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Background and Purpose: Ion beams exhibit an increased relative biological effectiveness (RBE) with respect to photons. This study determined the RBE of oxygen ion beams as a function of linear energy transfer (LET) and dose in the rat spinal cord., Materials and Methods: The spinal cord of rats was irradiated at four different positions of a 6 cm spread-out Bragg-peak (LET: 26, 66, 98 and 141 keV/µm) using increasing levels of single and split oxygen ion doses. Dose-response curves were established for the endpoint paresis grade II and based on ED 50 (dose at 50 % effect probability), the RBE was determined and compared to model predictions., Results: When LET increased from 26 to 98 keV/µm, ED 50 decreased from 17.2 ± 0.3 Gy to 13.5 ± 0.4 Gy for single and from 21.7 ± 0.4 Gy to 15.5 ± 0.5 Gy for split doses, however, at 141 keV/µm, ED 50 rose again to 15.8 ± 0.4 Gy and 17.2 ± 0.4 Gy, respectively. As a result, the RBE increased from 1.43 ± 0.05 to 1.82 ± 0.08 (single dose) and from 1.58 ± 0.04 to 2.21 ± 0.08 (split dose), respectively, before declining again to 1.56 ± 0.06 for single and 1.99 ± 0.06 for split doses at the highest LET. Deviations from RBE-predictions were model-dependent., Conclusion: This study established first RBE data for the late reacting central nervous system after single and split doses of oxygen ions. The data was used to validate the RBE-dependence on LET and dose of three RBE-models. This study extends the existing data base for protons, helium and carbon ions and provides important information for future patient treatments with oxygen ions., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Karger received funding for the present study by the German Cancer Aid (grant number 111,434 and 70112975). Dr. Scholz holds a European Patent 10 718 875.7 with royalties paid by Siemens and RaySearch. All other authors do not report any financial interests., (© 2024 The Author(s).)

Charged particle radiotherapy, mainly using protons and carbon ions, provides physical characteristics allowing for a volume conformal irradiation and a reduction of the integral dose to normal tissue. Carbon ion therapy additionally features an increased biological effectiveness resulting in peculiar molecular effects. Immunotherapy, mostly performed with immune checkpoint inhibitors, is nowadays considered a pillar in cancer therapy. Based on the advantageous features of charged particle radiotherapy, we review pre-clinical evidence revealing a strong potential of its combination with immunotherapy. We argue that the combination therapy deserves further investigation with the aim of translation in clinics, where a few studies have been set up already., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Optical generation of kilo-tesla scale magnetic fields enables prospective technologies and fundamental studies with unprecedentedly high magnetic field energy density. A question is the optimal configuration of proposed setups, where plenty of physical phenomena accompany the generation and complicate both theoretical studies and experimental realizations. Short laser drivers seem more suitable in many applications, though the process is tangled by an intrinsic transient nature. In this work, an artificial neural network is engaged for unravelling main features of the magnetic field excited with a picosecond laser pulse. The trained neural network acquires an ability to read the magnetic field values from experimental data, extremely facilitating interpretation of the experimental results. The conclusion is that the short sub-picosecond laser pulse may generate a quasi-stationary magnetic field structure living on a hundred picosecond time scale, when the induced current forms a closed circuit., (© 2022. The Author(s).)

Background and Purpose: Determination of the relative biological effectiveness (RBE) of helium ions as a function of linear energy transfer (LET) for single and split doses using the rat cervical spinal cord as model system for late-responding normal tissue., Material and Methods: The rat cervical spinal cord was irradiated at four different positions within a 6 cm spread-out Bragg-peak (SOBP) (LET 2.9, 9.4, 14.4 and 20.7 keV/µm) using increasing levels of single or split doses of helium ions. Dose-response curves were determined and based on TD 50 -values (dose at 50% effect probability using paresis II as endpoint), RBE-values were derived for the endpoint of radiation-induced myelopathy., Results: With increasing LET, RBE-values increased from 1.13 ± 0.04 to 1.42 ± 0.05 (single dose) and 1.12 ± 0.03 to 1.50 ± 0.04 (split doses) as TD 50 -values decreased from 21.7 ± 0.3 Gy to 17.3 ± 0.3 Gy (single dose) and 30.6 ± 0.3 Gy to 22.9 ± 0.3 Gy (split doses), respectively. RBE-models (LEM I and IV, mMKM) deviated differently for single and split doses but described the RBE variation in the high-LET region sufficiently accurate., Conclusion: This study established the LET-dependence of the RBE for late effects in the central nervous system after single and split doses of helium ions. The results extend the existing database for protons and carbon ions and allow systematic testing of RBE-models. While the RBE-values of helium were generally lower than for carbon ions, the increase at the distal edge of the Bragg-peak was larger than for protons, making detailed RBE-modeling necessary., Competing Interests: Conflict of interest Dr. Karger and Dr. Debus received funding for the present study by the German Cancer Aid (grant number 111434 and 70112975). Dr. Scholz holds a European Patent 10 718 875.7 with royalties paid by Siemens and RaySearch. All other authors do not report any financial interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The Southeast European (SEE) region of 10 countries and about 43 million people differs from Western Europe in that most SEE countries lack active cancer registries and have fewer diagnostic imaging devices and radiotherapy (RT) units. The main objective of this research is to initiate a common platform for gathering SEE regional cancer data from the ground up to help these countries develop common cancer management strategies., Methods: To obtain detailed on-the-ground information, we developed separate questionnaires for two SEE groups: a) ONCO - oncologists regarding cancer treatment modalities and the availability of diagnostic imaging and radiotherapy equipment; and b) REG - national radiation protection and safety regulatory bodies regarding diagnostic imaging and radiotherapy equipment in SEE facilities., Results: Based on responses from 13/17 ONCO participants (at least one from each country) and from 9/10 REG participants (all countries but Albania), cancer incidence rates are higher in those SEE countries that have greater access to diagnostic imaging equipment while cancer mortality-to-incidence (MIR) ratios are higher in countries that lack radiotherapy equipment., Conclusion: By combining unique SEE region information with data available from major global databases, we demonstrated that the availability of diagnostic imaging and radiotherapy equipment in the SEE countries is related to their economic development. While immediate diagnostic imaging and radiation therapy capacity building is necessary, it is also essential to develop both national and SEE-regional cancer registries in order to understand the heterogeneity of each country's needs and to establish regional collaborative strategies for combating cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The advantageous depth dose profile of ion beams together with state of the art beam delivery and treatment planning systems allow for highly conformal tumor treatments in patients. First treatments date back to 1954 at the Lawrence Berkeley Laboratory (LBL) and in Europe, ion beam therapy started in the mid-1990s at the Paul-Scherrer Institute (PSI) with protons and at the Helmholtz Center for Heavy Ion Research (GSI) with carbon ions, followed by the Heidelberg Ion Therapy Center (HIT) in Heidelberg. This review describes the historical development of ion beam therapy in Germany based on the pioneering work at LBL and in the context of simultaneous developments in other countries as well as recent developments., (Copyright © 2021. Published by Elsevier GmbH.)

Ion beams used for radiotherapy exhibit an increased relative biological effectiveness (RBE), which depends on several physical treatment parameters as well as on biological factors of the irradiated tissues. While the RBE is an experimentally well-defined quantity, translation to patients is complex and requires radiobiological studies, dedicated models to calculate the RBE in treatment planning as well as strategies for dose prescription. Preclinical in vivo studies and analysis of clinical outcome are important to validate and refine RBE-models. This review describes the concept of the experimental and clinical RBE and explains the fundamental dependencies of the RBE based on in vitro experiments. The available preclinical in vivo studies on normal tissue and tumor RBE for ions heavier than protons are reviewed in the context of the historical and present development of ion beam radiotherapy. In addition, the role of in vivo RBE-values in the development and benchmarking of RBE-models as well as the transition of these models to clinical application are described. Finally, limitations in the translation of experimental RBE-values into clinical application and the direction of future research are discussed., (Copyright © 2020. Published by Elsevier GmbH.)

Landau damping is an essential mechanism for ensuring collective beam stability in particle accelerators. Precise knowledge of the strength of Landau damping is key to making accurate predictions on beam stability for state-of-the-art high-energy colliders. In this Letter, we demonstrate an experimental procedure that would allow quantifying the strength of Landau damping and the limits of beam stability using an active transverse feedback as a controllable source of beam coupling impedance. In a proof-of-principle test performed at the Large Hadron Collider, stability diagrams for a range of Landau octupole strengths have been measured. In the future, the procedure could become an accurate way of measuring stability diagrams throughout the machine cycle.

A beam profile monitor based on a supersonic gas-curtain is currently under development for transverse profile diagnostics of electron and proton beams in the High Luminosity LHC. This monitor uses a thin supersonic gas curtain that crosses the primary beam to be characterized under an angle of 45 degrees. The fluorescence caused by the interaction between the beam and gas-curtain is detected using a specially designed imaging system to determine the 2D transverse profile of the primary beam. Another prototype monitor based on beam induced ionization is installed at The Cockcroft Institute. This paper presents the design features of both the monitors, the gas-jet curtain formation and various experimental tests, including profile measurements of an electron beam, using helium, nitrogen and neon as gases. Such a non-invasive online beam profile monitor would be highly desirable also for medical LINAC's and storage rings as it can characterize the beam without stopping machine operation. The paper discusses opportunities for simplifying the monitor design for integration into a medical accelerator and expected monitor performance., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Background: To determine the relative biological effectiveness (RBE) and α/β-values after fractionated carbon ion irradiations of the rat spinal cord with varying linear energy transfer (LET) to benchmark RBE-model calculations., Material and Methods: The rat spinal cord was irradiated with 6 fractions of carbon ions at 6 positions within a 6 cm spread-out Bragg-peak (SOBP, LET: 16-99 keV/μm). TD 50 -values (dose at 50% complication probability) were determined from dose-response curves for the endpoint radiation induced myelopathy (paresis grade II) within 300 days after irradiation. Based on TD 50 -values of 15 MV photons, RBE-values were calculated and adding previously published data, the LET and fractional dose-dependence of the RBE was used to benchmark the local effect model (LEM I and IV)., Results: At six fractions, TD 50 -values decreased from 39.1 ± 0.4 Gy at 16 keV/μm to 17.5 ± 0.3 Gy at 99 keV/μm and the RBE increased accordingly from 1.46 ± 0.05 to 3.26 ± 0.13. Experimental α/β-ratios ranged from 6.9 ± 1.1 Gy to 44.3 ± 7.2 Gy and increased strongly with LET. Including all available data, comparison with model-predictions revealed that (i) LEM IV agrees better in the SOBP, while LEM I fits better in the entrance region, (ii) LEM IV describes the slope of the RBE within the SOBP better than LEM I, and (iii) in contrast to the strong LET-dependence, the RBE-deviations depend only weakly on fractionation within the measured range., Conclusions: This study extends the available RBE data base to significantly lower fractional doses and performes detailed tests of the RBE-models LEM I and IV. In this comparison, LEM IV agrees better with the experimental data in the SOBP than LEM I. While this could support a model replacement in treatment planning, careful dosimetric analysis is required for the individual patient to evaluate potential clinical consequences.

Background: The present work summarizes the research activities on radiation-induced late effects in the rat spinal cord carried out within the "clinical research group ion beam therapy" funded by the German Research Foundation (DFG, KFO 214)., Methods and Materials: Dose-response curves for the endpoint radiation-induced myelopathy were determined at 6 different positions (LET 16-99 keV/μm) within a 6 cm spread-out Bragg peak using either 1, 2 or 6 fractions of carbon ions. Based on the tolerance dose TD 50 of carbon ions and photons, the relative biological effectiveness (RBE) was determined and compared with predictions of the local effect model (LEM I and IV). Within a longitudinal magnetic resonance imaging (MRI)-based study the temporal development of radiation-induced changes in the spinal cord was characterized. To test the protective potential of the ACE (angiotensin converting enzyme)-inhibitor ramipril™, an additional dose-response experiment was performed., Results: The RBE-values increased with LET and the increase was found to be larger for smaller fractional doses. Benchmarking the RBE-values as predicted by LEM I and LEM IV with the measured data revealed that LEM IV is more accurate in the high-LET, while LEM I is more accurate in the low-LET region. Characterization of the temporal development of radiation-induced changes with MRI demonstrated a shorter latency time for carbon ions, reflected on the histological level by an increased vessel perforation after carbon ion as compared to photon irradiations. For the ACE-inhibitor ramipril™, a mitigative rather than protective effect was found., Conclusions: This comprehensive study established a large and consistent RBE data base for late effects in the rat spinal cord after carbon ion irradiation which will be further extended in ongoing studies. Using MRI, an extensive characterization of the temporal development of radiation-induced alterations was obtained. The reduced latency time for carbon ions is expected to originate from a dynamic interaction of various complex pathological processes. A dominant observation after carbon ion irradiation was an increase in vessel perforation preferentially in the white matter. To enable a targeted pharmacological intervention more details of the molecular pathways, responsible for the development of radiation-induced myelopathy are required.

In this paper we report the re-analysis of the data published in (Piersanti et al. 2014) documenting the charged secondary particles production induced by the interaction of a 220 MeV/u 12C ion beam impinging on a polymethyl methacrylate (PMMA) target, measured in 2012 at the GSI facility in Darmstadt (Germany). This re-analysis takes into account the inhomogeneous light response of the LYSO crystal in the experimental setup measured in a subsequent experiment (2014) performed in the Heidelberg Ion- Beam Therapy Center. A better description of the detector and re-calculation of the geometrical efficiencies have been implemented as well, based on an improved approach that accounts also for the energy dependence of the emission spectrum. The new analysis has small effect on the total secondary charged flux, but has an impact on the production yield and emission velocity distributions of the different particle species (protons, deuterons and tritons) at different angles with respect to the beam direction (60° and 90°). All these observables indeed depend on the particle identification algorithms and hence on the LYSO detector energy response. The results of the data re-analysis presented here are intended to supersede and replace the results published in (Piersanti et al. 2014)., (© 2017 Institute of Physics and Engineering in Medicine.)

Experiments to investigate the space charge compensation of pulsed high-current heavy ion beams are performed at the GSI ion source text benches with a 4-grid analyzer provided by CEA/Saclay. The technical design of the 4-grid analyzer is revised to verify its functionality for measurements at pulsed high-current heavy ion beams. The experimental investigation of space charge compensation processes is needed to increase the performance and quality of current and future accelerator facilities. Measurements are performed directly downstream a triode extraction system mounted to a multi-cusp ion source at a high-current test bench as well as downstream the post-acceleration system of the high-current test injector (HOSTI) with ion energies up to 120 keV/u for helium and argon. At HOSTI, a cold or hot reflex discharge ion source is used to change the conditions for the measurements. The measurements were performed with helium, argon, and xenon and are presented. Results from measurements with single aperture extraction systems are shown.

Simulation of ion beam extraction from an Electron Cyclotron Resonance Ion Source (ECRIS) is a fully 3 dimensional problem, even if the extraction geometry has cylindrical symmetry. Because of the strong magnetic flux density, not only the electrons are magnetized but also the Larmor radius of ions is much smaller than the geometrical dimension of the plasma chamber (Ø 64 × 179 mm). If we assume that the influence of collisions is small on the path of particles, we can do particle tracking through the plasma if the initial coordinates of particles are known. We generated starting coordinates of plasma ions by simulation of the plasma electrons, accelerated stochastically by the 14.5 GHz radio frequency power fed to the plasma. With that we were able to investigate the influence of different electron energies on the extracted beam. Using these assumptions, we can reproduce the experimental results obtained 10 years ago, where we monitored the beam profile with the help of viewing targets. Additionally, methods have been developed to investigate arbitrary 2D cuts of the 6D phase space. To this date, we are able to discuss full 4D information. Currently, we extend our analysis tool towards 5D and 6D, respectively.

This paper focuses on constraining the erosion rate in the area of the Allchar Sb-As-Tl-Au deposit (Macedonia). It contains the largest known reserves of lorandite (TlAsS 2 ), which is essential for the LORanditeEXperiment (LOREX), aimed at determining the long-term solar neutrino flux. Because the erosion history of the Allchar area is crucial for the success of LOREX, we applied terrestrial in situ cosmogenic nuclides including both radioactive ( 26 Al and 36 Cl) and stable ( 3 He and 21 Ne) nuclides in quartz, dolomite/calcite, sanidine, and diopside. The obtained results suggest that there is accordance in the values obtained by applying 26 Al, 36 Cl, and 21 Ne for around 85% of the entire sample collection, with resulting erosion rates varying from several tens of m/Ma to ∼165 m/Ma. The samples from four locations (L-8 CD, L1b/R, L1c/R, and L-4/ADR) give erosion rates between 300 and 400 m/Ma. Although these localities reveal remarkably higher values, which may be explained by burial events that occurred in part of Allchar, the erosion rate estimates mostly in the range between 50 and 100 m/Ma. This range further enables us to estimate the vertical erosion rate values for the two main ore bodies Crven Dol and Centralni Deo. We also estimate that the lower and upper limits of average paleo-depths for the ore body Centralni Deo from 4.3 Ma to the present are 250-290 and 750-790 m, respectively, whereas the upper limit of paleo-depth for the ore body Crven Dol over the same geological age is 860 m. The estimated paleo-depth values allow estimating the relative contributions of 205 Pb derived from pp-neutrino and fast cosmic-ray muons, respectively, which is an important prerequisite for the LOREX experiment.

Romosozumab inhibits sclerostin, thereby increasing bone formation and decreasing bone resorption. This dual effect of romosozumab leads to rapid and substantial increases in areal bone mineral density (aBMD) as measured by dual-energy X-ray absorptiometry (DXA). In a phase 1b, randomized, double-blind, placebo-controlled study, romosozumab or placebo was administered to 32 women and 16 men with low aBMD for 3 months, with a further 3-month follow-up: women received six doses of 1 or 2mg/kg every 2 weeks (Q2W) or three doses of 2 or 3mg/kg every 4 weeks (Q4W); men received 1mg/kg Q2W or 3mg/kg Q4W. Quantitative computed tomography (QCT) scans at lumbar (L1-2) vertebrae and high-resolution QCT (HR-QCT) scans at thoracic vertebra (T12) were analyzed in a subset of subjects at baseline, month 3, and month 6. The QCT subset included 24 romosozumab and 9 placebo subjects and the HR-QCT subset included 11 romosozumab and 3 placebo subjects. The analyses pooled the romosozumab doses. Linear finite element modeling of bone stiffness was performed. Compared with placebo, the romosozumab group showed improvements at month 3 for trabecular BMD by QCT and HR-QCT, HR-QCT trabecular bone volume fraction (BV/TV) and separation, density-weighted cortical thickness, and QCT stiffness (all p<0.05). At month 6, improvements from baseline were observed in QCT trabecular BMD and stiffness, and in HR-QCT BMD, trabecular BV/TV and separation, density-weighted cortical thickness, and stiffness in the romosozumab group (all p<0.05 compared with placebo). The mean (SE) increase in HR-QCT stiffness with romosozumab from baseline was 26.9% ± 6.8% and 35.0% ±6.8% at months 3 and 6, respectively; subjects administered placebo had changes of -2.7% ± 13.4% and -6.4% ± 13.4%, respectively. In conclusion, romosozumab administered for 3 months resulted in rapid and large improvements in trabecular and cortical bone mass and structure as well as whole bone stiffness, which continued 3 months after the last romosozumab dose., (Copyright © 2015. Published by Elsevier Inc.)

Purpose: To measure the relative biological effectiveness (RBE) of carbon ions relative to 15 MeV photons in the rat spinal cord for different linear energy transfers (LET) to validate model calculations., Methods and Materials: The cervical spinal cord of rats was irradiated with 2 fractions of carbon ions at six positions of a 6 cm spread-out Bragg-peak (SOBP, 16-99 keV/μm). TD50-values (dose at 50% complication probability) were determined from dose-response curves for the endpoint radiation induced myelopathy (paresis grade II) within 300 days after irradiation. Using previously published TD50-values for photons (Karger et al., 2006; Debus et al., 2003), RBE-values were determined and compared with predictions of two versions of the local effect model (LEM I and IV)., Results: TD50-values for paresis grade II were 26.7 ± 0.4 Gy (16 keV/μm), 24.0 ± 0.3 Gy (21 keV/μm), 22.5 ± 0.3 Gy (36 keV/μm), 20.1 ± 1.2 Gy (45 keV/μm), 17.7 ± 0.3 Gy (66 keV/μm), and 14.9 ± 0.3 Gy (99 keV/μm). RBE-values increased from 1.28 ± 0.03 (16 keV/μm) up to 2.30 ± 0.06 at 99 keV/μm. At the applied high fractional doses, LEM I fits best at 16 keV/μm and deviates progressively toward higher LETs while LEM IV agrees best at 99 keV/μm and shows increasing deviations, especially below 66 keV/μm., Conclusions: The measured data improve the knowledge on the accuracy of RBE-calculations for carbon ions., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The sensitivity of the Giant LOop Binary LEsion model for cell survival probabilities after arbitrary photon irradiation schedules on its parameters is presented. Since these parameters are closely linked to observable features of cell repair, the modelled influence of the parameters on cell survival gives indications about the relation between cell line-specific repair characteristics and the radiation response. To visualise the general findings about the impact of parameter changes on cell survival probabilities, survival curves for an exemplary cell line are shown. Furthermore, the relative change in the effect of radiation after a change in parameter values is investigated over the range of doses and dose rates usually applied in cell survival experiments., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The origin of nonlinear dynamics traces back to the study of the dynamics of planets with the seminal work of Poincaré at the end of the nineteenth century: Les Méthodes Nouvelles de la Mécanique Céleste, Vols. 1-3 (Gauthier Villars, Paris, 1899). In his work he introduced a methodology fruitful for investigating the dynamical properties of complex systems, which led to the so-called "Poincaré surface of section," which allows one to capture the global dynamical properties of a system, characterized by fixed points and separatrices with respect to regular and chaotic motion. For two-dimensional phase space (one degree of freedom) this approach has been extremely useful and applied to particle accelerators for controlling their beam dynamics as of the second half of the twentieth century. We describe here an extension of the concept of 1D fixed points to fixed lines in two dimensions. These structures become the fundamental entities for characterizing the nonlinear motion in the four-dimensional phase space (two degrees of freedom).

This report, compiled by experts on the treatment of mobile targets with advanced radiotherapy, summarizes the main conclusions and innovations achieved during the 4D treatment planning workshop 2013. This annual workshop focuses on research aiming to advance 4D radiotherapy treatments, including all critical aspects of time resolved delivery, such as in-room imaging, motion detection, motion managing, beam application, and quality assurance techniques. The report aims to revise achievements in the field and to discuss remaining challenges and potential solutions. As main achievements advances in the development of a standardized 4D phantom and in the area of 4D-treatment plan optimization were identified. Furthermore, it was noticed that MR imaging gains importance and high interest for sequential 4DCT/MR data sets was expressed, which represents a general trend of the field towards data covering a longer time period of motion. A new point of attention was work related to dose reconstructions, which may play a major role in verification of 4D treatment deliveries. The experimental validation of results achieved by 4D treatment planning and the systematic evaluation of different deformable image registration methods especially for inter-modality fusions were identified as major remaining challenges. A challenge that was also suggested as focus for future 4D workshops was the adaptation of image guidance approaches from conventional radiotherapy into particle therapy. Besides summarizing the last workshop, the authors also want to point out new evolving demands and give an outlook on the focus of the next workshop., (Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: To measure the relative biological effectiveness (RBE) of carbon ions in the rat spinal cord as a function of linear energy transfer (LET)., Methods and Materials: As an extension of a previous study, the cervical spinal cord of rats was irradiated with single doses of carbon ions at 6 positions of a 6-cm spread-out Bragg peak (16-99 keV/μm). The TD50 values (dose at 50% complication probability) were determined according to dose-response curves for the development of paresis grade 2 within an observation time of 300 days. The RBEs were calculated using TD50 for photons of our previous study., Results: Minimum latency time was found to be dose-dependent, but not significantly LET-dependent. The TD50 values for the onset of paresis grade 2 within 300 days were 19.5 ± 0.4 Gy (16 keV/μm), 18.4 ± 0.4 Gy (21 keV/μm), 17.7 ± 0.3 Gy (36 keV/μm), 16.1 ± 1.2 Gy (45 keV/μm), 14.6 ± 0.5 Gy (66 keV/μm), and 14.8 ± 0.5 Gy (99 keV/μm). The corresponding RBEs increased from 1.26 ± 0.05 (16 keV/μm) up to 1.68 ± 0.08 at 66 keV/μm. Unexpectedly, the RBE at 99 keV/μm was comparable to that at 66 keV/μm., Conclusions: The data suggest a linear relation between RBE and LET at high doses for late effects in the spinal cord. Together with additional data from ongoing fractionated irradiation experiments, these data will provide an extended database to systematically benchmark RBE models for further improvements of carbon ion treatment planning., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Time-varying nonlinear oscillatory systems produce phenomena of resonance crossing and trapping of particles in resonance islands. Traditionally, such processes have been analyzed in terms of adiabatic conditions. Considering, as an example, a simplified one-dimensional model describing the "electron-cloud pinch" during a bunch passage in a particle accelerator, here we present an approach to resonance trapping which does not require any adiabatic condition. Instead we introduce the concept of the attraction point and investigate invariance and scaling properties of motion close to the attraction point, considering a single resonance crossing.

The finite difference method trajectory code KOBRA3-INP has been developed now for 25 years to perform the simulation of ion beam extraction in three dimensions. Meanwhile, the code has been validated for different applications: high current ion beam extraction from plasma sources for ion implantation technology, neutral gas heating in fusion devices, or ion thrusters for space propulsion. One major issue of the development of this code was to improve the flexibility of the applied model for the simulation of different types of particle sources. Fixed emitter sources might be simulated with that code as well as laser ion sources, Penning ion sources, electron cyclotron resonance ion sources (ECRISs), or H(-) sources, which require the simulation of negative ions, negative electrons, and positive charges simultaneously. The model which has been developed for ECRIS has now been used to explore the conditions for the ion beam extraction from a still nonexisting ion source, a so called ARC-ECRIS [P. Suominen and F. Wenander, Rev. Sci. Instrum. 79, 02A305 (2008)]. It has to be shown whether the plasma generator has similar properties like regular ECRIS. However, the emittance of the extracted beam seems to be much better compared to an ECRIS equipped with a hexapole.

Intracellular calcium is an important second messenger that regulates many cell functions. Recent studies have shown that calcium ions can also regulate the cellular responses to ionizing radiation. However, previous data are restricted to cells treated with low-LET radiations (X rays, gamma rays and beta particles). In this work, we investigated the calcium levels in cells exposed to heavy-ion radiation of high LET. The experiments were performed at the single ion hit facility of the GSI heavy-ion microprobe. Using a built-in online calcium imaging system, the intracellular calcium concentrations were examined in HeLa cells and human foreskin fibroblast AG1522-D cells before and after irradiation with 4.8 MeV/nucleon carbon or argon ions. Although the experiment was sensitive enough to detect the calcium response to other known stimuli, no response to heavy-ion radiation was found in these two cell types. We also found that heavy-ion radiation has no impact on calcium oscillation induced by hypoxia stress in fibroblast cells.

Beam profile measurements using viewing targets and emittance measurements with pepper pot devices have established new insights about the ion beam extracted from an electron cyclotron resonance ion source (ECRIS). In our measurements we have compared two different ECRISs of CAPRICE type, one source was equipped with a standard 1.0 T hexapole magnet, whereas for the other ion source a stronger hexapole magnet with a flux density of 1.2 T has been installed. The resulting ion beam profile for each individual charge state produced by different focal strengths of an optical element can be used to estimate the emittance, but it also shows the negative influence of the hexapole on the extracted ion beam. A hexapole correction would be desirable to improve further beam transport. A possible correction scheme will be discussed. All experimental observations can be reproduced by computer simulation if a magnetic plasma is assumed. When the Larmor radius for ions becomes small, collisions are negligible for the path of ions within the plasma. Low energy electrons are highly movable along the magnetic field lines and can compensate the ion space charge within the plasma chamber.

The electron beam ion source MAXEBIS, developed and built at the University of Frankfurt, has been installed at GSI to serve as an offline test ion source for the HITRAP project and for use as a test setup for charge breeding explorations. The setup has been equipped with new diagnostics and beam optics devices. Two ion sources dedicated to the production of singly charged ions for external ion injection into the MAXEBIS have been included. First time of flight (TOF) spectra with external injected, charge-bred argon ions were taken. However, these spectra indicated beam losses in the beam transport from the multipassage spectrometer (MPS) to the MAXEBIS. In order to understand the losses, the beam transport has been simulated with the SIMION code and the beam line has been modified accordingly. Measurements of the MAXEBIS' beam emittance, using the "nondestructive" beam profile method, have been performed as well as measurements of the electron current density via charge state analysis of the TOF spectra. The injection and breeding efficiency of the MAXEBIS have been determined for the first time. The results of the measurements and the planned experiments will be discussed.

High-energy (12)C ions offer favourable conditions for the treatment of deep-seated local tumours. Several facilities for the heavy ion therapy are planned or under construction, for example the new clinical ion-therapy unit HIT at the Radiological University Clinics in Heidelberg. In order to improve existing treatment planning models, it is essential to evaluate the secondary fragment production and to include these contributions to the therapy dose with higher accuracy. Secondary neutrons are most abundantly produced in the reactions between (12)C beams and tissues. The dose contribution to tissues by a neutron is fairly small compared with the projectile and the other charged fragments due to no ionisation and the small reaction cross-sections; however, it distributes in a considerably wider region beyond the bragg-peak because of the strong penetrability. Systematic data on energy spectra and doses of secondary neutrons produced by (12)C beams using water targets of different thicknesses for various detection angles have therefore been measured in this study at GSI Darmstadt.

Systematic nonlinear space-charge resonances may cause substantial emittance growth in the nonscaling fixed-field alternating-gradient (FFAG) accelerators. To avoid systematic nonlinear space-charge resonances, the phase advance of each nonscaling FFAG cell must avoid pi/2 and pi/3. Using multiparticle numerical simulations, we empirically obtain a minimum tune ramp rate vs the systematic 4th order space-charge resonance strength. We also find that the emittance growth obeys a simple scaling property when the betatron tunes cross the linear half-integer and sum resonances.

The FRS-ESR facility at GSI provides unique conditions for precision measurements of large areas on the nuclear mass surface in a single experiment. Values for masses of 604 neutron-deficient nuclides (30 < or = Z < or = 92) were obtained with a typical uncertainty of 30 microu. The masses of 114 nuclides were determined for the first time. The odd-even staggering (OES) of nuclear masses was systematically investigated for isotopic chains between the proton shell closures at Z = 50 and Z = 82. The results were compared with predictions of modern nuclear models. The comparison revealed that the measured trend of OES is not reproduced by the theories fitted to masses only. The spectral pairing gaps extracted from models adjusted to both masses, and density related observables of nuclei agree better with the experimental data.

We show that pronounced collective nonlinear behavior is present in a beam with linear coupling and space charge as described by the complete second order moment equations. The collective effects result in a shifted and broadened resonance condition as well as saturation effects in the emittance transfer. For slow stop-band crossing either the beam evolves along a skewed matched solution with full emittance exchange or the exchange is hindered by collective space charge effects, depending on the emittance ratio and direction of crossing.

Atomic Force Microscopy of phiX174 plasmids irradiated in vitro was used to visualise the DNA fragmentation induced by heavy ions and to compare it to the fragmentation pattern obtained after X-irradiation. Fragment distributions induced by low ion fuences were found to be much more shifted towards small fragment sizes than the distributions obtained after corresponding doses of X-rays. The average fragment length was found to be significantly smaller than the full plasmid length even for single ion traversals.

The mass of one of the three major waiting points in the astrophysical rp process 72Kr was measured for the first time with the Penning trap mass spectrometer ISOLTRAP. The measurement yielded a relative mass uncertainty of deltam/m=1.2x10(-7) (deltam=8 keV). (73,74)Kr, also needed for astrophysical calculations, were measured with more than 1 order of magnitude improved accuracy. We use the ISOLTRAP masses of 72-74Kr to reanalyze the role of 72Kr (T(1/2)=17.2 s) in the rp process during x-ray bursts and conclude that 72Kr is a strong waiting point delaying the burst duration with at least 80% of its beta-decay half-life.

We derive four rigorous conditions for the stability of Coulomb strings in circular storage rings. These criteria are well met by the existing data from experiments in SIS, ESR, and CRYring but not by the NAP-M experiment. We calculate the potential of the joint transverse zigzag excitation and the longitudinal motion against each other of a string of charged particles as a function of their amplitudes and with the linear density as parameter. This potential exhibits a saddle point in amplitude space which, if overcome, destroys the order of the string. The conditions of stability are derived from the position and height of the saddle point which are fairly independent of the linear density. Our findings confirm the supposition that only the Coulomb interaction in the immediate vicinity of very close encounters of particles is important for the existence of strings.

Order-of-magnitude anomalously high intensities for two-electron (dielectronic) satellite transitions, originating from the He-like 2s(2) 1S0 and Li-like 1s2s(2) (2)S(1/2) autoionizing states of silicon, have been observed in dense laser-produced plasmas at different laboratories. Spatially resolved, high-resolution spectra and plasma images show that these effects are correlated with an intense emission of the He-like 1s3p 1P-1s(2) 1S lines, as well as the K(alpha) lines. A time-dependent, collisional-radiative model, allowing for non-Maxwellian electron-energy distributions, has been developed for the determination of the relevant nonequilibrium level populations of the silicon ions, and a detailed analysis of the experimental data has been carried out. Taking into account electron density and temperature variations, plasma optical-depth effects, and hot-electron distributions, the spectral simulations are found to be not in agreement with the observations. We propose that highly stripped target ions (e.g., bare nuclei or H-like 1s ground-state ions) are transported into the dense, cold plasma (predominantly consisting of L- and M-shell ions) near the target surface and undergo single- and double-electron charge-transfer processes. The spectral simulations indicate that, in dense and optically thick plasmas, these charge-transfer processes may lead to an enhancement of the intensities of the two-electron transitions by up to a factor of 10 relative to those of the other emission lines, in agreement with the spectral observations.

We study halo emittance growth in anisotropic beams and show that the rms emittance growth resulting from mismatch is highly anisotropic, depending on the tune ratio. We find that the free-energy limit calculated by Reiser [J. Appl. Phys. 70, 1919 (1991)] for an axisymmetric 1D halo can be extended to 2D if understood as an upper bound to the rms emittance growth averaged per degree of freedom. The thus-obtained "free-energy limit" of an ideal transport system is compared with the halo rms emittance growth in simulations of the Spallation Neutron Source linac.

Space charge can lead to emittance and/or energy exchange known as "equipartitioning issue" in linacs, or space-charge coupling in high-current synchrotrons. It is described here as an internal resonance driven by the self-consistent space-charge potential of coherent eigenmodes. By a detailed comparison of analytical theory with 2D particle-in-cell simulation for Kapchinskij-Vladimirskij (KV) and waterbag distributions, we discuss characteristic features of this resonance mechanism in the vicinity of the symmetric focusing resonance band--for practical purposes, the most important case--and discuss the applicability of the linearized KV theory.

We explain that the anomalous frequency shifts of very close masses obtained in the high precision mass measurement experiments in the ESR storage ring result from the locking of Coulomb interacting strings of ions. Here two concentric strings which run horizontally close to each other are captured into a single string if their thermal clouds overlap and give up their identity.

Energy exchange between the longitudinal and transverse degrees of freedom of nonequipartitioned bunched beams (non-neutral plasmas) is investigated by means of 3D simulation. It is found that collective instability may lead to energy transfer in the direction of equipartition, without full progression to it, in certain bounded regions of parameter space where internal resonance conditions are satisfied, in good agreement with stability charts from an earlier derived 2D Vlasov analysis. Nonequipartitioned stable equilibria, however, exist in relatively wide regimes of parameter space. This provides evidence that such regimes may be safely used in the design of future high-intensity linacs.