Experiments with Very High Energy Synchrotron Radiation

The use of synchrotron radiation with very high photon energies has become possible only with the latest generation of storage rings. All high-electron-energy synchrotron sources will have a dedicated program for the use of very high photon energies. The high-energy beamline ID15 at the ESRF was the first beamline built and dedicated to this purpose, and it has now been in user operation for more than three years. The useful energy range of this beamline is 30-1000 keV and the superconducting insertion device for producing the highest attainable photon energies is described in detail. The techniques most often used today are diffraction and Compton scattering; an overview of the most important experiments is given. Both techniques have been used in the investigation of magnetic systems, and, additionally, the high resolution in reciprocal space, which can be achieved in diffraction, has led to a series of applications. Other fields of research are addressed, and attempts to indicate possible future research areas of high-energy synchrotron radiation are made

A hard x ray split and delay unit for the HED experiment at the European XFEL

For the High Energy Density HED experiment [1] at the European XFEL [2] an x ray split and delay unit SDU is built covering photon energies from 5 keV up to 20 keV [3]. This SDU will enable time resolved x ray pump x ray probe experiments [4,5] as well as sequential diffractive imaging [6] on a femtosecond to picosecond time scale. Further, direct measurements of the temporal coherence properties will be possible by making use of a linear autocorrelation [7,8]. The set up is based on geometric wavefront beam splitting, which has successfully been implemented at an autocorrelator at FLASH [9]. The x ray FEL pulses are split by a sharp edge of a silicon mirror coated with multilayers. Both partial beams will then pass variable delay lines. For different photon energies the angle of incidence onto the multilayer mirrors will be adjusted in order to match the Bragg condition. For a photon energy of h amp; 957; 20 keV a grazing angle of amp; 952; 0.57 has to be set, which results in a footprint of the beam 6 amp; 963; on the mirror of l 98 mm. At this photon energy the reflectance of a Mo B4C multi layer coating with a multilayer period of d 3.2 nm and N 200 layers amounts to R 0.92. In order to enhance the maximum transmission for photon energies of h amp; 957; 8 keV and below, a Ni B4C multilayer coating can be applied beside the Mo B4C coating for this spectral region. Because of the different incidence angles, the path lengths of the beams will differ as a function of wavelength. Hence, maximum delays between 2.5 ps at h amp; 957; 20 keV and up to 23 ps at h amp; 957; 5 keV will be possibl

Thomson Scattering Measurements of Plasma Dynamics

The authors propose to investigate the dynamics of plasmas in the warm dense matter (WDM) regime on ultra-short time scales. Accessible plasma conditions are in the density range of n = 10{sup 20} - 10{sup 23} cm{sup -3} and at moderate temperatures of T = 1 - 20 eV. These plasmas are of importance for laboratory astrophysics, high energy density science and inertial confinement fusion. They are characterized by a coupling parameter of {Lambda} {approx}> 1, where electromagnetic interactions are of the same order as the kinetic energy. The high density of the plasma makes it opaque to radiation in the visible range and, as a consequence, UV up to x-ray radiation can be used to probe such systems. Therefore a wide range in the temperature-density plane of WDM is presently unexplored and only the VUV-FEL opens for the first time the opportunity for its detailed investigation. In equilibrium, the macroscopic state of the plasma is completely characterized by its density and temperature. In pump-probe experiments however, the plasma is initially in a nonequilibrium state and relaxes towards equilibrium within the relaxation time {tau}{sub R}. For t > {tau}{sub R}, the plasma is in an equilibrium state and expands hydrodynamically on a time scale {tau}{sub H}. The proposed experiment measures the time-resolved Thomson scattering signal with the VUV-FEL radiation characterizing the plasma in equilibrium and nonequilibrium states. Both regimes are extremely interesting and will provide new insight into the following phenomena: (1) details of nonequilibrium correlations, (2) relaxation phenomena, (3) hydrodynamic expansion, (4) recombination kinetics. The time-resolved Thomson scattering signal is obtained in a pump-probe experiment by varying the delay between pump and probe. The final stage of the relaxation process (t {approx} {tau}{sub R}) is of special interest since the plasma components (electrons and ion species) can be assumed to be in quasi-equilibrium. This allows for accurate measurements of the electron temperature using the detailed balance relation. For times t {approx}< {tau}{sub R} the scattering spectrum provides also the plasmon damping in nonequilibrium from which information on the formation and decay of collective excitations at short time scales can be obtained. At large time scales (t {approx}> {tau}{sub H}) the hydrodynamic expansion of the plasma sets in. Detailed information on the evolution of the plasma in this regime is available from sophisticated hydrodynamic computer simulations which can be tested with the proposed measurements. With the decreasing plasma density due to the expansion, recombination processes become important and need to be considered as well

EFS shows biallelic methylation in uveal melanoma with poor prognosis as well as tissue-specific methylation

<p>Abstract</p> <p>Background</p> <p>Uveal melanoma (UM) is a rare eye tumor. There are two classes of UM, which can be discriminated by the chromosome 3 status or global mRNA expression profile. Metastatic progression is predominantly originated from class II tumors or from tumors showing loss of an entire chromosome 3 (monosomy 3). We performed detailed <it>EFS </it>(<it>embryonal Fyn-associated substrate</it>) methylation analyses in UM, cultured uveal melanocytes and normal tissues, to explore the role of the differentially methylated <it>EFS </it>promoter region CpG island in tumor classification and metastatic progression.</p> <p>Methods</p> <p><it>EFS </it>methylation was determined by direct sequencing of PCR products from bisulfite-treated DNA or by sequence analysis of individual cloned PCR products. The results were associated with clinical features of tumors and tumor-related death of patients.</p> <p>Results</p> <p>Analysis of 16 UM showed full methylation of the <it>EFS </it>CpG island in 8 (50%), no methylation in 5 (31%) and partial methylation in 3 (19%) tumors. Kaplan-Meier analysis revealed a higher risk of metastatic progression for tumors with <it>EFS </it>methylation (p = 0.02). This correlation was confirmed in an independent set of 24 randomly chosen tumors. Notably, only UM with <it>EFS </it>methylation gave rise to metastases. Real-time quantitative RT-PCR expression analysis revealed a significant inverse correlation of <it>EFS </it>mRNA expression with <it>EFS </it>methylation in UM. We further found that <it>EFS </it>methylation is tissue-specific with full methylation in peripheral blood cells, and no methylation in sperm, cultured primary fibroblasts and fetal muscle, kidney and brain. Adult brain samples, cultured melanocytes from the uveal tract, fetal liver and 3 of 4 buccal swab samples showed partial methylation. <it>EFS </it>methylation always affects both alleles in normal and tumor samples.</p> <p>Conclusions</p> <p>Biallelic <it>EFS </it>methylation is likely to be the result of a site-directed methylation mechanism. Based on partial methylation as observed in cultured melanocytes we hypothesize that there might be methylated and unmethylated precursor cells located in the uveal tract. The <it>EFS </it>methylation of a UM may depend on which type of precursor cell the tumor originated from.</p

Targets for high repetition rate laser facilities: Needs, challenges and perspectives

A number of laser facilities coming online all over the world promise the capability of high-power laser experiments with shot repetition rates between 1 and 10Ã\u82 Hz. Target availability and technical issues related to the interaction environment could become a bottleneck for the exploitation of such facilities. In this paper, we report on target needs for three different classes of experiments: Dynamic compression physics, electron transport and isochoric heating, and laser-driven particle and radiation sources. We also review some of the most challenging issues in target fabrication and high repetition rate operation. Finally, we discuss current target supply strategies and future perspectives to establish a sustainable target provision infrastructure for advanced laser facilities

Detection of micrometastasis by cytokeratin 20 RT-PCR is limited due to stable background transcription in granulocytes

The reverse transcription polymerase chain reaction (RT-PCR) amplification of cytokeratin 20 (CK20) mRNA is considered a promising candidate method for the detection of circulating tumour cells in bone marrow and peripheral blood of cancer patients. In this study we have investigated the diagnostic specificity of the CK20 mRNA detection in samples from healthy donors (HD; n = 33), intensive care units patients (ICU; n = 20) and bone marrow obtained from patients suffering from chronic inflammatory diseases (CID; n = 14). RNAs purified from stabilized lysates showed positive results in 24% of the HD group (8/33), 35% of the ICU group (8/20) and in 40% of the CID group (5/14). The use of Ficoll gradients to separate nucleated cells completely restored the specificity of this CK20 RT-PCR assay. The CK20-expressing cells are positively identified to belong to the granulocyte fraction of leucocytes, which appear to express the gene on a background level. Our results demonstrate for the first time that CK20 mRNA expression is not limited to epithelium. Its occurrence in normal granulocytes has to be considered in tests designed to detect circulating cancer cells or micrometastases. © 1999 Cancer Research Campaig

Does ocular treatment of uveal melanoma influence survival?

Treatment of uveal (intraocular) melanoma is aimed at prolonging life, if possible conserving the eye and useful vision. About 50% of patients develop fatal metastatic disease despite successful eradication of the primary intraocular tumour. The effect of ocular treatment on survival is unknown, because the same survival data from case series can be interpreted in different ways. Treatment is therefore based on intuition and varies greatly between centres. Randomised trials of treatment vs non-treatment of asymptomatic tumours are desirable but would be controversial, difficult, expensive and possibly inconclusive. Strategies for coping with uncertainty are needed to avoid unethical care

Small intestinal mucosa expression of putative chaperone fls485

<p>Abstract</p> <p>Background</p> <p>Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. <it>fls485 </it>coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze <it>fls48</it>5 expression in human small intestinal mucosa.</p> <p>Methods</p> <p><it>fls485 </it>expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several <it>in situ </it>techniques and usage of newly synthesized mouse monoclonal antibodies.</p> <p>Results</p> <p>fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c.</p> <p>Conclusions</p> <p>Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.</p