Publication database - Helmholtz-Zentrum Dresden-Rossendorf

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27573 Publications
Entwicklung und Validierung von Bildauswertealgorithmen zur Charakterisierung der Gas-Flüssigkeits-Strömung in Anstaupackungen
Litzka, A.
Abstract: Am Helmholtz-Zentrum Dresden Rossendorf wird die Fluiddynamik von Anstaupackungen untersucht, einer neuen Form von Einbauten für Trennkolonnen. Für die Auswertung der Messungen mithilfe der ultraschnellen Röntgentomographie werden Algorithmen benötigt, welche die Ermittlung der Phasenverteilung in den Packungen ermöglichen.
In dieser Arbeit wurde untersucht, ob dies mithilfe von Bildsegmentierung erfolgen kann. Die Segmentierung muss in Gas, Flüssigkeit und Titanblech erfolgen. Es wurden geeignete Messphantome erstellt, anhand derer die Implementierung der Algorithmen erfolgte. Für die Validierung der Ergebnisse wurden Referenzmessungen mit Röntgen-Mikrotomographie eingesetzt.
Aufgrund der mangelnden Bildqualität der rekonstruierten Daten ist zunächst nur Identifikation der Gasphase in den Phantomen möglich. Der Ansatz die Feststoffstruktur mithilfe der Referenzmessung lokalisieren zu können, scheiterte an einer Verzerrung der abgebildeten Geometrien durch die ultraschnelle Röntgentomographie infolge der Bildrekonstruktion.
Des Weiteren wurde versucht mithilfe einer Dekonvolution die Bildqualität zu verbessern und so die Voraussetzung für eine Segmentierung in drei Phasen zu schaffen. Im entfalteten Bild ist es für eine der drei Strömungsformen möglich, in lokalen Bereichen Schwellwerte für eine Segmentierung in drei Phasen zu ermitteln. Offen ist, ob sich dies auf die anderen Strömungsformen übertragen lässt und eine Optimierung der Auswertealgorithmen eine ausreichende Genauigkeit der Anteilsbestimmung ermöglicht.
  • Study thesis
    TU Dresden, 2017
    Mentor: J. Sohr, M. Schubert, U. Hampel
Registration No. 25285 - Permalink

Untersuchung heterogener Strömungsmuster in Anstaupackungen mittels ultraschneller Röntgentomographie: Methode und Validierung
Sohr, J.; Litzka, A.; Schubert, M.; Flechsig, S.; Kenig, E. Y.; Hampel, U.
Abstract: Die Kombination von strukturierten Packungen unterschiedlicher geometrischer Oberflächen in Anstaupackungen (s. Abb. 1) führt zu einem axial verteilten Strömungsprofil bestehend aus Blasenströmung, Sprudelschicht und Filmströmung. Die Strömungsmorphologie variiert dabei in den einzelnen Strömungsbereichen sehr stark, sodass durch integrale Hold-up-Messungen kaum Rückschlüsse auf die individuellen Flüssigkeitsinhalte und Phasengrenzflächen gezogen werden können. Zeitlich und örtlich hochaufgelöste bildgebende Messverfahren, wie die ultraschnelle Röntgentomographie, können hier neue Erkenntnisse zur Fluiddynamik liefern [1].
Im Rahmen eines durch die DFG geförderten Projekts sind umfangreiche Fluiddynamikstudien mittels ultraschneller Röntgentomographie geplant. In einem ersten Schritt wird die ultraschnelle Röntgentomographie für die Untersuchung der unterschiedlichen Strömungsmorphologien validiert. Dazu werden mittels Micro-Computertomographie exakt charakterisierte statische Messphantome eingesetzt und Methoden zur Erfassung und Bewertung von Hold-up, Phasenverteilung und Phasengrenzflächen entwickelt. Die Validierung dieser Methoden ist Gegenstand dieses Beitrags.
[1] Janzen, A., Schubert, M., Barthel, F., Hampel, U., Kenig, E.Y., Chem. Eng. Process, (2013), 66, 20-26.
  • Lecture (Conference)
    Jahrestreffen der ProcessNet Fachgruppen Mechanische Flüssigkeitsabtrennung, Kristallisation, Phytoextrakte, Adsorption, Extraktion, Fluidverfahrenstechnik und Membrantechnik, 06.-10.03.2017, Köln, Deutschland
Registration No. 25283 - Permalink

The photoluminescence response to structural changes of Yb implanted ZnO crystals subjected to non-equilibrium processing
Ratajczak, R.; Prucnal, S.; Guziewicz, E.; Mieszczynski, C.; Snigurenko, D.; Stachowicz, M.; Skorupa, W.; Turos, A.
Abstract: In this paper, we present the detailed study of optical and structural properties of Yb implanted single ZnO crystals. Hydrothermally grown wurtzite (0001) ZnO crystals were implanted with 150 keV Yb ions to fluencies of 5e14 and 1e15 at/cm2. After ion implantation, two different types of annealing were performed: rapid thermal annealing (RTA) and millisecond range flash lamp annealing (FLA). Crystalline quality, damage recovery, and Yb lattice site location were evaluated by the Channeling Rutherford Backscattering Spectrometry (RBS/c). It is shown that independent of the used annealing technique, defects formed in ZnO during ion implantation can be removed. Upon RTA performed at the temperature higher than 800C, strong out-diffusion of implanted Yb atoms and precipitation on the surface takes place. Consequently, the degradation of the photoluminescence (PL) efficiency is observed. The diffusion of implanted Yb during millisecond range FLA does not occur for such experimental conditions. Moreover, FLA treatment for 20 ms leads to the formation of single crystalline ZnO layer with Yb incorporated in the substitutional lattice sites. According to RBS/c and PL data, Yb atoms substituted in the Zn sublattice are predominantly in the 2þ oxidation state. The most intensive PL has been observed after annealing at 800C for 20 min which is accompanied with the reduction of Yb substitutional fraction and formation of octahedron Yb-oxygen clusters within ZnO.
Keywords: ZnO, ion implantation, FLA, Yb, photoluminescence, RBS Registration No. 25279 - Permalink

Architecture and mineral potential of the Paleoproterozoic Karrat Group, West Greenland: Results of the 2016 Season
Rosa, D.; Dewolfe, M.; Guarnieri, P.; Kolb, J.; Laflamme, C.; Partin, C. A.; Salehi, S.; Sørensen, E. V.; Thaarup, S.; Thrane, K.; Zimmermann, R.
Abstract: This report presents the preliminary results of the second field season of a joint project be- tween the Geological Survey of Denmark and Greenland (GEUS) and the Ministry of Min- eral Resources of Greenland (MMR) focusing on the Paleoproterozoic Karrat Group. The motivation for the expedition stems from an evaluation of the mineral potential along with understanding the stratigraphic architecture of the Karrat Group and aims to address stra- tigraphy, structure, and economic geology. Field work extended to northern Karrat Group outcrops, between Upernavik and Kullosuaq, and allowed further studies of the southern Karrat Group outcrops between Svartenhuk and Maarmorilik. The relationship between the Karrat Group and the Prøven Igneous Complex (PIC), emplaced between these two areas, was also assessed. The 2016 field season was aided by oblique aerial photography (“pho- toflying”), and hyperspectral techniques. Hyperspectral scenes were collected along cliff faces in the areas with the most prospective mineral potential, including Kangerluarsuk Fjord and Maarmorilik. These studies have built on the observations made in 2015, and have led either to the consolidation or to the revision of interpretations suggested after that season.
The exposed Karrat Group extends from ~71° to ~75°N and is composed of five formations: the Qeqertarssuaq (Lower Karrat Group), Qaarsukassak, Mârmorilik, Kangilleq, and Nûkavsak formations (Upper Karrat Group), of which the Qaarsukassak amd Kangilleq formations are informal. The lower and upper Karrat Group are separated by a regional erosional unconformity, which represents a revision to the Karrat stratigraphy established during the 2015 field season. The Karrat Group has not been differentiated north of Uper- navik due to the high metamorphic grade and polyphase deformation. Major goals of the field work included delineating contact relationships between units, documenting sedimen- tary structures that can define depositional environment(s), mapping the lateral extent and nature of extrusive mafic volcanism and volcaniclastic rocks in the upper Karrat Group (Kangilleq Formation), and determining the relative age relationships between units, which is elusive since several units are not in contact with one another. Integrated stratigraphy, sedimentology, volcanology, and ongoing geochronology will lead to a better understanding of the basin tectonic setting(s) in which the Karrat Group was deposited.
The deformation history of the area put forward after the 2015 season has been reviewed, and this succession is suggested: a NW-vergent D1 north of the Prøven Igneous Complex and channel flow in an orogen-scale NW-SE compression; D2 is characterised by E-W extension near Archean orthogneiss at Kangiusap Kuua and distal compression further to the E (previously assigned to D4); D3 is represented by structuring of the Kigarsima nappe overprinting all the other structures on Karrat Island and the peninsula to the SE (formerly described as D2); and, finally, a NW-SE compression, documented in the Maarmorilik area, is now relabeled as D4 (previously assigned to D3).
The time-stratigraphic horizon above and laterally to the Kangilleq Formation volcanism represents a period of VMS-formation on (or just below) the seafloor. Sampling of massive sulfides has yielded anomalous base metal concentrations (typically <0.3% Cu+Pb+Zn). However, because it is known that massive sulfide horizons can display zonations from low-grade to gold- and/or base metal-rich zones, these horizons potentially constitute tar- gets for future base metal and/or gold exploration in the Karrat region.
A Mississippi-Valley Type (MVT) origin is suggested for the Zn-Pb mineralisation in the Qaarsukassak Formation (RTZ Discovery), which might therefore have formed at the same time as the mineralisation in the Mârmorilik Formation. This is based on proximity of the Qaarsukassak Formation mineralisation to Archean rocks and the association of its distri- bution with marble and chert horizons. The possible role of evaporites and their diapirism in the mineralising process has been highlighted in the Mârmorilik Formation, by establishing the proximity of the known Lower Mârmorilik Formation showings to what can be interpret- ed to have been an evaporite horizon (now a “mottled pelite”). From this horizon, evaporites possibly ascended and were emplaced, as diapirs, within the Upper Mârmorilik Formation, underneath the pelites that would have acted as cap rock (where the Black Angel deposit is). Diapirism was likely triggered by deformation, during which evaporites flowed along thrust planes, as has been tentatively documented through the hyperspectral survey.
Possible silicate-silicate liquid immiscibility accompanied by silicate-sulfide immisciblity, occurred in a gabbro complex identified on the eastern side of Nutaarmiut island, to the southeast of Upernavik. The degree of PGE-Au enrichment in the sulfide has not been tested yet, but could potentially be of economic significance.
  • Other report
    København: GEUS Geological Survey of Denmark and Greenland, 2017
    112 Seiten
Registration No. 25270 - Permalink

Validation and update of the baseline model for poly-disperse bubbly flows
Lucas, D.; Krepper, E.; Rzehak, R.; Ziegenhein, T.; Ma, T.; Liao, Y.
Abstract: For the consolidation of CFD-methods basing on the multi-fluid approach a baseline model strategy has been developed. Following this strategy a baseline model for poly-disperse bubbly flows was recently defined. This model is presented and an overview on the status as well as selected examples for the validation are given. Furthermore new developments regarding bubble induced turbulence, lateral lift force and bubble coalescence and breakup modelling are presented.
Keywords: baseline model, bubbly flow, CFD, bubble induced turbulence, lateral lift force, coalescence, breakup
  • Lecture (Conference)
    28th Meeting of the German CFD Network of Competence, 07.03.2017, Garching, Deutschland
Registration No. 25262 - Permalink

Scalable, multi-GPU photon tracing for in-situ X-ray radiation transport in solid density plasmas
Garten, M.ORC; Grund, A.; Huebl, A.; Burau, H.; Widera, R.; Kluge, T.; Fortmann-Grote, C.; Bussmann, M.
Abstract: We present our scientific roadmap towards in-situ modeling of non-LTE interactions of XFEL type X-rays with solid density plasmas using a symbiosis of our performance portable, open source, 3D3V particle-in-cell (PIC) code PIConGPU and its X-ray tracing prototype ParaTAXIS. Treating radiation transport via various atomic processes will enable us to synthesize detector signals and gain predictive capabilities for upcoming pump-probe experiments at the European XFEL. With the world’s fastest particle-in-cell code PIConGPU and the raw computational power of the largest high performance computers we open up the possibility for large-scale case studies of unprecedented repeatability.
Keywords: ParaTAXIS, PIConGPU, radiation transport, plasma physics, atomic processes
  • Poster
    2017 Joint ICTP-IAEA School on Atomic Processes in Plasmas, 27.02.-03.03.2017, Trieste, Italia
Registration No. 25245 - Permalink

Annual Report 2016 Institute of Resource Ecology
Stumpf, T.; Foerstendorf, H.ORC; Bok, F.; Richter, A.
Abstract: The Institute of Resource Ecology (IRE) is one of the eight institutes of the Helmholtz-Zentrum Dresden – Rossendorf (HZDR). The research activities are mainly integrated into the program “Nuclear Waste Management, Safety and Radiation Research (NUSAFE)” of the Helmholtz Association (HGF) and focused on the topics “Safety of Nuclear Waste Disposal” and “Safety Research for Nuclear Reactors”...
  • Wissenschaftlich-Technische Berichte / Helmholtz-Zentrum Dresden-Rossendorf; HZDR-079 2017
    ISSN: 2191-8708

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Registration No. 25236 - Permalink

A novel nanobody-based target module for retargeting of T lymphocytes to EGFR-expressing cancer cells via the modular UniCAR platform
Albert, S.; Arndt, C.; Feldmann, A.; Bergmann, R.; Bachmann, D.; Koristka, S.; Ludwig, F.; Ziller-Walter, P.; Kegler, A.; Gärtner, S.; Schmitz, M.; Ehninger, A.; Cartellieri, M.; Ehninger, G.; Pietzsch, H.-J.; Pietzsch, J.; Steinbach, J.; Bachmann, M.
Abstract: Recent treatments of leukemias with chimeric antigen receptor (CAR)-expressing T cells underline their impressive therapeutic potential. However, once adoptively transferred into patients, there is little scope left to shut them down after elimination of tumor cells or in case adverse side effects occur. This becomes of special relevance if they are directed against commonly expressed tumor associated antigens (TAAs) such as receptors of the ErbB family. To overcome this limitation, we recently established a modular CAR platform technology termed UniCAR. UniCARs are not directed against TAAs but instead against a unique peptide epitope on engineered recombinant targeting modules (TMs) which guide them to the target. In the absence of a TM UniCAR T cells are inactive. Thus an interruption of any UniCAR activity requires an elimination of unbound TM and the TM complexed with UniCAR T cells. Elimination of the latter one requires a disassembly of the UniCAR-TM complexes. Here we describe a first nanobody (nb)-based TM directed against EGFR. The novel TM efficiently retargets UniCAR T cells to EGFR positive tumors and mediates highly efficient target-specific and target-dependent tumor cell lysis both in vitro and in vivo. After radiolabeling of the novel TM with 64Cu and 68Ga we analyzed its biodistribution and clearance as well as the stability of the UniCAR-TM complexes. As expected unbound TM is rapidly eliminated while the elimination of the TM complexed with UniCAR T cells is delayed. Nonetheless, we show that UniCAR-TM complexes dissociates in vitro and in vivo in a concentration-dependent manner in line with the concept of a repeated stop and go retargeting of tumor cells via the UniCAR technology.
Keywords: CAR, EGFR, Retargeting, T cell, T cell therapy Registration No. 25222 - Permalink

Li, Co, Nd ... - Strategische Metalle für die Elektromobilität
Rudolph, M.ORC
Abstract: Elektromobilität ist zurzeit in aller Munde; von eAutos, eBikes und Pedelecs hat jeder schon gehört. Die 32. Hochschultage Physik widmen sich dem gegenwärtigen Stand der Technik und der Zukunft dieses spannenden Forschungsgebietes. Vortragende aus Wissenschaft und Industrie greifen ein breites Spektrum an Aspekten auf, das sicherlich Anregungen für lebhafte Diskussionen bietet.
Die Veranstaltung richtet sich nicht nur an Lehrerinnen und Lehrer, sondern auch an die breite Öffentlichkeit, an Studierende und natürlich auch an die Mitglieder des Fachbereichs Physik.
  • Invited lecture (Conferences)
    32. Hochschultage Physik, 13.-14.02.2017, Marburg, Deutschland
Registration No. 25216 - Permalink

Als Ingenieur in der Forschung - an der Grenzfläche von Wissenschaft, Gesellschaft und Anwendung
Rudolph, M.ORC
Abstract: Ingenieure sind vielseitige Problemlöser und daher sehr gefragt in der Forschung, sowohl in Industrie wie auch in der Wissenschaft. Noch bis ins 19. Jahrhundert aber waren Ingenieure nicht wirklich geduldet als Wissenschaftler, nicht ohne Grund ist der Doktorgrad der Ingenieurwissenschaften in Deutschland seit dem als einziger nicht lateinisch und versehen mit einem Bindestrich, also Dr.-Ing. und nicht Dr. rer. tech. Der moderne Ingenieur ist aber schon längst ein angewandter Naturwissenschaftler und nicht nur geschickter Tüftler. Der Beitrag soll anhand der eigenen Erfahrungen des Vortragenden einen Einblick geben über die spannenden Themen eines Ingenieurs in der Forschung. Ganz speziell werden darüber hinaus die Felder der Grenzflächenverfahrenstechnik und der Ressourcentechnologie vorgestellt und aufgegriffen. Dabei soll auch das Spannungsfeld aus Wissenschaft, Gesellschaft und Anwendung beleuchtet werden.
  • Invited lecture (Conferences)
    VDI suj Freiberg - Stammtisch, 09.01.2017, Freiberg, Deutschland
Registration No. 25215 - Permalink

Uranium mining, resulting ecological problems and references to spectroscopic methods
Baumann, N.
Abstract: 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.
Keywords: uranium, speciation, migration and sorption behavior, TRLFS, EXAFS
  • Invited lecture (Conferences)
    Invited presentation, 03.03.2017, Sriracha, Thailand
Registration No. 25209 - Permalink

Analysis for Optimum Conditions for Recovery of Valuable Metals from E-waste Through Black Copper Smelting
Reuter, M. A.; Rhamdhani, M. A.; Brooks, G. A.; Masood, S.; Shuva, M. A. H.; Firdaus, M.
Abstract: 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.
Keywords: Resources efficiency E-waste Black copper Metal recovery
  • Book chapter
    Hwang, Jiang, Kennedy, Yücel, Pistorius; Seshadri, Zhao, Gregurek; Keskinkilic: Analysis for Optimum Conditions for Recovery of Valuable Metals from E-waste Through Black Copper Smelting, New York: Springer International Publishing, 2017, 978-3-319-51339-3, 419-427
    DOI-Link: http://dx.doi.org/10.1007/978-3-319-51340-9_41
Registration No. 25205 - Permalink

Individualized early death and long-term survival prediction after stereotactic radiosurgery for brain metastases of non-small cell lung cancer: Two externally validated nomograms
Zindler, J.; Jochems, A.; Lagerwaard, F.; Beumer, R.; Troost, E.; Eekers, D.; Compter, I.; van der Toorn, P.-P.; Essers, M.; Oei, B.
Abstract: 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.

Keywords: Individualized brain metastases Stereotactic radiosurgery Prognostic models Registration No. 25204 - Permalink

PIConGPU the 3D3V Particle-in-Cell Code Developed at HZDR – A Status Update
Huebl, A.ORC; Garten, M.; Pausch, R.; Matthes, A.; Branco, J.; Steiniger, K.; Burau, H.; Grund, A.; Debus, A.; Kluge, T.; Widera, R.; Bussmann, M.
Abstract: 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.

Keywords: Simulation, LPA, PIC, PIConGPU, FLOSS, Open Source, Modeling, Synthetic Diagnostics
  • Lecture (Conference)
    Third MT student retreat, Third Annual Matter & Technologies Meeting, 30.-31.01.2017, Darmstadt, Germany
Registration No. 25203 - Permalink

Proton implantation for electrical insulation of the InGaAs/InAlAs superlattice material used in 8–15 μm-emitting quantum cascade lasers
Kirch, J. D.; Kim, H.; Boyle, C.; Chang, C.-C.; Mawst, L. J.; Lindberg Iii, D.; Earles, T.; Botez, D.; Helm, M.; von Borany, J.; Akhmadaliev, S.; Böttger, R.; Reyner, C.
Abstract: 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.
Keywords: Quantum cascade lasers, Ion Implantation, Protons, Superlattices, Leakage currents, Carrier mobility Registration No. 25201 - Permalink

Our strategic approach: Reactive transport modelling based on parameters obtained from batch and GeoPET column experiments: example from leaching of a fractured drill core
Karimzadeh, L.; Kulenkampff, J.; Schymura, S.; Eichelbaum, S.; Lippmann-Pipke, J.
Abstract: 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.

Keywords: Reactive transport modeling, GeoPET, In-situ leaching, iCP
  • Invited lecture (Conferences)
    7th Reactive Transport PhD Workshop, 23.02.2017, Leipzig, Germany
Registration No. 25200 - Permalink

Comparison of toxicity and outcome in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy using IMRT or VMAT
Wijsman, R.; Dankers, F.; Troost, E. G. C.; Hoffmann, A. L.; van der Heijden, E. H. F. M.; de Geus-Oei, L. F.; Bussink, J.
Abstract: 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.
Keywords: Non-small cell lung cancer Intensity-modulated radiation therapy Volumetric-modulated radiation therapy Toxicity
  • Radiotherapy and Oncology 122(2017)2, 10.1016/j.radonc.2016.11.015
    Button zum Volltext
Registration No. 25196 - Permalink

Holographic QCD phase diagram with critical point from Einstein-Maxwell-dilaton dynamics
Knaute, J.; Yaresko, R.; Kämpfer, B.
Abstract: 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.

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Registration No. 25195 - Permalink

The Beautiful Molecule: 30 Years of C60 and its Derivatives
Acquah, S. F. A.; Penkova, A. V.; Markelov, D. A.; Semisalova, A. S.; Leonhardt, B. E.; Magi, J. M.
Abstract: 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.

Keywords: Fullerene, fullerenol, metallofullerenes, mechanical properties, electrical properties

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Registration No. 25193 - Permalink

Prediction of countercurrent flow limitation and its uncertainty in horizontal and slightly inclined pipes
Murase, M.; Utanohara, Y.; Kusunoki, T.; Yamamoto, Y.; Lucas, D.; Tomiyama, A.
Abstract: 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.
Keywords: PWR hot leg, pressurizer surge line, countercurrent flow limitation Registration No. 25189 - Permalink

Determination of N* excitation functions in associated strangeness production in p+p collisions
Münzer, R.; Fabbietti, L.; Epple, E.; Lu, S.; Klose, P.; Hauenstein, F.; Herrmann, N.; Grzonka, D.; Leifels, Y.; Maggiora, M.; Pleiner, D.; Ramstein, B.; Ritman, J.; Roderburg, E.; Salabura, P.; Sarantsev, A.; Basrak, Z.; Buehler, P.; Cargnelli, M.; Caplar, R.; Czerwiakowa, O.; Deppner, I.; Dzelalija, M.; Fodor, Z.; Gasik, P.; Gasparic, I.; Grishkin, Y.; Hartmann, O. N.; Hildenbrand, K. D.; Hong, B.; Kang, T. I.; Kecskemeti, J.; Kim, Y. J.; Kirejczyk, M.; Kis, M.; Koczon, P.; Kotte, R.; Lebedev, A.; Le Fevre, A.; Liu, J. L.; Manko, V.; Marton, J.; Matulewicz, T.; Piasecki, K.; Rami, F.; Reischl, A.; Ryu, M. S.; Schmidt, P.; Seres, Z.; Sikora, B.; Sim, K. S.; Siwek-Wilczynska, K.; Smolyankin, V.; Suzuki, K.; Tyminski, Z.; Wagner, P.; Weber, I.; Widmann, E.; Wisniewski, K.; Xiao, Z. G.; Yamasaki, T.; Yushmanov, I.; Zhang, Y.; Zhilin, A.; Zinyuk, V.; Zmeskal, J.
Abstract: 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.

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Registration No. 25177 - Permalink

Low CSC marker expression and low hypoxia identify good prognosis subgroups in HPV(-)HNSCC after postoperative radiochemotherapy: a multicenter study of the DKTK-ROG
Linge, A.; Löck, S.; Gudziol, V.; Nowak, A.; Lohaus, F.; von Neubeck, C.; Jütz, M.; Abdollahi, A.; Debus, J.; Tinhofer, I.; Budach, V.; Sak, A.; Stuschke, M.; Balermpas, P.; Rödel, C.; Avlar, M.; Grosu, A. L.; Bayer, C.; Belka, C.; Pigorsch, S.; Combs, S. E.; Welz, S.; Zips, D.; Buchholz, F.; Aust, D. E.; Baretton, G. B.; Thames, H. D.; Dubrovska, A.; Alsner, J.; Overgaard, J.; Baumann, M.; Krause, M.; DKTK-RTOG
Abstract: Purpose: To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Experimental Design: Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control.

Results: Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P = 0.010) or the 26-gene signature (P = 0.002). In multivariate analyses, in patients with HPV16 DNA–negative but not with HPV16 DNA–positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P = 0.006; 26-gene signature: HR 10.27, P = 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P = 0.016; SLC3A2: HR 8.54, P = 0.037; CD44: HR 3.36, P = 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA–negative subgroup.

Conclusions: We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA–negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies.
Registration No. 25163 - Permalink

3D matrix-based cell cultures: Automated analysis of tumor cell survival and proliferation
Eke, I.; Hehlgans, S.; Sandfort, V.; Cordes, N.
Abstract: 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.
  • International Journal of Oncology 48(2016)1, 313-321
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Registration No. 25162 - Permalink

Comparison of toxicity and outcome in stage III NSCLC patients treated with IMRT or VMAT
Wijsman, R.; Dankers, F.; Troost, E. G. C.; Hoffmann, A. L.; Bussink, J.
  • Abstract in refereed journal
    Radiotherapy and Oncology 119(2016)Suppl.1, S317
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Registration No. 25161 - Permalink

beta1 Integrin/JNK Wechselwirkung im Glioblastom: Radiochemosensibilisierung und Invasionshemmung
Vehlow, A.; Klapproth, E.; Storch, K.; Matzke, D.; Cordes, N.
  • Abstract in refereed journal
    Strahlentherapie und Onkologie 192(2016)Suppl.1, 75
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Registration No. 25160 - Permalink

The potential of radiomics for radiotherapy individualization
Troost, E. G. C.; Pilz, K.; Löck, S.; Leger, S.; Richter, C. Registration No. 25159 - Permalink

Three-dimensional ECM-based cell culture models for cancer research
Storch, K.; Dickreuter, E.; Vehlow, A.; Cordes, N.
  • Abstract in refereed journal
    European Journal of Cancer 61(2016)Suppl.1, S74
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Registration No. 25158 - Permalink

Gene signatures predict loco-regional control after postoperative radiochemotherapy in HNSCC
Schmidt, S.; Linge, A.; Lohaus, F.; Gudziol, V.; Nowak, A.; Tinhofer, I.; Budach, V.; Sak, A.; Stuschke, M.; Balermpas, P.; Rödel, C.; Avlar, M.; Grosu, A. L.; Abdollahi, A.; Debus, J.; Belka, C.; Pigorsch, S.; Combs, S. E.; Mönnich, D.; Zips, D.; Baretton, G. B.; Buchholz, F.; Baumann, M.; Krause, M.; Löck, S. Registration No. 25157 - Permalink

MRI imaging of irradiated liver tissue for in vivo verification in particle therapy
Richter, C.; Duda, D. G.; Guimaraes, A. R.; Hong, T. S.; Bortfeld, T. R.; Seco, J.
  • Abstract in refereed journal
    Radiotherapy and Oncology 119(2016)Suppl.1, S51-S52
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Registration No. 25156 - Permalink

The variability of the RBE in proton therapy: can we base it on empirical clinical data?
Lühr, A.; von Neubeck, C.; Baumann, M.; Krause, M.
  • Abstract in refereed journal
    Radiotherapy and Oncology 119(2016)Suppl. 1, S417
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Registration No. 25155 - Permalink

Impact of tumour hypoxia and cancer stem cells on loco-regional control after primary radiochemotherapy in locally advanced HNSCC – results of a multicentre biomarker study of the German Cancer Consortium radiation Oncology Group
Linge, A.; Lohaus, F.; Löck, S.; Gudziol, V.; Nowak, A.; von Neubeck, C.; Tinhofer, I.; Budach, V.; Sak, A.; Stuschke, M.; Balermpas, P.; Rödel, C.; Avlar, M.; Grosu, A. L.; Abdollahi, A.; Debus, J.; Bayer, C.; Belka, C.; Pigorsch, S.; Combs, S. E.; Mönnich, D.; Zips, D.; Baretton, G. B.; Buchholz, F.; Baumann, M.; Krause, M.
  • Abstract in refereed journal
    Oncology Research and Treatment 39(2016)Suppl.1, 22-23
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Registration No. 25150 - Permalink

Tumour volume, hypoxia and cancer stem cells as prognosticators for LRC after primary RCT in HNSCC
Linge, A.; Lohaus, F.; Löck, S.; Gudziol, V.; Nowak, A.; von Neubeck, C.; Tinhofer, I.; Budach, V.; Sak, A.; Stuschke, M.; Balermpas, P.; Rödel, C.; Avlar, M.; Grosu, A. L.; Abdollahi, A.; Debus, J.; Belka, C.; Pigorsch, S.; Combs, S. E.; Mönnich, D.; Zips, D.; Baretton, G. B.; Buchholz, F.; Baumann, M.; Krause, M. Registration No. 25149 - Permalink

Comparison of machine-learning methods for predictive radiomic models in locally advanced HNSCC
Leger, S.; Bandurska-Luque, A.; Pilz, K.; Zöphel, K.; Baumann, M.; Troost, E. G. C.; Löck, S.; Richter, C. Registration No. 25147 - Permalink

Hypoxie und Krebsstammzellmarker als Biomarker für die Radio(chemo)therapie von Kopf-Hals Plattenepithelkarzinomen
Krenn, C.; Linge, A.; Lohaus, F.; Löck, S.; Baumann, M.; Krause, M.
  • Abstract in refereed journal
    Strahlentherapie und Onkologie 192(2016)Suppl.1, 121-122
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Registration No. 25146 - Permalink

beta1-Integrin/c-Abl Interaktion reguliert DNA Reparatur und Strahlensensibilität humaner Tumorzellen
Koppenhagen, P.; Dickreuter, E.; Cordes, N.
  • Abstract in refereed journal
    Strahlentherapie und Onkologie 192(2016)Suppl.1, 39
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Registration No. 25145 - Permalink

Discoidin Domain Receptor 1 targeting impairs GBM cell invasion and mediates radiochemosensitization by induction of autophagy
Klapproth, E.; Vehlow, A.; Cordes, N.
  • Abstract in refereed journal
    European Journal of Cancer 61(2016)Suppl.1, S160-S161
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Registration No. 25144 - Permalink

DDR1 reguliert Radiochemosensitivität sowie Invasivität humaner Glioblastomzellen
Klapproth, E.; Vehlow, A.; Cordes, N.
  • Abstract in refereed journal
    Strahlentherapie und Onkologie 192(2016)Suppl.1, 42-43
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Registration No. 25143 - Permalink

A Bayesian network model for acute dysphagia prediction in NSCLC patients
Jochems, A. T. C.; Deist, T. M.; Troost, E. G. C.; Dekker, A.; Faivre-Finn, C.; Oberije-Dehing, C.; Lambin, P.
  • Abstract in refereed journal
    Radiotherapy and Oncology 119(2016)Suppl.1, S118-S119
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Registration No. 25142 - Permalink

Targeting of beta1 integrins compromises DNA damage repair for radiosensitization of head and neck cancer cells
Dickreuter, E.; Eke, I.; Krause, M.; Borgmann, K.; van Vugt, M.; Cordes, N.
  • Abstract in refereed journal
    European Journal of Cancer 61(2016)Suppl.1, S1
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Registration No. 25140 - Permalink

Integration of 7T MRI into image-guided radiotherapy of glioblastoma: a feasibility study
Compter, I.; Peerlings, J.; Eekers, D. B. P.; Postma, A. A.; Ivanov, D.; Wiggins, C.; Kubben, P.; Küsters, B.; Wesseling, P.; Ackermans, L.; Schijns, O. E. M. G.; Lambin, P.; Hoffmann, A. L.
  • Abstract in refereed journal
    Radiotherapy and Oncology 119(2016)Suppl.1, S867-S868
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Registration No. 25139 - Permalink

Re-Mining – Gewinnung strategischer Metalle und anderer Mineralien aus sächsischen Bergbauhalden
Büttner, P.; Gutzmer, J.
Abstract: 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.
Keywords: Re-Mining, Halden, Tailings, Ressourcentechnologie, Resource, Rohstoffe, 3D-Model, GOCAD, Exploration, Processing, Aufbereitung, Erzgebirge, Tiefenbachhalde, Spülhalde, Davidschacht
  • Book chapter
    in: Mineralische Nebenprodukte und Abfälle, Band 3, Berlin: TK Verlag Karl J. Thomé-Kozmiensky, 2017, 978-3-944310-28-2, 383-393
  • Invited lecture (Conferences)
    Berliner Konferenz mineralische Nebenprodukte und Abfälle, 20.-21.06.2017, Berlin, Germany
  • Invited lecture (Conferences)
    1st Workshop Goiano de Terras Raras, 23.-25.05.2017, Catalao, Brasil
  • Invited lecture (Conferences)
    EIT Raw Materials Brookerage Event "ReMining and process residues", 18.-19.01.2017, Berlin, Germany
  • Invited lecture (Conferences)
    Economic Governance und Ordonomik: Die Nutzung von Ressourcen - mehr als eine ökonomische Fragestellung, 17.-19.02.2017, Halle, Germany
Registration No. 25138 - Permalink

SMSB - Gewinnung strategischer Metalle und Mineralien aus sächsischen Bergbauhalden
Büttner, P.; Osbahr, I.; Luhmer, R.; Pilz, C.; Uhlig, S.; Leißner, T.; Pätzold, C.; Scheel, M.; Jahns, C.; Martin, M.; Gutzmer, J.
Abstract: 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.
Keywords: Re-Mining, SMSB, Resource, Freiberg, Tailings, Processing, GOCAD, 3D-Model, INTRA r³+, Resource Technology, Halden, Tiefenbachhalde, Spülhalde, Davidschacht, Aufbereitung, Exploration
  • Book chapter
    in: Innovative Technologien für Ressourceneffizienz - Strategische Metalle und Mineralien, Stuttgart: Fraunhofer Verlag, 2017, 978-8396-1102-9, 345-360
Registration No. 25137 - Permalink

Biomarker für die individualisierte Strahlentherapie
Linge, A.; Lohaus, F.; Löck, S.; Krause, M.; Baumann, M.
  • Book chapter
    Karl-Jürgen Wolf, Wolfram Knapp, Thomas Herrmann: Strahlenforschung in der Medizin – Relevanz und Perspektiven, Nova Acta Leopoldina - Neue Folge Band 121 Nummer 406, Stuttgart: Wissenschaftliche Verlagsgesellschaft, 2016, 333-344
Registration No. 25136 - Permalink

The Role of Cancer Stem Cells in Tumour Radioresponse
Linge, A.; Dubrovska, A.; Baumann, M.; Krause, M.
  • Book chapter
    Anscher, M.S., Valerie, K.: Strategies to Enhance the Therapeutic Ratio of Radiation as a Cancer Treatment, Switzerland: Springer International Publishing, 2016, 43-74
Registration No. 25135 - Permalink

FMISO as a Biomarker for Clinical Radiation Oncology
Zschaeck, S.; Steinbach, J.; Troost, E. G. C.
  • Book chapter
    Baumann, M.; Krause, M.; Cordes, N.: Molecular Radio-Oncology, Volume 198 of the series Recent results in Cancer Research,, Berlin Heidelberg: Springer Verlag, 2016, 189-201

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Registration No. 25134 - Permalink

Ambidextrous Idea Generation-Antecedents and Outcomes
Gurtner, S.; Reinhardt, R.
Abstract: 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. Registration No. 25133 - Permalink

Targeted next-generation sequencing of locally advanced squamous cell carcinomas of the head and neck reveals druggable targets for improving adjuvant chemoradiation
Tinhofer, I.; Budach, V.; Saki, M.; Konschak, R.; Niehr, F.; Jöhrens, K.; Weichert, W.; Linge, A.; Lohaus, F.; Krause, M.; Neumann, K.; Endris, V.; Sak, A.; Stuschke, M.; Balermpas, P.; Rödel, C.; Avlar, M.; Grosu, A. L.; Abdollahi, A.; Debus, J.; Belka, C.; Pigorsch, S.; Combs, S. E.; Mönnich, D.; Zips, D.; Baumann, M.; DKTK-ROG
Abstract: 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.

Keywords: Head and neck cancer; Human papilloma virus; Mutation profiles; Adjuvant chemoradiation; Cisplatin Registration No. 25131 - Permalink

A Compton camera prototype for prompt gamma medical imaging
Thirolf, P. G.; Aldawood, S.; Böhmer, M.; Bortfeldt, J.; Castelhano, I.; Dedes, G.; Fiedler, F.; Gernhäuser, R.; Golnik, C.; Helmbrecht, S.; Hueso-González, F.; von D. Kolff, H.; Kormoll, T.; Lang, C.; Liprandi, S.; Lutter, R.; Marinšek, T.; Maier, L.; Pausch, G.; Petzoldt, J.; Römer, K.; Schaart, D.; Parodi, K.
Abstract: 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.

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Registration No. 25130 - Permalink

The impact of CDK9 on radiosensitivity, DNA damage repair and cell cycling of HNSCC cancer cells
Storch, K.; Cordes, N.
Abstract: 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. Registration No. 25129 - Permalink

ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer, version 1.1.
Offersen, B. V.; Boersma, L. J.; Kirkove, C.; Hol, S.; Aznar, M. C.; Sola, A. B.; Kirova, Y. M.; Pignol, J.-P.; Remouchamps, V.; Verhoeven, K.; Weltens, C.; Arenas, M.; Gabrys, D.; Kopek, N.; Krause, M.; Lundstedt, D.; Marinko, T.; Montero, A.; Yarnold, J.; Poortmans, P. Registration No. 25128 - Permalink

Independent validation of the prognostic value of cancer stem cell marker expression and hypoxia-induced gene expression for patients with locally advanced HNSCC after postoperative radiotherapy
Linge, A.; Löck, S.; Krenn, C.; Appold, S.; Lohaus, F.; Nowak, A.; Gudziol, V.; Baretton, G. B.; Buchholz, F.; Baumann, M.; Krause, M.
Abstract: 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.

Keywords: Biomarker; Cancer stem cells; HNSCC; HPV; Hypoxia; Postoperative radiochemotherapy; Validation

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Registration No. 25127 - Permalink

Clinical trials for personalized glioblastoma radiotherapy: Markers for efficacy and late toxicity but often delayed treatment – Does that matter?
Lattermann, A.; Baumann, M.; Krause, M. Registration No. 25126 - Permalink

Targeting of β1 integrins impairs DNA repair for radiosensitization of head and neck cancer cells
Dickreuter, E.; Eke, I.; Krause, M.; Borgmann, K.; van Vugt, M. A.; Cordes, N.
Abstract: 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. Registration No. 25125 - Permalink

Bridging the valley of death: The new Radiotherapy & Oncology section “First in man - Translational innovations in radiation oncology.”
Baumann, M.; Overgaard, J. Registration No. 25124 - Permalink

Shining light on the beauty of f-electron systems: principles and perspectives of X-ray spectroscopy
Kvashnina, K. O.
Abstract: 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
  • Other
    Univerisite Grenoble Alpes (UGA), 2017
    Mentor: Andreas Scheinost
Registration No. 25120 - Permalink

Polyphenols delivery by polymeric materials: challenges in cancer treatment.
Vittorio, O.; Curcio, M.; Cojoc, M; Goya, G.; Hampel, S.; Iemma, F.; Dubrovska, A; Cirillo, G.
Abstract: 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.
Keywords: Nanocarrier, polyphenols, cancer therapy, polymeric materials Registration No. 25117 - Permalink

CD98hc a potential biomarker for therapy outcome and a putative therapeutical target for radiosensitization of head and neck squamous cell carcinoma
Digomann, D.; Kurth, I.; Linge, A.; Hein, L.; Heiden, S.; Baumann, M.; Dubrovska, A.
Abstract: 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

Keywords: CD98, HNSCC, Radioresistance
  • Abstract in refereed journal
    Strahlentherapie und Onkologie 192(2016)Suppl.1, 124
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Registration No. 25114 - Permalink

X-ray Structures of Succinimidyl Halobenzoates
Mamat, C.; Weiss, D.-H.; Köckerling, M.
Corresponding author: Mamat, Constantin
Corresponding author: Köckerling, Martin
Abstract: The crystal and molecular structures of five succinimidyl halobenzoates are reported. Corresponding derivatives with the respective halo-radionuclide (18F, 76Br, 123I/124I/125I/131I) were prepared and used for the radiolabeling of biologically active (macro-)molecules (peptides, proteins, antibodies) under mild labeling conditions. All compounds crystalized from petroleum ether/ethyl acetate mixtures.
Keywords: building block; radiolabeling; [18F]SFB; SIB; SBrB Registration No. 25104 - Permalink

Charge Collection Efficiency in a segmented semiconductor detector interstrip region
Alarcon-Diez, V.; Vickridge, I.; Jakšić, M.; Grilj, V.; Schmidt, B.; Lange, H.
Abstract: Charged particle semiconductor detectors have been used in Ion Beam Analysis (IBA) for over four decades without great changes in either design or fabrication. However one area where improvement is desirable would be to increase the detector solid angle so as to improve spectrum statistics for a given incident beam fluence. This would allow the use of very low fluences opening the way, for example, to increase the time resolution in real-time RBS or for analysis of materials that are highly sensitive to beam damage. In order to achieve this goal without incurring the costs of degraded resolution due to kinematic broadening or large detector capacitance, a single-chip segmented detector (SEGDET) was designed and built within the SPIRIT EU infrastructure project. In this work we present the Charge Collection Efficiency (CCE) in the vicinity between two adjacent segments focusing on the interstrip zone. Microbeam Ion Beam Induced Charge (IBIC) measurements with different ion masses and energies were used to perform X-Y mapping of (CCE), as a function of detector operating conditions (bias voltage changes, detector housing possibilities and guard ring configuration). We show the (CCE) in the edge region of the active area and have also mapped the charge from the interstrip region, shared between adjacent segments. The results indicate that the electrical extent of the interstrip region is very close to the physical extent of the interstrip and guard ring structure with interstrip impacts contributing very little to the complete spectrum. The interstrip contributions to the spectra that do occur, can be substantially reduced by an offline anti-coincidence criterion applied to list mode data, which should also be easy to implement directly in the data acquisition software.
Keywords: Segmented detector; IBIC; Charge Collection Efficiency; Interstrip

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Registration No. 25103 - Permalink

Nanoparticles for radiooncology: Mission, vision, challenges
Kunz-Schughart, L. A.; Dubrovska, A.; Peitzsch, C.; Ewe, A.; Aigner, A.; Schellenburg, S.; Muders, M. H.; Hampel, S.; Cirillo, G.; Iemma, F.; Tietze, R.; Alexiou, C.; Stephan, H.ORC; Zarschler, K.; Vittorio, O.; Kavallaris, M.; Parak, W. J.; Mädler, L.; Pokhrel, S.
Abstract: 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.

Keywords: Nanoparticles, Radiosensitizers, Radiotherapy, Radiooncology, Magnetic Particles, Flame Spray Pyrolysis
  • Biomaterials 120(2017), 155-184
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Registration No. 25101 - Permalink

Self-Organized Semiconductor Patterning by Polyatomic Broad Beam Ion Irradiation
Pilz, W.; Bischoff, L.; Böttger, R.; Laufer, P.; Tajmar, M.
Abstract: Surface patterning based on self-organized nano-structures on i.e. semiconductor materials formed by heavy mono - and polyatomic ion irradiation from Liquid Metal (Alloy) Ion Sources (LMAIS) is a very promising technique. To overcome the lack of only very small treated areas by applying a Focused Ion Beam (FIB) instrument this technology was transferred into larger single-end ion beam systems like an ion implanter. Main component is an ion beam injector based on high current LMAIS, developed for space propulsion systems combined with suited ion optics allocating ion currents in the µA range in a nearly parallel beam of a few mm in diameter. The mass selection of the needed ion species can be performed either by an introduced ExB mass separator (Wien filter) and/or the existing magnet of the ion implanter itself which also can define the final ion energy up to 200 keV.
Different types of LMAIS (needle, porous emitter, capillary) are presented and characterized. The ion beam injector design is specified as well as the implementation of this module into a high current ion implanter (Danfysik Series 1090) operating at the HZDR Ion Beam Center (IBC). Finally the obtained results of large area surface modification of Ge using Bi2+ polyatomic ions from a GaBi capillary LMAIS at room temperature will be presented and discussed.

Keywords: Self-Organized Patterning; Polyatomic Ions; Broad Beam Ion Irradiation
  • Lecture (Conference)
    Nationales Treffen der deutschen Ionenstrahl-PhysikerInnen und -MaterialwissenschaftlerInnen, 12.-15.02.2017, Göttingen, Germany
Registration No. 25099 - Permalink

Defect-induced magnetism in SiC probed by nuclear magnetic resonance
Zhang, Z. T.; Dmytriieva, D.; Molatta, S.; Wosnitza, J.; Wang, Y.; Helm, M.; Zhou, S.; Kühne, H.
Abstract: We give evidence for intrinsic defect-induced bulk paramagnetism in SiC by means of 13C and 29Si nuclear magnetic resonance (NMR) spectroscopy. The temperature dependence of the internal dipole-field distribution, probed by the spin part of the NMR Knight shift and the spectral linewidth, follows the Curie law and scales very well with the macroscopic dc susceptibility. In order to quantitatively analyze the NMR spectra, a microscopic model based on dipole-dipole interactions was developed. The very good agreement between these simulations and the NMR data establishes a direct relation between the frequency distribution of the spectral intensity and the corresponding real-space volumes of nuclear spins. The presented approach by NMR can be applied to a variety of similar materials and, thus, opens a new avenue for the microscopic exploration and exploitation of diluted bulk magnetism in semiconductors. Registration No. 25098 - Permalink

Backward-forward reaction asymmetry of neutron elastic scattering on deuterium
Pirovano, E.; Beyer, R.; Junghans, A. R.; Nankov, N.; Nolte, R.; Nyman, M.; Plompen, A. J. M.
Abstract: A new measurement of the angular distribution of neutron elastic scattering on deuterium was carried out at the neutron time-of-flight facility nELBE. The backward-forward asymmetry of the reaction was investigated via the direct detection of neutrons scattered at the laboratory angle of 15◦ and 165◦ from a polyethylene sample enriched with deuterium. In order to extend the measurement to neutron energies below 1 MeV, 6Li glass scintillators were employed. The data were corrected for the background and the multiple scattering in the target, the events due to scattering on deuterium were separated from those due to carbon, and the ratio of the differential cross section at 15◦ and 165◦ was determined. The results, covering the energy range from 200 keV to 2 MeV, were found to be in agreement with the theoretical predictions calculated by Canton et al. [Eur. Phys. J. A 14, 225 (2002)] and by Golak et al. [Eur. Phys. J. A 50, 177 (2014)]. The comparison with the evaluated nuclear data libraries indicated CENDL-3.1, JEFF-3.2, and JENDL-4.0 as the evaluations that best describe the asymmetry of n-d scattering.
ENDF/B-VII.1 is compatible with the data for energies below 700 keV, but above the backward to forward ratio is higher than measured. ROSFOND-2010 and BROND-2.2 resulted to have little compatibility with the data.

Keywords: nELBE, neutron, time-of-flight, elastic scattering, deuterium

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Registration No. 25095 - Permalink

Elastic Moduli in Cadmium Selenide Doped with Chromium
Averkiev, N. S.; Bersuker, I. B.; Gudkov, V. V.; Zhevstovskikh, I. V.; Sarychev, M. N.; Zherlitsyn, S.; Yasin, S.; Korostelin, Y. V.
Abstract: Temperature dependence of elastic moduli (C11 − C12 ) / 2 , C33 , and C44, the latter for the piezo-active and non-piezo-active versions, have been measured in the interval of 4 - 180 K at 28 - 262 MHz in a CdSe: Cr2+ crystal. Anomalies below 40 K have been found for all the moduli, except C33 . The interpretation of the results has been carried out involving the Jahn-Teller effect and relaxation between the equivalent distortions of the tetrahedral CrSe4 centers. Registration No. 25092 - Permalink

Energy dependence of the electron-boson coupling strength in the electron-doped cuprate superconductor Pr1.85Ce0.15CuO4−δ
Beck, M.; Klammer, M.; Rousseau, I.; Obergfell, M.; Leiderer, P.; Helm, M.; Kabanov, V. V.; Diamant, I.; Rabinowicz, A.; Dagan, Y.; Demsar, J.
Abstract: The quest for a pairing boson in cuprate high-temperature superconductors is one of the outstanding Tasks of solid-state physics. Numerous time-resolved studies of pair breaking, related to pairing by time-reversal symmetry, have been performed using femtosecond optical pulses. By considering energy Relaxation pathways between charge, spin, and lattice degrees of freedom, evidence for both phonon and antiferromagnetic fluctuationmediated pairing has been obtained. Here we present a study of the superconducting-state depletion process in an electron-doped cuprate Pr1.85Ce0.15CuO4−δ , where the superconducting gap is smaller than the energy of relevant bosonic excitations. When pumping with above-gap terahertz pulses, we find that the absorbed energy density required to deplete superconductivity, Adep, matches the thermodynamic condensation energy. On the contrary, by near-infrared pumping, Adep is an order of Magnitude higher, as in the case of hole-doped, large-gap cuprates. These results imply that only a small subset of bosons, which are generated during the relaxation of optically excited carriers, contributes to pairing. This observation implies that, contrary to the common assumptions, electron-boson coupling in cuprates is strongly energy dependent.
Keywords: superconductor, terahertz, free electron laser Registration No. 25089 - Permalink

Field-induced gapless electron pocket in the superconducting vortex phase of YNi2B2C as probed by magnetoacoustic quantum oscillations
Nössler, J.; Seerig, R.; Yasin, S.; Uhlarz, M.; Zherlitsyn, S.; Behr, G.; Drechsler, S.-L.; Fuchs, G.; Rosner, H.; Wosnitza, J.
Abstract: By use of ultrasound studies we resolved magnetoacoustic quantum oscillation deep into the mixed state of the multiband nonmagnetic superconductor YNi2B2C. Below the upper critical field, only a very weak additional damping appears that can be well explained by the field inhomogeneity caused by the flux-line lattice in the mixed state. This is clear evidence for no or a vanishingly small gap for one of the bands, namely, the spheroidal α band. This contrasts de Haas–van Alphen data obtained by use of torque magnetometry for the same sample, with a rapidly vanishing oscillation signal in the mixed state. This points to a strongly distorted flux-line lattice in the latter case that, in general, can hamper a reliable extraction of gap parameters by use of such techniques. Registration No. 25088 - Permalink

Interaction of uranium (VI) with cellulose degradation products
Brinkmann, H.; Moll, H.
Abstract: Cellulosic material is present in low and intermediate level wastes in considerable amounts. In the case of ground water ingressing into cementitious backfill material a hyperalkaline environment will be established. Since cellulose will be relatively fast degraded under alkaline conditions, there is a high risk that small organic, water soluble molecules will be formed. These molecules can act as complexing agents for radionuclides and thereby affecting their sorption behavior and solubility adversely. Therefore the focus of current investigations is on the interaction of uranium (VI) with Isosaccharinic acid as main degradation product as well as with acetate. The progress and results of these investigations as part of the MIND project (work package 1) will be presented.
Keywords: Cellulose, Isosaccharinic acid, Acetate, Uranium
  • Lecture (others)
    TD-315 Joint BN, GD, HT, MA Meeting 2017, 06.-07.02.2017, St. Ursanne, Schweiz
Registration No. 25085 - Permalink

Status of the development of compact laser-driven ion beam therapy
Pawelke, J.
Abstract: For a decade we have been developing laser-based particle acceleration for more compact and cost effective ion therapy facilities. The current status will be presented, discussing not only high power laser systems and laser targets to generate therapeutically applicable beams but also technical solutions for dosimetry, beam transport and dose delivery along with the radiobiological consequences of the short ultra-intense pulses of laser-driven beams.
  • Invited lecture (Conferences)
    32nd Conference on Clinical and Experimental Research in Radiation Oncology, 14.-21.01.2017, Les Menuires, France
Registration No. 25082 - Permalink

Ab initio study of interaction of helium with edge and screw dislocations in tungsten
Bakaev, A.; Terentyev, D.; Grigorev, P.; Zhurkin, E. E.
Abstract: The interaction of a single He atom with edge and screw dislocations in tungsten has been studied using ab initio calculations. It was revealed that He is strongly attracted to the core of both dislocations with the interaction energy of -1.3 and -3.0 eV for screw and edge dislocations, respectively, which corresponds to the detrapping temperature in thermal desorption spectroscopy experiments of about 500 K and 1050 K, respectively. The lowest energy positions for He around the dislocation cores are identified and the atomic structures are rationalized on the basis of elasticity theory considerations. Both types of dislocations exhibit a higher binding energy for He as compared to the He-He binding (known as self-trapping) and are weaker traps as compared to a single vacancy. It is, thus, concluded that the strong attraction to dislocation lines can contribute to the nucleation of He clusters in the temperature range which already excludes He self-trapping.
Keywords: Dislocations Helium Tungsten Ab initio
  • Nuclear Instruments and Methods in Physics Research B 393(2017), 150-154
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Registration No. 25081 - Permalink

A fluorescence anisotropy‐based assay to determine the activity of tissue transglutaminase in human cancer cell lines
Ullm, S.; Wodtke, R.; Pietzsch, J.; Löser, R.
Abstract: High activity of tissue transglutaminase (TGase 2) in various tumors is associated with both their increased metastatic and invasive potential and their resistance towards chemotherapy and radiation. This renders TGase 2 an attractive target for the development of agents that are capable of targeting the tumor-associated TGase 2 for both imaging and therapeutic approaches [1].
To identify Inhibitor-based compounds for these purposes, the establishment of activity assays that allow their characterization both in vitro and at the cellular level is essential. We previously reported a kinetic fluorescence anisotropy (FA)-based assay to determine the transamidase activity of guinea pig TGase 2 [2] which follows the incorporation of fluorescently labeled (either fluoresceine or rhodamine B) cadaverine derivatives into N,N-dimethylated casein (DMC) over time. Using this assay, we were able to show that the method of FA ensures the absence of background signal and a high reproducibility in a homogenous assay design.
Here we apply the FA assay using DMC and a newly developed rhodamine B-cadaverine conjugate to recombinant human TGase 2 for the kinetic characterization of selected inhibitors and the active-site titration of the enzyme. Due to the favorable signal-to-noise ratio, it was furthermore possible to apply the FA assay for determining cellular TGase 2 in 25 human cell models by measuring the enzyme activity in the whole cell lysate and calculating the respective protein amount. The obtained results were compared with those of a densitometric Western Blot analysis, showing a clear correlation between the two data sets. The human lung cancer cell line NCI-H292 and the human breast cancer cell line MDA-MB-231 were found to exhibit the highest amount of activatable TGase 2 among the tested cancer cell lines, whereas the human cerebral endothelial cell line hCMEC-D3 showed the highest activity among the tested non-cancerous cell lines. To prove that the observed FA signal is caused by TGase 2 activity, N2-phenylacetyl-N6-acryloyl-lysine-4-(6-methylpyridine-2-yl)piperazide [3], which has previously been characterized as irreversible inactivator of this enzyme, was utilized. Application of this inhibitor resulted in a substantial reduction of the FA signal.

References:
[1] Pietsch et al. Bioorg. Med. Chem. Lett. 2013, 23, 6528.
[2] Hauser et al. Amino Acids 2016 DOI: 10.1007/s00726-00016-02192-00725.
[3] Wityak et al. ACS Med. Chem. Lett. 2012, 3, 1024.
  • Poster
    Transglutaminases in Human Disease Processes, 10.-15.07.2016, Girona, Spanien
Registration No. 25077 - Permalink

Expression and Activity of Tissue Transglutaminase in the Response to Gelatin-based Hydrogels in vitro and in vivo
Ullm, S.; Wodtke, R.; Tondera, C.; Löser, R.; Pietzsch, J.
Abstract: Tissue transglutaminase (TGase 2) is proposed to be important for biomaterial-cell or -tissue interactions due to its presence and versatile functions in the extracellular environment. For example, TGase 2 catalyzes the crosslinking of proteins of the extracellular matrix through its Ca2+-dependent transamidase activity or enhances the interactions between fibronectin, integrins, and syndecan-4 via its role as scaffold protein. Through these functions, TGase 2 mediates the adhesion, migration and motility of cells. Additionally, TGase 2 is a key player during the development of fibrosis. Consequently, TGase 2 might be a potential target for the improvement and visualization of tissue regeneration following biomaterial implantation. Here, we studied the expression pattern and activity of TGase 2 in the response to gelatin-based hydrogels with tailorable elastic properties and degradation behavior due to different degrees of crosslinking.
Solutions of 10 wt.-% gelatin were crosslinked with 3- (G10_LNCO3) or 8-fold (G10_LNCO8) excess of isocyanate groups of lysine diisocyanate ethyl ester compared to amino groups of gelatin. Primary human aortic endothelial cells (HAEC) and human leukemia THP-1 and HL-60 cells, differentiated to macrophages (Mɸ) or granulocytes (Gɸ), were seeded either directly on the hydrogel films or cultivated with material eluates in order to simulate hydrolytic or enzymatic hydrogel degradation in vivo. Expression levels of intracellular and secreted TGase 2 were analyzed via Western blotting [1]. Additionally, hydrogels were implanted subcutaneously in immunocompetent, hairless SKH-1 mice. TGase 2 expression at the implantation site was detected ex vivo by immunohistochemistry at several time points up to 112 days after implantation. The presence of activatable TGase 2 in tissue sections was confirmed in vitro by incorporation of fluorescently labelled cadaverine derivatives [2] at sites of TGase 2 expression. To prove that the incorporation is caused by TGase 2, the staining was performed in the presence and absence of a recently described irreversible inhibitor for TGase 2 [3].
HAEC showed high expression and secretion of TGase 2, independent from hydrogel contact. THP-1 Mɸ highly expressed TGase 2, and increased its secretion after direct hydrogel contact. In contrast, HL-60 Mɸ and Gɸ exhibited enhanced expression of TGase 2 after direct contact to the hydrogels, without secreting TGase 2. These results demonstrate that TGase 2 expression and secretion by Mɸ and Gɸ are influenced by contact to the hydrogel surface structure and not by hydrogel degradation products. Additionally, the hydrogels with higher content of diurealysine junction units (G10_LNCO8) induced higher effects than G10_LNCO3. Ex vivo analysis of tissue sections by immunohistochemistry revealed enhanced expression levels of activatable TGase 2 around the hydrogels 14 and 21 days after implantation, indicating a role of TGase 2 in hydrogel integration and tissue remodelling.
Our results revealed that contact to the gelatin-based hydrogels influenced TGase 2 expression and secretion by Mɸ and Gɸ in vitro, as well as expression of activatable TGase 2 in vivo. This underlines TGase 2 to be a promising theranostic target during processes of biomaterial integration.
References:
[1] Ullm et al. Biomaterials 2014, 35, 9755-9766
[2] Hauser et al. Amino Acids 2016, DOI 10.1007/s00726-00016-02192-00725
[3] Wityak et al. ACS Med. Chem. Lett. 2012, 3, 1024-1028
  • Poster
    Transglutaminases in Human Disease Processes, 10.-15.07.2016, Girona, Spanien
Registration No. 25076 - Permalink

N6-Acryloyl-lysine piperazides as irreversible inhibitors of transglutaminase 2 ― synthesis and structure activity relationships
Wodtke, R.; Jäckel, E.; Wong, A.; Lohse, M.; Bauer, D.; Ullm, S.; Steinbach, J.; Pietzsch, J.; Löser, R.
Abstract: Various kinds of tumour entities are characterised by an increased activity of transglutaminase 2 (TGase 2), which contributes to an enhanced invasive potential of the tumour cells and their resistance to chemo- and radiotherapy. Therefore, this enzyme represents an interesting target for the development of PET tracers for functional imaging of tumours in vivo [1].
Among the TGase 2 inhibitors described in the literature, N6-acryloyl-lysine-4-arylpiperazides reported by Wityak et al. [2] seem to be most suitable for radiotracer development as these compounds exhibit both strong inhibitory potential and selectivity towards human TGase 2 and show favourable pharmacokinetic properties. Based on this class of compounds, derivatives that allow for labelling with radionuclides such as fluorine-18 and iodine-124 were prepared and their inhibitory potential towards TGase 2 was evaluated.
The N2-acyl-N6-acryloyl-lysine-4-pyridylpiperazides were synthesised in a sequence consisting of N6-acrylation, PyBOP-mediated amide bond formation, Boc deprotection and N2-acylation starting from N2-Boc-lysine. The required pyridylpiperazines were obtained commercially or prepared in a few steps. All final compounds were evaluated in two independent kinetic assays, which detect either the transamidase [3] or hydrolase activity [4] of TGase 2, respectively, with N2-phenylacetyl-N6-acryloyl-lysine-4-(6-methylpyridine-2-yl)piperazide [2] serving as benchmark inhibitor.
Using the outlined synthetic route a series of more than 50 N2-acyl-N6-acryloyl-lysine-4-pyridylpiperazides was prepared in good yields. The kinetic characterisation of the compounds revealed some interesting structure-activity relationships. For example, replacing the 6-methylpyridine-2-yl moiety of the benchmark inhibitor by a 2-nitro-5-pyridyl moiety led to a significantly increased inhibitory effect towards human TGase 2. Furthermore, substitution of the methyl group by hydrogen or a halogen atom (F, Cl, Br and I) revealed a direct correlation between the van der Waals radius of the substituent and the inhibitory effect towards human TGase 2, with the inhibitor containing iodine being even more potent than the benchmark inhibitor. Covalent docking studies provided information about the binding mode of this inhibitor class for the first time and, thus, allowed for explaining the trends observed in the activity assays and give hints for further improvement of inhibitory potency by specific structural variations.
In addition to their interaction with TGase 2, the inhibitors are characterised for their pharmacokinetic properties by the determination of appropriate parameters in vitro.
References:
[1] Pietsch et al. Bioorg. Med. Chem. Lett. 2013, 23, 6528. [2] Wityak et al. ACS Med. Chem. Lett. 2012, 3, 1024. [3] Hauser et al. Amino Acids 2016 DOI 10.1007/s00726-00016-02192-00725. [4] Wodtke et al. ChemBioChem 2016 DOI 10.1002/cbic.201600048
  • Poster
    Transglutaminases in Human Disease Processes, 10.-15.07.2016, Girona, Spanien
Registration No. 25075 - Permalink

Comparative analysis of radiolabeled monoclonal antibodies and antibody fragments for immunotherapy of Prostate Stem Cell Antigen expressing tumors
Oertel, F.; Arndt, C.; Feldmann, A.; Bachmann, M.; Bergmann, R.; Steinbach, J.; Pietzsch, H.-J.
Abstract: Aim: Advances in antibody engineering have led to the development of a multiplicity of antibody types for radioimmunotherapy. Predominantly, this development was concentrated on generating variations in the antibody size, which evidently influences the pharmacokinetics and tumor uptake. However, it is still discussed, which size has most suitable properties for radioimmunotherapy approaches. Here, two different antibody types, monoclonal antibodies (mAbs, 150 kDa) and thereof derived single-chain variable fragments (scFv, 35 kDa), were compared, that are directed against the prostate stem cell antigen (PSCA). Due to its overexpression on the surface of various cancers, including prostate, pancreas and bladder cancer, PSCA is proposed to be a promising tumor target structure for antibody-based immunotherapy.

Methods: In this study, two different anti-PSCA mAb clones, RD1 and RD2, as well as their respective anti-PSCA scFvs were compared with regard to their binding properties towards PSCA, using flow cytometry analysis. Above, the anti-PSCA mAbs were conjugated with the radionuclide chelating agent CHX-A’'-DTPA and subsequently radiolabeled with 177Lu. The radiolabeled mAb-conjugates were, then, characterized regarding binding properties on PC3-PSCA cells in vitro.

Results: As determined by flow cytometry, non-radiolabeled anti-PSCA mAbs RD1 and RD2 show a high affinity, with a dissociation constant of 10 and 6 nM, respectively. Even though, the scFvs of RD1 and RD2 exhibit a lower affinity in comparison to their mAbs counterpart, they maintain a moderate Kd-value (170 and 98 nM) that is sufficient to proceed with conjugation and radiolabeling analogous to the mAbs. Conjugation of three CHX-A’’-DTPA-chelators to the mAbs had no influence on binding affinity towards the PSCA. Subsequent radiolabeling of the mAb-conjugates could be performed with high radiochemical purity (> 95%). Similar to the non-radiolabeled mAbs, the binding affinity of 177Lu-labeled (CHX-A’’-DTPA)3-RD1 or RD2 was high with 12 and 19 nM, respectively. Summing up, both anti-PSCA mAb were successfully radiolabeled with 177Lu without losing their binding properties to PSCA. Thus, these molecules are attractive candidates for radioimmunotherapy of PSCA-positive cancers.
  • Lecture (Conference)
    24. Jahrestagung der Arbeitsgemeinschaft Radiochemie/Radiopharmazie 2016, 29.09.-01.10.2016, Morschach, Schweiz
Registration No. 25074 - Permalink

Toward high-energy laser-driven ion beams: Nanostructured double-layer targets
Passoni, M.; Sgattoni, A.; Prencipe, I.; Fedeli, L.; Dellasega, D.; Cialfi, L.; Choi, I. W.; Kim, I. J.; Janulewicz, K.  A.; Lee, H. W.; Sung, J. H.; Lee, S. K.; Nam, C. H.
Abstract: The development of novel target concepts is crucial to make laser-driven acceleration of ion beams suitable for applications. We tested double-layer targets formed of an ultralow density nanostructured carbon layer (∼7  mg/cm3, 8–12  μm–thick) deposited on a μm–thick solid Al foil. A systematic increase in the total number of the accelerated ions (protons and C6+) as well as enhancement of both their maximum and average energies was observed with respect to bare solid foil targets. Maximum proton energies up to 30 MeV were recorded. Dedicated three-dimensional particle-in-cell simulations were in remarkable agreement with the experimental results, giving clear indication of the role played by the target nanostructures in the interaction process.

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Registration No. 25073 - Permalink

Towards atomic physics in particle in cell on GPUs (PIConGPU), photon scattering and nanometer and femtosecond probing of hot dense matter with SAXS
Kluge, T.
Abstract: Ultrafast heating of solids or solid density plasmas can provide a unique, transient and non-thermal state of matter that enables the study e.g. of ultrafast ionization and excitation, recombination, photon and electron transport. Heating can be achieved directly and indirectly by irradiation with ultra-intense optical lasers or volumetrically with XFELs. Yet, the state-of-the-art theoretical description needed to simulate those processes in particle in cell (PIC) simulations is based on average and effective simplistic assumptions, and hence not reliable for ultrashort, non-thermal states. We present our approach and status of implementing explicit atomic physics in PIConGPU, and introduce the first spin-off tool ParaTAXIS that simulates explicitly photon scattering using PIC methods. This enables implementation of arbitrary scattering physics, multiple scattering, full treatment of X-ray beam properties and fast plasma dynamics. We also demonstrate a novel experimental method based on Small Angle X-ray Scattering to probe such physics on a few nanometer and few femtosecond level simultaneously in ultra-intensity optical laser heated solids.
  • Poster
    Radiative Properties of Hot Dense Matter Workshop, 05.-09.12.2016, Santa Barbara, USA (CA)
Registration No. 25069 - Permalink

Nanometer-scale characterization of laser-driven plasmas, compression, shocks and phase transitions, by coherent small angle x-ray scattering
Kluge, T.; Rödel, M.; Pelka, A.; Mcbride, E. E.; Bussmann, M.; Fletcher, L.; Galtier, E.; Laso Garcia, A.; Gutt, C.; Lee, H. J.; Nagler, B.; Rödel, C.; Glenzer, S.; Schramm, U.; Cowan, T. E.
Abstract: Combining ultra-intense short-pulse and high-energy long-pulse lasers, with hard X-ray FELs, such as the Helmholtz International Beamline for Extreme Fields (HIBEF) [1] at European XFEL [2], or MEC at LCLS [3], holds the promise to revolutionize our understanding of many High Energy Density Physics phenomena. Examples include the relativistic electron generation, transport, and bulk plasma response [4], and ionization dynamics and heating [5] in relativistic laser-matter interactions, or the dynamics of laser-driven shocks, quasi-isentropic compression, and the kinetics of phase transitions at high pressure [3,6]. Particularly interesting is Small Angle X-ray Scattering [4] and resonant scattering [5]. Their feasibility in laser-driven matter will be discussed for ultra-intense short pulse drive lasers and nanosecond lasers, including first results from demonstration experiments at LCLS (SLAC). Very sharp density changes from laser-driven compression are observed, having a step width of <10 nm, comparing to a resolution of several hundred nm achieved previously [6] with phase contrast imaging.
[1] www.hibef.eu
[2] www.xfel.eu
[3] J. Synchrotron Rad. 22, 520 (2015)
[4] Phys. Plasmas 21, 033110 (2014)
[5] http://arxiv.org/abs/1508.03988
[6] Sci. Rep. 3, 1633 (2013)
  • Invited lecture (Conferences)
    43rd EPS Conference on Plasma Physics, 04.-08.07.2016, Leuven, Belgium
Registration No. 25068 - Permalink

Prospective Validation of a Prognostic Computed Tomography-Based Radiomic Signature in Stage IV Non-Small Cell Lung Cancer
de Jong, E.; van Elmpt, W.; Leijenaar, R. T. H.; Carvalho, S.; Troost, E. G. C.; Hendriks, L. E. L.; Dingemans, A. M. C.; Lambin, P.
Abstract: there ist no abstract Registration No. 25067 - Permalink

Toward Shared Decision: Validated Clinical Nomogram for Personalized Long-Term Survival Prediction After Radiosurgery for Brain Metastases
Zindler, J. D.; Jochems, A.; Beumer, R.; Troost, E. G.; Lagerwaard, F.; Eekers, D. B.; Compter, I.; van der Toorn, P. P.; Essers, M.; Oei, B.; Hurkmans, C.; Bruynzeel, A.; Bosmans, G.; Lambin, P.
Abstract: there ist no abstract Registration No. 25066 - Permalink

Toward Distributed Conduction of Large-Scale Studies in Radiation Therapy and Oncology: Open-Source System Integration Approach
Skripcak, T.; Just, U.; Simon, M.; Buttner, D.; Lühr, A.; Baumann, M.; Krause, M.
Abstract: The conduct of multicenter studies in the field of radiation therapy and oncology is one of the key prerequisites for stimulating translational research and accelerating the application of healthcare innovations into day to day patient treatment. To effectively run such studies, the participating research institutions need access to radiotherapy-specific information technology (IT), which enables collection of case report forms (eCRFs) linked with medical imaging and treatment planning data. Existing commercial systems that provide multimodal data collection features may fit for industry funded clinical trials but do not consider academia needs for long-lasting and affordable IT infrastructure. This paper presents an alternative way for development of a sustainable clinical research IT platform based on open-source systems. The platform design is driven by an integration of its core components, namely, electronic data capture system (EDC), medical image archive (PACS), and patient identity management system (PIDG). Three deployment scenarios are described that allow setting up the platform in a central, virtually hosted or decentralized environment. The first production implementation of this infrastructure was established as RadiationDosePlan-Image/Biomarker-Outcome-platform (RadPlanBio) in September 2013. It is maintained by the German Cancer Consortium (DKTK), Dresden and the German Cancer Research Center (DKFZ), Heidelberg. Until now, it manages 9 studies across 11 sites with 600 enrolled subjects. This paper shows how the integration of open-source systems can drive the development of sustainable clinical research IT environment supporting translational research projects in the field of radiation therapy and oncology. © 2015 IEEE.
Keywords: Digital imaging and communication in medicine (DICOM); electronic data capture (EDC); open source; radiotherapy studies; software integration Registration No. 25065 - Permalink

Personalized radiation oncology: Epidermal growth factor receptor and other receptor tyrosine kinase inhibitors
Higgins, G. S.; Krause, M.; Mckenna, W. G.; Baumann, M.
Abstract: Molecular biomarkers are currently evaluated in preclinical and clinical studies in order to establish predictors for treatment decisions in radiation oncology. The receptor tyrosine kinases (RTK) are described in the following text. Among them, the most data are available for the epidermal growth factor receptor (EGFR) that plays a major role for prognosis of patients after radiotherapy, but seems also to be involved in mechanisms of radioresistance, specifically in repopulation of tumour cells between radiotherapy fractions. Monoclonal antibodies against the EGFR improve locoregional tumour control and survival when applied during radiotherapy, however, the effects are heterogeneous and biomarkers for patient selection are warranted. Also other RTK’s such as c-Met and IGF-1R seem to play important roles in tumour radioresistance. Beside the potential to select patients for molecular targeting approaches combined with radiotherapy, studies are also needed to evluate radiotherapy adaptation approaches for selected patients, i.e. adaptation of radiation dose, or, more sophisticated, of target volumes. © Springer-Verlag Berlin Heidelberg 2016.
Keywords: Biomarker; EGFR; HER-2; Radiotherapy; Receptor tyrosine kinases
  • Book chapter
    Baumann, M.; Krause, M.; Cordes, N.: Molecular Radio-Oncology, Volume 198 of the series Recent results in Cancer Research, Berlin Heidelberg: Springer Verlag, 2016, 107-122
    DOI-Link: http://dx.doi.org/10.1007/978-3-662-49651-0_5
Registration No. 25063 - Permalink

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(-) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG.
Linge, A.; Löck, S.; Gudziol, V.; Nowak, A.; Lohaus, F.; von Neubeck, C.; Jütz, M.; Abdollahi, A.; Debus, J.; Tinhofer, I.; Budach, V.; Sak, A.; Stuschke, M.; Balermpas, P.; Rödel, C.; Avlar, M.; Grosu, A. L.; Bayer, C.; Belka, C.; Pigorsch, S.; Combs, S. E.; Welz, S.; Zips, D.; Buchholz, F.; Aust, D. E.; Baretton, G. B.; Thames, H. D.; Dubrovska, A.; Alsner, J.; Overgaard, J.; Baumann, M.; Krause, M.
Abstract: PURPOSE:

To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).
EXPERIMENTAL DESIGN:

Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control.
RESULTS:

Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P = 0.010) or the 26-gene signature (P = 0.002). In multivariate analyses, in patients with HPV16 DNA-negative but not with HPV16 DNA-positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P = 0.006; 26-gene signature: HR 10.27, P = 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P = 0.016; SLC3A2: HR 8.54, P = 0.037; CD44: HR 3.36, P = 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA-negative subgroup.
CONCLUSIONS:

We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA-negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies. Clin Cancer Res; 22(11); 2639-49. ©2016 AACR.
Registration No. 25060 - Permalink

Correlation of FMISO simulations with pimonidazole-stained tumor xenografts: A question of O2 consumption?
Wack, L. J.; Mönnich, D.; Yaromina, A.; Zips, D.; Baumann, M.; Thorwarth, D.
Abstract: PURPOSE:

To compare a dedicated simulation model for hypoxia PET against tumor microsections stained for different parameters of the tumor microenvironment. The model can readily be adapted to a variety of conditions, such as different human head and neck squamous cell carcinoma (HNSCC) xenograft tumors.
METHODS:

Nine different HNSCC tumor models were transplanted subcutaneously into nude mice. Tumors were excised and immunoflourescently labeled with pimonidazole, Hoechst 33342, and CD31, providing information on hypoxia, perfusion, and vessel distribution, respectively. Hoechst and CD31 images were used to generate maps of perfused blood vessels on which tissue oxygenation and the accumulation of the hypoxia tracer FMISO were mathematically simulated. The model includes a Michaelis-Menten relation to describe the oxygen consumption inside tissue. The maximum oxygen consumption rate M0 was chosen as the parameter for a tumor-specific optimization as it strongly influences tracer distribution. M0 was optimized on each tumor slice to reach optimum correlations between FMISO concentration 4 h postinjection and pimonidazole staining intensity.
RESULTS:

After optimization, high pixel-based correlations up to R(2) = 0.85 were found for individual tissue sections. Experimental pimonidazole images and FMISO simulations showed good visual agreement, confirming the validity of the approach. Median correlations per tumor model varied significantly (p < 0.05), with R(2) ranging from 0.20 to 0.54. The optimum maximum oxygen consumption rate M0 differed significantly (p < 0.05) between tumor models, ranging from 2.4 to 5.2 mm Hg/s.
CONCLUSIONS:

It is feasible to simulate FMISO distributions that match the pimonidazole retention patterns observed in vivo. Good agreement was obtained for multiple tumor models by optimizing the oxygen consumption rate, M0, whose optimum value differed significantly between tumor models.
Registration No. 25058 - Permalink

Local flow measurement in a continuous casting model test stand
Hernández, D.; Wondrak, T.; Karcher, C.
Abstract: Local Lorentz force velocimetry (LFV) is a contactless local velocity measurement technique for liquid metals. Due to the interaction between an electrically moving liquid and an applied magnetic field, eddy currents and flow-braking Lorentz forces are induced within the fluid. Due to Newton’s third law, a counter force of the same magnitude acts on the source of the applied magnetic field which is in our case a permanent magnet. The magnet is connected to a new generation force/torque sensor that has been especially developed to record all force and torque components. This sensor has already been tested at a continuous casting model with a 15 mm cubic magnet providing an insight of the 3-D velocity distribution of GaInSn near the wide face of the mold [1]. For a better understanding of these results, especially regarding torque sensing, we propose a kinematic approach of ohm’s law where the velocity field is already given. In this case we avoid the variability and noise of the measurements meaning that the force depends just on the velocity distribution of the liquid metal. In this paper we present a comparison between our numerical model and the previous experiments.
  • Contribution to proceedings
    Workshop Elektroprozesstechnik, 22.-23.09.2016, Ilmenau, Deutschland
  • Lecture (Conference)
    Workshop Elektroprozesstechnik, 22.-23.09.2016, Ilmenau, Deutschland
Registration No. 25056 - Permalink

Synthese von Transglutaminase 2-Inhibitoren und Präkursoren für deren Markierung mit Fluor-18
Bauer, D.
Abstract: Kein Abstract vorhanden
  • Master thesis
    TU Dresden, 2016
    Mentor: Dr. Reik Löser
    181 Seiten
Registration No. 25051 - Permalink

Germanium Recovery from Optical Fiber Waste
Recksiek, V.; Scharf, C.
Abstract: Germanium is an essential element for the European information technology. The increasing demand for high speed internet connections requires the application of optical fibers, which cannot be produced without Germanium. Because of high supply risks, the European Union added Germanium to the list of critical raw materials in 2010. The world refinery production of Germanium was approximately 165 metric tons in 2014. Thirty percent of this amount was used for the manufacturing of optical fibers. In the production process various Germanium containing scraps are generated, from some of these Germanium is not yet recovered.
This poster outlines methods for the recovery of Germanium from these waste materials. The necessary mechanical processing and a possible pyrometallurgical recovery process are discussed.

Keywords: Germanium, recovery, distillation, reduction, chlorination
  • Poster
    European Resources Forum, Nationales Ressourcen-Forum, 09.-11.11.2016, Berlin, Deutschland
  • Lecture (Conference)
    Aufbereitung und Recycling, 11.-12.11.2015, Freiberg, Deutschland
Registration No. 25050 - Permalink

Synthese Lysin-abgeleiteter Inhibitoren der Transglutaminase 2 als potentielle Radiotracer zur funktionellen Charakterisierung dieses Enzyms
Lohse, M.
Abstract: In der vorliegenden Bachelorarbeit wird die Synthese von irreversiblen Transglutaminase 2-Inhibitoren basierend auf einem N6-Acryloyl-L-lysin-Grundgerüst beschrieben. Dafür konnte ausgehend von einem N6-Acryloyl-L-lysin eine Reaktionssequenz aus den drei Schritten Amidkupplung, Boc-Entschützung und N2-Acylierung angewendet werden. Auf diesem Weg erfolgte die Synthese von 23 Inhibitoren mit einer Gesamtausbeute zwischen 2% und 17%. Die Inhibitoren sollen für die Ermittlung von Struktur-Aktivitätsbeziehungen sowie als Vorläuferverbindungen und Referenzverbindungen für PET-Radiotracer verwendet werden.
Weiterhin wird die Synthese eines Fluorophor-konjugierten Substrats der TGase 2 beschrieben. Die Festphasensynthese von 2’-((5-Aminopentyl)isonipecotyl)rhodamin B erfolgte durch eine dreistufige Synthese ausgehend von dem an das 2-Chlortritylchlorid-Harz angebundenen Cadaverin mit einer Gesamtausbeute von 24%. Diese Verbindung soll für ein Fluoreszenzpolarisations-Assay zur Ermittlung der inhibitorischen Potenz (IC50) der irreversiblen TGase 2-Inhibitoren verwendet werden.
  • Bachelor thesis
    Hochschule Zittau/Görlitz, 2016
    Mentor: Dr. Reik Löser
    147 Seiten
Registration No. 25048 - Permalink

Molecular Targeting of Integrins and Integrin-Associated Signaling Networks in Radiation Oncology.
Vehlow, A.; Storch, K.; Matzke, D.; Cordes, N.
Abstract: Radiation and chemotherapy are the main pillars of the current multimodal treatment concept for cancer patients. However, tumor recurrences and resistances still hamper treatment success regardless of advances in radiation beam application, particle radiotherapy, and optimized chemotherapeutics. To specifically intervene at key recurrence- and resistance-promoting molecular processes, the development of potent and specific molecular-targeted agents is demanded for an efficient, safe, and simultaneous integration into current standard of care regimens. Potential targets for such an approach are integrins conferring structural and biochemical communication between cells and their microenvironment. Integrin binding to extracellular matrix activates intracellular signaling for regulating essential cellular functions such as survival, proliferation, differentiation, adhesion, and cell motility. Tumor-associated characteristics such as invasion, metastasis, and radiochemoresistance also highly depend on integrin function. Owing to their dual functionality and their overexpression in the majority of human malignancies, integrins present ideal and accessible targets for cancer therapy. In the following chapter, the current knowledge on aspects of the tumor microenvironment, the molecular regulation of integrin-dependent radiochemoresistance and current approaches to integrin targeting are summarized.
Keywords: Focal adhesion signaling; Integrins; Molecular targeting; Radiochemosensitization
  • Book chapter
    Baumann, M.; Krause, M.; Cordes, N: Molecular Radio-Oncology, Volume 198 of the series Recent results in Cancer Research, Berlin Heidelberg: Springer Verlag, 2016, 89-106
    DOI-Link: http://dx.doi.org/10.1007/978-3-662-49651-0_4
Registration No. 25047 - Permalink

Optimisation of Cathepsin B Endopeptidase Substrates as Potential Cleavage Sites for Activatable Cell-Penetrating Peptides (ACPP)
Kuhne, K.; Behring, L.; Belter, B.; Wodtke, R.; Steinbach, J.; Pietzsch, J.; Löser, R.
Abstract: High activity of the cysteine protease cathepsin B correlates with increased metastasis, therapy resistance, and a generally poor prognosis in neoplastic diseases [1,2] Therefore, the development of substrate-based radiotracers for in vivo imaging of this protease will be beneficial towards better diagnosis and improved therapy regimens. We aim at developingsuch a probe by combination of a polyarginine-based, activatable cell penetrating peptide, as described by Tsien and others, and newly optimised endopeptidase substrates for cathepsin B [3]. A unique feature of cathepsin B within the cysteine cathepsin family is the occluding loop, a flexible element consisting of 20 amino acids (aa), which is able to cover the active site of the enzyme and thereby regulates the substrate specificity in a pH-dependent manner [1,2]. This phenomenon is mediated by two histidine residues within the occluding loop, which play a crucial role in positioning a potential substrate for carboxydipeptidolytic cleavage.
Starting point for the development of endopeptidase substrates was the carboxydipeptidase substrate Abz‑GIVRAK(Dnp)‑OH (Abz - aminobenzoyl, Dnp - dinitrophenyl) described by Cotrin et al. in 2004, with the fluorophores Abz and Dnp constituting a FRET pair to enable fluorometric detection of the proteolytic cleavage [4]. Two structural changes were introduced to convert the exopeptidase substrate into an endopeptidase substrate for later use as an activator sequence in an aCPP: Firstly, C‑terminal amidation was performed to interrupt the interaction between the terminal carboxyl group and the two His residues within the occluding loop. This resulted in a reduced specificity constant (kcat/Km = 1179 mM‑1s‑1 vs. 139 mM‑1s‑1), indicating attenuated electrostatic/hydrogen bond interactions. Secondly, the peptide sequence was C‑terminally elongated to test longer substrates. Interestingly, the C‑terminal elongation resulted in a hysteretic progress of the enzymatic cleavage, likely a result of the steric displacement of the occluding loop. To evaluate the influence of size, polarity and charge of the C‑terminal aa on the enzymatic hysteresis, 14 variations of this position were synthesized and analysed for their kinetic parameters. The peptide Abz‑GIVRAK(Dnp)G‑V‑NH2 was determined to exhibit the highest specificity constant (kcat/Km = 260 mM‑1s‑1).
The optimised octapeptide sequence is currently inserted as recognition site in a fluorophore-labelled aCPP for monitoring cathepsin B-mediated activation and subsequent cellular uptake, and for investigating kinetics and in vitro stability analysis in future
experiments.
[1] Aggarwal and Sloane, Proteomics Clin. Appl. 2014, 8(5-6), 427-437
[2] Löser and Pietzsch, Front. Chem. 2015, 3, article 37
[3] Jiang et al., PNAS, 2004, 101(51), 17867-17872
[4] Cotrin et al., Anal. Biochem. 2004, 335, 244-252
  • Poster
    34th European Peptide Symposium, 04.-09.09.2016, Leipzig, Deutschland
  • Abstract in refereed journal
    Journal of Peptide Science 22(2016)S2, 177-178
    DOI-Link: http://dx.doi.org/10.1002/psc.2950
    Button zum Volltext

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Registration No. 25046 - Permalink

N6-Acryloyl-lysine piperazides as irreversible inhibitors of transglutaminase 2 - synthesis and structure activity relationships
Wodtke, R.; Jäckel, E.; Wong, A.; Lohse, M.; Bauer, D.; Ullm, S.; Steinbach, J.; Pietzsch, J.; Löser, R.
Abstract: Various kinds of tumour entities are characterised by an increased activity of transglutaminase 2 (TGase 2), which contributes to an enhanced invasive potential of the tumour cells and their resistance to chemo- and radiotherapy. Therefore, this enzyme represents an interesting target for the development of PET tracers for functional imaging of tumours in vivo [1].
Among the TGase 2 inhibitors described in the literature, N6-acryloyl-lysine-4-arylpiperazides reported by Wityak et al. [2] seem to be most suitable for radiotracer development as these compounds exhibit both strong inhibitory potential and selectivity towards human TGase 2 and show favourable pharmacokinetic properties. Based on this class of compounds, derivatives that allow for labelling with radionuclides such as fluorine-18 and iodine-124 were prepared and their inhibitory potential towards TGase 2 was evaluated.
The N2-acyl-N6-acryloyl-lysine-4-pyridylpiperazides were synthesised in a sequence consisting of N6-acrylation, PyBOP-mediated amide bond formation, Boc deprotection and N2-acylation starting from N2-Boc-lysine. The required pyridylpiperazines were obtained commercially or prepared in a few steps. All final compounds were evaluated in two independent kinetic assays, which detect either the transamidase or hydrolase activity of TGase 2, respectively, with N2-phenylacetyl-N6-acryloyl-lysine-4-(6-methylpyridine-2-yl)piperazide [2] serving as benchmark inhibitor.
Using the outlined synthetic route a series of more than 40 N2-acyl-N6-acryloyl-lysine-4-pyridylpiperazides were prepared in good yields. The kinetic characterisation of the compounds revealed some interesting structure-activity relationships. For example, replacing the 6-methylpyridine-2-yl moiety of the benchmark inhibitor by a 2-nitro-5-pyridyl moiety led to a significantly increased inhibitory effect towards human TGase 2.
Furthermore, substitution of the methyl group by hydrogen or a halogen atom (F, Cl, Br and I) revealed a direct correlation between the van der Waals radius of the substituent and the inhibitory effect towards human TGase 2, with the inhibitor containing iodine being even more potent than the benchmark inhibitor. Covalent docking studies provided information about the binding mode of this inhibitor class for the first time and, thus, allowed for explaining the trends observed in the activity assays and give hints for further improvement of inhibitory potency by specific structural variations.
References:
[1] Pietsch etal. Bioorg. Med. Chern. Lett. 2013, 23, 6528. [2] Wityak etal. ACS Med. Chem. Lett. 2012, 3, 1024.
  • Poster
    Frontiers in Medicinal Chemistry, 13.-16.03.2016, Bonn, Deutschland
Registration No. 25045 - Permalink

Erbium ion implantation into diamond – measurement and modelling of the crystal structure
Cajzl, J.; Nekvindová, P.; Mackova, A.; Malinský, P.; Sedmidubsky, D.; Hušák, M.; Remeš, Z.; Varga, M.; Kromka, A.; Böttger, R.; Oswald, J.
Abstract: Diamond is proposed as extraordinary material usable for interdisciplinary fields, especially for optics and photonics. In this contribution we focus on the doping of diamond with erbium as optically active centre. In the theoretical part of study based on DFT simulations we have developed two Er-doped diamond structure models with 0 to 4 carbon vacancies in the vicinity of Er atom and performed geometry optimizations with calculation of cohesive energies and defect formation energies. The theoretical results showed an excellent agreement between the calculated and experimental cohesive energy for the parent diamond. The highest values of cohesive energies and lowest values of defect formation energies were obtained for models with erbium in the substitutional carbon position with 1 or 3 vacancies in the vicinity of erbium atom. From the geometry optimization the structure model with 1 vacancy had an octahedral symmetry whereas the model with 3 vacancies had a coordination of 10 forming a trigonal structure with hexagonal ring. In the experimental part, erbium doped diamond crystal samples were prepared by ion implantation of Er+ ions using ion implantation fluences ranging from 1×1014 ions/cm2 to 5×1015 ions/cm2. The experimental results revealed a high degree of diamond structure damage after the ion implantation process reaching up to 69% of disordered atoms in the samples. The prepared Er-doped diamond samples annealed at the temperatures of 400, 600 and 800 °C in vacuum revealed clear luminescence, where the 〈110〉 cut sample was having approximately 6-7 times higher luminescence intensity than 〈001〉 cut sample with the same ion implantation fluence. The reported results are the first demonstration of the Er luminescence in the single crystal diamond structure for the near-infrared spectral region.
Keywords: diamond, erbium, ion implantation, luminescence, DFT Registration No. 25044 - Permalink

Evaluation of tumour hypoxia during radiotherapy using [18F]HX4 PET imaging and blood biomarkers in patients with head and neck cancer
Zegers, C. M. L.; Hoebers, F. J. P.; van Elmpt, W.; Bons, J. A.; Öllers, M. C.; Troost, E. G. C.; Eekers, D.; Balmaekers, L.; Arts-Pechtold, M.; Mottaghy, F. M.; Lambin, P.
Abstract: BACKGROUND AND PURPOSE:

Increased tumour hypoxia is associated with a worse overall survival in patients with head and neck squamous cell carcinoma (HNSCC). The aims of this study were to evaluate treatment-associated changes in [18F]HX4-PET, hypoxia-related blood biomarkers, and their interdependence.
MATERIAL AND METHODS:

[18F]HX4-PET/CT scans of 20 patients with HNSCC were acquired at baseline and after ±20Gy of radiotherapy. Within the gross-tumour-volumes (GTV; primary and lymph nodes), mean and maximum standardized uptake values, the hypoxic fraction (HF) and volume (HV) were calculated. Also, the changes in spatial uptake pattern were evaluated using [18F]HX4-PET/CT imaging. For all patients, the plasma concentration of CAIX, osteopontin and VEGF was assessed.
RESULTS:

At baseline, tumour hypoxia was detected in 69 % (22/32) of the GTVs. During therapy, we observed a significant decrease in all image parameters. The HF decreased from 21.7 ± 19.8 % (baseline) to 3.6 ± 10.0 % (during treatment; P < 0.001). Only two patients had a HV > 1 cm3 during treatment, which was located for >98 % within the baseline HV. During treatment, no significant changes in plasma CAIX or VEGF were observed, while osteopontin was increased.
CONCLUSIONS:

[18F]HX4-PET/CT imaging allows monitoring changes in hypoxia during (chemo)radiotherapy whereas the blood biomarkers were not able to detect a treatment-associated decrease in hypoxia.

Keywords: CAIX; Hypoxia; Osteopontin; PET; VEGF

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Registration No. 25043 - Permalink

Synthese und enzymkinetische Prüfung von N6-Acryloyllysinpiperaziden als potentielle Radiotracer zur Bildgebung der Transglutaminase 2 (TGase 2)
Wodtke, R.; Hauser, C.; Jäckel, E.; Ruiz-Gomez, G.; Ullm, S.; Wong, A.; Lohse, M.; Steinbach, J.; Pietzsch, J.; Pietsch, M.; Löser, R.
Abstract: Ziel/Aim: Zahlreiche Krebsarten zeichnen sich durch eine deutlich erhöhte Aktivität der TGase 2 aus, die vor allem mit einer gesteigerter Chemo- und Strahlenresistenz der Krebszellen korreliert. Daher stellt dieses Enzym ein interessantes Target für die Entwicklung von PET-Tracern zur funktionellen Bildgebung derartiger Tumoren dar. Unter den bekannten Inhibitoren der TGase 2 erscheinen die N6-Acryloyllysin-4-arylpiperazide für die Entwicklung von Radiotracern als besonders geeignet, da sie über eine hohe inhibitorische Potenz und Selektivität verfügen (1). Daher sollten ausgehend von dieser Verbindungsklasse Derivate zugänglich gemacht werden, die eine Markierung mit Radionukliden wie F-18 oder Radioiod erlauben.
Methodik/Methods: Ausgehend von N2-Boc-Lysin wurden in einer Sequenz bestehend aus N6-Acrylierung, Amidknüpfung, Boc-Entschützung und N2-Acylierung verschiedene N2-Acyl-N6-acryloyllysin-4-arylpiperazide synthetisiert. Alle Zielverbindungen wurden in zwei unabhängigen enzymkinetischen Assays, welche die Transamidase- bzw. Hydrolaseaktivität der TGase 2 erfassen, evaluiert.
Ergebnisse/Results: Bisher wurde eine Serie von mehr als 40 Inhibitoren synthetisiert, deren enzymkinetische Charakterisierung interessante Struktur-Wirkungsbeziehungen aufdeckte. So führt der Ersatz des 6-Methyl-2-pyridyl-Restes im literaturbekannten Referenzinhibitor N2-Phenylacetyl-N6-acryloyllysin-4-(6-methylpyridin-2-yl)piperazid gegen einen 2-Nitro-5 pyridyl-Rest zu einer deutlich höheren Hemmwirkung gegenüber der TGase 2. Untersuchungen zum kovalenten Docking der Inhibitoren im aktiven Zentrum der TGase 2 geben erstmals Aufschluss über deren Bindungsmodus.
Schlussfolgerungen/Conclusions: Die gefundenen Struktur-Wirkungs-Beziehungen können gezielt genutzt werden, um potentielle Radiotracer hinsichtlich ihrer Hemmkinetik zu verbessern, was für ihre Anwendung zur molekularen Bildgebung in vivo vorteilhaft ist.
Literatur/References:
[1] Wityak et al. ACS Med. Chem. Lett. 2012, 3, 1024.
  • Poster
    54. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin, 20.-23.04.2016, Dresden, Deutschland
  • Abstract in refereed journal
    Nuklearmedizin 55(2016)2, A77-A77
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Registration No. 25042 - Permalink

Simulating laser wakefield acceleration with PIConGPU - from modeling the laser plasma dynamic to in-situ radiation calculation
Pausch, R.; Debus, A.; Burau, H.; Huebl, A.; Garten, M.; Steiniger, K.; Widera, R.; Bussmann, M.; Schramm, U.
Abstract: We recent simulations of laser wakefield acceleration on recent experiments performed at HZDR. We focus on how to best approximate the experimental setup using newly developed laser-models, as well as particle creation- and ionization-methods. Furthermore, we elaborate on predicting experimentally observable radiation signatures from the simulation.

We discuss in detail the influence of various ionization mechanisms, including BSI, ADK and Keldysh, and how to model the initial gas or plasma distribution. Furthermore, we present recent improvements in the laser implementation, that added Laguerre-Gauss modes, which drastically reduces discrepancies between previous simulations and experiments. On top of simulating plasma dynamics, we present how to predict experimental observables using PIConGPU’s in-situ synthetic diagnostics, especially the classical Liénard-Wiechert potential- and QED-based radiation. It allows predicting both coherent and incoherent radiation spectrally from infrared to x-rays and provides the capability to resolve the radiation polarization as well as determine its temporal and spatial origin.

On the examples of a large-scale LWFA simulation, we illustrate how we reduce the gap between simulated plasma dynamics and radiation observed in experiments and discuss valuable spectral signatures which allow conclusions on the micrometer femtosecond electron dynamics occurring during acceleration.

Keywords: PIConGPU, LWFA, radiation, GPU, ionization, laser, synthetic diagnostics
  • Poster
    3rd Annual Matter and Technologies Meeting, Darmstadt 2017, 30.01.-02.02.2017, Darmstadt, Deutschland
  • Lecture (Conference)
    3rd Annual Matter and Technologies Meeting, Darmstadt 2017, 30.01.-02.02.2017, Darmstadt, Deutschland
Registration No. 25041 - Permalink

Multiscale structured germanium nanoripples as templates for bioactive surfaces
Dell'Anna, R.; Masciullo, C.; Iacob, E.; Barozzi, M.; Giubertoni, D.; Böttger, R.; Cecchini, M.; Pepponi, G.
Abstract: Nanostructured germanium substrates are produced by gold ion implantation; they show periodic ripples of nanometer size, decorated on the top and partially on one side with a forest of curled nanowires that end with gold-rich nanoparticles. For the first time, through a novel two-step soft lithography transfer process, the multi-scale nanopatterns are replicated, with features well below 100 nm, on biocompatible 2-norbornene ethylene cyclic olefin copolymer substrates. Given the suitable aspect ratio of the nanoripples and the peculiarity of their multiscale structure, the final substrates are available for cell–material interaction studies that can shed light on the role of the hierarchy of nanostructured materials in controlling the large-scale cellular behavior on biocompatible scaffolds. This work also presents an original combination of numerical analyses of scanning force microscopy images, which allows an accurate quantitative description of the outputs of the two-step transfer process.
Keywords: nanostructures, germanium, ion irradiation, lithography, transfer process Registration No. 25040 - Permalink

Impact of pre- and early per-treatment FDG-PET based dose-escalation on local tumour control in fractionated irradiated FaDu xenograft tumours.
Jentsch, C.; Bergmann, R.; Brüchner, K.; Mosch, B.; Yaromina, A.; Krause, M.; Zips, D.; Troost, E. G. C.; Löck, S.; Kotzerke, J.; Steinbach, J.; Thames, H.; Baumann, M.; Beuthien-Baumann, B.
Abstract: OBJECTIVE:

To investigate local tumour control after dose-escalation based on [18F]2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) obtained before and early during fractionated irradiation.
MATERIALS AND METHODS:

85 mice bearing FaDu xenografts underwent FDG-PET twice: first immediately prior to the first 2-Gy fraction of irradiation (PET1_0) and second after 18°Gy (PET2_18). After these 9 fractions, animals were randomly allocated to: (1) continuation of 2-Gy fractions (cumulative dose of 60°Gy; n=31), (2) dose-escalation with 3-Gy fractions (cumulative EQD2-dose 86.25°Gy [α/β-value: 10]; n=25), or (3) with 4-Gy fractions (cumulative EQD2-dose 116°Gy; n=29). The effects of SUVmax0°Gy, SUVmax18°Gy, and dose on local tumour control were analysed in two ways. First, the Cox proportional hazards model was used with two covariates: continuous SUVmax values and dose. Second, the Kaplan-Meier method was used, with tumours classified according to SUVmax greater than or less than (1) median maximum standardized uptake value (SUVmax) at PET1_0 and PET2_18, or (2) the cut-off value 2.5.
RESULTS:

The multivariate Cox analysis revealed a significant negative association between higher SUVmax determined before start of treatment and local control (HR=1.59, [95% CI 1.04, 2.42], p=0.031), whereas higher dose had a significant positive effect (HR=0.95, [0.93, 0.98], p<0.001). In contrast, FDG uptake at 18Gy did not correlate with local control (HR=1.14, [0.53, 2.45], p=0.73). Neither FDG uptake prior to irradiation nor at 18Gy correlated with local control irrespective of the delivered dose (log-rank test) when using the median SUVmax values for stratification (SUVmax0Gy: 60Gy: p=0.25, 86.25Gy: p=0.47, 116Gy: p=0.88 and SUVmax18Gy: 60Gy: p=0.42, 86.25Gy: p=0.34, 116Gy: p=0.99). By contrast, stratifying the animals by the cut-off 2.5 at PET1_0 reveals a significant difference in local control for the 60Gy group (p=0.034), but not for the other dose groups. At PET2_18, no significant effect for any dose group was detected.
CONCLUSIONS:

The multivariate Cox analysis revealed a significantly higher hazard of recurrence for mice with higher SUVmax determined before start of treatment. These results support the hypothesis that patients with high pre-therapeutic FDG uptake should be considered at increased risk of local failure and therefore as possible candidates for dose escalation strategies.

Keywords: Dose escalation; FDG positron emission tomography; FaDu xenografts; Fractionated irradiation; Local tumour control; Squamous cell carcinoma Registration No. 25039 - Permalink

HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).
Linge, A.; Lohaus, F.; Löck, S.; Nowak, A.; Gudziol, V.; Valentini, C.; von Neubeck, C.; Jütz, M.; Tinhofer, I.; Budach, V.; Sak, A.; Stuschke, M.; Balermpas, P.; Rödel, C.; Grosu, A. L.; Abdollahi, A.; Debus, J.; Ganswindt, U.; Belka, C.; Pigorsch, S.; Combs, S. E.; Mönnich, D.; Zips, D.; Buchholz, F.; Aust, D. E.; Baretton, G. B.; Thames, H. D.; Dubrovska, A.; Alsner, J.; Overgaard, J.; Krause, M.; Baumann, M.
Abstract: OBJECTIVE:

To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received primary radiochemotherapy (RCTx).
MATERIALS AND METHODS:

For 158 patients with locally advanced HNSCC of the oral cavity, oropharynx or hypopharynx who were treated at six DKTK partner sites, the impact of tumour volume, HPV DNA, p16 overexpression, p53 expression, CSC marker expression and hypoxia-associated gene signatures on outcome of primary RCTx was retrospectively analyzed. The primary endpoint of this study was loco-regional control (LRC).
RESULTS:

Univariate Cox regression revealed a significant impact of tumour volume, p16 overexpression, and SLC3A2 and CD44 protein expression on LRC. The tumour hypoxia classification showed a significant impact only for small tumours. In multivariate analyses an independent correlation of tumour volume, SLC3A2 expression, and the 15-gene hypoxia signature with LRC was identified (CD44 protein n/a because of no event in the CD44-negative group). Logistic modelling showed that inclusion of CD44 protein expression and p16 overexpression significantly improved the performance to predict LRC at 2years compared to the model with tumour volume alone.
CONCLUSIONS:

Tumour volume, HPV status, CSC marker expression and hypoxia gene signatures are potential prognostic biomarkers for patients with locally advanced HNSCC, who were treated by primary RCTx. The study also supports that the individual tumour volumes should generally be included in biomarker studies and that panels of biomarkers are superior to individual parameters.

Keywords: Biomarkers for radiotherapy; Cancer stem cells; HNSCC; HPV; Hypoxia; Primary radiochemotherapy Registration No. 25037 - Permalink

Internal and external validation of an ESTRO delineation guideline - dependent automated segmentation tool for loco-regional radiation therapy of early breast cancer.
Eldesoky, A. R.; Yates, E. S.; Nyeng, T. B.; Thomsen, M. S.; Nielsen, H. M.; Poortmans, P.; Kirkove, C.; Krause, M.; Kamby, C.; Mjaaland, I.; Blix, E. S.; Jensen, I.; Berg, M.; Lorenzen, E. L.; Taheri-Kadkhoda, Z.; Offersen, B. V.
Abstract: BACKGROUND AND PURPOSE:

To internally and externally validate an atlas based automated segmentation (ABAS) in loco-regional radiation therapy of breast cancer.
MATERIALS AND METHODS:

Structures of 60 patients delineated according to the ESTRO consensus guideline were included in four categorized multi-atlas libraries using MIM Maestro™ software. These libraries were used for auto-segmentation in two different patient groups (50 patients from the local institution and 40 patients from other institutions). Dice Similarity Coefficient, Average Hausdorff Distance, difference in volume and time were computed to compare ABAS before and after correction against a gold standard manual segmentation (MS).
RESULTS:

ABAS reduced the time of MS before and after correction by 93% and 32%, respectively. ABAS showed high agreement for lung, heart, breast and humeral head, moderate agreement for chest wall and axillary nodal levels and poor agreement for interpectoral, internal mammary nodal regions and LADCA. Correcting ABAS significantly improved all the results. External validation of ABAS showed comparable results.
CONCLUSIONS:

ABAS is a clinically useful tool for segmenting structures in breast cancer loco-regional radiation therapy in a multi-institutional setting. However, manual correction of some structures is important before clinical use. The ABAS is now available for routine clinical use in Danish patients.

Keywords: Atlas based automated segmentation; Breast cancer; ESTRO consensus guideline; Multi-center study; Target volume delineation; Validation Registration No. 25035 - Permalink

Top-Down Fabrication and Characterization of SiNW RFETs
Deb, D.; Georgiev, Y.; Löffler, M.; Weber, W.; Helm, M.; Erbe, A.
Abstract: The following work illustrates top-down fabrication and characterization of reconfigurable, undoped silicon nanowire field effect transistors with Schottky junctions on silicon on insulator (SOI) substrate. The fabrication scheme is based on electron beam lithography (EBL) on a SOI substrate followed by reactive ion etching (RIE) with HSQ etch mask. In best case we fabricated nanowires with 20 nm width and 60 nm pitch.
Nickel-silicide Schottky junctions were created inside the nanowire by ni-sputtering followed by forming gas annealing. Diffusion of nickel in silicon nanowire is precisely controlled by optimizing the time of annealing. Detailed morphological analyses of the nanowires were done by transmission electron microscopy (TEM) at Dresden Center for Nanoanalysis to identify the strained deformation in silicon crystal structure due to silicidation.

Keywords: EBL, ICP, SiNW, RFETs
  • Lecture (Conference)
    IHRS NanoNet Annual Workshop 2015, 02.10.2015, Bastei, Germany
Registration No. 25033 - Permalink

Top-down fabrication and characterization of reconfigurable silicon nanowires
Deb, D.; Khan, M. B.; Georgiev, Y.; Löffler, M.; Weber, W.; Helm, M.; Erbe, A.
Abstract: The following work illustrates characterization of reconfigurable, undoped silicon nanowire field effect transistors with Schottky junctions fabricated on silicon on insulator (SOI) substrate by top-down process. The fabrication scheme is based on electron beam lithography (EBL) using hydrogen silsesquioxane (HSQ), a negative tone electron beam resist, followed by inductively coupled plasma (ICP) etching. The etch recipe was optimised in context of selectivity, sidewall roughness and anisotropy by selecting an appropriate gas chemistry (SF6/C4F8) and controlling the ICP hardware parameters like gas flow, mixed gas ratio, plasma power and chamber pressure. We produced silicon nanowires of 20 nm width and nanowire arrays with pitch of 200 nm. 50 nm thick nickel (Ni) layer was sputtered on the SiNWs at lithographically defined areas followed by lift-off and thermal annealing to create Nickel-Silicide Schottky junctions inside the nanowires. In this way, the source and drain region was formed creating silicide-silicon-silicide contacts. Transport properties of these nanowires can be modulated from P-type to N-type and vice-versa by changing polarity of the back gate
Keywords: RFETs, ICP etching, EBL, Silicon nanowire, HSQ resist
  • Lecture (Conference)
    DPG Frühjahrstagung 2016, 06.-11.03.2016, Regensburg, Germany
Registration No. 25032 - Permalink

Analysis of NixSiy-Si Nanowires for Next Generation Electronics
Loffler, M.; Deb, D.; Muhle, U.
Abstract: Si Nanowires are one of the foremost candidates for “beyond CMOS” technology, both from the point of miniaturization (more Moore) but also from the point of added function (more-than-Moore). NiSi2-Si Schottky junctions in nanowires are the building blocks for the design of reconfigurable logic on the hardware level [1]. However, the device parameters depend very sensitively on the geometry of the interface and the transistor makeup.
Here we present the analysis of NixSiy-Si nanowires fabricated on silicon-on-insulator (SOI) substrate using a top-down approach and silicidized using thermal Ni diffusion from lithographically patterned electrodes. We employed both SEM and TEM techniques to identify regions of interest to be prepared by the standard FIB technique followed by 1kV FIB cleaning to preserve the crystal structure.
We observed that the interface forms {111} facets (Figure 1). Furthermore, we observed grain boundaries, nanotwins and multiple silicide phases between the Ni source and the Si part of the nanowire.

Keywords: TEM, RFETs, Nanaowires
  • Poster
    Scandem 2016, 07.-10.06.2016, Trondheim, Norway
Registration No. 25031 - Permalink

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