Expanding the View of Proton Pumping in Cytochrome c Oxidase through Computer Simulation

PubMed Central

Peng, Yuxing; Voth, Gregory A.

2011-01-01

In cytochrome c oxidase (CcO), a redox-driven proton pump, protons are transported by the Grotthuss shuttling via hydrogen-bonded water molecules and protonatable residues. Proton transport through the D-pathway is a complicated process that is highly sensitive to alterations in the amino acids or the solvation structure in the channel, both of which can inhibit proton pumping and enzymatic activity. Simulations of proton transport in the hydrophobic cavity showed a clear redox state dependence. To study the mechanism of proton pumping in CcO, multi-state empirical valence bond (MS-EVB) simulations have been conducted, focusing on the proton transport through the D-pathway and the hydrophobic cavity next to the binuclear center. The hydration structures, transport pathways, effects of residues, and free energy surfaces of proton transport were revealed in these MS-EVB simulations. The mechanistic insight gained from them is herein reviewed and placed in context for future studies. PMID:22178790

Biological proton pumping in an oscillating electric field

PubMed Central

Kim, Young C.; Furchtgott, Leon A.; Hummer, Gerhard

2010-01-01

Time-dependent external perturbations provide powerful probes of the function of molecular machines. Here we study biological proton pumping in an oscillating electric field. The protein cytochrome c oxidase is the main energy transducer in aerobic life, converting chemical energy into an electric potential by pumping protons across a membrane. With the help of master-equation descriptions that recover the key thermodynamic and kinetic properties of this biological “fuel cell,” we show that the proton pumping efficiency and the electronic currents in steady state both depend significantly and distinctly on the frequency and amplitude of the applied field, allowing us to distinguish between different microscopic mechanisms of the machine. A spectral analysis reveals dominant kinetic modes that show reaction steps consistent with an electron-gated pumping mechanism. PMID:20366348

Piston-assisted proton pumping in Complex I of mitochondria membranes

NASA Astrophysics Data System (ADS)

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.

A three-dimensional movie of structural changes in bacteriorhodopsin.

PubMed

Nango, Eriko; Royant, Antoine; Kubo, Minoru; Nakane, Takanori; Wickstrand, Cecilia; Kimura, Tetsunari; Tanaka, Tomoyuki; Tono, Kensuke; Song, Changyong; Tanaka, Rie; Arima, Toshi; Yamashita, Ayumi; Kobayashi, Jun; Hosaka, Toshiaki; Mizohata, Eiichi; Nogly, Przemyslaw; Sugahara, Michihiro; Nam, Daewoong; Nomura, Takashi; Shimamura, Tatsuro; Im, Dohyun; Fujiwara, Takaaki; Yamanaka, Yasuaki; Jeon, Byeonghyun; Nishizawa, Tomohiro; Oda, Kazumasa; Fukuda, Masahiro; Andersson, Rebecka; Båth, Petra; Dods, Robert; Davidsson, Jan; Matsuoka, Shigeru; Kawatake, Satoshi; Murata, Michio; Nureki, Osamu; Owada, Shigeki; Kameshima, Takashi; Hatsui, Takaki; Joti, Yasumasa; Schertler, Gebhard; Yabashi, Makina; Bondar, Ana-Nicoleta; Standfuss, Jörg; Neutze, Richard; Iwata, So

2016-12-23

Bacteriorhodopsin (bR) is a light-driven proton pump and a model membrane transport protein. We used time-resolved serial femtosecond crystallography at an x-ray free electron laser to visualize conformational changes in bR from nanoseconds to milliseconds following photoactivation. An initially twisted retinal chromophore displaces a conserved tryptophan residue of transmembrane helix F on the cytoplasmic side of the protein while dislodging a key water molecule on the extracellular side. The resulting cascade of structural changes throughout the protein shows how motions are choreographed as bR transports protons uphill against a transmembrane concentration gradient. Copyright © 2016, American Association for the Advancement of Science.

Light energy conservation processes in Halobacterium halobium cells

NASA Technical Reports Server (NTRS)

Bogomolni, R. A.

1977-01-01

Proton pumping driven by light or by respiration generates an electrochemical potential difference across the membrane in Halobacterium halobium. The pH changes induced by light or by respiration in cell suspensions are complicated by proton flows associated with the functioning of the cellular energy transducers. A proton-per-ATP ratio of about 3 is calculated from simultaneous measurements of phosphorylation and the proton inflow. This value is compatible with the chemiosmotic coupling hypothesis. The time course of the light-induced changes in membrane potential indicates that light-driven pumping increases a dark pre-existing potential of about 130 mV only by a small amount (20 to 30 mV). The complex kinetic features of the membrane potential changes do not closely follow those of the pH changes, which suggests that flows of ions other than protons are involved. A qualitative model consistent with the available data is presented.

Structural basis for energy transduction by respiratory alternative complex III.

PubMed

Sousa, Joana S; Calisto, Filipa; Langer, Julian D; Mills, Deryck J; Refojo, Patrícia N; Teixeira, Miguel; Kühlbrandt, Werner; Vonck, Janet; Pereira, Manuela M

2018-04-30

Electron transfer in respiratory chains generates the electrochemical potential that serves as energy source for the cell. Prokaryotes can use a wide range of electron donors and acceptors and may have alternative complexes performing the same catalytic reactions as the mitochondrial complexes. This is the case for the alternative complex III (ACIII), a quinol:cytochrome c/HiPIP oxidoreductase. In order to understand the catalytic mechanism of this respiratory enzyme, we determined the structure of ACIII from Rhodothermus marinus at 3.9 Å resolution by single-particle cryo-electron microscopy. ACIII presents a so-far unique structure, for which we establish the arrangement of the cofactors (four iron-sulfur clusters and six c-type hemes) and propose the location of the quinol-binding site and the presence of two putative proton pathways in the membrane. Altogether, this structure provides insights into a mechanism for energy transduction and introduces ACIII as a redox-driven proton pump.

Flexibility within the rotor and stators of the vacuolar H+-ATPase.

PubMed

Song, Chun Feng; Papachristos, Kostas; Rawson, Shaun; Huss, Markus; Wieczorek, Helmut; Paci, Emanuele; Trinick, John; Harrison, Michael A; Muench, Stephen P

2013-01-01

The V-ATPase is a membrane-bound protein complex which pumps protons across the membrane to generate a large proton motive force through the coupling of an ATP-driven 3-stroke rotary motor (V1) to a multistroke proton pump (Vo). This is done with near 100% efficiency, which is achieved in part by flexibility within the central rotor axle and stator connections, allowing the system to flex to minimise the free energy loss of conformational changes during catalysis. We have used electron microscopy to reveal distinctive bending along the V-ATPase complex, leading to angular displacement of the V1 domain relative to the Vo domain to a maximum of ~30°. This has been complemented by elastic network normal mode analysis that shows both flexing and twisting with the compliance being located in the rotor axle, stator filaments, or both. This study provides direct evidence of flexibility within the V-ATPase and by implication in related rotary ATPases, a feature predicted to be important for regulation and their high energetic efficiencies.

Modeling the detailed kinetics of mitochondrial cytochrome c oxidase: Catalytic mechanism and nitric oxide inhibition

PubMed Central

Pannala, Venkat R.; Camara, Amadou K. S.

2016-01-01

Cytochrome c oxidase (CcO) catalyzes the exothermic reduction of O2 to H2O by using electrons from cytochrome c, and hence plays a crucial role in ATP production. Although details on the enzyme structure and redox centers involved in O2 reduction have been known, there still remains a considerable ambiguity on its mechanism of action, e.g., the number of sequential electrons donated to O2 in each catalytic step, the sites of protonation and proton pumping, and nitric oxide (NO) inhibition mechanism. In this work, we developed a thermodynamically constrained mechanistic mathematical model for the catalytic action of CcO based on available kinetic data. The model considers a minimal number of redox centers on CcO and couples electron transfer and proton pumping driven by proton motive force (PMF), and accounts for the inhibitory effects of NO on the reaction kinetics. The model is able to fit well all the available kinetic data under diverse experimental conditions with a physiologically realistic unique parameter set. The model predictions show that: 1) the apparent Km of O2 varies considerably and increases from fully reduced to fully oxidized cytochrome c depending on pH and the energy state of mitochondria, and 2) the intermediate enzyme states depend on pH and cytochrome c redox fraction and play a central role in coupling mitochondrial respiration to PMF. The developed CcO model can easily be integrated into existing mitochondrial bioenergetics models to understand the role of the enzyme in controlling oxidative phosphorylation in normal and disease conditions. PMID:27633738

Time-resolved generation of membrane potential by ba3 cytochrome c oxidase from Thermus thermophilus coupled to single electron injection into the O and OH states.

PubMed

Siletsky, Sergey A; Belevich, Ilya; Belevich, Nikolai P; Soulimane, Tewfik; Wikström, Mårten

2017-11-01

Two electrogenic phases with characteristic times of ~14μs and ~290μs are resolved in the kinetics of membrane potential generation coupled to single-electron reduction of the oxidized "relaxed" O state of ba 3 oxidase from T. thermophilus (O→E transition). The rapid phase reflects electron redistribution between Cu A and heme b. The slow phase includes electron redistribution from both Cu A and heme b to heme a 3 , and electrogenic proton transfer coupled to reduction of heme a 3 . The distance of proton translocation corresponds to uptake of a proton from the inner water phase into the binuclear center where heme a 3 is reduced, but there is no proton pumping and no reduction of Cu B . Single-electron reduction of the oxidized "unrelaxed" state (O H →E H transition) is accompanied by electrogenic reduction of the heme b/heme a 3 pair by Cu A in a "fast" phase (~22μs) and transfer of protons in "middle" and "slow" electrogenic phases (~0.185ms and ~0.78ms) coupled to electron redistribution from the heme b/heme a 3 pair to the Cu B site. The "middle" and "slow" electrogenic phases seem to be associated with transfer of protons to the proton-loading site (PLS) of the proton pump, but when all injected electrons reach Cu B the electronic charge appears to be compensated by back-leakage of the protons from the PLS into the binuclear site. Thus proton pumping occurs only to the extent of ~0.1 H + /e - , probably due to the formed membrane potential in the experiment. Copyright © 2017 Elsevier B.V. All rights reserved.

Intrinsic uncoupling of mitochondrial proton pumps. 2. Modeling studies.

PubMed

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 pumping accompanies calcification in foraminifera.

PubMed

Toyofuku, Takashi; Matsuo, Miki Y; de Nooijer, Lennart Jan; Nagai, Yukiko; Kawada, Sachiko; Fujita, Kazuhiko; Reichart, Gert-Jan; Nomaki, Hidetaka; Tsuchiya, Masashi; Sakaguchi, Hide; Kitazato, Hiroshi

2017-01-27

Ongoing ocean acidification is widely reported to reduce the ability of calcifying marine organisms to produce their shells and skeletons. Whereas increased dissolution due to acidification is a largely inorganic process, strong organismal control over biomineralization influences calcification and hence complicates predicting the response of marine calcifyers. Here we show that calcification is driven by rapid transformation of bicarbonate into carbonate inside the cytoplasm, achieved by active outward proton pumping. Moreover, this proton flux is maintained over a wide range of pCO 2 levels. We furthermore show that a V-type H + ATPase is responsible for the proton flux and thereby calcification. External transformation of bicarbonate into CO 2 due to the proton pumping implies that biomineralization does not rely on availability of carbonate ions, but total dissolved CO 2 may not reduce calcification, thereby potentially maintaining the current global marine carbonate production.

Proton pumping accompanies calcification in foraminifera

NASA Astrophysics Data System (ADS)

Toyofuku, Takashi; Matsuo, Miki Y.; de Nooijer, Lennart Jan; Nagai, Yukiko; Kawada, Sachiko; Fujita, Kazuhiko; Reichart, Gert-Jan; Nomaki, Hidetaka; Tsuchiya, Masashi; Sakaguchi, Hide; Kitazato, Hiroshi

2017-01-01

Ongoing ocean acidification is widely reported to reduce the ability of calcifying marine organisms to produce their shells and skeletons. Whereas increased dissolution due to acidification is a largely inorganic process, strong organismal control over biomineralization influences calcification and hence complicates predicting the response of marine calcifyers. Here we show that calcification is driven by rapid transformation of bicarbonate into carbonate inside the cytoplasm, achieved by active outward proton pumping. Moreover, this proton flux is maintained over a wide range of pCO2 levels. We furthermore show that a V-type H+ ATPase is responsible for the proton flux and thereby calcification. External transformation of bicarbonate into CO2 due to the proton pumping implies that biomineralization does not rely on availability of carbonate ions, but total dissolved CO2 may not reduce calcification, thereby potentially maintaining the current global marine carbonate production.

Carbon Nanotube-Based Membrane for Light-Driven, Simultaneous Proton and Electron Transport

DOE PAGES

Pilgrim, Gregory A.; Amori, Amanda R.; Hou, Zhentao; ...

2016-12-07

Here we discuss the photon driven transport of protons and electrons over hundreds of microns through a membrane based on vertically aligned single walled carbon nanotubes (SWNTs). Electrons are photogenerated in colloidal CdSe quantum dots that have been noncovalently attached to the carbon nanotube membrane and can be delivered at potentials capable of reducing earth-abundant molecular catalysts that perform proton reduction. Proton transport is driven by the electron photocurrent and is shown to be faster through the SWNT based membrane than through the commercial polymer Nafion. Furthermore, the potential utility of SWNT membranes for solar water splitting applications is demonstratedmore » through their excellent proton and electron transport properties as well as their ability to interact with other components of water splitting systems, such as small molecule electron acceptors.« less

High V-PPase activity is beneficial under high salt loads, but detrimental without salinity.

PubMed

Graus, Dorothea; Konrad, Kai R; Bemm, Felix; Patir Nebioglu, Meliha Görkem; Lorey, Christian; Duscha, Kerstin; Güthoff, Tilman; Herrmann, Johannes; Ferjani, Ali; Cuin, Tracey Ann; Roelfsema, M Rob G; Schumacher, Karin; Neuhaus, H Ekkehard; Marten, Irene; Hedrich, Rainer

2018-06-25

The membrane-bound proton-pumping pyrophosphatase (V-PPase), together with the V-type H + -ATPase, generates the proton motive force that drives vacuolar membrane solute transport. Transgenic plants constitutively overexpressing V-PPases were shown to have improved salinity tolerance, but the relative impact of increasing PP i hydrolysis and proton-pumping functions has yet to be dissected. For a better understanding of the molecular processes underlying V-PPase-dependent salt tolerance, we transiently overexpressed the pyrophosphate-driven proton pump (NbVHP) in Nicotiana benthamiana leaves and studied its functional properties in relation to salt treatment by primarily using patch-clamp, impalement electrodes and pH imaging. NbVHP overexpression led to higher vacuolar proton currents and vacuolar acidification. After 3 d in salt-untreated conditions, V-PPase-overexpressing leaves showed a drop in photosynthetic capacity, plasma membrane depolarization and eventual leaf necrosis. Salt, however, rescued NbVHP-hyperactive cells from cell death. Furthermore, a salt-induced rise in V-PPase but not of V-ATPase pump currents was detected in nontransformed plants. The results indicate that under normal growth conditions, plants need to regulate the V-PPase pump activity to avoid hyperactivity and its negative feedback on cell viability. Nonetheless, V-PPase proton pump function becomes increasingly important under salt stress for generating the pH gradient necessary for vacuolar proton-coupled Na + sequestration. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Reaction pathways of photoexcited retinal in proteorhodopsin studied by pump-dump-probe spectroscopy.

PubMed

Rupenyan, Alisa; van Stokkum, Ivo H M; Arents, Jos C; van Grondelle, Rienk; Hellingwerf, Klaas J; Groot, Marie Louise

2009-12-17

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 of the retinal chromophore of pR, using dispersed ultrafast pump-dump-probe spectroscopy. The application of a pump pulse initiates the photocycle, and with an appropriately tuned dump pulse applied at a time delay after the dump, the molecules in the initial stages of the photochemical process can be de-excited and driven back to the ground state. In this way, we were able to resolve an intermediate on the electronic ground state that represents chromophores that are unsuccessful in isomerization. In particular, the fractions of molecules that undergo slow isomerization (20 ps) have a high probability to enter this state rather than the isomerized K-state. On the ground state reaction surface, return to the stable ground state conformation via a structural or vibrational relaxation occurs in 2-3 ps. Inclusion of this intermediate in the kinetic scheme led to more consistent spectra of the retinal-excited state, and to a more accurate estimation of the quantum yield of isomerization (Phi = 0.4 at pH 6).

Development of a Compact, Efficient Cooling Pump for Space Suit Life Support Systems

NASA Technical Reports Server (NTRS)

van Boeyen, Roger; Reeh, Jonathan; Trevino, Luis

2009-01-01

A compact, low-power electrochemically-driven fluid cooling pump is currently being developed by Lynntech, Inc. With no electric motor and minimal lightweight components, the pump is significantly lighter than conventional rotodynamic and displacement pumps. Reliability and robustness is achieved with the absence of rotating or moving components (apart from the bellows). By employing sulfonated polystyrene-based proton exchange membranes, rather than conventional Nafion membranes, a significant reduction in the actuator power consumption was demonstrated. Lynntech also demonstrated that these membranes possess the necessary mechanical strength, durability, and temperature range for long life space operation. The preliminary design for a Phase II prototype pump compares very favorably to the fluid cooling pumps currently used in space suit primary life support systems (PLSSs). Characteristics of the electrochemically-driven pump are described and the benefits of the technology as a replacement for electric motor pumps in mechanically pumped single-phase fluid loops is discussed.

The Mg2+-containing Water Cluster of Mammalian Cytochrome c Oxidase Collects Four Pumping Proton Equivalents in Each Catalytic Cycle*

PubMed Central

Yano, Naomine; Muramoto, Kazumasa; Shimada, Atsuhiro; Takemura, Shuhei; Baba, Junpei; Fujisawa, Hidenori; Mochizuki, Masao; Shinzawa-Itoh, Kyoko; Yamashita, Eiki; Tsukihara, Tomitake; Yoshikawa, Shinya

2016-01-01

Bovine heart cytochrome c oxidase (CcO) pumps four proton equivalents per catalytic cycle through the H-pathway, a proton-conducting pathway, which includes a hydrogen bond network and a water channel operating in tandem. Protons are transferred by H3O+ through the water channel from the N-side into the hydrogen bond network, where they are pumped to the P-side by electrostatic repulsion between protons and net positive charges created at heme a as a result of electron donation to O2 bound to heme a3. To block backward proton movement, the water channel remains closed after O2 binding until the sequential four-proton pumping process is complete. Thus, the hydrogen bond network must collect four proton equivalents before O2 binding. However, a region with the capacity to accept four proton equivalents was not discernable in the x-ray structures of the hydrogen bond network. The present x-ray structures of oxidized/reduced bovine CcO are improved from 1.8/1.9 to 1.5/1.6 Å resolution, increasing the structural information by 1.7/1.6 times and revealing that a large water cluster, which includes a Mg2+ ion, is linked to the H-pathway. The cluster contains enough proton acceptor groups to retain four proton equivalents. The redox-coupled x-ray structural changes in Glu198, which bridges the Mg2+ and CuA (the initial electron acceptor from cytochrome c) sites, suggest that the CuA-Glu198-Mg2+ system drives redox-coupled transfer of protons pooled in the water cluster to the H-pathway. Thus, these x-ray structures indicate that the Mg2+-containing water cluster is the crucial structural element providing the effective proton pumping in bovine CcO. PMID:27605664

The Mg2+-containing Water Cluster of Mammalian Cytochrome c Oxidase Collects Four Pumping Proton Equivalents in Each Catalytic Cycle.

PubMed

Yano, Naomine; Muramoto, Kazumasa; Shimada, Atsuhiro; Takemura, Shuhei; Baba, Junpei; Fujisawa, Hidenori; Mochizuki, Masao; Shinzawa-Itoh, Kyoko; Yamashita, Eiki; Tsukihara, Tomitake; Yoshikawa, Shinya

2016-11-11

Bovine heart cytochrome c oxidase (CcO) pumps four proton equivalents per catalytic cycle through the H-pathway, a proton-conducting pathway, which includes a hydrogen bond network and a water channel operating in tandem. Protons are transferred by H 3 O + through the water channel from the N-side into the hydrogen bond network, where they are pumped to the P-side by electrostatic repulsion between protons and net positive charges created at heme a as a result of electron donation to O 2 bound to heme a 3 To block backward proton movement, the water channel remains closed after O 2 binding until the sequential four-proton pumping process is complete. Thus, the hydrogen bond network must collect four proton equivalents before O 2 binding. However, a region with the capacity to accept four proton equivalents was not discernable in the x-ray structures of the hydrogen bond network. The present x-ray structures of oxidized/reduced bovine CcO are improved from 1.8/1.9 to 1.5/1.6 Å resolution, increasing the structural information by 1.7/1.6 times and revealing that a large water cluster, which includes a Mg 2+ ion, is linked to the H-pathway. The cluster contains enough proton acceptor groups to retain four proton equivalents. The redox-coupled x-ray structural changes in Glu 198 , which bridges the Mg 2+ and Cu A (the initial electron acceptor from cytochrome c) sites, suggest that the Cu A -Glu 198 -Mg 2+ system drives redox-coupled transfer of protons pooled in the water cluster to the H-pathway. Thus, these x-ray structures indicate that the Mg 2+ -containing water cluster is the crucial structural element providing the effective proton pumping in bovine CcO. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Potential of proton-pumping rhodopsins: engineering photosystems into microorganisms.

PubMed

Claassens, Nico J; Volpers, Michael; dos Santos, Vitor A P Martins; van der Oost, John; de Vos, Willem M

2013-11-01

A wide range of proton-pumping rhodopsins (PPRs) have been discovered in recent years. Using a synthetic biology approach, PPR photosystems with different features can be easily introduced in nonphotosynthetic microbial hosts. PPRs can provide hosts with the ability to harvest light and drive the sustainable production of biochemicals or biofuels. PPRs use light energy to generate an outward proton flux, and the resulting proton motive force can subsequently power cellular processes. Recently, the introduction of PPRs in microbial production hosts has successfully led to light-driven biotechnological conversions. In this review, we discuss relevant features of natural PPRs, evaluate reported biotechnological applications of microbial production hosts equipped with PPRs, and provide an outlook on future developments. Copyright © 2013 Elsevier Ltd. All rights reserved.

Crystal structure of Escherichia coli-expressed Haloarcula marismortui bacteriorhodopsin I in the trimeric form.

PubMed

Shevchenko, Vitaly; Gushchin, Ivan; Polovinkin, Vitaly; Round, Ekaterina; Borshchevskiy, Valentin; Utrobin, Petr; Popov, Alexander; Balandin, Taras; Büldt, Georg; Gordeliy, Valentin

2014-01-01

Bacteriorhodopsins are a large family of seven-helical transmembrane proteins that function as light-driven proton pumps. Here, we present the crystal structure of a new member of the family, Haloarcula marismortui bacteriorhodopsin I (HmBRI) D94N mutant, at the resolution of 2.5 Å. While the HmBRI retinal-binding pocket and proton donor site are similar to those of other archaeal proton pumps, its proton release region is extended and contains additional water molecules. The protein's fold is reinforced by three novel inter-helical hydrogen bonds, two of which result from double substitutions relative to Halobacterium salinarum bacteriorhodopsin and other similar proteins. Despite the expression in Escherichia coli and consequent absence of native lipids, the protein assembles as a trimer in crystals. The unique extended loop between the helices D and E of HmBRI makes contacts with the adjacent protomer and appears to stabilize the interface. Many lipidic hydrophobic tail groups are discernible in the membrane region, and their positions are similar to those of archaeal isoprenoid lipids in the crystals of other proton pumps, isolated from native or native-like sources. All these features might explain the HmBRI properties and establish the protein as a novel model for the microbial rhodopsin proton pumping studies.

The nitric-oxide reductase from Paracoccus denitrificans uses a single specific proton pathway.

PubMed

ter Beek, Josy; Krause, Nils; Reimann, Joachim; Lachmann, Peter; Ädelroth, Pia

2013-10-18

The NO reductase from Paracoccus denitrificans reduces NO to N2O (2NO + 2H(+) + 2e(-) → N2O + H2O) with electrons donated by periplasmic cytochrome c (cytochrome c-dependent NO reductase; cNOR). cNORs are members of the heme-copper oxidase superfamily of integral membrane proteins, comprising the O2-reducing, proton-pumping respiratory enzymes. In contrast, although NO reduction is as exergonic as O2 reduction, there are no protons pumped in cNOR, and in addition, protons needed for NO reduction are derived from the periplasmic solution (no contribution to the electrochemical gradient is made). cNOR thus only needs to transport protons from the periplasm into the active site without the requirement to control the timing of opening and closing (gating) of proton pathways as is needed in a proton pump. Based on the crystal structure of a closely related cNOR and molecular dynamics simulations, several proton transfer pathways were suggested, and in principle, these could all be functional. In this work, we show that residues in one of the suggested pathways (denoted pathway 1) are sensitive to site-directed mutation, whereas residues in the other proposed pathways (pathways 2 and 3) could be exchanged without severe effects on turnover activity with either NO or O2. We further show that electron transfer during single-turnover reduction of O2 is limited by proton transfer and can thus be used to study alterations in proton transfer rates. The exchange of residues along pathway 1 showed specific slowing of this proton-coupled electron transfer as well as changes in its pH dependence. Our results indicate that only pathway 1 is used to transfer protons in cNOR.

Crystal structure of the plasma membrane proton pump.

PubMed

Pedersen, Bjørn P; Buch-Pedersen, Morten J; Morth, J Preben; Palmgren, Michael G; Nissen, Poul

2007-12-13

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: H+-ATPase (the proton pump) in plants and fungi, and Na+,K+-ATPase (the sodium-potassium pump) in animals. The name P-type derives from the fact that these proteins exploit a phosphorylated reaction cycle intermediate of ATP hydrolysis. The plasma membrane proton pumps belong to the type III P-type ATPase subfamily, whereas Na+,K+-ATPase and Ca2+-ATPase are type II. Electron microscopy has revealed the overall shape of proton pumps, 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 the functional unit of ATP-coupled proton transport across the plasma membrane, and the structure is locked in a functional state not previously observed in P-type ATPases. The transmembrane domain reveals a large cavity, which is likely to be filled with water, located near the middle of the membrane plane where it is lined by conserved hydrophilic and charged residues. Proton transport against a high membrane potential is readily explained by this structural arrangement.

Enhanced proton acceleration in an applied longitudinal magnetic field

DOE PAGES

Arefiev, A.; Toncian, T.; Fiksel, G.

2016-10-31

Using two-dimensional particle-in-cell simulations, we examine how an externally applied strong magnetic field impacts proton acceleration in laser-irradiated solid-density targets. We find that a kT-level external magnetic field can sufficiently inhibit transverse transport of hot electrons in a flat laser-irradiated target. While the electron heating by the laser remains mostly unaffected, the reduced electron transport during proton acceleration leads to an enhancement of maximum proton energies and the overall number of energetic protons. The resulting proton beam is much better collimated compared to a beam generated without applying a kT-level magnetic field. A factor of three enhancement of the lasermore » energy conversion efficiency into multi-MeV protons is another effect of the magnetic field. The required kT-level magnetic fields are becoming feasible due to a significant progress that has been made in generating magnetic fields with laser-driven coils using ns-long laser pulses. The possibility of improving characteristics of laser-driven proton beams using such fields is a strong motivation for further development of laser-driven magnetic field capabilities.« less

Enhanced proton acceleration in an applied longitudinal magnetic field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arefiev, A.; Toncian, T.; Fiksel, G.

Using two-dimensional particle-in-cell simulations, we examine how an externally applied strong magnetic field impacts proton acceleration in laser-irradiated solid-density targets. We find that a kT-level external magnetic field can sufficiently inhibit transverse transport of hot electrons in a flat laser-irradiated target. While the electron heating by the laser remains mostly unaffected, the reduced electron transport during proton acceleration leads to an enhancement of maximum proton energies and the overall number of energetic protons. The resulting proton beam is much better collimated compared to a beam generated without applying a kT-level magnetic field. A factor of three enhancement of the lasermore » energy conversion efficiency into multi-MeV protons is another effect of the magnetic field. The required kT-level magnetic fields are becoming feasible due to a significant progress that has been made in generating magnetic fields with laser-driven coils using ns-long laser pulses. The possibility of improving characteristics of laser-driven proton beams using such fields is a strong motivation for further development of laser-driven magnetic field capabilities.« less

Lipidic cubic phase serial millisecond crystallography using synchrotron radiation

PubMed Central

Nogly, Przemyslaw; James, Daniel; Wang, Dingjie; White, Thomas A.; Zatsepin, Nadia; Shilova, Anastasya; Nelson, Garrett; Liu, Haiguang; Johansson, Linda; Heymann, Michael; Jaeger, Kathrin; Metz, Markus; Wickstrand, Cecilia; Wu, Wenting; Båth, Petra; Berntsen, Peter; Oberthuer, Dominik; Panneels, Valerie; Cherezov, Vadim; Chapman, Henry; Schertler, Gebhard; Neutze, Richard; Spence, John; Moraes, Isabel; Burghammer, Manfred; Standfuss, Joerg; Weierstall, Uwe

2015-01-01

Lipidic cubic phases (LCPs) have emerged as successful matrixes for the crystallization of membrane proteins. Moreover, the viscous LCP also provides a highly effective delivery medium for serial femtosecond crystallography (SFX) at X-ray free-electron lasers (XFELs). Here, the adaptation of this technology to perform serial millisecond crystallography (SMX) at more widely available synchrotron microfocus beamlines is described. Compared with conventional microcrystallography, LCP-SMX eliminates the need for difficult handling of individual crystals and allows for data collection at room temperature. The technology is demonstrated by solving a structure of the light-driven proton-pump bacteriorhodopsin (bR) at a resolution of 2.4 Å. The room-temperature structure of bR is very similar to previous cryogenic structures but shows small yet distinct differences in the retinal ligand and proton-transfer pathway. PMID:25866654

Proton transfer mediated by the vibronic coupling in oxygen core ionized states of glyoxalmonoxime studied by infrared-X-ray pump-probe spectroscopy.

PubMed

Felicíssimo, V C; Guimarães, F F; Cesar, A; Gel'mukhanov, F; Agren, H

2006-11-30

The theory of IR-X-ray pump-probe spectroscopy beyond the Born-Oppenheimer approximation is developed and applied to the study of the dynamics of intramolecular proton transfer in glyoxalmonoxime leading to the formation of the tautomer 2-nitrosoethenol. Due to the IR pump pulses the molecule gains sufficient energy to promote a proton to a weakly bound well. A femtosecond X-ray pulse snapshots the wave packet route and, hence, the dynamics of the proton transfer. The glyoxalmonoxime molecule contains two chemically nonequivalent oxygen atoms that possess distinct roles in the hydrogen bond, a hydrogen donor and an acceptor. Core ionizations of these form two intersecting core-ionized states, the vibronic coupling between which along the OH stretching mode partially delocalizes the core hole, resulting in a hopping of the core hole from one site to another. This, in turn, affects the dynamics of the proton transfer in the core-ionized state. The quantum dynamical simulations of X-ray photoelectron spectra of glyoxalmonoxime driven by strong IR pulses demonstrate the general applicability of the technique for studies of intramolecular proton transfer in systems with vibronic coupling.

High-quality electron beam generation in a proton-driven hollow plasma wakefield accelerator

NASA Astrophysics Data System (ADS)

Li, Y.; Xia, G.; Lotov, K. V.; Sosedkin, A. P.; Hanahoe, K.; Mete-Apsimon, O.

2017-10-01

Simulations of proton-driven plasma wakefield accelerators have demonstrated substantially higher accelerating gradients compared to conventional accelerators and the viability of accelerating electrons to the energy frontier in a single plasma stage. However, due to the strong intrinsic transverse fields varying both radially and in time, the witness beam quality is still far from suitable for practical application in future colliders. Here we demonstrate the efficient acceleration of electrons in proton-driven wakefields in a hollow plasma channel. In this regime, the witness bunch is positioned in the region with a strong accelerating field, free from plasma electrons and ions. We show that the electron beam carrying the charge of about 10% of 1 TeV proton driver charge can be accelerated to 0.6 TeV with a preserved normalized emittance in a single channel of 700 m. This high-quality and high-charge beam may pave the way for the development of future plasma-based energy frontier colliders.

Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography

DOE PAGES

Nogly, Przemyslaw; Panneels, Valerie; Nelson, Garrett; ...

2016-08-22

Serial femtosecond crystallography (SFX) using X-ray free-electron laser sources is an emerging method with considerable potential for time-resolved pump-probe experiments. Here we present a lipidic cubic phase SFX structure of the light-driven proton pump bacteriorhodopsin (bR) to 2.3 Å resolution and a method to investigate protein dynamics with modest sample requirement. Time-resolved SFX (TR-SFX) with a pump-probe delay of 1 ms yields difference Fourier maps compatible with the dark to M state transition of bR. Importantly, the method is very sample efficient and reduces sample consumption to about 1 mg per collected time point. Accumulation of M intermediate within themore » crystal lattice is confirmed by time-resolved visible absorption spectroscopy. Furthermore, this study provides an important step towards characterizing the complete photocycle dynamics of retinal proteins and demonstrates the feasibility of a sample efficient viscous medium jet for TR-SFX.« less

Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nogly, Przemyslaw; Panneels, Valerie; Nelson, Garrett

Serial femtosecond crystallography (SFX) using X-ray free-electron laser sources is an emerging method with considerable potential for time-resolved pump-probe experiments. Here we present a lipidic cubic phase SFX structure of the light-driven proton pump bacteriorhodopsin (bR) to 2.3 Å resolution and a method to investigate protein dynamics with modest sample requirement. Time-resolved SFX (TR-SFX) with a pump-probe delay of 1 ms yields difference Fourier maps compatible with the dark to M state transition of bR. Importantly, the method is very sample efficient and reduces sample consumption to about 1 mg per collected time point. Accumulation of M intermediate within themore » crystal lattice is confirmed by time-resolved visible absorption spectroscopy. Furthermore, this study provides an important step towards characterizing the complete photocycle dynamics of retinal proteins and demonstrates the feasibility of a sample efficient viscous medium jet for TR-SFX.« less

Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography

PubMed Central

Nogly, Przemyslaw; Panneels, Valerie; Nelson, Garrett; Gati, Cornelius; Kimura, Tetsunari; Milne, Christopher; Milathianaki, Despina; Kubo, Minoru; Wu, Wenting; Conrad, Chelsie; Coe, Jesse; Bean, Richard; Zhao, Yun; Båth, Petra; Dods, Robert; Harimoorthy, Rajiv; Beyerlein, Kenneth R.; Rheinberger, Jan; James, Daniel; DePonte, Daniel; Li, Chufeng; Sala, Leonardo; Williams, Garth J.; Hunter, Mark S.; Koglin, Jason E.; Berntsen, Peter; Nango, Eriko; Iwata, So; Chapman, Henry N.; Fromme, Petra; Frank, Matthias; Abela, Rafael; Boutet, Sébastien; Barty, Anton; White, Thomas A.; Weierstall, Uwe; Spence, John; Neutze, Richard; Schertler, Gebhard; Standfuss, Jörg

2016-01-01

Serial femtosecond crystallography (SFX) using X-ray free-electron laser sources is an emerging method with considerable potential for time-resolved pump-probe experiments. Here we present a lipidic cubic phase SFX structure of the light-driven proton pump bacteriorhodopsin (bR) to 2.3 Å resolution and a method to investigate protein dynamics with modest sample requirement. Time-resolved SFX (TR-SFX) with a pump-probe delay of 1 ms yields difference Fourier maps compatible with the dark to M state transition of bR. Importantly, the method is very sample efficient and reduces sample consumption to about 1 mg per collected time point. Accumulation of M intermediate within the crystal lattice is confirmed by time-resolved visible absorption spectroscopy. This study provides an important step towards characterizing the complete photocycle dynamics of retinal proteins and demonstrates the feasibility of a sample efficient viscous medium jet for TR-SFX. PMID:27545823

Cyanobacterial Light-Driven Proton Pump, Gloeobacter Rhodopsin: Complementarity between Rhodopsin-Based Energy Production and Photosynthesis

PubMed Central

Choi, Ah Reum; Shi, Lichi; Brown, Leonid S.; Jung, Kwang-Hwan

2014-01-01

A homologue of type I rhodopsin was found in the unicellular Gloeobacter violaceus PCC7421, which is believed to be primitive because of the lack of thylakoids and peculiar morphology of phycobilisomes. The Gloeobacter rhodopsin (GR) gene encodes a polypeptide of 298 amino acids. This gene is localized alone in the genome unlike cyanobacterium Anabaena opsin, which is clustered together with 14 kDa transducer gene. Amino acid sequence comparison of GR with other type I rhodopsin shows several conserved residues important for retinal binding and H+ pumping. In this study, the gene was expressed in Escherichia coli and bound all-trans retinal to form a pigment (λmax  = 544 nm at pH 7). The pKa of proton acceptor (Asp121) for the Schiff base, is approximately 5.9, so GR can translocate H+ under physiological conditions (pH 7.4). In order to prove the functional activity in the cell, pumping activity was measured in the sphaeroplast membranes of E. coli and one of Gloeobacter whole cell. The efficient proton pumping and rapid photocycle of GR strongly suggests that Gloeobacter rhodopsin functions as a proton pumping in its natural environment, probably compensating the shortage of energy generated by chlorophyll-based photosynthesis without thylakoids. PMID:25347537

Properties of the anion-binding site of pharaonis Halorhodopsin studied by ultrafast pump-probe spectroscopy and low-temperature FTIR spectroscopy.

PubMed

Nakashima, Keisuke; Nakamura, Takumi; Takeuchi, Satoshi; Shibata, Mikihiro; Demura, Makoto; Tahara, Tahei; Kandori, Hideki

2009-06-18

Halorhodopsin (HR) is a light-driven chloride pump. Cl(-) is bound in the Schiff base region of the retinal chromophore, and unidirectional Cl(-) transport is probably enforced by the specific hydrogen-bonding interaction with the protonated Schiff base and internal water molecules. It is known that HR from Natronobacterium pharaonis (pHR) also pumps NO(3)(-) with similar efficiency, suggesting that NO(3)(-) binds to the Cl(-)-binding site. In the present study, we investigated the properties of the anion-binding site by means of ultrafast pump-probe spectroscopy and low-temperature FTIR spectroscopy. The obtained data were surprisingly similar between pHR-NO(3)(-) and pHR-Cl(-), even though the shapes and sizes of the two anions are quite different. Femtosecond pump-probe spectroscopy showed very similar excited-state dynamics between pHR-NO(3)(-) and pHR-Cl(-). Low-temperature FTIR spectroscopy of unlabeled and [zeta-(15)N]Lys-labeled pHR revealed almost identical hydrogen-bonding strengths of the protonated retinal Schiff base between pHR-NO(3)(-) and pHR-Cl(-), which is similarly strengthened after retinal isomerization. There were spectral variations for water stretching vibrations between pHR-NO(3)(-) and pHR-Cl(-), suggesting that the water molecules hydrate each anion. Nevertheless, the overall spectral features were similar for the two species. These observations strongly suggest that the anion-binding site has a flexible structure and that the interaction between retinal and the anions is weak, despite the presence of an electrostatic interaction. Such a flexible hydrogen-bonding network in the Schiff base region in HR appears to be in remarkable contrast to that in light-driven proton-pumping proteins.

Proton pump inhibitors are associated with accelerated development of cirrhosis, hepatic decompensation and hepatocellular carcinoma in noncirrhotic patients with chronic hepatitis C infection: results from ERCHIVES.

PubMed

Li, D K; Yan, P; Abou-Samra, A-B; Chung, R T; Butt, A A

2018-01-01

Proton pump inhibitors are among the most commonly prescribed medications in the United States. Their safety in cirrhosis has recently been questioned, but their overall effect on disease progression in noncirrhotic patients with chronic liver disease remains unclear. To determine the impact of proton pump inhibitors on the progression of liver disease in noncirrhotic patients with hepatitis C virus (HCV) infection. Using the electronically retrieved cohort of HCV-infected veterans (ERCHIVES) database, we identified all subjects who received HCV treatment and all incident cases of cirrhosis, hepatic decompensation and hepatocellular carcinoma. Proton pump inhibitor use was measured using cumulative defined daily dose. Multivariate Cox regression analysis was performed after adjusting univariate predictors of cirrhosis and various indications for proton pump inhibitor use. Among 11 526 eligible individuals, we found that exposure to proton pump inhibitors was independently associated with an increased risk of developing cirrhosis (hazard ratio [HR]: 1.32; 95% confidence interval: [1.17, 1.49]). This association remained robust to sensitivity analysis in which only patients who achieved sustained virologic response were analysed as well as analysis excluding those with alcohol abuse/dependence. Proton pump inhibitor exposure was also independently associated with an increased risk of hepatic decompensation (HR: 3.79 [2.58, 5.57]) and hepatocellular carcinoma (HR: 2.01 [1.50, 2.70]). In patients with chronic HCV infection, increasing proton pump inhibitor use is associated with a dose-dependent risk of progression of chronic liver disease to cirrhosis, as well as an increased risk of hepatic decompensation and hepatocellular carcinoma. © 2017 John Wiley & Sons Ltd.

Electrogenic steps of light-driven proton transport in ESR, a retinal protein from Exiguobacterium sibiricum.

PubMed

Siletsky, Sergey A; Mamedov, Mahir D; Lukashev, Evgeniy P; Balashov, Sergei P; Dolgikh, Dmitriy A; Rubin, Andrei B; Kirpichnikov, Mikhail P; Petrovskaya, Lada E

2016-11-01

A retinal protein from Exiguobacterium sibiricum (ESR) functions as a light-driven proton pump. Unlike other proton pumps, it contains Lys96 instead of a usual carboxylic residue in the internal proton donor site. Nevertheless, the reprotonation of the Schiff base occurs fast, indicating that Lys96 facilitates proton transfer from the bulk. In this study we examined kinetics of light-induced transmembrane electrical potential difference, ΔΨ, generated in proteoliposomes reconstituted with ESR. We show that total magnitude of ΔΨ is comparable to that produced by bacteriorhodopsin but its kinetic components and their pH dependence are substantially different. The results are in agreement with the earlier finding that proton uptake precedes reprotonation of the Schiff base in ESR, suggesting that Lys96 is unprotonated in the initial state and gains a proton transiently in the photocycle. The electrogenic phases and the photocycle transitions related to proton transfer from the bulk to the Schiff base are pH dependent. At neutral pH, they occur with τ 0.5ms and 4.5ms. At alkaline pH, the fast component ceases and Schiff base reprotonation slows. At pH8.4, a spectrally silent electrogenic component with τ 0.25ms is detected, which can be attributed to proton transfer from the bulk to Lys96. At pH5.1, the amplitude of ΔΨ decreases 10 fold, reflecting a decreased yield and rate of proton transfer, apparently from protonation of the acceptor (Asp85-His57 pair) in the initial state. The features of the photoelectric potential generation correlate with the ESR structure and proposed mechanism of proton transfer. Copyright © 2016 Elsevier B.V. All rights reserved.

A light-driven proton pump from Haloterrigena turkmenica: Functional expression in Escherichia coli membrane and coupling with a H{sup +} co-transporter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamo, Naoki; Hashiba, Tsuyoshi; Kikukawa, Takashi

2006-03-10

A gene encoding putative retinal protein was cloned from Haloterrigena turkmenica (JCM9743). The deduced amino acid sequence was most closely related to that of deltarhodopsin, which functions as a light-driven H{sup +} pump and was identified in a novel strain Haloterrigena sp. arg-4 (K. Ihara, T. Uemura, I. Katagiri, T. Kitajima-Ihara, Y. Sugiyama, Y. Kimura, Y. Mukohata, Evolution of the archaeal rhodopsins: Evolution rate changes by gene duplication and functional differentiation, J. Mol. Biol. 285 (1999) 163-174. GenBank Accession No. AB009620). Thus, we called the present protein H. turkmenica deltarhodopsin (HtdR) in this report. Differing from the Halobacterium salinarum bacteriorhodopsinmore » (bR), functional expression of HtdR was achieved in Escherichia coli membrane with a high yield of 10-15mg protein/L culture. The photocycle of purified HtdR was similar to that of bR. The photo-induced electrogenic proton pumping activity of HtdR was verified. We co-expressed both HtdR and EmrE, a proton-coupled multi-drug efflux transporter in E. coli, and the cells successfully extruded ethidium, a substrate of EmrE, on illumination.« less

Key parameters controlling the performance of catalytic motors.

PubMed

Esplandiu, Maria J; Afshar Farniya, Ali; Reguera, David

2016-03-28

The development of autonomous micro/nanomotors driven by self-generated chemical gradients is a topic of high interest given their potential impact in medicine and environmental remediation. Although impressive functionalities of these devices have been demonstrated, a detailed understanding of the propulsion mechanism is still lacking. In this work, we perform a comprehensive numerical analysis of the key parameters governing the actuation of bimetallic catalytic micropumps. We show that the fluid motion is driven by self-generated electro-osmosis where the electric field originates by a proton current rather than by a lateral charge asymmetry inside the double layer. Hence, the surface potential and the electric field are the key parameters for setting the pumping strength and directionality. The proton flux that generates the electric field stems from the proton gradient induced by the electrochemical reactions taken place at the pump. Surprisingly the electric field and consequently the fluid flow are mainly controlled by the ionic strength and not by the conductivity of the solution, as one could have expected. We have also analyzed the influence of the chemical fuel concentration, electrochemical reaction rates, and size of the metallic structures for an optimized pump performance. Our findings cast light on the complex chemomechanical actuation of catalytic motors and provide important clues for the search, design, and optimization of novel catalytic actuators.

Essential arginine in subunit a and aspartate in subunit c of FoF1 ATP synthase: effect of repositioning within helix 4 of subunit a and helix 2 of subunit c.

PubMed

Langemeyer, Lars; Engelbrecht, Siegfried

2007-07-01

FoF1 ATP synthase couples proton flow through the integral membrane portion Fo (ab2c10) to ATP-synthesis in the extrinsic F1-part ((alphabeta)3gammadeltaepsilon) (Escherichia coli nomenclature and stoichiometry). Coupling occurs by mechanical rotation of subunits c10gammaepsilon relative to (alphabeta)3deltaab2. Two residues were found to be essential for proton flow through ab2c10, namely Arg210 in subunit a (aR210) and Asp61 in subunits c (cD61). Their deletion abolishes proton flow, but "horizontal" repositioning, by anchoring them in adjacent transmembrane helices, restores function. Here, we investigated the effects of "vertical" repositioning aR210, cD61, or both by one helical turn towards the N- or C-termini of their original helices. Other than in the horizontal the vertical displacement changes the positions of the side chains within the depth of the membrane. Mutant aR210A/aN214R appeared to be short-circuited in that it supported proton conduction only through EF1-depleted EFo, but not in EFoEF1, nor ATP-driven proton pumping. Mutant cD61N/cM65D grew on succinate, retained the ability to synthesize ATP and supported passive proton conduction but apparently not ATP hydrolysis-driven proton pumping.

Reconstitution of halorhodopsin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong, T.

1989-11-01

Halobacterium halobium contains a family of retinal-bound proteins: bacteriorhodopsin (bR) which mediates phototrophic growth as a light-riven proton pump, halorhodopsin (hR) which is a light-driven chloride pump, and one or more sensory rhodopsins (sR) which mediate a phototactic response. Two-dimensional crystallization of halorhodopsin has been attempted though the reconstitution of purified halorhodopsin with purple membrane lipid for electron microscopy work. The first important step for crystallization is to get a homogeneous protein which is pure and not denatured. Homogeneous halorhodopsin has been obtained by a modification of existing purification methods. Some nice looking membrane patches which have the same densitymore » as purple membrane have been obtained. But unfortunately, they are not crystalline. The procedure of hR reconstitution is described in detail and some other strategies to induce the protein crystal in the reconstituted membrane are discussed in this dissertation. 76 refs., 20 figs., 6 tabs.« less

Conformational change during photocycle of bacteriorhodopsin and its proton-pumping mechanism.

PubMed

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 beam shaped by “particle lens” formed by laser-driven hot electrons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhai, S. H.; Shen, B. F., E-mail: bfshen@mail.shcnc.ac.cn, E-mail: wwpvin@hotmail.com, E-mail: yqgu@caep.cn; Wang, W. P., E-mail: bfshen@mail.shcnc.ac.cn, E-mail: wwpvin@hotmail.com, E-mail: yqgu@caep.cn

2016-05-23

Two-dimensional tailoring of a proton beam is realized by a “particle lens” in our experiment. A large quantity of electrons, generated by an intense femtosecond laser irradiating a polymer target, produces an electric field strong enough to change the trajectory and distribution of energetic protons flying through the electron area. The experiment shows that a strip pattern of the proton beam appears when hot electrons initially converge inside the plastic plate. Then the shape of the proton beam changes to a “fountain-like” pattern when these hot electrons diffuse after propagating a distance.

Tunneling induced electron transfer between separated protons

NASA Astrophysics Data System (ADS)

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.

Key parameters controlling the performance of catalytic motors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Esplandiu, Maria J.; Afshar Farniya, Ali; Reguera, David, E-mail: dreguera@ub.edu

2016-03-28

The development of autonomous micro/nanomotors driven by self-generated chemical gradients is a topic of high interest given their potential impact in medicine and environmental remediation. Although impressive functionalities of these devices have been demonstrated, a detailed understanding of the propulsion mechanism is still lacking. In this work, we perform a comprehensive numerical analysis of the key parameters governing the actuation of bimetallic catalytic micropumps. We show that the fluid motion is driven by self-generated electro-osmosis where the electric field originates by a proton current rather than by a lateral charge asymmetry inside the double layer. Hence, the surface potential andmore » the electric field are the key parameters for setting the pumping strength and directionality. The proton flux that generates the electric field stems from the proton gradient induced by the electrochemical reactions taken place at the pump. Surprisingly the electric field and consequently the fluid flow are mainly controlled by the ionic strength and not by the conductivity of the solution, as one could have expected. We have also analyzed the influence of the chemical fuel concentration, electrochemical reaction rates, and size of the metallic structures for an optimized pump performance. Our findings cast light on the complex chemomechanical actuation of catalytic motors and provide important clues for the search, design, and optimization of novel catalytic actuators.« less

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.

PubMed

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.

Ultrafast molecular processes mapped by femtosecond x-ray diffraction

NASA Astrophysics Data System (ADS)

Elsaesser, Thomas

2012-02-01

X-ray diffraction with a femtosecond time resolution allows for mapping photoinduced structural dynamics on the length scale of a chemical bond and in the time domain of atomic and molecular motion. In a pump-probe approach, a femtosecond excitation pulse induces structural changes which are probed by diffracting a femtosecond hard x-ray pulse from the excited sample. The transient angular positions and intensities of diffraction peaks give insight into the momentary atomic or molecular positions and into the distribution of electronic charge density. The simultaneous measurement of changes on different diffraction peaks is essential for determining atom positions and charge density maps with high accuracy. Recent progress in the generation of ultrashort hard x-ray pulses (Cu Kα, wavelength λ=0.154 nm) in laser-driven plasma sources has led to the implementation of the powder diffraction and the rotating crystal method with a time resolution of 100 fs. In this contribution, we report new results from powder diffraction studies of molecular materials. A first series of experiments gives evidence of a so far unknown concerted transfer of electrons and protons in ammonium sulfate [(NH4)2SO4], a centrosymmetric structure. Charge transfer from the sulfate groups results in the sub-100 fs generation of a confined electron channel along the c-axis of the unit cell which is stabilized by transferring protons from the adjacent ammonium groups into the channel. Time-dependent charge density maps display a periodic modulation of the channel's charge density by low-frequency lattice motions with a concerted electron and proton motion between the channel and the initial proton binding site. A second study addresses atomic rearrangements and charge dislocations in the non-centrosymmetric potassium dihydrogen phosphate [KH2PO4, KDP]. Photoexcitation generates coherent low-frequency motions along the LO and TO phonon coordinates, leaving the average atomic positions unchanged. The time-dependent maps of electron density demonstrate a concomitant oscillatory relocation of electronic charge with a spatial amplitude of the order of a chemical bond length, two orders of magnitude larger than the vibrational amplitudes. The coherent phonon motions drive the charge relocation, similar to a soft mode driven phase transition between the ferro- and paraelectric phase of KDP.

Nanoantioxidant-driven plasmon enhanced proton-coupled electron transfer

NASA Astrophysics Data System (ADS)

Sotiriou, Georgios A.; Blattmann, Christoph O.; Deligiannakis, Yiannis

2015-12-01

Proton-coupled electron transfer (PCET) reactions involve the transfer of a proton and an electron and play an important role in a number of chemical and biological processes. Here, we describe a novel phenomenon, plasmon-enhanced PCET, which is manifested using SiO2-coated Ag nanoparticles functionalized with gallic acid (GA), a natural antioxidant molecule that can perform PCET. These GA-functionalized nanoparticles show enhanced plasmonic response at near-IR wavelengths, due to particle agglomeration caused by the GA molecules. Near-IR laser irradiation induces strong local hot-spots on the SiO2-coated Ag nanoparticles, as evidenced by surface enhanced Raman scattering (SERS). This leads to plasmon energy transfer to the grafted GA molecules that lowers the GA-OH bond dissociation enthalpy by at least 2 kcal mol-1 and therefore facilitates PCET. The nanoparticle-driven plasmon-enhancement of PCET brings together the so far unrelated research domains of nanoplasmonics and electron/proton translocation with significant impact on applications based on interfacial electron/proton transfer.Proton-coupled electron transfer (PCET) reactions involve the transfer of a proton and an electron and play an important role in a number of chemical and biological processes. Here, we describe a novel phenomenon, plasmon-enhanced PCET, which is manifested using SiO2-coated Ag nanoparticles functionalized with gallic acid (GA), a natural antioxidant molecule that can perform PCET. These GA-functionalized nanoparticles show enhanced plasmonic response at near-IR wavelengths, due to particle agglomeration caused by the GA molecules. Near-IR laser irradiation induces strong local hot-spots on the SiO2-coated Ag nanoparticles, as evidenced by surface enhanced Raman scattering (SERS). This leads to plasmon energy transfer to the grafted GA molecules that lowers the GA-OH bond dissociation enthalpy by at least 2 kcal mol-1 and therefore facilitates PCET. The nanoparticle-driven plasmon-enhancement of PCET brings together the so far unrelated research domains of nanoplasmonics and electron/proton translocation with significant impact on applications based on interfacial electron/proton transfer. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04942c

The Contribution of Compressional Magnetic Pumping to the Energization of the Earth's Outer Electron Radiation Belt During High-Speed Stream-Driven Storms

NASA Astrophysics Data System (ADS)

Borovsky, Joseph E.; Horne, Richard B.; Meredith, Nigel P.

2017-12-01

Compressional magnetic pumping is an interaction between cyclic magnetic compressions and pitch angle scattering with the scattering acting as a catalyst to allow the cyclic compressions to energize particles. Compressional magnetic pumping of the outer electron radiation belt at geosynchronous orbit in the dayside magnetosphere is analyzed by means of computer simulations, wherein solar wind compressions of the dayside magnetosphere energize electrons with electron pitch angle scattering by chorus waves and by electromagnetic ion cyclotron (EMIC) waves. The magnetic pumping is found to produce a weak bulk heating of the electron radiation belt, and it also produces an energetic tail on the electron energy distribution. The amount of energization depends on the robustness of the solar wind compressions and on the amplitude of the chorus and/or EMIC waves. Chorus-catalyzed pumping is better at energizing medium-energy (50-200 keV) electrons than it is at energizing higher-energy electrons; at high energies (500 keV-2 MeV) EMIC-catalyzed pumping is a stronger energizer. The magnetic pumping simulation results are compared with energy diffusion calculations for chorus waves in the dayside magnetosphere; in general, compressional magnetic pumping is found to be weaker at accelerating electrons than is chorus-driven energy diffusion. In circumstances when solar wind compressions are robust and when EMIC waves are present in the dayside magnetosphere without the presence of chorus, EMIC-catalyzed magnetic pumping could be the dominant energization mechanism in the dayside magnetosphere, but at such times loss cone losses will be strong.

Transient proton inflows during illumination of anaerobic Halobacterium halobium cells

NASA Technical Reports Server (NTRS)

Helgerson, S. L.; Stoeckenius, W.

1985-01-01

The roles of bacteriorhodopsin (bR), halorhodopsin (hR), and the H(+)-ATPase in the proton uptake in intact cells are examined. The Halobacterium halobium strains and solutions utilized in the experiment, and the techniques for measuring extracellular pH changes and intracellular K(+) concentrations are described. It is observed that in Halobacterium halobium strain R1, containing bR and hR, the light-driven proton uptake is divided into three transient inflows superimposed on the larger proton outflow. Under anaerobic conditions early proton uptake consists of an inflow which can be blocked with Dio-9 and a second inflow that can be eliminated by low concentrations (less than 125 nm) of triphenyltin chloride (TPT). The effects of Dio-9 and TPT on the passive proton-hydroxyl permeability of the cell membrane are investigated. A third transient light-driven proton flow observed at later times of illumination is studied. The data reveal that the first proton inflow correlates with proton dependent ATP synthesis; the second inflow is a passive uptake through an unidentified channel in response to electrogenic chloride pumping by bR and/or hR; and the third inflow correlates with the Na(+)/H(+) antiporter function.

Sulfate-reducing bacteria: Microbiology and physiology

NASA Technical Reports Server (NTRS)

Peck, H. D.

1985-01-01

The sulfate reducing bacteria, the first nonphotosynthetic anaerobic bacteria demonstrated to contain c type cytochromes, perform electron transfer coupled to phosphorylation. A new bioenergetic scheme for the formation of a proton gradient for growth of Desulfovibrio on organic substrates and sulfate involving vectors electron transfer and consistent with the cellular localization of enzymes and electron transfer components was proposed. Hydrogen is produced in the cytoplasm from organic substrates and, as a permease molecule diffuses rapidly across the cytoplasmic membrane, it is oxidized to protons and electrons by the periplasmic hydrogenase. The electrons only are transferred across the cytoplasmic membrane to the cytoplasm where they are used to reduce sulfate to sulfide. The protons are used for transport or to drive a reversible ATPOSE. The net effect is the transfer of protons across the cytoplasmic membrane with the intervention of a proton pump. This type of H2 cycling is relevant to the bioenergetics of other types of anaerobic microorganisms.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gust, Devens; Moore, Thomas A.; Moore, Ana L.

OAK B188 The goal of this project is to mimic the energy transduction processes by which photosynthetic organisms harvest sunlight and convert it to forms of energy that are more easily used and stored. The results may lead to new technologies for solar energy harvesting based on the natural photosynthetic process. They may also enrich our understanding and control of photosynthesis in living organisms, and lead to methods for increasing natural biomass production, carbon dioxide removal, and oxygen generation. In our work to date, we have learned how to make synthetic antenna and reaction center molecules that absorb light andmore » undergo photoinduced electron transfer to generate long-lived, energetic charge-separated states. We have assembled a prototype system in which artificial reaction centers are inserted into liposomes (artificial cell-like constructs), where they carry out light-driven transmembrane translocation of hydrogen ions to generate proton motive force. By insertion of natural ATP synthase into the liposomal bilayer, this proton motive force has been used to power the synthesis of ATP. ATP is a natural biological energy currency. We are carrying out a systematic investigation of these artificial photosynthetic energy harvesting constructs in order to understand better how they operate. In addition, we are exploring strategies for reversing the direction of the light-powered proton pumping. Most recently, we have extended these studies to develop a light-powered transmembrane calcium ion pump that converts sunlight into energy stored as a calcium ion concentration gradient across a lipid bilayer.« less

Characterizing the proton loading site in cytochrome c oxidase.

PubMed

Lu, Jianxun; Gunner, M R

2014-08-26

Cytochrome c oxidase (CcO) uses the energy released by reduction of O2 to H2O to drive eight charges from the high pH to low pH side of the membrane, increasing the electrochemical gradient. Four electrons and protons are used for chemistry, while four more protons are pumped. Proton pumping requires that residues on a pathway change proton affinity through the reaction cycle to load and then release protons. The protonation states of all residues in CcO are determined in MultiConformational Continuum Electrostatics simulations with the protonation and redox states of heme a, a3, Cu(B), Y288, and E286 used to define the catalytic cycle. One proton is found to be loaded and released from residues identified as the proton loading site (PLS) on the P-side of the protein in each of the four CcO redox states. Thus, the same proton pumping mechanism can be used each time CcO is reduced. Calculations with structures of Rhodobacter sphaeroides, Paracoccus denitrificans, and bovine CcO derived by crystallography and molecular dynamics show the PLS functions similarly in different CcO species. The PLS is a cluster rather than a single residue, as different structures show 1-4 residues load and release protons. However, the proton affinity of the heme a3 propionic acids primarily determines the number of protons loaded into the PLS; if their proton affinity is too low, less than one proton is loaded.

Characterizing the proton loading site in cytochrome c oxidase

PubMed Central

Lu, Jianxun; Gunner, M. R.

2014-01-01

Cytochrome c oxidase (CcO) uses the energy released by reduction of O2 to H2O to drive eight charges from the high pH to low pH side of the membrane, increasing the electrochemical gradient. Four electrons and protons are used for chemistry, while four more protons are pumped. Proton pumping requires that residues on a pathway change proton affinity through the reaction cycle to load and then release protons. The protonation states of all residues in CcO are determined in MultiConformational Continuum Electrostatics simulations with the protonation and redox states of heme a, a3, CuB, Y288, and E286 used to define the catalytic cycle. One proton is found to be loaded and released from residues identified as the proton loading site (PLS) on the P-side of the protein in each of the four CcO redox states. Thus, the same proton pumping mechanism can be used each time CcO is reduced. Calculations with structures of Rhodobacter sphaeroides, Paracoccus denitrificans, and bovine CcO derived by crystallography and molecular dynamics show the PLS functions similarly in different CcO species. The PLS is a cluster rather than a single residue, as different structures show 1–4 residues load and release protons. However, the proton affinity of the heme a3 propionic acids primarily determines the number of protons loaded into the PLS; if their proton affinity is too low, less than one proton is loaded. PMID:25114210

Analogies between respiration and a light-driven proton pump as sources of energy for active glutamate transport in Halobacterium halobium

NASA Technical Reports Server (NTRS)

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.

Recent progress on beam stability study in the PSR

NASA Astrophysics Data System (ADS)

Wang, Tai-Sen F.; Channell, Paul J.; Cooper, Richard K.; Fitzgerald, Daniel H.; Hardek, Tom; Hutson, Richard; Jason, Andrew J.; Macek, Robert J.; Plum, Michael A.; Wilkinson, Carol

A fast transverse instability has been observed in the Los Alamos Proton Storage Ring (PSR) when the injected beam intensity reaches more than 2 (times) 10(exp 13) protons per pulse. Understanding the cause and control of this instability has taken on new importance as the neutron-scattering community considers the next generation of accelerator-driven spallation-neutron sources, which call for peak-proton intensities of 10(exp 14) per pulse or higher. Previous observations and theoretical studies indicate that the instability in the PSR is most likely driven by electrons trapped within the proton beam. Recent studies using an experimental electron-clearing system and voltage-biased pinger-electrodes for electron clearing and collection support this hypothesis. Experiments have also been performed to study the instability threshold when varying the electron production rate. Theoretical studies include a computer simulation of a simplified model for the e -- p instability and the investigation of possible electron confinement in the ring-element magnetic fields. This paper reports some recent results from these studies.

Proton-pumping rhodopsins are abundantly expressed by microbial eukaryotes in a high-Arctic fjord.

PubMed

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.

Light-driven production of ATP catalysed by F0F1-ATP synthase in an artificial photosynthetic membrane

NASA Astrophysics Data System (ADS)

Steinberg-Yfrach, Gali; Rigaud, Jean-Louis; Durantini, Edgardo N.; Moore, Ana L.; Gust, Devens; Moore, Thomas A.

1998-04-01

Energy-transducing membranes of living organisms couple spontaneous to non-spontaneous processes through the intermediacy of protonmotive force (p.m.f.) - an imbalance in electrochemical potential of protons across the membrane. In most organisms, p.m.f. is generated by redox reactions that are either photochemically driven, such as those in photosynthetic reaction centres, or intrinsically spontaneous, such as those of oxidative phosphorylation in mitochondria. Transmembrane proteins (such as the cytochromes and complexes I, III and IV in the electron-transport chain in the inner mitochondrial membrane) couple the redox reactions to proton translocation, thereby conserving a fraction of the redox chemical potential as p.m.f. Many transducer proteins couple p.m.f. to the performance of biochemical work, such as biochemical synthesis and mechanical and transport processes. Recently, an artificial photosynthetic membrane was reported in which a photocyclic process was used to transport protons across a liposomal membrane, resulting in acidification of the liposome's internal volume. If significant p.m.f. is generated in this system, then incorporating an appropriate transducer into the liposomal bilayer should make it possible to drive a non-spontaneous chemical process. Here we report the incorporation of FOF1-ATP synthase into liposomes containing the components of the proton-pumping photocycle. Irradiation of this artificial membrane with visible light results in the uncoupler- and inhibitor-sensitive synthesis of adenosine triphosphate (ATP) against an ATP chemical potential of ~12kcalmol-1, with a quantum yield of more than 7%. This system mimics the process by which photosynthetic bacteria convert light energy into ATP chemical potential.

Trypanosoma cruzi H+-ATPase 1 (TcHA1) and 2 (TcHA2) genes complement yeast mutants defective in H+ pumps and encode plasma membrane P-type H+-ATPases with different enzymatic properties.

PubMed

Luo, Shuhong; Scott, David A; Docampo, Roberto

2002-11-15

Previous studies in Trypanosoma cruzi have shown that intracellular pH homeostasis requires ATP and is affected by H(+)-ATPase inhibitors, indicating a major role for ATP-driven proton pumps in intracellular pH control. In the present study, we report the cloning and sequencing of a pair of genes linked in tandem (TcHA1 and TcHA2) in T. cruzi which encode proteins with homology to fungal and plant P-type proton-pumping ATPases. The genes are expressed at the mRNA level in different developmental stages of T. cruzi: TcHA1 is expressed maximally in epimastigotes, whereas TcHA2 is expressed predominantly in trypomastigotes. The proteins predicted from the nucleotide sequence of the genes have 875 and 917 amino acids and molecular masses of 96.3 and 101.2 kDa, respectively. Full-length TcHA1 and an N-terminal truncated version of TcHA2 complemented a Saccharomyces cerevisiae strain deficient in P-type H(+)-ATPase activity, the proteins localized to the yeast plasma membrane, and ATP-driven proton pumping could be detected in proteoliposomes reconstituted from plasma membrane purified from transfected yeast. The reconstituted proton transport activity was reduced by inhibitors of P-type H(+)-ATPases. C-terminal truncation did not affect complementation of mutant yeast, suggesting the lack of C-terminal autoinhibitory domains in these proteins. ATPase activity in plasma membrane from TcHA1- and (N-terminal truncated) TcHA2-transfected yeast was inhibited to different extents by vanadate, whereas the latter yeast strain was more resistant to extremes of pH, suggesting that the native proteins may serve different functions at different stages in the T. cruzi life cycle.

Correlated proton-electron hole dynamics in protonated water clusters upon extreme ultraviolet photoionization

PubMed Central

Li, Zheng; Vendrell, Oriol

2016-01-01

The ultrafast nuclear and electronic dynamics of protonated water clusters H+(H2O)n after extreme ultraviolet photoionization is investigated. In particular, we focus on cluster cations with n = 3, 6, and 21. Upon ionization, two positive charges are present in the cluster related to the excess proton and the missing electron, respectively. A correlation is found between the cluster's geometrical conformation and initial electronic energy with the size of the final fragments produced. For situations in which the electron hole and proton are initially spatially close, the two entities become correlated and separate in a time-scale of 20 to 40 fs driven by strong non-adiabatic effects. PMID:26798842

Stable transport in proton driven fast ignition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bret, A.

2009-09-15

Proton beam transport in the context of proton driven fast ignition is usually assumed to be stable due to proton high inertia, but an analytical analysis of the process is still lacking. The stability of a charge and current neutralized proton beam passing through a plasma is therefore conducted here, for typical proton driven fast ignition parameters. In the cold regime, two fast growing modes are found, with an inverse growth rate much smaller than the beam time of flight to the target core. The stability issue is thus not so obvious, and kinetic effects are investigated. One unstable modemore » is found stabilized by the background plasma proton and electron temperatures. The second mode is also damped, providing the proton beam thermal spread is larger than {approx}10 keV. In fusion conditions, the beam propagation should therefore be stable.« less

Proton-driven electromagnetic instabilities in high-speed solar wind streams

NASA Technical Reports Server (NTRS)

Abraham-Shrauner, B.; Asbridge, J. R.; Bame, S. J.; Feldman, W. C.

1979-01-01

Electromagnetic instabilities of the field-aligned, right-hand circularly polarized magnetosonic wave and the left-hand circularly polarized Alfven wave driven by two drifted proton components are analyzed for model parameters determined from Imp 7 solar wind proton data measured during high-speed flow conditions. Growth rates calculated using bi-Lorentzian forms for the main and beam proton as well as core and halo electron velocity distributions do not differ significantly from those calculated using bi-Maxwellian forms. Using distribution parameters determined from 17 measured proton spectra, we show that considering the uncertainties the magnetosonic wave may be linearly stable and the Alfven wave is linearly unstable. Because proton velocity distribution function shapes are observed to persist for times long compared to the proton gyroperiod, the latter result suggests that linear stability theory fails for proton-driven ion cyclotron waves in the high-speed solar wind.

Infrared laser driven double proton transfer. An optimal control theory study

NASA Astrophysics Data System (ADS)

Abdel-Latif, Mahmoud K.; Kühn, Oliver

2010-02-01

Laser control of ultrafast double proton transfer is investigated for a two-dimensional model system describing stepwise and concerted transfer pathways. The pulse design has been done by employing optimal control theory in combination with the multiconfiguration time-dependent Hartree wave packet propagation. The obtained laser fields correspond to multiple pump-dump pulse sequences. Special emphasis is paid to the relative importance of stepwise and concerted transfer pathways for the driven wave packet and its dependence on the parameters of the model Hamiltonian as well as on the propagation time. While stepwise transfer is dominating in all cases considered, for high barrier systems concerted transfer proceeding via tunneling can make a contribution.

Real-time observation of intramolecular proton transfer in the electronic ground state of chloromalonaldehyde: an ab initio study of time-resolved photoelectron spectra.

PubMed

do N Varella, Márcio T; Arasaki, Yasuki; Ushiyama, Hiroshi; Takatsuka, Kazuo; Wang, Kwanghsi; McKoy, Vincent

2007-02-07

The authors report on studies of time-resolved photoelectron spectra of intramolecular proton transfer in the ground state of chloromalonaldehyde, employing ab initio photoionization matrix elements and effective potential surfaces of reduced dimensionality, wherein the couplings of proton motion to the other molecular vibrational modes are embedded by averaging over classical trajectories. In the simulations, population is transferred from the vibrational ground state to vibrationally hot wave packets by pumping to an excited electronic state and dumping with a time-delayed pulse. These pump-dump-probe simulations demonstrate that the time-resolved photoelectron spectra track proton transfer in the electronic ground state well and, furthermore, that the geometry dependence of the matrix elements enhances the tracking compared with signals obtained with the Condon approximation. Photoelectron kinetic energy distributions arising from wave packets localized in different basins are also distinguishable and could be understood, as expected, on the basis of the strength of the optical couplings in different regions of the ground state potential surface and the Franck-Condon overlaps of the ground state wave packets with the vibrational eigenstates of the ion potential surface.

Correlated proton-electron hole dynamics in protonated water clusters upon extreme ultraviolet photoionization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zheng; Vendrell, Oriol

2016-01-13

The ultrafast nuclear and electronic dynamics of protonated water clusters H+(H2O)n after extreme ultraviolet photoionization is investigated. In particular, we focus on cluster cations with n = 3, 6, and 21. Upon ionization, two positive charges are present in the cluster related to the excess proton and the missing electron, respectively. A correlation is found between the cluster's geometrical conformation and initial electronic energy with the size of the final fragments produced. As a result, for situations in which the electron hole and proton are initially spatially close, the two entities become correlated and separate in a time-scale of 20more » to 40 fs driven by strong non-adiabatic effects.« less

Development of a Compact Efficient Cooling Pump for Space Suit Life Support Systems

NASA Technical Reports Server (NTRS)

vanBoeyen, Roger W.; Reeh, Jonathan A.; Trevino, Luis

2008-01-01

With the increasing demands placed on extravehicular activity (EVA) for the International Space Station (ISS) assembly and maintenance, along with planned lunar and Martian missions, the need for increased human productivity and capability becomes ever more critical. This is most readily achieved by reduction in space suit weight and volume, and increased hardware reliability, durability, and operating lifetime. Considerable progress has been made with each successive generation of space suit design; from the Apollo A7L suit, to the current Shuttle Extravehicular Mobile Unit (EMU) suit, and the next generation Constellation Space Suit Element (CSSE). However, one area of space suit design which has continued to lag is the fluid pump used to drive the water cooling loop of the Primary Life Support System (PLSS). The two main types of fluid pumps typically used in space applications are rotodynamic pumps (pumping is achieved through a rotary vaned impeller) and displacement pumps (which includes rotary and diaphragm pumps). The rotating and moving parts found in the pumps and electric motor add significantly to the susceptibility to wear and friction, thermal mismatch, and complexity of the pumps. Electric motor-driven pumps capable of achieving high operational reliability are necessarily large, heavy, and energy inefficient. This report describes a development effort conducted for NASA by Lynntech, Inc., who recently demonstrated the feasibility of an electrochemically-driven fluid cooling pump. With no electric motor and minimal lightweight components, an electrochemically-driven pump is expected to be significantly smaller, lighter and achieve a longer life time than conventional rotodynamic and displacement pumps. By employing sulfonated polystyrene-based proton exchange membranes, rather than conventional Nafion membranes, a significant reduction in the actuator power consumption was demonstrated. It was also demonstrated that these membranes possess the necessary mechanical strength, durability, and temperature range for long life space operation. The preliminary design for a Phase II prototype pump compares very favorably to the fluid cooling pumps currently used in space suit portable life support systems (PLSS). Characteristics of the electrochemically-driven pump are described and the benefits of the technology as a replacement for electric motor pumps in mechanically pumped single-phase fluid loops (MPFLs) is discussed.

A quantum chemical study of the mechanism for proton-coupled electron transfer leading to proton pumping in cytochrome c oxidase

NASA Astrophysics Data System (ADS)

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.

Watching the electronic motions driven by a conical intersection

NASA Astrophysics Data System (ADS)

Jonas, David

2007-03-01

In chemistry, the fastest electronic rearrangements proceed through ``conical intersections'' between electronic potential energy surfaces. With sufficiently short pulses, the electronic motion can be isolated by polarized excitation of aligned electronic wavepackets at a conical intersection. Polarized femtosecond probing reveals signatures of electronic wavepacket motion (due to the energy gaps) and of electron transfer between orbitals (due to the couplings) driven by the conical intersection. After exciting a D4h symmetry silicon naphthalocyanine molecule onto a Jahn-Teller conical intersection in the first excited state, electronic motions cause a ˜100 fs drop in the pump-probe polarization anisotropy. The polarized vibrational modulations of the signal can be used to deduce the symmetry and stabilization energies for each vibration. The initial decay of the polarization anisotropy can be quantitatively predicted from these vibrational parameters. Both coupling and energy gap variations are important on the ˜100 fs timescale. A 1 meV stabilization drives electrons from orbital to orbital in 100 fs, and the theory indicates that a chemically reactive conical intersection with 1000x greater stabilization energy could cause electronic equilibration within 2 fs. We have recently carried out experiments on a nominally D2h symmetry free-base naphthalocyanine for which the splitting between x and y polarized transitions is not resolved in the linear spectrum. For this molecule, the anisotropy also decays on a similar timescale and exhibits damped modulations whose origin (vibrational or electronic) has not yet been determined. The role of the central protons and nominal D2h symmetry in the electronic dynamics will be discussed.

Laser-driven injector of electrons for IOTA

NASA Astrophysics Data System (ADS)

Romanov, Aleksandr

2017-03-01

Fermilab is developing the Integrable Optics Test Accelerator (IOTA) ring for experiments on nonlinear integrable optics. The machine will operate with either electron beams of 150 MeV or proton beams of 2.5 MeV energies, respectively. The stability of integrable optics depends critically on the precision of the magnetic lattice, which demands the use of beam-based lattice measurements for optics correction. In the proton mode, the low-energy proton beam does not represent a good probe for this application; hence we consider the use of a low-intensity reverse-injected electron beam of matched momentum (70 MeV). Such an injector could be implemented with the use of laser-driven acceleration techniques. This report presents the consideration for a laser-plasma injector for IOTA and discusses the requirements determined by the ring design.

Atomic model for the membrane-embedded VO motor of a eukaryotic V-ATPase.

PubMed

Mazhab-Jafari, Mohammad T; Rohou, Alexis; Schmidt, Carla; Bueler, Stephanie A; Benlekbir, Samir; Robinson, Carol V; Rubinstein, John L

2016-11-03

Vacuolar-type ATPases (V-ATPases) are ATP-powered proton pumps involved in processes such as endocytosis, lysosomal degradation, secondary transport, TOR signalling, and osteoclast and kidney function. ATP hydrolysis in the soluble catalytic V 1 region drives proton translocation through the membrane-embedded V O region via rotation of a rotor subcomplex. Variability in the structure of the intact enzyme has prevented construction of an atomic model for the membrane-embedded motor of any rotary ATPase. We induced dissociation and auto-inhibition of the V 1 and V O regions of the V-ATPase by starving the yeast Saccharomyces cerevisiae, allowing us to obtain a ~3.9-Å resolution electron cryomicroscopy map of the V O complex and build atomic models for the majority of its subunits. The analysis reveals the structures of subunits ac 8 c'c″de and a protein that we identify and propose to be a new subunit (subunit f). A large cavity between subunit a and the c-ring creates a cytoplasmic half-channel for protons. The c-ring has an asymmetric distribution of proton-carrying Glu residues, with the Glu residue of subunit c″ interacting with Arg735 of subunit a. The structure suggests sequential protonation and deprotonation of the c-ring, with ATP-hydrolysis-driven rotation causing protonation of a Glu residue at the cytoplasmic half-channel and subsequent deprotonation of a Glu residue at a luminal half-channel.

Proton pumping in the bc1 complex: a new gating mechanism that prevents short circuits.

PubMed

Crofts, Antony R; Lhee, Sangmoon; Crofts, Stephanie B; Cheng, Jerry; Rose, Stuart

2006-08-01

The Q-cycle mechanism of the bc1 complex explains how the electron transfer from ubihydroquinone (quinol, QH2) to cytochrome (cyt) c (or c2 in bacteria) is coupled to the pumping of protons across the membrane. The efficiency of proton pumping depends on the effectiveness of the bifurcated reaction at the Q(o)-site of the complex. This directs the two electrons from QH2 down two different pathways, one to the high potential chain for delivery to an electron acceptor, and the other across the membrane through a chain containing heme bL and bH to the Qi-site, to provide the vectorial charge transfer contributing to the proton gradient. In this review, we discuss problems associated with the turnover of the bc1 complex that center around rates calculated for the normal forward and reverse reactions, and for bypass (or short-circuit) reactions. Based on rate constants given by distances between redox centers in known structures, these appeared to preclude conventional electron transfer mechanisms involving an intermediate semiquinone (SQ) in the Q(o)-site reaction. However, previous research has strongly suggested that SQ is the reductant for O2 in generation of superoxide at the Q(o)-site, introducing an apparent paradox. A simple gating mechanism, in which an intermediate SQ mobile in the volume of the Q(o)-site is a necessary component, can readily account for the observed data through a coulombic interaction that prevents SQ anion from close approach to heme bL when the latter is reduced. This allows rapid and reversible QH2 oxidation, but prevents rapid bypass reactions. The mechanism is quite natural, and is well supported by experiments in which the role of a key residue, Glu-295, which facilitates proton transfer from the site through a rotational displacement, has been tested by mutation.

A spectroscopic investigation of the Schiff base reprotonation mechanism of bacteriorhodopsin

NASA Astrophysics Data System (ADS)

Russell, Terence Stephen

This thesis reports time-resolved visible spectroscopy experiments performed on the light-driven proton pumping protein, bacteriorhodopsin (bR), and a number of artificially produced analogs. These analogs comprise a variety of single and double amino acid substitutions produced in several of the residues previously implicated in proton transport in bR. Also addressed are the results of resonance Raman and FTIR difference spectroscopy which provide information about the vibrational modes of the protein. The results from these experiments confirm aspects of both structural and functional models of bR based on previous electron diffraction and spectroscopic data. During a phase of the proton pumping photocycle in bR known as Schiff base reprotonation (also referred to as M intermediate decay), a proton is transferred over a 12 A distance from a proton donor residue (Asp-96) to the light-absorbing active site. The behavior of the M intermediate was monitored by time-resolved visible spectroscopy. In the single substitution known as D96N, the Asp-96 residue was replaced with a less efficient proton donor, asparagine. This mutant exhibited an M intermediate which decayed slowly in comparison to that of wild-type bR. However, this effect was reversed with the double substitution, T46D/D96N. This result indicates that the proton donor group can be moved to another nearby location and still yield a system functionally similar to the native protein. Replacement of the donor group with a histidine, His-96, resulted in a photocycle similar to D96N above pH 7. However, below this pH, the M intermediate is not detected. FTIR difference spectroscopy indicates that the protonation state of the substituted His-96 residue influences the structure of the active site of bR which suggests that a proton that is associated with His-96 may move towards the active site and thereby block M intermediate formation. Finally, the residue Thr-89 was replaced with an asparagine. This substitution altered not only the vibrational modes of the protein but also its visible absorption, which indicates that Thr-89 interacts directly with the active site of bR. These results are used to correct and extend an overall molecular model of the proton transport mechanism in bacteriorhodopsin.

Voltage Dependence of Proton Pumping by Bacteriorhodopsin Mutants with Altered Lifetime of the M Intermediate

PubMed Central

Geibel, Sven; Lörinczi, Èva; Bamberg, Ernst; Friedrich, Thomas

2013-01-01

The light-driven proton pump bacteriorhodopsin (BR) from Halobacterium salinarum is tightly regulated by the [H+] gradient and transmembrane potential. BR exhibits optoelectric properties, since spectral changes during the photocycle are kinetically controlled by voltage, which predestines BR for optical storage or processing devices. BR mutants with prolonged lifetime of the blue-shifted M intermediate would be advantageous, but the optoelectric properties of such mutants are still elusive. Using expression in Xenopus oocytes and two-electrode voltage-clamping, we analyzed photocurrents of BR mutants with kinetically destabilized (F171C, F219L) or stabilized (D96N, D96G) M intermediate in response to green light (to probe H+ pumping) and blue laser flashes (to probe accumulation/decay of M). These mutants have divergent M lifetimes. As for BR-WT, this strictly correlates with the voltage dependence of H+ pumping. BR-F171C and BR-F219L showed photocurrents similar to BR-WT. Yet, BR-F171C showed a weaker voltage dependence of proton pumping. For both mutants, blue laser flashes applied during and after green-light illumination showed reduced M accumulation and shorter M lifetime. In contrast, BR-D96G and BR-D96N exhibited small photocurrents, with nonlinear current-voltage curves, which increased strongly in the presence of azide. Blue laser flashes showed heavy M accumulation and prolonged M lifetime, which accounts for the strongly reduced H+ pumping rate. Hyperpolarizing potentials augmented these effects. The combination of M-stabilizing and -destabilizing mutations in BR-D96G/F171C/F219L (BR-tri) shows that disruption of the primary proton donor Asp-96 is fatal for BR as a proton pump. Mechanistically, M destabilizing mutations cannot compensate for the disruption of Asp-96. Accordingly, BR-tri and BR-D96G photocurrents were similar. However, BR-tri showed negative blue laser flash-induced currents even without actinic green light, indicating that Schiff base deprotonation in BR-tri exists in the dark, in line with previous spectroscopic investigations. Thus, M-stabilizing mutations, including the triple mutation, drastically interfere with electrochemical H+ gradient generation. PMID:24019918

Aspartate-Histidine Interaction in the Retinal Schiff Base Counterion of the Light-Driven Proton Pump of Exiguobacterium sibiricum†

PubMed Central

Balashov, S.P.; Petrovskaya, L.E.; Lukashev, E.P.; Imasheva, E.S.; Dioumaev, A.K.; Wang, J.M.; Sychev, S.V.; Dolgikh, D.A.; Rubin, A.B.; Kirpichnikov, M.P.; Lanyi, J.K.

2012-01-01

One of the distinctive features of eubacterial retinal based proton pumps, proteorhodopsins, xanthorhodopsin and others, is hydrogen bonding of the key aspartate residue, the counterion to the retinal Schiff base, to a histidine. We describe properties of the recently found eubacterium proton pump from Exiguobacterium sibiricum (named ESR) expressed in E. coli, especially features that depend on Asp-His interaction, the protonation state of the key aspartate, Asp85, and its ability to accept proton from the Schiff base during the photocycle. Proton pumping by liposomes and E. coli cells containing ESR occurs in a broad pH range above pH 4.5. Large light-induced pH changes indicate that ESR is a potent proton pump. Replacement of His57 with methionine or asparagine strongly affects the pH dependent properties of ESR. In the H57M mutant a dramatic decrease in the quantum yield of chromophore fluorescence emission and a 45 nm blue shift of the absorption maximum upon raising the pH from 5 to 8 indicates deprotonation of the counterion with a pKa of 6.3, which is also the pKa at which the M intermediate is observed in the photocycle of the protein solubilized in detergent (DDM). This is in contrast with the wild type protein, in which the same experiments show that the major fraction of Asp85 is deprotonated at pH > 3 and that it protonates only at low pH, with a pKa of 2.3. The M intermediate in the wild type photocycle accumulates only at high pH, with an apparent pKa of 9 from deprotonation of a residue interacting with Asp85, presumably His57. In liposomes reconstituted with ESR the pKas for M formation and spectral shifts are 2–3 pH units lower than in DDM. The distinctively different pH dependencies of the protonation of Asp85 and the accumulation of the M intermediate in the wild type protein vs. the H57M mutant indicate that there is strong Asp-His interaction, which substantially lowers the pKa of Asp85 by stabilizing its deprotonated state. PMID:22738070

Optogenetic Acidification of Synaptic Vesicles and Lysosomes

PubMed Central

Grauel, M. Katharina; Wozny, Christian; Bentz, Claudia; Blessing, Anja; Rosenmund, Tanja; Jentsch, Thomas J.; Schmitz, Dietmar; Hegemann, Peter; Rosenmund, Christian

2016-01-01

Acidification is required for the function of many intracellular organelles, but methods to acutely manipulate their intraluminal pH have not been available. Here we present a targeting strategy to selectively express the light-driven proton pump Arch3 on synaptic vesicles. Our new tool, pHoenix, can functionally replace endogenous proton pumps, enabling optogenetic control of vesicular acidification and neurotransmitter accumulation. Under physiological conditions, glutamatergic vesicles are nearly full, as additional vesicle acidification with pHoenix only slightly increased the quantal size. By contrast, we found that incompletely filled vesicles exhibited a lower release probability than full vesicles, suggesting preferential exocytosis of vesicles with high transmitter content. Our subcellular targeting approach can be transferred to other organelles, as demonstrated for a pHoenix variant that allows light-activated acidification of lysosomes. PMID:26551543

Optogenetic acidification of synaptic vesicles and lysosomes.

PubMed

Rost, Benjamin R; Schneider, Franziska; Grauel, M Katharina; Wozny, Christian; Bentz, Claudia; Blessing, Anja; Rosenmund, Tanja; Jentsch, Thomas J; Schmitz, Dietmar; Hegemann, Peter; Rosenmund, Christian

2015-12-01

Acidification is required for the function of many intracellular organelles, but methods to acutely manipulate their intraluminal pH have not been available. Here we present a targeting strategy to selectively express the light-driven proton pump Arch3 on synaptic vesicles. Our new tool, pHoenix, can functionally replace endogenous proton pumps, enabling optogenetic control of vesicular acidification and neurotransmitter accumulation. Under physiological conditions, glutamatergic vesicles are nearly full, as additional vesicle acidification with pHoenix only slightly increased the quantal size. By contrast, we found that incompletely filled vesicles exhibited a lower release probability than full vesicles, suggesting preferential exocytosis of vesicles with high transmitter content. Our subcellular targeting approach can be transferred to other organelles, as demonstrated for a pHoenix variant that allows light-activated acidification of lysosomes.

Ligand protons in a frozen solution of copper histidine relax via a T1e-driven three-spin mechanism

NASA Astrophysics Data System (ADS)

Stoll, S.; Epel, B.; Vega, S.; Goldfarb, D.

2007-10-01

Davies electron-nuclear double resonance spectra can exhibit strong asymmetries for long mixing times, short repetition times, and large thermal polarizations. These asymmetries can be used to determine nuclear relaxation rates in paramagnetic systems. Measurements of frozen solutions of copper(L-histidine)2 reveal a strong field dependence of the relaxation rates of the protons in the histidine ligand, increasing from low (g‖) to high (g⊥) field. It is shown that this can be attributed to a concentration-dependent T1e-driven relaxation process involving strongly mixed states of three spins: the histidine proton, the Cu(II) electron spin of the same complex, and another distant electron spin with a resonance frequency differing from the spectrometer frequency approximately by the proton Larmor frequency. The protons relax more efficiently in the g⊥ region, since the number of distant electrons able to participate in this relaxation mechanism is higher than in the g‖ region. Analytical expressions for the associated nuclear polarization decay rate Teen-1 are developed and Monte Carlo simulations are carried out, reproducing both the field and the concentration dependences of the nuclear relaxation.

FTIR Studies of Internal Water Molecules of Bacteriorhodopsin: Structural Analysis of Halide-bound D85S and D212N Mutants in the Schiff Base Region

NASA Astrophysics Data System (ADS)

Shibata, Mikihiro; Kandori, Hideki

2007-12-01

Bacteriorhodopsin (BR), a membrane protein found in Halobacterium salinarum, functions as a light-driven proton pump. The Schiff base region has a quadropolar structure with positive charges located at the protonated Schiff base and Arg82, and counterbalancing negative charges located at Asp85 and Asp212 (Figure 1A). It is known that BR lacks a proton-pumping activity if Asp85 or Asp212 is neutralized by mutation. On the other hand, binding of C1- brings different effects for pumping functions in mutants at D85 and D212 position. While C1--bound D85T and D85S pump C1-, photovoltage measurements suggested that C1--bound D212N pumps protons at low pH. In this study, we measured low-temperature FTIR spectra of D85S and D212N containing various halides to compare the halide binding site of both proteins. In the case of D85S, the N-D stretching vibrations of the Schiff base were halide-dependent. This result suggests that the halide is a hydrogen-bond acceptor of the Schiff base, being consistent with the X-ray crystal structure. On the other hand, no halide dependence was observed for vibrational bands of the retinal skeleton and the Schiff base in the D212N mutant. This result suggests that the halide does not form a hydrogen bond with the Schiff base directly, unlike the mutation at D85 position. Halide-dependent water bands in the Schiff base region also differ between D85S and D212N. From these results, halide binding site of both proteins and role of two negative charges in BR will be discussed.

Exciton Absorption in Semiconductor Quantum Wells Driven by a Strong Intersubband Pump Field

NASA Technical Reports Server (NTRS)

Liu, Ansheng; Ning, Cun-Zheng

1999-01-01

Optical interband excitonic absorption of semiconductor quantum wells (QW's) driven by a coherent pump field is investigated based on semiconductor Bloch equations. The pump field has a photon energy close to the intersubband spacing between the first two conduction subbands in the QW's. An external weak optical field probes the interband transition. The excitonic effects and pump-induced population redistribution within the conduction subbands in the QW system are included. When the density of the electron-hole pairs in the QW structure is low, the pump field induces an Autler-Townes splitting of the exciton absorption spectrum. The split size and the peak positions of the absorption doublet depend not only on the pump frequency and intensity but also on the carrier density. As the density of the electron-hole pairs is increased, the split contrast (the ratio between the maximum and minimum values) is decreased because the exciton effect is suppressed at higher densities due to the many-body screening.

A miniature, nongassing electroosmotic pump operating at 0.5 V.

PubMed

Shin, Woonsup; Lee, Jong Myung; Nagarale, Rajaram Krishna; Shin, Samuel Jaeho; Heller, Adam

2011-03-02

Electroosmotic pumps are arguably the simplest of all pumps, consisting merely of two flow-through electrodes separated by a porous membrane. Most use platinum electrodes and operate at high voltages, electrolyzing water. Because evolved gas bubbles adhere and block parts of the electrodes and the membrane, steady pumping rates are difficult to sustain. Here we show that when the platinum electrodes are replaced by consumed Ag/Ag(2)O electrodes, the pumps operate well below 1.23 V, the thermodynamic threshold for electrolysis of water at 25 °C, where neither H(2) nor O(2) is produced. The pumping of water is efficient: 13 000 water molecules are pumped per reacted electron and 4.8 mL of water are pumped per joule at a flow rate of 0.13 mL min(-1) V(-1) cm(-2), and a flow rate per unit of power is 290 mL min(-1) W(-1). The water is driven by protons produced in the anode reaction 2Ag(s) + H(2)O → Ag(2)O(s) + 2H(+) + 2e(-), traveling through the porous membrane, consumed by hydroxide ions generated in the cathode reaction Ag(2)O(s) + 2 H(2)O + 2e(-) → 2Ag(s) + 2 OH(-). A pump of 2 mm thickness and 0.3 cm(2) cross-sectional area produces flow of 5-30 μL min(-1) when operating at 0.2-0.8 V and 0.04-0.2 mA. Its flow rate can be either voltage or current controlled. The flow rate suffices for the delivery of drugs, such as a meal-associated boli of insulin.

THE COUPLED EVOLUTION OF ELECTRONS AND IONS IN CORONAL MASS EJECTION-DRIVEN SHOCKS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manchester IV, W. B.; Van der Holst, B.; Toth, G.

2012-09-01

We present simulations of coronal mass ejections (CMEs) performed with a new two-temperature coronal model developed at the University of Michigan, which is able to address the coupled thermodynamics of the electron and proton populations in the context of a single fluid. This model employs heat conduction for electrons, constant adiabatic index ({gamma} = 5/3), and includes Alfven wave pressure to accelerate the solar wind. The Wang-Sheeley-Arge empirical model is used to determine the Alfven wave pressure necessary to produce the observed bimodal solar wind speed. The Alfven waves are dissipated as they propagate from the Sun and heat protonsmore » on open magnetic field lines to temperatures above 2 MK. The model is driven by empirical boundary conditions that includes GONG magnetogram data to calculate the coronal field, and STEREO/EUVI observations to specify the density and temperature at the coronal boundary by the Differential Emission Measure Tomography method. With this model, we simulate the propagation of fast CMEs and study the thermodynamics of CME-driven shocks. Since the thermal speed of the electrons greatly exceeds the speed of the CME, only protons are directly heated by the shock. Coulomb collisions low in the corona couple the protons and electrons allowing heat exchange between the two species. However, the coupling is so brief that the electrons never achieve more than 10% of the maximum temperature of the protons. We find that heat is able to conduct on open magnetic field lines and rapidly propagates ahead of the CME to form a shock precursor of hot electrons.« less

Regulatory assembly of the vacuolar proton pump VoV1-ATPase in yeast cells by FLIM-FRET

NASA Astrophysics Data System (ADS)

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.

Investigating the Proton Donor in the NO Reductase from Paracoccus denitrificans

PubMed Central

ter Beek, Josy; Krause, Nils; Ädelroth, Pia

2016-01-01

Variant nomenclature: the variants were made in the NorB subunit if not indicated by the superscript c, which are variants in the NorC subunit (e.g. E122A = exchange of Glu-122 in NorB for an Ala, E71cD; exchange of Glu-71 in NorC for an Asp). Bacterial NO reductases (NORs) are integral membrane proteins from the heme-copper oxidase superfamily. Most heme-copper oxidases are proton-pumping enzymes that reduce O2 as the last step in the respiratory chain. With electrons from cytochrome c, NO reductase (cNOR) from Paracoccus (P.) denitrificans reduces NO to N2O via the following reaction: 2NO+2e-+2H+→N2O+H2O. Although this reaction is as exergonic as O2-reduction, cNOR does not contribute to the electrochemical gradient over the membrane. This means that cNOR does not pump protons and that the protons needed for the reaction are taken from the periplasmic side of the membrane (since the electrons are donated from this side). We previously showed that the P. denitrificans cNOR uses a single defined proton pathway with residues Glu-58 and Lys-54 from the NorC subunit at the entrance. Here we further strengthened the evidence in support of this pathway. Our further aim was to define the continuation of the pathway and the immediate proton donor for the active site. To this end, we investigated the region around the calcium-binding site and both propionates of heme b3 by site directed mutagenesis. Changing single amino acids in these areas often had severe effects on cNOR function, with many variants having a perturbed active site, making detailed analysis of proton transfer properties difficult. Our data does however indicate that the calcium ligation sphere and the region around the heme b3 propionates are important for proton transfer and presumably contain the proton donor. The possible evolutionary link between the area for the immediate donor in cNOR and the proton loading site (PLS) for pumped protons in oxygen-reducing heme-copper oxidases is discussed. PMID:27030968

Investigating the Proton Donor in the NO Reductase from Paracoccus denitrificans.

PubMed

ter Beek, Josy; Krause, Nils; Ädelroth, Pia

2016-01-01

Variant nomenclature: the variants were made in the NorB subunit if not indicated by the superscript c, which are variants in the NorC subunit (e.g. E122A = exchange of Glu-122 in NorB for an Ala, E71cD; exchange of Glu-71 in NorC for an Asp). Bacterial NO reductases (NORs) are integral membrane proteins from the heme-copper oxidase superfamily. Most heme-copper oxidases are proton-pumping enzymes that reduce O2 as the last step in the respiratory chain. With electrons from cytochrome c, NO reductase (cNOR) from Paracoccus (P.) denitrificans reduces NO to N2O via the following reaction: 2NO+2e-+2H+→N2O+H2O. Although this reaction is as exergonic as O2-reduction, cNOR does not contribute to the electrochemical gradient over the membrane. This means that cNOR does not pump protons and that the protons needed for the reaction are taken from the periplasmic side of the membrane (since the electrons are donated from this side). We previously showed that the P. denitrificans cNOR uses a single defined proton pathway with residues Glu-58 and Lys-54 from the NorC subunit at the entrance. Here we further strengthened the evidence in support of this pathway. Our further aim was to define the continuation of the pathway and the immediate proton donor for the active site. To this end, we investigated the region around the calcium-binding site and both propionates of heme b3 by site directed mutagenesis. Changing single amino acids in these areas often had severe effects on cNOR function, with many variants having a perturbed active site, making detailed analysis of proton transfer properties difficult. Our data does however indicate that the calcium ligation sphere and the region around the heme b3 propionates are important for proton transfer and presumably contain the proton donor. The possible evolutionary link between the area for the immediate donor in cNOR and the proton loading site (PLS) for pumped protons in oxygen-reducing heme-copper oxidases is discussed.

Progress toward an explicit mechanistic model for the light-driven pump, bacteriorhodopsin

NASA Technical Reports Server (NTRS)

Lanyi, J. K.

1999-01-01

Recent crystallographic information about the structure of bacteriorhodopsin and some of its photointermediates, together with a large amount of spectroscopic and mutational data, suggest a mechanistic model for how this protein couples light energy to the translocation of protons across the membrane. Now nearing completion, this detailed molecular model will describe the nature of the steric and electrostatic conflicts at the photoisomerized retinal, as well as the means by which it induces proton transfers in the two half-channels leading to the two membrane surfaces, thereby causing unidirectional, uphill transport.

The emerging structure of vacuolar ATPases.

PubMed

Drory, Omri; Nelson, Nathan

2006-10-01

Bioenergetics and physiology of primary pumps have been revitalized by new insights into the mechanism of energizing biomembranes. Structural information is becoming available, and the three-dimensional structure of F-ATPase is being resolved. The growing understanding of the fundamental mechanism of energy coupling may revolutionize our view of biological processes. The F- and V-ATPases (vacuolar-type ATPase) exhibit a common mechanical design in which nucleotide-binding on the catalytic sector, through a cycle of conformation changes, drives the transmembrane passage of protons by turning a membrane-embedded rotor. This motor can run in forward or reverse directions, hydrolyzing ATP as it pumps protons uphill or creating ATP as protons flow downhill. In contrast to F-ATPases, whose primary function in eukaryotic cells is to form ATP at the expense of the proton-motive force (pmf), V-ATPases function exclusively as an ATP-dependent proton pump. The pmf generated by V-ATPases in organelles and membranes of eukaryotic cells is utilized as a driving force for numerous secondary transport processes. V- and F-ATPases have similar structure and mechanism of action, and several of their subunits evolved from common ancestors. Electron microscopy studies of V-ATPase revealed its general structure at low resolution. Recently, several structures of V-ATPase subunits, solved by X-ray crystallography with atomic resolution, were published. This, together with electron microscopy low-resolution maps of the whole complex, and biochemistry cross-linking experiments, allows construction of a structural model for a part of the complex that may be used as a working hypothesis for future research.

Proton transfer in the K-channel analog of B-type Cytochrome c oxidase from Thermus thermophilus.

PubMed

Woelke, Anna Lena; Wagner, Anke; Galstyan, Gegham; Meyer, Tim; Knapp, Ernst-Walter

2014-11-04

A key enzyme in aerobic metabolism is cytochrome c oxidase (CcO), which catalyzes the reduction of molecular oxygen to water in the mitochondrial and bacterial membranes. Substrate electrons and protons are taken up from different sides of the membrane and protons are pumped across the membrane, thereby generating an electrochemical gradient. The well-studied A-type CcO uses two different entry channels for protons: the D-channel for all pumped and two consumed protons, and the K-channel for the other two consumed protons. In contrast, the B-type CcO uses only a single proton input channel for all consumed and pumped protons. It has the same location as the A-type K-channel (and thus is named the K-channel analog) without sharing any significant sequence homology. In this study, we performed molecular-dynamics simulations and electrostatic calculations to characterize the K-channel analog in terms of its energetic requirements and functionalities. The function of Glu-15B as a proton sink at the channel entrance is demonstrated by its rotational movement out of the channel when it is deprotonated and by its high pKA value when it points inside the channel. Tyr-244 in the middle of the channel is identified as the valve that ensures unidirectional proton transfer, as it moves inside the hydrogen-bond gap of the K-channel analog only while being deprotonated. The electrostatic energy landscape was calculated for all proton-transfer steps in the K-channel analog, which functions via proton-hole transfer. Overall, the K-channel analog has a very stable geometry without large energy barriers.

Proton Transfer in the K-Channel Analog of B-Type Cytochrome c Oxidase from Thermus thermophilus

PubMed Central

Woelke, Anna Lena; Wagner, Anke; Galstyan, Gegham; Meyer, Tim; Knapp, Ernst-Walter

2014-01-01

A key enzyme in aerobic metabolism is cytochrome c oxidase (CcO), which catalyzes the reduction of molecular oxygen to water in the mitochondrial and bacterial membranes. Substrate electrons and protons are taken up from different sides of the membrane and protons are pumped across the membrane, thereby generating an electrochemical gradient. The well-studied A-type CcO uses two different entry channels for protons: the D-channel for all pumped and two consumed protons, and the K-channel for the other two consumed protons. In contrast, the B-type CcO uses only a single proton input channel for all consumed and pumped protons. It has the same location as the A-type K-channel (and thus is named the K-channel analog) without sharing any significant sequence homology. In this study, we performed molecular-dynamics simulations and electrostatic calculations to characterize the K-channel analog in terms of its energetic requirements and functionalities. The function of Glu-15B as a proton sink at the channel entrance is demonstrated by its rotational movement out of the channel when it is deprotonated and by its high pKA value when it points inside the channel. Tyr-244 in the middle of the channel is identified as the valve that ensures unidirectional proton transfer, as it moves inside the hydrogen-bond gap of the K-channel analog only while being deprotonated. The electrostatic energy landscape was calculated for all proton-transfer steps in the K-channel analog, which functions via proton-hole transfer. Overall, the K-channel analog has a very stable geometry without large energy barriers. PMID:25418102

Low-dose or standard-dose proton pump inhibitors for maintenance therapy of gastro-oesophageal reflux disease: a cost-effectiveness analysis.

PubMed

You, J H S; Lee, A C M; Wong, S C Y; Chan, F K L

2003-03-15

Studies on the use of low-dose proton pump inhibitor for the maintenance therapy of gastro-oesophageal reflux disease have shown that it might be comparable with standard-dose proton pump inhibitor treatment and superior to standard-dose histamine-2 receptor antagonist therapy. To compare the impact of standard-dose histamine-2 receptor antagonist, low-dose proton pump inhibitor and standard-dose proton pump inhibitor treatment for the maintenance therapy of gastro-oesophageal reflux disease on symptom control and health care resource utilization from the perspective of a public health organization in Hong Kong. A Markov model was designed to simulate, over 12 months, the economic and clinical outcomes of gastro-oesophageal reflux disease patients treated with standard-dose histamine-2 receptor antagonist, low-dose proton pump inhibitor and standard-dose proton pump inhibitor. The transition probabilities were derived from the literature. Resource utilization was retrieved from a group of gastro-oesophageal reflux disease patients in Hong Kong. Sensitivity analysis was conducted to examine the robustness of the model. The standard-dose proton pump inhibitor strategy was associated with the highest numbers of symptom-free patient-years (0.954 years) and quality-adjusted life-years gained (0.999 years), followed by low-dose proton pump inhibitor and standard-dose histamine-2 receptor antagonist. The direct medical cost per patient in the standard-dose proton pump inhibitor group (904 US dollars) was lower than those of the low-dose proton pump inhibitor and standard-dose histamine-2 receptor antagonist groups. The standard-dose proton pump inhibitor strategy appears to be the most effective and least costly for the maintenance management of patients with gastro-oesophageal reflux disease in Hong Kong.

Localization of Ubiquinone-8 in the Na+-pumping NADH:Quinone Oxidoreductase from Vibrio cholerae*

PubMed Central

Casutt, Marco S.; Nedielkov, Ruslan; Wendelspiess, Severin; Vossler, Sara; Gerken, Uwe; Murai, Masatoshi; Miyoshi, Hideto; Möller, Heiko M.; Steuber, Julia

2011-01-01

Na+ is the second major coupling ion at membranes after protons, and many pathogenic bacteria use the sodium-motive force to their advantage. A prominent example is Vibrio cholerae, which relies on the Na+-pumping NADH:quinone oxidoreductase (Na+-NQR) as the first complex in its respiratory chain. The Na+-NQR is a multisubunit, membrane-embedded NADH dehydrogenase that oxidizes NADH and reduces quinone to quinol. Existing models describing redox-driven Na+ translocation by the Na+-NQR are based on the assumption that the pump contains four flavins and one FeS cluster. Here we show that the large, peripheral NqrA subunit of the Na+-NQR binds one molecule of ubiquinone-8. Investigations of the dynamic interaction of NqrA with quinones by surface plasmon resonance and saturation transfer difference NMR reveal a high affinity, which is determined by the methoxy groups at the C-2 and C-3 positions of the quinone headgroup. Using photoactivatable quinone derivatives, it is demonstrated that ubiquinone-8 bound to NqrA occupies a functional site. A novel scheme of electron transfer in Na+-NQR is proposed that is initiated by NADH oxidation on subunit NqrF and leads to quinol formation on subunit NqrA. PMID:21885438

Linking Chemical Electron–Proton Transfer to Proton Pumping in Cytochrome c Oxidase: Broken-Symmetry DFT Exploration of Intermediates along the Catalytic Reaction Pathway of the Iron–Copper Dinuclear Complex

PubMed Central

2015-01-01

After a summary of the problem of coupling electron and proton transfer to proton pumping in cytochrome c oxidase, we present the results of our earlier and recent density functional theory calculations for the dinuclear Fe-a3–CuB reaction center in this enzyme. A specific catalytic reaction wheel diagram is constructed from the calculations, based on the structures and relative energies of the intermediate states of the reaction cycle. A larger family of tautomers/protonation states is generated compared to our earlier work, and a new lowest-energy pathway is proposed. The entire reaction cycle is calculated for the new smaller model (about 185–190 atoms), and two selected arcs of the wheel are chosen for calculations using a larger model (about 205 atoms). We compare the structural and redox energetics and protonation calculations with available experimental data. The reaction cycle map that we have built is positioned for further improvement and testing against experiment. PMID:24960612

Physiological uncoupling of mitochondrial oxidative phosphorylation. Studies in different yeast species.

PubMed

Guerrero-Castillo, Sergio; Araiza-Olivera, Daniela; Cabrera-Orefice, Alfredo; Espinasa-Jaramillo, Juan; Gutiérrez-Aguilar, Manuel; Luévano-Martínez, Luís A; Zepeda-Bastida, Armando; Uribe-Carvajal, Salvador

2011-06-01

Under non-phosphorylating conditions a high proton transmembrane gradient inhibits the rate of oxygen consumption mediated by the mitochondrial respiratory chain (state IV). Slow electron transit leads to production of reactive oxygen species (ROS) capable of participating in deleterious side reactions. In order to avoid overproducing ROS, mitochondria maintain a high rate of O(2) consumption by activating different exquisitely controlled uncoupling pathways. Different yeast species possess one or more uncoupling systems that work through one of two possible mechanisms: i) Proton sinks and ii) Non-pumping redox enzymes. Proton sinks are exemplified by mitochondrial unspecific channels (MUC) and by uncoupling proteins (UCP). Saccharomyces. cerevisiae and Debaryomyces hansenii express highly regulated MUCs. Also, a UCP was described in Yarrowia lipolytica which promotes uncoupled O(2) consumption. Non-pumping alternative oxido-reductases may substitute for a pump, as in S. cerevisiae or may coexist with a complete set of pumps as in the branched respiratory chains from Y. lipolytica or D. hansenii. In addition, pumps may suffer intrinsic uncoupling (slipping). Promising models for study are unicellular parasites which can turn off their aerobic metabolism completely. The variety of energy dissipating systems in eukaryote species is probably designed to control ROS production in the different environments where each species lives.

Biosolar energy generation and harvesting from biomolecule-copolymer hybrid systems

NASA Astrophysics Data System (ADS)

Chu, Bong-Chieh Benjamin

Alternative energy sources have become an increasingly important topic as energy needs outpace supply. Furthermore, as the world moves into the digital age of portable electronics, highly efficient and lightweight energy sources will need to be developed. Current technology, such as lithium ion batteries, provide enough power to run portable electronics for hours or days, but can still allow for improvement in their power density (W/kg). Utilizing energy-transducing membrane proteins, which are by nature highly efficient, it is possible to engineer biological-based energy sources with energy densities far greater than any solid-state systems. Furthermore, solar powered membrane proteins have the added benefit of a virtually unlimited supply of energy. This work has developed protein-polymer hybrid films and nanoscale vesicles for a variety of applications from fuel-cell technology to biological-based photovoltaics. Bacteriorhodopsin (BR), a light-activated proton pump, and Cytochrome C Oxidase (COX), a protein involved in the electron transport chain in mitochondria, were reconstituted into biomimetic triblock copolymer membranes. Block copolymer membranes mimic the amphiphilic nature of a natural lipid bilayer but exhibit greater mechanical stability due to UV-polymerizable endgroups. In BR/COX functionalized nanovesicles, proton gradients generated by the light-activated proton pumping of BR are used to drive COX in reverse to generate electrons, providing a hybrid biologically-active polymer to convert solar energy to chemical energy, and finally to electrical energy. This work has found protein activity in planar membranes through the photoelectric current generation by BR and the proton pumping activity of BR-functionalized polymer membranes deposited onto proton exchange membranes, as well as the coupled functionality of BR and COX through current generation in cyclic voltammetry and direct current measurements. Current switching between light and dark environments of composite BR/COX polymer vesicles show a light-dependent current generation with current changes as high as 10muA. Furthermore, electrode modifications were made using polymer and polymer/carbon nanotube (CNT) coatings as anti-absorbent and conductive anti-absorbent layers for the purpose of a more robust electrode. These findings have shown that biological functionality can be engineered into synthetic polymers to make hybrid devices.

Correlation between proton pump inhibitors and risk of pyogenic liver abscess.

PubMed

Lin, Hsien-Feng; Liao, Kuan-Fu; Chang, Ching-Mei; Lin, Cheng-Li; Lai, Shih-Wei

2017-08-01

Little is known about the relationship between proton pump inhibitors use and pyogenic liver abscess. The objective of this study was to evaluate the correlation between proton pump inhibitors use and pyogenic liver abscess in Taiwan. This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. Subjects aged 20 to 84 who experienced their first episode of pyogenic liver abscess were enrolled as the case group (n = 1372). Randomly selected subjects aged 20 to 84 without pyogenic liver abscess were enrolled as the control group (n = 1372). Current use, early use, and late use of proton pump inhibitors was defined as subjects whose last one tablet for proton pump inhibitors was noted ≤30 days, between 31 to 90 days and ≥91 days before the date of admission for pyogenic liver abscess. Subjects who never received a prescription for proton pump inhibitors were defined as nonusers of proton pump inhibitors. A multivariable unconditional logistic regression model was used to measure the odds ratio and 95% confidence interval to evaluate the correlation between proton pump inhibitors use and pyogenic liver abscess. After adjusting for confounders, the adjusted odds ratio of pyogenic liver abscess was 7.59 for subjects with current use of proton pump inhibitors (95% confidence interval 5.05, 11.4), when compared with nonusers. Current use of proton pump inhibitors is associated with a greater risk of pyogenic liver abscess.

Harmonic generation by yeast cells in response to low-frequency electric fields

NASA Astrophysics Data System (ADS)

Nawarathna, D.; Claycomb, J. R.; Cardenas, G.; Gardner, J.; Warmflash, D.; Miller, J. H., Jr.; Widger, W. R.

2006-05-01

We report on harmonic generation by budding yeast cells (Saccharomyces cerevisiae, 108cells/ml ) in response to sinusoidal electric fields with amplitudes ranging from zero to 5V/cm in the frequency range 10-300Hz . The cell-generated harmonics are found to exhibit strong amplitude and frequency dependence. Sodium metavanadate, an inhibitor of the proton pump known as H+ -ATPase, and glucose, a substrate of H+ -ATPase, are found to increase harmonic production at low amplitudes while reducing it at large amplitudes. This P-type proton pump can be driven by an oscillatory transmembrane potential, and its nonlinear response is believed to be largely responsible for harmonic production at low frequencies in yeast cells. We find that the observed harmonics show dramatic changes with time and in their field and frequency dependence after perturbing the system by adding an inhibitor, substrate, or membrane depolarizer to the cell suspension.

Biomimetic Production of Hydrogen

NASA Astrophysics Data System (ADS)

Gust, Devens

2004-03-01

The basic reaction for hydrogen generation is formation of molecular hydrogen from two electrons and two protons. Although there are many possible sources for the protons and electrons, and a variety of mechanisms for providing the requisite energy for hydrogen synthesis, the most abundant and readily available source of protons and electrons is water, and the most attractive source of energy for powering the process is sunlight. Not surprisingly, living systems have evolved to take advantage of these sources for materials and energy. Thus, biology provides paradigms for carrying out the reactions necessary for hydrogen production. Photosynthesis in green plants uses sunlight as the source of energy for the oxidation of water to give molecular oxygen, protons, and reduction potential. Some photosynthetic organisms are capable of using this reduction potential, in the form of the reduced redox protein ferredoxin, to reduce protons and produce molecular hydrogen via the action of an hydrogenase enzyme. A variety of other organisms metabolize the reduced carbon compounds that are ultimately the major products of photosynthesis to produce molecular hydrogen. These facts suggest that it might be possible to use light energy to make molecular hydrogen via biomimetic constructs that employ principles similar to those used by natural organisms, or perhaps with hybrid "bionic" systems that combine biomimetic materials with natural enzymes. It is now possible to construct artificial photosynthetic systems that mimic some of the major steps in the natural process.(1) Artificial antennas based on porphyrins, carotenoids and other chromophores absorb light at various wavelengths in the solar spectrum and transfer the harvested excitation energy to artificial photosynthetic reaction centers.(2) In these centers, photoinduced electron transfer uses the energy from light to move an electron from a donor to an acceptor moiety, generating a high-energy charge-separated state. Subsequent electron transfer reactions further separate the electron and hole spatially, reducing the electronic coupling, slowing charge recombination, and lengthening the useful lifetime of the charge separation.(3) Still following the example of natural bacterial photosynthesis, these artificial reaction centers may be inserted into the lipid bilayer membranes of liposomes. There, they are used to power transmembrane proton pumps based on a redox loop that employs a lipid-soluble quinone molecule to shuttle hydrogen ions across the membrane, acidifying the interior of the liposome.(4) Finally, ATP synthase isolated from spinach can be inserted into the liposomal bilayer. Protons flow out of the liposome through the enzyme, driven by the gradient produced by the proton pump. The energy released is used to convert adenosine diphosphate into adenosine triphosphate, which is a major biological energy currency.(5) The chromophores used in these artificial photosynthetic reaction centers may also be attached to wide band gap nanoparticulate semiconductor electrodes, where their excited states inject electrons into the semiconductor, generating the radical cation of the chromophore. Such electrodes have been incorporated into a photoelectrochemical biofuel cell.(6) In the cell, NADH reduces the radical cation, regenerating the chromophore and ultimately producing NAD+. The NAD+ is recycled by converting it back to NADH via dehydrogenase enzymes that oxidize carbohydrates and similar reduced carbon compounds, including glucose, ethanol and methanol. Addition of a suitable cathode produces a cell that generates electric current through the combined action of light and enzymatic oxidation. The two examples of artificial photosynthesis discussed above are potential sources of the reducing power necessary for hydrogen production. A biomimetic approach to this goal is to couple an artificial photosynthetic system to an enzymatic system for hydrogen production isolated from a suitable organism. Some possible approaches to achieving this will be discussed. References (1) Gust, D.; Moore, T. A.; Moore, A. L. "Mimicking photosynthetic solar energy transduction," Acc. Chem. Res. 2001, 34, 40-48. (2) Kodis, G.; Liddell, P. A.; de la Garza, L.; Clausen, P. C.; Lindsey, J. S.; Moore, A. L.; Moore, T. A.; Gust, D. "Efficient energy transfer and electron transfer in an artificial photosynthetic antenna-reaction center complex," J. Phys. Chem. A 2002, 106, 2036-2048. (3) Liddell, P. A.; Kuciauskas, D.; Sumida, J. P.; Nash, B.; Nguyen, D.; Moore, A. L.; Moore, T. A.; Gust, D. "Photoinduced charge separation and charge recombination to a triplet state in a carotene-porphyrin-fullerene triad," J. Am. Chem. Soc. 1997, 119, 1400-1405. (4) Steinberg-Yfrach, G.; Liddell, P. A.; Hung, S.-C.; Moore, A. L.; Gust, D.; Moore, T. A. "Artificial photosynthetic reaction centers in liposomes: Photochemical generation of transmembrane proton potential," Nature 1997, 385, 239-241. (5) Steinberg-Yfrach, G.; Rigaud, J.-L.; Durantini, E. N.; Moore, A. L.; Gust, D.; Moore, T. A. "Light-driven production of ATP catalyzed by F0F1-ATP synthase in an artificial photosynthetic membrane," Nature 1998, 392, 479-482. (6) de la Garza, L.; Jeong, G.; Liddell, P. A.; Sotomura, T.; Moore, T. A.; Moore, A. L.; Gust, D. "Enzyme-based photoelectrochemical biofuel cell," J. Phys. Chem. B 2003, 107, 10252-10260.

Thermal-Error Regime in High-Accuracy Gigahertz Single-Electron Pumping

NASA Astrophysics Data System (ADS)

Zhao, R.; Rossi, A.; Giblin, S. P.; Fletcher, J. D.; Hudson, F. E.; Möttönen, M.; Kataoka, M.; Dzurak, A. S.

2017-10-01

Single-electron pumps based on semiconductor quantum dots are promising candidates for the emerging quantum standard of electrical current. They can transfer discrete charges with part-per-million (ppm) precision in nanosecond time scales. Here, we employ a metal-oxide-semiconductor silicon quantum dot to experimentally demonstrate high-accuracy gigahertz single-electron pumping in the regime where the number of electrons trapped in the dot is determined by the thermal distribution in the reservoir leads. In a measurement with traceability to primary voltage and resistance standards, the averaged pump current over the quantized plateau, driven by a 1-GHz sinusoidal wave in the absence of a magnetic field, is equal to the ideal value of e f within a measurement uncertainty as low as 0.27 ppm.

Protons and how they are transported by proton pumps.

PubMed

Buch-Pedersen, M J; Pedersen, B P; Veierskov, B; Nissen, P; Palmgren, M G

2009-01-01

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 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.

High Energy electron and proton acceleration by circularly polarized laser pulse from near critical density hydrogen gas target.

PubMed

Sharma, Ashutosh

2018-02-01

Relativistic electron rings hold the possibility of very high accelerating rates, and hopefully a relatively cheap and compact accelerator/collimator for ultrahigh energy proton source. In this work, we investigate the generation of helical shaped quasi-monoenergetic relativistic electron beam and high-energy proton beam from near critical density plasmas driven by petawatt-circularly polarized-short laser pulses. We numerically observe the efficient proton acceleration from magnetic vortex acceleration mechanism by using the three dimensional particle-in-cell simulations; proton beam with peak energy 350 MeV, charge ~10nC and conversion efficiency more than 6% (which implies 2.4 J proton beam out of the 40 J incident laser energy) is reported. We detailed the microphysics involved in the ion acceleration mechanism, which requires investigating the role of self-generated plasma electric and magnetic fields. The concept of efficient generation of quasi-monoenergetic electron and proton beam from near critical density gas targets may be verified experimentally at advanced high power - high repetition rate laser facilities e.g. ELI-ALPS. Such study should be an important step towards the development of high quality electron and proton beam.

Deletion of a unique loop in the mycobacterial F-ATP synthase γ subunit sheds light on its inhibitory role in ATP hydrolysis-driven H(+) pumping.

PubMed

Hotra, Adam; Suter, Manuel; Biuković, Goran; Ragunathan, Priya; Kundu, Subhashri; Dick, Thomas; Grüber, Gerhard

2016-05-01

The F1 FO -ATP synthase is one of the enzymes that is essential to meet the energy requirement of both the proliferating aerobic and hypoxic dormant stages of the life cycle of mycobacteria. Most F-ATP synthases consume ATP in the α3 :β3 headpiece to drive the γ subunit, which couples ATP cleavage with proton pumping in the c ring of FO via the bottom of the γ subunit. ATPase-driven H(+) pumping is latent in mycobacteria. The presence of a unique 14 amino acid residue loop of the mycobacterial γ subunit has been described and aligned in close vicinity to the c-ring loop Priya R et al. (2013) J Bioenerg Biomembr 45, 121-129 Here, we used inverted membrane vesicles (IMVs) of fast-growing Mycobacterium smegmatis and a variety of covalent and non-covalent inhibitors to characterize the ATP hydrolysis activity of the F-ATP synthase inside IMVs. These vesicles formed a platform to investigate the function of the unique mycobaterial γ loop by deleting the respective loop-encoding sequence (γ166-179 ) in the genome of M. smegmatis. ATP hydrolysis-driven H(+) pumping was observed in IMVs containing the Δγ166-179 mutant protein but not for IMVs containing the wild-type F-ATP synthase. In addition, when compared to the wild-type enzyme, IMVs containing the Δγ166-179 mutant protein showed increased ATP cleavage and lower levels of ATP synthesis, demonstrating that the loop affects ATPase activity, ATPase-driven H(+) pumping and ATP synthesis. These results further indicate that the loop may affect coupling of ATP hydrolysis and synthesis in a different mode. © 2016 Federation of European Biochemical Societies.

The mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type 2 (OCA2), and melanosomal pH.

PubMed

Brilliant, M H

2001-04-01

Recessive mutations of the mouse p (pink-eyed dilution) gene lead to hypopigmentation of the eyes, skin, and fur. Mice lacking a functional p protein have pink eyes and light gray fur (if non-agouti) or cream-colored fur (if agouti). The human orthologue is the P protein. Humans lacking a functional P protein have oculocutaneous albinism type 2 (OCA2). Melanocytes from p-deficient mice or OCA2 individuals contain small, minimally pigmented melanosomes. The mouse and human proteins are predicted to have 12 membrane spanning domains and possess significant sequence homology to a number of membrane transport proteins, some of which are involved in the transport of anions. The p protein has been localized to the melanosome membrane. Recently, it has been shown that melanosomes from p protein-deficient melanocytes have an abnormal pH. Melanosomes in cultured melanocytes derived from wild-type mice are typically acidic, whereas melanosomes from p protein-deficient mice are non-acidic. Melanosomes and related endosome-derived organelles (i.e., lysosomes) are thought to have an adenosine triphosphate (ATP)-driven proton pump that helps to generate an acidic lumen. To compensate for the charge of these protons, anions must also be transported to the lumen of the melanosome. In light of these observations, a model of p protein function is presented in which the p protein, together with the ATP-driven proton pump, regulates the pH of the melanosome.

Self-generated surface magnetic fields inhibit laser-driven sheath acceleration of high-energy protons.

PubMed

Nakatsutsumi, M; Sentoku, Y; Korzhimanov, A; Chen, S N; Buffechoux, S; Kon, A; Atherton, B; Audebert, P; Geissel, M; Hurd, L; Kimmel, M; Rambo, P; Schollmeier, M; Schwarz, J; Starodubtsev, M; Gremillet, L; Kodama, R; Fuchs, J

2018-01-18

High-intensity lasers interacting with solid foils produce copious numbers of relativistic electrons, which in turn create strong sheath electric fields around the target. The proton beams accelerated in such fields have remarkable properties, enabling ultrafast radiography of plasma phenomena or isochoric heating of dense materials. In view of longer-term multidisciplinary purposes (e.g., spallation neutron sources or cancer therapy), the current challenge is to achieve proton energies well in excess of 100 MeV, which is commonly thought to be possible by raising the on-target laser intensity. Here we present experimental and numerical results demonstrating that magnetostatic fields self-generated on the target surface may pose a fundamental limit to sheath-driven ion acceleration for high enough laser intensities. Those fields can be strong enough (~10 5  T at laser intensities ~10 21  W cm -2 ) to magnetize the sheath electrons and deflect protons off the accelerating region, hence degrading the maximum energy the latter can acquire.

Self-generated surface magnetic fields inhibit laser-driven sheath acceleration of high-energy protons

DOE PAGES

Nakatsutsumi, M.; Sentoku, Y.; Korzhimanov, A.; ...

2018-01-18

High-intensity lasers interacting with solid foils produce copious numbers of relativistic electrons, which in turn create strong sheath electric fields around the target. The proton beams accelerated in such fields have remarkable properties, enabling ultrafast radiography of plasma phenomena or isochoric heating of dense materials. In view of longer-term multidisciplinary purposes (e.g., spallation neutron sources or cancer therapy), the current challenge is to achieve proton energies well in excess of 100 MeV, which is commonly thought to be possible by raising the on-target laser intensity. Here we present experimental and numerical results demonstrating that magnetostatic fields self-generated on the targetmore » surface may pose a fundamental limit to sheath-driven ion acceleration for high enough laser intensities. Those fields can be strong enough (~10 5 T at laser intensities ~10 21 W cm –2) to magnetize the sheath electrons and deflect protons off the accelerating region, hence degrading the maximum energy the latter can acquire.« less

Self-generated surface magnetic fields inhibit laser-driven sheath acceleration of high-energy protons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakatsutsumi, M.; Sentoku, Y.; Korzhimanov, A.

High-intensity lasers interacting with solid foils produce copious numbers of relativistic electrons, which in turn create strong sheath electric fields around the target. The proton beams accelerated in such fields have remarkable properties, enabling ultrafast radiography of plasma phenomena or isochoric heating of dense materials. In view of longer-term multidisciplinary purposes (e.g., spallation neutron sources or cancer therapy), the current challenge is to achieve proton energies well in excess of 100 MeV, which is commonly thought to be possible by raising the on-target laser intensity. Here we present experimental and numerical results demonstrating that magnetostatic fields self-generated on the targetmore » surface may pose a fundamental limit to sheath-driven ion acceleration for high enough laser intensities. Those fields can be strong enough (~10 5 T at laser intensities ~10 21 W cm –2) to magnetize the sheath electrons and deflect protons off the accelerating region, hence degrading the maximum energy the latter can acquire.« less

Inward H+ pump xenorhodopsin: Mechanism and alternative optogenetic approach.

PubMed

Shevchenko, Vitaly; Mager, Thomas; Kovalev, Kirill; Polovinkin, Vitaly; Alekseev, Alexey; Juettner, Josephine; Chizhov, Igor; Bamann, Christian; Vavourakis, Charlotte; Ghai, Rohit; Gushchin, Ivan; Borshchevskiy, Valentin; Rogachev, Andrey; Melnikov, Igor; Popov, Alexander; Balandin, Taras; Rodriguez-Valera, Francisco; Manstein, Dietmar J; Bueldt, Georg; Bamberg, Ernst; Gordeliy, Valentin

2017-09-01

Generation of an electrochemical proton gradient is the first step of cell bioenergetics. In prokaryotes, the gradient is created by outward membrane protein proton pumps. Inward plasma membrane native proton pumps are yet unknown. We describe comprehensive functional studies of the representatives of the yet noncharacterized xenorhodopsins from Nanohaloarchaea family of microbial rhodopsins. They are inward proton pumps as we demonstrate in model membrane systems, Escherichia coli cells, human embryonic kidney cells, neuroblastoma cells, and rat hippocampal neuronal cells. We also solved the structure of a xenorhodopsin from the nanohalosarchaeon Nanosalina ( Ns XeR) and suggest a mechanism of inward proton pumping. We demonstrate that the Ns XeR is a powerful pump, which is able to elicit action potentials in rat hippocampal neuronal cells up to their maximal intrinsic firing frequency. Hence, inwardly directed proton pumps are suitable for light-induced remote control of neurons, and they are an alternative to the well-known cation-selective channelrhodopsins.

Terahertz-driven linear electron acceleration

PubMed Central

Nanni, Emilio A.; Huang, Wenqian R.; Hong, Kyung-Han; Ravi, Koustuban; Fallahi, Arya; Moriena, Gustavo; Dwayne Miller, R. J.; Kärtner, Franz X.

2015-01-01

The cost, size and availability of electron accelerators are dominated by the achievable accelerating gradient. Conventional high-brightness radio-frequency accelerating structures operate with 30–50 MeV m−1 gradients. Electron accelerators driven with optical or infrared sources have demonstrated accelerating gradients orders of magnitude above that achievable with conventional radio-frequency structures. However, laser-driven wakefield accelerators require intense femtosecond sources and direct laser-driven accelerators suffer from low bunch charge, sub-micron tolerances and sub-femtosecond timing requirements due to the short wavelength of operation. Here we demonstrate linear acceleration of electrons with keV energy gain using optically generated terahertz pulses. Terahertz-driven accelerating structures enable high-gradient electron/proton accelerators with simple accelerating structures, high repetition rates and significant charge per bunch. These ultra-compact terahertz accelerators with extremely short electron bunches hold great potential to have a transformative impact for free electron lasers, linear colliders, ultrafast electron diffraction, X-ray science and medical therapy with X-rays and electron beams. PMID:26439410

Chemiosmotic Energy Conservation in Dinoroseobacter shibae: Proton Translocation Driven by Aerobic Respiration, Denitrification, and Photosynthetic Light Reaction.

PubMed

Kirchhoff, Christian; Ebert, Matthias; Jahn, Dieter; Cypionka, Heribert

2018-01-01

Dinoroseobacter shibae is an aerobic anoxygenic phototroph and able to utilize light energy to support its aerobic energy metabolism. Since the cells can also grow anaerobically with nitrate and nitrite as terminal electron acceptor, we were interested in how the cells profit from photosynthesis during denitrification and what the steps of chemiosmotic energy conservation are. Therefore, we conducted proton translocation experiments and compared O 2 - , NO 3 - , and NO 2 - respiration during different light regimes and in the dark. We used wild type cells and transposon mutants with knocked-out nitrate- and nitrite- reductase genes ( napA and nirS ), as well as a mutant ( ppsR ) impaired in bacteriochlorophyll a synthesis. Light had a positive impact on proton translocation, independent of the type of terminal electron acceptor present. In the absence of an electron acceptor, however, light did not stimulate proton translocation. The light-driven add-on to proton translocation was about 1.4 H + /e - for O 2 respiration and about 1.1 H + /e - for NO 3 - and NO 2 - . We could see that the chemiosmotic energy conservation during aerobic respiration involved proton translocation, mediated by the NADH dehydrogenase, the cytochrome bc 1 complex, and the cytochrome c oxidase. During denitrification the last proton translocation step of the electron transport was missing, resulting in a lower H + /e - ratio during anoxia. Furthermore, we studied the type of light-harvesting and found that the cells were able to channel light from the green-blue spectrum most efficiently, while red light has only minor impact. This fits well with the depth profiles for D. shibae abundance in the ocean and the penetration depth of light with different wavelengths into the water column.

Tabletop Imaging of Structural Evolutions in Chemical Reactions

NASA Astrophysics Data System (ADS)

Ibrahim, Heide; Wales, Benji; Beaulieu, Samuel; Schmidt, Bruno E.; Thiré, Nicolas; Fowe, Emmanuel P.; Bisson, Éric; Hebeisen, Christoph T.; Wanie, Vincent; Giguére, Mathieu; Kieffer, Jean-Claude; Spanner, Michael; Bandrauk, André D.; Sanderson, Joseph; Schuurman, Michael S.; Légaré, François

The first high-resolution molecular movie of proton migration in the acetylene cation is obtained using a tabletop multiphoton pump-probe approach—an alternative to demanding free-electron-lasers and other VUV light sources when ionizing from the HOMO-1.

Multimorbidities and Overprescription of Proton Pump Inhibitors in Older Patients.

PubMed

Delcher, Anne; Hily, Sylvie; Boureau, Anne Sophie; Chapelet, Guillaume; Berrut, Gilles; de Decker, Laure

2015-01-01

To determine whether there is an association between overprescription of proton pump inhibitors (PPIs) and multimorbidities in older patients. Multicenter prospective study. Acute geriatric medicine at the University Hospital of Nantes and the Hospital of Saint-Nazaire. Older patients aged 75 and over hospitalized in acute geriatric medicine. Older patients in acute geriatric medicine who received proton pump inhibitors. Variables studied were individual multimorbidities, the burden of multimorbidity evaluated by the Cumulative Illness Rating Scale, age, sex, type of residence (living in nursing home or not), functional abilities (Lawton and Katz scales), nutritional status (Body Mass Index), and the type of concomitant medications (antiaggregant, corticosteroids', or anticoagulants). Overprescription of proton pump inhibitors was found in 73.9% older patients. In the full model, cardiac diseases (odds ratio [OR] = 4.17, p = 0.010), metabolic diseases (OR = 2.14, p = 0.042) and corticosteroids (OR = 5.39, p = 0.028) were significantly associated with overprescription of proton pump inhibitors. Esogastric diseases (OR = 0.49, p = 0.033) were negatively associated with overprescription of proton pump inhibitors. Cardiac diseases and metabolic diseases were significantly associated with overprescription of proton pump inhibitors.

The photochemical cycle of bacteriorhodopsin

NASA Technical Reports Server (NTRS)

Lozier, R. H.; Niederberger, W.

1977-01-01

The reaction cycle of bacteriorhodopsin in the purple membrane isolated from Halobacterium halobium has been studied by optical absorption spectroscopy using low-temperature and flash kinetic techniques. After absorption of light, bacteriorhodopsin passes through at least five distinct intermediates. The temperature and pH dependence of the absorbance changes suggests that branch points and/or reversible steps exist in this cycle. Flash spectroscopy in the presence of a pH-indicating dye shows that the transient release of a proton accompanies the photoreaction cycle. The proton release occurs from the exterior and the uptake is on the cytoplasmic side of the membrane, as required by the function of bacteriorhodopsin as a light-driven proton pump. Proton translocating steps connecting release and uptake are indicated by deuterium isotope effects on the kinetics of the cycle. The rapid decay of a light-induced linear dichroism shows that a chromophore orientation change occurs during the reaction cycle.

Japanese power electronics inverter technology and its impact on the American air conditioning industry

NASA Astrophysics Data System (ADS)

Ushimaru, Kenji

1990-08-01

Since 1983, technological advances and market growth of inverter-driven variable-speed heat pumps in Japan have been dramatic. The high level of market penetration was promoted by a combination of political, economic, and trade policies in Japan. A unique environment was created in which the leading domestic industries, microprocessor manufacturing, compressors for air conditioning and refrigerators, and power electronic devices, were able to direct the development and market success of inverter-driven heat pumps. As a result, leading U.S. variable-speed heat pump manufacturers should expect a challenge from the Japanese producers of power devices and microprocessors. Because of the vertically-integrated production structure in Japan, in contrast to the out-sourcing culture of the United States, price competition at the component level (such as inverters, sensors, and controls) may impact the structure of the industry more severely than final product sales.

Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: A meta-analysis

PubMed Central

Wang, Wei-Hong; Huang, Jia-Qing; Zheng, Ge-Fan; Xia, Harry Hua-Xiang; Wong, Wai-Man; Lam, Shiu-Kum; Wong, Benjamin Chun-Yu

2005-01-01

AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE). METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model. RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs, 1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs standard dose H2RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis. CONCLUSION: H2RAs are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis. PMID:15996033

[Influence of proton pump inhibitors on intestinal fermentative profile: a case-control study].

PubMed

Senderovky, Melisa; Lasa, Juan; Dima, Guillermo; Peralta, Daniel; Argüello, Mariano; Soifer, Luis

2014-01-01

Proton pump inhibitors could have an impact on the results of breath tests performed in patients with irritable bowel syndrome. This impact could be due to the development of small intestine bacterial overgrowth. To compare the prevalence of fermentative profile alterations of irritable bowel syndrome patients exposed and not-exposed to proton pump inhibitor therapy. Subjects with irritable bowel syndrome were enrolled. A validated questionnaire assessing symptom severity as well as proton pump inhibitor treatment was delivered. A lactulose breath test was undertaken by each enrolled subject. Fermentative profile (area under the curve of hydrogen excretion/time) was compared between proton pump inhibitors consumers and non-consumers. Furthermore, small intestine bacterial overgrowth prevalence was compared. Two hundred and twenty five patients were enrolled. No significant differences were found on the fermentative profile between groups [AUC mediana 3,776 (rango 2,124-5,571) vs 4,347 (rango 2,038-5,481), P = 0.3]. Small intestine bacterial overgrowth prevalence was similar as well [33% vs 27.5%]. These differences remained non-significant after adjusting for proton pump inhibitor dose and treatment time. Surprisingly, symptom score was significantly higher in those patients under proton pump inhibitor therapy [28.5 (23-26) vs 23 (15-29), P = 0.01]. Proton pump inhibitors have no significant influence on lactulose breath tests, regardless of the dosage and time of administration.

Progress in Fast Ignition Studies with Electrons and Protons

NASA Astrophysics Data System (ADS)

MacKinnon, A. J.; Akli, K. U.; Bartal, T.; Beg, F. N.; Chawla, S.; Chen, C. D.; Chen, H.; Chen, S.; Chowdhury, E.; Fedosejevs, R.; Freeman, R. R.; Hey, D.; Higginson, D.; Key, M. H.; King, J. A.; Link, A.; Ma, T.; MacPhee, A. G.; Offermann, D.; Ovchinnikov, V.; Pasley, J.; Patel, P. K.; Ping, Y.; Schumacher, D. W.; Stephens, R. B.; Tsui, Y. Y.; Wei, M. S.; Van Woerkom, L. D.

2009-09-01

Isochoric heating of inertially confined fusion plasmas by laser driven MeV electrons or protons is an area of great topical interest in the inertial confinement fusion community, particularly with respect to the fast ignition (FI) concept for initiating burn in a fusion capsule. In order to investigate critical aspects needed for a FI point design, experiments were performed to study 1) laser-to-electrons or protons conversion issues and 2) laser-cone interactions including prepulse effects. A large suite of diagnostics was utilized to study these important parameters. Using cone—wire surrogate targets it is found that pre-pulse levels on medium scale lasers such as Titan at Lawrence Livermore National Laboratory produce long scale length plasmas that strongly effect coupling of the laser to FI relevant electrons inside cones. The cone wall thickness also affects coupling to the wire. Conversion efficiency to protons has also been measured and modeled as a function of target thickness, material. Conclusions from the proton and electron source experiments will be presented. Recent advances in modeling electron transport and innovative target designs for reducing igniter energy and increasing gain curves will also be discussed. In conclusion, a program of study will be presented based on understanding the fundamental physics of the electron or proton source relevant to FI.

Molecular mechanisms for generating transmembrane proton gradients

PubMed Central

Gunner, M.R.; Amin, Muhamed; Zhu, Xuyu; Lu, Jianxun

2013-01-01

Membrane proteins use the energy of light or high energy substrates to build a transmembrane proton gradient through a series of reactions leading to proton release into the lower pH compartment (P-side) and proton uptake from the higher pH compartment (N-side). This review considers how the proton affinity of the substrates, cofactors and amino acids are modified in four proteins to drive proton transfers. Bacterial reaction centers (RCs) and photosystem II (PSII) carry out redox chemistry with the species to be oxidized on the P-side while reduction occurs on the N-side of the membrane. Terminal redox cofactors are used which have pKas that are strongly dependent on their redox state, so that protons are lost on oxidation and gained on reduction. Bacteriorhodopsin is a true proton pump. Light activation triggers trans to cis isomerization of a bound retinal. Strong electrostatic interactions within clusters of amino acids are modified by the conformational changes initiated by retinal motion leading to changes in proton affinity, driving transmembrane proton transfer. Cytochrome c oxidase (CcO) catalyzes the reduction of O2 to water. The protons needed for chemistry are bound from the N-side. The reduction chemistry also drives proton pumping from N- to P-side. Overall, in CcO the uptake of 4 electrons to reduce O2 transports 8 charges across the membrane, with each reduction fully coupled to removal of two protons from the N-side, the delivery of one for chemistry and transport of the other to the P-side. PMID:23507617

Protonic/electronic hybrid oxide transistor gated by chitosan and its full-swing low voltage inverter applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chao, Jin Yu; Ningbo Institute of Material Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201; Zhu, Li Qiang, E-mail: lqzhu@nimte.ac.cn

Modulation of charge carrier density in condensed materials based on ionic/electronic interaction has attracted much attention. Here, protonic/electronic hybrid indium-zinc-oxide (IZO) transistors gated by chitosan based electrolyte were obtained. The chitosan-based electrolyte illustrates a high proton conductivity and an extremely strong proton gating behavior. The transistor illustrates good electrical performances at a low operating voltage of ∼1.0 V such as on/off ratio of ∼3 × 10{sup 7}, subthreshold swing of ∼65 mV/dec, threshold voltage of ∼0.3 V, and mobility of ∼7 cm{sup 2}/V s. Good positive gate bias stress stabilities are obtained. Furthermore, a low voltage driven resistor-loaded inverter was built by using an IZO transistor inmore » series with a load resistor, exhibiting a linear relationship between the voltage gain and the supplied voltage. The inverter is also used for decreasing noises of input signals. The protonic/electronic hybrid IZO transistors have potential applications in biochemical sensors and portable electronics.« less

Novel target design for enhanced laser driven proton acceleration

NASA Astrophysics Data System (ADS)

Dalui, Malay; Kundu, M.; Tata, Sheroy; Lad, Amit D.; Jha, J.; Ray, Krishanu; Krishnamurthy, M.

2017-09-01

We demonstrate a simple method of preparing structured target for enhanced laser-driven proton acceleration under target-normal-sheath-acceleration scheme. A few layers of genetically modified, clinically grown micron sized E. Coli bacteria cell coated on a thin metal foil has resulted in an increase in the maximum proton energy by about 1.5 times and the total proton yield is enhanced by approximately 25 times compared to an unstructured reference foil at a laser intensity of 1019 W/cm2. Particle-in-cell simulations on the system shows that the structures on the target-foil facilitates anharmonic resonance, contributing to enhanced hot electron production which leads to stronger accelerating field. The effect is observed to grow as the number of structures is increased in the focal area of the laser pulse.

Multimorbidities and Overprescription of Proton Pump Inhibitors in Older Patients

PubMed Central

Delcher, Anne; Hily, Sylvie; Boureau, Anne Sophie; Chapelet, Guillaume; Berrut, Gilles; de Decker, Laure

2015-01-01

Objectives To determine whether there is an association between overprescription of proton pump inhibitors (PPIs) and multimorbidities in older patients. Design Multicenter prospective study. Setting Acute geriatric medicine at the University Hospital of Nantes and the Hospital of Saint-Nazaire. Participants Older patients aged 75 and over hospitalized in acute geriatric medicine. Measurements Older patients in acute geriatric medicine who received proton pump inhibitors. Variables studied were individual multimorbidities, the burden of multimorbidity evaluated by the Cumulative Illness Rating Scale, age, sex, type of residence (living in nursing home or not), functional abilities (Lawton and Katz scales), nutritional status (Body Mass Index), and the type of concomitant medications (antiaggregant, corticosteroids’, or anticoagulants). Results Overprescription of proton pump inhibitors was found in 73.9% older patients. In the full model, cardiac diseases (odds ratio [OR] = 4.17, p = 0.010), metabolic diseases (OR = 2.14, p = 0.042) and corticosteroids (OR = 5.39, p = 0.028) were significantly associated with overprescription of proton pump inhibitors. Esogastric diseases (OR = 0.49, p = 0.033) were negatively associated with overprescription of proton pump inhibitors. Conclusion Cardiac diseases and metabolic diseases were significantly associated with overprescription of proton pump inhibitors. PMID:26535585

The energetics of the primary proton transfer in bacteriorhodopsin revisited: it is a sequential light-induced charge separation after all.

PubMed

Braun-Sand, Sonja; Sharma, Pankaz K; Chu, Zhen T; Pisliakov, Andrei V; Warshel, Arieh

2008-05-01

The light-induced proton transport in bacteriorhodopsin has been considered as a model for other light-induced proton pumps. However, the exact nature of this process is still unclear. For example, it is not entirely clear what the driving force of the initial proton transfer is and, in particular, whether it reflects electrostatic forces or other effects. The present work simulates the primary proton transfer (PT) by a specialized combination of the EVB and the QCFF/PI methods. This combination allows us to obtain sufficient sampling and a quantitative free energy profile for the PT at different protein configurations. The calculated profiles provide new insight about energetics of the primary PT and its coupling to the protein conformational changes. Our finding confirms the tentative analysis of an earlier work (A. Warshel, Conversion of light energy to electrostatic energy in the proton pump of Halobacterium halobium, Photochem. Photobiol. 30 (1979) 285-290) and determines that the overall PT process is driven by the energetics of the charge separation between the Schiff base and its counterion Asp85. Apparently, the light-induced relaxation of the steric energy of the chromophore leads to an increase in the ion-pair distance, and this drives the PT process. Our use of the linear response approximation allows us to estimate the change in the protein conformational energy and provides the first computational description of the coupling between the protein structural changes and the PT process. It is also found that the PT is not driven by twist-modulated changes of the Schiff base's pKa, changes in the hydrogen bond directionality, or other non-electrostatic effects. Overall, based on a consistent use of structural information as the starting point for converging free energy calculations, we conclude that the primary event should be described as a light-induced formation of an unstable ground state, whose relaxation leads to charge separation and to the destabilization of the ion-pair state. This provides the driving force for the subsequent PT steps.

H+-type and OH--type biological protonic semiconductors and complementary devices

NASA Astrophysics Data System (ADS)

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

2013-10-01

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.

H+-type and OH−-type biological protonic semiconductors and complementary devices

PubMed Central

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

Activation Thermodynamics and H/D Kinetic Isotope Effect of the Hox to HredH+ Transition in [FeFe] Hydrogenase.

PubMed

Ratzloff, Michael W; Wilker, Molly B; Mulder, David W; Lubner, Carolyn E; Hamby, Hayden; Brown, Katherine A; Dukovic, Gordana; King, Paul W

2017-09-20

Molecular complexes between CdSe nanocrystals and Clostridium acetobutylicum [FeFe] hydrogenase I (CaI) enabled light-driven control of electron transfer for spectroscopic detection of redox intermediates during catalytic proton reduction. Here we address the route of electron transfer from CdSe→CaI and activation thermodynamics of the initial step of proton reduction in CaI. The electron paramagnetic spectroscopy of illuminated CdSe:CaI showed how the CaI accessory FeS cluster chain (F-clusters) functions in electron transfer with CdSe. The H ox →H red H + reduction step measured by Fourier-transform infrared spectroscopy showed an enthalpy of activation of 19 kJ mol -1 and a ∼2.5-fold kinetic isotope effect. Overall, these results support electron injection from CdSe into CaI involving F-clusters, and that the H ox →H red H + step of catalytic proton reduction in CaI proceeds by a proton-dependent process.

Effect of proton irradiation on superconductivity in optimally doped BaFe 2 ( As 1 - x P x ) 2 single crystals

DOE PAGES

Smylie, M. P.; Leroux, M.; Mishra, V.; ...

2016-03-10

In this paper, irradiation with 4 MeV protons was used to systematically introduce defects in single crystals of the iron-arsenide superconductor BaFe 2(As 1-xP x) 2, x = 0.33. The effect of disorder on the low-temperature behavior of the London penetration depth λ(T) and transition temperature T c was investigated. In nearly optimally doped samples with T c ~ 29 K, signatures of a superconducting gap with nodes were observed. Contrary to previous reports on electron-irradiated crystals, we do not see a disorder-driven lifting of accidental nodes, and we observe that proton-induced defects are weaker pair breakers than electron-induced defects.more » Finally, we attribute our findings to anisotropic electron scattering caused by proton irradiation defects.« less

Endoscopic and histopathologic gastric changes in chronic users of proton-pump inhibitors.

PubMed

Camilo, Sílvia Maria Perrone; Almeida, Élia Cláudia de Souza; Miranzi, Benito André Silveira; Silva, Juliano Carvalho; Nomelini, Rosemary Simões; Etchebehere, Renata Margarida

2015-01-01

Proton-pump inhibitors have been used for at least two decades. They are among the most commonly sold drugs in the world. However, some controversy remains about the indications for their use and the consequences of their prolonged use. To evaluate and compare the endoscopic and histopathologic gastric changes in chronic users of proton-pump inhibitors to changes in non-users. A prospective study performed at a tertiary Public Hospital involving 105 patients undergoing upper-gastrointestinal endoscopy. Subjects included 81 proton-pump inhibitor users and 24 non-users (control group). Biopsies of the antral-type mucosa, the antral-fundic transition, and the fundus were evaluated by the Sydney System. The presence of erosion or ulceration, lymphatic follicles, reactive gastropathy, and polypoid or epithelial hyperplasia was also determined. Serum levels of gastrin were measured. We found two polyps, one in each group, both of which were negative for Helicobacter pylori. There were two cases of parietal cell hyperplasia in users of proton-pump inhibitors. Gastrin was elevated in 28 users of proton-pump inhibitors and in four members of the control group. We did not find statistically significant differences in the endoscopic or histopathologic findings between the two groups. Chronic use of proton-pump inhibitors for the duration examined was not associated with significant gastric changes. An interesting finding was that the 4 chronic users of proton-pump inhibitors who had serum gastrin levels above 500 pg/mL also had positive serology for Chagas disease.

Proton-pumping mechanism of cytochrome c oxidase: A kinetic master-equation approach

PubMed Central

Kim, Young C.; Hummer, Gerhard

2011-01-01

Cytochrome c oxidase (CcO) is an efficient energy transducer that reduces oxygen to water and converts the released chemical energy into an electrochemical membrane potential. As a true proton pump, CcO translocates protons across the membrane against this potential. Based on a wealth of experiments and calculations, an increasingly detailed picture of the reaction intermediates in the redox cycle has emerged. However, the fundamental mechanism of proton pumping coupled to redox chemistry remains largely unresolved. Here we examine and extend a kinetic master-equation approach to gain insight into redox-coupled proton pumping in CcO. Basic principles of the CcO proton pump emerge from an analysis of the simplest kinetic models that retain essential elements of the experimentally determined structure, energetics, and kinetics, and that satisfy fundamental physical principles. The master-equation models allow us to address the question of how pumping can be achieved in a system in which all reaction steps are reversible. Whereas proton pumping does not require the direct modulation of microscopic reaction barriers, such kinetic gating greatly increases the pumping efficiency. Further efficiency gains can be achieved by partially decoupling the proton uptake pathway from the ative-site region. Such a mechanism is consistent with the proposed Glu valve, in which the side chain of a key glutamic acid shuttles between the D channel and the active-site region. We also show that the models predict only small proton leaks even in the absence of turnover. The design principles identified here for CcO provide a blueprint for novel biology-inspired fuel cells, and the master-equation formulation should prove useful also for other molecular machines. PMID:21946020

Concerted electron-proton transfer in the optical excitation of hydrogen-bonded dyes.

PubMed

Westlake, Brittany C; Brennaman, M Kyle; Concepcion, Javier J; Paul, Jared J; Bettis, Stephanie E; Hampton, Shaun D; Miller, Stephen A; Lebedeva, Natalia V; Forbes, Malcolm D E; Moran, Andrew M; Meyer, Thomas J; Papanikolas, John M

2011-05-24

The simultaneous, concerted transfer of electrons and protons--electron-proton transfer (EPT)--is an important mechanism utilized in chemistry and biology to avoid high energy intermediates. There are many examples of thermally activated EPT in ground-state reactions and in excited states following photoexcitation and thermal relaxation. Here we report application of ultrafast excitation with absorption and Raman monitoring to detect a photochemically driven EPT process (photo-EPT). In this process, both electrons and protons are transferred during the absorption of a photon. Photo-EPT is induced by intramolecular charge-transfer (ICT) excitation of hydrogen-bonded-base adducts with either a coumarin dye or 4-nitro-4'-biphenylphenol. Femtosecond transient absorption spectral measurements following ICT excitation reveal the appearance of two spectroscopically distinct states having different dynamical signatures. One of these states corresponds to a conventional ICT excited state in which the transferring H(+) is initially associated with the proton donor. Proton transfer to the base (B) then occurs on the picosecond time scale. The other state is an ICT-EPT photoproduct. Upon excitation it forms initially in the nuclear configuration of the ground state by application of the Franck-Condon principle. However, due to the change in electronic configuration induced by the transition, excitation is accompanied by proton transfer with the protonated base formed with a highly elongated (+)H ─ B bond. Coherent Raman spectroscopy confirms the presence of a vibrational mode corresponding to the protonated base in the optically prepared state.

Gyrokinetic stability of electron-positron-ion plasmas

NASA Astrophysics Data System (ADS)

Mishchenko, A.; Zocco, A.; Helander, P.; Könies, A.

2018-02-01

The gyrokinetic stability of electron-positron plasmas contaminated by an ion (proton) admixture is studied in a slab geometry. The appropriate dispersion relation is derived and solved. Stable K-modes, the universal instability, the ion-temperature-gradient-driven instability, the electron-temperature-gradient-driven instability and the shear Alfvén wave are considered. It is found that the contaminated plasma remains stable if the contamination degree is below some threshold and that the shear Alfvén wave can be present in a contaminated plasma in cases where it is absent without ion contamination.

FLARE VERSUS SHOCK ACCELERATION OF HIGH-ENERGY PROTONS IN SOLAR ENERGETIC PARTICLE EVENTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cliver, E. W.

2016-12-01

Recent studies have presented evidence for a significant to dominant role for a flare-resident acceleration process for high-energy protons in large (“gradual”) solar energetic particle (SEP) events, contrary to the more generally held view that such protons are primarily accelerated at shock waves driven by coronal mass ejections (CMEs). The new support for this flare-centric view is provided by correlations between the sizes of X-ray and/or microwave bursts and associated SEP events. For one such study that considered >100 MeV proton events, we present evidence based on CME speeds and widths, shock associations, and electron-to-proton ratios that indicates that eventsmore » omitted from that investigation’s analysis should have been included. Inclusion of these outlying events reverses the study’s qualitative result and supports shock acceleration of >100 MeV protons. Examination of the ratios of 0.5 MeV electron intensities to >100 MeV proton intensities for the Grechnev et al. event sample provides additional support for shock acceleration of high-energy protons. Simply scaling up a classic “impulsive” SEP event to produce a large >100 MeV proton event implies the existence of prompt 0.5 MeV electron events that are approximately two orders of magnitude larger than are observed. While classic “impulsive” SEP events attributed to flares have high electron-to-proton ratios (≳5 × 10{sup 5}) due to a near absence of >100 MeV protons, large poorly connected (≥W120) gradual SEP events, attributed to widespread shock acceleration, have electron-to-proton ratios of ∼2 × 10{sup 3}, similar to those of comparably sized well-connected (W20–W90) SEP events.« less

Flare vs. Shock Acceleration of High-energy Protons in Solar Energetic Particle Events

NASA Astrophysics Data System (ADS)

Cliver, E. W.

2016-12-01

Recent studies have presented evidence for a significant to dominant role for a flare-resident acceleration process for high-energy protons in large (“gradual”) solar energetic particle (SEP) events, contrary to the more generally held view that such protons are primarily accelerated at shock waves driven by coronal mass ejections (CMEs). The new support for this flare-centric view is provided by correlations between the sizes of X-ray and/or microwave bursts and associated SEP events. For one such study that considered >100 MeV proton events, we present evidence based on CME speeds and widths, shock associations, and electron-to-proton ratios that indicates that events omitted from that investigation’s analysis should have been included. Inclusion of these outlying events reverses the study’s qualitative result and supports shock acceleration of >100 MeV protons. Examination of the ratios of 0.5 MeV electron intensities to >100 MeV proton intensities for the Grechnev et al. event sample provides additional support for shock acceleration of high-energy protons. Simply scaling up a classic “impulsive” SEP event to produce a large >100 MeV proton event implies the existence of prompt 0.5 MeV electron events that are approximately two orders of magnitude larger than are observed. While classic “impulsive” SEP events attributed to flares have high electron-to-proton ratios (≳5 × 105) due to a near absence of >100 MeV protons, large poorly connected (≥W120) gradual SEP events, attributed to widespread shock acceleration, have electron-to-proton ratios of ˜2 × 103, similar to those of comparably sized well-connected (W20-W90) SEP events.

Effect of proton pump inhibitors on markers of risk for high-grade dysplasia and oesophageal cancer in Barrett's oesophagus.

PubMed

Hillman, L C; Chiragakis, L; Shadbolt, B; Kaye, G L; Clarke, A C

2008-02-15

It has been shown that the presence on diagnosis of endoscopic macroscopic markers indicates a high-risk group for Barrett's oesophagus. To determine whether proton pump inhibitor therapy prior to diagnosis of Barrett's oesophagus influences markers for risk development of subsequent high-grade dysplasia/adenocarcinoma. A review of all patients with Barrett's oesophagus entering a surveillance programme was undertaken. Five hundred and two patients diagnosed with Barrett's oesophagus were assessed on diagnosis for endoscopic macroscopic markers or low-grade dysplasia. Subsequent development of high-grade dysplasia/adenocarcinoma was documented. The relationship between the initiation of proton pump inhibitor therapy prior to the diagnosis of BE and the presence of macroscopic markers or low-grade dysplasia at entry was determined. Fourteen patients developed high-grade dysplasia/adenocarcinoma during surveillance. Patients who entered without prior proton pump inhibitor therapy were 3.4 times (95% CI: 1.98-5.85) more likely to have a macroscopic marker or low-grade dysplasia than those patients already on a proton pump inhibitor. Use of proton pump inhibitor therapy prior to diagnosis of Barrett's oesophagus significantly reduced the presence of markers used to stratify patient risk. Widespread use of proton pump inhibitors will confound surveillance strategies for patients with Barrett's oesophagus based on entry characteristics but is justified because of the lower risk of neoplastic progression.

Solid hydrogen target for laser driven proton acceleration

NASA Astrophysics Data System (ADS)

Perin, J. P.; Garcia, S.; Chatain, D.; Margarone, D.

2015-05-01

The development of very high power lasers opens up new horizons in various fields, such as laser plasma acceleration in Physics and innovative approaches for proton therapy in Medicine. Laser driven proton acceleration is commonly based on the so-called Target Normal Sheath Acceleration (TNSA) mechanisms: a high power laser is focused onto a solid target (thin metallic or plastic foil) and interact with matter at very high intensity, thus generating a plasma; as a consequence "hot" electrons are produced and move into the forward direction through the target. Protons are generated at the target rear side, electrons try to escape from the target and an ultra-strong quasi-electrostatic field (~1TV/m) is generated. Such a field can accelerate protons with a wide energy spectrum (1-200 MeV) in a few tens of micrometers. The proton beam characteristics depend on the laser parameters and on the target geometry and nature. This technique has been validated experimentally in several high power laser facilities by accelerating protons coming from hydrogenated contaminant (mainly water) at the rear of metallic target, however, several research groups are investigating the possibility to perform experiments by using "pure" hydrogen targets. In this context, the low temperature laboratory at CEA-Grenoble has developed a cryostat able to continuously produce a thin hydrogen ribbon (from 40 to 100 microns thick). A new extrusion concept, without any moving part has been carried out, using only the thermodynamic properties of the fluid. First results and perspectives are presented in this paper.

Proteorhodopsin Photocycle Kinetics Between pH 5 and pH 9.

PubMed

Köhler, Thomas; Weber, Ingrid; Glaubitz, Clemens; Wachtveitl, Josef

2017-05-01

The retinal protein proteorhodopsin is a homolog of the well-characterized light-driven proton pump bacteriorhodopsin. Basic mechanisms of proton transport seem to be conserved, but there are noticeable differences in the pH ranges of proton transport. Proton transport and protonation state of a carboxylic acid side chain, the primary proton acceptor, are correlated. In case of proteorhodopsin, the pK a of the primary proton acceptor Asp-97 (pK a  ≈ 7.5) is unexpectedly close to environmental pH (pH ≈ 8). A significant fraction of proteorhodopsin is possibly inactive at natural pH, in contrast to bacteriorhodopsin. We investigated photoinduced kinetics of proteorhodopsin between pH 5 and pH 9 by time resolved UV/vis absorption spectroscopy. Kinetics is inhomogeneous within that pH region and can be considered as a superposition of two fractions. These fractions are correlated with the Asp-97 titration curve. Beside Asp-97, protonation equilibria of other groups influence kinetics, but the observations do not point toward major differences of primary proton acceptor function in proteorhodopsin and bacteriorhodopsin. The pK a of proteorhodopsin and some of its variants is suspected to be an example of molecular adaptation to the physiology of the original organisms. © 2017 The American Society of Photobiology.

Ultrafast Intramolecular Electron and Proton Transfer in Bis(imino)isoindole Derivatives.

PubMed

Driscoll, Eric; Sorenson, Shayne; Dawlaty, Jahan M

2015-06-04

Concerted motion of electrons and protons in the excited state is pertinent to a wide range of chemical phenomena, including those relevant for solar-to-fuel light harvesting. The excited state dynamics of small proton-bearing molecules are expected to serve as models for better understanding such phenomena. In particular, for designing the next generation of multielectron and multiproton redox catalysts, understanding the dynamics of more than one proton in the excited state is important. Toward this goal, we have measured the ultrafast dynamics of intramolecular excited state proton transfer in a recently synthesized dye with two equivalent transferable protons. We have used a visible ultrafast pump to initiate the proton transfer in the excited state, and have probed the transient absorption of the molecule over a wide bandwidth in the visible range. The measurement shows that the signal which is characteristic of proton transfer emerges within ∼710 fs. To identify whether both protons were transferred in the excited state, we have measured the ultrafast dynamics of a related derivative, where only a single proton was available for transfer. The measured proton transfer time in that molecule was ∼427 fs. The observed dynamics in both cases were reasonably fit with single exponentials. Supported by the ultrafast observations, steady-state fluorescence, and preliminary computations of the relaxed excited states, we argue that the doubly protonated derivative most likely transfers only one of its two protons in the excited state. We have performed calculations of the frontier molecular orbitals in the Franck-Condon region. The calculations show that in both derivatives, the excitation is primarily from the HOMO to LUMO causing a large rearrangement of the electronic charge density immediately after photoexcitation. In particular, charge density is shifted away from the phenolic protons and toward the proton acceptor nitrogens. The proton transfer is hypothesized to occur both due to enhanced acidity of the phenolic proton and enhanced basicity of the nitrogen in the excited state. We hope this study can provide insight for better understanding of the general class of excited state concerted electron-proton dynamics.

Single mutations that redirect internal proton transfer in the ba3 oxidase from Thermus thermophilus

PubMed Central

Smirnova, Irina; Chang, Hsin-Yang; von Ballmoos, Christoph; Ädelroth, Pia; Gennis, Robert B.; Brzezinski, Peter

2014-01-01

The ba3-type cytochrome c oxidase from Thermus thermophilus is a membrane-bound proton pump. Results from earlier studies have shown that with the aa3-type oxidases proton uptake to the catalytic site and “pump site” occur simultaneously. However, with the ba3 oxidase the pump site is loaded before proton transfer to the catalytic site because the proton transfer to the latter is slower than with the aa3 oxidases. In addition, the timing of formation and decay of catalytic intermediates is different in the two types of oxidases. In the present study, we have investigated two mutant ba3 CytcOs in which residues of the proton pathway leading to the catalytic site as well as the pump site were exchanged, Thr312Val and Tyr244Phe. Even though the ba3 CytcO uses only a single proton pathway for transfer of the substrate and “pumped” protons, the amino-acid residue substitutions had distinctly different effects on the kinetics of proton transfer to the catalytic site and the pump site, respectively. The results indicate that the rates of these reactions can be modified independently by replacement of single residues within the proton pathway. Furthermore, the data suggest that the Thr312Val and Tyr244Phe mutations interfere with a structural rearrangement in the proton pathway that is rate limiting for proton transfer to the catalytic site. PMID:24004023

Concerted electron-proton transfer in the optical excitation of hydrogen-bonded dyes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westlake, Brittany C.; Brennaman, Kyle M.; Concepcion, Javier J.

2011-05-24

The simultaneous, concerted transfer of electrons and protons—electron-proton transfer (EPT)—is an important mechanism utilized in chemistry and biology to avoid high energy intermediates. There are many examples of thermally activated EPT in ground-state reactions and in excited states following photoexcitation and thermal relaxation. Here we report application of ultrafast excitation with absorption and Raman monitoring to detect a photochemically driven EPT process (photo-EPT). In this process, both electrons and protons are transferred during the absorption of a photon. Photo-EPT is induced by intramolecular charge-transfer (ICT) excitation of hydrogen-bonded-base adducts with either a coumarin dye or 4-nitro-4'-biphenylphenol. Femtosecond transient absorption spectralmore » measurements following ICT excitation reveal the appearance of two spectroscopically distinct states having different dynamical signatures. One of these states corresponds to a conventional ICT excited state in which the transferring H⁺ is initially associated with the proton donor. Proton transfer to the base (B) then occurs on the picosecond time scale. The other state is an ICT-EPT photoproduct. Upon excitation it forms initially in the nuclear configuration of the ground state by application of the Franck–Condon principle. However, due to the change in electronic configuration induced by the transition, excitation is accompanied by proton transfer with the protonated base formed with a highly elongated ⁺H–B bond. Coherent Raman spectroscopy confirms the presence of a vibrational mode corresponding to the protonated base in the optically prepared state.« less

Review article: relationship between the metabolism and efficacy of proton pump inhibitors--focus on rabeprazole.

PubMed

Horn, J

2004-11-01

Proton pump inhibitors are now considered the mainstay of treatment for acid-related disease. Although all proton pump inhibitors are highly effective, the antisecretory effects of different drugs in this class are not completely consistent across patients. One reason for this is the acid-suppressing effect of Helicobacter pylori infection, which may augment the actions of proton pump inhibitors. A second important reason for interpatient variability of the effects of proton pump inhibitors on acid secretion involves genetically determined differences in the metabolism of these drugs. This article focuses on the impact of genetic polymorphism of cytochrome P450 (CYP)2C19 on the pharmacokinetics and pharmacodynamics of proton pump inhibitors, particularly rabeprazole. Results reviewed indicate that the metabolism and pharmacokinetics of rabeprazole differ significantly from those of other proton pump inhibitors. Most importantly, the clearance of rabeprazole is largely nonenzymatic and less dependent on CYP2C19 than other drugs in its class. This results in greater consistency of pharmacokinetics for rabeprazole across a wide range of patients with acid-related disease, particularly those with different CYP2C19 genotypes. The pharmacodynamic profile for rabeprazole is also characterized by more rapid suppression of gastric acid secretion than with other proton pump inhibitors, which is also independent of CYP2C19 genotype. The favourable pharmacokinetic/pharmacodynamic profile for rabeprazole has been shown to result in high eradication rates for H. pylori in both normal and poor metabolizers. Pharmacodynamic results have also suggested that rabeprazole may be better suited than omeprazole as on-demand therapy for symptomatic gastro-oesophageal reflux disease. Finally, the use of rabeprazole is not complicated by clinically significant drug-drug interactions of the type that have been reported for omeprazole.

Activation Thermodynamics and H/D Kinetic Isotope Effect of the H ox to H red H + Transition in [FeFe] Hydrogenase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ratzloff, Michael W.; Wilker, Molly B.; Mulder, David W.

Molecular complexes between CdSe nanocrystals and Clostridium acetobutylicum [FeFe] hydrogenase I (CaI) enabled light-driven control of electron transfer for spectroscopic detection of redox intermediates during catalytic proton reduction. Here in this paper we address the route of electron transfer from CdSe→CaI and activation thermodynamics of the initial step of proton reduction in CaI. The electron paramagnetic spectroscopy of illuminated CdSe:CaI showed how the CaI accessory FeS cluster chain (F-clusters) functions in electron transfer with CdSe. The H ox→H redH + reduction step measured by Fourier-transform infrared spectroscopy showed an enthalpy of activation of 19 kJ mol -1 and a ~2.5-foldmore » kinetic isotope effect. Overall these results support electron injection from CdSe into CaI involving F-clusters, and that the H ox→H redH + step of catalytic proton reduction in CaI proceeds by a proton-dependent process.« less

Activation Thermodynamics and H/D Kinetic Isotope Effect of the H ox to H red H + Transition in [FeFe] Hydrogenase

DOE PAGES

Ratzloff, Michael W.; Wilker, Molly B.; Mulder, David W.; ...

2017-08-29

Molecular complexes between CdSe nanocrystals and Clostridium acetobutylicum [FeFe] hydrogenase I (CaI) enabled light-driven control of electron transfer for spectroscopic detection of redox intermediates during catalytic proton reduction. Here in this paper we address the route of electron transfer from CdSe→CaI and activation thermodynamics of the initial step of proton reduction in CaI. The electron paramagnetic spectroscopy of illuminated CdSe:CaI showed how the CaI accessory FeS cluster chain (F-clusters) functions in electron transfer with CdSe. The H ox→H redH + reduction step measured by Fourier-transform infrared spectroscopy showed an enthalpy of activation of 19 kJ mol -1 and a ~2.5-foldmore » kinetic isotope effect. Overall these results support electron injection from CdSe into CaI involving F-clusters, and that the H ox→H redH + step of catalytic proton reduction in CaI proceeds by a proton-dependent process.« less

Electrogenic active proton pump in Rana esculenta skin and its role in sodium ion transport.

PubMed

Ehrenfeld, J; Garcia-Romeu, F; Harvey, B J

1985-02-01

Kinetic and electrophysiological studies were carried out in the in vitro Rana esculenta skin, bathed in dilute sodium solution, to characterize the proton pump and coupling between sodium absorption (JNa+n) and proton excretion (JH+n). JNa+n and JH+n were both dependent on transepithelial potential (psi ms); hyperpolarizing the skin decreased JNa+n and increased JH+n; depolarization produced the opposite effects. Amiloride (5 X 10(-5) M) at a clamped psi ms of +50 mV inhibited JNa+n without affecting JH+n. Variations of psi ms or pH had identical effects on JH+n. Ethoxzolamide inhibited JH+n and simultaneously increased psi ms by 15-30 mV. These changes were accompanied by depolarization of the apical membrane potential psi mc from -47 to -25 mV and an increase in apical membrane resistance of 30%; no significant effects on basolateral membrane potential (psi cs) and resistance (Rb) nor on shunt resistance (Rj) were observed. The proton pump appears to be localized at the apical membrane. The proton pump was also inhibited by deoxygenation, oligomycin, dicyclohexylcarbodiimide and vanadate (100, 78, 83 and 100% inhibition respectively). The variations of JH+n and of the measured electrical currents were significantly correlated. These findings are supportive evidence of a primary active proton pump, electrogenic and strictly linked to aerobic metabolism. The current-voltage (I-V) relation of the proton pump was obtained as the difference in the I-V curves of the apical membrane extracted before and after proton-pump inhibition by ethoxzolamide during amiloride block of sodium transport. The proton-pump current (IP) was best described by a saturable exponential function of psi mc. Maximal pump current (ImaxP) was calculated to be 200 nequiv h-1 cm-2 at a psi mc of +50 mV and the pump reversal potential ERP was -130 mV. The effect of ethoxzolamide to depolarize psi mc was dependent on the relation between psi mc and ERP. Maximal induced depolarization occurred at a psi mc of +50 mV whereas ethoxzolamide exerted minimal effect on psi mc when the ERP was approached either by voltage clamping the apical membrane or by the addition of amiloride. We show that electroneutral sodium-proton countertransport is not the mechanism of active proton excretion in frog skin but that it is the proton excretion which provides a favourable electrical driving force for passive apical sodium entry.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrogenic active proton pump in Rana esculenta skin and its role in sodium ion transport.

PubMed Central

Ehrenfeld, J; Garcia-Romeu, F; Harvey, B J

1985-01-01

Kinetic and electrophysiological studies were carried out in the in vitro Rana esculenta skin, bathed in dilute sodium solution, to characterize the proton pump and coupling between sodium absorption (JNa+n) and proton excretion (JH+n). JNa+n and JH+n were both dependent on transepithelial potential (psi ms); hyperpolarizing the skin decreased JNa+n and increased JH+n; depolarization produced the opposite effects. Amiloride (5 X 10(-5) M) at a clamped psi ms of +50 mV inhibited JNa+n without affecting JH+n. Variations of psi ms or pH had identical effects on JH+n. Ethoxzolamide inhibited JH+n and simultaneously increased psi ms by 15-30 mV. These changes were accompanied by depolarization of the apical membrane potential psi mc from -47 to -25 mV and an increase in apical membrane resistance of 30%; no significant effects on basolateral membrane potential (psi cs) and resistance (Rb) nor on shunt resistance (Rj) were observed. The proton pump appears to be localized at the apical membrane. The proton pump was also inhibited by deoxygenation, oligomycin, dicyclohexylcarbodiimide and vanadate (100, 78, 83 and 100% inhibition respectively). The variations of JH+n and of the measured electrical currents were significantly correlated. These findings are supportive evidence of a primary active proton pump, electrogenic and strictly linked to aerobic metabolism. The current-voltage (I-V) relation of the proton pump was obtained as the difference in the I-V curves of the apical membrane extracted before and after proton-pump inhibition by ethoxzolamide during amiloride block of sodium transport. The proton-pump current (IP) was best described by a saturable exponential function of psi mc. Maximal pump current (ImaxP) was calculated to be 200 nequiv h-1 cm-2 at a psi mc of +50 mV and the pump reversal potential ERP was -130 mV. The effect of ethoxzolamide to depolarize psi mc was dependent on the relation between psi mc and ERP. Maximal induced depolarization occurred at a psi mc of +50 mV whereas ethoxzolamide exerted minimal effect on psi mc when the ERP was approached either by voltage clamping the apical membrane or by the addition of amiloride. We show that electroneutral sodium-proton countertransport is not the mechanism of active proton excretion in frog skin but that it is the proton excretion which provides a favourable electrical driving force for passive apical sodium entry.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 6 Fig. 7 PMID:2582114

PROTON HEATING BY PICK-UP ION DRIVEN CYCLOTRON WAVES IN THE OUTER HELIOSPHERE: HYBRID EXPANDING BOX SIMULATIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hellinger, Petr; Trávníček, Pavel M., E-mail: petr.hellinger@asu.cas.cz

Using a one-dimensional hybrid expanding box model, we investigate properties of the solar wind in the outer heliosphere. We assume a proton–electron plasma with a strictly transverse ambient magnetic field and, aside from the expansion, we take into account the influence of a continuous injection of cold pick-up protons through the charge-exchange process between the solar wind protons and hydrogen of interstellar origin. The injected cold pick-up protons form a ring distribution function, which rapidly becomes unstable, and generate Alfvén cyclotron waves. The Alfvén cyclotron waves scatter pick-up protons to a spherical shell distribution function that thickens over that timemore » owing to the expansion-driven cooling. The Alfvén cyclotron waves heat solar wind protons in the perpendicular direction (with respect to the ambient magnetic field) through cyclotron resonance. At later times, the Alfvén cyclotron waves become parametrically unstable and the generated ion-acoustic waves heat protons in the parallel direction through Landau resonance. The resulting heating of the solar wind protons is efficient on the expansion timescale.« less

Transient many-body instability in driven Dirac materials

NASA Astrophysics Data System (ADS)

Pertsova, Anna; Triola, Christopher; Balatsky, Alexander

The defining feature of a Dirac material (DM) is the presence of nodes in the low-energy excitation spectrum leading to a strong energy dependence of the density of states (DOS). The vanishing of the DOS at the nodal point implies a very low effective coupling constant which leads to stability of the node against electron-electron interactions. Non-equilibrium or driven DM, in which the DOS and hence the effective coupling can be controlled by external drive, offer a new platform for investigating collective instabilities. In this work, we discuss the possibility of realizing transient collective states in driven DMs. Motivated by recent pump-probe experiments which demonstrate the existence of long-lived photo-excited states in DMs, we consider an example of a transient excitonic instability in an optically-pumped DM. We identify experimental signatures of the transient excitonic condensate and provide estimates of the critical temperatures and lifetimes of these states for few important examples of DMs, such as single-layer graphene and topological-insulator surfaces.

Excitonic gap formation in pumped Dirac materials

NASA Astrophysics Data System (ADS)

Triola, Christopher; Pertsova, Anna; Markiewicz, Robert S.; Balatsky, Alexander V.

2017-05-01

Recent pump-probe experiments demonstrate the possibility that Dirac materials may be driven into transient excited states describable by two chemical potentials, one for the electrons and one for the holes. Given the Dirac nature of the spectrum, such an inverted population allows the optical tunability of the density of states of the electrons and holes, effectively offering control of the strength of the Coulomb interaction. Here we discuss the feasibility of realizing transient excitonic instabilities in optically pumped Dirac materials. We demonstrate, theoretically, the reduction of the critical coupling leading to the formation of a transient condensate of electron-hole pairs and identify signatures of this state. Furthermore, we provide guidelines for experiments by both identifying the regimes in which such exotic many-body states are more likely to be observed and estimating the magnitude of the excitonic gap for a few important examples of existing Dirac materials. We find a set of material parameters for which our theory predicts large gaps and high critical temperatures and which could be realized in future Dirac materials. We also comment on transient excitonic instabilities in three-dimensional Dirac and Weyl semimetals. This study provides an example of a transient collective instability in driven Dirac materials.

Light-energy conversion in engineered microorganisms.

PubMed

Johnson, Ethan T; Schmidt-Dannert, Claudia

2008-12-01

Increasing interest in renewable resources by the energy and chemical industries has spurred new technologies both to capture solar energy and to develop biologically derived chemical feedstocks and fuels. Advances in molecular biology and metabolic engineering have provided new insights and techniques for increasing biomass and biohydrogen production, and recent efforts in synthetic biology have demonstrated that complex regulatory and metabolic networks can be designed and engineered in microorganisms. Here, we explore how light-driven processes may be incorporated into nonphotosynthetic microbes to boost metabolic capacity for the production of industrial and fine chemicals. Progress towards the introduction of light-driven proton pumping or anoxygenic photosynthesis into Escherichia coli to increase the efficiency of metabolically-engineered biosynthetic pathways is highlighted.

Rabeprazole: the role of proton pump inhibitors in Helicobacter pylori eradication.

PubMed

Sharara, Ala I

2005-12-01

Proton pump inhibitors have become one of the cornerstones in the treatment of Helicobacter pylori infection. Rabeprazole (Pariet) is a substituted benzimidazole proton pump inhibitor with potent gastric acid suppression properties. Its high acid-base dissociation constant allows activation over a broader pH range, resulting in quick, irreversible binding to the H+/K+-ATPase pump, and a more rapid onset of action compared with omeprazole, lansoprazole and pantoprazole. Unlike other proton pump inhibitors, the metabolism of rabeprazole is primarily via a nonenzymatic reduction to the thioether derivative, and the cytochrome P450 isoenzyme 2C19 is only partly involved in its metabolism. The effect of genetic polymorphism in cytochrome P450 isoenzyme 2C19 on the pharmacokinetics and pharmacodynamics of rabeprazole is therefore limited. In humans, once-daily dosing of 5-40 mg of rabeprazole inhibits gastric acid secretion in a dose-dependent manner. In vitro studies have shown that rabeprazole possesses more potent antibacterial properties against the growth of H. pylori than other proton pump inhibitors. Furthermore, its thioether derivative has more potent inhibitory in vitro activity against the growth and motility of clarithromycin-resistant H. pylori than other proton pump inhibitors or commonly used antimicrobials. Despite these inherent favorable characteristics of rabeprazole, randomized controlled trials have largely shown equivalence amongst proton pump inhibitors when used with two antibiotics in the eradication of H. pylori, with cure rates of 75-89% on an intent-to-treat basis. However, rabeprazole appears to consistently achieve such comparable eradication rates even when used at reduced doses (10 mg twice daily) as part of clarithromycin-based triple therapy.

The role of the pharmacist in the selection and use of over-the-counter proton-pump inhibitors.

PubMed

Boardman, Helen F; Heeley, Gordon

2015-10-01

Heartburn and other symptoms of gastro-oesophageal reflux occur in ~30% of survey respondents in multiple countries worldwide. Heartburn and acid regurgitation are common complaints in the pharmacy, where patients frequently seek relief through medication and advice. The growing number of proton-pump inhibitors available in the over-the-counter setting provides an efficacious choice to patients experiencing frequent heartburn. Pharmacists can assist patients in their treatment decisions whilst inquiring about alarm symptoms that should prompt a physician referral. Aim of the review Provide pharmacists with a review of current clinical research and expert guidelines on use of over-the-counter proton-pump inhibitors. This narrative review was conducted to identify publications relevant to the following themes: overview of available treatments for frequent episodes of heartburn/acid regurgitation; treatment algorithms providing guidance on when to use over-the-counter proton-pump inhibitors; and the role of the pharmacist in the use of over-the-counter proton-pump inhibitors. Frequent symptoms of acid reflux, such as heartburn and acid regurgitation, can interfere substantially with daily life activities. Proton-pump inhibitors are the most efficacious treatment for frequent reflux symptoms and are recommended as an appropriate initial treatment in uncomplicated cases. Proton-pump inhibitors have varying pharmacokinetics and pharmacodynamics across the class; 20 mg esomeprazole has higher bioavailability and exposure than over-the-counter omeprazole, for example. However, differences in clinical efficacy for symptom relief have not been demonstrated. The safety and tolerability of proton-pump inhibitors have been well established in clinical trial and post-marketing settings, and use of a short regimen is associated with a very low likelihood of missing a more serious condition. Pharmacists can assist patients with accurate self-diagnosis by asking short, simple questions to characterize the nature, severity, and frequency of symptoms. Additionally, pharmacists can inquire about alarm symptoms that should prompt referral to a physician. Pharmacists should inform those patients for whom over-the-counter proton-pump inhibitors are appropriate on their proper use. Over-the-counter proton-pump inhibitors have a valuable role in the treatment of frequent heartburn. Pharmacists have the opportunity to guide patients through selection of the best treatment option for their symptoms.

Sulfide-dependent photosynthetic electron flow coupled to proton translocation in thylakoids of the cyanobacterium Oscillatoria limnetica.

PubMed

Shahak, Y; Arieli, B; Binder, B; Padan, E

1987-12-01

Light-induced proton translocation coupled to sulfide-dependent electron transport has been studied in isolated thylakoids of the cyanobacterium Oscillatoria limnetica. The thylakoids are obtained by osmotic shock of washed spheroplasts, prepared with glycine-betaine as the osmotic stabilizer. 13C NMR studies suggests that betaine is the major osmoregulator in O. limnetica. Thylakoid preparations obtained from both sulfide-induced anoxygenic cells and noninduced oxygenic cells are capable of proton pumping coupled to phenazinemethosulfate-mediated cyclic electron flow. However, only in the induced thylakoids can sulfide-dependent proton gradient (delta pH) formation be measured, using either NADP or methyl viologen as the terminal acceptor. Sulfide-dependent delta pH formation correlates with a high-affinity electron donation site (apparent Km 44 microM at pH 7.9). This site is not lost upon washing of the thylakoids. In addition, both sulfide-dependent electron transport and delta pH formation are sensitive to inhibitors of the cytochrome b6f complex such as 2-n-nonyl-4-hydroxyquinoline-N-oxide, 2,4-dinitrophenyl ether of 2-iodo-4-nitrothymol, or stigmatellin. Sulfide-dependent NADP photoreduction of low affinity (which does not saturate by as much as 7 mM sulfide) is detected in both induced and noninduced thylakoids, but this activity is insensitive to the inhibitors and is not coupled to proton transport. It is suggested that the adaptation of O. limnetica to anoxygenic photosynthesis involves the induction of a thylakoid factor(s) which creates a high-affinity site for sulfide, and the transfer of its electrons via the cytochrome b6f complex, coupled to proton translocation.

Ultrafast dynamics of isolated model photoactive yellow protein chromophores: "Chemical perturbation theory" in the laboratory.

PubMed

Vengris, Mikas; Larsen, Delmar S; van der Horst, Michael A; Larsen, Olaf F A; Hellingwerf, Klaas J; van Grondelle, Rienk

2005-03-10

Pump-probe and pump-dump probe experiments have been performed on several isolated model chromophores of the photoactive yellow protein (PYP). The observed transient absorption spectra are discussed in terms of the spectral signatures ascribed to solvation, excited-state twisting, and vibrational relaxation. It is observed that the protonation state has a profound effect on the excited-state lifetime of p-coumaric acid. Pigments with ester groups on the coumaryl tail end and charged phenolic moieties show dynamics that are significantly different from those of other pigments. Here, an unrelaxed ground-state intermediate could be observed in pump-probe signals. A similar intermediate could be identified in the sinapinic acid and in isomerization-locked chromophores by means of pump-dump probe spectroscopy; however, in these compounds it is less pronounced and could be due to ground-state solvation and/or vibrational relaxation. Because of strong protonation-state dependencies and the effect of electron donor groups, it is argued that charge redistribution upon excitation determines the twisting reaction pathway, possibly through interaction with the environment. It is suggested that the same pathway may be responsible for the initiation of the photocycle in native PYP.

Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps

PubMed Central

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:24688018

Remotely powered distributed microfluidic pumps and mixers based on miniature diodes.

PubMed

Chang, Suk Tai; Beaumont, Erin; Petsev, Dimiter N; Velev, Orlin D

2008-01-01

We demonstrate new principles of microfluidic pumping and mixing by electronic components integrated into a microfluidic chip. The miniature diodes embedded into the microchannel walls rectify the voltage induced between their electrodes from an external alternating electric field. The resulting electroosmotic flows, developed in the vicinity of the diode surfaces, were utilized for pumping or mixing of the fluid in the microfluidic channel. The flow velocity of liquid pumped by the diodes facing in the same direction linearly increased with the magnitude of the applied voltage and the pumping direction could be controlled by the pH of the solutions. The transverse flow driven by the localized electroosmotic flux between diodes oriented oppositely on the microchannel was used in microfluidic mixers. The experimental results were interpreted by numerical simulations of the electrohydrodynamic flows. The techniques may be used in novel actively controlled microfluidic-electronic chips.

Effect of the Prophylactic Use of Proton-Pump Inhibitors on the Pattern of Gastrointestinal Symptoms in Patients Late After Kidney Transplant.

PubMed

Królikowski, Jerzy; Pawłowicz, Ewa; Budzisz, Ewa; Nowicki, Michał

2016-10-01

Although immunosuppressive drugs have been recognized as leading causes of gastrointestinal symptoms after kidney transplant, other widely used medications such as proton-pump inhibitors recently have been implicated. Our aim was to study the effects of chronic proton-pump inhibitor therapy on gastrointestinal symptoms in clinically stable patients late after kidney transplant. The study comprised 100 kidney transplant recipients (66 men and 34 women, mean age of 49 ± 12 y, mean time after transplant of 56 ± 46 mo). All patients completed the Gastrointestinal Symptoms Rating Scale and the Quality of Life Questionnaire SF-8 surveys. The most commonly reported symptoms included borborygmus (27%), flatulence (23%), abdominal distension (18%), urgent need of defecation (17%), and heartburn, acid reflux, and eructation (13%). Proton-pump inhibitors were chronically used by 50% of patients and sporadically by 33%. Gastrointestinal Symptoms Rating Scale scores were higher in patients who used proton-pump inhibitors (mean score of 7.8 ± 5.5 vs 4.6 ± 3.0; P = .013). Total score of items representing diarrhea in the Gastrointestinal Symptoms Rating Scale (increased passage of stools, loose stools, urgent need of defecation, incomplete evacuation) was higher in patients treated with proton-pump inhibitors than in those not treated (2.3 ± 2.2 vs 1.3 ± 1.9; P = .04). Chronic use of proton-pump inhibitors may increase the prevalence of gastrointestinal symptoms, particularly diarrhea, in patients late after kidney transplant.

Tautomeric selectivity of the excited-state lifetime of guanine/cytosine base pairs: The role of electron-driven proton-transfer processes

PubMed Central

Sobolewski, Andrzej L.; Domcke, Wolfgang; Hättig, C.

2005-01-01

The UV spectra of three different conformers of the guanine/cytosine base pair were recorded recently with UV-IR double-resonance techniques in a supersonic jet [Abo-Riziq, A., Grace, L., Nir, E., Kabelac, M., Hobza, P. & de Vries, M. S. (2005) Proc. Natl. Acad. Sci. USA 102, 20–23]. The spectra provide evidence for a very efficient excited-state deactivation mechanism that is specific for the Watson–Crick structure and may be essential for the photostability of DNA. Here we report results of ab initio electronic-structure calculations for the excited electronic states of the three lowest-energy conformers of the guanine/cytosine base pair. The calculations reveal that electron-driven interbase proton-transfer processes play an important role in the photochemistry of these systems. The exceptionally short lifetime of the UV-absorbing states of the Watson–Crick conformer is tentatively explained by the existence of a barrierless reaction path that connects the spectroscopic 1π π * excited state with the electronic ground state via two electronic curve crossings. For the non-Watson–Crick structures, the photochemically reactive state is located at higher energies, resulting in a barrier for proton transfer and, thus, a longer lifetime of the UV-absorbing 1π π * state. The computational results support the conjecture that the photochemistry of hydrogen bonds plays a decisive role for the photostability of the molecular encoding of the genetic information in isolated DNA base pairs. PMID:16330778

Impact of a pharmacist-driven protocol to decrease proton pump inhibitor use in non-intensive care hospitalized adults.

PubMed

Michal, Jessica; Henry, Thomas; Street, Connie

2016-09-01

Results of a pharmacist-driven protocol to decrease proton pump inhibitor (PPI) use in non-intensive care unit (ICU) hospitalized adults are presented. This concurrent preintervention and postintervention study included subjects at least 18 years of age receiving PPIs while hospitalized in general medical or surgical beds. Patients were identified for inclusion in the postintervention group using a daily list of hospitalized patients with active PPI orders. A pharmacist evaluated these subjects for PPI appropriateness, and then recommended discontinuing or changing PPIs to histamine H2-receptor antagonists. Per protocol, the pharmacist could change PPIs to H2-antagonists if prescribers did not respond to recommendations. Preintervention group patients were gathered retrospectively and treated as the retrospective control group. Patients were excluded if they had cumulative ICU or ICU step-down stays of at least two days, had predefined appropriate indications for PPIs, or were not evaluated within one day of PPI orders. The primary outcome was the rate of PPI use. Secondary objectives included rates of prescriber acceptance of pharmacist recommendations and hospital-onset Clostridium difficile infections (HO-CDI). PPIs were discontinued in 66.0% (n = 62) of postintervention group patients compared to 41.1% (n = 39) of the preintervention group (absolute risk reduction, 24.9%; p = 0.001). In the postintervention group, 31.9% (n = 30) of recommendations were accepted, whereas 11.7% (n = 11) were rejected. No subjects in either group were diagnosed with HO-CDI during the study period. The pharmacist-driven protocol described in this study decreased PPI use in non-ICU hospitalized adults. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Optical silencing of body wall muscles induces pumping inhibition in Caenorhabditis elegans

PubMed Central

Takahashi, Megumi

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 activation of Arch or ACR2 with light illumination, and recovers gradually after terminating illumination. Pumping was similarly inhibited by illumination in locomotion-defective mutants carrying Arch, suggesting that perturbation of locomotory movement is not critical for pumping inhibition. Analysis of mutants and cell ablation experiments showed that the signals mediating the pumping inhibition response triggered by activation of Arch with weak light are transferred mainly through two pathways: one involving gap junction-dependent mechanisms through pharyngeal I1 neurons, which mediate fast signals, and the other involving dense-core vesicle-dependent mechanisms, which mediate slow signals. Activation of Arch with strong light inhibited pumping strongly in a manner that does not rely on either gap junction-dependent or dense-core vesicle-dependent mechanisms. Our study revealed a new aspect of the neural and neuroendocrine controls of pumping initiated from the body wall muscles. PMID:29281635

Gigahertz single-electron pumping in silicon with an accuracy better than 9.2 parts in 10{sup 7}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamahata, Gento, E-mail: yamahata.gento@lab.ntt.co.jp; Karasawa, Takeshi; Fujiwara, Akira

2016-07-04

High-speed and high-accuracy pumping of a single electron is crucial for realizing an accurate current source, which is a promising candidate for a quantum current standard. Here, using a high-accuracy measurement system traceable to primary standards, we evaluate the accuracy of a Si tunable-barrier single-electron pump driven by a single sinusoidal signal. The pump operates at frequencies up to 6.5 GHz, producing a current of more than 1 nA. At 1 GHz, the current plateau with a level of about 160 pA is found to be accurate to better than 0.92 ppm (parts per million), which is a record value for 1-GHz operation. At 2 GHz,more » the current plateau offset from 1ef (∼320 pA) by 20 ppm is observed. The current quantization accuracy is improved by applying a magnetic field of 14 T, and we observe a current level of 1ef with an accuracy of a few ppm. The presented gigahertz single-electron pumping with a high accuracy is an important step towards a metrological current standard.« less

Stimulated Mirror Instability From the Interplay of Anisotropic Protons and Electrons, and their Suprathermal Populations

NASA Astrophysics Data System (ADS)

Shaaban, S. M.; Lazar, M.; Astfalk, P.; Poedts, S.

2018-03-01

Mirror instability driven by the temperature anisotropy of protons can offer a plausible explanation for the mirror-like fluctuations observed in planetary magnetosheaths. In the present paper we invoke a realistic kinetic approach which can reproduce nonthermal features of plasma particles reported by the observations, i.e., temperature anisotropies and suprathermal populations. Seeking accuracy, a numerical analysis is performed using an advanced code named DSHARK, recently proposed to resolve the linear dispersion and stability for an arbitrary propagation in bi-Kappa distributed electron-proton plasmas. The stimulating effect of the anisotropic bi-Maxwellian electrons reported in Remya et al. (2013, https://doi.org/10.1002/jgra.50091) is markedly enhanced in the presence of suprathermal electrons described by the bi-Kappa distribution functions. The influence of suprathermal protons is more temperate, but overall, present results demonstrate that these sources of free energy provide natural conditions for a stimulated mirror instability, more efficient than predicted before and capable to compete with other instabilities (e.g., the electromagnetic ion-cyclotron instability) and mechanisms of relaxation.

Weibel instability mediated collisionless shocks using intense laser-driven plasmas

NASA Astrophysics Data System (ADS)

Palaniyappan, Sasi; Huang, Chengkun; Gautier, Donald; Fernandez, Juan; Ma, Wenjun; Schreiber, Jorg; LANL Collaboration; LMU Team

2016-10-01

The origin of cosmic rays remains a long-standing challenge in astrophysics and continues to fascinate physicists. It is believed that ``collisionless shocks'' - where the particle Coulomb mean free path is much larger that the shock transition - are a dominant source of energetic cosmic rays. These shocks are ubiquitous in astrophysical environments such as gamma-ray bursts, supernova remnants, pulsar wind nebula and coronal mass ejections from the sun. Several spacecraft observations have revealed acceleration of charged particles, mostly electrons, to very high energies with in the shock front. There is now also clear observational evidence that supernova remnant shocks accelerate both protons and electrons. The understanding of the microphysics behind collisionless shocks and their particle acceleration is tightly related with nonlinear basic plasma processes and remains a grand challenge. In this poster, we will present results from recent experiments at the LANL Trident laser facility studying collisionless shocks using intense ps laser (80J, 650 fs - peak intensity of 1020 W/cm2) driven near-critical plasmas using carbon nanotube foam targets. A second short pulse laser driven protons from few microns thick aluminum foil is used to image the laser-driven plasma.

Molecular alignment effect on the photoassociation process via a pump-dump scheme.

PubMed

Wang, Bin-Bin; Han, Yong-Chang; Cong, Shu-Lin

2015-09-07

The photoassociation processes via the pump-dump scheme for the heternuclear (Na + H → NaH) and the homonuclear (Na + Na → Na2) molecular systems are studied, respectively, using the time-dependent quantum wavepacket method. For both systems, the initial atom pair in the continuum of the ground electronic state (X(1)Σ(+)) is associated into the molecule in the bound states of the excited state (A(1)Σ(+)) by the pump pulse. Then driven by a time-delayed dumping pulse, the prepared excited-state molecule can be transferred to the bound states of the ground electronic state. It is found that the pump process can induce a superposition of the rovibrational levels |v, j〉 on the excited state, which can lead to the field-free alignment of the excited-state molecule. The molecular alignment can affect the dumping process by varying the effective coupling intensity between the two electronic states or by varying the population transfer pathways. As a result, the final population transferred to the bound states of the ground electronic state varies periodically with the delay time of the dumping pulse.

Molecular alignment effect on the photoassociation process via a pump-dump scheme

NASA Astrophysics Data System (ADS)

Wang, Bin-Bin; Han, Yong-Chang; Cong, Shu-Lin

2015-09-01

The photoassociation processes via the pump-dump scheme for the heternuclear (Na + H → NaH) and the homonuclear (Na + Na → Na2) molecular systems are studied, respectively, using the time-dependent quantum wavepacket method. For both systems, the initial atom pair in the continuum of the ground electronic state (X1Σ+) is associated into the molecule in the bound states of the excited state (A1Σ+) by the pump pulse. Then driven by a time-delayed dumping pulse, the prepared excited-state molecule can be transferred to the bound states of the ground electronic state. It is found that the pump process can induce a superposition of the rovibrational levels |v, j> on the excited state, which can lead to the field-free alignment of the excited-state molecule. The molecular alignment can affect the dumping process by varying the effective coupling intensity between the two electronic states or by varying the population transfer pathways. As a result, the final population transferred to the bound states of the ground electronic state varies periodically with the delay time of the dumping pulse.

Prompt particle acceleration around moving X-point magnetic field during impulsive phase of solar flares

NASA Technical Reports Server (NTRS)

Sakai, Jun-Ichi

1992-01-01

We present a model for high-energy solar flares to explain prompt proton and electron acceleration, which occurs around moving X-point magnetic field during the implosion phase of the current sheet. We derive the electromagnetic fields during the strong implosion phase of the current sheets, which is driven by the converging flow derived from the magnetohydrodynamic equations. It is shown that both protons and electrons can be promptly (within 1 second) accelerated to approximately 70 MeV and approximately 200 MeV, respectively. This acceleration mechanism can be applicable for the impulsive phase of the gradual gamma ray and proton flares (gradual GR/P flare), which have been called two-ribbon flares.

An antilock molecular braking system.

PubMed

Sun, Wei-Ting; Huang, Shou-Ling; Yao, Hsuan-Hsiao; Chen, I-Chia; Lin, Ying-Chih; Yang, Jye-Shane

2012-08-17

A light-driven molecular brake displaying an antilock function is constructed by introducing a nonradiative photoinduced electron transfer (PET) decay channel to compete with the trans (brake-off) → cis (brake-on) photoisomerization. A fast release of the brake can be achieved by deactivating the PET process through addition of protons. The cycle of irradiation-protonation-irradiation-deprotonation conducts the brake function and mimics the antilock braking system (ABS) of vehicles.

Role of protons in the pump cycle of KdpFABC investigated by time-resolved kinetic experiments.

PubMed

Damnjanovic, Bojana; Apell, Hans-Jürgen

2014-05-20

The time-resolved kinetics of the KdpFABC complex solubilized in Aminoxide WS-35 was investigated by ATP concentration jump experiments. ATP was photoreleased from its inactive precursor, caged ATP, and charge movements in the membrane domain of the KdpFABC were detected by the electrochromic dye RH421. At low ATP concentrations, the ATP binding step became rate-limiting with an apparent, pH-independent ATP binding affinity of ~70 μM. At saturating ATP concentrations, the rate-limiting step is the conformational transition (E1-P → P-E2) with a rate constant of ~1.7 s(-1) at 20 °C that was independent of K(+) concentration. This observation together with the detected fluorescence decrease indicates that K(+) (or another positive ion) is bound in the membrane domain after enzyme phosphorylation and the conformational transition to the P-E2 state. pH dependence experiments revealed different roles of H(+) in the transport mechanism. Two different functions of protons for the ion pump must be distinguished. On one hand, there are electrogenically bound "functional" protons, which are not transported but prerequisite for the performance of the ATP-driven half-cycle. On the other hand, protons bind to the transport sites, acting as weak congeners of K(+). There possibly are noncompetitively bound protons, affecting the enzyme activity and/or coupling between KdpA and KdpB subunits. Finally, the recently proposed Post-Albers model for the KdpFABC complex was supplemented with stoichiometry factors of 2 for K(+) and 3 for H(+), and additional inhibitory side reactions controlled by H(+) were introduced, which are relevant at pH <6.5 and/or in the absence of K(+).

Geometrical Optimization Approach to Isomerization: Models and Limitations.

PubMed

Chang, Bo Y; Shin, Seokmin; Engel, Volker; Sola, Ignacio R

2017-11-02

We study laser-driven isomerization reactions through an excited electronic state using the recently developed Geometrical Optimization procedure. Our goal is to analyze whether an initial wave packet in the ground state, with optimized amplitudes and phases, can be used to enhance the yield of the reaction at faster rates, driven by a single picosecond pulse or a pair of femtosecond pulses resonant with the electronic transition. We show that the symmetry of the system imposes limitations in the optimization procedure, such that the method rediscovers the pump-dump mechanism.

Enhanced Laser-Driven Ion Acceleration by Superponderomotive Electrons Generated from Near-Critical-Density Plasma

NASA Astrophysics Data System (ADS)

Bin, J. H.; Yeung, M.; Gong, Z.; Wang, H. Y.; Kreuzer, C.; Zhou, M. L.; Streeter, M. J. V.; Foster, P. S.; Cousens, S.; Dromey, B.; Meyer-ter-Vehn, J.; Zepf, M.; Schreiber, J.

2018-02-01

We report on the experimental studies of laser driven ion acceleration from a double-layer target where a near-critical density target with a few-micron thickness is coated in front of a nanometer-thin diamondlike carbon foil. A significant enhancement of proton maximum energies from 12 to ˜30 MeV is observed when a relativistic laser pulse impinges on the double-layer target under linear polarization. We attributed the enhanced acceleration to superponderomotive electrons that were simultaneously measured in the experiments with energies far beyond the free-electron ponderomotive limit. Our interpretation is supported by two-dimensional simulation results.

Transient Resonance Raman Spectroscopy of a Light-Driven Sodium-Ion-Pump Rhodopsin from Indibacter alkaliphilus.

PubMed

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.

Functional and evolutionary relationships between bacteriorhodopsin and halorhodopsin in the archaebacterium, halobacterium halobium

NASA Technical Reports Server (NTRS)

Lanyi, J. K.

1986-01-01

The archaebacteria occupy a unique place in phylogenetic trees constructed from analyses of sequences from key informational macromolecules, and their study continues to yield interesting ideas on the early evolution and divergence of biological forms. It is now known that the halobacteria among these species contain various retinal-proteins, resembling eukaryotic rhodopsins, but with different functions. Two of these pigments, located in the cytoplasmic membranes of the bacteria, are bacteriorhodopsin (a light-driven proton pump) and halorhodopsin (a light-driven chloride pump). Comparison of these systems is expected to reveal structure/function relationships in these simple (primitive?) energy transducing membrane components and evolutionary relationships which had produced the structural features which allow the divergent functions. Findings indicate that very different primary structures are needed for these proteins to accomplish their different functions. Indeed, analysis of partial amino acid sequences from halo-opsin shows already that few if any long segments exist which are homologous to bacterio-opsin. Either these proteins diverged a very long time ago to allow for the observed differences, or the evolutionary clock in the halobacteria runs faster than usual.

Electrostatic coupling of ion pumps.

PubMed

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.

Imaging and controlling proton motion in molecules

NASA Astrophysics Data System (ADS)

Ibrahim, H.; Beaulieu, S.; Wanie, V.; Endo, T.; Wales, B.; Tong, X.-M.; Schuurman, M. S.; Sanderson, J.; Légaré, F.

2017-11-01

How do atoms move within a molecule? What are the paths they take? Coulomb Explosion Imaging combined with a multi-color pump probe scheme allows us to address these questions with a table top setup. Since the momentum information of molecular fragments is preserved at the moment of explosion, we can deduce the fragment's momentary position, representing the structure of the molecule. We have studied isomerization and dissociation events through the movement of protons, deuterons and electrons, taking advantage of the rich statistics this technique provides. In the case of proton migration in the acetylene cation, we were able to identify an isotope dependent to- and fro isomerization behavior [1]. Presently, we are expanding our studies on more complex processes. Aside from passively studying dynamics, we have also actively controlled the electron localization in small molecules [2] using two-color mid-infrared asymmetric laser fields. The manipulation of protons, the lightest atomic fragments in molecules, is of great interest due to the tremendous diversity of molecules containing them, in combination with the generality of how protons behave within molecules. Their detection involves certain challenges since they move extremely fast compared to heavier atoms. Here, we focus on two different proton motions which are triggered by excitation with ultrashort laser pulses and imaged with the Coulomb explosion imaging (CEI) technique. First, we will discuss proton migration dynamics in the acetylene cation launched due to strong field multiphoton ionization with UV pulses in a rather simple table top approach. Second, we will concentrate on controlling electron localization - and thus proton localization - in the cation of the hydrogen molecule by using an asymmetric two color field in the mid-infrared (MIR).

Membrane Protein Incorporation into Nano-Bioelectronics: An insight into Rhodopsin Controlled SiNW-FET Devices

NASA Astrophysics Data System (ADS)

Tunuguntla, Ramya

Biological systems use different energy sources to interact with their environments by creating ion gradients, membrane electric potentials, or a proton motive force to accomplish strikingly complex tasks on the nanometer length scale, such as energy harvesting, and whole organism replication. Most of this activity involves a vast arsenal of active and passive ion channels, membrane receptors and ion pumps that mediate complex and precise transport across biological membranes. Despite the remarkable rate of progress exhibited by modern microelectronic devices, they still cannot compete with the efficiency and precision of biological systems on the component level. At the same time, the sophistication of these molecular machines provides an excellent opportunity to use them in hybrid bioelectronic devices where such a combination could deliver enhanced electronic functionality and enable seamless bi-directional interfaces between man-made and biological assemblies. Artificial membrane systems allow researchers to study the structure and function of membrane proteins in a matrix that approximates their natural environment and to integrate these proteins in ex-vivo devices such as electronic biosensors, thin-film protein arrays, or bio-fuel cells. Since most membrane proteins have vectorial functions, both functional studies and applications require effective control over protein orientation within a lipid bilayer. In our work, we have explored the role of the bilayer surface charge in determining transmembrane protein orientation and functionality during formation of proteoliposomes. We reconstituted a model vectorial ion pump, proteorhodopsin, in liposomes of opposite charges and varying charge densities and determined the resultant protein orientation. Antibody-binding assay and proteolysis of proteoliposomes showed physical evidence of preferential orientation, and functional assays verified vectorial nature of ion transport in this system. Our results indicate that the manipulation of lipid composition can indeed control orientation of an asymmetrically charged membrane protein, proteorhodopsin, in liposomes. One-dimensional inorganic nanostructures, which have critical dimensions comparable to the sizes of biological molecules, form an excellent materials platform for building such integrated structures. Researchers already use silicon nanowire-based field effect transistors functionalized with molecular recognition sites in a diverse array of biosensors. In our group, we have been developing a platform for integration of membrane protein functionality and electronic devices using a 1-D phospholipid bilayer device architecture. In these devices, the membrane proteins reside within the lipid bilayer that covers a nanowire channel of a field-effect transistor. This lipid bilayer performs several functions: it shields the nanowire from the solution species; it serves as a native-like environment for membrane proteins and preserves their functionality, integrity, and even vectorality. In this work, we show that a 1-D bilayer device incorporating a rhodopsin proton pump allows us to couple light-driven proton transport to a bioelectronic circuit. We also report that we were able to adapt another distinctive feature of biological signal processing---their widespread use of modifiers, co-factors, and mediator molecules---to regulate and fine-tune the operational characteristics of the bioelectronic device. In our example, we use co-assembly of protein channels and ionophores in the 1-D bilayer to modify the device output levels and response time.

Inhibitors of Proton Pumping

PubMed Central

Bisson, Mary A.

1986-01-01

Reported inhibitors of the Characean plasmalemma proton pump were tested for their ability to inhibit the passive H+ conductance which develops in Chara corallina Klein ex Willd. at high pH. Diethylstilbestrol inhibits the proton pump and the passive H+ conductance with about the same time course, at concentrations that have no effect on cytoplasmic streaming. N-Ethylmaleimide, a sulfhydryl reagent which is small and relatively nonpolar, also inhibits both pumping and passive conductance of H+. However, it also inhibits cytoplasmic streaming with about the same time course, and therefore could not be considered a specific ATPase inhibitor. p-Chloromercuribenzene sulfonate (PCMBS), a sulfhydryl reagent which is large and charged and hence less able to penetrate the membrane, does not inhibit pumping or conductance at low concentration. At high concentration, PCMBS sometimes inhibits pumping without affecting H+ conductance, but since streaming is also inhibited, the effect on the pump cannot be said to be specific. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide, a water soluble carbodiimide, weakly inhibits both pump and conductance, apparently specifically. PMID:16664807

Gating of proton and water transfer in the respiratory enzyme cytochrome c oxidase.

PubMed

Wikström, Mårten; Ribacka, Camilla; Molin, Mika; Laakkonen, Liisa; Verkhovsky, Michael; Puustinen, Anne

2005-07-26

The membrane-bound enzyme cytochrome c oxidase is responsible for cell respiration in aerobic organisms and conserves free energy from O2 reduction into an electrochemical proton gradient by coupling the redox reaction to proton-pumping across the membrane. O2 reduction produces water at the bimetallic heme a3/CuB active site next to a hydrophobic cavity deep within the membrane. Water molecules in this cavity have been suggested to play an important role in the proton-pumping mechanism. Here, we show by molecular dynamics simulations that the conserved arginine/heme a3 delta-propionate ion pair provides a gate, which exhibits reversible thermal opening that is governed by the redox state and the water molecules in the cavity. An important role of this gate in the proton-pumping mechanism is supported by site-directed mutagenesis experiments. Transport of the product water out of the enzyme must be rigidly controlled to prevent water-mediated proton leaks that could compromise the proton-pumping function. Exit of product water is observed through the same arginine/propionate gate, which provides an explanation for the observed extraordinary spatial specificity of water expulsion from the enzyme.

Exchangers man the pumps: Functional interplay between proton pumps and proton-coupled Ca(2+) exchangers

USDA-ARS?s Scientific Manuscript database

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...

1-Arylsulfonyl-2-(Pyridylmethylsulfinyl) Benzimidazoles as New Proton Pump Inhibitor Prodrugs

PubMed Central

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 inhibitors and the risk of pneumonia: a comparison of cohort and self-controlled case series designs

PubMed Central

2013-01-01

Background To compare the results of a new-user cohort study design and the self-controlled case series (SCCS) design using the risk of hospitalisation for pneumonia in those dispensed proton pump inhibitors compared to those unexposed as a case study. Methods The Australian Government Department of Veterans’ Affairs administrative claims database was used. Exposure to proton pump inhibitors and hospitalisations for pneumonia were identified over a 4 year study period 01 Jul 2007 -30 Jun 2011. The same inclusion and exclusion criteria were applied to both studies, however, the SCCS study included subjects with a least one hospitalisation for pneumonia. Results There were 105,467 subjects included in the cohort study and 6775 in the SCCS. Both studies showed an increased risk of hospitalisations for pneumonia in the three defined risk periods following initiation of proton pump inhibitors compared to baseline. With the highest risk in the first 1 to 7 days (Cohort RR, 3.24; 95% CI (2.50, 4.19): SCCS: RR, 3.07; 95% CI (2.69, 3.50)). Conclusions This study has shown that the self-controlled case series method produces similar risk estimates to a new-users cohort study design when applied to the association of proton pump inhibitors and pneumonia. Exposure to a proton pump inhibitor increases the likelihood of being admitted to hospital for pneumonia, with the risk highest in the first week of treatment. PMID:23800078

Probing ultrafast proton induced dynamics in transparent dielectrics

NASA Astrophysics Data System (ADS)

Taylor, M.; Coughlan, M.; Nersisyan, G.; Senje, L.; Jung, D.; Currell, F.; Riley, D.; Lewis, C. L. S.; Zepf, M.; Dromey, B.

2018-05-01

A scheme has been developed permitting the spatial and temporal characterisation of ultrafast dynamics induced by laser driven proton bursts in transparent dielectrics. Advantage is taken of the high degree of synchronicity between the proton bursts generated during laser-foil target interactions and the probing laser to provide the basis for streaking of the dynamics. Relaxation times of electrons (<10‑12 s) are measured following swift excitation across the optical band gap for various glass samples. A temporal resolution of <500 fs is achieved demonstrating that these ultrafast dynamics can be characterized on a single-shot basis.

Protonation-state-Coupled Conformational Dynamics in Reaction Mechanisms of Channel and Pump Rhodopsins

DOE PAGES

Bondar, Ana-Nicoleta; Smith, Jeremy C.

2017-07-25

Channel and pump rhodopsins use energy from light absorbed by a covalently bound retinal chromophore to transport ions across membranes of microbial cells. Ion transfer steps, including proton transfer, can couple to changes in protein conformational dynamics and water positions. Although general principles of how microbial rhodopsins function are largely understood, key issues pertaining to reaction mechanisms remain unclear. Here, we compare the protonation-coupled dynamics of pump and channelrhodopsins, highlighting the roles that water dynamics, protein electrostatics and protein flexibility can have in ion transport mechanisms. We discuss observations supporting important functional roles of inter- and intra-helical carboxylate/hydroxyl hydrogen-bonding motifs.more » Specifically, we use the proton pump bacteriorhodopsin, the sodium pump KR2, channelrhodopsins and Anabaena sensory rhodopsin. We outline the usefulness of theoretic biophysics approaches to the study of retinal proteins, challenges in studying the hydrogen-bond dynamics of rhodopsin active sites, and implications for conformational coupling in membrane transporters.« less

Protonation-state-Coupled Conformational Dynamics in Reaction Mechanisms of Channel and Pump Rhodopsins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bondar, Ana-Nicoleta; Smith, Jeremy C.

Channel and pump rhodopsins use energy from light absorbed by a covalently bound retinal chromophore to transport ions across membranes of microbial cells. Ion transfer steps, including proton transfer, can couple to changes in protein conformational dynamics and water positions. Although general principles of how microbial rhodopsins function are largely understood, key issues pertaining to reaction mechanisms remain unclear. Here, we compare the protonation-coupled dynamics of pump and channelrhodopsins, highlighting the roles that water dynamics, protein electrostatics and protein flexibility can have in ion transport mechanisms. We discuss observations supporting important functional roles of inter- and intra-helical carboxylate/hydroxyl hydrogen-bonding motifs.more » Specifically, we use the proton pump bacteriorhodopsin, the sodium pump KR2, channelrhodopsins and Anabaena sensory rhodopsin. We outline the usefulness of theoretic biophysics approaches to the study of retinal proteins, challenges in studying the hydrogen-bond dynamics of rhodopsin active sites, and implications for conformational coupling in membrane transporters.« less

Molecular alignment effect on the photoassociation process via a pump-dump scheme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Bin-Bin; Han, Yong-Chang, E-mail: ychan@dlut.edu.cn; Cong, Shu-Lin

The photoassociation processes via the pump-dump scheme for the heternuclear (Na + H → NaH) and the homonuclear (Na + Na → Na{sub 2}) molecular systems are studied, respectively, using the time-dependent quantum wavepacket method. For both systems, the initial atom pair in the continuum of the ground electronic state (X{sup 1}Σ{sup +}) is associated into the molecule in the bound states of the excited state (A{sup 1}Σ{sup +}) by the pump pulse. Then driven by a time-delayed dumping pulse, the prepared excited-state molecule can be transferred to the bound states of the ground electronic state. It is found thatmore » the pump process can induce a superposition of the rovibrational levels |v, j〉 on the excited state, which can lead to the field-free alignment of the excited-state molecule. The molecular alignment can affect the dumping process by varying the effective coupling intensity between the two electronic states or by varying the population transfer pathways. As a result, the final population transferred to the bound states of the ground electronic state varies periodically with the delay time of the dumping pulse.« less

Electron Heating in Low-Mach-number Perpendicular Shocks. I. Heating Mechanism

NASA Astrophysics Data System (ADS)

Guo, Xinyi; Sironi, Lorenzo; Narayan, Ramesh

2017-12-01

Recent X-ray observations of merger shocks in galaxy clusters have shown that the postshock plasma has two temperatures, with the protons hotter than the electrons. By means of two-dimensional particle-in-cell simulations, we study the physics of electron irreversible heating in low-Mach-number perpendicular shocks, for a representative case with sonic Mach number of 3 and plasma beta of 16. We find that two basic ingredients are needed for electron entropy production: (1) an electron temperature anisotropy, induced by field amplification coupled to adiabatic invariance; and (2) a mechanism to break the electron adiabatic invariance itself. In shocks, field amplification occurs at two major sites: at the shock ramp, where density compression leads to an increase of the frozen-in field; and farther downstream, where the shock-driven proton temperature anisotropy generates strong proton cyclotron and mirror modes. The electron temperature anisotropy induced by field amplification exceeds the threshold of the electron whistler instability. The growth of whistler waves breaks the electron adiabatic invariance and allows for efficient entropy production. For our reference run, the postshock electron temperature exceeds the adiabatic expectation by ≃ 15 % , resulting in an electron-to-proton temperature ratio of ≃ 0.45. We find that the electron heating efficiency displays only a weak dependence on mass ratio (less than ≃ 30 % drop, as we increase the mass ratio from {m}i/{m}e=49 up to {m}i/{m}e=1600). We develop an analytical model of electron irreversible heating and show that it is in excellent agreement with our simulation results.

Capacitive beam position monitors for the low-β beam of the Chinese ADS proton linac

NASA Astrophysics Data System (ADS)

Zhang, Yong; Wu, Jun-Xia; Zhu, Guang-Yu; Jia, Huan; Xue, Zong-Heng; Zheng, Hai; Xie, Hong-Ming; Kang, Xin-Cai; He, Yuan; Li, Lin; Denard, Jean Claude

2016-02-01

Beam Position Monitors (BPMs) for the low-β beam of the Chinese Accelerator Driven Subcritical system (CADS) Proton linac are of the capacitive pick-up type. They provide higher output signals than that of the inductive type. This paper will describe the design and tests of the capacitive BPM system for the low-β proton linac, including the pick-ups, the test bench and the read-out electronics. The tests done with an actual proton beam show a good agreement between the measurements and the simulations in the time domain. Supported by National Natural Science Foundation of China (11405240) and “Western Light” Talents Training Program of Chinese Academy of Sciences

Recent study of beam stability in the PSR

NASA Astrophysics Data System (ADS)

Wang, T. S. F.; Cooper, R.; Fitzgerald, D.; Frankle, S.; Hardek, T.; Hutson, R.; Macek, R.; Ohmori, C.; Plum, M.; Thiessen, H.

1993-05-01

A fast transverse instability with beam loss has been observed in the 800 MeV Los Alamos Pro Ring (PSR) when the injected beam intensity reaches 2 - 4(10)(exp 13) protons per pulse. Previous observations indicate that the instability is most likely driven by electrons trapped within the proton beam. Theoretical study shown that beam leakage into the inter-bunch gap leads to electron trapping. Recent experiments were carried out by using the newly implemented 'pinger' and by varying the machine transition gamma to explore further the 'e-p' instability and the nature of the instability. This paper summarizes some of these recent experimental results and theoretical studies.

Four-wave mixing in an asymmetric double quantum dot molecule

NASA Astrophysics Data System (ADS)

Kosionis, Spyridon G.

2018-06-01

The four-wave mixing (FWM) effect of a weak probe field, in an asymmetric semiconductor double quantum dot (QD) structure driven by a strong pump field is theoretically studied. Similarly to the case of examining several other nonlinear optical processes, the nonlinear differential equations of the density matrix elements are used, under the rotating wave approximation. By suitably tuning the intensity and the frequency of the pump field as well as by changing the value of the applied bias voltage, a procedure used to properly adjust the electron tunneling coupling, we control the FWM in the same way as several other nonlinear optical processes of the system. While in the weak electron tunneling regime, the impact of the pump field intensity on the FWM is proven to be of crucial importance, for even higher rates of the electron tunneling it is evident that the intensity of the pump field has only a slight impact on the form of the FWM spectrum. The number of the spectral peaks, depends on the relation between specific parameters of the system.

Superluminescence from an optically pumped molecular tunneling junction by injection of plasmon induced hot electrons

PubMed Central

Braun, Kai; Wang, Xiao; Kern, Andreas M; Adler, Hilmar; Peisert, Heiko; Chassé, Thomas; Zhang, Dai

2015-01-01

Summary Here, we demonstrate a bias-driven superluminescent point light-source based on an optically pumped molecular junction (gold substrate/self-assembled molecular monolayer/gold tip) of a scanning tunneling microscope, operating at ambient conditions and providing almost three orders of magnitude higher electron-to-photon conversion efficiency than electroluminescence induced by inelastic tunneling without optical pumping. A positive, steadily increasing bias voltage induces a step-like rise of the Stokes shifted optical signal emitted from the junction. This emission is strongly attenuated by reversing the applied bias voltage. At high bias voltage, the emission intensity depends non-linearly on the optical pump power. The enhanced emission can be modelled by rate equations taking into account hole injection from the tip (anode) into the highest occupied orbital of the closest substrate-bound molecule (lower level) and radiative recombination with an electron from above the Fermi level (upper level), hence feeding photons back by stimulated emission resonant with the gap mode. The system reflects many essential features of a superluminescent light emitting diode. PMID:26171286

Electron dynamics and prompt ablation of aluminum surface excited by intense femtosecond laser pulse

NASA Astrophysics Data System (ADS)

Ionin, A. A.; Kudryashov, S. I.; Makarov, S. V.; Seleznev, L. V.; Sinitsyn, D. V.

2014-12-01

Thin aluminum film homogeneously heated by intense IR femtosecond laser pulses exhibits on the excitation timescale consequent fluence-dependent rise and drop of the IR-pump self-reflectivity, followed by its final saturation at higher fluences F > 0.3 J/cm2. This prompt optical dynamics correlates with the initial monotonic increase in the accompanying laser-induced electron emission, which is succeeded by its non-linear (three-photon) increase for F > 0.3 J/cm2. The underlying electronic dynamics is related to the initial saturation of IR resonant interband transitions in this material, followed by its strong instantaneous electronic heating via intraband transitions during the pump pulse resulting in thermionic emission. Above the threshold fluence of 0.3 J/cm2, the surface electronic heating is balanced during the pump pulse by simultaneous cooling via intense plasma removal (prompt ablation). The relationship between the deposited volume energy density in the film and its prompt electronic temperature derived from the self-reflection measurements using a Drude model, demonstrates a kind of electron "liquid-vapor" phase transition, driven by strong cubic optical non-linearity of the photo-excited aluminum.

Recent advances in chirally pure proton pump inhibitors.

PubMed

Pai, Vikas; Pai, Nitin

2007-08-01

Chirality is a ubiquitous natural phenomenon resulting because of a differential spatial orientation of molecules around its chiral centre. This leads to the existence of two or more spatially dissimilar forms, known as stereoisomers or enantiomers, which are non-superimposable images of each other and may significantly differ from each other with respect to pharmacokinetic and pharmacodynamic properties and molecular interaction. Thus one isomer may offer significant pharmacokinetic and therapeutic advantages as compared to the other isomer or the racemic mixture (mixture containing both enantiomers). Proton pump inhibitors are a class of drugs which have been very effective in the management of acid-related disorders. The proton pumps currently available in the market including omeprazole, pantoprazole, rabeprazole and lansoprazole are racemic mixtures of the S and R isomers. Chirally pure forms of proton pump inhibitors show a superior metabolic and pharmacokinetic profile as compared to their racemates. The therapeutic efficacy is also superior to the parent racemate. This has been clearly demonstrated with the development of esomeprazole- the S-isomer of omeprazole. S-pantoprazole and dexrabeprazole also offer therapeutic advantages as compared to racemic pantoprazole and racemic rabeprazole respectively. This article reviews the chiral developments in the proton pump inhibitors and their clinical applications.

Aspirin and omeprazole for secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers.

PubMed

García-Rayado, Guillermo; Sostres, Carlos; Lanas, Angel

2017-08-01

Cardiovascular disease is the most important cause of morbidity and mortality in the world and low-dose aspirin is considered the cornerstone of the cardiovascular disease prevention. However, low-dose aspirin use is associated with gastrointestinal adverse effects in the whole gastrointestinal tract. In this setting, co-therapy with a proton pump inhibitor is the most accepted strategy to reduce aspirin related upper gastrointestinal damage. In addition, some adverse effects have been described with proton pump inhibitors long term use. Areas covered: Low-dose aspirin related beneficial and adverse effects in cardiovascular system and gastrointestinal tract are reviewed. In addition, this manuscript summarizes current data on upper gastrointestinal damage prevention and adverse events with proton pump inhibition. Finally, we discuss the benefit/risk ratio of proton pump inhibitor use in patients at risk of gastrointestinal damage taking low-dose aspirin. Expert commentary: Nowadays, with the current available evidence, the combination of low-dose aspirin with proton pump inhibitor is the most effective therapy for cardiovascular prevention in patients at high gastrointestinal risk. However, further studies are needed to discover new effective strategies with less related adverse events.

The design features cells use to build their transmembrane proton gradient

NASA Astrophysics Data System (ADS)

Gunner, M. R.; Koder, Ronald

2017-02-01

Organisms store energy from food and sunlight as an electrochemical gradient across the membranes of mitochondria, chloroplasts and bacteria. The gradient arises from differences in the concentration of protons and ions on the negative (N) and positive (P) sides of these membranes. This perspective describes how the proton gradient is formed. One strategy is the movement of electrons but not protons across a membrane-embedded protein from a site of proton-releasing oxidative chemistry on the P-side of the protein to a site of proton-binding reductive chemistry on the N-side. Alternately, protons are directly pumped across membrane-embedded proteins, which have gated proton transfer pathways that are opened and closed, as well as internal sites where the proton affinity varies as the protein goes through the reaction cycle. The molecules that carry out these roles are complex, utilizing non-amino acid cofactors and earth-abundant metals. However, these are also potential sources of high-energy toxic byproducts. Understanding these reactions can open the door to their rational redesign, with possible beneficial effects as far-reaching as improving the global food supply, preventing neurodegenerative diseases, and better understanding the role of metabolism in aging.

The design features cells use to build their transmembrane proton gradient.

PubMed

Gunner, M R; Koder, Ronald

2017-02-07

Organisms store energy from food and sunlight as an electrochemical gradient across the membranes of mitochondria, chloroplasts and bacteria. The gradient arises from differences in the concentration of protons and ions on the negative (N) and positive (P) sides of these membranes. This perspective describes how the proton gradient is formed. One strategy is the movement of electrons but not protons across a membrane-embedded protein from a site of proton-releasing oxidative chemistry on the P-side of the protein to a site of proton-binding reductive chemistry on the N-side. Alternately, protons are directly pumped across membrane-embedded proteins, which have gated proton transfer pathways that are opened and closed, as well as internal sites where the proton affinity varies as the protein goes through the reaction cycle. The molecules that carry out these roles are complex, utilizing non-amino acid cofactors and earth-abundant metals. However, these are also potential sources of high-energy toxic byproducts. Understanding these reactions can open the door to their rational redesign, with possible beneficial effects as far-reaching as improving the global food supply, preventing neurodegenerative diseases, and better understanding the role of metabolism in aging.

Tracking Electron Uptake from a Cathode into Shewanella Cells: Implications for Energy Acquisition from Solid-Substrate Electron Donors

PubMed Central

Rajeev, Pournami; Jain, Abhiney; Pirbadian, Sahand; Okamoto, Akihiro; Gralnick, Jeffrey A.; El-Naggar, Mohamed Y.; Nealson, Kenneth H.

2018-01-01

ABSTRACT While typically investigated as a microorganism capable of extracellular electron transfer to minerals or anodes, Shewanella oneidensis MR-1 can also facilitate electron flow from a cathode to terminal electron acceptors, such as fumarate or oxygen, thereby providing a model system for a process that has significant environmental and technological implications. This work demonstrates that cathodic electrons enter the electron transport chain of S. oneidensis when oxygen is used as the terminal electron acceptor. The effect of electron transport chain inhibitors suggested that a proton gradient is generated during cathode oxidation, consistent with the higher cellular ATP levels measured in cathode-respiring cells than in controls. Cathode oxidation also correlated with an increase in the cellular redox (NADH/FMNH2) pool determined with a bioluminescence assay, a proton uncoupler, and a mutant of proton-pumping NADH oxidase complex I. This work suggested that the generation of NADH/FMNH2 under cathodic conditions was linked to reverse electron flow mediated by complex I. A decrease in cathodic electron uptake was observed in various mutant strains, including those lacking the extracellular electron transfer components necessary for anodic-current generation. While no cell growth was observed under these conditions, here we show that cathode oxidation is linked to cellular energy acquisition, resulting in a quantifiable reduction in the cellular decay rate. This work highlights a potential mechanism for cell survival and/or persistence on cathodes, which might extend to environments where growth and division are severely limited. PMID:29487241

Peptic ulcer disease - discharge

MedlinePlus

... will take two types of antibiotics and a proton pump inhibitor (PPI). These medicines may cause nausea, diarrhea, and ... NSAIDs, you will likely need to take a proton pump inhibitor for 8 weeks. Taking antacids as needed between ...

Preferential Heating of Oxygen 5+ Ions by Finite-Amplitude Oblique Alfven Waves

NASA Technical Reports Server (NTRS)

Maneva, Yana G.; Vinas, Adolfo; Araneda, Jamie; Poedts, Stefaan

2016-01-01

Minor ions in the fast solar wind are known to have higher temperatures and to flow faster than protons in the interplanetary space. In this study we combine previous research on parametric instability theory and 2.5D hybrid simulations to study the onset of preferential heating of Oxygen 5+ ions by large-scale finite-amplitude Alfven waves in the collisionless fast solar wind. We consider initially non-drifting isotropic multi-species plasma, consisting of isothermal massless fluid electrons, kinetic protons and kinetic Oxygen 5+ ions. The external energy source for the plasma heating and energization are oblique monochromatic Alfven-cyclotron waves. The waves have been created by rotating the direction of initial parallel pump, which is a solution of the multi-fluid plasma dispersion relation. We consider propagation angles theta less than or equal to 30 deg. The obliquely propagating Alfven pump waves lead to strong diffusion in the ion phase space, resulting in highly anisotropic heavy ion velocity distribution functions and proton beams. We discuss the application of the model to the problems of preferential heating of minor ions in the solar corona and the fast solar wind.

[Proton pump inhibitors in gastro-oesophageal reflux disease: what is the further step?].

PubMed

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.

Genome-Guided Analysis of Clostridium ultunense and Comparative Genomics Reveal Different Strategies for Acetate Oxidation and Energy Conservation in Syntrophic Acetate-Oxidising Bacteria

PubMed Central

Manzoor, Shahid; Schnürer, Anna; Müller, Bettina

2018-01-01

Syntrophic acetate oxidation operates close to the thermodynamic equilibrium and very little is known about the participating organisms and their metabolism. Clostridium ultunense is one of the most abundant syntrophic acetate-oxidising bacteria (SAOB) that are found in engineered biogas processes operating with high ammonia concentrations. It has been proven to oxidise acetate in cooperation with hydrogenotrophic methanogens. There is evidence that the Wood-Ljungdahl (WL) pathway plays an important role in acetate oxidation. In this study, we analysed the physiological and metabolic capacities of C. ultunense strain Esp and strain BST on genome scale and conducted a comparative study of all the known characterised SAOB, namely Syntrophaceticus schinkii, Thermacetogenium phaeum, Tepidanaerobacter acetatoxydans, and Pseudothermotoga lettingae. The results clearly indicated physiological robustness to be beneficial for anaerobic digestion environments and revealed unexpected metabolic diversity with respect to acetate oxidation and energy conservation systems. Unlike S. schinkii and Th. phaeum, C. ultunense clearly does not employ the oxidative WL pathway for acetate oxidation, as its genome (and that of P. lettingae) lack important key genes. In both of those species, a proton motive force is likely formed by chemical protons involving putative electron-bifurcating [Fe-Fe] hydrogenases rather than proton pumps. No genes encoding a respiratory Ech (energy-converting hydrogenase), as involved in energy conservation in Th. phaeum and S. schinkii, were identified in C. ultunense and P. lettingae. Moreover, two respiratory complexes sharing similarities to the proton-translocating ferredoxin:NAD+ oxidoreductase (Rnf) and the Na+ pumping NADH:quinone hydrogenase (NQR) were predicted. These might form a respiratory chain that is involved in the reduction of electron acceptors rather than protons. However, involvement of these complexes in acetate oxidation in C. ultunense and P. lettingae needs further study. This genome-based comparison provides a solid platform for future meta-proteomics and meta-transcriptomics studies and for metabolic engineering, control, and monitoring of SAOB. PMID:29690652

Genome-Guided Analysis of Clostridium ultunense and Comparative Genomics Reveal Different Strategies for Acetate Oxidation and Energy Conservation in Syntrophic Acetate-Oxidising Bacteria.

PubMed

Manzoor, Shahid; Schnürer, Anna; Bongcam-Rudloff, Erik; Müller, Bettina

2018-04-23

Syntrophic acetate oxidation operates close to the thermodynamic equilibrium and very little is known about the participating organisms and their metabolism. Clostridium ultunense is one of the most abundant syntrophic acetate-oxidising bacteria (SAOB) that are found in engineered biogas processes operating with high ammonia concentrations. It has been proven to oxidise acetate in cooperation with hydrogenotrophic methanogens. There is evidence that the Wood-Ljungdahl (WL) pathway plays an important role in acetate oxidation. In this study, we analysed the physiological and metabolic capacities of C. ultunense strain Esp and strain BS T on genome scale and conducted a comparative study of all the known characterised SAOB, namely Syntrophaceticus schinkii , Thermacetogenium phaeum , Tepidanaerobacter acetatoxydans , and Pseudothermotoga lettingae . The results clearly indicated physiological robustness to be beneficial for anaerobic digestion environments and revealed unexpected metabolic diversity with respect to acetate oxidation and energy conservation systems. Unlike S. schinkii and Th. phaeum , C. ultunense clearly does not employ the oxidative WL pathway for acetate oxidation, as its genome (and that of P. lettingae ) lack important key genes. In both of those species, a proton motive force is likely formed by chemical protons involving putative electron-bifurcating [Fe-Fe] hydrogenases rather than proton pumps. No genes encoding a respiratory Ech (energy-converting hydrogenase), as involved in energy conservation in Th. phaeum and S. schinkii, were identified in C. ultunense and P. lettingae . Moreover, two respiratory complexes sharing similarities to the proton-translocating ferredoxin:NAD⁺ oxidoreductase (Rnf) and the Na⁺ pumping NADH:quinone hydrogenase (NQR) were predicted. These might form a respiratory chain that is involved in the reduction of electron acceptors rather than protons. However, involvement of these complexes in acetate oxidation in C. ultunense and P. lettingae needs further study. This genome-based comparison provides a solid platform for future meta-proteomics and meta-transcriptomics studies and for metabolic engineering, control, and monitoring of SAOB.

Qualitative analysis of anatomopathological changes of gastric mucosa due to long term therapy with proton pump inhibitors: experimental studies x clinical studies.

PubMed

de Souza, Iure Kalinine Ferraz; da Silva, Alcino Lázaro; de Araújo, Alex; Santos, Fernanda Carolina Barbosa; Mendonça, Bernardo Pinto Coelho Keuffer

2013-01-01

For a few decades the long-term use of proton pump inhibitors has had wide application in the treatment of several gastrointestinal diseases. Since then, however, several studies have called attention to the possible development of anatomical and pathological changes of gastric mucosa, resulting from the long term use of this therapeutic modality. Recent experimental and clinical studies suggest that these changes have connection not only to the development of precancerous lesions, but also of gastric tumors. To present a qualitative analysis of anatomical and pathological changes of gastric mucosa resulting from the long-term use of proton pump inhibitors. The headings used were: proton pump inhibitors, precancerous lesions and gastric neoplasms for a non systematic review of the literature, based on Medline, Lillacs and Scielo. Twelve articles were selected from clinical (9) and experimental (3) studies, for qualitative analysis of the results. The gastric acid suppression by high doses of proton pump inhibitors induces hypergastrinemia and the consequent emergence of neuroendocrine tumors in animal models. Morphological changes most often found in these experimental studies were: enterochromaffin-like cell hyperplasia, neuroendocrine tumor, atrophy, metaplasia and adenocarcinoma. In the studies in humans, however, despite enterochromaffin-like cell hyperplasia, the other effects, neuroendocrine tumor and gastric atrophy, gastric metaplasia and or adenocarcinoma, were not identified. Although it is not possible to say that the long-term treatment with proton pump inhibitors induces the appearance or accelerates the development of gastric cancer in humans, several authors have suggested that prolonged administration of this drug could provoke the development of gastric cancer. Thus, the evidence demonstrated in the animal model as well as the large number of patients who do or will do a long-term treatment with proton pump inhibitors, justifies the maintenance of this important line of research.

EFFECT OF CYP2C19 GENETIC POLYMORPHISMS ON THE EFFICACY OF PROTON PUMP INHIBITOR-BASED TRIPLE ERADICATION THERAPY IN SLAVIC PATIENTS WITH PEPTIC ULCERS: A META-ANALYSIS.

PubMed

Denisenko, N P; Sychev, D A; Sizova, Zh M; Rozhkov, A V; Kondrashov, A V

Several meta-analyzes reported the effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple therapy for Helicobacter pylori eradication. Most of the studies which were included in these meta-analyzes were held on Asian population. Thus, there is lack of information about the effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple eradication therapy in Slavic patients with peptic ulcers. The aim of the study - to determine whether CYP2C19 affect the efficacy of proton pump inhibitor-based triple eradica- tion therapy in Slavic patients with peptic ulcers. Data search was performed using Russian index of scientific citation database, Google Scholar and MEDLINE PubMed. Statistics was held in Review Manager v 5.3. The odds ratio (OR) and 95% confidence interval (95% Cl) for eradication of H.pylori was estimated in a fixed-effect model when no heterogeneity across the studies was indicated. Four articles published between 2008 and 2015 were included in meta-analysis (three Russian studies, one Polish study). Eradication rates were significantly lower in CYP2C19 extensive metabolizers of proton pump inhibitors than in a combined group of intermediate and poor metabolizers (OR = 1,90, CI-95% 1,08-3,34, p = 0,03; heterogeneity: 12= 0%, p = 0,74). We also found that proton pump inhibitor-based triple eradication therapy achieved higher rates in poor metabolizers than in a combined group of intermediate and extensive metabolizers of CYP2C19 (OR= 5,48 CI-95% 1,51-19,93, p = 0,01; heterogeneity: F= 0%, p = 0,66). The impact of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple eradication therapy in Slavic patients appears significant.

46 CFR 56.50-55 - Bilge pumps.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Each self-propelled vessel must be provided with a power-driven pump or pumps connected to the bilge... power-driven pump is required. (See Part 171 of this chapter for determination of criterion numeral.) 5... available, or where a suitable water supply is available from a power-driven pump of adequate pressure and...

Effects of membrane curvature and pH on proton pumping activity of single cytochrome bo3 enzymes.

PubMed

Li, Mengqiu; Khan, Sanobar; Rong, Honglin; Tuma, Roman; Hatzakis, Nikos S; Jeuken, Lars J C

2017-09-01

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 bo 3 , 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 bo 3 was found to decrease with increased curvature of the membrane. Furthermore, proton uptake at the N-side (proton entrance) was insensitive to pH between pH6.4-8.4, while proton release at the P-side had an optimum pH of ~7.4, suggesting that the pH optimum is related to proton release from the proton exit site. Our previous single-enzyme experiments identified rare, long-lived conformation states of cytochrome bo 3 where protons leak back under turn-over conditions. Here, we analyzed and found that ~23% of cytochrome bo 3 proteoliposomes show ΔpH half-lives below 50s after stopping turnover, while only ~5% of the proteoliposomes containing a non-pumping mutant, E286C cytochrome bo 3 exhibit such fast decays. These single-enzyme results confirm our model in which HCO exhibit heterogeneous pumping rates and can adopt rare leak states in which protons are able to rapidly flow back. Copyright © 2017 Elsevier B.V. All rights reserved.

Carbon Nanotubes as an Ultrafast Emitter with a Narrow Energy Spread at Optical Frequency.

PubMed

Li, Chi; Zhou, Xu; Zhai, Feng; Li, Zhenjun; Yao, Fengrui; Qiao, Ruixi; Chen, Ke; Cole, Matthew Thomas; Yu, Dapeng; Sun, Zhipei; Liu, Kaihui; Dai, Qing

2017-08-01

Ultrafast electron pulses, combined with laser-pump and electron-probe technologies, allow ultrafast dynamics to be characterized in materials. However, the pursuit of simultaneous ultimate spatial and temporal resolution of microscopy and spectroscopy is largely subdued by the low monochromaticity of the electron pulses and their poor phase synchronization to the optical excitation pulses. Field-driven photoemission from metal tips provides high light-phase synchronization, but suffers large electron energy spreads (3-100 eV) as driven by a long wavelength laser (>800 nm). Here, ultrafast electron emission from carbon nanotubes (≈1 nm radius) excited by a 410 nm femtosecond laser is realized in the field-driven regime. In addition, the emitted electrons have great monochromaticity with energy spread as low as 0.25 eV. This great performance benefits from the extraordinarily high field enhancement and great stability of carbon nanotubes, superior to metal tips. The new nanotube-based ultrafast electron source opens exciting prospects for extending current characterization to sub-femtosecond temporal resolution as well as sub-nanometer spatial resolution. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cooperative inter- and intra-layer lattice dynamics of photoexcited multi-walled carbon nanotubes studied by ultrafast electron diffraction.

PubMed

Sun, Shuaishuai; Li, Zhongwen; Li, Zi-An; Xiao, Ruijuan; Zhang, Ming; Tian, Huanfang; Yang, Huaixin; Li, Jianqi

2018-04-26

Optical tuning and probing ultrafast structural response of nanomaterials driven by electronic excitation constitute a challenging but promising approach for understanding microscopic mechanisms and applications in microelectromechanical systems and optoelectrical devices. Here we use pulsed electron diffraction in a transmission electron microscope to investigate laser-induced tubular lattice dynamics of multi-walled carbon nanotubes (MWCNTs) with varying laser fluence and initial specimen temperature. Our photoexcitation experiments demonstrate cooperative and inverse collective atomic motions in intralayer and interlayer directions, whose strengths and rates depend on pump fluence. The electron-driven and thermally driven structural responses with opposite amplitudes cause a crossover between intralayer and interlayer directions. Our ab initio calculations support these findings and reveal that electrons excited from π to π* orbitals in a carbon tube weaken the intralayer bonds while strengthening the interlayer bonds along the radial direction. Moreover, by probing the structural dynamics of MWCNTs at initial temperatures of 300 and 100 K, we uncover the concomitance of thermal and nonthermal dynamical processes and their mutual influence in MWCNTs. Our results illustrate the nature of electron-driven nonthermal process and electron-phonon thermalization in the MWCNTs, and bear implications for the intricate energy conversion and transfer in materials at the nanoscale.

Conjecture Regarding Posttranslational Modifications to the Arabidopsis Type I Proton-Pumping Pyrophosphatase (AVP1)

PubMed Central

Pizzio, Gaston A.; Hirschi, Kendal D.; Gaxiola, Roberto A.

2017-01-01

Agbiotechnology uses genetic engineering to improve the output and value of crops. Altering the expression of the plant Type I Proton-pumping Pyrophosphatase (H+-PPase) has already proven to be a useful tool to enhance crop productivity. Despite the effective use of this gene in translational research, information regarding the intracellular localization and functional plasticity of the pump remain largely enigmatic. Using computer modeling several putative phosphorylation, ubiquitination and sumoylation target sites were identified that may regulate Arabidopsis H+-PPase (AVP1- Arabidopsis Vacuolar Proton-pump 1) subcellular trafficking and activity. These putative regulatory sites will direct future research that specifically addresses the partitioning and transport characteristics of this pump. We posit that fine-tuning H+-PPases activity and cellular distribution will facilitate rationale strategies for further genetic improvements in crop productivity. PMID:28955362

Confinement time of electron plasma approaching magnetic pumping transport limit in small aspect ratio C-shaped torus

NASA Astrophysics Data System (ADS)

Lachhvani, Lavkesh; Pahari, Sambaran; Goswami, Rajiv; Bajpai, Manu; Yeole, Yogesh; Chattopadhyay, P. K.

2016-06-01

A long confinement time of electron plasma, approaching magnetic pumping transport limit, has been observed in SMARTEX-C (a small aspect ratio partial torus with R o / a ˜ 1.59 ). Investigations of the growth rate reveal that they are governed by instabilities like resistive wall destabilization, ion driven instabilities, and electron-neutral collisions. Successful confinement of electron plasmas exceeding > 1 × 10 5 poloidal E → × B → rotations lasting for nearly 2.1 ± 0.1 s is achieved by suppressing these instabilities. The confinement time has been estimated in two ways: (a) from the frequency scaling of the linear diocotron mode launched from sections of the wall that are also used as capacitive probes and (b) by dumping the plasma onto a charge collector at different hold times.

Time-resolved measurements with streaked diffraction patterns from electrons generated in laser plasma wakefield

NASA Astrophysics Data System (ADS)

He, Zhaohan; Nees, John; Hou, Bixue; Krushelnick, Karl; Thomas, Alec; Beaurepaire, Benoît; Malka, Victor; Faure, Jérôme

2013-10-01

Femtosecond bunches of electrons with relativistic to ultra-relativistic energies can be robustly produced in laser plasma wakefield accelerators (LWFA). Scaling the electron energy down to sub-relativistic and MeV level using a millijoule laser system will make such electron source a promising candidate for ultrafast electron diffraction (UED) applications due to the intrinsic short bunch duration and perfect synchronization with the optical pump. Recent results of electron diffraction from a single crystal gold foil, using LWFA electrons driven by 8-mJ, 35-fs laser pulses at 500 Hz, will be presented. The accelerated electrons were collimated with a solenoid magnetic lens. By applying a small-angle tilt to the magnetic lens, the diffraction pattern can be streaked such that the temporal evolution is separated spatially on the detector screen after propagation. The observable time window and achievable temporal resolution are studied in pump-probe measurements of photo-induced heating on the gold foil.

A cryo-cooled high-energy DPSSL system delivering ns-pulses at 10 J and 10 Hz

NASA Astrophysics Data System (ADS)

Ertel, Klaus; Banerjee, Saumyabrata; Butcher, Thomas J.; De Vido, Mariastefania; Mason, Paul D.; Phillips, P. J.; Richards, David; Shaikh, Waseem; Smith, Jodie M.; Greenhalgh, R. Justin S.; Hernandez-Gomez, Cristina; Collier, John L.

2015-02-01

Lasers generating multi-J to kJ ns-pulses are required for many types of laser-plasma interactions. Such lasers are either used directly for compressing matter to extreme densities or they serve as pump lasers for short-pulses laser chains based on large-aperture Ti:sapphire or parametric amplifiers. The thus generated high-energy fs-pulses are most useful for laser driven secondary sources of particles (electrons, protons) or photons (from THz to gamma). While proof-of-principle experiments have been carried out with flashlamp-pumped glass lasers, lasers with much higher efficiency and repetition rate are required to make this applications practically viable. We have developed a scalable new laser concept called DiPOLE (diode pumped optical laser for experiments) based on a gas-cooled ceramic Yb:YAG multi-slab architecture operating at cryogenic temperatures. While the viability of this concept has been shown earlier [1], we have now reached our target performance of 10 J pulse energy at 10 Hz repetition rate at an optical-to-optical efficiency of 21%. To the best of our knowledge, these are record values for average power and efficiency for lasers of this type. We have also upgraded the system by adding a fibre-based front-end system with arbitrary pulse shaping capability and by installing an image-relayed multipass system enabling up to eight passes of the main amplifier. We have then used this system to demonstrate frequency doubling with 65 % conversion efficiency and a long-term shot-to-shot stability of 0.5% rms over a total of nearly 2 million shots, achieved in runs extending over 4 to 6 hours.

Multilayered Polyelectrolyte Microcapsules: Interaction with the Enzyme Cytochrome C Oxidase

PubMed Central

Pastorino, Laura; Dellacasa, Elena; Noor, Mohamed R.; Soulimane, Tewfik; Bianchini, Paolo; D'Autilia, Francesca; Antipov, Alexei; Diaspro, Alberto; Tofail, Syed A. M.; Ruggiero, Carmelina

2014-01-01

Cell-sized polyelectrolyte capsules functionalized with a redox-driven proton pump protein were assembled for the first time. The interaction of polyelectrolyte microcapsules, fabricated by electrostatic layer-by-layer assembly, with cytochrome c oxidase molecules was investigated. We found that the cytochrome c oxidase retained its functionality, that the functionalized microcapsules interacting with cytochrome c oxidase were permeable and that the permeability characteristics of the microcapsule shell depend on the shell components. This work provides a significant input towards the fabrication of an integrated device made of biological components and based on specific biomolecular functions and properties. PMID:25372607

Reduction of Flavodoxin by Electron Bifurcation and Sodium Ion-dependent Reoxidation by NAD+ Catalyzed by Ferredoxin-NAD+ Reductase (Rnf)*

PubMed Central

Chowdhury, Nilanjan Pal; Klomann, Katharina; Seubert, Andreas; Buckel, Wolfgang

2016-01-01

Electron-transferring flavoprotein (Etf) and butyryl-CoA dehydrogenase (Bcd) from Acidaminococcus fermentans catalyze the endergonic reduction of ferredoxin by NADH, which is also driven by the concomitant reduction of crotonyl-CoA by NADH, a process called electron bifurcation. Here we show that recombinant flavodoxin from A. fermentans produced in Escherichia coli can replace ferredoxin with almost equal efficiency. After complete reduction of the yellow quinone to the blue semiquinone, a second 1.4 times faster electron transfer affords the colorless hydroquinone. Mediated by a hydrogenase, protons reoxidize the fully reduced flavodoxin or ferredoxin to the semi-reduced species. In this hydrogen-generating system, both electron carriers act catalytically with apparent Km = 0.26 μm ferredoxin or 0.42 μm flavodoxin. Membrane preparations of A. fermentans contain a highly active ferredoxin/flavodoxin-NAD+ reductase (Rnf) that catalyzes the irreversible reduction of flavodoxin by NADH to the blue semiquinone. Using flavodoxin hydroquinone or reduced ferredoxin obtained by electron bifurcation, Rnf can be measured in the forward direction, whereby one NADH is recycled, resulting in the simple equation: crotonyl-CoA + NADH + H+ = butyryl-CoA + NAD+ with Km = 1.4 μm ferredoxin or 2.0 μm flavodoxin. This reaction requires Na+ (Km = 0.12 mm) or Li+ (Km = 0.25 mm) for activity, indicating that Rnf acts as a Na+ pump. The redox potential of the quinone/semiquinone couple of flavodoxin (Fld) is much higher than that of the semiquinone/hydroquinone couple. With free riboflavin, the opposite is the case. Based on this behavior, we refine our previous mechanism of electron bifurcation. PMID:27048649

Laser-induced electron dynamics including photoionization: A heuristic model within time-dependent configuration interaction theory.

PubMed

Klinkusch, Stefan; Saalfrank, Peter; Klamroth, Tillmann

2009-09-21

We report simulations of laser-pulse driven many-electron dynamics by means of a simple, heuristic extension of the time-dependent configuration interaction singles (TD-CIS) approach. The extension allows for the treatment of ionizing states as nonstationary states with a finite, energy-dependent lifetime to account for above-threshold ionization losses in laser-driven many-electron dynamics. The extended TD-CIS method is applied to the following specific examples: (i) state-to-state transitions in the LiCN molecule which correspond to intramolecular charge transfer, (ii) creation of electronic wave packets in LiCN including wave packet analysis by pump-probe spectroscopy, and, finally, (iii) the effect of ionization on the dynamic polarizability of H(2) when calculated nonperturbatively by TD-CIS.

Proton pump inhibitor-induced tumour cell death by inhibition of a detoxification mechanism.

PubMed

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.

Are higher doses of proton pump inhibitors better in acute peptic bleeding?

PubMed

Villalón, Alejandro; Olmos, Roberto; Rada, Gabriel

2016-06-24

Although there is broad consensus about the benefits of proton pump inhibitors in acute upper peptic bleeding, there is still controversy over their optimal dosing. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 27 randomized trials addressing this question. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded high-dose proton pump inhibitors probably result in little or no difference in re-bleeding rate or mortality. The risk/benefit and cost/benefit balance probably favor use of low-doses.

Persistent reflux symptoms cause anxiety, depression, and mental health and sleep disorders in gastroesophageal reflux disease patients

PubMed Central

Kimura, Yoshihide; Kamiya, Takeshi; Senoo, Kyouji; Tsuchida, Kenji; Hirano, Atsuyuki; Kojima, Hisayo; Yamashita, Hiroaki; Yamakawa, Yoshihiro; Nishigaki, Nobuhiro; Ozeki, Tomonori; Endo, Masatsugu; Nakanishi, Kazuhisa; Sando, Motoki; Inagaki, Yusuke; Shikano, Michiko; Mizoshita, Tsutomu; Kubota, Eiji; Tanida, Satoshi; Kataoka, Hiromi; Katsumi, Kohei; Joh, Takashi

2016-01-01

Some patients with gastroesophageal reflux disease experience persistent reflux symptoms despite proton pump inhibitor therapy. These symptoms reduce their health-related quality of life. Our aims were to evaluate the relationship between proton pump inhibitor efficacy and health-related quality of life and to evaluate predictive factors affecting treatment response in Japanese patients. Using the gastroesophageal reflux disease questionnaire, 145 gastroesophageal reflux disease patients undergoing proton pump inhibitor therapy were evaluated and classified as responders or partial-responders. Their health-related quality of life was then evaluated using the 8-item Short Form Health Survey, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale questionnaires. Sixty-nine patients (47.6%) were partial responders. These patients had significantly lower scores than responders in 5/8 subscales and in the mental health component summary of the 8-item Short Form Health Survey. Partial responders had significantly higher Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale scores, including anxiety and depression scores, than those of responders. Non-erosive reflux disease and double proton pump inhibitor doses were predictive factors of partial responders. Persistent reflux symptoms, despite proton pump inhibitor therapy, caused mental health disorders, sleep disorders, and psychological distress in Japanese gastroesophageal reflux disease patients. PMID:27499583

[Pharmacogenic osteoporosis beyond cortisone. Proton pump inhibitors, glitazones and diuretics].

PubMed

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.

Persistent reflux symptoms cause anxiety, depression, and mental health and sleep disorders in gastroesophageal reflux disease patients.

PubMed

Kimura, Yoshihide; Kamiya, Takeshi; Senoo, Kyouji; Tsuchida, Kenji; Hirano, Atsuyuki; Kojima, Hisayo; Yamashita, Hiroaki; Yamakawa, Yoshihiro; Nishigaki, Nobuhiro; Ozeki, Tomonori; Endo, Masatsugu; Nakanishi, Kazuhisa; Sando, Motoki; Inagaki, Yusuke; Shikano, Michiko; Mizoshita, Tsutomu; Kubota, Eiji; Tanida, Satoshi; Kataoka, Hiromi; Katsumi, Kohei; Joh, Takashi

2016-07-01

Some patients with gastroesophageal reflux disease experience persistent reflux symptoms despite proton pump inhibitor therapy. These symptoms reduce their health-related quality of life. Our aims were to evaluate the relationship between proton pump inhibitor efficacy and health-related quality of life and to evaluate predictive factors affecting treatment response in Japanese patients. Using the gastroesophageal reflux disease questionnaire, 145 gastroesophageal reflux disease patients undergoing proton pump inhibitor therapy were evaluated and classified as responders or partial-responders. Their health-related quality of life was then evaluated using the 8-item Short Form Health Survey, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale questionnaires. Sixty-nine patients (47.6%) were partial responders. These patients had significantly lower scores than responders in 5/8 subscales and in the mental health component summary of the 8-item Short Form Health Survey. Partial responders had significantly higher Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale scores, including anxiety and depression scores, than those of responders. Non-erosive reflux disease and double proton pump inhibitor doses were predictive factors of partial responders. Persistent reflux symptoms, despite proton pump inhibitor therapy, caused mental health disorders, sleep disorders, and psychological distress in Japanese gastroesophageal reflux disease patients.

What is heartburn worth? A cost-utility analysis of management strategies.

PubMed

Heudebert, G R; Centor, R M; Klapow, J C; Marks, R; Johnson, L; Wilcox, C M

2000-03-01

To determine the best treatment strategy for the management of patients presenting with symptoms consistent with uncomplicated heartburn. We performed a cost-utility analysis of 4 alternatives: empirical proton pump inhibitor, empirical histamine2-receptor antagonist, and diagnostic strategies consisting of either esophagogastroduodenoscopy (EGD) or an upper gastrointestinal series before treatment. The time horizon of the model was 1 year. The base case analysis assumed a cohort of otherwise healthy 45-year-old individuals in a primary care practice. Empirical treatment with a proton pump inhibitor was projected to provide the greatest quality-adjusted survival for the cohort. Empirical treatment with a histamine2 receptor antagonist was projected to be the least costly of the alternatives. The marginal cost-effectiveness of using a proton pump inhibitor over a histamine2-receptor antagonist was approximately $10,400 per quality-adjusted life year (QALY) gained in the base case analysis and was less than $50,000 per QALY as long as the utility for heartburn was less than 0.95. Both diagnostic strategies were dominated by proton pump inhibitor alternative. Empirical treatment seems to be the optimal initial management strategy for patients with heartburn, but the choice between a proton pump inhibitor or histamine2-receptor antagonist depends on the impact of heartburn on quality of life.

What Is Heartburn Worth?

PubMed Central

Heudebert, Gustavo R; Centor, Robert M; Klapow, Joshua C; Marks, Robert; Johnson, Lawrence; Wilcox, C Mel

2000-01-01

OBJECTIVE T o determine the best treatment strategy for the management of patients presenting with symptoms consistent with uncomplicated heartburn. METHODS We performed a cost-utility analysis of 4 alternatives: empirical proton pump inhibitor, empirical histamine2-receptor antagonist, and diagnostic strategies consisting of either esophagogastroduodenoscopy (EGD) or an upper gastrointestinal series before treatment. The time horizon of the model was 1 year. The base case analysis assumed a cohort of otherwise healthy 45-year-old individuals in a primary care practice. MAIN RESULTS Empirical treatment with a proton pump inhibitor was projected to provide the greatest quality-adjusted survival for the cohort. Empirical treatment with a histamine2receptor antagonist was projected to be the least costly of the alternatives. The marginal cost-effectiveness of using a proton pump inhibitor over a histamine2-receptor antagonist was approximately $10,400 per quality-adjusted life year (QALY) gained in the base case analysis and was less than $50,000 per QALY as long as the utility for heartburn was less than 0.95. Both diagnostic strategies were dominated by proton pump inhibitor alternative. CONCLUSIONS Empirical treatment seems to be the optimal initial management strategy for patients with heartburn, but the choice between a proton pump inhibitor or histamine2-receptor antagonist depends on the impact of heartburn on quality of life. PMID:10718898

The role of geochemistry and energetics in the evolution of modern respiratory complexes from a proton-reducing ancestor.

PubMed

Schut, Gerrit J; Zadvornyy, Oleg; Wu, Chang-Hao; Peters, John W; Boyd, Eric S; Adams, Michael W W

2016-07-01

Complex I or NADH quinone oxidoreductase (NUO) is an integral component of modern day respiratory chains and has a close evolutionary relationship with energy-conserving [NiFe]-hydrogenases of anaerobic microorganisms. Specifically, in all of biology, the quinone-binding subunit of Complex I, NuoD, is most closely related to the proton-reducing, H2-evolving [NiFe]-containing catalytic subunit, MbhL, of membrane-bound hydrogenase (MBH), to the methanophenzine-reducing subunit of a methanogenic respiratory complex (FPO) and to the catalytic subunit of an archaeal respiratory complex (MBX) involved in reducing elemental sulfur (S°). These complexes also pump ions and have at least 10 homologous subunits in common. As electron donors, MBH and MBX use ferredoxin (Fd), FPO uses either Fd or cofactor F420, and NUO uses either Fd or NADH. In this review, we examine the evolutionary trajectory of these oxidoreductases from a proton-reducing ancestral respiratory complex (ARC). We hypothesize that the diversification of ARC to MBH, MBX, FPO and eventually NUO was driven by the larger energy yields associated with coupling Fd oxidation to the reduction of oxidants with increasing electrochemical potential, including protons, S° and membrane soluble organic compounds such as phenazines and quinone derivatives. Importantly, throughout Earth's history, the availability of these oxidants increased as the redox state of the atmosphere and oceans became progressively more oxidized as a result of the origin and ecological expansion of oxygenic photosynthesis. ARC-derived complexes are therefore remarkably stable respiratory systems with little diversity in core structure but whose general function appears to have co-evolved with the redox state of the biosphere. This article is part of a Special Issue entitled Respiratory Complex I, edited by Volker Zickermann and Ulrich Brandt. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of Electron-Driven Proton-Transfer Processes in the Ultrafast Deactivation of Photoexcited Anionic 8-oxoGuanine-Adenine and 8-oxoGuanine-Cytosine Base Pairs.

PubMed

Wu, Xiuxiu; Karsili, Tolga N V; Domcke, Wolfgang

2017-01-14

It has been reported that 8-oxo-7,8-dihydro-guanosine (8-oxo-G), which is the main product of oxidative damage of DNA, can repair cyclobutane pyrimidine dimer (CPD) lesions when incorporated into DNA or RNA strands in proximity to such lesions. It has therefore been suggested that the 8-oxo-G nucleoside may have been a primordial precursor of present-day flavins in DNA or RNA repair. Because the electron transfer leading to the splitting of a thymine-thymine pair in a CPD lesion occurs in the photoexcited state, a reasonably long excited-state lifetime of 8-oxo-G is required. The neutral (protonated) form of 8-oxo-G exhibits a very short (sub-picosecond) intrinsic excited-state lifetime which is unfavorable for repair. It has therefore been argued that the anionic (deprotonated) form of 8-oxo-G, which exhibits a much longer excited-state lifetime, is more likely to be a suitable cofactor for DNA repair. Herein, we have investigated the exited-state quenching mechanisms in the hydrogen-bonded complexes of deprotonated 8-oxo-G - with adenine (A) and cytosine (C) using ab initio wave-function-based electronic-structure calculations. The calculated reaction paths and potential-energy profiles reveal the existence of barrierless electron-driven inter-base proton-transfer reactions which lead to low-lying S₁/S₀ conical intersections. The latter can promote ultrafast excited-state deactivation of the anionic base pairs. While the isolated deprotonated 8-oxo-G - nucleoside may have been an efficient primordial repair cofactor, the excited states of the 8-oxo-G - -A and 8-oxo-G - -C base pairs are likely too short-lived to be efficient electron-transfer repair agents.

Inhibition of electron transfer and uncoupling effects by emodin and emodinanthrone in Escherichia coli

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ubbink-Kok, T.; Anderson, J.A.; Konings, W.N.

1986-07-01

The anthraquinones emodin (1,3,delta-trihydroxy-6-methylanthraquinone) and emodinanthrone (1,3,8-trihydroxy-6-methylanthrone) inhibited respiration-driven solute transport at micromolar concentrations in membrane vesicles of Escherichia coli. This inhibition was enhanced by Ca ions. The inhibitory action on solute transport is caused by inhibition of electron flow in the respiratory chain, most likely at the level between ubiquinone and cytochrome b, and by dissipation of the proton motive force. The uncoupling action was confirmed by studies on the proton motive force in beef heart cytochrome oxidase proteoliposomes. These two effects on energy transduction in cytoplasmic membranes explain the antibiotic properties of emodin and emodinanthrone.

Inhibition of electron transfer and uncoupling effects by emodin and emodinanthrone in Escherichia coli.

PubMed

Ubbink-Kok, T; Anderson, J A; Konings, W N

1986-07-01

The anthraquinones emodin (1,3,delta-trihydroxy-6-methylanthraquinone) and emodinanthrone (1,3,8-trihydroxy-6-methylanthrone) inhibited respiration-driven solute transport at micromolar concentrations in membrane vesicles of Escherichia coli. This inhibition was enhanced by Ca ions. The inhibitory action on solute transport is caused by inhibition of electron flow in the respiratory chain, most likely at the level between ubiquinone and cytochrome b, and by dissipation of the proton motive force. The uncoupling action was confirmed by studies on the proton motive force in beef heart cytochrome oxidase proteoliposomes. These two effects on energy transduction in cytoplasmic membranes explain the antibiotic properties of emodin and emodinanthrone.

Nonthermal Radiation Processes in Interplanetary Plasmas

NASA Astrophysics Data System (ADS)

Chian, A. C. L.

1990-11-01

RESUMEN. En la interacci6n de haces de electrones energeticos con plasmas interplanetarios, se excitan ondas intensas de Langmuir debido a inestabilidad del haz de plasma. Las ondas Langmuir a su vez interaccio nan con fluctuaciones de densidad de baja frecuencia para producir radiaciones. Si la longitud de las ondas de Langmujr exceden las condicio nes del umbral, se puede efectuar la conversi5n de modo no lineal a on- das electromagneticas a traves de inestabilidades parametricas. As se puede excitar en un plasma inestabilidades parametricas electromagneticas impulsadas por ondas intensas de Langmuir: (1) inestabilidades de decaimiento/fusi5n electromagnetica impulsadas por una bomba de Lang- muir que viaja; (2) inestabilidades dobles electromagneticas de decai- miento/fusi5n impulsadas por dos bombas de Langrnuir directamente opues- tas; y (3) inestabilidades de dos corrientes oscilatorias electromagne- ticas impulsadas por dos bombas de Langmuir de corrientes contrarias. Se concluye que las inestabilidades parametricas electromagneticas in- ducidas por las ondas de Langmuir son las fuentes posibles de radiacio- nes no termicas en plasmas interplanetarios. ABSTRACT: Nonthermal radio emissions near the local electron plasma frequency have been detected in various regions of interplanetary plasmas: solar wind, upstream of planetary bow shock, and heliopause. Energetic electron beams accelerated by solar flares, planetary bow shocks, and the terminal shock of heliosphere provide the energy source for these radio emissions. Thus, it is expected that similar nonthermal radiation processes may be responsible for the generation of these radio emissions. As energetic electron beams interact with interplanetary plasmas, intense Langmuir waves are excited due to a beam-plasma instability. The Langmuir waves then interact with low-frequency density fluctuations to produce radiations near the local electron plasma frequency. If Langmuir waves are of sufficiently large amplitude to exceed the thresfiold conditions, nonlinear mode conversion electromagnetic waves can be effected through parametric instabilities. A number of electromagnetic parametric instabilities driven by intense Langmuir waves can be excited in a plasma: (1) electromagnetic decay/fusion instabilities driven by a traveling Langmuir pump; (2) double electromagnetic decay/fusion instabilities driven by two oppositely directed Langmuir pumps; and (3) electromagnetic oscillating two-stream instabilities driven by two counterstreaming Langmuir pumps. It is concluded that the electromagnetic parametric instabilities induced by Langmuir waves are likely sources of nonthermal radiations in interplanetary plasmas. Keq ( : INTERPLANETARY MEDIUM - PLASMAS

PHYSIOLOGY OF ION TRANSPORT ACROSS THE TONOPLAST OF HIGHER PLANTS.

PubMed

Barkla, Bronwyn J.; Pantoja, Omar

1996-06-01

The vacuole of plant cells plays an important role in the homeostasis of the cell. It is involved in the regulation of cytoplasmic pH, sequestration of toxic ions and xenobiotics, regulation of cell turgor, storage of amino acids, sugars and CO2 in the form of malate, and possibly as a source for elevating cytoplasmic calcium. All these activities are driven by two primary active transport mechanisms present in the vacuolar membrane (tonoplast). These two mechanisms employ high-energy metabolites to pump protons into the vacuole, establishing a proton electrochemical potential that mediates the transport of a diverse range of solutes. Within the past few years, great advances at the molecular and functional levels have been made on the characterization and identification of these mechanisms. The aim of this review is to summarize these studies in the context of the physiology of the plant cell.

A population-based study of the drug interaction between proton pump inhibitors and clopidogrel

PubMed Central

Juurlink, David N.; Gomes, Tara; Ko, Dennis T.; Szmitko, Paul E.; Austin, Peter C.; Tu, Jack V.; Henry, David A.; Kopp, Alex; Mamdani, Muhammad M.

2009-01-01

Background Most proton pump inhibitors inhibit the bioactivation of clopidogrel to its active metabolite. The clinical significance of this drug interaction is unknown. Methods We conducted a population-based nested case–control study among patients aged 66 years or older who commenced clopidogrel between Apr. 1, 2002, and Dec. 31, 2007, following hospital discharge after treatment of acute myocardial infarction. The cases in our study were those readmitted with acute myocardial infarction within 90 days after discharge. We performed a secondary analysis considering events within 1 year. Event-free controls (at a ratio of 3:1) were matched to cases on age, percutaneous coronary intervention and a validated risk score. We categorized exposure to proton pump inhibitors before the index date as current (within 30 days), previous (31–90 days) or remote (91–180 days). Results Among 13 636 patients prescribed clopidogrel following acute myocardial infarction, we identified 734 cases readmitted with myocardial infarction and 2057 controls. After extensive multivariable adjustment, current use of proton pump inhibitors was associated with an increased risk of reinfarction (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.03–1.57). We found no association with more distant exposure to proton pump inhibitors or in multiple sensitivity analyses. In a stratified analysis, pantoprazole, which does not inhibit cytochrome P450 2C19, had no association with readmission for myocardial infarction (adjusted OR 1.02, 95% CI 0.70–1.47). Interpretation Among patients receiving clopidogrel following acute myocardial infarction, concomitant therapy with proton pump inhibitors other than pantoprazole was associated with a loss of the beneficial effects of clopidogrel and an increased risk of reinfarction. PMID:19176635

The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease.

PubMed

Savarino, Edoardo; Marabotto, Elisa; Zentilin, Patrizia; Frazzoni, Marzio; Sammito, Giorgio; Bonfanti, Daria; Sconfienza, Luca; Assandri, Lorenzo; Gemignani, Lorenzo; Malesci, Alberto; Savarino, Vincenzo

2011-07-01

Functional heartburn is defined by Rome III criteria as an endoscopy-negative condition with normal oesophageal acid exposure time, negative symptom association to acid reflux and unsatisfactory response to proton pump inhibitors. These criteria underestimated the role of non-acid reflux. To assess the contribution of impedance-pH with symptom association probability (SAP) analysis in identifying endoscopy-negative patients with reflux disease and separating them from functional heartburn. Consecutive endoscopy-negative patients treated with proton pump inhibitors (n=219) undergoing impedance-pH monitoring off-therapy were analysed. Distal acid exposure time, reflux episodes, SAP and symptomatic response to proton pump inhibitors were measured. Based on impedance-pH/SAP, 67 (31%) patients were pH+/SAP+, 6 (2%) pH+/SAP-, 83 (38%) hypersensitive oesophagus and 63 (29%) functional heartburn. According to pH-metry alone/response to proton pump inhibitors, 62 (28%) were pH+/SAP+, 11 (5%) pH+/SAP-, 61 (28%) hypersensitive oesophagus and 85 (39%) functional heartburn. In the normal-acid exposure population the contribution of impedance-pH/SAP compared to pH-metry alone/response to proton pump inhibitors in identifying patients with reflux disease and functional heartburn resulted to be 10%. In patients with abnormal-acid exposure, the contribution of impedance-pH/SAP increased by 3%. Comparing impedance-pH testing with pH-metry alone plus the response to proton pump inhibitor therapy demonstrated that the latter ones cause underestimation of reflux disease patients and overestimation of functional heartburn patients. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Electrostatic waves driven by electron beam in lunar wake plasma

NASA Astrophysics Data System (ADS)

Sreeraj, T.; Singh, S. V.; Lakhina, G. S.

2018-05-01

A linear analysis of electrostatic waves propagating parallel to the ambient field in a four component homogeneous, collisionless, magnetised plasma comprising fluid protons, fluid He++, electron beam, and suprathermal electrons following kappa distribution is presented. In the absence of electron beam streaming, numerical analysis of the dispersion relation shows six modes: two electron acoustic modes (modes 1 and 6), two fast ion acoustic modes (modes 2 and 5), and two slow ion acoustic modes (modes 3 and 4). The modes 1, 2 and 3 and modes 4, 5, and 6 have positive and negative phase speeds, respectively. With an increase in electron beam speed, the mode 6 gets affected the most and the phase speed turns positive from negative. The mode 6 thus starts to merge with modes 2 and 3 and generates the electron beam driven fast and slow ion acoustic waves unstable with a finite growth. The electron beam driven slow ion-acoustic waves occur at lower wavenumbers, whereas fast ion-acoustic waves occur at a large value of wavenumbers. The effect of various other parameters has also been studied. We have applied this analysis to the electrostatic waves observed in lunar wake during the first flyby of the ARTEMIS mission. The analysis shows that the low (high) frequency waves observed in the lunar wake could be the electron beam driven slow (fast) ion-acoustic modes.

Proton deflectometry of laser-driven relativistic electron jet from thin foil target

NASA Astrophysics Data System (ADS)

Huang, Chengkun; Palaniyappan, S.; Gautier, D. C.; Johnson, R. P.; Shimada, T.; Fernandez, J. C.; Tsung, F. S.; Mori, W. B.

2017-10-01

Near critical density relativistic electron jets from laser solid interaction carry currents approaching the Alfvén-limit and tens of kilo-Tesla magnetic fields. Such jets are often found in kinetic simulations with low areal density targets, but have not been confirmed experimentally. They may be used for X/gamma-ray generation and is also important for the understanding of post-transparency plasma dynamics. With a short-pulse probe beam at the Trident laser facility, we employed proton deflectometry to infer the jet's properties, structure and the long-time dynamics. We develop corresponding GEANT4 simulation model of the proton deflectometry, with input from the kinetic PIC simulations in 2D and quasi-3D geometry, to compare with the experimental radiography images. Detail comparison of the experimental and simulation features in the deflectometry will be discussed. Work supported by the LDRD program at LANL.

46 CFR 132.120 - Fire pumps.

Code of Federal Regulations, 2011 CFR

2011-10-01

... with one self-priming power-driven fire pump capable of delivering a single stream of water from the..., the pump required by paragraph (a) of this section may be driven by one of the engines. If only one propulsion engine is installed, the pump must be driven by a source of power independent of the engine. (e...

46 CFR 132.120 - Fire pumps.

Code of Federal Regulations, 2012 CFR

2012-10-01

... vessel must be equipped with one self-priming power-driven fire pump capable of delivering a single... propulsion engines are installed, the pump required by paragraph (a) of this section may be driven by one of the engines. If only one propulsion engine is installed, the pump must be driven by a source of power...

46 CFR 132.120 - Fire pumps.

Code of Federal Regulations, 2014 CFR

2014-10-01

... vessel must be equipped with one self-priming power-driven fire pump capable of delivering a single... propulsion engines are installed, the pump required by paragraph (a) of this section may be driven by one of the engines. If only one propulsion engine is installed, the pump must be driven by a source of power...

46 CFR 132.120 - Fire pumps.

Code of Federal Regulations, 2013 CFR

2013-10-01

... vessel must be equipped with one self-priming power-driven fire pump capable of delivering a single... propulsion engines are installed, the pump required by paragraph (a) of this section may be driven by one of the engines. If only one propulsion engine is installed, the pump must be driven by a source of power...

The fifth electron in the fully reduced caa(3) from Thermus thermophilus is competent in proton pumping.

PubMed

Siletsky, Sergey A; Belevich, Ilya; Soulimane, Tewfik; Verkhovsky, Michael I; Wikström, Mårten

2013-01-01

The time-resolved kinetics of membrane potential generation coupled to oxidation of the fully reduced (five-electron) caa(3) cytochrome oxidase from Thermus thermophilus by oxygen was studied in a single-turnover regime. In order to calibrate the number of charges that move across the vesicle membrane in the different reaction steps, the reverse electron transfer from heme a(3) to heme a and further to the cytochrome c/Cu(A) has been resolved upon photodissociation of CO from the mixed valence enzyme in the absence of oxygen. The reverse electron transfer from heme a(3) to heme a and further to the cytochrome c/Cu(A) pair is resolved as a single transition with τ~40 μs. In the reaction of the fully reduced cytochrome caa(3) with oxygen, the first electrogenic phase (τ~30 μs) is linked to OO bond cleavage and generation of the P(R) state. The next electrogenic component (τ~50 μs) is associated with the P(R)→F transition and together with the previous reaction step it is coupled to translocation of about two charges across the membrane. The three subsequent electrogenic phases, with time constants of ~0.25 ms, ~1.4 ms and ~4 ms, are linked to the conversion of the binuclear center through the F→O(H)→E(H) transitions, and result in additional transfer of four charges through the membrane dielectric. This indicates that the delivery of the fifth electron from heme c to the binuclear center is coupled to pumping of an additional proton across the membrane. Copyright © 2012 Elsevier B.V. All rights reserved.

Tunable mega-ampere electron current propagation in solids by dynamic control of lattice melt

DOE PAGES

MacLellan, D.  A.; Carroll, D.  C.; Gray, R.  J.; ...

2014-10-31

The influence of lattice-melt-induced resistivity gradients on the transport of mega-ampere currents of fast electrons in solids is investigated numerically and experimentally using laser-accelerated protons to induce isochoric heating. Tailoring the heating profile enables the resistive magnetic fields which strongly influence the current propagation to be manipulated. This tunable laser-driven process enables important fast electron beam properties, including the beam divergence, profile, and symmetry to be actively tailored, and without recourse to complex target manufacture.

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.

PubMed

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.

Proton Radiography of Spontaneous Fields, Plasma Flows and Dynamics in X-Ray Driven Inertial-Confinement Fusion Implosions

NASA Astrophysics Data System (ADS)

Li, C. K.; Seguin, F. H.; Frenje, J. A.; Rosenberg, M.; Zylstra, A. B.; Rinderknecht, H. G.; Petrasso, R. D.; Amendt, P. A.; Landen, O. L.; Town, R. P. J.; Betti, R.; Knauer, J. P.; Meyerhofer, D. D.; Back, C. A.; Kilkenny, J. D.; Nikroo, A.

2010-11-01

Backlighting of x-ray-driven implosions in empty hohlraums with mono-energetic protons on the OMEGA laser facility has allowed a number of important phenomena to be observed. Several critical parameters were determined, including plasma flow, three types of spontaneous electric fields and megaGauss magnetic fields. These results provide insight into important issues in indirect-drive ICF. Even though the cavity is effectively a Faraday cage, the strong, local fields inside the hohlraum can affect laser-plasma instabilities, electron distributions and implosion symmetry. They are of fundamental scientific importance for a range of new experiments at the frontiers of high-energy-density physics. Future experiments designed to characterize the field formation and evolution in low-Z gas fill hohlraums will be discussed.

Cost-effectiveness of histamine receptor-2 antagonist versus proton pump inhibitor for stress ulcer prophylaxis in critically ill patients*.

PubMed

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 receptor-2 antagonists, but the survival benefit of 0.0167% favored proton pump inhibitors. Histamine receptor-2 antagonist therapy appears to reduce costs with survival benefit comparable to proton pump inhibitor therapy for stress ulcer prophylaxis. Ventilator-associated pneumonia and bleed are the variables most affecting these outcomes. The uncertainty in the findings justifies a prospective trial.

Light-driven Na + pump from Gillisia limnaea: A high-affinity Na + binding site is formed transiently in the photocycle

DOE PAGES

Balashov, Sergei P.; Imasheva, Eleonora S.; Dioumaev, Andrei K.; ...

2014-11-06

A group of microbial retinal proteins most closely related to the proton pump xanthorhodopsin has a novel sequence motif and a novel function. Instead of, or in addition to, proton transport, they perform light-driven sodium ion transport, as reported for one representative of this group (KR2) from Krokinobacter. In this paper, we examine a similar protein, GLR from Gillisia limnaea, expressed in Escherichia coli, which shares some properties with KR2 but transports only Na +. The absorption spectrum of GLR is insensitive to Na + at concentrations of ≤3 M. However, very low concentrations of Na + cause profound differencesmore » in the decay and rise time of photocycle intermediates, consistent with a switch from a “Na +-independent” to a “Na +-dependent” photocycle (or photocycle branch) at ~60 μM Na +. The rates of photocycle steps in the latter, but not the former, are linearly dependent on Na + concentration. This suggests that a high-affinity Na + binding site is created transiently after photoexcitation, and entry of Na + from the bulk to this site redirects the course of events in the remainder of the cycle. A greater concentration of Na + is needed for switching the reaction path at lower pH. The data suggest therefore competition between H + and Na + to determine the two alternative pathways. The idea that a Na + binding site can be created at the Schiff base counterion is supported by the finding that upon perturbation of this region in the D251E mutant, Na + binds without photoexcitation. Furthermore, binding of Na+ to the mutant shifts the chromophore maximum to the red like that of H +, which occurs in the photocycle of the wild type.« less

Overutilization of proton pump inhibitors: a review of cost-effectiveness and risk [corrected].

PubMed

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.

Proton Pumps: Mechanism of Action and Applications

NASA Technical Reports Server (NTRS)

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.

Design of a high-pressure circulating pump for viscous liquids.

PubMed

Seifried, Bernhard; Temelli, Feral

2009-07-01

The design of a reciprocating dual action piston pump capable of circulating viscous fluids at pressures of up to 34 MPa (5000 psi) and temperatures up to 80 degrees C is described. The piston of this pump is driven by a pair of solenoids energized alternatively by a 12 V direct current power supply controlled by an electronic controller facilitating continuously adjustable flow rates. The body of this seal-less pump is constructed using off-the-shelf parts eliminating the need for custom made parts. Both the electronic controller and the pump can be assembled relatively easily. Pump performance has been evaluated at room temperature (22 degrees C) and atmospheric pressure using liquids with low and moderately high viscosities, such as ethanol and corn oil, respectively. At ambient conditions, the pump delivered continuous flow of ethanol and corn oil at a flow rate of up to 170 and 17 cm3/min, respectively. For pumping viscous fluids comparable to corn oil, an optimum reciprocation frequency was ascertained to maximize flow rate. For low viscosity liquids such as ethanol, a linear relationship between the flow rate and reciprocation frequency was determined up to the maximum reciprocation frequency of the pump. Since its fabrication, the pump has been used in our laboratory for circulating triglycerides in contact with supercritical carbon dioxide at pressures of up to 25 MPa (3600 psi) and temperatures up to 70 degrees C on a daily basis for a total of more than 1500 h of operation functioning trouble free.

Meta-analysis: comparative efficacy of different proton-pump inhibitors in triple therapy for Helicobacter pylori eradication.

PubMed

Vergara, M; Vallve, M; Gisbert, J P; Calvet, X

2003-09-15

It is not known whether certain proton-pump inhibitors are more efficacious than others when used in triple therapy for Helicobacter pylori eradication. To compare the efficacy of different proton-pump inhibitors in triple therapy by performing a meta-analysis. A MEDLINE search was performed. Abstracts of the European Helicobacter pylori Study Group and the American Gastroenterological Association congresses from 1996 to 2002 were also examined. Randomized studies with at least two branches of triple therapy that differed only in terms of type of proton-pump inhibitor were included in a meta-analysis using Review Manager 4.1. Fourteen studies were included. Intention-to-treat cure rates were similar for omeprazole and lansoprazole: 74.7% vs. 76%, odds ratio (OR) 0.91 [95% confidence interval (CI) 0.69-1.21] in a total of 1085 patients; for omeprazole and rabeprazole: 77.9% vs. 81.2%, OR 0.81 (95% CI 0.58-1.15) in a total of 825 patients; for omeprazole and esomeprazole: 87.7% vs. 89%, OR 0.89 (95% CI 0.58-1.35) in 833 patients; and for lansoprazole and rabeprazole: 81% vs. 85.7%, OR 0.77 (95% CI 0.48-1.22) in 550 patients. The efficacy of various proton-pump inhibitors seems to be similar when used for H. pylori eradication in standard triple therapy.

Applications of Ultra-Intense, Short Laser Pulses

NASA Astrophysics Data System (ADS)

Ledingham, Ken W. D.

The high intensity laser production of electron, proton, ion and photon beams is reviewed particularly with respect to the laser-plasma interaction which drives the acceleration process. A number of applications for these intense short pulse beams is discussed e.g. ion therapy, PET isotope production and laser driven transmutation studies. The future for laser driven nuclear physics at the huge new, multi-petawatt proposed laser installation ELI in Bucharest is described. Many people believe this will take European nuclear research to the next level.

Acceleration and heating of two-fluid solar wind by Alfven waves

NASA Technical Reports Server (NTRS)

Sandbaek, Ornulf; Leer, Egil

1994-01-01

Earlier model studies of solar wind driven by thermal pressure and Alfven waves have shown that wave amplitudes of 20-30 km/s at the coronal base are sufficient to accelerate the flow to the high speeds observed in quasi-steady streams emanating from large coronal holes. We focus on the energy balance in the proton gas and show that heat conduction from the region where the waves are dissipated may play an important role in determining the proton temperature at the orbit of Earth. In models with 'classical' heat conduction we find a correlation between high flow speed, high proton temperature, and low electron temperature at 1 AU. The effect of wave heating on the development of anisotropies in the solar wind proton gas pressure is also investigated in this study.

Functional role of coenzyme Q in the energy coupling of NADH-CoQ oxidoreductase (Complex I): stabilization of the semiquinone state with the application of inside-positive membrane potential to proteoliposomes.

PubMed

Ohnishi, Tomoko; Ohnishi, S Tsuyoshi; Shinzawa-Ito, Kyoko; Yoshikawa, Shinya

2008-01-01

Coenzyme Q10 (which is also designated as CoQ10, ubiquinone-10, UQ10, CoQ, UQ or simply as Q) plays an important role in energy metabolism. For NADH-Q oxidoreductase (complex I), Ohnishi and Salerno proposed a hypothesis that the proton pump is operated by the redox-driven conformational change of a Q-binding protein, and that the bound form of semiquinone (SQ) serves as its gate [FEBS Letters 579 (2005) 45-55]. This was based on the following experimental results: (i) EPR signals of the fast-relaxing SQ anion (designated as QNf(.-)) are observable only in the presence of the proton electrochemical potential (DeltamuH+); (ii) iron-sulfur cluster N2 and QNf(.-) are directly spin-coupled; and (iii) their center-to-center distance was calculated as 12angstroms, but QNf(.-) is only 5angstroms deeper than N2 perpendicularly to the membrane. After the priming reduction of Q to QNf(.-), the proton pump operates only in the steps between the semiquinone anion (QNf(.-)) and fully reduced quinone (QH2). Thus, by cycling twice for one NADH molecule, the pump transports 4H+ per 2e(-). This hypothesis predicts the following phenomena: (a) Coupled with the piericidin A sensitive NADH-DBQ or Q1 reductase reaction, DeltamuH+ would be established; (b) DeltamuH+ would enhance the SQ EPR signals; and (c) the dissipation of DeltamuH+ with the addition of an uncoupler would increase the rate of NADH oxidation and decrease the SQ signals. We reconstituted bovine heart complex I, which was prepared at Yoshikawa's laboratory, into proteoliposomes. Using this system, we succeeded in demonstrating that all of these phenomena actually took place. We believe that these results strongly support our hypothesis.

The role of Rnf in ion gradient formation in Desulfovibrio alaskensis

DOE PAGES

Wang, Luyao; Bradstock, Peter; Li, Chuang; ...

2016-04-14

Rnf is a membrane protein complex that has been shown to be important in energy conservation. Here, Desulfovibrio alaskensis G20 and Rnf mutants of G20 were grown with different electron donor and acceptor combinations to determine the importance of Rnf in energy conservation and the type of ion gradient generated. The addition of the protonophore TCS strongly inhibited lactate-sulfate dependent growth whereas the sodium ionophore ETH2120 had no effect, indicating a role for the proton gradient during growth. Mutants in rnfA and rnfD were more sensitive to the protonophore at 5 µM than the parental strain, suggesting the importance ofmore » Rnf in the generation of a proton gradient. The electrical potential (ΔΨ), ΔpH and proton motive force were lower in thernfAmutant than in the parental strain of D.alaskensis G20. In conclusion, these results provide evidence that the Rnf complex in D. alaskensis functions as a primary proton pump whose activity is important for growth.« less

A pathway for protons in nitric oxide reductase from Paracoccus denitrificans.

PubMed

Reimann, Joachim; Flock, Ulrika; Lepp, Håkan; Honigmann, Alf; Adelroth, Pia

2007-05-01

Nitric oxide reductase (NOR) from P. denitrificans is a membrane-bound protein complex that catalyses the reduction of NO to N(2)O (2NO+2e(-)+2H(+)-->N(2)O+H(2)O) as part of the denitrification process. Even though NO reduction is a highly exergonic reaction, and NOR belongs to the superfamily of O(2)-reducing, proton-pumping heme-copper oxidases (HCuOs), previous measurements have indicated that the reaction catalyzed by NOR is non-electrogenic, i.e. not contributing to the proton electrochemical gradient. Since electrons are provided by donors in the periplasm, this non-electrogenicity implies that the substrate protons are also taken up from the periplasm. Here, using direct measurements in liposome-reconstituted NOR during reduction of both NO and the alternative substrate O(2), we demonstrate that protons are indeed consumed from the 'outside'. First, multiple turnover reduction of O(2) resulted in an increase in pH on the outside of the NOR-vesicles. Second, comparison of electrical potential generation in NOR-liposomes during oxidation of the reduced enzyme by either NO or O(2) shows that the proton transfer signals are very similar for the two substrates proving the usefulness of O(2) as a model substrate for these studies. Last, optical measurements during single-turnover oxidation by O(2) show electron transfer coupled to proton uptake from outside the NOR-liposomes with a tau=15 ms, similar to results obtained for net proton uptake in solubilised NOR [U. Flock, N.J. Watmough, P. Adelroth, Electron/proton coupling in bacterial nitric oxide reductase during reduction of oxygen, Biochemistry 44 (2005) 10711-10719]. NOR must thus contain a proton transfer pathway leading from the periplasmic surface into the active site. Using homology modeling with the structures of HCuOs as templates, we constructed a 3D model of the NorB catalytic subunit from P. denitrificans in order to search for such a pathway. A plausible pathway, consisting of conserved protonatable residues, is suggested.

Two-dimensional Nonlinear Simulations of Temperature-anisotropy Instabilities with a Proton-alpha Drift

NASA Astrophysics Data System (ADS)

Markovskii, S. A.; Chandran, Benjamin D. G.; Vasquez, Bernard J.

2018-04-01

We present two-dimensional hybrid simulations of proton-cyclotron and mirror instabilities in a proton-alpha plasma with particle-in-cell ions and a neutralizing electron fluid. The instabilities are driven by the protons with temperature perpendicular to the background magnetic field larger than the parallel temperature. The alpha particles with initially isotropic temperature have a nonzero drift speed with respect to the protons. The minor ions are known to influence the relative effect of the proton-cyclotron and mirror instabilities. In this paper, we show that the mirror mode can dominate the power spectrum at the nonlinear stage even if its linear growth rate is significantly lower than that of the proton-cyclotron mode. The proton-cyclotron instability combined with the alpha-proton drift is a possible cause of the nonzero magnetic helicity observed in the solar wind for fluctuations propagating nearly parallel to the magnetic field. Our simulations generally confirm this concept but reveal a complex helicity spectrum that is not anticipated from the linear theory of the instability.

Dual-channel current valve in a three terminal zigzag graphene nanoribbon junction

NASA Astrophysics Data System (ADS)

Zhang, L.

2017-02-01

We theoretically propose a dual-channel current valve based on a three terminal zigzag graphene nanoribbon (ZGNR) junction driven by three asymmetric time-dependent pumping potentials. By means of the Keldysh Green’s function method, we show that two asymmetric charge currents can be pumped in the different left-right terminals of the device at a zero bias, which mainly stems from the single photon-assisted pumping approximation and the valley valve effect in a ZGNR p-n junction. The ON and OFF states of pumped charge currents are crucially dependent on the even-odd chain widths of the three electrodes, the pumping frequency, the lattice potential and the Fermi level. Two-tunneling spin valves are also considered to spatially separate and detect 100% polarized spin currents owing to the combined spin pump effect and the valley selective transport in a three terminal ZGNR ferromagnetic junction. Our investigations might be helpful to control the spatial and spin degrees of freedom of electrons in graphene pumping devices.

Development of a tritium monitor combined with an electrochemical tritium pump using a proton conducting oxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanaka, M.; Sugiyama, T.

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 themore » proposed tritium monitoring system is that it is able to convert HTO into molecular hydrogen.« less

Natural Gas Engine-Driven Heat Pump Demonstration at DoD Installations: Performance and Reliability Summary

DTIC Science & Technology

2009-06-09

ER D C/ CE R L TR -0 9 -1 0 Natural Gas Engine-Driven Heat Pump Demonstration at DoD Installations Performance and Reliability Summary...L ab or at or y Approved for public release; distribution is unlimited. ERDC/CERL TR-09-10 June 2009 Natural Gas Engine-Driven Heat Pump ...CERL TR-09-10 ii Abstract: Results of field testing natural gas engine-driven heat pumps (GHP) at six southwestern U.S. Department of Defense (DoD

Electron, proton and hydrogen-atom transfers in photosynthetic water oxidation.

PubMed Central

Tommos, Cecilia

2002-01-01

When photosynthetic organisms developed so that they could use water as an electron source to reduce carbon dioxide, the stage was set for efficient proliferation. Algae and plants spread globally and provided the foundation for our atmosphere and for O(2)-based chemistry in biological systems. Light-driven water oxidation is catalysed by photosystem II, the active site of which contains a redox-active tyrosine denoted Y(Z), a tetramanganese cluster, calcium and chloride. In 1995, Gerald Babcock and co-workers presented the hypothesis that photosynthetic water oxidation occurs as a metallo-radical catalysed process. In this model, the oxidized tyrosine radical is generated by coupled proton/electron transfer and re-reduced by abstracting hydrogen atoms from substrate water or hydroxide-ligated to the manganese cluster. The proposed function of Y(Z) requires proton transfer from the tyrosine site upon oxidation. The oxidation mechanism of Y(Z) in an inhibited and O(2)-evolving photosystem II is discussed. Domino-deprotonation from Y(Z) to the bulk solution is shown to be consistent with a variety of data obtained on metal-depleted samples. Experimental data that suggest that the oxidation of Y(Z) in O(2)-evolving samples is coupled to proton transfer in a hydrogen-bonding network are described. Finally, a dielectric-dependent model for the proton release that is associated with the catalytic cycle of photosystem II is discussed. PMID:12437877

Femtosecond-pulse-driven electron-excited extreme-ultraviolet lasers in Be-like ions.

PubMed

Hooker, S M; Harris, S E

1995-10-01

A suggestion for the generation of extreme-ultraviolet (XUV) laser radiation based on tunneling ionization and subsequent electron excitation of Deltan not equal 0 transitions is described. The favorable scaling of the required intensity of the pump laser with the output XUV wavelength is compared with that exhibited by XUV lasers ased on Deltan = 0 transitions. Calculations for Be-like Ne predict signif icant gain at 14.1 nm.

Global MHD Simulation of the Coronal Mass Ejection on 2011 March 7: from Chromosphere to 1 AU

NASA Astrophysics Data System (ADS)

Jin, M.; Manchester, W.; van der Holst, B.; Oran, R.; Sokolov, I.; Toth, G.; Vourlidas, A.; Liu, Y.; Sun, X.; Gombosi, T. I.

2013-12-01

In this study, we present magnetohydrodynamics simulation results of a fast CME event that occurred on 2011 March 7 by using the newly developed Alfven Wave Solar Model (AWSoM) in Space Weather Modeling Framework (SWMF). The background solar wind is driven by Alfven-wave pressure and heated by Alfven-wave dissipation in which we have incorporated balanced turbulence at the top of the closed field lines. The magnetic field of the inner boundary is specified with a synoptic magnetogram from SDO/HMI. In order to produce the physically correct CME structures and CME-driven shocks, the electron and proton temperatures are separated so that the electron heat conduction is explicitly treated in conjunction with proton shock heating. Also, collisionless heat conduction is implemented for getting the correct electron temperature at 1 AU. We initiate the CME by using the Gibson-Low flux rope model and simulate the CME propagation to 1 AU. A comprehensive validation study is performed using remote as well as in-situ observations from SOHO, STEREOA/B, ACE, and WIND. Our result shows that the new model can reproduce most of the observed features and the arrival time of the CME is correctly estimated, which suggests the forecasting capability of the new model. We also examine the simulated CME-driven shock structures that are important for modeling the associated solar energetic event (SEP) with diffusive shock acceleration.

Boosting laser-ion acceleration with multi-picosecond pulses

PubMed Central

Yogo, A.; Mima, K.; Iwata, N.; Tosaki, S.; Morace, A.; Arikawa, Y.; Fujioka, S.; Johzaki, T.; Sentoku, Y.; Nishimura, H.; Sagisaka, A.; Matsuo, K.; Kamitsukasa, N.; Kojima, S.; Nagatomo, H.; Nakai, M.; Shiraga, H.; Murakami, M.; Tokita, S.; Kawanaka, J.; Miyanaga, N.; Yamanoi, K.; Norimatsu, T.; Sakagami, H.; Bulanov, S. V.; Kondo, K.; Azechi, H.

2017-01-01

Using one of the world most powerful laser facility, we demonstrate for the first time that high-contrast multi-picosecond pulses are advantageous for proton acceleration. By extending the pulse duration from 1.5 to 6 ps with fixed laser intensity of 1018 W cm−2, the maximum proton energy is improved more than twice (from 13 to 33 MeV). At the same time, laser-energy conversion efficiency into the MeV protons is enhanced with an order of magnitude, achieving 5% for protons above 6 MeV with the 6 ps pulse duration. The proton energies observed are discussed using a plasma expansion model newly developed that takes the electron temperature evolution beyond the ponderomotive energy in the over picoseconds interaction into account. The present results are quite encouraging for realizing ion-driven fast ignition and novel ion beamlines. PMID:28211913

Chimeric Proton-Pumping Rhodopsins Containing the Cytoplasmic Loop of Bovine Rhodopsin

PubMed Central

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

Structural insights into electron transfer in caa3-type cytochrome oxidase

PubMed Central

Lyons, Joseph A.; Aragão, David; Slattery, Orla; Pisliakov, Andrei V.; Soulimane, Tewfik; Caffrey, Martin

2012-01-01

Summary Paragraph Cytochrome c oxidase is a member of the heme copper oxidase superfamily (HCO)1. HCOs function as the terminal enzymes in the respiratory chain of mitochondria and aerobic prokaryotes, coupling molecular oxygen reduction to transmembrane proton pumping. Integral to the enzyme’s function is the transfer of electrons from cytochrome c to the oxidase via a transient association of the two proteins. Electron entry and exit are proposed to occur from the same site on cytochrome c2–4. Here we report the crystal structure of the caa3-type cytochrome oxidase from Thermus thermophilus, which has a covalently tethered cytochrome c domain. Crystals were grown in a bicontinuous mesophase using a synthetic short-chain monoacylglycerol as the hosting lipid. From the electron density map, at 2.36 Å resolution, a novel integral membrane subunit and a native glycoglycerophospholipid embedded in the complex were identified. Contrary to previous electron transfer mechanisms observed for soluble cytochrome c, the structure reveals the architecture of the electron transfer complex for the fused cupredoxin/cytochrome c domain which implicates different sites on cytochrome c for electron entry and exit. Support for an alternative to the classical proton gate characteristic of this HCO class is presented. PMID:22763450

Refrigerant charge management in a heat pump water heater

DOEpatents

Chen, Jie; Hampton, Justin W.

2014-06-24

Heat pumps that heat or cool a space and that also heat water, refrigerant management systems for such heat pumps, methods of managing refrigerant charge, and methods for heating and cooling a space and heating water. Various embodiments deliver refrigerant gas to a heat exchanger that is not needed for transferring heat, drive liquid refrigerant out of that heat exchanger, isolate that heat exchanger against additional refrigerant flowing into it, and operate the heat pump while the heat exchanger is isolated. The heat exchanger can be isolated by closing an electronic expansion valve, actuating a refrigerant management valve, or both. Refrigerant charge can be controlled or adjusted by controlling how much liquid refrigerant is driven from the heat exchanger, by letting refrigerant back into the heat exchanger, or both. Heat pumps can be operated in different modes of operation, and segments of refrigerant conduit can be interconnected with various components.

Dynamical instability of a driven-dissipative electron-hole condensate in the BCS-BEC crossover region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanai, Ryo; Littlewood, Peter B.; Ohashi, Yoji

2017-09-01

We present a stability analysis on a driven-dissipative electron-hole condensate in the BCS (Bardeen-Cooper-Schrieffer)-BEC (Bose-Einstein-condensation)-crossover region. Extending the combined BCS-Leggett theory with the generalized random phase approximation (GRPA) to the non-equilibrium case by employing the Keldysh formalism, we show that the pumping-and-decay of carriers causes a depairing effect on excitons. This phenomenon gives rise to an attractive interaction between excitons in the BEC regime, as well as a supercurrent that anomalously flows anti-parallel to ∇θ(r) (where θ(r) is the phase of the condensate) in the BCS regime, both leading to dynamical instabilities of an exciton-BEC.

Construction of a magnetic bottle spectrometer and its application to pulse duration measurement of X-ray laser using a pump-probe method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Namba, S., E-mail: namba@hiroshima-u.ac.jp; Hasegawa, N.; Kishimoto, M.

To characterize the temporal evolution of ultrashort X-ray pulses emitted by laser plasmas using a pump-probe method, a magnetic bottle time-of-flight electron spectrometer is constructed. The design is determined by numerical calculations of a mirror magnetic field and of the electron trajectory in a flight tube. The performance of the spectrometer is characterized by measuring the electron spectra of xenon atoms irradiated with a laser-driven plasma X-ray pulse. In addition, two-color above-threshold ionization (ATI) experiment is conducted for measurement of the X-ray laser pulse duration, in which xenon atoms are simultaneously irradiated with an X-ray laser pump and an IRmore » laser probe. The correlation in the intensity of the sideband spectra of the 4d inner-shell photoelectrons and in the time delay of the two laser pulses yields an X-ray pulse width of 5.7 ps, in good agreement with the value obtained using an X-ray streak camera.« less

Performance of a vane driven-gear pump

NASA Technical Reports Server (NTRS)

Heald, R H

1921-01-01

Given here are the results of a test conducted in a wind tunnel on the performance of a vane-driven gear pump used to pump gasoline upward into a small tank located within the upper wing from which it flows by gravity to the engine carburetor. Information is given on the efficiency of the pump, the head resistance of the vanes, the performance and characteristics of the unit with and without housing about the vanes, the pump performance when motor driven, and resistance and power characteristics.

Molecular basis of proton uptake in single and double mutants of cytochrome c oxidase

NASA Astrophysics Data System (ADS)

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 of long-range electrostatic forces and local structural fluctuations in the control of proton movement and provide a physical explanation for the restoration of proton pumping activity in the double mutant.

18. Electrically driven pumps in Armory Street Pump House. Pumps ...

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

18. Electrically driven pumps in Armory Street Pump House. Pumps in background formerly drew water from the clear well. They went out of service when use of the beds was discontinued. Pumps in the foreground provide high pressure water to Hamden. - Lake Whitney Water Filtration Plant, Armory Street Pumphouse, North side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

Conjecture regarding posttranslational modifications to the arabidopsis type I proton-pumping pyrophosphatase (AVP1)

USDA-ARS?s Scientific Manuscript database

Agbiotechnology uses genetic engineering to improve the output and value of crops. Altering the expression of the plant Type I Proton-pumping Pyrophosphatase (H+-PPase) has already proven to be a useful tool to enhance crop productivity. Despite the effective use of this gene in translational resear...

Surgery and proton pump inhibitors for treatment of vocal process granulomas.

PubMed

Hong-Gang, Duan; He-Juan, Jin; Chun-Quan, Zheng; Guo-Kang, Fan

2013-11-01

The aim of this study was to analyze the outcomes of vocal process granulomas treated with surgery and proton pump inhibitors and to specify related factors of recurrence. The medical records of patients with diagnosis of vocal process granuloma between 2000 and 2012 were reviewed. All patients were treated with surgery and proton pump inhibitors for at least 1 month. Forty-one patients were reviewed; mean follow-up time was 45 months. There was no recurrence among the patients who had a recent history of intubation. The recurrence rates of contact granuloma was 38.7 %, and significantly related to the frequency of surgery (P = 0.042), but was not significantly associated with the history of acid reflux (P = 0.676) and vocal abuse (P = 0.447), lesion size (P = 0.203) or surgical techniques (P = 0.331). Surgery combined with proton pump inhibitors was partially effective for the vocal process granulomas, especially with intubated patients. However, repeat surgery for recurrent contact granuloma should be preceded with caution due to high recurrence rates.

Proton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy.

PubMed

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.

Decrease in Switches to 'Unsafe' Proton Pump Inhibitors After Communications About Interactions with Clopidogrel.

PubMed

Kruik-Kollöffel, Willemien J; van der Palen, Job; van Herk-Sukel, Myrthe P P; Kruik, H Joost; Movig, Kris L L

2017-08-01

In 2009 and 2010 medicines regulatory agencies published official safety statements regarding the concomitant use of proton pump inhibitors and clopidogrel. We wanted to investigate a change in prescription behaviour in prevalent gastroprotective drug users (2008-2011). Data on drug use were retrieved from the Out-patient Pharmacy Database of the PHARMO Database Network. We used interrupted time series analyses (ITS) to estimate the impact of each safety statement on the number of gastroprotective drug switches around the start of clopidogrel and during clopidogrel use. After the first statement (June 2009), significantly fewer patients switched from another proton pump inhibitor to (es)omeprazole (-14.9%; 95% CI -22.6 to -7.3) at the moment they started clopidogrel compared to the period prior to this statement. After the adjusted statement in February 2010, the switch percentage to (es)omeprazole decreased further (-4.5%; 95% CI -8.1 to -0.9). We observed a temporary increase in switches from proton pump inhibitors to histamine 2-receptor antagonists after the first statement; the decrease in the reverse switch was statistically significant (-23.0%; 95% CI -43.1 to -2.9). With ITS, we were able to demonstrate a decrease in switches from other proton pump inhibitors to (es)omeprazole and an increase of the reverse switch to almost 100%. We observed a partial and temporary switch to histamine 2-receptor antagonists. This effect of safety statements was shown for gastroprotective drug switches around the start of clopidogrel treatment.

Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study

PubMed Central

Grove, Erik L; Hansen, Peter Riis; Olesen, Jonas B; Ahlehoff, Ole; Selmer, Christian; Lindhardsen, Jesper; Madsen, Jan Kyst; Køber, Lars; Torp-Pedersen, Christian; Gislason, Gunnar H

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 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 death. The hazard ratio for the combined end point in patients receiving proton pump inhibitors based on the time dependent Cox proportional hazard model was 1.46 (1.33 to 1.61; P<0.001) and for the propensity score matched model based on 8318 patients it was 1.61 (1.45 to 1.79; P<0.001). A sensitivity analysis showed no increase in risk related to use of H2 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. PMID:21562004

Systematic review: proton pump inhibitors (PPIs) for the healing of reflux oesophagitis - a comparison of esomeprazole with other PPIs.

PubMed

Edwards, S J; Lind, T; Lundell, L

2006-09-01

No randomized controlled trial has compared all the licensed standard dose proton pump inhibitors in the healing of reflux oesophagitis. To compare the effectiveness of esomeprazole with licensed standard dose proton pump inhibitors for healing of reflux oesophagitis (i.e. lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg). Systematic review of CENTRAL, BIOSIS, EMBASE and MEDLINE for randomized controlled trials in patients with reflux oesophagitis. Searching was completed in February 2005. Data on endoscopic healing rates at 4 and 8 weeks were extracted and re-analysed if not analysed by intention-to-treat. Meta-analysis was conducted using a fixed effects model. Of 133 papers identified in the literature search, six were of sufficient quality to be included in the analysis. No studies were identified comparing rabeprazole with esomeprazole. A meta-analysis of healing rates of esomeprazole 40 mg compared with standard dose proton pump inhibitors gave the following results: at 4 weeks [relative risk (RR) 0.92; 95% CI: 0.90, 0.94; P < 0.00001], and 8 weeks (RR 0.95; 95% CI: 0.94, 0.97; P < 0.00001). Publication bias did not have a significant impact on the results. The results were robust to changes in the inclusion/exclusion criteria and using a random effects model. Esomeprazole consistently demonstrates higher healing rates when compared with standard dose proton pump inhibitors.

Prolonged utilization of proton pump inhibitors in patients with ischemic and valvular heart disease is associated with surgical treatments, weight loss and aggravates anemia.

PubMed

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; p<0.001) and PCI 0.15 (CI: 0.10-0.22; p<0.001). The odds for having proton pump inhibitor in their chronic therapy were increased for atrial fibrillation 1.87 (CI: 1.08-3.23; p=0.025) and decreased for obesity 0.65 (CI: 0.45-0.96; p=0.035); surviving myocardial infarction 0.49 (CI: 0.29-0.83; p=0.035). Multinomial logistic regression controlled for existence of chronic renal disease found no significant association of renal dysfunction and PPI therapy. The existence of anemia was significantly increased in patients taking PPIs than controls; 6.00 (CI: 3.85-9.33; p<0.001). The use of PPI was also associated with worsening of metabolic profile, in part due to decreased utilization of ACE-inhibitors and statins. PPI consumption correlated with age of patients (Rho=0.216; p<0.001). High proportion of cardiovascular, particularly surgical patients with ischemic and valvular 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.

Mechanism and energetics by which glutamic acid 242 prevents leaks in cytochrome c oxidase.

PubMed

Kaila, Ville R I; Verkhovsky, Michael I; Hummer, Gerhard; Wikström, Mårten

2009-10-01

Cytochrome c oxidase (CcO) is the terminal enzyme of aerobic respiration. The energy released from the reduction of molecular oxygen to water is used to pump protons across the mitochondrial or bacterial membrane. The pump function introduces a mechanistic requirement of a valve that prevents protons from flowing backwards during the process. It was recently found that Glu-242, a key amino acid in transferring protons to be pumped across the membrane and to the site of oxygen reduction, fulfils the function of such a valve by preventing simultaneous contact to the pump site and to the proton-conducting D-channel (Kaila V.R.I. et al. Proc. Natl. Acad. Sci. USA 105, 2008). Here we have incorporated the valve model into the framework of the reaction mechanism. The function of the Glu valve is studied by exploring how the redox state of the surrounding metal centers, dielectric effects, and membrane potential, affects the energetics and leaks of this valve. Parallels are drawn between the dynamics of Glu-242 and the long-standing obscure difference between the metastable O(H) and stable O states of the binuclear center. Our model provides a suggestion for why reduction of the former state is coupled to proton translocation while reduction of the latter is not.

Miniature chemical ionization mass spectrometer for light aircraft measurements of tropospheric ammonia

NASA Astrophysics Data System (ADS)

Silver, J. A.; Bomse, D. S.; Massick, S. M.; Zondlo, M. A.

2003-12-01

Tropospheric ammonia plays important roles in the nucleation, growth, composition, and chemistry of aerosol particles. Unfortunately, high frequency and sensitive measurements of gas phase ammonia are lacking in most airborne-based field campaigns. Chemical ionization mass spectrometers (CIMS) have shown great promise for ammonia measurements, but CIMS instruments typically consume large amounts of power, are highly labor intensive, and are very heavy for most airborne platforms. These characteristics of CIMS instruments severely limit their potential deployment on smaller and lighter aircraft, despite the strong desire for ammonia measurements in atmospheric chemistry field campaigns. To this end, a CIMS ammonia instrument for light aircraft is being developed using a double-focusing, miniature mass spectrometer. The size of the mass spectrometer, comparable to a small apple, allows for higher operating pressures (0.1 mTorr) and lower pumping requirements. Power usage, including pumps and electronics, is estimated to be around 300 W, and the overall instrument including pumps, electronics, and permeation cells is expected to be about the size of a small monitor. The ion source uses americium-241 to generate protonated water ions which proton transfer to form ammonium ions. The ion source is made with commercially available ion optics to minimize machining costs. Mass spectra over its working range (~ 5-120 amu) are well represented by Gaussian shaped peaks. By examining the peak widths as a function of mass location, the resolution of the instrument was determined experimentally to be around 110 (m/delta m). The sensitivity, selectivity, power requirements, size, and performance characteristics of the miniature mass spectrometer will be described along with the possibilities for CIMS measurements on light aircraft.

ANTISECRETORY TREATMENT FOR PEDIATRIC GASTROESOPHAGEAL REFLUX DISEASE - A SYSTEMATIC REVIEW.

PubMed

Mattos, Ângelo Zambam de; Marchese, Gabriela Meirelles; Fonseca, Bárbara Brum; Kupski, Carlos; Machado, Marta Brenner

2017-12-01

Proton pump inhibitors and histamine H2 receptor antagonists are two of the most commonly prescribed drug classes for pediatric gastroesophageal reflux disease, but their efficacy is controversial. Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux, even that causal relation is not proven. To evaluate the use of proton pump inhibitors and histamine H2 receptor antagonists in pediatric gastroesophageal reflux disease through a systematic review. A systematic review was performed, using MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. The search was limited to studies published in English, Portuguese or Spanish. There was no limitation regarding date of publication. Studies were considered eligible if they were randomized-controlled trials, evaluating proton pump inhibitors and/or histamine H2 receptor antagonists for the treatment of pediatric gastroesophageal reflux disease. Studies published only as abstracts, studies evaluating only non-clinical outcomes and studies exclusively comparing different doses of the same drug were excluded. Data extraction was performed by independent investigators. The study protocol was registered at PROSPERO platform (CRD42016040156). After analyzing 735 retrieved references, 23 studies (1598 randomized patients) were included in the systematic review. Eight studies demonstrated that both proton pump inhibitors and histamine H2 receptor antagonists were effective against typical manifestations of gastroesophageal reflux disease, and that there was no evidence of benefit in combining the latter to the former or in routinely prescribing long-term maintenance treatments. Three studies evaluated the effect of treatments on children with asthma, and neither proton pump inhibitors nor histamine H2 receptor antagonists proved to be significantly better than placebo. One study compared different combinations of omeprazole, bethanechol and placebo for the treatment of children with cough, and there is no clear definition on the best strategy. Another study demonstrated that omeprazole performed better than ranitidine for the treatment of extraesophageal reflux manifestations. Ten studies failed to demonstrate significant benefits of proton pump inhibitors or histamine H2 receptor antagonists for the treatment of unspecific manifestations attributed to gastroesophageal reflux in infants. Proton pump inhibitors or histamine H2 receptor antagonists may be used to treat children with gastroesophageal reflux disease, but not to treat asthma or unspecific symptoms.

Interchange Instability and Transport in Matter-Antimatter Plasmas

NASA Astrophysics Data System (ADS)

Kendl, Alexander; Danler, Gregor; Wiesenberger, Matthias; Held, Markus

2017-06-01

Symmetric electron-positron plasmas in inhomogeneous magnetic fields are intrinsically subject to interchange instability and transport. Scaling relations for the propagation velocity of density perturbations relevant to transport in isothermal magnetically confined electron-positron plasmas are deduced, including damping effects when Debye lengths are large compared to Larmor radii. The relations are verified by nonlinear full-F gyrofluid computations. Results are analyzed with respect to planned magnetically confined electron-positron plasma experiments. The model is generalized to other matter-antimatter plasmas. Magnetized electron-positron-proton-antiproton plasmas are susceptible to interchange-driven local matter-antimatter separation, which can impede sustained laboratory magnetic confinement.

Interchange Instability and Transport in Matter-Antimatter Plasmas.

PubMed

Kendl, Alexander; Danler, Gregor; Wiesenberger, Matthias; Held, Markus

2017-06-09

Symmetric electron-positron plasmas in inhomogeneous magnetic fields are intrinsically subject to interchange instability and transport. Scaling relations for the propagation velocity of density perturbations relevant to transport in isothermal magnetically confined electron-positron plasmas are deduced, including damping effects when Debye lengths are large compared to Larmor radii. The relations are verified by nonlinear full-F gyrofluid computations. Results are analyzed with respect to planned magnetically confined electron-positron plasma experiments. The model is generalized to other matter-antimatter plasmas. Magnetized electron-positron-proton-antiproton plasmas are susceptible to interchange-driven local matter-antimatter separation, which can impede sustained laboratory magnetic confinement.

A bioenergetic basis for membrane divergence in archaea and bacteria.

PubMed

Sojo, Víctor; Pomiankowski, Andrew; Lane, Nick

2014-08-01

Membrane bioenergetics are universal, yet the phospholipid membranes of archaea and bacteria-the deepest branches in the tree of life-are fundamentally different. This deep divergence in membrane chemistry is reflected in other stark differences between the two domains, including ion pumping and DNA replication. We resolve this paradox by considering the energy requirements of the last universal common ancestor (LUCA). We develop a mathematical model based on the premise that LUCA depended on natural proton gradients. Our analysis shows that such gradients can power carbon and energy metabolism, but only in leaky cells with a proton permeability equivalent to fatty acid vesicles. Membranes with lower permeability (equivalent to modern phospholipids) collapse free-energy availability, precluding exploitation of natural gradients. Pumping protons across leaky membranes offers no advantage, even when permeability is decreased 1,000-fold. We hypothesize that a sodium-proton antiporter (SPAP) provided the first step towards modern membranes. SPAP increases the free energy available from natural proton gradients by ∼60%, enabling survival in 50-fold lower gradients, thereby facilitating ecological spread and divergence. Critically, SPAP also provides a steadily amplifying advantage to proton pumping as membrane permeability falls, for the first time favoring the evolution of ion-tight phospholipid membranes. The phospholipids of archaea and bacteria incorporate different stereoisomers of glycerol phosphate. We conclude that the enzymes involved took these alternatives by chance in independent populations that had already evolved distinct ion pumps. Our model offers a quantitatively robust explanation for why membrane bioenergetics are universal, yet ion pumps and phospholipid membranes arose later and independently in separate populations. Our findings elucidate the paradox that archaea and bacteria share DNA transcription, ribosomal translation, and ATP synthase, yet differ in equally fundamental traits that depend on the membrane, including DNA replication.

Duodenal ulcer and gastroesophageal reflux disease today: long-term therapy--a sideways glance.

PubMed Central

Bardhan, K. D.

1996-01-01

Acid-peptic disease is widely considered conquered or controlled, future advances being refinements of existing treatments rather than radical new developments. Yet controversies remain and developments have yet to be made. DUODENAL ULCER: Daily maintenance treatment with the anti-secretory drugs, histamine H2 receptor antagonists and proton pump blockers, controls duodenal ulcer effectively, markedly reducing relapse rate at one year after treatment from about 75 percent to 15 to 20 percent (and to about 10 percent on proton pump blockers). In contrast, Helicobacter pylori eradication with a one to two week course of treatment yields prolonged remission or cure. The consequent reduction in drug costs in individual patients, however, has been exceeded by increasing community use on the more expensive proton pump blockers for the treatment of gastroesophageal reflux disease. The marked decline in elective surgery since the introduction of histamine H2 receptor antagonists is commonly attributed to the power of these drugs. The fall, however, had started much earlier, indicating that the decline is due to changing natural history. In contrast, complication rates remain unaltered. An increasing proportion of newly diagnosed duodenal ulcer patients are elderly, and more of them now present for the first time with complications (in this center, about 40 percent), which consequently cannot be forestalled. Thus, duodenal ulcer disease is likely to remain a problem and in many will be a serious illness. GASTROESOPHAGEAL REFLUX DISEASE: The proton pump blockers have revolutionized the treatment of gastroesophageal reflux disease. In clinical trials they have proven markedly superior to the histamine H2 receptor antagonists in healing (at eight weeks, 80 to 90 percent vs. 50 to 60 percent), symptom relief, prevention of relapse on maintenance therapy and cost-effectiveness. However, several issues remain. The prevalence of gastroesophageal reflux disease seems to be rising and is now probably the commonest acid-peptic disease encountered in the West. Most clinical trials comparing proton pump blockers vs. histamine H2 receptor antagonists have been done in patients with erosive esophagitis, whereas the majority (50 to 60 percent) of patients with gastroesophageal reflux disease have milder, generally non-erosive, disease. The therapeutic gain of proton pump blockers diminishes in mild disease so may not be worth the higher drug costs. This is an important area for investigation. The majority of patients with erosive esophagitis relapse when treatment is stopped (about 75 percent at one year). Relapse is markedly reduced (to 20 to 25 percent) by daily maintenance treatment with proton pump blockers. Mild disease relapses less often, so longterm therapy by intermittent treatment may prove acceptable and more cost-effective than maintenance treatment. This strategy remains unexplored in trials. The ideal profile of an anti-secretory drug for intermittent treatment would combine rapid onset of action (similar to histamine H2 receptor antagonists) with powerful effect (as with proton pump blockers). The new class of drug, the reversible proton pump blocker (e.g., BY841) approaches this requirement. PMID:9165690

Space Station - The base for tomorrow's electronic industry

NASA Technical Reports Server (NTRS)

Naumann, Robert J.

1985-01-01

The potential value of space material processing on the Space Station for the electronics industry is examined. The primary advantages of the space environment for producing high-purity semiconductors and electrooptical materials are identified as the virtual absence of gravity (suppressing buoyancy-driven convection in melts and density segregation of alloys) and the availabilty of high vacuum (with high pumping speed and heat rejection). The recent history of material development and processing technology in the electronics industry is reviewed, and the principal features of early space experiments are outlined.

GHz laser-free time-resolved transmission electron microscopy: A stroboscopic high-duty-cycle method.

PubMed

Qiu, Jiaqi; Ha, Gwanghui; Jing, Chunguang; Baryshev, Sergey V; Reed, Bryan W; Lau, June W; Zhu, Yimei

2016-02-01

A device and a method for producing ultrashort electron pulses with GHz repetition rates via pulsing an input direct current (dc) electron beam are provided. The device and the method are based on an electromagnetic-mechanical pulser (EMMP) that consists of a series of transverse deflecting cavities and magnetic quadrupoles. The EMMP modulates and chops the incoming dc electron beam and converts it into pico- and sub-pico-second electron pulse sequences (pulse trains) at >1GHz repetition rates, as well as controllably manipulates the resulting pulses. Ultimately, it leads to negligible electron pulse phase-space degradation compared to the incoming dc beam parameters. The temporal pulse length and repetition rate for the EMMP can be continuously tunable over wide ranges. Applying the EMMP to a transmission electron microscope (TEM) with any dc electron source (e.g. thermionic, Schottky, or field-emission source), a GHz stroboscopic high-duty-cycle TEM can be realized. Unlike in many recent developments in time-resolved TEM that rely on a sample pumping laser paired with a laser launching electrons from a photocathode to probe the sample, there is no laser in the presented experimental set-up. This is expected to be a significant relief for electron microscopists who are not familiar with laser systems. The EMMP and the sample are externally driven by a radiofrequency (RF) source synchronized through a delay line. With no laser pumping the sample, the problem of the pump laser induced residual heating/damaging the sample is eliminated. As many RF-driven processes can be cycled indefinitely, sampling rates of 1-50GHz become accessible. Such a GHz stroboscopic TEM would open up a new paradigm for in situ and in operando experiments to study samples externally driven electromagnetically. Complementary to the lower (MHz) repetition rates experiments enabled by laser photocathode TEM, new experiments in the multi-GHz regime will be enabled by the proposed RF design. Because TEM is also a platform for various analytical methods, there are infinite application opportunities in energy and electronics to resolve charge (electronic and ionic) transport, and magnetic, plasmonic and excitonic dynamics in advanced functional materials. In addition, because the beam duty-cycle can be as high as ~10(-1) (or 10%), detection can be accomplished by commercially available detectors. In this article, we report an optimal design of the EMMP. The optimal design was found using an analytical generalized matrix approach in the thin lens approximation along with detailed beam dynamics taking actual realistic dc beam parameters in a TEM operating at 200keV. Copyright © 2015 Elsevier B.V. All rights reserved.

Ancient Living Organisms Escaping from, or Imprisoned in, the Vents?

PubMed Central

Jackson, J. Baz

2017-01-01

We have recently criticised the natural pH gradient hypothesis which purports to explain how the difference in pH between fluid issuing from ancient alkali vents and the more acidic Hadean ocean could have driven molecular machines that catalyse reactions that are useful in prebiotic and autotrophic chemistry. In this article, we temporarily suspend our earlier criticism while we consider difficulties for primitive organisms to have managed their energy supply and to have left the vents and become free-living. We point out that it may have been impossible for organisms to have acquired membrane-located proton (or sodium ion) pumps to replace the natural pH gradient, and independently to have driven essential molecular machines such as the ATP synthase. The volumes of the ocean and of the vent fluids were too large for a membrane-located pump to have generated a significant ion concentration gradient. Our arguments apply to three of the four concurrent models employed by the proponents of the natural pH gradient hypothesis. A fourth model is exempt from these arguments but has other intrinsic difficulties that we briefly consider. We conclude that ancient organisms utilising a natural pH gradient would have been imprisoned in the vents, unable to escape and become free-living. PMID:28914790

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

PubMed

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.

Physics at the SPS.

PubMed

Gatignon, L

2018-05-01

The CERN Super Proton Synchrotron (SPS) has delivered a variety of beams to a vigorous fixed target physics program since 1978. In this paper, we restrict ourselves to the description of a few illustrative examples in the ongoing physics program at the SPS. We will outline the physics aims of the COmmon Muon Proton Apparatus for Structure and Spectroscopy (COMPASS), north area 64 (NA64), north area 62 (NA62), north area 61 (NA61), and advanced proton driven plasma wakefield acceleration experiment (AWAKE). COMPASS studies the structure of the proton and more specifically of its spin. NA64 searches for the dark photon A', which is the messenger for interactions between normal and dark matter. The NA62 experiment aims at a 10% precision measurement of the very rare decay K + → π + νν. As this decay mode can be calculated very precisely in the Standard Model, it offers a very good opportunity to look for new physics beyond the Standard Model. The NA61/SHINE experiment studies the phase transition to Quark Gluon Plasma, a state in which the quarks and gluons that form the proton and the neutron are de-confined. Finally, AWAKE investigates proton-driven wake field acceleration: a promising technique to accelerate electrons with very high accelerating gradients. The Physics Beyond Colliders study at CERN is paving the way for a significant and diversified continuation of this already rich and compelling physics program that is complementary to the one at the big colliders like the Large Hadron Collider.

Physics at the SPS

NASA Astrophysics Data System (ADS)

Gatignon, L.

2018-05-01

The CERN Super Proton Synchrotron (SPS) has delivered a variety of beams to a vigorous fixed target physics program since 1978. In this paper, we restrict ourselves to the description of a few illustrative examples in the ongoing physics program at the SPS. We will outline the physics aims of the COmmon Muon Proton Apparatus for Structure and Spectroscopy (COMPASS), north area 64 (NA64), north area 62 (NA62), north area 61 (NA61), and advanced proton driven plasma wakefield acceleration experiment (AWAKE). COMPASS studies the structure of the proton and more specifically of its spin. NA64 searches for the dark photon A', which is the messenger for interactions between normal and dark matter. The NA62 experiment aims at a 10% precision measurement of the very rare decay K+ → π+νν. As this decay mode can be calculated very precisely in the Standard Model, it offers a very good opportunity to look for new physics beyond the Standard Model. The NA61/SHINE experiment studies the phase transition to Quark Gluon Plasma, a state in which the quarks and gluons that form the proton and the neutron are de-confined. Finally, AWAKE investigates proton-driven wake field acceleration: a promising technique to accelerate electrons with very high accelerating gradients. The Physics Beyond Colliders study at CERN is paving the way for a significant and diversified continuation of this already rich and compelling physics program that is complementary to the one at the big colliders like the Large Hadron Collider.

PIC simulation of a thermal anisotropy-driven Weibel instability in a circular rarefaction wave

NASA Astrophysics Data System (ADS)

Dieckmann, M. E.; Sarri, G.; Murphy, G. C.; Bret, A.; Romagnani, L.; Kourakis, I.; Borghesi, M.; Ynnerman, A.; O'C Drury, L.

2012-02-01

The expansion of an initially unmagnetized planar rarefaction wave has recently been shown to trigger a thermal anisotropy-driven Weibel instability (TAWI), which can generate magnetic fields from noise levels. It is examined here whether the TAWI can also grow in a curved rarefaction wave. The expansion of an initially unmagnetized circular plasma cloud, which consists of protons and hot electrons, into a vacuum is modelled for this purpose with a two-dimensional particle-in-cell (PIC) simulation. It is shown that the momentum transfer from the electrons to the radially accelerating protons can indeed trigger a TAWI. Radial current channels form and the aperiodic growth of a magnetowave is observed, which has a magnetic field that is oriented orthogonal to the simulation plane. The induced electric field implies that the electron density gradient is no longer parallel to the electric field. Evidence is presented here that this electric field modification triggers a second magnetic instability, which results in a rotational low-frequency magnetowave. The relevance of the TAWI is discussed for the growth of small-scale magnetic fields in astrophysical environments, which are needed to explain the electromagnetic emissions by astrophysical jets. It is outlined how this instability could be examined experimentally.

Identification of proton-pump inhibitor drugs that inhibit Trichomonas vaginalis uridine nucleoside ribohydrolase.

PubMed

Shea, Tara A; Burburan, Paola J; Matubia, Vivian N; Ramcharan, Sandy S; Rosario, Irving; Parkin, David W; Stockman, Brian J

2014-02-15

Trichomonas vaginalis continues to be a major health problem with drug-resistant strains increasing in prevalence. Novel antitrichomonal agents that are mechanistically distinct from current therapies are needed. The NIH Clinical Compound Collection was screened to find inhibitors of the uridine ribohydrolase enzyme required by the parasite to scavenge uracil for its growth. The proton-pump inhibitors omeprazole, pantoprazole, and rabeprazole were identified as inhibitors of this enzyme, with IC50 values ranging from 0.3 to 14.5 μM. This suggests a molecular mechanism for the in vitro antitrichomonal activity of these proton-pump inhibitors, and may provide important insights toward structure-based drug design. Copyright © 2014 Elsevier Ltd. All rights reserved.

The management of gastro-oesophageal reflux disease.

PubMed

Keung, Charlotte; Hebbard, Geoffrey

2016-02-01

If there are no features of serious disease, suspected gastro-oesophageal reflux disease can be initially managed with a trial of a proton pump inhibitor for 4-8 weeks. This should be taken 30-60 minutes before food for optimal effect. Once symptoms are controlled, attempt to withdraw acid suppression therapy. If symptoms recur, use the minimum dose that controls symptoms. Patients who have severe erosive oesophagitis, scleroderma oesophagus or Barrett's oesophagus require long-term treatment with a proton pump inhibitor. Lifestyle modification strategies can help gastro-oesophageal reflux disease. Weight loss has the strongest evidence for efficacy. Further investigation and a specialist referral are required if there is no response to proton pump inhibitor therapy. Atypical symptoms or signs of serious disease also need investigation.

Proton velocity ring-driven instabilities and their dependence on the ring speed: Linear theory

NASA Astrophysics Data System (ADS)

Min, Kyungguk; Liu, Kaijun; Gary, S. Peter

2017-08-01

Linear dispersion theory is used to study the Alfvén-cyclotron, mirror and ion Bernstein instabilities driven by a tenuous (1%) warm proton ring velocity distribution with a ring speed, vr, varying between 2vA and 10vA, where vA is the Alfvén speed. Relatively cool background protons and electrons are assumed. The modeled ring velocity distributions are unstable to both the Alfvén-cyclotron and ion Bernstein instabilities whose maximum growth rates are roughly a linear function of the ring speed. The mirror mode, which has real frequency ωr=0, becomes the fastest growing mode for sufficiently large vr/vA. The mirror and Bernstein instabilities have maximum growth at propagation oblique to the background magnetic field and become more field-aligned with an increasing ring speed. Considering its largest growth rate, the mirror mode, in addition to the Alfvén-cyclotron mode, can cause pitch angle diffusion of the ring protons when the ring speed becomes sufficiently large. Moreover, because the parallel phase speed, v∥ph, becomes sufficiently small relative to vr, the low-frequency Bernstein waves can also aid the pitch angle scattering of the ring protons for large vr. Potential implications of including these two instabilities at oblique propagation on heliospheric pickup ion dynamics are discussed.

[Do opioids, sedatives and proton-pump inhibitors increase the risk of fractures?

PubMed

Thorsdottir, Gudlaug; Benedikz, Elisabet; Thorgeirsdottir, Sigridur A; Johannsson, Magnus

2017-01-01

A pharmacoepidemiological study was conducted to analyse the relationship between bone fracture and the use of certain drugs. The study includes patients 40 years and older, diagnosed with bone fractures in the Emergency Department of Landspitali University Hospital in Reykjavik, Iceland, during a 10-year period (2002-2011). Also were included those who picked up from a pharmacy 90 DDD or more per year of the drugs included in the study in the capital region of Iceland during same period. Opiates, benzodiazepines/hypnotics (sedatives) were compared with HMG-CoA reductase inhibitors (statins), non-steroid anti-inflammatory drugs (NSAID) and beta blockers. Proton-pump inhibitors (PPI) and histamine H2-antagonists were also examined. To examine the association between above drugs and fractures the data from electronic hospital database were matched to the prescription database run by the Directorate of Health. A total of 29,056 fractures in 22,891 individuals were identified. The females with fractures were significantly older and twice as many, compared to males. The odds ratio (OR) for fractures was not significantly different between the NSAID, statins and beta blockers. OR for opiates showed almost double increased risk of fractures, 40% increased risk for sedatives and 30% increased risk for PPIs compared to beta blockers. No increased fracture-risk was noted in patients taking H2 antagonists. This study shows a relationship between the use of opiates, sedatives and bone fractures. The incidence of fractures was also increased in patients taking PPIs which is interesting in the light of the wide-spread use of PPIs in the community. Key words: Opiates, sedatives, proton- pump inhibitors, fractures. Correspondence: Magnus Johannsson, magjoh@hi.is.

All0809/8/7 is a DevBCA-like ABC-type efflux pump required for diazotrophic growth in Anabaena sp. PCC 7120.

PubMed

Staron, Peter; Maldener, Iris

2012-10-01

Efflux pumps export a wide variety of proteinaceous and non-proteinaceous substrates across the Gram-negative cell wall. For the filamentous cyanobacterium Anabaena sp. strain PCC 7120, the ATP-driven glycolipid efflux pump DevBCA-TolC has been shown to be crucial for the differentiation of N(2)-fixing heterocysts from photosynthetically active vegetative cells. In this study, a homologous system was described. All0809/8/7-TolC form a typical ATP-driven efflux pump as shown by surface plasmon resonance. This putative exporter is also involved in diazotrophic growth of Anabaena sp. PCC 7120. A mutant in all0809 encoding the periplasmic membrane fusion protein of the pump was not able to grow without combined nitrogen. Although heterocysts of this mutant were not distinguishable from those of the wild-type in light and electron micrographs, they were impaired in providing the microoxic environment necessary for N(2) fixation. RT-PCR of all0809 transcripts and localization studies on All0807-GFP revealed that All0809/8/7 was initially downregulated during heterocyst maturation and upregulated at later stages of heterocyst formation in all cells of the filament. A substrate of the efflux pump could not be identified in ATP hydrolysis assays. We discuss a role for All0809/8/7-TolC in maintaining the continuous periplasm and how this would be of special importance for heterocyst differentiation.

Experimental Observation of a Current-Driven Instability in a Neutral Electron-Positron Beam.

PubMed

Warwick, J; Dzelzainis, T; Dieckmann, M E; Schumaker, W; Doria, D; Romagnani, L; Poder, K; Cole, J M; Alejo, A; Yeung, M; Krushelnick, K; Mangles, S P D; Najmudin, Z; Reville, B; Samarin, G M; Symes, D D; Thomas, A G R; Borghesi, M; Sarri, G

2017-11-03

We report on the first experimental observation of a current-driven instability developing in a quasineutral matter-antimatter beam. Strong magnetic fields (≥1  T) are measured, via means of a proton radiography technique, after the propagation of a neutral electron-positron beam through a background electron-ion plasma. The experimentally determined equipartition parameter of ε_{B}≈10^{-3} is typical of values inferred from models of astrophysical gamma-ray bursts, in which the relativistic flows are also expected to be pair dominated. The data, supported by particle-in-cell simulations and simple analytical estimates, indicate that these magnetic fields persist in the background plasma for thousands of inverse plasma frequencies. The existence of such long-lived magnetic fields can be related to analog astrophysical systems, such as those prevalent in lepton-dominated jets.

Experimental Observation of a Current-Driven Instability in a Neutral Electron-Positron Beam

NASA Astrophysics Data System (ADS)

Warwick, J.; Dzelzainis, T.; Dieckmann, M. E.; Schumaker, W.; Doria, D.; Romagnani, L.; Poder, K.; Cole, J. M.; Alejo, A.; Yeung, M.; Krushelnick, K.; Mangles, S. P. D.; Najmudin, Z.; Reville, B.; Samarin, G. M.; Symes, D. D.; Thomas, A. G. R.; Borghesi, M.; Sarri, G.

2017-11-01

We report on the first experimental observation of a current-driven instability developing in a quasineutral matter-antimatter beam. Strong magnetic fields (≥1 T ) are measured, via means of a proton radiography technique, after the propagation of a neutral electron-positron beam through a background electron-ion plasma. The experimentally determined equipartition parameter of ɛB≈10-3 is typical of values inferred from models of astrophysical gamma-ray bursts, in which the relativistic flows are also expected to be pair dominated. The data, supported by particle-in-cell simulations and simple analytical estimates, indicate that these magnetic fields persist in the background plasma for thousands of inverse plasma frequencies. The existence of such long-lived magnetic fields can be related to analog astrophysical systems, such as those prevalent in lepton-dominated jets.

The Electron Runaround: Understanding Electric Circuit Basics through a Classroom Activity

ERIC Educational Resources Information Center

Singh, Vandana

2010-01-01

Several misconceptions abound among college students taking their first general physics course, and to some extent pre-engineering physics students, regarding the physics and applications of electric circuits. Analogies used in textbooks, such as those that liken an electric circuit to a piped closed loop of water driven by a water pump, do not…

General theory of feedback control of a nuclear spin ensemble in quantum dots

NASA Astrophysics Data System (ADS)

Yang, Wen; Sham, L. J.

2013-12-01

We present a microscopic theory of the nonequilibrium nuclear spin dynamics driven by the electron and/or hole under continuous-wave pumping in a quantum dot. We show the correlated dynamics of the nuclear spin ensemble and the electron and/or hole under optical excitation as a quantum feedback loop and investigate the dynamics of the many nuclear spins as a nonlinear collective motion. This gives rise to three observable effects: (i) hysteresis, (ii) locking (avoidance) of the pump absorption strength to (from) the natural resonance, and (iii) suppression (amplification) of the fluctuation of weakly polarized nuclear spins, leading to prolonged (shortened) electron-spin coherence time. A single nonlinear feedback function is constructed which determines the different outcomes of the three effects listed above depending on the feedback being negative or positive. The general theory also helps to put in perspective the wide range of existing theories on the problem of a single electron spin in a nuclear spin bath.

Unearthing the secrets of mitochondrial ROS and glutathione in bioenergetics.

PubMed

Mailloux, Ryan J; McBride, Skye L; Harper, Mary-Ellen

2013-12-01

During the cellular oxidation of fuels, electrons are used to power the proton pumps of the mitochondrial electron transport chain (ETC) and ultimately drive ATP synthesis and the reduction of molecular oxygen to water. During these oxidative processes, some electrons can 'spin off' during fuel oxidation and electron transport to univalently reduce O2, forming reactive oxygen species (ROS). In excess, ROS can be detrimental; however, at low concentrations oxyradicals are essential signaling molecules. Mitochondria thus use a battery of systems to finely control types and levels of ROS, including antioxidants. Several antioxidant systems depend on glutathione. Here, we review mitochondrial ROS homeostatic systems, including emerging knowledge about roles of glutathione in redox balance and the control of protein function by post-translational modification. Copyright © 2013 Elsevier Ltd. All rights reserved.

Teaching the Fundamentals of Biological Research with Primary Literature: Learning from the Discovery of the Gastric Proton Pump

ERIC Educational Resources Information Center

Zhu, Lixin

2011-01-01

For the purpose of teaching collegians the fundamentals of biological research, literature explaining the discovery of the gastric proton pump was presented in a 50-min lecture. The presentation included detailed information pertaining to the discovery process. This study was chosen because it demonstrates the importance of having a broad range of…

A thermo-physical analysis of the proton pump vacuolar-ATPase: the constructal approach.

PubMed

Lucia, Umberto; Ponzetto, Antonio; Deisboeck, Thomas S

2014-10-24

Pumping protons across a membrane was a critical step at the origin of life on earth, and it is still performed in all living organisms, including in human cells. Proton pumping is paramount to keep normal cells alive, e.g. for lysosomal digestion and for preparing peptides for immune recognition, but it goes awry in cancer cells. They acidify their microenvironment hence membrane voltage is lowered, which in turn induces cell proliferation, a hallmark of cancer. Proton pumping is achieved by means of rotary motors, namely vacuolar ATPases (V-ATPase), which are present at many of the multiple cellular interfaces. Therefore, we undertook an examination of the thermodynamic properties of V-ATPases. The principal result is that the V-ATPase-mediated control of the cell membrane potential and the related and consequent environmental pH can potentially represent a valuable support strategy for anticancer therapies. A constructal theory approach is used as a new viewpoint to study how V-ATPase can be modulated for therapeutic purposes. In particular, V-ATPase can be regulated by using external fields, such as electromagnetic fields, and a theoretical approach has been introduced to quantify the appropriate field strength and frequency for this new adjuvant therapeutic strategy.

Uncoupling and Turnover in a Cl−/H+ Exchange Transporter

PubMed Central

Walden, Michael; Accardi, Alessio; Wu, Fang; Xu, Chen; Williams, Carole; Miller, Christopher

2007-01-01

The CLC-family protein CLC-ec1, a bacterial homologue of known structure, stoichiometrically exchanges two Cl− for one H+ via an unknown membrane transport mechanism. This study examines mutations at a conserved tyrosine residue, Y445, that directly coordinates a Cl− ion located near the center of the membrane. Mutations at this position lead to “uncoupling,” such that the H+/Cl− transport ratio decreases roughly with the volume of the substituted side chain. The uncoupled proteins are still able to pump protons uphill when driven by a Cl− gradient, but the extent and rate of this H+ pumping is weaker in the more uncoupled variants. Uncoupling is accompanied by conductive Cl− transport that is not linked to counter-movement of H+, i.e., a “leak.” The unitary Cl− transport rate, measured in reconstituted liposomes by both a conventional initial-velocity method and a novel Poisson dilution approach, is ∼4,000 s−1 for wild-type protein, and the uncoupled mutants transport Cl− at similar rates. PMID:17389248

The management of gastro-oesophageal reflux disease

PubMed Central

Keung, Charlotte; Hebbard, Geoffrey

2016-01-01

SUMMARY If there are no features of serious disease, suspected gastro-oesophageal reflux disease can be initially managed with a trial of a proton pump inhibitor for 4–8 weeks. This should be taken 30–60 minutes before food for optimal effect. Once symptoms are controlled, attempt to withdraw acid suppression therapy. If symptoms recur, use the minimum dose that controls symptoms. Patients who have severe erosive oesophagitis, scleroderma oesophagus or Barrett’s oesophagus require long-term treatment with a proton pump inhibitor. Lifestyle modification strategies can help gastro-oesophageal reflux disease. Weight loss has the strongest evidence for efficacy. Further investigation and a specialist referral are required if there is no response to proton pump inhibitor therapy. Atypical symptoms or signs of serious disease also need investigation. PMID:27041798

Proton storage site in bacteriorhodopsin: new insights from QM/MM simulations of microscopic pKa and infrared spectra

PubMed Central

Goyal, Puja; Ghosh, Nilanjan; Phatak, Prasad; Clemens, Maike; Gaus, Michael; Elstner, Marcus; Cui, Qiang

2011-01-01

Identifying the group that acts as the proton storage/loading site is a challenging but important problem for understanding the mechanism of proton pumping in biomolecular proton pumps, such as bacteriorhodopsin (bR) and cytochrome c oxidase. Recent experimental studies of bR propelled the idea that the proton storage/release group (PRG) in bR is not an amino acid but a water cluster embedded in the protein. We argue that this idea is at odds with our knowledge of protein electrostatics, since invoking the water cluster as PRG would require the protein to raise the pKa of a hydronium by almost 11 pKa units, which is difficult considering known cases of pKa shifts in proteins. Our recent QM/MM simulations suggested an alternative “intermolecular proton bond” model in which the stored proton is shared between two conserved Glu residues (194 and 204). Here we show that this model leads to microscopic pKa values consistent with available experimental data and the functional requirement of a PRG. Extensive QM/MM simulations also show that, independent of a number of technical issues, such as the influence of QM region size, starting x-ray structure and nuclear quantum effects, the “intermolecular proton bond” model is qualitatively consistent with available spectroscopic data. Potential of mean force calculations show explicitly that the stored proton strongly prefers the pair of Glu residues over the water cluster. The results and analyses help highlight the importance of considering protein electrostatics and provide arguments for why the “intermolecular proton bond” model is likely applicable to PRG in biomolecular proton pumps in general. PMID:21761868

Enhanced target normal sheath acceleration of protons from intense laser interaction with a cone-tube target

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, K. D.; Huang, T. W.; Zhou, C. T., E-mail: zcangtao@iapcm.ac.cn

2016-01-15

Laser driven proton acceleration is proposed to be greatly enhanced by using a cone-tube target, which can be easily manufactured by current 3D-print technology. It is observed that energetic electron bunches are generated along the tube and accelerated to a much higher temperature by the combination of ponderomotive force and longitudinal electric field which is induced by the optical confinement of the laser field. As a result, a localized and enhanced sheath field is produced at the rear of the target and the maximum proton energy is about three-fold increased based on the two-dimentional particle-in-cell simulation results. It is demonstratedmore » that by employing this advanced target scheme, the scaling of the proton energy versus the laser intensity is much beyond the normal target normal sheath acceleration (TNSA) case.« less

Proton-Coupled Electron Transfer and a Tyrosine-Histidine Pair in a Photosystem II-Inspired β-Hairpin Maquette: Kinetics on the Picosecond Time Scale.

PubMed

Pagba, Cynthia V; McCaslin, Tyler G; Chi, San-Hui; Perry, Joseph W; Barry, Bridgette A

2016-02-25

Photosystem II (PSII) and ribonucleotide reductase employ oxidation and reduction of the tyrosine aromatic ring in radical transport pathways. Tyrosine-based reactions involve either proton-coupled electron transfer (PCET) or electron transfer (ET) alone, depending on the pH and the pKa of tyrosine's phenolic oxygen. In PSII, a subset of the PCET reactions are mediated by a tyrosine-histidine redox-driven proton relay, YD-His189. Peptide A is a PSII-inspired β-hairpin, which contains a single tyrosine (Y5) and histidine (H14). Previous electrochemical characterization indicated that Peptide A conducts a net PCET reaction between Y5 and H14, which have a cross-strand π-π interaction. The kinetic impact of H14 has not yet been explored. Here, we address this question through time-resolved absorption spectroscopy and 280-nm photolysis, which generates a neutral tyrosyl radical. The formation and decay of the neutral tyrosyl radical at 410 nm were monitored in Peptide A and its variant, Peptide C, in which H14 is replaced by cyclohexylalanine (Cha14). Significantly, both electron transfer (ET, pL 11, L = lyonium) and PCET (pL 9) were accelerated in Peptide A and C, compared to model tyrosinate or tyrosine at the same pL. Increased electronic coupling, mediated by the peptide backbone, can account for this rate acceleration. Deuterium exchange gave no significant solvent isotope effect in the peptides. At pL 9, but not at pL 11, the reaction rate decreased when H14 was mutated to Cha14. This decrease in rate is attributed to an increase in reorganization energy in the Cha14 mutant. The Y5-H14 mechanism in Peptide A is reminiscent of proton- and electron-transfer events involving YD-H189 in PSII. These results document a mechanism by which proton donors and acceptors can regulate the rate of PCET reactions.

Nonlinear optical properties of rhenium(I) complexes: Influence of the extended π-conjugated connectors and proton abstraction.

PubMed

Yu, Hai-Ling; Hong, Bo; Yang, Ning; Zhao, Hong-Yan

2015-09-01

The photoinduced proton-coupled electron transfer chemistry is very crucial to the development of nonlinear optical (NLO) materials with large first hyperpolarizability contrast. We have performed a systematic investigation on the geometric structures, NLO switching, and simulated absorption spectra of rhenium(I) complexes via density functional theory (DFT). The results show that the first hyperpolarizabilities (βvec) increase remarkably with further extending of the organic connectors. In addition, the solvent leads to a slight enhancement of the hyperpolarizability and frequency dependent hyperpolarizability. Furthermore, the proton abstraction plays an important role in tuning the second-order NLO response. It is found that deprotonation not only increases the absolute value of βvec but also changes the sign of βvec from positive to negative. This different sign can be explained by the opposite dipole moments. The efficient enhancement of first hyperpolarizability is attributed to the better delocalization of the π-electron system and the more obvious degree of charge transfer. Therefore, these kinds of complexes might be promising candidates for designed as proton driven molecular second-order NLO switching. Copyright © 2015 Elsevier Inc. All rights reserved.

Parasitic Currents Caused by Different Ionic and Electronic Conductivities in Fuel Cell Anodes.

PubMed

Schalenbach, Maximilian; Zillgitt, Marcel; Maier, Wiebke; Stolten, Detlef

2015-07-29

The electrodes in fuel cells simultaneously realize electric and ionic conductivity. In the case of acidic polymer electrolytes, the electrodes are typically made of composites of carbon-supported catalyst and Nafion polymer electrolyte binder. In this study, the interaction of the proton conduction, the electron conduction, and the electrochemical hydrogen conversion in such composite electrode materials was examined. Exposed to a hydrogen atmosphere, these composites displayed up to 10-fold smaller resistivities for the proton conduction than that of Nafion membranes. This effect was ascribed to the simultaneously occurring electrochemical hydrogen oxidation and evolution inside the composite samples, which are driven by different proton and electron resistivities. The parasitic electrochemical currents resulting were postulated to occur in the anode of fuel cells with polymer, solid oxide, or liquid alkaline electrolytes, when the ohmic drop of the ion conduction in the anode is higher with the anodic kinetic overvoltage (as illustrated in the graphical abstract). In this case, the parasitic electrochemical currents increase the anodic kinetic overpotential and the ohmic drop in the anode. Thinner fuel cell anodes with smaller ohmic drops for the ion conduction may reduce the parasitic electrochemical currents.

Gas-heat-pump development

NASA Astrophysics Data System (ADS)

Creswick, F. A.

Incentives for the development of gas heat pumps are discussed. Technical progress made on several promising technologies was reviewed. The status of development of gas-engine-driven heat pumps, the absorption cycle for the near- and long-term gas heat pump systems, the Stirling engine, the small Rankine-cycle engines, and gas-turbine-driven heat pump systems were briefly reviewed. Progress in the US, Japan, and Europe is noted.

Exchangers man the pumps: Functional interplay between proton pumps and proton-coupled Ca exchangers.

PubMed

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.

Why are patients prescribed proton pump inhibitors? Retrospective analysis of link between morbidity and prescribing in the General Practice Research Database

PubMed Central

Bashford, James N R; Norwood, Jeff; Chapman, Stephen R

1998-01-01

Objectives: To establish the relation between new prescriptions for proton pump inhibitors and recorded upper gastrointestinal morbidity within a large computerised general practitioner database. Design: Retrospective survey of morbidity and prescribing data linked to new prescriptions for proton pump inhibitors and comparison with licensed indications between 1991 and 1995. Setting: General Practice Research Database and prescribing analysis and cost (PACT) data for the former West Midlands region. Subjects: Information for 612 700 patients in the General Practice Research Database. Anonymous PACT data for all general practitioners in West Midlands region. Main outcome measures: Diagnostic codes linked to the first prescriptions issued for proton pump inhibitors; relation between new prescriptions and licensed indications; yearly change in ratio of new to repeat prescriptions and prescribing volumes measured as defined daily doses. Results: Oesophagitis was the commonest recorded indication in 1991, accounting for 31% of new prescriptions, but was third in 1995 (14%). During the study new prescriptions increased substantially, especially for duodenal disease (780%) and non-ulcer dyspepsia (690%). In 1995 non-specific morbidity accounted for 46% of new prescriptions. The total volume of prescribing rose 10-fold between 1991 and 1995, when repeat prescribing accounted for 77% of the total. Conclusions: Changes in recorded morbidity associated with new prescriptions of proton pump inhibitors did not necessarily reflect changes in licensed indications. Although general practitioners seemed to respond to changes in licensing, particularly for duodenal and gastric disease, prescribing for unlicensed indications non-ulcer dyspepsia and non-specific abdominal pain increased. Key messages There has been much speculation about the reasons behind the substantial rise in prescribing of proton pump inhibitors, especially their use for minor symptoms. We used the General Practitioner Research Database for the former West Midlands region to show that the volume of proton pump inhibitor prescribing rose 10-fold between 1992 and 1995 and repeat prescribing had risen to 77% of the volume by 1995 Prescribing for uncomplicated dyspepsia and non-specific abdominal symptoms, which were outside the licensed indications, accounted for 46% of new prescribing by 1995 The proportion of prescribing for the licensed indication of oesophagitis fell during the study, but that for duodenal ulceration increased in line with the expansion of licensed indications Analysis of PACT data showed similar prescribing trends to those found with the General Practitioner Research Database PMID:9703528

Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis.

PubMed

Alhazzani, Waleed; Alenezi, Farhan; Jaeschke, Roman Z; Moayyedi, Paul; Cook, Deborah J

2013-03-01

Critically ill patients may develop bleeding caused by stress ulceration. Acid suppression is commonly prescribed for patients at risk of stress ulcer bleeding. Whether proton pump inhibitors are more effective than histamine 2 receptor antagonists is unclear. To determine the efficacy and safety of proton pump inhibitors vs. histamine 2 receptor antagonists for the prevention of upper gastrointestinal bleeding in the ICU. We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, ACPJC, CINHAL, online trials registries (clinicaltrials.gov, ISRCTN Register, WHO ICTRP), conference proceedings databases, and reference lists of relevant articles. Randomized controlled parallel group trials comparing proton pump inhibitors to histamine 2 receptor antagonists for the prevention of upper gastrointestinal bleeding in critically ill patients, published before March 2012. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were clinically important upper gastrointestinal bleeding and overt upper gastrointestinal bleeding; secondary outcomes were nosocomial pneumonia, ICU mortality, ICU length of stay, and Clostridium difficile infection. Trial authors were contacted for additional or clarifying information. Fourteen trials enrolling a total of 1,720 patients were included. Proton pump inhibitors were more effective than histamine 2 receptor antagonists at reducing clinically important upper gastrointestinal bleeding (relative risk 0.36; 95% confidence interval 0.19-0.68; p = 0.002; I = 0%) and overt upper gastrointestinal bleeding (relative risk 0.35; 95% confidence interval 0.21-0.59; p < 0.0001; I = 15%). There were no differences between proton pump inhibitors and histamine 2 receptor antagonists in the risk of nosocomial pneumonia (relative risk 1.06; 95% confidence interval 0.73-1.52; p = 0.76; I = 0%), ICU mortality (relative risk 1.01; 95% confidence interval 0.83-1.24; p = 0.91; I = 0%), or ICU length of stay (mean difference -0.54 days; 95% confidence interval -2.20 to 1.13; p = 0.53; I = 39%). No trials reported on C. difficile infection. In critically ill patients, proton pump inhibitors seem to be more effective than histamine 2 receptor antagonists in preventing clinically important and overt upper gastrointestinal bleeding. The robustness of this conclusion is limited by the trial methodology, differences between lower and higher quality trials, sparse data, and possible publication bias. We observed no differences between drugs in the risk of pneumonia, death, or ICU length of stay.

Resonant Production of Sterile Neutrinos in the Early Universe

NASA Astrophysics Data System (ADS)

Gilbert, Lauren; Grohs, Evan; Fuller, George M.

2016-06-01

This study examines the cosmological impacts of a light resonantly produced sterile neutrino in the early universe. Such a neutrino could be produced through lepton number-driven Mikheyev-Smirnov-Wolfenstein (MSW) conversion of active neutrinos around big bang nucleosynthesis (BBN), resulting in a non-thermal spectrum of both sterile and electron neutrinos. During BBN, the neutron-proton ratio depends sensitively on the electron neutrino flux. If electron neutrinos are being converted to sterile neutrinos, this makes the n/p ratio a probe of possible new physics. We use observations of primordial Yp and D/H to place limits on this process.

The controlled relay of multiple protons required at the active site of nitrogenase.

PubMed

Dance, Ian

2012-07-07

The enzyme nitrogenase, when reducing natural and unnatural substrates, requires large numbers of protons per chemical catalytic cycle. The active face of the catalytic site (the FeMo-cofactor, FeMo-co) is situated in a protein domain which is largely hydrophobic and anhydrous, and incapable of serial provision of multiple protons. Through detailed analysis of the high quality protein crystal structures available the characteristics of a chain of water molecules leading from the protein surface to a key sulfur atom (S3B) of FeMo-co are described. The first half of the water chain from the surface inwards is branched, slightly variable, and able to accommodate exogenous small molecules: this is dubbed the proton bay. The second half, from the proton bay to S3B, is comprised of a single chain of eight hydrogen bonded water molecules. This section is strictly conserved, and is intimately involved in hydrogen bonds with homocitrate, an essential component that chelates Mo. This is the proton wire, and a detailed Grotthuss mechanism for serial translocation of protons through this proton wire to S3B is proposed. This controlled serial proton relay from the protein surface to S3B is an essential component of the intramolecular hydrogenation paradigm for the complete chemical mechanisms of nitrogenase. Each proton reaching S3B, instigated by electron transfer to FeMo-co, becomes a hydrogen atom that migrates to other components of the active face of FeMo-co and to bound substrates and intermediates, allowing subsequent multiple proton transfers along the proton wire. Experiments to test the proposed mechanism of proton supply are suggested. The water chain in nitrogenase is comparable with the purported proton pumping pathway of cytochrome c oxidase.

An online, energy-resolving beam profile detector for laser-driven proton beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Metzkes, J.; Rehwald, M.; Obst, L.

In this paper, a scintillator-based online beam profile detector for the characterization of laser-driven proton beams is presented. Using a pixelated matrix with varying absorber thicknesses, the proton beam is spatially resolved in two dimensions and simultaneously energy-resolved. A thin plastic scintillator placed behind the absorber and read out by a CCD camera is used as the active detector material. The spatial detector resolution reaches down to ∼4 mm and the detector can resolve proton beam profiles for up to 9 proton threshold energies. With these detector design parameters, the spatial characteristics of the proton distribution and its cut-off energymore » can be analyzed online and on-shot under vacuum conditions. The paper discusses the detector design, its characterization and calibration at a conventional proton source, as well as the first detector application at a laser-driven proton source.« less

An online, energy-resolving beam profile detector for laser-driven proton beams.

PubMed

Metzkes, J; Zeil, K; Kraft, S D; Karsch, L; Sobiella, M; Rehwald, M; Obst, L; Schlenvoigt, H-P; Schramm, U

2016-08-01

In this paper, a scintillator-based online beam profile detector for the characterization of laser-driven proton beams is presented. Using a pixelated matrix with varying absorber thicknesses, the proton beam is spatially resolved in two dimensions and simultaneously energy-resolved. A thin plastic scintillator placed behind the absorber and read out by a CCD camera is used as the active detector material. The spatial detector resolution reaches down to ∼4 mm and the detector can resolve proton beam profiles for up to 9 proton threshold energies. With these detector design parameters, the spatial characteristics of the proton distribution and its cut-off energy can be analyzed online and on-shot under vacuum conditions. The paper discusses the detector design, its characterization and calibration at a conventional proton source, as well as the first detector application at a laser-driven proton source.

New approaches in clinical application of laser-driven ionizing radiation

NASA Astrophysics Data System (ADS)

Hideghéty, Katalin; Szabó, Rita Emilia; Polanek, Róbert; Szabó, Zoltán.; Brunner, Szilvia; Tőkés, Tünde

2017-05-01

The planned laser-driven ionizing beams (photon, very high energy electron, proton, carbon ion) at laser facilities have the unique property of ultra-high dose rate (>Gy/s-10), short pulses, and at ELI-ALPS high repetition rate, carry the potential to develop novel laser-driven methods towards compact hospital-based clinical application. The enhanced flexibility in particle and energy selection, the high spatial and time resolution and extreme dose rate could be highly beneficial in radiotherapy. These approaches may increase significantly the therapeutic index over the currently available advanced radiation oncology methods. We highlight two nuclear reactionbased binary modalities and the planned radiobiology research. Boron Neutron Capture Therapy is an advanced cell targeted modality requiring 10B enriched boron carrier and appropriate neutron beam. The development of laser-based thermal and epithermal neutron source with as high as 1010 fluence rate could enhance the research activity in this promising field. Boron-Proton Fusion reaction is as well as a binary approach, where 11B containing compounds are accumulated into the cells, and the tumour selectively irradiated with protons. Due to additional high linear energy transfer alpha particle release of the BPFR and the maximum point of the Bragg-peak is increased, which result in significant biological effect enhancement. Research at ELI-ALPS on detection of biological effect differences of modified or different quality radiation will be presented using recently developed zebrafish embryo and rodent models.

Fabrication and characterization of microcavity lasers in rhodamine B doped SU8 using high energy proton beam

NASA Astrophysics Data System (ADS)

Venugopal Rao, S.; Bettiol, A. A.; Vishnubhatla, K. C.; Bhaktha, S. N. B.; Narayana Rao, D.; Watt, F.

2007-03-01

The authors present their results on the characterization of individual dye-doped microcavity polymer lasers fabricated using a high energy proton beam. The lasers were fabricated in rhodamine B doped SU8 resist with a single exposure step followed by chemical processing. The resulting trapezoidal shaped cavities had dimensions of ˜250×250μm2. Physical characterization of these structures was performed using a scanning electron microscope while the optical characterization was carried out by recording the emission subsequent to pumping the lasers with 532nm, 6 nanosecond pulses. The authors observed intense, narrow emission near 624nm with the best emission linewidth full width at half maximum of ˜9nm and a threshold ˜150μJ/mm2.

Performance of irradiated CVD diamond micro-strip sensors

NASA Astrophysics Data System (ADS)

Adam, W.; Berdermann, E.; Bergonzo, P.; Bertuccio, G.; Bogani, F.; Borchi, E.; Brambilla, A.; Bruzzi, M.; Colledani, C.; Conway, J.; D'Angelo, P.; Dabrowski, W.; Delpierre, P.; Deneuville, A.; Dulinski, W.; van Eijk, B.; Fallou, A.; Fizzotti, F.; Foulon, F.; Friedl, M.; Gan, K. K.; Gheeraert, E.; Hallewell, G.; Han, S.; Hartjes, F.; Hrubec, J.; Husson, D.; Kagan, H.; Kania, D.; Kaplon, J.; Kass, R.; Koeth, T.; Krammer, M.; Logiudice, A.; Lu, R.; mac Lynne, L.; Manfredotti, C.; Meier, D.; Mishina, M.; Moroni, L.; Noomen, J.; Oh, A.; Pan, L. S.; Pernicka, M.; Peitz, A.; Perera, L.; Pirollo, S.; Procario, M.; Riester, J. L.; Roe, S.; Rousseau, L.; Rudge, A.; Russ, J.; Sala, S.; Sampietro, M.; Schnetzer, S.; Sciortino, S.; Stelzer, H.; Stone, R.; Suter, B.; Tapper, R. J.; Tesarek, R.; Trischuk, W.; Tromson, D.; Vittone, E.; Walsh, A. M.; Wedenig, R.; Weilhammer, P.; Wetstein, M.; White, C.; Zeuner, W.; Zoeller, M.; Plano, R.; Somalwar, S. V.; Thomson, G. B.

2002-01-01

CVD diamond detectors are of interest for charged particle detection and tracking due to their high radiation tolerance. In this article, we present, for the first time, beam test results from recently manufactured CVD diamond strip detectors and their behavior under low doses of electrons from a β-source and the performance before and after intense (>10 15/cm 2) proton- and pion-irradiations. We find that low dose irradiation increase the signal-to-noise ratio (pumping of the signal) and slightly deteriorate the spatial resolution. Intense irradiation with protons 2.2×10 15 p/ cm2 lowers the signal-to-noise ratio slightly. Intense irradiation with pions 2.9×10 15 π/ cm2 lowers the signal-to-noise ratio more. The spatial resolution of the diamond sensors improves after irradiations.

Experimental Observation of a Current-Driven Instability in a Neutral Electron-Positron Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warwick, J.; Dzelzainis, T.; Dieckmann, M. E.

Here, we report on the first experimental observation of a current-driven instability developing in a quasineutral matter-antimatter beam. Strong magnetic fields (≥ 1T) are measured, via means of a proton radiography technique, after the propagation of a neutral electron-positron beam through a background electron-ion plasma. The experimentally determined equipartition parameter of ε B ≈ 10 -3 is typical of values inferred from models of astrophysical gamma-ray bursts, in which the relativistic flows are also expected to be pair dominated. The data, supported by particle-in-cell simulations and simple analytical estimates, indicate that these magnetic fields persist in the background plasma formore » thousands of inverse plasma frequencies. The existence of such long-lived magnetic fields can be related to analog astrophysical systems, such as those prevalent in lepton-dominated jets.« less

Experimental Observation of a Current-Driven Instability in a Neutral Electron-Positron Beam

DOE PAGES

Warwick, J.; Dzelzainis, T.; Dieckmann, M. E.; ...

2017-11-03

Here, we report on the first experimental observation of a current-driven instability developing in a quasineutral matter-antimatter beam. Strong magnetic fields (≥ 1T) are measured, via means of a proton radiography technique, after the propagation of a neutral electron-positron beam through a background electron-ion plasma. The experimentally determined equipartition parameter of ε B ≈ 10 -3 is typical of values inferred from models of astrophysical gamma-ray bursts, in which the relativistic flows are also expected to be pair dominated. The data, supported by particle-in-cell simulations and simple analytical estimates, indicate that these magnetic fields persist in the background plasma formore » thousands of inverse plasma frequencies. The existence of such long-lived magnetic fields can be related to analog astrophysical systems, such as those prevalent in lepton-dominated jets.« less

Electro-opto-mechanical radio-frequency oscillator driven by guided acoustic waves in standard single-mode fiber

NASA Astrophysics Data System (ADS)

London, Yosef; Diamandi, Hilel Hagai; Zadok, Avi

2017-04-01

An opto-electronic radio-frequency oscillator that is based on forward scattering by the guided acoustic modes of a standard single-mode optical fiber is proposed and demonstrated. An optical pump wave is used to stimulate narrowband, resonant guided acoustic modes, which introduce phase modulation to a co-propagating optical probe wave. The phase modulation is converted to an intensity signal at the output of a Sagnac interferometer loop. The intensity waveform is detected, amplified, and driven back to modulate the optical pump. Oscillations are achieved at a frequency of 319 MHz, which matches the resonance of the acoustic mode that provides the largest phase modulation of the probe wave. Oscillations at the frequencies of competing acoustic modes are suppressed by at least 40 dB. The linewidth of the acoustic resonance is sufficiently narrow to provide oscillations at a single longitudinal mode of the hybrid cavity. Competing longitudinal modes are suppressed by at least 38 dB as well. Unlike other opto-electronic oscillators, no radio-frequency filtering is required within the hybrid cavity. The frequency of oscillations is entirely determined by the fiber opto-mechanics.

Mechanism of Nitrogenase H 2 Formation by Metal-Hydride Protonation Probed by Mediated Electrocatalysis and H/D Isotope Effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khadka, Nimesh; Milton, Ross D.; Shaw, Sudipta

Nitrogenase catalyzes the reduction of dinitrogen (N2) to ammonia (NH3) with obligatory reduction of protons (H+) to dihydrogen (H2) through a mechanism involving reductive elimination of two [Fe-H-Fe] bridging hydrides at its active site FeMo-cofactor. The overall rate-limiting step is associated with ATP-driven electron delivery from Fe protein, precluding isotope effect measurements on substrate reduction steps. Here, we use mediated bioelectrocatalysis to drive electron delivery to MoFe protein without Fe protein and ATP hydrolysis, thereby eliminating the normal rate-limiting step. The ratio of catalytic current in mixtures of H2O and D2O, the proton inventory, changes linearly with the D2O/H2O ratio,more » revealing that a single H/D is involved in the rate limiting step. Kinetic models, along with measurements that vary the electron/proton delivery rate and use different substrates, reveal that the rate-limiting step under these conditions is the H2 formation reaction. Altering the chemical environment around the active site FeMo-cofactor in the MoFe protein either by substituting nearby amino acids or transferring the isolated FeMo-cofactor into a different peptide matrix, changes the net isotope effect, but the proton inventory plot remains linear, consistent with an unchanging rate-limiting step. Density functional theory predicts a transition state for H2 formation where the proton from S-H+ moves to the hydride in Fe-H-, predicting the number and magnitude of the observed H/D isotope effect. This study not only reveals the mechanism of H2 formation, but also illustrates a strategy for mechanistic study that can be applied to other enzymes and to biomimetic complexes.« less

Ponderomotive electron acceleration in a silicon-based nanoplasmonic waveguide.

PubMed

Sederberg, S; Elezzabi, A Y

2014-10-17

Ponderomotive electron acceleration is demonstrated in a semiconductor-loaded nanoplasmonic waveguide. Photogenerated free carriers are accelerated by the tightly confined nanoplasmonic fields and reach energies exceeding the threshold for impact ionization. Broadband (375 nm ≤ λ ≤ 650  nm) white light emission is observed from the nanoplasmonic waveguides. Exponential growth of visible light emission confirms the exponential growth of the electron population, demonstrating the presence of an optical-field-driven electron avalanche. Electron sweeping dynamics are visualized using pump-probe measurements, and a sweeping time of 1.98 ± 0.40 ps is measured. These findings offer a means to harness the potential of the emerging field of ultrafast nonlinear nanoplasmonics.

Protein Activity of the Fusarium fujikuroi Rhodopsins CarO and OpsA and Their Relation to Fungus–Plant Interaction

PubMed Central

Adam, Alexander; Deimel, Stephan; Pardo-Medina, Javier; García-Martínez, Jorge; Konte, Tilen; Limón, M. Carmen; Avalos, Javier

2018-01-01

Fungi possess diverse photosensory proteins that allow them to perceive different light wavelengths and to adapt to changing light conditions in their environment. The biological and physiological roles of the green light-sensing rhodopsins in fungi are not yet resolved. The rice plant pathogen Fusarium fujikuroi exhibits two different rhodopsins, CarO and OpsA. CarO was previously characterized as a light-driven proton pump. We further analyzed the pumping behavior of CarO by patch-clamp experiments. Our data show that CarO pumping activity is strongly augmented in the presence of the plant hormone indole-3-acetic acid and in sodium acetate, in a dose-dependent manner under slightly acidic conditions. By contrast, under these and other tested conditions, the Neurospora rhodopsin (NR)-like rhodopsin OpsA did not exhibit any pump activity. Basic local alignment search tool (BLAST) searches in the genomes of ascomycetes revealed the occurrence of rhodopsin-encoding genes mainly in phyto-associated or phytopathogenic fungi, suggesting a possible correlation of the presence of rhodopsins with fungal ecology. In accordance, rice plants infected with a CarO-deficient F. fujikuroi strain showed more severe bakanae symptoms than the reference strain, indicating a potential role of the CarO rhodopsin in the regulation of plant infection by this fungus. PMID:29324661

A new hypothesis on the simultaneous direct and indirect proton pump mechanisms in NADH-quinone oxidoreductase (complex I)

PubMed Central

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

2010-01-01

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−. PMID:20816962

[Proton pump inhibitor - side effects and complications of long-term proton pump inhibitor administration].

PubMed

Ueberschaer, Hendrik; Allescher, Hans-Dieter

2017-01-01

Proton Pump Inhibitors are among the most common drugs taken. The indication is for treatment of heartburn, reflux disease, prophylaxis and treatment of peptic ulcers, in combination with NSAIDs and steroids as well as H. pylori-eradication. PPI's are widely used, even with non-specific symptoms. This certainly has to do with good tolerability and a previously considered low side effect profile. At the moment, there is growing evidence that the long-term intake of PPI's may not be as safe as assumed. In addition to interactions with some drugs, including platelet aggregation inhibitors, recent studies have shown an increased risk of myocardial infarction, interstitial nephritis, chronic renal injury, infections, vitamin deficiencies and electrolyte shifts as well developing dementia. © Georg Thieme Verlag KG Stuttgart · New York.

Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan.

PubMed

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).

Proton Pump Inhibition Increases Rapid Eye Movement Sleep in the Rat

PubMed Central

Jha, Sushil K.

2014-01-01

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. PMID:24701564

A magnetically driven piston pump for ultra-clean applications

NASA Astrophysics Data System (ADS)

LePort, F.; Neilson, R.; Barbeau, P. S.; Barry, K.; Bartoszek, L.; Counts, I.; Davis, J.; deVoe, R.; Dolinski, M. J.; Gratta, G.; Green, M.; Díez, M. Montero; Müller, A. R.; O'Sullivan, K.; Rivas, A.; Twelker, K.; Aharmim, B.; Auger, M.; Belov, V.; Benitez-Medina, C.; Breidenbach, M.; Burenkov, A.; Cleveland, B.; Conley, R.; Cook, J.; Cook, S.; Craddock, W.; Daniels, T.; Dixit, M.; Dobi, A.; Donato, K.; Fairbank, W.; Farine, J.; Fierlinger, P.; Franco, D.; Giroux, G.; Gornea, R.; Graham, K.; Green, C.; Hägemann, C.; Hall, C.; Hall, K.; Hallman, D.; Hargrove, C.; Herrin, S.; Hughes, M.; Hodgson, J.; Juget, F.; Kaufman, L. J.; Karelin, A.; Ku, J.; Kuchenkov, A.; Kumar, K.; Leonard, D. S.; Lutter, G.; Mackay, D.; MacLellan, R.; Marino, M.; Mong, B.; Morgan, P.; Odian, A.; Piepke, A.; Pocar, A.; Prescott, C. Y.; Pushkin, K.; Rollin, E.; Rowson, P. C.; Schmoll, B.; Sinclair, D.; Skarpaas, K.; Slutsky, S.; Stekhanov, V.; Strickland, V.; Swift, M.; Vuilleumier, J.-L.; Vuilleumier, J.-M.; Wichoski, U.; Wodin, J.; Yang, L.; Yen, Y.-R.

2011-10-01

A magnetically driven piston pump for xenon gas recirculation is presented. The pump is designed to satisfy extreme purity and containment requirements, as is appropriate for the recirculation of isotopically enriched xenon through the purification system and large liquid xenon time projection chamber of EXO-200. The pump, using sprung polymer gaskets, is capable of pumping more than 16 standard liters per minute of xenon gas with 750 Torr differential pressure.

A magnetically driven piston pump for ultra-clean applications.

PubMed

LePort, F; Neilson, R; Barbeau, P S; Barry, K; Bartoszek, L; Counts, I; Davis, J; deVoe, R; Dolinski, M J; Gratta, G; Green, M; Montero Díez, M; Müller, A R; O'Sullivan, K; Rivas, A; Twelker, K; Aharmim, B; Auger, M; Belov, V; Benitez-Medina, C; Breidenbach, M; Burenkov, A; Cleveland, B; Conley, R; Cook, J; Cook, S; Craddock, W; Daniels, T; Dixit, M; Dobi, A; Donato, K; Fairbank, W; Farine, J; Fierlinger, P; Franco, D; Giroux, G; Gornea, R; Graham, K; Green, C; Hägemann, C; Hall, C; Hall, K; Hallman, D; Hargrove, C; Herrin, S; Hughes, M; Hodgson, J; Juget, F; Kaufman, L J; Karelin, A; Ku, J; Kuchenkov, A; Kumar, K; Leonard, D S; Lutter, G; Mackay, D; MacLellan, R; Marino, M; Mong, B; Morgan, P; Odian, A; Piepke, A; Pocar, A; Prescott, C Y; Pushkin, K; Rollin, E; Rowson, P C; Schmoll, B; Sinclair, D; Skarpaas, K; Slutsky, S; Stekhanov, V; Strickland, V; Swift, M; Vuilleumier, J-L; Vuilleumier, J-M; Wichoski, U; Wodin, J; Yang, L; Yen, Y-R

2011-10-01

A magnetically driven piston pump for xenon gas recirculation is presented. The pump is designed to satisfy extreme purity and containment requirements, as is appropriate for the recirculation of isotopically enriched xenon through the purification system and large liquid xenon time projection chamber of EXO-200. The pump, using sprung polymer gaskets, is capable of pumping more than 16 standard liters per minute of xenon gas with 750 Torr differential pressure.

F1 rotary motor of ATP synthase is driven by the torsionally-asymmetric drive shaft

PubMed Central

Kulish, O.; Wright, A. D.; Terentjev, E. M.

2016-01-01

F1F0 ATP synthase (ATPase) either facilitates the synthesis of ATP in a process driven by the proton moving force (pmf), or uses the energy from ATP hydrolysis to pump protons against the concentration gradient across the membrane. ATPase is composed of two rotary motors, F0 and F1, which compete for control of their shared γ -shaft. We present a self-consistent physical model of F1 motor as a simplified two-state Brownian ratchet using the asymmetry of torsional elastic energy of the coiled-coil γ -shaft. This stochastic model unifies the physical concepts of linear and rotary motors, and explains the stepped unidirectional rotary motion. Substituting the model parameters, all independently known from recent experiments, our model quantitatively reproduces the ATPase operation, e.g. the ‘no-load’ angular velocity is ca. 400 rad/s anticlockwise at 4 mM ATP. Increasing the pmf torque exerted by F0 can slow, stop and overcome the torque generated by F1, switching from ATP hydrolysis to synthesis at a very low value of ‘stall torque’. We discuss the motor efficiency, which is very low if calculated from the useful mechanical work it produces - but is quite high when the ‘useful outcome’ is measured in the number of H+ pushed against the chemical gradient. PMID:27321713

Halorhodopsin pumps Cl– and bacteriorhodopsin pumps protons by a common mechanism that uses conserved electrostatic interactions

PubMed Central

Gunner, M. R.

2014-01-01

Key mutations differentiate the functions of homologous proteins. One example compares the inward ion pump halorhodopsin (HR) and the outward proton pump bacteriorhodopsin (BR). Of the nine essential buried ionizable residues in BR, six are conserved in HR. However, HR changes three BR acids, D85 in a central cluster of ionizable residues, D96, nearer the intracellular, and E204, nearer the extracellular side of the membrane to the small, neutral amino acids T111, V122, and T230, respectively. In BR, acidic amino acids are stationary anions whose proton affinity is modulated by conformational changes, establishing a sequence of directed binding and release of protons. Multiconformation continuum electrostatics calculations of chloride affinity and residue protonation show that, in reaction intermediates where an acid is ionized in BR, a Cl– is bound to HR in a position near the deleted acid. In the HR ground state, Cl– binds tightly to the central cluster T111 site and weakly to the extracellular T230 site, recovering the charges on ionized BR-D85 and neutral E204 in BR. Imposing key conformational changes from the BR M intermediate into the HR structure results in the loss of Cl– from the central T111 site and the tight binding of Cl– to the extracellular T230 site, mirroring the changes that protonate BR-D85 and ionize E204 in BR. The use of a mobile chloride in place of D85 and E204 makes HR more susceptible to the environmental pH and salt concentrations than BR. These studies shed light on how ion transfer mechanisms are controlled through the interplay of protein and ion electrostatics. PMID:25362051

Accelerator driven sub-critical core

DOEpatents

McIntyre, Peter M; Sattarov, Akhdiyor

2015-03-17

Systems and methods for operating an accelerator driven sub-critical core. In one embodiment, a fission power generator includes a sub-critical core and a plurality of proton beam generators. Each of the proton beam generators is configured to concurrently provide a proton beam into a different area of the sub-critical core. Each proton beam scatters neutrons within the sub-critical core. The plurality of proton beam generators provides aggregate power to the sub-critical core, via the proton beams, to scatter neutrons sufficient to initiate fission in the sub-critical core.

Nuclear-Pumped Lasers. [efficient conversion of energy liberated in nuclear reactions to coherent radiation

NASA Technical Reports Server (NTRS)

1979-01-01

The state of the art in nuclear pumped lasers is reviewed. Nuclear pumped laser modeling, nuclear volume and foil excitation of laser plasmas, proton beam simulations, nuclear flashlamp excitation, and reactor laser systems studies are covered.

Interplay between protons and electrons in a firehose-unstable plasma: Particle-in-cell simulations

NASA Astrophysics Data System (ADS)

Bourdin, Philippe-A.; Maneva, Yana

2017-04-01

Kinetic plasma instabilities originating from unstable, non-Maxwellian shapes of the velocity distribution functions serve as internal degrees of freedom in plasma dynamics, and play an important role near solar current sheets and in solar wind plasmas. In the presence of strong temperature anisotropy (different thermal spreads in the velocity space with respect to the mean magnetic field), plasmas are unstable either to the firehose mode or to the mirror mode in the case of predominant parallel and perpendicular temperatures, respectively. The growth rates of these instabilities and their thresholds depend on plasma properties, such as the temperature anisotropy and the plasma beta. The physics of the temperature anisotropy-driven instabilities becomes even more diverse for various shapes of velocity distribution functions and the particle species of interest. Recent studies based on a linear instability analysis show an interplay in the firehose instability between protons and electrons when the both types of particle species are prone to unstable velocity distribution functions and their instability thresholds. In this work we perform for the first time 3D nonlinear PIC (particle-in-cell) numerical simulations to test for the linear-theory prediction of the simultaneous proton-electron firehose instability. The simulation setup allows us not only to evaluate the growth rate of each firehose instability, but also to track its nonlinear evolution and the related wave-particle interactions such as the pitch-angle scattering or saturation effects. The specialty of our simulation is that the magnetic and electric fields have a low numerical noise level by setting a sufficiently large number of super-particles into the simulation box and enhancing the statistical significance of the velocity distribution functions. We use the iPIC3D code with fully periodic boundaries under various conditions of the electron-to-proton mass ratio, which gives insight into the instability interplay at the intermediate electron-proton and on the scaling of our results towards more realistic particle settings.

Solar Powered CO.Sub.2 Conversion

NASA Technical Reports Server (NTRS)

Chen, Bin (Inventor)

2016-01-01

Methods and devices for reducing CO.sub.2 to produce hydrocarbons are disclosed. A device comprises a photoanode capable of splitting H.sub.2O into electrons, protons, and oxygen; an electrochemical cell cathode comprising an electro-catalyst capable of reducing CO.sub.2; H.sub.2O in contact with the surface of the photoanode; CO.sub.2 in contact with the surface of the cathode; and a proton-conducting medium positioned between the photoanode and the cathode. Electrical charges associated with the protons and the electrons move from the photoanode to the cathode, driven in part by a chemical potential difference sufficient to drive the electrochemical reduction of CO.sub.2 at the cathode. A light beam is the sole source of energy used to drive chemical reactions. The photoanode can comprise TiO.sub.2 nanowires or nanotubes, and can also include WO.sub.3 nanowires or nanotubes, quantum dots of CdS or PbS, and Ag or Au nanostructures. The cathode can comprise a conductive gas diffusion layer with nanostructures of an electro-catalyst such as Cu or Co.

The use of nanomaterials for mass spectrometry can be uplifting for analyte detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, J.; Lipson, R. H.

2014-03-31

Surface-Assisted Laser Desorption Ionization (SALDI) involves desorbing and ionizing analyte molecules from a nanoporous substrate by laser irradiation for detection in a mass spectrometer. In this work experiments were designed to better understand the mechanisms governing desorption and ionization for Desorption Ionization On Silicon (DIOS), a variant of SALDI which uses porous silicon (pSi) as a substrate. Experiments are also reported for other nanoporous semiconducting materials (WO{sub 3}, TiO{sub 2}) which exhibit very similar behaviors; specifically, that both protonated analyte ions and analyte radical cations can be generated with relative intensities that depend on the position of the incident lasermore » focus relative to substrate surface. While thermal desorption appears to be important, preliminary evidence suggests that the ionization mechanism leading to protonated analytes involves in part electrons and holes formed when photoexciting the substrate above its electronic band gap, and the presence of defect states within the band gap. Radical cation formation appears to be driven in part by electron transfer due to the large electron affinity of each substrate used in this work.« less

Generic picture of the emission properties of III-nitride polariton laser diodes: Steady state and current modulation response

NASA Astrophysics Data System (ADS)

Iorsh, Ivan; Glauser, Marlene; Rossbach, Georg; Levrat, Jacques; Cobet, Munise; Butté, Raphaël; Grandjean, Nicolas; Kaliteevski, Mikhail A.; Abram, Richard A.; Kavokin, Alexey V.

2012-09-01

The main emission characteristics of electrically driven polariton lasers based on planar GaN microcavities with embedded InGaN quantum wells are studied theoretically. The polariton emission dependence on pump current density is first modeled using a set of semiclassical Boltzmann equations for the exciton polaritons that are coupled to the rate equation describing the electron-hole plasma population. Two experimentally relevant pumping geometries are considered, namely the direct injection of electrons and holes into the strongly coupled microcavity region and intracavity optical pumping via an embedded light-emitting diode. The theoretical framework allows the determination of the minimum threshold current density Jthr,min as a function of lattice temperature and exciton-cavity photon detuning for the two pumping schemes. A Jthr,min value of 5 and 6 A cm-2 is derived for the direct injection scheme and for the intracavity optical pumping one, respectively, at room temperature at the optimum detuning. Then an approximate quasianalytical model is introduced to derive solutions for both the steady-state and high-speed current modulation. This analysis makes it possible to show that the exciton population, which acts as a reservoir for the stimulated relaxation process, gets clamped once the condensation threshold is crossed, a behavior analogous to what happens in conventional laser diodes with the carrier density above threshold. Finally, the modulation transfer function is calculated for both pumping geometries and the corresponding cutoff frequency is determined.

A Conserved Asparagine in a P-type Proton Pump Is Required for Efficient Gating of Protons*

PubMed Central

Ekberg, Kira; Wielandt, Alex G.; Buch-Pedersen, Morten J.; Palmgren, Michael G.

2013-01-01

The minimal proton pumping machinery of the Arabidopsis thaliana P-type plasma membrane H+-ATPase isoform 2 (AHA2) consists of an aspartate residue serving as key proton donor/acceptor (Asp-684) and an arginine residue controlling the pKa of the aspartate. However, other important aspects of the proton transport mechanism such as gating, and the ability to occlude protons, are still unclear. An asparagine residue (Asn-106) in transmembrane segment 2 of AHA2 is conserved in all P-type plasma membrane H+-ATPases. In the crystal structure of the plant plasma membrane H+-ATPase, this residue is located in the putative ligand entrance pathway, in close proximity to the central proton donor/acceptor Asp-684. Substitution of Asn-106 resulted in mutant enzymes with significantly reduced ability to transport protons against a membrane potential. Sensitivity toward orthovanadate was increased when Asn-106 was substituted with an aspartate residue, but decreased in mutants with alanine, lysine, glutamine, or threonine replacement of Asn-106. The apparent proton affinity was decreased for all mutants, most likely due to a perturbation of the local environment of Asp-684. Altogether, our results demonstrate that Asn-106 is important for closure of the proton entrance pathway prior to proton translocation across the membrane. PMID:23420846

A conserved asparagine in a P-type proton pump is required for efficient gating of protons.

PubMed

Ekberg, Kira; Wielandt, Alex G; Buch-Pedersen, Morten J; Palmgren, Michael G

2013-04-05

The minimal proton pumping machinery of the Arabidopsis thaliana P-type plasma membrane H(+)-ATPase isoform 2 (AHA2) consists of an aspartate residue serving as key proton donor/acceptor (Asp-684) and an arginine residue controlling the pKa of the aspartate. However, other important aspects of the proton transport mechanism such as gating, and the ability to occlude protons, are still unclear. An asparagine residue (Asn-106) in transmembrane segment 2 of AHA2 is conserved in all P-type plasma membrane H(+)-ATPases. In the crystal structure of the plant plasma membrane H(+)-ATPase, this residue is located in the putative ligand entrance pathway, in close proximity to the central proton donor/acceptor Asp-684. Substitution of Asn-106 resulted in mutant enzymes with significantly reduced ability to transport protons against a membrane potential. Sensitivity toward orthovanadate was increased when Asn-106 was substituted with an aspartate residue, but decreased in mutants with alanine, lysine, glutamine, or threonine replacement of Asn-106. The apparent proton affinity was decreased for all mutants, most likely due to a perturbation of the local environment of Asp-684. Altogether, our results demonstrate that Asn-106 is important for closure of the proton entrance pathway prior to proton translocation across the membrane.

Squeezing at Entrance of Proton Transport Pathway in Proton-translocating Pyrophosphatase upon Substrate Binding*

PubMed Central

Huang, Yun-Tzu; Liu, Tseng-Huang; Lin, Shih-Ming; Chen, Yen-Wei; Pan, Yih-Jiuan; Lee, Ching-Hung; Sun, Yuh-Ju; Tseng, Fan-Gang; Pan, Rong-Long

2013-01-01

Homodimeric proton-translocating pyrophosphatase (H+-PPase; EC 3.6.1.1) is indispensable for many organisms in maintaining organellar pH homeostasis. This unique proton pump couples the hydrolysis of PPi to proton translocation across the membrane. H+-PPase consists of 14–16 relatively hydrophobic transmembrane domains presumably for proton translocation and hydrophilic loops primarily embedding a catalytic site. Several highly conserved polar residues located at or near the entrance of the transport pathway in H+-PPase are essential for proton pumping activity. In this investigation single molecule FRET was employed to dissect the action at the pathway entrance in homodimeric Clostridium tetani H+-PPase upon ligand binding. The presence of the substrate analog, imidodiphosphate mediated two sites at the pathway entrance moving toward each other. Moreover, single molecule FRET analyses after the mutation at the first proton-carrying residue (Arg-169) demonstrated that conformational changes at the entrance are conceivably essential for the initial step of H+-PPase proton translocation. A working model is accordingly proposed to illustrate the squeeze at the entrance of the transport pathway in H+-PPase upon substrate binding. PMID:23720778

Numerical study of bandwidth effect on stimulated Raman backscattering in nonlinear regime

NASA Astrophysics Data System (ADS)

Zhou, H. Y.; Xiao, C. Z.; Zou, D. B.; Li, X. Z.; Yin, Y.; Shao, F. Q.; Zhuo, H. B.

2018-06-01

Nonlinear behaviors of stimulated Raman scattering driven by finite bandwidth pumps are studied by one dimensional particle-in-cell simulations. The broad spectral feature of plasma waves and backscattered light reveals the different coupling and growth mechanisms, which lead to the suppression effect before the deep nonlinear stage. It causes nonperiodic plasma wave packets and reduces packet and etching velocities. Based on the negative frequency shift and electron energy distribution, the long-time evolution of instability can be divided into two stages by the relaxation time. It is a critical time after which the alleviation effects of nonlinear frequency shift and hot electrons are replaced by enhancement. Thus, the broadband pump suppresses instability at early time. However, it aggravates in the deep nonlinear stage by lifting the saturation level due to the coupling of the incident pump with each frequency shifted plasma wave. Our simulation results show that the nonlinear effects are valid in a bandwidth range from 2.25% to 3.0%, and the physics are similar within a nearby parameter space.

A rationale for the use of proton pump inhibitors as antineoplastic agents.

PubMed

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.

A new hypothesis on the simultaneous direct and indirect proton pump mechanisms in NADH-quinone oxidoreductase (complex I).

PubMed

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.

Fatal spontaneous Clostridium septicum gas gangrene: a possible association with iatrogenic gastric acid suppression.

PubMed

Wu, Yiru E; Baras, Alexander; Cornish, Toby; Riedel, Stefan; Burton, Elizabeth C

2014-06-01

The long-term use of proton pump inhibitors has been linked to an increased risk for the development of gastric polyps, hip fractures, pneumonia, and Clostridium difficile colitis. There is evidence that chronic acid suppression from long-term use of proton pump inhibitors poses some risk for the development of C difficile-associated diarrhea by decreasing the elimination of pathogenic microbes before reaching the lower gastrointestinal tract. Here we present a case of a 51-year-old woman with a recent history of abdominal pain and fever who presented to the emergency department with rapidly progressive spontaneous necrotizing fasciitis and gas gangrene and died within hours of presentation. Postmortem examination confirmed spreading tissue gas gangrene and myonecrosis. In addition, multiple intestinal ulcers containing Clostridium septicum were present at autopsy. This case illustrates a possible association between proton pump inhibitor therapy and fatal C septicum infection.

46 CFR 56.50-30 - Boiler feed piping.

Code of Federal Regulations, 2014 CFR

2014-10-01

... pump may be used for other purposes. (2) If two independently driven pumps are provided, each capable... requirements. (1) Steam vessels, and motor vessels fitted with steam driven electrical generators shall have at... the necessary connections for this purpose. The arrangement of feed pumps shall be in accordance with...

Halophilic archaea on Earth and in space: growth and survival under extreme conditions.

PubMed

Oren, Aharon

2014-12-13

Salts are abundant on Mars, and any liquid water that is present or may have been present on the planet is expected to be hypersaline. Halophilic archaea (family Halobacteriaceae) are the microorganisms best adapted to life at extremes of salinity on Earth. This paper reviews the properties of the Halobacteriaceae that may make the group good candidates for life also on Mars. Many species resist high UV and gamma radiation levels; one species has survived exposure to vacuum and radiation during a space flight; and there is at least one psychrotolerant species. Halophilic archaea may survive for millions of years within brine inclusions in salt crystals. Many species have different modes of anaerobic metabolism, and some can use light as an energy source using the light-driven proton pump bacteriorhodopsin. They are also highly tolerant to perchlorate, recently shown to be present in Martian soils, and some species can even use perchlorate as an electron acceptor to support anaerobic growth. The presence of characteristic carotenoid pigments (α-bacterioruberin and derivatives) makes the Halobacteriaceae easy to identify by Raman spectroscopy. Thus, if present on Mars, such organisms may be detected by Raman instrumentation planned to explore Mars during the upcoming ExoMars mission. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

The Cytochrome b 6 f Complex: Biophysical Aspects of Its Functioning in Chloroplasts.

PubMed

Tikhonov, Alexander N

2018-01-01

This chapter presents an overview of structural properties of the cytochrome (Cyt) b 6 f complex and its functioning in chloroplasts. The Cyt b 6 f complex stands at the crossroad of photosynthetic electron transport pathways, providing connectivity between Photosystem (PSI) and Photosysten II (PSII) and pumping protons across the membrane into the thylakoid lumen. After a brief review of the chloroplast electron transport chain, the consideration is focused on the structural organization of the Cyt b 6 f complex and its interaction with plastoquinol (PQH 2 , reduced form of plastoquinone), a mediator of electron transfer from PSII to the Cyt b 6 f complex. The processes of PQH 2 oxidation by the Cyt b 6 f complex have been considered within the framework of the Mitchell's Q-cycle. The overall rate of the intersystem electron transport is determined by PQH 2 turnover at the quinone-binding site Q o of the Cyt b 6 f complex. The rate of PQH 2 oxidation is controlled by the intrathylakoid pH in , which value determines the protonation/deprotonation events in the Q o -center. Two other regulatory mechanisms associated with the Cyt b 6 f complex are briefly overviewed: (i) redistribution of electron fluxes between alternative (linear and cyclic) pathways, and (ii) "state transitions" related to redistribution of solar energy between PSI and PSII.

Structure of the membrane domain of respiratory complex I.

PubMed

Efremov, Rouslan G; Sazanov, Leonid A

2011-08-07

Complex I is the first and largest enzyme of the respiratory chain, coupling electron transfer between NADH and ubiquinone to the translocation of four protons across the membrane. It has a central role in cellular energy production and has been implicated in many human neurodegenerative diseases. The L-shaped enzyme consists of hydrophilic and membrane domains. Previously, we determined the structure of the hydrophilic domain. Here we report the crystal structure of the Esherichia coli complex I membrane domain at 3.0 Å resolution. It includes six subunits, NuoL, NuoM, NuoN, NuoA, NuoJ and NuoK, with 55 transmembrane helices. The fold of the homologous antiporter-like subunits L, M and N is novel, with two inverted structural repeats of five transmembrane helices arranged, unusually, face-to-back. Each repeat includes a discontinuous transmembrane helix and forms half of a channel across the membrane. A network of conserved polar residues connects the two half-channels, completing the proton translocation pathway. Unexpectedly, lysines rather than carboxylate residues act as the main elements of the proton pump in these subunits. The fourth probable proton-translocation channel is at the interface of subunits N, K, J and A. The structure indicates that proton translocation in complex I, uniquely, involves coordinated conformational changes in six symmetrical structural elements.

A Nonmetal Plasmonic Z-Scheme Photocatalyst with UV- to NIR-Driven Photocatalytic Protons Reduction.

PubMed

Zhang, Zhenyi; Huang, Jindou; Fang, Yurui; Zhang, Mingyi; Liu, Kuichao; Dong, Bin

2017-05-01

Ultrabroad-spectrum absorption and highly efficient generation of available charge carriers are two essential requirements for promising semiconductor-based photocatalysts, towards achieving the ultimate goal of solar-to-fuel conversion. Here, a fascinating nonmetal plasmonic Z-scheme photocatalyst with the W 18 O 49 /g-C 3 N 4 heterostructure is reported, which can effectively harvest photon energies spanning from the UV to the nearinfrared region and simultaneously possesses improved charge-carrier dynamics to boost the generation of long-lived active electrons for the photocatalytic reduction of protons into H 2 . By combining with theoretical simulations, a unique synergistic photocatalysis effect between the semiconductive Z-scheme charge-carrier separation and metal-like localized-surface-plasmon-resonance-induced "hot electrons" injection process is demonstrated within this binary heterostructure. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recent Observations and Modeling of Narrowband Stimulated Electromagnetic Emissions SEEs at HAARP and EISCAT

NASA Astrophysics Data System (ADS)

Scales, W.; Mahmoudian, A.; Fu, H.; Bordikar, M. R.; Samimi, A.; Bernhardt, P. A.; Briczinski, S. J., Jr.; Kosch, M. J.; Senior, A.; Isham, B.

2014-12-01

There has been significant interest in so-called narrowband Stimulated Electromagnetic Emission SEE over the past several years due to recent discoveries at the High Frequency Active Auroral Research Program HAARP facility near Gakone, Alaska. Narrowband SEE (NSEE) has been defined as spectral features in the SEE spectrum typically within 1 kHz of the transmitter (or pump) frequency. SEE is due to nonlinear processes leading to re-radiation at frequencies other than the pump wave frequency during heating the ionospheric plasma with high power HF radio waves. Although NSEE exhibits a richly complex structure, it has now been shown after a substantial number of observations at HAARP, that NSEE can be grouped into two basic classes. The first are those spectral features, associated with Stimulated Brillouin Scatter SBS, which typically occur when the pump frequency is not close to electron gyro-harmonic frequencies. Typically, these spectral features are within roughly 50 Hz of the pump wave frequency where it is to be noted that the O+ ion gyro-frequency is roughly 50 Hz. The second class of spectral features corresponds to the case when the pump wave frequency is typically within roughly 10 kHz of electron gyro-harmonic frequencies. In this case, spectral features ordered by harmonics of ion gyro-frequencies are typically observed, and termed Stimulated Ion Bernstein Scatter SIBS. This presentation will first provide an overview of the recent NSEE experimental observations at HAARP. Both Stimulated Brillouin Scatter SBS and Stimulated Ion Bernstein Scatter SIBS observations will be discussed as well as their relationship to each other. Possible theoretical formulation in terms of parametric decay instabilities and computational modeling will be provided. Possible applications of NSEE will be pointed out including triggering diagnostics for artificial ionization layer formation, proton precipitation event diagnostics, electron temperature measurements in the heated volume and detection of heavy ion species. Finally potential for observing such SEE at the European Incoherent Scatter EISCAT facility will be discussed.

Two-dimensional potential double layers and discrete auroras

NASA Technical Reports Server (NTRS)

Kan, J. R.; Lee, L. C.; Akasofu, S.-I.

1979-01-01

This paper is concerned with the formation of the acceleration region for electrons which produce the visible auroral arc and with the formation of the inverted V precipitation region. The former is embedded in the latter, and both are associated with field-aligned current sheets carried by plasma sheet electrons. It is shown that an electron current sheet driven from the plasma sheet into the ionosphere leads to the formation of a two-dimensional potential double layer. For a current sheet of a thickness less than the proton gyrodiameter solutions are obtained in which the field-aligned potential drop is distributed over a length much greater than the Debye length. For a current sheet of a thickness much greater than the proton gyrodiameter solutions are obtained in which the potential drop is confined to a distance on the order of the Debye length. The electric field in the two-dimensional double-layer model is the zeroth-order field inherent to the current sheet configuration, in contrast to those models in which the electric field is attributed to the first-order field due to current instabilities or turbulences. The maximum potential in the two-dimensional double-layer models is on the order of the thermal energy of plasma sheet protons, which ranges from 1 to 10 keV.

The Hydric Effect in Inorganic Nanomaterials for Nanoelectronics and Energy Applications.

PubMed

Sun, Xu; Guo, Yuqiao; Wu, Changzheng; Xie, Yi

2015-07-08

Protons, as one of the world's smallest ions, are able to trigger the charge effect without obvious lattice expansion inside inorganic materials, offering a unique and important test-bed for controlling their diverse functionalities. Arising from the high chemical reactivity of hydrogen (easily losing an electron) with various main group anions (easily accepting a proton), the hydric effect provides a convenient and environmentally benign route to bring about fascinating new physicochemical properties, as well as to create new inorganic structures based on the "old lattice" without dramatically destroying the pristine structure, covering most inorganic materials. Moreover, hydrogen atoms tend to bond with anions or to produce intrinsic defects, both of which are expected to inject extra electrons into lattice framework, promising advances in control of bandgap, spin behavior, and carrier concentration, which determine functionality for wide applications. In this review article, recently developed effective hydric strategies are highlighted, which include the conventional hydric reaction under high temperature or room temperature, proton irradiation or hydrogen plasma treatment, and gate-electrolyte-driven adsorption or doping. The diverse physicochemical properties brought by the hydric effect via modulation of the intrinsic electronic structure are also summarized, finding wide applications in nanoelectronics, energy applications, and catalysis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishiuchi, Mamiko; Pirozhkov, Alexander S.; Sakaki, Hironao

From the interaction between the high-contrast ({approx}more than 10{sup 10}) 130 TW Ti:sapphire laser pulse and Stainless Steel-2.5 um-thick tape target, proton beam with energies up to 23 MeV with the conversion efficiency of {approx}1% is obtained. After plasma mirror installation for contrast improvement, from the interaction between the 30 TW laser pulse and thin-foil target installed on the target holder with the hole whose shape is associated with the design of the well-known Wehnelt electrode of electron-gun, a 7 MeV intense proton beam is controlled dynamically and energy selected by the self-induced quasi-static electric field on the target holder.more » From the highly divergent beam having continuous spectrum, which are the typical features of the laser-driven proton beams from the interactions between the short-pulse laser and solid target, the spatial distribution of 7 MeV proton bunch is well manipulated to be focused to an small spots with an angular distribution of {approx}10 mrad. The number of protons included in the bunch is >10{sup 6}.« less

O2 reduction to H2O by the multicopper oxidases.

PubMed

Solomon, Edward I; Augustine, Anthony J; Yoon, Jungjoo

2008-08-14

In nature the four electron reduction of O2 to H2O is carried out by Cytochrome c oxidase (CcO) and the multicopper oxidases (MCOs). In the former, Cytochrome c provides electrons for pumping protons to produce a gradient for ATP synthesis, while in the MCOs the function is the oxidation of substrates, either organic or metal ions. In the MCOs the reduction of O2 is carried out at a trinuclear Cu cluster (TNC). Oxygen intermediates have been trapped which exhibit unique spectroscopic features that reflect novel geometric and electronic structures. These intermediates have both intact and cleaved O-O bonds, allowing the reductive cleavage of the O-O bond to be studied in detail both experimentally and computationally. These studies show that the topology of the TNC provides a unique geometric and electronic structure particularly suited to carry out this key reaction in nature.

O2 Reduction to H2O by the Multicopper Oxidases

PubMed Central

Solomon, Edward I.; Augustine, Anthony J.; Yoon, Jungjoo

2010-01-01

In nature the four electron reduction of O2 to H2O is carried out by Cytochrome c Oxidase (CcO) and the multicopper oxidases (MCOs). In the former, Cytochrome c provides electrons for pumping protons to produce a gradient for ATP synthesis, while in the MCOs the function is the oxidation of substrates, either organic or metal ions. In the MCOs the reduction of O2 is carried out at a trinuclear Cu cluster (TNC). Oxygen intermediates have been trapped which exhibit unique spectroscopic features that reflect novel geometric and electronic structures. These intermediates have both intact and cleaved O-O bonds, allowing the reductive cleavage of the O-O bond to be studied in detail both experimentally and computationally. These studies show that the topology of the TNC provides a unique geometric and electronic structure particularly suited to carry out this key reaction in Nature. PMID:18648693

Modelling of Electron and Proton Beams in a White-light Solar Flare

NASA Astrophysics Data System (ADS)

Milligan, R. O.; Procházka, O.; Reid, A.; Allred, J. C.; Mathioudakis, M.

2017-12-01

Observations of an X1 class WL solar flare on 2014 June 11 showed a surprisingly weak emission in both higher order Balmer and Lyman lines and continua. The flare was observed by RHESSI but low energy cut-off of non-thermal component was indeterminable due to the unusually hard electron spectrum (delta = 3). An estimate of power in non-thermal electron beams together with an area of WL emission observed by HMI yielded to an upper and lower estimate of flux 1E9 and 3E10 erg/cm2/s, respectively. We performed a grid of models using a radiative hydrodynamic code RADYN in order to compare synthetic spectra with observations. For low energy cut-off we chose a range from 20 to 120 keV with a step of 20 keV and delta parameter equal to 3. Electron beam-driven models show that higher low energy cut-off is more likely to produce an absorption Balmer line profile, if the total energy flux remains relatively low. On the other hand a detectable rise of HMI continuum (617 nm) lays a lower limit on the beam flux. Proton beam-driven models with equivalent fluxes indicate a greater penetration depth, while the Balmer lines reveal significantly weaker emission. Atmospheric temperature profiles show that for higher values of low energy cut-off the energy of the beam is deposited lower in chromosphere or even in temperature minimum region. This finding suggests, that suppressed hydrogen emission can indicate a formation of white-light continuum below chromosphere.

Small Bowel Bacterial Overgrowth Associated with Persistence of Abdominal Symptoms in Children Treated with a Proton Pump Inhibitor.

PubMed

Sieczkowska, Agnieszka; Landowski, Piotr; Zagozdzon, Pawel; Kaminska, Barbara; Lifschitz, Carlos

2015-05-01

Small bowel bacterial overgrowth (SBBO) was diagnosed in 22.5% of 40 children treated for 3 months with a proton pump inhibitor (PPI). Compared with those without SBBO, children with SBBO had higher frequency of abdominal pain, bloating, eructation, and flatulence. Patients with gastrointestinal symptoms after PPI treatment should be evaluated for SBBO rather than empirically prolonging PPI therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

The acidity of the tumor microenvironment is a mechanism of immune escape that can be overcome by proton pump inhibitors

PubMed Central

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

The relationship between long-term proton pump inhibitor therapy and skeletal frailty.

PubMed

Lau, Arthur N; Tomizza, Michael; Wong-Pack, Matthew; Papaioannou, Alexandra; Adachi, Jonathan D

2015-08-01

Proton pump inhibitors (PPIs) are a commonly prescribed class of medications. Their use has been associated with an increased rate of fractures, most notably hip fractures. However, there does not seem to be a clear association between PPI use and bone mineral density measurements, assessed by dual X-ray absorptiometry. The mechanism by which PPI use increases the risk of fractures remains unclear. This review will summarize the current evidence on this topic.

First observations of minority ion (H+) structuring in stimulated radiation during second electron gyroharmonic heating experiments

NASA Astrophysics Data System (ADS)

Bordikar, M. R.; Scales, W. A.; Samimi, A. R.; Bernhardt, P. A.; Brizcinski, S.; McCarrick, M. J.

2013-04-01

This work presents the first observations of unique narrowband emissions ordered near the hydrogen ion (H+) gyrofrequency (fcH) in the stimulated electromagnetic emission spectrum when the transmitter is tuned near the second electron gyroharmonic frequency (2fce) during ionospheric modification experiments. The frequency structuring of these newly discovered emission lines is quite unexpected since H+ is known to be a minor constituent in the interaction region which is near 160 km altitude. The spectral lines are typically shifted from the pump wave frequency by harmonics of a frequency about 10% less than fcH (≈ 800 Hz) and have a bandwidth of less than 50 Hz which is near the O+ gyrofrequency fcO. A theory is proposed to explain these emissions in terms of a parametric decay instability in a multi-ion species plasma due to possible proton precipitation associated with the disturbed conditions during the heating experiment. The observations can be explained by including several percent H+ ions into the background plasma. The implications are new possibilities for characterizing proton precipitation events during ionospheric heating experiments.

Proton pump inhibitors and the risk of severe adverse events - a cardiovascular bomb?

PubMed

Cunha, Nelson; Machado, António Pedro

2018-05-24

Proton pump inhibitors are currently one of the most prescribed pharmacological classes in developed countries, given their effectiveness and safety profile previously considered favourable. However, over the last few years, several papers have been published that associate prolonged use of these drugs with a wide range of adverse effects, posing doubts about their safety. Among the adverse effects described, one should emphasize the increased risk of cardiovascular events. This relationship was first described in subjects after acute coronary syndrome by the interference of proton pump inhibitors in cytochrome P450 2C19 and the conversion of clopidogrel to active metabolite. However, more recent studies describe this relationship also with the use of antiplatelet agents that do not depend on cytochrome P450 2C19 activation. The proposed mechanism is by inhibiting dimethylarginine dimethylaminohydrolase, a physiological inhibitor of asymmetric dimethylarginine, thus increasing the plasma concentrations of the latter enzyme and in turn translating into lower levels of nitric oxide. The authors reviewing in this article the relationship between the use of proton pump inhibitors and the increased risk of cardio and cerebrovascular events, are intended to alert the scientific community to the potentially harmful effects of these drugs and recommend the setting of a moratorium on their prolonged use. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Development of a Lead Slowing Down Spectrometer for fission cross section measurements at LANSCE

NASA Astrophysics Data System (ADS)

Rochman, Dimitri; Haight, Robert C.; Wender, Stephen A.; O'Donnell, John M.; Michaudon, Andre; Vieira, Dave J.; Rundberg, Robert S.; Kronenberg, Andreas; Bond, Evelyn; Wilhelmy, Jerry B.; Bredeweg, Todd; Ethvignot, Thierry; Granier, Thierry; Petit, Michael; Danon, Yaron

2004-05-01

The Lead Slowing Down Spectrometer (LSDS) recently installed at the Los Alamos Neutron Science Center (LANSCE) consists of a 1.2 meter cube of lead surrounding a tungsten target, which is bombarded by pulses of 800 MeV protons from the Proton Storage Ring (PSR). Neutrons are produced by spallation from the interaction of the proton pulse with the target. The aim of the LSDS is to keep the neutrons inside the lead volume for few hundreds of microseconds and to slow them down by small steps in energy before they leave the spectrometer. The advantage of the LSDS is the large amount of neutrons available in the lead volume compared to traditional time-of-flight experiments. Driving the LSDS with a pulsed proton beam increases the neutron flux per watt of beam power significantly over similar spectrometers driven by electron linear accelerators. The first measurements to characterize the properties of the LSDS are presented.

Insights into proton translocation in cbb3 oxidase from MD simulations.

PubMed

Carvalheda, Catarina A; Pisliakov, Andrei V

2017-05-01

Heme-copper oxidases are membrane protein complexes that catalyse the final step of the aerobic respiration, namely the reduction of oxygen to water. The energy released during catalysis is coupled to the active translocation of protons across the membrane, which contributes to the establishment of an electrochemical gradient that is used for ATP synthesis. The distinctive C-type (or cbb 3 ) cytochrome c oxidases, which are mostly present in proteobacteria, exhibit a number of unique structural and functional features, including high catalytic activity at low oxygen concentrations. At the moment, the functioning mechanism of C-type oxidases, in particular the proton transfer/pumping mechanism presumably via a single proton channel, is still poorly understood. In this work we used all-atom molecular dynamics simulations and continuum electrostatics calculations to obtain atomic-level insights into the hydration and dynamics of a cbb 3 oxidase. We provide the details of the water dynamics and proton transfer pathways for both the "chemical" and "pumped" protons, and show that formation of protonic connections is strongly affected by the protonation state of key residues, namely H243, E323 and H337. Copyright © 2017 Elsevier B.V. All rights reserved.

Measuring the temperature history of isochorically heated warm dense metals

NASA Astrophysics Data System (ADS)

McGuffey, Chris; Kim, J.; Park, J.; Moody, J.; Emig, J.; Heeter, B.; Dozieres, M.; Beg, Fn; McLean, Hs

2017-10-01

A pump-probe platform has been designed for soft X-ray absorption spectroscopy near edge structure measurements in isochorically heated Al or Cu samples with temperature of 10s to 100s of eV. The method is compatible with dual picosecond-class laser systems and may be used to measure the temperature of the sample heated directly by the pump laser or by a laser-driven proton beam Knowledge of the temperature history of warm dense samples will aid equation of state measurements. First, various low- to mid-Z targets were evaluated for their suitability as continuum X-ray backlighters over the range 200-1800 eV using a 10 J picosecond-class laser with relativistic peak intensity Alloys were found to be more suitable than single-element backlighters. Second, the heated sample package was designed with consideration of target thickness and tamp layers using atomic physics codes. The results of the first demonstration attempts will be presented. This work was supported by the U.S. DOE under Contract No. DE-SC0014600.

Measurement of the isolated diphoton cross section in pp collisions at s=7TeV with the ATLAS detector

NASA Astrophysics Data System (ADS)

Aad, G.; Abbott, B.; Abdallah, J.; Abdelalim, A. A.; Abdesselam, A.; Abdinov, O.; Abi, B.; Abolins, M.; Abramowicz, H.; Abreu, H.; Acerbi, E.; Acharya, B. S.; Adams, D. L.; Addy, T. N.; Adelman, J.; Aderholz, M.; Adomeit, S.; Adragna, P.; Adye, T.; Aefsky, S.; Aguilar-Saavedra, J. A.; Aharrouche, M.; Ahlen, S. P.; Ahles, F.; Ahmad, A.; Ahsan, M.; Aielli, G.; Akdogan, T.; Åkesson, T. P. A.; Akimoto, G.; Akimov, A. V.; Akiyama, A.; Alam, M. S.; Alam, M. A.; Albert, J.; Albrand, S.; Aleksa, M.; Aleksandrov, I. N.; Alessandria, F.; Alexa, C.; Alexander, G.; Alexandre, G.; Alexopoulos, T.; Alhroob, M.; Aliev, M.; Alimonti, G.; Alison, J.; Aliyev, M.; Allport, P. P.; Allwood-Spiers, S. E.; Almond, J.; Aloisio, A.; Alon, R.; Alonso, A.; Alviggi, M. G.; Amako, K.; Amaral, P.; Amelung, C.; Ammosov, V. V.; Amorim, A.; Amorós, G.; Amram, N.; Anastopoulos, C.; Andari, N.; Andeen, T.; Anders, C. F.; Anderson, K. J.; Andreazza, A.; Andrei, V.; Andrieux, M.-L.; Anduaga, X. S.; Angerami, A.; Anghinolfi, F.; Anjos, N.; Annovi, A.; Antonaki, A.; Antonelli, M.; Antonov, A.; Antos, J.; Anulli, F.; Aoun, S.; Aperio Bella, L.; Apolle, R.; Arabidze, G.; Aracena, I.; Arai, Y.; Arce, A. T. H.; Archambault, J. P.; Arfaoui, S.; Arguin, J.-F.; Arik, E.; Arik, M.; Armbruster, A. J.; Arnaez, O.; Arnault, C.; Artamonov, A.; Artoni, G.; Arutinov, D.; Asai, S.; Asfandiyarov, R.; Ask, S.; Åsman, B.; Asquith, L.; Assamagan, K.; Astbury, A.; Astvatsatourov, A.; Atoian, G.; Aubert, B.; Auerbach, B.; Auge, E.; Augsten, K.; Aurousseau, M.; Austin, N.; Avolio, G.; Avramidou, R.; Axen, D.; Ay, C.; Azuelos, G.; Azuma, Y.; Baak, M. A.; Baccaglioni, G.; Bacci, C.; Bach, A. M.; Bachacou, H.; Bachas, K.; Bachy, G.; Backes, M.; Backhaus, M.; Badescu, E.; Bagnaia, P.; Bahinipati, S.; Bai, Y.; Bailey, D. C.; Bain, T.; Baines, J. T.; Baker, O. K.; Baker, M. D.; Baker, S.; Baltasar Dos Santos Pedrosa, F.; Banas, E.; Banerjee, P.; Banerjee, Sw.; Banfi, D.; Bangert, A.; Bansal, V.; Bansil, H. S.; Barak, L.; Baranov, S. P.; Barashkou, A.; Barbaro Galtieri, A.; Barber, T.; Barberio, E. L.; Barberis, D.; Barbero, M.; Bardin, D. Y.; Barillari, T.; Barisonzi, M.; Barklow, T.; Barlow, N.; Barnett, B. M.; Barnett, R. M.; Baroncelli, A.; Barone, G.; Barr, A. J.; Barreiro, F.; Barreiro Guimarães da Costa, J.; Barrillon, P.; Bartoldus, R.; Barton, A. E.; Bartsch, D.; Bartsch, V.; Bates, R. L.; Batkova, L.; Batley, J. R.; Battaglia, A.; Battistin, M.; Battistoni, G.; Bauer, F.; Bawa, H. S.; Beare, B.; Beau, T.; Beauchemin, P. H.; Beccherle, R.; Bechtle, P.; Beck, H. P.; Beckingham, M.; Becks, K. H.; Beddall, A. J.; Beddall, A.; Bedikian, S.; Bednyakov, V. A.; Bee, C. P.; Begel, M.; Behar Harpaz, S.; Behera, P. K.; Beimforde, M.; Belanger-Champagne, C.; Bell, P. J.; Bell, W. H.; Bella, G.; Bellagamba, L.; Bellina, F.; Bellomo, M.; Belloni, A.; Beloborodova, O.; Belotskiy, K.; Beltramello, O.; Ben Ami, S.; Benary, O.; Benchekroun, D.; Benchouk, C.; Bendel, M.; Benedict, B. H.; Benekos, N.; Benhammou, Y.; Benjamin, D. P.; Benoit, M.; Bensinger, J. R.; Benslama, K.; Bentvelsen, S.; Berge, D.; Bergeaas Kuutmann, E.; Berger, N.; Berghaus, F.; Berglund, E.; Beringer, J.; Bernardet, K.; Bernat, P.; Bernhard, R.; Bernius, C.; Berry, T.; Bertin, A.; Bertinelli, F.; Bertolucci, F.; Besana, M. I.; Besson, N.; Bethke, S.; Bhimji, W.; Bianchi, R. M.; Bianco, M.; Biebel, O.; Bieniek, S. P.; Biesiada, J.; Biglietti, M.; Bilokon, H.; Bindi, M.; Binet, S.; Bingul, A.; Bini, C.; Biscarat, C.; Bitenc, U.; Black, K. M.; Blair, R. E.; Blanchard, J.-B.; Blanchot, G.; Blazek, T.; Blocker, C.; Blocki, J.; Blondel, A.; Blum, W.; Blumenschein, U.; Bobbink, G. J.; Bobrovnikov, V. B.; Bocchetta, S. S.; Bocci, A.; Boddy, C. R.; Boehler, M.; Boek, J.; Boelaert, N.; Böser, S.; Bogaerts, J. A.; Bogdanchikov, A.; Bogouch, A.; Bohm, C.; Boisvert, V.; Bold, T.; Boldea, V.; Bolnet, N. M.; Bona, M.; Bondarenko, V. G.; Boonekamp, M.; Boorman, G.; Booth, C. N.; Bordoni, S.; Borer, C.; Borisov, A.; Borissov, G.; Borjanovic, I.; Borroni, S.; Bos, K.; Boscherini, D.; Bosman, M.; Boterenbrood, H.; Botterill, D.; Bouchami, J.; Boudreau, J.; Bouhova-Thacker, E. V.; Boulahouache, C.; Bourdarios, C.; Bousson, N.; Boveia, A.; Boyd, J.; Boyko, I. R.; Bozhko, N. I.; Bozovic-Jelisavcic, I.; Bracinik, J.; Braem, A.; Branchini, P.; Brandenburg, G. W.; Brandt, A.; Brandt, G.; Brandt, O.; Bratzler, U.; Brau, B.; Brau, J. E.; Braun, H. M.; Brelier, B.; Bremer, J.; Brenner, R.; Bressler, S.; Breton, D.; Britton, D.; Brochu, F. M.; Brock, I.; Brock, R.; Brodbeck, T. J.; Brodet, E.; Broggi, F.; Bromberg, C.; Brooijmans, G.; Brooks, W. K.; Brown, G.; Brown, H.; Bruckman de Renstrom, P. A.; Bruncko, D.; Bruneliere, R.; Brunet, S.; Bruni, A.; Bruni, G.; Bruschi, M.; Buanes, T.; Buat, Q.; Bucci, F.; Buchanan, J.; Buchanan, N. J.; Buchholz, P.; Buckingham, R. M.; Buckley, A. G.; Buda, S. I.; Budagov, I. A.; Budick, B.; Büscher, V.; Bugge, L.; Buira-Clark, D.; Bulekov, O.; Bunse, M.; Buran, T.; Burckhart, H.; Burdin, S.; Burgess, T.; Burke, S.; Busato, E.; Bussey, P.; Buszello, C. P.; Butin, F.; Butler, B.; Butler, J. M.; Buttar, C. M.; Butterworth, J. M.; Buttinger, W.; Byatt, T.; Cabrera Urbán, S.; Caforio, D.; Cakir, O.; Calafiura, P.; Calderini, G.; Calfayan, P.; Calkins, R.; Caloba, L. P.; Caloi, R.; Calvet, D.; Calvet, S.; Camacho Toro, R.; Camarri, P.; Cambiaghi, M.; Cameron, D.; Campana, S.; Campanelli, M.; Canale, V.; Canelli, F.; Canepa, A.; Cantero, J.; Capasso, L.; Capeans Garrido, M. D. M.; Caprini, I.; Caprini, M.; Capriotti, D.; Capua, M.; Caputo, R.; Caramarcu, C.; Cardarelli, R.; Carli, T.; Carlino, G.; Carminati, L.; Caron, B.; Caron, S.; Carrillo Montoya, G. D.; Carter, A. A.; Carter, J. R.; Carvalho, J.; Casadei, D.; Casado, M. P.; Cascella, M.; Caso, C.; Castaneda Hernandez, A. M.; Castaneda-Miranda, E.; Castillo Gimenez, V.; Castro, N. F.; Cataldi, G.; Cataneo, F.; Catinaccio, A.; Catmore, J. R.; Cattai, A.; Cattani, G.; Caughron, S.; Cauz, D.; Cavalleri, P.; Cavalli, D.; Cavalli-Sforza, M.; Cavasinni, V.; Ceradini, F.; Cerqueira, A. S.; Cerri, A.; Cerrito, L.; Cerutti, F.; Cetin, S. A.; Cevenini, F.; Chafaq, A.; Chakraborty, D.; Chan, K.; Chapleau, B.; Chapman, J. D.; Chapman, J. W.; Chareyre, E.; Charlton, D. G.; Chavda, V.; Chavez Barajas, C. A.; Cheatham, S.; Chekanov, S.; Chekulaev, S. V.; Chelkov, G. A.; Chelstowska, M. A.; Chen, C.; Chen, H.; Chen, S.; Chen, T.; Chen, X.; Cheng, S.; Cheplakov, A.; Chepurnov, V. F.; Cherkaoui El Moursli, R.; Chernyatin, V.; Cheu, E.; Cheung, S. L.; Chevalier, L.; Chiefari, G.; Chikovani, L.; Childers, J. T.; Chilingarov, A.; Chiodini, G.; Chizhov, M. V.; Choudalakis, G.; Chouridou, S.; Christidi, I. A.; Christov, A.; Chromek-Burckhart, D.; Chu, M. L.; Chudoba, J.; Ciapetti, G.; Ciba, K.; Ciftci, A. K.; Ciftci, R.; Cinca, D.; Cindro, V.; Ciobotaru, M. D.; Ciocca, C.; Ciocio, A.; Cirilli, M.; Ciubancan, M.; Clark, A.; Clark, P. J.; Cleland, W.; Clemens, J. C.; Clement, B.; Clement, C.; Clifft, R. W.; Coadou, Y.; Cobal, M.; Coccaro, A.; Cochran, J.; Coe, P.; Cogan, J. G.; Coggeshall, J.; Cogneras, E.; Cojocaru, C. D.; Colas, J.; Colijn, A. P.; Collard, C.; Collins, N. J.; Collins-Tooth, C.; Collot, J.; Colon, G.; Conde Muiño, P.; Coniavitis, E.; Conidi, M. C.; Consonni, M.; Consorti, V.; Constantinescu, S.; Conta, C.; Conventi, F.; Cook, J.; Cooke, M.; Cooper, B. D.; Cooper-Sarkar, A. M.; Cooper-Smith, N. J.; Copic, K.; Cornelissen, T.; Corradi, M.; Corriveau, F.; Cortes-Gonzalez, A.; Cortiana, G.; Costa, G.; Costa, M. J.; Costanzo, D.; Costin, T.; Côté, D.; Coura Torres, R.; Courneyea, L.; Cowan, G.; Cowden, C.; Cox, B. E.; Cranmer, K.; Crescioli, F.; Cristinziani, M.; Crosetti, G.; Crupi, R.; Crépé-Renaudin, S.; Cuciuc, C.-M.; Cuenca Almenar, C.; Cuhadar Donszelmann, T.; Cuneo, S.; Curatolo, M.; Curtis, C. J.; Cwetanski, P.; Czirr, H.; Czyczula, Z.; D'Auria, S.; D'Onofrio, M.; D'Orazio, A.; da Silva, P. V. M.; da Via, C.; Dabrowski, W.; Dai, T.; Dallapiccola, C.; Dam, M.; Dameri, M.; Damiani, D. S.; Danielsson, H. O.; Dannheim, D.; Dao, V.; Darbo, G.; Darlea, G. L.; Daum, C.; Dauvergne, J. P.; Davey, W.; Davidek, T.; Davidson, N.; Davidson, R.; Davies, E.; Davies, M.; Davignon, O. A.; Davison, A. R.; Davygora, Y.; Dawe, E.; Dawson, I.; Dawson, J. W.; Daya, R. K.; de, K.; de Asmundis, R.; de Castro, S.; de Castro Faria Salgado, P. E.; de Cecco, S.; de Graat, J.; de Groot, N.; de Jong, P.; de La Taille, C.; de la Torre, H.; de Lotto, B.; de Mora, L.; de Nooij, L.; de Oliveira Branco, M.; de Pedis, D.; de Saintignon, P.; de Salvo, A.; de Sanctis, U.; de Santo, A.; de Vivie de Regie, J. B.; Dean, S.; Dedovich, D. V.; Degenhardt, J.; Dehchar, M.; Deile, M.; Del Papa, C.; Del Peso, J.; Del Prete, T.; Deliyergiyev, M.; Dell'Acqua, A.; Dell'Asta, L.; Della Pietra, M.; Della Volpe, D.; Delmastro, M.; Delpierre, P.; Delruelle, N.; Delsart, P. A.; Deluca, C.; Demers, S.; Demichev, M.; Demirkoz, B.; Deng, J.; Denisov, S. P.; Derendarz, D.; Derkaoui, J. E.; Derue, F.; Dervan, P.; Desch, K.; Devetak, E.; Deviveiros, P. O.; Dewhurst, A.; Dewilde, B.; Dhaliwal, S.; Dhullipudi, R.; di Ciaccio, A.; di Ciaccio, L.; di Girolamo, A.; di Girolamo, B.; di Luise, S.; di Mattia, A.; di Micco, B.; di Nardo, R.; di Simone, A.; di Sipio, R.; Diaz, M. A.; Diblen, F.; Diehl, E. B.; Dietrich, J.; Dietzsch, T. A.; Diglio, S.; Dindar Yagci, K.; Dingfelder, J.; Dionisi, C.; Dita, P.; Dita, S.; Dittus, F.; Djama, F.; Djobava, T.; Do Vale, M. A. B.; Do Valle Wemans, A.; Doan, T. K. O.; Dobbs, M.; Dobinson, R.; Dobos, D.; Dobson, E.; Dobson, M.; Dodd, J.; Doglioni, C.; Doherty, T.; Doi, Y.; Dolejsi, J.; Dolenc, I.; Dolezal, Z.; Dolgoshein, B. A.; Dohmae, T.; Donadelli, M.; Donega, M.; Donini, J.; Dopke, J.; Doria, A.; Dos Anjos, A.; Dosil, M.; Dotti, A.; Dova, M. T.; Dowell, J. D.; Doxiadis, A. D.; Doyle, A. T.; Drasal, Z.; Drees, J.; Dressnandt, N.; Drevermann, H.; Driouichi, C.; Dris, M.; Dubbert, J.; Dubbs, T.; Dube, S.; Duchovni, E.; Duckeck, G.; Dudarev, A.; Dudziak, F.; Dührssen, M.; Duerdoth, I. P.; Duflot, L.; Dufour, M.-A.; Dunford, M.; Duran Yildiz, H.; Duxfield, R.; Dwuznik, M.; Dydak, F.; Dzahini, D.; Düren, M.; Ebenstein, W. L.; Ebke, J.; Eckert, S.; Eckweiler, S.; Edmonds, K.; Edwards, C. A.; Edwards, N. C.; Ehrenfeld, W.; Ehrich, T.; Eifert, T.; Eigen, G.; Einsweiler, K.; Eisenhandler, E.; Ekelof, T.; El Kacimi, M.; Ellert, M.; Elles, S.; Ellinghaus, F.; Ellis, K.; Ellis, N.; Elmsheuser, J.; Elsing, M.; Ely, R.; Emeliyanov, D.; Engelmann, R.; Engl, A.; Epp, B.; Eppig, A.; Erdmann, J.; Ereditato, A.; Eriksson, D.; Ernst, J.; Ernst, M.; Ernwein, J.; Errede, D.; Errede, S.; Ertel, E.; Escalier, M.; Escobar, C.; Espinal Curull, X.; Esposito, B.; Etienne, F.; Etienvre, A. I.; Etzion, E.; Evangelakou, D.; Evans, H.; Fabbri, L.; Fabre, C.; Fakhrutdinov, R. M.; Falciano, S.; Fang, Y.; Fanti, M.; Farbin, A.; Farilla, A.; Farley, J.; Farooque, T.; Farrington, S. M.; Farthouat, P.; Fassnacht, P.; Fassouliotis, D.; Fatholahzadeh, B.; Favareto, A.; Fayard, L.; Fazio, S.; Febbraro, R.; Federic, P.; Fedin, O. L.; Fedorko, W.; Fehling-Kaschek, M.; Feligioni, L.; Fellmann, D.; Felzmann, C. U.; Feng, C.; Feng, E. J.; Fenyuk, A. B.; Ferencei, J.; Ferland, J.; Fernando, W.; Ferrag, S.; Ferrando, J.; Ferrara, V.; Ferrari, A.; Ferrari, P.; Ferrari, R.; Ferrer, A.; Ferrer, M. L.; Ferrere, D.; Ferretti, C.; Ferretto Parodi, A.; Fiascaris, M.; Fiedler, F.; Filipčič, A.; Filippas, A.; Filthaut, F.; Fincke-Keeler, M.; Fiolhais, M. C. N.; Fiorini, L.; Firan, A.; Fischer, G.; Fischer, P.; Fisher, M. J.; Fisher, S. M.; Flechl, M.; Fleck, I.; Fleckner, J.; Fleischmann, P.; Fleischmann, S.; Flick, T.; Flores Castillo, L. R.; Flowerdew, M. J.; Föhlisch, F.; Fokitis, M.; Fonseca Martin, T.; Forbush, D. A.; Formica, A.; Forti, A.; Fortin, D.; Foster, J. M.; Fournier, D.; Foussat, A.; Fowler, A. J.; Fowler, K.; Fox, H.; Francavilla, P.; Franchino, S.; Francis, D.; Frank, T.; Franklin, M.; Franz, S.; Fraternali, M.; Fratina, S.; French, S. T.; Froeschl, R.; Froidevaux, D.; Frost, J. A.; Fukunaga, C.; Fullana Torregrosa, E.; Fuster, J.; Gabaldon, C.; Gabizon, O.; Gadfort, T.; Gadomski, S.; Gagliardi, G.; Gagnon, P.; Galea, C.; Gallas, E. J.; Gallas, M. V.; Gallo, V.; Gallop, B. J.; Gallus, P.; Galyaev, E.; Gan, K. K.; Gao, Y. S.; Gapienko, V. A.; Gaponenko, A.; Garberson, F.; Garcia-Sciveres, M.; García, C.; García Navarro, J. E.; Gardner, R. W.; Garelli, N.; Garitaonandia, H.; Garonne, V.; Garvey, J.; Gatti, C.; Gaudio, G.; Gaumer, O.; Gaur, B.; Gauthier, L.; Gavrilenko, I. L.; Gay, C.; Gaycken, G.; Gayde, J.-C.; Gazis, E. N.; Ge, P.; Gee, C. N. P.; Geerts, D. A. A.; Geich-Gimbel, Ch.; Gellerstedt, K.; Gemme, C.; Gemmell, A.; Genest, M. H.; Gentile, S.; George, M.; George, S.; Gerlach, P.; Gershon, A.; Geweniger, C.; Ghazlane, H.; Ghez, P.; Ghodbane, N.; Giacobbe, B.; Giagu, S.; Giakoumopoulou, V.; Giangiobbe, V.; Gianotti, F.; Gibbard, B.; Gibson, A.; Gibson, S. M.; Gilbert, L. M.; Gilchriese, M.; Gilewsky, V.; Gillberg, D.; Gillman, A. R.; Gingrich, D. M.; Ginzburg, J.; Giokaris, N.; Giordano, R.; Giorgi, F. M.; Giovannini, P.; Giraud, P. F.; Giugni, D.; Giunta, M.; Giusti, P.; Gjelsten, B. K.; Gladilin, L. K.; Glasman, C.; Glatzer, J.; Glazov, A.; Glitza, K. W.; Glonti, G. L.; Godfrey, J.; Godlewski, J.; Goebel, M.; Göpfert, T.; Goeringer, C.; Gössling, C.; Göttfert, T.; Goldfarb, S.; Goldin, D.; Golling, T.; Golovnia, S. N.; Gomes, A.; Gomez Fajardo, L. S.; Gonçalo, R.; Goncalves Pinto Firmino da Costa, J.; Gonella, L.; Gonidec, A.; Gonzalez, S.; González de La Hoz, S.; Gonzalez Silva, M. L.; Gonzalez-Sevilla, S.; Goodson, J. J.; Goossens, L.; Gorbounov, P. A.; Gordon, H. A.; Gorelov, I.; Gorfine, G.; Gorini, B.; Gorini, E.; Gorišek, A.; Gornicki, E.; Gorokhov, S. A.; Goryachev, V. N.; Gosdzik, B.; Gosselink, M.; Gostkin, M. I.; Gouanère, M.; Gough Eschrich, I.; Gouighri, M.; Goujdami, D.; Goulette, M. P.; Goussiou, A. G.; Goy, C.; Grabowska-Bold, I.; Grabski, V.; Grafström, P.; Grah, C.; Grahn, K.-J.; Grancagnolo, F.; Grancagnolo, S.; Grassi, V.; Gratchev, V.; Grau, N.; Gray, H. M.; Gray, J. A.; Graziani, E.; Grebenyuk, O. G.; Greenfield, D.; Greenshaw, T.; Greenwood, Z. D.; Gregor, I. M.; Grenier, P.; Griffiths, J.; Grigalashvili, N.; Grillo, A. A.; Grinstein, S.; Grishkevich, Y. V.; Grivaz, J.-F.; Grognuz, J.; Groh, M.; Gross, E.; Grosse-Knetter, J.; Groth-Jensen, J.; Grybel, K.; Guarino, V. J.; Guest, D.; Guicheney, C.; Guida, A.; Guillemin, T.; Guindon, S.; Guler, H.; Gunther, J.; Guo, B.; Guo, J.; Gupta, A.; Gusakov, Y.; Gushchin, V. N.; Gutierrez, A.; Gutierrez, P.; Guttman, N.; Gutzwiller, O.; Guyot, C.; Gwenlan, C.; Gwilliam, C. B.; Haas, A.; Haas, S.; Haber, C.; Hackenburg, R.; Hadavand, H. K.; Hadley, D. R.; Haefner, P.; Hahn, F.; Haider, S.; Hajduk, Z.; Hakobyan, H.; Haller, J.; Hamacher, K.; Hamal, P.; Hamilton, A.; Hamilton, S.; Han, H.; Han, L.; Hanagaki, K.; Hance, M.; Handel, C.; Hanke, P.; Hansen, J. R.; Hansen, J. B.; Hansen, J. D.; Hansen, P. H.; Hansson, P.; Hara, K.; Hare, G. A.; Harenberg, T.; Harkusha, S.; Harper, D.; Harrington, R. D.; Harris, O. M.; Harrison, K.; Hartert, J.; Hartjes, F.; Haruyama, T.; Harvey, A.; Hasegawa, S.; Hasegawa, Y.; Hassani, S.; Hatch, M.; Hauff, D.; Haug, S.; Hauschild, M.; Hauser, R.; Havranek, M.; Hawes, B. M.; Hawkes, C. M.; Hawkings, R. J.; Hawkins, D.; Hayakawa, T.; Hayden, D.; Hayward, H. S.; Haywood, S. J.; Hazen, E.; He, M.; Head, S. J.; Hedberg, V.; Heelan, L.; Heim, S.; Heinemann, B.; Heisterkamp, S.; Helary, L.; Heller, M.; Hellman, S.; Hellmich, D.; Helsens, C.; Henderson, R. C. W.; Henke, M.; Henrichs, A.; Henriques Correia, A. M.; Henrot-Versille, S.; Henry-Couannier, F.; Hensel, C.; Henß, T.; Hernandez, C. M.; Hernández Jiménez, Y.; Herrberg, R.; Hershenhorn, A. D.; Herten, G.; Hertenberger, R.; Hervas, L.; Hessey, N. P.; Hidvegi, A.; Higón-Rodriguez, E.; Hill, D.; Hill, J. C.; Hill, N.; Hiller, K. H.; Hillert, S.; Hillier, S. J.; Hinchliffe, I.; Hines, E.; Hirose, M.; Hirsch, F.; Hirschbuehl, D.; Hobbs, J.; Hod, N.; Hodgkinson, M. C.; Hodgson, P.; Hoecker, A.; Hoeferkamp, M. R.; Hoffman, J.; Hoffmann, D.; Hohlfeld, M.; Holder, M.; Holmes, A.; Holmgren, S. O.; Holy, T.; Holzbauer, J. L.; Homma, Y.; Hong, T. M.; Hooft van Huysduynen, L.; Horazdovsky, T.; Horn, C.; Horner, S.; Horton, K.; Hostachy, J.-Y.; Hou, S.; Houlden, M. A.; Hoummada, A.; Howarth, J.; Howell, D. F.; Hristova, I.; Hrivnac, J.; Hruska, I.; Hryn'Ova, T.; Hsu, P. J.; Hsu, S.-C.; Huang, G. S.; Hubacek, Z.; Hubaut, F.; Huegging, F.; Huffman, T. B.; Hughes, E. W.; Hughes, G.; Hughes-Jones, R. E.; Huhtinen, M.; Hurst, P.; Hurwitz, M.; Husemann, U.; Huseynov, N.; Huston, J.; Huth, J.; Iacobucci, G.; Iakovidis, G.; Ibbotson, M.; Ibragimov, I.; Ichimiya, R.; Iconomidou-Fayard, L.; Idarraga, J.; Idzik, M.; Iengo, P.; Igonkina, O.; Ikegami, Y.; Ikeno, M.; Ilchenko, Y.; Iliadis, D.; Imbault, D.; Imhaeuser, M.; Imori, M.; Ince, T.; Inigo-Golfin, J.; Ioannou, P.; Iodice, M.; Ionescu, G.; Irles Quiles, A.; Ishii, K.; Ishikawa, A.; Ishino, M.; Ishmukhametov, R.; Issever, C.; Istin, S.; Itoh, Y.; Ivashin, A. V.; Iwanski, W.; Iwasaki, H.; Izen, J. M.; Izzo, V.; Jackson, B.; Jackson, J. N.; Jackson, P.; Jaekel, M. R.; Jain, V.; Jakobs, K.; Jakobsen, S.; Jakubek, J.; Jana, D. K.; Jankowski, E.; Jansen, E.; Jantsch, A.; Janus, M.; Jarlskog, G.; Jeanty, L.; Jelen, K.; Jen-La Plante, I.; Jenni, P.; Jeremie, A.; Jež, P.; Jézéquel, S.; Jha, M. K.; Ji, H.; Ji, W.; Jia, J.; Jiang, Y.; Jimenez Belenguer, M.; Jin, G.; Jin, S.; Jinnouchi, O.; Joergensen, M. D.; Joffe, D.; Johansen, L. G.; Johansen, M.; Johansson, K. E.; Johansson, P.; Johnert, S.; Johns, K. A.; Jon-And, K.; Jones, G.; Jones, R. W. L.; Jones, T. W.; Jones, T. J.; Jonsson, O.; Joram, C.; Jorge, P. M.; Joseph, J.; Jovin, T.; Ju, X.; Juranek, V.; Jussel, P.; Kabachenko, V. V.; Kabana, S.; Kaci, M.; Kaczmarska, A.; Kadlecik, P.; Kado, M.; Kagan, H.; Kagan, M.; Kaiser, S.; Kajomovitz, E.; Kalinin, S.; Kalinovskaya, L. V.; Kama, S.; Kanaya, N.; Kaneda, M.; Kanno, T.; Kantserov, V. A.; Kanzaki, J.; Kaplan, B.; Kapliy, A.; Kaplon, J.; Kar, D.; Karagoz, M.; Karnevskiy, M.; Karr, K.; Kartvelishvili, V.; Karyukhin, A. N.; Kashif, L.; Kasmi, A.; Kass, R. D.; Kastanas, A.; Kataoka, M.; Kataoka, Y.; Katsoufis, E.; Katzy, J.; Kaushik, V.; Kawagoe, K.; Kawamoto, T.; Kawamura, G.; Kayl, M. S.; Kazanin, V. A.; Kazarinov, M. Y.; Keates, J. R.; Keeler, R.; Kehoe, R.; Keil, M.; Kekelidze, G. D.; Kelly, M.; Kennedy, J.; Kenney, C. J.; Kenyon, M.; Kepka, O.; Kerschen, N.; Kerševan, B. P.; Kersten, S.; Kessoku, K.; Ketterer, C.; Keung, J.; Khakzad, M.; Khalil-Zada, F.; Khandanyan, H.; Khanov, A.; Kharchenko, D.; Khodinov, A.; Kholodenko, A. G.; Khomich, A.; Khoo, T. J.; Khoriauli, G.; Khoroshilov, A.; Khovanskiy, N.; Khovanskiy, V.; Khramov, E.; Khubua, J.; Kim, H.; Kim, M. S.; Kim, P. C.; Kim, S. H.; Kimura, N.; Kind, O.; King, B. T.; King, M.; King, R. S. B.; Kirk, J.; Kirsch, G. P.; Kirsch, L. E.; Kiryunin, A. E.; Kisielewska, D.; Kittelmann, T.; Kiver, A. M.; Kiyamura, H.; Kladiva, E.; Klaiber-Lodewigs, J.; Klein, M.; Klein, U.; Kleinknecht, K.; Klemetti, M.; Klier, A.; Klimentov, A.; Klingenberg, R.; Klinkby, E. B.; Klioutchnikova, T.; Klok, P. F.; Klous, S.; Kluge, E.-E.; Kluge, T.; Kluit, P.; Kluth, S.; Kneringer, E.; Knobloch, J.; Knoops, E. B. F. G.; Knue, A.; Ko, B. R.; Kobayashi, T.; Kobel, M.; Kocian, M.; Kocnar, A.; Kodys, P.; Köneke, K.; König, A. C.; Koenig, S.; Köpke, L.; Koetsveld, F.; Koevesarki, P.; Koffas, T.; Koffeman, E.; Kohn, F.; Kohout, Z.; Kohriki, T.; Koi, T.; Kokott, T.; Kolachev, G. M.; Kolanoski, H.; Kolesnikov, V.; Koletsou, I.; Koll, J.; Kollar, D.; Kollefrath, M.; Kolya, S. D.; Komar, A. A.; Komaragiri, J. R.; Komori, Y.; Kondo, T.; Kono, T.; Kononov, A. I.; Konoplich, R.; Konstantinidis, N.; Kootz, A.; Koperny, S.; Kopikov, S. V.; Korcyl, K.; Kordas, K.; Koreshev, V.; Korn, A.; Korol, A.; Korolkov, I.; Korolkova, E. V.; Korotkov, V. A.; Kortner, O.; Kortner, S.; Kostyukhin, V. V.; Kotamäki, M. J.; Kotov, S.; Kotov, V. M.; Kotwal, A.; Kourkoumelis, C.; Kouskoura, V.; Koutsman, A.; Kowalewski, R.; Kowalski, T. Z.; Kozanecki, W.; Kozhin, A. S.; Kral, V.; Kramarenko, V. A.; Kramberger, G.; Krasel, O.; Krasny, M. W.; Krasznahorkay, A.; Kraus, J.; Kreisel, A.; Krejci, F.; Kretzschmar, J.; Krieger, N.; Krieger, P.; Kroeninger, K.; Kroha, H.; Kroll, J.; Kroseberg, J.; Krstic, J.; Kruchonak, U.; Krüger, H.; Kruker, T.; Krumshteyn, Z. V.; Kruth, A.; Kubota, T.; Kuehn, S.; Kugel, A.; Kuhl, T.; Kuhn, D.; Kukhtin, V.; Kulchitsky, Y.; Kuleshov, S.; Kummer, C.; Kuna, M.; Kundu, N.; Kunkle, J.; Kupco, A.; Kurashige, H.; Kurata, M.; Kurochkin, Y. A.; Kus, V.; Kuykendall, W.; Kuze, M.; Kuzhir, P.; Kvasnicka, O.; Kvita, J.; Kwee, R.; La Rosa, A.; La Rotonda, L.; Labarga, L.; Labbe, J.; Lablak, S.; Lacasta, C.; Lacava, F.; Lacker, H.; Lacour, D.; Lacuesta, V. R.; Ladygin, E.; Lafaye, R.; Laforge, B.; Lagouri, T.; Lai, S.; Laisne, E.; Lamanna, M.; Lampen, C. L.; Lampl, W.; Lancon, E.; Landgraf, U.; Landon, M. P. J.; Landsman, H.; Lane, J. L.; Lange, C.; Lankford, A. J.; Lanni, F.; Lantzsch, K.; Laplace, S.; Lapoire, C.; Laporte, J. F.; Lari, T.; Larionov, A. V.; Larner, A.; Lasseur, C.; Lassnig, M.; Lau, W.; Laurelli, P.; Lavorato, A.; Lavrijsen, W.; Laycock, P.; Lazarev, A. B.; Lazzaro, A.; Le Dortz, O.; Le Guirriec, E.; Le Maner, C.; Le Menedeu, E.; Lebel, C.; Lecompte, T.; Ledroit-Guillon, F.; Lee, H.; Lee, J. S. H.; Lee, S. C.; Lee, L.; Lefebvre, M.; Legendre, M.; Leger, A.; Legeyt, B. C.; Legger, F.; Leggett, C.; Lehmacher, M.; Lehmann Miotto, G.; Lei, X.; Leite, M. A. L.; Leitner, R.; Lellouch, D.; Lellouch, J.; Leltchouk, M.; Lendermann, V.; Leney, K. J. C.; Lenz, T.; Lenzen, G.; Lenzi, B.; Leonhardt, K.; Leontsinis, S.; Leroy, C.; Lessard, J.-R.; Lesser, J.; Lester, C. G.; Leung Fook Cheong, A.; Levêque, J.; Levin, D.; Levinson, L. J.; Levitski, M. S.; Lewandowska, M.; Lewis, A.; Lewis, G. H.; Leyko, A. M.; Leyton, M.; Li, B.; Li, H.; Li, S.; Li, X.; Liang, Z.; Liang, Z.; Liberti, B.; Lichard, P.; Lichtnecker, M.; Lie, K.; Liebig, W.; Lifshitz, R.; Lilley, J. N.; Limbach, C.; Limosani, A.; Limper, M.; Lin, S. C.; Linde, F.; Linnemann, J. T.; Lipeles, E.; Lipinsky, L.; Lipniacka, A.; Liss, T. M.; Lissauer, D.; Lister, A.; Litke, A. M.; Liu, C.; Liu, D.; Liu, H.; Liu, J. B.; Liu, M.; Liu, S.; Liu, Y.; Livan, M.; Livermore, S. S. A.; Lleres, A.; Llorente Merino, J.; Lloyd, S. L.; Lobodzinska, E.; Loch, P.; Lockman, W. S.; Lockwitz, S.; Loddenkoetter, T.; Loebinger, F. K.; Loginov, A.; Loh, C. W.; Lohse, T.; Lohwasser, K.; Lokajicek, M.; Loken, J.; Lombardo, V. P.; Long, R. E.; Lopes, L.; Lopez Mateos, D.; Losada, M.; Loscutoff, P.; Lo Sterzo, F.; Losty, M. J.; Lou, X.; Lounis, A.; Loureiro, K. F.; Love, J.; Love, P. A.; Lowe, A. J.; Lu, F.; Lubatti, H. J.; Luci, C.; Lucotte, A.; Ludwig, A.; Ludwig, D.; Ludwig, I.; Ludwig, J.; Luehring, F.; Luijckx, G.; Lumb, D.; Luminari, L.; Lund, E.; Lund-Jensen, B.; Lundberg, B.; Lundberg, J.; Lundquist, J.; Lungwitz, M.; Lupi, A.; Lutz, G.; Lynn, D.; Lys, J.; Lytken, E.; Ma, H.; Ma, L. L.; Macana Goia, J. A.; Maccarrone, G.; Macchiolo, A.; Maček, B.; Machado Miguens, J.; Macina, D.; Mackeprang, R.; Madaras, R. J.; Mader, W. F.; Maenner, R.; Maeno, T.; Mättig, P.; Mättig, S.; Magalhaes Martins, P. J.; Magnoni, L.; Magradze, E.; Mahalalel, Y.; Mahboubi, K.; Mahout, G.; Maiani, C.; Maidantchik, C.; Maio, A.; Majewski, S.; Makida, Y.; Makovec, N.; Mal, P.; Malecki, Pa.; Malecki, P.; Maleev, V. P.; Malek, F.; Mallik, U.; Malon, D.; Maltezos, S.; Malyshev, V.; Malyukov, S.; Mameghani, R.; Mamuzic, J.; Manabe, A.; Mandelli, L.; Mandić, I.; Mandrysch, R.; Maneira, J.; Mangeard, P. S.; Manjavidze, I. D.; Mann, A.; Manning, P. M.; Manousakis-Katsikakis, A.; Mansoulie, B.; Manz, A.; Mapelli, A.; Mapelli, L.; March, L.; Marchand, J. F.; Marchese, F.; Marchiori, G.; Marcisovsky, M.; Marin, A.; Marino, C. P.; Marroquim, F.; Marshall, R.; Marshall, Z.; Martens, F. K.; Marti-Garcia, S.; Martin, A. J.; Martin, B.; Martin, B.; Martin, F. F.; Martin, J. P.; Martin, Ph.; Martin, T. A.; Martin Dit Latour, B.; Martinez, M.; Martinez Outschoorn, V.; Martyniuk, A. C.; Marx, M.; Marzano, F.; Marzin, A.; Masetti, L.; Mashimo, T.; Mashinistov, R.; Masik, J.; Maslennikov, A. L.; Maß, M.; Massa, I.; Massaro, G.; Massol, N.; Mastrandrea, P.; Mastroberardino, A.; Masubuchi, T.; Mathes, M.; Matricon, P.; Matsumoto, H.; Matsunaga, H.; Matsushita, T.; Mattravers, C.; Maugain, J. M.; Maxfield, S. J.; Maximov, D. A.; May, E. N.; Mayne, A.; Mazini, R.; Mazur, M.; Mazzanti, M.; Mazzoni, E.; Mc Kee, S. P.; McCarn, A.; McCarthy, R. L.; McCarthy, T. G.; McCubbin, N. A.; McFarlane, K. W.; McFayden, J. A.; McGlone, H.; McHedlidze, G.; McLaren, R. A.; McLaughlan, T.; McMahon, S. J.; McPherson, R. A.; Meade, A.; Mechnich, J.; Mechtel, M.; Medinnis, M.; Meera-Lebbai, R.; Meguro, T.; Mehdiyev, R.; Mehlhase, S.; Mehta, A.; Meier, K.; Meinhardt, J.; Meirose, B.; Melachrinos, C.; Mellado Garcia, B. R.; Mendoza Navas, L.; Meng, Z.; Mengarelli, A.; Menke, S.; Menot, C.; Meoni, E.; Mercurio, K. M.; Mermod, P.; Merola, L.; Meroni, C.; Merritt, F. S.; Messina, A.; Metcalfe, J.; Mete, A. S.; Meuser, S.; Meyer, C.; Meyer, J.-P.; Meyer, J.; Meyer, J.; Meyer, T. C.; Meyer, W. T.; Miao, J.; Michal, S.; Micu, L.; Middleton, R. P.; Miele, P.; Migas, S.; Mijović, L.; Mikenberg, G.; Mikestikova, M.; Mikuž, M.; Miller, D. W.; Miller, R. J.; Mills, W. J.; Mills, C.; Milov, A.; Milstead, D. A.; Milstein, D.; Minaenko, A. A.; Miñano, M.; Minashvili, I. A.; Mincer, A. I.; Mindur, B.; Mineev, M.; Ming, Y.; Mir, L. M.; Mirabelli, G.; Miralles Verge, L.; Misiejuk, A.; Mitrevski, J.; Mitrofanov, G. Y.; Mitsou, V. A.; Mitsui, S.; Miyagawa, P. S.; Miyazaki, K.; Mjörnmark, J. U.; Moa, T.; Mockett, P.; Moed, S.; Moeller, V.; Mönig, K.; Möser, N.; Mohapatra, S.; Mohn, B.; Mohr, W.; Mohrdieck-Möck, S.; Moisseev, A. M.; Moles-Valls, R.; Molina-Perez, J.; Monk, J.; Monnier, E.; Montesano, S.; Monticelli, F.; Monzani, S.; Moore, R. W.; Moorhead, G. F.; Mora Herrera, C.; Moraes, A.; Morais, A.; Morange, N.; Morel, J.; Morello, G.; Moreno, D.; Moreno Llácer, M.; Morettini, P.; Morii, M.; Morin, J.; Morita, Y.; Morley, A. K.; Mornacchi, G.; Morone, M.-C.; Morozov, S. V.; Morris, J. D.; Morvaj, L.; Moser, H. G.; Mosidze, M.; Moss, J.; Mount, R.; Mountricha, E.; Mouraviev, S. V.; Moyse, E. J. W.; Mudrinic, M.; Mueller, F.; Mueller, J.; Mueller, K.; Müller, T. A.; Muenstermann, D.; Muijs, A.; Muir, A.; Munwes, Y.; Murakami, K.; Murray, W. J.; Mussche, I.; Musto, E.; Myagkov, A. G.; Myska, M.; Nadal, J.; Nagai, K.; Nagano, K.; Nagasaka, Y.; Nairz, A. M.; Nakahama, Y.; Nakamura, K.; Nakano, I.; Nanava, G.; Napier, A.; Nash, M.; Nation, N. R.; Nattermann, T.; Naumann, T.; Navarro, G.; Neal, H. A.; Nebot, E.; Nechaeva, P. Yu.; Negri, A.; Negri, G.; Nektarijevic, S.; Nelson, S.; Nelson, T. K.; Nemecek, S.; Nemethy, P.; Nepomuceno, A. A.; Nessi, M.; Nesterov, S. Y.; Neubauer, M. S.; Neusiedl, A.; Neves, R. M.; Nevski, P.; Newman, P. R.; Nguyen Thi Hong, V.; Nickerson, R. B.; Nicolaidou, R.; Nicolas, L.; Nicquevert, B.; Niedercorn, F.; Nielsen, J.; Niinikoski, T.; Nikiforov, A.; Nikolaenko, V.; Nikolaev, K.; Nikolic-Audit, I.; Nikolics, K.; Nikolopoulos, K.; Nilsen, H.; Nilsson, P.; Ninomiya, Y.; Nisati, A.; Nishiyama, T.; Nisius, R.; Nodulman, L.; Nomachi, M.; Nomidis, I.; Nordberg, M.; Nordkvist, B.; Norton, P. R.; Novakova, J.; Nozaki, M.; Nožička, M.; Nozka, L.; Nugent, I. M.; Nuncio-Quiroz, A.-E.; Nunes Hanninger, G.; Nunnemann, T.; Nurse, E.; Nyman, T.; O'Brien, B. J.; O'Neale, S. W.; O'Neil, D. C.; O'Shea, V.; Oakham, F. G.; Oberlack, H.; Ocariz, J.; Ochi, A.; Oda, S.; Odaka, S.; Odier, J.; Ogren, H.; Oh, A.; Oh, S. H.; Ohm, C. C.; Ohshima, T.; Ohshita, H.; Ohska, T. K.; Ohsugi, T.; Okada, S.; Okawa, H.; Okumura, Y.; Okuyama, T.; Olcese, M.; Olchevski, A. G.; Oliveira, M.; Oliveira Damazio, D.; Oliver Garcia, E.; Olivito, D.; Olszewski, A.; Olszowska, J.; Omachi, C.; Onofre, A.; Onyisi, P. U. E.; Oram, C. J.; Oreglia, M. J.; Oren, Y.; Orestano, D.; Orlov, I.; Oropeza Barrera, C.; Orr, R. S.; Osculati, B.; Ospanov, R.; Osuna, C.; Otero Y Garzon, G.; Ottersbach, J. P.; Ouchrif, M.; Ould-Saada, F.; Ouraou, A.; Ouyang, Q.; Owen, M.; Owen, S.; Øye, O. K.; Ozcan, V. E.; Ozturk, N.; Pacheco Pages, A.; Padilla Aranda, C.; Pagan Griso, S.; Paganis, E.; Paige, F.; Pajchel, K.; Palestini, S.; Pallin, D.; Palma, A.; Palmer, J. D.; Pan, Y. B.; Panagiotopoulou, E.; Panes, B.; Panikashvili, N.; Panitkin, S.; Pantea, D.; Panuskova, M.; Paolone, V.; Papadelis, A.; Papadopoulou, Th. D.; Paramonov, A.; Park, W.; Parker, M. A.; Parodi, F.; Parsons, J. A.; Parzefall, U.; Pasqualucci, E.; Passeri, A.; Pastore, F.; Pastore, Fr.; Pásztor, G.; Pataraia, S.; Patel, N.; Pater, J. R.; Patricelli, S.; Pauly, T.; Pecsy, M.; Pedraza Morales, M. I.; Peleganchuk, S. V.; Peng, H.; Pengo, R.; Penson, A.; Penwell, J.; Perantoni, M.; Perez, K.; Perez Cavalcanti, T.; Perez Codina, E.; Pérez García-Estañ, M. T.; Perez Reale, V.; Perini, L.; Pernegger, H.; Perrino, R.; Perrodo, P.; Persembe, S.; Peshekhonov, V. D.; Peters, K.; Peters, O.; Petersen, B. A.; Petersen, J.; Petersen, T. C.; Petit, E.; Petridis, A.; Petridou, C.; Petrolo, E.; Petrucci, F.; Petschull, D.; Petteni, M.; Pezoa, R.; Phan, A.; Phillips, A. W.; Phillips, P. W.; Piacquadio, G.; Piccaro, E.; Piccinini, M.; Pickford, A.; Piec, S. M.; Piegaia, R.; Pilcher, J. E.; Pilkington, A. D.; Pina, J.; Pinamonti, M.; Pinder, A.; Pinfold, J. L.; Ping, J.; Pinto, B.; Pirotte, O.; Pizio, C.; Placakyte, R.; Plamondon, M.; Plano, W. G.; Pleier, M.-A.; Pleskach, A. V.; Poblaguev, A.; Poddar, S.; Podlyski, F.; Poggioli, L.; Poghosyan, T.; Pohl, M.; Polci, F.; Polesello, G.; Policicchio, A.; Polini, A.; Poll, J.; Polychronakos, V.; Pomarede, D. M.; Pomeroy, D.; Pommès, K.; Pontecorvo, L.; Pope, B. G.; Popeneciu, G. A.; Popovic, D. S.; Poppleton, A.; Portell Bueso, X.; Porter, R.; Posch, C.; Pospelov, G. E.; Pospisil, S.; Potrap, I. N.; Potter, C. J.; Potter, C. T.; Poulard, G.; Poveda, J.; Prabhu, R.; Pralavorio, P.; Prasad, S.; Pravahan, R.; Prell, S.; Pretzl, K.; Pribyl, L.; Price, D.; Price, L. E.; Price, M. J.; Prichard, P. M.; Prieur, D.; Primavera, M.; Prokofiev, K.; Prokoshin, F.; Protopopescu, S.; Proudfoot, J.; Prudent, X.; Przysiezniak, H.; Psoroulas, S.; Ptacek, E.; Purdham, J.; Purohit, M.; Puzo, P.; Pylypchenko, Y.; Qian, J.; Qian, Z.; Qin, Z.; Quadt, A.; Quarrie, D. R.; Quayle, W. B.; Quinonez, F.; Raas, M.; Radescu, V.; Radics, B.; Rador, T.; Ragusa, F.; Rahal, G.; Rahimi, A. M.; Rahm, D.; Rajagopalan, S.; Rammensee, M.; Rammes, M.; Ramstedt, M.; Randrianarivony, K.; Ratoff, P. N.; Rauscher, F.; Rauter, E.; Raymond, M.; Read, A. L.; Rebuzzi, D. M.; Redelbach, A.; Redlinger, G.; Reece, R.; Reeves, K.; Reichold, A.; Reinherz-Aronis, E.; Reinsch, A.; Reisinger, I.; Reljic, D.; Rembser, C.; Ren, Z. L.; Renaud, A.; Renkel, P.; Rescigno, M.; Resconi, S.; Resende, B.; Reznicek, P.; Rezvani, R.; Richards, A.; Richter, R.; Richter-Was, E.; Ridel, M.; Rieke, S.; Rijpstra, M.; Rijssenbeek, M.; Rimoldi, A.; Rinaldi, L.; Rios, R. R.; Riu, I.; Rivoltella, G.; Rizatdinova, F.; Rizvi, E.; Robertson, S. H.; Robichaud-Veronneau, A.; Robinson, D.; Robinson, J. E. M.; Robinson, M.; Robson, A.; Rocha de Lima, J. G.; Roda, C.; Roda Dos Santos, D.; Rodier, S.; Rodriguez, D.; Roe, A.; Roe, S.; Røhne, O.; Rojo, V.; Rolli, S.; Romaniouk, A.; Romanov, V. M.; Romeo, G.; Romero Maltrana, D.; Roos, L.; Ros, E.; Rosati, S.; Rosbach, K.; Rose, M.; Rosenbaum, G. A.; Rosenberg, E. I.; Rosendahl, P. L.; Rosselet, L.; Rossetti, V.; Rossi, E.; Rossi, L. P.; Rossi, L.; Rotaru, M.; Roth, I.; Rothberg, J.; Rousseau, D.; Royon, C. R.; Rozanov, A.; Rozen, Y.; Ruan, X.; Rubinskiy, I.; Ruckert, B.; Ruckstuhl, N.; Rud, V. I.; Rudolph, C.; Rudolph, G.; Rühr, F.; Ruggieri, F.; Ruiz-Martinez, A.; Rulikowska-Zarebska, E.; Rumiantsev, V.; Rumyantsev, L.; Runge, K.; Runolfsson, O.; Rurikova, Z.; Rusakovich, N. A.; Rust, D. R.; Rutherfoord, J. P.; Ruwiedel, C.; Ruzicka, P.; Ryabov, Y. F.; Ryadovikov, V.; Ryan, P.; Rybar, M.; Rybkin, G.; Ryder, N. C.; Rzaeva, S.; Saavedra, A. F.; Sadeh, I.; Sadrozinski, H. F.-W.; Sadykov, R.; Safai Tehrani, F.; Sakamoto, H.; Salamanna, G.; Salamon, A.; Saleem, M.; Salihagic, D.; Salnikov, A.; Salt, J.; Salvachua Ferrando, B. M.; Salvatore, D.; Salvatore, F.; Salvucci, A.; Salzburger, A.; Sampsonidis, D.; Samset, B. H.; Sanchez, A.; Sandaker, H.; Sander, H. G.; Sanders, M. P.; Sandhoff, M.; Sandoval, T.; Sandstroem, R.; Sandvoss, S.; Sankey, D. P. C.; Sansoni, A.; Santamarina Rios, C.; Santoni, C.; Santonico, R.; Santos, H.; Saraiva, J. G.; Sarangi, T.; Sarkisyan-Grinbaum, E.; Sarri, F.; Sartisohn, G.; Sasaki, O.; Sasaki, T.; Sasao, N.; Satsounkevitch, I.; Sauvage, G.; Sauvan, E.; Sauvan, J. B.; Savard, P.; Savinov, V.; Savu, D. O.; Savva, P.; Sawyer, L.; Saxon, D. H.; Says, L. P.; Sbarra, C.; Sbrizzi, A.; Scallon, O.; Scannicchio, D. A.; Schaarschmidt, J.; Schacht, P.; Schäfer, U.; Schaepe, S.; Schaetzel, S.; Schaffer, A. C.; Schaile, D.; Schamberger, R. D.; Schamov, A. G.; Scharf, V.; Schegelsky, V. A.; Scheirich, D.; Schernau, M.; Scherzer, M. I.; Schiavi, C.; Schieck, J.; Schioppa, M.; Schlenker, S.; Schlereth, J. L.; Schmidt, E.; Schmieden, K.; Schmitt, C.; Schmitt, S.; Schmitz, M.; Schöning, A.; Schott, M.; Schouten, D.; Schovancova, J.; Schram, M.; Schroeder, C.; Schroer, N.; Schuh, S.; Schuler, G.; Schultes, J.; Schultz-Coulon, H.-C.; Schulz, H.; Schumacher, J. W.; Schumacher, M.; Schumm, B. A.; Schune, Ph.; Schwanenberger, C.; Schwartzman, A.; Schwemling, Ph.; Schwienhorst, R.; Schwierz, R.; Schwindling, J.; Schwindt, T.; Scott, W. G.; Searcy, J.; Sedykh, E.; Segura, E.; Seidel, S. C.; Seiden, A.; Seifert, F.; Seixas, J. M.; Sekhniaidze, G.; Seliverstov, D. M.; Sellden, B.; Sellers, G.; Seman, M.; Semprini-Cesari, N.; Serfon, C.; Serin, L.; Seuster, R.; Severini, H.; Sevior, M. E.; Sfyrla, A.; Shabalina, E.; Shamim, M.; Shan, L. Y.; Shank, J. T.; Shao, Q. T.; Shapiro, M.; Shatalov, P. B.; Shaver, L.; Shaw, C.; Shaw, K.; Sherman, D.; Sherwood, P.; Shibata, A.; Shichi, H.; Shimizu, S.; Shimojima, M.; Shin, T.; Shmeleva, A.; Shochet, M. J.; Short, D.; Shupe, M. A.; Sicho, P.; Sidoti, A.; Siebel, A.; Siegert, F.; Siegrist, J.; Sijacki, Dj.; Silbert, O.; Silva, J.; Silver, Y.; Silverstein, D.; Silverstein, S. B.; Simak, V.; Simard, O.; Simic, Lj.; Simion, S.; Simmons, B.; Simonyan, M.; Sinervo, P.; Sinev, N. B.; Sipica, V.; Siragusa, G.; Sisakyan, A. N.; Sivoklokov, S. Yu.; Sjölin, J.; Sjursen, T. B.; Skinnari, L. A.; Skovpen, K.; Skubic, P.; Skvorodnev, N.; Slater, M.; Slavicek, T.; Sliwa, K.; Sloan, T. J.; Sloper, J.; Smakhtin, V.; Smirnov, S. Yu.; Smirnova, L. N.; Smirnova, O.; Smith, B. C.; Smith, D.; Smith, K. M.; Smizanska, M.; Smolek, K.; Snesarev, A. A.; Snow, S. W.; Snow, J.; Snuverink, J.; Snyder, S.; Soares, M.; Sobie, R.; Sodomka, J.; Soffer, A.; Solans, C. A.; Solar, M.; Solc, J.; Soldatov, E.; Soldevila, U.; Solfaroli Camillocci, E.; Solodkov, A. A.; Solovyanov, O. V.; Sondericker, J.; Soni, N.; Sopko, V.; Sopko, B.; Sorbi, M.; Sosebee, M.; Soukharev, A.; Spagnolo, S.; Spanò, F.; Spighi, R.; Spigo, G.; Spila, F.; Spiriti, E.; Spiwoks, R.; Spousta, M.; Spreitzer, T.; Spurlock, B.; St. Denis, R. D.; Stahl, T.; Stahlman, J.; Stamen, R.; Stanecka, E.; Stanek, R. W.; Stanescu, C.; Stapnes, S.; Starchenko, E. A.; Stark, J.; Staroba, P.; Starovoitov, P.; Staude, A.; Stavina, P.; Stavropoulos, G.; Steele, G.; Steinbach, P.; Steinberg, P.; Stekl, I.; Stelzer, B.; Stelzer, H. J.; Stelzer-Chilton, O.; Stenzel, H.; Stevenson, K.; Stewart, G. A.; Stillings, J. A.; Stockmanns, T.; Stockton, M. C.; Stoerig, K.; Stoicea, G.; Stonjek, S.; Strachota, P.; Stradling, A. R.; Straessner, A.; Strandberg, J.; Strandberg, S.; Strandlie, A.; Strang, M.; Strauss, E.; Strauss, M.; Strizenec, P.; Ströhmer, R.; Strom, D. M.; Strong, J. A.; Stroynowski, R.; Strube, J.; Stugu, B.; Stumer, I.; Stupak, J.; Sturm, P.; Soh, D. A.; Su, D.; Subramania, Hs.; Succurro, A.; Sugaya, Y.; Sugimoto, T.; Suhr, C.; Suita, K.; Suk, M.; Sulin, V. V.; Sultansoy, S.; Sumida, T.; Sun, X.; Sundermann, J. E.; Suruliz, K.; Sushkov, S.; Susinno, G.; Sutton, M. R.; Suzuki, Y.; Svatos, M.; Sviridov, Yu. M.; Swedish, S.; Sykora, I.; Sykora, T.; Szeless, B.; Sánchez, J.; Ta, D.; Tackmann, K.; Taffard, A.; Tafirout, R.; Taga, A.; Taiblum, N.; Takahashi, Y.; Takai, H.; Takashima, R.; Takeda, H.; Takeshita, T.; Talby, M.; Talyshev, A.; Tamsett, M. C.; Tanaka, J.; Tanaka, R.; Tanaka, S.; Tanaka, S.; Tanaka, Y.; Tani, K.; Tannoury, N.; Tappern, G. P.; Tapprogge, S.; Tardif, D.; Tarem, S.; Tarrade, F.; Tartarelli, G. F.; Tas, P.; Tasevsky, M.; Tassi, E.; Tatarkhanov, M.; Taylor, C.; Taylor, F. E.; Taylor, G. N.; Taylor, W.; Teixeira Dias Castanheira, M.; Teixeira-Dias, P.; Temming, K. K.; Ten Kate, H.; Teng, P. K.; Terada, S.; Terashi, K.; Terron, J.; Terwort, M.; Testa, M.; Teuscher, R. J.; Thadome, J.; Therhaag, J.; Theveneaux-Pelzer, T.; Thioye, M.; Thoma, S.; Thomas, J. P.; Thompson, E. N.; Thompson, P. D.; Thompson, P. D.; Thompson, A. S.; Thomson, E.; Thomson, M.; Thun, R. P.; Tic, T.; Tikhomirov, V. O.; Tikhonov, Y. A.; Timmermans, C. J. W. P.; Tipton, P.; Tique Aires Viegas, F. J.; Tisserant, S.; Tobias, J.; Toczek, B.; Todorov, T.; Todorova-Nova, S.; Toggerson, B.; Tojo, J.; Tokár, S.; Tokunaga, K.; Tokushuku, K.; Tollefson, K.; Tomoto, M.; Tompkins, L.; Toms, K.; Tong, G.; Tonoyan, A.; Topfel, C.; Topilin, N. D.; Torchiani, I.; Torrence, E.; Torres, H.; Torró Pastor, E.; Toth, J.; Touchard, F.; Tovey, D. R.; Traynor, D.; Trefzger, T.; Tremblet, L.; Tricoli, A.; Trigger, I. M.; Trincaz-Duvoid, S.; Trinh, T. N.; Tripiana, M. F.; Trischuk, W.; Trivedi, A.; Trocmé, B.; Troncon, C.; Trottier-McDonald, M.; Trzupek, A.; Tsarouchas, C.; Tseng, J. C.-L.; Tsiakiris, M.; Tsiareshka, P. V.; Tsionou, D.; Tsipolitis, G.; Tsiskaridze, V.; Tskhadadze, E. G.; Tsukerman, I. I.; Tsulaia, V.; Tsung, J.-W.; Tsuno, S.; Tsybychev, D.; Tua, A.; Tuggle, J. M.; Turala, M.; Turecek, D.; Turk Cakir, I.; Turlay, E.; Turra, R.; Tuts, P. M.; Tykhonov, A.; Tylmad, M.; Tyndel, M.; Tyrvainen, H.; Tzanakos, G.; Uchida, K.; Ueda, I.; Ueno, R.; Ugland, M.; Uhlenbrock, M.; Uhrmacher, M.; Ukegawa, F.; Unal, G.; Underwood, D. G.; Undrus, A.; Unel, G.; Unno, Y.; Urbaniec, D.; Urkovsky, E.; Urrejola, P.; Usai, G.; Uslenghi, M.; Vacavant, L.; Vacek, V.; Vachon, B.; Vahsen, S.; Valenta, J.; Valente, P.; Valentinetti, S.; Valkar, S.; Valladolid Gallego, E.; Vallecorsa, S.; Valls Ferrer, J. A.; van der Graaf, H.; van der Kraaij, E.; van der Leeuw, R.; van der Poel, E.; van der Ster, D.; van Eijk, B.; van Eldik, N.; van Gemmeren, P.; van Kesteren, Z.; van Vulpen, I.; Vandelli, W.; Vandoni, G.; Vaniachine, A.; Vankov, P.; Vannucci, F.; Varela Rodriguez, F.; Vari, R.; Varnes, E. W.; Varouchas, D.; Vartapetian, A.; Varvell, K. E.; Vassilakopoulos, V. I.; Vazeille, F.; Vegni, G.; Veillet, J. J.; Vellidis, C.; Veloso, F.; Veness, R.; Veneziano, S.; Ventura, A.; Ventura, D.; Venturi, M.; Venturi, N.; Vercesi, V.; Verducci, M.; Verkerke, W.; Vermeulen, J. C.; Vest, A.; Vetterli, M. C.; Vichou, I.; Vickey, T.; Viehhauser, G. H. A.; Viel, S.; Villa, M.; Villaplana Perez, M.; Vilucchi, E.; Vincter, M. G.; Vinek, E.; Vinogradov, V. B.; Virchaux, M.; Virzi, J.; Vitells, O.; Viti, M.; Vivarelli, I.; Vives Vaque, F.; Vlachos, S.; Vlasak, M.; Vlasov, N.; Vogel, A.; Vokac, P.; Volpi, G.; Volpi, M.; Volpini, G.; von der Schmitt, H.; von Loeben, J.; von Radziewski, H.; von Toerne, E.; Vorobel, V.; Vorobiev, A. P.; Vorwerk, V.; Vos, M.; Voss, R.; Voss, T. T.; Vossebeld, J. H.; Vranjes, N.; Vranjes Milosavljevic, M.; Vrba, V.; Vreeswijk, M.; Vu Anh, T.; Vuillermet, R.; Vukotic, I.; Wagner, W.; Wagner, P.; Wahlen, H.; Wakabayashi, J.; Walbersloh, J.; Walch, S.; Walder, J.; Walker, R.; Walkowiak, W.; Wall, R.; Waller, P.; Wang, C.; Wang, H.; Wang, H.; Wang, J.; Wang, J.; Wang, J. C.; Wang, R.; Wang, S. M.; Warburton, A.; Ward, C. P.; Warsinsky, M.; Watkins, P. M.; Watson, A. T.; Watson, M. F.; Watts, G.; Watts, S.; Waugh, A. T.; Waugh, B. M.; Weber, J.; Weber, M.; Weber, M. S.; Weber, P.; Weidberg, A. R.; Weigell, P.; Weingarten, J.; Weiser, C.; Wellenstein, H.; Wells, P. S.; Wen, M.; Wenaus, T.; Wendler, S.; Weng, Z.; Wengler, T.; Wenig, S.; Wermes, N.; Werner, M.; Werner, P.; Werth, M.; Wessels, M.; Weydert, C.; Whalen, K.; Wheeler-Ellis, S. J.; Whitaker, S. P.; White, A.; White, M. J.; White, S.; Whitehead, S. R.; Whiteson, D.; Whittington, D.; Wicek, F.; Wicke, D.; Wickens, F. J.; Wiedenmann, W.; Wielers, M.; Wienemann, P.; Wiglesworth, C.; Wiik, L. A. M.; Wijeratne, P. A.; Wildauer, A.; Wildt, M. A.; Wilhelm, I.; Wilkens, H. G.; Will, J. Z.; Williams, E.; Williams, H. H.; Willis, W.; Willocq, S.; Wilson, J. A.; Wilson, M. G.; Wilson, A.; Wingerter-Seez, I.; Winkelmann, S.; Winklmeier, F.; Wittgen, M.; Wolter, M. W.; Wolters, H.; Wooden, G.; Wosiek, B. K.; Wotschack, J.; Woudstra, M. J.; Wraight, K.; Wright, C.; Wrona, B.; Wu, S. L.; Wu, X.; Wu, Y.; Wulf, E.; Wunstorf, R.; Wynne, B. M.; Xaplanteris, L.; Xella, S.; Xie, S.; Xie, Y.; Xu, C.; Xu, D.; Xu, G.; Yabsley, B.; Yamada, M.; Yamamoto, A.; Yamamoto, K.; Yamamoto, S.; Yamamura, T.; Yamaoka, J.; Yamazaki, T.; Yamazaki, Y.; Yan, Z.; Yang, H.; Yang, U. K.; Yang, Y.; Yang, Y.; Yang, Z.; Yanush, S.; Yao, W.-M.; Yao, Y.; Yasu, Y.; Ybeles Smit, G. V.; Ye, J.; Ye, S.; Yilmaz, M.; Yoosoofmiya, R.; Yorita, K.; Yoshida, R.; Young, C.; Youssef, S.; Yu, D.; Yu, J.; Yu, J.; Yuan, L.; Yurkewicz, A.; Zaets, V. G.; Zaidan, R.; Zaitsev, A. M.; Zajacova, Z.; Zalite, Yo. K.; Zanello, L.; Zarzhitsky, P.; Zaytsev, A.; Zeitnitz, C.; Zeller, M.; Zemla, A.; Zendler, C.; Zenin, A. V.; Zenin, O.; Ženiš, T.; Zenonos, Z.; Zenz, S.; Zerwas, D.; Zevi Della Porta, G.; Zhan, Z.; Zhang, D.; Zhang, H.; Zhang, J.; Zhang, X.; Zhang, Z.; Zhao, L.; Zhao, T.; Zhao, Z.; Zhemchugov, A.; Zheng, S.; Zhong, J.; Zhou, B.; Zhou, N.; Zhou, Y.; Zhu, C. G.; Zhu, H.; Zhu, J.; Zhu, Y.; Zhuang, X.; Zhuravlov, V.; Zieminska, D.; Zimmermann, R.; Zimmermann, S.; Zimmermann, S.; Ziolkowski, M.; Zitoun, R.; Živković, L.; Zmouchko, V. V.; Zobernig, G.; Zoccoli, A.; Zolnierowski, Y.; Zsenei, A.; Zur Nedden, M.; Zutshi, V.; Zwalinski, L.

2012-01-01

The ATLAS experiment has measured the production cross section of events with two isolated photons in the final state, in proton-proton collisions at s=7TeV. The full data set acquired in 2010 is used, corresponding to an integrated luminosity of 37pb-1. The background, consisting of hadronic jets and isolated electrons, is estimated with fully data-driven techniques and subtracted. The differential cross sections, as functions of the di-photon mass (mγγ), total transverse momentum (pT,γγ), and azimuthal separation (Δϕγγ), are presented and compared to the predictions of next-to-leading-order QCD.

Proton acceleration by a pair of successive ultraintense femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Ferri, J.; Senje, L.; Dalui, M.; Svensson, K.; Aurand, B.; Hansson, M.; Persson, A.; Lundh, O.; Wahlström, C.-G.; Gremillet, L.; Siminos, E.; DuBois, T. C.; Yi, L.; Martins, J. L.; Fülöp, T.

2018-04-01

We investigate the target normal sheath acceleration of protons in thin aluminum targets irradiated at a relativistic intensity by two time-separated ultrashort (35 fs) laser pulses. When the full-energy laser pulse is temporally split into two identical half-energy pulses, and using target thicknesses of 3 and 6 μm, we observe experimentally that the second half-pulse boosts the maximum energy and charge of the proton beam produced by the first half-pulse for time delays below ˜0.6-1 ps. Using two-dimensional particle-in-cell simulations, we examine the variation of the proton energy spectra with respect to the time-delay between the two pulses. We demonstrate that the expansion of the target front surface caused by the first pulse significantly enhances the hot-electron generation by the second pulse arriving after a few hundreds of fs time delay. This enhancement, however, does not suffice to further accelerate the fastest protons driven by the first pulse once three-dimensional quenching effects have set in. This implies a limit to the maximum time delay that leads to proton energy enhancement, which we theoretically determine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deisenhofer, J.; Michel, H.

The history and methods of membrane protein crystallization are described. The solution of the structure of the photosynthetic reaction center from the bacterium Rhodopseudomonas viridis is described, and the structure of this membrane protein complex is correlated with its function as a light-driven electron pump across the photosynthetic membrane. Conclusions about the structure of the photosystem II reaction center from plants are drawn, and aspects of membrane protein structure are discussed. 68 refs., 15 figs., 2 tabs.

Comparison of p.o. or i.v. proton pump inhibitors on 72-h intragastric pH in bleeding peptic ulcer.

PubMed

Javid, Gul; Zargar, Showkat Ali; U-Saif, Riyaz-; Khan, Bashir Ahmad; Yatoo, Ghulam Nabi; Shah, Altaf Hussain; Gulzar, Ghulam Mohammad; Sodhi, Jaswinder Singh; Khan, Mushtaq Ahmad

2009-07-01

After successful endoscopic hemostasis in bleeding peptic ulcer, addition of proton pump inhibitors reduce the rate of recurrent bleeding by maintaining intragastric pH at neutral level. The aim of the present study was to evaluate the effect of various proton pump inhibitors given through different routes on intragastric pH over 72 h after endoscopic hemostasis in bleeding peptic ulcer. Ninety consecutive patients who had successful endoscopic therapy of bleeding peptic ulcer underwent 72-h continuous ambulatory intragastric pH study, were randomly assigned to receive p.o. omeprazole 80 mg bolus followed by 40 mg every 12 h for 72 h or i.v. 80 mg omeprazole followed by infusion 8 mg/h for 72 h. Oral pantoprazole 80 mg bolus followed by 80 mg every 12 h for 72 h or i.v. 80 mg pantoprazole followed by infusion of 8 mg/h for 72 h. Oral rabeprazole 80 mg bolus followed by 40 mg every 12 h for 72 h or i.v. 80 mg rabeprazole followed by infusion 8 mg/h for 72 h. Five patients received no treatment after successful endoscopic therapy and underwent 72-h pH study. Mean 72-h intragastric pH for p.o. omeprazole was 6.56 versus 6.93 for omeprazole infusion (P = 0.48). Mean 72-h intragastric pH for p.o. pantoprazole was 6.34 versus 6.32 for pantoprazole infusion (P = 0.62). Mean 72-h intragastric pH for rabeprazole p.o. was 6.11 versus 6.18 rabeprazole i.v. (P = 0.55). Mean 72-h pH for the no proton pump inhibitor group was 2.04. There was no significant difference among various proton pump inhibitors given through different routes on raising intragastric pH above 6 for 72 h after successful endoscopic hemostasis in bleeding peptic ulcer.

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

NASA Astrophysics Data System (ADS)

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.

Recent Observations and Modeling of Narrowband Stimulated Electromagnetic Emissions SEEs at the HAARP Facility

NASA Astrophysics Data System (ADS)

Scales, Wayne; Bernhardt, Paul; McCarrick, Michael; Briczinski, Stanley; Mahmoudian, Alireza; Fu, Haiyang; Ranade Bordikar, Maitrayee; Samimi, Alireza

There has been significant interest in so-called narrowband Stimulated Electromagnetic Emission SEE over the past several years due to recent discoveries at the High Frequency Active Auroral Research Program HAARP facility near Gakone, Alaska. Narrowband SEE (NSEE) has been defined as spectral features in the SEE spectrum typically within 1 kHz of the transmitter (or pump) frequency. SEE is due to nonlinear processes leading to re-radiation at frequencies other than the pump wave frequency during heating the ionospheric plasma with high power HF radio waves. Although NSEE exhibits a richly complex structure, it has now been shown after a substantial number of observations at HAARP, that NSEE can be grouped into two basic classes. The first are those spectral features, associated with Stimulated Brillouin Scatter SBS, which typically occur when the pump frequency is not close to electron gyro-harmonic frequencies. Typically, these spectral features are within roughly 50 Hz of the pump wave frequency where it is to be noted that the O+ ion gyro-frequency is roughly 50 Hz. The second class of spectral features corresponds to the case when the pump wave frequency is typically within roughly 10 kHz of electron gyro-harmonic frequencies. In this case, spectral features ordered by harmonics of ion gyro-frequencies are typically observed, and termed Stimulated Ion Bernstein Scatter SIBS. There is also important parametric behavior on both classes of NSEE depending on the pump wave parameters including the field strength, antenna beam angle, and electron gyro-harmonic number. This presentation will first provide an overview of the recent NSEE experimental observations at HAARP. Both Stimulated Brillouin Scatter SBS and Stimulated Ion Bernstein Scatter SIBS observations will be discussed as well as their relationship to each other. Possible theoretical formulation in terms of parametric decay instabilities will be provided. Computer simulation model results will be presented to provide insight into associated higher order nonlinear effects including particle acceleration and wave-wave processes. Both theory and model results will be put into the context of the experimental observations. Finally, possible applications of NSEE will be pointed out including triggering diagnostics for artificial ionization layer formation, proton precipitation event diagnostics, and electron temperature measurements in the heated volume.

An analytical study of hybrid ejector/internal combustion engine-driven heat pumps

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murphy, R.W.

1988-01-01

Because ejectors can combine high reliability with low maintenance cost in a package requiring little capital investment, they may provide attractive heat pumping capability in situations where the importance of their inefficiencies is minimized. One such concept, a hybrid system in which an ejector driven by engine reject heat is used to increase the performance of an internal combustion engine-driven heat pump, was analyzed by modifying an existing ejector heat pump model and combining it with generic compressor and internal combustion engine models. Under the model assumptions for nominal cooling mode conditions, the results showed that hybrid systems could providemore » substantial performance augmentation/emdash/up to 17/percent/ increase in system coefficient of performance for a parallel arrangement of an enhanced ejector with the engine-driven compressor. 4 refs., 4 figs., 4 tabs.« less

HOW MAY PROTON PUMP INHIBITORS IMPAIR CARDIOVASCULAR HEALTH?

PubMed Central

Sukhovershin, Roman A.; Cooke, John P.

2016-01-01

Proton pump inhibitors (PPIs) are among the most widely used drugs worldwide. They are used to treat a number of gastro-esophageal disorders and usually prescribed as a long-term medication or even taken without a prescription. There are a number of clinical studies that associate PPI use with an increased cardiovascular risk. In this article we review the clinical evidence for adverse cardiovascular effects of PPIs, and we discuss possible biological mechanisms by which PPIs can impair cardiovascular health. PMID:26817947

Effects of Helicobacter pylori infection and long-term proton pump inhibitor use on enterochromaffin-like cells.

PubMed

Bektaş, Mehmet; Saraç, Nurşen; Cetinkaya, Hülya; Törüner, Murat; Erdemli, Esra; Keskin, Onur; Soykan, Irfan; Oktay, Esen Ismet; Korkut, Esin; Ustün, Yusuf; Bahar, Kadir

2012-01-01

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. 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. 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. The use of PPI for a long period of time and presence of H. pylori infection are risk factors for ECL hyperplasia.

Model Construction and Analysis of Respiration in Halobacterium salinarum.

PubMed

Talaue, Cherryl O; del Rosario, Ricardo C H; Pfeiffer, Friedhelm; Mendoza, Eduardo R; Oesterhelt, Dieter

2016-01-01

The archaeon Halobacterium salinarum can produce energy using three different processes, namely photosynthesis, oxidative phosphorylation and fermentation of arginine, and is thus a model organism in bioenergetics. Compared to its bacteriorhodopsin-driven photosynthesis, less attention has been devoted to modeling its respiratory pathway. We created a system of ordinary differential equations that models its oxidative phosphorylation. The model consists of the electron transport chain, the ATP synthase, the potassium uniport and the sodium-proton antiport. By fitting the model parameters to experimental data, we show that the model can explain data on proton motive force generation, ATP production, and the charge balancing of ions between the sodium-proton antiporter and the potassium uniport. We performed sensitivity analysis of the model parameters to determine how the model will respond to perturbations in parameter values. The model and the parameters we derived provide a resource that can be used for analytical studies of the bioenergetics of H. salinarum.

Laser-driven collimated tens-GeV monoenergetic protons from mass-limited target plus preformed channel

NASA Astrophysics Data System (ADS)

Zheng, F. L.; Wu, S. Z.; Wu, H. C.; Zhou, C. T.; Cai, H. B.; Yu, M. Y.; Tajima, T.; Yan, X. Q.; He, X. T.

2013-01-01

Proton acceleration by ultra-intense laser pulse irradiating a target with cross-section smaller than the laser spot size and connected to a parabolic density channel is investigated. The target splits the laser into two parallel propagating parts, which snowplow the back-side plasma electrons along their paths, creating two adjacent parallel wakes and an intense return current in the gap between them. The radiation-pressure pre-accelerated target protons trapped in the wake fields now undergo acceleration as well as collimation by the quasistatic wake electrostatic and magnetic fields. Particle-in-cell simulations show that stable long-distance acceleration can be realized, and a 30 fs monoenergetic ion beam of >10 GeV peak energy and <2° divergence can be produced by a circularly polarized laser pulse at an intensity of about 1022 W/cm2.

Structure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM.

PubMed

Zhou, Anna; Rohou, Alexis; Schep, Daniel G; Bason, John V; Montgomery, Martin G; Walker, John E; Grigorieff, Nikolaus; Rubinstein, John L

2015-10-06

Adenosine triphosphate (ATP), the chemical energy currency of biology, is synthesized in eukaryotic cells primarily by the mitochondrial ATP synthase. ATP synthases operate by a rotary catalytic mechanism where proton translocation through the membrane-inserted FO region is coupled to ATP synthesis in the catalytic F1 region via rotation of a central rotor subcomplex. We report here single particle electron cryomicroscopy (cryo-EM) analysis of the bovine mitochondrial ATP synthase. Combining cryo-EM data with bioinformatic analysis allowed us to determine the fold of the a subunit, suggesting a proton translocation path through the FO region that involves both the a and b subunits. 3D classification of images revealed seven distinct states of the enzyme that show different modes of bending and twisting in the intact ATP synthase. Rotational fluctuations of the c8-ring within the FO region support a Brownian ratchet mechanism for proton-translocation-driven rotation in ATP synthases.

RF-driven ion source with a back-streaming electron dump

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwan, Joe; Ji, Qing

A novel ion source is described having an improved lifetime. The ion source, in one embodiment, is a proton source, including an external RF antenna mounted to an RF window. To prevent backstreaming electrons formed in the beam column from striking the RF window, a back streaming electron dump is provided, which in one embodiment is formed of a cylindrical tube, open at one end to the ion source chamber and capped at its other end by a metal plug. The plug, maintained at the same electrical potential as the source, captures these backstreaming electrons, and thus prevents localized heatingmore » of the window, which due to said heating, might otherwise cause window damage.« less

Characterization of an induced pressure pumping force for microfluidics

NASA Astrophysics Data System (ADS)

Jiang, Hai; Fan, Na; Peng, Bei; Weng, Xuan

2017-05-01

The electro-osmotic pumping and pressure-driven manipulation of fluids are considered as the most common strategies in microfluidic devices. However, both of them exhibit major disadvantages such as hard integration and high reagent consumption, and they are destructive methods for detection and photo bleaching. In this paper, an electric field-effect flow control approach, combining the electro-osmotic pumping force and the pressure-driven pumping force, was developed to generate the induced pressure-driven flow in a T-shaped microfluidic chip. Electro-osmotic flow between the T-intersection and two reservoirs was demonstrated, and it provided a stable, continuous, and electric field-free flow in the section of the microchannel without the electrodes. The velocity of the induced pressure-driven flow was linearly proportional to the applied voltages. Both numerical and experimental investigations were conducted to prove the concept, and the experimental results showed good agreement with the numerical simulations. In comparison to other induced pressure pumping methods, this approach can induce a high and controllable pressure drop in the electric field-free segment, subsequently causing an induced pressure-driven flow for transporting particles or biological cells. In addition, the generation of bubbles and the blocking of the microchannel are avoided.

Attosecond Spectroscopy Probing Electron Correlation Dynamics

NASA Astrophysics Data System (ADS)

Winney, Alexander H.

Electrons are the driving force behind every chemical reaction. The exchange, ionization, or even relaxation of electrons is behind every bond broken or formed. According to the Bohr model of the atom, it takes an electron 150 as to orbit a proton[6]. With this as a unit time scale for an electron, it is clear that a pulse duration of several femtoseconds will not be sufficient to understanding electron dynamics. Our work demonstrates both technical and scientific achievements that push the boundaries of attosecond dynamics. TDSE studies show that amplification the yield of high harmonic generation (HHG) may be possible with transverse confinement of the electron. XUV-pump-XUV-probe shows that the yield of APT train can be sufficient for 2-photon double ionization studies. A zero dead-time detection system allows for the measurement of state-resolved double ionization for the first time. Exploiting attosecond angular streaking[7] probes sequential and non-sequential double ionization via electron-electron correlations with attosecond time resolution. Finally, using recoil frame momentum correlation, the fast dissociation of CH 3I reveals important orbital ionization dynamics of non-dissociative & dissociative, single & double ionization.

Parametric interaction and spatial collapse of beam-driven Langmuir waves in the solar wind. [upstream of Jupiter bow shock

NASA Technical Reports Server (NTRS)

Gurnett, D. A.; Maggs, J. E.; Gallagher, D. L.; Kurth, W. S.; Scarf, F. L.

1981-01-01

Observations are presented of the parametric decay and spatial collapse of Langmuir waves driven by an electron beam streaming into the solar wind from the Jovian bow shock. Long wavelength Langmuir waves upstream of the bow shock are effectively converted into short wavelength waves no longer in resonance with the beam. The conversion is shown to be the result of a nonlinear interaction involving the beam-driven pump, a sideband emission, and a low level of ion-acoustic turbulence. The beam-driven Langmuir wave emission breaks up into a complex sideband structure with both positive and negative Doppler shifts. In some cases, the sideband emission consists of isolated wave packets with very short duration bursts, which are very intense and are thought to consist of envelope solitons which have collapsed to spatial scales of only a few Debye lengths.

Emitron: microwave diode

DOEpatents

Craig, G.D.; Pettibone, J.S.; Drobot, A.T.

1982-05-06

The invention comprises a new class of device, driven by electron or other charged particle flow, for producing coherent microwaves by utilizing the interaction of electromagnetic waves with electron flow in diodes not requiring an external magnetic field. Anode and cathode surfaces are electrically charged with respect to one another by electron flow, for example caused by a Marx bank voltage source or by other charged particle flow, for example by a high energy charged particle beam. This produces an electric field which stimulates an emitted electron beam to flow in the anode-cathode region. The emitted electrons are accelerated by the electric field and coherent microwaves are produced by the three dimensional spatial and temporal interaction of the accelerated electrons with geometrically allowed microwave modes which results in the bunching of the electrons and the pumping of at least one dominant microwave mode.

Ultrafast Study of Dynamic Exchange Coupling in Ferromagnet/Oxide/Semiconductor Heterostructures

NASA Astrophysics Data System (ADS)

Ou, Yu-Sheng

Spintronics is the area of research that aims at utilizing the quantum mechanical spin degree of freedom of electrons in solid-state materials for information processing and data storage application. Since the discovery of the giant magnetoresistance, the field of spintronics has attracted lots of attention for its numerous potential advantages over contemporary electronics, such as less power consumption, high integration density and non-volatility. The realization of a spin battery, defined by the ability to create spin current without associated charge current, has been a long-standing goal in the field of spintronics. The demonstration of pure spin current in ferromagnet/nonmagnetic material hybrid structures by ferromagnetic resonance spin pumping has defined a thrilling direction for this field. As such, this dissertation targets at exploring the spin and magnetization dynamics in ferromagnet/oxide/semiconductor heterostructures (Fe/MgO/GaAs) using time-resolved optical pump-probe spectroscopy with the long-range goal of understanding the fundamentals of FMR-driven spin pumping. Fe/GaAs heterostructures are complex systems that contain multiple spin species, including paramagnetic spins (GaAs electrons), nuclear spins (Ga and As nuclei) and ferromagnetic spins (Fe). Optical pump-probe studies on their interplay have revealed a number of novel phenomena that has not been explored before. As such they will be the major focus of this dissertation. First, I will discuss the effect of interfacial exchange coupling on the GaAs free-carrier spin relaxation. Temperature- and field-dependent spin-resolved pump-probe studies reveal a strong correlation of the electron spin relaxation with carrier freeze-out, in quantitative agreement with a theoretical interpretation that at low temperatures the free-carrier spin lifetime is dominated by inhomogeneity in the local hyperfine field due to carrier localization. Second, we investigate the impact of tunnel barrier thickness on GaAs electron spin dynamics in Fe/MgO/GaAs heterostructures. Comparison of the Larmor frequency between samples with thick and thin MgO barriers reveals a four-fold variation in exchange coupling strength, and investigation of the spin lifetimes argues that inhomogeneity in the local hyperfine field dominates free-carrier spin relaxation across the entire range of barrier thickness. These results provide additional evidence to support the theory of hyperfine-dominated spin relaxation in GaAs. Third, we investigated the origin and dynamics of an emergent spin population by pump power and magnetic field dependent spin-resolved pump-probe studies. Power dependent study confirms its origin to be filling of electronic states in GaAs, and further field dependent studies reveal the impact of contact hyperfine coupling on the dynamics of electron spins occupying distinct electronic states. Beyond above works, we also pursue optical detection of dynamic spin pumping in Fe/MgO/GaAs heterostructures in parallel. I will discuss the development and progress that we have made toward this goal. This project can be simply divided into two phases. In the first phase, we focused on microwave excitation and optical detection of spin pumping. In the second phase, we focused on all-optical excitation and detection of spin pumping. A number of measurement strategies have been developed and executed in both stages to hunt for a spin pumping signal. I will discuss the preliminary data based upon them.

Experimental implementation of a biometric laser synaptic sensor.

PubMed

Pisarchik, Alexander N; Sevilla-Escoboza, Ricardo; Jaimes-Reátegui, Rider; Huerta-Cuellar, Guillermo; García-Lopez, J Hugo; Kazantsev, Victor B

2013-12-16

We fabricate a biometric laser fiber synaptic sensor to transmit information from one neuron cell to the other by an optical way. The optical synapse is constructed on the base of an erbium-doped fiber laser, whose pumped diode current is driven by a pre-synaptic FitzHugh-Nagumo electronic neuron, and the laser output controls a post-synaptic FitzHugh-Nagumo electronic neuron. The implemented laser synapse displays very rich dynamics, including fixed points, periodic orbits with different frequency-locking ratios and chaos. These regimes can be beneficial for efficient biorobotics, where behavioral flexibility subserved by synaptic connectivity is a challenge.

Parametric decay of current-driven Langmuir oscillations and wave packet formation in plateau plasmas: Relevance to type III bursts

NASA Astrophysics Data System (ADS)

Sauer, K.; Malaspina, D.; Pulupa, M.

2016-12-01

Instead of starting with an unstable electron beam, our focus is directed on the nonlinear response of Langmuir oscillations which are driven after beam stabilization by the still persisting current of the (stable) two-electron plasma. The velocity distribution function of the second population forms a plateau with weak damping over a more or less extended wave number range k. As shown by PIC simulations, this so-called plateau plasma drives primarily Langmuir oscillations at the plasma frequency ωe with k=0 over long times without remarkable change of the distribution function. The Langmuir oscillations, however, act as pump wave for parametric decay by which an electron-acoustic wave slightly below ωe and a counter-streaming ion-acoustic wave are generated. Both high-frequency waves have nearly the same amplitude which is simply given by the product of plateau density and velocity. Beating of these two wave types leads to pronounced Langmuir amplitude modulation, in good agreement with solar wind and foreshock WIND observations where waveforms and electron distribution functions have simultaneously been analyzed.

How cytochrome c oxidase can pump four protons per oxygen molecule at high electrochemical gradient.

PubMed

Blomberg, Margareta R A; Siegbahn, Per E M

2015-03-01

Experiments have shown that the A-family cytochrome c oxidases pump four protons per oxygen molecule, also at a high electrochemical gradient. This has been considered a puzzle, since two of the reduction potentials involved, Cu(II) and Fe(III), were estimated from experiments to be too low to afford proton pumping at a high gradient. The present quantum mechanical study (using hybrid density functional theory) suggests a solution to this puzzle. First, the calculations show that the charge compensated Cu(II) potential for CuB is actually much higher than estimated from experiment, of the same order as the reduction potentials for the tyrosyl radical and the ferryl group, which are also involved in the catalytic cycle. The reason for the discrepancy between theory and experiment is the very large uncertainty in the experimental observations used to estimate the equilibrium potentials, mainly caused by the lack of methods for direct determination of reduced CuB. Second, the calculations show that a high energy metastable state, labeled EH, is involved during catalytic turnover. The EH state mixes the low reduction potential of Fe(III) in heme a3 with another, higher potential, here suggested to be that of the tyrosyl radical, resulting in enough exergonicity to allow proton pumping at a high gradient. In contrast, the corresponding metastable oxidized state, OH, is not significantly higher in energy than the resting state, O. Finally, to secure the involvement of the high energy EH state it is suggested that only one proton is taken up via the K-channel during catalytic turnover. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2011-01-01

The sodium-potassium (Na/K) pump is a P-type ATPase that generates Na+ and K+ concentration gradients across the cell membrane. For each 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·Pi) reveal that protonation of the high-field acidic side-chains involved in the binding sites is critical to achieve 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. PMID:21909093

Macromolecular organization of ATP synthase and complex I in whole mitochondria

PubMed Central

Davies, Karen M.; Strauss, Mike; Daum, Bertram; Kief, Jan H.; Osiewacz, Heinz D.; Rycovska, Adriana; Zickermann, Volker; Kühlbrandt, Werner

2011-01-01

We used electron cryotomography to study the molecular arrangement of large respiratory chain complexes in mitochondria from bovine heart, potato, and three types of fungi. Long rows of ATP synthase dimers were observed in intact mitochondria and cristae membrane fragments of all species that were examined. The dimer rows were found exclusively on tightly curved cristae edges. The distance between dimers along the rows varied, but within the dimer the distance between F1 heads was constant. The angle between monomers in the dimer was 70° or above. Complex I appeared as L-shaped densities in tomograms of reconstituted proteoliposomes. Similar densities were observed in flat membrane regions of mitochondrial membranes from all species except Saccharomyces cerevisiae and identified as complex I by quantum-dot labeling. The arrangement of respiratory chain proton pumps on flat cristae membranes and ATP synthase dimer rows along cristae edges was conserved in all species investigated. We propose that the supramolecular organization of respiratory chain complexes as proton sources and ATP synthase rows as proton sinks in the mitochondrial cristae ensures optimal conditions for efficient ATP synthesis. PMID:21836051

Continuous ECS-indicated recording of the proton-motive charge flux in leaves.

PubMed

Klughammer, Christof; Siebke, Katharina; Schreiber, Ulrich

2013-11-01

Technical features and examples of application of a special emitter-detector module for highly sensitive measurements of the electrochromic pigment absorbance shift (ECS) via dual-wavelength (550-520 nm) transmittance changes (P515) are described. This device, which has been introduced as an accessory of the standard, commercially available Dual-PAM-100 measuring system, not only allows steady-state assessment of the proton motive force (pmf) and its partitioning into ΔpH and ΔΨ components, but also continuous recording of the overall charge flux driven by photosynthetic light reactions. The new approach employs a double-modulation technique to derive a continuous signal from the light/dark modulation amplitude of the P515 signal. This new, continuously measured signal primarily reflects the rate of proton efflux via the ATP synthase, which under quasi-stationary conditions corresponds to the overall rate of proton influx driven by coupled electron transport. Simultaneous measurements of charge flux and CO2 uptake as a function of light intensity indicated a close to linear relationship in the light-limited range. A linear relationship between these two signals was also found for different internal CO2 concentrations, except for very low CO2, where the rate of charge flux distinctly exceeded the rate of CO2 uptake. Parallel oscillations in CO2 uptake and charge flux were induced by high CO2 and O2. The new device may contribute to the elucidation of complex regulatory mechanisms in intact leaves.

[Effects of exogenous spermidine on lipid peroxidation and membrane proton pump activity of cucumber seedling leaves under high temperature stress].

PubMed

Tian, Jing; Guo, Shi-Rong; Sun, Jin; Wang, Li-Ping; Yang, Yan-Juan; Li, Bin

2011-12-01

Taking a relatively heat-resistant cucumber (Cucumis sativus) cultivar 'Jinchun No. 4' as test material, a sand culture experiment was conducted in growth chamber to investigate the effects of foliar spraying spermidine (Spd) on the lipid peroxidation, membrane proton pump activity, and corresponding gene expression of cucumber seedling leaves under high temperature stress. Compared with the control, foliar spraying Spd increased the plant height, stem diameter, dry and fresh mass, and leaf area significantly, and inhibited the increase of leaf relative conductivity, malondialdehyde (MDA) content, and lipoxygenase (LOX) activity effectively. Foliar spraying Spd also helped to the increase of leaf plasma membrane- and tonoplast H(+)-ATPase activity, but no significant difference was observed in the gene expression levels. These results suggested that exogenous Spd could significantly decrease the leaf lipid peroxidation and increase the proton pump activity, and thus, stabilize the leaf membrane structure and function, alleviate the damage induced by high temperature stress, and enhance the heat tolerance of cucumber seedlings.

Acid suppression and surgical therapy for Barrett's oesophagus.

PubMed

de Jonge, Pieter J F; Spaander, Manon C; Bruno, Marco J; Kuipers, Ernst J

2015-02-01

Gastro-oesophageal reflux disease is a common medical problem in developed countries, and is a risk factor for the development of Barrett's oesophagus and oesophageal adenocarcinoma. Both proton pump inhibitor therapy and antireflux surgery are effective at controlling endoscopic signs and symptoms of gastro-oesophageal reflux in patients with Barrett's oesophagus, but often fail to eliminate pathological oesophageal acid exposure. The current available studies strongly suggest that acid suppressive therapy, both pharmacological as well as surgical acid suppression, can reduce the risk the development and progression in patients with Barrett's oesophagus, but are not capable of complete prevention. No significant differences have been found between pharmacological and surgical therapy. For clinical practice, patients should be prescribed a proton pump inhibitor once daily as maintenance therapy, with the dose guided by symptoms. Antireflux surgery can be a good alternative to proton pump inhibitor therapy, but should be primarily offered to patients with symptomatic reflux, and not to asymptomatic patients with the rationale to protect against cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

High-intensity polarized H- ion source for the RHIC SPIN physics

NASA Astrophysics Data System (ADS)

Zelenski, A.; Atoian, G.; Raparia, D.; Ritter, J.; Kolmogorov, A.; Davydenko, V.

2017-08-01

A novel polarization technique had been successfully implemented for the RHIC polarized H- ion source upgrade to higher intensity and polarization. In this technique a proton beam inside the high magnetic field solenoid is produced by ionization of the atomic hydrogen beam (from external source) in the He-gas ionizer cell. Further proton polarization is produced in the process of polarized electron capture from the optically-pumped Rb vapour. The use of high-brightness primary beam and large cross-sections of charge-exchange cross-sections resulted in production of high intensity H- ion beam of 85% polarization. High beam brightness and polarization resulted in 75% polarization at 23 GeV out of AGS and 60-65% beam polarization at 100-250 GeV colliding beams in RHIC. The status of un-polarized magnetron type (Cs-vapour loaded) BNL source is also discussed.

Normal and impaired charge transport in biological systems

NASA Astrophysics Data System (ADS)

Miller, John H.; Villagrán, Martha Y. Suárez; Maric, Sladjana; Briggs, James M.

2015-03-01

We examine the physics behind some of the causes (e.g., hole migration and localization that cause incorrect base pairing in DNA) and effects (due to amino acid replacements affecting mitochondrial charge transport) of disease-implicated point mutations, with emphasis on mutations affecting mitochondrial DNA (mtDNA). First we discuss hole transport and localization in DNA, including some of our quantum mechanical modeling results, as they relate to certain mutations in cancer. Next, we give an overview of electron and proton transport in the mitochondrial electron transport chain, and how such transport can become impaired by mutations implicated in neurodegenerative diseases, cancer, and other major illnesses. In particular, we report on our molecular dynamics (MD) studies of a leucine→arginine amino acid replacement in ATP synthase, encoded by the T→G point mutation at locus 8993 of mtDNA. This mutation causes Leigh syndrome, a devastating maternally inherited neuromuscular disorder, and has been found to trigger rapid tumor growth in prostate cancer cell lines. Our MD results suggest, for the first time, that this mutation adversely affects water channels that transport protons to and from the c-ring of the rotary motor ATP synthase, thus impairing the ability of the motor to produce ATP. Finally, we discuss possible future research topics for biological physics, such as mitochondrial complex I, a large proton-pumping machine whose physics remains poorly understood.

Effect of high energy electrons on H⁻ production and destruction in a high current DC negative ion source for cyclotron.

PubMed

Onai, M; Etoh, H; Aoki, Y; Shibata, T; Mattei, S; Fujita, S; Hatayama, A; Lettry, J

2016-02-01

Recently, a filament driven multi-cusp negative ion source has been developed for proton cyclotrons in medical applications. In this study, numerical modeling of the filament arc-discharge source plasma has been done with kinetic modeling of electrons in the ion source plasmas by the multi-cusp arc-discharge code and zero dimensional rate equations for hydrogen molecules and negative ions. In this paper, main focus is placed on the effects of the arc-discharge power on the electron energy distribution function and the resultant H(-) production. The modelling results reasonably explains the dependence of the H(-) extraction current on the arc-discharge power in the experiments.

Observation of the Self-Modulation Instability via Time-Resolved Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gross, M.; Engel, J.; Good, J.

Self-modulation of an electron beam in a plasma has been observed. The propagation of a long (several plasma wavelengths) electron bunch in an overdense plasma resulted in the production of multiple bunches via the self-modulation instability. Using a combination of a radio-frequency deflector and a dipole spectrometer, the time and energy structure of the self-modulated beam was measured. The longitudinal phase space measurement showed the modulation of a long electron bunch into three bunches with an approximatelymore » $$200\\text{ }\\text{ }\\mathrm{keV}/c$$ amplitude momentum modulation. Demonstrating this effect is a breakthrough for proton-driven plasma accelerator schemes aiming to utilize the same physical effect.« less

Observation of the Self-Modulation Instability via Time-Resolved Measurements

DOE PAGES

Gross, M.; Engel, J.; Good, J.; ...

2018-04-06

Self-modulation of an electron beam in a plasma has been observed. The propagation of a long (several plasma wavelengths) electron bunch in an overdense plasma resulted in the production of multiple bunches via the self-modulation instability. Using a combination of a radio-frequency deflector and a dipole spectrometer, the time and energy structure of the self-modulated beam was measured. The longitudinal phase space measurement showed the modulation of a long electron bunch into three bunches with an approximatelymore » $$200\\text{ }\\text{ }\\mathrm{keV}/c$$ amplitude momentum modulation. Demonstrating this effect is a breakthrough for proton-driven plasma accelerator schemes aiming to utilize the same physical effect.« less

Hydrogen is a preferred intermediate in the energy-conserving electron transport chain of Methanosarcina barkeri.

PubMed

Kulkarni, Gargi; Kridelbaugh, Donna M; Guss, Adam M; Metcalf, William W

2009-09-15

Methanogens use an unusual energy-conserving electron transport chain that involves reduction of a limited number of electron acceptors to methane gas. Previous biochemical studies suggested that the proton-pumping F(420)H(2) dehydrogenase (Fpo) plays a crucial role in this process during growth on methanol. However, Methanosarcina barkeri Delta fpo mutants constructed in this study display no measurable phenotype on this substrate, indicating that Fpo plays a minor role, if any. In contrast, Delta frh mutants lacking the cytoplasmic F(420)-reducing hydrogenase (Frh) are severely affected in their ability to grow and make methane from methanol, and double Delta fpo/Delta frh mutants are completely unable to use this substrate. These data suggest that the preferred electron transport chain involves production of hydrogen gas in the cytoplasm, which then diffuses out of the cell, where it is reoxidized with transfer of electrons into the energy-conserving electron transport chain. This hydrogen-cycling metabolism leads directly to production of a proton motive force that can be used by the cell for ATP synthesis. Nevertheless, M. barkeri does have the flexibility to use the Fpo-dependent electron transport chain when needed, as shown by the poor growth of the Delta frh mutant. Our data suggest that the rapid enzymatic turnover of hydrogenases may allow a competitive advantage via faster growth rates in this freshwater organism. The mutant analysis also confirms the proposed role of Frh in growth on hydrogen/carbon dioxide and suggests that either Frh or Fpo is needed for aceticlastic growth of M. barkeri.

Enhanced photocatalytic activity of graphitic carbon nitride/cadmium sulfide heterojunctions by protonating treatment

NASA Astrophysics Data System (ADS)

Yan, Mengdie; Ma, Yushuang; Zhang, Huanhuan; Ye, Boyong; Dong, Xiaoping

2018-05-01

Highly efficient visible-light-driven protonated g-C3N4 (pg-C3N4)/CdS heterojunctions with different weight ratios of CdS were prepared by treating g-C3N4 with hydrochloric acid and using an in-situ precipitation method. The structure and morphology of heterojunctions were investigated by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), UV-vis diffuse reflectance spectroscopy (DRS), Fourier transform infrared spectroscopy (FTIR) and nitrogen adsorption technology. The as-prepared pg-C3N4/CdS heterojunction with 50 wt% of g-C3N4 exhibited much higher photocatalytic activity for photodegradation of methyl orange (MO) than pg-C3N4, CdS and g-C3N4/CdS without protonation as well, which could be contributed to the activation of hydrochloric acid treatment and the improved electron-hole separation due to their overlapping band structure of CdS and pg-C3N4. A possible photocatalytic mechanism of the pg-C3N4/CdS heterojunctions with superoxide radical species as the main active species in photocatalysis was proposed on the basis of experimental results.

Proton pump inhibitors are associated with lower gastrointestinal tract bleeding in low-dose aspirin users with ischaemic heart disease.

PubMed

Miyake, Kazumasa; Akimoto, Teppei; Hanada, Yuriko; Nagoya, Hiroyuki; Kodaka, Yasuhiro; Ueki, Nobue; Kusunoki, Masafumi; Kawagoe, Tetsuro; Futagami, Seiji; Takahashi, Yasuhiro; Takano, Hitoshi; Sakamoto, Choitsu

2015-09-01

Impact of acid suppressants on lower gastrointestinal bleeding remains unclear in low-dose aspirin users; we aimed to investigate this relationship. Retrospective cohort study of low-dose aspirin users who underwent coronary angiography for ischaemic heart disease in our institution between October 2005 and December 2006; patients were evaluated for upper or lower gastrointestinal bleedings within 3 years post-angiography. 538 patients were enrolled (males, 74.4%; mean age 67.4±10.6 years). Risk for upper gastrointestinal bleeding decreased with concomitant use of statins (HR, 0.37; 95% CI, 0.15-0.89), calcium channel blockers (HR, 0.29; 95% CI, 0.10-0.85), and histamine-2 receptor antagonists (HR, 0.26; 95% CI, 0.08-0.89). Concomitant use of proton pump inhibitors tended to decrease risk of upper gastrointestinal bleeding (HR, 0.27; 95% CI, 0.06-1.18). Risk for lower gastrointestinal bleeding increased with both concomitant use of warfarin (HR, 15.68; 95% CI, 4.43-55.53) and proton pump inhibitors (HR, 6.55; 95% CI, 2.01-21.32), but not with histamine-2 receptor antagonists. Hyperuricemia lowered risk for lower gastrointestinal bleeding (HR, 0.12; 95% CI, 0.02-0.88). In low-dose aspirin users, concomitant use of proton pump inhibitors increased lower gastrointestinal bleeding risk, independent from effects on upper gastrointestinal bleeding. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Interaction physics for the stimulated Brillouin scattering of a laser in laser driven fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yadav, Pinki; Gupta, D.N.; Avinash, K., E-mail: dngupta@physics.du.ac.in

2014-07-01

Energy exchange between pump wave and ion-acoustic wave during the stimulated Brillouin Scattering process in relativistic laser-plasma interactions is studied, including the effect of damping coefficient of electron-ion collision by obeying the energy and momentum conservations. The variations of plasma density and damping coefficient of electron-ion collision change the amplitudes of the interacting wave. The relativistic mass effect modifies the dispersion relations of the interacting waves and consequently, the energy exchange during the stimulated Brillouin Scattering is affected. The collisional damping of electron-ion collision in the plasma is shown to have an important effect on the evolution of the interactingmore » waves. (author)« less

Cell-Free Synthetic Biology Chassis for Nanocatalytic Photon-to-Hydrogen Conversion

DOE PAGES

Wang, Peng; Chang, Angela Y.; Novosad, Valentyn; ...

2017-06-11

We report on entirely man-made nanobio hybrid fabricated through assembly of cell-free expressed transmembrane proton pump and semiconductor nanoparticles as an efficient nanocatalysis for photocatalytic H 2 evolution. The system produces H 2 at a turnover rate of 239 (μmole protein) -1 h -1 under green and 17742 (μmole protein) -1 h -1 under white light at ambient conditions, in water at neutral pH with methanol as a sacrificial electron donor. Robustness and flexibility of this approach allows for systemic manipulation at nanoparticle-bio interface toward directed evolution of energy transformation materials and artificial systems.

Cell-Free Synthetic Biology Chassis for Nanocatalytic Photon-to-Hydrogen Conversion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Peng; Chang, Angela Y.; Novosad, Valentyn

We report on entirely man-made nanobio hybrid fabricated through assembly of cell-free expressed transmembrane proton pump and semiconductor nanoparticles as an efficient nanocatalysis for photocatalytic H 2 evolution. The system produces H 2 at a turnover rate of 239 (μmole protein) -1 h -1 under green and 17742 (μmole protein) -1 h -1 under white light at ambient conditions, in water at neutral pH with methanol as a sacrificial electron donor. Robustness and flexibility of this approach allows for systemic manipulation at nanoparticle-bio interface toward directed evolution of energy transformation materials and artificial systems.

Dynamic control of laser driven proton beams by exploiting self-generated, ultrashort electromagnetic pulses

NASA Astrophysics Data System (ADS)

Kar, S.; Ahmed, H.; Nersisyan, G.; Brauckmann, S.; Hanton, F.; Giesecke, A. L.; Naughton, K.; Willi, O.; Lewis, C. L. S.; Borghesi, M.

2016-05-01

As part of the ultrafast charge dynamics initiated by high intensity laser irradiations of solid targets, high amplitude EM pulses propagate away from the interaction point and are transported along any stalks and wires attached to the target. The propagation of these high amplitude pulses along a thin wire connected to a laser irradiated target was diagnosed via the proton radiography technique, measuring a pulse duration of ˜20 ps and a pulse velocity close to the speed of light. The strong electric field associated with the EM pulse can be exploited for controlling dynamically the proton beams produced from a laser-driven source. Chromatic divergence control of broadband laser driven protons (upto 75% reduction in divergence of >5 MeV protons) was obtained by winding the supporting wire around the proton beam axis to create a helical coil structure. In addition to providing focussing and energy selection, the technique has the potential to post-accelerate the transiting protons by the longitudinal component of the curved electric field lines produced by the helical coil lens.

Dynamic control of laser driven proton beams by exploiting self-generated, ultrashort electromagnetic pulses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kar, S., E-mail: s.kar@qub.ac.uk; Ahmed, H.; Nersisyan, G.

As part of the ultrafast charge dynamics initiated by high intensity laser irradiations of solid targets, high amplitude EM pulses propagate away from the interaction point and are transported along any stalks and wires attached to the target. The propagation of these high amplitude pulses along a thin wire connected to a laser irradiated target was diagnosed via the proton radiography technique, measuring a pulse duration of ∼20 ps and a pulse velocity close to the speed of light. The strong electric field associated with the EM pulse can be exploited for controlling dynamically the proton beams produced from amore » laser-driven source. Chromatic divergence control of broadband laser driven protons (upto 75% reduction in divergence of >5 MeV protons) was obtained by winding the supporting wire around the proton beam axis to create a helical coil structure. In addition to providing focussing and energy selection, the technique has the potential to post-accelerate the transiting protons by the longitudinal component of the curved electric field lines produced by the helical coil lens.« less

Oblique Alfvén instabilities driven by compensated currents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malovichko, P.; Voitenko, Y.; De Keyser, J., E-mail: voitenko@oma.be

2014-01-10

Compensated-current systems created by energetic ion beams are widespread in space and astrophysical plasmas. The well-known examples are foreshock regions in the solar wind and around supernova remnants. We found a new oblique Alfvénic instability driven by compensated currents flowing along the background magnetic field. Because of the vastly different electron and ion gyroradii, oblique Alfvénic perturbations react differently on the currents carried by the hot ion beams and the return electron currents. Ultimately, this difference leads to a non-resonant aperiodic instability at perpendicular wavelengths close to the beam ion gyroradius. The instability growth rate increases with increasing beam currentmore » and temperature. In the solar wind upstream of Earth's bow shock, the instability growth time can drop below 10 proton cyclotron periods. Our results suggest that this instability can contribute to the turbulence and ion acceleration in space and astrophysical foreshocks.« less

Efficient injection of radiation-pressure-accelerated sub-relativistic protons into laser wakefield acceleration based on 10 PW lasers

NASA Astrophysics Data System (ADS)

Liu, M.; Weng, S. M.; Wang, H. C.; Chen, M.; Zhao, Q.; Sheng, Z. M.; He, M. Q.; Li, Y. T.; Zhang, J.

2018-06-01

We propose a hybrid laser-driven ion acceleration scheme using a combination target of a solid foil and a density-tailored background plasma. In the first stage, a sub-relativistic proton beam can be generated by radiation pressure acceleration in intense laser interaction with the solid foil. In the second stage, this sub-relativistic proton beam is further accelerated by the laser wakefield driven by the same laser pulse in a near-critical-density background plasma with decreasing density profile. The propagating velocity of the laser front and the phase velocity of the excited wakefield wave are effectively lowered at the beginning of the second stage. By decreasing the background plasma density gradually from near critical density along the laser propagation direction, the wake travels faster and faster, while it accelerates the protons. Consequently, the dephasing between the protons and the wake is postponed and an efficient wakefield proton acceleration is achieved. This hybrid laser-driven proton acceleration scheme can be realized by using ultrashort laser pulses at the peak power of 10 PW for the generation of multi-GeV proton beams.

The frequency of CYP2C19 genetic polymorphisms in Russian patients with peptic ulcers treated with proton pump inhibitors.

PubMed

Sychev, D A; Denisenko, N P; Sizova, Z M; Grachev, A V; Velikolug, K A

2015-01-01

Proton pump inhibitors, which are widely used as acid-inhibitory agents for the treatment of peptic ulcers, are mainly metabolized by 2C19 isoenzyme of cytochrome P450 (CYP2C19). CYP2C19 has genetic polymorphisms, associated with extensive, poor, intermediate or ultra-rapid metabolism of proton pump inhibitors. Genetic polymorphisms of CYP2C19 could be of clinical concern in the treatment of peptic ulcers with proton pump inhibitors. To investigate the frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles and genotypes in Russian patients with peptic ulcers. We retrospectively reviewed the cases of 971 patients of Caucasian origin with Russian nationality from Moscow region with endoscopically and histologically proven ulcers, 428 males (44%) and 543 females (56%). The mean age was 44.6±11.9 years (range: 15-88 years). DNA was extracted from ethylenediaminetetraacetic acid whole blood samples (10 mL). The polymorphisms CYP2C19 681G.A (CYP2C19*2, rs4244285), CYP2C19 636 G.A (CYP2C19*3, rs4986893) and CYP2C19 -806 C.T (CYP2C19*17, rs12248560) were evaluated using real-time polymerase chain reaction. Regarding CYP2C19 genotype, 317 patients (32.65%) out of 971 were CYP2C19*1/*1 carriers classified as extensive metabolizers. Three hundred and eighty-six (39.75%) with CYP2C19*1/*17 or CYP2C19*17/*17 genotype were ultra-rapid metabolizers. Two hundred and fifty-one people (25.85%) were intermediate metabolizers with CYP2C19*1/*2, CYP2C19*2/*17, CYP2C19*1/*3, CYP2C19*3/*17 genotypes. Seventeen patients (1.75%) with CYP2C19*2/*2, CYP2C19*3/*3, CYP2C19*2/*3 genotypes were poor metabolizers. The allele frequencies were the following: CYP2C19*2 - 0.140, CYP2C19*3 - 0.006, CYP2C19*17 - 0.274. There is a high frequency of CYP2C19 genotypes associated with modified response to proton pump inhibitors in Russian patients with peptic ulcers. Genotyping for CYP2C19 polymorphisms is suggested to be a useful tool for personalized dosing of proton pump inhibitors.

Resonance energy transfer improves the biological function of bacteriorhodopsin within a hybrid material built from purple membranes and semiconductor quantum dots.

PubMed

Rakovich, Aliaksandra; Sukhanova, Alyona; Bouchonville, Nicolas; Lukashev, Evgeniy; Oleinikov, Vladimir; Artemyev, Mikhail; Lesnyak, Vladimir; Gaponik, Nikolai; Molinari, Michael; Troyon, Michel; Rakovich, Yury P; Donegan, John F; Nabiev, Igor

2010-07-14

Purple membrane (PM) from bacteria Halobacterium salinarum contains a photochromic protein bacteriorhodopsin (bR) arranged in a 2D hexagonal nanocrystalline lattice (Figure 1 ). Absorption of light by the protein-bound chromophore retinal results in pumping the protons through the PM creating an electrochemical gradient which is then used by the ATPases to energize the cellular processes. Energy conversion, photochromism, and photoelectrism are the inherent effects which are employed in many bR technical applications. bR, along with the other photosensitive proteins, is not able to deal with the excess energy of photons in UV and blue spectral region and utilizes less than 0.5% of the energy from the available incident solar light for its biological function. Here, we proceed with optimization of bR functions through the engineering of a "nanoconverter" of solar energy based on semiconductor quantum dots (QDs) tagged with the PM. These nanoconverters are able to harvest light from deep-UV to the visible region and to transfer this additionally collected energy to bR via Förster resonance energy transfer (FRET). We show that specific nanobio-optical and spatial coupling of QDs (donor) and bR retinal (acceptor) provide a means to achieve FRET with efficiency approaching 100%. We have finally demonstrated that the integration of QDs within PM significantly increases the efficiency of light-driven transmembrane proton pumping, which is the main bR biological function. This new QD-PM hybrid material will have numerous optoelectronic, photonic, and photovoltaic applications based on its energy conversion, photochromism, and photoelectrism properties.

Heat driven pulse pump

NASA Technical Reports Server (NTRS)

Benner, Steve M (Inventor); Martins, Mario S. (Inventor)

2000-01-01

A heat driven pulse pump includes a chamber having an inlet port, an outlet port, two check valves, a wick, and a heater. The chamber may include a plurality of grooves inside wall of the chamber. When heated within the chamber, a liquid to be pumped vaporizes and creates pressure head that expels the liquid through the outlet port. As liquid separating means, the wick, disposed within the chamber, is to allow, when saturated with the liquid, the passage of only liquid being forced by the pressure head in the chamber, preventing the vapor from exiting from the chamber through the outlet port. A plurality of grooves along the inside surface wall of the chamber can sustain the liquid, which is amount enough to produce vapor for the pressure head in the chamber. With only two simple moving parts, two check valves, the heat driven pulse pump can effectively function over the long lifetimes without maintenance or replacement. For continuous flow of the liquid to be pumped a plurality of pumps may be connected in parallel.

Proton Transfer Dynamics at the Membrane/Water Interface: Dependence on the Fixed and Mobile pH Buffers, on the Size and Form of Membrane Particles, and on the Interfacial Potential Barrier

PubMed Central

Cherepanov, Dmitry A.; Junge, Wolfgang; Mulkidjanian, Armen Y.

2004-01-01

Crossing the membrane/water interface is an indispensable step in the transmembrane proton transfer. Elsewhere we have shown that the low dielectric permittivity of the surface water gives rise to a potential barrier for ions, so that the surface pH can deviate from that in the bulk water at steady operation of proton pumps. Here we addressed the retardation in the pulsed proton transfer across the interface as observed when light-triggered membrane proton pumps ejected or captured protons. By solving the system of diffusion equations we analyzed how the proton relaxation depends on the concentration of mobile pH buffers, on the surface buffer capacity, on the form and size of membrane particles, and on the height of the potential barrier. The fit of experimental data on proton relaxation in chromatophore vesicles from phototropic bacteria and in bacteriorhodopsin-containing membranes yielded estimates for the interfacial potential barrier for H+/OH− ions of ∼120 meV. We analyzed published data on the acceleration of proton equilibration by anionic pH buffers and found that the height of the interfacial barrier correlated with their electric charge ranging from 90 to 120 meV for the singly charged species to >360 meV for the tetra-charged pyranine. PMID:14747306

Electron transfer in biology

NASA Astrophysics Data System (ADS)

Williams, R. J. P.

Electron transfer is one of the key reactions of biology not just in catalysis of oxidation/reduction reactions but in the conversion of sources of energy such as light to usable form for chemical transformations. There are then two intriguing problems. What is the nature of the matrix in which electrons flow in a biological cell after the initial charge separation due for example to the absorption of light. Here we are examining biological structures similar to man's electronic wires and the construction must be of low resistance in what are apparently insulators - organic polymers. It has been found that the electronic conduction system is largely made from metallo-proteins associated with lipid membranes. We understand much about these biological wires today. The second problem concerns the conversion of the energy captured from the light into usable chemical form. The major synthetic step in the production of biological polymers, including proteins, DNA, RNA, polysaccharides and fats, is condensation, i.e. the removal of water in the formation of amides, esters and so on. Now these condensation reactions are driven in biology by using a drying agent in water, namely the anhydride, pyrophosphate, in a special compound ATP, adenosine triphosphate. The central problem is to discover exactly how the flow of electrons can be related to the synthesis of (bound) pyrophosphate. (In a thermodynamic sense pyrophosphate is a water soluble kinetically stable drying agent comparable with solid P2O5.) In the biological systems the connection between these different classes of reaction, electron transfer and condensation, is known to be via the production of an energized gradient of protons across the biological membrane which arises from the flow of electrons across the same membrane in the electron transport wires of biology. However we do not understand thoroughly the steps which lead from electron flow in a membrane to proton gradients in that membrane, i.e. electron/proton coupling. Again we do not understand thoroughly how subsequently the proton gradient across a membrane makes ATP, pyrophosphate. Today there is good experimental evidence as to the likely answers in principle. These analyse the coupling devices in mechanical terms. In this article I describe at first the 'wires' of biology, uncoupled simple electron flow, and then go on to the ways in which electron flow could be transduced by mechanical devices, also proteins, into proton gradients and then ATP. This will be termed coupled electron flow. The objective of the article is to stimulate participation by physical chemists in the further description of biological energy capture from light or the oxidation of hydrocarbons to a form suitable for driving chemical syntheses in a controlled manner.

Observations of a fast transverse instability in the PSR

NASA Astrophysics Data System (ADS)

Neuffer, D.; Colton, E.; Fitzgerald, D.; Hardek, T.; Hutson, R.; Macek, R.; Plum, M.; Thiessen, H.; Wang, T.-S.

1992-09-01

A fast instability with beam loss is observed in the Los Alamos Proton Storage Ring (PSR) when the injected beam current exceeds a threshold value, with both bunched and unbunched beams. Large coherent transverse oscillations occur prior to and during beam loss. The threshold depends strongly on rf voltage, beam-pulse shape, beam size, nonlinear fields, and beam environmental. Results of recent observations of the instability are reported; possible causes of the instability are discussed. Recent measurements and calculations indicate that the instability is an "e-p"-type instability, driven by coupled oscillations with electrons trapped within the proton beam. Future experiments toward further understanding of the instability are discussed, and methods of increasing PSR beam storage are suggested.

Measurement of the isolated diphoton cross section in p p collisions at s = 7 TeV with the ATLAS detector

DOE PAGES

Aad, G.; Abbott, B.; Abdallah, J.; ...

2012-01-11

Here, the ATLAS experiment has measured the production cross section of events with two isolated photons in the final state, in proton-proton collisions at √s = 7 TeV. The full data set acquired in 2010 is used, corresponding to an integrated luminosity of 37 pb –1. The background, consisting of hadronic jets and isolated electrons, is estimated with fully data-driven techniques and subtracted. The differential cross sections, as functions of the di-photon mass (m γγ), total transverse momentum (pT, γγ), and azimuthal separation (ΔΦ γγ), are presented and compared to the predictions of next-to-leading-order QCD.

TRANSITION FROM KINETIC TO MHD BEHAVIOR IN A COLLISIONLESS PLASMA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parashar, Tulasi N.; Matthaeus, William H.; Shay, Michael A.

The study of kinetic effects in heliospheric plasmas requires representation of dynamics at sub-proton scales, but in most cases the system is driven by magnetohydrodynamic (MHD) activity at larger scales. The latter requirement challenges available computational resources, which raises the question of how large such a system must be to exhibit MHD traits at large scales while kinetic behavior is accurately represented at small scales. Here we study this implied transition from kinetic to MHD-like behavior using particle-in-cell (PIC) simulations, initialized using an Orszag–Tang Vortex. The PIC code treats protons, as well as electrons, kinetically, and we address the questionmore » of interest by examining several different indicators of MHD-like behavior.« less

Radiobiological study by using laser-driven proton beams

NASA Astrophysics Data System (ADS)

Yogo, A.; Sato, K.; Nishikino, M.; Mori, M.; Teshima, T.; Numasaki, H.; Murakami, M.; Demizu, Y.; Akagi, S.; Nagayama, S.; Ogura, K.; Sagisaka, A.; Orimo, S.; Nishiuchi, M.; Pirozhkov, A. S.; Ikegami, M.; Tampo, M.; Sakaki, H.; Suzuki, M.; Daito, I.; Oishi, Y.; Sugiyama, H.; Kiriyama, H.; Okada, H.; Kanazawa, S.; Kondo, S.; Shimomura, T.; Nakai, Y.; Tanoue, M.; Sugiyama, H.; Sasao, H.; Wakai, D.; Kawachi, T.; Nishimura, H.; Bolton, P. R.; Daido, H.

2009-07-01

Particle acceleration driven by high-intensity laser systems is widely attracting interest as a potential alternative to conventional ion acceleration, including ion accelerator applications to tumor therapy. Recent works have shown that a high intensity laser pulse can produce single proton bunches of a high current and a short pulse duration. This unique feature of laser-ion acceleration can lead to progress in the development of novel ion sources. However, there has been no experimental study of the biological effects of laser-driven ion beams. We describe in this report the first demonstrated irradiation effect of laser-accelerated protons on human lung cancer cells. In-vitro A549 cells are irradiated with a proton dose of 20 Gy, resulting in a distinct formation of γ-H2AX foci as an indicator of DNA double-strand breaks. This is a pioneering result that points to future investigations of the radiobiological effects of laser-driven ion beams. The laser-driven ion beam is apotential excitation source for time-resolved determination of hydroxyl (OH) radical yield, which will explore relationship between the fundamental chemical reactions of radiation effects and consequent biological processes.

In Vitro Activities of Rabeprazole, a Novel Proton Pump Inhibitor, and Its Thioether Derivative Alone and in Combination with Other Antimicrobials against Recent Clinical Isolates of Helicobacter pylori

PubMed Central

Kawakami, Yoshiyuki; Akahane, Takayuki; Yamaguchi, Masaru; Oana, Kozue; Takahashi, Yuko; Okimura, Yukie; Okabe, Tadashi; Gotoh, Akira; Katsuyama, Tsutomu

2000-01-01

The MICs of rabeprazole sodium (RPZ), a newly developed benzimidazole proton pump inhibitor (PPI), against 133 clinical Helicobacter pylori strains revealed a higher degree of activity than the another two PPIs, lansoprazole and omeprazole. Time-kill curve assays of RPZ, when combined with amoxicillin, clarithromycin, or metronidazole, disclosed that synergistic effects were demonstrated in combination with each antibiotic examined. Moreover, no apparent antagonistic effect appeared among all of the strains tested. PMID:10639386

RHIC polarized proton-proton operation at 100 GeV in Run 15

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoefer, V.; Aschenauer, E. C.; Atoian, G.

2015-05-03

The first part of RHIC Run 15 consisted of ten weeks of polarized proton on proton collisions at a beam energy of 100 GeV at two interaction points. In this paper we discuss several of the upgrades to the collider complex that allowed for improved performance. The largest effort consisted in commissioning of the electron lenses, one in each ring, which are designed to compensate one of the two beam-beam interactions experienced by the proton bunches. The e-lenses raise the per bunch intensity at which luminosity becomes beam-beam limited. A new lattice was designed to create the phase advances necessarymore » for a beam-beam compensation with the e-lens, which also has an improved off-momentum dynamic aperture relative to previous runs. In order to take advantage of the new, higher intensity limit without suffering intensity driven emittance deterioration, other features were commissioned including a continuous transverse bunch-by-bunch damper in RHIC and a double harmonic RF cature scheme in the Booster. Other high intensity protections include improvements to the abort system and the installation of masks to intercept beam lost due to abort kicker pre-fires.« less

Dynamics of laser-driven proton beam focusing and transport into solid density matter

NASA Astrophysics Data System (ADS)

Kim, J.; McGuffey, C.; Beg, F.; Wei, M.; Mariscal, D.; Chen, S.; Fuchs, J.

2016-10-01

Isochoric heating and local energy deposition capabilities make intense proton beams appealing for studying high energy density physics and the Fast Ignition of inertial confinement fusion. To study proton beam focusing that results in high beam density, experiments have been conducted using different target geometries irradiated by a kilojoule, 10 ps pulse of the OMEGA EP laser. The beam focus was measured by imaging beam-induced Cu K-alpha emission on a Cu foil that was positioned at a fixed distance. Compared to a free target, structured targets having shapes of wedge and cone show a brighter and narrower K-alpha radiation emission spot on a Cu foil indicating higher beam focusability. Experimentally observed images with proton radiography demonstrate the existence of transverse fields on the structures. Full-scale simulations including the contribution of a long pulse duration of the laser confirm that such fields can be caused by hot electrons moving through the structures. The simulated fields are strong enough to reflect the diverging main proton beam and pinch a transverse probe beam. Detailed simulation results including the beam focusing and transport of the focused intense proton beam in Cu foil will be presented. This work was supported by the National Laser User Facility Program through Award DE-NA0002034.

Pro-oxidant mitochondrial matrix-targeted ubiquinone MitoQ10 acts as anti-oxidant at retarded electron transport or proton pumping within Complex I.

PubMed

Plecitá-Hlavatá, Lydie; Jezek, Jan; Jezek, Petr

2009-01-01

Oxidative stress of mitochondrial origin, i.e. elevated mitochondrial superoxide production, belongs to major factors determining aging and oxidative-stress-related diseases. Antioxidants, such as the mitochondria-targeted coenzyme Q, MitoQ(10), may prevent or cure these pathological conditions. To elucidate pro- and anti-oxidant action of MitoQ(10), we studied its effects on HepG2 cell respiration, mitochondrial network morphology, and rates of superoxide release (above that neutralized by superoxide dismutase) to the mitochondrial matrix (J(m)). MitoSOX Red fluorescence confocal microscopy monitoring of J(m) rates showed pro-oxidant effects of 3.5-fold increased J(m) with MitoQ(10). MitoQ(10) induced fission of the mitochondrial network which was recovered after 24h. In rotenone-inhibited HepG2 cells (i.e., already under oxidative stress) MitoQ(10) sharply decreased rotenone-induced J(m), but not together with the Complex II inhibitor thenoyltrifluoroacetone. Respiration of HepG2 cells and isolated rat liver mitochondria with MitoQ(10) increased independently of rotenone. The increase was prevented by thenoyltrifluoroacetone. These results suggest that MitoQ(10) accepts electrons prior to the rotenone-bound Q-site, and the Complex II reverse mode oxidizes MitoQ(10)H(2) to regenerate MitoQ(10). Consequently, MitoQ(10) has a pro-oxidant role in intact cells, whereas it serves as an antioxidant when Complex I-derived superoxide generation is already elevated due to electron flow retardation. Moreover, unlike mitochondrial uncoupling, MitoQ(10) exerted its antioxidant role when Complex I proton pumping was retarded by a hydrophobic amiloride, 5-(N-ethyl-N-isopropyl) amiloride. Consequently, MitoQ(10) may be useful in the treatment of diseases originating from impairment of respiratory chain Complex I due to oxidatively damaged mitochondrial DNA, when its targeted delivery to pathogenic tissues is ensured.

Polarization-controlled optimal scatter suppression in transient absorption spectroscopy

PubMed Central

Malý, Pavel; Ravensbergen, Janneke; Kennis, John T. M.; van Grondelle, Rienk; Croce, Roberta; Mančal, Tomáš; van Oort, Bart

2017-01-01

Ultrafast transient absorption spectroscopy is a powerful technique to study fast photo-induced processes, such as electron, proton and energy transfer, isomerization and molecular dynamics, in a diverse range of samples, including solid state materials and proteins. Many such experiments suffer from signal distortion by scattered excitation light, in particular close to the excitation (pump) frequency. Scattered light can be effectively suppressed by a polarizer oriented perpendicular to the excitation polarization and positioned behind the sample in the optical path of the probe beam. However, this introduces anisotropic polarization contributions into the recorded signal. We present an approach based on setting specific polarizations of the pump and probe pulses, combined with a polarizer behind the sample. Together, this controls the signal-to-scatter ratio (SSR), while maintaining isotropic signal. We present SSR for the full range of polarizations and analytically derive the optimal configuration at angles of 40.5° between probe and pump and of 66.9° between polarizer and pump polarizations. This improves SSR by (or compared to polarizer parallel to probe). The calculations are validated by transient absorption experiments on the common fluorescent dye Rhodamine B. This approach provides a simple method to considerably improve the SSR in transient absorption spectroscopy. PMID:28262765

Ultrafast Dynamics of Plasmon-Exciton Interaction of Ag Nanowire- Graphene Hybrids for Surface Catalytic Reactions

PubMed Central

Ding, Qianqian; Shi, Ying; Chen, Maodu; Li, Hui; Yang, Xianzhong; Qu, Yingqi; Liang, Wenjie; Sun, Mengtao

2016-01-01

Using the ultrafast pump-probe transient absorption spectroscopy, the femtosecond-resolved plasmon-exciton interaction of graphene-Ag nanowire hybrids is experimentally investigated, in the VIS-NIR region. The plasmonic lifetime of Ag nanowire is about 150 ± 7 femtosecond (fs). For a single layer of graphene, the fast dynamic process at 275 ± 77 fs is due to the excitation of graphene excitons, and the slow process at 1.4 ± 0.3 picosecond (ps) is due to the plasmonic hot electron interaction with phonons of graphene. For the graphene-Ag nanowire hybrids, the time scale of the plasmon-induced hot electron transferring to graphene is 534 ± 108 fs, and the metal plasmon enhanced graphene plasmon is about 3.2 ± 0.8 ps in the VIS region. The graphene-Ag nanowire hybrids can be used for plasmon-driven chemical reactions. This graphene-mediated surface-enhanced Raman scattering substrate significantly increases the probability and efficiency of surface catalytic reactions co-driven by graphene-Ag nanowire hybridization, in comparison with reactions individually driven by monolayer graphene or single Ag nanowire. This implies that the graphene-Ag nanowire hybrids can not only lead to a significant accumulation of high-density hot electrons, but also significantly increase the plasmon-to-electron conversion efficiency, due to strong plasmon-exciton coupling. PMID:27601199

Simulating Sources of Superstorm Plasmas

NASA Technical Reports Server (NTRS)

Fok, Mei-Ching

2008-01-01

We evaluated the contributions to magnetospheric pressure (ring current) of the solar wind, polar wind, auroral wind, and plasmaspheric wind, with the surprising result that the main phase pressure is dominated by plasmaspheric protons. We used global simulation fields from the LFM single fluid ideal MHD model. We embedded the Comprehensive Ring Current Model within it, driven by the LFM transpolar potential, and supplied with plasmas at its boundary including solar wind protons, polar wind protons, auroral wind O+, and plasmaspheric protons. We included auroral outflows and acceleration driven by the LFM ionospheric boundary condition, including parallel ion acceleration driven by upward currents. Our plasmasphere model runs within the CRCM and is driven by it. Ionospheric sources were treated using our Global Ion Kinetics code based on full equations of motion. This treatment neglects inertial loading and pressure exerted by the ionospheric plasmas, and will be superceded by multifluid simulations that include those effects. However, these simulations provide new insights into the respective role of ionospheric sources in storm-time magnetospheric dynamics.

Generation of quasi-monoenergetic protons from a double-species target driven by the radiation pressure of an ultraintense laser pulse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pae, Ki Hong; Kim, Chul Min, E-mail: chulmin@gist.ac.kr; Advanced Photonics Research Institute, Gwangju Institute of Science and Technology, Gwangju 61005

In laser-driven proton acceleration, generation of quasi-monoenergetic proton beams has been considered a crucial feature of the radiation pressure acceleration (RPA) scheme, but the required difficult physical conditions have hampered its experimental realization. As a method to generate quasi-monoenergetic protons under experimentally viable conditions, we investigated using double-species targets of controlled composition ratio in order to make protons bunched in the phase space in the RPA scheme. From a modified optimum condition and three-dimensional particle-in-cell simulations, we showed by varying the ion composition ratio of proton and carbon that quasi-monoenergetic protons could be generated from ultrathin plane targets irradiated withmore » a circularly polarized Gaussian laser pulse. The proposed scheme should facilitate the experimental realization of ultrashort quasi-monoenergetic proton beams for unique applications in high field science.« less

Pantoprazole: a new proton pump inhibitor.

PubMed

Jungnickel, P W

2000-11-01

This paper reviews the pharmacology, clinical efficacy, and tolerability of pantoprazole in comparison with those of other available proton pump inhibitors (PPIs). Relevant English-language research and review articles were identified by database searches of MEDLINE, International Pharmaceutical Abstracts, and UnCover, and by examining the reference lists of the articles so identified. In selecting data for inclusion, the author gave preference to full-length articles published in peer-reviewed journals. Like other PPIs, pantoprazole exerts its pharmacodynamic actions by binding to the proton pump (H+,K+ -adenosine triphosphatase) in the parietal cells, but, compared with other PPIs, its binding may be more specific for the proton pump. Pantoprazole is well absorbed when administered as an enteric-coated, delayed-release tablet, with an oral bioavailability of approximately 77%. It is hepatically metabolized via cytochrome P2C19 to hydroxypantoprazole, an inactive metabolite that subsequently undergoes sulfate conjugation. The elimination half-life ranges from 0.9 to 1.9 hours and is independent of dose. Pantoprazole has similar efficacy to other PPIs in the healing of gastric and duodenal ulcers, as well as erosive esophagitis, and as part of triple-drug regimens for the eradication of Helicobacter pylori from the gastric mucosa. It is well tolerated, with the most common adverse effects being headache, diarrhea, flatulence, and abdominal pain. In clinical studies, it has been shown to have no interactions with various other agents, including carbamazepine, cisapride, cyclosporine, digoxin, phenytoin, theophylline, and warfarin. Pantoprazole appears to be as effective as other PPIs. Its low potential for drug interactions may give it an advantage in patients taking other drugs.

Risk factors and prescription patterns of gastroesophageal reflux disease: HEAL study in Pakistan.

PubMed

Butt, Arshad Kamal; Hashemy, Irfan

2014-07-01

To determine the frequency of the use of proton-pump inhibitor therapy in patients with typical symptoms of gastroesophageal reflux disease and evaluate its risk factors. The cross-sectional study was conducted between June 2010 and February 2011 across 10 cities of Pakistan. Adult patients giving a current history of typical gastroesophageal reflux disease symptoms were included. Information on patient demography, medical history, family history, prescription patterns, lifestyle factors and dietary habits were collected. SPSS 18 was used for statistical analysis and descriptive statistics were used for the analysis of categorical and continuous variables. Of the 1010 patients enrolled, 954 (94.45%) formed the study population. Of them, 520 (54.5%) were men. The overall mean age was 41.9 +/- 12.5 years, and 439 (46%) had body mass index > or = 25 kg/m2. Further, 805 (84.4%) reported history of dyspepsia while 692 (72.5%) had gastroesophageal reflux disease during the preceding year. Family history of acid peptic disease was reported by 231 (24.2%) patients. Prior to consultation, 505 (52.9%) patients were on proton-pump inhibitors. Following consultation, 923 (96.8%) patients were prescribed proton-pump inhibitors, with omeprazole being the preferred choice in 577 (60.5%). Associated risk factors included regular use of nonsteroidal anti-inflammatory drugs in 355 (37.2%) and current smoking in 210 (22.0%). Consuming spicy meals was reported by 666 (70.0%). Nearly half the patients with typical gastroesophageal reflux disease symptoms were overweight, and a majority consumed spicy meals. Proton-pump inhibitors were widely prescribed, and omeprazole was the preferred choice of drug.

Prescribing patterns and economic costs of proton pump inhibitors in Colombia

PubMed Central

Fernández, Alejandra; Castrillón, Juan Daniel; Campo, Carlos Felipe; Echeverri, Luis Felipe; Gaviria, Andrés; Londoño, Manuel José; Ochoa, Sergio Andrés; Ruíz, Joaquín Octavio

2013-01-01

Objective: To determine the prescribing patterns for proton pump inhibitors and to estimate the economic cost of their use in a group of patients affiliated with the Colombian Health System. Methods: This is a descriptive observational study. Data for analysis consisted of prescriptions dispensed between October 1st, 2010 and October 31st, 2010 and were collected from a systematic database of 4.2 million members. Socio-demographic variables were considered along with the defined daily dose,comedication, convenience of the indication for proton pump inhibitor use and costs. Results: In this study, 113,560 prescriptions were dispensed in 89 cities, mostly to women (57.6%) with a mean age of 54.4 ± 18.7 years; the drugs were omeprazole (n= 111.294; 97.81%),esomeprazole (n= 1.378; 1.2%), lansoprazole (n= 524; 0.4%), pantoprazole and rabeprazole. The indication for 87.349 of the formulas (76.9%) was justified and statistically associated with the use of NSAIDs, antithrombotics, corticosteroids, anti-ulcer, antibiotics and prokinetics. No justification was found for 26.211 (23.1%) of the prescriptions, which were associated with antidiabetics, antihypertensives, hypolipidemics and others (p <0.001).The annual justified cost was estimated to be US$ 1,654,701 and the unjustified cost was estimated to be U.S. $2,202,590, as calculated using the minimum reference prices. Discussion: Each month, the Colombian health system is overloaded by unjustified costs that include payments for non-approved indications of proton pump inhibitors and for drugs outside the list of essential medications. This issue is contributing to rising costs of healthcare in Colombia. PMID:24892316

Water exit pathways and proton pumping mechanism in B-type cytochrome c oxidase from molecular dynamics simulations.

PubMed

Yang, Longhua; Skjevik, Åge A; Han Du, Wen-Ge; Noodleman, Louis; Walker, Ross C; Götz, Andreas W

2016-09-01

Cytochrome c oxidase (CcO) is a vital enzyme that catalyzes the reduction of molecular oxygen to water and pumps protons across mitochondrial and bacterial membranes. While proton uptake channels as well as water exit channels have been identified for A-type CcOs, the means by which water and protons exit B-type CcOs remain unclear. In this work, we investigate potential mechanisms for proton transport above the dinuclear center (DNC) in ba3-type CcO of Thermus thermophilus. Using long-time scale, all-atom molecular dynamics (MD) simulations for several relevant protonation states, we identify a potential mechanism for proton transport that involves propionate A of the active site heme a3 and residues Asp372, His376 and Glu126(II), with residue His376 acting as the proton-loading site. The proposed proton transport process involves a rotation of residue His376 and is in line with experimental findings. We also demonstrate how the strength of the salt bridge between residues Arg225 and Asp287 depends on the protonation state and that this salt bridge is unlikely to act as a simple electrostatic gate that prevents proton backflow. We identify two water exit pathways that connect the water pool above the DNC to the outer P-side of the membrane, which can potentially also act as proton exit transport pathways. Importantly, these water exit pathways can be blocked by narrowing the entrance channel between residues Gln151(II) and Arg449/Arg450 or by obstructing the entrance through a conformational change of residue Tyr136, respectively, both of which seem to be affected by protonation of residue His376. Copyright © 2016 Elsevier B.V. All rights reserved.

Fluid driven reciprocating apparatus

DOEpatents

Whitehead, J.C.

1997-04-01

An apparatus is described comprising a pair of fluid driven pump assemblies in a back-to-back configuration to yield a bi-directional pump. Each of the pump assemblies includes a piston or diaphragm which divides a chamber therein to define a power section and a pumping section. An intake-exhaust valve is connected to each of the power sections of the pump chambers, and function to direct fluid, such as compressed air, into the power section and exhaust fluid therefrom. At least one of the pistons or diaphragms is connected by a rod assembly which is constructed to define a signal valve, whereby the intake-exhaust valve of one pump assembly is controlled by the position or location of the piston or diaphragm in the other pump assembly through the operation of the rod assembly signal valve. Each of the pumping sections of the pump assemblies are provided with intake and exhaust valves to enable filling of the pumping section with fluid and discharging fluid therefrom when a desired pressure has been reached. 13 figs.

Fluid driven recipricating apparatus

DOEpatents

Whitehead, John C.

1997-01-01

An apparatus comprising a pair of fluid driven pump assemblies in a back-to-back configuration to yield a bi-directional pump. Each of the pump assemblies includes a piston or diaphragm which divides a chamber therein to define a power section and a pumping section. An intake-exhaust valve is connected to each of the power sections of the pump chambers, and function to direct fluid, such as compressed air, into the power section and exhaust fluid therefrom. At least one of the pistons or diaphragms is connected by a rod assembly which is constructed to define a signal valve, whereby the intake-exhaust valve of one pump assembly is controlled by the position or location of the piston or diaphragm in the other pump assembly through the operation of the rod assembly signal valve. Each of the pumping sections of the pump assemblies are provided with intake and exhaust valves to enable filling of the pumping section with fluid and discharging fluid therefrom when a desired pressure has been reached.

Controlling laser driven protons acceleration using a deformable mirror at a high repetition rate

NASA Astrophysics Data System (ADS)

Noaman-ul-Haq, M.; Sokollik, T.; Ahmed, H.; Braenzel, J.; Ehrentraut, L.; Mirzaie, M.; Yu, L.-L.; Sheng, Z. M.; Chen, L. M.; Schnürer, M.; Zhang, J.

2018-03-01

We present results from a proof-of-principle experiment to optimize laser driven protons acceleration by directly feeding back its spectral information to a deformable mirror (DM) controlled by evolutionary algorithms (EAs). By irradiating a stable high-repetition rate tape driven target with ultra-intense pulses of intensities ∼1020 W/ cm2, we optimize the maximum energy of the accelerated protons with a stability of less than ∼5% fluctuations near optimum value. Moreover, due to spatio-temporal development of the sheath field, modulations in the spectrum are also observed. Particularly, a prominent narrow peak is observed with a spread of ∼15% (FWHM) at low energy part of the spectrum. These results are helpful to develop high repetition rate optimization techniques required for laser-driven ion accelerators.

Measuring H(+) Pumping and Membrane Potential Formation in Sealed Membrane Vesicle Systems.

PubMed

Wielandt, Alex Green; Palmgren, Michael G; Fuglsang, Anja Thoe; Günther-Pomorski, Thomas; Justesen, Bo Højen

2016-01-01

The activity of enzymes involved in active transport of matter across lipid bilayers can conveniently be assayed by measuring their consumption of energy, such as ATP hydrolysis, while it is more challenging to directly measure their transport activities as the transported substrate is not converted into a product and only moves a few nanometers in space. Here, we describe two methods for the measurement of active proton pumping across lipid bilayers and the concomitant formation of a membrane potential, applying the dyes 9-amino-6-chloro-2-methoxyacridine (ACMA) and oxonol VI. The methods are exemplified by assaying transport of the Arabidopsis thaliana plasma membrane H(+)-ATPase (proton pump), which after heterologous expression in Saccharomyces cerevisiae and subsequent purification has been reconstituted in proteoliposomes.

NSAID gastropathy and enteropathy: distinct pathogenesis likely necessitates distinct prevention strategies

PubMed Central

Wallace, John L

2012-01-01

The mechanisms underlying the ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to cause ulceration in the stomach and proximal duodenum are well understood, and this injury can largely be prevented through suppression of gastric acid secretion (mainly with proton pump inhibitors). In contrast, the pathogenesis of small intestinal injury induced by NSAIDs is less well understood, involving more complex mechanisms than those in the stomach and proximal duodenum. There is clear evidence for important contributions to NSAID enteropathy of enteric bacteria, bile and enterohepatic recirculation of the NSAID. There is no evidence that suppression of gastric acid secretion will reduce the incidence or severity of NSAID enteropathy. Indeed, clinical data suggest little, if any, benefit. Animal studies suggest a significant exacerbation of NSAID enteropathy when proton pump inhibitors are co-administered with the NSAID. This worsening of damage appears to be linked to changes in the number and types of bacteria in the small intestine during proton pump inhibitor therapy. The distinct mechanisms of NSAID-induced injury in the stomach/proximal duodenum versus the more distal small intestine likely dictate distinct strategies for prevention. PMID:21627632

A rapid Fourier transform infrared spectroscopic method for analysis of certain proton pump inhibitors in binary and ternary mixtures

NASA Astrophysics Data System (ADS)

Khashaba, Pakinaz Y.; Ali, Hassan Refat H.; El-Wekil, Mohamed M.

2018-02-01

A simple and non-destructive FTIR method was used to determine certain proton pump inhibitors (PPIs) in binary and ternary mixtures. Proton pump inhibitors (PPIs); omeprazole (OMZ), esomeprazole (EZM), lansoprazole (LAN), pantoprazole sodium (PAN sodium) and rabeprazole sodium (RAB sodium) in binary mixture with domperidone (DOM) and ternary mixture of OMZ, clarithromycin (CLM) and tinidazole (TNZ) were determined in the solid-state by FTIR spectroscopy for the first time. The method was validated according to ICH-guidelines where linearity was ranged from 20 to 850 μg/g and 20-360 μg/g for PPIs and DOM, respectively in binary mixtures and 10-400, 100-8000 and 150-14,000 μg/g for OMZ, CLM and TNZ, respectively. Limits of detection were found to be 6-100 and 9-100 μg/g for PPIs and DOM, respectively and 4, 40 and 50 μg/g for OMZ, CLM and TNZ, respectively. The method was applied successfully for determination of the cited drugs in their respective pharmaceutical dosage forms.

Adapting High Brightness Relativistic Electron Beams for Ultrafast Science

NASA Astrophysics Data System (ADS)

Scoby, Cheyne Matthew

This thesis explores the use of ultrashort bunches generated by a radiofrequency electron photoinjector driven by a femtosecond laser. Rf photoinjector technology has been developed to generate ultra high brightness beams for advanced accelerators and to drive advanced light source applications. The extremely good quality of the beams generated by this source has played a key role in the development of 4th generation light sources such as the Linac Coherent Light Source, thus opening the way to studies of materials science and biological systems with high temporal and spatial resolution. At the Pegasus Photoinjector Lab, we have developed the application of a BNL/SLAC/UCLA 1.6-cell rf photoinjector as a tool for ultrafast science in its own right. It is the aim of this work to explore the generation of ultrashort electron bunches, give descriptions of the novel ultrafast diagnostics developed to be able to characterize the electron bunch and synchronize it with a pump laser, and share some of the scientific results that were obtained with this technology at the UCLA Pegasus laboratory. This dissertation explains the requirements of the drive laser source and describes the principles of rf photoinjector design and operation necessary to produce electron bunches with an rms longitudinal length < 100 femtoseconds containing 107 - 108 electrons per bunch. In this condition, when the laser intensity is sufficiently high, multiphoton photoemission is demonstrated to be more efficient in terms of charge yield than single photon photoemission. When a short laser pulse hits the cathode the resulting beam dynamics are dominated by a strong space charge driven longitudinal expansion which leads to the creation of a nearly ideal uniformly filled ellipsoidal distribution. These beam distributions are characterized by linear space charge forces and hence by high peak brightness and small transverse emittances. This regime of operation of the RF photoinjector is also termed the “blow-out regime.” When the beam charge is maintained low, ultrashort electron bunches can be obtained enabling novel applications such as single shot Femtosecond Relativistic Electron Diffraction (FRED). High precision temporal diagnostic and synchronization techniques are integral to the use of femtosecond electron bunches for ultrafast science. An x-band rf streak camera provides measurements of the longitudinal profiles of sub-ps electron bunches. Spatial encoded electro-optic timestamping is developed to overcome the inherent rf-laser synchronization errors in rf photoinjectors. The ultrafast electron beams generated with the RF photoenjector are employed in pump-probe experiments wherein a target is illuminated with an intense pump laser to induce a transient behavior in the sample. FRED is used to study the melting of gold after heating with an intense femtosecond laser pulse. In a first experiment we study the process by taking different single-shot diffraction patterns at varying delays between the pump an probe beams. In a second experiment a variation of the technique is employed using the rf streak camera to time-stretch the beam after it has diffraction from the sample in order to capture the full melting dynamics in a single shot. Finally, relativistic ultrashort electron bunches are used as a probe of plasma dynamics in electron radiography/shadowgraphy experiments. This technique is used to study photoemission with intense laser pulses and the evolution of electromagnetic fields in a photoinduced dense plasma. This experiment is also performed in two different modes: one where different pictures are acquired at different time delays, and the other where a single streak image is used to obtain visualization of the propagation electromagnetic fields with an unprecedented 35 femtosecond resolution.

Anomalous electron spin decoherence in an optically pumped quantum dot

NASA Astrophysics Data System (ADS)

Shi, Xiaofeng; Sham, L. J.

2013-03-01

We study the nuclear-spin-fluctuation induced spin decoherence of an electron (SDE) in an optically pumped quantum dot. The SDE is computed in terms of the steady distribution of the nuclear field (SDNF) formed through the hyperfine interaction (HI) with two different nuclear species in the dot. A feedback loop between the optically driven electron spin and the nuclear spin ensemble determines the SDNF [W. Yang and L. J. Sham, Phy. Rev. B 85, 235319(2012)]. Different from that work and others reviewed therein, where a bilinear HI, SαIβ , between the electron (or hole) spin S and the nuclear spin I is used, we use an effective nonlinear interaction of the form SαIβIγ derived from the Fermi-contact HI. Our feedback loop forms a multi-peak SDNF in which the SDE shows remarkable collapses and revivals in nanosecond time scale. Such an anomalous SDE results from a quantum interference effect of the electron Larmor precession in a multi-peak effective magnetic field. In the presence of a bilinear HI that suppresses the nuclear spin fluctuation, the non-Markovian SDE persists whenever there are finite Fermi contact interactions between two or more kinds of nuclei and the electron in the quantum dot. This work is supported by NSF(PHY 1104446) and the US Army Research Office MURI award W911NF0910406.

Light-driven, proton-controlled, catalytic aerobic C-H oxidation mediated by a Mn(III) porphyrinoid complex.

PubMed

Neu, Heather M; Jung, Jieun; Baglia, Regina A; Siegler, Maxime A; Ohkubo, Kei; Fukuzumi, Shunichi; Goldberg, David P

2015-04-15

The visible light-driven, catalytic aerobic oxidation of benzylic C-H bonds was mediated by a Mn(III) corrolazine complex. To achieve catalytic turnovers, a strict selective requirement for the addition of protons was established. The resting state of the catalyst was unambiguously characterized by X-ray diffraction as [Mn(III)(H2O)(TBP8Cz(H))](+), in which a single, remote site on the ligand is protonated. If two remote sites are protonated, however, reactivity with O2 is shut down. Spectroscopic methods revealed that the related Mn(V)(O) complex is also protonated at the same remote site at -60 °C, but undergoes valence tautomerization upon warming.

Pilot Field Demonstration of Alternative Fuels in Force Projection Petroleum and Water Distribution Equipment

DTIC Science & Technology

2014-09-04

They included two Force Projection Technology (FPT) diesel driven pumping assemblies of 350 and 600 gallons per minute (GPM), and the Advanced...Army Tank Automotive Research Development and Engineering Center (TARDEC). They included two Force Projection Technology (FPT) diesel driven...research programs. The first two systems identified were Force Projection Technology (FPT) diesel -driven pumping assemblies of 350 and 600 gallons per

Efficacy of Proton Pump Inhibitors for Patients with Duodenal Ulcers: A Pairwise and Network Meta-Analysis of Randomized Controlled Trials

PubMed Central

Hu, Zhan-Hong; Shi, Ai-Ming; Hu, Duan-Min; Bao, Jun-Jie

2017-01-01

Background/Aim: To compare the efficacy and tolerance of different proton pump inhibitors (PPIs) in different doses for patients with duodenal ulcers. Materials and Methods: An electronic database was searched to collect all randomized clinical trials (RCTs), and a pairwise and network meta-analysis were performed. Results: A total of 24 RCTs involving 6188 patients were included. The network meta-analysis showed that there were no significant differences for the 4-week healing rate of duodenal ulcer treated with different PPI regimens except pantoprazle 40 mg/d versus lansoprazole 15 mg/d [Relative risk (RR) = 3.57; 95% confidence interval (CI) = 1.36–10.31)] and lansoprazole 30 mg/d versus lansoprazole 15 mg/d (RR = 2.45; 95% CI = 1.01–6.14). In comparison with H2 receptor antagonists (H2 RA), pantoprazole 40 mg/d and lansoprazole 30 mg/d significantly increase the healing rate (RR = 2.96; 95% CI = 1.78–5.14 and RR = 2.04; 95% CI = 1.13–3.53, respectively). There was no significant difference for the rate of adverse events between different regimens, including H2 RA for a duration of 4-week of follow up. Conclusion: There was no significant difference for the efficacy and tolerance between the ordinary doses of different PPIs with the exception of lansoprazle 15 mg/d. PMID:28139495

Effects of Helicobacter pylori infection and long-term proton pump inhibitor use on enterochromaffin-like cells

PubMed Central

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

Proton Pump Inhibitor Use Is Associated With a Reduced Risk of Infection with Intestinal Protozoa.

PubMed

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 < .0001). Patients taking a PPI were statistically less likely to have an intestinal 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.

Coherent evolution of parahydrogen induced polarisation using laser pump, NMR probe spectroscopy: Theoretical framework and experimental observation.

PubMed

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.

46 CFR 131.340 - Recommended placard for emergency instructions.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Keep bilges dry to prevent loss of stability from water in bilges. Use power-driven bilge pump, hand pump, and buckets to dewater. (3) Align fire pumps to serve as bilge pumps if possible. (4) Check, for...

46 CFR 131.340 - Recommended placard for emergency instructions.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Keep bilges dry to prevent loss of stability from water in bilges. Use power-driven bilge pump, hand pump, and buckets to dewater. (3) Align fire pumps to serve as bilge pumps if possible. (4) Check, for...

46 CFR 131.340 - Recommended placard for emergency instructions.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Keep bilges dry to prevent loss of stability from water in bilges. Use power-driven bilge pump, hand pump, and buckets to dewater. (3) Align fire pumps to serve as bilge pumps if possible. (4) Check, for...

46 CFR 122.512 - Recommended emergency instructions format.

Code of Federal Regulations, 2014 CFR

2014-10-01

... in the vessel. (ii) Keep bilges dry to prevent loss of stability due to water in bilges. Use power driven bilge pump, hand pump, and buckets to dewater. (iii) Align fire pumps to use as bilge pump if...

46 CFR 122.512 - Recommended emergency instructions format.

Code of Federal Regulations, 2013 CFR

2013-10-01

... in the vessel. (ii) Keep bilges dry to prevent loss of stability due to water in bilges. Use power driven bilge pump, hand pump, and buckets to dewater. (iii) Align fire pumps to use as bilge pump if...

46 CFR 122.512 - Recommended emergency instructions format.

Code of Federal Regulations, 2012 CFR

2012-10-01

... in the vessel. (ii) Keep bilges dry to prevent loss of stability due to water in bilges. Use power driven bilge pump, hand pump, and buckets to dewater. (iii) Align fire pumps to use as bilge pump if...

Electron-proton spectrometer design summary

NASA Technical Reports Server (NTRS)

1972-01-01

The electron-proton spectrometer (EPS) will be placed aboard the Skylab in order to provide data from which electron and proton radiation dose can be determined. The EPS has five sensors, each consisting of a shielded silicon detector. These provide four integral electron channels and five integral proton channels from which can be deduced four differential proton increments.

Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser.

PubMed

Nogly, Przemyslaw; Weinert, Tobias; James, Daniel; Carbajo, Sergio; Ozerov, Dmitry; Furrer, Antonia; Gashi, Dardan; Borin, Veniamin; Skopintsev, Petr; Jaeger, Kathrin; Nass, Karol; Båth, Petra; Bosman, Robert; Koglin, Jason; Seaberg, Matthew; Lane, Thomas; Kekilli, Demet; Brünle, Steffen; Tanaka, Tomoyuki; Wu, Wenting; Milne, Christopher; White, Thomas; Barty, Anton; Weierstall, Uwe; Panneels, Valerie; Nango, Eriko; Iwata, So; Hunter, Mark; Schapiro, Igor; Schertler, Gebhard; Neutze, Richard; Standfuss, Jörg

2018-06-14

Ultrafast isomerization of retinal is the primary step in photoresponsive biological functions including vision in humans and ion-transport across bacterial membranes. We studied the sub-picosecond structural dynamics of retinal isomerization in the light-driven proton pump bacteriorhodopsin using an x-ray laser. A series of structural snapshots with near-atomic spatial and temporal resolution in the femtosecond regime show how the excited all- trans retinal samples conformational states within the protein binding pocket prior to passing through a twisted geometry and emerging in the 13 -cis conformation. Our findings suggest ultrafast collective motions of aspartic acid residues and functional water molecules in the proximity of the retinal Schiff base as a key ingredient for this stereo-selective and efficient photochemical reaction. Copyright © 2018, American Association for the Advancement of Science.

Occupational Airborne Contact Dermatitis From Proton Pump Inhibitors.

PubMed

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.

Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits

PubMed Central

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

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. PMID:29491719

Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits.

PubMed

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.

[Development of a perforated peptic ulcer in a child during high dose prednisolone treatment].

PubMed

Moll Harboe, Kirstine; Midtgaard, Helle; Wewer, Vibeke; Cortes, Dina

2012-09-24

Since perforated peptic ulcer is uncommon in children proton pump inhibitor prophylaxis is not routinely recommended when children are treated with high dose steroids. We describe a case of perforated ulcer in a six-year-old patient with nephrotic syndrome treated with high dose prednisolone. Initially, ulcer was not suspected due to uncharacteristic symptoms. The child developed peritoneal signs and surgery revealed a perforated peptic ulcer in the stomach. We recommend treatment with proton pump inhibitors if children, who are treated with high dose steroids develop abdominal symptoms, which can be caused by an ulcus.

Ultrafast proton shuttling in Psammocora cyan fluorescent protein.

PubMed

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 involving a short hydrogen bond. At any time in the reaction, the proton is localized on either the chromophore or Glu-167, which implies that most likely no low-barrier hydrogen bond exists between these molecular groups. This work supports the notion that proton transfer in biological systems, be it in an electronic excited or ground state, can be an intrinsically fast process that occurs on a 100 fs time scale. PsamFP488 represents an attractive model system that poses an ultrafast proton transfer regime in discrete steps. It constitutes a valuable model system in addition to wild type GFP, where proton transfer is relatively slow, and the S65T/H148D GFP mutant, where the effects of low-barrier hydrogen bonds dominate.

Value of pH regulators in the diagnosis, prognosis and treatment of cancer.

PubMed

Granja, Sara; Tavares-Valente, Diana; Queirós, Odília; Baltazar, Fátima

2017-04-01

Altered metabolism, associated with acidification of the extracellular milieu, is one of the major features of cancer. As pH regulation is crucial for the maintenance of all biological functions, cancer cells rely on the activity of lactate exporters and proton transporters to regulate their intracellular pH. The major players in cancer pH regulation are proton pump ATPases, sodium-proton exchangers (NHEs), monocarboxylate transporters (MCTs), carbonic anhydrases (CAs) and anion exchangers (AEs), which have been shown to be upregulated in several human malignancies. Thanks to the activity of the proton pumps and transporters, tumours acidify their microenvironment, becoming more aggressive and resistant to therapy. Thus, targeting tumour pH may contribute to more effective anticancer strategies for controlling tumour progression and therapeutic resistance. In the present study, we review the role of the main pH regulators expressed in human cancer cells, including their diagnostic and prognostic value, as well as their usefulness as therapeutic targets. Copyright © 2017 Elsevier Ltd. All rights reserved.

46 CFR 28.840 - Means for stopping pumps, ventilation, and machinery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... pumps, ventilation, and machinery. All electrically driven fuel oil transfer pumps, fuel oil unit and service pumps, and ventilation fans shall be fitted with remote controls from a readily accessible... 46 Shipping 1 2014-10-01 2014-10-01 false Means for stopping pumps, ventilation, and machinery. 28...

46 CFR 28.840 - Means for stopping pumps, ventilation, and machinery.

Code of Federal Regulations, 2010 CFR

2010-10-01

... pumps, ventilation, and machinery. All electrically driven fuel oil transfer pumps, fuel oil unit and service pumps, and ventilation fans shall be fitted with remote controls from a readily accessible... 46 Shipping 1 2010-10-01 2010-10-01 false Means for stopping pumps, ventilation, and machinery. 28...

46 CFR 28.840 - Means for stopping pumps, ventilation, and machinery.

Code of Federal Regulations, 2013 CFR

2013-10-01

... pumps, ventilation, and machinery. All electrically driven fuel oil transfer pumps, fuel oil unit and service pumps, and ventilation fans shall be fitted with remote controls from a readily accessible... 46 Shipping 1 2013-10-01 2013-10-01 false Means for stopping pumps, ventilation, and machinery. 28...

46 CFR 28.840 - Means for stopping pumps, ventilation, and machinery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... pumps, ventilation, and machinery. All electrically driven fuel oil transfer pumps, fuel oil unit and service pumps, and ventilation fans shall be fitted with remote controls from a readily accessible... 46 Shipping 1 2012-10-01 2012-10-01 false Means for stopping pumps, ventilation, and machinery. 28...

46 CFR 28.840 - Means for stopping pumps, ventilation, and machinery.

Code of Federal Regulations, 2011 CFR

2011-10-01

... pumps, ventilation, and machinery. All electrically driven fuel oil transfer pumps, fuel oil unit and service pumps, and ventilation fans shall be fitted with remote controls from a readily accessible... 46 Shipping 1 2011-10-01 2011-10-01 false Means for stopping pumps, ventilation, and machinery. 28...

First Evidence of Vibrationally Driven Bimolecular Reactions in Solution: Reactions of Br Atoms with Dimethylsulfoxide and Methanol.

PubMed

Shin, Jae Yoon; Shaloski, Michael A; Crim, F Fleming; Case, Amanda S

2017-03-23

We present evidence for vibrational enhancement of the rate of bimolecular reactions of Br atoms with dimethylsulfoxide (DMSO) and methanol (CH 3 OH) in the condensed phase. The abstraction of a hydrogen atom from either of these solvents by a Br atom is highly endoergic: 3269 cm -1 for DMSO and 1416 or 4414 cm -1 for CH 3 OH, depending on the hydrogen atom abstracted. Thus, there is no thermal abstraction reaction at room temperature. Broadband electronic transient absorption shows that following photolysis of bromine precursors Br atoms form van der Waals complexes with the solvent molecules in about 5 ps and this Br • -solvent complex undergoes recombination. To explore the influence of vibrational energy on the abstraction reactions, we introduce a near-infrared (NIR) pump pulse following the photolysis pulse to excite the first overtone of the C-H (or O-H) stretch of the solvent molecules. Using single-wavelength detection, we observe a loss of the Br • -solvent complex that requires the presence of both photolysis and NIR pump pulses. Moreover, the magnitude of this loss depends on the NIR wavelength. Although this loss of reactive Br supports the notion of vibrationally driven chemistry, it is not concrete evidence of the hydrogen-abstraction reaction. To verify that the loss of reactive Br results from the vibrationally driven bimolecular reaction, we examine the pH dependence of the solution (as a measure of the formation of the HBr product) following long-time irradiation of the sample with both photolysis and NIR pump beams. We observe that when the NIR beam is on-resonance, the hydronium ion concentration increases fourfold as compared to that when it is off-resonance, suggesting the formation of HBr via a vibrationally driven hydrogen-abstraction reaction in solution.

Enhanced proton acceleration from an ultrathin target irradiated by laser pulses with plateau ASE.

PubMed

Wang, Dahui; Shou, Yinren; Wang, Pengjie; Liu, Jianbo; Li, Chengcai; Gong, Zheng; Hu, Ronghao; Ma, Wenjun; Yan, Xueqing

2018-02-07

We report a simulation study on proton acceleration driven by ultraintense laser pulses with normal contrast (10 7 -10 9 ) containing nanosecond plateau amplified spontaneous emission (ASE). It's found in hydrodynamic simulations that if the thickness of the targets lies in the range of hundreds nanometer matching the intensity and duration of ASE, the ablation pressure would push the whole target in the forward direction with speed exceeding the expansion velocity of plasma, resulting in a plasma density profile with a long extension at the target front and a sharp gradient at the target rear. When the main pulse irradiates the plasma, self-focusing happens at the target front, producing highly energetic electrons through direct laser acceleration(DLA) building the sheath field. The sharp plasma gradient at target rear ensures a strong sheath field. 2D particle-in-cell(PIC) simulations reveal that the proton energy can be enhanced by a factor of 2 compared to the case of using micrometer-thick targets.

Structure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM

PubMed Central

Zhou, Anna; Rohou, Alexis; Schep, Daniel G; Bason, John V; Montgomery, Martin G; Walker, John E; Grigorieff, Nikolaus; Rubinstein, John L

2015-01-01

Adenosine triphosphate (ATP), the chemical energy currency of biology, is synthesized in eukaryotic cells primarily by the mitochondrial ATP synthase. ATP synthases operate by a rotary catalytic mechanism where proton translocation through the membrane-inserted FO region is coupled to ATP synthesis in the catalytic F1 region via rotation of a central rotor subcomplex. We report here single particle electron cryomicroscopy (cryo-EM) analysis of the bovine mitochondrial ATP synthase. Combining cryo-EM data with bioinformatic analysis allowed us to determine the fold of the a subunit, suggesting a proton translocation path through the FO region that involves both the a and b subunits. 3D classification of images revealed seven distinct states of the enzyme that show different modes of bending and twisting in the intact ATP synthase. Rotational fluctuations of the c8-ring within the FO region support a Brownian ratchet mechanism for proton-translocation-driven rotation in ATP synthases. DOI: http://dx.doi.org/10.7554/eLife.10180.001 PMID:26439008

Fuel system for rotary distributor fuel injection pump

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klopfer, K.H.; Kelly, W.W.

1993-06-01

In a fuel injection pump having a drive shaft, a pump rotor driven by the drive shaft, reciprocating pumping means with periodic intake and pumping strokes to periodically receive an intake charge of fuel and deliver fuel at high pressure for fuel injection is described; a distributor head with a plurality of angularly spaced distributor outlets, the pump rotor providing a distributor rotor with a distributor port connected to the pumping means, the distributor rotor being rotatably mounted in the distributor head for sequential registration of the distributor port with the distributor outlets for distributing said high pressure delivery ofmore » fuel thereto; a fuel system for supplying fuel to the pumping means, having an end chamber at one end of the pump rotor and a fuel supply pump driven by the drive shaft and having an inlet and outlet, the supply pump outlet being connected to the end chamber for supplying fuel thereto, and a pressure regulator for regulating the fuel pressure in the end chamber; and a control valve connected between the pumping means and the end chamber and selectively opened during the intake strokes to supply fuel to the pumping means from the end chamber and during the pumping strokes to spill fuel from the pumping means into the end chamber to terminate said high pressure delivery of fuel; the improvement wherein the fuel system comprises a fuel return passage connected in series with the end chamber downstream thereof, wherein the pressure regulator is mounted in the return passage for regulating the upstream fuel pressure, including the upstream fuel pressure within the end chamber, and is connected for conducting excess fuel for return to the supply pump inlet, and wherein the supply pump is driven by the drive shaft to supply fuel at a rate exceeding the rate of said high pressure delivery of fuel for fuel injection and to provide excess fuel flow continuously through the end chamber and return passage to the pressure regulator.« less

Harvesting multiple electron-hole pairs generated through plasmonic excitation of Au nanoparticles.

PubMed

Kim, Youngsoo; Smith, Jeremy G; Jain, Prashant K

2018-05-07

Multi-electron redox reactions, although central to artificial photosynthesis, are kinetically sluggish. Amidst the search for synthetic catalysts for such processes, plasmonic nanoparticles have been found to catalyse multi-electron reduction of CO 2 under visible light. This example motivates the need for a general, insight-driven framework for plasmonic catalysis of such multi-electron chemistry. Here, we elucidate the principles underlying the extraction of multiple redox equivalents from a plasmonic photocatalyst. We measure the kinetics of electron harvesting from a gold nanoparticle photocatalyst as a function of photon flux. Our measurements, supported by theoretical modelling, reveal a regime where two-electron transfer from the excited gold nanoparticle becomes prevalent. Multiple electron harvesting becomes possible under continuous-wave, visible-light excitation of moderate intensity due to strong interband transitions in gold and electron-hole separation accomplished using a hole scavenger. These insights will help expand the utility of plasmonic photocatalysis beyond CO 2 reduction to other challenging multi-electron, multi-proton transformations such as N 2 fixation.

TMDs and GPDs at a future Electron-Ion Collider

DOE PAGES

Ent, Rolf

2016-06-21

With two options studied at Brookhaven National Lab and Jefferson Laboratory the U.S., an Electron-Ion Collider (EIC) of energy √s=20-100 GeV was under design. Furthermore, the recent 2015 US Nuclear Science Long-Range Planning effort included a future EIC as a recommendation for future construction. The EIC will be unique in colliding polarised electrons off polarised protons and light nuclei, providing the spin degrees of freedom essential to pursue its physics program driven by spin structure, multi-dimensional tomographic images of protons and nuclei, and discovery of the role of collective effects of gluons in nuclei. The foreseen luminosity of the EIC,more » coupled with its energy variability and reach, will allow unprecedented three-dimensional imaging of the gluon and sea quark distributions, via both TMDs and GPDs, and to explore correlations amongst them. Its hermetic detection capability of correlated fragments promises to similar allow for precise tomographic images of the quark-gluon landscape in nuclei, transcending from light few-body nuclei to the heaviest nuclei, and could uncover how the TMD and GPD landscape changes when gluons display an anticipated collective behavior at the higher energies.« less

Suppressing relaxation in superconducting qubits by quasiparticle pumping.

PubMed

Gustavsson, Simon; Yan, Fei; Catelani, Gianluigi; Bylander, Jonas; Kamal, Archana; Birenbaum, Jeffrey; Hover, David; Rosenberg, Danna; Samach, Gabriel; Sears, Adam P; Weber, Steven J; Yoder, Jonilyn L; Clarke, John; Kerman, Andrew J; Yoshihara, Fumiki; Nakamura, Yasunobu; Orlando, Terry P; Oliver, William D

2016-12-23

Dynamical error suppression techniques are commonly used to improve coherence in quantum systems. They reduce dephasing errors by applying control pulses designed to reverse erroneous coherent evolution driven by environmental noise. However, such methods cannot correct for irreversible processes such as energy relaxation. We investigate a complementary, stochastic approach to reducing errors: Instead of deterministically reversing the unwanted qubit evolution, we use control pulses to shape the noise environment dynamically. In the context of superconducting qubits, we implement a pumping sequence to reduce the number of unpaired electrons (quasiparticles) in close proximity to the device. A 70% reduction in the quasiparticle density results in a threefold enhancement in qubit relaxation times and a comparable reduction in coherence variability. Copyright © 2016, American Association for the Advancement of Science.

Analysis of Voyager Observed High-Energy Electron Fluxes in the Heliosheath Using MHD Simulations

NASA Technical Reports Server (NTRS)

Washimi, Haruichi; Webber, W. R.; Zank, Gary P.; Hu, Qiang; Florinski, Vladimir; Adams, James; Kubo, Yuki

2011-01-01

The Voyager spacecraft (V1 and V2) observed electrons of 6-14 MeV in the heliosheath which showed several incidences of flux variation relative to a background of gradually increasing flux with distance from the Sun. The increasing flux of background electrons is thought to result from inward radial diffusion. We compare the temporal electron flux variation with dynamical phenomena in the heliosheath that are obtained from our MHD simulations. Because our simulation is based on V2 observed plasma data before V2 crossed the termination shock, this analysis is effective up to late 2008, i.e., about a year after the V2-crossing, during which disturbances, driven prior to the crossing time, survived in the heliosheath. Several electron flux variations correspond to times directly associated with interplanetary shock events. One noteworthy example corresponds to various times associated with the March 2006 interplanetary shock, these being the collision with the termination shock, the passage past the V1 spacecraft, and the collision with the region near the heliopause, as identified by W.R. Webber et al. for proton/helium of 7-200 MeV. Our simulations indicate that all other electron flux variations, except one, correspond well to the times when a shock-driven magneto-sonic pulse and its reflection in the heliosheath either passed across V1/V2, or collided with the termination shock or with the plasma sheet near the heliopause. This result suggests that variation in the electron flux should be due to either direct or indirect effects of magnetosonic pulses in the heliosheath driven by interplanetary shocks

Probing SEP Acceleration Processes With Near-relativistic Electrons

NASA Astrophysics Data System (ADS)

Haggerty, Dennis K.; Roelof, Edmond C.

2009-11-01

Processes in the solar corona are prodigious accelerators of near-relativistic electrons. Only a small fraction of these electrons escape the low corona, yet they are by far the most abundant species observed in Solar Energetic Particle events. These beam-like energetic electron events are sometimes time-associated with coronal mass ejections from the western solar hemisphere. However, a significant number of events are observed without any apparent association with a transient event. The relationship between solar energetic particle events, coronal mass ejections, and near-relativistic electron events are better ordered when we classify the intensity time profiles during the duration of the beam-like anisotropies into three broad categories: 1) Spikes (rapid and equal rise and decay) 2) Pulses (rapid rise, slower decay) and 3) Ramps (rapid rise followed by a plateau). We report on the results of a study that is based on our catalog (covering nearly the complete Solar Cycle 23) of 216 near-relativistic electron events and their association with: solar electromagnetic emissions, shocks driven by coronal mass ejections, models of the coronal magnetic fields and energetic protons. We conclude that electron events with time-intensity profiles of Spikes and Pulses are associated with explosive events in the low corona while events with time-intensity profiles of Ramps are associated with the injection/acceleration process of the CME driven shock.

Fano resonance in the nonadiabatically pumped shot noise of a time-dependent quantum well in a two-dimensional electron gas and graphene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Rui, E-mail: rzhu@scut.edu.cn; Dai, Jiao-Hua; Guo, Yong

Interference between different quantum paths can generate Fano resonance. One of the examples is transport through a quasibound state driven by a time-dependent scattering potential. Previously it is found that Fano resonance occurs as a result of energy matching in one-dimensional systems. In this work, we demonstrate that when transverse motion is present, Fano resonance occurs precisely at the wavevector matching situation. Using the Floquet scattering theory, we considered the transport properties of a nonadiabatic time-dependent well both in a two-dimensional electron gas and monolayer graphene structure. Dispersion of the quasibound state of a static quantum well is obtained withmore » transverse motion present. We found that Fano resonance occurs when the wavevector in the transport direction of one of the Floquet sidebands is exactly identical to that of the quasibound state in the well at equilibrium and follows the dispersion pattern of the latter. To observe the Fano resonance phenomenon in the transmission spectrum, we also considered the pumped shot noise properties when time and spatial symmetry secures vanishing current in the considered configuration. Prominent Fano resonance is found in the differential pumped shot noise with respect to the reservoir Fermi energy.« less

Design and optimization of a compact laser-driven proton beamline.

PubMed

Scisciò, M; Migliorati, M; Palumbo, L; Antici, P

2018-04-19

Laser-accelerated protons, generated by irradiating a solid target with a short, energetic laser pulse at high intensity (I > 10 18  W·cm -2 ), represent a complementary if not outperforming source compared to conventional accelerators, due  to their intrinsic features, such as high beam charge and short bunch duration. However, the broadband energy spectrum of these proton sources is a bottleneck that precludes their use in applications requiring a more reduced energy spread. Consequently, in recent times strong effort has been put to overcome these limits and to develop laser-driven proton beamlines with low energy spread. In this paper, we report on beam dynamics simulations aiming at optimizing a laser-driven beamline - i.e. a laser-based proton source coupled to conventional magnetic beam manipulation devices - producing protons with a reduced energy spread, usable for applications. The energy range of investigation goes from 2 to 20 MeV, i.e. the typical proton energies that can be routinely obtained using commercial TW-power class laser systems. Our beamline design is capable of reducing the energy spread below 20%, still keeping the overall transmission efficiency around 1% and producing a proton spot-size in the range of 10 mm 2 . We briefly discuss the results in the context of applications in the domain of Cultural Heritage.

Progress on FIR interferometry and Thomson Scattering measurements on HIT-SI3

NASA Astrophysics Data System (ADS)

Everson, Christopher; Jarboe, Thomas; Morgan, Kyle

2017-10-01

Spatially resolved measurements of the electron temperature (Te) and density (ne) will be fundamental in assessing the degree to which HIT-SI3 demonstrates closed magnetic flux and energy confinement. Further, electron temperature measurements have not yet been made on an inductively-driven spheromak. Far infrared (FIR) interferometer and Thomson Scattering (TS) systems have been installed on the HIT-SI3 spheromak. The TS system currently implemented on HIT-SI3 was originally designed for other magnetic confinement experiments, and progress continues toward modifying and optimizing for HIT-SI3 plasmas. Initial results suggest that the electron temperature is of order 10 eV. Plans to modify the TS system to provide more sensitivity and accuracy at low temperatures are presented. The line-integrated ne is measured on one chord by the FIR interferometer, with densities near 5x1019 m-3. Four cylindrical volumes have been added to the HIT-SI3 apparatus to enhance passive pumping. It is hoped that this will allow for more control of the density during the 2 ms discharges. Density measurements from before and after the installation of the passive pumping volumes are presented for comparison.

Development and Characterization of Titanium Dioxide Gel with Encapsulated Bacteriorhodopsin for Hydrogen Production.

PubMed

Johnson, Kaitlin E; Gakhar, Sukriti; Risbud, Subhash H; Longo, Marjorie L

2018-06-06

We study bacteriorhodopsin (BR) in its native purple membrane encapsulated within amorphous titanium dioxide, or titania, gels and in the presence of titania sol-particles to explore this system for hydrogen production. Förster resonance energy transfer between BR and titanium dioxide sol particles was used to conclude that there is nanometer-scale proximity of bacteriorhodopsin to the titanium dioxide. The detection of BR-titania sol aggregates by fluorescence anisotropy and particle sizing indicated the affinity amorphous titania has for BR without the use of additional cross-linkers. UV-Visible spectroscopy of BR-titania gels show that methanol addition did not denature BR at a 25 mM concentration presence as a sacrificial electron donor. Additionally, confinement of BR in the gels significantly limited protein denaturation at higher concentration of added methanol or ethanol. Subsequently, titania gels fabricated through the sol-gel process using a titanium ethoxide precursor, water and the addition of 25 mM methanol were used to encapsulate BR and a platinum reduction catalyst for the production of hydrogen gas under white light irradiation. The inclusion of 5 µM bacteriorhodopsin resulted in a hydrogen production rate of about 3.8 µmole hydrogen mL -1 hr -1 , an increase of 52% compared to gels containing no protein. Electron transfer and proton pumping by BR in close proximity to the titania gel surface are feasible explanations for the enhanced production of hydrogen without the need to crosslink BR to the titania gel. This work sets the stage for further developments of amorphous, rather than crystalline, titania-encapsulated bacteriorhodopsin for solar-driven hydrogen production through water-splitting.

Laser-driven proton and deuteron acceleration from a pure solid-density H2/D2 cryogenic jet

NASA Astrophysics Data System (ADS)

Kim, Jongjin; Gauthier, Maxence; Aurand, Bastian; Curry, Chandra; Goede, Sebastian; Goyon, Clement; Williams, Jackson; Kerr, Shaun; Ruby, John; Propp, Adrienne; Ramakrishna, Bhuvanesh; Pak, Art; Hazi, Andy; Glenzer, Siegfried; Roedel, Christian

2015-11-01

Laser-driven proton acceleration has become of tremendous interest for the fundamental science and the potential applications in tumor therapy and proton radiography. We have developed a cryogenic liquid hydrogen jet, which can deliver a self-replenishing target of pure solid-density hydrogen or deuterium. This allows for a target compatible with high-repetition-rate experiments and results in a pure hydrogen plasma, facilitating comparison with simulations. A new modification has allowed for the formation of jets with rectangular profiles, facilitating comparison with foil targets. This jet was installed at the Titan laser and driven by laser pulses of 40-60 J of 527 nm laser light in 1 ps. The resulting proton and deuteron spectra were measured in multiple directions with Thomson parabola spectrometers and RCF stacks. The spectral and angular information suggest contribution from both the TNSA and RPA acceleration mechanisms.

Fluoroquinolone resistance of Serratia marcescens: involvement of a proton gradient-dependent efflux pump.

PubMed

Kumar, Ayush; Worobec, Elizabeth A

2002-10-01

To determine the presence of a proton gradient-dependent efflux of fluoroquinolone drugs in Serratia marcescens. Thirteen clinical isolates of S. marcescens were screened for resistance to four fluoroquinolones: ofloxacin, ciprofloxacin, norfloxacin and nalidixic acid by determining MICs. The presence of a proton gradient-dependent efflux mechanism was assessed using ethidium bromide accumulation assays. Drug accumulation studies for norfloxacin, ciprofloxacin and ofloxacin were performed to determine the drug specificity of efflux. Western transfer of cellular proteins, followed by immunodetection using anti-AcrA (Escherichia coli) antibodies were used to demonstrate the presence of a resistance-nodulation-cell division (RND) pump protein. PCR was used to identify a RND pump-encoding gene using primers for two conserved motifs within inner membrane components of RND proteins. A mutant strain of S. marcescens, UOC-67WL, was isolated by culturing the wild-type strain in the presence of ciprofloxacin in T-soy media and was subjected to the same studies as described above for the clinical isolates. Ethidium bromide accumulation assays confirmed the presence of a proton gradient-dependent efflux mechanism in S. marcescens. One clinical isolate, T-861, and the mutant strain, UOC-67WL, were found to efflux ciprofloxacin and ofloxacin. Western immunoblot results confirmed overexpression of an AcrA-like protein in T-861 and UOC-67WL. Sequencing of the PCR product showed the presence of a mexF-like gene, which is overexpressed in nfxC mutants of Pseudomonas aeruginosa. This study reports the presence of a proton gradient-dependent efflux mechanism in S. marcescens.

Root bacterial endophytes confer drought resistance and enhance expression and activity of a vacuolar H+ -pumping pyrophosphatase in pepper plants.

PubMed

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.

Lactobacillus paracasei F19 versus placebo for the prevention of proton pump inhibitor-induced bowel symptoms: a randomized clinical trial.

PubMed

Compare, Debora; Rocco, Alba; Sgamato, Costantino; Coccoli, Pietro; Campo, Salvatore Maria Antonio; Nazionale, Immacolata; Larussa, Tiziana; Luzza, Francesco; Chiodini, Paolo; Nardone, Gerardo

2015-04-01

Proton pump inhibitors may foster intestinal dysbiosis and related bowel symptoms. To evaluate the effect of Lactobacillus paracasei F19 on bowel symptom onset in patients on long-term proton pump inhibitors. In this randomized, double-blind, placebo-controlled study, patients with typical gastroesophageal reflux disease symptoms receiving pantoprazole 40 mg/d for six months were randomly assigned to receive: (A) Lactobacillus paracasei F19 bid for three days/week for six months; (B) placebo bid for three days/week for six months; (C) Lactobacillus paracasei F19 bid for three days/week for three months and placebo bid for three days/week for the following three months; (D) placebo bid for three days/week for three months and Lactobacillus paracasei F19 bid for three days/week for the following three months. Bloating, flatulence, abdominal pain and bowel habit were assessed monthly. 100/312 patients were enrolled. In the parallel groups, the treatment-by-time interaction affected bloating (p = 0.015), while Lactobacillus paracasei F19 treatment alone affected flatulence (p = 0.011). Moreover, the treatment-by-time interaction significantly affected the mean score of bloating (p = 0.01) and flatulence (p < 0.0001), the mean stool form (p = 0.03) and mean stool frequency/week (p = 0.016). Analysis of the cross-over groups, limited to the first three months because of carry-over effect, confirmed these results. Lactobacillus paracasei F19 supplementation prevents bowel symptom onset in patients on long-term proton pump inhibitors. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case-control study

PubMed Central

Vonkeman, Harald E; Fernandes, Robert W; van der Palen, Job; van Roon, Eric N; van de Laar, Mart AFJ

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. Selective cyclooxygenase-2 (COX-2) inhibitors reduce the risk for ulcer complications, but not completely in high-risk patients. This study determines which patients are especially at risk for NSAID ulcer complications and investigates the effectiveness of different preventive strategies in daily clinical practice. With the use of a nested case-control design, a large cohort of NSAID users was followed for 26 months. Cases were patients with NSAID ulcer complications necessitating hospitalisation; matched controls were selected from the remaining cohort of NSAID users who did not have NSAID ulcer complications. During the observational period, 104 incident cases were identified from a cohort of 51,903 NSAID users with 10,402 patient years of NSAID exposure (incidence 1% per year of NSAID use, age at diagnosis 70.4 ± 16.7 years (mean ± SD), 55.8% women), and 284 matched controls. Cases were characterised by serious, especially cardiovascular, co-morbidity. In-hospital mortality associated with NSAID ulcer complications was 10.6% (incidence 21.2 per 100,000 NSAID users). Concomitant proton-pump inhibitors (but not selective COX-2 inhibitors) were associated with a reduced risk for NSAID ulcer complications (the adjusted odds ratio 0.33; 95% confidence interval 0.17 to 0.67; p = 0.002). Especially at risk for NSAID ulcer complications are elderly patients with cardiovascular co-morbidity. Proton-pump inhibitors are associated with a reduced risk for NSAID ulcer complications. PMID:17521422

Proton pump inhibitors are associated with increased risk of development of chronic kidney disease.

PubMed

Arora, Pradeep; Gupta, Anu; Golzy, Mojgan; Patel, Nilang; Carter, Randolph L; Jalal, Kabir; Lohr, James W

2016-08-03

Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death. Two separate retrospective case-control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables. A total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case-control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05-1.16) and mortality (OR 1.76, 95 % CI 1.67-1.84) among patients taking PPIs versus those not on PPIs. Use of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications.

A study on various methods of supplying propellant to an orbit insertion rocket engine

NASA Technical Reports Server (NTRS)

Boretz, J. E.; Huniu, S.; Thompson, M.; Pagani, M.; Paulsen, B.; Lewis, J.; Paul, D.

1980-01-01

Various types of pumps and pump drives were evaluated to determine the lightest weight system for supplying propellants to a planetary orbit insertion rocket engine. From these analyses four candidate propellant feed systems were identified. Systems Nos. 1 and 2 were both battery powered (lithium-thionyl-chloride or silver-zinc) motor driven pumps. System 3 was a monopropellant gas generator powered turbopump. System 4 was a bipropellant gas generator powered turbopump. Parameters considered were pump break horsepower, weight, reliability, transient response and system stability. Figures of merit were established and the ranking of the candidate systems was determined. Conceptual designs were prepared for typical motor driven pumps and turbopump configurations for a 1000 lbf thrust rocket engine.

Development of a miniature motor-driven pulsatile LVAD driven by a fuzzy controller.

PubMed

Okamoto, Eiji; Makino, Tsutomu; Tanaka, Shuji; Yasuda, Takahiko; Akasaka, Yuta; Tani, Makiko; Inoue, Yusuke; Mitoh, Ayumu; Mitamura, Yoshinori

2007-01-01

We have been developing a small, lightweight motor-driven pulsatile left ventricular assist device (LVAD) with a ball screw. The motor-driven LVAD consists of a brushless DC motor and a ball screw. The attractive magnetic force between Nd-Fe-B magnets (with a diameter of 5 mm and a thickness of 1.5 mm) mounted in holes in a silicone rubber sheet (thickness 2 mm) and an iron plate adhered onto the a diaphragm of the blood pump can provide optimum active blood filling during the pump filling phase. The LVAD has a stroke volume of 55 ml and an overall volume of 285 ml; it weighs 360 g. The controller mainly consists of a fuzzy logic position and velocity controller to apply doctors' and engineers' knowledge to control the LVAD. Each unit of the controller consists of a functionally independent program module for easy improvement of the controller's performance. The LVAD was evaluated in in vitro experiments using a mock circulation. A maximum pump outflow of 5.1 l/min was obtained at a drive rate of 95 bpm against an afterload of 95 mmHg, and active filling using the attractive magnetic force provided a pump output of 3.6 l/min at a drive rate of 75 bpm under a preload of 0 mmHg. The operating efficiency of the LVAD was measured at between 8% and 10.5%. While the LVAD can provide adequate pump outflow for cardiac assistance, further upgrading of the software and improvement of the blood pump are required to improve pump performance and efficiency.

An evaluation of a hubless inducer and a full flow hydraulic turbine driven inducer boost pump

NASA Technical Reports Server (NTRS)

Lindley, B. K.; Martinson, A. R.

1971-01-01

The purpose of the study was to compare the performance of several configurations of hubless inducers with a hydrodynamically similar conventional inducer and to demonstrate the performance of a full flow hydraulic turbine driven inducer boost pump using these inducers. A boost pump of this type consists of an inducer connected to a hydraulic turbine with a high speed rotor located in between. All the flow passes through the inducer, rotor, and hydraulic turbine, then into the main pump. The rotor, which is attached to the main pump shaft, provides the input power to drive the hydraulic turbine which, in turn, drives the inducer. The inducer, rotating at a lower speed, develops the necessary head to prevent rotor cavitation. The rotor speed is consistent with present main engine liquid hydrogen pump designs and the overall boost pump head rise is sufficient to provide adequate main pump suction head. This system would have the potential for operating at lower liquid hydrogen tank pressures.

Presence of a plant-like proton-pumping pyrophosphatase in acidocalcisomes of Trypanosoma cruzi.

PubMed

Scott, D A; de Souza, W; Benchimol, M; Zhong, L; Lu, H G; Moreno, S N; Docampo, R

1998-08-21

The vacuolar-type proton-translocating pyrophosphatase (V-H+-PPase) is an enzyme previously described in detail only in plants. This paper demonstrates its presence in the trypanosomatid Trypanosoma cruzi. Pyrophosphate promoted organellar acidification in permeabilized amastigotes, epimastigotes, and trypomastigotes of T. cruzi. This activity was stimulated by K+ ions and was inhibited by Na+ ions and pyrophosphate analogs, as is the plant activity. Separation of epimastigote extracts on Percoll gradients yielded a dense fraction that contained H+-PPase activity measured both by proton uptake and phosphate release but lacked markers for mitochondria, lysosomes, glycosomes, cytosol, and plasma membrane. Antiserum raised against specific sequences of the plant V-H+-PPase cross-reacted with a T. cruzi protein, which was also detectable in the dense Percoll fraction. The organelles in this fraction appeared by electron microscopy to consist mainly of acidocalcisomes (acidic calcium storage organelles). This identification was confirmed by x-ray microanalysis. Immunofluorescence and immunoelectron microscopy indicated that the V-H+-PPase was located in the plasma membrane and acidocalcisomes of the three different forms of the parasite. Pyrophosphate was able to drive calcium uptake in permeabilized T. cruzi. This uptake depended upon a proton gradient and was reversed by a specific V-H+-PPase inhibitor. Our results imply that the phylogenetic distribution of V-H+-PPases is much wider than previously perceived but that the enzyme has a unique subcellular location in trypanosomes.

Effect of high energy electrons on H{sup −} production and destruction in a high current DC negative ion source for cyclotron

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onai, M., E-mail: onai@ppl.appi.keio.ac.jp; Fujita, S.; Hatayama, A.

2016-02-15

Recently, a filament driven multi-cusp negative ion source has been developed for proton cyclotrons in medical applications. In this study, numerical modeling of the filament arc-discharge source plasma has been done with kinetic modeling of electrons in the ion source plasmas by the multi-cusp arc-discharge code and zero dimensional rate equations for hydrogen molecules and negative ions. In this paper, main focus is placed on the effects of the arc-discharge power on the electron energy distribution function and the resultant H{sup −} production. The modelling results reasonably explains the dependence of the H{sup −} extraction current on the arc-discharge powermore » in the experiments.« less

Packaged peristaltic micropump for controlled drug delivery application

NASA Astrophysics Data System (ADS)

Vinayakumar, K. B.; Nadiger, Girish; R. Shetty, Vikas; Dinesh, N. S.; Nayak, M. M.; Rajanna, K.

2017-01-01

Micropump technology has evolved significantly in the last two decades and is finding a variety of applications ranging from μTAS (micro Total Analysis System) to drug delivery. However, the application area of the micropump is limited owing to: simple pumping mechanism, ease of handling, controlled (microliter to milliliter) delivery, continuous delivery, and accuracy in flow rate. Here, the author presents the design, development, characterization, and precision flow controlling of a DC-motor driven peristaltic pump for controlled drug delivery application. All the micropump components were fabricated using the conventional fabrication technique. The volume flow variation of the pump has been characterized for different viscous fluids. The change in volume flow due to change in back pressure has been presented in detail. The fail-safe mode operation of the pump has been tested and leak rate was measured (˜0.14% leak for an inlet pressure of 140 kPa) for different inlet pressures. The precision volume flow of the pump has been achieved by measuring the pinch cam position and load current. The accuracy in the volume flow has been measured after 300 rotations. Finally, the complete system has been integrated with the necessary electronics and an android application has been developed for the self-administration of bolus and basal delivery of insulin.

Realistic simulations of the coupling between the protomotive force and the mechanical rotation of the F0-ATPase

PubMed Central

Mukherjee, Shayantani; Warshel, Arieh

2012-01-01

The molecular origin of the action of the F0 proton gradient-driven rotor presents a major puzzle despite significant structural advances. Although important conceptual models have provided guidelines of how such systems should work, it has been challenging to generate a structure-based molecular model using physical principles that will consistently lead to the unidirectional proton-driven rotational motion during ATP synthesis. This work uses a coarse-grained (CG) model to simulate the energetics of the F0-ATPase system in the combined space defined by the rotational coordinate and the proton transport (PTR) from the periplasmic side (P) to the cytoplasmic side (N). The model establishes the molecular origin of the rotation, showing that this effect is due to asymmetry in the energetics of the proton path rather than only the asymmetry of the interaction of the Asp on the c-ring helices and Arg on the subunit-a. The simulation provides a clear conceptual background for further exploration of the electrostatic basis of proton-driven mechanochemical systems. PMID:22927379

Probing short-range correlations in asymmetric nuclei with quasi-free pair knockout reactions

NASA Astrophysics Data System (ADS)

Stevens, Sam; Ryckebusch, Jan; Cosyn, Wim; Waets, Andreas

2018-02-01

Short-range correlations (SRC) in asymmetric nuclei with an unusual neutron-to-proton ratio can be studied with quasi-free two-nucleon knockout processes following the collision between accelerated ions and a proton target. We derive an approximate factorized cross section for those SRC-driven p (A ,p‧N1N2) reactions. Our reaction model hinges on the factorization properties of SRC-driven A (e ,e‧N1N2) reactions for which strong indications are found in theory-experiment comparisons. In order to put our model to the test we compare its predictions with results of 12C (p ,p‧ pn) measurements conducted at Brookhaven National Laboratory (BNL) and find a fair agreement. The model can also reproduce characteristic features of SRC-driven two-nucleon knockout reactions, like back-to-back emission of the correlated nucleons. We study the asymmetry dependence of nuclear SRC by providing predictions for the ratio of proton-proton to proton-neutron knockout cross sections for the carbon isotopes 9-15C thereby covering neutron excess values (N - Z) / Z between -0.5 and +0.5.

Vapor cycle energy system for implantable circulatory assist devices. Annual progress report Jul 1974--Jun 1975. [Tidal regenerator engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hagen, K.G.

1975-06-01

The report describes the development status of a heart assist system driven by a nuclear fueled, electronically controlled vapor cycle engine termed the tidal regenerator engine (TRE). The TRE pressurization (typically from 5-160 psia) is controlled by a torque motor coupled to a displacer. The electrical power for the sensor, electronic logic and actuator is provided by a thermoelectric module interposed between the engine superheater and boiler. The TRE is direct coupled to an assist blood pump which also acts as a blood-cooled heat exchanger, pressure-volume transformer and sensor for the electronic logic. Engine efficiencies in excess of 14% havemore » been demonstrated. Efficiency values as high as 13% have been achieved to date.« less

Dielectric Yagi-Uda nanoantennas driven by electron-hole plasma photoexcitation

NASA Astrophysics Data System (ADS)

Li, S.; Lepeshov, S.; Savelev, R.; Baranov, D.; Belov, P.; Krasnok, A.

2017-11-01

All-dielectric nanophotonics based on high-index dielectric nanoparticles became a powerful platform for modern light science, providing many fascinating applications, including high-efficient nanoantennas and metamaterials. High-index dielectric nanostructures are of a special interest for nonlinear nanophotonics, where they demonstrate special types of optical nonlinearity, such as electron-hole plasma photoexcitation, which are not inherent to plasmonic nanostructures. Here, we propose a novel type of highly tunable all-dielectric Yagi-Uda nanoantennas, consisting of a chain of Si nanoparticles exciting by an electric dipole source, which allow tuning of their radiating properties via electron-hole plasma photoexcitation. We theoretically and numerically demonstrate the tuning of radiation power patterns and the Purcell effect by additional pumping of several boundary nanoparticles with relatively low peak intensities of fs-laser.

46 CFR 185.512 - Recommended emergency instructions format.

Code of Federal Regulations, 2011 CFR

2011-10-01

... in bilges. Use power driven bilge pump, hand pump, and buckets to dewater. (iii) Align fire pumps to... fixed extinguishing system if installed. (v) Maneuver vessel to minimize effect of wind on fire. (vi) If...

Hypomagnesaemia associated with long-term use of proton pump inhibitors

PubMed Central

Toh, James Wei Tatt; Ong, Evonne; Wilson, Robert

2015-01-01

Hypomagnesaemia and associated hypocalcaemia and hypoparathyroidism have been increasingly recognised as rare long-term side-effects of proton pump inhibitors (PPIs). The PPIs may inhibit active magnesium (Mg) absorption by interfering with transcellular transient receptor potential melastatin-6 and -7 (TRPM 6 and 7) channels. More recent cell culture studies have suggested concomitant inhibition of passive Mg absorption by omeprazole. After being treated with a range of PPIs, the four patients in our case series developed hypomagnesaemia, which responded to withdrawal of therapy and initiation of Mg replacement. Their clinical course and management demonstrate key aspects of hypomagnesaemia associated with long-term use of PPIs. PMID:25138239