Proton Path Research Articles

Realistic simulations of the coupling between the protomotive force and the mechanical rotation of the F 0 -ATPase

The molecular origin of the action of the F(0) proton gradient-driven rotor presents a major puzzle despite significant structural advances. Although important conceptual models have provided guidelines of how such systems should work, it has been challenging to generate a structure-based molecular model using physical principles that will consistently lead to the unidirectional proton-driven rotational motion during ATP synthesis. This work uses a coarse-grained (CG) model to simulate the energetics of the F(0)-ATPase system in the combined space defined by the rotational coordinate and the proton transport (PTR) from the periplasmic side (P) to the cytoplasmic side (N). The model establishes the molecular origin of the rotation, showing that this effect is due to asymmetry in the energetics of the proton path rather than only the asymmetry of the interaction of the Asp on the c-ring helices and Arg on the subunit-a. The simulation provides a clear conceptual background for further exploration of the electrostatic basis of proton-driven mechanochemical systems.

Proton Delivery to Ferryl Heme in a Heme Peroxidase: Enzymatic Use of the Grotthuss Mechanism

We test the hypothesized pathway by which protons are passed from the substrate, ascorbate, to the ferryl oxygen in the heme enzyme ascorbate peroxidase (APX). The role of amino acid side chains and bound solvent is demonstrated. We investigated solvent kinetic isotope effects (SKIE) for the wild-type enzyme and several site-directed replacements of the key residues which form the proposed proton path. Kinetic constants for H(2)O(2)-dependent enzyme oxidation to Compound I, k(1), and subsequent reduction of Compound II, k(3), were determined in steady-state assays by variation of both H(2)O(2) and ascorbate concentrations. A high value of the SKIE for wild type APX ((D)k(3) = 4.9) as well as a clear nonlinear dependence on the deuterium composition of the solvent in proton inventory experiments suggest the simultaneous participation of several protons in the transition state for proton transfer. The full SKIE and the proton inventory data were modeled by applying Gross-Butler-Swain-Kresge theory to a proton path inferred from the known structure of APX. The model has been tested by constructing and determining the X-ray structures of the R38K and R38A variants and accounts for their observed SKIEs. This work confirms APX uses two arginine residues in the proton path. Thus, Arg38 and Arg172 have dual roles, both in the formation of the ferryl species and binding of ascorbate respectively and to facilitate proton transfer between the two.

Spatial resolution of proton tomography: Methods, initial phase space and object thickness

PurposeProton radiography and tomography was investigated since the early 1970s because of its low radiation dose, high density resolution and ability to image directly proton stopping power. However, spatial resolution is still a limiting factor and as a consequence experimental methods and image reconstruction should be optimized to improve position resolution. MethodsSpatial resolution of proton radiography and tomography is given by multiple Coloumb scattering (MCS) of the protons in the patient. In this paper we employ an improved MCS model to study the impact of various proton tomographic set-ups on the spatial resolution, such as different combinations of entrance and exit coordinate and angle measurements, respectively, initial particle energy and angular confusion of the incident proton field. ResultsIt was found that best spatial resolution is obtained by measuring in addition to the entrance and exit coordinates also the entrance and exit angles. However, by applying partial backprojection and by using a perfect proton fan beam a sufficient spatial resolution can be achieved with less experimental complexity (measuring only exit angles). It was also shown that it is essential to use the most probable proton trajectory to improve spatial resolution. A simple straight line connection for image reconstruction results in a spatial resolution which is not clinically sufficient. The percentage deterioration of spatial resolution due to the angular confusion of the incident proton field is less than the phase space in mrad. A clinically realistic proton beam with 10 mrad angular confusion results in a less than 10% loss of spatial resolution. ConclusionsClinically sufficient spatial resolution can be either achieved with a full measurement of entrance and exit coordinates and angles, but also by using a fan beam with small angular confusion and an exit angle measurement. It is necessary to use the most probable proton path for image reconstruction. A simple straight line connection is in general not sufficient. Increasing proton energy improves spatial resolution of an object of constant size. This should be considered in the design of proton therapy facilities.

Effects of Nafion ® ionomer and carbon particles on structure formation in a proton-exchange membrane fuel cell catalyst layer fabricated by the decal-transfer method

Cross-sectional visualizations of catalyst-coated membranes (CCMs) with various weight ratios of Nafion ® ionomer to carbon (N/C) in catalyst layers (CLs) of a proton-exchange membrane fuel cell were performed by a cross-section polishing method and scanning electron microscopy. Nitrogen physisorption measurements and energy-dispersive X-ray spectroscopy studies were also performed. The CL structure clearly affected the performance of the cell. Sufficient proton, electron, and oxygen paths are probably established in N/C 1.0, resulting in relatively higher cell performance per unit of Pt loading, whereas in N/C 3.0, insufficient transport paths were produced as a result of plugging of nanoscale pores by Nafion ® ionomer. However, the effective gas diffusivity in N/C 0.3 may be increased because of increases in porosity and pore diameter. Methods for controlling the macroscopic structural parameters of CLs during their manufacture are discussed; the thickness and porosity are determined mainly by the carbon and the ionomer, respectively.

Accuracy of the Most Likely Path Formalism in Inhomogeneous Phantoms

Proton computed tomography (pCT) has become a lively research field in medical imaging. Its importance lies in its ability to accurately locate the Bragg peak where the tumor is positioned for proton therapy treatment planning. The quality of the pCT image is primarily affected by the spatial resolution and relative electron density resolution. A measure of the spatial resolution is the amount of expected deviation of the actual proton paths from the theoretically derived paths based on the experimentally available data, the so-called most likely paths (MLPs). The MLPs are derived using the assumption that the object to be imaged is homogeneous water. Geant4 Monte Carlo simulations were used to simulate the actual proton paths through some inhomogeneous phantoms and were compared with MLP calculations. Statistical analyses were conducted to determine the spatial resolution of the protons in different phantoms as a function of inhomogeneity location, amount, and density.

Relationship among Microstructure, Ionomer Property and Proton Transport in Pseudo Catalyst Layers

The influence of the ionomer content on proton transport phenomena in the catalyst layers of a fuel cell was examined using pseudo catalyst layers (PCLs) consisting of the carbon support and the ionomer. Effective proton conductivity of the PCL increased with increasing ionomer content in both graphitized ketjen black (GKB) and ketjen black (KB) systems. It was found that the ionomer coverage θ and the Bruggeman factor γ, which is related to the tortuosity of the proton path in the PCL, did not depend on the ionomer content appreciably. In the GKB system, the volume fraction of the ionomer was the dominant factor of the difference in . However, the results of a water adsorption analysis with a heterogeneous Do-Do model suggested that the proton conductivity of the ionomer as bulk probably differs depending on the ionomer content in the KB system, though it was independent of the ionomer content in the GKB system. It was inferred that the interaction between functional groups on the KB surface and the ionomer weaken its water adsorbability. Consequently, the ionomer content would appear to affect not only structural parameters (i.e. γ and ) but also in the KB system.

MO-A-BRA-03: Promises and Perils of Proton Therapy

Proton therapy enables lowering of the integral dose to the patient due to the finite range of protons. The basis for the reduction of integral dose is the proton's Bragg peak which increases the dose deposited in the tumour while reduces that to the normal tissue at the distal side of the target volume. Protonradiotherapy reduces the volume of normal tissue exposed to low doses, which is clinically significant with respect to the risk of second malignancies. That risk is notably more pronounced for younger patients than older ones as younger patients are more at risk to future radiation induced cancers. However, proton therapy is less tolerant than photon therapy to uncertainties in both treatment planning and treatmentdelivery. For example, tissue inhomogeneity has a greater effect on protondose distributions than on photondose distributions. In planning proton therapy, the density of tissue along the proton path must be precisely determined and accounted for in order to obtain the required proton energy distribution to achieve the planned dose distribution in the patient. Failure to allow for a zone of higher density could result in a near zero dose in a distal segment of the target volume due to the reduced range of the protons. Conversely, neglecting to account for an air cavity upstream of the target volume would, for proton beams; result in a high dose being deposited in distal normal structures. Furthermore, motion and mis‐registration of the target volume with the radiation beams have far more severe consequences in proton therapy compared to photon therapy. If the target volumes are to be adequately irradiated, and adjacent OARs are to be protected in proton therapy, it is essential: that the causes and possible magnitudes of motion and misregistration are understood; that their possible consequences are understood; that measures are taken to minimize motion and mis‐registration to the extent possible and clinically warranted. It is almost impossible to get rid of all uncertainties in radiation therapy. Therefore, it is important to understand the sources of these uncertainties, quantify their magnitude, and develop mitigation and/or minimization strategies. In proton therapy margins are added to account for uncertainty sources that include; stopping power of tissues,dose calculation approximations, biological considerations, setup and anatomical variations, and internal movements of low and high density organs into the beam path. These margins reduce the benefit of proton therapy in treatment sites where the physical properties of protons could make a significant difference, such as lung cancer. The focus of this presentation is to; a) understand the potential sources of dosimetric uncertainties in proton therapy b) evaluate the impact of these uncertainties on the accuracy and conformity of dosedelivered to patients and c) suggest potential strategies that translate physical advantage of proton therapy into a maximized dosimetric benefit in the patient. Learning Objectives: 1. Describe the need for knowing potential sources of treatment planning and delivery uncertainties in proton therapy. 2. Summarize strategies to mitigate both proton therapy planning and delivery uncertainties.

TH-E-220-02: Spatial Resolution of Proton Tomography: Methods, Initial Phase Space and Object Thickness

Purpose: Protonradiography and tomography was investigated in the early 1970s because of its low radiation dose, high density resolution and ability to image directly protonstopping power.Spatial resolution is still a limiting factor. therefore experimental methods and image reconstruction should be optimized to improve position resolution. Methods: Spatial resolution of protontomography is given by multiple scattering(MCS) of the protons. We employ an improved MCS model to study the impact of proton tomographic set‐ups on spatial resolution, such as different combinations of entrance and exit coordinate and angle measurements, respectively, particle energy and angular confusion of the proton field. Results: It was found that best spatial resolution is obtained by measuring in addition to the entrance and exit coordinates the entrance and exit angles. By applying partial backprojection and a perfect proton fan beam a sufficient spatial resolution can be achieved with less experimental complexity. It was also shown that it is essential to use the most probable proton trajectory to improve spatial resolution. A simple straight line connection for image reconstruction results in a spatial resolution which is not clinically sufficient. The percentage deterioration of spatial resolution due to the angular confusion of the incident proton field is less than the phase space in mrad. Conclusions: Clinically sufficient spatial resolution can be either achieved with a full measurement of entrance and exit coordinates and angles, but also by using a fan beam with small angular confusion and an exit angle measurement. It is necessary to use the most probable proton path for image reconstruction. A simple straight line connection is in general not sufficient. Increasing proton energy improves spatial resolution of an object of constant size. This should be considered in the design of proton therapy facilities.

TH-E-220-01: Applications of Proton Radiography to Image Guided Proton Therapy - A Monte Carlo Study Involving the Most Likely Path Algorithm

Purpose: To optimize, through Monte Carlo simulation, a protonimagingsystem in localization of lungtumor motion and in quantification of proton range variations for image‐guidedproton therapy. Methods: The protonimagingsystem modeled consists of position detectors and a range telescope. The Monte Carlo N‐Particle eXtended (MCNPX) code with a particle‐tracking feature was used to evaluate imagingsystem performance in visualizing and quantifying proton radiological pathlength variations during respiration. Various proton path approximation algorithms were evaluated to improve the image quality and the optimal Most Likely Path (MLP) algorithm was selected. Tumor trajectories from protonradiographs were computed to image the real‐time respiratory phases and to provide feedback for gated treatment. The dosimetric gain of image‐guided gating treatment was quantified by calculating the equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) of organs at risk (OARs). Results: Image quality of protonradiograph with spatial resolution of ∼ 1.1 mm and range resolution of < 1 mm was achieved by applying the optimal MLP algorithm. Protonradiographs of two patient cases were reconstructed to determine tumor trajectories and radiological pathlength variations. The extracted tumor trajectories were within 1 mm of ground truth as determined from 4DCT. Utilizing tumor tracking, the margin was reduced for gated therapy. The dosimetric analysis shows that with image guidance, the EUD of OARs reduced by as much as 11 % and corresponding NTCP of organs at risk (OARs) reduced up to 16.5%. In our exploratory cases, we see potential gains from using protonradiography for lungcancer treatments. Conclusions: Simulation of protonradiograph suggests that protonimagingsystem can detecttumor motion and provide useful feedback information for gated treatment. The protonimagingsystem is potentially clinical useful for every‐day image‐guidedproton therapy to achieve better clinical outcome.

Inelastic scattering of electron and light ion beams in organic polymers

We have calculated the inelastic mean free path, stopping power, and energy-loss straggling of swift electron, proton, and α-particle beams in a broad incident energy range in four organic polymers: poly(methyl methacrylate) (PMMA), Kapton, polyacetylene (PA), and poly(2-vinylpyridine) (P2VP). These calculations have been done through a suitable description of their optical properties and its extension into the whole momentum and energy transfer excitation spectrum. For electrons, we take into account the exchange effect between the projectile and the target electrons, while the charge-state fractions have been considered for ions. Our results are compared with other models and with the available experimental data. An excellent agreement with experimental data is obtained in the case of proton and α-particle beams in Kapton and a reasonably good agreement has been achieved for electron beams in PMMA, Kapton, and PA. We have parameterized by means of simple analytical expressions our results for electron beams interacting with these four polymers, which can be easily implemented in Monte Carlo calculations.

Determination of the reduction depth of tungsten oxide thin films under the effect of proton irradiation

This work is devoted to experimental determination of the limiting reduction depth of tungsten oxide to metal by the measurement of volumetric variations in a thin film of WO3 under the effect of proton irradiation with an energy of 1.5 keV. The method of radiation-induced reduction of tungsten from WO3 can be used for preparation of conducting structures in a dielectric matrix and obtaining an inorganic mask for carrying out different ion-beam processes. It is shown experimentally that the effect of a proton beam with an energy of 1.5 keV provides complete reduction of a tungsten oxide layer up to 138 nm thick. The experimental ratio of the thickness of the reduced layer to the thickness of the starting oxide film was 0.31. It is shown that the limiting reduction depth of tungsten oxide is determined by the path of protons in tungsten.

Bragg peak prediction from quantitative proton computed tomography using different path estimates

This paper characterizes the performance of the straight-line path (SLP) and cubic spline path (CSP) as path estimates used in reconstruction of proton computed tomography (pCT). The GEANT4 Monte Carlo simulation toolkit is employed to simulate the imaging phantom and proton projections. SLP, CSP and the most-probable path (MPP) are constructed based on the entrance and exit information of each proton. The physical deviations of SLP, CSP and MPP from the real path are calculated. Using a conditional proton path probability map, the relative probability of SLP, CSP and MPP are calculated and compared. The depth dose and Bragg peak are predicted on the pCT images reconstructed using SLP, CSP, and MPP and compared with the simulation result. The root-mean-square physical deviations and the cumulative distribution of the physical deviations show that the performance of CSP is comparable to MPP while SLP is slightly inferior. About 90% of the SLP pixels and 99% of the CSP pixels lie in the 99% relative probability envelope of the MPP. Even at an imaging dose of ∼0.1 mGy the proton Bragg peak for a given incoming energy can be predicted on the pCT image reconstructed using SLP, CSP, or MPP with 1 mm accuracy. This study shows that SLP and CSP, like MPP, are adequate path estimates for pCT reconstruction, and therefore can be chosen as the path estimation method for pCT reconstruction, which can aid the treatment planning and range prediction of proton radiation therapy.

Crystallographic and online spectral evidence for role of conformational change and conserved water in cytochrome oxidase proton pump

Crystal structures in both oxidized and reduced forms are reported for two bacterial cytochrome c oxidase mutants that define the D and K proton paths, showing conformational change in response to reduction and the loss of strategic waters that can account for inhibition of proton transfer. In the oxidized state both mutants of the Rhodobacter sphaeroides enzyme, D132A and K362M, show overall structures similar to wild type, indicating no long-range effects of mutation. In the reduced state, the mutants show an altered conformation similar to that seen in reduced wild type, confirming this reproducible, reversible response to reduction. In the strongly inhibited D132A mutant, positions of residues and waters in the D pathway are unaffected except in the entry region close to the mutation, where a chloride ion replaces the missing carboxyl and a 2-Å shift in N207 results in loss of its associated water. In K362M, the methionine occupies the same position as the original lysine, but K362- and T359-associated waters in the wild-type structure are missing, likely accounting for the severe inhibition. Spectra of oxidized frozen crystals taken during X-ray radiation show metal center reduction, but indicate development of a strained configuration that only relaxes to a native form upon annealing. Resistance of the frozen crystal to structural change clarifies why the oxidized conformation is observable and supports the conclusion that the reduced conformation has functional significance. A mechanism is described that explains the conformational change and the incomplete response of the D-path mutant.

Physical Parameters Related to Quantify Quality of Effectiveness of Charged Particles at Lower Doses

Quality factors for protons and helium particles has determined for cell inactivation using linear energy transfer. The quality has also been investigated as a function for other physical parameters, such as mean free path and effective charge for protons and helium particles, for a better interpretation to the effectiveness of these charged particles in V79 cells. Explanation of quality is clearly illustrated in terms of the average dis-tance of energy deposition events in biological systems.

Microstructuring of Nd:YAG crystals by proton-beam writing

We report on the microstructuring of Nd:YAG crystals by direct proton-beam writing. Buried channel waveguides have been fabricated with full spatial control by the combined variation of crystal position and proton energy. The fluorescence images of the obtained structures have been used to evaluate the potential application of the fabricated structures for laser gain as well as to elucidate the mechanism at the basis of the refractive index increment induced at the end of the proton path. We have concluded that this increment is very likely a local enhancement in the electronic polarizability caused by nuclear collisions.

THE INFLUENCE OF DISSIPATION RANGE POWER SPECTRA AND PLASMA-WAVE POLARIZATION ON COSMIC-RAY SCATTERING MEAN FREE PATH

The influence of the polarization state and the dissipation range spectral steepening of slab plasma waves on the scattering mean free path of single-charged cosmic-ray particles is investigated in a turbulence model, where the crucial scattering of cosmic-ray particles with small pitch-angle cosines is caused by resonant cyclotron interactions with slab plasma waves. Analytical expressions for the mean free path of protons, antiprotons, negatrons, and positrons are derived for the case of constant frequency-independent magnetic helicity values ? and different values of the dissipation range spectral index k for characteristic interplanetary and interstellar plasma conditions. The positron mean free path is not affected by the dissipation range spectral index k as these particles can only cyclotron-resonate for rigidity values larger than R 0 = mpc = 938?MV. Proton and antiproton mean free paths are only slightly affected by the dissipation range spectral index k at small rigidities R < R 0. The negatron mean free path is severely affected by the dissipation range spectral index k at rigidities smaller than R 0. At high rigidities R R 0, all particle species approach the same power-law dependence R 2?s determined by the inertial range spectral index s = 5/3. The magnetic helicity value ? affects the value of the mean free path. At all rigidities, the ratio of the antiproton to proton mean free paths equals the constant (1 + ?)/(1 ? ?), which also agrees with the ratio of the negatron to the proton and positron mean free paths at relativistic rigidities. At relativistic rigidities the positron and proton mean free paths agree, as do the negatron and antiproton mean free paths.

On the use of a proton path probability map for proton computed tomography reconstructiona)

To describe a method to estimate the proton path in proton computed tomography (pCT) reconstruction, which is based on the probability of a proton passing through each point within an object to be imaged. Based on multiple Coulomb scattering and a semianalytically derived model, the conditional probability of a proton passing through each point within the object given its incoming and exit condition is calculated in a Bayesian inference framework, employing data obtained from Monte Carlo simulation using GEANT4. The conditional probability at all of the points in the reconstruction plane forms a conditional probability map and can be used for pCT reconstruction. From the generated conditional probability map, a most-likely path (MLP) and a 90% probability envelope around the most-likely path can be extracted and used for pCT reconstruction. The reconstructed pCT image using the conditional probability map yields a smooth pCT image with minor artifacts. pCT reconstructions obtained using the extracted MLP and the 90% probability envelope compare well to reconstructions employing the method of cubic spline proton path estimation. The conditional probability of a proton passing through each point in an object given its entrance and exit condition can be obtained using the proposed method. The extracted MLP and the 90% probability envelope match the proton path recorded in the GEANT4 simulation well. The generated probability map also provides a benchmark for comparing different path estimation methods.

Angular distribution of acoustic radiation created in water by a beam of accelerated protons

We present the results of experimental investigations into the hydroacoustic field of a source created by a beam of protons accelerated to an energy of 200 MeV. We obtain the angular distribution of the signal amplitude arising in the most intensively radiating area of the source, localized at the end of an ionized path of protons. We simulate the physical processes accompanying the passage of electrons in a water medium. The results of simulation calculations agree with the experimental data.

Binuclear Hexa- and Pentavalent Uranium Complexes with a Polypyrrolic Ligand: A Density Functional Study of Water- and Hydronium-Induced Reactions

Binuclear uranyl (VI) and (V) complexes of a Pacman-like polypyrrolic macrocycle (H(4)L) were investigated using relativistic density functional theory. The reactivity of the bis-uranyl(VI) complex (UO(2))(2)(L) (2a) was explored computationally. Although 2a has not been obtained experimentally, its structural analogue [(UO(2))(OH)K(THF)(2)(H(2)L(Me))] has been synthesized recently. The high reactive activity of 2a originates from its unique butterfly like cation-cation structure, containing an active O center with easily broken U-O bonding and having unsaturated coordination sites of uranium(VI) along the equatorial plane. The present study indicates that 2a can react with water (Path 3) and hydronium (Path 4), which lead to the formation of a series of complexes with a triangle-like O=U=O=U=O skeleton. Path 3 results in an unusual complex containing a combined cis-uranyl/trans-uranyl cation-cation structure, (cis-UO(2))(trans-UO(2))(H(2)O)(L) (4b), where the oxo atom of the trans-uranyl coordinates the uranium center of the cis-uranyl and the water bonds to the uranium of trans-uranyl in the equatorial plane. After a process of hydrogen transfer with an extremely low energy barrier (<1.5 kcal/mol), 4b is converted into a slightly more stable isomer (U(2)O(3))(OH)(2)(L) (4a), where two hydroxyl groups link to two uranium atoms, respectively. In conjunction with previous studies, the free energies of reactions of 2a induced by isomerization (Path 1), proton (Path 2), water (Path 3), and hydronium (Path 4) were calculated in the gas phase and aqueous solution. Solvation stabilizes the free energy of the formation reactions of the neutral complexes but destabilizes that of the charged complexes. In these reactions, three pairs of isomers were obtained for binuclear uranium(VI) complexes, but only the most stable in each pair exists for the binuclear uranium(V) analogues.

Determination of Distal Dose Edge in Human Phantom by Measuring Prompt Gamma Distribution: A Monte Carlo Study

The close relationship between the proton dose distribution and the distribution of prompt gammas generated by proton-induced nuclear interactions along the path of protons in a water phantom was demonstrated by means of both Monte Carlo simulations and limited experiments. In order to test the clinical applicability of the method for determining the distal dose edge in a human body, a human voxel model, constructed based on a body-composition-approximated physical phantom, was used, after which the MCNPX code was used to analyze the energy spectra and the prompt gamma yields from the major elements composing the human voxel model; finally, the prompt gamma distribution, generated from the voxel model and measured by using an array-type prompt gamma detection system, was calculated and compared with the proton dose distribution. According to the results, eective prompt gammas were produced mainly by oxygen, and the specific energy of the prompt gammas, allowing for selective measurement, was found to be 4.44 MeV. The results also show that the distal dose edge in the human phantom, despite the heterogeneous composition and the complicated shape, can be determined by measuring the prompt gamma distribution with an array-type detection system.