Ageing of polysulfone membranes in contact with bleach solution: Role of radical oxidation and of some dissolved metal ions

In water production plants using membrane processes, contact with chemicals such as chlorine plays an important role in membrane ageing. This experimental study was aimed at gaining a better understanding of the effect of hypochlorite cleaning solutions on the properties of a polysulfone ultrafiltration membrane. Accelerated ageing of the membrane was simulated by soaking it in chlorine solutions and the mechanical properties of the membrane were monitored versus soaking time. An oxidation mechanism is validated which involves the catalytic effect of dissolved metal ions and the inhibitor effect of an antioxidant when these are present in soaking solutions

Concentration et purification de macromolecules par ultrafiltration

SIGLECNRS T 55818 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Towards wide-field retinal imaging with adaptive optics

International audienceIn vivo imaging of the retina on humans by means of adaptive optics can lead to a significant gain in resolution. We demonstrate the realization and use of a system made of a Shack-Hartmann wavefront sensor carefully matched to a 13-actuator bimorph deformable mirror sensor, operating at a closed loop frequency of 70 Hz at lambda=835 nm. Even with this simple but optimized system with 12 degrees of freedom, correcting only aberrations of moderate orders, we routinely and systematically obtain retinal images containing spatial information up to half the diffraction limit frequency of a dilated (7 mm) iris at a lambda=550 nm wavelength (1.6 mum diffraction spot size). Signal-to-noise ratio on the images is limited by eye safety constraints, but is sufficient to reach the high-frequency information on single, short-exposure (7 ms) images, which clearly show individual cones and capillary details. Correction is highly depending on proper centering of the eye, achieved with an active target. Focusing through the retina is possible with a reduced depth of focus. Variability of moderate order aberrations among dilated subjects has been observed. Using an image fitting algorithm, individual images are used to build a wider field corrected image of the retina (~3°), possibly useful for diagnosis and microcirculation analysis

PHILAE: Science scheduling and unknown context. leassons learned

Rosetta is an ambitious mission launched in March 2004 to study the nucleus as well as the coma of the comet 67P/Churyumov-Gerasimenko. It is composed of a space probe and the Philae Lander. The mission is a series of premieres: among others, first probe to escort a comet, first time a landing site is selected with a so short notice, first time a lander has landed on a comet nucleus. The space probe Rosetta reached the vicinity of the comet in spring 2014 when it has started to study Churyumov-Gerasimenko with remote sensing instruments. An intense observation phase followed to be able to select a landing site for the Lander. And in November 2014, at a distance of about 3 AU from the sun, Philae has reached its destination on the surface of the comet 67P. Once stabilized on the comet, the lander has performed its “First Science sequence”. Philae’s aim was to perform detailed and innovative in-situ experiments on the comet’s surface to characterize the nucleus by performing mechanical, chemical and physical investigations on the comet surface. The main contribution to the Rosetta lander by the French space agency (CNES) is the Science Operation and Navigation Centre (SONC) located in Toulouse. Among its tasks is the scheduling of the scientific activities of the 10 lander experiments and then to provide it to the Lander Control Centre (LCC) located in DLR Cologne. Nevertheless, the specific context of the Rosetta mission made this task even more complex if compared to usual spacecraft or landers: indeed the teams in charge of the Philae activity scheduling had to cope with huge constraints in term of energy, data management, asynchronous processes and co-activities or exclusions between instruments. In addition to these huge constraints it is important to note that the comet, its environment and the landing conditions remained unknown until the separation time and that the landing site was selected a short time before it had to take place and when the baseline operational sequence was already designed. This paper will explain the specific context of the Rosetta lander mission and all the constraints that the activity scheduling had to face to fulfil the scientific objectives specified for Philae. A specific tool was developed by CNES and used to design the complete sequence of activities on the comet with respect to all constraints. The baseline scenario designed this way will also be detailed to highlight the difficulties and challenges that the operational team had to face. A specific focus will be given on the landing site selection and the impacts on the scientific operations scheduling. Moreover the actual sequence performed on the comet will also be detailed and analysed to deduce the lessons that could be learned from such an unprecedented endeavour. Indeed as for every mission of exploration the flexibility concept was anticipated but had to face unexpected events

The Philae Lander: Science planning and operations

Rosetta is an ambitious mission launched in March 2004 to study comet 67P/Churyumov–Gerasimenko. It is composed of a space probe (Rosetta) and the Philae Lander. The mission is a series of premieres: among others, first probe to escort a comet, first time a landing site is selected with short turnaround time, first time a lander has landed on a comet nucleus. In November 2014, once stabilized on the comet, Philae has performed its “First Science Sequence”. Philae’s aim was to perform detailed and innovative in-situ experi- ments on the comet’s surface to characterize the nucleus by performing mechanical, chemical and physical investigations on the comet surface. The main contribution to the Rosetta lander by the French space agency (CNES) is the Science Operation and Navigation Center (SONC) located in Toulouse. Among its tasks is the scheduling of the scientific activities of the 10 lander experiments and then to provide it to the Lander Control Center (LCC) located in DLR Cologne. The teams in charge of the Philae activity scheduling had to cope with considerable constraints in term of energy, data management, asynchronous processes and co-activities or exclusions between instruments. Moreover the comet itself, its environment and the landing conditions remained unknown until separation time. The landing site was selected once the operational sequence was already designed. This paper will explain the specific context of the Rosetta lander mission and all the constraints that the lander activity scheduling had to face to fulfill the scientific objectives specified for Philae. A specific tool was developed by CNES and used to design the complete sequence of activities on the comet with respect to all constraints. The baseline scenario for the lander operation will also be detailed as well as the sequence performed on the comet to highlight the difficulties and challenges that the operational team faced

Metabolism and Pharmacokinetics of EAPB0203 and EAPB0503, Two Imidazoquinoxaline Compounds Previously Shown to Have Antitumoral Activity on Melanoma and T-Lymphomas

International audienceFor several years, our group has been developing quinoxalinic compounds. Two of them, N-methyl-1-(2-phenethyl)imidazo[1,2-a]qui-noxalin-4-amine (EAPB0203) and 1-(3-methoxyphenyl)-N-methylimi-dazo[1,2-a]quinoxalin-4-amine (EAPB0503), have emerged as the most promising anticancer drugs. In the present work, we determined metabolism pathways using liver microsomes from four mam-malian species including human. We identified the cytochrome P450 isoform(s) involved in the metabolism and then investigated the phar-macokinetics and metabolism of EAPB0203 and EAPB0503 in rat after intravenous and intraperitoneal administration. Biotransformation of the compounds involved demethylation and hydroxylation reactions. Rat and dog metabolized the compounds at a higher rate than mouse and human. In all species, CYP1A1/2 and CYP3A isoforms were the predominant enzymes responsible for the metabolism. From human liver microsomes, unbound intrinsic clearances were approximately 56 ml/(min ⅐ g) protein. EAPB0203 and EAPB0503 were extensively bound to human plasma proteins, mainly human serum albumin (HSA) (ϳ98-99.5%). Thus, HSA could act as carrier of these compounds in human plasma. Scatchard plots showed patterns in which the plots yielded upwardly convex hyperbolic curves. On the basis of the Hill coefficients, there appears to be interaction between the binding sites of HSA, suggesting positive cooperativity. The main in vitro metabolites were identified in vivo. Total clearances of EAPB0203 and EAPB0503 [3.2 and 2.2 l/(h ⅐ kg), respectively] were notably lower than the typical cardiac plasma output in rat. The large volumes of distribution of these compounds (4.3 l/kg for EAPB0203 and 2.5 l/kg for EAPB0503) were consistent with extensive tissue binding. After intraperitoneal administration, bioavailability was 22.7% for EAPB0203 and 35% for EAPB0503 and a significant hepatic first-pass effect occurred

TLR3 deficiency in herpes simplex encephalitis: High allelic heterogeneity and recurrence risk

Objective: To determine the proportion of children with herpes simplex encephalitis (HSE) displaying TLR3 deficiency, the extent of TLR3 allelic heterogeneity, and the specific clinical features of TLR3 deficiency. Methods: We determined the sequence of all exons of TLR3 in 110 of the 120 patients with HSE enrolled in our study who do not carry any of the previously described HSE-predisposing mutations of TLR3 pathway genes (TLR3, UNC93B1, TRIF, TRAF3, and TBK1). All the new mutant TLR3 alleles detected were characterized experimentally in-depth to establish the causal relationship between the genotype and phenotype. Results: In addition to the 3 previously reported TLR3-deficient patients from the same cohort, 6 other children or young adults with HSE carry 1 of 5 unique or extremely rare (minor allele frequency ,0.001) missense TLR3 alleles. Two alleles (M374T, D592N) heterozygous in 3 patients are not deleterious in vitro. The other 3 are deleterious via different mechanisms: G743D1R811I and L360P heterozygous in 2 patients are loss-of-function due to low levels of expression and lack of cleavage, respectively, and R867Q homozygous in 1 patient is hypomorphic. The 3 patients' fibroblasts display impaired TLR3 responses and enhanced herpes simplex virus 1 susceptibility. Overall, TLR3 deficiency is therefore found in 6 (5%) of the 120 patients studied. There is high allelic heterogeneity, with 3 forms of autosomal dominant partial defect by negative dominance or haploinsufficiency, and 2 forms of autosomal recessive defect with complete or partial deficiency. Finally, 4 (66%) of the 6 TLR3-deficient patients had at least 1 late relapse of HSE, whereas relapse occurred in only 12 (10%) of the total cohort of 120 patients. Conclusions: Childhood-onset HSE is due to TLR3 deficiency in a traceable fraction of patients, in particular the ones with HSE recurrence. Mutations in TLR3 and TLR3 pathway genes should be searched and experimentally studied in children with HSE, and patients with proven TLR3 deficiency should be followed carefully.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Test-retest resting-state fMRI in healthy elderly persons with a family history of Alzheimer’s disease

We present a test-retest dataset of resting-state fMRI data obtained in 80 cognitively normal elderly volunteers enrolled in the “Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer's Disease” (PREVENT-AD) Cohort. Subjects with a family history of Alzheimer's disease in first-degree relatives were recruited as part of an on-going double blind randomized clinical trial of Naproxen or placebo. Two pairs of scans were acquired ~3 months apart, allowing the assessment of both intra- and inter-session reliability, with the possible caveat of treatment effects as a source of inter-session variation. Using the NeuroImaging Analysis Kit (NIAK), we report on the standard quality of co-registration and motion parameters of the data, and assess their validity based on the spatial distribution of seed-based connectivity maps as well as intra- and inter-session reliability metrics in the default-mode network. This resource, released publicly as sample UM1 of the Consortium for Reliability and Reproducibility (CoRR), will benefit future studies focusing on the preclinical period preceding the appearance of dementia in Alzheimer's disease