Scaling properties of work fluctuations after quenches at quantum transitions

We study the scaling properties of the statistics of the work done on a generic many-body system at a quantum phase transition of any order and type, arising from quenches of a driving control parameter. For this purpose we exploit a dynamic finite-size scaling framework. Namely, we put forward the existence of a nontrivial finite-size scaling limit for the work distribution, defined as the large-size limit when appropriate scaling variables are kept fixed. The corresponding scaling behaviors are thoroughly verified by means of analytical and numerical calculations in two paradigmatic many-body systems as the quantum Ising model and the Bose-Hubbard model.Comment: 30 pages, 6 figures. Revised versio

Contributions to Soft Microrobotics :Advanced Kinematics Based on Digital Manufacturing of Active Materials and Pneumatic Actuation for Endoscopy

This thesis studies soft microrobotics actuation solutions for the generation of complex motions in thecontext of medical and endoscopic applications. Flexible endoscopy requires flexible and steerable toolsto perform medical interventions through the natural orifices. It could benefit from soft and dexterousactuators with multiple degrees of freedom to ensure patient safety while navigating tortuous pathways.To this end, the rise of soft actuation, using stimuli-responsive materials of similar softness as biologicaltissues opens new opportunities. This thesis investigates the potential of three soft actuation solutionsto generate complex deformations (deformations beyond pure elongation, compression, shear, twist orbending) while assessing their potential in terms of miniaturization, safety, and mechanical capabilitiesfor future use in medical applications. Firstly, a 6mm diameter pneumatic actuator for endoscopyis designed, implemented, and characterized. It bends in every direction and incorporates a workingchannel. A vacuum centrifugal overmolding method capable of producing small geometries with a varietyof silicones is described, and meter-long actuators are extruded industrially. The actuator achievesbending of more than 180° and curvatures of up to 0.1mm–1. The exerted force remains below 100mN,and with no rigid parts in the design, it limits the risks of damage to surrounding tissues. The responsetime below 300 ms is not limiting for medical applications. An 85 cm long steerable catheter carryingan optical fiber is demonstrated in a bronchial tree phantom. To generate more complex motions,and further from the medical application, a voxel-based approach is proposed from the literaturereview. This methodology is based on the decomposition of complex motions into active buildingblocks, called voxels, each able of a given basic kinematic. Designs are presented to build these voxelsusing only an active isotropically expansive or compressive material, reinforced adequately by a passive(or less expansive) material. This approach is first implemented using heat actuated Phase-ChangeMaterial–Elastomer Composite (PCMEC)-based expansive actuators. Centimetric kirigami-inspiredpaper reinforced voxels are modeled, built and characterized. All basic kinematics can be obtained.Additionally, a manufacturing method to use different fluid–elastomer combinations without alteringthe quality of the samples is proposed. This allows PCMEC to be used safely in contact with humanbodies, by using fluids with a low boiling point (as low as 34°C). The voxel-based methodology is thenimplemented at the micrometer scale using shrinking pNIPAM hydrogel-based actuators. A digitalfabrication method (two-photon polymerization) is adapted to build patterned structures in a one-stepprocess. Voxels able of bending, compression, and twisting are built and assembled. The influence ofthe exposure dose and temperature on the pNIPAM actuation strain is characterized. Curvature up to10 mm–1 is measured. Even if far from any application, the demonstrated structures would be difficultto achieve at this scale with another strategy, and the versatility of the voxel-based approach makes itadaptable to a large variety of motions. This thesis is supervised by prof. Alain Delchambre in theBEAMS department and prof. Pierre Lambert in the TIPs department.Doctorat en Sciences de l'ingénieur et technologieinfo:eu-repo/semantics/nonPublishe

A Soft Pneumatic Two-Degree-of-Freedom Actuator for Endoscopy

The rise of soft robotics opens new opportunities in endoscopy and minimally invasive surgery. Pneumatic catheters offer a promising alternative to conventional steerable catheters for safe navigation through the natural pathways without tissue injury. In this work, we present an optimized 6 mm diameter two-degree-of-freedom pneumatic actuator, able to bend in every direction and incorporating a 1 mm working channel. A versatile vacuum centrifugal overmolding method capable of producing small geometries with a variety of silicones is described, and meter-long actuators are extruded industrially. An improved method for fiber reinforcement is also presented. The actuator achieves bending more than 180° and curvatures of up to 0.1 mm −1 .The exerted force remains below 100 mN, and with no rigid parts in the design, it limits the risks of damage on surrounding tissues. The response time of the actuator is below 300 ms and therefore not limited for medical applications. The working space and multi-channel actuation are also experimentally characterized. The focus is on the study of the influence of material stiffness on mechanical performances. As a rule, the softer the material, the better the energy conversion, and the stiffer the material, the larger the force developed at a given curvature. Based on the actuator, a 90 cm long steerable catheter demonstrator carrying an optical fiber is developed, and its potential for endoscopy is demonstrated in a bronchial tree phantom. In conclusion, this work contributes to the development of a toolbox of soft robotic solutions for MIS and endoscopic applications, by validating and characterizing a promising design, describing versatile and scalable fabrication methods, allowing for a better understanding of the influence of material stiffness on the actuator capabilities, and demonstrating the usability of the solution in a potential use-case.info:eu-repo/semantics/publishe

Study of a Miniaturized Soft Bending Actuator for Surgical Endoscopy

info:eu-repo/semantics/nonPublishe

Methodological Integration of Sustainability in the Design Process of Medical Devices: A Case Study on EEG Electrodes

info:eu-repo/semantics/nonPublishe

Mutations on VEEV nsP1 relate RNA capping efficiency to ribavirin susceptibility

International audienceAlphaviruses are arthropod-borne viruses of public health concern. To date no efficient vaccine nor antivirals are available for safe human use. During viral replication the nonstructural protein 1 (nsP1) catalyzes capping of genomic and subgenomic RNAs. The capping reaction is unique to the Alphavirus genus. The whole three-step process follows a particular order: (i) transfer of a methyl group from S-adenosyl methionine (SAM) onto a GTP forming m7GTP; (ii) guanylylation of the enzyme to form a m7GMP-nsP1adduct; (iii) transfer of m7GMP onto 5′-diphosphate RNA to yield capped RNA. Specificities of these reactions designate nsP1 as a promising target for antiviral drug development. In the current study we performed a mutational analysis on two nsP1 positions associated with Sindbis virus (SINV) ribavirin resistance in the Venezuelan equine encephalitis virus (VEEV) context through reverse genetics correlated to enzyme assays using purified recombinant VEEV nsP1 proteins. The results demonstrate that the targeted positions are strongly associated to the regulation of the capping reaction by increasing the affinity between GTP and nsP1. Data also show that in VEEV the S21A substitution, naturally occurring in Chikungunya virus (CHIKV), is a hallmark of ribavirin susceptibility. These findings uncover the specific mechanistic contributions of these residues to nsp1-mediated methyl-transfer and guanylylation reactions

Discovery of novel dengue virus NS5 methyltransferase non-nucleoside inhibitors by fragment-based drug design

International audienc

Programmable Stimuli-Responsive Actuators for Complex Motions in Soft Robotics: Concept, Design and Challenges

During the last years, great progress was made in material science in terms of concept, design and fabrication of new composite materials with conferred properties and desired functionalities. The scientific community paid particular interest to active soft materials, such as soft actuators, for their potential as transducers responding to various stimuli aiming to produce mechanical work. Inspired by this, materials engineers today are developing multidisciplinary approaches to produce new active matters, focusing on the kinematics allowed by the material itself more than on the possibilities offered by its design. Traditionally, more complex motions beyond pure elongation and bending are addressed by the robotics community. The present review targets encompassing and rationalizing a framework which will help a wider scientific audience to understand, sort and design future soft actuators and methods enabling complex motions. Special attention is devoted to recent progress in developing innovative stimulus-responsive materials and approaches for complex motion programming for soft robotics. In this context, a challenging overview of the new materials as well as their classification and comparison (performances and characteristics) are proposed. In addition, the great potential of soft transducers are outlined in terms of kinematic capabilities, illustrated by the related application. Guidelines are provided to design actuators and to integrate asymmetry enabling motions along any of the six basic degrees of freedom (translations and rotations), and strategies towards the programming of more complex motions are discussed. As a final note, a series of manufacturing methods are described and compared, from molding to 3D and 4D printing. The review ends with a Perspectives section, from material science and microrobotic points of view, on the soft materials’ future and close future challenges to be overcome.info:eu-repo/semantics/publishe

Optimization of Phase-Change Material–Elastomer Composite and Integration in Kirigami-Inspired Voxel-Based Actuators

Phase-change material–elastomer composite (PCMEC) actuators are composed of a soft elastomer matrix embedding a phase-change fluid, typically ethanol, in microbubbles. When increasing the temperature, the phase change in each bubble induces a macroscopic expansion of the matrix. This class of actuators is promising for soft robotic applications because of their high energy density and actuation strain, and their low cost and easy manufacturing. However, several limitations must be addressed, such as the high actuation temperature and slow actuation speed. Moreover, the lack of a consistent design approach limits the possibility to build PCMEC-based soft robots able to achieve complex tasks. In this work, a new approach to manufacture PCMEC actuators with different fluid–elastomer combinations without altering the quality of the samples is proposed. The influence of the phase-change fluid and the elastomer on free elongation and bending is investigated. We demonstrate that choosing an appropriate fluid increases the actuation strain and speed, and decreases the actuation temperature compared with ethanol, allowing PCMECs to be used in close contact with the human body. Similarly, by using different elastomer materials, the actuator stiffness can be modified, and the experimental results showed that the curvature is roughly proportional to the inverse of Young’s modulus of the pure matrix. To demonstrate the potential of the optimized PCMECs, a kirigami-inspired voxel-based design approach is proposed. PCMEC cubes are molded and reinforced externally by paper. Cuts in the paper induce anisotropy into the structure. Elementary voxels deforming according to the basic kinematics (bending, torsion, elongation, compression and shear) are presented. The combination of these voxels into modular and reconfigurable structures could open new possibilities towards the design of flexible robots able to perform complex tasks.info:eu-repo/semantics/publishe

Optimization of a fragment linking hit toward Dengue and Zika virus NS5 methyltransferases inhibitors

International audienceNo antiviral drugs to treat or prevent life-threatening flavivirus infections such as those caused by mosquito-borne Dengue (DENV) and more recently Zika (ZIKV) viruses are yet available. We aim to develop, through a structure-based drug design approach, novel inhibitors targeting the NS5 AdoMet-dependent mRNA methyltransferase (MTase), a viral protein involved in the RNA capping process essential for flaviviruses replication. Herein, we describe the optimization of a hit (5) identified using fragment-based and structure-guided linking techniques, which binds to a proximal site of the AdoMet binding pocket. X-ray crystallographic structures and computational docking were used to guide our optimization process and lead to compounds 30 and 33 (DENV IC50 = 26 μM and 23 μM; ZIKV IC50 = 28 μM and 19  μM, respectively), two representatives of novel non-nucleoside inhibitors of flavivirus MTases