Post-test simulations for the NACIE-UP benchmark by STH codes

This paper illustrates the results obtained in the last phase of the NACIE-UP benchmark activity foreseen inside the EU SESAME Project. The purpose of this research activity, performed by system thermal–hydraulic (STH) codes, is finalized to the improvement, development and validation of existing STH codes for Heavy Liquid Metal (HLM) systems. All the participants improved their modelling of the NACIE-UP facility, respect to the initial blind simulation phase, adopting the actual experimental boundary conditions and reducing as much as possible sources of uncertainty in their numerical model. Four different STH codes were employed by the participants to the benchmark to model the NACIE-UP facility, namely: CATHARE for ENEA, ATHLET for GRS, RELAP5-3D© for the “Sapienza” University of Rome and RELAP5/Mod3.3(modified) for the University of Pisa. Three reference tests foreseen in the NACIE-UP benchmark and carried out at ENEA Brasimone Research Centre were analysed from four participants. The data from the post-test analyses, performed independently by the participant using different STH codes, were compared together and with the available experimental results and critically discussed

Inhibition of cell migration and invasion mediated by the TAT-RasGAP317-326 peptide requires the DLC1 tumor suppressor.

TAT-RasGAP317-326, a peptide corresponding to the 317-326 sequence of p120 RasGAP coupled with a cell-permeable TAT-derived peptide, sensitizes the death response of various tumor cells to several anticancer treatments. We now report that this peptide is also able to increase cell adherence, prevent cell migration and inhibit matrix invasion. This is accompanied by a marked modification of the actin cytoskeleton and focal adhesion redistribution. Interestingly, integrins and the small Rho GTP-binding protein, which are well-characterized proteins modulating actin fibers, adhesion and migration, do not appear to be required for the pro-adhesive properties of TAT-RasGAP317-326. In contrast, deleted in liver cancer-1, a tumor suppressor protein, the expression of which is often deregulated in cancer cells, was found to be required for TAT-RasGAP317-326 to promote cell adherence and inhibit migration. These results show that TAT-RasGAP317-326, besides its ability to favor tumor cell death, hampers cell migration and invasion

Empirical comparison of high gradient achievement for different metals in DC and pulsed mode

For the SwissFEL project, an advanced high gradient low emittance gun is under development. Reliable operation with an electric field, preferably above 125 MV/m at a 4 mm gap, in the presence of an UV laser beam, has to be achieved in a diode configuration in order to minimize the emittance dilution due to space charge effects. In the first phase, a DC breakdown test stand was used to test different metals with different preparation methods at voltages up to 100 kV. In addition high gradient stability tests were also carried out over several days in order to prove reliable spark-free operation with a minimum dark current. In the second phase, electrodes with selected materials were installed in the 250 ns FWHM, 500 kV electron gun and tested for high gradient breakdown and for quantum efficiency using an ultra-violet laser.Comment: 25 pages, 13 figures, 5 tables. Follow up from FEL 2008 conference (Geyongju Korea 2008) New Title in JVST A (2010) : Vacuum breakdown limit and quantum efficiency obtained for various technical metals using DC and pulsed voltage source

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: A phase 1 dose-escalation study

BackgroundThis phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody-liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer.MethodsPatients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) q3w; MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) and cyclophosphamide (450 mg/m2) q3w.ResultsSixty-nine patients were treated. The most common adverse events (AEs) were fatigue and nausea. Grade 3/4 AEs of special interest included neutropenia, fatigue, mucosal inflammation, anemia, thrombocytopenia, febrile neutropenia, and palmar-plantar erythrodysesthesia. The MTD was not reached. With MM-302 ≥ 30 mg/m2, overall response rate (ORR) was 13% and median progression-free survival (mPFS) 7.4 months (95% CI: 3·5-10·9) in all arms. In 25 anthracycline-naïve patients, ORR was 28·0% and mPFS 10·9 months (95% CI: 1·8-15·3). Imaging with 64Cu-labeled MM-302 visualized tumor-drug penetrance in tumors throughout the body, including the brain.ConclusionMM-302 monotherapy, in combination with trastuzumab, or trastuzumab plus cyclophosphamide, was well tolerated and showed promising efficacy. The selected phase 2 MM-302 dose was 30 mg/m2 plus 6 mg/kg trastuzumab q3w

Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis

Background. Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. Aim:To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. Patients: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. Methods: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. Results: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (< 2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. Conclusion: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance. Copyright (c) 2006 S. Karger AG, Basel

Beta-decay of nuclei around Se-90. Search for signatures of a N=56 sub-shell closure relevant the r-process

Nuclear structure plays a significant role on the rapid neutron capture process (r-process) since shapes evolve with the emergence of shells and sub-shells. There was some indication in neighboring nuclei that we might find examples of a new N=56 sub-shell, which may give rise to a doubly magic Se-90 nucleus. Beta-decay half lives of nuclei around Se-90 have been measured to determine if this nucleus has in fact a doubly-magic character. The fragmentation of Xe-136 beam at the National Superconducting Cyclotron Laboratory at Michigan State University was used to create a cocktail of nuclei in the A=90 region. We have measured the half lives of twenty-two nuclei near the r-process path in the A=90 region. The half lives of As-88 and Se-90 have been measured for the first time. The values were compared with theoretical predictions in the search for nuclear-deformation signatures of a N=56 sub-shell, and its possible role in the emergence of a potential doubly-magic Se-90. The impact of such hypothesis on the synthesis of heavy nuclei, particularly in the production of Sr, Y and Zr elements was investigated with a weak r-process network. The new half lives agree with results obtained from a standard global QRPA model used in r-process calculations, indicating that Se-90 has a quadrupole shape incompatible with a closed N=56 sub-shell in this region. The impact of the measured Se-90 half-life in comparison with a former theoretical predication associated with a spherical half-life on the weak-r-process is shown to be strong

Evaluation of pre-analytical factors affecting plasma DNA analysis.

Pre-analytical factors can significantly affect circulating cell-free DNA (cfDNA) analysis. However, there are few robust methods to rapidly assess sample quality and the impact of pre-analytical processing. To address this gap and to evaluate effects of DNA extraction methods and blood collection tubes on cfDNA yield and fragment size, we developed a multiplexed droplet digital PCR (ddPCR) assay with 5 short and 4 long amplicons targeting single copy genomic loci. Using this assay, we compared 7 cfDNA extraction kits and found cfDNA yield and fragment size vary significantly. We also compared 3 blood collection protocols using plasma samples from 23 healthy volunteers (EDTA tubes processed within 1 hour and Cell-free DNA Blood Collection Tubes processed within 24 and 72 hours) and found no significant differences in cfDNA yield, fragment size and background noise between these protocols. In 219 clinical samples, cfDNA fragments were shorter in plasma samples processed immediately after venipuncture compared to archived samples, suggesting contribution of background DNA by lysed peripheral blood cells. In summary, we have described a multiplexed ddPCR assay to assess quality of cfDNA samples prior to downstream molecular analyses and we have evaluated potential sources of pre-analytical variation in cfDNA studies