Information about the 12C(α,γ)16O reaction from the β-delayed proton decay of 17Ne

NASA Astrophysics Data System (ADS)

King, J. D.; Chow, J. C.; Morton, A. C.; Azuma, R. E.; Bateman, N.; Boyd, R. N.; Buchmann, L.; D'Auria, J. M.; Davinson, T.; Dombsky, M.; Galster, W.; Gete, E.; Giesen, U.; Iliadis, C.; Jackson, K. P.; Roy, G.; Shoppa, T.; Shotter, A.

1998-02-01

We are studying the β-delayed proton decay of 17Ne with the goal of determining the E2 part of the 12C(α,γ)16O cross section at energies relevant to helium burning in stars. We have determined branching ratios for proton and α-decay for states in 17F from 8.08 to 11.193 MeV. In addition, we have observed the break-up of the isobaric analogue state (IAS) at 11.193 MeV into three particles via two channels: proton decay to the 9.59 MeV state in 16O which breaks up into an α-particle plus 12C; and α-decay to the 2.365 MeV state in 13N which breaks up into a proton plus 12C. This is the first reported observation of the decay of the IAS to the 1- state in 16O at 9.59 MeV.

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

Schwartz, S. B.; Wrede, C.; Bennett, M. B.

Background: The Doppler broadening of gamma-ray peaks is due to nuclear recoil from beta-delayed nucleon emission can be used to measure the energies of the nucleons. This method has never been tested using beta-delayed proton emission or applied to a recoil heavier than A = 10. Purpose: To test and apply this Doppler broadening method using gamma-ray peaks from the P-26(beta p gamma)Al-25 decay sequence. Methods: A fast beam of P-26 was implanted into a planar Ge detector, which was used as a P-26 beta-decay trigger. The SeGA array of high-purity Ge detectors was used to detect gamma rays frommore » the P-26(beta p gamma)Al-25 decay sequence. Results: Radiative Doppler broadening in beta-delayed proton-gamma decay was observed for the first time. Moreover, the Doppler broadening analysis method was verified using the 1613-keV gamma-ray line for which the proton energies were previously known. The 1776-keV gamma ray de-exciting the 2720 keV Al-25 level was observed in P-26(beta p gamma)Al-25 decay for the first time and used to determine that the center-of-mass energy of the proton emission feeding the 2720-keV level is 5.1 +/- 1.0 (stat.) +/- 0.6 (syst.) MeV, corresponding to a Si-26 excitation energy of 13.3 +/- 1.0 (stat.) +/- 0.6 (syst.) MeV for the proton-emitting level. Conclusions: Finally, the Doppler broadening method has been demonstrated to provide practical measurements of the energies for beta-delayed nucleon emissions populating excited states of nuclear recoils at least as heavy as A = 25.« less

Beta decay of exotic TZ = -1, -2 nuclei: the interesting case of 56Zn

NASA Astrophysics Data System (ADS)

Orrigo, S. E. A.; Rubio, B.; Fujita, Y.; Blank, B.; Gelletly, W.; Agramunt, J.; Algora, A.; Ascher, P.; Bilgier, B.; Cáceres, L.; Cakirli, R. B.; Fujita, H.; Ganioğlu, E.; Gerbaux, M.; Giovinazzo, J.; Grévy, S.; Kamalou, O.; Kozer, H. C.; Kucuk, L.; Kurtukian-Nieto, T.; Molina, F.; Popescu, L.; Rogers, A. M.; Susoy, G.; Stodel, C.; Suzuki, T.; Tamii, A.; Thomas, J. C.

2014-03-01

The β decay properties of the Tz = -2, 56Zn isotope and other proton-rich nuclei in the fp-shell have been investigated in an experiment performed at GANIL. The ions were produced in fragmentation reactions and implanted in a double-sided silicon strip detector surrounded by Ge EXOGAM clovers. Preliminary results for 56Zn are presented .The 56Zn decay proceeds mainly by β delayed proton emission, but β delayed gamma rays were also detected. Moreover, the exotic β delayed gamma-proton decay was observed for the first time. The 56Zn half-life and the energy levels populated in the 56Cu daughter have been determined. Knowledge of the gamma de-excitation of the mirror states in 56Co and the comparison with the results of the mirror charge exchange process, the 56Fe(3He,t) reaction (where 56Fe has Tz = +2), were important in the interpretation of the 56Zn decay data. The absolute Fermi and Gamow-Teller strengths have been deduced.

Detailed characterization of low background β-delayed proton detector

NASA Astrophysics Data System (ADS)

Janasik, Molly; Friedman, Moshe; Budner, Tamas; Wrede, Chris

2017-09-01

In order to determine the rates of two important reactions for the astrophysical rapid proton (rp) capture process, a segmented, low background β-delayed proton detector has been built at NSCL. The detector is currently in the process of being optimized. A detailed characterization of the detector's Micromegas pad plane is being performed using measurements with a radioactive 55Fe x-ray calibration source. A fitting routine has been developed to extract the energy resolution from the spectra. First results of detector resolution with P10 gas will be presented. This work is supported by the U.S. National Science Foundation under Award Nos. PHY-1102511 and PHY- 1565546 and the U.S. Department of Energy, Office of Science, under Award No. DE-SC0016052.

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. )

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.

Delayed methotrexate elimination: Incidence, interaction with antacid drugs, and clinical consequences?

PubMed

Ranchon, Florence; Vantard, Nicolas; Henin, Emilie; Bachy, Emmanuel; Sarkozy, Clémentine; Karlin, Lionel; Bouafia-Sauvy, Fadhela; Gouraud, Aurore; Schwiertz, Verane; Bourbon, Estelle; Baudouin, Amandine; Caffin, Anne Gaelle; Vial, Thierry; Salles, Gilles; Rioufol, Catherine

2018-04-01

The aim of this retrospective cohort study was to investigate the incidence of delayed methotrexate elimination in patients treated with high-dose methotrexate (≥1 g/m 2 ) for haematological malignancy and to identify the impact of interacting drugs, especially proton-pump inhibitors (PPIs) and ranitidine. All patients treated with high-dose methotrexate over a 6 year period in the haematology department of the Lyon Sud University Hospital (Hospices Civils de Lyon, France) were included. Potential risk factors for delayed methotrexate elimination were tested in a generalized linear model by univariate analysis: patient age, gender, methotrexate dose, administration of PPI or ranitidine, and concomitant nephrotoxic drugs. A total of 412 cycles of methotrexate were administered to 179 patients. Proton-pump inhibitors were co-administered with methotrexate in 127 cycles and ranitidine in 192 cycles. Ninety-three cycles included no antacid drugs. A total of 918 plasma methotrexate assays were performed. Methotrexate concentrations were checked at 24 hours in 92% of cycles. Delayed methotrexate elimination was observed in 20.9% of cycles. A total of 63 cycles with delayed methotrexate elimination were only identified on plasma methotrexate measures at 72 hours: ie, plasma methotrexate was in the normal range at 24 and 48 hour post injection. Use of PPI/ranitidine or no antacid drugs did not increase risk of delayed elimination, with respectively delayed methotrexate elimination in 20.5%, 21.9%, and 19.4% of cycles (P = .89). Impaired baseline creatinine clearance showed significant association in univariate analysis. Fifteen patients showed grade 1 acute kidney injury, 1 grade 2, 2 grade 3, and none grade 4. For half of these cases, delayed methotrexate elimination was observed and the 2 grade 3 events appeared in patients treated with PPIs. This retrospective study suggests that there is no association between concomitant use of proton-pump inhibitors (pantoprazole and esomeprazole) or ranitidine and delayed methotrexate elimination. Copyright © 2017 John Wiley & Sons, Ltd.

Experimental study of β-delayed proton decay of Al23 for nucleosynthesis in novae

NASA Astrophysics Data System (ADS)

Saastamoinen, A.; Trache, L.; Banu, A.; Bentley, M. A.; Davinson, T.; Hardy, J. C.; Iacob, V. E.; McCleskey, M.; Roeder, B. T.; Simmons, E.; Tabacaru, G.; Tribble, R. E.; Woods, P. J.; Äystö, J.

2011-04-01

The β-delayed γ and proton decay of Al23 has been studied with an alternative detector setup at the focal plane of the momentum achromat recoil separator MARS at Texas A&M University. We could detect protons down to an energy of 200 keV and determine the corresponding branching ratios. Contrary to results of previous β-decay studies, no strong proton intensity from the decay of the isobaric analog state (IAS) of the Al23 ground state at Ex=7803 keV in Mg23 was observed. Instead we assign the observed low-energy group Ep,c.m.=206 keV to the decay from a state that is 16 keV below the IAS. We measured both proton and gamma branches from the decay of this state at Ex=7787 keV in Mg23, which is a very rare case in the literature. Combining our data with its measured lifetime, we determine its resonance strength to be ωγ=1.4-0.4+0.5 meV. The value is in agreement with older direct measurements, but disagrees with a recent direct measurement. This state is the most important resonance for the radiative proton capture Na22(p,γ)Mg23 in some astrophysical environments, such as novae.

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.

WE-G-BRE-07: Proton Therapy Enhanced by Tumor-Targeting Gold Nanoparticles: A Pilot in Vivo Experiment at The Proton Therapy Center at MD Anderson Cancer Center

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

Wolfe, T; Grant, J; Wolfe, A

Purpose: Assess tumor-growth delay and survival in a mouse model of prostate cancer treated with tumor-targeting gold nanoparticles (AuNPs) and proton therapy. Methods: We first examined the accumulation of targeting nanoparticles within prostate tumors by imaging AuNPs with ultrasound-guided photoacoustics at 24h after the intravenous administration of goserelin-conjugated AuNPs (gAuNP) in three mice. Nanoparticles were also imaged at the cellular level with TEM in PC3 cells incubated with gAuNP for 24h. Pegylated AuNPs (pAuNP) were also imaged in vivo and in vitro for comparison. PC3 cells were then implanted subcutaneously in nude mice; 51mice with 8–10mm tumors were included. AuNPsmore » were injected intravenously at 0.2%w/w final gold concentration 24h before irradiation. A special jig was designed to facilitate tumor irradiation perpendicular to the proton beam. Proton energy was set to 180MeV, the radiation field was 18×18cm{sup 2}, and 9cm or 13.5cm thick solid-water compensators were used to position the tumors at either the beam entrance (BE) or the SOBP. Physical doses of 5Gy were delivered to all tumors on a patient beam line at MD Anderson's Proton Therapy Center. Results: The photoacoustic experiment reveled that our nanoparticles leak from the tumor-feeding vasculature and accumulate within the tumor volume over time. Additionally, TEM images showed gAuNP are internalized in cancer cells, accumulating within the cytoplasm, whereas pAuNP are not. Tumor-growth was delayed by 11 or 32days in mice receiving gAuNP irradiated at the BE or the SOBP, relative to proton radiation alone. Survival curves (ongoing experiment) reveal that gAuNPs improved survival by 36% or 74% for tumors irradiated at the BE or SOBP. Conclusion: These important, albeit preliminary, in vivo findings reveal nanoparticles to be potent sensitizers to proton therapy. Further, conjugation of AuNPs to tumor-specific antigens that promote enhanced cellular internalization improved both tumor-growth delay and survival of mice after proton therapy.« less

Practical Radiobiology for Proton Therapy Planning

NASA Astrophysics Data System (ADS)

Jones, Bleddyn

2017-12-01

Practical Radiobiology for Proton Therapy Planning covers the principles, advantages and potential pitfalls that occur in proton therapy, especially its radiobiological modelling applications. This book is intended to educate, inform and to stimulate further research questions. Additionally, it will help proton therapy centres when designing new treatments or when unintended errors or delays occur. The clear descriptions of useful equations for high LET particle beam applications, worked examples of many important clinical situations, and discussion of how proton therapy may be optimized are all important features of the text. This important book blends the relevant physics, biology and medical aspects of this multidisciplinary subject. Part of Series in Physics and Engineering in Medicine and Biology.

Delayed posthypoxic demyelination. Association with arylsulfatase A deficiency and lactic acidosis on proton MR spectroscopy.

PubMed

Gottfried, J A; Mayer, S A; Shungu, D C; Chang, Y; Duyn, J H

1997-11-01

Delayed demyelination is a rare and poorly understood complication of hypoxic brain injury. A previous case report has suggested an association with mild-to-moderate deficiency of arylsulfatase A. We describe a 36-year-old man who recovered completely from an episode of hypoxia related to drug overdose, and 2 weeks later progressed from a confusional state to deep coma. MRI showed diffuse white matter signal changes, and brain biopsy demonstrated a noninflammatory demyelinating process. Proton magnetic resonance spectroscopy revealed elevated choline and lactate and reduced N-acetyl aspartate signal in the affected white matter, consistent with demyelination and a shift to anaerobic metabolism. Arylsulfatase A activity from peripheral leukocytes was approximately 50% of normal, consistent with a "pseudodeficiency" phenotype. These findings confirm the hypothesis that relative arylsulfatase A deficiency predisposes susceptible individuals to delayed posthypoxic leukoencephalopathy and implicates lactic acidosis in the pathogenesis of this disorder.

Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Corrigan, Neva M.; Shaw, Dennis. W. W.; Richards, Todd L.; Estes, Annette M.; Friedman, Seth D.; Petropoulos, Helen; Artru, Alan A.; Dager, Stephen R.

2012-01-01

Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ([superscript 1]HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally…

Remote acute demyelination after focal proton radiation therapy for optic nerve meningioma.

PubMed

Redjal, Navid; Agarwalla, Pankaj K; Dietrich, Jorg; Dinevski, Nikolaj; Stemmer-Rachamimov, Anat; Nahed, Brian V; Loeffler, Jay S

2015-08-01

We present a unique patient with delayed onset, acute demyelination that occurred distant to the effective field of radiation after proton beam radiotherapy for an optic nerve sheath meningioma. The use of stereotactic radiotherapy as an effective treatment modality for some brain tumors is increasing, given technological advances which allow for improved targeting precision. Proton beam radiotherapy improves the precision further by reducing unnecessary radiation to surrounding tissues. A 42-year-old woman was diagnosed with an optic nerve sheath meningioma after initially presenting with vision loss. After biopsy of the lesion to establish diagnosis, the patient underwent stereotactic proton beam radiotherapy to a small area localized to the tumor. Subsequently, the patient developed a large enhancing mass-like lesion with edema in a region outside of the effective radiation field in the ipsilateral frontal lobe. Given imaging features suggestive of possible primary malignant brain tumor, biopsy of this new lesion was performed and revealed an acute demyelinating process. This patient illustrates the importance of considering delayed onset acute demyelination in the differential diagnosis of enhancing lesions in patients previously treated with radiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Contrasting phagosome pH regulation and maturation in human M1 and M2 macrophages

PubMed Central

Canton, Johnathan; Khezri, Rojyar; Glogauer, Michael; Grinstein, Sergio

2014-01-01

Macrophages respond to changes in environmental stimuli by assuming distinct functional phenotypes, a phenomenon referred to as macrophage polarization. We generated classically (M1) and alternatively (M2) polarized macrophages—two extremes of the polarization spectrum—to compare the properties of their phagosomes. Specifically, we analyzed the regulation of the luminal pH after particle engulfment. The phagosomes of M1 macrophages had a similar buffering power and proton (equivalent) leakage permeability but significantly reduced proton-pumping activity compared with M2 phagosomes. As a result, only the latter underwent a rapid and profound acidification. By contrast, M1 phagosomes displayed alkaline pH oscillations, which were caused by proton consumption upon dismutation of superoxide, followed by activation of a voltage- and Zn2+-sensitive permeation pathway, likely HV1 channels. The paucity of V-ATPases in M1 phagosomes was associated with, and likely caused by, delayed fusion with late endosomes and lysosomes. The delayed kinetics of maturation was, in turn, promoted by the failure of M1 phagosomes to acidify. Thus, in M1 cells, elimination of pathogens through deployment of the microbicidal NADPH oxidase is given priority at the expense of delayed acidification. By contrast, M2 phagosomes proceed to acidify immediately in order to clear apoptotic bodies rapidly and effectively. PMID:25165138

The Beta-Delayed Proton and Gamma Decay of 27P for Nuclear Astrophysics

NASA Astrophysics Data System (ADS)

McCleskey, E.; Banu, A.; McCleskey, M.; Roeder, B.; Saastamoinen, A.; Spiridon, A.; Trache, L.; Tribble, R. E.; Davinson, T.; Doherty, D.; Lotay, G. J.; Wallace, J.; Woods, P. J.

2013-10-01

The main creation site of 26Al is currently under debate. The reactions for its creation or destruction are also not completely known. When 26Al is created in novae, the reaction chain is: 24Mg(p,γ)25Al(β + v)25Mg(p,γ)26Al, but this chain can be by-passed by another chain: 25Al(p,γ)26Si(p,γ)27P and it can also be destroyed directly. Another way to by-pass it is through 26mAl(p,γ)27Si* which is dominated by resonant capture. Using the Momentum Achromat Recoil Spectrometer (MARS) at the Texas A&M Cyclotron Institute and inverse kinematics, this destruction reaction was studied by the beta-delayed proton and gamma decay of 27P. Due to selection rules, states populated above the proton threshold in the compound system (27Si*) can decay to 26mAl, which are the states of interest for the capture reaction. James Madison University, VA, USA.

β decays of the heaviest N =Z -1 nuclei and proton instability of 97In

NASA Astrophysics Data System (ADS)

Park, J.; Krücken, R.; Lubos, D.; Gernhäuser, R.; Lewitowicz, M.; Nishimura, S.; Ahn, D. S.; Baba, H.; Blank, B.; Blazhev, A.; Boutachkov, P.; Browne, F.; Čeliković, I.; de France, G.; Doornenbal, P.; Faestermann, T.; Fang, Y.; Fukuda, N.; Giovinazzo, J.; Goel, N.; Górska, M.; Grawe, H.; Ilieva, S.; Inabe, N.; Isobe, T.; Jungclaus, A.; Kameda, D.; Kim, G. D.; Kim, Y.-K.; Kojouharov, I.; Kubo, T.; Kurz, N.; Lorusso, G.; Moschner, K.; Murai, D.; Nishizuka, I.; Patel, Z.; Rajabali, M. M.; Rice, S.; Sakurai, H.; Schaffner, H.; Shimizu, Y.; Sinclair, L.; Söderström, P.-A.; Steiger, K.; Sumikama, T.; Suzuki, H.; Takeda, H.; Wang, Z.; Watanabe, H.; Wu, J.; Xu, Z. Y.

2018-05-01

We report on new or more precise half-lives, β -decay endpoint energies, and β -delayed proton emission branching ratios of 91Pd, 95Cd, 97In, and 99Sn. The measured values are consistent with known mirror transitions in lighter Tz=-1 /2 nuclei, shell-model calculations, and various mass models. In addition to the β -decaying (9 /2+) ground state, circumstantial evidence for a short-lived, proton-emitting isomer with spin (1 /2-) was found in 97In. Based on the experimental data, a semiempirical theory on proton emission, and shell-model calculations, the proton separation energy of the 97In ground state was determined to be -0.10 ±0.19 MeV. The existence of the short-lived, proton-unstable (1 /2-) isomer in 97In establishes 96Cd as an r p -process waiting point.

Detailed Analysis of Apoptosis and Delayed Luminescence of Human Leukemia Jurkat T Cells after Proton Irradiation and Treatments with Oxidant Agents and Flavonoids

PubMed Central

Baran, Irina; Ganea, Constanta; Privitera, Simona; Scordino, Agata; Barresi, Vincenza; Musumeci, Francesco; Mocanu, Maria Magdalena; Condorelli, Daniele F.; Ursu, Ioan; Grasso, Rosaria; Gulino, Marisa; Garaiman, Alexandru; Musso, Nicolò; Cirrone, Giuseppe A. Pablo; Cuttone, Giacomo

2012-01-01

Following previous work, we investigated in more detail the relationship between apoptosis and delayed luminescence (DL) in human leukemia Jurkat T cells under a wide variety of treatments. We used menadione and hydrogen peroxide to induce oxidative stress and two flavonoids, quercetin, and epigallocatechin gallate, applied alone or in combination with menadione or H2O2. 62 MeV proton beams were used to irradiate cells under a uniform dose of 2 or 10 Gy, respectively. We assessed apoptosis, cell cycle distributions, and DL. Menadione, H2O2 and quercetin were potent inducers of apoptosis and DL inhibitors. Quercetin decreased clonogenic survival and the NAD(P)H level in a dose-dependent manner. Proton irradiation with 2 Gy but not 10 Gy increased the apoptotic rate. However, both doses induced a substantial G2/M arrest. Quercetin reduced apoptosis and prolonged the G2/M arrest induced by radiation. DL spectroscopy indicated that proton irradiation disrupted the electron flow within Complex I of the mitochondrial respiratory chain, thus explaining the massive necrosis induced by 10 Gy of protons and also suggested an equivalent action of menadione and quercetin at the level of the Fe/S center N2, which may be mediated by their binding to a common site within Complex I, probably the rotenone-binding site. PMID:22829956

High Dose Proton Pump Inhibitor Infusion Versus Bolus Injection for the Prevention of Bleeding After Endoscopic Submucosal Dissection: Prospective Randomized Controlled Study.

PubMed

Choi, Cheol Woong; Kang, Dae Hwan; Kim, Hyung Wook; Hong, Joung Boom; Park, Su Bum; Kim, Su Jin; Cho, Mong

2015-07-01

A high dose of continuous intravenous infusion of proton pump inhibitor (PPI) is the standard treatment for peptic ulcer bleeding. The optimal dose for the prevention of bleeding after endoscopic submucosal dissection (ESD) is unclear. The purpose of this study was to determine whether stronger acid suppression more effectively prevents bleeding and high risk ulcer stigma (HRS) after gastric ESD. A total of 273 patients who underwent ESD were randomly assigned to one of two treatment groups: the continuous infusion group and the bolus injection group. Second-look endoscopy was performed on the following day after ESD. The incidences and risk factors of HRS identified by second-look endoscopy and delayed bleeding were analyzed. There were no differences in the incidences of HRS and delayed bleeding between two treatment groups. The incidence of HRS was 15.8 % (43/273) and the gross morphology (flat or depressed) was identified as a significant factor associated with HRS. The incidence of delayed bleeding was 8.4 % (23/273) and the gross morphology (flat) and the presence of submucosal invasive cancer were identified as the associated risk factors for delayed bleeding. The incidences of delayed bleeding and HRS identified by second-look endoscopy were not affected by PPI infusion methods. Flat or depressed morphologic lesions and submucosal invasive cancer should be closely monitored.

Proton irradiation and endometriosis

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

Wood, D.H.; Yochmowitz, M.G.; Salmon, Y.L.

1983-08-01

It was found that female rhesus monkeys given single total-body exposures of protons of varying energies developed endometriosis at a frequency significantly higher than that of nonirradiated animals of the same age. The minimum latency period was determined to be 7 years after the proton exposure. The doses and energies of the radiation received by the experimental animals were within the range that could be received by an aircrew member in near-earth orbit during a random solar flare event. It is concluded that endometriosis should be a consideration in assessing the risk of delayed radiation effects in female crew members.more » 15 references.« less

Analysis of Muon Induced Neutrons in Detecting High Z Nuclear Materials

DTIC Science & Technology

2015-03-01

mass distributions, delayed fission probabilities, and prompt to delayed fission ratios [16]. 10 2.3 Muon Catalyzed Fusion Fusion occurs when two light ...proton number; A is the atomic mass; ⇢ is the material density; = v/c where v is the velocity of the particle and c is the speed of light ; is the...8217) %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% 81 % Combine all neutron events time stamps into one vector %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% timeindex of

Searches for dark matter and new physics with unconventional signatures

NASA Astrophysics Data System (ADS)

Wulz, C.-E.; CMS Collaboration

2017-07-01

Selected results on searches for dark matter and unconventional signatures with the CMS detector are presented. Dark matter searches in channels with one or two jets, single photons, vector bosons, or top and bottom quarks combined with missing momentum in the final states are described. Unusual signatures such as displaced objects, disappearing or kinked tracks, delayed or stopped particles have also been explored. The analyses were performed with proton-proton data recorded at LHC centre-of-mass energies up to 13TeV.

Proton irradiation and endometriosis

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

Wood, D.H.; Yochmowitz, M.G.; Salmon, Y.L.

1983-08-01

Female rhesus monkeys given single total-body exposures of protons of varying energies developed endometriosis at a frequency significantly higher than that of nonirradiated animals of the same age. The minimum latency period was 7 years after exposure. The doses and energies of the radiation received were within the range that could be received by an aircrew member in near-earth orbit during a random solar flare event, leading to the conclusion that endometriosis should be a consideration in assessing the risk of delayed radiation effects in female crewmembers.

Decay property of sup 20 Na for the onset mechanism of the rapid-proton process

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

Kubono, S.; Ikeda, N.; Funatsu, Y.

1992-07-01

The decay property of {sup 20}Na was studied using a {sup 20}Mg beam to learn better the onset mechanism of the rapid-proton process. The delayed protons were successfully measured, which correspond to one of the possible 1{sup +} states in {sup 20}Na. There is no clear beta decay to the first excited 1{sup +} state above the proton threshold, suggesting that this state would not be the {ital s}-wave resonance in the thermal reaction of {sup 19}Ne+{ital p} as was expected before. The half-life time of {sup 20}Mg is determined to be 114{plus minus}17 ms. The stellar reaction rate ofmore » {sup 19}Ne({ital p},{gamma}){sup 20}Na is also discussed based on the present experimental result.« less

Possibilities of the forecast of generation of the high energy solar protons for the safety of Mars mission

NASA Astrophysics Data System (ADS)

Avakyan, S. V.; Gaponov, V. A.; Nicol'skii, G. A.; Solov'ev, A. A.

2017-06-01

During interplanetary flight, after large solar flares, astronauts are subject to the impact of relativistic solar protons. These particles produce an especially strong effect during extravehicular activity or landing on Mars (in the future). The relativistic protons reach the orbits of the Earth and Mars with a delay of several hours relative to solar X-rays and UV radiation. In this paper, we discuss a new opportunity to predict the most dangerous events caused by Solar Cosmic Rays with protons of maximum (relativistic) energy, known in the of solar-terrestrial physics asGround Level Enhancements or Ground Level Events (GLEs). This new capability is based on a close relationship between the dangerous events and decrease ofTotal Solar Irradiance (TSI)which precedes these events. This important relationship is revealed for the first time.

Selective excitation enables assignment of proton resonances and (1)H-(1)H distance measurement in ultrafast magic angle spinning solid state NMR spectroscopy.

PubMed

Zhang, Rongchun; Ramamoorthy, Ayyalusamy

2015-07-21

Remarkable developments in ultrafast magic angle spinning (MAS) solid-state NMR spectroscopy enabled proton-based high-resolution multidimensional experiments on solids. To fully utilize the benefits rendered by proton-based ultrafast MAS experiments, assignment of (1)H resonances becomes absolutely necessary. Herein, we propose an approach to identify different proton peaks by using dipolar-coupled heteronuclei such as (13)C or (15)N. In this method, after the initial preparation of proton magnetization and cross-polarization to (13)C nuclei, transverse magnetization of desired (13)C nuclei is selectively prepared by using DANTE (Delays Alternating with Nutations for Tailored Excitation) sequence and then, it is transferred to bonded protons with a short-contact-time cross polarization. Our experimental results demonstrate that protons bonded to specific (13)C atoms can be identified and overlapping proton peaks can also be assigned. In contrast to the regular 2D HETCOR experiment, only a few 1D experiments are required for the complete assignment of peaks in the proton spectrum. Furthermore, the finite-pulse radio frequency driven recoupling sequence could be incorporated right after the selection of specific proton signals to monitor the intensity buildup for other proton signals. This enables the extraction of (1)H-(1)H distances between different pairs of protons. Therefore, we believe that the proposed method will greatly aid in fast assignment of peaks in proton spectra and will be useful in the development of proton-based multi-dimensional solid-state NMR experiments to study atomic-level resolution structure and dynamics of solids.

Water at hydrophobic interfaces delays proton surface-to-bulk transfer and provides a pathway for lateral proton diffusion

PubMed Central

Zhang, Chao; Knyazev, Denis G.; Vereshaga, Yana A.; Ippoliti, Emiliano; Nguyen, Trung Hai; Carloni, Paolo; Pohl, Peter

2012-01-01

Fast lateral proton migration along membranes is of vital importance for cellular energy homeostasis and various proton-coupled transport processes. It can only occur if attractive forces keep the proton at the interface. How to reconcile this high affinity to the membrane surface with high proton mobility is unclear. Here, we tested whether a minimalistic model interface between an apolar hydrophobic phase (n-decane) and an aqueous phase mimics the biological pathway for lateral proton migration. The observed diffusion span, on the order of tens of micrometers, and the high proton mobility were both similar to the values previously reported for lipid bilayers. Extensive ab initio simulations on the same water/n-decane interface reproduced the experimentally derived free energy barrier for the excess proton. The free energy profile GH+ adopts the shape of a well at the interface, having a width of two water molecules and a depth of 6 ± 2RT. The hydroniums in direct contact with n-decane have a reduced mobility. However, the hydroniums in the second layer of water molecules are mobile. Their in silico diffusion coefficient matches that derived from our in vitro experiments, (5.7 ± 0.7) × 10-5 cm2 s-1. Conceivably, these are the protons that allow for fast diffusion along biological membranes. PMID:22675120

Highly Efficient Thermally Activated Delayed Fluorescence from an Excited-State Intramolecular Proton Transfer System

PubMed Central

2017-01-01

Thermally activated delayed fluorescence (TADF) materials have shown great potential for highly efficient organic light-emitting diodes (OLEDs). While the current molecular design of TADF materials primarily focuses on combining donor and acceptor units, we present a novel system based on the use of excited-state intramolecular proton transfer (ESIPT) to achieve efficient TADF without relying on the well-established donor–acceptor scheme. In an appropriately designed acridone-based compound with intramolecular hydrogen bonding, ESIPT leads to separation of the highest occupied and lowest unoccupied molecular orbitals, resulting in TADF emission with a photoluminescence quantum yield of nearly 60%. High external electroluminescence quantum efficiencies of up to 14% in OLEDs using this emitter prove that efficient triplet harvesting is possible with ESIPT-based TADF materials. This work will expand and accelerate the development of a wide variety of TADF materials for high performance OLEDs. PMID:28776019

First identification of excited states in Ba 117 using the recoil- β -delayed proton tagging technique

DOE PAGES

Ding, B.; Liu, Z.; Seweryniak, D.; ...

2017-02-01

Excited states have been observed for the first time in the neutron-deficient nucleus 117Ba using the recoil-decay tagging technique following the heavy-ion fusion-evaporation reaction 64Zn( 58Ni, 2p3n) 117Ba. Prompt γ rays have been assigned to 117Ba through correlations with β-delayed protons following the decay of A = 117 recoils. Through the analysis of the γ–γ coincidence relationships, a high-spin level scheme consisting of two bands has been established in 117Ba. Based on the systematics of the level spacings in the neighboring barium isotopes, the two bands are proposed to have νh 11/2[532]5/2 – and νd 5/2[413]5/2 + configurations, respectively. Lastly,more » the observed band-crossing properties are interpreted in the framework of cranked shell model.« less

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

Davies, Paul John; Grawe, H.; Moschner, K.

The first evidence for β -delayed proton emission from the 16 + spin gap isomer in 96Cd is presented. The data were obtained from the Rare Isotope Beam Factory, at the RIKEN Nishina Center, using the BigRIPS spectrometer and the EURICA decay station. βp branching ratios for the ground state and 16 + isomer have been extracted along with more precise lifetimes for these states and the lifetime for the ground state decay of 95Cd. Large scale shell model (LSSM) calculations have been performed and WKB estimates made for ℓ=0,2,4 proton emission from three resonance-like states in 96Ag, that aremore » populated by the β decay of the isomer, and the results compared to the new data. The calculations suggest that ℓ=2 proton emission from the resonance states, which reside ~5 MeV above the proton separation energy, dominates the proton decay. Finally, the results highlight the importance of core-excited wavefunction components for the 16 + state.« less

Standard and double-dose intravenous proton pump inhibitor injections for prevention of bleeding after endoscopic resection.

PubMed

Jung, Sung Woo; Kim, Seung Young; Choe, Jung Wan; Hyun, Jong Jin; Jung, Young Kul; Koo, Ja Seol; Yim, Hyung Joon; Lee, Sang Woo

2017-04-01

Endoscopic resection is commonly used to remove gastric neoplasms. However, effective dosing or scheduling of proton pump inhibitors for the prevention of delayed bleeding after endoscopic resection remains unclear. One hundred sixty-six patients with gastric adenoma or early gastric cancer were enrolled. After an endoscopic procedure, each subject was randomly assigned to 40 mg every 24 h (standard dose group) or 40 mg every 12 h (double-dose group) of intravenous pantoprazole for 48 h. Second-look endoscopy was performed on day 2 after endoscopic resection to compare signs of rebleeding and ulcer status between the two groups. Eighty-one patients of the standard dose group and 81 of the double-dose group were analyzed. There were no significant differences in the incidence of delayed bleeding events (1.3% vs 6.2%, P = 0.21) and bleeding ulcer at the second-look endoscopy (6.2% vs 3.9%, P = 0.69) between standard and double-dose groups. There were no other significant variables associated with delayed bleeding or bleeding ulcer on second-look endoscopy. Intravenous pantoprazole 40 mg every 24 h or 12 h for 2 days after endoscopic resection was equally effective for the prevention of delayed bleeding. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

β -delayed γ decay of P 26 : Possible evidence of a proton halo

DOE PAGES

Pérez-Loureiro, D.; Wrede, C.; Bennett, M. B.; ...

2016-06-01

Background: Measurements of β decay provide important nuclear structure information that can be used to probe isospin asymmetries and inform nuclear astrophysics studies. Purpose: To measure the β-delayed γ decay of 26P and compare the results with previous experimental results and shell-model calculations. Method: A 26P fast beam produced using nuclear fragmentation was implanted into a planar germanium detector. Its β-delayed γ-ray emission was measured with an array of 16 high-purity germanium detectors. Positrons emitted in the decay were detected in coincidence to reduce the background. Results: The absolute intensities of 26P β-delayed γ-rays were determined. A total of sixmore » new β-decay branches and 15 new γ-ray lines have been observed for the first time in 26P β-decay. A complete β-decay scheme was built for the allowed transitions to bound excited states of 26Si. ft values and Gamow-Teller strengths were also determined for these transitions and compared with shell model calculations and the mirror β-decay of 26Na, revealing significant mirror asymmetries. Conclusions: A very good agreement with theoretical predictions based on the USDB shell model is observed. The significant mirror asymmetry observed for the transition to the first excited state (δ=51(10)%) may be evidence for a proton halo in 26P.« less

Search for Long-Lived Neutral Particles in Final States with Delayed Photon and Missing Transverse Energy from Proton-Proton Collisions Using the CMS detector

NASA Astrophysics Data System (ADS)

Tambe Ebai, Norbert

We perform a search for long-lived neutral particles in final state with delayed photons and large missing transverse energy produced in LHC proton-proton collisions at center-of-mass energy, √s = 8 TeV. Capitalizing on the excellent timing resolution of the CMS Electromagnetic Calorimeter the search uses photon time measurements made by the Electromagnetic Calorimeter as the main search quantity. We found a single event consistent with our background expectations from the Standard Model and set a model-independent upper limit of 4.37 on number of signal events. We also interpret our results in the context of the SPS8 benchmark GMSB model and show that neutralinos with mean lifetime, tau PSneutralinoOne ≤ 45 ns, and mass, mPSneutralinoOne ≤ 300 GeV/c2, or effective Supersymmetry breaking energy scale, Lambda ≤ 220TeV, are ruled out of existence at 95% CLS confidence level. The exclusion limit on the product of the production cross-section and branching ratio of the neutralino to photon and gravitino decay channel, sigma(PSneutralinoOne → gamma + G˜) x BR, for different lifetimes and masses is derived. Our results confirm for the first time that the CMS Electromagnetic Calorimeter provides good sensitivity to search for long-lived neutral particles with lifetimes up to 40 ns and masses up to 300 GeV/c2 using only timing measurements.

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.

Proton-decay spectroscopic studies of the exotic nuclides aluminum-23, silicon-23, aluminum-22 and rubidium-77

NASA Astrophysics Data System (ADS)

Rowe, Michael William

Aluminum-23 was produced by 40 MeV 3He2+ bombardments of Mg targets in four experiments at the LBNL 88' ' Cyclotron. Reaction products were transported via helium-jet to a detection chamber where they were counted using two low-energy particle-identification (PI) telescopes. New proton groups were observed with laboratory energies (and intensities relative to the known peak at 838 +/- 5 keV) of 246 20 (33 +/- 3%) and 556 +/- 5 keV (68 +/- 5%), respectively. Several possible decay assignments are discussed for the former group. The possibility that it originates from the decay through the isobaric analog state (IAS) and corresponding implications for isospin mixing and the proton-capture resonance strength are discussed. The Gamow-Teller strength function has been deduced from these and several weaker proton transitions; the results are compared with theoretical predictions. Silicon-23 and 22Al were produced in a 110 MeV 3He2+ bombardment of a 24Mg target; reaction products were transported via helium jet and observed by two PI telescopes with proton sensitivity from 0-35-12.5 MeV. Three weak proton peaks at 7673 +/- 33, 9642 +/- 57 and 10861 +/- 68 keV have been tentatively assigned to the beta-delayed proton decay of 23Si through its IAS. From these results, the estimated 23Si mass excess is 23.25 +/- 0.05 MeV. Beta-delayed two-proton sum peaks were observed at 4478 +/- 15 and 6111 +/- 15 keV (c.m.), in agreement with earlier work an the decay of 22Al at wide relative-emission angles. The energies of several weaker two-proton sum peaks were compared with predicted and experimental values for the β-2p decay of 23Si. A search for proton emission from a predicted 19/2- isomer of 77Rb has been performed in three bombardments of Ca targets by 40Ca beams at energies of 145,160 and 132 MeV. Products of the first two bombardments were transported via helium jet and observed by two PI telescopes. In the third bombardment, the mass separator RAMA transported mass-77 products to a PI telescope and two gamma-ray detectors. The direct and mass-separated measurements set limits of ~5 × 10-6 and 1 × 10- 5, respectively, an production of the isomer relative to the ground state, assuming an isomer half- life of 240 ms or longer.

Proton-decay spectroscopic studies of the exotic nuclides aluminum-23, silicon-23, aluminum-22 and rubidium-77

NASA Astrophysics Data System (ADS)

Rowe, Michael William

1998-09-01

Aluminum-23 was produced by 40 MeV 3He2+ bombardments of Mg targets in four experiments at the LBNL 88' ' Cyclotron. Reaction products were transported via helium-jet to a detection chamber where they were counted using two low-energy particle-identification (PI) telescopes. New proton groups were observed with laboratory energies (and intensities relative to the known peak at 838 +/- 5 keV) of 246 20 (33 +/- 3%) and 556 +/- 5 keV (68 +/- 5%), respectively. Several possible decay assignments are discussed for the former group. The possibility that it originates from the decay through the isobaric analog state (IAS) and corresponding implications for isospin mixing and the proton-capture resonance strength are discussed. The Gamow-Teller strength function has been deduced from these and several weaker proton transitions; the results are compared with theoretical predictions. Silicon-23 and 22Al were produced in a 110 MeV 3He2+ bombardment of a 24Mg target; reaction products were transported via helium jet and observed by two PI telescopes with proton sensitivity from 0-35-12.5 MeV. Three weak proton peaks at 7673 +/- 33, 9642 +/- 57 and 10861 +/- 68 keV have been tentatively assigned to the beta-delayed proton decay of 23Si through its IAS. From these results, the estimated 23Si mass excess is 23.25 +/- 0.05 MeV. Beta-delayed two-proton sum peaks were observed at 4478 +/- 15 and 6111 +/- 15 keV (c.m.), in agreement with earlier work an the decay of 22Al at wide relative-emission angles. The energies of several weaker two-proton sum peaks were compared with predicted and experimental values for the β-2p decay of 23Si. A search for proton emission from a predicted 19/2- isomer of 77Rb has been performed in three bombardments of Ca targets by 40Ca beams at energies of 145,160 and 132 MeV. Products of the first two bombardments were transported via helium jet and observed by two PI telescopes. In the third bombardment, the mass separator RAMA transported mass-77 products to a PI telescope and two gamma-ray detectors. The direct and mass-separated measurements set limits of ~5 × 10-6 and 1 × 10- 5, respectively, an production of the isomer relative to the ground state, assuming an isomer half- life of 240 ms or longer.

[Comparison on Oral versus Intravenous Proton Pump Inhibitors for Prevention of Bleeding after Endoscopic Submucosal Dissection of Gastric Lesions].

PubMed

Jung, Yeoun Su; Kim, Kyeong Ok; Lee, Si Hyung; Jang, Byung Ik; Kim, Tae Nyeun

2016-02-01

Although intravenous proton pump inhibitor (PPI) has been used for the prevention of post endoscopic submucosal dissection (ESD) bleeding, the route of administration has not been confirmed. The aim of the present study was to compare the efficacy of intravenous and oral PPI administration for the prevention of delayed post ESD bleeding. Total 166 consecutive patients were randomly assigned to 30 mg lansoprazol twice a day (PO group) and 120 mg pantoprazole intravenous injection (IV group) for 48 hours. Finally, 65 patients in PO group and 87 patients in IV group were analyzed. After ESD, all patients underwent follow up endoscopy after 24 hours and were observed the symptoms of bleeding up to 60 days after ESD. Age, sex and use of anticoagulants were not different between groups. At follow up endoscopy after 24 hours, oozing and exposed vessel was noted in 4.6% of PO group and 8.0% of IV group and there was no significant difference. Delayed bleeding occurred in 4 of 65 patients (6.2%) in the PO group and 8 of 87 patients (9.2%) in the IV group (p>0.999). By multivariate analysis, oozing or exposed vessels at follow up endoscopy were risk factors for delayed bleeding (OR=17.5, p=0.022). There was no significant difference in the delayed bleeding, length of hospital stay according to the administration route. Bleeding stigmata at follow up endoscopy was risk factor of delayed bleeding. Oral PPI administration can cost-effectively replace IV PPI for prevention of post ESD bleeding.

Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies.

PubMed

Missaghi, Shahrzad; Young, Cara; Fegely, Kurt; Rajabi-Siahboomi, Ali R

2010-02-01

Formulation of proton pump inhibitors (PPIs) into oral solid dosage forms is challenging because the drug molecules are acid-labile. The aim of this study is to evaluate different formulation strategies (monolithic and multiparticulates) for three PPI drugs, that is, rabeprazole sodium, lansoprazole, and esomeprazole magnesium, using delayed release film coating applications. The core tablets of rabeprazole sodium were prepared using organic wet granulation method. Multiparticulates of lansoprazole and esomeprazole magnesium were prepared through drug layering of sugar spheres, using powder layering and suspension layering methods, respectively. Tablets and drug-layered multiparticulates were seal-coated, followed by delayed release film coating application, using Acryl-EZE(R), aqueous acrylic enteric system. Multiparticulates were then filled into capsules. The final dosage forms were evaluated for physical properties, as well as in vitro dissolution testing in both compendial acid phase, 0.1N HCl (pH 1.2), and intermediate pH, acetate buffer (pH 4.5), followed by phosphate buffer, pH 6.8. The stability of the delayed release dosage forms was evaluated upon storage in accelerated conditions [40 degrees C/75% relative humidity] for 3 months. All dosage forms demonstrated excellent enteric protection in the acid phase, followed by rapid release in their respective buffer media. Moreover, the delayed release dosage forms remained stable under accelerated stability conditions for 3 months. Results showed that Acryl-EZE enteric coating systems provide excellent performance in both media (0.1N HCl and acetate buffer pH 4.5) for monolithic and multiparticulate dosage forms.

Flame detector operable in presence of proton radiation

NASA Technical Reports Server (NTRS)

Walker, D. J.; Turnage, J. E.; Linford, R. M. F.; Cornish, S. D. (Inventor)

1974-01-01

A detector of ultraviolet radiation for operation in a space vehicle which orbits through high intensity radiation areas is described. Two identical ultraviolet sensor tubes are mounted within a shield which limits to acceptable levels the amount of proton radiation reaching the sensor tubes. The shield has an opening which permits ultraviolet radiation to reach one of the sensing tubes. The shield keeps ultraviolet radiation from reaching the other sensor tube, designated the reference tube. The circuitry of the detector subtracts the output of the reference tube from the output of the sensing tube, and any portion of the output of the sensing tube which is due to proton radiation is offset by the output of the reference tube. A delay circuit in the detector prevents false alarms by keeping statistical variations in the proton radiation sensed by the two sensor tubes from developing an output signal.

Selective excitation enables assignment of proton resonances and {sup 1}H-{sup 1}H distance measurement in ultrafast magic angle spinning solid state NMR spectroscopy

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

Zhang, Rongchun; Ramamoorthy, Ayyalusamy, E-mail: ramamoor@umich.edu

2015-07-21

Remarkable developments in ultrafast magic angle spinning (MAS) solid-state NMR spectroscopy enabled proton-based high-resolution multidimensional experiments on solids. To fully utilize the benefits rendered by proton-based ultrafast MAS experiments, assignment of {sup 1}H resonances becomes absolutely necessary. Herein, we propose an approach to identify different proton peaks by using dipolar-coupled heteronuclei such as {sup 13}C or {sup 15}N. In this method, after the initial preparation of proton magnetization and cross-polarization to {sup 13}C nuclei, transverse magnetization of desired {sup 13}C nuclei is selectively prepared by using DANTE (Delays Alternating with Nutations for Tailored Excitation) sequence and then, it is transferredmore » to bonded protons with a short-contact-time cross polarization. Our experimental results demonstrate that protons bonded to specific {sup 13}C atoms can be identified and overlapping proton peaks can also be assigned. In contrast to the regular 2D HETCOR experiment, only a few 1D experiments are required for the complete assignment of peaks in the proton spectrum. Furthermore, the finite-pulse radio frequency driven recoupling sequence could be incorporated right after the selection of specific proton signals to monitor the intensity buildup for other proton signals. This enables the extraction of {sup 1}H-{sup 1}H distances between different pairs of protons. Therefore, we believe that the proposed method will greatly aid in fast assignment of peaks in proton spectra and will be useful in the development of proton-based multi-dimensional solid-state NMR experiments to study atomic-level resolution structure and dynamics of solids.« less

Photonuclear Contributions to SNS Pulse Shapes

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

McClanahan, Tucker C.; Iverson, Erik B.; Gallmeier, Franz X.

Short-pulsed sources like the Spallation Neutron Source (SNS) and ISIS produce bursts of neutron pulses at rates of 10-60 Hz, with sub-microsecond proton pulses impacting on high-Z target materials. Moderators are grouped around the target to receive the fast neutrons generated from spallation reactions to moderate them effciently to thermal and sub-thermal energies and to feed narrow neutron pulses to neutron scattering instruments. The scattering instruments use the neutrons as a probe for material investigations, and make use of time-of-flight (TOF) methods for resolving the neutron energy. The energy resolution of scattering instruments depends on the narrow time-structure of themore » neutron pulses, while neutrons in the long tail of the emission time distributions can degrade the instrument performance and add undesired background to measurements. The SNS neutronics team is investigating a possible source term impacting the background at short-pulsed spallation sources. The ISIS TS2 project claims to have significantly reduced neutron scattering instrument background levels by the elimination or reduction of iron shielding in the target-moderator-reflector assembly. An alternative hypothesis, also proposed by ISIS, suggests that this apparent reduction arises from moving beamline shielding away from the neutron guide channels, reducing albedo down the beamlines. In both hypotheses, the background neutrons in question are believed to be generated by photonuclear reactions. If the background neutrons are indeed generated via photonuclear channels, then they are generated in a time-dependent fashion, since most of the high-energy photons capable of inducing photonuclear production are gone within a few microseconds following the proton pulse. To evaluate this e ect, we have enabled photonuclear reactions in a series of studies for the SNS first target station (FTS) taking advantage of its Monte Carlo model. Using a mixture of ENDF/B VII.0 and TENDL-2014 photonuclear cross sections available and the CEM03 physics model within MCNPX 2.6.0 in the simulation, we are able to estimate the impact of photoneutron production on both overall neutron production and delayed neutron production. We find that a significant number of photon-induced neutrons are produced a few milliseconds after the proton pulse, following prompt gamma emission through the capture of neutrons in the slowing-down and thermalization processes. We name these "slowing-down delayed neutrons" to distinguish them from either "activation-delayed neutrons" or "beta-delayed neutrons." The beta-delayed and activation-delayed neutrons were not part of this study, and will be addressed elsewhere. While these other delayed neutron channels result in the time-independent (constant) production of fast neutrons outside of the prompt pulse, the slowing-down delayed neutrons also a ect the shape of the pulses. Although numerically insignificant in most cases, we describe a set of scenarios related to T0-chopper operation in which the slowing-down delayed neutrons may be important.« less

Effects of 100MeV protons delivered at 0.5 or 1cGy/min on the in vivo induction of early and delayed chromosomal damage.

PubMed

Rithidech, Kanokporn Noy; Honikel, Louise M; Reungpatthanaphong, Paiboon; Tungjai, Montree; Golightly, Marc; Whorton, Elbert B

2013-08-30

Little is known about in vivo cytogenetic effects of protons delivered at the dose and dose rates encountered in space. We determined the effects of 100MeV protons, one of the most abundant type of protons produced during solar particle events (SPE), on the induction of chromosome aberrations (CAs) in bone marrow (BM) cells collected at early (3 and 24h) and late (6 months) time-points from groups of BALB/cJ mice (a known radiosensitive strain) exposed whole-body to 0 (sham-controls), 0.5, or 1.0Gy of 100MeV protons, delivered at 0.5 or 1.0cGy/min. These doses and dose-rates are comparable to those produced during SPE events. Additionally, groups of mice were exposed to 0 or 1Gy of (137)Cs γ rays (delivered at 1cGy/min) as a reference radiation. The kinetics of formation/reduction of gamma-histone 2-AX (γH2AX) were determined in BM cells collected at 1.5, 3, and 24h post-irradiation to assess the early-response. There were five mice per treatment-group per harvest-time. Our data indicated that the kinetics of γH2AX formation/reduction differed, depending on the dose and dose rate of protons. Highly significant numbers of abnormal cells and chromatid breaks (p<0.01), related to those in sham-control groups, were detected in BM cells collected at each time-point, regardless of dose or dose-rate. The finding of significant increases in the frequencies of delayed non-clonal and clonal CAs in BM cells collected at a late time-point from exposed mice suggested that 0.5 or 1Gy of 100MeV protons is capable of inducing genomic instability in BM cells. However, the extent of effects induced by these two low dose rates was comparable. Further, the results showed that the in vivo cytogenetic effects induced by 1Gy of 100MeV protons or (137)Cs γ rays (delivered at 1cGy/min) were similar. Copyright © 2013 Elsevier B.V. All rights reserved.

The role of core excitations in the structure and decay of the 16 + spin-gap isomer in 96Cd

DOE PAGES

Davies, Paul John; Grawe, H.; Moschner, K.; ...

2017-02-14

The first evidence for β -delayed proton emission from the 16 + spin gap isomer in 96Cd is presented. The data were obtained from the Rare Isotope Beam Factory, at the RIKEN Nishina Center, using the BigRIPS spectrometer and the EURICA decay station. βp branching ratios for the ground state and 16 + isomer have been extracted along with more precise lifetimes for these states and the lifetime for the ground state decay of 95Cd. Large scale shell model (LSSM) calculations have been performed and WKB estimates made for ℓ=0,2,4 proton emission from three resonance-like states in 96Ag, that aremore » populated by the β decay of the isomer, and the results compared to the new data. The calculations suggest that ℓ=2 proton emission from the resonance states, which reside ~5 MeV above the proton separation energy, dominates the proton decay. Finally, the results highlight the importance of core-excited wavefunction components for the 16 + state.« less

2J, 3J-HMBC: A New Long-Range Heteronuclear Shift Correlation Technique Capable of Differentiating 2JCH from 3JCH Correlations to Protonated Carbons

NASA Astrophysics Data System (ADS)

Krishnamurthy, V. V.; Russell, David J.; Hadden, Chad E.; Martin, Gary E.

2000-09-01

The development of a series of new, accordion-optimized long-range heteronuclear shift correlation techniques has been reported. A further derivative of the constant time variable delay introduced in the IMPEACH-MBC experiment, a STAR (Selectively Tailored Accordion F1 Refocusing) operator is described in the present report. Incorporation of the STAR operator with the capability of user-selected homonuclear modulation scaling as in the CIGAR-HMBC experiment, into a long-range heteronuclear shift correlation pulse sequence, 2J,3J-HMBC, affords for the first time in a proton-detected experiment the means of unequivocally differentiating two-bond (2JCH) from three-bond (3JCH) long-range correlations to protonated carbons.

Multiple lesion track structure model

NASA Technical Reports Server (NTRS)

Wilson, John W.; Cucinotta, Francis A.; Shinn, Judy L.

1992-01-01

A multilesion cell kinetic model is derived, and radiation kinetic coefficients are related to the Katz track structure model. The repair-related coefficients are determined from the delayed plating experiments of Yang et al. for the C3H10T1/2 cell system. The model agrees well with the x ray and heavy ion experiments of Yang et al. for the immediate plating, delaying plating, and fractionated exposure protocols employed by Yang. A study is made of the effects of target fragments in energetic proton exposures and of the repair-deficient target-fragment-induced lesions.

The beta-delayed particle decay of neon-17

NASA Astrophysics Data System (ADS)

Morton, Anthony Colin

2001-10-01

An experiment has been proposed to study the β- delayed proton decay of 17Ne into α- particle-emitting states in 16O below the 12C + α threshold in the hopes of using the information gained to constrain the 12C(α, γ) 16O cross section at stellar energies; several experiments have been carried out using the TISOL facility at TRIUMF in an effort to determine the feasibility of such an approach. 17Ne decays by β-particle emission to excited states in 17F; by studying proton-γ-ray coincidences in the decay of these states, relative branching ratios have been obtained for the β-delayed proton decay of 17Ne to γ-ray-emitting states in 16O. These indicate that the decay of the isobaric analogue state (IAS) at 11.1929 MeV in 17F to the 2 + subthreshold state at 6.917 MeV in 16O is a factor of thirty weaker than that of the IAS to any other γ- emitting state. From measurements of the angular correlations observed in such coincidences, the spins and parities of several excited states in 17F have been determined; it has also been shown that the decay of the IAS to the 1 - subthreshold state at 7.117 MeV in 16O is strongly anisotropic, suggesting that it has a strong l = 2 component. Further decay studies have yielded a comprehensive set of β-delayed particle branching ratios from the decay of 17Ne; from these, fAt values and reduced Gamow-Teller matrix elements have been calculated, and the Fermi decay strength of the IAS has been limited to >=2.96 +/- 0.14 indicating a T = / isospin purity of >=98.7 +/- 4.6% for the IAS. The results obtained suggest that a determination of both the E1 and E2 components of the 12C(α, γ) 16O cross section is not feasible; however, with improved yields of 17Ne, a determination of only the E1 component should be.

Pathways of proton release in the bacteriorhodopsin photocycle

NASA Technical Reports Server (NTRS)

Zimanyi, L.; Varo, G.; Chang, M.; Ni, B.; Needleman, R.; Lanyi, J. K.

1992-01-01

The pH dependencies of the rate constants in the photocycles of recombinant D96N and D115N/D96N bacteriorhodopsins were determined from time-resolved difference spectra between 70 ns and 420 ms after photoexcitation. The results were consistent with the model suggested earlier for proteins containing D96N substitution: BR hv----K----L----M1----M2----BR. Only the M2----M1 back-reaction was pH-dependent: its rate increased with increasing [H+] between pH 5 and 8. We conclude from quantitative analysis of this pH dependency that its reverse, the M1----M2 reaction, is linked to the release of a proton from a group with a pKa = 5.8. This suggests a model for wild-type bacteriorhodopsin in which at pH greater than 5.8 the transported proton is released on the extracellular side from this as yet unknown group and on the 100-microseconds time scale, but at pH less than 5.8, the proton release occurs from another residue and later in the photocycle most likely directly from D85 during the O----BR reaction. We postulate, on the other hand, that proton uptake on the cytoplasmic side will be by D96 and during the N----O reaction regardless of pH. The proton kinetics as measured with indicator dyes confirmed the unique prediction of this model: at pH greater than 6, proton release preceded proton uptake, but at pH less than 6, the release was delayed until after the uptake. The results indicated further that the overall M1----M2 reaction includes a second kinetic step in addition to proton release; this is probably the earlier postulated extracellular-to-cytoplasmic reorientation switch in the proton pump.

Global developmental delay in guanidionacetate methyltransferase deficiency: differences in formal testing and clinical observation.

PubMed

Verbruggen, Krijn T; Knijff, Wilma A; Soorani-Lunsing, Roelineke J; Sijens, Paul E; Verhoeven, Nanda M; Salomons, Gajja S; Goorhuis-Brouwer, Siena M; van Spronsen, Francjan J

2007-09-01

Guanidinoacetate N-methyltransferase (GAMT) deficiency is a defect in the biosynthesis of creatine (Cr). So far, reports have not focused on the description of developmental abilities in this disorder. Here, we present the result of formal testing of developmental abilities in a GAMT-deficient patient. Our patient, a 3-year-old boy with GAMT deficiency, presented clinically with a severe language production delay and nearly normal nonverbal development. Treatment with oral Cr supplementation led to partial restoration of the cerebral Cr concentration and a clinically remarkable acceleration of language production development. In contrast to clinical observation, formal testing showed a rather harmonic developmental delay before therapy and a general improvement, but no specific acceleration of language development after therapy. From our case, we conclude that in GAMT deficiency language delay is not always more prominent than delays in other developmental areas. The discrepancy between the clinical impression and formal testing underscores the importance of applying standardized tests in children with developmental delays. Screening for Cr deficiency by metabolite analysis of body fluids or proton magnetic resonance spectroscopy of the brain deficiency should be considered in any child with global developmental delay/mental retardation lacking clues for an alternative etiology.

Variable Delay Multi-Pulse Train for Fast Chemical Exchange Saturation Transfer and Relayed-Nuclear Overhauser Enhancement MRI

PubMed Central

Xu, Jiadi; Yadav, Nirbhay N.; Bar-Shir, Amnon; Jones, Craig K.; Chan, Kannie W. Y.; Zhang, Jiangyang; Walczak, P.; McMahon, Michael T.; van Zijl, Peter C. M.

2013-01-01

Purpose Chemical exchange saturation transfer (CEST) imaging is a new MRI technology allowing the detection of low concentration endogenous cellular proteins and metabolites indirectly through their exchangeable protons. A new technique, variable delay multi-pulse CEST (VDMP-CEST), is proposed to eliminate the need for recording full Z-spectra and performing asymmetry analysis to obtain CEST contrast. Methods The VDMP-CEST scheme involves acquiring images with two (or more) delays between radiofrequency saturation pulses in pulsed CEST, producing a series of CEST images sensitive to the speed of saturation transfer. Subtracting two images or fitting a time series produces CEST and relayed-nuclear Overhauser enhancement CEST maps without effects of direct water saturation and, when using low radiofrequency power, minimal magnetization transfer contrast interference. Results When applied to several model systems (bovine serum albumin, crosslinked bovine serum albumin, l-glutamic acid) and in vivo on healthy rat brain, VDMP-CEST showed sensitivity to slow to intermediate range magnetization transfer processes (rate < 100–150 Hz), such as amide proton transfer and relayed nuclear Overhauser enhancement-CEST. Images for these contrasts could be acquired in short scan times by using a single radiofrequency frequency. Conclusions VDMP-CEST provides an approach to detect CEST effect by sensitizing saturation experiments to slower exchange processes without interference of direct water saturation and without need to acquire Z-spectra and perform asymmetry analysis. PMID:23813483

On the Relationship Between Scintillation Anisotropy and Crystal Structure in Pure Crystalline Organic Scintillator Materials

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

Schuster, Patricia; Feng, Patrick; Brubaker, Erik

We report the scintillation anisotropy effect for proton recoil events has been investigated in five pure organic crystalline materials: anthracene, trans-stilbene, p-terphenyl, bibenzyl, and diphenylacetylene. These measurements include characterization of the scintillation response for one hemisphere of proton recoil directions in each crystal. In addition to standard measurements of the total light output and pulse shape at each angle, the prompt and delayed light anisotropies are analyzed, allowing for investigation of the singlet and triplet molecular excitation behaviors independently. This work provides new quantitative and qualitative observations that make progress toward understanding the physical mechanisms behind the scintillation anisotropy. Thesemore » measurements show that the relationship between the prompt and delayed light anisotropies is correlated with crystal structure, as it changes between the pi-stacked crystal structure materials (anthracene and p-terphenyl) and the herringbone crystal structure materials (stilbene, bibenzyl, and diphenylacetylene). The observations are consistent with a model in which there are preferred directions of kinetic processes for the molecular excitations. Finally, these processes and the impact of their directional dependencies on the scintillation anisotropy are discussed.« less

On the Relationship Between Scintillation Anisotropy and Crystal Structure in Pure Crystalline Organic Scintillator Materials

DOE PAGES

Schuster, Patricia; Feng, Patrick; Brubaker, Erik

2018-05-03

We report the scintillation anisotropy effect for proton recoil events has been investigated in five pure organic crystalline materials: anthracene, trans-stilbene, p-terphenyl, bibenzyl, and diphenylacetylene. These measurements include characterization of the scintillation response for one hemisphere of proton recoil directions in each crystal. In addition to standard measurements of the total light output and pulse shape at each angle, the prompt and delayed light anisotropies are analyzed, allowing for investigation of the singlet and triplet molecular excitation behaviors independently. This work provides new quantitative and qualitative observations that make progress toward understanding the physical mechanisms behind the scintillation anisotropy. Thesemore » measurements show that the relationship between the prompt and delayed light anisotropies is correlated with crystal structure, as it changes between the pi-stacked crystal structure materials (anthracene and p-terphenyl) and the herringbone crystal structure materials (stilbene, bibenzyl, and diphenylacetylene). The observations are consistent with a model in which there are preferred directions of kinetic processes for the molecular excitations. Finally, these processes and the impact of their directional dependencies on the scintillation anisotropy are discussed.« less

Van Allen Probes Observations of Second Harmonic Poloidal Standing Alfvén Waves

NASA Astrophysics Data System (ADS)

Takahashi, Kazue; Oimatsu, Satoshi; Nosé, Masahito; Min, Kyungguk; Claudepierre, Seth G.; Chan, Anthony; Wygant, John; Kim, Hyomin

2018-01-01

Long-lasting second-harmonic poloidal standing Alfvén waves (P2 waves) were observed by the twin Van Allen Probes (Radiation Belt Storm Probes, or RBSP) spacecraft in the noon sector of the plasmasphere, when the spacecraft were close to the magnetic equator and had a small azimuthal separation. Oscillations of proton fluxes at the wave frequency (˜10 mHz) were also observed in the energy (W) range 50-300 keV. Using the unique RBSP orbital configuration, we determined the phase delay of magnetic field perturbations between the spacecraft with a 2nπ ambiguity. We then used finite gyroradius effects seen in the proton flux oscillations to remove the ambiguity and found that the waves were propagating westward with an azimuthal wave number (m) of ˜-200. The phase of the proton flux oscillations relative to the radial component of the wave magnetic field progresses with W, crossing 0 (northward moving protons) or 180° (southward moving protons) at W ˜ 120 keV. This feature is explained by drift-bounce resonance (mωd ˜ ωb) of ˜120 keV protons with the waves, where ωd and ωb are the proton drift and bounce frequencies. At lower energies, the proton phase space density (FH+) exhibits a bump-on-tail structure with ∂FH+/∂W>0 occurring in the 1-10 keV energy range. This FH+ is unstable and can excite P2 waves through bounce resonance (ω ˜ ωb), where ω is the wave frequency.

Delayed effects of proton irradiation in Macaca Mulatta (22-year summary)

NASA Astrophysics Data System (ADS)

Woods, D. H.; Hardy, K. A.; Cox, A. B.; Salmon, Y. L.; Yochmowitz, M. G.; Cordts, R. E.

1989-05-01

Lifetime observations on a group of rhesus monkeys indicate that life expectancy loss from exposure to protons in the energy range encountered in the Van Allen belts and solar proton events can be correlated with the dose and energy of radiation. The primary cause of life shortening is nonleukemic cancers. Radiation also increased the rise of endometriosis (an abnormal proliferation of the lining of the uterus in females). Other effects associated with radiation exposures are lowered glucose tolerance and increased incidence of cataracts. Calculations of the relative risk of fatal cancers in the irradiated subjects reveal that the total body surface dose required to double the risk of death from cancer over a 20-year post exposure period varies with the linear energy transfer (LET) of the radiation. The ability to determine the integrated dose and LET spectrum in space radiation exposures of humans is, therefore, critical to the assessment of lifetime cancer risk.

On the Origin of Long-duration Solar Gamma-ray Flares and Their Connection with SEPs

NASA Astrophysics Data System (ADS)

Bernstein, V.; Winter, L. M.; Cliver, E. W.; Omodei, N.; Pesce-Rollins, M.

2016-12-01

The mechanism producing long-duration solar gamma-ray events (LDGREs) is unresolved. Such events are characterized by high-energy (>100 MeV) pion-decay emission that can be detected for up to 10 hours after the flare impulsive phase. Candidate processes include: (1) prolonged acceleration/trapping of high-energy (> 300 MeV) protons in flare loops and (2) precipitation of energetic protons to the Sun's surface from the CME-driven coronal shock waves. LDGREs, or events with delayed/prolonged pion-dominated emission, have been detected by the SMM GRS, GRO EGRET, and Fermi LAT. To gain insight on their origin, we examine associated GOES X-ray bursts, LASCO CMEs, Wind Waves low-frequency radio bursts, and GOES high-energy proton events, and compare the properties of these various phenomena with the intensities and durations of the observed LDGREs.

Relative proton and γ widths of astrophysically important states in 30S studied in the β-delayed decay of 31Ar

NASA Astrophysics Data System (ADS)

Koldste, G. T.; Blank, B.; Borge, M. J. G.; Briz, J. A.; Carmona-Gallardo, M.; Fraile, L. M.; Fynbo, H. O. U.; Giovinazzo, J.; Johansen, J. G.; Jokinen, A.; Jonson, B.; Kurturkian-Nieto, T.; Kusk, J. H.; Nilsson, T.; Perea, A.; Pesudo, V.; Picado, E.; Riisager, K.; Saastamoinen, A.; Tengblad, O.; Thomas, J.-C.; Van de Walle, J.

2013-05-01

Resonances just above the proton threshold in 30S affect the 29P(p,γ)30S reaction under astrophysical conditions. The (p,γ)-reaction rate is currently determined indirectly and depends on the properties of the relevant resonances. We present here a method for finding the ratio between the proton and γ partial widths of resonances in 30S. The widths are determined from the β2p- and βpγ-decay of 31Ar, which is produced at the ISOLDE radioactive ion beam facility at the European research organization CERN. Experimental limits on the ratio between the proton and γ partial widths for astrophysical relevant levels in 30S have been found for the first time. A level at 4689.2(24)keV is identified in the γ spectrum, and an upper limit on the Γp/Γγ ratio of 0.26 (95% C.L.) is found. In the two-proton spectrum two levels at 5227(3)keV and 5847(4)keV are identified. These levels were previously seen to γ decay and upper limits on the Γγ/Γp ratio of 0.5 and 9, respectively, (95% C.L.) are found, where the latter differs from previous calculations.

Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy.

PubMed

Di Pietro, C; Piro, S; Tabbì, G; Ragusa, M; Di Pietro, V; Zimmitti, V; Cuda, F; Anello, M; Consoli, U; Salinaro, E T; Caruso, M; Vancheri, C; Crimi, N; Sabini, M G; Cirrone, G A P; Raffaele, L; Privitera, G; Pulvirenti, A; Giugno, R; Ferro, A; Cuttone, G; Lo Nigro, S; Purrello, R; Purrello, F; Purrello, M

2006-01-01

Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.

In Vitro Studies on Space Radiation-Induced Delayed Genetic Responses: Shielding Effects

NASA Technical Reports Server (NTRS)

Kadhim, Munira A.; Green, Lora M.; Gridley, Daila S.; Murray, Deborah K.; Tran, Da Thao; Andres, Melba; Pocock, Debbie; Macdonald, Denise; Goodhead, Dudley T.; Moyers, Michael F.

2003-01-01

Understanding the radiation risks involved in spaceflight is of considerable importance, especially with the long-term occupation of ISS and the planned crewed exploration missions. Several independent causes may contribute to the overall risk to astronauts exposed to the complex space environment, such as exposure to GCR as well as SPES. Protons and high-Z energetic particles comprise the GCR spectrum and may exert considerable biological effects even at low fluence. There are also considerable uncertainties associated with secondary particle effects (e.g. HZE fragments, neutrons etc.). The interaction of protons and high-LET particles with biological materials at all levels of biological organization needs to be investigated fully in order to establish a scientific basis for risk assessment. The results of these types of investigation will foster the development of appropriately directed countermeasures. In this study, we compared the biological responses to proton irradiation presented to the target cells as a monoenergetic beam of particles of complex composition delivered to cells outside or inside a tissue phantom head placed in the United States EVA space suit helmet. Measurements of chromosome aberrations, apoptosis, and the induction of key proteins were made in bone marrow from CBA/CaJ and C57BL/6 mice at early and late times post exposure to radiation at 0, 0.5, 1 and 2 Gy while inside or outside of the helmet. The data showed that proton irradiation induced transmissible chromosomal/genomic instability in haematopoietic stem cells in both strains of mice under both irradiation conditions and especially at low doses. Although differences were noted between the mouse strains in the degree and kinetics of transforming growth factor-beta 1 and tumor necrosis factor-alpha secretion, there were no significant differences observed in the level of the induced instability under either radiation condition, or for both strains of mice. Consequently, when normalized to physical dose, the monoenergetic proton field present inside the helmet-protected phantom produced equivalent biological responses, when compared to unshielded cells, as measured by the induction of delayed genetic effects in murine haematopoietic stem cells.

SU-C-207A-04: Accuracy of Acoustic-Based Proton Range Verification in Water

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

Jones, KC; Sehgal, CM; Avery, S

2016-06-15

Purpose: To determine the accuracy and dose required for acoustic-based proton range verification (protoacoustics) in water. Methods: Proton pulses with 17 µs FWHM and instantaneous currents of 480 nA (5.6 × 10{sup 7} protons/pulse, 8.9 cGy/pulse) were generated by a clinical, hospital-based cyclotron at the University of Pennsylvania. The protoacoustic signal generated in a water phantom by the 190 MeV proton pulses was measured with a hydrophone placed at multiple known positions surrounding the dose deposition. The background random noise was measured. The protoacoustic signal was simulated to compare to the experiments. Results: The maximum protoacoustic signal amplitude at 5more » cm distance was 5.2 mPa per 1 × 10{sup 7} protons (1.6 cGy at the Bragg peak). The background random noise of the measurement was 27 mPa. Comparison between simulation and experiment indicates that the hydrophone introduced a delay of 2.4 µs. For acoustic data collected with a signal-to-noise ratio (SNR) of 21, deconvolution of the protoacoustic signal with the proton pulse provided the most precise time-of-flight range measurement (standard deviation of 2.0 mm), but a systematic error (−4.5 mm) was observed. Conclusion: Based on water phantom measurements at a clinical hospital-based cyclotron, protoacoustics is a potential technique for measuring the proton Bragg peak range with 2.0 mm standard deviation. Simultaneous use of multiple detectors is expected to reduce the standard deviation, but calibration is required to remove systematic error. Based on the measured background noise and protoacoustic amplitude, a SNR of 5.3 is projected for a deposited dose of 2 Gy.« less

Three-particle breakup of the isobaric analog state in 17F

NASA Astrophysics Data System (ADS)

Chow, J. C.; Morton, A. C.; Azuma, R. E.; Bateman, N.; Boyd, R. N.; Buchmann, L.; D'auria, J. M.; Davinson, T.; Dombsky, M.; Galster, W.; Gete, E.; Giesen, U.; Iliadis, C.; Jackson, K. P.; King, J. D.; Roy, G.; Shoppa, T.; Shotter, A.

1998-02-01

We have studied the β-delayed particle decay of 17Ne to test the feasibility of determining both the E1 and E2 components of the 12C(α,γ)16O cross section at energies relevant to helium burning in stars. In this context we have observed the breakup of the isobaric analog state in 17F at 11.193 MeV into three particles via three channels: proton decay to the 9.59 MeV state in 16O; and α decay to the 2.365 and 3.502/3.547 MeV states in 13N. This is the first reported observation of the decay of the IAS to the 1- state in 16O at 9.59 MeV and the first reported β-delayed proton-α decay. With straightforward improvements to our detection apparatus to improve angular resolution, β suppression, and solid angle coverage, we should be able to proceed to the measurement of the effect of the tail of the subthreshold state at 7.117 MeV in 16O on the α spectrum from the breakup of the 9.59 MeV state.

Watching proton transfer in real time: Ultrafast photoionization-induced proton transfer in phenol-ammonia complex cation.

PubMed

Shen, Ching-Chi; Tsai, Tsung-Ting; Wu, Jun-Yi; Ho, Jr-Wei; Chen, Yi-Wei; Cheng, Po-Yuan

2017-10-28

In this paper, we give a full account of our previous work [C. C. Shen et al., J. Chem. Phys. 141, 171103 (2014)] on the study of an ultrafast photoionization-induced proton transfer (PT) reaction in the phenol-ammonia (PhOH-NH 3 ) complex using ultrafast time-resolved ion photofragmentation spectroscopy implemented by the photoionization-photofragmentation pump-probe detection scheme. Neutral PhOH-NH 3 complexes prepared in a free jet are photoionized by femtosecond 1 + 1 resonance-enhanced multiphoton ionization via the S 1 state. The evolving cations are then probed by delayed pulses that result in ion fragmentation, and the ionic dynamics is followed by measuring the parent-ion depletion as a function of the pump-probe delay time. By comparing with systems in which PT is not feasible and the steady-state ion photofragmentation spectra, we concluded that the observed temporal evolutions of the transient ion photofragmentation spectra are consistent with an intracomplex PT reaction after photoionization from the initial non-PT to the final PT structures. Our experiments revealed that PT in [PhOH-NH 3 ] + cation proceeds in two distinct steps: an initial impulsive wave-packet motion in ∼70 fs followed by a slower relaxation of about 1 ps that stabilizes the system into the final PT configuration. These results indicate that for a barrierless PT system, even though the initial PT motions are impulsive and ultrafast, the time scale to complete the reaction can be much slower and is determined by the rate of energy dissipation into other modes.

Watching proton transfer in real time: Ultrafast photoionization-induced proton transfer in phenol-ammonia complex cation

NASA Astrophysics Data System (ADS)

Shen, Ching-Chi; Tsai, Tsung-Ting; Wu, Jun-Yi; Ho-Wei, Jr.; Chen, Yi-Wei; Cheng, Po-Yuan

2017-10-01

In this paper, we give a full account of our previous work [C. C. Shen et al., J. Chem. Phys. 141, 171103 (2014)] on the study of an ultrafast photoionization-induced proton transfer (PT) reaction in the phenol-ammonia (PhOH-NH3) complex using ultrafast time-resolved ion photofragmentation spectroscopy implemented by the photoionization-photofragmentation pump-probe detection scheme. Neutral PhOH-NH3 complexes prepared in a free jet are photoionized by femtosecond 1 + 1 resonance-enhanced multiphoton ionization via the S1 state. The evolving cations are then probed by delayed pulses that result in ion fragmentation, and the ionic dynamics is followed by measuring the parent-ion depletion as a function of the pump-probe delay time. By comparing with systems in which PT is not feasible and the steady-state ion photofragmentation spectra, we concluded that the observed temporal evolutions of the transient ion photofragmentation spectra are consistent with an intracomplex PT reaction after photoionization from the initial non-PT to the final PT structures. Our experiments revealed that PT in [PhOH-NH3]+ cation proceeds in two distinct steps: an initial impulsive wave-packet motion in ˜70 fs followed by a slower relaxation of about 1 ps that stabilizes the system into the final PT configuration. These results indicate that for a barrierless PT system, even though the initial PT motions are impulsive and ultrafast, the time scale to complete the reaction can be much slower and is determined by the rate of energy dissipation into other modes.

[BIOLOGICAL EFFECTIVENESS OF FISSION SPECTRUM NEUTRONS AND PROTONS WITH ENERGIES OF 60-126 MEV DURING ACUTE AND PROLONGED IRRADIATION].

PubMed

Shafirkin, A V

2015-01-01

Neutrons of the fission spectrum are characterized by relatively high values of linear energy transfer (LET). Data about their effects on biological objects are used to evaluate the risk of delayed effects of accelerated ions within the same LET range that serve as an experimental model of the nuclei component of galactic cosmic rays (GCR). Additionally, risks of delayed consequences to cosmonaut's health and average lifetime from certain GCR fluxes and secondary neutrons can be also prognosticated. The article deals with comparative analysis of the literature on reduction of average lifespan (ALS) of animals exposed to neutron reactor spectrum, 60-126 MeV protons, and X- and γ-rays in a broad range of radiation intensity and duration. It was shown that a minimal lifespan reduction by 5% occurs due to a brief exposure to neutrons with the absorbed dose of 5 cGy, whereas same lifespan reduction due to hard X- and γ-radiation occurs after absorption of a minimal dose of 100 cGy. Therefore, according to the estimated minimal ALS reduction in mice, neutron effectiveness is 20-fold higher. Biological effectiveness of protons as regards ALS reduction is virtually equal to that of standard types of radiation. Exposure to X- and γ-radiation with decreasing daily doses, and increasing number of fractions and duration gives rise to an apparent trend toward a less dramatic ALS reduction in mice; on the contrary, exposure to neutrons of varying duration had no effect on threshold doses for the specified ALS reductions. Factors of relative biological effectiveness of neutrons reached 40.

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

PubMed

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

2007-02-07

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

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

PubMed Central

Vedovato, Natascia

2014-01-01

A single Na+/K+-ATPase pumps three Na+ outwards and two K+ inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na+ than K+ generates outward current across the cell membrane. Less well understood is the ability of Na+/K+ pumps to generate an inward current of protons. Originally noted in pumps deprived of external K+ and Na+ ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K+ and Na+ concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na+ release from phosphorylated Na+/K+ pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na+/K+ pumps that enables proton import is not required for completion of the 3 Na+/2 K+ transport cycle. However, the back-step occurs readily during Na+/K+ transport when external K+ ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na+-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na+ and K+ ions that passes through binding site II. The inferred occurrence of Na+/K+ exchange and H+ import during the same conformational cycle of a single molecule identifies the Na+/K+ pump as a hybrid transporter. Whether Na+/K+ pump–mediated proton inflow may have any physiological or pathophysiological significance remains to be clarified. PMID:24688018

Modelling of proton acceleration in application to a ground level enhancement

NASA Astrophysics Data System (ADS)

Afanasiev, A.; Vainio, R.; Rouillard, A. P.; Battarbee, M.; Aran, A.; Zucca, P.

2018-06-01

Context. The source of high-energy protons (above 500 MeV) responsible for ground level enhancements (GLEs) remains an open question in solar physics. One of the candidates is a shock wave driven by a coronal mass ejection, which is thought to accelerate particles via diffusive-shock acceleration. Aims: We perform physics-based simulations of proton acceleration using information on the shock and ambient plasma parameters derived from the observation of a real GLE event. We analyse the simulation results to find out which of the parameters are significant in controlling the acceleration efficiency and to get a better understanding of the conditions under which the shock can produce relativistic protons. Methods: We use the results of the recently developed technique to determine the shock and ambient plasma parameters, applied to the 17 May 2012 GLE event, and carry out proton acceleration simulations with the Coronal Shock Acceleration (CSA) model. Results: We performed proton acceleration simulations for nine individual magnetic field lines characterised by various plasma conditions. Analysis of the simulation results shows that the acceleration efficiency of the shock, i.e. its ability to accelerate particles to high energies, tends to be higher for those shock portions that are characterised by higher values of the scattering-centre compression ratio rc and/or the fast-mode Mach number MFM. At the same time, the acceleration efficiency can be strengthened by enhanced plasma density in the corresponding flux tube. The simulations show that protons can be accelerated to GLE energies in the shock portions characterised by the highest values of rc. Analysis of the delays between the flare onset and the production times of protons of 1 GV rigidity for different field lines in our simulations, and a subsequent comparison of those with the observed values indicate a possibility that quasi-perpendicular portions of the shock play the main role in producing relativistic protons.

1p3/2 proton-hole state in 132Sn and the shell structure along N = 82.

PubMed

Taprogge, J; Jungclaus, A; Grawe, H; Nishimura, S; Doornenbal, P; Lorusso, G; Simpson, G S; Söderström, P-A; Sumikama, T; Xu, Z Y; Baba, H; Browne, F; Fukuda, N; Gernhäuser, R; Gey, G; Inabe, N; Isobe, T; Jung, H S; Kameda, D; Kim, G D; Kim, Y-K; Kojouharov, I; Kubo, T; Kurz, N; Kwon, Y K; Li, Z; Sakurai, H; Schaffner, H; Steiger, K; Suzuki, H; Takeda, H; Vajta, Zs; Watanabe, H; Wu, J; Yagi, A; Yoshinaga, K; Benzoni, G; Bönig, S; Chae, K Y; Coraggio, L; Covello, A; Daugas, J-M; Drouet, F; Gadea, A; Gargano, A; Ilieva, S; Kondev, F G; Kröll, T; Lane, G J; Montaner-Pizá, A; Moschner, K; Mücher, D; Naqvi, F; Niikura, M; Nishibata, H; Odahara, A; Orlandi, R; Patel, Z; Podolyák, Zs; Wendt, A

2014-04-04

A low-lying state in 131In82, the one-proton hole nucleus with respect to double magic 132Sn, was observed by its γ decay to the Iπ=1/2- β-emitting isomer. We identify the new state at an excitation energy of Ex=1353  keV, which was populated both in the β decay of 131Cd83 and after β-delayed neutron emission from 132Cd84, as the previously unknown πp3/2 single-hole state with respect to the 132Sn core. Exploiting this crucial new experimental information, shell-model calculations were performed to study the structure of experimentally inaccessible N=82 isotones below 132Sn. The results evidence a surprising absence of proton subshell closures along the chain of N=82 isotones. The consequences of this finding for the evolution of the N=82 shell gap along the r-process path are discussed.

Time-resolved absorbance changes induced by fast acidification of bacteriorhodopsin in vesicle systems.

PubMed Central

Druckmann, S; Ottolenghi, M; Korenstein, R

1985-01-01

The direction of the accessibility to protons of the binding site in bacteriorhodopsin is of primary importance in elucidating the proton-pump mechanism. The problem is approached via the pH-dependent equilibrium bR560 in equilibrium bR605 in vesicles with preferentially oriented purple membranes. Fast acidification (stopped-flow) experiments with inside-out, monomeric, bR vesicles were carried out with and without a buffer enclosed in the vesicle interior. The results, showing a buffer-induced delay in the formation of bR605, indicate that the binding site is accessible to protons from the inside of the vesicles. We arrive at this conclusion also by working with inside-out trimeric vesicles in the presence and in the absence of H+ (and K+) ionophores. The results suggest that in Halobacterium halobium, the binding site and thus the retinal Schiff base are exposed to the outside of the cell. This conclusion is consistent with a pumping mechanism based on a light-induced pK change. PMID:3978185

Delayed effects of proton irradiation in Macaca Mulatta (22-year summary)

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

Woods, D.H.; Hardy, K.A.; Cox, A.B.

1989-05-15

Lifetime observations on a group of rhesus monkeys indicate that life expectancy loss from exposure to protons in the energy range encountered in the Van Allen belts and solar proton events can be correlated with the dose and energy of radiation. The primary cause of life shortening is nonleukemic cancers. Radiation also increased the rise of endometriosis (an abnormal proliferation of the lining of the uterus in females). Other effects associated with radiation exposures are lowered glucose tolerance and increased incidence of cataracts. Calculations of the relative risk of fatal cancers in the irradiated subjects reveal that the total bodymore » surface dose required to double the risk of death from cancer over a 20-year post exposure period varies with the linear energy transfer (LET) of the radiation. The ability to determine the integrated dose and LET spectrum in space radiation exposures of humans is, therefore, critical to the assessment of lifetime cancer risk.« less

Analysis of Giant-nucleated Cell Formation Following X-ray and Proton Irradiations

NASA Astrophysics Data System (ADS)

Almahwasi, Ashraf Abdu

Radiation-induced genetic instability has been observed in survivors of irradiated cancerous and normal cells in vitro and in vivo and has been determined in different forms, such as delayed cell death, chromosomal aberration or mutation. A well defined and characterized normal human-diploid AG1522 fibroblast cell line was used to study giant-nucleated cell (GCs) formation as the ultimate endpoint of this research. The average nuclear cross-sectional areas of the AG1522 cells were measured in mum2. The doubling time required by the AG1522 cells to divide was measured. The potential toxicity of the Hoechst dye at a working concentration on the live AG1522 cells was assessed. The yield of giant cells was determined at 7, 14 and 21 days after exposure to equivalent clinical doses of 0.2, 1 or 2 Gy of X-ray or proton irradiation. Significant differences were found to exist between X-ray or proton irradiation when compared with sham-irradiated control populations. The frequency of GCs induced by X-rays was also compared to those formed in proton irradiated cultures. The results confirm that 1 Gy X-rays are shown to induce higher rates of mitotically arrested GCs, increasing continually over time up to 21 days post-irradiation. The yield of GCs was significantly greater (10%) compared to those formed in proton populations (2%) 21 days postirradiation. The GCs can undergo a prolonged mitotic arrest that significantly increases the length of cell cycle. The arrest of GCs at the mitotic phase for longer periods of time might be indicative of a strategy for cell survival, as it increases the time available for DNA repair and enables an alternative route to division for the cells. However, the reduction in their formation 21 days after both types of radiation might favour GCs formation, ultimately contributing to carcinogenesis or cancer therapy resistance. The X-ray experiments revealed a dose-dependent increase in the GCs up to 14 days after irradiation. Although the proton irradiation was less efficient in producing GCs, their frequency was elevated in a dose-dependent manner 7 days after irradiation, with persistent expression of nuclear deformity as an indicator of genetic instability. In addition to the quantification of the GCs, the proliferation of a small fraction of giant cells formed at 14 days after 0.2 Gy of proton irradiation was observed to divide into asymmetrical, normal-sized daughter cells. These results might have important implications in evaluating risk estimates, or could act as a potential radioprotective assay for a dose-limiting parameter for delayed effects in healthy tissues during radiation therapy treatment.

Improving proton therapy accessibility through seamless electronic integration of remote treatment planning sites.

PubMed

Belard, Arnaud; Dolney, Derek; Zelig, Tochner; McDonough, James; O'Connell, John

2011-06-01

Proton radiotherapy is a relatively scarce treatment modality in radiation oncology, with only nine centers currently operating in the United States. Funded by Public Law 107-248, the University of Pennsylvania and the Walter Reed Army Medical Center have developed a remote proton radiation therapy solution with the goals of improving access to proton radiation therapy for Department of Defense (DoD) beneficiaries while minimizing treatment delays and time spent away from home/work (time savings of up to 3 weeks per patient). To meet both Health Insurance Portability and Accountability Act guidelines and the more stringent security restrictions imposed by the DoD, our program developed a hybrid remote proton radiation therapy solution merging a CITRIX server with a JITIC-certified (Joint Interoperability Test Command) desktop videoconferencing unit. This conduit, thoroughly tested over a period of 6 months, integrates both institutions' radiation oncology treatment planning infrastructures into a single entity for DoD patients' treatment planning and delivery. This telemedicine solution enables DoD radiation oncologists and medical physicists the ability to (1) remotely access a proton therapy treatment planning platform, (2) transfer patient plans securely to the University of Pennsylvania patient database, and (3) initiate ad-hoc point-to-point and multipoint videoconferences to dynamically optimize and validate treatment plans. Our robust and secure remote treatment planning solution grants DoD patients not only access to a state-of-the-art treatment modality, but also participation in the treatment planning process by Walter Reed Army Medical Center radiation oncologists and medical physicists. This telemedicine system has the potential to lead to a greater integration of military treatment facilities and/or satellite clinics into regional proton therapy centers.

Acoustic time-of-flight for proton range verification in water

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

Jones, Kevin C.; Avery, Stephen, E-mail: Stephen.A

2016-09-15

Purpose: Measurement of the arrival times of thermoacoustic waves induced by pulsed proton dose depositions (protoacoustics) may provide a proton range verification method. The goal of this study is to characterize the required dose and protoacoustic proton range (distance) verification accuracy in a homogeneous water medium at a hospital-based clinical cyclotron. Methods: Gaussian-like proton pulses with 17 μs widths and instantaneous currents of 480 nA (5.6 × 10{sup 7} protons/pulse, 3.4 cGy/pulse at the Bragg peak) were generated by modulating the cyclotron proton source with a function generator. After energy degradation, the 190 MeV proton pulses irradiated a water phantom,more » and the generated protoacoustic emissions were measured by a hydrophone. The detector position and proton pulse characteristics were varied. The experimental results were compared to simulations. Different arrival time metrics derived from acoustic waveforms were compared, and the accuracy of protoacoustic time-of-flight distance calculations was assessed. Results: A 27 mPa noise level was observed in the treatment room during irradiation. At 5 cm from the proton beam, an average maximum pressure of 5.2 mPa/1 × 10{sup 7} protons (6.1 mGy at the Bragg peak) was measured after irradiation with a proton pulse with 10%–90% rise time of 11 μs. Simulation and experiment arrival times agreed well, and the observed 2.4 μs delay between simulation and experiment is attributed to the difference between the hydrophone’s acoustic and geometric centers. Based on protoacoustic arrival times, the beam axis position was measured to within (x, y) = (−2.0,  0.5) ± 1 mm. After deconvolution of the exciting proton pulse, the protoacoustic compression peak provided the most consistent measure of the distance to the Bragg peak, with an error distribution with mean = − 4.5 mm and standard deviation = 2.0 mm. Conclusions: Based on water tank measurements at a clinical hospital-based cyclotron, protoacoustics is a potential method for measuring the beam’s position (x and y within 2.0 mm) and Bragg peak range (2.0 mm standard deviation), although range verification will require simulation or experimental calibration to remove systematic error. Based on extrapolation, a protoacoustic arrival time reproducibility of 1.5 μs (2.2 mm) is achievable with 2 Gy of total deposited dose. Of the compared methods, deconvolution of the excitation proton pulse is the best technique for extracting protoacoustic arrival times, particularly if there is variation in the proton pulse shape.« less

Acoustic time-of-flight for proton range verification in water.

PubMed

Jones, Kevin C; Vander Stappen, François; Sehgal, Chandra M; Avery, Stephen

2016-09-01

Measurement of the arrival times of thermoacoustic waves induced by pulsed proton dose depositions (protoacoustics) may provide a proton range verification method. The goal of this study is to characterize the required dose and protoacoustic proton range (distance) verification accuracy in a homogeneous water medium at a hospital-based clinical cyclotron. Gaussian-like proton pulses with 17 μs widths and instantaneous currents of 480 nA (5.6 × 10(7) protons/pulse, 3.4 cGy/pulse at the Bragg peak) were generated by modulating the cyclotron proton source with a function generator. After energy degradation, the 190 MeV proton pulses irradiated a water phantom, and the generated protoacoustic emissions were measured by a hydrophone. The detector position and proton pulse characteristics were varied. The experimental results were compared to simulations. Different arrival time metrics derived from acoustic waveforms were compared, and the accuracy of protoacoustic time-of-flight distance calculations was assessed. A 27 mPa noise level was observed in the treatment room during irradiation. At 5 cm from the proton beam, an average maximum pressure of 5.2 mPa/1 × 10(7) protons (6.1 mGy at the Bragg peak) was measured after irradiation with a proton pulse with 10%-90% rise time of 11 μs. Simulation and experiment arrival times agreed well, and the observed 2.4 μs delay between simulation and experiment is attributed to the difference between the hydrophone's acoustic and geometric centers. Based on protoacoustic arrival times, the beam axis position was measured to within (x, y) = (-2.0,  0.5) ± 1 mm. After deconvolution of the exciting proton pulse, the protoacoustic compression peak provided the most consistent measure of the distance to the Bragg peak, with an error distribution with mean = - 4.5 mm and standard deviation = 2.0 mm. Based on water tank measurements at a clinical hospital-based cyclotron, protoacoustics is a potential method for measuring the beam's position (x and y within 2.0 mm) and Bragg peak range (2.0 mm standard deviation), although range verification will require simulation or experimental calibration to remove systematic error. Based on extrapolation, a protoacoustic arrival time reproducibility of 1.5 μs (2.2 mm) is achievable with 2 Gy of total deposited dose. Of the compared methods, deconvolution of the excitation proton pulse is the best technique for extracting protoacoustic arrival times, particularly if there is variation in the proton pulse shape.

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.

Energetic Particle Propagation in the Inner Heliosphere as Deduced from Low Frequency (less than 100 kHz) Observations of Type III Radio Bursts

NASA Technical Reports Server (NTRS)

Cane, H. V.; Erickson, W. C.

2003-01-01

Solar energetic particle (SEP) events are well-associated with solar flares. It is observed that the delay between the time of the flare and the first-arriving particles at a spacecraft increases with increasing difference between the flare longitude and the footpoint of the field line on which the spacecraft is located. This difference we call the "connection angle" and can be as large as approximately 120 deg. Recently it has been found that all SEP events are preceded by type III radio bursts. These bursts are plasma emission caused by the propagation of 2-50 keV flare electrons through the solar corona and into the solar wind. The drift of these type III radio bursts to lower and lower frequencies enables the propagation of the flare electrons to be traced from the Sun to about 1 AU. We have made an extensive analysis of the type III bursts associated with greater than 20 MeV proton events and find that, in most cases, the radio emission extends to the local plasma frequency when the energetic particles arrive within a few hours of the flare. We conclude that this emission at the lowest possible frequency is generated close to the spacecraft. We then use the time from when the burst started at the Sun to when it reached the local plasma frequency to infer the time it took the radio producing electrons to travel to the spacecraft. We find that these delay times are organized by the connection angle and correlate with the proton delay times. We also find that the differences between the radio delays at Wind and Ulysses are matched by differences in the relative arrival times of the energetic particles at the two spacecraft. The consistent timing between the relative arrival times of energetic electrons and protons and the start of the lowest frequency radio emissions suggests that the first arriving particles of both species are accelerated as part of the flare process and that they propagate to the spacecraft along trajectories similar to those of the lower energy flare electrons. To be detected by observers at locations distant from the nominal field lines originating in the flaring regions the particles must undergo lateral transport. The continuity of the radio bursts suggests that the cross-field transport may occur in the interplanetary medium.

Dynamics-based selective 2D 1H/1H chemical shift correlation spectroscopy under ultrafast MAS conditions

NASA Astrophysics Data System (ADS)

Zhang, Rongchun; Ramamoorthy, Ayyalusamy

2015-05-01

Dynamics plays important roles in determining the physical, chemical, and functional properties of a variety of chemical and biological materials. However, a material (such as a polymer) generally has mobile and rigid regions in order to have high strength and toughness at the same time. Therefore, it is difficult to measure the role of mobile phase without being affected by the rigid components. Herein, we propose a highly sensitive solid-state NMR approach that utilizes a dipolar-coupling based filter (composed of 12 equally spaced 90° RF pulses) to selectively measure the correlation of 1H chemical shifts from the mobile regions of a material. It is interesting to find that the rotor-synchronized dipolar filter strength decreases with increasing inter-pulse delay between the 90° pulses, whereas the dipolar filter strength increases with increasing inter-pulse delay under static conditions. In this study, we also demonstrate the unique advantages of proton-detection under ultrafast magic-angle-spinning conditions to enhance the spectral resolution and sensitivity for studies on small molecules as well as multi-phase polymers. Our results further demonstrate the use of finite-pulse radio-frequency driven recoupling pulse sequence to efficiently recouple weak proton-proton dipolar couplings in the dynamic regions of a molecule and to facilitate the fast acquisition of 1H/1H correlation spectrum compared to the traditional 2D NOESY (Nuclear Overhauser effect spectroscopy) experiment. We believe that the proposed approach is beneficial to study mobile components in multi-phase systems, such as block copolymers, polymer blends, nanocomposites, heterogeneous amyloid mixture of oligomers and fibers, and other materials.

Delayed effects of proton irradiation in Macaca mulatta. II. Mortality (15-year report). Interim report 1964-1982

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

Yochmowitz, M.G.; Wood, D.H.; Salmon, Y.L.

1983-01-01

A radiation primate colony of 57 controls and 301 (217 proton) exposed subjects has been followed since 1964. Lifespan of both the exposed and, more specifically, the proton-exposed subjects in the chronic colony was shortened. Energies of 55 MeV and greater decreased life span as did doses in excess of 360 rads. Females were more sensitive to lower doses than males. They died earlier in doses as low as 25-113 rads and in all energies tested except 55 MeV. Survival curve analysis found no difference among the onset of death in the 3 highest energies (138, 400, and 2300 Mev);more » however, its onset was earlier in the 32-MeV exposure and later in the 55-MeV exposure and later in the 55-MeV exposure than the total penetrating energies (greater than or equal to 138 MeV). Dose ordering effects were evident. In contrast to the controls, mortality rates began to accelerate at approx. 8 years in the 360-400-rad group; at approx. 2 years in the 500-650-rad group and approx. 1 year in the 800-rad group. The leading causes of death among the proton-exposed animals were primary infections (approx. 30%), endometriosis (25%), and organ degeneration (approx. 17%). Malignant tumors accounted for 18% of the deaths. If endometriosis is included in this group, the mortality from all forms of neoplastic conditions is 43% in the proton-exposed animals.« less

Delayed effects of proton irradiation in Macaca mulatta. II. mortality (15-year report). Interim report 1964-1982

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

Yochmowitz, M.G.; Wood, D.H.; Salmon, Y.L.

1983-01-01

A radiation primate colony of 57 controls and 301 (217 proton) exposed subjects has been followed since 1964. Lifespan of both the exposed and, more specifically, the proton-exposed subjects in the chronic colony was shortened. Energies of 55 MeV and greater decreased life span as did doses in excess of 360 rads. Females were more sensitive to lower doses than males. They died earlier in doses as low as 25-113 rads and in all energies tested except 55 MeV. Survival curve analysis found no difference among the onset of death in the 3 highest energies (138, 400, and 2300 Mev);more » however, its onset was earlier in the 32-MeV exposure and later in the 55-MeV exposure and later in the 55-MeV exposure than the total penetrating energies (greater than or equal to 138 MeV). Dose ordering effects were evident. In contrast to the controls, mortality rates began to accelerate at approx. 8 years in the 360-400-rad group; at approx. 2 years in the 500-650-rad group and approx. 1 year in the 800-rad group. The leading causes of death among the proton-exposed animals were primary infections (approx. 30%), endometriosis (25%), and organ degeneration (approx. 17%). Malignant tumors accounted for 18% of the deaths. If endometriosis is included in this group, the mortality from all forms of neoplastic conditions is 43% in the proton-exposed animals.« less

Influence of gastric emptying on gastro-esophageal reflux: a combined pH-impedance study.

PubMed

Gourcerol, G; Benanni, Y; Boueyre, E; Leroi, A M; Ducrotte, P

2013-10-01

The involvement of delayed gastric emptying (GE) in the pathophysiology of gastro-esophageal reflux disease (GERD) remains debated and has been to date only assessed using esophageal pH-metry that only detects acidic reflux. We therefore investigated whether delay in GE could impact on liquid, mixed, and gas reflux detected using combined esophageal pH-impedance recording. Thirty consecutive patients were explored with GE and esophageal pH-impedance measurement in the workup of typical symptoms of GERD. Gastric emptying was assessed using the (13) C-octanoic acid breath test and an ambulatory esophageal pH-impedance recording was performed off proton pump inhibitors (PPIs) for 24 h. Gastric emptying was normal in 17 patients and delayed in 13 patients. Delay in GE increased the daily number of liquid/mixed reflux events detected by combined esophageal pH-impedance monitoring, but had no effect of esophageal acid exposure or gas reflux. This translated in increased number of postprandial reflux events, with a longer bolus clearance time and increased esophageal proximal extension. In patient with delayed GE, symptomatic reflux had a higher proximal extension and a longer bolus clearance time compared to symptomatic reflux events from patients with normal GE. Delay in GE increases daily and postprandial liquid/mixed reflux events. Reflux characteristics differently trigger symptoms in patients with normal and delayed GE, and may impact on the therapeutic strategy. © 2013 John Wiley & Sons Ltd.

The mutable nature of particle-core excitations with spin in the one-valence-proton nucleus 133Sb

NASA Astrophysics Data System (ADS)

Bocchi, G.; Leoni, S.; Fornal, B.; Colò, G.; Bortignon, P. F.; Bottoni, S.; Bracco, A.; Michelagnoli, C.; Bazzacco, D.; Blanc, A.; de France, G.; Jentschel, M.; Köster, U.; Mutti, P.; Régis, J.-M.; Simpson, G.; Soldner, T.; Ur, C. A.; Urban, W.; Fraile, L. M.; Lozeva, R.; Belvito, B.; Benzoni, G.; Bruce, A.; Carroll, R.; Cieplicka-Oryǹczak, N.; Crespi, F. C. L.; Didierjean, F.; Jolie, J.; Korten, W.; Kröll, T.; Lalkovski, S.; Mach, H.; Mărginean, N.; Melon, B.; Mengoni, D.; Million, B.; Nannini, A.; Napoli, D.; Olaizola, B.; Paziy, V.; Podolyák, Zs.; Regan, P. H.; Saed-Samii, N.; Szpak, B.; Vedia, V.

2016-09-01

The γ-ray decay of excited states of the one-valence-proton nucleus 133Sb has been studied using cold-neutron induced fission of 235U and 241Pu targets, during the EXILL campaign at the ILL reactor in Grenoble. By using a highly efficient HPGe array, coincidences between γ-rays prompt with the fission event and those delayed up to several tens of microseconds were investigated, allowing to observe, for the first time, high-spin excited states above the 16.6 μs isomer. Lifetimes analysis, performed by fast-timing techniques with LaBr3(Ce) scintillators, revealed a difference of almost two orders of magnitude in B(M1) strength for transitions between positive-parity medium-spin yrast states. The data are interpreted by a newly developed microscopic model which takes into account couplings between core excitations (both collective and non-collective) of the doubly magic nucleus 132Sn and the valence proton, using the Skyrme effective interaction in a consistent way. The results point to a fast change in the nature of particle-core excitations with increasing spin.

Structural defect accumulation in tungsten and tungsten-5wt.% tantalum under incremental proton damage

NASA Astrophysics Data System (ADS)

Ipatova, I.; Harrison, R. W.; Wady, P. T.; Shubeita, S. M.; Terentyev, D.; Donnelly, S. E.; Jimenez-Melero, E.

2018-04-01

We have performed proton irradiation of W and W-5wt.%Ta materials at 350 °C with a step-wise damage level increase up to 0.7 dpa and using two beam energies, namely 40 keV and 3 MeV, in order to probe the accumulation of radiation-induced lattice damage in these materials. Interstitial-type a/2 <111> dislocation loops are formed under irradiation, and their size increases in W-5Ta up to a loop width of 21 ± 4 nm at 0.3 dpa, where loop saturation takes place. In contrast, the loop length in W increases progressively up to 183 ± 50 nm at 0.7 dpa, whereas the loop width remains relatively constant at 29 ± 7 nm at >0.3 dpa, giving rise to dislocation strings. The dislocation loops and tangles are observed in both materials examined after a 3 MeV proton irradiation at 350 °C. Ta doping delays the evolution of radiation-induced dislocation structures in W, and can consequently impact the hydrogen isotope retention under plasma exposure.

In vitro dissolution of proton-pump inhibitor products intended for paediatric and geriatric use in physiological bicarbonate buffer.

PubMed

Liu, Fang; Shokrollahi, Honaz

2015-05-15

Proton-pump inhibitor (PPI) products based on enteric coated multiparticulates are design to meet the needs of patients who cannot swallow tablets such as children and older adults. Enteric coated PPI preparations exhibit delays in in vivo absorption and onset of antisecretory effects, which is not reflected by the rapid in vitro dissolution in compendial pH 6.8 phosphate buffer commonly used for assessment of these products. A more representative and physiological medium, pH 6.8 mHanks bicarbonate buffer, was used in this study to evaluate the in vitro dissolution of enteric coated multiparticulate-based PPI products. Commercially available omeprazole, lansoprazole and esomeprazole products were subject to dissolution tests using USP-II apparatus in pH 4.5 phosphate buffer saline for 45 min (acid stage) followed by pH 6.8 phosphate buffer or pH 6.8 mHanks bicarbonate buffer. In pH 6.8 phosphate buffer, all nine tested products displayed rapid and comparable dissolution profiles meeting the pharmacopeia requirements for delayed release preparations. In pH 6.8 mHanks buffer, drug release was delayed and failed the pharmacopeia requirements from most enteric coated preparations. Despite that the same enteric polymer, methacrylic acid-ethyl acrylate copolymer (1:1), was applied to all commercial multiparticulate-based products, marked differences were observed between dissolution profiles of these preparations. The use of pH 6.8 physiological bicarbonate (mHanks) buffer can serve as a useful tool to provide realistic and discriminative in vitro release assessment of enteric coated PPI preparations and to assist rational formulation development of these products. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Madrak, R.; Wildman, D.

The key elements have been constructed for a fast chopper system capable of removing single 2.5 MeV proton bunches spaced at 325 MHz. The average chopping rate is ~ 1 MHz. The components include a pulse delaying microstrip structure for deflecting the beam, high voltage (1.2 kV) fast (ns rise time) pulsers, and an associated wideband combiner. Various designs for the deflecting structures have been studied. Measurements of the microstrip structures' coverage factors and pulse shapes are presented.

Modeling of proton-induced radioactivation background in hard X-ray telescopes: Geant4-based simulation and its demonstration by Hitomi's measurement in a low Earth orbit

NASA Astrophysics Data System (ADS)

Odaka, Hirokazu; Asai, Makoto; Hagino, Kouichi; Koi, Tatsumi; Madejski, Greg; Mizuno, Tsunefumi; Ohno, Masanori; Saito, Shinya; Sato, Tamotsu; Wright, Dennis H.; Enoto, Teruaki; Fukazawa, Yasushi; Hayashi, Katsuhiro; Kataoka, Jun; Katsuta, Junichiro; Kawaharada, Madoka; Kobayashi, Shogo B.; Kokubun, Motohide; Laurent, Philippe; Lebrun, Francois; Limousin, Olivier; Maier, Daniel; Makishima, Kazuo; Mimura, Taketo; Miyake, Katsuma; Mori, Kunishiro; Murakami, Hiroaki; Nakamori, Takeshi; Nakano, Toshio; Nakazawa, Kazuhiro; Noda, Hirofumi; Ohta, Masayuki; Ozaki, Masanobu; Sato, Goro; Sato, Rie; Tajima, Hiroyasu; Takahashi, Hiromitsu; Takahashi, Tadayuki; Takeda, Shin'ichiro; Tanaka, Takaaki; Tanaka, Yasuyuki; Terada, Yukikatsu; Uchiyama, Hideki; Uchiyama, Yasunobu; Watanabe, Shin; Yamaoka, Kazutaka; Yasuda, Tetsuya; Yatsu, Yoichi; Yuasa, Takayuki; Zoglauer, Andreas

2018-05-01

Hard X-ray astronomical observatories in orbit suffer from a significant amount of background due to radioactivation induced by cosmic-ray protons and/or geomagnetically trapped protons. Within the framework of a full Monte Carlo simulation, we present modeling of in-orbit instrumental background which is dominated by radioactivation. To reduce the computation time required by straightforward simulations of delayed emissions from activated isotopes, we insert a semi-analytical calculation that converts production probabilities of radioactive isotopes by interaction of the primary protons into decay rates at measurement time of all secondary isotopes. Therefore, our simulation method is separated into three steps: (1) simulation of isotope production, (2) semi-analytical conversion to decay rates, and (3) simulation of decays of the isotopes at measurement time. This method is verified by a simple setup that has a CdTe semiconductor detector, and shows a 100-fold improvement in efficiency over the straightforward simulation. To demonstrate its experimental performance, the simulation framework was tested against data measured with a CdTe sensor in the Hard X-ray Imager onboard the Hitomi X-ray Astronomy Satellite, which was put into a low Earth orbit with an altitude of 570 km and an inclination of 31°, and thus experienced a large amount of irradiation from geomagnetically trapped protons during its passages through the South Atlantic Anomaly. The simulation is able to treat full histories of the proton irradiation and multiple measurement windows. The simulation results agree very well with the measured data, showing that the measured background is well described by the combination of proton-induced radioactivation of the CdTe detector itself and thick Bi4Ge3O12 scintillator shields, leakage of cosmic X-ray background and albedo gamma-ray radiation, and emissions from naturally contaminated isotopes in the detector system.

Modeling of proton-induced radioactivation background in hard X-ray telescopes: Geant4-based simulation and its demonstration by Hitomi ’s measurement in a low Earth orbit

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

Odaka, Hirokazu; Asai, Makoto; Hagino, Kouichi

Hard X-ray astronomical observatories in orbit suffer from a significant amount of background due to radioactivation induced by cosmic-ray protons and/or geomagnetically trapped protons. Within the framework of a full Monte Carlo simulation, we present modeling of in-orbit instrumental background which is dominated by radioactivation. To reduce the computation time required by straightforward simulations of delayed emissions from activated isotopes, we insert a semi-analytical calculation that converts production probabilities of radioactive isotopes by interaction of the primary protons into decay rates at measurement time of all secondary isotopes. Therefore, our simulation method is separated into three steps: (1) simulation ofmore » isotope production, (2) semi-analytical conversion to decay rates, and (3) simulation of decays of the isotopes at measurement time. This method is verified by a simple setup that has a CdTe semiconductor detector, and shows a 100-fold improvement in efficiency over the straightforward simulation. To demonstrate its experimental performance, the simulation framework was tested against data measured with a CdTe sensor in the Hard X-ray Imager onboard the Hitomi X-ray Astronomy Satellite, which was put into a low Earth orbit with an altitude of 570 km and an inclination of 31°, and thus experienced a large amount of irradiation from geomagnetically trapped protons during its passages through the South Atlantic Anomaly. The simulation is able to treat full histories of the proton irradiation and multiple measurement windows. As a result, the simulation results agree very well with the measured data, showing that the measured background is well described by the combination of proton-induced radioactivation of the CdTe detector itself and thick Bi 4Ge 3O 12 scintillator shields, leakage of cosmic X-ray background and albedo gamma-ray radiation, and emissions from naturally contaminated isotopes in the detector system.« less

Modeling of proton-induced radioactivation background in hard X-ray telescopes: Geant4-based simulation and its demonstration by Hitomi ’s measurement in a low Earth orbit

DOE PAGES

Odaka, Hirokazu; Asai, Makoto; Hagino, Kouichi; ...

2018-02-19

Hard X-ray astronomical observatories in orbit suffer from a significant amount of background due to radioactivation induced by cosmic-ray protons and/or geomagnetically trapped protons. Within the framework of a full Monte Carlo simulation, we present modeling of in-orbit instrumental background which is dominated by radioactivation. To reduce the computation time required by straightforward simulations of delayed emissions from activated isotopes, we insert a semi-analytical calculation that converts production probabilities of radioactive isotopes by interaction of the primary protons into decay rates at measurement time of all secondary isotopes. Therefore, our simulation method is separated into three steps: (1) simulation ofmore » isotope production, (2) semi-analytical conversion to decay rates, and (3) simulation of decays of the isotopes at measurement time. This method is verified by a simple setup that has a CdTe semiconductor detector, and shows a 100-fold improvement in efficiency over the straightforward simulation. To demonstrate its experimental performance, the simulation framework was tested against data measured with a CdTe sensor in the Hard X-ray Imager onboard the Hitomi X-ray Astronomy Satellite, which was put into a low Earth orbit with an altitude of 570 km and an inclination of 31°, and thus experienced a large amount of irradiation from geomagnetically trapped protons during its passages through the South Atlantic Anomaly. The simulation is able to treat full histories of the proton irradiation and multiple measurement windows. As a result, the simulation results agree very well with the measured data, showing that the measured background is well described by the combination of proton-induced radioactivation of the CdTe detector itself and thick Bi 4Ge 3O 12 scintillator shields, leakage of cosmic X-ray background and albedo gamma-ray radiation, and emissions from naturally contaminated isotopes in the detector system.« less

Acute Biological Effects of Simulating the Whole-Body Radiation Dose Distribution from a Solar Particle Event Using a Porcine Model

PubMed Central

Wilson, Jolaine M.; Sanzari, Jenine K.; Diffenderfer, Eric S.; Yee, Stephanie S.; Seykora, John T.; Maks, Casey; Ware, Jeffrey H.; Litt, Harold I.; Reetz, Jennifer A.; McDonough, James; Weissman, Drew; Kennedy, Ann R.; Cengel, Keith A.

2011-01-01

In a solar particle event (SPE), an unshielded astronaut would receive proton radiation with an energy profile that produces a highly inhomogeneous dose distribution (skin receiving a greater dose than internal organs). The novel concept of using megavoltage electron-beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation has been described previously. Here, Yucatan minipigs were used to determine the effects of a superficial, SPE-like proton dose distribution using megavoltage electrons. In these experiments, dose-dependent increases in skin pigmentation, ulceration, keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy radiation) developed symptomatic, radiation-associated pneumonopathy approximately 90 days postirradiation. The three animals from the highest dose group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis. Moreover, delayed-type hypersensitivity was found to be altered, suggesting that superficial irradiation of the skin with ionizing radiation might cause immune dysfunction or dysregulation. In conclusion, using total doses, patterns of dose distribution, and dose rates that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities that were qualitatively different from toxicities previously reported in pigs for homogeneously delivered radiation at similar doses. PMID:21859326

Development of a β-delayed charged particle detector for studying novae and x-ray bursts

NASA Astrophysics Data System (ADS)

Friedman, Moshe; Budner, Tamas; Cortesi, Marco; Harris, Madison; Janasik, Molly; Perez-Loureiro, David; Pollaco, Emmanuel; Roosa, Michael; Tiwari, Pranjal; Wrede, Chris; Yurkon, John

2017-09-01

Classical novae and type I x-ray bursts are energetic and common thermonuclear astrophysical explosions. However, our ability to understand these events is limited by the lack of comprehensive nuclear data on proton-rich nuclei. Specifically, constraining the 30P(p , γ) 31S and 15O(α , γ) 19N e reaction rates has been found to be crucial to the understanding of nucleosynthesis and energy generation in these events. As direct measurements of these reactions are not technically feasible at the present time, a gas-filled detector of β-delayed charged particles has been designed and built to measure the 31Cl(βp) 30P and 20Mg(βpα) 15O decay sequences at NSCL, providing an indirect probe of resonances in the radiative capture reactions above. The detector is coupled with the Segmented Germanium Array (SeGA) to enable coincidence γ detection, as an additional probe of interaction details and for normalization purposes. The first phase of the detector functions as a proton calorimeter and it is currently being tested and optimized. We will describe the technical status of Phase I, including the concept, simulations, design, assembly, and first offline measurements using radioactive sources. This work is supported by NSF Grant No. PHY-1102511 and DOE Award No. DE-SC0016052.

SU-E-T-264: Preliminary Results On New Optically Stimulated Luminescent Materials for Proton Therapy Dosimetry

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

Doull, B; Zheng, Y; Procure Proton Therapy Center, Oklahoma City, OK

2014-06-01

Purpose: The objective of this work is to test the premise that luminescence materials with less under-response to proton beams can be identified by testing their dose response to low-LET radiation. The goal is to develop new Optically Stimulated Luminescence (OSL) materials with improved response for proton therapy dosimetry. Methods: We first measured the dose response of new OSL materials, synthesized in our laboratory, to low-LET radiation (beta rays from a {sup 90}Sr/{sup 90}Y source) and selected two materials having different OSL saturation characteristics and good dosimetric properties, namely MgB4O7:Ce,Li and MgO:Li. Commercial Al2O3:C was also used for comparison. Thesemore » materials were then irradiated at several depths along a pristine proton beam. The luminescence responses of the materials, relative to the entrance response, were compared with the depth dose profile measured by a multiple-layer ion chamber. Results: The OSL signals of MgB4O7:Ce,Li and MgO:Li were characterized for signal stability, dose response, and response to a clinical proton beam. The materials were also compared with the commercial Al2O3:C. The signals from both MgB4O7:Ce,Li and MgO:Li were relatively stable after a one day delay following irradiation. The low-LET dose response of the materials showed that, over the dose range investigated (up to ∼800 Gy), MgB4O7:Ce,Li did not saturate, whereas MgO:Li and Al2O3:C saturated at doses of ∼100 Gy. MgB4O7:Ce,Li showed less underresponse to proton beams than MgO:Li and Al2O3:C. Conclusion: In general the material with the highest saturation doses for low-LET radiation (MgB4O7:Ce,Li) showed the least under-response to proton beams, which suggests that it may be possible to develop better OSL materials for proton dosimetry if the dose response can be controlled during synthesis. Nevertheless, the degree in which the response to proton beams can be controlled remains to be determined. The research is funded by the Oklahoma Center for the Advancement of Science and Technology (OCAST), project number HR12-055.« less

Signature-based search for delayed photons in exclusive photon plus missing transverse energy events from pp¯ collisions with s=1.96TeV

NASA Astrophysics Data System (ADS)

Aaltonen, T.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Appel, J. A.; Arisawa, T.; Artikov, A.; Asaadi, J.; Ashmanskas, W.; Auerbach, B.; Aurisano, A.; Azfar, F.; Badgett, W.; Bae, T.; Barbaro-Galtieri, A.; Barnes, V. E.; Barnett, B. A.; Barria, P.; Bartos, P.; Bauce, M.; Bedeschi, F.; Behari, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Beretvas, A.; Bhatti, A.; Bland, K. R.; Blumenfeld, B.; Bocci, A.; Bodek, A.; Bortoletto, D.; Boudreau, J.; Boveia, A.; Brigliadori, L.; Bromberg, C.; Brucken, E.; Budagov, J.; Budd, H. S.; Burkett, K.; Busetto, G.; Bussey, P.; Butti, P.; Buzatu, A.; Calamba, A.; Camarda, S.; Campanelli, M.; Canelli, F.; Carls, B.; Carlsmith, D.; Carosi, R.; Carrillo, S.; Casal, B.; Casarsa, M.; Castro, A.; Catastini, P.; Cauz, D.; Cavaliere, V.; Cavalli-Sforza, M.; Cerri, A.; Cerrito, L.; Chen, Y. C.; Chertok, M.; Chiarelli, G.; Chlachidze, G.; Cho, K.; Chokheli, D.; Ciocci, M. A.; Clark, A.; Clarke, C.; Convery, M. E.; Conway, J.; Corbo, M.; Cordelli, M.; Cox, C. A.; Cox, D. J.; Cremonesi, M.; Cruz, D.; Cuevas, J.; Culbertson, R.; d'Ascenzo, N.; Datta, M.; De Barbaro, P.; Demortier, L.; Deninno, M.; d'Errico, M.; Devoto, F.; Di Canto, A.; Di Ruzza, B.; Dittmann, J. R.; D'Onofrio, M.; Donati, S.; Dorigo, M.; Driutti, A.; Ebina, K.; Edgar, R.; Elagin, A.; Erbacher, R.; Errede, S.; Esham, B.; Eusebi, R.; Farrington, S.; Fernández Ramos, J. P.; Field, R.; Flanagan, G.; Forrest, R.; Franklin, M.; Freeman, J. C.; Frisch, H.; Funakoshi, Y.; Garfinkel, A. F.; Garosi, P.; Gerberich, H.; Gerchtein, E.; Giagu, S.; Giakoumopoulou, V.; Gibson, K.; Ginsburg, C. M.; Giokaris, N.; Giromini, P.; Giurgiu, G.; Glagolev, V.; Glenzinski, D.; Gold, M.; Goldin, D.; Golossanov, A.; Gomez, G.; Gomez-Ceballos, G.; Goncharov, M.; González López, O.; Gorelov, I.; Goshaw, A. T.; Goulianos, K.; Gramellini, E.; Grinstein, S.; Grosso-Pilcher, C.; Group, R. C.; Guimaraes da Costa, J.; Hahn, S. R.; Han, J. Y.; Happacher, F.; Hara, K.; Hare, M.; Harr, R. F.; Harrington-Taber, T.; Hatakeyama, K.; Hays, C.; Heinrich, J.; Herndon, M.; Hocker, A.; Hong, Z.; Hopkins, W.; Hou, S.; Hughes, R. E.; Husemann, U.; Hussein, M.; Huston, J.; Introzzi, G.; Iori, M.; Ivanov, A.; James, E.; Jang, D.; Jayatilaka, B.; Jeon, E. J.; Jindariani, S.; Jones, M.; Joo, K. K.; Jun, S. Y.; Junk, T. R.; Kambeitz, M.; Kamon, T.; Karchin, P. E.; Kasmi, A.; Kato, Y.; Ketchum, W.; Keung, J.; Kilminster, B.; Kim, D. H.; Kim, H. S.; Kim, J. E.; Kim, M. J.; Kim, S. B.; Kim, S. H.; Kim, Y. J.; Kim, Y. K.; Kimura, N.; Kirby, M.; Knoepfel, K.; Kondo, K.; Kong, D. J.; Konigsberg, J.; Kotwal, A. V.; Kreps, M.; Kroll, J.; Kruse, M.; Kuhr, T.; Kurata, M.; Laasanen, A. T.; Lammel, S.; Lancaster, M.; Lannon, K.; Latino, G.; Lee, H. S.; Lee, J. S.; Leo, S.; Leone, S.; Lewis, J. D.; Limosani, A.; Lipeles, E.; Lister, A.; Liu, H.; Liu, Q.; Liu, T.; Lockwitz, S.; Loginov, A.; Lucà, A.; Lucchesi, D.; Lueck, J.; Lujan, P.; Lukens, P.; Lungu, G.; Lys, J.; Lysak, R.; Madrak, R.; Maestro, P.; Malik, S.; Manca, G.; Manousakis-Katsikakis, A.; Margaroli, F.; Marino, P.; Martínez, M.; Matera, K.; Mattson, M. E.; Mazzacane, A.; Mazzanti, P.; McNulty, R.; Mehta, A.; Mehtala, P.; Mesropian, C.; Miao, T.; Mietlicki, D.; Mitra, A.; Miyake, H.; Moed, S.; Moggi, N.; Moon, C. S.; Moore, R.; Morello, M. J.; Mukherjee, A.; Muller, Th.; Murat, P.; Mussini, M.; Nachtman, J.; Nagai, Y.; Naganoma, J.; Nakano, I.; Napier, A.; Nett, J.; Neu, C.; Nigmanov, T.; Nodulman, L.; Noh, S. Y.; Norniella, O.; Oakes, L.; Oh, S. H.; Oh, Y. D.; Oksuzian, I.; Okusawa, T.; Orava, R.; Ortolan, L.; Pagliarone, C.; Palencia, E.; Palni, P.; Papadimitriou, V.; Parker, W.; Pauletta, G.; Paulini, M.; Paus, C.; Phillips, T. J.; Piacentino, G.; Pianori, E.; Pilot, J.; Pitts, K.; Plager, C.; Pondrom, L.; Poprocki, S.; Potamianos, K.; Pranko, A.; Prokoshin, F.; Ptohos, F.; Punzi, G.; Ranjan, N.; Redondo Fernández, I.; Renton, P.; Rescigno, M.; Rimondi, F.; Ristori, L.; Robson, A.; Rodriguez, T.; Rolli, S.; Ronzani, M.; Roser, R.; Rosner, J. L.; Ruffini, F.; Ruiz, A.; Russ, J.; Rusu, V.; Sakumoto, W. K.; Sakurai, Y.; Santi, L.; Sato, K.; Saveliev, V.; Savoy-Navarro, A.; Schlabach, P.; Schmidt, E. E.; Schwarz, T.; Scodellaro, L.; Scuri, F.; Seidel, S.; Seiya, Y.; Semenov, A.; Sforza, F.; Shalhout, S. Z.; Shears, T.; Shepard, P. F.; Shimojima, M.; Shochet, M.; Shreyber-Tecker, I.; Simonenko, A.; Sinervo, P.; Sliwa, K.; Smith, J. R.; Snider, F. D.; Song, H.; Sorin, V.; Stancari, M.; Denis, R. St.; Stelzer, B.; Stelzer-Chilton, O.; Stentz, D.; Strologas, J.; Sudo, Y.; Sukhanov, A.; Suslov, I.; Takemasa, K.; Takeuchi, Y.; Tang, J.; Tecchio, M.; Teng, P. K.; Thom, J.; Thomson, E.; Thukral, V.; Toback, D.; Tokar, S.; Tollefson, K.; Tomura, T.; Tonelli, D.; Torre, S.; Torretta, D.; Totaro, P.; Trovato, M.; Ukegawa, F.; Uozumi, S.; Vázquez, F.; Velev, G.; Vellidis, C.; Vernieri, C.; Vidal, M.; Vilar, R.; Vizán, J.; Vogel, M.; Volpi, G.; Wagner, P.; Wallny, R.; Wang, S. M.; Warburton, A.; Waters, D.; Wester, W. C., III; Whiteson, D.; Wicklund, A. B.; Wilbur, S.; Williams, H. H.; Wilson, J. S.; Wilson, P.; Winer, B. L.; Wittich, P.; Wolbers, S.; Wolfe, H.; Wright, T.; Wu, X.; Wu, Z.; Yamamoto, K.; Yamato, D.; Yang, T.; Yang, U. K.; Yang, Y. C.; Yao, W.-M.; Yeh, G. P.; Yi, K.; Yoh, J.; Yorita, K.; Yoshida, T.; Yu, G. B.; Yu, I.; Zanetti, A. M.; Zeng, Y.; Zhou, C.; Zucchelli, S.

2013-08-01

We present the first signature-based search for delayed photons using an exclusive photon plus missing transverse energy final state. Events are reconstructed in a data sample from the CDF II detector corresponding to 6.3fb-1 of integrated luminosity from s=1.96TeV proton-antiproton collisions. Candidate events are selected if they contain a photon with an arrival time in the detector larger than expected from a promptly produced photon. The mean number of events from standard model sources predicted by the data-driven background model based on the photon timing distribution is 286±24. A total of 322 events are observed. A p value of 12% is obtained, showing consistency of the data with standard model predictions.

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

Moon, Chang-Bum, E-mail: cbmoon@hoseo.edu

This paper outlines the new physics possibilities that fall within the field of nuclear structure and astrophysics based on experiments with radioactive ion beams at the future Rare Isotope Beams Accelerator facility in Korea. This ambitious multi-beam facility has both an Isotope Separation On Line (ISOL) and fragmentation capability to produce rare isotopes beams (RIBs) and will be capable of producing and accelerating beams of wide range mass of nuclides with energies of a few to hundreds MeV per nucleon. The large dynamic range of reaccelerated RIBs will allow the optimization in each nuclear reaction case with respect to crossmore » section and channel opening. The low energy RIBs around Coulomb barrier offer nuclear reactions such as elastic resonance scatterings, one or two particle transfers, Coulomb multiple-excitations, fusion-evaporations, and direct capture reactions for the study of the very neutron-rich and proton-rich nuclides. In contrast, the high energy RIBs produced by in-flight fragmentation with reaccelerated ions from the ISOL enable to explore the study of neutron drip lines in intermediate mass regions. The proposed studies aim at investigating the exotic nuclei near and beyond the nucleon drip lines, and to explore how nuclear many-body systems change in such extreme regions by addressing the following topics: the evolution of shell structure in areas of extreme proton to neutron imbalance; the study of the weak interaction in exotic decay schemes such as beta-delayed two-neutron or two-proton emission; the change of isospin symmetry in isobaric mirror nuclei at the drip lines; two protons or two neutrons radioactivity beyond the drip lines; the role of the continuum states including resonant states above the particle-decay threshold in exotic nuclei; and the effects of nuclear reaction rates triggered by the unbound proton-rich nuclei on nuclear astrophysical processes.« less

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

Otto, H.; Marti, T.; Holz, M.

Photocycle and flash-induced proton release and uptake were investigated for bacteriorhodopsin mutants in which Asp-85 was replaced by Ala, Asn, or Glu; Asp-212 was replaced by Asn or Glu; Asp-115 was replaced by Ala, Asn, or Glu; Asp-96 was replaced by Ala, Asn, or Glu; and Arg-82 was replaced by Ala or Gln in dimyristoylphosphatidylcholine/3-((3-cholamidopropyl)dimethylammonio)-1- propanesulfonate micelles at pH 7.3. In the Asp-85----Ala and Asp-85----Asn mutants, the absence of the charged carboxyl group leads to a blue chromophore at 600 and 595 nm, respectively, and lowers the pK of the Schiff base deprotonation to 8.2 and 7, respectively, suggesting amore » role for Asp-85 as counterion to the Schiff base. The early part of the photocycles of the Asp-85----Ala and Asp-85----Asn mutants is strongly perturbed; the formation of a weak M-like intermediate is slowed down about 100-fold over wild type. In both mutants, proton release is also slower but clearly precedes the rise of M. The amplitude of the early reversed photovoltage component in the Asp-85----Asn mutant is very large, and the net charge displacement is close to zero, indicating proton release and uptake on the cytoplasmic side of the membrane. The data suggest an obligatory role for Asp-85 in the efficient deprotonation of the Schiff base and in the proton release phase, probably as proton acceptor. In the Asp-212----Asn mutant, the rise of the absorbance change at 410 nm is slowed down to 220 microsecond, its amplitude is small, and the release of protons is delayed to 1.9 ms. The absorbance changes at 650 nm indicate perturbations in the early time range with a slow K intermediate. Thus Asp-212 also participates in the early events of charge translocation and deprotonation of the Schiff base.« less

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.

The association of spacecraft anomalies with electron/proton particle fluxes at different orbits

NASA Astrophysics Data System (ADS)

Yi, K.; Moon, Y. J.

2016-12-01

In this study, we investigate 195 satellite anomaly data from 1998 to 2010 from Satellite News Digest (SND) to understand the association between spacecraft anomaly and space weather condition. The spacecraft anomalies are classified into Attitude & Propulsion, Power, Control, Telemetry, Instrument and unknown. For the investigation we divide these data according to the spacecraft orbit and launched year. Spacecraft's orbits are classified into the following two groups : (1) high altitude and low inclination, and (2) low altitude and high inclination. Launched year of spacecraft are divided into two groups: 1991 1998 and 1999 2007. We examine the association between these anomaly data and daily peak particle (electron and proton) flux data from GOES as well as their occurrence rates. To determine the association, we use two criteria that electron criterion is >10,000 pfu and proton criterion is >100 pfu. Main results from this study are as follows. First, the number of days satisfying the criteria for electron flux has a peak near a week before the anomaly day and decreases from the peak day to the anomaly day, while that for proton flux has a peak near the anomaly day. Second, we found a similar pattern for the mean daily peak particle (electron and proton) flux as a function of day before the anomaly day. Third, an examination of multiple spacecraft anomaly events, which are likely to occur by severe space weather effects, shows that anomalies mostly occur either when electron fluxes are in the declining stage, or when daily proton peak fluxes are strongly enhanced. Fourth, the time delay between the anomaly day and the day having the highest daily peak electron flux for the recent launching period (1999-2007) is noticeably larger than those for the older periods, implying that the anomaly characteristics associated with electron flux change with time.

MULTI-VIEWPOINT OBSERVATIONS OF A WIDELY DISTRIBUTED SOLAR ENERGETIC PARTICLE EVENT: THE ROLE OF EUV WAVES AND WHITE-LIGHT SHOCK SIGNATURES

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

Kouloumvakos, A.; Patsourakos, S.; Nindos, A.

2016-04-10

On 2012 March 7, two large eruptive events occurred in the same active region within 1 hr from each other. Each consisted of an X-class flare, a coronal mass ejection (CME), an extreme-ultraviolet (EUV) wave, and a shock wave. The eruptions gave rise to a major solar energetic particle (SEP) event observed at widely separated (∼120°) points in the heliosphere. From multi-viewpoint energetic proton recordings we determine the proton release times at STEREO B and A (STB, STA) and the first Lagrange point (L1) of the Sun–Earth system. Using EUV and white-light data, we determine the evolution of the EUVmore » waves in the low corona and reconstruct the global structure and kinematics of the first CME’s shock, respectively. We compare the energetic proton release time at each spacecraft with the EUV waves’ arrival times at the magnetically connected regions and the timing and location of the CME shock. We find that the first flare/CME is responsible for the SEP event at all three locations. The proton release at STB is consistent with arrival of the EUV wave and CME shock at the STB footpoint. The proton release time at L1 was significantly delayed compared to STB. Three-dimensional modeling of the CME shock shows that the particle release at L1 is consistent with the timing and location of the shock’s western flank. This indicates that at L1 the proton release did not occur in low corona but farther away from the Sun. However, the extent of the CME shock fails to explain the SEP event observed at STA. A transport process or a significantly distorted interplanetary magnetic field may be responsible.« less

Improvement of gross theory of beta-decay for application to nuclear data

NASA Astrophysics Data System (ADS)

Koura, Hiroyuki; Yoshida, Tadashi; Tachibana, Takahiro; Chiba, Satoshi

2017-09-01

A theoretical study of β decay and delayed neutron has been carried out with a global β-decay model, the gross theory. The gross theory is based on a consideration of the sum rule of the β-strength function, and gives reasonable results of β-decay rates and delayed neutron in the entire nuclear mass region. In a fissioning nucleus, neutrons are produced by β decay of neutron-rich fission fragments from actinides known as delayed neutrons. The average number of delayed neutrons is estimated based on the sum of the β-delayed neutron-emission probabilities multiplied by the cumulative fission yield for each nucleus. Such a behavior is important to manipulate nuclear reactors, and when we adopt some new high-burn-up reactors, properties of minor actinides will play an important roll in the system, but these data have not been sufficient. We re-analyze and improve the gross theory. For example, we considered the parity of neutrons and protons at the Fermi surface, and treat a suppression for the allowed transitions in the framework of the gross theory. By using the improved gross theory, underestimated half-lives in the neutron-rich indium isotopes and neighboring region increase, and consequently follow experimental trend. The ability of reproduction (and also prediction) of the β-decay rates, delayed-neutron emission probabilities is discussed. With this work, we have described the development of a programming code of the gross theory of β-decay including the improved parts. After preparation finished, this code can be released for the nuclear data community.

D1-Asn-298 in photosystem II is involved in a hydrogen-bond network near the redox-active tyrosine YZ for proton exit during water oxidation.

PubMed

Nagao, Ryo; Ueoka-Nakanishi, Hanayo; Noguchi, Takumi

2017-12-08

In photosynthetic water oxidation, two water molecules are converted into one oxygen molecule and four protons at the Mn 4 CaO 5 cluster in photosystem II (PSII) via the S-state cycle. Efficient proton exit from the catalytic site to the lumen is essential for this process. However, the exit pathways of individual protons through the PSII proteins remain to be identified. In this study, we examined the involvement of a hydrogen-bond network near the redox-active tyrosine Y Z in proton transfer during the S-state cycle. We focused on spectroscopic analyses of a site-directed variant of D1-Asn-298, a residue involved in a hydrogen-bond network near Y Z We found that the D1-N298A mutant of Synechocystis sp. PCC 6803 exhibits an O 2 evolution activity of ∼10% of the wild-type. D1-N298A and the wild-type D1 had very similar features of thermoluminescence glow curves and of an FTIR difference spectrum upon Y Z oxidation, suggesting that the hydrogen-bonded structure of Y Z and electron transfer from the Mn 4 CaO 5 cluster to Y Z were little affected by substitution. In the D1-N298A mutant, however, the flash-number dependence of delayed luminescence showed a monotonic increase without oscillation, and FTIR difference spectra of the S-state cycle indicated partial and significant inhibition of the S 2 → S 3 and S 3 → S 0 transitions, respectively. These results suggest that the D1-N298A substitution inhibits the proton transfer processes in the S 2 → S 3 and S 3 → S 0 transitions. This in turn indicates that the hydrogen-bond network near Y Z can be functional as a proton transfer pathway during photosynthetic water oxidation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Excitation wavelength dependence of excited state intramolecular proton transfer reaction of 4'-N,N-diethylamino-3-hydroxyflavone in room temperature ionic liquids studied by optical Kerr gate fluorescence measurement.

PubMed

Suda, Kayo; Terazima, Masahide; Sato, Hirofumi; Kimura, Yoshifumi

2013-10-17

Excited state intramolecular proton transfer reactions (ESIPT) of 4'-N,N-diethylamino-3-hydroxyflavone (DEAHF) in ionic liquids have been studied by steady-state and time-resolved fluorescence measurements at different excitation wavelengths. Steady-state measurements show the relative yield of the tautomeric form to the normal form of DEAHF decreases as excitation wavelength is increased from 380 to 450 nm. The decrease in yield is significant in ionic liquids that have cations with long alkyl chains. The extent of the decrease is correlated with the number of carbon atoms in the alkyl chains. Time-resolved fluorescence measurements using optical Kerr gate spectroscopy show that ESIPT rate has a strong excitation wavelength dependence. There is a large difference between the spectra at a 200 ps delay from different excitation wavelengths in each ionic liquid. The difference is pronounced in ionic liquids having a long alkyl chain. The equilibrium constant in the electronic excited state obtained at a 200 ps delay and the average reaction rate are also correlated with the alkyl chain length. Considering the results of the steady-state fluorescence and time-resolved measurements, the excitation wavelength dependence of ESIPT is explained by state selective excitation due to the difference of the solvation, and the number of alkyl chain carbon atoms is found to be a good indicator of the effect of inhomogeneity for this reaction.

An optimized small animal tumour model for experimentation with low energy protons.

PubMed

Beyreuther, Elke; Brüchner, Kerstin; Krause, Mechthild; Schmidt, Margret; Szabo, Rita; Pawelke, Jörg

2017-01-01

The long-term aim of developing laser based particle acceleration towards clinical application requires not only substantial technological progress, but also the radiobiological characterization of the resulting ultra-short and ultra-intensive particle beam pulses. After comprehensive cell studies a mouse ear tumour model was established allowing for the penetration of low energy protons (~20 MeV) currently available at laser driven accelerators. The model was successfully applied for a first tumour growth delay study with laser driven electrons, whereby the need of improvements crop out. To optimise the mouse ear tumour model with respect to a stable, high take rate and a lower number of secondary tumours, Matrigel was introduced for tumour cell injection. Different concentrations of two human tumour cell lines (FaDu, LN229) and Matrigel were evaluated for stable tumour growth and fulfilling the allocation criteria for irradiation experiments. The originally applied cell injection with PBS was performed for comparison and to assess the long-term stability of the model. Finally, the optimum suspension of cells and Matrigel was applied to determine applicable dose ranges for tumour growth delay studies by 200 kV X-ray irradiation. Both human tumour models showed a high take rate and exponential tumour growth starting at a volume of ~10 mm3. As disclosed by immunofluorescence analysis these small tumours already interact with the surrounding tissue and activate endothelial cells to form vessels. The formation of delimited, solid tumours at irradiation size was shown by standard H&E staining and a realistic dose range for inducing tumour growth delay without permanent tumour control was obtained for both tumour entities. The already established mouse ear tumour model was successfully upgraded now providing stable tumour growth with high take rate for two tumour entities (HNSCC, glioblastoma) that are of interest for future irradiation experiments at experimental accelerators.

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

Characteristics of gamma-ray line flares

NASA Technical Reports Server (NTRS)

Bai, T.; Dennis, B.

1983-01-01

Observations of solar gamma rays by the Solar Maximum Mission (SMM) demonstrate that energetic protons and ions are rapidly accelerated during the impulsive phase. To understand the acceleration mechanisms for these particles, the characteristics of the gamma ray line flares observed by SMM were studied. Some very intense hard X-ray flares without detectable gamma ray lines were also investigated. Gamma ray line flares are distinguished from other flares by: (1) intense hard X-ray and microwave emissions; (2) delay of high energy hard X-rays; (3) emission of type 2 and/or type 4 radio bursts; and (4) flat hard X-ray spectra (average power law index: 3.1). The majority of the gamma ray line flares shared all these characteristics, and the remainder shared at least three of them. Positive correlations were found between durations of spike bursts and spatial sizes of flare loops as well as between delay times and durations of spike bursts.

Physico-chemical characterization of products from vacuum oil under delayed coking process by infrared spectroscopy and chemometrics methods

NASA Astrophysics Data System (ADS)

Meléndez, L. V.; Cabanzo, R.; Mejía-Ospino, E.; Guzmán, A.

2016-02-01

Eight vacuum residues and their delayed coking liquids products from Colombian crude were study by infrared spectroscopy with attenuated total reflectance (FTIR-ATR) and principal component analysis (PCA). For the samples the structural parameters of aromaticity factor (fa), alifaticity (A2500-3100cm-1), aromatic condensation degree (GCA), length of aliphatic chains (LCA) and aliphatic chain length associated with aromatic (LACAR) were determined through the development of a methodology, which includes the previous processing of spectroscopy data, identifying the regions in the IR spectra of greatest variance using PCA and molecules patterns. The parameters were compared with the results obtained from proton magnetic resonance (1H-NMR) and 13C-NMR. The results showed the influence and correlation of structural parameters with some physicochemical properties such as API gravity, weight percent sulphur (% S) and Conradson carbon content (% CCR)

Simulating the Response of a New Beta Delayed Proton Detector

NASA Astrophysics Data System (ADS)

Roosa, Michael; Friedman, Moshe; Wrede, Christopher

2017-09-01

To better understand reactions of astrophysical importance, such as 15O(α, γ)19Ne and 30P(p, γ)31S, a new gas filled detector of β-delayed charged particles has been designed and built for use at the National Superconducting Cyclotron Laboratory. The detector has separate drift and proportional amplification regions provided by a flex-board field cage and a Micromegas structure, respectively. We have developed a simulation to model the response of this detector using Magboltz and Garfield++ which calculate the electron transport and amplification through the two regions. The simulation provides information that is useful for understanding the microscopic function of the detector and will help optimize its operation. This work is supported by the U.S. National Science Foundation under Award Nos. PHY-1102511 and PHY- 1565546 and the U.S. Department of Energy, Office of Science, under Award No. DE-SC0016052.

Active interrogation using low-energy nuclear reactions

NASA Astrophysics Data System (ADS)

Antolak, Arlyn; Doyle, Barney; Leung, Ka-Ngo; Morse, Daniel; Provencio, Paula

2005-09-01

High-energy photons and neutrons can be used to interrogate for heavily shielded fissile materials inside sealed cargo containers by detecting their prompt and/or delayed fission signatures. The FIND (Fissmat Inspection for Nuclear Detection) active interrogation system is based on a dual neutron+gamma source that uses low-energy (< 500 keV) proton- or deuteron-induced nuclear reactions to produce high intensities of mono-energetic gamma rays and/or neutrons. The source can be operated in either pulsed (e.g., to detect delayed photofission neutrons and gammas) or continuous (e.g., detecting prompt fission signatures) modes. For the gamma-rays, the source target can be segmented to incorporate different (p,γ) isotopes for producing gamma-rays at selective energies, thereby improving the probability of detection. The design parameters for the FIND system are discussed and preliminary accelerator-based measurements of gamma and neutron yields, background levels, and fission signals for several target materials under consideration are presented.

Effect of Boron Clusters on the Ignition Reaction of HNO3 and Dicynanamide-Based Ionic Liquids.

PubMed

Schmidt, Michael W; Gordon, Mark S

2017-10-19

Many ionic liquids containing the dicynamide anion (DCA - , formula N(CN) 2 - ) exhibit hypergolic ignition when exposed to the common oxidizer nitric acid. However, the ignition delay is often about 10 times longer than the desired 5 ms for rocket applications, so that improvements are desired. Experiments in the past decade have suggested both a mechanism for the early reaction steps and also that additives such as decaborane can reduce the ignition delay. The mechanisms for reactions of nitric acid with both DCA - and protonated DCAH are considered here, using accurate wave function methods. Complexation of DCA - or DCAH with borane clusters B 10 H 14 or B 9 H 14 - is found to modify these mechanisms slightly by changing the nature of some of the intermediate saddle points and by small reductions in the reaction barriers.

High-energy proton irradiation of C57Bl6 mice under hindlimb unloading

NASA Astrophysics Data System (ADS)

Mendonca, Marc; Todd, Paul; Orschell, Christie; Chin-Sinex, Helen; Farr, Jonathan; Klein, Susan; Sokol, Paul

2012-07-01

Solar proton events (SPEs) pose substantial risk for crewmembers on deep space missions. It has been shown that low gravity and ionizing radiation both produce transient anemia and immunodeficiencies. We utilized the C57Bl/6 based hindlimb suspension model to investigate the consequences of hindlimb-unloading induced immune suppression on the sensitivity to whole body irradiation with modulated 208 MeV protons. Eight-week old C57Bl/6 female mice were conditioned by hindlimb-unloading. Serial CBC and hematocrit assays by HEMAVET were accumulated for the hindlimb-unloaded mice and parallel control animals subjected to identical conditions without unloading. One week of hindlimb-unloading resulted in a persistent, statistically significant 10% reduction in RBC count and a persistent, statistically significant 35% drop in lymphocyte count. This inhibition is consistent with published observations of low Earth orbit flown mice and with crewmember blood analyses. In our experiments the cell count suppression was sustained for the entire six-week period of observation and persisted for at least 7 days beyond the period of active hindlimb-unloading. C57Bl/6 mice were also irradiated with 208 MeV Spread Out Bragg Peak (SOBP) protons at the Midwest Proton Radiotherapy Institute at the Indiana University Cyclotron Facility. We found that at 8.5 Gy hindlimb-unloaded mice were significantly more radiation sensitive with 35 lethalities out of 51 mice versus 15 out of 45 control (non-suspended) mice within 30 days of receiving 8.5 Gy of SOBP protons (p =0.001). Both control and hindlimb-unloaded stocktickerCBC analyses of 8.5 Gy proton irradiated and control mice by HEMAVET demonstrated severe reductions in WBC counts (Lymphocytes and PMNs) by day 2 post-irradiation, followed a week to ten days later by reductions in platelets, and then reductions in RBCs about 2 weeks post-irradiation. Recovery of all blood components commenced by three weeks post-irradiation. CBC analyses of 8.5 Gy proton irradiated hindlimb-unloaded mice indicated that the recovery of the WBC counts appeared delayed compared to 8.5 Gy irradiated controls. However, stocktickerRBC recovery appeared similar in both sets of irradiated mice. Our data indicate that hindlimb-unloaded mice are more radiation sensitive compared to irradiated controls. We thank Brian Allen and Rick Jessup for valuable assistance with dosimetry and physical arrangements at the IU Cyclotron Facility and Midwest Proton Radiotherapy Institute and Alan Constance for design of hindlimb-unloading cages. Research supported in part by NASA Grant NNJ06HE95A.

Evaluating the potential impact of proton carriers on syntrophic propionate oxidation

NASA Astrophysics Data System (ADS)

Juste-Poinapen, Natacha M. S.; Turner, Mark S.; Rabaey, Korneel; Virdis, Bernardino; Batstone, Damien J.

2015-12-01

Anaerobic propionic acid degradation relies on interspecies electron transfer (IET) between propionate oxidisers and electron acceptor microorganisms, via either molecular hydrogen, formate or direct transfers. We evaluated the possibility of stimulating direct IET, hence enhancing propionate oxidation, by increasing availability of proton carriers to decrease solution resistance and reduce pH gradients. Phosphate was used as a proton carrying anion, and chloride as control ion together with potassium as counter ion. Propionic acid consumption in anaerobic granules was assessed in a square factorial design with ratios (1:0, 2:1, 1:1, 1:2 and 0:1) of total phosphate (TP) to Cl-, at 1X, 10X, and 30X native conductivity (1.5 mS.cm-1). Maximum specific uptake rate, half saturation, and time delay were estimated using model-based analysis. Community profiles were analysed by fluorescent in situ hybridisation and 16S rRNA gene pyrosequencing. The strongest performance was at balanced (1:1) ratios at 10X conductivity where presumptive propionate oxidisers namely Syntrophobacter and Candidatus Cloacamonas were more abundant. There was a shift from Methanobacteriales at high phosphate, to Methanosaeta at low TP:Cl ratios and low conductivity. A lack of response to TP, and low percentage of presumptive electroactive organisms suggested that DIET was not favoured under the current experimental conditions.

Effects of Gas-Wall Partitioning in Teflon Tubing, Instrumentation and Other Materials on Time-Resolved Measurements of Gas-Phase Organic Compounds

NASA Astrophysics Data System (ADS)

Pagonis, D.; Deming, B.; Krechmer, J. E.; De Gouw, J. A.; Jimenez, J. L.; Ziemann, P. J.

2017-12-01

Recently it has been shown that gas-phase organic compounds partition to and from the walls of Teflon environmental chambers. This process is fast, reversible, and can be modeled as absorptive partitioning. Here these studies were extended to investigate gas-wall partitioning inside Teflon tubing by introducing step function changes in the concentration of compounds being sampled and measuring the delay in the response of a proton transfer reaction-mass spectrometer (PTR-MS). We find that these delays are significant for compounds with a saturation vapor concentration (c*) below 106 μg m-3, and that the Teflon tubing and the PTR-MS both contribute to the delays. Tubing delays range from minutes to hours under common sampling conditions and can be accurately predicted by a simple chromatography model across a range of tubing lengths and diameters, flow rates, compound functional groups, and c*. This method also allows one to determine the volatility-dependent response function of an instrument, which can be convolved with the output of the tubing model to correct for delays in instrument response time for these "sticky" compounds. This correction is expected to be of particular interest to researchers utilizing and developing chemical ionization mass spectrometry (CIMS) techniques, since many of the multifunctional organic compounds detected by CIMS show significant tubing and instrument delays. These results also enable better design of sampling systems, in particular when fast instrument response is needed, such as for rapid transients, aircraft, or eddy covariance measurements. Additional results presented here extend this method to quantify the relative sorptive capacities for other commonly used tubing materials, including PFA, FEP, PTFE, PEEK, glass, copper, stainless steel, and passivated steel.

Pantoprazole: a new proton pump inhibitor.

PubMed

Jungnickel, P W

2000-11-01

This paper reviews the pharmacology, clinical efficacy, and tolerability of pantoprazole in comparison with those of other available proton pump inhibitors (PPIs). Relevant English-language research and review articles were identified by database searches of MEDLINE, International Pharmaceutical Abstracts, and UnCover, and by examining the reference lists of the articles so identified. In selecting data for inclusion, the author gave preference to full-length articles published in peer-reviewed journals. Like other PPIs, pantoprazole exerts its pharmacodynamic actions by binding to the proton pump (H+,K+ -adenosine triphosphatase) in the parietal cells, but, compared with other PPIs, its binding may be more specific for the proton pump. Pantoprazole is well absorbed when administered as an enteric-coated, delayed-release tablet, with an oral bioavailability of approximately 77%. It is hepatically metabolized via cytochrome P2C19 to hydroxypantoprazole, an inactive metabolite that subsequently undergoes sulfate conjugation. The elimination half-life ranges from 0.9 to 1.9 hours and is independent of dose. Pantoprazole has similar efficacy to other PPIs in the healing of gastric and duodenal ulcers, as well as erosive esophagitis, and as part of triple-drug regimens for the eradication of Helicobacter pylori from the gastric mucosa. It is well tolerated, with the most common adverse effects being headache, diarrhea, flatulence, and abdominal pain. In clinical studies, it has been shown to have no interactions with various other agents, including carbamazepine, cisapride, cyclosporine, digoxin, phenytoin, theophylline, and warfarin. Pantoprazole appears to be as effective as other PPIs. Its low potential for drug interactions may give it an advantage in patients taking other drugs.

Solar energetic particles and space weather

NASA Astrophysics Data System (ADS)

Reames, Donald V.; Tylka, Allan J.; Ng, Chee K.

2001-02-01

The solar energetic particles (SEPs) of consequence to space weather are accelerated at shock waves driven out from the Sun by fast coronal mass ejections (CMEs). In the large events, these great shocks fill half of the heliosphere. SEP intensity profiles change appearance with longitude. Events with significant intensities of >10 MeV protons occur at an average rate of ~13 yr-1 near solar maximum and several events with high intensities of >100 MeV protons occur each decade. As particles stream out along magnetic field lines from a shock near the Sun, they generate waves that scatter subsequent particles. At high intensities, wave growth throttles the flow below the ``streaming limit.'' However, if the shock maintains its strength, particle intensities can rise above this limit to a peak when the shock itself passes over the observer creating a `delayed' radiation hazard, even for protons with energies up to ~1 GeV. The streaming limit makes us blind to the intensities at the oncoming shock, however, heavier elements such as He, O, and Fe probe the shape of the wave spectrum, and variation in abundances of these elements allow us to evade the limit and probe conditions at the shock, with the aid of detailed modeling. At high energies, spectra steepen to form a spectral `knee.' The location of the proton spectral knee can vary from ~10 MeV to ~1 GeV, depending on shock conditions, greatly affecting the radiation hazard. Hard spectra are a serious threat to astronauts, placing challenging requirements for shielding, especially on long-duration missions to the moon or Mars. .

Solar Energetic Particles and Space Weather

NASA Technical Reports Server (NTRS)

Reames, Donald V.; Tylka, Allan J.; Ng, Chee K.

2001-01-01

The solar energetic particles (SEPs) of consequence to space weather are accelerated at shock waves driven out from the Sun by fast coronal mass ejections (CMEs). In the large events, these great shocks fill half of the heliosphere. SEP intensity profiles change appearance with longitude. Events with significant intensities of greater than ten MeV protons occur at an average rate of approx. 13 per year near solar maximum and several events with high intensities of > 100 McV protons occur each decade. As particles stream out along magnetic field lines from a shock near the Sun, they generate waves that scatter subsequent particles. At high intensities, wave growth throttles the flow below the 'streaming limit.' However, if the shock maintains its strength, particle intensities can rise above this limit to a peak when the shock itself passes over the observer creating a 'delayed' radiation hazard, even for protons with energies up to approx. one GeV. The streaming limit makes us blind to the intensities at the oncoming shock, however, heavier elements such as He, O, and Fe probe the shape of the wave spectrum, and variation in abundances of these elements allow us to evade the limit and probe conditions at the shock, with the aid of detailed modeling. At high energies, spectra steepen to form a spectral 'knee'. The location of the proton spectral knee can vary from approx. ten MeV to approx. one GeV, depending on shock conditions, greatly affecting the radiation hazard. Hard spectra are a serious threat to astronauts, placing challenging requirements for shielding, especially on long-duration missions to the moon or Mars.

New portal to the 15O(α ,γ )19Ne resonance triggering CNO-cycle breakout

NASA Astrophysics Data System (ADS)

Wrede, C.; Glassman, B. E.; Pérez-Loureiro, D.; Allen, J. M.; Bardayan, D. W.; Bennett, M. B.; Brown, B. A.; Chipps, K. A.; Febbraro, M.; Fry, C.; Hall, M. R.; Hall, O.; Liddick, S. N.; O'Malley, P.; Ong, W.-J.; Pain, S. D.; Schwartz, S. B.; Shidling, P.; Sims, H.; Thompson, P.; Zhang, H.

2017-09-01

The 15O(α ,γ )19Ne reaction is expected to trigger the initial path for breakout from the CNO hydrogen-burning cycles to the rapid proton capture (r p ) process in type I x-ray bursts on accreting neutron stars. The thermonuclear reaction rate has a major impact on models of type I x-ray burst observables and it depends on the small α -particle branching ratio, Γα/Γ , of the 4.03 MeV state in 19Ne. Attempts to measure Γα/Γ by populating the 4.03 MeV state using nuclear reactions have only led to strong upper limits. In the present work, we report the first experimental evidence that the 4.03 MeV 19Ne state is populated in 20Mg β -delayed proton emission. This new channel has the potential to provide the necessary sensitivity to detect a finite value of Γα/Γ .

De novo mutations of the ATP6V1A gene cause developmental encephalopathy with epilepsy.

PubMed

Fassio, Anna; Esposito, Alessandro; Kato, Mitsuhiro; Saitsu, Hirotomo; Mei, Davide; Marini, Carla; Conti, Valerio; Nakashima, Mitsuko; Okamoto, Nobuhiko; Olmez Turker, Akgun; Albuz, Burcu; Semerci Gündüz, C Nur; Yanagihara, Keiko; Belmonte, Elisa; Maragliano, Luca; Ramsey, Keri; Balak, Chris; Siniard, Ashley; Narayanan, Vinodh; Ohba, Chihiro; Shiina, Masaaki; Ogata, Kazuhiro; Matsumoto, Naomichi; Benfenati, Fabio; Guerrini, Renzo

2018-06-01

V-type proton (H+) ATPase (v-ATPase) is a multi-subunit proton pump that regulates pH homeostasis in all eukaryotic cells; in neurons, v-ATPase plays additional and unique roles in synapse function. Through whole exome sequencing, we identified de novo heterozygous mutations (p.Pro27Arg, p.Asp100Tyr, p.Asp349Asn, p.Asp371Gly) in ATP6V1A, encoding the A subunit of v-ATPase, in four patients with developmental encephalopathy with epilepsy. Early manifestations, observed in all patients, were developmental delay and febrile seizures, evolving to encephalopathy with profound delay, hypotonic/dyskinetic quadriparesis and intractable multiple seizure types in two patients (p.Pro27Arg, p.Asp100Tyr), and to moderate delay with milder epilepsy in the other two (p.Asp349Asn, p.Asp371Gly). Modelling performed on the available prokaryotic and eukaryotic structures of v-ATPase predicted p.Pro27Arg to perturb subunit interaction, p.Asp100Tyr to cause steric hindrance and destabilize protein folding, p.Asp349Asn to affect the catalytic function and p.Asp371Gly to impair the rotation process, necessary for proton transport. We addressed the impact of p.Asp349Asn and p.Asp100Tyr mutations on ATP6V1A expression and function by analysing ATP6V1A-overexpressing HEK293T cells and patients' lymphoblasts. The p.Asp100Tyr mutant was characterized by reduced expression due to increased degradation. Conversely, no decrease in expression and clearance was observed for p.Asp349Asn. In HEK293T cells overexpressing either pathogenic or control variants, p.Asp349Asn significantly increased LysoTracker® fluorescence with no effects on EEA1 and LAMP1 expression. Conversely, p.Asp100Tyr decreased both LysoTracker® fluorescence and LAMP1 levels, leaving EEA1 expression unaffected. Both mutations decreased v-ATPase recruitment to autophagosomes, with no major impact on autophagy. Experiments performed on patients' lymphoblasts using the LysoSensor™ probe revealed lower pH of endocytic organelles for p.Asp349Asn and a reduced expression of LAMP1 with no effect on the pH for p.Asp100Tyr. These data demonstrate gain of function for p.Asp349Asn characterized by an increased proton pumping in intracellular organelles, and loss of function for p.Asp100Tyr with decreased expression of ATP6V1A and reduced levels of lysosomal markers. We expressed p.Asp349Asn and p.Asp100Tyr in rat hippocampal neurons and confirmed significant and opposite effects in lysosomal labelling. However, both mutations caused a similar defect in neurite elongation accompanied by loss of excitatory inputs, revealing that altered lysosomal homeostasis markedly affects neurite development and synaptic connectivity. This study provides evidence that de novo heterozygous ATP6V1A mutations cause a developmental encephalopathy with a pathomechanism that involves perturbations of lysosomal homeostasis and neuronal connectivity, uncovering a novel role for v-ATPase in neuronal development.

Impact of uneven sample morphology on mass resolving power in linear MALDI-TOF mass spectrometry: A comprehensive theoretical investigation.

PubMed

Cai, Yi-Hong; Wang, Yi-Sheng

2018-04-01

This work discusses the correlation between the mass resolving power of matrix-assisted laser desorption/ionization time-of-flight mass analyzers and extraction condition with an uneven sample morphology. Previous theoretical calculations show that the optimum extraction condition for flat samples involves an ideal ion source design and extraction delay. A general expression of spectral feature takes into account ion initial velocity, and extraction delay is derived in the current study. The new expression extends the comprehensive calculation to uneven sample surfaces and above 90% Maxell-Boltzmann initial velocity distribution of ions to account for imperfect ionization condition. Calculation shows that the impact of uneven sample surface or initial spatial spread of ions is negligible when the extraction delay is away from the ideal value. When the extraction delay approaches the optimum value, the flight-time topology shows a characteristic curve shape, and the time-domain mass spectral feature broadens with an increase in initial spatial spread of ions. For protonated 2,5-dihydroxybenzoic acid, the mass resolving power obtained from a sample of 3-μm surface roughness is approximately 3.3 times lower than that of flat samples. For ions of m/z 3000 coexpanded with 2,5-dihydroxybenzoic acid, the mass resolving power in the 3-μm surface roughness case only reduces roughly 7%. Comprehensive calculations also show that the mass resolving power of lighter ions is more sensitive to the accuracy of the extraction delay than heavier ions. Copyright © 2018 John Wiley & Sons, Ltd.

Comparison of two methods for minimizing the effect of delayed charge on the dose delivered with a synchrotron based discrete spot scanning proton beam.

PubMed

Whitaker, Thomas J; Beltran, Chris; Tryggestad, Erik; Bues, Martin; Kruse, Jon J; Remmes, Nicholas B; Tasson, Alexandria; Herman, Michael G

2014-08-01

Delayed charge is a small amount of charge that is delivered to the patient after the planned irradiation is halted, which may degrade the quality of the treatment by delivering unwarranted dose to the patient. This study compares two methods for minimizing the effect of delayed charge on the dose delivered with a synchrotron based discrete spot scanning proton beam. The delivery of several treatment plans was simulated by applying a normally distributed value of delayed charge, with a mean of 0.001(SD 0.00025) MU, to each spot. Two correction methods were used to account for the delayed charge. Method one (CM1), which is in active clinical use, accounts for the delayed charge by adjusting the MU of the current spot based on the cumulative MU. Method two (CM2) in addition reduces the planned MU by a predicted value. Every fraction of a treatment was simulated using each method and then recomputed in the treatment planning system. The dose difference between the original plan and the sum of the simulated fractions was evaluated. Both methods were tested in a water phantom with a single beam and simple target geometry. Two separate phantom tests were performed. In one test the dose per fraction was varied from 0.5 to 2 Gy using 25 fractions per plan. In the other test the number fractions were varied from 1 to 25, using 2 Gy per fraction. Three patient plans were used to determine the effect of delayed charge on the delivered dose under realistic clinical conditions. The order of spot delivery using CM1 was investigated by randomly selecting the starting spot for each layer, and by alternating per layer the starting spot from first to last. Only discrete spot scanning was considered in this study. Using the phantom setup and varying the dose per fraction, the maximum dose difference for each plan of 25 fractions was 0.37-0.39 Gy and 0.03-0.05 Gy for CM1 and CM2, respectively. While varying the total number of fractions, the maximum dose difference increased at a rate of 0.015 Gy and 0.0018 Gy per fraction for CM1 and CM2, respectively. For CM1, the largest dose difference was found at the location of the first spot in each energy layer, whereas for CM2 the difference in dose was small and showed no dependence on location. For CM1, all of the fields in the patient plans had an area where their excess dose overlapped. No such correlation was found when using CM2. Randomly selecting the starting spot reduces the maximum dose difference from 0.708 to 0.15 Gy. Alternating between first and last spot reduces the maximum dose difference from 0.708 to 0.37 Gy. In the patient plans the excess dose scaled linearly at 0.014 Gy per field per fraction for CM1 and standard delivery order. The predictive model CM2 is superior to a cumulative irradiation model CM1 for minimizing the effects of delayed charge, particularly when considering maximal dose discrepancies and the potential for unplanned hot-spots. This study shows that the dose discrepancy potentially scales at 0.014 Gy per field per fraction for CM1.

Arabidopsis plants harbouring a mutation in AtSUC2, encoding the predominant sucrose/proton symporter necessary for efficient phloem transport, are able to complete their life cycle and produce viable seed

PubMed Central

Srivastava, Avinash C.; Dasgupta, Kasturi; Ajieren, Eric; Costilla, Gabriella; McGarry, Roisin C.; Ayre, Brian G.

2009-01-01

Background and Aims AtSUC2 encodes a sucrose/proton symporter that localizes throughout the collection and transport phloem and is necessary for efficient transport of sucrose from source to sink tissues in Arabidopsis thaliana. Plants harbouring homozygous AtSUC2 null alleles accumulate sugar, starch, and anthocyanin in mature leaves, have severely delayed development and stunted growth and, in previous studies, failed to complete their life cycle by producing viable seed. Methods An AtSUC2 allele with a T-DNA insertion in the second intron was analysed. Full-length transcript from this allele is not produced, and a truncated protein translated from sequences upstream of the insertion site did not catalyse sucrose uptake into yeast, supporting the contention that this is a null allele. Mutant plants were grown in a growth chamber with a diurnal light/dark cycle, and growth patterns recorded. Key Results This allele (SALK_038124, designated AtSUC2-4) has the hallmarks of previously described null alleles but, despite compromised carbon partitioning and growth, produces viable seeds. The onset of flowering was chronologically delayed but occurred at the same point in the plastochron index as wild type. Conclusions AtSUC2 is important for phloem loading and is therefore fundamental to phloem transport and plant productivity, but plants can complete their life cycle and produce viable seed in its absence. Arabidopsis appears to have mechanisms for mobilizing reduced carbon from the phloem into developing seeds independent of AtSUC2. PMID:19789176

Decay studies of neutron deficient nuclei near the Z=64 subshell: 142Dy, 140,142Tb, 140,142Gd, 140,142Eu, 142Sm, and 142Pm

NASA Astrophysics Data System (ADS)

Firestone, R. B.; Gilat, J.; Nitschke, J. M.; Wilmarth, P. A.; Vierinen, K. S.

1991-03-01

The electron-capture and β+-decay branchings (EC/β+) and delayed proton decays of A=142 isotopes with 61<=Z<=66 and A=140 isotopes with 63<=Z<=65 were investigated with the OASIS facility on-line at the Lawrence Berkeley Laboratory SuperHILAC. Electron capture and positron-decay emission probabilities have been determined for 142Pm and 142Sm decays, and extensive decay schemes have been constructed for 142Eug(2.34+/-0.12 s), 142Gd(70.2+/-0.6 s), 140Eu(1.51+/-0.02 s), and 140Gd(15.8+/-0.4 s). Decay schemes for the new isotopes 142Tbg(597+/-17 ms), 142Tbm(303+/-17 ms), 142Dy(2.3+/-0.3 s), 140Eum(125+/-2 ms), and 140Tb(2.4+/-0.2 s) are also presented. We have assigned γ rays to these isotopes on the basis of γγ and xγ coincidences, and from half-life determinations. Electron-capture and β+-decay branchings were measured for each decay, and β-delayed proton branchings were determined for 142Dy, 142Tb, and 140Tb decays. QEC values, derived from the measured EC/β+ branchings and the level schemes are compared with those from the Wapstra and Audi mass evaluation and the Liran and Zeldes mass calculation. The systematics of the N=77 isomer decays are discussed, and the intense 0+-->1+ and 1+-->0+ ground-state beta decays are compared with shell-model predictions for simple spin-flip transitions.

Arabidopsis plants harbouring a mutation in AtSUC2, encoding the predominant sucrose/proton symporter necessary for efficient phloem transport, are able to complete their life cycle and produce viable seed.

PubMed

Srivastava, Avinash C; Dasgupta, Kasturi; Ajieren, Eric; Costilla, Gabriella; McGarry, Roisin C; Ayre, Brian G

2009-11-01

AtSUC2 encodes a sucrose/proton symporter that localizes throughout the collection and transport phloem and is necessary for efficient transport of sucrose from source to sink tissues in Arabidopsis thaliana. Plants harbouring homozygous AtSUC2 null alleles accumulate sugar, starch, and anthocyanin in mature leaves, have severely delayed development and stunted growth and, in previous studies, failed to complete their life cycle by producing viable seed. An AtSUC2 allele with a T-DNA insertion in the second intron was analysed. Full-length transcript from this allele is not produced, and a truncated protein translated from sequences upstream of the insertion site did not catalyse sucrose uptake into yeast, supporting the contention that this is a null allele. Mutant plants were grown in a growth chamber with a diurnal light/dark cycle, and growth patterns recorded. This allele (SALK_038124, designated AtSUC2-4) has the hallmarks of previously described null alleles but, despite compromised carbon partitioning and growth, produces viable seeds. The onset of flowering was chronologically delayed but occurred at the same point in the plastochron index as wild type. AtSUC2 is important for phloem loading and is therefore fundamental to phloem transport and plant productivity, but plants can complete their life cycle and produce viable seed in its absence. Arabidopsis appears to have mechanisms for mobilizing reduced carbon from the phloem into developing seeds independent of AtSUC2.

Improving the resolution in proton-detected through-space heteronuclear multiple quantum correlation NMR spectroscopy.

PubMed

Shen, Ming; Trébosc, J; Lafon, O; Pourpoint, F; Hu, Bingwen; Chen, Qun; Amoureux, J-P

2014-08-01

Connectivities and proximities between protons and low-gamma nuclei can be probed in solid-state NMR spectroscopy using two-dimensional (2D) proton-detected heteronuclear correlation, through Heteronuclear Multiple Quantum Correlation (HMQC) pulse sequence. The indirect detection via protons dramatically enhances the sensitivity. However, the spectra are often broadened along the indirect F1 dimension by the decay of heteronuclear multiple-quantum coherences under the strong (1)H-(1)H dipolar couplings. This work presents a systematic comparison of the performances of various decoupling schemes during the indirect t1 evolution period of dipolar-mediated HMQC (D-HMQC) experiment. We demonstrate that (1)H-(1)H dipolar decoupling sequences during t1, such as symmetry-based schemes, phase-modulated Lee-Goldburg (PMLG) and Decoupling Using Mind-Boggling Optimization (DUMBO), provide better resolution than continuous wave (1)H irradiation. We also report that high resolution requires the preservation of (1)H isotropic chemical shifts during the decoupling sequences. When observing indirectly broad spectra presenting numerous spinning sidebands, the D-HMQC sequence must be fully rotor-synchronized owing to the rotor-synchronized indirect sampling and dipolar recoupling sequence employed. In this case, we propose a solution to reduce artefact sidebands caused by the modulation of window delays before and after the decoupling application during the t1 period. Moreover, we show that (1)H-(1)H dipolar decoupling sequence using Smooth Amplitude Modulation (SAM) minimizes the t1-noise. The performances of the various decoupling schemes are assessed via numerical simulations and compared to 2D (1)H-{(13)C} D-HMQC experiments on [U-(13)C]-L-histidine⋅HCl⋅H2O at various magnetic fields and Magic Angle spinning (MAS) frequencies. Great resolution and sensitivity enhancements resulting from decoupling during t1 period enable the detection of heteronuclear correlation between aliphatic protons and ammonium (14)N sites in L-histidine⋅HCl⋅H2O. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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

Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable radiosensitizers

PubMed Central

Cho, Jongmin; Wang, Min; Gonzalez-Lepera, Carlos; Mawlawi, Osama; Cho, Sang Hyun

2016-01-01

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 to 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 66Ga 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 × 106 counts) with several other peaks of smaller magnitude for each proton energy sample. PET imaging showed strong PET signals from mostly decaying 66Ga. 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. PMID:27487895

Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable radiosensitizers.

PubMed

Cho, Jongmin; Wang, Min; Gonzalez-Lepera, Carlos; Mawlawi, Osama; Cho, Sang Hyun

2016-08-01

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. Nearly spherical zinc NPs (∼5-nm diameter) were synthesized and then coated with a ∼4.25-nm gold layer to 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. The authors measured 168 μCi of activity 32 min after the end of bombardment for the 14.15-MeV proton energy sample using the (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(6) counts) with several other peaks of smaller magnitude for each proton energy sample. PET imaging showed strong PET signals from mostly decaying (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. 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.

Substitution of amino acids Asp-85, Asp-212, and Arg-82 in bacteriorhodopsin affects the proton release phase of the pump and the pK of the Schiff base.

PubMed

Otto, H; Marti, T; Holz, M; Mogi, T; Stern, L J; Engel, F; Khorana, H G; Heyn, M P

1990-02-01

Photocycle and flash-induced proton release and uptake were investigated for bacteriorhodopsin mutants in which Asp-85 was replaced by Ala, Asn, or Glu; Asp-212 was replaced by Asn or Glu; Asp-115 was replaced by Ala, Asn, or Glu; Asp-96 was replaced by Ala, Asn, or Glu; and Arg-82 was replaced by Ala or Gln in dimyristoylphosphatidylcholine/3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonate micelles at pH 7.3. In the Asp-85----Ala and Asp-85----Asn mutants, the absence of the charged carboxyl group leads to a blue chromophore at 600 and 595 nm, respectively, and lowers the pK of the Schiff base deprotonation to 8.2 and 7, respectively, suggesting a role for Asp-85 as counterion to the Schiff base. The early part of the photocycles of the Asp-85----Ala and Asp-85----Asn mutants is strongly perturbed; the formation of a weak M-like intermediate is slowed down about 100-fold over wild type. In both mutants, proton release is also slower but clearly precedes the rise of M. The amplitude of the early (less than 0.2 microseconds) reversed photovoltage component in the Asp-85----Asn mutant is very large, and the net charge displacement is close to zero, indicating proton release and uptake on the cytoplasmic side of the membrane. The data suggest an obligatory role for Asp-85 in the efficient deprotonation of the Schiff base and in the proton release phase, probably as proton acceptor. In the Asp-212----Asn mutant, the rise of the absorbance change at 410 nm is slowed down to 220 microsecond, its amplitude is small, and the release of protons is delayed to 1.9 ms. The absorbance changes at 650 nm indicate perturbations in the early time range with a slow K intermediate. Thus Asp-212 also participates in the early events of charge translocation and deprotonation of the Schiff base. In the Arg-82----Gln mutant, no net transient proton release was observed, whereas, in the Arg-82----Ala mutant, uptake and release were reversed. The pK shift of the purple-to-blue transition in the Asp-85----Glu, Arg-82----Ala, and Arg-82----Gln mutants and the similarity in the photocycle and photoelectrical signals of the Asp-85----Ala, Asp-85----Asn, and Asp-212----Asn mutants suggest the interaction between Asp-85, Arg-82, Asp-212, and the Schiff base as essential for proton release.

Evaluating the potential impact of proton carriers on syntrophic propionate oxidation

PubMed Central

Juste-Poinapen, Natacha M. S.; Turner, Mark S.; Rabaey, Korneel; Virdis, Bernardino; Batstone, Damien J.

2015-01-01

Anaerobic propionic acid degradation relies on interspecies electron transfer (IET) between propionate oxidisers and electron acceptor microorganisms, via either molecular hydrogen, formate or direct transfers. We evaluated the possibility of stimulating direct IET, hence enhancing propionate oxidation, by increasing availability of proton carriers to decrease solution resistance and reduce pH gradients. Phosphate was used as a proton carrying anion, and chloride as control ion together with potassium as counter ion. Propionic acid consumption in anaerobic granules was assessed in a square factorial design with ratios (1:0, 2:1, 1:1, 1:2 and 0:1) of total phosphate (TP) to Cl−, at 1X, 10X, and 30X native conductivity (1.5 mS.cm−1). Maximum specific uptake rate, half saturation, and time delay were estimated using model-based analysis. Community profiles were analysed by fluorescent in situ hybridisation and 16S rRNA gene pyrosequencing. The strongest performance was at balanced (1:1) ratios at 10X conductivity where presumptive propionate oxidisers namely Syntrophobacter and Candidatus Cloacamonas were more abundant. There was a shift from Methanobacteriales at high phosphate, to Methanosaeta at low TP:Cl ratios and low conductivity. A lack of response to TP, and low percentage of presumptive electroactive organisms suggested that DIET was not favoured under the current experimental conditions. PMID:26670292

Magnetization transfer contrast-suppressed imaging of amide proton transfer and relayed nuclear overhauser enhancement chemical exchange saturation transfer effects in the human brain at 7T.

PubMed

Xu, Xiang; Yadav, Nirbhay N; Zeng, Haifeng; Jones, Craig K; Zhou, Jinyuan; van Zijl, Peter C M; Xu, Jiadi

2016-01-01

To use the variable delay multipulse (VDMP) chemical exchange saturation transfer (CEST) approach to obtain clean amide proton transfer (APT) and relayed Nuclear Overhauser enhancement (rNOE) CEST images in the human brain by suppressing the conventional magnetization transfer contrast (MTC) and reducing the direct water saturation contribution. The VDMP CEST scheme consists of a train of RF pulses with a specific mixing time. The CEST signal with respect to the mixing time shows distinguishable characteristics for protons with different exchange rates. Exchange rate filtered CEST images are generated by subtracting images acquired at two mixing times at which the MTC signals are equal, while the APT and rNOE-CEST signals differ. Because the subtraction is performed at the same frequency offset for each voxel and the CEST signals are broad, no B0 correction is needed. MTC-suppressed APT and rNOE-CEST images of human brain were obtained using the VDMP method. The APT-CEST data show hyperintensity in gray matter versus white matter, whereas the rNOE-CEST images show negligible contrast between gray and white matter. The VDMP approach provides a simple and rapid way of recording MTC-suppressed APT-CEST and rNOE-CEST images without the need for B0 field correction. © 2015 Wiley Periodicals, Inc.

Probing of high density plasmas using the multi-beam, high power TiSa laser system ARCTURUS

NASA Astrophysics Data System (ADS)

Willi, Oswald; Aktan, Esin; Brauckmann, Stephannie; Aurand, Bastian; Cerchez, Mirela; Prasad, Rajendra; Schroer, Anna Marie

2017-10-01

The understanding of relativistic laser plasma interaction at ultra-high intensities has advanced considerably during the last decade with the availability of multi-beam, high power TiSa laser systems. These laser systems allow pump-probe experiments to be carried out. The ARCTURUS laser at the University of Duesseldorf is ideally suited for various kinds of pump-probe experiments as it consists of two identical, high power beams with energies of 5J in 30 fs and a third beam for optical probing with energy of 30mJ in a 30fs pulse. All three beams are synchronised and have flexible time delays with respect to each other. Several different processes were studied where one of the beams was used as an interaction beam and the second one was incident on a thin solid gold foil to generate a proton beam. For example, thin foil targets were irradiated either with a linear or circular polarized pulse and probed with protons at different times. The expansion of foils for the two cases was clearly different consistent with numerical simulations. In addition, the interaction of gas targets was probed with protons and separately with an optical probe. With both diagnostics the formation of a channel was observed. In the presentation various two beam measurements will be discussed.

Delayed Effects of Proton Irradiation in Macaca Mulatta. II. Mortality (15-Year Report).

DTIC Science & Technology

1983-01-01

Fig. 9) had significantly (p=.lO) earlier deaths in the combined sexes and the females. In these cases, death rates increased at -2 and -6 years post...while significance occurred in only the combined sexes (p<.lO). All 32-MeV males are alive. This fact increases the ability to detect higher death rates in...where the 55-MeV death rate exceeded the 32-MeV death rate after 4 years. Figures 12 and 13 indicate higher death rates in 138- and 400-MeV males (p<.lO

Shielding activated return water at the ESS

NASA Astrophysics Data System (ADS)

Klinkby, Esben; Muhrer, Günter; Carlsson, H.; Eriksson, Björn

2018-06-01

ESS utilises water both for moderating neutrons to thermal energies, as well as to cool beryllium- and steel reflectors, the shielding and plugs. This means that the water, in separate loops, will be subject to a significant proton and neutron irradiation causing the water to activate. After irradiation, the water is led to delay tanks situated inside the target building. Before returned to the target monolith ∼ 10% is led to the ion exchanger. This paper aims at determining the shielding required to ensure that the biological dose-rate requirements in the target building and neighbouring instrument halls are met during operation of facility.

Qualitative assessment of ultra-fast non-Grotthuss proton dynamics in S1 excited state of liquid H2O from ab initio time-dependent density functional theory★

NASA Astrophysics Data System (ADS)

Ziaei, Vafa; Bredow, Thomas

2017-11-01

We study qualitatively ultra-fast proton transfer (PT) in the first singlet (S1) state of liquid water (absorption onset) through excited-state dynamics by means of time-dependent density functional theory and ab initio Born-Oppenheimer molecular dynamics. We find that after the initial excitation, a PT occurs in S1 in form of a rapid jump to a neighboring water molecule, on which the proton either may rest for a relatively long period of time (as a consequence of possible defect in the hydrogen bond network) followed by back and forth hops to its neighboring water molecule or from which it further moves to the next water molecule accompanied by back and forth movements. In this way, the proton may become delocalized over a long water wire branch, followed again by back and forth jumps or short localization on a water molecule for some femtoseconds. As a result, the mechanism of PT in S1 is in most cases highly non-Grotthuss-like, delayed and discrete. Furthermore, upon PT an excess charge is ejected to the solvent trap, the so-called solvated electron. The spatial extent of the ejected solvated electron is mainly localized within one solvent shell with overlappings on the nearest neighbor water molecules and delocalizing (diffuse) tails extending beyond the first solvent sphere. During the entire ultra-short excited-state dynamics the remaining OH radical from the initially excited water molecule exhibits an extremely low mobility and is non-reactive. Supplementary material in the form of one pdf file available from the Journal web page at http://https://doi.org/10.1140/epjb/e2017-80329-7.

A microwave-mediated saponification of galactosylceramide and galactosylceramide I3-sulfate and identification of their lyso-compounds by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

PubMed

Taketomi, T; Hara, A; Uemura, K; Kurahashi, H; Sugiyama, E

1996-07-16

Small amounts of galactosylceramide (cerebroside) and galactosylceramide I3-sulfate (sulfatide) obtained from porcine spinal cord and equine kidney were deacylated by a rapid method of microwave-mediated saponification to prepare their lyso-compounds. Mass spectra of their protonated or deprotonated molecular ion peaks were detected by recently developed new technology of a delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometer with reflector detector in positive or negative ion mode. Long chain bases of lysocerebroside and lysosulfatide were different between porcine spinal cord and equine kidney, but similar to each other in the same organ, suggesting their common synthetic pathway. It is noted that the new rapid method can be similarly applied to the deacylation of both cerebroside and sulfatide in contrast to our classical method which was able to be applied to cerebroside, but not to sulfatide.

Probing ultrafast dynamics of solid-density plasma generated by high-contrast intense laser pulses

NASA Astrophysics Data System (ADS)

Jana, Kamalesh; Blackman, David R.; Shaikh, Moniruzzaman; Lad, Amit D.; Sarkar, Deep; Dey, Indranuj; Robinson, Alex P. L.; Pasley, John; Ravindra Kumar, G.

2018-01-01

We present ultrafast dynamics of solid-density plasma created by high-contrast (picosecond contrast ˜10-9), high-intensity (˜4 × 1018 W/cm2) laser pulses using time-resolved pump-probe Doppler spectrometry. Experiments show a rapid rise in blue-shift at early time delay (2-4.3 ps) followed by a rapid fall (4.3-8.3 ps) and then a slow rise in blue-shift at later time delays (>8.3 ps). Simulations show that the early-time observations, specifically the absence of any red-shifting of the reflected probe, can only be reproduced if the front surface is unperturbed by the laser pre-pulse at the moment that the high intensity pulse arrives. A flexible diagnostic which is capable of diagnosing the presence of low-levels of pre-plasma formation would be useful for potential applications in laser-produced proton and ion production, such as cancer therapy and security imaging.

Oxygen delivery and the restoration of the muscle energetic balance following exercise: implications for delayed muscle recovery in patients with COPD.

PubMed

Layec, Gwenael; Hart, Corey R; Trinity, Joel D; Kwon, Oh-Sung; Rossman, Matthew J; Broxterman, Ryan M; Le Fur, Yann; Jeong, Eun-Kee; Richardson, Russell S

2017-07-01

Patients with chronic obstructive pulmonary disease (COPD) experience a delayed recovery from skeletal muscle fatigue following exhaustive exercise that likely contributes to their progressive loss of mobility. As this phenomenon is not well understood, this study sought to examine postexercise peripheral oxygen (O 2 ) transport and muscle metabolism dynamics in patients with COPD, two important determinants of muscle recovery. Twenty-four subjects, 12 nonhypoxemic patients with COPD and 12 healthy subjects with a sedentary lifestyle, performed dynamic plantar flexion exercise at 40% of the maximal work rate (WR max ) with phosphorus magnetic resonance spectroscopy ( 31 P-MRS), near-infrared spectroscopy (NIRS), and vascular Doppler ultrasound assessments. The mean response time of limb blood flow at the offset of exercise was significantly prolonged in patients with COPD (controls: 56 ± 27 s; COPD: 120 ± 87 s; P < 0.05). In contrast, the postexercise time constant for capillary blood flow was not significantly different between groups (controls: 49 ± 23 s; COPD: 51 ± 21 s; P > 0.05). The initial postexercise convective O 2 delivery (controls: 0.15 ± 0.06 l/min; COPD: 0.15 ± 0.06 l/min) and the corresponding oxidative adenosine triphosphate (ATP) demand (controls: 14 ± 6 mM/min; COPD: 14 ± 6 mM/min) in the calf were not significantly different between controls and patients with COPD ( P > 0.05). The phosphocreatine resynthesis time constant (controls: 46 ± 20 s; COPD: 49 ± 21 s), peak mitochondrial phosphorylation rate, and initial proton efflux were also not significantly different between groups ( P > 0.05). Therefore, despite perturbed peripheral hemodynamics, intracellular O 2 availability, proton efflux, and aerobic metabolism recovery in the skeletal muscle of nonhypoxemic patients with COPD are preserved following plantar flexion exercise and thus are unlikely to contribute to the delayed recovery from exercise in this population.

Influence of cell temperature on sulfur dioxide contamination in proton exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Zhai, Y.; Bender, G.; Bethune, K.; Rocheleau, R.

2014-02-01

The effects of temperature on sulfur dioxide (SO2) contamination in PEMFCs are investigated by operating single cells with 2 ppm SO2 in the cathode at different temperatures. Cell performance response shows that voltage degradation was delayed and appears a transition of multiple processes at low temperatures; a similar performance loss is observed when performances reached steady state. The restored performance from the reversible and the irreversible degradations highly depends on temperature. At low temperature, the performance recovery is only negligible with neat air operation (self-recovery), while full recovery is observed after cyclic voltammetry (CV) scanning. As temperature increased, so did the self-recovery performance. However, the total recovery performance decreased. Electrochemical impedance spectroscopy analysis indicates that the potential-dependent poisoning process was delayed at low temperature, and the removal of the sulfur species from Pt/C was inhibited during the self-recovery. Water balance analysis implies that the delay could be attributed to the effect of liquid water scavenging and the mass transport of SO2 in the membrane electrode assemblies. The CV analysis confirms that the decomposition/desorption of the sulfur adsorbates was inhibited and indicates that the SO2 crossover from the cathode to the anode side was also mitigated at low temperature.

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

Remec, Igor; Ronningen, Reginald Martin

The research studied one-step and two-step Isotope Separation on Line (ISOL) targets for future radioactive beam facilities with high driver-beam power through advanced computer simulations. As a target material uranium carbide in the form of foils was used because of increasing demand for actinide targets in rare-isotope beam facilities and because such material was under development in ISAC at TRIUMF when this project started. Simulations of effusion were performed for one-step and two step targets and the effects of target dimensions and foil matrix were studied. Diffusion simulations were limited by availability of diffusion parameters for UC x material atmore » reduced density; however, the viability of the combined diffusion?effusion simulation methodology was demonstrated and could be used to extract physical parameters such as diffusion coefficients and effusion delay times from experimental isotope release curves. Dissipation of the heat from the isotope-producing targets is the limiting factor for high-power beam operation both for the direct and two-step targets. Detailed target models were used to simulate proton beam interactions with the targets to obtain the fission rates and power deposition distributions, which were then applied in the heat transfer calculations to study the performance of the targets. Results indicate that a direct target, with specification matching ISAC TRIUMF target, could operate in 500-MeV proton beam at beam powers up to ~40 kW, producing ~8 10 13 fission/s with maximum temperature in UCx below 2200 C. Targets with larger radius allow higher beam powers and fission rates. For the target radius in the range 9-mm to 30-mm the achievable fission rate increases almost linearly with target radius, however, the effusion delay time also increases linearly with target radius.« less

Studies regarding the mechanism of false negative urea breath tests with proton pump inhibitors.

PubMed

Graham, David Y; Opekun, Antone R; Hammoud, Fadi; Yamaoka, Yoshio; Reddy, Rita; Osato, Michael S; El-Zimaity, Hala M T

2003-05-01

The mechanism of false negative urea breath tests (UBTs) results among proton pump inhibitor (PPI) users is unknown. We studied the time course of PPI-associated negative UBT, the relation to Helicobacter pylori density, and whether gastric acidification would prevent false negative UBT results. In the UBT experiment, H. pylori-infected volunteers received omeprazole 20 mg b.i.d. for 13.5 days. UBTs with citric acid were done before, after 6.5 days of PPI, and 1, 2, 4, 7, and 14 days after therapy. In the culture and histology experiment, after a wash-out of >5 months, nine of the original subjects were rechallenged with omeprazole for 6.5 days. Antral and corpus biopsies for histology and culture were done before and 1 day after PPI administration. Thirty subjects (mean age 42 yr) were enrolled. UBTs were significantly reduced on day 6.5 (p = 0.031); 10 subjects (33%) developed transient negative UBTs. The UBT recovered in all but one subject by the fourth day post-PPI and in all subjects by day 14. In the culture and histology experiment, upon PPI rechallenge, three of nine subjects (33%) had negative UBTs. H. pylori density, whether measured by culture or histology, decreased with PPI therapy; antral biopsies became histologically negative in five subjects and corpus biopsies in three subjects. PPI-induced negative UBT results were related to the anti-H. pylori effect of the PPI. Acidification of the stomach did not prevent false negative UBT results. Three days is likely the minimum delay from stopping PPI until one should perform a test for active infection. A delay of 14 days is preferred.

Altered white matter metabolism in delayed neurologic sequelae after carbon monoxide poisoning: A proton magnetic resonance spectroscopic study.

PubMed

Kuroda, Hiroshi; Fujihara, Kazuo; Mugikura, Shunji; Takahashi, Shoki; Kushimoto, Shigeki; Aoki, Masashi

2016-01-15

Proton magnetic resonance spectroscopy ((1)H-MRS) was recently used to examine altered metabolism in the white matter (WM) of patients experiencing carbon monoxide (CO) poisoning; however, only a small number of patients with delayed neurologic sequelae (DNS) were analyzed. We aimed to detect altered metabolism in the WM of patients with DNS using (1)H-MRS; to explore its clinical relevance in the management of patients experiencing CO poisoning. Patients experiencing acute CO poisoning underwent (1)H-MRS and cerebrospinal fluid (CSF) examination within 1week and at 1month after acute poisoning. Metabolites including choline-containing compounds (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate were measured from the periventricular WM. Myelin basic protein (MBP) concentrations were measured in CSF. Fifty-two patients experiencing acute CO poisoning (15 with DNS, 37 without DNS; median age, 49years; 65% males) underwent (1)H-MRS. Within 1week, NAA/Cr ratios, reflecting neuroaxonal viability, were lower in patients with DNS than in those without DNS (P<0.05). At 1month, when 9 of 15 patients (60%) developed DNS, Cho/Cr ratios were higher, and NAA/Cr and NAA/Cho ratios lower in patients with DNS (P=0.0001, <0.0001, and <0.0001, respectively), indicating increased membrane metabolism and decreased neuroaxonal viability. (1)H-MRS parameter abnormalities correlated with the elevation of MBP in CSF. The presence of a lactate peak was a predictor for a poor long-term outcome. (1)H-MRS within 1week may be useful for predicting DNS development; (1)H-MRS at 1month may be useful for discriminating patients with DNS and predicting long-term outcomes. Copyright © 2015 Elsevier B.V. All rights reserved.

Delayed-type hypersensitivity reactions induced by proton pump inhibitors: A clinical and in vitro T-cell reactivity study.

PubMed

Lin, C-Y; Wang, C-W; Hui, C-Y R; Chang, Y-C; Yang, C-H; Cheng, C-Y; Chen, W-W; Ke, W-M; Chung, W-H

2018-01-01

Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed-type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T-cell reactivity to PPI in PPI-related DHR patients. We retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities. There were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay. PPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Search for nonpointing and delayed photons in the diphoton and missing transverse momentum final state in 8 TeV p p collisions at the LHC using the ATLAS detector

DOE PAGES

Aad, G.; Abbott, B.; Abdallah, J.; ...

2014-12-10

We performed a search, using the full 20.3 fb ₋1 data sample of 8 TeV proton-proton collisions collected in 2012 with the ATLAS detector at the LHC, for photons originating from a displaced vertex due to the decay of a neutral long-lived particle into a photon and an invisible particle. The analysis investigates the diphoton plus missing transverse momentum final state, and is therefore most sensitive to pair production of long-lived particles. The analysis technique exploits the capabilities of the ATLAS electromagnetic calorimeter to make precise measurements of the flight direction, as well as the time of flight, of photons.more » No excess is observed over the Standard Model predictions for background. Lastly, exclusion limits are set within the context of gauge mediated supersymmetry breaking models, with the lightest neutralino being the next-to-lightest supersymmetric particle and decaying into a photon and gravitino with a lifetime in the range from 250 ps to about 100 ns.« less

Gamow-Teller transitions between proton h11/2 and neutron h9/2 partner orbitals in 140I

NASA Astrophysics Data System (ADS)

Moon, B.; Moon, C.-B.; Odahara, A.; Lozeva, R.; Söderström, P.-A.; Nishimura, S.; Yuan, C.; Hong, B.; for theNP1112-RIBF87 Collaboration

2018-04-01

The excited states of the neutron-rich nucleus 140I were, for the first time, investigated by a β-delayed γ-ray spectroscopy. The parent nuclide 140Te was produced through the in-flight fission of the 238U beam at 345 MeV per nucleon on a 9Be target at the Radioactive Isotope Beam Factory (RIBF), RIKEN in Japan. The half-life of 140Te was measured to be 350(5) ms and the spin-parity of ground state of 140I was found to be 2-. The spin-parities of three levels at 926, 1188, and 1787 keV were assigned as 1+ based on log f t values. These allowed Gamow-Teller (G-T) transition-states could be interpreted as the transformation of a neutron in the h9/2 orbital into a proton in the h11/2 orbital. Systematic features of level structures and G-T transitions are discussed in the frameworks of the large-scale shell model and deformed shell model.

Isospin mixing reveals 30P(p, γ) 31S resonance influencing nova nucleosynthesis

DOE PAGES

Bennett, M. B.; Wrede, C.; Brown, B. A.; ...

2016-03-08

Here, the thermonuclear 30P(p, γ) 31S reaction rate is critical for modeling the final elemental and isotopic abundances of ONe nova nucleosynthesis, which affect the calibration of proposed nova thermometers and the identification of presolar nova grains, respectively. Unfortunately, the rate of this reaction is essentially unconstrained experimentally, because the strengths of key 31S proton capture resonance states are not known, largely due to uncertainties in their spins and parities. Using the β decay of 31Cl, we have observed the β-delayed γ decay of a 31S state at E x = 6390.2(7) keV, with a 30P(p, γ) 31S resonance energymore » of E r = 259.3(8) keV, in the middle of the 30P(p, γ) 31S Gamow window for peak nova temperatures. This state exhibits isospin mixing with the nearby isobaric analog state at E x = 6279.0(6) keV, giving it an unambiguous spin and parity of 3/2 + and making it an important l = 0 resonance for proton capture on 30P.« less

DNP enhanced NMR with flip-back recovery

NASA Astrophysics Data System (ADS)

Björgvinsdóttir, Snædís; Walder, Brennan J.; Pinon, Arthur C.; Yarava, Jayasubba Reddy; Emsley, Lyndon

2018-03-01

DNP methods can provide significant sensitivity enhancements in magic angle spinning solid-state NMR, but in systems with long polarization build up times long recycling periods are required to optimize sensitivity. We show how the sensitivity of such experiments can be improved by the classic flip-back method to recover bulk proton magnetization following continuous wave proton heteronuclear decoupling. Experiments were performed on formulations with characteristic build-up times spanning two orders of magnitude: a bulk BDPA radical doped o-terphenyl glass and microcrystalline samples of theophylline, L-histidine monohydrochloride monohydrate, and salicylic acid impregnated by incipient wetness. For these systems, addition of flip-back is simple, improves the sensitivity beyond that provided by modern heteronuclear decoupling methods such as SPINAL-64, and provides optimal sensitivity at shorter recycle delays. We show how to acquire DNP enhanced 2D refocused CP-INADEQUATE spectra with flip-back recovery, and demonstrate that the flip-back recovery method is particularly useful in rapid recycling regimes. We also report Overhauser effect DNP enhancements of over 70 at 592.6 GHz/900 MHz.

[Update of clinical programs using hadrontherapy 2008-2012].

PubMed

Habrand, J-L; Datchary, J; Alapetite, C; Bolle, S; Calugaru, V; Feuvret, L; Helfre, S; Stefan, D; Delacroix, S; Demarzi, L; Dendale, R

2013-10-01

Hadrontherapy, a type of radiation therapy dealing with heavy charged particles, has become for the past decade one of the most sophisticated and attractive approach in the management of cancer. This is related with major technological innovations that have made available, at a relatively cheap cost, compact proton accelerators equipped with rotational gantries. The implementation of pencil beam scanning should also make treatment planning and delivery much easier and faster than conventional approaches. Until now, approximately 100,000 patients have been treated with protons worldwide. Due to more complex technological and biological challenges, light ion therapy - mainly carbon ions - has developed at a lower pace, except in Japan where most of the 15,000 treated patients have been enrolled. Current indications for protons include firstly, locally aggressive tumours non or incompletely resected, that are located close to critical normal structures: ocular melanomas, skull base and spinal canal low grade sarcomas, selected ENT carcinomas (like adenoid cystic); secondly, improvement of tolerance to radiations: delayed, mainly in paediatric malignancies, due to the exquisite sensitivity of organs under development (including to carcinogenesis); immediate, on bone marrow, mucosae… mainly in concomitant radiation-chemotherapy interactions (tested in esophagus, and lung). Most promising indications for carbon ions include inoperable highly radioresistant primaries, such as mucosal melanomas, high grade bone and soft part sarcomas, and pancreatic carcinomas. Altered fractionations are also of interests that could translate in clinical and economical benefits. Controversies have risen whether more common indications, like prostate, should also be explored. Copyright © 2013. Published by Elsevier SAS.

To Flavor or Not to Flavor Extemporaneous Omeprazole Liquid.

PubMed

Chuong, Monica C; Taglieri, Catherine A; Kerr, Stephen G

2017-01-01

Omeprazole is a proton pump inhibitor used to treat the symptoms of gastro esophageal reflux disease, ulcers, excess stomach acid, infection with Helicobacter pylori, and to control the gastric side effects of various drugs. The approved dosage forms in the U.S. are powder in compounding kits, delayed-release granules for oral suspension, oral delayed-release tablets, and oral delayed-release capsules. An extemporaneously compounded unsweetened oral liquid method, published in the International Journal of Pharmaceutical Compounding, was found to be commonly used by pharmacists. This project investigated the robustness of the compendium omeprazole high-performance liquid chromatographic assay in evaluating an oral liquid made from commercial delayed-release pellets, the potency of extemporaneously compounded solutions having a 1.125% v/v flavored versus unflavored samples stored at controlled cold temperatures at different time points, and examining the absorption spectrum of the flavoring agent. As part of the study, stability-indication testing was also conducted. The studies indicate that the chromatographic area under the plasma concentration-time curve of both study groups remained over 90% of the label claim during the follow-up period. The flavor did not significantly impact the pH of the oral liquid. This study further identified (1) an increase in resilient foam formation in the flavored liquid, potentially hindering dosing accuracy, (2) omeprazole is oxidized easily by 3% hydrogen peroxide, and (3) flavoring agent absorbs in an ultraviolet visible spectroscopy spectral range often used in assay detectors for quantification of drug molecules, and could interfere with assay protocols of the same. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

MRS evidence of adequate O2 supply in human skeletal muscle at the onset of exercise

PubMed Central

Richardson, Russell S.; Wary, Claire; Wray, D. Walter; Hoff, Jan; Rossiter, Harry; Layec, Gwenael; Carlier, Pierre G.

2015-01-01

Purpose At exercise onset, intramuscular oxidative energy production responds relatively slowly in comparison to the change in ATP demand. To determine if the slow kinetics of oxidative ATP production is due to inadequate O2 supply or metabolic inertia we studied the kinetics of intramyocellular deoxygenation (deoxy-myoglobin, Mb) and metabolism (phosphocreatine, PCr), using proton (1H) and phosphorus (31P) magnetic resonance spectroscopy (MRS) in 6 healthy subjects (33 ± 5 yrs). Methods Specifically, utilizing dynamic plantar flexion exercise, rest to exercise and recovery was assessed at both 60% of maximum work rate (WRmax) (moderate intensity) and 80% of WRmax (heavy intensity). Results At exercise onset [PCr] fell without delay and with a similar time constant (τ) at both exercise intensities (~33 s). In contrast, the increase in deoxy-Mb was delayed at exercise onset by 5–7 s, after which it increased with kinetics (moderate τ = 37 ± 9 s, and heavy τ = 29 ± 6 s) that were not different from τPCr (p > 0.05). At cessation, deoxy-Mb recovered without a time delay and more rapidly (τ ~20 s) than PCr (τ ~33 s) (p < 0.05). Conclusion using a unique combination of in vivo MRS techniques with high time-resolution, this study revealed a delay in intramuscular de-oxygenation at the onset of exercise, and rapid re-oxygenation kinetics upon cessation. Together these data imply that intramuscular substrate-enzyme interactions, and not O2 availability, determine the exercise onset kinetics of oxidative metabolism in healthy human skeletal muscle. PMID:25830362

Degeneracy breakdown as a source of supernovae Ia

NASA Astrophysics Data System (ADS)

Clavelli, L.

2018-01-01

In a confined system of multiple Fermions, the particles are forced into high energy levels by the Pauli Exclusion Principle. We refer to this system as a Pauli tower. We pursue the investigation of a model for sub-Chandrasekhar supernovae Ia explosions (SNIa) in which the energy stored in the Pauli tower is released to trigger a nuclear deflagration. The simplest physical model for such a degeneracy breakdown and collapse of the Pauli tower is a phase transition to an exactly supersymmetric state in which the scalar partners of protons, neutrons, and leptons become degenerate with the familiar fermions of our world as in the supersymmetric standard model with susy breaking parameters relaxed to zero. We focus on the ability of the susy phase transition model to fit the total SNIa rate as well as the delay time distribution of SNIa after the birth of a progenitor white dwarf. We also study the ejected mass distribution and its correlation with delay time. Finally, we discuss the expected SNIa remnant in the form of a black hole of roughly Jupiter mass and the prospects for detecting such remnants.

Beta decay studies around doubly magic 78Ni

NASA Astrophysics Data System (ADS)

Rykaczewski, Krzysztof

2007-11-01

The main motivations to study very neutron rich nuclei in the ^ 78Ni region are related to the evolution of nuclear structure and to the path of nucleosynthesis within rapid neutron capture. In particular, neutrons filling g9/2 orbital between ^68Ni and ^78Ni affect spin-orbit splitting of proton single-particle states. An increasing beta- delayed neutron emission probabilities are changing the isobaric distributions of nuclei involved in the r-process. The report on the recent results on the decay of most neutron- rich isotopes of copper and gallium [1] will be presented. These proton-induced ^238U fission products were produced and studied at Holifield Radioactive Ion Beam Facility at Oak Ridge using a ``ranging-out'' method [2] for postaccelerated beams purification. In collaboration with Jeff Winger and Sergey Iliushkin, Mississippi State University; Carl Gross and Dan Shapira, ORNL; Carrol Bingham, UTK; Robert Grzywacz, ORNL; Chiara Mazzocchi, Sean Liddick, Steven Padgett, and Mustafa Rajabali, UTK; Jon Batchelder, UNIRIB-ORAU; Edward Zganjar and Andreas Piechaczek, LSU; Christopher Goodin and Joseph Hamilton, Vanderbilt University; and Wojciech Krolas, JIHIR Oak Ridge.[1] J. Winger et al., contr. to INPC, Japan, June 2007[2] C.J. Gross et al., EPJ A 25, s01, 115 (2005)

Animal studies of life shortening and cancer risk from space radiation

NASA Astrophysics Data System (ADS)

Wood, D. H.; Yochmowitz, M. G.; Hardy, K. A.; Salmon, Y. L.

The U. S. Air Force study of the delayed effects of single, total body exposures to simulated space radiation in rhesus monkeys is now in its 21st year. Observations on 301 irradiated and 57 age-matched control animals indicate that life expectancy loss from exposure to protons in the energy range encountered in the Van Allen belts and solar proton events can be expressed as a logarithmic function of the dose. The primary causes of life shortening are cancer and endometriosis (an abnormal proliferation of the lining of the uterus in females). Life shortening estimates permit comparison of the risk associated with space radiation exposures to be compared with that of other occupational and environmental hazards, thereby facilitating risk/benefit decisions in the planning and operational phases of manned space missions. Calculations of the relative risk of fatal cancers in the irradiated subjects reveal that the total body surface dose required to double the risk of death from cancer over a 20-year post exposure period varies with the linear energy transfer (LET) of the radiation. The ability to determine the integrated dose and LET spectrum in space radiation exposures of human is, therefore, critical to the assessment of life-time cancer risk.

Effects of gas-wall partitioning in Teflon tubing and instrumentation on time-resolved measurements of gas-phase organic compounds

NASA Astrophysics Data System (ADS)

Pagonis, Demetrios; Krechmer, Jordan E.; de Gouw, Joost; Jimenez, Jose L.; Ziemann, Paul J.

2017-12-01

Recent studies have demonstrated that organic compounds can partition from the gas phase to the walls in Teflon environmental chambers and that the process can be modeled as absorptive partitioning. Here these studies were extended to investigate gas-wall partitioning of organic compounds in Teflon tubing and inside a proton-transfer-reaction mass spectrometer (PTR-MS) used to monitor compound concentrations. Rapid partitioning of C8-C14 2-ketones and C11-C16 1-alkenes was observed for compounds with saturation concentrations (c∗) in the range of 3 × 104 to 1 × 107 µg m-3, causing delays in instrument response to step-function changes in the concentration of compounds being measured. These delays vary proportionally with tubing length and diameter and inversely with flow rate and c∗. The gas-wall partitioning process that occurs in tubing is similar to what occurs in a gas chromatography column, and the measured delay times (analogous to retention times) were accurately described using a linear chromatography model where the walls were treated as an equivalent absorbing mass that is consistent with values determined for Teflon environmental chambers. The effect of PTR-MS surfaces on delay times was also quantified and incorporated into the model. The model predicts delays of an hour or more for semivolatile compounds measured under commonly employed conditions. These results and the model can enable better quantitative design of sampling systems, in particular when fast response is needed, such as for rapid transients, aircraft, or eddy covariance measurements. They may also allow estimation of c∗ values for unidentified organic compounds detected by mass spectrometry and could be employed to introduce differences in time series of compounds for use with factor analysis methods. Best practices are suggested for sampling organic compounds through Teflon tubing.

Waiting Points in Nova and X-ray burst Nucleosynthesis

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

Sunayama, Tomomi; Oak Ridge Institute for Science Education, Oak Ridge, Tennessee 37831-0117; Smith, Michael S.

2008-05-21

In nova and X-ray burst nucleosynthesis, waiting points are nuclei in the reaction path which delay the nuclear flow towards heavier nuclei, typically because of a weak proton capture reaction and a long {beta}{sup +} lifetime. Waiting points can influence the energy generation and final abundances synthesized in these explosions. We have constructed a systematic, quantitative set of criteria to identify rp-process waiting points, and use them to search for waiting points in post-processing simulations of novae and X-ray bursts. These criteria have been incorporated into the Computational Infrastructure for Nuclear Astrophysics, online at nucastrodata.org, to enable anyone to runmore » customized searches for waiting points.« less

When to Wait for More Evidence? Real Options Analysis in Proton Therapy

PubMed Central

Abrams, Keith R.; de Ruysscher, Dirk; Pijls-Johannesma, Madelon; Peters, Hans J.M.; Beutner, Eric; Lambin, Philippe; Joore, Manuela A.

2011-01-01

Purpose. Trends suggest that cancer spending growth will accelerate. One method for controlling costs is to examine whether the benefits of new technologies are worth the extra costs. However, especially new and emerging technologies are often more costly, while limited clinical evidence of superiority is available. In that situation it is often unclear whether to adopt the new technology now, with the risk of investing in a suboptimal therapy, or to wait for more evidence, with the risk of withholding patients their optimal treatment. This trade-off is especially difficult when it is costly to reverse the decision to adopt a technology, as is the case for proton therapy. Real options analysis, a technique originating from financial economics, assists in making this trade-off. Methods. We examined whether to adopt proton therapy, as compared to stereotactic body radiotherapy, in the treatment of inoperable stage I non-small cell lung cancer. Three options are available: adopt without further research; adopt and undertake a trial; or delay adoption and undertake a trial. The decision depends on the expected net gain of each option, calculated by subtracting its total costs from its expected benefits. Results. In The Netherlands, adopt and trial was found to be the preferred option, with an optimal sample size of 200 patients. Increase of treatment costs abroad and costs of reversal altered the preferred option. Conclusion. We have shown that real options analysis provides a transparent method of weighing the costs and benefits of adopting and/or further researching new and expensive technologies. PMID:22147003

Application of INEPT nitrogen-15 and silicon-29 nuclear magnetic resonance spectrometry to derivatized fulvic acids

USGS Publications Warehouse

Thorn, K.A.; Folan, D.W.; Arterburn, J.B.; Mikita, M.A.; MacCarthy, P.

1989-01-01

Use of the INEPT experiment has been examined in two derivatization studies of the Suwannee River fulvic acid. In the first study, the fulvic acid was derivatized with 15N enriched hydroxylamine. The quantitative 15N NMR spectrum, acquired with a 45° pulse angle, 2.0 second pulse delay and inverse gated decoupling, showed that oximes (390-340 ppm) were the major derivatives, followed by nitriles (270-240 ppm), hydroxamic acids (170-160 ppm), secondary amides (150-115 ppm), and lactams (115-90 ppm). The INEPT 15N NMR spectrum was acquired using refocussing delays and polarization transfer times optimized for signal enhancement of singly protonated nitrogens. INEPT greatly enhanced the amide and lactam resonances, and showed that resonances downfield of 180 ppm in the quantitative spectrum represented nonprotonated nitrogens. In the second study, the fulvic acid was first methylated with diazomethane and then silylated with hexamethyldisilazane. The 29Si NMR spectra exhibited two major peaks, from approximately 33 to 22 ppm, representing silyl esters of carboxylic acids, and from 22 to 13 ppm, representing silyl ethers of alcohols and phenols. The INEPT 29Si NMR spectrum was virtually identical to the quantitative 29Si spectrum, acquired with a 90° pulse angle, 5.0 second pulse delay, inverse gated decoupling, and relaxation reagent. INEPT therefore can be used for quantitative analysis of trimethylsilyl derivatives of the fulvic acid, saving spectrometer time and eliminating the need for relaxation reagents.

Mechanisms of Low Dose Radiation-induced T helper Cell Function

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

Gridley, Daila S.

Exposure to radiation above levels normally encountered on Earth can occur during wartime, accidents such as those at Three Mile Island and Chernobyl, and detonation of “dirty bombs” by terrorists. Relatively high levels of radiation exposure can also occur in certain occupations (low-level waste sites, nuclear power plants, nuclear medicine facilities, airline industry, and space agencies). Depression or dysfunction of the highly radiosensitive cells of the immune system can lead to serious consequences, including increased risk for infections, cancer, hypersensitivity reactions, poor wound healing, and other pathologies. The focus of this research was on the T helper (Th) subset ofmore » lymphocytes that secrete cytokines (proteins), and thus control many actions and interactions of other cell types that make up what is collectively known as the immune system. The Department of Energy (DOE) Low Dose Radiation Program is concerned with mechanisms altered by exposure to high energy photons (x- and gamma-rays), protons and electrons. This study compared, for the first time, the low-dose effects of two of these radiation forms, photons and protons, on the response of Th cells, as well as other cell types with which they communicate. The research provided insights regarding gene expression patterns and capacity to secrete potent immunostimulatory and immunosuppressive cytokines, some of which are implicated in pathophysiological processes. Furthermore, the photon versus proton comparison was important not only to healthy individuals who may be exposed, but also to patients undergoing radiotherapy, since many medical centers in the United States, as well as worldwide, are now building proton accelerators. The overall hypothesis of this study was that whole-body exposure to low-dose photons (gamma-rays) will alter CD4+ Th cell function. We further proposed that exposure to low-dose proton radiation will induce a different pattern of gene and functional changes compared to photons. Over the course of this research, tissues other than spleens were archived and with funding obtained from other sources, including the Department of Radiation Medicine at the Loma Linda University Medical Center, some additional assays were performed. Furthermore, groups of additional mice were included that were pre-exposed to low-dose photons before irradiating with acute photons, protons, and simulated solar particle event (SPE) protons. Hence, the original support together with the additional funding for our research led to generation of much valuable information that was originally not anticipated. Some of the data has already resulted in published articles, manuscripts in review, and a number of presentations at scientific conferences and workshops. Difficulties in reliable and reproducible quantification of secreted cytokines using multi-plex technology delayed completion of this study for a period of time. However, final analyses of the remaining data are currently being performed and should result in additional publications and presentations in the near future. Some of the most notable conclusions, thus far, are briefly summarized below: - Distribution of leukocytes were dependent upon cell type, radiation quality, body compartment analyzed, and time after exposure. Low-dose protons tended to have less effect on numbers of major leukocyte populations and T cell subsets compared to low-dose photons. - The patterns of gene and cytokine expression in CD4+ T cells after protracted low-dose irradiation were significantly modified and highly dependent upon the total dose and time after exposure. - Patterns of gene and cytokine expression differed substantially among groups exposed to low-dose photons versus low-dose protons; differences were also noted among groups exposed to much higher doses of photons, protons, and simulated SPE protons. - Some measurements indicated that exposure to low-dose photon radiation, especially 0.01 Gy, significantly “normalized” at least some adverse effects of simulated SPE protons, thereby suggesting that this low level of radiation may induce protective mechanisms against a relatively large radiation event. - Analysis of signal transduction pathways in CD4+ T cells showed that whole-body priming with 0.01 Gy photons before exposure to simulated SPE protons significantly increased expression of p38MAPK and NF-kappaB, while JNK expression was decreased. Overall, it appears that the p38MAPK signaling pathway may be most important in inducing a radioprotective response.« less

Changes in biogeochemical cycling following forest defoliation by pine wilt disease in Kiryu experimental catchment in Japan

NASA Astrophysics Data System (ADS)

Tokuchi, Naoko; Ohte, Nobuhito; Hobara, Satoru; Kim, Su-Jin; Masanori, Katsuyama

2004-10-01

Changes in nutrient budgets and hydrological processes due to the natural disturbance of pine wilt disease (PWD) were monitored in a small, forested watershed in Japan. The disturbance caused changes in soil nitrogen transformations. Pre-disturbance, mineralized nitrogen remained in the form of NH4+, whereas in disturbed areas most mineralized nitrogen was nitrified. Stream NO3- concentrations increased following PWD. There was a delay between time of disturbance and the increase of NO3- in ground and stream waters. Stream concentrations of NO3- and cations (Ca2+ + Mg2+) were significantly correlated from 1994 to 1996, whereas the correlation among NO3-, H+, and SO42- was significant only in 1995. Although both cation exchange and SO42- adsorption buffered protons, cation exchange was the dominant and continuous mechanism for acid buffering. SO42- adsorption was variable and highly pH dependent. The disturbance also resulted in slight delayed changes of input-output nutrient balances. The nitrogen contribution to PWD litter inputs was 7.39 kmol ha-1, and nitrogen loss from streamwater was less than 0.5 kmol ha-1 year-1 throughout the observation period. This large discrepancy suggested substantial nitrogen immobilization.

Structural design of ketal and acetal blocking groups in two-component chemically amplified positive DUV resists

NASA Astrophysics Data System (ADS)

Mertesdorf, Carlo; Muenzel, Norbert; Holzwarth, Heinz E.; Falcigno, Pasquale A.; Schacht, Hans-Thomas; Rohde, Ottmar; Schulz, Reinhard; Slater, Sydney G.; Frey, David; Nalamasu, Omkaram; Timko, Allen G.; Neenan, Thomas X.

1995-06-01

In the present study, protecting groups of moderate stability, such as acetals and ketals, were investigated as pendant blocking groups in polyvinyl phenols. Polymers were obtained by reacting enol ethers with the phenolic side groups to form acetal or ketal blocked phenols. Decomposition temperatures, glass transition temperatures, and molecular weights of the resulting polymers were monitored and correlated with the protecting group structure. Stability of the protecting groups can be explained by protonation occurring at either of the two oxygen sites, making two cleavage routes possible. Secondary reactions of the released protecting groups in the resist film were investigated and discussed. The structure of the protecting group was designed in order to meet basic resist properties such as resolution/linearity, DOF, post exposure delay latitude and thermal stability. A Canon FPA 4500 (NA equals 0.37) and a GCA XLS exposure tool (NA equals 0.53) were used for the optimization process. A preoptimized resist formulation based on the above criteria exhibits 0.23 micrometers line/space resolution, 0.8 micrometers focus latitude at 0.25 micrometers resolution and approximately two hours post exposure delay latitude.

Metabolic alterations and neurodevelopmental outcome of infants with transposition of the great arteries.

PubMed

Park, I Sook; Yoon, S Young; Min, J Yeon; Kim, Y Hwue; Ko, J Kok; Kim, K Soo; Seo, D Man; Lee, J Hee

2006-01-01

Abnormal neurodevelopment has been reported for infants who were born with transposition of the great arteries (TGA) and underwent arterial switch operation (ASO). This study evaluates the cerebral metabolism of TGA infants at birth and before ASO and neurodevelopment 1 year after ASO. Proton magnetic resonance spectroscopy (1H-MRS) was performed on 16 full-term TGA brains before ASO within 3-6 days after birth. The brain metabolite ratios of [NAA/Cr], [Cho/Cr], and [mI/Cr] evaluated measured. Ten infants were evaluated at 1 year using the Bayley Scales of Infants Development II (BSED II). Cerebral metabolism of infants with TGA was altered in parietal white matter (PWM) and occipital gray matter (OGM) at birth before ASO. One year after ASO, [Cho/Cr] in PWM remained altered, but all metabolic ratios in OGM were normal. The results of BSID II at 1 year showed delayed mental and psychomotor development. This delayed neurodevelopmental outcome may reflect consequences of the altered cerebral metabolism in PWM measured by 1H-MRS. It is speculated that the abnormal hemodynamics due to TGA in utero may be responsible for the impaired cerebral metabolism and the subsequent neurodevelopmental deficit.

The CCONE Code System and its Application to Nuclear Data Evaluation for Fission and Other Reactions

NASA Astrophysics Data System (ADS)

Iwamoto, O.; Iwamoto, N.; Kunieda, S.; Minato, F.; Shibata, K.

2016-01-01

A computer code system, CCONE, was developed for nuclear data evaluation within the JENDL project. The CCONE code system integrates various nuclear reaction models needed to describe nucleon, light charged nuclei up to alpha-particle and photon induced reactions. The code is written in the C++ programming language using an object-oriented technology. At first, it was applied to neutron-induced reaction data on actinides, which were compiled into JENDL Actinide File 2008 and JENDL-4.0. It has been extensively used in various nuclear data evaluations for both actinide and non-actinide nuclei. The CCONE code has been upgraded to nuclear data evaluation at higher incident energies for neutron-, proton-, and photon-induced reactions. It was also used for estimating β-delayed neutron emission. This paper describes the CCONE code system indicating the concept and design of coding and inputs. Details of the formulation for modelings of the direct, pre-equilibrium and compound reactions are presented. Applications to the nuclear data evaluations such as neutron-induced reactions on actinides and medium-heavy nuclei, high-energy nucleon-induced reactions, photonuclear reaction and β-delayed neutron emission are mentioned.

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

Laskin, Julia

In this work, resonant ejection coupled with surface-induced dissociation (SID) in a Fourier transform ion cyclotron resonance mass spectrometer is used to examine fragmentation kinetics of two singly protonated hexapeptides, RYGGFL and KYGGFL, containing the basic arginine residue and less basic lysine residue at the N-terminus. The kinetics of individual reaction channels at different collision energies are probed by applying a short ejection pulse (1 ms) in resonance with the cyclotron frequency of a selected fragment ion and varying the delay time between ion-surface collision and resonant ejection while keeping total reaction delay time constant. Rice-Ramsperger-Kassel-Marcus (RRKM) modeling of themore » experimental data provides accurate threshold energies and activation entropies of individual reaction channels. Substitution of arginine with less basic lysine has a pronounced effect on the observed fragmentation kinetics of several pathways, including the b2 ion formation, but has little or no effect on formation of the b5+H2O fragment ion. The combination of resonant ejection SID, time- and collision energy-resolved SID, and RRKM modeling of both types of experimental data provides a detailed mechanistic understanding of the primary dissociation pathways of complex gaseous ions.« less

Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species.

PubMed

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

2007-06-01

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

Effect of Film Dressing on Acute Radiation Dermatitis Secondary to Proton Beam Therapy

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

Arimura, Takeshi, E-mail: arimura-takeshi@medipolis.org; Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima; Ogino, Takashi

Purpose: Acute radiation dermatitis (ARD) is one of the most common adverse events of proton beam therapy (PBT), and there is currently no effective method to manage ARD. The purpose of this study was to examine the prophylactic effect of a film dressing using Airwall on PBT-induced ARD compared with standard skin managements. Methods and Materials: A total of 271 patients with prostate cancer who were scheduled for PBT at our center were divided into 2 groups based on their own requests: 145 patients (53%) chose Airwall (group A) and 126 patients (47%) received standard treatments (group B). We evaluatedmore » irradiated skin every other day during PBT and followed up once a week for a month after completion of PBT. Results: Grade 0, 1, 2, and 3 dermatitis were seen in 2, 122, 21, and 0 and 0, 65, 57, and 4 patients in groups A and B, respectively (P<.001). Numbers of days to grades 1 and 2 ARD development were 34.9 ± 14.3 and 54.7 ± 10.3 and 31.8 ± 11.3 and 54.4 ± 11.6 in groups A and B, respectively. There were no significant differences between the 2 groups. Eighteen patients (12%) in group A who experienced problems in the region covered with Airwall switched to standard skin care after peeling the film off. Conclusions: Film dressing using Airwall reduced the severity of ARD without delaying the response time of the skin to proton beam irradiation compared with standard skin management. Hence, film dressing is considered a promising measure for preventing ARD secondary to PBT.« less

Coherent evolution of parahydrogen induced polarisation using laser pump, NMR probe spectroscopy: Theoretical framework and experimental observation.

PubMed

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

2017-05-01

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

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

Miyawaki, Daisuke; Murakami, Masao; Demizu, Yusuke

Purpose: To assess the incidence of early delayed or late morbidity of Brain after particle therapy for skull base tumors and head-and-neck cancers. Methods and Materials: Between May 2001 and December 2005, 59 patients with cancerous invasion of the skull base were treated with proton or carbon ion therapy at the Hyogo Ion Beam Medical Center. Adverse events were assessed according to the magnetic resonance imaging findings (late effects of normal tissue-subjective, objective, management, analytic [LENT-SOMA]) and symptoms (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0). Dose-volume histograms were used to analyze the relationship between the dose and volumemore » of the irradiated brain and the occurrence of brain injury. The median follow-up time was 33 months. Results: Of the 48 patients treated with proton therapy and 11 patients treated with carbon ion radiotherapy, 8 (17%) and 7 (64%), respectively, developed radiation-induced brain changes (RIBCs) on magnetic resonance imaging (LENT-SOMA Grade 1-3). Four patients (7%) had some clinical symptoms, such as vertigo and headache (CTCAE Grade 2) or epilepsy (CTCAE Grade 3). The actuarial occurrence rate of RIBCs at 2 and 3 years was 20% and 39%, respectively, with a significant difference in the incidence between the proton and carbon ion radiotherapy groups. The dose-volume histogram analyses revealed significant differences between Brain lobes with and without RIBCs in the actuarial volume of brain lobes receiving high doses. Conclusion: Particle therapies produced minimal symptomatic brain toxicities, but sequential evaluation with magnetic resonance imaging detected a greater incidence of RIBCs. Significant differences were observed in the irradiated brain volume between Brain lobes with and without RIBCs.« less

Pharmacological and Safety Profile of Dexlansoprazole: A New Proton Pump Inhibitor - Implications for Treatment of Gastroesophageal Reflux Disease in the Asia Pacific Region.

PubMed

Goh, Khean Lee; Choi, Myung Gyu; Hsu, Ping I; Chun, Hoon Jai; Mahachai, Varocha; Kachintorn, Udom; Leelakusolvong, Somchai; Kim, Nayoung; Rani, Abdul Aziz; Wong, Benjamin C Y; Wu, Justin; Chiu, Cheng Tang; Shetty, Vikram; Bocobo, Joseph C; Chan, Melchor M; Lin, Jaw-Town

2016-07-30

Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade. Gastroesophageal reflux disease is associated with considerable reductions in subjective well-being and work productivity, as well as increased healthcare use. Proton pump inhibitors (PPIs) are currently the most effective treatment for gastroesophageal reflux disease. However, there are limitations associated with these drugs in terms of partial and non-response. Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication to extend the duration of effective plasma drug concentration. Dexlansoprazole has been shown to be effective for healing of erosive esophagitis, and to improve subjective well-being by controlling 24-hour symptoms. Dexlansoprazole has also been shown to achieve good plasma concentration regardless of administration with food, providing flexible dosing. Studies in healthy volunteers showed no clinically important effects on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition, with no dose adjustment of clopidogrel necessary when coprescribed. This review discusses the role of the new generation PPI, dexlansoprazole, in the treatment of gastroesophageal reflux disease in Asia.

β Decay as a Probe of Explosive Nucleosynthesis in Classical Novae

NASA Astrophysics Data System (ADS)

Wrede, C.; Bennett, M. B.; Liddick, S. N.; Bardayan, D. W.; Bowe, A.; Brown, B. A.; Chen, A. A.; Chipps, K. A.; Cooper, N.; Fry, C.; Glassman, B.; Irvine, D.; José, J.; Langer, C.; Larson, N.; McNeice, E. I.; Meisel, Z.; Montes, F.; Naqvi, F.; Pain, S. D.; O'Malley, P.; Ortez, R.; Ong, W.; Pereira, J.; Pérez-Loureiro, D.; Prokop, C.; Quaglia, J.; Quinn, S.; Santia, M.; Schatz, H.; Schwartz, S. B.; Simon, A.; Shanab, S.; Spyrou, A.; Suchyta, S.; Thiagalingam, E.; Thompson, P.; Walters, M.

Classical novae are common thermonuclear explosions in the Milky Way galaxy, occurring on the surfaces of white-dwarf stars that are accreting hydrogen-rich material from companion stars. Nucleosynthesis in classical novae depends on radiative proton-capture reaction rates on radioactive nuclides. Many of these reactions cannot be measured directly at current accelerator facilities due to the lack of intense, high-quality, radioactive-ion beams at the relevant energies. Since most of these reactions proceed via resonant capture, their rates can be determined indirectly by measuring the properties of the resonances. At the National Superconducting Cyclotron Laboratory, we have used the β-delayed γ decays of 26P and 31Cl to populate resonances in 26Si and 31S and study the radiative proton captures on 25Al and 30P, respectively. These were two out of the three most important nuclear-physics uncertainties associated with the observable products of nova nucleosynthesis. The 26P experiment has enabled a more accurate estimate of the nova contribution to the long-lived Galactic 26Al detected with γ-ray telescopes. The 31Cl experiment, currently under analysis, will calibrate potential nova thermometers and mixing meters based on elemental abundance ratios, and facilitate the identification of pre-solar nova grain candidates found in primitive meteorites based on isotopic ratios.

Pharmacological and Safety Profile of Dexlansoprazole: A New Proton Pump Inhibitor – Implications for Treatment of Gastroesophageal Reflux Disease in the Asia Pacific Region

PubMed Central

Goh, Khean Lee; Choi, Myung Gyu; Hsu, Ping I; Chun, Hoon Jai; Mahachai, Varocha; Kachintorn, Udom; Leelakusolvong, Somchai; Kim, Nayoung; Rani, Abdul Aziz; Wong, Benjamin C Y; Wu, Justin; Chiu, Cheng Tang; Shetty, Vikram; Bocobo, Joseph C; Chan, Melchor M; Lin, Jaw-Town

2016-01-01

Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade. Gastroesophageal reflux disease is associated with considerable reductions in subjective well-being and work productivity, as well as increased healthcare use. Proton pump inhibitors (PPIs) are currently the most effective treatment for gastroesophageal reflux disease. However, there are limitations associated with these drugs in terms of partial and non-response. Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication to extend the duration of effective plasma drug concentration. Dexlansoprazole has been shown to be effective for healing of erosive esophagitis, and to improve subjective well-being by controlling 24-hour symptoms. Dexlansoprazole has also been shown to achieve good plasma concentration regardless of administration with food, providing flexible dosing. Studies in healthy volunteers showed no clinically important effects on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition, with no dose adjustment of clopidogrel necessary when coprescribed. This review discusses the role of the new generation PPI, dexlansoprazole, in the treatment of gastroesophageal reflux disease in Asia. PMID:26932927

Diagnostic methods and recommendations for the cerebral creatine deficiency syndromes.

PubMed

Clark, Joseph F; Cecil, Kim M

2015-03-01

Primary care pediatricians and a variety of specialist physicians strive to define an accurate diagnosis for children presenting with impairment of expressive speech and delay in achieving developmental milestones. Within the past two decades, a group of disorders featuring this presentation have been identified as cerebral creatine deficiency syndromes (CCDS). Patients with these disorders were initially discerned using proton magnetic resonance spectroscopy of the brain within a magnetic resonance imaging (MRI) examination. The objective of this review is to provide the clinician with an overview of the current information available on identifying and treating these conditions. We explain the salient features of creatine metabolism, synthesis, and transport required for normal development. We propose diagnostic approaches for confirming a CCDS diagnosis. Finally, we describe treatment approaches for managing patients with these conditions.

Infantile cobalamin deficiency with cerebral lactate accumulation and sustained choline depletion.

PubMed

Horstmann, M; Neumaier-Probst, E; Lukacs, Z; Steinfeld, R; Ullrich, K; Kohlschütter, A

2003-06-01

A remarkable, intermittent sudden-onset vigilance and movement disorder in an exclusively breast-fed infant is reported, which was caused by cobalamin depletion due to maternal vitamin B12 malabsorption. The lack of cobalamin caused a severe encephalopathy in the infant, whose brain displayed a striking loss of volume and a delay of myelination. Proton magnetic resonance spectroscopy revealed an accumulation of lactate in the gray and white matter of the brain and a sustained depletion of choline-containing compounds in the white matter, reflecting a reversible disturbance of oxidative energy metabolism in brain cells and a long-lasting hypomyelination disorder. The clinical picture in conjunction with MRI and spectroscopic data of this case study yields more insight into the functions of cobalamin in the cerebral metabolism.

Macroalgal spore dysfunction: ocean acidification delays and weakens adhesion.

PubMed

Guenther, Rebecca; Miklasz, Kevin; Carrington, Emily; Martone, Patrick T

2018-04-01

Early life stages of marine organisms are predicted to be vulnerable to ocean acidification. For macroalgae, reproduction and population persistence rely on spores to settle, adhere and continue the algal life cycle, yet the effect of ocean acidification on this critical life stage has been largely overlooked. We explicitly tested the biomechanical impact of reduced pH on early spore adhesion. We developed a shear flume to examine the effect of reduced pH on spore attachment time and strength in two intertidal rhodophyte macroalgae, one calcified (Corallina vancouveriensis) and one noncalcified (Polyostea robusta). Reduced pH delayed spore attachment of both species by 40%-52% and weakened attachment strength in C. vancouveriensis, causing spores to dislodge at lower flow-induced shear forces, but had no effect on the attachment strength of P. robusta. Results are consistent with our prediction that reduced pH disrupts proper curing and gel formation of spore adhesives (anionic polysaccharides and glycoproteins) via protonation and cation displacement, although experimental verification is needed. Our results demonstrate that ocean acidification negatively, and differentially, impacts spore adhesion in two macroalgae. If results hold in field conditions, reduced ocean pH has the potential to impact macroalgal communities via spore dysfunction, regardless of the physiological tolerance of mature thalli. © 2017 Phycological Society of America.

High field hyperpolarization-EXSY experiment for fast determination of dissociation rates in SABRE complexes

NASA Astrophysics Data System (ADS)

Hermkens, Niels K. J.; Feiters, Martin C.; Rutjes, Floris P. J. T.; Wijmenga, Sybren S.; Tessari, Marco

2017-03-01

SABRE (Signal Amplification By Reversible Exchange) is a nuclear spin hyperpolarization technique based on the reversible concurrent binding of small molecules and para-hydrogen (p-H2) to an iridium metal complex in solution. At low magnetic field, spontaneous conversion of p-H2 spin order to enhanced longitudinal magnetization of the nuclear spins of the other ligands occurs. Subsequent complex dissociation results in hyperpolarized substrate molecules in solution. The lifetime of this complex plays a crucial role in attained SABRE NMR signal enhancements. Depending on the ligands, vastly different dissociation rates have been previously measured using EXSY or selective inversion experiments. However, both these approaches are generally time-consuming due to the long recycle delays (up to 2 min) necessary to reach thermal equilibrium for the nuclear spins of interest. In the cases of dilute solutions, signal averaging aggravates the problem, further extending the experimental time. Here, a new approach is proposed based on coherent hyperpolarization transfer to substrate protons in asymmetric complexes at high magnetic field. We have previously shown that such asymmetric complexes are important for application of SABRE to dilute substrates. Our results demonstrate that a series of high sensitivity EXSY spectra can be collected in a short experimental time thanks to the NMR signal enhancement and much shorter recycle delay.

A Multicenter, Randomized, Open-Label, Pharmacokinetics and Safety Study of Pantoprazole Tablets in Children and Adolescents Aged 6 Through 16 Years With GERD

PubMed Central

Ward, Robert M.; Kearns, Gregory L.; Tammara, Brinda; Bishop, Phyllis; O’Gorman, Molly A.; James, Laura P.; Katz, Mitchell H.; Maguire, Mary K.; Rath, Natalie; Meng, Xu; Comer, Gail M.

2011-01-01

SUMMARY Children with GERD may benefit from gastric acid suppression with proton pump inhibitors such as pantoprazole. Effective treatment with pantoprazole requires correct dosing and understanding of the drug’s kinetic profile in children. The aim of these studies was to characterize the pharmacokinetic (PK) profile of single and multiple doses of pantoprazole delayed-release tablets in pediatric patients with GERD aged ≥6 through 11 years (study 1) and 12 through 16 years (study 2). Patients were randomly assigned to receive pantoprazole 20 or 40 mg once daily. Plasma pantoprazole concentrations were obtained at intervals through 12 hours after the single dose, and at 2 and 4 hours after multiple doses for PK evaluation. PK parameters were derived by standard noncompartmental methods and examined as a function of both drug dose and patient age. Safety was also monitored. Pantoprazole PK was dose independent (when dose normalized) and similar toPK reported from adult studies. There was no evidence of accumulation with multiple dosing or reports of serious drug-associated adverse events. In children aged 6 to 16 years with GERD, currently available pantoprazole delayed-release tablets can be used to provide systemic exposure similar to that in adults. PMID:20852004

Decay studies of neutron deficient nuclei near the Z =64 subshell: sup 142 Dy, sup 140,142 Tb, sup 140,142 Gd, sup 140,142 Eu, sup 142 Sm, and

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

Firestone, R.B.; Gilat, J.; Nitschke, J.M.

The electron-capture and {beta}{sup +}-decay branchings (EC/{beta}{sup +}) and delayed proton decays of {ital A}=142 isotopes with 61{le}{ital Z}{le}66 and {ital A}=140 isotopes with 63{le}{ital Z}{le}65 were investigated with the OASIS facility on-line at the Lawrence Berkeley Laboratory SuperHILAC. Electron capture and positron-decay emission probabilities have been determined for {sup 142}Pm and {sup 142}Sm decays, and extensive decay schemes have been constructed for {sup 142}Eu{sup {ital g}}(2.34{plus minus}0.12 s), {sup 142}Gd(70.2{plus minus}0.6 s), {sup 140}Eu(1.51{plus minus}0.02 s), and {sup 140}Gd(15.8{plus minus}0.4 s). Decay schemes for the new isotopes {sup 142}Tb{sup {ital g}}(597{plus minus}17 ms), {sup 142}Tb{sup {ital m}}(303{plus minus}17 ms),more » {sup 142}Dy(2.3{plus minus}0.3 s), {sup 140}Eu{sup {ital m}}(125{plus minus}2 ms), and {sup 140}Tb(2.4{plus minus}0.2 s) are also presented. We have assigned {gamma} rays to these isotopes on the basis of {gamma}{gamma} and {ital x}{gamma} coincidences, and from half-life determinations. Electron-capture and {beta}{sup +}-decay branchings were measured for each decay, and {beta}-delayed proton branchings were determined for {sup 142}Dy, {sup 142}Tb, and {sup 140}Tb decays. {ital Q}{sub EC} values, derived from the measured EC/{beta}{sup +} branchings and the level schemes are compared with those from the Wapstra and Audi mass evaluation and the Liran and Zeldes mass calculation. The systematics of the {ital N}=77 isomer decays are discussed, and the intense 0{sup +}{r arrow}1{sup +} and 1{sup +}{r arrow}0{sup +} ground-state beta decays are compared with shell-model predictions for simple spin-flip transitions.« less

Nuclear structure and weak rates of heavy waiting point nuclei under rp-process conditions

NASA Astrophysics Data System (ADS)

Nabi, Jameel-Un; Böyükata, Mahmut

2017-01-01

The structure and the weak interaction mediated rates of the heavy waiting point (WP) nuclei 80Zr, 84Mo, 88Ru, 92Pd and 96Cd along N = Z line were studied within the interacting boson model-1 (IBM-1) and the proton-neutron quasi-particle random phase approximation (pn-QRPA). The energy levels of the N = Z WP nuclei were calculated by fitting the essential parameters of IBM-1 Hamiltonian and their geometric shapes were predicted by plotting potential energy surfaces (PESs). Half-lives, continuum electron capture rates, positron decay rates, electron capture cross sections of WP nuclei, energy rates of β-delayed protons and their emission probabilities were later calculated using the pn-QRPA. The calculated Gamow-Teller strength distributions were compared with previous calculation. We present positron decay and continuum electron capture rates on these WP nuclei under rp-process conditions using the same model. For the rp-process conditions, the calculated total weak rates are twice the Skyrme HF+BCS+QRPA rates for 80Zr. For remaining nuclei the two calculations compare well. The electron capture rates are significant and compete well with the corresponding positron decay rates under rp-process conditions. The finding of the present study supports that electron capture rates form an integral part of the weak rates under rp-process conditions and has an important role for the nuclear model calculations.

TIME STRUCTURE OF GAMMA-RAY SIGNALS GENERATED IN LINE-OF-SIGHT INTERACTIONS OF COSMIC RAYS FROM DISTANT BLAZARS

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

Prosekin, Anton; Aharonian, Felix; Essey, Warren

2012-10-01

Blazars are expected to produce both gamma rays and cosmic rays. Therefore, observed high-energy gamma rays from distant blazars may contain a significant contribution from secondary gamma rays produced along the line of sight by the interactions of cosmic-ray protons with background photons. Unlike the standard models of blazars that consider only the primary photons emitted at the source, models that include the cosmic-ray contribution predict that even {approx}10 TeV photons should be detectable from distant objects with redshifts as high as z {>=} 0.1. Secondary photons contribute to signals of point sources only if the intergalactic magnetic fields aremore » very small, B {approx}< 10{sup -14} G, and their detection can be used to set upper bounds on magnetic fields along the line of sight. Secondary gamma rays have distinct spectral and temporal features. We explore the temporal properties of such signals using a semi-analytical formalism and detailed numerical simulations, which account for all the relevant processes, including magnetic deflections. In particular, we elucidate the interplay of time delays coming from the proton deflections and from the electromagnetic cascade, and we find that, at multi-TeV energies, secondary gamma rays can show variability on timescales of years for B {approx} 10{sup -15} G.« less

[Gastrointestinal bleeding].

PubMed

Lanas, Ángel

2015-09-01

In the Digestive Disease Week in 2015 there have been some new contributions in the field of gastrointestinal bleeding that deserve to be highlighted. Treatment of celecoxib with a proton pump inhibitor is safer than treatment with nonselective NSAID and a proton pump inhibitor in high risk gastrointestinal and cardiovascular patients who mostly also take acetylsalicylic acid. Several studies confirm the need to restart the antiplatelet or anticoagulant therapy at an early stage after a gastrointestinal hemorrhage. The need for urgent endoscopy before 6-12 h after the onset of upper gastrointestinal bleeding episode may be beneficial in patients with hemodynamic instability and high risk for comorbidity. It is confirmed that in Western but not in Japanese populations, gastrointestinal bleeding episodes admitted to hospital during weekend days are associated with a worse prognosis associated with delays in the clinical management of the events. The strategy of a restrictive policy on blood transfusions during an upper GI bleeding event has been challenged. Several studies have shown the benefit of identifying the bleeding vessel in non varicose underlying gastric lesions by Doppler ultrasound which allows direct endoscopic therapy in the patient with upper GI bleeding. Finally, it has been reported that lower gastrointestinal bleeding diverticula band ligation or hemoclipping are both safe and have the same long-term outcomes. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Decreased Taurine and Creatine in the Thalamus May Relate to Behavioral Impairments in Ethanol-Fed Mice: A Pilot Study of Proton Magnetic Resonance Spectroscopy.

PubMed

Xu, Su; Zhu, Wenjun; Wan, Yamin; Wang, JiaBei; Chen, Xi; Pi, Liya; Lobo, Mary Kay; Ren, Bin; Ying, Zhekang; Morris, Michael; Cao, Qi

2018-01-01

Minimal hepatic encephalopathy (MHE) is highly prevalent, observed in up to 80% of patients with liver dysfunction. Minimal hepatic encephalopathy is defined as hepatic encephalopathy with cognitive deficits and no grossly evident neurologic abnormalities. Clinical management may be delayed due to the lack of in vivo quantitative methods needed to reveal changes in brain neurobiochemical biomarkers. To gain insight into the development of alcoholic liver disease-induced neurological dysfunction (NDF), a mouse model of late-stage alcoholic liver fibrosis (LALF) was used to investigate changes in neurochemical levels in the thalamus and hippocampus that relate to behavioral changes. Proton magnetic resonance spectroscopy of the brain and behavioral testing were performed to determine neurochemical alterations and their relationships to behavioral changes in LALF. Glutamine levels were higher in both the thalamus and hippocampus of alcohol-treated mice than in controls. Thalamic levels of taurine and creatine were significantly diminished and strongly correlated with alcohol-induced behavioral changes. Chronic long-term alcohol consumption gives rise to advanced liver fibrosis, neurochemical changes in the nuclei, and behavioral changes which may be linked to NDF. Magnetic resonance spectroscopy represents a sensitive and noninvasive measurement of pathological alterations in the brain, which may provide insight into the pathogenesis underlying the development of MHE.

Uncorrelated Far Active Galactic Nuclei Flaring with Their Delayed Ultra High Energy Cosmic Rays Events

NASA Astrophysics Data System (ADS)

Fargion, Daniele; Oliva, Pietro; De Sanctis Lucentini, Pier Giorgio

The most distant Active Galactic Nuclei (AGN), within the allowed Greisen-Zatsepin-Kuzmin (GZK) cut-off radius ( ≲ 100 Mpc), have been recently candidate by many authors as the best location for the observed Ultra High Energy Cosmic Rays (UHECR) origination. Indeed, the apparent homogeneity and isotropy of recent UHECR signals seems to require a far cosmic isotropic and homogeneous scenario, involving a proton UHECR courier: our galaxy or nearest local group or super galactic plane (ruled by the Virgo cluster) are too near and apparently too anisotropic to be in agreement with the (Pierre Auger Observatory (PAO) and Telescope Array (TA) almost-homogeneous data sample. However, the few and mild UHECR observed clustering, the so called North and South Hot Spots, are smeared in wide (±18°) solid angles. Their consequent random walk flight from most far GZK UHECR sources, nearly at 100 Mpc, must be delayed — withrespect to a straight AGN photon gamma flaring arrival trajectory — at least by a million years. During this time, the AGN jet blazing signal, its probable axis deflection (such as the helical jet in Mrk 501), its miss alignment or even its almost certain exhaust activity, may lead to a complete misleading correlation between present UHECR events and a much earlier active AGN ejection. UHECR maps may be anyway related to galactic or nearest (Cen A, M82) AGN extragalactic UHECR sources shining in twin Hot Spot. Therefore we defend our (quite different) scenario where UHECR are mostly made by lightest UHECR nuclei originated by nearby AGN sources, or few galactic sources, whose delayed signals are reaching us within few thousand years in the observed smeared sky areas.

SU-E-J-78: Adaptive Planning Workflow in a Pencil Beam Scanning Proton Therapy Center

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

Blakey, M; Price, S; Robison, B

Purpose: The susceptibility of proton therapy to changes in patient setup and anatomy necessitates an adaptive planning process. With the right planning tools and clinical workflow, an adaptive plan can be created in a timely manner without adding significant workload to the treatment planning staff. Methods: In our center, a weekly QA CT is performed on most patients to assess setup, anatomy change, and tumor response. The QA CT is fused to the treatment planning CT, the contours are transferred via deformable registration, and the plan dose is recalculated on the QA CT. A physicist assesses the dose distribution, andmore » an adaptive plan is requested based on tumor coverage or OAR dose changes. After the physician confirms or alters the deformed contours, a dosimetrist develops an adaptive plan using our TPS adaptation module. The plan is assessed for robustness and is then reviewed by the physician. Patient QA is performed within three days following the first adapted treatment. Results: Of the patients who received QA CTs, 19% required at least one adaptive plan (18.5% H&N, 18.5% brain, 11.1% breast, 14.8% chestwall, 14.8% lung, 18.5% pelvis and 3.8% abdomen). Of these patients, 14% went on a break, while the remainder was treated with the previous plan during the re-planning process. Adaptive plans were performed based on tumor shrinkage, anatomy change or positioning uncertainties for 37.9%, 44.8%, and 17.3% of the patients, respectively. On average, 3 full days are required between the QA CT and the first adapted plan treatment. Conclusion: Adaptive planning is a crucial component of proton therapy and should be applied to any site when the QA CT shows significant deviation from the plan. With an efficient workflow, an adaptive plan can be applied without delaying patient treatment or burdening the dosimetry and medical physics team.« less

PET/CT imaging for treatment verification after proton therapy: A study with plastic phantoms and metallic implants

PubMed Central

Parodi, Katia; Paganetti, Harald; Cascio, Ethan; Flanz, Jacob B.; Bonab, Ali A.; Alpert, Nathaniel M.; Lohmann, Kevin; Bortfeld, Thomas

2008-01-01

The feasibility of off-line positron emission tomography/computed tomography (PET/CT) for routine three dimensional in-vivo treatment verification of proton radiation therapy is currently under investigation at Massachusetts General Hospital in Boston. In preparation for clinical trials, phantom experiments were carried out to investigate the sensitivity and accuracy of the method depending on irradiation and imaging parameters. Furthermore, they addressed the feasibility of PET/CT as a robust verification tool in the presence of metallic implants. These produce x-ray CT artifacts and fluence perturbations which may compromise the accuracy of treatment planning algorithms. Spread-out Bragg peak proton fields were delivered to different phantoms consisting of polymethylmethacrylate (PMMA), PMMA stacked with lung and bone equivalent materials, and PMMA with titanium rods to mimic implants in patients. PET data were acquired in list mode starting within 20 min after irradiation at a commercial luthetium-oxyorthosilicate (LSO)-based PET/CT scanner. The amount and spatial distribution of the measured activity could be well reproduced by calculations based on the GEANT4 and FLUKA Monte Carlo codes. This phantom study supports the potential of millimeter accuracy for range monitoring and lateral field position verification even after low therapeutic dose exposures of 2 Gy, despite the delay between irradiation and imaging. It also indicates the value of PET for treatment verification in the presence of metallic implants, demonstrating a higher sensitivity to fluence perturbations in comparison to a commercial analytical treatment planning system. Finally, it addresses the suitability of LSO-based PET detectors for hadron therapy monitoring. This unconventional application of PET involves countrates which are orders of magnitude lower than in diagnostic tracer imaging, i.e., the signal of interest is comparable to the noise originating from the intrinsic radioactivity of the detector itself. In addition to PET alone, PET/CT imaging provides accurate information on the position of the imaged object and may assess possible anatomical changes during fractionated radiotherapy in clinical applications. PMID:17388158

High field hyperpolarization-EXSY experiment for fast determination of dissociation rates in SABRE complexes.

PubMed

Hermkens, Niels K J; Feiters, Martin C; Rutjes, Floris P J T; Wijmenga, Sybren S; Tessari, Marco

2017-03-01

SABRE (Signal Amplification By Reversible Exchange) is a nuclear spin hyperpolarization technique based on the reversible concurrent binding of small molecules and para-hydrogen (p-H 2 ) to an iridium metal complex in solution. At low magnetic field, spontaneous conversion of p-H 2 spin order to enhanced longitudinal magnetization of the nuclear spins of the other ligands occurs. Subsequent complex dissociation results in hyperpolarized substrate molecules in solution. The lifetime of this complex plays a crucial role in attained SABRE NMR signal enhancements. Depending on the ligands, vastly different dissociation rates have been previously measured using EXSY or selective inversion experiments. However, both these approaches are generally time-consuming due to the long recycle delays (up to 2min) necessary to reach thermal equilibrium for the nuclear spins of interest. In the cases of dilute solutions, signal averaging aggravates the problem, further extending the experimental time. Here, a new approach is proposed based on coherent hyperpolarization transfer to substrate protons in asymmetric complexes at high magnetic field. We have previously shown that such asymmetric complexes are important for application of SABRE to dilute substrates. Our results demonstrate that a series of high sensitivity EXSY spectra can be collected in a short experimental time thanks to the NMR signal enhancement and much shorter recycle delay. Copyright © 2017 Elsevier Inc. All rights reserved.

Angular-split/temporal-delay approach to ultrafast protein dynamics at XFELs.

PubMed

Ren, Zhong; Yang, Xiaojing

2016-07-01

X-ray crystallography promises direct insights into electron-density changes that lead to and arise from structural changes such as electron and proton transfer and the formation, rupture and isomerization of chemical bonds. The ultrashort pulses of hard X-rays produced by free-electron lasers present an exciting opportunity for capturing ultrafast structural events in biological macromolecules within femtoseconds after photoexcitation. However, shot-to-shot fluctuations, which are inherent to the very process of self-amplified spontaneous emission (SASE) that generates the ultrashort X-ray pulses, are a major source of noise that may conceal signals from structural changes. Here, a new approach is proposed to angularly split a single SASE pulse and to produce a temporal delay of picoseconds between the split pulses. These split pulses will allow the probing of two distinct states before and after photoexcitation triggered by a laser pulse between the split X-ray pulses. The split pulses originate from a single SASE pulse and share many common properties; thus, noise arising from shot-to-shot fluctuations is self-canceling. The unambiguous interpretation of ultrafast structural changes would require diffraction data at atomic resolution, as these changes may or may not involve any atomic displacement. This approach, in combination with the strategy of serial crystallography, offers a solution to study ultrafast dynamics of light-initiated biochemical reactions or biological processes at atomic resolution.

Design study of an in situ PET scanner for use in proton beam therapy

NASA Astrophysics Data System (ADS)

Surti, S.; Zou, W.; Daube-Witherspoon, M. E.; McDonough, J.; Karp, J. S.

2011-05-01

Proton beam therapy can deliver a high radiation dose to a tumor without significant damage to surrounding healthy tissue or organs. One way of verifying the delivered dose distribution is to image the short-lived positron emitters produced by the proton beam as it travels through the patient. A potential solution to the limitations of PET imaging in proton beam therapy is the development of a high sensitivity, in situ PET scanner that starts PET imaging almost immediately after patient irradiation while the patient is still lying on the treatment bed. A partial ring PET design is needed for this application in order to avoid interference between the PET detectors and the proton beam, as well as restrictions on patient positioning on the couch. A partial ring also allows us to optimize the detector separation (and hence the sensitivity) for different patient sizes. Our goal in this investigation is to evaluate an in situ PET scanner design for use in proton therapy that provides tomographic imaging in a partial ring scanner design using time-of-flight (TOF) information and an iterative reconstruction algorithm. GEANT4 simulation of an incident proton beam was used to produce a positron emitter distribution, which was parameterized and then used as the source distribution inside a water-filled cylinder for EGS4 simulations of a PET system. Design optimization studies were performed as a function of crystal type and size, system timing resolution, scanner angular coverage and number of positron emitter decays. Data analysis was performed to measure the accuracy of the reconstructed positron emitter distribution as well as the range of the positron emitter distribution. We simulated scanners with varying crystal sizes (2-4 mm) and type (LYSO and LaBr3) and our results indicate that 4 mm wide LYSO or LaBr3 crystals (resulting in 4-5 mm spatial resolution) are adequate; for a full-ring, non-TOF scanner we predict a low bias (<0.6 mm) and a good precision (<1 mm) in the estimated range relative to the simulated positron distribution. We then varied the angular acceptance of the scanner ranging from 1/2 to 2/3 of 2π a partial ring TOF imaging with good timing resolution (<=600 ps) is necessary to produce accurate tomographic images. A two-third ring scanner with 300 ps timing resolution leads to a bias of 1.0 mm and a precision of 1.4 mm in the range estimate. With a timing resolution of 600 ps, the bias increases to 2.0 mm while the precision in the range estimate is similar. For a half-ring scanner design, more distortions are present in the image, which is characterized by the increased error in the profile difference estimate. We varied the number of positron decays imaged by the PET scanner by an order of magnitude and we observe some decrease in the precision of the range estimate for lower number of decays, but all partial ring scanner designs studied have a precision <=1.5 mm. The largest number tested, 150 M total positron decays, is considered realistic for a clinical fraction of delivered dose, while the range of positron decays investigated in this work covers a variable number of situations corresponding to delays in scan start time and the total scan time. Thus, we conclude that for partial ring systems, an angular acceptance of at least 1/2 (of 2π) together with timing resolution of 300 ps is needed to achieve accurate and precise range estimates. With 600 ps timing resolution an angular acceptance of 2/3 (of 2π) is required to achieve satisfactory range estimates. These results indicate that it would be feasible to develop a partial-ring dedicated PET scanner based on either LaBr3 or LYSO to accurately characterize the proton dose for therapy planning.

Hybrid quadrupole mass filter/quadrupole ion trap/time-of-flight-mass spectrometer for infrared multiple photon dissociation spectroscopy of mass-selected ions

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

Gulyuz, Kerim; Stedwell, Corey N.; Wang Da

2011-05-15

We present a laboratory-constructed mass spectrometer optimized for recording infrared multiple photon dissociation (IRMPD) spectra of mass-selected ions using a benchtop tunable infrared optical parametric oscillator/amplifier (OPO/A). The instrument is equipped with two ionization sources, an electrospray ionization source, as well as an electron ionization source for troubleshooting. This hybrid mass spectrometer is composed of a quadrupole mass filter for mass selection, a reduced pressure ({approx}10{sup -5} Torr) quadrupole ion trap (QIT) for OPO irradiation, and a reflectron time-of-flight drift tube for detecting the remaining precursor and photofragment ions. A helium gas pulse is introduced into the QIT to temporarilymore » increase the pressure and hence enhance the trapping efficiency of axially injected ions. After a brief pump-down delay, the compact ion cloud is subjected to the focused output from the continuous wave OPO. In a recent study, we implemented this setup in the study of protonated tryptophan, TrpH{sup +}, as well as collision-induced dissociation products of this protonated amino acid [W. K. Mino, Jr., K. Gulyuz, D. Wang, C. N. Stedwell, and N. C. Polfer, J. Phys. Chem. Lett. 2, 299 (2011)]. Here, we give a more detailed account on the figures of merit of such IRMPD experiments. The appreciable photodissociation yields in these measurements demonstrate that IRMPD spectroscopy of covalently bound ions can be routinely carried out using benchtop OPO setups.« less

THE CENTAURUS A ULTRAHIGH-ENERGY COSMIC-RAY EXCESS AND THE LOCAL EXTRAGALACTIC MAGNETIC FIELD

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

Yueksel, Hasan; Kronberg, Philipp P.; Stanev, Todor

2012-10-10

The ultrahigh-energy cosmic-ray (UHECR) anisotropies discovered by the Pierre Auger Observatory provide the potential to finally address both the particle origins and properties of the nearby extragalactic magnetic field (EGMF). We examine the implications of the excess of {approx}10{sup 20} eV events around the nearby radio galaxy Centaurus A. We find that, if Cen A is the source of these cosmic rays, the angular distribution of events constrains the EGMF strength within several Mpc of the Milky Way to {approx}> 20 nG for an assumed primary proton composition. Our conclusions suggest that either the observed excess is a statistical anomalymore » or the local EGMF is stronger than conventionally thought. We discuss several implications, including UHECR scattering from more distant sources, time delays from transient sources, and the possibility of using magnetic lensing signatures to attain tighter constraints.« less

[Non-Helicobacter pylori, Non-nonsteroidal Anti-inflammatory Drug Peptic Ulcer Disease].

PubMed

Chang, Young Woon

2016-06-25

Non-Helicobacter pylori, non-NSAID peptic ulcer disease (PUD), termed idiopathic PUD, is increasing in Korea. Diagnosis is based on exclusion of common causes such as H. pylori infection, infection with other pathogens, surreptitious ulcerogenic drugs, malignancy, and uncommon systemic diseases with upper gastrointestinal manifestations. The clinical course of idiopathic PUD is delayed ulcer healing, higher recurrence, higher re-bleeding after initial ulcer healing, and higher mortality than the other types of PUD. Genetic predisposition, older age, chronic mesenteric ischemia, cigarette smoking, concomitant systemic diseases, and psychological stress are considered risk factors for idiopathic PUD. Diagnosis of idiopathic PUD should systematically explore all possible causes. Management of this disease is to treat underlying disease followed by regular endoscopic surveillance to confirm ulcer healing. Continuous proton pump inhibitor therapy is an option for patients who respond poorly to the standard ulcer regimen.

Searching for topological defect dark matter via nongravitational signatures.

PubMed

Stadnik, Y V; Flambaum, V V

2014-10-10

We propose schemes for the detection of topological defect dark matter using pulsars and other luminous extraterrestrial systems via nongravitational signatures. The dark matter field, which makes up a defect, may interact with standard model particles, including quarks and the photon, resulting in the alteration of their masses. When a topological defect passes through a pulsar, its mass, radius, and internal structure may be altered, resulting in a pulsar "quake." A topological defect may also function as a cosmic dielectric material with a distinctive frequency-dependent index of refraction, which would give rise to the time delay of a periodic extraterrestrial light or radio signal, and the dispersion of a light or radio source in a manner distinct to a gravitational lens. A topological defect passing through Earth may alter Earth's period of rotation and give rise to temporary nonzero electric dipole moments for an electron, proton, neutron, nuclei and atoms.

WE-D-BRB-00: Basics of Proton Therapy

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

NONE

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

Protons and how they are transported by proton pumps.

PubMed

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

2009-01-01

The very high mobility of protons in aqueous solutions demands special features of membrane proton transporters to sustain efficient yet regulated proton transport across biological membranes. By the use of the chemical energy of ATP, plasma-membrane-embedded ATPases extrude protons from cells of plants and fungi to generate electrochemical proton gradients. The recently published crystal structure of a plasma membrane H(+)-ATPase contributes to our knowledge about the mechanism of these essential enzymes. Taking the biochemical and structural data together, we are now able to describe the basic molecular components that allow the plasma membrane proton H(+)-ATPase to carry out proton transport against large membrane potentials. When divergent proton pumps such as the plasma membrane H(+)-ATPase, bacteriorhodopsin, and F(O)F(1) ATP synthase are compared, unifying mechanistic premises for biological proton pumps emerge. Most notably, the minimal pumping apparatus of all pumps consists of a central proton acceptor/donor, a positively charged residue to control pK(a) changes of the proton acceptor/donor, and bound water molecules to facilitate rapid proton transport along proton wires.

Three new defined proton affinities for polybasic molecules in the gas-phase: Proton microaffinity, proton macroaffinity and proton overallaffinity

NASA Astrophysics Data System (ADS)

Salehzadeh, Sadegh; Bayat, Mehdi

2006-08-01

A theoretical study on complete protonation of a series of tetrabasic molecules with general formula N[(CH 2) nNH 2][(CH 2) mNH 2][(CH 2) pNH 2] (tren, pee, ppe, tpt, epb and ppb) is reported. For first time, three kinds of gas-phase proton affinities for each polybasic molecule are defined as: 'proton microaffinity (PA n, i)', 'proton macroaffinity (PA)' and 'proton overall affinity ( PA)'. The variations of calculated logPA in the series of these molecules is very similar to that of their measured log Kn. There is also a good correlation between the calculated gas-phase proton macroaffinities and proton overallaffinities with corresponding equilibrium macroconstants and overall protonation constants in solution.

WE-D-BRB-02: Proton Treatment Planning and Beam Optimization

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

Pankuch, M.

2016-06-15

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

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.

WE-D-BRB-03: Current State of Volumetric Image Guidance for Proton Therapy

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

Hua, C.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

WE-D-BRB-04: Clinical Applications of CBCT for Proton Therapy

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

Teo, B.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

WE-D-BRB-01: Basic Physics of Proton Therapy

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

Arjomandy, B.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

Low resolution 1H NMR assignment of proton populations in pound cake and its polymeric ingredients.

PubMed

Luyts, A; Wilderjans, E; Waterschoot, J; Van Haesendonck, I; Brijs, K; Courtin, C M; Hills, B; Delcour, J A

2013-08-15

Based on a model system approach, five different proton populations were distinguished in pound cake crumb using one dimensional low resolution (1)H NMR spectroscopy. In free induction decay (FID) measurements, proton populations were assigned to (i) non-exchanging CH protons of crystalline starch, proteins and crystalline fat and (ii) non-exchanging CH protons of amorphous starch and gluten, which are in little contact with water. In Carr-Purcell-Meiboom-Gill (CPMG) measurements, three proton populations were distinguished. The CPMG population with the lowest mobility and the FID population with the highest mobility represent the same proton population. The two CPMG proton populations with the highest mobility were assigned to exchanging protons (i.e., protons of water, starch, gluten, egg proteins and sugar) and protons of lipids (i.e., protons of egg yolk lipids and amorphous lipid fraction of margarine) respectively. Based on their spin-lattice relaxation times (T1), two dimensional (1)H NMR spectroscopy further resolved the two proton populations with the highest mobility into three and two proton populations, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Proton clouds to measure long-range contacts between nonexchangeable side chain protons in solid-state NMR.

PubMed

Sinnige, Tessa; Daniëls, Mark; Baldus, Marc; Weingarth, Markus

2014-03-26

We show that selective labeling of proteins with protonated amino acids embedded in a perdeuterated matrix, dubbed 'proton clouds', provides general access to long-range contacts between nonexchangeable side chain protons in proton-detected solid-state NMR, which is important to study protein tertiary structure. Proton-cloud labeling significantly improves spectral resolution by simultaneously reducing proton line width and spectral crowding despite a high local proton density in clouds. The approach is amenable to almost all canonical amino acids. Our method is demonstrated on ubiquitin and the β-barrel membrane protein BamA.

Proton-proton correlations observed in two-proton radioactivity of 94Ag.

PubMed

Mukha, Ivan; Roeckl, Ernst; Batist, Leonid; Blazhev, Andrey; Döring, Joachim; Grawe, Hubert; Grigorenko, Leonid; Huyse, Mark; Janas, Zenon; Kirchner, Reinhard; La Commara, Marco; Mazzocchi, Chiara; Tabor, Sam L; Van Duppen, Piet

2006-01-19

The stability and spontaneous decay of naturally occurring atomic nuclei have been much studied ever since Becquerel discovered natural radioactivity in 1896. In 1960, proton-rich nuclei with an odd or an even atomic number Z were predicted to decay through one- and two-proton radioactivity, respectively. The experimental observation of one-proton radioactivity was first reported in 1982, and two-proton radioactivity has now also been detected by experimentally studying the decay properties of 45Fe (refs 3, 4) and 54Zn (ref. 5). Here we report proton-proton correlations observed during the radioactive decay of a spinning long-lived state of the lightest known isotope of silver, 94Ag, which is known to undergo one-proton decay. We infer from these correlations that the long-lived state must also decay through simultaneous two-proton emission, making 94Ag the first nucleus to exhibit one- as well as two-proton radioactivity. We attribute the two-proton emission behaviour and the unexpectedly large probability for this decay mechanism to a very large deformation of the parent nucleus into a prolate (cigar-like) shape, which facilitates emission of protons either from the same or from opposite ends of the 'cigar'.

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.

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.

Restrained Proton Indicator in Combined Quantum-Mechanics/Molecular-Mechanics Dynamics Simulations of Proton Transfer through a Carbon Nanotube.

PubMed

Duster, Adam W; Lin, Hai

2017-09-14

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

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.

Characterizing the proton loading site in cytochrome c oxidase.

PubMed

Lu, Jianxun; Gunner, M R

2014-08-26

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

Characterizing the proton loading site in cytochrome c oxidase

PubMed Central

Lu, Jianxun; Gunner, M. R.

2014-01-01

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

Experimental observation of acoustic emissions generated by a pulsed proton beam from a hospital-based clinical cyclotron.

PubMed

Jones, Kevin C; Vander Stappen, François; Bawiec, Christopher R; Janssens, Guillaume; Lewin, Peter A; Prieels, Damien; Solberg, Timothy D; Sehgal, Chandra M; Avery, Stephen

2015-12-01

To measure the acoustic signal generated by a pulsed proton spill from a hospital-based clinical cyclotron. An electronic function generator modulated the IBA C230 isochronous cyclotron to create a pulsed proton beam. The acoustic emissions generated by the proton beam were measured in water using a hydrophone. The acoustic measurements were repeated with increasing proton current and increasing distance between detector and beam. The cyclotron generated proton spills with rise times of 18 μs and a maximum measured instantaneous proton current of 790 nA. Acoustic emissions generated by the proton energy deposition were measured to be on the order of mPa. The origin of the acoustic wave was identified as the proton beam based on the correlation between acoustic emission arrival time and distance between the hydrophone and proton beam. The acoustic frequency spectrum peaked at 10 kHz, and the acoustic pressure amplitude increased monotonically with increasing proton current. The authors report the first observation of acoustic emissions generated by a proton beam from a hospital-based clinical cyclotron. When modulated by an electronic function generator, the cyclotron is capable of creating proton spills with fast rise times (18 μs) and high instantaneous currents (790 nA). Measurements of the proton-generated acoustic emissions in a clinical setting may provide a method for in vivo proton range verification and patient monitoring.

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

Pion, Kaon, Proton and Antiproton Production in Proton-Proton Collisions

NASA Technical Reports Server (NTRS)

Norbury, John W.; Blattnig, Steve R.

2008-01-01

Inclusive pion, kaon, proton, and antiproton production from proton-proton collisions is studied at a variety of proton energies. Various available parameterizations of Lorentz-invariant differential cross sections as a function of transverse momentum and rapidity are compared with experimental data. The Badhwar and Alper parameterizations are moderately satisfactory for charged pion production. The Badhwar parameterization provides the best fit for charged kaon production. For proton production, the Alper parameterization is best, and for antiproton production the Carey parameterization works best. However, no parameterization is able to fully account for all the data.

MO-A-201-01: A Cliff’s Notes Version of Proton Therapy

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

Kruse, J.

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatchesmore » between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ from standard x-ray approaches, due to equipment design or the desire to maximize efficiency within a high-cost proton therapy treatment room. Differences between x-ray and proton therapy delivery will be described. Learning Objectives: Understand how CT HU are calibrated to provide proton stopping power, and the sources of uncertainty in this process. Understand why a PTV is not suitable for proton therapy, and how robust treatment planning and evaluation are used to mitigate uncertainties. Understand the source and implications of variable RBE in proton therapy Learn about proton specific challenges and approaches in beam delivery and image guidance Jon Kruse has a research grant from Varian Medical Systems related to proton therapy treatment plannning.; J. Kruse, Jon Kruse has a research grant with Varian Medical Systems related to proton therapy planning.« less

MO-A-201-00: A Cliff’s Notes Version of Proton Therapy

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

NONE

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatchesmore » between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ from standard x-ray approaches, due to equipment design or the desire to maximize efficiency within a high-cost proton therapy treatment room. Differences between x-ray and proton therapy delivery will be described. Learning Objectives: Understand how CT HU are calibrated to provide proton stopping power, and the sources of uncertainty in this process. Understand why a PTV is not suitable for proton therapy, and how robust treatment planning and evaluation are used to mitigate uncertainties. Understand the source and implications of variable RBE in proton therapy Learn about proton specific challenges and approaches in beam delivery and image guidance Jon Kruse has a research grant from Varian Medical Systems related to proton therapy treatment plannning.; J. Kruse, Jon Kruse has a research grant with Varian Medical Systems related to proton therapy planning.« less

F"orster-type mechanism of the redox-driven proton pump

NASA Astrophysics Data System (ADS)

Mourokh, Lev; Smirnov, Anatoly; Nori, Franco

2007-03-01

We propose a model to describe an electronically-driven proton pump in the cytochrome c oxidase (CcO). We examine the situation when the electron transport between the two sites embedded into the inner membrane of the mitochondrion occurs in parallel with the proton transfer from the protonable site that is close to the negative (inner) side of the membrane to the other protonable site located nearby the positive (outer) surface of the membrane. In addition to the conventional electron and proton tunnelings between the sites, the Coulomb interaction between electrons and protons localized on the corresponding sites leads to so-called F"orster transfer, i.e. to the process when the simultaneous electron and proton tunnelings are accompanied by the resonant energy transfer between the electrons and protons. Our calculations based on reasonable parameters have demonstrated that the F"orster process facilitates the proton pump at physiological temperatures. We have examined the effects of an electron voltage build-up, external temperature, and molecular electrostatics driving the electron and proton energies to the resonant conditions, and have shown that these parameters can control the proton pump operation.

Beam collimation and energy spectrum compression of laser-accelerated proton beams using solenoid field and RF cavity

NASA Astrophysics Data System (ADS)

Teng, J.; Gu, Y. Q.; Zhu, B.; Hong, W.; Zhao, Z. Q.; Zhou, W. M.; Cao, L. F.

2013-11-01

This paper presents a new method of laser produced proton beam collimation and spectrum compression using a combination of a solenoid field and a RF cavity. The solenoid collects laser-driven protons efficiently within an angle that is smaller than 12 degrees because it is mounted few millimeters from the target, and collimates protons with energies around 2.3 MeV. The collimated proton beam then passes through a RF cavity to allow compression of the spectrum. Particle-in-cell (PIC) simulations demonstrate the proton beam transport in the solenoid and RF electric fields. Excellent energy compression and collection efficiency of protons are presented. This method for proton beam optimization is suitable for high repetition-rate laser acceleration proton beams, which could be used as an injector for a conventional proton accelerator.

Experimental observation of acoustic emissions generated by a pulsed proton beam from a hospital-based clinical cyclotron

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

Jones, Kevin C.; Solberg, Timothy D.; Avery, Stephen, E-mail: Stephen.Avery@uphs.upenn.edu

Purpose: To measure the acoustic signal generated by a pulsed proton spill from a hospital-based clinical cyclotron. Methods: An electronic function generator modulated the IBA C230 isochronous cyclotron to create a pulsed proton beam. The acoustic emissions generated by the proton beam were measured in water using a hydrophone. The acoustic measurements were repeated with increasing proton current and increasing distance between detector and beam. Results: The cyclotron generated proton spills with rise times of 18 μs and a maximum measured instantaneous proton current of 790 nA. Acoustic emissions generated by the proton energy deposition were measured to be onmore » the order of mPa. The origin of the acoustic wave was identified as the proton beam based on the correlation between acoustic emission arrival time and distance between the hydrophone and proton beam. The acoustic frequency spectrum peaked at 10 kHz, and the acoustic pressure amplitude increased monotonically with increasing proton current. Conclusions: The authors report the first observation of acoustic emissions generated by a proton beam from a hospital-based clinical cyclotron. When modulated by an electronic function generator, the cyclotron is capable of creating proton spills with fast rise times (18 μs) and high instantaneous currents (790 nA). Measurements of the proton-generated acoustic emissions in a clinical setting may provide a method for in vivo proton range verification and patient monitoring.« less

Gluonic hot spots and spatial correlations inside the proton

NASA Astrophysics Data System (ADS)

Albacete, Javier L.; Petersen, Hannah; Soto-Ontoso, Alba

2017-11-01

In this work, largely based on [J. L. Albacete, A. Soto-Ontoso, Hot spots and the hollowness of proton-proton interactions at high energies, arXiv:1605.09176; J. L. Albacete, H. Petersen, A. Soto-Ontoso, Correlated wounded hot spots in proton-proton interactions, arXiv:1612.06274], we present a novel initial state geometry for proton-proton interactions. We rely on gluonic hot spots as effective degrees of freedom whose transverse positions inside the proton are correlated. We explore the impact of these non-trivial spatial correlations on the eccentricity and triangularity of the system following a Monte Carlo Glauber approach.

Classical Molecular Dynamics with Mobile Protons.

PubMed

Lazaridis, Themis; Hummer, Gerhard

2017-11-27

An important limitation of standard classical molecular dynamics simulations is the inability to make or break chemical bonds. This restricts severely our ability to study processes that involve even the simplest of chemical reactions, the transfer of a proton. Existing approaches for allowing proton transfer in the context of classical mechanics are rather cumbersome and have not achieved widespread use and routine status. Here we reconsider the combination of molecular dynamics with periodic stochastic proton hops. To ensure computational efficiency, we propose a non-Boltzmann acceptance criterion that is heuristically adjusted to maintain the correct or desirable thermodynamic equilibria between different protonation states and proton transfer rates. Parameters are proposed for hydronium, Asp, Glu, and His. The algorithm is implemented in the program CHARMM and tested on proton diffusion in bulk water and carbon nanotubes and on proton conductance in the gramicidin A channel. Using hopping parameters determined from proton diffusion in bulk water, the model reproduces the enhanced proton diffusivity in carbon nanotubes and gives a reasonable estimate of the proton conductance in gramicidin A.

Mammalian complex I pumps 4 protons per 2 electrons at high and physiological proton motive force in living cells.

PubMed

Ripple, Maureen O; Kim, Namjoon; Springett, Roger

2013-02-22

Mitochondrial complex I couples electron transfer between matrix NADH and inner-membrane ubiquinone to the pumping of protons against a proton motive force. The accepted proton pumping stoichiometry was 4 protons per 2 electrons transferred (4H(+)/2e(-)) but it has been suggested that stoichiometry may be 3H(+)/2e(-) based on the identification of only 3 proton pumping units in the crystal structure and a revision of the previous experimental data. Measurement of proton pumping stoichiometry is challenging because, even in isolated mitochondria, it is difficult to measure the proton motive force while simultaneously measuring the redox potentials of the NADH/NAD(+) and ubiquinol/ubiquinone pools. Here we employ a new method to quantify the proton motive force in living cells from the redox poise of the bc(1) complex measured using multiwavelength cell spectroscopy and show that the correct stoichiometry for complex I is 4H(+)/2e(-) in mouse and human cells at high and physiological proton motive force.

200 MeV Proton Radiography Studies with a Hand Phantom Using a Prototype Proton CT Scanner

PubMed Central

Plautz, Tia; Bashkirov, V.; Feng, V.; Hurley, F.; Johnson, R.P.; Leary, C.; Macafee, S.; Plumb, A.; Rykalin, V.; Sadrozinski, H.F.-W.; Schubert, K.; Schulte, R.; Schultze, B.; Steinberg, D.; Witt, M.; Zatserklyaniy, A.

2014-01-01

Proton radiography has applications in patient alignment and verification procedures for proton beam radiation therapy. In this paper, we report an experiment which used 200 MeV protons to generate proton energy-loss and scattering radiographs of a hand phantom. The experiment used the first-generation proton CT scanner prototype, which was installed on the research beam line of the clinical proton synchrotron at Loma Linda University Medical Center (LLUMC). It was found that while both radiographs displayed anatomical details of the hand phantom, the energy-loss radiograph had a noticeably higher resolution. Nonetheless, scattering radiography may yield more contrast between soft and bone tissue than energy-loss radiography, however, this requires further study. This study contributes to the optimization of the performance of the next-generation of clinical proton CT scanners. Furthermore, it demonstrates the potential of proton imaging (proton radiography and CT), which is now within reach of becoming available as a new, potentially low-dose medical imaging modality. PMID:24710156

Nanoscale measurements of proton tracks using fluorescent nuclear track detectors

PubMed Central

Sawakuchi, Gabriel O.; Ferreira, Felisberto A.; McFadden, Conor H.; Hallacy, Timothy M.; Granville, Dal A.; Sahoo, Narayan; Akselrod, Mark S.

2016-01-01

Purpose: The authors describe a method in which fluorescence nuclear track detectors (FNTDs), novel track detectors with nanoscale spatial resolution, are used to determine the linear energy transfer (LET) of individual proton tracks from proton therapy beams by allowing visualization and 3D reconstruction of such tracks. Methods: FNTDs were exposed to proton therapy beams with nominal energies ranging from 100 to 250 MeV. Proton track images were then recorded by confocal microscopy of the FNTDs. Proton tracks in the FNTD images were fit by using a Gaussian function to extract fluorescence amplitudes. Histograms of fluorescence amplitudes were then compared with LET spectra. Results: The authors successfully used FNTDs to register individual proton tracks from high-energy proton therapy beams, allowing reconstruction of 3D images of proton tracks along with delta rays. The track amplitudes from FNTDs could be used to parameterize LET spectra, allowing the LET of individual proton tracks from therapeutic proton beams to be determined. Conclusions: FNTDs can be used to directly visualize proton tracks and their delta rays at the nanoscale level. Because the track intensities in the FNTDs correlate with LET, they could be used further to measure LET of individual proton tracks. This method may be useful for measuring nanoscale radiation quantities and for measuring the LET of individual proton tracks in radiation biology experiments. PMID:27147359

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.

Nanoscale measurements of proton tracks using fluorescent nuclear track detectors

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

Sawakuchi, Gabriel O., E-mail: gsawakuchi@mdanderson.org; Sahoo, Narayan; Ferreira, Felisberto A.

Purpose: The authors describe a method in which fluorescence nuclear track detectors (FNTDs), novel track detectors with nanoscale spatial resolution, are used to determine the linear energy transfer (LET) of individual proton tracks from proton therapy beams by allowing visualization and 3D reconstruction of such tracks. Methods: FNTDs were exposed to proton therapy beams with nominal energies ranging from 100 to 250 MeV. Proton track images were then recorded by confocal microscopy of the FNTDs. Proton tracks in the FNTD images were fit by using a Gaussian function to extract fluorescence amplitudes. Histograms of fluorescence amplitudes were then compared withmore » LET spectra. Results: The authors successfully used FNTDs to register individual proton tracks from high-energy proton therapy beams, allowing reconstruction of 3D images of proton tracks along with delta rays. The track amplitudes from FNTDs could be used to parameterize LET spectra, allowing the LET of individual proton tracks from therapeutic proton beams to be determined. Conclusions: FNTDs can be used to directly visualize proton tracks and their delta rays at the nanoscale level. Because the track intensities in the FNTDs correlate with LET, they could be used further to measure LET of individual proton tracks. This method may be useful for measuring nanoscale radiation quantities and for measuring the LET of individual proton tracks in radiation biology experiments.« less

Time latencies of Helicobacter pylori eradication after peptic ulcer and risk of recurrent ulcer, ulcer adverse events, and gastric cancer: a population-based cohort study.

PubMed

Sverdén, Emma; Brusselaers, Nele; Wahlin, Karl; Lagergren, Jesper

2017-12-09

Helicobacter pylori is associated with peptic ulcer disease and gastric cancer. Therefore we wanted to test how various lengths of delays in H pylori eradication therapy influence the risk of recurrent peptic ulcer, ulcer adverse events, and gastric cancer. This population-based nationwide Swedish cohort study included 29,032 patients receiving H pylori eradication therapy after peptic ulcer disease in 2005 to 2013. Predefined time intervals between date of peptic ulcer diagnosis and date of eradication therapy were analyzed in relation to study outcomes. Cox regression provided hazard ratios (HRs) and 95% confidence intervals (95% CIs), adjusted for age, sex, comorbidity, history of ulcer disease, use of ulcerogenic drugs, and use of proton pump inhibitors (PPIs). Compared with eradication therapy within 7 days of peptic ulcer diagnosis, eradication therapy within 8 to 30, 31 to 60, 61 to 365, and >365 days corresponded with HRs of recurrent ulcer of 1.17 (95% CI, 1.08-1.25), 2.37 (95% CI, 2.16-2.59), 2.96 (95% CI, 2.76-3.16), and 3.55 (95% CI, 3.33-3.79), respectively. The corresponding HRs for complicated ulcer were 1.55 (95% CI, 1.35-1.78), 3.19 (95% CI, 2.69-3.78), 4.00 (95% CI, 3.51-4.55), and 6.14, (95% CI, 5.47-6.89), respectively. For gastric cancer the corresponding HRs were .85 (95% CI, .32-2.23), 1.31 (95% CI, .31-5.54), 3.64 (95% CI, 1.55-8.56), and 4.71 (95% CI, 2.36-9.38), respectively. Delays in H pylori eradication therapy after peptic ulcer diagnosis time-dependently increase the risk of recurrent ulcer, even more so for complicated ulcer, starting from delays of 8 to 30 days. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Gamma-Ray Observations Related to the Acceleration of Ions in the Corona

NASA Astrophysics Data System (ADS)

Share, G. H.; Murphy, R. J.; Tolbert, A. K.; White, S. M.; Dennis, B. R.; Schwartz, R. A.; Tylka, A. J.

2016-12-01

High-energy gamma-rays associated with solar flares have been observed for over thirty-five years by various satellite experiments. The most sensitive observations have been made recently by the Large Area Telescope (LAT) experiment on the Fermi satellite. These observations confirm the earlier observations in which >100 MeV emission was detected coincident with the impulsive flare hard X-rays and also in the minutes and hours afterward. Spectral evidence from the largest of these latter, time-extended events, indicate they arise from the decay of neutral and charged pions produced by the interaction of protons and alpha particles with energies >300 MeV/nucl and >200 MeV/nucl, respectively. These high-energy time-extended events, are almost always associated with fast CME's and appear to begin from as short as 1 min to as long as 100 min after the onset of the CME. The events appear to last as short as 10 min to as long as 18 hr. Our analysis indicates that the number of >500 MeV protons producing the time-extended emission typically is an order magnitude larger than the number producing emission during the impulsive flare. The observed delays from the CME and energetic comparisons suggest that most of the energy in the ions producing the sustained time-extended emission came from a source other than the impulsive flare. It is likely that the particles were accelerated by shocks associated with the CME's and thus may have an origin common with SEPs observed in space. Our comparisons using GOES HEPAD and neutron monitor data, and those reported in this Session by DeNolfo et al. using data from PAMELA, suggest that the numbers of particles producing the gamma-ray emission are typically at least an order of magnitude smaller than those observed in space. We focus our discussion in this talk on the time-extended gamma-ray events that begin within minutes of the CME onset as they may reflect shock-acceleration of protons to hundreds of MeV deep in the corona. This work was supported by the SHINE/NSF, NASA Fermi GI and SR&T, Chief of Naval Research, and EU HESPERIA programs.

Photodiode radiation hardness, lyman-alpha emitting galaxies and photon detection in liquid argon neutrino detectors

NASA Astrophysics Data System (ADS)

Baptista, Brian

2013-12-01

My dissertation is comprised of three projects: 1) studies of Lyman-alpha Emitting galaxies (LAEs), 2) radiation hardness studies of InGaAs photodiodes (PDs), and 3) scintillation photon detection in liquid argon (LAr) neutrino detectors. I began work on the project that has now become WFIRST, developing a science case that would use WFIRST after launch for the observation of LAEs. The radiation hardness of PDs was as an effort to support the WFIRST calibration team. When WFIRST was significantly delayed, I joined an R&D effort that applied my skills to work on photon detection in LAr neutrino detectors. I report results on a broadband selection method developed to detect high equivalent width (EW) LAEs. Using photometry from the CFHT-Legacy Survey Deep 2 and 3 fields, I have spectroscopically confirmed 63 z=2.5-3.5 LAEs using the WIYN/Hydra spectrograph. Using UV continuum-fitting techniques I computed properties such as EWs, internal reddening and star formation rates. 62 of my LAEs show evidence to be normal dust-free LAEs. Second, I present an investigation into the effects of ionizing proton radiation on commercial off-the-shelf InGaAs PDs. I developed a monochromator-based test apparatus that utilized NIST-calibrated reference PDs. I tested the PDs for changes to their dark current, relative responsivity as a function of wavelength, and absolute responsivity. I irradiated the test PDs using 30, 52, and 98 MeV protons at the IU Cyclotron Facility. I found the InGaAs PDs showed increased dark current as the fluence increased with no evidence of broadband response degradation at the fluences expected at an L2 orbit and a 10-year mission lifetime. Finally, I detail my efforts on technology development of both optical detector technologies and waveshifting light guide construction for LAr vacuum UV scintillation light. Cryogenic neutrino detectors use photon detection for both accelerator based science and for SNe neutrino detection and proton decay. I have developed waveshifter doped cast acrylic light guides that convert scintillation light and guide the waveshifted light to SiPMs detectors.

Structural and pH Dependence of Excited State PCET Reactions Involving Reductive Quenching of the MLCT Excited State of [Ru II(bpy) 2(bpz)] 2+ by Hydroquinones

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

Lebedeva, Natalia V.; Schmidt, Robert D.; Concepcion, Javier J.

2011-01-01

The proton-coupled electron transfer (PCET) reaction between the bpz-based photoexcited ³MLCT state of [Ru II(bpy) 2(bpz)] 2+ (bpy = 2,2'-bipyridine, bpz = 2,2'-bipyrazine) and a series of substituted hydroquinones (H₂Q) has been studied by transient absorption (TA) and time-resolved electron paramagnetic resonance (TREPR) spectroscopy at X-band. When the reaction is carried out in a CH₃CN/H₂O mixed solvent system with unsubstituted hydroquinone, the neutral semiquinone radical (4a) and its conjugate base, the semiquinone radical anion (4b), are both observed. Variation of the acid strength in the solvent mixture allows the acid/base dependence of the PCET reaction to be investigated. In solutionsmore » with very low acid concentrations, TREPR spectra exclusively derived from radical anion 4b are observed, while at very high acid concentrations, the spectrum is assigned to the protonated structure 4a. At intermediate acid concentrations, either a superposition of spectra is observed (slow exchange between 4a and 4b) or substantial broadening in the TREPR spectrum is observed (fast exchange between 4a and 4b). Variation of substituents on the H₂Q ring substantially alter this acid/base dependence and provide a means to investigate electronic effects on both the ET and PT components of the PCET process. The TA results suggest a change in mechanism from PCET to direct ET quenching in strongly basic solutions and with electron withdrawing groups on the H₂Q ring system. Changing the ligand on the Ru complex also alters the acid/base dependence of the TREPR spectra through a series of complex equilibria between protonated and deprotonated hydroquinone radicals and anions. The relative intensities of the signals from radical 4a versus 4b can be rationalized quantitatively in terms of these equilibria and the relevant pK{sub a} values. An observed equilibrium deuterium isotope effect supports the conclusion that the post-PCET HQ •/Q •- equilibrium is the most important in determining the 4a/4b ratio at early delay times.« less

Organic solute changes with acidification in Lake Skjervatjern as shown by 1H-NMR spectroscopy

USGS Publications Warehouse

Malcolm, R.L.; Hayes, T.

1994-01-01

1H-NMR spectroscopy has been found to be a useful tool to establish possible real differences and trends between all natural organic solute fractions (fulvic acids, humic acids, and XAD-4 acids) after acid-rain additions to the Lake Skjervatjern watershed. The proton NMR technique used in this study determined the spectral distribution of nonexchangeable protons among four peaks (aliphatic protons; aliphatic protons on carbon ?? or attached to electronegative groups; protons on carbons attached to O or N heteroatoms; and aromatic protons). Differences of 10% or more in the respective peak areas were considered to represent a real difference. After one year of acidification, fulvic acids decreased 13% (relative) in Peak 3 protons on carbon attached to N and O heteratoms and exhibited a decrease in aromatic protons between 27% and 31%. Humic acids also exhibited an 11% relative decrease in aromatic protons as a result of acidification. After one year of acidification, real changes were shown in three of the four proton assignments in XAD-4 acids. Peak 1 aliphatic protons increased by 14% (relative), Peak 3 protons on carbons attached to O and N heteroatoms decreased by 13% (relative), and aromatic protons (Peak 4) decreased by 35% (relative). Upon acidification, there was a trend in all solutes for aromatic protons to decrease and aliphatic protons to increase. The natural variation in organic solutes as shown in the Control Side B of the lake from 1990 to 1991 is perhaps a small limitation to the same data interpretations of acid rain changes at the Lake Skjervatjern site, but the proton NMR technique shows great promise as an independent scientific tool to detect and support other chemical techniques in establishing organic solute changes with different treatments (i.e., additions of acid rain).

Surface proton transport of fully protonated poly(aspartic acid) thin films on quartz substrates

NASA Astrophysics Data System (ADS)

Nagao, Yuki; Kubo, Takahiro

2014-12-01

Thin film structure and the proton transport property of fully protonated poly(aspartic acid) (P-Asp100) have been investigated. An earlier study assessed partially protonated poly(aspartic acid), highly oriented thin film structure and enhancement of the internal proton transport. In this study of P-Asp100, IR p-polarized multiple-angle incidence resolution (P-MAIR) spectra were measured to investigate the thin film structure. The obtained thin films, with thicknesses of 120-670 nm, had no oriented structure. Relative humidity dependence of the resistance, proton conductivity, and normalized resistance were examined to ascertain the proton transport property of P-Asp100 thin films. The obtained data showed that the proton transport of P-Asp100 thin films might occur on the surface, not inside of the thin film. This phenomenon might be related with the proton transport of the biological system.

Monitoring of monocyte recruitment in reperfused myocardial infarction with intramyocardial hemorrhage and microvascular obstruction by combined fluorine 19 and proton cardiac magnetic resonance imaging.

PubMed

Ye, Yu-Xiang; Basse-Lüsebrink, Thomas C; Arias-Loza, Paula-Anahi; Kocoski, Vladimir; Kampf, Thomas; Gan, Qiang; Bauer, Elisabeth; Sparka, Stefanie; Helluy, Xavier; Hu, Kai; Hiller, Karl-Heinz; Boivin-Jahns, Valerie; Jakob, Peter M; Jahns, Roland; Bauer, Wolfgang R

2013-10-22

Monocytes and macrophages are indispensable in the healing process after myocardial infarction (MI); however, the spatiotemporal distribution of monocyte infiltration and its correlation to prognostic indicators of reperfused MI have not been well described. With combined fluorine 19/proton ((1)H) magnetic resonance imaging, we noninvasively visualized the spatiotemporal recruitment of monocytes in vivo in a rat model of reperfused MI. Blood monocytes were labeled by intravenous injection of (19)F-perfluorocarbon emulsion 1 day after MI. The distribution patterns of monocyte infiltration were correlated to the presence of microvascular obstruction (MVO) and intramyocardial hemorrhage. In vivo, (19)F/(1)H magnetic resonance imaging performed in series revealed that monocyte infiltration was spatially inhomogeneous in reperfused MI areas. In the absence of MVO, monocyte infiltration was more intense in MI regions with serious ischemia-reperfusion injuries, indicated by severe intramyocardial hemorrhage; however, monocyte recruitment was significantly impaired in MVO areas accompanied by severe intramyocardial hemorrhage. Compared with MI with isolated intramyocardial hemorrhage, MI with MVO resulted in significantly worse pump function of the left ventricle 28 days after MI. Monocyte recruitment was inhomogeneous in reperfused MI tissue. It was highly reduced in MVO areas defined by magnetic resonance imaging. The impaired monocyte infiltration in MVO regions could be related to delayed healing and worse functional outcomes in the long term. Therefore, monocyte recruitment in MI with MVO could be a potential diagnostic and therapeutic target that could be monitored noninvasively and longitudinally by (19)F/(1)H magnetic resonance imaging in vivo.

Second harmonic poloidal waves observed by Van Allen Probes in the dusk-midnight sector

DOE PAGES

Min, Kyungguk; Takahashi, Kazue; Ukhorskiy, Aleksandr Y.; ...

2017-02-24

This paper presents observations of ultralow-frequency (ULF) waves from Van Allen Probes. The event that generated the ULF waves occurred 2 days after a minor geomagnetic storm during a geomagnetically quiet time. Narrowband pulsations with a frequency of about 7 mHz with moderate amplitudes were registered in the premidnight sector when Probe A was passing through an enhanced density region near geosynchronous orbit. Probe B, which passed through the region earlier, did not detect the narrowband pulsations but only broadband noise. Despite the single-spacecraft measurements, we were able to determine various wave properties. We find that the observed waves aremore » a second harmonic poloidal mode propagating westward with an azimuthal wave number estimated to be ~100; the magnetic field fluctuations have a finite compressional component due to small but finite plasma beta (~0.1); the energetic proton fluxes in the energy ranging from above 10 keV to about 100 keV exhibit pulsations with the same frequency as the poloidal mode and energy-dependent phase delays relative to the azimuthal component of the electric field, providing evidence for drift-bounce resonance; and the second harmonic poloidal mode may have been excited via the drift-bounce resonance mechanism with free energy fed by the inward radial gradient of ~80 keV protons. Here, we show that the wave active region is where the plume overlaps the outer edge of ring current and suggest that this region can have a wide longitudinal extent near geosynchronous orbit.« less

Second harmonic poloidal waves observed by Van Allen Probes in the dusk-midnight sector

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

Min, Kyungguk; Takahashi, Kazue; Ukhorskiy, Aleksandr Y.

This paper presents observations of ultralow-frequency (ULF) waves from Van Allen Probes. The event that generated the ULF waves occurred 2 days after a minor geomagnetic storm during a geomagnetically quiet time. Narrowband pulsations with a frequency of about 7 mHz with moderate amplitudes were registered in the premidnight sector when Probe A was passing through an enhanced density region near geosynchronous orbit. Probe B, which passed through the region earlier, did not detect the narrowband pulsations but only broadband noise. Despite the single-spacecraft measurements, we were able to determine various wave properties. We find that the observed waves aremore » a second harmonic poloidal mode propagating westward with an azimuthal wave number estimated to be ~100; the magnetic field fluctuations have a finite compressional component due to small but finite plasma beta (~0.1); the energetic proton fluxes in the energy ranging from above 10 keV to about 100 keV exhibit pulsations with the same frequency as the poloidal mode and energy-dependent phase delays relative to the azimuthal component of the electric field, providing evidence for drift-bounce resonance; and the second harmonic poloidal mode may have been excited via the drift-bounce resonance mechanism with free energy fed by the inward radial gradient of ~80 keV protons. Here, we show that the wave active region is where the plume overlaps the outer edge of ring current and suggest that this region can have a wide longitudinal extent near geosynchronous orbit.« less

Progress in proton-detected solid-state NMR (SSNMR): Super-fast 2D SSNMR collection for nano-mole-scale proteins

NASA Astrophysics Data System (ADS)

Ishii, Yoshitaka; Wickramasinghe, Ayesha; Matsuda, Isamu; Endo, Yuki; Ishii, Yuji; Nishiyama, Yusuke; Nemoto, Takahiro; Kamihara, Takayuki

2018-01-01

Proton-detected solid-state NMR (SSNMR) spectroscopy has attracted much attention due to its excellent sensitivity and effectiveness in the analysis of trace amounts of amyloid proteins and other important biological systems. In this perspective article, we present the recent sensitivity limit of 1H-detected SSNMR using "ultra-fast" magic-angle spinning (MAS) at a spinning rate (νR) of 80-100 kHz. It was demonstrated that the high sensitivity of 1H-detected SSNMR at νR of 100 kHz and fast recycling using the paramagnetic-assisted condensed data collection (PACC) approach permitted "super-fast" collection of 1H-detected 2D protein SSNMR. A 1H-detected 2D 1H-15N correlation SSNMR spectrum for ∼27 nmol of a uniformly 13C- and 15N-labeled GB1 protein sample in microcrystalline form was acquired in only 9 s with 50% non-uniform sampling and short recycle delays of 100 ms. Additional data suggests that it is now feasible to detect as little as 1 nmol of the protein in 5.9 h by 1H-detected 2D 1H-15N SSNMR at a nominal signal-to-noise ratio of five. The demonstrated sensitivity is comparable to that of modern solution protein NMR. Moreover, this article summarizes the influence of ultra-fast MAS and 1H-detection on the spectral resolution and sensitivity of protein SSNMR. Recent progress in signal assignment and structural elucidation by 1H-detected protein SSNMR is outlined with both theoretical and experimental aspects.

Implications of the pion-decay gamma emission and neutron observations with CORONAS-F/SONG

NASA Astrophysics Data System (ADS)

Kurt, V.; Yushkov, B.; Kudela, K.

2013-05-01

We analyzed the high-energy gamma and neutron emissions observed by the SONG instrument onboard the CORONAS-F satellite during August 25, 2001, October 28, 2003, November 4, 2003, and January 20, 2005 solar flares. These flares produced neutrons and/or protons recorded near Earth. The SONG response was consistent with detection of the pion-decay gamma emission and neutrons in these events. We compared time profiles of various electromagnetic emissions and showed that the maximum of the pion-decay-emission coincided in time best of all with the soft X-ray derivative, dISXR/dt, maximum. We evaluated the energy of accelerated ions and compared it with the energy deposited by accelerated electrons. The ion energy becomes comparable or even higher than the electron energy from a certain step of flare development. So the time profile of dISXR/dt is a superposition of energy deposited by both fractions of accelerated particles. This result allowed us to use a time profile of dISXR/dt as a real proxy of time behavior of the energy release at least during major flare analysis. In particular the time interval when the dISXR/dt value exceeds 0.9 of its maximum can be used as a unified reference point for the calculations of time delay between the high-energy proton acceleration and GLE onset. Analysis of the total set of pion-decay emission observations shows that such temporal closeness of pion-decay emission maximum and the soft X-ray derivative maximum is typical but not obligatory.

Proton transfer events in GFP.

PubMed

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

2011-09-28

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

Studies of Water V. Five Phonons in Protonic Semiconductor Lattice Model of Pure Liquid Water

NASA Astrophysics Data System (ADS)

Jie, Binbin; Sah, Chihtang

2017-07-01

We report physics based confirmation (~1% RMS deviation), by existing experimental data, of proton-prohol (proton-hole) ion product (pH) and mobilities in pure liquid water (0-100{}{{o}}C, 1-atm pressure) anticipated from our melted-ice Hexagonal-Close-Packed (H{}2O){}4 Lattice Model. Five phonons are identified. (1) A propagating protonic phonon (520.9 meV from lone-pair-blue-shifted stretching mode of isolated water molecule) absorbed to generate a proton-prohol pair or detrap a tightly-bound proton. (2) Two (173.4 and 196.6 meV) bending-breathing protonic-proholic or protonic phonons absorbed during de-trapping-limited proton or proton-prohol mobilities. (3) Two propagating oxygenic-wateric Debye-Dispersive phonons (30.3 and 27.5 meV) absorbed during scattering-limited proton or proton-prohol mobilities. Summer School in Theoretical Physics funded by the National Natural Science Foundation of China, on Soft Materials Physics, hosted by the Physics Department of Xiamen University, China, during August 1 to 14, 2016. This was also just presented at the 2017 March Meeting (March 14 to 16) of the American Physical Society in New Orleans, USA.

Proton therapy in the clinic.

PubMed

DeLaney, Thomas F

2011-01-01

The clinical advantage for proton radiotherapy over photon approaches is the marked reduction in integral dose to the patient, due to the absence of exit dose beyond the proton Bragg peak. The integral dose with protons is approximately 60% lower than that with any external beam photon technique. Pediatric patients, because of their developing normal tissues and anticipated length of remaining life, are likely to have the maximum clinical gain with the use of protons. Proton therapy may also allow treatment of some adult tumors to much more effective doses, because of normal tissue sparing distal to the tumor. Currently, the most commonly available proton treatment technology uses 3D conformal approaches based on (a) distal range modulation, (b) passive scattering of the proton beam in its x- and y-axes, and (c) lateral beam-shaping. It is anticipated that magnetic pencil beam scanning will become the dominant mode of proton delivery in the future, which will lower neutron scatter associated with passively scattered beam lines, reduce the need for expensive beam-shaping devices, and allow intensity-modulated proton radiotherapy. Proton treatment plans are more sensitive to variations in tumor size and normal tissue changes over the course of treatment than photon plans, and it is expected that adaptive radiation therapy will be increasingly important for proton therapy as well. While impressive treatment results have been reported with protons, their cost is higher than for photon IMRT. Hence, protons should ideally be employed for anatomic sites and tumors not well treated with photons. While protons appear cost-effective for pediatric tumors, their cost-effectiveness for treatment of some adult tumors, such as prostate cancer, is uncertain. Comparative studies have been proposed or are in progress to more rigorously assess their value for a variety of sites. The utility of proton therapy will be enhanced by technological developments that reduce its cost. Combinations of 3D protons with IMRT photons may offer improved treatment plans at lower cost than pure proton plans. Hypofractionation with proton therapy appears to be safe and cost-effective for many tumor sites, such as for selected liver, lung and pancreas cancers, and may yield significant reduction in the cost of a therapy course. Together, these offer practical strategies for expanding the clinical availability of proton therapy. Copyright © 2011 S. Karger AG, Basel.

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.

Influence of the Selectivity Filter Properties on Proton Selectivity in the Influenza A M2 Channel.

PubMed

Dudev, Todor; Grauffel, Cédric; Lim, Carmay

2016-10-05

The homotetrameric M2 proton channel of influenza A plays a crucial role in the viral life cycle and is thus an important therapeutic target. It selectively conducts protons against a background of other competing cations whose concentrations are up to a million times greater than the proton concentration. Its selectivity is largely determined by a constricted region of its open pore known as the selectivity filter, which is lined by four absolutely conserved histidines. While the mechanism of proton transport through the channel has been studied, the physical principles underlying the selectivity for protons over other cations in the channel's His 4 selectivity filter remain elusive. Furthermore, it is not known if proton selectivity absolutely requires all four histidines with two of the four histidines protonated and if other titratable amino acid residues in lieu of the histidines could bind protons and how they affect proton selectivity. Here, we elucidate how the competition between protons and rival cations such as Na + depends on the selectivity filter's (1) histidine protonation state, (2) solvent exposure, (3) oligomeric state (the number of protein chains and thus the number of His ligands), and (4) ligand composition by evaluating the free energies for replacing monovalent Na + with H 3 O + in various model selectivity filters. We show that tetrameric His 4 filters are more proton-selective than their trimeric His 3 counterparts, and a dicationic His 4 filter where two of the four histidines are protonated is more proton-selective than tetrameric filters with other charge states/composition (different combinations of His protonation states or different metal-ligating ligands). The [His 4 ] 2+ filter achieves proton selectivity by providing suboptimal binding conditions for rival cations such as Na + , which prefers a neutral or negatively charged filter instead of a dicationic one, and three rather than four ligands with oxygen-ligating atoms.

SU-F-J-56: The Connection Between Cherenkov Light Emission and Radiation Absorbed Dose in Proton Irradiated Phantoms

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

Darafsheh, A; Kassaee, A; Finlay, J

Purpose: Range verification in proton therapy is of great importance. Cherenkov light follows the photon and electron energy deposition in water phantom. The purpose of this study is to investigate the connection between Cherenkov light generation and radiation absorbed dose in a water phantom irradiated with proton beams. Methods: Monte Carlo simulation was performed by employing FLUKA Monte Carlo code to stochastically simulate radiation transport, ionizing radiation dose deposition, and Cherenkov radiation in water phantoms. The simulations were performed for proton beams with energies in the range 50–600 MeV to cover a wide range of proton energies. Results: The mechanismmore » of Cherenkov light production depends on the initial energy of protons. For proton energy with 50–400 MeV energy that is below the threshold (∼483 MeV in water) for Cherenkov light production directly from incident protons, Cherenkov light is produced mainly from the secondary electrons liberated as a result of columbic interactions with the incident protons. For proton beams with energy above 500 MeV, in the initial depth that incident protons have higher energy than the Cherenkov light production threshold, the light has higher intensity. As the slowing down process results in lower energy protons in larger depths in the water phantom, there is a knee point in the Cherenkov light curve vs. depth due to switching the Cherenkov light production mechanism from primary protons to secondary electrons. At the end of the depth dose curve the Cherenkov light intensity does not follow the dose peak because of the lack of high energy protons to produce Cherenkov light either directly or through secondary electrons. Conclusion: In contrast to photon and electron beams, Cherenkov light generation induced by proton beams does not follow the proton energy deposition specially close to the end of the proton range near the Bragg peak.« less

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.

Proton elastic scattering from stable and unstable nuclei - Extraction of nuclear densities

NASA Astrophysics Data System (ADS)

Sakaguchi, H.; Zenihiro, J.

2017-11-01

Progress in proton elastic scattering at intermediate energies to determine nuclear density distributions is reviewed. After challenges of about 15 years to explain proton elastic scattering and associated polarization phenomena at intermediate energies, we have reached to some conclusions regarding proton elastic scattering as a means of obtaining nuclear densities. During this same period, physics of unstable nuclei has become of interest, and the density distributions of protons and neutrons play more important roles in unstable nuclei, since the differences in proton and neutron numbers and densities are expected to be significant. As such, proton elastic scattering experiments at intermediate energies using the inverse kinematic method have started to determine density distributions of unstable nuclei. In the region of unstable nuclei, we are confronted with a new problem when attempting to find proton and neutron densities separately from elastic proton scattering data, since electron scattering data for unstable nuclei are not presently available. We introduce a new means of determining proton and neutron densities separately by double-energy proton elastic scattering at intermediate energies.

Mammalian Complex I Pumps 4 Protons per 2 Electrons at High and Physiological Proton Motive Force in Living Cells*

PubMed Central

Ripple, Maureen O.; Kim, Namjoon; Springett, Roger

2013-01-01

Mitochondrial complex I couples electron transfer between matrix NADH and inner-membrane ubiquinone to the pumping of protons against a proton motive force. The accepted proton pumping stoichiometry was 4 protons per 2 electrons transferred (4H+/2e−) but it has been suggested that stoichiometry may be 3H+/2e− based on the identification of only 3 proton pumping units in the crystal structure and a revision of the previous experimental data. Measurement of proton pumping stoichiometry is challenging because, even in isolated mitochondria, it is difficult to measure the proton motive force while simultaneously measuring the redox potentials of the NADH/NAD+ and ubiquinol/ubiquinone pools. Here we employ a new method to quantify the proton motive force in living cells from the redox poise of the bc1 complex measured using multiwavelength cell spectroscopy and show that the correct stoichiometry for complex I is 4H+/2e− in mouse and human cells at high and physiological proton motive force. PMID:23306206

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.

Development of a Multileaf Collimator for Proton Radiotherapy

DTIC Science & Technology

2007-06-01

for proton radiotherapy, and the first year of the project to develop image guided treatment protocols for proton therapy . This research...multileaf collimator (MLC) for proton therapy and investigates the issues that must be resolved to use an MLC in proton therapy . The second technology...the contract included three development agreements directly related to the work supported by this grant to develop technology for proton therapy .

Proton-Proton Scattering at 105 Mev and 75 Mev

DOE R&D Accomplishments Database

Birge, R. W.; Kruse, U. E.; Ramsey, N. F.

1951-01-31

The scattering of protons by protons provides an important method for studying the nature of nuclear forces. Recent proton-proton scattering experiments at energies as high as thirty Mev{sup 1} have failed to show any appreciable contribution to the cross section from higher angular momentum states, but it is necessary to bring in tensor forces to explain the magnitude of the observed cross section.

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

PubMed

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

2015-06-04

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

Identifying the proton transfer reaction mechanism via a proton-bound dimeric intermediate for esomeprazoles by a kinetic method combined with density functional theory calculations.

PubMed

Cao, Xiaoji; Zhang, Feifei; Zhu, Kundan; Ye, Xuemin; Shen, Lingxiao; Chen, Jiaoyu; Mo, Weimin

2014-05-15

Esomeprazole analogs are a class of important proton pump inhibitors for the treatment of gastro-esophageal reflux diseases. Understanding the fragmentation reaction mechanism of the protonated esomeprazole analogs will facilitate the characterization of their complex metabolic fate in humans. In this paper, the kinetic method and theoretical calculations were applied to evaluate the fragmentation of protonated esomeprazole analogs. All collision-induced dissociation (CID) mass spectrometry experiments were carried out using electrospray ionization (ESI) ion trap mass spectrometry in positive ion mode. Also the accurate masses of fragments were measured on by ESI quadrupole time-of-flight (QTOF) MS in positive ion mode. Theoretical calculations were carried out by the density functional theory (DFT) method with the 6-31G(d) basis set in the Gaussian 03 program. In the fragmentation of the protonated esomeprazole analogs, C-S bond breakage is observed, which gives rise to protonated 2-(sulfinylmethylene)pyridines and protonated benzimidazoles. DFT calculations demonstrate that the nitrogen atom of the pyridine part is the thermodynamically most favorable protonation site, and the C-S bond cleavage is triggered by the transfer of this ionizing proton from the nitrogen atom of the pyridine part to the carbon atom of the benzimidazole part to which the sulfinyl is attached. Moreover, with the kinetic plot, the intensity ratios of two protonated product ions yield a linear relationship with the differences in proton affinities of the corresponding neutral molecules, which provides strong experimental evidence that the reaction proceeds via proton-bound 2-(sulfinylmethylene)pyridine/benzimidazole complex intermediates. The kinetic method combined with theoretical calculations was successfully applied to probe the proton transfer reaction by proton-bound 2-(sulfinylmethylene)pyridine/benzimidazole complexes in the fragmentation of protonated esomeprazole analogs by ESI CID MS, which is a strong evidence that the kinetic method can be applied in identifying a proton-bound dimeric intermediate in the fragmentation of protonated ions. Copyright © 2014 John Wiley & Sons, Ltd.

"Radiobiology of Proton Therapy": Results of an international expert workshop.

PubMed

Lühr, Armin; von Neubeck, Cläre; Pawelke, Jörg; Seidlitz, Annekatrin; Peitzsch, Claudia; Bentzen, Søren M; Bortfeld, Thomas; Debus, Jürgen; Deutsch, Eric; Langendijk, Johannes A; Loeffler, Jay S; Mohan, Radhe; Scholz, Michael; Sørensen, Brita S; Weber, Damien C; Baumann, Michael; Krause, Mechthild

2018-05-31

The physical properties of proton beams offer the potential to reduce toxicity in tumor-adjacent normal tissues. Toward this end, the number of proton radiotherapy facilities has steeply increased over the last 10-15 years to currently around 70 operational centers worldwide. However, taking full advantage of the opportunities offered by proton radiation for clinical radiotherapy requires a better understanding of the radiobiological effects of protons alone or combined with drugs or immunotherapy on normal tissues and tumors. This report summarizes the main results of the international expert workshop "Radiobiology of Proton Therapy" that was held in November 2016 in Dresden. It addresses the major topics (1) relative biological effectiveness (RBE) in proton beam therapy, (2) interaction of proton radiobiology with radiation physics in current treatment planning, (3) biological effects in proton therapy combined with systemic treatments, and (4) testing biological effects of protons in clinical trials. Finally, important research avenues for improvement of proton radiotherapy based on radiobiological knowledge are identified. The clinical distribution of radiobiological effectiveness of protons alone or in combination with systemic chemo- or immunotherapies as well as patient stratification based on biomarker expressions are key to reach the full potential of proton beam therapy. Dedicated preclinical experiments, innovative clinical trial designs, and large high-quality data repositories will be most important to achieve this goal. Copyright © 2018 Elsevier B.V. All rights reserved.

Proton affinity determinations and proton-bound dimer structure indications in C2 to C15, (alpha),(omega)-alkyldiamines

NASA Technical Reports Server (NTRS)

Karpas, Z.; Harden, C. S.; Smith, P. B. W.

1995-01-01

The 'kinetic method' was used to determine the proton affinity (PA) of a,coalkyldiamines from collision induced dissociation (CID) studies of protonated heterodimers. These PA values were consistently lower than those reported in the proton affinity scale. The apparent discrepancy was rationalized in terms of differences in the conformation of the protonated diamine monomers. The minimum energy species, formed by equilibrium proton transfer processes, have a cyclic conformation and the ion charge is shared by both amino-groups which are bridged by the proton. On the other hand, the species formed through dissociation of protonated dimers have a linear structure and the charge is localized on one of the amino-groups. Thus, the difference in the PA values obtained by both methods is a measure of the additional stability acquired by the protonated diamines through cyclization and charge delocalization. The major collision dissociation pathway of the protonated diamine monomers involved elimination of an ammonia moiety. Other reactions observed included loss of the second amino-group and several other bond cleavages. CID of the protonated dimers involved primarily formation of a protonated monomer through cleavage of the weaker hydrogen bond and subsequently loss of ammonia at higher collision energies. As observed from the CID studies, doubly charged ions were also formed from the diamines under conditions of the electrospray ionization.

Proton-driven amide bond-cleavage pathways of gas-phase peptide ions lacking mobile protons.

PubMed

Bythell, Benjamin J; Suhai, Sándor; Somogyi, Arpád; Paizs, Béla

2009-10-07

The mobile proton model (Dongre, A. R., Jones, J. L., Somogyi, A. and Wysocki, V. H. J. Am. Chem. Soc. 1996, 118 , 8365-8374) of peptide fragmentation states that the ionizing protons play a critical role in the gas-phase fragmentation of protonated peptides upon collision-induced dissociation (CID). The model distinguishes two classes of peptide ions, those with or without easily mobilizable protons. For the former class mild excitation leads to proton transfer reactions which populate amide nitrogen protonation sites. This enables facile amide bond cleavage and thus the formation of b and y sequence ions. In contrast, the latter class of peptide ions contains strongly basic functionalities which sequester the ionizing protons, thereby often hindering formation of sequence ions. Here we describe the proton-driven amide bond cleavages necessary to produce b and y ions from peptide ions lacking easily mobilizable protons. We show that this important class of peptide ions fragments by different means from those with easily mobilizable protons. We present three new amide bond cleavage mechanisms which involve salt-bridge, anhydride, and imine enol intermediates, respectively. All three new mechanisms are less energetically demanding than the classical oxazolone b(n)-y(m) pathway. These mechanisms offer an explanation for the formation of b and y ions from peptide ions with sequestered ionizing protons which are routinely fragmented in large-scale proteomics experiments.

Properties of Localized Protons in Neutron Star Matter at Finite Temperatures

NASA Astrophysics Data System (ADS)

Szmaglinski, A.; Kubis, S.; Wójcik, W.

2014-02-01

We study properties of the proton component of neutron star matter for realistic nuclear models. Vanishing of the nuclear symmetry energy implies proton-neutron separation in dense nuclear matter. Protons which form admixture tend to be localized in potential wells. Here, we extend the description of proton localization to finite temperatures. It appears that the protons are still localized at temperatures typical for hot neutron stars. That fact has important astrophysical consequences. Moreover, the temperature inclusion leads to unexpected results for the behavior of the proton localized state.

The physics of proton therapy.

PubMed

Newhauser, Wayne D; Zhang, Rui

2015-04-21

The physics of proton therapy has advanced considerably since it was proposed in 1946. Today analytical equations and numerical simulation methods are available to predict and characterize many aspects of proton therapy. This article reviews the basic aspects of the physics of proton therapy, including proton interaction mechanisms, proton transport calculations, the determination of dose from therapeutic and stray radiations, and shielding design. The article discusses underlying processes as well as selected practical experimental and theoretical methods. We conclude by briefly speculating on possible future areas of research of relevance to the physics of proton therapy.

The physics of proton therapy

PubMed Central

Newhauser, Wayne D; Zhang, Rui

2015-01-01

The physics of proton therapy has advanced considerably since it was proposed in 1946. Today analytical equations and numerical simulation methods are available to predict and characterize many aspects of proton therapy. This article reviews the basic aspects of the physics of proton therapy, including proton interaction mechanisms, proton transport calculations, the determination of dose from therapeutic and stray radiations, and shielding design. The article discusses underlying processes as well as selected practical experimental and theoretical methods. We conclude by briefly speculating on possible future areas of research of relevance to the physics of proton therapy. PMID:25803097

Theoretical investigation of local proton conductance in the proton exchange membranes

NASA Astrophysics Data System (ADS)

Singh, Raman K.; Tsuneda, Takao; Miyatake, Kenji; Watanabe, Masahiro

2014-07-01

The hydrated structures of the proton exchange membranes were theoretically investigated using long-range corrected density functional theory to make clear why perfluorinated polymer membrane Nafion is superior to other membranes in the proton conductivity at low humidity. For exploring the possibility of the proton conductance in the vehicle mechanism with low hydration numbers, we examined the relay model of protonated water clusters between the sulfonic acid groups in Nafion and concluded that this relay model may contribute to the high proton conductivity of Nafion with less-hydrated sulfonic acid groups.

A Generalized Weizsacker-Williams Method Applied to Pion Production in Proton-Proton Collisions

NASA Technical Reports Server (NTRS)

Ahern, Sean C.; Poyser, William J.; Norbury, John W.; Tripathi, R. K.

2002-01-01

A new "Generalized" Weizsacker-Williams method (GWWM) is used to calculate approximate cross sections for relativistic peripheral proton-proton collisions. Instead of a mass less photon mediator, the method allows for the mediator to have mass for short range interactions. This method generalizes the Weizsacker-Williams method (WWM) from Coulomb interactions to GWWM for strong interactions. An elastic proton-proton cross section is calculated using GWWM with experimental data for the elastic p+p interaction, where the mass p+ is now the mediator. The resulting calculated cross sections is compared to existing data for the elastic proton-proton interaction. A good approximate fit is found between the data and the calculation.

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.

Three-dimensional protonic conductivity in porous organic cage solids.

PubMed

Liu, Ming; Chen, Linjiang; Lewis, Scott; Chong, Samantha Y; Little, Marc A; Hasell, Tom; Aldous, Iain M; Brown, Craig M; Smith, Martin W; Morrison, Carole A; Hardwick, Laurence J; Cooper, Andrew I

2016-09-13

Proton conduction is a fundamental process in biology and in devices such as proton exchange membrane fuel cells. To maximize proton conduction, three-dimensional conduction pathways are preferred over one-dimensional pathways, which prevent conduction in two dimensions. Many crystalline porous solids to date show one-dimensional proton conduction. Here we report porous molecular cages with proton conductivities (up to 10(-3) S cm(-1) at high relative humidity) that compete with extended metal-organic frameworks. The structure of the organic cage imposes a conduction pathway that is necessarily three-dimensional. The cage molecules also promote proton transfer by confining the water molecules while being sufficiently flexible to allow hydrogen bond reorganization. The proton conduction is explained at the molecular level through a combination of proton conductivity measurements, crystallography, molecular simulations and quasi-elastic neutron scattering. These results provide a starting point for high-temperature, anhydrous proton conductors through inclusion of guests other than water in the cage pores.

Three-dimensional protonic conductivity in porous organic cage solids

NASA Astrophysics Data System (ADS)

Liu, Ming; Chen, Linjiang; Lewis, Scott; Chong, Samantha Y.; Little, Marc A.; Hasell, Tom; Aldous, Iain M.; Brown, Craig M.; Smith, Martin W.; Morrison, Carole A.; Hardwick, Laurence J.; Cooper, Andrew I.

2016-09-01

Proton conduction is a fundamental process in biology and in devices such as proton exchange membrane fuel cells. To maximize proton conduction, three-dimensional conduction pathways are preferred over one-dimensional pathways, which prevent conduction in two dimensions. Many crystalline porous solids to date show one-dimensional proton conduction. Here we report porous molecular cages with proton conductivities (up to 10-3 S cm-1 at high relative humidity) that compete with extended metal-organic frameworks. The structure of the organic cage imposes a conduction pathway that is necessarily three-dimensional. The cage molecules also promote proton transfer by confining the water molecules while being sufficiently flexible to allow hydrogen bond reorganization. The proton conduction is explained at the molecular level through a combination of proton conductivity measurements, crystallography, molecular simulations and quasi-elastic neutron scattering. These results provide a starting point for high-temperature, anhydrous proton conductors through inclusion of guests other than water in the cage pores.

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

Proton energy and scattering angle radiographs to improve proton treatment planning: a Monte Carlo study

NASA Astrophysics Data System (ADS)

Biegun, A. K.; Takatsu, J.; Nakaji, T.; van Goethem, M. J.; van der Graaf, E. R.; Koffeman, E. N.; Visser, J.; Brandenburg, S.

2016-12-01

The novel proton radiography imaging technique has a large potential to be used in direct measurement of the proton energy loss (proton stopping power, PSP) in various tissues in the patient. The uncertainty of PSPs, currently obtained from translation of X-ray Computed Tomography (xCT) images, should be minimized from 3-5% or higher to less than 1%, to make the treatment plan with proton beams more accurate, and thereby better treatment for the patient. With Geant4 we simulated a proton radiography detection system with two position-sensitive and residual energy detectors. A complex phantom filled with various materials (including tissue surrogates), was placed between the position sensitive detectors. The phantom was irradiated with 150 MeV protons and the energy loss radiograph and scattering angles were studied. Protons passing through different materials in the phantom lose energy, which was used to create a radiography image of the phantom. The multiple Coulomb scattering of a proton traversing different materials causes blurring of the image. To improve image quality and material identification in the phantom, we selected protons with small scattering angles. A good quality proton radiography image, in which various materials can be recognized accurately, and in combination with xCT can lead to more accurate relative stopping powers predictions.

Density Functional Theory Investigation of Proton Diffusion in Tungsten Oxide And Its Hydrates

NASA Astrophysics Data System (ADS)

Lin, Hao

Fast proton conduction mechanism is of key importance for achieving high performance in fuel cell membranes, batteries, supercapacitors, and electrochromic materials. Enhanced proton diffusion is often observed in hydrated materials where it is thought to occur via the famous Grotthuss mechanism through pathways formed by structural water. Using first-principles calculations, we demonstrate that proton diffusion in tungsten oxide dihydrate (WO3·2H 2O), a known good proton conductor, takes place within the layers of corner-sharing WO6 octahedra without direct involvement of structural water. The calculated proton migration barrier in WO3·2H 2O is in good agreement with the experimental value inferred from the temperature dependence of conductivity. The preferred proton diffusion path in WO3·2H2O is essentially the same as in gamma-WO 3. In contrast to the small intercalation voltages calculated for WO 3 and WO3·2H2O, we find that proton absorption in the monohydrate WO3·H2O is energetically highly favorable. However, strong proton-proton repulsion limits the equilibrium H content at zero voltage. We find a fast one-dimensional diffusion channel in WO3·H2O at dilute proton concentrations, but much higher barriers are expected at near-equilibrium concentrations due to strong repulsive interactions with other protons. Our results illustrate that low proton diffusion barriers and low insertion voltages both contribute to fast proton transport in bulk WO3·2H2O and gamma-WO 3.

The optimal balance between quality and efficiency in proton radiography imaging technique at various proton beam energies: A Monte Carlo study.

PubMed

Biegun, A K; van Goethem, M-J; van der Graaf, E R; van Beuzekom, M; Koffeman, E N; Nakaji, T; Takatsu, J; Visser, J; Brandenburg, S

2017-09-01

Proton radiography is a novel imaging modality that allows direct measurement of the proton energy loss in various tissues. Currently, due to the conversion of so-called Hounsfield units from X-ray Computed Tomography (CT) into relative proton stopping powers (RPSP), the uncertainties of RPSP are 3-5% or higher, which need to be minimized down to 1% to make the proton treatment plans more accurate. In this work, we simulated a proton radiography system, with position-sensitive detectors (PSDs) and a residual energy detector (RED). The simulations were built using Geant4, a Monte Carlo simulation toolkit. A phantom, consisting of several materials was placed between the PSDs of various Water Equivalent Thicknesses (WET), corresponding to an ideal detector, a gaseous detector, silicon and plastic scintillator detectors. The energy loss radiograph and the scattering angle distributions of the protons were studied for proton beam energies of 150MeV, 190MeV and 230MeV. To improve the image quality deteriorated by the multiple Coulomb scattering (MCS), protons with small angles were selected. Two ways of calculating a scattering angle were considered using the proton's direction and position. A scattering angle cut of 8.7mrad was applied giving an optimal balance between quality and efficiency of the radiographic image. For the three proton beam energies, the number of protons used in image reconstruction with the direction method was half the number of protons kept using the position method. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

How proton pulse characteristics influence protoacoustic determination of proton-beam range: simulation studies.

PubMed

Jones, Kevin C; Seghal, Chandra M; Avery, Stephen

2016-03-21

The unique dose deposition of proton beams generates a distinctive thermoacoustic (protoacoustic) signal, which can be used to calculate the proton range. To identify the expected protoacoustic amplitude, frequency, and arrival time for different proton pulse characteristics encountered at hospital-based proton sources, the protoacoustic pressure emissions generated by 150 MeV, pencil-beam proton pulses were simulated in a homogeneous water medium. Proton pulses with Gaussian widths ranging up to 200 μs were considered. The protoacoustic amplitude, frequency, and time-of-flight (TOF) range accuracy were assessed. For TOF calculations, the acoustic pulse arrival time was determined based on multiple features of the wave. Based on the simulations, Gaussian proton pulses can be categorized as Dirac-delta-function-like (FWHM < 4 μs) and longer. For the δ-function-like irradiation, the protoacoustic spectrum peaks at 44.5 kHz and the systematic error in determining the Bragg peak range is <2.6 mm. For longer proton pulses, the spectrum shifts to lower frequencies, and the range calculation systematic error increases (⩽ 23 mm for FWHM of 56 μs). By mapping the protoacoustic peak arrival time to range with simulations, the residual error can be reduced. Using a proton pulse with FWHM = 2 μs results in a maximum signal-to-noise ratio per total dose. Simulations predict that a 300 nA, 150 MeV, FWHM = 4 μs Gaussian proton pulse (8.0 × 10(6) protons, 3.1 cGy dose at the Bragg peak) will generate a 146 mPa pressure wave at 5 cm beyond the Bragg peak. There is an angle dependent systematic error in the protoacoustic TOF range calculations. Placing detectors along the proton beam axis and beyond the Bragg peak minimizes this error. For clinical proton beams, protoacoustic detectors should be sensitive to <400 kHz (for -20 dB). Hospital-based synchrocyclotrons and cyclotrons are promising sources of proton pulses for generating clinically measurable protoacoustic emissions.

Maximum proton kinetic energy and patient-generated neutron fluence considerations in proton beam arc delivery radiation therapy.

PubMed

Sengbusch, E; Pérez-Andújar, A; DeLuca, P M; Mackie, T R

2009-02-01

Several compact proton accelerator systems for use in proton therapy have recently been proposed. Of paramount importance to the development of such an accelerator system is the maximum kinetic energy of protons, immediately prior to entry into the patient, that must be reached by the treatment system. The commonly used value for the maximum kinetic energy required for a medical proton accelerator is 250 MeV, but it has not been demonstrated that this energy is indeed necessary to treat all or most patients eligible for proton therapy. This article quantifies the maximum kinetic energy of protons, immediately prior to entry into the patient, necessary to treat a given percentage of patients with rotational proton therapy, and examines the impact of this energy threshold on the cost and feasibility of a compact, gantry-mounted proton accelerator treatment system. One hundred randomized treatment plans from patients treated with IMRT were analyzed. The maximum radiological pathlength from the surface of the patient to the distal edge of the treatment volume was obtained for 180 degrees continuous arc proton therapy and for 180 degrees split arc proton therapy (two 90 degrees arcs) using CT# profiles from the Pinnacle (Philips Medical Systems, Madison, WI) treatment planning system. In each case, the maximum kinetic energy of protons, immediately prior to entry into the patient, that would be necessary to treat the patient was calculated using proton range tables for various media. In addition, Monte Carlo simulations were performed to quantify neutron production in a water phantom representing a patient as a function of the maximum proton kinetic energy achievable by a proton treatment system. Protons with a kinetic energy of 240 MeV, immediately prior to entry into the patient, were needed to treat 100% of patients in this study. However, it was shown that 90% of patients could be treated at 198 MeV, and 95% of patients could be treated at 207 MeV. Decreasing the proton kinetic energy from 250 to 200 MeV decreases the total neutron energy fluence produced by stopping a monoenergetic pencil beam in a water phantom by a factor of 2.3. It is possible to significantly lower the requirements on the maximum kinetic energy of a compact proton accelerator if the ability to treat a small percentage of patients with rotational therapy is sacrificed. This decrease in maximum kinetic energy, along with the corresponding decrease in neutron production, could lower the cost and ease the engineering constraints on a compact proton accelerator treatment facility.

Proton-Proton and Proton-Antiproton Colliders

NASA Astrophysics Data System (ADS)

Scandale, Walter

In the last five decades, proton-proton and proton-antiproton colliders have been the most powerful tools for high energy physics investigations. They have also deeply catalyzed innovation in accelerator physics and technology. Among the large number of proposed colliders, only four have really succeeded in becoming operational: the ISR, the SppbarS, the Tevatron and the LHC. Another hadron collider, RHIC, originally conceived for ion-ion collisions, has also been operated part-time with polarized protons. Although a vast literature documenting them is available, this paper is intended to provide a quick synthesis of their main features and key performance.

Proton-Proton and Proton-Antiproton Colliders

NASA Astrophysics Data System (ADS)

Scandale, Walter

2014-04-01

In the last five decades, proton-proton and proton-antiproton colliders have been the most powerful tools for high energy physics investigations. They have also deeply catalyzed innovation in accelerator physics and technology. Among the large number of proposed colliders, only four have really succeeded in becoming operational: the ISR, the SppbarS, the Tevatron and the LHC. Another hadron collider, RHIC, originally conceived for ion-ion collisions, has also been operated part-time with polarized protons. Although a vast literature documenting them is available, this paper is intended to provide a quick synthesis of their main features and key performance.

Proton-Proton and Proton-Antiproton Colliders

NASA Astrophysics Data System (ADS)

Scandale, Walter

2015-02-01

In the last five decades, proton-proton and proton-antiproton colliders have been the most powerful tools for high energy physics investigations. They have also deeply catalyzed innovation in accelerator physics and technology. Among the large number of proposed colliders, only four have really succeeded in becoming operational: the ISR, the SppbarS, the Tevatron and the LHC. Another hadron collider, RHIC, originally conceived for ion-ion collisions, has also been operated part-time with polarized protons. Although a vast literature documenting them is available, this paper is intended to provide a quick synthesis of their main features and key performance.

Magnetic quadrupoles lens for hot spot proton imaging in inertial confinement fusion

NASA Astrophysics Data System (ADS)

Teng, J.; Gu, Y. Q.; Chen, J.; Zhu, B.; Zhang, B.; Zhang, T. K.; Tan, F.; Hong, W.; Zhang, B. H.; Wang, X. Q.

2016-08-01

Imaging of DD-produced protons from an implosion hot spot region by miniature permanent magnetic quadrupole (PMQ) lens is proposed. Corresponding object-image relation is deduced and an adjust method for this imaging system is discussed. Ideal point-to-point imaging demands a monoenergetic proton source; nevertheless, we proved that the blur of image induced by proton energy spread is a second order effect therefore controllable. A proton imaging system based on miniature PMQ lens is designed for 2.8 MeV DD-protons and the adjust method in case of proton energy shift is proposed. The spatial resolution of this system is better than 10 μm when proton yield is above 109 and the spectra width is within 10%.

Measurements of Reaction Cross Sections for 9-11C

NASA Astrophysics Data System (ADS)

Nishizuka, Kenji; Takechi, Maya; Ohtsubo, Takashi; Nishimura, Daiki; Fukuda, Mitsunori; Aoki, Kazuya; Abe, Keijiro; Ikeda, Ayaka; Izumikawa, Takuji; Oikawa, Hiroyuki; Ohnishi, Kosuke; Ohno, Junichi; Ohmika, Shunichiro; Kato, Ikuma; Kanke, Yuki; Kanbe, Shunsuke; Kanda, Naoto; Kikuchi, Haruka; Kitagawa, Atsushi; Sato, Shinji; Sayama, Umito; Shimaya, Jiro; Sugihara, Takanobu; Suzuki, Shinji; Suzuki, Takeshi; Takahashi, Hiroki; Taguchi, Yoshisada; Takei, Yuki; Takeuchi, Yuki; Takenouchi, Arashi; Takemoto, Takanori; Tadano, Natsuki; Tanaka, Masaomi; Tanaka, Yutaro; Chikaato, Kazuya; Du, Hang; Nagai, Takumi; Nagumo, Junya; Fukuda, Shigekazu; Hori, Kensyu; Honma, Akira; Machida, Masahiro; Matsunaga, Satoshi; Mizukami, Atsushi; Mihara, Mototsugu; Miyata, Eri; Murooka, Daiki; Yagi, Shoichi; Yamaoka, Shintaro; Yamaguchi, Takayuki; Yokoyama, Kouhei

In order to probe the differences of matter and charge radii of atomic nucleus in the proton-rich C isotopes, measurements of reaction cross sections (σR) for 9-11C on proton targets in the energy range from 50 to 120A MeV were performed at HIMAC facility, NIRS. Owing to the large differences between proton-proton and proton-neutron scattering cross sections at this intermediate energy region, σR data for atomic nuclei on proton targets are expected to have the sensitivity to the differences between proton and neutron distributions in the nucleus. Present preliminary data are compared with the Glauber calculation, which suggest the larger enhancements of proton distributions in 9C and 10C compared to 11C.

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

Energetic Proton Spectra Measured by the Van Allen Probes

NASA Astrophysics Data System (ADS)

Summers, Danny; Shi, Run; Engebretson, Mark J.; Oksavik, Kjellmar; Manweiler, Jerry W.; Mitchell, Donald G.

2017-10-01

We test the hypothesis that pitch angle scattering by electromagnetic ion cyclotron (EMIC) waves can limit ring current proton fluxes. For two chosen magnetic storms, during 17-20 March 2013 and 17-20 March 2015, we measure proton energy spectra in the region 3 ≤ L ≤ 6 using the RBSPICE-B instrument on the Van Allen Probes. The most intense proton spectra are observed to occur during the recovery periods of the respective storms. Using proton precipitation data from the POES (NOAA and MetOp) spacecraft, we deduce that EMIC wave action was prevalent at the times and L-shell locations of the most intense proton spectra. We calculate limiting ring current proton energy spectra from recently developed theory. Comparisons between the observed proton energy spectra and the theoretical limiting spectra show reasonable agreement. We conclude that the measurements of the most intense proton spectra are consistent with self-limiting by EMIC wave scattering.

An analytical reconstruction model of the spread-out Bragg peak using laser-accelerated proton beams.

PubMed

Tao, Li; Zhu, Kun; Zhu, Jungao; Xu, Xiaohan; Lin, Chen; Ma, Wenjun; Lu, Haiyang; Zhao, Yanying; Lu, Yuanrong; Chen, Jia-Er; Yan, Xueqing

2017-07-07

With the development of laser technology, laser-driven proton acceleration provides a new method for proton tumor therapy. However, it has not been applied in practice because of the wide and decreasing energy spectrum of laser-accelerated proton beams. In this paper, we propose an analytical model to reconstruct the spread-out Bragg peak (SOBP) using laser-accelerated proton beams. Firstly, we present a modified weighting formula for protons of different energies. Secondly, a theoretical model for the reconstruction of SOBPs with laser-accelerated proton beams has been built. It can quickly calculate the number of laser shots needed for each energy interval of the laser-accelerated protons. Finally, we show the 2D reconstruction results of SOBPs for laser-accelerated proton beams and the ideal situation. The final results show that our analytical model can give an SOBP reconstruction scheme that can be used for actual tumor therapy.

The mechanism of proton conduction in phosphoric acid

NASA Astrophysics Data System (ADS)

Vilčiauskas, Linas; Tuckerman, Mark E.; Bester, Gabriel; Paddison, Stephen J.; Kreuer, Klaus-Dieter

2012-06-01

Neat liquid phosphoric acid (H3PO4) has the highest intrinsic proton conductivity of any known substance and is a useful model for understanding proton transport in other phosphate-based systems in biology and clean energy technologies. Here, we present an ab initio molecular dynamics study that reveals, for the first time, the microscopic mechanism of this high proton conductivity. Anomalously fast proton transport in hydrogen-bonded systems involves a structural diffusion mechanism in which intramolecular proton transfer is driven by specific hydrogen bond rearrangements in the surrounding environment. Aqueous media transport excess charge defects through local hydrogen bond rearrangements that drive individual proton transfer reactions. In contrast, strong, polarizable hydrogen bonds in phosphoric acid produce coupled proton motion and a pronounced protic dielectric response of the medium, leading to the formation of extended, polarized hydrogen-bonded chains. The interplay between these chains and a frustrated hydrogen-bond network gives rise to the high proton conductivity.

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

Proton therapy in clinical practice

PubMed Central

Liu, Hui; Chang, Joe Y.

2011-01-01

Radiation dose escalation and acceleration improves local control but also increases toxicity. Proton radiation is an emerging therapy for localized cancers that is being sought with increasing frequency by patients. Compared with photon therapy, proton therapy spares more critical structures due to its unique physics. The physical properties of a proton beam make it ideal for clinical applications. By modulating the Bragg peak of protons in energy and time, a conformal radiation dose with or without intensity modulation can be delivered to the target while sparing the surrounding normal tissues. Thus, proton therapy is ideal when organ preservation is a priority. However, protons are more sensitive to organ motion and anatomy changes compared with photons. In this article, we review practical issues of proton therapy, describe its image-guided treatment planning and delivery, discuss clinical outcome for cancer patients, and suggest challenges and the future development of proton therapy. PMID:21527064

The Protonation Site of para-Dimethylaminobenzoic Acid Using Atmospheric Pressure Ionization Methods

NASA Astrophysics Data System (ADS)

Chai, Yunfeng; Weng, Guofeng; Shen, Shanshan; Sun, Cuirong; Pan, Yuanjiang

2015-04-01

The protonation site of para-dimethylaminobenzoic acid ( p-DMABA) was investigated using atmospheric pressure ionization methods (ESI and APCI) coupled with collision-induced dissociation (CID), nuclear magnetic resonance (NMR), and computational chemistry. Theoretical calculations and NMR experiments indicate that the dimethyl amino group is the preferred site of protonation both in the gas phase and aqueous solution. Protonation of p-DMABA occurs at the nitrogen atom by ESI independent of the solvents and other operation conditions under typical thermodynamic control. However, APCI produces a mixture of the nitrogen- and carbonyl oxygen-protonated p-DMABA when aprotic organic solvents (acetonitrile, acetone, and tetrahydrofuran) are used, exhibiting evident kinetic characteristics of protonation. But using protic organic solvents (methanol, ethanol, and isopropanol) in APCI still leads to the formation of thermodynamically stable N-protonated p-DMABA. These structural assignments were based on the different CID behavior of the N- and O-protonated p-DMABA. The losses of methyl radical and water are the diagnostic fragmentations of the N- and O-protonated p-DMABA, respectively. In addition, the N-protonated p-DMABA is more stable than the O-protonated p-DMABA in CID revealed by energy resolved experiments and theoretical calculations.

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.

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.

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.

Three-Dimensional Magnetohydrodynamic Modeling of the Solar Wind Including Pickup Protons and Turbulence Transport

NASA Technical Reports Server (NTRS)

Usmanov, Arcadi V.; Goldstein, Melvyn L.; Matthaeus, William H.

2012-01-01

To study the effects of interstellar pickup protons and turbulence on the structure and dynamics of the solar wind, we have developed a fully three-dimensional magnetohydrodynamic solar wind model that treats interstellar pickup protons as a separate fluid and incorporates the transport of turbulence and turbulent heating. The governing system of equations combines the mean-field equations for the solar wind plasma, magnetic field, and pickup protons and the turbulence transport equations for the turbulent energy, normalized cross-helicity, and correlation length. The model equations account for photoionization of interstellar hydrogen atoms and their charge exchange with solar wind protons, energy transfer from pickup protons to solar wind protons, and plasma heating by turbulent dissipation. Separate mass and energy equations are used for the solar wind and pickup protons, though a single momentum equation is employed under the assumption that the pickup protons are comoving with the solar wind protons.We compute the global structure of the solar wind plasma, magnetic field, and turbulence in the region from 0.3 to 100 AU for a source magnetic dipole on the Sun tilted by 0 deg - .90 deg and compare our results with Voyager 2 observations. The results computed with and without pickup protons are superposed to evaluate quantitatively the deceleration and heating effects of pickup protons, the overall compression of the magnetic field in the outer heliosphere caused by deceleration, and the weakening of corotating interaction regions by the thermal pressure of pickup protons.

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.

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.

Moving protons with pendant amines: proton mobility in a nickel catalyst for oxidation of hydrogen.

PubMed

O'Hagan, Molly; Shaw, Wendy J; Raugei, Simone; Chen, Shentan; Yang, Jenny Y; Kilgore, Uriah J; DuBois, Daniel L; Bullock, R Morris

2011-09-14

Proton transport is ubiquitous in chemical and biological processes, including the reduction of dioxygen to water, the reduction of CO(2) to formate, and the production/oxidation of hydrogen. In this work we describe intramolecular proton transfer between Ni and positioned pendant amines for the hydrogen oxidation electrocatalyst [Ni(P(Cy)(2)N(Bn)(2)H)(2)](2+) (P(Cy)(2)N(Bn)(2) = 1,5-dibenzyl-3,7-dicyclohexyl-1,5-diaza-3,7-diphosphacyclooctane). Rate constants are determined by variable-temperature one-dimensional NMR techniques and two-dimensional EXSY experiments. Computational studies provide insight into the details of the proton movement and energetics of these complexes. Intramolecular proton exchange processes are observed for two of the three experimentally observable isomers of the doubly protonated Ni(0) complex, [Ni(P(Cy)(2)N(Bn)(2)H)(2)](2+), which have N-H bonds but no Ni-H bonds. For these two isomers, with pendant amines positioned endo to the Ni, the rate constants for proton exchange range from 10(4) to 10(5) s(-1) at 25 °C, depending on isomer and solvent. No exchange is observed for protons on pendant amines positioned exo to the Ni. Analysis of the exchange as a function of temperature provides a barrier for proton exchange of ΔG(‡) = 11-12 kcal/mol for both isomers, with little dependence on solvent. Density functional theory calculations and molecular dynamics simulations support the experimental observations, suggesting metal-mediated intramolecular proton transfers between nitrogen atoms, with chair-to-boat isomerizations as the rate-limiting steps. Because of the fast rate of proton movement, this catalyst may be considered a metal center surrounded by a cloud of exchanging protons. The high intramolecular proton mobility provides information directly pertinent to the ability of pendant amines to accelerate proton transfers during catalysis of hydrogen oxidation. These results may also have broader implications for proton movement in homogeneous catalysts and enzymes in general, with specific implications for the proton channel in the Ni-Fe hydrogenase enzyme.

An experimental demonstration of a new type of proton computed tomography using a novel silicon tracking detector.

PubMed

Taylor, J T; Poludniowski, G; Price, T; Waltham, C; Allport, P P; Casse, G L; Esposito, M; Evans, P M; Green, S; Manger, S; Manolopoulos, S; Nieto-Camero, J; Parker, D J; Symons, J; Allinson, N M

2016-11-01

Radiography and tomography using proton beams promise benefit to image guidance and treatment planning for proton therapy. A novel proton tracking detector is described and experimental demonstrations at a therapy facility are reported. A new type of proton CT reconstructing relative "scattering power" rather than "stopping power" is also demonstrated. Notably, this new type of imaging does not require the measurement of the residual energies of the protons. A large area, silicon microstrip tracker with high spatial and temporal resolution has been developed by the Proton Radiotherapy Verification and Dosimetry Applications consortium and commissioned using beams of protons at iThemba LABS, Medical Radiation Department, South Africa. The tracker comprises twelve planes of silicon developed using technology from high energy physics with each plane having an active area of ∼10 × 10 cm segmented into 2048 microstrips. The tracker is organized into four separate units each containing three detectors at 60° to one another creating an x-u-v coordinate system. Pairs of tracking units are used to reconstruct vertices for protons entering and exiting a phantom containing tissue equivalent inserts. By measuring the position and direction of each proton before and after the phantom, the nonlinear path for each proton through an object can be reconstructed. Experimental results are reported for tracking the path of protons with initial energies of 125 and 191 MeV. A spherical phantom of 75 mm diameter was imaged by positioning it between the entrance and exit detectors of the tracker. Positions and directions of individual protons were used to create angular distributions and 2D fluence maps of the beam. These results were acquired for 36 equally spaced projections spanning 180°, allowing, for the first time, an experimental CT image based upon the relative scattering power of protons to be reconstructed. Successful tracking of protons through a thick target (phantom) has demonstrated that the tracker discussed in this paper can provide the precise directional information needed to perform proton radiography and tomography. When synchronized with a range telescope, this could enable the reconstruction of proton CT images of stopping power. Furthermore, by measuring the deflection of many protons through a phantom, it was demonstrated that it is possible to reconstruct a new kind of CT image (scattering power) based upon this tracking information alone.

Proton tracking in a high-granularity Digital Tracking Calorimeter for proton CT purposes

NASA Astrophysics Data System (ADS)

Pettersen, H. E. S.; Alme, J.; Biegun, A.; van den Brink, A.; Chaar, M.; Fehlker, D.; Meric, I.; Odland, O. H.; Peitzmann, T.; Rocco, E.; Ullaland, K.; Wang, H.; Yang, S.; Zhang, C.; Röhrich, D.

2017-07-01

Radiation therapy with protons as of today utilizes information from x-ray CT in order to estimate the proton stopping power of the traversed tissue in a patient. The conversion from x-ray attenuation to proton stopping power in tissue introduces range uncertainties of the order of 2-3% of the range, uncertainties that are contributing to an increase of the necessary planning margins added to the target volume in a patient. Imaging methods and modalities, such as Dual Energy CT and proton CT, have come into consideration in the pursuit of obtaining an as good as possible estimate of the proton stopping power. In this study, a Digital Tracking Calorimeter is benchmarked for proof-of-concept for proton CT purposes. The Digital Tracking Calorimeter was originally designed for the reconstruction of high-energy electromagnetic showers for the ALICE-FoCal project. The presented prototype forms the basis for a proton CT system using a single technology for tracking and calorimetry. This advantage simplifies the setup and reduces the cost of a proton CT system assembly, and it is a unique feature of the Digital Tracking Calorimeter concept. Data from the AGORFIRM beamline at KVI-CART in Groningen in the Netherlands and Monte Carlo simulation results are used to in order to develop a tracking algorithm for the estimation of the residual ranges of a high number of concurrent proton tracks. High energy protons traversing the detector leave a track through the sensor layers. These tracks are spread out through charge diffusion processes. A charge diffusion model is applied for acquisition of estimates of the deposited energy of the protons in each sensor layer by using the size of the charge diffused area. A model fit of the Bragg Curve is applied to each reconstructed track and through this, estimating the residual range of each proton. The range of the individual protons can at present be estimated with a resolution of 4%. The readout system for this prototype is able to handle an effective proton frequency of 1 MHz by using 500 concurrent proton tracks in each readout frame, which is at the high end range of present similar prototypes. A future further optimized prototype will enable a high-speed and more accurate determination of the ranges of individual protons in a therapeutic beam.

Proton permeation of lipid bilayers.

PubMed

Deamer, D W

1987-10-01

Proton permeation of the lipid bilayer barrier has two unique features. First, permeability coefficients measured at neutral pH ranges are six to seven orders of magnitude greater than expected from knowledge of other monovalent cations. Second, proton conductance across planar lipid bilayers varies at most by a factor of 10 when pH is varied from near 1 to near 11. Two mechanisms have been proposed to account for this anomalous behavior: proton conductance related to contaminants of lipid bilayers, and proton translocation along transient hydrogen-bonded chains (tHBC) of associated water molecules in the membrane. The weight of evidence suggests that trace contaminants may contribute to proton conductance across planar lipid membranes at certain pH ranges, but cannot account for the anomalous proton flux in liposome systems. Two new results will be reported here which were designed to test the tHBC model. These include measurements of relative proton/potassium permeability in the gramicidin channel, and plots of proton flux against the magnitude of pH gradients. (1) The relative permeabilities of protons and potassium through the gramicidin channel, which contains a single strand of hydrogen-bonded water molecules, were found to differ by at least four orders of magnitude when measured at neutral pH ranges. This result demonstrates that a hydrogen-bonded chain of water molecules can provide substantial discrimination between protons and other cations. It was also possible to calculate that if approximately 7% of bilayer water was present in a transient configuration similar to that of the gramicidin channel, it could account for the measured proton flux. (2) The plot of proton conductance against pH gradient across liposome membranes was superlinear, a result that is consistent with one of three alternative tHBC models for proton conductance described by Nagle elsewhere in this volume.

Rectified Proton Grotthuss Conduction Across a Long Water-Wire in the Test Nanotube of the Polytheonamide B Channel.

PubMed

Matsuki, Yuka; Iwamoto, Masayuki; Mita, Kenichiro; Shigemi, Kenji; Matsunaga, Shigeki; Oiki, Shigetoshi

2016-03-30

A hydrogen-bonded water-chain in a nanotube is highly proton conductive, and examining the proton flux under electric fields is crucial to understanding the one-dimensional Grotthuss conduction. Here, we exploited a nanotube-forming natural product, the peptide polytheonamide B (pTB), to examine proton conduction mechanisms at a single-molecule level. The pTB nanotube has a length of ∼40 Å that spans the membrane and a uniform inner diameter of 4 Å that holds a single-file water-chain. Single-channel proton currents were measured using planar lipid bilayers in various proton concentrations and membrane potentials (±400 mV). We found, surprisingly, that the current-voltage curves were asymmetric with symmetric proton concentrations in both solutions across the membrane (rectification). The proton flux from the C-terminal to the N-terminal end was 1.6 times higher than that from the opposite. At lower proton concentrations, the degree of rectification was attenuated, but with the addition of a pH-buffer (dichloroacetate) that supplies protons near the entrance, the rectification emerged. These results indicate that the permeation processes inside the pore generate the rectification, which is masked at low concentrations by the diffusion-limited access of protons to the pore entrance. The permeation processes were characterized by a discrete-state Markov model, in which hops of a proton followed by water-chain turnovers were implemented. The optimized model revealed that the water-chain turnover exhibited unusual voltage dependence, and the distinct voltage-dependencies of the forward and backward transition rates yielded the rectification. The pTB nanotube serves as a rectified proton conductor, and the design principles can be exploited for proton-conducting materials.

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

PubMed

Dance, Ian

2012-07-07

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

A model for proton-irradiated GaAs solar cells

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Walker, G. H.; Outlaw, R. A.; Stock, L. V.

1982-01-01

A simple model for proton radiation damage in GaAs heteroface solar cells is developed. The model includes the effects of spatial nonuniformity of low energy proton damage. Agreement between the model and experimental proton damage data for GaAs heteroface solar cells is satisfactory. An extension of the model to include angular isotropy, as is appropriate for protons in space, is shown to result in significantly less cell damage than for normal proton incidence.

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.

Electron-proton spectrometer design summary

NASA Technical Reports Server (NTRS)

1972-01-01

The electron-proton spectrometer (EPS) will be placed aboard the Skylab in order to provide data from which electron and proton radiation dose can be determined. The EPS has five sensors, each consisting of a shielded silicon detector. These provide four integral electron channels and five integral proton channels from which can be deduced four differential proton increments.

Effect of target composition on proton acceleration in ultraintense laser-thin foil interaction

NASA Astrophysics Data System (ADS)

Liu, Qingcao; Liu, Meng; Yu, Tongpu; Ding, Pengji; Liu, Zuoye; Sun, Shaohua; Liu, Xiaoliang; Lu, Xing; Guo, Zeqin; Hu, Bitao

2012-09-01

The interactions of ultraintense circularly polarized laser pulses with a mixed solid target and a double-layer target are studied by two-dimensional particle-in-cell simulations. Different carbon and proton compositions in the targets are used in the simulations. It is shown that the proton acceleration mechanisms in both targets are very sensitive to the ion density ratios between protons and carbon ions. For a mixed solid target, a relatively low proton density gives rise to monoenergetic peaks in the proton energy spectrum while a high proton density leads to a large cut-off energy and wide energy spread. With the increase of the ratio, the so-called directed-Coulomb-explosion becomes dominated over the radiation pressure. Surprisingly, for a double-layer target with a front proton layer and an ultrathin rear carbon layer, a highly monoenergetic proton beam with a peak energy of 1.7 GeV/u, an energy spread of ˜4%, and a divergency angle of 2° can be obtained, which might have diverse applications in medical therepy and proton imaging in future.

YAP(Ce) crystal characterization with proton beam up to 60 MeV

NASA Astrophysics Data System (ADS)

Randazzo, N.; Sipala, V.; Aiello, S.; Lo Presti, D.; Cirrone, G. A. P.; Cuttone, G.; Di Rosa, F.

2008-02-01

A YAP(Ce) crystal was characterized with a proton beam up to 60 MeV. Tests were performed to investigate the possibility of using this detector as a proton calorimeter. The size of the crystal was chosen so that the proton energy is totally lost inside the medium. The authors propose to use the YAP(Ce) crystal in medical applications for proton therapy. In particular, in proton computed tomography (pCT) project it is necessary as a calorimeter in order to measure the proton residual energy after the phantom. Energy resolution, linearity, and light yield were measured in the Laboratori Nazionali del Sud with the CATANA proton beam [ http://www.lns.infn.it/CATANA/CATANA] and the results are shown in this paper. The crystal shows a good resolution (3% at 60 MeV proton beam) and it shows good linearity for different proton beam energies (1% at 30-60 MeV energy range). The crystal performances confirm that the YAP(Ce) crystal represents a good solution for these kinds of application.

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.

Molecular Dynamics Studies of Proton Transport in Hydrogenase and Hydrogenase Mimics

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

Ginovska-Pangovska, Bojana; Raugei, Simone; Shaw, Wendy J.

2016-08-02

Protons are used throughout the biological world for a number of functions, from charge balance to energy carriers. Metalloenzymes use protons as energy carriers and control proton movement both temporally and spatially. Despite the interest and need for controlled proton movement in other systems, the scientific community has not been able to develop extensive general rules for developing synthetic proton pathways. In part this is due to the challenging nature of studying these large and complex molecules experimentally, although experiments have gleaned extensive critical insight. While computational methods are also challenging because of the large size of the molecules, theymore » have been critical in advancing our knowledge of proton movement through pathways, but even further, they have advanced our knowledge in how protonation and proton movement is correlated with large and small scale molecular motions and electron movement. These studies often complement experimental studies but provide insight and depth simply not possible in many cases in the absence of theory. In this chapter, we will discuss advances and methods used in understanding proton movement in hydrogenases.« less

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

[Proton imaging applications for proton therapy: state of the art].

PubMed

Amblard, R; Floquet, V; Angellier, G; Hannoun-Lévi, J M; Hérault, J

2015-04-01

Proton therapy allows a highly precise tumour volume irradiation with a low dose delivered to the healthy tissues. The steep dose gradients observed and the high treatment conformity require a precise knowledge of the proton range in matter and the target volume position relative to the beam. Thus, proton imaging allows an improvement of the treatment accuracy, and thereby, in treatment quality. Initially suggested in 1963, radiographic imaging with proton is still not used in clinical routine. The principal difficulty is the lack of spatial resolution, induced by the multiple Coulomb scattering of protons with nuclei. Moreover, its realization for all clinical locations requires relatively high energies that are previously not considered for clinical routine. Abandoned for some time in favor of X-ray technologies, research into new imaging methods using protons is back in the news because of the increase of proton radiation therapy centers in the world. This article exhibits a non-exhaustive state of the art in proton imaging. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

FPGA-based trigger system for the Fermilab SeaQuest experimentz

NASA Astrophysics Data System (ADS)

Shiu, Shiuan-Hal; Wu, Jinyuan; McClellan, Randall Evan; Chang, Ting-Hua; Chang, Wen-Chen; Chen, Yen-Chu; Gilman, Ron; Nakano, Kenichi; Peng, Jen-Chieh; Wang, Su-Yin

2015-12-01

The SeaQuest experiment (Fermilab E906) detects pairs of energetic μ+ and μ- produced in 120 GeV/c proton-nucleon interactions in a high rate environment. The trigger system consists of several arrays of scintillator hodoscopes and a set of field-programmable gate array (FPGA) based VMEbus modules. Signals from up to 96 channels of hodoscope are digitized by each FPGA with a 1-ns resolution using the time-to-digital convertor (TDC) firmware. The delay of the TDC output can be adjusted channel-by-channel in 1-ns step and then re-aligned with the beam RF clock. The hit pattern on the hodoscope planes is then examined against pre-determined trigger matrices to identify candidate muon tracks. Information on the candidate tracks is sent to the 2nd-level FPGA-based track correlator to find candidate di-muon events. The design and implementation of the FPGA-based trigger system for SeaQuest experiment are presented.

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

DOE PAGES

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

2016-08-22

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

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

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

Nogly, Przemyslaw; Panneels, Valerie; Nelson, Garrett

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

Coupling of lithium niobate disk resonators to integrated waveguides

NASA Astrophysics Data System (ADS)

Berneschi, S.; Cosi, F.; Nunzi Conti, G.; Pelli, S.; Soria, S.; Righini, G. C.; Dispenza, M.; Secchi, A.

2011-01-01

Whispering gallery mode (WGM) disk resonators fabricated in single crystals can have high Q factors within their transparency bandwidth and may have application both in fundamental and applied optics. Lithium niobate (LN) resonators thanks to their electro-optical properties may be used in particular as tunable filters, modulators, and delay lines. A critical step toward the actual application of these devices is the implementation of a robust and efficient coupling system. High index prisms are typically used for this purpose. In this work we demonstrate coupling to high-Q WGM LN disks from an integrated optical LN waveguide. The waveguides are made by proton exchange in X-cut LN. The disks with diameters of about 5 mm and thickness of 1 mm are made from commercial Z-cut LN wafers by core drilling a cylinder and thereafter polishing the edges into a spheroidal profile. Both resonance linewidth and cavity photon lifetime measurements were performed to calculate the Q factor of the resonator, which is in excess of 108.

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

PubMed Central

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

2016-01-01

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

Expected neutrino fluence from short Gamma-Ray Burst 170817A and off-axis angle constraints

NASA Astrophysics Data System (ADS)

Biehl, D.; Heinze, J.; Winter, W.

2018-05-01

We compute the expected neutrino fluence from SGRB 170817A, associated with the gravitational wave event GW 170817, directly based on Fermi observations in two scenarios: structured jet and off-axis (observed) top-hat jet. While the expected neutrino fluence for the structured jet case is very small, large off-axis angles imply high radiation densities in the jet, which can enhance the neutrino production efficiency. In the most optimistic allowed scenario, the neutrino fluence can reach only 10-4 of the sensitivity of the neutrino telescopes. We furthermore demonstrate that the fact that gamma-rays can escape limits the baryonic loading (energy in protons versus photons) and the off-axis angle for the internal shock scenario. In particular, for a baryonic loading of 10, the off-axis angle is more strongly constrained by the baryonic loading than by the time delay between the gravitational wave event and the onset of the gamma-ray emission.

Modulation of Galactic Cosmic Rays in the Inner Heliosphere, Comparing with PAMELA Measurements

NASA Astrophysics Data System (ADS)

Qin, G.; Shen, Z.-N.

2017-09-01

We develop a numerical model to study the time-dependent modulation of galactic cosmic rays in the inner heliosphere. In the model, a time-delayed modified Parker heliospheric magnetic field (HMF) and a new diffusion coefficient model, NLGCE-F, from Qin & Zhang, are adopted. In addition, the latitudinal dependence of magnetic turbulence magnitude is assumed to be ˜ (1+{\\sin }2θ )/2 from the observations of Ulysses, and the radial dependence is assumed to be ˜ {r}S, where we choose an expression of S as a function of the heliospheric current sheet tilt angle. We show that the analytical expression used to describe the spatial variation of HMF turbulence magnitude agrees well with the Ulysses, Voyager 1, and Voyager 2 observations. By numerically calculating the modulation code, we get the proton energy spectra as a function of time during the recent solar minimum, it is shown that the modulation results are consistent with the Payload for Antimatter-Matter Exploration and Light-nuclei Astrophysics measurements.

Quantitative Assessment of Normal Fetal Brain Myelination Using Fast Macromolecular Proton Fraction Mapping.

PubMed

Yarnykh, V L; Prihod'ko, I Y; Savelov, A A; Korostyshevskaya, A M

2018-05-10

Fast macromolecular proton fraction mapping is a recently emerged MRI method for quantitative myelin imaging. Our aim was to develop a clinically targeted technique for macromolecular proton fraction mapping of the fetal brain and test its capability to characterize normal prenatal myelination. This prospective study included 41 pregnant women (gestational age range, 18-38 weeks) without abnormal findings on fetal brain MR imaging performed for clinical indications. A fast fetal brain macromolecular proton fraction mapping protocol was implemented on a clinical 1.5T MR imaging scanner without software modifications and was performed after a clinical examination with an additional scan time of <5 minutes. 3D macromolecular proton fraction maps were reconstructed from magnetization transfer-weighted, T1-weighted, and proton density-weighted images by the single-point method. Mean macromolecular proton fraction in the brain stem, cerebellum, and thalamus and frontal, temporal, and occipital WM was compared between structures and pregnancy trimesters using analysis of variance. Gestational age dependence of the macromolecular proton fraction was assessed using the Pearson correlation coefficient ( r ). The mean macromolecular proton fraction in the fetal brain structures varied between 2.3% and 4.3%, being 5-fold lower than macromolecular proton fraction in adult WM. The macromolecular proton fraction in the third trimester was higher compared with the second trimester in the brain stem, cerebellum, and thalamus. The highest macromolecular proton fraction was observed in the brain stem, followed by the thalamus, cerebellum, and cerebral WM. The macromolecular proton fraction in the brain stem, cerebellum, and thalamus strongly correlated with gestational age ( r = 0.88, 0.80, and 0.73; P < .001). No significant correlations were found for cerebral WM regions. Myelin is the main factor determining macromolecular proton fraction in brain tissues. Macromolecular proton fraction mapping is sensitive to the earliest stages of the fetal brain myelination and can be implemented in a clinical setting. © 2018 by American Journal of Neuroradiology.

PRaVDA: High Energy Physics towards proton Computed Tomography

NASA Astrophysics Data System (ADS)

Price, T.; PRaVDA Consortium

2016-07-01

Proton radiotherapy is an increasingly popular modality for treating cancers of the head and neck, and in paediatrics. To maximise the potential of proton radiotherapy it is essential to know the distribution, and more importantly the proton stopping powers, of the body tissues between the proton beam and the tumour. A stopping power map could be measured directly, and uncertainties in the treatment vastly reduce, if the patient was imaged with protons instead of conventional x-rays. Here we outline the application of technologies developed for High Energy Physics to provide clinical-quality proton Computed Tomography, in so reducing range uncertainties and enhancing the treatment of cancer.

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.

THREE-DIMENSIONAL MAGNETOHYDRODYNAMIC MODELING OF THE SOLAR WIND INCLUDING PICKUP PROTONS AND TURBULENCE TRANSPORT

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

Usmanov, Arcadi V.; Matthaeus, William H.; Goldstein, Melvyn L., E-mail: arcadi.usmanov@nasa.gov

2012-07-20

To study the effects of interstellar pickup protons and turbulence on the structure and dynamics of the solar wind, we have developed a fully three-dimensional magnetohydrodynamic solar wind model that treats interstellar pickup protons as a separate fluid and incorporates the transport of turbulence and turbulent heating. The governing system of equations combines the mean-field equations for the solar wind plasma, magnetic field, and pickup protons and the turbulence transport equations for the turbulent energy, normalized cross-helicity, and correlation length. The model equations account for photoionization of interstellar hydrogen atoms and their charge exchange with solar wind protons, energy transfermore » from pickup protons to solar wind protons, and plasma heating by turbulent dissipation. Separate mass and energy equations are used for the solar wind and pickup protons, though a single momentum equation is employed under the assumption that the pickup protons are comoving with the solar wind protons. We compute the global structure of the solar wind plasma, magnetic field, and turbulence in the region from 0.3 to 100 AU for a source magnetic dipole on the Sun tilted by 0 Degree-Sign -90 Degree-Sign and compare our results with Voyager 2 observations. The results computed with and without pickup protons are superposed to evaluate quantitatively the deceleration and heating effects of pickup protons, the overall compression of the magnetic field in the outer heliosphere caused by deceleration, and the weakening of corotating interaction regions by the thermal pressure of pickup protons.« less

Hydrated Excess Protons Can Create Their Own Water Wires.

PubMed

Peng, Yuxing; Swanson, Jessica M J; Kang, Seung-gu; Zhou, Ruhong; Voth, Gregory A

2015-07-23

Grotthuss shuttling of an excess proton charge defect through hydrogen bonded water networks has long been the focus of theoretical and experimental studies. In this work we show that there is a related process in which water molecules move ("shuttle") through a hydrated excess proton charge defect in order to wet the path ahead for subsequent proton charge migration. This process is illustrated through reactive molecular dynamics simulations of proton transport through a hydrophobic nanotube, which penetrates through a hydrophobic region. Surprisingly, before the proton enters the nanotube, it starts "shooting" water molecules into the otherwise dry space via Grotthuss shuttling, effectively creating its own water wire where none existed before. As the proton enters the nanotube (by 2-3 Å), it completes the solvation process, transitioning the nanotube to the fully wet state. By contrast, other monatomic cations (e.g., K(+)) have just the opposite effect, by blocking the wetting process and making the nanotube even drier. As the dry nanotube gradually becomes wet when the proton charge defect enters it, the free energy barrier of proton permeation through the tube via Grotthuss shuttling drops significantly. This finding suggests that an important wetting mechanism may influence proton translocation in biological systems, i.e., one in which protons "create" their own water structures (water "wires") in hydrophobic spaces (e.g., protein pores) before migrating through them. An existing water wire, e.g., one seen in an X-ray crystal structure or MD simulations without an explicit excess proton, is therefore not a requirement for protons to transport through hydrophobic spaces.

Hydrated Excess Protons Can Create Their Own Water Wires

PubMed Central

2014-01-01

Grotthuss shuttling of an excess proton charge defect through hydrogen bonded water networks has long been the focus of theoretical and experimental studies. In this work we show that there is a related process in which water molecules move (“shuttle”) through a hydrated excess proton charge defect in order to wet the path ahead for subsequent proton charge migration. This process is illustrated through reactive molecular dynamics simulations of proton transport through a hydrophobic nanotube, which penetrates through a hydrophobic region. Surprisingly, before the proton enters the nanotube, it starts “shooting” water molecules into the otherwise dry space via Grotthuss shuttling, effectively creating its own water wire where none existed before. As the proton enters the nanotube (by 2–3 Å), it completes the solvation process, transitioning the nanotube to the fully wet state. By contrast, other monatomic cations (e.g., K+) have just the opposite effect, by blocking the wetting process and making the nanotube even drier. As the dry nanotube gradually becomes wet when the proton charge defect enters it, the free energy barrier of proton permeation through the tube via Grotthuss shuttling drops significantly. This finding suggests that an important wetting mechanism may influence proton translocation in biological systems, i.e., one in which protons “create” their own water structures (water “wires”) in hydrophobic spaces (e.g., protein pores) before migrating through them. An existing water wire, e.g., one seen in an X-ray crystal structure or MD simulations without an explicit excess proton, is therefore not a requirement for protons to transport through hydrophobic spaces. PMID:25369445

Concave Reagents. 20. Sterically Shielded m-Terphenyls as Selective Agents in General Protonations(1).

PubMed

Lüning, U.; Baumgartner, H.; Manthey, C.; Meynhardt, B.

1996-11-01

New m-terphenyls with acidic substituents in the 2'-position have been used in general protonations leading to reagent-controlled selectivity enhancements: up to 96:4 for the gamma/alpha-protonation of unsymmetrically substituted allyl anions, up to 97:3 for the protonation of cyclohexyl anions generating preferentially the thermodynamically less stable cis-products. In order to allow a general, reagent-controlled protonation the acidity of the protonating agent should be as low as possible.

Differential Cross Sections for Proton-Proton Elastic Scattering

NASA Technical Reports Server (NTRS)

Norman, Ryan B.; Dick, Frank; Norbury, John W.; Blattnig, Steve R.

2009-01-01

Proton-proton elastic scattering is investigated within the framework of the one pion exchange model in an attempt to model nucleon-nucleon interactions spanning the large range of energies important to cosmic ray shielding. A quantum field theoretic calculation is used to compute both differential and total cross sections. A scalar theory is then presented and compared to the one pion exchange model. The theoretical cross sections are compared to proton-proton scattering data to determine the validity of the models.

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

Timing of electron and proton transfer in the ba(3) cytochrome c oxidase from Thermus thermophilus.

PubMed

von Ballmoos, Christoph; Lachmann, Peter; Gennis, Robert B; Ädelroth, Pia; Brzezinski, Peter

2012-06-05

Heme-copper oxidases are membrane-bound proteins that catalyze the reduction of O(2) to H(2)O, a highly exergonic reaction. Part of the free energy of this reaction is used for pumping of protons across the membrane. The ba(3) oxidase from Thermus thermophilus presumably uses a single proton pathway for the transfer of substrate protons used during O(2) reduction as well as for the transfer of the protons that are pumped across the membrane. The pumping stoichiometry (0.5 H(+)/electron) is lower than that of most other (mitochondrial-like) oxidases characterized to date (1 H(+)/electron). We studied the pH dependence and deuterium isotope effect of the kinetics of electron and proton transfer reactions in the ba(3) oxidase. The results from these studies suggest that the movement of protons to the catalytic site and movement to a site located some distance from the catalytic site [proposed to be a "proton-loading site" (PLS) for pumped protons] are separated in time, which allows individual investigation of these reactions. A scenario in which the uptake and release of a pumped proton occurs upon every second transfer of an electron to the catalytic site would explain the decreased proton pumping stoichiometry compared to that of mitochondrial-like oxidases.

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2013-04-05

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

4D dose calculation and delivery with interplay effects between respiratory motion and uniform scanning proton beam

NASA Astrophysics Data System (ADS)

Zhao, Qingya

2011-12-01

Proton radiotherapy has advantages to deliver accurate high conformal radiation dose to the tumor while sparing the surrounding healthy tissue and critical structures. However, the treatment effectiveness is degraded greatly due to patient free breathing during treatment delivery. Motion compensation for proton radiotherapy is especially challenging as proton beam is more sensitive to the density change along the beam path. Tumor respiratory motion during treatment delivery will affect the proton dose distribution and the selection of optimized parameters for treatment planning, which has not been fully addressed yet in the existing approaches for proton dose calculation. The purpose of this dissertation is to develop an approach for more accurate dose delivery to a moving tumor in proton radiotherapy, i.e., 4D proton dose calculation and delivery, for the uniform scanning proton beam. A three-step approach has been carried out to achieve this goal. First, a solution for the proton output factor calculation which will convert the prescribed dose to machine deliverable monitor unit for proton dose delivery has been proposed and implemented. The novel sector integration method is accurate and time saving, which considers the various beam scanning patterns and treatment field parameters, such as aperture shape, aperture size, measuring position, beam range, and beam modulation. Second, tumor respiratory motion behavior has been statistically characterized and the results have been applied to advanced image guided radiation treatment. Different statistical analysis and correlation discovery approaches have been investigated. The internal / external motion correlation patterns have been simulated, analyzed, and applied in a new hybrid gated treatment to improve the target coverage. Third, a dose calculation method has been developed for 4D proton treatment planning which integrates the interplay effects of tumor respiratory motion patterns and proton beam delivery mechanism. These three steps provide an innovative integrated framework for accurate 4D proton dose calculation and treatment planning for a moving tumor, which extends the functionalities of existing 3D planning systems. In short, this dissertation work addresses a few important problems for effective proton radiotherapy to a moving target. The outcomes of the dissertation are very useful for motion compensation with advanced image guided proton treatment.

Proton-Coupled Electron Transfer in Artificial Photosynthetic Systems.

PubMed

Mora, S Jimena; Odella, Emmanuel; Moore, Gary F; Gust, Devens; Moore, Thomas A; Moore, Ana L

2018-02-20

Artificial photosynthetic constructs can in principle operate more efficiently than natural photosynthesis because they can be rationally designed to optimize solar energy conversion for meeting human demands rather than the multiple needs of an organism competing for growth and reproduction in a complex ecosystem. The artificial photosynthetic constructs described in this Account consist primarily of covalently linked synthetic chromophores, electron donors and acceptors, and proton donors and acceptors that carry out the light absorption, electron transfer, and proton-coupled electron transfer (PCET) processes characteristic of photosynthetic cells. PCET is the movement of an electron from one site to another accompanied by proton transfer. PCET and the transport of protons over tens of angstroms are important in all living cells because they are a fundamental link between redox processes and the establishment of transmembrane gradients of proton electrochemical potential, known as proton-motive force (PMF), which is the unifying concept in bioenergetics. We have chosen a benzimidazole phenol (BIP) system as a platform for the study of PCET because with appropriate substitutions it is possible to design assemblies in which one or multiple proton transfers can accompany oxidation of the phenol. In BIP, oxidation of the phenol increases its acidity by more than ten pK a units; thus, electrochemical oxidation of the phenol is associated with a proton transfer to the imidazole. This is an example of a PCET process involving transfer of one electron and one proton, known as electron-proton transfer (EPT). When the benzimidazole moiety of BIP is substituted at the 4-position with good proton acceptor groups such as aliphatic amines, experimental and theoretical results indicate that two proton transfers occur upon one-electron oxidation of the phenol. This phenomenon is described as a one-electron-two-proton transfer (E2PT) process and results in translocation of protons over ∼7 Å via a Grotthuss-type mechanism, where the protons traverse a network of internally H-bonded sites. In the case of the E2TP process involving BIP analogues with amino group substituents, the thermodynamic price paid in redox potential to move a proton to the final proton acceptor is ∼300 mV. In this example, the decrease in redox potential limits the oxidizing power of the resulting phenoxyl radical. Thus, unlike the biological counterpart, the artificial construct is thermodynamically incapable of effectively advancing the redox state of a water oxidation catalyst. The design of systems where multiple proton transfer events are coupled to an oxidation reaction while a relatively high redox potential is maintained remains an outstanding challenge. The ability to control proton transfer and activity at defined distances and times is key to achieving proton management in the vicinity of catalysts operating at low overpotential in myriad biochemically important processes. Artificial photosynthetic constructs with well-defined structures, such as the ones described in this Account, can provide the means for discovering design principles upon which efficient redox catalysts for electrolysis and fuel cells can be based.

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.

Lateral Diffusion Length Changes in HgCdTe Detectors in a Proton Environment

NASA Technical Reports Server (NTRS)

Hubbs, John E.; Marshall, Paul W.; Marshall, Cheryl J.; Gramer, Mark E.; Maestas, Diana; Garcia, John P.; Dole, Gary A.; Anderson, Amber A.

2007-01-01

This paper presents a study of the performance degradation in a proton environment of very long wavelength infrared (VLWIR) HgCdTe detectors. The energy dependence of the Non-Ionizing Energy Loss (NIEL) in HgCdTe provides a framework for estimating the responsivity degradation in VLWIR HgCdTe due to on orbit exposure from protons. Banded detector arrays that have different detector designs were irradiated at proton energies of 7, 12, and 63 MeV. These banded detector arrays allovedin sight into how the fundamental detector parameters degraded in a proton environment at the three different proton energies. Measured data demonstrated that the detector responsivity degradation at 7 MeV is 5 times larger than the degradation at 63 MeV. The comparison of the responsivity degradation at the different proton energies suggests that the atomic Columbic interaction of the protons with the HgCdTe detector is likely the primary mechanism responsible for the degradation in responsivity at proton energies below 30 MeV.

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.

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.

Response functions of Fuji imaging plates to monoenergetic protons in the energy range 0.6-3.2 MeV

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

Bonnet, T.; Denis-Petit, D.; Gobet, F.

2013-01-15

We have measured the responses of Fuji MS, SR, and TR imaging plates (IPs) to protons with energies ranging from 0.6 to 3.2 MeV. Monoenergetic protons were produced with the 3.5 MV AIFIRA (Applications Interdisciplinaires de Faisceaux d'Ions en Region Aquitaine) accelerator at the Centre d'Etudes Nucleaires de Bordeaux Gradignan (CENBG). The IPs were irradiated with protons backscattered off a tantalum target. We present the photo-stimulated luminescence response of the IPs together with the fading measurements for these IPs. A method is applied to allow correction of fading effects for variable proton irradiation duration. Using the IP fading corrections, amore » model of the IP response function to protons was developed. The model enables extrapolation of the IP response to protons up to proton energies of 10 MeV. Our work is finally compared to previous works conducted on Fuji TR IP response to protons.« less

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.

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

Spectral Analyses and Radiation Exposures from Several Ground-Level Enhancement (GLE) Solar Proton Events: A Comparison of Methodologies

NASA Technical Reports Server (NTRS)

Atwell, William; Tylka, Allan; Dietrich, William; Badavi, Francis; Rojdev, Kristina

2011-01-01

Several methods for analyzing the particle spectra from extremely large solar proton events, called Ground-Level Enhancements (GLEs), have been developed and utilized by the scientific community to describe the solar proton energy spectra and have been further applied to ascertain the radiation exposures to humans and radio-sensitive systems, namely electronics. In this paper 12 GLEs dating back to 1956 are discussed, and the three methods for describing the solar proton energy spectra are reviewed. The three spectral fitting methodologies are EXP [an exponential in proton rigidity (R)], WEIB [Weibull fit: an exponential in proton energy], and the Band function (BAND) [a double power law in proton rigidity]. The EXP and WEIB methods use low energy (MeV) GLE solar proton data and make extrapolations out to approx.1 GeV. On the other hand, the BAND method utilizes low- and medium-energy satellite solar proton data combined with high-energy solar proton data deduced from high-latitude neutron monitoring stations. Thus, the BAND method completely describes the entire proton energy spectrum based on actual solar proton observations out to 10 GeV. Using the differential spectra produced from each of the 12 selected GLEs for each of the three methods, radiation exposures are presented and discussed in detail. These radiation exposures are then compared with the current 30-day and annual crew exposure limits and the radiation effects to electronics.

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

PubMed Central

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

2014-01-01

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

Proton Radiography Imager:Generates Synthetic Proton Radiographs

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

Wilks, Scott C.; Black, Mason R.

ProRad is a computer program that is used to generate synthetic images of proton (or other charged particles) radiographs. The proton radiographs arc images that arc obtained by sending energetic protons (or electrons or positrons, for example) through 11 plasma where electric and/or magnetic fields alter the particles trajectory, Dnd the variations me imaged on RC film, image plate, or equivalent

Isomers and conformational barriers of gas phase nicotine, nornicotine and their protonated forms

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

Yoshida, Tomoki; Farone, William A.; Xantheas, Sotiris S.

We report extensive conformational searches of the neutral nicotine, nornicotine and their protonated analogs that are based on ab-initio second order Møller-Plesset perturbation (MP2) electronic structure calculations. Initial searches were performed with the 6-31G(d,p) and the energetics of the most important structures were further refined from geometry optimizations with the aug-cc-pVTZ basis set. Based on the calculated free energies at T=298 K for the gas phase molecules, neutral nicotine has two dominant trans conformers, whereas neutral nornicotine is a mixture of several conformers. For nicotine, the protonation on both the pyridine and the pyrrolidine sites is energetically competitive, whereas nornicotinemore » prefers protonation on the pyridine nitrogen. The protonated form of nicotine is mainly a mixture of two pyridine-protonated trans conformers and two pyrrolidine-protonated trans conformers, whereas the protonated form of nornicotine is a mixture of four pyridine-protonated trans conformers. Nornicotine is conformationally more flexible than nicotine, however it is less protonated at the biologically important pyrrolidine nitrogen site. The lowest energy isomers for each case were found to interconvert via low (< 6 kcal/mol) rotational barriers around the pyridine-pyrrolidine bond.« less

Transverse relaxation of scalar-coupled protons.

PubMed

Segawa, Takuya F; Baishya, Bikash; Bodenhausen, Geoffrey

2010-10-25

In a preliminary communication (B. Baishya, T. F. Segawa, G. Bodenhausen, J. Am. Chem. Soc. 2009, 131, 17538-17539), we recently demonstrated that it is possible to obtain clean echo decays of protons in biomolecules despite the presence of homonuclear scalar couplings. These unmodulated decays allow one to determine apparent transverse relaxation rates R(2) (app) of individual protons. Herein, we report the observation of R(2) (app) for three methyl protons, four amide H(N) protons, and all 11 backbone H(α) protons in cyclosporin A. If the proton resonances overlap, their R(2) (app) rates can be measured by transferring their magnetization to neighboring (13)C nuclei, which are less prone to overlap. The R(2) (app) rates of protons attached to (13)C are faster than those attached to (12)C because of (13)C-(1)H dipolar interactions. The differences of these rates allow the determination of local correlation functions. Backbone H(N) and H(α) protons that have fast decay rates R(2) (app) also feature fast longitudinal relaxation rates R(1) and intense NOESY cross peaks that are typical of crowded environments. Variations of R(2) (app) rates of backbone H(α) protons in similar amino acids reflect differences in local environments.

Luminescence imaging of water during proton-beam irradiation for range estimation

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

Yamamoto, Seiichi, E-mail: s-yama@met.nagoya-u.ac.jp; Okumura, Satoshi; Komori, Masataka

Purpose: Proton therapy has the ability to selectively deliver a dose to the target tumor, so the dose distribution should be accurately measured by a precise and efficient method. The authors found that luminescence was emitted from water during proton irradiation and conjectured that this phenomenon could be used for estimating the dose distribution. Methods: To achieve more accurate dose distribution, the authors set water phantoms on a table with a spot scanning proton therapy system and measured the luminescence images of these phantoms with a high-sensitivity, cooled charge coupled device camera during proton-beam irradiation. The authors imaged the phantomsmore » of pure water, fluorescein solution, and an acrylic block. Results: The luminescence images of water phantoms taken during proton-beam irradiation showed clear Bragg peaks, and the measured proton ranges from the images were almost the same as those obtained with an ionization chamber. Furthermore, the image of the pure-water phantom showed almost the same distribution as the tap-water phantom, indicating that the luminescence image was not related to impurities in the water. The luminescence image of the fluorescein solution had ∼3 times higher intensity than water, with the same proton range as that of water. The luminescence image of the acrylic phantom had a 14.5% shorter proton range than that of water; the proton range in the acrylic phantom generally matched the calculated value. The luminescence images of the tap-water phantom during proton irradiation could be obtained in less than 2 s. Conclusions: Luminescence imaging during proton-beam irradiation is promising as an effective method for range estimation in proton therapy.« less

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.

Excited state of protonated benzene and toluene

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

Esteves-López, Natalia; Dedonder-Lardeux, Claude; Jouvet, Christophe, E-mail: Christophe.jouvet@univ-amu.fr

We present photo-fragmentation electronic spectra of the simplest protonated aromatic molecules, protonated benzene and toluene, recorded under medium resolution conditions and compared with the photo-fragmentation spectrum of protonated pyridine. Despite the resolution and cold temperature achieved in the experiment, the electronic spectra of protonated benzene and toluene are structure-less, thus intrinsically broadened. This is in agreement with the large geometrical changes and the fast dynamic toward internal conversion predicted by ab initio calculations for protonated benzene [Rode et al., J. Phys. Chem. A 113, 5865–5873 (2009)].

Froissart bound and self-similarity based models of proton structure functions

NASA Astrophysics Data System (ADS)

Choudhury, D. K.; Saikia, Baishali

2018-03-01

Froissart bound implies that the total proton-proton cross-section (or equivalently proton structure function) cannot rise faster than log2s ˜log2 1 x. Compatibility of such behavior with the notion of self-similarity in proton structure function was suggested by us sometime back. In the present work, we generalize and improve it further by considering more recent self-similarity based models of proton structure functions and compare with recent data as well as with the model of Block, Durand, Ha and McKay.

Accelerator driven sub-critical core

DOEpatents

McIntyre, Peter M; Sattarov, Akhdiyor

2015-03-17

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

Radiosensitivity of human ovarian carcinoma and melanoma cells to γ-rays and protons

PubMed Central

Keta, Otilija; Todorović, Danijela; Popović, Nataša; Korićanac, Lela; Cuttone, Giacomo; Petrović, Ivan

2014-01-01

Introduction Proton radiation offers physical advantages over conventional radiation. Radiosensitivity of human 59M ovarian cancer and HTB140 melanoma cells was investigated after exposure to γ-rays and protons. Material and methods Irradiations were performed in the middle of a 62 MeV therapeutic proton spread out Bragg peak with doses ranging from 2 to 16 Gy. The mean energy of protons was 34.88 ±2.15 MeV, corresponding to the linear energy transfer of 4.7 ±0.2 keV/µm. Irradiations with γ-rays were performed using the same doses. Viability, proliferation and survival were assessed 7 days after both types of irradiation while analyses of cell cycle and apoptosis were performed 48 h after irradiation. Results Results showed that γ-rays and protons reduced the number of viable cells for both cell lines, with stronger inactivation achieved after irradiation with protons. Surviving fractions for 59M were 0.91 ±0.01 for γ-rays and 0.81 ±0.01 for protons, while those for HTB140 cells were 0.93 ±0.01 for γ-rays and 0.86 ±0.01 for protons. Relative biological effectiveness of protons, being 2.47 ±0.22 for 59M and 2.08 ±0.36 for HTB140, indicated that protons provoked better cell elimination than γ-rays. After proton irradiation proliferation capacity of the two cell lines was slightly higher as compared to γ-rays. Proliferation was higher for 59M than for HTB140 cells after both types of irradiation. Induction of apoptosis and G2 arrest detected after proton irradiation were more prominent in 59M cells. Conclusions The obtained results suggest that protons exert better antitumour effects on ovarian carcinoma and melanoma cells than γ-rays. The dissimilar response of these cells to radiation is related to their different features. PMID:25097591

Estimation of stopped protons at energies relevant for a beam energy scan at the BNL Relativistic Heavy Ion Collider

NASA Astrophysics Data System (ADS)

Thakur, Dhananjaya; Jakhar, Sunil; Garg, Prakhar; Sahoo, Raghunath

2017-04-01

The recent net-proton fluctuation results of the STAR (Solenoidal Tracker At RHIC) experiment from the beam energy scan (BES) program at the BNL Relativistic Heavy Ion Collider (RHIC) have drawn much attention to exploring the QCD critical point and the nature of deconfinement phase transition. There has been much speculation that the nonmonotonic behavior of κ σ2 of the produced protons around √{sN N} = 19.6 GeV in the STAR results may be due to the existence of a QCD critical point. However, the experimentally measured proton distributions contain protons from heavy resonance decays, from baryon stopping, and from direct production processes. These proton distributions are used to estimate the net-proton number fluctuation. Because it is difficult to disentangle the protons from the above-mentioned sources, it is better to devise a method which will account for the directly produced baryons (protons) to study the dynamical fluctuation at different center-of-mass energies. This is because it is assumed that any associated criticality in the system could affect the particle production mechanism and hence the dynamical fluctuation in various conserved numbers. In the present work, we demonstrate a method to estimate the number of stopped protons at RHIC BES energies for central 0-5% Au +Au collisions within STAR acceptance and discuss its implications on the net-proton fluctuation results.

Pencil beam scanning proton therapy vs rotational arc radiation therapy: A treatment planning comparison for postoperative oropharyngeal cancer

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

Apinorasethkul, Ontida, E-mail: Ontida.a@gmail.com; Kirk, Maura; Teo, Kevin

Patients diagnosed with head and neck cancer are traditionally treated with photon radiotherapy. Proton therapy is currently being used clinically and may potentially reduce treatment-related toxicities by minimizing the dose to normal organs in the treatment of postoperative oropharyngeal cancer. The finite range of protons has the potential to significantly reduce normal tissue toxicity compared to photon radiotherapy. Seven patients were planned with both proton and photon modalities. The planning goal for both modalities was achieving the prescribed dose to 95% of the planning target volume (PTV). Dose-volume histograms were compared in which all cases met the target coverage goals.more » Mean doses were significantly lower in the proton plans for the oral cavity (1771 cGy photon vs 293 cGy proton, p < 0.001), contralateral parotid (1796 cGy photon vs 1358 proton, p < 0.001), and the contralateral submandibular gland (3608 cGy photon vs 3251 cGy proton, p = 0.03). Average total integral dose was 9.1% lower in proton plans. The significant dosimetric sparing seen with proton therapy may lead to reduced side effects such as pain, weight loss, taste changes, and dry mouth. Prospective comparisons of protons vs photons for disease control, toxicity, and patient-reported outcomes are therefore warranted and currently being pursued.« less

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.

High-energy proton imaging for biomedical applications

DOE PAGES

Prall, Matthias; Durante, Marco; Berger, Thomas; ...

2016-06-10

The charged particle community is looking for techniques exploiting proton interactions instead of X-ray absorption for creating images of human tissue. Due to multiple Coulomb scattering inside the measured object it has shown to be highly non-trivial to achieve sufficient spatial resolution. We present imaging of biological tissue with a proton microscope. This device relies on magnetic optics, distinguishing it from most published proton imaging methods. For these methods reducing the data acquisition time to a clinically acceptable level has turned out to be challenging. In a proton microscope, data acquisition and processing are much simpler. This device even allowsmore » imaging in real time. The primary medical application will be image guidance in proton radiosurgery. Proton images demonstrating the potential for this application are presented. As a result, tomographic reconstructions are included to raise awareness of the possibility of high-resolution proton tomography using magneto-optics.« less

Generation of quasi-monoenergetic protons from a double-species target driven by the radiation pressure of an ultraintense laser pulse

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

Pae, Ki Hong; Kim, Chul Min, E-mail: chulmin@gist.ac.kr; Advanced Photonics Research Institute, Gwangju Institute of Science and Technology, Gwangju 61005

In laser-driven proton acceleration, generation of quasi-monoenergetic proton beams has been considered a crucial feature of the radiation pressure acceleration (RPA) scheme, but the required difficult physical conditions have hampered its experimental realization. As a method to generate quasi-monoenergetic protons under experimentally viable conditions, we investigated using double-species targets of controlled composition ratio in order to make protons bunched in the phase space in the RPA scheme. From a modified optimum condition and three-dimensional particle-in-cell simulations, we showed by varying the ion composition ratio of proton and carbon that quasi-monoenergetic protons could be generated from ultrathin plane targets irradiated withmore » a circularly polarized Gaussian laser pulse. The proposed scheme should facilitate the experimental realization of ultrashort quasi-monoenergetic proton beams for unique applications in high field science.« less

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.

High-energy proton imaging for biomedical applications

NASA Astrophysics Data System (ADS)

Prall, M.; Durante, M.; Berger, T.; Przybyla, B.; Graeff, C.; Lang, P. M.; Latessa, C.; Shestov, L.; Simoniello, P.; Danly, C.; Mariam, F.; Merrill, F.; Nedrow, P.; Wilde, C.; Varentsov, D.

2016-06-01

The charged particle community is looking for techniques exploiting proton interactions instead of X-ray absorption for creating images of human tissue. Due to multiple Coulomb scattering inside the measured object it has shown to be highly non-trivial to achieve sufficient spatial resolution. We present imaging of biological tissue with a proton microscope. This device relies on magnetic optics, distinguishing it from most published proton imaging methods. For these methods reducing the data acquisition time to a clinically acceptable level has turned out to be challenging. In a proton microscope, data acquisition and processing are much simpler. This device even allows imaging in real time. The primary medical application will be image guidance in proton radiosurgery. Proton images demonstrating the potential for this application are presented. Tomographic reconstructions are included to raise awareness of the possibility of high-resolution proton tomography using magneto-optics.

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

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

Infrared photodissociation spectroscopy of protonated neurotransmitters in the gas phase

NASA Astrophysics Data System (ADS)

MacLeod, N. A.; Simons, J. P.

2007-03-01

Protonated neurotransmitters have been produced in the gas phase via a novel photochemical scheme: complexes of the species of interest, 1-phenylethylamine, 2-amino-1-phenylethanol and the diastereo-isomers, ephedrine and pseudoephedrine, with a suitable proton donor, phenol (or indole), are produced in a supersonic expansion and ionized by resonant two photon ionization of the donor. Efficient proton transfer generates the protonated neurotransmitters, complexed to a phenoxy radical. Absorption of infrared radiation, and subsequent evaporation of the phenoxy tag, coupled with time of flight mass spectrometry, provides vibrational spectra of the protonated (and also hydrated) complexes for comparison with the results of quantum chemical computation. Comparison with the conformational structures of the neutral neurotransmitters (established previously) reveals the effect of protonation on their structure. The photochemical proton transfer strategy allows spectra to be recorded from individual laser shots and their quality compares favourably with that obtained using electro-spray or matrix assisted laser desorption ion sources.

Design of a proton microbeam of the PEFP

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

Kim, Kye Ryung; Kim, Yong Hwan; Chang, Ji Ho

2008-02-15

The PEFP has been developing a 100 MeV proton linear accelerator and user facilities for 20 and 100 MeV proton beams. At one end of the five 20 MeV proton beam lines, a proton microbeam construction was considered for an application in the fields of material, biological, and medical sciences. To develop the proton microbeam, realization of a few MeV proton beam with a few tens of microamperes in diameter of a beam spot was essentially required. In this report, the basic descriptions of the proton microbeam which is composed of an energy degrader, slits, magnetic lens, a target chamber,more » and detectors are presented including a consideration of unfavorable aspects concerning some specific characteristics of a linear accelerator, such as pulse mode operation and fixed energy. Some calculation results from a Monte Carlo simulation by using the SRIM2006 and the TURTLE codes are also included.« less

High-energy proton imaging for biomedical applications

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

Prall, Matthias; Durante, Marco; Berger, Thomas

The charged particle community is looking for techniques exploiting proton interactions instead of X-ray absorption for creating images of human tissue. Due to multiple Coulomb scattering inside the measured object it has shown to be highly non-trivial to achieve sufficient spatial resolution. We present imaging of biological tissue with a proton microscope. This device relies on magnetic optics, distinguishing it from most published proton imaging methods. For these methods reducing the data acquisition time to a clinically acceptable level has turned out to be challenging. In a proton microscope, data acquisition and processing are much simpler. This device even allowsmore » imaging in real time. The primary medical application will be image guidance in proton radiosurgery. Proton images demonstrating the potential for this application are presented. As a result, tomographic reconstructions are included to raise awareness of the possibility of high-resolution proton tomography using magneto-optics.« 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.

Influence of the Proton Pressure Tensor on the Turbulent Velocity Spectrum at Ion Kinetic Scales

NASA Astrophysics Data System (ADS)

Vasquez, B. J.; Markovskii, S.

2011-12-01

Numerical hybrid simulations with particle protons and fluid electrons are presented for turbulent fluctuations with spatial variations in a plane perpendicular to the background magnetic field. The steepened portion of the proton bulk velocity spectrum is found at smaller wavenumbers for larger background proton temperature. The velocity spectrum is determined, in part, by the proton pressure tensor. The proton pressure tensor is shown to possess non-gyrotropic and finite off-diagonal components in the places where the turbulent fluctuations have developed strong gradients. Proton demagnetization at these places is a factor in the departure from a Maxwellian velocity distribution function. How demagnetization could connect with both reversible and effectively irreversible aspects of the pressure tensor is considered. The effectively irreversible aspect corresponds to the net heating of the protons and to the dissipation of the turbulent energy cascade.

Proton Therapy for Head and Neck Cancer.

PubMed

Kim, Joseph K; Leeman, Jonathan E; Riaz, Nadeem; McBride, Sean; Tsai, Chiaojung Jillian; Lee, Nancy Y

2018-05-09

The application of proton beam radiation therapy in the treatment of head and neck cancer has grown tremendously in the past few years. Globally, widespread interest in proton beam therapy has led to multiple research efforts regarding its therapeutic value and cost-effectiveness. The current standard of care using modern photon radiation technology has demonstrated excellent treatment outcomes, yet there are some situations where disease control remains suboptimal with the potential for detrimental acute and chronic toxicities. Due to the advantageous physical properties of the proton beam, proton beam therapy may be superior to photon therapy in some patient subsets for both disease control and patient quality of life. As enthusiasm and excitement for proton beam therapy continue to increase, clinical research and widespread adoption will elucidate the true value of proton beam therapy and give a greater understanding of the full risks and benefits of proton therapy in head and neck cancer.

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

NASA Technical Reports Server (NTRS)

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

1979-01-01

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

Long-range multiplicity correlations in proton-proton collisions

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

Bzdak, Adam

The forward-backward long-range multiplicity correlations in proton-proton collisions are investigated in the model with two independent sources of particles: one left- and one right-moving wounded nucleon. A good agreement with the UA5 Collaboration proton-antiproton data at the c.m. energy of 200 GeV is observed. For comparison the model with only one source of particles is also discussed.

Proton therapy - Present and future.

PubMed

Mohan, Radhe; Grosshans, David

2017-01-15

In principle, proton therapy offers a substantial clinical advantage over conventional photon therapy. This is because of the unique depth-dose characteristics of protons, which can be exploited to achieve significant reductions in normal tissue doses proximal and distal to the target volume. These may, in turn, allow escalation of tumor doses and greater sparing of normal tissues, thus potentially improving local control and survival while at the same time reducing toxicity and improving quality of life. Protons, accelerated to therapeutic energies ranging from 70 to 250MeV, typically with a cyclotron or a synchrotron, are transported to the treatment room where they enter the treatment head mounted on a rotating gantry. The initial thin beams of protons are spread laterally and longitudinally and shaped appropriately to deliver treatments. Spreading and shaping can be achieved by electro-mechanical means to treat the patients with "passively-scattered proton therapy" (PSPT) or using magnetic scanning of thin "beamlets" of protons of a sequence of initial energies. The latter technique can be used to treat patients with optimized intensity modulated proton therapy (IMPT), the most powerful proton modality. Despite the high potential of proton therapy, the clinical evidence supporting the broad use of protons is mixed. It is generally acknowledged that proton therapy is safe, effective and recommended for many types of pediatric cancers, ocular melanomas, chordomas and chondrosarcomas. Although promising results have been and continue to be reported for many other types of cancers, they are based on small studies. Considering the high cost of establishing and operating proton therapy centers, questions have been raised about their cost effectiveness. General consensus is that there is a need to conduct randomized trials and/or collect outcomes data in multi-institutional registries to unequivocally demonstrate the advantage of protons. Treatment planning and plan evaluation of PSPT and IMPT require special considerations compared to the processes used for photon treatment planning. The differences in techniques arise from the unique physical properties of protons but are also necessary because of the greater vulnerability of protons to uncertainties, especially from inter- and intra-fractional variations in anatomy. These factors must be considered in designing as well as evaluating treatment plans. In addition to anatomy variations, other sources of uncertainty in dose delivered to the patient include the approximations and assumptions of models used for computing dose distributions for planning of treatments. Furthermore, the relative biological effectiveness (RBE) of protons is simplistically assumed to have a constant value of 1.1. In reality, the RBE is variable and a complex function of the energy of protons, dose per fraction, tissue and cell type, end point, etc. These uncertainties, approximations and current technological limitations of proton therapy may limit the achievement of its true potential. Ongoing research is aimed at better understanding the consequences of the various uncertainties on proton therapy and reducing the uncertainties through image-guidance, adaptive radiotherapy, further study of biological properties of protons and the development of novel dose computation and optimization methods. However, residual uncertainties will remain in spite of the best efforts. To increase the resilience of dose distributions in the face of uncertainties and improve our confidence in dose distributions seen on treatment plans, robust optimization techniques are being developed and implemented. We assert that, with such research, proton therapy will be a commonly applied radiotherapy modality for most types of solid cancers in the near future. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation, characterization and application of novel proton conducting ceramics

NASA Astrophysics Data System (ADS)

Wang, Siwei

Due to the immediate energy shortage and the requirement of environment protection nowadays, the efficient, effective and environmental friendly use of current energy sources is urgent. Energy conversion and storage is thus an important focus both for industry and academia. As one of the hydrogen energy related materials, proton conducting ceramics can be applied in solid oxide fuel cells and steam electrolysers, as well as high temperature hydrogen separation membranes and hydrogen sensors. For most of the practical applications, both high proton conductivity and chemical stability are desirable. However, the state-of-the-art proton conducting ceramics are facing great challenges in simultaneously fulfilling conductivity and stability requirements for practical applications. Consequently, understanding the properties for the proton conducting ceramics and developing novel materials that possess both high proton conductivity and enhanced chemical stability have both scientific and practical significances. The objective of this study is to develop novel proton conducting ceramics, either by evaluating the doping effects on the state-of-the-art simple perovskite structured barium cerates, or by investigating novel complex perovskite structured Ba3Ca1.18Nb1.82O 9-delta based proton conductors as potential proton conducting ceramics with improved proton conductivity and enhanced chemical stability. Different preparation methods were compared, and their influence on the structure, including the bulk and grain boundary environment has been investigated. In addition, the effects of microstructure on the electrical properties of the proton conducting ceramics have also been characterized. The solid oxide fuel cell application for the proton conducting ceramics performed as electrolyte membranes has been demonstrated.

Multiscale Simulations Reveal Key Aspects of the Proton Transport Mechanism in the ClC-ec1 Antiporter

PubMed Central

Lee, Sangyun; Swanson, Jessica M.J.; Voth, Gregory A.

2016-01-01

Multiscale reactive molecular dynamics simulations are used to study proton transport through the central region of ClC-ec1, a widely studied ClC transporter that enables the stoichiometric exchange of 2 Cl– ions for 1 proton (H+). It has long been known that both Cl– and proton transport occur through partially congruent pathways, and that their exchange is strictly coupled. However, the nature of this coupling and the mechanism of antiporting remain topics of debate. Here multiscale simulations have been used to characterize proton transport between E203 (Gluin) and E148 (Gluex), the internal and external intermediate proton binding sites, respectively. Free energy profiles are presented, explicitly accounting for the binding of Cl– along the central pathway, the dynamically coupled hydration changes of the central region, and conformational changes of Gluin and Gluex. We find that proton transport between Gluin and Gluex is possible in both the presence and absence of Cl– in the central binding site, although it is facilitated by the anion presence. These results support the notion that the requisite coupling between Cl– and proton transport occurs elsewhere (e.g., during proton uptake or release). In addition, proton transport is explored in the E203K mutant, which maintains proton permeation despite the substitution of a basic residue for Gluin. This collection of calculations provides for the first time, to our knowledge, a detailed picture of the proton transport mechanism in the central region of ClC-ec1 at a molecular level. PMID:27028643

Proton Radiotherapy for Childhood Ependymoma: Initial Clinical Outcomes and Dose Comparisons

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

MacDonald, Shannon M.; Safai, Sairos; Trofimov, Alexei

2008-07-15

Purpose: To report preliminary clinical outcomes for pediatric patients treated with proton beam radiation for intracranial ependymoma and compare the dose distributions of intensity-modulated radiation therapy with photons (IMRT), three-dimensional conformal proton radiation, and intensity-modulated proton radiation therapy (IMPT) for representative patients. Methods and Materials: All children with intracranial ependymoma confined to the supratentorial or infratentorial brain treated at the Francis H. Burr Proton Facility and Harvard Cyclotron between November 2000 and March 2006 were included in this study. Seventeen patients were treated with protons. Proton, IMRT, and IMPT plans were generated with similar clinical constraints for representative infratentorial andmore » supratentorial ependymoma cases. Tumor and normal tissue dose-volume histograms were calculated and compared. Results: At a median follow-up of 26 months from the start date of radiation therapy, local control, progression-free survival, and overall survival rates were 86%, 80%, and 89%, respectively. Subtotal resection was significantly associated with decreased local control (p = 0.016). Similar tumor volume coverage was achieved with IMPT, proton therapy, and IMRT. Substantial normal tissue sparing was seen with proton therapy compared with IMRT. Use of IMPT will allow for additional sparing of some critical structures. Conclusions: Preliminary disease control with proton therapy compares favorably with the literature. Dosimetric comparisons show the advantage of proton radiation compared with IMRT in the treatment of ependymoma. Further sparing of normal structures appears possible with IMPT. Superior dose distributions were accomplished with fewer beam angles with the use of protons and IMPT.« less

Protonation of Excited State Pyrene-1-Carboxylate by Phosphate and Organic Acids in Aqueous Solution Studied by Fluorescence Spectroscopy

PubMed Central

Zelent, Bogumil; Vanderkooi, Jane M.; Coleman, Ryan G.; Gryczynski, Ignacy; Gryczynski, Zygmunt

2006-01-01

Pyrene-1-carboxylic acid has a pK of 4.0 in the ground state and 8.1 in the singlet electronic excited state. In the pH range of physiological interest (pH ∼5–8), the ground state compound is largely ionized as pyrene-1-carboxylate, but protonation of the excited state molecule occurs when a proton donor reacts with the carboxylate during the excited state lifetime of the fluorophore. Both forms of the pyrene derivatives are fluorescent, and in this work the protonation reaction was measured by monitoring steady-state and time-resolved fluorescence. The rate of protonation of pyrene-COO− by acetic, chloroacetic, lactic, and cacodylic acids is a function of ΔpK, as predicted by Marcus theory. The rate of proton transfer from these acids saturates at high concentration, as expected for the existence of an encounter complex. Trihydrogen-phosphate is a much better proton donor than dihydrogen- and monohydrogen-phosphate, as can be seen by the pH dependence. The proton-donating ability of phosphate does not saturate at high concentrations, but increases with increasing phosphate concentration. We suggest that enhanced rate of proton transfer at high phosphate concentrations may be due to the dual proton donating and accepting nature of phosphate, in analogy to the Grotthuss mechanism for proton transfer in water. It is suggested that in molecular structures containing multiple phosphates, such as membrane surfaces and DNA, proton transfer rates will be enhanced by this mechanism. PMID:16920831

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

Proton therapy for locally advanced breast cancer: A systematic review of the literature.

PubMed

Kammerer, Emmanuel; Guevelou, Jennifer Le; Chaikh, Abdulhamid; Danhier, Serge; Geffrelot, Julien; Levy, Christelle; Saloux, Eric; Habrand, Jean-Louis; Thariat, Juliette

2018-02-01

Radiation therapy plays a major role in the management of adjuvant breast cancer with nodal involvement, with an iatrogenic increase of cardio-vascular risk. Photon therapy, even with intensity modulation, has the downsides of high mean heart dose and heterogeneous target coverage, particularly in the case of internal mammary irradiation. This systematic review of the literature aims to evaluate proton therapy in locally advanced breast cancer. PubMed was searched for original full-text articles with the following search terms: «Proton Therapy» and «Breast Cancer». On-going trials were collected using the words "Breast Cancer" and "Protons". 13 articles met the criteria: 6 with passive proton therapy (Double Scattering), 5 with Pencil Beam Scanning (PBS) and 2 with a combination of both. Proton therapy offered a better target coverage than photons, even compared with intensity modulation radiation therapy (including static or rotational IMRT or tomotherapy). With proton therapy, volumes receiving 95% of the dose were around 98%, with low volumes receiving 105% of the dose. Proton therapy often decreased mean heart dose by a factor of 2 or 3, i.e. 1 Gy with proton therapy versus 3 Gy with conventional 3D, and 6 Gy for IMRT. Lungs were better spared with proton therapy than with photon therapy. Cutaneous toxicity observed with double scattering is improved with PBS. Proton therapy reduces mean heart dose in breast cancer irradiation, probably reducing late cardio-vascular toxicity. Large clinical studies will likely confirm a clinical benefit of proton therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identifying involvement of Lys251/Asp252 pair in electron transfer and associated proton transfer at the quinone reduction site of Rhodobacter capsulatus cytochrome bc1.

PubMed

Kuleta, Patryk; Sarewicz, Marcin; Postila, Pekka; Róg, Tomasz; Osyczka, Artur

2016-10-01

Describing dynamics of proton transfers in proteins is challenging, but crucial for understanding processes which use them for biological functions. In cytochrome bc1, one of the key enzymes of respiration or photosynthesis, proton transfers engage in oxidation of quinol (QH2) and reduction of quinone (Q) taking place at two distinct catalytic sites. Here we evaluated by site-directed mutagenesis the contribution of Lys251/Asp252 pair (bacterial numbering) in electron transfers and associated with it proton uptake to the quinone reduction site (Qi site). We showed that the absence of protonable group at position 251 or 252 significantly changes the equilibrium levels of electronic reactions including the Qi-site mediated oxidation of heme bH, reverse reduction of heme bH by quinol and heme bH/Qi semiquinone equilibrium. This implicates the role of H-bonding network in binding of quinone/semiquinone and defining thermodynamic properties of Q/SQ/QH2 triad. The Lys251/Asp252 proton path is disabled only when both protonable groups are removed. With just one protonable residue from this pair, the entrance of protons to the catalytic site is sustained, albeit at lower rates, indicating that protons can travel through parallel routes, possibly involving water molecules. This shows that proton paths display engineering tolerance for change as long as all the elements available for functional cooperation secure efficient proton delivery to the catalytic site. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Proton Beam Therapy

NASA Astrophysics Data System (ADS)

Paganetti, Harald

2017-01-01

Cancer therapy is a multi-modality approach including surgery, systemic or targeted chemotherapy, radiation (external beam or radionuclide), and immunotherapy. Radiation is typically administered using external beam photon therapy. Proton therapy has been around for more than 60 years but was restricted to research laboratories until the 1990s. Since then clinical proton therapy has been growing rapidly with currently more than 50 facilities worldwide. The interest in proton therapy stems from the physical properties of protons allowing for advanced dose sculpting around the target and sparing of healthy tissue. This review first evaluates the basics of proton therapy physics and technology and then outlines some of the current physical, biological, and clinical challenges. Solving these will ultimately determine whether proton therapy will continue on its path to becoming mainstream.

Shock Acceleration of Solar Energetic Protons: The First 10 Minutes

NASA Technical Reports Server (NTRS)

Ng, Chee K.; Reames, Donald V.

2008-01-01

Proton acceleration at a parallel coronal shock is modeled with self-consistent Alfven wave excitation and shock transmission. 18 - 50 keV seed protons at 0.1% of plasma proton density are accelerated in 10 minutes to a power-law intensity spectrum rolling over at 300 MeV by a 2500km s-1 shock traveling outward from 3.5 solar radius, for typical coronal conditions and low ambient wave intensities. Interaction of high-energy protons of large pitch-angles with Alfven waves amplified by low-energy protons of small pitch angles is key to rapid acceleration. Shock acceleration is not significantly retarded by sunward streaming protons interacting with downstream waves. There is no significant second-order Fermi acceleration.

Release from ISOLDE molten metal targets under pulsed proton beam conditions

NASA Astrophysics Data System (ADS)

Lettry, J.; Catherall, R.; Cyvoct, G.; Evensen, A. H. M.; Lindroos, M.; Jonsson, O. C.; Kugler, E.; Schindl, K.; Ravn, H.; Wildner, E.; Drumm, P.; Obert, J.; Putaux, J. C.; Sauvage, J.

1996-04-01

By moving the ISOLDE mass separators from the 600 MeV Synchrocyclotron (SC) to the 1 GeV Proton-Synchrotron-Booster (PS) the instantaneous energy density of the proton beam went up by 3 orders of magnitude. The developments of the molten metal target units and the optimization of the PS proton beam to cope with the effects of the thermal shocks induced by the proton beam are described. The energy density of the PS proton beam was reduced by spatial defocusing and time staggered extraction of the four PS-accelerators. The release from lanthanum, lead and tin targets is discussed for different settings of the proton beam and compared to the release observed at ISOLDE-SC. The yields of Hg isotopes are presented.

Metabolomics by proton nuclear magnetic resonance spectroscopy of the response to chloroethylnitrosourea reveals drug efficacy and tumor adaptive metabolic pathways.

PubMed

Morvan, Daniel; Demidem, Aicha

2007-03-01

Metabolomics of tumors may allow discovery of tumor biomarkers and metabolic therapeutic targets. Metabolomics by two-dimensional proton high-resolution magic angle spinning nuclear magnetic resonance spectroscopy was applied to investigate metabolite disorders following treatment by chloroethylnitrosourea of murine B16 melanoma (n = 33) and 3LL pulmonary carcinoma (n = 31) in vivo. Treated tumors of both types resumed growth after a delay. Nitrosoureas provoke DNA damage but the metabolic consequences of genotoxic stress are little known yet. Although some differences were observed in the metabolite profile of untreated tumor types, the prominent metabolic features of the response to nitrosourea were common to both. During the growth inhibition phase, there was an accumulation of glucose (more than x10; P < 0.05), glutamine (x3 to 4; P < 0.01), and aspartate (x2 to 5; P < 0.01). This response testified to nucleoside de novo synthesis down-regulation and drug efficacy. However, this phase also involved the increase in alanine (P < 0.001 in B16 melanoma), the decrease in succinate (P < 0.001), and the accumulation of serine-derived metabolites (glycine, phosphoethanolamine, and formate; P < 0.01). This response witnessed the activation of pathways implicated in energy production and resumption of nucleotide de novo synthesis, thus metabolic pathways of DNA repair and adaptation to treatment. During the growth recovery phase, it remained polyunsaturated fatty acid accumulation (x1.5 to 2; P < 0.05) and reduced utilization of glucose compared with glutamine (P < 0.05), a metabolic fingerprint of adaptation. Thus, this study provides the proof of principle that metabolomics of tumor response to an anticancer agent may help discover metabolic pathways of drug efficacy and adaptation to treatment.

Repurposing of Proton Pump Inhibitors as first identified small molecule inhibitors of endo-β-N-acetylglucosaminidase (ENGase) for the treatment of NGLY1 deficiency, a rare genetic disease.

PubMed

Bi, Yiling; Might, Matthew; Vankayalapati, Hariprasad; Kuberan, Balagurunathan

2017-07-01

N-Glycanase deficiency, or NGLY1 deficiency, is an extremely rare human genetic disease. N-Glycanase, encoded by the gene NGLY1, is an important enzyme involved in protein deglycosylation of misfolded proteins. Deglycosylation of misfolded proteins precedes the endoplasmic reticulum (ER)-associated degradation (ERAD) process. NGLY1 patients produce little or no N-glycanase (Ngly1), and the symptoms include global developmental delay, frequent seizures, complex hyperkinetic movement disorder, difficulty in swallowing/aspiration, liver dysfunction, and a lack of tears. Unfortunately, there has not been any therapeutic option available for this rare disease so far. Recently, a proposed molecular mechanism for NGLY1 deficiency suggested that endo-β-N-acetylglucosaminidase (ENGase) inhibitors may be promising therapeutics for NGLY1 patients. Herein, we performed structure-based virtual screening utilizing FDA-approved drug database on this ENGase target to enable repurposing of existing drugs. Several Proton Pump Inhibitors (PPIs), a series of substituted 1H-benzo [d] imidazole, and 1H-imidazo [4,5-b] pyridines, among other scaffolds, have been identified as potent ENGase inhibitors. An electrophoretic mobility shift assay was employed to assess the inhibition of ENGase activity by these PPIs. Our efforts led to the discovery of Rabeprazole Sodium as the most promising hit with an IC 50 of 4.47±0.44μM. This is the first report that describes the discovery of small molecule ENGase inhibitors, which can potentially be used for the treatment of human NGLY1 deficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

G Protein-coupled pH-sensing Receptor OGR1 Is a Regulator of Intestinal Inflammation

PubMed Central

de Vallière, Cheryl; Wang, Yu; Eloranta, Jyrki J.; Vidal, Solange; Clay, Ieuan; Spalinger, Marianne R.; Tcymbarevich, Irina; Terhalle, Anne; Ludwig, Marie-Gabrielle; Suply, Thomas; Fried, Michael; Kullak-Ublick, Gerd A.; Frey-Wagner, Isabelle; Scharl, Michael; Seuwen, Klaus; Wagner, Carsten A.

2015-01-01

Background: A novel family of proton-sensing G protein-coupled receptors, including OGR1, GPR4, and TDAG8, was identified to be important for physiological pH homeostasis and inflammation. Thus, we determined the function of proton-sensing OGR1 in the intestinal mucosa. Mtehods: OGR1 expression in colonic tissues was investigated in controls and patients with IBD. Expression of OGR1 upon cell activation was studied in the Mono Mac 6 (MM6) cell line and primary human and murine monocytes by real-time PCR. Ogr1 knockout mice were crossbred with Il-10 deficient mice and studied for more than 200 days. Microarray profiling was performed using Ogr1−/− and Ogr1+/+ (WT) residential peritoneal macrophages. Results: Patients with IBD expressed higher levels of OGR1 in the mucosa than non-IBD controls. Treatment of MM6 cells with TNF, led to significant upregulation of OGR1 expression, which could be reversed by the presence of NF-κB inhibitors. Kaplan–Meier survival analysis showed a significantly delayed onset and progression of rectal prolapse in female Ogr1−/−/Il-10−/− mice. These mice displayed significantly less rectal prolapses. Upregulation of gene expression, mediated by OGR1, in response to extracellular acidification in mouse macrophages was enriched for inflammation and immune response, actin cytoskeleton, and cell-adhesion gene pathways. Conclusions: OGR1 expression is induced in cells of human macrophage lineage and primary human monocytes by TNF. NF-κB inhibition reverses the induction of OGR1 expression by TNF. OGR1 deficiency protects from spontaneous inflammation in the Il-10 knockout model. Our data indicate a pathophysiological role for pH-sensing receptor OGR1 during the pathogenesis of mucosal inflammation. PMID:25856770

G Protein-coupled pH-sensing Receptor OGR1 Is a Regulator of Intestinal Inflammation.

PubMed

de Vallière, Cheryl; Wang, Yu; Eloranta, Jyrki J; Vidal, Solange; Clay, Ieuan; Spalinger, Marianne R; Tcymbarevich, Irina; Terhalle, Anne; Ludwig, Marie-Gabrielle; Suply, Thomas; Fried, Michael; Kullak-Ublick, Gerd A; Frey-Wagner, Isabelle; Scharl, Michael; Seuwen, Klaus; Wagner, Carsten A; Rogler, Gerhard

2015-06-01

A novel family of proton-sensing G protein-coupled receptors, including OGR1, GPR4, and TDAG8, was identified to be important for physiological pH homeostasis and inflammation. Thus, we determined the function of proton-sensing OGR1 in the intestinal mucosa. OGR1 expression in colonic tissues was investigated in controls and patients with IBD. Expression of OGR1 upon cell activation was studied in the Mono Mac 6 (MM6) cell line and primary human and murine monocytes by real-time PCR. Ogr1 knockout mice were crossbred with Il-10 deficient mice and studied for more than 200 days. Microarray profiling was performed using Ogr1 and Ogr1 (WT) residential peritoneal macrophages. Patients with IBD expressed higher levels of OGR1 in the mucosa than non-IBD controls. Treatment of MM6 cells with TNF, led to significant upregulation of OGR1 expression, which could be reversed by the presence of NF-κB inhibitors. Kaplan-Meier survival analysis showed a significantly delayed onset and progression of rectal prolapse in female Ogr1/Il-10 mice. These mice displayed significantly less rectal prolapses. Upregulation of gene expression, mediated by OGR1, in response to extracellular acidification in mouse macrophages was enriched for inflammation and immune response, actin cytoskeleton, and cell-adhesion gene pathways. OGR1 expression is induced in cells of human macrophage lineage and primary human monocytes by TNF. NF-κB inhibition reverses the induction of OGR1 expression by TNF. OGR1 deficiency protects from spontaneous inflammation in the Il-10 knockout model. Our data indicate a pathophysiological role for pH-sensing receptor OGR1 during the pathogenesis of mucosal inflammation.

Pharmacokinetics and pharmacodynamics of the proton pump inhibitors.

PubMed

Shin, Jai Moo; Kim, Nayoung

2013-01-01

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

The fate of radiation induced giant-nucleated cells of human skin fibroblasts

NASA Astrophysics Data System (ADS)

Almahwasi, A. A.; Jeynes, J. C.; Bradley, D. A.; Regan, P. H.

2017-11-01

Radiation-induced giant-nucleated cells (GCs) have been observed to occur within survivors of irradiated cancerous and within healthy cells, both in vivo and in vitro. The expression of such morphological alterations is associated with genomic instability. This study was designed to investigate the fate of GCs induced in a normal human fibroblast cell line (AG1522) after exposure to 0.2, 1 or 2 Gy of X-ray or proton irradiation. The total of 79 individual AG1522 GCs present at 7, 14 or 21 days after each dose point were analysed from fluorescence microscopy images captured over approximately 120 h. The GCs were identified at the beginning of the observation period for each time point post-irradiation and the area of the cell nucleus was measured (μm2) using a cell-recognition MATLAB code. The results demonstrate that the majority of GCs had undergone a prolonged mitotic arrest, which might be an indication of the survival strategy. The live cell microscopy confirms that a giant-nucleated cell formed 14 days after exposure to 0.2 Gy of proton irradiation was divided into two asymmetrical normal-sized cells. These results suggest that a small fraction of GCs can proliferate and form progeny. Some of GCs had disappeared from the microscopy fields. The rate of their loss was decreased as the dose increased but there remains the potential for them to have progeny that could continue to proliferate, ultimately contributing to development of cancer risk. This important method to access delayed effects in normal tissues could act as a potential radioprotective assay for a dose-limiting parameter when applying radiotherapy. These results might have important implications in evaluating risk estimates for patients during radiation therapy treatment.

Proton Beam Therapy Versus Conformal Photon Radiation Therapy for Childhood Craniopharyngioma: Multi-institutional Analysis of Outcomes, Cyst Dynamics, and Toxicity

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

Bishop, Andrew J.; Greenfield, Brad; Mahajan, Anita

2014-10-01

Purpose: We compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity. Methods and Materials: We reviewed records from 52 children treated with PBT (n=21) or IMRT (n=31) at 2 institutions from 1996-2012. Endpoints were overall survival (OS), disease control, cyst dynamics, and toxicity. Results: At 59.6 months' median follow-up (PBT 33 mo vs IMRT 106 mo; P<.001), the 3-year outcomes were 96% for OS, 95% for nodular failure-free survival and 76% for cystic failure-free survival. Neither OS nor disease control differed between treatment groups (OS P=.742;more » nodular failure-free survival P=.546; cystic failure-free survival P=.994). During therapy, 40% of patients had cyst growth (20% requiring intervention); immediately after therapy, 17 patients (33%) had cyst growth (transient in 14), more commonly in the IMRT group (42% vs 19% PBT; P=.082); and 27% experienced late cyst growth (32% IMRT, 19% PBT; P=.353), with intervention required in 40%. Toxicity did not differ between groups. On multivariate analysis, cyst growth was related to visual and hypothalamic toxicity (P=.009 and .04, respectively). Patients given radiation as salvage therapy (for recurrence) rather than adjuvant therapy had higher rates of visual and endocrine (P=.017 and .024, respectively) dysfunction. Conclusions: Survival and disease-control outcomes were equivalent for PBT and IMRT. Cyst growth is common, unpredictable, and should be followed during and after therapy, because it contributes to late toxicity. Delaying radiation therapy until recurrence may result in worse visual and endocrine function.« less

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Single-event Effect Report for EPC Series eGaN FETs: Proton Testing for SEE and TNID Effects

NASA Technical Reports Server (NTRS)

Scheick, Leif

2014-01-01

Previous testing of the Enhanced Power Conversion (EPC) eGaN FETs showed sensitivity to destructive single-event effects (SEE) effects to heavy ions. The presence of tungsten plugs in the gate area raises concerns that the device may be vulnerable to SEE from protons. Irradiation of biased and unbiased devices with heavy ion has results in some damage suspected of being due to total non-ionizing dose (TNID). Proton irradiation is a better radiation type to study this effect. This study presents the results of testing device with protons for SEE and TNID. No SEE in the EPC2012 device, the most sensitive device to SEE, were seen with 53 MeV protons at several angles. The devices continued to function after 1.5 Mrad (Si) of proton dose with only a slight shift in parameters. These results suggest that gross TNID will not be a factor in using these devices nor suffer from SEE due to protons. However, the device should be tested at with 500 MeV protons to guarantee to immunity proton SEE.

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

Effect of in-medium nucleon-nucleon cross section on proton-proton momentum correlation in intermediate-energy heavy-ion collisions

NASA Astrophysics Data System (ADS)

Wang, Ting-Ting; Ma, Yu-Gang; Zhang, Chun-Jian; Zhang, Zheng-Qiao

2018-03-01

The proton-proton momentum correlation function from different rapidity regions is systematically investigated for the Au + Au collisions at different impact parameters and different energies from 400 A MeV to 1500 A MeV in the framework of the isospin-dependent quantum molecular dynamics model complemented by the Lednický-Lyuboshitz analytical method. In particular, the in-medium nucleon-nucleon cross-section dependence of the correlation function is brought into focus, while the impact parameter and energy dependence of the momentum correlation function are also explored. The sizes of the emission source are extracted by fitting the momentum correlation functions using the Gaussian source method. We find that the in-medium nucleon-nucleon cross section obviously influences the proton-proton momentum correlation function, which is from the whole-rapidity or projectile or target rapidity region at smaller impact parameters, but there is no effect on the mid-rapidity proton-proton momentum correlation function, which indicates that the emission mechanism differs between projectile or target rapidity and mid-rapidity protons.

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.

CORRECTING FOR INTERPLANETARY SCATTERING IN VELOCITY DISPERSION ANALYSIS OF SOLAR ENERGETIC PARTICLES

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

Laitinen, T.; Dalla, S.; Huttunen-Heikinmaa, K.

2015-06-10

To understand the origin of Solar Energetic Particles (SEPs), we must study their injection time relative to other solar eruption manifestations. Traditionally the injection time is determined using the Velocity Dispersion Analysis (VDA) where a linear fit of the observed event onset times at 1 AU to the inverse velocities of SEPs is used to derive the injection time and path length of the first-arriving particles. VDA does not, however, take into account that the particles that produce a statistically observable onset at 1 AU have scattered in the interplanetary space. We use Monte Carlo test particle simulations of energeticmore » protons to study the effect of particle scattering on the observable SEP event onset above pre-event background, and consequently on VDA results. We find that the VDA results are sensitive to the properties of the pre-event and event particle spectra as well as SEP injection and scattering parameters. In particular, a VDA-obtained path length that is close to the nominal Parker spiral length does not imply that the VDA injection time is correct. We study the delay to the observed onset caused by scattering of the particles and derive a simple estimate for the delay time by using the rate of intensity increase at the SEP onset as a parameter. We apply the correction to a magnetically well-connected SEP event of 2000 June 10, and show it to improve both the path length and injection time estimates, while also increasing the error limits to better reflect the inherent uncertainties of VDA.« less

Lack of modulation of gastric emptying by dietary nitrate in healthy volunteers.

PubMed

Terai, Shiho; Iijima, Katsunori; Asanuma, Kiyotaka; Ara, Nobuyuki; Uno, Kaname; Abe, Yasuhiko; Koike, Tomoyuki; Imatani, Akira; Ohara, Shuichi; Shimosegawa, Tooru

2009-05-01

Nitric oxide produced endogenously in vagal neurons modulates gastrointestinal motor activity as an important non-adrenergic and non-cholinergic neurotransmitter. Other than through endogenous biosynthesis, a high concentration of nitric oxide also occurs by chemical reactions within the stomach in the presence of gastric acid through the entero-salivary re-circulation of dietary nitrate. Although dietary nitrate can be a potential source of nitric oxide in the human stomach, there has been no report on the effect of dietary nitrate on gastric motor function. The aim of this study is to investigate the effect of dietary nitrate on gastric emptying, one of the major parameters for the gastric motor function. Fifteen healthy volunteers underwent a placebo-controlled (310 mg sodium nitrate or placebo), double-blind, crossover trial. Since a sufficient amount of gastric acid is essential for dietary nitrate-derived nitric oxide generation in the stomach, the same protocol was repeated after 1-week treatment with a proton pump inhibitor, rabeprazole. Gastric emptying was evaluated by (13)C-octanoate breath test. The sodium nitrate ingestion did not affect gastric emptying either prior to or during rabeprazole treatment, although rabeprazole treatment itself significantly delayed gastric emptying, being independent of the dietary nitrate load. Confirmation of the delayed gastric emptying with rabeprazole indicates the sensitivity of the breath test employed in the present study. In conclusion, despite the potential nitrogen source of exogenous nitric oxide, the ingestion of 310 mg sodium nitrate, which is equivalent to the average daily intake of Japanese adults, does not affect gastric emptying in healthy volunteers.

Parameterized spectral distributions for meson production in proton-proton collisions

NASA Technical Reports Server (NTRS)

Schneider, John P.; Norbury, John W.; Cucinotta, Francis A.

1995-01-01

Accurate semiempirical parameterizations of the energy-differential cross sections for charged pion and kaon production from proton-proton collisions are presented at energies relevant to cosmic rays. The parameterizations, which depend on both the outgoing meson parallel momentum and the incident proton kinetic energy, are able to be reduced to very simple analytical formulas suitable for cosmic ray transport through spacecraft walls, interstellar space, the atmosphere, and meteorites.

Development of a Multileaf Collimator for Proton Radiotherapy

DTIC Science & Technology

2011-06-01

to treat shallow depths was also simulated and commissioned in Eclipse . In order to calibrate the number of simulated protons per MU, a reference ...beam technology for proton radiotherapy, and the fourth year of the project to develop image guided treatment protocols for proton therapy. This...radiotherapy to proton therapy, and to develop a decision-making algorithm to maximize the efficiency of the facility. This report describes the

From nanochannel-induced proton conduction enhancement to a nanochannel-based fuel cell.

PubMed

Liu, Shaorong; Pu, Qiaosheng; Gao, Lin; Korzeniewski, Carol; Matzke, Carolyn

2005-07-01

The apparent proton conductivity inside a nanochannel can be enhanced by orders of magnitude due to the electric double layer overlap. A nanochannel filled with an acidic solution is thus a micro super proton conductor, and an array of such nanochannels forms an excellent proton conductive membrane. Taking advantage of this effect, a new class of proton exchange membrane is developed for micro fuel cell applications.

Low-Energy Proton Testing Methodology

NASA Technical Reports Server (NTRS)

Pellish, Jonathan A.; Marshall, Paul W.; Heidel, David F.; Schwank, James R.; Shaneyfelt, Marty R.; Xapsos, M.A.; Ladbury, Raymond L.; LaBel, Kenneth A.; Berg, Melanie; Kim, Hak S.;

Proton conduction in metal-organic frameworks and related modularly built porous solids.

PubMed

Yoon, Minyoung; Suh, Kyungwon; Natarajan, Srinivasan; Kim, Kimoon

2013-03-04

Proton-conducting materials are an important component of fuel cells. Development of new types of proton-conducting materials is one of the most important issues in fuel-cell technology. Herein, we present newly developed proton-conducting materials, modularly built porous solids, including coordination polymers (CPs) or metal-organic frameworks (MOFs). The designable and tunable nature of the porous materials allows for fast development in this research field. Design and synthesis of the new types of proton-conducting materials and their unique proton-conduction properties are discussed. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long Term Mortality and Cancer Risk in Irradiated Rhesus Monkeys

DTIC Science & Technology

1989-01-01

Reticuloendothelium Acute leukemia 32.7 M Electron 1.6 15.0 Subcutis (Leg) Fibrosarcoma 40.5 M Proton 55 8.0 Brain Glioblastoma 42.9 M Electron 1.6 15.0...Subcutis (Leg) Fibrosarcoma 54.3 M Proton 55 6.0 Subcutis (Leg) Fibrosarcoma 54.5 M Proton 55 6.0 Brain Glioblastoma 54.8 M Electron 1.6 15.0 Kidney...55 4.0 Brain Glioblastoma 93.5 F Proton 55 6.0 Brain Glioblastoma 99.7 M Proton Mixed 12.0 Subcutis (Leg) Fibrosarcoma 108.1 M Proton 55 6.0 Mucosa

Long Term Mortality and Cancer Risk in Irradiated Rhesus Monkeys

DTIC Science & Technology

1990-05-01

Subcutis (Leg) Fibrosarcoma 108.1 M Proton 55 6.0 Mucosa ( Nasal ) Carcinoma 116.4 M Proton 138 5.0 Muscle Sarcoma 122.6 F X-ray 2 5.38 Subcutis (Elbow...55 6.0 Brain Glioblastoma 17.2 M Proton 400 1.0 Reticuloendothelium Acute leukemia 32.7 M Electron 1.6 15.0 Subcutis (Leg) Fibrosarcoma 40.5 M Proton...55 8.0 Brain Glioblastoma 42.9 M Electron 1.6 15.0 Subcutis (Leg) Fibrosarcoma 54.3 M Proton 55 6.0 Subcutis (Leg) Fibrosarcoma 54.5 M Proton 55 6.0

A scintillator-based online detector for the angularly resolved measurement of laser-accelerated proton spectra.

PubMed

Metzkes, J; Karsch, L; Kraft, S D; Pawelke, J; Richter, C; Schürer, M; Sobiella, M; Stiller, N; Zeil, K; Schramm, U

2012-12-01

In recent years, a new generation of high repetition rate (~10 Hz), high power (~100 TW) laser systems has stimulated intense research on laser-driven sources for fast protons. Considering experimental instrumentation, this development requires online diagnostics for protons to be added to the established offline detection tools such as solid state track detectors or radiochromic films. In this article, we present the design and characterization of a scintillator-based online detector that gives access to the angularly resolved proton distribution along one spatial dimension and resolves 10 different proton energy ranges. Conceived as an online detector for key parameters in laser-proton acceleration, such as the maximum proton energy and the angular distribution, the detector features a spatial resolution of ~1.3 mm and a spectral resolution better than 1.5 MeV for a maximum proton energy above 12 MeV in the current design. Regarding its areas of application, we consider the detector a useful complement to radiochromic films and Thomson parabola spectrometers, capable to give immediate feedback on the experimental performance. The detector was characterized at an electrostatic Van de Graaff tandetron accelerator and tested in a laser-proton acceleration experiment, proving its suitability as a diagnostic device for laser-accelerated protons.

Two-stage acceleration of protons from relativistic laser-solid interaction

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

Liu Jinlu; Sheng, Z. M.; Zheng, J.

2012-12-21

A two-stage proton acceleration scheme using present-day intense lasers and a unique target design is proposed. The target system consists of a hollow cylinder, inside which is a hollow cone, which is followed by the main target with a flat front and dish-like flared rear surface. At the center of the latter is a tapered proton layer, which is surrounded by outer proton layers at an angle to it. In the first acceleration stage, protons in both layers are accelerated by target normal sheath acceleration. The center-layer protons are accelerated forward along the axis and the side protons are acceleratedmore » and focused towards them. As a result, the side-layer protons radially compress as well as axially further accelerate the front part of the accelerating center-layer protons in the second stage, which are also radially confined and guided by the field of the fast electrons surrounding them. Two-dimensional particle-incell simulation shows that a 79fs 8.5 Multiplication-Sign 10{sup 20} W/cm{sup 2} laser pulse can produce a proton bunch with {approx} 267MeV maximum energy and {approx} 9.5% energy spread, which may find many applications, including cancer therapy.« less

A 3T Sodium and Proton Composite Array Breast Coil

PubMed Central

Kaggie, Joshua D.; Hadley, J. Rock; Badal, James; Campbell, John R.; Park, Daniel J.; Parker, Dennis L.; Morrell, Glen; Newbould, Rexford D.; Wood, Ali F.; Bangerter, Neal K.

2013-01-01

Purpose The objective of this study was to determine whether a sodium phased array would improve sodium breast MRI at 3T. The secondary objective was to create acceptable proton images with the sodium phased array in place. Methods A novel composite array for combined proton/sodium 3T breast MRI is compared to a coil with a single proton and sodium channel. The composite array consists of a 7-channel sodium receive array, a larger sodium transmit coil, and a 4-channel proton transceive array. The new composite array design utilizes smaller sodium receive loops than typically used in sodium imaging, uses novel decoupling methods between the receive loops and transmit loops, and uses a novel multi-channel proton transceive coil. The proton transceive coil reduces coupling between proton and sodium elements by intersecting the constituent loops to reduce their mutual inductance. The coil used for comparison consists of a concentric sodium and proton loop with passive decoupling traps. Results The composite array coil demonstrates a 2–5x improvement in SNR for sodium imaging and similar SNR for proton imaging when compared to a simple single-loop dual resonant design. Conclusion The improved SNR of the composite array gives breast sodium images of unprecedented quality in reasonable scan times. PMID:24105740

Selectivity Mechanism of the Voltage-gated Proton Channel, HV1

NASA Astrophysics Data System (ADS)

Dudev, Todor; Musset, Boris; Morgan, Deri; Cherny, Vladimir V.; Smith, Susan M. E.; Mazmanian, Karine; Decoursey, Thomas E.; Lim, Carmay

2015-05-01

Voltage-gated proton channels, HV1, trigger bioluminescence in dinoflagellates, enable calcification in coccolithophores, and play multifarious roles in human health. Because the proton concentration is minuscule, exquisite selectivity for protons over other ions is critical to HV1 function. The selectivity of the open HV1 channel requires an aspartate near an arginine in the selectivity filter (SF), a narrow region that dictates proton selectivity, but the mechanism of proton selectivity is unknown. Here we use a reduced quantum model to elucidate how the Asp-Arg SF selects protons but excludes other ions. Attached to a ring scaffold, the Asp and Arg side chains formed bidentate hydrogen bonds that occlude the pore. Introducing H3O+ protonated the SF, breaking the Asp-Arg linkage and opening the conduction pathway, whereas Na+ or Cl- was trapped by the SF residue of opposite charge, leaving the linkage intact, thus preventing permeation. An Asp-Lys SF behaved like the Asp-Arg one and was experimentally verified to be proton-selective, as predicted. Hence, interacting acidic and basic residues form favorable AspH0-H2O0-Arg+ interactions with hydronium but unfavorable Asp--X-/X+-Arg+ interactions with anions/cations. This proposed mechanism may apply to other proton-selective molecules engaged in bioenergetics, homeostasis, and signaling.

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

Spot size dependence of laser accelerated protons in thin multi-ion foils

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

Liu, Tung-Chang, E-mail: tcliu@umd.edu; Shao, Xi; Liu, Chuan-Sheng

2014-06-15

We present a numerical study of the effect of the laser spot size of a circularly polarized laser beam on the energy of quasi-monoenergetic protons in laser proton acceleration using a thin carbon-hydrogen foil. The used proton acceleration scheme is a combination of laser radiation pressure and shielded Coulomb repulsion due to the carbon ions. We observe that the spot size plays a crucial role in determining the net charge of the electron-shielded carbon ion foil and consequently the efficiency of proton acceleration. Using a laser pulse with fixed input energy and pulse length impinging on a carbon-hydrogen foil, amore » laser beam with smaller spot sizes can generate higher energy but fewer quasi-monoenergetic protons. We studied the scaling of the proton energy with respect to the laser spot size and obtained an optimal spot size for maximum proton energy flux. Using the optimal spot size, we can generate an 80 MeV quasi-monoenergetic proton beam containing more than 10{sup 8} protons using a laser beam with power 250 TW and energy 10 J and a target of thickness 0.15 wavelength and 49 critical density made of 90% carbon and 10% hydrogen.« less

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

A test of Lee's quasi-linear theory of ion acceleration by interplanetary traveling shocks

NASA Technical Reports Server (NTRS)

Kennel, C. F.; Coroniti, F. V.; Scarf, F. L.; Livesey, W. A.; Russell, C. T.; Smith, E. J.

1986-01-01

Lee's (1983) quasi-linear theory of ion acceleration is tested using ISEE-3 measurements of the November 12, 1978 quasi-parallel interplanetary shock. His theory accounts with varying degrees of precision for the energetic proton spatial profiles; the dependence of the spectral index of the power law proton velocity distribution upon the shock compression ratio; the power law dependence of the upstream proton scalelength upon energy; the absolute magnitude of the upstream proton scale length; the behavior of the energetic proton anisotropy upstream and downstream of the shock; the behavior of the alpha-particle proton ratio upstream; the equality of the spatial scale lengths at the shock of the upstream waves and of the protons that resonate with them; and the dependence of the integrated wave energy density upon the proton energy density at the shock. However, the trace magnetic field frequency spectra disagree with his theory in two ways. The part of the spectrum that can resonate with the observed protons via first-order cyclotron resonance is flat, whereas Lee's theory predicts an f exp - 7/4 frequency dependence for the November 12 shock. Higher frequency waves, which could not resonate with the observed upstream protons, increased in amplitude as the shock approached, suggesting that they too were generated by the shock.

[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 .

Inward diffusion and loss of radiation belt protons

NASA Astrophysics Data System (ADS)

Selesnick, R. S.; Baker, D. N.; Jaynes, A. N.; Li, X.; Kanekal, S. G.; Hudson, M. K.; Kress, B. T.

2016-03-01

Radiation belt protons in the kinetic energy range 24 to 76 MeV are being measured by the Relativistic Electron Proton Telescope on each of the two Van Allen Probes. Data have been processed for the purpose of studying variability in the trapped proton intensity during October 2013 to August 2015. For the lower energies (≲32 MeV), equatorial proton intensity near L = 2 showed a steady increase that is consistent with inward diffusion of trapped solar protons, as shown by positive radial gradients in phase space density at fixed values of the first two adiabatic invariants. It is postulated that these protons were trapped with enhanced efficiency during the 7 March 2012 solar proton event. A model that includes radial diffusion, along with known trapped proton source and loss processes, shows that the observed average rate of increase near L = 2 is predicted by the same model diffusion coefficient that is required to form the entire proton radiation belt, down to low L, over an extended (˜103 year) interval. A slower intensity decrease for lower energies near L = 1.5 may also be caused by inward diffusion, though it is faster than predicted by the model. Higher-energy (≳40 MeV) protons near the L = 1.5 intensity maximum are from cosmic ray albedo neutron decay. Their observed intensity is lower than expected by a factor ˜2, but the discrepancy is resolved by adding an unspecified loss process to the model with a mean lifetime ˜120 years.

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.

Special cases for proton beam radiotherapy: re-irradiation, lymphoma, and breast cancer.

PubMed

Plastaras, John P; Berman, Abigail T; Freedman, Gary M

2014-12-01

The dose distributions that can be achieved with protons are usually superior to those of conventional photon external-beam radiation. There are special cases where proton therapy may offer a substantial potential benefit compared to photon treatments where toxicity concerns dominate. Re-irradiation may theoretically be made safer with proton therapy due to lower cumulative lifetime doses to sensitive tissues, such as the spinal cord. Proton therapy has been used in a limited number of patients with rectal, pancreatic, esophageal, and lung cancers. Chordomas and soft tissue sarcomas require particularly high radiation doses, posing additional challenges for re-irradiation. Lymphoma is another special case where proton therapy may be advantageous. Late toxicities from even relatively low radiation doses, including cardiac complications and second cancers, are of concern in lymphoma patients with high cure rates and long life expectancies. Proton therapy has begun to be used for consolidation after chemotherapy in patients with Hodgkin and non-Hodgkin lymphoma. Breast cancer is another emerging area of proton therapy development and use. Proton therapy may offer advantages compared to other techniques in the setting of breast boosts, accelerated partial breast irradiation, and post-mastectomy radiotherapy. In these settings, proton therapy may decrease toxicity associated with breast radiotherapy. As techniques are refined in proton therapy, we may be able to improve the therapeutic ratio by maintaining the benefits of radiotherapy while better minimizing the risks. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Whitaker, Thomas J., E-mail: whitaker.thomas@mayo.edu; Beltran, Chris; Tryggestad, Erik

Purpose: Delayed charge is a small amount of charge that is delivered to the patient after the planned irradiation is halted, which may degrade the quality of the treatment by delivering unwarranted dose to the patient. This study compares two methods for minimizing the effect of delayed charge on the dose delivered with a synchrotron based discrete spot scanning proton beam. Methods: The delivery of several treatment plans was simulated by applying a normally distributed value of delayed charge, with a mean of 0.001(SD 0.00025) MU, to each spot. Two correction methods were used to account for the delayed charge.more » Method one (CM1), which is in active clinical use, accounts for the delayed charge by adjusting the MU of the current spot based on the cumulative MU. Method two (CM2) in addition reduces the planned MU by a predicted value. Every fraction of a treatment was simulated using each method and then recomputed in the treatment planning system. The dose difference between the original plan and the sum of the simulated fractions was evaluated. Both methods were tested in a water phantom with a single beam and simple target geometry. Two separate phantom tests were performed. In one test the dose per fraction was varied from 0.5 to 2 Gy using 25 fractions per plan. In the other test the number fractions were varied from 1 to 25, using 2 Gy per fraction. Three patient plans were used to determine the effect of delayed charge on the delivered dose under realistic clinical conditions. The order of spot delivery using CM1 was investigated by randomly selecting the starting spot for each layer, and by alternating per layer the starting spot from first to last. Only discrete spot scanning was considered in this study. Results: Using the phantom setup and varying the dose per fraction, the maximum dose difference for each plan of 25 fractions was 0.37–0.39 Gy and 0.03–0.05 Gy for CM1 and CM2, respectively. While varying the total number of fractions, the maximum dose difference increased at a rate of 0.015 Gy and 0.0018 Gy per fraction for CM1 and CM2, respectively. For CM1, the largest dose difference was found at the location of the first spot in each energy layer, whereas for CM2 the difference in dose was small and showed no dependence on location. For CM1, all of the fields in the patient plans had an area where their excess dose overlapped. No such correlation was found when using CM2. Randomly selecting the starting spot reduces the maximum dose difference from 0.708 to 0.15 Gy. Alternating between first and last spot reduces the maximum dose difference from 0.708 to 0.37 Gy. In the patient plans the excess dose scaled linearly at 0.014 Gy per field per fraction for CM1 and standard delivery order. Conclusions: The predictive model CM2 is superior to a cumulative irradiation model CM1 for minimizing the effects of delayed charge, particularly when considering maximal dose discrepancies and the potential for unplanned hot-spots. This study shows that the dose discrepancy potentially scales at 0.014 Gy per field per fraction for CM1.« less

Fuel-Cell Electrolytes Based on Organosilica Hybrid Proton Conductors

NASA Technical Reports Server (NTRS)

Narayan, Sri R.; Yen, Shiao-Pin S.

2008-01-01

A new membrane composite material that combines an organosilica proton conductor with perfluorinated Nafion material to achieve good proton conductivity and high-temperature performance for membranes used for fuel cells in stationary, transportation, and portable applications has been developed. To achieve high proton conductivities of the order of 10(exp -1)S/cm over a wide range of temperatures, a composite membrane based on a new class of mesoporous, proton-conducting, hydrogen-bonded organosilica, used with Nafion, will allow for water retention and high proton conductivity over a wider range of temperatures than currently offered by Nafion alone. At the time of this reporting, this innovation is at the concept level. Some of the materials and processes investigated have shown good proton conductivity, but membranes have not yet been prepared and demonstrated.

Neutrinos from the primary proton-proton fusion process in the Sun

NASA Astrophysics Data System (ADS)

BOREXINO Collaboration; Bellini, G.; Benziger, J.; Bick, D.; Bonfini, G.; Bravo, D.; Caccianiga, B.; Cadonati, L.; Calaprice, F.; Caminata, A.; Cavalcante, P.; Chavarria, A.; Chepurnov, A.; D'Angelo, D.; Davini, S.; Derbin, A.; Empl, A.; Etenko, A.; Fomenko, K.; Franco, D.; Gabriele, F.; Galbiati, C.; Gazzana, S.; Ghiano, C.; Giammarchi, M.; Göger-Neff, M.; Goretti, A.; Gromov, M.; Hagner, C.; Hungerford, E.; Ianni, Aldo; Ianni, Andrea; Kobychev, V.; Korablev, D.; Korga, G.; Kryn, D.; Laubenstein, M.; Lehnert, B.; Lewke, T.; Litvinovich, E.; Lombardi, F.; Lombardi, P.; Ludhova, L.; Lukyanchenko, G.; Machulin, I.; Manecki, S.; Maneschg, W.; Marcocci, S.; Meindl, Q.; Meroni, E.; Meyer, M.; Miramonti, L.; Misiaszek, M.; Montuschi, M.; Mosteiro, P.; Muratova, V.; Oberauer, L.; Obolensky, M.; Ortica, F.; Otis, K.; Pallavicini, M.; Papp, L.; Perasso, L.; Pocar, A.; Ranucci, G.; Razeto, A.; Re, A.; Romani, A.; Rossi, N.; Saldanha, R.; Salvo, C.; Schönert, S.; Simgen, H.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Sukhotin, S.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Vignaud, D.; Vogelaar, R. B.; von Feilitzsch, F.; Wang, H.; Winter, J.; Wojcik, M.; Wright, A.; Wurm, M.; Zaimidoroga, O.; Zavatarelli, S.; Zuber, K.; Zuzel, G.

2014-08-01

In the core of the Sun, energy is released through sequences of nuclear reactions that convert hydrogen into helium. The primary reaction is thought to be the fusion of two protons with the emission of a low-energy neutrino. These so-called pp neutrinos constitute nearly the entirety of the solar neutrino flux, vastly outnumbering those emitted in the reactions that follow. Although solar neutrinos from secondary processes have been observed, proving the nuclear origin of the Sun's energy and contributing to the discovery of neutrino oscillations, those from proton-proton fusion have hitherto eluded direct detection. Here we report spectral observations of pp neutrinos, demonstrating that about 99 per cent of the power of the Sun, 3.84 × 1033 ergs per second, is generated by the proton-proton fusion process.

The clinical case for proton beam therapy

PubMed Central

2012-01-01

Abstract Over the past 20 years, several proton beam treatment programs have been implemented throughout the United States. Increasingly, the number of new programs under development is growing. Proton beam therapy has the potential for improving tumor control and survival through dose escalation. It also has potential for reducing harm to normal organs through dose reduction. However, proton beam therapy is more costly than conventional x-ray therapy. This increased cost may be offset by improved function, improved quality of life, and reduced costs related to treating the late effects of therapy. Clinical research opportunities are abundant to determine which patients will gain the most benefit from proton beam therapy. We review the clinical case for proton beam therapy. Summary sentence Proton beam therapy is a technically advanced and promising form of radiation therapy. PMID:23083010

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.

Energetic solar proton vs terrestrially trapped proton fluxes. [geocentric space missions shielding requirements

NASA Technical Reports Server (NTRS)

King, J. H.; Stassinopoulos, E. G.

1975-01-01

The relative importance of solar and trapped proton fluxes in the consideration of shielding requirements for geocentric space missions is analyzed. Using models of these particles, their fluences encountered by spacecraft in circular orbits are computed as functions of orbital altitude and inclination, mission duration, threshold energy (10 to 100 MeV), and risk factor (for solar protons only), and ratios of solar-to-trapped fluences are derived. It is shown that solar protons predominate for low-altitude polar and very high-altitude missions, while trapped protons predominate for missions at low and medium altitudes and low inclinations. It is recommended that if the ratio of solar-to-trapped protons falls between 0.1 and 10, both fluences should be considered in planning shielding systems.

The forward rainbow scattering of low energy protons by a graphene sheet

NASA Astrophysics Data System (ADS)

Ćosić, M.; Petrović, S.; Nešković, N.

2018-05-01

This article studies the rainbow scattering of 5-keV protons by the single sheet of free-standing graphene and its possible use as a tool for investigation of the ion-graphene interaction. The proton-graphene interaction potential was constructed by using the Doyle-Turner, ZBL, and Molière proton-carbon interaction potentials. The thermal motion of carbon atoms was included by averaging the potentials according to the Debye model. Proton trajectories were obtained by numerical solution of the corresponding Newton equations of motion. They were used to obtain the mapping of the proton initial positions to their scattering angles. Morphological properties of the introduced mapping including its multiplicity and the rainbow singularities were used to explain important features of the obtained angular distributions of transmitted protons.

Accelerating gradient improvement from hole-boring to light-sail stage using shape-tailored laser front

NASA Astrophysics Data System (ADS)

Wang, W. P.; Shen, B. F.; Xu, Z. Z.

2017-01-01

The accelerating gradient of a proton beam is a crucial factor for the stable radiation pressure acceleration, because quickly accelerating protons into the relativistic region may reduce the multidimensional instability grow to a certain extent. In this letter, a shape-tailored laser is designed to accelerate the protons in a controllable high accelerating gradient in theory. Finally, a proton beam in the gigaelectronvolt range with an energy spread of ˜2.4% is obtained in one-dimensional particle-in-cell simulations. With the future development of the high-intense laser, the ability to accelerate a high energy proton beam using a shape-tailored laser will be important for realistic proton applications, such as fast ignition for inertial confinement fusion, medical therapy, and proton imaging.

New Strategies in Radiation Therapy: Exploiting the Full Potential of Protons

PubMed Central

Mohan, Radhe; Mahajan, Anita; Minsky, Bruce D.

2013-01-01

Protons provide significant dosimetric advantages compared with photons due to their unique depth-dose distribution characteristics. However, they are more sensitive to the effects of intra- and inter-treatment fraction anatomic variations and uncertainties in treatment setup. Furthermore, in the current practice of proton therapy, the biological effectiveness of protons relative to photons is assumed to have a generic fixed value of 1.1. However, this is a simplification, and it is likely higher in different portions of the proton beam. Current clinical practice and trials have not fully exploited the unique physical and biological properties of protons. Intensity-modulated proton therapy, with its ability to manipulate energies (in addition to intensities), provides an entirely new dimension, which, with ongoing research, has considerable potential to increase the therapeutic ratio. PMID:24077353

New strategies in radiation therapy: exploiting the full potential of protons.

PubMed

Mohan, Radhe; Mahajan, Anita; Minsky, Bruce D

2013-12-01

Protons provide significant dosimetric advantages compared with photons because of their unique depth-dose distribution characteristics. However, they are more sensitive to the effects of intra- and intertreatment fraction anatomic variations and uncertainties in treatment setup. Furthermore, in the current practice of proton therapy, the biologic effectiveness of protons relative to photons is assumed to have a generic fixed value of 1.1. However, this is a simplification, and it is likely higher in different portions of the proton beam. Current clinical practice and trials have not fully exploited the unique physical and biologic properties of protons. Intensity-modulated proton therapy, with its ability to manipulate energies (in addition to intensities), provides an entirely new dimension, which, with ongoing research, has considerable potential to increase the therapeutic ratio. ©2013 AACR.

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

Lujano, C; Hernandez, N; Keith, T

Purpose: To describe the proton phantoms that IROC Houston uses to approve and credential proton institutions to participate in NCI-sponsored clinical trials. Methods: Photon phantoms cannot necessarily be used for proton measurements because protons react differently than photons in some plastics. As such plastics that are tissue equivalent for protons were identified. Another required alteration is to ensure that the film dosimeters are housed in the phantom with no air gap to avoid proton streaming. Proton-equivalent plastics/materials used include RMI Solid Water, Techron HPV, blue water, RANDO soft tissue material, balsa wood, compressed cork and polyethylene. Institutions wishing to bemore » approved or credentialed request a phantom and are prioritized for delivery. At the institution, the phantom is imaged, a treatment plan is developed, positioned on the treatment couch and the treatment is delivered. The phantom is returned and the measured dose distributions are compared to the institution’s electronically submitted treatment plan dosimetry data. Results: IROC Houston has developed an extensive proton phantom approval/credentialing program consisting of five different phantoms designs: head, prostate, lung, liver and spine. The phantoms are made with proton equivalent plastics that have HU and relative stopping powers similar (within 5%) of human tissues. They also have imageable targets, avoidance structures, and heterogeneities. TLD and radiochromic film are contained in the target structures. There have been 13 head, 33 prostate, 18 lung, 2 liver and 16 spine irradiations with either passive scatter, or scanned proton beams. The pass rates have been: 100%, 69.7%, 72.2%, 50%, and 81.3%, respectively. Conclusion: IROC Houston has responded to the recent surge in proton facilities by developing a family of anthropomorphic phantoms that are able to be used for remote audits of proton beams. Work supported by PHS grant CA10953 and CA081647.« less

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

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

Cliver, E. W.

2016-12-01

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

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

NASA Astrophysics Data System (ADS)

Cliver, E. W.

2016-12-01

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

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.

New Measurements of Inner Belt Proton Flux Gradients From the Van Allen Probes Mission

NASA Astrophysics Data System (ADS)

Mazur, J. E.; O'Brien, T. P.; Looper, M. D.; George, J. S.; Blake, J. B.

2013-12-01

Prior studies of 10's of MeV inner belt protons in low Earth orbit have established that the atmospheric density gradient produces a proton flux gradient because of losses to the atmosphere and the comparable sizes of the proton qyroradius and atmosphere scale height. The observable is an east-west asymmetry in the proton flux that has been reported using many low-Earth orbit missions going back to the first nuclear emulsion flights in 1963. We will revisit this low-altitude east-west effect as well as higher-altitude gradients with new measurements from the Relativistic Proton Spectrometer (RPS) on the Van Allen Probes spacecraft. RPS is a particle spectrometer designed to measure the flux, angular distribution, and energy spectrum of protons from ~60 MeV to ~2000 MeV with good rejection of penetrating backgrounds by requiring a 10-fold coincidence in its stack of silicon detectors. The Van Allen Probes orbit allows for a survey of proton gradients not only at low altitudes but also as high as the outer trapping limit at McIlwain L shell L~3 corresponding to ~13,000 km altitude. The 60 MeV proton gyroradius varies from ~50 to 700 km in this altitude range. The 1-second sampling of RPS and the nominal 5 rpm rotation rate of the Van Allen Probes yields a sensitive measure of proton gradients. This is the first time that a single mission can address the gradients and trapping of high-energy protons throughout the inner belt. We will report on preliminary flux gradients of >61 MeV protons observed during the first year of the mission using RPS and ancillary geophysical data.

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

Proton dose distribution measurements using a MOSFET detector with a simple dose-weighted correction method for LET effects.

PubMed

Kohno, Ryosuke; Hotta, Kenji; Matsuura, Taeko; Matsubara, Kana; Nishioka, Shie; Nishio, Teiji; Kawashima, Mitsuhiko; Ogino, Takashi

2011-04-04

We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth-dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high-bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L-shaped bolus. The dose reproducibility, angular dependence and depth-dose response were evaluated using a 190 MeV proton beam. Depth-output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose-weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L-shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors.

Proton dose distribution measurements using a MOSFET detector with a simple dose‐weighted correction method for LET effects

PubMed Central

Hotta, Kenji; Matsuura, Taeko; Matsubara, Kana; Nishioka, Shie; Nishio, Teiji; Kawashima, Mitsuhiko; Ogino, Takashi

2011-01-01

We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth‐dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high‐bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L‐shaped bolus. The dose reproducibility, angular dependence and depth‐dose response were evaluated using a 190 MeV proton beam. Depth‐output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose‐weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L‐shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors. PACS number: 87.56.‐v

Proton and hydrogen transport through two-dimensional monolayers

NASA Astrophysics Data System (ADS)

Seel, Max; Pandey, Ravindra

2016-06-01

Diffusion of protons and hydrogen atoms in representative two-dimensional materials is investigated. Specifically, density functional calculations were performed on graphene, hexagonal boron nitride (h-BN), phosphorene, silicene, and molybdenum disulfide (MoS2) monolayers to study the surface interaction and penetration barriers for protons and hydrogen atoms employing finite cluster models. The calculated barrier heights correlate approximately with the size of the opening formed by the three-fold open sites in the monolayers considered. They range from 1.56 eV (proton) and 4.61 eV (H) for graphene to 0.12 eV (proton) and 0.20 eV (H) for silicene. The results indicate that only graphene and h-BN monolayers have the potential for membranes with high selective permeability. The MoS2 monolayer behaves differently: protons and H atoms become trapped between the outer S layers in the Mo plane in a well with a depth of 1.56 eV (proton) and 1.5 eV (H atom), possibly explaining why no proton transport was detected, suggesting MoS2 as a hydrogen storage material instead. For graphene and h-BN, off-center proton penetration reduces the barrier to 1.38 eV for graphene and 0.11 eV for h-BN. Furthermore, Pt acting as a substrate was found to have a negligible effect on the barrier height. In defective graphene, the smallest barrier for proton diffusion (1.05 eV) is found for an oxygen-terminated defect. Therefore, it seems more likely that thermal protons can penetrate a monolayer of h-BN but not graphene and defects are necessary to facilitate the proton transport in graphene.

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.

Copper-Containing Nitrite Reductase Employing Proton-Coupled Spin-Exchanged Electron-Transfer and Multiproton Synchronized Transfer to Reduce Nitrite.

PubMed

Qin, Xin; Deng, Li; Hu, Caihong; Li, Li; Chen, Xiaohua

2017-10-20

The possible catalytic mechanism of the reduction of nitrite by copper-containing nitrite reductases (CuNiRs) is examined by using the M06 function according to two copper models, which include type-one copper (T1Cu) and type-two copper (T2Cu) sites. Examinations confirm that the protonation of two residues, His255 and Asp98, near the T2Cu site, can modulate the redox states of T1Cu and T2Cu, but cannot directly cause electron transfer from T1Cu to T2Cu. The electron hole remains at the T2Cu site when only one residue, His255 or Asp98, is protonated. However, the hole resides at the T1Cu site when both His255 and Asp98 are protonated. Then, the first protonation of nitrite takes place through indirect proton transfer from protonated His255 through the bridging H 2 O and Asp98 with three protons moving together, which cannot cause the cleavage of the HO-NO bond. Subsequently, the substrate is required to obtain another proton from reprotonated His255 through the bridging H 2 O. The reprotonation of nitrite induces the generation of nitric oxide (NO) and H 2 O at the T2Cu site through a special double-proton-coupled spin-exchanged electron-transfer mechanism with indirect proton transfer from His255 to the substrate, a beta-electron of T2Cu I shift to the NO cation, and the remaining alpha-electron changing spin direction at the same time. These results may provide useful information to better understand detailed proton-/electron-transfer reactions for the catalytic processes of CuNiR. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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

PubMed

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

2014-11-04

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

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

PubMed Central

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

2014-01-01

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

Monte Carlo simulations of a low energy proton beamline for radiobiological experiments.

PubMed

Dahle, Tordis J; Rykkelid, Anne Marit; Stokkevåg, Camilla H; Mairani, Andrea; Görgen, Andreas; Edin, Nina J; Rørvik, Eivind; Fjæra, Lars Fredrik; Malinen, Eirik; Ytre-Hauge, Kristian S

2017-06-01

In order to determine the relative biological effectiveness (RBE) of protons with high accuracy, radiobiological experiments with detailed knowledge of the linear energy transfer (LET) are needed. Cell survival data from high LET protons are sparse and experiments with low energy protons to achieve high LET values are therefore required. The aim of this study was to quantify LET distributions from a low energy proton beam by using Monte Carlo (MC) simulations, and to further compare to a proton beam representing a typical minimum energy available at clinical facilities. A Markus ionization chamber and Gafchromic films were employed in dose measurements in the proton beam at Oslo Cyclotron Laboratory. Dose profiles were also calculated using the FLUKA MC code, with the MC beam parameters optimized based on comparisons with the measurements. LET spectra and dose-averaged LET (LET d ) were then estimated in FLUKA, and compared with LET calculated from an 80 MeV proton beam. The initial proton energy was determined to be 15.5 MeV, with a Gaussian energy distribution of 0.2% full width at half maximum (FWHM) and a Gaussian lateral spread of 2 mm FWHM. The LET d increased with depth, from approximately 5 keV/μm in the entrance to approximately 40 keV/μm in the distal dose fall-off. The LET d values were considerably higher and the LET spectra were much narrower than the corresponding spectra from the 80 MeV beam. MC simulations accurately modeled the dose distribution from the proton beam and could be used to estimate the LET at any position in the setup. The setup can be used to study the RBE for protons at high LET d , which is not achievable in clinical proton therapy facilities.

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

PubMed

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

2016-11-01

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

Hydrogen-Bonded Network and Water Dynamics in the D-channel of Cytochrome c Oxidase.

PubMed

Ghane, Tahereh; Gorriz, Rene F; Wrzalek, Sandro; Volkenandt, Senta; Dalatieh, Ferand; Reidelbach, Marco; Imhof, Petra

2018-02-12

Proton transfer in cytochrome c oxidase (CcO) from the cellular inside to the binuclear redox centre as well as proton pumping through the membrane takes place through proton entrance via two distinct pathways, the D- and K-channel. Both channels show a dependence of their hydration level on the protonation states of their key residues, K362 for the K-channel, and E286 or D132 for the D-channel. In the oxidative half of CcO's catalytic cycle the D-channel is the proton-conducting path. For this channel, an interplay of protonation state of the D-channel residues with the water and hydrogen-bond dynamics has been observed in molecular dynamics simulations of the CcO protein, embedded in a lipid bi-layer, modelled in different protonation states. Protonation of residue E286 at the end of the D-channel results in a hydrogen-bonded network pointing from E286 to N139, that is against proton transport, and favouring N139 conformations which correspond to a closed asparagine gate (formed by residues N121 and N139). Consequently, the hydration level is lower than with unprotonated E286. In those models, the Asn gate is predominantly open, allowing water molecules to pass and thus increase the hydration level. The hydrogen-bonded network in these states exhibits longer life times of the Asn residues with water than other models and shows the D-channel to be traversable from the entrance, D132, to exit, E286. The D-channel can thus be regarded as auto-regulated with respect to proton transport, allowing proton passage only when required, that is the proton is located at the lower part of the D-channel (D132 to Asn gate) and not at the exit (E286).

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.

PREFACE: Transport phenomena in proton conducting media Transport phenomena in proton conducting media

NASA Astrophysics Data System (ADS)

Eikerling, Michael

2011-06-01

Proton transport phenomena are of paramount importance for acid-base chemistry, energy transduction in biological organisms, corrosion processes, and energy conversion in electrochemical systems such as polymer electrolyte fuel cells. The relevance for such a plethora of materials and systems, and the ever-lasting fascination with the highly concerted nature of underlying processes drive research across disciplines in chemistry, biology, physics and chemical engineering. A proton never travels alone. Proton motion is strongly correlated with its environment, usually comprised of an electrolyte and a solid or soft host material. For the transport in nature's most benign proton solvent and shuttle, water that is, insights from ab initio simulations, matured over the last 15 years, have furnished molecular details of the structural diffusion mechanism of protons. Excess proton movement in water consists of sequences of Eigen-Zundel-Eigen transitions, triggered by hydrogen bond breaking and making in the surrounding water network. Nowadays, there is little debate about the validity of this mechanism in water, which bears a stunning resemblance to the basic mechanistic picture put forward by de Grotthuss in 1806. While strong coupling of an excess proton with degrees of freedom of solvent and host materials facilitates proton motion, this coupling also creates negative synergies. In general, proton mobility in biomaterials and electrochemical proton conducting media is highly sensitive to the abundance and structure of the proton solvent. In polymer electrolyte membranes, in which protons are bound to move in nano-sized water-channels, evaporation of water or local membrane dehydration due to electro-osmotic coupling are well-known phenomena that could dramatically diminish proton conductivity. Contributions in this special issue address various vital aspects of the concerted nature of proton motion and they elucidate important structural and dynamic effects of solvent, charge-bearing species at interfaces and porous host materials on proton transport properties. As a common thread, articles in this special issue contribute to understanding the functionality provided by complex materials, beyond hydrogen bond fluctuations in water. The first group of articles (Smirnov et al, Henry et al, Medvedev and Stuchebrukhov) elucidates various aspects of the impact of local structural fluctuations, hydrogen bonding and long-range electrostatic forces on proton transfer across and at the surface of mitochondrial membranes. The second group of articles (Ilhan and Spohr, Allahyarov et al and Idupulapati et al) employ molecular dynamics simulations to rationalize vital dependencies of proton transport mechanisms in aqueous-based polymer electrolyte membranes on the nanoporous, phase-separated ionomer morphology, and on the level of hydration. The articles by Gebel et al, Boillat et al, and Aleksandrova et al employ small angle neutron scattering, neutron radiography, and electrochemical atomic force microscopy, respectively, to obtain detailed insights into the kinetics of water sorption, water distribution, water transport properties, as well as spatial maps of proton conductivity in fuel cell membranes. The contribution of Paschos et al provides a comprehensive review of phosphate-based solid state protonic conductors for intermediate temperature fuel cells. The topic of proton conductive materials for high-temperature, water-free operation of fuel cells is continued in the article of Verbraeken et al which addresses synthesis and characterization of a proton conducting perovskite. The guest editor wishes to acknowledge and thank all contributing authors for their commitment to this special issue. Moreover, I would like to thank the staff at IOP Publishing for coordinating submission and refereeing processes. Finally, for the readers, I hope that this special issue will be a valuable and stimulating source of insights into the versatile and eminently important field of transport phenomena in proton conducting media. Complex dynamics of fluids in disordered and crowded environments contents Electrostatic models of electron-driven proton transfer across a lipid membrane Anatoly Yu Smirnov, Lev G Mourokh and Franco Nori Molecular basis of proton uptake in single and double mutants of cytochrome c oxidase Rowan M Henry, David Caplan, Elisa Fadda and Régis Pomès Proton diffusion along biological membranes E S Medvedev and A A Stuchebrukhov Ab initio molecular dynamics of proton networks in narrow polymer electrolyte pores Mehmet A Ilhan and Eckhard Spohr A simulation study of field-induced proton-conduction pathways in dry ionomers Elshad Allahyarov, Philip L Taylor and Hartmut Löwen Molecular structure and transport dynamics in perfluoro sulfonyl imide membranes Nagesh Idupulapati, Ram Devanathan and Michel Dupuis The kinetics of water sorption in Nafion membranes: a small-angle neutron scattering study Gérard Gebel, Sandrine Lyonnard, Hakima Mendil-Jakani and Arnaud Morin Using 2H labeling with neutron radiography for the study of solid polymer electrolyte water transport properties P Boillat, P Oberholzer, B C Seyfang, A Kästner, R Perego, G G Scherer, E H Lehmann and A Wokaun Spatial distribution and dynamics of proton conductivity in fuel cell membranes: potential and limitations of electrochemical atomic force microscopy measurements E Aleksandrova, S Hink, R Hiesgen and E Roduner A review on phosphate based, solid state, protonic conductors for intermediate temperature fuel cells O Paschos, J Kunze, U Stimming and F Maglia A structural study of the proton conducting B-site ordered perovskite Ba3Ca1.18Ta1.82O8.73 Maarten C Verbraeken, Hermenegildo A L Viana, Philip Wormald and John T S Irvine

Enantioselective Protonation

PubMed Central

Mohr, Justin T.; Hong, Allen Y.; Stoltz, Brian M.

2010-01-01

Enantioselective protonation is a common process in biosynthetic sequences. The decarboxylase and esterase enzymes that effect this valuable transformation are able to control both the steric environment around the proton acceptor (typically an enolate) and the proton donor (typically a thiol). Recently, several chemical methods to achieve enantioselective protonation have been developed by exploiting various means of enantiocontrol in different mechanisms. These laboratory transformations have proven useful for the preparation of a number of valuable organic compounds. PMID:20428461

Electromagnetic structure of the proton within the CP-violation hypothesis

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

Krutov, A. F., E-mail: krutov@ssu.samara.ru; Kudinov, M. Yu., E-mail: kudinov@ssu.samara.ru

2013-11-15

The so-called non-Rosenbluth behavior of the proton electromagnetic form factors can be explained within the hypothesis of CP violation in electromagnetic processes involving composite systems of strongly interacting particles. It is shown that this hypothesis leads to the appearance of an additional, anapole, form factor of the proton. The proton electromagnetic form factors, including the anapole form factor, are estimated on the basis of experimental data on elastic electron-proton scattering.

Trapped Proton Environment in Medium-Earth Orbit (2000-2010)

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

Chen, Yue; Friedel, Reinhard Hans; Kippen, Richard Marc

This report describes the method used to derive fluxes of the trapped proton belt along the GPS orbit (i.e., a Medium-Earth Orbit) during 2000 – 2010, a period almost covering a solar cycle. This method utilizes a newly developed empirical proton radiation-belt model, with the model output scaled by GPS in-situ measurements, to generate proton fluxes that cover a wide range of energies (50keV- 6MeV) and keep temporal features as well. The new proton radiation-belt model is developed based upon CEPPAD proton measurements from the Polar mission (1996 – 2007). Comparing to the de-facto standard empirical model of AP8, thismore » model is not only based upon a new data set representative of the proton belt during the same period covered by GPS, but can also provide statistical information of flux values such as worst cases and occurrence percentiles instead of solely the mean values. The comparison shows quite different results from the two models and suggests that the commonly accepted error factor of 2 on the AP8 flux output over-simplifies and thus underestimates variations of the proton belt. Output fluxes from this new model along the GPS orbit are further scaled by the ns41 in-situ data so as to reflect the dynamic nature of protons in the outer radiation belt at geomagnetically active times. Derived daily proton fluxes along the GPS ns41 orbit, whose data files are delivered along with this report, are depicted to illustrate the trapped proton environment in the Medium-Earth Orbit. Uncertainties on those daily proton fluxes from two sources are evaluated: One is from the new proton-belt model that has error factors < ~3; the other is from the in-situ measurements and the error factors could be ~ 5.« less

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

Richter, H.T.; Brown, L.S.; Lanyi, J.K.

Because asp-85 is the acceptor of the retinal Schiff base proton during light-driven proton transport by bacteriorhodopsin, modulation of its pK{sub a} in the photocycle is to be expected. The complex titration of asp-85 in the unphotolyzed protein was suggested to reflect the dependence of this residue on the protonation state of another, unidentified group. from the pH dependencies of the rate constant for the thermal equilibration of retinal isomeric states (dark adaptation) and the deprotonation kinetics of the Schiff base during the photocycle in the E204Q and E204D mutants, we identify the residue as glu-204. The nature of itsmore » interaction with our recent finding that glu-204 is the origin of the proton released to the extracellular surface upon protonation of asp-85 during that transport. We propose, therefore, that the following series of events occur in the photocycle. Protonation of asp-85 in the proton equilibrium with the Schiff base of the photoisomerized retinal results in the dissociation of glu-204 and proton release to the extracellular surface upon protonation of asp-85 during the transport. We propose, therefore, that the following series of events occur in the photocycle. Protonation of asp-85 in the proton equilibrium with the Schiff base shifts toward complete proton transfer. This constitutes the first phase of the reprotonation switch because it excludes asp-85 as a donor in the reprotonation of the Schiff base that follows. The sequential structural changes of the protein that ensue, detected earlier by diffraction, are suggested to facilitate the change of the access of the Schiff base toward the cytoplasmic side at the second phase of the switch, and the lowering the pK{sub a} of asp-96, so as to make it a proton donor, as the third phase. 77 refs., 6 figs.« less

Determination of the quenching correction factors for plastic scintillation detectors in therapeutic high-energy proton beams

PubMed Central

Wang, L L W; Perles, L A; Archambault, L; Sahoo, N; Mirkovic, D; Beddar, S

2013-01-01

The plastic scintillation detectors (PSD) have many advantages over other detectors in small field dosimetry due to its high spatial resolution, excellent water equivalence and instantaneous readout. However, in proton beams, the PSDs will undergo a quenching effect which makes the signal level reduced significantly when the detector is close to Bragg peak where the linear energy transfer (LET) for protons is very high. This study measures the quenching correction factor (QCF) for a PSD in clinical passive-scattering proton beams and investigates the feasibility of using PSDs in depth-dose measurements in proton beams. A polystyrene based PSD (BCF-12, ϕ0.5mm×4mm) was used to measure the depth-dose curves in a water phantom for monoenergetic unmodulated proton beams of nominal energies 100, 180 and 250 MeV. A Markus plane-parallel ion chamber was also used to get the dose distributions for the same proton beams. From these results, the QCF as a function of depth was derived for these proton beams. Next, the LET depth distributions for these proton beams were calculated by using the MCNPX Monte Carlo code, based on the experimentally validated nozzle models for these passive-scattering proton beams. Then the relationship between the QCF and the proton LET could be derived as an empirical formula. Finally, the obtained empirical formula was applied to the PSD measurements to get the corrected depth-dose curves and they were compared to the ion chamber measurements. A linear relationship between QCF and LET, i.e. Birks' formula, was obtained for the proton beams studied. The result is in agreement with the literature. The PSD measurements after the quenching corrections agree with ion chamber measurements within 5%. PSDs are good dosimeters for proton beam measurement if the quenching effect is corrected appropriately. PMID:23128412

Determination of the quenching correction factors for plastic scintillation detectors in therapeutic high-energy proton beams

NASA Astrophysics Data System (ADS)

Wang, L. L. W.; Perles, L. A.; Archambault, L.; Sahoo, N.; Mirkovic, D.; Beddar, S.

2012-12-01

Plastic scintillation detectors (PSDs) have many advantages over other detectors in small field dosimetry due to their high spatial resolution, excellent water equivalence and instantaneous readout. However, in proton beams, the PSDs undergo a quenching effect which makes the signal level reduced significantly when the detector is close to the Bragg peak where the linear energy transfer (LET) for protons is very high. This study measures the quenching correction factor (QCF) for a PSD in clinical passive-scattering proton beams and investigates the feasibility of using PSDs in depth-dose measurements in proton beams. A polystyrene-based PSD (BCF-12, ϕ0.5 mm × 4 mm) was used to measure the depth-dose curves in a water phantom for monoenergetic unmodulated proton beams of nominal energies 100, 180 and 250 MeV. A Markus plane-parallel ion chamber was also used to get the dose distributions for the same proton beams. From these results, the QCF as a function of depth was derived for these proton beams. Next, the LET depth distributions for these proton beams were calculated by using the MCNPX Monte Carlo code, based on the experimentally validated nozzle models for these passive-scattering proton beams. Then the relationship between the QCF and the proton LET could be derived as an empirical formula. Finally, the obtained empirical formula was applied to the PSD measurements to get the corrected depth-dose curves and they were compared to the ion chamber measurements. A linear relationship between the QCF and LET, i.e. Birks' formula, was obtained for the proton beams studied. The result is in agreement with the literature. The PSD measurements after the quenching corrections agree with ion chamber measurements within 5%. PSDs are good dosimeters for proton beam measurement if the quenching effect is corrected appropriately.

Protonation Dynamics on Lipid Nanodiscs: Influence of the Membrane Surface Area and External Buffers.

PubMed

Xu, Lei; Öjemyr, Linda Näsvik; Bergstrand, Jan; Brzezinski, Peter; Widengren, Jerker

2016-05-10

Lipid membrane surfaces can act as proton-collecting antennae, accelerating proton uptake by membrane-bound proton transporters. We investigated this phenomenon in lipid nanodiscs (NDs) at equilibrium on a local scale, analyzing fluorescence fluctuations of individual pH-sensitive fluorophores at the membrane surface by fluorescence correlation spectroscopy (FCS). The protonation rate of the fluorophores was ∼100-fold higher when located at 9- and 12-nm diameter NDs, compared to when in solution, indicating that the proton-collecting antenna effect is maximal already for a membrane area of ∼60 nm(2). Fluorophore-labeled cytochrome c oxidase displayed a similar increase when reconstituted in 12 nm NDs, but not in 9 nm NDs, i.e., an acceleration of the protonation rate at the surface of cytochrome c oxidase is found when the lipid area surrounding the protein is larger than 80 nm(2), but not when below 30 nm(2). We also investigated the effect of external buffers on the fluorophore proton exchange rates at the ND membrane-water interfaces. With increasing buffer concentrations, the proton exchange rates were found to first decrease and then, at millimolar buffer concentrations, to increase. Monte Carlo simulations, based on a simple kinetic model of the proton exchange at the membrane-water interface, and using rate parameter values determined in our FCS experiments, could reconstruct both the observed membrane-size and the external buffer dependence. The FCS data in combination with the simulations indicate that the local proton diffusion coefficient along a membrane is ∼100 times slower than that observed over submillimeter distances by proton-pulse experiments (Ds ∼ 10(-5)cm(2)/s), and support recent theoretical studies showing that proton diffusion along membrane surfaces is time- and length-scale dependent. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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

Iwata, Hiromitsu, E-mail: h-iwa-ncu@nifty.com; Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya; Ogino, Hiroyuki

Purpose: To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons. Methods and Materials: The RBE of passive scattering proton beams at the center of the spread-out Bragg peak (SOBP) was determined from dose-survival curves in 4 cell lines using 6-MV X rays as controls. Survival of 2 cell lines after spot scanning and passive scattering proton irradiation was then compared. Biological effects at the distal end region of the SOBP were also investigated. Themore » OER of passive scattering proton beams and 6 MX X rays were investigated in 2 cell lines. The RBE and OER values were estimated at a 10% cell survival level. The maximum degree of protection of radiation effects by dimethyl sulfoxide was determined to estimate the contribution of the indirect effect against DNA damage. All experiments comparing protons and X rays were made under the same biological conditions. Results: The RBE values of passive scattering proton beams in the 4 cell lines examined were 1.01 to 1.22 (average, 1.14) and were almost identical to those of spot scanning beams. Biological effects increased at the distal end of the SOBP. In the 2 cell lines examined, the OER was 2.74 (95% confidence interval, 2.56-2.80) and 3.08 (2.84-3.11), respectively, for X rays, and 2.39 (2.38-2.43) and 2.72 (2.69-2.75), respectively, for protons (P<.05 for both cells between X rays and protons). The maximum degree of protection was significantly higher for X rays than for proton beams (P<.05). Conclusions: The RBE values of spot scanning and passive scattering proton beams were almost identical. The OER was lower for protons than for X rays. The lower contribution of the indirect effect may partly account for the lower OER of protons.« less

Quantum dynamics in continuum for proton transport—Generalized correlation

NASA Astrophysics Data System (ADS)

Chen, Duan; Wei, Guo-Wei

2012-04-01

As a key process of many biological reactions such as biological energy transduction or human sensory systems, proton transport has attracted much research attention in biological, biophysical, and mathematical fields. A quantum dynamics in continuum framework has been proposed to study proton permeation through membrane proteins in our earlier work and the present work focuses on the generalized correlation of protons with their environment. Being complementary to electrostatic potentials, generalized correlations consist of proton-proton, proton-ion, proton-protein, and proton-water interactions. In our approach, protons are treated as quantum particles while other components of generalized correlations are described classically and in different levels of approximations upon simulation feasibility and difficulty. Specifically, the membrane protein is modeled as a group of discrete atoms, while ion densities are approximated by Boltzmann distributions, and water molecules are represented as a dielectric continuum. These proton-environment interactions are formulated as convolutions between number densities of species and their corresponding interaction kernels, in which parameters are obtained from experimental data. In the present formulation, generalized correlations are important components in the total Hamiltonian of protons, and thus is seamlessly embedded in the multiscale/multiphysics total variational model of the system. It takes care of non-electrostatic interactions, including the finite size effect, the geometry confinement induced channel barriers, dehydration and hydrogen bond effects, etc. The variational principle or the Euler-Lagrange equation is utilized to minimize the total energy functional, which includes the total Hamiltonian of protons, and obtain a new version of generalized Laplace-Beltrami equation, generalized Poisson-Boltzmann equation and generalized Kohn-Sham equation. A set of numerical algorithms, such as the matched interface and boundary method, the Dirichlet to Neumann mapping, Gummel iteration, and Krylov space techniques, is employed to improve the accuracy, efficiency, and robustness of model simulations. Finally, comparisons between the present model predictions and experimental data of current-voltage curves, as well as current-concentration curves of the Gramicidin A channel, verify our new model.

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.

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

TU-FG-BRB-08: Challenges, Limitations and Future Outlook Towards Clinical Translation of Proton Acoustic Range Verification

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

Yousefi, S; Ahmad, M; Xiang, L

Purpose: To report our investigations of proton acoustic imaging, including computer simulations and preliminary experimental studies at clinical facilities. The ultimate achievable accuracy, sensitivity and clinical translation challenges are discussed. Methods: The acoustic pulse due to pressure rise was estimated using finite element model. Since the ionoacoustic pulse is highly dependent on the proton pulse width and energy, multiple pulse widths were studied. Based on the received signal spectrum at piezoelectric ultrasound transducer with consideration of random thermal noise, maximum spatial resolution of the proton-acoustic imaging modality was calculated. The simulation studies defined the design specifications of the system tomore » detect proton acoustic signal from Hitachi and Mevion clinical machines. A 500 KHz hydrophone with 100 dB amplification was set up in a water tank placed in front of the proton nozzle A 40 MHz data acquisition was synchronized by a trigger signal provided by the machine. Results: Given 30–800 mGy dose per pulse at the Bragg peak, the minimum number of protons detectable by the proton acoustic technique was on the order of 10×10^6 per pulse. The broader pulse widths produce signal with lower acoustic frequencies, with 10 µs pulses producing signals with frequency less than 100 kHz. As the proton beam pulse width increases, a higher dose rate is required to measure the acoustic signal. Conclusion: We have established the minimal detection limit for protonacoustic range validation for a variety of pulse parameters. Our study indicated practical proton-acoustic range verification can be feasible with a pulse shorter than 10 µs, 5×10^6 protons/pulse, 50 nA beam current and a highly sensitive ultrasonic transducer. The translational challenges into current clinical machines include proper magnetic shielding of the measurement equipment, providing a clean trigger signal from the proton machine, providing a shorter proton beam pulse and higher dose per pulse.« less

SU-E-J-201: Investigation of MRI Guided Proton Therapy

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

Li, JS

2015-06-15

Purpose: Image-guided radiation therapy has been employed for cancer treatment to improve the tumor localization accuracy. Radiation therapy with proton beams requires more on this accuracy because the proton beam has larger uncertainty and dramatic dose variation along the beam direction. Among all the image modalities, magnetic-resonance image (MRI) is the best for soft tissue delineation and real time motion monitoring. In this work, we investigated the behavior of the proton beam in magnetic field with Monte Carlo simulations. Methods: A proton Monte Carlo platform, TOPAS, was used for this investigation. Dose calculations were performed with this platform in amore » 30cmx30cmx30cm water phantom for both pencil and broad proton beams with different energies (120, 150 and 180MeV) in different magnetic fields (0.5T, 1T and 3T). The isodose distributions, dose profiles in lateral and beam direction were evaluated. The shifts of the Bragg peak in different magnetic fields for different proton energies were compared and the magnetic field effects on the characters of the dose distribution were analyzed. Results: Significant effects of magnetic field have been observed on the proton beam dose distributions, especially for magnetic field of 1T and up. The effects are more significant for higher energy proton beam because higher energy protons travel longer distance in the magnetic field. The Bragg peak shift in the lateral direction is about 38mm for 180MeV and 11mm for 120MeV proton beams in 3T magnetic field. The peak positions are retracted back for 6mm and 2mm, respectively. The effect on the beam penumbra and dose falloff at the distal edge of the Bragg peak is negligible. Conclusion: Though significant magnetic effects on dose distribution have been observed for proton beams, MRI guided proton therapy is feasible because the magnetic effects on dose is predictable and can be considered in patient dose calculation.« less

MO-FG-CAMPUS-JeP1-03: Luminescence Imaging of Water During Proton Beam Irradiation for Range Estimation

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

Yamamoto, S; Komori, M; Toshito, T

Purpose: Since proton therapy has the ability to selectively deliver a dose to a target tumor, the dose distribution should be accurately measured. A precise and efficient method to evaluate the dose distribution is desired. We found that luminescence was emitted from water during proton irradiation and thought this phenomenon could be used for estimating the dose distribution. Methods: For this purpose, we placed water phantoms set on a table with a spot-scanning proton-therapy system, and luminescence images of these phantoms were measured with a high-sensitivity cooled charge coupled device (CCD) camera during proton-beam irradiation. We also conducted the imagingmore » of phantoms of pure-water, fluorescein solution and acrylic block. We made three dimensional images from the projection data. Results: The luminescence images of water phantoms during the proton-beam irradiations showed clear Bragg peaks, and the measured proton ranges from the images were almost the same as those obtained with an ionization chamber. The image of the pure-water phantom also showed almost the same distribution as the tap-water phantom, indicating that the luminescence image was not related to impurities in the water. The luminescence image of fluorescein solution had ∼3 times higher intensity than water, with the same proton range as that of water. The luminescence image of the acrylic phantom had 14.5% shorter proton range than that of water; the proton range in the acrylic phantom was relatively matched with the calculated value. The luminescence images of the tap-water phantom during proton irradiation could be obtained in less than 2 sec. Three dimensional images were successfully obtained which have more quantitative information. Conclusion: Luminescence imaging during proton-beam irradiation has the potential to be a new method for range estimations in proton therapy.« less

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

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.

Socioeconomic factors affect the selection of proton radiation therapy for children.

PubMed

Shen, Colette J; Hu, Chen; Ladra, Matthew M; Narang, Amol K; Pollack, Craig E; Terezakis, Stephanie A

2017-10-15

Proton radiotherapy remains a limited resource despite its clear potential for reducing radiation doses to normal tissues and late effects in children in comparison with photon therapy. This study examined the impact of race and socioeconomic factors on the use of proton therapy in children with solid malignancies. This study evaluated 12,101 children (age ≤ 21 years) in the National Cancer Data Base who had been diagnosed with a solid malignancy between 2004 and 2013 and had received photon- or proton-based radiotherapy. Logistic regression analysis was used to evaluate patient, tumor, and socioeconomic variables affecting treatment with proton radiotherapy versus photon radiotherapy. Eight percent of the patients in the entire cohort received proton radiotherapy, and this proportion increased between 2004 (1.7%) and 2013 (17.5%). Proton therapy was more frequently used in younger patients (age ≤ 10 years; odds ratio [OR], 1.9; 95% confidence interval [CI], 1.6-2.2) and in patients with bone/joint primaries and ependymoma, medulloblastoma, and rhabdomyosarcoma histologies (P < .05). Patients with metastatic disease were less likely to receive proton therapy (OR, 0.4; 95% CI, 0.3-0.6). Patients with private/managed care were more likely than patients with Medicaid or no insurance to receive proton therapy (P < .0001). A higher median household income and educational attainment were also associated with increased proton use (P < .001). Patients treated with proton therapy versus photon therapy were more likely to travel more than 200 miles (13% vs 5%; P < .0001). Socioeconomic factors affect the use of proton radiotherapy in children. Whether this disparity is related to differences in the referral patterns, the knowledge of treatment modalities, or the ability to travel for therapy needs to be further clarified. Improving access to proton therapy in underserved pediatric populations is essential. Cancer 2017;123:4048-56. © 2017 American Cancer Society. © 2017 American Cancer Society.

Comparing the quality of passively-scattered proton and photon tomotherapy plans for brain and head and neck disease sites.

PubMed

Kainz, Kristofer; Firat, Selim; Wilson, J Frank; Schultz, Christopher; Siker, Malika; Wang, Andrew; Olson, Dan; Li, X Allen

2015-03-21

We compare the quality of photon IMRT (helical tomotherapy) with classic proton plans for brain, head and neck tumors, in terms of target dose uniformity and conformity along with organ-at-risk (OAR) sparing. Plans were created for twelve target volumes among eight cases. All patients were originally planned and treated using helical tomotherapy. Proton plans were generated using a passively-scattered beam model with a maximum range of 32 g cm(-2) (225 MeV), range modulation in 0.5 g cm(-2) increments and range compensators with 4.8 mm milling tool diameters. All proton plans were limited to two to four beams. Plan quality was compared using uniformity index (UI), conformation number (CN) and a EUD-based plan quality index (fEUD). For 11 of the 12 targets, UI was improved for the proton plan; on average, UI was 1.05 for protons versus 1.08 for tomotherapy. For 7 of the 12 targets, the tomotherapy plan exhibited more favorable CN. For proximal OARs, the improved dose conformity to the target volume from tomotherapy led to a lower maximum dose. For distal OARs, the maximum dose was much lower for proton plans. For 6 of the 8 cases, near-total avoidance for distal OARs provided by protons leads to improved fEUD. However, if distal OARs are excluded in the fEUD calculation, the proton plans exhibit better fEUD in only 3 of the 8 cases. The distal OAR sparing and target dose uniformity are generally better with passive-scatter proton planning than with photon tomotherapy; proton therapy may be preferred if the clinician deems those attributes critical. However, tomotherapy may serve equally as well as protons for cases where superior target dose conformity from tomotherapy leads to plan quality nearly identical to or better than protons and for cases where distal OAR sparing is not concerning.

Investigation on using high-energy proton beam for total body irradiation (TBI).

PubMed

Zhang, Miao; Qin, Nan; Jia, Xun; Zou, Wei J; Khan, Atif; Yue, Ning J

2016-09-08

This work investigated the possibility of using proton beam for total body irradia-tion (TBI). We hypothesized the broad-slow-rising entrance dose from a monoen-ergetic proton beam can deliver a uniform dose to patient with varied thickness. Comparing to photon-based TBI, it would not require any patient-specific com-pensator or beam spoiler. The hypothesis was first tested by simulating 250 MeV, 275 MeV, and 300 MeV protons irradiating a wedge-shaped water phantom in a paired opposing arrangement using Monte Carlo (MC) method. To allow ± 7.5% dose variation, the maximum water equivalent thickness (WET) of a treatable patient separation was 29 cm for 250 MeV proton, and > 40 cm for 275 MeV and 300 MeV proton. The compared 6 MV photon can only treat patients with up to 15.5 cm water-equivalent separation. In the second step, we simulated the dose deposition from the same beams on a patient's whole-body CT scan. The maximum patient separation in WET was 23 cm. The calculated whole-body dose variations were ± 8.9%, ± 9.0%, ± 9.6%, and ± 14% for 250 MeV proton, 275 MeV proton, 300 MeV proton, and 6 MV photon. At last, we tested the current machine capability to deliver a monoenergetic proton beam with a large uniform field. Experiments were performed on a compact double scattering single-gantry proton system. With its C-shaped gantry design, the source-to-surface distance (SSD) reached 7 m. The measured dose deposition curve had 22 cm relatively flat entrance region. The full width half maximum field size was measured 105 cm. The current scatter filter had to be redesigned to produce a uniform intensity at such treatment distance. In con-clusion, this work demonstrated the possibility of using proton beam for TBI. The current commercially available proton machines would soon be ready for such task. © 2016 The Authors.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-11-11

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

Overtaking collision effects in a cw double-pass proton linac

DOE PAGES

Tao, Yue; Qiang, Ji; Hwang, Kilean

2017-12-22

The recirculating superconducting proton linac has the advantage of reducing the number of cavities in the accelerator and the corresponding construction and operational costs. Beam dynamics simulations were done recently in a double-pass recirculating proton linac using a single proton beam bunch. For continuous wave (cw) operation, the high-energy proton bunch during the second pass through the linac will overtake and collide with the low-energy bunch during the first pass at a number of locations of the linac. These collisions might cause proton bunch emittance growth and beam quality degradation. Here, we study the collisional effects due to Coulomb space-chargemore » forces between the high-energy bunch and the low-energy bunch. Our results suggest that these effects on the proton beam quality would be small and might not cause significant emittance growth or beam blowup through the linac. A 10 mA, 500 MeV cw double-pass proton linac is feasible without using extra hardware for phase synchronization.« less

Effect of Temperature on the Protonation of the TALSPEAK Ligands: Lactic and Diethylenetrinitropentaacetic Acids

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

Tian, Guoxin; Rao, Linfeng

2009-10-20

The protonation reactions of two ligands that play important roles in the TALSPEAK process for the separation of trivalent actinides from lanthanides, lactic acid and diethylenetrinitropentaacetic acid (DTPA), have been studied at variable temperatures. The protonation constants at 10-70 C were determined by titration potentiometry and the protonation enthalpies were determined at 25 C by titration microcalorimetry. The protonation constants remain essentially unchanged (25-70 C) within the experimental uncertainties, indicating that the effect of temperature on the protonation of lactate is insignificant. In contrast, the protonation constants of DTPA (log {beta}H's) generally decrease as the temperature is increased. Results frommore » this study indicate that the effect of temperature on the protonation of DTPA could alter the speciation of metal ions (actinides and lanthanides) in the TALSPEAK system, since lower values of log{beta}H at higher temperatures suggest that the hydrogen ions would compete less strongly with the metal ions for the complexation of DTPA at higher temperatures.« less

Overtaking collision effects in a cw double-pass proton linac

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

Tao, Yue; Qiang, Ji; Hwang, Kilean

The recirculating superconducting proton linac has the advantage of reducing the number of cavities in the accelerator and the corresponding construction and operational costs. Beam dynamics simulations were done recently in a double-pass recirculating proton linac using a single proton beam bunch. For continuous wave (cw) operation, the high-energy proton bunch during the second pass through the linac will overtake and collide with the low-energy bunch during the first pass at a number of locations of the linac. These collisions might cause proton bunch emittance growth and beam quality degradation. Here, we study the collisional effects due to Coulomb space-chargemore » forces between the high-energy bunch and the low-energy bunch. Our results suggest that these effects on the proton beam quality would be small and might not cause significant emittance growth or beam blowup through the linac. A 10 mA, 500 MeV cw double-pass proton linac is feasible without using extra hardware for phase synchronization.« less

Characteristics of Protons Exiting from a Polyethylene Converter Irradiated by Neutrons with Energies between 1 keV and 10 MeV.

PubMed

Nikezic, D; Shahmohammadi Beni, Mehrdad; Krstic, D; Yu, K N

2016-01-01

Monte Carlo method has been used to determine the efficiency for proton production and to study the energy and angular distributions of the generated protons. The ENDF library of cross sections is used to simulate the interactions between the neutrons and the atoms in a polyethylene (PE) layer, while the ranges of protons with different energies in PE are determined using the Stopping and Range of Ions in Matter (SRIM) computer code. The efficiency of proton production increases with the PE layer thickness. However the proton escaping from a certain polyethylene volume is highly dependent on the neutron energy and target thickness, except for a very thin PE layer. The energy and angular distributions of protons are also estimated in the present paper, showing that, for the range of energy and thickness considered, the proton flux escaping is dependent on the PE layer thickness, with the presence of an optimal thickness for a fixed primary neutron energy.

Characteristics of Protons Exiting from a Polyethylene Converter Irradiated by Neutrons with Energies between 1 keV and 10 MeV

PubMed Central

Nikezic, D.; Shahmohammadi Beni, Mehrdad; Krstic, D.; Yu, K. N.

2016-01-01

Monte Carlo method has been used to determine the efficiency for proton production and to study the energy and angular distributions of the generated protons. The ENDF library of cross sections is used to simulate the interactions between the neutrons and the atoms in a polyethylene (PE) layer, while the ranges of protons with different energies in PE are determined using the Stopping and Range of Ions in Matter (SRIM) computer code. The efficiency of proton production increases with the PE layer thickness. However the proton escaping from a certain polyethylene volume is highly dependent on the neutron energy and target thickness, except for a very thin PE layer. The energy and angular distributions of protons are also estimated in the present paper, showing that, for the range of energy and thickness considered, the proton flux escaping is dependent on the PE layer thickness, with the presence of an optimal thickness for a fixed primary neutron energy. PMID:27362656

Treatment planning, optimization, and beam delivery technqiues for intensity modulated proton therapy

NASA Astrophysics Data System (ADS)

Sengbusch, Evan R.

Physical properties of proton interactions in matter give them a theoretical advantage over photons in radiation therapy for cancer treatment, but they are seldom used relative to photons. The primary barriers to wider acceptance of proton therapy are the technical feasibility, size, and price of proton therapy systems. Several aspects of the proton therapy landscape are investigated, and new techniques for treatment planning, optimization, and beam delivery are presented. The results of these investigations suggest a means by which proton therapy can be delivered more efficiently, effectively, and to a much larger proportion of eligible patients. An analysis of the existing proton therapy market was performed. Personal interviews with over 30 radiation oncology leaders were conducted with regard to the current and future use of proton therapy. In addition, global proton therapy market projections are presented. The results of these investigations serve as motivation and guidance for the subsequent development of treatment system designs and treatment planning, optimization, and beam delivery methods. A major factor impacting the size and cost of proton treatment systems is the maximum energy of the accelerator. Historically, 250 MeV has been the accepted value, but there is minimal quantitative evidence in the literature that supports this standard. A retrospective study of 100 patients is presented that quantifies the maximum proton kinetic energy requirements for cancer treatment, and the impact of those results with regard to treatment system size, cost, and neutron production is discussed. This study is subsequently expanded to include 100 cranial stereotactic radiosurgery (SRS) patients, and the results are discussed in the context of a proposed dedicated proton SRS treatment system. Finally, novel proton therapy optimization and delivery techniques are presented. Algorithms are developed that optimize treatment plans over beam angle, spot size, spot spacing, beamlet weight, the number of delivered beamlets, and the number of delivery angles. These methods are evaluated via treatment planning studies including left-sided whole breast irradiation, lung stereotactic body radiotherapy, nasopharyngeal carcinoma, and whole brain radiotherapy with hippocampal avoidance. Improvements in efficiency and efficacy relative to traditional proton therapy and intensity modulated photon radiation therapy are discussed.

Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells.

PubMed

Iwata, Hiromitsu; Ogino, Hiroyuki; Hashimoto, Shingo; Yamada, Maho; Shibata, Hiroki; Yasui, Keisuke; Toshito, Toshiyuki; Omachi, Chihiro; Tatekawa, Kotoha; Manabe, Yoshihiko; Mizoe, Jun-etsu; Shibamoto, Yuta

2016-05-01

To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons. The RBE of passive scattering proton beams at the center of the spread-out Bragg peak (SOBP) was determined from dose-survival curves in 4 cell lines using 6-MV X rays as controls. Survival of 2 cell lines after spot scanning and passive scattering proton irradiation was then compared. Biological effects at the distal end region of the SOBP were also investigated. The OER of passive scattering proton beams and 6 MX X rays were investigated in 2 cell lines. The RBE and OER values were estimated at a 10% cell survival level. The maximum degree of protection of radiation effects by dimethyl sulfoxide was determined to estimate the contribution of the indirect effect against DNA damage. All experiments comparing protons and X rays were made under the same biological conditions. The RBE values of passive scattering proton beams in the 4 cell lines examined were 1.01 to 1.22 (average, 1.14) and were almost identical to those of spot scanning beams. Biological effects increased at the distal end of the SOBP. In the 2 cell lines examined, the OER was 2.74 (95% confidence interval, 2.56-2.80) and 3.08 (2.84-3.11), respectively, for X rays, and 2.39 (2.38-2.43) and 2.72 (2.69-2.75), respectively, for protons (P<.05 for both cells between X rays and protons). The maximum degree of protection was significantly higher for X rays than for proton beams (P<.05). The RBE values of spot scanning and passive scattering proton beams were almost identical. The OER was lower for protons than for X rays. The lower contribution of the indirect effect may partly account for the lower OER of protons. Copyright © 2016 Elsevier Inc. All rights reserved.

Pathways of proton transfer in the light-driven pump bacteriorhodopsin

NASA Technical Reports Server (NTRS)

Lanyi, J. K.

1993-01-01

The mechanism of proton transport in the light-driven pump bacteriorhodopsin is beginning to be understood. Light causes the all-trans to 13-cis isomerization of the retinal chromophore. This sets off a sequential and directed series of transient decreases in the pKa's of a) the retinal Schiff base, b) an extracellular proton release complex which includes asp-85, and c) a cytoplasmic proton uptake complex which includes asp-96. The timing of these pKa changes during the photoreaction cycle causes sequential proton transfers which result in the net movement of a proton across the protein, from the cytoplasmic to the extracellular surface.

Proton beams in radiotherapy

NASA Astrophysics Data System (ADS)

Khoroshkov, V. S.; Minakova, E. I.

1998-11-01

A branch of radiology, proton therapy employs fast protons as a tool for the treatment of various, mainly oncological, diseases. The features of tissue ionization by protons (Bragg peak) facilitate a further step towards solving the principal challenge in radiology: to deliver a sufficiently high and homogeneous dose to virtually any tumour, while sparing healthy neighbouring tissues, organs and structures. The state of the art of proton therapy is described, as well as the main technical, physics and clinical results gained since the 1950s at high-energy physics centres worldwide. The future of proton therapy is connected with the construction of hospital-based facilities with dedicated medical accelerators and modern technical instrumentation.

On-ground Simulation of the Proton Spectrum in Space

NASA Astrophysics Data System (ADS)

Liu, Hai; Guan, Minchao; He, Shiyu; Yang, Dezhuang; Wang, Huaiyi; Abraimov, V. V.

2009-01-01

The distribution of proton energy losses in optical parts including optical lenses and mirrors was calculated using SRIM program, based on Mont Carlo method. The effect of proton energy on the optical spectrum of lenses and mirrors was also investigated through irradiation experiments, with the proton energy varying from 0.03 to 1 MeV. An approach of on-ground simulation of the proton spectrum in space was proposed taking into account the different characteristics of proton spectra in the radiation belt, solar cosmic ray, and galactic cosmic rays in GEO as well as the corresponding distribution of energy loss in optical parts.

First results on the measurements of the proton beam polarization at internal target at Nuclotron1

NASA Astrophysics Data System (ADS)

Ladygin, V. P.; Gurchin, Yu V.; Isupov, A. Yu; Janek, M.; Khrenov, A. N.; Kurilkin, P. K.; Livanov, A. N.; Piyadin, S. M.; Reznikov, S. G.; Skhomenko, Ya T.; Terekhin, A. A.; Tishevsky, A. V.; Averyanov, A. V.; Bazylev, S. N.; Belov, A. S.; Butenko, A. V.; Chernykh, E. V.; Filatov, Yu N.; Fimushkin, V. V.; Krivenkov, D. O.; Kondratenko, A. M.; Kondratenko, M. A.; Kovalenko, A. D.; Slepnev, I. V.; Slepnev, V. M.; Shutov, A. V.; Sidorin, A. O.; Vnukov, I. E.; Volkov, V. S.

2017-12-01

The spin program at NICA using SPD and MPD requires high intensity polarized proton beam with high value of the beam polarization. First results on the measurements of the proton beam polarization performed at internal target at Nuclotron are reported. The polarization of the proton beam provided by new source of polarized ions has been measured at 500 MeV using quasielastic proton-proton scattering and DSS setup at internal target. The obtained value of the vertical polarization of ∼35% is consistent with the calculations taking into account the current magnetic optics of the Nuclotron injection line.

Transient proton inflows during illumination of anaerobic Halobacterium halobium cells

NASA Technical Reports Server (NTRS)

Helgerson, S. L.; Stoeckenius, W.

1985-01-01

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

Molecular and Histopathological Changes in Mouse Intestinal Tissue After Proton Exposure

NASA Technical Reports Server (NTRS)

Purgason, Ashley; Wu, Honglu

2010-01-01

Whole body exposure to protons in mice causes significant apoptosis in the crypts of the small intestine. Increasing numbers of crypts contained more apoptotic lesions as the dose of exposure increased. 16 genes associated with apoptotic pathways were shown to have significantly altered expression as compared to control samples for at least one of the doses of proton exposure 1 gene, Trp53inp1, was significantly up-regulated across all three doses. Those animals exposed to 0.1 Gy of proton irradiation showed greater amounts of significant alterations in gene expression as compared to 1 Gy and 2 Gy exposures. The differences in gene expression changes of low and high dose proton irradiated mice may offer insight into the molecular mechanisms of the possible high sensitivity at low proton doses. RAIDD (CRADD) may be responsible for the hypersensitivity observed in the duodenum of mice exposed to low doses of protons. Caspase-1 may also play a role in the hypersensitivity seen following proton irradiation at a dose of 0.1 Gy. FOXO3A may be involved in the down-regulation of GILZ observed at high doses of proton exposure.

Proton irradiation effects on gallium nitride-based devices

NASA Astrophysics Data System (ADS)

Karmarkar, Aditya P.

Proton radiation effects on state-of-the-art gallium nitride-based devices were studied using Schottky diodes and high electron-mobility transistors. The device degradation was studied over a wide range of proton fluences. This study allowed for a correlation between proton irradiation effects between different types of devices and enhanced the understanding of the mechanisms responsible for radiation damage in GaN-based devices. Proton irradiation causes reduced carrier concentration and increased series resistance and ideality factor in Schottky diodes. 1.0-MeV protons cause greater degradation than 1.8-MeV protons because of their higher non-ionizing energy loss. The displacement damage in Schottky diodes recovers during annealing. High electron-mobility transistors exhibit extremely high radiation tolerance, continuing to perform up to a fluence of ˜1014 cm-2 of 1.8-MeV protons. Proton irradiation creates defect complexes in the thin-film structure. Decreased sheet carrier mobility due to increased carrier scattering and decreased sheet carrier density due to carrier removal by the defect centers are the primary damage mechanisms. Interface disorder at either the Schottky or the Ohmic contact plays a relatively unimportant part in overall device degradation in both Schottky diodes and high electron-mobility transistors.

A review of dosimetric and toxicity modeling of proton versus photon craniospinal irradiation for pediatrics medulloblastoma.

PubMed

Ho, Evangeline S Q; Barrett, Sarah A; Mullaney, Laura M

2017-08-01

Craniospinal irradiation (CSI) is the standard radiation therapy treatment for medulloblastoma. Conventional CSI photon therapy (Photon-CSI) delivers significant dose to surrounding normal tissue (NT). Research into pediatric CSI with proton therapy (Proton-CSI) has increased, with the aim of exploiting the potential to reduce NT dose and associated post-treatment complications. This review aims to compare treatment outcomes of pediatric medulloblastoma patients between Proton- and Photon-CSI treatments. A search and review of studies published between 1990 and 2016 comparing pediatric (2-18 years) medulloblastoma Proton- and Photon-CSI in three aspects - normal organ sparing and target coverage; normal organ dysfunction and second malignancy risks - was completed. Fifteen studies were selected for review and the results were directly compared. Proton-CSI reported improved out-of-field organ sparing while target coverage improvements were inconsistent. Normal organ dysfunction risks were predicted to be lower following Proton-CSI. Secondary malignancy risks (SMRs) were generally lower with Proton-CSI based on several different risk models. Proton-CSI conferred better treatment outcomes than Photon-CSI for pediatric medulloblastoma patients. This review serves to compare the current literature in the absence of long-term data from prospective studies.

Proton trapping in SiO 2 layers thermally grown on Si and SiC

NASA Astrophysics Data System (ADS)

Afanas'ev, V. V.; Ciobanu, F.; Pensl, G.; Stesmans, A.

2002-11-01

Positive charging of thermal SiO 2 layers on (1 0 0)Si and (0 0 0 1)6H-, 4H-SiC related to trapping of protons is studied using low-energy proton implantation into the oxide, and compared to the trapping of holes generated by 10-eV photons. Proton trapping has an initial probability close to 100% and shows little sensitivity to the annealing-induced oxygen deficiency of SiO 2. In contrast to protons, hole trapping in as-grown SiO 2 shows a much lower efficiency which increases upon oxide annealing, in qualitative correlation with the higher density of O 3Si• defects (E' centers) detected by electron spin resonance after hole injection. Despite these differences, the neutralization of positive charges induced by holes and protons has the same cross-section, and in both cases is accompanied by liberation of atomic H suggesting that protons account for positive charge in both cases. The rupture of Si-O bonds in the oxide observed upon proton injection suggests, as a first basic step, the bonding of a proton to a bridging oxygen atom in SiO 2 network.

Measurement and investigation of proton irradiation-induced charge transfer inefficiency in PPD CIS at different integration times

NASA Astrophysics Data System (ADS)

Xue, Yuanyuan; Wang, Zujun; Zhang, Fengqi; Bian, Jingying; Yao, Zhibin; He, Baoping; Liu, Minbo; Sheng, Jiangkun; Ma, Wuying; Dong, Guantao; Jin, Junshan

2018-04-01

Charge transfer inefficiency (CTI) is an important parameter for photodiode (PPD) CMOS image sensors (CISs). A test system was built and used to measure the CTI of PPD CIS devices at different integration times. The radiation effects of 3 MeV and 10 MeV protons on the CTI were investigated. The experiments were carried out at the EN Tandem Van de Graaff accelerator at proton fluences in the range 1010 to 1011 p/cm2. The CTI was measured within the 2 h following proton radiations. The dependence of CTI on integration time, proton energy and fluence were investigated. The CTI was observed to increase after proton irradiation: with the effect of irradiation with 3 MeV proton being more severe than that with 10 MeV protons. The CTI was also observed to decrease with increasing integration time, which is thought to be related to the charge density in the space charge region (SCR) of the CIS devices. This work has provided a simple method to measure the CTI and helped us to understand proton radiation effects on the CTI of PPD CISs.

Proton movement and coupling in the POT family of peptide transporters

PubMed Central

Parker, Joanne L.; Li, Chenghan; Brinth, Allete; Wang, Zhi; Vogeley, Lutz; Solcan, Nicolae; Ledderboge-Vucinic, Gregory; Swanson, Jessica M. J.; Caffrey, Martin; Voth, Gregory A.

2017-01-01

POT transporters represent an evolutionarily well-conserved family of proton-coupled transport systems in biology. An unusual feature of the family is their ability to couple the transport of chemically diverse ligands to an inwardly directed proton electrochemical gradient. For example, in mammals, fungi, and bacteria they are predominantly peptide transporters, whereas in plants the family has diverged to recognize nitrate, plant defense compounds, and hormones. Although recent structural and biochemical studies have identified conserved sites of proton binding, the mechanism through which transport is coupled to proton movement remains enigmatic. Here we show that different POT transporters operate through distinct proton-coupled mechanisms through changes in the extracellular gate. A high-resolution crystal structure reveals the presence of ordered water molecules within the peptide binding site. Multiscale molecular dynamics simulations confirm proton transport occurs through these waters via Grotthuss shuttling and reveal that proton binding to the extracellular side of the transporter facilitates a reorientation from an inward- to outward-facing state. Together these results demonstrate that within the POT family multiple mechanisms of proton coupling have likely evolved in conjunction with variation of the extracellular gate. PMID:29180426

Proton movement and coupling in the POT family of peptide transporters.

PubMed

Parker, Joanne L; Li, Chenghan; Brinth, Allete; Wang, Zhi; Vogeley, Lutz; Solcan, Nicolae; Ledderboge-Vucinic, Gregory; Swanson, Jessica M J; Caffrey, Martin; Voth, Gregory A; Newstead, Simon

2017-12-12

POT transporters represent an evolutionarily well-conserved family of proton-coupled transport systems in biology. An unusual feature of the family is their ability to couple the transport of chemically diverse ligands to an inwardly directed proton electrochemical gradient. For example, in mammals, fungi, and bacteria they are predominantly peptide transporters, whereas in plants the family has diverged to recognize nitrate, plant defense compounds, and hormones. Although recent structural and biochemical studies have identified conserved sites of proton binding, the mechanism through which transport is coupled to proton movement remains enigmatic. Here we show that different POT transporters operate through distinct proton-coupled mechanisms through changes in the extracellular gate. A high-resolution crystal structure reveals the presence of ordered water molecules within the peptide binding site. Multiscale molecular dynamics simulations confirm proton transport occurs through these waters via Grotthuss shuttling and reveal that proton binding to the extracellular side of the transporter facilitates a reorientation from an inward- to outward-facing state. Together these results demonstrate that within the POT family multiple mechanisms of proton coupling have likely evolved in conjunction with variation of the extracellular gate. Copyright © 2017 the Author(s). Published by PNAS.

The design features cells use to build their transmembrane proton gradient

NASA Astrophysics Data System (ADS)

Gunner, M. R.; Koder, Ronald

2017-02-01

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

Solar Wind Proton Temperature Anisotropy: Linear Theory and WIND/SWE Observations

NASA Technical Reports Server (NTRS)

Hellinger, P.; Travnicek, P.; Kasper, J. C.; Lazarus, A. J.

2006-01-01

We present a comparison between WIND/SWE observations (Kasper et al., 2006) of beta parallel to p and T perpendicular to p/T parallel to p (where beta parallel to p is the proton parallel beta and T perpendicular to p and T parallel to p are the perpendicular and parallel proton are the perpendicular and parallel proton temperatures, respectively; here parallel and perpendicular indicate directions with respect to the ambient magnetic field) and predictions of the Vlasov linear theory. In the slow solar wind, the observed proton temperature anisotropy seems to be constrained by oblique instabilities, by the mirror one and the oblique fire hose, contrary to the results of the linear theory which predicts a dominance of the proton cyclotron instability and the parallel fire hose. The fast solar wind core protons exhibit an anticorrelation between beta parallel to c and T perpendicular to c/T parallel to c (where beta parallel to c is the core proton parallel beta and T perpendicular to c and T parallel to c are the perpendicular and parallel core proton temperatures, respectively) similar to that observed in the HELIOS data (Marsch et al., 2004).

A cluster of carboxylic groups in PsbO protein is involved in proton transfer from the water oxidizing complex of Photosystem II.

PubMed

Shutova, Tatiana; Klimov, Vyacheslav V; Andersson, Bertil; Samuelsson, Göran

2007-06-01

The hypothesis presented here for proton transfer away from the water oxidation complex of Photosystem II (PSII) is supported by biochemical experiments on the isolated PsbO protein in solution, theoretical analyses of better understood proton transfer systems like bacteriorhodopsin and cytochrome oxidase, and the recently published 3D structure of PS II (Pdb entry 1S5L). We propose that a cluster of conserved glutamic and aspartic acid residues in the PsbO protein acts as a buffering network providing efficient acceptors of protons derived from substrate water molecules. The charge delocalization of the cluster ensures readiness to promptly accept the protons liberated from substrate water. Therefore protons generated at the catalytic centre of PSII need not be released into the thylakoid lumen as generally thought. The cluster is the beginning of a localized, fast proton transfer conduit on the lumenal side of the thylakoid membrane. Proton-dependent conformational changes of PsbO may play a role in the regulation of both supply of substrate water to the water oxidizing complex and the resultant proton transfer.

The role of charge-exchange cross-section for pickup protons and neutrals in the inner heliosheath

NASA Astrophysics Data System (ADS)

Chalov, S. V.

2018-06-01

The process of deceleration of the solar wind downstream of the termination shock is studied on the basis of a one-dimensional multi-component model. It is assumed that the solar wind consists of thermal protons, electrons and interstellar pickup protons. The protons interact with interstellar hydrogen atoms by charge-exchange. Two cases are considered. In the first one, the charge-exchange cross-section for thermal protons and hydrogen atoms is the same as for pickup protons and atoms. Under this condition, there is a strong dependence of the solar wind velocity on the downstream temperature of pickup protons. When the proton temperature is close to 10 keV, the change in the velocity with the distance from the termination shock is similar to that measured on the Voyager 1 spacecraft: linear velocity decrease is accompanied by an extended transition region with near-zero velocity. However, with a more careful approach to the choice of the charge-exchange cross-section, the situation changes dramatically. The strong dependence of the solar wind speed on the pickup proton temperature disappears and the transition region in the heliosheath disappears as well, at least at reasonable distances from the TS.

Ring current proton decay by charge exchange

NASA Technical Reports Server (NTRS)

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

1975-01-01

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

Application of proton boron fusion reaction to radiation therapy: A Monte Carlo simulation study

NASA Astrophysics Data System (ADS)

Yoon, Do-Kun; Jung, Joo-Young; Suh, Tae Suk

2014-12-01

Three alpha particles are emitted from the point of reaction between a proton and boron. The alpha particles are effective in inducing the death of a tumor cell. After boron is accumulated in the tumor region, the emitted from outside the body proton can react with the boron in the tumor region. An increase of the proton's maximum dose level is caused by the boron and only the tumor cell is damaged more critically. In addition, a prompt gamma ray is emitted from the proton boron reaction point. Here, we show that the effectiveness of the proton boron fusion therapy was verified using Monte Carlo simulations. We found that a dramatic increase by more than half of the proton's maximum dose level was induced by the boron in the tumor region. This increase occurred only when the proton's maximum dose point was located within the boron uptake region. In addition, the 719 keV prompt gamma ray peak produced by the proton boron fusion reaction was positively detected. This therapy method features the advantages such as the application of Bragg-peak to the therapy, the accurate targeting of tumor, improved therapy effects, and the monitoring of the therapy region during treatment.

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.

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.

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

PubMed

Gunner, M R; Koder, Ronald

2017-02-07

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

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

Shrink-wrapping water to conduct protons

NASA Astrophysics Data System (ADS)

Shimizu, George K. H.

2017-11-01

For proton-conducting metal-organic frameworks (MOFs) to find application as the electrolyte in proton-exchange membrane fuel cells, materials with better stability and conductivity are required. Now, a structurally flexible MOF that is also highly stable is demonstrated to possess high proton conductivity over a range of humidities.

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.

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