Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

Im Falle einer Inkorporation radioaktiver Stoffe entstehen ernsthafte gesundheitliche Risiken durch deren Chemo- und Radiotoxizität. Um die möglichen toxischen Effekte besser abschätzen und letztendlich verhindern zu können, ist es notwendig, die Speziation dieser Elemente im menschlichen Organismus auf molekularer Ebene zu verstehen. Die Speziation beeinflusst die Aufnahme, den Transport, den Metabolismus, die Einlagerung und die Ausscheidung der Elemente.
Die Gefahr einer oralen Aufnahme von Radionukliden besteht durch kontaminierte Lebensmittel oder Trinkwasser. Deshalb haben wir die Speziation von ausgewählten dreiwertigen Actiniden und Lanthaniden (Cm(III) und Eu(III)) in den Biofluiden des Verdauungstraktes näher untersucht. Die Biofluide wurden nach einer international anerkannten Methode (Unified Bioaccessibility Method, UBM) der Bioaccessibility Research Group of Europe (BARGE) synthetisch hergestellt [1]. Parallel dazu wurden natürliche menschliche Speichelproben zum Vergleich in die Untersuchungen einbezogen [2].
Die Speziatonsuntersuchungen von Cm(III) und Eu(III) in den Verdauungsfluiden wurden mit Hilfe der zeitaufgelösten laserinduzierten Fluoreszenzspektroskopie (Time-Resolved Laser-induced Fluorescence Spectroscopy, TRLFS) durchgeführt. Für Speichel wurde ermittelt, dass sich zum größten Teil (60-90%) anorganische Komplexe bilden, darunter dominiert ein ternärer Komplex mit Phosphat und Carbonat als Liganden und Calcium als weiterem Kation zum Ladungsausgleich. Organische Komplexe, hauptsächlich mit dem Verdauungsenzym α-Amylase, wurden ebenfalls nachgewiesen. Wenn die Speichelmischung den Magen erreicht, findet aufgrund des niedrigen pH-Wertes im Magen (pH<2) eine Dissoziation der Komplexe statt, Cm(III) und Eu(III) liegen dann hauptsächlich in Form ihrer Aquo-Komplexe vor. Aber ein kleiner Teil der Metallionen (ca. 20%) bildet trotz des niedrigen pH-Wertes Komplexe mit dem Verdauungsenzym Pepsin. Im Dünndarm, wo die eigentliche Verdauung und die Absorption der (Nähr-, aber auch Gift-)Stoffe in den Blutkreislauf stattfindet, werden die Metallionen hauptsächlich (ca. 65%) von dem Protein Muzin komplexiert, welches Hauptbestandteil der schützenden Schleimhaut (Mucosa) ist, und ca. 35% liegen als anorganische Spezies mit Phosphat und Carbonat als Liganden vor.

Referenzen

[1] J. Wragg et al., British Geological Survey Open Report OR/07/027, Keyworth, Nottingham, 2009, 90 pp.
2] A. Barkleit et al., Dalton Trans. 46, 2017, 1593-1605.

In case of incorporation into the human body, radionuclides potentially represent serious health risks due to their chemo- and radiotoxicity. In order to assess their toxicological behavior, such as transport, metabolism, deposition, and elimination from the human organisms, the understanding of their in vivo chemical speciation on a molecular level is crucial. Nevertheless, little is known about the speciation of not only trivalent actinides (An(III)) but also trivalent lanthanides (Ln(III)), non-radioactive chemical analogs of An(III), in human body fluids. In order to improve our understanding of the behavior of An(III) and Ln(III) in the human body, the present study focuses on the chemical speciation of An(III) and Ln(III) in the gastrointestinal tract. The human gastrointestinal system was simulated by using an in vitro digestion model, part of an international unified bioaccessibility method (UBM), developed by the Bioaccessibility Research Group of Europe (BARGE) (Wragg et al., 2009). To verify the model, natural human saliva samples were also investigated (Barkleit et al., 2017).
The speciation of trivalent curium (Cm(III)) and europium (Eu(III)) in the gastrointestinal tract and in human natural saliva has been studied by means of time-resolved laser-induced fluorescence spectroscopy (TRLFS). The standard model body fluids and the natural saliva samples were spiked in vitro with Cm(III) or Eu(III) with a trace metal concentration.
The dominant chemical species in the body fluids were determined by linear combination fitting (LCF) analysis based on the reference spectra for individual components in the body fluids. The results indicates the formation of inorganic- (60-90%) and organic species (10-40%) of Cm(III)/Eu(III) in the salivary media. Ternary M(III) complexes containing phosphate and carbonate anions with the additional counter-cation calcium is found to be the main inorganic species, while the complexes with the digestive enzyme α-amylase and the protein mucin represent the major part of the organic species.
When the M(III) reached the stomach, the metal complexes are dissociated due to the high acidic conditions in the stomach. That is, Cm(III) and Eu(III) are mainly present as aquo complexes, while a small part (about 20%) is coordinated by the protein pepsin. When entering the intestine the M(III) strongly interact with the protective protein mucin (about 65%) and inorganic ligands (mainly carbonate and phosphate).
These speciation results in different body fluids of the gastrointestinal tract pointed out that An(III) and Ln(III) are coordinated by both inorganic and organic molecules in the human digestive system. Proteins (e.g., α-amylase, pepsin, mucin) would be the important organic binding partners. Furthermore, ternary inorganic complexes containing phosphate and carbonate anions with the additional counter-cation calcium are expected to be formed as the main inorganic species in the whole body fluids.

Wragg, J., Cave, M., Taylor, H., Basta, N., Brandon, E., Casteel, S., Gron, C., Oomen, A., van de Wiele, T., 2009. British Geological Survey Open Report OR/07/027, Keyworth, Nottingham, 90 pp.
Barkleit, A., Wilke, C., Heller, A., Stumpf, T., Ikeda-Ohno, A., 2017. Trivalent f-elements in human saliva: a comprehensive speciation study by time-resolved laser-induced fluorescence spectroscopy and thermodynamic calculations. Dalton Trans. 46, 1593-1605

Ecological problems resulting from the reckless uranium mining in Saxony and Thuringia within approximately 45 years are illustrated, and contributions in determination of these problems by the spectroscopic methods TRFLS and EXAFS are showed.

Ceramic material is under discussion to be an alternative to borosilicate glass for the immobilization of nuclear waste. The corrosion resistance of ceramic material can increase over several magnitudes compared to glass. A homogenous mixture of the actinide and the ceramics precursor is essential to supress phase segregation which may weaken the dissolution resistance under the conditions of a nuclear waste repository. We investigated different sol-gel preparation routes of zirconia (ZrO2) and zircon (ZrSiO4) based ceramics.
Laboratory studies were accompanied by X-ray absorption spectroscopy (XAS) performed at the Rossendorf Beamline (ROBL). The beamline has broadened its experimental capacities with a 6-circle diffractometer which was used in this study for powder X-ray diffraction (XRD) experiments. Among the synthesis attempts, an acetate-base route seems to support the homogeneity of the precursor for zirconia-based ceramics, most likely because An(IV) and Zr(IV) show the same complexes in the sols [1,2]. X-ray absorption spectroscopy reveals that acetate supported An(IV) clusters are structurally very close to the zirconia structure units [3] and remain obviously intact when entering the zirconia ceramics. X-ray powder diffraction measurements show that this synthesis route reduces phase segregation in zirconia ceramics during thermal treatment. The host lattice needs a certain flexibility to tolerate the introduction of An(IV) ions. However, zirconia has a rigid structure which limits the intercalation of An(IV). The synthesis of zircon-based ceramics is faced with the problem that ZrSiO4 has no extended phase range in the ZrO2-SiO2 system and appears therefore in equilibrium with one of the limiting species. However, zircon shows a large structural flexibility. Therefore, zircon-based ceramics can be synthesized in a way that it forms unlimited solid solutions with An(IV).

The paper presents investigation results on the cooling effect of rising steam on heated rods during a loss of cooling accident scenario in a fuel element mock-up in the spent fuel pool. Therefore, the newly developed thermal anemometry grid sensor was used. With the measured time course of gas-phase temperature and velocity in the subchannels the convection cooling of the rods by steam was verified.

The FP7 EURATOM project FREYA has been executed between 2011 and 2016 with the aim of supporting the design of fast lead-cooled reactor systems such as MYRRHA and ALFRED. During the project, a number of critical experiments were conducted in the VENUS-F facility located at SCK•CEN, Mol, Belgium.
The Monte Carlo code Serpent was one of the codes applied for the characterization of the critical VENUS-F cores. Four critical configurations were modeled with Serpent, namely the reference critical core, the clean MYRRHA mock-up, the full MYRRHA mock-up, and the critical core with the ALFRED island.
This paper briefly presents the VENUS-F facility, provides a detailed description of the aforementioned critical VENUS-F cores, and compares the numerical results calculated by Serpent to the available experimental data. The compared parameters include keff, point kinetics parameters, fission rate ratios of important actinides to that of U235 (spectral indices), axial and radial distribution of fission rates, and lead void reactivity effect.
The reported results show generally good agreement between the calculated and experimental values. Nevertheless, the paper also reveals some noteworthy issues requiring further attention. This includes the systematic overprediction of reactivity and systematic underestimation of the U238 to U235 fission rate ratio.

Declining grade of primary ores and resource efficiency have led us to process more alternative metal resources such as e-waste. One of the processing routes for extracting valuable metals from e-waste is through the black copper smelting. However, the underlying knowledge of the thermodynamics behaviour of the valuable metals contained in e-waste during smelting are limited which prevent us from developing an optimised process to recover all the metals. These different metals clearly will have different favourable conditions for their extraction. To illustrate this, the distribution behaviour of germanium (Ge) and palladium (Pd) between liquid copper and ferrous-calcium-silicate slag during black copper smelting was analysed. It was demonstrated that oxygen partial pressure and slag composition affect the partitioning of these metals to the copper phase and the favourable slag chemistry for recovering these metals is opposing. Considering the available thermodynamic data of these metals, an analysis for the optimum conditions is presented.

Introduction: Commonly used clinical models for survival prediction after stereotactic radiosurgery (SRS) for brain metastases (BMs) are limited by the lack of individual risk scores and disproportionate prognostic groups. In this study, two nomograms were developed to overcome these limitations.
Methods: 495 patients with BMs of NSCLC treated with SRS for a limited number of BMs in four Dutch radiation oncology centers were identified and divided in a training cohort (n = 214, patients treated in one hospital) and an external validation cohort n = 281, patients treated in three other hospitals). Using the training cohort, nomograms were developed for prediction of early death (<3 months) and long-term survival (>12 months) with prognostic factors for survival. Accuracy of prediction was defined as the area under the curve (AUC) by receiver operating characteristics analysis for prediction of early death and long term survival. The accuracy of the nomograms was also tested in the external validation cohort.
Results: Prognostic factors for survival were: WHO performance status, presence of extracranial metastases, age, GTV largest BM, and gender. Number of brain metastases and primary tumor control were not prognostic factors for survival. In the external validation cohort, the nomogram predicted early death statistically significantly better (p < 0.05) than the unfavorable groups of the RPA, DS-GPA, GGS, SIR, and Rades 2015 (AUC = 0.70 versus range AUCs = 0.51–0.60 respectively). With an AUC of 0.67, the other nomogram predicted 1 year survival statistically significantly better (p < 0.05) than the favorable groups of four models (range AUCs = 0.57–0.61), except for the SIR (AUC = 0.64, p = 0.34). The models are available on www.predictcancer.org.
Conclusion: The nomograms predicted early death and long-term survival more accurately than commonly used prognostic scores after SRS for a limited number of BMs of NSCLC. Moreover these nomograms enable individualized probability assessment and are easy into use in routine clinical practice.

PIConGPU is currently the fastest particle-in-cell code in the world. New physics models are continuously developed and, after thorough testing, included in our open-source software.

In this talk we will give an overview on the recent upgrades in PIConGPU, covering new ionization schemes including ADK, Keldysh and collisional ionization, a QED and bremsstrahlung module that brings photons to the code, and various new laser implementations to better model lasers used in experiments and to enable the simulation of novel light source concepts like TWTS. We will present various synthetic diagnostic methods such as the spectrally resolved radiation detectors, the in-situ phase space diagnostic and our ParaTAXIS framework, which is able to simulate small angle photon scattering of an external x-ray pulse probing laser-driven solid-density targets. Furthermore, we will briefly discuss numerous code improvements which boost performance, unify data exchange and analysis via the openPMD standard for open, reproducible science, and our steerable live visualization. Finally we will showcase several simulations ranging from laser wakefield acceleration via ionization injection, to ion acceleration via laser interaction with spherical, perfectly isolated, mass-limited targets (both experimentally realized) to radiation signatures of a shear surface instability.

Laser-ion acceleration is a promising concept towards compact high-gradient particle acceleration. Most laser-ion acceleration mechanisms are operating with optically over-dense targets and are sensitive to emerging plasma instabilities, negatively impacting stability, control and beam quality. In order to gain higher control over the acceleration process, upcoming pump-probe experiments at the European XFEL and and adequate modeling in full 3D simulations can be deployed. This poster describes our efforts on integrating SCFLY's collisional-radiative non-LTE model into the electro-magnetic particle-in-cell code PIConGPU.

We demonstrate the conversion of lattice-matched InGaAs/InAlAs quantum-cascade-laser (QCL) active-region material into an effective current-blocking layer via proton implantation. A 35-period active region of an 8.4 μm-emitting QCL structure was implanted with a dose of 5 × 10^14 cm−2 protons at 450 keV to produce a vacancy concentration of ∼10^19 cm−3. At room temperature, the sheet resistance, extracted from the Hall measurements, increases by a factor of ∼240 with respect to that of an unimplanted material. Over the 160–320 K temperature range, the activation energy of the implanted-material Hall sheet-carrier density is 270 meV. The significant increase in room-temperature sheet resistance indicates that upon implantation deep carrier traps have been formed in the InAlAs layers of the superlattice. Fabricated mesas show effective current blocking, at voltages ≥10 V, up to at least 350 K. Thus, the implanted InGaAs/InAlAs superlattices are highly resistive to at least 350 K heat sink temperature. Such implanted material should prove useful for effective current confinement in 8–15 μm-emitting InP-based single-emitter QCL structures as well as in resonant leaky-wave coupled phase-locked arrays of QCLs.

Abstract

The EU-funded research project BIOMOre[1] is designed to develop a new technological concept for the in-situ recovering of copper from deep European Kupferschiefer ore deposits by using controlled stimulation of pre-existing fractures in combination with in-situ bioleaching. The BIOMOre project mainly focuses on the leaching experiments in lab and field scale and the related reactive transport modeling including the required backcoupling from geochemical reactions on the hydrodynamics as well as the upscaling. We here present most recent, preliminary results that focus on reactive transport simulations on a drill core sample in 4D (3D+t). While we still use synthetic porosity and velocity fields, the model is capable of later imported velocity and effective porosity fields obtained from the transport process visualization method, GeoPET. This technique has been established by members of the Reactive Transport Division of the HZDR in the past decade and allows the direct, non-destructive, quantitative spatiotemporal visualization of (reactive) transport processes in natural geological media on drill-core scale [2-6].
A mechanically induced fracture was designed with a geomechanical shear test in a calciferous sandstone drill core sample obtained from the Kupferschiefer ore formation. While the long term leach experiment is still ongoing the pH value and preliminary Ca+ and Cl- contents from the breakthrough are aligned with those from the reactive transport modelling conducted by means of iCP[7] (an interface coupling of the finite element based code COMSOL Multiphysics® with the geochemical code PhreeqC). The model consideres mineral leaching due to the injection of an acidic solution with pH of 1.5 to the fracture. Currently the flow is still simulated by the Forchheimer equation [8] in matrix and fracture. The chemical processes considered in the model are kinetically controlled mineral dissolution and precipitation in the porous media simulated by means of PHREEQC[9] and advective-dispersive transport in the fracture and matrix diffusion in the rock mass calculated by COMSOL Multiphysics. Calcite dissolution and gypsum precipitation were monitored in the results of the model.
Our further tasks in the project will consider more realistic structure geometry of rock core sample (fracture and matrix) and quantified advective distributions obtained from GeoPET.

Non-uniform bubble size and liquid velocity distribution in bubble columns lead to gas phase dispersion. This gas phase backmixing is quantitatively modelled in the axial gas dispersion model by the axial gas dispersion coefficient. However, only few gas phase dispersion data are currently available since experimental investigations are expensive and require the application of suitable gas tracers and their reliable detection. In this study a new approach is introduced, which is based on a lock-in measurement of gas fraction modulation. Experiments were carried out in a bubble column of 100 mm diameter operated with air/water and air/glycol-water, respectively. Gas holdup was measured via gamma-ray densitometry in synchronization with the modulated inlet flow. The axial dispersion model was adopted to determine the gas phase dispersion coefficient from phase shift and amplitude damping of the gas holdup frequency response. A sensitivity analysis was performed to derive a proper modulation scheme. The calculated gas phase dispersion coefficients show excellent agreement with data from literature.

As a consequence of nuclear waste disintegration heat, elevated temperatures in the near field of geological repositories may influence radionuclide retention at interfaces significantly. However, experimental data on free Gibbs energy (ΔRG), enthalpy (ΔRH) and entropy (ΔRS) of reactions of most radionuclides including fission products such as 79Se are sparse. Using the Se(IV)/maghemite system, we intended to show that microcalorimetry can provide these thermodynamic parameters with high accuracy and in a manner that allows studying various radionuclides.
The detection of the heat of the sorption reaction of Se(IV) onto maghemite was accomplished by isothermal titration calorimetry. Experiments were carried out at temperatures ranging from 20 to 40 °C and at pH 5. The heat flow was recorded as a function of time during the titrations (Figure 1).
The adsorption process was found to be exothermic, in agreement with findings of batch experiments. As the number of injections increases, the signal continuously decreases. Indeed, during the course of injections, the binding sites of maghemite are being gradually saturated by Se(IV), and the exothermic effect gets consequently reduced until only the heat of dilution is detected.
The heat (in J) related to each injection can be derived from single peak areas. The sum of all injections represents the corresponding enthalpy of the overall reaction (ΔRH). Additionally, the molar enthalpy of adsorption (J mol−1) can be determined and, thus, the number of adsorbed Se(IV) molecules as well. By applying the Langmuir isotherm, and assuming the proportionality of the maximum adsorption capacitiy qm to the mass to volume ratio, the Langmuir constant (log KL) can be derived.
In the future, spectroscopic techniques evidencing the nature of the adsorption process and the number of relevant species at the surface will be combined with microcalorimetry. Thus, a thermodynamic description of the selenium mobility in natural systems will be assessed with much more confidence and lower uncertainties.

Retrospective evaluation of 188 advanced stage non-small cell lung cancer patients treated with IMRT or VMAT revealed a limited increase of moderate to severe acute esophageal toxicity after VMAT. Acute pulmonary toxicity and severe late toxicity were low. Overall survival did not differ between the IMRT and VMAT groups.

Supplementing the holographic Einstein-Maxwell-dilaton model of [O. DeWolfe, S.S. Gubser, C. Rosen, Phys. Rev. D83 (2011) 086005; O. DeWolfe, S.S. Gubser, C. Rosen, Phys. Rev. D84 (2011) 126014] by input of lattice QCD data for 2+1 flavors and physical quark masses for the equation of state and quark number susceptibility at zero baryo-chemical potential we explore the resulting phase diagram over the temperature-chemical potential plane. A first-order phase transition sets in at a temperature of about 112 MeV and a baryo-chemical potential of 989 MeV. We estimate the accuracy of the critical point position in the order of approximately 5% by considering different low-temperature asymptotics for the second-order quark number susceptibility. The critical pressure as a function of the temperature has a positive slope, i.e. the entropy per baryon jumps up when crossing the phase border line from larger values of temperature/baryo-chemical potential, thus classifying the phase transition as a gas-liquid one. The updated holographic model exhibits in- and outgoing isentropes in the vicinity of the first-order phase transition.

Unnatural mirror image L-configured oligonucleotides (L-ONs) are a convenient substance class for the application as complementary in vivo recognition system between a tumor specific antibody and a smaller radiolabeled effector molecule in pretargeting approaches. The high hybridization velocity and defined melting conditions are excellent preconditions of the L-ON based methodology. Their high metabolic stability and negligible unspecific binding to endogenous targets are superior characteristics in comparison to their D-configured analogs. In this study, a radiopharmacological evaluation of a new L-ONs based pretargeting system using the epidermal growth factor receptor (EGFR) specific antibody cetuximab (C225) as target-seeking component is presented. An optimized PEGylated 17mer-L-DNA was conjugated with p-SCN-Bn-NOTA (NOTA’) to permit radiolabeling with the radionuclide 64Cu. C225 was modified with the complementary 17mer-L-DNA (c-L-DNA) strand as well as with NOTA’ for radiolabeling and use for positron emission tomography (PET). Two C225 conjugates were coupled with 1.5 and 5.0 c-L-DNA molecules, respectively. In vitro characterization was done with respect to hybridization studies, competition and saturation binding assays in EGFR expressing squamous cell carcinoma cell lines A431 and FaDu. The modified C225 derivatives exhibited high binding affinities in the low nanomolar range to the EGFR. PET and biodistribution experiments on FaDu tumor bearing mice with directly 64Cu-labeled NOTA’3-C225-(c-L-DNA)1.5 conjugate revealed that a pretargeting interval of 24 h might be a good compromise between tumor accumulation, internalization, blood background, and liver uptake of the antibody. Despite internalization of the antibody in vivo pretargeting experiments showed an adequate hybridization of 64Cu-radiolabeled NOTA’-L-DNA to the tumor located antibody and a good tumor-to-muscle ratio of about 11 resulting in a clearly visible image of the tumor after 24 h up to 72 h. Furthermore, low accumulation of radioactivity in organs responsible for metabolism and excretion was determined. The presented results indicate a high potential of complementary L-ONs for the pretargeting approach which can also be applied to therapeutic radionuclides such as 177Lu, 90Y, 186Re or 188Re.

In 1996 Sir Harold W. Kroto, Robert F. Curl and Richard E. Smalley were honored with the Nobel Prize in Chemistry for the discovery of fullerenes. The advent of these new forms of carbon heralded a race to understand the physical and chemical properties. C60 is virtually insoluble in polar solvents but is partially soluble in benzene, toluene, and carbon disulfide. This made the processing of fullerenes for new applications fairly problematic. However, the physical and chemical properties of these cage structures may be tailored for a wide range of applications. Some of the difficulties in processing have been overcome by using novel fullerene derivatives. The functionalization of the fullerene core with different chemical moieties provided a vector towards potential applications in drug delivery, optoelectronics, electrochemistry and organic photovoltaics. In this review, we will take a closer look at the features of some of the fullerene derivatives that have reinvigorated the field of fullerene research. Water-soluble polyhydroxylated fullerenes such as fullerenol have demonstrated the potential for good electron transfer and optical transmission, while hydrophobic fullerene derivatives have shown promising avenues for catalytic applications.
2015 marked the 30th anniversary of the discovery of fullerenes, with celebrations around the world including an event by the Royal Society of Chemistry, bringing together many of Sir Harold Kroto’s former students. The event also coincided with the recent discovery of C60+ in space after a complex twenty-year search. It is with sadness that we, Harry’s Research Group at Florida State University, and his international collaborators, reflect on the passing of Sir Harold Kroto. His dedication to science and commitment to science communication through the VEGA Science Trust and the Global Educational Outreach for Science Engineering and Technology (GEOSET) initiative help to raise awareness of the challenges for science in the modern world. We will continue to inspire young students through outreach activities he initiated.

Knowledge of the radionuclide transfer in the environment up to the food chain is the basis for a reliable safety assessment of potential nuclear waste disposal sites as well as for the evaluation of suitable remediation measures for radioactively contaminated areas, e.g., NORM sites. The uptake of radionuclides by plants is often described by transfer factors. To improve the knowledge of the underlying processes, the interactions of plants with radionuclides, e.g., uranium, are investigated on a molecular level (e.g., Günther et al., 2003, Laurette et al., 2012, Geipel and Viehweger, 2015). We studied the interaction of U(VI) with canola cells (Brassica napus) and focused on the concentration-dependent influence of U(VI) on the cell metabolism. Isothermal microcalorimetry was used as an extremely sensitive tool to monitor the metabolic heat flow of the cells in the absence and presence of U(VI). The cell viability was studied using the MTT test (Mosmann, 1983). The speciation of U(VI) in the nutrient medium was determined by time-resolved laser-induced fluorescence spectroscopy (TRLFS) and thermodynamic modeling to correlate the impact of U(VI) on the cell metabolism with its speciation.
Isothermal microcalorimetry is a highly sensitive monitor of the concentration and probably speciation-dependent U(VI) toxicity in plant cells. The metabolic response of the cells correlates very well with their mitochondrial activities. This opens possibilities to distinguish between chemo- and radiotoxic effects of U(VI) in calorimetric experiments.

We proposed prediction methods for countercurrent flow limitation (CCFL) in horizontal and slightly inclined pipes with one-dimensional (1-D) computations and uncertainty of computed CCFL. In this study, we applied the proposed methods to a full-scale pressurizer surge line [inclination angle theta = 0.6 deg, diameter D = 300 mm, and ratio of the length to the diameter (L/D) = 63] in a specific pressurized water reactor, performed 1-D computations and three-dimensional (3-D) numerical simulations, and found that uncertainties caused by effects of the diameter and fluid properties on CCFL were small. We also applied the proposed methods to experiments for hot-leg and surge line models (theta = 0 and 0.6 deg, D = 0.03 to 0.65 m, and L/D = 4.5 to 63) to generalize them, performed 1-D computations, and found that uncertainties caused by effects of theta and L on CCFL were large due to the setting error for theta and differences among experiments. This shows that a small-scale air-water experiment with the same theta and L/D as those in an actual plant is effective to reduce the uncertainty of CCFL prediction.

In this paper we report on the investigation of Δ(1232) production and decay in proton-proton collisions at a kinetic energy of 1.25 GeV measured with HADES. Exclusive dilepton decay channels ppe⁺e^- and ppe⁺e^-γ have been studied and compared with the partial wave analysis of the hadronic ppπ⁰ channel. They allow to access both Δ⁺ -> π⁰(e⁺e^-γ)p and Δ⁺ -> pe⁺e^- Dalitz decay channels. The perfect reconstruction of the well known π⁰ Dalitz decay serves as a proof of the consistency of the analysis. The Δ Dalitz decay is identified for the first time and the sensitivity to N-Δ transition form factors is tested. The Δ(1232) Dalitz decay branching ratio is also determined for the first time; our result is (4.19 +- 0.62 syst. +- 0.34 stat.) x 10^-5, albeit with some model dependence.

Lymph node stage prior to treatment is strongly related to disease progression and poor prognosis in non-small cell lung cancer (NSCLC). However, few studies have investigated metabolic imaging features derived from pre-radiotherapy 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) of metastatic hilar/mediastinal lymph nodes (LNs). We hypothesized that these would provide complementary prognostic information to FDG-PET descriptors to only the primary tumor (tumor).
Methods: Two independent cohorts of 262 and 50 node-positive NSCLC patients were used for model development and validation. Image features (i.e. Radiomics) including shape and size, first order statistics, texture, and intensity-volume histograms (IVH) (www.radiomics.org) were evaluated by univariable Cox regression on the development cohort. Prognostic modelling was conducted with a 10-fold cross-validated least absolute shrinkage and selection operator (LASSO), automatically selecting amongst FDG-PET-Radiomics descriptors from (1) tumor, (2) LNs or (3) both structures. Performance was assessed with the concordance-index. Development data are publicly available at www.cancerdata.org.
Results: Common SUV descriptors (maximum, peak, and mean) were significantly related to overall survival when extracted from LNs, as were LN volume and tumor load (summed tumor and LNs’ volumes), though this was not true for either SUV metrics or tumor’s volume. Feature selection exclusively from imaging information based on FDG-PET-Radiomics, exhibited performances of (1) 0.53 – external 0.54, when derived from the tumor, (2) 0.62 – external 0.56 from LNs, and (3) 0.62 – external 0.59 from both structures, including at least one feature from each sub-category, except IVH.
Conclusion: Combining imaging information based on FDG-PET-Radiomics features from tumors and LNs is desirable to achieve a higher prognostic discriminative power for NSCLC.

3D cell cultures appear in many different self-made and commercially available facets. A common denominator for some of them is that they enable cell growth in a more physiological environment than conventional 2D cell cultures. Unfortunately, validation of their suitability to do so and to fit to a particular scientific question is mostly missing. In this teaching lecture I will discuss validation strategies and data of comparative analyses between 2D, 3D and tumor xenografts of various processes such as signal transduction, DNA repair and others. Based on our long-standing experience, a large variety of endpoints can be determined and many methods can be conducted in 3D cell cultures. While this is sometimes not as easy as in 2D and also requires a bit more financial invest, the generated data reflect cell behavior in-vivo and thus have a higher clinically relevance. Further, we are able to address specific tumor features in detail. For example, malignant tumors show great genetic/epigenetic and morphological/cell biological heterogeneity. Another important point is the sparing of animal experiments based on our broad knowledge that human (patho)physiology is significantly different from mice (or other species). Many decades of in-vivo research have demonstrated that only a negligible proportion of therapeutic approaches could be translated from rodents to humans. In conclusion, 3D cell culture models can elegantly support our efforts to gain more knowledge for precision cancer medicine as they present powerful tools for generating more clinically relevant information. A broader implementation of the 3D methodology is likely to underscore our efforts to better understand tumor and normal cell radiation responses and foster identification of most critical cancer targets.

Background: Glioblastoma multiforme (GBM) is characterized by genetic and epigenetic alterations in resistance-mediating genes and destructive infiltration of the surrounding brain. Cell adhesion molecules play an important role in therapy resistance. One of these cell adhesion molecules is the Discoidin Domain Receptor 1 (DDR1) facilitating binding to the extracellular matrix protein collagen type-1. Here, we evaluated the so far unknown role of DDR1 in GBM radiochemoresistance including analysis of the underlying molecular mechanisms.
Methods: DDR1 expression (tumor vs. normal) was investigated (Oncomine database). DDR1 targeting (DDR1-IN-1 inhibitor and siRNA) as single treatment and in combination with either irradiation or radiochemotherapy using Temozolomide (TMZ) was conducted to identify its radiochemosensitizing potential in GBM stem-like (GS-5, GS-8) and primary GBM cell populations (DK32, DK41, DK42) (Sphere Formation Assay, 0-6 Gy X-rays) as well as in an orthotopic GBM mouse model. Alterations of signal transduction upon DDR1 inhibition were examined by Western blotting and broad spectrum phosphoproteome analysis. A search for direct DDR1 binding partners was executed by sequential immunoprecipitation/mass spectrometry employing wildtype and truncated DDR1 variants and GST-pulldown.
Results: Database analysis revealed a 3-fold increased DDR1 expression in GBM compared with normal brain (Oncomine). GBM stem-like and patient-derived GBM cell cultures treated with DDR1-IN-1 showed significantly enhanced radiosensitivity in vitro. Intriguingly, a combined DDR1-IN-1/TMZ regimen plus irradiation significantly delayed tumor growth and prolonged survival of mice bearing orthotopic GBM. Mechanistically, a 14-3-3/Beclin-1 protein complex identified by MS/MS connects DDR1 to the pro-survival Akt-mTOR axis. Upon DDR1 inhibition, we observed dissociation of this protein complex followed by abrogated Akt-mTOR signaling, induction of LC3b expression and formation of LC3b-positive autophagosomes. Direct binding of 14-3-3 to DDR1 was confirmed by DDR1 deletion variants and GST-pulldown.
Conclusion: Our data demonstrate that DDR1 is a potential target in GBM and its pharmacological inhibition effectively mediates radiochemosensitization via induction of autophagy that is superior to the conventional therapy.

Fragestellung: Die schlechte Prognose von Glioblastoma multiforme (GBM) Patienten beruht maßgeblich auf Therapieresistenzen von GBM Stamm- und Tumorzellen und deren invasiven Ausbreitung im Gehirn. Hierbei spielen auch durch die Therapie induzierte Anpassungsmechanismen eine besondere Rolle. Um simultan zur Radiochemotherapie diese Anpassungsmechanismen zu hemmen, haben wir Überlebenssignalkaskaden über beta1 Integrine und die Stress-assoziierten c-Jun N-terminalen Kinasen (JNK) in GBM Zellen gehemmt und die Effektivität dieser Kombinationstherapie auf Radiochemosensibilisierung und Zellinvasion in-vitro und in-vivo analysiert.
Methodik: Zum Vergleich der Expression von JNK, beta1 Integrin und Kollagen Typ-I in GBM und Normalgewebe wurde eine Oncomine Datenbank Analyse durchgeführt. Das klonogene Überleben und die Invasion humaner GBM Zelllinien (U343-MG, T4), Stamm-ähnlicher (GS-8) und aus Patienten stammender GBM Zellen (DK32, DK42) wurden nach Bestrahlung (0-6 Gy Röntgen) in 2- und 3-dimensionaler Kollagen Typ-1 Matrix analysiert. Ergänzend dazu wurde eine Einzel- oder Doppelhemmung von beta1 Integrinen (AIIB2) und JNK (SP600125, siRNA) durchgeführt. Weiterhin wurden die Effekte einer Doppelhemmung in Kombination mit Radiochemotherapie auf Tumorwachstum und Überleben im orthotopen GBM Modell getestet. Veränderungen in der zugrundeliegenden zellulären Signaltransduktion (Phosphoproteomanalyse), Zellzyklus (FACS), DNA Schäden (53BP1 Foci) und Chromatinorganisation (Western Blot) wurden unter den genannten Behandlungsbedingungen evaluiert.
Ergebnisse: Oncomine Daten zeigen eine erhöhte Expression von beta1 Integrin und Kollagen Typ-I im GBM. Obwohl eine Einzelhemmung von beta1 Integrinen und JNK das Zellüberleben verringerte, führte nur eine Doppelhemmung beider Moleküle zur Strahlensensibilisierung und Invasionshemmung in allen getesteten GBM Zellpopulationen. Dieser Effekt basierte auf einer Adaptions-bedingten Erhöhung der beta1 Integrin Expression nach JNK Hemmung. Auch im orthotopen GBM Mausmodell führte ein beta1 Integrin/JNK Co-Targeting in Kombination mit Radiochemotherapie zu einer signifikanten Verzögerung des Tumorwachstums und einem längeren mittleren Überleben. Mechanistisch war dabei die Strahlensensibilisierung nach beta1 Integrin/JNK Hemmung auf eine erhöhte ATM Phosphorylierung und dem damit verbundenen G2/M Zellzyklusarrest zurückzuführen, der von einer erhöhten Anzahl an 53BP1 Foci und gesteigertem Euchromatingehalt begleitet wurde.
Schlussfolgerung: Unsere Daten zeigen, dass eine kombinierte beta1 Integrin/JNK Hemmung effizient die Radiochemoresistenz und Invasion von GBM Zellen verringert. Für eine Therapieoptimierung beim Glioblastom als auch bei anderen Malignomen birgt das Verständnis von Therapie-induzierten Adaptionsmechanismen ein großes Potenzial.

Background: The poor prognosis of patients suffering from Glioblastoma multiforme (GBM) is mainly basedon therapy resistances of GBM stem- and tumor bulk cells and their invasive growth within the brain. Neglected are therapy-induced adaptation mechanisms. Here, we blocked bypass mechanisms simultaneously to radiochemotherapy by targeting the pro-survival beta1 integrins and the stress-related c-Jun N-terminal kinases (JNK) and evaluated the effectiveness of this strategy on GBM radiochemosensitization and invasion in vitro and in vivo.
Methods: An Oncomine database analysis was conducted to compare the expression of JNK, beta1 integrin and collagen type-I in GBM and brain. The clonogenic survival and the invasion of human GBM cell lines (U343-MG, T4), GBM stem-like (GS-8) and patient-derived cells (DK32, DK41) was quantified upon irradiation (0-6 Gy X-ray) in 2- and 3-dimensional collagen type-I matrix. On top of this treatment, beta1 integrins (AIIB2) and JNK (SP600125, siRNA) were inhibited in a single or dual manner. The effect of a combined beta1 integrin/JNK inhibition on tumor growth and survival was evaluated in orthotopic GBM mice treated with radiochemotherapy. Furthermore, underlying changes of cellular signaling cascades (phosphoproteome array), cell cycle (FACS), DNA damage (53BP1) and chromatin organization were evaluated upon beta1 integrin/JNK co-targeting.
Results: Oncomine data showed an increased expression of beta1 integrins and collagen type-I in GBM. While neither a single inhibition of beta1 integrins nor JNK reduced cell survival, co-targeting of both molecules induced radiosensitization and blocked cell invasion in all GBM cell populations tested. This treatment effect was promoted by an increased expression of pro-survival beta1 integrin upon JNK inhibition. Moreover, in combination with radiochemotherapy, beta1 integrin/JNK co-inhibition significantly delayed tumor growth in vivo leading to a significant longer survival of orthotopic GBM mice. Mechanistically, the radiosensitization upon beta1 integrin/JNK targeting was attributed to an amplified ATM phosphorylation and G2/M cell cycle arrest, which was accompanied by an increase in 53BP1 foci and euchromatin formation.
Conclusion: Our data show that a combined deactivation of beta1 integrin/JNK efficiently targets adaptation mechanisms and reduces GBM radiochemoresistance and invasion. Further understanding of therapy-induced bypass mechanisms is key for therapy optimization for GBM and other malignancies.

Introduction: Resistance to cancer therapies is a major unsolved challenge. One responsible factor is integrin-mediated adhesion to extracellular matrix. Several studies identified targeting of beta1 integrin receptors as promising approach for radio- and chemosensitization of tumor cells. Although different prosurvival beta1 integrin-mediated signaling pathways were identified, it remains unclear whether they are critically involved in the repair of radiation-induced DNA double strand breaks (DSB). Therefore, we examined the impact of beta1 integrin targeting on DSB repair and describe a regulatory function of beta1 integrins for DNA-PK-dependent but not PARP-dependent non-homologous end-joining (NHEJ).
Materials and methods: To mimic physiological growth conditions in vitro, a 3D cell culture model based on laminin-rich extracellular matrix and tumor xenografts of human head and neck squamous cell carcinoma (HNSCC) cell lines were employed. beta1 integrin targeting was accomplished using the inhibitory monoclonal antibody AIIB2. AIIB2, X-ray irradiation, siRNA-mediated knockdown and inhibitor treatment (FAK, JNK, DNA-PK, PARP) were performed and residual DSB number, NHEJ activity, expression and phosphorylation of various DNA repair proteins as well as clonogenic survival were determined.
Results and discussion: Intriguingly, beta1 integrin targeting impaired the repair of radiogenic DSB (gammaH2AX/p53BP1, pDNA-PKcs T2609 foci) in vitro and in vivo, decreased NHEJ activity and reduced expression and phosphorylation of Ku70, Rad50, Nbs1 and pDNA-PKcs T2609. Further, we identified Ku70, Ku80 and DNA-PKcs but not PARP-1 to reside in the beta1 integrin signaling pathway. It was compelling to observe an additive radiosensitization of 3D grown HNSCC cell lines by dual AIIB2/Olaparib treatment relative to monotherapies. Moreover, FAK and JNK1 were identified as mediators of beta1 integrin-dependent DNA repair.
Conclusion: Here, we support beta1 integrins as promising cancer targets and highlight a regulatory role for beta1 integrins in the DNA-PK-dependent repair of radiation-induced DSB. Further studies are needed to understand the relevance of cell adhesion for nuclear processes and cancer cell therapy resistance.

In this study, the capability of the DYN3D-Serpent codes system to simulate highly heterogeneous sodium-cooled fast systems was investigated. The BFS-73-1 critical assembly was chosen for the investigation. Initially, a 3D full model of the BFS-73-1 critical assembly was simulated using the Serpent Monte-Carlo (MC) code, and the basic neutronic characteristics were evaluated and compared against experimental values. This part meant as a first step towards the use of the Serpent MC code as a tool for preparation of homogenized group constants, and as a reference solution for code-to-code comparison with the DYN3D code. At the second part of the investigation, the BFS-73-1 critical assembly was modeled using the DYN3D code with few-group cross-sections generated by the Serpent MC code. It was suggested that for highly heterogeneous systems, such as the BFS experiments, the Superhomogenization (SPH) method should be applied to correct the few-group cross-sections of the different regions of the system. The SPH method is described and demonstrated for the BFS-73-1 critical assembly. It is shown that the application of the SPH method improves the accuracy of the DYN3D nodal diffusion solution, and therefore, it can be considered as a promising candidate of homogenization method for pin-by-pin calculations of sodium-cooled fast systems.

The Contactless Inductive Flow Tomography is a procedure that enables the reconstruction of the global flow structure of an electrically conducting fluid by measuring the flow induced magnetic field outside the melt and subsequently solving the associated linear inverse problem. The accuracy of the reconstruction depends on the number and the distribution of the sensors around the vessel. The aim of this investigation is to find an optimal sensor configuration for a temperature driven flow of a liquid metal in a cylindrical vessel.

We present the first determination of the N* resonances excitation functions with masses between 1650 MeV/c² and 1900 MeV/c² by means of a combined Partial Wave Analysis of seven exclusively reconstructed data samples for the reaction p+p -> pK⁺Λ measured by the COSY-TOF, DISTO, FOPI and HADES collaborations in fixed target experiments at kinetic energies between 2.14 and 3.5 GeV.

The design of an analog controlled precision heat source is motivated by the measurement of the heat conductivity of liquids. In the framework of an online sensor which is able to measure physical properties like thermal conductivity or thermal diffusion in real time a precise and accurate heat source is required. Constant heat is applied to the material under test to acquire its different properties. Here, the common established methods of constant current or constant voltage may fail, because the heating resistor changes its resistance with temperature. The idea is to utilize a power monitor circuit like the LT2940, which contains an analog multiplier with a control loop around it. The initial design and its assumed uncertainties will be discussed. The first version of the power controller shows an outstanding performance in terms of precision in a steady state. Compared to conventional switching mode power sources the approach with an analog controlled heat source avoids EMI issues as well. The main goal of the present design is a precise heat source with less than 0.5% of error.

Die Open Access Tage 2017 werden in Dresden unter dem Dach von Dresden concept e.V. gemeinsam vom HZDR, der SLUB Dresden und der TU Dresden organisiert. Der Beitrag stellt die Veranstaltung vor.

To improve the public acceptance of the future nuclear power in Europe we have to demonstrate that the new reactors have significantly higher safety level compared to traditional reactors. The ESFR-SMART project (European Sodium Fast Reactor Safety Measures Assessment and Research Tools) aims at enhancing further the safety of Generation-IV SFRs and in particular of the commercial-size European Sodium Fast Reactor (ESFR) in accordance with the European Sustainable Nuclear Industrial Initiative (ESNII) roadmap and in close cooperation with the Advanced Sodium Technological Reactor for Industrial Demonstration (ASTRID) program. The project aims at 5 specific objectives: 1) Produce new experimental data in order to support calibration and validation of the computational tools for each defence-in-depth level. 2) Test and qualify new instrumentations in order to support their utilization in the reactor protection system. 3) Perform further calibration and validation of the computational tools for each defence-in-depth level in order to support safety assessments of Generation-IV SFRs, using the data produced in the project as well as selected legacy data. 4) Select, implement and assess new safety measures for the commercial-size ESFR, using the GIF methodologies, the FP7 CP-ESFR project legacy, the calibrated and validated codes and being in accordance with the update of the European and international safety frameworks taking into account the Fukushima accident. 5) Strengthen and link together new networks, in particular, the network of the European sodium facilities and the network of the European students working on the SFR technology. Close interactions with the main European and international SFR stakeholders—Generation-IV International Forum (GIF), ASTRID Research and Development Cooperation
(ARDECo), ESNII and IAEA—via the Advisory Review Panel will enable reviews and recommendations on the project’s progress as well as dissemination of the new knowledge created by the project. By addressing the industry, policy makers and general public, the project is expected to make a meaningful impact on economics, environment, EU policy and society.

An OECD/NEA sub-group on Uncertainty Analysis in Modelling (UAM) for Design, Operation and Safety Analysis of Sodium-cooled Fast Reactors (SFR-UAM) has been formed under the NSC/WPRS/EGUAM and is currently undertaking preliminary studies after having specified a series of benchmarks.
The incentive for launching the SFR-UAM task force comes from the desire to utilize current understanding of important phenomena to define and quantify the main core characteristics affecting safety and performance of SFRs. Best-estimate codes and data together with an evaluation of the uncertainties are required for that purpose, which challenges existing calculation methods. The group benefits from the results of a previous Sodium-cooled Fast Reactor core Feed-back and Transient response (SFR-FT) Task Force work under the
NSC/WPRS/EGRPANS.
Two SFR cores have been selected for the SFR-UAM benchmark, a 3600MWth oxide core and a 1000MWth metallic core. Their neutronic feedback coefficients are being calculated for transient analyses. The SFR-UAM sub-group is currently defining the grace period or the margin to melting available in the different accident scenarios and this within uncertainty margins. Recently, the work of the sub-group has been updated to incorporate new exercises, namely, a depletion benchmark, a control rod withdrawal benchmark, and the SUPER-PHENIX start-up transient. Experimental evidence in support of the studies is also being developed.

One of the tasks of the OECD/NEA sub-group on Uncertainty Analysis in Modeling (UAM) of Sodium-cooled Fast Reactors (SFR-UAM) under the NSC/WPRS/EGUAM is to perform a code-to-code comparison on neutronic feedback coefficients and associated uncertainties calculated for transient analyses. This benchmark exercise benefits from the results of a previous Sodium-cooled Fast Reactor core Feedback and Transient response (SFR-FT) Task Force work under the NSC/WPRS/EGRPANS. Two SFR cores have been selected for the SFR-UAM benchmark, the 3600MWth oxide and the 1000MWth metallic SFR cores.
Results from six and nine participating international institutes were received for respectively, the metallic and oxide SFR cores, using a wide range of calculation methodologies. The preliminary results display good agreement in the reactivity coefficients estimated, with remaining discrepancies explained by different nuclear data libraries, modeling approximations for deterministic solutions, and statistical convergence for stochastic evaluations on small perturbations. Nuclear data uncertainty evaluations for the reactivity coefficients from two institutions are compared and show consistent results.

An OECD/NEA sub-group on Uncertainty Analysis in Best-Estimate Modelling (UAM) for Design, Operation and Safety Analysis of Sodium-cooled Fast Reactors (SFR-UAM) has been initiated in 2015 with the objective to study the uncertainties in different stages of Sodium Fast Reactors.
Best-estimate codes and data together with an evaluation of the uncertainties are required for that purpose, which challenges existing calculation methods. Neutronic status and reactivity feedback coefficients as well as the kinetic parameters are being calculated for transient analyses. Experimental evidence in support of the studies is also being developed.
The use of the Iterated Fission Probability method in the Monte Carlo codes such as Tripoli4® SERPENT-2 and MCNP-6 gives reference values for calculating βeff as well as Λeff and their uncertainties. Deterministic codes like ERANOS and PARTISN/SUSD3D are also used for nuclear data sensitivity analysis and uncertainty propagation. The computational approaches are tested using available integral experiments and the uncertainties of the measurements. A vast series of experiments has been selected and analysed leading to recommendations on the tools, procedures and data to be used for eff and/or transition functions calculating of the benchmarks including uncertainties.

Microorganisms indigenous to rock salt must be considered for the safety analysis of a final repository for radioactive waste in a salt rock formation. Metabolic activity can cause microbial induced redox processes and influence radionuclide speciation and solubility. Additionally, passive biosorption onto living as well as dead biomass may affect the migration of radionuclides [1].
An extremely halophilic archaeon indigenous to rock salt was used for this study. Two similar strains with different origin were compared concerning their interaction processes with uranium. Halobacterium noricense DSM 15987 was originally isolated from an Austrian salt mine [2], the second strain Halobacterium putatively noricense was isolated from the Waste Isolation Pilot Plant (WIPP) [3].
[1] Lloyd, J. R. et al., Interactions of Microorganisms with Radionuclides (Eds. M. J. Keith-Roach, F. R. Livens), 313-342 (2002).
[2] Gruber, C. et al., Extremophiles, 8, Page 431-439 (2004).
[3] Swanson, J. S. et al., Status Report on the Microbial Characterization of Halite and Groundwater Samples from the WIPP - Status report Los Alamos National Laboratory, Page 1ff. (2012).

AZNHEX is a neutron diffusion code for hexagonal-z geometry currently under development as part of the AZTLAN project in which a Mexican platform for nuclear core simulations is being developed. The diffusion solver is based on the RTN0 (Raviart-Thomas-Nédélec of index 0) nodal finite element method together with the Gordon-Hall transfinite interpolation which is used to convert, in the radial plane, each one of the four trapezoids in a hexagon to squares. The main objective of this work is to test the AZNHEX code capabilities against two well-known diffusion codes DYN3D and PARCS. In a previous work, the Serpent Monte Carlo code was used as a tool for preparation of homogenized group constants for the nodal diffusion analysis of a large U-Pu MOX fueled Sodium-cooled Fast Reactor (SFR) core specified in the OECD/WPRS neutronic SFR benchmark. The group constants generated by Serpent were employed by DYN3D and PARCS nodal diffusion codes in 3D full core calculations. A good agreement between the reference Monte Carlo and nodal diffusion results was reported demonstrating the feasibility of using Serpent as a group constant generator for the deterministic SFR analysis. In order to verify the under development solver inside AZNHEX, the same Serpent generated cross sections sets for each material were exported to AZNHEX format for four different states (as in DYN3D and PARCS): a) a reference case in which the multiplication factor (keff) is the compared value, b) the Doppler constant (KD), c) the sodium void worth, and d) the total control rod worth. Additionally, the radial power distribution was also calculated. The results calculated with AZNHEX showed also a quite good agreement in the direct comparison with DYN3D (-66 pcm in keff) and PARCS (-109 pcm in keff) and therefore against the Serpent reference solution (-194 pcm in keff). As AZNHEX is still under development further improvements will be implemented and new tests will be carried out, but so far the results presented here give confidence in the development.

The nodal diffusion code DYN3D is under extension for Sodium cooled Fast Reactor (SFR) applications. As a part of the extension a new model for axial thermal expansion of fuel rods was developed. The model provides a flexible way of handling the axial fuel rod expansion that is each sub-assembly and node can be treated independently. In the current paper the new model will be described in details. The performance of the model will be assessed with the help of the benchmark on the control rod withdrawal tests performed during the PHÉNIX end-of-life experiments. The DYN3D results will be tested against the experimental data as well as against the numerical results provided by other participants to the benchmark.

The physico-chemical properties of the potassium neptunate K2NpO4 have been investigated in this work using X-ray diffraction, X-ray Absorption Near Edge Structure (XANES) spectroscopy at the Np-L3 edge, and low temperature heat capacity measurements. A Rietveld refinement of the crystal structure is reported for the first time. The Np(VI) valence state has been confirmed by the XANES data, and the absorption edge threshold of the XANES spectrum has been correlated to the Mossbauer isomer shift value reported in the literature. The standard entropy and heat capacity of K2NpO4 have been derived at 298.15 K from the low temperature heat capacity data. The latter suggest the existence of a magnetic ordering transition around 25.9 K, most probably of the ferromagnetic type.

For the final storage of radioactive waste in a deep geological formation rock salt is a potential host rock. Indigenous microorganisms and its interactions with radionuclides have to be considered for the safety performance of the repository in terms of a worst case scenario, where radionuclides are potentially released from the storage site. Therefore, two extreme halophilic microorganisms, which originally occur in rock salt, were used to study its interactions with uranium. The kinetics of uranium bioassociation onto cells of the extreme halophilic archaeon Halobacterium noricense DSM 15987 and the moderate halophilic bacterium Brachybacterium sp. G1 were investigated in detail in batch experiments. For the understanding on a molecular level, in situ infrared spectroscopy was applied, monitoring the bioassociation processes online.
It turned out, that the mechanism of uranium association onto the two different microorganisms differs. The studies were performed at 1.7 M NaCl and 3 M NaCl for the bacterium and archaeon, respectively, to keep the essential osmotic pressure. Both experiments started with washed cells from the exponential growth phase at an initial U(VI) concentration of 40 µM U(VI) at pCH+ 6 (corrected pH due to the presence of high chloride concentration). The occurring process for Brachybacterium sp. G1 was a fast biosorption process, which was completed after 1 h. Infrared spectroscopy showed that only carboxylate functional groups were involved in uranium sorption. In contrast, the association onto H. noricense was a rather complex, multistage process [1]. Within the first hour, an association was observed, which was followed by a desorption phase for about 4 hours. Subsequently, uranium was bioassociated again over the timeframe of one week. Apart from carboxylate functional groups, contributions of phosphoryl groups to uranium binding were evidenced by infrared spectroscopy. The occurrence of the multistage uranium association was furthermore visualized with scanning electron microscopy.
[1] Bader, M et al. (2017) J. Hazard. Mater. 32, 225 – 232.

3D reactor dynamic code DYN3D was developed for analysis of transients and accident scenarios. The residual radioactive decay heat plays an important role in some of accident scenarios and in DYN3D it is taken into account by a model based on German national standard DIN Norm 25463. The applicability of this model is limited to a low enriched uranium dioxide fuel for light water reactors.
This paper describes the new general decay heat model implemented in DYN3D. The radioactive decay rate of each nuclide in each spatial node is calculated and the cumulative released heat is used to obtain the decay power spatial distribution for any time step. Such explicit approach is based on first principles and is free from approximations which limit its applicability. The proposed method is verified against Monte Carlo reference calculations.

A review of published work on the physics and modelling of flashing flows is presented. The term “flashing” refers to a familiar phase change phenomenon initiated by pressure drop. It has gained a great deal of attention due to various industrial safety concerns. Nevertheless, knowledge about the involved physical processes such as formation and growth of bubbles in superheated liquid, and information for appropriate modelling in practical systems is still far from sufficiency. The present work is aimed to provide a brief but comprehensive overview of available theoretical models for these sub-phenomena as well as general modelling frameworks. This kind of review is necessary and helpful for further understanding and investigation of flashing flows in more detail.

Three-dimensional ex vivo cell cultures mimic physiological in vivo growth conditions thereby significantly contributing to our understanding of tumor cell growth and survival, therapy resistance and identification of novel potent cancer targets. In the present study, we describe advanced three-dimensional cell culture methodology for investigating cellular survival and proliferation in human carcinoma cells after cancer therapy including molecular therapeutics. Single cells are embedded into laminin-rich extracellular matrix and can be treated with cytotoxic drugs, ionizing or UV radiation or any other substance of interest when consolidated and approximating in vivo morphology. Subsequently, cells are allowed to grow for automated determination of clonogenic survival (colony number) or proliferation (colony size). The entire protocol of 3D cell plating takes ~1 h working time and pursues for ~7 days before evaluation. This newly developed method broadens the spectrum of exploration of malignant tumors and other diseases and enables the obtainment of more reliable data on cancer treatment efficacy.

Beside the nuclear reactor and its primary circuit the spent fuel pool is yet another safety-critical part in a nuclear power plant which has gained increasing focus after the Fukushima accident. Loss of coolant or enduring loss of cooling conditions would ultimately result in loss of cladding integrity at elevated temperatures with excessive release of fission products and hydrogen. To predict the available response time and to assess the efficacy of mitigating measures computer simulations can be employed. Their validity, however, needs to be proven by dedicated experiments at lower scale but relevant thermal hydraulic conditions. For that purpose, the test facility ALADIN was designed, which enables conduction of experiments on a single BWR fuel element mock-up under loss of coolant and loss of cooling accident conditions. In this paper we introduce the facility and its instrumentation, with a focus on temperature sensors and a new thermal anemometry grid sensor for spatially resolved flow velocity measurement of the superheated steam in the subchannels together with the affiliated calibration procedure.

Modeling mineral microstructures is of high importance in geostatistics in order to render realistic geological patterns. An appropriate model should be applicable to varying microstructures and account for correlations within the facies, i.e., the shape and size of the grains as well as for dependencies between the facies, e.g., facies A lies within facies B, or facies A and B are not connected. This allows to simulate the geometry of a microstructure in combination with other microstructural properties like mineralogy, crystall lattice orientation, (locally varying) chemical composition, inclusions, grain boundaries, subgrain boundaries and defects.

The common plurigaussian method, a valuable approach in geostatistics, can account for correlations within each facies and in principle be extended to correlations between the facies. Founded on particular case of this model, formulas for first- and second-order characteristics, such as volume fraction, correlation function and cross-correlation function can be given by a multivariate normal distribution, which makes model fitting more feasible. Based on first- and second-order statistics which can easily
be estimated by convolution, model fitting requires only numerical inversion of several one-dimensional monotone functions in this model.

The applicability is demonstrated for the two-dimensional case by modeling the microstructure
from a Mineral Liberation Analyzer image data set and evaluated by a deviation test.

The new intermetallic uranium beryllium germanide UBeGe and its thorium analogon ThBeGe crystallize with the hexagonal ZrBeSi type of structure. Studies of magnetic, thermal, and transport properties were performed on polycrystalline samples between 1.8 and 750K. UBeGe is a uniaxial ferromagnet and there are indications for two magnetic transitions at Tc(1) ≈ 160K and Tc(2) ≈ 150K. The high paramagnetic effective moment μeff ≈ 3 1μB, x-ray absorption near-edge spectroscopy (XANES, 17–300 K), as well as theoretical DFT calculations indicate localized U 5f2 states in UBeGe. ThBeGe is a diamagnetic metallic material with low density of states at the Fermi level.

We report on generic experimental studies dealing with the direct contact condensation of steam at a falling sub-cooled water jet at high pressure and temperature. This generic problem concerns some safety-relevant thermal hydraulic scenarios in light water reactors. One of such is the question for heat transfer and mixing when a sub-cooled jet of water in an emergency core-cooling scenario enters a hot pressurized component of the primary reactor circuit. The involved phenomena of heat transfer are complex in this case, reaching from direct condensation of steam via steam bubble entrainment to single phase mixing of hot and cold water.
Experiments were performed in the TOPFLOW pressure tank, which is an experimental facility for high-pressure thermal hydraulics experiments in pressure equilibrium. The facility has been designed for studying steam-water two-phase flows at pressures of up to 50 bar. It enables to run experiments in flow domains of complex shape without high difference pressures across the wall. The concept therefore allows us to use thin metal walls and even glass windows to observe flows in complex geometry domains with the help of IR or video camera and to considerably reduce cost and complexity of experimental installations.

Since their discovery, fullerenes have become one of the most recognizable molecules in science. The “beautiful molecule” described by Sir Harold Kroto has been subtly referenced in movie, and has adorned the covers of many science-based textbooks. The physical and chemical properties of fullerenes have generated a lot of interest in the science community with many opportunities to develop new avenues for scientific research. However, the difficulties in the commercial use of fullerenes, such as C60, have likely been due to issues with solubility. Fortunately, the situation has improved over the last decade with research into fullerene derivatives. Once modified, fullerenes may have applications in a variety of areas, including medicine, drug delivery, optoelectronics, and electrochemistry. The addition of low concentrations of carbon nanoparticles to polymer matrices may result in significant changes in the function of polymer-based composite materials.
This review will highlight the applications of fullerene derivatives as nano-additives for polymer composites. In this review, fullerene derivatives, such as water-soluble carbon nanoclusters (hydroxyl and carboxyl groups), and hydrophobic fullerenes, such as metallofullerenes and methanofullerenes, will be evaluated in regards to their potential impact on commercial applications, such as photovoltaic devices, fuel cells, membrane technology and biocompatible electroactive actuators.

Beitrag zum Tagungsband zur Veranstaltung "Economic Governance und Ordonomik 2016", welche in Halle im Festsaals des Siedehauses des Technischen Halloren- und Salinemuseums stattgefunden hat und auf der die Ergbnisse zum Projekt SMSB (Re-Mining) in einem Vortrag präsentiert wurden.

Ein wichtiges Ziel des SMSB Projektes war es Technologien für eine möglichst effiziente und wirtschaftliche Aufbereitung strategischer Metalle und Mineralien aus Bergbauhalden mit besonders hohem Rohstoffpotential zu entwickeln. Dafür wurden verschiedene Ansätze gewählt. Es Zunächst wurde das beinhaltete Rohstoffpotential ausgewählter Haldenkörper durch Bohrungen und umfassende mineralogische und chemische Analytik konkretisiert. Dann wurden Versuche zur chemischen und biologischen Laugung an Haldenmaterial durchgeführt, aber auch moderne mechanische Aufbereitungsverfahren auf ihre Anwendbarkeit getestet. Mithilfe der nachgeschalteten Metallurgie wurden die gewonnenen Konzentrate weiter untersucht und Metalle aus diesen extrahiert. Auf die Versuche und Ergebnisse zur Aufbereitung sowie der Metallurgie wird in diesem Beitrag nicht näher eingegangen. Die Ergebnisse sind im SMSB Abschlussbericht zu finden. Aus den Resultaten von SMSB wurde ein Kataster der zwanzig bedeutendsten sächsischen Bergbauhalden erstellt. Diese Informationen wurden gemeinsam mit den Ergebnissen von zwei weiteren r³-Projekten, den Projekten ROBEHA mit Fokus Harz und ReStrateGIS mit Fokus Saarland, Ruhrgebiet und Thüringen zusammengeführt. Dabei wurde ein gemeinsames Haldenkataster erzeugt. Weiterhin wurden die Methoden zur Charakterisierung, Erkundung und Aufbereitung der Halden zusammengetragen und in einem gemeinsamen Methodenhandbuch zusammengestellt. Einige dieser Ergebnisse werden in diesem Beitrag vorgestellt.

Projektbericht über das Projekt SMSB - Gewinnung strategischer Metalle und Mineralien aus sächsischen Bergbauhalden. Das Projekt SMSB hatte zum Ziel, die zwanzig größten Metallerzbergbauhalden Sachsens zu erfassen und in einem Kataster zusammenzufügen. Die Davidschachthalde in Freiberg und die Tiefenbachhalde in Altenberg wurden als zwei Flotations-Rückstandshalden mit besonders hohem Wertstoffpotenzial identifiziert durch jeweils 10 Bohrungen im Detail erkundet. Aus den Bohrkernen wurden insgesamt 207 Proben entnommen und ihr Stoffbestand mit verschiedenen chemischen und mineralogischen Analyseverfahren quantifiziert. Weiterhin wurden an dem gewonnen Probenmaterial verschiedene Aufbereitungsverfahren im Labormaßstab getestet. Diese Versuche hatten das Ziel, geeignete Technologien für das Abtrennen von Wertstoffen aus dem Haldenmaterial zu identifizieren. Resultate belegen, dass sich die Tiefenbachhalde insbesondere durch hohe Gehalte an Zinn, die Davidschachthalde dagegen durch hohe Konzentrationen von Indium, Blei und Zink auszeichnen. Das Zinn in der Tiefenbachhalde ist durch ein einziges Oxidmineral (Kassiterit) vertreten, während die Wertstoffe in der Davidschachthalde an eine komplexe Vergesellschaftung von Sulfiden gebunden sind. Arsen – in der Form von Arsenopyrit – ist das einzige wesentliche Schadelement in dem Material der Tiefenbachhalde. In den Rückständen der Davidschachthalde dagegen sind die Schadstoffe Arsen und Cadmium sehr eng mit den Wertstoffen assoziiert, oft vertreten in den gleichen Erzmineralien. Aufbereitungstests belegen, dass Wert- und Schadstoffe aus der Spülhalde Davidschacht sehr effizient durch biologische Laugung mobilisiert und entfernt werden können, für die Tiefenbachhalde wurde dagegen die Flotation als geeignete Aufbereitungstechnologie identifiziert.Anhand der gewonnenen Daten und erzielten Versuchsergebnisse wurden für die beiden Halden dreidimensionale Ressourcenpotenzial-Modelle erstellt, die auf Kombinationen von gewichteten aufbereitungsrelevanten Parametern fußen. Die einzelnen Parameter haben einen Einfluss darauf, wie effizient eine gewählte Aufbereitungstechnologie auf das vorhandene Haldenmaterial wirken kann.

Ambidexterity, defined as the capability to develop both incremental and radical innovations, is an important driver of firm success. Idea generation is an essential starting point for both types of innovation. Therefore, this study investigates whether ambidextrous idea generation, defined as the capability to actively generate both incremental and radical ideas, affects new product development (NPD) success. Analyses on the Comparative Performance Assessment Study (CPAS) data, which includes data from 453 companies distributed over 24 countries, demonstrate that ambidextrous idea generation does indeed affect NPD program success. Consequently, this study also investigates which antecedents foster ambidextrous idea generation. The innovation paradox concept predicts that achieving ambidexterity requires overcoming paradoxical antecedents. Therefore, we tested whether combinations of financial and breakthrough orientations (the paradox of strategic emphasis), a formal innovation process and an innovation culture (the paradox of innovation drivers), tight and loose customer coupling (the paradox of customer orientation), and internal development and external collaboration (the paradox of openness) affects ambidextrous idea generation. The results show that only customer orientation and openness have the expected inverted u-shaped effect. These finding are in line with construal level theory, which predicts that the organizational characteristics that influence idea-generation activity must be at the same construal level to have the desired effect. The contribution of this study is twofold. First, the analyses indicate that ambidextrous idea generation has significant repercussions for the entire NPD program. Second, the results show that resolving innovation paradoxes only has an effect if the construal level of the paradox and the activity match. This finding indicates an important boundary condition for the innovation paradox concept.

A series of the British nuclear weapons tests conducted between 1953 and 1963 at the southeast area of the Great Victoria Desert, South Australia (Fig. 1(a)), dispersed long-lived and radioactive nuclear debris including plutonium (Pu). A reliable assessment of the environmental impact of these radioactive contaminants and their potential implications for human health requires an understanding of their physical/chemical characteristics at the molecular scale. This study focuses on the physical/chemical characterisation of the Pu contaminant, the most problematic radioactive contaminant remaining at the former testing sites, by synchrotron-based X-ray microscopy / spectroscopy.
The Pu legacy samples investigated in this study were collected at one of the former testing sites, the Taranaki site at Maralinga (Fig. 1(b)). The collected soil samples were physically sieved several times and further fractionated by heavy liquid density separation to isolate a small particle with significantly high radioactivity. The isolated particles were then transported to the X-ray fluorescence microscopy (XFM) beamline at the Australian Synchrotron. The X-ray fluorescence mapping indicates that the particle forms an inhomogeneous core-shell structure composed of a concentrated Pu core coated by the external layer containing Ca, Fe and U.1 This suggests that most of the Pu within the particle is currently unavailable for interaction with the environment, but the bioavailability of Pu could be potentially increased in the future when the particle morphology is further changed by the surface weathers. These findings also highlight the importance of the comprehensive characterization of radioactive contaminants for reliable environmental- and radiotoxicological assessment.

Background
Despite clear differences in clinical presentation and outcome, squamous cell carcinomas of the head and neck (SCCHN) arising from human papilloma virus (HPV) infection or heavy tobacco/alcohol consumption are treated equally. Next-generation sequencing is expected to reveal novel targets for more individualised treatment.

Patients and methods
Tumour specimens from 208 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity, all uniformly treated with adjuvant cisplatin-based chemoradiation, were included. A customised panel covering 211 exons from 45 genes frequently altered in SCCHN was used for detection of non-synonymous point and frameshift mutations. Mutations were correlated with HPV status and treatment outcome.

Results
Mutational profiles and HPV status were successfully established for 179 cases. HPV– tumours showed an increased frequency of alterations in tumour suppressor genes compared to HPV+ cases (TP53 67% versus 4%, CDKN2A 18% versus 0%). Conversely, HPV+ carcinomas were enriched for activating mutations in driver genes compared to HPV– cases (PIK3CA 30% versus 12%, KRAS 6% versus 1%, and NRAS 4% versus 0%). Hotspot TP53 missense mutations in HPV– carcinomas correlated with an increased risk of locoregional recurrence (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.5–12.1, P = 0.006) and death (HR 2.2, 95% CI 1.1–4.4, P = 0.021). In HPV+ SCCHN, driver gene mutations were associated per trend with a higher risk of death (HR 3.9, 95% CI 0.7–21.1, P = 0.11).

Conclusions
Distinct mutation profiles in HPV– and HPV+ SCCHN identify subgroups with poor outcome after adjuvant chemoradiation. Mutant p53 and the phosphoinositide 3-kinase pathway were identified as potential druggable targets for subgroup-specific treatment optimisation.

Compton camera prototype for a position-sensitive detection of prompt γ rays from proton-induced nuclear reactions is being developed in Garching. The detector system allows to track the Comptonscattered electrons. The camera consists of a monolithic LaBr3:Ce scintillation absorber crystal, read out by a multi-anode PMT, preceded by a stacked array of 6 double-sided silicon strip detectors acting as scatterers. The LaBr3:Ce crystal has been characterized with radioactive sources. Online commissioning measurements were performed with a pulsed deuteron beam at the Garching Tandem accelerator and with a clinical proton beam at the OncoRay facility in Dresden. The determination of the interaction point of the photons in the monolithic crystal was investigated.

Cyclin-dependent kinase 9 (CDK9), mainly involved in regulation of transcription, has recently been shown to impact on cell cycling and DNA repair. Despite the fact that CDK9 has been proposed as potential cancer target, it remains largely elusive whether CDK9 targeting alters tumor cell radiosensitivity. Five human head and neck squamous cell carcinoma (HNSCC) cell lines (SAS, FaDu, HSC4, Cal33, UTSCC5) as well as SAS cells stably transfected with CDK9-EGFP-N1 plasmid or empty vector controls were used. Upon either CDK9 small interfering RNA knockdown or treatment with a pan-CDK inhibitor (ZK304709), colony formation, DNA double strand breaks (DSBs), apoptosis, cell cycling, and expression and phosphorylation of major cell cycle and DNA damage repair proteins were examined. While CDK9 overexpression mediated radioprotection, CDK9 depletion clearly enhanced the radiosensitivity of HNSCC cells without an induction of apoptosis. While the cell cycle and cell cycle proteins were significantly modulated by CDK9 depletion, no further alterations in these parameters were observed after combined CDK9 knockdown with irradiation. ZK304709 showed concentration-dependent cytotoxicity but failed to radiosensitize HNSCC cells. Our findings suggest a potential role of CDK9 in the radiation response of HNSCC cells. Additional studies are warranted to clarify the usefulness to target CDK9 in the clinic.

Objective

To validate the impact of HPV status, cancer stem cell (CSC) marker expression and tumour hypoxia status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received postoperative radiotherapy. The results of the exploration cohort have previously been reported by the German Cancer Consortium Radiation Oncology Group (DKTK-ROG; Lohaus et al., 2014; Linge et al., 2016).

Materials and methods

For 152 patients with locally advanced HNSCC the impact of HPV16 DNA status, CSC marker expression and hypoxia-associated gene signatures on outcome of postoperative radiotherapy were retrospectively analysed. Out of them, 40 patients received postoperative radiochemotherapy. Cox models presented in a previous study were validated using the concordance index as a performance measure. The primary endpoint of this study was loco-regional control. Results were compared to those previously reported by DKTK-ROG.

Results

Loco-regional control, freedom from distant metastases and overall survival were inferior to the previously reported cohort. Despite of this, the prognostic value of the combination of HPV infection status, CSC marker expression (SLC3A2) and tumour hypoxia status could be validated in univariate analyses using an independent validation cohort. For multivariate models, the concordance index was between 0.58 and 0.69 in validation, indicating a good prognostic performance of the models. The inclusion of CD44 and the 15-gene hypoxia signature moderately improved the performance compared to a baseline model without CSC markers or hypoxia classifiers.

Conclusions

The HPV status, CSC marker expression of CD44 and SLC3A2 as well as hypoxia status are potential prognostic biomarkers for patients with locally advanced HNSCC treated by postoperative radiotherapy.

β1 Integrin-mediated cell–extracellular matrix interactions allow cancer cell survival and confer therapy resistance. It was shown that inhibition of β1 integrins sensitizes cells to radiotherapy. Here, we examined the impact of β1 integrin targeting on the repair of radiation-induced DNA double-strand breaks (DSBs). β1 Integrin inhibition was accomplished using the monoclonal antibody AIIB2 and experiments were performed in three-dimensional cell cultures and tumor xenografts of human head and neck squamous cell carcinoma (HNSCC) cell lines. AIIB2, X-ray irradiation, small interfering RNA-mediated knockdown and Olaparib treatment were performed and residual DSB number, protein and gene expression, non-homologous end joining (NHEJ) activity as well as clonogenic survival were determined. β1 Integrin targeting impaired repair of radiogenic DSB (γH2AX/53BP1, pDNA-PKcs T2609 foci) in vitro and in vivo and reduced the protein expression of Ku70, Rad50 and Nbs1. Further, we identified Ku70, Ku80 and DNA-PKcs but not poly(ADP-ribose) polymerase (PARP)-1 to reside in the β1 integrin pathway. Intriguingly, combined inhibition of β1 integrin and PARP using Olaparib was significantly more effective than either treatment alone in non-irradiated and irradiated HNSCC cells. Here, we support β1 integrins as potential cancer targets and highlight a regulatory role for β1 integrins in the repair of radiogenic DNA damage via classical NHEJ. Further, the data suggest combined targeting of β1 integrin and PARP as promising approach for radiosensitization of HNSCC.

Published potential mapping procedures usually presume that the covariables are known.
However, covariables are usually interpolated by kriging. In sparsely covered regions reported covariables can seriously differ from the actual situation on the ground. When regressing to the mean we often nd the variation of covariables underestimated, leading to an overestimation of dependence. Similar effects can be observed when the fitted model is applied to prediction: The potential seems promising, but is underestimated in sparsely observed regions.
In earlier publications it has been shown that a Cox regression model is more general than weights of evidence methods, and also independent of a grid with a user defined resolution.
Therefore our investigation is based on this model class. Here we compare four different estimation procedures for Cox regression models: (i) the pseudolikelihood method put forward by Baddeley, (ii) a numerical solution of the full Maximum Likelihood approach based on kriged covariables, (iii) an approximation of the full Maximum Likelihood approach based on the conditional distribution of the covariables, and (iv) the MCMC based Bayesian solution.
The first two methods neglect the uncertainty of the covariables, the latter two account for it. For simulated examples with known true parameters we can show a substantial decrease of estimation errors when the uncertainty is considered.
It can be shown that the estimation error reported by the methods neglecting the uncertainty of covariables seriously underestimates the actual uncertainty of the parameter estimate.

We would like to put the workflows of two point geostats and multi point geostatistics in a common framework of model estimation, model selection, algorithmic parameter selection and than finally simulation and prediction. This workflow is well established in to point geostats. In this contribution we extend it to multi point geostatistics. In this way we can improve the performance by better choices for the all method parameters.
Two point geostatistics typically puts three decisions ahead of each estimation or simulation: Based on the observations we choose a variogram model, estimate its parameters, and select a kriging neighbourhood to weigh between computational speed and algorithmic accuracy.
For Multiple Point statistics simulation methods we typically provide all knowledge about the spatial dependence by a fixed training image. Three different ways for generating training images have been proposed: Real maps or 3D models of the phenomenon, constructed images capturing our knowledge, and realisations of random field models. The random field model used for the simulation could be understood as our model of the distribution of the random field we would like to interpolate. The simulation of the training image and the following multiple point simulation is an imperfect numerical algorithm computing the conditional distribution based on that model. Just like two point geostatistics it again has the patterns as algorithmic parameters describing a geostatistical neighbourhood.
Like with variogram models, for any more complicated random fields models, we have model parameters. Depending on them different sets of observations will have different likelihoods. I.e. like with classical variogram estimation we can estimate the model parameters from the observations. As the likelihoods are typically not computable and variogram based methods can only capture two point dependences, we propose a quasilikelihood based multi point approach for the estimation of these parameters. Analog to variogram model comparison we also propose cross validation based methods to check the fit of the model and the performance of the simulation algorithm on the model. In analogy to the selection of search neighbourhood the simulation performance of the algorithm can be checked against the model.

Block kriging of compositional data is a challenge even in the case of classical linear statistics. Compositional kriging is not unbiased with respect to the quantity used additively in block integration. Classical block kriging can leave the compositional simplex. Compositional data cannot directly be integrated in a block, when the material density varies within the block. For full compositions the density might be a function of the composition. For subcomposition it is typically still correlated. In a previous publication we developed a geostatistical block prediction of compositional data relying on the additive lognormal property of the compositional random field. This assumption is however not always met. Especially in case of multiple facies, we see bimodal distributions leading to substantially different distribution of block values. Due to the non lognormality of the residuals typical lognormal kriging type bias corrections are not appropriate.
For this situation we propose to apply conditional distribution based type of multiple point geostatistics. Based on a training image or a training model, we generate joint dataset of the observations of the block integral value incorporating all relevant corrections (like density correction). The conditional distribution is described by a very general version of a generalized linear model for the conditional distribution. The parameters of this regression model are estimated from the training dataset. Compositional, Euclidean expected values can be computed from the resulting prediction.
The method has the following properties: The Expected difference of true value and prediction is 0. The method provides the full conditional distribution. Not only the mean, but more selected nonlinear functionals can be predict on average correct from the conditional distribution. Due to its underlying Baysian nature the method can in principle outperform averages over conditional simulations with mps or ordinary kriging.

Investigations of the electronic structure of different systems have been the subject of continuous research efforts over the last 100 years. Parallel to the technical developments and experimental discoveries, the theoretical models, describing the observed phenomena, have advanced. The challenges arise in the studies of exotic systems, where the most extraordinary behaviors need to be understood in detail. To improve our understanding, we search for the most extreme experimental methods, testing strange combinations of theoretical approximations; there are still many questions that remain unknown. This is the case of f-electron systems.

The aim of this HDR thesis is to demonstrate the applicability of X-ray spectroscopy for determining the electronic structure of f-electron systems, and to show the importance of theoretical simulations in understanding the experimental results. Special attention has been paid to the high-energy resolution fluorescence detection (HERFD) X-ray absorption near edge structure (XANES), X-ray emission spectroscopy (XES) and resonant inelastic X-ray scattering (RIXS) methods. It is shown here that a combination of high-quality experimental data and theoretical calculations can provide unprecedented detailed information about the electronic structure of actinide and lanthanide systems

We present resonant x-ray emission spectroscopic (RXES) data from the uranium intermetallics UPd3, USb, USn3 and URu2Si2 at the U M4,5 edges and compare the data to those from the well-localized 5f2 semiconductor UO2. The technique is especially sensitive to any oxidation of the surface, and this was found on the USb sample, thus preventing a good comparison with a material known to be 5f3. We have found a small energy shift between UO2 and UPd3, both known to have localized 5f2 configurations, which we ascribe to the effect of conduction electrons in UPd3. The spectra from UPd3 and URu2Si2 are similar, strongly suggesting a predominant 5f2 configuration for URu2Si2. The valence-band resonant inelastic x-ray scattering (RIXS) provides information on the U P3 transitions (at about 18 eV) between the U 5f and U 6p states, as well as transitions of between 3 and 7 eV from the valence band into the unoccupied 5f states. These transitions are primarily involving mixed ligand states (O 2p or Pd, Ru 4d) and U 5f states. Calculations are able to reproduce both these low-energy transitions reasonably well.

Nanotechnology can offer different solutions for enhancing the therapeutic efficiency of polyphenols, a class of natural products widely explored for a potential applicability for the treatment of different diseases including cancer. While possessing interesting anticancer properties, polyphenols suffer from low stability and unfavorable pharmacokinetics, and thus suitable carriers are required when planning a therapeutic protocol. In the present review, an overview of the different strategies based on polymeric materials is presented, with the aim to highlight the strengths and the weaknesses of each approach and offer a platform of ideas for researchers working in the field.

Cancer is one of the leading non-communicable diseases with highest mortality rates worldwide. About half of all cancer patients receive radiation treatment in the course of their disease. However, treatment outcome and curative potential of radiotherapy is often impeded by genetically and/or environmentally driven mechanisms of tumor radioresistance and normal tissue radiotoxicity. While nanomedicine-based tools for imaging, dosimetry and treatment are potential keys to the improvement of therapeutic efficacy and reducing side effects, radiotherapy is an established technique to eradicate the tumor cells. In order to progress the introduction of nanoparticles in radiooncology, due to the highly interdisciplinary nature, expertise in chemistry, radiobiology and translational research is needed. In this report recent insights and promising policies to design nanotechnology-based therapeutics for tumor radiosensitization will be discussed. An attempt is made to cover the entire field from preclinical development to clinical studies. Hence, this report illustrates (1) the radio- and tumor-biological rationales for combining nanostructures with radiotherapy, (2) tumor-site targeting strategies and mechanisms of cellular uptake, (3) biological response hypotheses for new nanomaterials of interest, and (4) challenges to translate the research findings into clinical trials.

Introduction: A malignant tumor is composed of a hierarchically organized, heterogeneous pool of cells in various stages of differentiation including cancer stem cells (CSCs) as the main cell population responsible for tumor initiation, growth and relapse as well as for metastasis formation and therapy resistance. Preliminary work of our group showed that photon irradiation of prostate cancer cells induces an augmentation of the CSC population that can be attributed to an epigenetic reprogramming of non-CSCs into CSCs. The combination of the histone methyltransferase EZH2 inhibitor 3-Deazaneplanocin A (DZNep) with x-ray irradiation leads to a radiosensitization and prevention of the cellular reprogramming of prostate cancer cells in vitro, in vivo and in ex vivo treated primary prostate cancer samples.

Objectives: The aim of this study is (1) the investigation of potential radiosensitizing effects of epigenetic inhibitors for different tumor entities including prostate cancer, head and neck squamous cell carcinoma (HNSCC) and glioblastoma multiforme (GBM); (2) a high throughput screening (HTS) using a chemical library with epigenetic targeting substances to identify novel epigenetic targeting agents for tumor radiosensitization and (3) the correlation of radiation-induced CSC and epigenetic markers after photon versus 150MeV proton irradiation to identify biomarkers for a personalized proton therapy.

Methods: Evaluation of the cytotoxicity (MTT-Assay, CellTiterGlo®-Assay), radiosensitivity (colony formation assay), DNA repair capacity (γH2AX foci assay), CSC marker expression (Flow cytometry) and histone modifications (Western blot) for prostate cancer (DU145, PC3), HNSCC (FaDu, Cal33) and GBM (LN229, U87MG) cell lines using different clinically relevant epigenetic modulators in combination with irradiation.

Results: Our results show that epigenetic marks including histone modifications are modulated after ionizing radiation in the different tumor entities including prostate cancer, HNSCC and GBM and that treatment with some epigenetic inhibitors leads to the radiosensitization of cancer cells. Furthermore, we found differences in CSC marker expression and epigenetic modulation after photon versus proton irradiation.

Conclusion: Epigenetic targeting therapy may be useful as a co-therapy strategy to prevent tumor cell reprogramming and promote radiosensitization of the different tumor entities. Moreover, CSC and histone mark-based biomarkers can be potentially used as predictive markers for a personalized radiotherapy.

Retrospective analyses of CSC-related biomarkers followed by prospective validation studies in patients with locally advanced HNSCC are currently being performed in an ongoing multicentre retrospective – prospective trial conducted by the Radiation Oncology Group of the German Cancer Consortium (DKTK-ROG) For the patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with a curatively intended cisplatin-based postoperative radiochemotherapy or primary radiochemotherapy, the expression level of SLC3A2 (Solute Carrier Family 3 member 2), a putative cancer stem cell marker was positively correlated with poor locoregional control in locally advanced (HNSCC) [1, 2].
The human gene SLC3A2 encodes the heavy chain of CD98; a ~125 kDa heterodimeric L-type amino acid transporter. CD98hc also interacts with integrin β subunit and has a putative role in regulating integrin signaling, which controls cell proliferation, survival, migration, and epithelial adhesion [3].
The aim of this study is to elucidate the potential role of stem cell marker CD98hc in regulation of the HNSCC radiosensitivity.
The expression levels of CD98 in nine HNSCC cell lines measured by western blot analysis and flow cytometry were positively correlated with their respective in vivo tumor control dose 50 (TCD50) values (ref). An increase of CD98hc expression was also detected by Western blotting in the radioresistant derivatives of the established HNSCC cells as compared to their parental counterparts. In addition, expression of CD98hs was induced in the parental HNSCC cells after single dose irradiation of HNSCC cells with 4Gy of X-ray.
To analyze a functional role of CD98hc in the regulation of HNSCC radioresistance, SLC3A2 (gene of CD98hc) was knocked down via siRNA in Cal33, Fadu, UT5 and SAS cells, which then were subjected to the radiobiological colony formation assays. A knockdown of SLC3A2 in HNSCC cells followed by irradiation decreased the capability for colony formation compared to the cells transfected with scrambled siRNA.
For further in vitro and in vivo experiments, cell lines with a low CD98hc level were established using CRISPR/Cas9 technology. Off-targets were reduced using a modified CRISPR/Cas9-variant that was confirmed by PCR and sequencing experiments.
In addition, a recombinant neutralizing antibody against CD98hc is currently tested as possible CD98hc targeted and radiosensitizing therapy.
Finally, publicly available TCGA-gene dataset for HNSCC patients treated with and without radiotherapy was used to analyze a potential correlation of SLC3A2 expression with expression of other genes and clinical outcome of the HNSCC patients.
The results support the hypothesis that CD98hc is playing a role in the regulation of HNSCC radioresistance. In the future CD98hc may be used as a prognostic marker and become a potential target for combined radiochemotherapy in locally advanced HNSCC.

References:

[1] Linge, A., Lock, S., Gudziol, V., Nowak, A., Lohaus, F., von Neubeck, C., Jutz, M., Abdollahi, A.,
Debus, J., Tinhofer, I., et al. (2016). Low CSC marker expression and low hypoxia identify good
prognosis subgroups in HPV(-)HNSCC after postoperative radiochemotherapy: a multicenter study
of the DKTK-ROG. Clin. Cancer Res.
[2]. https://www.ncbi.nlm.nih.gov/pubmed/27913065
[3]Cantor, J.M., Ginsberg, M.H., 2012. CD98 at the crossroads of adaptive immunity and cancer. J Cell Sci 125, 1373–1382. doi:10.1242/jcs.096040

Background: CD98hc protein is encoded by the SLC3A2 (solute carrier family 3 member 2) gene. CD98hc contributes to the amino acid transport and regulation of the integrin signaling pathway, and is a putative marker of cancer stem cells (CSCs). Recent retrospective analyses showed a correlation of high SLC3A2 expression with poor locoregional control in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with a curatively intended cisplatin-based postoperative radiochemotherapy or primary radiochemotherapy. The aim of this study is the investigation of potential molecular mechanisms of action of CD98hc as a regulator of HNSCC radioresistance. Methods: The expression levels of CD98 in nine HNSCC cell lines were measured by Western blot analysis and correlated with corresponding tumor control dose 50 (TCD50) values. The fractions of plasma membrane proteins from Cal33 and FaDu cells and their radioresistant sublines established by fractionated irradiation with a total dose of ≥50Gy of X-rays were enriched by differential centrifugation and quantitatively analyzed by tandem mass spectrometry. To determine the role of SLC3A2 in the regulation of cell radioresistance, HNSCC cell lines and their respective irradiated sublines were transfected with SLC3A2 siRNAs and analysed by 2D and/or 3D radiobiological clonogenic assays after X-ray irradiation. The CRISPR/Cas9 system was used for the stable monoallelic knock-out of SLC3A2 in HNSCC cells. The efficiency of DNA repair after irradiation was examined by γH2A.X foci analysis. The Cancer Genome Atlas (TCGA) gene dataset for HNSCC patients treated with and without radiotherapy was used to analyse a potential correlation of SLC3A2 expression with expression of other genes and with clinical outcome of the HNSCC patients. Results and Discussion: The data of proteomic profiling, the results of Western blot analysis correlated to TCD50 values, the functional assessment of the SLC3A2 knockdown and knockout cells along with analysis of the TCGA datasets confirmed a connection between the CD98hc expression level and the cancer cell radiosensitivity in vitro and in vivo. These results support the hypothesis that CD98hc is a regulator of HNSCC radioresistance. The ongoing experimental studies will reveal if CD98hc may be used as potential target for HNSCC radiosensitization.

Fragestellung: Das Mammakarzinom fasst eine heterogene Gruppe von Tumoren zusammen von denen etwa 20% als Triple-negativ (TNBC) bezüglich des Rezeptorstatus bezeichnet werden. Wichtige Parameter und therapeutische Angriffspunkte der TNBC Biologie sind eine hohe Proliferationsaktivität, ein Basal-artiger und mesenchymaler Phänotyp und ein Defekt im DNA Reparaturweg Homologe Rekombination (HR) welcher eine erhöhte chromosomale Instabilität dieser Tumore begünstigt. TNBCs weisen darüber hinaus eine Anreicherung von Tumorstammzellen und Therapieresistenz auf. Ziel des Projektes ist es Strategien unter gleichzeitiger Ausnutzung von HR-Defizienz und Stammzelleigenschaften durch spezifische Inhibition zur Intensivierung der Therapie weiter zu entwickeln. Dies wurde für die Inhibition von RAD51-, CHK1- und PARP1 nach Bestrahlung untersucht. Dafür wurde eine TNBC-Zelllinie (MDA-231 WT), zwei isogenen Sublinien, die präferentiell in Knochen (-SA) und Gehirn (-BR) metastasieren im Vergleich zu einer luminalen Zelllinie (MCF7) eingesetzt.
Methodik: In MDA-MB-231 WT/BR/SA und MCF7-Zellen wurde die Expression bezüglich HR (RAD51, BRCA1, PTEN, CHK1, MRE11, ATR, ATM) und Stammzelleigenschaften (ZEB1, E-Cadherin, ß-Catenin, ALDH1) charakterisiert, HR mittels RAD51-Foci, MMC-Sensitivität und Reporterplasmiden eingeordnet, Replikationsprozesse analysiert und die Migrationsfähigkeit überprüft. Strahlenempfindlichkeit wurde unter Gabe verschiedener Inhibitoren im Kolonietest dokumentiert und mit der Metabric Datenbank (952 TNBC) hinsichtlich des chromosomalen Instabilitätsindex (CIN) korreliert.
Ergebnisse: Es zeigten sich klare Unterschiede in der Expression von Reparaturproteinen, mit einem Anstieg von CHK1, MRE11 und ATM in BR und SA. Beide Linien zeigten Stammzell-übliche Expressionsprofile, entsprechend eine stärkere Migrationsfähigkeit und in der SA Linie eine verbesserte HR (2,5-fach), Resistenz gegen MMC (IC50 von 1,6µg/ml im Vergleich zu 0,75µg/ml in BR und 2,1 µg/ml in SA) und geringere DNA Schäden (0,75-fach). Nach Bestrahlung zeigte sich kein Überlebensvorteil für BR und SA. Dies deutet darauf hin, dass nicht HR, sondern übergeordnet CHK1-vermittelte Prozesse für die Strahlenempfindlichkeit verantwortlich sind. Bestätigt wird dies durch die deutliche Strahlensensitivierung nach CHK1i, wobei die strahlenresistenteste Linie sich am stärksten sensitivieren ließ, mit VF von 3. Dies spiegelt sich auch in den Replikationsprozessen wieder, je sensitiver, desto stärker inhibiert. Momentan wird der Einfluss weiterer Inhibitoren auf die zelluläre Strahlenempfindlichkeit überprüft. Topkandidat ist RAD51i, da in einer Metabric-Analyse TNBC mit hohem CIN, also besonders aggressiven Tumoren, RAD51 und CHK1 deutlich stärker exprimiert werden als in TNBCs mit niedrigem CIN.
Schlussfolgerung: Eine veränderte Expression von HR-Proteinen und ein Stammzell-artiger Phänotyp hängen eng zusammen und determinieren gemeinsam die Therapieresistenz.

Background: A major reprogramming of cellular energy metabolism is a hallmark of tumor cells. In addition to an increased glucose uptake, highly proliferative cancer cells require additional supplies for their biosynthesis and energy production such as glutamine. Glutaminolysis also contributes to the ROS scavenging and activation of the pro-survival signaling pathways. Tumors with enhanced MYC expression, such as prostate cancer have a particularly high demand for glutamine. Herein, we investigated the role of glutamine metabolism pathways for prostate cancer radioresistance. Methods: Prostate cancer cell lines DU145, PC3, LNCaP and their radioresistant sublines (RR) were analyzed by metabolomic and gene expression profiling. The relative cell sensitivity to the inhibition of glutaminolysis was measured by analysis of viability (MTT), apoptosis and necrosis (flow cytometry and Western blotting), levels of ROS and glutathione (flow cytometry), radiosensitivity (colony formation assay, CFA), DNA repair (γH2A.X foci) and tumorigenicity in mice. Primary cell cultures from 12 tumor biopsies and matched benign tissues from prostates cancer patients were characterized by radiobiological 3D CFA and by gene expression profiling, and relative radioresistance was correlated with expression levels of the genes regulating glutaminolysis. The Cancer Genome Atlas (TCGA) datasets were analyzed for correlation of the gene expression levels and patients outcome. Results: Glutaminolysis is upregulated in RR cells, where glutamine is mostly used for production of α-ketoglutarate, which is involved in ROS scavenging and epigenetic resetting by regulation of the histone methylation, whereas α-ketoglutarate utilization for Krebs cycle is suppressed. Deprivation of glutamine or siRNA mediated inhibition of glutaminolysis leads to the induction of endoplasmic reticulum (ER) stress and inhibition of the DNA repair, clonogenicity and in vivo tumorigenicity after irradiation with a more pronounced effect for RR cells. Analysis of the TCGA datasets revealed that a high expression of the genes regulating prostate cancer glutaminolysis is significantly associated with a decrease in relapse free survival after radiotherapy. Discussion: Prostate cancer cell radioresistance is associated with alterations of glutaminolysis, whose inhibition increases the cytotoxic effects of radiation in prostate tumor cells. Expression of the proteins involved in glutaminolysis can be potentially used to predict clinical outcome after radiation therapy.

Breast cancer comprises a heterogeneous group of tumors of whom 20% are categorized as triple-negative (TNBC). Important biological characteristics and potential therapeutic targets of TNBC include high proliferation, a basal-like and mesenchymal phenotype and a defect in the DNA repair pathway Homologous Recombination (HR), which feeds the observed elevated chromosomal instability in these tumors. TNBCs show an enrichment of cancer stem cells and therapy resistance. This project aims to develop treatment intensification strategies based on the simultaneous exploitation of the HR-deficiency and the stem-like phenotype, using specific inhibitors for RAD51, CHK1 and PARP1 in combination with irradiation.
Expression of HR-related (RAD51, BRCA1, PTEN, CHK1, MRE11, ATR, ATM) and stem-like factors (ZEB1, E-Cadherin, ß-Catenin, ALDH1) as well as HR functionality (via RAD51 foci, MMC-sensitivity and plasmid reporter assay) were determined in the TNBC line MDA-231 WT, its two sublines preferentially metastasizing to brain (BR) or bone (SA) and in the luminal BC line MCF7. DNA replication (fiber assay) and migration assay were also tested. Radiosensitivity and the radiosensitizing effect of different inhibitors was analyzed by colony assay and correlated to the CIN in the METABRIC database.
Distinct differences in the expression of HR-related proteins were observed, with an elevated expression of CHK1, MRE11 and ATM in BR and SA relative to WT and MCF7. BR and SA showed a typical stem cell-like protein expression profile, together with a higher migration capacity, increased HR-capacity, resistance against MMC and less DNA damage. After irradiation no advantage in survival for the BR and SA cell lines was observed, suggesting that not HR, but superordinate CHK1 signaling promotes radioresistance. This was confirmed by a distinct radiosensitization after CHK1i; the most radioresistant WT cell line was most strongly sensitized, by a factor of 3. The extent of sensitization was also linked to the extent of replication inhibition. The effect of other inhibitors on radiosensitivity is currently being investigated. A second promising target is RAD51, because a METABRIC analysis (952 TNBCs) showed that in TNBC with high CIN RAD51 and CHK1 are significantly stronger expressed than in TNBC with low CIN.
In conclusion the results presented here show that DNA repair and a stem-like phenotype collude to determine resistance to tumor therapy of TNBCs with high CIN.

no abstract available

Identification and quantification of nanoparticulate materials in living and non-living media is mandatory for a thorough nanosafety research. However, the online and in-situ monitoring of nanoparticles in such complex natural systems as soil, natural waters, plants, sewage sludge, etc. is highly challenging, especially at environmentally relevant concentrations. Radiolabeling offers a robust method for these complex studies within a wide range concentration of nanoparticles even in the presence of background concentrations of the respective elements.

Depending on the nature of the nanoparticle and the process of interest we applied different methods for the radiolabeling of common nanoparticles, like the synthesis of the nanoparticles using radioactive starting materials, the binding of the radiotracer to the nanoparticles, the activation of the nanoparticles using proton irradiation, the recoil labeling utilizing the recoil of a nuclear reaction to implant a radiotracer into the nanoparticle, and the in-diffusion of radiotracers into the nanoparticles.

For our recent studies we produced [¹⁰⁵Ag]Ag, [^110mAg]Ag, [⁴⁴Ti]TiO₂, [⁴⁵Ti]TiO₂, [⁴⁸V]TiO₂, [⁶⁴Cu]CuS, [⁶⁴Cu]SiO₂, [⁶⁵Zn]CdSe/ZnS, [¹²⁴I]CNTs, [¹²⁵I]CNTs, [¹³¹I]CNTs, [⁷Be]MWCNT, [¹³⁹Ce]CeO₂ and [¹⁹⁴Au]Pt nanoparticles (including radiolabeled commercial nanoparticle samples). Due to the choice of the used radionuclide (half-life, decay-mode) and the activity concentrations it was possible to enable different detection methods and time scales for the investigations. All these methods go along with a careful characterization of the radiolabeled nanoparticles in respect of the radiolabeling stability and nanoparticle properties.

The radiolabeled nanoparticles can easily be detected down to ng/L range and have been successfully used in investigations of the uptake of nanoparticles in plants, the distribution and mobility of nanoparticles in sewage sludge, fate of nanoparticles in wastewater treatment processes and in release studies.

Background
The interplay effect might degrade the dose of pencil beam scanning proton therapy to a degree that free-breathing treatment might be impossible without further motion mitigation techniques, which complicate and prolong the treatment. We assessed whether treatment of free-breathing patients without motion mitigation is feasible.
Material/Methods
For 40 lung cancer patients, 4DCT datasets and individual breathing patterns were used to simulate 4D dynamic dose distributions of 3D treatment plans over 33 fractions delivered with an IBA universal nozzle. Evaluation was done by assessing under- and overdosage in the target structure using the parameters V90, V95, V98, D98, D2, V107 and V110. The impact of using beam-specific target volumes and the impact of changes in motion and patient anatomy in control 4DCTs were assessed.
Results
Almost half of the patients had tumour motion amplitudes of less than 5mm. Under- and overdosage was significantly smaller for patients with tumour motion below 5mm compared to patients with larger motion (2% versus 13% average absolute reduction of V95, 2% versus 8% average increase in V107, p<0.01). Simulating a 33-fraction treatment, the dose degradation was reduced but persisted for patients with tumour motion above 5mm (average ΔV95 of <1% vs 3%, p<0.01). Beam-specific target volumes reduced the dose degradation in a fractionated treatment, but were more relevant for large motion. Repeated 4DCT revealed that changes in tumour motion during treatment might result in unexpected large dose degradations.
Conclusion
Tumour motion amplitude is an indicator of dose degradation caused by the interplay effect. Fractionation reduces the dose degradation allowing the unmitigated treatment of patients with small tumour motions of less than 5mm. The beam-specific target approach improves the dose coverage. The tumour motion and position needs to be assessed during treatment for all patients, to quickly react to possible changes which might require treatment adaptation.

Elastic Recoil Detection Analysis (ERDA) is a near-surface heavy ion beam based elemental characterization technique, known especially for its suitability for light element analysis of thin films. The elemental composition of an unknown sample can be determined quantitatively in a single measurement, without resorting to the use of standards or information from additional measurements or models.

In the Ion Beam Center (IBC) of the Helmholtz-Zentrum Dresden-Rossendorf a Bragg Ionization Chamber (BIC) based ERDA setup has been operated successfully for many years. In the past there has also been a time-of-flight telescope installed in the same chamber. During 2017 this instrument will be upgraded with new detectors, bringing it up to date with latest experimental developments in the field.

The goal for the project is first and foremost to construct a user-friendly instrument, which can be operated reliably. Special emphasis will be put to the achievable depth resolution, without sacrificing performance in other areas. The instrument can be operated with a relatively broad energy range, with lower incident beam energy (< 10 MeV) enabling high depth resolution (2 nm) near the surface and higher energies, e.g. 20 MeV, enable excellent mass separation and better probing depth for thicker films.

In this contribution we will present the basic idea of the new setup and give some particular details on the design, expected performance and a realization time line.

The 14N(p,γ)15O reaction is the slowest reaction of the carbon-nitrogen cycle of hydrogen burning and thus determines its rate. The precise knowledge of its rate is required to correctly model hydrogen burning in asymptotic giant branch stars. In addition, it is a necessary ingredient for a possible solution of the solar abundance problem by using the solar 13N and 15O neutrino fluxes as probes of the carbon and nitrogen abundances in the solar core. After the downward revision of its cross section due to a much lower contribution by one particular transition, capture to the ground state in 15O, the evaluated total uncertainty is still 8%, in part due to an unsatisfactory knowledge of the excitation function over a wide energy range. The present work reports precise S-factor data at twelve energies between 0.357-1.292 MeV for the strongest transition, capture to the 6.79 MeV excited state in 15O, and at ten energies between 0.479-1.202 MeV for the second strongest transition, capture to the ground state in 15O. A simple R-matrix fit is performed to gauge the impact of the new data on astrophysical energies. The recently suggested slight enhancement of the ground state transition at low energy could not be confirmed. The present extrapolated zero-energy S-factors are S679(0) = 1.24±0.11 keVbarn and SGS(0) = 0.19±0.06 keVbarn.