Inhibitor of growth protein 3 epigenetically silences endogenous retroviral elements and prevents innate immune activation

Endogenous retroviruses (ERVs) are subject to transcriptional repression in adult tissues, in part to prevent autoimmune responses. However, little is known about the epigenetic silencing of ERV expression. Here, we describe a new role for inhibitor of growth family member 3 (ING3), to add to an emerging group of ERV transcriptional regulators. Our results show that ING3 binds to several ERV promoters (for instance MER21C) and establishes an EZH2-mediated H3K27 trimethylation modification. Loss of ING3 leads to decreases of H3K27 trimethylation enrichment at ERVs, induction of MDA5-MAVS-interferon signaling, and functional inhibition of several virus infections. These data demonstrate an important new function of ING3 in ERV silencing and contributing to innate immune regulation in somatic cells

Qualification and characterization of electronics of the fast neutron Hodoscope detectors using neutrons from CABRI core

The study of Reactivity Initiated Accidents (RIA) is important to determine up to which limits nuclear fuels can withstand such accidents without clad failure. The CABRI International Program (CIP), conducted by IRSN under an OECD/NEA agreement, has been launched to perform representative RIA Integral Effect Tests (IET) on real irradiated fuel rods in prototypical Pressurized Water Reactors (PWR) conditions. For this purpose, the CABRI experimental pulse reactor, operated by CEA in Cadarache, France, has been strongly renovated, and equipped with a pressurized water loop. The behavior of the test rod, located in that loop in the center of the driver core, is followed in real time during the power transients thanks to the hodoscope, a unique online fuel motion monitoring system, and one of the major distinctive features of CABRI. The hodoscope measures the fast neutrons emitted by the tested rod during the power pulse with a complete set of 153 Fission Chambers and 153 Proton Recoil Counters. During the CABRI facility renovation, the electronic chain of these detectors has been upgraded. In this paper, the performance of the new system is presented describing gain calibration methodology in order to get maximal Signal/Noise ratio for amplification modules, threshold tuning methodology for the discrimination modules (old and new ones), and linear detectors response limit versus different reactor powers for the whole electronic chain

The CABRI fast neutron Hodoscope: Renovation, qualification program and first results following the experimental reactor restart

The CABRI experimental pulse reactor, located at the Cadarache nuclear research center, southern France, is devoted to the study of Reactivity Initiated Accidents (RIA). For the purpose of the CABRI International Program (CIP), managed and funded by IRSN, in the framework of an OECD/NEA agreement, a huge renovation of the facility has been conducted since 2003. The Cabri Water Loop was then installed to ensure prototypical Pressurized Water Reactor (PWR) conditions for testing irradiated fuel rods. The hodoscope installed in the CABRI reactor is a unique online fuel motion monitoring system, operated by IRSN and dedicated to the measurement of the fast neutrons emitted by the tested rod during the power pulse. It is one of the distinctive features of the CABRI reactor facility, which is operated by CEA. The system is able to determine the fuel motion, if any, with a time resolution of 1 ms and a spatial resolution of 3 mm. The hodoscope equipment has been upgraded as well during the CABRI facility renovation. This paper presents the main outcomes achieved with the hodoscope since October 2015, date of the first criticality of the CABRI reactor in its new Cabri Water Loop configuration. Results obtained during reactor commissioning phase functioning, either in steady-state mode (at low and high power, up to 23 MW) or in transient mode (start-up, possibly beyond 20 GW), are discussed

GluA4-Targeted AAV Vectors Deliver Genes Selectively to Interneurons while Relying on the AAV Receptor for Entry

Selective gene delivery into subtypes of interneurons remains an important challenge in vector development. Adeno-associated virus (AAV) vector particles are especially promising for intracerebral injections. For cell entry, AAV2 particles are supposed to attach to heparan-sulfate proteoglycans (HSPGs) followed by endocytosis via the AAV receptor (AAVR). Here, we assessed engineered AAV particles deficient in HSPG attachment but competent in recognizing the glutamate receptor 4 (GluA4, also known as GluRD or GRIA4) through a displayed GluA4-specific DARPin (designed ankyrin repeat protein). When injected into the mouse brain, histological evaluation revealed that in various regions, more than 90% of the transduced cells were interneurons, mainly of the parvalbumin-positive subtype. Although part of the selectivity was mediated by the DARPin, the chosen spleen focus-forming virus (SFFV) promoter had contributed as well. Further analysis revealed that the DARPin mediated selective attachment to GluA4-positive cells, whereas gene delivery required expression of AAVR. Our data suggest that cell selectivity of AAV particles can be modified rationally and efficiently through DARPins, but expression of the AAV entry receptor remains essential

Development of a new bench for puncturing of irradiated fuel rods in STAR hot laboratory

A new device for puncturing of irradiated fuel rods in commercial power plants has been designed by Fuel Research Department of CEA Cadarache in order to provide experimental data of high precision on fuel pins with various designs. It will replace the current set-up that has been used since 1998 in hot cell 2 of STAR facility with more than 200 rod puncturing experiments. Based on this consistent experimental feedback, the heavy-duty technique of rod perforation by clad punching has been preserved for the new bench. The method of double expansion of rod gases is also retained since it allows upgrading the confidence interval of volumetric results obtained from rod puncturing. Furthermore, many evolutions have been introduced in the new design in order to improve its reliability, to make the maintenance easier by remote handling and to reduce experimental uncertainties. Tightness components have been studied with Sealing Laboratory Maestral at Pierrelatte so as to make them able to work under mixed pressure conditions (from vacuum at 10-5 mbar up to pressure at 50 bars) and to lengthen their lifetime under permanent gamma irradiation in hot cell. Bench ergonomics has been optimized to make its operating by remote handling easier and to secure the critical phases of a puncturing experiment. A high pressure gas line equipped with high precision pressure sensors out of cell can be connected to the bench in cell for calibration purposes. Uncertainty analyses using Monte Carlo calculations have been performed in order to optimize capacity of the different volumes of the apparatus according to volumetric characteristics of the rod to be punctured. At last this device is composed of independent modules which allow puncturing fuel pins out of different geometries (PWR, BWR, VVER). After leak tests of the device and remote handling simulation in a mock-up cell, several punctures of calibrated specimens have been performed in 2016. The bench will be implemented soon in hot cell 2 of STAR facility for final qualification tests. PWR rod punctures are already planned for 2018

Can modern infrared analyzers replace gas chromatography to measure anesthetic vapor concentrations?

<p>Abstract</p> <p>Background</p> <p>Gas chromatography (GC) has often been considered the most accurate method to measure the concentration of inhaled anesthetic vapors. However, infrared (IR) gas analysis has become the clinically preferred monitoring technique because it provides continuous data, is less expensive and more practical, and is readily available. We examined the accuracy of a modern IR analyzer (M-CAiOV compact gas IR analyzer (General Electric, Helsinki, Finland) by comparing its performance with GC.</p> <p>Methods</p> <p>To examine linearity, we analyzed 3 different concentrations of 3 different agents in O₂: 0.3, 0.7, and 1.2% isoflurane; 0.5, 1, and 2% sevoflurane; and 1, 3, and 6% desflurane. To examine the effect of carrier gas composition, we prepared mixtures of 1% isoflurane, 1 or 2% sevoflurane, or 6% desflurane in 100% O₂(= O₂group); 30%O₂+ 70%N₂O (= N₂O group), 28%O₂+ 66%N₂O + 5%CO₂(= CO₂group), or air. To examine consistency between analyzers, four different M-CAiOV analyzers were tested.</p> <p>Results</p> <p>The IR analyzer response in O₂is linear over the concentration range studied: IR isoflurane % = -0.0256 + (1.006 * GC %), R = 0.998; IR sevoflurane % = -0.008 + (0.946 * GC %), R = 0.993; and IR desflurane % = 0.256 + (0.919 * GC %), R = 0.998. The deviation from GC calculated as (100*(IR-GC)/GC), in %) ranged from -11 to 11% for the medium and higher concentrations, and from -20 to +20% for the lowest concentrations. No carrier gas effect could be detected. Individual modules differed in their accuracy (p = 0.004), with differences between analyzers mounting up to 12% of the medium and highest concentrations and up to 25% of the lowest agent concentrations.</p> <p>Conclusion</p> <p>M-CAiOV compact gas IR analyzers are well compensated for carrier gas cross-sensitivity and are linear over the range of concentrations studied. IR and GC cannot be used interchangeably, because the deviations between GC and IR mount up to ± 20%, and because individual analyzers differ unpredictably in their performance.</p

Gamma-ray spectroscopy measurements and simulations for uranium mining

AREVA Mines and the Nuclear Measurement Laboratory of CEA Cadarache are collaborating to improve the sensitivity and precision of uranium concentration evaluation by means of gamma measurements. This paper reports gamma-ray spectra, recorded with a high-purity coaxial germanium detector, on standard cement blocks with increasing uranium content, and the corresponding MCNP simulations. The detailed MCNP model of the detector and experimental setup has been validated by calculation vs. experiment comparisons. An optimization of the detector MCNP model is presented in this paper, as well as a comparison of different nuclear data libraries to explain missing or exceeding peaks in the simulation. Energy shifts observed between the fluorescence X-rays produced by MCNP and atomic data are also investigated. The qualified numerical model will be used in further studies to develop new gamma spectroscopy approaches aiming at reducing acquisition times, especially for ore samples with low uranium content

Global gene disruption in human cells to assign genes to phenotypes

Insertional mutagenesis in a haploid background can disrupt gene function[superscript 1]. We extend our earlier work by using a retroviral gene-trap vector to generate insertions in >98% of the genes expressed in a human cancer cell line that is haploid for all but one of its chromosomes. We apply phenotypic interrogation via tag sequencing (PhITSeq) to examine millions of mutant alleles through selection and parallel sequencing. Analysis of pools of cells, rather than individual clones[superscript 1] enables rapid assessment of the spectrum of genes involved in the phenotypes under study. This facilitates comparative screens as illustrated here for the family of cytolethal distending toxins (CDTs). CDTs are virulence factors secreted by a variety of pathogenic Gram-negative bacteria responsible for tissue damage at distinct anatomical sites[superscript 2]. We identify 743 mutations distributed over 12 human genes important for intoxication by four different CDTs. Although related CDTs may share host factors, they also exploit unique host factors to yield a profile characteristic for each CDT

On decoding and rewriting genomes: a psychoanalytical reading of a scientific revolution

In various documents the view emerges that contemporary biotechnosciences are currently experiencing a scientific revolution: a massive increase of pace, scale and scope. A significant part of the research endeavours involved in this scientific upheaval is devoted to understanding and, if possible, ameliorating humankind: from our genomes up to our bodies and brains. New developments in contemporary technosciences, such as synthetic biology and other genomics and “post-genomics” fields, tend to blur the distinctions between prevention, therapy and enhancement. An important dimension of this development is “biomimesis”: i.e. the tendency of novel technologies and materials to mimic or plagiarize nature on a molecular and microscopic level in order to optimise prospects for the embedding of technological artefacts in natural systems such as human bodies and brains. In this paper, these developments are read and assessed from a psychoanalytical perspective. Three key concepts from psychoanalysis are used to come to terms with what is happening in research laboratories today. After assessing the general profile of the current revolution in this manner, I will focus on a particular case study, a line of research that may serve as exemplification of the vicissitudes of contemporary technosciences, namely viral biomaterials. Viral life forms can be genetically modified (their genomes can be rewritten) in such a manner that they may be inserted in human bodies in order to produce substances at specific sites such as hormones (testosterone), neurotransmitters (dopamine), enzymes (insulin) or bone and muscle tissue. Notably, certain target groups such as top athletes, soldiers or patients suffering from degenerative diseases may become the pioneers serving as research subjects for novel applications. The same technologies can be used for various purposes ranging from therapy up to prevention and enhancement