The goliath project: Towards an internationally harmonised approach for testing metabolism disrupting compounds

Copyright © 2020 by the authors. The purpose of this project report is to introduce the European “GOLIATH” project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as “metabolism disrupting compounds” (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs. GOLIATH will generate the world’s first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. GOLIATH will focus on the main cellular targets of metabolic disruption—hepatocytes, pancreatic endocrine cells, myocytes and adipocytes—and using an adverse outcome pathway (AOP) framework will provide key information on MDC-related mode of action by incorporating multi-omic analyses and translating results from in silico, in vitro, and in vivo models and assays to adverse metabolic health outcomes in humans at real-life exposures. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the Organisation for Economic Development (OECD) for test method (pre-)validation, IATA, and AOP development

Towards Low Consumption Smart Dampers

International audienceCombining a feedback control strategy with tuned mass dampers is an efficient way for enhancing the capability to damp structural vibration. Several strategies have been proposed in the literature, which are targeting specific features, like multi-mode control, selective mode control. However, a comparison of these concepts based on objective criteria is missing, although very important for detecting shortcomings, and limitations in practical implementations. The objective of this paper is to investigate an extensive comparison of three concepts of active damper, namely the dual loop controllers, Alpha-HMD and Hybrid-Double-TMD. This comparison will encompass criteria like stability margins, bandwidth, transducer stroke, maximum force, or power consumption

Phase compensator for hyperstable hybrid mass

International audienc

Phase compensator for hyperstable hybrid mass

International audienc

Enhanced Damping of Flexible Structures Using Force Feedback

International audienceDuring the last three decades, several active damping strategies have been proposed, based on the so-called passivity concept, or equivalently, on the power port concept. One of them, known as Integral Force Feedback (IFF) is reviewed in this paper. Actually, the main drawback of the IFF is that high active damping is obtained at the cost of a degradation of the compliance at low frequency, compromising the capability of disturbance rejection. Classically, a trade-off between damping and stiffness can be reached by adequately high pass filtering the control signal. However, the high pass filter poles and zeros often interfere with the plant dynamics, which in turn compromises the guaranteed stability of the IFF. In this paper, a novel type of high pass filter is proposed. It is shown that this modification makes the controller unconditionally stable, and increases drastically the achievable modal damping. Analytic formulas are derived, and illustrated using simple numerical models. The characteristics of the proposed controller are discussed in terms of maximum modal damping and transmissibility

On the passivity concept to design hybrid tuned mass damper

peer reviewe

Hybrid Electromagnetic Shunt Damper for Vibration Control

It has been shown that shunting electromagnetic devices with electrical networks can be used to damp vibrations. These absorbers have however limitations that restrict the control performance, i.e., the total damping of the system and robustness versus parameter variations. On the other hand, the electromagnetic devices are widely used in active control techniques as an actuator. The major difficulty that arises in practical implementation of these techniques is the power consumption required for conditioners and control units. In this study, robust hybrid control system is designed to combine the passive electromagnetic shunt damper with an active control in order to improve the performance with low power consumption. Two different active control laws, based on an active voltage source and an active current source, are proposed and compared. The control law of the active voltage source is the direct velocity feedback. However, the control law of the active current source is a revisited direct velocity feedback. The method of maximum damping, i.e., maximizing the exponential time-decay rate of the response subjected to the external impulse forcing function, is employed to optimize the parameters of the passive and the hybrid control systems. The advantage of using the hybrid control configuration in comparison with purely active control system is also investigated in terms of the power consumption. Besides these assets, it is demonstrated that the hybrid control system can tolerate a much higher level of uncertainty than the purely passive control systems. © 2020 by ASME

Optimization of the HepaRG cell model for drug metabolism and toxicity studies.

International audienceThe HepaRG cell line is the first human cell line able to differentiate in vitro into mature hepatocyte-like cells. Our main objective within the framework of the EEC-LIINTOP project was to optimize the use of this cell line for drug metabolism and toxicity studies, especially after repeat treatments. The main results showed that differentiated HepaRG cells: (i) retained their drug metabolism capacity (major CYPs, phase 2 enzymes, transporters and nuclear receptors) and responsiveness to prototypical inducers at relatively stable levels for several weeks at confluence. The levels of several functions, including some CYPs such as CYP3A4, were dependent on the addition of dimethyl sulfoxide in the culture medium; (ii) sustained the different types of chemical-induced hepatotoxicity, including steatosis, phospholipidosis and cholestasis, after acute and/or repeat treatment with reference drugs. In particular, drug-induced vesicular steatosis was demonstrated in vitro for the first time. In conclusion, our results from the LIINTOP project, together with other studies reported concomitantly or more recently in the literature, support the conclusion that the metabolically competent human HepaRG cells represent a surrogate to primary human hepatocytes for investigating drug metabolism parameters and both acute and chronic effects of xenobiotics in human liver

Design and optimization of a novel resonant control law using force feedback for vibration mitigation

Integral-force-feedback (IFF) is a popular control law in active vibration damping of mechanical system when a force sensor is collocated with a force actuator. While it is simple, robust to resonance uncertainty and stable for any feedback gains, its efficiency is limited by system's parameters and in particular the stiffness ratio between the structure and the actuator. Therefore, the control authority decreases at high frequency resonances or when the actuator is weakly coupled to the structure. It has been shown that the use of double integrator with a real zero, named α-controller, can improve the control authority of a target mode. However, this technique like IFF cannot be easily implemented in practice because of low frequency saturation issue induced by significantly amplifying the low frequency content during the integration process. This paper proposes a new control law, named resonant-force-feedback (RFF), based on a second order low pass filter to damp a target mode resonance. Through the mechanical analogy of the proposed system, RFF can be seen as an active realization of an inerter-spring-damper (ISD) system. In addition, the parameters of RFF are optimized based on two methods, that is, maximum damping criterion and H∞ optimization which consists in minimizing the settling time of the impulse response and the peak amplitude in the frequency domain, respectively. It is shown that RFF always provides a higher control authority of a target mode in comparison to IFF for a given stiffness ratio and in particular when the stiffness ratio is low. Despite the fact that the performance of the system, in terms of the closed-loop damping ratio or the amplitude reduction, obtained by RFF is very close to that of α-controller, RFF requires less control effort in comparison to α-controller. The stability of the proposed system is also assessed in terms of the gain margin and the phase margin although the system is unconditionally stable. Moreover, the robustness of the designed RFF is compared to that of IFF under stiffness uncertainty. Although IFF can tolerate a higher level of uncertainty, the performance of RFF is superior to that of IFF for almost 50% of changes in the stiffness of the primary system.SCOPUS: ar.jinfo:eu-repo/semantics/publishe