References of "Heirendt, Laurent 50020772"
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See detailSystematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease
Heinken, Almut Katrin UL; Ravcheev, Dmitry UL; Baldini, Federico UL et al

in Microbiome (2019)

Background The human gut microbiome performs important functions in human health and disease. A classic example for host-gut microbial co-metabolism is host biosynthesis of primary bile acids and their ... [more ▼]

Background The human gut microbiome performs important functions in human health and disease. A classic example for host-gut microbial co-metabolism is host biosynthesis of primary bile acids and their subsequent deconjugation and transformation by the gut microbiome. To understand these system-level host-microbe interactions, a mechanistic, multi-scale computational systems biology approach that integrates the different types of omic data is needed. Here, we use a systematic workflow to computationally model bile acid metabolism in gut microbes and microbial communities. Results Therefore, we first performed a comparative genomic analysis of bile acid deconjugation and biotransformation pathways in 693 human gut microbial genomes and expanded 232 curated genome-scale microbial metabolic reconstructions with the corresponding reactions (available at https://vmh.life). We then predicted the bile acid biotransformation potential of each microbe and in combination with other microbes. We found that each microbe could produce maximally six of the 13 secondary bile acids in silico, while microbial pairs could produce up to 12 bile acids, suggesting bile acid biotransformation being a microbial community task. To investigate the metabolic potential of a given microbiome, publicly available metagenomics data from healthy Western individuals, as well as inflammatory bowel disease patients and healthy controls, were mapped onto the genomes of the reconstructed strains. We constructed for each individual a large-scale personalized microbial community model that takes into account strain-level abundances. Using flux balance analysis, we found considerable variation in the potential to deconjugate and transform primary bile acids between the gut microbiomes of healthy individuals. Moreover, the microbiomes of pediatric inflammatory bowel disease patients were significantly depleted in their bile acid production potential compared with that of controls. The contributions of each strain to overall bile acid production potential across individuals were found to be distinct between inflammatory bowel disease patients and controls. Finally, bottlenecks limiting secondary bile acid production potential were identified in each microbiome model. Conclusions This large-scale modeling approach provides a novel way of analyzing metagenomics data to accelerate our understanding of the metabolic interactions between the host and gut microbiomes in health and diseases states. Our models and tools are freely available to the scientific community. [less ▲]

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See detailCreation and analysis of biochemical constraint-based models using the COBRA Toolbox v.3.0.
Heirendt, Laurent UL; Arreckx, Sylvain; Pfau, Thomas UL et al

in Nature protocols (2019), 14(3), 639-702

Constraint-based reconstruction and analysis (COBRA) provides a molecular mechanistic framework for integrative analysis of experimental molecular systems biology data and quantitative prediction of ... [more ▼]

Constraint-based reconstruction and analysis (COBRA) provides a molecular mechanistic framework for integrative analysis of experimental molecular systems biology data and quantitative prediction of physicochemically and biochemically feasible phenotypic states. The COBRA Toolbox is a comprehensive desktop software suite of interoperable COBRA methods. It has found widespread application in biology, biomedicine, and biotechnology because its functions can be flexibly combined to implement tailored COBRA protocols for any biochemical network. This protocol is an update to the COBRA Toolbox v.1.0 and v.2.0. Version 3.0 includes new methods for quality-controlled reconstruction, modeling, topological analysis, strain and experimental design, and network visualization, as well as network integration of chemoinformatic, metabolomic, transcriptomic, proteomic, and thermochemical data. New multi-lingual code integration also enables an expansion in COBRA application scope via high-precision, high-performance, and nonlinear numerical optimization solvers for multi-scale, multi-cellular, and reaction kinetic modeling, respectively. This protocol provides an overview of all these new features and can be adapted to generate and analyze constraint-based models in a wide variety of scenarios. The COBRA Toolbox v.3.0 provides an unparalleled depth of COBRA methods. [less ▲]

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See detailLubrication mechanism design for aircraft landing gear bearings
Heirendt, Laurent UL; Hugh, Hugh H.T.; Wang, Phillip

Patent (2018)

A shock absorber with lubricated bearings for an aircraft landing gear includes a piston that is received in a cylinder, and an upper bearing fixed to the piston that slidably engages an inner surface of ... [more ▼]

A shock absorber with lubricated bearings for an aircraft landing gear includes a piston that is received in a cylinder, and an upper bearing fixed to the piston that slidably engages an inner surface of the cylinder. A lower bearing extends inwardly from a lower portion of the cylinder and engages an outer surface of the piston. The lower bearing has a center axis and defines an annular bearing surface configured to slidably engage the piston outer surface. The annular bearing surface has a first portion that extends circumferentially more than one hundred eighty degrees about the center axis at a constant radius, defining a circular annular segment. A second portion closes the circular annular segment and defines a shallow channel or pocket in the annular bearing surface. In some embodiments the lower bearing further comprises oppositely disposed frustoconical thrust portions. [less ▲]

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See detailThe Microbiome Modeling Toolbox: from microbial interactions to personalized microbial communities
Baldini, Federico UL; Heinken, Almut Katrin UL; Heirendt, Laurent UL et al

in Bioinformatics (2018)

The application of constraint-based modeling to functionally analyze metagenomic data has been limited so far, partially due to the absence of suitable toolboxes. To address this gap, we created a ... [more ▼]

The application of constraint-based modeling to functionally analyze metagenomic data has been limited so far, partially due to the absence of suitable toolboxes. To address this gap, we created a comprehensive toolbox to model i) microbe-microbe and host-microbe metabolic interactions, and ii) microbial communities using microbial genome-scale metabolic reconstructions and metagenomic data. The Microbiome Modeling Toolbox extends the functionality of the COBRA Toolbox. The Microbiome Modeling Toolbox and the tutorials at https://git.io/microbiomeModelingToolbox. [less ▲]

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See detailThe Virtual Metabolic Human database: integrating human and gut microbiome metabolism with nutrition and disease
Noronha, Alberto UL; Modamio Chamarro, Jennifer UL; Jarosz, Yohan UL et al

in Nucleic Acids Research (2018)

A multitude of factors contribute to complex diseases and can be measured with ‘omics’ methods. Databases facilitate data interpretation for underlying mechanisms. Here, we describe the Virtual Metabolic ... [more ▼]

A multitude of factors contribute to complex diseases and can be measured with ‘omics’ methods. Databases facilitate data interpretation for underlying mechanisms. Here, we describe the Virtual Metabolic Human (VMH, www.vmh.life) database encapsulating current knowledge of human metabolism within five interlinked resources ‘Human metabolism’, ‘Gut microbiome’, ‘Disease’, ‘Nutrition’, and ‘ReconMaps’. The VMH captures 5180 unique metabolites, 17 730 unique reactions, 3695 human genes, 255 Mendelian diseases, 818 microbes, 632 685 microbial genes and 8790 food items. The VMH’s unique features are (i) the hosting of the metabolic reconstructions of human and gut microbes amenable for metabolic modeling; (ii) seven human metabolic maps for data visualization; (iii) a nutrition designer; (iv) a user-friendly webpage and application-programming interface to access its content; (v) user feedback option for community engagement and (vi) the connection of its entities to 57 other web resources. The VMH represents a novel, interdisciplinary database for data interpretation and hypothesis generation to the biomedical community. [less ▲]

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See detailDistributedFBA.jl: High-level, high-performance flux balance analysis in Julia.
Heirendt, Laurent UL; Thiele, Ines UL; Fleming, Ronan MT UL

in Bioinformatics (2017)

MOTIVATION: Flux balance analysis, and its variants, are widely used methods for predicting steady-state reaction rates in biochemical reaction networks. The exploration of high dimensional networks with ... [more ▼]

MOTIVATION: Flux balance analysis, and its variants, are widely used methods for predicting steady-state reaction rates in biochemical reaction networks. The exploration of high dimensional networks with such methods is currently hampered by software performance limitations. RESULTS: DistributedFBA.jl is a high-level, high-performance, open-source implementation of flux balance analysis in Julia. It is tailored to solve multiple flux balance analyses on a subset or all the reactions of large and huge-scale networks, on any number of threads or nodes. AVAILABILITY: The code is freely available on github.com/opencobra/COBRA.jl. The documentation can be found at opencobra.github.io/COBRA.jl. [less ▲]

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See detailAircraft landing gear thermo-tribomechanical model development
Heirendt, Laurent UL

Doctoral thesis (2015)

A transient numerical model for studying the thermo-tribomechanical behavior of an aircraft landing gear is presented. The study reveals the major heat sources and heat sinks that impact the ... [more ▼]

A transient numerical model for studying the thermo-tribomechanical behavior of an aircraft landing gear is presented. The study reveals the major heat sources and heat sinks that impact the characteristic thermal behavior of the landing gear shock absorber. The severe in-service performance degradation and reported structural damage can be explained as a consequence of the heat generated by the high drag loads induced by rough runways on the bearings, and by the high sliding velocities of the piston. A conclusive model may lead to improved landing gear performance once the transient process of heat generation in a phase-changing grease-lubricated lower bearing is fundamentally understood. A novel tribotopological lubrication theory is derived in order to take into account all distinct physical phases of the non-Newtonian Bingham lubricant. The governing equations are solved using a hybrid numerical solver that is optimized for numerical efficiency and fast convergence. The proposed framework is validated against existing theories and results, and it demonstrates accurate predictions of the thermal performance of the landing gear. Strategies to passively optimize the lower bearing lubrication mechanism are further suggested in order to achieve optimal thermal performance of future aircraft landing gear. [less ▲]

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See detailAircraft landing gear greased slider bearing steady-state thermo-elastohydrodynamic concept model
Heirendt, Laurent UL; Hugh, Liu; Wang, Phillip

in Tribology International (2015), 82(B), 453-463

This paper presents a steady-state concept model for studying the thermal behavior of a greased aircraft landing gear lower slider bearing. Structural damage has been reported as a consequence of ... [more ▼]

This paper presents a steady-state concept model for studying the thermal behavior of a greased aircraft landing gear lower slider bearing. Structural damage has been reported as a consequence of excessive heat generated by the high loads induced by rough runways on the bearings, and by the high sliding velocities of the piston. The goal of the model is to enable fundamental understanding of the frictional heat generation. The governing equations are adapted for grease flow and special attention is given to the underlying algorithm of the developed numerical framework used to efficiently solve the governing equations. The developed numerical code is validated against existing results. Numerical results indicate fundamental differences in fluid flow behavior between greased and oil-lubricated bearings. [less ▲]

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See detailAircraft Landing Gear Thermo-Tribomechanical Model and Sensitivity Study
Heirendt, Laurent UL; Wang, Phillip; Liu, Hugh H.T.

in Journal of Aircraft (2014), 51(2), 511-519

A methodology for characterizing the thermo-tribomechanical response of an aircraft landing gear shock absorber is presented. Structural damage has been reported as a consequence of heat generated by high ... [more ▼]

A methodology for characterizing the thermo-tribomechanical response of an aircraft landing gear shock absorber is presented. Structural damage has been reported as a consequence of heat generated by high loads induced by rough runways on the shock absorber bearings and by the high sliding velocities of the shock absorber piston. Therefore, a model that reveals the characteristics of the thermal behavior, and identifies heat sources and sinks in the landing gear shock absorber is developed. The thermo-tribomechanical model framework is presented with representative development of each component. In addition, a sensitivity study of the maximum heat flux to variations of key input parameters is investigated. The numerical results indicate that the runway amplitude dominates the landing gear thermal response. [less ▲]

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