Structural investigations of CeIrIn5{_5} and CeCoIn5{_5} on macroscopic and atomic length scales

For any thorough investigation of complex physical properties, as encountered in strongly correlated electron systems, not only single crystals of highest quality but also a detailed knowledge of the structural properties of the material are pivotal prerequisites. Here, we combine physical and chemical investigations on the prototypical heavy fermion superconductors CeIrIn${_5}$ and CeCoIn${_5}$ on atomic and macroscopic length scale to gain insight into their precise structural properties. Our approach spans from enhanced resolution X-ray diffraction experiments to atomic resolution by means of Scanning Tunneling Microscopy (STM) and reveal a certain type of local features (coexistence of minority and majority structural patterns) in the tetragonal HoCoGa$_5$-type structure of both compounds.Comment: 8 pages, 5 figures, submitted to JPSJ (SCES 2013

Schallemissionsmessungen zur Spanndrahtbrucherkennung

Die Schallemissionsanalyse zur Spanndrahtbrucherkennung etabliert sich in Deutschland als Verfahren zur Überwachung vorgespannter Konstruktionen. Das Interesse liegt dabei auf der zuverlässigen Erkennung von Spanndrahtbrüchen, also der Beschreibung des Quellmechanismus. Zwei Forschungsschwerpunkte gehen damit einher, die hier thematisiert und erste Ergebnisse vorgestellt werden: Einerseits gilt es die Kette von der Signalentstehung, Signalübertragung bis hin zur aufgezeichneten Welle allgemeingültig zu formulieren, um Rückschlüsse auf den Quellmechanismus zu ziehen. Andererseits werden maschinelle Lernverfahren angewendet, um das Potential solcher Methoden auf diese Art von Daten aufzuzeigen. Nach Berechnung von Merkmalen aus dem Frequenzraum konnte bei einer Klassifikation von Hammerschlag-Signalen eine Genauigkeit von 98% erreicht werden.Acoustic emission analysis for tendon wire break detection is establishing itself in Germany as a method for monitoring of prestressed structures. The focus lies in the reliable detection of tendon wire breaks, i.e. the description of the source mechanism. Two main areas of research are associated with this, whichare discussed in this paper: On the one hand, the measurement chain for describing the signal transmission from signal generation to the recorded wave must be formulated in a generally valid way in order to draw conclusions about the source mechanism. On the other hand, machine learning methods are used to show the potential of such methods for this kind of data. After calculating features from the frequency space, an accuracy of 98 % could be achieved with a classification

New histone deacetylase inhibitors as potential therapeutic tools for advanced prostate carcinoma

The anti-epileptic drug valproic acid is also under trial as an anti-cancer agent due to its histone deacetylase (HDAC) inhibitory properties. However, the effects of valproic acid (VPA) are limited and concentrations required for exerting anti-neoplastic effects in vitro may not be reached in tumour patients. In this study, we tested in vitro and in vivo effects of two VPA-derivatives (ACS2, ACS33) on pre-clinical prostate cancer models. PC3 and DU-145 prostate tumour cell lines were treated with various concentrations of ACS2 or ACS33 to perform in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and to evaluate tumour cell adhesion to endothelial cell monolayers. Analysis of acetylated histones H3 and H4 protein expression was performed by western blotting. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. Tumour sections were assessed by immunohistochemistry for histone H3 acetylation and proliferation. ACS2 and ACS33 significantly up-regulated histone H3 and H4 acetylation in prostate cancer cell lines. In micromolar concentrations both compounds exerted growth arrest in PC3 and DU-145 cells and prevented tumour cell attachment to endothelium. In vivo, ACS33 inhibited the growth of PC3 in subcutaneous xenografts. Immunohistochemistry and western blotting confirmed increased histone H3 acetylation and reduced proliferation. ACS2 and ACS33 represent novel VPA derivatives with superior anti-tumoural activities, compared to the mother compound. This investigation lends support to the clinical testing of ACS2 or ACS33 for the treatment of prostate cancer

L1-CAM expression in ccRCC correlates with shorter patients survival times and confers chemoresistance in renal cell carcinoma cells

Conflicting data exist about the expression of L1 cell adhesion molecule (L1-CAM) in clear cell renal cell carcinoma (ccRCC). To determine the clinical usefulness of L1-CAM as a therapeutic or prognostic marker molecule in renal cancer patients, we analyzed its expression on a cohort of 282 renal cell carcinoma (RCC) patients. L1-CAM expression was found in 49.5% of 282 renal cancer tissues. Importantly, L1-CAM expression in patients with ccRCC was associated with significantly shorter patient survival time. We further present evidence that L1-CAM was involved in the resistance against therapeutic reagents like rapamycin, sunitinib and cisplatin. The downregulation of L1-CAM expression decreased renal cancer cell proliferation and reduced the expression of cyclin D1. In addition, we found out that Von Hippel-Lindau (VHL) deficiency was accompanied by a downregulation of the transcription factor PAX8 and L1-CAM. In normal renal tissue, PAX8 and L1-CAM were co-expressed in collecting duct cells. Importantly, the downregulation of PAX8 by small interfering RNA increased the expression of L1-CAM and concomitantly induced the migration of renal cancer cells. Furthermore, we observed in 65.3% of 282 RCC patients a downregulation of PAX8 expression. With chromatin immunoprecipitation analysis, we additionally demonstrate that PAX8 can bind to the promoter of L1-CAM and we further observed that the downregulation of PAX8 was accompanied by increased L1-CAM expression in a high fraction of ccRCC patients. In summary, we show that VHL and PAX8 are involved in the regulation of L1-CAM in renal cancer and L1-CAM represents an important therapeutic and prognostic marker protein for the treatment of ccRC

The histone deacetylase inhibitor valproic acid alters growth properties of renal cell carcinoma in vitro and in vivo

Histone deacetylase (HDAC) inhibitors represent a promising class of antineoplastic agents which affect tumour growth, differentiation and invasion. The effects of the HDAC inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre-clinical renal cell carcinoma (RCC) models. Caki-1, KTC-26 or A498 cells were treated with various concentrations of VPA during in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and to evaluate cell cycle manipulation. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. The anti-tumoural potential of VPA combined with low-dosed interferon-α (IFN-α) was also investigated. VPA significantly and dose-dependently up-regulated histones H3 and H4 acetylation and caused growth arrest in RCC cells. VPA altered cell cycle regulating proteins, in particular CDK2, cyclin B, cyclin D3, p21 and Rb. In vivo, VPA significantly inhibited the growth of Caki-1 in subcutaneous xenografts, accompanied by a strong accumulation of p21 and bax in tissue specimens of VPA-treated animals. VPA–IFN-α combination markedly enhanced the effects of VPA monotherapy on RCC proliferation in vitro, but did not further enhance the anti-tumoural potential of VPA in vivo. VPA was found to have profound effects on RCC cell growth, lending support to the initiation of clinical testing of VPA for treating advanced RCC

Molecular targeting of prostate cancer cells by a triple drug combination down-regulates integrin driven adhesion processes, delays cell cycle progression and interferes with the cdk-cyclin axis

Background: Single drug use has not achieved satisfactory results in the treatment of prostate cancer, despite application of increasingly widespread targeted therapeutics. In the present study, the combined impact of the mammalian target of rapamycin (mTOR)-inhibitor RAD001, the dual EGFr and VGEFr tyrosine kinase inhibitor AEE788 and the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) on prostate cancer growth and adhesion in vitro was investigated. Methods: PC-3, DU-145 and LNCaP cells were treated with RAD001, AEE788 or VPA or with a RAD-AEE-VPA combination. Tumor cell growth, cell cycle progression and cell cycle regulating proteins were then investigated by MTT-assay, flow cytometry and western blotting, respectively. Furthermore, tumor cell adhesion to vascular endothelium or to immobilized extracellular matrix proteins as well as migratory properties of the cells was evaluated, and integrin alpha and beta subtypes were analyzed. Finally, effects of drug treatment on cell signaling pathways were determined. Results: All drugs, separately applied, reduced tumor cell adhesion, migration and growth. A much stronger anti-cancer effect was evoked by the triple drug combination. Particularly, cdk1, 2 and 4 and cyclin B were reduced, whereas p27 was elevated. In addition, simultaneous application of RAD001, AEE788 and VPA altered the membranous, cytoplasmic and gene expression pattern of various integrin alpha and beta subtypes, reduced integrin-linked kinase (ILK) and deactivated focal adhesion kinase (FAK). Signaling analysis revealed that EGFr and the downstream target Akt, as well as p70S6k was distinctly modified in the presence of the drug combination. Conclusions: Simultaneous targeting of several key proteins in prostate cancer cells provides an advantage over targeting a single pathway. Since strong anti-tumor properties became evident with respect to cell growth and adhesion dynamics, the triple drug combination might provide progress in the treatment of advanced prostate cancer

Experimental determination of the longitudinal pier stiffness of a long railway viaduct

Track–bridge interaction plays a decisive role in the design of long railway bridges due to the high braking and acceleration forces that occur and the fact that the continuous rail is attached to the superstructure. A fundamental parameter for the calculation of the effects of track–bridge interaction is the equivalent longitudinal stiffness of piers and abutments with fixed bearings. The equivalent horizontal stiffness is commonly calculated using a pile group model. The static and “dynamic” stiffnesses of the Itz valley railway viaduct were determined experimentally by using a static diagnostic load test and a braking test, which allowed for the verification of the additional rail stresses and the bearing forces with realistic input parameters. Furthermore, numerical 3D FE analyses of the deep foundation system were carried out to provide class-A predictions of the experimental results. In this article, the experimental setup and the execution and evaluation of the two tests are presented. A comparison of the experimental results and the numerical predictions is also carried out

New MTCA.4-based Hardware Developments for the Control of the Optical Synchronization Systems at DESY

The optical synchronization group at DESY is operating and continuously enhancing their laser-based synchronization systems for various facilities which need femtosecond-stable timing. These include the free-electron lasers FLASH and the upcoming European XFEL as well as the electron diffraction machine REGAE(Relativistic Electron Gun for Atomic Exploration) and the future plasma acceleration test facilities (LAO LA and FLASHforward). One of the major upgrades under development is the migration of the entire electronic control hardware to the new MTCA.4 platform which w as introduced as the new standard for accelerator control in many facilities worldwide. In this paper we present the applied modules and the topology of the new systems. Main advantages are a compact design with higher performance, redundancy, and remote management