1987-10-29

Electron-transfer reactions following flash photolysis of the mixed-valence cytochrome oxidase-CO complex have been measured at 445, 598 and 830 nm between pH 5.2 and 9.0 in the temperature range of 0-25 degrees C. There is a rapid electron transfer from the cytochrome a3-CuB pair to CuA (time constant: 14200 s-1), which is followed by a slower electron transfer to cytochrome a. Both the rate and the amplitude of the rapid phase are independent of pH, and the rate in the direction from CuA to cytochrome a3-CuB is practically independent of temperature. The second phase depends strongly on pH due to the titration of an acid-base group with pKa = 7.6. The equilibrium at pH 7.4 corresponds to reduction potentials of 225 and 345 mV for cytochrome a and a3, respectively, from which it is concluded that the enzyme is in a different conformation compared to the fully oxidized form. The results have been used to suggest a series of reaction steps in a cycle of the oxidase as a proton pump. Application of the electron-transfer theory to the temperature-dependence data suggests a mechanism for electron gating in the pump. Reduction of both cytochrome a and CuA leads to a conformational change, which changes the structure of cytochrome a3-CuB in such a way that the reorganizational barrier for electron transfer is removed and the driving force is increased.
Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach

NARCIS (Netherlands)

Rohof, Wout O.; Bennink, Roelof J.; Boeckxstaens, Guy E.

2014-01-01

The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease
Proton Pump for O-2 Reduction Catalyzed by 5,10,15,20-Tetraphenylporphyrinatocobalt(II)

Czech Academy of Sciences Publication Activity Database

Partovi-Nia, R.; Su, B.; Li, F.; Gros, C. P.; Barbe, J.-M.; Samec, Zdeněk; Girault, H. H.

2009-01-01

Roč. 15, č. 10 (2009), s. 2335-2340 ISSN 0947-6539 R&D Projects: GA MŠk OC 177; GA ČR(CZ) GA203/07/1257 Institutional research plan: CEZ:AV0Z40400503 Keywords : cobalt * ferrocenes * hydrogen peroxide * oxygen reduction * proton pump Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.382, year: 2009
Hypoalbuminemia is a predictor of mortality and rebleeding in peptic ulcer bleeding under proton pump inhibitor use.

Science.gov (United States)

Cheng, Hsiu-Chi; Yang, Er-Hsiang; Wu, Chung-Tai; Wang, Wen-Lun; Chen, Po-Jun; Lin, Meng-Ying; Sheu, Bor-Shyang

2018-04-01

Peptic ulcer bleeding remains a deadly disease, and a simple indicator of long-term outcomes is crucial. This study validated whether hypoalbuminemia and its related factors in patients with peptic ulcer bleeding can indicate long-term mortality and rebleeding under proton pump inhibitor use. The prospective cohort study enrolled 426 patients with peptic ulcer bleeding who had high risk stigmata at endoscopy and had received endoscopic hemostasis. They were divided into 79 patients in the hypoalbuminemia group (Hypo-AG, serum albumin ulcer size ≥1.0 cm independently (p peptic ulcer bleeding can be an alarm indicator of all-cause mortality and recurrent bleeding in a long-term follow-up situation under proton pump inhibitor use (NCT01591083). Copyright © 2017. Published by Elsevier B.V.
Proton pump inhibitor use and association with spontaneous bacterial peritonitis in patients with cirrhosis and ascites.

Science.gov (United States)

Siple, Jolene F; Morey, Jessica M; Gutman, Tracy E; Weinberg, Kathy L; Collins, Peggie D

2012-10-01

To evaluate the literature regarding the efficacy and safety of proton pump inhibitors (PPIs) when they are used in patients with cirrhosis and ascites. A literature search was conducted using MEDLINE (1966-May 2012) and Web of Science (1990-May 2012) with the terms proton pump inhibitor, antisecretory therapy, cirrhosis, ascites, spontaneous bacterial peritonitis, and Clostridium difficile. The search was restricted to articles published in English on the use of PPIs in humans. Reference citations from identified published articles were reviewed for relevant information. All articles in English identified from the data sources were evaluated for inclusion. One case series, 8 retrospective case-control trials, and 1 meta-analysis were identified. Cirrhosis may cause complications such as portal hypertension, esophageal varices, and ascites. Patients may be prescribed PPIs without clear indications or because of their propensity to develop upper gastrointestinal symptoms and bleeding. However, gastric acidity is a major nonspecific defense mechanism and there is insufficient evidence on the need for chronic acid suppression in patients with cirrhosis. It is postulated that the portal hypertensive environment in cirrhosis and the acid suppression from PPIs can increase the risk of spontaneous bacterial peritonitis and C. difficile infection in patients with cirrhosis with ascites. Several retrospective studies and 1 meta-analysis have confirmed this association. Patients with cirrhosis and ascites should be monitored carefully while on PPIs for a possible increased risk of infection from spontaneous bacterial peritonitis and C. difficile. Prospective randomized trials are needed to confirm this association. Clinicians should be aware of this lesser known adverse effect of PPIs.
Proton pump inhibitors and gastroenteritis

International Nuclear Information System (INIS)

Hassing, Robert-Jan; Verbon, Annelies; Visser, Herman de; Hofman, Albert; Stricker, Bruno H.

2016-01-01

An association between proton pump inhibitor (PPI) therapy and bacterial gastroenteritis has been suggested as well as contradicted. The aim of this study was to examine the association between the use of PPIs and occurrence of bacterial gastroenteritis in the prospective Rotterdam Study. The Rotterdam Study is a population-based cohort study among 14,926 subjects aged 45 years and older with up to 24 years of follow-up. Analyses were performed with a generalized estimating equations method in participants who handed-in a diagnostic stool sample. Furthermore, a nested case–control analysis was performed using the total cohort as a reference group. A bacterial microorganism was isolated in 125 samples, whereas 1174 samples were culture negative. In the generalized estimating equations analysis, we found that participants with a bacterial gastroenteritis were more likely than controls to be current users of PPIs (adjusted OR 1.94; 95 % CI 1.15–3.25). Different sensitivity analyses did not change this result. A considerably higher effect was observed (adjusted OR 6.14; 95 % CI 3.81–9.91), using the total cohort as a reference in a nested case–control analysis. Current PPI therapy is associated with an increased risk of bacterial gastroenteritis. However, by reducing the risk of selection and information bias in our study design, we demonstrated that the effect is lower than previously assumed.
A highly reliable cryogenic mixing pump with no mechanical moving parts

Science.gov (United States)

Chen, W.; Niblick, A. L.

2017-12-01

This paper presents the design and preliminary test results of a novel cryogenic mixing pump based on magnetocaloric effect. The mixing pump is developed to enable long-term cryogenic propellant storage in space by preventing thermal stratification of cryogens in storage tanks. The mixing pump uses an innovative thermodynamic process to generate fluid jets to promote fluid mixing, eliminating the need for mechanical pumps. Its innovative mechanism uses a solid magnetocaloric material to alternately vaporize and condense the cryogen in the pumping chamber, and thus control the volume of the fluid inside the pumping chamber to produce pumping action. The pump is capable of self-priming and can generate a high-pressure rise. This paper discusses operating mechanism and design consideration of the pump, introduces the configuration of a brassboard cryogenic pump, and presents the preliminary test results of the pump with liquid nitrogen.
Diagnostic value of the proton pump inhibitor test for gastro-oesophageal reflux disease in primary care

NARCIS (Netherlands)

Aanen, M. C.; Weusten, B. L. A. M.; Numans, M. E.; de Wit, N. J.; Baron, A.; Smout, A. J. P. M.

2006-01-01

AIM: To assess the diagnostic accuracy of the proton pump inhibitor test in a primary care population as well as its additional value over reflux history, using the symptom association probability outcome during 24-h oesophageal pH recording as reference test for gastro-oesophageal reflux disease.
Causes of, and Therapeutic Approaches for, Proton Pump Inhibitor-Resistant Gastroesophageal Reflux Disease in Asia

OpenAIRE

Kinoshita, Yoshikazu; Ishihara, Shunji

2008-01-01

Proton pump inhibitors (PPIs) are the most widely used drugs for treatment of gastroesophageal reflux disease. However, approximately 20% of patients with reflux esophagitis and 40% of those with nonerosive reflux diseases complain of troublesome symptoms, even during treatment with PPIs. In patients with reflux esophagitis, dose escalation and co-administration with a histamine ...
Increased prandial air swallowing and postprandial gas-liquid reflux among patients refractory to proton pump inhibitor therapy

NARCIS (Netherlands)

Bravi, Ivana; Woodland, Philip; Gill, Ravinder S.; Al-Zinaty, Mohannad; Bredenoord, Albert J.; Sifrim, Daniel

2013-01-01

Many patients with gastroesophageal reflux disease (GERD) have persistent reflux despite treatment with proton pump inhibitors (PPIs). Mixed gas-liquid reflux events are more likely to be perceived as symptomatic. We used esophageal impedance monitoring to investigate whether esophageal gas is
Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB.

Science.gov (United States)

Eicher, Thomas; Seeger, Markus A; Anselmi, Claudio; Zhou, Wenchang; Brandstätter, Lorenz; Verrey, François; Diederichs, Kay; Faraldo-Gómez, José D; Pos, Klaas M

2014-09-19

Membrane transporters of the RND superfamily confer multidrug resistance to pathogenic bacteria, and are essential for cholesterol metabolism and embryonic development in humans. We use high-resolution X-ray crystallography and computational methods to delineate the mechanism of the homotrimeric RND-type proton/drug antiporter AcrB, the active component of the major efflux system AcrAB-TolC in Escherichia coli, and one most complex and intriguing membrane transporters known to date. Analysis of wildtype AcrB and four functionally-inactive variants reveals an unprecedented mechanism that involves two remote alternating-access conformational cycles within each protomer, namely one for protons in the transmembrane region and another for drugs in the periplasmic domain, 50 Å apart. Each of these cycles entails two distinct types of collective motions of two structural repeats, coupled by flanking α-helices that project from the membrane. Moreover, we rationalize how the cross-talk among protomers across the trimerization interface might lead to a more kinetically efficient efflux system.
The appropriateness of a proton pump inhibitor prescription.

LENUS (Irish Health Repository)

Moran, N

2014-11-01

Proton pump inhibitors (PPIs) are one of the most commonly prescribed groups of drug in Ireland, at great expense to the Irish healthcare executive. This study aims to evaluate the appropriateness of PPI prescriptions on admission and discharge in a tertiary referral hospital. All non-elective admissions in the Emergency Department in one week were included in the study. 102 patients in total were included, with 36 (35.4%) treated with a PPI on admission. Of these, only 3 (8.3%) had a clear indication noted as per current NICE guidelines. 18 new in-hospital PPI prescriptions were documented. 11 (61%) of which were present on discharge prescriptions. Continuing PPI prescription on discharge into the community may be inappropriate, costly and potentially harmful. Brief interventions aimed at reducing inappropriate PPI prescriptions have been shown to be effective at reducing the cost and potential harm of unnecessary treatment.
Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach.

Science.gov (United States)

Taylor, Sophie; Spugnini, Enrico Pierluigi; Assaraf, Yehuda G; Azzarito, Tommaso; Rauch, Cyril; Fais, Stefano

2015-11-01

Despite the major progresses in biomedical research and the development of novel therapeutics and treatment strategies, cancer is still among the dominant causes of death worldwide. One of the crucial challenges in the clinical management of cancer is primary (intrinsic) and secondary (acquired) resistance to both conventional and targeted chemotherapeutics. Multiple mechanisms have been identifiedthat underlie intrinsic and acquired chemoresistance: these include impaired drug uptake, increased drug efflux, deletion of receptors, altered drug metabolism, quantitative and qualitative alterations in drug targets, increased DNA damage repair and various mechanisms of anti-apoptosis. The fast efflux of anticancer drugs mediated by multidrug efflux pumps and the partial or complete reversibility of chemoresistance combined with the absence of genetic mutations suggests a multifactorial process. However, a growing body of recent evidence suggests that chemoresistance is often triggered by the highly acidic microenvironment of tumors. The vast majority of drugs, including conventional chemotherapeutics and more recent biological agents, are weak bases that are quickly protonated and neutralized in acidic environments, such as the extracellular microenvironment and the acidic organelles of tumor cells. It is therefore essential to develop new strategies to overcome the entrapment and neutralization of weak base drugs. One such strategy is the use of proton pump inhibitors which can enhance tumor chemosensitivity by increasing the pH of the tumor microenvironment. Recent clinical trials in animals with spontaneous tumors have indicated that patient alkalization is capable of reversing acquired chemoresistance in a large percentage of tumors that are refractory to chemotherapy. Of particular interest was the benefit of alkalization for patients undergoing metronomic regimens which are becoming more widely used in veterinary medicine. Overall, these results provide

Randomized controlled trial of transoral incisionless fundoplication vs. proton pump inhibitors for treatment of gastroesophageal reflux disease

NARCIS (Netherlands)

Witteman, B.P.; Conchillo, J.M.; Rinsma, N.F.; Betzel, B; Peeters, A.; Koek, G.H.; Stassen, L.P.; Bouvy, N.D.

2015-01-01

OBJECTIVES: Transoral incisionless fundoplication (TIF) was developed in an attempt to create a minimally invasive endoscopic procedure that mimics antireflux surgery. The objective of this trial was to evaluate effectiveness of TIF compared with proton pump inhibition in a population consisting of
Optimization of the pumping ring in a mechanical seal with an integrated cooler for feed-water pumps

International Nuclear Information System (INIS)

Buchdahl, D.; Martin, R.; Gueret, G.; Blanc, M.

1994-07-01

To simplify maintenance, E.D.F. along with its collaborators undertook the study of mechanical seal with integrated cooler used in feed-water pumps in the nuclear power plants. The cooler, integrated to the pump acts as a thermal barrier as well as a cooler of the mechanical seal. The water circulation in the cooler is assumed by an integrated pumping ring in the rotary part of the mechanical seal, with a matching screw thread in the pumping case. This assembly of mechanical seal/integrated cooler is tested in a test loop at the EDF/DER Laboratory. All working conditions are similar to that at site. Tests with different configurations of the rotor/stator profiles are performed, i.e.; different lengths and types of threading. Hydraulic performances and the global thermal balance of this assembly are studied. Our basic aim during these tests is to optimize the hydraulic performance of the pumping ring so as to best cool the mechanical seal faces. The different results obtained and the conclusions drawn during these tests are presented. (authors). 7 figs., 3 refs
Persistent gastro-oesophageal reflux symptoms despite proton pump inhibitor therapy.

Science.gov (United States)

Ang, Daphne; How, Choon How; Ang, Tiing Leong

2016-10-01

About one-third of patients with suspected gastro-oesophageal reflux disease (GERD) do not respond symptomatically to proton pump inhibitors (PPIs). Many of these patients do not suffer from GERD, but may have underlying functional heartburn or atypical chest pain. Other causes of failure to respond to PPIs include inadequate acid suppression, non-acid reflux, oesophageal hypersensitivity, oesophageal dysmotility and psychological comorbidities. Functional oesophageal tests can exclude cardiac and structural causes, as well as help to confi rm or exclude GERD. The use of PPIs should only be continued in the presence of acid reflux or oesophageal hypersensitivity for acid reflux-related events that is proven on functional oesophageal tests. Copyright: © Singapore Medical Association.
Delirium in the geriatric unit: proton-pump inhibitors and other risk factors.

Science.gov (United States)

Otremba, Iwona; Wilczyński, Krzysztof; Szewieczek, Jan

2016-01-01

Delirium remains a major nosocomial complication of hospitalized elderly. Predictive models for delirium may be useful for identification of high-risk patients for implementation of preventive strategies. Evaluate specific factors for development of delirium in a geriatric ward setting. Prospective cross-sectional study comprised 675 consecutive patients aged 79.2±7.7 years (66% women and 34% men), admitted to the subacute geriatric ward of a multiprofile university hospital after exclusion of 113 patients treated with antipsychotic medication because of behavioral disorders before admission. Comprehensive geriatric assessments including a structured interview, physical examination, geriatric functional assessment, blood sampling, ECG, abdominal ultrasound, chest X-ray, Confusion Assessment Method for diagnosis of delirium, Delirium-O-Meter to assess delirium severity, Richmond Agitation-Sedation Scale to assess sedation or agitation, visual analog scale and Doloplus-2 scale to assess pain level were performed. Multivariate logistic regression analysis revealed five independent factors associated with development of delirium in geriatric inpatients: transfer between hospital wards (odds ratio [OR] =2.78; confidence interval [CI] =1.54-5.01; P=0.001), preexisting dementia (OR =2.29; CI =1.44-3.65; Pfall incidents (OR =1.76; CI =1.17-2.64; P=0.006), and use of proton-pump inhibitors (OR =1.67; CI =1.11-2.53; P=0.014). Transfer between hospital wards, preexisting dementia, previous delirium incidents, previous fall incidents, and use of proton-pump inhibitors are predictive of development of delirium in the geriatric inpatient setting.
The prophylactic use of a proton pump inhibitor before food and alcohol.

LENUS (Irish Health Repository)

O'Leary, C

2012-02-03

BACKGROUND: Patients report that the prophylactic consumption of a proton pump inhibitor minimizes gastrointestinal symptoms expected to be provoked by late-night food and alcohol consumption. The efficacy of this practice has not been studied formally. AIM: To perform a randomized, double-blind, placebo-controlled trial of a single dose of lansoprazole (30 mg) taken prior to a large meal and alcohol consumption. METHODS: Study subjects were recruited randomly from local primary care and hospital physicians. Each participant (n = 56; 37 male, 19 female; mean age, 38 years) completed questionnaires before and after the meal. Approximately 90 min prior to the provocative meal, participants were witnessed taking either placebo or 30 mg lansoprazole. Bar tokens were dispensed to permit the accurate quantification of alcohol consumption (mean, 15 units). RESULTS: Forty per cent of subjects reported significant reflux symptoms. For the entire group, there was no significant difference between lansoprazole and placebo. Post-prandial reflux was more frequent in those consuming > 15 units of alcohol (13\\/26, 50%) compared with those consuming < 15 units (7\\/30, 24%; P < 0.05). In the group who consumed > 15 units of alcohol, lansoprazole was associated with a lower rate of heartburn (5\\/15, 33%) compared with placebo (8\\/11, 73%; P < 0.05). CONCLUSION: A single dose of a proton pump inhibitor prior to indulgence was only associated with reduced heartburn in those consuming > 15 units of alcohol.
Proton pump inhibitors for the treatment of patients with erosive esophagitis and gastroesophageal reflux disease: current evidence and safety of dexlansoprazole

Directory of Open Access Journals (Sweden)

Mermelstein J

2016-07-01

Full Text Available Joseph Mermelstein,1 Alanna Chait Mermelstein,2 Maxwell M Chait,3 1Department of Medicine, Mount Sinai Beth Israel/Icahn School of Medicine, 2Department of Psychiatry, New York Presbyterian Hospital/Weill Cornell Medicine, 3Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA Abstract: Gastroesophageal reflux disease is the most common upper gastroenterology disorder in the US. It is associated with a variety of complications and significantly impacts quality of life. Proton pump inhibitors are the most effective treatment. Dexlansoprazole modified release (MR is a proton pump inhibitor that employs a novel release formulation that prolongs its absorption and allows for more flexibility in dosing. Dexlansoprazole MR can be dosed without regard to food intake or time of day, and once-daily dosing may replace twice-daily dosing of other agents. Dexlansoprazole MR is effective for healing and maintenance of erosive esophagitis, and for the treatment of nonerosive disease, including nocturnal gastroesophageal reflux disease. Dexlansoprazole MR is safe and well tolerated, and can improve quality of life. Keywords: dexlansoprazole, proton pump inhibitors, gastroesophageal reflux disease, erosive esophagitis
Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits.

Science.gov (United States)

Gwee, Kok Ann; Goh, Vernadine; Lima, Graca; Setia, Sajita

2018-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often coadministered with proton-pump inhibitors (PPIs) to reduce NSAID-induced gastrointestinal (GI) adverse events. This coadministration is generally regarded as safe, and is included in many of the guidelines on NSAID prescription. However, recent evidence indicates that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs. This review discusses the GI effects and complications of NSAIDs and how PPIs may potentiate these effects, options for prevention of GI side effects, and appropriate use of PPIs in combination with NSAIDs.
Plant proton pumps

DEFF Research Database (Denmark)

Gaxiola, Roberto A.; Palmgren, Michael Gjedde; Schumacher, Karin

2007-01-01

Chemiosmotic circuits of plant cells are driven by proton (H+) gradients that mediate secondary active transport of compounds across plasma and endosomal membranes. Furthermore, regulation of endosomal acidification is critical for endocytic and secretory pathways. For plants to react...
Clopidogrel and proton pump inhibitors--where do we stand in 2012?

LENUS (Irish Health Repository)

Drepper, Michael D

2012-05-14

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events. Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines. Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19 (CYP2C19) and proton pump inhibitors (PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well. Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole, but not for pantoprazole. Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events, when under clopidogrel and PPI treatment at the same time. These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI (especially omeprazole) in the same year. In contrast, more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel. Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality, with high and moderate quality studies not reporting any association, rising concern about unmeasured confounders biasing the low quality studies. Thus, no definite evidence exists for an effect on mortality. Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding, combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.
The proton-pump inhibitor lansoprazole enhances amyloid beta production.

Science.gov (United States)

Badiola, Nahuai; Alcalde, Victor; Pujol, Albert; Münter, Lisa-Marie; Multhaup, Gerd; Lleó, Alberto; Coma, Mireia; Soler-López, Montserrat; Aloy, Patrick

2013-01-01

A key event in the pathogenesis of Alzheimer's disease (AD) is the accumulation of amyloid-β (Aβ) species in the brain, derived from the sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Based on a systems biology study to repurpose drugs for AD, we explore the effect of lansoprazole, and other proton-pump inhibitors (PPIs), on Aβ production in AD cellular and animal models. We found that lansoprazole enhances Aβ37, Aβ40 and Aβ42 production and lowers Aβ38 levels on amyloid cell models. Interestingly, acute lansoprazole treatment in wild type and AD transgenic mice promoted higher Aβ40 levels in brain, indicating that lansoprazole may also exacerbate Aβ production in vivo. Overall, our data presents for the first time that PPIs can affect amyloid metabolism, both in vitro and in vivo.
Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological exploitations.

Science.gov (United States)

Sun, Jingjing; Deng, Ziqing; Yan, Aixin

2014-10-17

Multidrug resistance (MDR) refers to the capability of bacterial pathogens to withstand lethal doses of structurally diverse drugs which are capable of eradicating non-resistant strains. MDR has been identified as a major threat to the public health of human being by the World Health Organization (WHO). Among the four general mechanisms that cause antibiotic resistance including target alteration, drug inactivation, decreased permeability and increased efflux, drug extrusion by the multidrug efflux pumps serves as an important mechanism of MDR. Efflux pumps not only can expel a broad range of antibiotics owing to their poly-substrate specificity, but also drive the acquisition of additional resistance mechanisms by lowering intracellular antibiotic concentration and promoting mutation accumulation. Over-expression of multidrug efflux pumps have been increasingly found to be associated with clinically relevant drug resistance. On the other hand, accumulating evidence has suggested that efflux pumps also have physiological functions in bacteria and their expression is subject tight regulation in response to various of environmental and physiological signals. A comprehensive understanding of the mechanisms of drug extrusion, and regulation and physiological functions of efflux pumps is essential for the development of anti-resistance interventions. In this review, we summarize the development of these research areas in the recent decades and present the pharmacological exploitation of efflux pump inhibitors as a promising anti-drug resistance intervention. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Quantum mechanical features of optically pumped CW FIR lasers

Science.gov (United States)

Seligson, D.; Leite, J. R. R.; Sanchez, A.; Feld, M. S.; Ducloy, M.

1977-01-01

Quantum mechanical predictions for the gain of an optically pumped CW FIR laser are presented for cases in which one or both of the pump and FIR transitions are pressure or Doppler broadened. The results are compared to those based on the rate equation model. Some of the quantum mechanical predictions are verified in CH3OH.
Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study

DEFF Research Database (Denmark)

Charlot, Mette; Grove, Erik; Hansen, Peter Riis

2011-01-01

OBJECTIVE: To examine the effect of proton pump inhibitors on adverse cardiovascular events in aspirin treated patients with first time myocardial infarction. DESIGN: Retrospective nationwide propensity score matched study based on administrative data. Setting All hospitals in Denmark. PARTICIPANTS...... analysis showed no increase in risk related to use of H(2) receptor blockers (1.04, 0.79 to 1.38; P=0.78). Conclusion In aspirin treated patients with first time myocardial infarction, treatment with proton pump inhibitors was associated with an increased risk of adverse cardiovascular events....
Design of a Mechanical NaK Pump for Fission Space Power

Science.gov (United States)

Mireles, Omar R.; Bradley, David E.; Godfroy, Thomas

2011-01-01

Alkali liquid metal cooled fission reactor concepts are under development for spaceflight power requirements. One such concept utilizes a sodium-potassium eutectic (NaK) as the primary loop working fluid, which has specific pumping requirements. Traditionally, electromagnetic linear induction pumps have been used to provide the required flow and pressure head conditions for NaK systems but they can be limited in performance, efficiency, and number of available vendors. The objective of the project was to develop a mechanical NaK centrifugal pump that takes advantages of technology advances not available in previous liquid metal mechanical pump designs. This paper details the design, build, and performance test of a mechanical NaK pump developed at NASA Marshall Space Flight Center. The pump was designed to meet reactor cooling requirements using commercially available components modified for high temperature NaK service.
Prolonged Treatment Duration is Required for Successful Helicobacter pylori Eradication with Proton Pump Inhibitor Triple Therapy in Canada

Directory of Open Access Journals (Sweden)

Carlo A Fallone

2013-01-01

Full Text Available BACKGROUND: Traditional seven-day proton pump inhibitor triple therapy for Helicobacter pylori eradication has recently shown disappointing results outside of Canada. Prolonging therapy may be associated with poorer compliance and, hence, may not have a better outcome in a real-world setting.
A randomized controlled trial of laparoscopic nissen fundoplication versus proton pump inhibitors for treatment of patients with chronic gastroesophageal reflux disease: One-year follow-up.

Science.gov (United States)

Anvari, Mehran; Allen, Christopher; Marshall, John; Armstrong, David; Goeree, Ron; Ungar, Wendy; Goldsmith, Charles

2006-12-01

A randomized controlled trial conducted in patients with gastroesophageal reflux disease compared optimized medical therapy using proton pump inhibitor (n = 52) with laparoscopic Nissen fundoplication (n = 52). Patients were monitored for 1 year. The primary end point was frequency of gastroesophageal reflux dis-ease symptoms. Surgical patients had improved symptoms, pH control, and overall quality of life health index after surgery at 1 year compared with the medical group. The overall gastroesophageal reflux disease symptom score at 1 year was unchanged in the medical patients, but improved in the surgical patients. Fourteen patients in the medical arm experienced symptom relapse requiring titration of the proton pump inhibitor dose, but 6 had satisfactory symptom remission. No surgical patients required additional treatment for symptom control. Patients controlled on long-term proton pump inhibitor therapy for chronic gastroesophageal reflux disease are excellent surgical candidates and should experience improved symptom control after surgery at 1 year.
Inhibition of the coated vesicle proton pump and labeling of a 17,000-dalton polypeptide by N,N'-dicyclohexylcarbodiimide

International Nuclear Information System (INIS)

Arai, H.; Berne, M.; Forgac, M.

1987-01-01

N,N'-Dicyclohexylcarbodiimide (DCCD) inhibits 100% of proton transport and 80-85% of (Mg2+)-ATPase activity in clathrin-coated vesicles. Half-maximum inhibition of proton transport is observed at 10 microM DCCD after 30 min. Although treatment of the coated vesicle (H+)-ATPase with DCCD has no effect on ATP hydrolysis in the detergent-solubilized state, sensitivity of proton transport and ATPase activity to DCCD is restored following reconstitution into phospholipid vesicles. In addition, treatment of the detergent-solubilized enzyme with DCCD followed by reconstitution gives a preparation that is blocked in both proton transport and ATP hydrolysis. These results suggest that although the coated vesicle (H+)-ATPase can react with DCCD in either a membrane-bound or detergent-solubilized state, inhibition of ATPase activity is only manifested when the pump is present in sealed membrane vesicles. To identify the subunit responsible for inhibition of the coated vesicle (H+)-ATPase by DCCD, we have labeled the partially purified enzyme with [ 14 C]DCCD. A single polypeptide of molecular weight 17,000 is labeled. The extremely hydrophobic nature of this polypeptide is indicated by its extraction with chloroform:methanol. The 17,000-dalton protein can be labeled to a maximum stoichiometry of 0.99 mol of DCCD/mol of protein with 100% inhibition of proton transport occurring at a stoichiometry of 0.15-0.20 mol of DCCD/mol of protein. Amino acid analysis of the chloroform:methanol extracted 17,000-dalton polypeptide reveals a high percentage of nonpolar amino acids. The similarity in properties of this protein and the DCCD-binding subunit of the coupling factor (H+)-ATPases suggests that the 17,000-dalton polypeptide may function as part of a proton channel in the coated vesicle proton pump
Performance Tests of a Mechanical Pump in Sodium Environment

Energy Technology Data Exchange (ETDEWEB)

Cho, Chungho; Kim, Jong-Man; Ko, Yung Joo; Kim, Byeongyeon; Cho, Youngil; Jung, Min-Hwan; Gam, Da-Young; Lee, Yong Bum; Jeong, Ji-Young; Kim, Jong-Bum [KAERI, Daejeon (Korea, Republic of)

2016-05-15

Water is often selected as a surrogate test fluid because it is not only cheap, easily available and easy to handle but also its important hydraulic properties (density and kinematic viscosity) are very similar to that of the sodium. Nevertheless, to ensure the performance, safety, and operability of major components before its installation in the SFR, a series of demonstration experiments of some components in sodium environment should be positively necessary. So, SFR NSSS System Design Division of Korea Atomic Energy Research Institute (KAERI) built various sodium experimental facilities, especially STELLA-1 in 2012. STELLA-1 (Sodium inTegral Effect test Loop for safety simuLation and Assessment) is a large-scale separated effect test facility for demonstrating the thermal-hydraulic performances of major components such as a Sodium-to-Sodium heat exchanger (DHX), Sodium-to-Air heat exchanger (AHX) of the decay heat removal system, and mechanical sodium pump of the primary heat transport system (PHTS). The mechanical pump in-sodium performance test was successfully performed with good reproducibility of the experiment and data to compare hydraulic characteristic of a mechanical pump in-water was collected. In effect of temperature variation on the pump pressure head, reduction of pump pressure head at 250℃ by 0.57% of that of 300℃ maybe the result of an increase in sodium viscosity by 13.6% according to operating temperature decrease by 50℃. Also, we confirmed that the more flywheel weight, the longer halving time and the more initial flow rate when the pump seized, the shorter halving time. The results of the mechanical pump performance test data in sodium environment will be used to compare with that of the in water environment after the evaluation of measurement uncertainty for tests.
Should patients prescribed long-term low-dose aspirin receive proton pump inhibitors? A systematic review and meta-analysis

NARCIS (Netherlands)

Tran-Duy, A.; Vanmolkot, F. H.; Joore, M. A.; Hoes, A. W.; Stehouwer, C. D. A.

2015-01-01

Background: Several clinical guidelines recommend the use of proton pump inhibitors (PPIs) in patients taking low-dose aspirin but report no or limited supporting data. We conducted a systematic review and meta-analysis to examine the effects of co-administration of PPIs in patients taking low-dose
Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.

Science.gov (United States)

Zeng, Wei-Zheng; Liu, Di-Shi; Liu, Lu; She, Liang; Wu, Long-Jun; Xu, Tian-Le

2015-09-15

Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system.

Protonation of key acidic residues is critical for the K⁺-selectivity of the Na/K pump.

Science.gov (United States)

Yu, Haibo; Ratheal, Ian M; Artigas, Pablo; Roux, Benoît

2011-09-11

The sodium-potassium (Na/K) pump is a P-type ATPase that generates Na(+) and K(+) concentration gradients across the cell membrane. For each hydrolyzed ATP molecule, the pump extrudes three Na(+) and imports two K(+) by alternating between outward- and inward-facing conformations that preferentially bind K(+) or Na(+), respectively. Remarkably, the selective K(+) and Na(+) binding sites share several residues, and how the pump is able to achieve the selectivity required for the functional cycle is unclear. Here, free energy-perturbation molecular dynamics (FEP/MD) simulations based on the crystal structures of the Na/K pump in a K(+)-loaded state (E2·P(i)) reveal that protonation of the high-field acidic side chains involved in the binding sites is crucial to achieving the proper K(+) selectivity. This prediction is tested with electrophysiological experiments showing that the selectivity of the E2P state for K(+) over Na(+) is affected by extracellular pH.
On interference of cumulative proton production mechanisms

International Nuclear Information System (INIS)

Braun, M.A.; Vechernin, V.V.

1993-01-01

The dynamical picture of the cumulative proton production in hA-collisions by means of diagram analysis with NN interaction described by a non-relativistic NN potential is considered. The contributions of the various mechanisms (spectator, direct and rescattering) for backward hemisphere proton production within the framework of this common approach is calculated. The emphasis is on the comparison of the relative contributions of these mechanisms for various angles, taking into account the interference of these contributions. Comparison with experimental data is also presented. (author)
Antitumor effect of combination of the inhibitors of two new oncotargets: proton pumps and reverse transcriptase.

Science.gov (United States)

Lugini, Luana; Sciamanna, Ilaria; Federici, Cristina; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Fais, Stefano

2017-01-17

Tumor therapy needs new approaches in order to improve efficacy and reduce toxicity of the current treatments. The acidic microenvironment and the expression of high levels of endogenous non-telomerase reverse transcriptase (RT) are common features of malignant tumor cells. The anti-acidic proton pump inhibitor Lansoprazole (LAN) and the non-nucleoside RT inhibitor Efavirenz (EFV) have shown independent antitumor efficacy. LAN has shown to counteract drug tumor resistance. We tested the hypothesis that combination of LAN and EFV may improve the overall antitumor effects. We thus pretreated human metastatic melanoma cells with LAN and then with EFV, both in 2D and 3D spheroid models. We evaluated the treatment effect by proliferation and cell death/apoptosis assays in classical and in pulse administration experiments. The action of EFV was negatively affected by the tumor microenvironmental acidity, and LAN pretreatment overcame the problem. LAN potentiated the cytotoxicity of EFV to melanoma cells and, when administered during the drug interruption period, prevented the replacement of tumor cell growth.This study supports the implementation of the current therapies with combination of Proton Pumps and Reverse Transcriptase inhibitors.
Positive Darwinian selection in the piston that powers proton pumps in complex I of the mitochondria of Pacific salmon.

Science.gov (United States)

Garvin, Michael R; Bielawski, Joseph P; Gharrett, Anthony J

2011-01-01

The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.
Positive Darwinian Selection in the Piston That Powers Proton Pumps in Complex I of the Mitochondria of Pacific Salmon

Science.gov (United States)

Garvin, Michael R.; Bielawski, Joseph P.; Gharrett, Anthony J.

2011-01-01

The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm. PMID:21969854
Association between Proton Pump Inhibitors and Respiratory Infections: A Systematic Review and Meta-Analysis of Clinical Trials

Directory of Open Access Journals (Sweden)

Nabil Sultan

2008-01-01

Full Text Available BACKGROUND: Proton pump inhibitors (PPIs have become the mainstay of treatment for and prevention of many serious gastrointestinal diseases. Laboratory and clinical evidence suggests that the increase in gastric pH caused by PPIs may be linked to increased bacterial colonization of the stomach and may predispose patients to an increased risk for respiratory infections.
Hyperparathyroidism Associated with Long-Term Proton Pump Inhibitors Independent of Concurrent Bisphosphonate Therapy in Elderly Adults.

Science.gov (United States)

Hinson, Andrew M; Wilkerson, Bekka M; Rothman-Fitts, Ivy; Riggs, Ann T; Stack, Brendan C; Bodenner, Donald L

2015-10-01

To measure the effect of proton pump inhibitors (PPIs), with and without concurrent bisphosphonates, on parathyroid hormone (PTH), vitamin D, and calcium. Retrospective chart review of individuals 60 years and older. Subjects with reduced renal function (creatinine >1.3 mg/dL) and low vitamin D (hyperparathyroidism regardless of concurrent oral BP administration. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.
Pumping mechanisms in sputter-ion pumps low pressure operation

International Nuclear Information System (INIS)

Welch, K.M.

1991-01-01

It is shown that significant H 2 pumping occurs in the walls of triode pumps. Also, H 2 is pumped in the anode cells of sputter-ion pumps. This pumping occurs in a manner similar to that by which the inert gases are pumped. That is, H 2 is pumped in the walls of the anode cells by high energy neutral burial. Hydrogen in the pump walls and anodes limits the base pressure of the pump
Pumping mechanisms in sputter-ion pumps low pressure operation

International Nuclear Information System (INIS)

Welch, K.M.

1991-01-01

It is shown that significant H 2 pumping occurs in the walls of triode pumps. Also, H 2 is pumped in the anode cells of sputter-ion pumps. This pumping occurs in a manner similar to that by which the inert gases are pumped. That is, H 2 pumped in the walls of the anode cells by high energy neutral burial. Hydrogen in the pump walls and anodes limits the base pressure of the pump. 13 refs., 5 figs., 1 tab
Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine.

Science.gov (United States)

El Rouby, Nihal; Lima, John J; Johnson, Julie A

2018-04-01

Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism. Areas covered: This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism. Additionally, the role of CYP2C19 genetic variability in the therapeutic effectiveness or outcomes of PPI therapy is highlighted in details, to provide supporting evidence for the potential value of CYP2C19 genotype-guided approaches to PPI drug therapy. Expert opinion: There is a large body of evidence describing the impact of CYP2C19 variability on PPIs and its potential role in individualizing PPI therapy, yet, CYP2C19 pharmacogenetics has not been widely implemented into clinical practice. More data are needed but CYP2C19 genotype-guided dosing of PPIs is likely to become increasingly common and is expected to improve clinical outcomes, and minimize side effects related to PPIs.
The Role of Proton Pump Inhibitors in the Management of Pediatric Eosinophilic Esophagitis

Directory of Open Access Journals (Sweden)

Carolina Gutiérrez-Junquera

2018-05-01

Full Text Available Eosinophilic esophagitis (EoE is a chronic, local, immune-mediated disorder characterized by symptoms of esophageal dysfunction and the presence of a dense eosinophilic infiltrate in the esophageal mucosa. Consensus diagnostic recommendations for EoE diagnosis included absence of histological response to a proton-pump inhibitor (PPI trial, to exclude gastro-oesophageal reflux disease (GERD-associated esophagitis. This recommendation exposed an entity known as “proton pump inhibitor-responsive esophageal eosinophilia” (PPI-REE, which refers to patients with EoE phenotype who are PPI-responsive and do not present GERD. In recent years, there is evidence which indicates that PPI-REE is a sub-phenotype of EoE with similar clinical, endoscopic, histological and genetic characteristics, as well as Th2-related inflammatory response. As a result, PPIs should be considered another treatment for EoE and not a diagnostic tool. PPI-REE was originally described in a case series which included two children and in two retrospective pediatric series. Later, a prospective pediatric study showed a high rate of response to PPIs at high doses with long-term maintenance at lower doses. PPI monotherapy in children with esophageal eosinophilia (EE has been observed to reduce eotaxin-3 expression in epithelial cells and to practically reverse the allergy and inflammatory transcriptome. These data reveal that PPIs are also an effective treatment for EoE in pediatric patients, although more studies are necessary in order to define the best induction and maintenance treatment regimen, the long-term safety profile and their influence on the occurrence of fibrosis and esophageal remodeling.
Asymmetric Functional Conversion of Eubacterial Light-driven Ion Pumps*

Science.gov (United States)

Inoue, Keiichi; Nomura, Yurika; Kandori, Hideki

2016-01-01

In addition to the well-known light-driven outward proton pumps, novel ion-pumping rhodopsins functioning as outward Na+ and inward Cl− pumps have been recently found in eubacteria. They convert light energy into transmembrane electrochemical potential difference, similar to the prototypical archaeal H+ pump bacteriorhodopsin (BR) and Cl− pump halorhodopsin (HR). The H+, Na+, and Cl− pumps possess the conserved respective DTE, NDQ, and NTQ motifs in the helix C, which likely serve as their functional determinants. To verify this hypothesis, we attempted functional interconversion between selected pumps from each category by mutagenesis. Introduction of the proton-pumping motif resulted in successful Na+ → H+ functional conversion. Introduction of the respective characteristic motifs with several additional mutations leads to successful Na+ → Cl− and Cl− → H+ functional conversions, whereas remaining conversions (H+ → Na+, H+ → Cl−, Cl− → Na+) were unsuccessful when mutagenesis of 4–6 residues was used. Phylogenetic analysis suggests that a H+ pump is the common ancestor of all of these rhodopsins, from which Cl− pumps emerged followed by Na+ pumps. We propose that successful functional conversions of these ion pumps are achieved exclusively when mutagenesis reverses the evolutionary amino acid sequence changes. Dependence of the observed functional conversions on the direction of evolution strongly suggests that the essential structural mechanism of an ancestral function is retained even after the gain of a new function during natural evolution, which can be evoked by a few mutations. By contrast, the gain of a new function needs accumulation of multiple mutations, which may not be easily reproduced by limited mutagenesis in vitro. PMID:26929409
Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

International Nuclear Information System (INIS)

Becker, Jan C.; Grosser, Nina; Waltke, Christian; Schulz, Stephanie; Erdmann, Kati; Domschke, Wolfram; Schroeder, Henning; Pohle, Thorsten

2006-01-01

Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection
Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Becker, Jan C [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Grosser, Nina [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Waltke, Christian [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Schulz, Stephanie [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Erdmann, Kati [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Domschke, Wolfram [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Schroeder, Henning [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Pohle, Thorsten [Department of Medicine B, University of Muenster, 48149 Muenster (Germany)

2006-07-07

Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection.
BENEFITS VERSUS RISKS OF PROTON PUMP INHIBITORS: ARE WE OPENING THE CAN OF WORMS

Directory of Open Access Journals (Sweden)

Naser Ashraf Tadvi

2016-01-01

Full Text Available Proton pump inhibitors (PPIs are one of the most commonly used drugs worldwide They are indicated for treatment of Gastro-esophageal Reflux Disease (GERD, acid peptic disorders, stress ulcers and prophylaxis of NSAID induced ulcers.[1] PPIs are more efficacious than other drugs like histamine -2 receptor blockers for the treatment of these disorders.[1] Though PPIs are highly potent and effective acid suppressors they are often misused and prescribed irrationally. The incidence of irrational use of PPIs varies from 40-70 % in different studies. [2] In one of our previous studies 58 % of PPIs prescriptions were irrational. [2] These findings become much more significant in the light of recent findings which suggest correlation of long term use of PPIs to myocardial infarction and kidney injury. [3,4] The PPIs may be deemed safe for short term use but chronic use carries risk of hip fractures, infection with clostridium difficle, community acquired pneumonia.[2] PPIs exposure in elderly population was also found to be associated with hyperparathyroidism in one recently conducted study.[5] The ongoing long term studies for assessing the safety and association of PPIs with various serious outcomes may open up a new can of worms. Keeping in mind the benefits as well as risks of proton pump inhibitors, clinicians should judiciously use these drugs in practice. The patients should also be educated regarding the adverse outcomes of PPIs on long term therapy as these drugs are easily available without prescription.
Effect of long-term proton pump inhibitor administration on gastric mucosal atrophy: A meta-analysis

Science.gov (United States)

Li, Zhong; Wu, Cong; Li, Ling; Wang, Zhaoming; Xie, Haibin; He, Xiaozhou; Feng, Jin

2017-01-01

Background/Aims: Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related gastrointestinal diseases. Recently, some studies have reported that PPIs can alter the gastric mucosal architecture; however, the relationship remains controversial. This meta-analysis study was designed to quantify the association between long-term PPI administration and gastric atrophy. Materials and Methods: A PubMed search was conducted to identify studies using the keywords proton pump inhibitors or PPI and gastric atrophy or atrophic gastritis; the timeframe of publication searched was up to May 2016. Heterogeneity among studies was tested with the Q test; odds ratios (OR) and 95% confidence intervals (CI) were calculated. P values were calculated by I2 tests and regarded as statistically significant when <0.05. Results: We identified 13 studies that included 1465 patients under long-term PPI therapy and 1603 controls, with a total gastric atrophy rate of 14.50%. There was a higher presence of gastric atrophy (15.84%; statistically significant) in PPI group compared to the control group (13.29%) (OR: 1.55, 95% CI: 1.00–2.41). Conclusions: The pooled data suggest that long-term PPI use is associated with increased rates of gastric atrophy. Large-scale multicenter studies should be conducted to further investigate the relationship between acid suppressants and precancerous diseases. PMID:28721975
Positive Darwinian selection in the piston that powers proton pumps in complex I of the mitochondria of Pacific salmon.

Directory of Open Access Journals (Sweden)

Michael R Garvin

Full Text Available The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.
Proton Pump Inhibitors in Gastroesophageal Reflux Disease: Friend or Foe.

Science.gov (United States)

Gyawali, C Prakash

2017-09-01

Proton pump inhibitor (PPI) use in gastroesophageal reflux disease (GERD) has been redefined, in light of recent advances highlighting GERD phenotypes that respond to PPIs, and fresh revelations of potential risks of long-term PPI therapy. Erosive esophagitis predicts excellent response to PPI therapy, but non-erosive reflux disease (NERD) with abnormal reflux parameters on ambulatory reflux monitoring also demonstrates a similar response. In contrast, response is suboptimal in the absence of abnormal reflux parameters. In this setting, if an alternate appropriate indication for PPI therapy does not coexist, risks may outweigh benefits of PPI therapy. Adverse events from long-term PPI therapy continue to be reported, most based on association rather than cause-and-effect. Appropriate indications need to be established before embarking on long-term PPI therapy. Future research will define true risks of long-term PPI therapy, and develop alternate management options for acid peptic diseases.
Proton pump inhibitors alter the composition of the gut microbiota.

Science.gov (United States)

Jackson, Matthew A; Goodrich, Julia K; Maxan, Maria-Emanuela; Freedberg, Daniel E; Abrams, Julian A; Poole, Angela C; Sutter, Jessica L; Welter, Daphne; Ley, Ruth E; Bell, Jordana T; Spector, Tim D; Steves, Claire J

2016-05-01

Proton pump inhibitors (PPIs) are drugs used to suppress gastric acid production and treat GI disorders such as peptic ulcers and gastro-oesophageal reflux. They have been considered low risk, have been widely adopted, and are often over-prescribed. Recent studies have identified an increased risk of enteric and other infections with their use. Small studies have identified possible associations between PPI use and GI microbiota, but this has yet to be carried out on a large population-based cohort. We investigated the association between PPI usage and the gut microbiome using 16S ribosomal RNA amplification from faecal samples of 1827 healthy twins, replicating results within unpublished data from an interventional study. We identified a significantly lower abundance in gut commensals and lower microbial diversity in PPI users, with an associated significant increase in the abundance of oral and upper GI tract commensals. In particular, significant increases were observed in Streptococcaceae. These associations were replicated in an independent interventional study and in a paired analysis between 70 monozygotic twin pairs who were discordant for PPI use. We propose that the observed changes result from the removal of the low pH barrier between upper GI tract bacteria and the lower gut. Our findings describe a significant impact of PPIs on the gut microbiome and should caution over-use of PPIs, and warrant further investigation into the mechanisms and their clinical consequences. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
The Performance test of Mechanical Sodium Pump with Water Environment

International Nuclear Information System (INIS)

Cho, Chungho; Kim, Jong-Man; Ko, Yung Joo; Jeong, Ji-Young; Kim, Jong-Bum; Ko, Bock Seong; Park, Sang Jun; Lee, Yoon Sang

2015-01-01

As contrasted with PWR(Pressurized light Water Reactor) using water as a coolant, sodium is used as a coolant in SFR because of its low melting temperature, high thermal conductivity, the high boiling temperature allowing the reactors to operate at ambient pressure, and low neutron absorption cross section which is required to achieve a high neutron flux. But, sodium is violently reactive with water or oxygen like the other alkali metal. So Very strict requirements are demanded to design and fabricate of sodium experimental facilities. Furthermore, performance testing in high temperature sodium environments is more expensive and time consuming and need an extra precautions because operating and maintaining of sodium experimental facilities are very difficult. The present paper describes performance test results of mechanical sodium pump with water which has been performed with some design changes using water test facility in SAM JIN Industrial Co. To compare the hydraulic characteristic of model pump with water and sodium, the performance test of model pump were performed using vender's experimental facility for mechanical sodium pump. To accommodate non-uniform thermal expansion and to secure the operability and the safety, the gap size of some parts of original model pump was modified. Performance tests of modified mechanical sodium pump with water were successfully performed. Water is therefore often selected as a surrogate test fluid because it is not only cheap, easily available and easy to handle but also its important hydraulic properties (density and kinematic viscosity) are very similar to that of the sodium. Normal practice to thoroughly test a design or component before applied or installed in reactor is important to ensure the safety and operability in the sodium-cooled fast reactor (SFR). So, in order to estimate the hydraulic behavior of the PHTS pump of DSFR (600 MWe Demonstraion SFR), the performance tests of the model pump such as performance

Effect of proton-pump inhibitor treatment on symptoms and quality of life in GERD patients depends on the symptom-reflux association

NARCIS (Netherlands)

Aanen, Marissa C.; Weusten, Bas L. A. M.; Numans, Mattijs E.; de Wit, Niek J.; Samsom, Melvin; Smout, Andre J. P. M.

2008-01-01

Backgound: Gastroesophageal reflux disease patients demonstrate various pathophysiologic backgrounds. Therefore, a heterogeneous response to proton-pump inhibitor (PPI) treatment can be expected. We investigated the effect of short-term PPI treatment on symptoms and quality of life (QOL) in primary
Pancreatic bicarbonate secretion involves two proton pumps.

Science.gov (United States)

Novak, Ivana; Wang, Jing; Henriksen, Katrine L; Haanes, Kristian A; Krabbe, Simon; Nitschke, Roland; Hede, Susanne E

2011-01-07

Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium express H(+)/HCO(3)(-) transporters, which depend on gradients created by the Na(+)/K(+)-ATPase. However, the model cannot fully account for high-bicarbonate concentrations, and other active transporters, i.e. pumps, have not been explored. Here we show that pancreatic ducts express functional gastric and non-gastric H(+)-K(+)-ATPases. We measured intracellular pH and secretion in small ducts isolated from rat pancreas and showed their sensitivity to H(+)-K(+) pump inhibitors and ion substitutions. Gastric and non-gastric H(+)-K(+) pumps were demonstrated on RNA and protein levels, and pumps were localized to the plasma membranes of pancreatic ducts. Quantitative analysis of H(+)/HCO(3)(-) and fluid transport shows that the H(+)-K(+) pumps can contribute to pancreatic secretion in several species. Our results call for revision of the bicarbonate transport physiology in pancreas, and most likely other epithelia. Furthermore, because pancreatic ducts play a central role in several pancreatic diseases, it is of high relevance to understand the role of H(+)-K(+) pumps in pathophysiology.
Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients' bed.

Science.gov (United States)

Ferrari, Stefano; Perut, Francesca; Fagioli, Franca; Brach Del Prever, Adalberto; Meazza, Cristina; Parafioriti, Antonina; Picci, Piero; Gambarotti, Marco; Avnet, Sofia; Baldini, Nicola; Fais, Stefano

2013-10-24

Major goals in translational oncology are to reduce systemic toxicity of current anticancer strategies and improve effectiveness. An extremely efficient cancer cell mechanism to avoid and/or reduce the effects of highly cytotoxic drugs is the establishment of an acidic microenvironment, an hallmark of all malignant tumors. The H +-rich milieu that anticancer drugs meet once they get inside the tumor leads to their protonation and neutralization, therefore hindering their access into tumor cells. We have previously shown that proton pump inhibitors (PPI) may efficiently counterattack this tumor advantage leading to a consistent chemosensitization of tumors. In this study, we investigated the effects of PPI in chemosensitizing osteosarcoma. MG-63 and Saos-2 cell lines were used as human osteosarcoma models. Cell proliferation after pretreatment with PPI and subsequent treatment with cisplatin was evaluated by using erythrosin B dye vital staining. Tumour growth was evaluated in xenograft treated with cisplatin after PPI pretreatment. Subsequently, a multi-centre historically controlled trial, was performed to evaluate the activity of a pre-treatment administration of PPIs as chemosensitizers during neoadjuvant chemotherapy based on methotrexate, cisplatin, and adriamycin. Preclinical experiments showed that PPI sensitize both human osteosarcoma cell lines and xenografts to cisplatin. A clinical study subsequently showed that pretreatment with PPI drug esomeprazole leads to an increase in the local effect of chemotherapy, as expressed by percentage of tumor necrosis. This was particularly evident in chondroblastic osteosarcoma, an histological subtype that normally shows a poor histological response. Notably, no significant increase in toxicity was recorded in PPI treated patients. This study provides the first evidence that PPI may be beneficially added to standard regimens in combination to conventional chemotherapy.
Role of Acid and Weakly Acidic Reflux in Gastroesophageal Reflux Disease Off Proton Pump Inhibitor Therapy

OpenAIRE

Sung, Hea Jung; Cho, Yu Kyung; Moon, Sung Jin; Kim, Jin Su; Lim, Chul Hyun; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gye

2012-01-01

Background/Aims Available data about reflux patterns and symptom determinants in the gastroesophageal reflux disease (GERD) subtypes off proton pump inhibitor (PPI) therapy are lacking. We aimed to evaluate reflux patterns and determinants of symptom perception in patients with GERD off PPI therapy by impedance-pH monitoring. Methods We retrospectively reviewed the impedance-pH data in patients diagnosed as GERD based on results of impedance-pH monitoring, endoscopy and/or typical symptoms. T...
Polarized proton and deuteron targets for the usage in intensive proton beams

International Nuclear Information System (INIS)

Get'man, V.A.; Derkach, A.Ya.; Karnaukhov, I.M.; Lukhanin, A.A.; Razumnyj, A.A.; Sorokin, P.V.; Sporo, E.A.; Telegin, Yu.N.

1982-01-01

Polarized proton and deuteron targets are developed and tested for conducting investigations in intense photon beams. A flowsheet of polarization targets which includes: working agent of the target, superconducting magnet, cryostat of 3 He evaporation with 3 He pumping and recirculation systems, SHF system of 4 mm range for polarization pumping, measuring system of target polarization protons is presented. Working agent of the targets includes frozen balls with 1.5 mm diameter. Ethylene-glucol and 1.2-propylene-glycol were used as a working substance for proton targets. Completely deuterated ethylene-glycol was used for the deuteron target. Vertical magnetic field with 2.7 T intensity is produced by a superconducting magnetic system. Polarization pumping is exercised at 75 GHz frequency. Q-meter of direct current is used for determination of polarization. Working temperature of the cryostat is approximately 0.5 K. The lock device permits to exercise replacement of the target working agent during 30 minutes
Proton pump inhibitor-responsive chronic cough without acid reflux: a case report

Directory of Open Access Journals (Sweden)

Nobata Kouichi

2007-08-01

Full Text Available Abstract Background Because 24-h esophageal pH monitoring is quite invasive, the diagnosis of gastroesophageal reflux disease (GERD-associated cough has usually been made based merely on the clinical efficacy of treatment with proton pump inhibitor (PPI. Case presentation We recently encountered two patients with PPI-responsive chronic non-productive cough for whom switching from bronchodilators and glucocorticosteroids to PPI resulted in improvement of cough. The cough returned nearly to pre-administration level a few weeks after discontinuation of PPI. Though GERD-associated cough was suspected, 24-h esophageal pH monitoring revealed that the cough rarely involved gastric acid reflux. Following re-initiation of PPI, the cough disappeared again. Conclusion PPI may improve cough unrelated to gastric acid reflux.
Fast Flux Test Facility sodium pump operating experience - mechanical

International Nuclear Information System (INIS)

Buonamici, R.

1987-11-01

The Heat Transport System (HTS) pumps were designed, fabricated, tested, and installed in the Fast Flux Test Facility (FFTF) Plant during the period from September 1970 through July 1977. Since completion of the installation and sodium fill in December 1978, the FFTF Plant pumps have undergone extensive testing and operation with HTS testing and reactor operation. Steady-state hydraulic and mechanical performances have been and are excellent. In all, FFTF primary and secondary pumps have operated in sodium for approximately 75,000 hours and 79,000 hours, respectively, to August 24, 1987
Conceptual design and related R and D on ITER mechanical based primary pumping system

International Nuclear Information System (INIS)

Tanzawa, Sadamitsu; Hiroki, Seiji; Abe, Tetsuya; Shimizu, Katsusuke; Inoue, Masahiko; Watanabe, Mitsunori; Iguchi, Masashi; Sugimoto, Tomoko; Inohara, Takashi; Nakamura, Jun-ichi

2008-12-01

The primary vacuum pumping system of the International Thermonuclear Experimental Reactor (ITER) exhausts a helium (He) ash resulting from the DT-burn with excess DT fueling gas, as well as performing a variety of functions such as pump-down, leak testing and wall conditioning. A mechanical based vacuum pumping system has some merits of a continuous pumping, a much lower tritium inventory, a lower operational cost and easy maintenance, comparing with a cryopump system, although demerits of an indispensable magnetic shield and insufficient performance for hydrogen (H 2 ) pumping is are well recognized. To overcome the demerits, we newly fabricated and tested a helical grooved pump (HGP) unit suitable for H 2 pumping at the ITER divertor pressure of 0.1-10 Pa. Through this R and D, we successfully established many design and manufacturing databases of large HGP units for the lightweight gas pumping. Based on the databases, we conceptually designed the ITER vacuum pumping system mainly comprising the HGP with an optimal pump unit layout and a magnetic shield. We also designed conceptually the reduced cost (RC)-ITER pumping system, where a compound molecular pump combining turbine bladed rotors and helical grooved ones was mainly used. The ITER mechanical based primary pumping system proposed has eventually been a back-up solution, whereas a cryopump based one was formally selected to the ITER for construction. The mechanical pumps are increasingly used in many areas with well sophisticated performance, so we believe that fusion reactors of subsequent prototype ones will select the mechanical based pumping system due to primarily a high operational reliability and a cost melt. (author)
The potential drug-drug interaction between proton pump inhibitors and warfarin

DEFF Research Database (Denmark)

Henriksen, Daniel Pilsgaard; Stage, Tore Bjerregaard; Hansen, Morten Rix

2015-01-01

BACKGROUND: Proton pump inhibitors (PPIs) have been suggested to increase the effect of warfarin, and clinical guidelines recommend careful monitoring of international normalized ratio (INR) when initiating PPI among warfarin users. However, this drug-drug interaction is sparsely investigated...... in a clinical setting. The aim was to assess whether initiation of PPI treatment among users of warfarin leads to increased INR values. METHODS: The study was an observational self-controlled study from 1998 to 2012 leveraging data on INR measurements on patients treated with warfarin from primary care...... and outpatient clinics and their use of prescription drugs. Data were analyzed in 2015. We assessed INR, warfarin dose, and dose/INR ratio before and after initiating PPI treatment using the paired student's t-test. RESULTS: We identified 305 warfarin users initiating treatment with PPIs. The median age was 71...
Proton pump inhibitor responders who are not confirmed as GERD patients with impedance and pH monitoring: who are they?

NARCIS (Netherlands)

de Bortoli, N.; Martinucci, I.; Savarino, E.; Bellini, M.; Bredenoord, A. J.; Franchi, R.; Bertani, L.; Furnari, M.; Savarino, V.; Blandizzi, C.; Marchi, S.

2014-01-01

A short-course of proton pump inhibitors (PPIs) is often used to confirm gastroesophageal reflux disease (GERD). However, some patients with PPI responsive heartburn do not seem to have evidence of GERD on impedance-pH monitoring (MII-pH). The aim of the study was to evaluate patients with reflux
Ekman pumping mechanism driving precipitation anomalies in response to equatorial heating

Science.gov (United States)

Hamouda, Mostafa E.; Kucharski, Fred

2018-03-01

In this paper some basic mechanisms for rainfall teleconnections to a localized tropical sea surface temperature anomaly are re-visited using idealized AGCM aqua-planet simulations. The dynamical response is generally in good agreement with the Gill-Matsuno theory. The mechanisms analyzed are (1) the stabilization of the tropical troposphere outside the heating region, (2) the Walker circulation modification and (3) Ekman pumping induced by the low-level circulation responses. It is demonstrated that all three mechanisms, and in particular (2) and (3), contribute to the remote rainfall teleconnections. However, mechanism (3) best coincides with the overall horizontal structure of rainfall responses. It is shown by using the models boundary layer parameterization that low-level vertical velocities are indeed caused by Ekman pumping and that this induces vertical velocities in the whole tropospheric column through convective feedbacks. Also the modification of the responses due to the presence of idealized warm pools is investigated. It is shown that warm pools modify the speed of the tropical waves, consistent with Doppler shifts and are thus able to modify the Walker circulation adjustments and remote rainfall responses. The sensitivity of the responses, and in particular the importance of the Ekman pumping mechanism, to large variations in the drag coefficient is also tested, and it is shown that the Ekman pumping mechanism is robust for a wide range of values.
Association Between Proton Pump Inhibitors and Metronomic Capecitabine as Salvage Treatment for Patients With Advanced Gastrointestinal Tumors: A Randomized Phase II Trial.

Science.gov (United States)

Marchetti, Paolo; Milano, Annalisa; D'Antonio, Chiara; Romiti, Adriana; Falcone, Rosa; Roberto, Michela; Fais, Stefano

2016-12-01

The acidification of extracellular compartment represents a conceivable mechanism of drug resistance in malignant cells. In addition, it has been reported to drive proliferation and promote invasion and metastasis. Experimental evidence has shown that proton pump inhibitors can counteract tumor acidification and restore sensitivity to anticancer drugs. Moreover, early clinical data have supported the role of proton pump inhibitors in anticancer treatments. Metronomic capecitabine has demonstrated beneficial effects as salvage chemotherapy for heavily pretreated or frail patients with gastrointestinal cancer. The present study (EudraCT Number: 2013-001096-20) was aimed at investigating the activity and safety of high-dose rabeprazole in combination with metronomic capecitabine in patients with advanced gastrointestinal cancer refractory to standard treatment. A total of 66 patients will be randomized 1:1 to receive capecitabine 1500 mg/daily, continuously with or without rabeprazole 1.5 mg/kg twice a day, 3 days a week until disease progression, undue toxicity, or withdrawal of informed consent. The primary endpoint is progression-free survival. The secondary endpoints are clinical benefit, which reflects the proportion of patients with complete response, partial response, and stable disease, and overall survival. Progression-free and overall survival will be evaluated using a log-rank test to determine the effect of rabeprazole independently at the 2-sided α-level of 0.05. Other assessments will include the frequency and severity of adverse events and changes in laboratory parameters to measure the safety, and the pharmacokinetics of capecitabine. The results are expected in 2016. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Evaluation of potential interactions between mycophenolic acid derivatives and proton pump inhibitors.

Science.gov (United States)

Gabardi, Steven; Olyaei, Ali

2012-01-01

To evaluate the incidence of gastrointestinal (GI) complications in solid organ transplant (SOT) recipients, impact of the complications on transplant outcomes, and the potential interactions between mycophenolic acid (MPA) derivatives and proton pump inhibitors (PPIs). An unrestricted literature search (1980-January 2012) was performed with MEDLINE and EMBASE using the following key words: drug-drug interaction, enteric-coated mycophenolic acid, GI complications, mycophenolate mofetil, solid organ transplant, and proton pump inhibitor, including individual agents within the class. Abstracts from scientific meetings were also evaluated. Additionally, reference citations from identified publications were reviewed. Relevant English-language, original research articles and review articles were evaluated if they focused on any of the topics identified in the search or included substantial content addressing GI complications in SOT recipients or drug interactions. GI complications are frequent among SOT recipients, with some studies showing prevalence rates as high as 70%. Transplant outcomes among renal transplant recipients are significantly impacted by GI complications, especially in patients requiring immunosuppressant dosage reductions or premature discontinuation. To this end, PPI use among patients receiving transplants is common. Recent data demonstrate that PPIs significantly reduce the overall exposure to MPA after oral administration of mycophenolate mofetil. Similar studies show this interaction does not exist between PPIs and enteric-coated mycophenolic acid (EC-MPA). Unfortunately, most of the available data evaluating this interaction are pharmacokinetic analyses that do not investigate the clinical impact of this interaction. A significant interaction exists between PPIs and mycophenolate mofetil secondary to reduced dissolution of mycophenolate mofetil in higher pH environments. EC-MPA is not absorbed in the stomach; therefore, low intragastric acidity
Delirium in the geriatric unit: proton-pump inhibitors and other risk factors

Directory of Open Access Journals (Sweden)

Otremba I

2016-04-01

Full Text Available Iwona Otremba, Krzysztof Wilczyński, Jan SzewieczekDepartment of Geriatrics, School of Health Sciences in Katowice, Medical University of Silesia, Katowice, PolandBackground: Delirium remains a major nosocomial complication of hospitalized elderly. Predictive models for delirium may be useful for identification of high-risk patients for implementation of preventive strategies.Objective: Evaluate specific factors for development of delirium in a geriatric ward setting.Methods: Prospective cross-sectional study comprised 675 consecutive patients aged 79.2±7.7 years (66% women and 34% men, admitted to the subacute geriatric ward of a multiprofile university hospital after exclusion of 113 patients treated with antipsychotic medication because of behavioral disorders before admission. Comprehensive geriatric assessments including a structured interview, physical examination, geriatric functional assessment, blood sampling, ECG, abdominal ultrasound, chest X-ray, Confusion Assessment Method for diagnosis of delirium, Delirium-O-Meter to assess delirium severity, Richmond Agitation-Sedation Scale to assess sedation or agitation, visual analog scale and Doloplus-2 scale to assess pain level were performed.Results: Multivariate logistic regression analysis revealed five independent factors associated with development of delirium in geriatric inpatients: transfer between hospital wards (odds ratio [OR] =2.78; confidence interval [CI] =1.54–5.01; P=0.001, preexisting dementia (OR =2.29; CI =1.44–3.65; P<0.001, previous delirium incidents (OR =2.23; CI =1.47–3.38; P<0.001, previous fall incidents (OR =1.76; CI =1.17–2.64; P=0.006, and use of proton-pump inhibitors (OR =1.67; CI =1.11–2.53; P=0.014.Conclusion: Transfer between hospital wards, preexisting dementia, previous delirium incidents, previous fall incidents, and use of proton-pump inhibitors are predictive of development of delirium in the geriatric inpatient setting.Keywords: delirium
Damage effects and mechanisms of proton irradiation on methyl silicone rubber

International Nuclear Information System (INIS)

Zhang, L.X.; He, Sh.Y.; Xu, Zh.; Wei, Q.

2004-01-01

A study was performed on the damage effects and mechanisms of proton irradiation with 150 keV energy to space-grade methyl silicone rubber. The changes in surface morphology, mechanical properties, infrared attenuated total reflection (ATR) spectrum, mass spectrum and pyrolysis gas chromatography-mass spectrum (PYGC-MS) indicated that, under lower fluence, the proton radiation would induce cross-linking effect, resulting in an increase in tensile strengths and hardness of the methyl silicon rubber. However, under higher proton fluence, the radiation-induced degradation, which decreased the tensile strengths and hardness, became a dominant effect. A macromolecular-network destruction model for the silicone rubber radiated with the protons was proposed
Treatment of gastro-oesophageal reflux disease with rabeprazole in primary and secondary care : does Helicobacter pylori infection affect proton pump inhibitor effectiveness?

NARCIS (Netherlands)

de Wit, NJ; de Boer, WA; Geldof, H; Hazelhoff, B; Bergmans, P; Tytgat, GNJ; Smout, AJPM

2004-01-01

Background: The presence of the gastric pathogen, Helicobacter pylori influences acid suppression by proton pump inhibitors and treatment outcome in patients with gastro-oesophageal reflux disease. Aim: To determine the influence of H. pylori infection on effectiveness of rabeprazole in primary and
Treatment of gastro-oesophageal reflux disease with rabeprazole in primary and secondary care: does Helicobacter pylori infection affect proton pump inhibitor effectiveness?

NARCIS (Netherlands)

Wit, N. J.; Boer, W. A.; Geldof, H.; Hazelhoff, B.; Bergmans, P.; Tytgat, G. N. J.; Smout, A. J. P. M.

2004-01-01

BACKGROUND: The presence of the gastric pathogen, Helicobacter pylori influences acid suppression by proton pump inhibitors and treatment outcome in patients with gastro-oesophageal reflux disease. AIM: To determine the influence of H. pylori infection on effectiveness of rabeprazole in primary and
Incremental cost-effectiveness of proton pump inhibitors for the prevention of NSAID ulcers: a pharmacoeconomic analysis linked to a case-control study.

NARCIS (Netherlands)

Vonkeman, Harald Erwin; Braakman-Jansen, Louise Marie Antoinette; Klok, Rogier M.; Postma, Maarten J.; Brouwers, Jacobus R.B.J.; van de Laar, Mart A F J

2008-01-01

Introduction We estimated the cost effectiveness of concomitant proton pump inhibitors (PPIs) in relation to the occurrence of non-steroidal anti-inflammatory drug (NSAID) ulcer complications. Methods This study was linked to a nested case-control study. Patients with NSAID ulcer complications were
Multi technical analysis of wear mechanisms in axial piston pumps

Science.gov (United States)

Schuhler, G.; Jourani, A.; Bouvier, S.; Perrochat, J.-M.

2017-05-01

Axial piston pumps convert a motor rotation motion into hydraulic or pneumatic power. Their compactness and efficiency of approximately 0.9 make them suitable for actuation applications especially in aeronautics. However, they suffer a limited life due to the wear of their components. In the literature, studies of axial piston pumps deal with contact between its different elements under lubrication conditions. Nevertheless, they are more focused on analytic or numerical approaches. This study consists in an experimental analysis of worn pump components to highlight and understand wear mechanisms. Piston shoes are central components in the axial piston pump since they are involved in three tribological contacts. These three contacts are thereby studied: piston shoes/swashplate, piston shoes/pistons and piston shoes/shoes hold down plate (SHDP). To perform this analysis, helicopter hydraulic pumps after different operating times have been studied. The wear damage mechanisms and wear debris are analysed using SEM observations. 3D surface roughness measurements are then used to characterize worn surfaces. The observations reveal that in the contact between shoes and swashplate, the main wear mechanism is three-body abrasive wear due to coarse carbides removal. Between shoes and pistons, wear occurs in a less severe way and is mainly due to the debris generated in the first contact and conveyed by the lubricating fluid. In the third contact, the debris are also the prime cause of the abrasive wear and the generation of deep craters in the piston shoes.
Lack of Association Between Proton Pump Inhibitor Use and Cognitive Decline

DEFF Research Database (Denmark)

Wod, Mette; Hallas, Jesper; Andersen, Kjeld

2018-01-01

from surveys of middle-aged individuals (46-67 years old; the Middle Aged Danish Twin study) and older individuals (the Longitudinal Study of Aging Danish Twins) who underwent cognitive assessments (a 5-component test battery) over a 10-year period (middle-age study, n=2346) or a 2-year period...... PPI use and a composite score of cognitive function at baseline and decreases in scores during the follow-up periods. RESULTS: Use of PPIs before study enrollment was associated with a slightly lower mean cognitive score at baseline in the middle age study. The adjusted difference in mean score......BACKGROUND & AIMS: Studies of association between use of proton pump inhibitors (PPI) and dementia have yielded conflicting results. We investigated the effects of PPIs on cognitive decline in a study of middle-aged and elderly twins in Denmark. METHODS: In a prospective study, we collected data...

Cost-Effectiveness of Intravenous Proton Pump Inhibitors in High-Risk Bleeders

Directory of Open Access Journals (Sweden)

Sander Veldhuyzen van Zanten

2004-01-01

Full Text Available There is unequivocal evidence that proton pump inhibitors (PPIs are currently the most effective acid suppressive agents available. Intravenous (IV formulations have been developed, although only IV pantoprazole is available in Canada. In patients presenting with serious upper gastrointestinal (GI bleeding due to duodenal or gastric ulcers, it has always been believed that IV administration of acid-lowering agents would improve clinical outcomes. The reason behind this thinking is twofold. First, there is in vitro evidence that formed clots are more stable at or near neutral pH (1. Second, by administering the agent intravenously, suppression of acid production is achieved much more quickly, thereby promoting more rapid healing of the ulcer and reducing the risk of persistent or recurrent bleeding. Interestingly and surprisingly, however, the data for intravenous H2-blockers have been disappointing (2. This failure to demonstrate clinical benefit has never been fully explained.
Practical considerations in the management of proton-pump inhibitors

Directory of Open Access Journals (Sweden)

Lara Aguilera-Castro

Full Text Available Proton-pump inhibitors (PPIs are one of the most active ingredients prescribed in Spain. In recent decades there has been an overuse of these drugs in both outpatient clinics and hospitals that has lead to a significant increase in healthcare spending and to an increase in the risk of possible side effects. It is important for health professionals to know the accepted indications and the correct doses for the use of these drugs. On the market there are different types of PPI: omeprazole, pantoprazole, lansoprazole, rabeprazole and esomeprazole. Omeprazole is the oldest and most used PPI, being also the cheapest. Although there are no important differences between PPIs in curing diseases, esomeprazole, a new-generation PPI, has proved to be more effective in eradicating H. pylori and in healing severe esophagitis compared to other PPIs. In recent years the use of generic drugs has spread; these drugs have the same bioavailability than the original drugs. In the case of PPIs, the few comparative studies available in the literature between original and generic drugs have shown no significant differences in clinical efficacy.
FEATURES OF LONG-TERM MECHANICAL CIRCULATORY SUPPORT WITH CONTINUOUS-FLOW PUMP

Directory of Open Access Journals (Sweden)

G. P. Itkin

2012-01-01

Full Text Available In a review of the comparative analysis of methods and tools for long-term mechanical circulatory support with continuous flow and pulsatile flow implantable pumps. Particular attention is paid to the choice of the optimal modes of the operation of pumps based on the physical principles of the interaction between a the steady flow of blood to the pulsatile mechanics of the heart chambers.
Obscure bleeding colonic duplication responds to proton pump inhibitor therapy.

Science.gov (United States)

Jacques, Jérémie; Projetti, Fabrice; Legros, Romain; Valgueblasse, Virginie; Sarabi, Matthieu; Carrier, Paul; Fredon, Fabien; Bouvier, Stéphane; Loustaud-Ratti, Véronique; Sautereau, Denis

2013-09-21

We report the case of a 17-year-old male admitted to our academic hospital with massive rectal bleeding. Since childhood he had reported recurrent gastrointestinal bleeding and had two exploratory laparotomies 5 and 2 years previously. An emergency abdominal computed tomography scan, gastroscopy and colonoscopy, performed after hemodynamic stabilization, were considered normal. High-dose intravenous proton pump inhibitor (PPI) therapy was initiated and bleeding stopped spontaneously. Two other massive rectal bleeds occurred 8 h after each cessation of PPI which led to a hemostatic laparotomy after negative gastroscopy and small bowel capsule endoscopy. This showed long tubular duplication of the right colon, with fresh blood in the duplicated colon. Obscure lower gastrointestinal bleeding is a difficult medical situation and potentially life-threatening. The presence of ulcerated ectopic gastric mucosa in the colonic duplication explains the partial efficacy of PPI therapy. Obscure gastrointestinal bleeding responding to empiric anti-acid therapy should probably evoke the diagnosis of bleeding ectopic gastric mucosa such as Meckel's diverticulum or gastrointestinal duplication, and gastroenterologists should be aware of this potential medical situation.
Optical-response properties in an atom-assisted optomechanical system with a mechanical pump

Science.gov (United States)

Sun, Xue-Jian; Chen, Hao; Liu, Wen-Xiao; Li, Hong-Rong

2017-05-01

We investigate the optical-response properties of a coherent-mechanical pumped optomechanical system (OMS) coupled to a Λ-type three-level atomic ensemble. Due to the optomechanical and the cavity-atom couplings, the optomechanically induced transparency (OMIT) and electromagnetically induced transparency (EIT) phenomena could both be observed from our proposal. In the presence of a coherent mechanical pump, we show that the OMIT behavior of the probe field exhibits a phase-dependent effect, leading to the switch from OMIT to optomechanically induced absorption or amplification, while the feature of EIT remains unchanged. The distinctly different effects of the mechanical pump on OMIT and EIT behavior assure us that the absorption (amplification) and transparency of the output probe field can be simultaneously observed. Moreover, a tunable switch from slow to fast light can also be realized by tuning the phase and amplitude of the mechanical pump. In particular, the presence of the atomic ensemble can further adjust the group delay, providing additional flexibility for achieving the tunable switch.
Unexplained abdominal pain as a driver for inappropriate therapeutics: an audit on the use of intravenous proton pump inhibitors

OpenAIRE

Pauline Siew Mei Lai; Yin Yen Wong; Yong Chia Low; Hui Ling Lau; Kin-Fah Chin; Sanjiv Mahadeva

2014-01-01

Background. Proton pump inhibitors (PPIs) are currently the most effective agents for acid-related disorders. However, studies show that 25–75% of patients receiving intravenous PPIs had no appropriate justification, indicating high rates of inappropriate prescribing. Objective. To examine the appropriate use of intravenous PPIs in accordance with guidelines and the efficacy of a prescribing awareness intervention at an Asian teaching institution. Setting. Prospective audit in a tertiary hosp...
Gastroesophageal reflux symptoms not responding to proton pump inhibitor: GERD, NERD, NARD, esophageal hypersensitivity or dyspepsia?

Science.gov (United States)

Bashashati, Mohammad; Hejazi, Reza A; Andrews, Christopher N; Storr, Martin A

2014-01-01

Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy. PMID:24719900
Advanced design of the Mechanical Tritium Pumping System for JET DTE2

International Nuclear Information System (INIS)

Giegerich, T.; Bekris, N.; Camp, P.; Day, Chr.; Gethins, M.; Lesnoy, S.; Luo, X.; Müller, R.; Ochoa, S.; Pfeil, P.; Smith, R.; Strobel, H.; Stump, H.

2016-01-01

For tritium processing in JET during the next Deuterium-Tritium-Experiment (DTE2), a fully tritium compatible and continuously working vacuum pumping system has been developed. This pump train will be used as roughing pump to cover a pressure regime between 10 −1 Pa and ambient pressure. Therefore, a two-stage liquid ring pump in combination with a booster vapor diffusion pump will be applied. In this paper, a close-to-final design of the pumps is being described. Finite element (FEM) simulation results of components where high mechanical stresses due to thermal gradients are expected are presented. Furthermore, the final design of the control and data acquisition system is shown and explained.
Advanced design of the Mechanical Tritium Pumping System for JET DTE2

Energy Technology Data Exchange (ETDEWEB)

Giegerich, T., E-mail: thomas.giegerich@kit.edu [Karlsruhe Institute of Technology (KIT), Institute for Technical Physics, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Bekris, N. [EUROfusion Program Management Unit (PMU), ITER Physics Department, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Camp, P. [CCFE, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Day, Chr. [Karlsruhe Institute of Technology (KIT), Institute for Technical Physics, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Gethins, M.; Lesnoy, S. [CCFE, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Luo, X.; Müller, R.; Ochoa, S.; Pfeil, P. [Karlsruhe Institute of Technology (KIT), Institute for Technical Physics, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Smith, R. [CCFE, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Strobel, H.; Stump, H. [Karlsruhe Institute of Technology (KIT), Institute for Technical Physics, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany)

2016-11-01

For tritium processing in JET during the next Deuterium-Tritium-Experiment (DTE2), a fully tritium compatible and continuously working vacuum pumping system has been developed. This pump train will be used as roughing pump to cover a pressure regime between 10{sup −1} Pa and ambient pressure. Therefore, a two-stage liquid ring pump in combination with a booster vapor diffusion pump will be applied. In this paper, a close-to-final design of the pumps is being described. Finite element (FEM) simulation results of components where high mechanical stresses due to thermal gradients are expected are presented. Furthermore, the final design of the control and data acquisition system is shown and explained.
Exchangers man the pumps: Functional interplay between proton pumps and proton-coupled Ca(2+) exchangers

Science.gov (United States)

Tonoplast-localised proton-coupled Ca(2+) transporters encoded by cation/H(+) exchanger (CAX) genes play a critical role in sequestering Ca(2+) into the vacuole. These transporters may function in coordination with Ca(2+) release channels, to shape stimulus-induced cytosolic Ca(2+) elevations. Recen...
Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits

Directory of Open Access Journals (Sweden)

Gwee KA

2018-02-01

Full Text Available Kok Ann Gwee,1 Vernadine Goh,2 Graca Lima,3 Sajita Setia4 1Stomach, Liver, and Bowel Centre, Gleneagles Hospital, 2Department of Pharmacy, National University of Singapore, Singapore; 3Global Medical Affairs, Asia-Pacific Region, Pfizer, Hong Kong; 4Medical Affairs, Pfizer, Singapore Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs are often coadministered with proton-pump inhibitors (PPIs to reduce NSAID-induced gastrointestinal (GI adverse events. This coadministration is generally regarded as safe, and is included in many of the guidelines on NSAID prescription. However, recent evidence indicates that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs. This review discusses the GI effects and complications of NSAIDs and how PPIs may potentiate these effects, options for prevention of GI side effects, and appropriate use of PPIs in combination with NSAIDs. Keywords: PPIs, COX2 inhibitors, NSAIDs, enteropathy, gastrointestinal
Mechanisms of generation of local ΔpH in mitochondria and bacteria.

Science.gov (United States)

Medvedev, E S; Stuchebrukhov, A A

2014-05-01

The concepts of global and local coupling between proton generators, the enzymes of the respiratory chain, and the consumer, the ATP synthase, coexist in the theory of oxidative phosphorylation. Global coupling is trivial proton transport via the aqueous medium, whereas local coupling implies that the protons pumped are consumed before they escape to the bulk phase. In this work, the conditions for the occurrence of local coupling are explored. It is supposed that the membrane retains protons near its surface and that the proton current generated by the proton pumps rapidly decreases with increasing proton motive force (pmf). It is shown that the competition between the processes of proton translocation across the membrane and their dissipation from the surface to the bulk can result in transient generation of a local ΔpH in reply to a sharp change in pmf; the appearance of local ΔpH, in turn, leads to rapid recovery of the pmf, and hence, it provides for stabilization of the potential at the membrane. Two mechanisms of such kind are discussed: 1) pH changes in the surface area due to proton pumping develop faster than those due to proton escape to the bulk; 2) the former does not take place, but the protons leaving the surface do not equilibrate with the bulk immediately; rather, they give rise to a non-equilibrium concentration near the surface and, as a result, to a back proton flow to the surface. The first mechanism is more efficient, but it does not occur in mitochondria and neutrophilic bacteria, whereas the second can produce ΔpH on the order of unity. In the absence of proton retardation at the surface, local ΔpH does not arise, whereas the formation of global ΔpH is possible only at buffer concentration of less than 10 mM. The role of the mechanisms proposed in transitions between States 3 and 4 of the respiratory chain is discussed. The main conclusion is that surface protons, under conditions where they play a role, support stabilization of the
Materials for water pump mechanical seals

International Nuclear Information System (INIS)

Brousse, P.

1992-01-01

In view of the continually increasing power ratings of conventional and nuclear power plants and the related reliability and safety problems, plant builders have had to develop seal systems compatible with current water pump performances. In 1970, EDF/R and DD was already concerned by this problem. It soon became obvious that the nature of the materials used for the friction surfaces was decisive for seal durability. Exceptional loads (transients, high vibration levels, etc...) hasten aging. To begin with, friction surfaces consisted of a hard material (tungsten carbide) mated with a soft material (carbon). Resistance was unpredictable and not compatible with industrial requirements. Tests performed on the EDF/R and DD test benches evidenced the same types of degradation. The mechanical seal manufacturers then began to use ceramic materials (silicon carbide), which raised high expectations. Unfortunately, these were recent materials and their manufacturing process was not thoroughly understood. Hopes were soon dashed in many applications, including that of mechanical seals. Fluctuating results were obtained over the next few years. The raw material suppliers made progress, especially with regard to reducing fragility. On a parallel, the mechanical seal manufacturers initiated comparative tests on the friction resistance of materials. It has also been established that ceramics have to be stringently supervised at all levels: part design, inspection, assembly, use. EDF has much insisted that mechanical seal suppliers guarantee the constant quality of their products. EDF/R and DD has systematically tested new sensitive devices, under normal and exceptional conditions, prior to their installation at the plants. At the present time, the silicon carbides proposed by the mechanical seal suppliers are entirely satisfactory. The carbon mating surface was far less problematic. The required reliability was obtained by replacing resin binder carbons by the more resistant
Chimeric Proton-Pumping Rhodopsins Containing the Cytoplasmic Loop of Bovine Rhodopsin

Science.gov (United States)

Sasaki, Kengo; Yamashita, Takahiro; Yoshida, Kazuho; Inoue, Keiichi; Shichida, Yoshinori; Kandori, Hideki

2014-01-01

G-protein-coupled receptors (GPCRs) transmit stimuli to intracellular signaling systems. Rhodopsin (Rh), which is a prototypical GPCR, possesses an 11-cis retinal. Photoisomerization of 11-cis to all-trans leads to structural changes in the protein of cytoplasmic loops, activating G-protein. Microbial rhodopsins are similar heptahelical membrane proteins that function as bacterial sensors, light-driven ion-pumps, or light-gated channels. They possess an all-trans retinal, and photoisomerization to 13-cis triggers structural changes in protein. Despite these similarities, there is no sequence homology between visual and microbial rhodopsins, and microbial rhodopsins do not activate G-proteins. In this study, new chimeric proton-pumping rhodopsins, proteorhodopsin (PR) and Gloeobacter rhodopsin (GR) were designed by replacing cytoplasmic loops with bovine Rh loops. Although G-protein was not activated by the PR chimeras, all 12 GR chimeras activated G-protein. The GR chimera containing the second cytoplasmic loop of bovine Rh did not activate G-protein. However, the chimera with a second and third double-loop further enhanced G-protein activation. Introduction of an E132Q mutation slowed the photocycle 30-fold and enhanced activation. The highest catalytic activity of the GR chimera was still 3,200 times lower than bovine Rh but only 64 times lower than amphioxus Go-rhodopsin. This GR chimera showed a strong absorption change of the amide-I band on a light-minus-dark difference FTIR spectrum which could represent a larger helical opening, important for G-protein activation. The light-dependent catalytic activity of this GR chimera makes it a potential optogenetic tool for enzymatic activation by light. PMID:24621599
Tests of dry mechanical forepumps for use in the ITER vacuum pumping system

International Nuclear Information System (INIS)

Kirchhof, U.; Kammerer, B.; Perinic, D.

1995-04-01

This report is a description of the design and construction of FORTE (Forepumps Test Facility) which has been built in order to enable testing of the pumping speeds of prototypical mechanical forepumps connected in series, as proposed for the ITER forepump system. Three NORMETEX pumps (1300, 600, 60 m 3 /h) and one METAL BELLOWS pump (6m 3 /h) have been integrated into the test bench. Measurements of the pumping characteristics were performed, both with the single pumps and with trains of series connected pumps, using the gases N 2 , H 2 , D 2 , He as well as ITER typical gas mixture. The results of the tests are presented. (orig.)
Research on performance of upstream pumping mechanical seal with different deep spiral groove

International Nuclear Information System (INIS)

Wang, Q; Chen, H L; Liu, T; Liu, Y H; Liu, Z B; Liu, D H

2012-01-01

As one new type of mechanical seal, Upstream Pumping Mechanical Seal has been widely used in fluid machinery. In this paper, structure of spiral groove is innovatively optimized to improve performance of Upstream Pumping Mechanical Seal with Spiral Groove: keeping the dam zone and the weir zone not changed, changing the bottom shape of spiral groove only, substituting different deep spiral groove for equal deep spiral groove. The simulation on Upstream Pumping Mechanical Seal with different deep spiral grooves is done using FVM method. According to calculation, the performances of opening force and pressure distribution on seals face are obtained. Five types of spiral grooves are analyzed, namely equal deep spiral groove, circumferential convergent ladder-like different deep spiral groove, circumferential divergent ladder-like different deep spiral groove, radial convergent ladder-like different deep spiral groove and radial divergent ladder-like different deep spiral groove. This paper works on twenty-five working conditions. The results indicate the performances of circumferential divergent 2-ladder different deep spiral groove are better than the others, with more opening force and better stabilization, while with the same leakage. The outcome provides theoretical support for application of Upstream Pumping Mechanical Seal with circumferential convergent ladder-like different deep spiral groove.
Research on performance of upstream pumping mechanical seal with different deep spiral groove

Science.gov (United States)

Wang, Q.; Chen, H. L.; Liu, T.; Liu, Y. H.; Liu, Z. B.; Liu, D. H.

2012-11-01

As one new type of mechanical seal, Upstream Pumping Mechanical Seal has been widely used in fluid machinery. In this paper, structure of spiral groove is innovatively optimized to improve performance of Upstream Pumping Mechanical Seal with Spiral Groove: keeping the dam zone and the weir zone not changed, changing the bottom shape of spiral groove only, substituting different deep spiral groove for equal deep spiral groove. The simulation on Upstream Pumping Mechanical Seal with different deep spiral grooves is done using FVM method. According to calculation, the performances of opening force and pressure distribution on seals face are obtained. Five types of spiral grooves are analyzed, namely equal deep spiral groove, circumferential convergent ladder-like different deep spiral groove, circumferential divergent ladder-like different deep spiral groove, radial convergent ladder-like different deep spiral groove and radial divergent ladder-like different deep spiral groove. This paper works on twenty-five working conditions. The results indicate the performances of circumferential divergent 2-ladder different deep spiral groove are better than the others, with more opening force and better stabilization, while with the same leakage. The outcome provides theoretical support for application of Upstream Pumping Mechanical Seal with circumferential convergent ladder-like different deep spiral groove.
Research on energy conversion mechanism of a screw centrifugal pump under the water

International Nuclear Information System (INIS)

Quan, H; Li, R N; Han, W; Cheng, X R; Shen, Z J; Su, Q M

2013-01-01

In order to research screw centrifugal pump impeller power capability and energy conversion mechanism, we used Navier-Stokes equation and standard k-ε equation turbulence model on the basis of the Euler equations to carry out screw centrifugal pump internal flow numerical simulation. This was explored by simulating specific design conditions; the medium is water, variation of speed and pressure of flow filed under the action of the impeller, and the screw centrifugal impeller shroud line and wheel line segment take monitoring sites. The monitoring points are between dynamic head and static head change to analyze the energy conversion capability along the impeller corners of screw centrifugal pump. The results show that the energy of fluid of the screw centrifugal pump is provided by spiral segment, the spiral segment in front of the impeller has played a multi-level role, it has significant reference value to research the energy conversion mechanism of screw centrifugal pump under solid-liquid two phase
A comparison of the heat and mechanical energy of a heat-pump wind turbine system

Energy Technology Data Exchange (ETDEWEB)

Aybek, A.; Arslan, S.; Yildiz, E.; Atik, K. [University of Kahramanmaras (Turkey). Dept. of Agricultural Machinery

2000-07-01

While a variety of applications of wind energy have been studied in Turkey, no significant efforts have been made to utilize heat pumps for heat generation. The use of heat pumps in wind energy systems is worth considering because of the high efficiency of heat production. In this study, a directly coupled wind turbine-heat pump system was designed, constructed, and tested. Measurements determined the mechanical energy of the rotors of the wind turbine and the heat energy generated by the heat pump driven by the rotor shaft. Based on the comparisons between the power generated by the heat pump and the power of the Savonius rotors, it was found that the heat energy gained by the heat pump was four times greater than the mechanical energy obtained from the turbine. It was suggested that heat pumps could be efficiently used in wind energy systems. (Author)
Mechanisms behind the generation of protonated ions for polyaromatic hydrocarbons by atmospheric pressure photoionization.

Science.gov (United States)

Ahmed, Arif; Choi, Cheol Ho; Choi, Myoung Choul; Kim, Sunghwan

2012-01-17

In this study, the mechanism behind the generation of protonated polyaromatic hydrocarbon (PAH) ions without heteroatoms by atmospheric pressure photoionization (APPI) is investigated. Comparing data obtained by APPI of anthracene dissolved either in toluene or perdeuterated toluene suggests that toluene acts as a source of protons and that breakage of C-H bonds in the toluene molecule is important for the overall protonation reaction. Our data describing an Arrhenius-type temperature-dependent relationship between the signal intensities of molecular and protonated ions suggest a mechanistic relation between the generated molecular and protonated ions. The APPI protonation mechanism that best explains the observed phenomena is composed of two reactions: electron transfer followed by hydrogen transfer. This two-step mechanism for APPI was originally suggested by Syage (Syage, J. A. J. Am. Soc. Mass Spectrom. 2004, 15 , 1521-1533). Further quantum mechanical study shows that an energetically favorable ion-molecular complex can be generated as a result of electron transfer from toluene to PAH, which subsequently facilitates hydrogen transfer. This suggests that both electron transfer and hydrogen transfer can occur as a "concerted" reaction through the ion-molecular complex precursor state, which is consistent with experimental results. To our best knowledge, this is the first time that the dynamic nature of the APPI process is clearly revealed by combined experimental and quantum mechanical studies.

-pumping pyrophosphatase in pepper plants

KAUST Repository

Vigani, Gianpiero; Rolli, Eleonora; Marasco, Ramona; Dell'Orto, Marta; Michoud, Gregoire; Soussi, Asma; Raddadi, Noura; Borin, Sara; Sorlini, Claudia; Zocchi, Graziano; Daffonchio, Daniele

2018-01-01

It has been previously shown that the transgenic overexpression of the plant root vacuolar proton pumps H+ -ATPase (V-ATPase) and H+ -PPase (V-PPase) confer tolerance to drought. Since plant-root endophytic bacteria can also promote drought tolerance, we hypothesize that such promotion can be associated to the enhancement of the host vacuolar proton pumps expression and activity. To test this hypothesis, we selected two endophytic bacteria endowed with an array of in vitro plant growth promoting traits. Their genome sequences confirmed the presence of traits previously shown to confer drought resistance to plants, such as the synthesis of nitric oxide and of organic volatile organic compounds. We used the two strains on pepper (Capsicuum annuum L.) because of its high sensitivity to drought. Under drought conditions, both strains stimulated a larger root system and enhanced the leaves' photosynthetic activity. By testing the expression and activity of the vacuolar proton pumps, H+ -ATPase (V-ATPase) and H+ -PPase (V-PPase), we found that bacterial colonization enhanced V-PPase only. We conclude that the enhanced expression and activity of V-PPase can be favoured by the colonization of drought-tolerance-inducing bacterial endophytes. This article is protected by copyright. All rights reserved.
-pumping pyrophosphatase in pepper plants

KAUST Repository

Vigani, Gianpiero

2018-05-22

It has been previously shown that the transgenic overexpression of the plant root vacuolar proton pumps H+ -ATPase (V-ATPase) and H+ -PPase (V-PPase) confer tolerance to drought. Since plant-root endophytic bacteria can also promote drought tolerance, we hypothesize that such promotion can be associated to the enhancement of the host vacuolar proton pumps expression and activity. To test this hypothesis, we selected two endophytic bacteria endowed with an array of in vitro plant growth promoting traits. Their genome sequences confirmed the presence of traits previously shown to confer drought resistance to plants, such as the synthesis of nitric oxide and of organic volatile organic compounds. We used the two strains on pepper (Capsicuum annuum L.) because of its high sensitivity to drought. Under drought conditions, both strains stimulated a larger root system and enhanced the leaves\\' photosynthetic activity. By testing the expression and activity of the vacuolar proton pumps, H+ -ATPase (V-ATPase) and H+ -PPase (V-PPase), we found that bacterial colonization enhanced V-PPase only. We conclude that the enhanced expression and activity of V-PPase can be favoured by the colonization of drought-tolerance-inducing bacterial endophytes. This article is protected by copyright. All rights reserved.
Acidic digestion in a teleost: postprandial and circadian pattern of gastric pH, pepsin activity, and pepsinogen and proton pump mRNAs expression.

Science.gov (United States)

Yúfera, Manuel; Moyano, Francisco J; Astola, Antonio; Pousão-Ferreira, Pedro; Martínez-Rodríguez, Gonzalo

2012-01-01

Two different modes for regulation of stomach acid secretion have been described in vertebrates. Some species exhibit a continuous acid secretion maintaining a low gastric pH during fasting. Others, as some teleosts, maintain a neutral gastric pH during fasting while the hydrochloric acid is released only after the ingestion of a meal. Those different patterns seem to be closely related to specific feeding habits. However, our recent observations suggest that this acidification pattern could be modified by changes in daily feeding frequency and time schedule. The aim of this study was to advance in understanding the regulation mechanisms of stomach digestion and pattern of acid secretion in teleost fish. We have examined the postprandial pattern of gastric pH, pepsin activity, and mRNA expression for pepsinogen and proton pump in white seabream juveniles maintained under a light/dark 12/12 hours cycle and receiving only one morning meal. The pepsin activity was analyzed according to the standard protocol buffering at pH 2 and using the actual pH measured in the stomach. The results show how the enzyme precursor is permanently available while the hydrochloric acid, which activates the zymogen fraction, is secreted just after the ingestion of food. Results also reveal that analytical protocol at pH 2 notably overestimates true pepsin activity in fish stomach. The expression of the mRNA encoding pepsinogen and proton pump exhibited almost parallel patterns, with notable increases during the darkness period and sharp decreases just before the morning meal. These results indicate that white seabream uses the resting hours for recovering the mRNA stock that will be quickly used during the feeding process. Our data clearly shows that both daily illumination pattern and feeding time are involved at different level in the regulation of the secretion of digestive juices.
Acidic digestion in a teleost: postprandial and circadian pattern of gastric pH, pepsin activity, and pepsinogen and proton pump mRNAs expression.

Directory of Open Access Journals (Sweden)

Manuel Yúfera

Full Text Available Two different modes for regulation of stomach acid secretion have been described in vertebrates. Some species exhibit a continuous acid secretion maintaining a low gastric pH during fasting. Others, as some teleosts, maintain a neutral gastric pH during fasting while the hydrochloric acid is released only after the ingestion of a meal. Those different patterns seem to be closely related to specific feeding habits. However, our recent observations suggest that this acidification pattern could be modified by changes in daily feeding frequency and time schedule. The aim of this study was to advance in understanding the regulation mechanisms of stomach digestion and pattern of acid secretion in teleost fish. We have examined the postprandial pattern of gastric pH, pepsin activity, and mRNA expression for pepsinogen and proton pump in white seabream juveniles maintained under a light/dark 12/12 hours cycle and receiving only one morning meal. The pepsin activity was analyzed according to the standard protocol buffering at pH 2 and using the actual pH measured in the stomach. The results show how the enzyme precursor is permanently available while the hydrochloric acid, which activates the zymogen fraction, is secreted just after the ingestion of food. Results also reveal that analytical protocol at pH 2 notably overestimates true pepsin activity in fish stomach. The expression of the mRNA encoding pepsinogen and proton pump exhibited almost parallel patterns, with notable increases during the darkness period and sharp decreases just before the morning meal. These results indicate that white seabream uses the resting hours for recovering the mRNA stock that will be quickly used during the feeding process. Our data clearly shows that both daily illumination pattern and feeding time are involved at different level in the regulation of the secretion of digestive juices.
Incremental cost effectiveness of proton pump inhibitors for the prevention of non-steroidal anti-inflammatory drug ulcers : a pharmacoeconomic analysis linked to a case-control study

NARCIS (Netherlands)

Vonkeman, H.E.; Braakman-Jansen, L.M.A.; Klok, R.M.; Postma, M.J.; Brouwers, J.R.B.J.; van de Laar, M.A.F.J.

2008-01-01

Introduction We estimated the cost effectiveness of concomitant proton pump inhibitors (PPIs) in relation to the occurrence of non-steroidal anti-inflammatory drug (NSAID) ulcer complications. Methods This study was linked to a nested case-control study. Patients with NSAID ulcer complications were
Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use.

Science.gov (United States)

Kinoshita, Yoshikazu; Ishimura, Norihisa; Ishihara, Shunji

2018-04-30

Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed. PPIs tend to be given for conditions in which the necessity of the drug has not been clarified, thus otherwise rare adverse effects are presented as clinically relevant. Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit and to continue to investigate their adverse effects with high quality prospective studies.
Association of Proton Pump Inhibitor (PPI Use with Energy Intake, Physical Activity, and Weight Gain

Directory of Open Access Journals (Sweden)

Jennifer L. Czwornog

2015-10-01

Full Text Available Studies suggest proton pump inhibitor (PPI use impacts body weight regulation, though the effect of PPIs on energy intake, energy extraction, and energy expenditure is unknown. We used data on 3073 eligible adults from the National Health and Nutrition Examination Survey (NHANES. Medication use, energy intake, diet composition, and physical activity were extracted from NHANES. Multivariate regression models included confounding variables. Daily energy intake was similar between PPI users and non-users (p = 0.41. Diet composition was similar between the two groups, except that PPI users consumed a slightly greater proportion of calories from fat (34.5% vs. 33.2%; p = 0.02. PPI users rated themselves as being as physically active as their age/gender-matched peers and reported similar frequencies of walking or biking. However, PPI users were less likely to have participated in muscle-strengthening activities (OR: 0.53; 95% CI: 0.30–0.95. PPI users reported similar sedentary behaviors to non-users. Male PPI users had an increase in weight (of 1.52 ± 0.59 kg; p = 0.021 over the previous year compared to non-users, while female PPI users had a non-significant increase in weight. The potential mechanisms for PPI-associated weight gain are unclear as we did not find evidence for significant differences in energy intake or markers of energy expenditure.
Proton dynamics in cancer.

Science.gov (United States)

Huber, Veronica; De Milito, Angelo; Harguindey, Salvador; Reshkin, Stephan J; Wahl, Miriam L; Rauch, Cyril; Chiesi, Antonio; Pouysségur, Jacques; Gatenby, Robert A; Rivoltini, Licia; Fais, Stefano

2010-06-15

Cancer remains a leading cause of death in the world today. Despite decades of research to identify novel therapeutic approaches, durable regressions of metastatic disease are still scanty and survival benefits often negligible. While the current strategy is mostly converging on target-therapies aimed at selectively affecting altered molecular pathways in tumor cells, evidences are in parallel pointing to cell metabolism as a potential Achilles' heel of cancer, to be disrupted for achieving therapeutic benefit. Critical differences in the metabolism of tumor versus normal cells, which include abnormal glycolysis, high lactic acid production, protons accumulation and reversed intra-extracellular pH gradients, make tumor site a hostile microenvironment where only cancer cells can proliferate and survive. Inhibiting these pathways by blocking proton pumps and transporters may deprive cancer cells of a key mechanism of detoxification and thus represent a novel strategy for a pleiotropic and multifaceted suppression of cancer cell growth.Research groups scattered all over the world have recently started to investigate various aspects of proton dynamics in cancer cells with quite encouraging preliminary results. The intent of unifying investigators involved in this research line led to the formation of the "International Society for Proton Dynamics in Cancer" (ISPDC) in January 2010. This is the manifesto of the newly formed society where both basic and clinical investigators are called to foster translational research and stimulate interdisciplinary collaboration for the development of more specific and less toxic therapeutic strategies based on proton dynamics in tumor cell biology.
Use of proton pump inhibitors is associated with fractures in young adults: a population-based study.

Science.gov (United States)

Freedberg, D E; Haynes, K; Denburg, M R; Zemel, B S; Leonard, M B; Abrams, J A; Yang, Y-X

2015-10-01

Proton pump inhibitors (PPIs) are associated with risk for fracture in osteoporotic adults. In this population-based study, we found a significant association between PPIs and fracture in young adults, with evidence of a dose-response effect. Young adults who use PPIs should be cautioned regarding risk for fracture. Proton pump inhibitors (PPIs) are associated with fracture in adults with osteoporosis. Because PPI therapy may interfere with bone accrual and attainment of peak bone mineral density, we studied the association between use of PPIs and fracture in children and young adults. We conducted a population-based, case-control study nested within records from general medical practices from 1994 to 2013. Participants were 4-29 years old with ≥ 1 year of follow-up who lacked chronic conditions associated with use of long-term acid suppression. Cases of fracture were defined as the first incident fracture at any site. Using incidence density sampling, cases were matched with up to five controls by age, sex, medical practice, and start of follow-up. PPI exposure was defined as 180 or more cumulative doses of PPIs. Conditional logistic regression was used to estimate the odds ratio and confidence interval for use of PPIs and fracture. We identified 124,799 cases and 605,643 controls. The adjusted odds ratio for the risk of fracture associated with PPI exposure was 1.13 (95% CI 0.92 to 1.39) among children aged young adults aged 18-29 years old. In young adults but not children, we observed a dose-response effect with increased total exposure to PPIs (p for trend young adults, but overall evidence did not support a PPI-fracture relationship in children. Young adults who use PPIs should be cautioned regarding potentially increased risk for fracture, even if they lack traditional fracture risk factors.
The AcrB efflux pump: conformational cycling and peristalsis lead to multidrug resistance.

Science.gov (United States)

Seeger, Markus A; Diederichs, Kay; Eicher, Thomas; Brandstätter, Lorenz; Schiefner, André; Verrey, François; Pos, Klaas M

2008-09-01

Antimicrobial resistance of human pathogenic bacteria is an emerging problem for global public health. This resistance is often associated with the overproduction of membrane transport proteins that are capable to pump chemotherapeutics, antibiotics, detergents, dyes and organic solvents out of the cell. In Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, tripartite multidrug efflux systems extrude a large variety of cytotoxic substances from the cell membrane directly into the medium bypassing the periplasm and the outer membrane. In E. coli, the tripartite efflux system AcrA/AcrB/TolC is the pump in charge of the efflux of multiple antibiotics, dyes, bile salts and detergents. The trimeric outer membrane factor (OMF) TolC forms a beta-barrel pore in the outer membrane and exhibits a long periplasmic alpha-helical conduit. The periplasmic membrane fusion protein (MFP) AcrA serves as a linker between TolC and the trimeric resistance nodulation cell division (RND) pump AcrB, located in the inner membrane acting as a proton/drug antiporter. The newly elucidated asymmetric structure of trimeric AcrB reveals three different monomer conformations representing consecutive states in a transport cycle. The monomers show tunnels with occlusions at different sites leading from the lateral side through the periplasmic porter (pore) domains towards the funnel of the trimer and TolC. The structural changes create a hydrophobic pocket in one monomer, which is not present in the other two monomers. Minocyclin and doxorubicin, both AcrB substrates, specifically bind to this pocket substantiating its role as drug binding pocket. The energy transduction from the proton motive force into drug efflux includes proton binding in (and release from) the transmembrane part. The conformational changes observed within a triad of essential, titratable residues (Asp407/Asp408/Lys940) residing in the hydrophobic transmembrane domain appear to be transduced by
A plant-like proton-pump partnership in the malaria parasite

International Nuclear Information System (INIS)

Allen, R.J.W.; Saliba, K.J.; Zissis, S.; Kirk, K.

2001-01-01

Full text: The 'intraerythrocytic' form of the human malaria parasite. Plasmodium falciparum contains an acidic 'digestive vacuole' which is believed to be the main site of haemoglobin degradation, and the major site of action of many antimalarial drugs. The mechanism/s by which this organelle is acidified have not been investigated. In plant cells, the internal acidic vacuole has on its membrane two types of H + -pumps which contribute to the generation of an acidic pH: a vacuolar-type H + -ATPase (V-H + -ATPase) and a vacuolar H + -pyrophosphatase (V-H + -PPase). The presence of a V-H + -ATPase on the digestive vacuole membrane of P. falciparum has been demonstrated by immuno-electron microscopy (J. Biol. Chem. (2000) 275: 34353-34358) but its functional activity on this organelle has not been demonstrated. Two V-H + -PPase genes have been shown to be expressed in the intraerythrocytic stage of the P. falciparum parasite (Mol. Biochem. Parasitol. (2001) 114: 183-195); however, immunological methods failed to detect either on the parasite digestive vacuole. In this study we use a combination of NMR spectroscopy and fluorescence techniques to show that (i) P. falciparum contains low levels of pyrophosphate, and (ii) that both ATP and pyrophosphate are able to energise the acidification of the parasite's digestive vacuole. We propose that, like many plant cells the digestive vacuole of P. falciparum parasites has, on its membrane, a V-H + -PPase as well as a V-H + -ATPaSe, and that both pumps contribute to the pH regulation of this organelle
Experimental evaluation of mechanical heart support system based on viscous friction disc pump

Directory of Open Access Journals (Sweden)

A. M. Chernyavskiy

2017-01-01

Full Text Available Aim. Experimental evaluation of the viscous friction disk pump efficiency, studying the relationship between inter-disk clearance and sizes of input and output ports and pump performance parameters.Materials and methods. To assess the characteristics and to optimize the disk friction pump design the pump model and experimental stand were created. Pump dimensions were set on the basis of medical and biological requirements for mechanical heart support systems and with due consideration of the experimental studies of our colleagues from Pennsylvania. Flow volume of the working fluid was measured by float rotameter Krohne VA-40 with measurement error of not more than 1%. The pressure values in the hydrodynamic circuit were measured using a monitor manufactured by Biosoft-M. Expansion device allowed changing the flow resistance of the system simulating the total peripheral resistance of the circulatory system.Results. Linear direct correlation between the pump performance and the pressure drop of liquid being created at the inlet and outlet of the pump was obtained. The required flow rate (5–7 l/min and pressure (90–100 mmHg were reached when the rotor speed was in the range of 2500–3000 rev/min. It has been shown that the increase of the inlet diameter to 15 mm has not resulted in a significant increase in the pump performance, and that the highest efficiency values can be obtained for the magnitude of inter-disk gap of 0.4–0.5 mm.Conclusion. Designed and manufactured experimental disc pump model for pumping fluid has showed the fundamental possibility to use this model as a system for mechanical support of the heart.
Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steriodal anti-inflammatory drugs: a nested case-control study

NARCIS (Netherlands)

Vonkeman, Harald Erwin; Fernandes, Robert W.; van der Palen, Jacobus Adrianus Maria; van Roon, Eric N.; van de Laar, Mart A F J

2007-01-01

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven.
Design of a Mechanical NaK Pump for Fission Space Power Systems

Science.gov (United States)

Mireles, Omar R.; Bradley, David; Godfroy, Thomas

2010-01-01

Alkali liquid metal cooled fission reactor concepts are under development for mid-range spaceflight power requirements. One such concept utilizes a sodium-potassium eutectic (NaK) as the primary loop working fluid. Traditionally, linear induction pumps have been used to provide the required flow and head conditions for liquid metal systems but can be limited in performance. This paper details the design, build, and check-out test of a mechanical NaK pump. The pump was designed to meet reactor cooling requirements using commercially available components modified for high temperature NaK service.
Proton pump inhibitor Lansoprazole is a nuclear Liver X Receptor agonist

Science.gov (United States)

Cronican, Andrea A.; Fitz, Nicholas F.; Pham, Tam; Fogg, Allison; Kifer, Brionna; Koldamova, Radosveta; Lefterov, Iliya

2010-01-01

The liver X receptors (LXRα and LXRβ) are transcription factors that control the expression of genes primarily involved in cholesterol metabolism. In brain, in addition to normal neuronal function, cholesterol metabolism is important for APP proteolytic cleavage, secretase activities, Aβ aggregation and clearance. Particularly significant in this respect is the LXR mediated transcriptional control of APOE, which is the only proven risk factor for late onset Alzheimer’s disease. Using a transactivation reporter assay for screening pharmacologically active compounds and off patent drugs we identified the Proton Pump Inhibitor Lansoprazole as an LXR agonist. In secondary screens and counter-screening assays, it was confirmed that Lansoprazole directly activates LXR, increases the expression of LXR target genes in brain-derived human cell lines, and increases Abca1 and Apo-E protein levels in primary astrocytes derived from wild type but not LXRα/β double knockout mice. Other PPIs activate LXR as well, but the efficiency of activation depends on their structural similarities to Lansoprazole. The identification of widely used, drug with LXR agonist-like activity opens the possibility for systematic preclinical testing in at least two diseases – Alzheimer’s disease and atherosclerosis. PMID:20060385
Primary heat transport pump mechanical seal replacement strategy for Pickering B

International Nuclear Information System (INIS)

Chacinsi, V.

1995-01-01

Pickering Nuclear Generating Station is a CANDU PHWR eight unit station located on Lake Ontario. The station is divided into Pickering A (Units 1 to 4) and Pickering B (Units 5 to 8). Pickering B is the focus of this paper. Each unit is rated at 540 MWe. The Primary Heat Transport (PHT) system, which is used to cool the fuel, is divided into four quadrants. Each quadrant has four vertical Byron Jackson PHT main circulation pumps. Three pumps in each quadrant are required for normal operation, leaving one pump in each quadrant as a spare. Each Pickering PHT pump has a Byron Jackson Type SU two stage mechanical seal. The typical pressure breakdown across the seal is 8.7-4.5-1.0 MPa. Certain features of seal operation and the PHT system which influence seal replacement are discussed below. (author)
On the mechanism of irradiation effect on the function of Helix pomatia neuron Na+, K+-pump

International Nuclear Information System (INIS)

Ajrapetyan, S.N.; Egorova, E.G.; Sagiyan, A.A.; Dadalyan, S.S.; Dvoretskij, A.I.; Sulejmonyan, M.A.

1987-01-01

Mechanism of irradiation effect on passive permeability, Na + /Ca 2+ exchange, Na + , K + -pump function intensity, the number of membrane functionally active pump units (Na + , K + -ATP-ase molecules) was determined using Helix pomatia and nervous ganglions isolated from them and irradiated by 5.16 Kl/kg dose. The data obtained show that ionizing radiation leads to obvious destructions in the mechanisms of neuron Na + , K + -pump functioning
An intelligent displacement pumping film system: A new concept for enhancing heavy metal ion removal efficiency from liquid waste

International Nuclear Information System (INIS)

Wang, Zhongde; Feng, Yanting; Hao, Xiaogang; Huang, Wei; Guan, Guoqing; Abudula, Abuliti

2014-01-01

Highlights: • A new concept for design of an intelligent displacement pumping film was proposed. • As-prepared ESIX hybrid film system showed excellent Ni 2+ uptake/exclude rate. • Piston-like proton pumping effect existed in the prepared ESIX hybrid film. • The mechanism of the ion pumping effect was proved by XPS analysis. - Abstract: A concept of electrochemically switched ion exchange (ESIX) hybrid film system with piston-like proton pumping effect for the removal of heavy metal ions was proposed. Based on this concept, a novel ESIX hybrid film composed of layered alpha zirconium phosphate (α-Zr(HPO 4 ) 2 ; α-ZrP) nanosheets intercalated with a potential-responsive conducting polyaniline (PANI) was developed for the removal of Ni 2+ ions from wastewater. It is expected that the space between α-ZrP nanosheets acts as the reservoir for the functional ions while the intercalated PANI works as the potential-sensitive function element for piston-like proton pumping in such ESIX hybrid films. The prepared ESIX hybrid film showed an excellent property of rapid removal of Ni 2+ ions from wastewater with a high selectivity. The used film was simply regenerated by only altering the applied potential. The ion pumping effect for the ESIX of Ni 2+ ions using this kind of film was proved via XPS analysis. The proposed ESIX hybrid film should have high potential for the removal of Ni 2+ ions and/or other heavy metal ions from wastewater in various industrial processes
Exchangers man the pumps: Functional interplay between proton pumps and proton-coupled Ca2+ exchangers

OpenAIRE

Barkla, Bronwyn J; Hirschi, Kendal D; Pittman, Jon K

2008-01-01

Tonoplast-localised proton-coupled Ca2+ transporters encoded by cation/H+ exchanger (CAX) genes play a critical role in sequestering Ca2+ into the vacuole. These transporters may function in coordination with Ca2+ release channels, to shape stimulus-induced cytosolic Ca2+ elevations. Recent analysis of Arabidopsis CAX knockout mutants, particularly cax1 and cax3, identified a variety of phenotypes including sensitivity to abiotic stresses, which indicated that these transporters might play a ...
Comparison of vonoprazan and proton pump inhibitors for eradication of Helicobacter pylori

Directory of Open Access Journals (Sweden)

Satoshi Shinozaki

2016-05-01

Full Text Available Alternative eradication therapies for Helicobacter pylori infection are needed because of an increasing failure rate over the past decade. The aim of this study was to determine if vonoprazan, a new potassium-competitive acid blocker, showed superiority to existing proton pump inhibitors for primary eradication of H. pylori in routine clinical practice. Data for 573 patients who underwent primary H. pylori eradication therapy were retrospectively reviewed. Regimens included clarithromycin 200 mg, amoxicillin 750 mg, and an acid-suppressing drug [lansoprazole 30 mg (LAC, rabeprazole 10 mg (RAC, esomeprazole 20 mg (EAC, or vonoprazan 20 mg (VAC] twice daily for 1 week. Eradication was successful in 73% (419/573 of patients using intention-to-treat (ITT analysis and 76% (419/549 of patients in per-protocol (PP analysis. The VAC group had a significantly superior eradication rate compared with the LAC and RAC groups in ITT (VAC 83%, LAC 66% and RAC 67%, p 80% eradication rate regardless of the degree of atrophy.

Effects of 12 weeks' treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes

DEFF Research Database (Denmark)

Hove, K D; Brøns, Charlotte; Færch, Kai Erik Vinther

2013-01-01

Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised double-blind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA(1c...
Study of multiple production mechanisms of neutral and charged particles in proton-proton interactions at 69GeV/c

International Nuclear Information System (INIS)

Boratav, Murat.

1976-01-01

From a sample of 30000 pictures taken in the hydrogen bubble chamber Mirabelle, with a proton beam of 69GeV/c, at Serpukhov, the multiple particle production mechanisms are studied in proton-proton collisions. The neutral pions produced are specially studied, which means that the photons coming from the disintegration of π 0 's have to be detected and measured. From these pion spectra, their multiplicity distributions and the first order moments of these distributions (particularly the Mueller correlation coefficients) data and results are compared with the predictions of theoretical models such as: 'thermodynamic' models (Feynman gas, critical fluid model, etc.) and cluster models (with a fixed size or a size depending on incoming energy). The multiple production mechanisms seem to appear through small-sized, energy-dependent clusters (about two pions per cluster at this energy) [fr
Electrolytic conductivity-the hopping mechanism of the proton and beyond

International Nuclear Information System (INIS)

Gileadi, E.; Kirowa-Eisner, E.

2006-01-01

The hopping mechanism of electrolytic conductivity is analyzed, employing mixtures of two solvents: one that sustains the hopping mechanism and the other that does not inhibit it directly, but interferes with it by diluting the solvent that sustains hopping. Measurement of the equivalent conductivity shows that the excess proton conductivities of H 3 O + and OH - increases with increasing temperature, although the number of hydrogen bonds is known to decrease. In mixtures of acetonitrile with water, proton hopping does not start until a threshold concentration of about 20 vol.% water has been reached, while no such threshold concentration is observed upon addition of methanol to acetonitrile. It is concluded that in the former the proton is transferred to a cluster of water molecules, which can be formed only if there is enough water in the solvent mixture. This observation leads to the concept of mono-water, which is the state of water molecules when they constitute a small minority in the solvent mixtures, as opposed to bulk water, which consists of clusters of variable sizes. Systems in which a hopping mechanism of heavy ions has been observed include Br - /Br 2 and I - /I 2 . In these cases the triple ions Br 3 - and I 3 - , respectively are formed, and serve as the mediators for the transfer of the simple halogen ion. A very large increase of conductivity was observed upon solidification of the Br - /Br 3 - system, probably caused by favorable linear alignment of ions in the solid. The conductivity of acidified methanol decreases upon addition of water, because the affinity of the proton to water is higher than to methanol, thus water can act as a scavenger for protons. This behavior exemplifies a general observation, namely that conductivity by hopping can only occur when the Gibbs energy of the system does not change significantly following ion transfer; otherwise the ions would be trapped in the more stable state, hindering further propagation by hopping
A plant-like proton-pump partnership in the malaria parasite

Energy Technology Data Exchange (ETDEWEB)

Allen, R J.W.; Saliba, K J; Zissis, S; Kirk, K [Australian National University, ACT (Australia)

2001-07-01

Full text: The 'intraerythrocytic' form of the human malaria parasite. Plasmodium falciparum contains an acidic 'digestive vacuole' which is believed to be the main site of haemoglobin degradation, and the major site of action of many antimalarial drugs. The mechanism/s by which this organelle is acidified have not been investigated. In plant cells, the internal acidic vacuole has on its membrane two types of H{sup +}-pumps which contribute to the generation of an acidic pH: a vacuolar-type H{sup +}-ATPase (V-H{sup +}-ATPase) and a vacuolar H{sup +}-pyrophosphatase (V-H{sup +}-PPase). The presence of a V-H{sup +}-ATPase on the digestive vacuole membrane of P. falciparum has been demonstrated by immuno-electron microscopy (J. Biol. Chem. (2000) 275: 34353-34358) but its functional activity on this organelle has not been demonstrated. Two V-H{sup +}-PPase genes have been shown to be expressed in the intraerythrocytic stage of the P. falciparum parasite (Mol. Biochem. Parasitol. (2001) 114: 183-195); however, immunological methods failed to detect either on the parasite digestive vacuole. In this study we use a combination of NMR spectroscopy and fluorescence techniques to show that (i) P. falciparum contains low levels of pyrophosphate, and (ii) that both ATP and pyrophosphate are able to energise the acidification of the parasite's digestive vacuole. We propose that, like many plant cells the digestive vacuole of P. falciparum parasites has, on its membrane, a V-H{sup +}-PPase as well as a V-H{sup +}-ATPaSe, and that both pumps contribute to the pH regulation of this organelle.
Proton exchange mechanism of synthesizing CdS quantum dots in nafion

International Nuclear Information System (INIS)

Nandakumar, P.; Vijayan, C.; Murti, Y.V.G.S.; Dhanalakshmi, K.; Sundararajan, G.

1999-01-01

Nanocrystals of CdS are synthesized in the proton exchange membrane nafion in different sizes in the range 1.6 to 6 nm. To understand the process leading to the formation of these quantum dots, we have probed the proton exchange by ac conductance measurements in the frequency range 100 Hz to 13 MHz. Nafion shows good electrical conductivity due to proton transport probably via the Grothus mechanism. Incorporation of cadmium ions by replacement of the hydrogen ions in the sulphonic acid group resulted in a large decrease in conductance indicating the reduction of the mobile carrier density. The conductivity plots all show strong frequency dependence with higher conductance towards the higher frequencies where a near-flat frequency response is seen. After the formation of CdS clusters, there is a partial recovery of conductance corresponding to the reinstatement of the protonic carriers on the side groups. The conductivity of the nafion films embedded with the semiconductor quantum dots exhibits a size-dependence with the highest conductivity obtained for the largest clusters. These findings lend clear experimental evidence for the model of synthesis of quantum dots in nafion by the exchange mechanism. (author)
Backward emission mechanism of energetic protons studied from two-particle correlations in 800 MeV proton-nucleus collisions

International Nuclear Information System (INIS)

Miake, Yasuo

1982-07-01

The production mechanism of backward energetic protons was studied in 800 MeV proton-nucleus collision from the measurement of two-particle correlation over a wide range of kinematic regions. The backward energetic protons at 118 deg were measured in coincidence with the particles emitted in the angular range from 15 deg to 100 deg. Both in-plane and out-of-plane coincidences were measured. The backward energetic protons were detected with a delta E-E counter in a momentum region from 350 to 750 MeV/c, whereas the coincident particles were detected with a magnetic spectrometer in the momentum region from 450 to 2000 MeV/c. The reaction process of the backward protons were decomposed into six categories by the measurement of the associated particles, p or d. The momentum spectra, angular distribution and the target mass dependence of these components were studied. The component of p-p QES was well reproduced by the PW1A model, but the backward energetic protons were not from this process. The momenta of two nucleons inside the quasi-deuteron are highly correlated. The components of p-p non-QES and p-p out-of-plane are the main components of the backward energetic proton production. (Kako, I.)
Proton dynamics in cancer

Directory of Open Access Journals (Sweden)

Pouysségur Jacques

2010-06-01

Full Text Available Abstract Cancer remains a leading cause of death in the world today. Despite decades of research to identify novel therapeutic approaches, durable regressions of metastatic disease are still scanty and survival benefits often negligible. While the current strategy is mostly converging on target-therapies aimed at selectively affecting altered molecular pathways in tumor cells, evidences are in parallel pointing to cell metabolism as a potential Achilles' heel of cancer, to be disrupted for achieving therapeutic benefit. Critical differences in the metabolism of tumor versus normal cells, which include abnormal glycolysis, high lactic acid production, protons accumulation and reversed intra-extracellular pH gradients, make tumor site a hostile microenvironment where only cancer cells can proliferate and survive. Inhibiting these pathways by blocking proton pumps and transporters may deprive cancer cells of a key mechanism of detoxification and thus represent a novel strategy for a pleiotropic and multifaceted suppression of cancer cell growth. Research groups scattered all over the world have recently started to investigate various aspects of proton dynamics in cancer cells with quite encouraging preliminary results. The intent of unifying investigators involved in this research line led to the formation of the "International Society for Proton Dynamics in Cancer" (ISPDC in January 2010. This is the manifesto of the newly formed society where both basic and clinical investigators are called to foster translational research and stimulate interdisciplinary collaboration for the development of more specific and less toxic therapeutic strategies based on proton dynamics in tumor cell biology.
Proton pump inhibition and cancer therapeutics: A specific tumor targeting or it is a phenomenon secondary to a systemic buffering?

Science.gov (United States)

Spugnini, Enrico; Fais, Stefano

2017-04-01

One of the unsolved mysteries in oncology includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to the development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. In the last decades a primordial role for proton exchangers has been supported as a key tumor advantage in facing off the acidic milieu. Proton exchangers do not allow intracellular acidification through a continuous elimination of H+ either outside the cells or within the internal vacuoles. This article wants to comment a translational process through that led to the preclinical demonstration that a class of proton pump inhibitors (PPI) exploited worldwide for peptic ulcer treatment and gastroprotection are indeed powerful chemosensitizers as well. In this process we achieved the clinical proof of concept that PPI may well be included in new anti-cancer strategies with a solid background and rationale. Copyright © 2017 Elsevier Ltd. All rights reserved.
Performance of a hybrid chemical/mechanical heat pump

Science.gov (United States)

Silvestri, John J.; Scaringe, Robert P.; Grzyll, Lawrence R.

1990-01-01

The authors present the design and preliminary results of the performance of a hybrid chemical/mechanical, low-lift (20 C) heat pump. Studies have indicated that this heat pump has several advantages over the traditional single fluid vapor compression (reverse Rankine) heat pump. Included in these benefits are: 1) increased COPc due to the approximation of the cycle to the Lorenz cycle and due to the availability of the heat of solution, along with the heat of vaporization, to provide cooling; and 2) ease of variation in system cooling capacity by changing the fluid composition. The system performance is predicted for a variety of refrigerant-absorbent pairs. Cooling capacity is determined for systems operating with ammonia as the refrigerant and lithium nitrate and sodium thiocyanate as the absorbents and also with water as the refrigerant and magnesium chloride, potassium hydroxide, lithium bromide, sodium hydroxide, and sulfuric acid as the absorbents. Early indications have shown that the systems operating with water as the refrigerant operate at 2-4 times the capacity of the ammonia-refrigerant-based systems. Using existing working fluids in the proposed innovative design, a coefficient-of-performance improvement of 21 percent is possible when compared to the best vapor compression systems analyzed.
Polarized proton target-IV. Operations manual

International Nuclear Information System (INIS)

Hill, D.; Fletcher, O.; Moretti, A.; Onesto, F.

1976-01-01

Standard operating procedures are presented for the vacuum, cryogenic, and electronic systems of a polarized proton target. The systems are comprised of (1) a target cryostat; (2) a 4 He pumping system; (3) a 3 He pumping system; (4) a microwave system; (5) a magnet and power supply; (6) a computerized polarization monitor; and (7) miscellaneous auxiliary equipment
Pathogenesis of Double-Dose Proton Pump Inhibitor-Resistant Non-Erosive Reflux Disease, and Mechanism of Reflux Symptoms and Gastric Acid Secretion-Suppressive Effect in the Presence or Absence of Helicobacter pylori Infection.

Science.gov (United States)

Kawami, Noriyuki; Takenouchi, Nana; Umezawa, Mariko; Hoshino, Shintaro; Hanada, Yuriko; Hoshikawa, Yoshimasa; Sano, Hirohito; Hoshihara, Yoshio; Nomura, Tsutomu; Uchida, Eiji; Iwakiri, Katsuhiko

2017-01-01

Various mechanisms have been suggested to be responsible for contributing to the occurrence of proton pump inhibitor (PPI)-resistant non-erosive reflux disease (NERD). The aims of this study were to clarify the pathogenesis of PPI-resistant NERD. Fifty-three patients with NERD, who had persistent reflux symptoms despite taking double-dose PPI, were included in this study. After excluding eosinophilic esophagitis (EoE) and primary esophageal motility disorder, esophageal impedance-pH monitoring was carried out. In symptom index (SI)-positive patients, the mechanism of SI positivity and the percent time with intragastric pH >4 were investigated according to the presence or absence of Helicobacter pylori infection. One of the 53 patients had EoE, and 4 had primary esophageal motility disorder. Twenty-three and 2 patients were SI-positive for liquid and gas-only reflux respectively. Of 17 SI-positive, H. pylori-negative patients, 5 were SI-positive for acid reflux, whereas all of the H. pylori-positive patients were SI-positive for non-acid reflux. The percent time with intragastric pH >4 was significantly lower in the H. pylori-negative patients than in the H. pylori-positive patients. The pathogenesis of double-dose PPI-resistant NERD was identified in 57%. In some of H. pylori-negative patients, acid-related symptoms were observed. However, in H. pylori-positive patients, these symptoms were excluded by taking double-dose PPI. © 2017 S. Karger AG, Basel.
A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial

NARCIS (Netherlands)

Boeckxstaens, Guy E.; Beaumont, Hanneke; Hatlebakk, Jan G.; Silberg, Debra G.; Björck, Karin; Karlsson, Maria; Denison, Hans

2011-01-01

o evaluate the efficacy and tolerability of add-on treatment with lesogaberan (AZD3355), a novel reflux inhibitor, in patients with persistent gastro-oesophageal reflux disease (GORD) symptoms despite proton pump inhibitor (PPI) therapy. double-blind, placebo-controlled, randomised, parallel-group,
Engineering bacterial efflux pumps for solar-powered bioremediation of surface waters.

Science.gov (United States)

Kapoor, Vikram; Wendell, David

2013-05-08

Antibiotics are difficult to selectively remove from surface waters by present treatment methods. Bacterial efflux pumps have evolved the ability to discriminately expel antibiotics and other noxious agents via proton and ATP driven pathways. Here, we describe light-dependent removal of antibiotics by engineering the bacterial efflux pump AcrB into a proteovesicle system. We have created a chimeric protein with the requisite proton motive force by coupling AcrB to the light-driven proton pump Delta-rhodopsin (dR) via a glycophorin A transmembrane domain. This creates a solar powered protein material capable of selectively capturing antibiotics from bulk solutions. Using environmental water and direct sunlight, our AcrB-dR vesicles removed almost twice as much antibiotic as the treatment standard, activated carbon. Altogether, the AcrB-dR system provides an effective means of extracting antibiotics from surface waters as well as potential antibiotic recovery through vesicle solubilization.
Liquid metals pumping

International Nuclear Information System (INIS)

Le Frere, J.P.

1984-01-01

Pumps used to pump liquid metals depend on the liquid metal and on the type of application concerned. One deals more particularly with electromagnetic pumps, the main pumps used with mechanical pumps. To pump sodium in the nuclear field, these two types of pumps are used; the pumps of different circuits of Super Phenix are presented and described [fr
Inulin significantly improves serum magnesium levels in proton pump inhibitor-induced hypomagnesaemia.

Science.gov (United States)

Hess, M W; de Baaij, J H F; Broekman, M; Bisseling, T M; Haarhuis, B; Tan, A; Te Morsche, R; Hoenderop, J G J; Bindels, R J M; Drenth, J P H

2016-06-01

Proton pump inhibitors (PPI) are among the most widely prescribed drugs to treat gastric acid-related disorders. PPI-induced hypomagnesaemia, a defect in intestinal absorption of Mg(2+) , can be a severe side effect of chronic PPI use. To restore serum Mg(2+) concentrations in PPI-induced hypomagnesaemia patients by dietary supplementation with inulin fibres. Eleven patients with PPI-induced hypomagnesaemia and 10 controls were treated with inulin (20 g/day). Each trial consisted of two cycles of 14-day inulin treatment followed by a washout period of 14 days. Patients continued to use their PPI. Serum Mg(2+) levels served as the primary endpoint. Inulin significantly enhanced serum Mg(2+) levels from 0.60 to 0.68 mmol/L in PPI-induced hypomagnesaemia patients, and from 0.84 to 0.93 mmol/L in controls. As a consequence 24 h urinary Mg(2+) excretion was significantly increased in patients with PPI-induced hypomagnesaemia (0.3-2.2 mmol/day). Symptoms related to hypomagnesaemia, including muscle cramps and paraesthesia, were reduced during intervention with inulin. Inulin increases serum Mg(2+) concentrations under PPI maintenance in patients with PPI-induced hypomagnesaemia. © 2016 John Wiley & Sons Ltd.
Radiation modification and interaction mechanism of polypropylene and polyethylene by protons and electrons

International Nuclear Information System (INIS)

Wang Guanghou

1988-10-01

A systematic investigation of radiation effects on isotactic polypropylene (PP) and low-density polyethylene (PE) films by protons and electrons is reported. Electrons can make polyethylene cross-linked and polypropylene crached while protons can improve the PP mechanical properties and deteriorate polyethylene with increasing the irradiation dose. The structural analysis shows that conversion between α and β phases occurs and the crystallinity remains constant in the electron-irradiated polypropylene whereas the network structure is formed by allyl-type radicals in the e - -irradiated polyethylene. The infrared spectra indicate that conformational changes have taken place in the polypropylene under proton bombardment, such as the transition from an ordered to a disordered state in the crystalline region, the formation of double bonds as well as trans-conformations. This leads to the cross-linking between macromolecules of polypropylene at the proper irradiation doses, thus enhancing its mechanical properties. The cross-linking of polypropylene by proton bombardment observed and its properties may have some potential applications
Model for Sucker-Rod Pumping Unit Operating Modes Analysis Based on SimMechanics Library

Science.gov (United States)

Zyuzev, A. M.; Bubnov, M. V.

2018-01-01

The article provides basic information about the process of a sucker-rod pumping unit (SRPU) model developing by means of SimMechanics library in the MATLAB Simulink environment. The model is designed for the development of a pump productivity optimal management algorithms, sensorless diagnostics of the plunger pump and pumpjack, acquisition of the dynamometer card and determination of a dynamic fluid level in the well, normalization of the faulty unit operation before troubleshooting is performed by staff as well as equilibrium ratio determining by energy indicators and outputting of manual balancing recommendations to achieve optimal power consumption efficiency. Particular attention is given to the application of various blocks from SimMechanics library to take into account the pumpjack construction principal characteristic and to obtain an adequate model. The article explains in depth the developed tools features for collecting and analysis of simulated mechanism data. The conclusions were drawn about practical implementation possibility of the SRPU modelling results and areas for further development of investigation.
Proton Pump Inhibitors Intake and Iron and Vitamin B12 Status: A Prospective Comparative Study with a Follow up of 12 Months

OpenAIRE

Qorraj-Bytyqi, Hasime; Hoxha, Rexhep; Sadiku, Shemsedin; Bajraktari, Ismet H.; Sopjani, Mentor; Thaçi, Kujtim; Thaçi, Shpetim; Bahtiri, Elton

2018-01-01

BACKGROUND: Proton pump inhibitors (PPIs) represent the most widely prescribed antisecretory agents, but their prolonged use, may influence iron and vitamin B12 status, which could have important implications for clinical practice. AIM: We undertook this study aiming to investigate the association between PPIs use for 12 months and potential changes in iron and vitamin B12 status, as well as whether this potential association varies among four specific PPI drugs used in the study. MET...
Investigation of microstructure and mechanical properties of proton irradiated Zircaloy 2

Energy Technology Data Exchange (ETDEWEB)

Sarkar, Apu, E-mail: asarkar@barc.gov.in [Mechanical Metallurgy Division, Bhabha Atomic Reserch Centre, Mumbai, 400 085 (India); Kumar, Ajay [Nuclear Physics Division, Bhabha Atomic Reserch Centre, Mumbai, 400 085 (India); Mukherjee, S.; Sharma, S.K.; Dutta, D.; Pujari, P.K. [Radiochemistry Division, Bhabha Atomic Research Centre, Mumbai, 400 085 (India); Agarwal, A.; Gupta, S.K.; Singh, P. [Ion Accelerator Development Division, Bhabha Atomic Research Centre, Mumbai, 400 085 (India); Chakravartty, J.K. [Mechanical Metallurgy Division, Bhabha Atomic Reserch Centre, Mumbai, 400 085 (India)

2016-10-15

Samples of Zircaloy 2 have been irradiated with 4 MeV protons to two different doses. Microstructures of the unirradiated and irradiated samples have been characterized by Electron Back Scatter Diffraction (EBSD), X-ray diffraction line profile analysis (XRDLPA), Positron Annihilation Lifetime Spectroscopy (PALS) and Coincident Doppler Broadening (CDB) Spectroscopy. Tensile tests and micro hardness measurements have been carried out at room temperature to assess the changes in mechanical properties of Zircaloy 2 due to proton irradiation. The correlation of dislocation density, grain size and yield stress of the irradiated samples indicated that an increase in dislocation density due to irradiation is responsible for the change in mechanical behavior of irradiated Zircaloy.
Imaging an optogenetic pH sensor reveals that protons mediate lateral inhibition in the retina.

Science.gov (United States)

Wang, Tzu-Ming; Holzhausen, Lars C; Kramer, Richard H

2014-02-01

The reciprocal synapse between photoreceptors and horizontal cells underlies lateral inhibition and establishes the antagonistic center-surround receptive fields of retinal neurons to enhance visual contrast. Despite decades of study, the signal mediating the negative feedback from horizontal cells to cones has remained under debate because the small, invaginated synaptic cleft has precluded measurement. Using zebrafish retinas, we show that light elicits a change in synaptic proton concentration with the correct magnitude, kinetics and spatial dependence to account for lateral inhibition. Light, which hyperpolarizes horizontal cells, causes synaptic alkalinization, whereas activating an exogenously expressed ligand-gated Na(+) channel, which depolarizes horizontal cells, causes synaptic acidification. Whereas acidification was prevented by blocking a proton pump, re-alkalinization was prevented by blocking proton-permeant ion channels, suggesting that distinct mechanisms underlie proton efflux and influx. These findings reveal that protons mediate lateral inhibition in the retina, raising the possibility that protons are unrecognized retrograde messengers elsewhere in the nervous system.

Excited state proton transfer in strongly enhanced GFP (sGFP2).

Science.gov (United States)

van Oort, Bart; ter Veer, Mirelle J T; Groot, Marie Louise; van Stokkum, Ivo H M

2012-07-07

Proton transfer is an elementary process in biology. Green fluorescent protein (GFP) has served as an important model system to elucidate the mechanistic details of this reaction, because in GFP proton transfer can be induced by light absorption. We have used pump-dump-probe spectroscopy to study how proton transfer through the 'proton-wire' around the chromophore is affected by a combination of mutations in a modern GFP variety (sGFP2). The results indicate that in H(2)O, after absorption of a photon, a proton is transferred (A* → I*) in 5 ps, and back-transferred from a ground state intermediate (I → A) in 0.3 ns, similar to time constants found with GFPuv, although sGFP2 shows less heterogeneous proton transfer. This suggests that the mutations left the proton-transfer largely unchanged, indicating the robustness of the proton-wire. We used pump-dump-probe spectroscopy in combination with target analysis to probe suitability of the sGFP2 fluorophore for super-resolution microscopy.
Effect of a pH Gradient on the Protonation States of Cytochrome c Oxidase: A Continuum Electrostatics Study.

Science.gov (United States)

Magalhães, Pedro R; Oliveira, A Sofia F; Campos, Sara R R; Soares, Cláudio M; Baptista, António M

2017-02-27

Cytochrome c oxidase (CcO) couples the reduction of dioxygen to water with transmembrane proton pumping, which leads to the generation of an electrochemical gradient. In this study we analyze how one of the components of the electrochemical gradient, the difference in pH across the membrane, or ΔpH, influences the protonation states of residues in CcO. We modified our continuum electrostatics/Monte Carlo (CE/MC) method in order to include the ΔpH and applied it to the study of CcO, in what is, to our best knowledge, the first CE/MC study of CcO in the presence of a pH gradient. The inclusion of a transmembrane pH gradient allows for the identification of residues whose titration behavior depends on the pH on both sides of the membrane. Among the several residues with unusual titration profiles, three are well-known key residues in the proton transfer process of CcO: E286 I , Y288 I , and K362 I . All three residues have been previously identified as being critical for the catalytic or proton pumping functions of CcO. Our results suggest that when the pH gradient increases, these residues may be part of a regulatory mechanism to stem the proton flow.
Centrifugal pumps

CERN Document Server

Anderson, HH

1981-01-01

Centrifugal Pumps describes the whole range of the centrifugal pump (mixed flow and axial flow pumps are dealt with more briefly), with emphasis on the development of the boiler feed pump. Organized into 46 chapters, this book discusses the general hydrodynamic principles, performance, dimensions, type number, flow, and efficiency of centrifugal pumps. This text also explains the pumps performance; entry conditions and cavitation; speed and dimensions for a given duty; and losses. Some chapters further describe centrifugal pump mechanical design, installation, monitoring, and maintenance. The
A Rough Set Approach of Mechanical Fault Diagnosis for Five-Plunger Pump

Directory of Open Access Journals (Sweden)

Jiangping Wang

2013-01-01

Full Text Available Five-plunger pumps are widely used in oil field to recover petroleum due to their reliability and relatively low cost. Petroleum production is, to a great extent, dependent upon the running condition of the pumps. Closely monitoring the condition of the pumps and carrying out timely system diagnosis whenever a fault symptom is detected would help to reduce the production downtime and improve overall productivity. In this paper, a rough set approach of mechanical fault diagnosis is proposed to identify the five-plunger pump faults. The details of the approach, together with the basic concepts of the rough sets theory, are presented. The rough classifier is a set of decision rules derived from lower and upper approximations of decision classes. The definitions of these approximations are based on the indiscernibility relation in the set of objects. The spectrum features of vibration signals are abstracted as the attributes of the learning samples. The minimum decision rule set is used to classify technical states of the considered object. The diagnostic investigation is done on data from a five-plunger pump in outdoor conditions on a real industrial object. Results show that the approach can effectively identify the different operating states of the pump.
New insights gained on mechanisms of low-energy proton-induced SEUs by minimizing energy straggle

International Nuclear Information System (INIS)

Dodds, Nathaniel Anson; Dodd, Paul E.; Shaneyfelt, Marty R.; Sexton, Frederick W.; Martinez, Marino J.; Black, Jeffrey D.; Marshall, P. W.; Reed, R. A.; McCurdy, M. W.; Weller, R. A.; Pellish, J. A.; Rodbell, K. P.; Gordon, M. S.

2015-01-01

In this study, we present low-energy proton single-event upset (SEU) data on a 65 nm SOI SRAM whose substrate has been completely removed. Since the protons only had to penetrate a very thin buried oxide layer, these measurements were affected by far less energy loss, energy straggle, flux attrition, and angular scattering than previous datasets. The minimization of these common sources of experimental interference allows more direct interpretation of the data and deeper insight into SEU mechanisms. The results show a strong angular dependence, demonstrate that energy straggle, flux attrition, and angular scattering affect the measured SEU cross sections, and prove that proton direct ionization is the dominant mechanism for low-energy proton-induced SEUs in these circuits
The Hv1 proton channel responds to mechanical stimuli.

Science.gov (United States)

Pathak, Medha M; Tran, Truc; Hong, Liang; Joós, Béla; Morris, Catherine E; Tombola, Francesco

2016-11-01

The voltage-gated proton channel, Hv1, is expressed in tissues throughout the body and plays important roles in pH homeostasis and regulation of NADPH oxidase. Hv1 operates in membrane compartments that experience strong mechanical forces under physiological or pathological conditions. In microglia, for example, Hv1 activity is potentiated by cell swelling and causes an increase in brain damage after stroke. The channel complex consists of two proton-permeable voltage-sensing domains (VSDs) linked by a cytoplasmic coiled-coil domain. Here, we report that these VSDs directly respond to mechanical stimuli. We find that membrane stretch facilitates Hv1 channel opening by increasing the rate of activation and shifting the steady-state activation curve to less depolarized potentials. In the presence of a transmembrane pH gradient, membrane stretch alone opens the channel without the need for strong depolarizations. The effect of membrane stretch persists for several minutes after the mechanical stimulus is turned off, suggesting that the channel switches to a "facilitated" mode in which opening occurs more readily and then slowly reverts to the normal mode observed in the absence of membrane stretch. Conductance simulations with a six-state model recapitulate all the features of the channel's response to mechanical stimulation. Hv1 mechanosensitivity thus provides a mechanistic link between channel activation in microglia and brain damage after stroke. © 2016 Pathak et al.
Proton pump inhibitor failure in gastro-oesophageal reflux disease: a perspective aided by the Gartner hype cycle.

Science.gov (United States)

Heading, Robert C

2017-04-01

Some patients with gastro-oesophageal reflux disease (GORD) experience symptoms despite proton pump inhibitor (PPI) treatment. In the early years of their availability, these drugs were thought to be a highly effective treatment for GORD and realisation that symptom relief was often incomplete came as a disappointment. This review considers the evolution of thinking with the aid of the Gartner hype cycle - a graphical depiction of the process of innovation, evolution and adoption of new technologies. Acknowledging that over-simplistic concepts of GORD have been largely responsible for inflated expectations of PPI therapy is an important step forward in establishing how patients with persistent symptoms, despite PPIs, should be assessed and treated. © Royal College of Physicians 2017. All rights reserved.
Neutral Pion Production in Proton+Proton Collisions at $\\sqrt{s}=8$ TeV and Insight into Hadron Production Mechanism

CERN Document Server

Yano, Satoshi

High transverse momentum particles play an important role for investigation of Quark-Gluon Plasma (QGP) induced by nucleus-nucleus collisions. When high transverse momentum partons traverse the QGP, they lose their energy. Consequently, the yield of high transverse momentum hadron is suppressed relative to proton+proton collisions scaled by the number of binary nucleon-nucleon collisions (jet quenching). The phenomenon is expected to give us much information about properties of QGP. Thus far, almost all models consider only parton energy loss during passing through. However, the perturbative Quantum Chromo Dynamics (QCD) predicts the direct hadron production (the higher-twist effect). If hadrons produced by this mechanism exist, the hadron energy loss should be considered additionally. For checking if there is the higher-twist effect, investigation of hadron production in proton+proton collisions is suitable. The invariant differential cross sections for inclusive neutral pion at midrapidity are measured in p...
Mechanical torques generated by optically pumped atomic spin relaxation at surfaces

International Nuclear Information System (INIS)

Herman, R.M.

1982-01-01

It is argued that a valuable method of observing certain types of surface-atom interactions may lie in mechanical torques generated through the spin-orbit relaxation of valence electronic spins of optically pumped atoms at surfaces. The unusual feature of this phenomenon is that the less probable spin-orbit relaxation becomes highly visible as compared with the much more rapid paramagnetic relaxation, because of an enhancement, typically by as much as a factor 10 9 , in the torques delivered to mechanical structures, by virtue of a very large effective moment arm. Spin-orbit relaxation operates through an exchange of translational momentum which, in turn, can be identified with the delivery of a gigantic angular momentum (in units of h) relative to a distant axis about which mechanical motion is referred. The spin-orbit relaxation strongly depends upon the atomic number of the surface atoms and the strength of interaction with the optically pumped atoms. Being dominated by high-atomic-number surface atoms, spin-orbit relaxation rates may not be too strongly influenced by minor surface contamination of lighter-weight optically active atoms
Mechanical torques generated by optically pumped atomic spin relaxation at surfaces

Science.gov (United States)

Herman, R. M.

1982-03-01

It is argued that a valuable method of observing certain types of surface-atom interactions may lie in mechanical torques generated through the spin-orbit relaxation of valence electronic spins of optically pumped atoms at surfaces. The unusual feature of this phenomenon is that the less probable spin-orbit relaxation becomes highly visible as compared with the much more rapid paramagnetic relaxation, because of an enhancement, typically by as much as a factor 109, in the torques delivered to mechanical structures, by virtue of a very large effective moment arm. Spin-orbit relaxation operates through an exchange of translational momentum which, in turn, can be identified with the delivery of a gigantic angular momentum (in units of ℏ) relative to a distant axis about which mechanical motion is referred. The spin-orbit relaxation strongly depends upon the atomic number of the surface atoms and the strength of interaction with the optically pumped atoms. Being dominated by high-atomic-number surface atoms, spin-orbit-relaxation rates may not be too strongly influenced by minor surface contamination of lighter-weight optically active atoms.
Rational use of nonsteroidal anti-inflammatory drugs and proton pump inhibitors in combination for rheumatic diseases

Directory of Open Access Journals (Sweden)

Wolfgang W Bolten

2010-09-01

Full Text Available Wolfgang W BoltenDivision of Rheumatology, Klaus-Miehlke Klinik, Wiesbaden, GermanyAbstract: Nonsteroidal anti-inflammatory drugs (NSAIDs are successfully used to alleviate pain and inflammation in rheumatic diseases. In an appreciable percentage of cases, the use of systemic NSAIDs is associated with adverse lesions of the gastrointestinal (GI mucosa up to life-threatening perforations, ulcers, and bleeding. Reliable warning signals mostly do not arise. Therefore, it is important to take preventive measures to reduce the GI risk. One established method is to assign cyclooxygenase 2 (COX-2-specific inhibitors (coxibs instead of traditional NSAIDs (tNSAIDs. Coxibs spare in part the endogenous gastroprotective mechanisms. Another reliable choice to improve the GI safety is the comedication of proton pump inhibitors (PPIs to suppress gastric acid. A fixed NSAID/PPI combination ensures expected protective effects by improving patients’ PPI adherence and physicians’ PPI prescription persistence. A fixed combination of enteric-coated naproxen and immediate-release esomeprazole has just been approved by the US Food and Drug Administration. PPI combinations with aspirin, other tNSAIDs, and coxibs are desirable. Patients in all risk groups, even patients at low risk of GI adverse events, benefit from concomitant protective measures. Moreover, the literature suggests that NSAID/PPI combinations are cost effective, including for patients in low-GI-risk groups. Pricing of fixed NSAID/PPI combinations will play a pivotal role for their broad acceptance in the future.Keywords: PPI, NSAID, fixed combination, gastrointestinal, adverse events, prevention
Malignant Range Elevation of Serum Chromogranin A due to Inadvertent Use of Proton Pump Inhibitor in a Subject with Pancreatic Incidentaloma

Directory of Open Access Journals (Sweden)

Usman Hammawa Malabu

2011-01-01

Full Text Available We present a case of highly elevated tenfold rise of serum chromogranin A in a young, morbidly obese, hypertensive female being investigated for pancreatic mass, weight loss, and elevated ESR. Following extensive noninvasive investigations, an ultrasound-guided pancreatic biopsy confirmed benign haemorrhagic cyst. A clue to the etiology of the hyperchromogranin A was the elevated serum gastrin level leading to suspicion of proton pump inhibitor administration confirmed by admittance to its use. Withdrawal of the medication led to dramatic resolution of the neuroendocrine tumor marker.
Increasing nuclear safety and operational reliability by upgrading the charging pump mechanical sealing system

International Nuclear Information System (INIS)

Loenhout, Gerard van; Nilsson, Peter; Jehander, Magnus

2016-01-01

For the Ringhals-2 nuclear power plant, three installed centrifugal pumps were designated to have a combined High Head Safety Injection function, as well as a Chemical Volume Control System function. The pumps were originally installed with rubber bellow type mechanical seals, which over time had demonstrated an unreliable sealing performance by displaying high leakages. In 2002, the Ringhals Maintenance engineers initiated to identify a more reliable and robust shaft sealing solution. In 2007, the project was launched and the installation of the first, new mechanical sealing solution took place in the autumn of 2011. In October 2014, these mechanical seals were dismantled and inspected. The inspection confirmed the expected reliability of the new solution.
Increasing nuclear safety and operational reliability by upgrading the charging pump mechanical sealing system

Energy Technology Data Exchange (ETDEWEB)

Loenhout, Gerard van [Flowserve Corporation, Etten-Leur (Netherlands); Nilsson, Peter [Flowsys Technologies AB, Moelndal (Sweden); Jehander, Magnus [Ringhals AB, Vaeroebacka (Sweden)

2016-07-01

For the Ringhals-2 nuclear power plant, three installed centrifugal pumps were designated to have a combined High Head Safety Injection function, as well as a Chemical Volume Control System function. The pumps were originally installed with rubber bellow type mechanical seals, which over time had demonstrated an unreliable sealing performance by displaying high leakages. In 2002, the Ringhals Maintenance engineers initiated to identify a more reliable and robust shaft sealing solution. In 2007, the project was launched and the installation of the first, new mechanical sealing solution took place in the autumn of 2011. In October 2014, these mechanical seals were dismantled and inspected. The inspection confirmed the expected reliability of the new solution.
Increasing nuclear safety and operational reliability by upgrading the charging pump mechanical sealing system

Energy Technology Data Exchange (ETDEWEB)

Loenhout, Gerard van [Flowserve Corporation, Etten-Leur (Netherlands); Nilsson, Peter [Flowsys Technologies AB, Moelndal (Sweden); Jehander, Magnus [Ringhals AB, Vaeroebacka (Sweden)

2016-03-15

For the Ringhals-2 nuclear power plant, three installed centrifugal pumps were designated to have a combined High Head Safety Injection function, as well as a Chemical Volume Control System function. The pumps were originally installed with rubber bellow type mechanical seals, which over time had demonstrated an unreliable sealing performance by displaying high leakages. In 2002, the Ringhals Maintenance engineers initiated to identify a more reliable and robust shaft sealing solution. In 2007, the project was launched and the installation of the first, new mechanical sealing solution took place in the autumn of 2011. In October 2014, these mechanical seals were dismantled and inspected. The inspection confirmed the expected reliability of the new solution.
Formation of M-Like Intermediates in Proteorhodopsin in Alkali Solutions (pH ≥ ∼8.5) Where the Proton Release Occurs First in Contrast to the Sequence at Lower pH.

Science.gov (United States)

Tamogami, Jun; Sato, Keitaro; Kurokawa, Sukuna; Yamada, Takumi; Nara, Toshifumi; Demura, Makoto; Miyauchi, Seiji; Kikukawa, Takashi; Muneyuki, Eiro; Kamo, Naoki

2016-02-23

Proteorhodopsin (PR) is an outward light-driven proton pump observed in marine eubacteria. Despite many structural and functional similarities to bacteriorhodopsin (BR) in archaea, which also acts as an outward proton pump, the mechanism of the photoinduced proton release and uptake is different between two H(+)-pumps. In this study, we investigated the pH dependence of the photocycle and proton transfer in PR reconstituted with the phospholipid membrane under alkaline conditions. Under these conditions, as the medium pH increased, a blue-shifted photoproduct (defined as Ma), which is different from M, with a pKa of ca. 9.2 was produced. The sequence of the photoinduced proton uptake and release during the photocycle was inverted with the increase in pH. A pKa value of ca. 9.5 was estimated for this inversion and was in good agreement with the pKa value of the formation of Ma (∼ 9.2). In addition, we measured the photoelectric current generated by PRs attached to a thin polymer film at varying pH. Interestingly, increases in the medium pH evoked bidirectional photocurrents, which may imply a possible reversal of the direction of the proton movement at alkaline pH. On the basis of these findings, a putative photocycle and proton transfer scheme in PR under alkaline pH conditions was proposed.
Mechanism of pH-dependent activation of the sodium-proton antiporter NhaA

Science.gov (United States)

Huang, Yandong; Chen, Wei; Dotson, David L.; Beckstein, Oliver; Shen, Jana

2016-10-01

Escherichia coli NhaA is a prototype sodium-proton antiporter, which has been extensively characterized by X-ray crystallography, biochemical and biophysical experiments. However, the identities of proton carriers and details of pH-regulated mechanism remain controversial. Here we report constant pH molecular dynamics data, which reveal that NhaA activation involves a net charge switch of a pH sensor at the entrance of the cytoplasmic funnel and opening of a hydrophobic gate at the end of the funnel. The latter is triggered by charging of Asp164, the first proton carrier. The second proton carrier Lys300 forms a salt bridge with Asp163 in the inactive state, and releases a proton when a sodium ion binds Asp163. These data reconcile current models and illustrate the power of state-of-the-art molecular dynamics simulations in providing atomic details of proton-coupled transport across membrane which is challenging to elucidate by experimental techniques.
Molecular basis of proton uptake in single and double mutants of cytochrome c oxidase

Energy Technology Data Exchange (ETDEWEB)

Henry, Rowan M; Caplan, David; Pomes, Regis [Molecular Structure and Function, Hospital for Sick Children, Toronto, ON, M5G 1X8 (Canada); Fadda, Elisa, E-mail: pomes@sickkids.ca [Department of Chemistry, University of Galway (Ireland)

2011-06-15

Cytochrome c oxidase, the terminal enzyme of the respiratory chain, utilizes the reduction of dioxygen into water to pump protons across the mitochondrial inner membrane. The principal pathway of proton uptake into the enzyme, the D channel, is a 2.5 nm long channel-like cavity named after a conserved, negatively charged aspartic acid (D) residue thought to help recruiting protons to its entrance (D132 in the first subunit of the S. sphaeroides enzyme). The single-point mutation of D132 to asparagine (N), a neutral residue, abolishes enzyme activity. Conversely, replacing conserved N139, one-third into the D channel, by D, induces a decoupled phenotype, whereby oxygen reduction proceeds but not proton pumping. Intriguingly, the double mutant D132N/N139D, which conserves the charge of the D channel, restores the wild-type phenotype. We use molecular dynamics simulations and electrostatic calculations to examine the structural and physical basis for the coupling of proton pumping and oxygen chemistry in single and double N139D mutants. The potential of mean force for the conformational isomerization of N139 and N139D side chains reveals the presence of three rotamers, one of which faces the channel entrance. This out-facing conformer is metastable in the wild-type and in the N139D single mutant, but predominant in the double mutant thanks to the loss of electrostatic repulsion with the carboxylate group of D132. The effects of mutations and conformational isomerization on the pKa of E286, an essential proton-shuttling residue located at the top of the D channel, are shown to be consistent with the electrostatic control of proton pumping proposed recently (Fadda et al 2008 Biochim. Biophys. Acta 1777 277-84). Taken together, these results suggest that preserving the spatial distribution of charges at the entrance of the D channel is necessary to guarantee both the uptake and the relay of protons to the active site of the enzyme. These findings highlight the interplay
Molecular basis of proton uptake in single and double mutants of cytochrome c oxidase

International Nuclear Information System (INIS)

Henry, Rowan M; Caplan, David; Pomes, Regis; Fadda, Elisa

2011-01-01

Cytochrome c oxidase, the terminal enzyme of the respiratory chain, utilizes the reduction of dioxygen into water to pump protons across the mitochondrial inner membrane. The principal pathway of proton uptake into the enzyme, the D channel, is a 2.5 nm long channel-like cavity named after a conserved, negatively charged aspartic acid (D) residue thought to help recruiting protons to its entrance (D132 in the first subunit of the S. sphaeroides enzyme). The single-point mutation of D132 to asparagine (N), a neutral residue, abolishes enzyme activity. Conversely, replacing conserved N139, one-third into the D channel, by D, induces a decoupled phenotype, whereby oxygen reduction proceeds but not proton pumping. Intriguingly, the double mutant D132N/N139D, which conserves the charge of the D channel, restores the wild-type phenotype. We use molecular dynamics simulations and electrostatic calculations to examine the structural and physical basis for the coupling of proton pumping and oxygen chemistry in single and double N139D mutants. The potential of mean force for the conformational isomerization of N139 and N139D side chains reveals the presence of three rotamers, one of which faces the channel entrance. This out-facing conformer is metastable in the wild-type and in the N139D single mutant, but predominant in the double mutant thanks to the loss of electrostatic repulsion with the carboxylate group of D132. The effects of mutations and conformational isomerization on the pKa of E286, an essential proton-shuttling residue located at the top of the D channel, are shown to be consistent with the electrostatic control of proton pumping proposed recently (Fadda et al 2008 Biochim. Biophys. Acta 1777 277-84). Taken together, these results suggest that preserving the spatial distribution of charges at the entrance of the D channel is necessary to guarantee both the uptake and the relay of protons to the active site of the enzyme. These findings highlight the interplay
Molecular basis of proton uptake in single and double mutants of cytochrome c oxidase

Science.gov (United States)

Henry, Rowan M.; Caplan, David; Fadda, Elisa; Pomès, Régis

2011-06-01

Cytochrome c oxidase, the terminal enzyme of the respiratory chain, utilizes the reduction of dioxygen into water to pump protons across the mitochondrial inner membrane. The principal pathway of proton uptake into the enzyme, the D channel, is a 2.5 nm long channel-like cavity named after a conserved, negatively charged aspartic acid (D) residue thought to help recruiting protons to its entrance (D132 in the first subunit of the S. sphaeroides enzyme). The single-point mutation of D132 to asparagine (N), a neutral residue, abolishes enzyme activity. Conversely, replacing conserved N139, one-third into the D channel, by D, induces a decoupled phenotype, whereby oxygen reduction proceeds but not proton pumping. Intriguingly, the double mutant D132N/N139D, which conserves the charge of the D channel, restores the wild-type phenotype. We use molecular dynamics simulations and electrostatic calculations to examine the structural and physical basis for the coupling of proton pumping and oxygen chemistry in single and double N139D mutants. The potential of mean force for the conformational isomerization of N139 and N139D side chains reveals the presence of three rotamers, one of which faces the channel entrance. This out-facing conformer is metastable in the wild-type and in the N139D single mutant, but predominant in the double mutant thanks to the loss of electrostatic repulsion with the carboxylate group of D132. The effects of mutations and conformational isomerization on the pKa of E286, an essential proton-shuttling residue located at the top of the D channel, are shown to be consistent with the electrostatic control of proton pumping proposed recently (Fadda et al 2008 Biochim. Biophys. Acta 1777 277-84). Taken together, these results suggest that preserving the spatial distribution of charges at the entrance of the D channel is necessary to guarantee both the uptake and the relay of protons to the active site of the enzyme. These findings highlight the interplay

Obesity does not affect treatment outcomes with proton pump inhibitors.

Science.gov (United States)

Sharma, Prateek; Vakil, Nimish; Monyak, John T; Silberg, Debra G

2013-09-01

Obesity is associated with increased risk of gastroesophageal reflux disease (GERD). To evaluate the effect of obesity on symptom resolution in patients with nonerosive reflux disease (NERD) and healing rates in patients with erosive esophagitis (EE). Two post hoc analyses were performed. Analyses included pooled data from randomized, double-blind, multicenter studies of proton pump inhibitors (PPIs) in GERD patients. Analysis 1 included 704 patients with NERD receiving esomeprazole 20 mg, esomeprazole 40 mg, or placebo. Analysis 2 included 11,027 patients with EE receiving esomeprazole 40 mg, omeprazole 20 mg, or lansoprazole 30 mg. For NERD patients, no significant association between baseline heartburn severity and body mass index (BMI) was observed. In EE patients, overweight (BMI 25 to <35 kg/m) and obese (BMI ≥35 kg/m) patients had significantly higher rates of Los Angeles (LA) grade C or D EE than patients with BMI <25 kg/m (P<0.0001). Percentages of PPI-treated patients who achieved heartburn resolution or EE healing within a given LA grade were similar across BMI categories. Heartburn resolution was significantly associated with treatment (esomeprazole vs. placebo), increasing age, and for men versus women (all P≤0.0284). EE healing was significantly associated with PPI treatment (esomeprazole and lansoprazole vs. omeprazole), increasing age, race, presence of a hiatal hernia, and lower LA grade at baseline (all P≤0.0183). In patients with GERD, high BMI was associated with more severe EE at baseline. However, during PPI treatment, BMI is not a significant independent predictor of heartburn resolution or EE healing.
Exploring the entrance of proton pathways in cytochrome c oxidase from Paracoccus denitrificans: surface charge, buffer capacity and redox-dependent polarity changes at the internal surface.

Science.gov (United States)

Kirchberg, Kristina; Michel, Hartmut; Alexiev, Ulrike

2013-03-01

Cytochrome c oxidase (CcO), the terminal oxidase of cellular respiration, reduces molecular oxygen to water. The mechanism of proton pumping as well as the coupling of proton and electron transfer is still not understood in this redox-linked proton pump. Eleven residues at the aqueous-exposed surfaces of CcO from Paracoccus denitrificans have been exchanged to cysteines in a two-subunit base variant to yield single reactive cysteine variants. These variants are designed to provide unique labeling sites for probes to be used in spectroscopic experiments investigating the mechanism of proton pumping in CcO. To this end we have shown that all cysteine variants are enzymatically active. Cysteine positions at the negative (N-) side of the membrane are located close to the entrance of the D- and K-proton transfer pathways that connect the N-side with the catalytic oxygen reduction site. Labeling of the pH-indicator dye fluorescein to these sites allowed us to determine the surface potential at the cytoplasmic CcO surface, which corresponds to a surface charge density of -0.5 elementary charge/1000Å(2). In addition, acid-base titrations revealed values of CcO buffer capacity. Polarity measurements of the label environment at the N-side provided (i) site-specific values indicative of a hydrophilic and a more hydrophobic environment dependent on the label position, and (ii) information on a global change to a more apolar environment upon reduction of the enzyme. Thus, the redox state of the copper and heme centers inside the hydrophobic interior of CcO affect the properties at the cytoplasmic surface. Copyright © 2012 Elsevier B.V. All rights reserved.
The influence of proton pump inhibitors and other commonly used medication on the gut microbiota.

Science.gov (United States)

Imhann, Floris; Vich Vila, Arnau; Bonder, Marc Jan; Lopez Manosalva, Ailine G; Koonen, Debby P Y; Fu, Jingyuan; Wijmenga, Cisca; Zhernakova, Alexandra; Weersma, Rinse K

2017-07-04

Proton pump inhibitors (PPIs), used to treat gastro-esophageal reflux and prevent gastric ulcers, are among the most widely used drugs in the world. The use of PPIs is associated with an increased risk of enteric infections. Since the gut microbiota can, depending on composition, increase or decrease the risk of enteric infections, we investigated the effect of PPI-use on the gut microbiota. We discovered profound differences in the gut microbiota of PPI users: 20% of their bacterial taxa were statistically significantly altered compared with those of non-users. Moreover, we found that it is not only PPIs, but also antibiotics, antidepressants, statins and other commonly used medication were associated with distinct gut microbiota signatures. As a consequence, commonly used medications could affect how the gut microbiota resist enteric infections, promote or ameliorate gut inflammation, or change the host's metabolism. More studies are clearly needed to understand the role of commonly used medication in altering the gut microbiota as well as the subsequent health consequences.
Is there an overprescription of proton pump inhibitors in oncohematologic patients undergoing ambulatory oncospecific treatment?

Directory of Open Access Journals (Sweden)

Meritxell Pujal Herranz

2016-09-01

Full Text Available Objective: The aim of this study is to evaluate the prevalence of proton pump inhibitors (PPIs prescription, and the level of adequacy of the indication of these drugs in oncohematologic patients under ambulatory oncoespecific treatment. Method: An observational descriptive study in oncohematologic patients under ambulatory oncoespecific treatment. A protocol for the rational use of PPI targeted to oncohematologic patients based on the PPI protocol of our hospital was designed. Patients under active treatment with PPIs were quantified and the appropriateness of their indications evaluated. Results: 111 patients (71 oncologic and 40 hematologic were included. 56% of all oncologic patients and 63% of all hematologic patients were under active treatment with PPIs. After reviewing the indications for PPI in all patients, 72% of oncologic and 12% of hematologic patients did not present evidence justifying treatment with these drugs. Conclusion: It is important the pharmacist to detect unappropriated prescriptions of PPIs, especially among oncologic patients, and to promote a deprescription of these drugs
Inservice testing of vertical pumps

International Nuclear Information System (INIS)

Cornman, R.E. Jr.; Schumann, K.E.

1994-01-01

This paper focuses on the problems that may occur with vertical pumps while inservice tests are conducted in accordance with existing American Society of Mechanical Engineers Code, Section XI, standards. The vertical pump types discussed include single stage, multistage, free surface, and canned mixed flow pumps. Primary emphasis is placed on the hydraulic performance of the pump and the internal and external factors to the pump that impact hydraulic performance. In addition, the paper considers the mechanical design features that can affect the mechanical performance of vertical pumps. The conclusion shows how two recommended changes in the Code standards may increase the quality of the pump's operational readiness assessment during its service life
Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial)

DEFF Research Database (Denmark)

Krag, Mette; Perner, Anders; Wetterslev, Jørn

2016-01-01

BACKGROUND: Critically ill patients in the intensive care unit (ICU) are at risk of clinically important gastrointestinal bleeding, and acid suppressants are frequently used prophylactically. However, stress ulcer prophylaxis may increase the risk of serious adverse events and, additionally......, the quantity and quality of evidence supporting the use of stress ulcer prophylaxis is low. The aim of the SUP-ICU trial is to assess the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the ICU. We hypothesise that stress ulcer prophylaxis reduces the rate...... of gastrointestinal bleeding, but increases rates of nosocomial infections and myocardial ischaemia. The overall effect on mortality is unpredictable. METHODS/DESIGN: The SUP-ICU trial is an investigator-initiated, pragmatic, international, multicentre, randomised, blinded, parallel-group trial of stress ulcer...
Rikkunshito improves globus sensation in patients with proton-pump inhibitor-refractory laryngopharyngeal reflux.

Science.gov (United States)

Tokashiki, Ryoji; Okamoto, Isaku; Funato, Nobutoshi; Suzuki, Mamoru

2013-08-21

To investigate the effect of rikkunshito on laryngopharyngeal reflux (LPR) symptoms and gastric emptying in patients with proton-pump inhibitor (PPI)-refractory LPR. In total, 22 patients with LPR were enrolled. Following a 2-wk treatment with PPI monotherapy, PPI-refractory LPR patients were randomly divided into two treatment groups (rikkunshito alone or rikkunshito plus the PPI, lansoprazole). LPR symptoms were assessed using a visual analog scale (VAS) score, gastrointestinal symptoms were assessed using the gastrointestinal symptom rating scale (GSRS), and gastric emptying was assessed using the radio-opaque marker method prior to and 4 wk following treatments. The 4-wk treatment with rikkunshito alone and with rikkunshito plus the PPI significantly decreased the globus sensation VAS scores. The VAS score for sore throat was significantly decreased following treatment with rikkunshito plus PPI but not by rikkunshito alone. Neither treatment significantly changed the GSRS scores. Rikkunshito improved delayed gastric emptying. We found a significant positive correlation between improvements in globus sensation and in gastric emptying (r² = 0.4582, P sensation in patients with PPI-refractory LPR, in part, because of stimulation of gastric emptying. Thus, rikkunshito is an effective treatment for PPI-refractory LPR.
Residual heat removal pump and low pressure safety injection pump retrofit program

International Nuclear Information System (INIS)

Dudiak, J.G.; McKenna, J.M.

1992-01-01

Residual Heat Removal (RHR) and low pressure safety injection (LPSI) pumps installed in pressurized water-to-reactor power plants are used to provide low-head safety injection in the event of loss of coolant in the reactor coolant system. Because these pumps are subjected to rather severe temperature and pressure transients, the majority of pumps installed in the RHR service are vertical pumps with a single stage impeller. Typically the pump impeller is mounted on an extended motor shaft (close-coupled configuration) and a mechanical seal is employed at the pump end of the shaft. Traditionally RHR and LPSI pumps have been a significant maintenance item for many utilities. Periodic mechanical seal of motor bearing replacement often is considered routine maintenance. The closed-coupled pump design requires disassembly of the casing cover from the lower pump casing while performing these routine maintenance tasks. This paper introduces a design modification developed to convert the close-coupled RHR and LPSI pumps to a coupled configuration
Hemocompatibility of Axial Versus Centrifugal Pump Technology in Mechanical Circulatory Support Devices.

Science.gov (United States)

Schibilsky, David; Lenglinger, Matthias; Avci-Adali, Meltem; Haller, Christoph; Walker, Tobias; Wendel, Hans Peter; Schlensak, Christian

2015-08-01

The hemocompatible properties of rotary blood pumps commonly used in mechanical circulatory support (MCS) are widely unknown regarding specific biocompatibility profiles of different pump technologies. Therefore, we analyzed the hemocompatibility indicating markers of an axial flow and a magnetically levitated centrifugal device within an in vitro mock loop. The HeartMate II (HM II; n = 3) device and a CentriMag (CM; n = 3) adult pump were investigated in a human whole blood mock loop for 360 min using the MCS devices as a driving component. Blood samples were analyzed by enzyme-linked immunosorbent assay for markers of coagulation, complement system, and inflammatory response. There was a time-dependent activation of the coagulation (thrombin-antithrombin complexes [TAT]), complement (SC5b-9), and inflammation system (polymorphonuclear [PMN] elastase) in both groups. The mean value of TAT (CM: 4.0 μg/L vs. 29.4 μg/L, P technologies and a magnetically levitated centrifugal pump design might be superior. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals Inc.
Nitric oxide contributes to minerals absorption, proton pumps and hormone equilibrium under cadmium excess in Trifolium repens L. plants.

Science.gov (United States)

Liu, Shiliang; Yang, Rongjie; Pan, Yuanzhi; Ma, Mingdong; Pan, Jiang; Zhao, Yan; Cheng, Qingsu; Wu, Mengxi; Wang, Maohua; Zhang, Lin

2015-09-01

Nitric oxide (NO) is a stress-signaling molecule in plants that mediates a wide range of physiological processes and responses to metal toxicity. In this work, various NO modulators (NO donor: SNP; NO scavenger: cPTIO; NO synthase inhibitor: l-NAME; and SNP analogs: sodium nitrite/nitrate and sodium ferrocyanide) were investigated to determine the role of NO in Trifolium repens L. plants exposed to Cd. Cd (100μM) markedly reduced biomass, NO production and chlorophyll (Chl a, Chl b and total Chl) concentration but stimulated reactive oxygen species (ROS) and Cd accumulation in plants. SNP (50μM) substantially attenuated growth inhibition, reduced hydrogen peroxide (H2O2) and malonyldialdehyde (MDA) levels, stimulated ROS-scavenging enzymes/agents, and mitigated the H(+)-ATPase inhibition in proton pumps. Interestingly, SNP considerably up-regulated the levels of jasmonic acid (JA) and proline in plant tissues but down-regulated the levels of ethylene (ET) in both shoots and roots and the level of salicylic acid (SA) in roots only, which might be related to the elevated NO synthesis. Additionally, SNP (25-200μM) regulated mineral absorption and, particularly at 50μM, significantly enhanced the uptake of shoot magnesium (Mg) and copper (Cu) and of root calcium (Ca), Mg and iron (Fe). Nevertheless, the effects of SNP on plant growth were reversed by cPTIO and l-NAME, suggesting that the protective effect of SNP might be associated with NO synthesis in vivo. Moreover, SNP analogs did not display roles similar to that of SNP. These results indicated that NO depleted Cd toxicity by eliminating oxidative damage, enhancing minerals absorption, regulating proton pumps, and maintaining hormone equilibrium. Copyright © 2015 Elsevier Inc. All rights reserved.
Proton pump inhibitors therapy vs H2 receptor antagonists therapy for upper gastrointestinal bleeding after endoscopy: A meta-analysis.

Science.gov (United States)

Zhang, Ying-Shi; Li, Qing; He, Bo-Sai; Liu, Ran; Li, Zuo-Jing

2015-05-28

To compare the therapeutic effects of proton pump inhibitors vs H₂ receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy. We searched the Cochrane library, MEDLINE, EMBASE and PubMed for randomized controlled trials until July 2014 for this study. The risk of bias was evaluated by the Cochrane Collaboration's tool and all of the studies had acceptable quality. The main outcomes included mortality, re-bleeding, received surgery rate, blood transfusion units and hospital stay time. These outcomes were estimated using odds ratios (OR) and mean difference with 95% confidence interval (CI). RevMan 5.3.3 software and Stata 12.0 software were used for data analyses. Ten randomized controlled trials involving 1283 patients were included in this review; 678 subjects were in the proton pump inhibitors (PPI) group and the remaining 605 subjects were in the H₂ receptor antagonists (H₂RA) group. The meta-analysis results revealed that after successful endoscopic therapy, compared with H₂RA, PPI therapy had statistically significantly decreased the recurrent bleeding rate (OR = 0.36; 95%CI: 0.25-0.51) and receiving surgery rate (OR = 0.29; 95%CI: 0.09-0.96). There were no statistically significant differences in mortality (OR = 0.46; 95%CI: 0.17-1.23). However, significant heterogeneity was present in both the numbers of patients requiring blood transfusion after treatment [weighted mean difference (WMD), -0.70 unit; 95%CI: -1.64 - 0.25] and the time that patients remained hospitalized [WMD, -0.77 d; 95%CI: -1.87 - 0.34]. The Begg's test (P = 0.283) and Egger's test (P = 0.339) demonstrated that there was no publication bias in our meta-analysis. In patients with upper gastrointestinal bleeding after successful endoscopic therapy, compared with H₂RA, PPI may be a more effective therapy.
Clinical value of wireless pH-monitoring of gastro-esophageal reflux in children before and after proton pump inhibitors.

Science.gov (United States)

Boström, Michaela; Thorsson, Ola; Toth, Ervin; Agardh, Daniel

2014-12-24

Wireless pH-monitoring is an accurate method for diagnosing adults with gastroesophageal reflux disease (GERD). The aim of this study was to evaluate the use of the Bravo capsule on children investigated for GERD in terms of safety, tolerability and feasibility before and after administration of proton pump inhibitors. A Bravo capsule was inserted during upper endoscopy under general anaesthesia or deep sedation with propofol. 48-hour pH-metry was performed in 106 children (50 males, 56 females) at the median age of 11 years (range 17 months-18 years). On the second day of investigation, proton pump inhibitor (PPI) was given at a mean dose of 1.6 mg/kg (SD ±0.6 mg). The definition of GERD was set to a reflux index (RI) of ≥5% and DeMeester score (DMS) ≥14.7. Application of the capsule was successful in 103 of the 106 children (97.2%) and interpretable in 99 of these 103 (96.1%). 49 of the children with interpretable results (49.5%) had GERD according to RI, while 51 (56.7%) had GERD according to DMS. After PPI was given on day 2, RI decreased from a median of 4.9% (range 0.3-63.4%) to 2.2% (0-58.0%), while DMS decreased from a median of 17.6 (range 2.2-207.6) to 8.2 (0.3-178.6), respectively (p < 0.0001). No severe adverse events were reported. Wireless pH-metry is a safe and tolerable method when investigating children for GERD. PPI given on the second day of assessment provides additional information on response to treatment suggesting that pH-metry preferably should be extended to 48 hours.
Proton transfer events in GFP.

Science.gov (United States)

Di Donato, Mariangela; van Wilderen, Luuk J G W; Van Stokkum, Ivo H M; Stuart, Thomas Cohen; Kennis, John T M; Hellingwerf, Klaas J; van Grondelle, Rienk; Groot, Marie Louise

2011-09-28

Proton transfer is one of the most important elementary processes in biology. Green fluorescent protein (GFP) serves as an important model system to elucidate the mechanistic details of this reaction, because in GFP proton transfer can be induced by light absorption. Illumination initiates proton transfer through a 'proton-wire', formed by the chromophore (the proton donor), water molecule W22, Ser205 and Glu222 (the acceptor), on a picosecond time scale. To obtain a more refined view of this process, we have used a combined approach of time resolved mid-infrared spectroscopy and visible pump-dump-probe spectroscopy to resolve with atomic resolution how and how fast protons move through this wire. Our results indicate that absorption of light by GFP induces in 3 ps (10 ps in D(2)O) a shift of the equilibrium positions of all protons in the H-bonded network, leading to a partial protonation of Glu222 and to a so-called low barrier hydrogen bond (LBHB) for the chromophore's proton, giving rise to dual emission at 475 and 508 nm. This state is followed by a repositioning of the protons on the wire in 10 ps (80 ps in D(2)O), ultimately forming the fully deprotonated chromophore and protonated Glu222.
Phytoremediation potential of Arabidopsis thaliana, expressing ectopically a vacuolar proton pump, for the industrial waste phosphogypsum.

Science.gov (United States)

Khoudi, Habib; Maatar, Yafa; Brini, Faïçal; Fourati, Amine; Ammar, Najoua; Masmoudi, Khaled

2013-01-01

Phosphogypsum (PG) is a by-product of the phosphorus-fertiliser industry and represents an environmental concern since it contains pollutants such as cadmium (Cd). We have recently shown that the overexpression of a proton pump gene (TaVP1) in transgenic tobacco (Nicotiana tabacum) led to an enhanced Cd tolerance and accumulation. The aim of this study was to evaluate the potential of transgenic Arabidopsis thaliana plants harbouring the TaVP1 gene to phytoremediate phosphogypsum. A pot experiment was carried out under greenhouse conditions. Transgenic A. thaliana plants harbouring the TaVP1 gene were grown on various substrates containing phosphogypsum (0, 25, 50 and 100 %) for 40 days. At the end of the growth period, we examined the growth (germination, root length, fresh weight) and physiological parameters (chlorophyll and protein contents, catalase activity and proteolysis) as well as the cadmium, Mg, Ca, and P contents of the A. thaliana plants. In order to evaluate Cd tolerance of the A. thaliana lines harbouring the TaVP1 gene, an in vitro experiment was also carried out. One week-old seedlings were transferred to Murashige and Skoog agar plates containing various concentrations of cadmium; the germination, total leaf area and root length were determined. The growth and physiological parameters of all A. thaliana plants were significantly altered by PG. The germination capacity, root growth and biomass production of wild-type (WT) plants were more severely inhibited by PG compared with the TaVP1 transgenic A. thaliana lines. In addition, TaVP1 transgenic A. thaliana plants maintained a higher antioxidant capacity than the WT. Interestingly, elemental analysis of leaf material derived from plants grown on PG revealed that the transgenic A. thaliana line accumulated up to ten times more Cd than WT. Despite its higher Cd content, the transgenic A. thaliana line performed better than the WT counterpart. In vitro evaluation of Cd tolerance showed that TaVP1
Fundamental Insights into Proton-Coupled Electron Transfer in Soybean Lipoxygenase from Quantum Mechanical/Molecular Mechanical Free Energy Simulations.

Science.gov (United States)

Li, Pengfei; Soudackov, Alexander V; Hammes-Schiffer, Sharon

2018-02-28

The proton-coupled electron transfer (PCET) reaction catalyzed by soybean lipoxygenase has served as a prototype for understanding hydrogen tunneling in enzymes. Herein this PCET reaction is studied with mixed quantum mechanical/molecular mechanical (QM/MM) free energy simulations. The free energy surfaces are computed as functions of the proton donor-acceptor (C-O) distance and the proton coordinate, and the potential of mean force is computed as a function of the C-O distance, inherently including anharmonicity. The simulation results are used to calculate the kinetic isotope effects for the wild-type enzyme (WT) and the L546A/L754A double mutant (DM), which have been measured experimentally to be ∼80 and ∼700, respectively. The PCET reaction is found to be exoergic for WT and slightly endoergic for the DM, and the equilibrium C-O distance for the reactant is found to be ∼0.2 Å greater for the DM than for WT. The larger equilibrium distance for the DM, which is due mainly to less optimal substrate binding in the expanded binding cavity, is primarily responsible for its higher kinetic isotope effect. The calculated potentials of mean force are anharmonic and relatively soft at shorter C-O distances, allowing efficient thermal sampling of the shorter distances required for effective hydrogen tunneling. The primarily local electrostatic field at the transferring hydrogen is ∼100 MV/cm in the direction to facilitate proton transfer and increases dramatically as the C-O distance decreases. These simulations suggest that the overall protein environment is important for conformational sampling of active substrate configurations aligned for proton transfer, but the PCET reaction is influenced primarily by local electrostatic effects that facilitate conformational sampling of shorter proton donor-acceptor distances required for effective hydrogen tunneling.
Pump failure leads to alternative vertical pump condition monitoring technique

International Nuclear Information System (INIS)

DeVilliers, Adriaan; Glandon, Kevin

2011-01-01

Condition monitoring and detecting early signs of potential failure mechanisms present particular problems in vertical pumps. Most often, the majority of the pump assembly is not readily accessible for visual or audible inspection or conventional vibration monitoring techniques using accelerometers and/or proximity sensors. The root cause failure analysis of a 2-stage vertical centrifugal service-water pump at a nuclear power generating facility in the USA is presented, highlighting this long standing challenge in condition monitoring of vertical pumps. This paper will summarize the major findings of the root cause analysis (RCA), highlight the limitations of traditional monitoring techniques, and present an expanded application of motor current monitoring as a means to gain insight into the mechanical performance and condition of a pump. The 'real-world' example of failure, monitoring and correlation of the monitoring technique to a detailed pump disassembly inspection is also presented. This paper will explain some of the reasons behind well known design principles requiring natural frequency separation from known forcing frequencies, as well as explore an unexpected submerged brittle fracture failure mechanism, and how such issues may be avoided. (author)
Bimolecular reactions of carbenes: Proton transfer mechanism

Science.gov (United States)

Abu-Saleh, Abd Al-Aziz A.; Almatarneh, Mansour H.; Poirier, Raymond A.

2018-04-01

Here we report the bimolecular reaction of trifluoromethylhydroxycarbene conformers and the water-mediated mechanism of the 1,2-proton shift for the unimolecular trans-conformer by using quantum chemical calculations. The CCSD(T)/cc-pVTZ//MP2/cc-pVDZ potential-energy profile of the bimolecular reaction of cis- and trans-trifluoromethylhydroxycarbene, shows the lowest gas-phase barrier height of 13 kJ mol-1 compared to the recently reported value of 128 kJ mol-1 for the unimolecular reaction. We expect bimolecular reactions of carbene's stereoisomers will open a valuable field for new and useful synthetic strategies.
Development of urinary incontinence in a 7-year old boy after therapy with proton pump inhibitors and complete resolution of his clinicopathologic features of eosinophilic esophagitis after H2-receptor antagonist treatment: A case report

Directory of Open Access Journals (Sweden)

Rok Orel

2017-06-01

Full Text Available Background: Several diseases result in profound infltration of esophageal mucosa by eosinophilic granulocites, with gastroesophageal reﬂux disease (GERD, eosinophilic esophagitis (EoE and proton-pump-inhibitor-responsive esophageal eosinophilia (PPI-REE being the most prevalent. Proton-pump-inhibitor-responsive esophageal eosinophilia (PPI-REE is a newly recognized entity that must be diﬀerentiated from eosinophilic esophagitis (EoE.Case presentation: A 7-year old Slovenian male presented with a few-month history of chest pain, regurgitation and heartburn. First endoscopy was performed and revealed pronounced longitudinal furrows, and on hystology examination > 70 eosinophils per high power feld were found through the entire thickness of epithelium and in the submucosis with eosinophilic microabscess formation. Results of 24-hour pH-monitoring (without impedance monitoring excluded pathologic acid reﬂux. All allergy tests were negative. Te patient started treatment with proton pump inhibitors (PPIs for three times, twice with pantoprazole before the endoscopy and once with esomeprazole after it to exclude the diagnosis of GERD and PPI-REE. Urinary incontinence reappeared each time just few days after starting treatment and disappeared few days after stopping it. Therefore, urinary incontinence was considered as a plausible adverse eﬀect of therapy with PPIs. As treatment with PPIs was not tolerated, a therapy with H2-receptor antagonists ranitidine was applied for more than 2 months followed by a second endoscopy. Both symptoms and esophageal eosinophilia completely resolved with ranitidine. The resolution of esophageal eosinophilia in PPI-REE has been attributed to proton pump independent antiinﬂammatory eﬀects of PPIs. No such eﬀects have been described in H2-receptor antagonists.Conclusions: Two unique phenomena were observed in the pediatric patient with profound esophageal eosinophilia: urinary incontinence as an adverse e�
Decreasing incidence of peptic ulcer complications after the introduction of the proton pump inhibitors, a study of the Swedish population from 1974–2002

Directory of Open Access Journals (Sweden)

Ranstam Jonas

2009-04-01

Full Text Available Abstract Background Despite a decreasing incidence of peptic ulcer disease, most previous studies report a stabile incidence of ulcer complications. We wanted to investigate the incidence of peptic ulcer complications in Sweden before and after the introduction of the proton pump inhibitors (PPI in 1988 and compare these data to the sales of non-steroid anti-inflammatory drugs (NSAID and acetylsalicylic acid (ASA. Methods All cases of gastric and duodenal ulcer complications diagnosed in Sweden from 1974 to 2002 were identified using the National hospital discharge register. Information on sales of ASA/NSAID was obtained from the National prescription survey. Results When comparing the time-periods before and after 1988 we found a significantly lower incidence of peptic ulcer complications during the later period for both sexes (p Conclusion When comparing the periods before and after the introduction of the proton pump inhibitors we found a significant decrease in the incidence of peptic ulcer complications in the Swedish population after 1988 when PPI were introduced on the market. The cause of this decrease is most likely multifactorial, including smoking habits, NSAID consumption, prevalence of Helicobacter pylori and the introduction of PPI. Sales of prescribed NSAID/ASA increased, especially in middle-aged and elderly women. This fact seems to have had little effect on the incidence of peptic ulcer complications.
RND-type Drug Efflux Pumps from Gram-negative bacteria: Molecular Mechanism and Inhibition

Directory of Open Access Journals (Sweden)

Henrietta eVenter

2015-04-01

Full Text Available Drug efflux protein complexes confer multidrug resistance on bacteria by transporting a wide spectrum of structurally diverse antibiotics. Moreover, organisms can only acquire resistance in the presence of an active efflux pump. The substrate range of drug efflux pumps is not limited to antibiotics, but it also includes toxins, dyes, detergents, lipids and molecules involved in quorum sensing; hence efflux pumps are also associated with virulence and biofilm formation. Inhibitors of efflux pumps are therefore attractive compounds to reverse multidrug resistance and to prevent the development of resistance in clinically relevant bacterial pathogens. Recent successes on the structure determination and functional analysis of the AcrB and MexB components of the AcrAB-TolC and MexAB-OprM drug efflux systems as well as the structure of the fully assembled, functional triparted AcrAB-TolC complex significantly contributed to our understanding of the mechanism of substrate transport and the options for inhibition of efflux. These data, combined with the well-developed methodologies for measuring efflux pump inhibition, could allow the rational design and subsequent experimental verification of potential efflux pump inhibitors. In this review we will explore how the available biochemical and structural information can be translated into the discovery and development of new compounds that could reverse drug resistance in Gram-negative pathogens. The current literature on efflux pump inhibitors will also be analysed and the reasons why no compounds have yet progressed into clinical use will be explored.

Potential association between the recent increase in campylobacteriosis incidence in the Netherlands and proton-pump inhibitor use - an ecological study.

Science.gov (United States)

Bouwknegt, M; van Pelt, W; Kubbinga, M E; Weda, M; Havelaar, A H

2014-08-14

The Netherlands saw an unexplained increase in campylobacteriosis incidence between 2003 and 2011, following a period of continuous decrease. We conducted an ecological study and found a statistical association between campylobacteriosis incidence and the annual number of prescriptions for proton pump inhibitors (PPIs), controlling for the patient's age, fresh and frozen chicken purchases (with or without correction for campylobacter prevalence in fresh poultry meat). The effect of PPIs was larger in the young than in the elderly. However, the counterfactual population-attributable fraction for PPIs was largest for the elderly (ca 45% in 2011) and increased at population level from 8% in 2004 to 27% in 2011. Using the regression model and updated covariate values, we predicted a trend break for 2012, largely due to a decreased number of PPI prescriptions, that was subsequently confirmed by surveillance data. Although causality was not shown, the biological mechanism, age effect and trend-break prediction suggest a substantial impact of PPI use on campylobacteriosis incidence in the Netherlands. We chose the ecological study design to pilot whether it is worthwhile to further pursue the effect of PPI on campylobacteriosis and other gastrointestinal pathogens in prospective cohort studies. We now provide strong arguments to do so.
Mechanism for the Excited-State Multiple Proton Transfer Process of Dihydroxyanthraquinone Chromophores.

Science.gov (United States)

Zhou, Qiao; Du, Can; Yang, Li; Zhao, Meiyu; Dai, Yumei; Song, Peng

2017-06-22

The single and dual cooperated proton transfer dynamic process in the excited state of 1,5-dihydroxyanthraquinone (1,5-DHAQ) was theoretically investigated, taking solvent effects (ethanol) into account. The absorption and fluorescence spectra were simulated, and dual fluorescence exhibited, which is consistent with previous experiments. Analysis of the calculated IR and Raman vibration spectra reveals that the intramolecular hydrogen bonding interactions (O 20 -H 21 ···O 24 and O 22 -H 23 ···O 25 ) are strengthened following the excited proton transfer process. Finally, by constructing the potential energy surfaces of the ground state, first excited singlet state, and triplet state, the mechanism of the intramolecular proton transfer of 1,5-DHAQ can be revealed.
Proton pump inhibitors while belonging to the same family of generic drugs show different anti-tumor effect.

Science.gov (United States)

Lugini, Luana; Federici, Cristina; Borghi, Martina; Azzarito, Tommaso; Marino, Maria Lucia; Cesolini, Albino; Spugnini, Enrico Pierluigi; Fais, Stefano

2016-08-01

Tumor acidity represents a major cause of chemoresistance. Proton pump inhibitors (PPIs) can neutralize tumor acidity, sensitizing cancer cells to chemotherapy. To compare the anti-tumor efficacy of different PPIs in vitro and in vivo. In vitro experiments PPIs anti-tumor efficacy in terms of cell proliferation and cell death/apoptosis/necrosis evaluation were performed. In vivo PPIs efficacy experiments were carried out using melanoma xenograft model in SCID mice. Lansoprazole showed higher anti-tumor effect when compared to the other PPIs. The lansoprazole effect lasted even upon drug removal from the cell culture medium and it was independent from the lipophilicity of the PPIs formulation. These PPIs have shown different anti-tumoral efficacy, and the most effective at low dose was lansoprazole. The possibility to contrast tumor acidity by off-label using PPIs opens a new field of oncology investigation.
Tritium Sequestration in Gen IV NGNP Gas Stream via Proton Conducting Ceramic Pumps

Energy Technology Data Exchange (ETDEWEB)

Chen, Fanglin Frank [Univ. of South Carolina, Columbia, SC (United States); Adams, Thad M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Brinkman, Kyle [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Reifsnider, Kenneth [Univ. of South Carolina, Columbia, SC (United States)

2011-09-30

Several types of high-temperature proton conductors based on SrCeO₃ and BaCeO₃ have been systematically investigated in this project for tritium separation in NGNP applications. One obstacle for the field application is the chemical stability issues in the presence of steam and CO₂ for these proton conductors. Several strategies to overcome such issues have been evaluated, including A site doping and B site co-doping method for perovskite-structured proton conductors. Novel zirconium-free proton conductors have also been developed with improved electrical conductivity and enhanced chemical stability. Novel catalytic materials for the proton-conducting separation membranes have been investigated. A tubular geometry proton-conducting membrane has been developed for the proton separation membranes. Total dose rate estimated from tritium decay (beta emission) under realistic membrane operating conditions, combined with electron irradiation experiments, indicates that proton ceramic materials possess the appropriate radiation stability for this application.
Optical silencing of body wall muscles induces pumping inhibition in Caenorhabditis elegans

OpenAIRE

Takahashi, Megumi; Takagi, Shin

2017-01-01

Feeding, a vital behavior in animals, is modulated depending on internal and external factors. In the nematode Caenorhabditis elegans, the feeding organ called the pharynx ingests food by pumping driven by the pharyngeal muscles. Here we report that optical silencing of the body wall muscles, which drive the locomotory movement of worms, affects pumping. In worms expressing the Arch proton pump or the ACR2 anion channel in the body wall muscle cells, the pumping rate decreases after activatio...
Detection of pump degradation

International Nuclear Information System (INIS)

Casada, D.A.

1994-01-01

There are a variety of stressors that can affect the operation of centrifugal pumps. These can generally be classified as: Mechanical; Hydraulic; Tribological; Chemical; and Other (including those associated with the pump driver). Although these general stressors are active in essentially all centrifugal pumps, the stressor level and the extent of wear and degradation can vary greatly. Parameters that affect the extent of stressor activity are manifold. In order to assure the long-term operational readiness of a pump, it is important to both understand the nature and magnitude of the specific degradation mechanisms and to monitor the performance of the pump
Proton-pump inhibitor use does not affect semen quality in subfertile men

Directory of Open Access Journals (Sweden)

Sorena Keihani

2018-01-01

Full Text Available Proton-pump inhibitors (PPIs are among the most widely used drugs worldwide. PPI use has recently been linked to adverse changes in semen quality in healthy men; however, the effects of PPI use on semen parameters remain largely unknown specifically in cases with male factor infertility. We examined whether PPI use was associated with detrimental effects on semen parameters in a large population of subfertile men. We retrospectively reviewed data from 12 257 subfertile men who had visited our fertility clinic from 2003 to 2013. Patients who reported using any PPIs for >3 months before semen sample collection were included; 7698 subfertile men taking no medication served as controls. Data were gathered on patient age, medication use, and conventional semen parameters; patients taking any known spermatotoxic medication were excluded. Linear mixed-effect regression models were used to test the effect of PPI use on semen parameters adjusting for age. A total of 248 patients (258 samples used PPIs for at least 3 months before semen collection. In regression models, PPI use (either as the only medication or when used in combination with other nonspermatotoxic medications was not associated with statistically significant changes in semen parameters. To our knowledge, this is the largest study to compare PPI use with semen parameters in subfertile men. Using PPIs was not associated with detrimental effects on semen quality in this retrospective study.
Proton-pump inhibitor use does not affect semen quality in subfertile men.

Science.gov (United States)

Keihani, Sorena; Craig, James R; Zhang, Chong; Presson, Angela P; Myers, Jeremy B; Brant, William O; Aston, Kenneth I; Emery, Benjamin R; Jenkins, Timothy G; Carrell, Douglas T; Hotaling, James M

2018-01-01

Proton-pump inhibitors (PPIs) are among the most widely used drugs worldwide. PPI use has recently been linked to adverse changes in semen quality in healthy men; however, the effects of PPI use on semen parameters remain largely unknown specifically in cases with male factor infertility. We examined whether PPI use was associated with detrimental effects on semen parameters in a large population of subfertile men. We retrospectively reviewed data from 12 257 subfertile men who had visited our fertility clinic from 2003 to 2013. Patients who reported using any PPIs for >3 months before semen sample collection were included; 7698 subfertile men taking no medication served as controls. Data were gathered on patient age, medication use, and conventional semen parameters; patients taking any known spermatotoxic medication were excluded. Linear mixed-effect regression models were used to test the effect of PPI use on semen parameters adjusting for age. A total of 248 patients (258 samples) used PPIs for at least 3 months before semen collection. In regression models, PPI use (either as the only medication or when used in combination with other nonspermatotoxic medications) was not associated with statistically significant changes in semen parameters. To our knowledge, this is the largest study to compare PPI use with semen parameters in subfertile men. Using PPIs was not associated with detrimental effects on semen quality in this retrospective study.
Sealing properties of mechanical seals for an axial flow blood pump.

Science.gov (United States)

Tomioka, J; Mori, T; Yamazaki, K; Koyanagi, H

1999-08-01

A miniature intraventricular axial flow blood pump for left ventricular support is under development. One of the key technologies required for such pumps is sealing of the motor shaft. In this study, to prevent blood backflow into the motor side, mechanical seals were developed and their sealing properties investigated. In the experimental apparatus, the mechanical seal separated the bovine blood on the chamber side from the cooling water on the motor side. A leakage of the blood was measured by inductively coupled plasma (ICP) light emission analysis. The rate of hemolysis was measured by the cyanmethemoglobin method. Frictional torque acting on the shaft was measured by a torque transducer. In the experiments, the rotational speed of the shaft was changed from 1,000 to 10,000 rpm, and the contact force of the seal faces was changed from 1.96 to 4.31 N. To estimate lubrication regimes, the Stribeck curve, a diagram of the coefficient of friction against the bearing characteristic G number, was drawn. The results of the experiments showed that both the leakage of blood and the rate of hemolysis were very small. The friction loss was also very small. The mechanical seal was operated in various lubrication regimes, from a fluid lubrication regime to a mixed lubrication regime.
Development of a rotary clap mechanism for positive-displacement rotary pumps: Kinematic analysis and working principle

International Nuclear Information System (INIS)

Shim, Sung Bo; Kim, Kyeong Uk; Park, Young Jun; Kim, Jong Mun

2015-01-01

A five-bar spatial mechanism named as a rotary clap mechanism is developed as a pumping device for positive displacement rotary pumps. The mechanism comprises a driving crank, a shaft link with two pins and two gears mounted on the middle and both ends, two rotors with jaws equally spaced along their circumferences, and two fixed internal gears. As the crank rotates, the gear pin-jointed to the crank rotates about the crank pin and at the same time rotates about the center of the fixed internal gears like a hypo-cyclic gear train. The gear-attached shaft link also rotates about the crank pin and about the fixed internal gears at the same time. This motion of the shaft link makes the pins rotate about the center of the fixed internal gears with a periodically varying radius. Therefore, two rotors driven by the pins rotate with different angular velocities. One rotor alternately leads and lags relative to the other rotor. These lead-lag motions between the two jaws of the rotors, which result in suction and discharge required for pumping, resemble hand clapping from which the mechanism was named. Construction and design parameters of the rotary clap mechanism are introduced, and kinematic analysis of this mechanism is performed. The relationships among design parameters, inherent constraints, and effects of design parameters on the is placement of mechanism are also presented.
The Toolbox of Proton Spin Physics in Historical Perspective

International Nuclear Information System (INIS)

Haeberli, Willy

2008-01-01

This paper was part of the general-interest session on lecture day, and is thus addressed to a general audience. A 50-year historic overview of the development of the tools of proton spin physics is presented: nuclear scattering, ion sources for polarized protons and deuterons based on atomic beam and optical pumping methods, and polarized gas targets
Arabidopsis type I proton-pumping pyrophosphatase expresses strongly in phloem, where it is required for pyrophosphate metabolism and photosynthate partitioning.

Science.gov (United States)

Pizzio, Gaston A; Paez-Valencia, Julio; Khadilkar, Aswad S; Regmi, Kamesh; Patron-Soberano, Araceli; Zhang, Shangji; Sanchez-Lares, Jonathan; Furstenau, Tara; Li, Jisheng; Sanchez-Gomez, Concepcion; Valencia-Mayoral, Pedro; Yadav, Umesh P; Ayre, Brian G; Gaxiola, Roberto A

2015-04-01

Phloem loading is a critical process in plant physiology. The potential of regulating the translocation of photoassimilates from source to sink tissues represents an opportunity to increase crop yield. Pyrophosphate homeostasis is crucial for normal phloem function in apoplasmic loaders. The involvement of Arabidopsis (Arabidopsis thaliana) type I proton-pumping pyrophosphatase (AVP1) in phloem loading was analyzed at genetic, histochemical, and physiological levels. A transcriptional AVP1 promoter::GUS fusion revealed phloem activity in source leaves. Ubiquitous AVP1 overexpression (35S::AVP1 cassette) enhanced shoot biomass, photoassimilate production and transport, rhizosphere acidification, and expression of sugar-induced root ion transporter genes (POTASSIUM TRANSPORTER2 [KUP2], NITRATE TRANSPORTER2.1 [NRT2.1], NRT2.4, and PHOSPHATE TRANSPORTER1.4 [PHT1.4]). Phloem-specific AVP1 overexpression (Commelina Yellow Mottle Virus promoter [pCOYMV]::AVP1) elicited similar phenotypes. By contrast, phloem-specific AVP1 knockdown (pCoYMV::RNAiAVP1) resulted in stunted seedlings in sucrose-deprived medium. We also present a promoter mutant avp1-2 (SALK046492) with a 70% reduction of expression that did not show severe growth impairment. Interestingly, AVP1 protein in this mutant is prominent in the phloem. Moreover, expression of an Escherichia coli-soluble pyrophosphatase in the phloem (pCoYMV::pyrophosphatase) of avp1-2 plants resulted in severe dwarf phenotype and abnormal leaf morphology. We conclude that the Proton-Pumping Pyrophosphatase AVP1 localized at the plasma membrane of the sieve element-companion cell complexes functions as a synthase, and that this activity is critical for the maintenance of pyrophosphate homeostasis required for phloem function. © 2015 American Society of Plant Biologists. All Rights Reserved.
Structure and operation of bacterial tripartite pumps.

Science.gov (United States)

Hinchliffe, Philip; Symmons, Martyn F; Hughes, Colin; Koronakis, Vassilis

2013-01-01

In bacteria such as Pseudomonas aeruginosa and Escherichia coli, tripartite membrane machineries, or pumps, determine the efflux of small noxious molecules, such as detergents, heavy metals, and antibiotics, and the export of large proteins including toxins. They are therefore influential in bacterial survival, particularly during infections caused by multidrug-resistant pathogens. In these tripartite pumps an inner membrane transporter, typically an ATPase or proton antiporter, binds and translocates export or efflux substrates. In cooperation with a periplasmic adaptor protein it recruits and opens a TolC family cell exit duct, which is anchored in the outer membrane and projects across the periplasmic space between inner and outer membranes. Assembled tripartite pumps thus span the entire bacterial cell envelope. We review the atomic structures of each of the three pump components and discuss how these have allowed high-resolution views of tripartite pump assembly, operation, and possible inhibition.
Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma.

Science.gov (United States)

Canitano, Andrea; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Federici, Cristina; Fais, Stefano

2016-07-01

Multiple Myeloma (MM) is the second most common hematological malignancy and is responsive to a limited number of drugs. Unfortunately, to date, despite the introduction of novel drugs, no relevant increase in survival rates has been obtained. Proton pump inhibitors (PPIs) have been shown to have significant antitumor action as single agents as well as in combination with chemotherapy. This study investigates the potential anti-tumor effectiveness of two PPIs, Lansoprazole and Omeprazole, against human MM cells. We found that Lansoprazole exerts straightforward efficacy against myeloma cells, even at suboptimal concentrations (50 µM), while Omeprazole has limited cytotoxic action. The Lansoprazole anti-MM effect was mostly mediated by a caspase-independent apoptotic-like cytotoxicity, with only a secondary anti-proliferative action. This study provides clear evidence supporting the use of Lansoprazole in the strive against MM with an efficacy proven much higher than current therapeutical approaches and without reported side effects. It is however conceivable that, consistent with the results obtained in other human tumors, Lansoprazole may well be combined with existing anti-myeloma therapies with the aim to improve the low level of efficacy of the current strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Overutilization of proton pump inhibitors: a review of cost-effectiveness and risk [corrected].

Science.gov (United States)

Heidelbaugh, Joel J; Goldberg, Kathleen L; Inadomi, John M

2009-03-01

Proton pump inhibitors (PPIs) are superior to histamine-2 receptor antagonists for the treatment of gastroesophageal reflux disease (GERD) and erosive esophagitis. Antisecretory therapy (AST), however, accounts for significant cost expenditure in the United States including over-the-counter and prescription formulations. Moreover, emerging data illustrate the potential risks associated with long-term PPI therapy including variations in bioavailability of common medications, vitamin B12 deficiency, Clostridium difficile-associated diarrhea, community-acquired pneumonia, and hip fracture. For these reasons, it is imperative to use the lowest dose of drug necessary to achieve desired therapeutic goals. This may entail the use of step-down, step-off, or on-demand PPI therapy for the treatment of GERD. In addition, PPIs are the most commonly used medications for stress ulcer prophylaxis (SUP), despite little evidence to support their use. Compounding this problem is evidence that patients erroneously administered SUP are often discharged on long-term PPI therapy. Pharmacy-driven step-down orders, limitation of the use of PPIs for SUP in non-ICU settings, and meticulous chart review to ensure that hospitalized patients are not discharged home on a PPI without an appropriate indication are interventions that can ensure proper PPI utilization with minimal of risk and optimization of cost-effectiveness.
Pump Application as Hydraulic Turbine – Pump as Turbine (PaT)

OpenAIRE

Rusovs, D

2009-01-01

The paper considers pump operation as hydraulic turbine with purpose to produce mechanical power from liquid flow. The Francis hydraulic turbine was selected for comparison with centrifugal pump in reverse operation. Turbine and centrifugal pump velocity triangles were considered with purpose to evaluate PaT efficiency. Shape of impeller blades for turbine and pumps was analysed. Specific speed calculation is carried out with purpose to obtain similarity in pump and turbine description. For ...
Strong-field dissociation of CS2+ via a pump/dump-like mechanism

Science.gov (United States)

Severt, T.; Zohrabi, M.; Betsch, K. J.; Ablikim, U.; Jochim, Bethany; Carnes, K. D.; Zeng, S.; Esry, B. D.; Ben-Itzhak, I.; Uhlíková, T.

2014-05-01

Laser-induced dissociation of the quasi-bound electronic ground state of CS2+ is investigated in intense laser pulses (pump/dump-like mechanism to explain this observed feature. Contrary to the conventional pump/dump control scheme, this process occurs within a single laser pulse, where the time delay is caused by the molecular structure. The process begins when the vibrational wavepacket in the electronic ground state of CS2+ is pumped into the electronic first excited state's continuum by a single photon. After a period of stretching at an energy above the potential barrier, the emission of a second photon is stimulated by the same laser pulse, most likely at the Condon point. Supported by the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy, Grants DE-FG02-86ER13491 and DE-FG02-09ER16115. TU supported by GACR and MetaCentrum.
A Benzimidazole Proton Pump Inhibitor Increases Growth and Tolerance to Salt Stress in Tomato

Directory of Open Access Journals (Sweden)

Michael J. Van Oosten

2017-07-01

Full Text Available Pre-treatment of tomato plants with micromolar concentrations of omeprazole (OP, a benzimidazole proton pump inhibitor in mammalian systems, improves plant growth in terms of fresh weight of shoot and roots by 49 and 55% and dry weight by 54 and 105% under salt stress conditions (200 mM NaCl, respectively. Assessment of gas exchange, ion distribution, and gene expression profile in different organs strongly indicates that OP interferes with key components of the stress adaptation machinery, including hormonal control of root development (improving length and branching, protection of the photosynthetic system (improving quantum yield of photosystem II and regulation of ion homeostasis (improving the K+:Na+ ratio in leaves and roots. To our knowledge OP is one of the few known molecules that at micromolar concentrations manifests a dual function as growth enhancer and salt stress protectant. Therefore, OP can be used as new inducer of stress tolerance to better understand molecular and physiological stress adaptation paths in plants and to design new products to improve crop performance under suboptimal growth conditions.Highlight: Omeprazole enhances growth of tomato and increases tolerance to salinity stress through alterations of gene expression and ion uptake and transport.
Excited state proton transfer in strongly enhanced GFP (sGFP2)

NARCIS (Netherlands)

van Oort, B.F.; ter Veer, M.J.T.; Groot, M.L.; van Stokkum, I.H.M.

2012-01-01

Proton transfer is an elementary process in biology. Green fluorescent protein (GFP) has served as an important model system to elucidate the mechanistic details of this reaction, because in GFP proton transfer can be induced by light absorption. We have used pump-dump-probe spectroscopy to study
Mosquitoes drink with a burst in reserve: explaining pumping behavior with a fluid mechanics model

Science.gov (United States)

Chatterjee, Souvick; Socha, Jake; Stremler, Mark

2014-11-01

Mosquitoes drink using a pair of in-line pumps in the head that draw liquid food through the proboscis. Experimental observations with synchrotron x-ray imaging indicate two modes of drinking: a predominantly occurring continuous mode, in which the cibarial and pharyngeal pumps expand cyclically at a constant phase difference, and an occasional, isolated burst mode, in which the pharyngeal pump expansion is 10 to 30 times larger than in the continuous mode. We have used a reduced order model of the fluid mechanics to hypothesize an explanation of this variation in drinking behavior. Our model results show that the continuous mode is more energetically efficient, whereas the burst mode creates a large pressure drop across the proboscis, which could potentially be used to clear blockages. Comparisons with pump knock-out configurations demonstrate different functional roles of the pumps in mosquito feeding. This material is based upon work supported by the NSF under Grant No. #0938047.

Long-term proton pump inhibitor therapy and falls and fractures in elderly women: a prospective cohort study.

Science.gov (United States)

Lewis, Joshua R; Barre, Deka; Zhu, Kun; Ivey, Kerry L; Lim, Ee Mun; Hughes, Jeff; Prince, Richard L

2014-11-01

Proton pump inhibitors (PPIs) are widely used in the elderly. Recent studies have suggested that long-term PPI therapy is associated with fractures in the elderly, however the mechanism remains unknown. We investigated the association between long-term PPI therapy ≥1 year and fracture risk factors including bone structure, falls, and balance-related function in a post hoc analysis of a longitudinal population-based prospective cohort of elderly postmenopausal women and replicated the findings in a second prospective study of falling in elderly postmenopausal women. Long-term PPI therapy was associated with increased risk of falls and fracture-related hospitalizations; adjusted odds ratio (AOR) 2.17; 95% CI, 1.25-3.77; p = 0.006 and 1.95; 95% CI, 1.20-3.16; p = 0.007, respectively. In the replication study, long-term PPI use was associated with an increased risk of self-reported falling; AOR, 1.51; 95% CI, 1.00-2.27; p = 0.049. No association of long-term PPI therapy with bone structure was observed; however, questionnaire-assessed falls-associated metrics such as limiting outdoor activity (p = 0.002) and indoor activity (p = 0.001) due to fear of falling, dizziness (p risk in subjects on long-term PPI therapy. This increase in fracture risk in elderly women, already at high risk of fracture, appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long-term PPI therapy. © 2014 American Society for Bone and Mineral Research.
Transient Resonance Raman Spectroscopy of a Light-Driven Sodium-Ion-Pump Rhodopsin from Indibacter alkaliphilus.

Science.gov (United States)

Kajimoto, Kousuke; Kikukawa, Takashi; Nakashima, Hiroki; Yamaryo, Haruki; Saito, Yuta; Fujisawa, Tomotsumi; Demura, Makoto; Unno, Masashi

2017-05-04

Sodium-ion-pump rhodopsin (NaR) is a microbial rhodopsin that transports Na + during its photocycle. Here we explore the photocycle mechanism of NaR from Indibacter alkaliphilus with transient absorption and transient resonance Raman spectroscopy. The transient absorption data indicate that the photocycle of NaR is K (545 nm) → L (490 nm)/M (420 nm) → O 1 (590 nm) → O 2 (560 nm) → NaR, where the L and M are formed as equilibrium states. The presence of K, L, M, and O intermediates was confirmed by the resonance Raman spectra with 442 and 532 nm excitation. The main component of the transient resonance Raman spectra was due to L which contains a 13-cis retinal protonated Schiff base. The presence of an enhanced hydrogen out-of-plane band as well as its sensitivity to the H/D exchange indicate that the retinal chromophore is distorted near the Schiff base region in L. Moreover, the retinal Schiff base of the L state forms a hydrogen bond that is stronger than that of the dark state. These observations are consistent with a Na + pumping mechanism that involves a proton transfer from the retinal Schiff base to a key aspartate residue (Asp116 in Krokinobacter eikastus rhodopsin 2) in the L/M states.
Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors.

Science.gov (United States)

Yu, Man; Lee, Carol; Wang, Marina; Tannock, Ian F

2015-10-01

Cellular causes of resistance and limited drug distribution within solid tumors limit therapeutic efficacy of anticancer drugs. Acidic endosomes in cancer cells mediate autophagy, which facilitates survival of stressed cells, and may contribute to drug resistance. Basic drugs (e.g. doxorubicin) are sequestered in acidic endosomes, thereby diverting drugs from their target DNA and decreasing penetration to distal cells. Proton pump inhibitors (PPIs) may raise endosomal pH, with potential to improve drug efficacy and distribution in solid tumors. We determined the effects of the PPI lansoprazole to modify the activity of doxorubicin. To gain insight into its mechanisms, we studied the effects of lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and of biomarkers reflecting its activity, using in vitro and murine models. Lansoprazole showed concentration-dependent effects to raise endosomal pH and to inhibit endosomal sequestration of doxorubicin in cultured tumor cells. Lansoprazole was not toxic to cancer cells but potentiated the cytotoxicity of doxorubicin and enhanced its penetration through multilayered cell cultures. In solid tumors, lansoprazole improved the distribution of doxorubicin but also increased expression of biomarkers of drug activity throughout the tumor. Combined treatment with lansoprazole and doxorubicin was more effective in delaying tumor growth as compared to either agent alone. Together, lansoprazole enhances the therapeutic effects of doxorubicin both by improving its distribution and increasing its activity in solid tumors. Use of PPIs to improve drug distribution and to inhibit autophagy represents a promising strategy to enhance the effectiveness of anticancer drugs in solid tumors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
Baryon production in proton-proton collisions

International Nuclear Information System (INIS)

Liu, F.M.; Werner, K.

2002-01-01

Motivated by the recent rapidity spectra of baryons and antibaryons in pp collisions at 158 GeV and the Ω-bar/Ω ratio discussion, we reviewed string formation mechanism and some string models. This investigation told us how color strings are formed in ultrarelativistic proton-proton collisions
The effect of endoscopic fundoplication and proton pump inhibitors on baseline impedance and heartburn severity in GERD patients.

Science.gov (United States)

Rinsma, N F; Farré, R; Bouvy, N D; Masclee, A A M; Conchillo, J M

2015-02-01

Antireflux therapy may lead to recovery of impaired mucosal integrity in gastro-esophageal reflux disease (GERD) patients as reflected by an increase in baseline impedance. The study objective was to evaluate the effect of endoscopic fundoplication and proton pump inhibitor (PPI) PPI therapy on baseline impedance and heartburn severity in GERD patients. Forty-seven GERD patients randomized to endoscopic fundoplication (n = 32) or PPI therapy (n = 15), and 29 healthy controls were included. Before randomization and 6 months after treatment, baseline impedance was obtained during 24-h pH-impedance monitoring. Heartburn severity was evaluated using the GERD-HRQL questionnaire. Before treatment, baseline impedance in GERD patients was lower than in healthy controls (p heartburn severity indicates that other factors may contribute to heartburn perception in GERD. © 2014 John Wiley & Sons Ltd.
Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study

DEFF Research Database (Denmark)

Charlot, Mette; Grove, Erik; Hansen, Peter Riis

2011-01-01

: All aspirin treated patients surviving 30 days after a first myocardial infarction from 1997 to 2006, with follow-up for one year. Patients treated with clopidogrel were excluded. MAIN OUTCOME MEASURES: The risk of the combined end point of cardiovascular death, myocardial infarction, or stroke...... associated with use of proton pump inhibitors was analysed using Kaplan-Meier analysis, Cox proportional hazard models, and propensity score matched Cox proportional hazard models. Results 3366 of 19 925 (16.9%) aspirin treated patients experienced recurrent myocardial infarction, stroke, or cardiovascular...
Supply of clean water to the bearings and mechanical seals of the backup pumps

International Nuclear Information System (INIS)

Jolas, C.

1997-01-01

The purpose of the backup pumps is to cool the primary circuit and pressurised water reactor containment in the case of a primary cooler loss accident. The water taken in by these pumps in the case of accident is loaded with solid particles. In order to ensure correct operation of the bearings and mechanical seals of these machines, they must be supplied with clean water. In other words, the solid particles must be removed from the water intake. Manufacturers generally use cyclonic separators to achieve this. (author)
Proton gradients and proton-dependent transport processes in the chloroplast

Directory of Open Access Journals (Sweden)

Ricarda eHöhner

2016-02-01

Full Text Available Proton gradients are fundamental to chloroplast function. Across thylakoid membranes, the light induced proton gradient is essential for ATP synthesis. As a result of proton pumping into the thylakoid lumen, an alkaline stromal pH develops, which is required for full activation of pH-dependent Calvin Benson cycle enzymes. This implies that a pH gradient between the cytosol (pH 7 and the stroma (pH 8 is established upon illumination. To maintain this pH gradient chloroplasts actively extrude protons. More than 30 years ago it was already established that these proton fluxes are electrically counterbalanced by Mg2+, K+ or Cl- fluxes, but only recently the first transport systems that regulate the pH gradient were identified. Notably several (Na+,K+/H+ antiporter systems where identified, that play a role in pH gradient regulation, ion homeostasis, osmoregulation, or coupling of secondary active transport. The established pH gradients are important to drive uptake of essential ions and solutes, but not many transporters involved have been identified to date. In this mini review we summarize the current status in the field and the open questions that need to be addressed in order to understand how pH gradients are maintained, how this is interconnected with other transport processes and what this means for chloroplast function.
Time esophageal pH < 4 overestimates the prevalence of pathologic esophageal reflux in subjects with gastroesophageal reflux disease treated with proton pump inhibitors

Directory of Open Access Journals (Sweden)

Sloan Sheldon

2008-05-01

Full Text Available Abstract Background A Stanford University study reported that in asymptomatic GERD patients who were being treated with a proton pump inhibitor (PPI, 50% had pathologic esophageal acid exposure. Aim We considered the possibility that the high prevalence of pathologic esophageal reflux might simply have resulted from calculating acidity as time pH Methods We calculated integrated acidity and time pH Results The prevalence of pathologic 24-hour esophageal reflux in both studies was significantly higher when measured as time pH Conclusion In GERD subjects treated with a PPI, measuring time esophageal pH
Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump's activity

Directory of Open Access Journals (Sweden)

T.I. Omotayo

2015-04-01

Full Text Available The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe2+-mediated in vitro oxidative stress model. The results show that Fe2+ inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe2+ inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe2+ may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe2+ and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump.
Human Aorta Is a Passive Pump

Science.gov (United States)

Pahlevan, Niema; Gharib, Morteza

2012-11-01

Impedance pump is a simple valveless pumping mechanism that operates based on the principles of wave propagation and reflection. It has been shown in a zebrafish that a similar mechanism is responsible for the pumping action in the embryonic heart during early stages before valve formation. Recent studies suggest that the cardiovascular system is designed to take advantage of wave propagation and reflection phenomena in the arterial network. Our aim in this study was to examine if the human aorta is a passive pump working like an impedance pump. A hydraulic model with different compliant models of artificial aorta was used for series of in-vitro experiments. The hydraulic model includes a piston pump that generates the waves. Our result indicates that wave propagation and reflection can create pumping mechanism in a compliant aorta. Similar to an impedance pump, the net flow and the flow direction depends on the frequency of the waves, compliance of the aorta, and the piston stroke.
The direction of water transport on Mars: A possible pumping mechanism

Science.gov (United States)

James, P. B.

1987-01-01

It is suggested that an atmospheric pumping mechanism might be at work in which water is preferentially transported into the north by a mass outflow wind (due to sublimation from polar cap) that is stronger during southern spring than it is during northern spring. The mechanism is provided by the asymmetric seasonal temperature distribution produced by the eccentric martial orbit and by the associated seasonal asymmetry in the carbon dioxide cycle. The alternating condensation and sublimation of CO2 at the poles produces condensation winds which, in turn, contribute to the meridional transport of water vapor.
Leak Mitigation in Mechanically Pumped Fluid Loops for Long Duration Space Missions

Science.gov (United States)

Miller, Jennifer R.; Birur, Gajanana; Bame, David; Mastropietro, A. J.; Bhandari, Pradeep; Lee, Darlene; Karlmann, Paul; Liu, Yuanming

2013-01-01

Mechanically pumped fluid loops (MPFLs) are increasingly considered for spacecraft thermal control. A concern for long duration space missions is the leak of fluid leading to performance degradation or potential loop failure. An understanding of leak rate through analysis, as well as destructive and non-destructive testing, provides a verifiable means to quantify leak rates. The system can be appropriately designed to maintain safe operating pressures and temperatures throughout the mission. Two MPFLs on the Mars Science Laboratory Spacecraft, launched November 26, 2011, maintain the temperature of sensitive electronics and science instruments within a -40 deg C to 50 deg C range during launch, cruise, and Mars surface operations. With over 100 meters of complex tubing, fittings, joints, flex lines, and pumps, the system must maintain a minimum pressure through all phases of the mission to provide appropriate performance. This paper describes the process of design, qualification, test, verification, and validation of the components and assemblies employed to minimize risks associated with excessive fluid leaks from pumped fluid loop systems.
The Mechanism of $\\beta$-Delayed Two-Proton Emission

CERN Multimedia

2002-01-01

The nucleus $^{31}$Ar seems to be the most prolific ${\\beta}$-2p precursor known to date and is at the same time the one with the largest production yields at ISOLDE, where the most sensitive experiments can be done. Our purpose with this experiment is to study the ${\\beta}$-2p branches in detail, search for ${\\beta}$-3p events, place them in the decay scheme and obtain information on the decay mechanism for ${\\beta}$-2p via the energy distribution and the angular correlation between the two protons. As a by product we shall also resolve existing inconsistencies in the level scheme.\\\\ \\\\ The nucleus $^{31}$Ar, produced in a cold plasma ion source unit by the impact of a 1 GeV proton beam of 0.5 Hz frequency, had an average yield over one week of 1.5 $^{31}$Ar atoms/s. The beam passed through the central hole of an annular Si detector ($\\Omega$ = 4.3~\\%) and stopped in a thin carbon foil tilted 45$^o$ with respect to the beam direction. A 70~\\% coaxial HPGe-detector ($\\Omega$~=~7.4~\\%) was located opposite to ...
Mechanisms of proton conductance in polymer electrolyte membranes

DEFF Research Database (Denmark)

Eikerling, M.; Kornyshev, A. A.; Kuznetsov, A. M.

2001-01-01

We provide a phenomenological description of proton conductance in polymer electrolyte membranes, based on contemporary views of proton transfer processes in condensed media and a model for heterogeneous polymer electrolyte membrane structure. The description combines the proton transfer events...... in a single pore with the total pore-network performance and, thereby, relates structural and kinetic characteristics of the membrane. The theory addresses specific experimentally studied issues such as the effect of the density of proton localization sites (equivalent weight) of the membrane material...
Electrostatic coupling of ion pumps.

Science.gov (United States)

Nieto-Frausto, J; Lüger, P; Apell, H J

1992-01-01

In this paper the electrostatic interactions between membrane-embedded ion-pumps and their consequences for the kinetics of pump-mediated transport processes have been examined. We show that the time course of an intrinsically monomolecular transport reaction can become distinctly nonexponential, if the reaction is associated with charge translocation and takes place in an aggregate of pump molecules. First we consider the electrostatic coupling of a single dimer of ion-pumps embedded in the membrane. Then we apply the treatment to the kinetic analysis of light-driven proton transport by bacteriorhodopsin which forms two-dimensional hexagonal lattices. Finally, for the case of nonordered molecules, we also consider a model in which the pumps are randomly distributed over the nodes of a lattice. Here the average distance is equal to that deduced experimentally and the elemental size of the lattice is the effective diameter of one single pump. This latter model is applied to an aggregate of membrane-embedded Na, K- and Ca-pumps. In all these cases the electrostatic potential considered is the exact solution calculated from the method of electrical images for a plane membrane of finite thickness immersed in an infinite aqueous solution environment. The distributions of charges (ions or charged binding sites) are considered homogeneous or discrete in the membrane and/or in the external solution. In the case of discrete distributions we compare the results from a mean field approximation and a stochastic simulation.
BIOMATERIALS FOR ROTARY BLOOD PUMPS

NARCIS (Netherlands)

VANOEVEREN, W

Rotary blood pumps are used for cardiac assist and cardiopulmonary support since mechanical blood damage is less than with conventional roller pumps. The high shear rate in the rotary pump and the reduced anticoagulation of the patient during prolonged pumping enforces high demands on the
Study of Hydrogen Pumping through Condensed Argon in Cryogenic pump

International Nuclear Information System (INIS)

Jadeja, K A; Bhatt, S B

2012-01-01

In ultra high vacuum (UHV) range, hydrogen is a dominant residual gas in vacuum chamber. Hydrogen, being light gas, pumping of hydrogen in this vacuum range is limited with widely used UHV pumps, viz. turbo molecular pump and cryogenic pump. Pre condensed argon layers in cryogenic pump create porous structure on the surface of the pump, which traps hydrogen gas at a temperature less than 20° K. Additional argon gas injection in the cryogenic pump, at lowest temperature, generates multiple layers of condensed argon as a porous frost with 10 to 100 A° diameters pores, which increase the pumping capacity of hydrogen gas. This pumping mechanism of hydrogen is more effective, to pump more hydrogen gas in UHV range applicable in accelerator, space simulation etc. and where hydrogen is used as fuel gas like tokamak. For this experiment, the cryogenic pump with a closed loop refrigerator using helium gas is used to produce the minimum cryogenic temperature as ∼ 14° K. In this paper, effect of cryosorption of hydrogen is presented with different levels of argon gas and hydrogen gas in cryogenic pump chamber.
The mechanism of coupling between oxido-reduction and proton translocation in respiratory chain enzymes.

Science.gov (United States)

Papa, Sergio; Capitanio, Giuseppe; Papa, Francesco

2018-02-01

The respiratory chain of mitochondria and bacteria is made up of a set of membrane-associated enzyme complexes which catalyse sequential, stepwise transfer of reducing equivalents from substrates to oxygen and convert redox energy into a transmembrane protonmotive force (PMF) by proton translocation from a negative (N) to a positive (P) aqueous phase separated by the coupling membrane. There are three basic mechanisms by which a membrane-associated redox enzyme can generate a PMF. These are membrane anisotropic arrangement of the primary redox catalysis with: (i) vectorial electron transfer by redox metal centres from the P to the N side of the membrane; (ii) hydrogen transfer by movement of quinones across the membrane, from a reduction site at the N side to an oxidation site at the P side; (iii) a different type of mechanism based on co-operative allosteric linkage between electron transfer at the metal redox centres and transmembrane electrogenic proton translocation by apoproteins. The results of advanced experimental and theoretical analyses and in particular X-ray crystallography show that these three mechanisms contribute differently to the protonmotive activity of cytochrome c oxidase, ubiquinone-cytochrome c oxidoreductase and NADH-ubiquinone oxidoreductase of the respiratory chain. This review considers the main features, recent experimental advances and still unresolved problems in the molecular/atomic mechanism of coupling between the transfer of reducing equivalents and proton translocation in these three protonmotive redox complexes. © 2017 Cambridge Philosophical Society.
Polarized proton target with horizontal spin orientation

International Nuclear Information System (INIS)

Bunyatova, Eh.I.; Kiselev, Yu.F.; Kozlenko, N.G.

1988-01-01

Proton target, the polarization vector of which may be arbitrary oriented in horizontal plane relatively to the beam, is developed and tested. 70% value of polarization is obtained. 0.6 K temperature is acquired through 3 He pumping out continuous cycle. 1.2-propylene glycol - Cr(V) was used as working medium. Magnetic system is made in the form of Helmholtz sperconducting coils with working curren close to critical one. Target polarization is measured by NMR technique using original system of proton signal processing

Mechanical seals qualification procedure of the main pumps of nuclear power plants in France

International Nuclear Information System (INIS)

Buchdahl, D.; Martin, R.; Girault, J.M.

1992-12-01

Many important pumps in the nuclear power plants are equipped with mechanical seals. The good behaviour and reliability of mechanical seals depend specially on the quality and the stability of an interface of several microns. Peripheral speed reaches 50 m/s and pressure 5 MPa, shaft diameter may be 200 mm. Any failure of the mechanical seals may stop the production of electricity or may compromise nuclear safety. As far back as 1970, EDF has conducted qualification actions for the most important mechanical seals in terms of availability and safety. A qualification of mechanical seals needs three steps: - constructor test (tuning) at normal conditions, -qualification test on test rig at EDF/DER (semi-industrial) at normal, exceptional and incidental conditions lasting about 1500 h, - industrial qualification test in nuclear power station over one year. Several supplying sources are absolutely necessary. Any pump may receive mechanical seals from at least two different suppliers. A compromise had to be found to restrict the suppliers' number down to three. This choice concerned three high technology suppliers. A consistent modification procedure had been developed (references file procedure). For each power plant series, about ten types of mechanical seals are concerned. The selection criteria are the higher loads factors P, Vg or the safety related importance. This expensive approach is useful for EDF, many functional failures have been detected before the serial mechanical seals installation in the power plants. (authors). 1 annexe
Experiences in design up-gradation of mechanical seal cooling scheme of Dhruva PHT pumps

International Nuclear Information System (INIS)

Balakrishnan, K.T.P.

2002-01-01

Full text: Dhruva is a natural uranium fuelled high flux research reactor. Heavy water is used as coolant, moderator and reflector. Heat from the heavy water coolant is removed in heat exchangers by demineralised water. The heavy water coolant is re-circulated between the reactor core and the heat exchangers in three separate loops by three main coolant pumps (MCPs). The MCPs are high capacity centrifugal pumps and are rated for continuous service. The mechanical seal of the pump prevents leakage of the process fluid, which is heavy water, through the pump shaft. Continuous operation of the pump results in the heating up of the seal and necessitates sustained cooling. An integral cooling provision is made by tapping a 15 NB line from the discharge volute of the pump and feeding the process fluid itself as coolant to the seal. A non-indicating type flow-sensing device monitors flow through this line. Limiting values of flow are set and annunciated by a pair of magnetic reed type relays. This cooling line was a built in feature of the pumps as supplied by the manufacturer. This arrangement had the following inherent limitations: 1. There was no on line indication of the coolant flow. 2. The reed type magnetic relays initiated pump trips by spurious actuation, resulting in the interruption of reactor operation. Servicing a faulty flow switch involved lengthy procedures and necessitated draining, filling and venting of the pump. This entailed extended plant outages. Close proximity of these flow switches to a highly radioactive piping element imposed severe restrictions on the planned maintenance activity on them. Efforts were made to provide a suitable alternate cooling and flow measurement scheme to overcome the above-mentioned limitations. After evaluating the relative merits and demerits of several schemes, a turbine type flow sensor, on a modified cooling line was selected as the most suitable alternative. The alternate seal-cooling scheme was implemented for all
Experiences in design up-gradation of mechanical seal cooling scheme of Dhruva PHT pumps

International Nuclear Information System (INIS)

Balakrishnan, K.T.P.; Bharathan, R.

2002-01-01

Full text: Dhruva is a natural uranium fuelled high flux research reactor. Heavy water is used as coolant, moderator and reflector. Heat from the heavy water coolant is removed in heat exchangers by demineralised water. The heavy water coolant is re-circulated between the reactor core and the heat exchangers in three separate loops by three main coolant pumps (MCPs). The MCPs are high capacity centrifugal pumps and are rated for continuous service. The mechanical seal of the pump prevents leakage of the process fluid, which is heavy water, through the pump shaft. Continuous operation of the pump results in the heating up of the seal and necessitates sustained cooling. An integral cooling provision is made by tapping a 15 NB line from the discharge volute of the pump and feeding the process fluid itself as coolant to the seal. A non-indicating type flow-sensing device monitors flow through this line. Limiting values of flow are set and annunciated by a pair of magnetic reed type relays. This cooling line was a built in feature of the pumps as supplied by the manufacturer. This arrangement had the following inherent limitations : 1. There was no on line indication of the coolant flow. 2. The reed type magnetic relays initiated pump trips by spurious actuation, resulting in the interruption of reactor operation. Servicing a faulty flow switch involved lengthy procedures and necessitated draining, filling and venting of the pump. This entailed extended plant outages. Close proximity of these flow switches to a highly radioactive piping element imposed severe restrictions on the planned maintenance activity on them. Efforts were made to provide a suitable alternate cooling and flow measurement scheme to overcome the above-mentioned limitations. After evaluating the relative merits and demerits of several schemes, a turbine type flow sensor, on a modified cooling line was selected as the most suitable alternative. The alternate seal-cooling scheme was implemented for all
Stimulation by ATP of proinsulin to insulin conversion in isolated rat pancreatic islet secretory granules. Association with the ATP-dependent proton pump

International Nuclear Information System (INIS)

Rhodes, C.J.; Lucas, C.A.; Mutkoski, R.L.; Orci, L.; Halban, P.A.

1987-01-01

Isolated rat pancreatic islets were pulse-labeled for 5 min with [ 3 H]leucine then chased for 25 min, during which time endogenously labeled [ 3 H]proinsulin becomes predominantly compartmented in immature secretory granules. The islets were then homogenized in isotonic sucrose (pH 7.4) and a beta-granule preparation obtained by differential centrifugation and discontinuous sucrose gradient ultracentrifugation. This preparation was enriched 8-fold in beta-granules. Aside from contamination with mitochondria and a limited number of lysosomes, the beta-granule preparation was essentially free of any other organelles involved in proinsulin synthesis and packaging (i.e. microsomal elements and, more particularly, Golgi complex). Conversion of endogenously labeled [ 3 H]proinsulin was followed in this beta-granule fraction for up to 2 h at 37 degrees C in a buffer (pH 7.3) that mimicked the cationic constituents of B-cell cytosol, during which time 92% of the beta-granules remained intact. Proinsulin conversion was analyzed by high performance liquid chromatography. The rate of proinsulin conversion to insulin was stimulated by 2.2 +/- 0.1-fold (n = 6) (at a 60-min incubation) in the presence of ATP (2 mM) and an ATP regenerating system compared to beta-granule preparations incubated without ATP. This ATP stimulation was abolished in the presence of beta-granule proton pump ATPase inhibitors (tributyltin, 2.5 microM, or 1,3-dicyclohexylcarbodiimide, 50 microM). Inhibitors of mitochondrial proton pump ATPases had no effect on the ATP stimulation of proinsulin conversion. When granules were incubated in a more acidic buffer, proinsulin conversion was increased relative to that at pH 7.3. At pH 5.5, ATP no longer stimulated conversion, and tributyltin and 1,3-dicyclohexylcarbodiimide had no effect
High pressure liquid gas pump

Science.gov (United States)

Acres, R. L.

1972-01-01

Design and development of two types of pumps for handling liquefied gases are discussed. One pump uses mechanical valve shift and other uses pneumatic valve shift. Illustrations of pumps are provided and detailed description of operation is included.
Proton scattering from Li isotopes in the context of the Glauber theory. nuclear structure and interaction mechanisms

International Nuclear Information System (INIS)

Ibrayeva, E.T.; Prmantayeva, B. A.; Kuterbekov, K. A.; Temerbayev, A. A.; Tleulessova, I. K.; Zhigalova, A.

2012-01-01

The purpose of the present work is studying the structure of various isotopes of lithium 6 , 7 , 8 , 9 Li and the mechanism of their interaction with protons in the processes of elastic scattering. Differential cross sections and analyzing powers for elastic proton scattering from nuclei of Li are calculated in the context of the Glauber diffraction theory. Comparison of the result of calculations with the experimental data has allowed to draw conclusions on the structure of the given nuclei and their interaction mechanisms. (Authors)
The influence of hospital drug formulary policies on the prescribing patterns of proton pump inhibitors in primary care

DEFF Research Database (Denmark)

Larsen, Michael Due; Schou, Mette; Kristiansen, Anja Sparre

2014-01-01

decreased from 33.5 to 9.4 %, corresponding to a risk ratio of 0.28. In primary care after discharge, 13.4 % of esomeprazole use was initiated in the hospital, and this was 8.4 % for PPIs in general. After the change of hospital drug policy, this decreased to 6.5 % for esomeprazole and increased......AIM: This study had two aims: Firstly, to describe how prescriptions for proton pump inhibitor (PPI) in primary care were influenced by a change of the hospital drug policy, and secondly, to describe if a large discount on an expensive PPI (esomeprazole) to a hospital would influence prescribing...... policy on prescribings in primary care was measured by the likelihood of having a high-cost PPI prescribed before and after change of drug policy. RESULTS: In total, 9,341 hospital stays in 2009 and 2010 were included. The probability of a patient to be prescribed an expensive PPI after discharge...
Proton-pump inhibitors for prevention of upper gastrointestinal bleeding in patients undergoing dialysis.

Science.gov (United States)

Song, Young Rim; Kim, Hyung Jik; Kim, Jwa-Kyung; Kim, Sung Gyun; Kim, Sung Eun

2015-04-28

To investigate the preventive effects of low-dose proton-pump inhibitors (PPIs) for upper gastrointestinal bleeding (UGIB) in end-stage renal disease. This was a retrospective cohort study that reviewed 544 patients with end-stage renal disease who started dialysis at our center between 2005 and 2013. We examined the incidence of UGIB in 175 patients treated with low-dose PPIs and 369 patients not treated with PPIs (control group). During the study period, 41 patients developed UGIB, a rate of 14.4/1000 person-years. The mean time between the start of dialysis and UGIB events was 26.3 ± 29.6 mo. Bleeding occurred in only two patients in the PPI group (2.5/1000 person-years) and in 39 patients in the control group (19.2/1000 person-years). Kaplan-Meier analysis of cumulative non-bleeding survival showed that the probability of UGIB was significantly lower in the PPI group than in the control group (log-rank test, P < 0.001). Univariate analysis showed that coronary artery disease, PPI use, anti-coagulation, and anti-platelet therapy were associated with UGIB. After adjustments for the potential factors influencing risk of UGIB, PPI use was shown to be significantly beneficial in reducing UGIB compared to the control group (HR = 13.7, 95%CI: 1.8-101.6; P = 0.011). The use of low-dose PPIs in patients with end-stage renal disease is associated with a low frequency of UGIB.
[Adherence with proton pump inhibitor therapy, by continuously taking nonsteroidal anti-inflammatory drugs].

Science.gov (United States)

Pimanov, S I; Makarenko, E V; Dikareva, E A

2015-01-01

To estimate the impact of adherence with proton pump inhibitor (PPI) therapy on the incidence of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy (NSAID gastropathy) in patients with rheumatoid arthritis (RA). PPI pharmacotherapy adherence was estimated using the Medication Adherence Questionnaire (MAQ) in 92 patients with RA, including 32 patients did not take a PPI and 60 used a PPI. The groups were matched for age, disease duration, and used NSAIDs. All those asked underwent video esophagogastroduodenoscopy. According to the data of MAQ survey, low, moderate, and high adherence subgroups could be identified among the patients treated with a PPI. NSAID gastropathy was detected in 43.8% of the patients taking no PPI, in 50% of those with low PPI treatment adherence, in 12.5% with moderate adherence, and in 4.5% with high adherence. In the patients with low adherence to PPI therapy, NSAID gastropathy was recorded 11 times more frequently than in those with high adherence (c2 = 7.77; p = 0.005). This condition occurred in 28.6% of the patients taking NSAID without preventively using a PPI in the absence of risk factors for NSAID gastropathy. Only 36.7% patients who had been recommended to use a PPI for the prevention of NSAID gastropathy strictly observed their doctor's directions. Low PPI pharmacotherapy adherence may serve as an additional risk factor for NSAID gastropathy in patients in whom preventive antisecretory therapy used in combination with NSAID is indicated.
Proton pump inhibitors suppress iNOS-dependent DNA damage in Barrett's esophagus by increasing Mn-SOD expression

Energy Technology Data Exchange (ETDEWEB)

Thanan, Raynoo [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 (Japan); Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 (Japan); Ma, Ning [Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie 513-0293 (Japan); Iijima, Katsunori; Abe, Yasuhiko; Koike, Tomoyuki; Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Hospital, Sendai, Miyaki 980-8574 (Japan); Pinlaor, Somchai [Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 (Thailand); Hiraku, Yusuke; Oikawa, Shinji; Murata, Mariko [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 (Japan); Kawanishi, Shosuke, E-mail: kawanisi@suzuka-u.ac.jp [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 (Japan)

2012-05-04

Highlights: Black-Right-Pointing-Pointer Inflammation by Barrett's esophagus (BE) is a risk factor of its adenocarcinoma (BEA). Black-Right-Pointing-Pointer 8-Nitroguanine and 8-oxodG are inflammation-related DNA lesions. Black-Right-Pointing-Pointer DNA lesions and iNOS expression were higher in the order, BEA > BE > normal tissues. Black-Right-Pointing-Pointer Proton pump inhibitors suppress DNA damage by increasing Mn-SOD via Nrf2 activation. Black-Right-Pointing-Pointer DNA lesions can be useful biomarkers to predict risk of BEA in BE patients. -- Abstract: Barrett's esophagus (BE), an inflammatory disease, is a risk factor for Barrett's esophageal adenocarcinoma (BEA). Treatment of BE patients with proton pump inhibitors (PPIs) is expected to reduce the risk of BEA. We performed an immunohistochemical study to examine the formation of nitrative and oxidative DNA lesions, 8-nitroguanine and 8-oxo-7,8-dihydro-2 Prime -deoxygaunosine (8-oxodG), in normal esophageal, BE with pre- and post-treatment by PPIs and BEA tissues. We also observed the expression of an oxidant-generating enzyme (iNOS) and its transcription factor NF-{kappa}B, an antioxidant enzyme (Mn-SOD), its transcription factor (Nrf2) and an Nrf2 inhibitor (Keap1). The immunoreactivity of DNA lesions was significantly higher in the order of BEA > BE > normal tissues. iNOS expression was significantly higher in the order of BEA > BE > normal tissues, while Mn-SOD expression was significantly lower in the order of BEA < BE < normal tissues. Interestingly, Mn-SOD expression and the nuclear localization of Nrf2 were significantly increased, and the formation of DNA lesions was significantly decreased in BE tissues after PPIs treatment for 3-6 months. Keap1 and iNOS expression was not significantly changed by the PPIs treatment in BE tissues. These results indicate that 8-nitroguanine and 8-oxodG play a role in BE-derived BEA. Additionally, PPIs treatment may trigger the activation and
Effect of protonation on the mechanism of phosphate monoester hydrolysis and comparison with the hydrolysis of nucleoside triphosphate in biomolecular motors.

Science.gov (United States)

Hassan, Hammad Ali; Rani, Sadaf; Fatima, Tabeer; Kiani, Farooq Ahmad; Fischer, Stefan

2017-11-01

Hydrolysis of phosphate groups is a crucial reaction in living cells. It involves the breaking of two strong bonds, i.e. the O a H bond of the attacking water molecule, and the PO l bond of the substrate (O a and O l stand for attacking and leaving oxygen atoms). Mechanism of the hydrolysis reaction can proceed either by a concurrent or a sequential mechanism. In the concurrent mechanism, the breaking of O a H and PO l bonds occurs simultaneously, whereas in the sequential mechanism, the O a H and PO l bonds break at different stages of the reaction. To understand how protonation affects the mechanism of hydrolysis of phosphate monoester, we have studied the mechanism of hydrolysis of protonated and deprotonated phosphate monoester at M06-2X/6-311+G**//M06-2X/6-31+G*+ZPE level of theory (where ZPE stands for zero point energy). Our calculations show that in both protonated and deprotonated cases, the breaking of the water O a H bond occurs before the breaking of the PO l bond. Because the two events are not separated by a stable intermediate, the mechanism can be categorized as semi-concurrent. The overall energy barrier is 41kcalmol -1 in the unprotonated case. Most (5/6th) of this is due to the initial breaking of the water O a H bond. This component is lowered from 34 to 25kcalmol -1 by adding one proton to the phosphate. The rest of the overall energy barrier comes from the subsequent breaking of the PO l bond and is not sensitive to protonation. This is consistent with previous findings about the effect of triphosphate protonation on the hydrolysis, where the equivalent protonation (on the γ-phosphate) was seen to lower the barrier of breaking the water O a H bond and to have little effect on the PO l bond breaking. Hydrolysis pathways of phosphate monoester with initial breaking of the PO l bond could not be found here. This is because the leaving group in phosphate monoester cannot be protonated, unlike in triphosphate hydrolysis, where protonation of the �
Celecoxib versus a non-selective NSAID plus proton-pump inhibitor: what are the considerations?.

Science.gov (United States)

Chen, Judy T; Pucino, Frank; Resman-Targoff, Beth H

2006-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are extensively used worldwide. However, associated adverse gastrointestinal effects (NSAID gastropathy) such as bleeding, perforation and obstruction result in considerable morbidity, mortality, and expense. Although it is essential to employ gastroprotective strategies to minimize these complications in patients at risk, controversy remains on whether celecoxib alone or a non-selective NSAID in conjunction with a proton-pump inhibitor (PPI) is a superior choice. Recent concerns regarding potential cardiovascular toxicities associated with cox-2 selective inhibitors may favor non-selective NSAID/PPI co-therapy as the preferred choice. Concomitant use of low-dose aspirin with any NSAID increases the risk of gastrointestinal complications and diminishes the improved gastrointestinal safety profile of celecoxib; whereas use of ibuprofen plus PPI regimens may negate aspirin's antiplatelet benefits. Evidence shows that concurrent use of a non-selective NSAID (such as naproxen) plus a PPI is as effective in preventing NSAID gastropathy as celecoxib, and may be more cost-effective. Patients failing or intolerant to this therapy would be candidates for celecoxib at the lowest effective dose for the shortest duration of time. Potential benefits from using low-dose celecoxib with a PPI in patients previously experiencing bleeding ulcers while taking NSAIDs remains to be proven. An evidence-based debate is presented to assist clinicians with the difficult decision-making process of preventing NSAID gastropathy while minimizing other complications.
Mechanism of equalization of proton and neutron radii and the Coulomb anomaly

International Nuclear Information System (INIS)

Caurier, E.; Poves, A.; Zuker, A.

1980-01-01

It is shown that a one parameter modification of the effective forces allows to resolve the Coulomb energy anomalies in the Ca region within the framework of Hartree Fock (HF) and isospin projected Hartree Fock (IPHF) theories. A simple microscopic mechanism of equalization of neutron and proton radii is invoked to produce results consistent with available data
Circulating aldosterone induces the apical accumulation of the proton pumping V-ATPase and increases proton secretion in clear cells in the caput epididymis.

Science.gov (United States)

Roy, Jeremy W; Hill, Eric; Ruan, Ye Chun; Vedovelli, Luca; Păunescu, Teodor G; Brown, Dennis; Breton, Sylvie

2013-08-15

Clear cells express the vacuolar proton-pumping H(+)-ATPase (V-ATPase) and acidify the lumen of the epididymis, a process that is essential for male fertility. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance in the epididymis, and a previous study showed binding of aldosterone exclusively to epididymal clear cells (Hinton BT, Keefer DA. Steroid Biochem 23: 231-233, 1985). We examined here the role of aldosterone in the regulation of V-ATPase in the epididymis. RT-PCR showed expression of the mineralocorticoid receptor [MR; nuclear receptor subfamily 3, group C member 2 (NR3C2)] and 11-β-dehydrogenase isozyme 2 (HSD11β2) mRNAs specifically in clear cells, isolated by fluorescence-activated cell sorting from B1-enhanced green fluorescent protein (EGFP) mice. Tail vein injection of adult rats with aldosterone, 1,2-dioctanoyl-sn-glycerol (DOG), or 8-(4-chlorophenylthio)-cAMP (cpt-cAMP) induced V-ATPase apical membrane accumulation and extension of V-ATPase-labeled microvilli in clear cells in the caput epididymis but not in the cauda. V-ATPase activity was measured in EGFP-expressing clear cells using the intracellular pH (pHi)-sensing dye seminaphthorhodafluor-5F-5-(and 6)-carboxylic acid, acetoxymethyl ester acetate (SNARF-5F). Aldosterone induced a rapid increase in the rate of Na(+)- and bicarbonate-independent pHi recovery following an NH4Cl-induced acid load in clear cells isolated from the caput but not the cauda. This effect was abolished by concanamycin A, spironolactone, and chelerythrine but not myristoylated-protein kinase inhibitor (mPKI) or mifepristone. Thus aldosterone increases V-ATPase-dependent proton secretion in clear cells in the caput epididymis via MR/NR3C2 and PKC activation. This study, therefore, identifies aldosterone as an active member of the RAAS for the regulation of luminal acidification in the proximal epididymis.
Cognitive impact after short-term exposure to different proton pump inhibitors: assessment using CANTAB software.

Science.gov (United States)

Akter, Sanjida; Hassan, Md Rajib; Shahriar, Mohammad; Akter, Nahia; Abbas, Md Golam; Bhuiyan, Mohiuddin Ahmed

2015-12-27

Studies have shown that proton pump inhibitors (PPIs) increase the brain burden of amyloid-beta (Aβ) and also create vitamin B12 deficiency. However, these two phenomena have deleterious effect on cognition and Alzheimer's disease (AD). Since the use of PPIs has increased tremendously for the last few years, it is of great public health importance to investigate the cognitive impact of PPIs. Hence, the purpose of this study was to investigate the degree of neuropsychological association of each PPI with different cognitive functions. Sixty volunteers of either gender were recruited and divided randomly into six groups: five test groups for five classes of PPIs and one control group. All the groups participated in the five computerized neuropsychological tests (nine subtests) of the Cambridge Neuropsychological Test Automated Battery twice: at the beginning of the study and 7 days thereafter. We found statistically and clinically significant impairment in visual memory, attention, executive function, and working and planning function. One-way analysis of variance findings showed that all PPIs had a similar negative impact on cognition. However, paired-samples t tests indicated that omeprazole showed significant (p benefits of prescribing these medications. A study done for a longer period of time with a larger sample size might yield better results.
Proton Pump Inhibitor Use Is Associated With a Reduced Risk of Infection with Intestinal Protozoa.

Science.gov (United States)

Sheele, Johnathan M

2017-12-01

Proton pump inhibitors (PPIs) can kill some human protozoan parasites in cell culture better than the drug metronidazole. Clinical data showing an antiprotozoal effect for PPIs are lacking. The objective of the study is to determine if PPI use is associated with a reduced risk of having intestinal parasites. We obtained electronic medical record data for all persons who received a stool ova and parasite (O & P) examination at our tertiary care academic medical center in Cleveland, Ohio, between January 2000 and September 2014. We obtained the person's age, whether they were taking a PPI at the time of the O & P examination, and whether the pathology report indicated the presence of any parasites. χ 2 with Yates correction was used to determine if PPI use was associated with stool protozoa. Three intestinal protozoa were identified in 1199 patients taking a PPI (0.3%), and 551 intestinal parasites were identified in the 14,287 patients not taking a PPI (3.9%). There was a statistically significant lower likelihood of finding protozoa in the stool of a person taking a PPI compared with those not taking a PPI (P protozoa reported on stool O & P examination compared with those not taking a PPI. Copyright © 2017 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.
Influence of proton pump inhibitors on gastritis diagnosis and pathologic gastric changes.

Science.gov (United States)

Nasser, Soumana C; Slim, Mahmoud; Nassif, Jeanette G; Nasser, Selim M

2015-04-21

To investigate the influence of proton pump inhibitors (PPIs) exposure on the diagnosis of Helicobacter pylori (H. pylori) gastritis and intestinal metaplasia. Chronic PPI use is associated with masking of H. pylori infection. Patients with H. pylori infection are predisposed to gastric and duodenal ulcers, and long-term infection with this organism has been associated with gastric mucosal atrophy and serious long-term complications, such as gastric lymphoma and adenocarcinoma. Three hundred patients diagnosed with gastritis between January 2008 and April 2010 were included in our study. The computerized medical database of these patients was reviewed retrospectively in order to assess whether the type of gastritis diagnosed (H. pylori vs non-H. pylori gastritis) is influenced by PPI exposure. H. pylori density was graded as low, if corresponding to mild density following the Updated Sydney System, or high, if corresponding to moderate or severe densities in the Updated Sydney System. Patients were equally distributed between males and females with a median age at the time of diagnosis of 50 years old (range: 20-87). The histological types of gastritis were classified as H. pylori gastritis (n = 156, 52%) and non-H. pylori gastritis (n = 144, 48%). All patients with non-H. pylori gastritis had inactive chronic gastritis. Patients with no previous PPI exposure were more likely to be diagnosed with H. pylori gastritis than those with previous PPI exposure (71% vs 34.2%, P gastritis and leads to a significant drop in H. pylori densities and to an increased risk of intestinal metaplasia. The use of PPIs masks H. pylori infection, promotes the diagnosis of non-H. pylori inactive chronic gastritis diagnosis, and increases the incidence of intestinal metaplasia.
Quarkonium production in high energy proton-proton and proton-nucleus collisions

International Nuclear Information System (INIS)

Conesa del Valle, Z.; Corcella, G.; Fleuret, F.; Ferreiro, E.G.; Kartvelishvili, V.; Kopeliovich, B.; Lansberg, J.P.; Lourenco, C.; Martinez, G.; Papadimitriou, V.; Satz, H.; Scomparin, E.; Ullrich, T.; Teryaev, O.; Vogt, R.; Wang, J.X.

2011-01-01

We present a brief overview of the most relevant current issues related to quarkonium production in high energy proton-proton and proton-nucleus collisions along with some perspectives. After reviewing recent experimental and theoretical results on quarkonium production in pp and pA collisions, we discuss the emerging field of polarisation studies. Afterwards, we report on issues related to heavy-quark production, both in pp and pA collisions, complemented by AA collisions. To put the work in broader perpectives, we emphasize the need for new observables to investigate the quarkonium production mechanisms and reiterate the qualities that make quarkonia a unique tool for many investigations in particle and nuclear physics.
H+-type and OH- -type biological protonic semiconductors and complementary devices.

Science.gov (United States)

Deng, Yingxin; Josberger, Erik; Jin, Jungho; Roudsari, Anita Fadavi; Rousdari, Anita Fadavi; Helms, Brett A; Zhong, Chao; Anantram, M P; Rolandi, Marco

2013-10-03

Proton conduction is essential in biological systems. Oxidative phosphorylation in mitochondria, proton pumping in bacteriorhodopsin, and uncoupling membrane potentials by the antibiotic Gramicidin are examples. In these systems, H(+) hop along chains of hydrogen bonds between water molecules and hydrophilic residues - proton wires. These wires also support the transport of OH(-) as proton holes. Discriminating between H(+) and OH(-) transport has been elusive. Here, H(+) and OH(-) transport is achieved in polysaccharide- based proton wires and devices. A H(+)- OH(-) junction with rectifying behaviour and H(+)-type and OH(-)-type complementary field effect transistors are demonstrated. We describe these devices with a model that relates H(+) and OH(-) to electron and hole transport in semiconductors. In turn, the model developed for these devices may provide additional insights into proton conduction in biological systems.
Detection of pump degradation

International Nuclear Information System (INIS)

Greene, R.H.; Casada, D.A.; Ayers, C.W.

1995-08-01

This Phase II Nuclear Plant Aging Research study examines the methods of detecting pump degradation that are currently employed in domestic and overseas nuclear facilities. This report evaluates the criteria mandated by required pump testing at U.S. nuclear power plants and compares them to those features characteristic of state-of-the-art diagnostic programs and practices currently implemented by other major industries. Since the working condition of the pump driver is crucial to pump operability, a brief review of new applications of motor diagnostics is provided that highlights recent developments in this technology. The routine collection and analysis of spectral data is superior to all other technologies in its ability to accurately detect numerous types and causes of pump degradation. Existing ASME Code testing criteria do not require the evaluation of pump vibration spectra but instead overall vibration amplitude. The mechanical information discernible from vibration amplitude analysis is limited, and several cases of pump failure were not detected in their early stages by vibration monitoring. Since spectral analysis can provide a wealth of pertinent information concerning the mechanical condition of rotating machinery, its incorporation into ASME testing criteria could merit a relaxation in the monthly-to-quarterly testing schedules that seek to verify and assure pump operability. Pump drivers are not included in the current battery of testing. Operational problems thought to be caused by pump degradation were found to be the result of motor degradation. Recent advances in nonintrusive monitoring techniques have made motor diagnostics a viable technology for assessing motor operability. Motor current/power analysis can detect rotor bar degradation and ascertain ranges of hydraulically unstable operation for a particular pump and motor set. The concept of using motor current or power fluctuations as an indicator of pump hydraulic load stability is presented

Detection of pump degradation

Energy Technology Data Exchange (ETDEWEB)

Greene, R.H.; Casada, D.A.; Ayers, C.W. [and others

1995-08-01

This Phase II Nuclear Plant Aging Research study examines the methods of detecting pump degradation that are currently employed in domestic and overseas nuclear facilities. This report evaluates the criteria mandated by required pump testing at U.S. nuclear power plants and compares them to those features characteristic of state-of-the-art diagnostic programs and practices currently implemented by other major industries. Since the working condition of the pump driver is crucial to pump operability, a brief review of new applications of motor diagnostics is provided that highlights recent developments in this technology. The routine collection and analysis of spectral data is superior to all other technologies in its ability to accurately detect numerous types and causes of pump degradation. Existing ASME Code testing criteria do not require the evaluation of pump vibration spectra but instead overall vibration amplitude. The mechanical information discernible from vibration amplitude analysis is limited, and several cases of pump failure were not detected in their early stages by vibration monitoring. Since spectral analysis can provide a wealth of pertinent information concerning the mechanical condition of rotating machinery, its incorporation into ASME testing criteria could merit a relaxation in the monthly-to-quarterly testing schedules that seek to verify and assure pump operability. Pump drivers are not included in the current battery of testing. Operational problems thought to be caused by pump degradation were found to be the result of motor degradation. Recent advances in nonintrusive monitoring techniques have made motor diagnostics a viable technology for assessing motor operability. Motor current/power analysis can detect rotor bar degradation and ascertain ranges of hydraulically unstable operation for a particular pump and motor set. The concept of using motor current or power fluctuations as an indicator of pump hydraulic load stability is presented.
A QUANTUM MECHANICAL STUDY OF THE PROTONATION AND COVALENT HYDRATION OF QUINAZOLINE IN THE PRESENCE OF METAL CATIONS

Science.gov (United States)

We have investigated the protonation and reversible covalent hydration of quinazoline in the presence of Li+, Na+, and Ca2+ ions using ab initio quantum mechanical calculations at the MP2/6-31G**//HF/6-31G*level of theory. Proton affinities, enthalpies of hydration at 298.15K (DH...
Mechanical design of beam extractor system for cyclotron proton 13 MeV

International Nuclear Information System (INIS)

Ihwanul Aziz; Widdi Usada

2012-01-01

Mechanical design of beam extractor system for 13 MeV proton cyclotron has been carried out. In cyclotron there are two extractor systems, the first is electrostatic deflector system, and the second is stripper system. This stripper serves to change negative charged of hydrogen ions to become positive charged hydrogen ions (protons). In proton cyclotron, the carbon foil is used as a stripper. Mechanical extractor system consists of a carbon foil holder and a driver system to control the position of foil holder and to change the foil. The driver system consists of a stepper motor extractor, a feed-through, a gear, a shaft, and a buffer. After some calculation the obtained component data as the foil follow holder is made of aluminum has total length of 12.25 mm, total width of 10 mm and the total thickness of 2.5 mm, while the length of each extractor arm is made of aluminum 90 mm, width is 30 mm, its height is 10 mm , the total volume is 7,392 x 10-5 and a mass of 0.1995 kg. Extractor drive system includes a stepper motor having a maximum of 4 lb-ft of torque, feed through, gear, shaft, and a buffer. Required torque is 0.16 Nm or 0.12 lb-ft diameter shaft to support the extractor arm is 29 mm. Bolt fastener for the buffer is a type of metric M6 bolt, so that the used seals viton O-ring with seal diameter of 6 mm and DN 40 CF flange. (author)
Tunneling induced electron transfer between separated protons

Science.gov (United States)

Vindel-Zandbergen, Patricia; Meier, Christoph; Sola, Ignacio R.

2018-04-01

We study electron transfer between two separated protons using local control theory. In this symmetric system one can favour a slow transfer by biasing the algorithm, achieving high efficiencies for fixed nuclei. The solution can be parametrized using a sequence of a pump followed by a dump pulse that lead to tunneling-induced electron transfer. Finally, we study the effect of the nuclear kinetic energy on the efficiency. Even in the absence of relative motion between the protons, the spreading of the nuclear wave function is enough to reduce the yield of electronic transfer to less than one half.
Ring current proton decay by charge exchange

Science.gov (United States)

Smith, P. H.; Hoffman, R. A.; Fritz, T.

1975-01-01

Explorer 45 measurements during the recovery phase of a moderate magnetic storm have confirmed that the charge exchange decay mechanism can account for the decay of the storm-time proton ring current. Data from the moderate magnetic storm of 24 February 1972 was selected for study since a symmetrical ring current had developed and effects due to asymmetric ring current losses could be eliminated. It was found that after the initial rapid decay of the proton flux, the equatorially mirroring protons in the energy range 5 to 30 keV decayed throughout the L-value range of 3.5 to 5.0 at the charge exchange decay rate calculated by Liemohn. After several days of decay, the proton fluxes reached a lower limit where an apparent equilibrium was maintained, between weak particle source mechanisms and the loss mechanisms, until fresh protons were injected into the ring current region during substorms. While other proton loss mechanisms may also be operating, the results indicate that charge exchange can entirely account for the storm-time proton ring current decay, and that this mechanism must be considered in all studies involving the loss of proton ring current particles.
Mechanical damage due to corrosion of parts of pump technology and valves of LWR power installations

International Nuclear Information System (INIS)

Hron, J.; Krumpl, M.

1986-01-01

Two types are described of uneven corrosion of austenitic chromium-nickel steel: pitting and slit corrosion. The occurrence of slit corrosion is typical of parts of pumping technology and valves. The corrosion damage of austenitic chromium-nickel steels spreads as intergranular, transgranular or mixed corrosion. In nuclear power facilities with LWR's, intergranular corrosion is due to chlorides and sulphur compounds while transgranular corrosion is due to the presence of dissolved oxygen and chlorides. In mechanically stressed parts, stress corrosion takes place. The recommended procedures are discussed of reducing the corrosion-mechanical damage of pumping equipment of light water reactors during design, production and assembly. During the service of the equipment, corrosion cracks are detected using nondestructive methods and surface cracks are repaired by grinding and welding. (E.S.)
The proton radius puzzle

Science.gov (United States)

Bonesini, Maurizio

2017-12-01

The FAMU (Fisica degli Atomi Muonici) experiment has the goal to measure precisely the proton Zemach radius, thus contributing to the solution of the so-called proton radius "puzzle". To this aim, it makes use of a high-intensity pulsed muon beam at RIKEN-RAL impinging on a cryogenic hydrogen target with an high-Z gas admixture and a tunable mid-IR high power laser, to measure the hyperfine (HFS) splitting of the 1S state of the muonic hydrogen. From the value of the exciting laser frequency, the energy of the HFS transition may be derived with high precision ( 10-5) and thus, via QED calculations, the Zemach radius of the proton. The experimental apparatus includes a precise fiber-SiPMT beam hodoscope and a crown of eight LaBr3 crystals and a few HPGe detectors for detection of the emitted characteristic X-rays. Preliminary runs to optimize the gas target filling and its operating conditions have been taken in 2014 and 2015-2016. The final run, with the pump laser to drive the HFS transition, is expected in 2018.
Local mechanical stress relaxation of Gunn diodes irradiated by protons

International Nuclear Information System (INIS)

Gradoboev, A V; Tesleva, E P

2017-01-01

The aim of the work is studying the impact of Gunn diodes thermocompression bonding conditions upon their resistance to being radiated with protons of various energies. It was established that the tough conditions of Gunn diodes thermocompression bonding results in local mechanic stresses introduced into the active layer of the device, reduction of electron mobility because of the faults introduction and, subsequently, to reduction of operating current, power of UHF generation, percentage of qualitative units production and general reduction of production efficiency of the devices with required characteristics. Irradiation of Gunn diodes produced under the tough conditions of thermocompression bonding with protons which energy is (40–60) MeV with an absorbed dose of (1–6)·10 2 Gy does not practically reduce the radiation resistance of Gunn diodes produced with application of the given technique. This technique can be recommended for all semiconductor devices on the base of GaAs, which parameters depend significantly upon the mobility of the electrons, to increase the efficiency of production. (paper)
Pumps in wearable ultrafiltration devices: pumps in wuf devices.

Science.gov (United States)

Armignacco, Paolo; Garzotto, Francesco; Bellini, Corrado; Neri, Mauro; Lorenzin, Anna; Sartori, Marco; Ronco, Claudio

2015-01-01

The wearable artificial kidney (WAK) is a device that is supposed to operate like a real kidney, which permits prolonged, frequent, and continuous dialysis treatments for patients with end-stage renal disease (ESRD). Its functioning is mainly related to its pumping system, as well as to its dialysate-generating and alarm/shutoff ones. A pump is defined as a device that moves fluids by mechanical action. In such a context, blood pumps pull blood from the access side of the dialysis catheter and return the blood at the same rate of flow. The main aim of this paper is to review the current literature on blood pumps, describing the way they have been functioning thus far and how they are being engineered, giving details about the most important parameters that define their quality, thus allowing the production of a radar comparative graph, and listing ideal pumps' features. © 2015 S. Karger AG, Basel.
Effect of proton pump inhibitors on the serum concentrations of the selective serotonin reuptake inhibitors citalopram, escitalopram, and sertraline.

Science.gov (United States)

Gjestad, Caroline; Westin, Andreas A; Skogvoll, Eirik; Spigset, Olav

2015-02-01

The selective serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram, and sertraline are all metabolized by the cytochrome P-450 isoenzyme CYP2C19, which is inhibited by the proton pump inhibitors (PPIs) omeprazole, esomeprazole, lansoprazole, and pantoprazole. The aim of the present study was to evaluate the effect of these PPIs on the serum concentrations of citalopram, escitalopram, and sertraline. Serum concentrations from patients treated with citalopram, escitalopram, or sertraline were obtained from a routine therapeutic drug monitoring database, and samples from subjects concomitantly using PPIs were identified. Dose-adjusted SSRI serum concentrations were calculated to compare data from those treated and those not treated with PPIs. Citalopram concentrations were significantly higher in patients treated with omeprazole (+35.3%; P Escitalopram concentrations were significantly higher in patients treated with omeprazole (+93.9%; P escitalopram is affected to a greater extent than are citalopram and sertraline. When omeprazole or esomeprazole are used in combination with escitalopram, a 50% dose reduction of the latter should be considered.
High-doses of proton pump inhibitors in refractory gastro-intestinal cancer: A case series and the state of art.

Science.gov (United States)

Falcone, Rosa; Roberto, Michela; D'Antonio, Chiara; Romiti, Adriana; Milano, Annalisa; Onesti, Concetta Elisa; Marchetti, Paolo; Fais, Stefano

2016-12-01

In recent years, proton pump inhibitors (PPIs) have been investigated at high-dose to modulate tumour microenvironment acidification thus restoring chemotherapeutic sensitivity. Moreover, several clinical data supports the role of cytotoxic drugs at low-dose continuously delivered as anticancer therapy. Clinical records of three patients affected with gastrointestinal cancer refractory to standard treatments, who had received a combination of high-dose rabeprazole and metronomic chemotherapy were reviewed. The first case, a 78-year-old man was treated for lung metastasis from colon adenocarcinoma. The second case, a 73-year-old man was treated for metastatic rectal cancer to the liver. The third one, a 68-year-old man, underwent the combination regimen for colon cancer with lung, liver and peritoneal metastases. Despite the failure of previous standard chemotherapy for metastatic disease, good clinical outcome was shown in these patients treated with an unconventional association of high-dose PPIs and metronomic chemotherapy. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
EFFECTS OF PROTON PUMP INHIBITORS ON DENTAL EROSIONS CAUSED BY GASTROESOPHAGEAL REFLUX DISEASE

Directory of Open Access Journals (Sweden)

Andrei Vasile OLTEANU

2015-12-01

Full Text Available Background: Numerous studies worldwide have assessed the association between dental erosions or other related oral manifestations, and the gastroesophageal reflux disease (GERD. Nowadays, one of the main therapeutic resources of GERD is represented by proton pump inhibitors (PPIs. Adequate salivary secretions and flow are considered mandatory for the protection of both teeth and esophageal mucosa. The aim of the present study was to evaluate the possible correlation between GERD treatment options and subsequent control of oral manifestation, taking as premises that either PPIs or dietary and lifestyle changes may control oral patterns of GERD by acting on salivary secretions. Methods: 48 clinically diagnosed GERD adult patients with oral manifestations, mainly erosions, were included in the study, none of which showing alarming symptoms that would require further gastroenterologic examination. Oral examination evaluated the DMF (decayed, missing, filled and OHI-S (Simplified Oral Hygiene indices. Salivary flow was evaluated by the Saxon test. 25 patients were prescribed dietary and lifestyle measures and PPIs (omeprazole – 20 mg, whereas 23 patients were managed only through dietary and lifestyle modifications. General assessment was performed at the time of diagnosis and 4 weeks afterwards. Results: No significant differences as to the DMF index, OHI-S index or Saxon test were found over the 4 weeks management between the groups. Conclusions: Oral manifestation of GERD may be caused by impaired salivary secretions and flow, otherwise no - positive or negative - effect could be secondary to PPI therapy. Accordingly, complex oral rehabilitation of GERD patients and collaboration between gastroenterologists and dentists should be promoted.
Association of Proton Pump Inhibitors Usage with Risk of Pneumonia in Dementia Patients.

Science.gov (United States)

Ho, Sai-Wai; Teng, Ying-Hock; Yang, Shun-Fa; Yeh, Han-Wei; Wang, Yu-Hsun; Chou, Ming-Chih; Yeh, Chao-Bin

2017-07-01

To determine the association between usages of proton pump inhibitors (PPIs) and subsequent risk of pneumonia in dementia patients. Retrospective cohort study. Taiwanese National Health Insurance Research Database. The study cohort consisted of 786 dementia patients with new PPI usage and 786 matched dementia patients without PPI usage. The study endpoint was defined as the occurrence of pneumonia. The Cox proportional hazard model was used to estimate the pneumonia risk. Defined daily dose methodology was applied to evaluate the cumulative and dose-response relationships of PPI. Incidence of pneumonia was higher among patients with PPI usage (adjusted hazard ratio (HR) = 1.89; 95% CI = 1.51-2.37). Cox model analysis also demonstrated that age (adjusted HR = 1.05; 95% CI = 1.03-1.06), male gender (adjusted HR = 1.57; 95% CI = 1.25-1.98), underlying cerebrovascular disease (adjusted HR = 1.30; 95% CI = 1.04-1.62), chronic pulmonary disease (adjusted HR = 1.39; 95% CI = 1.09-1.76), congestive heart failure (adjusted HR = 1.54; 95% CI = 1.11-2.13), diabetes mellitus (adjusted HR = 1.54; 95% CI = 1.22-1.95), and usage of antipsychotics (adjusted HR = 1.29; 95% CI = 1.03-1.61) were independent risk factors for pneumonia. However, usage of cholinesterase inhibitors and histamine receptor-2 antagonists were shown to decrease pneumonia risk. PPI usage in dementia patients is associated with an 89% increased risk of pneumonia. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.
Direct solar-pumped iodine laser amplifier

Science.gov (United States)

Han, Kwang S.

1987-01-01

This semiannual progress report covers the period from March 1, 1987 to September 30, 1987 under NASA grant NAG1-441 entitled 'Direct solar-pumped iodine laser amplifier'. During this period Nd:YAG and Nd:Cr:GSGG crystals have been tested for the solar-simulator pumped cw laser, and loss mechanisms of the laser output power in a flashlamp-pumped iodine laser also have been identified theoretically. It was observed that the threshold pump-beam intensities for both Nd:YAG and Nd:Cr:GSGG crystals were about 1000 solar constants, and the cw laser operation of the Nd:Cr:GSGG crystal was more difficult than that of the Nd:YAG crystal under the solar-simulator pumping. The possibility of the Nd:Cr:GSGG laser operation with a fast continuously chopped pumping was also observed. In addition, good agreement between the theoretical calculations and the experimental data on the loss mechanisms of a flashlamp-pumped iodine laser at various fill pressures and various lasants was achieved.
Increased proximal reflux in a hypersensitive esophagus might explain symptoms resistant to proton pump inhibitors in patients with gastroesophageal reflux disease.

Science.gov (United States)

Rohof, Wout O; Bennink, Roelof J; de Jonge, Hugo; Boeckxstaens, Guy E

2014-10-01

Approximately 30% of patients with gastroesophageal reflux disease have symptoms resistant to treatment with proton pump inhibitors (PPIs). Several mechanisms such as esophageal hypersensitivity, increased mucosal permeability, and possibly the position of the gastric acid pocket might underlie a partial response to PPIs. To what extent these mechanisms interact and contribute to PPI-resistant symptoms, however, has not been investigated previously. In 18 gastroesophageal reflux disease patients (9 PPI responders and 9 PPI partial responders), esophageal sensitivity, mucosal permeability, and postprandial reflux parameters were determined during PPI use. Esophageal sensitivity for distension was measured by gradual balloon inflation at 5 and 15 cm above the lower esophageal sphincter. The mucosal permeability of 4 esophageal biopsy specimens per patient was determined in Ussing chambers by measuring the transepithelial electrical resistance and transmucosal flux of fluorescein. Postprandial reflux parameters were determined using concurrent high-resolution manometry/pH impedance after a standardized meal. In addition, the acid pocket was visualized using scintigraphy. No difference in the rate of postprandial acid reflux, in the pH of the acid pocket (PPI responders 3.7 ± 0.7 vs PPI partial responders 4.2 ± 0.4; P = .54), or in the position of the acid pocket was observed in PPI partial responders compared with PPI responders. In addition, the permeability of the esophageal mucosa was similar in both groups, as shown by a similar transepithelial electrical resistance and flux of fluorescein. PPI partial responders had more reflux episodes with a higher mean proximal extent, compared with PPI responders, and were more sensitive to balloon distension, both in the upper and lower esophagus. PPI-resistant symptoms most likely are explained by increased proximal reflux in a hypersensitive esophagus and less likely by increased mucosal permeability or the position of
Scroll vacuum pump

Energy Technology Data Exchange (ETDEWEB)

Morishita, Etsuo; Suganami, Takuya; Nishida, Mitsuhiro; Kitora, Yoshihisa; Yamamoto, Sakuei; Fujii, Kosaburo

1988-02-25

An effort is made to apply a scroll machine to development of a vacuum pump. In view of mechanical simplification and load patterns, the vacuum pump uses a rotating mechanism to produce paired vortices rotating around each center. Chip seal and atmospheric pressure are utilized for axial gap sealing while a spring and atmospheric pressure for the radial gap sealing. In both gaps, the sealing direction is stationary relative to the environment during rotation, making it much easier to achieve effective sealing as compared to oscillating pumps. Since the compression ratio is high in vacuum pumps, a zero top clearance form is adopted for the central portion of vortices and an gas release valve is installed in the rotating axis. A compact Oldham coupling with a small inertia force is installed behind the vortices to maintain the required phase relations between the vortices. These improvements result in a vacuum of 1 Pa for dry operation and 10/sup -2/ Pa for oil flooded operation of a single-stage scroll machine at 1800 rpm. (5 figs, 1 tab, 4 refs)
Role of Asp544 in subunit I for Na+ pumping by Vitreoscilla cytochrome bo

International Nuclear Information System (INIS)

Chung, Yeon T.; Stark, Benjamin C.; Webster, Dale A.

2006-01-01

The conserved Glu540 in subunit I of Escherichia coli cytochrome bo (a H + pump) is replaced by Asp544 in the Vitreoscilla enzyme (a Na + pump). Site-directed mutagenesis of the Vitreoscilla cytochrome bo operon changed this Asp to Glu, and both wild type and mutant cyo's were transformed into E. coli strain GV100, which lacks cytochrome bo. Compared to the wild type transformant the Asp544Glu transformant had decreased ability to pump Na + as well as decreased stimulation in respiratory activity in the presence of Na + . Preliminary experiments indicated that this mutant also had increased ability to pump protons, suggesting that this single change may provide cation pumping specificity in this group of enzymes
H+-type and OH−-type biological protonic semiconductors and complementary devices

Science.gov (United States)

Deng, Yingxin; Josberger, Erik; Jin, Jungho; Rousdari, Anita Fadavi; Helms, Brett A.; Zhong, Chao; Anantram, M. P.; Rolandi, Marco

2013-01-01

Proton conduction is essential in biological systems. Oxidative phosphorylation in mitochondria, proton pumping in bacteriorhodopsin, and uncoupling membrane potentials by the antibiotic Gramicidin are examples. In these systems, H+ hop along chains of hydrogen bonds between water molecules and hydrophilic residues – proton wires. These wires also support the transport of OH− as proton holes. Discriminating between H+ and OH− transport has been elusive. Here, H+ and OH− transport is achieved in polysaccharide- based proton wires and devices. A H+- OH− junction with rectifying behaviour and H+-type and OH−-type complementary field effect transistors are demonstrated. We describe these devices with a model that relates H+ and OH− to electron and hole transport in semiconductors. In turn, the model developed for these devices may provide additional insights into proton conduction in biological systems. PMID:24089083
Negative Effect of Proton-pump Inhibitors (PPIs) on Helicobacter pylori Growth, Morphology, and Urease Test and Recovery after PPI Removal--An In vitro Study.

Science.gov (United States)

Saniee, Parastoo; Shahreza, Somayeh; Siavoshi, Farideh

2016-04-01

Proton-pump inhibitor (PPI) consumption does lead to false-negative results of Helicobacter pylori diagnostic tests such as biopsy culture and rapid urease test (RUT). Helicobacter pylori isolates from 112 dyspeptic patients with (56.5%) or without (43.5%) PPI consumption were recruited for examining the negative effects of omeprazole (OMP), lansoprazole (LPZ), and pantoprazole (PAN) on H. pylori viability, morphology, and urease, in vitro. The effect of a sublethal concentration of OMP on bacterial features and their recovery after removal of OMP was also assessed. Of 112 culture-positive gastric biopsies, 87.5% were RUT positive and 12.5% RUT negative. There was a significant correlation between negative RUT results and PPI consumption (p urease of 90.3% of isolates between 0 and 40 minutes and 54.4% between 20 and 40 minutes, respectively. PAN did not inhibit H. pylori growth and urease. Three 3-day (9 days) consecutive subcultures of H. pylori on brucella blood agar (BBA) supplemented with OMP resulted in reduced bacterial viability (1+), compared with control (4+), change of spiral morphology to coccoid, and reduction in pink color intensity in urea agar. Bacterial growth (1+), morphology, and urease test did not improve after the first 3-day and second 3-day (6 days) subcultures on BBA. However, relative recovery occurred after the third 3-day (9 days) subculture and complete recovery was observed after the fourth 3-day (12 days) subculture, as confluent growth (4+), 100% spiral cells, and strong urease test. Proton-pump Inhibitors exert transient negative effects on H. pylori viability, morphology, and urease test. Accordingly, cessation of PPI consumption at least 12 days before endoscopy could help avoiding false-negative results of H. pylori diagnostic tests. © 2015 John Wiley & Sons Ltd.
Search for evidence of the type-III seesaw mechanism in multilepton final states in proton-proton collisions at $ \\sqrt{s} = $ 13 TeV

CERN Document Server

Sirunyan, Albert M; CMS Collaboration; Adam, Wolfgang; Ambrogi, Federico; Asilar, Ece; Bergauer, Thomas; Brandstetter, Johannes; Brondolin, Erica; Dragicevic, Marko; Erö, Janos; Flechl, Martin; Friedl, Markus; Fruehwirth, Rudolf; Ghete, Vasile Mihai; Grossmann, Johannes; Hrubec, Josef; Jeitler, Manfred; König, Axel; Krammer, Natascha; Krätschmer, Ilse; Liko, Dietrich; Madlener, Thomas; Mikulec, Ivan; Pree, Elias; Rabady, Dinyar; Rad, Navid; Rohringer, Herbert; Schieck, Jochen; Schöfbeck, Robert; Spanring, Markus; Spitzbart, Daniel; Waltenberger, Wolfgang; Wittmann, Johannes; Wulz, Claudia-Elisabeth; Zarucki, Mateusz; Chekhovsky, Vladimir; Mossolov, Vladimir; Suarez Gonzalez, Juan; De Wolf, Eddi A; Di Croce, Davide; Janssen, Xavier; Lauwers, Jasper; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Remortel, Nick; Abu Zeid, Shimaa; Blekman, Freya; D'Hondt, Jorgen; De Bruyn, Isabelle; De Clercq, Jarne; Deroover, Kevin; Flouris, Giannis; Lontkovskyi, Denys; Lowette, Steven; Moortgat, Seth; Moreels, Lieselotte; Python, Quentin; Skovpen, Kirill; Tavernier, Stefaan; Van Doninck, Walter; Van Mulders, Petra; Van Parijs, Isis; Brun, Hugues; Clerbaux, Barbara; De Lentdecker, Gilles; Delannoy, Hugo; Fasanella, Giuseppe; Favart, Laurent; Goldouzian, Reza; Grebenyuk, Anastasia; Karapostoli, Georgia; Lenzi, Thomas; Luetic, Jelena; Maerschalk, Thierry; Marinov, Andrey; Randle-conde, Aidan; Seva, Tomislav; Vander Velde, Catherine; Vanlaer, Pascal; Vannerom, David; Yonamine, Ryo; Zenoni, Florian; Zhang, Fengwangdong; Cimmino, Anna; Cornelis, Tom; Dobur, Didar; Fagot, Alexis; Gul, Muhammad; Khvastunov, Illia; Poyraz, Deniz; Roskas, Christos; Salva Diblen, Sinem; Tytgat, Michael; Verbeke, Willem; Zaganidis, Nicolas; Bakhshiansohi, Hamed; Bondu, Olivier; Brochet, Sébastien; Bruno, Giacomo; Caudron, Adrien; De Visscher, Simon; Delaere, Christophe; Delcourt, Martin; Francois, Brieuc; Giammanco, Andrea; Jafari, Abideh; Komm, Matthias; Krintiras, Georgios; Lemaitre, Vincent; Magitteri, Alessio; Mertens, Alexandre; Musich, Marco; Piotrzkowski, Krzysztof; Quertenmont, Loic; Vidal Marono, Miguel; Wertz, Sébastien; Beliy, Nikita; Aldá Júnior, Walter Luiz; Alves, Fábio Lúcio; Alves, Gilvan; Brito, Lucas; Correa Martins Junior, Marcos; Hensel, Carsten; Moraes, Arthur; Pol, Maria Elena; Rebello Teles, Patricia; Belchior Batista Das Chagas, Ewerton; Carvalho, Wagner; Chinellato, Jose; Custódio, Analu; Melo Da Costa, Eliza; Da Silveira, Gustavo Gil; De Jesus Damiao, Dilson; Fonseca De Souza, Sandro; Huertas Guativa, Lina Milena; Malbouisson, Helena; Melo De Almeida, Miqueias; Mora Herrera, Clemencia; Mundim, Luiz; Nogima, Helio; Santoro, Alberto; Sznajder, Andre; Tonelli Manganote, Edmilson José; Torres Da Silva De Araujo, Felipe; Vilela Pereira, Antonio; Ahuja, Sudha; Bernardes, Cesar Augusto; Tomei, Thiago; De Moraes Gregores, Eduardo; Mercadante, Pedro G; Novaes, Sergio F; Padula, Sandra; Romero Abad, David; Ruiz Vargas, José Cupertino; Aleksandrov, Aleksandar; Hadjiiska, Roumyana; Iaydjiev, Plamen; Misheva, Milena; Rodozov, Mircho; Shopova, Mariana; Stoykova, Stefka; Sultanov, Georgi; Dimitrov, Anton; Glushkov, Ivan; Litov, Leander; Pavlov, Borislav; Petkov, Peicho; Fang, Wenxing; Gao, Xuyang; Ahmad, Muhammad; Bian, Jian-Guo; Chen, Guo-Ming; Chen, He-Sheng; Chen, Mingshui; Chen, Ye; Jiang, Chun-Hua; Leggat, Duncan; Liao, Hongbo; Liu, Zhenan; Romeo, Francesco; Shaheen, Sarmad Masood; Spiezia, Aniello; Tao, Junquan; Wang, Chunjie; Wang, Zheng; Yazgan, Efe; Zhang, Huaqiao; Zhao, Jingzhou; Ban, Yong; Chen, Geng; Li, Qiang; Liu, Shuai; Mao, Yajun; Qian, Si-Jin; Wang, Dayong; Xu, Zijun; Avila, Carlos; Cabrera, Andrés; Chaparro Sierra, Luisa Fernanda; Florez, Carlos; González Hernández, Carlos Felipe; Ruiz Alvarez, José David; Courbon, Benoit; Godinovic, Nikola; Lelas, Damir; Puljak, Ivica; Ribeiro Cipriano, Pedro M; Sculac, Toni; Antunovic, Zeljko; Kovac, Marko; Brigljevic, Vuko; Ferencek, Dinko; Kadija, Kreso; Mesic, Benjamin; Starodumov, Andrei; Susa, Tatjana; Ather, Mohsan Waseem; Attikis, Alexandros; Mavromanolakis, Georgios; Mousa, Jehad; Nicolaou, Charalambos; Ptochos, Fotios; Razis, Panos A; Rykaczewski, Hans; Finger, Miroslav; Finger Jr, Michael; Carrera Jarrin, Edgar; El-khateeb, Esraa; Elgammal, Sherif; Ellithi Kamel, Ali; Dewanjee, Ram Krishna; Kadastik, Mario; Perrini, Lucia; Raidal, Martti; Tiko, Andres; Veelken, Christian; Eerola, Paula; Pekkanen, Juska; Voutilainen, Mikko; Härkönen, Jaakko; Jarvinen, Terhi; Karimäki, Veikko; Kinnunen, Ritva; Lampén, Tapio; Lassila-Perini, Kati; Lehti, Sami; Lindén, Tomas; Luukka, Panja-Riina; Tuominen, Eija; Tuominiemi, Jorma; Tuovinen, Esa; Talvitie, Joonas; Tuuva, Tuure; Besancon, Marc; Couderc, Fabrice; Dejardin, Marc; Denegri, Daniel; Faure, Jean-Louis; Ferri, Federico; Ganjour, Serguei; Ghosh, Saranya; Givernaud, Alain; Gras, Philippe; Hamel de Monchenault, Gautier; Jarry, Patrick; Kucher, Inna; Locci, Elizabeth; Machet, Martina; Malcles, Julie; Negro, Giulia; Rander, John; Rosowsky, André; Sahin, Mehmet Özgür; Titov, Maksym; Abdulsalam, Abdulla; Antropov, Iurii; Baffioni, Stephanie; Beaudette, Florian; Busson, Philippe; Cadamuro, Luca; Charlot, Claude; Granier de Cassagnac, Raphael; Jo, Mihee; Lisniak, Stanislav; Lobanov, Artur; Martin Blanco, Javier; Nguyen, Matthew; Ochando, Christophe; Ortona, Giacomo; Paganini, Pascal; Pigard, Philipp; Regnard, Simon; Salerno, Roberto; Sauvan, Jean-Baptiste; Sirois, Yves; Stahl Leiton, Andre Govinda; Strebler, Thomas; Yilmaz, Yetkin; Zabi, Alexandre; Zghiche, Amina; Agram, Jean-Laurent; Andrea, Jeremy; Bloch, Daniel; Brom, Jean-Marie; Buttignol, Michael; Chabert, Eric Christian; Chanon, Nicolas; Collard, Caroline; Conte, Eric; Coubez, Xavier; Fontaine, Jean-Charles; Gelé, Denis; Goerlach, Ulrich; Jansová, Markéta; Le Bihan, Anne-Catherine; Tonon, Nicolas; Van Hove, Pierre; Gadrat, Sébastien; Beauceron, Stephanie; Bernet, Colin; Boudoul, Gaelle; Chierici, Roberto; Contardo, Didier; Depasse, Pierre; El Mamouni, Houmani; Fay, Jean; Finco, Linda; Gascon, Susan; Gouzevitch, Maxime; Grenier, Gérald; Ille, Bernard; Lagarde, Francois; Laktineh, Imad Baptiste; Lethuillier, Morgan; Mirabito, Laurent; Pequegnot, Anne-Laure; Perries, Stephane; Popov, Andrey; Sordini, Viola; Vander Donckt, Muriel; Viret, Sébastien; Toriashvili, Tengizi; Lomidze, David; Autermann, Christian; Beranek, Sarah; Feld, Lutz; Kiesel, Maximilian Knut; Klein, Katja; Lipinski, Martin; Preuten, Marius; Schomakers, Christian; Schulz, Johannes; Verlage, Tobias; Albert, Andreas; Dietz-Laursonn, Erik; Duchardt, Deborah; Endres, Matthias; Erdmann, Martin; Erdweg, Sören; Esch, Thomas; Fischer, Robert; Güth, Andreas; Hamer, Matthias; Hebbeker, Thomas; Heidemann, Carsten; Hoepfner, Kerstin; Knutzen, Simon; Merschmeyer, Markus; Meyer, Arnd; Millet, Philipp; Mukherjee, Swagata; Olschewski, Mark; Padeken, Klaas; Pook, Tobias; Radziej, Markus; Reithler, Hans; Rieger, Marcel; Scheuch, Florian; Teyssier, Daniel; Thüer, Sebastian; Flügge, Günter; Kargoll, Bastian; Kress, Thomas; Künsken, Andreas; Lingemann, Joschka; Müller, Thomas; Nehrkorn, Alexander; Nowack, Andreas; Pistone, Claudia; Pooth, Oliver; Stahl, Achim; Aldaya Martin, Maria; Arndt, Till; Asawatangtrakuldee, Chayanit; Beernaert, Kelly; Behnke, Olaf; Behrens, Ulf; Bermúdez Martínez, Armando; Bin Anuar, Afiq Aizuddin; Borras, Kerstin; Botta, Valeria; Campbell, Alan; Connor, Patrick; Contreras-Campana, Christian; Costanza, Francesco; Diez Pardos, Carmen; Eckerlin, Guenter; Eckstein, Doris; Eichhorn, Thomas; Eren, Engin; Gallo, Elisabetta; Garay Garcia, Jasone; Geiser, Achim; Gizhko, Andrii; Grados Luyando, Juan Manuel; Grohsjean, Alexander; Gunnellini, Paolo; Harb, Ali; Hauk, Johannes; Hempel, Maria; Jung, Hannes; Kalogeropoulos, Alexis; Kasemann, Matthias; Keaveney, James; Kleinwort, Claus; Korol, Ievgen; Krücker, Dirk; Lange, Wolfgang; Lelek, Aleksandra; Lenz, Teresa; Leonard, Jessica; Lipka, Katerina; Lohmann, Wolfgang; Mankel, Rainer; Melzer-Pellmann, Isabell-Alissandra; Meyer, Andreas Bernhard; Mittag, Gregor; Mnich, Joachim; Mussgiller, Andreas; Ntomari, Eleni; Pitzl, Daniel; Raspereza, Alexei; Roland, Benoit; Savitskyi, Mykola; Saxena, Pooja; Shevchenko, Rostyslav; Spannagel, Simon; Stefaniuk, Nazar; Van Onsem, Gerrit Patrick; Walsh, Roberval; Wen, Yiwen; Wichmann, Katarzyna; Wissing, Christoph; Zenaiev, Oleksandr; Bein, Samuel; Blobel, Volker; Centis Vignali, Matteo; Dreyer, Torben; Garutti, Erika; Gonzalez, Daniel; Haller, Johannes; Hinzmann, Andreas; Hoffmann, Malte; Karavdina, Anastasia; Klanner, Robert; Kogler, Roman; Kovalchuk, Nataliia; Kurz, Simon; Lapsien, Tobias; Marchesini, Ivan; Marconi, Daniele; Meyer, Mareike; Niedziela, Marek; Nowatschin, Dominik; Pantaleo, Felice; Peiffer, Thomas; Perieanu, Adrian; Scharf, Christian; Schleper, Peter; Schmidt, Alexander; Schumann, Svenja; Schwandt, Joern; Sonneveld, Jory; Stadie, Hartmut; Steinbrück, Georg; Stober, Fred-Markus Helmut; Stöver, Marc; Tholen, Heiner; Troendle, Daniel; Usai, Emanuele; Vanelderen, Lukas; Vanhoefer, Annika; Vormwald, Benedikt; Akbiyik, Melike; Barth, Christian; Baur, Sebastian; Butz, Erik; Caspart, René; Chwalek, Thorsten; Colombo, Fabio; De Boer, Wim; Dierlamm, Alexander; Freund, Benedikt; Friese, Raphael; Giffels, Manuel; Gilbert, Andrew; Haitz, Dominik; Hartmann, Frank; Heindl, Stefan Michael; Husemann, Ulrich; Kassel, Florian; Kudella, Simon; Mildner, Hannes; Mozer, Matthias Ulrich; Müller, Thomas; Plagge, Michael; Quast, Gunter; Rabbertz, Klaus; Schröder, Matthias; Shvetsov, Ivan; Sieber, Georg; Simonis, Hans-Jürgen; Ulrich, Ralf; Wayand, Stefan; Weber, Marc; Weiler, Thomas; Williamson, Shawn; Wöhrmann, Clemens; Wolf, Roger; Anagnostou, Georgios; Daskalakis, Georgios; Geralis, Theodoros; Giakoumopoulou, Viktoria Athina; Kyriakis, Aristotelis; Loukas, Demetrios; Topsis-Giotis, Iasonas; Karathanasis, George; Kesisoglou, Stilianos; Panagiotou, Apostolos; Saoulidou, Niki; Evangelou, Ioannis; Foudas, Costas; Kokkas, Panagiotis; Mallios, Stavros; Manthos, Nikolaos; Papadopoulos, Ioannis; Paradas, Evangelos; Strologas, John; Triantis, Frixos A; Csanad, Mate; Filipovic, Nicolas; Pasztor, Gabriella; Bencze, Gyorgy; Hajdu, Csaba; Horvath, Dezso; Hunyadi, Ádám; Sikler, Ferenc; Veszpremi, Viktor; Vesztergombi, Gyorgy; Zsigmond, Anna Julia; Beni, Noemi; Czellar, Sandor; Karancsi, János; Makovec, Alajos; Molnar, Jozsef; Szillasi, Zoltan; Bartók, Márton; Raics, Peter; Trocsanyi, Zoltan Laszlo; Ujvari, Balazs; Choudhury, Somnath; Komaragiri, Jyothsna Rani; Bahinipati, Seema; Bhowmik, Sandeep; Mal, Prolay; Mandal, Koushik; Nayak, Aruna; Sahoo, Deepak Kumar; Sahoo, Niladribihari; Swain, Sanjay Kumar; Bansal, Sunil; Beri, Suman Bala; Bhatnagar, Vipin; Chawla, Ridhi; Dhingra, Nitish; Kalsi, Amandeep Kaur; Kaur, Anterpreet; Kaur, Manjit; Kumar, Ramandeep; Kumari, Priyanka; Mehta, Ankita; Singh, Jasbir; Walia, Genius; Kumar, Ashok; Shah, Aashaq; Bhardwaj, Ashutosh; Chauhan, Sushil; Choudhary, Brajesh C; Garg, Rocky Bala; Keshri, Sumit; Kumar, Ajay; Malhotra, Shivali; Naimuddin, Md; Ranjan, Kirti; Sharma, Ramkrishna; Sharma, Varun; Bhardwaj, Rishika; Bhattacharya, Rajarshi; Bhattacharya, Satyaki; Bhawandeep, Bhawandeep; Dey, Sourav; Dutt, Suneel; Dutta, Suchandra; Ghosh, Shamik; Majumdar, Nayana; Modak, Atanu; Mondal, Kuntal; Mukhopadhyay, Supratik; Nandan, Saswati; Purohit, Arnab; Roy, Ashim; Roy, Debarati; Roy Chowdhury, Suvankar; Sarkar, Subir; Sharan, Manoj; Thakur, Shalini; Behera, Prafulla Kumar; Chudasama, Ruchi; Dutta, Dipanwita; Jha, Vishwajeet; Kumar, Vineet; Mohanty, Ajit Kumar; Netrakanti, Pawan Kumar; Pant, Lalit Mohan; Shukla, Prashant; Topkar, Anita; Aziz, Tariq; Dugad, Shashikant; Mahakud, Bibhuprasad; Mitra, Soureek; Mohanty, Gagan Bihari; Sur, Nairit; Sutar, Bajrang; Banerjee, Sudeshna; Bhattacharya, Soham; Chatterjee, Suman; Das, Pallabi; Guchait, Monoranjan; Jain, Sandhya; Kumar, Sanjeev; Maity, Manas; Majumder, Gobinda; Mazumdar, Kajari; Sarkar, Tanmay; Wickramage, Nadeesha; Chauhan, Shubhanshu; Dube, Sourabh; Hegde, Vinay; Kapoor, Anshul; Kothekar, Kunal; Pandey, Shubham; Rane, Aditee; Sharma, Seema; Chenarani, Shirin; Eskandari Tadavani, Esmaeel; Etesami, Seyed Mohsen; Khakzad, Mohsen; Mohammadi Najafabadi, Mojtaba; Naseri, Mohsen; Paktinat Mehdiabadi, Saeid; Rezaei Hosseinabadi, Ferdos; Safarzadeh, Batool; Zeinali, Maryam; Felcini, Marta; Grunewald, Martin; Abbrescia, Marcello; Calabria, Cesare; Caputo, Claudio; Colaleo, Anna; Creanza, Donato; Cristella, Leonardo; De Filippis, Nicola; De Palma, Mauro; Errico, Filippo; Fiore, Luigi; Iaselli, Giuseppe; Lezki, Samet; Maggi, Giorgio; Maggi, Marcello; Miniello, Giorgia; My, Salvatore; Nuzzo, Salvatore; Pompili, Alexis; Pugliese, Gabriella; Radogna, Raffaella; Ranieri, Antonio; Selvaggi, Giovanna; Sharma, Archana; Silvestris, Lucia; Venditti, Rosamaria; Verwilligen, Piet; Abbiendi, Giovanni; Battilana, Carlo; Bonacorsi, Daniele; Braibant-Giacomelli, Sylvie; Campanini, Renato; Capiluppi, Paolo; Castro, Andrea; Cavallo, Francesca Romana; Chhibra, Simranjit Singh; Codispoti, Giuseppe; Cuffiani, Marco; Dallavalle, Gaetano-Marco; Fabbri, Fabrizio; Fanfani, Alessandra; Fasanella, Daniele; Giacomelli, Paolo; Grandi, Claudio; Guiducci, Luigi; Marcellini, Stefano; Masetti, Gianni; Montanari, Alessandro; Navarria, Francesco; Perrotta, Andrea; Rossi, Antonio; Rovelli, Tiziano; Siroli, Gian Piero; Tosi, Nicolò; Albergo, Sebastiano; Costa, Salvatore; Di Mattia, Alessandro; Giordano, Ferdinando; Potenza, Renato; Tricomi, Alessia; Tuve, Cristina; Barbagli, Giuseppe; Chatterjee, Kalyanmoy; Ciulli, Vitaliano; Civinini, Carlo; D'Alessandro, Raffaello; Focardi, Ettore; Lenzi, Piergiulio; Meschini, Marco; Paoletti, Simone; Russo, Lorenzo; Sguazzoni, Giacomo; Strom, Derek; Viliani, Lorenzo; Benussi, Luigi; Bianco, Stefano; Fabbri, Franco; Piccolo, Davide; Primavera, Federica; Biggio, Carla; Calvelli, Valerio; Ferro, Fabrizio; Robutti, Enrico; Tosi, Silvano; Brianza, Luca; Brivio, Francesco; Ciriolo, Vincenzo; Dinardo, Mauro Emanuele; Fiorendi, Sara; Gennai, Simone; Ghezzi, Alessio; Govoni, Pietro; Malberti, Martina; Malvezzi, Sandra; Manzoni, Riccardo Andrea; Menasce, Dario; Moroni, Luigi; Paganoni, Marco; Pauwels, Kristof; Pedrini, Daniele; Pigazzini, Simone; Ragazzi, Stefano; Tabarelli de Fatis, Tommaso; Buontempo, Salvatore; Cavallo, Nicola; Di Guida, Salvatore; Fabozzi, Francesco; Fienga, Francesco; Iorio, Alberto Orso Maria; Khan, Wajid Ali; Lista, Luca; Meola, Sabino; Paolucci, Pierluigi; Sciacca, Crisostomo; Thyssen, Filip; Azzi, Patrizia; Bacchetta, Nicola; Benato, Lisa; Bisello, Dario; Boletti, Alessio; Carlin, Roberto; Carvalho Antunes De Oliveira, Alexandra; Checchia, Paolo; De Castro Manzano, Pablo; Dorigo, Tommaso; Gasparini, Fabrizio; Gasparini, Ugo; Gozzelino, Andrea; Lacaprara, Stefano; Lujan, Paul; Margoni, Martino; Meneguzzo, Anna Teresa; Pozzobon, Nicola; Ronchese, Paolo; Rossin, Roberto; Simonetto, Franco; Torassa, Ezio; Zanetti, Marco; Zotto, Pierluigi; Zumerle, Gianni; Braghieri, Alessandro; Fallavollita, Francesco; Magnani, Alice; Montagna, Paolo; Ratti, Sergio P; Re, Valerio; Ressegotti, Martina; Riccardi, Cristina; Salvini, Paola; Vai, Ilaria; Vitulo, Paolo; Alunni Solestizi, Luisa; Biasini, Maurizio; Bilei, Gian Mario; Cecchi, Claudia; Ciangottini, Diego; Fanò, Livio; Lariccia, Paolo; Leonardi, Roberto; Manoni, Elisa; Mantovani, Giancarlo; Mariani, Valentina; Menichelli, Mauro; Rossi, Alessandro; Santocchia, Attilio; Spiga, Daniele; Androsov, Konstantin; Azzurri, Paolo; Bagliesi, Giuseppe; Bernardini, Jacopo; Boccali, Tommaso; Borrello, Laura; Castaldi, Rino; Ciocci, Maria Agnese; Dell'Orso, Roberto; Fedi, Giacomo; Giannini, Leonardo; Giassi, Alessandro; Grippo, Maria Teresa; Ligabue, Franco; Lomtadze, Teimuraz; Manca, Elisabetta; Mandorli, Giulio; Martini, Luca; Messineo, Alberto; Palla, Fabrizio; Rizzi, Andrea; Savoy-Navarro, Aurore; Spagnolo, Paolo; Tenchini, Roberto; Tonelli, Guido; Venturi, Andrea; Verdini, Piero Giorgio; Barone, Luciano; Cavallari, Francesca; Cipriani, Marco; Daci, Nadir; Del Re, Daniele; Diemoz, Marcella; Gelli, Simone; Longo, Egidio; Margaroli, Fabrizio; Marzocchi, Badder; Meridiani, Paolo; Organtini, Giovanni; Paramatti, Riccardo; Preiato, Federico; Rahatlou, Shahram; Rovelli, Chiara; Santanastasio, Francesco; Amapane, Nicola; Arcidiacono, Roberta; Argiro, Stefano; Arneodo, Michele; Bartosik, Nazar; Bellan, Riccardo; Biino, Cristina; Cartiglia, Nicolo; Cenna, Francesca; Costa, Marco; Covarelli, Roberto; Degano, Alessandro; Demaria, Natale; Kiani, Bilal; Mariotti, Chiara; Maselli, Silvia; Migliore, Ernesto; Monaco, Vincenzo; Monteil, Ennio; Monteno, Marco; Obertino, Maria Margherita; Pacher, Luca; Pastrone, Nadia; Pelliccioni, Mario; Pinna Angioni, Gian Luca; Ravera, Fabio; Romero, Alessandra; Ruspa, Marta; Sacchi, Roberto; Shchelina, Ksenia; Sola, Valentina; Solano, Ada; Staiano, Amedeo; Traczyk, Piotr; Belforte, Stefano; Casarsa, Massimo; Cossutti, Fabio; Della Ricca, Giuseppe; Zanetti, Anna; Kim, Dong Hee; Kim, Gui Nyun; Kim, Min Suk; Lee, Jeongeun; Lee, Sangeun; Lee, Seh Wook; Moon, Chang-Seong; Oh, Young Do; Sekmen, Sezen; Son, Dong-Chul; Yang, Yu Chul; Lee, Ari; Kim, Hyunchul; Moon, Dong Ho; Oh, Geonhee; Brochero Cifuentes, Javier Andres; Goh, Junghwan; Kim, Tae Jeong; Cho, Sungwoong; Choi, Suyong; Go, Yeonju; Gyun, Dooyeon; Ha, Seungkyu; Hong, Byung-Sik; Jo, Youngkwon; Kim, Yongsun; Lee, Kisoo; Lee, Kyong Sei; Lee, Songkyo; Lim, Jaehoon; Park, Sung Keun; Roh, Youn; Almond, John; Kim, Junho; Kim, Jae Sung; Lee, Haneol; Lee, Kyeongpil; Nam, Kyungwook; Oh, Sung Bin; Radburn-Smith, Benjamin Charles; Seo, Seon-hee; Yang, Unki; Yoo, Hwi Dong; Yu, Geum Bong; Choi, Minkyoo; Kim, Hyunyong; Kim, Ji Hyun; Lee, Jason Sang Hun; Park, Inkyu; Ryu, Geonmo; Choi, Young-Il; Hwang, Chanwook; Lee, Jongseok; Yu, Intae; Dudenas, Vytautas; Juodagalvis, Andrius; Vaitkus, Juozas; Ahmed, Ijaz; Ibrahim, Zainol Abidin; Md Ali, Mohd Adli Bin; Mohamad Idris, Faridah; Wan Abdullah, Wan Ahmad Tajuddin; Yusli, Mohd Nizam; Zolkapli, Zukhaimira; Reyes-Almanza, Rogelio; Ramirez-Sanchez, Gabriel; Duran-Osuna, Cecilia; Castilla-Valdez, Heriberto; De La Cruz-Burelo, Eduard; Heredia-De La Cruz, Ivan; Rabadán-Trejo, Raúl Iraq; Lopez-Fernandez, Ricardo; Mejia Guisao, Jhovanny; Sánchez Hernández, Alberto; Carrillo Moreno, Salvador; Oropeza Barrera, Cristina; Vazquez Valencia, Fabiola; Pedraza, Isabel; Salazar Ibarguen, Humberto Antonio; Uribe Estrada, Cecilia; Morelos Pineda, Antonio; Krofcheck, David; Butler, Philip H; Ahmad, Ashfaq; Ahmad, Muhammad; Hassan, Qamar; Hoorani, Hafeez R; Saddique, Asif; Shah, Mehar Ali; Shoaib, Muhammad; Waqas, Muhammad; Bialkowska, Helena; Bluj, Michal; Boimska, Bozena; Frueboes, Tomasz; Górski, Maciej; Kazana, Malgorzata; Nawrocki, Krzysztof; Romanowska-Rybinska, Katarzyna; Szleper, Michal; Zalewski, Piotr; Bunkowski, Karol; Byszuk, Adrian; Doroba, Krzysztof; Kalinowski, Artur; Konecki, Marcin; Krolikowski, Jan; Misiura, Maciej; Olszewski, Michal; Pyskir, Andrzej; Walczak, Marek; Bargassa, Pedrame; Beirão Da Cruz E Silva, Cristóvão; Calpas, Betty; Di Francesco, Agostino; Faccioli, Pietro; Gallinaro, Michele; Hollar, Jonathan; Leonardo, Nuno; Lloret Iglesias, Lara; Nemallapudi, Mythra Varun; Seixas, Joao; Toldaiev, Oleksii; Vadruccio, Daniele; Varela, Joao; Afanasiev, Serguei; Bunin, Pavel; Gavrilenko, Mikhail; Golutvin, Igor; Gorbunov, Ilya; Kamenev, Alexey; Karjavin, Vladimir; Lanev, Alexander; Malakhov, Alexander; Matveev, Viktor; Palichik, Vladimir; Perelygin, Victor; Shmatov, Sergey; Shulha, Siarhei; Skatchkov, Nikolai; Smirnov, Vitaly; Voytishin, Nikolay; Zarubin, Anatoli; Ivanov, Yury; Kim, Victor; Kuznetsova, Ekaterina; Levchenko, Petr; Murzin, Victor; Oreshkin, Vadim; Smirnov, Igor; Sulimov, Valentin; Uvarov, Lev; Vavilov, Sergey; Vorobyev, Alexey; Andreev, Yuri; Dermenev, Alexander; Gninenko, Sergei; Golubev, Nikolai; Karneyeu, Anton; Kirsanov, Mikhail; Krasnikov, Nikolai; Pashenkov, Anatoli; Tlisov, Danila; Toropin, Alexander; Epshteyn, Vladimir; Gavrilov, Vladimir; Lychkovskaya, Natalia; Popov, Vladimir; Pozdnyakov, Ivan; Safronov, Grigory; Spiridonov, Alexander; Stepennov, Anton; Toms, Maria; Vlasov, Evgueni; Zhokin, Alexander; Aushev, Tagir; Bylinkin, Alexander; Chistov, Ruslan; Danilov, Mikhail; Parygin, Pavel; Philippov, Dmitry; Polikarpov, Sergey; Tarkovskii, Evgenii; Andreev, Vladimir; Azarkin, Maksim; Dremin, Igor; Kirakosyan, Martin; Terkulov, Adel; Baskakov, Alexey; Belyaev, Andrey; Boos, Edouard; Dubinin, Mikhail; Dudko, Lev; Ershov, Alexander; Gribushin, Andrey; Klyukhin, Vyacheslav; Kodolova, Olga; Lokhtin, Igor; Miagkov, Igor; Obraztsov, Stepan; Petrushanko, Sergey; Savrin, Viktor; Snigirev, Alexander; Blinov, Vladimir; Skovpen, Yuri; Shtol, Dmitry; Azhgirey, Igor; Bayshev, Igor; Bitioukov, Sergei; Elumakhov, Dmitry; Kachanov, Vassili; Kalinin, Alexey; Konstantinov, Dmitri; Krychkine, Victor; Petrov, Vladimir; Ryutin, Roman; Sobol, Andrei; Troshin, Sergey; Tyurin, Nikolay; Uzunian, Andrey; Volkov, Alexey; Adzic, Petar; Cirkovic, Predrag; Devetak, Damir; Dordevic, Milos; Milosevic, Jovan; Rekovic, Vladimir; Alcaraz Maestre, Juan; Barrio Luna, Mar; Cerrada, Marcos; Colino, Nicanor; De La Cruz, Begona; Delgado Peris, Antonio; Escalante Del Valle, Alberto; Fernandez Bedoya, Cristina; Fernández Ramos, Juan Pablo; Flix, Jose; Fouz, Maria Cruz; Garcia-Abia, Pablo; Gonzalez Lopez, Oscar; Goy Lopez, Silvia; Hernandez, Jose M; Josa, Maria Isabel; Pérez-Calero Yzquierdo, Antonio María; Puerta Pelayo, Jesus; Quintario Olmeda, Adrián; Redondo, Ignacio; Romero, Luciano; Senghi Soares, Mara; Álvarez Fernández, Adrian; de Trocóniz, Jorge F; Missiroli, Marino; Moran, Dermot; Cuevas, Javier; Erice, Carlos; Fernandez Menendez, Javier; Gonzalez Caballero, Isidro; González Fernández, Juan Rodrigo; Palencia Cortezon, Enrique; Sanchez Cruz, Sergio; Suárez Andrés, Ignacio; Vischia, Pietro; Vizan Garcia, Jesus Manuel; Cabrillo, Iban Jose; Calderon, Alicia; Chazin Quero, Barbara; Curras, Esteban; Duarte Campderros, Jordi; Fernandez, Marcos; Garcia-Ferrero, Juan; Gomez, Gervasio; Lopez Virto, Amparo; Marco, Jesus; Martinez Rivero, Celso; Martinez Ruiz del Arbol, Pablo; Matorras, Francisco; Piedra Gomez, Jonatan; Rodrigo, Teresa; Ruiz-Jimeno, Alberto; Scodellaro, Luca; Trevisani, Nicolò; Vila, Ivan; Vilar Cortabitarte, Rocio; Abbaneo, Duccio; Auffray, Etiennette; Baillon, Paul; Ball, Austin; Barney, David; Bianco, Michele; Bloch, Philippe; Bocci, Andrea; Botta, Cristina; Camporesi, Tiziano; Castello, Roberto; Cepeda, Maria; Cerminara, Gianluca; Chapon, Emilien; Chen, Yi; D'Enterria, David; Dabrowski, Anne; Daponte, Vincenzo; David Tinoco Mendes, Andre; De Gruttola, Michele; De Roeck, Albert; Di Marco, Emanuele; Dobson, Marc; Dorney, Brian; Du Pree, Tristan; Dünser, Marc; Dupont, Niels; Elliott-Peisert, Anna; Everaerts, Pieter; Franzoni, Giovanni; Fulcher, Jonathan; Funk, Wolfgang; Gigi, Dominique; Gill, Karl; Glege, Frank; Gulhan, Doga; Gundacker, Stefan; Guthoff, Moritz; Harris, Philip; Hegeman, Jeroen; Innocente, Vincenzo; Janot, Patrick; Karacheban, Olena; Kieseler, Jan; Kirschenmann, Henning; Knünz, Valentin; Kornmayer, Andreas; Kortelainen, Matti J; Krammer, Manfred; Lange, Clemens; Lecoq, Paul; Lourenco, Carlos; Lucchini, Marco Toliman; Malgeri, Luca; Mannelli, Marcello; Martelli, Arabella; Meijers, Frans; Merlin, Jeremie Alexandre; Mersi, Stefano; Meschi, Emilio; Milenovic, Predrag; Moortgat, Filip; Mulders, Martijn; Neugebauer, Hannes; Orfanelli, Styliani; Orsini, Luciano; Pape, Luc; Perez, Emmanuel; Peruzzi, Marco; Petrilli, Achille; Petrucciani, Giovanni; Pfeiffer, Andreas; Pierini, Maurizio; Racz, Attila; Reis, Thomas; Rolandi, Gigi; Rovere, Marco; Sakulin, Hannes; Schäfer, Christoph; Schwick, Christoph; Seidel, Markus; Selvaggi, Michele; Sharma, Archana; Silva, Pedro; Sphicas, Paraskevas; Stakia, Anna; Steggemann, Jan; Stoye, Markus; Tosi, Mia; Treille, Daniel; Triossi, Andrea; Tsirou, Andromachi; Veckalns, Viesturs; Veres, Gabor Istvan; Verweij, Marta; Wardle, Nicholas; Zeuner, Wolfram Dietrich; Bertl, Willi; Caminada, Lea; Deiters, Konrad; Erdmann, Wolfram; Horisberger, Roland; Ingram, Quentin; Kaestli, Hans-Christian; Kotlinski, Danek; Langenegger, Urs; Rohe, Tilman; Wiederkehr, Stephan Albert; Bachmair, Felix; Bäni, Lukas; Berger, Pirmin; Bianchini, Lorenzo; Casal, Bruno; Dissertori, Günther; Dittmar, Michael; Donegà, Mauro; Grab, Christoph; Heidegger, Constantin; Hits, Dmitry; Hoss, Jan; Kasieczka, Gregor; Klijnsma, Thomas; Lustermann, Werner; Mangano, Boris; Marionneau, Matthieu; Meinhard, Maren Tabea; Meister, Daniel; Micheli, Francesco; Musella, Pasquale; Nessi-Tedaldi, Francesca; Pandolfi, Francesco; Pata, Joosep; Pauss, Felicitas; Perrin, Gaël; Perrozzi, Luca; Quittnat, Milena; Reichmann, Michael; Schönenberger, Myriam; Shchutska, Lesya; Tavolaro, Vittorio Raoul; Theofilatos, Konstantinos; Vesterbacka Olsson, Minna Leonora; Wallny, Rainer; Zhu, De Hua; Aarrestad, Thea Klaeboe; Amsler, Claude; Canelli, Maria Florencia; De Cosa, Annapaola; Del Burgo, Riccardo; Donato, Silvio; Galloni, Camilla; Hreus, Tomas; Kilminster, Benjamin; Ngadiuba, Jennifer; Pinna, Deborah; Rauco, Giorgia; Robmann, Peter; Salerno, Daniel; Seitz, Claudia; Takahashi, Yuta; Zucchetta, Alberto; Candelise, Vieri; Doan, Thi Hien; Jain, Shilpi; Khurana, Raman; Kuo, Chia-Ming; Lin, Willis; Pozdnyakov, Andrey; Yu, Shin-Shan; Kumar, Arun; Chang, Paoti; Chao, Yuan; Chen, Kai-Feng; Chen, Po-Hsun; Fiori, Francesco; Hou, George Wei-Shu; Hsiung, Yee; Liu, Yueh-Feng; Lu, Rong-Shyang; Paganis, Efstathios; Psallidas, Andreas; Steen, Arnaud; Tsai, Jui-fa; Asavapibhop, Burin; Kovitanggoon, Kittikul; Singh, Gurpreet; Srimanobhas, Norraphat; Adiguzel, Aytul; Boran, Fatma; Cerci, Salim; Damarseckin, Serdal; Demiroglu, Zuhal Seyma; Dozen, Candan; Dumanoglu, Isa; Girgis, Semiray; Gokbulut, Gul; Guler, Yalcin; Hos, Ilknur; Kangal, Evrim Ersin; Kara, Ozgun; Kayis Topaksu, Aysel; Kiminsu, Ugur; Oglakci, Mehmet; Onengut, Gulsen; Ozdemir, Kadri; Sunar Cerci, Deniz; Tali, Bayram; Turkcapar, Semra; Zorbakir, Ibrahim Soner; Zorbilmez, Caglar; Bilin, Bugra; Karapinar, Guler; Ocalan, Kadir; Yalvac, Metin; Zeyrek, Mehmet; Gülmez, Erhan; Kaya, Mithat; Kaya, Ozlem; Tekten, Sevgi; Yetkin, Elif Asli; Nazlim Agaras, Merve; Atay, Serhat; Cakir, Altan; Cankocak, Kerem; Grynyov, Boris; Levchuk, Leonid; Sorokin, Pavel; Aggleton, Robin; Ball, Fionn; Beck, Lana; Brooke, James John; Burns, Douglas; Clement, Emyr; Cussans, David; Davignon, Olivier; Flacher, Henning; Goldstein, Joel; Grimes, Mark; Heath, Greg P; Heath, Helen F; Jacob, Jeson; Kreczko, Lukasz; Lucas, Chris; Newbold, Dave M; Paramesvaran, Sudarshan; Poll, Anthony; Sakuma, Tai; Seif El Nasr-storey, Sarah; Smith, Dominic; Smith, Vincent J; Bell, Ken W; Belyaev, Alexander; Brew, Christopher; Brown, Robert M; Calligaris, Luigi; Cieri, Davide; Cockerill, David JA; Coughlan, John A; Harder, Kristian; Harper, Sam; Olaiya, Emmanuel; Petyt, David; Shepherd-Themistocleous, Claire; Thea, Alessandro; Tomalin, Ian R; Williams, Thomas; Auzinger, Georg; Bainbridge, Robert; Breeze, Shane; Buchmuller, Oliver; Bundock, Aaron; Casasso, Stefano; Citron, Matthew; Colling, David; Corpe, Louie; Dauncey, Paul; Davies, Gavin; De Wit, Adinda; Della Negra, Michel; Di Maria, Riccardo; Elwood, Adam; Haddad, Yacine; Hall, Geoffrey; Iles, Gregory; James, Thomas; Lane, Rebecca; Laner, Christian; Lyons, Louis; Magnan, Anne-Marie; Malik, Sarah; Mastrolorenzo, Luca; Matsushita, Takashi; Nash, Jordan; Nikitenko, Alexander; Palladino, Vito; Pesaresi, Mark; Raymond, David Mark; Richards, Alexander; Rose, Andrew; Scott, Edward; Seez, Christopher; Shtipliyski, Antoni; Summers, Sioni; Tapper, Alexander; Uchida, Kirika; Vazquez Acosta, Monica; Virdee, Tejinder; Winterbottom, Daniel; Wright, Jack; Zenz, Seth Conrad; Cole, Joanne; Hobson, Peter R; Khan, Akram; Kyberd, Paul; Reid, Ivan; Symonds, Philip; Teodorescu, Liliana; Turner, Mark; Borzou, Ahmad; Call, Kenneth; Dittmann, Jay; Hatakeyama, Kenichi; Liu, Hongxuan; Pastika, Nathaniel; Smith, Caleb; Bartek, Rachel; Dominguez, Aaron; Buccilli, Andrew; Cooper, Seth; Henderson, Conor; Rumerio, Paolo; West, Christopher; Arcaro, Daniel; Avetisyan, Aram; Bose, Tulika; Gastler, Daniel; Rankin, Dylan; Richardson, Clint; Rohlf, James; Sulak, Lawrence; Zou, David; Benelli, Gabriele; Cutts, David; Garabedian, Alex; Hakala, John; Heintz, Ulrich; Hogan, Julie Managan; Kwok, Ka Hei Martin; Laird, Edward; Landsberg, Greg; Mao, Zaixing; Narain, Meenakshi; Pazzini, Jacopo; Piperov, Stefan; Sagir, Sinan; Syarif, Rizki; Yu, David; Band, Reyer; Brainerd, Christopher; Burns, Dustin; Calderon De La Barca Sanchez, Manuel; Chertok, Maxwell; Conway, John; Conway, Rylan; Cox, Peter Timothy; Erbacher, Robin; Flores, Chad; Funk, Garrett; Gardner, Michael; Ko, Winston; Lander, Richard; Mclean, Christine; Mulhearn, Michael; Pellett, Dave; Pilot, Justin; Shalhout, Shalhout; Shi, Mengyao; Smith, John; Squires, Michael; Stolp, Dustin; Tos, Kyle; Tripathi, Mani; Wang, Zhangqier; Bachtis, Michail; Bravo, Cameron; Cousins, Robert; Dasgupta, Abhigyan; Florent, Alice; Hauser, Jay; Ignatenko, Mikhail; Mccoll, Nickolas; Saltzberg, David; Schnaible, Christian; Valuev, Vyacheslav; Bouvier, Elvire; Burt, Kira; Clare, Robert; Ellison, John Anthony; Gary, J William; Ghiasi Shirazi, Seyyed Mohammad Amin; Hanson, Gail; Heilman, Jesse; Jandir, Pawandeep; Kennedy, Elizabeth; Lacroix, Florent; Long, Owen Rosser; Olmedo Negrete, Manuel; Paneva, Mirena Ivova; Shrinivas, Amithabh; Si, Weinan; Wang, Long; Wei, Hua; Wimpenny, Stephen; Yates, Brent; Branson, James G; Cittolin, Sergio; Derdzinski, Mark; Gerosa, Raffaele; Hashemi, Bobak; Holzner, André; Klein, Daniel; Kole, Gouranga; Krutelyov, Vyacheslav; Letts, James; Macneill, Ian; Masciovecchio, Mario; Olivito, Dominick; Padhi, Sanjay; Pieri, Marco; Sani, Matteo; Sharma, Vivek; Simon, Sean; Tadel, Matevz; Vartak, Adish; Wasserbaech, Steven; Wood, John; Würthwein, Frank; Yagil, Avraham; Zevi Della Porta, Giovanni; Amin, Nick; Bhandari, Rohan; Bradmiller-Feld, John; Campagnari, Claudio; Dishaw, Adam; Dutta, Valentina; Franco Sevilla, Manuel; George, Christopher; Golf, Frank; Gouskos, Loukas; Gran, Jason; Heller, Ryan; Incandela, Joe; Mullin, Sam Daniel; Ovcharova, Ana; Qu, Huilin; Richman, Jeffrey; Stuart, David; Suarez, Indara; Yoo, Jaehyeok; Anderson, Dustin; Bendavid, Joshua; Bornheim, Adolf; Lawhorn, Jay Mathew; Newman, Harvey B; Nguyen, Thong; Pena, Cristian; Spiropulu, Maria; Vlimant, Jean-Roch; Xie, Si; Zhang, Zhicai; Zhu, Ren-Yuan; Andrews, Michael Benjamin; Ferguson, Thomas; Mudholkar, Tanmay; Paulini, Manfred; Russ, James; Sun, Menglei; Vogel, Helmut; Vorobiev, Igor; Weinberg, Marc; Cumalat, John Perry; Ford, William T; Jensen, Frank; Johnson, Andrew; Krohn, Michael; Leontsinis, Stefanos; Mulholland, Troy; Stenson, Kevin; Wagner, Stephen Robert; Alexander, James; Chaves, Jorge; Chu, Jennifer; Dittmer, Susan; Mcdermott, Kevin; Mirman, Nathan; Patterson, Juliet Ritchie; Rinkevicius, Aurelijus; Ryd, Anders; Skinnari, Louise; Soffi, Livia; Tan, Shao Min; Tao, Zhengcheng; Thom, Julia; Tucker, Jordan; Wittich, Peter; Zientek, Margaret; Abdullin, Salavat; Albrow, Michael; Apollinari, Giorgio; Apresyan, Artur; Apyan, Aram; Banerjee, Sunanda; Bauerdick, Lothar AT; Beretvas, Andrew; Berryhill, Jeffrey; Bhat, Pushpalatha C; Bolla, Gino; Burkett, Kevin; Butler, Joel Nathan; Canepa, Anadi; Cerati, Giuseppe Benedetto; Cheung, Harry; Chlebana, Frank; Cremonesi, Matteo; Duarte, Javier; Elvira, Victor Daniel; Freeman, Jim; Gecse, Zoltan; Gottschalk, Erik; Gray, Lindsey; Green, Dan; Grünendahl, Stefan; Gutsche, Oliver; Harris, Robert M; Hasegawa, Satoshi; Hirschauer, James; Hu, Zhen; Jayatilaka, Bodhitha; Jindariani, Sergo; Johnson, Marvin; Joshi, Umesh; Klima, Boaz; Kreis, Benjamin; Lammel, Stephan; Lincoln, Don; Lipton, Ron; Liu, Miaoyuan; Liu, Tiehui; Lopes De Sá, Rafael; Lykken, Joseph; Maeshima, Kaori; Magini, Nicolo; Marraffino, John Michael; Maruyama, Sho; Mason, David; McBride, Patricia; Merkel, Petra; Mrenna, Stephen; Nahn, Steve; O'Dell, Vivian; Pedro, Kevin; Prokofyev, Oleg; Rakness, Gregory; Ristori, Luciano; Schneider, Basil; Sexton-Kennedy, Elizabeth; Soha, Aron; Spalding, William J; Spiegel, Leonard; Stoynev, Stoyan; Strait, James; Strobbe, Nadja; Taylor, Lucas; Tkaczyk, Slawek; Tran, Nhan Viet; Uplegger, Lorenzo; Vaandering, Eric Wayne; Vernieri, Caterina; Verzocchi, Marco; Vidal, Richard; Wang, Michael; Weber, Hannsjoerg Artur; Whitbeck, Andrew; Acosta, Darin; Avery, Paul; Bortignon, Pierluigi; Bourilkov, Dimitri; Brinkerhoff, Andrew; Carnes, Andrew; Carver, Matthew; Curry, David; Field, Richard D; Furic, Ivan-Kresimir; Konigsberg, Jacobo; Korytov, Andrey; Kotov, Khristian; Ma, Peisen; Matchev, Konstantin; Mei, Hualin; Mitselmakher, Guenakh; Rank, Douglas; Sperka, David; Terentyev, Nikolay; Thomas, Laurent; Wang, Jian; Wang, Sean-Jiun; Yelton, John; Joshi, Yagya Raj; Linn, Stephan; Markowitz, Pete; Rodriguez, Jorge Luis; Ackert, Andrew; Adams, Todd; Askew, Andrew; Hagopian, Sharon; Hagopian, Vasken; Johnson, Kurtis F; Kolberg, Ted; Martinez, German; Perry, Thomas; Prosper, Harrison; Saha, Anirban; Santra, Arka; Yohay, Rachel; Baarmand, Marc M; Bhopatkar, Vallary; Colafranceschi, Stefano; Hohlmann, Marcus; Noonan, Daniel; Roy, Titas; Yumiceva, Francisco; Adams, Mark Raymond; Apanasevich, Leonard; Berry, Douglas; Betts, Russell Richard; Cavanaugh, Richard; Chen, Xuan; Evdokimov, Olga; Gerber, Cecilia Elena; Hangal, Dhanush Anil; Hofman, David Jonathan; Jung, Kurt; Kamin, Jason; Sandoval Gonzalez, Irving Daniel; Tonjes, Marguerite; Trauger, Hallie; Varelas, Nikos; Wang, Hui; Wu, Zhenbin; Zhang, Jingyu; Bilki, Burak; Clarida, Warren; Dilsiz, Kamuran; Durgut, Süleyman; Gandrajula, Reddy Pratap; Haytmyradov, Maksat; Khristenko, Viktor; Merlo, Jean-Pierre; Mermerkaya, Hamit; Mestvirishvili, Alexi; Moeller, Anthony; Nachtman, Jane; Ogul, Hasan; Onel, Yasar; Ozok, Ferhat; Penzo, Aldo; Snyder, Christina; Tiras, Emrah; Wetzel, James; Yi, Kai; Blumenfeld, Barry; Cocoros, Alice; Eminizer, Nicholas; Fehling, David; Feng, Lei; Gritsan, Andrei; Maksimovic, Petar; Roskes, Jeffrey; Sarica, Ulascan; Swartz, Morris; Xiao, Meng; You, Can; Al-bataineh, Ayman; Baringer, Philip; Bean, Alice; Boren, Samuel; Bowen, James; Castle, James; Khalil, Sadia; Kropivnitskaya, Anna; Majumder, Devdatta; Mcbrayer, William; Murray, Michael; Royon, Christophe; Sanders, Stephen; Schmitz, Erich; Stringer, Robert; Tapia Takaki, Daniel; Wang, Quan; Ivanov, Andrew; Kaadze, Ketino; Maravin, Yurii; Mohammadi, Abdollah; Saini, Lovedeep Kaur; Skhirtladze, Nikoloz; Toda, Sachiko; Rebassoo, Finn; Wright, Douglas; Anelli, Christopher; Baden, Drew; Baron, Owen; Belloni, Alberto; Calvert, Brian; Eno, Sarah Catherine; Ferraioli, Charles; Hadley, Nicholas John; Jabeen, Shabnam; Jeng, Geng-Yuan; Kellogg, Richard G; Kunkle, Joshua; Mignerey, Alice; Ricci-Tam, Francesca; Shin, Young Ho; Skuja, Andris; Tonwar, Suresh C; Abercrombie, Daniel; Allen, Brandon; Azzolini, Virginia; Barbieri, Richard; Baty, Austin; Bi, Ran; Brandt, Stephanie; Busza, Wit; Cali, Ivan Amos; D'Alfonso, Mariarosaria; Demiragli, Zeynep; Gomez Ceballos, Guillelmo; Goncharov, Maxim; Hsu, Dylan; Iiyama, Yutaro; Innocenti, Gian Michele; Klute, Markus; Kovalskyi, Dmytro; Lai, Yue Shi; Lee, Yen-Jie; Levin, Andrew; Luckey, Paul David; Maier, Benedikt; Marini, Andrea Carlo; Mcginn, Christopher; Mironov, Camelia; Narayanan, Siddharth; Niu, Xinmei; Paus, Christoph; Roland, Christof; Roland, Gunther; Salfeld-Nebgen, Jakob; Stephans, George; Tatar, Kaya; Velicanu, Dragos; Wang, Jing; Wang, Ta-Wei; Wyslouch, Bolek; Benvenuti, Alberto; Chatterjee, Rajdeep Mohan; Evans, Andrew; Hansen, Peter; Kalafut, Sean; Kubota, Yuichi; Lesko, Zachary; Mans, Jeremy; Nourbakhsh, Shervin; Ruckstuhl, Nicole; Rusack, Roger; Turkewitz, Jared; Acosta, John Gabriel; Oliveros, Sandra; Avdeeva, Ekaterina; Bloom, Kenneth; Claes, Daniel R; Fangmeier, Caleb; Gonzalez Suarez, Rebeca; Kamalieddin, Rami; Kravchenko, Ilya; Monroy, Jose; Siado, Joaquin Emilo; Snow, Gregory R; Stieger, Benjamin; Alyari, Maral; Dolen, James; Godshalk, Andrew; Harrington, Charles; Iashvili, Ia; Nguyen, Duong; Parker, Ashley; Rappoccio, Salvatore; Roozbahani, Bahareh; Alverson, George; Barberis, Emanuela; Hortiangtham, Apichart; Massironi, Andrea; Morse, David Michael; Nash, David; Orimoto, Toyoko; Teixeira De Lima, Rafael; Trocino, Daniele; Wood, Darien; Bhattacharya, Saptaparna; Charaf, Otman; Hahn, Kristan Allan; Mucia, Nicholas; Odell, Nathaniel; Pollack, Brian; Schmitt, Michael Henry; Sung, Kevin; Trovato, Marco; Velasco, Mayda; Dev, Nabarun; Hildreth, Michael; Hurtado Anampa, Kenyi; Jessop, Colin; Karmgard, Daniel John; Kellams, Nathan; Lannon, Kevin; Loukas, Nikitas; Marinelli, Nancy; Meng, Fanbo; Mueller, Charles; Musienko, Yuri; Planer, Michael; Reinsvold, Allison; Ruchti, Randy; Smith, Geoffrey; Taroni, Silvia; Wayne, Mitchell; Wolf, Matthias; Woodard, Anna; Alimena, Juliette; Antonelli, Louis; Bylsma, Ben; Durkin, Lloyd Stanley; Flowers, Sean; Francis, Brian; Hart, Andrew; Hill, Christopher; Ji, Weifeng; Liu, Bingxuan; Luo, Wuming; Puigh, Darren; Winer, Brian L; Wulsin, Howard Wells; Benaglia, Andrea; Cooperstein, Stephane; Driga, Olga; Elmer, Peter; Hardenbrook, Joshua; Hebda, Philip; Higginbotham, Samuel; Lange, David; Luo, Jingyu; Marlow, Daniel; Mei, Kelvin; Ojalvo, Isabel; Olsen, James; Palmer, Christopher; Piroué, Pierre; Stickland, David; Tully, Christopher; Malik, Sudhir; Norberg, Scarlet; Barker, Anthony; Barnes, Virgil E; Das, Souvik; Folgueras, Santiago; Gutay, Laszlo; Jha, Manoj; Jones, Matthew; Jung, Andreas Werner; Khatiwada, Ajeeta; Miller, David Harry; Neumeister, Norbert; Peng, Cheng-Chieh; Schulte, Jan-Frederik; Sun, Jian; Wang, Fuqiang; Xie, Wei; Cheng, Tongguang; Parashar, Neeti; Stupak, John; Adair, Antony; Akgun, Bora; Chen, Zhenyu; Ecklund, Karl Matthew; Geurts, Frank JM; Guilbaud, Maxime; Li, Wei; Michlin, Benjamin; Northup, Michael; Padley, Brian Paul; Roberts, Jay; Rorie, Jamal; Tu, Zhoudunming; Zabel, James; Bodek, Arie; de Barbaro, Pawel; Demina, Regina; Duh, Yi-ting; Ferbel, Thomas; Galanti, Mario; Garcia-Bellido, Aran; Han, Jiyeon; Hindrichs, Otto; Khukhunaishvili, Aleko; Lo, Kin Ho; Tan, Ping; Verzetti, Mauro; Ciesielski, Robert; Goulianos, Konstantin; Mesropian, Christina; Agapitos, Antonis; Chou, John Paul; Gershtein, Yuri; Gómez Espinosa, Tirso Alejandro; Halkiadakis, Eva; Heindl, Maximilian; Hughes, Elliot; Kaplan, Steven; Kunnawalkam Elayavalli, Raghav; Kyriacou, Savvas; Lath, Amitabh; Montalvo, Roy; Nash, Kevin; Osherson, Marc; Saka, Halil; Salur, Sevil; Schnetzer, Steve; Sheffield, David; Somalwar, Sunil; Stone, Robert; Thomas, Scott; Thomassen, Peter; Walker, Matthew; Delannoy, Andrés G; Foerster, Mark; Heideman, Joseph; Riley, Grant; Rose, Keith; Spanier, Stefan; Thapa, Krishna; Bouhali, Othmane; Castaneda Hernandez, Alfredo; Celik, Ali; Dalchenko, Mykhailo; De Mattia, Marco; Delgado, Andrea; Dildick, Sven; Eusebi, Ricardo; Gilmore, Jason; Huang, Tao; Kamon, Teruki; Mueller, Ryan; Pakhotin, Yuriy; Patel, Rishi; Perloff, Alexx; Perniè, Luca; Rathjens, Denis; Safonov, Alexei; Tatarinov, Aysen; Ulmer, Keith; Akchurin, Nural; Damgov, Jordan; De Guio, Federico; Dudero, Phillip Russell; Faulkner, James; Gurpinar, Emine; Kunori, Shuichi; Lamichhane, Kamal; Lee, Sung Won; Libeiro, Terence; Peltola, Timo; Undleeb, Sonaina; Volobouev, Igor; Wang, Zhixing; Greene, Senta; Gurrola, Alfredo; Janjam, Ravi; Johns, Willard; Maguire, Charles; Melo, Andrew; Ni, Hong; Sheldon, Paul; Tuo, Shengquan; Velkovska, Julia; Xu, Qiao; Arenton, Michael Wayne; Barria, Patrizia; Cox, Bradley; Hirosky, Robert; Ledovskoy, Alexander; Li, Hengne; Neu, Christopher; Sinthuprasith, Tutanon; Sun, Xin; Wang, Yanchu; Wolfe, Evan; Xia, Fan; Harr, Robert; Karchin, Paul Edmund; Sturdy, Jared; Zaleski, Shawn; Brodski, Michael; Buchanan, James; Caillol, Cécile; Dasu, Sridhara; Dodd, Laura; Duric, Senka; Gomber, Bhawna; Grothe, Monika; Herndon, Matthew; Hervé, Alain; Hussain, Usama; Klabbers, Pamela; Lanaro, Armando; Levine, Aaron; Long, Kenneth; Loveless, Richard; Pierro, Giuseppe Antonio; Polese, Giovanni; Ruggles, Tyler; Savin, Alexander; Smith, Nicholas; Smith, Wesley H; Taylor, Devin; Woods, Nathaniel

2017-12-01

A search for a signal consistent with the type-III seesaw mechanism in events with three or more electrons or muons is presented. The data sample consists of proton-proton collisions at $ \\sqrt{s} = $ 13 TeV collected by the CMS experiment at the LHC in 2016 and corresponds to an integrated luminosity of 35.9 fb$^{-1}$. Selection criteria based on the number of leptons and the invariant mass of opposite-sign lepton pairs are used to distinguish the signal from the standard model background. The observations are consistent with the expectations from standard model processes. The results are used to place limits on the production of heavy fermions of the type-III seesaw model as a function of the branching ratio to each lepton flavor. In the scenario of equal branching fractions to each lepton flavor, heavy fermions with masses below 840 GeV are excluded. This is the most sensitive probe to date of the type-III seesaw mechanism.

Search for Evidence of the Type-III Seesaw Mechanism in Multilepton Final States in Proton-Proton Collisions at √{s }=13 TeV

Science.gov (United States)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Ambrogi, F.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Grossmann, J.; Hrubec, J.; Jeitler, M.; König, A.; Krammer, N.; Krätschmer, I.; Liko, D.; Madlener, T.; Mikulec, I.; Pree, E.; Rabady, D.; Rad, N.; Rohringer, H.; Schieck, J.; Schöfbeck, R.; Spanring, M.; Spitzbart, D.; Waltenberger, W.; Wittmann, J.; Wulz, C.-E.; Zarucki, M.; Chekhovsky, V.; Mossolov, V.; Suarez Gonzalez, J.; De Wolf, E. A.; Di Croce, D.; Janssen, X.; Lauwers, J.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; De Bruyn, I.; De Clercq, J.; Deroover, K.; Flouris, G.; Lontkovskyi, D.; Lowette, S.; Moortgat, S.; Moreels, L.; Python, Q.; Skovpen, K.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Parijs, I.; Brun, H.; Clerbaux, B.; De Lentdecker, G.; Delannoy, H.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Luetic, J.; Maerschalk, T.; Marinov, A.; Randle-conde, A.; Seva, T.; Vander Velde, C.; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Zenoni, F.; Zhang, F.; Cimmino, A.; Cornelis, T.; Dobur, D.; Fagot, A.; Gul, M.; Khvastunov, I.; Poyraz, D.; Roskas, C.; Salva, S.; Tytgat, M.; Verbeke, W.; Zaganidis, N.; Bakhshiansohi, H.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; De Visscher, S.; Delaere, C.; Delcourt, M.; Francois, B.; Giammanco, A.; Jafari, A.; Komm, M.; Krintiras, G.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Musich, M.; Piotrzkowski, K.; Quertenmont, L.; Vidal Marono, M.; Wertz, S.; Beliy, N.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; Da Silveira, G. G.; De Jesus Damiao, D.; Fonseca De Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Melo De Almeida, M.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Torres Da Silva De Araujo, F.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; Tomei, T. R. Fernandez Perez; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Misheva, M.; Rodozov, M.; Shopova, M.; Stoykova, S.; Sultanov, G.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Fang, W.; Gao, X.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Chen, Y.; Jiang, C. H.; Leggat, D.; Liao, H.; Liu, Z.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Yazgan, E.; Zhang, H.; Zhao, J.; Ban, Y.; Chen, G.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; González Hernández, C. F.; Ruiz Alvarez, J. D.; Courbon, B.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Sculac, T.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Mesic, B.; Starodumov, A.; Susa, T.; Ather, M. W.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Finger, M.; Finger, M.; Carrera Jarrin, E.; El-khateeb, E.; Elgammal, S.; Ellithi Kamel, A.; Dewanjee, R. K.; Kadastik, M.; Perrini, L.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Faure, J. L.; Ferri, F.; Ganjour, S.; Ghosh, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Kucher, I.; Locci, E.; Machet, M.; Malcles, J.; Negro, G.; Rander, J.; Rosowsky, A.; Sahin, M. Ã.-.; Titov, M.; Abdulsalam, A.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Charlot, C.; Granier de Cassagnac, R.; Jo, M.; Lisniak, S.; Lobanov, A.; Martin Blanco, J.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Stahl Leiton, A. G.; Strebler, T.; Yilmaz, Y.; Zabi, A.; Zghiche, A.; Agram, J.-L.; Andrea, J.; Bloch, D.; Brom, J.-M.; Buttignol, M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Coubez, X.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Jansová, M.; Le Bihan, A.-C.; Tonon, N.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fay, J.; Finco, L.; Gascon, S.; Gouzevitch, M.; Grenier, G.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Popov, A.; Sordini, V.; Vander Donckt, M.; Viret, S.; Toriashvili, T.; Lomidze, D.; Autermann, C.; Beranek, S.; Feld, L.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Preuten, M.; Schomakers, C.; Schulz, J.; Verlage, T.; Albert, A.; Dietz-Laursonn, E.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hamer, M.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Knutzen, S.; Merschmeyer, M.; Meyer, A.; Millet, P.; Mukherjee, S.; Olschewski, M.; Padeken, K.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Teyssier, D.; Thüer, S.; Flügge, G.; Kargoll, B.; Kress, T.; Künsken, A.; Lingemann, J.; Müller, T.; Nehrkorn, A.; Nowack, A.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Arndt, T.; Asawatangtrakuldee, C.; Beernaert, K.; Behnke, O.; Behrens, U.; Bermúdez Martínez, A.; Bin Anuar, A. A.; Borras, K.; Botta, V.; Campbell, A.; Connor, P.; Contreras-Campana, C.; Costanza, F.; Diez Pardos, C.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Eren, E.; Gallo, E.; Garay Garcia, J.; Geiser, A.; Gizhko, A.; Grados Luyando, J. M.; Grohsjean, A.; Gunnellini, P.; Harb, A.; Hauk, J.; Hempel, M.; Jung, H.; Kalogeropoulos, A.; Kasemann, M.; Keaveney, J.; Kleinwort, C.; Korol, I.; Krücker, D.; Lange, W.; Lelek, A.; Lenz, T.; Leonard, J.; Lipka, K.; Lohmann, W.; Mankel, R.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Ntomari, E.; Pitzl, D.; Raspereza, A.; Roland, B.; Savitskyi, M.; Saxena, P.; Shevchenko, R.; Spannagel, S.; Stefaniuk, N.; Van Onsem, G. P.; Walsh, R.; Wen, Y.; Wichmann, K.; Wissing, C.; Zenaiev, O.; Bein, S.; Blobel, V.; Centis Vignali, M.; Dreyer, T.; Garutti, E.; Gonzalez, D.; Haller, J.; Hinzmann, A.; Hoffmann, M.; Karavdina, A.; Klanner, R.; Kogler, R.; Kovalchuk, N.; Kurz, S.; Lapsien, T.; Marchesini, I.; Marconi, D.; Meyer, M.; Niedziela, M.; Nowatschin, D.; Pantaleo, F.; Peiffer, T.; Perieanu, A.; Scharf, C.; Schleper, P.; Schmidt, A.; Schumann, S.; Schwandt, J.; Sonneveld, J.; Stadie, H.; Steinbrück, G.; Stober, F. M.; Stöver, M.; Tholen, H.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Vormwald, B.; Akbiyik, M.; Barth, C.; Baur, S.; Butz, E.; Caspart, R.; Chwalek, T.; Colombo, F.; De Boer, W.; Dierlamm, A.; Freund, B.; Friese, R.; Giffels, M.; Gilbert, A.; Haitz, D.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Kassel, F.; Kudella, S.; Mildner, H.; Mozer, M. U.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Schröder, M.; Shvetsov, I.; Sieber, G.; Simonis, H. J.; Ulrich, R.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Topsis-Giotis, I.; Karathanasis, G.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Evangelou, I.; Foudas, C.; Kokkas, P.; Mallios, S.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Strologas, J.; Triantis, F. A.; Csanad, M.; Filipovic, N.; Pasztor, G.; Bencze, G.; Hajdu, C.; Horvath, D.; Hunyadi, Á.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Makovec, A.; Molnar, J.; Szillasi, Z.; Bartók, M.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Choudhury, S.; Komaragiri, J. R.; Bahinipati, S.; Bhowmik, S.; Mal, P.; Mandal, K.; Nayak, A.; Sahoo, D. K.; Sahoo, N.; Swain, S. K.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Chawla, R.; Dhingra, N.; Kalsi, A. K.; Kaur, A.; Kaur, M.; Kumar, R.; Kumari, P.; Mehta, A.; Singh, J. B.; Walia, G.; Kumar, Ashok; Shah, Aashaq; Bhardwaj, A.; Chauhan, S.; Choudhary, B. C.; Garg, R. B.; Keshri, S.; Kumar, A.; Malhotra, S.; Naimuddin, M.; Ranjan, K.; Sharma, R.; Sharma, V.; Bhardwaj, R.; Bhattacharya, R.; Bhattacharya, S.; Bhawandeep, U.; Dey, S.; Dutt, S.; Dutta, S.; Ghosh, S.; Majumdar, N.; Modak, A.; Mondal, K.; Mukhopadhyay, S.; Nandan, S.; Purohit, A.; Roy, A.; Roy, D.; Roy Chowdhury, S.; Sarkar, S.; Sharan, M.; Thakur, S.; Behera, P. K.; Chudasama, R.; Dutta, D.; Jha, V.; Kumar, V.; Mohanty, A. K.; Netrakanti, P. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Dugad, S.; Mahakud, B.; Mitra, S.; Mohanty, G. B.; Sur, N.; Sutar, B.; Banerjee, S.; Bhattacharya, S.; Chatterjee, S.; Das, P.; Guchait, M.; Jain, Sa.; Kumar, S.; Maity, M.; Majumder, G.; Mazumdar, K.; Sarkar, T.; Wickramage, N.; Chauhan, S.; Dube, S.; Hegde, V.; Kapoor, A.; Kothekar, K.; Pandey, S.; Rane, A.; Sharma, S.; Chenarani, S.; Eskandari Tadavani, E.; Etesami, S. M.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Calabria, C.; Caputo, C.; Colaleo, A.; Creanza, D.; Cristella, L.; De Filippis, N.; De Palma, M.; Errico, F.; Fiore, L.; Iaselli, G.; Lezki, S.; Maggi, G.; Maggi, M.; Miniello, G.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Ranieri, A.; Selvaggi, G.; Sharma, A.; Silvestris, L.; Venditti, R.; Verwilligen, P.; Abbiendi, G.; Battilana, C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Chhibra, S. S.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Rossi, A. M.; Rovelli, T.; Siroli, G. P.; Tosi, N.; Albergo, S.; Costa, S.; Di Mattia, A.; Giordano, F.; Potenza, R.; Tricomi, A.; Tuve, C.; Barbagli, G.; Chatterjee, K.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Lenzi, P.; Meschini, M.; Paoletti, S.; Russo, L.; Sguazzoni, G.; Strom, D.; Viliani, L.; Benussi, L.; Bianco, S.; Fabbri, F.; Piccolo, D.; Primavera, F.; Biggio, C.; Calvelli, V.; Ferro, F.; Robutti, E.; Tosi, S.; Brianza, L.; Brivio, F.; Ciriolo, V.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Ghezzi, A.; Govoni, P.; Malberti, M.; Malvezzi, S.; Manzoni, R. A.; Menasce, D.; Moroni, L.; Paganoni, M.; Pauwels, K.; Pedrini, D.; Pigazzini, S.; Ragazzi, S.; Tabarelli de Fatis, T.; Buontempo, S.; Cavallo, N.; Di Guida, S.; Fabozzi, F.; Fienga, F.; Iorio, A. O. M.; Khan, W. A.; Lista, L.; Meola, S.; Paolucci, P.; Sciacca, C.; Thyssen, F.; Azzi, P.; Bacchetta, N.; Benato, L.; Bisello, D.; Boletti, A.; Carlin, R.; Carvalho Antunes De Oliveira, A.; Checchia, P.; De Castro Manzano, P.; Dorigo, T.; Gasparini, F.; Gasparini, U.; Gozzelino, A.; Lacaprara, S.; Lujan, P.; Margoni, M.; Meneguzzo, A. T.; Pozzobon, N.; Ronchese, P.; Rossin, R.; Simonetto, F.; Torassa, E.; Zanetti, M.; Zotto, P.; Zumerle, G.; Braghieri, A.; Fallavollita, F.; Magnani, A.; Montagna, P.; Ratti, S. P.; Re, V.; Ressegotti, M.; Riccardi, C.; Salvini, P.; Vai, I.; Vitulo, P.; Alunni Solestizi, L.; Biasini, M.; Bilei, G. M.; Cecchi, C.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Leonardi, R.; Manoni, E.; Mantovani, G.; Mariani, V.; Menichelli, M.; Rossi, A.; Santocchia, A.; Spiga, D.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Borrello, L.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Fedi, G.; Giannini, L.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Manca, E.; Mandorli, G.; Martini, L.; Messineo, A.; Palla, F.; Rizzi, A.; Savoy-Navarro, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Barone, L.; Cavallari, F.; Cipriani, M.; Daci, N.; Del Re, D.; Diemoz, M.; Gelli, S.; Longo, E.; Margaroli, F.; Marzocchi, B.; Meridiani, P.; Organtini, G.; Paramatti, R.; Preiato, F.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bartosik, N.; Bellan, R.; Biino, C.; Cartiglia, N.; Cenna, F.; Costa, M.; Covarelli, R.; Degano, A.; Demaria, N.; Kiani, B.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Monteil, E.; Monteno, M.; Obertino, M. M.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Ravera, F.; Romero, A.; Ruspa, M.; Sacchi, R.; Shchelina, K.; Sola, V.; Solano, A.; Staiano, A.; Traczyk, P.; Belforte, S.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Zanetti, A.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Lee, J.; Lee, S.; Lee, S. W.; Moon, C. S.; Oh, Y. D.; Sekmen, S.; Son, D. C.; Yang, Y. C.; Lee, A.; Kim, H.; Moon, D. H.; Oh, G.; Brochero Cifuentes, J. A.; Goh, J.; Kim, T. J.; Cho, S.; Choi, S.; Go, Y.; Gyun, D.; Ha, S.; Hong, B.; Jo, Y.; Kim, Y.; Lee, K.; Lee, K. S.; Lee, S.; Lim, J.; Park, S. K.; Roh, Y.; Almond, J.; Kim, J.; Kim, J. S.; Lee, H.; Lee, K.; Nam, K.; Oh, S. B.; Radburn-Smith, B. C.; Seo, S. h.; Yang, U. K.; Yoo, H. D.; Yu, G. B.; Choi, M.; Kim, H.; Kim, J. H.; Lee, J. S. H.; Park, I. C.; Ryu, G.; Choi, Y.; Hwang, C.; Lee, J.; Yu, I.; Dudenas, V.; Juodagalvis, A.; Vaitkus, J.; Ahmed, I.; Ibrahim, Z. A.; Md Ali, M. A. B.; Mohamad Idris, F.; Wan Abdullah, W. A. T.; Yusli, M. N.; Zolkapli, Z.; Reyes-Almanza, R.; Ramirez-Sanchez, G.; Duran-Osuna, M. C.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-De La Cruz, I.; Rabadan-Trejo, R. I.; Lopez-Fernandez, R.; Mejia Guisao, J.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Oropeza Barrera, C.; Vazquez Valencia, F.; Pedraza, I.; Salazar Ibarguen, H. A.; Uribe Estrada, C.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Saddique, A.; Shah, M. A.; Shoaib, M.; Waqas, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Zalewski, P.; Bunkowski, K.; Byszuk, A.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Pyskir, A.; Walczak, M.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Calpas, B.; Di Francesco, A.; Faccioli, P.; Gallinaro, M.; Hollar, J.; Leonardo, N.; Lloret Iglesias, L.; Nemallapudi, M. V.; Seixas, J.; Toldaiev, O.; Vadruccio, D.; Varela, J.; Afanasiev, S.; Bunin, P.; Gavrilenko, M.; Golutvin, I.; Gorbunov, I.; Kamenev, A.; Karjavin, V.; Lanev, A.; Malakhov, A.; Matveev, V.; Palichik, V.; Perelygin, V.; Shmatov, S.; Shulha, S.; Skatchkov, N.; Smirnov, V.; Voytishin, N.; Zarubin, A.; Ivanov, Y.; Kim, V.; Kuznetsova, E.; Levchenko, P.; Murzin, V.; Oreshkin, V.; Smirnov, I.; Sulimov, V.; Uvarov, L.; Vavilov, S.; Vorobyev, A.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Karneyeu, A.; Kirsanov, M.; Krasnikov, N.; Pashenkov, A.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Pozdnyakov, I.; Safronov, G.; Spiridonov, A.; Stepennov, A.; Toms, M.; Vlasov, E.; Zhokin, A.; Aushev, T.; Bylinkin, A.; Chistov, R.; Danilov, M.; Parygin, P.; Philippov, D.; Polikarpov, S.; Tarkovskii, E.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Terkulov, A.; Baskakov, A.; Belyaev, A.; Boos, E.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Klyukhin, V.; Kodolova, O.; Lokhtin, I.; Miagkov, I.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Snigirev, A.; Blinov, V.; Skovpen, Y.; Shtol, D.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Elumakhov, D.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Krychkine, V.; Petrov, V.; Ryutin, R.; Sobol, A.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Cirkovic, P.; Devetak, D.; Dordevic, M.; Milosevic, J.; Rekovic, V.; Alcaraz Maestre, J.; Barrio Luna, M.; Cerrada, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Escalante Del Valle, A.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Flix, J.; Fouz, M. C.; Garcia-Abia, P.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Pérez-Calero Yzquierdo, A.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Soares, M. S.; Álvarez Fernández, A.; de Trocóniz, J. F.; Missiroli, M.; Moran, D.; Cuevas, J.; Erice, C.; Fernandez Menendez, J.; Gonzalez Caballero, I.; González Fernández, J. R.; Palencia Cortezon, E.; Sanchez Cruz, S.; Suárez Andrés, I.; Vischia, P.; Vizan Garcia, J. M.; Cabrillo, I. J.; Calderon, A.; Chazin Quero, B.; Curras, E.; Duarte Campderros, J.; Fernandez, M.; Garcia-Ferrero, J.; Gomez, G.; Lopez Virto, A.; Marco, J.; Martinez Rivero, C.; Martinez Ruiz del Arbol, P.; Matorras, F.; Piedra Gomez, J.; Rodrigo, T.; Ruiz-Jimeno, A.; Scodellaro, L.; Trevisani, N.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Auffray, E.; Baillon, P.; Ball, A. H.; Barney, D.; Bianco, M.; Bloch, P.; Bocci, A.; Botta, C.; Camporesi, T.; Castello, R.; Cepeda, M.; Cerminara, G.; Chapon, E.; Chen, Y.; d'Enterria, D.; Dabrowski, A.; Daponte, V.; David, A.; De Gruttola, M.; De Roeck, A.; Di Marco, E.; Dobson, M.; Dorney, B.; du Pree, T.; Dünser, M.; Dupont, N.; Elliott-Peisert, A.; Everaerts, P.; Franzoni, G.; Fulcher, J.; Funk, W.; Gigi, D.; Gill, K.; Glege, F.; Gulhan, D.; Gundacker, S.; Guthoff, M.; Harris, P.; Hegeman, J.; Innocente, V.; Janot, P.; Karacheban, O.; Kieseler, J.; Kirschenmann, H.; Knünz, V.; Kornmayer, A.; Kortelainen, M. J.; Krammer, M.; Lange, C.; Lecoq, P.; Lourenço, C.; Lucchini, M. T.; Malgeri, L.; Mannelli, M.; Martelli, A.; Meijers, F.; Merlin, J. A.; Mersi, S.; Meschi, E.; Milenovic, P.; Moortgat, F.; Mulders, M.; Neugebauer, H.; Orfanelli, S.; Orsini, L.; Pape, L.; Perez, E.; Peruzzi, M.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Racz, A.; Reis, T.; Rolandi, G.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Seidel, M.; Selvaggi, M.; Sharma, A.; Silva, P.; Sphicas, P.; Stakia, A.; Steggemann, J.; Stoye, M.; Tosi, M.; Treille, D.; Triossi, A.; Tsirou, A.; Veckalns, V.; Veres, G. I.; Verweij, M.; Wardle, N.; Zeuner, W. D.; Bertl, W.; Caminada, L.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Rohe, T.; Wiederkehr, S. A.; Bachmair, F.; Bäni, L.; Berger, P.; Bianchini, L.; Casal, B.; Dissertori, G.; Dittmar, M.; Donegà, M.; Grab, C.; Heidegger, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Klijnsma, T.; Lustermann, W.; Mangano, B.; Marionneau, M.; Meinhard, M. T.; Meister, D.; Micheli, F.; Musella, P.; Nessi-Tedaldi, F.; Pandolfi, F.; Pata, J.; Pauss, F.; Perrin, G.; Perrozzi, L.; Quittnat, M.; Reichmann, M.; Schönenberger, M.; Shchutska, L.; Tavolaro, V. R.; Theofilatos, K.; Vesterbacka Olsson, M. L.; Wallny, R.; Zhu, D. H.; Aarrestad, T. K.; Amsler, C.; Canelli, M. F.; De Cosa, A.; Del Burgo, R.; Donato, S.; Galloni, C.; Hreus, T.; Kilminster, B.; Ngadiuba, J.; Pinna, D.; Rauco, G.; Robmann, P.; Salerno, D.; Seitz, C.; Takahashi, Y.; Zucchetta, A.; Candelise, V.; Doan, T. H.; Jain, Sh.; Khurana, R.; Kuo, C. M.; Lin, W.; Pozdnyakov, A.; Yu, S. S.; Kumar, Arun; Chang, P.; Chao, Y.; Chen, K. F.; Chen, P. H.; Fiori, F.; Hou, W.-S.; Hsiung, Y.; Liu, Y. F.; Lu, R.-S.; Paganis, E.; Psallidas, A.; Steen, A.; Tsai, J. f.; Asavapibhop, B.; Kovitanggoon, K.; Singh, G.; Srimanobhas, N.; Adiguzel, A.; Boran, F.; Cerci, S.; Damarseckin, S.; Demiroglu, Z. S.; Dozen, C.; Dumanoglu, I.; Girgis, S.; Gokbulut, G.; Guler, Y.; Hos, I.; Kangal, E. E.; Kara, O.; Kayis Topaksu, A.; Kiminsu, U.; Oglakci, M.; Onengut, G.; Ozdemir, K.; Sunar Cerci, D.; Tali, B.; Turkcapar, S.; Zorbakir, I. S.; Zorbilmez, C.; Bilin, B.; Karapinar, G.; Ocalan, K.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Kaya, M.; Kaya, O.; Tekten, S.; Yetkin, E. A.; Agaras, M. N.; Atay, S.; Cakir, A.; Cankocak, K.; Grynyov, B.; Levchuk, L.; Sorokin, P.; Aggleton, R.; Ball, F.; Beck, L.; Brooke, J. J.; Burns, D.; Clement, E.; Cussans, D.; Davignon, O.; Flacher, H.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Jacob, J.; Kreczko, L.; Lucas, C.; Newbold, D. M.; Paramesvaran, S.; Poll, A.; Sakuma, T.; Seif El Nasr-storey, S.; Smith, D.; Smith, V. J.; Bell, K. W.; Belyaev, A.; Brew, C.; Brown, R. M.; Calligaris, L.; Cieri, D.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Williams, T.; Auzinger, G.; Bainbridge, R.; Breeze, S.; Buchmuller, O.; Bundock, A.; Casasso, S.; Citron, M.; Colling, D.; Corpe, L.; Dauncey, P.; Davies, G.; De Wit, A.; Della Negra, M.; Di Maria, R.; Elwood, A.; Haddad, Y.; Hall, G.; Iles, G.; James, T.; Lane, R.; Laner, C.; Lyons, L.; Magnan, A.-M.; Malik, S.; Mastrolorenzo, L.; Matsushita, T.; Nash, J.; Nikitenko, A.; Palladino, V.; Pesaresi, M.; Raymond, D. M.; Richards, A.; Rose, A.; Scott, E.; Seez, C.; Shtipliyski, A.; Summers, S.; Tapper, A.; Uchida, K.; Vazquez Acosta, M.; Virdee, T.; Winterbottom, D.; Wright, J.; Zenz, S. C.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Borzou, A.; Call, K.; Dittmann, J.; Hatakeyama, K.; Liu, H.; Pastika, N.; Smith, C.; Bartek, R.; Dominguez, A.; Buccilli, A.; Cooper, S. I.; Henderson, C.; Rumerio, P.; West, C.; Arcaro, D.; Avetisyan, A.; Bose, T.; Gastler, D.; Rankin, D.; Richardson, C.; Rohlf, J.; Sulak, L.; Zou, D.; Benelli, G.; Cutts, D.; Garabedian, A.; Hakala, J.; Heintz, U.; Hogan, J. M.; Kwok, K. H. M.; Laird, E.; Landsberg, G.; Mao, Z.; Narain, M.; Pazzini, J.; Piperov, S.; Sagir, S.; Syarif, R.; Yu, D.; Band, R.; Brainerd, C.; Burns, D.; Calderon De La Barca Sanchez, M.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Flores, C.; Funk, G.; Gardner, M.; Ko, W.; Lander, R.; Mclean, C.; Mulhearn, M.; Pellett, D.; Pilot, J.; Shalhout, S.; Shi, M.; Smith, J.; Squires, M.; Stolp, D.; Tos, K.; Tripathi, M.; Wang, Z.; Bachtis, M.; Bravo, C.; Cousins, R.; Dasgupta, A.; Florent, A.; Hauser, J.; Ignatenko, M.; Mccoll, N.; Saltzberg, D.; Schnaible, C.; Valuev, V.; Bouvier, E.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Ghiasi Shirazi, S. M. A.; Hanson, G.; Heilman, J.; Jandir, P.; Kennedy, E.; Lacroix, F.; Long, O. R.; Olmedo Negrete, M.; Paneva, M. I.; Shrinivas, A.; Si, W.; Wang, L.; Wei, H.; Wimpenny, S.; Yates, B. R.; Branson, J. G.; Cittolin, S.; Derdzinski, M.; Gerosa, R.; Hashemi, B.; Holzner, A.; Klein, D.; Kole, G.; Krutelyov, V.; Letts, J.; Macneill, I.; Masciovecchio, M.; Olivito, D.; Padhi, S.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Tadel, M.; Vartak, A.; Wasserbaech, S.; Wood, J.; Würthwein, F.; Yagil, A.; Zevi Della Porta, G.; Amin, N.; Bhandari, R.; Bradmiller-Feld, J.; Campagnari, C.; Dishaw, A.; Dutta, V.; Franco Sevilla, M.; George, C.; Golf, F.; Gouskos, L.; Gran, J.; Heller, R.; Incandela, J.; Mullin, S. D.; Ovcharova, A.; Qu, H.; Richman, J.; Stuart, D.; Suarez, I.; Yoo, J.; Anderson, D.; Bendavid, J.; Bornheim, A.; Lawhorn, J. M.; Newman, H. B.; Nguyen, T.; Pena, C.; Spiropulu, M.; Vlimant, J. R.; Xie, S.; Zhang, Z.; Zhu, R. Y.; Andrews, M. B.; Ferguson, T.; Mudholkar, T.; Paulini, M.; Russ, J.; Sun, M.; Vogel, H.; Vorobiev, I.; Weinberg, M.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Leontsinis, S.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; Mcdermott, K.; Mirman, N.; Patterson, J. R.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Soffi, L.; Tan, S. M.; Tao, Z.; Thom, J.; Tucker, J.; Wittich, P.; Zientek, M.; Abdullin, S.; Albrow, M.; Apollinari, G.; Apresyan, A.; Apyan, A.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Canepa, A.; Cerati, G. B.; Cheung, H. W. K.; Chlebana, F.; Cremonesi, M.; Duarte, J.; Elvira, V. D.; Freeman, J.; Gecse, Z.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Lammel, S.; Lincoln, D.; Lipton, R.; Liu, M.; Liu, T.; Lopes De Sá, R.; Lykken, J.; Maeshima, K.; Magini, N.; Marraffino, J. M.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Ristori, L.; Schneider, B.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strait, J.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Field, R. D.; Furic, I. K.; Konigsberg, J.; Korytov, A.; Kotov, K.; Ma, P.; Matchev, K.; Mei, H.; Mitselmakher, G.; Rank, D.; Sperka, D.; Terentyev, N.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Joshi, Y. R.; Linn, S.; Markowitz, P.; Rodriguez, J. L.; Ackert, A.; Adams, T.; Askew, A.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Kolberg, T.; Martinez, G.; Perry, T.; Prosper, H.; Saha, A.; Santra, A.; Yohay, R.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Cavanaugh, R.; Chen, X.; Evdokimov, O.; Gerber, C. E.; Hangal, D. A.; Hofman, D. J.; Jung, K.; Kamin, J.; Sandoval Gonzalez, I. D.; Tonjes, M. B.; Trauger, H.; Varelas, N.; Wang, H.; Wu, Z.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; You, C.; Al-bataineh, A.; Baringer, P.; Bean, A.; Boren, S.; Bowen, J.; Castle, J.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Royon, C.; Sanders, S.; Schmitz, E.; Stringer, R.; Tapia Takaki, J. D.; Wang, Q.; Ivanov, A.; Kaadze, K.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Hadley, N. J.; Jabeen, S.; Jeng, G. Y.; Kellogg, R. G.; Kunkle, J.; Mignerey, A. C.; Ricci-Tam, F.; Shin, Y. H.; Skuja, A.; Tonwar, S. C.; Abercrombie, D.; Allen, B.; Azzolini, V.; Barbieri, R.; Baty, A.; Bi, R.; Brandt, S.; Busza, W.; Cali, I. A.; D'Alfonso, M.; Demiragli, Z.; Gomez Ceballos, G.; Goncharov, M.; Hsu, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Maier, B.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Tatar, K.; Velicanu, D.; Wang, J.; Wang, T. W.; Wyslouch, B.; Benvenuti, A. C.; Chatterjee, R. M.; Evans, A.; Hansen, P.; Kalafut, S.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Gonzalez Suarez, R.; Kamalieddin, R.; Kravchenko, I.; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Alyari, M.; Dolen, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Teixeira De Lima, R.; Trocino, D.; Wood, D.; Bhattacharya, S.; Charaf, O.; Hahn, K. A.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Hurtado Anampa, K.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Loukas, N.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Smith, G.; Taroni, S.; Wayne, M.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Ji, W.; Liu, B.; Luo, W.; Puigh, D.; Winer, B. L.; Wulsin, H. W.; Benaglia, A.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Higginbotham, S.; Lange, D.; Luo, J.; Marlow, D.; Mei, K.; Ojalvo, I.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Tully, C.; Malik, S.; Norberg, S.; Barker, A.; Barnes, V. E.; Das, S.; Folgueras, S.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Khatiwada, A.; Miller, D. H.; Neumeister, N.; Peng, C. C.; Schulte, J. F.; Sun, J.; Wang, F.; Xie, W.; Cheng, T.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y. t.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Ciesielski, R.; Goulianos, K.; Mesropian, C.; Agapitos, A.; Chou, J. P.; Christos, M.; Feigelis, K.; Gershtein, Y.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Montalvo, R.; Nash, K.; Osherson, M.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Zhou, B.; Delannoy, A. G.; Foerster, M.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Kamon, T.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Damgov, J.; De Guio, F.; Dudero, P. R.; Faulkner, J.; Gurpinar, E.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Peltola, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Hirosky, R.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Xia, F.; Harr, R.; Karchin, P. E.; Sturdy, J.; Zaleski, S.; Brodski, M.; Buchanan, J.; Caillol, C.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Hussain, U.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Pierro, G. A.; Polese, G.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.; CMS Collaboration

2017-12-01

A search for a signal consistent with the type-III seesaw mechanism in events with three or more electrons or muons is presented. The data sample consists of proton-proton collisions at √{s }=13 TeV collected by the CMS experiment at the LHC in 2016 and corresponds to an integrated luminosity of 35.9 fb-1 . Selection criteria based on the number of leptons and the invariant mass of oppositely charged lepton pairs are used to distinguish the signal from the standard model background. The observations are consistent with the expectations from standard model processes. The results are used to place limits on the production of heavy fermions of the type-III seesaw model as a function of the branching ratio to each lepton flavor. In the scenario of equal branching fractions to each lepton flavor, heavy fermions with masses below 840 GeV are excluded. This is the most sensitive probe to date of the type-III seesaw mechanism.
Protein structure validation and refinement using amide proton chemical shifts derived from quantum mechanics

DEFF Research Database (Denmark)

Christensen, Anders Steen; Linnet, Troels Emtekær; Borg, Mikael

2013-01-01

We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts - sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mechanical (QM) calculations and reproduces high level...
Proton pump inhibitor medication is associated with colonisation of gut flora in the oropharynx.

Science.gov (United States)

Tranberg, A; Thorarinsdottir, H R; Holmberg, A; Schött, U; Klarin, B

2018-03-08

The normal body exists in mutualistic balance with a large range of microbiota. The primary goal of this study was to establish whether there is an imbalance in the oropharyngeal flora early after hospital or ICU admittance, and whether flora differs between control, ward and critically ill patients. The secondary goal was to explore whether there are patient characteristics that can be associated with a disturbed oropharyngeal flora. Oropharyngeal cultures were obtained from three different study groups: (1) controls from the community, (2) ward patients and (3) critically ill patients, the two latter within 24 h after admittance. Cultures were obtained from 487 individuals: 77 controls, 193 ward patients and 217 critically ill patients. Abnormal pharyngeal flora was more frequent in critically ill and ward patients compared with controls (62.2% and 10.4% vs. 1.3%, P flora in the oropharynx was more frequent in critically ill patients compared with ward patients or controls (26.3% vs. 4.7% and 1.3%, P flora in the oropharynx in both ward and critically ill patients (P = 0.030 and P = 0.044, respectively). This study indicates that abnormal oropharyngeal flora is an early and frequent event in hospitalised patients and more so in the critically ill, compared to controls. Proton pump inhibitor medication is associated with colonisation of gut flora in the oropharynx. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Molecular cloning and sequence of cDNA encoding the plasma membrane proton pump (H+-ATPase) of Arabidopsis thaliana

International Nuclear Information System (INIS)

Harper, J.F.; Surowy, T.K.; Sussman, M.R.

1989-01-01

In plants, the transport of solutes across the plasma membrane is driven by a proton pump (H + -ATPase) that produces an electric potential and pH gradient. The authors isolated and sequenced a full-length cDNA clone that encodes this enzyme in Arabidopsis thaliana. The protein predicted from its nucleotide sequence encodes 959 amino acids and has a molecular mass of 104,207 Da. The plant protein shows structural features common to a family of cation-translocating ATPases found in the plasma membrane of prokaryotic and eukaryotic cells, with the greatest overall identity in amino acid sequence (36%) to the H + -ATPase observed in the plasma membrane of fungi. The structure predicted from a hydropathy plant contains at least eight transmembrane segments, with most of the protein (73%) extending into the cytoplasm and only 5% of the residues exposed on the external surface. Unique features of the plant enzyme include diverged sequences at the amino and carboxyl termini as well as greater hydrophilic character in three extracellular loops
The thermal and mechanical deformation study of up-stream pumping mechanical seal

International Nuclear Information System (INIS)

Chen, H L; Xu, C; Zuo, M Z; Wu, Q B

2015-01-01

Taking the viscosity-temperature relationship of the fluid film into consideration, a 3-D numerical model was established by ANSYS software which can simulate the heat transfer between the upstream pumping mechanical seal stationary and rotational rings and the fluid film between them as well as simulate the thermal deformation, structure deformation and the coupling deformation of them. According to the calculation result, thermal deformation causes the seal face expansion and the maximum thermal deformation appears at the inside of the seal ring. Pressure results in a mechanical deformation, the maximum deformation occurs at the top of the spiral groove and the overall trend is inward the mating face, opposite to the thermal deformation. The coupling deformation indicate that the thermal deformation can be partly counteracted by pressure deformation. Using this model, the relationship between deformation and shaft speed and the sealing liquid pressure was studied. It's found that the shaft speed will both enhance the thermal and structure deformation and the fluid pressure will enhance the structure deformation but has little to do with the thermal deformation. By changing the sealing material, it's found that material with low thermal expansion coefficient and low elastic modulus will suffer less thermal-pressure deformation
The thermal and mechanical deformation study of up-stream pumping mechanical seal

Science.gov (United States)

Chen, H. L.; Xu, C.; Zuo, M. Z.; Wu, Q. B.

2015-01-01

Taking the viscosity-temperature relationship of the fluid film into consideration, a 3-D numerical model was established by ANSYS software which can simulate the heat transfer between the upstream pumping mechanical seal stationary and rotational rings and the fluid film between them as well as simulate the thermal deformation, structure deformation and the coupling deformation of them. According to the calculation result, thermal deformation causes the seal face expansion and the maximum thermal deformation appears at the inside of the seal ring. Pressure results in a mechanical deformation, the maximum deformation occurs at the top of the spiral groove and the overall trend is inward the mating face, opposite to the thermal deformation. The coupling deformation indicate that the thermal deformation can be partly counteracted by pressure deformation. Using this model, the relationship between deformation and shaft speed and the sealing liquid pressure was studied. It's found that the shaft speed will both enhance the thermal and structure deformation and the fluid pressure will enhance the structure deformation but has little to do with the thermal deformation. By changing the sealing material, it's found that material with low thermal expansion coefficient and low elastic modulus will suffer less thermal-pressure deformation.
Exchangers man the pumps

Science.gov (United States)

Barkla, Bronwyn J; Hirschi, Kendal D

2008-01-01

Tonoplast-localised proton-coupled Ca2+ transporters encoded by cation/H+ exchanger (CAX) genes play a critical role in sequestering Ca2+ into the vacuole. These transporters may function in coordination with Ca2+ release channels, to shape stimulus-induced cytosolic Ca2+ elevations. Recent analysis of Arabidopsis CAX knockout mutants, particularly cax1 and cax3, identified a variety of phenotypes including sensitivity to abiotic stresses, which indicated that these transporters might play a role in mediating the plant's stress response. A common feature of these mutants was the perturbation of H+-ATPase activity at both the tonoplast and the plasma membrane, suggesting a tight interplay between the Ca2+/H+ exchangers and H+ pumps. We speculate that indirect regulation of proton flux by the exchangers may be as important as the direct regulation of Ca2+ flux. These results suggest cautious interpretation of mutant Ca2+/H+ exchanger phenotypes that may be due to either perturbed Ca2+ or H+ transport. PMID:19841670
Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy.

Science.gov (United States)

Kawara, Fumiaki; Fujita, Tsuyoshi; Morita, Yoshinori; Uda, Atsushi; Masuda, Atsuhiro; Saito, Masaya; Ooi, Makoto; Ishida, Tsukasa; Kondo, Yasuyuki; Yoshida, Shiei; Okuno, Tatsuya; Yano, Yoshihiko; Yoshida, Masaru; Kutsumi, Hiromu; Hayakumo, Takanobu; Yamashita, Kazuhiko; Hirano, Takeshi; Hirai, Midori; Azuma, Takeshi

2017-03-21

To elucidate the factors associated with residual gastroesophageal reflux disease (GERD) symptoms in patients receiving proton pump inhibitor (PPI) maintenance therapy in clinical practice. The study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed. The FSSG scores ranged from 1 to 28 points (median score: 7.5 points), and 19 patients (48.7%) had a score of 8 points or more. The patients' GSRS scores were significantly correlated with their FSSG scores (correlation coefficient = 0.47, P reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P reflux disease patients were significantly lower than those of the other patients (total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01). Approximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.
Use of proton pump inhibitors for the provision of stress ulcer prophylaxis: clinical and economic consequences.

Science.gov (United States)

Barletta, Jeffrey F; Sclar, David A

2014-01-01

The provision of stress ulcer prophylaxis (SUP) for the prevention of clinically significant bleeding is widely recognized as a crucial component of care in critically ill patients. Nevertheless, SUP is often provided to non-critically ill patients despite a risk for clinically significant bleeding of roughly 0.1 %. The overuse of SUP therefore introduces added risks for adverse drug events and cost, with minimal expected benefit in clinical outcome. Historically, histamine-2-receptor antagonists (H2RAs) have been the preferred agent for SUP; however, recent data have revealed proton pump inhibitors (PPIs) as the most common modality (76 %). There are no high quality randomized controlled trials demonstrating superiority with PPIs compared with H2RAs for the prevention of clinically significant bleeding associated with stress ulcers. In contrast, PPIs have recently been linked to several adverse effects including Clostridium difficile diarrhea and pneumonia. These complications have substantial economic consequences and have a marked impact on the overall cost effectiveness of PPI therapy. Nevertheless, PPI use remains widespread in patients who are at both high and low risk for clinically significant bleeding. This article will describe the utilization of PPIs for SUP and present the clinical and economic consequences linked to their use/overuse.
Quantum mechanics and hidden variables: A test of Bell's inequality by the measurement of the spin correlation in low-energy proton-proton scattering

International Nuclear Information System (INIS)

Lamehi-Rachti, M.; Mittig, W.

1976-01-01

The inequality of Bell has been tested by the measurement of the spin correlation in proton-proton scattering. Measurements were made at E/sub p/ = 13.2 and 13.7 MeV using carbon analyzers of 18.6 and 29 mg/cm 2 , respectively, accumulating a total of 10 4 coincidences. The experimental analyzing power, geometric correlation coefficients, and energy spectra are compared to the result of a Monte Carlo simulation of the apparatus. The results are in good agreement with quantum mechanics and in disagreement with the inequality of Bell if the same additional assumptions are made. The conditions for comparing the results of the experiments to the inequality of Bell are discussed
Structure and Mechanism of Proton Transport Through the Transmembrane Tetrameric M2 Protein Bundle of the Influenza A Virus

Energy Technology Data Exchange (ETDEWEB)

R Acharya; V Carnevale; G Fiorin; B Levine; A Polishchuk; V Balannick; I Samish; R Lamb; L Pinto; et al.

2011-12-31

The M2 proton channel from influenza A virus is an essential protein that mediates transport of protons across the viral envelope. This protein has a single transmembrane helix, which tetramerizes into the active channel. At the heart of the conduction mechanism is the exchange of protons between the His37 imidazole moieties of M2 and waters confined to the M2 bundle interior. Protons are conducted as the total charge of the four His37 side chains passes through 2{sup +} and 3{sup +} with a pK{sub a} near 6. A 1.65 {angstrom} resolution X-ray structure of the transmembrane protein (residues 25-46), crystallized at pH 6.5, reveals a pore that is lined by alternating layers of sidechains and well-ordered water clusters, which offer a pathway for proton conduction. The His37 residues form a box-like structure, bounded on either side by water clusters with well-ordered oxygen atoms at close distance. The conformation of the protein, which is intermediate between structures previously solved at higher and lower pH, suggests a mechanism by which conformational changes might facilitate asymmetric diffusion through the channel in the presence of a proton gradient. Moreover, protons diffusing through the channel need not be localized to a single His37 imidazole, but instead may be delocalized over the entire His-box and associated water clusters. Thus, the new crystal structure provides a possible unification of the discrete site versus continuum conduction models.
Proton dynamics in oxides: insight into the mechanics of proton conduction from quasielastic neutron scattering.

Science.gov (United States)

Karlsson, Maths

2015-01-07

This article is concerned with the use of quasielastic neutron scattering as a technique for investigation of the dynamical properties of proton conducting oxides. Currently, the main interest in these materials comes from their promise as electrolytes in future electrochemical devices and particularly through their use as electrolytes in next-generation, intermediate-temperature, fuel cells. However, the realization of such devices depends critically on the development of new, more highly proton conducting oxides. Such a development depends on increasing the current understanding of proton conduction in oxides and for this purpose quasielastic neutron scattering is an important mean. The aim of this article is to introduce the non-specialist reader to the basic principles of quasielastic neutron scattering, its advantages and disadvantages, to summarize the work that has been done on proton conducting oxides using this technique, as well as to discuss future opportunities within this field of research.
Champagne Heat Pump

Science.gov (United States)

Jones, Jack A.

2004-01-01

The term champagne heat pump denotes a developmental heat pump that exploits a cycle of absorption and desorption of carbon dioxide in an alcohol or other organic liquid. Whereas most heat pumps in common use in the United States are energized by mechanical compression, the champagne heat pump is energized by heating. The concept of heat pumps based on other absorption cycles energized by heat has been understood for years, but some of these heat pumps are outlawed in many areas because of the potential hazards posed by leakage of working fluids. For example, in the case of the water/ammonia cycle, there are potential hazards of toxicity and flammability. The organic-liquid/carbon dioxide absorption/desorption cycle of the champagne heat pump is similar to the water/ammonia cycle, but carbon dioxide is nontoxic and environmentally benign, and one can choose an alcohol or other organic liquid that is also relatively nontoxic and environmentally benign. Two candidate nonalcohol organic liquids are isobutyl acetate and amyl acetate. Although alcohols and many other organic liquids are flammable, they present little or no flammability hazard in the champagne heat pump because only the nonflammable carbon dioxide component of the refrigerant mixture is circulated to the evaporator and condenser heat exchangers, which are the only components of the heat pump in direct contact with air in habitable spaces.
Fast breeder reactor electromagnetic pump

International Nuclear Information System (INIS)

Araseki, Hideo; Murakami, Takahiro

2008-01-01

Main pumps circulating sodium in the FBR type reactor have been mechanical types, not electromagnetic pumps. Electromagnetic pump of 1-2 m 3 /min has been used as an auxiliary pump. Large sized electromagnetic pumps such as several hundred m 3 /min have not been commercialized due to technical difficulties with electromagnetic instability and pressure pulsations. This article explained electromagnetic and fluid equations and magnetic Reynolds number related with electromagnetic pumps and numerical analysis of instability characteristics and pressure pulsations and then described applications of the results to FBR system. Magnetic Reynolds number must be chosen less than one with appropriate operating frequency and optimum slip of 0.2-0.4. (T. Tanaka)
Analogies between respiration and a light-driven proton pump as sources of energy for active glutamate transport in Halobacterium halobium

Science.gov (United States)

Belliveau, J. W.; Lanyi, J. K.

1977-01-01

Halobacterium halobium is known to contain sheets of bacteriorhodopsin, a pigment which upon exposure to light undergoes cyclic protonation and deprotonation, resulting in net H(+) translocation. In this paper, experiments were conducted to test H. halobium cell envelope vesicles for respiration-induced glutamate uptake. It is shown that glutamate transport in H. halobium cell envelope vesicles can occur as a result of respiration, as well as light acting on bacteriorhodopsin. Glutamate transport can be energized by the oxidation of dimethyl phenylenediamine, and the properties of the transport system are entirely analogous to those observed with illumination as the source of energy. In the case of respiration-dependent glutamate transport, the transportation is also driven by a Na(+) gradient, thereby confirming the existence of a single glutamate transport system independent of the source of energy. The analogy observed is indirect evidence that the cytochrome oxidase of H. halobium functions as a H(+) pump.
Impact of mechanical- and maintenance-induced failures of main reactor coolant pump seals on plant safety

International Nuclear Information System (INIS)

Azarm, M.A.; Boccio, J.L.; Mitra, S.

1985-12-01

This document presents an investigation of the safety impact resulting from mechanical- and maintenance-induced reactor coolant pump (RCP) seal failures in nuclear power plants. A data survey of the pump seal failures for existing nuclear power plants in the US from several available sources was performed. The annual frequency of pump seal failures in a nuclear power plant was estimated based on the concept of hazard rate and dependency evaluation. The conditional probability of various sizes of leak rates given seal failures was then evaluated. The safety impact of RCP seal failures, in terms of contribution to plant core-melt frequency, was also evaluated for three nuclear power plants. For leak rates below the normal makeup capacity and the impact of plant safety were discussed qualitatively, whereas for leak rates beyond the normal make up capacity, formal PRA methodologies were applied. 22 refs., 17 figs., 19 tabs
Outcomes in patients with nonerosive reflux disease treated with a proton pump inhibitor and alginic acid ± glycyrrhetinic acid and anthocyanosides

Directory of Open Access Journals (Sweden)

Di Pierro F

2013-03-01

Full Text Available Francesco Di Pierro,1 Mario Gatti,2 Giuliana Rapacioli,3 Leandro Ivaldi4 1Velleja Research, Milan, 2Gastroenterology Department, Giussano Hospital, Monza-Brianza, 3AIOR, Piacenza, 4Digestive Endoscopic Department, Ceva Hospital, Ceva, Cuneo, Italy Background: The purpose of this study was to compare the efficacy of alginic acid alone versus alginic acid combined with low doses of pure glycyrrhetinic acid and bilberry anthocyanosides as an addon to conventional proton pump inhibitor therapy in relieving symptoms associated with nonerosive reflux disease. Methods: This prospective, randomized, 8-week, open-label trial was conducted at two centers. Sixty-three patients with persistent symptoms of gastroesophageal reflux disease and normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A (n = 31 were treated with pantoprazole and a formula (Mirgeal® containing alginic acid and low doses of pure glycyrrhetinic acid + standardized Vaccinium myrtillus extract for 4 weeks, then crossed over to the multi-ingredient formula for a further 4 weeks. Patients in group B (n = 32 were treated pantoprazole and alginic acid alone twice daily, then crossed over to alginic acid twice daily for a further 4 weeks. Efficacy was assessed by medical evaluation of a symptom relief score, estimated using a visual analog scale (0–10. Side effects, tolerability, and compliance were also assessed. Results: Of the 63 patients enrolled in the study, 58 (29 in group A and 29 in group B completed the 8-week trial. The baseline characteristics were comparable between the two groups. During the study, significant differences were recorded in symptom scores for both groups. In group A, symptoms of chest pain, heartburn, and abdominal swelling were less serious than in group B. Treatment A was better tolerated, did not induce hypertension, and had fewer side effects than treatment B. No significant differences in compliance were found between the
Proton therapy physics

CERN Document Server

2012-01-01

Proton Therapy Physics goes beyond current books on proton therapy to provide an in-depth overview of the physics aspects of this radiation therapy modality, eliminating the need to dig through information scattered in the medical physics literature. After tracing the history of proton therapy, the book summarizes the atomic and nuclear physics background necessary for understanding proton interactions with tissue. It describes the physics of proton accelerators, the parameters of clinical proton beams, and the mechanisms to generate a conformal dose distribution in a patient. The text then covers detector systems and measuring techniques for reference dosimetry, outlines basic quality assurance and commissioning guidelines, and gives examples of Monte Carlo simulations in proton therapy. The book moves on to discussions of treatment planning for single- and multiple-field uniform doses, dose calculation concepts and algorithms, and precision and uncertainties for nonmoving and moving targets. It also exami...
Thermomechanical piston pump development

Science.gov (United States)

Sabelman, E. E.

1971-01-01

A thermally powered reciprocating pump has been devised to replace or augment an electric pump for the transport of temperature-control fluid on the Thermoelectric Outer Planet Spacecraft (TOPS). The thermally powered pump operates cyclically by extracting heat energy from the fluid by means of a vapor-pressure expansion system and by using the heat to perform the mechanical work of pumping. A feasibility test unit has been constructed to provide an output of 7 cu in during a 10- to 100-second cycle. It operates with a fluid input temperature of 200 to 300 F and a heat sink temperature of 0 to 30 F.
Research on Cavitation Regions of Upstream Pumping Mechanical Seal Based on Dynamic Mesh Technique

Directory of Open Access Journals (Sweden)

Huilong Chen

2014-08-01

Full Text Available In order to study the cavitation area of the Upstream Pumping Mechanical Seal, three-dimensional microgap inner flow field of the Upstream Pumping Mechanical Seal was simulated with multiphase flow cavitation model and dynamic mesh technique based on hydrodynamic lubrication theory. Furthermore, the simulated result was compared with the experimental data. The results show that the simulated result with the Zwart-Gerber-Belamri cavitation model was much closer to the experimental data. The area of cavitation inception mainly occurred at the concave side of the spiral groove and surrounding region without spiral grooves, which was nearly covered by the inner diameter to roots of grooves; in addition, the region near the surface of the stationary ring was primary cavitation location. The area of cavitation has little relationship with the medium pressure; however, it became larger following increasing rotating speed in the range of researched operating conditions. Moreover the boundary of cavitated area was transformed from smooth to rough, which occurred in similar film thickness. When cavitation number was decreasing, which was conducive to improving the lubrication performance of sealed auxiliary, it made the sealing stability decline.

Theoretical thermodynamic analysis of Rankine power cycle with thermal driven pump

International Nuclear Information System (INIS)

Lakew, Amlaku Abie; Bolland, Olav; Ladam, Yves

2011-01-01

Highlights: → The work is focused on theoretical aspects of thermal driven pump (TDP) Rankine cycle. → The mechanical pump is replaced by thermal driven pump. → Important parameters of thermal driven pump Rankine cycle are investigated. → TDP Rankine cycle produce more power but it requires additional low grade heat. - Abstract: A new approach to improve the performance of supercritical carbon dioxide Rankine cycle which uses low temperature heat source is presented. The mechanical pump in conventional supercritical carbon dioxide Rankine cycle is replaced by thermal driven pump. The concept of thermal driven pump is to increase the pressure of a fluid in a closed container by supplying heat. A low grade heat source is used to increase the pressure of the fluid instead of a mechanical pump, this increase the net power output and avoid the need for mechanical pump which requires regular maintenance and operational cost. The thermal driven pump considered is a shell and tube heat exchanger where the working fluid is contained in the tube, a tube diameter of 5 mm is chosen to reduce the heating time. The net power output of the Rankine cycle with thermal driven pump is compared to that of Rankine cycle with mechanical pump and it is observed that the net power output is higher when low grade thermal energy is used to pressurize the working fluid. The thermal driven pump consumes additional heat at low temperature (60 o C) to pressurize the working fluid.
Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population.

Directory of Open Access Journals (Sweden)

Nigam H Shah

Full Text Available Proton pump inhibitors (PPIs have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.Using a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population.In multiple data sources, we found gastroesophageal reflux disease (GERD patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09-1.24 with myocardial infarction (MI. Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07-3.78; P = 0.031 increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.Consistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.
40 CFR 63.1026 - Pumps in light liquid service standards.

Science.gov (United States)

2010-07-01

... this section. (A) Each dual mechanical seal system is operated with the barrier fluid at a pressure... monomers; (ii) 2,000 parts per million or greater for pumps in food/medical service; and (iii) 1,000 parts...—(1) Dual mechanical seal pumps. Each pump equipped with a dual mechanical seal system that includes a...
The pathway for serial proton supply to the active site of nitrogenase: enhanced density functional modeling of the Grotthuss mechanism.

Science.gov (United States)

Dance, Ian

2015-11-07

Nitrogenase contains a well defined and conserved chain of water molecules leading to the FeMo cofactor (FeMo-co, an [Fe7MoCS9] cluster with bidentate chelation of Mo by homocitrate) that is the active site where N2 and other substrates are sequentially hydrogenated using multiple protons and electrons. The function of this chain is proposed to be a proton wire, serially translocating protons to triply-bridging S3B of FeMo-co, where, concomitant with electron transfer to FeMo-co, an H atom is generated on S3B. Density functional simulations of this proton translocation mechanism are reported here, using a large 269-atom model that includes all residues hydrogen bonded to and surrounding the water chain, and likely to influence proton transfer: three carboxylate O atoms of obligatory homocitrate are essential. The mechanism involves the standard two components of the Grotthuss mechanism, namely H atom slides that shift H3O(+) from one water site to the next, and HOH molecular rotations that convert backward (posterior) OH bonds in the water chain to forward (anterior) OH bonds. The topography of the potential energy surface for each of these steps has been mapped. H atom slides pass through very short (ca. 2.5 Å) O-H-O hydrogen bonds, while HOH rotations involve the breaking of O-HO hydrogen bonds, and the occurrence of long (up to 3.6 Å) separations between contiguous water molecules. Both steps involve low potential energy barriers, chain, occurring as ripples. These characteristics of the 'Grotthuss two-step', coupled with a buffering ability of two carboxylate O atoms of homocitrate, and combined with density functional characterisation of the final proton slide from the ultimate water molecule to S3B (including electron addition), have been choreographed into a complete mechanism for serial hydrogenation of FeMo-co. The largest potential barrier is estimated to be 14 kcal mol(-1). These results are discussed in the context of reactivity data for nitrogenase
Parametric Model for Astrophysical Proton-Proton Interactions and Applications

Energy Technology Data Exchange (ETDEWEB)

Karlsson, Niklas [KTH Royal Institute of Technology, Stockholm (Sweden)

2007-01-01

Observations of gamma-rays have been made from celestial sources such as active galaxies, gamma-ray bursts and supernova remnants as well as the Galactic ridge. The study of gamma rays can provide information about production mechanisms and cosmic-ray acceleration. In the high-energy regime, one of the dominant mechanisms for gamma-ray production is the decay of neutral pions produced in interactions of ultra-relativistic cosmic-ray nuclei and interstellar matter. Presented here is a parametric model for calculations of inclusive cross sections and transverse momentum distributions for secondary particles--gamma rays, e^±, v_e, $\\bar{v}$_e, v_μ and $\\bar{μ}$_e--produced in proton-proton interactions. This parametric model is derived on the proton-proton interaction model proposed by Kamae et al.; it includes the diffraction dissociation process, Feynman-scaling violation and the logarithmically rising inelastic proton-proton cross section. To improve fidelity to experimental data for lower energies, two baryon resonance excitation processes were added; one representing the Δ(1232) and the other multiple resonances with masses around 1600 MeV/c². The model predicts the power-law spectral index for all secondary particle to be about 0.05 lower in absolute value than that of the incident proton and their inclusive cross sections to be larger than those predicted by previous models based on the Feynman-scaling hypothesis. The applications of the presented model in astrophysics are plentiful. It has been implemented into the Galprop code to calculate the contribution due to pion decays in the Galactic plane. The model has also been used to estimate the cosmic-ray flux in the Large Magellanic Cloud based on HI, CO and gamma-ray observations. The transverse momentum distributions enable calculations when the proton distribution is anisotropic. It is shown that the gamma-ray spectrum and flux due to a
Supercritical waste oxidation pump investigation

International Nuclear Information System (INIS)

Thurston, G.; Garcia, K.

1993-02-01

This report investigates the pumping techniques and pumping equipment that would be appropriate for a 5,000 gallon per day supercritical water oxidation waste disposal facility. The pumps must boost water, waste, and additives from atmospheric pressure to approximately 27.6 MPa (4,000 psia). The required flow ranges from 10 gpm to less than 0.1 gpm. For the higher flows, many commercial piston pumps are available. These pumps have packing and check-valves that will require periodic maintenance; probably at 2 to 6 month intervals. Several commercial diaphragm pumps were also discovered that could pump the higher flow rates. Diaphragm pumps have the advantage of not requiring dynamic seals. For the lower flows associated with the waste and additive materials, commercial diaphragm pumps. are available. Difficult to pump materials that are sticky, radioactive, or contain solids, could be injected with an accumulator using an inert gas as the driving mechanism. The information presented in this report serves as a spring board for trade studies and the development of equipment specifications
pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity.

Science.gov (United States)

De Milito, Angelo; Canese, Rossella; Marino, Maria Lucia; Borghi, Martina; Iero, Manuela; Villa, Antonello; Venturi, Giulietta; Lozupone, Francesco; Iessi, Elisabetta; Logozzi, Mariantonia; Della Mina, Pamela; Santinami, Mario; Rodolfo, Monica; Podo, Franca; Rivoltini, Licia; Fais, Stefano

2010-07-01

Metastatic melanoma is associated with poor prognosis and still limited therapeutic options. An innovative treatment approach for this disease is represented by targeting acidosis, a feature characterizing tumor microenvironment and playing an important role in cancer malignancy. Proton pump inhibitors (PPI), such as esomeprazole (ESOM) are prodrugs functionally activated by acidic environment, fostering pH neutralization by inhibiting proton extrusion. We used human melanoma cell lines and xeno-transplated SCID mice to provide preclinical evidence of ESOM antineoplastic activity. Human melanoma cell lines, characterized by different mutation and signaling profiles, were treated with ESOM in different pH conditions and evaluated for proliferation, viability and cell death. SCID mice engrafted with human melanoma were used to study ESOM administration effects on tumor growth and tumor pH by magnetic resonance spectroscopy (MRS). ESOM inhibited proliferation of melanoma cells in vitro and induced a cytotoxicity strongly boosted by low pH culture conditions. ESOM-induced tumor cell death occurred via rapid intracellular acidification and activation of several caspases. Inhibition of caspases activity by pan-caspase inhibitor z-vad-fmk completely abrogated the ESOM-induced cell death. ESOM administration (2.5 mg kg(-1)) to SCID mice engrafted with human melanoma reduced tumor growth, consistent with decrease of proliferating cells and clear reduction of pH gradients in tumor tissue. Moreover, systemic ESOM administration dramatically increased survival of human melanoma-bearing animals, in absence of any relevant toxicity. These data show preclinical evidence supporting the use of PPI as novel therapeutic strategy for melanoma, providing the proof of concept that PPI target human melanoma modifying tumor pH gradients.
Cytochrome cbb3 of Thioalkalivibrio is a Na+-pumping cytochrome oxidase

NARCIS (Netherlands)

Muntyan, M.S.; Cherepanov, D.A.; Malinen, A.M.; Bloch, D.A.; Sorokin, D.Y.; Severina, I.I.; Ivashina, T.V.; Lahti, R.; Muyzer, G.; Skulachev, V.P.

2015-01-01

Cytochrome c oxidases (Coxs) are the basic energy transducers in the respiratory chain of the majority of aerobic organisms. Coxs studied to date are redox-driven proton-pumping enzymes belonging to one of three subfamilies: A-, B-, and C-type oxidases. The C-type oxidases (cbb3 cytochromes), which
Coherent evolution of parahydrogen induced polarisation using laser pump, NMR probe spectroscopy: Theoretical framework and experimental observation.

Science.gov (United States)

Halse, Meghan E; Procacci, Barbara; Henshaw, Sarah-Louise; Perutz, Robin N; Duckett, Simon B

2017-05-01

We recently reported a pump-probe method that uses a single laser pulse to introduce parahydrogen (p-H 2 ) into a metal dihydride complex and then follows the time-evolution of the p-H 2 -derived nuclear spin states by NMR. We present here a theoretical framework to describe the oscillatory behaviour of the resultant hyperpolarised NMR signals using a product operator formalism. We consider the cases where the p-H 2 -derived protons form part of an AX, AXY, AXYZ or AA'XX' spin system in the product molecule. We use this framework to predict the patterns for 2D pump-probe NMR spectra, where the indirect dimension represents the evolution during the pump-probe delay and the positions of the cross-peaks depend on the difference in chemical shift of the p-H 2 -derived protons and the difference in their couplings to other nuclei. The evolution of the NMR signals of the p-H 2 -derived protons, as well as the transfer of hyperpolarisation to other NMR-active nuclei in the product, is described. The theoretical framework is tested experimentally for a set of ruthenium dihydride complexes representing the different spin systems. Theoretical predictions and experimental results agree to within experimental error for all features of the hyperpolarised 1 H and 31 P pump-probe NMR spectra. Thus we establish the laser pump, NMR probe approach as a robust way to directly observe and quantitatively analyse the coherent evolution of p-H 2 -derived spin order over micro-to-millisecond timescales. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Feasibility study on the type of KALIMER coolant circulation pump

International Nuclear Information System (INIS)

Nam, H. Y.; Kim, Y. K.; Lee, Y. B.; Hwang, J. S.; Choi, S. K.

1997-07-01

The characteristics of mechanical pump and electromagnetic (EM) pump for liquid sodium coolant in a liquid metal reactor are compared and analysed as a design concept of KALIMER coolant pumps. The type of coolant circulation pump affects the selection of reactor type, economics, and reliability of reactor. Though the mechanical pump has much application experience and give satisfaction to the reliability of developed reactor type, the possibility of development is limited and its large weight and volume have a negative effect on the design of the economical liquid metal reactor. The large scale electromagnetic pump has not been verified yet, but it is expected to be demonstrated in time. Because the size of EM pump is small relative to the mechanical pump, the compact reactor design is possible. Therefore the selection of EM pump can be one of the methods to improve the economics. Since the shape of EM pump can be varied according to the arrangement of electromagnet coils, a new or unique reactor type can be developed easily in the process of KALIMER development. In the view point of economic LMR development, it is desirable to adopt the electromagnetic pump. (author). 50 refs., 11 tabs., 24 figs
Search for Evidence of the Type-III Seesaw Mechanism in Multilepton Final States in Proton-Proton Collisions at sqrt[s]=13 TeV.

Science.gov (United States)

Sirunyan, A M; Tumasyan, A; Adam, W; Ambrogi, F; Asilar, E; Bergauer, T; Brandstetter, J; Brondolin, E; Dragicevic, M; Erö, J; Flechl, M; Friedl, M; Frühwirth, R; Ghete, V M; Grossmann, J; Hrubec, J; Jeitler, M; König, A; Krammer, N; Krätschmer, I; Liko, D; Madlener, T; Mikulec, I; Pree, E; Rabady, D; Rad, N; Rohringer, H; Schieck, J; Schöfbeck, R; Spanring, M; Spitzbart, D; Waltenberger, W; Wittmann, J; Wulz, C-E; Zarucki, M; Chekhovsky, V; Mossolov, V; Suarez Gonzalez, J; De Wolf, E A; Di Croce, D; Janssen, X; Lauwers, J; Van Haevermaet, H; Van Mechelen, P; Van Remortel, N; Abu Zeid, S; Blekman, F; D'Hondt, J; De Bruyn, I; De Clercq, J; Deroover, K; Flouris, G; Lontkovskyi, D; Lowette, S; Moortgat, S; Moreels, L; Python, Q; Skovpen, K; Tavernier, S; Van Doninck, W; Van Mulders, P; Van Parijs, I; Brun, H; Clerbaux, B; De Lentdecker, G; Delannoy, H; Fasanella, G; Favart, L; Goldouzian, R; Grebenyuk, A; Karapostoli, G; Lenzi, T; Luetic, J; Maerschalk, T; Marinov, A; Randle-Conde, A; Seva, T; Vander Velde, C; Vanlaer, P; Vannerom, D; Yonamine, R; Zenoni, F; Zhang, F; Cimmino, A; Cornelis, T; Dobur, D; Fagot, A; Gul, M; Khvastunov, I; Poyraz, D; Roskas, C; Salva, S; Tytgat, M; Verbeke, W; Zaganidis, N; Bakhshiansohi, H; Bondu, O; Brochet, S; Bruno, G; Caudron, A; De Visscher, S; Delaere, C; Delcourt, M; Francois, B; Giammanco, A; Jafari, A; Komm, M; Krintiras, G; Lemaitre, V; Magitteri, A; Mertens, A; Musich, M; Piotrzkowski, K; Quertenmont, L; Vidal Marono, M; Wertz, S; Beliy, N; Aldá Júnior, W L; Alves, F L; Alves, G A; Brito, L; Correa Martins Junior, M; Hensel, C; Moraes, A; Pol, M E; Rebello Teles, P; Belchior Batista Das Chagas, E; Carvalho, W; Chinellato, J; Custódio, A; Da Costa, E M; Da Silveira, G G; De Jesus Damiao, D; Fonseca De Souza, S; Huertas Guativa, L M; Malbouisson, H; Melo De Almeida, M; Mora Herrera, C; Mundim, L; Nogima, H; Santoro, A; Sznajder, A; Tonelli Manganote, E J; Torres Da Silva De Araujo, F; Vilela Pereira, A; Ahuja, S; Bernardes, C A; Tomei, T R Fernandez Perez; Gregores, E M; Mercadante, P G; Novaes, S F; Padula, Sandra S; Romero Abad, D; Ruiz Vargas, J C; Aleksandrov, A; Hadjiiska, R; Iaydjiev, P; Misheva, M; Rodozov, M; Shopova, M; Stoykova, S; Sultanov, G; Dimitrov, A; Glushkov, I; Litov, L; Pavlov, B; Petkov, P; Fang, W; Gao, X; Ahmad, M; Bian, J G; Chen, G M; Chen, H S; Chen, M; Chen, Y; Jiang, C H; Leggat, D; Liao, H; Liu, Z; Romeo, F; Shaheen, S M; Spiezia, A; Tao, J; Wang, C; Wang, Z; Yazgan, E; Zhang, H; Zhao, J; Ban, Y; Chen, G; Li, Q; Liu, S; Mao, Y; Qian, S J; Wang, D; Xu, Z; Avila, C; Cabrera, A; Chaparro Sierra, L F; Florez, C; González Hernández, C F; Ruiz Alvarez, J D; Courbon, B; Godinovic, N; Lelas, D; Puljak, I; Ribeiro Cipriano, P M; Sculac, T; Antunovic, Z; Kovac, M; Brigljevic, V; Ferencek, D; Kadija, K; Mesic, B; Starodumov, A; Susa, T; Ather, M W; Attikis, A; Mavromanolakis, G; Mousa, J; Nicolaou, C; Ptochos, F; Razis, P A; Rykaczewski, H; Finger, M; Finger, M; Carrera Jarrin, E; El-Khateeb, E; Elgammal, S; Ellithi Kamel, A; Dewanjee, R K; Kadastik, M; Perrini, L; Raidal, M; Tiko, A; Veelken, C; Eerola, P; Pekkanen, J; Voutilainen, M; Härkönen, J; Järvinen, T; Karimäki, V; Kinnunen, R; Lampén, T; Lassila-Perini, K; Lehti, S; Lindén, T; Luukka, P; Tuominen, E; Tuominiemi, J; Tuovinen, E; Talvitie, J; Tuuva, T; Besancon, M; Couderc, F; Dejardin, M; Denegri, D; Faure, J L; Ferri, F; Ganjour, S; Ghosh, S; Givernaud, A; Gras, P; Hamel de Monchenault, G; Jarry, P; Kucher, I; Locci, E; Machet, M; Malcles, J; Negro, G; Rander, J; Rosowsky, A; Sahin, M Ö; Titov, M; Abdulsalam, A; Antropov, I; Baffioni, S; Beaudette, F; Busson, P; Cadamuro, L; Charlot, C; Granier de Cassagnac, R; Jo, M; Lisniak, S; Lobanov, A; Martin Blanco, J; Nguyen, M; Ochando, C; Ortona, G; Paganini, P; Pigard, P; Regnard, S; Salerno, R; Sauvan, J B; Sirois, Y; Stahl Leiton, A G; Strebler, T; Yilmaz, Y; Zabi, A; Zghiche, A; Agram, J-L; Andrea, J; Bloch, D; Brom, J-M; Buttignol, M; Chabert, E C; Chanon, N; Collard, C; Conte, E; Coubez, X; Fontaine, J-C; Gelé, D; Goerlach, U; Jansová, M; Le Bihan, A-C; Tonon, N; Van Hove, P; Gadrat, S; Beauceron, S; Bernet, C; Boudoul, G; Chierici, R; Contardo, D; Depasse, P; El Mamouni, H; Fay, J; Finco, L; Gascon, S; Gouzevitch, M; Grenier, G; Ille, B; Lagarde, F; Laktineh, I B; Lethuillier, M; Mirabito, L; Pequegnot, A L; Perries, S; Popov, A; Sordini, V; Vander Donckt, M; Viret, S; Toriashvili, T; Lomidze, D; Autermann, C; Beranek, S; Feld, L; Kiesel, M K; Klein, K; Lipinski, M; Preuten, M; Schomakers, C; Schulz, J; Verlage, T; Albert, A; Dietz-Laursonn, E; Duchardt, D; Endres, M; Erdmann, M; Erdweg, S; Esch, T; Fischer, R; Güth, A; Hamer, M; Hebbeker, T; Heidemann, C; Hoepfner, K; Knutzen, S; Merschmeyer, M; Meyer, A; Millet, P; Mukherjee, S; Olschewski, M; Padeken, K; Pook, T; Radziej, M; Reithler, H; Rieger, M; Scheuch, F; Teyssier, D; Thüer, S; Flügge, G; Kargoll, B; Kress, T; Künsken, A; Lingemann, J; Müller, T; Nehrkorn, A; Nowack, A; Pistone, C; Pooth, O; Stahl, A; Aldaya Martin, M; Arndt, T; Asawatangtrakuldee, C; Beernaert, K; Behnke, O; Behrens, U; Bermúdez Martínez, A; Bin Anuar, A A; Borras, K; Botta, V; Campbell, A; Connor, P; Contreras-Campana, C; Costanza, F; Diez Pardos, C; Eckerlin, G; Eckstein, D; Eichhorn, T; Eren, E; Gallo, E; Garay Garcia, J; Geiser, A; Gizhko, A; Grados Luyando, J M; Grohsjean, A; Gunnellini, P; Harb, A; Hauk, J; Hempel, M; Jung, H; Kalogeropoulos, A; Kasemann, M; Keaveney, J; Kleinwort, C; Korol, I; Krücker, D; Lange, W; Lelek, A; Lenz, T; Leonard, J; Lipka, K; Lohmann, W; Mankel, R; Melzer-Pellmann, I-A; Meyer, A B; Mittag, G; Mnich, J; Mussgiller, A; Ntomari, E; Pitzl, D; Raspereza, A; Roland, B; Savitskyi, M; Saxena, P; Shevchenko, R; Spannagel, S; Stefaniuk, N; Van Onsem, G P; Walsh, R; Wen, Y; Wichmann, K; Wissing, C; Zenaiev, O; Bein, S; Blobel, V; Centis Vignali, M; Dreyer, T; Garutti, E; Gonzalez, D; Haller, J; Hinzmann, A; Hoffmann, M; Karavdina, A; Klanner, R; Kogler, R; Kovalchuk, N; Kurz, S; Lapsien, T; Marchesini, I; Marconi, D; Meyer, M; Niedziela, M; Nowatschin, D; Pantaleo, F; Peiffer, T; Perieanu, A; Scharf, C; Schleper, P; Schmidt, A; Schumann, S; Schwandt, J; Sonneveld, J; Stadie, H; Steinbrück, G; Stober, F M; Stöver, M; Tholen, H; Troendle, D; Usai, E; Vanelderen, L; Vanhoefer, A; Vormwald, B; Akbiyik, M; Barth, C; Baur, S; Butz, E; Caspart, R; Chwalek, T; Colombo, F; De Boer, W; Dierlamm, A; Freund, B; Friese, R; Giffels, M; Gilbert, A; Haitz, D; Hartmann, F; Heindl, S M; Husemann, U; Kassel, F; Kudella, S; Mildner, H; Mozer, M U; Müller, Th; Plagge, M; Quast, G; Rabbertz, K; Schröder, M; Shvetsov, I; Sieber, G; Simonis, H J; Ulrich, R; Wayand, S; Weber, M; Weiler, T; Williamson, S; Wöhrmann, C; Wolf, R; Anagnostou, G; Daskalakis, G; Geralis, T; Giakoumopoulou, V A; Kyriakis, A; Loukas, D; Topsis-Giotis, I; Karathanasis, G; Kesisoglou, S; Panagiotou, A; Saoulidou, N; Evangelou, I; Foudas, C; Kokkas, P; Mallios, S; Manthos, N; Papadopoulos, I; Paradas, E; Strologas, J; Triantis, F A; Csanad, M; Filipovic, N; Pasztor, G; Bencze, G; Hajdu, C; Horvath, D; Hunyadi, Á; Sikler, F; Veszpremi, V; Vesztergombi, G; Zsigmond, A J; Beni, N; Czellar, S; Karancsi, J; Makovec, A; Molnar, J; Szillasi, Z; Bartók, M; Raics, P; Trocsanyi, Z L; Ujvari, B; Choudhury, S; Komaragiri, J R; Bahinipati, S; Bhowmik, S; Mal, P; Mandal, K; Nayak, A; Sahoo, D K; Sahoo, N; Swain, S K; Bansal, S; Beri, S B; Bhatnagar, V; Chawla, R; Dhingra, N; Kalsi, A K; Kaur, A; Kaur, M; Kumar, R; Kumari, P; Mehta, A; Singh, J B; Walia, G; Kumar, Ashok; Shah, Aashaq; Bhardwaj, A; Chauhan, S; Choudhary, B C; Garg, R B; Keshri, S; Kumar, A; Malhotra, S; Naimuddin, M; Ranjan, K; Sharma, R; Sharma, V; Bhardwaj, R; Bhattacharya, R; Bhattacharya, S; Bhawandeep, U; Dey, S; Dutt, S; Dutta, S; Ghosh, S; Majumdar, N; Modak, A; Mondal, K; Mukhopadhyay, S; Nandan, S; Purohit, A; Roy, A; Roy, D; Roy Chowdhury, S; Sarkar, S; Sharan, M; Thakur, S; Behera, P K; Chudasama, R; Dutta, D; Jha, V; Kumar, V; Mohanty, A K; Netrakanti, P K; Pant, L M; Shukla, P; Topkar, A; Aziz, T; Dugad, S; Mahakud, B; Mitra, S; Mohanty, G B; Sur, N; Sutar, B; Banerjee, S; Bhattacharya, S; Chatterjee, S; Das, P; Guchait, M; Jain, Sa; Kumar, S; Maity, M; Majumder, G; Mazumdar, K; Sarkar, T; Wickramage, N; Chauhan, S; Dube, S; Hegde, V; Kapoor, A; Kothekar, K; Pandey, S; Rane, A; Sharma, S; Chenarani, S; Eskandari Tadavani, E; Etesami, S M; Khakzad, M; Mohammadi Najafabadi, M; Naseri, M; Paktinat Mehdiabadi, S; Rezaei Hosseinabadi, F; Safarzadeh, B; Zeinali, M; Felcini, M; Grunewald, M; Abbrescia, M; Calabria, C; Caputo, C; Colaleo, A; Creanza, D; Cristella, L; De Filippis, N; De Palma, M; Errico, F; Fiore, L; Iaselli, G; Lezki, S; Maggi, G; Maggi, M; Miniello, G; My, S; Nuzzo, S; Pompili, A; Pugliese, G; Radogna, R; Ranieri, A; Selvaggi, G; Sharma, A; Silvestris, L; Venditti, R; Verwilligen, P; Abbiendi, G; Battilana, C; Bonacorsi, D; Braibant-Giacomelli, S; Campanini, R; Capiluppi, P; Castro, A; Cavallo, F R; Chhibra, S S; Codispoti, G; Cuffiani, M; Dallavalle, G M; Fabbri, F; Fanfani, A; Fasanella, D; Giacomelli, P; Grandi, C; Guiducci, L; Marcellini, S; Masetti, G; Montanari, A; Navarria, F L; Perrotta, A; Rossi, A M; Rovelli, T; Siroli, G P; Tosi, N; Albergo, S; Costa, S; Di Mattia, A; Giordano, F; Potenza, R; Tricomi, A; Tuve, C; Barbagli, G; Chatterjee, K; Ciulli, V; Civinini, C; D'Alessandro, R; Focardi, E; Lenzi, P; Meschini, M; Paoletti, S; Russo, L; Sguazzoni, G; Strom, D; Viliani, L; Benussi, L; Bianco, S; Fabbri, F; Piccolo, D; Primavera, F; Biggio, C; Calvelli, V; Ferro, F; Robutti, E; Tosi, S; Brianza, L; Brivio, F; Ciriolo, V; Dinardo, M E; Fiorendi, S; Gennai, S; Ghezzi, A; Govoni, P; Malberti, M; Malvezzi, S; Manzoni, R A; Menasce, D; Moroni, L; Paganoni, M; Pauwels, K; Pedrini, D; Pigazzini, S; Ragazzi, S; Tabarelli de Fatis, T; Buontempo, S; Cavallo, N; Di Guida, S; Fabozzi, F; Fienga, F; Iorio, A O M; Khan, W A; Lista, L; Meola, S; Paolucci, P; Sciacca, C; Thyssen, F; Azzi, P; Bacchetta, N; Benato, L; Bisello, D; Boletti, A; Carlin, R; Carvalho Antunes De Oliveira, A; Checchia, P; De Castro Manzano, P; Dorigo, T; Gasparini, F; Gasparini, U; Gozzelino, A; Lacaprara, S; Lujan, P; Margoni, M; Meneguzzo, A T; Pozzobon, N; Ronchese, P; Rossin, R; Simonetto, F; Torassa, E; Zanetti, M; Zotto, P; Zumerle, G; Braghieri, A; Fallavollita, F; Magnani, A; Montagna, P; Ratti, S P; Re, V; Ressegotti, M; Riccardi, C; Salvini, P; Vai, I; Vitulo, P; Alunni Solestizi, L; Biasini, M; Bilei, G M; Cecchi, C; Ciangottini, D; Fanò, L; Lariccia, P; Leonardi, R; Manoni, E; Mantovani, G; Mariani, V; Menichelli, M; Rossi, A; Santocchia, A; Spiga, D; Androsov, K; Azzurri, P; Bagliesi, G; Bernardini, J; Boccali, T; Borrello, L; Castaldi, R; Ciocci, M A; Dell'Orso, R; Fedi, G; Giannini, L; Giassi, A; Grippo, M T; Ligabue, F; Lomtadze, T; Manca, E; Mandorli, G; Martini, L; Messineo, A; Palla, F; Rizzi, A; Savoy-Navarro, A; Spagnolo, P; Tenchini, R; Tonelli, G; Venturi, A; Verdini, P G; Barone, L; Cavallari, F; Cipriani, M; Daci, N; Del Re, D; Diemoz, M; Gelli, S; Longo, E; Margaroli, F; Marzocchi, B; Meridiani, P; Organtini, G; Paramatti, R; Preiato, F; Rahatlou, S; Rovelli, C; Santanastasio, F; Amapane, N; Arcidiacono, R; Argiro, S; Arneodo, M; Bartosik, N; Bellan, R; Biino, C; Cartiglia, N; Cenna, F; Costa, M; Covarelli, R; Degano, A; Demaria, N; Kiani, B; Mariotti, C; Maselli, S; Migliore, E; Monaco, V; Monteil, E; Monteno, M; Obertino, M M; Pacher, L; Pastrone, N; Pelliccioni, M; Pinna Angioni, G L; Ravera, F; Romero, A; Ruspa, M; Sacchi, R; Shchelina, K; Sola, V; Solano, A; Staiano, A; Traczyk, P; Belforte, S; Casarsa, M; Cossutti, F; Della Ricca, G; Zanetti, A; Kim, D H; Kim, G N; Kim, M S; Lee, J; Lee, S; Lee, S W; Moon, C S; Oh, Y D; Sekmen, S; Son, D C; Yang, Y C; Lee, A; Kim, H; Moon, D H; Oh, G; Brochero Cifuentes, J A; Goh, J; Kim, T J; Cho, S; Choi, S; Go, Y; Gyun, D; Ha, S; Hong, B; Jo, Y; Kim, Y; Lee, K; Lee, K S; Lee, S; Lim, J; Park, S K; Roh, Y; Almond, J; Kim, J; Kim, J S; Lee, H; Lee, K; Nam, K; Oh, S B; Radburn-Smith, B C; Seo, S H; Yang, U K; Yoo, H D; Yu, G B; Choi, M; Kim, H; Kim, J H; Lee, J S H; Park, I C; Ryu, G; Choi, Y; Hwang, C; Lee, J; Yu, I; Dudenas, V; Juodagalvis, A; Vaitkus, J; Ahmed, I; Ibrahim, Z A; Md Ali, M A B; Mohamad Idris, F; Wan Abdullah, W A T; Yusli, M N; Zolkapli, Z; Reyes-Almanza, R; Ramirez-Sanchez, G; Duran-Osuna, M C; Castilla-Valdez, H; De La Cruz-Burelo, E; Heredia-De La Cruz, I; Rabadan-Trejo, R I; Lopez-Fernandez, R; Mejia Guisao, J; Sanchez-Hernandez, A; Carrillo Moreno, S; Oropeza Barrera, C; Vazquez Valencia, F; Pedraza, I; Salazar Ibarguen, H A; Uribe Estrada, C; Morelos Pineda, A; Krofcheck, D; Butler, P H; Ahmad, A; Ahmad, M; Hassan, Q; Hoorani, H R; Saddique, A; Shah, M A; Shoaib, M; Waqas, M; Bialkowska, H; Bluj, M; Boimska, B; Frueboes, T; Górski, M; Kazana, M; Nawrocki, K; Romanowska-Rybinska, K; Szleper, M; Zalewski, P; Bunkowski, K; Byszuk, A; Doroba, K; Kalinowski, A; Konecki, M; Krolikowski, J; Misiura, M; Olszewski, M; Pyskir, A; Walczak, M; Bargassa, P; Beirão Da Cruz E Silva, C; Calpas, B; Di Francesco, A; Faccioli, P; Gallinaro, M; Hollar, J; Leonardo, N; Lloret Iglesias, L; Nemallapudi, M V; Seixas, J; Toldaiev, O; Vadruccio, D; Varela, J; Afanasiev, S; Bunin, P; Gavrilenko, M; Golutvin, I; Gorbunov, I; Kamenev, A; Karjavin, V; Lanev, A; Malakhov, A; Matveev, V; Palichik, V; Perelygin, V; Shmatov, S; Shulha, S; Skatchkov, N; Smirnov, V; Voytishin, N; Zarubin, A; Ivanov, Y; Kim, V; Kuznetsova, E; Levchenko, P; Murzin, V; Oreshkin, V; Smirnov, I; Sulimov, V; Uvarov, L; Vavilov, S; Vorobyev, A; Andreev, Yu; Dermenev, A; Gninenko, S; Golubev, N; Karneyeu, A; Kirsanov, M; Krasnikov, N; Pashenkov, A; Tlisov, D; Toropin, A; Epshteyn, V; Gavrilov, V; Lychkovskaya, N; Popov, V; Pozdnyakov, I; Safronov, G; Spiridonov, A; Stepennov, A; Toms, M; Vlasov, E; Zhokin, A; Aushev, T; Bylinkin, A; Chistov, R; Danilov, M; Parygin, P; Philippov, D; Polikarpov, S; Tarkovskii, E; Andreev, V; Azarkin, M; Dremin, I; Kirakosyan, M; Terkulov, A; Baskakov, A; Belyaev, A; Boos, E; Dubinin, M; Dudko, L; Ershov, A; Gribushin, A; Klyukhin, V; Kodolova, O; Lokhtin, I; Miagkov, I; Obraztsov, S; Petrushanko, S; Savrin, V; Snigirev, A; Blinov, V; Skovpen, Y; Shtol, D; Azhgirey, I; Bayshev, I; Bitioukov, S; Elumakhov, D; Kachanov, V; Kalinin, A; Konstantinov, D; Krychkine, V; Petrov, V; Ryutin, R; Sobol, A; Troshin, S; Tyurin, N; Uzunian, A; Volkov, A; Adzic, P; Cirkovic, P; Devetak, D; Dordevic, M; Milosevic, J; Rekovic, V; Alcaraz Maestre, J; Barrio Luna, M; Cerrada, M; Colino, N; De La Cruz, B; Delgado Peris, A; Escalante Del Valle, A; Fernandez Bedoya, C; Fernández Ramos, J P; Flix, J; Fouz, M C; Garcia-Abia, P; Gonzalez Lopez, O; Goy Lopez, S; Hernandez, J M; Josa, M I; Pérez-Calero Yzquierdo, A; Puerta Pelayo, J; Quintario Olmeda, A; Redondo, I; Romero, L; Soares, M S; Álvarez Fernández, A; de Trocóniz, J F; Missiroli, M; Moran, D; Cuevas, J; Erice, C; Fernandez Menendez, J; Gonzalez Caballero, I; González Fernández, J R; Palencia Cortezon, E; Sanchez Cruz, S; Suárez Andrés, I; Vischia, P; Vizan Garcia, J M; Cabrillo, I J; Calderon, A; Chazin Quero, B; Curras, E; Duarte Campderros, J; Fernandez, M; Garcia-Ferrero, J; Gomez, G; Lopez Virto, A; Marco, J; Martinez Rivero, C; Martinez Ruiz Del Arbol, P; Matorras, F; Piedra Gomez, J; Rodrigo, T; Ruiz-Jimeno, A; Scodellaro, L; Trevisani, N; Vila, I; Vilar Cortabitarte, R; Abbaneo, D; Auffray, E; Baillon, P; Ball, A H; Barney, D; Bianco, M; Bloch, P; Bocci, A; Botta, C; Camporesi, T; Castello, R; Cepeda, M; Cerminara, G; Chapon, E; Chen, Y; d'Enterria, D; Dabrowski, A; Daponte, V; David, A; De Gruttola, M; De Roeck, A; Di Marco, E; Dobson, M; Dorney, B; du Pree, T; Dünser, M; Dupont, N; Elliott-Peisert, A; Everaerts, P; Franzoni, G; Fulcher, J; Funk, W; Gigi, D; Gill, K; Glege, F; Gulhan, D; Gundacker, S; Guthoff, M; Harris, P; Hegeman, J; Innocente, V; Janot, P; Karacheban, O; Kieseler, J; Kirschenmann, H; Knünz, V; Kornmayer, A; Kortelainen, M J; Krammer, M; Lange, C; Lecoq, P; Lourenço, C; Lucchini, M T; Malgeri, L; Mannelli, M; Martelli, A; Meijers, F; Merlin, J A; Mersi, S; Meschi, E; Milenovic, P; Moortgat, F; Mulders, M; Neugebauer, H; Orfanelli, S; Orsini, L; Pape, L; Perez, E; Peruzzi, M; Petrilli, A; Petrucciani, G; Pfeiffer, A; Pierini, M; Racz, A; Reis, T; Rolandi, G; Rovere, M; Sakulin, H; Schäfer, C; Schwick, C; Seidel, M; Selvaggi, M; Sharma, A; Silva, P; Sphicas, P; Stakia, A; Steggemann, J; Stoye, M; Tosi, M; Treille, D; Triossi, A; Tsirou, A; Veckalns, V; Veres, G I; Verweij, M; Wardle, N; Zeuner, W D; Bertl, W; Caminada, L; Deiters, K; Erdmann, W; Horisberger, R; Ingram, Q; Kaestli, H C; Kotlinski, D; Langenegger, U; Rohe, T; Wiederkehr, S A; Bachmair, F; Bäni, L; Berger, P; Bianchini, L; Casal, B; Dissertori, G; Dittmar, M; Donegà, M; Grab, C; Heidegger, C; Hits, D; Hoss, J; Kasieczka, G; Klijnsma, T; Lustermann, W; Mangano, B; Marionneau, M; Meinhard, M T; Meister, D; Micheli, F; Musella, P; Nessi-Tedaldi, F; Pandolfi, F; Pata, J; Pauss, F; Perrin, G; Perrozzi, L; Quittnat, M; Reichmann, M; Schönenberger, M; Shchutska, L; Tavolaro, V R; Theofilatos, K; Vesterbacka Olsson, M L; Wallny, R; Zhu, D H; Aarrestad, T K; Amsler, C; Canelli, M F; De Cosa, A; Del Burgo, R; Donato, S; Galloni, C; Hreus, T; Kilminster, B; Ngadiuba, J; Pinna, D; Rauco, G; Robmann, P; Salerno, D; Seitz, C; Takahashi, Y; Zucchetta, A; Candelise, V; Doan, T H; Jain, Sh; Khurana, R; Kuo, C M; Lin, W; Pozdnyakov, A; Yu, S S; Kumar, Arun; Chang, P; Chao, Y; Chen, K F; Chen, P H; Fiori, F; Hou, W-S; Hsiung, Y; Liu, Y F; Lu, R-S; Paganis, E; Psallidas, A; Steen, A; Tsai, J F; Asavapibhop, B; Kovitanggoon, K; Singh, G; Srimanobhas, N; Adiguzel, A; Boran, F; Cerci, S; Damarseckin, S; Demiroglu, Z S; Dozen, C; Dumanoglu, I; Girgis, S; Gokbulut, G; Guler, Y; Hos, I; Kangal, E E; Kara, O; Kayis Topaksu, A; Kiminsu, U; Oglakci, M; Onengut, G; Ozdemir, K; Sunar Cerci, D; Tali, B; Turkcapar, S; Zorbakir, I S; Zorbilmez, C; Bilin, B; Karapinar, G; Ocalan, K; Yalvac, M; Zeyrek, M; Gülmez, E; Kaya, M; Kaya, O; Tekten, S; Yetkin, E A; Agaras, M N; Atay, S; Cakir, A; Cankocak, K; Grynyov, B; Levchuk, L; Sorokin, P; Aggleton, R; Ball, F; Beck, L; Brooke, J J; Burns, D; Clement, E; Cussans, D; Davignon, O; Flacher, H; Goldstein, J; Grimes, M; Heath, G P; Heath, H F; Jacob, J; Kreczko, L; Lucas, C; Newbold, D M; Paramesvaran, S; Poll, A; Sakuma, T; Seif El Nasr-Storey, S; Smith, D; Smith, V J; Bell, K W; Belyaev, A; Brew, C; Brown, R M; Calligaris, L; Cieri, D; Cockerill, D J A; Coughlan, J A; Harder, K; Harper, S; Olaiya, E; Petyt, D; Shepherd-Themistocleous, C H; Thea, A; Tomalin, I R; Williams, T; Auzinger, G; Bainbridge, R; Breeze, S; Buchmuller, O; Bundock, A; Casasso, S; Citron, M; Colling, D; Corpe, L; Dauncey, P; Davies, G; De Wit, A; Della Negra, M; Di Maria, R; Elwood, A; Haddad, Y; Hall, G; Iles, G; James, T; Lane, R; Laner, C; Lyons, L; Magnan, A-M; Malik, S; Mastrolorenzo, L; Matsushita, T; Nash, J; Nikitenko, A; Palladino, V; Pesaresi, M; Raymond, D M; Richards, A; Rose, A; Scott, E; Seez, C; Shtipliyski, A; Summers, S; Tapper, A; Uchida, K; Vazquez Acosta, M; Virdee, T; Winterbottom, D; Wright, J; Zenz, S C; Cole, J E; Hobson, P R; Khan, A; Kyberd, P; Reid, I D; Symonds, P; Teodorescu, L; Turner, M; Borzou, A; Call, K; Dittmann, J; Hatakeyama, K; Liu, H; Pastika, N; Smith, C; Bartek, R; Dominguez, A; Buccilli, A; Cooper, S I; Henderson, C; Rumerio, P; West, C; Arcaro, D; Avetisyan, A; Bose, T; Gastler, D; Rankin, D; Richardson, C; Rohlf, J; Sulak, L; Zou, D; Benelli, G; Cutts, D; Garabedian, A; Hakala, J; Heintz, U; Hogan, J M; Kwok, K H M; Laird, E; Landsberg, G; Mao, Z; Narain, M; Pazzini, J; Piperov, S; Sagir, S; Syarif, R; Yu, D; Band, R; Brainerd, C; Burns, D; Calderon De La Barca Sanchez, M; Chertok, M; Conway, J; Conway, R; Cox, P T; Erbacher, R; Flores, C; Funk, G; Gardner, M; Ko, W; Lander, R; Mclean, C; Mulhearn, M; Pellett, D; Pilot, J; Shalhout, S; Shi, M; Smith, J; Squires, M; Stolp, D; Tos, K; Tripathi, M; Wang, Z; Bachtis, M; Bravo, C; Cousins, R; Dasgupta, A; Florent, A; Hauser, J; Ignatenko, M; Mccoll, N; Saltzberg, D; Schnaible, C; Valuev, V; Bouvier, E; Burt, K; Clare, R; Ellison, J; Gary, J W; Ghiasi Shirazi, S M A; Hanson, G; Heilman, J; Jandir, P; Kennedy, E; Lacroix, F; Long, O R; Olmedo Negrete, M; Paneva, M I; Shrinivas, A; Si, W; Wang, L; Wei, H; Wimpenny, S; Yates, B R; Branson, J G; Cittolin, S; Derdzinski, M; Gerosa, R; Hashemi, B; Holzner, A; Klein, D; Kole, G; Krutelyov, V; Letts, J; Macneill, I; Masciovecchio, M; Olivito, D; Padhi, S; Pieri, M; Sani, M; Sharma, V; Simon, S; Tadel, M; Vartak, A; Wasserbaech, S; Wood, J; Würthwein, F; Yagil, A; Zevi Della Porta, G; Amin, N; Bhandari, R; Bradmiller-Feld, J; Campagnari, C; Dishaw, A; Dutta, V; Franco Sevilla, M; George, C; Golf, F; Gouskos, L; Gran, J; Heller, R; Incandela, J; Mullin, S D; Ovcharova, A; Qu, H; Richman, J; Stuart, D; Suarez, I; Yoo, J; Anderson, D; Bendavid, J; Bornheim, A; Lawhorn, J M; Newman, H B; Nguyen, T; Pena, C; Spiropulu, M; Vlimant, J R; Xie, S; Zhang, Z; Zhu, R Y; Andrews, M B; Ferguson, T; Mudholkar, T; Paulini, M; Russ, J; Sun, M; Vogel, H; Vorobiev, I; Weinberg, M; Cumalat, J P; Ford, W T; Jensen, F; Johnson, A; Krohn, M; Leontsinis, S; Mulholland, T; Stenson, K; Wagner, S R; Alexander, J; Chaves, J; Chu, J; Dittmer, S; Mcdermott, K; Mirman, N; Patterson, J R; Rinkevicius, A; Ryd, A; Skinnari, L; Soffi, L; Tan, S M; Tao, Z; Thom, J; Tucker, J; Wittich, P; Zientek, M; Abdullin, S; Albrow, M; Apollinari, G; Apresyan, A; Apyan, A; Banerjee, S; Bauerdick, L A T; Beretvas, A; Berryhill, J; Bhat, P C; Bolla, G; Burkett, K; Butler, J N; Canepa, A; Cerati, G B; Cheung, H W K; Chlebana, F; Cremonesi, M; Duarte, J; Elvira, V D; Freeman, J; Gecse, Z; Gottschalk, E; Gray, L; Green, D; Grünendahl, S; Gutsche, O; Harris, R M; Hasegawa, S; Hirschauer, J; Hu, Z; Jayatilaka, B; Jindariani, S; Johnson, M; Joshi, U; Klima, B; Kreis, B; Lammel, S; Lincoln, D; Lipton, R; Liu, M; Liu, T; Lopes De Sá, R; Lykken, J; Maeshima, K; Magini, N; Marraffino, J M; Maruyama, S; Mason, D; McBride, P; Merkel, P; Mrenna, S; Nahn, S; O'Dell, V; Pedro, K; Prokofyev, O; Rakness, G; Ristori, L; Schneider, B; Sexton-Kennedy, E; Soha, A; Spalding, W J; Spiegel, L; Stoynev, S; Strait, J; Strobbe, N; Taylor, L; Tkaczyk, S; Tran, N V; Uplegger, L; Vaandering, E W; Vernieri, C; Verzocchi, M; Vidal, R; Wang, M; Weber, H A; Whitbeck, A; Acosta, D; Avery, P; Bortignon, P; Bourilkov, D; Brinkerhoff, A; Carnes, A; Carver, M; Curry, D; Field, R D; Furic, I K; Konigsberg, J; Korytov, A; Kotov, K; Ma, P; Matchev, K; Mei, H; Mitselmakher, G; Rank, D; Sperka, D; Terentyev, N; Thomas, L; Wang, J; Wang, S; Yelton, J; Joshi, Y R; Linn, S; Markowitz, P; Rodriguez, J L; Ackert, A; Adams, T; Askew, A; Hagopian, S; Hagopian, V; Johnson, K F; Kolberg, T; Martinez, G; Perry, T; Prosper, H; Saha, A; Santra, A; Yohay, R; Baarmand, M M; Bhopatkar, V; Colafranceschi, S; Hohlmann, M; Noonan, D; Roy, T; Yumiceva, F; Adams, M R; Apanasevich, L; Berry, D; Betts, R R; Cavanaugh, R; Chen, X; Evdokimov, O; Gerber, C E; Hangal, D A; Hofman, D J; Jung, K; Kamin, J; Sandoval Gonzalez, I D; Tonjes, M B; Trauger, H; Varelas, N; Wang, H; Wu, Z; Zhang, J; Bilki, B; Clarida, W; Dilsiz, K; Durgut, S; Gandrajula, R P; Haytmyradov, M; Khristenko, V; Merlo, J-P; Mermerkaya, H; Mestvirishvili, A; Moeller, A; Nachtman, J; Ogul, H; Onel, Y; Ozok, F; Penzo, A; Snyder, C; Tiras, E; Wetzel, J; Yi, K; Blumenfeld, B; Cocoros, A; Eminizer, N; Fehling, D; Feng, L; Gritsan, A V; Maksimovic, P; Roskes, J; Sarica, U; Swartz, M; Xiao, M; You, C; Al-Bataineh, A; Baringer, P; Bean, A; Boren, S; Bowen, J; Castle, J; Khalil, S; Kropivnitskaya, A; Majumder, D; Mcbrayer, W; Murray, M; Royon, C; Sanders, S; Schmitz, E; Stringer, R; Tapia Takaki, J D; Wang, Q; Ivanov, A; Kaadze, K; Maravin, Y; Mohammadi, A; Saini, L K; Skhirtladze, N; Toda, S; Rebassoo, F; Wright, D; Anelli, C; Baden, A; Baron, O; Belloni, A; Calvert, B; Eno, S C; Ferraioli, C; Hadley, N J; Jabeen, S; Jeng, G Y; Kellogg, R G; Kunkle, J; Mignerey, A C; Ricci-Tam, F; Shin, Y H; Skuja, A; Tonwar, S C; Abercrombie, D; Allen, B; Azzolini, V; Barbieri, R; Baty, A; Bi, R; Brandt, S; Busza, W; Cali, I A; D'Alfonso, M; Demiragli, Z; Gomez Ceballos, G; Goncharov, M; Hsu, D; Iiyama, Y; Innocenti, G M; Klute, M; Kovalskyi, D; Lai, Y S; Lee, Y-J; Levin, A; Luckey, P D; Maier, B; Marini, A C; Mcginn, C; Mironov, C; Narayanan, S; Niu, X; Paus, C; Roland, C; Roland, G; Salfeld-Nebgen, J; Stephans, G S F; Tatar, K; Velicanu, D; Wang, J; Wang, T W; Wyslouch, B; Benvenuti, A C; Chatterjee, R M; Evans, A; Hansen, P; Kalafut, S; Kubota, Y; Lesko, Z; Mans, J; Nourbakhsh, S; Ruckstuhl, N; Rusack, R; Turkewitz, J; Acosta, J G; Oliveros, S; Avdeeva, E; Bloom, K; Claes, D R; Fangmeier, C; Gonzalez Suarez, R; Kamalieddin, R; Kravchenko, I; Monroy, J; Siado, J E; Snow, G R; Stieger, B; Alyari, M; Dolen, J; Godshalk, A; Harrington, C; Iashvili, I; Nguyen, D; Parker, A; Rappoccio, S; Roozbahani, B; Alverson, G; Barberis, E; Hortiangtham, A; Massironi, A; Morse, D M; Nash, D; Orimoto, T; Teixeira De Lima, R; Trocino, D; Wood, D; Bhattacharya, S; Charaf, O; Hahn, K A; Mucia, N; Odell, N; Pollack, B; Schmitt, M H; Sung, K; Trovato, M; Velasco, M; Dev, N; Hildreth, M; Hurtado Anampa, K; Jessop, C; Karmgard, D J; Kellams, N; Lannon, K; Loukas, N; Marinelli, N; Meng, F; Mueller, C; Musienko, Y; Planer, M; Reinsvold, A; Ruchti, R; Smith, G; Taroni, S; Wayne, M; Wolf, M; Woodard, A; Alimena, J; Antonelli, L; Bylsma, B; Durkin, L S; Flowers, S; Francis, B; Hart, A; Hill, C; Ji, W; Liu, B; Luo, W; Puigh, D; Winer, B L; Wulsin, H W; Benaglia, A; Cooperstein, S; Driga, O; Elmer, P; Hardenbrook, J; Hebda, P; Higginbotham, S; Lange, D; Luo, J; Marlow, D; Mei, K; Ojalvo, I; Olsen, J; Palmer, C; Piroué, P; Stickland, D; Tully, C; Malik, S; Norberg, S; Barker, A; Barnes, V E; Das, S; Folgueras, S; Gutay, L; Jha, M K; Jones, M; Jung, A W; Khatiwada, A; Miller, D H; Neumeister, N; Peng, C C; Schulte, J F; Sun, J; Wang, F; Xie, W; Cheng, T; Parashar, N; Stupak, J; Adair, A; Akgun, B; Chen, Z; Ecklund, K M; Geurts, F J M; Guilbaud, M; Li, W; Michlin, B; Northup, M; Padley, B P; Roberts, J; Rorie, J; Tu, Z; Zabel, J; Bodek, A; de Barbaro, P; Demina, R; Duh, Y T; Ferbel, T; Galanti, M; Garcia-Bellido, A; Han, J; Hindrichs, O; Khukhunaishvili, A; Lo, K H; Tan, P; Verzetti, M; Ciesielski, R; Goulianos, K; Mesropian, C; Agapitos, A; Chou, J P; Christos, M; Feigelis, K; Gershtein, Y; Gómez Espinosa, T A; Halkiadakis, E; Heindl, M; Hughes, E; Kaplan, S; Kunnawalkam Elayavalli, R; Kyriacou, S; Lath, A; Montalvo, R; Nash, K; Osherson, M; Saka, H; Salur, S; Schnetzer, S; Sheffield, D; Somalwar, S; Stone, R; Thomas, S; Thomassen, P; Walker, M; Zhou, B; Delannoy, A G; Foerster, M; Heideman, J; Riley, G; Rose, K; Spanier, S; Thapa, K; Bouhali, O; Castaneda Hernandez, A; Celik, A; Dalchenko, M; De Mattia, M; Delgado, A; Dildick, S; Eusebi, R; Gilmore, J; Huang, T; Kamon, T; Mueller, R; Pakhotin, Y; Patel, R; Perloff, A; Perniè, L; Rathjens, D; Safonov, A; Tatarinov, A; Ulmer, K A; Akchurin, N; Damgov, J; De Guio, F; Dudero, P R; Faulkner, J; Gurpinar, E; Kunori, S; Lamichhane, K; Lee, S W; Libeiro, T; Peltola, T; Undleeb, S; Volobouev, I; Wang, Z; Greene, S; Gurrola, A; Janjam, R; Johns, W; Maguire, C; Melo, A; Ni, H; Sheldon, P; Tuo, S; Velkovska, J; Xu, Q; Arenton, M W; Barria, P; Cox, B; Hirosky, R; Ledovskoy, A; Li, H; Neu, C; Sinthuprasith, T; Sun, X; Wang, Y; Wolfe, E; Xia, F; Harr, R; Karchin, P E; Sturdy, J; Zaleski, S; Brodski, M; Buchanan, J; Caillol, C; Dasu, S; Dodd, L; Duric, S; Gomber, B; Grothe, M; Herndon, M; Hervé, A; Hussain, U; Klabbers, P; Lanaro, A; Levine, A; Long, K; Loveless, R; Pierro, G A; Polese, G; Ruggles, T; Savin, A; Smith, N; Smith, W H; Taylor, D; Woods, N

2017-12-01

A search for a signal consistent with the type-III seesaw mechanism in events with three or more electrons or muons is presented. The data sample consists of proton-proton collisions at sqrt[s]=13 TeV collected by the CMS experiment at the LHC in 2016 and corresponds to an integrated luminosity of 35.9 fb^{-1}. Selection criteria based on the number of leptons and the invariant mass of oppositely charged lepton pairs are used to distinguish the signal from the standard model background. The observations are consistent with the expectations from standard model processes. The results are used to place limits on the production of heavy fermions of the type-III seesaw model as a function of the branching ratio to each lepton flavor. In the scenario of equal branching fractions to each lepton flavor, heavy fermions with masses below 840 GeV are excluded. This is the most sensitive probe to date of the type-III seesaw mechanism.
Effects of Helicobacter pylori infection and long-term proton pump inhibitor use on enterochromaffin-like cells

Science.gov (United States)

Bektaş, Mehmet; Saraç, Nurşen; Çetinkaya, Hülya; Törüner, Murat; Erdemli, Esra; Keskin, Onur; Soykan, İrfan; Oktay, Esen Ismet; Korkut, Esin; Üstün, Yusuf; Bahar, Kadir

2012-01-01

Background Excessive release of gastrin leads to hypertrophy and hyperplasia of enterochromaffin-like cells (ECL) and prolonged stimulation of these cells causes functional impairment. The purpose of this study was to investigate the effect of Helicobacter pylori (H. pylori) infection and long-term proton pump inhibitors (PPI) use on ECL cells. Methods Fifteen patients who underwent endoscopy because of dyspeptic symptoms were enrolled in the present study. Biopsies were taken from corpus and antrum and existence of H. pylori was investigated with culture, cytology and CLOtest. The patients were divided into 3 groups. Group-A: H. pylori-negative, never treated previously with PPI; Group-B: H. pylori-positive, never treated previously with PPI; and group-C: H. pylori-negative and continuously treated with PPI for more than 6 months before the subject recruitment period. The features of ECL cell in oxyntic glands were examined with electron microscopy on biopsy specimens. Results ECL cells were completely normal in Group A. In group B, moderate hyperplasia and vacuolization was seen in ECL cells. In group C, ECL cell hyperplasia was observed and vacuoles with greater amounts of granules in enlarged vesicles were found more intensely in cytoplasm. Conclusion The use of PPI for a long period of time and presence of H. pylori infection are risk factors for ECL hyperplasia. PMID:24714139
Gender differences in symptoms in partial responders to proton pump inhibitors for gastro-oesophageal reflux disease.

Science.gov (United States)

Vakil, N; Niklasson, A; Denison, H; Rydén, A

2015-10-01

Gender differences may exist in the symptom experience of patients with gastro-oesophageal reflux disease (GERD) who have a partial response to proton pump inhibitors (PPIs). The purpose of this study was to analyse gender differences in partial responders to PPIs. Patients with GERD who responded partially to PPIs (n = 580; NCT00703534) completed the Reflux Symptom Questionnaire 7-day recall (RESQ-7) and the Gastrointestinal Symptom Rating Scale (GSRS). Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale. Women had significantly higher RESQ-7 domain scores than men for Heartburn (frequency: 4.3 vs 3.9; intensity: 3.1 vs 2.8), Burping (frequency: 4.9 vs 4.4; intensity: 3.1 vs 2.8) and Hoarseness, cough and difficulty swallowing (frequency: 2.6 vs 2.2; intensity: 1.8 vs 1.5), and had higher GSRS domain discomfort scores than men for Abdominal pain (3.51 vs 3.23), Indigestion (3.80 vs 3.45) and Constipation (2.69 vs 2.17) (all p < 0.05). Anxiety and depression were significantly more prevalent in women than in men. In this population of partial responders, women had more frequent/intense heartburn and extra-oesophageal symptoms and more discomfort from abdominal pain, indigestion and constipation than men. Comorbid anxiety and depression may contribute to the increased symptom burden in women.
Clinical usefulness of limited sampling strategies for estimating AUC of proton pump inhibitors.

Science.gov (United States)

Niioka, Takenori

2011-03-01

Cytochrome P450 (CYP) 2C19 (CYP2C19) genotype is regarded as a useful tool to predict area under the blood concentration-time curve (AUC) of proton pump inhibitors (PPIs). In our results, however, CYP2C19 genotypes had no influence on AUC of all PPIs during fluvoxamine treatment. These findings suggest that CYP2C19 genotyping is not always a good indicator for estimating AUC of PPIs. Limited sampling strategies (LSS) were developed to estimate AUC simply and accurately. It is important to minimize the number of blood samples because of patient's acceptance. This article reviewed the usefulness of LSS for estimating AUC of three PPIs (omeprazole: OPZ, lansoprazole: LPZ and rabeprazole: RPZ). The best prediction formulas in each PPI were AUC(OPZ)=9.24 x C(6h)+2638.03, AUC(LPZ)=12.32 x C(6h)+3276.09 and AUC(RPZ)=1.39 x C(3h)+7.17 x C(6h)+344.14, respectively. In order to optimize the sampling strategy of LPZ, we tried to establish LSS for LPZ using a time point within 3 hours through the property of pharmacokinetics of its enantiomers. The best prediction formula using the fewest sampling points (one point) was AUC(racemic LPZ)=6.5 x C(3h) of (R)-LPZ+13.7 x C(3h) of (S)-LPZ-9917.3 x G1-14387.2×G2+7103.6 (G1: homozygous extensive metabolizer is 1 and the other genotypes are 0; G2: heterozygous extensive metabolizer is 1 and the other genotypes are 0). Those strategies, plasma concentration monitoring at one or two time-points, might be more suitable for AUC estimation than reference to CYP2C19 genotypes, particularly in the case of coadministration of CYP mediators.
Survey of findings in patients having persistent heartburn on proton pump inhibitor therapy.

Science.gov (United States)

Mandaliya, R; DiMarino, A J; Cohen, S

2016-01-01

In patients with refractory heartburn while on proton pump inhibitor (PPI) therapy, changing drugs or increasing treatment to a twice a day (b.i.d.) dose has become a common practice. This study aims to study patients with persistent heartburn while on PPI therapy and to determine if persistent symptom indicates the need for more aggressive or different therapy. A retrospective review of impedance-pH tracings on PPI therapy (q.d. or b.i.d.) for patients with persistent heartburn was performed. DeMeester score, impedance, and symptom sensitive index (SSI) were used as indices. Statistical analyses were performed using chi-squared test with Yates correction and paired t-test. One hundred consecutive patients, (female 50%, male 50%, mean age 54 [range 16-83] years) were studied on q.d. (n = 45) or b.i.d. PPI (n = 55). Only 20% of the patients had abnormal DeMeester score; 41% had an abnormal impedance score and 56% had abnormal SSI; 29% had all indices normal. There was no difference between patients taking q.d. versus b.i.d. PPI for abnormal DeMeester score (22 vs. 18%), impedance (38 vs. 44%) and SSI (53 vs. 58%); P = 0.80, 0.69, and 0.77, respectively. In 56 patients with positive SSI, symptoms were due to acid reflux in 8 (14%) patients, nonacid reflux in 31 (55%) patients, and combined acid and nonacid reflux in 17 (30%) patients. Patients with persistent heartburn on PPI therapy show a variety of disorders: (i) acid reflux (20%); (ii) nonacid reflux (26%); (iii) positive SSI (56%); (iv) all normal indices (29%). These studies indicate that persistent heartburn on PPI therapy is a complex problem that may not respond to simply increasing acid inhibition. © 2014 International Society for Diseases of the Esophagus.
Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy

OpenAIRE

Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

2016-01-01

Background/Aims The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups recei...
Rapid Convergence of Energy and Free Energy Profiles with Quantum Mechanical Size in Quantum Mechanical-Molecular Mechanical Simulations of Proton Transfer in DNA.

Science.gov (United States)

Das, Susanta; Nam, Kwangho; Major, Dan Thomas

2018-03-13

In recent years, a number of quantum mechanical-molecular mechanical (QM/MM) enzyme studies have investigated the dependence of reaction energetics on the size of the QM region using energy and free energy calculations. In this study, we revisit the question of QM region size dependence in QM/MM simulations within the context of energy and free energy calculations using a proton transfer in a DNA base pair as a test case. In the simulations, the QM region was treated with a dispersion-corrected AM1/d-PhoT Hamiltonian, which was developed to accurately describe phosphoryl and proton transfer reactions, in conjunction with an electrostatic embedding scheme using the particle-mesh Ewald summation method. With this rigorous QM/MM potential, we performed rather extensive QM/MM sampling, and found that the free energy reaction profiles converge rapidly with respect to the QM region size within ca. ±1 kcal/mol. This finding suggests that the strategy of QM/MM simulations with reasonably sized and selected QM regions, which has been employed for over four decades, is a valid approach for modeling complex biomolecular systems. We point to possible causes for the sensitivity of the energy and free energy calculations to the size of the QM region, and potential implications.
Maternal response to two electric breast pumps

Science.gov (United States)

Mechanical characteristics of breast pumps have been shown to influence milk extraction and hormone release in laboratory settings. However, few studies evaluate impact of differences in pump design on long-term breastfeeding success. This study evaluated the impact of a novel pump design on milk ex...
Comparison of health care resource utilization and costs among patients with GERD on once-daily or twice-daily proton pump inhibitor therapy

Directory of Open Access Journals (Sweden)

Mody R

2013-04-01

Full Text Available Reema Mody,1 Debra Eisenberg,2 Likun Hou,2 Siddhesh Kamat,2 Joseph Singer,2 Lauren B Gerson3 1Takeda Pharmaceuticals International Inc, Deerfield, IL, 2HealthCore Inc, Wilmington, DE, 3Stanford University School of Medicine, Stanford, CA, USA Background: The purpose of this study was to assess differences in health care resource utilization and costs associated with once-daily and twice-daily proton pump inhibitor (PPI therapy. Most patients with gastroesophageal reflux disease (GERD achieve symptom control on once-daily PPI therapy, but approximately 20%–30% require twice-daily dosing. Methods: Patients were ≥18 years of age with at least one medical claim for GERD and at least two PPI claims from HealthCore's Integrated Research Database (HIRDSM during 2004–2009. Patients were continuously eligible for 12 months before and after the index date (date of first PPI claim. Based on PPI dosing throughout the post-index period (quantity of medication dispensed/number of days supply, patients were classified as once-daily (dose ≤ 1.5 pills per day or twice-daily (≥1.5 PPI users. Results: The study cohort included 248,386 patients with GERD (mean age 52.8 ± 13.93 years, 56% females of whom 90% were once-daily and 10% were twice-daily PPI users. The Deyo-Charlson Comorbidity Index for once-daily and twice-daily PPI users was 0.70 ± 1.37 and 0.89 ± 1.54, respectively (P < 0.05. More once-daily patients had claims for Barrett's esophagus (5% versus 2%, P < 0.0001 than twice-daily patients. Post-index, higher proportions of twice-daily patients had at least one GERD-related inpatient visit (7% versus 5%, outpatient visit (60% versus 49%, and office visit (48% versus 38% versus once-daily patients (P < 0.0001. Mean total GERD-related health care costs were $2065 ± $6636 versus $3749 ± $11,081 for once-daily and twice-daily PPI users, respectively (P < 0.0001. Conclusion: Patients receiving twice-daily PPI therapy were likely to have more
The proton pump inhibitor, omeprazole, but not lansoprazole or pantoprazole, is a metabolism-dependent inhibitor of CYP2C19: implications for coadministration with clopidogrel.

Science.gov (United States)

Ogilvie, Brian W; Yerino, Phyllis; Kazmi, Faraz; Buckley, David B; Rostami-Hodjegan, Amin; Paris, Brandy L; Toren, Paul; Parkinson, Andrew

2011-11-01

As a direct-acting inhibitor of CYP2C19 in vitro, lansoprazole is more potent than omeprazole and other proton pump inhibitors (PPIs), but lansoprazole does not cause clinically significant inhibition of CYP2C19 whereas omeprazole does. To investigate this apparent paradox, we evaluated omeprazole, esomeprazole, R-omeprazole, lansoprazole, and pantoprazole for their ability to function as direct-acting and metabolism-dependent inhibitors (MDIs) of CYP2C19 in pooled human liver microsomes (HLM) as well as in cryopreserved hepatocytes and recombinant CYP2C19. In HLM, all PPIs were found to be direct-acting inhibitors of CYP2C19 with IC(50) values varying from 1.2 μM [lansoprazole; maximum plasma concentration (C(max)) = 2.2 μM] to 93 μM (pantoprazole; C(max) = 6.5 μM). In addition, we identified omeprazole, esomeprazole, R-omeprazole, and omeprazole sulfone as MDIs of CYP2C19 (they caused IC(50) shifts after a 30-min preincubation with NADPH-fortified HLM of 4.2-, 10-, 2.5-, and 3.2-fold, respectively), whereas lansoprazole and pantoprazole were not MDIs (IC(50) shifts lansoprazole, or pantoprazole, as irreversible (or quasi-irreversible) MDIs of CYP2C19. These results have important implications for the mechanism of the clinical interaction reported between omeprazole and clopidogrel, as well as other CYP2C19 substrates.

Reversible oxidative modification: a key mechanism of Na+-K+ pump regulation.

Science.gov (United States)

Figtree, Gemma A; Liu, Chia-Chi; Bibert, Stephanie; Hamilton, Elisha J; Garcia, Alvaro; White, Caroline N; Chia, Karin K M; Cornelius, Flemming; Geering, Kaethi; Rasmussen, Helge H

2009-07-17

Angiotensin II (Ang II) inhibits the cardiac sarcolemmal Na(+)-K(+) pump via protein kinase (PK)C-dependent activation of NADPH oxidase. We examined whether this is mediated by oxidative modification of the pump subunits. We detected glutathionylation of beta(1), but not alpha(1), subunits in rabbit ventricular myocytes at baseline. beta(1) Subunit glutathionylation was increased by peroxynitrite (ONOO(-)), paraquat, or activation of NADPH oxidase by Ang II. Increased glutathionylation was associated with decreased alpha(1)/beta(1) subunit coimmunoprecipitation. Glutathionylation was reversed after addition of superoxide dismutase. Glutaredoxin 1, which catalyzes deglutathionylation, coimmunoprecipitated with beta(1) subunit and, when included in patch pipette solutions, abolished paraquat-induced inhibition of myocyte Na(+)-K(+) pump current (I(p)). Cysteine (Cys46) of the beta(1) subunit was the likely candidate for glutathionylation. We expressed Na(+)-K(+) pump alpha(1) subunits with wild-type or Cys46-mutated beta(1) subunits in Xenopus oocytes. ONOO(-) induced glutathionylation of beta(1) subunit and a decrease in Na(+)-K(+) pump turnover number. This was eliminated by mutation of Cys46. ONOO(-) also induced glutathionylation of the Na(+)-K(+) ATPase beta(1) subunit from pig kidney. This was associated with a approximately 2-fold decrease in the rate-limiting E(2)-->E(1) conformational change of the pump, as determined by RH421 fluorescence. We propose that kinase-dependent regulation of the Na(+)-K(+) pump occurs via glutathionylation of its beta(1) subunit at Cys46. These findings have implications for pathophysiological conditions characterized by neurohormonal dysregulation, myocardial oxidative stress and raised myocyte Na(+) levels.
Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics

DEFF Research Database (Denmark)

Schjerning Olsen, Anne-Marie; Lindhardsen, Jesper; Gislason, Gunnar H

2015-01-01

STUDY QUESTION: What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)? METHODS: This was a nationwide cohort study based on linked.......95) regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. The main limitation of the study is its observational non-randomised design. The results suggest that PPI treatment probably has a beneficial effect regardless of underlying gastrointestinal risk and that when NSAIDs cannot...... of NSAID, and type of PPI used. FUNDING, COMPETING INTERESTS, DATA SHARING: AMSO has received a grant from the Danish Council of Independent Research (grant 12-132760). GHG is supported by an unrestricted research scholarship from the Novo Nordisk Foundation....
Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics

DEFF Research Database (Denmark)

Schjerning Olsen, Anne-Marie; Lindhardsen, Jesper; Gislason, Gunnar H

2015-01-01

STUDY QUESTION: What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)? METHODS: This was a nationwide cohort study based on linked...... plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models. STUDY ANSWER AND LIMITATIONS: The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated...... gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0...
Analysis of hypocycloid drive application in a high-pressure fuel pump

Directory of Open Access Journals (Sweden)

Bor Mateusz

2017-01-01

Full Text Available This paper undertakes the problem of applying a hypocycloid mechanism in the drive of pumping sections of high-pressure pumps for Diesel combustion engines. The authors have reviewed existing pump drive mechanisms, analyzed the weak links in existing solutions and discussed the latest trends in common rail systems. Further sections describe the design of a pump utilizing a hypocycloid mechanism, demonstrate beneficial functional features and present selected results of the assembly’s dynamic simulation. As a result of work, a pump model was developed, with operating parameters that do not deviate from those of the latest solutions of leading manufacturers, simultaneously eliminating the greatest flaws of existing pumps that lead to their premature wear.
Perturbation of the Electron Transport Mechanism by Proton Intercalation in Nanoporous TiO2 Films

Energy Technology Data Exchange (ETDEWEB)

Halverson, A. F.; Zhu, K.; Erslev, P. T.; Kim, J. Y.; Neale, N. R.; Frank, A. J.

2012-04-11

This study addresses a long-standing controversy about the electron-transport mechanism in porous metal oxide semiconductor films that are commonly used in dye-sensitized solar cells and related systems. We investigated, by temperature-dependent time-of-flight measurements, the influence of proton intercalation on the electron-transport properties of nanoporous TiO{sub 2} films exposed to an ethanol electrolyte containing different percentages of water (0-10%). These measurements revealed that increasing the water content in the electrolyte led to increased proton intercalation into the TiO{sub 2} films, slower transport, and a dramatic change in the dependence of the thermal activation energy (E{sub a}) of the electron diffusion coefficient on the photogenerated electron density in the films. Random walk simulations based on a microscopic model incorporating exponential conduction band tail (CBT) trap states combined with a proton-induced shallow trap level with a long residence time accounted for the observed effects of proton intercalation on E{sub a}. Application of this model to the experimental results explains the conditions under which E{sub a} dependence on the photoelectron density is consistent with multiple trapping in exponential CBT states and under which it appears at variance with this model.
Development of an electro-osmotic heat pump

NARCIS (Netherlands)

Stoel, J.P. van der; Oostendorp, P.A.

1999-01-01

The majority of heat pumps and refrigerators is driven by a mechanical compressor. Although they usually function very well, the search for new and in some cases better heat pumping concepts continues. One of the topics in this field is the development of an electro-osmotic heat pump. As each
Evaluation of reciprocating electromagnetic air pumping for portable PEMFC

International Nuclear Information System (INIS)

Kwon, Kilsung; Kang, Ho; Kang, Seongwon; Kim, Daejoong

2013-01-01

In this paper, we present a proton exchange membrane fuel cell (PEMFC) integrated with an electromagnetic (EM) air pump. The EM air pump provides the PEMFC with air by reciprocating motions of the permanent magnet attached to a flexible membrane. We performed a parametric study to decide the optimal dimensions of the reciprocating EM air pump. The effects of various operating parameters on the EM air pump were investigated with the root-mean-square (RMS) flow rate and current. A core with a higher relative permeability shows better performance. The RMS current linearly increases with the applied voltage and shows no dependence on the frequency. The RMS flow rate also increases with the voltage. The RMS flow rate per power consumption is highest at the frequency around 20 Hz and decreases as the applied voltage increases. When the reciprocating EM air pump was used to supply air to the portable PEMFC, it was found that the power density of the PEMFC increases with the applied voltage and shows the highest performance at the frequency of 10 Hz. We compared the performance of the PEMFC between the flow meter and the EM air pump used as an air supplier. About 81% of the output power using the flow meter was obtained when the EM air pump is operated at the applied voltage of 5 V. The parasitic power ratio reaches at its minimum value about 0.1 with an EM applied voltage of 0.25V. (paper)
Proton irradiation effects on organic polymers

International Nuclear Information System (INIS)

Seguchi, T.; Sasuga, T.; Kawakami, W.; Hagiwara, M.; Kohno, I.; Kamitsubo, H.

1987-01-01

Organic polymer films(100 μm thickness) of polyethylene, polypropylene, polyethyleneterephtalate, and polyethersulfone were irradiated by protons of 8 MeV using a cyclotron, and their radiation effects were investigated by the changes of mechanical properties. In order to irradiate protons uniformly over wide area of polymer films, specimens were scanned during proton irradiation using a special apparatus. The absorbed dose was measured by CTA and RCD film dosimeters, and can be determined that 1 μC/cm 2 of 8 MeV proton fluence is equivalent to 54 kGy. For polyethylene and polypropylene, there was no significant difference between proton and electron irradiation for same doses. However, for polyethersulfone the decay of mechanical property was observed to be less than that of irradiation by electron. (author)
Drug Repositioning of Proton Pump Inhibitors for Enhanced Efficacy and Safety of Cancer Chemotherapy

Directory of Open Access Journals (Sweden)

Kenji Ikemura

2017-12-01

Full Text Available Proton pump inhibitors (PPIs, H+/K+-ATPase inhibitors, are the most commonly prescribed drugs for the treatment of gastroesophageal reflux and peptic ulcer diseases; they are highly safe and tolerable. Since PPIs are frequently used in cancer patients, studies investigating interactions between PPIs and anticancer agents are of particular importance to achieving effective and safe cancer chemotherapy. Several studies have revealed that PPIs inhibit not only the H+/K+-ATPase in gastric parietal cells, but also the vacuolar H+-ATPase (V-ATPase overexpressed in tumor cells, as well as the renal basolateral organic cation transporter 2 (OCT2 associated with pharmacokinetics and/or renal accumulation of various drugs, including anticancer agents. In this mini-review, we summarize the current knowledge regarding the impact of PPIs on the efficacy and safety of cancer chemotherapeutics via inhibition of targets other than the H+/K+-ATPase. Co-administration of clinical doses of PPIs protected kidney function in patients receiving cisplatin and fluorouracil, presumably by decreasing accumulation of cisplatin in the kidney via OCT2 inhibition. In addition, co-administration or pretreatment with PPIs could inhibit H+ transport via the V-ATPase in tumor cells, resulting in lower extracellular acidification and intracellular acidic vesicles to enhance the sensitivity of the tumor cells to the anticancer agents. In the present mini-review, we suggest that PPIs enhance the efficacy and safety of anticancer agents via off-target inhibition (e.g., of OCT2 and V-ATPase, rather than on-target inhibition of the H+/K+-ATPase. The present findings should provide important information to establish novel supportive therapy with PPIs during cancer chemotherapy.
Esophageal mucosal breaks in gastroesophageal reflux disease partially responsive to proton pump inhibitor therapy.

Science.gov (United States)

Shaheen, Nicholas J; Denison, Hans; Björck, Karin; Silberg, Debra G

2013-04-01

Approximately 20-30% of patients with gastroesophageal reflux disease (GERD) do not experience complete symptom resolution during proton pump inhibitor (PPI) therapy. The aim of this study was to determine the prevalence of esophageal mucosal breaks among patients who have a partial response to PPI therapy. This was an analysis of data from a phase 2b clinical trial carried out to assess the efficacy and safety of a reflux inhibitor, lesogaberan (AZD3355), as an add-on to PPI therapy in this patient population (clinicaltrials.gov reference: NCT01005251). A total of 661 patients with persistent GERD symptoms who had received a minimum of 4 weeks of PPI therapy were included in the study. The prevalence of esophageal mucosal breaks was assessed according to (i) the most recent endoscopy results from within the previous 24 months, if available ("historical" endoscopies), and (ii) the results of endoscopies performed at study baseline ("baseline" endoscopies). Baseline endoscopies were not carried out in patients who had a historical endoscopy showing an absence of esophageal mucosal breaks. Historical endoscopy results were available for 244 patients, of whom 48 (19.7%) had esophageal mucosal breaks. Baseline endoscopies were carried out in 465 patients, of whom 146 (31.4%) had esophageal mucosal breaks. Sensitivity analyses showed a prevalence of esophageal mucosal breaks of 20-30%. In both the historical and baseline endoscopies, most esophageal mucosal breaks were Los Angeles grades A or B. In patients with GERD symptoms partially responsive to PPI therapy, mild-to-moderate severity esophageal mucosal breaks are common (prevalence 20-30%), and may contribute to symptom etiology.
TFTR ultrahigh-vacuum pumping system incorporating mercury diffusion pumps

International Nuclear Information System (INIS)

Sink, D.A.; Sniderman, M.

1976-06-01

The TFTR vacuum vessel will have a system of four 61 cm diameter mercury diffusion pumps to provide a base pressure in the 10 -8 to 10 -9 Torr range as well as a low impurity level within the vessel. The system, called the Torus Vacuum Pumping System (TVPS), will be employed with the aid of an occasional 250 0 C bakeout in situ as well as periodic applications of aggressive discharge cleaning. The TVPS is an ultrahigh-vacuum (UHV) system using no elastomers as well as being a closed system with respect to tritium or any tritiated gases. The backing system employing approximately 75 all-metal isolation valves is designed with the features of redundancy and flexibility employed in a variety of ways to meet the fundamental requirements and functions enumerated for the TVPS. Since the design, is one which is a modification of the conceptual design of the TVPS, those features which have changed are discussed. Calculations are presented for the major performance parameters anticipated for the TVPS and include conductances, effective pumping speeds, base pressures, operating parameters, getter pump parameters, and calculations of time constants associated with leak checking. Modifications in the vacuum pumping system for the guard regions on the twelve bellows sections are presented so that it is compatible with the main TVPS. The bellows pumping system consists of a mechanical pump unit, a zirconium aluminum getter pump unit and a residual gas analyzer. The control and management of the TVPS is described with particular attention given to providing both manual and automatic control at a local station and at the TFTR Central Control. Such operations as testing, maintenance, leak checking, startup, bakeout, and various other operations are considered in some detail. Various aspects related to normal pulsing, discharge cleaning, non-tritium operations and tritium operations are also taken into consideration. A cost estimate is presented
Detection of pump degradation

International Nuclear Information System (INIS)

Casada, D.

1994-01-01

There are a variety of stressors that can affect the operation of centrifugal pumps. Although these general stressors are active in essentially all centrifugal pumps, the stressor level and the extent of wear and degradation can vary greatly. Parameters that affect the extent of stressor activity are manifold. In order to assure the long-term operational readiness of a pump, it is important to both understand the nature and magnitude of the specific degradation mechanisms and to monitor the performance of the pump. The most commonly applied method of monitoring the condition of not only pumps, but rotating machinery in general, is vibration analysis. Periodic or continuous spectral vibration analysis is a cornerstone of most pump monitoring programs. In the nuclear industry, non-spectral vibration monitoring of safety-related pumps is performed in accordance with the ASME code. Although vibration analysis has dominated the condition monitoring field for many years, there are other measures that have been historically used to help understand pump condition: advances in historically applied technologies and developing technologies offer improved monitoring capabilities. The capabilities of several technologies (including vibration analysis, dynamic pressure analysis, and motor power analysis) to detect the presence and magnitude of both stressors and resultant degradation are discussed
Heat pumping in nanomechanical systems

OpenAIRE

Chamon, Claudio; Mucciolo, Eduardo R.; Arrachea, Liliana; Capaz, Rodrigo B.

2010-01-01

We propose using a phonon pumping mechanism to transfer heat from a cold to a hot body using a propagating modulation of the medium connecting the two bodies. This phonon pump can cool nanomechanical systems without the need for active feedback. We compute the lowest temperature that this refrigerator can achieve.
Detection of pump degradation

International Nuclear Information System (INIS)

Casada, D.

1995-01-01

There are a variety of stressors that can affect the operation of centrifugal pumps. Although these general stressors are active in essentially all centrifugal pumps, the stressor level and the extent of wear and degradation can vary greatly. Parameters that affect the extent of stressor activity are manifold. In order to assure the long-term operational readiness of a pump, it is important to both understand the nature and magnitude of the specific degradation mechanisms and to monitor the performance of the pump. The most commonly applied method of monitoring the condition of not only pumps, but rotating machinery in general, is vibration analysis. Periodic or continuous special vibration analysis is a cornerstone of most pump monitoring programs. In the nuclear industry, non-spectral vibration monitoring of safety-related pumps is performed in accordance with the ASME code. Pump head and flow rate are also monitored, per code requirements. Although vibration analysis has dominated the condition monitoring field for many years, there are other measures that have been historically used to help understand pump condition; advances in historically applied technologies and developing technologies offer improved monitoring capabilities. The capabilities of several technologies (including vibration analysis, dynamic pressure analysis, and motor power analysis) to detect the presence and magnitude of both stressors and resultant degradation are discussed
Quantum-mechanical analysis of amino acid residues function in the proton transport during F0F1-ATP synthase catalytic cycle

Science.gov (United States)

Ivontsin, L. A.; Mashkovtseva, E. V.; Nartsissov, Ya R.

2017-11-01

Implications of quantum-mechanical approach to the description of proton transport in biological systems are a tempting subject for an overlapping of fundamental physics and biology. The model of proton transport through the integrated membrane enzyme FoF1-ATP synthase responsible for ATP synthesis was developed. The estimation of the mathematical expectation of the proton transfer time through the half-channel was performed. Observed set of proton pathways through the inlet half-channel showed the nanosecond timescale highly dependable of some amino acid residues. There were proposed two types of crucial amino acids: critically localized (His245) and being a part of energy conserving system (Asp119).
How It's Made - Polarized Proton Beam (444th Brookhaven Lecture)

International Nuclear Information System (INIS)

Zelenski, Anatoli

2008-01-01

Experiments with polarized beams at RHIC will provide fundamental tests of QCD, and the electro-weak interaction reveal the spin structure of the proton. Polarization asymmetries and parity violation are the strong signatures for identification of the fundamental processes, which are otherwise inaccessible. Such experiments require the maximum available luminosity and therefore polarization must be obtained as an extra beam quality without sacrificing intensity. There are proposals to polarize the high-energy proton beam in the storage rings by the Stern-Gerlach effect or spin-filter techniques. But so far, the only practically available option is acceleration of the polarized beam produced in the source and taking care of polarization survival during acceleration and storage. Two major innovations -- the 'Siberian Snake' technique for polarization preservation during acceleration and high current polarized proton sources make spin physics with the high-energy polarized beams feasible. The RHIC is the first high-energy collider, where the 'Siberian Snake' technique allowed of polarized proton beam acceleration up-to 250 GeV energy. The RHIC unique Optically Pumped Polarized Ion Source produces sufficient polarized beam intensity for complete saturation of the RHIC acceptance. This polarization technique is based on spin-transfer collisions between a proton or atomic hydrogen beam of a few keV beam energy and optically pumped alkali metal vapors. From the first proposal and feasibility studies to the operational source this development can be considered as example of successful unification of individual scientists ingenuity, international collaboration and modern technology application for creation of a new polarization technique, which allowed of two-to-three order of magnitude polarized beam intensity increase sufficient for loading the RHIC to its full capacity for polarization studies.
Reaction pathways of photoexcited retinal in proteorhodopsin studied by pump-dump-probe spectroscopy

NARCIS (Netherlands)

Rupenyan, A.; van Stokkum, I.H.M.; Arents, J.C.; van Grondelle, R.; Hellingwerf, K.J.; Groot, M.L.

2009-01-01

Proteorhodopsin (pR) is a membrane-embedded proton pump from the microbial rhodopsin family. Light absorption by its retinal chromophore initiates a photocycle, driven by trans/cis isomerization on the femtosecond to picosecond time scales. Here, we report a study on the photoisomerization dynamics
Sodium pumping: pump problems

International Nuclear Information System (INIS)

Guer, M.; Guiton, P.

Information on sodium pumps for LMFBR type reactors is presented concerning ring pump design, pool reactor pump design, secondary pumps, sodium bearings, swivel joints of the oscillating annulus, and thermal shock loads
CRBRP sodium circulating pump design evaluation

International Nuclear Information System (INIS)

Marrujo, F.; Cook, M.; Manners, L.; Cothran, H.

1977-12-01

The following topics are discussed: (1) primary sodium pump design concept; (2) pump level control system; (3) resolution of design problems in stress analysis, dynamics analysis, and mechanical design; (4) model testing; (5) planned performance tests; and (6) fabrication status
Quantum-mechanical predictions of DNA and RNA ionization by energetic proton beams.

Science.gov (United States)

Galassi, M E; Champion, C; Weck, P F; Rivarola, R D; Fojón, O; Hanssen, J

2012-04-07

Among the numerous constituents of eukaryotic cells, the DNA macromolecule is considered as the most important critical target for radiation-induced damages. However, up to now ion-induced collisions on DNA components remain scarcely approached and theoretical support is still lacking for describing the main ionizing processes. In this context, we here report a theoretical description of the proton-induced ionization of the DNA and RNA bases as well as the sugar-phosphate backbone. Two different quantum-mechanical models are proposed: the first one based on a continuum distorted wave-eikonal initial state treatment and the second perturbative one developed within the first Born approximation with correct boundary conditions (CB1). Besides, the molecular structure information of the biological targets studied here was determined by ab initio calculations with the Gaussian 09 software at the restricted Hartree-Fock level of theory with geometry optimization. Doubly, singly differential and total ionization cross sections also provided by the two models were compared for a large range of incident and ejection energies and a very good agreement was observed for all the configurations investigated. Finally, in comparison with the rare experiment, we have noted a large underestimation of the total ionization cross sections of uracil impacted by 80 keV protons,whereas a very good agreement was shown with the recently reported ionization cross sections for protons on adenine, at both the differential and the total scale.

Polarized proton Target-III operators manual, revision A

International Nuclear Information System (INIS)

Hill, D.; Moretti, A.; Onesto, F.; Rynes, P.

1976-04-01

A revision is given of a manual containing standard operating procedures for the vacuum, cryogenic, and electronic systems of a polarized proton target. The discussion includes the target cryostat, the 3 He and 4 He pumping systems, remote monitors and controls, the microwave system, the magnet and power supply, the computerized polarization monitor, the 4 He liquifier and gas recovery system, and miscellaneous auxiliary equipment
Evaluation of personal air sampling pumps

International Nuclear Information System (INIS)

Ritter, P.D.; Novick, V.J.; Alvarez, J.L.; Huntsman, B.L.

1987-01-01

Personal air samplers are used to more conveniently obtain breathing zone samples from individuals over periods of several hours. Personal air sampling pumps must meet minimum performance levels under all working conditions to be suitable for use in radiation protection programs. In addition, the pumps should be simple to operate and as comfortable to wear as possible. Ten models of personal air sampling pumps were tested to evaluate their mechanical performance and physical characteristics. The pumps varied over a wide range in basic performance and operating features. Some of the pumps were found to have adequate performance for use in health physics air sampling applications. 3 references, 2 figures, 5 tables
The Plasma Membrane Calcium Pump

Science.gov (United States)

Rasmussen, H.

1983-01-01

Three aspect of cellular calcium metabolism in animal cells was discussed including the importance of the plasma membrane in calcium homeostasis, experiments dealing with the actual mechanism of the calcium pump, and the function of the pump in relationship to the mitochondria and to the function of calmodulin in the intact cell.
Esophageal Baseline Impedance Reflects Mucosal Integrity and Predicts Symptomatic Outcome With Proton Pump Inhibitor Treatment.

Science.gov (United States)

Xie, Chenxi; Sifrim, Daniel; Li, Yuwen; Chen, Minhu; Xiao, Yinglian

2018-01-30

Esophageal baseline impedance, which is decreased in gastroesophageal reflux disease (GERD) patients, is related to the severity of acid reflux and the integrity of the esophageal mucosa. The study aims to compare the baseline impedance and the dilated intercellular spaces (DIS) within patients with typical reflux symptoms and to evaluate the correlation of baseline impedance with DIS, esophageal acid exposure, as well as the efficacy of proton pump inhibitor (PPI) treatment. Ninety-two patients and 10 healthy controls were included in the study. Erosive esophagitis (EE) was defined by esophageal mucosal erosion under upper endoscopy. Patients without mucosa erosion were divided into groups with pathologic acid reflux (non-erosive reflux disease [NERD]) or with hypersensitive esophagus. The biopsies of esophageal mucosa were taken 2-4 cm above the gastroesophageal junction Z-line during upper endoscopy for DIS measurement. All the patients received esomeprazole 20 mg twice-daily treatment for 8 weeks. The efficacy of esomeprazole was evaluated among all patients. The intercellular spaces were dilated in both EE and NERD patients ( P baseline impedance was decreased in both EE patients and NERD patients, and negatively correlated to the acid exposure time ( r = -0.527, P baseline impedance ( r = -0.230, P Baseline impedance > 1764 Ω" was an independent predictor for PPI failure (OR, 11.9; 95% CI, 2.4-58.9; P baseline impedance was observed in patients with mucosa erosion or pathological acid reflux. The baseline impedance reflected the mucosal integrity, it was more sensitive to esophageal acid exposure. Patients with high impedance might not benefit from the PPI treatment.
Ultrafast proton shuttling in Psammocora cyan fluorescent protein.

Science.gov (United States)

Kennis, John T M; van Stokkum, Ivo H M; Peterson, Dayna S; Pandit, Anjali; Wachter, Rebekka M

2013-09-26

Cyan, green, yellow, and red fluorescent proteins (FPs) homologous to green fluorescent protein (GFP) are used extensively as model systems to study fundamental processes in photobiology, such as the capture of light energy by protein-embedded chromophores, color tuning by the protein matrix, energy conversion by Förster resonance energy transfer (FRET), and excited-state proton transfer (ESPT) reactions. Recently, a novel cyan fluorescent protein (CFP) termed psamFP488 was isolated from the genus Psammocora of reef building corals. Within the cyan color class, psamFP488 is unusual because it exhibits a significantly extended Stokes shift. Here, we applied ultrafast transient absorption and pump-dump-probe spectroscopy to investigate the mechanistic basis of psamFP488 fluorescence, complemented with fluorescence quantum yield and dynamic light scattering measurements. Transient absorption spectroscopy indicated that, upon excitation at 410 nm, the stimulated cyan emission rises in 170 fs. With pump-dump-probe spectroscopy, we observe a very short-lived (110 fs) ground-state intermediate that we assign to the deprotonated, anionic chromophore. In addition, a minor fraction (14%) decays with 3.5 ps to the ground state. Structural analysis of homologous proteins indicates that Glu-167 is likely positioned in sufficiently close vicinity to the chromophore to act as a proton acceptor. Our findings support a model where unusually fast ESPT from the neutral chromophore to Glu-167 with a time constant of 170 fs and resulting emission from the anionic chromophore forms the basis of the large psamFP488 Stokes shift. When dumped to the ground state, the proton on neutral Glu is very rapidly shuttled back to the anionic chromophore in 110 fs. Proton shuttling in excited and ground states is a factor of 20-4000 faster than in GFP, which probably results from a favorable hydrogen-bonding geometry between the chromophore phenolic oxygen and the glutamate acceptor, possibly
40 CFR 65.107 - Standards: Pumps in light liquid service.

Science.gov (United States)

2010-07-01

... mechanical seal pumps. Each pump equipped with a dual mechanical seal system that includes a barrier fluid... million or greater for pumps in food/medical service; and (iii) 1,000 parts per million or greater for all... frequency of drips and to the sensor that indicates failure of the seal system, the barrier fluid system, or...
Mechanical pumps for liquid metals; Pompes mecaniques pour metaux liquides

Energy Technology Data Exchange (ETDEWEB)

Baumier, J; Gollion, H J [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1964-07-01

The pumping of liquid metals by centrifugal pumps poses two principal problems. These are hermetic sealing of the rotating shaft and, its guidance where immersed in liquid metal. The solutions to the problems used on 13 experimental pumps are given here. The resolution of the guidance problem consists in the majority of cases in the utilisation of hydrostatic bearings. Accordingly, a theoretical study was instituted for the first time to calculate the bearings of the earlier pumps. After this, an experimental study was carried out, to check the theory by water tests. A relation for bearing calculation of pumps with diffusers is proposed. Finally the influence of the bearing elasticity on the shafts critical speed is studied. (authors) [French] Le pompage des metaux liquides, par des pompes centrifuges, pose 2 principaux problemes, qui sont: d'une part, la realisation d'une excellente etancheite au passage de l'arbre, d'autre part, son guidage sur la partie immergee dans le metal liquide. Les solutions retenues pour resoudre ces problemes sur 13 pompes experimentees sont presentees. Le probleme du guidage de l'arbre, a dans la majorite des cas ete resolu en utilisant un palier hydrostatique, aussi l'etude en a d'abord ete approfondie de facon theorique pour calculer les paliers des premieres pompes, puis experimentale pour controler la theorie, en effectuant des essais a l'eau. On propose une relation pour calculer les paliers des pompes a diffuseurs. On a en outre effectue une etude de l'influence de l'elasticite du palier hydrostatique sur la vitesse critique de l'arbre. (auteurs)
Pumps and pump facilities. 2. ed.

International Nuclear Information System (INIS)

Bohl, W.; Bauerfeind, H.; Gutmann, G.; Leuschner, G.; Matthias, H.B.; Mengele, R.; Neumaier, R.; Vetter, G.; Wagner, W.

1981-01-01

This book deals with the common fundamental aspects of liquid pumps and gives an exemplary choice of the most important kinds of pumps. The scientific matter is dealt with by means of practical mathematical examples among other ways of presenting the matter. Survey of contents: Division on main operational data of pumps - pipe characteristics - pump characteristics - suction behaviour of the pumps - projecting and operation of rotary pumps - boiler feed pumps - reactor feed pumps - oscillating positive-displacement pumps - eccentric spiral pumps. (orig./GL) [de
Development of ANC-type empirical two-phase pump model for full size CANDU primary heat transport pump

International Nuclear Information System (INIS)

Chan, A.M.C.; Huynh, H.M.

2004-01-01

The development of an ANC-type empirical two-phase pump model for CANDU (Canadian Deuterium) reactor primary heat transport pumps is described in the present paper. The model was developed based on Ontario Hydro Technologies' full scale Darlington pump first quadrant test data. The functional form of the ANC model which is widely used was chosen to facilitate the implementation of the model into existing computer codes. The work is part of a bigger test program with the aims: (1) to produce high quality pump performance data under off-normal operating conditions using both full-size and model scale pumps; (2) to advance our basic understanding of the dominant mechanisms affecting pump performance based on more detailed local measurements; and (3) to develop a 'best-estimate' or improved pump model for use in reactor licensing and safety analyses. (author)
Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients

Science.gov (United States)

Nakagawa, Kenichiro; Koike, Tomoyuki; Iijima, Katsunori; Saito, Masahiro; Kikuchi, Hiroki; Hatta, Waku; Ara, Nobuyuki; Uno, Kaname; Asano, Naoki; Shimosegawa, Tooru

2015-01-01

AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease (NERD) patients. METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance - pH on rabeprazole. The symptom index (SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter. RESULTS: In 14 (40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes (46.7%) than in distal ones (5.7%) (P acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (38.5%) and distal ones (20.5%) (NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent (31.0%) than in distal reflux ones (3.3%) (P acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (29.4%) and distal ones (14.3%) (NS). CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy. PMID:26715820
Quarkonium production in high energyproton-proton and proton-nucleus collisions

Energy Technology Data Exchange (ETDEWEB)

del Valle, Z C; Corcella, G; Fleuret, F; Ferreiro, E G; Kartvelishvili, V; Kopeliovich, B; Lansberg, J P; Lourenco, C; Martinez, G; Papadimitriou, V; Satz, H; Scomparin, E; Ullrich, T; Teryaev, O; Vogt, R; Wang, J X

2011-03-14

We present a brief overview of the most relevant current issues related to quarkonium production in high energy proton-proton and proton-nucleus collisions along with some perspectives. After reviewing recent experimental and theoretical results on quarkonium production in pp and pA collisions, we discuss the emerging field of polarization studies. Afterwards, we report on issues related to heavy-quark production, both in pp and pA collisions, complemented by AA collisions. To put the work in broader perpectives, we emphasize the need for new observables to investigate the quarkonium production mechanisms and reiterate the qualities that make quarkonia a unique tool for many investigations in particle and nuclear physics.
Intermittency and Inflexibility Blister Pump Impress Factors

OpenAIRE

Mlakar, Boštjan; Zupančič, Cvetko

2011-01-01

Divisional centralized heating and cooling system, cogeneratton system of heat and power and power-gas cogeneration system. In order to further fully and reasonably use the heat in doubleeffect absorption units, double-stage bubble pump must be involved in the adoption o u pump replacing the traditional mechanical solution pump. It was designed a secon generator based on a solar pump-free lithium bromide absorption chiller system. The expenmen adopts the lunate thermosiphon elevation tube, ef...
Heat pumping in nanomechanical systems.

Science.gov (United States)

Chamon, Claudio; Mucciolo, Eduardo R; Arrachea, Liliana; Capaz, Rodrigo B

2011-04-01

We propose using a phonon pumping mechanism to transfer heat from a cold to a hot body using a propagating modulation of the medium connecting the two bodies. This phonon pump can cool nanomechanical systems without the need for active feedback. We compute the lowest temperature that this refrigerator can achieve. © 2011 American Physical Society
Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Directory of Open Access Journals (Sweden)

Imad M Tleyjeh

Full Text Available INTRODUCTION: Emerging epidemiological evidence suggests that proton pump inhibitor (PPI acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI. METHODS: Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. RESULTS: We identified 47 eligible citations (37 case-control and 14 cohort studies with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85, I(2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26-1.83. In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. CONCLUSIONS: In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class for an association between PPI use and CDI that does not support a cause-effect relationship.
Impact of gastro-oesophageal reflux disease on work productivity despite therapy with proton pump inhibitors in Germany

Directory of Open Access Journals (Sweden)

Gross M

2010-03-01

Full Text Available Abstract Background Gastro-oesophageal reflux disease (GERD is a common disorder with consequences for the patient's health-related quality of life (HRQoL. In Germany, few data are available on the impact of GERD on work-related productivity. Aim To study the impact of GERD on work productivity despite proton pump inhibitor (PPI therapy and the association between productivity and symptom duration, severity, and HRQoL. Methods Retrospective data from randomly selected patients with chronic GERD symptoms, treated by office-based general practitioners or general internists with routine clinical care, were analyzed together with information from self-administered instruments assessing work productivity (WPAI-GERD, symptoms (RDQ, and HRQoL (QOLRAD. Results Reduced productivity was reported by 152 of 249 patients (61.0%, although 89.5% of them were treated with PPI. The reduction in work productivity was 18.5% in all patients and 30.3% in those with reduced productivity. Patients with impaired productivity showed a significantly lower HRQoL and more-severe symptoms of reflux disease. In all patients, the mean sick leave attributable to reflux symptoms was 0.6 hours in the previous seven days and 1.4 work days in the previous three months. Conclusion GERD has a substantial impact on work productivity in Germany, even in patients receiving routine clinical care and PPI therapy.
TFCX pumped limiter and vacuum pumping system design and analysis

International Nuclear Information System (INIS)

Haines, J.R.

1985-04-01

Impurity control system design and performance studies were performed in support of the Tokamak Fusion Core Experiment (TFCX) pre-conceptual design. Efforts concentrated on pumped limiter and vacuum pumping system design configuration, thermal/mechanical and erosion lifetime performance of the limiter protective surface, and helium ash removal performance. The reference limiter design forms a continuous toroidal belt at the bottom of the device and features a flat surface with a single leading edge. The vacuum pumping system features large vacuum ducts (diameter approximately 1 m) and high-speed, compound cryopumps. Analysis results indicate that the limiter/vacuum pumping system design provides adequate helium ash removal. Erosion, primarily by disruption-induced vaporization and/or melting, limits the protective surface lifetime to about one calendar year or only about 60 full-power hours of operation. In addition to evaluating impurity control system performance for nominal TFCX conditions, these studies attempt to focus on the key plasma physics and engineering design issues that should be addressed in future research and development programs
Investigation into the Effects of the Variable Displacement Mechanism on Swash Plate Oscillation in High-Speed Piston Pumps

Directory of Open Access Journals (Sweden)

Xu Fang

2018-04-01

Full Text Available High-speed, pressure-compensated variable displacement piston pumps are widely used in aircraft hydraulic systems for their high power density. The swash plate is controlled by the pressure-compensated valve, which uses pressure feedback so that the instantaneous output flow of the pump is exactly enough to maintain a presetting pressure. The oscillation of the swash plate is one of the major excitation sources in the high-speed piston pump, which may cause lower efficiency, shorter service life, and even serious damage. This paper presents an improved model to investigate the influence of the variable displacement mechanism on the swash plate oscillation and introduces some feasible ways to reduce oscillation of the swash plate. Most of the variable structural parameters of the variable displacement mechanism are taken into consideration, and their influences on swash plate oscillation are discussed in detail. The influence of the load pipe on the oscillation of the swash plate is considered in the improved model. A test rig is built and similarities between the experiments and simulated results prove that the simulation model can effectively predict the variable displacement mechanism state. The simulation results show that increasing the volume of the outlet chamber, the spring stiffness of the control valve, the action area of the actuator piston, and offset distance of the actuator piston can significantly reduce the oscillation amplitude of the swash plate. Furthermore, reducing the diameter of the control valve spool and the dead volume of the actuator piston chamber can also have a positive effect on oscillation amplitude reduction.
Conserved phosphoryl transfer mechanisms within kinase families and the role of the C8 proton of ATP in the activation of phosphoryl transfer

Directory of Open Access Journals (Sweden)

Kenyon Colin P

2012-03-01

Full Text Available Abstract Background The kinome is made up of a large number of functionally diverse enzymes, with the classification indicating very little about the extent of the conserved kinetic mechanisms associated with phosphoryl transfer. It has been demonstrated that C8-H of ATP plays a critical role in the activity of a range of kinase and synthetase enzymes. Results A number of conserved mechanisms within the prescribed kinase fold families have been identified directly utilizing the C8-H of ATP in the initiation of phosphoryl transfer. These mechanisms are based on structurally conserved amino acid residues that are within hydrogen bonding distance of a co-crystallized nucleotide. On the basis of these conserved mechanisms, the role of the nucleotide C8-H in initiating the formation of a pentavalent intermediate between the γ-phosphate of the ATP and the substrate nucleophile is defined. All reactions can be clustered into two mechanisms by which the C8-H is induced to be labile via the coordination of a backbone carbonyl to C6-NH2 of the adenyl moiety, namely a "push" mechanism, and a "pull" mechanism, based on the protonation of N7. Associated with the "push" mechanism and "pull" mechanisms are a series of proton transfer cascades, initiated from C8-H, via the tri-phosphate backbone, culminating in the formation of the pentavalent transition state between the γ-phosphate of the ATP and the substrate nucleophile. Conclusions The "push" mechanism and a "pull" mechanism are responsible for inducing the C8-H of adenyl moiety to become more labile. These mechanisms and the associated proton transfer cascades achieve the proton transfer via different family-specific conserved sets of amino acids. Each of these mechanisms would allow for the regulation of the rate of formation of the pentavalent intermediate between the ATP and the substrate nucleophile. Phosphoryl transfer within kinases is therefore a specific event mediated and regulated via the
Metabolic Compensation of Fitness Costs Is a General Outcome for Antibiotic-Resistant Pseudomonas aeruginosa Mutants Overexpressing Efflux Pumps.

Science.gov (United States)

Olivares Pacheco, Jorge; Alvarez-Ortega, Carolina; Alcalde Rico, Manuel; Martínez, José Luis

2017-07-25

It is generally assumed that the acquisition of antibiotic resistance is associated with a fitness cost. We have shown that overexpression of the MexEF-OprN efflux pump does not decrease the fitness of a resistant Pseudomonas aeruginosa strain compared to its wild-type counterpart. This lack of fitness cost was associated with a metabolic rewiring that includes increased expression of the anaerobic nitrate respiratory chain when cells are growing under fully aerobic conditions. It was not clear whether this metabolic compensation was exclusive to strains overexpressing MexEF-OprN or if it extended to other resistant strains that overexpress similar systems. To answer this question, we studied a set of P. aeruginosa mutants that independently overexpress the MexAB-OprM, MexCD-OprJ, or MexXY efflux pumps. We observed increased expression of the anaerobic nitrate respiratory chain in all cases, with a concomitant increase in NO 3 consumption and NO production. These efflux pumps are proton/substrate antiporters, and their overexpression may lead to intracellular H + accumulation, which may in turn offset the pH homeostasis. Indeed, all studied mutants showed a decrease in intracellular pH under anaerobic conditions. The fastest way to eliminate the excess of protons is by increasing oxygen consumption, a feature also displayed by all analyzed mutants. Taken together, our results support metabolic rewiring as a general mechanism to avoid the fitness costs derived from overexpression of P. aeruginosa multidrug efflux pumps. The development of drugs that block this metabolic "reaccommodation" might help in reducing the persistence and spread of antibiotic resistance elements among bacterial populations. IMPORTANCE It is widely accepted that the acquisition of resistance confers a fitness cost in such a way that in the absence of antibiotics, resistant populations will be outcompeted by susceptible ones. Based on this assumption, antibiotic cycling regimes have been
Ion pump as Brownian motor: theory of electroconformational coupling and proof of ratchet mechanism for Na,K-ATPase action

Science.gov (United States)

Tsong, Tian Yow; Chang, Cheng-Hung

2003-04-01

This article reviews some concepts of the Brownian Ratchet which are relevant to our discussion of mechanisms of action of Na,K-ATPase, a universal ion pump and an elemental motor protein of the biological cell. Under wide ranges of ionic compositions it can hydrolyze an ATP and use the γ-phosphorous bond energy of ATP to pump 3 Na + out of, and 2 K + into the cell, both being uphill transport. During the ATP-dependent pump cycle, the enzyme oscillates between E1 and E2 states. Our experiment replaces ATP with externally applied electric field of various waveforms, amplitudes, and frequencies. The field enforced-oscillation, or fluctuation of E1 and E2 states enables the enzyme to harvest energy from the applied field and convert it to the chemical gradient energy of cations. A theory of electroconformational coupling (TEC), which embodies all the essential features of the Brownian Ratchet, successfully simulates these experimental results. Our analysis based on a four-state TEC model indicates that the equilibrium and the rate constants of the transport system define the frequency and the amplitude of the field for the optimal activation. Waveform, frequency, and amplitude are three elements of signal. Thus, electric signal of the ion pump is found by TEC analysis of the experimental data. Electric noise (white) superimposed on an electric signal changes the pump efficiency and produces effects similar to the stochastic resonance reported in other biological systems. The TEC concept is compared with the most commonly used Michaelis-Menten enzyme mechanism (MME) for similarities and differences. Both MME and TEC are catalytic wheels, which recycle the catalyst in each turnover. However, a MME can only catalyze reaction of descending free energy while a TEC enzyme can catalyze reaction of ascending free energy by harvesting needed energy from an off-equilibrium electric noise. The TEC mechanism is shown to be applicable to other biological motors and engines, as

Centrifugal Force Based Magnetic Micro-Pump Driven by Rotating Magnetic Fields

International Nuclear Information System (INIS)

Kim, S H; Hashi, S; Ishiyama, K

2011-01-01

This paper presents a centrifugal force based magnetic micro-pump for the pumping of blood. Most blood pumps are driven by an electrical motor with wired control. To develop a wireless and battery-free blood pump, the proposed pump is controlled by external rotating magnetic fields with a synchronized impeller. Synchronization occurs because the rotor is divided into multi-stage impeller parts and NdFeB permanent magnet. Finally, liquid is discharged by the centrifugal force of multi-stage impeller. The proposed pump length is 30 mm long and 19 mm in diameter which much smaller than currently pumps; however, its pumping ability satisfies the requirement for a blood pump. The maximum pressure is 120 mmHg and the maximum flow rate is 5000ml/min at 100 Hz. The advantage of the proposed pump is that the general mechanical problems of a normal blood pump are eliminated by the proposed driving mechanism.
Centrifugal Force Based Magnetic Micro-Pump Driven by Rotating Magnetic Fields

Science.gov (United States)

Kim, S. H.; Hashi, S.; Ishiyama, K.

2011-01-01

This paper presents a centrifugal force based magnetic micro-pump for the pumping of blood. Most blood pumps are driven by an electrical motor with wired control. To develop a wireless and battery-free blood pump, the proposed pump is controlled by external rotating magnetic fields with a synchronized impeller. Synchronization occurs because the rotor is divided into multi-stage impeller parts and NdFeB permanent magnet. Finally, liquid is discharged by the centrifugal force of multi-stage impeller. The proposed pump length is 30 mm long and19 mm in diameter which much smaller than currently pumps; however, its pumping ability satisfies the requirement for a blood pump. The maximum pressure is 120 mmHg and the maximum flow rate is 5000ml/min at 100 Hz. The advantage of the proposed pump is that the general mechanical problems of a normal blood pump are eliminated by the proposed driving mechanism.
Two proton decay in 12O

International Nuclear Information System (INIS)

Kumawat, M.; Singh, U.K.; Jain, S.K.; Saxena, G.; Kaushik, M.; Aggarwal, Mamta

2017-01-01

Two-proton radioactivity was observed experimentally in the decay of 45 Fe, 54 Zn and 48 Ni. From then many theoretical studies of one and two-proton radioactivity have been carried out within the framework of different models including RMF+BCS approach for medium mass region. Towards light mass region proton-proton correlations were observed in two-proton decay of 19 Mg and 16 Ne. Recently, different mechanism of two-proton emission from proton-rich nuclei 23 Al and 22 Mg has been investigated and transition from direct to sequential two-proton decay in sd shell nuclei is observed. Encouraged with these recent studies of two proton emission in light mass nuclei, we have applied our RMF+BCS approach for the study of two proton emission in light mass region and in this paper we present our result of two proton emission in 12 O
Proton pump inhibitor step-down therapy for GERD: A multi-center study in Japan

Science.gov (United States)

Tsuzuki, Takao; Okada, Hiroyuki; Kawahara, Yoshiro; Takenaka, Ryuta; Nasu, Junichiro; Ishioka, Hidehiko; Fujiwara, Akiko; Yoshinaga, Fumiya; Yamamoto, Kazuhide

2011-01-01

AIM: To investigate the predictors of success in step-down of proton pump inhibitor and to assess the quality of life (QOL). METHODS: Patients who had heartburn twice a week or more were treated with 20 mg omeprazole (OPZ) once daily for 8 wk as an initial therapy (study 1). Patients whose heartburn decreased to once a week or less at the end of the initial therapy were enrolled in study 2 and treated with 10 mg OPZ as maintenance therapy for an additional 6 mo (study 2). QOL was investigated using the gastrointestinal symptom rating scale (GSRS) before initial therapy, after both 4 and 8 wk of initial therapy, and at 1, 2, 3, and 6 mo after starting maintenance therapy. RESULTS: In study 1, 108 patients were analyzed. Their characteristics were as follows; median age: 63 (range: 20-88) years, sex: 46 women and 62 men. The success rate of the initial therapy was 76%. In the patients with successful initial therapy, abdominal pain, indigestion and reflux GSRS scores were improved. In study 2, 83 patients were analyzed. Seventy of 83 patients completed the study 2 protocol. In the per-protocol analysis, 80% of 70 patients were successful for step-down. On multivariate analysis of baseline demographic data and clinical information, no previous treatment for gastroesophageal reflux disease (GERD) [odds ratio (OR) 0.255, 95% CI: 0.06-0.98] and a lower indigestion score in GSRS at the beginning of step-down therapy (OR 0.214, 95% CI: 0.06-0.73) were found to be the predictors of successful step-down therapy. The improved GSRS scores by initial therapy were maintained through the step-down therapy. CONCLUSION: OPZ was effective for most GERD patients. However, those who have had previous treatment for GERD and experience dyspepsia before step-down require particular monitoring for relapse. PMID:21472108
The proton pump inhibitor lansoprazole improves the skeletal phenotype in dystrophin deficient mdx mice.

Directory of Open Access Journals (Sweden)

Arpana Sali

Full Text Available In Duchenne muscular dystrophy (DMD, loss of the membrane stabilizing protein dystrophin results in myofiber damage. Microinjury to dystrophic myofibers also causes secondary imbalances in sarcolemmic ion permeability and resting membrane potential, which modifies excitation-contraction coupling and increases proinflammatory/apoptotic signaling cascades. Although glucocorticoids remain the standard of care for the treatment of DMD, there is a need to investigate the efficacy of other pharmacological agents targeting the involvement of imbalances in ion flux on dystrophic pathology.We designed a preclinical trial to investigate the effects of lansoprazole (LANZO administration, a proton pump inhibitor, on the dystrophic muscle phenotype in dystrophin deficient (mdx mice. Eight to ten week-old female mice were assigned to one of four treatment groups (n = 12 per group: (1 vehicle control; (2 5 mg/kg/day LANZO; (3 5 mg/kg/day prednisolone; and (4 combined treatment of 5 mg/kg/day prednisolone (PRED and 5 mg/kg/day LANZO. Treatment was administered orally 5 d/wk for 3 months. At the end of the study, behavioral (Digiscan and functional outcomes (grip strength and Rotarod were assessed prior to sacrifice. After sacrifice, body, tissue and organ masses, muscle histology, in vitro muscle force, and creatine kinase levels were measured. Mice in the combined treatment groups displayed significant reductions in the number of degenerating muscle fibers and number of inflammatory foci per muscle field relative to vehicle control. Additionally, mice in the combined treatment group displayed less of a decline in normalized forelimb and hindlimb grip strength and declines in in vitro EDL force after repeated eccentric contractions.Together our findings suggest that combined treatment of LANZO and prednisolone attenuates some components of dystrophic pathology in mdx mice. Our findings warrant future investigation of the clinical efficacy of LANZO and
Solar and wind potentialities in Mauritania. Presentation of pumping

International Nuclear Information System (INIS)

Adell, A.; Fagel, L.

1996-01-01

The programs of rural hydraulics based upon the use of renewable energies, either solar or wind, have gained in importance in Africa during the last decade; particularly in Mauritania, a Sahelian country, which is extending widely beyond the western edge of Sahara. This country has been hardly affected by the prolonged droughts which have recently struck this region. Water is a major problem here. Important projects appeared concerning the pumping of water with the help of solar photovoltaic systems and wind mechanical pumps; other processes are being studied: pumping with aero-generators, sea water desalinating... Today Mauritania is at the top of countries of the subregion concerning the number of installations of wind mechanical pumps. The meteorological conditions are in fact favourable to such realizations. A technical and economic comparative study of the results of functioning obtained on the field with a photovoltaic pumping installation and a wind pumping installation, is presented: better technical performances and greater reliability for the photovoltaic pump, lower cost and technological mastery for the wind pump. (author). 9 refs., 8 figs
Demonstration of the reliability of the safety pumps

International Nuclear Information System (INIS)

Durand, J.M.

1989-01-01

POMPES GUINARD is supplying about 60% of the Nuclear pumps for the French Program. To become the specialist of Safety Related Pumps POMPES GUINARD made a lot of efforts and investments to acquire knowledge and experience. This was possible mainly with test on special loops as it is the only way for a pump manufacturer to progress by controlling hydraulics, components, bearings, mechanical seals, inducer, mechanical and hydraulic behaviour of the units in process of time. We will describe hereafter some of the typical tests which were performed during the last fifteen years
V-ATPase-mediated granular acidification is regulated by the V-ATPase accessory subunit Ac45 in POMC-producing cells.

NARCIS (Netherlands)

Jansen, E.J.S.; Hafmans, T.G.M.; Martens, G.J.

2010-01-01

The vacuolar (H(+))-ATPase (V-ATPase) is an important proton pump, and multiple critical cell-biological processes depend on the proton gradient provided by the pump. Yet, the mechanism underlying the control of the V-ATPase is still elusive but has been hypothesized to involve an accessory subunit
The Causes and Prevention Measures of Stuck Pump Phenomenon of Rod-pumped Well in CBM Field

Science.gov (United States)

Yonggui, Mei

2018-02-01

In the process of CBM field exploitation, in order to realize the drainage equipment to work continuous stably, the article pays attention to study and solve the stuck pump problem, and aim of reducing reservoir damage and lowing production costs. Through coal particles stuck pump experiment and sediment composition analysis, we find out five primary cause of stuck pump phenomenon: sand from coal seam, sediment from ground, iron corrosion, iron scrap caused by eccentric wear, coal cake. According to stuck pump mechanism, the article puts forward 8 measures to prevent stuck pump phenomenon, and the measures are focused on technology optimization, operation management and drainage process control. After 7 years production practice, the yearly stuck pump rate has dropped from 8.9% to 1.2%, and the pump inspection period has prolonged 2 times. The experiment result shows that pure coal particles cannot cause stuck pump, but sand, scrap iron, and iron corrosion are the primary cause of stuck pump. The article study and design the new pipe string structure that the bottom of the pipe string is open. This kind of pipe string applied the sedimentation terminal velocity theory to solve the stuck pump phenomenon, and it can be widely used in CBM drainage development.
Thermodynamic performance of multi-stage gradational lead screw vacuum pump

Science.gov (United States)

Zhao, Fan; Zhang, Shiwei; Sun, Kun; Zhang, Zhijun

2018-02-01

As a kind of dry mechanical vacuum pump, the twin-screw vacuum pump has an outstanding pumping performance during operation, widely used in the semiconductor industry. Compared with the constant lead screw (CLS) vacuum pump, the gradational lead screw (GLS) vacuum pump is more popularly applied in recent years. Nevertheless, not many comparative studies on the thermodynamic performance of GLS vacuum pump can be found in the literature. Our study focuses on one type of GLS vacuum pump, the multi-stage gradational lead screw (MGLS) vacuum pump, gives a detailed description of its construction and illustrates it with the drawing. Based on the structural analysis, the thermodynamic procedure is divided into four distinctive processes, including sucking process, transferring (compressing) process, backlashing process and exhausting process. The internal mechanism of each process is qualitatively illustrated and the mathematical expressions of seven thermodynamic parameters are given under the ideal situation. The performance curves of MGLS vacuum pump are plotted by MATLAB software and compared with those of the CLS vacuum pump in the same case. The results can well explain why the MGLS vacuum pump has more favorable pumping performance than the CLS vacuum pump in saving energy, reducing noise and heat dissipation.
Stereochemistry-Dependent Proton Conduction in Proton Exchange Membrane Fuel Cells.

Science.gov (United States)

Thimmappa, Ravikumar; Devendrachari, Mruthyunjayachari Chattanahalli; Kottaichamy, Alagar Raja; Tiwari, Omshanker; Gaikwad, Pramod; Paswan, Bhuneshwar; Thotiyl, Musthafa Ottakam

2016-01-12

Graphene oxide (GO) is impermeable to H2 and O2 fuels while permitting H(+) shuttling, making it a potential candidate for proton exchange membrane fuel cells (PEMFC), albeit with a large anisotropy in their proton transport having a dominant in plane (σIP) contribution over the through plane (σTP). If GO-based membranes are ever to succeed in PEMFC, it inevitably should have a dominant through-plane proton shuttling capability (σTP), as it is the direction in which proton gets transported in a real fuel-cell configuration. Here we show that anisotropy in proton conduction in GO-based fuel cell membranes can be brought down by selectively tuning the geometric arrangement of functional groups around the dopant molecules. The results show that cis isomer causes a selective amplification of through-plane proton transport, σTP, pointing to a very strong geometry angle in ionic conduction. Intercalation of cis isomer causes significant expansion of GO (001) planes involved in σTP transport due to their mutual H-bonding interaction and efficient bridging of individual GO planes, bringing down the activation energy required for σTP, suggesting the dominance of a Grotthuss-type mechanism. This isomer-governed amplification of through-plane proton shuttling resulted in the overall boosting of fuel-cell performance, and it underlines that geometrical factors should be given prime consideration while selecting dopant molecules for bringing down the anisotropy in proton conduction and enhancing the fuel-cell performance in GO-based PEMFC.
Evaluation of a Proton Pump Inhibitor for Sleep Bruxism: A Randomized Clinical Trial.

Science.gov (United States)

Ohmure, H; Kanematsu-Hashimoto, K; Nagayama, K; Taguchi, H; Ido, A; Tominaga, K; Arakawa, T; Miyawaki, S

2016-12-01

Bruxism is a repetitive jaw-muscle activity characterized by clenching or grinding of the teeth and/or bracing or thrusting of the mandible. Recent advances have clarified the relationship between gastroesophageal reflux and sleep bruxism (SB). However, the influence of pharmacological elimination of gastric acid secretion on SB has not been confirmed. The authors aimed to assess the efficacy of a proton pump inhibitor (PPI) on SB and to examine the gastrointestinal (GI) symptoms and endoscopic findings of the upper GI tract in SB patients. The authors performed a randomized double-blind placebo-controlled crossover study at Kagoshima University Hospital. Twelve patients with polysomnography (PSG)-diagnosed SB underwent an assessment of GI symptoms using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) and esophagogastroduodenoscopy. At baseline (i.e., before interventions), the mean frequencies of electromyography (EMG) bursts and rhythmic masticatory muscle activity (RMMA) episodes were 65.4 ± 49.0 bursts/h and 7.0 ± 4.8 episodes/h, respectively, and at least 1 RMMA episode with grinding noise was confirmed in all participants. The mean FSSG score was 8.4 ± 5.6, and 41.7% of patients were diagnosed with gastroesophageal reflux disease. Mild reflux esophagitis was confirmed in 6 patients. PSG, including EMG of the left masseter muscle and audio-video recording, was performed on days 4 and 5 of administration of 10 mg of the PPI (rabeprazole) or placebo. PPI administration yielded a significant reduction in the frequency of EMG bursts, RMMA episodes, and grinding noise. No significant differences were observed regarding the swallowing events and sleep variables. Since the clinical application of PPI for SB treatment should remain on hold at present, the results of this trial highlight the potential application of pharmacological gastroesophageal reflux disease treatment for SB patients. Larger scale studies are warranted to
Multicavity proton cyclotron accelerator

Directory of Open Access Journals (Sweden)

J. L. Hirshfield

2002-08-01

Full Text Available A mechanism for acceleration of protons is described, in which energy gain occurs near cyclotron resonance as protons drift through a sequence of rotating-mode TE_{111} cylindrical cavities in a strong nearly uniform axial magnetic field. Cavity resonance frequencies decrease in sequence from one another with a fixed frequency interval Δf between cavities, so that synchronism can be maintained between the rf fields and proton bunches injected at intervals of 1/Δf. An example is presented in which a 122 mA, 1 MeV proton beam is accelerated to 961 MeV using a cascade of eight cavities in an 8.1 T magnetic field, with the first cavity resonant at 120 MHz and with Δf=8 MHz. Average acceleration gradient exceeds 40 MV/m, average effective shunt impedance is 223 MΩ/m, but maximum surface field in the cavities does not exceed 7.2 MV/m. These features occur because protons make many orbital turns in each cavity and thus experience acceleration from each cavity field many times. Longitudinal and transverse stability appear to be intrinsic properties of the acceleration mechanism, and an example to illustrate this is presented. This acceleration concept could be developed into a proton accelerator for a high-power neutron spallation source, such as that required for transmutation of nuclear waste or driving a subcritical fission burner, provided a number of significant practical issues can be addressed.
Root bacterial endophytes confer drought resistance and enhance expression and activity of a vacuolar H+ -pumping pyrophosphatase in pepper plants.

Science.gov (United States)

Vigani, Gianpiero; Rolli, Eleonora; Marasco, Ramona; Dell'Orto, Marta; Michoud, Grégoire; Soussi, Asma; Raddadi, Noura; Borin, Sara; Sorlini, Claudia; Zocchi, Graziano; Daffonchio, Daniele

2018-05-22

It has been previously shown that the transgenic overexpression of the plant root vacuolar proton pumps H + -ATPase (V-ATPase) and H + -PPase (V-PPase) confer tolerance to drought. Since plant-root endophytic bacteria can also promote drought tolerance, we hypothesize that such promotion can be associated to the enhancement of the host vacuolar proton pumps expression and activity. To test this hypothesis, we selected two endophytic bacteria endowed with an array of in vitro plant growth promoting traits. Their genome sequences confirmed the presence of traits previously shown to confer drought resistance to plants, such as the synthesis of nitric oxide and of organic volatile organic compounds. We used the two strains on pepper (Capsicuum annuum L.) because of its high sensitivity to drought. Under drought conditions, both strains stimulated a larger root system and enhanced the leaves' photosynthetic activity. By testing the expression and activity of the vacuolar proton pumps, H + -ATPase (V-ATPase) and H + -PPase (V-PPase), we found that bacterial colonization enhanced V-PPase only. We conclude that the enhanced expression and activity of V-PPase can be favoured by the colonization of drought-tolerance-inducing bacterial endophytes. This article is protected by copyright. All rights reserved. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.
EXPERIMENTAL AND COMPUTATIONAL STUDIES OF THE FORMATION MECHANISM OF PROTONATED INTERSTELLAR DIAZINES

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhe-Chen; Cole, Callie A.; Bierbaum, Veronica M. [Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 (United States); Snow, Theodore P., E-mail: zhwa4666@colorado.edu [Department of Astrophysical and Planetary Sciences, University of Colorado, Boulder, CO 80309 (United States)

2015-01-10

Studies of interstellar chemistry have grown in number and complexity by both observations and laboratory measurements, and nitrogen-containing aromatics have been implicated as important interstellar molecules. In this paper, the gas-phase collision induced dissociation (CID) processes of protonated pyridazine (1,2-diazine), pyrimidine (1,3-diazine), and pyrazine (1,4-diazine) cations (C{sub 4}H{sub 5}N{sub 2} {sup +}) are investigated in detail both experimentally and theoretically. The major neutral loss for all three CID processes is HCN, leading to the formation of C{sub 3}H{sub 4}N{sup +} isomers; our density functional theory (DFT) calculations support and elucidate our experimental results. The formation of C{sub 3}H{sub 4}N{sup +} isomers from the reaction of abundant interstellar acrylonitrile (CH{sub 2}CHCN) and H{sup +}is also studied employing DFT calculations. Our results lead to a novel mechanism for interstellar protonated diazine formation from the consecutive reactions of CH{sub 2}CHCN+ H{sup +} + HCN. Moreover, our results motivate the continuing search for interstellar C{sub 3}H{sub 4}N{sup +} isomers as well as polycyclic aromatic N-containing hydrocarbons (PANHs)
Mechanism of collective interaction in disintegration of heavy nuclei by protons with the energy of 1 GeV

International Nuclear Information System (INIS)

Birbrair, B.L.; Gridnev, A.B.; Il'in, A.I.

1984-01-01

A two-shoulder time-of-flight spectrometer has been used to investigate deep inelastic disintegration of heavy nuclei by 1 GeV protons. Masses, kinetic energies and momenta of two additional massive fragments dispersing perpendicularly to a primary proton beam were measured in the experiment. Events with essential nucleon losses (up to 100 a.u.m.) are stated to be characterized by increased total kinetic energy of fragments and noticeable value of transferred and transverse momenta as well (up to 2-3 GeV/c). These kinematic peculiarities testify to presence of a special mechanism of heavy nucleus disintegration followed by essential nucleon losses. The threshold value of nucleon losses (45+-5) a.u.m. corresponding to transition from ordinary high-energy pressure after intranuclear cascade to a new mechanism of nuclear reaction is determined. The main peculiarity of the new mechanism is that a group of nucleons receiving essential part of energy and momentum of an incident particle is separated inside the nucleus. The physical reason for this collective mechanism of interaction can be associated with production of pion bubbles inside the nucleus under pion interaction with a nucleus regarded as a relativistic nucleon system
21 CFR 870.4370 - Roller-type cardiopulmonary bypass blood pump.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Roller-type cardiopulmonary bypass blood pump. 870... Roller-type cardiopulmonary bypass blood pump. (a) Identification. A roller-type cardiopulmonary bypass blood pump is a device that uses a revolving roller mechanism to pump the blood through the...
Effect of the Shrink Fit and Mechanical Tolerance on Reactor Coolant Pump Flywheel Integrity Evaluation

Energy Technology Data Exchange (ETDEWEB)

Kim, Donghak [Korea KHNP Central Research Institute, Daejeon (Korea, Republic of)

2015-10-15

Reactor coolant pump (RCP) flywheel should satisfy the RCP flywheel integrity criteria of the US NRC standard review plan (SRP) 5.4.1.1 and regulatory guide (RG) 1.14. Shrink-fit and rotational stresses should be calculated to evaluate the integrity. In this paper the effects of the shrink fit and mechanical tolerance on the RCP flywheel integrity evaluation are studied. The shrink fit should be determined by the joint release speed and the stresses in the flywheel will be increased by the shrink fit. The stress at the interface between the hub and the outer wheel shows the highest value. The effect of the mechanical tolerance should be considered for the stress evaluation. And the effect of the mechanical tolerance should be not considered to determine the joint release speed.
Effect of the Shrink Fit and Mechanical Tolerance on Reactor Coolant Pump Flywheel Integrity Evaluation

International Nuclear Information System (INIS)

Kim, Donghak

2015-01-01

Reactor coolant pump (RCP) flywheel should satisfy the RCP flywheel integrity criteria of the US NRC standard review plan (SRP) 5.4.1.1 and regulatory guide (RG) 1.14. Shrink-fit and rotational stresses should be calculated to evaluate the integrity. In this paper the effects of the shrink fit and mechanical tolerance on the RCP flywheel integrity evaluation are studied. The shrink fit should be determined by the joint release speed and the stresses in the flywheel will be increased by the shrink fit. The stress at the interface between the hub and the outer wheel shows the highest value. The effect of the mechanical tolerance should be considered for the stress evaluation. And the effect of the mechanical tolerance should be not considered to determine the joint release speed
PSY

DEFF Research Database (Denmark)

Kristensen, Astrid

Plant must adapt to changing environmental factors and coordinate their growth and development accordingly. This is accomplished with effective cell communication that includes signaling molecules and receptors to perceive the signal. Plasma membrane proton pumps are key plant proteins...... activation of the pump. Plants exposed to exogenously applied PSY1 showed an increased level of phosphorylated T881 as well as rapid proton efflux from roots. The physiological effect of this proton pump activation was demonstrated to initiate cell elongation. The activation mechanism of PSY1R involved...

An experimental investigation of pump as turbine for micro hydro application

International Nuclear Information System (INIS)

Raman, N; Hussein, I; Palanisamy, K; Foo, B

2013-01-01

This paper presents the results of an experimental investigation of a centrifugal pump working as turbine (PAT). An end suction centrifugal pump was tested in turbine mode at PAT experimental rig installed in the Mechanical Engineering Laboratory of Universiti Tenaga Nasional. The pump with specific speed of 15.36 (m, m 3 /s) was used in the experiment and the performance characteristic of the PAT was determined. The experiment showed that a centrifugal pump can satisfactorily be operated as turbine without any mechanical problems. As compared to pump operation, the pump was found to operate at higher heads and discharge values in turbine mode. The best efficiency point (BEP) in turbine mode was found to be lower than BEP in pump mode. The results obtained were also compared to the work of some previous researchers.
Residual heat removal pump retrofit program

International Nuclear Information System (INIS)

Dudiak, J.G.; McKenna, J.M.

1990-01-01

Residual Heat Removal (RHR) pumps installed in pressurized water reactor power plants are used to provide the removal of decay heat from the reactor and to provide low head safety injection in the event of loss of coolant in the reactor coolant system. These pumps are subjected to rather severe temperature and pressure transients, therefore, the majority of pumps installed in the RHR service are vertical pumps with a single stage impeller. RHR pumps have traditionally been a significant maintenance item for many utilities. The close-coupled pump design requires disassembly of the casing cover from the lower pump casing while performing these routine maintenance tasks. The casing separation requires the loosening of numerous highly torqued studs. Once the casing is separated, the impeller is dropped from the motor shaft to allow removal of the mechanical seal and casing cover from the motor shaft. Galling of the impeller to the motor shaft is not uncommon. The RHR pump internals are radioactive and the separation of the pump casing to perform routine maintenance exposes the maintenance personnel to high radiation levels. The handling of the impeller also exposes the maintenance personnel to high radiation levels. This paper introduces a design modification developed to convert the close-coupled RHR pumps to a coupled configuration
ZmPUMP encodes a fully functional monocot plant uncoupling mitochondrial protein whose affinity to fatty acid is increased with the introduction of a His pair at the second matrix loop

International Nuclear Information System (INIS)

Favaro, Regiane Degan; Borecky, Jiri; Colombi, Debora; Maia, Ivan G.

2006-01-01

Uncoupling proteins (UCPs) are specialized mitochondrial transporter proteins that uncouple respiration from ATP synthesis. In this study, cDNA encoding maize uncoupling protein (ZmPUMP) was expressed in Escherichia coli and recombinant ZmPUMP reconstituted in liposomes. ZmPUMP activity was associated with a linoleic acid (LA)-mediated H + efflux with K m of 56.36 ± 0.27 μM and V max of 66.9 μmol H + min -1 (mg prot) -1 . LA-mediated H + fluxes were sensitive to ATP inhibition with K i of 2.61 ± 0.36 mM (at pH 7.2), a value similar to those for dicot UCPs. ZmPUMP was also used to investigate the importance of a histidine pair present in the second matrix loop of mammalian UCP1 and absent in plant UCPs. ZmPUMP with introduced His pair (Lys155His and Ala157His) displayed a 1.55-fold increase in LA-affinity while its activity remained unchanged. Our data indicate conserved properties of plant UCPs and suggest an enhancing but not essential role of the histidine pair in proton transport mechanism
Emergency recirculation pump driving mechanism

International Nuclear Information System (INIS)

Morooka, Shin-ichi.

1980-01-01

Purpose: To sufficiently secure the coolant flow rate in a reactor core and restrict the temperature on the surface of fuel elements to low degree when the coolant is lost in a BWR type reactor. Constitution: In order to secure sufficient coolant flow rate in a reactor core and to sufficiently cool the reactor core when the coolant is lost in a BWR type reactor, it is tripped upon loss of power supply simultaneously when an accident occurs, a recycling pump at the side of normal reactor where its rotating speed is decelerated in accordance with its inertia is restarted by the pressure water stored in a tank out of the reactor to increase the coolant flow rate in the reactor core so as to sufficiently cool the reactor core. (Aizawa, K.)
Variable load failure mechanism for high-speed load sensing electro-hydrostatic actuator pump of aircraft

Directory of Open Access Journals (Sweden)

Cun SHI

2018-05-01

Full Text Available This paper presents a novel transient lubrication model for the analysis of the variable load failure mechanism of high-speed pump used in Load Sensing Electro-Hydrostatic Actuator (LS-EHA. Focusing on the slipper/swashplate pair partial abrasion, which is considered as the dominant failure mode in the high-speed condition, slipper dynamic models are established. A forth sliding motion of the slipper on the swashplate surface is presented under the fact that the slipper center of mass will rotate around the center of piston ball when the swashplate angle is dynamically adjusted. Besides, extra inertial tilting moments will be produced for the slipper based on the theorem on translation of force, which will increase rapidly when LS-EHA pump operates under high-speed condition. Then, a dynamic lubricating model coupling with fluid film thickness field, temperature field and pressure field is proposed. The deformation effects caused by thermal deflection and hydrostatic pressure are considered. A numerical simulation model is established to validate the effectiveness and accuracy of the proposed model. Finally, based on the load spectrum of aircraft flight profile, the variable load conditions and the oil film characteristics are analyzed, and series of variable load rules of oil film thickness with variable speed/variable pressure/variable displacement are concluded. Keywords: Coupling lubrication model, Electro-Hydrostatic Actuator (EHA, High-speed pump, Partial abrasion, Slipper pair, Variable load
Pumping behavior of sputter ion pumps

International Nuclear Information System (INIS)

Chou, T.S.; McCafferty, D.

The ultrahigh vacuum requirements of ISABELLE is obtained by distributed pumping stations. Each pumping station consists of 1000 l/s titanium sublimation pump for active gases (N 2 , H 2 , O 2 , CO, etc.), and a 20 l/s sputter ion pump for inert gases (methane, noble gases like He, etc.). The combination of the alarming production rate of methane from titanium sublimation pumps (TSP) and the decreasing pumping speed of sputter ion pumps (SIP) in the ultrahigh vacuum region (UHV) leads us to investigate this problem. In this paper, we first describe the essential physics and chemistry of the SIP in a very clean condition, followed by a discussion of our measuring techniques. Finally measured methane, argon and helium pumping speeds are presented for three different ion pumps in the range of 10 -6 to 10 -11 Torr. The virtues of the best pump are also discussed
Analysis, occurrence, fate and risks of proton pump inhibitors, their metabolites and transformation products in aquatic environment: A review.

Science.gov (United States)

Kosma, Christina I; Lambropoulou, Dimitra A; Albanis, Triantafyllos A

2016-11-01

Proton pump inhibitors (PPIs) which include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole, are extensively used for the relief of gastro-intestinal disorders. Despite their high worldwide consumption, PPIs are extensively metabolized in human bodies and therefore are not regularly detected in monitoring studies. Very recently, however, it has been shown that some omeprazole metabolites may enter and are likely to persist in aquatic environment. Hence, to fully assess the environmental exposures and risks associated with PPIs, it is important to better understand and evaluate the fate and behavior not only of the parent compound but also of their metabolites and their transformation products arising from biotic and abiotic processes (hydrolysis, photodegradation, biodegradation etc.) in the environment. In this light, the purpose of this review is to summarize the present state of knowledge on the introduction and behavior of these chemicals in natural and engineering systems and highlight research needs and gaps. It draws attention to their transformation, the increase contamination by their metabolites/TPs in different environmental matrices and their potential adverse effects in the environment. Furthermore, existing research on analytical developments with respect to sample treatment, separation and detection of PPIs and their metabolites/TPs is provided. Copyright © 2016 Elsevier B.V. All rights reserved.
Performance characteristics of a continuous-flow fluidic pump

International Nuclear Information System (INIS)

Robinson, S.M.; Counce, R.M.; Smith, G.V.

1987-01-01

The fluidic pump is a type of positive-displacement pump in which basic fluid mechanics phenomena are utilized to eliminate valves and other moving parts that are exposed to the fluid being transferred. The version described in this article is powered by gas pressure serving as gas pistons and is virtually maintenance-free. It utilizes two displacement vessels and is designed to produce a steady and continuous liquid flow. This type of pump may be very useful for the transfer of radioactive or hazardous liquids where mechanical maintenance may be difficult or exposure of personnel to the fluid is undesirable. This paper presents experimental and model-predicted characteristics of such systems. The effects of several geometric parameters and operating conditions on the performance of the pump are briefly discussed
85,000-GPM, single-stage, single-suction LMFBR intermediate centrifugal pump

International Nuclear Information System (INIS)

Fair, C.E.; Cook, M.E.; Huber, K.A.; Rohde, R.

1983-01-01

The mechanical and hydraulic design features of the 85,000-gpm, single-stage, single-suction pump test article, which is designed to circulate liquid-sodium coolant in the intermediate heat-transport system of a Large-Scale Liquid Metal Fast Breeder Reactor (LS-LMFBR), are described. The design and analytical considerations used to satisfy the pump performance and operability requirements are presented. The validation of pump hydraulic performance using a hydraulic scale-model pump is discussed, as is the featute test for the mechanical-shaft seal system
Experimental Study on Fracture Failure of BRW 250 Pump Liquid Valve Mechanical Spring Surface

Directory of Open Access Journals (Sweden)

Rui Zeng

2017-01-01

Full Text Available In this paper, the singularity analysis method based on the continuous wave for the vibration signal of the plunger pump liquid valve under different conditions was studied, and the LMS based weighted least square method with good robustness and validity was proposed to calculate the LPZ index, which was the judgment criterion for fault of liquid valve mechanical spring. Fault diagnostic test results showed that the method could overcome the singularity of the binary discrete wave in the detection and quantitative accuracy problem, realize the accurate positioning of the singular point in the signal, identify the liquid valve disc in the spring break state to the liquid valve seat or lift limit the impact of the moment, and determine the fault of the liquid valve mechanical spring effectively.
Azole resistance in Candida spp. isolated from Catú Lake, Ceará, Brazil: an efflux-pump-mediated mechanism

Directory of Open Access Journals (Sweden)

Raimunda S.N. Brilhante

2016-03-01

Full Text Available Abstract Since, there is no study reporting the mechanism of azole resistance among yeasts isolated from aquatic environments; the present study aims to investigate the occurrence of antifungal resistance among yeasts isolated from an aquatic environment, and assess the efflux-pump activity of the azole-resistant strains to better understand the mechanism of resistance for this group of drugs. For this purpose, monthly water and sediment samples were collected from Catú Lake, Ceará, Brazil, from March 2011 to February 2012. The obtained yeasts were identified based on morphological and biochemical characteristics. Of the 46 isolates, 37 were Candida spp., 4 were Trichosporon asahii, 3 were Cryptococcus laurentii, 1 Rhodotorula mucilaginosa, and 1 was Kodamaea ohmeri. These isolates were subjected to broth microdilution assay with amphotericin B, itraconazole, and fluconazole, according to the methodology standardized by the Clinical and Laboratory Standards Institute (CLSI. The minimum inhibitory concentrations (MICs of amphotericin B, itraconazole, and fluconazole were 0.03125–2 µg/mL, 0.0625 to ≥16 µg/mL, and 0.5 to ≥64 µg/mL, respectively, and 13 resistant azole-resistant Candida isolates were detected. A reduction in the azole MICs leading to the phenotypical reversal of the azole resistance was observed upon addition of efflux-pump inhibitors. These findings suggest that the azole resistance among environmental Candida spp. is most likely associated with the overexpression of efflux-pumps.
Electric heat-pumps in residential buildings

Energy Technology Data Exchange (ETDEWEB)

1983-03-01

Since the end of 1979 every other day an electrically operated heat-pump has started operation in Berlin (West). Pros and cons of heat-pumps are a much discussed subject. But what is the opinion of the user. As it is not known the BEWAG carried out a written customer inquiry in the summer 1982. The aim of the inquiry was to improve the advisory service by means of the answers obtained, to obtain information about the reliability or liability to defects of the heat pump, the mechanism they operate on and to know how big the oil substitution potential is. Customer satisfaction with the heat pumps was a further point of interest.
Alpha-helical hydrophobic polypeptides form proton-selective channels in lipid bilayers

Science.gov (United States)

Oliver, A. E.; Deamer, D. W.

1994-01-01

Proton translocation is important in membrane-mediated processes such as ATP-dependent proton pumps, ATP synthesis, bacteriorhodopsin, and cytochrome oxidase function. The fundamental mechanism, however, is poorly understood. To test the theoretical possibility that bundles of hydrophobic alpha-helices could provide a low energy pathway for ion translocation through the lipid bilayer, polyamino acids were incorporated into extruded liposomes and planar lipid membranes, and proton translocation was measured. Liposomes with incorporated long-chain poly-L-alanine or poly-L-leucine were found to have proton permeability coefficients 5 to 7 times greater than control liposomes, whereas short-chain polyamino acids had relatively little effect. Potassium permeability was not increased markedly by any of the polyamino acids tested. Analytical thin layer chromatography measurements of lipid content and a fluorescamine assay for amino acids showed that there were approximately 135 polyleucine or 65 polyalanine molecules associated with each liposome. Fourier transform infrared spectroscopy indicated that a major fraction of the long-chain hydrophobic peptides existed in an alpha-helical conformation. Single-channel recording in both 0.1 N HCl and 0.1 M KCl was also used to determine whether proton-conducting channels formed in planar lipid membranes (phosphatidylcholine/phosphatidylethanolamine, 1:1). Poly-L-leucine and poly-L-alanine in HCl caused a 10- to 30-fold increase in frequency of conductive events compared to that seen in KCl or by the other polyamino acids in either solution. This finding correlates well with the liposome observations in which these two polyamino acids caused the largest increase in membrane proton permeability but had little effect on potassium permeability. Poly-L-leucine was considerably more conductive than poly-L-alanine due primarily to larger event amplitudes and, to a lesser extent, a higher event frequency. Poly-L-leucine caused two
A high-flow holweck pump for fusion applications

International Nuclear Information System (INIS)

Iseli, M.; Dinner, P.J.; Murdoch, D.K.

1995-01-01

Present concepts for power reactors require high pumping speed for the torus exhaust (10 5 -10 6 1/s) with low tritium inventories. Conventional approaches using Compound Cryopumps necessitate high tritium inventories and Turbomolecular pumps require large scale-up in throughput and are sensitive to eddy current heating of the rotor and sudden venting thrust. Cooling the gas to low temperature (20K) increases the gas density at the pump-entrance enough to obtain high throughputs from compact mechanical devices such as molecular drag pumps. A numerical model of such a pump and experimental results confirm the high pumping speed achievable with this concept. The model is used for extrapolation and optimisation of the design of a prototype. (orig.)
Considerations for reference pump curves

International Nuclear Information System (INIS)

Stockton, N.B.

1992-01-01

This paper examines problems associated with inservice testing (IST) of pumps to assess their hydraulic performance using reference pump curves to establish acceptance criteria. Safety-related pumps at nuclear power plants are tested under the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code (the Code), Section 11. The Code requires testing pumps at specific reference points of differential pressure or flow rate that can be readily duplicated during subsequent tests. There are many cases where test conditions cannot be duplicated. For some pumps, such as service water or component cooling pumps, the flow rate at any time depends on plant conditions and the arrangement of multiple independent and constantly changing loads. System conditions cannot be controlled to duplicate a specific reference value. In these cases, utilities frequently request to use pump curves for comparison of test data for acceptance. There is no prescribed method for developing a pump reference curve. The methods vary and may yield substantially different results. Some results are conservative when compared to the Code requirements; some are not. The errors associated with different curve testing techniques should be understood and controlled within reasonable bounds. Manufacturer's pump curves, in general, are not sufficiently accurate to use as reference pump curves for IST. Testing using reference curves generated with polynomial least squares fits over limited ranges of pump operation, cubic spline interpolation, or cubic spline least squares fits can provide a measure of pump hydraulic performance that is at least as accurate as the Code required method. Regardless of the test method, error can be reduced by using more accurate instruments, by correcting for systematic errors, by increasing the number of data points, and by taking repetitive measurements at each data point
Energy pumping analysis of skating motion in a half pipe and on a level surface

Science.gov (United States)

Feng, Z. C.; Xin, Ming

2015-01-01

In this paper, an energy pumping mechanism for locomotion is analysed. The pumping is accomplished by exerting forces perpendicular to the direction of motion. The paper attempts to demonstrate an interesting application of the classical mechanics to two sporting events: a person skating in a half pipe and a person travelling on a level surface on a skateboard. The equations of motion based on simplified mechanical models are derived using the Lagrange mechanics. The energy-pumping phenomenon is revealed through numerical simulations with simple pumping actions. The result presented in this paper can be used as an interesting class project in undergraduate mechanics or physics courses. It also motivates potential new applications of energy pumping in many engineering fields.
A highly self-adaptive cold plate for the single-phase mechanically pumped fluid loop for spacecraft thermal management

International Nuclear Information System (INIS)

Wang, Ji-Xiang; Li, Yun-Ze; Zhang, Hong-Sheng; Wang, Sheng-Nan; Liang, Yi-Hao; Guo, Wei; Liu, Yang; Tian, Shao-Ping

2016-01-01

Highlights: • A highly self-adaptive cold plate integrated with paraffin-based actuator is proposed. • Higher operating economy is attained due to an energy-efficient strategy. • A greater compatibility of the current space control system is obtained. • Model was entrenched theoretically to design the system efficiently. • A strong self-adaptability of the cold plate is observed experimentally. - Abstract: Aiming to improve the conventional single-phase mechanically pumped fluid loop applied in spacecraft thermal control system, a novel actively-pumped loop using distributed thermal control strategy was proposed. The flow control system for each branch consists primarily of a thermal control valve integrated with a paraffin-based actuator residing in the front part of each corresponding cold plate, where both coolant’s flow rate and the cold plate’s heat removal capability are well controlled sensitively according to the heat loaded upon the cold plate due to a conversion between thermal and mechanical energies. The operating economy enhances remarkably owing to no energy consumption in flow control process. Additionally, realizing the integration of the sensor, controller and actuator systems, it simplifies structure of the traditional mechanically pumped fluid loop as well. Revolving this novel scheme, mathematical model regarding design process of the highly specialized cold plate was entrenched theoretically. A validating system as a prototype was established on the basis of the design method and the scheduled objective of the controlled temperature (43 °C). Then temperature control performances of the highly self-adaptive cold plate under various operating conditions were tested experimentally. During almost all experiments, the controlled temperature remains within a range of ±2 °C around the set-point. Conclusions can be drawn that this self-driven control system is stable with sufficient fast transient responses and sufficient small steady
On the Significance of the Upcoming Large Hadron Collider Proton-Proton Cross Section Data

Directory of Open Access Journals (Sweden)

Comay E.

2010-04-01

Full Text Available The relevance of the Regular Charge-Monopole Theory to the proton structure is described. The discussion relies on classicalelectrodynamics and its associated quantum mechanics. Few experimental data are used as a clue to the specific structure of baryons. This basis provides an explanation for the shape of the graph of the pre-LHC proton-proton cross section data. These data also enable a description of the significance of the expected LHC cross section measurements which will be known soon. Problematic QCD issues are pointed out.
The Energy Budget of Steady-State Photosynthesis

Energy Technology Data Exchange (ETDEWEB)

Kramer, David

2007-06-30

Our work developed a unique set of in vivo spectroscopic tools that have allowed us to probe the importance of 1) The effects of storage of proton motive force (pmf ) in the form of both electric field (Δψ) and pH difference (ΔpH); 2) alteration in the stoichiometry of proton pumping to electron transfer at key steps; 3) the influence of changes in the conductivity for proton efflux from the thylakoid of the ATP synthase; 4) the mechanisms of steps of the electron transfer process that pump protons; and 5) the mechanisms by which reactive O{sub 2} is generated as a side reaction to photosynthesis, and how these processes are minimized.
The effects of irradiation and proton implantation on the density of mobile protons in SiO2 films

International Nuclear Information System (INIS)

Vanheusden, K.

1998-04-01

Proton implantation into the buried oxide of Si/SiO 2 /Si structures does not introduce mobile protons. The cross section for capture of radiation-induced electrons by mobile protons is two orders of magnitude smaller than for electron capture by trapped holes. The data provide new insights into the atomic mechanisms governing the generation and radiation tolerance of mobile protons in SiO 2 . This can lead to improved techniques for production and radiation hardening of radiation tolerant memory devices

Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach.

Science.gov (United States)

Rohof, Wout O; Bennink, Roelof J; Boeckxstaens, Guy E

2014-07-01

The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Thirty-six patients with GERD (18 not taking PPIs, 18 taking PPIs; 19 men; age, 55 ± 2.1 y) were analyzed by concurrent high-resolution manometry and pH-impedance monitoring after a standardized meal. The acid pocket was visualized using scintigraphy after intravenous administration of (99m)technetium-pertechnetate. The size of the acid pocket was measured and its position was determined, relative to the diaphragm, using radionuclide markers on a high-resolution manometry catheter. At the end of the study, the acid pocket was aspirated, and its pH level was measured. The number of reflux episodes was comparable between patients on and off PPIs, but the number of acid reflux episodes was reduced significantly in patients on PPIs. In patients on PPIs, the acid pocket was smaller and more frequently located below the diaphragm. The mean pH of the acid pocket was significantly lower in patients not taking PPIs (n = 6) than in those who were (n = 16) (0.9; range, 0.7-1.2 vs 4.0; range, 1.6-5.9; P pH of acid pockets correlated significantly with the lowest pH values measured for refluxate (r = 0.72; P < .01). Based on analyses of acid pockets in patients with GERD, the acid pocket appears to be a reservoir from which reflux occurs when patients are receiving PPIs. PPIs might affect the size, acidity, or position of the acid pocket, which contributes to the efficacy in patients with GERD. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
Carbon-concentrating mechanisms in seagrasses.

Science.gov (United States)

Larkum, Anthony William D; Davey, Peter A; Kuo, John; Ralph, Peter J; Raven, John A

2017-06-01

Seagrasses are unique angiosperms that carry out growth and reproduction submerged in seawater. They occur in at least three families of the Alismatales. All have chloroplasts mainly in the cells of the epidermis. Living in seawater, the supply of inorganic carbon (Ci) to the chloroplasts is diffusion limited, especially under unstirred conditions. Therefore, the supply of CO2 and bicarbonate across the diffusive boundary layer on the outer side of the epidermis is often a limiting factor. Here we discuss the evidence for mechanisms that enhance the uptake of Ci into the epidermal cells. Since bicarbonate is plentiful in seawater, a bicarbonate pump might be expected; however, the evidence for such a pump is not strongly supported. There is evidence for a carbonic anhydrase outside the outer plasmalemma. This, together with evidence for an outward proton pump, suggests the possibility that local acidification leads to enhanced concentrations of CO2 adjacent to the outer tangential epidermal walls, which enhances the uptake of CO2, and this could be followed by a carbon-concentrating mechanism (CCM) in the cytoplasm and/or chloroplasts. The lines of evidence for such an epidermal CCM are discussed, including evidence for special 'transfer cells' in some but not all seagrass leaves in the tangential inner walls of the epidermal cells. It is concluded that seagrasses have a CCM but that the case for concentration of CO2 at the site of Rubisco carboxylation is not proven. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Theoretical Insights Into the Excited State Double Proton Transfer Mechanism of Deep Red Pigment Alkannin.

Science.gov (United States)

Zhao, Jinfeng; Dong, Hao; Zheng, Yujun

2018-02-08

As the most important component of deep red pigments, alkannin is investigated theoretically in detail based on time-dependent density functional theory (TDDFT) method. Exploring the dual intramolecular hydrogen bonds (O1-H2···O3 and O4-H5···O6) of alkannin, we confirm the O1-H2···O3 may play a more important role in the first excited state than the O4-H5···O6 one. Infrared (IR) vibrational analyses and subsequent charge redistribution also support this viewpoint. Via constructing the S 1 -state potential energy surface (PES) and searching transition state (TS) structures, we illuminate the excited state double proton transfer (ESDPT) mechanism of alkannin is the stepwise process that can be first launched by the O1-H2···O3 hydrogen bond wire in gas state, acetonitrile (CH 3 CN) and cyclohexane (CYH) solvents. We present a novel mechanism that polar aprotic solvents can contribute to the first-step proton transfer (PT) process in the S 1 state, and nonpolar solvents play important roles in lowering the potential energy barrier of the second-step PT reaction.
A Linear Electromagnetic Piston Pump

Science.gov (United States)

Hogan, Paul H.

Advancements in mobile hydraulics for human-scale applications have increased demand for a compact hydraulic power supply. Conventional designs couple a rotating electric motor to a hydraulic pump, which increases the package volume and requires several energy conversions. This thesis investigates the use of a free piston as the moving element in a linear motor to eliminate multiple energy conversions and decrease the overall package volume. A coupled model used a quasi-static magnetic equivalent circuit to calculate the motor inductance and the electromagnetic force acting on the piston. The force was an input to a time domain model to evaluate the mechanical and pressure dynamics. The magnetic circuit model was validated with finite element analysis and an experimental prototype linear motor. The coupled model was optimized using a multi-objective genetic algorithm to explore the parameter space and maximize power density and efficiency. An experimental prototype linear pump coupled pistons to an off-the-shelf linear motor to validate the mechanical and pressure dynamics models. The magnetic circuit force calculation agreed within 3% of finite element analysis, and within 8% of experimental data from the unoptimized prototype linear motor. The optimized motor geometry also had good agreement with FEA; at zero piston displacement, the magnetic circuit calculates optimized motor force within 10% of FEA in less than 1/1000 the computational time. This makes it well suited to genetic optimization algorithms. The mechanical model agrees very well with the experimental piston pump position data when tuned for additional unmodeled mechanical friction. Optimized results suggest that an improvement of 400% of the state of the art power density is attainable with as high as 85% net efficiency. This demonstrates that a linear electromagnetic piston pump has potential to serve as a more compact and efficient supply of fluid power for the human scale.
Coronal heating driven by a magnetic gradient pumping mechanism in solar plasmas

Energy Technology Data Exchange (ETDEWEB)

Tan, Baolin, E-mail: bltan@nao.cas.cn [Key Laboratory of Solar Activity, National Astronomical Observatories of Chinese Academy of Sciences, Beijing 100012 (China)

2014-11-10

The heating of the solar corona is a longstanding mystery in astrophysics. Considering that the solar magnetic field is spatially inhomogeneous with a considerable magnetic gradient from the solar surface to the corona, this work proposes a magnetic gradient pumping (MGP) mechanism to try to explain the formation of hot plasma upflows, such as hot type II spicules and hot plasma ejections. In the MGP mechanism, the magnetic gradient may drive the energetic particles to move upward from the underlying solar atmosphere and form hot upflows. These upflow energetic particles are deposited in the corona, causing it to become very hot. Rough estimations indicate that the solar corona can be heated to above 1 million degrees, and the upflow velocity is about 40 km s{sup –1} in the chromosphere and about 130 km s{sup –1} in the corona. The solar magnetic flux tubes act as pumpers to extract energetic particles from the underlying thermal photosphere, convey them, and deposit them in the corona. The deposit of these energetic particles causes the corona to become hot, and the escape of such particles from the photosphere leaves it a bit cold. This mechanism can present a natural explanation to the mystery of solar coronal heating.
Countermeasure against thermal fatigue crack of primary loop recirculation pump in BWR

International Nuclear Information System (INIS)

Noda, Hiroshi; Narabayashi, Tadashi; Takahashi, Yuuji

2008-01-01

The reactor water was fed to the purge water of the mechanical seal on the original design of the primary loop recirculation pump. Because the mechanical seal had a short life due to the cruds in the reactor water, the clean purge water was adopted instead of the reactor water. After this modification, the shallow cracks were found on the surface of the pump shaft and casing cover due to the temperature fluctuation between the cold purge water and the hot pump discharge water. The fundamental mechanism and countermeasure were investigated by scale test, mock-up test and so on. The flow barrier with a heater was contrived through these tests. It has been introduced gradually in operating and constructing PLR pumps after its completion in 1995. The PLR pumps are overhauled around every 10 years in Japan. The first overhaul of the PLR pumps showed no cracks around the pump shaft and casing over after 10 years' operation. This paper presents both its development process and inspection results. (author)
Clarification on the decarboxylation mechanism in KasA based on the protonation state of key residues in the acyl-enzyme state.

Science.gov (United States)

Lee, Wook; Engels, Bernd

2013-07-11

The β-ketoacyl ACP synthase I (KasA) is a promising drug target because it is essential for the survival of Mycobacterium tuberculosis , a causative agent of tuberculosis. It catalyzes a condensation reaction that comprises three steps. The resulting elongated acyl chains are subsequently needed for the cell wall construction. While the mechanism of the first step (acylation of Cys171 in the active site) is straightforward already, the second step (decarboxylation of malonyl substrate) has been controversial due to the difficulty in determining the correct protonation states of the involved residues (His311, His345, Lys340, Glu354). Available experimental data suggest three possible mechanisms which differ considerably. They are not consistent with each other because these studies could not be performed for KasA at the beginning of decarboxylation step (acyl-enzyme state of KasA). Instead, different mutants had to be used which are expected to resemble this situation. In this first computational study about this topic, we use the free energy perturbation (FEP) method to compute the relevant pKa values in the acyl-enzyme state of KasA and use molecular dynamics (MD) simulations to rationalize the results. Subsequent density functional theory (DFT)-based quantum mechanical/molecular mechanical (QM/MM) MD simulations and umbrella samplings have been used to disentangle the close relationships between the protonation states of the involved residues. By these simulations, we can address the preferred protonation states and roles of the residues involved in decarboxylation reaction, thereby suggesting the possible mechanism for the decarboxylation step.
Poly(dA-dT).poly(dA-dT) two-pathway proton exchange mechanism. Effect of general and specific base catalysis on deuteration rates

International Nuclear Information System (INIS)

Hartmann, B.; Leng, M.; Ramstein, J.

1986-01-01

The deuteration rates of the poly(dA-dT).poly(dA-dT) amino and imino protons have been measured with stopped-flow spectrophotometry as a function of general and specific base catalyst concentration. Two proton exchange classes are found with time constants differing by a factor of 10 (4 and 0.4 s-1). The slower class represents the exchange of the adenine amino protons whereas the proton of the faster class has been assigned to the thymine imino proton. The exchange rates of these two classes of protons are independent of general and specific base catalyst concentration. This very characteristic behavior demonstrates that in our experimental conditions the exchange rates of the imino and amino protons in poly(dA-dT).poly(dA-dT) are limited by two different conformational fluctuations. We present a three-state exchange mechanism accounting for our experimental results
Esophageal Motility and Rikkunshito Treatment for Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease: A Prospective, Uncontrolled, Open-Label Pilot Study Trial.

Science.gov (United States)

Odaka, Takeo; Yamato, Shigeru; Yokosuka, Osamu

2017-01-01

Only a few reports focused on esophageal motility in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) and there has been no established strategy for treatment. To clarify the characteristics of esophageal motility in patients with PPI-refractory NERD, we evaluated esophageal function using combined multichannel intraluminal impedance and esophageal manometry (MII-EM). In addition, we evaluated the efficacy of rikkunshito (RKT), which is a gastrointestinal prokinetic agent. Thirty patients with NERD were enrolled and underwent MII-EM. After 8 weeks of RKT (7.5 g/d) treatment, MII-EM was repeated on patients with PPI-refractory NERD. Symptoms were assessed by the Gastrointestinal Symptom Rating Scale. In patients with PPI-refractory NERD, measures of complete bolus transit, peristaltic contractions, and residual pressure of the lower esophageal sphincter during swallowing deviated from the standard values and esophageal clearance was found to be deteriorated. RKT significantly improved the peristaltic contractions ( P esophageal sphincter ( P disorders of esophageal and lower esophageal sphincter motility that were improved by RKT. Further studies examining esophageal motor activity of RKT in PPI-refractory NERD are required. University hospital Medical Information Network (UMIN) Clinical Trial Registry identifier: UMIN000003092.
Proton Conductive Channel Optimization in Methanol Resistive Hybrid Hyperbranched Polyamide Proton Exchange Membrane

Directory of Open Access Journals (Sweden)

Liying Ma

2017-12-01

Full Text Available Based on a previously developed polyamide proton conductive macromolecule, the nano-scale structure of the self-assembled proton conductive channels (PCCs is adjusted via enlarging the nano-scale pore size within the macromolecules. Hyperbranched polyamide macromolecules with different size are synthesized from different monomers to tune the nano-scale pore size within the macromolecules, and a series of hybrid membranes are prepared from these two micromoles to optimize the PCC structure in the proton exchange membrane. The optimized membrane exhibits methanol permeability low to 2.2 × 10−7 cm2/s, while the proton conductivity of the hybrid membrane can reach 0.25 S/cm at 80 °C, which was much higher than the value of the Nafion 117 membrane (0.192 S/cm. By considering the mechanical, dimensional, and the thermal properties, the hybrid hyperbranched polyamide proton exchange membrane (PEM exhibits promising application potential in direct methanol fuel cells (DMFC.
A method of applying two-pump system in automatic transmissions for energy conservation

Directory of Open Access Journals (Sweden)

Peng Dong

2015-06-01

Full Text Available In order to improve the hydraulic efficiency, modern automatic transmissions tend to apply electric oil pump in their hydraulic system. The electric oil pump can support the mechanical oil pump for cooling, lubrication, and maintaining the line pressure at low engine speeds. In addition, the start–stop function can be realized by means of the electric oil pump; thus, the fuel consumption can be further reduced. This article proposes a method of applying two-pump system (one electric oil pump and one mechanical oil pump in automatic transmissions based on the forward driving simulation. A mathematical model for calculating the transmission power loss is developed. The power loss transfers to heat which requires oil flow for cooling and lubrication. A leakage model is developed to calculate the leakage of the hydraulic system. In order to satisfy the flow requirement, a flow-based control strategy for the electric oil pump is developed. Simulation results of different driving cycles show that there is a best combination of the size of electric oil pump and the size of mechanical oil pump with respect to the optimal energy conservation. Besides, the two-pump system can also satisfy the requirement of the start–stop function. This research is extremely valuable for the forward design of a two-pump system in automatic transmissions with respect to energy conservation and start–stop function.
Energy pumping analysis of skating motion in a half pipe and on a level surface

International Nuclear Information System (INIS)

Feng, Z C; Xin, Ming

2015-01-01

In this paper, an energy pumping mechanism for locomotion is analysed. The pumping is accomplished by exerting forces perpendicular to the direction of motion. The paper attempts to demonstrate an interesting application of the classical mechanics to two sporting events: a person skating in a half pipe and a person travelling on a level surface on a skateboard. The equations of motion based on simplified mechanical models are derived using the Lagrange mechanics. The energy-pumping phenomenon is revealed through numerical simulations with simple pumping actions. The result presented in this paper can be used as an interesting class project in undergraduate mechanics or physics courses. It also motivates potential new applications of energy pumping in many engineering fields. (paper)
Increase of weakly acidic gas esophagopharyngeal reflux (EPR) and swallowing-induced acidic/weakly acidic EPR in patients with chronic cough responding to proton pump inhibitors.

Science.gov (United States)

Kawamura, O; Shimoyama, Y; Hosaka, H; Kuribayashi, S; Maeda, M; Nagoshi, A; Zai, H; Kusano, M

2011-05-01

Gastro-esophageal reflux disease (GERD)-related chronic cough (CC) may have multifactorial causes. To clarify the characteristics of esophagopharyngeal reflux (EPR) events in CC patients whose cough was apparently influenced by gastro-esophageal reflux (GER), we studied patients with CC clearly responding to full-dose proton pump inhibitor (PPI) therapy (CC patients). Ten CC patients, 10 GERD patients, and 10 healthy controls underwent 24-h ambulatory pharyngo-esophageal impedance and pH monitoring. Weakly acidic reflux was defined as a decrease of pH by >1 unit with a nadir pH >4. In six CC patients, monitoring was repeated after 8 weeks of PPI therapy. The number of each EPR event and the symptom association probability (SAP) were calculated. Symptoms were evaluated by a validated GERD symptom questionnaire. Weakly acidic gas EPR and swallowing-induced acidic/weakly acidic EPR only occurred in CC patients, and the numbers of such events was significantly higher in the CC group than in the other two groups (P pump inhibitor therapy abolished swallowing-induced acidic/weakly acidic EPR, reduced weakly acidic gas EPR, and improved symptoms (all P gas EPR and swallowing-induced acidic/weakly acidic EPR. A direct effect of acidic mist or liquid refluxing into the pharynx may contribute to chronic cough, while cough may also arise indirectly from reflux via a vago-vagal reflex in some patients. © 2011 Blackwell Publishing Ltd.
Advanced performance of small diaphragm vacuum pumps through the use of mechatronics

Science.gov (United States)

Lachenmann, R.; Dirscherl, J.

Oil-free diaphragm vacuum pumps have proven to be the best way in vacuum generation for the chemical laboratory and they also find increasing use as backing pumps for modern wide-range turbo molecular pumps. The majority of vacuum pumps in practical use pump only a rather small percentage of their lifetime at full gas load. A pump backing a turbo molecular pump does not have to pump a significant gas load when the high-vacuum pump is running at ultimate vacuum pressure. Also, for a vacuum distillation the vacuum pump has to operate at full speed only at the beginning to lower the pressure inside the system to a vacuum level where evaporation starts. In a rather leak-tight system the distillation process continues by evaporating from the hot liquid and condensing at the cold condenser without the need of a mechanical vacuum pump. Rotational speed controlled diaphragm pumps are now available through progress in mechatronics and offer high pumping speed capability for fast pump-down cycles and precise pressure control for distillations. At low gas load the rotational speed can be reduced, improving maintenance intervals, power consumption, noise, vibration and - surprisingly - also ultimate pressure. The different behaviour in pumping speed and ultimate pressure of rotational speed controlled diaphragm pumps in comparison to constant-speed pumps is related to the mechanical properties of the valves and gas dynamics .
Enzyme-Powered Pumps: From Fundamentals to Applications

Science.gov (United States)

Ortiz-Rivera, Isamar

Non-mechanical nano and microfluidic devices that function without the aid of an external power source, and can be tailored to meet specific needs, represent the next generation of smart devices. Recently, we have shown that surface-bound enzymes can act as pumps driving large-scale fluid flows in the presence of any substance that triggers the enzymatic reaction (e.g. substrate, co-factor, or biomarker). The fluid velocities attained in such systems depend directly on the enzymatic reaction rate and the concentration of the substance that initiates enzymatic catalysis. The use of biochemical reactions to power a micropump offers the advantages of specificity, sensitivity, and selectively, eliminating at the same time the need of an external power source, while providing biocompatibility. More importantly, these self-powered pumps overcome a significant obstacle in nano- and micro-fluidics: the need to use external pressure-driven pumps to push fluids through devices. Certainly, the development of enzyme-powered devices opens up new venues in biochemical engineering, particularly in the biomedical field. The work highlighted in this dissertation covers all the studies performed with enzyme-powered pumps, from the development of the micropump design, to the efforts invested in understanding the enzyme pump concept as a whole. The data collected to date, aims to expand our knowledge about enzyme-powered micropumps from the inside out: not only by exploring the different applications of these devices at the macroscale, but also by investigating in depth the mechanism of pump activation behind these systems. Specifically, we have focused on: (1) The general features that characterize the pumping behavior observed in enzyme-powered pumps, as well as the optimization of the device, (2) the possible mechanisms behind fluid motion, including the role of enzyme coverage and/or activity on the transduction of chemical energy into mechanical fluid flow in these devices
Main coolant pump testing at Ontario Hydro

International Nuclear Information System (INIS)

Hartlen, R.

1991-01-01

This article describes Ontario Hydro Research Division's experience with a computerized data acquisition and analysis system for monitoring mechanical vibration in reactor coolant pumps. The topics covered include bench-marking of the computer system and the coolant pumps, signatures of normal and malfunctioning pumps, analysis of data collected by the monitoring system, simulation of faults, and concerns that have been expressed about data interpretation, sensor types and locations, alarm/shutdown limits and confirmation of nondestructive examination testing. This presentation consists of overheads only
Tendency of nuclear pumps for PWR primary system

International Nuclear Information System (INIS)

Shibata, Takeshi

1976-01-01

At present, large PWR power stations of more than 1,000 MW are successively constructed, and the pumps used there have become large. The progress and tendency of the technical development of main pumps in primary system are described. The increase of the capacity of power stations is accomplished by increasing the circulating coolant quantity per loop or the number of loops. Same standard primary coolant pumps are employed in the plants from 500 to 1,100 MW. The type of primary coolant pumps changed from canned type to shaft seal type, and the advantages of the shaft seal type are cheap production cost, high efficiency, and the easy utilization of inertia force. The bearings and shaft seals are thermally insulated from primary coolant. As for auxiliary pumps, reciprocating filling-up pumps and centrifugal high pressure injection pumps are used for 500 MW plants, but only centrifugal pumps are used for both purposes in 800 MW plants, and in 1,100 MW plants, the pumps of both types for separate purposes and centrifugal pumps for combined purposes are installed. Horizontal or vertical pumps of same type are used as containment vessel-spraying pumps and excess heat-eliminating pumps. The type of boric acid pumps changed from canned type to mechanical seal type. (Kako, I.)
Association between baseline impedance values and response proton pump inhibitors in patients with heartburn.

Science.gov (United States)

de Bortoli, Nicola; Martinucci, Irene; Savarino, Edoardo; Tutuian, Radu; Frazzoni, Marzio; Piaggi, Paolo; Bertani, Lorenzo; Furnari, Manuele; Franchi, Riccardo; Russo, Salvatore; Bellini, Massimo; Savarino, Vincenzo; Marchi, Santino

2015-06-01

Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for
Role of Acid and Weakly Acidic Reflux in Gastroesophageal Reflux Disease Off Proton Pump Inhibitor Therapy

Science.gov (United States)

Sung, Hea Jung; Moon, Sung Jin; Kim, Jin Su; Lim, Chul Hyun; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gye

2012-01-01

Background/Aims Available data about reflux patterns and symptom determinants in the gastroesophageal reflux disease (GERD) subtypes off proton pump inhibitor (PPI) therapy are lacking. We aimed to evaluate reflux patterns and determinants of symptom perception in patients with GERD off PPI therapy by impedance-pH monitoring. Methods We retrospectively reviewed the impedance-pH data in patients diagnosed as GERD based on results of impedance-pH monitoring, endoscopy and/or typical symptoms. The characteristics of acid and weakly acidic reflux were evaluated. Symptomatic and asymptomatic reflux were compared according to GERD subtypes and individual symptoms. Results Forty-two patients (22 males, mean age 46 years) were diagnosed as GERD (17 erosive reflux disease, 9 pH(+) non-erosive reflux disease [NERD], 9 hypersensitive esophagus and 7 symptomatic NERD). A total of 1,725 reflux episodes were detected (855 acid [50%], 857 weakly acidic [50%] and 13 weakly alkaline reflux [reflux was more frequently symptomatic and bolus clearance was longer compared with weakly acidic reflux. In terms of globus, weakly acidic reflux was more symptomatic. Symptomatic reflux was more frequently acid and mixed reflux; these associations were more pronounced in erosive reflux disease and symptomatic NERD. The perception of regurgitation was related to acid reflux, while that of globus was more related to weakly acidic reflux. Conclusions In patients not taking PPI, acid reflux was more frequently symptomatic and had longer bolus clearance. Symptomatic reflux was more frequently acid and mixed type; however, weakly acidic reflux was associated more with globus. These data suggest a role for impedance-pH data in the evaluation of globus. PMID:22837877
Use of Proton-Pump Inhibitors Predicts Heart Failure and Death in Patients with Coronary Artery Disease.

Directory of Open Access Journals (Sweden)

Ana María Pello Lázaro

Full Text Available Proton-pump inhibitors (PPIs seem to increase the incidence of cardiovascular events in patients with coronary artery disease (CAD, mainly in those using clopidogrel. We analysed the impact of PPIs on the prognosis of patients with stable CAD.We followed 706 patients with CAD. Primary outcome was the combination of secondary outcomes. Secondary outcomes were 1 acute ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack and 2 heart failure (HF or death.Patients on PPIs were older [62.0 (53.0-73.0 vs. 58.0 (50.0-70.0 years; p = 0.003] and had a more frequent history of stroke (4.9% vs. 1.1%; p = 0.004 than those from the non-PPI group, and presented no differences in any other clinical variable, including cardiovascular risk factors, ejection fraction, and therapy with aspirin and clopidogrel. Follow-up was 2.2±0.99 years. Seventy-eight patients met the primary outcome, 53 developed acute ischaemic events, and 33 HF or death. PPI use was an independent predictor of the primary outcome [hazard ratio (HR = 2.281 (1.244-4.183; p = 0.008], along with hypertension, body-mass index, glomerular filtration rate, atrial fibrillation, and nitrate use. PPI use was also an independent predictor of HF/death [HR = 5.713 (1.628-20.043; p = 0.007], but not of acute ischaemic events. A propensity score showed similar results.In patients with CAD, PPI use is independently associated with an increased incidence of HF and death but not with a high rate of acute ischaemic events. Further studies are needed to confirm these findings.

Role of Acid and weakly acidic reflux in gastroesophageal reflux disease off proton pump inhibitor therapy.

Science.gov (United States)

Sung, Hea Jung; Cho, Yu Kyung; Moon, Sung Jin; Kim, Jin Su; Lim, Chul Hyun; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gye

2012-07-01

Available data about reflux patterns and symptom determinants in the gastroesophageal reflux disease (GERD) subtypes off proton pump inhibitor (PPI) therapy are lacking. We aimed to evaluate reflux patterns and determinants of symptom perception in patients with GERD off PPI therapy by impedance-pH monitoring. We retrospectively reviewed the impedance-pH data in patients diagnosed as GERD based on results of impedance-pH monitoring, endoscopy and/or typical symptoms. The characteristics of acid and weakly acidic reflux were evaluated. Symptomatic and asymptomatic reflux were compared according to GERD subtypes and individual symptoms. Forty-two patients (22 males, mean age 46 years) were diagnosed as GERD (17 erosive reflux disease, 9 pH(+) non-erosive reflux disease [NERD], 9 hypersensitive esophagus and 7 symptomatic NERD). A total of 1,725 reflux episodes were detected (855 acid [50%], 857 weakly acidic [50%] and 13 weakly alkaline reflux [Acid reflux was more frequently symptomatic and bolus clearance was longer compared with weakly acidic reflux. In terms of globus, weakly acidic reflux was more symptomatic. Symptomatic reflux was more frequently acid and mixed reflux; these associations were more pronounced in erosive reflux disease and symptomatic NERD. The perception of regurgitation was related to acid reflux, while that of globus was more related to weakly acidic reflux. In patients not taking PPI, acid reflux was more frequently symptomatic and had longer bolus clearance. Symptomatic reflux was more frequently acid and mixed type; however, weakly acidic reflux was associated more with globus. These data suggest a role for impedance-pH data in the evaluation of globus.
PREFACE: Transport phenomena in proton conducting media Transport phenomena in proton conducting media

Science.gov (United States)

Eikerling, Michael

2011-06-01

Proton transport phenomena are of paramount importance for acid-base chemistry, energy transduction in biological organisms, corrosion processes, and energy conversion in electrochemical systems such as polymer electrolyte fuel cells. The relevance for such a plethora of materials and systems, and the ever-lasting fascination with the highly concerted nature of underlying processes drive research across disciplines in chemistry, biology, physics and chemical engineering. A proton never travels alone. Proton motion is strongly correlated with its environment, usually comprised of an electrolyte and a solid or soft host material. For the transport in nature's most benign proton solvent and shuttle, water that is, insights from ab initio simulations, matured over the last 15 years, have furnished molecular details of the structural diffusion mechanism of protons. Excess proton movement in water consists of sequences of Eigen-Zundel-Eigen transitions, triggered by hydrogen bond breaking and making in the surrounding water network. Nowadays, there is little debate about the validity of this mechanism in water, which bears a stunning resemblance to the basic mechanistic picture put forward by de Grotthuss in 1806. While strong coupling of an excess proton with degrees of freedom of solvent and host materials facilitates proton motion, this coupling also creates negative synergies. In general, proton mobility in biomaterials and electrochemical proton conducting media is highly sensitive to the abundance and structure of the proton solvent. In polymer electrolyte membranes, in which protons are bound to move in nano-sized water-channels, evaporation of water or local membrane dehydration due to electro-osmotic coupling are well-known phenomena that could dramatically diminish proton conductivity. Contributions in this special issue address various vital aspects of the concerted nature of proton motion and they elucidate important structural and dynamic effects of solvent
Evaluation of benzene exposure in petrol pump attendants and in mechanics by urinary trans, trans-muconic acid (t, t-MA determination

Directory of Open Access Journals (Sweden)

Teresa Cirillo

2004-12-01

Full Text Available
Occupational exposure to benzene in petrol pump attendants and in mechanics was studied by examining the benzene content in both the air breathed and in the urinary metabolite trans,trans-muconic acid (t,t-MA. Thirty petrol pump attendants and thirty mechanics (as exposed workers and thirty adult male office workers (as non exposed workers were involved in the study. Measures were taken at the begin and at the end of the working shifts.
The benzene concentrations in the breathing air samples varied from 2 to 88 μg m-3, lower than the EU acceptable limit for occupational environment. The average urinary t,t-MA in the petrol pump attendants at the begin and at the end of the working shifts ranged between 133 ± 69 and 255 ± 174 μg g-1 creatinine and in the mechanics between 204 ± 139 and 300 ± 211 μg g-1 creatinine, respectively.
In all the participants the mean levels of urinary t,t-MA at the end of the working shifts were significantly higher than those at the beginning. In the exposed workers mean levels of urinary t,t-MA were significantly higher than in those of the non-exposed workers. The influence of the smoking was demonstrated by the urinary t,t-MA levels in smoking non-exposed subjects.
Demonstration and Validation of Corrosion-Mitigation Technologies for Mechanical Room Utility Piping and Cooling-Tower Pumps

Science.gov (United States)

2015-05-01

34advanced material for cooling pump shafts" Stainless steel (316 or 416 ) Floway Pump Company, Fresno, CA 316 or 416 stainless steel shafts to replace...pump 5 incorporating 316 stainless steel housing. .................................... 19 Figure 13. New pump 5 being installed...43 Figure 28. Pump 5 (316 Stainless Steel ), 12 months exposure. .......................................... 43
Operational experience with the TRIUMF optically pumped polarized H- ion source

International Nuclear Information System (INIS)

Schmor, P.W.; Buchmann, L.; Jayamanna, K.; Levy, C.D.P.; McDonald, M.; Ruegg, R.

1991-05-01

The initial goal of a polarized proton beam extracted from the TRIUMF cyclotron, having a current of 5 μA with 60% polarization, has been achieved with the development of the optically pumped polarized H - ion source. This beam is now being used to produce an intense secondary beam of polarized neutrons for the TRIUMF experimental program. Much of the recent development effort has addressed the reliability requirements for routine operation. This paper describes the results with emphasis on the laser stabilization subsystem, the modifications to the electron cyclotron resonance proton ion source (ECRIS), the sodium charge exchange cells and the development of a low energy polarimeter. Also discussed are the developments which should lead to a higher polarization. (Author) 7 refs
Balanced pressure gerotor fuel pump

Energy Technology Data Exchange (ETDEWEB)

Raney, Michael Raymond; Maier, Eugen

2004-08-03

A gerotor pump for pressurizing gasoline fuel is capable of developing pressures up to 2.0 MPa with good mechanical and volumetric efficiency and satisfying the durability requirements for an automotive fuel pump. The pump has been designed with optimized clearances and by including features that promote the formation of lubricating films of pressurized fuel. Features of the improved pump include the use of a shadow port in the side plate opposite the outlet port to promote balancing of high fuel pressures on the opposite sides of the rotors. Inner and outer rotors have predetermined side clearances with the clearances of the outer rotor being greater than those of the inner rotor in order to promote fuel pressure balance on the sides of the outer rotor. Support of the inner rotor and a drive shaft on a single bushing with bearing sleeves maintains concentricity. Additional features are disclosed.
Mechanisms of proton relay and product release by Class A β-lactamase at ultrahigh resolution

Energy Technology Data Exchange (ETDEWEB)

Lewandowski, Eric M. [Department of Molecular Medicine, University of South Florida College of Medicine, Tampa FL USA; Lethbridge, Kathryn G. [Department of Molecular Medicine, University of South Florida College of Medicine, Tampa FL USA; Sanishvili, Ruslan [GMCA@APS, X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, IL USA; Skiba, Joanna [Department of Organic Chemistry, Faculty of Chemistry, University of Lodz, Poland; Kowalski, Konrad [Department of Organic Chemistry, Faculty of Chemistry, University of Lodz, Poland; Chen, Yu [Department of Molecular Medicine, University of South Florida College of Medicine, Tampa FL USA

2017-11-20

The beta-lactam antibiotics inhibit penicillin-binding proteins (PBPs) by forming a stable, covalent, acyl-enzyme complex. During the evolution from PBPs to Class A beta-lactamases, the beta-lactamases acquired Glu166 to activate a catalytic water and cleave the acyl-enzyme bond. Here we present three product complex crystal structures of CTX-M-14 Class A beta-lactamase with a ruthenocene-conjugated penicillin-a 0.85 angstrom resolution structure of E166A mutant complexed with the penilloate product, a 1.30 angstrom resolution complex structure of the same mutant with the penicilloate product, and a 1.18 angstrom resolution complex structure of S70G mutant with a penicilloate product epimer-shedding light on the catalytic mechanisms and product inhibition of PBPs and Class A beta-lactamases. The E166A-penilloate complex captured the hydrogen bonding network following the protonation of the leaving group and, for the first time, unambiguously show that the ring nitrogen donates a proton to Ser130, which in turn donates a proton to Lys73. These observations indicate that in the absence of Glu166, the equivalent lysine would be neutral in PBPs and therefore capable of serving as the general base to activate the catalytic serine. Together with previous results, this structure suggests a common proton relay network shared by Class A beta-lactamases and PBPs, from the catalytic serine to the lysine, and ultimately to the ring nitrogen. Additionally, the E166A-penicilloate complex reveals previously unseen conformational changes of key catalytic residues during the release of the product, and is the first structure to capture the hydrolyzed product in the presence of an unmutated catalytic serine.
Proton Pump Inhibitors and the Risk for Fracture at Specific Sites: Data Mining of the FDA Adverse Event Reporting System.

Science.gov (United States)

Wang, Liwei; Li, Mei; Cao, Yuying; Han, Zhengqi; Wang, Xueju; Atkinson, Elizabeth J; Liu, Hongfang; Amin, Shreyasee

2017-07-17

Proton pump inhibitors (PPIs) are widely used to treat gastric acid-related disorders. Concerns have been raised about potential fracture risk, especially at the hip, spine and wrist. However, fracture risk at other bone sites has not been as well studied. We investigated the association between PPIs and specific fracture sites using an aggregated knowledge-enhanced database, the Food and Drug Administration Adverse Event Reporting System Data Mining Set (AERS-DM). Proportional reporting ratio (PRR) was used to detect statistically significant associations (signals) between PPIs and fractures. We analyzed both high level terms (HLT) and preferred terms (PT) for fracture sites, defined by MedDRA (Medical Dictionary for Regulatory Activities). Of PPI users reporting fractures, the mean age was 65.3 years and the female to male ratio was 3.4:1. Results revealed signals at multiple HLT and PT fracture sites, consistent for both sexes. These included fracture sites with predominant trabecular bone, not previously reported as being associated with PPIs, such as 'rib fractures', where signals were detected for overall PPIs as well as for each of 5 generic ingredients (insufficient data for dexlansoprazole). Based on data mining from AERS-DM, PPI use appears to be associated with an increased risk for fractures at multiple sites.
On the Signiﬁcance of the Upcoming Large Hadron Collider Proton-Proton Cross Section Data

Directory of Open Access Journals (Sweden)

Comay E.

2010-04-01

Full Text Available The relevance of the Regular Charge-Monopole Theory to the proton structure is de- scribed. The discussion relies on classical electrodynamics and its associated quantum mechanics. Few experimental data are used as a clue to the specific structure of baryons. This basis provides an explanation for the shape of the graph of the pre-LHC proton- proton cross section data. These data also enable a description of the significance of the expected LHC cross section measurements which will be known soon. Problematic QCD issues are pointed out.
Are proton-pump inhibitors harmful for the semen quality of men in couples who are planning pregnancy?

Science.gov (United States)

Huijgen, Nicole A; de Ridder, Maria A J; Verhamme, Katia M; Dohle, Gert R; Vanrolleghem, Ann M; Sturkenboom, Miriam C J M; Laven, Joop S E; Steegers-Theunissen, Régine P M

2016-12-01

To determine associations between proton-pump inhibitor (PPI) use and semen parameters in young men of couples who are planning pregnancy. Case-control study of a population-based registry. Not applicable. General practitioner patients comprising 2,473 men from couples planning pregnancy with a recorded semen analysis: 241 with a low total motile sperm count (TMSC ≤1) and 714 with TMSC >1 as matched controls. None. Exposure to PPI; PPI dosage. The study of data from between 1996 and 2013 from the Integrated Primary Care Information database in the Netherlands, which incorporates the medical records of 1.5 million patients from 720 general practitioners, found that the use of PPIs in the period between 12 and 6 months before semen analysis was associated with a threefold higher risk of low TMSC (odds ratio 2.96; 95% confidence interval 1.26-6.97) adjusted for age and other medication. Use of PPIs during the 6 months immediately before the semen analysis was not statistically significantly associated with low TMSC. The use of PPIs in the period 12 to 6 months preceding semen analysis is associated with a threefold higher risk of low TMSC, which suggests that a long-term increase in gastric pH results in a decline of sperm quality. This finding emphasizes the need for more preconceptional research and counseling on the potential effects of medication use on semen quality. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
The effects of proton pump inhibitors on autonomic tone in patients with erosive and non-erosive esophagitis.

Science.gov (United States)

Jones, E L; Perring, S; Khattab, A; Allenby-Smith, O

2016-05-01

Reduction in autonomic tone as measured by heart rate variability (HRV) has been associated with various inflammatory conditions including reflux disease. The nature of and permanence of this damage have not been fully assessed. Fourteen individuals with non-erosive reflux disease (NERD) and 10 individuals with erosive reflux disease (ERD) as identified on endoscopy were assessed for HRV prior to starting a course of proton pump inhibitor (PPI) therapy and 8 weeks from the start of PPI therapy. Reflux symptoms were significantly improved by PPI therapy (p = 0.001), with no significant difference in reflux symptoms between the NERD and ERD groups either before (p = 0.45) or following therapy (p = 0.17). The ERD group displayed reduced HRV prior to PPI therapy as compared with a non-symptomatic group. There was significant improvement of HRV resulting from PPI therapy in the ERD group as measured by inspiration/expiration ratio on forced breathing (p = 0.02), Valsalva ratio (p = 0.03), and extended metronome-guided breathing at 6 breaths per minute (p = 0.03). While a similar pattern was seen in the NERD group, the effects were not as strong and did not reach statistical significance. The results are consistent with a growing body of evidence that cardiac autonomic neuropathy as measured by HRV is associated with gastro-esophageal reflux disease and also suggest that successful treatment of the inflammation can lead to reversal of the deterioration of autonomic tone associated with that inflammation. © 2016 John Wiley & Sons Ltd.
Proton hopping mechanism in solid polymer electrolysis demonstrated by tritium enrichment and electro-osmotic drag measurement

International Nuclear Information System (INIS)

Saito, Masaaki; Imaizumi, Hiroshi; Kato, Norio; Ishii, Yoshiyuki; Saito, Keiichi

2010-01-01

Anomalies in tritium enrichment cannot be explained only by isotopic effects in water electrolysis. The temperature dependence of the enrichment factor had been reported as increasing with 1/T. However, the increase was difficult to explain on the basis of kinetics. In this study, electro-osmotic drag (EOD, number of water molecule accompanied by a proton) and tritium enrichment ratio were investigated using light water (H 2 O) and heavy water (D 2 O) by solid polymer electrolysis. The EOD decreased and tritium enrichment ratio increased at low temperature for H 2 O. Electrolysis showed no temperature dependence for D 2 O. It was revealed that proton hopping by a hydrogen bond network of water molecules (the Grotthuss mechanism) affects the temperature dependence of EOD and tritium enrichment in the case of H 2 O. (author)
Comparison and Analysis of Delirium Induced by Histamine H2 Receptor Antagonists and Proton Pump Inhibitors in Cancer Patients

Directory of Open Access Journals (Sweden)

Shiro Fujii

2012-07-01

Full Text Available Objective: H2 blockers have been reported to be responsible for drug-induced delirium. We compared the incidence of delirium between two groups of patients who were treated with H2 blockers (H2 group or proton pump inhibitors (PPI group for anastomotic ulcer prevention following surgical treatment of esophageal cancer. Method: The incidence and severity of delirium were retrospectively compared in patients of the H2 group (30 cases; age, 65.2 ± 8.1 years and the PPI group (30 cases; 65.2 ± 6.5 years. The diagnosis of delirium was based on the Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision. Delirium severity was rated on the Delirium Rating Scale (DRS. Results: The incidence of delirium was significantly lower in the PPI group than in the H2 group (p = 0.047. In the 11 patients from the H2 group who developed delirium, discontinuation of H2 blockers resulted in a significant reduction in the DRS score (p = 0.009. In three patients for whom H2 blockers were discontinued, DRS scores decreased by 50% or more three days after discontinuation compared to the prediscontinuation score. Conclusions: These results suggested that switching antiulcer drugs from H2 blockers to PPIs reduced delirium and thus provided an appropriate coping method for drug-induced delirium from antiulcer drugs.
Evaluation of costs accrued through inadvertent continuation of hospital-initiated proton pump inhibitor therapy for stress ulcer prophylaxis beyond hospital discharge: a retrospective chart review

Directory of Open Access Journals (Sweden)

Shin S

2015-04-01

Full Text Available Sooyoung Shin Ajou University College of Pharmacy, Yeongtong-gu, Suwon-si, Gyeonggi-do, South Korea Background: Stress ulcers and related upper gastrointestinal bleeding are well-known complications in intensive care unit (ICU patients. Proton pump inhibitor (PPI-based stress ulcer prophylaxis (SUP has been widely prescribed in noncritically ill patients who are at low risk for clinically significant bleeding, which is then injudiciously continued after hospital discharge. This study aimed to evaluate the incidence of inappropriate prescribing of PPI-based preventative therapy in ICU versus non-ICU patients that subsequently continued postdischarge, and to estimate the costs incurred by the unwarranted outpatient continuation of PPI therapy.Methods: A retrospective review of patient data at a major teaching hospital in Korea was performed. During the 4-year study period, adult patients who were newly initiated on PPI-based SUP during hospital admission and subsequently discharged on a PPI without a medical indication for such therapy were captured for data analysis. The incidence rates of inappropriate prescribing of PPIs were compared between ICU and non-ICU patients, and the costs associated with such therapy were also examined.Results: A total of 4,410 patients, more than half of the inpatient-initiated PPI users, were deemed to have been inadvertently prescribed a PPI at discharge in the absence of a medical need for acid suppression. The incidence of inappropriate outpatient continuation of the prophylaxis was higher among ICU patients compared with non-ICU patients (57.7% versus 52.2%, respectively; P=0.001. The total expenditure accrued through the continuation of nonindicated PPI therapy was approximately US$40,175.Conclusion: This study confirmed that excess usage of PPIs for SUP has spread to low-risk, non-ICU patients. The overuse of unwarranted PPI therapy can incur large health care expenditure, as well as clinical complications
Calcium uptake and proton transport by acidocalcisomes of Toxoplasma gondii.

Directory of Open Access Journals (Sweden)

Peter Rohloff

Full Text Available Acidocalcisomes are acidic calcium stores found in diverse organisms, being conserved from bacteria to humans. They possess an acidic matrix that contains several cations bound to phosphates, which are mainly present in the form of short and long polyphosphate chains. Their matrix is acidified through the action of proton pumps such as a vacuolar proton ATPase and a vacuolar proton pyrophosphatase. Calcium uptake occurs through a Ca(2+/H(+ countertransporting ATPase located in the membrane of the organelle. Acidocalcisomes have been identified in a variety of microorganisms, including Apicomplexan parasites such as Plasmodium and Eimeria species, and in Toxoplasma gondii. We report the purification and characterization of an acidocalcisome fraction from T. gondii tachyzoites after subcellular fractionation and further discontinuous iodixanol gradient purification. Proton and calcium transport activities in the fraction were characterized by fluorescence microscopy and spectrophotometric methods using acridine orange and arsenazo III, respectively. This work will facilitate the understanding of the function of acidocalcisomes in Apicomplexan parasites, as we can now isolate highly purified fractions that could be used for proteomic analysis to find proteins that may clarify the biogenesis of these organelles.
Proton irradiation effects on gallium nitride-based devices

Science.gov (United States)

Karmarkar, Aditya P.

Proton radiation effects on state-of-the-art gallium nitride-based devices were studied using Schottky diodes and high electron-mobility transistors. The device degradation was studied over a wide range of proton fluences. This study allowed for a correlation between proton irradiation effects between different types of devices and enhanced the understanding of the mechanisms responsible for radiation damage in GaN-based devices. Proton irradiation causes reduced carrier concentration and increased series resistance and ideality factor in Schottky diodes. 1.0-MeV protons cause greater degradation than 1.8-MeV protons because of their higher non-ionizing energy loss. The displacement damage in Schottky diodes recovers during annealing. High electron-mobility transistors exhibit extremely high radiation tolerance, continuing to perform up to a fluence of ˜1014 cm-2 of 1.8-MeV protons. Proton irradiation creates defect complexes in the thin-film structure. Decreased sheet carrier mobility due to increased carrier scattering and decreased sheet carrier density due to carrier removal by the defect centers are the primary damage mechanisms. Interface disorder at either the Schottky or the Ohmic contact plays a relatively unimportant part in overall device degradation in both Schottky diodes and high electron-mobility transistors.
Design and experimental characterization of an EM pump

International Nuclear Information System (INIS)

Kim, Hee Reyoung; Hong, Sang Hee

1999-01-01

Generally, an EM (electromagnetic) pump is been employed to circulate electrically conducting liquids by using the Lorentz force. Especially, at the liquid metal reactor (LMR), which uses liquid sodium with high electrical conductivity as a coolant, an EM pump is needed due to its advantages over a mechanical pump, such as no rotating parts, no noise, and simplicity. In this research, an EM pump of a pilot annular linear induction type with a flow rate of 200 l/min was designed by using the electrical equivalent-circuit method. The pump was designed and manufactured by considering material and environmental (high temperature and liquid sodium) requirements. The pump performance was experimentally characterized based on input currents, voltage, power, and frequency. Also, the theoretical prediction was compared with the experimental result
Mechanisms of isoform-specific Na/K pump regulation by short- and long-term adrenergic activation in rat ventricular myocytes.

Science.gov (United States)

Yin, Jian; Guo, Hui-Cai; Yu, Ding; Wang, Hui-Ci; Li, Jun-Xia; Wang, Yong-Li

2014-01-01

Many stressful conditions, including cardiovascular diseases, induce long-term elevations in circulating catecholamines, thereby leading to changes of the Na/K pump and thus affecting myocardial functions. However, only short-term adrenergic regulation of the Na/K pump has been reported. The present study is the first investigation of long-term adrenergic regulation of the Na/K pump and the potential mechanism. After acutely isolated Sprague-Dawley rat myocytes were incubated with noradrenaline or isoprenaline for 24 h, Na/K pump high- (IPH) and low-affinity current (IPL), α-isoform mRNA, and α-isoform protein were examined using patch-clamp, RT-PCR, and Western blotting techniques, respectively. After the short-term incubation, isoprenaline reduced the IPL through a PKA-dependent pathway that involves α1-isoform translocation from the membrane to early endosomes, and noradrenaline increased the IPH through a PKC-dependent pathway that involves α2-isoform translocation from late endosomes to the membrane. After long-term incubation, isoprenaline increased the IPL, α1-isoform mRNA, and α1-isoform protein, and noradrenaline reduced the IPH, α2-isoform mRNA, and α1-isoform protein through a PKA-or PKC-dependent pathway, respectively. These results suggest that long-term adrenergic Na/K pump regulation is isoform-specific and negatively feeds back on the short-term response. Furthermore, long-term regulation involves transcription and translation of the respective α-isoform, whereas short-term regulation involves the translocation of the available α-isoform to the plasma membrane. © 2014 S. Karger AG, Basel.
Mechanisms of Isoform-Specific Na/K Pump Regulation by Short- and Long-Term Adrenergic Activation in Rat Ventricular Myocytes

Directory of Open Access Journals (Sweden)

Jian Yin

2014-05-01

Full Text Available Background: Many stressful conditions, including cardiovascular diseases, induce long-term elevations in circulating catecholamines, thereby leading to changes of the Na/K pump and thus affecting myocardial functions. However, only short-term adrenergic regulation of the Na/K pump has been reported. The present study is the first investigation of long-term adrenergic regulation of the Na/K pump and the potential mechanism. Methods: After acutely isolated Sprague-Dawley rat myocytes were incubated with noradrenaline or isoprenaline for 24 h, Na/K pump high- (IPH and low-affinity current (IPL, α-isoform mRNA, and α-isoform protein were examined using patch-clamp, RT-PCR, and Western blotting techniques, respectively. Results: After the short-term incubation, isoprenaline reduced the IPL through a PKA-dependent pathway that involves α1-isoform translocation from the membrane to early endosomes, and noradrenaline increased the IPH through a PKC-dependent pathway that involves α2-isoform translocation from late endosomes to the membrane. After long-term incubation, isoprenaline increased the IPL, α1-isoform mRNA, and α1-isoform protein, and noradrenaline reduced the IPH, α2-isoform mRNA, and α1-isoform protein through a PKA-or PKC-dependent pathway, respectively. Conclusions: These results suggest that long-term adrenergic Na/K pump regulation is isoform-specific and negatively feeds back on the short-term response. Furthermore, long-term regulation involves transcription and translation of the respective α-isoform, whereas short-term regulation involves the translocation of the available α-isoform to the plasma membrane.
Adsorption pump for helium pumping out

International Nuclear Information System (INIS)

Donde, A.L.; Semenenko, Yu.E.

1981-01-01

Adsorption pump with adsorbent cooling by liquid helium is described. Shuttered shield protecting adsorbent against radiation is cooled with evaporating helium passing along the coil positioned on the shield. The pump is also equipped with primed cylindrical shield, cooled with liquid nitrogen. The nitrogen shield has in the lower part the shuttered shield, on the pump casing there is a valve used for pump pre-burning, and valves for connection to recipient as well. Pumping- out rates are presented at different pressures and temperatures of adsorbent. The pumping-out rate according to air at absorbent cooling with liquid nitrogen constituted 5x10 -4 Pa-3000 l/s, at 2x10 -2 Pa-630 l/s. During the absorbent cooling with liquid hydrogen the pumping-out rate according to air was at 4x10 -4 Pa-580 l/s, at 2x10 -3 Pa-680 l/s, according to hydrogen - at 8x10 -5 Pa-2500 l/s, at 5x10 -3 Pa-4200 l/s. During adsorbent cooling with liquid helium the rate of pumping-out according to hydrogen at 3x10 5 Pa-2400% l/s, at 6x10 3 Pa-1200 l/s, and according to helium at 3.5x10 -5 Pa-2800 l/s, at 4x10 -3 Pa-1150 l/s. The limit vacuum is equal to 1x10 -7 Pa. The volume of the vessel with liquid helium is equal to 3.5 l. Helium consumption is 80 cm 3 /h. Consumption of liquid nitrogen from the shield is 400 cm 3 /h. The limit pressure in the pump is obtained after forevacuum pumping-out (adsorbent regeneration) at 300 K temperature. The pump is made of copper. The pump height together with primed tubes is 800 mm diameter-380 mm [ru

Some links on this page may take you to non-federal websites. Their policies may differ from this site.