Publication database - Helmholtz-Zentrum Dresden-Rossendorf

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27505 Publications
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

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

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

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

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

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

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
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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

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

Characterization of silicon nanowires with NiSi2 Schottky contacts fabricated by top-down process
Deb, Dipjyoti; Fuchs, F.; Georgive, Y. M.; Gemming, S.; Schuster, J.; Erbe, A.
Abstract: We report on characterization of reconfigurable, undoped silicon nanowire field effect transistors (FETs) with an axial heterostructure (metal/intrinsic-silicon/metal) fabricated on silicon on insulator (SOI) substrates by top-down process. Reconfigurable Si nanowire transistors with Schottky junctions can be reversely configured as p-FET or n-FET simply by the application of back gate electric signal. 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. We produced silicon nanowires of 20 nm width and nanowire arrays with a pitch of ≈ 200 nm.
Nickel was sputtered on the Si nanowires at lithographically defined areas followed by thermal annealing to create nickel-silicide Schottky junctions inside the nanowires which also act as source-drain contacts. Diffusion of Ni in Si nanowires was precisely controlled by the radial crystal orientation of the nanowires, which was checked by transmission electron microscopy (TEM). TEM images show atomic sharp NiSi2-silicon junctions. Quantum transport simulations using non-equilibrium Green’s functions show changes in local density of states at the NiSi2-Si interface. Calculations also confirm that at the NiSi2-Si junction the Schottky barrier, heights for electron and holes are equal.

Keywords: NiSi2, Schottky Junctions, TEM
  • Poster
    Physics on Boat 2016, 31.05.-02.06.2016, Helsinki, Finland
Registration No. 25030 - Permalink

Top-down fabrication and characterization of reconfigurable silicon nanowire-based field effect transistors with Schottky contacts
Deb, D.; Khan, M. B.; Georgiev, Y. M.; Löffler, M.; Weber, W.; Helm, M.; Erbe, A.
Abstract: In the last 60 years the size of a transistor has been reduced from few centimeters to few nanometers. Smarter, faster and cheaper: these are the three factors that motivated the miniaturization crusade in the silicon chip industry. Now we reach the end of physical scaling and it is expected that future development will be based on new ideas1: (i) new materials (high-mobility channel materials accompanied by metal gates with high-k gate dielectrics), (ii) new architectures (e.g. 3D integration), (iii) new functionality (e.g. reconfigurability), (iv) new computation principles (e.g. spintronics, quantum computing), etc.
In this work we deal with this problem by introducing reconfigurability in transistors. We report on characterization of reconfigurable, undoped silicon nanowire field effect transistors (FETs) with Schottky junctions fabricated on silicon on insulator (SOI) substrates by an industry compatible top-down process. Reconfigurable transistors employ an axial nanowire heterostructure (metal/intrinsic-silicon/metal) with independent gating of the two Schottky junctions and can be reversely configured as p-FET or n-FET simply by the application of an electric signal2.
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 optimized with respect to selectivity, sidewall roughness and anisotropy by selecting an appropriate gas chemistry (SF6/C4F8) and controlling the ICP hardware parameters such as gas flow, mixed gas ratio, plasma power and chamber pressure. We produced silicon nanowires of 20 nm width and nanowire arrays with a pitch of ≈ 200 nm.
A nickel (Ni) layer of 50 nm thickness was sputtered on the Si nanowires 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 regions were formed creating silicide-silicon-silicide contacts. Diffusion of Ni in Si nanowires was precisely controlled by the radial crystal orientation of the nanowires, which was checked by transmission electron microscopy (TEM). The Schottky junctions were electrostatically modulated by a back gate potential. Transport properties of these nanowires could be switched from p-type to n-type and vice-versa by changing the polarity of the back gate.

References
1. L. Risch, Solid-State Electronics. 50, 527 (2006).
2. A. Heinzig, T. Mikolajick, J. Trommer, D. Grimm and W. M. Weber, Nano Letters. 13, 4176 (2013).

Keywords: Nanowires, FETs, Schotky Junctions, Silicides
  • Lecture (Conference)
    ICSNN 2016 - 19th International Conference on Superlattices, Nanostructures and Nanodevices, 25.-29.07.2016, Hong Kong, China
Registration No. 25029 - Permalink

Characterisation of top-down fabricated NixSiy-Si hetrostructure undoped nanowires
Deb, D.; Loffler, M.; Khan, M. B.; Georgiev, Y. M.; Erbe, A.
Abstract: Semiconductor industry reaches the end of physical scaling soon and it is expected that future development will be based on new concepts: (i) new materials (high-mobility channel materials accompanied by metal gates with high-k gate dielectrics), (ii) new architectures (e.g. 3D integration), (iii) new functionality (e.g. reconfigurability), (iv) new computation principles (e.g. spintronics, quantum computing), etc [1]. In our work we focus on new functionality, specifically reconfigurable logic. The most promising industry compatible hardware for this logic is silicon nanowire based Schottky junction FET [2]. However, NiSi2-Si Schottky junctions in axial heterostructures (metal/intrinsic silicon/metal) are still complex and detailed studies of these structures are essential.
We report on heterostructure (NixSiy-Si) characterisation of reconfigurable, undoped silicon nanowire Schottky junction FETs. The nanowires are fabricated on silicon on insulator (SOI) substrates by electron beam lithography (EBL) using hydrogen silsesquioxane (HSQ), a negative-tone electron beam resist, followed by inductively-coupled plasma (ICP) etching. We produced silicon nanowires of 20 nm width and arrays of them with a pitch of ≈ 200 nm. Nickel was sputtered on the Si nanowires at lithographically defined areas followed by thermal annealing to create nickel-silicide Schottky junctions inside the nanowires, which also act as source-drain contacts. Silicidation was done on single nanowires and nanowire arrays with varying cross-sections and also for different annealing times.
We investigated the corresponding devices using SEM and TEM concerning their morphology and silicidation and determined the necessary parameters to allow for a reproducible scaling of these structures.
Furthermore, some cross-sections of nanowire samples were prepared by the standard FIB technique followed by low voltage FIB cleaning to preserve the crystal structure. We observed that the interface between the Ni silicide and the intrinsic silicon forms {111} facets. In contrast to common expectations, also features such as grain boundaries, nanotwins and multiple silicide phases between the Ni source and the Si part of the nanowire have been observed. Those features pose a technological challenge towards large-scale integration in future reconfigurable semiconductor devices and need to be properly studied and taken into account.
[1] L. Risch, Solid-State Electronics. 50 (2006) 527-535.
[2] A. Heinzig, T. Mikolajick, J. Trommer, D. Grimm and W. M. Weber, Nano Lett. 13 (2013) 4176-4181.

Keywords: Nanowires, TEM, silicon on insulator, Schottky junction, FETs, Silicidation
  • Poster
    42nd Micro and Nano Engineering international conference (MNE 2016), 19.-23.09.2016, Vienna, Austria
Registration No. 25028 - Permalink

Open volume defects in annealed and ion irradiated SrTiO3 systems
Liedke, M. O.; Potzger, K.; Srinivasan, N.; Wagner, A.
Abstract: The formation of vacancies in SrTiO3 due to annealing in vacuum [1] or low-energy ion irradiation [2] also leads to the modification of electronic properties that could be exploited in applications like resistivity switching. Here, we employ both these modification methods combined with in-situ defects evolution analysis by means of Doppler Broadening Positron Annihilation Spectroscopy (DB-PAS). Two reference SrTiO3 single crystals, undoped and Nb-doped have been investigated. Vacuum annealing of undoped SrTiO3 increases the defect concentration which can be attributed to the creation of oxygen and strontium vacancies close to the sample surface and deeper inside the substrate, respectively. Variable energy DB-PAS reveals the depth-dependent open volume defects concentration. Second, in-situ room and low temperature (about 165K) Ar+ irradiation has been utilized as a preliminary attempt to understand a vacancy migration process beneath the kinetical ion penetration depth. For that purpose, a frozen vacancy state is required, which could be achieved by lowering the system temperature below the vacancy activation energy. Although, that part of the experiment has been not entirely successful due to not low enough temperature realized during ion irradiation, however, a strong conclusion has been drawn about necessity of performing such type of experiments in-situ. A clear indication of oxygen deficiency at the sample surface due to ion irradiation, as found from DB-PAS is diminished after repeated ex-situ measurements.
Keywords: strontium titanate, annealing, PAS, Doppler broadening, AIDA
  • Poster
    MEMRIOX International Workshop 2016, 25.-27.09.2016, Bastei, Germany
Registration No. 25027 - Permalink

Positron annihilation spectroscopy of ion and laser irradiation driven spin reorientation transitions in Pt/Co/Pt systems
Liedke, M. O.; Sveklo, I.; Jakubowski, M.; Anwand, W.; Yuan, Y.; Zhou, S.; Kurant, Z.; Wawro, A.; Maziewski, A.; Wagner, A.
Abstract: Multilayer ultrathin-films with perpendicular magnetic anisotropy (PMA) show a perspective as candidates for spintronic devices. The effective magnetic anisotropy strongly depends on the magnetic layer thickness – spin reorientation transition (SRT) at a critical thickness takes place from the inplane to out-of-plane magnetization direction. Moreover, SRT can be shifted to higher thicknesses by means of ion [1] and fs-laser irradiation [2]. Here, we employ variable energy positron annihilation spectroscopy (PAS) that is sensitive to open volume defects and their atomic surrounding to compare these two methods of the SRT inducement. Molecular beam epitaxy deposited films with different bottom Pt layer thicknesses and growth temperatures have been investigated. In case of Ar+ ion irradiated trilayers magnetization can be driven to the out-of-plane state twice as a function of ion fluence [1], whereas our preliminary studies of UV laser irradiation suggest only one SRT.
PAS analysis (Fig. 1) of the as-grown samples reveal slight differences in crystal quality and defect concentration that is likely due to a thicker bottom Pt layer used for the ion irradiation experiment.
Films utilized for the laser irradiation exhibit larger initial positron diffusion length, L+ that is close to L+ of the substrate (~60nm). In case of lower ion and laser fluences only minor and no interface intermixing has been found, respectively. The sample irradiated with lower ion fluence shows a slight increase of S (for E~1.5keV) being likely due to Co-vacancy increase, which could be responsible for first SRT. The sample irradiated with lower laser fluence shows no difference compare to the asgrown stacks, where only increase of magnetic anisotropy was found. The larger ion and laser fluences reorients magnetization to the out-of-plane state that is evidenced by both magneto-optical and PAS studies – S(E) curves nicely overlap. Moreover, large intermixing is expected, thus creation of the CoPt alloy with PMA. To elucidate stoichiometry and atomic surrounding of open volume defect coincidence Doppler broadening investigations will be presented.
*Corresponding author. E-mail address: m.liedke@hzdr.de
[1] A. Maziewski et al., Phys. Rev. B. 85, 054427 (2012)
[2] J. Kisielewski et al., J. Appl. Phys. 115, 053906 (2014)

Keywords: perpendicular magnetic anisotropy, positron annihilation spectroscopy, Doppler broadening, ion irradiation, UV ns-laser irradiation
  • Poster
    Joint European Magnetic Symposia (JEMS), 21.-26.08.2016, Glasgow, United Kligdom
Registration No. 25026 - Permalink

Positron annihilation lifetime spectroscopy study of self-assembled porous low-k films
Kraatz, M.; Clausner, A.; Gall, M.; Zschech, E.; Liedke, M. O.; Anwand, W.; Wagner, A.; Krause-Rehberg, R.; Pakbaz, K.
Abstract: We investigated advanced, self-assembled, porous organosilicate glasses with varying porogen level, resulting in varying dielectric constants (k-values ranging from 1.8 to 2.7, including a non-porous reference sample with 3.0). We used positron annihilation lifetime spectroscopy (PALS) to determine the pore size. The pores are fabricated by self-assembly into the OSG by a sol-gel process. The pore size is a critical parameter to characterize the quality of the OSG thin film. Other critical parameters, which were not investigated in this study are connectedness of pores and pore size distribution. Porous OSG is used in the microelectronic industry as insulating material for the wiring of microchips. Since pores not only lower the k-value, but also degrade mechanical stability of film stacks in microchips, knowledge of pore characteristics is crucial. Low-k materials are a necessity to lower microchip power consumption, maintain signal speed and reduce coupling in the relentless icroelectronics miniaturization process.
Keywords: positron annihilation spectroscopy, low-k, dielectrics, porous materials, positron lifetime
  • Poster
    14th International Conference Reliability and Stress-Related Phenomena in Nanoelectronics – Experiment and Simulation, 30.05.-01.06.2016, Bad Schandau, Germany
Registration No. 25025 - Permalink

P1608 - Ionenmikroskopievorrichtung
Klingner, N.; Heller, R.; Hlawacek, G.; Facsko, S.; von Borany, J.; Wilhelm, R. A.
Abstract: Die Erfindung betrifft eine Ionenmikroskopievorrichtung mit einer Ionenquelle zum Erzeugen eines Ionenstrahls, einem Detektor, einer Spannungsquelle und einem Photonenpuls-Generator, wobei die Ionenmikroskopievorrichtung zum Bestrahlen eines Objekts mit dem Ionenstrahl unter Erzeugung von Wechselwirkungsteilchen ausgebildet ist, wobei die Ionenquelle eine Gasionisationskammer, eine in derselben angeordnete spitzenförmige Elektrode und eine Gegenelektrode aufweist, der Detektor zum Erfassen der Wechselwirkungsteilchen dient, die Spannungsquelle zum Anlegen einer elektrischen Spannung zwischen die Elektrode und die Gegenelektrode dient, und der Photonenpuls-Generator zum Erzeugen von in die Ionisationskammer gerichteten Photonenpulsen dient.
  • Patent
    DE102016112328 - Erteilung: 05.01.2017
Registration No. 25024 - Permalink

Single Molecule Level Measurements
Kilibarda, F.; Ahmed, O.; Öktem, G.; Kiriy, A.; Cuniberti, G.; Erbe, A.
Abstract: In the quest for miniaturizing the transistor nodes, the technology does not look so promising and alternates have to be done in order to sustain the ‘Beyond CMOS’ trend. One of the promising technology can be the use of ‘Molecular Electronics’. In recent years, microelectronics industry is reaching its limits with transistor miniaturization. One of the possibilities is to abandon standard silicon technologies and start using single molecules and atoms as building blocks. By taking this route, it is first important to characterize and choose the right molecular candidates for future implementation. Till recent years this area was very slow in development, but as the techniques of electronic lithography, nanoscale manufacture and chemical synthesis continue to improve, it is accelerating in progress. In our research we are working with Mechanically Controlled Break Junctions (MCBJ) as a method of characterizing electrical properties of molecules and apply Landauer theoretical approach to model the behavior of the junctions. In parallel to that, we are examining possibilities to gate the molecules while they are being characterized. Our experiments show successful coupling to the molecules and accompanying change in conductance. In regard to gating we show possibility of manufacturing sub-20nm gaps for side gating of the molecular system.The developed techniques presented here may prove to be important in future many-level measurements and transistor implementation.
Keywords: Molecular electronics; MCBJ; electronic lithography; gating; nanogaps
  • Poster
    NanoNet International Workshop 2016, 30.08.-02.09.2016, Prague, Czech Republic
Registration No. 25023 - Permalink

P1511 - Thermisches Anemometer
Schleicher, E.; Berger, R.; Arlit, M.
Abstract: Die Erfindung betrifft ein thermisches Anemometer zum Charakterisieren einer Fluidströmung, wobei das Anemometer ein Sensorelement zum Einbringen in die Fluidströmung aufweist, das mittels einer Spannung elektrisch beheizbar ist; wobei das Anemometer zum abwechselnden Betreiben des Sensorelements mit einer kleineren ersten und einer größeren zweiten Spannung ausgebildet ist, sodass ein abwechselndes Erwärmen und Abkühlen des Sensorelements erfolgt; wobei beim Betreiben des Sensorelements mit der ersten Spannung beim Erreichen eines unteren Temperatur-Schwellenwertes ein Umschalten zu der zweiten Spannung erfolgt, beim Betreiben des Sensorelements mit der zweiten Spannung beim Erreichen eines oberen Temperatur-Schwellenwertes ein Umschalten zu der ersten Spannung erfolgt, und das Anemometer zum Charakterisieren der Fluidströmung basierend auf den Zeitabständen zwischen den Umschalt-Zeitpunkten, an denen ein Umschalten der Spannung erfolgt, ausgebildet ist.
  • Patent
    DE102015114139 - Erteilung: 08.12.2016
Registration No. 25022 - Permalink

The influence of local ion implantation on magnetic domains, magnetoresistance and spin wave propagation
Osten, J.; Hula, T.; Wagner, K.; Henschke, A.; Lenz, K.; Schultheiss, H.; Lindner, J.; Fassbender, J.
Abstract: The influence of ion induced magnetic patterning on the anisotropic magnetoresistance (AMR) is investigated in the first part. The AMR directly depends on the angle between the applied current and the magnetization of the material. To investigate this relationship a Kerr microscope for visualizing the magnetic domains is combined with magneto-transport measurements. The investigated samples are magnetic hybrid structures from irradiated and non-irradiated permalloy.

In the second part ion implantation is used to create spin wave channels. Fe60Al40films in the B2 phase is paramagnetic. Starting from a FeAl film in the paramagnetic state the incident ions randomize the site occupancies and, thereby, transform it to the chemically disordered, ferromagnetic A2 phase. Spin waves, the eigen-excitations of ferromagnets, are promising candidates for spin transport in lateral devices. The aim is to investigate spin wave propagation in this ferromagnetic material in free standing structure as well as in structure within a paramagnetic matrix.
  • Lecture (others)
    Hard Condensed Matter Theory Seminar, 24.01.2017, Mainz, Deutschland
Registration No. 25021 - Permalink

P1413 - Verfahren zur Metallisierung von Kunststoffteilen sowie Lösung
Hofinger, J.; Roos, S.; Günther, T.; Maffert, A.
Abstract: Die Erfindung umfasst ein Verfahren zur Metallisierung von Kunststoffteilen mit den Schritten Vorbehandlung der Kunststoffoberfläche, chemische Metallisierung, wobei zur Vorbehandlung, die Oberfläche des Kunststoffteiles mit mindestens einer niedrig siedenden organischen Flüssigkeit angelöst und/oder angequollen wird, sodass anschließend die angelöste und/oder angequollene Kunststoffoberfläche durch Verdampfen der mindestens einen niedrig siedenden organischen Flüssigkeit strukturiert wird und sodass die so strukturierte Oberfläche ohne Chromsäure-Schwefelsäure-Lösung hydrophiliert wird.
  • Patent
    DE102015201562 - Offenlegung: 04.08.2016, Nachanmeldungen: WO
Registration No. 25020 - Permalink

P1412 - Pockelszellen-Treiberschaltung mit Induktivitäten
Bergmann, T.; Siebold, M.; Löser, M.
Abstract: Die Treiberschaltung enthält eine erste Leitung, welche mit einem ersten Anschluss der Pockelszelle (18; CP) zu verbinden ist, und eine zweite Leitung, welche mit einem zweiten Anschluss der Pockelszelle (18; CP) zu verbinden ist, wobei die erste Leitung und/oder die zweite Leitung eine Induktivität 10 (14, 15; 24, 25) aufweist.
  • Patent
    EP3023832 - Offenlegung: 25.05.2016, Nachanmeldungen: US
Registration No. 25017 - Permalink

Micro reactor experiments on the partial isobutane oxidation as a multiphase process.
Willms, T.; Kryk, H.; Hampel, U.
Abstract: Tertiary butyl hydroperoxide (TBHP), as an intermediate for the production of propylene oxide according to the Oxirane process, is currently produced at industrial scale by the partial oxidation of liquid isobutane using bubble columns or bubble tray reactors. In this process, liquid isobutane reacts with oxygen at temperatures of 120 to 140 °C and pressures of 25 to 37 bar at high residence times of up to 12 hours. The conversion is limited to 35 to 50 % in order to obtain a TBHP selectivity of 50 to 60 % minimizing the formation of by-products, which are caused by the decomposition of the TBHP due to the complex reaction mechanism. Besides safety aspects, the high reaction enthalpy of the oxidation as well as heat and mass transport problems are further issues of this process. In the frame of the Helmholtz-Energy-Alliance project “Energy efficient chemical multiphase processes“, this reaction is investigated for the first time as a Taylor-Flow process in a broad range of flow rates, temperatures and pressures in a micro reactor with the aim to enhance the space-time yield of the process. The advantage of micro reactors are the high surface – volume ratio for an efficient heat transfer, the related, improved – nearly inherent – safety and the resulting possibility to investigate yet unexplored process windows for instance within the explosive region of a reaction mixture. A number of levers for the process intensification have been identified. In addition to the parameter ranges studied so far, higher pressures of up to 100 bar and uninvestigated initiator types, especially e.g hydrogen peroxide and high oxidation concentrations (50 to 100%) are applied, which have not been studied yet. Also, the influence of process parameters on the start-up time is investigated. Finally, the reaction medium characteristics of the isobutane – oxidant flow is modified by adding additives to the liquid phase or inert gases to the gas phase. For all parameters, the selecti¬vity and conversion of the reaction is studied. Therefore, the reaction course is followed by sampling and analyzing the reaction by GC/MS and GC–TCD where analytical methods have been developed to detect a maximum of by-products and intermediates. In the frame of the presentation, the results of preliminary investigations and the first multiphase flow oxidation experiments are given and discussed with respect to the reaction characteristics.
Keywords: isobutane oxidation, microreactor, t-butyl hydroperoxide, two phase process
  • Poster
    10th European Congress of Chemical Engineering, 3rd European Congress of Applied Biotechnology, 5th European Process Intensification Conference ECCE10+ECAB3+EPIC5, 27.09.-01.10.2015, Nice, France
  • Contribution to proceedings
    10th European Congress of Chemical Engineering, 3rd European Congress of Applied Biotechnology, 5th European Process Intensification Conference ECCE10+ECAB3+EPIC5, 27.09.-01.10.2015, Nice, France
Registration No. 25016 - Permalink

Fabrication of sub-50 nm silicon nanowires using inductively coupled plasma etching
Khan, M. B.; Deb, D.; Georgiev, Y. M.; Erbe, A.
Abstract: Development of an etching process for fabrication of ultrathin silicon nanowires (SiNWs) with inductively coupled plasma (ICP) source and C4F8/SF6 mixed gas recipe at 18 oC is reported. Etch selectivity of silicon (SOI) to hydrogen silsesquioxane (HSQ), a negative tone electron beam resist and selectivity of silicon (SOI) to SiO2 are investigated to identify suitable process window. Effects of ICP power, RF power, chamber pressure, flow rates and ratio of C4F8/SF6 on etch rate, selectivity and surface roughness are examined. Atomic force microscopy (AFM) is used for identifying surface roughness of the plain silicon (SOI) substrates after etching. Thereafter etching of HSQ patterned substrates is performed. Scanning electron microscopy is performed to observe the etch profile. Parameters such as flow rates of C4F8/SF6 are optimized to attain sub-50 nm SiNWs with smooth and vertical sidewalls.
  • Poster
    DPG Regensburg, 06.-11.03.2016, Regensburg, Germany
Registration No. 25015 - Permalink

Ge-doped GaSb thin films with zero mass density change upon crystallization for applications in phase change memories
Putero, M.; Coulet, M. V.; Muller, C.; Baehtz, C.; Raoux, S.; Cheng, H. Y.
Abstract: In order to optimize materials for phase change random access memories (PCRAM), the effect of Ge doping on Ga-Sb alloy crystallization was studied using combined in situ synchrotron x-ray techniques, electrical measurements, and static laser testing. The present data emphasize that the crystallization temperature can be increased up to 390C with subsequent higher thermal stability of the amorphous phase; phase segregation is evidenced with GaSb, Sb, and Ge phases that crystallize in a two-step crystallization process. The Ge-doped GaSb films exhibit a larger electrical contrast as compared to undoped GaSb alloy (up to 100). The optical contrast measured by laser testing is shown to follow the mass density change variations upon crystallization, with a negative contrast (higher value in amorphous state) whatever Ge-doping levels. In situ x-ray reflectivity measurements show that zero mass density change can be achieved by low Ge-doping. Ge-doped GaSb alloys look promising since a phase change material with zero mass density change and higher crystallization temperature satisfactorily fulfills the specifications for reliable PCRAM cells in terms of endurance and data retention.
Keywords: phase change memories; thin films Registration No. 25014 - Permalink

In Situ Observations of Phase Transitions in Metastable Nickel (Carbide)/Carbon Nanocomposites
Bayer, B. C.; Bosworth, D. A.; Michaelis, F. B.; Blume, R.; Habler, G.; Abart, R.; Weatherup, R. S.; Kidambi, P. R.; Baumberg, J. J.; Knop-Gericke, A.; Schloegl, R.; Baehtz, C.; Barber, Z. H.; Meyer, J. C.; Hofmann, S.
Abstract: Nanocomposite thin films comprised of metastable metal carbides in a carbon matrix have a wide variety of applications ranging from hard coatings to magnetics and energy storage and conversion. While their deposition using nonequilibrium techniques is established, the understanding of the dynamic evolution of such metastable nanocomposites under thermal equilibrium conditions at elevated temperatures during processing and during device operation remains limited. Here, we investigate sputterdeposited nanocomposites of metastable nickel carbide (Ni3C) nanocrystals in an amorphous carbon (a-C) matrix during thermal postdeposition processing via complementary in situ X-ray diffractometry, in situ Raman spectroscopy, and in situ Xray photoelectron spectroscopy. At low annealing temperatures (300 °C) we observe isothermal Ni3C decomposition into face-centered-cubic Ni and amorphous carbon, however, without changes to the initial finely structured nanocomposite morphology. Only for higher temperatures (400−800 °C) Ni-catalyzed isothermal graphitization of the amorphous carbon matrix sets in, which we link to bulk-diffusion-mediated phase separation of the nanocomposite into coarser Ni and graphite grains. Upon natural cooling, only minimal precipitation of additional carbon from the Ni is observed, showing that even for highly carbon saturated systems precipitation upon cooling can be kinetically quenched. Our findings demonstrate that phase transformations of the filler and morphology modifications of the nanocomposite can be decoupled, which is advantageous from a manufacturing perspective. Our in situ study also identifies the high carbon content of the Ni filler crystallites at all stages of processing as the key hallmark feature of such metal−carbon nanocomposites that governs their entire thermal evolution. In a wider context, we also discuss our findings with regard to the much debated potential role of metastable Ni3C as a catalyst phase in graphene and carbon nanotube growth.
Keywords: nickel carbide, carbon nano tubes; in-situ xray diffraction Registration No. 25013 - Permalink

Controlling Catalyst Bulk Reservoir Effects for Monolayer Hexagonal Boron Nitride CVD
Caneva, S.; Weatherup, R. S.; Bayer, B. C.; Blume, R.; Cabrero-Vilatela, A.; Braeuninger-Weimer, P.; Martin, M. B.; Wang, R.; Baehtz, C.; Schloegl, R.; Meyer, J. C.; Hofmann, S.
Abstract: Highly controlled Fe-catalyzed growth of monolayer hexagonal boron nitride (h-BN) films is demonstrated by the dissolution of nitrogen into the catalyst bulk via NH3 exposure prior to the actual growth step. This “pre-filling” of the catalyst bulk reservoir allows us to control and limit the uptake of B and N species during borazine exposure and thereby to control the incubation time and h-BN growth kinetics while also limiting the contribution of uncontrolled precipitation-driven h-BN growth during cooling. Using in situ X-ray diffraction and in situ X-ray photoelectron spectroscopy combined with systematic growth calibrations, we develop an understanding and framework for engineering the catalyst bulk reservoir to optimize the growth process, which is also relevant to other 2D materials and their heterostructures.
Keywords: hexagonal boron nitride (h-BN), chemical vapor deposition (CVD), borazine (HBNH)3, Registration No. 25012 - Permalink

Microstructure and strain relaxation in thin nanocrystalline platinumfilms produced via different sputtering techniques
Gruber, W.; Baehtz, C.; Horisberger, M.; Ratschinski, I.; Schmidt, H.
Abstract: In this study we investigated the correlation between microstructure and residual strain relaxation innanocrystalline Pt films with a thickness of about 20 nm produced by different deposition techniques:magnetron sputtering and ion beam sputtering. X-ray diffractometry was carried out using synchrotronradiation. The out-of-plane interplanar distance was measured during isothermal in situ annealing attemperatures between 130◦C und 210◦C. The thermoelastic expansion coefficient is equal for both types of nanocrystalline Pt films and slightly lower than for coarse grained Pt. The relaxation of residual out-of-plain strain depends on temperature and is significantly stronger in the case of the magnetron sputteredfilms than for the ion beam sputtered films. Different relaxation of compressive stress is ascribed tothe different microstructures which evolve during deposition via the corresponding deposition tech-nique. Thickness fringes around the (1 1 1) Bragg peak deposited via magnetron sputtering reveal thatthese films are essentially composed of columnar (1 1 1) oriented grains which cover the whole filmthickness. In contrast, no thickness fringes are observed around the (1 1 1) Bragg peak of films preparedby ion beam sputtering indicating a significantly different microstructure. This is confirmed by ElectronBackscatter Diffraction which reveals a (1 1 1) texture for both types of films. The (1 1 1) texture, however,is significantly stronger in the case of the magnetron sputtered films. Grain growth at low homologoustemperatures is considered to be an important contribution to relaxation of residual stress.
Keywords: microstructure sputtering diffraction Registration No. 25011 - Permalink

Microstructure of multilayer heterosystems containing molecules of Ge quantum dots in Si on the stages of nucleation and growth as revealed by EXAFS spectroscopy
Erenburg, S. B.; Trubina, S. V.; Zvereva, V. V.; Zinov’Ev, V. A.; Dvurechenskiy, A. V.; Kuchinskaya, P. A.; Kvashnina, K. O.
Abstract: GeK edge EXAFS (Extended X-Ray Absorption Fine Structure) spectra have been measured for multilayer semiconducting heterosystems containing interacted groups of quantum dots (“molecules from quantum dots”) ordered in rings on different stages of their growth depending on topologic parameters and growth conditions. In accordance with our results obtained previously for the quantum dots of SiGe, for the molecules of quantum dots it was found that deformation at the interface leads to decrease in the interatomic distance of Ge–Ge by ~0.03 Å. Effect of heterosystem topology and temperature at different stages of their growth on interlayer diffusion was investigated. It was found that at the first growth stage (growth of “seeded islands” serving as a basis for obtaining the molecules) at 700°C a concentration of Ge atoms in the system is ~38%. With further growth of the vertically-matched quantum dots groups the concentration of Ge increases up to ~43-47% depending on the growth conditions. Comparable analysis of different modes of EXAFS measurements was performed to determine precisely structural parameters of heterosystem SiGe with different thickness grown on Si(100) surface.
Keywords: microstructure, semiconductor heterosystem, molecules of quantum dots GeSi, EXAFS spectra Registration No. 25009 - Permalink

P1410 - Elektromagnet zur Führung von Teilchenstrahlen zur Strahlentherapie
Schürer, M.; Karsch, L.; Pawelke, J.; Zschetzsche, J.; Kroll, F.
Abstract: Die Erfindung betrifft Elektromagnete zur Führung von Teilchenstrahlen zur Strahlentherapie mit einer Spule in Verbindung mit einer elektrischen Energiequelle zur Ausbildung eines magnetischen Feldes. Die Elektromagnete zeichnen sich insbesondere dadurch aus, dass die Führung der Teilchenstrahlen mit einem gepulsten Magnetfeld erfolgt. Dazu besteht die Spule aus mindestens einem aus einem elektrisch nichtleitenden Material bestehenden Grundkörper mit wenigstens einem elektrischen und flexiblen Leiter mit mindestens einer Biegung. Weiterhin ist die Spule mit einer eine gepulste Energie liefernden Energiequelle verbunden. Die Spule besteht damit im Wesentlichen aus dem elektrischen Leiter und dem Grundkörper, wobei der Grundkörper ausschließlich als Träger fungiert. Der Grundkörper besitzt damit keine elektrischen Eigenschaften.
  • Patent
    DE102015200213 - Offenlegung: 14.07.2016
Registration No. 25008 - Permalink

Electrical characterization of two-dimensional materials and their heterostructures
Arora, H.; Seifert, G.; Cuniberti, G.; Helm, M.; Erbe, A.
Abstract: Two-dimensional (2D) materials have gained enormous attention in recent years owing to their excellent transport properties and mechanical flexibility. Several 2D materials like graphene, MoS2, h-BN are under intense study in the areas of electronics, optics and sensing. Apart from these materials, 2D polymers are also rapidly gaining attention due to easy tuning of their properties by altering their synthesis parameters. Polymers and inorganics together, allow us to develop 2D nanostructures whose electrical properties can be controlled. Thus, in this project, we aim to investigate novel 2D materials followed by their structural and electrical characterizations w.r.t transistor properties. Another focus will be to fabricate vertical heterostructures by stacking different 2D materials together and investigate resulting functionalities of the stack.
Keywords: Two-dimensional (2D) materials, 2D polymers, nanostructures, heterostructures
  • Contribution to proceedings
    2016 Radio and Antenna Days of the Indian Ocean (RADIO), 10.-13.10.2016, Reunion Island, France
    IEEE Xplore Digital Library: IEEE, 978-1-5090-2580-0
    DOI-Link: http://dx.doi.org/10.1109/RADIO.2016.7772014
  • Lecture (Conference)
    2016 Radio and Antenna Days of the Indian Ocean (RADIO), 10.-13.10.2016, Reunion Island, France
  • Poster
    Tailor-made 2D-materials and functional devices, 27.06.-01.07.2016, Bremen, Germany
  • Poster
    IHRS NanoNet International Workshop 2016, 30.08.-02.09.2016, Prague, Czech Republic
Registration No. 25007 - Permalink

Towards an Electronic Model for Reconfigurable Transistors
Fuchs, F.; Schuster, J.; Gemming, S.
Abstract: In contrast to conventional CMOS transistors, reconfigurable field effect transistors (RFETs) can be switched between n- and p-type behavior, which allows more compact and flexible circuit designs [1, 2]. Symmetry between n- and p-current is required and this can be achieved by strain engineering as experimentally demonstrated in Ref. [2]. However, a detailed understanding of the electron transport across the strained interface is not yet available and requires electronic models to capture all relevant transport mechanism.
We investigate the relation between strain and electron transport properties of planar interfaces between metallic NiSi 2 and semiconducting Si in <110> crystal orientation. We apply the non-equilibrium Green’s functions formalism together with density functional theory as implemented in Atomistix ToolKit [3] to calculate the transmission spectra. Using a modified version of the Landauer formula, we than obtain an expression for the current through the RFET and hence, the transfer characteristic can be investigated. A comparison between the calculated transfer characteristic using this model and experimental reference data [2] are performed. A very good agreement can be seen which verifies our model. However, in the experiment, the RFET was compressed during the oxidation process. Because the structure in the simulation was supposed to be unstrained, some pre-strain might be present in the simulation. We also study how strain, either applied perpendicular or parallel to the transport direction, alters the current. It can be seen that a small amount of strain is sufficient to change the ratio between n- and p-current and that symmetry can be achieved. Considering the above-mentioned pre-strain in the simulation, the general trend is also in agreement with experimental studies [1, 2].

[1] A. Heinzig et al., Reconfigurable Silicon Nanowire Transistors. Nano Letters 12, 119 (2012)
[2] A. Heinzig et al., Dually Active Silicon Nanowire Transistors and Circuits with Equal Electron and Hole Transport. Nano Letters 13, 4176 (2013)
[3] Atomistix ToolKit 15, QuantumWise A/S (www.quantumwise.com)

Keywords: reconfigurable transistor, silicon, density functional theory, non-equilibrium Green's function formalism, strain
  • Poster
    NanoNet International Workshop 2016, 30.08.-02.09.2016, Praha, Česká republika
Registration No. 25004 - Permalink

Businesskontept für die Wirtschaftlichkeitsprüfung einer Haldensanierung der Tiefenbachhalde in Altenberg
Scholz, A.
Abstract: Die vorliegende Masterarbeit beschäftigt sich mit dem Thema eines "Businesskonzepts für die Wirtschaftlichkeitsprüfung einer Haldensanierung der Tiefenbachhalde in Altenberg".
Es geht um die Frage, ob ein Re-mining, sprich eine Haldensanierung der Tiefenbachhalde mit Rohstoffrückgewinnung, wirtschaftlich durchgeführt werden und sich selbst finanzieren kann. Um die Wirtschaftlichkeit des Vorhabens überprüfen zu können, wurden alle schon vorhandenen Daten der möglichen Erlöse und der anfallenden Kosten recherchiert und zusammengetragen. Bei noch fehlenden Daten sollten Möglichkeiten zur Informationsbeschaffung aufgezeigt werden. Im Laufe der Arbeit hat sich gezeigt, dass genügend Daten für eine Wirtschaftlichkeitsbetrachtung vorhanden sind. Somit konnten im Anschluss daran verschiedene Szenarien bearbeitet werden. Das Ergebnis ist eine Gegenüberstellung der Erlöse zu den Kosten, wobei die Kosten um den Faktor 2,29 höher sind als die Erlöse. Auch bei den betrachteten Szenarien sind die Kosten jeweils höher als die Erlöse. Um eine Wirtschaftlichkeit erreichen zu können, müsste der Zinnpreis sehr stark ansteigen. Insgesamt sind die Ergebnisse kritisch zu beurteilen, da Annahmen das Ergebnis beeinflussen und die Aufbereitung auf einem Prozess von 1982 basiert.

Feasibility study to remediate the Tiefenbachhalde in Altenberg The Tiefenbachhalde Altenberg is a tailing of a former tin mine in the Erzgebirge. An extensive exploration conducted by researchers from HIF and TUBAF showed that the dump still contains about 8000 tons of valuable tin. However there are also about 4000 tons of arsenic, which could be an environmental hazard, if the tailing is treated improperly.
The idea is to remediate the dump and cover the costs by Re-mining of the tin. In this master thesis the economic feasibility of this concept is evaluated by a feasibility calculation.

Keywords: Wirtschaftlichkeitsprüfung, Haldensanierung, Re-mining / feasibility calculation, dump remediation, re-mining
  • Master thesis
    TU Bergakademie Freiberg, 2016
    Mentor: Prof. Dr. Michael Höck, Prof. Dr. Karl Gerald van den Boogaart
    0105 Seiten
Registration No. 25003 - Permalink

3D-geologische Modellierung der Nb-Ta-P-(LREE-) Lagerstätte Epembe, Namibia
Unger, G.
Abstract: Das aus den vorhandenen Daten erstellte Modell der Nb-Ta-P-(LREE)-Lagerstätte Epembe in Nordwest-Namibia, beinhaltet die Störungssysteme, sowie flexible 3D-Stratigraphische Grids (SGrids) der Sektoren B und K. Das Modell lässt Aussagen über die räumlichen Beziehungen zwischen Anreicherungszonen und Störungen im Untergrund zu. Die im Untersuchungsgebiet vorkommenden Lithologien wurden in Lithoeinheiten zusammengefasst und mit den geochemischen Daten verglichen. Dabei stellte sich heraus, dass die Anreicherungszonen der Elemente nicht mit den anstehenden Lithoeinheiten korrelieren. Des Weiteren ergaben sich lineare Zusammenhänge der Elemente U-Ta, U-Nb, Ta-Nb, HREE-LREE aus den geochemischen Daten der Bohrungen. Dies unterstreicht eine Intrusion von Magmen, die mit inkompatiblen Elementen angereichert waren. Die linearen Zusammenhänge der Elemente, spiegeln sich in den gleichen Anreicherungszonen der SGrids wieder. Die Korrelationen mit Uran werden im Modell nicht bestätigt, aufgrund der aufsummierten Darstellung der Gehalte von Uran, Thorium und Kalium. Eine weitere Ausnahme bilden die Anreicherungszonen von HREE-LREE im Sektor B. Da die Gehalte der schweren Seltenen Erden in den Anreicherungszonen der leichten Erden sehr gering sind. Diese Zonen wurden wahrscheinlich hydrothermal überprägt und es kam zur Auslaugung der HREE. Mit dem Modell konnte eine störungsgebundene Anreicherung von inkompatiblen Elementen (HFSE) nachgewiesen werden.
Mithilfe des Modells können Thesen der Genese der Lagerstätte aufgestellt werden:
1) Bei der Intrusion (vor 1215 MA) von gabbroiden, syenitischen Magmen in den Epupa Komplex, bildete sich der Karbonatit Dyke aus. Die Magmen waren vermutlich mit inkompatiblen Elementen angereichert.
2) Infolge der tektonischer Überprägung des Epembe Karbonatit Syenit Komplexes wurden diese Elemente wahrscheinlich durch hydrothermale Prozesse aus dem Umgebungsgestein gelaugt und kristallisierten dann entlang von Störungen aus. Dabei bildeten sich die modellierten Anreicherungszonen der Lagerstätte.
3) Die Auslaugung bildete Anreicherungszonen von Elementen, aber auch Zonen mit extrem geringen Elementgehalten (HREE). Da einige Elemente mobiler sind als andere.
4) Tektonische Strukturen spielten bei der Genese der Lagerstätte eine zentrale Rolle für Aufstiegs- und Platznahmemöglichkeiten von alkalischen oder karbonatischen Magmen und assoziierten REE-reichen Fluiden.
Die vorliegende Arbeit unterstreicht den Fakt, dass Seltene Erden Lagerstätten nicht ausschließlich durch magmatische Prozesse entstehen, sondern auch in Kombination mit hydrothermalen Prozessen. Des Weiteren wurde bewiesen das zur Genese von REE Lagerstätten, tektonische Strukturen eine entscheidende Rolle spielen.
  • Bachelor thesis
    Helmholtz-Zentrum Dresden-Rossendorf, Helmholtz Institut Freiberg, 2015
    Mentor: Dr. Richard Gloaguen
    46 Seiten
Registration No. 25002 - Permalink

Hyperspectral remote sensing for mineral mapping of structural related mineralizations around Mount Isa, Queensland, Australia
Jakob, S.
Abstract: The present report demonstrates the possibilities and limitations of remote sens- ing, especially hyperspectral data, for mineral mapping purposes, using the example of the Mount Isa Inlier. This geological area is situated in Northern Queensland, Australia, and is known for its considerable ore deposits and consequent mining of predominantly copper, zinc, lead, silver and gold. Beside hyperspectral HyMap data, multispectral Landsat 8 and SRTM digital elevation data were analyzed. A three-week field study supported the investigations by data delivered from rock sampling and field spectral measurements. The observations were concentrated on four study areas and four main objectives: the location of orebodies near Mount Isa mine by mapping their altered outcrops, the targeting of critical elements at the Mary Kathleen U-REE deposit, the investigation of the dependency between the shear and fault-controlled vein-copper deposits of Mount Isa inlier and main deep-crustal faults and the testing of a fixed-wing drone for 3D-photogrammetry of geological features.
Throughout the study, mineral mapping using remote sensing data, especially hyperspectral data, turned out to deliver high qualitative results when it is supported by additional infor- mation. In situ investigation of the observed mineralizations for validation is important and can deliver such data, for instance by the investigation of rock samples or spectral measure- ments. Since mineralizations and alterations are often related to structures, their analysis and consideration can provide crucial hints. Without additional data it is very difficult up to impossible to create and interpret mineral mapping results accurately. The most significant result throughout the study was the determination of a new site of gossanous, silicified ridges south of the Mount Isa mining complex. They coincide with the outcrops of mineralized parts of the Urquhart Shale, which form the mined Pb-Zn-Ag deposits and are probably related to structures. Their occurrence was validated through fieldwork observations including rock sampling and spectral measurements. The gathered information additionally supported the mapping of those ridges using HyMap data, which confirmed the connection between the north-south trending ridges and the Mount Isa mine deposits.
  • Master thesis
    Helmholtz-Zentrum Dresden-Rossendorf, Helmholtz Institut Freiberg, 2014
    Mentor: Dr. Richard Gloaguen
    75 Seiten
Registration No. 25001 - Permalink

Hyperspectral remote sensing of carbonatite hosted REE-deposits in Namibia
Zimmermann, R.ORC
Abstract: In this thesis, two case-studies for exploration of carbonatite hosted REE-deposits in Namibia using hyperspectral remote sensing data are presented. REEs have enormous economic importance because they are the major constituents of high-tech electronic devices and are non-substitutable.
The two areas of interest in Namibia are Epembe/Kunene region and Lofdal/Bergville Farm close to Khorixas. Namibia is convenient because of less vegetation, a good data coverage, and a good geological knowledge.
Multi- and hyperspectral data of multiple source and scale in combination with tectonic geomorphology were used for data analysis. In a first step, spectral signatures and geomorphic indices were extracted, followed by expert classification made by a Decision Tree approach. The detailed processing chain is shown in figure 1.
Standard procedures for spectral unmixing (e.g. Spectral Feature Fitting, Matched Filtering) are well suited to map the abundances of carbonate minerals. However, calcretes, meta-sedimentary units, and amphibolites have similar spectral signatures in the SWIR range and are difficult to distinguish.
More advantageous approaches, like Self-Organizing maps and Decision Trees, were used to discriminate the carbonatite from surrounding rocks with similar signatures. The carbonatites are associated to specific textural, geomorphic and structural patterns. Incorporating these features into hyperspectral data analysis improve classification results and reduce misclassifications for carbonatite.
  • Master thesis
    Helmholtz-Zentrum Dresden-Rossendorf, Helmholtz Institut Freiberg, 2014
    Mentor: Dr. Richard Gloaguen
    67 Seiten
Registration No. 25000 - Permalink

Exploration mit Drohnen
Gloaguen, R.
Abstract: Am Helmholtz-Institut Freiberg für Ressourcentechnologie entwickeln wir neue Methoden zur Erkundung mineralischer Rohstoffe mittels Drohnen. Unser Hexacopter transportiert beispielsweise eine hyperspektrale Kamera, die uns die Kartierung von Schlüsselmineralen erlaubt und so mögliche Lagerstätten identifizieren lässt. Einsätze in Namibia, Grönland und Spanien haben diese Erwartungen bestätigt.
  • Invited lecture (Conferences)
    Future Technologies - Innovationen aus den Technikwissenschaften, 26.01.2017, Dresden, Deutschland
Registration No. 24999 - Permalink

Novel Nanoelectronic Devices and Technologies for Their Fabrication
Georgiev, Y.ORC
Abstract: The traditional scaling of microelectronic devices was over in 2003 (130 nm node). New “performance boosters” are being used since then: (i) strained silicon (Si) since 2004 (90 nm node), (ii) high-k gate dielectrics + metal gates (HKMG) instead of SiO2 + poly-Si gates since 2008 (45 nm node) and (iii) non-planar 3D (tri-gate) transistor architecture since 2012 (22 nm node). Further improvements are expected by the implementation of (i) new device architectures, (ii) high-mobility channel materials such as silicon-germanium (SiGe), Ge, III-Vs, carbon nanotubes (CNTs), graphene and/or other 2D materials, etc., (iii) new (non-digital) functionalities (e.g. sensing), usually referred to as “More than Moore”, and (iv) new computational principals such as spintronics, quantum computing, etc.

In this talk I will present three novel nanoelectronics devices that have been proposed and demonstrated for the first time in the last 5-6 years: (i) junctionless nanowire transistors (JNTs) [1], (ii) 3D vertically stacked nanowire field effect transistors (VSNFETs) [2] and (iii) reconfigurable field effect transistors (RFETs) [3]. These devices embody to some extent the first three of the above-mentioned future “performance boosters”: (i) they have advanced transistor architecture, (ii) JNTs have been fabricated not only in Si but also in Ge as a high-mobility channel material and (iii) JNTs and VSNFETs have been implemented as chemical and biosensors demonstrating excellent sensing performance.
I will briefly discuss the specifics in the functioning of those devices, outlining their advantages and disadvantages. I will then consider the technologies for their fabrication and the challenges that they are facing. Finally, I will present examples of the devices fabricated for some particular applications, showing results of their structural and electrical characterisation. In the case of JNTs and VSNFETs I will focus mostly on their application as chemo/biosensors [4-8]. Additionally, I will also show the first Ge-based JNTs [9]. In the case of RFETs I will present the recent results of top-down fabrication and characterisation of such devices on silicon-on-insulator (SOI) wafers.

[1] J.P. Colinge, C.-W. Lee, A. Afzalian, N.D. Akhavan, R. Yan, I. Ferain, P. Razavi, B. O’Neill, A. Blake, M. White, A.-M. Kelleher, B. McCarthy and R. Murphy, Nanowire transistors without junctions. Nat. Nanotechnol. 5 (2010) 225.
[2] E. Buitrago, M. Fernández-Bolaños, A.M. Ionescu, Vertically stacked Si nano-structures for biosensing applications, Microelectron. Eng. 97 (2012) 345–348.
[3] A. Heinzig, T. Mikolajick, J. Trommer, D. Grimm and W. M. Weber, Nano Lett. 13 (2013) 4176-4181.
[4] Y. M. Georgiev, N. Petkov, B. McCarthy, R. Yu, V. Djara, D. O'Connell, O. Lotty, A. M. Nightingale, N. Thamsumet, J. C. deMello, A. Blake, S. Das, J. D. Holmes. Fully CMOS-compatible top-down fabrication of sub-50 nm silicon nanowire sensing devices. Microelectron. Eng. 118 (2014) pp. 47-53.
[5] Y. M. Georgiev, R. Yu, N. Petkov, O. Lotty, A. M. Nightingale, J. C. deMello, R. Duffy, J. D. Holmes. Silicon and Germanium Junctionless Nanowire Transistors for Sensing and Digital Electronics Applications. In "Functional Nanomaterials and Devices for Electronics, Sensors and Energy Harvesting.", A. Nazarov, F. Balestra, V. Kilchytska, D. Flandre eds. Springer International Publishing AG, Cham, Switzerland, 2014, pp. 367-388.
[6] E. Buitrago, G. Fagas, M. Fernández-Bolanos Badia, Y.M. Georgiev, M. Berthomé, A.M. Ionescu. Junctionless silicon nanowire transistors for the tunable operation of a highly sensitive, low power sensor. Sens. Actuators B 183 (2013) 1– 10.
[7] E. Buitrago, M. Fernández-Bolaños, Y. M. Georgiev, R. Yu, O. Lotty, J. D. Holmes, A. M. Nightingale, H. M. Guerin, A. M. Ionescu. Electrical Characterization of High Performance, Liquid Gated Vertically Stacked SiNW-Based 3D FET for Biosensing Applications. Sens. Actuators B 199 (2014) pp. 291-300.
  • Invited lecture (Conferences)
    IEEE 25th International Scientific Conference Electronics - ET2016, 12.-14.09.2016, Sozopol, Bulgaria
Registration No. 24997 - Permalink

High Resolution Nanofabrication
Georgiev, Y.ORC
Abstract: The aim of nanofabrication is to create structures and devices with minimum dimensions lower than 100 nm. There are two main nanofabrication approaches, bottom-up and top-down. In the former, the structures and devices are created from small to large in an additive fashion, which relies to a great extent on self-organisation processes. In the latter, the fabrication goes from large to small where nanostructures and devices are carved from a larger piece of material in a subtractive fashion. It is much more mature than the bottom-up approach and is based on two long-established processes: (i) nanolithography, where a stencil with the required pattern is created in a sacrificial layer called “resist”, deposited on the main working material, and (ii) pattern transfer through the resist stencil into the base material.

In the present paper we will present results on high-resolution nanofabrication of structures and devices with critical dimensions (CD) below 10 nm on silicon (Si), silicon-on-insulator (SOI), germanium (Ge) and germanium-on-insulator (GeOI) substrates. The fabrication was mainly within the frames of the top-down approach and was based on electron beam lithography (EBL) with positive and negative resists followed by a pattern transfer with both additive (metal deposition and lift-off) and subtractive (dry etching) methods. Moreover, high-end results on combination of bottom-up and top-down approaches will also be presented such as (i) contacting of bottom-up grown and randomly distributed nanostructures and fabrication of devices out of them as well as (ii) pattern density multiplication by directed self assembly (DSA) of block-copolymers (BCP). We believe that these results are showing some of the promising trends for future development of high-resolution nanofabrication.
  • Lecture (Conference)
    12th International Conference "Electron Beam Technologies" (EBT 2016), 13.-18.06.2016, Varna, Bulgaria
Registration No. 24996 - Permalink

Top-down fabrication of silicon nanowires
Georgiev, Y.ORC
Abstract: Results on top-down fabrication of silicon (Si) nanowires (Ws) towards junctionless nanowire transistors, Si NW-based biosensors and reconfigurable field effect transistors have been presented at the SENTECH "Plasma Process Technology” seminar.
  • Invited lecture (Conferences)
    SENTECH "Plasma Process Technology” seminar, 07.04.2016, Berlin, Deutschland
Registration No. 24995 - Permalink

Ultrahigh Sensitivity Chemical and Biological Sensors Based on Silicon Junctionless Nanowire Transistors
Georgiev, Y.ORC; Yu, R.; Buitrago, E.; Nightingale, A. M.; Lotty, O.; Petkov, N.; Holmes, J. D.
Abstract: Junctionless nanowire transistors (JNTs) are very promising as chemo- biosensors due to their simple structure, easy fabrication and potential for ultrahigh sensitivity. Therefore, JNT sensors with various numbers, lengths, and widths (down to 10 nm) of the nanowires were fabricated by a top-down process on positively doped SOI wafers. The nanowires were functionalised either with 3-aminopropyltriethoxysilane (APTES) or with APTES and biotin. Polydimethylsiloxane (PDMS) stamps with microfluidic channels were then attached to the chip surface and buffer solutions containing different analytes were flowed over the sensors by a syringe pump. In this way, series of experiments for sensing ionic strength, pH value, and the protein streptavidin were performed. The JNT sensors demonstrated the highest sensitivity reported to date towards streptavidin, corresponding to a detection of only few protein molecules.
  • Lecture (Conference)
    80. Jahrestagung der DPG und DPG-Frühjahrstagung, 06.-11.03.2016, Regensbur, Deutschland
Registration No. 24993 - Permalink

Tunneling Magnetoresistance with Zero-moment Half-metallic electrodes
Borisov, K.; Betto, D.; Lau, Y. C.; Fowley, C.; Titova, A.; Thiyagarajah, N.; Atcheson, G.; Lindner, J.; Deac, A. M.; Coey, M.; Stamenov, P.; Rode, K.
Abstract: In recent years, great attention has been paid to the research of intermetallic Heusler compounds. These materials have widely tuneable properties. They display high spin polarisation , low magnetic moment , low Gilbert damping α and high effective magnetic anisotropy field. All of the above-mentioned characteristics play key role at the choice of materials for integration in spin-transfer-torque oscillators. Here we have successfully integrated a compensated half-metallic ferrimagnet as a fixed layer in magnetic tunnel junctions (MTJ). Theoretically this class of materials was predicted in 1995 by van Leuken and de Groot, but experimentally the zero-moment half-metal was realised only in 2014 for a near-cubic Heusler alloy of Mn, Ru and Ga (MRG). Here, MTJs with different insertion layers between MRG and the tunnel barrier were studied. Sufficient tunnelling magnetoresistance (TMR) ratios were demonstrated for Mn2RuGa / Al 0.6 nm / MgO / CoFeB MTJs. We measured the switching properties of MTJ as a function of applied bias voltage and ex-situ annealing temperature. At low bias (U ≈ 10mV), the as-grown sample shows TMR ratio ≈ 1.6% at room-temperature, annealing at 375°C leads to increasing of TMR to ≈ 7.5%. At higher negative bias (U ≈ - 0.5 V), the TMR varies from -2.9 to -6.3%, for the as-grown sample and the sample annealed at 375°C, respectively. Low temperature measurements on the same device show in excess of 40% TMR close to zero bias. Moreover, we demonstrate non-zero TMR while cooling through the compensation temperature (when the magnetic moment is zero). Finally, by changing the electrode composition from Mn2Ru0.65 Ga through to Mn2Ru1.1Ga we also demonstrate finite TMR at ambient temperature with an electrode designed to be compensated at room temperature.
Keywords: Magnetic Tunnel Junctions Heusler Alloy Ferrimagnetism Half-metal
  • Lecture (Conference)
    61st Annual Conference on Magnetism and Magnetic Materials, 31.10.-04.11.2016, New Orleans, Louisiana, United States of America
Registration No. 24990 - Permalink

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