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Background Viscum album L. (Santalaceae), commonly known as mistletoe, is a hemiparasitic plant traditionally used in complementary cancer treatment. Its antitumor potential is mostly attributed to the presence of aqueous soluble metabolites; however, the use of ethanol as solvent also permits the extraction of pharmacological compounds with antitumor potential. The clinical efficacy of mistletoe therapy inspired the present work, which focuses on ethanolic extracts (V. album “mother tinctures”, MT) prepared from different host trees. Methods Samples from three European subspecies (album, austriacum, and abietis) were harvested, and five different V. album-MT strains were prepared. The following phytochemical analyses were performed: thin layer chromatography (TLC), high-performance liquid chromatography (HPLC) and liquid chromatography-high resolution mass spectrometry (LC-HRMS). The proliferation assay was performed with WST-1 after incubation of tumor (Yoshida and Molt-4) and fibroblast cell lines (NIH/3 T3) with different MT concentrations (0.5 to 0.05% v/v). The cell death mechanism was investigated by flow cytometry (FACS) using Annexin V-7AAD. Results Chemical analyses of MT showed the presence of phenolic acids, flavonoids and lignans. The MT flavonoid and viscotoxin contents (mg/g fresh weight) were highest in Quercus robur (9.67 ± 0.85 mg/g) and Malus domestica (3.95 ± 0.58 mg/mg), respectively. The viscotoxin isoform proportions (% total) were also different among the VA subspecies with a higher content of A3 in V. album growing on Abies alba (60.57 ± 2.13). The phytochemical compounds as well as the viscotoxin contents are probably related to the antitumor effects of MT. The cell death mechanisms evaluated by colorimetric and FACS methodologies involved necrotic damage, which was host tree-, time- and dose- dependent, with different selectivity to tumor cells. Mother tincture from V. album ssp. abietis was the most effective at inducing in vitro cellular effects, even when incubated at the smallest concentration tested, probably because of the higher content of VT A3. Conclusion Our results indicate the promising antitumor potential of Viscum album ethanolic extracts and the importance of botanical and phytochemical characterization for in vitro anti-proliferative effects.

In the upgrade of the Belle detector at KEK (Tsukuba, Japan) the two innermost layers of the vertex detector will be realized by a pixel detector (PXD) consisting of DEPFET (DEpleted P-channel Field Effect Transistor) matrices. As the position of the detector will be very close to the beam pipe, it will suffer from intense radiation levels. The main radiation background is the luminosity related 4-fermion final state radiation, which damages the silicon bulk material and the silicon dioxide from the gate contacts. With the dose expected at Belle II, the DEPFET suffers mainly from additional leakage current and increase in noise. In addition, defects in the silicon dioxide change transistor parameters, e.g. the threshold voltage. We will show results on the hardness factor of electrons after a 10 MeV electron irradiation which was performed in the dose and energy range relevant for the PXD. In addition, we present X-ray irradiations of DEPFET equivalent test structures and compare radiation hardness for different oxide parameters in the prototype production.

X-ray free-electron lasers provide unique opportunities for exploring ultrafast dynamics and for imaging the structures of complex systems. Understanding the response of individual atoms to intense X-rays is essential for most free-electron laser applications. First experiments have shown that, for light atoms, the dominant interaction mechanism is ionization by sequential electron ejection, where the highest charge state produced is defined by the last ionic state that can be ionized with one photon. Here, we report an unprecedentedly high degree of ionization of xenon atoms by 1.5 keV free-electron laser pulses to charge states with ionization energies far exceeding the photon energy. Comparing ion charge-state distributions and fluorescence spectra with state-of-the-art calculations, we find that these surprisingly high charge states are created via excitation of transient resonances in highly charged ions, and predict resonance enhanced absorption to be a general phenomenon in the interaction of intense X-rays with systems containing high-Z constituents. Researchers create high ionization states, up to Xe36+, using 1.5 keV free-electron laser pulses. The higher than expected ionization may be due to transient resonance-enhanced absorption and the effect may play an important role in interactions of intense X-rays with high-Z elements and radiation damage.

To expand the detection efficiency Silicon Drift Detectors (SDDs) with various customized radiation entrance windows, optimized detector areas and geometries have been developed. Optimum values for energy resolution, peak to background ratio (P/B) and high count rate capability support the development. Detailed results on sensors optimized for light element detection down to Boron or even lower will be reported. New developments for detecting medium and high X-ray energies by increasing the effective detector thickness will be presented. Gamma-ray detectors consisting of a SDD coupled to scintillators like CsI(Tl) and LaBr3(Ce) have been examined. Results of the energy resolution for the 137Cs 662 keV line and the light yield (LY) of such detector systems will be reported.

Physical review letters 108, 5 (2012). doi:10.1103/PhysRevLett.108.245005, Published by APS, College Park, Md.

Distinct expression patterns of keratins reflect different epithelial prototypes and different epithelial differentiation pathways. In order to get evidence of the expression of keratins in a hormone-dependent tissue in man, we investigated 70 epithelial tissue specimens by means of SDS-gel electrophoresis and immunoblot. Every tissue probe belonged to different generation phases such as sexual maturity, climacteric and postmenopausal period and pregnancy. Keratins 1(avb), 4(avb), 5(avb), 10(avb), 13, 14 were detected regularly whereas keratins 6, 16, and 19 are expressed irregularly. During all generation phases, with the exception of pregnancy, the keratins 1 and 10, associated with the epidermal differentiation, and keratins 4 and 13, associated with the differentiation to a non-keratinizing stratified epithelium, are synthesized simultaneously. However in pregnancy, i.e. pregnancy at term of delivery, only K4/K13 are expressed, while K1/K10 are below the detection limit. In terms of keratin expression vaginal epithelium represents a mosaic of differentiation. Only in pregnancy the 'pure' type of a nonkeratinizing epithelium is seen, apparently as a result of the high concentration of estrogens.

Minimization of the total detector capacitance due the small area readout node on one hand and to the integration of the front-end FET directly onto the detector (see Fig. 1a) on the other hand, combined with an ultra-low leakage current process makes the SDD with integrated FET an excellent energy resolving device with measured energy resolution down to 123 eV for Mn-Kα line at moderate temperatures (easily reached with Peltier cooling, e.g. -20°C) and very short shaping times 0.5 to 1 μs. These are performance values which can not be achieved by any other EDS detector.

The need of high quality spectroscopic semiconductor imaging detectors in X-ray astronomy was the principal driving force in founding the MPI Semiconductor Laboratory. Detectors developed in this laboratory are based on new function principles and are processed in the silicon detector processing line established within the laboratory. We describe the development of pnCCDs as already used in the XMM-Newton European X-ray observatory and foreseen for eROSITA, the DEPFET based pixel detector for XEUS and a new development which makes it possible to measure charge with a precision below one elementary charge. A noise value of 0.25 electron r.m.s. has already been reached.

The high resolution three-dimensional structure of the newly discovered plant viscotoxin C1, from the Asiatic Viscum album ssp. Coloratum ohwi, has been determined in solution by (1)H NMR spectroscopy at pH 3.6 and 285 K. The viscotoxin C1-fold, consisting of a helix-turn-helix motif and a short stretch of an antiparralel beta-sheet is very similar to that found for the highly similar viscotoxins A2 and A3 and for other related thionins. Different functional properties of members of the thionin family are discussed here in light of the structural and electrostatic properties. Among the very homologous family of alpha- and beta-thionins, known for their antimicrobial activity, the viscotoxin subfamily differs from the other members because of its high toxicity against tumoral cells. Key residues for the modulation of viscotoxin cytotoxicity have been identified on the basis of sequence and structural alignment.

Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7–August 11, 2011.

Extended abstract of a paper presented at Microscopy and Microanalysis 2010 in Portland, Oregon, USA, August 1 – August 5, 2010.

The high-resolution three-dimensional structure of the plant toxin viscotoxin A3, from Viscum album L., has been determined in solution by (1)H NMR spectroscopy at pH 3.6 and 12 degrees C (the structure has been deposited in the Protein Data Bank under the id. code 1ED0). Experimentally derived restraints including 734 interproton distances from nuclear Overhauser effect measurements, 22 hydrogen bonds, 32 φ angle restraints from J coupling measurements, together with three disulphide bridge constraints were used as input in restrained molecular dynamics, followed by minimization, using DYANA and Discover. Backbone and heavy atom root-mean-square deviations were 0.47+/-0.11 A (1 A=10(-10) m) and 0.85+/-0.13 A respectively. Viscotoxin A3 consists of two alpha-helices connected by a turn and a short stretch of antiparallel beta-sheet. This fold is similar to that found in other thionins, such as crambin, hordothionin-alpha and -beta, phoratoxin A and purothionin-alpha and -beta. The difference in the observed biological activity for thionins of known structure is discussed in terms of the differences in the calculated surface potential distribution, playing an important role in their function through disruption of cell membranes. In addition, the possible role in DNA binding of the helix-turn-helix motif of viscotoxin A3 is discussed.

This study documents a strong and statistically significant association between the use of the glycopeptide avoparcin as a growth promoter in Norwegian poultry production and the occurrence of vancomycin-resistant Enterococcus species (VRE). Avoparcin was approved as a feed additive for broilers and turkeys in Norway in 1986 and was banned from June 1, 1995. In a survey conducted in Norway between June, 1995 and March, 1997, VRE were isolated from fecal samples from 106 out of 109 poultry houses previously exposed to avoparcin (97%) and from six out of 33 poultry houses never exposed to avoparcin (18%) (RR = 5.35). Samples from previously exposed poultry houses were collected in three time periods. The proportion of positive samples remained high (96-98%), in all three time periods indicating a persistence of vancomycin resistance among enterococci for more than a year and a half after the withdrawal of avoparcin. VRE were also isolated from six out of 10 poultry farmers living on farms previously exposed to avoparcin, and from none of 16 farmers living on farms never exposed to avoparcin. Moreover, VRE were isolated from 68 out of the 225 broiler carcasses investigated (30%). The resistance to vancomycin was a high-level type (MIC > or = 256 microg/ml) mediated by the vanA gene. For comparison, VRE could only be isolated from two out of 147 fecal samples from Norwegian flocks of swine (1%). Because avoparcin never has been used in Norwegian swine production, this observation strengthens the association between the use of avoparcin in animal husbandry and the occurrence of VRE.

Extended abstract of a paper presented at Microscopy and Microanalysis 2008 in Albuquerque, New Mexico, USA, August 3 – August 7, 2008

Extended abstract of a paper presented at Microscopy and Microanalysis 2008 in Albuquerque, New Mexico, USA, August 3 – August 7, 2008

Extended abstract of a paper presented at Microscopy and Microanalysis 2006 in Chicago, Illinois, USA, July 30 – August 3, 2006

Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.

Human vaginal epithelium provides a good model to study hormonally regulated differentiation. Differentiation in this tissue can be characterized by the expression of the keratins 1 and 13 which represent the epidermal and nonkeratinizing pathway in stratified epithelia, respectively. In the present study immunohistochemistry was applied on sections of vaginal epithelium derived from women at various stages of the menstrual cycle or during pregnancy. Our results demonstrate that both pathways are realized simultaneously during sexual maturity and that the maximum for synthesis of keratins 1 and 13 is seen during the first half of the cycle. In contrast keratin 1 is not detectable at the end of pregnancy, thus reflecting a completely suppressed epidermal differentiation. As the levels of the female sex hormones, i.e. estrogens, is significantly increased in pregnant women over that in nonpregnant women, these results suggest a possible role of estrogens in downregulating the epidermal differentiation pathway.

The semiconductor laboratory of the Max-Planck-Institutes for physics and for extraterrestrial physics develops and fabricates silicon sensors for scientific experiments in astronomy and highenergy physics, as well as for industrial applications. Among them are state-of-the-art detectors for X-ray imaging and spectroscopy. Their common features are the integration of the readout electronics on the detector chip and a fully depleted bulk with a non-structured thin entrance window, guaranteeing excellent energy resolution and high quantum efficiency over a wide energy range. Fully depleted and backside illuminated Charge Coupled Devices (pn-CCDs) have been developed and are operated successfully as focal plane detector of the XMM-Newton satellite. They have a sensitive area of 6 x 6 cm≤ with a pixel size of 150 x 150 µm≤, an equivalent noise charge of 4 el. rms. operating at 150 K, and an ultra-fast full frame readout time of 4.5 msec. The integrated detector-preamplifier structure DEPFET (DEpleted P-channel Field Effect Transistor) is the basic element of an Active Pixel Sensor (APS) with random accessible pixels, flexible readout modes, and the potential for repetitive non-destructive readout with subelectron resolution. Spectroscopy measurements of single DEPFET structures demonstrate an unequalled electronic noise of 2.2 el. rms at room temperature.

Background: The mistletoe Viscum album L. (Santalaceae) is a semi-parasitic plant that grows on different host trees. Although V. album antitumor activity is mainly associated with aqueous preparations, recently we showed antitumoral effects of homeopathic V. album tinctures containing also the ethanolic soluble compounds [1]. Aims: to analyze the phytochemical profile of different Viscum album homeopathic tinctures as well as their in vitro effects in tumoral cells. Methodology: The Viscum album samples (leaves, stems and berries) were collected in 2016 and 2017 (summer), and in 2018 (winter) at different locations in Switzerland. After harvest, they were immediately submitted to ethanolic extraction (45% V/V) using homeopathic methodology [2, 3]. The following mother tinctures (MT) were prepared: V. album ssp. album growing on Malus domestica, Quercus sp. and Ulmus sp., V. album ssp. austriacum from Pinus sylvestris, and V. album ssp. abietis from Abies alba. The homeopathic dynamizations (1-3dH; 6, 12, 30dH) were prepared with the respective MT. The phytochemical profiles were analysed by High Performance Liquid Chromatography tandem Mass Spectroscopy, HPLC and Thin Layer Chromatography. MT prepared in 2016 were also submitted to the Pfeiffer’s circular chromatography (PCC) [4]. The proliferation assay was performed by WST-1 [5] after incubation of tumoral cells (Yoshida and Molt-4) with non-dynamized (0.5 to 0.05% v/v) and dynamized MT. Apoptosis/necrosis was measured by flow cytometer (FACS) using Annexin V-FITC [5], and the cellular morphological aspects were analysed by light microscope. Results and Discussion: The chemical analyses of MT identified the presence of phenolic acids, flavonoids, lignans, as principal compounds. Besides, the HPLC indicated higher viscotoxin concentration in the summer harvest of Abies alba, Malus domestica and Quercus (897, 475, 219 ?g/mL), respectively. The PCC methodology permitted the MT differentiation. The higher levels of cellular mortality were attribute to Abies alba, Malus domestica and Quercus (p