Faisabilité d'outils communs pour les SAGT de niveau 1 : analyse des projets Dor Breizh, Gutenberg, Aliénor et Sillon Mosellan

Ce document est une étude de faisabilité pour des outils communs à 4 projets de SAGT/1B (Dor Breizh, Gutenberg, Sillon Mosellan, Aliénor). L'étude est structurée en 3 phases : expression et analyse des besoins, architecture, organisation pour la mise en oeuvre. La partie 1 s'appuie sur des entretiens avec les responsables des 4 projets ; pour l'essentiel, il apparaît que les besoins fonctionnels sont communs aux 4 projets étudiés, en dehors de la coordination avec les partenaires locaux. La partie 2 étudie l'architecture des SAGT/1 de manière à mettre en évidence la faisabilité technique des outils communs ; l'architecture est appréhendée sous 3 aspects : fonctions, applications et architecture technique (environnement système, progiciels, etc.). L'étude analyse les solutions existantes, puis une architecture fonctionnelle, un découpage en applications et quelques recommandations techniques. La partie 3 décrit les principes d'organisation nécessaires à la mise en oeuvre des éventuels outils communs : définition des rôles (MOUV, MOE, REA, classiquement) aux niveaux local et central ; scénarios possibles de réutilisation d'applications communes à plusieurs SAGT ; calendrier et ressources prévisionnels. Compte tenu de l'avancement et du calendrier des projets, ainsi que de l'organisation actuelle du réseau technique de l'équipement, il est préconisé de mettre en place rapidement une équipe d'architectes pour les SAGT/1, qui contribuera à mettre en place progressivement des outils communs. En fin de document figurent un glossaire, une bibliographie, puis en annexe la grille d'entretien pour l'expression des besoins d'un projet SAGT/1, ainsi que la description des fonctions et des propositions de solutions pour les principales applications. Par souci de concision, on n'a pas repris ici les éléments généraux déjà présentés dans des rapports précédents du CERTU sur lesquels on s'est appuyés. Cette étude s'adresse en priorité aux responsables techniques du ministère de l'Équipement, soit dans les services et directions centraux chargés de définir une politique nationale pour l'informatique des CIGT, et le cas échéant de fournir à ces CIGT les outils appropriés, soit aux responsables de CIGT qui définissent, mettent en place et font évoluer les systèmes informatiques, quelles que soient les suites concrètes qui seront données aux propositions énoncées dans ce rapport. Par ailleurs, il peut également intéresser les entreprises et bureaux d'études qui spécifient et développent des applications, ainsi que les responsables d'autres systèmes d'aide à la gestion du trafic, notamment dans les collectivités ou les concessions d'autoroutes. Rappelons enfin qu'au stade actuel de la réflexion, ce rapport ne fait que proposer une approche et une organisation pour la définition d'une architecture informatique, et que d'une part les outils restent essentiellement à spécifier et à construire, d'autre part que le lecteur est prié de nous excuser par avance pour les erreurs et incomplétudes qui auront subsisté malgré de multiples relectures

Use of a beta microprobe system to measure arterial input function in PET via an arteriovenous shunt in rats

Kinetic modeling of physiological function using imaging techniques requires the accurate measurement of the time-activity curve of the tracer in plasma, known as the arterial input function (IF). The measurement of IF can be achieved through manual blood sampling, the use of small counting systems such as beta microprobes, or by derivation from PET images. Previous studies using beta microprobe systems to continuously measure IF have suffered from high background counts. In the present study, a light-insensitive beta microprobe with a temporal resolution of up to 1 s was used in combination with a pump-driven femoral arteriovenous shunt to measure IF in rats. The shunt apparatus was designed such that the placement of the beta microprobe was highly reproducible. The probe-derived IF was compared to that obtained from manual sampling at 5-s intervals and IF derived from a left ventricle VOI in a dynamic PET image of the heart. Probe-derived IFs were very well matched to that obtained by "gold standard" manual blood sampling, but with an increased temporal resolution of up to 1 s. The area under the curve (AUC) ratio between probe- and manually derived IFs was 1.07 ± 0.05 with a coefficient of variation of 0.04. However, image-derived IFs were significantly underestimated compared to the manually sampled IFs, with an AUC ratio of 0.76 ± 0.24 with a coefficient of variation of 0.32. IF derived from the beta microprobe accurately represented the IF as measured by blood sampling, was reproducible, and was more accurate than an image-derived technique. The use of the shunt removed problems of tissue-background activity, and the use of a light-tight probe with minimal gamma sensitivity refined the system. The probe/shunt apparatus can be used in both microprobe and PET studies

Introducing evolutionary biologists to the analysis of big data: guidelines to organize extended bioinformatics training courses

Research in evolutionary biology has been progressively influenced by big data such as massive genome and transcriptome sequencing data, scalar measurements of several phenotypes on tens to thousands of individuals, as well as from collecting worldwide environmental data at an increasingly detailed scale. The handling and analysis of such data require computational skills that usually exceed the abilities of most traditionally trained evolutionary biologists. Here we discuss the advantages, challenges and considerations for organizing and running bioinformatics training courses of 2–3 weeks in length to introduce evolutionary biologists to the computational analysis of big data. Extended courses have the advantage of offering trainees the opportunity to learn a more comprehensive set of complementary topics and skills and allowing for more time to practice newly acquired competences. Many organizational aspects are common to any course, as the need to define precise learning objectives and the selection of appropriate and highly motivated instructors and trainees, among others. However, other features assume particular importance in extended bioinformatics training courses. To successfully implement a learning-by-doing philosophy, sufficient and enthusiastic teaching assistants (TAs) are necessary to offer prompt help to trainees. Further, a good balance between theoretical background and practice time needs to be provided and assured that the schedule includes enough flexibility for extra review sessions or further discussions if desired. A final project enables trainees to apply their newly learned skills to real data or case studies of their interest. To promote a friendly atmosphere throughout the course and to build a close-knit community after the course, allow time for some scientific discussions and social activities. In addition, to not exhaust trainees and TAs, some leisure time needs to be organized. Finally, all organization should be done while keeping the budget within fair limits. In order to create a sustainable course that constantly improves and adapts to the trainees’ needs, gathering short- and long-term feedback after the end of the course is important. Based on our experience we have collected a set of recommendations to effectively organize and run extended bioinformatics training courses for evolutionary biologists, which we here want to share with the community. They offer a complementary way for the practical teaching of modern evolutionary biology and reaching out to the biological community.Peer reviewe

Automated synthesis of [18F] FBEM for labeling of thiol containing compounds

[18F]FBEM, i.e. N-[2-(4-[18F]fluorobenzamido)ethyl]maleimide, is a useful synthon employed for the specific radiolabeling of thiol containing compounds, including peptides and proteins. The aim of the present work was to develop a fast, reproducible and fully automated synthesis of this compound in order to improve its availabilty as well as for obvious radioprotection matters.Neofo

Assessment of the oxygen reactivity in a gas storage facility by multiphase reactive transport modeling of field data for air injection into a sandstone reservoir in the Paris Basin, France

International audienceThe first objective of this study is to present unique field data on a three-year pilot test during which air containing 8 mol% O2(g) was injected as a cushion gas into a natural gas reservoir, a carbonate-cemented sandstone aquifer lo- cated in the Paris Basin (France). 10-year system survey showed that: the oxygen was fully depleted several months after injection completion, meanwhile CO2(g) was detected around 2–6 mol%; the pH decreased from 8 to 6, while reducing conditions shifted to mildly oxidizing ones with increasing concentration of sulfates in equilibrium with gyp- sum. 3 years after injection completion, the pH gradually returned to its near initial state and sulfates were reduced by 2 to 3 times. The second objective is to develop a multiphase reactive transport model based on the field data. Simu- lations were constructed using the HYTEC reactive transport code, progressing from 0D-batch to 2D-reservoir config- urations. The model reproduced the gas-water-rock reactive sequence: 1/ full depletion of the injected O2(g) due to pyrite oxidation, 2/ leading to acidity production and dissolved sulfates, 3/ acidity buffering by calcite dissolution, 4/ followed by gypsum precipitation and CO2(g) exsolution. The model demonstrated that pyrite kinetics was the most significant factor governing not only the amount of O2(g), CO2(g) and dissolved minerals, but also the spatial ex- tent of these chemical reactions and, hence, the gas spread inside the reservoir. The formulated advective Damköhler number for oxygen consumption indicated advection- and reaction-dominant regimes explaining the gas composition and extension. The developed field-based model could be used as a workflow for other gas storage facilities, e.g. biomethane, compressed air, and CO2. For underground biomethane storage, the O2(g) contents recommended in Europe, i.e. the EASEE-gas specification 2005-001-02, should have a low impact on gas composition and reservoir geo- chemistry when the reservoir contains efficient pH-buffers such as calcite

Automated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors

TOPIC: Molecular Neuroimaging: from Bench to Bedside Automated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors Introduction: Dysfunction of the cerebral serotoninergic system is implicated in numerous neurodegenerative disorders such as Alzheimer disease’s, dementia, depression, anxiety, schizophrenia, and Parkinson disease’s. The 5-HT1A serotonin receptors are involved in several physiological functions including sleep, mood, neurogenesis and learning [1]. Consequently, there have been huge efforts in finding ligands for this receptor. [11C]WAY-100635 is a high affinity radioligand used for quantifying serotonin 5-HT1A receptors with positron emission tomography. An 18F-labeled radioligand is advantageous because of higher specific activity and physical/nuclear properties (t1/2= 109 min, 97% of positron decay and positron energy of 635 keV maximum). [18F]MPPF, a selective 5-HT1A antagonist derived from WAY-100635, is currently one of the most successful PET ligand used for 5-HT1A receptor imaging [2]. However the affinity is lower then WAY-100635 and the amount of [18F]MPPF reaching the brain is relatively low since MPPF is a substrate for p-glycoprotein [3]. Methods: In order to improve the brain uptake of the radiotracer, a desmethylated analog has been developed in our lab and preliminary in vitro studies show positive results [4]. Nevertheless, the radiosynthesis take place in two steps as a protecting group removal is needed. A one step procedure with a MPPF derivative could be of very great interest. We have synthesized many MPPF derivatives in our lab (modification on the phenylpiperazine moiety) and developed an automated radiosynthesis procedure for the production of these radiotracers. [18F]MPPF was chosen as the model compound. We used a GE Healthcare FASTlabTM module and made modifications to the [18F]FDG synthesis sequence and cassette. [18F]MPPF was synthesized by coupling of [18F]FBA with the corresponding amine. After coupling, the crude solution was diluted with water and passed through a tC18 cartridge for prepurification. After elution, the [18F]MPPF was purified by semi-preparative HPLC. Results: Total synthesis time, including purification was approximately 100 min. [18F]FBA and [18F]MPPF were obtained at a corrected yield of 55% (n=20) and 25% (n=5) respectively. The radiochemical purity, checked by radio-TLC and UPLC, was >95%. Conclusions: We have developed an automated method for [18F]MPPF and derivatives production using a commercial synthesizer (FASTlabTM from GE Healthcare) and a conventional HPLC system resulting in good yields and high (radio)chemical purity. By simply switching the vial containing the modified amine, an 18F-labeled MPPF derivative could be obtained. Radiosynthesis is still under optimization and the radiotracers synthesized need to be tested as suitable 5-HT1A radioligands. Acknowledgement: This work was supported by the Fondation Rahier. References: [1] Filip M., Bader M. et Al, Pharmacol Rep. 2009 Sep-Oct; 61(5):761-77 [2] Aznavour N, Zimmer L. Et Al, Neuropharmacology. 2007 Mar; 52(3):695-707 [3] Laćan G., Plenevaux A. et Al, Eur J Nucl Med Mol Imaging. 2008 Dec;35(12):2256-66 [4] Defraiteur C., Plenevaux A. et Al., Br J Pharmacol. 2007 Nov; 152(6):952-8Automated radiosynthesis of CNS ligands labeled with fluorine-1

Fast production of highly concentrated reactive [18F] fluoride for aliphatic and aromatic nucleophilic radiolabelling

The use of a polymeric solid support loaded with a long alkyl chain quaternary ammonium allows the rapid and efficient recovery of cyclotron produced [18F]F- from [18O]water to a low water content organic solution compatible with fast nucleophilic labelling of most precursors for PET radiopharmaceuticals in high yield