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Radiological emergencies involving an accidental or deliberate dispersion of alpha-emitting radionuclides in the environment can cause significant damage to humans and societies in general. Currently, there is a metrology gap in managing such emergencies due to the lack of detectors that can measure alpha particles at distances greater than their range in air: most conventional alpha detectors are only effective when placed just a few centimeters above the contaminated area. This paper presents the development and testing of lens based optical detection systems that utilize alpha particle-induced ultraviolet (UV) luminescence of air, known as alpha radioluminescence. Telescopes based on fused silica and Poly(methyl 2-methylpropenoate) (PMMA) Fresnel lenses were investigated for their usability in facilitating emergency management related to alpha-emitting radionuclides. Careful matching of the diameter and focal length of the receiving optics, the response of the photocathode, and the passband of the filter allows detection sensitivities as high as 34s−1MBq−1 at 2m source-to-detector distance and background count rate of about 3s−1 in the UV-C spectral region, and suppression of daylight background count rate down to 16s−1. By flushing the source with nitrogen (N2) containing trace amounts of nitric oxide (NO), a groundbreaking sensitivity of 1.3×105s−1MBq−1 has been achieved, allowing detection limits as low as 100Bq with room lighting on, and 70Bq in a dark environment. In the UV-A spectral region, a detection limit of 4kBq could be achieved in a dark environment. These optical detection systems are aimed to facilitate a rapid, coordinated, and effective response in emergency situations involving the release of alpha-emitting radionuclides by mounting them on a tripod or an unmanned aerial device (UAV). publishedVersion

In the case of a radiological or nuclear event, biological dosimetry can be an important tool to support clinical decision-making. During a nuclear event, individuals might be exposed to a mixed field of neutrons and photons. The composition of the field and the neutron energy spectrum influence the degree of damage to the chromosomes. During the transatlantic BALANCE project, an exposure similar to a Hiroshima-like device at a distance of 1.5 km from the epicenter was simulated and biological dosimetry based on dicentric chromosomes was performed to evaluate the participants ability to discover unknown doses and to test the influence of differences in neutron spectra. In a first step, calibration curves were established by irradiating blood samples with 5 doses in the range of 0 Gy to 4 Gy at two different facilities in Germany (PTB) and USA (CINF). The samples were sent to eight participating laboratories from the RENEB network and dicentric chromosomes were scored by each participant. Next, blood samples were irradiated with 4 blind doses in each of the two facilities and sent to the participants to provide dose estimates based on the established calibration curves. Manual and semi-automatic scoring of dicentric chromosomes were evaluated for their applicability to neutron exposures. Moreover, the biological effectiveness of the neutrons from the two irradiation facilities was compared. The calibration curves from samples irradiated at CINF showed a 1.4 times higher biological effectiveness compared to samples irradiated at PTB. For manual scoring of dicentric chromosomes, the doses of the test samples were mostly successfully resolved based on the calibration curves established during the project. For semi-automatic scoring, the dose estimation for the test samples was less successful. Doses >2 Gy in the calibration curves revealed non-linear associations between dose and dispersion index of the dicentric counts, especially for manual scoring. The differences in the biological effectiveness between the irradiation facilities suggested that the neutron energy spectrum can have a strong impact on the dicentric counts.

In recent years, several approaches have been proposed to provide an understanding of the enhanced relative biological effectiveness of ion beams based on multi-scale models of their radiation effects. Among these, the BioQuaRT project was the only one which focused on developing metrology for a multi-scale characterization of particle track structure. The progress made within the BioQuaRT project has motivated the formation of a department 'Radiation Effects' at PTB dedicated to metrological research on ionizing radiation effects. This paper gives an overview of the department's present research directions and shortly discusses ideas for the future development of metrology related to biological effects of ion beams that are based on a stakeholder consultation.

PURPOSE The magnetic-field correction factors kB,Q of compact air-filled ionization chambers have been investigated experimentally and using Monte Carlo simulations up to 1.5 T. The role of the nonsensitive region within the air cavity and influence of the chamber construction on its dose response have been elucidated. MATERIALS AND METHODS The PTW Semiflex 3D 31021, PinPoint 3D 31022, and Sun Nuclear Cooperation SNC125c chambers were studied. The kB,Q factors were measured at the experimental facility of the German National Metrology Institute (PTB) up to 1.4 T using a 6 MV photon beam. The chambers were positioned with the chamber axis perpendicular to the beam axis (radial); and parallel to the beam axis (axial). In both cases, the magnetic field was directed perpendicular to both the beam axis and chamber axis. Additionally, the sensitive volumes of these chambers have been experimentally determined using a focused proton microbeam and finite element method. Beside the simulations of kB,Q factors, detailed Monte Carlo technique has been applied to analyse the secondary electron fluence within the air cavity, that is, the number of secondary electrons and the average path length as a function of the magnetic field strength. RESULTS A nonsensitive volume within the air cavity adjacent to the chamber stem for the PTW chambers has been identified from the microbeam measurements and FEM calculations. The dose response of the three investigated ionization chambers does not deviate by more than 4% from the field-free case within the range of magnetic fields studied in this work for both the radial and axial orientations. The simulated kB,Q for the fully guarded PTW chambers deviate by up to 6% if their sensitive volumes are not correctly considered during the simulations. After the implementation of the sensitive volume derived from the microbeam measurements, an agreement of better than 1% between the experimental and Monte Carlo kB,Q factors for all three chambers can be achieved. Detailed analysis reveals that the stem of the PTW chambers could give rise to a shielding effect reducing the number of secondary electrons entering the air cavity in the presence of magnetic field. However, the magnetic field dependence of their path length within the air cavity is shown to be weaker than for the SNC125c chamber, where the length of the air cavity is larger than its diameter. For this chamber it is shown that the number of electrons and their path lengths in the cavity depend stronger on the magnetic field. DISCUSSION AND CONCLUSION For clinical measurements up to 1.5 T, the required kB,Q corrections of the three chambers could be kept within 3% in both the investigated chamber orientations. The results reiterate the importance of considering the sensitive volume of fully guarded chambers, even for the investigated compact chambers, in the Monte Carlo simulations of chamber response in magnetic field. The resulting magnetic field-dependent dose response has been demonstrated to depend on the chamber construction, such as the ratio between length and the diameter of the air cavity as well as the design of the chamber stem.

Background: Most of the heavier $p$ isotopes are believed to be produced in the $\ensuremath{\gamma}$ process whose reaction path crucially depends on the proton and $\ensuremath{\alpha}$-particle penetrability at sub-Coulomb energies. Both nuclei of the samarium $p$-process chronometer, $^{146}\mathrm{Sm}$ and $^{144}\mathrm{Sm}$, are produced in the $\ensuremath{\gamma}$ process, and their initial abundance ratio is very sensitive to the $(\ensuremath{\gamma},n)$ and $(\ensuremath{\gamma},\ensuremath{\alpha})$ branching ratio on $^{148}\mathrm{Gd}$. The $^{148}\mathrm{Gd}(\ensuremath{\gamma},\ensuremath{\alpha})^{144}\mathrm{Sm}$ reaction rate was measured roughly 20 years ago by means of the activation technique and its surprising results triggered adjustments to the global low-energy $\ensuremath{\alpha}+\text{nucleus}$ optical-model potentials (OMPs).Purpose: We want to take advantage of modern $\ensuremath{\alpha}$-particle spectroscopy techniques in order to constrain the controversial previous results on the $^{148}\mathrm{Gd}(\ensuremath{\gamma},\ensuremath{\alpha})^{144}\mathrm{Sm}$ reaction rate.Method: The $^{148}\mathrm{Gd}(\ensuremath{\gamma},\ensuremath{\alpha})^{144}\mathrm{Sm}$ reaction rate has been determined by measuring the cross section of the reverse reaction $^{144}\mathrm{Sm}(\ensuremath{\alpha},\ensuremath{\gamma})^{148}\mathrm{Gd}$, applying the activation technique to the $\ensuremath{\alpha}$ decay of $^{148}\mathrm{Gd}$. Targets have been irradiated at the cyclotron of the Physikalisch-Technische Bundesanstalt in Braunschweig, Germany. The $\ensuremath{\alpha}$-particle spectroscopy has been carried out with a state-of-the-art low-background ionization chamber of the Technische Universit\"at Dresden, Germany.Results: Cross sections for the $^{144}\mathrm{Sm}(\ensuremath{\alpha},\ensuremath{\gamma})^{148}\mathrm{Gd}$ reaction have been measured between 10.66 and 12.66 MeV with much higher precision than in the previous measurement. The results agree with earlier results within their uncertainties. The statistical-model analysis has been carried out using the talys code on the basis of the latest parametrizations of $\ensuremath{\alpha}$-OMPs. The best reproductions of the experimental results within the statistical model have been used to calculate the reaction rates.Conclusion: The values presented here suggest a steeper increase in the astrophysical $S$ factor towards lower center-of-mass energies. Different parametrizations of the $\ensuremath{\alpha}$-OMP were able to describe the experimental values sufficiently. Further measurements at energies below 11.0 MeV are suggested.

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

There is a continued need for further clarification of various aspects of radiation-induced chromosomal aberration, including its correlation with radiation track structure. As part of the EMRP joint research project, Biologically Weighted Quantities in Radiotherapy (BioQuaRT), we performed experimental and theoretical analyses on chromosomal aberrations in Chinese hamster ovary cells (CHO-K1) exposed to α particles with final energies of 5.5 and 17.8 MeV (absorbed doses: ∼2.3 Gy and ∼1.9 Gy, respectively), which were generated by the microbeam at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. In line with the differences in linear energy transfer (approximately 85 keV/μm for 5.5 MeV and 36 keV/μm for 17.8 MeV α particles), the 5.5 MeV α particles were more effective than the 17.8 MeV α particles, both in terms of the percentage of aberrant cells (57% vs. 33%) and aberration frequency. The yield of total aberrations increased by a factor of ∼2, although the increase in dicentrics plus centric rings was less pronounced than in acentric fragments. The experimental data were compared with Monte Carlo simulations based on the BIophysical ANalysis of Cell death and chromosomal Aberrations model (BIANCA). This comparison allowed interpretation of the results in terms of critical DNA damage [cluster lesions (CLs)]. More specifically, the higher aberration yields observed for the 5.5 MeV α particles were explained by taking into account that, although the nucleus was traversed by fewer particles (nominally, 11 vs. 25), each particle was much more effective (by a factor of ∼3) at inducing CLs. This led to an increased yield of CLs per cell (by a factor of ∼1.4), consistent with the increased yield of total aberrations observed in the experiments.

Advances in accelerator technology, which have enabled conforming radiotherapy with charged hadronic species, have brought benefits as well as potential new risks to patients. To better understand the effects of ionizing radiation on tumor and surrounding tissue, it is important to investigate and quantify the relationship between energy deposition at the nanometric scale and the initial biological events. Monte Carlo track structure simulation codes provide a powerful tool for investigating this relationship; however, their success and reliability are dependent on their improvement and development accordingly to the dedicated biological data to which they are challenged. For this aim, a microbeam facility that allows for fluence control, down to one ion per cell nucleus, was used to evaluate relative frequencies of DNA damage after interaction between the incoming ion and DNA according to radiation quality. Primary human cells were exposed to alpha particles of three different energies with respective linear energy transfers (LETs) of approximately 36, 85 or 170 keV·µm-1 at the cells' center position, or to protons (19 keV·µm-1). Statistical evaluation of nuclear foci formation (53BP1/γ-H2AX), observed using immunofluorescence and related to a particle traversal, was undertaken in a large population of cell nuclei. The biological results were adjusted to consider the factors that drive the experimental uncertainties, then challenged with results using Geant4-DNA code modeling of the ionizing particle interactions on a virtual phantom of the cell nucleus with the same mean geometry and DNA density as the cells used in our experiments. Both results showed an increase of relative frequencies of foci (or simulated DNA damage) in cell nuclei as a function of increasing LET of the traversing particles, reaching a quasi-plateau when the LET exceeded 80-90 keV·µm-1. For the LET of an alpha particle ranging from 80-90 to 170 keV·µm-1, 10-30% of the particle hits did not lead to DNA damage inducing 53BP1 or γ-H2AX foci formation.

Since p isotopes cannot be produced in neutron-capture reaction networks, a production mechanism via photodisintegration reactions was proposed - the γ process. The specifc path of this reaction network, however, depends strongly on the statistically averaged ratios for proton-, neutron-, and α-decay widths. It was shown in the past, that the uncertainties in the α-decay widths have an impact on the isotopic abundance of the γ-process ashes. Besides systematic studies of the α+nucleus optical-model potential, direct measurements of (α, γ) reaction are needed to reduce the unpredictability of (γ, α) reaction rates. We present preliminary results from direct measurements of the 98Ru(α,γ) and 144Sm(α,γ) cross sections via in-beam measurements at the University of Cologne and the Ruhr-Universität Bochum and activation experiments at the Physikalisch-Technische Bundesanstalt in Braunschweig and the Technische Universität Dresden. The in-beam experiment might help to improve our understanding of the γ-process contribution to the p nuclei in the A ∼ 100 mass region, while the activation experiment is important for the determination of the initial isotopic abundance ratio of the 146Sm/144Sm chronometer.

Progress in the field of ionising radiation (IR) metrology achieved in the BioQuaRT project raised the question to what extent radiobiological investigations would benefit from metrological support of the applied methodologies. A panel of experts from the medical field, fundamental research and radiation protection attended a workshop at Physikalisch-Technische Bundesanstalt to consult on metrology needs related to biological radiation effects. The panel identified a number of metrological needs including the further development of experimental and computational techniques for micro- and nanodosimetry, together with the determination of related fundamental material properties and the establishment of rigorous uncertainty budgets. In addition to this, a call to develop a metrology support for assisting quality assurance of radiobiology experiments was expressed. Conclusions from the workshop were presented at several international conferences for further discussion with the scientific community and stakeholder groups that led to an initiative within the metrology community to establish a European Metrology Network on biological effects of IR.

Purpose: Radiotherapy for head and neck cancer may result in serious side effects, such as hyposalivation, impairing the patient's quality of life. Modern radiotherapy techniques attempt to reduce the dose to salivary glands, which, however, results in low-dose irradiation of the tissue stem cells. Here we assess the low-dose sensitivity of tissue stem cells and the consequences for tissue function. Experimental Design: Postirradiation rat salivary gland secretory function was determined after pilocarpine induction. Murine and patient-derived salivary gland and thyroid gland organoids were irradiated and clonogenic survival was assessed. The DNA damage response (DDR) was analyzed in organoids and modulated using different radiation modalities, chemical inhibition, and genetic modification. Results: Relative low-dose irradiation to the high-density stem cell region of rat salivary gland disproportionally impaired function. Hyper-radiosensitivity at doses Conclusions: We show that murine and human glandular tissue stem cells exhibit a dose threshold in DDR activation, resulting in low-dose hyper-radiosensitivity, with clinical implications in radiotherapy treatment planning. Furthermore, our results from patient-derived organoids highlight the potential of organoids to study normal tissue responses to radiation.

Gene expression analysis was carried out in Jurkat cells in order to identify candidate genes showing significant gene expression alterations allowing robust discrimination of the Auger emitter $^{123}$I, incorporated into the DNA as $^{123}$I-iododeoxyuridine ($^{123}$IUdR), from α- and γ-radiation. The γ-H2AX foci assay was used to determine equi-effect doses or activity, and gene expression analysis was carried out at similar levels of foci induction. Comparative gene expression analysis was performed employing whole human genome DNA microarrays. Candidate genes had to show significant expression changes and no altered gene regulation or opposite regulation after exposure to the radiation quality to be compared. The gene expression of all candidate genes was validated by quantitative real-time PCR. The functional categorization of significantly deregulated genes revealed that chromatin organization and apoptosis were generally affected. After exposure to $^{123}$IUdR, α-particles and γ-rays, at equi-effect doses/activity, 155, 316 and 982 genes were exclusively regulated, respectively. Applying the stringent requirements for candidate genes, four (PPP1R14C, TNFAIP8L1, DNAJC1 and PRTFDC1), one (KLF10) and one (TNFAIP8L1) gene(s) were identified, respectively allowing reliable discrimination between γ- and $^{123}$IUdR exposure, γ- and α-radiation, and α- and 123IUdR exposure, respectively. The Auger emitter $^{123}$I induced specific gene expression patterns in Jurkat cells when compared with γ- and α-irradiation, suggesting a unique cellular response after $^{123}$IUdR exposure. Gene expression analysis might be an effective tool for identifying biomarkers for discriminating different radiation qualities and, furthermore, might help to explain the varying biological effectiveness at the mechanistic level.

We present predictions of neutron relative biological effectiveness (RBE) for cell irradiations with neutron beams at PTB-Braunschweig. A neutron RBE model is adopted to evaluate initial DNA damage induction given the neutron-induced charged particle field. RBE values are predicted for cell exposures to quasi-monoenergetic beams (0.56 MeV, 1.2 MeV) and to a broad energy distribution neutron field with dose-averaged energy of 5.75 MeV. Results are compared to what obtained with our RBE predictions for neutrons at similar energies, when a 30-cm sphere is irradiated in an isotropic neutron field. RBE values for experimental conditions are higher for the lowest neutron energies, because, as expected, target geometry determines the weight of the low-effectiveness photon component of the neutron dose. These results highlight the importance of characterizing neutron fields in terms of physical interactions, to fully understand neutron-induced biological effects, contributing to risk estimation and to the improvement of radiation protection standards.

The ability of DNA to conduct electric current has been the topic of numerous investigations over the past few decades. Those investigations indicate that this ability is dependent on the molecular structure of the DNA. Radiation-induced damages, which lead to an alteration of the molecular structure, should therefore change the electrical impedance of a DNA molecule. In this paper, the damage due to ionising radiation is shown to have a direct effect on the electrical transport properties of DNA. Impedance measurements of DNA samples were carried out by an AC impedance spectrometer before, during and after irradiation. The samples comprised of DNA segments, which were immobilized between gold electrodes with a gap of 12 μm. The impedance of all DNA samples exhibited rising capacitive behaviour with increasing absorbed dose.

The aim of the 'BioQuaRT' (Biologically weighted Quantities in RadioTherapy) project is to develop measurement techniques for characterising charged particle track structure on different length scales, and to correlate at the cellular level the track structure properties with the biological effects of radiation. This multi-scale approach will allow characterisation of the radiation qualities used in radiotherapy and the related biological effects. Charged-particle microbeam facilities were chosen as the platforms for all radiobiology experiments in the 'BioQuaRT' project, because they allow targeting single cells (or compartments of a cell) with a predefined number of ionising particles and correlating the cell-by-cell induced damage with type and energy of the radiation and with the number of ions per cell. Within this project, a novel in situ protocol was developed for the analysis of the misrepaired and/or unrepaired chromosome damage induced by charged-particle irradiations at the Physikalisch-Technische Bundesanstalt (PTB) ion microbeam facility. Among the cytogenetic biomarkers to detect and estimate radiation-induced DNA damage in radiobiology, chromosomal aberrations and micronuclei were chosen. The characteristics of the PTB irradiation system required the design of a special in situ assay: specific irradiation dishes with a base made from a biofoil 25-μm thick and only 3000-4000 cells seeded and irradiated per dish. This method was developed on Chinese hamster ovary (CHO) cells, one of the most commonly used cell lines in radiobiology in vitro experiments. The present protocol allows the simultaneous scoring of chromosome aberrations and micronuclei on the same irradiated dish. Thanks to its versatility, this method could also be extended to other radiobiological applications besides the single-ion microbeam irradiations. © The Author 2015.

Cross sections for the Yb 168 ( α , γ ) Hf 172 and Yb 168 ( α , n ) Hf 171 reactions were measured by means of the activation method using α particles with energies between 12.9 MeV and 15.1 MeV. The spectroscopy of the γ rays emitted by the reaction products was performed using three different HPGe detector types, namely clover-type high-purity germanium detectors, a low-energy photon spectrometer detector, and a coaxial high-purity germanium detector. The results were compared to Hauser–Feshbach statistical model calculations. Within certain assumptions, astrophysical conclusions could be drawn concerning the production of the p nucleus Yb 168 . The data in this work can serve as a contribution to the current very fragmentary experimental data base for charged-particle induced reactions. In addition, the absolute intensity for nine γ-ray transitions following the electron capture decay of Hf 171 could be derived.

Direct on-chip pulse shape measurements of single-event transients (SETs) in a single inverter in 90-nm bulk CMOS have been performed at the microbeam facility at the Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Germany. Alpha particles with an energy of 8 MeV were used as projectiles, and the supply voltage dependence of the arising SETs was investigated. A strong dependence of the resulting pulse heights, widths, and shapes on the supply voltage could be observed.

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The ambient dose equivalent from the secondary radiation produced during irradiation of a cylindrical water phantom with 200 MeV/u (12)C-ions was investigated at the biophysics cave at GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. Pencil-like ion beams were delivered by the heavy-ion synchrotron SIS18 using the slow extraction mode. Since the secondary radiation field outside the phantom is complex in its particle composition and particle energy distribution, microdosimetric methods developed for the dosimetry of the cosmic radiation field at flight altitudes, which is similar in terms of complexity, were applied. Lineal energy distributions and the ambient dose equivalent were measured with a tissue-equivalent proportional counter at different particle emission angles. An additional veto counter allowed the identification of the different contributions of charged and neutral particles. A significant increase in the mean quality factor was observed at large emission angles which could be attributed to the decreasing contributions of charged particles compared to the (relative) contributions from neutrons.

The production cross sections of 77,79Kr and 77Br following the α-irradiation of natural selenium were determined between the α-energies of 11 MeV and 15 MeV using the activation technique. The irradiation of natural selenium targets with He2+ ions extracted from a cyclotron was conducted at Physikalisch-Technische Bundesanstalt in Braunschweig in Germany. The spectroscopic analysis of the reaction products was performed using a HPGe detector. As the α-beam was stopped inside the targets, the thick target yields were determined. The corresponding energy-dependent cross sections were calculated from the difference of the thick target yields at various beam energies. The determined values were compared to theoretical predictions based on the TALYS code.

Within the next decades, an increasing number of human beings will be brought into space to carry out technical and scientific tasks. There, they will be exposed simultaneously to combined stimuli, especially microgravity and radiation. In the endeavour to assess the risks for humans during long-duration space missions, it is necessary to understand already at the cellular level the complex interplay of these parameters. Cellular stress protection responses lead to an increased transcription of several genes via the modulation of transcription factors. The activation of the nuclear factor κB (NF-κB) pathway as a possible anti-apoptotic route represents such an important cellular stress response. It is hypothesized that the activation of NF-κB and the subsequent expression of NF-κB-dependent genes is involved in the cellular response to components of the cosmic radiation. Irradiation of human embryonic kidney cells (HEK/293) with α-particles (2.1 MeV, LET ∼160 keV/μm) was performed at the PTB, Braunschweig, Germany. Using the microbeam facility, cells were exposed to nuclear hits or, for the purpose of comparison, to a diffuse irradiation of the whole cell. After irradiation the following biological endpoints were determined: (i) cell survival (by means of the colony forming ability test), and (ii) quantitative RT-PCR analysis of selected NF-κB target genes (IκBα GADD45β, bcl-2, and bcl-XL). One nuclear α-particle traversal reduces the probability to survive to ∼75%. Exposure to two α-particles per nucleus resulted in an upregulation of the expression of the GADD45β gene. After exposure of HEK cells to five nuclear hits, about 43% of the irradiated cells survived, and the transcriptional response was not significant. Ten nuclear hits activated the IκBα expression, this increased IκBα production might be involved in the termination of the radiation-induced NF-κB activation. Diffuse irradiation increased the transcription of IκBα and GADD45β. Expression of the antiapoptotic genes bcl-2 and bcl-XL remained almost unchanged after α-particle irradiation. These findings suggest a role for GADD45β in the cellular radiation response to low fluences, while IκBα is enrolled at higher fluences.

International audience; Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented. © 2015 The Authors.

To investigate the dependence of bystander effects on linear energy transfer (LET) in the low dose region.The single-ion microbeam of the Physikalisch-Technische Bundesanstalt (PTB) was used to irradiate confluent primary human skin fibroblasts. Cells plated on a special irradiation dish were targeted with 10 MeV protons (LET 4.7 keV/microm) and 4.5 MeV a-particles (LET 100 keV/microm). During exposure, the cells were confluent allowing signal transfers through both gap junctions and diffusion.For 10 MeV protons the clonogenic capability was significantly higher after exposure to 70 protons (0.31 Gy) compared with unirradiated cells. For higher doses the survival curve was exponential. Exposure of only 10% of all nuclei resulted in a similar radiation response in the low dose region. For higher doses up to 2.2 Gy no cell killing was observed. For 4.5 MeV alpha-particles an exponential survival curve was obtained. Irradiation of only 10% of all cell nuclei resulted in an survival curve as had been expected in the absence of any bystander effect.The type and extent of bystander effects turned out to be dependent on the particles' LET and are likely to depend also on the cell line used and the techniques applied.

Background: Uncertainties in adopted models of $\text{particle}+\text{nucleu}\mathrm{s}$ optical-model potentials directly influence the accuracy in the theoretical predictions of reaction rates as they are needed for reaction-network calculations in, for instance, $\ensuremath{\gamma}$-process nucleosynthesis. The improvement of the $\ensuremath{\alpha}+\text{nucleu}\mathrm{s}$ optical-model potential is hampered by the lack of experimental data at astrophysically relevant energies especially for heavier nuclei.Purpose: Measuring the $^{187}\mathrm{Re}(\ensuremath{\alpha},n)^{190}\mathrm{Ir}$ reaction cross section at sub-Coulomb energies extends the scarce experimental data available in this mass region and helps understanding the energy dependence of the imaginary part of the $\ensuremath{\alpha}+\text{nucleus}$ optical-model potential at low energies.Method: Applying the activation method, after the irradiation of natural rhenium targets with $\ensuremath{\alpha}$-particle energies of 12.4 to 14.1 MeV, the reaction yield and thus the reaction cross section were determined via $\ensuremath{\gamma}$-ray spectroscopy by using the Cologne Clover Counting Setup and the method of $\ensuremath{\gamma}\ensuremath{\gamma}$ coincidences.Results: Cross-section values at five energies close to the astrophysically relevant energy region were measured. Statistical model calculations revealed discrepancies between the experimental values and predictions based on widely used $\ensuremath{\alpha}$+nucleus optical-model potentials. However, an excellent reproduction of the measured cross-section values could be achieved from calculations based on the so-called Sauerwein--Rauscher $\ensuremath{\alpha}+\text{nucleus}$ optical-model potential.Conclusion: The results obtained indicate that the energy dependence of the imaginary part of the $\ensuremath{\alpha}+\text{nucleus}$ optical-model potential can be described by an exponential decrease. Successful reproductions of measured cross sections at low energies for $\ensuremath{\alpha}$-induced reactions in the mass range $141\ensuremath{\le}A\ensuremath{\le}187$ confirm the global character of the Sauerwein--Rauscher potential.

At the PTB's ion accelerators, a new microbeam facility is now in operation that is capable of delivering single ions, for example, to the nuclei of individual living cells. The wide range of proton and 4He2+ ion energies affords LET-values between 3 and 200 keV/μm. A beam diameter of less than 2 μm outside the vacuum system has been measured and a targeting accuracy of better than 2 μm has been determined. In contrast to other microbeam facilities operated for radiobiological research using mechanical collimators in front of the target to define the beam, the PTB facility utilises beam focusing by quadrupole magnets. The microbeam has a unique ion optical design that incorporates a 90° bending magnet in the beam transport system. This design has the advantage of providing a microbeam basically without scattered particles. Every ion reaching the target is detected by a thin scintillating foil and a photomultiplier tube with efficiency close to 100%. Presently up to 1500 single cells per hour can be automatically irradiated with a chosen number of particles. Procedures and results of first cell irradiations are described as an example.

The production of 77,79,85,85mKr and 77Br via the reaction Se(a, x) was investigated between Ea = 11 and 15 MeV using the activation technique. The irradiation of natural selenium targets on aluminum backings was conducted at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. The spectroscopic analysis of the reaction products was performed using a high-purity germanium detector located at PTB and a low energy photon spectrometer detector at the Goethe University Frankfurt, Germany. Thicktarget yields were determined. The corresponding energy-dependent production cross sections of 77,79,85,85mKr and 77Br were calculated from the thicktarget yields. Good agreement between experimental data and theoretical predictions using the TALYS-1.6 code was found.

The increasing importance of ion beams in cancer therapy and the lack of experimental data for W-values for protons and heavy ions in air require new measurements. A new experimental set-up was developed at PTB and consistent measurements of W-values in argon, nitrogen and air for protons and alpha particles with energies from 0.7 to 3.5 MeV u(-1) at PTB, and for carbon ions between 3.6 and 7.0 MeV u(-1) at GSI were carried out. This publication concentrates on the measurements with protons and alpha particles at PTB. The experimental methods and the determination of corrections for recombination effects, beam-induced background radiation and additional effects are presented.

The quasistellar neutron spectrum for a thermal energy of $kT=25$ keV that can be produced via the ${}^{7}$Li($p,n$)${}^{7}$Be reaction at a proton energy of ${E}_{p}=1912$ keV has been measured using the dedicated setup for the definition of neutron fields at Physikalisch-Technische Bundesanstalt Braunschweig. The results confirm previous work with improved accuracy and resolution. Small variations in proton energy leave the spectrum essentially unchanged. This is illustrated by the example of the ($n,\ensuremath{\gamma}$) cross section of ${}^{197}$Au, where the averaged cross section for the spectrum defined in this work agrees perfectly with the result of a previous measurement.

The shape of the low-energy part of the β-delayed α-particle spectrum of 16N is very sensitive to the α+12C reduced width of the 7.117 MeV subthreshold state of 16O. This state, in turn, dominates the low-energy p-wave capture amplitude of the astrophysically important 12C(α,γ)16O reaction. The α spectrum following the decay of 16N has been measured by producing a low-energy 16N14N+ beam with the TRIUMF isotope separator TISOL, stopping the molecular ions in a foil, and counting the α particles and 12C recoil nuclei in coincidence, in thin surface-barrier detectors. In addition to obtaining the α spectrum, this procedure determines the complete detector response including the low-energy tail. The spectrum, which contains more than 106 events, has been fitted by R- and K-matrix parametrizations which include the measured 12C(α,γ)16O cross section and the measured α+12C elastic scattering phase shifts. The model space appropriate for these parametrizations has been investigated. For SE1(300), the E1 part of the astrophysical S factor for the 12C(α,γ)16O reaction at Ec.m.=300 keV, values of 79±21 and 82±26 keV b have been derived from the R- and K-matrix fits, respectively.

The reaction ${}^{141}$Pr($\ensuremath{\alpha},\phantom{\rule{-0.16em}{0ex}}n$)${}^{144}$Pm was investigated between ${E}_{\ensuremath{\alpha}}=$ 11 MeV and 15 MeV with the activation method using the $\ensuremath{\gamma}\ensuremath{\gamma}$ coincidence method with a segmented clover-type high-purity Germanium (HPGe) detector. Measurements with four other HPGe detectors were additionally made. The comparison proves that the $\ensuremath{\gamma}\ensuremath{\gamma}$ coincidence method is an excellent tool to investigate cross sections down to the microbarn range. The ($\ensuremath{\alpha},\phantom{\rule{-0.16em}{0ex}}n$) reaction at low energy is especially suited to test $\ensuremath{\alpha}+\text{nucleus}$ optical-model potentials for application in the astrophysical $p$ process. The experimentally determined cross sections were compared to Hauser-Feshbach statistical model calculations using different optical potentials and generally an unsatisfactory reproduction of the data was found. A local potential was constructed to improve the description of the data. The consequences of applying the same potential to calculate astrophysical ($\ensuremath{\gamma},\ensuremath{\alpha}$) rates for ${}^{145}$Pm and ${}^{148}$Gd were explored. In summary, the data and further results underline the problems in global predictions of $\ensuremath{\alpha}+\text{nucleus}$ optical potentials at astrophysically relevant energies.

The low-energy part of the beta alpha -decay spectrum of 16N permits the determination of the reduced alpha -width theta alpha 2 of the 7.12 MeV subthreshold state of 16O, which dominates the low-energy p-wave capture amplitude of the astrophysically important reaction 12C( alpha , gamma )16O. In a first run, a total of 7.1*103 alpha particles from the decay of 16N nuclei, selected by the TRIUMF isotope separator. TISOL, have been observed in a 10.6 mu m detector in coincidence with the recoiling 12C nuclei in a second detector, thus removing most sources of low-energy alpha background. These new data show a narrower width for the main alpha peak than previously determined. In addition, there is an indication of the low-energy interference anomaly predicted by several authors. The spectrum obtained can be parameterized in K- and R-matrix calculations, which also include the previously-measured 12C( alpha , gamma )16O cross sections and elastic scattering phase shifts. Results of a data collection run in June with much higher alpha yields will be presented.

In an inter-disciplinary collaboration of Physikalisch-Technische Bundesanstalt (PTB), German Collection of Microorganisms and Cell Cultures (DSMZ) and Heinrich-Heine University, live-cell imaging has been established at the charged-particle microbeam facility of PTB. Candidate genes participating in DNA strand-break repair pathways such as PARP-1, MRE11, MSH2, MDC1 and p53BP1 have been modified to generate fluorescent fusion proteins. Using multi-cistronic expression vectors, stable genomic integration was achieved in HT-1080 fibroblasts. The aim of this study is to characterise and use these highly reliable cell lines for studying initial steps of DNA damage responses and kinetics of repair after microbeam irradiation with high- and low-linear energy transfer (LET) particles in living cells at physiological conditions.

An improved assessment of the biological effects and related risks of low doses of ionizing radiation is currently an important issue in radiation biology. Irradiations using microbeams are particularly well suited for precise and localized dose depositions, whereas recombinant cell lines with fluorescent proteins allow the live observation of radiation-induced foci. Living cells of the fibrosarcoma cell line HT-1080 stably expressing 53BP1 or full-length reconstituted MDC1 fused to Green Fluorescent Protein (GFP) were irradiated with protons and α-particles of linear energy transfers (LETs) of 15 and 75 keV/μm, respectively. Using a microbeam, the irradiations were carried out in line patterns, which facilitated the discrimination between undefined background and radiation-induced foci. As expected, foci formation and respective kinetics from α-particle irradiations with a high LET of 75 keV/μm could be detected in a reliable manner by both fusion proteins, as reported previously. Colocalization of γ-H2AX foci confirmed the DSB nature of the detected foci. As a novel result, the application of protons with low LET of 15 keV/μm generated 53BP1- and MDC1-mediated foci of almost equal size and slightly different kinetics. This new data expands the capability of 53BP1 and wild-type MDC1 on visible foci formation in living cells after irradiation with low-LET particles. Furthermore, the kinetics in HT-1080 cells for α-particle irradiation show a delay of about 20 s for 53BP1 foci detection compared to wild-type MDC1, confirming the hierarchical assembly of both proteins. Preliminary data for proton irradiations are shown and also these indicate a delay for 53BP1 versus MDC1.

A compact and transportable water calorimeter has been developed and extensively tested in the intensive, collimated neutron field of the PTB. It has been applied for absorbed dose to water measurements in the neutron therapy field of the University of Essen, in the proton therapy fields of the HMI in Berlin and at the iThemba therapy centre near Cape Town, South Africa, as well as in the (12)C-beam of the therapy facility at GSI in Darmstadt, Germany. Absolute dosimetry with relative standard uncertainties of less than 1.8% was achieved in all radiation fields. The results obtained using the water calorimeter are compared with the ionisation chamber measurements in the same radiation fields. The heat defect for the water in the calorimeter core was determined separately in independent measurements by irradiation with different charged particle beams covering a wide range of linear energy transfer.

The purpose of this study was to systematically investigate how high doses of sparsely and densely ionizing radiations influence the proliferation time of lymphocytes in short-term cultures and, consequently, the observed frequencies of dicentric and centric ring chromosomes. Peripheral blood samples from five volunteers were irradiated with high doses of 200 kV X-rays and with neutrons with a mean energy ofEnor=2.1 MeV. First division metaphase cells were collected after different culture times of 48, 56, and 72 h and dicentrics, centric ring chromosomes, and acentric fragments were determined. The data hint at considerable mitotic delay. The main increase in the number of chromosome aberrations occurred between 48 and 72 h after an X-ray exposure and between 56 and 72 h after neutron exposure. When the data were used for a calibration of aberration frequency versus dose, subsequent dose estimations resulted, however, in comparable values. Thus, in spite of the influence of mitotic delay on observable chromosome aberrations, at least for the radiation types investigated here, a culture time of 48 h is acceptable for biological dosimetry.

Two experiments were performed to resolve a discrepancy of the 197Au(n, γ) cross section between the IAEA standard evaluation and the reference cross section for astrophysical experiments in the lower keV energy region. We measured the 197Au(n, γ) reaction by means of the time-of-flight technique with n-TOF at CERN and extracted the cross section in the unresolved resonance region between 5-400 keV with an overall uncertainty from 3.9-6.7% for a resolution of 20 bins per energy decade. Additionally, we remeasured the neutron spectrum of the 7Li(p, n) 7Be reaction with E p=1912 keV, which was used as a neutron source for determining the astrophysical reference cross section. The n-TOF data are already fully analyzed and published. The results are in good agreement with the ENDF standard evaluation, but uncertainties don't allow to draw definite conclusions. The analysis of the neutron spectrum of 7Li(p, n) 7Be is underway, preliminary results will be reported here.