365 research outputs found

    Recruitment of ubiquitin-activating enzyme UBA1 to DNA by poly(ADP-ribose) promotes ATR signalling

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    The DNA damage response (DDR) ensures cellular adaptation to genotoxic insults. In the crowded environment of the nucleus, the assembly of productive DDR complexes requires multiple protein modifications. How the apical E1 ubiquitin activation enzyme UBA1 integrates spatially and temporally in the DDR remains elusive. Using a human cell-free system, we show that poly(ADP-ribose) polymerase 1 promotes the recruitment of UBA1 to DNA. We find that the association of UBA1 with poly(ADP-ribosyl)ated protein–DNA complexes is necessary for the phosphorylation replication protein A and checkpoint kinase 1 by the serine/threonine protein kinase ataxia-telangiectasia and RAD3-related, a prototypal response to DNA damage. UBA1 interacts directly with poly(ADP-ribose) via a solvent-accessible and positively charged patch conserved in the Animalia kingdom but not in Fungi. Thus, ubiquitin activation can anchor to poly(ADP-ribose)-seeded protein assemblies, ensuring the formation of functional ataxia-telangiectasia mutated and RAD3-related-signalling complexes

    Label-free detection of anticancer drug paclitaxel in living cells by confocal Raman microscopy

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    Confocal Raman microscopy, a non-invasive, label-free, and high spatial resolution imaging technique is employed to trace the anticancer drug paclitaxel in living Michigan Cancer Foundation-7 (MCF-7) cells. The Raman images were treated by K-mean cluster analysis to detect the drug in cells. Distribution of paclitaxel in cells is verified by calculating the correlation coefficient between the reference spectrum of the drug and the whole Raman image spectra. A time dependent gradual diffusion of paclitaxel all over the cell is observed suggesting a complementary picture of the pharmaceutical action of this drug based on rapid binding of free tubulin to crystallized paclitaxel. (C) 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4794871

    Chemical, enantioselective, and sensory analysis of a cholinesterase inhibitor essential oil from coreopsis triloba S.F. Blake (asteraceae)

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    The fresh leaves of Coreopsis triloba S.F. Blake, collected at Cerro Villonaco in Loja, Ecuador, were investigated with respect to their essential oil (EO). The chemical composition was determined qualitatively through gas chromatography coupled with mass spectrometry (GC-MS) and quantitatively by gas chromatography coupled with flame ionization (GC-FID), using relative response factors (RRF) based on the enthalpy of combustion. The essential oil contained between 92.5% and 93.4% of monoterpene hydrocarbons, with (E)-β-ocimene being the main component (35.2–35.9%), followed by β-phellandrene (24.6–25.0%), α-pinene (15.3–15.9%), myrcene (10.9–11.0%), sabinene (2.2–2.4%), (Z)-β-ocimene (1.5%), and germacrene D (1.2–1.3%). The enantiomeric distribution of α-pinene, β-pinene, limonene, and germacrene D was also determined. The main components responsible for the aroma were identified through aroma extract dilution analysis (AEDA), a gas chromatography-olfactometry (GC-O) based technique, being α-pinene, β-pinene (0.6%), terpinolene (0.1%), α-copaene (0.1–0.3%), β-phellandrene, and (E)-4,8-dimethyl-1,3,7-nonatriene (0.1–0.2%) the main olfactory constituents according to the decreasing factor of dilution (FD) order. The biological tests showed IC50 inhibition values of 42.2 and 6.8 µg/mL for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively

    Mechanical Analysis of WEST divertor support plate

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    The Tore Supra tokamak is being transformed in an x-point divertor fusion device in the frame of the WEST (W-for tungsten-Environment in Steady-state Tokamak) project, launched in support to the ITER tungsten divertor strategy. The WEST project aims to test W monoblock Plasma Facing Units (PFU) under long plasma discharge (up to 1000s), with thermal loads of the same magnitude as those expected for ITER. Therefore the divertor is a key component of the WEST project, and so is its support structure, which has to handle strong mechanical loads. The WEST upper and lower divertor are made of 12 30° sectors, each one composed of 38 PFU that can be made of tungsten, CuCrZr or graphite. A generic 316L stainless steel 30° conic support plate is used to hold the 38 PFU together, regardless of their material. The PFUs are fixed on the support plate thanks to 152 Xm19 stainless steel fixing elements (4 per PFU), and in each of this fixing element an Aluminium-Nickel-Bronze alloy (Al-Ni-Br) pin is engaged in a slotted hole, in order to allow thermal expansion in the length direction of the PFU. The support plate is fixed on the divertor coil casing thanks to 10 M10 screws. Mechanicals loads which act on the PFUs are transmitted to the support plate through the fixing elements. These loads are due to Vertical Displacement Event (VDE), disruptions and thermal expansion of the PFU. First the different load cases, PFU configurations and scenario are presented. Then an ANSYS plastic mechanical simulation is performed in order to validate the number of cycles of the support plate for each scenario: 30 000 cycles in steady-state and 3000 cycles in VDE. Finally reactions forces from the previous ANSYS simulation are used in order to calculate the stress in the M10 screws

    Asymmetry of Magnetosheath Flows and Magnetopause Shape During Low Alfvén Mach Number Solar Wind

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    Previous works have emphasized the significant influence of the solar wind Alfvén Mach number (MA) on magnetospheric dynamics. Here we report statistical, observational results that pertain to changes in the magnetosheath flow distribution and magnetopause shape as a function of solar wind MA and interplanetary magnetic field (IMF) clock angle orientation. We use all Cluster 1 data in the magnetosheath during the period 2001–2010, using an appropriate spatial superposition procedure, to produce magnetosheath flow distributions as a function of location in themagnetosheath relative to the IMF and other parameters. The results demonstrate that enhanced flows in the magnetosheath are expected at locations quasi-perpendicular to the IMF direction in the plane perpendicular to the Sun-Earth line; in other words, for the special case of a northward IMF, enhanced flows are observed on the dawn and dusk flanks of the magnetosphere, while much lower flows are observed above the poles. The largest flows are adjacent to themagnetopause. Using appropriate magnetopause crossing lists (for both high and lowMA), we also investigate the changes inmagnetopause shape as a function of solarwindMA and IMF orientation. Comparing observed magnetopause crossings with predicted positions from an axisymmetric semi-empirical model, we statistically show that the magnetopause is generally circular during high MA, while is it elongated (albeit with moderate statistical significance) along the direction of the IMF during low MA. These findings are consistent with enhanced magnetic forces that prevail in the magnetosheath during lowMA. The component of the magnetic forces parallel to the magnetopause produces the enhanced flows along and adjacent to the magnetopause, while the component normal to the magnetopause exerts an asymmetric pressure on the magnetopause that deforms it into an elongated shape

    Design and Tests of 500kW RF Windows for the ITER LHCD System

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    In the frame of a R\&D effort conducted by CEA toward the design and the qualification of a 5 GHz LHCD system for the ITER tokamak, two 5 GHz 500 kW/5 s windows have been designed, manufactured and tested at high power in collaboration with the National Fusion Research Institute (NFRI). The window design rely on a symmetrical pill-box concept with a cylindrical beryllium oxide ceramic brazed on an actively water cooled copper skirt. The ceramic RF properties have been measured on a test sample to get realistic values for guiding the design. Low power measurements of the manufactured windows show return losses below-32 dB and insertion losses between-0.01 dB and-0.05 dB, with an optimum frequency shifted toward lower frequencies. High power tests conducted at NFRI show unexpected total power loss for both windows. The ceramic temperature during RF pulses has been found to reach unexpected high temperature, preventing these windows to be used under CW conditions. A post-mortem RF analysis of samples taken from one window shows that the dielectric properties of the ceramic were not the ones measured on the manufacturer sample, which partly explain the differences with the reference modelling
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