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

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

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)

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

Design and RF measurements of a 5 GHz 500 kW window for the ITER LHCD system

International audienceCEA/IRFM is conducting R&D efforts in order to validate the critical RF components of the 5 GHz ITER LHCD system, which is expected to transmit 20 MW of RF power to the plasma. Two 5 GHz 500 kW BeO pill-box type window prototypes have been manufactured in 2012 by the PMB Company, in close collaboration with CEA/IRFM. Both windows have been validated at low power, showing good agreement between measured and modeling, with a return loss better than 32 dB and an insertion loss below 0.05 dB. This paper reports on the window RF design and the low power measurements. The high power tests up to 500kW have been carried out in March 2013 in collaboration with NFRI. Results of these tests are also reported. In the current ITER LHCD design, 20 MW Continuous Wave (CW) of Radio-Frequency power at 5 GHz are expected to be generated and transmitted to the plasma. In order to separate the vacuum vessel pressure from the cryostat waveguide pressure, forty eight 5 GHz 500kW CW windows are to be assembled on the waveguides at the equatorial port flange. For nuclear safety reasons, forty eight additional windows could be located in the cryostat section, to separate and monitor the cryostat waveguide pressure from the exterior transmission line pressure. These windows are identified as being one of the main critical components for the ITER LHCD system since first ITER LHCD studies [1] [2] [3] or more recently [4] [5] , and clearly require an important R&D effort. In this context and even if the LHCD system is not part of the construction baseline, the CEA/IRFM is conducting a R&D effort in order to validate a design and the performances of these RF windows. In order to begin the assessment of this need, two 5 GHz 500 kW/5 s pill-box type windows prototypes have been manufactured in 2012 by the PMB Company in close collaboration with the CEA/IRFM [6]. The section 2 of this paper reports the RF and mechanical design of a 5 GHz window. Some features of the mechanical design and the experimental RF measurements at low power are reported in section 3. High power results, made in collaboration with NFRI, are detailed in section 4. The development of CW windows is discussed in the conclusion. 2-RF AND MECHANICAL DESIGN The proposed 5 GHz RF window is based on a pill-box design [2] , i.e. a ceramic brazed in portion of a circular waveguide, connected on either side to a rectangular waveguide section. Typical design rules of thumb of such device are circular section diameter about the same size of the diagonal of the rectangular waveguide (cf. FIGURE 1). Without taking into account the ceramic, the circular section length is approximately half a guided wavelength of the circular TE 11 mode, in order for the device to act as a half-wave transformer. Once optimized, taking into account the ceramic, matching is correct only for a narrow band of frequency and is very sensitive to the device dimensions and the ceramic relative permittivity. The heat losses in the ceramic, which have to be extracted by an active water cooling, depends on the inside electric field topology and of ceramic dielectric loss (loss tangent). Undesirable modes due to parasitic resonances can be excited in the ceramic volume, raising the electric field an

Special Care and School Difficulties in 8-Year-Old Very Preterm Children: The Epipage Cohort Study

OBJECTIVES: To investigate school difficulties, special care and behavioral problems in 8 year-old very preterm (VPT) children. PATIENT AND METHODS: Longitudinal population-based cohort in nine regions of France of VPT children and a reference group born at 39-40 weeks of gestation (WG). The main outcome measures were information about school, special care and behavioral problems using Strengths and Difficulties Questionnaire from a questionnaire to parents. RESULTS: Among the 1439 VPT children, 5% (75/1439) were in a specialised school or class, 18% (259/1439) had repeated a grade in a mainstream class and 77% (1105/1439) were in the appropriate grade-level in mainstream class; these figures were 1% (3/327) , 5% (16/327) and 94% (308/327) , respectively, for the reference group. Also, 15% (221/1435) of VPT children in a mainstream class received support at school versus 5% (16/326) of reference group. More VPT children between the ages of five and eight years received special care (55% (794/1436)) than children born at term (38% (124/325)); more VPT children (21% (292/1387)) had behavioral difficulties than the reference group (11% (35/319)). School difficulties, support at school, special care and behavioral difficulties in VPT children without neuromotor or sensory deficits varied with gestational age, socioeconomic status, and cognitive score at the age of five. CONCLUSIONS: Most 8-year-old VPT children are in mainstream schools. However, they have a high risk of difficulty in school, with more than half requiring additional support at school and/or special care. Referral to special services has increased between the ages of 5 and 8 years, but remained insufficient for those with borderline cognitive scores

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

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

Innovative tools and modeling methodology for impact prediction and assessment of the contribution of materials on indoor air quality

International audienceBackground: The combination of more and more airtight buildings and the emission of formaldehyde and other volatile organic compounds (VOCs) by building, decoration and furniture materials lead to lower indoor air quality. Hence, it is an important challenge for public health but also for the preservation of cultural heritage, as for example, artworks in museum showcases and other cultural objects. Indeed, some VOCs such as organic acids or carbonyl compounds may play a role in the degradation of some metallic objects or historic papers. Thus, simple and cost effective sampling tools are required to meet the recent and growing demand of on-site diagnostic of indoor air quality , including emission source identification and their ranking.Results: In this aim, we developed new tools based on passive sampling (Solid-Phase Micro Extraction, SPME) to measure carbonyls compounds (including formaldehyde) and other VOCs and both in indoor air and at the material/ air interface. On one hand, the coupling of SPME with a specially designed emission cell allows the screening and the quantification of the VOCs emitted by building, decoration or furniture materials. On the other hand, indoor air is simply analysed using new vacuum vial sampling combined with VOCs pre-concentration by SPME. These alternative sampling methods are energy free, compact, silent and easy to implement for on-site measurements. They show satisfactory analytical performance as detection limits range from 0.05 to 0.1 µg m −3 with an average Relative Standard Deviation (RSD) of 18 %. They already have been applied to monitoring of indoor air quality and building material emissions for a 6 months period. The data obtained were in agreement with the prediction of a physical monozonal model which considers building materials both as VOC sources and sinks and air exchange rate in one single room ("box model").Conclusion: Results are promising, even if more data are required to complete validation, and the model could be envisaged as a predictive tool for indoor air quality. This new integrated approach involving measurements and mod-eling could be easily transposed to historic environments and to the preservation of cultural heritage

Geochemical, multi-isotopic and hydrogeological characterization of mineralized groundwaters, Entre-deux-Mers area, Gironde (SW France).

Groundwater quality sustainability In the south-west of France, the Eocene aquifer is one of the main resources for irrigation, thermo-mineral water, and mainly for drinking water in the Bordeaux region. This aquifer is characterized by the presence of a large mineralized area, centered on the Entre-deux-Mers region, between the Garonne and the Dordogne rivers, where the groundwaters show strong mineralization and anomalous levels of critical elements, such as sulphates and fluoride, leading to difficulties of resource exploitation for drinking water supply. Ongoing analyses of major elements confirm the salinity variation in the system and the multi-isotopes results will be presented at the conference, in order to decipher the origin of this salinity