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Claudia López Zazueta, Olivier Bernard, Jean-Luc Gouzé.
AIChE Journal (2019).
ART
Abstract
Metabolic modeling has gained accuracy in the last decades, but the resulting models are of high dimension and difficult to use for control purpose. Here we propose a mathematical approach to reduce high dimensional linearized metabolic models, which relies on time scale separation and the Quasi Steady State Assumption. Contrary to the Flux Balance Analysis assumption that the whole system reaches an equilibrium, our reduced model depends on a small system of differential equations which represents the slow variables dynamics. Moreover, we prove that the concentration of metabolites in Quasi Steady State is one order of magnitude lower than the concentration of metabolites with slow dynamics (under some flux conditions). Also, we propose a minimization strategy to estimate the reduced system parameters. The reduction of a toy network with the method presented here is compared with other approaches. Finally, our reduction technique is applied to an autotrophic microalgae metabolic network.
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Jérôme Grenier, Hubert Bonnefond, Filipa Lopes, Olivier Bernard.
Algal Research - Biomass, Biofuels and Bioproducts (2019).
ART
Abstract
The production of microalgae using biofilm-based processes is becoming popular because of their higher productivity compared to traditional culture systems. Another advantage of microalgal biofilms is the straightforward harvesting procedure achieved by scraping off the biofilm, significantly reducing the energy demand required when concentrating liquid culture. Here, a promising way to grow microalgae is explored, examining a biofilm developed on a moving conveyor belt. Algae are then successively exposed to light and dark periods as the conveyer belt rotates. A lab-scale biofilm-based reactor mimicking the light pattern of the moving system was first used to study the effect of light/dark cycles on a Chlorella autotrophica biofilm. The succession of light and dark phases (in the order of minutes) effectively dilutes the light over a given time period and mitigates over-exposure of light, which can lead to photoinhibition. When the illumination time represents one-third of the cycle period (light dilution factor of 3), the biofilm seems to deal with photoinhibition better than when the biofilm is exposed to permanent illumination. Extrapolations for a rotating conveyer belt in such conditions points out twofold productivity compared to a static biofilm exposed to continuous light. However, when the periods in the dark extend too long, respiration decreases the carbon pool, hindering the benefit of photosynthesis, and a trade-off must be achieved.
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Walid Djema, Olivier Bernard, Laetitia Giraldi.
FOSBE 2019 - 8th IFAC Conference on Foundations of Systems Biology in Engineering (2019).
COMM
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Marjorie Morales, Arnaud Hélias, Olivier Bernard.
Biotechnology for Biofuels (2019).
ART
Abstract
13 Background: Microalgae are 10 to 20 times more productive than the current agricultural biodiesel 14
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Hubert Bonnefond, Yann Lie, Eric Pruvost, Amélie Talec, Olivier Bernard, Antoine Sciandra.
Alg’in Provence - European Workshop (2019).
COMM
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Freddy Guihéneuf, Alex Wakefield, Quentin Girardin, Antoine Sciandra, Olivier Bernard, Christophe Vasseur, Hubert Bonnefond.
AlgaEurope Conference (2019).
COMM
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Brian D. Shoener, Stephanie M. Schramm, Fabrice Béline, Olivier Bernard, Carlos Martínez, Benedek G. Plosz, Spencer Snowling, Jean-Philippe Steyer, Borja Valverde-Pérez, Dorottya Wagner, Jeremy S. Guest.
Water Research X (2019).
ART
Abstract
Microalgal and cyanobacterial resource recovery systems could significantly advance nutrient recovery from wastewater by achieving effluent nitrogen (N) and phosphorus (P) levels below the current limit of technology. The successful implementation of phytoplankton, however, requires the formulation of process models that balance fidelity and simplicity to accurately simulate dynamic performance in response to environmental conditions. This work synthesizes the range of model structures that have been leveraged for algae and cyanobacteria modeling and core model features that are required to enable reliable process modeling in the context of water resource recovery facilities. Results from an extensive literature review of over 300 published phytoplankton models are presented, with particular attention to similarities with and differences from existing strategies to model chemotrophic wastewater treatment processes (e.g., via the Activated Sludge Models, ASMs). Building on published process models, the core requirements of a model structure for algal and cyanobacterial processes are presented, including detailed recommendations for the prediction of growth (under phototrophic, heterotrophic, and mixotrophic conditions), nutrient uptake, carbon uptake and storage, and respiration. © 2018 The Authors
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Ouassim Bara, Hubert Bonnefond, Olivier Bernard.
PROCEEDINGS
Abstract
The idea relying on attached culture for microalgae production has attracted manyinterest these past years due to their energy efficiency and low water usage. Microalgae cangrow and attach to the surface of an appropriate material to form a biofilm. In this paper, arotating algal biofilm (RAB) model is introduced. It is based on the Han model. How lightaffects the growth and productivity of microalgae and thus the formed biofilm will be discussedthrough model development, more importantly, it will be seen that taking into considerationlight dilution factor can increase productivity. The benefit of the system is assessed when theconveyer velocity is fast enough. Simulation show an optimal folding of the conveyer. Actualproductivities for moderate velocities are assessed and compared to these extreme cases.
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Walid Djema, Laetitia Giraldi, Olivier Bernard.
DYCOPS 2019 - 12th IFAC Symposium on Dynamics and Control of Process Systems, including Biosystems (2019).
COMM
Abstract
We investigate a minimal-time control problem in a chemostat continuous photo-bioreactor model that describes the dynamics of two distinct microalgae populations. More precisely, our objective in this paper is to optimize the time of selection-or separation-between two species of microalgae. We focus in this work on Droop's model which takes into account an internal quota storage for each microalgae species. Using Pontryagin's principle, we develop a dilution-based control strategy that steers the model trajectories to a suitable target in minimal time. Our study reveals that singular arcs play a key role in the optimization problem. A numerical optimal-synthesis, based on direct optimal control tools, is performed throughout the paper, thereby confirming the optimality of the provided feedback-control law, which is of type bang-singular.
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Riccardo De-Luca, Fabrizio Bezzo, Quentin Béchet, Olivier Bernard.
Complexity (2019).
ART
Abstract
Outdoor biofuel production from microalgae is a complex dynamical process submitted to climatic variations. Controlling andoptimizing such a nonlinear process strongly influenced by weather conditions is therefore tricky, but it is crucial to make thisprocess economically sustainable. The strategy investigated in this study uses weather forecast coupled to a detailed predictivemodel of algal productivity for online optimization of the rates of fresh medium injection and culture removal into and from thepond. This optimization strategy was applied at various climatic conditions and significantly increased productivity compared to astandard operation with constant pond depth and dilution rate, by up to a factor of 2.2 in a Mediterranean climate in summer. Athorough analysis of the optimizer strategy revealed that the increase of productivity in summer was achieved by finding a trade-off between algal concentration to optimally distribute light and pond temperature to get closer to optimal growth temperature.This study also revealed that maintaining the temperature as high as possible is the best strategy to maximize productivity in coldclimatic conditions
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Cecile Lopez, Esteve Noguera, Vaia Stavropoulou, Elie Robert, Zakia Aid, Paola Ballerini, Chrystèle Bilhou-Nabera, Hélène Lapillonne, Fabien Boudia, Cécile Thirant, Alexandre Fagnan, Marie-Laure Arcangeli, Sarah Kinston, M'Boyba Diop, Bastien Job, Yann Lécluse, Erika Brunet, Loelia Babin, Jean Luc Villeval, Eric Delabesse, Antoine H.F.M. Peters, William Vainchenker, Muriel Gaudry, Riccardo Masetti, Franco Locatelli, Sebastien Malinge, Claus Nerlov, Nathalie Droin, Camille Lobry, Isabelle Godin, Olivier Bernard, Berthold Göttgens, Arnaud Petit, Françoise Pflumio, Juerg Schwaller, Thomas Mercher.
Cancer Discovery (2019).
ART
Abstract
Fusion oncogenes are prevalent in several pediatric cancers, yet little is known about the specific associations between age and phenotype. We observed that fusion oncogenes, such as ETO2-GLIS2, are associated with acute megakaryoblastic or other myeloid leukemia subtypes in an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed that ETO2-GLIS2 expression in fetal hematopoietic stem cells induced rapid megakaryoblastic leukemia whereas expression in adult bone marrow hematopoietic stem cells resulted in a shift toward myeloid transformation with a strikingly delayed in vivo leukemogenic potential. Chromatin accessibility and single-cell transcriptome analyses indicate ontogeny-dependent intrinsic and ETO2-GLIS2-induced differences in the activities of key transcription factors, including ERG, SPI1, GATA1, and CEBPA. Importantly, switching off the fusion oncogene restored terminal differentiation of the leukemic blasts. Together, these data show that aggressiveness and phenotypes in pediatric acute myeloid leukemia result from an ontogeny-related differential susceptibility to transformation by fusion oncogenes. SIGNIFICANCE: This work demonstrates that the clinical phenotype of pediatric acute myeloid leukemia is determined by ontogeny-dependent susceptibility for transformation by oncogenic fusion genes. The phenotype is maintained by potentially reversible alteration of key transcription factors, indicating that targeting of the fusions may overcome the differentiation blockage and revert the leukemic state.See related commentary by Cruz Hernandez and Vyas, p. 1653.This article is highlighted in the In This Issue feature, p. 1631.
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Olivier Bernard, Hubert Bonnefond, Antoine Sciandra, Eric Pruvost, Ghjuvan Micaelu Grimaud.
PATENT
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Marjorie Morales, Pierre Collet, Laurent Lardon, Arnaud Helias, Jean-Philippe Steyer, Olivier Bernard.
COUV
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Walid Djema, Laetitia Giraldi, Olivier Bernard.
UNDEFINED
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Marie-Ange Einaudi, Olivier Bernard, Sophie Tardieu.
Santé Publique (2019).
ART
Abstract
Some prenatal situations may be characterized as concerning on the medico-psycho-social level, leaving a risk of danger to the unborn child, raising different issues between prevention and protection, legal and justified. The objectives were to evaluate the professionals’ perceptions with respect to the most worrying prenatal situations, to assess the practices of care, and to identify potential measures for improvement.
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Francis Mairet, Olivier Bernard.
PLoS Computational Biology (2019).
ART
Abstract
Because of the inherent complexity of bioprocesses, mathematical models are more and 1 more used for process design, control and optimization etc... These models are generally 2 based on a set of biochemical reactions. Model equations are then derived from mass balance, 3 coupled to empirical kinetics. Biological models are nonlinear and represent processes, 4 which by essence are dynamic and adaptive. The temptation to embed most of the biology 5 is high, with the risk that calibration would not be significant anymore. The most important 6 task for a modeler is thus to ensure a balance between model complexity and ease of use. 7 Since a model should be tailored to the objectives which will depend on applications and 8 environment, a universal model representing any possible situation is probably not the best 9 option. 10 Here are twelve tips to develop your own bioprocess model. For more details on bioprocess 11 modelling, the readers could refer to [1]. More tips concerning computational aspects can 12 be found in [2, 3].
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Freddy Guihéneuf, Antoine Sciandra, Olivier Bernard, Hubert Bonnefond.
EPC7 - 7th European Phycological Congress (2019).
COMM
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Sarah Leclerc, Erik Smistad, Thomas Grenier, Carole Lartizien, Andreas Ostvik, Frédéric Cervenansky, Florian Espinosa, Torvald Espeland, Erik Andreas Rye Berg, Pierre-Marc Jodoin, Lasse Løvstakken, Olivier Bernard.
2019 IEEE International Ultrasonics Symposium (IUS) (2019).
COMM
Abstract
In this work, we present a novel attention mechanism to refine the segmentation of the endocardium and epicardium in 2D echocardiography. A combination of two U-Nets is used to derive a region of interest in the image before the segmentation. By relying on parameterised sigmoids to perform thresholding operations, the full pipeline is trainable end-to-end. The Refining U-Net (RU-Net) architecture is evaluated on the CAMUS dataset, comprising 2000 annotated images from the apical 2 and 4 chamber views of 500 patients. Although geometrical scores are only marginally improved, the reduction in outlier predictions (from 20% to 16%) supports the interest of such approach.
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Jacob J Lamb, Olivier Bernard, Shiplu Sarker, Kristian M Lien, Dag Roar Hjelme.
Renewable and Sustainable Energy Reviews (2019).
ART
Abstract
There is currently an increasing requirement for renewable fuel alternatives to replace fossil-based fuels as an energy source. Although biogas is not a new approach to producing renewable fuel, it could further be developed to improve its potential as an alternative energy source. To achieve this, vast improvements in the efficiency and cost of biogas production are essential. These enhancements require detailed systematic monitoring to attain a near-optimal biogas production process. To date, there is a striking imbalance between the inherent biological complexity of anaerobic digestion, and the minimal information currently measured on-line. Improvements in availability and cost of sensor technology used for determining the key compounds and their dynamics within the biogas processing plant will facilitate the further understanding of the biogas production process, preventing the biological process failure. The objective of this review is to assess colourimetric assays for variable detection in anaerobic digestion. Colourimetric assays (sensor assays based on coloured dyes) provide a stable, multivariate system for the detection of Volatile Fatty Acids (VFAs), but also provide a much deeper insight into the process by assessing other parameters, which, to date have never been
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Pierre-Olivier Lamare, Nina Aguillon, Jacques Sainte-Marie, Jérôme Grenier, Hubert Bonnefond, Olivier Bernard.
Automatica (2019).
ART
Abstract
Microalgae are microorganisms which have been only recently used for biotechnological applications, especially in the perspective of biofuel production. Here we focus on the shape optimization and optimal control of an innovative process where the microalgae are fixed on a support. They are thus successively exposed to light and dark conditions. The resulting growth can be represented by a dynamical system describing the denaturation of key proteins due to an excess of light. A Partial Differential Equations (PDE) model of the Rotating Algal Biofilm (RAB) is then proposed, representing local microalgal growth submitted to the time varying light. An adjoint-based gradient method is proposed to identify the optimal (constant) process folding and the (time varying) velocity of the biofilm. When applied to a realistic case, the optimization points out a particular configuration which significantly increases the productivity compared to a base case where the biofilm is fixed.
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Andrea Fanesi, Armelle Paule, Olivier Bernard, Romain Briandet, Filipa Lopes.
Microorganisms (2019).
ART
Abstract
Microalgae biofilms have been proposed as an alternative to suspended cultures in 10 commercial and biotechnological fields. However, little is known about their architecture which 11 may strongly impact biofilm behavior, bioprocess stability and productivity. In order to unravel the 12 architecture of microalgae biofilms, four species of commercial interest were cultivated in 13 microplates and characterized using a combination of confocal laser scanning microscopy and FTIR-14 spectroscopy. In all the species, the biofilm biovolume and thickness increased over time and 15 reached a plateau after 7 days, the final biomass reached was very different though. The roughness 16 decreased during maturation, reflecting cell division and voids filling. The extracellular polymeric 17 substances content of the matrix remained constant in some species and increased over time in some 18 others. Vertical profiles showed that young biofilms presented a maximum cell density at 20 µm 19 above the substratum co-localized with matrix components. In mature biofilms, the maximum 20 density of cells moved at a greater distance from the substratum (30-40 µm) whereas the maximum 21 coverage of matrix components remained in deeper layer. Carbohydrates and lipids were the main 22 macromolecules changing during biofilm maturation. Our results revealed that the architecture of 23 microalgae biofilms is species-specific. However, time is similarly affecting the structural and 24 biochemical parameters. 25
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Margaux Caia, Freddy Guihéneuf, Hubert Bonnefond, Antoine Sciandra, Olivier Bernard.
AlguaEurope Conference (2019).
COMM
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Carlos Martinez, Francis Mairet, Luis Plaza, Antoine Sciandra, Olivier Bernard.
PROCEEDINGS
Abstract
The main resources limiting microalgae growth are typically phosphorus, nitrogen, and light. Based on the theory of the light limited chemostat, the variable cell quota approach, and photoacclimation models, we build a mathematical model for describing microalgae growth under limitation by these resources. The model is calibrated with a data set from the literature. Then, by numerical simulations, we find that under constant operation of the culture and constant environmental conditions (illumination, temperature, pH, etc.), solutions of the model approach towards either a positive or an extinction steady state. Based on the positive steady state, and in the context of wastewater treatment, we evaluate the capacity of microalgae to remove contaminants. We showed that the impacts of depth, incident light intensity, and dilution rate (or hydraulic retention time) have a crucial role on the optimization of the nutrient removal efficiency. (C) 2019, IFAC (International Federation of Automatic Control)
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Jérôme Grenier, Filipa Lopes, Freddy Guihéneuf, Hubert Bonnefond, Antoine Sciandra, Olivier Bernard.
AlgaEurope Conference (2019).
COMM
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Fotini Kostopoulou, Clementine Gabillaud, Elise Chapiro, Béatrice Grange, Julie Tran, Simon Bouzy, Michael Degaud, Hussein Ghamlouch, Magali Le Garff-Tavernier, Karim Maloum, Sylvain Choquet, Veronique Leblond, Jean Gabarre, Anne Lavaud, Véronique Morel, Damien Roos-Weil, Madalina Uzunov, Romain Guiéze, Olivier Bernard, Santos A. Susin, Olivier Tournilhac, Florence Nguyen-Khac.
Cancer Medicine (2019).
ART
Abstract
The different types of drug resistance encountered in chronic lymphocytic leukemia (CLL) cannot be fully accounted for by the 17p deletion (and/or TP53 mutation), a complex karyotype (CK), immunoglobulin heavy-chain variable region genes (IGHV) status and gene mutations. Hence, we sought to assess the associations between recurrent genomic abnormalities in CLL and the disease's development and outcome. To this end, we analyzed 64 samples from patients with CLL and gain of the short arm of chromosome 2 (2p+), which is frequent in late-stage and relapsed/refractory CLL. We found that fludarabine/cyclophosphamide/rituximab (a common first-line treatment in CLL) is not effective in removing the 2p+ clone - even in samples lacking a CK, the 17p deletion or unmutated IGHV. Our results suggest strongly that patients with CLL should be screened for 2p+ (using karyotyping and fluorescence in situ hybridization) before a treatment option is chosen. Longer follow-up is now required to evaluate bendamustine-rituximab, ibrutinib, and idelalisib-rituximab treatments.
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Jacob J Lamb, Olivier Bernard, Shiplu Sarker, Kristian M Lien, Dag Roar Hjelme.
Engineering in Life Sciences (2019).
ART
Abstract
Biogas production is becoming significantly viable as an energy source for replacing fossil-based fuels. The further development of the biogas production process could lead to significant improvements in its potential. Wastewater treatment currently accounts for 3% of the electrical energy load in developed countries, while it could be developed to provide a source of nitrogen and phosphorus, in addition to energy. The improvement of anaerobic digestion (AD) detection technologies is the cornerstone to reach higher methane productivities and develop fully automatized processes to decrease operational costs. New sensors are requested to automatically obtain a better interpretation of the complex and dynamical internal reactor environment. This will require detailed systematic detection in order to realize a near-optimal production process. In this review, optical fiber-based sensors will be discussed to assess their potential for use in AD. There is currently a disparity between the complexity of AD, and online detection. By improving the durability, sensitivity, and cost of dissolved H-2 (as well as H2S, acetic acid, ammonia, and methane) sensor technology, further understanding of the AD process may allow the prevention of process failure. The emergence of surface plasmon resonance (SPR) sensing with optical fibers coupled with the H-2-sensitive metal palladium, allows detection of dissolved hydrogen in liquid. By implementing these SPR sensors into AD, improvements to the biogas production process, even at small scales, may be achieved by guiding the process in the optimum direction, avoiding the collapse of the biological process. This review intends to assess the feasibility of online, cost-effective, rapid, and efficient detection of dissolved H-2, as well as briefly assessing H2S, acetic acid, ammonia, and methane in AD by SPR.
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Pierre-Olivier Lamare, Nina Aguillon, Jacques Sainte-Marie, Jérôme Grenier, Hubert Bonnefond, Olivier Bernard.
REPORT
Abstract
Microalgae are microorganisms which have been only recently used for biotechnological applications, especially in the perspective of biofuel production. Here we focus on the shape optimization and optimal control of an innovative process where the microalgae are fixed on a support. They are thus successively exposed to light and dark conditions. The resulting growth can be represented by a dynamical system describing the denaturation of key proteins due to an excess of light. A Partial Differential Equations (PDE) model of the Rotating Algal Biofilm (RAB) is then proposed, representing local microalgal growth submitted to the time varying light. An adjoint-based gradient method is proposed to identify the optimal (constant) process folding and the (time varying) velocity of the biofilm. When applied to a realistic case, the optimization points out a particular configuration which significantly increases the productivity compared to a base case where the biofilm is fixed.
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Leslie Meier, Carlos Martínez, Carlos Vílchez, Olivier Bernard, David Jeison.
Energy (2019).
ART
Abstract
The use of microalgae cultures has been proposed as an innovative method to remove CO2 from biogas. However, the design of a large-scale installations requires the identification of key operational parameters and the determination of the maximum treatment capacity of the system. The aim of this work is to advance in that direction, using mathematical modelling. A model was developed, considering a system composed of a bubble column connected with an open photobioreactor. Simulations were carried out to evaluate the operation of a potential large-scale system. Results show that biogas upgrading would be feasible at large scales. At a biogas treatment capacity of 0.12 m(3) d(-1) per m(3) reactor, an upgraded biogas with less than 3 and 1% of CO2 and O-2, respectively, could be obtained. Under such condition, more that 80% of the inorganic carbon from the biogas would be transformed into biomass. Considering the low volumetric capacity of the system, its feasibility is expected to be determined by the biomass economic value.
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Florent Guérin, Lionel Charre, Stéphanie Jasienski, Mathieu Duché, Stéphanie Franchiabella, Olivier Bernard, Emmanuel Jacquemin, Hélène Agostini, Frédéric Gauthier, Sophie Branchereau.
Journal of Pediatric Surgery (2019).
ART
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Carlos Martínez, Francis Mairet, Pierre Martinon, Olivier Bernard.
IFAC-PapersOnLine (2019).
ART
Abstract
Microalgae cultivation with wastewater is a promising way of reducing the energetic needs for wastewater treatment and the costs of biofuel production. However, the very turbid medium is not favorable for the development of microalgae. Indeed, light, the key element for photosynthesis, rapidly vanishes along depth due to absorption and scattering. Therefore it is crucial to understand the effects of the depth on turbid cultures. In this work, we study theoretically the long-term behavior of a continuous culture of microalgae exposed to a periodic source of light. By allowing periodic variations of the depth and the hydraulic retention time, we show that the microalgae population is forced to a periodic regime. Finally, we address numerically the problem of determining the optimal variations of the depth and the hydraulic retention time for maximizing the productivity of the culture in the periodic regime.
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David Demory, Anne-Claire Baudoux, Adam Monier, Nathalie Simon, Christophe Six, Pei Ge, Fabienne Rigaut-Jalabert, Dominique Marie, Antoine Sciandra, Olivier Bernard, Sophie Rabouille.
The International Society of Microbiologial Ecology Journal (2019).
ART
Abstract
Photosynthetic picoeukaryotes in the genus Micromonas show among the widest latitudinal distributions on Earth, experiencing large thermal gradients from poles to tropics. Micromonas comprises at least four different species often found in sympatry. While such ubiquity might suggest a wide thermal niche, the temperature response of the different strains is still unexplored, leaving many questions as for their ecological success over such diverse ecosystems. Using combined experiments and theory, we characterize the thermal response of eleven Micromonas strains belonging to four 1 species. We demonstrate that the variety of specific responses to temperature in the Micromonas genus makes this environmental factor an ideal marker to describe its global distribution and diversity. We then propose a diversity model for the genus Micromonas, which proves to be representative of the whole phytoplankton diversity. This prominent primary producer is therefore a sentinel organism of phytoplankton diversity at the global scale. We use the diversity within Micromonas to anticipate the potential impact of global warming on oceanic phytoplankton. We develop a dynamic, adaptive model and ran forecast simulations, exploring a range of adaptation time scales, to probe the likely responses to climate change. Results stress how biodiversity erosion depends on the ability of organisms to adapt rapidly to temperature increase.
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Hussein Kanso, Bénédicte Quilot-Turion, Mohamed-Mahmoud Memah, Olivier Bernard, Jean-Luc Gouzé, Valentina Baldazzi.
FOSBE 2019 - 8th Conference on Foundations of Systems Biology in Engineering (2019).
COMM