Kinetic Modeling of Vacuum Gas Oil Hydrotreatment using a Molecular Reconstruction Approach

International audienceVacuum Gas Oils (VGO) are heavy petroleum cuts (boiling points ranging from 350 to 550 ˚C) that can be transformed into valuable fuels (gasolines, diesels) by fluid catalytic cracking or hydrocracking. Prior to these conversion processes, hydrotreating is required in order to eliminate the impurities in VGOs. The hydrotreatment process enables to meet the environmental specifications (total sulfur contents) and to prevent nitrogen poisoning of conversion catalysts. In order to develop a kinetic model based on an accurate VGOs molecular description, innovative analytical tools and molecular reconstruction techniques were used in this work. A lumped model using a Langmuir-Hinshelwood representation was developed for hydrodearomatization, hydrodesulfurization and hydrodenitrogenation of the VGO. This lumped model was successfully applied to the experimental feed pretreatment data and was able to predict evolution of concentration of the aromatics, nitrogen and sulfur species

A single events microkinetic model for hydrocracking of vacuum gas oil

International audienceThe single events microkinetic modeling approach is extended to include saturated and unsaturated cyclic molecules, in addition to straight chained paraffins. The model is successfully applied to hydrocracking (HCK) of a hydrotreated Vacuum Gas Oil (VGO) residue in a pilot plant, under industrial operating conditions, on a commercial bi-functional catalyst. The molecular composition of the VGO feed is obtained by reconstruction based on a combination of analytical data (SIMDIS, GCxGC, mass spectroscopy). The necessary extensions to the single events methodology, which has previously only been applied to much simpler reacting systems (i.e. HCK of paraffins) are detailed in this work. Feeds typically used in the petrochemical industry typically contain a far more complex mixture of hydrocarbons, including cyclic species (i.e. naphtenes & aromatics). A more complex reaction network is therefore required in order to apply a single events model to such feeds. Hydrogenation, as well as endo-and exo-cyclic reactions have been added to the well-known acyclic β-scission and PCP-isomerization reactions. A model for aromatic ring hydrogenation was included in order to be able to simulate the reduction in aromatic rings, which is an important feature of HCK units. The model was then applied to 8 mass balances with a wide range of residue conversion (20 – 90%). The single events model is shown to be capable of correctly simulate the macroscopic effluent characteristics, such as residue conversion, yield structure, and weight distribution of paraffinic, naphthenic, and aromatic compounds in the standard cuts. This validates the overall model. The single events model provides far more detail about the fundamental chemistry of the system. This is shown in a detailed analysis of the reaction kinetics. The evolution of molecule size (i.e. carbon number), number of saturated/unsaturated rings, or the ratio of branched and un-branched species can be followed along the reactor. This demonstrates the explanatory power of this type of model. Calculations are performed on the IFPEN high performance computing cluster, with parallelization via MPI (message passing interface). This was very useful in order to reduce time consuming problems especially for the parameter fitting step.

Maturity integrated in a meta model of knowledge to help decision making in preliminary collaborative design of mechanical systems

La conception de systèmes mécaniques, de par son aspect pluridisciplinaire et technologique, fait intervenir et interagir différentes personnes qui travaillent et prennent des décisions ensemble, et, participent ensemble à l élaboration du produit. Elles travaillent de manière collaborative cependant elles ne se connaissent pas obligatoirement, ne se situent pas forcément géographiquement sur un site commun, n ont peut-être pas la même culture et n appartiennent pas systématiquement à la même entreprise. La conception préliminaire représente les premières phases du cycle de conception ou le produit est en cours de définition. Le nombre d incertitudes sur les paramètres et les informations produit sont très importantes. Il y a un manque de connaissances important à cette étape du processus de conception qui doit être considéré afin d améliorer et d aider les prises de décisions dans les phases amonts. C est ce manque de connaissances que je me propose de qualifier et caractériser en apportant une réponse à la question résultante: comment prendre en compte le manque de connaissances pour prendre des décisions durant la conception préliminaire collaborative ? Pour se faire, nous proposons un méta-modèle de connaissances permettant de structurer les informations du produit et les connaissances en intégrant la maturité du produit. Cette maturité est définie par une métrique et permet d identifier le niveau de connaissances des concepteurs sur le produit et d orienter la prise de décision grâce à l utilisation d une approche mixte, à la fois qualitative et quantitative. Enfin, nous évaluerons la capacité de ce méta-modèle à générer différent modèles produit, puis sa pertinence avec l implémentation sur un cas industriel.The design of mechanical systems, due to their multi-disciplinary and technological aspects, involves different people who, together, work and make decisions and jointly participate in the development of the product. They work in a collaborative manner; however, they may have different strategies, geographical positions, cultures and do not know the other members of the team. Preliminary design represents the early stages of the design cycle or product definition. A number of uncertainties regarding the parameters and product information are very important. There is an important lack of knowledge at this stage of the design process that must be managed or filled in order to improve and support the decision making in the early phases. It is this lack of knowledge that I propose to qualify and characterise, providing an answer to the question: how does one to take into account the lack of knowledge in decision making during the preliminary design collaboration? To do so, we propose a meta-model for structuring product information and knowledge by integrating product maturity. A metric allows this maturity to be defined, to identify the level of knowledge of the product designers and to guide the decision making, thanks to the use of a qualitative and quantitative approach. Finally, we evaluate the ability of the meta-model to generate the different models produced and its relevance to the implementation in an industrial case.COMPIEGNE-BU (601592101) / SudocSudocFranceF

Dyonic Non-Abelian Black Holes

We study static spherically symmetric dyonic black holes in Einstein-Yang-Mills-Higgs theory. As for the magnetic non-abelian black holes, the domain of existence of the dyonic non-abelian black holes is limited with respect to the horizon radius and the dimensionless coupling constant $\alpha$, which is proportional to the ratio of vector meson mass and Planck mass. At a certain critical value of this coupling constant, $\hat \alpha$, the maximal horizon radius is attained. We derive analytically a relation between $\hat \alpha$ and the charge of the black hole solutions and confirm this relation numerically. Besides the fundamental dyonic non-abelian black holes, we study radially excited dyonic non-abelian black holes and globally regular gravitating dyons.Comment: LaTeX, 22 pages, 16 figures, three figures added, file manipulation error in previous replac

Heterosubtype Neutralizing Responses to Influenza A (H5N1) Viruses Are Mediated by Antibodies to Virus Haemagglutinin

Background: It is increasingly clear that influenza A infection induces cross-subtype neutralizing antibodies that may potentially confer protection against zoonotic infections. It is unclear whether this is mediated by antibodies to the neuraminidase (NA) or haemagglutinin (HA). We use pseudoviral particles (H5pp) coated with H5 haemagglutinin but not N1 neuraminidase to address this question. In this study, we investigate whether cross-neutralizing antibodies in persons unexposed to H5N1 is reactive to the H5 haemagglutinin. Methodology/Principal Findings: We measured H5-neutralization antibody titers pre- and post-vaccination using the H5N1 micro-neutralization test (MN) and H5pp tests in subjects given seasonal vaccines and in selected sera from European elderly volunteers in a H5N1 vaccine trial who had detectable pre-vaccination H5N1 MN antibody titers. We found detectable (titer ≥20) H5N1 neutralizing antibodies in a minority of pre-seasonal vaccine sera and evidence of a serological response to H5N1 in others after seasonal influenza vaccination. There was excellent correlation in the antibody titers between the H5N1 MN and H5pp tests. Similar correlations were found between MN and H5pp in the pre-vaccine sera from the cohort of H5N1 vaccine trial recipients. Conclusions/Significance: Heterosubtype neutralizing antibody to H5N1 in healthy volunteers unexposed to H5N1 is mediated by cross-reaction to the H5 haemagglutinin. Copyright: © 2009 Garcia et al.published_or_final_versio

The catalytic subunit of the system L1 amino acid transporter (S<i>lc7a5</i>) facilitates nutrient signalling in mouse skeletal muscle

The System L1-type amino acid transporter mediates transport of large neutral amino acids (LNAA) in many mammalian cell-types. LNAA such as leucine are required for full activation of the mTOR-S6K signalling pathway promoting protein synthesis and cell growth. The SLC7A5 (LAT1) catalytic subunit of high-affinity System L1 functions as a glycoprotein-associated heterodimer with the multifunctional protein SLC3A2 (CD98). We generated a floxed Slc7a5 mouse strain which, when crossed with mice expressing Cre driven by a global promoter, produced Slc7a5 heterozygous knockout (Slc7a5+/-) animals with no overt phenotype, although homozygous global knockout of Slc7a5 was embryonically lethal. Muscle-specific (MCK Cre-mediated) Slc7a5 knockout (MS-Slc7a5-KO) mice were used to study the role of intracellular LNAA delivery by the SLC7A5 transporter for mTOR-S6K pathway activation in skeletal muscle. Activation of muscle mTOR-S6K (Thr389 phosphorylation) in vivo by intraperitoneal leucine injection was blunted in homozygous MS-Slc7a5-KO mice relative to wild-type animals. Dietary intake and growth rate were similar for MS-Slc7a5-KO mice and wild-type littermates fed for 10 weeks (to age 120 days) with diets containing 10%, 20% or 30% of protein. In MS-Slc7a5-KO mice, Leu and Ile concentrations in gastrocnemius muscle were reduced by ∼40% as dietary protein content was reduced from 30 to 10%. These changes were associated with >50% decrease in S6K Thr389 phosphorylation in muscles from MS-Slc7a5-KO mice, indicating reduced mTOR-S6K pathway activation, despite no significant differences in lean tissue mass between groups on the same diet. MS-Slc7a5-KO mice on 30% protein diet exhibited mild insulin resistance (e.g. reduced glucose clearance, larger gonadal adipose depots) relative to control animals. Thus, SLC7A5 modulates LNAA-dependent muscle mTOR-S6K signalling in mice, although it appears non-essential (or is sufficiently compensated by e.g. SLC7A8 (LAT2)) for maintenance of normal muscle mass

High precision astrometry mission for the detection and characterization of nearby habitable planetary systems with the Nearby Earth Astrometric Telescope (NEAT)

(abridged) A complete census of planetary systems around a volume-limited sample of solar-type stars (FGK dwarfs) in the Solar neighborhood with uniform sensitivity down to Earth-mass planets within their Habitable Zones out to several AUs would be a major milestone in extrasolar planets astrophysics. This fundamental goal can be achieved with a mission concept such as NEAT - the Nearby Earth Astrometric Telescope. NEAT is designed to carry out space-borne extremely-high-precision astrometric measurements sufficient to detect dynamical effects due to orbiting planets of mass even lower than Earth's around the nearest stars. Such a survey mission would provide the actual planetary masses and the full orbital geometry for all the components of the detected planetary systems down to the Earth-mass limit. The NEAT performance limits can be achieved by carrying out differential astrometry between the targets and a set of suitable reference stars in the field. The NEAT instrument design consists of an off-axis parabola single-mirror telescope, a detector with a large field of view made of small movable CCDs located around a fixed central CCD, and an interferometric calibration system originating from metrology fibers located at the primary mirror. The proposed mission architecture relies on the use of two satellites operating at L2 for 5 years, flying in formation and offering a capability of more than 20,000 reconfigurations (alternative option uses deployable boom). The NEAT primary science program will encompass an astrometric survey of our 200 closest F-, G- and K-type stellar neighbors, with an average of 50 visits. The remaining time might be allocated to improve the characterization of the architecture of selected planetary systems around nearby targets of specific interest (low-mass stars, young stars, etc.) discovered by Gaia, ground-based high-precision radial-velocity surveys.Comment: Accepted for publication in Experimental Astronomy. The full member list of the NEAT proposal and the news about the project are available at http://neat.obs.ujf-grenoble.fr. The final publication is available at http://www.springerlink.co

Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma

<p>Abstract</p> <p>Background</p> <p>Several single center studies have provided evidence of immune activation and antitumor activity of therapeutic vaccination with dendritic cells (DC) in patients with metastatic melanoma. The efficacy of this approach in patients with favorable prognosis metastatic melanoma limited to the skin, subcutaneous tissues and lung (stages IIIc, M1a, M1b) was tested in a multicenter two stage phase 2 study with centralized DC manufacturing.</p> <p>Methods</p> <p>The vaccine (IDD-3) consisted 8 doses of autologous monocyte-derived matured DC generated in serum-free medium with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-13 (IL-13), pulsed with lysates of three allogeneic melanoma cell lines, and matured with interferon gamma. The primary endpoint was antitumor activity.</p> <p>Results</p> <p>Among 33 patients who received IDD-3 there was one complete response (CR), two partial responses (PR), and six patients had stable disease (SD) lasting more than eight weeks. The overall prospectively defined tumor growth control rate was 27% (90% confidence interval of 13-46%). IDD-3 administration had minimal toxicity and it resulted in a high frequency of immune activation to immunizing melanoma antigens as assessed by <it>in vitro </it>immune monitoring assays.</p> <p>Conclusions</p> <p>The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma.</p> <p>Clinical trial registration</p> <p>NCT00107159.</p

The First Cellular Models Based on Frataxin Missense Mutations That Reproduce Spontaneously the Defects Associated with Friedreich Ataxia

BACKGROUND:Friedreich ataxia (FRDA), the most common form of recessive ataxia, is due to reduced levels of frataxin, a highly conserved mitochondrial iron-chaperone involved in iron-sulfur cluster (ISC) biogenesis. Most patients are homozygous for a (GAA)(n) expansion within the first intron of the frataxin gene. A few patients, either with typical or atypical clinical presentation, are compound heterozygous for the GAA expansion and a micromutation. METHODOLOGY:We have developed a new strategy to generate murine cellular models for FRDA: cell lines carrying a frataxin conditional allele were used in combination with an EGFP-Cre recombinase to create murine cellular models depleted for endogenous frataxin and expressing missense-mutated human frataxin. We showed that complete absence of murine frataxin in fibroblasts inhibits cell division and leads to cell death. This lethal phenotype was rescued through transgenic expression of human wild type as well as mutant (hFXN(G130V) and hFXN(I154F)) frataxin. Interestingly, cells expressing the mutated frataxin presented a FRDA-like biochemical phenotype. Though both mutations affected mitochondrial ISC enzymes activities and mitochondria ultrastructure, the hFXN(I154F) mutant presented a more severe phenotype with affected cytosolic and nuclear ISC enzyme activities, mitochondrial iron accumulation and an increased sensitivity to oxidative stress. The differential phenotype correlates with disease severity observed in FRDA patients. CONCLUSIONS:These new cellular models, which are the first to spontaneously reproduce all the biochemical phenotypes associated with FRDA, are important tools to gain new insights into the in vivo consequences of pathological missense mutations as well as for large-scale pharmacological screening aimed at compensating frataxin deficiency

Towards 4th generation biomaterials: a covalent hybrid polymer-ormoglass architecture

Hybrid materials are being extensively investigated with the aim of mimicking the ECM microenvironment to develop effective solutions for bone tissue engineering. However, the common drawbacks of a hybrid material are the lack of interactions between the scaffold's constituents and the masking of its bioactive phase. Conventional hybrids often degrade in a non-homogeneous manner and the biological response is far from optimal. We have developed a novel material with strong interactions between constituents. The bioactive phase is directly exposed on its surface mimicking the structure of the ECM of bone. Here, polylactic acid electrospun fibers have been successfully and reproducibly coated with a bioactive organically modified glass (ormoglass, Si-Ca-P2 system) covalently. In comparison with the pure polymeric mats, the fibers obtained showed improved hydrophilicity and mechanical properties, bioactive ion release, exhibited a nanoroughness and enabled good cell adhesion and spreading after just one day of culture (rMSCs and rEPCs). The fibers were coated with different ormoglass compositions to tailor their surface properties (roughness, stiffness, and morphology) by modifying the experimental parameters. Knowing that cells modulate their behavior according to the exposed physical and chemical signals, the development of this instructive material is a valuable advance in the design of functional regenerative biomaterials