Improving realism of a surgery simulator: linear anisotropic elasticity,complex interactions and force extrapolation

In this article, we describe the latest developments of the minimally invasive hepatic surgery simulator prototype developed at INRIA. The goal of this simulator is to provide a realistic training test bed to perform laparoscopic procedures. Therefore, its main functionality is to simulate the action of virtual laparoscopic surgical instruments for deforming and cutting tridimensional anatomical models. Throughout this paper, we present the general features of this simulator including the implementation of several biomechanical models and the integration of two force‐feedback devices in the simulation platform. More precisely, we describe three new important developments that improve the overall realism of our simulator. First, we have developed biomechanical models, based on linear elasticity and finite element theory, that include the notion of anisotropic deformation. Indeed, we have generalized the linear elastic behaviour of anatomical models to ‘transversally isotropic’ materials, i.e. materials having a different behaviour in a given direction. We have also added to the volumetric model an external elastic membrane representing the ‘liver capsule’, a rather stiff skin surrounding the liver, which creates a kind of ‘surface anisotropy’. Second, we have developed new contact models between surgical instruments and soft tissue models. For instance, after detecting a contact with an instrument, we define specific boundary constraints on deformable models to represent various forms of interactions with a surgical tool, such as sliding, gripping, cutting or burning. In addition, we compute the reaction forces that should be felt by the user manipulating the force‐feedback devices. The last improvement is related to the problem of haptic rendering. Currently, we are able to achieve a simulation frequency of 25 Hz (visual real time) with anatomical models of complex geometry and behaviour. But to achieve a good haptic feedback requires a frequency update of applied forces typically above 300 Hz (haptic real time). Thus, we propose a force extrapolation algorithm in order to reach haptic real time. Copyright © 2002 John Wiley & Sons, Ltd.     

Architecture of a morphological malware detector

Most of malware detectors are based on syntactic signatures that identify known malicious programs. Up to now this architecture has been sufficiently efficient to overcome most of malware attacks. Nevertheless, the complexity of malicious codes still increase. As a result the time required to reverse engineer malicious programs and to forge new signatures is increasingly longer. This study proposes an efficient construction of a morphological malware detector, that is a detector which associates syntactic and semantic analysis. It aims at facilitating the task of malware analysts providing some abstraction on the signature representation which is based on control flow graphs. We build an efficient signature matching engine over tree automata techniques. Moreover we describe a generic graph rewriting engine in order to deal with classic mutations techniques. Finally, we provide a preliminary evaluation of the strategy detection carrying out experiments on a malware collection.     

Hybrid atomistic�Ccontinuum simulations of fluid flows involving interfaces

In this work, we use an hybrid atomistic–continuum (HAC) simulation method to study transient and steady isothermal flows of Lennard-Jones fluids near interfaces. Our hybrid method is based on a domain decomposition algorithm. The flow domain is composed of two overlapping regions: an atomistic region described by molecular dynamics, and a continuum region described by a finite volume discretization of the incompressible Navier–Stokes equations. To show the interest of such an hybrid method to compute flows near fluid/solid interface, we first applied our hybrid scheme to the classical Couette flow, where the moving wall is modelled at the atomistic scale. In addition, we also studied an oscillatory shear flow. Then, to compute flows near fluid/fluid interface, we applied our method to a two-phase Couette flow (liquid/gas), where the interface is modelled at the molecular scale. We show that hybrid results can sometimes differ from those provided by analytical solutions deduced from continuum mechanics equations combined with usual boundary/interface relations. For the Couette and oscillatory shear flows, a good agreement is found between hybrid simulations and macroscopic analytical solutions, however, we noticed that the fluid in contact with the wall can be more entailed than what expected. For the liquid/gas Couette flow, the hybrid simulation exhibits an unexpected jump of the velocity in the interfacial region, corresponding to a partial slip between the two fluid phases. Those interesting results highlight the interest of using an HAC method to deal with systems for which surfaces/interfaces effects are important.     

Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines

Isolation of bioactive products from the marine environment is considered a very promising approach to identify new compounds that can be used for further drug development. In this work we have isolated three new compounds from the purpuroine family by mass-guided preparative HPLC; purpuroine K-M. These compounds where screened for antibacterial- and antifungal activity, antibiofilm formation and anti-cell proliferation activity. Additionally, apoptosis-, cell cycle-, kinase binding- and docking studies were performed to evaluate the mechanism-of-action. None of the compounds showed activity in antibacterial-, antibiofilm- or antifungal assays. However, one of the isolated compounds, purpuroine K, showed activity against two cell lines, MV-4-11 and MOLM-13, two AML cell lines both carrying the FTL3-ITD mutation. In MV-4-11 cells, purpuroine K was found to increase apoptosis and arrest cells cycle in G1/G0, which is a common feature of FLT3 inhibitors. Interactions between purpuroine K and the FLT3 wild type or FLT3 ITD mutant proteins could however not be elucidated in our kinase binding and docking studies. In conclusion, we have isolated three novel molecules, purpuroine K-M, one of which (purpuroine K) shows a potent activity against FLT3-ITD mutated AML cell lines, however, the molecular target(s) of purpuroine K still need to be further investigated.     

Added Value of Biophysics to Study Lipid-Driven Biological Processes: The Case of Surfactins,a Class of Natural Amphiphile Molecules

The role of membrane lipids is increasingly claimed to explain biological activities of natural amphiphile molecules. To decipher this role, biophysical studies with biomimetic membrane models are often helpful to obtain insights at the molecular and atomic levels. In this review, the added value of biophysics to study lipid-driven biological processes is illustrated using the case of surfactins, a class of natural lipopeptides produced by Bacillus sp. showing a broad range of biological activities. The mechanism of interaction of surfactins with biomimetic models showed to be dependent on the surfactins-to-lipid ratio with action as membrane disturber without membrane lysis at low and intermediate ratios and a membrane permeabilizing effect at higher ratios. These two mechanisms are relevant to explain surfactins’ biological activities occurring without membrane lysis, such as their antiviral and plant immunity-eliciting activities, and the one involving cell lysis, such as their antibacterial and hemolytic activities. In both biological and biophysical studies, influence of surfactin structure and membrane lipids on the mechanisms was observed with a similar trend. Hence, biomimetic models represent interesting tools to elucidate the biological mechanisms targeting membrane lipids and can contribute to the development of new molecules for pharmaceutical or agronomic applications.     

Toward setting public health guidelines for chemicals in indoor settled dust?

Indoor settled dust may result in substantial human exposure to chemicals, especially by ingestion following hand-to-mouth or hand-to-object-to-mouth contact. As with other environmental media related to exposure, dust may thus be subject to regulation. An international scientific workshop was convened in Paris in September 2019 firstly to assess the relevance for public health of setting guidelines for indoor settled dust, and secondly to discuss scientific and technical challenges related to such guidelines. The main discussions and conclusions, with consensus achieved, are reported herein. Discussions concerned general considerations, objectives and definitions, relevance for a health-based guideline, units of measure, and finally derivation of the guideline. These points should be addressed when considering an indoor settled dust guideline as part of a policy to reduce exposure indoors to a given chemical or group of chemicals.     

Graphite nanoplatelets filled silicone composites with novel electrical and dielectric properties

In the design of medium and low voltage equipment such as cable accessories, generator, motor end windings or bushings, issues with electrical field enhancement occur at interfaces between insulators and conductors, resulting in accelerated material ageing. The purpose of this paper is to present a novel dielectric composite material which has the properties to mitigate this local amplification. It is a functional dielectric which resistivity decreases by several orders with electric field from 10¹⁴ to 10⁹ Ωm up to 1 kV?mm^?1 while the dielectric constant decreases from 15 to 12 in the 10^–2–10⁶ Hz range. This novel material is made with graphite nanoplatelets. It may be used as a resistive or capacitive field grading material in electrical applications.

     

Semisynthetic Vitamin E Derivatives as Potent Antibacterial Agents against Resistant Gram-Positive Pathogens

New 5-substituted vitamin E derivatives were semisynthesized, and their antibacterial activity against human Gram-positive and Gram-negative pathogens was evaluated. Several vitamin E analogues were active against methicillin-resistant Staphylococcus aureus (MRSA) and/or methicillin-resistant Staphylococcus epidermidis (MRSE); structure-activity relationships (SARs) are discussed. As a result, it is shown that the presence of a carboxylic acid function at the C-5 position and/or at the end of the side chain is crucial for the antibacterial activity. The bactericidal or bacteriostatic action of three compounds against MRSA and MRSE was confirmed in a time-kill kinetics study, and the cytotoxicity on human cells was evaluated. The preliminary mechanism study by confocal microscopy indicated that those vitamin E analogues led to bacterial cell death through membrane disruption.     

Simulation of boil-off losses during transfer at a LH2 based hydrogen refueling station

Losses along the LH₂ pathway are intrinsic to the utilization of a cryogenic fluid. They occur when the fluid is transferred between 2 vessels (liquefaction plant to trailer, trailer to station storage, station storage to pump or compressor, then possibly onto fuel cell electric vehicles …) and when it is warmed up due to heat transfer with the environment. Those losses can be estimated with good accuracy using thermodynamic models based on the conservation of mass and energy, provided that the thermodynamic states are correctly described. Indeed, the fluid undergoes various changes as it moves along the entire pathway (2 phase transition, sub-cooled liquid phase, super-heated warming, non-uniform temperature distributions across the saturation film) and accurate equations of state and 2 phase behavior implementations are essential. The balances of mass and energy during the various dynamics processes then enable to quantify the boil-off losses. In this work, a MATLAB code previously developed by NASA to simulate rocket loading is used as the basis for a LH₂ transfer model. This code implements complex physical phenomena such as the competition between condensation and evaporation and the convection vs. conduction heat transfer as a function of the relative temperatures on both sides of the saturated film. The original code was modified to consider real gas equations of state, and some semi-empirical relationships, such as between the heat of vaporization and the critical temperature, were replaced by a REFPROP equivalent expression, assumed to be more accurate. Non-constant liquid temperature equations were added to simulate sub-cooled conditions. The model shows that under environmental heat transfer only the liquid phase of a LH₂ vessel would experience cooling, while the boil-off is mainly a result of evaporation from the saturation film onto the vapor phase. Under the conditions assumed for this work, it was also concluded that the actual LH₂ density was lower than the corresponding saturation density given by the working pressure of the vessel. During a bottom fill transfer, for example from a LH₂ trailer to an on-site stationary vessel, it is shown that the boil-off losses are due to the compression of the vapor phase (“pdV” force). The model indicates that the magnitude of those losses is not dependent on the regulated pressure in the receiving vessel but is rather a function of the initial pressure in the vessel, amounting to more than 12% of losses for a vessel initially at 100 psia. At last, the model is used to estimate the amount of vapor H₂ vented when depressurizing a LH₂ trailer following a LH₂ delivery.