Measurement of the underlying event activity using charged-particle jets in proton-proton collisions at $$\\sqrt{s}$$ = 2.76 TeV

DOE PAGES

Khachatryan, V.

2015-09-21

A measurement of the underlying event (UE) activity in proton-proton collisions is performed using events with charged-particle jets produced in the central pseudorapidity region (|η jet| < 2) and with transverse momentum 1 ≤ p T jet < 100 GeV. The analysis uses a data sample collected at a centre-of-mass energy of 2.76 TeV with the CMS experiment at the LHC. The UE activity is measured as a function of p T jet in terms of the average multiplicity and scalar sum of transverse momenta (p T) of charged particles, with |η| < 2 and p T >more » 0.5 GeV, in the azimuthal region transverse to the highest p T jet direction. By further dividing the transverse region into two regions of smaller and larger activity, various components of the UE activity are separated. As a result, the measurements are compared to previous results at 0.9 and 7 TeV, and to predictions of several Monte Carlo event generators, providing constraints on the modelling of the UE dynamics« less

Visualizing the kinetic power stroke that drives proton-coupled Zn(II) transport

PubMed Central

Gupta, Sayan; Chai, Jin; Cheng, Jie; D'Mello, Rhijuta; Chance, Mark R.; Fu, Dax

2014-01-01

The proton gradient is a principal energy source for respiration-dependent active transport, but the structural mechanisms of proton-coupled transport processes are poorly understood. YiiP is a proton-coupled zinc transporter found in the cytoplasmic membrane of E. coli, and the transport-site of YiiP receives protons from water molecules that gain access to its hydrophobic environment and transduces the energy of an inward proton gradient to drive Zn(II) efflux1,2. This membrane protein is a well characterized member3-7 of the protein family of cation diffusion facilitators (CDFs) that occurs at all phylogenetic levels8-10. X-ray mediated hydroxyl radical labeling of YiiP and mass spectrometric analysis showed that Zn(II) binding triggered a highly localized, all-or-none change of water accessibility to the transport-site and an adjacent hydrophobic gate. Millisecond time-resolved dynamics revealed a concerted and reciprocal pattern of accessibility changes along a transmembrane helix, suggesting a rigid-body helical reorientation linked to Zn(II) binding that triggers the closing of the hydrophobic gate. The gated water access to the transport-site enables a stationary proton gradient to facilitate the conversion of zinc binding energy to the kinetic power stroke of a vectorial zinc transport. The kinetic details provide energetic insights into a proton-coupled active transport reaction. PMID:25043033

Perfluoroalkyl phosphonic and phosphinic acids as proton conductors for anhydrous proton-exchange membranes.

PubMed

Herath, Mahesha B; Creager, Stephen E; Kitaygorodskiy, Alex; DesMarteau, Darryl D

2010-09-10

A study of proton-transport rates and mechanisms under anhydrous conditions using a series of acid model compounds, analogous to comb-branch perfluorinated ionomers functionalized with phosphonic, phosphinic, sulfonic, and carboxylic acid protogenic groups, is reported. Model compounds are characterized with respect to proton conductivity, viscosity, proton, and anion (conjugate base) self-diffusion coefficients, and Hammett acidity. The highest conductivities, and also the highest viscosities, are observed for the phosphonic and phosphinic acid model compounds. Arrhenius analysis of conductivity and viscosity for these two acids reveals much lower activation energies for ion transport than for viscous flow. Additionally, the proton self-diffusion coefficients are much higher than the conjugate-base self-diffusion coefficients for these two acids. Taken together, these data suggest that anhydrous proton transport in the phosphonic and phosphinic acid model compounds occurs primarily by a structure-diffusion, hopping-based mechanism rather than a vehicle mechanism. Further analysis of ionic conductivity and ion self-diffusion rates by using the Nernst-Einstein equation reveals that the phosphonic and phosphinic acid model compounds are relatively highly dissociated even under anhydrous conditions. In contrast, sulfonic and carboxylic acid-based systems exhibit relatively low degrees of dissociation under anhydrous conditions. These findings suggest that fluoroalkyl phosphonic and phosphinic acids are good candidates for further development as anhydrous, high-temperature proton conductors.

Faster proton transfer dynamics of water on SnO2 compared to TiO2.

PubMed

Kumar, Nitin; Kent, Paul R C; Bandura, Andrei V; Kubicki, James D; Wesolowski, David J; Cole, David R; Sofo, Jorge O

2011-01-28

Proton jump processes in the hydration layer on the iso-structural TiO(2) rutile (110) and SnO(2) cassiterite (110) surfaces were studied with density functional theory molecular dynamics. We find that the proton jump rate is more than three times faster on cassiterite compared with rutile. A local analysis based on the correlation between the stretching band of the O-H vibrations and the strength of H-bonds indicates that the faster proton jump activity on cassiterite is produced by a stronger H-bond formation between the surface and the hydration layer above the surface. The origin of the increased H-bond strength on cassiterite is a combined effect of stronger covalent bonding and stronger electrostatic interactions due to differences of its electronic structure. The bridging oxygens form the strongest H-bonds between the surface and the hydration layer. This higher proton jump rate is likely to affect reactivity and catalytic activity on the surface. A better understanding of its origins will enable methods to control these rates.

Hybrid Quantum/Classical Molecular Dynamics Simulations of the Proton Transfer Reactions Catalyzed by Ketosteroid Isomerase: Analysis of Hydrogen Bonding, Conformational Motions, and Electrostatics

PubMed Central

Chakravorty, Dhruva K.; Soudackov, Alexander V.; Hammes-Schiffer, Sharon

2009-01-01

Hybrid quantum/classical molecular dynamics simulations of the two proton transfer reactions catalyzed by ketosteroid isomerase are presented. The potential energy surfaces for the proton transfer reactions are described with the empirical valence bond method. Nuclear quantum effects of the transferring hydrogen increase the rates by a factor of ~8, and dynamical barrier recrossings decrease the rates by a factor of 3–4. For both proton transfer reactions, the donor-acceptor distance decreases substantially at the transition state. The carboxylate group of the Asp38 side chain, which serves as the proton acceptor and donor in the first and second steps, respectively, rotates significantly between the two proton transfer reactions. The hydrogen bonding interactions within the active site are consistent with the hydrogen bonding of both Asp99 and Tyr14 to the substrate. The simulations suggest that a hydrogen bond between Asp99 and the substrate is present from the beginning of the first proton transfer step, whereas the hydrogen bond between Tyr14 and the substrate is virtually absent in the first part of this step but forms nearly concurrently with the formation of the transition state. Both hydrogen bonds are present throughout the second proton transfer step until partial dissociation of the product. The hydrogen bond between Tyr14 and Tyr55 is present throughout both proton transfer steps. The active site residues are more mobile during the first step than during the second step. The van der Waals interaction energy between the substrate and the enzyme remains virtually constant along the reaction pathway, but the electrostatic interaction energy is significantly stronger for the dienolate intermediate than for the reactant and product. Mobile loop regions distal to the active site exhibit significant structural rearrangements and, in some cases, qualitative changes in the electrostatic potential during the catalytic reaction. These results suggest that relatively small conformational changes of the enzyme active site and substrate strengthen the hydrogen bonds that stabilize the intermediate, thereby facilitating the proton transfer reactions. Moreover, the conformational and electrostatic changes associated with these reactions are not limited to the active site but rather extend throughout the entire enzyme. PMID:19799395

Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.

PubMed

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

2015-09-15

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

Catalogue of 55-80 MeV solar proton events extending through solar cycles 23 and 24

NASA Astrophysics Data System (ADS)

Paassilta, Miikka; Raukunen, Osku; Vainio, Rami; Valtonen, Eino; Papaioannou, Athanasios; Siipola, Robert; Riihonen, Esa; Dierckxsens, Mark; Crosby, Norma; Malandraki, Olga; Heber, Bernd; Klein, Karl-Ludwig

2017-06-01

We present a new catalogue of solar energetic particle events near the Earth, covering solar cycle 23 and the majority of solar cycle 24 (1996-2016), based on the 55-80 MeV proton intensity data gathered by the Solar and Heliospheric Observatory/the Energetic and Relativistic Nuclei and Electron experiment (SOHO/ERNE). In addition to ERNE proton and heavy ion observations, data from the Advanced Composition Explorer/Electron, Proton and Alpha Monitor (ACE/EPAM) (near-relativistic electrons), SOHO/EPHIN (Electron Proton Helium Instrument) (relativistic electrons), SOHO/LASCO (Large Angle and Spectrometric Coronagraph) (coronal mass ejections, CMEs) and Geostationary Operational Environmental Satellite (GOES) soft X-ray experiments are also considered and the associations between the particle and CME/X-ray events deduced to obtain a better understanding of each event. A total of 176 solar energetic particle (SEP) events have been identified as having occurred during the time period of interest; their onset and solar release times have been estimated using both velocity dispersion analysis (VDA) and time-shifting analysis (TSA) for protons, as well as TSA for near-relativistic electrons. Additionally, a brief statistical analysis was performed on the VDA and TSA results, as well as the X-rays and CMEs associated with the proton/electron events, both to test the viability of the VDA and to investigate possible differences between the two solar cycles. We find, in confirmation of a number of previous studies, that VDA results for protons that yield an apparent path length of 1 AU < s ≾ 3 AU seem to be useful, but those outside this range are probably unreliable, as evidenced by the anticorrelation between apparent path length and release time estimated from the X-ray activity. It also appears that even the first-arriving energetic protons apparently undergo significant pitch angle scattering in the interplanetary medium, with the resulting apparent path length being on average about twice the length of the spiral magnetic field. The analysis indicates an increase in high-energy SEP events originating from the far-eastern solar hemisphere; for instance, such an event with a well-established associated GOES flare has so far occurred three times during cycle 24 but possibly not at all during cycle 23. The generally lower level of solar activity during cycle 24, as opposed to cycle 23, has probably caused a significant decrease in total ambient pressure in the interplanetary space, leading to a larger proportion of SEP-associated halo-type CMEs. Taken together, these observations point to a qualitative difference between the two solar cycles.

Conformational flexibility of arginine-82 as source for the heterogeneous and pH-dependent kinetics of the primary proton transfer step in the bacteriorhodopsin photocycle: An electrostatic model

NASA Astrophysics Data System (ADS)

Scharnagl, Christina; Fischer, Sighart F.

1996-11-01

We use equilibrium thermodynamic concepts to relate protein conformational and protonation substates and their pH-dependent population to kinetic schemes for the rise of the M intermediate in the photocycle of bacteriorhodopsin. Conformational flexibility of arginine R82 is described by a two-state model. The analysis accounts for the electrostatic coupling between its orientation and hydrogen ion titration and presents a structural basis for the linkage between the protonation states of the primary proton acceptor, aspartate D85, and the extracellular release group, glutamate E204. We find that the charge state of D85 is a significant determinant for the orientation of R82. The molecular model predicts the following: the primary proton transfer to D85 can be described by a kinetic scheme with two heterogeneous substates. They control the event with different activation parameters due to the reorientation of R82 away from the chromophore binding site. Their population depends on the external pH and the proton exchange equilibrium between the membrane buried residues and the bulk aqueous solvent. Proton transfer in the physiologic pH range is strongly activated and followed by the reorientation of R82 which shifts the equilibrium toward complete transfer. In the alkaline pH region a different mechanism operates, which involves the increased population of a substate with already reoriented R82 as a consequence of the deprotonation of E204, leading to accelerated proton transfer. Assuming full proton exchange equilibrium with the bulk water on the millisecond time scale leads to an increased population of substates which are non-productive for proton transfer.

Study on strontium isotope abundance-ratio measurements by using a 13-MeV proton beam

NASA Astrophysics Data System (ADS)

Jeong, Cheol-Ki; Jang, Han; Lee, Goung-Jin

2016-09-01

The Rb-Sr dating method is used in dating Paleozoic and Precambrian rocks. This method measures the 87Rb and the 87Sr concentrations by using thermal ionization mass spectrometry (TIMS) [J. Hefne et al., Inter. J. Phys. Sci. 3(1), 28 (2008)]. In addition, it calculates the initial 87Sr/86Sr ratio to increase the reliability of Rb-Sr dating. In this study, the 87Sr/86Sr ratio was measured by using a 13-MeV proton accelerator. Proton kinetic energies are in the range of tens of megaelectronvolts, and protons have large absorption cross-sections for ( p, n) reactions with most substances. After absorbing a proton with such a high kinetic energy, an element is converted into a nuclide with its atomic number increased by one via nuclear transmutation. These nuclides usually have short half-lives and return to the original state through radioactive decay. When a strontium sample is irradiated with protons, nuclear transmutation occurs; thus, the strontium isotope present in the sample changes to a yttrium isotope, which is an activated radioisotope. Based on this, the 87Sr/86Sr ratio was calculated by analyzing the gamma-rays emitted by each yttrium isotope. The KIRAMS-13 cyclotron at the Cyclotron Center of Chosun University, where 13-MeV protons can be extracted, was utilized in our experiment. The 87Sr/86Sr isotope ratio was computed for samples irradiated with these protons, and the result was similar to the isotope ratio for the Standard Reference Material, i.e., 98.2 ± 3.4%. As part of the analysis, proton activation analyses were performed using 13-MeV protons, and the experimental results of this research suggest a possible approach for measuring the strontium-isotope abundance ratio of samples.

Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling

PubMed Central

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

2015-01-01

Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system. PMID:26370138

Solar proton fluxes since 1956. [sunspot activity correlation

NASA Technical Reports Server (NTRS)

Reedy, R. C.

1977-01-01

The fluxes of protons emitted during solar flares since 1956 were evaluated. The depth-versus-activity profiles of Co-56 in several lunar rocks are consistent with the solar proton fluxes detected by experiments on several satellites. Only about 20% of the solar-proton-induced activities of Na-22 and Fe-55 in lunar rocks from early Apollo missions were produced by protons emitted from the sun during solar cycle 20 (1965-1975). The depth-versus-activity data for these radionuclides in several lunar rocks were used to determine the fluxes of protons during solar cycle 19 (1954-1964). The average proton fluxes for cycle 19 are about five times those for both the last million years and for cycle 20 and are about five times the previous estimate for cycle 19 based on neutron-monitor and radio ionospheric measurements. These solar-proton flux variations correlate with changes in sunspot activity.

FTIR Study of the Photoactivation Process of Xenopus (6-4) Photolyase†

PubMed Central

Yamada, Daichi; Zhang, Yu; Iwata, Tatsuya; Hitomi, Kenichi; Getzoff, Elizabeth D.; Kandori, Hideki

2012-01-01

Photolyases (PHRs) are blue-light activated DNA repair enzymes that maintain genetic integrity by reverting UV-induced photoproducts into normal bases. The FAD chromophore of PHRs has four different redox states: oxidized (FADox), anion radical (FAD•−), neutral radical (FADH•) and fully reduced (FADH−). We combined difference Fourier-transform infrared (FTIR) spectroscopy with UV-visible spectroscopy to study the detailed photoactivation process of Xenopus (6-4) PHR. Two photons produce the enzymatically active, fully reduced PHR from oxidized FAD: FADox is converted to semiquinone via light-induced one-electron and one-proton transfers, and then to FADH− by light-induced one-electron transfer. We successfully trapped FAD•− at 200 K, where electron transfer occurs, but proton transfer does not. UV-visible spectroscopy following 450-nm illumination of FADox at 277 K defined the FADH•/FADH− mixture and allowed calculation of difference FTIR spectra among the four redox states. The absence of a characteristic C=O stretching vibration indicated that the proton donor is not a protonated carboxylic acid. Structural changes in Trp and Tyr are suggested from UV-visible and FTIR analysis of FAD•− at 200 K. Spectral analysis of amide-I vibrations revealed structural perturbation of the protein’s β-sheet during initial electron transfer (FAD•− formation), transient increase in α-helicity during proton transfer (FADH• formation) and reversion to the initial amide-I signal following subsequent electron transfer (FADH− formation). Consequently, in (6-4) PHR, unlike cryptochrome-DASH, formation of enzymatically active FADH− did not perturb α-helicity. Protein structural changes in the photoactivation of (6-4) PHR are discussed on the basis of the present FTIR observations. PMID:22747528

Quantifying Low Energy Proton Damage in Multijunction Solar Cells

NASA Technical Reports Server (NTRS)

Messenger, Scott R.; Burke, Edward A.; Walters, Robert J.; Warner, Jeffrey H.; Summers, Geoffrey P.; Lorentzen, Justin R.; Morton, Thomas L.; Taylor, Steven J.

2007-01-01

An analysis of the effects of low energy proton irradiation on the electrical performance of triple junction (3J) InGaP2/GaAs/Ge solar cells is presented. The Monte Carlo ion transport code (SRIM) is used to simulate the damage profile induced in a 3J solar cell under the conditions of typical ground testing and that of the space environment. The results are used to present a quantitative analysis of the defect, and hence damage, distribution induced in the cell active region by the different radiation conditions. The modelling results show that, in the space environment, the solar cell will experience a uniform damage distribution through the active region of the cell. Through an application of the displacement damage dose analysis methodology, the implications of this result on mission performance predictions are investigated.

SU-E-T-666: Radionuclides and Activity of the Patient Apertures Used in a Proton Beam of Wobbling System

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

Wang, B.Y.; Chen, H.H.; Tsai, H.Y.

2015-06-15

Purpose: To identify the radionuclides and quantify the activity of the patient apertures used in a 190-MeV proton beam of wobbling system. Methods: A proton beam of wobbling system in the first proton center in Taiwan, Chang Gung Memorial Hospital at Linkou, was used to bombard the patient apertures. The patient aperture was composed of 60.5 % copper, 39.4 % Zinc, 0.05 % iron, 0.05 % lead. A protable high-purity germanium (HPGe) coaxial detector was used to measure the spectra of the induced nuclides of patient apertures. The analysis of the spectra and the identification of the radionuclides were preliminarilymore » operated by the Nuclide Navigator III Master Library. On the basis of the results by Nuclide Navigator III Master Library, we manually selected the reliable nuclides by the gamma-ray energies, branching ratio, and half life. In the spectra, we can quantify the activity of radionuclides by the Monte Carlo efficiency transfer method. Results: In this study, the radioisotopes activated in patient apertures by the 190-MeV proton beam were divided into two categories. The first category is long half-life radionuclides, such as Co-56 (half life, 77.3 days). Other radionuclides of Cu-60, Cu-61, Cu-62, Cu-66, and Zn-62 have shorter half life. The radionuclide of Cu-60 had the highest activity. From calculation with the efficiency transfer method, the deviations between the computed results and the measured efficiencies were mostly within 10%. Conclusion: To identify the radionuclides and quantify the activity helps us to estimate proper time intervals for cooling the patient apertures. This study was supported by the grants from the Chang Gung Memorial Hospital (CMRPD1C0682)« less

Activation of a water molecule using a mononuclear Mn complex: from Mn-aquo, to Mn-hydroxo, to Mn-oxyl via charge compensation†

PubMed Central

Lassalle-Kaiser, Benedikt; Hureau, Christelle; Pantazis, Dimitrios A.; Pushkar, Yulia; Guillot, Régis; Yachandra, Vittal K.; Yano, Junko; Neese, Frank; Anxolabéhère-Mallart, Elodie

2014-01-01

Activation of a water molecule by the electrochemical oxidation of a Mn-aquo complex accompanied by the loss of protons is reported. The sequential (2 × 1 electron/1 proton) and direct (2 electron/2 proton) proton-coupled electrochemical oxidation of a non-porphyrinic six-coordinated Mn(II)OH2 complex into a mononuclear Mn(O) complex is described. The intermediate Mn(III)OH2 and Mn(III)OH complexes are electrochemically prepared and analysed. Complete deprotonation of the coordinated water molecule in the Mn(O) complex is confirmed by electrochemical data while the analysis of EXAFS data reveals a gradual shortening of an Mn–O bond upon oxidation from Mn(II)OH2 to Mn(III)OH and Mn(O). Reactivity experiments, DFT calculations and XANES pre-edge features provide strong evidence that the bonding in Mn(O) is best characterized by a Mn(III)-oxyl description. Such oxyl species could play a crucial role in natural and artificial water splitting reactions. We provide here a synthetic example for such species, obtained by electrochemical activation of a water ligand. PMID:24772190

Activation of a water molecule using a mononuclear Mn complex: from Mn-aquo, to Mn-hydroxo, to Mn-oxyl via charge compensation.

PubMed

Lassalle-Kaiser, Benedikt; Hureau, Christelle; Pantazis, Dimitrios A; Pushkar, Yulia; Guillot, Régis; Yachandra, Vittal K; Yano, Junko; Neese, Frank; Anxolabéhère-Mallart, Elodie

2010-07-01

Activation of a water molecule by the electrochemical oxidation of a Mn-aquo complex accompanied by the loss of protons is reported. The sequential (2 × 1 electron/1 proton) and direct (2 electron/2 proton) proton-coupled electrochemical oxidation of a non-porphyrinic six-coordinated Mn(II)OH 2 complex into a mononuclear Mn(O) complex is described. The intermediate Mn(III)OH 2 and Mn(III)OH complexes are electrochemically prepared and analysed. Complete deprotonation of the coordinated water molecule in the Mn(O) complex is confirmed by electrochemical data while the analysis of EXAFS data reveals a gradual shortening of an Mn-O bond upon oxidation from Mn(II)OH 2 to Mn(III)OH and Mn(O). Reactivity experiments, DFT calculations and XANES pre-edge features provide strong evidence that the bonding in Mn(O) is best characterized by a Mn(III)-oxyl description. Such oxyl species could play a crucial role in natural and artificial water splitting reactions. We provide here a synthetic example for such species, obtained by electrochemical activation of a water ligand.

Role of transmembrane segment 5 of the plant vacuolar H+-pyrophosphatase.

PubMed

Van, Ru C; Pan, Yih J; Hsu, Shen H; Huang, Yun T; Hsiao, Yi Y; Pan, Rong L

2005-08-15

Vacuolar H+-translocating inorganic pyrophosphatase (V-PPase; EC 3.6.1.1) is a homodimeric proton translocase consisting of a single type of polypeptide with a molecular mass of approximately 81 kDa. Topological analysis tentatively predicts that mung bean V-PPase contains 14 transmembrane domains. Alignment analysis of V-PPase demonstrated that the transmembrane domain 5 (TM5) of the enzyme is highly conserved in plants and located at the N-terminal side of the putative substrate-binding loop. The hydropathic analysis of V-PPase showed a relatively lower degree of hydrophobicity in the TM5 region as compared to other domains. Accordingly, it appears that TM5 is probably involved in the proton translocation of V-PPase. In this study, we used site-directed mutagenesis to examine the functional role of amino acid residues in TM5 of V-PPase. A series of mutants singly replaced by alanine residues along TM5 were constructed and over-expressed in Saccharomyces cerevisiae; they were then used to determine their enzymatic activities and proton translocations. Our results indicate that several mutants displayed minor variations in enzymatic properties, while others including those mutated at E225, a GYG motif (residues from 229 to 231), A238, and R242, showed a serious decline in enzymatic activity, proton translocation, and coupling efficiency of V-PPase. Moreover, the mutation at Y230 relieved several cation effects on the V-PPase. The GYG motif presumably plays a significant role in maintaining structure and function of V-PPase.

A comparative study of neutron activation analysis and proton-induced X-ray emission analysis for the determination of heavy metals in estuarine sediments

NASA Astrophysics Data System (ADS)

Randle, K.; Al-Jundi, J.; Mamas, C. J. V.; Sokhi, R. S.; Earwaker, L. G.

1993-06-01

Our work on heavy metals in the estuarine environment has involved the use of two multielement techniques: neutron activation analysis (NAA) and proton-induced X-ray emission (PIXE) analysis. As PIXE is essentially a surface analytical technique problems may arise due to sample inhomogeneity and surface roughness. In order to assess the contribution of these effects we have compared the results from PIXE analysis with those from a technique which analyzes a larger bulk sample rather than just the surface. An obvious method was NAA. A series of sediment samples containing particles of variable diameter were compared. Pellets containing a few mg of sediment were prepared from each sample and analyzed by the PIXE technique using both an absolute and a comparitive method. For INAA the rest of the sample was then irradiated with thermal neutrons and element concentrations determined from analyses of the subsequent gamma-ray spectrum. Results from the two methods are discussed.

Evolution of Proton and Alpha Particle Velocities through the Solar Cycle

NASA Astrophysics Data System (ADS)

Ďurovcová, T.; Šafránková, J.; Němeček, Z.; Richardson, J. D.

2017-12-01

Relative properties of solar wind protons and α particles are often used as indicators of a source region on the solar surface, and analysis of their evolution along the solar wind path tests our understanding of physics of multicomponent magnetized plasma. The paper deals with the comprehensive analysis of the difference between proton and α particle bulk velocities at 1 au with a special emphasis on interplanetary coronal mass ejections (ICMEs). A comparison of about 20 years of Wind observations at 1 au with Helios measurements closer to the Sun (0.3-0.7 au) generally confirms the present knowledge that (1) the differential speed between both species increases with the proton speed; (2) the differential speed is lower than the local Alfvén speed; (3) α particles are faster than protons near the Sun, and this difference decreases with the increasing distance. However, we found a much larger portion of observations with protons faster than α particles in Wind than in Helios data and attributed this effect to a preferential acceleration of the protons in the solar wind. A distinct population characterized by a very small differential velocity and nearly equal proton and α particle temperatures that is frequently observed around the maximum of solar activity was attributed to ICMEs. Since this population does not exhibit any evolution with increasing collisional age, we suggest that, by contrast to the solar wind from other sources, ICMEs are born in an equilibrium state and gradually lose this equilibrium due to interactions with the ambient solar wind.

Crystallographic Location and Mutational Analysis of Zn and Cd Inhibitory Sites and Role of Lipidic Carboxylates in Rescuing Proton Path Mutants in Cytochrome c Oxidase†

PubMed Central

Qin, Ling; Mills, Denise A.; Hiser, Carrie; Murphree, Anna; Garavito, R. Michael; Ferguson-Miller, Shelagh; Hosler, Jonathan

2008-01-01

Cytochrome c oxidase (CcO) transfers protons from the inner surface of the enzyme to the buried O2 reduction site through two different pathways, termed K and D, and from the outer surface via an undefined route. These proton paths can be inhibited by metals such as zinc or cadmium, but the sites of inhibition have not been established. Anomalous difference Fourier analyses of Rhodobacter sphaeroides CcO crystals, with cadmium added, reveal metal binding sites that include the proposed initial proton donor/acceptor of the K pathway, Glu-101 of subunit II. Mutant forms of CcO that lack Glu-101II (E101A and E101A/H96A) exhibit low activity and eliminate metal binding at this site. Significant activity is restored to E101A and E101A/H96A by adding the lipophilic carboxylic compounds, arachidonic acid and cholic acid, but not by their non-carboxylic analogues. These amphipathic acids likely provide their carboxylic groups as substitute proton donors/acceptors in the absence of Glu-101II, as previously observed for arachidonic acid in mutants that alter Asp-132I of the D pathway. The activity of E101A/H96A is still inhibited by zinc, but this remaining inhibition is nearly eliminated by removal of subunit III, which is known to alter the D pathway. The results identify the Glu-101/His-96 site of subunit II as the site of metal binding that inhibits the uptake of protons into the K pathway and indicate that subunit III contributes to zinc binding and/or inhibition of the D pathway. By removing subunit III from E101A/H96A, thereby eliminating zinc inhibition of the uptake of protons from the inner surface of CcO, we confirm that an external zinc binding site is involved in inhibiting the backflow of protons to the active site. PMID:17477548

Calcium regulation of oxidative phosphorylation in rat skeletal muscle mitochondria.

PubMed

Kavanagh, N I; Ainscow, E K; Brand, M D

2000-02-24

Activation of oxidative phosphorylation by physiological levels of calcium in mitochondria from rat skeletal muscle was analysed using top-down elasticity and regulation analysis. Oxidative phosphorylation was conceptually divided into three subsystems (substrate oxidation, proton leak and phosphorylation) connected by the membrane potential or the protonmotive force. Calcium directly activated the phosphorylation subsystem and (with sub-saturating 2-oxoglutarate) the substrate oxidation subsystem but had no effect on the proton leak kinetics. The response of mitochondria respiring on 2-oxoglutarate at two physiological concentrations of free calcium was quantified using control and regulation analysis. The partial integrated response coefficients showed that direct stimulation of substrate oxidation contributed 86% of the effect of calcium on state 3 oxygen consumption, and direct activation of the phosphorylation reactions caused 37% of the increase in phosphorylation flux. Calcium directly activated phosphorylation more strongly than substrate oxidation (78% compared to 45%) to achieve homeostasis of mitochondrial membrane potential during large increases in flux.

Roles of histidine residues in plant vacuolar H(+)-pyrophosphatase.

PubMed

Hsiao, Yi Y; Van, Ru C; Hung, Shu H; Lin, Hsin H; Pan, Rong L

2004-02-15

Vacuolar proton pumping pyrophosphatase (H(+)-PPase; EC 3.6.1.1) plays a pivotal role in electrogenic translocation of protons from cytosol to the vacuolar lumen at the expense of PP(i) hydrolysis. Alignment analysis on amino acid sequence demonstrates that vacuolar H(+)-PPase of mung bean contains six highly conserved histidine residues. Previous evidence indicated possible involvement of histidine residue(s) in enzymatic activity and H(+)-translocation of vacuolar H(+)-PPase as determined by using histidine specific modifier, diethylpyrocarbonate [J. Protein Chem. 21 (2002) 51]. In this study, we further attempted to identify the roles of histidine residues in mung bean vacuolar H(+)-PPase by site-directed mutagenesis. A line of mutants with histidine residues singly replaced by alanine was constructed, over-expressed in Saccharomyces cerevisiae, and then used to determine their enzymatic activities and proton translocations. Among the mutants scrutinized, only the mutation of H716 significantly decreased the enzymatic activity, the proton transport, and the coupling ratio of vacuolar H(+)-PPase. The enzymatic activity of H716A is relatively resistant to inhibition by diethylpyrocarbonate as compared to wild-type and other mutants, indicating that H716 is probably the target residue for the attack by this modifier. The mutation at H716 of V-PPase shifted the optimum pH value but not the T(1/2) (pretreatment temperature at which half enzymatic activity is observed) for PP(i) hydrolytic activity. Mutation of histidine residues obviously induced conformational changes of vacuolar H(+)-PPase as determined by immunoblotting analysis after limited trypsin digestion. Furthermore, mutation of these histidine residues modified the inhibitory effects of F(-) and Na(+), but not that of Ca(2+). Single substitution of H704, H716 and H758 by alanine partially released the effect of K(+) stimulation, indicating possible location of K(+) binding in the vicinity of domains surrounding these residues.

Effects of unsaturated fatty acids on the kinetics of voltage‐gated proton channels heterologously expressed in cultured cells

PubMed Central

Kawanabe, Akira

2016-01-01

Key points Arachidonic acid (AA) greatly enhances the activity of the voltage‐gated proton (Hv) channel, although its mechanism of action and physiological function remain unclear.In the present study, we analysed the effects of AA on proton currents through Hv channels heterologously expressed in HEK293T cells.The dramatic increase in proton current amplitude elicited by AA was accompanied by accelerated activation kinetics and a leftward shift in the voltage‐dependence of activation.Mutagenesis studies suggest the two aforementioned effects of AA reflect two distinct structural mechanisms.Application of phospholipase A2, which liberates AA from phospholipids in the membrane, also enhances Hv channel activity, supporting the idea that AA modulates Hv channel activity within physiological contexts. Abstract Unsaturated fatty acids are key components of the biological membranes of all cells, and precursors of mediators for cell signalling. Arachidonic acid (AA) is an unsaturated fatty acid known to modulate the activities of various ion channels, including the voltage‐gated proton (Hv) channel, which supports the rapid production of reactive oxygen species (ROS) in phagocytes through regulation of pH and membrane potential. However, the molecular mechanisms and physiological functions of the effects of AA on Hv channels remain unclear. In the present study, we report an electrophysiological analysis of the effects of AA on the mouse Hv channel (mHv1) heterologously expressed in HEK293T cells. Application of AA to excised inside‐out patch membranes rapidly induced a robust increase in the amplitude of the proton current through mHv1. The current increase was accompanied by accelerated activation kinetics and a small leftward shift of the current–voltage relationship. In monomeric channels lacking the coiled‐coil region of the channel protein, the shift in the current–voltage relationship was diminished but activation and deactivation remained accelerated. Studies with several AA derivatives showed that double bonds and hydrophilic head groups are essential for the effect of AA, although charge was not important. The application of phospholipase A2 (PLA2), which generates AA from cell membrane phospholipids, stimulated mHv1 activity to a similar extent as direct application of ∼20 μm AA, suggesting that endogenous AA may regulate Hv channel activity. PMID:26563684

Altering lipase activity and enantioselectivity in organic media using organo-soluble bases: Implication for rate-limiting proton transfer in acylation step.

PubMed

Chen, Chun-Chi; Chen, Teh-Liang; Tsai, Shau-Wei

2006-06-05

With the hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl esters via a partially purified papaya lipase (PCPL) in water-saturated isooctane as the model system, the enzyme activity, and enantioselectivty is altered by adding a variety of organo-soluble bases that act as either enzyme activators (i.e., TEA, MP, TOA, DPA, PY, and DMA) or enzyme inhibitors (i.e., PDP, DMAP, and PP). Triethylamine (TEA) is selected as the best enzyme activator as 2.24-fold increase of the initial rate for the (S)-ester is obtained when adding 120 mM of the base. By using an expanded Michaelis-Menten mechanism for the acylation step, the kinetic analysis indicates that the proton transfer for the breakdown of tetrahedral intermediates to acyl-enzyme intermediates is the rate-limiting step, or more sensitive than that for the formation of tetrahedral intermediates when the enzyme activators of different pKa are added. However, no correlation for the proton transfers in the acylation step is found when adding the bases acting as enzyme deactivators. Copyright 2006 Wiley Periodicals, Inc.

Induced activation study of LDEF

NASA Technical Reports Server (NTRS)

Harmon, B. A.; Fishman, G. J.; Parnell, T. A.; Laird, C. E.

1993-01-01

Analysis of the induced radioactivity of the Long Duration Exposure Facility (LDEF) is continuing with extraction of specific activities for various spacecraft materials. Data and results of activation measurements from eight facilities are being collected for interpretation at Eastern Kentucky University and NASA/Marshall Space Flight Center. The major activation mechanism in LDEF components is the proton flux in the South Atlantic Anomaly (SAA). This flux is highly anisotropic, and could be sampled by taking advantage of the gravity-gradient stabilization of the LDEF. The directionally-dependent activation due to these protons was clearly observed in the data from aluminum experiment tray clamps (reaction product Na-22), steel trunnions (reaction product Mn-54 and others) and is also indicated by the presence of a variety of nuclides in other materials. A secondary production mechanism, thermal neutron capture, was observed in cobalt, indium, and tantalum, which are known to have large capture cross sections. Experiments containing samples of these metals and significant amounts of thermalizing low atomic number (Z) material showed clear evidence of enhanced activation of Co-60, In-114m, and Ta-182. Other mechanisms which activate spacecraft material that are not as easily separable from SAA proton activation, such as galactic proton bombardment and secondary production by fast neutrons, are being investigated by comparison to radiation environmental calculations. Deviations from one-dimensional radiation models indicate that these mechanisms are more important at greater shielding depths. The current status of the induced radioactivity measurements as of mid-year 1992 are reviewed. Specific activities for a number of materials which show SAA effects and thermal neutron capture are presented. The results for consistency by combining data from the participating institutions is also examined.

Analysis of the irreversible process of proton transport in the purple membrane of Halobacterium halobium.

PubMed

Hong, T; Manqi, T

1980-04-01

The proton transport across biological membrane, accompanied by energy transformation, is closely related with many basic processes involved in the maintenance of life. Active researches are carried out in this field, but so far we have not known a complete calculation. This paper presents a model of an open and closed photon-controlled ion pore with a quantitative analysis of the irreversible process of the proton transport across the purple membrane. Upon absorbing photon by the purple membrane, the deprotonation of the Schiff base causes the ion pore to open, but it will close when it returns to bR570. A set of nonlinear differential equations describing this model is given. The stability of the equations is discussed. The results of the numerical calculation for steady state are found in good agreement with the experimental data of Bakker.

Modeling solubility, acid-base properties and activity coefficients of amoxicillin, ampicillin and (+)6-aminopenicillanic acid, in NaCl(aq) at different ionic strengths and temperatures.

PubMed

Crea, Francesco; Cucinotta, Daniela; De Stefano, Concetta; Milea, Demetrio; Sammartano, Silvio; Vianelli, Giuseppina

2012-11-20

The total solubility of three penicillin derivatives was determined, in pure water and NaCl aqueous solutions at different salt concentrations (from ∼0.15 to 1.0 mol L(-1) for ampicillin and amoxicillin, and from ∼0.05 to 2.0 mol L(-1) for (+)6-aminopenicillanic acid), using the shake-flask method for generating the saturated solutions, followed by potentiometric analysis. The knowledge of the pH of solubilization and of the protonation constants determined in the same experimental conditions, allowed us to calculate, by means of the mass balance equations, the solubility of the neutral species at different ionic strength values, to model its dependence on the salt concentration and to determine the corresponding values at infinite dilution. The salting parameter and the activity coefficients of the neutral species were calculated by the Setschenow equation. The protonation constants of ampicillin and amoxicillin, determined at different temperatures (from T=288.15 to 318.15K), from potentiometric and spectrophotometric measurements, were used to calculate, by means of the Van't Hoff equation, the temperature coefficients at different ionic strength values and the corresponding protonation entropies. The protonation enthalpies of the (+)6-aminopenicillanic acid were determined by isoperibol calorimetric titrations at T=298.15K and up to I=2.0 mol L(-1). The dependence of the protonation constants on ionic strength was modeled by means of the Debye-Hückel and SIT (Specific ion Interaction Theory) approaches, and the specific interaction parameters of the ionic species were determined. The hydrolysis of the β-lactam ring was studied by spectrophotometric and H NMR investigations as a function of pH, ionic strength and time. Potentiometric measurements carried out on the hydrolyzed (+)6-aminopenicillanic acid allowed us to highlight that the opened and the closed β-lactam forms of the (+)6-aminopenicillanic acid have quite different acid-base properties. An analysis of literature solubility, protonation constants, enthalpies and activity coefficients is reported too. Copyright © 2012 Elsevier B.V. All rights reserved.

Voltage-gated proton channel in a dinoflagellate

PubMed Central

Smith, Susan M. E.; Morgan, Deri; Musset, Boris; Cherny, Vladimir V.; Place, Allen R.; Hastings, J. Woodland; DeCoursey, Thomas E.

2011-01-01

Fogel and Hastings first hypothesized the existence of voltage-gated proton channels in 1972 in bioluminescent dinoflagellates, where they were thought to trigger the flash by activating luciferase. Proton channel genes were subsequently identified in human, mouse, and Ciona intestinalis, but their existence in dinoflagellates remained unconfirmed. We identified a candidate proton channel gene from a Karlodinium veneficum cDNA library based on homology with known proton channel genes. K. veneficum is a predatory, nonbioluminescent dinoflagellate that produces toxins responsible for fish kills worldwide. Patch clamp studies on the heterologously expressed gene confirm that it codes for a genuine voltage-gated proton channel, kHV1: it is proton-specific and activated by depolarization, its gH–V relationship shifts with changes in external or internal pH, and mutation of the selectivity filter (which we identify as Asp51) results in loss of proton-specific conduction. Indirect evidence suggests that kHV1 is monomeric, unlike other proton channels. Furthermore, kHV1 differs from all known proton channels in activating well negative to the Nernst potential for protons, EH. This unique voltage dependence makes the dinoflagellate proton channel ideally suited to mediate the proton influx postulated to trigger bioluminescence. In contrast to vertebrate proton channels, whose main function is acid extrusion, we propose that proton channels in dinoflagellates have fundamentally different functions of signaling and excitability. PMID:22006335

Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish

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

Mochimaru, Yuta; Azuma, Morio; Oshima, Natsuki

2015-02-20

Mammalian ovarian G-protein-coupled receptor 1 (OGR1) and GPR4 are identified as a proton-sensing G-protein-coupled receptor coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebra fish OGR1 and GPR4 homologs (zOGR1 and zGPR4) could sense protons and activate the multiple intracellular signaling pathways and, if so, whether the similar positions of histidine residue, which is critical for sensing protons in mammalian OGR and GPR4, also play a role to sense protons and activate the multiple signaling pathways in the zebra fish receptors. We found that extracellular acidic pH stimulated CRE-, SRE-, and NFAT-promoter activities in zOGR1more » overexpressed cells and stimulated CRE- and SRE- but not NFAT-promoter activities in zGPR4 overexpressed cells. The substitution of histidine residues at the 12th, 15th, 162th, and 264th positions from the N-terminal of zOGR1 with phenylalanine attenuated the proton-induced SRE-promoter activities. The mutation of the histidine residue at the 78th but not the 84th position from the N-terminal of zGPR4 to phenylalanine attenuated the proton-induced SRE-promoter activities. These results suggest that zOGR1 and zGPR4 are also proton-sensing G-protein-coupled receptors, and the receptor activation mechanisms may be similar to those of the mammalian receptors. - Highlights: • Zebra fish OGR1 and GPR4 homologs (zOGR1, zGPR4) are proton-sensing receptors. • The signaling pathways activated by zOGR1 and zGPR4 are different. • Histidine residues critical for sensing protons are conserved.« less

Long-term response of total ozone content at different latitudes of the Northern and Southern Hemispheres caused by solar activity during 1958-2006 (results of regression analysis)

NASA Astrophysics Data System (ADS)

Krivolutsky, Alexei A.; Nazarova, Margarita; Knyazeva, Galina

Solar activity influences on atmospheric photochemical system via its changebale electromag-netic flux with eleven-year period and also by energetic particles during solar proton event (SPE). Energetic particles penetrate mostly into polar regions and induce additional produc-tion of NOx and HOx chemical compounds, which can destroy ozone in photochemical catalytic cycles. Solar irradiance variations cause in-phase variability of ozone in accordance with photo-chemical theory. However, real ozone response caused by these two factors, which has different physical nature, is not so clear on long-term time scale. In order to understand the situation multiply linear regression statistical method was used. Three data series, which covered the period 1958-2006, have been used to realize such analysis: yearly averaged total ozone at dif-ferent latitudes (World Ozone Data Centre, Canada, WMO); yearly averaged proton fluxes with E¿ 10 MeV ( IMP, GOES, METEOR satellites); yearly averaged numbers of solar spots (Solar Data). Then, before the analysis, the data sets of ozone deviations from the mean values for whole period (1958-2006) at each latitudinal belt were prepared. The results of multiply regression analysis (two factors) revealed rather complicated time-dependent behavior of ozone response with clear negative peaks for the years of strong SPEs. The magnitudes of such peaks on annual mean basis are not greater than 10 DU. The unusual effect -positive response of ozone to solar proton activity near both poles-was discovered by statistical analysis. The pos-sible photochemical nature of found effect is discussed. This work was supported by Russian Science Foundation for Basic Research (grant 09-05-009949) and by the contract 1-6-08 under Russian Sub-Program "Research and Investigation of Antarctica".

SU-E-T-14: Modeling of 3D Positron Emission Activity Distributions Induced by Proton Irradiation: A Semi-Empirical Method.

PubMed

Lopatiuk-Tirpak, O; Su, Z; Hsi, W; Zeidan, O; Meeks, S

2012-06-01

to present and validate a method for modeling three-dimensional positron emission (PE) activity distributions induced by proton beam irradiation for PET/CT delivery verification studies in homogeneous media. the method relies on modeling the 3D proton flux distribution by combining the analytical expression for the depth reduction of proton flux with the empirically obtained lateral distribution. The latter is extracted from the corresponding dose distribution under the assumption that the projectile energy is nearly constant in the lateral plane. The same assumption allows calculating the 3D induced activity distributions from proton flux distributions by parameterizing the energy-dependent activation cross-sections in terms of depth via the energy-range relation. Results of this modeling approach were validated against experimental PET/CT data from three phantom deliveries: unmodulated (pristine) beam, spread-out Bragg peak (SOBP) delivery without a range compensator, and SOBP with a range compensator. BANG3-Pro2 polymer gel was used as a phantom material because of its elemental soft-tissue equivalence. the agreement between modeled and measured activity distributions was evaluated using 3D gamma index analysis method, which, despite being traditionally reserved for dose distribution comparisons, is sufficiently general to be applied to other quantities. The evaluation criteria were dictated by limitations of PET imaging and were chosen to correspond to count rate uncertainty (6% value difference) and spatial resolution (4 mm distance to agreement). With these criteria and the threshold of 6%, the fraction of evaluated voxels passing the gamma evaluation was 97.9% for the pristine beam, 98.9% for the SOBP without compensator, and 98.5% for SOBP with compensator. results of gamma evaluation indicate that the activity distributions produced by the model are consistent with experimental data within the uncertainties of PET imaging for clinical proton beams deliveries. This work was supported by the Bankhead-Coley Florida Biomedical Research Program under Grant No. 1BD10-34212. © 2012 American Association of Physicists in Medicine.

Range degradation and distal edge behavior of proton radiotherapy beams using 11C activation and Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Elmekawy, Ahmed Farouk

The distal edge of therapeutic proton radiation beams was investigated by different methods. Proton beams produced at the Hampton University Proton Therapy Institute (HUPTI) were used to irradiate a Polymethylmethacrylate (PMMA) phantom for three different ranges (13.5, 17.0 and 21.0 cm) to investigate the distal slope dependence of the Bragg peak. The activation of 11 C was studied by scanning the phantom less than 10 minutes post-irradiation with a Philips Big Bore Gemini(c) PET/CT. The DICOM images were imported into the Varian Eclipse(c) Treatment Planning System (TPS) for analysis and then analyzed by ImageJ(c) . The distal slope ranged from ?0.1671 +/- 0.0036 to -0.1986 +/- 0.0052 (pixel intensity/slice number) for ranges 13.5 to 21.0 cm respectively. A realistic description of the setup was modeled using the GATE 7.0 Monte Carlo simulation tool and compared to the experiment data. The results show the distal slope ranged from -0.1158+/-0.0133 to -0.0787+/-0.002 (Gy/mm). Additionally, low activity, 11C were simulated to study the 11C reconstructed half-life dependence versus the initial activity for six ranges chosen around the previous activation study. The results of the expected/nominal half-life vs. activity ranged from -5 x 10-4 +/- 2.8104 x 10-4 to 1.6 x 10-3 +/- 9.44 x 10-4 (%diff./Bq). The comparison between two experiments with proton beams on a PMMA phantom and multi-layer ion chamber, and two GATE simulations of a proton beam incident on a water phantom and 11C PET study show that: (i) the distal fall-off variation of the steepness of the slopes are found to be similar thus validating the sensitivity of the PET technique to the range degradation and (ii) the average of the super-ratios difference between all studies observed is primarily due to the difference in the dose deposited in the media.

Insight into proton transfer in phosphotungstic acid functionalized mesoporous silica-based proton exchange membrane fuel cells.

PubMed

Zhou, Yuhua; Yang, Jing; Su, Haibin; Zeng, Jie; Jiang, San Ping; Goddard, William A

2014-04-02

We have developed for fuel cells a novel proton exchange membrane (PEM) using inorganic phosphotungstic acid (HPW) as proton carrier and mesoporous silica as matrix (HPW-meso-silica) . The proton conductivity measured by electrochemical impedance spectroscopy is 0.11 S cm(-1) at 90 °C and 100% relative humidity (RH) with a low activation energy of ∼14 kJ mol(-1). In order to determine the energetics associated with proton migration within the HPW-meso-silica PEM and to determine the mechanism of proton hopping, we report density functional theory (DFT) calculations using the generalized gradient approximation (GGA). These DFT calculations revealed that the proton transfer process involves both intramolecular and intermolecular proton transfer pathways. When the adjacent HPWs are close (less than 17.0 Å apart), the calculated activation energy for intramolecular proton transfer within a HPW molecule is higher (29.1-18.8 kJ/mol) than the barrier for intermolecular proton transfer along the hydrogen bond. We find that the overall barrier for proton movement within the HPW-meso-silica membranes is determined by the intramolecular proton transfer pathway, which explains why the proton conductivity remains unchanged when the weight percentage of HPW on meso-silica is above 67 wt %. In contrast, the activation energy of proton transfer on a clean SiO2 (111) surface is computed to be as high as ∼40 kJ mol(-1), confirming the very low proton conductivity on clean silica surfaces observed experimentally.

Constitutive signaling by the phototaxis receptor sensory rhodopsin II from disruption of its protonated Schiff base–Asp-73 interhelical salt bridge

PubMed Central

Spudich, Elena N.; Zhang, Weisheng; Alam, Maqsudul; Spudich, John L.

1997-01-01

Sensory rhodopsin II (SRII) is a repellent phototaxis receptor in the archaeon Halobacterium salinarum, similar to visual pigments in its seven-helix structure and linkage of retinal to the protein by a protonated Schiff base in helix G. Asp-73 in helix C is shown by spectroscopic analysis to be a counterion to the protonated Schiff base in the unphotolyzed SRII and to be the proton acceptor from the Schiff base during photoconversion to the receptor signaling state. Coexpression of the genes encoding mutated SRII with Asn substituted for Asp-73 (D73N) and the SRII transducer HtrII in H. salinarum cells results in a 3-fold higher swimming reversal frequency accompanied by demethylation of HtrII in the dark, showing that D73N SRII produces repellent signals in its unphotostimulated state. Analogous constitutive signaling has been shown to be produced by the similar neutral residue substitution of the Schiff base counterion and proton acceptor Glu-113 in human rod rhodopsin. The interpretation for both seven-helix receptors is that light activation of the wild-type protein is caused primarily by photoisomerization-induced transfer of the Schiff base proton on helix G to its primary carboxylate counterion on helix C. Therefore receptor activation by helix C–G salt-bridge disruption in the photoactive site is a general mechanism in retinylidene proteins spanning the vast evolutionary distance between archaea and humans. PMID:9144172

Correlation of the antimicrobial activity of salicylaldehydes with broadening of the NMR signal of the hydroxyl proton. Possible involvement of proton exchange processes in the antimicrobial activity.

PubMed

Elo, Hannu; Kuure, Matti; Pelttari, Eila

2015-03-06

Certain substituted salicylaldehydes are potent antibacterial and antifungal agents and some of them merit consideration as potential chemotherapeutic agents against Candida infections, but their mechanism of action has remained obscure. We report here a distinct correlation between broadening of the NMR signal of the hydroxyl proton of salicylaldehydes and their activity against several types of bacteria and fungi. When proton NMR spectra of the compounds were determined using hexadeuterodimethylsulfoxide as solvent and the height of the OH proton signal was measured, using the signal of the aldehyde proton as an internal standard, it was discovered that a prerequisite of potent antimicrobial activity is that the proton signal is either unobservable or relatively very low, i.e. that it is extremely broadened. Thus, none of the congeners whose OH proton signal was high were potent antimicrobial agents. Some congeners that gave a very low OH signal were, however, essentially inactive against the microbes, indicating that although drastic broadening of the OH signal appears to be a prerequisite, also other (so far unknown) factors are needed for high antimicrobial activity. Because broadening of the hydroxyl proton signal is related to the speed of the proton exchange process(es) involving that proton, proton exchange may be involved in the mechanism of action of the compounds. Further studies are needed to analyze the relative importance of different factors (such as electronic effects, strength of the internal hydrogen bond, co-planarity of the ring and the formyl group) that determine the rates of those processes. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Antipsychotics, chlorpromazine and haloperidol inhibit voltage-gated proton currents in BV2 microglial cells.

PubMed

Shin, Hyewon; Song, Jin-Ho

2014-09-05

Microglial dysfunction and neuroinflammation are thought to contribute to the pathogenesis of schizophrenia. Some antipsychotic drugs have anti-inflammatory activity and can reduce the secretion of pro-inflammatory cytokines and reactive oxygen species from activated microglial cells. Voltage-gated proton channels on the microglial cells participate in the generation of reactive oxygen species and neuronal toxicity by supporting NADPH oxidase activity. In the present study, we examined the effects of two typical antipsychotics, chlorpromazine and haloperidol, on proton currents in microglial BV2 cells using the whole-cell patch clamp method. Chlorpromazine and haloperidol potently inhibited proton currents with IC50 values of 2.2 μM and 8.4 μM, respectively. Chlorpromazine and haloperidol are weak bases that can increase the intracellular pH, whereby they reduce the proton gradient and affect channel gating. Although the drugs caused a marginal positive shift of the activation voltage, they did not change the reversal potential. This suggested that proton current inhibition was not due to an alteration of the intracellular pH. Chlorpromazine and haloperidol are strong blockers of dopamine receptors. While dopamine itself did not affect proton currents, it also did not alter proton current inhibition by the two antipsychotics, indicating dopamine receptors are not likely to mediate the proton current inhibition. Given that proton channels are important for the production of reactive oxygen species and possibly pro-inflammatory cytokines, the anti-inflammatory and antipsychotic activities of chlorpromazine and haloperidol may be partly derived from their ability to inhibit microglial proton currents. Copyright © 2014 Elsevier B.V. All rights reserved.

Hyperthyroidism stimulates mitochondrial proton leak and ATP turnover in rat hepatocytes but does not change the overall kinetics of substrate oxidation reactions.

PubMed

Harper, M E; Brand, M D

1994-08-01

Thyroid hormones have well-known effects on oxidative phosphorylation, but there is little quantitative information on their important sites of action. We have used top-down elasticity analysis, an extension of metabolic control analysis, to identify the sites of action of thyroid hormones on oxidative phosphorylation in rat hepatocytes. We divided the oxidative phosphorylation system into three blocks of reactions: the substrate oxidation subsystem, the phosphorylating subsystem, and the mitochondrial proton leak subsystem and have identified those blocks of reactions whose kinetics are significantly changed by hyperthyroidism. Our results show significant effects on the kinetics of the proton leak and the phosphorylating subsystems. Quantitative analyses revealed that 43% of the increase in resting respiration rate in hyperthyroid hepatocytes compared with euthyroid hepatocytes was due to differences in the proton leak and 59% was due to differences in the activity of the phosphorylating subsystem. There were no significant effects on the substrate oxidation subsystem. Changes in nonmitochondrial oxygen consumption accounted for -2% of the change in respiration rate. Top-down control analysis revealed that the distribution of control over the rates of mitochondrial oxygen consumption, ATP synthesis and consumption, and proton leak and over mitochondrial membrane potential (delta psi m) was similar in hepatocytes from hyperthyroid and littermate-paired euthyroid controls. The results of this study include the first complete top-down elasticity and control analyses of oxidative phosphorylation in hepatocytes from hyperthyroid rats.

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.

Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala.

PubMed

Du, Jianyang; Reznikov, Leah R; Price, Margaret P; Zha, Xiang-ming; Lu, Yuan; Moninger, Thomas O; Wemmie, John A; Welsh, Michael J

2014-06-17

Stimulating presynaptic terminals can increase the proton concentration in synapses. Potential receptors for protons are acid-sensing ion channels (ASICs), Na(+)- and Ca(2+)-permeable channels that are activated by extracellular acidosis. Those observations suggest that protons might be a neurotransmitter. We found that presynaptic stimulation transiently reduced extracellular pH in the amygdala. The protons activated ASICs in lateral amygdala pyramidal neurons, generating excitatory postsynaptic currents. Moreover, both protons and ASICs were required for synaptic plasticity in lateral amygdala neurons. The results identify protons as a neurotransmitter, and they establish ASICs as the postsynaptic receptor. They also indicate that protons and ASICs are a neurotransmitter/receptor pair critical for amygdala-dependent learning and memory.

The development and clinical use of a beam ON-LINE PET system mounted on a rotating gantry port in proton therapy.

PubMed

Nishio, Teiji; Miyatake, Aya; Ogino, Takashi; Nakagawa, Keiichi; Saijo, Nagahiro; Esumi, Hiroyasu

2010-01-01

To verify the usefulness of our developed beam ON-LINE positron emission tomography (PET) system mounted on a rotating gantry port (BOLPs-RGp) for dose-volume delivery-guided proton therapy (DGPT). In the proton treatment room at our facility, a BOLPs-RGp was constructed so that a planar PET apparatus could be mounted with its field of view covering the iso-center of the beam irradiation system. Activity measurements were performed in 48 patients with tumors of the head and neck, liver, lungs, prostate, and brain. The position and intensity of the activity were measured using the BOLPs-RGp during the 200 s immediately after the proton irradiation. The daily measured activity images acquired by the BOLPs-RGp showed the proton irradiation volume in each patient. Changes in the proton-irradiated volume were indicated by differences between a reference activity image (taken at the first treatment) and the daily activity-images. In the case of head-and-neck treatment, the activity distribution changed in the areas where partial tumor reduction was observed. In the case of liver treatment, it was observed that the washout effect in necrotic tumor cells was slower than in non-necrotic tumor cells. The BOLPs-RGp was developed for the DGPT. The accuracy of proton treatment was evaluated by measuring changes of daily measured activity. Information about the positron-emitting nuclei generated during proton irradiation can be used as a basis for ensuring the high accuracy of irradiation in proton treatment.

Evaluation of the radiation hazard for ion-beam analysis with MeV external proton beams (X-IBA)

NASA Astrophysics Data System (ADS)

Hofsäss, Hans

2018-07-01

MeV ion beams which are extracted into air or He atmosphere are used in many labs for proton-induced X-ray emission (PIXE), proton induced gamma ray emission (PIGE) or Rutherford backscattering (RBS) to analyze samples which are difficult or impossible to handle in vacuum. When MeV proton beams are extracted into air through thin Kapton foils or nowadays thin silicon nitride membranes, the protons will interact with air, as well as elements present in the analyzed samples. Typically the range of MeV protons in air is several cm, in Helium atmosphere several 10 cm and in human skin around 100 μm. Besides the severe radiation hazard in case of a direct exposure of skin with protons, there are a manifold of nuclear reactions or inelastic proton scattering processes which may cause activation of air and target materials but also prompt radiation. The radiation hazard associated with the direct and scattered beam, nuclear reaction products and radionuclide production in air have been discussed in a publication by Doyle et al. in 1991 which was used as a reference in several later publications. I have reevaluated the radiation hazards for external proton beams with up to 4.5 MeV using proton reaction cross sections taken from the JANIS book of proton induced cross sections. The radionuclide production in air is about 3 orders of magnitude lower compared to values given in the 1991 publication. Radionuclide production as well as generation of prompt alpha, gamma and neutron radiation in target materials for elements up to molybdenum is also evaluated.

First Extraction of Transversity from a Global Analysis of Electron-Proton and Proton-Proton Data

NASA Astrophysics Data System (ADS)

Radici, Marco; Bacchetta, Alessandro

2018-05-01

We present the first extraction of the transversity distribution in the framework of collinear factorization based on the global analysis of pion-pair production in deep-inelastic scattering and in proton-proton collisions with a transversely polarized proton. The extraction relies on the knowledge of dihadron fragmentation functions, which are taken from the analysis of electron-positron annihilation data. For the first time, the transversity is extracted from a global analysis similar to what is usually done for the spin-averaged and helicity distributions. The knowledge of transversity is important for, among other things, detecting possible signals of new physics in high-precision low-energy experiments.

Studies of neutron and proton nuclear activation in low-Earth orbit

NASA Technical Reports Server (NTRS)

Laird, C. E.

1982-01-01

The expected induced radioactivity of experimental material in low Earth orbit was studied for characteristics of activating particles such as cosmic rays, high energy Earth albedo neutrons, trapped protons, and secondary protons and neutrons. The activation cross sections for the production of long lived radioisotopes and other existing nuclear data appropriate to the study of these reactions were compiled. Computer codes which are required to calculate the expected activation of orbited materials were developed. The decreased computer code used to predict the activation of trapped protons of materials placed in the expected orbits of LDEF and Spacelab II. Techniques for unfolding the fluxes of activating particles from the measured activation of orbited materials are examined.

Deletion mutation analysis on C-terminal domain of plant vacuolar H(+)-pyrophosphatase.

PubMed

Lin, Hsin Hung; Pan, Yih Jiuan; Hsu, Shen Hsing; Van, Ru Chuan; Hsiao, Yi Yuong; Chen, Jiun Hsien; Pan, Rong Long

2005-10-15

Vacuolar H(+)-translocating inorganic pyrophosphatase (V-PPase; EC 3.6.1.1) is a homodimeric proton-translocase; it contains a single type of polypeptide of approximately 81kDa. A line of evidence demonstrated that the carboxyl terminus of V-PPase is relatively conserved in various plant V-PPases and presumably locates in the vicinity of the catalytic site. In this study, we attempt to identify the roles of the C-terminus of V-PPase by generating a series of C-terminal deletion mutants over-expressed in Saccharomyces cerevisiae, and determining their enzymatic and proton translocating reactions. Our results showed that the deletion mutation at last 5 amino acids in the C-terminus (DeltaC5) induced a dramatic decline in enzymatic activity, proton translocation, and coupling efficiency of V-PPase; but the mutant lacking last 10 amino acids (DeltaC10) retained about 60-70% of the enzymatic activity of wild-type. Truncation of the C-terminus by more than 10 amino acids completely abolished the enzymatic activity and proton translocation of V-PPase. Furthermore, the DeltaC10 mutant displayed a shift in T(1/2) (pretreatment temperature at which half enzymatic activity is observed) but not the optimal pH for PP(i) hydrolytic activity. The deletion of the C-terminus substantially modified apparent K(+) binding constant, but exert no significant changes in the Na(+)-, F(-)-, and Ca(2+)-inhibition of the enzymatic activity of V-PPase. Taken together, we speculate that the C-terminus of V-PPase may play a crucial role in sustaining enzymatic activity and is likely involved in the K(+)-regulation of the enzyme in an indirect manner.

Synthesis and radical scavenging activity of 6-hydroxyl-4-methylcoumarin and its derivatives

NASA Astrophysics Data System (ADS)

Jumal, Juliana; Ayomide, Adetunji Fridaos

2018-06-01

Four compounds of coumarin derivatives namely 6-hydroxyl-4-methylcoumarin (I), 6-hydroxyl-4-methyl-5-(p-nitrophenyl azocoumarin) (II), 6-hydroxyl-4-methyl-5,7-(bis-p-nitrophenyl azocoumarin) (III) and 6-hydroxyl-4-methyl-5,7-(bis-p-chlorophenyl azocoumarin) (IV) were successfully synthesized. These compounds were prepared by reacting hydroquinone with ethylacetoacetate and selected anilines which are chloro and nitro aniline. All synthesized compounds were characterized by CHN micro-elemental analysis, 1H Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared (FTIR) spectroscopic methods. The infrared spectra of these compounds exhibited five important stretching vibrations: ʋ(-OH), ʋ(C=O), ʋ(C=C), ʋ(C-O) and ʋ(C-N) at 3441-3359 cm-1, 1604-1632 cm-1, 1581-1496 cm-1, 1331-1225 cm-1, 1251-1109 cm-1, respectively. 1H NMR spectra of these compounds show the presence of proton aromatic, proton methyl and proton pyrone ring with the chemical shift at δH 7.00-8.70 ppm, δH 2.20-2.50 ppm and δH 6.10-6.90 ppm, respectively. CHN analysis results of all compounds are in good agreement with the calculated values. All the synthesized compounds were evaluated for their antioxidant activity using DPPH method and ascorbic acid used as the standard. UV-Vis spectroscopic technique was used to investigate the absorbance of these compounds. Compound (II) shows high antioxidant activities compared to compound (I), (III) and (IV) which show moderate to low activities.

Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala

PubMed Central

Du, Jianyang; Reznikov, Leah R.; Price, Margaret P.; Zha, Xiang-ming; Lu, Yuan; Moninger, Thomas O.; Wemmie, John A.; Welsh, Michael J.

2014-01-01

Stimulating presynaptic terminals can increase the proton concentration in synapses. Potential receptors for protons are acid-sensing ion channels (ASICs), Na+- and Ca2+-permeable channels that are activated by extracellular acidosis. Those observations suggest that protons might be a neurotransmitter. We found that presynaptic stimulation transiently reduced extracellular pH in the amygdala. The protons activated ASICs in lateral amygdala pyramidal neurons, generating excitatory postsynaptic currents. Moreover, both protons and ASICs were required for synaptic plasticity in lateral amygdala neurons. The results identify protons as a neurotransmitter, and they establish ASICs as the postsynaptic receptor. They also indicate that protons and ASICs are a neurotransmitter/receptor pair critical for amygdala-dependent learning and memory. PMID:24889629

Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells.

PubMed

Song, Jin-Ho; Yeh, Jay Z

2012-05-10

Dextromethorphan, an antitussive drug, has a neuroprotective property as evidenced by its inhibition of microglial production of pro-inflammatory cytokines and reactive oxygen species. The microglial activation requires NADPH oxidase activity, which is sustained by voltage-gated proton channels in microglia as they dissipate an intracellular acid buildup. In the present study, we examined the effect of dextromethorphan on proton currents in microglial BV2 cells. Dextromethorphan reversibly inhibited proton currents with an IC(50) value of 51.7 μM at an intracellular/extracellular pH gradient of 5.5/7.3. Dextromethorphan did not change the reversal potential or the voltage dependence of the gating. Dextrorphan and 3-hydroxymorphinan, major metabolites of dextromethorphan, and dextromethorphan methiodide were ineffective in inhibiting proton currents. The results indicate that dextromethorphan inhibition of proton currents would suppress NADPH oxidase activity and, eventually, microglial activation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Mechanism of hypocoagulability in proton-irradiated ferrets

PubMed Central

Krigsfeld, Gabriel S.; Savage, Alexandria R.; Sanzari, Jenine K.; Wroe, Andrew J.; Gridley, Daila S.; Kennedy, Ann R.

2014-01-01

Purpose To determine the mechanism of proton radiation-induced coagulopathy. Material and methods Ferrets were exposed to either solar particle event (SPE)-like proton radiation at a predetermined dose rate of 0.5 Gray (Gy) per hour (h) for a total dose of 0 or 1 Gy. Blood was collected pre- and post-irradiation for a complete blood cell count or a soluble fibrin concentration analysis, to determine whether coagulation activation had occurred. Tissue was stained with an anti-fibrinogen antibody to confirm the presence of fibrin in blood vessels. Results SPE-like proton radiation exposure resulted in coagulation cascade activation, as determined by increased soluble fibrin concentration in blood from 0.7 – 2.4 at 3 h, and 9.9 soluble fibrin units (p < 0.05) at 24 h post-irradiation and fibrin clots in blood vessels of livers, lungs and kidneys from irradiated ferrets. In combination with this increase in fibrin clots, ferrets had increased prothrombin time and partial thromboplastin time values post-irradiation, which are representative of the extrinsic/intrinsic coagulation pathways. Platelet counts remained at pre-irradiation values over the course of 7 days, indicating that the observed effects were not platelet-related, but instead likely to be due to radiation-induced effects on secondary hemostasis. White blood cell (WBC) counts were reduced in a statistically significant manner from 24 h through the course of the seven-day experiment. Conclusions SPE-like proton radiation results in significant decreases in all WBC counts as well as activates secondary hemostasis; together, these data suggest severe risks to astronaut health from exposure to SPE radiation. PMID:23651328

Evidence for a zinc/proton antiporter in rat brain.

PubMed

Colvin, R A; Davis, N; Nipper, R W; Carter, P A

2000-05-01

The data presented in this paper are consistent with the existence of a plasma membrane zinc/proton antiport activity in rat brain. Experiments were performed using purified plasma membrane vesicles isolated from whole rat brain. Incubating vesicles in the presence of various concentrations of 65Zn2+ resulted in a rapid accumulation of 65Zn2+. Hill plot analysis demonstrated a lack of cooperativity in zinc activation of 65Zn2+ uptake. Zinc uptake was inhibited in the presence of 1 mM Ni2+, Cd2+, or CO2+. Calcium (1 mM) was less effective at inhibiting 65Zn2+ uptake and Mg2+ and Mn2+ had no effect. The initial rate of vesicular 65Zn2+ uptake was inhibited by increasing extravesicular H+ concentration. Vesicles preloaded with 65Zn2+ could be induced to release 65Zn2+ by increasing extravesicular H+ or addition of 1 mM nonradioactive Zn2+. Hill plot analysis showed a lack of cooperativity in H+ activation of 65Zn2+ release. Based on the Hill analyses, the stoichiometry of transport may include Zn2+/Zn2+ exchange and Zn2+/H+ antiport, the latter being potentially electrogenic. Zinc/proton antiport may be an important mode of zinc uptake into neurons and contribute to the reuptake of zinc to replenish presynaptic vesicle stores after stimulation.

Proton transfer and protein quake in photoreceptor activation

NASA Astrophysics Data System (ADS)

Xie, Aihua

2002-03-01

Proteins are able to perform an enormous variety of functions, while using only a limited number of underlying processes. One of these is proton transfer, found in a range of receptors and enzymes. It is conceivable that proton transfer is essential in biological energy transduction, but it is less evident how proton transfer is employed in receptor activation during biological signal transduction. An important question regarding receptor activation is how a localized event of detecting a stimulus at the active site drives global conformational changes involving protein surface for signal relay. We will present structural, kinetic and energetic studies on the activation mechanism of a prototype PAS domain photoreceptor, photoactive yellow protein (PYP). Our data reveal that the putative signaling state of PYP upon absorption of a blue photon is formed during a large-amplitude protein quake triggered by the formation of a new buried charge in a hydrophobic pocket at the active site of PYP via intramolecular proton transfer. This mechanism for protein quakes driven by proton transfer and electrostatic interactions may play roles during the functioning of other receptor proteins and non-receptor proteins that require large conformational changes.

Superoxide activates a GDP-sensitive proton conductance in skeletal muscle mitochondria from king penguin (Aptenodytes patagonicus).

PubMed

Talbot, Darren A; Hanuise, Nicolas; Rey, Benjamin; Rouanet, Jean-Louis; Duchamp, Claude; Brand, Martin D

2003-12-26

We present the partial nucleotide sequence of the avian uncoupling protein (avUCP) gene from king penguin (Aptenodytes patagonicus), showing that the protein is 88-92% identical to chicken (Gallus gallus), turkey (Meleagris gallopavo), and hummingbird (Eupetomena macroura). We show that superoxide activates the proton conductance of mitochondria isolated from king penguin skeletal muscle. GDP abolishes the superoxide-activated proton conductance, indicating that it is mediated via avUCP. In the absence of superoxide there is no GDP-sensitive component of the proton conductance from penguin muscle mitochondria demonstrating that avUCP plays no role in the basal proton leak.

In Vivo Noninvasive Analysis of Human Forearm Muscle Function and Fatigue: Applications to EVA Operations and Training Maneuvers

NASA Technical Reports Server (NTRS)

Fotedar, L. K.; Marshburn, T.; Quast, M. J.; Feeback, D. L.

1999-01-01

Forearm muscle fatigue is one of the major limiting factors affecting endurance during performance of deep-space extravehicular activity (EVA) by crew members. Magnetic resonance (MR) provides in vivo noninvasive analysis of tissue level metabolism and fluid exchange dynamics in exercised forearm muscles through the monitoring of proton magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (P-31-MRS) parameter variations. Using a space glove box and EVA simulation protocols, we conducted a preliminary MRS/MRI study in a small group of human test subjects during submaximal exercise and recovery and following exhaustive exercise. In assessing simulated EVA-related muscle fatigue and function, this pilot study revealed substantial changes in the MR image longitudinal relaxation times (T2) as an indicator of specific muscle activation and proton flux as well as changes in spectral phosphocreatine-to-phosphate (PCr/Pi) levels as a function of tissue bioenergetic potential.

Proton Transports in Pure Liquid Water Characterized by Melted Ice Lattice Model

NASA Astrophysics Data System (ADS)

Jie, Binbin; Sah, Chihtang

Basic water properties have not been understood for 200 years. Our Melted Ice Lattice model accounts for the 2 basic properties of pure water, the ion product (pH) and mobilities. It has HCP primitive unit cells, each with 4H2O, based on the 1933 Bernal-Fowler model, verified by 1935 Pauling residual entropy theory of 1928-1935 Giauque experimental low temperature specific heat measurements. Our 2 ion species are point-mass protons p + and p-, for mass and electricity transport. Three protonic thermal activation energies are obtained from pH and p + and p- mobilities vs T (0-100OC). Proton transport is analyzed in 3 proton-phonon collision steps: proton detrapping by protonic phonon absorption, proton scattering by oxygenic (water) phonons, and proton trapping with protonic phonon emission. Distinction between Potential and Kinetic Energy Bands of protons (Fermions) and phonons (Bosons) is noted. Experimental protonic activation energies are the phonon energies given by the spring-mass vibration frequencies of lattice, wn = (kn/mn)1/2 . n is the proton-mass unit of the synchronized vibrating particles in the primitive unit cells.

A conserved carboxylic acid group mediates light-dependent proton uptake and signaling by rhodopsin.

PubMed

Arnis, S; Fahmy, K; Hofmann, K P; Sakmar, T P

1994-09-30

A carboxylic acid residue is conserved at the cytoplasmic border of the third transmembrane segment among nearly all G protein-coupled receptors. In the visual receptor rhodopsin, replacement of the conserved Glu134 by a neutral glutamine results in enhanced transducin activation. Here we show that a key event in forming the active state of rhodopsin is proton uptake by Glu134 in the metarhodopsin II (MII) photoproduct. Site-directed mutants E134D and E134Q were studied by flash photolysis, where formation rates of their photoproducts and rates of pH change could be monitored simultaneously. Both mutants showed normal MII formation rates. However, E134D displayed a slowed rate of proton uptake and E134Q displayed a loss of light-induced uptake of two protons from the aqueous phase. Thus, Glu134 mediates light-dependent proton uptake by MII. We propose that receptor activation requires a light-induced conformational change that allows protonation of Glu134 and subsequent protonation of a second group. The strong conservation of Glu134 in G protein-coupled receptors implies a general requirement for a proton acceptor group at this position to allow light- or ligand-dependent receptor activation.

Proton Translocation in Cytochrome c Oxidase: Insights from Proton Exchange Kinetics and Vibrational Spectroscopy

PubMed Central

Ishigami, Izumi; Hikita, Masahide; Egawa, Tsuyoshi; Yeh, Syun-Ru; Rousseau, Denis L.

2014-01-01

Cytochrome c oxidase is the terminal enzyme in the electron transfer chain. It reduces oxygen to water and harnesses the released energy to translocate protons across the inner mitochondrial membrane. The mechanism by which the oxygen chemistry is coupled to proton translocation is not yet resolved owing to the difficulty of monitoring dynamic proton transfer events. Here we summarize several postulated mechanisms for proton translocation, which have been supported by a variety of vibrational spectroscopic studies. We recently proposed a proton translocation model involving proton accessibility to the regions near the propionate groups of the heme a and heme a3 redox centers of the enzyme based by hydrogen/deuterium (H/D) exchange Raman scattering studies (Egawa et al., PLOS ONE 2013). To advance our understanding of this model and to refine the proton accessibility to the hemes, the H/D exchange dependence of the heme propionate group vibrational modes on temperature and pH was measured. The H/D exchange detected at the propionate groups of heme a3 takes place within a few seconds under all conditions. In contrast, that detected at the heme a propionates occurs in the oxidized but not the reduced enzyme and the H/D exchange is pH-dependent with a pKa of ~8.0 (faster at high pH). Analysis of the thermodynamic parameters revealed that, as the pH is varied, entropy/enthalpy compensation held the free energy of activation in a narrow range. The redox dependence of the possible proton pathways to the heme groups is discussed. PMID:25268561

Undergraduate Research and Training in Ion-Beam Analysis of Environmental Materials

NASA Astrophysics Data System (ADS)

Vineyard, Michael F.; Chalise, Sajju; Clark, Morgan L.; LaBrake, Scott M.; McCalmont, Andrew M.; McGuire, Brendan C.; Mendez, Iseinie I.; Watson, Heather C.; Yoskowitz, Joshua T.

We have an active undergraduate research program at the Union College Ion-Beam Analysis Laboratory (UCIBAL) focused on the study of environmental materials. Accelerator-based ion-beam analysis (IBA) is a powerful tool for the study of environmental pollution because it can provide information on a broad range of elements with high sensitivity and low detection limits, is non-destructive, and requires little or no sample preparation. It also provides excellent training for the next generation of environmental scientists. Beams of protons and alpha particles with energies of a few MeV from the 1.1-MV tandem Pelletron accelerator (NEC Model 3SDH) in the UCIBAL are used to characterize environmental samples using IBA techniques such as proton-induced X-ray emission, Rutherford back-scattering, and proton-induced gamma-ray emission. Recent projects include the characterization of atmospheric aerosols in the Adirondack Mountains of upstate New York, the study of heavy metal pollutants in river sediment, measurements of Pb diffusion in sulfide minerals to help constrain the determination of the age of iron meteorites, and the search for heavy metals and toxins in artificial turf.

MS/MS Digital Readout: Analysis of Binary Information Encoded in the Monomer Sequences of Poly(triazole amide)s.

PubMed

Amalian, Jean-Arthur; Trinh, Thanh Tam; Lutz, Jean-François; Charles, Laurence

2016-04-05

Tandem mass spectrometry was evaluated as a reliable sequencing methodology to read codes encrypted in monodisperse sequence-coded oligo(triazole amide)s. The studied oligomers were composed of monomers containing a triazole ring, a short ethylene oxide segment, and an amide group as well as a short alkyl chain (propyl or isobutyl) which defined the 0/1 molecular binary code. Using electrospray ionization, oligo(triazole amide)s were best ionized as protonated molecules and were observed to adopt a single charge state, suggesting that adducted protons were located on every other monomer unit. Upon collisional activation, cleavages of the amide bond and of one ether bond were observed to proceed in each monomer, yielding two sets of complementary product ions. Distribution of protons over the precursor structure was found to remain unchanged upon activation, allowing charge state to be anticipated for product ions in the four series and hence facilitating their assignment for a straightforward characterization of any encoded oligo(triazole amide)s.

Impact of active geomagnetic conditions on stimulated radiation during ionospheric second electron gyroharmonic heating

NASA Astrophysics Data System (ADS)

Bordikar, M. R.; Scales, W. A.; Mahmoudian, A.; Kim, H.; Bernhardt, P. A.; Redmon, R.; Samimi, A. R.; Brizcinski, S.; McCarrick, M. J.

2014-01-01

Recently, narrowband emissions ordered near the H+ (proton) gyrofrequency (fcH) were reported in the stimulated electromagnetic emission (SEE) spectrum during active geomagnetic conditions. This work presents new observations and theoretical analysis of these recently discovered emissions. These emission lines are observed in the stimulated electromagnetic emission (SEE) spectrum when the transmitter is tuned near the second electron gyroharmonic frequency (2fce) during recent ionospheric modification experiments at the High Frequency Active Auroral Research (HAARP) facility near Gakona, Alaska. The spectral lines are typically shifted below and above the pump wave frequency by harmonics of a frequency roughly 10% less than fcH (≈ 800 Hz) with a narrow emission bandwidth less than the O+ gyrofrequency (≈ 50 Hz). However, new observations and analysis of emission lines ordered by a frequency approximately 10% greater than fcH are presented here for the first time as well. The interaction altitude for the heating for all the observations is in the range of 160 km up to 200 km. As described previously, proton precipitation due to active geomagnetic conditions is considered as the reason for the presence of H+ ions known to be a minor background constituent in this altitude region. DMSP satellite observations over HAARP during the heating experiments and ground-based magnetometer and riometer data validate active geomagnetic conditions. The theory of parametric decay instability in multi-ion component plasma including H+ ions as a minority species described in previous work is expanded in light of simultaneously observed preexisting SEE features to interpret the newly reported observations. Impact of active geomagnetic conditions on the SEE spectrum as a diagnostic tool for proton precipitation event characterization is discussed.

Involvement of histidine residues in the pH-dependent β-galactoside binding activity of human galectin-1.

PubMed

Hiramatsu, Hirotsugu; Takeuchi, Katsuyuki; Takeuchi, Hideo

2013-04-02

The pH dependence of the β-galactoside binding activity of human galectin-1 (hGal-1) was investigated by fluorescence spectroscopy using lactose as a ligand. The obtained binding constant Kb was 2.94 ± 0.10 mM(-1) at pH 7.5. The Kb value decreased at acidic pH with a midpoint of transition at pH 6.0 ± 0.1. To elucidate the molecular mechanism of the pH dependence, we investigated the structures of hGal-1 and its two His mutants (H44Q and H52Q) using fluorescence, circular dichroism, UV absorption, and UV resonance Raman spectroscopy. Analysis of the spectra has shown that the pKa values of His44 and His52 are 5.7 ± 0.2 and 6.3 ± 0.1, respectively. The protonation of His52 below pH 6.3 induces a small change in secondary structure and partly reduces the galactoside binding activity. On the other hand, the protonation of His44 below pH 5.7 exerts a cation-π interaction with Trp68 and largely diminishes the galactoside binding activity. With reference to the literature X-ray structures at pH 7.0 and 5.6, protonated His52 is proposed to move slightly away from the galactoside-binding region with a partial unfolding of the β-strand containing His52. On the other hand, protonated His44 becomes unable to form a hydrogen bond with galactoside and additionally induces a reorientation and/or displacement of Trp68 through cation-π interaction, leading to a loosening of the galactoside-binding pocket. These structural changes associated with His protonation are likely to be the origin of the pH dependence of the galactoside binding activity of hGal-1.

Identification and analysis of proton-translocating pyrophosphatases in the methanogenic archaeon Methanosarcina mazei

PubMed Central

Bäumer, Sebastian; Lentes, Sabine; Gottschalk, Gerhard; Deppenmeier, Uwe

2002-01-01

Analysis of genome sequence data from the methanogenic archaeon Methanosarcina mazei Gö1 revealed the existence of two open reading frames encoding proton-translocating pyrophosphatases (PPases). These open reading frames are linked by a 750-bp intergenic region containing TC-rich stretches and are transcribed in opposite directions. The corresponding polypeptides are referred to as Mvp1 and Mvp2 and consist of 671 and 676 amino acids, respectively. Both enzymes represent extremely hydrophobic, integral membrane proteins with 15 predicted transmembrane segments and an overall amino acid sequence similarity of 50.1%. Multiple sequence alignments revealed that Mvp1 is closely related to eukaryotic PPases, whereas Mvp2 shows highest homologies to bacterial PPases. Northern blot experiments with RNA from methanol-grown cells harvested in the mid-log growth phase indicated that only Mvp2 was produced under these conditions. Analysis of washed membranes showed that Mvp2 had a specific activity of 0.34 U mg (protein)–1. Proton translocation experiments with inverted membrane vesicles prepared from methanol-grown cells showed that hydrolysis of 1 mol of pyrophosphate was coupled to the translocation of about 1 mol of protons across the cytoplasmic membrane. Appropriate conditions for mvp1 expression could not be determined yet. The pyrophosphatases of M. mazei Gö1 represent the first examples of this enzyme class in methanogenic archaea and may be part of their energy-conserving system. Abbreviations: DCCD, N,N′-dicyclohexylcarbodiimide; PPase, inorganic pyrophosphatase; PPi, inorganic pyrophosphate; Δp, proton motive force. PMID:15803653

Hydrogen molecule defect in proton-conductive SrTiO3 Perovskite

NASA Astrophysics Data System (ADS)

Onishi, Taku

2017-11-01

In proton-conductive SrTiO3 perovskite, no hydrogen molecule defect ideally exists. However, the unforeseen chemical reaction is often observed after the use of fuel cell. From the viewpoint of battery safety, we have investigated the effect of hydrogen molecule defect by molecular orbital analysis. When counter cation vacancy exists, the activation energy for hydrogen molecule migration was 1.39 - 1.50 eV, which is much smaller than the dissociation energy of hydrogen molecule. It implies that hydrogen molecule may migrate without its dissociation.

Surface Protonics Promotes Catalysis

PubMed Central

Manabe, R.; Okada, S.; Inagaki, R.; Oshima, K.; Ogo, S.; Sekine, Y.

2016-01-01

Catalytic steam reforming of methane for hydrogen production proceeds even at 473 K over 1 wt% Pd/CeO2 catalyst in an electric field, thanks to the surface protonics. Kinetic analyses demonstrated the synergetic effect between catalytic reaction and electric field, revealing strengthened water pressure dependence of the reaction rate when applying an electric field, with one-third the apparent activation energy at the lower reaction temperature range. Operando–IR measurements revealed that proton conduction via adsorbed water on the catalyst surface occurred during electric field application. Methane was activated by proton collision at the Pd–CeO2 interface, based on the inverse kinetic isotope effect. Proton conduction on the catalyst surface plays an important role in methane activation at low temperature. This report is the first describing promotion of the catalytic reaction by surface protonics. PMID:27905505

Preparations of an inorganic-framework proton exchange nanochannel membrane

NASA Astrophysics Data System (ADS)

Yan, X. H.; Jiang, H. R.; Zhao, G.; Zeng, L.; Zhao, T. S.

2016-09-01

In this work, a proton exchange membrane composed of straight and aligned proton conducting nanochannels is developed. Preparation of the membrane involves the surface sol-gel method assisted with a through-hole anodic aluminum oxide (AAO) template to form the framework of the PEM nanochannels. A monomolecular layer (SO3Hsbnd (CH2)3sbnd Sisbnd (OCH3)3) is subsequently added onto the inner surfaces of the nanochannels to shape a proton-conducting pathway. Straight nanochannels exhibit long range order morphology, contributing to a substantial improvement in the proton mobility and subsequently proton conductivity. In addition, the nanochannel size can be altered by changing the surface sol-gel condition, allowing control of the active species/charge carrier selectivity via pore size exclusion. The proton conductivity of the nanochannel membrane is reported as high as 11.3 mS cm-1 at 70 °C with a low activation energy of 0.21 eV (20.4 kJ mol-1). First-principle calculations reveal that the activation energy for proton transfer is impressively low (0.06 eV and 0.07 eV) with the assistance of water molecules.

Identification and analysis of proton-translocating pyrophosphatases in the methanogenic archaeon Methansarcina mazei.

PubMed

Bäumer, Sebastian; Lentes, Sabine; Gottschalk, Gerhard; Deppenmeier, Uwe

2002-03-01

Analysis of genome sequence data from the methanogenic archaeon Methanosarcina mazei Gö1 revealed the existence of two open reading frames encoding proton-translocating pyrophosphatases (PPases). These open reading frames are linked by a 750-bp intergenic region containing TC-rich stretches and are transcribed in opposite directions. The corresponding polypeptides are referred to as Mvp1 and Mvp2 and consist of 671 and 676 amino acids, respectively. Both enzymes represent extremely hydrophobic, integral membrane proteins with 15 predicted transmembrane segments and an overall amino acid sequence similarity of 50.1%. Multiple sequence alignments revealed that Mvp1 is closely related to eukaryotic PPases, whereas Mvp2 shows highest homologies to bacterial PPases. Northern blot experiments with RNA from methanol-grown cells harvested in the mid-log growth phase indicated that only Mvp2 was produced under these conditions. Analysis of washed membranes showed that Mvp2 had a specific activity of 0.34 U mg (protein)(-1). Proton translocation experiments with inverted membrane vesicles prepared from methanol-grown cells showed that hydrolysis of 1 mol of pyrophosphate was coupled to the translocation of about 1 mol of protons across the cytoplasmic membrane. Appropriate conditions for mvp1 expression could not be determined yet. The pyrophosphatases of M. mazei Gö1 represent the first examples of this enzyme class in methanogenic archaea and may be part of their energy-conserving system.

Active Proton Interrogation for Homeland Security

NASA Astrophysics Data System (ADS)

Greene, Steven; Morris, Christopher; Canavan, Gregory; Chung, Kiwhan; Elson, Jay; Hogan, Gary; Makela, Mark; Mariam, Fesseha; Murray, Matthew; Saunders, Alexander; Spaulding, Randy; Wang, Zhehui; Waters, Laurie; Wysocki, Frederick

2010-02-01

Energetic proton beams may provide an attractive technology for active interrogation of nuclear threats because: they have large fission cross sections, long mean free paths and high penetration, and proton beams can be manipulated with magnetic optics. We have measured time-dependent cross sections for delayed neutrons and gamma rays using 800 MeV protons from the Los Alamos Neutron Science Center and 4 GeV protons from the Brookhaven Alternating Gradient Synchrotron for a set of bare and shielded targets. The results show significant signals from both unshielded and shielded nuclear materials. Results will be presented. )

Comparison of short-lived medical isotopes activation by laser thin target induced protons and conventional cyclotron proton beams

NASA Astrophysics Data System (ADS)

Murray, Joseph; Dudnikova, Galina; Liu, Tung-Chang; Papadopoulos, Dennis; Sagdeev, Roald; Su, J. J.; UMD MicroPET Team

2014-10-01

Production diagnostic or therapeutic nuclear medicines are either by nuclear reactors or by ion accelerators. In general, diagnostic nuclear radioisotopes have a very short half-life varying from tens of minutes for PET tracers and few hours for SPECT tracers. Thus supplies of PET and SPECT radiotracers are limited by regional production facilities. For example 18F-fluorodeoxyglucose (FDG) is the most desired tracer for positron emission tomography because its 110 minutes half-life is sufficient long for transport from production facilities to nearby users. From nuclear activation to completing image taking must be done within 4 hours. Decentralized production of diagnostic radioisotopes will be idea to make high specific activity radiotracers available to researches and clinicians. 11 C, 13 N, 15 O and 18 F can be produced in the energy range from 10-20 MeV by protons. Protons of energies up to tens of MeV generated by intense laser interacting with hydrogen containing targets have been demonstrated by many groups in the past decade. We use 2D PIC code for proton acceleration, Geant4 Monte Carlo code for nuclei activation to compare the yields and specific activities of short-lived isotopes produced by cyclotron proton beams and laser driven protons.

Alternative initial proton acceptors for the D pathway of Rhodobacter sphaeroides cytochrome c oxidase

PubMed Central

Varanasi, Lakshman; Hosler, Jonathan

2011-01-01

In order to characterize protein structures that control proton uptake, forms of cytochrome c oxidase (CcO) containing a carboxyl or a thiol group in line with the initial, internal waters of the D pathway for proton transfer have been assayed in the presence and absence of subunit III. Subunit III provides approximately half of the protein surrounding the entry region of the D pathway. The mutant N139D-D132N contains a carboxyl group 6Å within the D pathway and lacks the normal, surface-exposed proton acceptor, Asp-132. With subunit III, the steady-state activity of this mutant is slow but once subunit III is removed its activity is the same as wild-type CcO lacking subunit III (∼1800 H+ s-1). Thus, a carboxyl group ∼25% within the pathway enhances proton uptake even though the carboxyl has no direct contact with bulk solvent. Protons from solvent apparently move to internal Asp-139 through a short file of waters, normally blocked by subunit III. Cysteine-139 also supports rapid steady-state proton uptake, demonstrating that an anion other than a carboxyl can attract and transfer protons into the D pathway. When both Asp-132 and Asp/Cys-139 are present, the removal of subunit III increases CcO activity to rates greater than that of normal CcO due to simultaneous proton uptake by two initial acceptors. The results show how the environment of the initial proton acceptor for the D pathway in these CcO forms dictates the pH range of CcO activity, with implications for the function of Asp-132, the normal proton acceptor. PMID:21344856

National Cancer Database Analysis of Proton Versus Photon Radiation Therapy in Non-Small Cell Lung Cancer

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

Higgins, Kristin A., E-mail: kristin.higgins@emory.edu; Winship Cancer Institute, Emory University, Atlanta, Georgia; O'Connell, Kelli

Purpose: To analyze outcomes and predictors associated with proton radiation therapy for non-small cell lung cancer (NSCLC) in the National Cancer Database. Methods and Materials: The National Cancer Database was queried to capture patients with stage I-IV NSCLC treated with thoracic radiation from 2004 to 2012. A logistic regression model was used to determine the predictors for utilization of proton radiation therapy. The univariate and multivariable association with overall survival were assessed by Cox proportional hazards models along with log–rank tests. A propensity score matching method was implemented to balance baseline covariates and eliminate selection bias. Results: A total of 243,822more » patients (photon radiation therapy: 243,474; proton radiation therapy: 348) were included in the analysis. Patients in a ZIP code with a median income of <$46,000 per year were less likely to receive proton treatment, with the income cohort of $30,000 to $35,999 least likely to receive proton therapy (odds ratio 0.63 [95% confidence interval (CI) 0.44-0.90]; P=.011). On multivariate analysis of all patients, non-proton therapy was associated with significantly worse survival compared with proton therapy (hazard ratio 1.21 [95% CI 1.06-1.39]; P<.01). On propensity matched analysis, proton radiation therapy (n=309) was associated with better 5-year overall survival compared with non-proton radiation therapy (n=1549), 22% versus 16% (P=.025). For stage II and III patients, non-proton radiation therapy was associated with worse survival compared with proton radiation therapy (hazard ratio 1.35 [95% CI 1.10-1.64], P<.01). Conclusions: Thoracic radiation with protons is associated with better survival in this retrospective analysis; further validation in the randomized setting is needed to account for any imbalances in patient characteristics, including positron emission tomography–computed tomography staging.« less

Proton Transfer in the Catalytic Cycle of [NiFe] Hydrogenases: Insight from Vibrational Spectroscopy

PubMed Central

2017-01-01

Catalysis of H2 production and oxidation reactions is critical in renewable energy systems based around H2 as a clean fuel, but the present reliance on platinum-based catalysts is not sustainable. In nature, H2 is oxidized at minimal overpotential and high turnover frequencies at [NiFe] catalytic sites in hydrogenase enzymes. Although an outline mechanism has been established for the [NiFe] hydrogenases involving heterolytic cleavage of H2 followed by a first and then second transfer of a proton and electron away from the active site, details remain vague concerning how the proton transfers are facilitated by the protein environment close to the active site. Furthermore, although [NiFe] hydrogenases from different organisms or cellular environments share a common active site, they exhibit a broad range of catalytic characteristics indicating the importance of subtle changes in the surrounding protein in controlling their behavior. Here we review recent time-resolved infrared (IR) spectroscopic studies and IR spectroelectrochemical studies carried out in situ during electrocatalytic turnover. Additionally, we re-evaluate the significant body of IR spectroscopic data on hydrogenase active site states determined through more conventional solution studies, in order to highlight mechanistic steps that seem to apply generally across the [NiFe] hydrogenases, as well as steps which so far seem limited to specific groups of these enzymes. This analysis is intended to help focus attention on the key open questions where further work is needed to assess important aspects of proton and electron transfer in the mechanism of [NiFe] hydrogenases. PMID:28413691

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.

Transepithelial transport of flavanone in intestinal Caco-2 cell monolayers

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

Kobayashi, Shoko; Konishi, Yutaka

2008-03-28

Our recent study [S. Kobayashi, S. Tanabe, M. Sugiyama, Y. Konishi, Transepithelial transport of hesperetin and hesperidin in intestinal Caco-2 cell monolayers, Biochim. Biophys. Acta, 1778 (2008) 33-41] shows that the mechanism of absorption of hesperetin involves both proton-coupled active transport and transcellular passive diffusion. Here, as well as analyzing the cell permeability of hesperetin, we also study the transport of other flavanones, naringenin and eriodictyol, using Caco-2 cell monolayers. Similar to hesperetin mentioned, naringenin and eriodictyol showed proton-coupled polarized transport in apical-to-basolateral direction in non-saturable manner, constant permeation in the apical-to-basolateral direction (J{sub ap{yields}}{sub bl}) irrespective of the transepithelialmore » electrical resistance (TER), and preferable distribution into the basolateral side after apical loading in the presence of a proton gradient. Furthermore, the proton-coupled J{sub ap{yields}}{sub bl} of hesperetin, naringenin and eriodictyol, were inhibited by substrates of the monocarboxylic acid transporter (MCT), such as benzoic acid, but not by ferulic acid. In contrast, both benzoic and ferulic acids have no stimulatory effect on J{sub ap{yields}}{sub bl} of each flavanone by trans-stimulation analysis. These results indicates that proton-driven active transport is commonly participated in the absorption of flavanone in general, and that its transport is presumed to be unique other than MCT-mediated transport for absorption of phenolic acids (PAs), sodium-dependent MCT (SMCT) nor anion exchanger-mediated transport.« less

The Effects of High Steady State Auxin Levels on Root Cell Elongation in Brachypodium[OPEN

PubMed Central

Pacheco-Villalobos, David; Tamaki, Takayuki; Gujas, Bojan; Jaspert, Nina; Oecking, Claudia; Bulone, Vincent; Hardtke, Christian S.

2016-01-01

The long-standing Acid Growth Theory of plant cell elongation posits that auxin promotes cell elongation by stimulating cell wall acidification and thus expansin action. To date, the paucity of pertinent genetic materials has precluded thorough analysis of the importance of this concept in roots. The recent isolation of mutants of the model grass species Brachypodium distachyon with dramatically enhanced root cell elongation due to increased cellular auxin levels has allowed us to address this question. We found that the primary transcriptomic effect associated with elevated steady state auxin concentration in elongating root cells is upregulation of cell wall remodeling factors, notably expansins, while plant hormone signaling pathways maintain remarkable homeostasis. These changes are specifically accompanied by reduced cell wall arabinogalactan complexity but not by increased proton excretion. On the contrary, we observed a tendency for decreased rather than increased proton extrusion from root elongation zones with higher cellular auxin levels. Moreover, similar to Brachypodium, root cell elongation is, in general, robustly buffered against external pH fluctuation in Arabidopsis thaliana. However, forced acidification through artificial proton pump activation inhibits root cell elongation. Thus, the interplay between auxin, proton pump activation, and expansin action may be more flexible in roots than in shoots. PMID:27169463

Integration of a 'proton antenna' facilitates transport activity of the monocarboxylate transporter MCT4.

PubMed

Noor, Sina Ibne; Pouyssegur, Jacques; Deitmer, Joachim W; Becker, Holger M

2017-01-01

Monocarboxylate transporters (MCTs) mediate the proton-coupled transport of high-energy metabolites like lactate and pyruvate and are expressed in nearly every mammalian tissue. We have shown previously that transport activity of MCT4 is enhanced by carbonic anhydrase II (CAII), which has been suggested to function as a 'proton antenna' for the transporter. In the present study, we tested whether creation of an endogenous proton antenna by introduction of a cluster of histidine residues into the C-terminal tail of MCT4 (MCT4-6xHis) could facilitate MCT4 transport activity when heterologously expressed in Xenopus oocytes. Our results show that integration of six histidines into the C-terminal tail does indeed increase transport activity of MCT4 to the same extent as did coexpression of MCT4-WT with CAII. Transport activity of MCT4-6xHis could be further enhanced by coexpression with extracellular CAIV, but not with intracellular CAII. Injection of an antibody against the histidine cluster into MCT4-expressing oocytes decreased transport activity of MCT4-6xHis, while leaving activity of MCT4-WT unaltered. Taken together, these findings suggest that transport activity of the proton-coupled monocarboxylate transporter MCT4 can be facilitated by integration of an endogenous proton antenna into the transporter's C-terminal tail. © 2016 Federation of European Biochemical Societies.

Comparative analysis of cation/proton antiporter superfamily in plants.

PubMed

Ye, Chu-Yu; Yang, Xiaohan; Xia, Xinli; Yin, Weilun

2013-06-01

The cation/proton antiporter superfamily is associated with the transport of monovalent cations across membranes. This superfamily was annotated in the Arabidopsis genome and some members were functionally characterized. In the present study, a systematic analysis of the cation/proton antiporter genes in diverse plant species was reported. We identified 240 cation/proton antiporters in alga, moss, and angiosperm. A phylogenetic tree was constructed showing these 240 members are separated into three families, i.e., Na(+)/H(+) exchangers, K(+) efflux antiporters, and cation/H(+) exchangers. Our analysis revealed that tandem and/or segmental duplications contribute to the expansion of cation/H(+) exchangers in the examined angiosperm species. Sliding window analysis of the nonsynonymous/synonymous substitution ratios showed some differences in the evolutionary fate of cation/proton antiporter paralogs. Furthermore, we identified over-represented motifs among these 240 proteins and found most motifs are family specific, demonstrating diverse evolution of the cation/proton antiporters among three families. In addition, we investigated the co-expressed genes of the cation/proton antiporters in Arabidopsis thaliana. The results showed some biological processes are enriched in the co-expressed genes, suggesting the cation/proton antiporters may be involved in these biological processes. Taken together, this study furthers our knowledge on cation/proton antiporters in plants. Copyright © 2013 Elsevier B.V. All rights reserved.

Timepix Device Efficiency for Pattern Recognition of Tracks Generated by Ionizing Radiation

NASA Astrophysics Data System (ADS)

Leroy, Claude; Asbah, Nedaa; Gagnon, Louis-Guilaume; Larochelle, Jean-Simon; Pospisil, Stanislav; Soueid, Paul

2014-06-01

A hybrid silicon pixelated TIMEPIX detector (256 × 256 pixels with 55 μm pitch) operated in Time Over Threshold (TOT) mode was exposed to radioactive sources (241Am, 106Ru, 137Cs), protons and alpha-particles after Rutherford Backscattering on a thin gold foil of protons and alpha-particles beams delivered by the Tandem Accelerator of Montreal University. Measurements were also performed with different mixed radiation fields of heavy charged particles (protons and alpha-particles), photons and electrons produced by simultaneous exposure of TIMEPIX to the radioactive sources and to protons beams on top of the radioactive sources. All measurements were performed in vacuum. The TOT mode of operation has allowed the direct measurement of the energy deposited in each pixel. The efficiency of track recognition with this device was tested by comparing the experimental activities (determined from number of tracks measurements) of the radioactive sources with their expected activities. The efficiency of track recognition of incident protons and alpha-particles of different energies as a function of the incidence angle was measured. The operation of TIMEPIX in TOT mode has allowed a 3D mapping of the charge sharing effect in the whole volume of the silicon sensor. The effect of the bias voltage on charge sharing was investigated as the level of charge sharing is related to the local profile of the electric field in the sensor. The results of the present measurements demonstrate the TIMEPIX capability of differentiating between different types of particles species from mixed radiation fields and measuring their energy deposition. Single track analysis gives a good precision (significantly better than the 55 μm size of one detector pixel) on the coordinates of the impact point of protons interacting in the TIMEPIX silicon layer.

Inhibitory effects of antihistamines, diphenhydramine and chlorpheniramine, on proton currents in BV2 microglial cells.

PubMed

Kim, Jiwon; Song, Jin-Ho

2017-03-05

Microglial NADPH oxidase is a major source of toxic reactive oxygen species produced during chronic neuroinflammation. Voltage-gated proton channel (H V 1) functions to maintain the intense activity of NADPH oxidase, and channel inhibition alleviates the pathology of neurodegenerative diseases such as ischemic stroke and multiple sclerosis associated with oxidative neuroinflammation. Antagonists of histamine H 1 receptors have beneficial effects against microglia-mediated oxidative stress and neurotoxicity. We examined the effects of the H 1 antihistamines, diphenhydramine and chlorpheniramine, on proton currents in BV2 microglial cells recorded using the whole-cell patch clamp technique. Diphenhydramine and chlorpheniramine reduced the proton currents with almost the same potency, yielding IC 50 values of 42 and 43μM, respectively. Histamine did not affect proton currents, excluding the involvement of histamine receptors in their action. Neither drug shifted the voltage-dependence of activation or the reversal potential of the proton currents, even though diphenhydramine slowed the activation and deactivation kinetics. The inhibitory effects of the two antihistamines on proton currents could be utilized to develop therapeutic agents for neurodegenerative diseases and other diseases associated with H V 1 proton channel abnormalities. Copyright © 2017 Elsevier B.V. All rights reserved.

Citrate Accumulation-Related Gene Expression and/or Enzyme Activity Analysis Combined With Metabolomics Provide a Novel Insight for an Orange Mutant

PubMed Central

Guo, Ling-Xia; Shi, Cai-Yun; Liu, Xiao; Ning, Dong-Yuan; Jing, Long-Fei; Yang, Huan; Liu, Yong-Zhong

2016-01-01

‘Hong Anliu’ (HAL, Citrus sinensis cv. Hong Anliu) is a bud mutant of ‘Anliu’ (AL), characterized by a comprehensive metabolite alteration, such as lower accumulation of citrate, high accumulation of lycopene and soluble sugars in fruit juice sacs. Due to carboxylic acid metabolism connects other metabolite biosynthesis and/or catabolism networks, we therefore focused analyzing citrate accumulation-related gene expression profiles and/or enzyme activities, along with metabolic fingerprinting between ‘HAL’ and ‘AL’. Compared with ‘AL’, the transcript levels of citrate biosynthesis- and utilization-related genes and/or the activities of their respective enzymes such as citrate synthase, cytosol aconitase and ATP-citrate lyase were significantly higher in ‘HAL’. Nevertheless, the mitochondrial aconitase activity, the gene transcript levels of proton pumps, including vacuolar H+-ATPase, vacuolar H+-PPase, and the juice sac-predominant p-type proton pump gene (CsPH8) were significantly lower in ‘HAL’. These results implied that ‘HAL’ has higher abilities for citrate biosynthesis and utilization, but lower ability for the citrate uptake into vacuole compared with ‘AL’. Combined with the metabolites-analyzing results, a model was then established and suggested that the reduction in proton pump activity is the key factor for the low citrate accumulation and the comprehensive metabolite alterations as well in ‘HAL’. PMID:27385485

Characteristics of proton beams and secondary neutrons arising from two different beam nozzles

NASA Astrophysics Data System (ADS)

Choi, Yeon-Gyeong; Kim, Yu-Seok

2015-10-01

A tandem or a Van de Graaff accelerator with an energy of 3 MeV is typically used for Proton Induced X-ray Emission (PIXE) analysis. In this study, the beam line design used in the PIXE analysis, instead of the typical low-energy accelerator, was used to increase the production of isotopes from a 13-MeV cyclotron. For the PIXE analysis, the proton beam should be focused at the target through a nozzle after degrading the proton beams energy from 13 MeV to 3 MeV by using an energy degrader. Previous studies have been conducted to determine the most appropriate material for and the thickness of the energy degrader. From the energy distribution of the degraded proton beam and the neutron occurrence rate at the degrader, an aluminum nozzle of X thickness was determined to be the most appropriate nozzle construction. Neutrons are created by the collision of 3-MeV protons in the nozzle after passage through the energy degrader. In addition, a proton beam of sufficient intensity is required for a non-destructive PIXE analysis. Therefore, if nozzle design is to be optimized, the number of neutrons that arise from the collision of protons inside the nozzle, as well as the track direction of the generated secondary neutrons, must be considered, with the primary aim of ensuring that a sufficient number of protons pass through the nozzle as a direct beam. A number of laboratories are currently conducting research related to the design of nozzles used in accelerator fields, mostly medical fields. This paper presents a comparative analysis of two typical nozzle shapes in order to minimize the loss of protons and the generation of secondary neutrons. The neutron occurrence rate and the number of protons that pass through the nozzle were analyzed by using a Particle and Heavy Ion Transport code System (PHITS) program in order to identify the nozzle that generated the strongest proton beam.

Comparison between experimental data and Monte-Carlo simulations of neutron production in spallation reactions of 0.7-1.5 GeV protons on a thick, lead target

NASA Astrophysics Data System (ADS)

Krása, A.; Majerle, M.; Krízek, F.; Wagner, V.; Kugler, A.; Svoboda, O.; Henzl, V.; Henzlová, D.; Adam, J.; Caloun, P.; Kalinnikov, V. G.; Krivopustov, M. I.; Stegailov, V. I.; Tsoupko-Sitnikov, V. M.

2006-05-01

Relativistic protons with energies 0.7-1.5 GeV interacting with a thick, cylindrical, lead target, surrounded by a uranium blanket and a polyethylene moderator, produced spallation neutrons. The spatial and energetic distributions of the produced neutron field were measured by the Activation Analysis Method using Al, Au, Bi, and Co radio-chemical sensors. The experimental yields of isotopes induced in the sensors were compared with Monte-Carlo calculations performed with the MCNPX 2.4.0 code.

Neutron structure of human carbonic anhydrase II: a hydrogen-bonded water network "switch" is observed between pH 7.8 and 10.0.

PubMed

Fisher, Zoë; Kovalevsky, Andrey Y; Mustyakimov, Marat; Silverman, David N; McKenna, Robert; Langan, Paul

2011-11-08

The neutron structure of wild-type human carbonic anhydrase II at pH 7.8 has been determined to 2.0 Å resolution. Detailed analysis and comparison to the previously determined structure at pH 10.0 show important differences in the protonation of key catalytic residues in the active site as well as a rearrangement of the H-bonded water network. For the first time, a completed H-bonded network stretching from the Zn-bound solvent to the proton shuttling residue, His64, has been directly observed.

Solar cosmic ray hazard to interplanetary and earth-orbital space travel

NASA Technical Reports Server (NTRS)

Yucker, W. R.

1972-01-01

A statistical treatment of the radiation hazards to astronauts due to solar cosmic ray protons is reported to determine shielding requirements for solar proton events. More recent data are incorporated into the present analysis in order to improve the accuracy of the predicted mission fluence and dose. The effects of the finite data sample are discussed. Mission fluence and dose versus shield thickness data are presented for mission lengths up to 3 years during periods of maximum and minimum solar activity; these correspond to various levels of confidence that the predicted hazard will not be exceeded.

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

Ion Beam Facility at the University of Chile; Applications and Basic Research

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

Miranda, P. A.; Morales, J. R.; Cancino, S.

2010-08-04

The main characteristics of the ion beam facility based on a 3.75 MeV Van de Graaff accelerator at the University of Chile are described at this work. Current activities are mainly focused on the application of the Ion Beam Analysis techniques for environmental, archaeological, and material science analysis. For instance, Rutherford Backscattering Spectrometry (RBS) is applied to measure thin gold film thickness which are used to determine their resistivity and other electrical properties. At this laboratory the Proton Induced X-Ray Emission (PIXE) and Proton Elastic Scattering Analysis (PESA) methodologies are extensively used for trace element analysis of urban aerosols (Santiago,more » Ciudad de Mexico). A similar study is being carried out at the Antarctica Peninsula. Characterization studies on obsidian and vitreous dacite samples using PIXE has been also perform allowing to match some of these artifacts with geological source sites in Chile.Basic physics research is being carried out by measuring low-energy cross section values for the reactions {sup 63}Cu(d,p){sup 64}Cu and {sup Nat}Zn(p,x){sup 67}Ga. Both radionuclide {sup 64}Cu and {sup 67}Ga are required for applications in medicine. Ongoing stopping power cross section measurements of proton and alphas on Pd, Cu, Bi and Mylar are briefly discussed.« less

Ion Beam Facility at the University of Chile; Applications and Basic Research

NASA Astrophysics Data System (ADS)

Miranda, P. A.; Morales, J. R.; Cancino, S.; Dinator, M. I.; Donoso, N.; Sepúlveda, A.; Ortiz, P.; Rojas, S.

2010-08-01

The main characteristics of the ion beam facility based on a 3.75 MeV Van de Graaff accelerator at the University of Chile are described at this work. Current activities are mainly focused on the application of the Ion Beam Analysis techniques for environmental, archaeological, and material science analysis. For instance, Rutherford Backscattering Spectrometry (RBS) is applied to measure thin gold film thickness which are used to determine their resistivity and other electrical properties. At this laboratory the Proton Induced X-Ray Emission (PIXE) and Proton Elastic Scattering Analysis (PESA) methodologies are extensively used for trace element analysis of urban aerosols (Santiago, Ciudad de Mexico). A similar study is being carried out at the Antarctica Peninsula. Characterization studies on obsidian and vitreous dacite samples using PIXE has been also perform allowing to match some of these artifacts with geological source sites in Chile. Basic physics research is being carried out by measuring low-energy cross section values for the reactions 63Cu(d,p)64Cu and NatZn(p,x)67Ga. Both radionuclide 64Cu and 67Ga are required for applications in medicine. Ongoing stopping power cross section measurements of proton and alphas on Pd, Cu, Bi and Mylar are briefly discussed.

Theoretical and computational studies of renewable energy materials: Room temperature ionic liquids and proton exchange membranes

NASA Astrophysics Data System (ADS)

Feng, Shulu

2011-12-01

Two kinds of renewable energy materials, room temperature ionic liquids (RTILs) and proton exchange membranes (PEMs), especially Nafion, are studied by computational and theoretical approaches. The ultimate purpose of the present research is to design novel materials to meet the future energy demands. To elucidate the effect of alkyl side chain length and anion on the structure and dynamics of the mixtures, molecular dynamics (MD) simulations of three RTILs/water mixtures at various water mole fractions: 1-butyl-3-methylimidazolium (BMIM+)/BF4-, 1-octyl-3-methylimidazolium (OMIM+)/BF4-, and OMIM +/Cl- are performed. Replacing the BMIM + cation with OMIM+ results in stronger aggregation of the cations as well as a slower diffusion of the anions, and replacing the BF4- anion with Cl- alters the water distribution at low water mole fractions and slows diffusion of the mixtures. Potential experimental manifestations of these behaviors in both cases are provided. Proton solvation properties and transport mechanisms are studied in hydrated Nafion, by using the self-consistent multistate empirical valence bond (SCI-MS-EVB) method. It is found that by stabilizing a more Zundel-like (H5O 2+) structure in the first solvation shells, the solvation of excess protons, as well as the proton hydration structure are both influenced by the sulfonate groups. Hydrate proton-related hydrogen bond networks are observed to be more stable than those with water alone. In order to characterize the nature of the proton transport (PT), diffusive motion, Arrhenius activation energies, and transport pathways are calculated and analyzed. Analysis of diffusive motion suggests that (1) a proton-hopping mechanism dominates the proton transport for the studied water loading levels and (2) there is an obvious degree of anti-correlation between the proton hopping and the vehicular transport. The activation energy drops rapidly with an increasing water content when the water loading level is smaller than ˜ 10 H2O/SO 3-, which is consistent with experimental observations. The sulfonate groups are also found to have influence on the proton hopping directions. The temperature and water content effects on the PT pathways are also investigated. The morphological effects on proton solvation and transport in hydrated Nafion are investigated, by using the SCI-MS-EVB method. Two of the most significant morphological models of Nafion, the lamellar model and the cylinder model, are selected. The two models exhibit distinct PT patterns, which result in different proton diffusion rates. In both models, the interaction between protons and the sulfonate groups are proven to be the key to determining PT behavior. The proton solvation structure change as a function of the distance between protons and sulfonate groups has been analyzed. It is found that the increase of water cylinder radius or water layer height leads to the presence of more protons around the sulfonate groups. Furthermore, at a lower hydration level, the increased amount of protons around the sulfonate groups consists of more Zundel-like structures, which is influenced by the distinct morphological structures of Nafion.

Proof of principle study of the use of a CMOS active pixel sensor for proton radiography.

PubMed

Seco, Joao; Depauw, Nicolas

2011-02-01

Proof of principle study of the use of a CMOS active pixel sensor (APS) in producing proton radiographic images using the proton beam at the Massachusetts General Hospital (MGH). A CMOS APS, previously tested for use in s-ray radiation therapy applications, was used for proton beam radiographic imaging at the MGH. Two different setups were used as a proof of principle that CMOS can be used as proton imaging device: (i) a pen with two metal screws to assess spatial resolution of the CMOS and (ii) a phantom with lung tissue, bone tissue, and water to assess tissue contrast of the CMOS. The sensor was then traversed by a double scattered monoenergetic proton beam at 117 MeV, and the energy deposition inside the detector was recorded to assess its energy response. Conventional x-ray images with similar setup at voltages of 70 kVp and proton images using commercial Gafchromic EBT 2 and Kodak X-Omat V films were also taken for comparison purposes. Images were successfully acquired and compared to x-ray kVp and proton EBT2/X-Omat film images. The spatial resolution of the CMOS detector image is subjectively comparable to the EBT2 and Kodak X-Omat V film images obtained at the same object-detector distance. X-rays have apparent higher spatial resolution than the CMOS. However, further studies with different commercial films using proton beam irradiation demonstrate that the distance of the detector to the object is important to the amount of proton scatter contributing to the proton image. Proton images obtained with films at different distances from the source indicate that proton scatter significantly affects the CMOS image quality. Proton radiographic images were successfully acquired at MGH using a CMOS active pixel sensor detector. The CMOS demonstrated spatial resolution subjectively comparable to films at the same object-detector distance. Further work will be done in order to establish the spatial and energy resolution of the CMOS detector for protons. The development and use of CMOS in proton radiography could allow in vivo proton range checks, patient setup QA, and real-time tumor tracking.

Development of activity pencil beam algorithm using measured distribution data of positron emitter nuclei generated by proton irradiation of targets containing (12)C, (16)O, and (40)Ca nuclei in preparation of clinical application.

PubMed

Miyatake, Aya; Nishio, Teiji; Ogino, Takashi

2011-10-01

The purpose of this study is to develop a new calculation algorithm that is satisfactory in terms of the requirements for both accuracy and calculation time for a simulation of imaging of the proton-irradiated volume in a patient body in clinical proton therapy. The activity pencil beam algorithm (APB algorithm), which is a new technique to apply the pencil beam algorithm generally used for proton dose calculations in proton therapy to the calculation of activity distributions, was developed as a calculation algorithm of the activity distributions formed by positron emitter nuclei generated from target nuclear fragment reactions. In the APB algorithm, activity distributions are calculated using an activity pencil beam kernel. In addition, the activity pencil beam kernel is constructed using measured activity distributions in the depth direction and calculations in the lateral direction. (12)C, (16)O, and (40)Ca nuclei were determined as the major target nuclei that constitute a human body that are of relevance for calculation of activity distributions. In this study, "virtual positron emitter nuclei" was defined as the integral yield of various positron emitter nuclei generated from each target nucleus by target nuclear fragment reactions with irradiated proton beam. Compounds, namely, polyethylene, water (including some gelatin) and calcium oxide, which contain plenty of the target nuclei, were irradiated using a proton beam. In addition, depth activity distributions of virtual positron emitter nuclei generated in each compound from target nuclear fragment reactions were measured using a beam ON-LINE PET system mounted a rotating gantry port (BOLPs-RGp). The measured activity distributions depend on depth or, in other words, energy. The irradiated proton beam energies were 138, 179, and 223 MeV, and measurement time was about 5 h until the measured activity reached the background level. Furthermore, the activity pencil beam data were made using the activity pencil beam kernel, which was composed of the measured depth data and the lateral data including multiple Coulomb scattering approximated by the Gaussian function, and were used for calculating activity distributions. The data of measured depth activity distributions for every target nucleus by proton beam energy were obtained using BOLPs-RGp. The form of the depth activity distribution was verified, and the data were made in consideration of the time-dependent change of the form. Time dependence of an activity distribution form could be represented by two half-lives. Gaussian form of the lateral distribution of the activity pencil beam kernel was decided by the effect of multiple Coulomb scattering. Thus, the data of activity pencil beam involving time dependence could be obtained in this study. The simulation of imaging of the proton-irradiated volume in a patient body using target nuclear fragment reactions was feasible with the developed APB algorithm taking time dependence into account. With the use of the APB algorithm, it was suggested that a system of simulation of activity distributions that has levels of both accuracy and calculation time appropriate for clinical use can be constructed.

Energy- and time-resolved detection of prompt gamma-rays for proton range verification.

PubMed

Verburg, Joost M; Riley, Kent; Bortfeld, Thomas; Seco, Joao

2013-10-21

In this work, we present experimental results of a novel prompt gamma-ray detector for proton beam range verification. The detection system features an actively shielded cerium-doped lanthanum(III) bromide scintillator, coupled to a digital data acquisition system. The acquisition was synchronized to the cyclotron radio frequency to separate the prompt gamma-ray signals from the later-arriving neutron-induced background. We designed the detector to provide a high energy resolution and an effective reduction of background events, enabling discrete proton-induced prompt gamma lines to be resolved. Measuring discrete prompt gamma lines has several benefits for range verification. As the discrete energies correspond to specific nuclear transitions, the magnitudes of the different gamma lines have unique correlations with the proton energy and can be directly related to nuclear reaction cross sections. The quantification of discrete gamma lines also enables elemental analysis of tissue in the beam path, providing a better prediction of prompt gamma-ray yields. We present the results of experiments in which a water phantom was irradiated with proton pencil-beams in a clinical proton therapy gantry. A slit collimator was used to collimate the prompt gamma-rays, and measurements were performed at 27 positions along the path of proton beams with ranges of 9, 16 and 23 g cm(-2) in water. The magnitudes of discrete gamma lines at 4.44, 5.2 and 6.13 MeV were quantified. The prompt gamma lines were found to be clearly resolved in dimensions of energy and time, and had a reproducible correlation with the proton depth-dose curve. We conclude that the measurement of discrete prompt gamma-rays for in vivo range verification of clinical proton beams is feasible, and plan to further study methods and detector designs for clinical use.

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

Depth profile of production yields of natPb(p, xn) 206,205,204,203,202,201Bi nuclear reactions

NASA Astrophysics Data System (ADS)

Mokhtari Oranj, Leila; Jung, Nam-Suk; Kim, Dong-Hyun; Lee, Arim; Bae, Oryun; Lee, Hee-Seock

2016-11-01

Experimental and simulation studies on the depth profiles of production yields of natPb(p, xn) 206,205,204,203,202,201Bi nuclear reactions were carried out. Irradiation experiments were performed at the high-intensity proton linac facility (KOMAC) in Korea. The targets, irradiated by 100-MeV protons, were arranged in a stack consisting of natural Pb, Al, Au foils and Pb plates. The proton beam intensity was determined by activation analysis method using 27Al(p, 3p1n)24Na, 197Au(p, p1n)196Au, and 197Au(p, p3n)194Au monitor reactions and also by Gafchromic film dosimetry method. The yields of produced radio-nuclei in the natPb activation foils and monitor foils were measured by HPGe spectroscopy system. Monte Carlo simulations were performed by FLUKA, PHITS/DCHAIN-SP, and MCNPX/FISPACT codes and the calculated data were compared with the experimental results. A satisfactory agreement was observed between the present experimental data and the simulations.

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.

How the shape of an H-bonded network controls proton-coupled water activation in HONO formation.

PubMed

Relph, Rachael A; Guasco, Timothy L; Elliott, Ben M; Kamrath, Michael Z; McCoy, Anne B; Steele, Ryan P; Schofield, Daniel P; Jordan, Kenneth D; Viggiano, Albert A; Ferguson, Eldon E; Johnson, Mark A

2010-01-15

Many chemical reactions in atmospheric aerosols and bulk aqueous environments are influenced by the surrounding solvation shell, but the precise molecular interactions underlying such effects have rarely been elucidated. We exploited recent advances in isomer-specific cluster vibrational spectroscopy to explore the fundamental relation between the hydrogen (H)-bonding arrangement of a set of ion-solvating water molecules and the chemical activity of this ensemble. We find that the extent to which the nitrosonium ion (NO+)and water form nitrous acid (HONO) and a hydrated proton cluster in the critical trihydrate depends sensitively on the geometrical arrangement of the water molecules in the network. Theoretical analysis of these data details the role of the water network in promoting charge delocalization.

Impact of mutation on proton transfer reactions in ketosteroid isomerase: insights from molecular dynamics simulations.

PubMed

Chakravorty, Dhruva K; Hammes-Schiffer, Sharon

2010-06-02

The two proton transfer reactions catalyzed by ketosteroid isomerase (KSI) involve a dienolate intermediate stabilized by hydrogen bonds with Tyr14 and Asp99. Molecular dynamics simulations based on an empirical valence bond model are used to examine the impact of mutating these residues on the hydrogen-bonding patterns, conformational changes, and van der Waals and electrostatic interactions during the proton transfer reactions. While the rate constants for the two proton transfer steps are similar for wild-type (WT) KSI, the simulations suggest that the rate constant for the first proton transfer step is smaller in the mutants due to the significantly higher free energy of the dienolate intermediate relative to the reactant. The calculated rate constants for the mutants D99L, Y14F, and Y14F/D99L relative to WT KSI are qualitatively consistent with the kinetic experiments indicating a significant reduction in the catalytic rates along the series of mutants. In the simulations, WT KSI retained two hydrogen-bonding interactions between the substrate and the active site, while the mutants typically retained only one hydrogen-bonding interaction. A new hydrogen-bonding interaction between the substrate and Tyr55 was observed in the double mutant, leading to the prediction that mutation of Tyr55 will have a greater impact on the proton transfer rate constants for the double mutant than for WT KSI. The electrostatic stabilization of the dienolate intermediate relative to the reactant was greater for WT KSI than for the mutants, providing a qualitative explanation for the significantly reduced rates of the mutants. The active site exhibited restricted motion during the proton transfer reactions, but small conformational changes occurred to facilitate the proton transfer reactions by strengthening the hydrogen-bonding interactions and by bringing the proton donor and acceptor closer to each other with the proper orientation for proton transfer. Thus, these calculations suggest that KSI forms a preorganized active site but that the structure of this preorganized active site is altered upon mutation. Moreover, small conformational changes due to stochastic thermal motions are required within this preorganized active site to facilitate the proton transfer reactions.

Randomized Clinical Trial Comparing Proton Beam Radiation Therapy with Transarterial Chemoembolization for Hepatocellular Carcinoma: Results of an Interim Analysis

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

Bush, David A., E-mail: dbush@llu.edu; Smith, Jason C.; Slater, Jerry D.

2016-05-01

Purpose: To describe results of a planned interim analysis of a prospective, randomized clinical trial developed to compare treatment outcomes among patients with newly diagnosed hepatocellular carcinoma (HCC). Methods and Materials: Eligible subjects had either clinical or pathologic diagnosis of HCC and met either Milan or San Francisco transplant criteria. Patients were randomly assigned to transarterial chemoembolization (TACE) or to proton beam radiation therapy. Patients randomized to TACE received at least 1 TACE with additional TACE for persistent disease. Proton beam radiation therapy was delivered to all areas of gross disease to a total dose of 70.2 Gy in 15 daily fractionsmore » over 3 weeks. The primary endpoint was progression-free survival, with secondary endpoints of overall survival, local tumor control, and treatment-related toxicities as represented by posttreatment days of hospitalization. Results: At the time of this analysis 69 subjects were available for analysis. Of these, 36 were randomized to TACE and 33 to proton. Total days of hospitalization within 30 days of TACE/proton was 166 and 24 days, respectively (P<.001). Ten TACE and 12 proton patients underwent liver transplantation after treatment. Viable tumor identified in the explanted livers after TACE/proton averaged 2.4 and 0.9 cm, respectively. Pathologic complete response after TACE/proton was 10%/25% (P=.38). The 2-year overall survival for all patients was 59%, with no difference between treatment groups. Median survival time was 30 months (95% confidence interval 20.7-39.3 months). There was a trend toward improved 2-year local tumor control (88% vs 45%, P=.06) and progression-free survival (48% vs 31%, P=.06) favoring the proton beam treatment group. Conclusions: This interim analysis indicates similar overall survival rates for proton beam radiation therapy and TACE. There is a trend toward improved local tumor control and progression-free survival with proton beam. There are significantly fewer hospitalization days after proton treatment, which may indicate reduced toxicity with proton beam therapy.« less

Induction of Cell Death through Alteration of Oxidants and Antioxidants in Epithelial Cells Exposed to High Energy Protons

NASA Technical Reports Server (NTRS)

Ramesh, Govindarajan; Wu, Honglu

2012-01-01

Radiation affects several cellular and molecular processes including double strand breakage, modifications of sugar moieties and bases. In outer space, protons are the primary radiation source which poses a range of potential health risks to astronauts. On the other hand, the use of proton radiation for tumor radiation therapy is increasing as it largely spares healthy tissues while killing tumor tissues. Although radiation related research has been conducted extensively, the molecular toxicology and cellular mechanisms affected by proton radiation remain poorly understood. Therefore, in the present study, we irradiated rat epithelial cells (LE) with different doses of protons and investigated their effects on cell proliferation and cell death. Our data showed an inhibition of cell proliferation in proton irradiated cells with a significant dose dependent activation and repression of reactive oxygen species (ROS) and antioxidants, glutathione and superoxide dismutase respectively as compared to control cells. In addition, apoptotic related genes such as caspase-3 and -8 activities were induced in a dose dependent manner with corresponding increased levels of DNA fragmentation in proton irradiated cells than control cells. Together, our results show that proton radiation alters oxidant and antioxidant levels in the cells to activate apoptotic pathway for cell death.

Tunneling Kinetics and Nonadiabatic Proton-Coupled Electron Transfer in Proteins: The Effect of Electric Fields and Anharmonic Donor-Acceptor Interactions.

PubMed

Salna, Bridget; Benabbas, Abdelkrim; Russo, Douglas; Champion, Paul M

2017-07-20

A proper description of proton donor-acceptor (D-A) distance fluctuations is crucial for understanding tunneling in proton-coupled electron transport (PCET). The typical harmonic approximation for the D-A potential results in a Gaussian probability distribution, which does not appropriately reflect the electronic repulsion forces that increase the energetic cost of sampling shorter D-A distances. Because these shorter distances are the primary channel for thermally activated tunneling, the analysis of tunneling kinetics depends sensitively on the inherently anharmonic nature of the D-A interaction. Thus, we have used quantum chemical calculations to account for the D-A interaction and developed an improved model for the analysis of experimental tunneling kinetics. Strong internal electric fields are also considered and found to contribute significantly to the compressive forces when the D-A distance distribution is positioned below the van der Waals contact distance. This model is applied to recent experiments on the wild type (WT) and a double mutant (DM) of soybean lipoxygenase-1 (SLO). The compressive force necessary to prepare the tunneling-active distribution in WT SLO is found to fall in the ∼ nN range, which greatly exceeds the measured values of molecular motor and protein unfolding forces. This indicates that ∼60-100 MV/cm electric fields, aligned along the D-A bond axis, must be generated by an enzyme conformational interconversion that facilitates the PCET tunneling reaction. Based on the absolute value of the measured tunneling rate, and using previously calculated values of the electronic matrix element, the population of this tunneling-active conformation is found to lie in the range 10 -5 -10 -7 , indicating this is a rare structural fluctuation that falls well below the detection threshold of recent ENDOR experiments. Additional analysis of the DM tunneling kinetics leads to a proposal that a disordered (high entropy) conformation could be tunneling-active due to its broad range of sampled D-A distances.

Sequential Proton Loss Electron Transfer in Deactivation of Iron(IV) Binding Protein by Tyrosine Based Food Components.

PubMed

Tang, Ning; Skibsted, Leif H

2017-08-02

The iron(IV) binding protein ferrylmyoglobin, MbFe(IV)═O, was found to be reduced by tyrosine based food components in aqueous solution through a sequential proton loss electron transfer reaction mechanism without binding to the protein as confirmed by isothermal titration calorimetry. Dopamine and epinephrine are the most efficient food components reducing ferrylmyoglobin to oxymyoglobin, MbFe(II)O 2 , and metmyoglobin, MbFe(III), as revealed by multivariate curve resolution alternating least-squares with second order rate constants of 33.6 ± 2.3 L/mol/s (ΔH ⧧ of 19 ± 5 kJ/mol, ΔS ⧧ of -136 ± 18 J/mol K) and 228.9 ± 13.3 L/mol/s (ΔH ⧧ of 110 ± 7 kJ/mol, ΔS ⧧ of 131 ± 25 J/mol K), respectively, at pH 7.4 and 25 °C. The other tyrosine based food components were found to reduce ferrylmyoglobin to metmyoglobin with similar reduction rates at pH 7.4 and 25 °C. These reduction reactions were enhanced by protonation of ferrylmyoglobin and facilitated proton transfer at acidic conditions. Enthalpy-entropy compensation effects were observed for the activation parameters (ΔH ⧧ and ΔS ⧧ ), indicating the common reaction mechanism. Moreover, principal component analysis combined with heat map were performed to understand the relationship between density functional theory calculated molecular descriptors and kinetic data, which was further modeled by partial least squares for quantitative structure-activity relationship analysis. In addition, a three tyrosine residue containing protein, lysozyme, was also found to be able to reduce ferrylmyoglobin with a second order rate constant of 66 ± 28 L/mol/s as determined by a competitive kinetic method.

Activation calculations for trapped protons below 200 MeV: Appendix

NASA Technical Reports Server (NTRS)

Laird, C. E.

1991-01-01

Tables are given displaying of the results of the activation calculations of metal samples and other material aboard the Long Duration Exposure Facility-1 (LDEF-1) and Spacelab-2 with the computer program, PTRAP4. The computer printouts give the reaction, the reactant product, the proton reaction cross sections as a function of the energy of the incident protons, and the activation as a function of distance into the sample from the exposed surface.

Functional elements in the minimal promoter of the human proton-coupled folate transporter

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

Stark, Michal; Gonen, Nitzan; Assaraf, Yehuda G., E-mail: assaraf@tx.technion.ac.il

2009-10-09

The proton-coupled folate transporter (PCFT) is the dominant intestinal folate transporter, however, its promoter has yet to be revealed. Hence, we here cloned a 3.1 kb fragment upstream to the first ATG of the human PCFT gene and generated sequential deletion constructs evaluated in luciferase reporter assay. This analysis mapped the minimal promoter to 157 bp upstream to the first ATG. Crucial GC-box sites were identified within the minimal promoter and in its close vicinity which substantially contribute to promoter activity, as their disruption resulted in 94% loss of luciferase activity. We also identified upstream enhancer elements including YY1 andmore » AP1 which, although distantly located, prominently transactivated the minimal promoter, as their inactivation resulted in 50% decrease in reporter activity. This is the first functional identification of the minimal PCFT promoter harboring crucial GC-box elements that markedly contribute to its transcriptional activation via putative interaction with distal YY1 and AP1 enhancer elements.« less

Critical Role for the Protons in FRTL-5 Thyroid Cells: Nuclear Sphingomyelinase Induced-Damage

PubMed Central

Albi, Elisabetta; Perrella, Giuseppina; Lazzarini, Andrea; Cataldi, Samuela; Lazzarini, Remo; Floridi, Alessandro; Ambesi-Impiombato, Francesco Saverio; Curcio, Francesco

2014-01-01

Proliferating thyroid cells are more sensitive to UV-C radiations than quiescent cells. The effect is mediated by nuclear phosphatidylcholine and sphingomyelin metabolism. It was demonstrated that proton beams arrest cell growth and stimulate apoptosis but until now there have been no indications in the literature about their possible mechanism of action. Here we studied the effect of protons on FRTL-5 cells in culture. We showed that proton beams stimulate slightly nuclear neutral sphingomyelinase activity and inhibit nuclear sphingomyelin-synthase activity in quiescent cells whereas stimulate strongly nuclear neutral sphingomyelinase activity and do not change nuclear sphingomyelin-synthase activity in proliferating cells. The study of neutral sphingomyelinase/sphingomyelin-synthase ratio, a marker of functional state of the cells, indicated that proton beams induce FRTL-5 cells in a proapoptotic state if the cells are quiescent and in an initial apoptotic state if the cells are proliferating. The changes of cell life are accompanied by a decrease of nuclear sphingomyelin and increase of bax protein. PMID:24979136

{sup 14}C depth profiles in Apollo 15 and 17 cores and lunar rock 68815

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

Jull, A.J.T.; Cloudt, S.; Donahue, D.J.

1998-09-01

Accelerator mass spectrometry (AMS) was used to measure the activity vs. depth profiles of {sup 14}C produced by both solar cosmic rays (SCR) and galactic cosmic rays (GCR) in Apollo 15 lunar cores 15001-6 and 15008, Apollo 17 core 76001, and lunar rock 68815. Calculated GCR production rates are in good agreement with {sup 14}C measurements at depths below {approximately}10 cm. Carbon-14 produced by solar protons was observed in the top few cm of the Apollo 15 cores and lunar rock 68815, with near-surface values as high as 66 dpm/kg in 68815. Only low levels of SCR-produced {sup 14}C weremore » observed in the Apollo 17 core 76001. New cross sections for production of {sup 14}C by proton spallation on O, Si, Al, Mg, Fe, and Ni were measured using AMS. These cross sections are essential for the analysis of the measured {sup 14}C depth profiles. The best fit to the activity-depth profiles for solar-proton-produced {sup 14}C measured in the tops of both the Apollo 15 cores and 68815 was obtained for an exponential rigidity spectral shape R{sub 0} of 110--115 MV and a 4 {pi} flux (J{sub 10}, Ep > 10 MeV) of 103--108 protons/cm{sup 2}/s. These values of R{sub 0} are higher, indicating a harder rigidity, and the solar-proton fluxes are higher than those determined from {sup 10}Be, {sup 26}Al, and {sup 53}Mn measurements.« less

Proton and non-proton activation of ASIC channels

PubMed Central

Gautschi, Ivan; van Bemmelen, Miguel Xavier; Schild, Laurent

2017-01-01

The Acid-Sensing Ion Channels (ASIC) exhibit a fast desensitizing current when activated by pH values below 7.0. By contrast, non-proton ligands are able to trigger sustained ASIC currents at physiological pHs. To analyze the functional basis of the ASIC desensitizing and sustained currents, we have used ASIC1a and ASIC2a mutants with a cysteine in the pore vestibule for covalent binding of different sulfhydryl reagents. We found that ASIC1a and ASIC2a exhibit two distinct currents, a proton-induced desensitizing current and a sustained current triggered by sulfhydryl reagents. These currents differ in their pH dependency, their sensitivity to the sulfhydryl reagents, their ionic selectivity and their relative magnitude. We propose a model for ASIC1 and ASIC2 activity where the channels can function in two distinct modes, a desensitizing mode and a sustained mode depending on the activating ligands. The pore vestibule of the channel represents a functional site for binding non-proton ligands to activate ASIC1 and ASIC2 at neutral pH and to prevent channel desensitization. PMID:28384246

Kinetics and mechanism of S-nitrosothiol acid-catalyzed hydrolysis: sulfur activation promotes facile NO+ release.

PubMed

Moran, Ernesto E; Timerghazin, Qadir K; Kwong, Elizabeth; English, Ann M

2011-03-31

The denitrosation of three primary S-nitrosothiols (RSNO; S-nitrosocysteine, S-nitroso-N-acetylcysteine, and S-nitrosoglutathione) and two tertiary RSNOs (S-nitrosopenicillamine and S-nitroso-N-acetylpenicillamine) was investigated in 3.75 M H(2)SO(4) to probe the mechanism of acid-catalyzed RSNO hydrolysis and its dependence on RSNO structure. This reversible reaction was forced to proceed in the denitrosation direction by trapping the nitrosating agent with HN(3). The primary RSNOs exhibited hydrolysis k(obs) values of ∼2 × 10(-4) s(-1), and the tertiary RSNO k(obs) values were an order of magnitude higher. Product analysis by HPLC revealed that the parent thiols (RSHs) were formed in 90-100% yield on 79-99% RSNO denitrosation. Possible hydrolysis mechanisms were studied computationally at the CBS-QB3 level using S-nitrosomethanethiol (MeSNO) as a model RSNO. Consideration of RSNOs as a combination of conventional R-S-N═O, zwitterionic R-S(+)═N-O(-), and RS(-)/NO(+) ion-pair resonance structures was key in understanding the mechanistic details of acid-catalyzed hydrolysis. Protonation of the S-nitroso oxygen or nitrogen activates the sulfur and nucleophilic attack by H(2)O at this atom leads to the formation of the sulfoxide-protonated N-hydroxysulfinamide, MeS(+)(OH)NHOH, with barriers of 19 and 29 kcal/mol, respectively. Proton loss and reprotonation at the nitrogen lead to secondary hydrolysis that produces the sulfinic acid MeS(═O)OH and NH(2)OH. Notably, no low-energy RSNO hydrolysis pathway for HNO release was found in the computational analysis. Protonation of the S-nitroso sulfur gives rise to NO(+) release with a low activation barrier (ΔH(double dagger)(calc) ≈ 6 kcal/mol) and the formation of MeSH in agreement with experiment. The experimental k(obs) can be expressed as K(a)k(1), where K(a) is the acid dissociation constant for protonation of the S-nitroso sulfur and k(1) the pseudo-first-order hydrolysis rate constant. Given the low ΔH(double dagger)(calc) for denitrosation of the S-protonated isomer, the observed slow rates of acid-catalyzed RSNO hydrolysis must be controlled by the magnitude of K(a). The 10-fold higher K(a) calculated for Me(3)CS(H(+))NO (∼10(-15)) compared to MeS(H(+))NO (10(-16)) is consistent with the order of magnitude larger k(obs) reported here for the tertiary vs primary RSNOs.

The molecular basis for species-specific activation of human TRPA1 protein by protons involves poorly conserved residues within transmembrane domains 5 and 6.

PubMed

de la Roche, Jeanne; Eberhardt, Mirjam J; Klinger, Alexandra B; Stanslowsky, Nancy; Wegner, Florian; Koppert, Wolfgang; Reeh, Peter W; Lampert, Angelika; Fischer, Michael J M; Leffler, Andreas

2013-07-12

The surveillance of acid-base homeostasis is concerted by diverse mechanisms, including an activation of sensory afferents. Proton-evoked activation of rodent sensory neurons is mainly mediated by the capsaicin receptor TRPV1 and acid-sensing ion channels. In this study, we demonstrate that extracellular acidosis activates and sensitizes the human irritant receptor TRPA1 (hTRPA1). Proton-evoked membrane currents and calcium influx through hTRPA1 occurred at physiological acidic pH values, were concentration-dependent, and were blocked by the selective TRPA1 antagonist HC030031. Both rodent and rhesus monkey TRPA1 failed to respond to extracellular acidosis, and protons even inhibited rodent TRPA1. Accordingly, mouse dorsal root ganglion neurons lacking TRPV1 only responded to protons when hTRPA1 was expressed heterologously. This species-specific activation of hTRPA1 by protons was reversed in both mouse and rhesus monkey TRPA1 by exchange of distinct residues within transmembrane domains 5 and 6. Furthermore, protons seem to interact with an extracellular interaction site to gate TRPA1 and not via a modification of intracellular N-terminal cysteines known as important interaction sites for electrophilic TRPA1 agonists. Our data suggest that hTRPA1 acts as a sensor for extracellular acidosis in human sensory neurons and should thus be taken into account as a yet unrecognized transduction molecule for proton-evoked pain and inflammation. The species specificity of this property is unique among known endogenous TRPA1 agonists, possibly indicating that evolutionary pressure enforced TRPA1 to inherit the role as an acid sensor in human sensory neurons.

The Molecular Basis for Species-specific Activation of Human TRPA1 Protein by Protons Involves Poorly Conserved Residues within Transmembrane Domains 5 and 6*

PubMed Central

de la Roche, Jeanne; Eberhardt, Mirjam J.; Klinger, Alexandra B.; Stanslowsky, Nancy; Wegner, Florian; Koppert, Wolfgang; Reeh, Peter W.; Lampert, Angelika; Fischer, Michael J. M.; Leffler, Andreas

2013-01-01

The surveillance of acid-base homeostasis is concerted by diverse mechanisms, including an activation of sensory afferents. Proton-evoked activation of rodent sensory neurons is mainly mediated by the capsaicin receptor TRPV1 and acid-sensing ion channels. In this study, we demonstrate that extracellular acidosis activates and sensitizes the human irritant receptor TRPA1 (hTRPA1). Proton-evoked membrane currents and calcium influx through hTRPA1 occurred at physiological acidic pH values, were concentration-dependent, and were blocked by the selective TRPA1 antagonist HC030031. Both rodent and rhesus monkey TRPA1 failed to respond to extracellular acidosis, and protons even inhibited rodent TRPA1. Accordingly, mouse dorsal root ganglion neurons lacking TRPV1 only responded to protons when hTRPA1 was expressed heterologously. This species-specific activation of hTRPA1 by protons was reversed in both mouse and rhesus monkey TRPA1 by exchange of distinct residues within transmembrane domains 5 and 6. Furthermore, protons seem to interact with an extracellular interaction site to gate TRPA1 and not via a modification of intracellular N-terminal cysteines known as important interaction sites for electrophilic TRPA1 agonists. Our data suggest that hTRPA1 acts as a sensor for extracellular acidosis in human sensory neurons and should thus be taken into account as a yet unrecognized transduction molecule for proton-evoked pain and inflammation. The species specificity of this property is unique among known endogenous TRPA1 agonists, possibly indicating that evolutionary pressure enforced TRPA1 to inherit the role as an acid sensor in human sensory neurons. PMID:23709225

Propensity and Risk Assessment for Solar Particle Events: Consideration of Integral Fluence at High Proton Energies

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee; Hayat, Matthew J.; Feiveson, alan H.; Cucinotta, Francis A.

2008-01-01

For future space missions with longer duration, exposure to large solar particle events (SPEs) with high energy levels is the major concern during extra-vehicular activities (EVAs) on the lunar and Mars surface. The expected SPE propensity for large proton fluence was estimated from a non-homogeneous Poisson model using the historical database for measurements of protons with energy > 30 MeV, Phi(sub 30). The database includes a continuous data set for the past 5 solar cycles. The resultant SPE risk analysis for a specific mission period was made including the 95% confidence level. In addition to total particle intensity of SPE, the detailed energy spectra of protons especially at high energy levels were recognized as extremely important parameter for the risk assessment, since there remains a significant cancer risks from those energetic particles for large events. Using all the recorded proton fluence of SPEs for energies >60 and >100 MeV, Phi(sub 60) and Phi(sub 100), respectively, the expected propensities of SPEs abundant with high energy protons were estimated from the same non-homogeneous Poisson model and the representative cancer risk was analyzed. The dependencies of risk with different energy spectra, for e.g. between soft and hard SPEs, were evaluated. Finally, we describe approaches to improve radiation protection of astronauts and optimize mission planning for future space missions.

Photocatalytic Conversion of Nitrobenzene to Aniline through Sequential Proton-Coupled One-Electron Transfers from a Cadmium Sulfide Quantum Dot

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

Jensen, Stephen C.; Bettis Homan, Stephanie; Weiss, Emily A.

2016-01-28

This paper describes the use of cadmium sulfide quantum dots (CdS QDs) as visible-light photocatalysts for the reduction of nitrobenzene to aniline through six sequential photoinduced, proton-coupled electron transfers. At pH 3.6–4.3, the internal quantum yield of photons-to-reducing electrons is 37.1% over 54 h of illumination, with no apparent decrease in catalyst activity. Monitoring of the QD exciton by transient absorption reveals that, for each step in the catalytic cycle, the sacrificial reductant, 3-mercaptopropionic acid, scavenges the excitonic hole in ~5 ps to form QD•–; electron transfer to nitrobenzene or the intermediates nitrosobenzene and phenylhydroxylamine then occurs on the nanosecondmore » time scale. The rate constants for the single-electron transfer reactions are correlated with the driving forces for the corresponding proton-coupled electron transfers. This result suggests, but does not prove, that electron transfer, not proton transfer, is rate-limiting for these reactions. Nuclear magnetic resonance analysis of the QD–molecule systems shows that the photoproduct aniline, left unprotonated, serves as a poison for the QD catalyst by adsorbing to its surface. Performing the reaction at an acidic pH not only encourages aniline to desorb but also increases the probability of protonated intermediates; the latter effect probably ensures that recruitment of protons is not rate-limiting.« less

Relevance of the Nuclear Quantum Effects on the Proton/Deuteron Transmission through Hexagonal Boron Nitride and Graphene Monolayers

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

Ekanayake, Niranji; Huang, Jingsong; Jakowski, Jacek

According to recent experiments, atomically thin hexagonal boron nitride and graphene are permeable to protons and deuterons (and not to other atomic species), and the experimental estimates of the activation energy are lower than the theoretical values by about 0.5 eV for the isolated proton-membrane transfer model. Our analysis of the electronic potential energy surfaces along the normal to the transmission direction, obtained using correlated electronic structure methods, suggests that the aqueous environment is essential to stabilize the proton { as opposed to the hydrogenatom { transmission. Therefore, the process is examined within a molecular model of H 2O {more » H(D) + { material { H 2O. Exact quantum-mechanical scattering calculations are performed to assess the relevance of the nuclear quantum eects, such as tunneling factors and the kinetic isotope eect (KIE). Deuteration is found to aect the thermal reaction rate constants (KIE of 3-4 for hexagonal boron nitride and 20-30 for the graphene) and to eectively lower the barriers to the proton transfer by 0.2 and 0.4 eV for the two membranes, respectively. This lowering eect is reduced for the deuteron by approximately a factor of three. A more comprehensive description of the proton transmission is likely to require an extended explicit aqueous environment.« less

Relevance of the Nuclear Quantum Effects on the Proton/Deuteron Transmission through Hexagonal Boron Nitride and Graphene Monolayers

DOE PAGES

Ekanayake, Niranji; Huang, Jingsong; Jakowski, Jacek; ...

2017-10-02

According to recent experiments, atomically thin hexagonal boron nitride and graphene are permeable to protons and deuterons (and not to other atomic species), and the experimental estimates of the activation energy are lower than the theoretical values by about 0.5 eV for the isolated proton-membrane transfer model. Our analysis of the electronic potential energy surfaces along the normal to the transmission direction, obtained using correlated electronic structure methods, suggests that the aqueous environment is essential to stabilize the proton { as opposed to the hydrogenatom { transmission. Therefore, the process is examined within a molecular model of H 2O {more » H(D) + { material { H 2O. Exact quantum-mechanical scattering calculations are performed to assess the relevance of the nuclear quantum eects, such as tunneling factors and the kinetic isotope eect (KIE). Deuteration is found to aect the thermal reaction rate constants (KIE of 3-4 for hexagonal boron nitride and 20-30 for the graphene) and to eectively lower the barriers to the proton transfer by 0.2 and 0.4 eV for the two membranes, respectively. This lowering eect is reduced for the deuteron by approximately a factor of three. A more comprehensive description of the proton transmission is likely to require an extended explicit aqueous environment.« less

Long-term mortality and cancer risk in irradiated rhesus monkeys

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

Wood, D.H.

1991-05-01

Continuous, 24-year observations on a group of 358 rhesus monkeys reveal that life shortening from exposure to protons in the energy range encountered in the Van Allen belts and solar proton events is influenced primarily by the dose rather than by the energy of radiation. Life shortening in groups exposed to similar surface doses of 138- to 2300-MeV and 32- to 55-MeV protons are not significantly different, but the low-energy protons are associated with more deaths in the early years, while the high-energy protons contribute more to mortality in later years. In males, the most significant cause of life shorteningmore » is nonleukemia cancers. In females, radiation increased the risk of endometriosis (an abnormal proliferation of the lining of the uterus) which resulted in significant mortality in the years before early detection and treatment methods were employed. Animals exposed to 55-MeV protons had a high incidence of malignant brain tumors with latent periods ranging from 13 months to 20 years. The first fatal cancer among nonirradiated controls occurred 18 years after the study began. Analysis of the dose-response data supports the 1989 guidelines of the NCRP for maximum permissible radiation exposures in astronauts (NCRP, Guidance on Radiation Received in Space Activities, Report No. 98, National Council on Radiation Protection and Measurements, Bethesda, MD, 1989).« less

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

Ichijo, Yuta; Mochimaru, Yuta; Azuma, Morio

Human G2A is activated by various stimuli such as lysophosphatidylcholine (LPC), 9-hydroxyoctadecadienoic acid (9-HODE), and protons. The receptor is coupled to multiple intracellular signaling pathways, including the G{sub s}-protein/cAMP/CRE, G{sub 12/13}-protein/Rho/SRE, and G{sub q}-protein/phospholipase C/NFAT pathways. In the present study, we examined whether zebrafish G2A homologs (zG2A-a and zG2A-b) could respond to these stimuli and activate multiple intracellular signaling pathways. We also examined whether histidine residue and basic amino acid residue in the N-terminus of the homologs also play roles similar to those played by human G2A residues if the homologs sense protons. We found that the zG2A-a showed themore » high CRE, SRE, and NFAT activities, however, zG2A-b showed only the high SRE activity under a pH of 8.0. Extracellular acidification from pH 7.4 to 6.3 ameliorated these activities in zG2A-a-expressing cells. On the other hand, acidification ameliorated the SRE activity but not the CRE and NFAT activities in zG2A-b-expressing cells. LPC or 9-HODE did not modify any activity of either homolog. The substitution of histidine residue at the 174{sup th} position from the N-terminus of zG2A-a to asparagine residue attenuated proton-induced CRE and NFAT activities but not SRE activity. The substitution of arginine residue at the 32nd position from the N-terminus of zG2A-a to the alanine residue also attenuated its high and the proton-induced CRE and NFAT activities. On the contrary, the substitution did not attenuate SRE activity. The substitution of the arginine residue at the 10th position from the N-terminus of zG2A-b to the alanine residue also did not attenuate its high or the proton-induced SRE activity. These results indicate that zebrafish G2A homologs were activated by protons but not by LPC and 9-HODE, and the activation mechanisms of the homologs were similar to those of human G2A. - Highlights: • Zebrafish two G2A homologs are proton-sensing receptors. • The signaling pathways activated by the homologs are different. • Histidine residues and basic amino acid residues critical for sensing protons are conserved.« less

Approach to the mechanism of hydrogen evolution electrocatalyzed by a model Co clathrochelate: A theoretical study by Density Functional Theory.

PubMed

Antuch Cubillas, Manuel; Millet, Pierre

2018-06-20

The hydrogen evolution reaction (HER) is the focus of much attention by the scientific community because of the increasing energetic demands of modern society for clean and renewable energy sources. Molecular complexes of 3d-transition metals, such as cobalt, are potential alternative candidates to platinum for the HER in acidic media. Among these, cage complexes such as tris-dioximate metal clathrochelates have shown high HER catalytic properties. However, it is not clear either the catalytic activity of this molecule is due to metal-centered activation of H+, due to a low oxidation state of the metal stabilized by the surrounding organic cage, or if it is the organic cage who has a further cooperative role in bringing protons together. In this work, we report on a DFT study of two possible mechanisms for the HER catalyzed by a model Co clathrochelate. In order to assess the putative ligand involvement in the mechanism, several protonation sites located in the organic cage along with several combinations of single and double protonation were investigated. This work further addressed two possible mechanisms for the HER. The structural and energetic analysis of relevant intermediates suggested that the electrocatalytic mechanism is not based on the cooperation between the ligand and the metal, but it is mainly due to the activation of H+ by the Co metallocenter. Our calculations further suggest that the last step in the mechanism is a proton coupled electron transfer step. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neutrino Charged Current Quasi-Elastic Analysis at MINERvA

NASA Astrophysics Data System (ADS)

Hurtado Anampa, Kenyi; Osta, Jyotsna

2014-03-01

MINERvA is a few GeV neutrino-nucleus scattering experiment designed to study low energy neutrino interactions both in support of neutrino oscillation experiments and as a pure weak probe of the nuclear medium. The experiment uses a fine-grained, high resolution detector. The active region is composed of plastic scintillator with additional targets of helium, carbon, iron, lead and water placed upstream of the active region. We present kinematic distributions from the double differential cross section analysis that aims to study quasi-elastic scattering of neutrinos in the active region as a function of the muon and proton observables. This analysis will use the low energy neutrino dataset recorded from November 2009 to April 2012.

Spectral Response and Diagnostics of Biological Activity of Hydroxyl-Containing Aromatic Compounds

NASA Astrophysics Data System (ADS)

Tolstorozhev, G. B.; Mayer, G. V.; Bel'kov, M. V.; Shadyro, O. I.

2016-08-01

Using IR Fourier spectra and employing quantum-chemical calculations of electronic structure, spectra, and proton-acceptor properties, synthetic derivatives of aminophenol exhibiting biological activity in the suppression of herpes, influenza, and HIV viruses have been investigated from a new perspective, with the aim of establishing the spectral response of biological activity of the molecules. It has been experimentally established that the participation of the aminophenol hydroxyl group in intramolecular hydrogen bonds is characteristic of structures with antiviral properties. A quantum-chemical calculation of the proton-acceptor ability of the investigated aminophenol derivatives has shown that biologically active structures are characterized by a high proton-acceptor ability of oxygen of the hydroxyl group. A correlation that has been obtained among the formation of an intramolecular hydrogen bond, high proton-acceptor ability, and antiviral activity of substituted aminophenols enables us to predict the pharmacological properties of new medical preparations of the given class of compounds.

Investigation of phosphoserine and cytidine 5'-phosphate by heteronuclear two-dimensional spectroscopy: samples with strong proton coupling

NASA Astrophysics Data System (ADS)

Bolton, Philip H.

Heteronuclear two-dimensional magnetic resonance is a novel method for investigating the conformations of cellular phosphates. The two-dimensional proton spectra are detected indirectly via the phosphorus-31 nucleus and thus allow determination of proton chemical shifts and coupling constants in situations in which the normal proton spectrum is obscured. Previous investigations of cellular phosphates with relatively simple spin systems have shown that the two-dimensional proton spectrum can be readily related to the normal proton spectrum by subspectral analysis. The normal proton spectrum can be decomposed into two subspectra, one for each polarization of the phosphorus-31 nucleus. The two-dimensional spectrum arises from the difference between the subspectra, and the normal proton spectrum is the sum. This allows simulation of the two-dimensional spectra and hence determination of the proton chemical shifts and coupling constants. Many cellular phosphates of interest, such as 5'-nucleotides and phosphoserine, contain three protons coupled to the phosphorus which are strongly coupled to one another. These samples are amenable to the two-dimensional method and the straightforward subspectral analysis is preserved when a 90° pulse is applied to the protons in the magnetization transfer step. The two-dimensional proton spectra of the samples investigated here have higher resolution than the normal proton spectra, revealing spectral features not readily apparent in the normal proton spectra.

Proof of principle study of the use of a CMOS active pixel sensor for proton radiography

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

Seco, Joao; Depauw, Nicolas

2011-02-15

Purpose: Proof of principle study of the use of a CMOS active pixel sensor (APS) in producing proton radiographic images using the proton beam at the Massachusetts General Hospital (MGH). Methods: A CMOS APS, previously tested for use in s-ray radiation therapy applications, was used for proton beam radiographic imaging at the MGH. Two different setups were used as a proof of principle that CMOS can be used as proton imaging device: (i) a pen with two metal screws to assess spatial resolution of the CMOS and (ii) a phantom with lung tissue, bone tissue, and water to assess tissuemore » contrast of the CMOS. The sensor was then traversed by a double scattered monoenergetic proton beam at 117 MeV, and the energy deposition inside the detector was recorded to assess its energy response. Conventional x-ray images with similar setup at voltages of 70 kVp and proton images using commercial Gafchromic EBT 2 and Kodak X-Omat V films were also taken for comparison purposes. Results: Images were successfully acquired and compared to x-ray kVp and proton EBT2/X-Omat film images. The spatial resolution of the CMOS detector image is subjectively comparable to the EBT2 and Kodak X-Omat V film images obtained at the same object-detector distance. X-rays have apparent higher spatial resolution than the CMOS. However, further studies with different commercial films using proton beam irradiation demonstrate that the distance of the detector to the object is important to the amount of proton scatter contributing to the proton image. Proton images obtained with films at different distances from the source indicate that proton scatter significantly affects the CMOS image quality. Conclusion: Proton radiographic images were successfully acquired at MGH using a CMOS active pixel sensor detector. The CMOS demonstrated spatial resolution subjectively comparable to films at the same object-detector distance. Further work will be done in order to establish the spatial and energy resolution of the CMOS detector for protons. The development and use of CMOS in proton radiography could allow in vivo proton range checks, patient setup QA, and real-time tumor tracking.« less

Protonation-induced ultrafast torsional dynamics in 9-anthrylbenzimidazole: a pH activated molecular rotor.

PubMed

Nandi, Amitabha; Kushwaha, Archana; Das, Dipanwita; Ghosh, Rajib

2018-03-07

We report the photophysical properties and excited state dynamics of 9-anthrylbenzimidazole (ANBI) which exhibits protonation-induced molecular rotor properties. In contrast to the highly emissive behavior of neutral ANBI, protonation of the benzimidazole group of ANBI induces efficient nonradiative deactivation by ultrafast torsional motion around the bond connecting the anthracene and benzimidazole units, as revealed by ultrafast transient absorption and fluorescence spectroscopy. Contrary to viscosity-independent fluorescence of neutral dyes, protonated ANBI is shown to display linear variation of emission yield and lifetime with solvent viscosity. The protonation-induced molecular rotor properties in the studied system are shown to be driven by enhanced charge transfer and are corroborated by quantum chemical calculations. Potential application as a microviscosity sensor of acidic regions in a heterogeneous environment by these proton-activated molecular rotor properties of ANBI is discussed.

Correlating Humidity-Dependent Ionically Conductive Surface Area with Transport Phenomena in Proton-Exchange Membranes

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

He, Qinggang; Kusoglu, Ahmet; Lucas, Ivan T.

2011-08-01

The objective of this effort was to correlate the local surface ionic conductance of a Nafion? 212 proton-exchange membrane with its bulk and interfacial transport properties as a function of water content. Both macroscopic and microscopic proton conductivities were investigated at different relative humidity levels, using electrochemical impedance spectroscopy and current-sensing atomic force microscopy (CSAFM). We were able to identify small ion-conducting domains that grew with humidity at the surface of the membrane. Numerical analysis of the surface ionic conductance images recorded at various relative humidity levels helped determine the fractional area of ion-conducting active sites. A simple square-root relationshipmore » between the fractional conducting area and observed interfacial mass-transport resistance was established. Furthermore, the relationship between the bulk ionic conductivity and surface ionic conductance pattern of the Nafion? membrane was examined.« less

Proton Therapy Verification with PET Imaging

PubMed Central

Zhu, Xuping; Fakhri, Georges El

2013-01-01

Proton therapy is very sensitive to uncertainties introduced during treatment planning and dose delivery. PET imaging of proton induced positron emitter distributions is the only practical approach for in vivo, in situ verification of proton therapy. This article reviews the current status of proton therapy verification with PET imaging. The different data detecting systems (in-beam, in-room and off-line PET), calculation methods for the prediction of proton induced PET activity distributions, and approaches for data evaluation are discussed. PMID:24312147

Proton beam characterization in the experimental room of the Trento Proton Therapy facility

NASA Astrophysics Data System (ADS)

Tommasino, F.; Rovituso, M.; Fabiano, S.; Piffer, S.; Manea, C.; Lorentini, S.; Lanzone, S.; Wang, Z.; Pasini, M.; Burger, W. J.; La Tessa, C.; Scifoni, E.; Schwarz, M.; Durante, M.

2017-10-01

As proton therapy is becoming an established treatment methodology for cancer patients, the number of proton centres is gradually growing worldwide. The economical effort for building these facilities is motivated by the clinical aspects, but might be also supported by the potential relevance for the research community. Experiments with high-energy protons are needed not only for medical physics applications, but represent also an essential part of activities dedicated to detector development, space research, radiation hardness tests, as well as of fundamental research in nuclear and particle physics. Here we present the characterization of the beam line installed in the experimental room of the Trento Proton Therapy Centre (Italy). Measurements of beam spot size and envelope, range verification and proton flux were performed in the energy range between 70 and 228 MeV. Methods for reducing the proton flux from typical treatments values of 106-109 particles/s down to 101-105 particles/s were also investigated. These data confirm that a proton beam produced in a clinical centre build by a commercial company can be exploited for a broad spectrum of experimental activities. The results presented here will be used as a reference for future experiments.

Study on patient-induced radioactivity during proton treatment in hengjian proton medical facility.

PubMed

Wu, Qingbiao; Wang, Qingbin; Liang, Tianjiao; Zhang, Gang; Ma, Yinglin; Chen, Yu; Ye, Rong; Liu, Qiongyao; Wang, Yufei; Wang, Huaibao

2016-09-01

At present, increasingly more proton medical facilities have been established globally for better curative effect and less side effect in tumor treatment. Compared with electron and photon, proton delivers more energy and dose at its end of range (Bragg peak), and has less lateral scattering for its much larger mass. However, proton is much easier to produce neutron and induced radioactivity, which makes radiation protection for proton accelerators more difficult than for electron accelerators. This study focuses on the problem of patient-induced radioactivity during proton treatment, which has been ignored for years. However, we confirmed it is a vital factor for radiation protection to both patient escort and positioning technician, by FLUKA's simulation and activation formula calculation of Hengjian Proton Medical Facility (HJPMF), whose energy ranges from 130 to 230MeV. Furthermore, new formulas for calculating the activity buildup process of periodic irradiation were derived and used to study the relationship between saturation degree and half-life of nuclides. Finally, suggestions are put forward to lessen the radiation hazard from patient-induced radioactivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gate modulation of proton transport in a nanopore.

PubMed

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

2016-03-14

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

Energy release, beam attenuation radiation damage, gas production and accumulation of long-lived activity in Pb, Pb-Bi and Hg targets

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

Shubin, Yu.N.

1996-06-01

The calculation and analysis of the nuclei concentrations and long-lived residual radioactivity accumulated in Pb, Pb-Bi and Hg targets irradiated by 800 MeV, 30 mA proton beam have been performed. The dominating components to the total radioactivity of radionuclides resulting from fission and spallation reactions and radiative capture by both target nuclei and accumulated radioactive nuclei for various irradiation and cooling times were analyzed. The estimations of spectral component contributions of neutron and proton fluxes to the accumulated activity were carried out. The contributions of fission products to the targets activity and partial activities of main long-lived fission products tomore » the targets activity and partial activities of main long-lived fission products were evaluated. The accumulation of Po isotopes due to reactions induced by secondary alpha-particles were found to be important for the Pb target as compared with two-step radiative capture. The production of Tritium in the targets and its contribution to the total targets activity was considered in detail. It is found that total activities of both targets are close to one another.« less

Mechanism of pH-dependent activation of the sodium-proton antiporter NhaA

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Hydrogen concentration analysis in clinopyroxene using proton-proton scattering analysis

NASA Astrophysics Data System (ADS)

Weis, Franz A.; Ros, Linus; Reichart, Patrick; Skogby, Henrik; Kristiansson, Per; Dollinger, Günther

2018-02-01

Traditional methods to measure water in nominally anhydrous minerals (NAMs) are, for example, Fourier transformed infrared (FTIR) spectroscopy or secondary ion mass spectrometry (SIMS). Both well-established methods provide a low detection limit as well as high spatial resolution yet may require elaborate sample orientation or destructive sample preparation. Here we analyze the water content in erupted volcanic clinopyroxene phenocrysts by proton-proton scattering and reproduce water contents measured by FTIR spectroscopy. We show that this technique provides significant advantages over other methods as it can provide a three-dimensional distribution of hydrogen within a crystal, making the identification of potential inclusions possible as well as elimination of surface contamination. The sample analysis is also independent of crystal structure and orientation and independent of matrix effects other than sample density. The results are used to validate the accuracy of wavenumber-dependent vs. mineral-specific molar absorption coefficients in FTIR spectroscopy. In addition, we present a new method for the sample preparation of very thin crystals suitable for proton-proton scattering analysis using relatively low accelerator potentials.

NATALIE: A 32 detector integrated acquisition system to characterize laser produced energetic particles with nuclear techniques

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

Tarisien, M.; Plaisir, C.; Gobet, F.

2011-02-15

We present a stand-alone system to characterize the high-energy particles emitted in the interaction of ultrahigh intensity laser pulses with matter. According to the laser and target characteristics, electrons or protons are produced with energies higher than a few mega electron volts. Selected material samples can, therefore, be activated via nuclear reactions. A multidetector, named NATALIE, has been developed to count the {beta}{sup +} activity of these irradiated samples. The coincidence technique used, designed in an integrated system, results in very low background in the data, which is required for low activity measurements. It, therefore, allows a good precision onmore » the nuclear activation yields of the produced radionuclides. The system allows high counting rates and online correction of the dead time. It also provides, online, a quick control of the experiment. Geant4 simulations are used at different steps of the data analysis to deduce, from the measured activities, the energy and angular distributions of the laser-induced particle beams. Two applications are presented to illustrate the characterization of electrons and protons.« less

Dynamics of Intense Pulsed Proton Beam in the Nagaoka ETIGO-I

NASA Astrophysics Data System (ADS)

Tanaka, Hajime; Konno, Kohji; Masugata, Katsumi; Yatsui, Kiyoshi; Matsui, Masao

1982-10-01

Dynamics of an intense pulsed proton beam have been studied by measuring nuclear reactions as well as by a biased ion-collector (BIC). When the ion-current density (Ji) is small such that Ji<30 A/cm2, the proton number measured by BIC is in good agreement with that by nuclear activation. Good linearity exists between time integrated γ-ray signal and proton number measured by the activation. Hence, it would be possible to obtain the proton number quantitatively even when a target “blow-off” takes place at Ji>1 kA/cm2. Prompt γ-ray is also measured by the time-of-flight method to yield reasonable agreement with the applied peak potential.

Synthesis, crystal growth and characterization of bioactive material: 2- Amino-1H-benzimidazolium pyridine-3-carboxylate single crystal- a proton transfer molecular complex

NASA Astrophysics Data System (ADS)

Fathima, K. Saiadali; Kavitha, P.; Anitha, K.

2017-09-01

The 1:1 molecular adducts 2- Amino-1H-benzimidazolium pyridine-3-carboxylate (2ABPC) was synthesized and grown as single crystal where 2-aminobenzimidazole (ABI) acts as a donor and nicotinic acid (NA) acts as an acceptor. The presence of proton and carbon were predicted using 1H and 13C NMR spectral analysis. The molecular structure of the crystal was elucidated by subjecting the grown crystals to the single crystal x-ray diffraction analysis and was refined by full matrix least-squares method to R = 0.038 for 2469 reflections. The vibrational modes of functional group have been studied using FTIR and Raman spectroscopic analysis. The UV-Vis spectrum exhibited a visible band at 246 nm for 2ABPC due to the nicotinate anion of the molecule. Further, the antimicrobial activity of 2ABPC complex against B. subtilis, klebsiella pneumonia, Pseudomonas eruginos and E. coli pathogens was investigated. Minimum Inhibitory Concentration (MIC) for this crystal was obtained using UV spectrometer against MRSA pathogen. It was found that the benzimidazole with aminogroup at position 2 increases the general antimicrobial activities of 2ABPC crystal.

Study of the effects of high-energy proton beams on escherichia coli

NASA Astrophysics Data System (ADS)

Park, Jeong Chan; Jung, Myung-Hwan

2015-10-01

Antibiotic-resistant bacterial infection is one of the most serious risks to public health care today. However, discouragingly, the development of new antibiotics has progressed little over the last decade. There is an urgent need for alternative approaches to treat antibiotic-resistant bacteria. Novel methods, which include photothermal therapy based on gold nano-materials and ionizing radiation such as X-rays and gamma rays, have been reported. Studies of the effects of high-energy proton radiation on bacteria have mainly focused on Bacillus species and its spores. The effect of proton beams on Escherichia coli (E. coli) has been limitedly reported. Escherichia coli is an important biological tool to obtain metabolic and genetic information and is a common model microorganism for studying toxicity and antimicrobial activity. In addition, E. coli is a common bacterium in the intestinal tract of mammals. In this research, the morphological and the physiological changes of E. coli after proton irradiation were investigated. Diluted solutions of cells were used for proton beam radiation. LB agar plates were used to count the number of colonies formed. The growth profile of the cells was monitored by using the optical density at 600 nm. The morphology of the irradiated cells was observed with an optical microscope. A microarray analysis was performed to examine the gene expression changes between irradiated samples and control samples without irradiation. E coli cells have observed to be elongated after proton irradiation with doses ranging from 13 to 93 Gy. Twenty-two were up-regulated more than twofold in proton-irradiated samples (93 Gy) compared with unexposed one.

A system for monitoring the radiation effects of a proton linear accelerator

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

Skorkin, V. M., E-mail: skorkin@inr.ru; Belyanski, K. L.; Skorkin, A. V.

2016-12-15

The system for real-time monitoring of radioactivity of a high-current proton linear accelerator detects secondary neutron emission from proton beam losses in transport channels and measures the activity of radionuclides in gas and aerosol emissions and the radiation background in the environment affected by a linear accelerator. The data provided by gamma, beta, and neutron detectors are transferred over a computer network to the central server. The system allows one to monitor proton beam losses, the activity of gas and aerosol emissions, and the radiation emission level of a linear accelerator in operation.

Proton: The Particle

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

Suit, Herman

The purpose of this article is to review briefly the nature of protons: creation at the Big Bang, abundance, physical characteristics, internal components, and life span. Several particle discoveries by proton as the experimental tool are considered. Protons play important roles in science, medicine, and industry. This article was prompted by my experience in the curative treatment of cancer patients by protons and my interest in the nature of protons as particles. The latter has been stimulated by many discussions with particle physicists and reading related books and journals. Protons in our universe number ≈10{sup 80}. Protons were created atmore » 10{sup −6} –1 second after the Big Bang at ≈1.37 × 10{sup 10} years beforethe present. Proton life span has been experimentally determined to be ≥10{sup 34} years; that is, the age of the universe is 10{sup −24}th of the minimum life span of a proton. The abundance of the elements is hydrogen, ≈74%; helium, ≈24%; and heavier atoms, ≈2%. Accordingly, protons are the dominant baryonic subatomic particle in the universe because ≈87% are protons. They are in each atom in our universe and thus involved in virtually every activity of matter in the visible universe, including life on our planet. Protons were discovered in 1919. In 1968, they were determined to be composed of even smaller particles, principally quarks and gluons. Protons have been the experimental tool in the discoveries of quarks (charm, bottom, and top), bosons (W{sup +}, W{sup −}, Z{sup 0}, and Higgs), antiprotons, and antineutrons. Industrial applications of protons are numerous and important. Additionally, protons are well appreciated in medicine for their role in radiation oncology and in magnetic resonance imaging. Protons are the dominant baryonic subatomic particle in the visible universe, comprising ≈87% of the particle mass. They are present in each atom of our universe and thus a participant in every activity involving matter.« less

Proton: the particle.

PubMed

Suit, Herman

2013-11-01

The purpose of this article is to review briefly the nature of protons: creation at the Big Bang, abundance, physical characteristics, internal components, and life span. Several particle discoveries by proton as the experimental tool are considered. Protons play important roles in science, medicine, and industry. This article was prompted by my experience in the curative treatment of cancer patients by protons and my interest in the nature of protons as particles. The latter has been stimulated by many discussions with particle physicists and reading related books and journals. Protons in our universe number ≈10(80). Protons were created at 10(-6) -1 second after the Big Bang at ≈1.37 × 10(10) years beforethe present. Proton life span has been experimentally determined to be ≥10(34) years; that is, the age of the universe is 10(-24)th of the minimum life span of a proton. The abundance of the elements is hydrogen, ≈74%; helium, ≈24%; and heavier atoms, ≈2%. Accordingly, protons are the dominant baryonic subatomic particle in the universe because ≈87% are protons. They are in each atom in our universe and thus involved in virtually every activity of matter in the visible universe, including life on our planet. Protons were discovered in 1919. In 1968, they were determined to be composed of even smaller particles, principally quarks and gluons. Protons have been the experimental tool in the discoveries of quarks (charm, bottom, and top), bosons (W(+), W(-), Z(0), and Higgs), antiprotons, and antineutrons. Industrial applications of protons are numerous and important. Additionally, protons are well appreciated in medicine for their role in radiation oncology and in magnetic resonance imaging. Protons are the dominant baryonic subatomic particle in the visible universe, comprising ≈87% of the particle mass. They are present in each atom of our universe and thus a participant in every activity involving matter. Copyright © 2013 Elsevier Inc. All rights reserved.

Analysis of proton wires in the enzyme active site suggests a mechanism of c-di-GMP hydrolysis by the EAL domain phosphodiesterases.

PubMed

Grigorenko, Bella L; Knyazeva, Marina A; Nemukhin, Alexander V

2016-11-01

We report for the first time a hydrolysis mechanism of the cyclic dimeric guanosine monophosphate (c-di-GMP) by the EAL domain phosphodiesterases as revealed by molecular simulations. A model system for the enzyme-substrate complex was prepared on the base of the crystal structure of the EAL domain from the BlrP1 protein complexed with c-di-GMP. The nucleophilic hydroxide generated from the bridging water molecule appeared in a favorable position for attack on the phosphorus atom of c-di-GMP. The most difficult task was to find a pathway for a proton transfer to the O3' atom of c-di-GMP to promote the O3'P bond cleavage. We show that the hydrogen bond network extended over the chain of water molecules in the enzyme active site and the Glu359 and Asp303 side chains provides the relevant proton wires. The suggested mechanism is consistent with the structural, mutagenesis, and kinetic experimental studies on the EAL domain phosphodiesterases. Proteins 2016; 84:1670-1680. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

SU-F-J-51: A Cone-Based Scintillator Detector for IGRT QA for Scattered and Scanning Proton Therapy

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

Oesten, H; Clasie, B; Jee, K

Purpose: IGRT commissioning and QA are critical components for precise delivery of proton treatment beams to patients. In order to ensure high quality IGRT, a new cone-based scintillator detector was evaluated for our QA activities for double-scattered and scanning proton modalities. This allows a routine evaluation of the gantry-angle dependent position offset between the radiation and imaging. Methods: The cone-based scintillator detector (XRV-124, Logos Systems, Int’l CA, USA) features a unique configuration of measuring stereotactic paths of proton and x-ray beams in a single setup with arbitrary gantry angles. For the beams-eye-view (BEV) analysis of x-ray crosshair images, a cylindricalmore » representation of the cone image was newly developed. The calibration accuracy was evaluated using different CT resolutions for a range of 55 – 95mm in patient’s cranial direction and ±9mm in the lateral direction. Energy-dependent spot sizes (σ) of pencil beams were characterized and compared to measurements by the MatriXX detector (IBA, Germany). Iso-centric deviations between radiation and x-ray imaging were characterized as a function of gantry angle. Results: The position calibration of the detector was successfully verified with a reproducible positioning by x-ray imaging. The measurements were reproducible within clinical tolerances (±1mm). The spot size vs. energy at zero gantry angle measured with the scintillating cone detector agreed with the MatriXX detector measurements within 17%. Conclusion: The new approach to investigate the accuracy of IGRT and pencil beam properties could successfully be implemented into the QA program. The system will improve efficiency in our QA activities for proton treatments.« less

Hybrid quantum chemical studies for the methanol formation reaction assisted by the proton transfer mechanism in supercritical water: CH3Cl+nH2O-->CH3OH+HCl+(n-1)H2O

NASA Astrophysics Data System (ADS)

Hori, T.; Takahashi, H.; Nitta, T.

2003-10-01

The proton transfer along the chain of hydrogen bonds is involved in many chemical reactions in aqueous solution and known to play a decisive role. We have performed the hybrid quantum chemical simulations for the methanol formation reaction catalyzed by the proton transfer mechanism [CH3Cl+nH2O→CH3OH+HCl+(n-1)H2O, n=3] in supercritical water (SCW) to investigate the role of water solvent on the reaction. In the simulation, the electronic state of the chemically active solutes (CH3Cl+3H2O) has been determined quantum mechanically, while the static water solvent has been represented by a classical model. The activation free energy for the water-catalytic reaction in SCW has been found to be 9.6 kcal/mol, which is much lower than that in the gas phase (29.2 kcal/mol). The fractional charge analysis has revealed that the notable charge separation in the solute complex takes place at the transition state (TS) and the resulting huge dipole gives rise to the considerable stabilization of the TS as compared to the reactant. It has been shown that the reaction assisted by the proton transfer mechanism is energetically much favored than the ionic SN2 reaction (CH3Cl+OH-→CH3OH+Cl-, 18.8 kcal/mol). The present calculations suggest that the proton migrations through the chain of hydrogen bonds can be regarded as a probable candidate responsible for the anomalous reactivities observed in SCW.

Quantum delocalization of protons in the hydrogen-bond network of an enzyme active site.

PubMed

Wang, Lu; Fried, Stephen D; Boxer, Steven G; Markland, Thomas E

2014-12-30

Enzymes use protein architectures to create highly specialized structural motifs that can greatly enhance the rates of complex chemical transformations. Here, we use experiments, combined with ab initio simulations that exactly include nuclear quantum effects, to show that a triad of strongly hydrogen-bonded tyrosine residues within the active site of the enzyme ketosteroid isomerase (KSI) facilitates quantum proton delocalization. This delocalization dramatically stabilizes the deprotonation of an active-site tyrosine residue, resulting in a very large isotope effect on its acidity. When an intermediate analog is docked, it is incorporated into the hydrogen-bond network, giving rise to extended quantum proton delocalization in the active site. These results shed light on the role of nuclear quantum effects in the hydrogen-bond network that stabilizes the reactive intermediate of KSI, and the behavior of protons in biological systems containing strong hydrogen bonds.

Quantum delocalization of protons in the hydrogen-bond network of an enzyme active site

PubMed Central

Wang, Lu; Fried, Stephen D.; Boxer, Steven G.; Markland, Thomas E.

2014-01-01

Enzymes use protein architectures to create highly specialized structural motifs that can greatly enhance the rates of complex chemical transformations. Here, we use experiments, combined with ab initio simulations that exactly include nuclear quantum effects, to show that a triad of strongly hydrogen-bonded tyrosine residues within the active site of the enzyme ketosteroid isomerase (KSI) facilitates quantum proton delocalization. This delocalization dramatically stabilizes the deprotonation of an active-site tyrosine residue, resulting in a very large isotope effect on its acidity. When an intermediate analog is docked, it is incorporated into the hydrogen-bond network, giving rise to extended quantum proton delocalization in the active site. These results shed light on the role of nuclear quantum effects in the hydrogen-bond network that stabilizes the reactive intermediate of KSI, and the behavior of protons in biological systems containing strong hydrogen bonds. PMID:25503367

PCDAQ, A Windows Based DAQ System

NASA Astrophysics Data System (ADS)

Hogan, Gary

1998-10-01

PCDAQ is a Windows NT based general DAQ/Analysis/Monte Carlo shell developed as part of the Proton Radiography project at LANL (Los Alamos National Laboratory). It has been adopted by experiments outside of the Proton Radiography project at Brookhaven National Laboratory (BNL) and at LANL. The program provides DAQ, Monte Carlo, and replay (disk file input) modes. Data can be read from hardware (CAMAC) or other programs (ActiveX servers). Future versions will read VME. User supplied data analysis routines can be written in Fortran, C++, or Visual Basic. Histogramming, testing, and plotting packages are provided. Histogram data can be exported to spreadsheets or analyzed in user supplied programs. Plots can be copied and pasted as bitmap objects into other Windows programs or printed. A text database keyed by the run number is provided. Extensive software control flags are provided so that the user can control the flow of data through the program. Control flags can be set either in script command files or interactively. The program can be remotely controlled and data accessed over the Internet through its ActiveX DCOM interface.

SU-F-I-70: Investigation of Gafchromic EBT3 Film Energy Dependence Using Proton, Photon, and Electron Beams

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

Ferreira, C; Schnell, E; Ahmad, S

Purpose: To investigate the energy dependence of Gafchromic EBT3 film over a range of clinically used proton, photon and electron energies. Methods: Proton beam energies of 117 and 204 MeV, corresponding respectively to ranges in water of 10 cm and 27 cm from a Mevion S250 double scatter system unit were used. Electron energies of 6 and 20 MeV and photon energies of 6 and 18 MV from a Varian Clinac 21EX Linac were used. Two pieces of film (5×5 cm{sup 2}) were irradiated sequentially for doses of 100, 500, and 1000 cGy for all energies and modalities. Films weremore » placed on the central beam axis for a 10×10 cm{sup 2} field size in the middle of spread out Bragg peak (SOBP) for proton and in respective dmax for photon and electron energies. Films were scanned on a flatbed Epson Expression 10000 XL scanner on the central region of the scanning window using 48-bit, 300 dpi, and landscape orientation after 48 hours post-irradiation of film to account for optical density (OD) stabilization. Film analysis of the red channel was performed using ImageJ 1.48v (National Institutes of Health). Results: The energy dependency of EBT3 among all energies and modalities for all doses studied was small within measurement uncertainties (1σ = ± 4.1%). The mean net OD in red channel for films receiving the same dose in the same energy modality had standard deviations within 0.9% for photons, 4.9% for electrons and 1.8% for protons. It was observed that film pieces were activated during proton irradiation, e.g., 7 mR/hr at surface after 30 minutes of irradiation, lasting for 2 hours post irradiation. Conclusion: EBT3 energy dependency was evaluated for clinically used proton, photon, and electron energies. The film self-activation may have contributed to fog and negligible dose.« less

Synthesis, crystal structure, antimicrobial activity and DNA-binding of hydrogen-bonded proton-transfer complex of 2,6-diaminopyridine with picric acid.

PubMed

Khan, Ishaat M; Ahmad, Afaq; Ullah, M F

2011-04-04

A proton-transfer (charge transfer) complex formed on the reaction between 2,6-diaminopyridine (donor) and picric acid (acceptor) was synthesized and characterized by FTIR, (1)H NMR, thermal and elemental analysis. The crystal structure determined by single-crystal X-ray diffraction indicates that cation and anion are joined together by strong N(+)-H- -O(-) type hydrogen bonds. The hydrogen-bonded charge transfer (HBCT) complex was screened for its pharmacology such as antimicrobial activity against various fungal and bacterial strains and Calf thymus DNA-binding. The results showed that HBCT complex (100μg/ml) exhibited good antibacterial antifungal activity as that of standard antibiotics Tetracycline and Nystatin. A molecular frame work through H-bonding interactions between neighboring moieties is found to be responsible for high melting point of resulting complex. This has been attributed to the formation of 1:1 HBCT complex. Copyright © 2011 Elsevier B.V. All rights reserved.

Upstream proton cyclotron waves at Venus near solar maximum

NASA Astrophysics Data System (ADS)

Delva, M.; Bertucci, C.; Volwerk, M.; Lundin, R.; Mazelle, C.; Romanelli, N.

2015-01-01

magnetometer data of Venus Express are analyzed for the occurrence of waves at the proton cyclotron frequency in the spacecraft frame in the upstream region of Venus, for conditions of rising solar activity. The data of two Venus years up to the time of highest sunspot number so far (1 Mar 2011 to 31 May 2012) are studied to reveal the properties of the waves and the interplanetary magnetic field (IMF) conditions under which they are observed. In general, waves generated by newborn protons from exospheric hydrogen are observed under quasi- (anti)parallel conditions of the IMF and the solar wind velocity, as is expected from theoretical models. The present study near solar maximum finds significantly more waves than a previous study for solar minimum, with an asymmetry in the wave occurrence, i.e., mainly under antiparallel conditions. The plasma data from the Analyzer of Space Plasmas and Energetic Atoms instrument aboard Venus Express enable analysis of the background solar wind conditions. The prevalence of waves for IMF in direction toward the Sun is related to the stronger southward tilt of the heliospheric current sheet for the rising phase of Solar Cycle 24, i.e., the "bashful ballerina" is responsible for asymmetric background solar wind conditions. The increase of the number of wave occurrences may be explained by a significant increase in the relative density of planetary protons with respect to the solar wind background. An exceptionally low solar wind proton density is observed during the rising phase of Solar Cycle 24. At the same time, higher EUV increases the ionization in the Venus exosphere, resulting in higher supply of energy from a higher number of newborn protons to the wave. We conclude that in addition to quasi- (anti)parallel conditions of the IMF and the solar wind velocity direction, the higher relative density of Venus exospheric protons with respect to the background solar wind proton density is the key parameter for the higher number of observable proton cyclotron waves near solar maximum.

Standardizing Activation Analysis: New Software for Photon Activation Analysis

NASA Astrophysics Data System (ADS)

Sun, Z. J.; Wells, D.; Segebade, C.; Green, J.

2011-06-01

Photon Activation Analysis (PAA) of environmental, archaeological and industrial samples requires extensive data analysis that is susceptible to error. For the purpose of saving time, manpower and minimizing error, a computer program was designed, built and implemented using SQL, Access 2007 and asp.net technology to automate this process. Based on the peak information of the spectrum and assisted by its PAA library, the program automatically identifies elements in the samples and calculates their concentrations and respective uncertainties. The software also could be operated in browser/server mode, which gives the possibility to use it anywhere the internet is accessible. By switching the nuclide library and the related formula behind, the new software can be easily expanded to neutron activation analysis (NAA), charged particle activation analysis (CPAA) or proton-induced X-ray emission (PIXE). Implementation of this would standardize the analysis of nuclear activation data. Results from this software were compared to standard PAA analysis with excellent agreement. With minimum input from the user, the software has proven to be fast, user-friendly and reliable.

Decision analytic modeling for the economic analysis of proton radiotherapy for non-small cell lung cancer

PubMed Central

Richard, Patrick J.; Zeng, Jing; Apisarnthanarax, Smith; Rengan, Ramesh; Phillips, Mark H.

2018-01-01

Background Although proton radiation treatments are more costly than photon/X-ray therapy, they may lower overall treatment costs through reducing rates of severe toxicities and the costly management of those toxicities. To study this issue, we created a decision-model comparing proton vs. X-ray radiotherapy for locally advanced non-small cell lung cancer patients. Methods An influence diagram was created to model for radiation delivery, associated 6-month pneumonitis/esophagitis rates, and overall costs (radiation plus toxicity costs). Pneumonitis (age, chemo type, V20, MLD) and esophagitis (V60) predictors were modeled to impact toxicity rates. We performed toxicity-adjusted, rate-adjusted, risk group-adjusted, and radiosensitivity analyses. Results Upfront proton treatment costs exceeded that of photons [$16,730.37 (3DCRT), $23,893.83 (IMRT), $41,061.80 (protons)]. Based upon expected population pneumonitis and esophagitis rates for each modality, protons would be expected to recover $1,065.62 and $1,139.63 of the cost difference compared to 3DCRT or IMRT. For patients treated with IMRT experiencing grade 4 pneumonitis or grade 4 esophagitis, costs exceeded patients treated with protons without this toxicity. 3DCRT patients with grade 4 esophagitis had higher costs than proton patients without this toxicity. For the risk group analysis, high risk patients (age >65, carboplatin/paclitaxel) benefited more from proton therapy. A biomarker may allow patient selection for proton therapy, although the AUC alone is not sufficient to determine if the biomarker is clinically useful. Conclusions The comparison between proton and photon/X-ray radiation therapy for NSCLC needs to consider both the up-front cost of treatment and the possible long term cost of complications. In our analysis, current costs favor X-ray therapy. However, relatively small reductions in the cost of proton therapy may result in a shift to the preference for proton therapy.

Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase active site

PubMed Central

Sigala, Paul A.; Fafarman, Aaron T.; Schwans, Jason P.; Fried, Stephen D.; Fenn, Timothy D.; Caaveiro, Jose M. M.; Pybus, Brandon; Ringe, Dagmar; Petsko, Gregory A.; Boxer, Steven G.; Herschlag, Daniel

2013-01-01

Hydrogen bond networks are key elements of protein structure and function but have been challenging to study within the complex protein environment. We have carried out in-depth interrogations of the proton transfer equilibrium within a hydrogen bond network formed to bound phenols in the active site of ketosteroid isomerase. We systematically varied the proton affinity of the phenol using differing electron-withdrawing substituents and incorporated site-specific NMR and IR probes to quantitatively map the proton and charge rearrangements within the network that accompany incremental increases in phenol proton affinity. The observed ionization changes were accurately described by a simple equilibrium proton transfer model that strongly suggests the intrinsic proton affinity of one of the Tyr residues in the network, Tyr16, does not remain constant but rather systematically increases due to weakening of the phenol–Tyr16 anion hydrogen bond with increasing phenol proton affinity. Using vibrational Stark spectroscopy, we quantified the electrostatic field changes within the surrounding active site that accompany these rearrangements within the network. We were able to model these changes accurately using continuum electrostatic calculations, suggesting a high degree of conformational restriction within the protein matrix. Our study affords direct insight into the physical and energetic properties of a hydrogen bond network within a protein interior and provides an example of a highly controlled system with minimal conformational rearrangements in which the observed physical changes can be accurately modeled by theoretical calculations. PMID:23798390

Protein conformational modifications and kinetics of water-protein interactions in milk protein concentrate powder upon aging: effect on solubility.

PubMed

Haque, Enamul; Bhandari, Bhesh R; Gidley, Michael J; Deeth, Hilton C; Møller, Sandie M; Whittaker, Andrew K

2010-07-14

Protein conformational modifications and water-protein interactions are two major factors believed to induce instability of protein and eventually affect the solubility of milk protein concentrate (MPC) powder. To test these hypotheses, MPC was stored at different water activities (a(w) 0.0-0.85) and temperatures (25 and 45 degrees C) for up to 12 weeks. Samples were examined periodically to determine solubility, change in protein conformation by Fourier transform infrared (FTIR) spectroscopy and principal component analysis (PCA), and water status (interaction of water with the protein molecule/surface) by measuring the transverse relaxation time (T(2)) with proton nuclear magnetic resonance ((1)H NMR). The solubility of MPC decreased significantly with aging, and this process was enhanced by increasing water activity (a(w)) and storage temperature. Minor changes in protein secondary structure were observed with FTIR, which indicated some degree of unfolding of protein molecules. PCA of the FTIR data was able to discriminate samples according to moisture content and storage period. Partial least-squares (PLS) analysis showed some correlation between FTIR spectral feature and solubility. The NMR T(2) results indicated the presence of three distinct populations of water molecules, and the proton signal intensity and T(2) values of proton fractions varied with storage conditions (humidity, temperature) and aging. Results suggest that protein/protein interactions may be initiated by unfolding of protein molecules that eventually affects solubility.

CMOS Active Pixel Sensors as energy-range detectors for proton Computed Tomography.

PubMed

Esposito, M; Anaxagoras, T; Evans, P M; Green, S; Manolopoulos, S; Nieto-Camero, J; Parker, D J; Poludniowski, G; Price, T; Waltham, C; Allinson, N M

2015-06-03

Since the first proof of concept in the early 70s, a number of technologies has been proposed to perform proton CT (pCT), as a means of mapping tissue stopping power for accurate treatment planning in proton therapy. Previous prototypes of energy-range detectors for pCT have been mainly based on the use of scintillator-based calorimeters, to measure proton residual energy after passing through the patient. However, such an approach is limited by the need for only a single proton passing through the energy-range detector in a read-out cycle. A novel approach to this problem could be the use of pixelated detectors, where the independent read-out of each pixel allows to measure simultaneously the residual energy of a number of protons in the same read-out cycle, facilitating a faster and more efficient pCT scan. This paper investigates the suitability of CMOS Active Pixel Sensors (APSs) to track individual protons as they go through a number of CMOS layers, forming an energy-range telescope. Measurements performed at the iThemba Laboratories will be presented and analysed in terms of correlation, to confirm capability of proton tracking for CMOS APSs.

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.

SU-F-T-154: An Evaluation and Quantification of Secondary Neutron Radiation Dose Due to Double Scatter and Pencil Beam Scanning Proton Therapy

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

Glick, A; Diffenderfer, E

2016-06-15

Proton radiation therapy can deliver high radiation doses to tumors while sparing normal tissue. However, protons yield secondary neutron and gamma radiation that is difficult to detect, small in comparison to the prescribed dose, and not accounted for in most treatment planning systems. The risk for secondary malignancies after proton therapy may be dependent on the quality of this dose. Consequently, there is interest in characterizing the secondary radiation. Previously, we used the dual ionization chamber method to measure the separate absorbed dose from gamma-rays and neutrons secondary to the proton beam1, relying on characterization of ionization chamber response inmore » the unknown neutron spectrum from Monte Carlo simulation. We developed a procedure to use Shieldwerx activation foils, with neutron activation energies ranging from 0.025 eV to 13.5 MeV, to measure the neutron energy spectrum from double scattering (DS) and pencil beam scanning (PBS) protons outside of the treatment volume in a water tank. The activated foils are transferred to a NaI well chamber for gamma-ray spectroscopy and activity measurement. Since PBS treats in layers, the switching time between layers is used to correct for the decay of the activated foils and the relative dose per layer is assumed to be proportional to the neutron fluence per layer. MATLAB code was developed to incorporate the layer delivery and switching time into a calculation of foil activity, which is then used to determine the neutron energy fluence from tabulated foil activation energy thresholds.1. Diffenderfer et. al., Med. Phys., 38(11) 2011.« less

Lysosomal ROS formation.

PubMed

Nohl, Hans; Gille, Lars

2005-01-01

Ubiquinone is inhomogenously distributed in subcellular biomembranes. Apart from mitochondria, where ubiquinone has bioenergetic and pathophysiological functions, unusually high levels of ubiquinone have also been reported in Golgi vesicles and lysosomes. In lysosomes, the interior differs from other organelles in its low pH value which is important to ensure optimal activity of hydrolytic enzymes. Since redox-cycling of ubiquinone is associated with the acceptance and release of protons, we assumed that ubiquinone is part of a redox chain contributing to unilateral proton distribution. A similar function of ubiquinone was earlier suggested by Crane to operate in Golgi vesicles. Support for the involvement of ubiquinone in a presumed couple of redox carriers came from our observation that almost 70% of total lysosomal ubiquinone was in the divalently reduced state. Further reduction was seen in the presence of external NADH. Analysis of the components involved in the transfer of reducing equivalents from cytosolic NADH to ubiquinone revealed the existence of an FAD-containing NADH dehydrogenase. The latter was found to reduce ubiquinone by means of a b-type cytochrome. Proton translocation into the interior was linked to the activity of the novel lysosomal redox chain. Oxygen was found to be the terminal electron acceptor, thereby also regulating acidification of the lysosomal matrix. In contrast to mitochondrial respiration, oxygen was only trivalently reduced giving rise to the release of HO radicals. The role of this novel proton-pumping redox chain and the significance of the associated ROS formation has to be elucidated.

Study of ring influence and electronic response to proton transfer reactions. Reaction electronic flux analysis.

PubMed

Herrera, Barbara

2011-05-01

In this article, a theoretical study of 1-5 proton transfers is presented. Two model systems which represent 1-5 proton transfer, 3-hidroxy-2-propenimine and salicyldenaniline have been studied as shown in Fig. 1. For this purpose, a DFT/B3LYP/6-311+G**, reaction force and reaction electronic flux analysis is made. The obtained results indicate that both proton transfers exhibit energetic and electronic differences emphasizing the role of the neighbor ring and the impact of conjugation on electronic properties.

The kinetic energy spectrum of protons produced by the dissociative ionization of H2 by electron impact

NASA Technical Reports Server (NTRS)

Khakoo, M. A.; Srivastava, S. K.

1985-01-01

The kinetic energy spectra of protons resulting from the dissociative ionization of H2 by electron impact have been measured for electron impact energies from threshold (approximately 17 eV) to 160 eV at 90 deg and 30 deg detection angles, using a crossed-beam experimental arrangement. To check reliability, two separate proton energy analysis methods have been employed, i.e., a time-of-flight proton energy analysis and an electrostatic hemispherical energy analyzer. The present results are compared with previous measurements.

Characterization of proton conducting blend polymer electrolyte using PVA-PAN doped with NH{sub 4}SCN

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

Premalatha, M.; Materials Research Center, Coimbatore-641 045; Mathavan, T., E-mail: tjmathavan@gmail.com, E-mail: kingslin.genova20@gmail.com

2016-05-23

Polymer electrolytes with proton conductivity based on blend polymer using polyvinyl alcohol (PVA) and poly acrylo nitrile (PAN) doped with ammonium thiocyanate have been prepared by solution casting method using DMF as solvent. The complex formation between the blend polymer and the salt has been confirmed by FTIR Spectroscopy. The amorphous nature of the blend polymer electrolytes have been confirmed by XRD analysis. The highest conductivity at 303 K has been found to be 3.25 × 10{sup −3} S cm{sup −1} for 20 mol % NH{sub 4}SCN doped 92.5PVA:7.5PAN system. The increase in conductivity of the doped blend polymer electrolytes with increasingmore » temperature suggests the Arrhenius type thermally activated process. The activation energy is found to be low (0.066 eV) for the highest conductivity sample.« less

Evaluating the quality of NMR structures by local density of protons.

PubMed

Ban, Yih-En Andrew; Rudolph, Johannes; Zhou, Pei; Edelsbrunner, Herbert

2006-03-01

Evaluating the quality of experimentally determined protein structural models is an essential step toward identifying potential errors and guiding further structural refinement. Herein, we report the use of proton local density as a sensitive measure to assess the quality of nuclear magnetic resonance (NMR) structures. Using 256 high-resolution crystal structures with protons added and optimized, we show that the local density of different proton types display distinct distributions. These distributions can be characterized by statistical moments and are used to establish local density Z-scores for evaluating both global and local packing for individual protons. Analysis of 546 crystal structures at various resolutions shows that the local density Z-scores increase as the structural resolution decreases and correlate well with the ClashScore (Word et al. J Mol Biol 1999;285(4):1711-1733) generated by all atom contact analysis. Local density Z-scores for NMR structures exhibit a significantly wider range of values than for X-ray structures and demonstrate a combination of potentially problematic inflation and compression. Water-refined NMR structures show improved packing quality. Our analysis of a high-quality structural ensemble of ubiquitin refined against order parameters shows proton density distributions that correlate nearly perfectly with our standards derived from crystal structures, further validating our approach. We present an automated analysis and visualization tool for proton packing to evaluate the quality of NMR structures. 2005 Wiley-Liss, Inc.

Unveiling N-protonation and anion-binding effects on Fe/N/C-catalysts for O2 reduction in PEM fuel cells

PubMed Central

Herranz, Juan; Jaouen, Frédéric; Lefèvre, Michel; Kramm, Ulrike I.; Proietti, Eric; Dodelet, Jean-Pol; Bogdanoff, Peter; Fiechter, Sebastian; Abs-Wurmbach, Irmgard; Bertrand, Patrick; Arruda, Thomas M.; Mukerjee, Sanjeev

2013-01-01

The high cost of proton-exchange-membrane fuel cells would be considerably reduced if platinumbased catalysts were replaced by iron-based substitutes, which have recently demonstrated comparable activity for oxygen reduction, but whose cause of activity decay in acidic medium has been elusive. Here, we reveal that the activity of Fe/N/C-catalysts prepared through a pyrolysis in NH3 is mostly imparted by acid-resistant FeN4-sites whose turnover frequency for the O2 reduction can be regulated by fine chemical changes of the catalyst surface. We show that surface N-groups protonate at pH 1 and subsequently bind anions. This results in decreased activity for the O2 reduction. The anions can be removed chemically or thermally, which restores the activity of acid-resistant FeN4-sites. These results are interpreted as an increased turnover frequency of FeN4-sites when specific surface N-groups protonate. These unprecedented findings provide new perspective for stabilizing the most active Fe/N/C-catalysts known to date. PMID:24179561

Unveiling N-protonation and anion-binding effects on Fe/N/C-catalysts for O2 reduction in PEM fuel cells.

PubMed

Herranz, Juan; Jaouen, Frédéric; Lefèvre, Michel; Kramm, Ulrike I; Proietti, Eric; Dodelet, Jean-Pol; Bogdanoff, Peter; Fiechter, Sebastian; Abs-Wurmbach, Irmgard; Bertrand, Patrick; Arruda, Thomas M; Mukerjee, Sanjeev

2011-11-18

The high cost of proton-exchange-membrane fuel cells would be considerably reduced if platinumbased catalysts were replaced by iron-based substitutes, which have recently demonstrated comparable activity for oxygen reduction, but whose cause of activity decay in acidic medium has been elusive. Here, we reveal that the activity of Fe/N/C-catalysts prepared through a pyrolysis in NH 3 is mostly imparted by acid-resistant FeN 4 -sites whose turnover frequency for the O 2 reduction can be regulated by fine chemical changes of the catalyst surface. We show that surface N-groups protonate at pH 1 and subsequently bind anions. This results in decreased activity for the O 2 reduction. The anions can be removed chemically or thermally, which restores the activity of acid-resistant FeN 4 -sites. These results are interpreted as an increased turnover frequency of FeN 4 -sites when specific surface N-groups protonate. These unprecedented findings provide new perspective for stabilizing the most active Fe/N/C-catalysts known to date.

The effective temperature of Peptide ions dissociated by sustained off-resonance irradiation collisional activation in fourier transform mass spectrometry.

PubMed

Schnier, P D; Jurchen, J C; Williams, E R

1999-01-28

A method for determining the internal energy of biomolecule ions activated by collisions is demonstrated. The dissociation kinetics of protonated leucine enkephalin and doubly protonated bradykinin were measured using sustained off-resonance irradiation (SORI) collisionally activated dissociation (CAD) in a Fourier transform mass spectrometer. Dissociation rate constants are obtained from these kinetic data. In combination with Arrhenius parameters measured with blackbody infrared radiative dissociation, the "effective" temperatures of these ions are obtained. Effects of excitation voltage and frequency and the ion cell pressure were investigated. With typical SORI-CAD experimental conditions, the effective temperatures of these peptide ions range between 200 and 400 degrees C. Higher temperatures can be easily obtained for ions that require more internal energy to dissociate. The effective temperatures of both protonated leucine enkephalin and doubly protonated bradykinin measured with the same experimental conditions are similar. Effective temperatures for protonated leucine enkephalin can also be obtained from the branching ratio of the b(4) and (M + H - H(2)O)(+) pathways. Values obtained from this method are in good agreement with those obtained from the overall dissociation rate constants. Protonated leucine enkephalin is an excellent "thermometer" ion and should be well suited to establishing effective temperatures of ions activated by other dissociation techniques, such as infrared photodissociation, as well as ionization methods, such as matrix assisted laser desorption/ionization.

The Effective Temperature of Peptide Ions Dissociated by Sustained Off-Resonance Irradiation Collisional Activation in Fourier Transform Mass Spectrometry

PubMed Central

Schnier, Paul D.; Jurchen, John C.; Williams, Evan R.

2005-01-01

A method for determining the internal energy of biomolecule ions activated by collisions is demonstrated. The dissociation kinetics of protonated leucine enkephalin and doubly protonated bradykinin were measured using sustained off-resonance irradiation (SORI) collisionally activated dissociation (CAD) in a Fourier transform mass spectrometer. Dissociation rate constants are obtained from these kinetic data. In combination with Arrhenius parameters measured with blackbody infrared radiative dissociation, the “effective” temperatures of these ions are obtained. Effects of excitation voltage and frequency and the ion cell pressure were investigated. With typical SORI–CAD experimental conditions, the effective temperatures of these peptide ions range between 200 and 400 °C. Higher temperatures can be easily obtained for ions that require more internal energy to dissociate. The effective temperatures of both protonated leucine enkephalin and doubly protonated bradykinin measured with the same experimental conditions are similar. Effective temperatures for protonated leucine enkephalin can also be obtained from the branching ratio of the b4 and (M + H − H2O)+ pathways. Values obtained from this method are in good agreement with those obtained from the overall dissociation rate constants. Protonated leucine enkephalin is an excellent “thermometer” ion and should be well suited to establishing effective temperatures of ions activated by other dissociation techniques, such as infrared photodissociation, as well as ionization methods, such as matrix assisted laser desorption/ionization. PMID:16614752

Proton channel HVCN1 is required for effector functions of mouse eosinophils

PubMed Central

2013-01-01

Background Proton currents are required for optimal respiratory burst in phagocytes. Recently, HVCN1 was identified as the molecule required for the voltage-gated proton channel activity associated with the respiratory burst in neutrophils. Although there are similarities between eosinophils and neutrophils regarding their mechanism for respiratory burst, the role of proton channels in eosinophil functions has not been fully understood. Results In the present study, we first identified the expression of the proton channel HVCN1 in mouse eosinophils. Furthermore, using HVCN1-deficient eosinophils, we demonstrated important cell-specific effector functions for HVCN1. Similar to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils produced significantly less reactive oxygen species (ROS) upon phorbol myristate acetate (PMA) stimulation compared with WT eosinophils. In contrast to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils did not show impaired calcium mobilization or migration ability compared with wild-type (WT) cells. Uniquely, HVCN1-deficient eosinophils underwent significantly increased cell death induced by PMA stimulation compared with WT eosinophils. The increased cell death was dependent on NADPH oxidase activation, and correlated with the failure of HVCN1-deficient cells to maintain membrane polarization and intracellular pH in the physiological range upon activation. Conclusions Eosinophils require proton channel HVCN1 for optimal ROS generation and prevention of activation-induced cell death. PMID:23705768

Selective production of sealed plasma membrane vesicles from red beet (Beta vulgaris L.) storage tissue.

PubMed

Giannini, J L; Gildensoph, L H; Briskin, D P

1987-05-01

Modification of our previous procedure for the isolation of microsomal membrane vesicles from red beet (Beta vulgaris L.) storage tissue allowed the recovery of sealed membrane vesicles displaying proton transport activity sensitive to both nitrate and orthovanadate. In the absence of a high salt concentration in the homogenization medium, contributions of nitrate-sensitive (tonoplast) and vanadate-sensitive (plasma membrane) proton transport were roughly equal. The addition of 0.25 M KCl to the homogenization medium increased the relative amount of nitrate-inhibited proton transport activity while the addition of 0.25 M KI resulted in proton pumping vesicles displaying inhibition by vanadate but stimulation by nitrate. These effects appeared to result from selective sealing of either plasma membrane or tonoplast membrane vesicles during homogenization in the presence of the two salts. Following centrifugation on linear sucrose gradients it was shown that the nitrate-sensitive, proton-transporting vesicles banded at low density and comigrated with nitrate-sensitive ATPase activity while the vanadate-sensitive, proton-transporting vesicles banded at a much higher density and comigrated with vanadate-sensitive ATPase. The properties of the vanadate-sensitive proton pumping vesicles were further characterized in microsomal membrane fractions produced by homogenization in the presence of 0.25 M KI and centrifugation on discontinuous sucrose density gradients. Proton transport was substrate specific for ATP, displayed a sharp pH optimum at 6.5, and was insensitive to azide but inhibited by N'-N-dicyclohexylcarbodiimide, diethylstilbestrol, and fluoride. The Km of proton transport for Mg:ATP was 0.67 mM and the K0.5 for vanadate inhibition was at about 50 microM. These properties are identical to those displayed by the plasma membrane ATPase and confirm a plasma membrane origin for the vesicles.

⁵¹V NMR Crystallography of Vanadium Chloroperoxidase and Its Directed Evolution P395D/L241V/T343A Mutant: Protonation Environments of the Active Site.

PubMed

Gupta, Rupal; Hou, Guangjin; Renirie, Rokus; Wever, Ron; Polenova, Tatyana

2015-04-29

Vanadium-dependent haloperoxidases (VHPOs) perform two-electron oxidation of halides using hydrogen peroxide. Their mechanism, including the factors determining the substrate specificity and the pH-dependence of the catalytic rates, is poorly understood. The vanadate cofactor in the active site of VHPOs contains "spectroscopically silent" V(V), which does not change oxidation state during the reaction. We employed an NMR crystallography approach based on (51)V magic angle spinning NMR spectroscopy and Density Functional Theory, to gain insights into the structure and coordination environment of the cofactor in the resting state of vanadium-dependent chloroperoxidases (VCPO). The cofactor environments in the wild-type VCPO and its P395D/L241V/T343A mutant exhibiting 5-100-fold improved catalytic activity are examined at various pH values. Optimal sensitivity attained due to the fast MAS probe technologies enabled the assignment of the location and number of protons on the vanadate as a function of pH. The vanadate cofactor changes its protonation from quadruply protonated at pH 6.3 to triply protonated at pH 7.3 to doubly protonated at pH 8.3. In contrast, in the mutant, the vanadate protonation is the same at pH 5.0 and 8.3, and the cofactor is doubly protonated. This methodology to identify the distinct protonation environments of the cofactor, which are also pH-dependent, could help explain the different reactivities of the wild-type and mutant VCPO and their pH-dependence. This study demonstrates that (51)V-based NMR crystallography can be used to derive the detailed coordination environments of vanadium centers in large biological molecules.

Nickel-Catalyzed Proton-Deuterium Exchange (HDX) Procedures for Glycosidic Linkage Analysis of Complex Carbohydrates.

PubMed

Price, Neil P J; Hartman, Trina M; Vermillion, Karl E

2015-07-21

The structural analysis of complex carbohydrates typically requires the assignment of three parameters: monosaccharide composition, the position of glycosidic linkages between monosaccharides, and the position and nature of noncarbohydrate substituents. The glycosidic linkage positions are often determined by permethylation analysis, but this can be complicated by high viscosity or poor solubility, resulting in under-methylation. This is a drawback because an under-methylated position may be misinterpreted as the erroneous site of a linkage or substituent. Here, we describe an alternative approach to linkage analysis that makes use of a nonreversible deuterium exchange of C-H protons on the carbohydrate backbone. The exchange reaction is conducted in deuterated water catalyzed by Raney nickel, and results in the selective exchange of C-H protons adjacent to free hydroxyl groups. Hence, the position of the residual C-H protons is indicative of the position of glycosidic linkages or other substituents and can be readily assigned by heteronuclear single quantum coherence-nuclear magnetic resonance (HSQC-NMR) or, following suitable derivatization, by gas chromatography-mass spectroscopy (GC/MS) analysis. Moreover, because the only changes to the parent sugar are proton/deuterium exchanges, the composition and linkage analysis can be determined in a single step.

Proton-proton bremsstrahlung towards the elastic limit

NASA Astrophysics Data System (ADS)

Mahjour-Shafiei, M.; Amir-Ahmadi, H. R.; Bacelar, J. C. S.; Castelijns, R.; Ermisch, K.; van Garderen, E.; Gašparić, I.; Harakeh, M. N.; Kalantar-Nayestanaki, N.; Kiš, M.; Löhner, H.

2005-05-01

In oder to study proton-proton bremsstrahlung moving towards the elastic limit, a detection system, consisting of Plastic-ball and SALAD, was set up and an experiment at 190 MeV incident beam energy was performed. Here, the experimental setup and the data analysis procedure along with some results obtained in the measurement are discussed.

Comparative analysis of proton- and neutron-halo breakups

NASA Astrophysics Data System (ADS)

Mukeru, B.

2018-06-01

A detailed analysis of the proton- and neutron-halo breakup cross sections is presented. Larger neutron-halo breakup cross sections than proton-halo breakup cross sections are obtained. This is found to be mainly due to the projectile structure, namely the ground state wave function and the dipole electric response function. It is also found that the continuum–continuum couplings are stronger in the proton-halo breakup than in the neutron-halo breakup. The increase of proton- and neutron-halo ground state separation energy slightly strengthens these couplings in the proton- and neutron-halo total and nuclear breakups, while they are weakened in the proton- and neutron-halo Coulomb breakups. The Coulomb-nuclear interference remains strongly destructive in both proton- and neutron-halo breakups and this is independent of the ground state separation energy. The results also show that the increase of the neutron-halo ground state separation energy decreases significantly the agreement between the proton- and neutron-halo breakup cross sections, both qualitatively and quantitatively. It is obtained that when the proton-halo ground state separation energy is increased by a factor of 4.380, the proton-halo breakup cross section is reduced by a factor of 4.392, indicating a clear proportionality. However, when the neutron-halo ground state separation energy is increased by the same factor, the neutron-halo total breakup cross section is reduced by a factor of 8.522.

On the change in the spectral composition of solar ultraviolet emission preceding proton flares, and its connection with the preflare fluctuations in the horizontal component of the geomagnetic field

NASA Astrophysics Data System (ADS)

Sheiner, Olga; Snegirev, Sergei; Smirnova, Anna

The importance problem of Solar-terrestrial physics is regular forecasting of solar activity phenomena, which negatively influence the human’s health, operating safety, communication, radar sets and others. We previously reported the existence of long-period pulsations of H component of the geomagnetic field recorded at stations tested 2-3 days before the proton solar flares. There are the increasing of pulsation amplitude of the horizontal component of the magnetic field with periods of 30-60 minutes. The spectrum of the flux of ultraviolet solar radiation on the eve of proton flares was conducted to determine the presence of oscillations - precursors of flares, as one of the possible agents causing amplification of large periods pulsations of H component of the geomagnetic field. Used data on ultraviolet radiation of the sun with a wavelength of 115-127 nm are obtained from a geostationary satellite GOES 15, the method of wavelet analysis is used. It is found the congruence in the behavior of spectral components with periods of 30-60 minutes in the ground-based measurements and in UV emission for 3-1 days before the proton flare.

Fast method for in-flight estimation of total dose from protons and electrons using RADE Minstrument on JUICE

NASA Astrophysics Data System (ADS)

Hajdas, Wojtek; Mrigakshi, Alankrita; Xiao, Hualin

2017-04-01

The primary concern of the ESA JUICE mission to Jupiter is the harsh particle radiation environment. Ionizing particles introduce radiation damage by total dose effects, displacement damages or single events effects. Therefore, both the total ionizing dose and the displacement damage equivalent fluence must be assessed to alert spacecraft and its payload as well as to quantify radiation levels for the entire mission lifetime. We present a concept and implementations steps for simplified method used to compute in flight a dose rate and total dose caused by protons. We also provide refinement of the method previously developed for electrons. The dose rates values are given for predefined active volumes located behind layers of materials with known thickness. Both methods are based on the electron and proton flux measurements provided by the Electron and Proton Detectors inside the Radiation Hard Electron Monitor (RADEM) located on-board of JUICE. The trade-off between method accuracy and programming limitations for in-flight computations are discussed. More comprehensive and precise dose rate computations based on detailed analysis of all stack detectors will be made during off-line data processing. It will utilize full spectral unfolding from all RADEM detector subsystems.

Muon motion in titanium hydride

NASA Technical Reports Server (NTRS)

Kempton, J. R.; Petzinger, K. G.; Kossler, W. J.; Schone, H. E.; Hitti, B. S.; Stronach, C. E.; Adu, N.; Lankford, W. F.; Reilly, J. J.; Seymour, E. F. W.

1988-01-01

Motional narrowing of the transverse-field muon spin rotation signal was observed in gamma-TiH(x) for x = 1.83, 1.97, and 1.99. An analysis of the data for TiH1.99 near room temperature indicates that the mechanism responsible for the motion of the muon out of the octahedral site is thermally activated diffusion with an attempt frequency comparable to the optical vibrations of the lattice. Monte Carlo calculations to simulate the effect of muon and proton motion upon the muon field-correlation time were used to interpret the motional narrowing in TiH1.97 near 500 K. The interpretation is dependent upon whether the Bloembergen, Purcell, and Pound (BPP) theory or an independent spin-pair relaxation model is used to obtain the vacancy jump rate from proton NMR T1 measurements. Use of BPP theory shows that the field-correction time can be obtained if the rate of motion of the muon with respect to the rate of the motion for the protons is decreased. An independent spin-pair relaxation model indicates that the field-correlation time can be obtained if the rate of motion for the nearest-neighbor protons is decreased.

1H NMR study of the effect of heme insertion on the folding of apomyoglobin

NASA Astrophysics Data System (ADS)

Yamamoto, Yasuhiko; Takemoto, Kenji; Matsuo, Hitomi

2002-01-01

NMR signals arising from His EF5 and His GH1 N ɛH protons of sperm whale myoglobin and apomyoglobin have been assigned, and the protein folding has been studied through the analysis of these signals. His EF5 and His GH1 N ɛH protons participate in the internal hydrogen bonds at the B-GH and EF-H interfaces, respectively, and their signals are remarkably sensitive to local structural alterations at these sites. The shifts of these signals in alkaline pH condition were only slightly affected by the removal of heme, indicating that the overall protein folding is essentially retained in apoprotein. The line width of His EF5 proton signal, however, increased largely in the spectra of apomyoglobin and this result suggests a conformational lability of the EF-H interface in the absence of heme. Furthermore, the His EF5 proton signal was found to be influenced by not only the orientation of heme relative to the protein, but also by the type of hemin used to reconstitute apomyoglobin. These results clearly demonstrate the presence of a long-range structural correlation between the heme active site and the EF-H interface.

An integrated field-effect microdevice for monitoring membrane transport in Xenopus laevis oocytes via lateral proton diffusion.

PubMed

Schaffhauser, Daniel Felix; Patti, Monica; Goda, Tatsuro; Miyahara, Yuji; Forster, Ian Cameron; Dittrich, Petra Stephanie

2012-01-01

An integrated microdevice for measuring proton-dependent membrane activity at the surface of Xenopus laevis oocytes is presented. By establishing a stable contact between the oocyte vitelline membrane and an ion-sensitive field-effect (ISFET) sensor inside a microperfusion channel, changes in surface pH that are hypothesized to result from facilitated proton lateral diffusion along the membrane were detected. The solute diffusion barrier created between the sensor and the active membrane area allowed detection of surface proton concentration free from interference of solutes in bulk solution. The proposed sensor mechanism was verified by heterologously expressing membrane transport proteins and recording changes in surface pH during application of the specific substrates. Experiments conducted on two families of phosphate-sodium cotransporters (SLC20 & SLC34) demonstrated that it is possible to detect phosphate transport for both electrogenic and electroneutral isoforms and distinguish between transport of different phosphate species. Furthermore, the transport activity of the proton/amino acid cotransporter PAT1 assayed using conventional whole cell electrophysiology correlated well with changes in surface pH, confirming the ability of the system to detect activity proportional to expression level.

Solar flares, proton showers, and the Space Shuttle

NASA Technical Reports Server (NTRS)

Rust, D. M.

1982-01-01

Attention is given the hazards posed to Space Shuttle crews by energetic proton radiation from inherently unpredictable solar flares, such as that of April 10-13, 1981, which was experienced by the Space Shuttle Columbia. The most energetic protons from this flare reached the earth's atmosphere an hour after flare onset, and would have posed a potentially lethal threat to astronauts engaged in extravehicular activity in a polar or geosynchronous orbit rather than the low-latitude, low-altitude orbit of this mission. It is shown that proton-producing flares are associated with energization in shocks, many of which are driven by coronal mass ejections. Insights gained from the Solar Maximum Year programs allow reconsideration of proton shower forecasting, which will be essential in the prediction of the weather that Space Shuttle astronauts will encounter during extravehicular activities.

Measurement of excitation functions and analysis of isomeric population in some reactions induced by proton on natural indium at low energy

NASA Astrophysics Data System (ADS)

Muhammed Shan, P. T.; Musthafa, M. M.; Najmunnisa, T.; Mohamed Aslam, P.; Rajesh, K. K.; Hajara, K.; Surendran, P.; Nair, J. P.; Shanbagh, Anil; Ghugre, S.

2018-06-01

The excitation functions for reaction residues populated via 115In(p , p) 115 mIn, 115In(p , pn) 114 mIn, 115In(p , p 2 n) 113 mIn, 113In(p , p) 113 mIn, 115In(p , nα) 111 mCd, 115In(p , 3 n) 113Sn and 113In(p , n) 113Sn channels were measured over the proton energy range of 8-22 MeV using stacked foil activation technique. Theoretical analysis of the data were performed within the framework of two statistical model codes EMPIRE-3.2 and TALYS-1.8. Isomeric cross section ratio for isomeric pairs m,g 115In, m,g 114In, m,g 113In, 113Sn m,g and m,g 111Cd were determined for the first time. The dependence of isomeric cross section ratio on various factors are analysed.

Proton transport behavior through the influenza A M2 channel: insights from molecular simulation.

PubMed

Chen, Hanning; Wu, Yujie; Voth, Gregory A

2007-11-15

The structural properties of the influenza A virus M2 transmembrane channel in dimyristoylphosphatidylcholine bilayer for each of the four protonation states of the proton-gating His-37 tetrad and their effects on proton transport for this low-pH activated, highly proton-selective channel are studied by classical molecular dynamics with the multistate empirical valence-bond (MS-EVB) methodology. The excess proton permeation free energy profile and maximum ion conductance calculated from the MS-EVB simulation data combined with the Poisson-Nernst-Planck theory indicates that the triply protonated His-37 state is the most likely open state via a significant side-chain conformational change of the His-37 tetrad. This proposed open state of M2 has a calculated proton permeation free energy barrier of 7 kcal/mol and a maximum conductance of 53 pS compared to the experimental value of 6 pS. By contrast, the maximum conductance for Na(+) is calculated to be four orders of magnitude lower, in reasonable agreement with the experimentally observed proton selectivity. The pH value to activate the channel opening is estimated to be 5.5 from dielectric continuum theory, which is also consistent with experimental results. This study further reveals that the Ala-29 residue region is the primary binding site for the antiflu drug amantadine (AMT), probably because that domain is relatively spacious and hydrophobic. The presence of AMT is calculated to reduce the proton conductance by 99.8% due to a significant dehydration penalty of the excess proton in the vicinity of the channel-bound AMT.

Proton transfer in organic scaffolds

NASA Astrophysics Data System (ADS)

Basak, Dipankar

This dissertation focuses on the fundamental understanding of the proton transfer process and translating the knowledge into design/development of new organic materials for efficient non-aqueous proton transport. For example, what controls the shuttling of a proton between two basic sites? a) Distance between two groups? or b) the basicity? c) What is the impact of protonation on molecular conformation when the basic sites are attached to rigid scaffolds? For this purpose, we developed several tunable proton sponges and studied proton transfer in these scaffolds theoretically as well as experimentally. Next we moved our attention to understand long-range proton conduction or proton transport. We introduced liquid crystalline (LC) proton conductor based on triphenylene molecule and established that activation energy barrier for proton transport is lower in the LC phase compared to the crystalline phase. Furthermore, we investigated the impact of several critical factors: the choice of the proton transferring groups, mobility of the charge carriers, intrinsic vs. extrinsic charge carrier concentrations and the molecular architectures on long-range proton transport. The outcome of this research will lead to a deeper understanding of non-aqueous proton transfer process and aid the design of next generation proton exchange membrane (PEM) for fuel cell.

Experimental and Theoretical Studies on Gas-Phase Fragmentation Reactions of Protonated Methyl Benzoate: Concomitant Neutral Eliminations of Benzene, Carbon Dioxide, and Methanol

NASA Astrophysics Data System (ADS)

Xia, Hanxue; Zhang, Yong; Attygalle, Athula B.

2018-06-01

Protonated methyl benzoate, upon activation, fragments by three distinct pathways. The m/z 137 ion for the protonated species generated by helium-plasma ionization (HePI) was mass-selected and subjected to collisional activation. In one fragmentation pathway, the protonated molecule generated a product ion of m/z 59 by eliminating a molecule of benzene (Pathway I). The m/z 59 ion (generally recognized as the methoxycarbonyl cation) produced in this way, then formed a methyl carbenium ion in situ by decarboxylation, which in turn evoked an electrophilic aromatic addition reaction on the benzene ring by a termolecular process to generate the toluenium cation (Pathway II). Moreover, protonated methyl benzoate undergoes also a methanol loss (Pathway III). However, it is not a simple removal of a methanol molecule after a protonation on the methoxy group. The incipient proton migrates to the ring and randomizes to a certain degree before a subsequent transfer of one of the ring protons to the alkoxy group for the concomitant methanol elimination. The spectrum recorded from deuteronated methyl benzoate showed two peaks at m/z 105 and 106 for the benzoyl cation at a ratio of 2:1, confirming the charge-imparting proton is mobile. However, the proton transfer from the benzenium intermediate to the methoxy group for the methanol loss occurs before achieving a complete state of scrambling. [Figure not available: see fulltext.

Molecular Dynamics Study of the Proposed Proton Transport Pathways in [FeFe]-Hydrogenase

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

Ginovska-Pangovska, Bojana; Ho, Ming-Hsun; Linehan, John C.

2014-01-15

Possible proton channels in Clostridium pasteurianum [FeFe]-hydrogenase were investigated with molecular dynamics simulations. This study was undertaken to discern proposed channels, compare their properties, evaluate the functional channel, and to provide insight into the features of an active proton channel. Our simulations suggest that protons are not transported through water wires. Instead, a five-residue motif (E282, S319, E279, HOH, C299) was found to be the likely channel, consistent with experimental observations. This channel connects the surface of the enzyme and the di-thiomethylamine bridge of the catalytic H-cluster, permitting the transport of protons. The channel was found to have a persistentmore » hydrogen bonded core (residues E279 to S319), with less persistent hydrogen bonds at the ends of the channel. The hydrogen bond occupancy in this network was found to be sensitive to the protonation state of the residues in the channel, with different protonation states enhancing or stabilizing hydrogen bonding in different regions of the network. Single site mutations to non-hydrogen bonding residues break the hydrogen bonding network at that residue, consistent with experimental observations showing catalyst inactivation. In many cases, these mutations alter the hydrogen bonding in other regions of the channel which may be equally important in catalytic failure. A correlation between the protein dynamics near the proton channel and the redox partner binding regions was also found as a function of protonation state. The likely mechanism of proton movement in [FeFe]-hydrogenases is discussed based on the structural analysis presented here. This work was funded by the DOE Office of Science Early Career Research Program through the Office of Basic Energy Sciences. Computational resources were provided at W. R. Wiley Environmental Molecular Science Laboratory (EMSL), a national scientific user facility sponsored by the Department of Energy’s Office of Biological and Environmental Research located at Pacific Northwest National Laboratory, and a portion of the research was performed using PNNL Institutional Computing at Pacific Northwest National Laboratory. Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.« less

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.

Structural mechanism of enoyl-CoA hydratase: three atoms from a single water are added in either an E1cb stepwise or concerted fashion.

PubMed

Bahnson, Brian J; Anderson, Vernon E; Petsko, Gregory A

2002-02-26

We have determined the crystal structure of the enzyme enoyl-CoA hydratase (ECH) from rat liver with the bound substrate 4-(N,N-dimethylamino)cinnamoyl-CoA using X-ray diffraction data to a resolution of 2.3 A. In addition to the thiolester substrate, the catalytic water, which is added in the hydration reaction, has been modeled into well-defined electron density in each of the six active sites of the physiological hexamer within the crystallographic asymmetric unit. The catalytic water bridges Glu(144) and Glu(164) of the enzyme and has a lone pair of electrons poised to react with C(3) of the enzyme-bound alpha,beta-unsaturated thiolester. The water molecule, which bridges two glutamate residues, is reminiscent of the enolase active site. However, unlike enolase, which has a lysine available to donate a proton, there are no other sources of protons available from other active site residues in ECH. Furthermore, an analysis of the hydrogen-bonding network of the active site suggests that both Glu(144) and Glu(164) are ionized and carry a negative charge with no reasonable place to have a protonated carboxylate. This lack of hydrogen-bonding acceptors that could accommodate a source of a proton, other than from the water molecule, leads to a hypothesis that the three atoms from a single water molecule are added across the double bond to form the hydrated product. The structural results are discussed in connection with details of the mechanism, which have been elucidated from kinetics, site-directed mutagenesis, and spectroscopy of enzyme-substrate species, in presenting an atomic-resolution mechanism of the reaction. Contrary to the previous interpretation, the structure of the E-S complex together with previously determined kinetic isotope effects is consistent with either a concerted mechanism or an E1cb stepwise mechanism.

Radioprotective effects of delphinidin on normal human lung cells against proton beam exposure

PubMed Central

Kim, Hyun Mi; Kim, Suk Hee

2018-01-01

BACKGROUND/OBJECTIVES Exposure of the normal lung tissue around the cancerous tumor during radiotherapy causes serious side effects such as pneumonitis and pulmonary fibrosis. Radioprotectors used during cancer radiotherapy could protect the patient from side effects induced by radiation injury of the normal tissue. Delphinidin has strong antioxidant properties, and it works as the driving force of a radioprotective effect by scavenging radiation-induced reactive oxygen species (ROS). However, no studies have been conducted on the radioprotective effect of delphinidin against high linear energy transfer radiation. Therefore, this study was undertaken to evaluate the radioprotective effects of delphinidin on human lung cells against a proton beam. MATERIALS/METHODS Normal human lung cells (HEL 299 cells) were used for in vitro experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay assessed the cytotoxicity of delphinidin and cell viability. The expression of radiation induced cellular ROS was measured by the 2′-7′-dicholordihydrofluorescein diacetate assay. Superoxide dismutase activity assay and catalase activity assay were used for evaluating the activity of corresponding enzymes. In addition, radioprotective effects on DNA damage-induced cellular apoptosis were evaluated by Western blot assay. RESULTS Experimental analysis, including cell survival assay, MTT assay, and Western blot assay, revealed the radioprotective effects of delphinidin. These include restoring the activities of antioxidant enzymes of damaged cells, increase in the levels of pro-survival protein, and decrease of pro-apoptosis proteins. The results from different experiments were compatible with each to provide a substantial conclusion. CONCLUSION Low concentration (2.5 µM/mL) of delphinidin administration prior to radiation exposure was radioprotective against a low dose of proton beam exposure. Hence, delphinidin is a promising shielding agent against radiation, protecting the normal tissues around a cancerous tumor, which are unintentionally exposed to low doses of radiation during proton therapy. PMID:29399295

Blackbody Infrared Radiative Dissociation of Bradykinin and Its Analogues: Energetics, Dynamics, and Evidence for Salt-Bridge Structures in the Gas Phase

PubMed Central

Schnier, Paul D.; Price, William D.; Jockusch, Rebecca A.

2005-01-01

Blackbody infrared radiative dissociation (BIRD) spectra of singly and doubly protonated bradykinin and its analogues are measured in a Fourier-transform mass spectrometer. Rate constants for dissociation are measured as a function of temperature with reaction delays up to 600 s. From these data, Arrhenius activation parameters in the zero-pressure limit are obtained. The activation parameters and dissociation products for the singly protonated ions are highly sensitive to small changes in ion structure. The Arrhenius activation energy (Ea) and pre-exponential (or frequency factor, A) of the singly protonated ions investigated here range from 0.6 to 1.4 eV and 105 to 1012 s−1, respectively. For bradykinin and its analogues differing by modification of the residues between the two arginine groups on either end of the molecule, the singly and doubly protonated ions have average activation energies of 1.2 and 0.8 eV, respectively, and average A values of 108 and 1012 s−1, respectively, i.e., the presence of a second charge reduces the activation energy by 0.4 eV and decreases the A value by a factor of 104. This demonstrates that the presence of a second charge can dramatically influence the dissociation dynamics of these ions. The doubly protonated methyl ester of bradykinin has an Ea of 0.82 eV, comparable to the value of 0.84 eV for bradykinin itself. However, this value is 0.21 ± 0.08 eV greater than that of singly protonated methyl ester of bradykinin, indicating that the Coulomb repulsion is not the most significant factor in the activation energy of this ion. Both singly and doubly protonated Lys-bradykinin ions have higher activation energies than the corresponding bradykinin ions indicating that the addition of a basic residue stabilizes these ions with respect to dissociation. Methylation of the carboxylic acid group of the C-terminus reduces the Ea of bradykinin from 1.3 to 0.6 eV and the A factor from 1012 to 105 s−1. This modification also dramatically changes the dissociation products. Similar results are observed for [Ala6]-bradykinin and its methyl ester. These results, in combination with others presented here, provide experimental evidence that the most stable form of singly protonated bradykinin is a salt-bridge structure. PMID:16525512

The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center.

PubMed

Chung, Kwangzoo; Han, Youngyih; Kim, Jinsung; Ahn, Sung Hwan; Ju, Sang Gyu; Jung, Sang Hoon; Chung, Yoonsun; Cho, Sungkoo; Jo, Kwanghyun; Shin, Eun Hyuk; Hong, Chae-Seon; Shin, Jung Suk; Park, Seyjoon; Kim, Dae-Hyun; Kim, Hye Young; Lee, Boram; Shibagaki, Gantaro; Nonaka, Hideki; Sasai, Kenzo; Koyabu, Yukio; Choi, Changhoon; Huh, Seung Jae; Ahn, Yong Chan; Pyo, Hong Ryull; Lim, Do Hoon; Park, Hee Chul; Park, Won; Oh, Dong Ryul; Noh, Jae Myung; Yu, Jeong Il; Song, Sanghyuk; Lee, Ji Eun; Lee, Bomi; Choi, Doo Ho

2015-12-01

The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.

Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose–volume histogram analysis

PubMed Central

Makishima, Hirokazu; Ishikawa, Hitoshi; Terunuma, Toshiyuki; Hashimoto, Takayuki; Yamanashi, Koichi; Sekiguchi, Takao; Mizumoto, Masashi; Okumura, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

2015-01-01

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose–volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5–V20, mean lung dose (MLD), and heart V30–V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer. PMID:25755255

Effects of Proton and Combined Proton and (56)Fe Radiation on the Hippocampus.

PubMed

Raber, Jacob; Allen, Antiño R; Sharma, Sourabh; Allen, Barrett; Rosi, Susanna; Olsen, Reid H J; Davis, Matthew J; Eiwaz, Massarra; Fike, John R; Nelson, Gregory A

2016-01-01

The space radiation environment contains protons and (56)Fe, which could pose a significant hazard to space flight crews during and after missions. The space environment involves complex radiation exposures, thus, the effects of a dose of protons might be modulated by a dose of heavy-ion radiation. The brain, and particularly the hippocampus, may be susceptible to space radiation-induced changes. In this study, we first determined the dose-response effect of proton radiation (150 MeV) on hippocampus-dependent cognition 1 and 3 months after exposure. Based on those results, we subsequently exposed mice to protons alone (150 MeV, 0.1 Gy), (56)Fe alone (600 MeV/n, 0.5 Gy) or combined proton and (56)Fe radiations (protons first) with the two exposures separated by 24 h. At one month postirradiation, all animal groups showed novel object recognition. However, at three months postirradiation, mice exposed to either protons or combined proton and (56)Fe radiations showed impaired novel object recognition, which was not observed in mice irradiated with (56)Fe alone. The mechanisms in these impairments might involve inflammation. In mice irradiated with protons alone or (56)Fe alone three months earlier, there was a negative correlation between a measure of novel object recognition and the number of newly born activated microglia in the dentate gyrus. Next, cytokine and chemokine levels were assessed in the hippocampus. At one month after exposure the levels of IL-12 were higher in mice exposed to combined radiations compared with sham-irradiated mice, while the levels of IFN-γ were lower in mice exposed to (56)Fe radiation alone or combined radiations. In addition, IL-4 levels were lower in (56)Fe-irradiated mice compared with proton-irradiated mice and TNF-α levels were lower in proton-irradiated mice than in mice receiving combined radiations. At three months after exposure, macrophage-derived chemokine (MDC) and eotaxin levels were lower in mice receiving combined radiations. The levels of MDC and eotaxin correlated and the levels of MDC, but not eotaxin, correlated with the percentage of newly born activated microglia in the blades of the dentate gyrus. Finally, hippocampal IL-6 levels were higher in mice receiving combined radiations compared with mice receiving (56)Fe radiation alone. These data demonstrate the sensitivity of novel object recognition for detecting cognitive injury three months after exposure to proton radiation alone, and combined exposure to proton and (56)Fe radiations, and that newly-born activated microglia and inflammation might be involved in this injury.

Radioactivity observed in scintillation counters during the HEAO-1 mission

NASA Technical Reports Server (NTRS)

Gruber, D. E.; Jung, G. V.; Matteson, J. L.

1989-01-01

Results are reported from an analysis of radioactivity induced in the NaI medium-energy detector of the hard X-ray and low-energy gamma-ray experiment during the HEAO-1 satellite mission (1977-1978). Consideration is given to the instrument characteristics, the origin and variability of background, and the separation of cosmic-ray activity from the internal activity due to South Atlantic Anomaly trapped protons. Energy spectra and tables listing the nuclide identifications are provided.

Dosimetric and clinical experience in eye proton treatment at INFN-LNS

NASA Astrophysics Data System (ADS)

Cirrone, G. A. P.; Cuttone, G.; Di Rosa, F.; Lojacono, P.; Mongelli, V.; Lo Nigro, S.; Ott, J.; Patti, I. V.; Pittera, S.; Privitera, G.; Raffaele, L.; Reibaldi, A.; Russo, G.; Salamone, V.; Sabini, M. G.; Spatola, C.; Valastro, L. M.

2009-05-01

After six years of activity 155 patients have been treated inside the CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) facility. CATANA is the first and unique proton therapy facility in which the 62 MeV proton beams, accelerated by a Superconducting Cyclotron, are used for the radio-therapeutic treatments of choroidal and iris melanomas. Inside CATANA new absolute and relative dosimetric techniques have been developed in order to achieve the best results in terms of treatment precision and dose release accuracy. The follow-up results for 42 patients demonstrated the efficacy of high energy protons in the radiotherapeutic field and encouraged us in our activity in the battle against cancer

Why Is It so? The [superscript 1]H-NMR CH[subscript 2] Splitting in Substituted Propanes

ERIC Educational Resources Information Center

Lim, Kieran F.; Dereani, Marino

2010-01-01

Nuclear magnetic resonance (NMR) spectroscopy is an important tool in the structural analysis of both organic and inorganic molecules. Proton NMR spectra can yield information about the chemical or bonding environment surrounding various protons, the number of protons in those environments, and the number of neighbouring protons around each…

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

Sun, Z. J.; Wells, D.; Green, J.

Photon Activation Analysis (PAA) of environmental, archaeological and industrial samples requires extensive data analysis that is susceptible to error. For the purpose of saving time, manpower and minimizing error, a computer program was designed, built and implemented using SQL, Access 2007 and asp.net technology to automate this process. Based on the peak information of the spectrum and assisted by its PAA library, the program automatically identifies elements in the samples and calculates their concentrations and respective uncertainties. The software also could be operated in browser/server mode, which gives the possibility to use it anywhere the internet is accessible. By switchingmore » the nuclide library and the related formula behind, the new software can be easily expanded to neutron activation analysis (NAA), charged particle activation analysis (CPAA) or proton-induced X-ray emission (PIXE). Implementation of this would standardize the analysis of nuclear activation data. Results from this software were compared to standard PAA analysis with excellent agreement. With minimum input from the user, the software has proven to be fast, user-friendly and reliable.« less

Cadmium concentrations in the brains of Alzheimer cases

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

Spyrou, N.M.; Stedman, J.D.

1996-12-31

There is ongoing research in relating the concentration of elements in the brain with Alzheimer`s disease. The presence of particular elements, such as aluminum and vanadium, has been considered as a possible environmental factor, creating significant interest and controversy in the field. We have been analyzing brain tissue from the MRC Alzheimer`s Disease Brain Bank, Institute of Psychiatry, from a number of cortical regions of the brain, namely, the frontal, occipital, parietal, and temporal lobes, as well as from the left and right hemispheres of the same brain whenever possible. The techniques employed have been proton-induced X-ray emission (PIXE) analysis,more » proton-induced gamma-ray emission (PIGE) analysis, Rutherford backscattering (RBS), and instrumental neutron activation analysis. Neutron irradiations were carried out at the Imperial College Consort II reactor, whereas for PIXE, PIGE, and RBS, the University of Surrey Accelerator Laboratories were used employing a Van de Graaff accelerator. In this paper, we present the cadmium results from the frontal lobe of Alzheimer cases and controls determined by PIXE analysis.« less

Improving the modelling of irradiation-induced brain activation for in vivo PET verification of proton therapy.

PubMed

Bauer, Julia; Chen, Wenjing; Nischwitz, Sebastian; Liebl, Jakob; Rieken, Stefan; Welzel, Thomas; Debus, Juergen; Parodi, Katia

2018-04-24

A reliable Monte Carlo prediction of proton-induced brain tissue activation used for comparison to particle therapy positron-emission-tomography (PT-PET) measurements is crucial for in vivo treatment verification. Major limitations of current approaches to overcome include the CT-based patient model and the description of activity washout due to tissue perfusion. Two approaches were studied to improve the activity prediction for brain irradiation: (i) a refined patient model using tissue classification based on MR information and (ii) a PT-PET data-driven refinement of washout model parameters. Improvements of the activity predictions compared to post-treatment PT-PET measurements were assessed in terms of activity profile similarity for six patients treated with a single or two almost parallel fields delivered by active proton beam scanning. The refined patient model yields a generally higher similarity for most of the patients, except in highly pathological areas leading to tissue misclassification. Using washout model parameters deduced from clinical patient data could considerably improve the activity profile similarity for all patients. Current methods used to predict proton-induced brain tissue activation can be improved with MR-based tissue classification and data-driven washout parameters, thus providing a more reliable basis for PT-PET verification. Copyright © 2018 Elsevier B.V. All rights reserved.

To flow or not to flow : a study of elliptic flow and nonflow in proton-proton collisions in ALICE

NASA Astrophysics Data System (ADS)

van der Kolk, N.

2012-01-01

The standard model of particle physics describes all known elementary particles and the forces between them. The strong force, which binds quarks inside hadrons and nucleons inside nuclei, is described by the theory of Quantum Chromodynamics. This theory predicts a new state of matter at extreme temperatures and densities: the Quark Gluon plasma. The ALICE experiment at the Large Hadron Collider near Geneva was build to study this QGP by looking at collisions of the most heavy stable ions: lead (Pb) ions. In such collisions one hopes to achieve sufficient energy density for the creation of a QGP. One of the signatures of QGP formation in high energy heavy ion collisions is the presence of collective behaviour in the system formed during the collision. This collectivity manifests itself in a common velocity in all produced particles: a collective flow. The most dominant contribution to collective flow is elliptic flow, which originates from the anisotropic overlap region of the two nuclei in non-central collisions and is visible in the azimuthal distribution of the produced particles. Elliptic flow is related to the equation of state of the system and its degree of thermalisation. The analysis of elliptic flow is complicated by the presence of correlations between particles from other sources, summarised in the term nonflow. Several analysis methods have become available over the years and have been implemented for elliptic flow analysis within the ALICE computing framework. These methods have different sensitivities to these nonflow correlations. Because the centre of mass energy at the LHC is so high, predictions have been made of collective behaviour even in proton-proton collisions. These predictions are very divers and give values between 0 and 0.2 for elliptic flow using different models. To constrain these predictions proton-proton data, recorded with the ALICE experiment at the LHC in the 2010 7 TeV proton-proton run, was studied. In proton-proton collisions large nonflow correlations are certainly present and might mask the elliptic flow correlation. The nonflow correlations have to be suppressed sufficiently such that the elliptic flow signal becomes detectable. Therefor an analysis method was choosen that can suppress nonflow correlations by increasing the separation in pseudorapidity of two subevents. This method is called the scalar product method. How much nonflow is suppressed is shown to depend on the pseudorapidity range of the nonflow. The dependence on the pseudorapidity gap size between the subevents, in 7 TeV proton-proton collisions, points to a strong nonflow component, because the signal decreases with increasing gap size. The corresponding Monte Carlo data set shows the same dependence, while it only includes nonflow correlations. This enforces the conclusion that nonflow is the dominant or the only correlation in 7 TeV proton-proton data at the LHC. The conclusion from this analysis is that elliptic flow in 7 TeV proton-proton collisions with at least 10 particles is less than 0.05. Predictions of a higher elliptic flow for these events can be excluded. To exclude or confirm lower predicted values the nonflow contribution has to be further reduced.

Effects of protonation state of Asp181 and position of active site water molecules on the conformation of PTP1B.

PubMed

Ozcan, Ahmet; Olmez, Elif Ozkirimli; Alakent, Burak

2013-05-01

In protein tyrosine phosphatase 1B (PTP1B), the flexible WPD loop adopts a closed conformation (WPDclosed ) in the active state of PTP1B, bringing the catalytic Asp181 close to the active site pocket, while WPD loop is in an open conformation (WPDopen ) in the inactive state. Previous studies showed that Asp181 may be protonated at physiological pH, and ordered water molecules exist in the active site. In the current study, molecular dynamics simulations are employed at different Asp181 protonation states and initial positions of active site water molecules, and compared with the existing crystallographic data of PTP1B. In WPDclosed conformation, the active site is found to maintain its conformation only in the protonated state of Asp181 in both free and liganded states, while Asp181 is likely to be deprotonated in WPDopen conformation. When the active site water molecule network that is a part of the free WPDclosed crystal structure is disrupted, intermediate WPD loop conformations, similar to that in the PTPRR crystal structure, are sampled in the MD simulations. In liganded PTP1B, one active site water molecule is found to be important for facilitating the orientation of Cys215 and the phosphate ion, thus may play a role in the reaction. In conclusion, conformational stability of WPD loop, and possibly catalytic activity of PTP1B, is significantly affected by the protonation state of Asp181 and position of active site water molecules, showing that these aspects should be taken into consideration both in MD simulations and inhibitor design. Copyright © 2013 Wiley Periodicals, Inc.

Recent Advances in Understanding Radiation Belt Dynamics in the Earth's Inner Zone and Slot Region

NASA Astrophysics Data System (ADS)

Li, X.

2015-12-01

Comprehensive measurements of the inner belt protons from the Relativistic Electron and Proton Telescope (REPT) onboard Van Allen Probes, in a geo-transfer-like orbit, revealed new features of inner belt protons in terms of their spectrum distribution, spatial distribution, pitch angle distribution, and their different source populations. Concurrent measurements from the Relativistic Electron and Proton Telescope integrated little experiment (REPTile) on board Colorado Student Space Weather Experiment (CSSWE) CubeSat, in a highly inclined low Earth orbit, and REPT demonstrated that there exist sub-MeV electrons in the inner belt and their flux level is orders of magnitude higher than the background associated with the inner belt protons, while higher energy electron (>1.6 MeV) measurements cannot be distinguished from the background. Analysis on sub-MeV electrons data in the inner belt and slot region from the Magnetic Electron Ion Spectrometer (MagEIS) on board Van Allen Probes revealed rather complicated pitch angle distribution of these energetic electrons, with the 90 deg-minimum (butterfly) pitch angle distribution dominating near the magnetic equator. Furthermore, it is clearly shown from MagEIS measurements that 10s - 100s keV electrons are commonly seen penetrating into the inner belt region during geomagnetic active times while protons of similar energies are hardly seen there. These are part of a summary of the most recent measurements and understanding of the dynamics of energetic particles in the inner zone and slot region to be exhibited and discussed in this presentation.

1000-fold enhancement in proton conductivity of a MOF using post-synthetically anchored proton transporters

PubMed Central

Shalini, Sorout; Dhavale, Vishal M.; Eldho, Kavalakal M.; Kurungot, Sreekumar; Ajithkumar, Thallaseril G.; Vaidhyanathan, Ramanathan

2016-01-01

Pyridinol, a coordinating zwitter-ionic species serves as stoichiometrically loadable and non-leachable proton carrier. The partial replacement of the pyridinol by stronger hydrogen bonding, coordinating guest, ethylene glycol (EG), offers 1000-fold enhancement in conductivity (10−6 to 10−3 Scm−1) with record low activation energy (0.11 eV). Atomic modeling coupled with 13C-SSNMR provides insights into the potential proton conduction pathway functionalized with post-synthetically anchored dynamic proton transporting EG moieties. PMID:27577681

Proton radiography and tomography with application to proton therapy

PubMed Central

Allinson, N M; Evans, P M

2015-01-01

Proton radiography and tomography have long promised benefit for proton therapy. Their first suggestion was in the early 1960s and the first published proton radiographs and CT images appeared in the late 1960s and 1970s, respectively. More than just providing anatomical images, proton transmission imaging provides the potential for the more accurate estimation of stopping-power ratio inside a patient and hence improved treatment planning and verification. With the recent explosion in growth of clinical proton therapy facilities, the time is perhaps ripe for the imaging modality to come to the fore. Yet many technical challenges remain to be solved before proton CT scanners become commonplace in the clinic. Research and development in this field is currently more active than at any time with several prototype designs emerging. This review introduces the principles of proton radiography and tomography, their historical developments, the raft of modern prototype systems and the primary design issues. PMID:26043157

Purification and Functional Reconstitution of a Seven-Subunit Mrp-Type Na+/H+ Antiporter

PubMed Central

Morino, Masato; Suzuki, Toshiharu; Ito, Masahiro

2014-01-01

Mrp antiporters and their homologues in the cation/proton antiporter 3 family of the Membrane Transporter Database are widely distributed in bacteria. They have major roles in supporting cation and cytoplasmic pH homeostasis in many environmental, extremophilic, and pathogenic bacteria. These antiporters require six or seven hydrophobic proteins that form hetero-oligomeric complexes, while most other cation/proton antiporters require only one membrane protein for their activity. The resemblance of three Mrp subunits to membrane-embedded subunits of the NADH:quinone oxidoreductase of respiratory chains and to subunits of several hydrogenases has raised interest in the evolutionary path and commonalities of their proton-translocating domains. In order to move toward a greater mechanistic understanding of these unusual antiporters and to rigorously demonstrate that they function as secondary antiporters, powered by an imposed proton motive force, we established a method for purification and functional reconstitution of the seven-subunit Mrp antiporter from alkaliphilic Bacillus pseudofirmus OF4. Na+/H+ antiporter activity was demonstrated by a fluorescence-based assay with proteoliposomes in which the Mrp complex was coreconstituted with a bacterial FoF1-ATPase. Proton pumping by the ATPase upon addition of ATP generated a proton motive force across the membranes that powered antiporter activity upon subsequent addition of Na+. PMID:24142251

Purification and functional reconstitution of a seven-subunit mrp-type na+/h+ antiporter.

PubMed

Morino, Masato; Suzuki, Toshiharu; Ito, Masahiro; Krulwich, Terry Ann

2014-01-01

Mrp antiporters and their homologues in the cation/proton antiporter 3 family of the Membrane Transporter Database are widely distributed in bacteria. They have major roles in supporting cation and cytoplasmic pH homeostasis in many environmental, extremophilic, and pathogenic bacteria. These antiporters require six or seven hydrophobic proteins that form hetero-oligomeric complexes, while most other cation/proton antiporters require only one membrane protein for their activity. The resemblance of three Mrp subunits to membrane-embedded subunits of the NADH:quinone oxidoreductase of respiratory chains and to subunits of several hydrogenases has raised interest in the evolutionary path and commonalities of their proton-translocating domains. In order to move toward a greater mechanistic understanding of these unusual antiporters and to rigorously demonstrate that they function as secondary antiporters, powered by an imposed proton motive force, we established a method for purification and functional reconstitution of the seven-subunit Mrp antiporter from alkaliphilic Bacillus pseudofirmus OF4. Na(+)/H(+) antiporter activity was demonstrated by a fluorescence-based assay with proteoliposomes in which the Mrp complex was coreconstituted with a bacterial FoF1-ATPase. Proton pumping by the ATPase upon addition of ATP generated a proton motive force across the membranes that powered antiporter activity upon subsequent addition of Na(+).

Development of Technology for Image-Guided Proton Therapy

DTIC Science & Technology

2011-10-01

testing proton RBE in the Penn proton beam facility  Assemble equipment and develop data analysis software  Install and test tablet PCs...production  Use dual-energy CT and MRI to determine the composition of materials Year 4 ending 9/30/2011  Measurement of RBE for protons using the...Penn proton beam facility  Measure LET for scattered and scanned beams  Enter forms on tablet PCs Phase 5 Scope of Work Year 1 ending 9

An analysis of beam parameters on proton-acoustic waves through an analytic approach.

PubMed

Kipergil, Esra Aytac; Erkol, Hakan; Kaya, Serhat; Gulsen, Gultekin; Unlu, Mehmet Burcin

2017-06-21

It has been reported that acoustic waves are generated when a high-energy pulsed proton beam is deposited in a small volume within tissue. One possible application of proton-induced acoustics is to get real-time feedback for intra-treatment adjustments by monitoring such acoustic waves. A high spatial resolution in ultrasound imaging may reduce proton range uncertainty. Thus, it is crucial to understand the dependence of the acoustic waves on the proton beam characteristics. In this manuscript, firstly, an analytic solution for the proton-induced acoustic wave is presented to reveal the dependence of the signal on the beam parameters; then it is combined with an analytic approximation of the Bragg curve. The influence of the beam energy, pulse duration and beam diameter variation on the acoustic waveform are investigated. Further analysis is performed regarding the Fourier decomposition of the proton-acoustic signals. Our results show that the smaller spill time of the proton beam upsurges the amplitude of the acoustic wave for a constant number of protons, which is hence beneficial for dose monitoring. The increase in the energy of each individual proton in the beam leads to the spatial broadening of the Bragg curve, which also yields acoustic waves of greater amplitude. The pulse duration and the beam width of the proton beam do not affect the central frequency of the acoustic wave, but they change the amplitude of the spectral components.

Preliminary results of an in-beam PET prototype for proton therapy

NASA Astrophysics Data System (ADS)

Attanasi, F.; Belcari, N.; Camarda, M.; Cirrone, G. A. P.; Cuttone, G.; Del Guerra, A.; Di Rosa, F.; Lanconelli, N.; Rosso, V.; Russo, G.; Vecchio, S.

2008-06-01

Proton therapy can overcome the limitations of conventional radiotherapy due to the more selective energy deposition in depth and to the increased biological effectiveness. Verification of the delivered dose is desirable, but the complete stopping of the protons in patient prevents the application of electronic portal imaging methods that are used in conventional radiotherapy During proton therapy β + emitters like 11C, 15O, 10C are generated in irradiated tissues by nuclear reactions. The measurement of the spatial distribution of this activity, immediately after patient irradiation, can lead to information on the effective delivered dose. First, results of a feasibility study of an in-beam PET for proton therapy are reported. The prototype is based on two planar heads with an active area of about 5×5 cm 2. Each head is made up of a position sensitive photomultiplier coupled to a square matrix of same size of LYSO scintillating crystals (2×2×18 mm 3 pixel dimensions). Four signals from each head are acquired through a dedicated electronic board that performs signal amplification and digitization. A 3D reconstruction of the activity distribution is calculated using an expectation maximization algorithm. To characterize the PET prototype, the detection efficiency and the spatial resolution were measured using a point-like radioactive source. The validation of the prototype was performed using 62 MeV protons at the CATANA beam line of INFN LNS and PMMA phantoms. Using the full energy proton beam and various range shifters, a good correlation between the position of the activity distal edge and the thickness of the beam range shifter was found along the axial direction.

Synthesis, crystal structure and antitumor activities of water soluble protonated salt of 20(S)-camptothecin

NASA Astrophysics Data System (ADS)

Lu, Wen; Wang, Yong; Wang, Luna; Zhao, Fengyi; Yang, Shilong; Xi, Chengjie; Yang, Yu; Xu, Li; Chi, Xingwei

2018-03-01

A water soluble camptothecin protonated salt has been synthesized; single crystals were grown by slow evaporation solution growth technique at room temperature and characterized by single crystal X-ray diffraction, FT-IR and 1H NMR. The CPT was protonated as (CPT+H+) cations, the cationic protonation occurred on the N position at pyridine group, which fromed a cation-anion compound with perchlorate ion that determined by X-Ray diffraction. Its activities against Hela (cervix), MCF-7 (breast), A549 (lung), HepG2 (liver) and HUVEC (umbilical vein, normal cell) were investigated. The toxicity of the protonated salt was slightly lower than camptothecin. IC50 values of 7.01 μM against HepG-2 cell, 8.61 μM against A549 cell, 17.82 μM against McF-7 cell, all of them are lower than the IC50 values of CPT against these cells except Hela cell.

Protons Regulate Vesicular Glutamate Transporters through an Allosteric Mechanism.

PubMed

Eriksen, Jacob; Chang, Roger; McGregor, Matt; Silm, Katlin; Suzuki, Toshiharu; Edwards, Robert H

2016-05-18

The quantal nature of synaptic transmission requires a mechanism to transport neurotransmitter into synaptic vesicles without promoting non-vesicular efflux across the plasma membrane. Indeed, the vesicular transport of most classical transmitters involves a mechanism of H(+) exchange, which restricts flux to acidic membranes such as synaptic vesicles. However, vesicular transport of the principal excitatory transmitter glutamate depends primarily on membrane potential, which would drive non-vesicular efflux, and the role of protons is unclear. Adapting electrophysiology to record currents associated with the vesicular glutamate transporters (VGLUTs), we characterize a chloride conductance that is gated by lumenal protons and chloride and supports glutamate uptake. Rather than coupling stoichiometrically to glutamate flux, lumenal protons and chloride allosterically activate vesicular glutamate transport. Gating by protons serves to inhibit what would otherwise be substantial non-vesicular glutamate efflux at the plasma membrane, thereby restricting VGLUT activity to synaptic vesicles. Copyright © 2016 Elsevier Inc. All rights reserved.

[Interaction of surface-active base with fraction of membrane-bound Williams's protons].

PubMed

Iaguzhinskiĭ, L S; Motovilov, K A; Volkov, E M; Eremeev, S A

2013-01-01

In the process of mitochondrial respiratory H(+)-pumps functioning, the fraction membrane-bound protons (R-protons), which have an excess of free energy is formed. According to R.J. Williams this fraction is included as energy source in the reaction of ATP synthesis. Previously, in our laboratory was found the formation of this fraction was found in the mitochondria and on the outer surface of mitoplast. On the mitoslast model we strictly shown that non-equilibrium R-proton fraction is localized on the surface of the inner mitochondrial membrane. In this paper a surface-active compound--anion of 2,4,6-trichloro-3-pentadecylphenol (TCP-C15) is described, which selectively interacts with the R-protons fraction in mitochondria. A detailed description of the specific interaction of the TCP-C15 with R-protons fraction in mitochondria is presented. Moreover, in this work it was found that phosphate transport system reacts with the R-protons fraction in mitochondria and plays the role of the endogenous volume regulation system of this fraction. The results of experiments are discussed in the terms of a local coupling model of the phosphorylation mechanism.

Tuning of Nafion® by HKUST-1 as coordination network to enhance proton conductivity for fuel cell applications

NASA Astrophysics Data System (ADS)

Kim, Hee Jin; Talukdar, Krishan; Choi, Sang-June

2016-02-01

Metal-organic frameworks can be intentionally coordinated to achieve improved proton conductivity because they have highly ordered structures and modular nature that serve as a scaffold to anchor acidic groups and develop efficient proton transfer pathways for fuel cell application. Using the concept of a coordination network, the conductivity of Nafion® was tuned by the incorporation of HKUST-1. It has CuII-paddle wheel type nodes and 1,3,5-benzenetricarboxylate struts, feature accessible sites that provides an improved protonic channel depending on the water content. In spite of the fact that HKUST-1 is neutral, coordinated water molecules are contributed adequately acidic by CuII to supply protons to enhance proton conductivity. Water molecules play a vital part in transfer of proton as conducting media and serve as triggers to change proton conductivity through reforming hydrogen bonding networks by water adsorption/desorption process. Increased ion exchange capacity and proton conductivity with lower water uptake of the H3PO4-doped material, and improved thermal stability (as confirmed by thermogravimetric analysis) were achieved. The structure of HKUST-1 was confirmed via field emission scanning electron microscopy and X-ray diffraction, while the porosity and adsorption desorption capacity were characterized by porosity analysis.

Two zebrafish G2A homologs activate multiple intracellular signaling pathways in acidic environment.

PubMed

Ichijo, Yuta; Mochimaru, Yuta; Azuma, Morio; Satou, Kazuhiro; Negishi, Jun; Nakakura, Takashi; Oshima, Natsuki; Mogi, Chihiro; Sato, Koichi; Matsuda, Kouhei; Okajima, Fumikazu; Tomura, Hideaki

2016-01-01

Human G2A is activated by various stimuli such as lysophosphatidylcholine (LPC), 9-hydroxyoctadecadienoic acid (9-HODE), and protons. The receptor is coupled to multiple intracellular signaling pathways, including the Gs-protein/cAMP/CRE, G12/13-protein/Rho/SRE, and Gq-protein/phospholipase C/NFAT pathways. In the present study, we examined whether zebrafish G2A homologs (zG2A-a and zG2A-b) could respond to these stimuli and activate multiple intracellular signaling pathways. We also examined whether histidine residue and basic amino acid residue in the N-terminus of the homologs also play roles similar to those played by human G2A residues if the homologs sense protons. We found that the zG2A-a showed the high CRE, SRE, and NFAT activities, however, zG2A-b showed only the high SRE activity under a pH of 8.0. Extracellular acidification from pH 7.4 to 6.3 ameliorated these activities in zG2A-a-expressing cells. On the other hand, acidification ameliorated the SRE activity but not the CRE and NFAT activities in zG2A-b-expressing cells. LPC or 9-HODE did not modify any activity of either homolog. The substitution of histidine residue at the 174(th) position from the N-terminus of zG2A-a to asparagine residue attenuated proton-induced CRE and NFAT activities but not SRE activity. The substitution of arginine residue at the 32nd position from the N-terminus of zG2A-a to the alanine residue also attenuated its high and the proton-induced CRE and NFAT activities. On the contrary, the substitution did not attenuate SRE activity. The substitution of the arginine residue at the 10th position from the N-terminus of zG2A-b to the alanine residue also did not attenuate its high or the proton-induced SRE activity. These results indicate that zebrafish G2A homologs were activated by protons but not by LPC and 9-HODE, and the activation mechanisms of the homologs were similar to those of human G2A. Copyright © 2015 Elsevier Inc. All rights reserved.

The Catalase Activity of Catalase-Peroxidases Is Modulated by Changes in the pKa of the Distal Histidine.

PubMed

Machuqueiro, Miguel; Victor, Bruno; Switala, Jacek; Villanueva, Jacylyn; Rovira, Carme; Fita, Ignacio; Loewen, Peter C

2017-05-02

The unusual Met-Tyr-Trp adduct composed of cross-linked side chains along with an associated mobile Arg is essential for catalase activity in catalase-peroxidases. In addition, acidic residues in the entrance channel, in particular an Asp and a Glu ∼7 and ∼15 Å, respectively, from the heme, significantly enhance catalase activity. The mechanism by which these channel carboxylates influence catalase activity is the focus of this work. Seventeen new variants with fewer and additional acidic residues have been constructed and characterized structurally and for enzymatic activity, revealing that their effect on activity is roughly inversely proportional to their distance from the heme and adduct, suggesting that the electrostatic potential of the heme cavity may be affected. A discrete group of protonable residues are contained within a 15 Å sphere surrounding the heme iron, and a computational analysis reveals that the pK a of the distal His 112 , alone, is modulated within the pH range of catalase activity by the remote acidic residues in a pattern consistent with its protonated form having a key role in the catalase reaction cycle. The electrostatic potential also impacts the catalatic reaction through its influence on the charged status of the Met-Tyr-Trp adduct.

Proton and deuteron activation measurements at the NPI and future plans in SPIRAL2/NFS

NASA Astrophysics Data System (ADS)

Šimečková, Eva; Bém, Pavel; Mrázek, Jaromír; Štefánik, Milan; Běhal, Radomír; Gladolev, Vadim

2017-09-01

The proton- and deuteron-induced reactions are of a great interest for the assessment of induced radioactivity of accelerator components, target and beam stoppers as well as isotope production for medicine. In the present work, the deuteron-induced reaction cross sections on zinc were investigated by stacked-foil activation technique with deuteron beam of 20 MeV energy from the cyclotron U-120M of NPI CAS Řež. Also the proton activation cross section measurement of iron is presented. The comparison of present results to data of other authors and to predictions of evaluated data libraries is discussed. The investigation shall continue for higher proton and deuteron energy interval 20-35 MeV at SPIRAL2/NFS facility using a charged particle irradiation chamber with pneumatic transport system to measure isotopes and isomers with half-lives in minutes-regions.

Measurement of the underlying event activity in inclusive Z boson production in proton-proton collisions at $$\\sqrt{s} = $$ 13 TeV

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

Sirunyan, Albert M; et al.

This paper presents a measurement of the underlying event activity in proton-proton collisions at a center-of-mass energy of 13 TeV, performed using inclusive Z boson production events collected with the CMS experiment at the LHC. The analyzed data correspond to an integrated luminosity of 2.1 fbmore » $$^{-1}$$. The underlying event activity is quantified in terms of the charged particle multiplicity, as well as of the scalar sum of the charged particles' transverse momenta in different topological regions defined with respect to the Z boson direction. The distributions are unfolded to the stable particle level and compared with predictions from various Monte Carlo event generators, as well as with similar CDF and CMS measurements at center-of-mass energies of 1.96 and 7 TeV respectively.« less

Proton-coupled electron transfer in the catalytic cycle of Alcaligenes xylosoxidans copper-dependent nitrite reductase.

PubMed

Leferink, Nicole G H; Han, Cong; Antonyuk, Svetlana V; Heyes, Derren J; Rigby, Stephen E J; Hough, Michael A; Eady, Robert R; Scrutton, Nigel S; Hasnain, S Samar

2011-05-17

We demonstrated recently that two protons are involved in reduction of nitrite to nitric oxide through a proton-coupled electron transfer (ET) reaction catalyzed by the blue Cu-dependent nitrite reductase (Cu NiR) of Alcaligenes xylosoxidans (AxNiR). Here, the functionality of two putative proton channels, one involving Asn90 and the other His254, is studied using single (N90S, H254F) and double (N90S--H254F) mutants. All mutants studied are active, indicating that protons are still able to reach the active site. The H254F mutation has no effect on the catalytic activity, while the N90S mutation results in ~70% decrease in activity. Laser flash-photolysis experiments show that in H254F and wild-type enzyme electrons enter at the level of the T1Cu and then redistribute between the two Cu sites. Complete ET from T1Cu to T2Cu occurs only when nitrite binds at the T2Cu site. This indicates that substrate binding to T2Cu promotes ET from T1Cu, suggesting that the enzyme operates an ordered mechanism. In fact, in the N90S and N90S--H254F variants, where the T1Cu site redox potential is elevated by ∼60 mV, inter-Cu ET is only observed in the presence of nitrite. From these results it is evident that the Asn90 channel is the main proton channel in AxNiR, though protons can still reach the active site if this channel is disrupted. Crystallographic structures provide a clear structural rationale for these observations, including restoration of the proton delivery via a significant movement of the loop connecting the T1Cu ligands Cys130 and His139 that occurs on binding of nitrite. Notably, a role for this loop in facilitating interaction of cytochrome c(551) with Cu NiR has been suggested previously based on a crystal structure of the binary complex.

Role of Water in Proton-Hydroxide Conductance Across Model and Biological Membranes

DTIC Science & Technology

1990-09-01

esearch - CONTRACT TITLE: Role of water in proton-hydroxide conductan, e across model Maim and biological membranes. RESEARCH OBJECTIVES: Our goals over...establish a model system for measuring proton flux along hydrogen bonded chains of water in hydrophobic phases. TRAINING ACTIVITIES: Three doctoral and two...to general anesthetics. Biochim. Biophys. Acta 944:40- 48. 6. Deamer, D.W. and Nichols, J.W. (1989) Proton flux in model and biological membranes. J

Beyond Gaussians: a study of single spot modeling for scanning proton dose calculation

PubMed Central

Li, Yupeng; Zhu, Ronald X.; Sahoo, Narayan; Anand, Aman; Zhang, Xiaodong

2013-01-01

Active spot scanning proton therapy is becoming increasingly adopted by proton therapy centers worldwide. Unlike passive-scattering proton therapy, active spot scanning proton therapy, especially intensity-modulated proton therapy, requires proper modeling of each scanning spot to ensure accurate computation of the total dose distribution contributed from a large number of spots. During commissioning of the spot scanning gantry at the Proton Therapy Center in Houston, it was observed that the long-range scattering protons in a medium may have been inadequately modeled for high-energy beams by a commercial treatment planning system, which could lead to incorrect prediction of field-size effects on dose output. In the present study, we developed a pencil-beam algorithm for scanning-proton dose calculation by focusing on properly modeling individual scanning spots. All modeling parameters required by the pencil-beam algorithm can be generated based solely on a few sets of measured data. We demonstrated that low-dose halos in single-spot profiles in the medium could be adequately modeled with the addition of a modified Cauchy-Lorentz distribution function to a double-Gaussian function. The field-size effects were accurately computed at all depths and field sizes for all energies, and good dose accuracy was also achieved for patient dose verification. The implementation of the proposed pencil beam algorithm also enabled us to study the importance of different modeling components and parameters at various beam energies. The results of this study may be helpful in improving dose calculation accuracy and simplifying beam commissioning and treatment planning processes for spot scanning proton therapy. PMID:22297324

Proton Irradiation-Induced Metal Voids in Gallium Nitride High Electron Mobility Transistors

DTIC Science & Technology

2015-09-01

13. ABSTRACT (maximum 200 words) Gallium nitride/aluminum gallium nitride high electron mobility transistors with nickel/ gold (Ni/Au) and...platinum/ gold (Pt/Au) gating are irradiated with 2 MeV protons. Destructive physical analysis revealed material voids underneath the gate finger of the...nickel/ gold (Ni/Au) and platinum/ gold (Pt/Au) gating are irradiated with 2 MeV protons. Destructive physical analysis revealed material voids underneath

Periods of High Intensity Solar Proton Flux

NASA Technical Reports Server (NTRS)

Xapsos, Michael A.; Stauffer, Craig A.; Jordan, Thomas M.; Adams, James H.; Dietrich, William F.

2012-01-01

Analysis is presented for times during a space mission that specified solar proton flux levels are exceeded. This includes both total time and continuous time periods during missions. Results for the solar maximum and solar minimum phases of the solar cycle are presented and compared for a broad range of proton energies and shielding levels. This type of approach is more amenable to reliability analysis for spacecraft systems and instrumentation than standard statistical models.

ß-delayed γ-proton decay in ⁵⁶Zn: Analysis of the charged-particle spectrum

DOE PAGES

Orrigo, S. E.A.; Rubio, B.; Fujita, Y.; ...

2015-01-01

A study of the β decay of the proton-rich T z = –2 nucleus ⁵⁶Zn has been reported in a recent publication. A rare and exotic decay mode, β-de-layed γ-proton decay, has been observed there for the first time in the fp shell. Here, we expand on some of the details of the data analysis, focusing on the charged particle spectrum.

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.

Pt nanoparticle-reduced graphene oxide nanohybrid for proton exchange membrane fuel cells.

PubMed

Park, Dae-Hwan; Jeon, Yukwon; Ok, Jinhee; Park, Jooil; Yoon, Seong-Ho; Choy, Jin-Ho; Shul, Yong-Gun

2012-07-01

A platinum nanoparticle-reduced graphene oxide (Pt-RGO) nanohybrid for proton exchange membrane fuel cell (PEMFC) application was successfully prepared. The Pt nanoparticles (Pt NPs) were deposited onto chemically converted graphene nanosheets via ethylene glycol (EG) reduction. According to the powder X-ray diffraction (XRD) pattern and transmission electron microscopy (TEM) analysis, the face-centered cubic Pt NPs (3-5 nm in diameter) were homogeneously dispersed on the RGO nanosheets. The electrochemically active surface area and PEMFC power density of the Pt-RGO nanohybrid were determined to be 33.26 m2/g and 480 mW/cm2 (maximum values), respectively, at 75 degrees C and at a relative humidity (RH) of 100% in a single-cell test experiment.

Superasymmetric fission of heavy nuclei induced by intermediate-energy protons

NASA Astrophysics Data System (ADS)

Deppman, A.; Andrade-II, E.; Guimarães, V.; Karapetyan, G. S.; Tavares, O. A. P.; Balabekyan, A. R.; Demekhina, N. A.; Adam, J.; Garcia, F.; Katovsky, K.

2013-12-01

In this work we present the results for the investigation of intermediate-mass fragment (IMF) production with the proton-induced reaction at 660 MeV on 238U and 237Np target. The data were obtained with the LNR Phasotron U-400M Cyclotron at Joint Institute for Nuclear Research (JINR), Dubna, Russia. A total of 93 isotopes, in the mass range of 30

Establishing Cost-Effective Allocation of Proton Therapy for Breast Irradiation

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

Mailhot Vega, Raymond B.; Ishaq, Omar; Raldow, Ann

Purpose: Cardiac toxicity due to conventional breast radiation therapy (RT) has been extensively reported, and it affects both the life expectancy and quality of life of affected women. Given the favorable oncologic outcomes in most women irradiated for breast cancer, it is increasingly paramount to minimize treatment side effects and improve survivorship for these patients. Proton RT offers promise in limiting heart dose, but the modality is costly and access is limited. Using cost-effectiveness analysis, we provide a decision-making tool to help determine which breast cancer patients may benefit from proton RT referral. Methods and Materials: A Markov cohort model wasmore » constructed to compare the cost-effectiveness of proton versus photon RT for breast cancer management. The model was analyzed for different strata of women based on age (40 years, 50 years, and 60 years) and the presence or lack of cardiac risk factors (CRFs). Model entrants could have 1 of 3 health states: healthy, alive with coronary heart disease (CHD), or dead. Base-case analysis assumed CHD was managed medically. No difference in tumor control was assumed between arms. Probabilistic sensitivity analysis was performed to test model robustness and the influence of including catheterization as a downstream possibility within the health state of CHD. Results: Proton RT was not cost-effective in women without CRFs or a mean heart dose (MHD) <5 Gy. Base-case analysis noted cost-effectiveness for proton RT in women with ≥1 CRF at an approximate minimum MHD of 6 Gy with a willingness-to-pay threshold of $100,000/quality-adjusted life-year. For women with ≥1 CRF, probabilistic sensitivity analysis noted the preference of proton RT for an MHD ≥5 Gy with a similar willingness-to-pay threshold. Conclusions: Despite the cost of treatment, scenarios do exist whereby proton therapy is cost-effective. Referral for proton therapy may be cost-effective for patients with ≥1 CRF in cases for which photon plans are unable to achieve an MHD <5 Gy.« less

Measurements of the u valence quark distribution function in the proton and u quark fragmentation functions

NASA Astrophysics Data System (ADS)

Arneodo, M.; Arvidson, A.; Aubert, J. J.; Badelek, B.; Beaufays, J.; Bee, C. P.; Benchouk, C.; Berghoff, G.; Bird, I. G.; Blum, D.; Böhm, E.; De Bouard, X.; Brasse, F. W.; Braun, H.; Broll, C.; Brown, S. C.; Brück, H.; Calen, H.; Chima, J. S.; Ciborowski, J.; Clifft, R.; Coignet, G.; Combley, F.; Coughlan, J.; D'Agostini, G.; Dahlgren, S.; Dengler, F.; Derado, I.; Dreyer, T.; Drees, J.; Düren, M.; Eckardt, V.; Edwards, A.; Edwards, M.; Ernst, T.; Eszes, G.; Favier, J.; Ferrero, M. I.; Figiel, J.; Flauger, W.; Foster, J.; Gabathuler, E.; Gajewski, J.; Gamet, R.; Gayler, J.; Geddes, N.; Grafström, P.; Grard, F.; Haas, J.; Hagberg, E.; Hasert, F. J.; Hayman, P.; Heusse, P.; Jaffre, M.; Jacholkowska, A.; Janata, F.; Jancso, G.; Johnson, A. S.; Kabuss, E. M.; Kellner, G.; Korbel, V.; Krüger, A.; Krüger, J.; Kullander, S.; Landgraf, U.; Lanske, D.; Loken, J.; Long, K.; Maire, M.; Malecki, P.; Manz, A.; Maselli, S.; Mohr, W.; Montanet, F.; Montgomery, H. E.; Nagy, E.; Nassalski, J.; Norton, P. R.; Oakham, F. G.; Osborne, A. M.; Pascaud, C.; Pawlik, B.; Payre, P.; Peroni, C.; Peschel, H.; Pessard, H.; Pettingale, J.; Pietrzyk, B.; Poensgen, B.; Pötsch, M.; Renton, P.; Ribarics, P.; Rith, K.; Rondio, E.; Sandacz, A.; Scheer, M.; Schlagböhmer, A.; Schiemann, H.; Schmitz, N.; Schneegans, M.; Scholz, M.; Schouten, M.; Schröder, T.; Schultze, K.; Sloan, T.; Stier, H. E.; Studt, M.; Taylor, G. N.; Thenard, J. M.; Thompson, J. C.; De la Torre, A.; Toth, J.; Urban, L.; Urban, L.; Wallucks, W.; Whalley, M.; Wheeler, S.; Williams, W. S. C.; Wimpenny, S. J.; Windmolders, R.; Wolf, G.; European Muon Collaboration

1989-07-01

A new determination of the u valence quark distribution function in the proton is obtained from the analysis of identified charged pions, kaons, protons and antiprotons produced in muon-proton and muon-deuteron scattering. The comparison with results obtained in inclusive deep inelastic lepton-nucleon scattering provides a further test of the quark-parton model. The u quark fragmentation functions into positive and negative pions, kaons, protons and antiprotons are also measured.

Analysis of Proton Radiation Effects on Gallium Nitride High Electron Mobility Transistors

DTIC Science & Technology

2017-03-01

energy levels on a GaN-on-silicon high electron mobility transistor was created. Based on physical results of 2.0-MeV protons irradiation to fluence...and the physical device at 2.0-MeV proton irradiation , predictions were made for 5.0, 10.0, 20.0 and 40.0-MeV proton irradiation . The model generally...nitride, high electron mobility transistor, electronics, 2 MeV proton irradiation , radiation effects 15. NUMBER OF PAGES 87 16. PRICE CODE 17. SECURITY

Protonation enthalpies of metal oxides from high temperature electrophoresis

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

Rodriguez-Santiago, V; Fedkin, Mark V.; Lvov, Serguei N.

2012-01-01

Surface protonation reactions play an important role in the behavior of mineral and colloidal systems, specifically in hydrothermal aqueous environments. However, studies addressing the reactions at the solid/liquid interface at temperatures above 100 C are scarce. In this study, newly and previously obtained high temperature electrophoresis data (up to 260 C) zeta potentials and isoelectric points for metal oxides, including SiO2, SnO2, ZrO2, TiO2, and Fe3O4, were used in thermodynamic analysis to derive the standard enthalpies of their surface protonation. Two different approaches were used for calculating the protonation enthalpy: one is based on thermodynamic description of the 1-pKa modelmore » for surface protonation, and another one on a combination of crystal chemistry and solvation theories which link the relative permittivity of the solid phase and the ratio of the Pauling bond strength and bond length to standard protonation enthalpy. From this analysis, two expressions relating the protonation enthalpy to the relative permittivity of the solid phase were obtained.« less

Protonation enthalpies of metal oxides from high temperature electrophoresis.

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

Rodriguez-Santiago, V; Fedkin, Mark V; Lvov, Serguei N.

2012-01-01

Surface protonation reactions play an important role in the behavior of mineral and colloidal systems, specifically in hydrothermal aqueous environments. However, studies addressing the reactions at the solid/liquid interface at temperatures above 100 C are scarce. In this study, newly and previously obtained high temperature electrophoresis data (up to 260 C) - zeta potentials and isoelectric points - for metal oxides, including SiO{sub 2}, SnO{sub 2}, ZrO{sub 2}, TiO{sub 2}, and Fe{sub 3}O{sub 4}, were used in thermodynamic analysis to derive the standard enthalpies of their surface protonation. Two different approaches were used for calculating the protonation enthalpy: one ismore » based on thermodynamic description of the 1-pKa model for surface protonation, and another one - on a combination of crystal chemistry and solvation theories which link the relative permittivity of the solid phase and the ratio of the Pauling bond strength and bond length to standard protonation enthalpy. From this analysis, two expressions relating the protonation enthalpy to the relative permittivity of the solid phase were obtained.« less

Pressure-induced amorphization of a dense coordination polymer and its impact on proton conductivity

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

Umeyama, Daiki; Hagi, Keisuke; Ogiwara, Naoki

2014-12-01

The proton conductivity of a dense coordination polymer (CP) was investigated under high-pressure conditions. Impedance measurements under high pressures revealed that the proton conductivity of the CP decreased more than 1000-fold at pressures of 3–7 GPa and that the activation energy for proton conduction almost doubled compared with that at ambient pressure. A synchrotron X-ray study under high pressure identified the amorphization process of the CP during compression, which rationally explains the decrease in conductivity and increase in activation energy. This phenomenon is categorized as reversible pressure-induced amorphization of a dense CP and is regarded as a demonstration of themore » coupling of the mechanical and electrical properties of a CP.« less

Detection of spallation neutrons and protons using the (nat)Cd activation technique in transmutation experiments at Dubna.

PubMed

Manolopoulou, M; Stoulos, S; Fragopoulou, M; Brandt, R; Westmeier, W; Krivopustov, M; Sosnin, A; Zamani, M

2006-07-01

Various spallation sources have been used to transmute long-lived radioactive waste, mostly making use of the wide energy neutron fluence. In addition to neutrons, a large number of protons and gamma rays are also emitted from these sources. In this paper (nat)Cd is proved to be a useful activation detector for determining both thermal-epithermal neutron as well as secondary proton fluences. The fluences measured with (nat)Cd compared with other experimental data and calculations of DCM-DEM code were found to be in reasonable agreement. An accumulation of thermal-epithermal neutrons around the center of the target (i.e. after approx. 10 cm) and of secondary protons towards the end of the target is observed.

The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center

PubMed Central

Chung, Kwangzoo; Kim, Jinsung; Ahn, Sung Hwan; Ju, Sang Gyu; Jung, Sang Hoon; Chung, Yoonsun; Cho, Sungkoo; Jo, Kwanghyun; Shin, Eun Hyuk; Hong, Chae-Seon; Shin, Jung Suk; Park, Seyjoon; Kim, Dae-Hyun; Kim, Hye Young; Lee, Boram; Shibagaki, Gantaro; Nonaka, Hideki; Sasai, Kenzo; Koyabu, Yukio; Choi, Changhoon; Huh, Seung Jae; Ahn, Yong Chan; Pyo, Hong Ryull; Lim, Do Hoon; Park, Hee Chul; Park, Won; Oh, Dong Ryul; Noh, Jae Myung; Yu, Jeong Il; Song, Sanghyuk; Lee, Ji Eun; Lee, Bomi; Choi, Doo Ho

2015-01-01

Purpose The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. Materials and Methods The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. Results The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. Conclusion The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015. PMID:26756034

Activation of QA devices and phantom materials under clinical scanning proton beams—a gamma spectrometry study

NASA Astrophysics Data System (ADS)

Hanušová, Tereza; Johnová, Kamila; Navrátil, Matěj; Valenta, Jiří; Müller, Lutz

2018-06-01

Activation of detectors and phantoms used for commissioning and quality assurance of clinical proton beams may lead to radiation protection issues. Good understanding of the activation nuclide vectors involved is necessary to assess radiation risk for the personnel working with these devices on a daily basis or to fulfill legal requirements regarding transport of radioactive material and its release to the public. 11 devices and material samples were irradiated with a 220 MeV proton pencil beam (PBS, Proton Therapy Center, Prague). This study focuses on devices manufactured by IBA Dosimetry GmbH: MatriXX PT, PPC05, Stingray, Zebra, Lynx, a Blue Phantom rail and samples of RW3, PMMA, titanium, copper and carbon fibre plastic. Monitor units (MU) were monitored during delivery. Gamma spectrometry was then performed for each item using a HPGe detector, with a focus on longer lived gamma emitting radionuclides. Activities were quantified for all found isotopes and compared to relevant legal limits for exemption and clearance of radioactive objects. Activation was found to be significant after long irradiation sessions, as done during commissioning of a proton therapy room. Some of the investigated devices may also cumulate activity in time, depending on the scenario of periodic irradiation in routine clinical practice. However, the levels of activity and resulting beta/gamma doses are more comparable to internationally recommended concentration limits for exemption than to dose limits for radiation workers. Results of this study will help to determine nuclide inventories required by some legal authorities for radiation protection purposes.

Zn{sup 2+} induces apoptosis in human highly metastatic SHG-44 glioma cells, through inhibiting activity of the voltage-gated proton channel Hv1

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

Wang, Yifan; Zhang, Shangrong; Li, Shu Jie, E-mail: shujieli@nankai.edu.cn

Highlights: •Hv1 is expressed in highly metastatic glioma cell. •Zn{sup 2+} ions induces apoptosis in highly metastatic glioma cells. •Zn{sup 2+} ions markedly inhibit proton secretion. •Zn{sup 2+} ions reduce the gelatinase activity. •Inhibition of Hv1 activity via Zn{sup 2+} ions can effectively retard the cancer growth. -- Abstract: In contrast to the voltage-gated K{sup +} channels, the voltage-gated proton channel Hv1 contains a voltage-sensor domain but lacks a pore domain. Here, we showed that Hv1 is expressed in the highly metastatic glioma cell SHG-44, but lowly in the poorly metastatic glioma cell U-251. Inhibition of Hv1 activity by 140more » μM zinc chloride induces apoptosis in the human highly metastatic glioma cells. Zn{sup 2+} ions markedly inhibit proton secretion, and reduce the gelatinase activity in the highly metastatic glioma cells. In vivo, the glioma tumor sizes of the implantation of the SHG-44 xenografts in nude mice that were injected zinc chloride solution, were dramatically smaller than that in the controlled groups. The results demonstrated that the inhibition of Hv1 activity via Zn{sup 2+} ions can effectively retard the cancer growth and suppress the cancer metastasis by the decrease of proton extrusion and the down-regulation of gelatinase activity. Our results suggest that Zn{sup 2+} ions may be used as a potential anti-glioma drug for glioma therapy.« less

Activation of QA devices and phantom materials under clinical scanning proton beams-a gamma spectrometry study.

PubMed

Hanušová, Tereza; Johnová, Kamila; Navrátil, Matěj; Valenta, Jiří; Müller, Lutz

2018-06-07

Activation of detectors and phantoms used for commissioning and quality assurance of clinical proton beams may lead to radiation protection issues. Good understanding of the activation nuclide vectors involved is necessary to assess radiation risk for the personnel working with these devices on a daily basis or to fulfill legal requirements regarding transport of radioactive material and its release to the public. 11 devices and material samples were irradiated with a 220 MeV proton pencil beam (PBS, Proton Therapy Center, Prague). This study focuses on devices manufactured by IBA Dosimetry GmbH: MatriXX PT, PPC05, Stingray, Zebra, Lynx, a Blue Phantom rail and samples of RW3, PMMA, titanium, copper and carbon fibre plastic. Monitor units (MU) were monitored during delivery. Gamma spectrometry was then performed for each item using a HPGe detector, with a focus on longer lived gamma emitting radionuclides. Activities were quantified for all found isotopes and compared to relevant legal limits for exemption and clearance of radioactive objects. Activation was found to be significant after long irradiation sessions, as done during commissioning of a proton therapy room. Some of the investigated devices may also cumulate activity in time, depending on the scenario of periodic irradiation in routine clinical practice. However, the levels of activity and resulting beta/gamma doses are more comparable to internationally recommended concentration limits for exemption than to dose limits for radiation workers. Results of this study will help to determine nuclide inventories required by some legal authorities for radiation protection purposes.

Enhanced characterization of singly protonated phosphopeptide ions by femtosecond laser-induced ionization/dissociation tandem mass spectrometry (fs-LID-MS/MS).

PubMed

Smith, Scott A; Kalcic, Christine L; Safran, Kyle A; Stemmer, Paul M; Dantus, Marcos; Reid, Gavin E

2010-12-01

To develop an improved understanding of the regulatory role that post-translational modifications (PTMs) involving phosphorylation play in the maintenance of normal cellular function, tandem mass spectrometry (MS/MS) strategies coupled with ion activation techniques such as collision-induced dissociation (CID) and electron-transfer dissociation (ETD) are typically employed to identify the presence and site-specific locations of the phosphate moieties within a given phosphoprotein of interest. However, the ability of these techniques to obtain sufficient structural information for unambiguous phosphopeptide identification and characterization is highly dependent on the ion activation method employed and the properties of the precursor ion that is subjected to dissociation. Herein, we describe the application of a recently developed alternative ion activation technique for phosphopeptide analysis, termed femtosecond laser-induced ionization/dissociation (fs-LID). In contrast to CID and ETD, fs-LID is shown to be particularly suited to the analysis of singly protonated phosphopeptide ions, yielding a wide range of product ions including a, b, c, x, y, and z sequence ions, as well as ions that are potentially diagnostic of the positions of phosphorylation (e.g., 'a(n)+1-98'). Importantly, the lack of phosphate moiety losses or phosphate group 'scrambling' provides unambiguous information for sequence identification and phosphorylation site characterization. Therefore, fs-LID-MS/MS can serve as a complementary technique to established methodologies for phosphoproteomic analysis. Copyright © 2010. Published by Elsevier Inc.

Effect of protons on the mechanical response of rat muscle nociceptive fibers and neurons in vitro.

PubMed

Hotta, Norio; Kubo, Asako; Mizumura, Kazue

2015-03-01

Strong exercise makes muscle acidic, and painful. The stimulus that activates muscle nociceptors in such instance may be protons. Reportedly, however, not many afferents are excited by protons alone. We, therefore, posited that protons sensitize muscular nociceptors to mechanical stimuli. We examined effects of protons on mechanical sensitivity of muscle nociceptors by single-fiber recording from rat muscle-nerve preparations in vitro and by whole cell patch-clamp recording of mechanically activated (MA) currents from cultured rat dorsal root ganglion neurons. We recorded 38 Aδ- and C-fibers. Their response magnitude was increased by both pH 6.2 and pH 6.8; in addition the mechanical threshold was lowered by pH 6.2. Decrease in the threshold by pH6.2 was also observed in MA currents. Presently observed sensitization by protons could be involved in several types of ischemic muscle pain, and may also be involved in cardiovascular and respiratory controls during exercise. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Heteromerization of G2A and OGR1 enhances proton sensitivity and proton-induced calcium signals.

PubMed

Huang, Ya-Han; Su, Yeu-Shiuan; Chang, Chung-Jen; Sun, Wei-Hsin

2016-12-01

Proton-sensing G-protein-coupled receptors (GPCRs; OGR1, GPR4, G2A, TDAG8), with full activation at pH 6.4 ∼ 6.8, are important to pH homeostasis, immune responses and acid-induced pain. Although G2A mediates the G13-Rho pathway in response to acid, whether G2A activates Gs, Gi or Gq proteins remains debated. In this study, we examined the response of this fluorescence protein-tagged OGR1 family to acid stimulation in HEK293T cells. G2A did not generate detectable intracellular calcium or cAMP signals or show apparent receptor redistribution with moderate acid (pH ≥ 6.0) stimulation but reduced cAMP accumulation under strong acid stimulation (pH ≤ 5.5). Surprisingly, coexpression of OGR1- and G2A-enhanced proton sensitivity and proton-induced calcium signals. This alteration is attributed to oligomerization of OGR1 and G2A. The oligomeric potential locates receptors at a specific site, which leads to enhanced proton-induced calcium signals through channels.

Proton trapping in yttrium-doped barium zirconate

NASA Astrophysics Data System (ADS)

Yamazaki, Yoshihiro; Blanc, Frédéric; Okuyama, Yuji; Buannic, Lucienne; Lucio-Vega, Juan C.; Grey, Clare P.; Haile, Sossina M.

2013-07-01

The environmental benefits of fuel cells have been increasingly appreciated in recent years. Among candidate electrolytes for solid-oxide fuel cells, yttrium-doped barium zirconate has garnered attention because of its high proton conductivity, particularly in the intermediate-temperature region targeted for cost-effective solid-oxide fuel cell operation, and its excellent chemical stability. However, fundamental questions surrounding the defect chemistry and macroscopic proton transport mechanism of this material remain, especially in regard to the possible role of proton trapping. Here we show, through a combined thermogravimetric and a.c. impedance study, that macroscopic proton transport in yttrium-doped barium zirconate is limited by proton-dopant association (proton trapping). Protons must overcome the association energy, 29 kJ mol-1, as well as the general activation energy, 16 kJ mol-1, to achieve long-range transport. Proton nuclear magnetic resonance studies show the presence of two types of proton environment above room temperature, reflecting differences in proton-dopant configurations. This insight motivates efforts to identify suitable alternative dopants with reduced association energies as a route to higher conductivities.

Proton trapping in yttrium-doped barium zirconate.

PubMed

Yamazaki, Yoshihiro; Blanc, Frédéric; Okuyama, Yuji; Buannic, Lucienne; Lucio-Vega, Juan C; Grey, Clare P; Haile, Sossina M

2013-07-01

The environmental benefits of fuel cells have been increasingly appreciated in recent years. Among candidate electrolytes for solid-oxide fuel cells, yttrium-doped barium zirconate has garnered attention because of its high proton conductivity, particularly in the intermediate-temperature region targeted for cost-effective solid-oxide fuel cell operation, and its excellent chemical stability. However, fundamental questions surrounding the defect chemistry and macroscopic proton transport mechanism of this material remain, especially in regard to the possible role of proton trapping. Here we show, through a combined thermogravimetric and a.c. impedance study, that macroscopic proton transport in yttrium-doped barium zirconate is limited by proton-dopant association (proton trapping). Protons must overcome the association energy, 29 kJ mol(-1), as well as the general activation energy, 16 kJ mol(-1), to achieve long-range transport. Proton nuclear magnetic resonance studies show the presence of two types of proton environment above room temperature, reflecting differences in proton-dopant configurations. This insight motivates efforts to identify suitable alternative dopants with reduced association energies as a route to higher conductivities.

Reactivity of 12-tungstophosphoric acid and its inhibitor potency toward Na+/K+-ATPase: A combined 31P NMR study, ab initio calculations and crystallographic analysis.

PubMed

Bošnjaković-Pavlović, Nada; Bajuk-Bogdanović, Danica; Zakrzewska, Joanna; Yan, Zeyin; Holclajtner-Antunović, Ivanka; Gillet, Jean-Michel; Spasojević-de Biré, Anne

2017-11-01

Influence of 12-tungstophosphoric acid (WPA) on conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) in the presence of Na + /K + -ATPase was monitored by 31 P NMR spectroscopy. It was shown that WPA exhibits inhibitory effect on Na + /K + -ATPase activity. In order to study WPA reactivity and intermolecular interactions between WPA oxygen atoms and different proton donor types (D=O, N, C), we have considered data for WPA based compounds from the Cambridge Structural Database (CSD), the Crystallographic Open Database (COD) and the Inorganic Crystal Structure Database (ICSD). Binding properties of Keggin's anion in biological systems are illustrated using Protein Data Bank (PDB). This work constitutes the first determination of theoretical Bader charges on polyoxotungstate compound via the Atom In Molecule theory. An analysis of electrostatic potential maps at the molecular surface and charge of WPA, resulting from DFT calculations, suggests that the preferred protonation site corresponds to WPA bridging oxygen. These results enlightened WPA chemical reactivity and its potential biological applications such as the inhibition of the ATPase activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Carbinolamine Formation and Dehydration in a DNA Repair Enzyme Active Site

PubMed Central

Dodson, M. L.; Walker, Ross C.; Lloyd, R. Stephen

2012-01-01

In order to suggest detailed mechanistic hypotheses for the formation and dehydration of a key carbinolamine intermediate in the T4 pyrimidine dimer glycosylase (T4PDG) reaction, we have investigated these reactions using steered molecular dynamics with a coupled quantum mechanics–molecular mechanics potential (QM/MM). We carried out simulations of DNA abasic site carbinolamine formation with and without a water molecule restrained to remain within the active site quantum region. We recovered potentials of mean force (PMF) from thirty replicate reaction trajectories using Jarzynski averaging. We demonstrated feasible pathways involving water, as well as those independent of water participation. The water–independent enzyme–catalyzed reaction had a bias–corrected Jarzynski–average barrier height of approximately for the carbinolamine formation reaction and ) for the reverse reaction at this level of representation. When the proton transfer was facilitated with an intrinsic quantum water, the barrier height was approximately in the forward (formation) reaction and for the reverse. In addition, two modes of unsteered (free dynamics) carbinolamine dehydration were observed: in one, the quantum water participated as an intermediate proton transfer species, and in the other, the active site protonated glutamate hydrogen was directly transferred to the carbinolamine oxygen. Water–independent unforced proton transfer from the protonated active site glutamate carboxyl to the unprotonated N–terminal amine was also observed. In summary, complex proton transfer events, some involving water intermediates, were studied in QM/MM simulations of T4PDG bound to a DNA abasic site. Imine carbinolamine formation was characterized using steered QM/MM molecular dynamics. Dehydration of the carbinolamine intermediate to form the final imine product was observed in free, unsteered, QM/MM dynamics simulations, as was unforced acid-base transfer between the active site carboxylate and the N–terminal amine. PMID:22384015

Physical-chemical properties and the reactivity of pyridoxine and pyrrolidone carboxylate and their protolytic forms.

PubMed

Golovenko, N Ya; Larionov, V B; Karpova, O V

2016-01-01

Preparation Methadoxine is equimolar salt, which cationic component (pyridoxine) is 3-oxypyridine derivative, possessing B6-vitamine like activity, while anionic component is the cyclic lactame of glutamic acid. Since biopharmaceutical and pharmacological properties of this drug depend on biochemical transformation its components, of the aim of this work was to determine the structure of possible ionized pyridoxine and pyrrolidone carboxylate forms and their reaction ability in biochemical processes. Physical-chemical properties of compounds (pKa, logP, logD, proton donor/acceptor quantity, solubility (g/l)) were calculated with ACD/pKaDB program or obtained from Pub-Med physical/chemical properties database. UV spectra of compounds were obtained after dissolution in different pH solutions (1.0, 4.5 and 6.8). It was found that at different pH values one can observe changes of the absorption spectra due to the presence of prevailing amount of the protonated form. An analysis of both pKa, logP and logD indicators and reactive functional groups of Methadoxine components has revealed that they can be protonated in different regions of gastro-intestinal tract, that influences their solubility in hydrophilic and lypophilic media. Pharmacological properties of pyridoxine and pyrrolidone carboxylate themselves are performed after their preliminary biotransformation to active metabolites. Only ionic interaction between Methadoxine components in the substance composition can appear, that provides its pharmaceutical stability and ensures its activity only in the organism conditions.

The Vibrio cholerae Mrp system: cation/proton antiport properties and enhancement of bile salt resistance in a heterologous host.

PubMed

Dzioba-Winogrodzki, Judith; Winogrodzki, Olga; Krulwich, Terry A; Boin, Markus A; Häse, Claudia C; Dibrov, Pavel

2009-01-01

The mrp operon from Vibrio cholerae encoding a putative multisubunit Na(+)/H(+) antiporter was cloned and functionally expressed in the antiporter-deficient strain of Escherichia coli EP432. Cells of EP432 expressing Vc-Mrp exhibited resistance to Na(+) and Li(+) as well as to natural bile salts such as sodium cholate and taurocholate. When assayed in everted membrane vesicles of the E. coli EP432 host, Vc-Mrp had sufficiently high antiport activity to facilitate the first extensive analysis of Mrp system from a Gram-negative bacterium encoded by a group 2 mrp operon. Vc-Mrp was found to exchange protons for Li(+), Na(+), and K(+) ions in pH-dependent manner with maximal activity at pH 9.0-9.5. Exchange was electrogenic (more than one H(+) translocated per cation moved in opposite direction). The apparent K(m) at pH 9.0 was 1.08, 1.30, and 68.5 mM for Li(+), Na(+), and K(+), respectively. Kinetic analyses suggested that Vc-Mrp operates in a binding exchange mode with all cations and protons competing for binding to the antiporter. The robust ion antiport activity of Vc-Mrp in sub-bacterial vesicles and its effect on bile resistance of the heterologous host make Vc-Mrp an attractive experimental model for the further studies of biochemistry and physiology of Mrp systems. Copyright 2008 S. Karger AG, Basel.

Exploring the proton pump and exit pathway for pumped protons in cytochrome ba3 from Thermus thermophilus

PubMed Central

Chang, Hsin-Yang; Choi, Sylvia K.; Vakkasoglu, Ahmet Selim; Chen, Ying; Hemp, James; Fee, James A.; Gennis, Robert B.

2012-01-01

The heme-copper oxygen reductases are redox-driven proton pumps. In the current work, the effects of mutations in a proposed exit pathway for pumped protons are examined in the ba3-type oxygen reductase from Thermus thermophilus, leading from the propionates of heme a3 to the interface between subunits I and II. Recent studies have proposed important roles for His376 and Asp372, both of which are hydrogen-bonded to propionate-A of heme a3, and for Glu126II (subunit II), which is hydrogen-bonded to His376. Based on the current results, His376, Glu126II, and Asp372 are not essential for either oxidase activity or proton pumping. In addition, Tyr133, which is hydrogen-bonded to propionate-D of heme a3, was also shown not to be essential for function. However, two mutations of the residues hydrogen-bonded to propionate-A, Asp372Ile and His376Asn, retain high electron transfer activity and normal spectral features but, in different preparations, either do not pump protons or exhibit substantially diminished proton pumping. It is concluded that either propionate-A of heme a3 or possibly the cluster of groups centered about the conserved water molecule that hydrogen-bonds to both propionates-A and -D of heme a3 is a good candidate to be the proton loading site. PMID:22431640

Exploring the proton pump and exit pathway for pumped protons in cytochrome ba3 from Thermus thermophilus.

PubMed

Chang, Hsin-Yang; Choi, Sylvia K; Vakkasoglu, Ahmet Selim; Chen, Ying; Hemp, James; Fee, James A; Gennis, Robert B

2012-04-03

The heme-copper oxygen reductases are redox-driven proton pumps. In the current work, the effects of mutations in a proposed exit pathway for pumped protons are examined in the ba(3)-type oxygen reductase from Thermus thermophilus, leading from the propionates of heme a(3) to the interface between subunits I and II. Recent studies have proposed important roles for His376 and Asp372, both of which are hydrogen-bonded to propionate-A of heme a(3), and for Glu126(II) (subunit II), which is hydrogen-bonded to His376. Based on the current results, His376, Glu126(II), and Asp372 are not essential for either oxidase activity or proton pumping. In addition, Tyr133, which is hydrogen-bonded to propionate-D of heme a(3), was also shown not to be essential for function. However, two mutations of the residues hydrogen-bonded to propionate-A, Asp372Ile and His376Asn, retain high electron transfer activity and normal spectral features but, in different preparations, either do not pump protons or exhibit substantially diminished proton pumping. It is concluded that either propionate-A of heme a(3) or possibly the cluster of groups centered about the conserved water molecule that hydrogen-bonds to both propionates-A and -D of heme a(3) is a good candidate to be the proton loading site.

Stochastic acidification, activation of hemagglutinin and escape of influenza viruses from an endosome

NASA Astrophysics Data System (ADS)

Lagache, Thibault; Sieben, Christian; Meyer, Tim; Herrmann, Andreas; Holcman, David

2017-06-01

Influenza viruses enter the cell inside an endosome. During the endosomal journey, acidification triggers a conformational change of the virus spike protein hemagglutinin (HA) that results in escape of the viral genome from the endosome into the cytoplasm. It is still unclear how the interplay between acidification and HA conformation changes affects the kinetics of the viral endosomal escape. We develop here a stochastic model to estimate the change of conformation of HAs inside the endosome nanodomain. Using a Markov process, we model the arrival of protons to HA binding sites and compute the kinetics of their accumulation. We compute the Mean First Passage Time (MFPT) of the number of HA bound sites to a threshold, which is used to estimate the HA activation rate for a given pH concentration. The present analysis reveals that HA proton binding sites possess a high chemical barrier, ensuring a stability of the spike protein at sub-acidic pH. We predict that activating more than 3 adjacent HAs is necessary to trigger endosomal fusion and this configuration prevents premature release of viruses from early endosomes

Di/mono-nuclear iron(I)/(II) complexes as functional models for the 2Fe2S subunit and distal Fe moiety of the active site of [FeFe] hydrogenases: protonations, molecular structures and electrochemical properties.

PubMed

Gao, Shang; Fan, Jiangli; Sun, Shiguo; Song, Fengling; Peng, Xiaojun; Duan, Qian; Jiang, Dayong; Liang, Qingcheng

2012-10-21

Di/mono-nuclear iron(I)/(II) complexes containing conjugated and electron-withdrawing S-to-S linkers, [{(μ-S)(2)(C(4)N(2)H(2))}Fe(2)(CO)(6)] (1), [{(μ-S)(2)(C(4)N(2)H(2))}Fe(2)(CO)(5)(PMe(3))] (1P), and [{(μ-S)(2)(C(4)N(2)H(2))}Fe(CO)(2)(PMe(3))(2)] (2) were prepared as biomimetic models for the 2Fe2S subunit and distal Fe moiety of the active site of [FeFe] hydrogenases. The N atoms in the heterocyclic pyrazines of 1 and 2 were protonated in the presence of proton acid to generate one and two hydrides, [1(NH)](+) CF(3)SO(3)(-), [2(NH)](+) CF(3)SO(3)(-), and [2(NH)(2)](2+) (CF(3)SO(3)(-))(2), respectively. The protonation processes were evidenced by in situ IR and NMR spectroscopy. The molecular structures of the protonated species [1(NH)](+) CF(3)SO(3)(-) and [2(NH)(2)](2+) (CF(3)SO(3)(-))(2) together with their originating complexes and , and the mono-PMe(3) substituted diiron complex were identified by X-ray crystallography. The IR and single-crystal analysis data all suggested that the electron-withdrawing bridge, pyrazine, led to decreased electron density at the Fe centers of the model complexes, which was consistent with the electrochemical studies. The cyclic voltammograms indicated that complex exhibited a low primary reduction potential at -1.17 V vs. Fc-Fc(+) with a 270 mV positive shift compared with that of the benzene-1,2-dithiolate (bdt) bridged analogue [(μ-bdt)Fe(2)(CO)(6)]. Under the weak acid conditions, complexes 1 and 2 could electrochemically catalyze the proton reduction. More interestingly, the mononuclear ferrous complex 2 showed two catalytic peaks during the formation of hydrogen, confirming its potential as a catalyst for hydrogen production.

How vertebrate and invertebrate visual pigments differ in their mechanism of photoactivation

PubMed Central

Nakagawa, Masashi; Iwasa, Tatsuo; Kikkawa, Satoshi; Tsuda, Motoyuki; Ebrey, Thomas G.

1999-01-01

In vertebrate visual pigments, a glutamic acid serves as a negative counterion to the positively charged chromophore, a protonated Schiff base of retinal. When photoisomerization leads to the Schiff base deprotonating, the anionic glutamic acid becomes protonated, forming a neutral species that activates the visual cascade. We show that in octopus rhodopsin, the glutamic acid has no anionic counterpart. Thus, the “counterion” is already neutral, so no protonated form of an initially anionic group needs to be created to activate. This helps to explain another observation—that the active photoproduct of octopus rhodopsin can be formed without its Schiff base deprotonating. In this sense, the mechanism of light activation of octopus rhodopsin is simpler than for vertebrates, because it eliminates one of the steps required for vertebrate rhodopsins to achieve their activating state. PMID:10339563

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.

Quasi-monoenergetic proton beam from a proton-layer embedded metal foil irradiated by an intense laser pulse

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

Kim, Kyung Nam; Lee, Kitae, E-mail: klee@kaeri.re.kr; Kumar, Manoj

A target structure, ion-layer embedded foil (ILEF) is proposed for producing a quasi-monoenergetic proton beam by utilizing a bulk electrostatic field, which is generated by irradiating the target with an ultra-intense laser pulse, inside the plasma. Compared with the case of a single metal foil in which the proton layer is initially present on the surface, in the ILEF target, the proton layer is initially located inside a metal foil. A two-dimensional particle-in-cell (PIC) simulation shows that the target generates a proton beam with a narrow energy spread. With a laser intensity of 2 × 10{sup 19 }W/cm{sup 2}, a 22-MeV proton beammore » with an energy spread of 8% at the full-width-half-maximum (FWHM) is obtained when the proton layer is located at 0.4 μm inside the rear surface of a 2.4 μm-thick copper foil. When the proton layer moves toward the front side, a proton beam with a flat-top energy distribution ranging from 15 MeV to 35 MeV is obtained. Further, with a higher laser intensity of 10{sup 21 }W/cm{sup 2}, a proton beam with the maximum energy of 345 MeV and FWHM energy spread of 7.2% is obtained. The analysis of the PIC simulation with an aid of a fluid analysis shows that the spectrum is affected by the initial position of the proton layer, its initial spread during the formation of the sheath field, and the space charge effect.« less

Can membrane-bound carotenoid pigment zeaxanthin carry out a transmembrane proton transfer?

PubMed

Kupisz, Kamila; Sujak, Agnieszka; Patyra, Magdalena; Trebacz, Kazimierz; Gruszecki, Wiesław I

2008-10-01

Polar carotenoid pigment zeaxanthin (beta,beta-carotene-3,3'-diol) incorporated into planar lipid membranes formed with diphytanoyl phosphatidylcholine increases the specific electric resistance of the membrane from ca. 4 to 13 x 10(7) Omega cm2 (at 5 mol% zeaxanthin with respect to lipid). Such an observation is consistent with the well known effect of polar carotenoids in decreasing fluidity and structural stabilization of lipid bilayers. Zeaxanthin incorporated into the lipid membrane at 1 mol% has very small effect on the overall membrane resistance but facilitates equilibration of the transmembrane proton gradient, as demonstrated with the application of the H+-sensitive antimony electrodes. Relatively low changes in the electrical potential suggest that the equilibration process may be associated with a symport/antiport activity or with a transmembrane transfer of the molecules of acid. UV-Vis linear dichroism analysis of multibilayer formed with the same lipid-carotenoid system shows that the transition dipole moment of the pigment molecules forms a mean angle of 21 degrees with respect to the axis normal to the plane of the membrane. This means that zeaxanthin spans the membrane and tends to have its two hydroxyl groups anchored in the opposite polar zones of the membrane. Detailed FTIR analysis of beta-carotene and zeaxanthin indicates that the polyene chain of carotenoids is able to form weak hydrogen bonds with water molecules. Possible molecular mechanisms responsible for proton transport by polyenes are discussed, including direct involvement of the polyene chain in proton transfer and indirect effect of the pigment on physical properties of the membrane.

Homogenous Electrocatalytic Oxygen Reduction Rates Correlate with Reaction Overpotential in Acidic Organic Solutions

PubMed Central

2016-01-01

Improved electrocatalysts for the oxygen reduction reaction (ORR) are critical for the advancement of fuel cell technologies. Herein, we report a series of 11 soluble iron porphyrin ORR electrocatalysts that possess turnover frequencies (TOFs) from 3 s–1 to an unprecedented value of 2.2 × 106 s–1. These TOFs correlate with the ORR overpotential, which can be modulated by changing the E1/2 of the catalyst using different ancillary ligands, by changing the solvent and solution acidity, and by changing the catalyst’s protonation state. The overpotential is well-defined for these homogeneous electrocatalysts by the E1/2 of the catalyst and the proton activity of the solution. This is the first such correlation for homogeneous ORR electrocatalysis, and it demonstrates that the remarkably fast TOFs are a consequence of high overpotential. The correlation with overpotential is surprising since the turnover limiting steps involve oxygen binding and protonation, as opposed to turnover limiting electron transfer commonly found in Tafel analysis of heterogeneous ORR materials. Computational studies show that the free energies for oxygen binding to the catalyst and for protonation of the superoxide complex are in general linearly related to the catalyst E1/2, and that this is the origin of the overpotential correlations. This analysis thus provides detailed understanding of the ORR barriers. The best catalysts involve partial decoupling of the influence of the second coordination sphere from the properties of the metal center, which is suggested as new molecular design strategy to avoid the limitations of the traditional scaling relationships for these catalysts. PMID:27924314

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.

Blackbody infrared radiative dissociation of bradykinin and its analogues: energetics, dynamics, and evidence for salt-bridge structures in the gas phase.

PubMed

Schnier, P D; Price, W D; Jockusch, R A; Williams, E R

1996-07-31

Blackbody infrared radiative dissociation (BIRD) spectra of singly and doubly protonated bradykinin and its analogues are measured in a Fourier-transform mass spectrometer. Rate constants for dissociation are measured as a function of temperature with reaction delays up to 600 s. From these data, Arrhenius activation parameters in the zero-pressure limit are obtained. The activation parameters and dissociation products for the singly protonated ions are highly sensitive to small changes in ion structure. The Arrhenius activation energy (E(a)) and pre-exponential (or frequency factor, A) of the singly protonated ions investigated here range from 0.6 to 1.4 eV and 10(5) to 10(12) s(-1), respectively. For bradykinin and its analogues differing by modification of the residues between the two arginine groups on either end of the molecule, the singly and doubly protonated ions have average activation energies of 1.2 and 0.8 eV, respectively, and average A values of 10(8) and 10(12) s(-1), respectively, i.e., the presence of a second charge reduces the activation energy by 0.4 eV and decreases the A value by a factor of 10(4). This demonstrates that the presence of a second charge can dramatically influence the dissociation dynamics of these ions. The doubly protonated methyl ester of bradykinin has an E(a) of 0.82 eV, comparable to the value of 0.84 eV for bradykinin itself. However, this value is 0.21 +/- 0.08 eV greater than that of singly protonated methyl ester of bradykinin, indicating that the Coulomb repulsion is not the most significant factor in the activation energy of this ion. Both singly and doubly protonated Lys-bradykinin ions have higher activation energies than the corresponding bradykinin ions indicating that the addition of a basic residue stabilizes these ions with respect to dissociation. Methylation of the carboxylic acid group of the C-terminus reduces the E(a) of bradykinin from 1.3 to 0.6 eV and the A factor from 1012 to 105 s(-1). This modification also dramatically changes the dissociation products. Similar results are observed for [Ala(6)]-bradykinin and its methyl ester. These results, in combination with others presented here, provide experimental evidence that the most stable form of singly protonated bradykinin is a salt-bridge structure.

Stability of proton-bound clusters of alkyl alcohols, aldehydes and ketones in Ion Mobility Spectrometry.

PubMed

Jurado-Campos, Natividad; Garrido-Delgado, Rocío; Martínez-Haya, Bruno; Eiceman, Gary A; Arce, Lourdes

2018-08-01

Significant substances in emerging applications of ion mobility spectrometry such as breath analysis for clinical diagnostics and headspace analysis for food purity include low molar mass alcohols, ketones, aldehydes and esters which produce mobility spectra containing protonated monomers and proton-bound dimers. Spectra for all n- alcohols, aldehydes and ketones from carbon number three to eight exhibited protonated monomers and proton-bound dimers with ion drift times of 6.5-13.3 ms at ambient pressure and from 35° to 80 °C in nitrogen. Only n-alcohols from 1-pentanol to 1-octanol produced proton-bound trimers which were sufficiently stable to be observed at these temperatures and drift times of 12.8-16.3 ms. Polar functional groups were protected in compact structures in ab initio models for proton-bound dimers of alcohols, ketones and aldehydes. Only alcohols formed a V-shaped arrangement for proton-bound trimers strengthening ion stability and lifetime. In contrast, models for proton-bound trimers of aldehydes and ketones showed association of the third neutral through weak, non-specific, long-range interactions consistent with ion dissociation in the ion mobility drift tube before arriving at the detector. Collision cross sections derived from reduced mobility coefficients in nitrogen gas atmosphere support the predicted ion structures and approximate degrees of hydration. Copyright © 2018 Elsevier B.V. All rights reserved.

AlkB Dioxygenase Preferentially Repairs Protonated Substrates

PubMed Central

Maciejewska, Agnieszka M.; Poznański, Jarosław; Kaczmarska, Zuzanna; Krowisz, Beata; Nieminuszczy, Jadwiga; Polkowska-Nowakowska, Agnieszka; Grzesiuk, Elżbieta; Kuśmierek, Jarosław T.

2013-01-01

Efficient repair by Escherichia coli AlkB dioxygenase of exocyclic DNA adducts 3,N4-ethenocytosine, 1,N6-ethenoadenine, 3,N4-α-hydroxyethanocytosine, and reported here for the first time 3,N4-α-hydroxypropanocytosine requires higher Fe(II) concentration than the reference 3-methylcytosine. The pH optimum for the repair follows the order of pKa values for protonation of the adduct, suggesting that positively charged substrates favorably interact with the negatively charged carboxylic group of Asp-135 side chain in the enzyme active center. This interaction is supported by molecular modeling, indicating that 1,N6-ethenoadenine and 3,N4-ethenocytosine are bound to AlkB more favorably in their protonated cationic forms. An analysis of the pattern of intermolecular interactions that stabilize the location of the ligand points to a role of Asp-135 in recognition of the adduct in its protonated form. Moreover, ab initio calculations also underline the role of substrate protonation in lowering the free energy barrier of the transition state of epoxidation of the etheno adducts studied. The observed time courses of repair of mixtures of stereoisomers of 3,N4-α-hydroxyethanocytosine or 3,N4-α-hydroxypropanocytosine are unequivocally two-exponential curves, indicating that the respective isomers are repaired by AlkB with different efficiencies. Molecular modeling of these adducts bound by AlkB allowed evaluation of the participation of their possible conformational states in the enzymatic reaction. PMID:23148216

Extraction of the proton radius from electron-proton scattering data

DOE PAGES

Lee, Gabriel; Arrington, John R.; Hill, Richard J.

2015-07-27

We perform a new analysis of electron-proton scattering data to determine the proton electric and magnetic radii, enforcing model-independent constraints from form factor analyticity. A wide-ranging study of possible systematic effects is performed. An improved analysis is developed that rebins data taken at identical kinematic settings and avoids a scaling assumption of systematic errors with statistical errors. Employing standard models for radiative corrections, our improved analysis of the 2010 Mainz A1 Collaboration data yields a proton electric radius r E = 0.895(20) fm and magnetic radius r M = 0.776(38) fm. A similar analysis applied to world data (excluding Mainzmore » data) implies r E = 0.916(24) fm and r M = 0.914(35) fm. The Mainz and world values of the charge radius are consistent, and a simple combination yields a value r E = 0.904(15) fm that is 4σ larger than the CREMA Collaboration muonic hydrogen determination. The Mainz and world values of the magnetic radius differ by 2.7σ, and a simple average yields r M = 0.851(26) fm. As a result, the circumstances under which published muonic hydrogen and electron scattering data could be reconciled are discussed, including a possible deficiency in the standard radiative correction model which requires further analysis.« less

Currents through Hv1 channels deplete protons in their vicinity.

PubMed

De-la-Rosa, Víctor; Suárez-Delgado, Esteban; Rangel-Yescas, Gisela E; Islas, León D

2016-02-01

Proton channels have evolved to provide a pH regulatory mechanism, affording the extrusion of protons from the cytoplasm at all membrane potentials. Previous evidence has suggested that channel-mediated acid extrusion could significantly change the local concentration of protons in the vicinity of the channel. In this work, we directly measure the proton depletion caused by activation of Hv1 proton channels using patch-clamp fluorometry recordings from channels labeled with the Venus fluorescent protein at intracellular domains. The fluorescence of the Venus protein is very sensitive to pH, thus behaving as a genetically encoded sensor of local pH. Eliciting outward proton currents increases the fluorescence intensity of Venus. This dequenching is related to the magnitude of the current and not to channel gating and is dependent on the pH gradient. Our results provide direct evidence of local proton depletion caused by flux through the proton-selective channel. © 2016 De-la-Rosa et al.

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

Functional rotation induced by alternating protonation states in the multidrug transporter AcrB: all-atom molecular dynamics simulations.

PubMed

Yamane, Tsutomu; Murakami, Satoshi; Ikeguchi, Mitsunori

2013-10-29

The multidrug transporter AcrB actively exports a wide variety of noxious compounds using proton-motive force as an energy source in Gram-negative bacteria. AcrB adopts an asymmetric structure comprising three protomers with different conformations that are sequentially converted during drug export; these cyclic conformational changes during drug export are referred to as functional rotation. To investigate functional rotation driven by proton-motive force, all-atom molecular dynamics simulations were performed. Using different protonation states for the titratable residues in the middle of the transmembrane domain, our simulations revealed the correlation between the specific protonation states and the side-chain configurations. Changing the protonation state for Asp408 induced a spontaneous structural transition, which suggests that the proton translocation stoichiometry may be one proton per functional rotation cycle. Furthermore, our simulations demonstrate that alternating the protonation states in the transmembrane domain induces functional rotation in the porter domain, which is primarily responsible for drug transport.

High-Accuracy Analysis of Compton Scattering in Chiral EFT: Proton and Neutron Polarisabilities

NASA Astrophysics Data System (ADS)

Griesshammer, Harald W.; Phillips, Daniel R.; McGovern, Judith A.

2013-10-01

Compton scattering from protons and neutrons provides important insight into the structure of the nucleon. A new extraction of the static electric and magnetic dipole polarisabilities αE 1 and βM 1 of the proton and neutron from all published elastic data below 300 MeV in Chiral Effective Field Theory shows that within the statistics-dominated errors, the proton and neutron polarisabilities are identical, i.e. no iso-spin breaking effects of the pion cloud are seen. Particular attention is paid to the precision and accuracy of each data set, and to an estimate of residual theoretical uncertainties. ChiEFT is ideal for that purpose since it provides a model-independent estimate of higher-order corrections and encodes the correct low-energy dynamics of QCD, including, for few-nucleon systems used to extract neutron polarisabilities, consistent nuclear currents, rescattering effects and wave functions. It therefore automatically respects the low-energy theorems for photon-nucleus scattering. The Δ (1232) as active degree of freedom is essential to realise the full power of the world's Compton data.Its parameters are constrained in the resonance region. A brief outlook is provided on what kind of future experiments can improve the database. Supported in part by UK STFC, DOE, NSF, and the Sino-German CRC 110.

Protons stabilize the closed conformation of gain-of-function mutants of the TRPV1 channel.

PubMed

Boukalova, Stepana; Teisinger, Jan; Vlachova, Viktorie

2013-03-01

The vanilloid transient receptor potential channel TRPV1 is a molecular integrator of noxious stimuli, including capsaicin, heat and protons. Despite clear similarities between the overall architecture of TRPV1 and voltage-dependent potassium (Kv) channels, the extent of conservation in the molecular logic for gating is unknown. In Kv channels, a small contact surface between S1 and the pore-helix is required for channel functioning. To explore the function of S1 in TRPV1, we used tryptophan-scanning mutagenesis and characterized the responses to capsaicin and protons. Wild-type-like currents were generated in 9 out of 17 mutants; three mutants (M445W, A452W, R455W) were non-functional. The conservative mutation R455K in the extracellular extent of S1 slowed down capsaicin-induced activation and prevented normal channel closure. This mutant was neither activated nor potentiated by protons, on the contrary, protons promoted a rapid deactivation of its currents. Similar phenotypes were found in two other gain-of-function mutants and also in the pore-helix mutant T633A, known to uncouple proton activation. We propose that the S1 domain contains a functionally important region that may be specifically involved in TRPV1 channel gating, and thus be important for the energetic coupling between S1-S4 sensor activation and gate opening. Analogous to Kv channels, the S1-pore interface might serve to stabilize conformations associated with TRPV1 channel gating. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose-volume histogram analysis.

PubMed

Makishima, Hirokazu; Ishikawa, Hitoshi; Terunuma, Toshiyuki; Hashimoto, Takayuki; Yamanashi, Koichi; Sekiguchi, Takao; Mizumoto, Masashi; Okumura, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

2015-05-01

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose-volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5-V20, mean lung dose (MLD), and heart V30-V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Analysis of Deactivation Mechanism on a Multi-Component Sulfur-Tolerant Steam Reforming Catalyst

DTIC Science & Technology

2010-08-01

Alkaline Fuel Cells (AFC) .............................................................................. 4 1.1.2. Proton Exchange Membrane Fuel Cells ( PEMFC ...temperature fuel cells. Alkaline Fuel Cell (AFC), Proton Exchange Membrane Fuel Cell ( PEMFC ), DMFC and Phosphoric Acid Fuel Cell (PAFC) are low...1960s. 1.1.2. Proton Exchange Membrane Fuel Cells ( PEMFC ) Proton exchange membrane fuel cells are said to be the best type of fuel cells to replace

Quantitative chemical exchange saturation transfer (qCEST) MRI - omega plot analysis of RF-spillover-corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate.

PubMed

Wu, Renhua; Xiao, Gang; Zhou, Iris Yuwen; Ran, Chongzhao; Sun, Phillip Zhe

2015-03-01

Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST-weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P < 0.01) while the pH-dependent exchange rate followed a dominantly base-catalyzed exchange relationship (P < 0.01). In summary, our study verified that a simplified qCEST analysis can simultaneously determine labile proton ratio and exchange rate in a relatively complex in vitro CEST system. Copyright © 2015 John Wiley & Sons, Ltd.

Protonic transport through solitons in hydrogen-bonded systems

NASA Astrophysics Data System (ADS)

Kavitha, L.; Jayanthi, S.; Muniyappan, A.; Gopi, D.

2011-09-01

We offer an alternative route for investigating soliton solutions in hydrogen-bonded (HB) chains. We invoke the modified extended tangent hyperbolic function method coupled with symbolic computation to solve the governing equation of motion for proton dynamics. We investigate the dynamics of proton transfer in HB chains through bell-shaped soliton excitations, which trigger the bio-energy transport in most biological systems. This solitonic mechanism of proton transfer could play functional roles in muscular contraction, enzymatic activity and oxidative phosphorylation.

Angular analysis of the decay B$^+$$\\to$$ K$$^+\\mu^+\\mu^-$$ in proton-proton collisions at $$\\sqrt{s} =$$ 8 TeV

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

Sirunyan, Albert M; et al.

The angular distribution of the flavor-changing neutral current decay Bmore » $^+$$\\to$$ K$$^+\\mu^+\\mu^-$$ is studied in proton-proton collisions at a center-of-mass energy of 8 TeV. The analysis is based on data collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 20.5 fb$$^{-1}$$. The forward-backward asymmetry $$A_{\\mathrm{FB}}$$ of the dimuon system and the contribution $$F_{\\mathrm{H}}$$ from the pseudoscalar, scalar, and tensor amplitudes to the decay width are measured as a function of the dimuon mass squared. The measurements are consistent with the standard model expectations.« less

A graphene-based physiometer array for the analysis of single biological cells

NASA Astrophysics Data System (ADS)

Paulus, Geraldine L. C.; Nelson, Justin T.; Lee, Katherine Y.; Wang, Qing Hua; Reuel, Nigel F.; Grassbaugh, Brittany R.; Kruss, Sebastian; Landry, Markita P.; Kang, Jeon Woong; Vander Ende, Emma; Zhang, Jingqing; Mu, Bin; Dasari, Ramachandra R.; Opel, Cary F.; Wittrup, K. Dane; Strano, Michael S.

2014-10-01

A significant advantage of a graphene biosensor is that it inherently represents a continuum of independent and aligned sensor-units. We demonstrate a nanoscale version of a micro-physiometer - a device that measures cellular metabolic activity from the local acidification rate. Graphene functions as a matrix of independent pH sensors enabling subcellular detection of proton excretion. Raman spectroscopy shows that aqueous protons p-dope graphene - in agreement with established doping trajectories, and that graphene displays two distinct pKa values (2.9 and 14.2), corresponding to dopants physi- and chemisorbing to graphene respectively. The graphene physiometer allows micron spatial resolution and can differentiate immunoglobulin (IgG)-producing human embryonic kidney (HEK) cells from non-IgG-producing control cells. Population-based analyses allow mapping of phenotypic diversity, variances in metabolic activity, and cellular adhesion. Finally we show this platform can be extended to the detection of other analytes, e.g. dopamine. This work motivates the application of graphene as a unique biosensor for (sub)cellular interrogation.

Positive Feedback Amplifies the Response of Mitochondrial Membrane Potential to Glucose Concentration in Clonal Pancreatic Beta Cells

PubMed Central

GERENCSER, Akos A.; MOOKERJEE, Shona A.; JASTROCH, Martin; BRAND, Martin D.

2016-01-01

Analysis of the cellular mechanisms of metabolic disorders, including type 2 diabetes mellitus, is complicated by the large number of reactions and interactions in metabolic networks. Metabolic control analysis with appropriate modularization is a powerful method for simplifying and analyzing these networks. To analyze control of cellular energy metabolism in adherent cell cultures of the INS-1 832/13 pancreatic β-cell model we adapted our microscopy assay of absolute mitochondrial membrane potential (ΔψM) to a fluorescence microplate reader format, and applied it in conjunction with cell respirometry. In these cells the sensitive response of ΔψM to extracellular glucose concentration drives glucose-stimulated insulin secretion. Using metabolic control analysis we identified the control properties that generate this sensitive response. Force-flux relationships between ΔψM and respiration were used to calculate kinetic responses to ΔψM of processes both upstream (glucose oxidation) and downstream (proton leak and ATP turnover) of ΔψM. The analysis revealed that glucose-evoked ΔψM hyperpolarization is amplified by increased glucose oxidation activity caused by factors downstream of ΔψM. At high glucose, the hyperpolarized ΔψM is stabilized almost completely by the action of glucose oxidation, whereas proton leak also contribute to the homeostatic control of ΔψM at low glucose. These findings suggest a strong positive feedback loop in the regulation of β-cell energetics, and a possible regulatory role of proton leak in the fasting state. Analysis of islet bioenergetics from published cases of type 2 diabetes suggests that disruption of this feedback can explain the damaged bioenergetic response of β-cells to glucose. PMID:27771512

Consequences of Relativistic Neutron Outflow beyond the Accretion Disks of Active Galaxies

NASA Astrophysics Data System (ADS)

Ekejiuba, I. E.; Okeke, P. N.

1993-05-01

Three channels of relativistic electron injection in the jets of extragalactic radio sources (EGRSs) are discussed. With the assumption that an active galactic nucleus (AGN) is powered by a spinning supermassive black hole of mass ~ 10(8) M_⊙ which sits at the center of the nucleus and ingests matter and energy through an accretion disk, a model for extracting relativistic neutrons from the AGN is forged. In this model, the inelastic proton--proton and proton--photon interactions within the accretion disk, of relativistic protons with background thermal protons and photons, respectively, produce copious amounts of relativistic neutrons. These neutrons travel ballistically for ~ 10(3gamma_n ) seconds and escape from the disk before they decay. The secondary particles produced from the neutron decays then interact with the ambient magnetic field and/or other particles to produce the radio emissions observed in the jets of EGRSs. IEE acknowledges the support of the World Bank and the Federal University of Technology, Yola, Nigeria as well as the hospitality of Georgia State University.

EPR/alanine dosimetry for two therapeutic proton beams

NASA Astrophysics Data System (ADS)

Marrale, Maurizio; Carlino, Antonio; Gallo, Salvatore; Longo, Anna; Panzeca, Salvatore; Bolsi, Alessandra; Hrbacek, Jan; Lomax, Tony

2016-02-01

In this work the analysis of the electron paramagnetic resonance (EPR) response of alanine pellets exposed to two different clinical proton beams employed for radiotherapy is performed. One beam is characterized by a passive delivery technique and is dedicated to the eyes treatment (OPTIS2 beam line). Alanine pellets were irradiated with a 70 MeV proton beam corresponding to 35 mm range in eye tissue. We investigated how collimators with different sizes and shape used to conform the dose to the planned target volume influence the delivered dose. For this purpose we performed measurements with varying the collimator size (Output Factor) and the results were compared with those obtained with other dosimetric techniques (such as Markus chamber and diode detector). This analysis showed that the dosimeter response is independent of collimator diameter if this is larger than or equal to 10 mm. The other beam is characterized by an active spot-scanning technique, the Gantry1 beam line (maximum energy 230 MeV), and is used to treat deep-seated tumors. The dose linearity of alanine response in the clinical dose range was tested and the alanine dose response at selected locations in depth was measured and compared with the TPS planned dose in a quasi-clinical scenario. The alanine response was found to be linear in the dose in the clinical explored range (from 10 to 70 Gy). Furthermore, a depth dose profile in a quasi-clinical scenario was measured and compared to the dose computed by the Treatment Planning System PSIPLAN. The comparison of calibrated proton alanine measurements and TPS dose shows a difference under 1% in the SOBP and a "quenching" effect up to 4% in the distal part of SOBP. The positive dosimetric characteristics of the alanine pellets confirm the feasibility to use these detectors for "in vivo" dosimetry in clinical proton beams.

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.

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.

Transformation of [M + 2H](2+) Peptide Cations to [M - H](+), [M + H + O](+), and M(+•) Cations via Ion/Ion Reactions: Reagent Anions Derived from Persulfate.

PubMed

Pilo, Alice L; Bu, Jiexun; McLuckey, Scott A

2015-07-01

The gas-phase oxidation of doubly protonated peptides is demonstrated here using ion/ion reactions with a suite of reagents derived from persulfate. Intact persulfate anion (HS2O8(-)), peroxymonosulfate anion (HSO5(-)), and sulfate radical anion (SO4(-•)) are all either observed directly upon negative nanoelectrospray ionization (nESI) or easily obtained via beam-type collisional activation of persulfate into the mass spectrometer. Ion/ion reactions between each of these reagents and doubly protonated peptides result in the formation of a long-lived complex. Collisional activation of the complex containing a peroxymonosulfate anion results in oxygen transfer from the reagent to the peptide to generate the [M + H + O](+) species. Activation of the complex containing intact persulfate anion either results in oxygen transfer to generate the [M + H + O](+) species or abstraction of two hydrogen atoms and a proton to generate the [M - H](+) species. Activation of the complex containing sulfate radical anion results in abstraction of one hydrogen atom and a proton to form the peptide radical cation, [M](+•). This suite of reagents allows for the facile transformation of the multiply protonated peptides obtained via nESI into a variety of oxidized species capable of providing complementary information about the sequence and structure of the peptide.

Peroxide Activation for Electrophilic Reactivity by the Binuclear Non-heme Iron Enzyme AurF

DOE PAGES

Park, Kiyoung; Li, Ning; Kwak, Yeonju; ...

2017-05-01

Binuclear non-heme iron enzymes activate O 2 for diverse chemistries that include oxygenation of organic substrates and hydrogen atom abstraction. This process often involves the formation of peroxo-bridged biferric intermediates, only some of which can perform electrophilic reactions. To elucidate the geometric and electronic structural requirements to activate peroxo reactivity, the active peroxo intermediate in 4-aminobenzoate N-oxygenase (AurF) has been characterized spectroscopically and computationally. A magnetic circular dichroism study of reduced AurF shows that its electronic and geometric structures are poised to react rapidly with O 2. Nuclear resonance vibrational spectroscopic definition of the peroxo intermediate formed in this reactionmore » shows that the active intermediate has a protonated peroxo bridge. Density functional theory computations on the structure established here show that the protonation activates peroxide for electrophilic/single-electron-transfer reactivity. As a result, this activation of peroxide by protonation is likely also relevant to the reactive peroxo intermediates in other binuclear non-heme iron enzymes.« less

Peroxide Activation for Electrophilic Reactivity by the Binuclear Non-heme Iron Enzyme AurF

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

Park, Kiyoung; Li, Ning; Kwak, Yeonju

Binuclear non-heme iron enzymes activate O 2 for diverse chemistries that include oxygenation of organic substrates and hydrogen atom abstraction. This process often involves the formation of peroxo-bridged biferric intermediates, only some of which can perform electrophilic reactions. To elucidate the geometric and electronic structural requirements to activate peroxo reactivity, the active peroxo intermediate in 4-aminobenzoate N-oxygenase (AurF) has been characterized spectroscopically and computationally. A magnetic circular dichroism study of reduced AurF shows that its electronic and geometric structures are poised to react rapidly with O 2. Nuclear resonance vibrational spectroscopic definition of the peroxo intermediate formed in this reactionmore » shows that the active intermediate has a protonated peroxo bridge. Density functional theory computations on the structure established here show that the protonation activates peroxide for electrophilic/single-electron-transfer reactivity. As a result, this activation of peroxide by protonation is likely also relevant to the reactive peroxo intermediates in other binuclear non-heme iron enzymes.« less

Nonadiabatic rate constants for proton transfer and proton-coupled electron transfer reactions in solution: Effects of quadratic term in the vibronic coupling expansion

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

Soudackov, Alexander V.; Hammes-Schiffer, Sharon

2015-11-21

Rate constant expressions for vibronically nonadiabatic proton transfer and proton-coupled electron transfer reactions are presented and analyzed. The regimes covered include electronically adiabatic and nonadiabatic reactions, as well as high-frequency and low-frequency proton donor-acceptor vibrational modes. These rate constants differ from previous rate constants derived with the cumulant expansion approach in that the logarithmic expansion of the vibronic coupling in terms of the proton donor-acceptor distance includes a quadratic as well as a linear term. The analysis illustrates that inclusion of this quadratic term in the framework of the cumulant expansion framework may significantly impact the rate constants at highmore » temperatures for proton transfer interfaces with soft proton donor-acceptor modes that are associated with small force constants and weak hydrogen bonds. The effects of the quadratic term may also become significant in these regimes when using the vibronic coupling expansion in conjunction with a thermal averaging procedure for calculating the rate constant. In this case, however, the expansion of the coupling can be avoided entirely by calculating the couplings explicitly for the range of proton donor-acceptor distances sampled. The effects of the quadratic term for weak hydrogen-bonding systems are less significant for more physically realistic models that prevent the sampling of unphysical short proton donor-acceptor distances. Additionally, the rigorous relation between the cumulant expansion and thermal averaging approaches is clarified. In particular, the cumulant expansion rate constant includes effects from dynamical interference between the proton donor-acceptor and solvent motions and becomes equivalent to the thermally averaged rate constant when these dynamical effects are neglected. This analysis identifies the regimes in which each rate constant expression is valid and thus will be important for future applications to proton transfer and proton-coupled electron transfer in chemical and biological processes.« less

Using gEUD based plan analysis method to evaluate proton vs. photon plans for lung cancer radiation therapy.

PubMed

Xiao, Zhiyan; Zou, Wei J; Chen, Ting; Yue, Ning J; Jabbour, Salma K; Parikh, Rahul; Zhang, Miao

2018-03-01

The goal of this study was to exam the efficacy of current DVH based clinical guidelines draw from photon experience for lung cancer radiation therapy on proton therapy. Comparison proton plans and IMRT plans were generated for 10 lung patients treated in our proton facility. A gEUD based plan evaluation method was developed for plan evaluation. This evaluation method used normal lung gEUD(a) curve in which the model parameter "a" was sampled from the literature reported value. For all patients, the proton plans delivered lower normal lung V 5 Gy with similar V 20 Gy and similar target coverage. Based on current clinical guidelines, proton plans were ranked superior to IMRT plans for all 10 patients. However, the proton and IMRT normal lung gEUD(a) curves crossed for 8 patients within the tested range of "a", which means there was a possibility that proton plan would be worse than IMRT plan for lung sparing. A concept of deficiency index (DI) was introduced to quantify the probability of proton plans doing worse than IMRT plans. By applying threshold on DI, four patients' proton plan was ranked inferior to the IMRT plan. Meanwhile if a threshold to the location of curve crossing was applied, 6 patients' proton plan was ranked inferior to the IMRT plan. The contradictory ranking results between the current clinical guidelines and the gEUD(a) curve analysis demonstrated there is potential pitfalls by applying photon experience directly to the proton world. A comprehensive plan evaluation based on radio-biological models should be carried out to decide if a lung patient would really be benefit from proton therapy. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Computational investigation of drug-resistant mutant of M2 proton channel (S31N) against rimantadine.

PubMed

Karthick, V; Ramanathan, K

2014-11-01

M2 proton channel is the target for treating the patients who ere suffering from influenza A infection, which facilitates the spread of virions. Amantadine and rimantadine are adamantadine-based drugs, which target M2 proton channel and inhibit the viral replication. Preferably, rimantadine drug is used more than amantadine because of its fewer side effects. However, S31N mutation in the M2 proton channel was highly resistant to the rimantadine drug. Therefore, in the present study, we focused to understand the drug-resistance mechanism of S31N mutation with the aid of molecular docking and dynamics approach. The docking analysis undoubtedly indicates that affinity for rimantadine with mutant-type M2 proton channel is significantly lesser than the native-type M2 proton channel. In addition, RMSD, RMSF, and principal component analysis suggested that the mutation shows increased flexibility. Furthermore, the intermolecular hydrogen bonds analysis showed that there is a complete loss of hydrogen bonds in the mutant complex. On the whole, we conclude that the intermolecular contact was maintained by D-44, a key residue for stable binding of rimantadine. These findings are certainly helpful for better understanding of drug-resistance mechanism and also helpful for designing new drugs for treating influenza infection against drug-resistance target.

Umbrella sampling of proton transfer in a creatine-water system

NASA Astrophysics Data System (ADS)

Ivchenko, Olga; Bachert, Peter; Imhof, Petra

2014-04-01

Proton transfer reactions are among the most common processes in chemistry and biology. Proton transfer between creatine and surrounding solvent water is underlying the chemical exchange saturation transfer used as a contrast in magnetic resonance imaging. The free energy barrier, determined by first-principles umbrella sampling simulations (EaDFT 3 kcal/mol) is in the same order of magnitude as the experimentally obtained activation energy. The underlying mechanism is a first proton transfer from the guanidinium group to the water pool, followed by a second transition where a proton is "transferred back" from the nearest water molecule to the deprotonated nitrogen atom of creatine.

Flares, ejections, proton events

NASA Astrophysics Data System (ADS)

Belov, A. V.

2017-11-01

Statistical analysis is performed for the relationship of coronal mass ejections (CMEs) and X-ray flares with the fluxes of solar protons with energies >10 and >100 MeV observed near the Earth. The basis for this analysis was the events that took place in 1976-2015, for which there are reliable observations of X-ray flares on GOES satellites and CME observations with SOHO/LASCO coronagraphs. A fairly good correlation has been revealed between the magnitude of proton enhancements and the power and duration of flares, as well as the initial CME speed. The statistics do not give a clear advantage either to CMEs or the flares concerning their relation with proton events, but the characteristics of the flares and ejections complement each other well and are reasonable to use together in the forecast models. Numerical dependences are obtained that allow estimation of the proton fluxes to the Earth expected from solar observations; possibilities for improving the model are discussed.

Protons are one of the limiting factors in determining sensitivity of nano surface-assisted (+)-mode LDI MS analyses.

PubMed

Cho, Eunji; Ahn, Miri; Kim, Young Hwan; Kim, Jongwon; Kim, Sunghwan

2013-10-01

A proton source employing a nanostructured gold surface for use in (+)-mode laser desorption ionization mass spectrometry (LDI-MS) was evaluated. Analysis of perdeuterated polyaromatic hydrocarbon compound dissolved in regular toluene, perdeuterated toluene, and deuterated methanol all showed that protonated ions were generated irregardless of solvent system. Therefore, it was concluded that residual water on the surface of the LDI plate was the major source of protons. The fact that residual water remaining after vacuum drying was the source of protons suggests that protons may be the limiting reagent in the LDI process and that overall ionization efficiency can be improved by incorporating an additional proton source. When extra proton sources, such as thiolate compounds and/or citric acid, were added to a nanostructured gold surface, the protonated signal abundance increased. These data show that protons are one of the limiting components in (+)-mode LDI MS analyses employing nanostructured gold surfaces. Therefore, it has been suggested that additional efforts are required to identify compounds that can act as proton donors without generating peaks that interfere with mass spectral interpretation.

Contribution of proton leak to oxygen consumption in skeletal muscle during intense exercise is very low despite large contribution at rest

PubMed Central

2017-01-01

A computer model was used to simulate the dependence of protonmotive force (Δp), proton leak and phenomenological (involving proton leak) ATP/O2 ratio on work intensity in skeletal muscle. Δp, NADH and proton leak decreased with work intensity. The contribution of proton leak to oxygen consumption (V˙O2) decreased from about 60% at rest to about 3 and 1% at moderate and heavy/severe exercise, respectively, while the ATP/O2 ratio increased from 2.1 to 5.5 and 5.7. A two-fold increase in proton leak activity or its decrease to zero decreased/increased the ATP/O2 ratio by only about 3 and 1% during moderate and heavy/severe exercise, respectively. The low contribution of proton leak to V˙O2 in intensively working skeletal muscle was mostly caused by a huge increase in ATP usage intensity during rest-to-work transition, while OXPHOS, and thus oxidative ATP supply and V˙O2 related to it, was mostly stimulated by high each-step activation (ESA) of OXPHOS complexes. The contribution of proton leak to V˙O2 and ATP/O2 ratio in isolated mitochondria should not be directly extrapolated to working muscle, as mitochondria lack ESA, at least in the absence of Ca2+, and therefore V˙O2 cannot be elevated as much as in intact muscle. PMID:29045413

Contribution of proton leak to oxygen consumption in skeletal muscle during intense exercise is very low despite large contribution at rest.

PubMed

Korzeniewski, Bernard

2017-01-01

A computer model was used to simulate the dependence of protonmotive force (Δp), proton leak and phenomenological (involving proton leak) ATP/O2 ratio on work intensity in skeletal muscle. Δp, NADH and proton leak decreased with work intensity. The contribution of proton leak to oxygen consumption ([Formula: see text]) decreased from about 60% at rest to about 3 and 1% at moderate and heavy/severe exercise, respectively, while the ATP/O2 ratio increased from 2.1 to 5.5 and 5.7. A two-fold increase in proton leak activity or its decrease to zero decreased/increased the ATP/O2 ratio by only about 3 and 1% during moderate and heavy/severe exercise, respectively. The low contribution of proton leak to [Formula: see text] in intensively working skeletal muscle was mostly caused by a huge increase in ATP usage intensity during rest-to-work transition, while OXPHOS, and thus oxidative ATP supply and [Formula: see text] related to it, was mostly stimulated by high each-step activation (ESA) of OXPHOS complexes. The contribution of proton leak to [Formula: see text] and ATP/O2 ratio in isolated mitochondria should not be directly extrapolated to working muscle, as mitochondria lack ESA, at least in the absence of Ca2+, and therefore [Formula: see text] cannot be elevated as much as in intact muscle.

Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons

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

Lin, Jiusheng; Pozharski, Edwin; Wilson, Mark A.

Short hydrogen bonds (H-bonds) have been proposed to play key functional roles in several proteins. The location of the proton in short H-bonds is of central importance, as proton delocalization is a defining feature of low-barrier hydrogen bonds (LBHBs). Experimentally determining proton location in H-bonds is challenging. Here, bond length analysis of atomic (1.15–0.98 Å) resolution X-ray crystal structures of the human protein DJ-1 and its bacterial homologue, YajL, was used to determine the protonation states of H-bonded carboxylic acids. DJ-1 contains a buried, dimer-spanning 2.49 Å H-bond between Glu15 and Asp24 that satisfies standard donor–acceptor distance criteria for amore » LBHB. Bond length analysis indicates that the proton is localized on Asp24, excluding a LBHB at this location. However, similar analysis of the Escherichia coli homologue YajL shows both residues may be protonated at the H-bonded oxygen atoms, potentially consistent with a LBHB. A Protein Data Bank-wide screen identifies candidate carboxylic acid H-bonds in approximately 14% of proteins, which are typically short [O–O> = 2.542(2) Å]. Chemically similar H-bonds between hydroxylated residues (Ser/Thr/Tyr) and carboxylates show a trend of lengthening O–O distance with increasing H-bond donor pK a. This trend suggests that conventional electronic effects provide an adequate explanation for short, charge-assisted carboxylic acid–carboxylate H-bonds in proteins, without the need to invoke LBHBs in general. This study demonstrates that bond length analysis of atomic resolution X-ray crystal structures provides a useful experimental test of certain candidate LBHBs.« less

Short Carboxylic Acid-Carboxylate Hydrogen Bonds Can Have Fully Localized Protons.

PubMed

Lin, Jiusheng; Pozharski, Edwin; Wilson, Mark A

2017-01-17

Short hydrogen bonds (H-bonds) have been proposed to play key functional roles in several proteins. The location of the proton in short H-bonds is of central importance, as proton delocalization is a defining feature of low-barrier hydrogen bonds (LBHBs). Experimentally determining proton location in H-bonds is challenging. Here, bond length analysis of atomic (1.15-0.98 Å) resolution X-ray crystal structures of the human protein DJ-1 and its bacterial homologue, YajL, was used to determine the protonation states of H-bonded carboxylic acids. DJ-1 contains a buried, dimer-spanning 2.49 Å H-bond between Glu15 and Asp24 that satisfies standard donor-acceptor distance criteria for a LBHB. Bond length analysis indicates that the proton is localized on Asp24, excluding a LBHB at this location. However, similar analysis of the Escherichia coli homologue YajL shows both residues may be protonated at the H-bonded oxygen atoms, potentially consistent with a LBHB. A Protein Data Bank-wide screen identifies candidate carboxylic acid H-bonds in approximately 14% of proteins, which are typically short [⟨d O-O ⟩ = 2.542(2) Å]. Chemically similar H-bonds between hydroxylated residues (Ser/Thr/Tyr) and carboxylates show a trend of lengthening O-O distance with increasing H-bond donor pK a . This trend suggests that conventional electronic effects provide an adequate explanation for short, charge-assisted carboxylic acid-carboxylate H-bonds in proteins, without the need to invoke LBHBs in general. This study demonstrates that bond length analysis of atomic resolution X-ray crystal structures provides a useful experimental test of certain candidate LBHBs.

Vicinal fluorine-fluorine coupling constants: Fourier analysis.

PubMed

San Fabián, J; Westra Hoekzema, A J A

2004-10-01

Stereochemical dependences of vicinal fluorine-fluorine nuclear magnetic resonance coupling constants (3JFF) have been studied with the multiconfigurational self-consistent field in the restricted active space approach, with the second-order polarization propagator approximation (SOPPA), and with density functional theory. The SOPPA results show the best overall agreement with experimental couplings. The relationship with the dihedral angle between the coupled fluorines has been studied by Fourier analysis, the result is very different from that of proton-proton couplings. The Fourier coefficients do not resemble those of a typical Karplus equation. The four nonrelativistic contributions to the coupling constants of 1,2-difluoroethane configurations have been studied separately showing that up to six Fourier coefficients are required to reproduce the calculated values satisfactorily. Comparison with Fourier coefficients for matching hydrogen fluoride dimer configurations suggests that the higher order Fourier coefficients (Cn> or =3) originate mainly from through-space Fermi contact interaction. The through-space interaction is the main reason 3JFF do not follow the Karplus equation. (c) 2004 American Institute of Physics

Vicinal fluorine-fluorine coupling constants: Fourier analysis

NASA Astrophysics Data System (ADS)

San Fabián, J.; Westra Hoekzema, A. J. A.

2004-10-01

Stereochemical dependences of vicinal fluorine-fluorine nuclear magnetic resonance coupling constants (3JFF) have been studied with the multiconfigurational self-consistent field in the restricted active space approach, with the second-order polarization propagator approximation (SOPPA), and with density functional theory. The SOPPA results show the best overall agreement with experimental couplings. The relationship with the dihedral angle between the coupled fluorines has been studied by Fourier analysis, the result is very different from that of proton-proton couplings. The Fourier coefficients do not resemble those of a typical Karplus equation. The four nonrelativistic contributions to the coupling constants of 1,2-difluoroethane configurations have been studied separately showing that up to six Fourier coefficients are required to reproduce the calculated values satisfactorily. Comparison with Fourier coefficients for matching hydrogen fluoride dimer configurations suggests that the higher order Fourier coefficients (Cn⩾3) originate mainly from through-space Fermi contact interaction. The through-space interaction is the main reason 3JFF do not follow the Karplus equation.

Oxygen Reduction Reaction on Platinum-Terminated “Onion-structured” Alloy Catalysts

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

Herron, Jeffrey A.; Jiao, Jiao; Hahn, Konstanze

Using periodic, self-consistent density functional theory (GGA-PW91) calculations, a series of onion-structured metal alloys have been investigated for their catalytic performance towards the oxygen reduction reaction (ORR). The onion-structures consist of a varying number of atomic layers of one or two metals each, pseudomorphically deposited on top of one another to form the overall structure. All catalysts studied feature a Pt overlayer, and often consist of at least one Pd layer below the surface. Three distinct ORR mechanisms were analyzed on the close-packed facets of all the structures considered. These mechanisms include a direct route of O2 dissociation and twomore » hydrogen-assisted routes of O–O bond-breaking in peroxyl (OOH) and in hydrogen peroxide (HOOH) intermediates. A thermochemical analysis of the elementary steps provides information on the operating potential, and thereby energy efficiency of each electrocatalyst. A Sabatier analysis of catalytic activity based on thermochemistry of proton/electron transfer steps and activation energy barrier for O–O bond-breaking steps leads to a “volcano” relation between the surfaces’ activity and the binding energy of O. Several of the onion-structured alloys studied here show promise for achieving energy efficiency higher than that of Pt, by being active at potentials higher than the operating potential of Pt. Furthermore, some have at least as good activity as pure Pt at that operating potential. Thus, a number of the onion-structured alloys studied here are promising as cathode electrocatalysts in proton exchange membrane fuel cells.« less

Unraveling the mechanism of proton translocation in the extracellular half-channel of bacteriorhodopsin.

PubMed

Ge, Xiaoxia; Gunner, M R

2016-05-01

Bacteriorhodopsin, a light activated protein that creates a proton gradient in halobacteria, has long served as a simple model of proton pumps. Within bacteriorhodopsin, several key sites undergo protonation changes during the photocycle, moving protons from the higher pH cytoplasm to the lower pH extracellular side. The mechanism underlying the long-range proton translocation between the central (the retinal Schiff base SB216, D85, and D212) and exit clusters (E194 and E204) remains elusive. To obtain a dynamic view of the key factors controlling proton translocation, a systematic study using molecular dynamics simulation was performed for eight bacteriorhodopsin models varying in retinal isomer and protonation states of the SB216, D85, D212, and E204. The side-chain orientation of R82 is determined primarily by the protonation states of the residues in the EC. The side-chain reorientation of R82 modulates the hydrogen-bond network and consequently possible pathways of proton transfer. Quantum mechanical intrinsic reaction coordinate calculations of proton-transfer in the methyl guanidinium-hydronium-hydroxide model system show that proton transfer via a guanidinium group requires an initial geometry permitting proton donation and acceptance by the same amine. In all the bacteriorhodopsin models, R82 can form proton wires with both the CC and the EC connected by the same amine. Alternatively, rare proton wires for proton transfer from the CC to the EC without involving R82 were found in an O' state where the proton on D85 is transferred to D212. © 2016 Wiley Periodicals, Inc.

Voltage-gated proton (H(v)1) channels, a singular voltage sensing domain.

PubMed

Castillo, Karen; Pupo, Amaury; Baez-Nieto, David; Contreras, Gustavo F; Morera, Francisco J; Neely, Alan; Latorre, Ramon; Gonzalez, Carlos

2015-11-14

The main role of voltage-gated proton channels (Hv1) is to extrude protons from the intracellular milieu when, mediated by different cellular processes, the H(+) concentration increases. Hv1 are exquisitely selective for protons and their structure is homologous to the voltage sensing domain (VSD) of other voltage-gated ion channels like sodium, potassium, and calcium channels. In clear contrast to the classical voltage-dependent channels, Hv1 lacks a pore domain and thus permeation necessarily occurs through the voltage sensing domain. Hv1 channels are activated by depolarizing voltages, and increases in internal proton concentration. It has been proposed that local conformational changes of the transmembrane segment S4, driven by depolarization, trigger the molecular rearrangements that open Hv1. However, it is still unclear how the electromechanical coupling is achieved between the VSD and the potential pore, allowing the proton flux from the intracellular to the extracellular side. Here we provide a revised view of voltage activation in Hv1 channels, offering a comparative scenario with other voltage sensing channels domains. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Coupling Protein Dynamics with Proton Transport in Human Carbonic Anhydrase II

PubMed Central

2016-01-01

The role of protein dynamics in enzyme catalysis is one of the most highly debated topics in enzymology. The main controversy centers around what may be defined as functionally significant conformational fluctuations and how, if at all, these fluctuations couple to enzyme catalyzed events. To shed light on this debate, the conformational dynamics along the transition path surmounting the highest free energy barrier have been herein investigated for the rate limiting proton transport event in human carbonic anhydrase (HCA) II. Special attention has been placed on whether the motion of an excess proton is correlated with fluctuations in the surrounding protein and solvent matrix, which may be rare on the picosecond and subpicosecond time scales of molecular motions. It is found that several active site residues, which do not directly participate in the proton transport event, have a significant impact on the dynamics of the excess proton. These secondary participants are shown to strongly influence the active site environment, resulting in the creation of water clusters that are conducive to fast, moderately slow, or slow proton transport events. The identification and characterization of these secondary participants illuminates the role of protein dynamics in the catalytic efficiency of HCA II. PMID:27063577

Modelling of the batch biosorption system: study on exchange of protons with cell wall-bound mineral ions.

PubMed

Mishra, Vishal

2015-01-01

The interchange of the protons with the cell wall-bound calcium and magnesium ions at the interface of solution/bacterial cell surface in the biosorption system at various concentrations of protons has been studied in the present work. A mathematical model for establishing the correlation between concentration of protons and active sites was developed and optimized. The sporadic limited residence time reactor was used to titrate the calcium and magnesium ions at the individual data point. The accuracy of the proposed mathematical model was estimated using error functions such as nonlinear regression, adjusted nonlinear regression coefficient, the chi-square test, P-test and F-test. The values of the chi-square test (0.042-0.017), P-test (<0.001-0.04), sum of square errors (0.061-0.016), root mean square error (0.01-0.04) and F-test (2.22-19.92) reported in the present research indicated the suitability of the model over a wide range of proton concentrations. The zeta potential of the bacterium surface at various concentrations of protons was observed to validate the denaturation of active sites.

Production and Extraction of [10C]-CO2 From Proton Bombardment of Molten 10B2O3

NASA Astrophysics Data System (ADS)

Schueller, M. J.; Nickles, R. J.; Roberts, A. D.; Jensen, M.

2003-08-01

This work describes the production of 10C (t1/2 = 19 s) from an enriched 10B2O3 target using a CTI RDS-112 11 MeV proton cyclotron. Proton beam heating is used to raise the target to a molten state (˜ 1300 °C), enabling the activity to diffuse to the surface of the melt. An infrared thermocouple monitors the melt temperature. Helium sweep gas then transports the activity to flow-through chemistry processing for human inhalation of 10CO2 for blood flow imaging with Positron Emission Tomography. The temperature-related diffusion of activity out of the white-hot molten glass target is discussed.

Subunit III-depleted cytochrome c oxidase provides insight into the process of proton uptake by proteins

PubMed Central

Varanasi, Lakshman; Hosler, Jonathan P.

2011-01-01

We review studies of subunit III-depleted cytochrome c oxidase (CcO III (−)) that elucidate the structural basis of steady-state proton uptake from solvent into an internal proton transfer pathway. The removal of subunit III from R. sphaeroides CcO makes proton uptake into the D pathway a rate-determining step, such that measurements of the pH dependence of steady-state O2 consumption can be used to compare the rate and functional pKa of proton uptake by D pathways containing different initial proton acceptors. The removal of subunit III also promotes spontaneous suicide inactivation by CcO, greatly shortening its catalytic lifespan. Because the probability of suicide inactivation is controlled by the rate at which the D pathway delivers protons to the active site, measurements of catalytic lifespan provide a second method to compare the relative efficacy of proton uptake by engineered CcO III (−) forms. These simple experimental systems have been used to explore general questions of proton uptake by proteins, such as the functional value of an initial proton acceptor, whether an initial acceptor must be surface-exposed, which side chains will function as initial proton acceptors and whether multiple acceptors can speed proton uptake. PMID:22023935

Role of Hydrogen Bonding in Photoinduced Electron-Proton Transfer from Phenols to a Polypyridine Ru Complex with a Proton-Accepting Ligand

DOE PAGES

Lymar, Sergei V.; Ertem, Mehmed Z.; Lewandowska-Andralojc, Anna; ...

2017-08-09

Electron-proton transfer, EPT, from phenols to a triplet MLCT-excited Ru polypyridine complex containing an uncoordinated nitrogen site, 1(T), can be described by a kinetic model that accounts for the H-bonding of 1(T) to phenol, 1(T) to solvent, and phenol to solvent. The latter plays a major role in the kinetic solvent effect and commonly precludes simultaneous determination of the EPT rate constant and 1(T)-phenol H-bonding constant. A number of these quantities previously reported for similar systems are shown to be in error due to an inconsistent data analysis. In conclusion, control experiments replacing either 1(T) by its structural isomer withmore » a sterically screened nitrogen site or phenol by its H-bonding surrogate, trifluoroethanol, and the observation of negative activation enthalpies for the overall reactions between 1(T) and phenols lend support to the proposed model and provide evidence for the formation of a precursor H-bonded complex between the reactants, which is a prerequisite for EPT.« less

Role of Hydrogen Bonding in Photoinduced Electron-Proton Transfer from Phenols to a Polypyridine Ru Complex with a Proton-Accepting Ligand

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

Lymar, Sergei V.; Ertem, Mehmed Z.; Lewandowska-Andralojc, Anna

Electron-proton transfer, EPT, from phenols to a triplet MLCT-excited Ru polypyridine complex containing an uncoordinated nitrogen site, 1(T), can be described by a kinetic model that accounts for the H-bonding of 1(T) to phenol, 1(T) to solvent, and phenol to solvent. The latter plays a major role in the kinetic solvent effect and commonly precludes simultaneous determination of the EPT rate constant and 1(T)-phenol H-bonding constant. A number of these quantities previously reported for similar systems are shown to be in error due to an inconsistent data analysis. In conclusion, control experiments replacing either 1(T) by its structural isomer withmore » a sterically screened nitrogen site or phenol by its H-bonding surrogate, trifluoroethanol, and the observation of negative activation enthalpies for the overall reactions between 1(T) and phenols lend support to the proposed model and provide evidence for the formation of a precursor H-bonded complex between the reactants, which is a prerequisite for EPT.« less

A self-assembled 2D/2D-type protonated carbon nitride-modified graphene oxide nanocomposite with improved photocatalytic activity

NASA Astrophysics Data System (ADS)

Xie, Linfang; Ni, Jie; Tang, Bo; He, Guangyu; Chen, Haiqun

2018-03-01

A surface charge modified g-C3N4 was successfully prepared by protonation of nitric acid. Combination of the protonated g-C3N4 (pCN) and graphene oxide (GO) layers created a 2D/2D-type composite (pCN/GO) under the synergistic effect of sonication-exfoliation and self-assembly. The obtained 2D nanostructure of pCN/GO was explored by electron microscopy analysis. The photocatalytic degradation of rhodamine B (RhB) and ciprofloxacin (CIP) showed a distinctly high efficiency of pCN/GO-5% with excellent stability, which is superior not only to that of g-C3N4, pCN and g-C3N4/GO-5% nanocomposites we prepared, but also to what was reported previously. The optimized combination of GO and pCN afforded the pCN/GO composite intimate interfacial contact within the heterojunction, which promoted the separation of photogenerated electron-hole pairs as evidenced by zeta potential, photoluminescence and photocurrent measurements. A visible-light photocatalytic degradation mechanism associated with pCN/GO nanocomposites was also proposed.

Hexameric and pentameric complexes of the ExbBD energizer in the Ton system.

PubMed

Maki-Yonekura, Saori; Matsuoka, Rei; Yamashita, Yoshiki; Shimizu, Hirofumi; Tanaka, Maiko; Iwabuki, Fumie; Yonekura, Koji

2018-04-17

Gram-negative bacteria import essential nutrients such as iron and vitamin B 12 through outer membrane receptors. This process utilizes proton motive force harvested by the Ton system made up of three inner membrane proteins, ExbB, ExbD and TonB. ExbB and ExbD form the proton channel that energizes uptake through TonB. Recently, crystal structures suggest that the ExbB pentamer is the scaffold. Here, we present structures of hexameric complexes of ExbB and ExbD revealed by X-ray crystallography and single particle cryo-EM. Image analysis shows that hexameric and pentameric complexes coexist, with the proportion of hexamer increasing with pH. Channel current measurement and 2D crystallography support the existence and transition of the two oligomeric states in membranes. The hexameric complex consists of six ExbB subunits and three ExbD transmembrane helices enclosed within the central channel. We propose models for activation/inactivation associated with hexamer and pentamer formation and utilization of proton motive force. © 2018, Maki-Yonekura et al.

Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB

PubMed Central

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

2014-01-01

Membrane transporters of the RND superfamily confer multidrug resistance to pathogenic bacteria, and are essential for cholesterol metabolism and embryonic development in humans. We use high-resolution X-ray crystallography and computational methods to delineate the mechanism of the homotrimeric RND-type proton/drug antiporter AcrB, the active component of the major efflux system AcrAB-TolC in Escherichia coli, and one most complex and intriguing membrane transporters known to date. Analysis of wildtype AcrB and four functionally-inactive variants reveals an unprecedented mechanism that involves two remote alternating-access conformational cycles within each protomer, namely one for protons in the transmembrane region and another for drugs in the periplasmic domain, 50 Å apart. Each of these cycles entails two distinct types of collective motions of two structural repeats, coupled by flanking α-helices that project from the membrane. Moreover, we rationalize how the cross-talk among protomers across the trimerization interface might lead to a more kinetically efficient efflux system. DOI: http://dx.doi.org/10.7554/eLife.03145.001 PMID:25248080

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

Energy dependence of SEP electron and proton onset times

NASA Astrophysics Data System (ADS)

Xie, H.; Mäkelä, P.; Gopalswamy, N.; St. Cyr, O. C.

2016-07-01

We study the large solar energetic particle (SEP) events that were detected by GOES in the >10 MeV energy channel during December 2006 to March 2014. We derive and compare solar particle release (SPR) times for the 0.25-10.4 MeV electrons and 10-100 MeV protons for the 28 SEP events. In the study, the electron SPR times are derived with the time-shifting analysis (TSA) and the proton SPR times are derived using both the TSA and the velocity dispersion analysis (VDA). Electron anisotropies are computed to evaluate the amount of scattering for the events under study. Our main results include (1) near-relativistic electrons and high-energy protons are released at the same time within 8 min for most (16 of 23) SEP events. (2)There exists a good correlation between electron and proton acceleration, peak intensity, and intensity time profiles. (3) The TSA SPR times for 90.5 MeV and 57.4 MeV protons have maximum errors of 6 min and 10 min compared to the proton VDA release times, respectively, while the maximum error for 15.4 MeV protons can reach to 32 min. (4) For 7 low-intensity events of the 23, large delays occurred for 6.5 MeV electrons and 90.5 MeV protons relative to 0.5 MeV electrons. Whether these delays are due to times needed for the evolving shock to be strengthened or due to particle transport effects remains unsolved.

Recent advances in X-ray microanalysis in dermatology

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

Forslind, B.; Grundin, T.G.; Lindberg, M.

1985-01-01

Electron microprobe and proton microprobe X-ray analysis can be used in several areas of dermatological research. With a proton probe, the distribution of trace elements in human hair can be determined. Electron microprobe analysis on freeze-dried cryosections of guinea-pig and human epidermis shows a marked gradient of Na, P and K over the stratum granulosum. In sections of freeze-substituted human skin this gradient is less steep. This difference is likely to be due to a decrease in water content of the epidermis towards the stratum corneum. Electron microprobe analysis of the epidermis can, for analysis of trace elements, be complementedmore » by the proton microprobe. Quantitative agreement between the two techniques can be obtained by the use of a standard. Proton microprobe analysis was used to determine the distribution of Ni or Cr in human epidermis exposed to nickel or chromate ions. Possible differences in water content between the stratum corneum of patients with atopic eczema and normal stratum corneum was investigated in skin freeze-substituted with Br-doped resin. No significant differences were observed.« less

Charge stabilization and entropy reduction of central lysine residues in fructose-bisphosphate aldolase.

PubMed

St-Jean, Miguel; Blonski, Casimir; Sygusch, Jurgen

2009-06-02

Fructose-1,6-bisphosphate muscle aldolase is an essential glycolytic enzyme that catalyzes reversible carbon-carbon bond formation by cleaving fructose 1,6-bisphosphate to yield dihydroxyacetone phosphate (DHAP) and d-glyceraldehyde phosphate. To elucidate the mechanistic role of conserved amino acid Asp-33, Asn-33 and Ser-33 mutants were examined by kinetic and structural analyses. The mutations significantly compromised enzymatic activity and carbanion oxidation in presence of DHAP. Detailed structural analysis demonstrated that, like native crystals, Asp-33 mutant crystals, soaked in DHAP solutions, trapped Schiff base-derived intermediates covalently attached to Lys-229. The mutant structures, however, exhibited an abridged conformational change with the helical region (34-65) flanking the active site as well as pK(a) reductions and increased side chain disorder by central lysine residues, Lys-107 and Lys-146. These changes directly affect their interaction with the C-terminal Tyr-363, consistent with the absence of active site binding by the C-terminal region in the presence of phosphate. Lys-146 pK(a) reduction and side chain disorder would further compromise charge stabilization during C-C bond cleavage and proton transfer during enamine formation. These mechanistic impediments explain diminished catalytic activity and a reduced level of carbanion oxidation and are consistent with rate-determining proton transfer observed in the Asn-33 mutant. Asp-33 reduces the entropic cost and augments the enthalpic gain during catalysis by rigidifying Lys-107 and Lys-146, stabilizing their protonated forms, and promoting a conformational change triggered by substrate or obligate product binding, which lower kinetic barriers in C-C bond cleavage and Schiff base-enamine interconversion.

Advances in compact proton spectrometers for inertial-confinement fusion and plasma nuclear science.

PubMed

Seguin, F H; Sinenian, N; Rosenberg, M; Zylstra, A; Manuel, M J-E; Sio, H; Waugh, C; Rinderknecht, H G; Johnson, M Gatu; Frenje, J; Li, C K; Petrasso, R; Sangster, T C; Roberts, S

2012-10-01

Compact wedge-range-filter proton spectrometers cover proton energies ∼3-20 MeV. They have been used at the OMEGA laser facility for more than a decade for measuring spectra of primary D(3)He protons in D(3)He implosions, secondary D(3)He protons in DD implosions, and ablator protons in DT implosions; they are now being used also at the National Ignition Facility. The spectra are used to determine proton yields, shell areal density at shock-bang time and compression-bang time, fuel areal density, and implosion symmetry. There have been changes in fabrication and in analysis algorithms, resulting in a wider energy range, better accuracy and precision, and better robustness for survivability with indirect-drive inertial-confinement-fusion experiments.

Thermal annealing response following irradiation of a CMOS imager for the JUICE JANUS instrument

NASA Astrophysics Data System (ADS)

Lofthouse-Smith, D.-D.; Soman, M. R.; Allanwood, E. A. H.; Stefanov, K. D.; Holland, A. D.; Leese, M.; Turne, P.

2018-03-01

ESA's JUICE (JUpiter ICy moon Explorer) spacecraft is an L-class mission destined for the Jovian system in 2030. Its primary goals are to investigate the conditions for planetary formation and the emergence of life, and how does the solar system work. The JANUS camera, an instrument on JUICE, uses a 4T back illuminated CMOS image sensor, the CIS115 designed by Teledyne e2v. JANUS imager test campaigns are studying the CIS115 following exposure to gammas, protons, electrons and heavy ions, simulating the harsh radiation environment present in the Jovian system. The degradation of 4T CMOS device performance following proton fluences is being studied, as well as the effectiveness of thermal annealing to reverse radiation damage. One key parameter for the JANUS mission is the Dark current of the CIS115, which has been shown to degrade in previous radiation campaigns. A thermal anneal of the CIS115 has been used to accelerate any annealing following the irradiation as well as to study the evolution of any performance characteristics. CIS115s have been irradiated to double the expected End of Life (EOL) levels for displacement damage radiation (2×1010 protons, 10 MeV equivalent). Following this, devices have undergone a thermal anneal cycle at 100oC for 168 hours to reveal the extent to which CIS115 recovers pre-irradiation performance. Dark current activation energy analysis following proton fluence gives information on trap species present in the device and how effective anneal is at removing these trap species. Thermal anneal shows no quantifiable change in the activation energy of the dark current following irradiation.

Driving force analysis of proton tunnelling across a reactivity series for an enzyme-substrate complex.

PubMed

Hothi, Parvinder; Hay, Sam; Roujeinikova, Anna; Sutcliffe, Michael J; Lee, Michael; Leys, David; Cullis, Paul M; Scrutton, Nigel S

2008-11-24

Quantitative structure-activity relationships are widely used to probe C-H bond breakage by quinoprotein enzymes. However, we showed recently that p-substituted benzylamines are poor reactivity probes for the quinoprotein aromatic amine dehydrogenase (AADH) because of a requirement for structural change in the enzyme-substrate complex prior to C-H bond breakage. This rearrangement is partially rate limiting, which leads to deflated kinetic isotope effects for p-substituted benzylamines. Here we report reactivity (driving force) studies of AADH with p-substituted phenylethylamines for which the kinetic isotope effect (approximately 16) accompanying C-H/C-(2)H bond breakage is elevated above the semi-classical limit. We show bond breakage occurs by quantum tunnelling and that within the context of the environmentally coupled framework for H-tunnelling the presence of the p-substituent places greater demand on the apparent need for fast promoting motions. The crystal structure of AADH soaked with phenylethylamine or methoxyphenylethylamine indicates that the structural change identified with p-substituted benzylamines should not limit the reaction with p-substituted phenylethylamines. This is consistent with the elevated kinetic isotope effects measured with p-substituted phenylethylamines. We find a good correlation in the rate constant for proton transfer with bond dissociation energy for the reactive C-H bond, consistent with a rate that is limited by a Marcus-like tunnelling mechanism. As the driving force becomes larger, the rate of proton transfer increases while the Marcus activation energy becomes smaller. This is the first experimental report of the driving force perturbation of H-tunnelling in enzymes using a series of related substrates. Our study provides further support for proton tunnelling in AADH.

Transforming in-situ observations of CME-driven shock accelerated protons into the shock's reference frame.

NASA Astrophysics Data System (ADS)

Robinson, I. M.; Simnett, G. M.

2005-07-01

We examine the solar energetic particle event following solar activity from 14, 15 April 2001 which includes a "bump-on-the-tail" in the proton energy spectra at 0.99 AU from the Sun. We find this population was generated by a CME-driven shock which arrived at 0.99 AU around midnight 18 April. As such this population represents an excellent opportunity to study in isolation, the effects of proton acceleration by the shock. The peak energy of the bump-on-the-tail evolves to progressively lower energies as the shock approaches the observing spacecraft at the inner Lagrange point. Focusing on the evolution of this peak energy we demonstrate a technique which transforms these in-situ spectral observations into a frame of reference co-moving with the shock whilst making allowance for the effects of pitch angle scattering and focusing. The results of this transform suggest the bump-on-the-tail population was not driven by the 15 April activity but was generated or at least modulated by a CME-driven shock which left the Sun on 14 April. The existence of a bump-on-the-tail population is predicted by models in Rice et al. (2003) and Li et al. (2003) which we compare with observations and the results of our analysis in the context of both the 14 April and 15 April CMEs. We find an origin of the bump-on-the-tail at the 14 April CME-driven shock provides better agreement with these modelled predictions although some discrepancy exists as to the shock's ability to accelerate 100 MeV protons. Keywords. Solar physics, astrophysics and astronomy (Energetic particles; Flares and mass ejections) Space plasma physics (Transport processes)

Analysis by metadynamics simulation of binding pathway of influenza virus M2 channel blockers.

PubMed

Sakai, Yuri; Kawaguchi, Atsushi; Nagata, Kyosuke; Hirokawa, Takatsugu

2018-01-01

M2 protein of influenza A virus is a proton channel spanning the viral envelope. Activity of this proton channel is required for uncoating of viral particles and equilibrating the pH across the trans Golgi apparatus, which prevents conformational change in hemagglutinin. Amantadine, an anti-influenza A virus drug, inhibits M2 proton channel activity by binding to the channel pore; however, most currently circulating influenza A viruses are amantadine-resistant. The most prevalent resistant mutation is a substitution from Ser31 to Asn31 in M2. Further atomistic analysis of ligand-M2 complexes is needed to provide new approaches for the design of novel M2 channel blockers. Here, the free energy profiles of the binding kinetics of M2 channel blockers were examined by well-tempered metadynamics simulations and it was found that amantadine first binds to Asp24 of S31 M2 and forms a metastable conformation. In contrast, the free energy profiles of adamantyl bromothiophene dual inhibitor with either S31 M2 or N31 M2 are broad funnel-shaped curves, suggesting that adamantyl bromothiophene does not form metastable complexes with M2. The trajectory of well-tempered metadynamics simulations revealed that steric hindrance between adamantyl bromothiophene and S31 M2 interrupts formation of a metastable conformation at Asp24 and that a halogen bond between the bromine atom and N31 is responsible for pulling down the ligand to the channel pore of N31 M2 in the absence of a metastable state. Binding pathways of M2 channel blockers to M2 are here proposed on the basis of these findings; they may provide new approaches to designing further M2 channel blockers. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

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.

Long-range electrostatics-induced two-proton transfer captured by neutron crystallography in an enzyme catalytic site

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

Gerlits, Oksana; Wymore, Troy; Das, Amit

Neutron crystallography was used to directly locate two protons before and after a pH-induced two-proton transfer between catalytic aspartic acid residues and the hydroxy group of the bound clinical drug darunavir, located in the catalytic site of enzyme HIV-1 protease. The two-proton transfer is triggered by electrostatic effects arising from protonation state changes of surface residues far from the active site. The mechanism and pH effect are supported by quantum mechanics/molecular mechanics (QM/MM) calculations. The low-pH proton configuration in the catalytic site is deemed critical for the catalytic action of this enzyme and may apply more generally to other asparticmore » proteases. Neutrons therefore represent a superb probe to obtain structural details for proton transfer reactions in biological systems at a truly atomic level.« less

Long-range electrostatics-induced two-proton transfer captured by neutron crystallography in an enzyme catalytic site

DOE PAGES

Gerlits, Oksana; Wymore, Troy; Das, Amit; ...

2016-03-09

Neutron crystallography was used to directly locate two protons before and after a pH-induced two-proton transfer between catalytic aspartic acid residues and the hydroxy group of the bound clinical drug darunavir, located in the catalytic site of enzyme HIV-1 protease. The two-proton transfer is triggered by electrostatic effects arising from protonation state changes of surface residues far from the active site. The mechanism and pH effect are supported by quantum mechanics/molecular mechanics (QM/MM) calculations. The low-pH proton configuration in the catalytic site is deemed critical for the catalytic action of this enzyme and may apply more generally to other asparticmore » proteases. Neutrons therefore represent a superb probe to obtain structural details for proton transfer reactions in biological systems at a truly atomic level.« less

Long-Range Electrostatics-Induced Two-Proton Transfer Captured by Neutron Crystallography in an Enzyme Catalytic Site.

PubMed

Gerlits, Oksana; Wymore, Troy; Das, Amit; Shen, Chen-Hsiang; Parks, Jerry M; Smith, Jeremy C; Weiss, Kevin L; Keen, David A; Blakeley, Matthew P; Louis, John M; Langan, Paul; Weber, Irene T; Kovalevsky, Andrey

2016-04-11

Neutron crystallography was used to directly locate two protons before and after a pH-induced two-proton transfer between catalytic aspartic acid residues and the hydroxy group of the bound clinical drug darunavir, located in the catalytic site of enzyme HIV-1 protease. The two-proton transfer is triggered by electrostatic effects arising from protonation state changes of surface residues far from the active site. The mechanism and pH effect are supported by quantum mechanics/molecular mechanics (QM/MM) calculations. The low-pH proton configuration in the catalytic site is deemed critical for the catalytic action of this enzyme and may apply more generally to other aspartic proteases. Neutrons therefore represent a superb probe to obtain structural details for proton transfer reactions in biological systems at a truly atomic level. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

THE MULTIELEMENTAL ANALYSIS OF DRINKING WATER USING PROTON-INDUCED X-RAY EMISSION (PIXE)

EPA Science Inventory

A new, rapid, and economical method for the multielemental analysis of drinking water samples is described. The concentrations of 76 elements heavier than aluminum are determined using proton-induced x-ray emission (PIXE) technology. The concentration of sodium is evaluated using...

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 transfer reactions and dynamics in CH(3)OH-H(3)O(+)-H(2)O complexes.

PubMed

Sagarik, Kritsana; Chaiwongwattana, Sermsiri; Vchirawongkwin, Viwat; Prueksaaroon, Supakit

2010-01-28

Proton transfer reactions and dynamics in hydrated complexes formed from CH(3)OH, H(3)O(+) and H(2)O were studied using theoretical methods. The investigations began with searching for equilibrium structures at low hydration levels using the DFT method, from which active H-bonds in the gas phase and continuum aqueous solution were characterized and analyzed. Based on the asymmetric stretching coordinates (Deltad(DA)), four H-bond complexes were identified as potential transition states, in which the most active unit is represented by an excess proton nearly equally shared between CH(3)OH and H(2)O. These cannot be definitive due to the lack of asymmetric O-H stretching frequencies (nu(OH)) which are spectral signatures of transferring protons. Born-Oppenheimer molecular dynamics (BOMD) simulations revealed that, when the thermal energy fluctuations and dynamics were included in the model calculations, the spectral signatures at nu(OH) approximately 1000 cm(-1) appeared. In continuum aqueous solution, the H-bond complex with incomplete water coordination at charged species turned out to be the only active transition state. Based on the assumption that the thermal energy fluctuations and dynamics could temporarily break the H-bonds linking the transition state complex and water molecules in the second hydration shell, elementary reactions of proton transfer were proposed. The present study showed that, due to the coupling among various vibrational modes, the discussions on proton transfer reactions cannot be made based solely on static proton transfer potentials. Inclusion of thermal energy fluctuations and dynamics in the model calculations, as in the case of BOMD simulations, together with systematic IR spectral analyses, have been proved to be the most appropriate theoretical approaches.

Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses

PubMed Central

Tobo, Ayaka; Tobo, Masayuki; Nakakura, Takashi; Ebara, Masashi; Tomura, Hideaki; Mogi, Chihiro; Im, Dong-Soon; Murata, Naoya; Kuwabara, Atsushi; Ito, Saki; Fukuda, Hayato; Arisawa, Mitsuhiro; Shuto, Satoshi; Nakaya, Michio; Kurose, Hitoshi; Sato, Koichi; Okajima, Fumikazu

2015-01-01

G protein-coupled receptor 4 (GPR4), previously proposed as the receptor for sphingosylphosphorylcholine, has recently been identified as the proton-sensing G protein-coupled receptor (GPCR) coupling to multiple intracellular signaling pathways, including the Gs protein/cAMP and G13 protein/Rho. In the present study, we characterized some imidazopyridine compounds as GPR4 modulators that modify GPR4 receptor function. In the cells that express proton-sensing GPCRs, including GPR4, OGR1, TDAG8, and G2A, extracellular acidification stimulates serum responsive element (SRE)-driven transcriptional activity, which has been shown to reflect Rho activity, with different proton sensitivities. Imidazopyridine compounds inhibited the moderately acidic pH-induced SRE activity only in GPR4-expressing cells. Acidic pH-stimulated cAMP accumulation, mRNA expression of inflammatory genes, and GPR4 internalization within GPR4-expressing cells were all inhibited by the GPR4 modulator. We further compared the inhibition property of the imidazopyridine compound with psychosine, which has been shown to selectively inhibit actions induced by proton-sensing GPCRs, including GPR4. In the GPR4 mutant, in which certain histidine residues were mutated to phenylalanine, proton sensitivity was significantly shifted to the right, and psychosine failed to further inhibit acidic pH-induced SRE activation. On the other hand, the imidazopyridine compound almost completely inhibited acidic pH-induced action in mutant GPR4. We conclude that some imidazopyridine compounds show specificity to GPR4 as negative allosteric modulators with a different action mode from psychosine, an antagonist susceptible to histidine residues, and are useful for characterizing GPR4-mediated acidic pH-induced biological actions. PMID:26070068

Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses.

PubMed

Tobo, Ayaka; Tobo, Masayuki; Nakakura, Takashi; Ebara, Masashi; Tomura, Hideaki; Mogi, Chihiro; Im, Dong-Soon; Murata, Naoya; Kuwabara, Atsushi; Ito, Saki; Fukuda, Hayato; Arisawa, Mitsuhiro; Shuto, Satoshi; Nakaya, Michio; Kurose, Hitoshi; Sato, Koichi; Okajima, Fumikazu

2015-01-01

G protein-coupled receptor 4 (GPR4), previously proposed as the receptor for sphingosylphosphorylcholine, has recently been identified as the proton-sensing G protein-coupled receptor (GPCR) coupling to multiple intracellular signaling pathways, including the Gs protein/cAMP and G13 protein/Rho. In the present study, we characterized some imidazopyridine compounds as GPR4 modulators that modify GPR4 receptor function. In the cells that express proton-sensing GPCRs, including GPR4, OGR1, TDAG8, and G2A, extracellular acidification stimulates serum responsive element (SRE)-driven transcriptional activity, which has been shown to reflect Rho activity, with different proton sensitivities. Imidazopyridine compounds inhibited the moderately acidic pH-induced SRE activity only in GPR4-expressing cells. Acidic pH-stimulated cAMP accumulation, mRNA expression of inflammatory genes, and GPR4 internalization within GPR4-expressing cells were all inhibited by the GPR4 modulator. We further compared the inhibition property of the imidazopyridine compound with psychosine, which has been shown to selectively inhibit actions induced by proton-sensing GPCRs, including GPR4. In the GPR4 mutant, in which certain histidine residues were mutated to phenylalanine, proton sensitivity was significantly shifted to the right, and psychosine failed to further inhibit acidic pH-induced SRE activation. On the other hand, the imidazopyridine compound almost completely inhibited acidic pH-induced action in mutant GPR4. We conclude that some imidazopyridine compounds show specificity to GPR4 as negative allosteric modulators with a different action mode from psychosine, an antagonist susceptible to histidine residues, and are useful for characterizing GPR4-mediated acidic pH-induced biological actions.

Prediction of LDEF exposure to the ionizing radiation environment

NASA Technical Reports Server (NTRS)

Watts, J. W.; Armstrong, T. W.; Colborn, B. L.

1996-01-01

Predictions of the LDEF mission's trapped proton and electron and galactic cosmic ray proton exposures have been made using the currently accepted models with improved resolution near mission end and better modeling of solar cycle effects. An extension of previous calculations, to provide a more definitive description of the LDEF exposure to ionizing radiation, is represented by trapped proton and electron flux as a function of mission time, presented considering altitude and solar activity variation during the mission and the change in galactic cosmic ray proton flux over the mission. Modifications of the AP8MAX and AP8MIN fluence led to a reduction of fluence by 20%. A modified interpolation model developed by Daly and Evans resulted in 30% higher dose and activation levels, which better agreed with measured values than results predicted using the Vette model.

NMR Crystallography of a Carbanionic Intermediate in Tryptophan Synthase: Chemical Structure, Tautomerization, and Reaction Specificity.

PubMed

Caulkins, Bethany G; Young, Robert P; Kudla, Ryan A; Yang, Chen; Bittbauer, Thomas J; Bastin, Baback; Hilario, Eduardo; Fan, Li; Marsella, Michael J; Dunn, Michael F; Mueller, Leonard J

2016-11-23

Carbanionic intermediates play a central role in the catalytic transformations of amino acids performed by pyridoxal-5'-phosphate (PLP)-dependent enzymes. Here, we make use of NMR crystallography-the synergistic combination of solid-state nuclear magnetic resonance, X-ray crystallography, and computational chemistry-to interrogate a carbanionic/quinonoid intermediate analogue in the β-subunit active site of the PLP-requiring enzyme tryptophan synthase. The solid-state NMR chemical shifts of the PLP pyridine ring nitrogen and additional sites, coupled with first-principles computational models, allow a detailed model of protonation states for ionizable groups on the cofactor, substrates, and nearby catalytic residues to be established. Most significantly, we find that a deprotonated pyridine nitrogen on PLP precludes formation of a true quinonoid species and that there is an equilibrium between the phenolic and protonated Schiff base tautomeric forms of this intermediate. Natural bond orbital analysis indicates that the latter builds up negative charge at the substrate C α and positive charge at C4' of the cofactor, consistent with its role as the catalytic tautomer. These findings support the hypothesis that the specificity for β-elimination/replacement versus transamination is dictated in part by the protonation states of ionizable groups on PLP and the reacting substrates and underscore the essential role that NMR crystallography can play in characterizing both chemical structure and dynamics within functioning enzyme active sites.

NMR Crystallography of a Carbanionic Intermediate in Tryptophan Synthase: Chemical Structure, Tautomerization, and Reaction Specificity

PubMed Central

2016-01-01

Carbanionic intermediates play a central role in the catalytic transformations of amino acids performed by pyridoxal-5′-phosphate (PLP)-dependent enzymes. Here, we make use of NMR crystallography—the synergistic combination of solid-state nuclear magnetic resonance, X-ray crystallography, and computational chemistry—to interrogate a carbanionic/quinonoid intermediate analogue in the β-subunit active site of the PLP-requiring enzyme tryptophan synthase. The solid-state NMR chemical shifts of the PLP pyridine ring nitrogen and additional sites, coupled with first-principles computational models, allow a detailed model of protonation states for ionizable groups on the cofactor, substrates, and nearby catalytic residues to be established. Most significantly, we find that a deprotonated pyridine nitrogen on PLP precludes formation of a true quinonoid species and that there is an equilibrium between the phenolic and protonated Schiff base tautomeric forms of this intermediate. Natural bond orbital analysis indicates that the latter builds up negative charge at the substrate Cα and positive charge at C4′ of the cofactor, consistent with its role as the catalytic tautomer. These findings support the hypothesis that the specificity for β-elimination/replacement versus transamination is dictated in part by the protonation states of ionizable groups on PLP and the reacting substrates and underscore the essential role that NMR crystallography can play in characterizing both chemical structure and dynamics within functioning enzyme active sites. PMID:27779384

Determination of the active volumes of solid-state photon-beam dosimetry detectors using the PTB proton microbeam.

PubMed

Poppinga, Daniela; Delfs, Bjoern; Meyners, Jutta; Langner, Frank; Giesen, Ulrich; Harder, Dietrich; Poppe, Bjoern; Looe, Hui K

2018-05-04

This study aims at the experimental determination of the diameters and thicknesses of the active volumes of solid-state photon-beam detectors for clinical dosimetry. The 10 MeV proton microbeam of the PTB (Physikalisch-Technische Bundesanstalt, Braunschweig) was used to examine two synthetic diamond detectors, type microDiamond (PTW Freiburg, Germany), and the silicon detectors Diode E (PTW Freiburg, Germany) and Razor Diode (Iba Dosimetry, Germany). The knowledge of the dimensions of their active volumes is essential for their Monte Carlo simulation and their applications in small-field photon-beam dosimetry. The diameter of the active detector volume was determined from the detector current profile recorded by radially scanning the proton microbeam across the detector. The thickness of the active detector volume was determined from the detector's electrical current, the number of protons incident per time interval and their mean stopping power in the active volume. The mean energy of the protons entering this volume was assessed by comparing the measured and the simulated influence of the thickness of a stack of aluminum preabsorber foils on the detector signal. For all detector types investigated, the diameters measured for the active volume closely agreed with the manufacturers' data. For the silicon Diode E detector, the thickness determined for the active volume agreed with the manufacturer's data, while for the microDiamond detectors and the Razor Diode, the thicknesses measured slightly exceeded those stated by the manufacturers. The PTB microbeam facility was used to analyze the diameters and thicknesses of the active volumes of photon dosimetry detectors for the first time. A new method of determining the thickness values with an uncertainty of ±10% was applied. The results appear useful for further consolidating detailed geometrical knowledge of the solid-state detectors investigated, which are used in clinical small-field photon-beam dosimetry. © 2018 American Association of Physicists in Medicine.

Benchmarking of a treatment planning system for spot scanning proton therapy: Comparison and analysis of robustness to setup errors of photon IMRT and proton SFUD treatment plans of base of skull meningioma

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

Harding, R., E-mail: ruth.harding2@wales.nhs.uk; Trnková, P.; Lomax, A. J.

Purpose: Base of skull meningioma can be treated with both intensity modulated radiation therapy (IMRT) and spot scanned proton therapy (PT). One of the main benefits of PT is better sparing of organs at risk, but due to the physical and dosimetric characteristics of protons, spot scanned PT can be more sensitive to the uncertainties encountered in the treatment process compared with photon treatment. Therefore, robustness analysis should be part of a comprehensive comparison between these two treatment methods in order to quantify and understand the sensitivity of the treatment techniques to uncertainties. The aim of this work was tomore » benchmark a spot scanning treatment planning system for planning of base of skull meningioma and to compare the created plans and analyze their robustness to setup errors against the IMRT technique. Methods: Plans were produced for three base of skull meningioma cases: IMRT planned with a commercial TPS [Monaco (Elekta AB, Sweden)]; single field uniform dose (SFUD) spot scanning PT produced with an in-house TPS (PSI-plan); and SFUD spot scanning PT plan created with a commercial TPS [XiO (Elekta AB, Sweden)]. A tool for evaluating robustness to random setup errors was created and, for each plan, both a dosimetric evaluation and a robustness analysis to setup errors were performed. Results: It was possible to create clinically acceptable treatment plans for spot scanning proton therapy of meningioma with a commercially available TPS. However, since each treatment planning system uses different methods, this comparison showed different dosimetric results as well as different sensitivities to setup uncertainties. The results confirmed the necessity of an analysis tool for assessing plan robustness to provide a fair comparison of photon and proton plans. Conclusions: Robustness analysis is a critical part of plan evaluation when comparing IMRT plans with spot scanned proton therapy plans.« less

Proton Induced X-Ray Emission (PIXE): Determining the Concentration of Samples

NASA Astrophysics Data System (ADS)

McCarthy, Mallory; Rodriguez Manso, Alis; Pajouhafsar, Yasmin; J Yennello, Sherry

2017-09-01

We used Proton Induced X-ray Emission (PIXE) as an analysis technique to determine the composition of samples, in particular, the elemental constituents and the concentrations. Each of the samples are bombarded with protons, which in result displaces a lower level electron and causes a higher level electron to fall into its place. This displacement produces characteristic x-rays that are `fingerprints' for each element. The protons supplied for the bombardment are produced and accelerated by the K150 proton beam in the Cyclotron Institute at Texas A&M University. The products are detected by three x-ray detectors: XR-100CR Si-PIN, XR-100SDD, and XR-100T CdTe. The peaks of the spectrum are analyzed using a software analysis tool, GUPIXWIN, to determine the concentration of the known elements of each particular sample. The goals of this work are to test run the Proton Induced X-Ray Emission experimental set up at Texas A&M University (TAMU) and to determine the concentration of thin films containing KBr given by the TAMU Chemical Engineering Department.

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

Gaubas, E., E-mail: eugenijus.gaubas@ff.vu.lt; Ceponis, T.; Jasiunas, A.

Evolution of the microwave-probed photoconductivity transients and of the proton induced luminescence has simultaneously been examined in polycrystalline CdS layers evaporated in vacuum during exposure to a 1.6 MeV proton beam. The decrease of the intensity of luminescence peaked at 510 and 709 nm wavelengths and of values of the effective carrier lifetime has been correlated in dependence of proton irradiation fluence. The defect introduction rate has been evaluated by the comparative analysis of the laser and proton beam induced luminescence. The difference of a carrier pair generation mechanism inherent for light and for a proton beam has been revealed.

Exact solution of equations for proton localization in neutron star matter

NASA Astrophysics Data System (ADS)

Kubis, Sebastian; Wójcik, Włodzimierz

2015-11-01

The rigorous treatment of proton localization phenomenon in asymmetric nuclear matter is presented. The solution of proton wave function and neutron background distribution is found by the use of the extended Thomas-Fermi approach. The minimum of energy is obtained in the Wigner-Seitz approximation of a spherically symmetric cell. The analysis of four different nuclear models suggests that the proton localization is likely to take place in the interior of a neutron star.

Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood.

PubMed

Hirano, Emi; Fuji, Hiroshi; Onoe, Tsuyoshi; Kumar, Vinay; Shirato, Hiroki; Kawabuchi, Koichi

2014-03-01

The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood. We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy. The risks of hearing loss were calculated on cochlear dose for each treatment. Three types of health-related quality of life (HRQOL) of EQ-5D, HUI3 and SF-6D were used for estimation of quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for proton beam therapy compared with X-ray radiotherapy was calculated for each HRQOL. Sensitivity analyses were performed to model uncertainty in these parameters. The ICER for EQ-5D, HUI3 and SF-6D were $21 716/QALY, $11 773/QALY, and $20 150/QALY, respectively. One-way sensitivity analyses found that the results were sensitive to discount rate, the risk of hearing loss after proton therapy, and costs of proton irradiation. Cost-effectiveness acceptability curve analysis revealed a 99% probability of proton therapy being cost effective at a societal willingness-to-pay value. Proton beam therapy with cochlear dose reduction improves health outcomes at a cost that is within the acceptable cost-effectiveness range from the payer's standpoint.

Mars proton aurora: energy deposition and Lyman-α line profile

NASA Astrophysics Data System (ADS)

Gérard, JC; Hubert, B.; Bisikalo, D. V.; Shematovich, V. I.

2017-09-01

Enhancements of the Lyman-alpha dayglow have been occasionally observed with IUVS on board MAVEN during periods of increased solar wind activity. They are interpreted as signatures of the penetration of energetic protons and H atoms into the Martian atmosphere. We present the results of Monte Carlo simulations of the energy deposition of the proton/H atom beam and the subsequent Lyman-alpha emission. We compare the observed brightness and the altitude of the emission peak with those calculated based on in-situ measurements of the incident energetic protons.

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.

Proton scattering by short lived sulfur isotopes

NASA Astrophysics Data System (ADS)

Maréchal, F.; Suomijärvi, T.; Blumenfeld, Y.; Azhari, A.; Bauge, E.; Bazin, D.; Brown, J. A.; Cottle, P. D.; Delaroche, J. P.; Fauerbach, M.; Girod, M.; Glasmacher, T.; Hirzebruch, S. E.; Jewell, J. K.; Kelley, J. H.; Kemper, K. W.; Mantica, P. F.; Morrissey, D. J.; Riley, L. A.; Scarpaci, J. A.; Scheit, H.; Steiner, M.

1999-09-01

Elastic and inelastic proton scattering has been measured in inverse kinematics on the unstable nucleus 40S. A phenomenological distorted wave Born approximation analysis yields a quadrupole deformation parameter β2=0.35+/-0.05 for the 2+1 state. Consistent phenomenological and microscopic proton scattering analyses have been applied to all even-even sulfur isotopes from A=32 to A=40. The second analysis used microscopic collective model densities and a modified Jeukenne-Lejeune-Mahaux nucleon-nucleon effective interaction. This microscopic analysis suggests the presence of a neutron skin in the heavy sulfur isotopes. The analysis is consistent with normalization values for λv and λw of 0.95 for both the real and imaginary parts of the Jeukenne-Lejeune-Mahaux potential.

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.

Abscisic acid accumulation modulates auxin transport in the root tip to enhance proton secretion for maintaining root growth under moderate water stress.

PubMed

Xu, Weifeng; Jia, Liguo; Shi, Weiming; Liang, Jiansheng; Zhou, Feng; Li, Qianfeng; Zhang, Jianhua

2013-01-01

Maintenance of root growth is essential for plant adaptation to soil drying. Here, we tested the hypothesis that auxin transport is involved in mediating ABA's modulation by activating proton secretion in the root tip to maintain root growth under moderate water stress. Rice and Arabidopsis plants were raised under a hydroponic system and subjected to moderate water stress (-0.47 MPa) with polyethylene glycol (PEG). ABA accumulation, auxin transport and plasma membrane H(+)-ATPase activity at the root tip were monitored in addition to the primary root elongation and root hair density. We found that moderate water stress increases ABA accumulation and auxin transport in the root apex. Additionally, ABA modulation is involved in the regulation of auxin transport in the root tip. The transported auxin activates the plasma membrane H(+)-ATPase to release more protons along the root tip in its adaption to moderate water stress. The proton secretion in the root tip is essential in maintaining or promoting primary root elongation and root hair development under moderate water stress. These results suggest that ABA accumulation modulates auxin transport in the root tip, which enhances proton secretion for maintaining root growth under moderate water stress. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Nonadiabatic rate constants for proton transfer and proton-coupled electron transfer reactions in solution: Effects of quadratic term in the vibronic coupling expansion

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

Soudackov, Alexander; Hammes-Schiffer, Sharon

2015-11-17

Rate constant expressions for vibronically nonadiabatic proton transfer and proton-coupled electron transfer reactions are presented and analyzed. The regimes covered include electronically adiabatic and nonadiabatic reactions, as well as high-frequency and low-frequency regimes for the proton donor-acceptor vibrational mode. These rate constants differ from previous rate constants derived with the cumulant expansion approach in that the logarithmic expansion of the vibronic coupling in terms of the proton donor-acceptor distance includes a quadratic as well as a linear term. The analysis illustrates that inclusion of this quadratic term does not significantly impact the rate constants derived using the cumulant expansion approachmore » in any of the regimes studied. The effects of the quadratic term may become significant when using the vibronic coupling expansion in conjunction with a thermal averaging procedure for calculating the rate constant, however, particularly at high temperatures and for proton transfer interfaces with extremely soft proton donor-acceptor modes that are associated with extraordinarily weak hydrogen bonds. Even with the thermal averaging procedure, the effects of the quadratic term for weak hydrogen-bonding systems are less significant for more physically realistic models that prevent the sampling of unphysical short proton donor-acceptor distances, and the expansion of the coupling can be avoided entirely by calculating the couplings explicitly for the range of proton donor-acceptor distances. This analysis identifies the regimes in which each rate constant expression is valid and thus will be important for future applications to proton transfer and proton-coupled electron transfer in chemical and biological processes. We are grateful for support from National Institutes of Health Grant GM056207 (applications to enzymes) and the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences (applications to molecular electrocatalysts).« less

Ligand versus metal protonation of an iron hydrogenase active site mimic.

PubMed

Eilers, Gerriet; Schwartz, Lennart; Stein, Matthias; Zampella, Giuseppe; de Gioia, Luca; Ott, Sascha; Lomoth, Reiner

2007-01-01

The protonation behavior of the iron hydrogenase active-site mimic [Fe2(mu-adt)(CO)4(PMe3)2] (1; adt=N-benzyl-azadithiolate) has been investigated by spectroscopic, electrochemical, and computational methods. The combination of an adt bridge and electron-donating phosphine ligands allows protonation of either the adt nitrogen to give [Fe2(mu-Hadt)(CO)4(PMe3)2]+ ([1 H]+), the Fe-Fe bond to give [Fe2(mu-adt)(mu-H)(CO)4(PMe3)2]+ ([1 Hy]+), or both sites simultaneously to give [Fe2(mu-Hadt)(mu-H)(CO)4(PMe3)2]2+ ([1 HHy]2 +). Complex 1 and its protonation products have been characterized in acetonitrile solution by IR, (1)H, and (31)P NMR spectroscopy. The solution structures of all protonation states feature a basal/basal orientation of the phosphine ligands, which contrasts with the basal/apical structure of 1 in the solid state. Density functional calculations have been performed on all protonation states and a comparison between calculated and experimental spectra confirms the structural assignments. The ligand protonated complex [1 H]+ (pKa=12) is the initial, metastable protonation product while the hydride [1 Hy]+ (pKa=15) is the thermodynamically stable singly protonated form. Tautomerization of cation [1 H]+ to [1 Hy]+ does not occur spontaneously. However, it can be catalyzed by HCl (k=2.2 m(-1) s(-1)), which results in the selective formation of cation [1 Hy]+. The protonations of the two basic sites have strong mutual effects on their basicities such that the hydride (pK(a)=8) and the ammonium proton (pK(a)=5) of the doubly protonated cationic complex [1 HHy]2+ are considerably more acidic than in the singly protonated analogues. The formation of dication [1 HHy]2+ from cation [1 H]+ is exceptionally slow with perchloric or trifluoromethanesulfonic acid (k=0.15 m(-1) s(-1)), while the dication is formed substantially faster (k>10(2) m(-1) s(-1)) with hydrobromic acid. Electrochemically, 1 undergoes irreversible reduction at -2.2 V versus ferrocene, and this potential shifts to -1.6, -1.1, and -1.0 V for the cationic complexes [1 H]+, [1 Hy]+, and [1 HHy]2+, respectively, upon protonation. The doubly protonated form [1 HHy]2+ is reduced at less negative potential than all previously reported hydrogenase models, although catalytic proton reduction at this potential is characterized by slow turnover.

Solid state linear dichroic infrared spectral analysis of benzimidazoles and their N 1-protonated salts

NASA Astrophysics Data System (ADS)

Ivanova, B. B.

2005-11-01

A stereo structural characterization of 2,5,6-thrimethylbenzimidazole (MBIZ) and 2-amino-benzimidaziole (2-NH 2-BI) and their N 1 protonation salts was carried out using a polarized solid state linear dichroic infrared spectral (IR-LD) analysis in nematic liquid crystal suspension. All experimental predicted structures were compared with the theoretical ones, obtained by ab initio calculations. The Cs to C2v* symmetry transformation as a result of protonation processes, with a view of its reflection on the infrared spectral characteristics was described.

Electromagnetic Cyclotron Waves in the Solar Wind: Wind Observation and Wave Dispersion Analysis

NASA Technical Reports Server (NTRS)

Jian, L. K.; Moya, P. S.; Vinas, A. F.; Stevens, M.

2016-01-01

Wind observed long-lasting electromagnetic cyclotron waves near the proton cyclotron frequency on 11 March 2005, in the descending part of a fast wind stream. Bi-Maxwellian velocity distributions are fitted for core protons, beam protons, and alpha-particles. Using the fitted plasma parameters we conduct kinetic linear dispersion analysis and find ion cyclotron and/or firehose instabilities grow in six of 10 wave intervals. After Doppler shift, some of the waves have frequency and polarization consistent with observation, thus may be correspondence to the cyclotron waves observed.

Electromagnetic cyclotron waves in the solar wind: Wind observation and wave dispersion analysis

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

Jian, L. K., E-mail: lan.jian@nasa.gov; Heliophysics Science Division, NASA Goddard Space Flight Center, Greenbelt, MD 20771; Moya, P. S.

2016-03-25

Wind observed long-lasting electromagnetic cyclotron waves near the proton cyclotron frequency on 11 March 2005, in the descending part of a fast wind stream. Bi-Maxwellian velocity distributions are fitted for core protons, beam protons, and α-particles. Using the fitted plasma parameters we conduct kinetic linear dispersion analysis and find ion cyclotron and/or firehose instabilities grow in six of 10 wave intervals. After Doppler shift, some of the waves have frequency and polarization consistent with observation, thus may be correspondence to the cyclotron waves observed.

Structural, thermal, morphological and biological studies of proton-transfer complexes formed from 4-aminoantipyrine with quinol and picric acid

NASA Astrophysics Data System (ADS)

Adam, Abdel Majid A.

2013-03-01

4-Aminoantipyrine (4AAP) is widely used in the pharmaceutical industry, biochemical experiments and environmental monitoring. However, residual amounts of 4AAP in the environment may pose a threat to human health. To provide basic data that can be used to extract or eliminate 4AAP from the environment, the proton-transfer complexes of 4AAP with quinol (QL) and picric acid (PA) were synthesized and spectroscopically investigated. The interactions afforded two new proton-transfer salts named 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-aminium-4-hydroxyphenolate and 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-aminium-2,4,6-trinitrophenolate for QL and PA, respectively, via a 1:1 stoichiometry. Elemental analysis (CHN), electronic absorption, spectrophotometric titration, IR, Raman, 1H NMR and X-ray diffraction were used to characterize the new products. The thermal stability of the synthesized CT complexes was investigated using thermogravimetric (TG) analyses, and the morphology and particle size of these complexes were obtained from scanning electron microscopy (SEM). It was found that PA and 4AAP immediately formed a yellow precipitate with a remarkable sponge-like morphology and good thermal stability up to 180 °C. Finally, the biological activities of the newly synthesized CT complexes were tested for their antibacterial and antifungal activities. The results indicated that the [(4AAP)(QL)] complex exhibited strong antimicrobial activities against various bacterial and fungal strains compared with standard drugs.

Structural, thermal, morphological and biological studies of proton-transfer complexes formed from 4-aminoantipyrine with quinol and picric acid.

PubMed

Adam, Abdel Majid A

2013-03-01

4-Aminoantipyrine (4AAP) is widely used in the pharmaceutical industry, biochemical experiments and environmental monitoring. However, residual amounts of 4AAP in the environment may pose a threat to human health. To provide basic data that can be used to extract or eliminate 4AAP from the environment, the proton-transfer complexes of 4AAP with quinol (QL) and picric acid (PA) were synthesized and spectroscopically investigated. The interactions afforded two new proton-transfer salts named 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-aminium-4-hydroxyphenolate and 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-aminium-2,4,6-trinitrophenolate for QL and PA, respectively, via a 1:1 stoichiometry. Elemental analysis (CHN), electronic absorption, spectrophotometric titration, IR, Raman, (1)H NMR and X-ray diffraction were used to characterize the new products. The thermal stability of the synthesized CT complexes was investigated using thermogravimetric (TG) analyses, and the morphology and particle size of these complexes were obtained from scanning electron microscopy (SEM). It was found that PA and 4AAP immediately formed a yellow precipitate with a remarkable sponge-like morphology and good thermal stability up to 180°C. Finally, the biological activities of the newly synthesized CT complexes were tested for their antibacterial and antifungal activities. The results indicated that the [(4AAP)(QL)] complex exhibited strong antimicrobial activities against various bacterial and fungal strains compared with standard drugs. Copyright © 2012 Elsevier B.V. All rights reserved.

Analysis and verification of a prediction model of solar energetic proton events

NASA Astrophysics Data System (ADS)

Wang, J.; Zhong, Q.

2017-12-01

The solar energetic particle event can cause severe radiation damages near Earth. The alerts and summary products of the solar energetic proton events were provided by the Space Environment Prediction Center (SEPC) according to the flux of the greater than 10 MeV protons taken by GOES satellite in geosynchronous orbit. The start of a solar energetic proton event is defined as the time when the flux of the greater than 10 MeV protons equals or exceeds 10 proton flux units (pfu). In this study, a model was developed to predict the solar energetic proton events, provide the warning for the solar energetic proton events at least minutes in advance, based on both the soft X-ray flux and integral proton flux taken by GOES. The quality of the forecast model was measured against verifications of accuracy, reliability, discrimination capability, and forecast skills. The peak flux and rise time of the solar energetic proton events in the six channels, >1MeV, >5 MeV, >10 MeV, >30 MeV, >50 MeV, >100 MeV, were also simulated and analyzed.

Proton Content and Nature in Perovskite Ceramic Membranes for Medium Temperature Fuel Cells and Electrolysers

PubMed Central

Colomban, Philippe; Zaafrani, Oumaya; Slodczyk, Aneta

2012-01-01

Recent interest in environmentally friendly technology has promoted research on green house gas-free devices such as water steam electrolyzers, fuel cells and CO2/syngas converters. In such applications, proton conducting perovskite ceramics appear especially promising as electrolyte membranes. Prior to a successful industrial application, it is necessary to determine/understand their complex physical and chemical behavior, especially that related to proton incorporation mechanism, content and nature of bulk protonic species. Based on the results of quasi-elastic neutron scattering (QNS), thermogravimetric analysis (TGA), Raman and IR measurements we will show the complexity of the protonation process and the importance of differentiation between the protonic species adsorbed on a membrane surface and the bulk protons. The bulk proton content is very low, with a doping limit (~1–5 × 10−3 mole/mole), but sufficient to guarantee proton conduction below 600 °C. The bulk protons posses an ionic, covalent bond free nature and may occupy an interstitial site in the host perovskite structure. PMID:24958293

Crystal Structure of Phosphatidylglycerophosphatase (PGPase), a Putative Membrane-Bound Lipid Phosphatase, Reveals a Novel Binuclear Metal Binding Site and Two Proton Wires

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

Kumaran,D.; Bonnano, J.; Burley, S.

2006-01-01

Phosphatidylglycerophosphatase (PGPase), an enzyme involved in lipid metabolism, catalyzes formation of phosphatidylglycerol from phosphatidylglycerophosphate. Phosphatidylglycerol is a multifunctional phospholipid, found in the biological membranes of many organisms. Here, we report the crystal structure of Listeria monocytogenes PGPase at 1.8 Angstroms resolution. PGPase, an all-helical molecule, forms a homotetramer. Each protomer contains an independent active site with two metal ions, Ca{sup 2+} and Mg{sup 2+}, forming a hetero-binuclear center located in a hydrophilic cavity near the surface of the molecule. The binuclear center, conserved ligands, metal-bound water molecules, and an Asp-His dyad form the active site. The catalytic mechanism of thismore » enzyme is likely to proceed via binuclear metal activated nucleophilic water. The binuclear metal-binding active-site environment of this structure should provide insights into substrate binding and metal-dependent catalysis. A long channel with inter-linked linear water chains, termed 'proton wires', is observed at the tetramer interface. Comparison of similar water chain structures in photosynthetic reaction centers (RCs), Cytochrome f, gramicidin, and bacteriorhodopsin, suggests that PGPase may conduct protons via proton wires.« less

Proton therapy detector studies under the experience gained at the CATANA facility

NASA Astrophysics Data System (ADS)

Cuttone, G.; Cirrone, G. A. P.; Di Rosa, F.; Lojacono, P. A.; Lo Nigro, S.; Marino, C.; Mongelli, V.; Patti, I. V.; Pittera, S.; Raffaele, L.; Russo, G.; Sabini, M. G.; Salamone, V.; Valastro, L. M.

2007-10-01

Proton therapy represents the most promising radiotherapy technique for external tumor treatments. At Laboratori Nazionali del Sud of the Istituto Nazionale di Fisica Nucleare (INFN-LNS), Catania (I), a proton therapy facility is active since March 2002 and 140 patients, mainly affected by choroidal and iris melanoma, have been successfully treated. Proton beams are characterized by higher dose gradients and linear energy transfer with respect to the conventional photon and electron beams, commonly used in medical centers for radiotherapy.In this paper, we report the experience gained in the characterization of different dosimetric systems, studied and/or developed during the last ten years in our proton therapy facility.

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

Wang, Xia; Wang, Yanlong; Silver, Mark A.

An ultrahigh proton conductivity of 2.91 × 10 −2 S cm −1 and an ultralow activation energy of 0.10 eV were observed in an anionic lanthanide-organic framework. Both values approach the records for proton-conducting MOF materials.

Statistical Prediction of Solar Particle Event Frequency based on the Measurements of Recent Solar Cycles for Acute Radiation Risk Analysis

NASA Astrophysics Data System (ADS)

Kim, M. Y.; Hu, S.; Cucinotta, F. A.

2009-12-01

Large solar particle events (SPEs) present significant acute radiation risks to the crew members during extra-vehicular activities (EVAs) or in lightly shielded space vehicles for space missions beyond the protection of the Earth’s magnetic field. Acute radiation sickness (ARS) can impair performance and result in failure of the mission. Improved forecasting capability and/or early-warning systems and proper shielding solutions are required to stay within NASA’s short-term dose limits. Exactly how to make use of observations of SPEs for predicting occurrence and size is a great challenge, because SPE occurrences themselves are random in nature even though the expected frequency of SPEs is strongly influenced by the time position within the solar activity cycle. Therefore, we developed a probabilistic model approach, where a cumulative expected occurrence curve of SPEs for a typical solar cycle was formed from a non-homogeneous Poisson process model fitted to a database of proton fluence measurements of SPEs that occurred during the past 5 solar cycles (19 -23) and those of large SPEs identified from impulsive nitrate enhancements in polar ice. From the fitted model, the expected frequency of SPEs was estimated at any given proton fluence threshold (ΦE) with energy (E) >30 MeV during a defined space mission period. Corresponding ΦE (E=30, 60, and 100 MeV) fluence distributions were simulated with a random draw from a gamma distribution, and applied for SPE ARS risk analysis for a specific mission period. It has been found that the accurate prediction of deep-seated organ doses was more precisely predicted at high energies, Φ100, than at lower energies such as Φ30 or Φ60, because of the high penetration depth of high energy protons. Estimates of ARS are then described for 90th and 95th percentile events for several mission lengths and for several likely organ dose-rates. The ability to accurately measure high energy protons (50-300 MeV) in real-time is shown to be a crucial issue for crew protection.

Statistical Prediction of Solar Particle Event Frequency Based on the Measurements of Recent Solar Cycles for Acute Radiation Risk Analysis

NASA Technical Reports Server (NTRS)

Myung-Hee, Y. Kim; Shaowen, Hu; Cucinotta, Francis A.

2009-01-01

Large solar particle events (SPEs) present significant acute radiation risks to the crew members during extra-vehicular activities (EVAs) or in lightly shielded space vehicles for space missions beyond the protection of the Earth's magnetic field. Acute radiation sickness (ARS) can impair performance and result in failure of the mission. Improved forecasting capability and/or early-warning systems and proper shielding solutions are required to stay within NASA's short-term dose limits. Exactly how to make use of observations of SPEs for predicting occurrence and size is a great challenge, because SPE occurrences themselves are random in nature even though the expected frequency of SPEs is strongly influenced by the time position within the solar activity cycle. Therefore, we developed a probabilistic model approach, where a cumulative expected occurrence curve of SPEs for a typical solar cycle was formed from a non-homogeneous Poisson process model fitted to a database of proton fluence measurements of SPEs that occurred during the past 5 solar cycles (19 - 23) and those of large SPEs identified from impulsive nitrate enhancements in polar ice. From the fitted model, the expected frequency of SPEs was estimated at any given proton fluence threshold (Phi(sub E)) with energy (E) >30 MeV during a defined space mission period. Corresponding Phi(sub E) (E=30, 60, and 100 MeV) fluence distributions were simulated with a random draw from a gamma distribution, and applied for SPE ARS risk analysis for a specific mission period. It has been found that the accurate prediction of deep-seated organ doses was more precisely predicted at high energies, Phi(sub 100), than at lower energies such as Phi(sub 30) or Phi(sub 60), because of the high penetration depth of high energy protons. Estimates of ARS are then described for 90th and 95th percentile events for several mission lengths and for several likely organ dose-rates. The ability to accurately measure high energy protons (50-300 MeV) in real-time is shown to be a crucial issue for crew protection.

Structural and Electrochemical Consequences of [Cp*] Ligand Protonation.

PubMed

Peng, Yun; Ramos-Garcés, Mario V; Lionetti, Davide; Blakemore, James D

2017-09-05

There are few examples of the isolation of analogous metal complexes bearing [η 5 -Cp*] and [η 4 -Cp*H] (Cp* = pentamethylcyclopentadienyl) complexes within the same metal/ligand framework, despite the relevance of such structures to catalytic applications. Recently, protonation of Cp*Rh(bpy) (bpy = 2,2'-bipyridyl) has been shown to yield a complex bearing the uncommon [η 4 -Cp*H] ligand, rather than generating a [Rh III -H] complex. We now report the purification and isolation of this protonated species, as well as characterization of analogous complexes of 1,10-phenanthroline (phen). Specifically, reaction of Cp*Rh(bpy) or Cp*Rh(phen) with 1 equiv of Et 3 NH + Br - affords rhodium compounds bearing endo-η 4 -pentamethylcyclopentadiene (η 4 -Cp*H) as a ligand. NMR spectroscopy and single-crystal X-ray diffraction studies confirm protonation of the Cp* ligand, rather than formation of metal hydride complexes. Analysis of new structural data and electronic spectra suggests that phen is significantly reduced in Cp*Rh(phen), similar to the case of Cp*Rh(bpy). Backbonding interactions with olefinic motifs are activated by formation of [η 4 -Cp*H]; protonation of [Cp*] stabilizes the low-valent metal center and results in loss of reduced character on the diimine ligands. In accord with these changes in electronic structure, electrochemical studies reveal a distinct manifold of redox processes that are accessible in the [Cp*H] complexes in comparison with their [Cp*] analogues; these processes suggest new applications in catalysis for the complexes bearing endo-η 4 -Cp*H.

Photosynthetic dioxygen formation studied by time-resolved delayed fluorescence measurements--method, rationale, and results on the activation energy of dioxygen formation.

PubMed

Buchta, Joachim; Grabolle, Markus; Dau, Holger

2007-06-01

The analysis of the time-resolved delayed fluorescence (DF) measurements represents an important tool to study quantitatively light-induced electron transfer as well as associated processes, e.g. proton movements, at the donor side of photosystem II (PSII). This method can provide, inter alia, insights in the functionally important inner-protein proton movements, which are hardly detectable by conventional spectroscopic approaches. The underlying rationale and experimental details of the method are described. The delayed emission of chlorophyll fluorescence of highly active PSII membrane particles was measured in the time domain from 10 mus to 60 ms after each flash of a train of nanosecond laser pulses. Focusing on the oxygen-formation step induced by the third flash, we find that the recently reported formation of an S4-intermediate prior to the onset of O-O bond formation [M. Haumann, P. Liebisch, C. Müller, M. Barra, M. Grabolle, H. Dau, Science 310, 1019-1021, 2006] is a multiphasic process, as anticipated for proton movements from the manganese complex of PSII to the aqueous bulk phase. The S4-formation involves three or more likely sequential steps; a tri-exponential fit yields time constants of 14, 65, and 200 mus (at 20 degrees C, pH 6.4). We determine that S4-formation is characterized by a sizable difference in Gibbs free energy of more than 90 meV (20 degrees C, pH 6.4). In the second part of the study, the temperature dependence (-2.7 to 27.5 degrees C) of the rate constant of dioxygen formation (600/s at 20 degrees C) was investigated by analysis of DF transients. If the activation energy is assumed to be temperature-independent, a value of 230 meV is determined. There are weak indications for a biphasicity in the Arrhenius plot, but clear-cut evidence for a temperature-dependent switch between two activation energies, which would point to the existence of two distinct rate-limiting steps, is not obtained.

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

Cirrone, G. A. P.; Cuttone, G.; Di Rosa, F.

After six years of activity 155 patients have been treated inside the CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) facility. CATANA is the first and unique proton therapy facility in which the 62 MeV proton beams, accelerated by a Superconducting Cyclotron, are used for the radio-therapeutic treatments of choroidal and iris melanomas. Inside CATANA new absolute and relative dosimetric techniques have been developed in order to achieve the best results in terms of treatment precision and dose release accuracy. The follow-up results for 42 patients demonstrated the efficacy of high energy protons in the radiotherapeutic field and encouraged usmore » in our activity in the battle against cancer.« less

Proton irradiation impacts age-driven modulations of cancer progression influenced by immune system transcriptome modifications from splenic tissue.

PubMed

Wage, Justin; Ma, Lili; Peluso, Michael; Lamont, Clare; Evens, Andrew M; Hahnfeldt, Philip; Hlatky, Lynn; Beheshti, Afshin

2015-09-01

Age plays a crucial role in the interplay between tumor and host, with additional impact due to irradiation. Proton irradiation of tumors induces biological modulations including inhibition of angiogenic and immune factors critical to 'hallmark' processes impacting tumor development. Proton irradiation has also provided promising results for proton therapy in cancer due to targeting advantages. Additionally, protons may contribute to the carcinogenesis risk from space travel (due to the high proportion of high-energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice was altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68-day) versus old (736-day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5 Gy (1-GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared with older subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74 and RUVBL2 indicated these were the key genes involved in the regulatory changes in the host environment response (i.e. the spleen). Collectively, these results suggest that a significant biological component of proton irradiation is modulated by host age through promotion of carcinogenesis in adolescence and resistance to immunosuppression, carcinogenesis and genetic perturbation associated with advancing age. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Activation cross-section measurement of proton induced reactions on cerium

NASA Astrophysics Data System (ADS)

Tárkányi, F.; Hermanne, A.; Ditrói, F.; Takács, S.; Spahn, I.; Spellerberg, S.

2017-12-01

In the framework of a systematic study of proton induced nuclear reactions on lanthanides we have measured the excitation functions on natural cerium for the production of 142,139,138m,137Pr, 141,139,137m,137g,135Ce and 133La up to 65 MeV proton energy using the activation method with stacked-foil irradiation technique and high-resolution γ-ray spectrometry. The cross-sections of the investigated reactions were compared with the data retrieved from the TENDL-2014 and TENDL-2015 libraries, based on the latest version of the TALYS code system. No earlier experimental data were found in the literature. The measured cross-section data are important for further improvement of nuclear reaction models and for practical applications in nuclear medicine, other labeling and activation studies.

On-line catalogs of solar energetic protons at SRTI-BAS

NASA Astrophysics Data System (ADS)

Miteva, R.; Danov, D.

2017-08-01

We outline the status of the on-line catalogs of solar energetic particles supported by the Space Climate group at the Space Research and Technology, Bulgarian Academy of Sciences (SRTI-BAS). In addition to the already compiled proton catalog from Wind/EPACT instrument, in the current report we present preliminary results on the high energy SOHO/ERNE proton enhancement identifications as well as comparative analysis with two other proton lists. The future plans for the on-line catalogs are briefly summarized.

TOR complex 1 regulates the yeast plasma membrane proton pump and pH and potassium homeostasis.

PubMed

Mahmoud, Shima; Planes, María Dolores; Cabedo, Marc; Trujillo, Cristina; Rienzo, Alessandro; Caballero-Molada, Marcos; Sharma, Sukesh C; Montesinos, Consuelo; Mulet, José Miguel; Serrano, Ramón

2017-07-01

We have identified in yeast a connection between two master regulators of cell growth: a biochemical connection involving the TORC1 protein kinase (which activates protein synthesis, nutrient uptake, and anabolism) and a biophysical connection involving the plasma membrane proton-pumping H + -ATPase Pma1 (which drives nutrient and K + uptake and regulates pH homeostasis). Raising the temperature to nonpermissive values in a TOR thermosensitive mutant decreases Pma1 activity. Rapamycin, a TORC1 inhibitor, inhibits Pma1 dependent on its receptor Fpr1 and on the protein phosphatase Sit4, a TORC1 effector. Mutation of either Sit4 or Tco89, a nonessential subunit of TORC1, decreases proton efflux, K + uptake, intracellular pH, cell growth, and tolerance to weak organic acids. Tco89 does not affect Pma1 activity but activates K + transport. © 2017 Federation of European Biochemical Societies.

Alkaline and non-aqueous proton-conducting pouch-cell batteries

DOEpatents

Young, Kwo-hsiung; Nei, Jean; Meng, Tiejun

2018-01-02

Provided are sealed pouch-cell batteries that are alkaline batteries or non-aqueous proton-conducing batteries. A pouch cell includes a flexible housing such as is used for pouch cell construction where the housing is in the form of a pouch, a cathode comprising a cathode active material suitable for use in an alkaline battery, an anode comprising an anode active material suitable for use in an alkaline battery, an electrolyte that is optionally an alkaline or proton-conducting electrolyte, and wherein the pouch does not include or require a safety vent or other gas absorbing or releasing system as the anode active material and the cathode active material do not increase the internal atmospheric pressure any more than 2 psig during cycling. The batteries provided function contrary to the art recognized belief that such battery systems were impossible due to unacceptable gas production during cycling.

EFFECT OF CHERENKOV LIGHT POLARIZATION ON TOTAL REFLECTION COUNTER

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

Dowell, J.D.; Duteil, P.; Leontic, B.

1963-01-01

A rugged total internal reflection counter with a 3- to 5cm thick compact radiator was used at the CERN proton synchrotron for beam analysis. The threshold behavior of this counter was compared when filled with glycerol and with turpentine. Turpentine is optically active and rotates the plane of polarization about 7 un. Concent 85% /cm. Figures illustrate the effect of this polarization rotation. (A.G.W.)

Coastal Benthic Boundary Layer (CBBL) Research Program: A review of the fourth year

DTIC Science & Technology

1998-09-01

followed by manganese oxide, nitrate , iron oxides, and sulfate. Some of these reactions produce protons, which promote the dissolution of carbonate...investigated. Specific activities during FY97 include: (1) continued multiscale analysis of Eckernförde sediments with inclusions of Key West...certain bacteria can then mediate organic matter oxidation (and obtain energy in the process) using nitrate as the terminal electron acceptor rather than

Two Mechanisms Involved in Trigeminal CGRP Release: Implications for Migraine Treatment

PubMed Central

Durham, Paul L.; Masterson, Caleb G.

2012-01-01

Objective The goal of this study was to better understand the cellular mechanisms involved in proton stimulation of calcitonin gene-related peptide (CGRP) secretion from cultured trigeminal neurons by investigating the effects of two anti-migraine therapies, onabotulinumtoxin A and rizatriptan. Background Stimulated CGRP release from peripheral and central terminating processes of trigeminal ganglia neurons is implicated in migraine pathology by promoting inflammation and nociception. Based on models of migraine pathology, several inflammatory molecules including protons are thought to facilitate sensitization and activation of trigeminal nociceptive neurons and stimulate CGRP secretion. Despite the reported efficacy of triptans and onabotulinumtoxinA to treat acute and chronic migraine, respectively, a substantial number of migraneurs do not get adequate relief with these therapies. A possible explanation is that triptans and onabutulinumtoxinA are not able to block proton mediated CGRP secretion. Methods CGRP secretion from cultured primary trigeminal ganglia neurons was quantitated by radioimmunoassay while intracellular calcium and sodium levels were measured in neurons via live cell imaging using Fura2-AM and SBFI-AM, respectively. The expression of ASIC3 was determined by immunocytochemistry and western blot analysis. In addition, the involvement of ASICs in mediating proton stimulation of CGRP was investigated using the potent and selective ASIC3 inhibitor APETx2. Results While KCl caused a significant increase in CGRP secretion that was significantly repressed by treatment with EGTA, onabotulinumtoxinA, and rizatriptan, the stimulatory effect of protons (pH 5.5) was not suppressed by EGTA, onabotulinumtoxinA, or rizatriptan. In addition, while KCl caused a transient increase in intracellular calcium levels that was blocked by EGTA, no appreciable change in calcium levels was observed with proton treatment. However, protons did significantly increase the intracellular level of sodium ions. Under our culture conditions, ASIC3 was shown to be expressed in most trigeminal ganglion neurons. Importantly, proton stimulation of CGRP secretion was repressed by pretreatment with the ASIC3 inhibitor APETx2, but not the TRPV1 antagonist capsazepine. Conclusions Our findings provide evidence that proton regulated release of CGRP from trigeminal neurons utilizes a different mechanism than the calcium and SNAP-25 dependent pathways that are inhibited by the anti-migraine therapies rizatriptan and onabotulinumtoxinA. PMID:23095108

Space Environment Information System (SPENVIS)

NASA Astrophysics Data System (ADS)

Kruglanski, M.; Messios, N.; de Donder, E.; Gamby, E.; Calders, S.; Hetey, L.; Evans, H.

2009-04-01

SPENVIS is an ESA operational software developed and maintained at BIRA-IASB since 1996. It provides standardized access to most of the recent models of the hazardous space environment, through a user-friendly Web interface (http://www.spenvis.oma.be/). The system allows spacecraft engineers to perform a rapid analysis of environmental problems related to natural radiation belts, solar energetic particles, cosmic rays, plasmas, gases, magnetic fields and micro-particles. Various reporting and graphical utilities and extensive help facilities are included to allow engineers with relatively little familiarity to produce reliable results. SPENVIS also contains an active, integrated version of the ECSS Space Environment Standard and access to in-flight data on the space environment. Although SPENVIS in the first place is designed to help spacecraft engineers, it is also used by technical universities in their educational programs. At present more than 4000 users are registered. With SPENVIS, one can generate a spacecraft trajectory or a coordinate grid and then calculate: geomagnetic coordinates; trapped proton and electron fluxes; solar proton fluences; cosmic ray fluxes; radiation doses (ionising and non-ionising) for simple geometries; a sectoring analysis for dose calculations in more complex geometries; damage equivalent fluences for Si, GaAs and multi-junction solar cells; Geant4 Monte Carlo analysis for doses and pulse height rates in planar and spherical shields; ion LET and flux spectra and single event upset rates; trapped proton flux anisotropy; atmospheric and ionospheric densities and temperatures; atomic oxygen erosion depths; surface and internal charging characteristics; solar array current collections and power losses; wall damage. The new version of SPENVIS (to be released in January 2009) also allows mission analysis for Mars and Jupiter.

In-depth analysis of the substorm recovery phase using electron and proton induced emissions from satellite observations

NASA Astrophysics Data System (ADS)

Bryant, Chad Richard

The aurora is a well known phenomenon in the night sky. The observer of the ground can only see part of what is truly happening. The active aurora observed from the ground relates in many cases to what is termed a magnetospheric substorm. Recent research has been involved in determining the cause of these events while other parts of the substorm have been little studied. While additional progress will be made through conventional analysis and observations of the substorm onset, new approaches are advantageous to clarify different aspects of magnetospheric substorms. Very little quantitative analysis has been completed on what is called the recovery phase. This dissertation represents an attempt to achieve the first in-depth quantitative study of the recovery phase. It will use conventional electron auroral observations as well as an exceptional new dataset courtesy of global images of proton aurora. To effectively exploit the observations, new analysis tools were developed to expand our understanding of the recovery phase. In this dissertation the use of the auroral substorm power was determined to be a good analytical method in working with magnetospheric substorms. The start and end of the recovery phase and the decay of the recovery phase were all analysed using this methodology. It was found that the decay of the recovery phase is exponential but can be interrupted by enhancements that are related to flows in the magnetotail and that the region from where the flow comes determines the optical signature that is seen in the ionosphere. An example shows how the unique proton dataset provides new possibilities for observations when compared to conventional electron auroral observations. All of these results provide valuable new insights into current magnetospheric substorm models.

The effect of boron on plasma membrane electron transport and associated proton secretion by cultured carrot cells.

PubMed

Barr, R; Böttger, M; Crane, F L

1993-09-01

Plasma membrane electron transport reactions and associated proton secretion were studied in boron-deficient carrot cells. It was found that the hormone-sensitive plasma membrane NADH oxidase was inhibited by boron deficiency and that under such conditions activity could be restored by exogenous boric acid with or without 2,4-dichlorophenoxy acetic acid. Gramicidin, a channel-forming protonophore, further stimulated NADH oxidase by carrot cells. Proton secretion, associated with plasma membrane H(+)-ATPase, was also affected by boron deficiency, but not as severely as ferricyanide-generated proton secretion, reflecting plasma membrane electron transport. The addition of 1 mM boric acid and 1 microM 2,4-dichlorophenoxy acetic acid to carrot cells fully restored the H+ secretion in presence of ferricyanide. The effect of boron deficiency in cultured carrot cells can, therefore, be directly associated with cell growth through its effect on the plasma membrane NADH oxidase and H+ secretion. Ferricyanide provides a probe which activates transmembrane electron transport that is only coupled to proton release when boron is present.

MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential

PubMed Central

Sun, Chao; Liu, Xiongxiong; Di, Cuixia; Wang, Zhenhua; Mi, Xiangquan; Liu, Yang; Zhao, Qiuyue; Mao, Aihong; Chen, Weiqiang; Gan, Lu; Zhang, Hong

2017-01-01

ABSTRACT During the process of oxidative phosphorylation, protons are pumped into the mitochondrial intermembrane space to establish a mitochondrial membrane potential (MMP). The electrochemical gradient generated allows protons to return to the matrix through the ATP synthase complex and generates ATP in the process. MitoQ is a lipophilic cationic drug that is adsorbed to the inner mitochondrial membrane; however, the cationic moiety of MitoQ remains in the intermembrane space. We found that the positive charges in MitoQ inhibited the activity of respiratory chain complexes I, III, and IV, reduced proton production, and decreased oxygen consumption. Therefore, a pseudo-MMP (PMMP) was formed via maintenance of exogenous positive charges. Proton backflow was severely impaired, leading to a decrease in ATP production and an increase in AMP production. Excess AMP activates AMP kinase, which inhibits the MTOR (mechanistic target of rapamycin) pathway and induces macroautophagy/autophagy. Therefore, we conclude that MitoQ increases PMMP via proton displacement with exogenous positive charges. In addition, PMMP triggered autophagy in hepatocellular carcinoma HepG2 cells via modification of mitochondrial bioenergetics pathways. PMID:28121478

MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential.

PubMed

Sun, Chao; Liu, Xiongxiong; Di, Cuixia; Wang, Zhenhua; Mi, Xiangquan; Liu, Yang; Zhao, Qiuyue; Mao, Aihong; Chen, Weiqiang; Gan, Lu; Zhang, Hong

2017-04-03

During the process of oxidative phosphorylation, protons are pumped into the mitochondrial intermembrane space to establish a mitochondrial membrane potential (MMP). The electrochemical gradient generated allows protons to return to the matrix through the ATP synthase complex and generates ATP in the process. MitoQ is a lipophilic cationic drug that is adsorbed to the inner mitochondrial membrane; however, the cationic moiety of MitoQ remains in the intermembrane space. We found that the positive charges in MitoQ inhibited the activity of respiratory chain complexes I, III, and IV, reduced proton production, and decreased oxygen consumption. Therefore, a pseudo-MMP (PMMP) was formed via maintenance of exogenous positive charges. Proton backflow was severely impaired, leading to a decrease in ATP production and an increase in AMP production. Excess AMP activates AMP kinase, which inhibits the MTOR (mechanistic target of rapamycin) pathway and induces macroautophagy/autophagy. Therefore, we conclude that MitoQ increases PMMP via proton displacement with exogenous positive charges. In addition, PMMP triggered autophagy in hepatocellular carcinoma HepG2 cells via modification of mitochondrial bioenergetics pathways.

Novel insights into the bioenergetics of mixed-acid fermentation: can hydrogen and proton cycles combine to help maintain a proton motive force?

PubMed

Trchounian, Armen; Gary Sawers, R

2014-01-01

Escherichia coli possesses four [NiFe]-hydrogenases that catalyze the reversible redox reaction of 2H(+) + 2e(-) ↔ H2. These enzymes together have the potential to form a hydrogen cycle across the membrane. Their activity, operational direction, and interaction with each other depend on the fermentation substrate and particularly pH. The enzymes producing H2 are likely able to translocate protons through the membrane. Moreover, the activity of some of these enzymes is dependent on the F0 F1 -ATPase, thus linking a proton cycle with the cycling of hydrogen. These two cycles are suggested to have a primary basic role in modulating the cell's energetics during mixed-acid fermentation, particularly in response to pH. Nevertheless, the mechanisms underlying the physical interactions between these enzyme complexes, as well as how this is controlled, are still not clearly understood. Here, we present a synopsis of the potential impact of proton-hydrogen cycling in fermentative bioenergetics. © 2013 International Union of Biochemistry and Molecular Biology.

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

Proton exchange membrane fuel cells for space and electric vehicle applications: From basic research to technology development

NASA Technical Reports Server (NTRS)

Srinivasan, Supramaniam; Mukerjee, Sanjeev; Parthasarathy, A.; CesarFerreira, A.; Wakizoe, Masanobu; Rho, Yong Woo; Kim, Junbom; Mosdale, Renaut A.; Paetzold, Ronald F.; Lee, James

1994-01-01

The proton exchange membrane fuel cell (PEMFC) is one of the most promising electrochemical power sources for space and electric vehicle applications. The wide spectrum of R&D activities on PEMFC's, carried out in our Center from 1988 to date, is as follows (1) Electrode Kinetic and Electrocatalysis of Oxygen Reduction; (2) Optimization of Structures of Electrodes and of Membrane and Electrode Assemblies; (3) Selection and Evaluation of Advanced Proton Conducting Membranes and of Operating Conditions to Attain High Energy Efficiency; (4) Modeling Analysis of Fuel Cell Performance and of Thermal and Water Management; and (5) Engineering Design and Development of Multicell Stacks. The accomplishments on these tasks may be summarized as follows: (1) A microelectrode technique was developed to determine the electrode kinetic parameters for the fuel cell reactions and mass transport parameters for the H2 and O2 reactants in the proton conducting membrane. (2) High energy efficiencies and high power densities were demonstrated in PEMFCs with low platinum loading electrodes (0.4 mg/cm(exp 2) or less), advanced membranes and optimized structures of membrane and electrode assemblies, as well as operating conditions. (3) The modeling analyses revealed methods to minimize mass transport limitations, particularly with air as the cathodic reactant; and for efficient thermal and water management. (4) Work is in progress to develop multi-kilowatt stacks with the electrodes containing low platinum loadings.

An analysis of the impact of LHC Run I proton-lead data on nuclear parton densities.

PubMed

Armesto, Néstor; Paukkunen, Hannu; Penín, José Manuel; Salgado, Carlos A; Zurita, Pía

2016-01-01

We report on an analysis of the impact of available experimental data on hard processes in proton-lead collisions during Run I at the large hadron collider on nuclear modifications of parton distribution functions. Our analysis is restricted to the EPS09 and DSSZ global fits. The measurements that we consider comprise production of massive gauge bosons, jets, charged hadrons and pions. This is the first time a study of nuclear PDFs includes this number of different observables. The goal of the paper is twofold: (i) checking the description of the data by nPDFs, as well as the relevance of these nuclear effects, in a quantitative manner; (ii) testing the constraining power of these data in eventual global fits, for which we use the Bayesian reweighting technique. We find an overall good, even too good, description of the data, indicating that more constraining power would require a better control over the systematic uncertainties and/or the proper proton-proton reference from LHC Run II. Some of the observables, however, show sizeable tension with specific choices of proton and nuclear PDFs. We also comment on the corresponding improvements as regards the theoretical treatment.

A Simple Geometric Model for the Marcus Theory of Proton Transfer

ERIC Educational Resources Information Center

McLennan, Duncan J.

1976-01-01

Uses the intersecting parabola model to derive an equation that relates the observed free energy of activation for a slow proton transfer to the overall thermodynamic free energy change in the reaction. (MLH)

Preparation of high specific activity technetium-96

DOEpatents

Mausner, Leonard F.; Srivastava, Suresh C.; Prach, Thomas

1992-01-01

The present invention relates to a method of producing Tc-96 from the proton irradiation of a rhodium target and a technique for isolating under remote hot cell conditions the Tc-96 from the proton irradiated target.

Z-H Bond Activation in (Di)hydrogen Bonding as a Way to Proton/Hydride Transfer and H2 Evolution.

PubMed

Belkova, Natalia V; Filippov, Oleg A; Shubina, Elena S

2018-02-01

The ability of neutral transition-metal hydrides to serve as a source of hydride ion H - or proton H + is well appreciated. The hydride ligands possessing a partly negative charge are proton accepting sites, forming a dihydrogen bond, M-H δ- ⋅⋅⋅ δ+ HX (M=transition metal or metalloid). On the other hand, some metal hydrides are able to serve as a proton source and give hydrogen bond of M-H δ+ ⋅⋅⋅X type (X=organic base). In this paper we analyse recent works on transition-metal and boron hydrides showing i) how formation of an intermolecular complex between the reactants changes the Z-H (M-H and X-H) bond polarity and ii) what is the implication of such activation in the mechanisms of hydrides reactions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

PTR-MS in Italy: A Multipurpose Sensor with Applications in Environmental, Agri-Food and Health Science

PubMed Central

Cappellin, Luca; Loreto, Francesco; Aprea, Eugenio; Romano, Andrea; del Pulgar, José Sánchez; Gasperi, Flavia; Biasioli, Franco

2013-01-01

Proton Transfer Reaction Mass Spectrometry (PTR-MS) has evolved in the last decade as a fast and high sensitivity sensor for the real-time monitoring of volatile compounds. Its applications range from environmental sciences to medical sciences, from food technology to bioprocess monitoring. Italian scientists and institutions participated from the very beginning in fundamental and applied research aiming at exploiting the potentialities of this technique and providing relevant methodological advances and new fundamental indications. In this review we describe this activity on the basis of the available literature. The Italian scientific community has been active mostly in food science and technology, plant physiology and environmental studies and also pioneered the applications of the recently released PTR-ToF-MS (Proton Transfer Reaction-Time of Flight-Mass Spectrometry) in food science and in plant physiology. In the very last years new results related to bioprocess monitoring and health science have been published as well. PTR-MS data analysis, particularly in the case of the ToF based version, and the application of advanced chemometrics and data mining are also aspects characterising the activity of the Italian community. PMID:24021966

Production of Hydroxyl Radical via the Activation of Hydrogen Peroxide by Hydroxylamine.

PubMed

Chen, Liwei; Li, Xuchun; Zhang, Jing; Fang, Jingyun; Huang, Yanmin; Wang, Ping; Ma, Jun

2015-09-01

The production of the hydroxyl radical (HO·) is important in environmental chemistry. This study reports a new source of HO· generated solely from hydrogen peroxide (H2O2) activated by hydroxylamine (HA). Electron paramagnetic resonance analysis and the oxidation of a HO· probe, benzoic acid, were used to confirm the production of HO·. The production of HO· increased with increasing concentrations of either HA or H2O2 as well as decreasing pH. The second-order rate constant for the reaction was (2.2 ± 0.2) × 10(-4) M(-1) s(-1). HO· was probably produced in two steps: the activation of H2O2 by protonated HA and then reaction between the H2O2 and the intermediate protonated aminoxyl radical generated in the first step. Such a two-step oxidation can possibly be ascribed to the ionizable hydroxyl moiety in the molecular structure of HA, as is suggested by comparing the reactivity of a series of HA derivatives in HO· production. The results shed light on a previously unknown source of HO· formation, which broadens the understanding of its role in environmental processes.

Determination of elemental tissue composition following proton treatment using positron emission tomography

NASA Astrophysics Data System (ADS)

Cho, Jongmin; Ibbott, Geoffrey; Gillin, Michael; Gonzalez-Lepera, Carlos; Min, Chul Hee; Zhu, Xuping; El Fakhri, Georges; Paganetti, Harald; Mawlawi, Osama

2013-06-01

Positron emission tomography (PET) has been suggested as an imaging technique for in vivo proton dose and range verification after proton induced-tissue activation. During proton treatment, irradiated tissue is activated and decays while emitting positrons. In this paper, we assessed the feasibility of using PET imaging after proton treatment to determine tissue elemental composition by evaluating the resultant composite decay curve of activated tissue. A phantom consisting of sections composed of different combinations of 1H, 12C, 14N, and 16O was irradiated using a pristine Bragg peak and a 6 cm spread-out Bragg-peak (SOBP) proton beam. The beam ranges defined at 90% distal dose were 10 cm the delivered dose was 1.6 Gy for the near monoenergetic beam and 2 Gy for the SOBP beam. After irradiation, activated phantom decay was measured using an in-room PET scanner for 30 min in list mode. Decay curves from the activated 12C and 16O sections were first decomposed into multiple simple exponential decay curves, each curve corresponding to a constituent radioisotope, using a least-squares method. The relative radioisotope fractions from each section were determined. These fractions were used to guide the decay curve decomposition from the section consisting mainly of 12C + 16O and calculate the relative elemental composition of 12C and 16O. A Monte Carlo simulation was also used to determine the elemental composition of the 12C + 16O section. The calculated compositions of the 12C + 16O section using both approaches (PET and Monte Carlo) were compared with the true known phantom composition. Finally, two patients were imaged using an in-room PET scanner after proton therapy of the head. Their PET data and the technique described above were used to construct elemental composition (12C and 16O) maps that corresponded to the proton-activated regions. We compared the 12C and 16O compositions of seven ROIs that corresponded to the vitreous humor, adipose/face mask, adipose tissue, and brain tissue with ICRU 46 elemental composition data. The 12C and 16O compositions of the 12C + 16O phantom section were estimated to within a maximum difference of 3.6% for the near monoenergetic and SOBP beams over an 8 cm depth range. On the other hand, the Monte Carlo simulation estimated the corresponding 12C and 16O compositions in the 12C + 16O section to within a maximum difference of 3.4%. For the patients, the 12C and 16O compositions in the seven ROIs agreed with the ICRU elemental composition data, with a mean (maximum) difference of 9.4% (15.2%). The 12C and 16O compositions of the phantom and patients were estimated with relatively small differences. PET imaging may be useful for determining the tissue elemental composition and thereby improving proton treatment planning and verification.

Changing hydration level in an internal cavity modulates the proton affinity of a key glutamate in cytochrome c oxidase.

PubMed

Goyal, Puja; Lu, Jianxun; Yang, Shuo; Gunner, M R; Cui, Qiang

2013-11-19

Cytochrome c oxidase contributes to the transmembrane proton gradient by removing two protons from the high-pH side of the membrane each time the binuclear center active site is reduced. One proton goes to the binuclear center, whereas the other is pumped to the low-pH periplasmic space. Glutamate 286 (Glu286) has been proposed to serve as a transiently deprotonated proton donor. Using unrestrained atomistic molecular dynamics simulations, we show that the size of and water distribution in the hydrophobic cavity that holds Glu286 is controlled by the protonation state of the propionic acid of heme a3, a group on the proton outlet pathway. Protonation of the propionate disrupts hydrogen bonding to two side chains, allowing a loop to swing open. Continuum electrostatics and atomistic free-energy perturbation calculations show that the resultant changes in hydration and electrostatic interactions lower the Glu proton affinity by at least 5 kcal/mol. These changes in the internal hydration level occur in the absence of major conformational transitions and serve to stabilize needed transient intermediates in proton transport. The trigger is not the protonation of the Glu of interest, but rather the protonation of a residue ∼10 Å away. Thus, unlike local water penetration to stabilize a new charge, this finding represents a specific role for water molecules in the protein interior, mediating proton transfers and facilitating ion transport.

Multistate empirical valence bond study of temperature and confinement effects on proton transfer in water inside hydrophobic nanochannels.

PubMed

Tahat, Amani; Martí, Jordi

2016-07-01

Microscopic characteristics of an aqueous excess proton in a wide range of thermodynamic states, from low density amorphous ices (down to 100 K) to high temperature liquids under the critical point (up to 600 K), placed inside hydrophobic graphene slabs at the nanometric scale (with interplate distances between 3.1 and 0.7 nm wide) have been analyzed by means of molecular dynamics simulations. Water-proton and carbon-proton forces were modeled with a multistate empirical valence bond method. Densities between 0.07 and 0.02 Å(-3) have been considered. As a general trend, we observed a competition between effects of confinement and temperature on structure and dynamical properties of the lone proton. Confinement has strong influence on the local structure of the proton, whereas the main effect of temperature on proton properties is observed on its dynamics, with significant variation of proton transfer rates, proton diffusion coefficients, and characteristic frequencies of vibrational motions. Proton transfer is an activated process with energy barriers between 1 and 10 kJ/mol for both proton transfer and diffusion, depending of the temperature range considered and also on the interplate distance. Arrhenius-like behavior of the transfer rates and of proton diffusion are clearly observed for states above 100 K. Spectral densities of proton species indicated that in all states Zundel-like and Eigen-like complexes survive at some extent. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Alleviation of proton toxicity by nitrate uptake specifically depends on nitrate transporter 1.1 in Arabidopsis.

PubMed

Fang, Xian Zhi; Tian, Wen Hao; Liu, Xing Xing; Lin, Xian Yong; Jin, Chong Wei; Zheng, Shao Jian

2016-07-01

Protons in acid soil are highly rhizotoxic to plants, but the mechanism of tolerance of plants to protons is largely unknown. Nitrate uptake by root cells is accompanied by the uptake of protons. Therefore, nitrate uptake transporters (NRTs) may be involved in plant tolerance to proton toxicity. We investigated the root nitrate uptake response to proton stress in Arabidopsis and its association with proton tolerance using NRT-related mutants and pharmacological methods. Lack of NRT1.1 in knockout nrt1.1 mutants led to impaired proton tolerance in nitrate-sufficient growth medium, whereas no difference was seen between wild-type plants and NRT1.2-, NRT2.1-, NRT2.2-, and NRT2.4-null mutants. Another nrt1.1 point mutant, which is defective in nitrate uptake but has a normal nitrate-sensing function, also had impaired proton tolerance compared with the wild-type plant. Furthermore, proton stress induced NRT1.1-mediated nitrate uptake. These results indicate that NRT1.1-conferred proton tolerance depends on nitrate uptake activity. In addition, the rooting medium was alkalified by wild-type plants, but not by knockout nrt1.1 mutants, and in pH-buffered medium, there were no differences in proton tolerance between wild-type plants and knockout nrt1.1 mutants. We conclude that NRT1.1-mediated nitrate uptake plays a crucial role in plant proton tolerance by alkalifying the rhizosphere. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

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

Novel dimeric bis(7)-tacrine proton-dependently inhibits NMDA-activated currents

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

Luo, Jialie; Li, Wenming; Liu, Yuwei

2007-09-21

Bis(7)-tacrine has been shown to prevent glutamate-induced neuronal apoptosis by blocking NMDA receptors. However, the characteristics of the inhibition have not been fully elucidated. In this study, we further characterize the features of bis(7)-tacrine inhibition of NMDA-activated current in cultured rat hippocampal neurons. The results show that with the increase of extracellular pH, the inhibitory effect decreases dramatically. At pH 8.0, the concentration-response curve of bis(7)-tacrine is shifted rightwards with the IC{sub 50} value increased from 0.19 {+-} 0.03 {mu}M to 0.41 {+-} 0.04 {mu}M. In addition, bis(7)-tacrine shifts the proton inhibition curve rightwards. Furthermore, the inhibitory effect of bis(7)-tacrinemore » is not altered by the presence of the NMDA receptor proton sensor shield spermidine. These results indicate that bis(7)-tacrine inhibits NMDA-activated current in a pH-dependent manner by sensitizing NMDA receptors to proton inhibition, rendering it potentially beneficial therapeutic effects under acidic conditions associated with stroke and ischemia.« 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

Reduction of α,β-Unsaturated Ketones by Old Yellow Enzymes: Mechanistic Insights from Quantum Mechanics/Molecular Mechanics Calculations.

PubMed

Lonsdale, Richard; Reetz, Manfred T

2015-11-25

Enoate reductases catalyze the reduction of activated C═C bonds with high enantioselectivity. The oxidative half-reaction, which involves the addition of a hydride and a proton to opposite faces of the C═C bond, has been studied for the first time by hybrid quantum mechanics/molecular mechanics (QM/MM). The reduction of 2-cyclohexen-1-one by YqjM from Bacillus subtilis was selected as the model system. Two-dimensional QM/MM (B3LYP-D/OPLS2005) reaction pathways suggest that the hydride and proton are added as distinct steps, with the former step preceding the latter. Furthermore, we present interesting insights into the reactivity of this enzyme, including the weak binding of the substrate in the active site, the role of the two active site histidine residues for polarization of the substrate C═O bond, structural details of the transition states to hydride and proton transfer, and the role of Tyr196 as proton donor. The information presented here will be useful for the future design of enantioselective YqjM mutants for other substrates.

Neutron Structure of Human Carbonic Anhydrase II: Implications for Proton Transfer†

PubMed Central

Fisher, S. Zoë; Kovalevsky, Andrey Y.; Domsic, John F.; Mustyakimov, Marat; McKenna, Robert; Silverman, David N.; Langan, Paul A.

2010-01-01

Human carbonic anhydrase II (HCA II) catalyzes the reversible hydration of carbon dioxide to form bicarbonate and a proton. Despite many high-resolution X-ray crystal structures, mutagenesis, and kinetic data, the structural details of the active site, especially the proton transfer pathway, are unclear. A large HCA II crystal was prepared at pH 9.0 and subjected to vapor H–D exchange to replace labile hydrogens with deuteriums. Neutron diffraction studies were conducted at the Protein Crystallography Station at Los Alamos National Laboratory. The structure to 2.0 Å resolution reveals several interesting active site features: (1) the Zn-bound solvent appearing to be predominantly a D2O molecule, (2) the orientation and hydrogen bonding pattern of solvent molecules in the active site cavity, (3) the side chain of His64 being unprotonated (neutral) and predominantly in an inward conformation pointing toward the zinc, and (4) the phenolic side chain of Tyr7 appearing to be unprotonated. The implications of these details are discussed, and a proposed mechanism for proton transfer is presented. PMID:20025241

NMR detection of pH-dependent histidine-water proton exchange reveals the conduction mechanism of a transmembrane proton channel.

PubMed

Hu, Fanghao; Schmidt-Rohr, Klaus; Hong, Mei

2012-02-29

The acid-activated proton channel formed by the influenza M2 protein is important for the life cycle of the virus. A single histidine, His37, in the M2 transmembrane domain (M2TM) is responsible for pH activation and proton selectivity of the channel. Recent studies suggested three models for how His37 mediates proton transport: a shuttle mechanism involving His37 protonation and deprotonation, a H-bonded imidazole-imidazolium dimer model, and a transporter model involving large protein conformational changes in synchrony with proton conduction. Using magic-angle-spinning (MAS) solid-state NMR spectroscopy, we examined the proton exchange and backbone conformational dynamics of M2TM in a virus-envelope-mimetic membrane. At physiological temperature and pH, (15)N NMR spectra show fast exchange of the imidazole (15)N between protonated and unprotonated states. To quantify the proton exchange rates, we measured the (15)N T(2) relaxation times and simulated them for chemical-shift exchange and fluctuating N-H dipolar fields under (1)H decoupling and MAS. The exchange rate is 4.5 × 10(5) s(-1) for Nδ1 and 1.0 × 10(5) s(-1) for Nε2, which are approximately synchronized with the recently reported imidazole reorientation. Binding of the antiviral drug amantadine suppressed both proton exchange and ring motion, thus interfering with the proton transfer mechanism. By measuring the relative concentrations of neutral and cationic His as a function of pH, we determined the four pK(a) values of the His37 tetrad in the viral membrane. Fitting the proton current curve using the charge-state populations from these pK(a)'s, we obtained the relative conductance of the five charge states, which showed that the +3 channel has the highest time-averaged unitary conductance. At physiologically relevant pH, 2D correlation spectra indicated that the neutral and cationic histidines do not have close contacts, ruling out the H-bonded dimer model. Moreover, a narrowly distributed nonideal helical structure coexists with a broadly distributed ideal helical conformation without interchange on the sub-10 ms time scale, thus excluding the transporter model in the viral membrane. These data support the shuttle mechanism of proton conduction, whose essential steps involve His-water proton exchange facilitated by imidazole ring reorientations. © 2011 American Chemical Society

Ionospheric effects of the extreme solar activity of February 1986

NASA Technical Reports Server (NTRS)

Boska, J.; Pancheva, D.

1989-01-01

During February 1986, near the minimum of the 11 year Solar sunspot cycle, after a long period of totally quiet solar activity (R sub z = 0 on most days in January) a period of a suddenly enhanced solar activity occurred in the minimum between solar cycles 21 and 22. Two proton flares were observed during this period. A few other flares, various phenomena accompanying proton flares, an extremely severe geomagnetic storm and strong disturbances in the Earth's ionosphere were observed in this period of enhanced solar activity. Two active regions appeared on the solar disc. The flares in both active regions were associated with enhancement of solar high energy proton flux which started on 4 February of 0900 UT. Associated with the flares, the magnetic storm with sudden commencement had its onset on 6 February 1312 UT and attained its maximum on 8 February (Kp = 9). The sudden enhancement in solar activity in February 1986 was accompanied by strong disturbances in the Earth's ionosphere, SIDs and ionospheric storm. These events and their effects on the ionosphere are discussed.

The R/D of high power proton accelerator technology in China

NASA Astrophysics Data System (ADS)

Xialing, Guan

2002-12-01

In China, a multipurpose verification system as a first phase of our ADS program consists of a low energy accelerator (150 MeV/3 mA proton LINAC) and a swimming pool light water subcritical reactor. In this paper the activities of HPPA technology related to ADS in China, which includes the intense proton ECR source, the RFQ accelerator and some other technology of HPPA, are described.

International Symposium on Recent Observations and Simulations of the Sun-Earth System

DTIC Science & Technology

2007-01-10

the Energy Dependence the Relative Contributions Ionospheric and Solar Sources of the Ring Current Protons Kovtyukh A.S. Skobeltsyn...heavily dependent on solar activity, are energetic solar protons of MeV range energies . Therefore, it is necessary to consider available qualitative...70 15:10–15:25 B. Lavraud, V. Jordanova: Modeling the Effects of Cold-Dense and Hot-Tenuous Plasma Sheet on Proton Ring Current Energy

Determining beam parameters in a storage ring with a cylindrical hodoscope using elastic proton proton scattering

NASA Astrophysics Data System (ADS)

Rohdjeß, H.; Albers, D.; Bisplinghoff, J.; Bollmann, R.; Büßer, K.; Diehl, O.; Dohrmann, F.; Engelhardt, H.-P.; Eversheim, P. D.; Gasthuber, M.; Greiff, J.; Groß, A.; Groß-Hardt, R.; Hinterberger, F.; Igelbrink, M.; Langkau, R.; Maier, R.; Mosel, F.; Müller, M.; Münstermann, M.; Prasuhn, D.; von Rossen, P.; Scheid, H.; Schirm, N.; Schwandt, F.; Scobel, W.; Trelle, H. J.; Wellinghausen, A.; Wiedmann, W.; Woller, K.; Ziegler, R.

2006-01-01

The EDDA-detector at the cooler-synchrotron COSY/Jülich has been operated with an internal CH2 fiber target to measure proton-proton elastic scattering differential cross-sections. For data analysis knowledge of beam parameters, like position, width and angle, are indispensable. We have developed a method to obtain these values with high precision from the azimuthal and polar angles of the ejectiles only, by exploiting the coplanarity of the two final-state protons with the beam and the kinematic correlation. The formalism is described and results for beam parameters obtained during beam acceleration are given.

Proton-Coupled Electron Transfer and Substituent Effects in Catechol-Based Deep Eutectic Solvents: Gross and Fine Tuning of Redox Activity.

PubMed

Smith, Parker J; Goeltz, John C

2017-12-07

The 1,2-diol moiety in a variety of substituted catechols allows formation of room temperature ionic melts in a 2:1 ratio with choline chloride or choline dihydrogen citrate. These deep eutectic solvents were 4.3-6.6 M in redox active catechols. Substituents on 3- and 4-substituted catechols shift both E° and pK a such that Hammett parameters predict the observed E p for oxidation in square wave voltammetry. The proton acceptor for the proton-coupled oxidation shifts the observed E p more strongly than the substituents within the substituents and acceptors reported here. The shift is predicted well by the pK a of the conjugate acid of the proton acceptor, i.e., water in aqueous solutions or chloride or dihydrogen citrate in the DESs in this study. Together, the substituent and the proton acceptor allow gross and fine-tuning of the oxidation potential for catechol over 750 mV, the first demonstration of control of the thermodynamics of proton-coupled electron transfer in deep eutectic solvents. Changing the substituents on the HBD affords fine control in tens of millivolts, while changing the base strength of the anion of the organic salt affords gross control across hundreds of millivolts.

Low-dose radiation modifies skin response to acute gamma-rays and protons.

PubMed

Mao, Xiao Wen; Pecaut, Michael J; Cao, Jeffrey D; Moldovan, Maria; Gridley, Daila S

2013-01-01

The goal of the present study was to obtain pilot data on the effects of protracted low-dose/low-dose-rate (LDR) γ-rays on the skin, both with and without acute gamma or proton irradiation (IR). Six groups of C57BL/6 mice were examined: a) 0 Gy control, b) LDR, c) Gamma, d) LDR+Gamma, e) Proton, and f) LDR+Proton. LDR radiation was delivered to a total dose of 0.01 Gy (0.03 cGy/h), whereas the Gamma and Proton groups received 2 Gy (0.9 Gy/min and 1.0 Gy/min, respectively). Assays were performed 56 days after exposure. Skin samples from all irradiated groups had activated caspase-3, indicative of apoptosis. The significant (p<0.05) increases in immunoreactivity in the Gamma and Proton groups were not present when LDR pre-exposure was included. However, the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay for DNA fragmentation and histological examination of hematoxylin and eosin-stained sections revealed no significant differences among groups, regardless of radiation regimen. The data demonstrate that caspase-3 activation initially triggered by both forms of acute radiation was greatly elevated in the skin nearly two months after whole-body exposure. In addition, LDR γ-ray priming ameliorated this response.

Persistent activation of nuclear factor-kappa B and expression of pro-inflammatory cytokines in bone marrow cells after exposure of mice to protons

NASA Astrophysics Data System (ADS)

Rithidech, Kanokporn; Reungpatthanaphong, Paiboon; Honikel, Louise; Whorton, Elbert

Protons are the most abundant component of solar particle events (SPEs) in space. Information is limited on early-and late-occurring in vivo biological effects of exposure to protons at doses and dose rates that are similar to what astronauts encounter in space. We conducted a study series to fill this knowledge gap. We focused on the biological effects of 100 MeV/n protons, which are one of the most abundant types of protons induced during SPEs. We gave BALB/cJ mice a whole-body exposure to 0.5 or 1.0 Gy of 100 MeV/n protons, delivered at 0.5 or 1.0 cGy/min. These doses and dose rates of protons were selected because they are comparable to those of SPEs taking place in space. For each dose and dose rate of 100 MeV/n protons, mice exposed to 0 Gy of protons served as sham controls. Mice included in this study were also part of a study series conducted to examine the extent and the mechanisms involved in in vivo induction of genomic instability (expressed as late-occurring chromosome instability) by 100 MeV/n protons. Bone marrow (BM) cells were collected from groups of mice for analyses at different times post-exposure, i.e. early time-points (1.5, 3, and 24 hr) and late time-points (1 and 6 months). At each harvest time, there were five mice per treatment group. Several endpoints were used to investigate the biological effects of 100 MeV/n protons in BM cells from irradiated and sham control mice. The scope of this study was to determine the dose-rate effects of 0.5 Gy of 100 MeV/n protons in BM cells on the kinetics of nuclear factor-kappa B (NF-kappa B) activation and the expression of selected NF-kappa B target proteins known to be involved in inflammatory response, i.e. pro-inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6). Significantly high levels (p values ranging from p¡0.01 and p¡0.05) of activated NF-kappa B were observed in BM cells collected from irradiated mice, relative to those obtained from the corresponding sham controls, at all time-points included in the study, regardless of the dose rate of proton-irradiation. However, these increases were more pronounced when the higher dose rate (1.0 cGy/min) was used. The results indicated that NF-kappa B activation in BM cells persisted up to 6 months after exposure of mice to a single dose of 0.5 Gy of 100 MeV/n protons, delivered at the dose rates occurring in space. Further, significantly up-regulated levels of TNF-alpha were detected in BM cells of exposed mice (p values ranging from p¡0.01 and p¡0.05), compared to those in the corresponding sham controls, at all harvest times, in spite of the difference in dose rate of proton-irradiation. However, steady increases in the levels of IL-1 beta and IL-6 in BM cells of exposed mice over the levels in their sham controls across all time-points included in the study were detected only when a dose rate of 1.0 cGy/min was used. In contrast, with a dose rate of 0.5 cGy/min, significantly high expression levels of these two pro-inflammatory cytokines were consistently found in BM cells collected from exposed mice at late time-points only. In summary, our data provide important information for space flight missions because the findings of persistent activation of NF-kappa B and expression of pro-inflammatory cytokines suggest the occurrence of chronic inflammation after exposure of mice to 100 MeV/n protons that, in turn, may have an important impact on health outcome during space flights. Knowledge gained on the NF-kappa B pathway from this study could, therefore, be useful for planning countermeasure strategies to protect astronauts or space travelers in the space environment. Research funded by NASA Grant NNX07AP88G.

Designed inhibitors with hetero linkers for gastric proton pump H+,K+-ATPase: Steered molecular dynamics and metadynamics studies.

PubMed

Jana, Kalyanashis; Bandyopadhyay, Tusar; Ganguly, Bishwajit

2017-11-01

Acid suppressant SCH28080 and its derivatives reversibly reduce acid secretion activity of the H + ,K + -ATPase in a K + competitive manner. The results on homologation of the SCH28080 by varying the linker chain length suggested the improvement in efficacy. However, the pharmacokinetic studies reveal that the hydrophobic nature of the CH 2 linker units may not help it to function as a better acid suppressant. We have exploited the role of linker unit to enhance the efficacy of such reversible acid suppressant drug molecules using hetero linker, i.e., disulfide and peroxy linkers. The logarithm of partition coefficient defined for a drug molecule relates to the partition coefficient, which allows the optimum solubility characteristics to reach the active site. The logarithm of partition coefficient calculated for the designed inhibitors suggests that inhibitors would possibly reach the active site in sufficient concentration like in the case of SCH28080. The steered molecular dynamics studies have revealed that the Inhibitor-1 with disulfide linker unit is more stable at the active site due to greater noncovalent interactions compared to the SCH28080. Centre of mass distance analysis suggests that the Cysteine-813 amino acid residue selectively plays an important role in the inhibition of H + ,K + -ATPase for Inhibitor-1. Furthermore, the quantum chemical calculations with M11L/6-31+G(d,p) level of theory have been performed to account the noncovalent interactions responsible for the stabilization of inhibitor molecules in the active site gorge of the gastric proton pump at different time scale. The hydrogen bonding and hydrophobic interaction studies corroborate the center of mass distance analysis as well. Well-tempered metadynamics free energy surface and center of mass separation analysis for the Inhibitor-1 is in good agreement with the steered molecular dynamics results. The torsional angle of the linker units seems to be crucial for better efficacy of drug molecules. The torsional angle of linker units of SCH28080 (COCH 2 C) and of Inhibitor 1 (CSSC) prefers to lie within ∼60°-90° for a longer time during the simulations, whereas, the peroxy linker (COOC) of Inhibitor 2 prefers to adopt ∼120-160°. Therefore, it appears that the smaller torsion angle of linker units can achieve better interactions with the active site residues of H + ,K + -ATPase to inhibit the acid secretion activity. The reversible drug molecules with disulfide linker unit would be a promising candidate as proton pump antagonist to H + ,K + -ATPase. Copyright © 2017 Elsevier Inc. All rights reserved.

A mechanism for the activation of the Na/H exchanger NHE-1 by cytoplasmic acidification and mitogens

PubMed Central

Lacroix, Jérôme; Poët, Mallorie; Maehrel, Céline; Counillon, Laurent

2004-01-01

Eukaryotic cells constantly have to fight against internal acidification. In mammals, this task is mainly performed by the ubiquitously expressed electroneutral Na+/H+ exchanger NHE-1, which activates in a cooperative manner when cells become acidic. Despite its biological importance, the mechanism of this activation is still poorly understood, the most commonly accepted hypothesis being the existence of a proton-sensor site on the internal face of the transporter. This work uncovers mutations that lead to a nonallosteric form of the exchanger and demonstrates that NHE-1 activation is best described by a Monod–Wyman–Changeux concerted mechanism for a dimeric transporter. During intracellular acidification, a low-affinity form of NHE-1 is converted into a form possessing a higher affinity for intracellular protons, with no requirement for an additional proton-sensor site on the protein. This new mechanism also explains the activation of the exchanger by growth signals, which shift the equilibrium towards the high-affinity form. PMID:14710192

[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.

An experimental approach to improve the Monte Carlo modelling of offline PET/CT-imaging of positron emitters induced by scanned proton beams

NASA Astrophysics Data System (ADS)

Bauer, J.; Unholtz, D.; Kurz, C.; Parodi, K.

2013-08-01

We report on the experimental campaign carried out at the Heidelberg Ion-Beam Therapy Center (HIT) to optimize the Monte Carlo (MC) modelling of proton-induced positron-emitter production. The presented experimental strategy constitutes a pragmatic inverse approach to overcome the known uncertainties in the modelling of positron-emitter production due to the lack of reliable cross-section data for the relevant therapeutic energy range. This work is motivated by the clinical implementation of offline PET/CT-based treatment verification at our facility. Here, the irradiation induced tissue activation in the patient is monitored shortly after the treatment delivery by means of a commercial PET/CT scanner and compared to a MC simulated activity expectation, derived under the assumption of a correct treatment delivery. At HIT, the MC particle transport and interaction code FLUKA is used for the simulation of the expected positron-emitter yield. For this particular application, the code is coupled to externally provided cross-section data of several proton-induced reactions. Studying experimentally the positron-emitting radionuclide yield in homogeneous phantoms provides access to the fundamental production channels. Therefore, five different materials have been irradiated by monoenergetic proton pencil beams at various energies and the induced β+ activity subsequently acquired with a commercial full-ring PET/CT scanner. With the analysis of dynamically reconstructed PET images, we are able to determine separately the spatial distribution of different radionuclide concentrations at the starting time of the PET scan. The laterally integrated radionuclide yields in depth are used to tune the input cross-section data such that the impact of both the physical production and the imaging process on the various positron-emitter yields is reproduced. The resulting cross-section data sets allow to model the absolute level of measured β+ activity induced in the investigated targets within a few per cent. Moreover, the simulated distal activity fall-off positions, representing the central quantity for treatment monitoring in terms of beam range verification, are found to agree within 0.6 mm with the measurements at different initial beam energies in both homogeneous and heterogeneous targets. Based on work presented at the Third European Workshop on Monte Carlo Treatment Planning (Seville, 15-18 May 2012).

Conductivity equations of protons transporting through 2D crystals obtained with the rate process theory and free volume concept

NASA Astrophysics Data System (ADS)

Hao, Tian; Xu, Yuanze; Hao, Ting

2018-04-01

The Eyring's rate process theory and free volume concept are employed to treat protons (or other particles) transporting through a 2D (two dimensional) crystal like graphene and hexagonal boron nitride. The protons are assumed to be activated first in order to participate conduction and the conduction rate is dependent on how much free volume available in the system. The obtained proton conductivity equations show that only the number of conduction protons, proton size and packing structure, and the energy barrier associated with 2D crystals are critical; the quantization conductance is unexpectedly predicted with a simple Arrhenius type temperature dependence. The predictions agree well with experimental observations and clear out many puzzles like much smaller energy barrier determined from experiments than from the density function calculations and isotope separation rate independent of the energy barrier of 2D crystals, etc. Our work may deepen our understandings on how protons transport through a membrane and has direct implications on hydrogen related technology and proton involved bioprocesses.

Enhanced Proton Conductivity in Y-Doped BaZrO3 via Strain Engineering.

PubMed

Fluri, Aline; Marcolongo, Aris; Roddatis, Vladimir; Wokaun, Alexander; Pergolesi, Daniele; Marzari, Nicola; Lippert, Thomas

2017-12-01

The effects of stress-induced lattice distortions (strain) on the conductivity of Y-doped BaZrO 3 , a high-temperature proton conductor with key technological applications for sustainable electrochemical energy conversion, are studied. Highly ordered epitaxial thin films are grown in different strain states while monitoring the stress generation and evolution in situ. Enhanced proton conductivity due to lower activation energies is discovered under controlled conditions of tensile strain. In particular, a twofold increased conductivity is measured at 200 °C along a 0.7% tensile strained lattice. This is at variance with conclusions coming from force-field simulations or the static calculations of diffusion barriers. Here, extensive first-principles molecular dynamic simulations of proton diffusivity in the proton-trapping regime are therefore performed and found to agree with the experiments. The simulations highlight that compressive strain confines protons in planes parallel to the substrate, while tensile strain boosts diffusivity in the perpendicular direction, with the net result that the overall conductivity is enhanced. It is indeed the presence of the dopant and the proton-trapping effect that makes tensile strain favorable for proton conduction.

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

NMR Observation of Mobile Protons in Proton-Implanted ZnO Nanorods

PubMed Central

Park, Jun Kue; Kwon, Hyeok-Jung; Lee, Cheol Eui

2016-01-01

The diffusion properties of H+ in ZnO nanorods are investigated before and after 20 MeV proton beam irradiation by using 1H nuclear magnetic resonance (NMR) spectroscopy. Herein, we unambiguously observe that the implanted protons occupy thermally unstable site of ZnO, giving rise to a narrow NMR line at 4.1 ppm. The activation barrier of the implanted protons was found to be 0.46 eV by means of the rotating-frame spin-lattice relaxation measurements, apparently being interstitial hydrogens. High-energy beam irradiation also leads to correlated jump diffusion of the surface hydroxyl group of multiple lines at ~1 ppm, implying the presence of structural disorder at the ZnO surface. PMID:26988733

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.

Proton upsets in LSI memories in space

NASA Technical Reports Server (NTRS)

Mcnulty, P. J.; Wyatt, R. C.; Filz, R. C.; Rothwell, P. L.; Farrell, G. E.

1980-01-01

Two types of large scale integrated dynamic random access memory devices were tested and found to be subject to soft errors when exposed to protons incident at energies between 18 and 130 MeV. These errors are shown to differ significantly from those induced in the same devices by alphas from an Am-241 source. There is considerable variation among devices in their sensitivity to proton-induced soft errors, even among devices of the same type. For protons incident at 130 MeV, the soft error cross sections measured in these experiments varied from 10 to the -8th to 10 to the -6th sq cm/proton. For individual devices, however, the soft error cross section consistently increased with beam energy from 18-130 MeV. Analysis indicates that the soft errors induced by energetic protons result from spallation interactions between the incident protons and the nuclei of the atoms comprising the device. Because energetic protons are the most numerous of both the galactic and solar cosmic rays and form the inner radiation belt, proton-induced soft errors have potentially serious implications for many electronic systems flown in space.

Proton-coupled electron transfer and the role of water molecules in proton pumping by cytochrome c oxidase

PubMed Central

Sharma, Vivek; Enkavi, Giray; Vattulainen, Ilpo; Róg, Tomasz; Wikström, Mårten

2015-01-01

Molecular oxygen acts as the terminal electron sink in the respiratory chains of aerobic organisms. Cytochrome c oxidase in the inner membrane of mitochondria and the plasma membrane of bacteria catalyzes the reduction of oxygen to water, and couples the free energy of the reaction to proton pumping across the membrane. The proton-pumping activity contributes to the proton electrochemical gradient, which drives the synthesis of ATP. Based on kinetic experiments on the O–O bond splitting transition of the catalytic cycle (A → PR), it has been proposed that the electron transfer to the binuclear iron–copper center of O2 reduction initiates the proton pump mechanism. This key electron transfer event is coupled to an internal proton transfer from a conserved glutamic acid to the proton-loading site of the pump. However, the proton may instead be transferred to the binuclear center to complete the oxygen reduction chemistry, which would constitute a short-circuit. Based on atomistic molecular dynamics simulations of cytochrome c oxidase in an explicit membrane–solvent environment, complemented by related free-energy calculations, we propose that this short-circuit is effectively prevented by a redox-state–dependent organization of water molecules within the protein structure that gates the proton transfer pathway. PMID:25646428

Imaging an optogenetic pH sensor reveals that protons mediate lateral inhibition in the retina.

PubMed

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

2014-02-01

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

Role of pendant proton relays and proton-coupled electron transfer on the hydrogen evolution reaction by nickel hangman porphyrins

DOE PAGES

Bediako, D. Kwabena; Solis, Brian H.; Dogutan, Dilek K.; ...

2014-10-08

Here, the hangman motif provides mechanistic insights into the role of pendant proton relays in governing proton-coupled electron transfer (PCET) involved in the hydrogen evolution reaction (HER). We now show improved HER activity of Ni compared with Co hangman porphyrins. Cyclic voltammogram data and simulations, together with computational studies using density functional theory, implicate a shift in electrokinetic zone between Co and Ni hangman porphyrins due to a change in the PCET mechanism. Unlike the Co hangman porphyrin, the Ni hangman porphyrin does not require reduction to the formally metal(0) species before protonation by weak acids in acetonitrile. We concludemore » that protonation likely occurs at the Ni(I) state followed by reduction, in a stepwise proton transfer–electron transfer pathway. Spectroelectrochemical and computational studies reveal that upon reduction of the Ni(II) compound, the first electron is transferred to a metal-based orbital, whereas the second electron is transferred to a molecular orbital on the porphyrin ring.« less

Role of pendant proton relays and proton-coupled electron transfer on the hydrogen evolution reaction by nickel hangman porphyrins

PubMed Central

Bediako, D. Kwabena; Solis, Brian H.; Dogutan, Dilek K.; Roubelakis, Manolis M.; Maher, Andrew G.; Lee, Chang Hoon; Chambers, Matthew B.; Hammes-Schiffer, Sharon; Nocera, Daniel G.

2014-01-01

The hangman motif provides mechanistic insights into the role of pendant proton relays in governing proton-coupled electron transfer (PCET) involved in the hydrogen evolution reaction (HER). We now show improved HER activity of Ni compared with Co hangman porphyrins. Cyclic voltammogram data and simulations, together with computational studies using density functional theory, implicate a shift in electrokinetic zone between Co and Ni hangman porphyrins due to a change in the PCET mechanism. Unlike the Co hangman porphyrin, the Ni hangman porphyrin does not require reduction to the formally metal(0) species before protonation by weak acids in acetonitrile. We conclude that protonation likely occurs at the Ni(I) state followed by reduction, in a stepwise proton transfer–electron transfer pathway. Spectroelectrochemical and computational studies reveal that upon reduction of the Ni(II) compound, the first electron is transferred to a metal-based orbital, whereas the second electron is transferred to a molecular orbital on the porphyrin ring. PMID:25298534

Gene expression profiling of breast cancer cell lines treated with proton and electron radiations.

PubMed

Bravatà, Valentina; Minafra, Luigi; Cammarata, Francesco Paolo; Pisciotta, Pietro; Lamia, Debora; Marchese, Valentina; Manti, Lorenzo; Cirrone, Giuseppe Ap; Gilardi, Maria Carla; Cuttone, Giacomo; Forte, Giusi Irma; Russo, Giorgio

2018-06-11

Technological advances in radiation therapy are evolving with the use of hadrons, such as protons, indicated for tumors where conventional radiotherapy does not give significant advantages or for tumors located in sensitive regions, which need the maximum of dose-saving of the surrounding healthy tissues. The genomic response to conventional and non conventional Linear Energy Transfer exposure is a poor investigated topic and became an issue of radiobiological interest. The aim of this work was to analyze and compare molecular responses in term of gene expression profiles, induced by electron and proton irradiation in breast cancer cell lines. We studied the gene expression profiling differences by cDNA microarray activated in response to electron and proton irradiation with different Linear Energy Transfer values, among three breast cell lines (the tumorigenic MCF7 and MDA-MB-231 and the non tumorigenic MCF10A), exposed to the same sub-lethal dose of 9 Gy. Gene expression profiling pathway analyses showed the activation of different signaling and molecular networks in a cell line and radiation type-dependent manner. MCF10A and MDA-MB-231 cell lines were found to induce factors and pathways involved in the immunological process control. Here we describe in a detailed way the gene expression profiling and pathways activated after electron and proton irradiation in breast cancer cells. Summarizing, although specific pathways are activated in a radiation type-dependent manner, each cell line activates overall similar molecular networks in response to both these two types of ionizing radiation. Advances in knowledge: In the era of personalized medicine and breast cancer target-directed intervention, we trust that this study could drive radiation therapy towards personalized treatments, evaluating possible combined treatments, based on the molecular characterization.

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

Spitznagel, D

Purpose: The use of protons for radiation therapy is growing rapidly. One consequence of protons interacting with different media is activation. These nuclear reactions induced by the protons, scattered neutrons, and gamma rays, activate different materials encountered, particularly by the therapists. The purpose of this study was to examine the derived nuclides from the activation, and also the decay rate. Methods: The study was conducted in our proton therapy facility. Protons are derived from a synchrocyclotron and pass through field shipping systems, apertures, and range compensators to define the beam within the patient.Included materials of concerns measured; the patient supportmore » couch, sheet rock in the wall, solid plastics used for quality assurance and dosimetry, and the passive scattering system itself, which includes brass apertures, and Lucite or blue wax compensators. All devices were studied post irradiation using gamma spectroscopy to determine the nuclides, and a sodium iodine scintillation detector to measure decay, particularly when the dose rate fell to background levels. Results: We have also determined from the measurements we will maintain brass apertures for three months before sending them for scrap. Some of the radionuclides arrived from these measurements included Na-22 for the blue wax compensator, C1-34m for the sheetrock, and Sc-44 and Co-60 for the brass apertures. We found compensators made out of Lucite or wax decayed to background in 2 hours. The patient support couch decayed to background in approximately 40 minutes, and sheet rock decayed in 80 minutes. In terms of the aperture layers, the most proximal aperture slab had much higher activity than the distal slab. Also the proximal sides of the slabs were much more activate than the distal. Conclusion: We have given proper instruction to therapists performing quality assurance in terms of the handled plastics, and to handle apertures rapidly as possible.« less

Interpretation of pH-activity profiles for acid-base catalysis from molecular simulations.

PubMed

Dissanayake, Thakshila; Swails, Jason M; Harris, Michael E; Roitberg, Adrian E; York, Darrin M

2015-02-17

The measurement of reaction rate as a function of pH provides essential information about mechanism. These rates are sensitive to the pK(a) values of amino acids directly involved in catalysis that are often shifted by the enzyme active site environment. Experimentally observed pH-rate profiles are usually interpreted using simple kinetic models that allow estimation of "apparent pK(a)" values of presumed general acid and base catalysts. One of the underlying assumptions in these models is that the protonation states are uncorrelated. In this work, we introduce the use of constant pH molecular dynamics simulations in explicit solvent (CpHMD) with replica exchange in the pH-dimension (pH-REMD) as a tool to aid in the interpretation of pH-activity data of enzymes and to test the validity of different kinetic models. We apply the methods to RNase A, a prototype acid-base catalyst, to predict the macroscopic and microscopic pK(a) values, as well as the shape of the pH-rate profile. Results for apo and cCMP-bound RNase A agree well with available experimental data and suggest that deprotonation of the general acid and protonation of the general base are not strongly coupled in transphosphorylation and hydrolysis steps. Stronger coupling, however, is predicted for the Lys41 and His119 protonation states in apo RNase A, leading to the requirement for a microscopic kinetic model. This type of analysis may be important for other catalytic systems where the active forms of the implicated general acid and base are oppositely charged and more highly correlated. These results suggest a new way for CpHMD/pH-REMD simulations to bridge the gap with experiments to provide a molecular-level interpretation of pH-activity data in studies of enzyme mechanisms.

Interpretation of pH-activity Profiles for Acid-Base Catalysis from Molecular Simulations

PubMed Central

Dissanayake, Thakshila; Swails, Jason; Harris, Michael E.; Roitberg, Adrian E.; York, Darrin M.

2015-01-01

The measurement of reaction rate as a function of pH provides essential information about mechanism. These rates are sensitive to the pKa values of amino acids directly involved in catalysis that are often shifted by the enzyme active site environment. Experimentally observed pH-rate profiles are usually interpreted using simple kinetic models that allow estimation of “apparent pKa” values of presumed general acid and base catalysts. One of the underlying assumptions in these models is that the protonation states are uncorrelated. In the present work, we introduce the use of constant pH molecular dynamics simulations in explicit solvent (CpHMD) with replica exchange in the pH-dimension (pH-REMD) as a tool to aid in the interpretation of pH-activity data of enzymes, and test the validity of different kinetic models. We apply the methods to RNase A, a prototype acid/base catalyst, to predict the macroscopic and microscopic pKa values, as well as the shape of the pH-rate profile. Results for apo and cCMP-bound RNase A agree well with available experimental data, and suggest that deprotonation of the general acid and protonation of the general base are not strongly coupled in transphosphorylation and hydrolysis steps. Stronger coupling, however, is predicted for the Lys41 and His119 protonation states in apo RNase A, leading to the requirement for a microscopic kinetic model. This type of analysis may be important for other catalytic systems where the active forms of implicated general acid and base are oppositely charged and more highly correlated. These results suggest a new way for CpHMD/pH-REMD simulations to bridge the gap with experiments to provide a molecular-level interpretation of pH-activity data in studies of enzyme mechanisms. PMID:25615525

Raman investigation with group theoretical method on structural polymorphism of the nonlinear optical hexamine: p-nitrophenol cocrystals

NASA Astrophysics Data System (ADS)

Vijayalakshmi, S.; Kalyanaraman, S.; Ravindran, T. R.

2014-09-01

We have synthesized organic non-centrosymmetric cocrystals of 1:1 and 1:2 mole ratios of non-proton-transferred hexamine and p-nitrophenol complexes by using a slow evaporation method. The cocrystal with different stoichiometric variation gets crystallized into different crystallographic structures. The non-proton-transfer process of the complexes and the charge transfer (CT) interaction are established through Fourier transform infrared (FTIR) spectroscopy. The contribution of the water molecule in the 1:2 adduct is explained through FTIR analysis. The result has an important bearing in our present study. Existence of two different crystallographic structures (polymorphism) is confirmed by the lower frequency modes that appeared in Raman spectra. The variation in the Raman active modes at lower frequencies that arise on account of polymorphism is addressed through factor group analysis. From the UV-vis analysis, the interesting result of hyperchromic and hypochromic shifts being observed in the 1:1 and 1:2 adducts, respectively, supports the polymorphic behavior. On seeing the variation in properties, particularly nonlinear optical properties, the higher second harmonic generation (SHG) efficiency compared with KDP is observed by using the Kurtz-Perry method for both complexes.

Detailed Analysis of the Binding Mode of Vanilloids to Transient Receptor Potential Vanilloid Type I (TRPV1) by a Mutational and Computational Study

PubMed Central

Mori, Yoshikazu; Ogawa, Kazuo; Warabi, Eiji; Yamamoto, Masahiro; Hirokawa, Takatsugu

2016-01-01

Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel and a multimodal sensor protein. Since the precise structure of TRPV1 was obtained by electron cryo-microscopy, the binding mode of representative agonists such as capsaicin and resiniferatoxin (RTX) has been extensively characterized; however, detailed information on the binding mode of other vanilloids remains lacking. In this study, mutational analysis of human TRPV1 was performed, and four agonists (capsaicin, RTX, [6]-shogaol and [6]-gingerol) were used to identify amino acid residues involved in ligand binding and/or modulation of proton sensitivity. The detailed binding mode of each ligand was then simulated by computational analysis. As a result, three amino acids (L518, F591 and L670) were newly identified as being involved in ligand binding and/or modulation of proton sensitivity. In addition, in silico docking simulation and a subsequent mutational study suggested that [6]-gingerol might bind to and activate TRPV1 in a unique manner. These results provide novel insights into the binding mode of various vanilloids to the channel and will be helpful in developing a TRPV1 modulator. PMID:27606946

Catalytic Activity of Thiolate-Bridged Diruthenium Complexes Bearing Pendent Ether Moieties in the Oxidation of Molecular Dihydrogen.

PubMed

Yuki, Masahiro; Sakata, Ken; Kikuchi, Shoma; Kawai, Hiroyuki; Takahashi, Tsuyoshi; Ando, Masaki; Nakajima, Kazunari; Nishibayashi, Yoshiaki

2017-01-23

Thiolate-bridged diruthenium complexes bearing pendent ethers have been found to work as effective catalysts toward the oxidation of molecular dihydrogen into protons and electrons in water. The pendent ether moiety in the complex plays an important role to facilitate the proton transfer between the metal center and the external proton acceptor. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Measuring Interference of Drug-Like Molecules with the Respiratory Chain: Toward the Early Identification of Mitochondrial Uncouplers in Lead Finding

PubMed Central

Matter, Hans; Diekert, Kerstin; Dörner, Wolfgang; Dröse, Stefan; Licher, Thomas

2013-01-01

Abstract The electron transport chain (ETC) couples electron transfer between donors and acceptors with proton transport across the inner mitochondrial membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate (ATP). Proton transfer is based on the activity of complex I–V proteins in the ETC. The overall electrical activity of these proteins can be measured by proton transfer using Solid Supported Membrane technology. We tested the activity of complexes I, III, and V in a combined assay, called oxidative phosphorylation assay (oxphos assay), by activating each complex with the corresponding substrate. The oxphos assay was used to test in-house substances from different projects and several drugs currently available on the market that have reported effects on mitochondrial functions. The resulting data were compared to the influence of the respective compounds on mitochondria as determined by oxygen consumption and to data generated with an ATP depletion assay. The comparison shows that the oxidative phosphorylation assay provides both a rapid approach for detecting interaction of compounds with respiratory chain proteins and information on their mode of interaction. Therefore, the oxphos assay is a useful tool to support structure activity relationship studies by allowing early identification of mitotoxicity and for analyzing the outcome of phenotypic screens that are susceptible to the generation of mitotoxicity-related artifacts. PMID:23992120

Ground-state proton decay of 69Br and implications for the rp -process 68Se waiting-point

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

Rogers, Andrew M; Shapira, Dan; Lynch, William

2011-01-01

The first direct measurement of the proton separation energy, S p , for the proton-unbound nucleus 69Br is reported. Of interest is the exponential dependence of the 2 p-capture rate on S p which can bypass the 68Se waiting-point in the astrophysical rp process. An analysis of the observed proton decay spectrum is given in terms of the 69Se mirror nucleus and the influence of S p is explored within the context of a single-zone X-ray burst model.

The General Base in the Thymidylate Synthase Catalyzed Proton Abstraction

PubMed Central

Ghosh, Ananda K.; Islam, Zahidul; Krueger, Jonathan; Abeysinghe, Don Thelma; Kohen, Amnon

2015-01-01

The enzyme thymidylate synthase (TSase), an important chemotherapeutic drug target, catalyzes the formation of 2′-deoxythymidine-5′-monophosphate (dTMP), a precursor of one of the DNA building blocks. TSase catalyzes a multi-step mechanism that includes the abstraction of a proton from the C5 of the substrate 2′-deoxyuridine-5′-monophosphate (dUMP). Previous studies on ecTSase proposed that an active-site residue, Y94 serves the role of the general base abstracting this proton. However, since Y94 is neither very basic, nor connected to basic residues, nor located close enough to the pyrimidine proton to be abstracted, the actual identity of this base remains enigmatic. Based on crystal structures, an alternative hypothesis is that the nearest potential proton-acceptor of C5 of dUMP is a water molecule that is part of a hydrogen bond (H-bond) network comprised of several water molecules and several protein residues including H147, E58, N177, and Y94. Here, we examine the role of the residue Y94 in the proton abstraction step by removing its hydroxyl group (Y94F mutant). We investigated the effect of the mutation on the temperature dependence of intrinsic kinetic isotope effects (KIEs) and found that these KIEs are more temperature dependent than those of the wild-type enzyme (WT). These results suggest that the phenolic –OH of Y94 is a component of the transition state for the proton abstraction step. The findings further support the hypothesis that no single functional group is the general base, but a network of bases and hydroxyls (from water molecules and tyrosine) sharing H-bonds across the active site can serve the role of the general base to remove the pyrimidine proton. PMID:25912171

Specific activity and isotope abundances of strontium in purified strontium-82

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

Fitzsimmons, J. M.; Medvedev, D. G.; Mausner, L. F.

2015-11-12

A linear accelerator was used to irradiate a rubidium chloride target with protons to produce strontium-82 (Sr-82), and the Sr-82 was purified by ion exchange chromatography. The amount of strontium associated with the purified Sr-82 was determined by either: ICP-OES or method B which consisted of a summation of strontium quantified by gamma spectroscopy and ICP-MS. The summation method agreed within 10% to the ICP-OES for the total mass of strontium and the subsequent specific activities were determined to be 0.25–0.52 TBq mg -1. Method B was used to determine the isotope abundances by weight% of the purified Sr-82, andmore » the abundances were: Sr-82 (10–20.7%), Sr-83 (0–0.05%), Sr-84 (35–48.5%), Sr-85 (16–25%), Sr-86 (12.5–23%), Sr-87 (0%), and Sr-88 (0–10%). The purified strontium contained mass amounts of Sr-82, Sr-84, Sr-85, Sr-86, and Sr-88 in abundances not associated with natural abundance, and 90% of the strontium was produced by the proton irradiation. A comparison of ICP-OES and method B for the analysis of Sr-82 indicated analysis by ICP-OES would be easier to determine total mass of strontium and comply with regulatory requirements. An ICP-OES analytical method for Sr-82 analysis was established and validated according to regulatory guidelines.« less

A graphene-based physiometer array for the analysis of single biological cells

PubMed Central

Paulus, Geraldine L. C.; Nelson, Justin T.; Lee, Katherine Y.; Wang, Qing Hua; Reuel, Nigel F.; Grassbaugh, Brittany R.; Kruss, Sebastian; Landry, Markita P.; Kang, Jeon Woong; Vander Ende, Emma; Zhang, Jingqing; Mu, Bin; Dasari, Ramachandra R.; Opel, Cary F.; Wittrup, K. Dane; Strano, Michael S.

2014-01-01

A significant advantage of a graphene biosensor is that it inherently represents a continuum of independent and aligned sensor-units. We demonstrate a nanoscale version of a micro-physiometer – a device that measures cellular metabolic activity from the local acidification rate. Graphene functions as a matrix of independent pH sensors enabling subcellular detection of proton excretion. Raman spectroscopy shows that aqueous protons p-dope graphene – in agreement with established doping trajectories, and that graphene displays two distinct pKa values (2.9 and 14.2), corresponding to dopants physi- and chemisorbing to graphene respectively. The graphene physiometer allows micron spatial resolution and can differentiate immunoglobulin (IgG)-producing human embryonic kidney (HEK) cells from non-IgG-producing control cells. Population-based analyses allow mapping of phenotypic diversity, variances in metabolic activity, and cellular adhesion. Finally we show this platform can be extended to the detection of other analytes, e.g. dopamine. This work motivates the application of graphene as a unique biosensor for (sub)cellular interrogation. PMID:25359450

Extracellular acidification synergizes with PDGF to stimulate migration of mouse embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner

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

An, Caiyan; Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi; Clinical Medicine Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia

The elucidation of the functional mechanisms of extracellular acidification stimulating intracellular signaling pathway is of great importance for developing new targets of treatment for solid tumors, and inflammatory disorders characterized by extracellular acidification. In the present study, we focus on the regulation of extracellular acidification on intracellular signaling pathways in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at least partly involved in stimulating p38MAPK pathway through PTX-sensitive behavior to enhance cell migration in the presence or absence of platelet-derived growth factor (PDGF). Statistical analysis showed that the actions of extracellular acidic pH and PDGF on inducing enhancement ofmore » cell migration were not an additive effect. However, we also found extracellular acidic pH did inhibit the viability and proliferation of MEFs, suggesting that extracellular acidification stimulates cell migration probably through proton-sensing mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology, and real-time qPCR, we found known proton-sensing G protein-coupled receptors (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid-sensing ion channels (ASICs) were unlikely to be involved in the regulation of acidification on cell migration. In conclusion, our present study validates that extracellular acidification stimulates chemotactic migration of MEFs through activation of p38MAPK with a PTX-sensitive mechanism either by itself, or synergistically with PDGF, which was not regulated by the known proton-sensing GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or ion channels might exist in MEFs, which mediates cell migration induced by extracellular acidification in the presence or absence of PDGF. - Highlights: • Acidic pH and PDGF synergize to stimulate MEFs migration via Gi/p38MAPK pathway. • Extracellular acidification inhibits the viability and proliferation of MEFs. • MEFs sense acidic pH was not regulated by known proton-sensing GPCRs, TRPV1 or ASICs.« less

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

Collision-induced dissociation processes of protonated benzoic acid and related compounds: competitive generation of protonated carbon dioxide or protonated benzene.

PubMed

Xu, Sihang; Pavlov, Julius; Attygalle, Athula B

2017-04-01

Upon activation in the gas phase, protonated benzoic acid (m/z 123) undergoes fragmentation by several mechanisms. In addition to the predictable water loss followed by a CO loss, the m/z 123 ion more intriguingly eliminates a molecule of benzene to generate protonated carbon dioxide (H - O +  ═ C ≡ O, m/z 45), or a molecule of carbon dioxide to yield protonated benzene (m/z 79). Experimental evidence shows that the incipient proton ambulates during the fragmentation processes. For the CO 2 or benzene loss, protonated benzoic acid transfers the charge-imparting proton initially to the ortho position and then to the ipso position to generate a transient species which dissociates to form an ion-neutral complex between benzene and protonated CO 2 . The formation of the m/z 45 ion is not a phenomenon unique to benzoic acid: spectra from protonated isophthalic acid, terephthalic acid, trans-cinnamic acid and some aliphatic acids also displayed a peak for m/z 45. However, the m/z 45 peak is structurally diagnostic only for certain benzene polycarboxylic acids because the spectra of compounds with two carboxyl groups on adjacent ring carbons do not produce a peak at m/z 45. For the m/z 79 ion to be formed, an intramolecular reaction should take place in which protonated CO 2 within the ion-neutral complex acts as the attacking electrophile to transfer a proton to benzene. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Mitochondrial Proton Leak Plays a Critical Role in Pathogenesis of Cardiovascular Diseases.

PubMed

Cheng, Jiali; Nanayakkara, Gayani; Shao, Ying; Cueto, Ramon; Wang, Luqiao; Yang, William Y; Tian, Ye; Wang, Hong; Yang, Xiaofeng

2017-01-01

Mitochondrial proton leak is the principal mechanism that incompletely couples substrate oxygen to ATP generation. This chapter briefly addresses the recent progress made in understanding the role of proton leak in the pathogenesis of cardiovascular diseases. Majority of the proton conductance is mediated by uncoupling proteins (UCPs) located in the mitochondrial inner membrane. It is evident that the proton leak and reactive oxygen species (ROS) generated from electron transport chain (ETC) in mitochondria are linked to each other. Increased ROS production has been shown to induce proton conductance, and in return, increased proton conductance suppresses ROS production, suggesting the existence of a positive feedback loop that protects the biological systems from detrimental effects of augmented oxidative stress. There is mounting evidence attributing to proton leak and uncoupling proteins a crucial role in the pathogenesis of cardiovascular disease. We can surmise the role of "uncoupling" in cardiovascular disorders as follows; First, the magnitude of the proton leak and the mechanism involved in mediating the proton leak determine whether there is a protective effect against ischemia-reperfusion (IR) injury. Second, uncoupling by UCP2 preserves vascular function in diet-induced obese mice as well as in diabetes. Third, etiology determines whether the proton conductance is altered or not during hypertension. And fourth, proton leak regulates ATP synthesis-uncoupled mitochondrial ROS generation, which determines pathological activation of endothelial cells for recruitment of inflammatory cells. Continue effort in improving our understanding in the role of proton leak in the pathogenesis of cardiovascular and metabolic diseases would lead to identification of novel therapeutic targets for treatment.

Neutron yield and induced radioactivity: a study of 235-MeV proton and 3-GeV electron accelerators.

PubMed

Hsu, Yung-Cheng; Lai, Bo-Lun; Sheu, Rong-Jiun

2016-01-01

This study evaluated the magnitude of potential neutron yield and induced radioactivity of two new accelerators in Taiwan: a 235-MeV proton cyclotron for radiation therapy and a 3-GeV electron synchrotron serving as the injector for the Taiwan Photon Source. From a nuclear interaction point of view, neutron production from targets bombarded with high-energy particles is intrinsically related to the resulting target activation. Two multi-particle interaction and transport codes, FLUKA and MCNPX, were used in this study. To ensure prediction quality, much effort was devoted to the associated benchmark calculations. Comparisons of the accelerators' results for three target materials (copper, stainless steel and tissue) are presented. Although the proton-induced neutron yields were higher than those induced by electrons, the maximal neutron production rates of both accelerators were comparable according to their respective beam outputs during typical operation. Activation products in the targets of the two accelerators were unexpectedly similar because the primary reaction channels for proton- and electron-induced activation are (p,pn) and (γ,n), respectively. The resulting residual activities and remnant dose rates as a function of time were examined and discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Invited Article: Relation between electric and magnetic field structures and their proton-beam images

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

Kugland, N. L.; Ryutov, D. D.; Plechaty, C.

2012-10-15

Proton imaging is commonly used to reveal the electric and magnetic fields that are found in high energy density plasmas. Presented here is an analysis of this technique that is directed towards developing additional insight into the underlying physics. This approach considers: formation of images in the limits of weak and strong intensity variations; caustic formation and structure; image inversion to obtain line-integrated field characteristics; direct relations between images and electric or magnetic field structures in a plasma; imaging of sharp features such as Debye sheaths and shocks. Limitations on spatial and temporal resolution are assessed, and similarities with opticalmore » shadowgraphy are noted. Synthetic proton images are presented to illustrate the analysis. These results will be useful for quantitatively analyzing experimental proton imaging data and verifying numerical codes.« less

Spectroscopy of excited states of unbound nuclei 30Ar and 29Cl

NASA Astrophysics Data System (ADS)

Xu, X.-D.; Mukha, I.; Grigorenko, L. V.; Scheidenberger, C.; Acosta, L.; Casarejos, E.; Chudoba, V.; Ciemny, A. A.; Dominik, W.; Duénas-Díaz, J.; Dunin, V.; Espino, J. M.; Estradé, A.; Farinon, F.; Fomichev, A.; Geissel, H.; Golubkova, T. A.; Gorshkov, A.; Janas, Z.; Kamiński, G.; Kiselev, O.; Knöbel, R.; Krupko, S.; Kuich, M.; Litvinov, Yu. A.; Marquinez-Durán, G.; Martel, I.; Mazzocchi, C.; Nociforo, C.; Ordúz, A. K.; Pfützner, M.; Pietri, S.; Pomorski, M.; Prochazka, A.; Rymzhanova, S.; Sánchez-Benítez, A. M.; Sharov, P.; Simon, H.; Sitar, B.; Slepnev, R.; Stanoiu, M.; Strmen, P.; Szarka, I.; Takechi, M.; Tanaka, Y. K.; Weick, H.; Winkler, M.; Winfield, J. S.

2018-03-01

Several states of proton-unbound isotopes 30Ar and 29Cl were investigated by measuring their in-flight decay products, 28S + proton + proton and 28S + proton, respectively. A refined analysis of 28S-proton angular correlations indicates that the ground state of 30Ar is located at 2 .45-0.10+0.05 MeV above the two-proton emission threshold. The investigation of the decay mechanism of the 30Ar ground state demonstrates that it has the transition dynamics. In the "transitional" region, the correlation patterns of the decay products present a surprisingly strong sensitivity to the two-proton decay energy of the 30Ar ground state and the one-proton decay energy as well as the one-proton decay width of the 29Cl ground state. The comparison of the experimental 28S-proton angular correlations with those resulting from Monte Carlo simulations of the detector response illustrates that other observed 30Ar excited states decay by sequential emission of protons via intermediate resonances in 29Cl. Based on the findings, the decay schemes of the observed states in 30Ar and 29Cl were constructed. For calibration purposes and for checking the performance of the experimental setup, decays of the previously known states of a two-proton emitter 19Mg were remeasured. Evidences for one new excited state in 19Mg and two unknown states in 18Na were found.

Minimizing treatment planning errors in proton therapy using failure mode and effects analysis

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

Zheng, Yuanshui, E-mail: yuanshui.zheng@okc.procure.com; Johnson, Randall; Larson, Gary

Purpose: Failure mode and effects analysis (FMEA) is a widely used tool to evaluate safety or reliability in conventional photon radiation therapy. However, reports about FMEA application in proton therapy are scarce. The purpose of this study is to apply FMEA in safety improvement of proton treatment planning at their center. Methods: The authors performed an FMEA analysis of their proton therapy treatment planning process using uniform scanning proton beams. The authors identified possible failure modes in various planning processes, including image fusion, contouring, beam arrangement, dose calculation, plan export, documents, billing, and so on. For each error, the authorsmore » estimated the frequency of occurrence, the likelihood of being undetected, and the severity of the error if it went undetected and calculated the risk priority number (RPN). The FMEA results were used to design their quality management program. In addition, the authors created a database to track the identified dosimetric errors. Periodically, the authors reevaluated the risk of errors by reviewing the internal error database and improved their quality assurance program as needed. Results: In total, the authors identified over 36 possible treatment planning related failure modes and estimated the associated occurrence, detectability, and severity to calculate the overall risk priority number. Based on the FMEA, the authors implemented various safety improvement procedures into their practice, such as education, peer review, and automatic check tools. The ongoing error tracking database provided realistic data on the frequency of occurrence with which to reevaluate the RPNs for various failure modes. Conclusions: The FMEA technique provides a systematic method for identifying and evaluating potential errors in proton treatment planning before they result in an error in patient dose delivery. The application of FMEA framework and the implementation of an ongoing error tracking system at their clinic have proven to be useful in error reduction in proton treatment planning, thus improving the effectiveness and safety of proton therapy.« less

Minimizing treatment planning errors in proton therapy using failure mode and effects analysis.

PubMed

Zheng, Yuanshui; Johnson, Randall; Larson, Gary

2016-06-01

Failure mode and effects analysis (FMEA) is a widely used tool to evaluate safety or reliability in conventional photon radiation therapy. However, reports about FMEA application in proton therapy are scarce. The purpose of this study is to apply FMEA in safety improvement of proton treatment planning at their center. The authors performed an FMEA analysis of their proton therapy treatment planning process using uniform scanning proton beams. The authors identified possible failure modes in various planning processes, including image fusion, contouring, beam arrangement, dose calculation, plan export, documents, billing, and so on. For each error, the authors estimated the frequency of occurrence, the likelihood of being undetected, and the severity of the error if it went undetected and calculated the risk priority number (RPN). The FMEA results were used to design their quality management program. In addition, the authors created a database to track the identified dosimetric errors. Periodically, the authors reevaluated the risk of errors by reviewing the internal error database and improved their quality assurance program as needed. In total, the authors identified over 36 possible treatment planning related failure modes and estimated the associated occurrence, detectability, and severity to calculate the overall risk priority number. Based on the FMEA, the authors implemented various safety improvement procedures into their practice, such as education, peer review, and automatic check tools. The ongoing error tracking database provided realistic data on the frequency of occurrence with which to reevaluate the RPNs for various failure modes. The FMEA technique provides a systematic method for identifying and evaluating potential errors in proton treatment planning before they result in an error in patient dose delivery. The application of FMEA framework and the implementation of an ongoing error tracking system at their clinic have proven to be useful in error reduction in proton treatment planning, thus improving the effectiveness and safety of proton therapy.

Determination of solar proton fluxes and energies at high solar latitudes by UV radiation measurements

NASA Technical Reports Server (NTRS)

Witt, N.; Blum, P. W.; Ajello, J. M.

1981-01-01

The latitudinal variation of the solar proton flux and energy causes a density increase at high solar latitudes of the neutral gas penetrating the heliosphere. Measurements of the neutral density by UV resonance radiation observations from interplanetary spacecraft thus permit deductions on the dependence of the solar proton flux on heliographic latitude. Using both the results of Mariner 10 measurements and of other off-ecliptic solar wind observations, the values of the solar proton fluxes and energies at polar heliographic latitudes are determined for several cases of interest. The Mariner 10 analysis, together with IPS results, indicate a significant decrease of the solar proton flux at polar latitudes.

Proton Effects and Test Issues for Satellite Designers

NASA Technical Reports Server (NTRS)

Marshall, Cheryl J.; Marshall, Paul W.

1999-01-01

Microelectronic and photonic systems in the natural space environment are bombarded by a variety of charged particles including electrons, trapped protons, cosmic rays, and solar particles (protons and other heavy ions). These incident particles cause both ionizing and non-ionizing effects when traversing a device, and the effects can be either transient or permanent. The vast majority of the kinetic energy of an incident proton is lost to ionization, creating the single event effects (SEES) and total ionizing dose (TID) effects. However, the small portion of energy lost in non-ionizing processes causes atoms to be removed from their lattice sites and form permanent electrically active defects in semiconductor materials. These defects, i.e., "displacement damage," can significantly degrade device performance. In general, most of the displacement damage effects in the natural space environment can be attributed to protons since they are plentiful and extremely energetic (and therefore not readily shielded against). For this reason, we consider only proton induced displacement damage in this course. (Nevertheless, we identify solar cells as an important example of a case where both electron and proton damage can be important since only very light shielding is feasible.) The interested reader is encouraged to explore the three previous NSREC and RADECS short courses which also treat displacement damage issues for satellite applications. Part A of this segment of the short course introduces the space environment, proton shielding issues, and requirements specifications for proton-rich environments. In order to exercise the displacement damage analysis tools for on-orbit performance predictions, the requirements document must provide the relevant proton spectra in addition to the usual total ionizing dose-depth curves. Ion-solid interactions and the nature of the displacement damage they generate have been studied extensively for over half a century, yet they still remain a subject of investigation. In this section, a description of the mechanisms by which displacement damage is produced will be followed by a summary of the major consequences for device performance in a space environment. Often the degradation of a device parameter can be characterized by a damage factor (measured in a laboratory using monoenergetic protons) that is simply the change in a particular electrical or optical parameter per unit proton fluence. In addition, we will describe the concept of a non-ionizing energy loss rate (NIEL) which quantifies that portion of the energy lost by an incident ion that goes into displacements. It has been calculated as a function of proton energy, and is analogous to (and has the same units as) the linear energy transfer (LET) for ionizing energy. We will discover that, to first order, the calculated NIEL describes the energy dependence of the measured device damage factors. This observation provides the basis for predicting proton induced device degradation in a space environment based on both the calculated NIEL and relatively few laboratory test measurements. The methodology of such on-orbit device performance predictions will be described, as well as the limitations. Several classes of devices for which displacement damage is a significant (if not the dominant) mode of radiation induced degradation will be presented.

Thermodynamic analysis of Bacillus subtilis endospore protonation using isothermal titration calorimetry

NASA Astrophysics Data System (ADS)

Harrold, Zoë R.; Gorman-Lewis, Drew

2013-05-01

Bacterial proton and metal adsorption reactions have the capacity to affect metal speciation and transport in aqueous environments. We coupled potentiometric titration and isothermal titration calorimetry (ITC) analyses to study Bacillus subtilis spore-proton adsorption. We modeled the potentiometric data using a four and five-site non-electrostatic surface complexation model (NE-SCM). Heats of spore surface protonation from coupled ITC analyses were used to determine site specific enthalpies of protonation based on NE-SCMs. The five-site model resulted in a substantially better model fit for the heats of protonation but did not significantly improve the potentiometric titration model fit. The improvement observed in the five-site protonation heat model suggests the presence of a highly exothermic protonation reaction circa pH 7 that cannot be resolved in the less sensitive potentiometric data. From the log Ks and enthalpies we calculated corresponding site specific entropies. Log Ks and site concentrations describing spore surface protonation are statistically equivalent to B. subtilis cell surface protonation constants. Spore surface protonation enthalpies, however, are more exothermic relative to cell based adsorption suggesting a different bonding environment. The thermodynamic parameters defined in this study provide insight on molecular scale spore-surface protonation reactions. Coupled ITC and potentiometric titrations can reveal highly exothermic, and possibly endothermic, adsorption reactions that are overshadowed in potentiometric models alone. Spore-proton adsorption NE-SCMs derived in this study provide a framework for future metal adsorption studies.

Binding Site Configurations Probe the Structure and Dynamics of the Zinc Finger of NEMO (NF-κB Essential Modulator).

PubMed

Godwin, Ryan C; Melvin, Ryan L; Gmeiner, William H; Salsbury, Freddie R

2017-01-31

Zinc-finger proteins are regulators of critical signaling pathways for various cellular functions, including apoptosis and oncogenesis. Here, we investigate how binding site protonation states and zinc coordination influence protein structure, dynamics, and ultimately function, as these pivotal regulatory proteins are increasingly important for protein engineering and therapeutic discovery. To better understand the thermodynamics and dynamics of the zinc finger of NEMO (NF-κB essential modulator), as well as the role of zinc, we present results of 20 μs molecular dynamics trajectories, 5 μs for each of four active site configurations. Consistent with experimental evidence, the zinc ion is essential for mechanical stabilization of the functional, folded conformation. Hydrogen bond motifs are unique for deprotonated configurations yet overlap in protonated cases. Correlated motions and principal component analysis corroborate the similarity of the protonated configurations and highlight unique relationships of the zinc-bound configuration. We hypothesize a potential mechanism for zinc binding from results of the thiol configurations. The deprotonated, zinc-bound configuration alone predominantly maintains its tertiary structure throughout all 5 μs and alludes rare conformations potentially important for (im)proper zinc-finger-related protein-protein or protein-DNA interactions.

Characterizing proton-activated materials to develop PET-mediated proton range verification markers

NASA Astrophysics Data System (ADS)

Cho, Jongmin; Ibbott, Geoffrey S.; Kerr, Matthew D.; Amos, Richard A.; Stingo, Francesco C.; Marom, Edith M.; Truong, Mylene T.; Palacio, Diana M.; Betancourt, Sonia L.; Erasmus, Jeremy J.; DeGroot, Patricia M.; Carter, Brett W.; Gladish, Gregory W.; Sabloff, Bradley S.; Benveniste, Marcelo F.; Godoy, Myrna C.; Patil, Shekhar; Sorensen, James; Mawlawi, Osama R.

2016-06-01

Conventional proton beam range verification using positron emission tomography (PET) relies on tissue activation alone and therefore requires particle therapy PET whose installation can represent a large financial burden for many centers. Previously, we showed the feasibility of developing patient implantable markers using high proton cross-section materials (18O, Cu, and 68Zn) for in vivo proton range verification using conventional PET scanners. In this technical note, we characterize those materials to test their usability in more clinically relevant conditions. Two phantoms made of low-density balsa wood (~0.1 g cm-3) and beef (~1.0 g cm-3) were embedded with Cu or 68Zn foils of several volumes (10-50 mm3). The metal foils were positioned at several depths in the dose fall-off region, which had been determined from our previous study. The phantoms were then irradiated with different proton doses (1-5 Gy). After irradiation, the phantoms with the embedded foils were moved to a diagnostic PET scanner and imaged. The acquired data were reconstructed with 20-40 min of scan time using various delay times (30-150 min) to determine the maximum contrast-to-noise ratio. The resultant PET/computed tomography (CT) fusion images of the activated foils were then examined and the foils’ PET signal strength/visibility was scored on a 5 point scale by 13 radiologists experienced in nuclear medicine. For both phantoms, the visibility of activated foils increased in proportion to the foil volume, dose, and PET scan time. A linear model was constructed with visibility scores as the response variable and all other factors (marker material, phantom material, dose, and PET scan time) as covariates. Using the linear model, volumes of foils that provided adequate visibility (score 3) were determined for each dose and PET scan time. The foil volumes that were determined will be used as a guideline in developing practical implantable markers.

Mesure des champs de radiation dans le detecteur ATLAS et sa caverne avec les detecteurs au silicium a pixels ATLAS-MPX

NASA Astrophysics Data System (ADS)

Bouchami, Jihene

The LHC proton-proton collisions create a hard radiation environment in the ATLAS detector. In order to quantify the effects of this environment on the detector performance and human safety, several Monte Carlo simulations have been performed. However, direct measurement is indispensable to monitor radiation levels in ATLAS and also to verify the simulation predictions. For this purpose, sixteen ATLAS-MPX devices have been installed at various positions in the ATLAS experimental and technical areas. They are composed of a pixelated silicon detector called MPX whose active surface is partially covered with converter layers for the detection of thermal, slow and fast neutrons. The ATLAS-MPX devices perform real-time measurement of radiation fields by recording the detected particle tracks as raster images. The analysis of the acquired images allows the identification of the detected particle types by the shapes of their tracks. For this aim, a pattern recognition software called MAFalda has been conceived. Since the tracks of strongly ionizing particles are influenced by charge sharing between adjacent pixels, a semi-empirical model describing this effect has been developed. Using this model, the energy of strongly ionizing particles can be estimated from the size of their tracks. The converter layers covering each ATLAS-MPX device form six different regions. The efficiency of each region to detect thermal, slow and fast neutrons has been determined by calibration measurements with known sources. The study of the ATLAS-MPX devices response to the radiation produced by proton-proton collisions at a center of mass energy of 7 TeV has demonstrated that the number of recorded tracks is proportional to the LHC luminosity. This result allows the ATLAS-MPX devices to be employed as luminosity monitors. To perform an absolute luminosity measurement and calibration with these devices, the van der Meer method based on the LHC beam parameters has been proposed. Since the ATLAS-MPX devices response and the luminosity are correlated, the results of measuring radiation levels are expressed in terms of particle fluences per unit integrated luminosity. A significant deviation has been obtained when comparing these fluences with those predicted by GCALOR, which is one of the ATLAS detector simulations. In addition, radiation measurements performed at the end of proton-proton collisions have demonstrated that the decay of radionuclides produced during collisions can be observed with the ATLAS-MPX devices. The residual activation of ATLAS components can be measured with these devices by means of ambient dose equivalent calibration. Keywords: pattern recognition, charge sharing effect, neutron detection efficiency, luminosity, van der Meer method, particle fluences, GCALOR simulation, residual activation, ambient dose equivalent.

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

Mechanistic Insight from Calorimetric Measurements of the Assembly of the Binuclear Metal Active Site of Glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes.

PubMed

Pedroso, Marcelo M; Ely, Fernanda; Carpenter, Margaret C; Mitić, Nataša; Gahan, Lawrence R; Ollis, David L; Wilcox, Dean E; Schenk, Gerhard

2017-07-05

Glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes is a binuclear metallohydrolase with a high affinity for metal ions at its α site but a lower affinity at its β site in the absence of a substrate. Isothermal titration calorimetry (ITC) has been used to quantify the Co(II) and Mn(II) binding affinities and thermodynamics of the two sites in wild-type GpdQ and two mutants, both in the absence and in the presence of phosphate. Metal ions bind to the six-coordinate α site in an entropically driven process with loss of a proton, while binding at the β site is not detected by ITC. Phosphate enhances the metal affinity of the α site by increasing the binding entropy and the metal affinity of the β site by enthalpic (Co) or entropic (Mn) contributions, but no additional loss of protons. Mutations of first- and second-coordination sphere residues at the β site increase the metal affinity of both sites by enhancing the binding enthalpy. In particular, loss of the hydrogen bond from second-sphere Ser127 to the metal-coordinating Asn80 has a significant effect on the metal binding thermodynamics that result in a resting binuclear active site with high catalytic activity. While structural and spectroscopic data with excess metal ions have indicated a bridging hydroxide in the binuclear GpdQ site, analysis of ITC data here reveals the loss of a single proton in the assembly of this site, indicating that the metal-bound hydroxide nucleophile is formed in the resting inactive mononuclear form, which becomes catalytically competent upon binding the second metal ion.

Application of activation methods on the Dubna experimental transmutation set-ups.

PubMed

Stoulos, S; Fragopoulou, M; Adloff, J C; Debeauvais, M; Brandt, R; Westmeier, W; Krivopustov, M; Sosnin, A; Papastefanou, C; Zamani, M; Manolopoulou, M

2003-02-01

High spallation neutron fluxes were produced by irradiating massive heavy targets with proton beams in the GeV range. The experiments were performed at the Dubna High Energy Laboratory using the nuclotron accelerator. Two different experimental set-ups were used to produce neutron spectra convenient for transmutation of radioactive waste by (n,x) reactions. By a theoretical analysis neutron spectra can be reproduced from activation measurements. Thermal-epithermal and fast-super-fast neutron fluxes were estimated using the 197Au, 238U (n,gamma) and (n,2n) reactions, respectively. Depleted uranium transmutation rates were also studied in both experiments.

Proton-Induced Conductivity Enhancement in AlGaN/GaN HEMT Devices

NASA Astrophysics Data System (ADS)

Lee, In Hak; Lee, Chul; Choi, Byoung Ki; Yun, Yeseul; Chang, Young Jun; Jang, Seung Yup

2018-04-01

We investigated the influence of proton irradiation on the AlGaN/GaN high-electron-mobility transistor (HEMT) devices. Unlike previous studies on the degradation behavior upon proton irradiation, we observed improvements in their electrical conductivity and carrier concentration of up to 25% for the optimal condition. As we increased the proton dose, the carrier concentration and the mobility showed a gradual increase and decrease, respectively. From the photoluminescence measurements, we observed a reduction in the near-band-edge peak of GaN ( 366 nm), which correlate on the observed electrical properties. However, neither the Raman nor the X-ray diffraction analysis showed any changes, implying a negligible influence of protons on the crystal structures. We demonstrated that high-energy proton irradiation could be utilized to modify the transport properties of HEMT devices without damaging their crystal structures.

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

Smith, R.E.

This report describes the analysis of carbonxyl-terminated butadiene (CTB), carboxyl-terminated butadiene/acrylonitrile (CTBN), and a CTBN adduct prepared by reaction with Epon 828. Data from gel permeation chromatography, nuclear magnetic resonance spectroscopy, high performance liquid chromatography, and ion chromatography are presented and discussed. Quantitative methods based on carbon-13 and proton NMR for analyzing CTBN are described. Proton NMR was found to be useful in identifying lots that have an abnormal amount of CTBN protons. One such lot exhibited a phase separation of a polybutadiene impurity. Carbon-13 NMR was found to be capable of determining nitrile content directly. Carbon-13 NMR had amore » relative standard deviation of 8.3% and a proton NMR of 3.9%. Proton NMR was found to be useful in identifying lots that have 5% more CTBN protons than other lots. 3 refs., 11 figs., 4 tabs.« less

Analysis of Dark Current in BRITE Nanostellite CCD Sensors †

PubMed Central

Popowicz, Adam

2018-01-01

The BRightest Target Explorer (BRITE) is the pioneering nanosatellite mission dedicated for photometric observations of the brightest stars in the sky. The BRITE charge coupled device (CCD) sensors are poorly shielded against extensive flux of energetic particles which constantly induce defects in the silicon lattice. In this paper we investigate the temporal evolution of the generation of the dark current in the BRITE CCDs over almost four years after launch. Utilizing several steps of image processing and employing normalization of the results, it was possible to obtain useful information about the progress of thermal activity in the sensors. The outcomes show a clear and consistent linear increase of induced damage despite the fact that only about 0.14% of CCD pixels were probed. By performing the analysis of temperature dependencies of the dark current, we identified the observed defects as phosphorus-vacancy (PV) pairs, which are common in proton irradiated CCD matrices. Moreover, the Meyer-Neldel empirical rule was confirmed in our dark current data, yielding EMN=24.8 meV for proton-induced PV defects. PMID:29415471

Proton decay and light sterile neutrinos

NASA Astrophysics Data System (ADS)

Helo, Juan C.; Hirsch, Martin; Ota, Toshihiko

2018-06-01

Within the standard model, non-renormalizable operators at dimension six ( d = 6) violate baryon and lepton number by one unit and thus lead to proton decay. Here, we point out that the proton decay mode with a charged pion and missing energy can be a characteristic signature of d = 6 operators containing a light sterile neutrino, if it is not accompanied by the standard π0 e + final state. We discuss this effect first at the level of effective operators and then provide a concrete model with new physics at the TeV scale, in which the lightness of the active neutrinos and the stability of the proton are related.

Solar-cosmic-ray fluxes during the last ten million years

NASA Technical Reports Server (NTRS)

Reedy, Robert C.; Marti, Kurt

1991-01-01

The fluxes of energetic (E is greater than or approximately equal to 10 MeV) solar particles in the vicinity of the earth in the past can be determined from nuclides that they produced in the top centimeter of lunar rocks. Activity-vs-depth profiles of short-lived radioactivities measured in the top centimeter of lunar rocks agree with profiles calculated with directly measured solar-proton fluxes since about 1965 and were used with indirect observations to get solar-proton fluxes back to 1956. Lunar-rock profiles for long-lived radionuclides have been used to infer solar-proton fluxes averaged over several time periods in the past. New results are reported for solar-proton-produced Kr-81 measured in lunar rock 68815. Activities of 76,000-yr Ni-59 can be used to get fluxes of solar alpha particles averaged over the last 100,000 yr. The average solar-proton fluxes in the past are not greatly different from those observed during the last three 11-yr solar cycles. The work that needs to be done to determine more and better fluxes of energetic particles from the sun in the past is discussed.

Modelling PET radionuclide production in tissue and external targets using Geant4

NASA Astrophysics Data System (ADS)

Amin, T.; Infantino, A.; Lindsay, C.; Barlow, R.; Hoehr, C.

2017-07-01

The Proton Therapy Facility in TRIUMF provides 74 MeV protons extracted from a 500 MeV H- cyclotron for ocular melanoma treatments. During treatment, positron emitting radionuclides such as 1C, 15O and 13N are produced in patient tissue. Using PET scanners, the isotopic activity distribution can be measured for in-vivo range verification. A second cyclotron, the TR13, provides 13 MeV protons onto liquid targets for the production of PET radionuclides such as 18F, 13N or 68Ga, for medical applications. The aim of this work was to validate Geant4 against FLUKA and experimental measurements for production of the above-mentioned isotopes using the two cyclotrons. The results show variable degrees of agreement. For proton therapy, the proton-range agreement was within 2 mm for 11C activity, whereas 13N disagreed. For liquid targets at the TR13 the average absolute deviation ratio between FLUKA and experiment was 1.9±2.7, whereas the average absolute deviation ratio between Geant4 and experiment was 0. 6±0.4. This is due to the uncertainties present in experimentally determined reaction cross sections.

Uncoupling protein and ATP/ADP carrier increase mitochondrial proton conductance after cold adaptation of king penguins.

PubMed

Talbot, Darren A; Duchamp, Claude; Rey, Benjamin; Hanuise, Nicolas; Rouanet, Jean Louis; Sibille, Brigitte; Brand, Martin D

2004-07-01

Juvenile king penguins develop adaptive thermogenesis after repeated immersion in cold water. However, the mechanisms of such metabolic adaptation in birds are unknown, as they lack brown adipose tissue and uncoupling protein-1 (UCP1), which mediate adaptive non-shivering thermogenesis in mammals. We used three different groups of juvenile king penguins to investigate the mitochondrial basis of avian adaptive thermogenesis in vitro. Skeletal muscle mitochondria isolated from penguins that had never been immersed in cold water showed no superoxide-stimulated proton conductance, indicating no functional avian UCP. Skeletal muscle mitochondria from penguins that had been either experimentally immersed or naturally adapted to cold water did possess functional avian UCP, demonstrated by a superoxide-stimulated, GDP-inhibitable proton conductance across their inner membrane. This was associated with a markedly greater abundance of avian UCP mRNA. In the presence (but not the absence) of fatty acids, these mitochondria also showed a greater adenine nucleotide translocase-catalysed proton conductance than those from never-immersed penguins. This was due to an increase in the amount of adenine nucleotide translocase. Therefore, adaptive thermogenesis in juvenile king penguins is linked to two separate mechanisms of uncoupling of oxidative phosphorylation in skeletal muscle mitochondria: increased proton transport activity of avian UCP (dependent on superoxide and inhibited by GDP) and increased proton transport activity of the adenine nucleotide translocase (dependent on fatty acids and inhibited by carboxyatractylate).

ULF waves associated with enhanced subauroral proton precipitation

NASA Astrophysics Data System (ADS)

Immel, Thomas J.; Mende, S. B.; Frey, H. U.; Patel, J.; Bonnell, J. W.; Engebretson, M. J.; Fuselier, S. A.

Several types of sub-auroral proton precipitation events have been identified using the Spectrographic Imager (SI) onboard the NASA-IMAGE satellite, including dayside subauroral proton flashes and detached proton arcs in the dusk sector. These have been observed at various levels of geomagnetic activity and solar wind conditions and the mechanism driving the precipitation has often been assumed to be scattering of protons into the loss cone by enhancement of ion-cyclotron waves in the interaction of the thermal plasmaspheric populations and more energetic ring current particles. Indeed, recent investigation of the detached arcs using the MPA instruments aboard the LANL geosynchronous satellites has shown there are nearly always heightened densities of cold plasma on high-altitude field lines which map down directly to the sub-auroral precipitation. If the ion-cyclotron instability is a causative mechanism, the enhancement of wave activity at ion-cyclotron frequencies should be measurable. It is here reported that magnetic pulsations in the Pc1 range occur in the vicinity of each of 4 detached arcs observed in 2000-2002, though with widely varying signatures. Additionally, longer period pulsations in the Pc5 ranges are also observed in the vicinity of the arcs, leading to the conclusion that a bounce-resonance of ring-current protons with the azimuthal Pc5 wave structure may also contribute to the detached precipitation.

The kinetics of the decompositions of the proton bound dimers of 1,4-dimethylpyridine and dimethyl methylphosphonate from atmospheric pressure ion mobility spectra

NASA Astrophysics Data System (ADS)

Ewing, R. G.; Eiceman, G. A.; Harden, C. S.; Stone, J. A.

2006-09-01

The rate constants for the dissociations, A2H+ --> AH+ + A, of the symmetrical proton bound dimers of 2,4-dimethylpyridine and dimethyl methylphosphonate have been determined using an ion mobility spectrometer operating with air as drift gas at ambient pressure. Reaction time was varied by varying the drift electric field. The rate constants were derived from the mobility spectra by determining the rate at which ions decomposed in the drift region. Arrhenius plots with a drift gas containing water vapor at 5 ppmv gave the following activation energies and pre-exponential factors: 2,4-dimethylpyridine, 94 +/- 2 kJ mol-1, log A (s-1) = 15.9 +/- 0.4; dimethyl methylphosphonate, 127 +/- 3 kJ mol-1, log A (s-1) = 15.6 +/- 0.3. The enthalpy changes for the decompositions calculated from the activation energies are in accord with literature values for symmetrical proton bound dimers of oxygen and nitrogen bases. The results for dimethyl methylphosphonate were obtained over the temperature range 478-497 K and are practically independent of water concentration (5-2000 ppmv). The activation energy for 2,4-dimethylpyridine, obtained over the temperature range 340-359 K, decreased to 31 kJ mol-1 in the presence of 2.0 x 103 ppmv of water. At the low temperature, a displacement reaction involving water may account for the decrease. The reduced mobilities of the protonated molecules and the proton bound dimers have been determined over a wide temperature range. While the values for the dimers are essentially independent of the water concentration in the drift gas, those of the protonated molecules show a strong dependence.

Proton translocation coupled to trimethylamine N-oxide reduction in anaerobically grown Escherichia coli.

PubMed Central

Takagi, M; Tsuchiya, T; Ishimoto, M

1981-01-01

Proton translocation coupled to trimethylamine N-oxide reduction was studied in Escherichia coli grown anaerobically in the presence of trimethylamine N-oxide. Rapid acidification of the medium was observed when trimethylamine N-oxide was added to anaerobic cell suspensions of E. coli K-10. Acidification was sensitive to the proton conductor 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile (SF6847). No pH change was shown in a strain deficient in trimethylamine N-oxide reductase activity. The apparent H+/trimethylamine N-oxide ratio in cells oxidizing endogenous substrates was 3 to 4 g-ions of H+ translocated per mol of trimethylamine N-oxide added. The addition of trimethylamine N-oxide and formate to ethylenediaminetetraacetic acid-treated cell suspension caused fluorescence quenching of 3,3'-dipropylthiacarbocyanine [diS-C3-(5)], indicating the generation of membrane potential. These results indicate that the reduction of trimethylamine N-oxide in E. coli is catalyzed by an anaerobic electron transfer system, resulting in formation of a proton motive force. Trimethylamine N-oxide reductase activity and proton extrusion were also examined in chlorate-resistant mutants. Reduction of trimethylamine N-oxide occurred in chlC, chlG, and chlE mutants, whereas chlA, chlB, and chlD mutants, which are deficient in the molybdenum cofactor, could not reduce it. Protons were extruded in chlC and chlG mutants, but not in chlA, chlB, and chlD mutants. Trimethylamine N-oxide reductase activity in a chlD mutant was restored to the wild-type level by the addition of 100 microM molybdate to the growth medium, indicating that the same molybdenum cofactor as used by nitrate reductase is required for the trimethylamine N-oxide reductase system. PMID:7031034

SU-D-BRC-04: Development of Proton Tissue Equivalent Materials for Calibration and Dosimetry Studies

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

Olguin, E; Flampouri, S; Lipnharski, I

Purpose: To develop new proton tissue equivalent materials (PTEM), urethane and fiberglass based, for proton therapy calibration and dosimetry studies. Existing tissue equivalent plastics are applicable only for x-rays because they focus on matching mass attenuation coefficients. This study aims to create new plastics that match mass stopping powers for proton therapy applications instead. Methods: New PTEMs were constructed using urethane and fiberglass resin materials for soft, fat, bone, and lung tissue. The stoichiometric analysis method was first used to determine the elemental composition of each unknown constituent. New initial formulae were then developed for each of the 4 PTEMsmore » using the new elemental compositions and various additives. Samples of each plastic were then created and exposed to a well defined proton beam at the UF Health Proton Therapy Institute (UFHPTI) to validate its mass stopping power. Results: The stoichiometric analysis method revealed the elemental composition of the 3 components used in creating the PTEMs. These urethane and fiberglass based resins were combined with additives such as calcium carbonate, aluminum hydroxide, and phenolic micro spheres to achieve the desired mass stopping powers and densities. Validation at the UFHPTI revealed adjustments had to be made to the formulae, but the plastics eventually had the desired properties after a few iterations. The mass stopping power, density, and Hounsfield Unit of each of the 4 PTEMs were within acceptable tolerances. Conclusion: Four proton tissue equivalent plastics were developed: soft, fat, bone, and lung tissue. These plastics match each of the corresponding tissue’s mass stopping power, density, and Hounsfield Unit, meaning they are truly tissue equivalent for proton therapy applications. They can now be used to calibrate proton therapy treatment planning systems, improve range uncertainties, validate proton therapy Monte Carlo simulations, and assess in-field and out-of-field organ doses.« less

Theoretical detection limit of PIXE analysis using 20 MeV proton beams

NASA Astrophysics Data System (ADS)

Ishii, Keizo; Hitomi, Keitaro

2018-02-01

Particle-induced X-ray emission (PIXE) analysis is usually performed using proton beams with energies in the range 2∼3 MeV because at these energies, the detection limit is low. The detection limit of PIXE analysis depends on the X-ray production cross-section, the continuous background of the PIXE spectrum and the experimental parameters such as the beam currents and the solid angle and detector efficiency of X-ray detector. Though the continuous background increases as the projectile energy increases, the cross-section of the X-ray increases as well. Therefore, the detection limit of high energy proton PIXE is not expected to increase significantly. We calculated the cross sections of continuous X-rays produced in several bremsstrahlung processes and estimated the detection limit of a 20 MeV proton PIXE analysis by modelling the Compton tail of the γ-rays produced in the nuclear reactions, and the escape effect on the secondary electron bremsstrahlung. We found that the Compton tail does not affect the detection limit when a thin X-ray detector is used, but the secondary electron bremsstrahlung escape effect does have an impact. We also confirmed that the detection limit of the PIXE analysis, when used with 4 μm polyethylene backing film and an integrated beam current of 1 μC, is 0.4∼2.0 ppm for proton energies in the range 10∼30 MeV and elements with Z = 16-90. This result demonstrates the usefulness of several 10 MeV cyclotrons for performing PIXE analysis. Cyclotrons with these properties are currently installed in positron emission tomography (PET) centers.

Identification of a pre-active conformation of a pentameric channel receptor

PubMed Central

Menny, Anaïs; Lefebvre, Solène N; Schmidpeter, Philipp AM; Drège, Emmanuelle; Fourati, Zaineb; Delarue, Marc; Edelstein, Stuart J; Nimigean, Crina M; Joseph, Delphine; Corringer, Pierre-Jean

2017-01-01

Pentameric ligand-gated ion channels (pLGICs) mediate fast chemical signaling through global allosteric transitions. Despite the existence of several high-resolution structures of pLGICs, their dynamical properties remain elusive. Using the proton-gated channel GLIC, we engineered multiple fluorescent reporters, each incorporating a bimane and a tryptophan/tyrosine, whose close distance causes fluorescence quenching. We show that proton application causes a global compaction of the extracellular subunit interface, coupled to an outward motion of the M2-M3 loop near the channel gate. These movements are highly similar in lipid vesicles and detergent micelles. These reorganizations are essentially completed within 2 ms and occur without channel opening at low proton concentration, indicating that they report a pre-active intermediate state in the transition pathway toward activation. This provides a template to investigate the gating of eukaryotic neurotransmitter receptors, for which intermediate states also participate in activation. DOI: http://dx.doi.org/10.7554/eLife.23955.001 PMID:28294942

An acid-sensing ion channel from shark (Squalus acanthias) mediates transient and sustained responses to protons.

PubMed

Springauf, Andreas; Gründer, Stefan

2010-03-01

Acid-sensing ion channels (ASICs) are proton-gated Na(+) channels. They are implicated in synaptic transmission, detection of painful acidosis, and possibly sour taste. The typical ASIC current is a transient, completely desensitizing current that can be blocked by the diuretic amiloride. ASICs are present in chordates but are absent in other animals. They have been cloned from urochordates, jawless vertebrates, cartilaginous shark and bony fish, from chicken and different mammals. Strikingly, all ASICs that have so far been characterized from urochordates, jawless vertebrates and shark are not gated by protons, suggesting that proton gating evolved relatively late in bony fish and that primitive ASICs had a different and unknown gating mechanism. Recently, amino acids that are crucial for the proton gating of rat ASIC1a have been identified. These residues are completely conserved in shark ASIC1b (sASIC1b), prompting us to re-evaluate the proton sensitivity of sASIC1b. Here we show that, contrary to previous findings, sASIC1b is indeed gated by protons with half-maximal activation at pH 6.0. sASIC1b desensitizes quickly but incompletely, efficiently encoding transient as well as sustained proton signals. Our results show that the conservation of the amino acids crucial for proton gating can predict proton sensitivity of an ASIC and increase our understanding of the evolution of ASICs.

Proton-counting radiography for proton therapy: a proof of principle using CMOS APS technology

NASA Astrophysics Data System (ADS)

Poludniowski, G.; Allinson, N. M.; Anaxagoras, T.; Esposito, M.; Green, S.; Manolopoulos, S.; Nieto-Camero, J.; Parker, D. J.; Price, T.; Evans, P. M.

2014-06-01

Despite the early recognition of the potential of proton imaging to assist proton therapy (Cormack 1963 J. Appl. Phys. 34 2722), the modality is still removed from clinical practice, with various approaches in development. For proton-counting radiography applications such as computed tomography (CT), the water-equivalent-path-length that each proton has travelled through an imaged object must be inferred. Typically, scintillator-based technology has been used in various energy/range telescope designs. Here we propose a very different alternative of using radiation-hard CMOS active pixel sensor technology. The ability of such a sensor to resolve the passage of individual protons in a therapy beam has not been previously shown. Here, such capability is demonstrated using a 36 MeV cyclotron beam (University of Birmingham Cyclotron, Birmingham, UK) and a 200 MeV clinical radiotherapy beam (iThemba LABS, Cape Town, SA). The feasibility of tracking individual protons through multiple CMOS layers is also demonstrated using a two-layer stack of sensors. The chief advantages of this solution are the spatial discrimination of events intrinsic to pixelated sensors, combined with the potential provision of information on both the range and residual energy of a proton. The challenges in developing a practical system are discussed.

Proton-counting radiography for proton therapy: a proof of principle using CMOS APS technology

PubMed Central

Poludniowski, G; Allinson, N M; Anaxagoras, T; Esposito, M; Green, S; Manolopoulos, S; Nieto-Camero, J; Parker, D J; Price, T; Evans, P M

2014-01-01

Despite the early recognition of the potential of proton imaging to assist proton therapy the modality is still removed from clinical practice, with various approaches in development. For proton-counting radiography applications such as Computed Tomography (CT), the Water-Equivalent-Path-Length (WEPL) that each proton has travelled through an imaged object must be inferred. Typically, scintillator-based technology has been used in various energy/range telescope designs. Here we propose a very different alternative of using radiation-hard CMOS Active Pixel Sensor (APS) technology. The ability of such a sensor to resolve the passage of individual protons in a therapy beam has not been previously shown. Here, such capability is demonstrated using a 36 MeV cyclotron beam (University of Birmingham Cyclotron, Birmingham, UK) and a 200 MeV clinical radiotherapy beam (iThemba LABS, Cape Town, SA). The feasibility of tracking individual protons through multiple CMOS layers is also demonstrated using a two-layer stack of sensors. The chief advantages of this solution are the spatial discrimination of events intrinsic to pixelated sensors, combined with the potential provision of information on both the range and residual energy of a proton. The challenges in developing a practical system are discussed. PMID:24785680

The Ca2+-ATPase pump facilitates bidirectional proton transport across the sarco/endoplasmic reticulum.

PubMed

Espinoza-Fonseca, L Michel

2017-03-28

Ca 2+ transport across the sarco/endoplasmic reticulum (SR) plays an essential role in intracellular Ca 2+ homeostasis, signalling, cell differentiation and muscle contractility. During SR Ca 2+ uptake and release, proton fluxes are required to balance the charge deficit generated by the exchange of Ca 2+ and other ions across the SR. During Ca 2+ uptake by the SR Ca 2+ -ATPase (SERCA), two protons are countertransported from the SR lumen to the cytosol, thus partially compensating for the charge moved by Ca 2+ transport. Studies have shown that protons are also transported from the cytosol to the lumen during Ca 2+ release, but a transporter that facilitates proton transport into the SR lumen has not been described. In this article we propose that SERCA forms pores that facilitate bidirectional proton transport across the SR. We describe the location and structure of water-filled pores in SERCA that form cytosolic and luminal pathways for protons to cross the SR membrane. Based on this structural information, we suggest mechanistic models for proton translocation to the cytosol during active Ca 2+ transport, and into the SR lumen during SERCA inhibition by endogenous regulatory proteins. Finally, we discuss the physiological consequences of SERCA-mediated bidirectional proton transport across the SR membrane of muscle and non-muscle cells.

[Why proton therapy? And how?

PubMed

Thariat, Juliette; Habrand, Jean Louis; Lesueur, Paul; Chaikh, Abdulhamid; Kammerer, Emmanuel; Lecomte, Delphine; Batalla, Alain; Balosso, Jacques; Tessonnier, Thomas

2018-03-01

Proton therapy is a radiotherapy, based on the use of protons, charged subatomic particles that stop at a given depth depending on their initial energy (pristine Bragg peak), avoiding any output beam, unlike the photons used in most of the other modalities of radiotherapy. Proton therapy has been used for 60 years, but has only become ubiquitous in the last decade because of recent major advances in particle accelerator technology. This article reviews the history of clinical implementation of protons, the nature of the technological advances that now allows its expansion at a lower cost. It also addresses the technical and physical specificities of proton therapy and the clinical situations for which proton therapy may be relevant but requires evidence. Different proton therapy techniques are possible. These are explained in terms of their clinical potential by explaining the current terminology (such as cyclotrons, synchrotrons or synchrocyclotrons, using superconducting magnets, fixed line or arm rotary with passive diffusion delivery or active by scanning) in basic words. The requirements associated with proton therapy are increased due to the precision of the depth dose deposit. The learning curve of proton therapy requires that clinical indications be prioritized according to their associated uncertainties (such as range uncertainties and movement in lung tumors). Many clinical indications potentially fall under proton therapy ultimately. Clinical strategies are explained in a paralleled manuscript. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

High density scintillating glass proton imaging detector

NASA Astrophysics Data System (ADS)

Wilkinson, C. J.; Goranson, K.; Turney, A.; Xie, Q.; Tillman, I. J.; Thune, Z. L.; Dong, A.; Pritchett, D.; McInally, W.; Potter, A.; Wang, D.; Akgun, U.

2017-03-01

In recent years, proton therapy has achieved remarkable precision in delivering doses to cancerous cells while avoiding healthy tissue. However, in order to utilize this high precision treatment, greater accuracy in patient positioning is needed. An accepted approximate uncertainty of +/-3% exists in the current practice of proton therapy due to conversions between x-ray and proton stopping power. The use of protons in imaging would eliminate this source of error and lessen the radiation exposure of the patient. To this end, this study focuses on developing a novel proton-imaging detector built with high-density glass scintillator. The model described herein contains a compact homogeneous proton calorimeter composed of scintillating, high density glass as the active medium. The unique geometry of this detector allows for the measurement of both the position and residual energy of protons, eliminating the need for a separate set of position trackers in the system. Average position and energy of a pencil beam of 106 protons is used to reconstruct the image rather than by analyzing individual proton data. Simplicity and efficiency were major objectives in this model in order to present an imaging technique that is compact, cost-effective, and precise, as well as practical for a clinical setting with pencil-beam scanning proton therapy equipment. In this work, the development of novel high-density glass scintillator and the unique conceptual design of the imager are discussed; a proof-of-principle Monte Carlo simulation study is performed; preliminary two-dimensional images reconstructed from the Geant4 simulation are presented.

Evaluation of proton cross-sections for radiation sources in the proton accelerator

NASA Astrophysics Data System (ADS)

Cho, Young-Sik; Lee, Cheol-Woo; Lee, Young-Ouk

2007-08-01

Proton Engineering Frontier Project (PEFP) is currently building a proton accelerator in Korea which consists of a proton linear accelerator with 100 MeV of energy, 20 mA of current and various particle beam facilities. The final goal of this project consists of the production of 1 GeV proton beams, which will be used for various medical and industrial applications as well as for research in basic and applied sciences. Carbon and copper in the proton accelerator for PEPP, through activation, become radionuclides such as 7Be and 64Cu. Copper is a major element of the accelerator components and the carbon is planned to be used as a target material of the beam dump. A recent survey showed that the currently available cross-sections create a large difference from the experimental data in the production of some residual nuclides by the proton-induced reactions for carbon and copper. To more accurately estimate the production of radioactive nuclides in the accelerator, proton cross-sections for carbon and copper are evaluated. The TALYS code was used for the evaluation of the cross-sections for the proton-induced reactions. To obtain the cross-sections which best fits the experimental data, optical model parameters for the neutron, proton and other complex particles such as the deuteron and alpha were successively adjusted. The evaluated cross-sections in this study are compared with the measurements and other evaluations .

Density functional theory analysis of the impact of steric interaction on the function of switchable polarity solvents

DOE PAGES

McNally, Joshua S.; Noll, Bruce; Orme, Christopher J.; ...

2015-05-04

Here, a density functional theory (DFT) analysis has been performed to explore the impact of steric interactions on the function of switchable polarity solvents (SPS) and their implications on a quantitative structure-activity relationship (QSAR) model previously proposed for SPS. An x-ray crystal structure of the N,N-dimethylcyclohexylammonium bicarbonate (Hdmcha) salt has been solved as an asymmetric unit containing two cation/anion pairs, with a hydrogen bonding interaction observed between the bicarbonate anions, as well as between the cation and anion in each pair. DFT calculations provide an optimized structure of Hdmcha that closely resembles experimental data and reproduces the cation/anion interaction withmore » the inclusion of a dielectric field. Relaxed potential energy surface (PES) scans have been performed on Hdmcha-based computational model compounds, differing in the size of functional group bonded to the nitrogen center, to assess the steric impact of the group on the relative energy and structural properties of the compound. Results suggest that both the length and amount of branching associated with the substituent impact the energetic limitations on rotation of the group along the N-R bond and NC-R bond, and disrupt the energy minimized position of the hydrogen bonded bicarbonate group. The largest interaction resulted from functional groups that featured five bonds between the ammonium proton and a proton on a functional group with the freedom of rotation to form a pseudo-six membered ring which included both protons.« less

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.

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.

Modeling solubility and acid-base properties of some amino acids in aqueous NaCl and (CH3)4NCl aqueous solutions at different ionic strengths and temperatures.

PubMed

Bretti, Clemente; Giuffrè, Ottavia; Lando, Gabriele; Sammartano, Silvio

2016-01-01

New potentiometric experiments have been performed in NaCl and in (CH3)4NCl media, to determine the protonation constants, the protonation enthalpy changes and the solubility of six natural α-amino acids, namely Glycine (Gly), Alanine (Ala), Valine (Val), Leucine (Leu), Serine (Ser) and Phenylalanine (Phe). The aim of the work is the rationalization of the protonation thermodynamics (log [Formula: see text], solubility and [Formula: see text]) in NaCl, determining recommended, tentative or provisional values in selected experimental conditions and to report, for the first time, data in a weak interacting medium, as (CH3)4NCl. Literature data analysis was performed selecting the most reliable values, analyzed together with new data here reported. Significant trends and similarities were observed in the behavior of the six amino acids, and in some cases it was possible to determine common parameters for the ionic strength and temperature dependence. In general, the first protonation step, relative to the amino group, is significantly exothermic (average value is [Formula: see text] = -44.5 ± 0.4 kJ mol(-1) at infinite dilution and T = 298.15 K), and the second, relative to the carboxylate group, is fairly close to zero ([Formula: see text] = -2.5 ± 1.6, same conditions). In both cases, the main contribution to the proton binding reaction is mainly entropic in nature. For phenylalanine and leucine, solubility measurements at different concentrations of supporting electrolyte allowed to determine total and specific solubility values, then used to obtain the Setschenow and the activity coefficients of all the species involved in the protonation equilibria. The values of the first protonation constant in (CH3)4NCl are lower than the corresponding values in NaCl, due to the weak interaction between the deprotonated amino group and (CH3)4N(+). In this light, differences between the protonation functions in NaCl and (CH3)4NCl were used for the quantification of the stability of the weak [(CH3)4N(+)-L(-)] complexes that resulted log K = -0.38 ± 0.07 as an average value for the six amino acids.

Origins of Protons in C-H Bond Insertion Products of Phenols: Proton-Self-Sufficient Function via Water Molecules.

PubMed

Luo, Zhoujie; Gao, Ya; Zhu, Tong; Zhang, John Zenghui; Xia, Fei

2017-08-31

Water molecules can serve as proton shuttles for proton transfer in the C-H bond insertion reactions catalyzed by transition metal complexes. Recently, the control experiments performed for C-H bond insertion of phenol and anisol by gold carbenes show that large discrepancy exists in the yields of hydrogenated and deuterated products. Thus, we conducted a detailed theoretical analysis on the function of water molecules in the C-H bond insertion reactions. The comparison of calculated results and control experiments indicates that the solution water molecules play a crucial role of proton shuttle in C-H bond insertion. In particular, it was found that the hydroxyl groups in phenols were capable of donating protons via water shuttles for the production of C-H products, which had a substantial influence on the yields of inserted products. The hydroxyl groups instead of C-H bonds in phenols function like "proton reservoirs" in the C-H bond insertion, which we call the "proton self-sufficient" (PSS) function of phenol. The PSS function of phenol indicates that the substrates with and without proton reservoirs will lead to different C-H bond insertion products.

Electrolysis-induced protonation of VO2 thin film transistor for the metal-insulator phase modulation

NASA Astrophysics Data System (ADS)

Katase, Takayoshi; Endo, Kenji; Ohta, Hiromichi

2016-02-01

Compared to state-of-the-art modulation techniques, protonation is the most ideal to control the electrical and optical properties of transition metal oxides (TMOs) due to its intrinsic non-volatile operation. However, the protonation of TMOs is not typically utilized for solid-state devices because of imperative high-temperature annealing treatment in hydrogen source. Although one solution for room temperature (RT) protonation of TMOs is liquid-phase electrochemistry, it is unsuited for practical purposes due to liquid-leakage problem. Herein we demonstrate solid-state RT-protonation of vanadium dioxide (VO2), which is a well-known thermochromic TMO. We fabricated the three terminal thin-film-transistor structure on an insulating VO2 film using a water-infiltrated nanoporous glass, which serves as a solid electrolyte. For gate voltage application, water electrolysis and protonation/deprotonation of VO2 film surface occurred, leading to reversible metal-insulator phase conversion of ~11-nm-thick VO2 layer. The protonation was clearly accompanied by the structural change from an insulating monoclinic to a metallic tetragonal phase. Present results offer a new route for the development of electro-optically active solid-state devices with TMO materials by engineering RT protonation.

DIFFERENTIATION OF AURANTII FRUCTUS IMMATURUS AND FRUCTUS PONICIRI TRIFOLIATAE IMMATURUS BY FLOW-INJECTION WITH ULTRAVIOLET SPECTROSCOPIC DETECTION AND PROTON NUCLEAR MAGNETIC RESONANCE USING PARTIAL LEAST-SQUARES DISCRIMINANT ANALYSIS.

PubMed

Zhang, Mengliang; Zhao, Yang; Harrington, Peter de B; Chen, Pei

2016-03-01

Two simple fingerprinting methods, flow-injection coupled to ultraviolet spectroscopy and proton nuclear magnetic resonance, were used for discriminating between Aurantii fructus immaturus and Fructus poniciri trifoliatae immaturus . Both methods were combined with partial least-squares discriminant analysis. In the flow-injection method, four data representations were evaluated: total ultraviolet absorbance chromatograms, averaged ultraviolet spectra, absorbance at 193, 205, 225, and 283 nm, and absorbance at 225 and 283 nm. Prediction rates of 100% were achieved for all data representations by partial least-squares discriminant analysis using leave-one-sample-out cross-validation. The prediction rate for the proton nuclear magnetic resonance data by partial least-squares discriminant analysis with leave-one-sample-out cross-validation was also 100%. A new validation set of data was collected by flow-injection with ultraviolet spectroscopic detection two weeks later and predicted by partial least-squares discriminant analysis models constructed by the initial data representations with no parameter changes. The classification rates were 95% with the total ultraviolet absorbance chromatograms datasets and 100% with the other three datasets. Flow-injection with ultraviolet detection and proton nuclear magnetic resonance are simple, high throughput, and low-cost methods for discrimination studies.

Kinetic Analysis of Competitive Electrocatalytic Pathways: New Insights into Hydrogen Production with Nickel Electrocatalysts

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

Wiedner, Eric S.; Brown, Houston J.; Helm, Monte L.

2016-01-20

The hydrogen production electrocatalyst Ni(PPh2NPh2)22+ (1) is capable of traversing multiple electrocatalytic pathways. When using dimethylformamidium, DMF(H)+, the mechanism of formation of H2 catalyzed by 1 changes from an ECEC to an EECC mechanism as the potential approaches the Ni(I/0) couple. Two recent electrochemical methods, current-potential analysis and foot-of-the-wave analysis (FOWA), were performed on 1 to measure the detailed chemical kinetics of the competing ECEC and EECC pathways. A sensitivity analysis was performed on the electrochemical methods using digital simulations to gain a better understanding of their strengths and limitations. Notably, chemical rate constants were significantly underestimated when not accountingmore » for electron transfer kinetics, even when electron transfer was fast enough to afford a reversible non-catalytic wave. The EECC pathway of 1 was found to be faster than the ECEC pathway under all conditions studied. Using buffered DMF: DMF(H)+ mixtures led to an increase in the catalytic rate constant (kobs) of the EECC pathway, but kobs for the ECEC pathway did not change when using buffered acid. Further kinetic analysis of the ECEC path revealed that added base increases the rate of isomerization of the exo-protonated Ni(0) isomers to the catalytically active endo-isomers, but decreases the net rate of protonation of Ni(I). FOWA on 1 did not provide accurate rate constants due to incomplete reduction of the exo-protonated Ni(I) intermediate at the foot of the wave, but FOWA could be used to estimate the reduction potential of this previously undetected intermediate. This research was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences. Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.« less

Positive Feedback Amplifies the Response of Mitochondrial Membrane Potential to Glucose Concentration in Clonal Pancreatic Beta Cells.

PubMed

Gerencser, Akos A; Mookerjee, Shona A; Jastroch, Martin; Brand, Martin D

2017-05-01

Analysis of the cellular mechanisms of metabolic disorders, including type 2 diabetes mellitus, is complicated by the large number of reactions and interactions in metabolic networks. Metabolic control analysis with appropriate modularization is a powerful method for simplifying and analyzing these networks. To analyze control of cellular energy metabolism in adherent cell cultures of the INS-1 832/13 pancreatic β-cell model we adapted our microscopy assay of absolute mitochondrial membrane potential (ΔψM) to a fluorescence microplate reader format, and applied it in conjunction with cell respirometry. In these cells the sensitive response of ΔψM to extracellular glucose concentration drives glucose-stimulated insulin secretion. Using metabolic control analysis we identified the control properties that generate this sensitive response. Force-flux relationships between ΔψM and respiration were used to calculate kinetic responses to ΔψM of processes both upstream (glucose oxidation) and downstream (proton leak and ATP turnover) of ΔψM. The analysis revealed that glucose-evoked ΔψM hyperpolarization is amplified by increased glucose oxidation activity caused by factors downstream of ΔψM. At high glucose, the hyperpolarized ΔψM is stabilized almost completely by the action of glucose oxidation, whereas proton leak also contributes to the homeostatic control of ΔψM at low glucose. These findings suggest a strong positive feedback loop in the regulation of β-cell energetics, and a possible regulatory role of proton leak in the fasting state. Analysis of islet bioenergetics from published cases of type 2 diabetes suggests that disruption of this feedback can explain the damaged bioenergetic response of β-cells to glucose. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy. Copyright © 2016 Elsevier B.V. All rights reserved.

SU-E-T-656: Quantitative Analysis of Proton Boron Fusion Therapy (PBFT) in Various Conditions

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

Yoon, D; Jung, J; Shin, H

2015-06-15

Purpose: Three alpha particles are concomitant of proton boron interaction, which can be used in radiotherapy applications. We performed simulation studies to determine the effectiveness of proton boron fusion therapy (PBFT) under various conditions. Methods: Boron uptake regions (BURs) of various widths and densities were implemented in Monte Carlo n-particle extended (MCNPX) simulation code. The effect of proton beam energy was considered for different BURs. Four simulation scenarios were designed to verify the effectiveness of integrated boost that was observed in the proton boron reaction. In these simulations, the effect of proton beam energy was determined for different physical conditions,more » such as size, location, and boron concentration. Results: Proton dose amplification was confirmed for all proton beam energies considered (< 96.62%). Based on the simulation results for different physical conditions, the threshold for the range in which proton dose amplification occurred was estimated as 0.3 cm. Effective proton boron reaction requires the boron concentration to be equal to or greater than 14.4 mg/g. Conclusion: We established the effects of the PBFT with various conditions by using Monte Carlo simulation. The results of our research can be used for providing a PBFT dose database.« less

Proton transport through aqueous Nafion membrane

NASA Astrophysics Data System (ADS)

Son, D. N.; Kasai, H.

2009-08-01

We introduce a new model for proton transport through a single proton-conducting channel of an aqueous Nafion membrane based on a mechanism in which protons move under electrostatic effect provided by the sulfonate ( SO3 -groups of the Nafion side chains, the spin effect of active components, the hydrogen bonding effect with water molecules, and the screening effect of water media. This model can describe the proton transport within various levels of humidification ranging from the low humidity to the high humidity as a function of operating temperature. At low humidity, this model approaches to the so-called surface mechanism, while at high humidity, it approaches the well-known Grotthuss one. Proton motion is considered as the transfer from cluster to cluster under a potential energy. A proton-proton interaction is comprised in the calculation. Using Green function method, we obtained the proton current as a function of the Nafion membrane temperature. We found that the lower the temperature, the higher the proton current transfer through the Nafion membrane in low temperatures compared to the critical point 10K, which separates magnetic regime from non-magnetic regime. The increasing of proton current at very low temperatures is attributed to the spin effect. As the membrane temperature is higher than 40 ° C , the decreasing of proton current is attributed to the loss of water uptake and the polymer contraction. The results of this study are qualitatively in good agreement with experiments. The expression for the critical temperature is also presented as a function of structural and tunable parameters, and interpreted by experimental data. in here

Research activities at the Loma Linda University and Proton Treatment Facility--an overview

NASA Technical Reports Server (NTRS)

Nelson, G. A.; Green, L. M.; Gridley, D. S.; Archambeau, J. O.; Slater, J. M.

2001-01-01

The Loma Linda University (LLU) Radiobiology Program coordinates basic research and proton beam service activities for the university and extramural communities. The current focus of the program is on the biological and physical properties of protons and the operation of radiobiology facilities for NASA-sponsored projects. The current accelerator, supporting facilities and operations are described along with a brief review of extramural research projects supported by the program. These include space craft electronic parts and shielding testing as well as tumorigenesis and animal behavior experiments. An overview of research projects currently underway at LLU is also described. These include: 1) acute responses of the C57Bl/6 mouse immune system, 2) modulation of gene expression in the nematode C. elegans and rat thyroid cells, 3) quantitation of dose tolerance in rat CNS microvasculature, 4) behavioral screening of whole body proton and iron ion-irradiated C57Bl/6 mice, and 5) investigation of the role of cell integration into epithelial structures on responses to radiation.

Evidence for involvement of uncoupling proteins in cerebral mitochondrial oxidative phosphorylation deficiency of rats exposed to 5,000 m high altitude.

PubMed

Xu, Yu; Liu, Yuliang; Xia, Chen; Gao, Pan; Liu, Jun-Ze

2013-02-01

The present study aimed to investigate the change of proton leak and discuss the role of cerebral uncoupling proteins (UCPs) and its regulatory molecules non-esterified fatty acid (NEFA) in high altitude mitochondrial oxidative phosphorylation deficiency. The model group animals were exposed to acute high altitude hypoxia, and the mitochondrial respiration, protein leak, UCPs abundance/activity and cerebral NEFA concentration were measured. We found that in the model group, cerebral mitochondrial oxidative phosphorylation was severely impaired with decreased ST3 respiration rate and ATP pool. Proton leak kinetics curves demonstrated an increase in proton leak; GTP binding assay pointed out that total cerebral UCPs activity significantly increased; Q-PCR and western blot showed upregulated expression of UCP4 and UCP5. Moreover, cerebral NEFA concentration increased. In conclusion, UCPs mediated proton leak is closely related to cerebral mitochondria oxidative phosphorylation deficiency during acute high altitude hypoxia and NEFA is involved in this signaling pathway.

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.

Qualitative comparison of bremsstrahlung X-rays and 800 MeV protons for tomography of urania fuel pellets

DOE PAGES

Morris, Christopher L.; Bourke, Mark A.; Byler, Darrin D.; ...

2013-02-11

We present an assessment of x-rays and proton tomography as tools for studying the time dependence of the development of damage in fuel rods. Also, we show data taken with existing facilities at Los Alamos National Laboratory that support this assessment. Data on surrogate fuel rods has been taken using the 800 MeV proton radiography (pRad) facility at the Los Alamos Neutron Science Center (LANSCE), and with a 450 keV bremsstrahlung X-ray tomography facility. The proton radiography pRad facility at LANSCE can provide good position resolution (<70 μm has been demonstrate, 20 μm seems feasible with minor changes) for tomographymore » on activated fuel rods. Bremsstrahlung x-rays may be able to provide better than 100 μm resolution but further development of sources, collimation and detectors is necessary for x-rays to deal with the background radiation for tomography of activated fuel rods.« less

Measurement of the high-energy gamma-ray emission from the Moon with the Fermi Large Area Telescope

DOE PAGES

Ackermann, M.; Ajello, M.; Albert, A.; ...

2016-04-08

We have measured the gamma-ray emission spectrum of the Moon using the data collected by the Large Area Telescope onboard the Fermi satellite during its first seven years of operation, in the energy range from 30 MeV up to a few GeV. We have also studied the time evolution of the flux, finding a correlation with the solar activity. We have developed a full Monte Carlo simulation describing the interactions of cosmic rays with the lunar surface. The results of the present analysis can be explained in the framework of this model, where the production of gamma rays is duemore » to the interactions of cosmic-ray proton and helium nuclei with the surface of the Moon. Lastly, we have used our simulation to derive the cosmic-ray proton and helium spectra near Earth from the Moon gamma-ray data.« less

Assay of Plasma Membrane H+-ATPase in Plant Tissues under Abiotic Stresses.

PubMed

Janicka, Małgorzata; Wdowikowska, Anna; Kłobus, Grażyna

2018-01-01

Plasma membrane (PM) H + -ATPase, which generates the proton gradient across the outer membrane of plant cells, plays a fundamental role in the regulation of many physiological processes fundamental for growth and development of plants. It is involved in the uptake of nutrients from external solutions, their loading into phloem and long-distance transport, stomata aperture and gas exchange, pH homeostasis in cytosol, cell wall loosening, and cell expansion. The crucial role of the enzyme in resistance of plants to abiotic and biotic stress factors has also been well documented. Such great diversity of physiological functions linked to the activity of one enzyme requires a suitable and complex regulation of H + -ATPase. This regulation comprises the transcriptional as well as post-transcriptional levels. Herein, we describe the techniques that can be useful for the analysis of the plasma membrane proton pump modifications at genetic and protein levels under environmental factors.

Measurement of the High-Energy Gamma-Ray Emission from the Moon with the Fermi Large Area Telescope

NASA Technical Reports Server (NTRS)

Ackermann, M.; Ajello, M.; Albert, A.; Atwood, W. B.; Baldini, L.; Barbiellini, G.; Bastieri, D.; Bellazzini, R.; Bissaldi, E.; Blandford, R. D.;

Hydrogen bond disruption in DNA base pairs from (14)C transmutation.

PubMed

Sassi, Michel; Carter, Damien J; Uberuaga, Blas P; Stanek, Christopher R; Mancera, Ricardo L; Marks, Nigel A

2014-09-04

Recent ab initio molecular dynamics simulations have shown that radioactive carbon does not normally fragment DNA bases when it decays. Motivated by this finding, density functional theory and Bader analysis have been used to quantify the effect of C → N transmutation on hydrogen bonding in DNA base pairs. We find that (14)C decay has the potential to significantly alter hydrogen bonds in a variety of ways including direct proton shuttling (thymine and cytosine), thermally activated proton shuttling (guanine), and hydrogen bond breaking (cytosine). Transmutation substantially modifies both the absolute and relative strengths of the hydrogen bonding pattern, and in two instances (adenine and cytosine), the density at the critical point indicates development of mild covalent character. Since hydrogen bonding is an important component of Watson-Crick pairing, these (14)C-induced modifications, while infrequent, may trigger errors in DNA transcription and replication.

A simple electric circuit model for proton exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Lazarou, Stavros; Pyrgioti, Eleftheria; Alexandridis, Antonio T.

A simple and novel dynamic circuit model for a proton exchange membrane (PEM) fuel cell suitable for the analysis and design of power systems is presented. The model takes into account phenomena like activation polarization, ohmic polarization, and mass transport effect present in a PEM fuel cell. The proposed circuit model includes three resistors to approach adequately these phenomena; however, since for the PEM dynamic performance connection or disconnection of an additional load is of crucial importance, the proposed model uses two saturable inductors accompanied by an ideal transformer to simulate the double layer charging effect during load step changes. To evaluate the effectiveness of the proposed model its dynamic performance under load step changes is simulated. Experimental results coming from a commercial PEM fuel cell module that uses hydrogen from a pressurized cylinder at the anode and atmospheric oxygen at the cathode, clearly verify the simulation results.

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.

Electronic properties of deep-level defects in proton irradiated AlGaAs-GaAs solar cells

NASA Technical Reports Server (NTRS)

Li, S. S.

1981-01-01

Deep level transient spectroscopy and capacitance voltage techniques as well as analysis of the forward current voltage (I-V) characteristics and SEM-EIC data were carried out for proton irradiated GaAs solar cells over a wide range of proton energies and proton fluences. Defect and recombination parameters such as defect energy levels and density, carrier capture cross sections and lifetimes as well as diffusion lengths in the undoped n-GaAs LPE layers were determined. Good correlation between these defect parameters and solar cell performance parameters was obtained for GaAs solar cells irradiated by 200 and 290 KeV protons. It was found that 200 to 290 KeV protons will produce the most defects and damages to the GaAs solar cell structure used. The influence of the low temperature (200 to 400 C) periodic thermal annealing on the deep level defects and the performance of the 200 KeV proton irradiated cells is discussed.

Comparative analysis of properties of channels of deuteron and tritium production in {sup 16}Op collisions at a projectile momentum of 3.25 GeV/c per nucleon

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

Olimov, K., E-mail: olimov@uzsci.net; Glagolev, V. V.; Gulamov, K. G.

2014-12-15

The results of a comparative analysis of channels involving the inclusive production of deuterons and tritons in {sup 16}Op collisions at a projectile momentum of 3.25 GeV/c per nucleon are presented. The mechanisms governing proton, deuteron, and triton production in the fragmentation of oxygen nuclei are found to be independent. It is shown that the observed proton-multiplicity correlations are associated predominantly with the character of the primary event of a proton-nucleon collision in {sup 16}Op interactions. It is found that, in reactions involving triton production, the contributions of processes leading to an increase in the mean proton multiplicity (n →more » p + π{sup −} and np → pn) and processes leading to its decrease (p → n + π{sup +}) compensate each other.« less

Delayed persistence of giant-nucleated cells induced by X-ray and proton irradiation in the progeny of replicating normal human f ibroblast cells

NASA Astrophysics Data System (ADS)

Almahwasi, A. A.; Jeynes, J. C.; Merchant, M. J.; Bradley, D. A.; Regan, P. H.

2017-08-01

Ionising radiation can induce giant-nucleated cells (GCs) in the progeny of irradiated populations, as demonstrated in various cellular systems. Most in vitro studies have utilised quiescent cancerous or normal cell lines but it is not clear whether radiation-induced GCs persist in the progeny of normal replicated cells. In the current work we show persistent induction of GCs in the progeny of normal human-diploid skin fibroblasts (AG1522). These cells were originally irradiated with a single equivalent clinical dose of 0.2, 1 or 2 Gy of either X-ray or proton irradiation and maintained in an active state for various post-irradiation incubation interval times before they were replated for GC analysis. The results demonstrate that the formation of GCs in the progeny of X-ray or proton irradiated cells was increased in a dose-dependent manner when measured 7 days after irradiation and this finding is in agreement with that reported for the AG1522 cells using other radiation qualities. For the 1 Gy X-ray doses it was found that the GC yield increased continually with time up to 21 days post-irradiation. These results can act as benchmark data for such work and may have important implications for studies aimed at evaluating the efficacy of radiation therapy and in determining the risk of delayed effects particularly when applying protons.

Co-regulation of dark and light reactions in three biochemical subtypes of C(4) species.

PubMed

Kiirats, Olavi; Kramer, David M; Edwards, Gerald E

2010-08-01

Regulation of light harvesting in response to changes in light intensity, CO(2) and O(2) concentration was studied in C(4) species representing three different metabolic subtypes: Sorghum bicolor (NADP-malic enzyme), Amaranthus edulis (NAD-malic enzyme), and Panicum texanum (PEP-carboxykinase). Several photosynthetic parameters were measured on the intact leaf level including CO(2) assimilation rates, O(2) evolution, photosystem II activities, thylakoid proton circuit and dissipation of excitation energy. Gross rates of O(2) evolution (J(O)₂'), measured by analysis of chlorophyll fluorescence), net rates of O(2) evolution and CO(2) assimilation responded in parallel to changes in light and CO(2) levels. The C(4) subtypes had similar energy requirements for photosynthesis since there were no significant differences in maximal quantum efficiencies for gross rates of O(2) evolution (average value = 0.072 O(2)/quanta absorbed, approximately 14 quanta per O(2) evolved). At saturating actinic light intensities, when photosynthesis was suppressed by decreasing CO(2), ATP synthase proton conductivity (g (H) (+)) responded strongly to changes in electron flow, decreasing linearly with J(O)₂', which was previously observed in C(3) plants. It is proposed that g (H) (+) is controlled at the substrate level by inorganic phosphate availability. The results suggest development of nonphotochemical quenching in C(4) plants is controlled by a decrease in g (H) (+), which causes an increase in proton motive force by restricting proton efflux from the lumen, rather than by cyclic or pseudocyclic electron flow.

Particle irradiation induces FGF2 expression in normal human lens cells

NASA Technical Reports Server (NTRS)

Chang, P. Y.; Bjornstad K, A.; Chang, E.; McNamara, M.; Barcellos-Hoff, M. H.; Lin, S. P.; Aragon, G.; Polansky, J. R.; Lui, G. M.; Blakely, E. A.

2000-01-01

Particle Irradiation Induces FGF2 Expression in Normal Human Lens Cells. Particle radiations, including both proton and helium-ion beams, have been used to successfully treat choroidal melanoma, but with the complication of radiation-induced cataract. We have investigated a role for radiation-induced changes in the expression of basic fibroblast growth factor (FGF2) gene expression as part of the mechanism(s) underlying lens cell injury associated with cataract. Normal human lens epithelial (HLE) cells were cultured in vitro on extracellular matrix (ECM) originated from bovine corneal endothelial cells. This study reports evidence for rapid but transient induction of FGF2 transcripts, an increase of between 5- and 8-fold, within 0.5 h after exposure to particle radiation, followed by another wave of increased transcription at 2-3 h postirradiation. Immunofluorescence results confirm the enhanced levels of FGF2 protein rapidly after exposure to protons or helium ions, followed by another wave of increased activity unique to helium at 6 h postirradiation. This second wave of increased immunoreactivity was not observed in the proton-irradiated samples. Total FGF2 protein analysis after helium-ion exposures shows induced expression of three FGF2 isoforms, with an increase of up to 2-fold in the 18-kDa low-molecular-weight species. Studies of the effects of protons on individual FGF2 protein isoforms are in progress. Several mechanisms involving a role for FGF2 in radiation-induced cataract are discussed.

Photoluminescence of radiation-induced color centers in lithium fluoride thin films for advanced diagnostics of proton beams

NASA Astrophysics Data System (ADS)

Piccinini, M.; Ambrosini, F.; Ampollini, A.; Picardi, L.; Ronsivalle, C.; Bonfigli, F.; Libera, S.; Nichelatti, E.; Vincenti, M. A.; Montereali, R. M.

2015-06-01

Systematic irradiation of thermally evaporated 0.8 μm thick polycrystalline lithium fluoride films on glass was performed by proton beams of 3 and 7 MeV energies, produced by a linear accelerator, in a fluence range from 1011 to 1015 protons/cm2. The visible photoluminescence spectra of radiation-induced F2 and F3+ laser active color centers, which possess almost overlapping absorption bands at about 450 nm, were measured under laser pumping at 458 nm. On the basis of simulations of the linear energy transfer with proton penetration depth in LiF, it was possible to obtain the behavior of the measured integrated photoluminescence intensity of proton irradiated LiF films as a function of the deposited dose. The photoluminescence signal is linearly dependent on the deposited dose in the interval from 103 to about 106 Gy, independently from the used proton energies. This behavior is very encouraging for the development of advanced solid state radiation detectors based on optically transparent LiF thin films for proton beam diagnostics and two-dimensional dose mapping.

Quantum-mechanical analysis of amino acid residues function in the proton transport during F0F1-ATP synthase catalytic cycle

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Standardisation of the ion beam facility at Chandigarh cyclotron for simultaneous PIXE and PESA analysis

NASA Astrophysics Data System (ADS)

Verma, Shivcharan; Mohanty, Biraja P.; Singh, Karn P.; Kumar, Ashok

2018-02-01

The proton beam facility at variable energy cyclotron (VEC) Panjab University, Chandigarh, India is being used for Particle Induced X-ray Emission (PIXE) analysis of different environmental, biological and industrial samples. The PIXE method, however, does not provide any information of low Z elements like carbon, nitrogen, oxygen and fluorine. As a result of the increased need for rapid and multi-elemental analysis of biological and environmental samples, the PIXE facility was upgraded and standardized to facilitate simultaneous measurements using PIXE and Proton Elastic Scattering Analysis (PESA). Both PIXE and PESA techniques were calibrated and standardized individually. Finally, the set up was tested by carrying out simultaneous PIXE and PESA measurements using a 2 mm diameter proton beam of 2.7 MeV on few multilayered thin samples. The results obtained show excellent agreement between PIXE and PESA measurements and confirm adequate sensitivity and precision of the experimental set up.

A molecular dynamics study of the BACE1 conformational change from Apo to closed form induced by hydroxyethylamine derived compounds.

PubMed

Gueto-Tettay, Carlos; Zuchniarz, Joshua; Fortich-Seca, Yeyson; Gueto-Tettay, Luis Roberto; Drosos-Ramirez, Juan Carlos

2016-11-01

BACE1 is an aspartyl protease which is a therapeutic target for Alzheimer's disease (AD) because of its participation in the rate-limiting step in the production of Aβ-peptide, the accumulation of which produces senile plaques and, in turn, the neurodegenerative effects associated with AD. The active site of this protease is composed in part by two aspartic residues (Asp93 and Asp289). Additionally, the catalytic site has been found to be covered by an antiparallel hairpin loop called the flap. The dynamics of this flap are fundamental to the catalytic function of the enzyme. When BACE1 is inactive (Apo), the flap adopts an open conformation, allowing a substrate or inhibitor to access the active site. Subsequent interaction with the ligand induces flap closure and the stabilization of the macromolecular complex. Further, the protonation state of the aspartic dyad is affected by the chemical nature of the species entering the active site, so that appropriate selection of protonation states for the ligand and the catalytic residues will permit the elucidation of the inhibitory pathway for BACE1. In the present study, comparative analysis of different combinations of protonation states for the BACE1-hydroxyethylamine (HEA) system is reported. HEAs are potent inhibitors of BACE1 with favorable pharmacological and kinetic properties, as well as oral bioavailability. The results of Molecular Dynamics (MD) simulations and population density calculations using 8 different parameters demonstrate that the LnAsp289 configuration (HEA with a neutral amine and the Asp289 residue protonated) is the only one which permits the expected conformational change in BACE1, from apo to closed form, after flap closure. Additionally, differences in their capacities to establish and maintain interactions with residues such as Asp93, Gly95, Thr133, Asp289, Gly291, and Asn294 during this step allow differentiation among the inhibitory activities of the HEAs. The results and methodology here reported will serve to elucidate the inhibitory pathway of other families of compounds that act as BACE1 inhibitors, as well as the design of better leader compounds for the treatment of AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Light-induced spatial control of pH-jump reaction at smart gel interface.

PubMed

Techawanitchai, Prapatsorn; Ebara, Mitsuhiro; Idota, Naokazu; Aoyagi, Takao

2012-11-01

We proposed here a 'smart' control of an interface movement of proton diffusion in temperature- and pH-responsive hydrogels using a light-induced spatial pH-jump reaction. A photoinitiated proton-releasing reaction of o-nitrobenzaldehyde (NBA) was integrated into poly(N-isopropylacrylamide-o-2-carboxyisopropylacrylamide) (P(NIPAAm-co-CIPAAm)) hydrogels. NBA-integrated hydrogels demonstrated quick release of proton upon UV irradiation, allowing the pH inside the gel to decrease below the pK(a) of P(NIPAAm-co-CIPAAm) within a minute. The NBA-integrated gel was shown to shrink rapidly upon UV irradiation without polymer "skin layer" formation due to a uniform decrease of pH inside the gel. Spatial control of gel shrinking was also created by irradiating UV light to a limited region of the gel through a photomask. The interface of proton diffusion ("active interface") gradually moved toward non-illuminated area. The apparent position of "active interface", however, did not change remarkably above the LCST, while protons continuously diffused outward direction. This is because the "active interface" also moved inward direction as gel shrank above the LCST. As a result, slow movement of the apparent interface was observed. The NBA-integrated gel was also successfully employed for the controlled release of an entrapped dextran in a light controlled manner. This system is highly promising as smart platforms for triggered and programmed transportation of drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

Ulysses charged particle measurements between 1 and 5 AU from the sun.

PubMed

Page, D E; Smith, E J; Wenzel, K P

1994-10-01

Proton fluxes obtained by two instruments carried on the ESA/NASA Ulysses spacecraft are reported for the period from launch in October 1990 till Jupiter encounter in February 1992. Proton energy ranges are 24-59, 71-99, 130-320, 320-2100 and > 2100 MeV. The Sun was very active during this period, the events of March 1991 being some of the largest of the solar cycle. The relationship between events on the Sun and the observed proton flux is discussed.

Proton electron nuclear double resonance from nitrosyl horse heart myoglobin: the role of His-E7 and Val-E11.

PubMed Central

Flores, M; Wajnberg, E; Bemski, G

2000-01-01

Electron nuclear double resonance (ENDOR) spectroscopy has been used to study protons in nitrosyl horse heart myoglobin (MbNO). (1)H ENDOR spectra were recorded for different settings of the magnetic field. Detailed analysis of the ENDOR powder spectra, using computer simulation, based on the "orientation-selection" principle, leads to the identification of the available protons in the heme pocket. We observe hyperfine interactions of the N(HisF8)-Fe(2+)-N(NO) complex with five protons in axial and with eight protons in the rhombic symmetry along different orientations, including those of the principal axes of the g-tensor. Protons from His-E7 and Val-E11 residues are identified in the two symmetries, rhombic and axial, exhibited by MbNO. Our results indicate that both residues are present inside the heme pocket and help to stabilize one particular conformation. PMID:10733988

Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable radiosensitizers

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

Cho, Jongmin, E-mail: jongmin.cho@okstate.edu

2016-08-15

Purpose: Gold nanoparticles (GNPs) are being investigated actively for various applications in cancer diagnosis and therapy. As an effort to improve the imaging of GNPs in vivo, the authors developed bimetallic hybrid Zn@Au NPs with zinc cores and gold shells, aiming to render them in vivo visibility through positron emission tomography (PET) after the proton activation of the zinc core as well as capability to induce radiosensitization through the secondary electrons produced from the gold shell when irradiated by various radiation sources. Methods: Nearly spherical zinc NPs (∼5-nm diameter) were synthesized and then coated with a ∼4.25-nm gold layer tomore » make Zn@Au NPs (∼13.5-nm total diameter). 28.6 mg of these Zn@Au NPs was deposited (∼100 μm thick) on a thin cellulose target and placed in an aluminum target holder and subsequently irradiated with 14.15-MeV protons from a GE PETtrace cyclotron with 5-μA current for 5 min. After irradiation, the cellulose matrix with the NPs was placed in a dose calibrator to assess the induced radioactivity. The same procedure was repeated with 8-MeV protons. Gamma ray spectroscopy using an high-purity germanium detector was conducted on a very small fraction (<1 mg) of the irradiated NPs for each proton energy. In addition to experimental measurements, Monte Carlo simulations were also performed with radioactive Zn@Au NPs and solid GNPs of the same size irradiated with 160-MeV protons and 250-kVp x-rays. Results: The authors measured 168 μCi of activity 32 min after the end of bombardment for the 14.15-MeV proton energy sample using the {sup 66}Ga setting on a dose calibrator; activity decreased to 2 μCi over a 24-h period. For the 8-MeV proton energy sample, PET imaging was additionally performed for 5 min after a 12-h delay. A 12-h gamma ray spectrum showed strong peaks at 511 keV (2.05 × 10{sup 6} counts) with several other peaks of smaller magnitude for each proton energy sample. PET imaging showed strong PET signals from mostly decaying {sup 66}Ga. The Monte Carlo results showed that radioactive Zn@Au NPs and solid GNPs provided similar characteristics in terms of their secondary electron spectra when irradiated. Conclusions: The Zn@Au NPs developed in this investigation have the potential to be used as PET-imageable radiosensitizers for radiotherapy applications as well as PET tracers for molecular imaging applications.« less