Academic literature on the topic 'Synthèse de pipeline'

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Journal articles on the topic "Synthèse de pipeline"

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Gintjee, Thomas J., Monica A. Donnelley, and George R. Thompson. "Aspiring Antifungals: Review of Current Antifungal Pipeline Developments." Journal of Fungi 6, no. 1 (February 25, 2020): 28. http://dx.doi.org/10.3390/jof6010028.

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Invasive fungal infections are associated with significant morbidity and mortality, and their management is restricted to a variety of agents from five established classes of antifungal medication. In practice, existing antifungal agents are often constrained by dose-limiting toxicities, drug interactions, and the routes of administration. An increasing prevalence of invasive fungal infections along with rising rates of resistance and the practical limitations of existing agents has created a demand for the development of new antifungals, particularly those with novel mechanisms of action. This article reviews antifungal agents currently in various stages of clinical development. New additions to existing antifungal classes will be discussed, including SUBA-itraconazole, a highly bioavailable azole, and amphotericin B cochleate, an oral amphotericin formulation, as well as rezafungin, a long-acting echinocandin capable of once-weekly administration. Additionally, novel first-in-class agents such as ibrexafungerp, an oral glucan synthase inhibitor with activity against various resistant fungal isolates, and olorofim, a pyrimidine synthesis inhibitor with a broad spectrum of activity and oral formulation, will be reviewed. Various other innovative antifungal agents and classes, including MGCD290, tetrazoles, and fosmanogepix, will also be examined.
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Blin, Kai, Simon Shaw, Katharina Steinke, Rasmus Villebro, Nadine Ziemert, Sang Yup Lee, Marnix H. Medema, and Tilmann Weber. "antiSMASH 5.0: updates to the secondary metabolite genome mining pipeline." Nucleic Acids Research 47, W1 (April 29, 2019): W81—W87. http://dx.doi.org/10.1093/nar/gkz310.

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Abstract Secondary metabolites produced by bacteria and fungi are an important source of antimicrobials and other bioactive compounds. In recent years, genome mining has seen broad applications in identifying and characterizing new compounds as well as in metabolic engineering. Since 2011, the ‘antibiotics and secondary metabolite analysis shell—antiSMASH’ (https://antismash.secondarymetabolites.org) has assisted researchers in this, both as a web server and a standalone tool. It has established itself as the most widely used tool for identifying and analysing biosynthetic gene clusters (BGCs) in bacterial and fungal genome sequences. Here, we present an entirely redesigned and extended version 5 of antiSMASH. antiSMASH 5 adds detection rules for clusters encoding the biosynthesis of acyl-amino acids, β-lactones, fungal RiPPs, RaS-RiPPs, polybrominated diphenyl ethers, C-nucleosides, PPY-like ketones and lipolanthines. For type II polyketide synthase-encoding gene clusters, antiSMASH 5 now offers more detailed predictions. The HTML output visualization has been redesigned to improve the navigation and visual representation of annotations. We have again improved the runtime of analysis steps, making it possible to deliver comprehensive annotations for bacterial genomes within a few minutes. A new output file in the standard JavaScript object notation (JSON) format is aimed at downstream tools that process antiSMASH results programmatically.
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Van Daele, Ruth, Isabel Spriet, Joost Wauters, Johan Maertens, Toine Mercier, Sam Van Hecke, and Roger Brüggemann. "Antifungal drugs: What brings the future?" Medical Mycology 57, Supplement_3 (June 1, 2019): S328—S343. http://dx.doi.org/10.1093/mmy/myz012.

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AbstractThe high burden and growing prevalence of invasive fungal infections (IFIs), the toxicity and interactions associated with current antifungal drugs, as well as the increasing resistance, ask for the development of new antifungal drugs, preferably with a novel mode of action. Also, the availability of oral or once-weekly alternatives would enable ambulatory treatment resulting in an improved patient's comfort and therapy adherence. However, only one new azole and two new posaconazole-formulations were marketed over the last decade. This review focuses on the antifungal drugs in the pipeline undergoing clinical evaluation. First, the newest azole, isavuconazole, with its improved safety profile and reduction in DDIs, will be discussed. Moreover, there are two glucan synthase inhibitors (GSIs) in the antifungal pipeline: rezafungin (CD101), a long-acting echinocandin with an improved stability that enables once weekly administration, and SCY-078, an orally available GSI with efficacy against azole- and echinocandin resistant isolates. A new oral formulation of amphotericin B will also be presented. Moreover, the first representative of a new antifungal class, the orotomides, with a broad spectrum and no cross-resistance with current antifungal classes, will be discussed. Finally, an overview of other antifungals that are still in earlier clinical development phases, is provided.
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Gastaldelli, Amalia, Norbert Stefan, and Hans-Ulrich Häring. "Liver-targeting drugs and their effect on blood glucose and hepatic lipids." Diabetologia 64, no. 7 (April 20, 2021): 1461–79. http://dx.doi.org/10.1007/s00125-021-05442-2.

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AbstractThe global epidemic of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) and the high prevalence among individuals with type 2 diabetes has attracted the attention of clinicians specialising in liver disorders. Many drugs are in the pipeline for the treatment of NAFLD/NASH, and several glucose-lowering drugs are now being tested specifically for the treatment of liver disease. Among these are nuclear hormone receptor agonists (e.g. peroxisome proliferator-activated receptor agonists, farnesoid X receptor agonists and liver X receptor agonists), fibroblast growth factor-19 and -21, single, dual or triple incretins, sodium–glucose cotransporter inhibitors, drugs that modulate lipid or other metabolic pathways (e.g. inhibitors of fatty acid synthase, diacylglycerol acyltransferase-1, acetyl-CoA carboxylase and 11β-hydroxysteroid dehydrogenase type-1) or drugs that target the mitochondrial pyruvate carrier. We have reviewed the metabolic effects of these drugs in relation to improvement of diabetic hyperglycaemia and fatty liver disease, as well as peripheral metabolism and insulin resistance. Graphical abstract
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Joppe, Mirko, Edoardo D'Imprima, Nina Salustros, Karthik S. Paithankar, Janet Vonck, Martin Grininger, and Werner Kühlbrandt. "The resolution revolution in cryoEM requires high-quality sample preparation: a rapid pipeline to a high-resolution map of yeast fatty acid synthase." IUCrJ 7, no. 2 (January 25, 2020): 220–27. http://dx.doi.org/10.1107/s2052252519017366.

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Single-particle electron cryo-microscopy (cryoEM) has undergone a `resolution revolution' that makes it possible to characterize megadalton (MDa) complexes at atomic resolution without crystals. To fully exploit the new opportunities in molecular microscopy, new procedures for the cloning, expression and purification of macromolecular complexes need to be explored. Macromolecular assemblies are often unstable, and invasive construct design or inadequate purification conditions and sample-preparation methods can result in disassembly or denaturation. The structure of the 2.6 MDa yeast fatty acid synthase (FAS) has been studied by electron microscopy since the 1960s. Here, a new, streamlined protocol for the rapid production of purified yeast FAS for structure determination by high-resolution cryoEM is reported. Together with a companion protocol for preparing cryoEM specimens on a hydrophilized graphene layer, the new protocol yielded a 3.1 Å resolution map of yeast FAS from 15 000 automatically picked particles within a day. The high map quality enabled a complete atomic model of an intact fungal FAS to be built.
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Leber, Christopher A., C. Benjamin Naman, Lena Keller, Jehad Almaliti, Eduardo J. E. Caro-Diaz, Evgenia Glukhov, Valsamma Joseph, et al. "Applying a Chemogeographic Strategy for Natural Product Discovery from the Marine Cyanobacterium Moorena bouillonii." Marine Drugs 18, no. 10 (October 14, 2020): 515. http://dx.doi.org/10.3390/md18100515.

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The tropical marine cyanobacterium Moorena bouillonii occupies a large geographic range across the Indian and Western Tropical Pacific Oceans and is a prolific producer of structurally unique and biologically active natural products. An ensemble of computational approaches, including the creation of the ORCA (Objective Relational Comparative Analysis) pipeline for flexible MS1 feature detection and multivariate analyses, were used to analyze various M. bouillonii samples. The observed chemogeographic patterns suggested the production of regionally specific natural products by M. bouillonii. Analyzing the drivers of these chemogeographic patterns allowed for the identification, targeted isolation, and structure elucidation of a regionally specific natural product, doscadenamide A (1). Analyses of MS2 fragmentation patterns further revealed this natural product to be part of an extensive family of herein annotated, proposed natural structural analogs (doscadenamides B–J, 2–10); the ensemble of structures reflect a combinatorial biosynthesis using nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) components. Compound 1 displayed synergistic in vitro cancer cell cytotoxicity when administered with lipopolysaccharide (LPS). These discoveries illustrate the utility in leveraging chemogeographic patterns for prioritizing natural product discovery efforts.
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Freudenberg, Robert A., Luisa Wittemeier, Alexander Einhaus, Thomas Baier, and Olaf Kruse. "The Spermidine Synthase Gene SPD1: A Novel Auxotrophic Marker for Chlamydomonas reinhardtii Designed by Enhanced CRISPR/Cas9 Gene Editing." Cells 11, no. 5 (February 28, 2022): 837. http://dx.doi.org/10.3390/cells11050837.

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Biotechnological application of the green microalga Chlamydomonas reinhardtii hinges on the availability of selectable markers for effective expression of multiple transgenes. However, biological safety concerns limit the establishment of new antibiotic resistance genes and until today, only a few auxotrophic markers exist for C. reinhardtii. The recent improvements in gene editing via CRISPR/Cas allow directed exploration of new endogenous selectable markers. Since editing frequencies remain comparably low, a Cas9-sgRNA ribonucleoprotein (RNP) delivery protocol was strategically optimized by applying nitrogen starvation to the pre-culture, which improved successful gene edits from 10% to 66% after pre-selection. Probing the essential polyamine biosynthesis pathway, the spermidine synthase gene (SPD1) is shown to be a potent selectable marker with versatile biotechnological applicability. Very low levels of spermidine (0.75 mg/L) were required to maintain normal mixotrophic and phototrophic growth in newly designed spermidine auxotrophic strains. Complementation of these strains with a synthetic SPD1 gene was achieved when the mature protein was expressed in the cytosol or targeted to the chloroplast. This work highlights the potential of new selectable markers for biotechnology as well as basic research and proposes an effective pipeline for the identification of new auxotrophies in C. reinhardtii.
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Rehman, Abdur, Sajjad Ahmad, Farah Shahid, Aqel Albutti, Ameen S. S. Alwashmi, Mohammad Abdullah Aljasir, Naif Alhumeed, Muhammad Qasim, Usman Ali Ashfaq, and Muhammad Tahir ul Qamar. "Integrated Core Proteomics, Subtractive Proteomics, and Immunoinformatics Investigation to Unveil a Potential Multi-Epitope Vaccine against Schistosomiasis." Vaccines 9, no. 6 (June 16, 2021): 658. http://dx.doi.org/10.3390/vaccines9060658.

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Schistosomiasis is a parasitic infection that causes considerable morbidity and mortality in the world. Infections of parasitic blood flukes, known as schistosomes, cause the disease. No vaccine is available yet and thus there is a need to design an effective vaccine against schistosomiasis. Schistosoma japonicum, Schistosoma mansoni, and Schistosoma haematobium are the main pathogenic species that infect humans. In this research, core proteomics was combined with a subtractive proteomics pipeline to identify suitable antigenic proteins for the construction of a multi-epitope vaccine (MEV) against human-infecting Schistosoma species. The pipeline revealed two antigenic proteins—calcium binding and mycosubtilin synthase subunit C—as promising vaccine targets. T and B cell epitopes from the targeted proteins were predicted using multiple bioinformatics and immunoinformatics databases. Seven cytotoxic T cell lymphocytes (CTL), three helper T cell lymphocytes (HTL), and four linear B cell lymphocytes (LBL) epitopes were fused with a suitable adjuvant and linkers to design a 217 amino-acid-long MEV. The vaccine was coupled with a TLR-4 agonist (RS-09; Sequence: APPHALS) adjuvant to enhance the immune responses. The designed MEV was stable, highly antigenic, and non-allergenic to human use. Molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MMGBSA) analysis were performed to study the binding affinity and molecular interactions of the MEV with human immune receptors (TLR2 and TLR4) and MHC molecules (MHC I and MHC II). The MEV expression capability was tested in an Escherichia coli (strain-K12) plasmid vector pET-28a(+). Findings of these computer assays proved the MEV as highly promising in establishing protective immunity against the pathogens; nevertheless, additional validation by in vivo and in vitro experiments is required to discuss its real immune-protective efficacy.
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Randhawa, Gurinder Jit, Ruchi Sharma, and Monika Singh. "Qualitative and Event-Specific Real-Time PCR Detection Methods for Bt Brinjal Event EE-1." Journal of AOAC INTERNATIONAL 95, no. 6 (November 1, 2012): 1733–39. http://dx.doi.org/10.5740/jaoacint.11-478.

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Abstract Bt brinjal event EE-1 with cry1Ac gene, expressing insecticidal protein against fruit and shoot borer, is the first genetically modified food crop in the pipeline for commercialization in India. Qualitative polymerase chain reaction (PCR) along with event-specific conventional as well as real-time PCR methods to characterize the event EE-1 is reported. A multiplex (pentaplex) PCR system simultaneously amplifying cry1Ac transgene, Cauliflower Mosaic Virus (CaMV) 35S promoter, nopaline synthase (nos) terminator, aminoglycoside adenyltransferase (aadA) marker gene, and a taxon-specific β-fructosidase gene in event EE-1 has been developed. Furthermore, construct-specific PCR, targeting the approximate 1.8 kb region of inserted gene construct comprising the region of CaMV 35S promoter and cry1Ac gene has also been developed. The LOD of developed EE-1 specific conventional PCR assay is 0.01%. The method performance of the reported real-time PCR assay was consistent with the acceptance criteria of Codex Alimentarius Commission ALINORM 10/33/23, with the LOD and LOQ values of 0.05%. The developed detection methods would not only facilitate effective regulatory compliance for identification of genetic traits, risk assessment, management, and postrelease monitoring, but also address consumer concerns and resolution of legal disputes.
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Juhás, Martin, Andrea Bachtíková, Daria Elżbieta Nawrot, Paulína Hatoková, Vinod Sukanth Kumar Pallabothula, Adéla Diepoltová, Ondřej Janďourek, et al. "Improving Antimicrobial Activity and Physico-Chemical Properties by Isosteric Replacement of 2-Aminothiazole with 2-Aminooxazole." Pharmaceuticals 15, no. 5 (May 6, 2022): 580. http://dx.doi.org/10.3390/ph15050580.

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Antimicrobial drug resistance is currently one of the most critical health issues. Pathogens resistant to last-resort antibiotics are increasing, and very few effective antibacterial agents have been introduced in recent years. The promising drug candidates are often discontinued in the primary stages of the drug discovery pipeline due to their unspecific reactivity (PAINS), toxicity, insufficient stability, or low water solubility. In this work, we investigated a series of substituted N-oxazolyl- and N-thiazolylcarboxamides of various pyridinecarboxylic acids. Final compounds were tested against several microbial species. In general, oxazole-containing compounds showed high activity against mycobacteria, especially Mycobacterium tuberculosis (best MICH37Ra = 3.13 µg/mL), including the multidrug-resistant strains. Promising activities against various bacterial and fungal strains were also observed. None of the compounds was significantly cytotoxic against the HepG2 cell line. Experimental measurement of lipophilicity parameter log k’w and water solubility (log S) confirmed significantly (typically two orders in logarithmic scale) increased hydrophilicity/water solubility of oxazole derivatives in comparison with their thiazole isosteres. Mycobacterial β-ketoacyl-acyl carrier protein synthase III (FabH) was suggested as a probable target by molecular docking and molecular dynamics simulations.
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Dissertations / Theses on the topic "Synthèse de pipeline"

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Morvan, Antoine. "Utilisation du modèle polyédrique pour la synthèse d'architectures pipelinées." Phd thesis, École normale supérieure de Cachan - ENS Cachan, 2013. http://tel.archives-ouvertes.fr/tel-00913692.

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Grâce aux progrès réalisés dans le domaine des semi-conducteurs, les plateformes matérielles embarquées sont capables de satisfaire les contraintes de performances d'applications de plus en plus complexes. Cette augmentation conduit à une explosion des coûts de conception, ce qui pousse les concepteurs de ces plateformes à utiliser des outils travaillant à des niveaux d'abstraction plus élevés. Aujourd'hui, les outils de synthèse de haut niveau opèrent sur des descriptions C/C++ pour en générer des accélérateurs matériels spécialisés. Ces outils offrent des gains en productivité significatifs par rapport à la génération précédente, qui opérait sur des descriptions structurelles de l'architecture en VHDL ou Verilog. Ces descriptions algorithmiques doivent être retravaillées pour que les outils puissent générer des circuits performants. Pour faciliter cette tâche, une solution consiste à mettre en œuvre une boite à outils pour des transformations source-à-source orientées synthèse de haut niveau. En particulier, cette thèse s'intéresse aux transformations de boucles, avec pour objectif d'améliorer les performances en exposant des boucles parallèles et en améliorant la localité des accès mémoire. En nous appuyant sur une représentation des boucles dans le modèle polyédrique, nous proposons une approche qui améliore l'applicabilité du pipeline de nids de boucles en vérifiant sa légalité de manière plus précise que les approches existantes. De plus, lorsque la vérification échoue, nous proposons une technique de correction qui insère statiquement des états d'attente pour assurer la légalité du pipeline. Enfin, ce pipeline est mis en œuvre en utilisant une technique de génération de code qui met les nids de boucles à plat. Ces contributions ont été implémentées dans l'infrastructure de compilation source-à-source Gecos, avant d'être appliquées à un ensemble de benchmarks représentatifs des noyaux de calculs cibles de la synthèse de haut niveau. Les résultats montrent un gain en performances significatif, avec un surcoût en surface modéré.
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Parrot, Rémi. "Réseaux de Petri temporisés pour la synthèse de circuits pipelinés." Thesis, Ecole centrale de Nantes, 2022. http://www.theses.fr/2022ECDN0048.

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Dans cette thèse, nous nous intéressons à l’optimisation des ressources consommées par un circuit implémentant une loi de commande pour la charge de véhicules électriques sur FPGA. Tout d’abord, nous proposons une nouvelle solution au problème de la synthèse de pipeline minimisant les bascules et garantissant une fréquence minimale de fonctionnement. En se basant sur cette même approche, nous sommes capable de construire un pipeline permettant le pliage (ou multiplexage temporel) du circuit, c’est-à-dire qui permet la fusion de portions du circuit identiques en séquençant leur accès. Ainsi, les ressources consommées sont réduites à la fois en nombre de bascule et en nombre d’unités logiques. Notre approche est basée sur un modèle de Réseau de Petri Temporisé avec des transitions retardables, pouvant rater leur date de tir, et une action spécifique appelée reset qui réinitialise les horloges de toutes les transitions. Ce modèle s’avère équivalent à un automate à une horloge. Une surclasse de ce modèle, les Réseaux de Petri Temporisés avec transitions retardables (sans reset), s’avère être incomparable, en terme d’expressivité en sémantique faible, avec les classes de Réseaux de Petri Temporels ou Temporisés en temps dense ou discret. Enfin, une exploration symbolique de ce modèle ainsi que des résultats de complexité théorique et pratique sont étudiés
In this thesis, we are interested in the optimization of the resources consumed by a circuit implementing a control law for the charging of electric vehicles on FPGA. First, we propose a new solution to the pipeline synthesis problem that minimizes the number of flip-flops and guarantees a minimum operating frequency. Based on this same approach, we are able to build a pipeline that allows the folding (or time multiplexing) of the circuit, i.e., that allows the merging of identical circuit portions by sequencing their access. Thus, the consumed resources are reduced both in number of flip-flops and in number of logical units. Our approach is based on a Timed Petri Net model with delayable transitions that can miss their firing date, and a specific action called reset that resets the clocks of all transitions. This model is shown to be equivalent to a one-clock automaton. An overclass of this model, the Timed Petri Nets with delayable transitions (without reset), turns out tobe incomparable, in terms of expressivity in weak semantics, with the classes of Temporal or Timed Petri nets in dense or discrete time. Finally, a symbolic exploration of this model and results on theoretical and practical complexity are studied
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Rahmouni, Maher. "Ordonnancement et optimisations pour la synthèse de haut niveau des circuits de controle." Grenoble INPG, 1997. http://www.theses.fr/1997INPG0028.

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La plupart des algorithmes d'ordonnancement existants dans le domaine de la synthese de haut niveau sont concus pour des applications dominees par les donnees telles que les applications de traitement de signal. Ces algorithmes ont pour objectif de minimiser le cout de la partie operative. Cependant, dans les circuits de commande modernes, les performances de la partie controle dominent la performance globale du circuit. Il est donc necessaire de prendre en compte les caracteristiques de ces applications et de developper un ensemble de techniques qui permettent de minimiser le cout de la partie controle. Cette these presente de nouvelles techniques d'ordonnancement pour differentes architectures de controleur ainsi qu'une etude sur l'interpretation des structures du langage vhdl par la synthese de haut niveau. Les approches developpees se concentrent sur l'optimisation de la surface du controleur et de la performance du circuit. Le principe de ces techniques est d'analyser les differents chemins d'execution de la description comportementale du circuit representee sous forme d'un graphe de flot de controle. Les algorithmes realises ont ete integres dans l'outil de synthese de haut niveau amical. Les resultats montrent leur efficacite sur des exemples reels de circuits domines par le controle.
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Hinrichsen, Holger. "Ein transformativer Ansatz für die Synthese und Verifikation algorithmischer Hardwarebeschreibungen." [S.l. : s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=962731447.

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Pasca, Bogdan Mihai. "Calcul flottant haute performance sur circuits reconfigurables." Phd thesis, Ecole normale supérieure de lyon - ENS LYON, 2011. http://tel.archives-ouvertes.fr/tel-00654121.

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De plus en plus de constructeurs proposent des accélérateurs de calculs à base de circuits reconfigurables FPGA, cette technologie présentant bien plus de souplesse que le microprocesseur. Valoriser cette flexibilité dans le domaine de l'accélération de calcul flottant en utilisant les langages de description de circuits classiques (VHDL ou Verilog) reste toutefois très difficile, voire impossible parfois. Cette thèse a contribué au développement du logiciel FloPoCo, qui offre aux utilisateurs familiers avec VHDL un cadre C++ de description d'opérateurs arithmétiques génériques adapté au calcul reconfigurable. Ce cadre distingue explicitement la fonctionnalité combinatoire d'un opérateur, et la problématique de son pipeline pour une précision, une fréquence et un FPGA cible donnés. Afin de pouvoir utiliser FloPoCo pour concevoir des opérateurs haute performance en virgule flottante, il a fallu d'abord concevoir des blocs de bases optimisés. Nous avons d'abord développé des additionneurs pipelinés autour des lignes de propagation de retenue rapides, puis, à l'aide de techniques de pavages, nous avons conçu de gros multiplieurs, possiblement tronqués, utilisant des petits multiplieurs. L'évaluation de fonctions élémentaires en flottant implique souvent l'évaluation en virgule fixe d'une fonction. Nous présentons un opérateur générique de FloPoCo qui prend en entrée l'expression de la fonction à évaluer, avec ses précisions d'entrée et de sortie, et construit un évaluateur polynomial optimisé de cette fonction. Ce bloc de base a permis de développer des opérateurs en virgule flottante pour la racine carrée et l'exponentielle qui améliorent considérablement l'état de l'art. Nous avons aussi travaillé sur des techniques de compilation avancée pour adapter l'exécution d'un code C aux pipelines flexibles de nos opérateurs. FloPoCo a pu ainsi être utilisé pour implanter sur FPGA des applications complètes.
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Reports on the topic "Synthèse de pipeline"

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Cytryn, Eddie, Mark R. Liles, and Omer Frenkel. Mining multidrug-resistant desert soil bacteria for biocontrol activity and biologically-active compounds. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7598174.bard.

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Control of agro-associated pathogens is becoming increasingly difficult due to increased resistance and mounting restrictions on chemical pesticides and antibiotics. Likewise, in veterinary and human environments, there is increasing resistance of pathogens to currently available antibiotics requiring discovery of novel antibiotic compounds. These drawbacks necessitate discovery and application of microorganisms that can be used as biocontrol agents (BCAs) and the isolation of novel biologically-active compounds. This highly-synergistic one year project implemented an innovative pipeline aimed at detecting BCAs and associated biologically-active compounds, which included: (A) isolation of multidrug-resistant desert soil bacteria and root-associated bacteria from medicinal plants; (B) invitro screening of bacterial isolates against known plant, animal and human pathogens; (C) nextgeneration sequencing of isolates that displayed antagonistic activity against at least one of the model pathogens and (D) in-planta screening of promising BCAs in a model bean-Sclerotiumrolfsii system. The BCA genome data were examined for presence of: i) secondary metabolite encoding genes potentially linked to the anti-pathogenic activity of the isolates; and ii) rhizosphere competence-associated genes, associated with the capacity of microorganisms to successfully inhabit plant roots, and a prerequisite for the success of a soil amended BCA. Altogether, 56 phylogenetically-diverse isolates with bioactivity against bacterial, oomycete and fungal plant pathogens were identified. These strains were sent to Auburn University where bioassays against a panel of animal and human pathogens (including multi-drug resistant pathogenic strains such as A. baumannii 3806) were conducted. Nineteen isolates that showed substantial antagonistic activity against at least one of the screened pathogens were sequenced, assembled and subjected to bioinformatics analyses aimed at identifying secondary metabolite-encoding and rhizosphere competence-associated genes. The genome size of the bacteria ranged from 3.77 to 9.85 Mbp. All of the genomes were characterized by a plethora of secondary metabolite encoding genes including non-ribosomal peptide synthase, polyketidesynthases, lantipeptides, bacteriocins, terpenes and siderophores. While some of these genes were highly similar to documented genes, many were unique and therefore may encode for novel antagonistic compounds. Comparative genomic analysis of root-associated isolates with similar strains not isolated from root environments revealed genes encoding for several rhizospherecompetence- associated traits including urea utilization, chitin degradation, plant cell polymerdegradation, biofilm formation, mechanisms for iron, phosphorus and sulfur acquisition and antibiotic resistance. Our labs are currently writing a continuation of this feasibility study that proposes a unique pipeline for the detection of BCAs and biopesticides that can be used against phytopathogens. It will combine i) metabolomic screening of strains from our collection that contain unique secondary metabolite-encoding genes, in order to isolate novel antimicrobial compounds; ii) model plant-based experiments to assess the antagonistic capacities of selected BCAs toward selected phytopathogens; and iii) an innovative next-generation-sequencing based method to monitor the relative abundance and distribution of selected BCAs in field experiments in order to assess their persistence in natural agro-environments. We believe that this integrated approach will enable development of novel strains and compounds that can be used in large-scale operations.
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