Immunophenotyping and oncogene amplifications in tumors of the papilla of Vater

Carcinomas of the ampulla of Vater are rare and assumed to generally arise from preexisting adenomas (adenoma-carcinoma sequence). Histologically, distinct subtypes can be distinguished that were shown to differ significantly in terms of clinical outcome. Since pathologists usually receive bioptic tissue samples of ampullary tumors obtained during endoscopy, accurate classification of carcinoma subtypes can sometimes be difficult on morphological criteria alone. We therefore performed immunohistochemistry using a panel of established marker proteins (CK7, CK20, p21, p27, ESA, bax, and ephrin-B2) on 175 carcinoma, 111 adenoma, and 152 normal mucosa specimens of the ampulla of Vater and identified distinct immunoprofiles for every carcinoma subtype. Fluorescence in situ hybridization analyses of therapeutic target genes (c-myc, EGFR1, CCND1, HER2) found CCND1 to represent the most frequently amplified gene in our series (7.5%

Cell entry of a host-targeting protein of oomycetes requires gp96

The animal-pathogenic oomycete Saprolegnia parasitica causes serious losses in aquaculture by infecting and killing freshwater fish. Like plant-pathogenic oomycetes, S. parasitica employs similar infection structures and secretes effector proteins that translocate into host cells to manipulate the host. Here, we show that the host-targeting protein SpHtp3 enters fish cells in a pathogen-independent manner. This uptake process is guided by a gp96-like receptor and can be inhibited by supramolecular tweezers. The C-terminus of SpHtp3 (containing the amino acid sequence YKARK), and not the N-terminal RxLR motif, is responsible for the uptake into host cells. Following translocation, SpHtp3 is released from vesicles into the cytoplasm by another host-targeting protein where it degrades nucleic acids. The effector translocation mechanism described here, is potentially also relevant for other pathogen-host interactions as gp96 is found in both animals and plants.This work is supported by the [European Community’s] Seventh Framework Programme [FP7/2007–2013] under grant agreement no. [238550] (L.L., J.D.-U., C.J.S., P.v.W.); BBSRC [BBE007120/1, BB/J018333/1 and BB/G012075/1] (F.T., I.d.B., C.J.S., S.W., P.v.W.); Newton Global Partnership Award [BB/N005058/1] (F.T., P.v.W.), the University of Aberdeen (A.D.T., T.R., C.J.S., P.v.W.) and Deutsche Forschungsgemeinschaft [CRC1093] (P.B., T.S.). We would like to acknowledge the Ministry of Higher Education Malaysia for funding INA. We would like to thank Brian Haas for his bioinformatics support. We would like to acknowledge Neil Gow and Johannes van den Boom for critical reading of the manuscript. We would like to acknowledge Svetlana Rezinciuc for technical help with pH-studies

A high-gradient test of a 30 GHz copper accelerating structure

The CLIC study is investigating a number of different materials at different frequencies in order to find ways to increase achievable accelerating gradient and to understand what are the important parameters for high-gradient operation. So far a series of rf tests have been made with a set of identical-geometry 30 GHz and X-band structures in copper, tungsten and molybdenum. A new test of a 30 GHz copper accelerating structure has been completed in CTF3 with pulse lengths up to 70 ns. The new results are presented and compared to the previous structures to determine dependencies of quantities such accelerating gradient, material, frequency, pulse length, conditioning rate, breakdown rate and surface damage

A High-Gradient Test of a 30 GHz Molybdenum-Iris Structure

The CLIC study is actively investigating a number of different materials in an effort to find ways to increase achievable accelerating gradient. So far a series of rf tests have been made with a set of identical-geometry structures: a W-iris 30 GHz structure, a Mo-iris 30 GHz structure (with pulses as long as 16 ns) and a scaled Mo-iris X-band structure. A second Mo-iris 30 GHz structure of the same geometry has now been tested in CTF3 with pulse lengths up to 350 ns. The structure was conditioned to a gradient of 140 MV/m with a 70 ns pulse length and a breakdown rate slope of 13 MV/m per decade has been measure

CLIC: a Two-Beam Multi-TeV e±e\pm Linear Collider

The CLIC study of a high-energy (0.5 - 5 TeV), high-luminosity (1034 - 1035 cm-2 sec-1) e+e- linear collider is presented. Beam acceleration using high frequency (30 GHz) normal-conducting structures operating at high accelerating fields (150 MV/m) significantly reduces the length and, in consequence, the cost of the linac. Using parameters derived from general scaling laws for linear colliders, the beam stability is shown to be similar to lower frequency designs in spite of the strong wake-field dependency on frequency. A new cost-effective and efficient drive beam generation scheme for RF power production by the so-called "Two-Beam Acceleration" method is described. It uses a thermionic gun and a fully-loaded normal-conducting linac operating at low frequency (937 MHz) to generate and accelerate the drive beam bunches, and RF multiplication by funnelling in compressor rings to produce the desired bunch structure. Recent 30 GHz hardware developments and CLIC Test Facility (CTF) results are described

Flaws in the perfect bubble

Perfect bubbles like that surrounding the galactic HII region RCW 120 (Deharveng et al. 2009) have been interpreted as proof of concept for the collect and collapse (C & C) mechanism of triggered star formation. The cold, dusty clumps surrounding RCW 120 are aligned along an almost spherical shell. It has been inferred that these massive clumps, which sometimes harbour young stellar objects, have been formed via the fragmentation of the dense, swept-up shell. In order to better understand the triggering mechanisms at work in shells like RCW 120, we perform high-resolution, three dimensional SPH simulations of HII regions expanding into fractal molecular clouds. In a second step, we use RADMC-3D to compute the synthetic dust continuum emission from our simulations, in order to compare them with observations of RCW 120 made with APEX-LABOCA at 870 micron. We show that a distribution of clumps similar to the one seen in RCW 120 can readily be explained by a non-uniform underlying molecular cloud structure. Hence, a shell-like clump configuration around an HII region does not necessarily support the C & C scenario, but rather reflects the pre-existing, non-uniform density distribution of the molecular cloud into which the HII region expands