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International audience; Hydrogen is more and more considered for the decarbonization of energy uses, especially for transport applications. To reach a power range of several hundred kilowatts usually met in high power applications, an association of fuel cells in multi-stack is necessary. An adapted control must therefore be designed to share the requested power among the fuel cells. This paper presents an optimized power allocation strategy based on the minimization of the consumption of the stacks. The polarization curves are considered to take the fuel cell characteristics and its state of health into account. The proposed control strategy is experimentally validated thanks to a computation in real-time on a test bench, emulating four stacks of fuel cells with different states of health. The results show the effectiveness of the developed strategy, allowing the consumption to be reduced by 1.2 % compared to a strategy based on a fair distribution. Moreover, the reconfigurability of the power allocation is validated by considering the unavailability of some of the stacks.

International audience; This paper presents a semi-empirical model of Proton Exchange Membrane Fuel Cell (PEMFC), combining electrical and thermal phenomena and system degradations. The originality of our approach is the link between activation and diffusion phenomena by using a semi-empirical equation to create a new fast and accurate PEMFC model. Then, a degradation model is defined and adapted to energy management needs. The aim of this design is to study fault tolerant multi stack Fuel Cell (FC) systems, to study their interactions with converters and to design optimal control and adaptative management rules. The degradation model is used to adapt management laws according to the state of health of each stack. This work also offers an exhaustive analysis of the existing models available in the literature including a set of models compatible with the needs of Modular Fuel Cells (MFC) studies.

To ensure the economic viability and the reliability of microgrid operation, an adapted energy management system (EMS) has to be designed. Most of the studies have discussed optimization-based approaches, for example with a mixed-integer linear programming (MILP) problem, to get the best operating profiles for each microgrid device allowing economic, technical or environmental objectives to be met. However, this kind of EMS requires a forecasting ability of the power generation and of the demand, and the management of the uncertainties. In some microgrids, especially in industrial areas, the power generation and the load demand cannot be accurately forecasted. In such cases, only a rule-based algorithm can be considered for the real-time energy management. In this paper, a rule-based algorithm is proposed for the management of a seaport multi-energy microgrid, using electricity and hydrogen as energy vectors. The rules are designed on the basis of the results obtained with MILP problem solving with the aim being to maximize income and use the energy generated by the local energy sources as well as possible by taking dynamic pricing into account. Moreover, specific strategies are designed for the management of the electrolyzer and hydrogen tank to avoid premature ageing. The results show that the proposed real-time algorithm and rules enable the economic and energetic criteria to reach values close to those obtained with MILP problem solving, with an increase of the payback period less than 2%.

International audience; That work investigates the compatibility of voltage balancing algorithm and multilevel modulations of a three phase modular multilevel converter (MMC). A study of the "Reduced switching frequency" (RSF) voltage balancing algorithm with low frequency modulations is proposed. It is first shown that Nearest Level Modulation cannot be used in MMC with RSF algorithm. Two new hybrid modulations are then introduced, the Long Conduction time Pulse Width Modulation (LCPWM) and the Enhanced Long Conduction time Pulse Width Modulation (ELCPWM). They offer advantageous trade-off between switching frequency and voltage balancing accuracy with RSF algorithm. Based on innovative static carriers, they do not generate random narrow pulses, decreasing electrical stress on power transistors. The conduction times of the proposed modulations are deterministic and maximized. Their generation is highly simplified compared to triangular or saw-tooth carrier based modulations. An accurate simulation tool allows to compare various characteristics of proposed modulations to classical low frequency modulation and pulse width modulation on multi-megawatts three phase MMC.

The current evolution of technical and environmental regulations and the recent development of hydrogen mobility require technological breakthroughs in the industrial areas, such as in harbours. Thus, multi-energy microgrids integrating low-carbon energy sources, electrical and hydrogen loads and storage solutions have to be designed. To improve their economic viability, the microgrid components must be carefully sized and the energy must be distributed in the most cost-effective way at any time. So as to foster the expansion of multi-energy microgrids in industrial areas, we propose in this paper a two-level optimization for the energy management and the sizing, applied to an original multi-energy scenario considering electricity and hydrogen as energy vectors. The designed energy management optimization takes into account an objective of economic profitability and constraints related to the availability of the sources and storage solutions, their reliability and the costs. The sizing optimization aims to propose different solutions allowing the benefits to be maximized and the expenses to be minimized. One of the main contributions of the paper is to compare the possible ways of valorisation of the energy available in an industrial microgrid. The results show that the sale of hydrogen allows income to be increased, in addition to self-consumption and sale to the electrical grid, but the electrolyzer involves high investments costs. Finally, a sensitivity analysis is presented and shows that the investment costs of electrolyzer and battery and the hydrogen selling price are key points in the optimal design.

Recent Modular Multilevel Converter (MMC) topology allows for drastic improvements in power electronic conversion such as higher energy quality, lower power semiconductors electrical stress, decreased Electro-Magnetic Interferences (EMI), and reduced switching losses. MMC is widely used in High Voltage Direct-Current (HVDC) transmissions as it offers, theoretically, no voltage limit. However, its control electronic structure is not modular itself. Especially, the insulation voltage between the submodule gate drivers’ primaries and secondaries depends on the number of submodules. The converter voltage levels cannot be increased without designing all gate driver isolations again. To solve that issue, the novel concept of distributed galvanic insulation is introduced for multilevel converters. The submodule’s gate drivers are daisy-chained, which naturally reduces the insulation voltage to the submodule capacitor voltage, regardless of the number of submodules. The MMC becomes truly modular as the number of submodules can be increased without impacting on the previous control electronic circuit. Such an innovative control structure weakens the link between the main control unit and the gate drivers. This inherent structural problem can be solved through the use of Smart-Gate Drivers (SGD), as they are often equipped with fast and bidirectional communication channels, while highly increasing the converter reliability. The innovation proposed in that work is the involvement of smart gate drivers in the distributed galvanic insulation-based MMC control and monitoring. First, the numerous benefits of smart gate drivers are discussed. Then, an innovative Voltage Balancing Algorithm directly integrated on the chained gate drivers is proposed and detailed. It features a tunable parameter, offering a trade-off between accurate voltage balancing and execution time. The proposed embedded algorithm features a low execution time due to simultaneous voltage comparisons. Such an algorithm is executed by the gate drivers themselves, relieving the main control unit in an original decentralized control scheme. A simulation model of a multi-megawatts three-phase grid-tied MMC inverter is realized, allowing validation of the proposed algorithm. Matlab/Simulink logic blocs allow us to simulate a typical CPLD/FPGA component, often embedded on smart gate drivers. The converter with the proposed embedded algorithm is simulated in steady-state and during load impact. The controlled delay and slew rate inferred by the algorithm do not disturb the converter behavior, allowing its conceptual validation.

This paper presents an energy management algorithm based on a new adaptive filtering method for a multi-sources battery-ultracapacitor electric vehicle. Compared to literature where most of the filtering techniques are developed based on empirical knowledge of the system, the proposed adaptation method is performed online to optimize a cost function that considers the state of charge of the ultracapacitor. The developed approach allows a better power sharing between both electric sources while respecting their constraints and physical limitations. Simulations on Matlab/Simulink validate the performances of the proposed method.

This paper proposes a photovoltaic-battery storage system (PV-BSS) to improve the reliability of a power distribution network with frequent outages, encountered in many developing countries. The system sizing methodology takes into account the loss of power supply probability (LPSP) and the cost of energy. A genetic algorithm is used for achieving improved reliability with an optimal cost of energy by determining the Pareto solutions set. A detailed outage survey characterized by the number and duration of outages experienced by a typical customer on a selected weak distribution system is examined. For this study, real load demand and outage data have been recorded for a university building in Ethiopia. Moreover, long-term outage data was analyzed and studied to understand the overall outage situation, which clearly showed its randomness. The proposed PV-BSS helps to reduce the loss of power and achieve a reliable power supply with zero LPSP for the case considered. Currently, without any standby and backup system, the building has a poor power supply with an erratic outage of about 6% LPSP.

This paper presents a new energy management algorithm based on filtering for battery-ultracapacitor electric vehicles. Compared to the passive filtering techniques, the developed strategy allows a best control of the ultracapacitor state of charge and achieves an optimization of the system electric losses. This is achieved by an online optimization of a cost function. Simulations validate the performances of the proposed method.

To assess the difference in the fate of the antibiotic colistin (COLI) after its pulmonary delivery as a powder or a solution, we developed a COLI powder and evaluated the COLI pharmacokinetic properties in rats after pulmonary administration of the powder or the solution. The amorphous COLI powder prepared by spray drying was characterized by a mass median aerodynamic diameter and fine particle fraction of 2.68 &plusmn, 0.07 &micro, m and 59.5 &plusmn, 5.4%, respectively, when emitted from a Handihaler&reg, After intratracheal administration, the average pulmonary epithelial lining fluid (ELF): plasma area under the concentration versus time curves (AUC) ratios were 570 and 95 for the COLI solution and powder, respectively. However, the same COLI plasma concentration profiles were obtained with the two formulations. According to our pharmacokinetic model, this difference in ELF COLI concentration could be due to faster systemic absorption of COLI after the powder inhalation than for the solution. In addition, the COLI apparent permeability (Papp) across a Calu-3 epithelium model increased 10-fold when its concentration changed from 100 to 4000 mg/L. Based on this last result, we propose that the difference observed in vivo between the COLI solution and powder could be due to a high local ELF COLI concentration being obtained at the site where the dry particles impact the lung. This high local COLI concentration can lead to a local increase in COLI Papp, which is associated with a high concentration gradient and could produce a high local transfer of COLI across the epithelium and a consequent increase in the overall absorption rate of COLI.

This paper presents the optimization of the driving strategy of a high efficiency fuel cell based power train. This power train is developed to equip a light duty urban-concept vehicle that runs energetic races. The objective is to go the furthest with the lowest quantity of fuel. A comprehensive dynamical model is presented, including the mechanical requirement, the thermal behavior of the fuel cell stack and the various losses and consumptions of the power train devices. This model is next integrated into a global optimization algorithm, to determine the best race strategy to be adopted. These results are validated on experimental measurements, obtained during a real race at the Shell Eco-Marathon, in 2015.

In this work, we report the existence of a stoichiometric regime where the performances of operating polymer electrolyte membrane (PEM) fuel cells are entirely governed by the mass transport in the cathode channels. An analytical model of the fuel cell stoichiometric regime is derived and evidenced experimentally: from the cell spectral signature at low frequency based on electrochemical impedance spectroscopy, and from the current density distribution measured using a segmented current collector. The existence of such regime provides a simple way to characterize, model and predict PEM fuel cell performances.

This paper presents a new Energy Management Strategy (EMS) based on frequency separation and fuzzy logic control for a multi-sources system. The studied system is an electric vehicle with hybrid sources including a fuel cell (FC), a battery and an ultracapacitor. Each source is controlled using a DC/DC converter connected to the DC-bus. To maintain a constant DC-bus voltage, a Lyapunov based controller is developed. The overall energy flow of the system is managed using a filtering-based EMS which allows a flexible use of energy sources by self-adapting to the system state evolution. The proposed approach protects the fuel cell and the battery from strong power dynamics, and coordinates the distribution of the energy demand between the battery and the ultracapacitor according to their state of charge. Simulations on MATLAB/SIMULINK, using a real current profile in an urban driving situation, validate the performances of the proposed method.

International audience; The purpose of this study was to design inhalable sustained-release nanoparticle-in-microparticles, i.e. nano-embedded microparticles, for the lung delivery of chloramphenicol or thiamphenicol as aerosols. The palmitate ester prodrugs of the two antibiotics were used to prepare PLGA-based nanoparticles or to form pure prodrug nanoparticles. Prodrug-loaded PLGA nanoparticles or pure prodrug nanoparticles were prepared using the emulsion-solvent evaporation method. Dry microparticle powders for inhalation were then produced by spray-drying the nanoparticle suspensions supplemented with lactose as a bulking agent and L-leucine as a dispersing enhancer. Examined under the scanning electron microscopy, the obtained microparticles appeared to be spherical and shriveled, with no crystal-like structures. Drug loading was satisfactory (14 to 34% (m/m)) and the aerodynamic properties determined with a Next Generation Impactor were appropriate for lung delivery, with mass median aerodynamic diameters close to 3 μm. The in vitro release profiles showed that sustained released was achieved with these formulations, with an almost complete release over 14 days.

This paper addresses the simulation of complex systems which consider phenomena with different time scales. Such problems are encountered on studies of electrical systems which try to take into account the simulation of the power converter and its control laws, over representative operating cycles of several hours. Moreover, when storage elements are integrated into a power chain, their aging may need the designer to consider larger time scales, which can then exceed a few years. It is the reason why most studies separate the time scales between the slow dynamics for the energetic, thermal and aging phenomena, and the fast ones to study the power converter and its control laws. This paper presents an original cycle-based and multi-rate method for the simulation of power systems with a wide range of time scales and with high mutual dependency between the fast and slow state variables. This method is applied to the supercapacitor energy storage system of a full-electric ferry. The proposed simulation results take into account at the same time the switching of the power converter and the aging of the supercapacitor, with a reduction of the computational effort greater than 1 0 5 . In other words, while a full calculation of the problem takes 10 centuries on a personal computer, the proposed method permits to have the same result in only 15 days.

Proton exchange membrane fuel cell is a well-known technology that has shown high efficiency and performance as a power system compared to conventional sources such as internal combustion engines. Especially, open cathode proton exchange membrane is growing more popular thanks to its simple structure, low cost and low parasitic losses. However, the open cathode fuel cell performance is highly related to the operating temperature variation and the airflow rate which is adjusted through the fan voltage. In this regard, the present study investigates the thermal management of an open cathode proton exchange membrane fuel cell. The objectives are the stack performance improvement and the stack degradation prevention. Indeed, a safety and optimal operating zone governed by the load current, the stack temperature and the air stoichiometry, is designed. This optimal operating zone is defined based on the system thermal balance and the operating constraints. Hence, the proposed control strategy deals concurrently with the stack temperature regulation and the air stoichiometry adjustment to guarantee the goals achievement. The performance of the proposed control strategy is verified through experimental studies with different operating conditions and results prove its efficiency. To properly design an appropriate control strategy, a multiphysic fuel cell model is developed based on acausal approach by mean of Matlab/Simscape and experimentally validated.

Intermittent power interruptions and blackouts with long outage durations are very common, especially on weak distribution grids such as in developing countries. This paper proposes a hybrid photovoltaic (PV)-battery-system sizing optimization through a genetic algorithm to address the reliability in fragile grids measured by the loss of power supply probability (LPSP) index. Recorded historical outage data from a real stochastic grid in Ethiopia and measured customer load is used. The resulting hybrid-system Pareto solutions give the flexibility for customers/power utilities to choose appropriate sizes based on the required reliability level. To evaluate the sizing solutions’ robustness, this work considers and compares grid outage modeling through two different approaches. The first is a Markov model, developed to be minimally implemented with limited outage data available. The second is a Weibull model, commonly used to describe extreme phenomena and failure analysis. It is more faithful in reproducing the dispersion of outage events. Using these models, the effectiveness and performance of the PV-battery system is verified on a large number of simulated outage scenarios, to estimate the real performance of the optimized design. It leads to a more accurate evaluation of the behavior of a renewable power system to a weak and unreliable electrical grid.

International audience; Pulmonary delivery of fluoroquinolones (FQs) is an interesting approach to treat lung infections as it may lead to high local concentrations while minimizing systemic exposure. However, FQs have a rapid diffusion through the lung epithelium giving the pulmonary route no advantage compared to the oral route. Interactions between FQs and metal cations form complexes which limit the diffusion through the epithelial barrier and would reduce the absorption of FQs and maintain high concentrations in the lung. The effects of this complexation depend on the FQ and the metal cations and optimum partners should be selected through in vitro experiments prior to aerosol drug formulation. In this study, CIP was chosen as a representative FQ and 5 cations (Ca2+, Mg2+, Zn2+, Al3+, Cu2+) were selected to study the complexation and its effects on permeability, antimicrobial efficacy and cell toxicity. The results showed that the apparent association constants between CIP and cations ranked with the descending order: Cu2+>Al3+>Zn2+>Mg2+>Ca2+. When a target of 80% complexation was reached with the adequate concentrations of cations, the CIP permeability through the Calu-3 lung epithelial cells was decreased of 50%. Toxicity of the CIP on the Calu-3 cells, with an EC50 evaluated at 7μM, was not significantly affected by the presence of the cations. The minimum inhibitory concentration of CIP for Pseudomonas aeruginosa was not affected or slightly increased in the range of cation concentrations tested, except for Mg2+. In conclusion, permeability was the main parameter that was affected by the metal cation complexation while cell toxicity and antimicrobial activity were not or slightly modified. Cu2+, with the highest apparent constant of association and with no effect on cell toxicity and antimicrobial activity of the CIP, appeared as a promising cation for the development of a controlled-permeability formulation of CIP for lung treatment.

This paper presents a general multi-rate method for the simulation of power systems with a wide range of time scales and with high mutual dependency between the fast and slow state variables. The original concept developed in this work relies on a cycle-based problem formulation, which consists in finding the repeating operation sequences of the system, at the different time scales. Next, a discrete form version of a conventional second order variable step solver is proposed and allows the extrapolation of the results beyond a large number of cycles, while maintaining and controlling a predetermined error tolerance on the state variables. This cycle-based formulation is applied to the ageing behaviour simulation of the energy storage unit of an all-electric ferry which only uses supercapacitors as energy storage. This problem needs the simulation of the electrical power operation of the boat, throughout its lifetime of 20 years. With this original cycle-based formulation, the computation effort can be reduced by several hundreds while maintaining low error tolerances.

International audience; This paper presents an energy management algorithm to be embedded for a residential application disconnected from the power grid. The multisource system studied includes solar panels as a renewable energy source, a fuel cell as a secondary source, three batteries and a bank of supercapacitors as storage systems. The proposed algorithm uses as input data, future estimates obtained from power consumption and meteorological forecasting data, and historical of the load power and the renewable power obtained from measurements. It is assumed that these two input powers are imposed and uncontrollable. In the case where the future estimates have errors compared to what has actually been measured, a mathematical approach shows that the algorithm is able to compensate these forecasting errors by sharing them between the different sources of the system while respecting their different characteristics. In addition to the optimal energy distribution, the algorithm gives the optimal size of each source and storage devices. In this work, the total cost of the system is chosen as the criteria to be optimized. The simulations are carried out over a year, with a time step of 1 second and in the presence of significant forecasting errors. The results obtained are particularly convincing and make it possible to validate this energy management strategy.

Aerosol antibiotics are an interesting alternative to oral or intravenous therapy in Cystic Fibrosis lung infections. Levofloxacin (LVX) inhaled solution is already an effective option. In this study, the aim was the development of LVX-loaded PLGA microspheres (MS) for pulmonary administration as a dry powder. MS were prepared, for the first time, by a modified double emulsion solvent evaporation method with premix membrane homogenization. Aqueous phases were saturated with LVX and a fatty acid (lauric acid) was added to avoid the drug escaping from the organic phase. MS were characterized in terms of size, drug content, morphology and in vitro release properties. X-ray diffraction, Fourier-transform infrared spectroscopy, differential and gravimetric thermal analysis, and cytotoxicity analyses were performed. Results showed this new method increased the drug loading while maintaining an adequate (∼5 µm) particle size and controlled release. Compared to a solution for inhalation, these properties combined with the dry-powder nature of these MS will improve patient compliance. The incorporation of lauric acid was not advantageous because the particle size was higher and no improvements concerning the sustained release occurred. LVX was molecularly dispersed in the matrix, or it was in amorphous state, as confirmed by the physico-chemical analyses. Calu-3 cell viability assays demonstrated no cytotoxicity for these MS, making them a promising system for LVX pulmonary delivery.

This paper presents an improved control strategy of an open cathode proton exchange membrane fuel cell, which ensures an efficient operation and a long lifetime of the stack. The key idea is to control simultaneously and with only one actuator, the air supplying and the stack temperature, in order to avoid, in the one hand oxygen starvation or the drop of system efficiency, and in the other hand to reduce the layers lifespan. For analyzing the proposed control a fuel cell multi-physic model is developed. This model is implemented in Matlab/Simscape and experimentally validated in a steady-state mode. Through this proposed model, which combine electrical and thermal model of proton exchange membrane, it is possible to follow the temperature change within fuel cell. The control performance is discussed and evaluated by simulations.

This paper presents a new algorithm of electric energy management of hybrid power systems for self-consumption in isolated areas. This algorithm is inspired by the frequency separation method. Indeed, it is based on the calculation of sliding averages using centered moving average filters, which allow simultaneous and natural processing of measurement data (past) and load and sunshine forecast (future). Moreover, this algorithm has no limits of degrees of freedom and can handle more than two sources of energy without resorting to complex problems. The algorithm is tested on a hybrid system composed of solar panels as a renewable energy source, a fuel cell as a secondary source, a battery bank and a supercapacitor bank as energy storage systems. The main aim of the proposed strategy is to minimize the total operating cost of the system while satisfying the constraints required by the energy storage systems. Furthermore, the robustness of the proposed method is highly improved through the addition of an automatic correction process. The simulation results are convincing and validate the proposed energy management strategy.

International audience; This article elaborates a techno-economic approach that aims to optimize the conversion and energy storage unit chain of the first quick charge plug-in ferry. The choice of supercapacitors is motivated and then compared to other energy storage units for different kind of ferry exploitation. Several models were developed to be coupled with a global techno-economic model considering an exploitation strategy. In the last part, a typical application illustrates the cost reduction compared to the standard sizing approach.

In this paper, safe techno-economic sizing methodology of a standalone photovoltaic system is investigated. It is proposed to size the system on the basis of solar radiation measurements. Then, Markov transition matrices (MTM) are used to simulate stochastic cloud cover sequences. Each sizing is then tested on a large number of scenarios. It is thus possible to use a statistical approach of the sizing results, in particular on the Loss of Power Supply Probability (LPSP), which is highly sensitive to the stochastic nature of cloud cover. A case study (Saint-Martin en Haut, in France) is given to illustrate this methodology.

Polymer Electrolyte Membrane (PEM) fuel cells are considered as promising clean sources for automotive applications. A key challenge to reduce the cost of this technology is to increase the power density by operating PEM fuel cells at high current densities. Part of the research are focused in developing and designing new materials for this technology such as advanced catalyst layers (CL), new gas diffusion layers (GDL) structure, or innovative cell assembly conditions (clamping pressure, channel design…)[1]. To assess the performance of new materials, in situ characterisation techniques are required. Electrochemical impedance spectroscopy (EIS) is one of the most used technique to characterise the material impact onto the fuel cell mass/charge transfer, ohmic resistance and mass transport. However, due to the large number of parameters which has to be identified, inaccuracy in the identification process may arise leading to incorrect fuel cell material properties characterisation [2]. In authors’ recent work [3], it was shown that current density distributions can be used as a useful information to characterise fuel cell material properties. Thus, in this communication we will present a segmented cell designed and built to measure current density distribution along the channel while allowing optical access inside the channel to visualise the presence of liquid water. A range of fuel cell GDLs is characterised in situ in this cell for a range of operating conditions. The effective diffusivity of the GDLs is directly obtained from the current density distribution without any knowledge of the other fuel cell parameter (membrane ohmic resistance or CL kinetics). The values of effective diffusivity obtained using our methodology are compared to the ones obtained through EIS measurements, and their respective accuracy will be discussed. In addition, examples on the use of this characterisation cell to assess the performance of channel designs and fuel cell assembly conditions will be given. The results presented in this communication will introduce a novel fuel cell characterisation methodology which can strongly improve the development of more efficient fuel cell systems. References [1] T. Yoshida, K. Kojima, Toyota MIRAI Fuel Cell Vehicle and Progress Toward a Future Hydrogen Society, Interface Mag. 24 (2015) 45–49. [2] S. Chevalier, D. Trichet, B. Auvity, J.C. Olivier, C. Josset, M. Machmoum, Multiphysics DC and AC models of a PEMFC for the detection of degraded cell parameters, Int. J. Hydrogen Energy. 38 (2013) 11609–11618. [3] S. Chevalier, C. Josset, B. Auvity, Analytical solutions and dimensional analysis of pseudo 2D current density distribution model in PEM fuel cells, Renew. Energy. 125 (2018) 738–746.

This paper proposes a simple and effective method to reduce speed ripples of permanent magnet synchronous machines (PMSMs) under low-speed working conditions. The treated issue is related to the periodic torque ripples, which induce speed oscillations that deteriorate the drive performance. The main idea of the proposed method is to modify a conventional PMSM controller by superposing an appropriate compensation signal to the quadratic-current reference. The proposed approach allows the reduction of speed ripples at low speed through a simple compensation signal and does not require a hard calculation cost. A theoretical analysis is presented, and both simulation and experimental results are presented to validate the proposed compensation method.

Pulmonary administration enables high local concentrations along with limited systemic side effects but not all antibiotics could be good candidates. In this perspective, diffusion of the antibiotic chloramphenicol (CHL) and thiamphenicol (THA) through the lung has been evaluated to reassess their potential for pulmonary administration. The apparent permeability (Papp) was evaluated with the Calu-3 cell model. The influence of drug transporters was assessed with the PSC-833, MK-571, and KO-143 inhibitors. The influence of CHL and THA on the cell uptake of rhodamin 123 and fluorescein was also evaluated. Absorptive Papp of CHL and THA was concentration independent with CHL Papp 4 times higher than that of THA. Secretory Papp of CHL was concentration independent, whereas it was concentration dependent for THA with an efflux ratio of 3.6 for the lowest concentration. The use of inhibitors suggested that CHL and THA were substrates of efflux transporters but with a low affinity. In conclusion, the permeability results suggest that the pulmonary route may offer a biopharmaceutical advantage only for THA. Owing to the influence of drug transporters, a higher concentration in the lung than in the plasma is expected mostly for THA, whatever the route of administration.

This paper presents a pseudo 2D multiphysics A.C. and D.C. model that has been successfully used with Electrochemical impedance spectroscopy (EIS) measurements to detect cells state-of-health in a PEMFC stack. The model is able to reproduce the gas concentration oscillations that develop along the cell channel while doing EIS measurements. This feature makes it possible to explicitly take into account the air stoichiometry effects on cells state-of health. The model being both static and harmonic, the identification of model parameters is based on static cell data (current and voltage) and on measured cells impedance spectra. The cells state-of-health is presented in terms of repartition of losses due to four limiting phenomena: the membrane ionic resistance, the mass and charge transport limitations in the electrode, the mass transport limitations through GDLs and along the cell channels and the kinetic irreversibilities. When coupled with pressure drop measurements across the stack, it has been possible to prove that flooding conditions for the stack leads to inhomogeneous cells state-of-health: on one hand, most of the cells get flooded while, on the other hand, some of them remain in the nominal conditions.

This work aimed at designing a formulation based on nanostructured lipid carriers (NLC) for transdermal co-administration of olanzapine and simvastatin, using passive and active strategies in a combined in vitro/in vivo development approach. NLC were prepared by two distinct methods, namely solvent emulsification-evaporation (SE/E) and high pressure homogenization (HPH). HPH was selected on the basis of a better performance in terms of drug loading and in vitro permeation rate. Several mathematical models were used to elucidate the release mechanisms from lipid nanoparticles. In vitro release kinetics was shown to be driven by diffusion, but other mechanisms were also present, and supported the feasibility of using NLC for sustained drug delivery. The in vitro skin studies showed that the chemical penetration enhancers, limonene and ethanol, added to the NLC formulations, promoted a synergistic permeation enhancement of both drugs, with olanzapine exhibiting a higher permeation than simvastatin. Transdermal administration to rats resulted in steady-state levels reached at around 10h and maintained for 48h, again with olanzapine exhibiting a better permeation rate. The pharmacokinetic parameters indicated that the NLC dispersion displayed a better in vivo performance than the gel, which was consistent with the in vitro results. These differences were, however, negligible in the flux values, supporting the use of gel as a final, more convenient, formulation. The in vivo experiments in rats correlated well with in vitro findings and revealed that the combined use of ethanol and limonene, incorporated in the NLC formulation, provided the main driving force for drug permeation. The Dermaroller® pretreatment did not significantly enhance drug permeation, supporting the use of passive methods as suitable for a transdermal delivery system. Furthermore, this work may provide a promising proof-of-concept for further clinical application in the treatment of schizophrenia and associated disorders, combined with dyslipidemia.

The present paper proposes a new 2D modelling of ac impedance spectra of polymer electrolyte fuel cells (PEMFC). The computational domain includes the Membrane Electrode Assembly, the Gas Diffusion Layers and the channels on both the anode and cathode sides. The model takes into account the main fuel cell phenomena, i.e. reactants, charges transport and transfer and electrochemical reactions. First, the partial differential equations are solved in the steady state regime, then in the frequency domain in order to obtain the cell dynamic behaviour at different potentials. Experimental PEMFC impedance spectra are satisfactory reproduced over a relative large potentials range using only one set of model parameters. Numerical analysis of the key model parameters linked to the cell flooding state has been done. It is concluded that at least two impedance spectra at low and high potential are needed in order to discriminate the nature and the location of the cell degradations (anode or cathode, electrode or GDL). Based on a least square criterion, the model inversion is presented and several cell flooding scenarios have been precisely identified.

A rifampicin-hydroxypropyl-beta-cyclodextrin (RIF-HPCD) complex solution and two RIF-loaded PLGA microspheres with slow or fast release rates were nebulized into the rat lungs for a comparative biopharmaceutical evaluation. A pharmacokinetic model was applied to model systemic RIF concentrations and to predict the RIF concentrations in the lung epithelial lining fluid (ELF). With intravenous RIF and nebulized RIF-HPCD, plasma profiles and predicted RIF ELF profiles were superimposed indicating that RIF diffused almost instantaneously through the broncho-alveolar barrier. 5h post administration RIF ELF predicted concentrations were in agreement with experimental concentrations determined using the broncho-alveolar lavage (BAL) sampling method. Microsphere formulations resulted in different plasma concentration profiles, demonstrating RIF sustained release. The PK model predicted the ELF concentrations to be much higher with microspheres than with nebulized and IV RIF, over a prolonged time period, which was confirmed by BAL sampling. In conclusion this work demonstrated the benefit of using sustained-release microspheres administered as aerosols to maintain, over a prolonged time period, high levels of pulmonary concentrations of drugs characterized by a rapid absorption through the broncho-alveolar barrier. Moreover, PK modeling was a useful tool to build concentration-versus-time profiles in non-readily accessible ELF compartment and to assess the biopharmaceutical properties of aerosol formulations for lung delivery.

A comparative pharmacokinetic study was conducted in rats after intratracheal aerosolization of levofloxacin, as a solution, as immediate-release chitosan microspheres or as sustained-release PLGA microspheres. A pharmacokinetic model was constructed to model levofloxacin concentrations both in plasma and in the lung epithelial lining fluid (ELF). The plasma and ELF experimental concentration profiles versus time were similar for the intravenous and intratracheal levofloxacin solutions and for the intratracheal levofloxacin-loaded chitosan microsphere dry powder, indicating that levofloxacin diffused almost instantaneously through the broncho-alveolar barrier and that the chitosan microspheres released levofloxacin very rapidly, as anticipated from in vitro release studies. The bioavailability for the intratracheal levofloxacin solution and intratracheal chitosan microspheres was estimated to be 98% and 71%, respectively, both with a direct release into the ELF compartment. The ELF-to-unbound plasma AUC ratios were slightly above 2 and may result from an efflux transport. For the intratracheal PLGA microspheres, a high ELF-to-unbound plasma AUC concentration ratio (311) was observed and high levofloxacin concentrations were maintained in ELF for at least 72h in consistency with the in vitro release studies. The bioavailability was 92%, with 19% of the dose released immediately (burst release) into the ELF and 73% released slowly into the ELF from a depot compartment, i.e. the PLGA microspheres, according to a Weibull model. These results highlight the benefit of using sustained-release microspheres administered as aerosols to provide and to maintain high pulmonary concentrations of an antibiotic characterized with a high permeability profile through the broncho-alveolar barrier. The sustained-release microsphere dry powder aerosol may therefore provide advantages over solutions or pure drug dry powders for inhalation in terms of treatment efficiency, ease of use and frequency of administration.

The objective of this paper is to present a new criterion for robust sizing of (Photovoltaic (PV) — Fuel cell (FC) — Batteries (Bat)) installation, with respect to the variability of the resource. After a presentation and modeling of the studied system, a multi-objective sizing using a genetic algorithm NSGA-II have been introduced. The study takes into account the aging of batteries and fuel cell for a total lifetime of 25 years for all the system. The sizing is based on an energy management by simulation of the system operation using 5 years of measurements from 2009 to 2013. A new criterion has been introduced for the choice of the reference solar radiation profile which considered here as the energy ressource of the system. This profile has been selected based on the analysis of the system sizing's robustness.

The solvent evaporation method with premix membrane homogenization was applied, with class-3 ethyl acetate as organic solvent, to produce narrowly size-distributed rifampicin (RIF)-loaded poly(lactide-co-glycolide) (PLGA) microspheres for sustained lung delivery as aerosol. Microsphere formulations (simple or multiple emulsions, different PLGA and RIF concentrations) and process parameters (transmembrane pressure, SPG membrane pore diameter) were investigated as their effects on RIF content, microsphere size, aerodynamic properties of the freeze-dried powder and in vitro release profiles. Narrowly size distributed microspheres with diameters from 2 to 8 μm, satisfactory RIF contents (from 4.9 to 16.5%), 80% RIF release from 12 h to 4 days, and adequate aerodynamic properties were prepared from a multiple emulsion and using SPG membrane pore diameter of 19.9 μm. The premix membrane homogenization appeared to be a rapid and efficient method to prepare monodisperse drug-loaded microspheres suitable for lung delivery as sustained-release microsphere aerosol.

In this paper, some analytical tools for the study of self-oscillating systems such as current-controlled static converters using pulse-width modulators are presented. These tools, based on the Tsypkin locus, concern the prediction of the switching frequency of the power stage and the characterization of its input–output behavior by an equivalent linear model. These first results, that can be used for any value of the duty cycle, are extended to the construction of the frequency response of the closed-loop system, where the power stage is replaced by a constant gain, associated with a constant time delay. This study is validated by experiments using a classical hysteresis current controller and a recent current controller without hysteresis. The obtained results are particularly useful for applications such as active filtering or high precision power supplies, where the frequency of the signal to follow can be close to one fifth of the switching frequency.

A rapid high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed for the routine quantification of colistins A and B and their prodrugs, colistin methanesulfonate (CMS) A and CMS B, respectively, in human plasma and urine by using polymyxin B1 as the internal standard (IS). CMS concentrations were determined indirectly by subtracting the colistin concentrations determined in biological samples from the whole colistin concentrations determined after sample treatment with sulfuric acid in order to hydrolyze CMS into colistin. After extraction on a solid-phase extraction column, the colistins were separated on an XBrigde C 18 column with isocratic elution (run time, 3.8 min). The mobile phase was 0.1% (vol/vol) formic acid in acetonitrile-0.1% (vol/vol) formic acid in water (20:80, vol/vol), run at a 0.2-ml/min flow rate. Ions were detected in the turbo-ion-spray-positive and multiple-reaction-monitoring modes. The ions monitored (precursor [M + 2H] 2+ to product ions) were m/z 585.5/101.2 for colistin A, m/z 578.5/101.2 for colistin B, and m/z 602.5/241.2 for IS. Prevalidation studies demonstrated the stability of CMS in biological samples and extracts, a key point for the reliable quantification of colistin and CMS. The assay was accurate and reproducible for the quantification of colistins A and B and CMSs A and B in plasma samples over concentration ranges appropriate for pharmacokinetic studies: 0.024 to 6.144, 0.015 to 3.856, 0.029 to 7.492, and 0.010 to 2.508 μg/ml, respectively. In urine samples, the assay was validated over the same concentration ranges for colistins and over concentration ranges of 0.058 to 7.492 μg/ml and 0.020 to 2.508 μg/ml for CMSs A and B, respectively.

In this paper, a particular phenomenon called indirect synchronization is investigated on self-oscillating current controllers. This phenomenon appears in medium frequencies, when the reference signal frequency tends to the switching frequency. In a previous work, it has been shown that the indirect synchronization causes discontinuities on the frequential response of the system, making the various linear or continuous models inefficient. For high-accuracy applications, such as active filtering or high-precision power supply, these discontinuities are a real problem. Thus, it seems important to offer an analytical description of this phenomenon. In this paper, an analytical model of the indirect synchronization phenomenon is proposed and checked by simulation and experimental results.

International audience; Lung administration of antibiotics by nebulization is promising for improving treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like rifampicin, cyclodextrins (CD) may improve lung delivery by permitting higher dosing. For this purpose, we investigated rifampicin-CD complexes in terms of rifampicin apparent solubility enhancement, effect on in vitro permeability on Calu-3 broncho-alveolar cells, effect on in vitro antibacterial activity against Acinetobacter baumannii and nebulization characteristics measured by NGI cascade impactor. Complexation efficiency between rifampicin and methylated beta-cyclodextrin (RAMEB) or hydroxypropyl-beta-cyclodextrin (HPbetaCD) was pH-dependent, involving the piperazin group. Rifampicin phase solubility diagrams constructed at pH 9 showed an A(L)-type curve for RAMEB and a B(S)-type for HPbetaCD. Stability constants calculated for a 1:1 molar ratio of CD/rifampicin were 73.4 +/- 8.2 M(-1) for RAMEB and 68.5 +/- 5.2 M(-1) for HPbetaCD. Complexes with RAMEB or HPbetaCD increased 22 times and 7.6 times respectively the apparent solubility of rifampicin and were found to be satisfactorily stable for 2 days when diluted in a solution at physiological pH. The nebulization of the complex solution created droplets in size range compatible with pulmonary deposition. Furthermore, the presence of HPbetaCD decreased the MMAD of the aerosolized droplets. Activity of RAMEB and HPbetaCD complexes measured by the total rifampicin MIC against A. baumannii was similar or lower to free rifampicin MIC respectively. Complexation did not alter the rifampicin permeability in the timescale of 1h as evaluated with a Calu-3 epithelial cell model, but acted as a reservoir for rifampicin. In conclusion, this work reports that CDs can be used as vectors for pulmonary nebulization to increase the amount of active rifampicin and optimize its lung pharmacokinetic profile.

This paper presents the analysis and design of a simple and effective switching frequency limitation process with sliding mode synthesis. The control scheme is based on self-oscillating phenomenon which naturally appears in relay feedback systems. Thanks to an analytical study, it shows that the maximum switching frequency of a sliding mode structure can always be limited by adding a simple second order filter in the feedback loop. To illustrate the implementation and the validity of this process, it is applied to a high dynamic voltage supply with a bandwidth of 2000 Hz and with a maximum switching frequency of 15 kHz. According to the experimental results, the switching frequency limitation process shows similar robustness properties to those of sliding mode control when the load and voltage supply change.

International audience; Ciprofloxacin (CIP) is an antibiotic that has been clinically trialed for the treatment of lung infections by aerosolisation. However, CIP is rapidly systemically absorbed after lung administration, increasing the risk for subtherapeutic pulmonary concentrations and resistant bacteria selection. In the presence of calcium, CIP forms complexes that reduce its oral absorption. Such complexation may slow down CIP absorption from the lung thereby maintaining high concentration in this tissue. Thus, we developed inhalable calcium-based inorganic-organic composite microparticles to sustain CIP within the lung. The aerodynamics and micromeritic properties of the microparticles were characterized. FTIR and XRD analysis suggest that the inorganic component of the particles comprised amorphous calcium carbonate and amorphous calcium formate, and that CIP and calcium interact in a 1:1 stoichiometry in the particles. CIP was completely released from the microparticles within 7 hours, with profiles showing a slight dependence on pH (5 and 7.4) compared to the dissolution of pure CIP. Transport studies of CIP across Calu-3 cell monolayers, in the presence of various calcium concentrations, showed a decrease of up to 84% in CIP apparent permeability. The apparent minimum inhibitory concentration of CIP against P. Aeruginosa and S. Aureus was not changed in the presence of the same calcium concentration. These results indicate that the designed particles should provide sustained levels of CIP with therapeutic effect in the lung. With these microparticles, it should be possible to control CIP pharmacokinetics within the lung, based on controlled CIP release from the particles and reduced apparent permeability across the epithelial barrier due to the cation-CIP interaction.

In this article, a design methodology applied to the case of high speed permanent magnet machines for electric vehicles is presented. The case of small power urban use vehicles is discussed. After a presentation of the analytical model used, it will be shown that, from a driving cycle, it is possible to formulate analytically the solution that maximizes the power density of the machine. Some design rules will be presented in order to optimize magnetic materials, the frequency conversion and the gear ratio.

International audience; This paper introduces an original approach of the modeling and simulation of multiphysics systems that exhibit a wide range of time scales. This approach will be illustrated by the simulation of the energy storage unit (ESU) of an all-electric ferry. The implementation of the models was performed using two different modeling approaches (causal and acausal) highlighting the main difficulties of modeling multiphysics systems. In order to optimize the sizing of the ESU considering its ageing, the system should be simulated for a lifetime of 20 years. For this purpose, a multirate method was developed to speed-up the simulation and the optimization by a factor of 100 or more.

This paper is dedicated to the optimization of the driving strategy of a high efficiency fuel cell based power train. This power train is developed to equip an urban-concept vehicle that runs energetic races where the objectives are to go the furthest with the lowest quantity of fuel (Shell Eco Marathon). Through a comprehensive dynamical model, including the mechanical requirement, the thermal behavior of the fuel cell stack and the various losses and consumption of the power train devices. This model is then integrated into a global optimization algorithm, to determine the best race strategy to be adopted (velocity profile, motor current, gearbox ratio).

A rapid and sensitive method for the determination of indinavir in mice brain and testis is described and validation data are provided. Indinavir and the internal standard (IS) amprenavir were isolated from homogenized tissue matrices using a mixed-mode solid-phase extraction (SPE) procedure and were then analyzed by reversed-phase liquid chromatography/tandem mass spectrometry (LC-MS/MS). The mass spectrometer in the positive-ion multiple reaction monitoring mode used pairs of ions at m/z of 614.1/421.3 for indinavir and of 506.1/245.3 for IS. The calibration curves were linear over the range 0.0012-0.0390 micromol/kg for brain and 0.39-12.50 micromol/kg for testis. Linearity, repeatability and accuracy were validated. The applicability of the method was demonstrated by assessing indinavir in brain and testis of three mice dosed with intravenous bolus administration of indinavir (16.3 micromol/kg).