Measured Radiation and Background Levels During Transmission of Megawatt Electron Beams Through Millimeter Apertures

We report measurements of photon and neutron radiation levels observed while transmitting a 0.43 MW electron beam through millimeter-sized apertures and during beam-off, but accelerating gradient RF-on, operation. These measurements were conducted at the Free-Electron Laser (FEL) facility of the Jefferson National Accelerator Laboratory (JLab) using a 100 MeV electron beam from an energy-recovery linear accelerator. The beam was directed successively through 6 mm, 4 mm, and 2 mm diameter apertures of length 127 mm in aluminum at a maximum current of 4.3 mA (430 kW beam power). This study was conducted to characterize radiation levels for experiments that need to operate in this environment, such as the proposed DarkLight Experiment. We find that sustained transmission of a 430 kW continuous-wave (CW) beam through a 2 mm aperture is feasible with manageable beam-related backgrounds. We also find that during beam-off, RF-on operation, multipactoring inside the niobium cavities of the accelerator cryomodules is the primary source of ambient radiation when the machine is tuned for 130 MeV operation.Comment: 9 pages, 11 figures, submitted to Nuclear Instruments and Methods in Physics Research Section

Reliability of AlGaN/GaN high electron mobility transistors on low dislocation density bulk GaN substrate: Implications of surface step edges

To enable gaining insight into degradation mechanisms of AlGaN/GaN high electron mobility transistors, devices grown on a low-dislocation-density bulk-GaN substrate were studied. Gateleakage current and electroluminescence (EL) monitoring revealed a progressive appearance of EL spots during off-state stress which signify the generation of gate current leakage paths.Atomic force microscopy evidenced the formation of semiconductor surface pits at the failure location, which corresponds to the interaction region of the gate contact edge and the edges ofsurface steps

Thermodynamic properties of excess-oxygen-doped La2CuO4.11 near a simultaneous transition to superconductivity and long-range magnetic order

We have measured the specific heat and magnetization {\it versus} temperature in a single crystal sample of superconducting La$_{2}$CuO$_{4.11}$ and in a sample of the same material after removing the excess oxygen, in magnetic fields up to 15 T. Using the deoxygenated sample to subtract the phonon contribution, we find a broad peak in the specific heat, centered at 50 K. This excess specific heat is attributed to fluctuations of the Cu spins possibly enhanced by an interplay with the charge degrees of freedom, and appears to be independent of magnetic field, up to 15 T. Near the superconducting transition $T_{c}$($H$=0)= 43 K, we find a sharp feature that is strongly suppressed when the magnetic field is applied parallel to the crystallographic c-axis. A model for 3D vortex fluctuations is used to scale magnetization measured at several magnetic fields. When the magnetic field is applied perpendicular to the c-axis, the only observed effect is a slight shift in the superconducting transition temperature.Comment: 8 pages, 8 figure

Modelling neurofibromatosis type 1 tibial dysplasia and its treatment with lovastatin

<p>Abstract</p> <p>Background</p> <p>Bowing and/or pseudarthrosis of the tibia is a known severe complication of neurofibromatosis type 1 (NF1). Mice with conditionally inactivated neurofibromin (Nf1) in the developing limbs and cranium (Nf1Prx1) show bowing of the tibia caused by decreased bone mineralisation and increased bone vascularisation. However, in contrast to NF1 patients, spontaneous fractures do not occur in Nf1Prx1 mice probably due to the relatively low mechanical load. We studied bone healing in a cortical bone injury model in Nf1Prx1 mice as a model for NF1-associated bone disease. Taking advantage of this experimental model we explore effects of systemically applied lovastatin, a cholesterol-lowering drug, on the Nf1 deficient bone repair.</p> <p>Methods</p> <p>Cortical injury was induced bilaterally in the <it>tuberositas tibiae </it>in Nf1Prx1 mutant mice and littermate controls according to a method described previously. Paraffin as well as methacrylate sections were analysed from each animal. We divided 24 sex-matched mutant mice into a lovastatin-treated and an untreated group. The lovastatin-treated mice received 0.15 mg activated lovastatin by daily gavage. The bone repair process was analysed at three consecutive time points post injury, using histological methods, micro computed tomography measurements and <it>in situ </it>hybridisation. At each experimental time point, three lovastatin-treated mutant mice, three untreated mutant mice and three untreated control mice were analysed. The animal group humanely killed on day 14 post injury was expanded to six treated and six untreated mutant mice as well as six control mice.</p> <p>Results</p> <p>Bone injury repair is a complex process, which requires the concerted effort of numerous cell types. It is initiated by an inflammatory response, which stimulates fibroblasts from the surrounding connective tissue to proliferate and fill in the injury site with a provisional extracellular matrix. In parallel, mesenchymal progenitor cells from the periost are recruited into the injury site to become osteoblasts. In Nf1Prx1 mice bone repair is delayed and characterised by the excessive formation and the persistence of fibro-cartilaginous tissue and impaired extracellular matrix mineralisation. Correspondingly, expression of Runx2 is downregulated. High-dose systemic lovastatin treatment restores Runx2 expression and accelerates new bone formation, thus improving cortical bone repair in Nf1Prx1 tibia. The bone anabolic effects correlate with a reduction of the mitogen activated protein kinase pathway hyper-activation in Nf1-deficient cells.</p> <p>Conclusion</p> <p>Our data suggest the potential usefulness of lovastatin, a drug approved by the US Food and Drug Administration in 1987 for the treatment of hypercholesteraemia, in the treatment of Nf1-related fracture healing abnormalities. The experimental model presented here constitutes a valuable tool for the pre-clinical stage testing of candidate drugs, targeting Nf1-associated bone dysplasia.</p

Immune Response and Mitochondrial Metabolism Are Commonly Deregulated in DMD and Aging Skeletal Muscle

Duchenne Muscular Dystrophy (DMD) is a complex process involving multiple pathways downstream of the primary genetic insult leading to fatal muscle degeneration. Aging muscle is a multifactorial neuromuscular process characterized by impaired muscle regeneration leading to progressive atrophy. We hypothesized that these chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsies from four young DMD and four AGED subjects were referred to a group of seven muscle biopsies from young subjects without any neuromuscular disorder and explored through a dedicated expression microarray. We identified 528 differentially expressed genes (out of 2,745 analyzed), of which 328 could be validated by an exhaustive meta-analysis of public microarray datasets referring to DMD and Aging in skeletal muscle. Among the 328 validated co-expressed genes, 50% had the same expression profile in both groups and corresponded to immune/fibrosis responses and mitochondrial metabolism. Generalizing these observed meta-signatures with large compendia of public datasets reinforced our results as they could be also identified in other pathological processes and in diverse physiological conditions. Focusing on the common gene signatures in these two atrophying conditions, we observed enrichment in motifs for candidate transcription factors that may coordinate either the immune/fibrosis responses (ETS1, IRF1, NF1) or the mitochondrial metabolism (ESRRA). Deregulation in their expression could be responsible, at least in part, for the same transcriptome changes initiating the chronic muscle atrophy. This study suggests that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors

Promoting large multinational academic clinical trials for gastrointestinal cancers in Europe: the ENGIC (European Network for GI Cancers) initiative

This paper outlines proposals for the setup of a European Network for Gastro-Intestinal Cancers (ENGIC) initiative, aiming at promoting and fostering strategic academic clinical trials for gastrointestinal cancers in Europe. We discuss the presentation of the network, its main objectives, organization, internal/external processes, operational activities, governance and, finally, priority actions for the future. We propose that this provides a model that could be adopted by researchers working in other disease areas

Neutral chiral cyclopentadienyl Ru(II)Cl catalysts enable enantioselective [2+2]-cycloadditions

Cyclopentadienyl ruthenium(II) complexes with a large number of available coordination sites are frequently used catalysts for a broad range of transformations. To be able to render these transformations enantioselective, we have designed a chiral neutral (CpRu)-Ru-x(II) Cl complex basing on an atropchiral cyclopentadienyl (Cp-x) ligand which is accessed in a streamlined C-H functionalisation approach. The catalyst displays excellent levels of reactivity and enantioselectivity for enantioselective [2+2]-cycloadditions leading to strained chiral cyclobutenes, allowing for catalyst loadings as low as 1 mol%. A very strong counterion effect of a bound chloride anion transforms the corresponding unselective cationic complex into a highly enantioselective neutral version. Moreover, by adding norbornadiene at the end of the reaction the catalyst can be recovered and subsequently reused

NOA1 is an essential GTPase required for mitochondrial protein synthesis.

Contains fulltext : 97146.pdf (publisher's version ) (Open Access)Nitric oxide associated-1 (NOA1) is an evolutionarily conserved guanosine triphosphate (GTP) binding protein that localizes predominantly to mitochondria in mammalian cells. On the basis of bioinformatic analysis, we predicted its possible involvement in ribosomal biogenesis, although this had not been supported by any experimental evidence. Here we determine NOA1 function through generation of knockout mice and in vitro assays. NOA1-deficient mice exhibit midgestation lethality associated with a severe developmental defect of the embryo and trophoblast. Primary embryonic fibroblasts isolated from NOA1 knockout embryos show deficient mitochondrial protein synthesis and a global defect of oxidative phosphorylation (OXPHOS). Additionally, Noa1⁻/⁻ cells are impaired in staurosporine-induced apoptosis. The analysis of mitochondrial ribosomal subunits from Noa1⁻/⁻ cells by sucrose gradient centrifugation and Western blotting showed anomalous sedimentation, consistent with a defect in mitochondrial ribosome assembly. Furthermore, in vitro experiments revealed that intrinsic NOA1 GTPase activity was stimulated by bacterial ribosomal constituents. Taken together, our data show that NOA1 is required for mitochondrial protein synthesis, likely due to its yet unidentified role in mitoribosomal biogenesis. Thus, NOA1 is required for such basal mitochondrial functions as adenosine triphosphate (ATP) synthesis and apoptosis