ROBOTRAN: a powerful symbolic gnerator of multibody models

The computational efficiency of symbolic generation was at the root of the emergence of symbolic multibody programs in the eighties. At present, it remains an attractive feature of it since the exponential increase in modern computer performances naturally provides the opportunity to investigate larger systems and more sophisticated models for which real-time computation is a real asset. <br><br> Nowadays, in the context of mechatronic multibody systems, another interesting feature of the symbolic approach appears when dealing with enlarged multibody models, i.e. including electrical actuators, hydraulic devices, pneumatic suspensions, etc. and requiring specific analyses like control and optimization. Indeed, since symbolic multibody programs clearly distinguish the modeling phase from the analysis process, extracting the symbolic model, as well as some precious ingredients like analytical sensitivities, in order to export it towards any suitable environment (for control or optimization purposes) is quite straightforward. Symbolic multibody model portability is thus very attractive for the analysis of mechatronic applications. <br><br> In this context, the main features and recent developments of the ROBOTRAN software developed at the Université catholique de Louvain (Belgium) are reviewed in this paper and illustrated via three multibody applications which highlight its capabilities for dealing with very large systems and coping with multiphysics issues

Anaesthetic management of people with multiple sclerosis.

There is a lack of published guidelines on the management of patients with multiple sclerosis (MS) undergoing procedures that require anaesthesia and respective advice is largely based on retrospective studies or case reports. The aim of this paper is to provide recommendations for anaesthetists and neurologists for the management of patients with MS requiring anaesthesia. This review covers issues related to the anaesthetic management of patients with MS, with a focus on preoperative assessment, choice of anaesthetic techniques and agents, side-effects of drugs used during anaesthesia and their potential impact on the disease evolution, drug interactions that may occur, and the need to use monitoring devices. A systematic PubMed research was performed to retrieve relevant articles

Relationships between Arctic sea ice drift and strength modelled by NEMO-LIM3.6

Sea ice cover and thickness have substantially decreased in the Arctic Ocean since the beginning of the satellite era. As a result, sea ice strength has been reduced, allowing more deformation and fracturing and leading to increased sea ice drift speed. We use the version 3.6 of the global ocean–sea ice NEMO-LIM model (Nucleus for European Modelling of the Ocean coupled to the Louvain-la-Neuve sea Ice Model), satellite, buoy and submarine observations, as well as reanalysis data over the period from 1979 to 2013 to study these relationships. Overall, the model agrees well with observations in terms of sea ice extent, concentration and thickness. The seasonal cycle of sea ice drift speed is reasonably well reproduced by the model. NEMO-LIM3.6 is able to capture the relationships between the seasonal cycles of sea ice drift speed, concentration and thickness, with higher drift speed for both lower concentration and lower thickness, in agreement with observations. Model experiments are carried out to test the sensitivity of Arctic sea ice drift speed, thickness and concentration to changes in sea ice strength parameter P*. These show that higher values of P* generally lead to lower sea ice deformation and lower sea ice thickness, and that no single value of P* is the best option for reproducing the observed drift speed and thickness. The methodology proposed in this analysis provides a benchmark for a further model intercomparison related to the relationships between sea ice drift speed and strength, which is especially relevant in the context of the upcoming Coupled Model Intercomparison Project 6 (CMIP6).David Docquier and Antoine Barthélemy work on the PRIMAVERA project (PRocess-based climate sIMulation: AdVances in high-resolution modelling and European climate Risk Assessment), which is funded by the European Commission’s Horizon 2020 programme, grant agreement no. 641727. François Massonnet is funded by the Belgian Fonds National de la Recherche Scientifique (FNRS) and was funded by the Ministerio de Economía, Industria y Competitividad (MINECO). Neil F. Tandon is supported by the Canadian Sea Ice and Snow Evolution (CanSISE) Network. Olivier Lecomte is a research assistant within the Belgian FNRS. The present research benefited from computational resources made available on the Tier-1 supercomputer of the Fédération Wallonie-Bruxelles, infrastructure funded by the Walloon Region under the grant agreement no. 1117545. Computational resources have also been provided by the Consortium des Équipements de Calcul Intensif (CÉCI), funded by the Fonds de la Recherche Scientifique de Belgique (F.R.S.-FNRS) under grant no. 2.5020.11. We would like to thank Hugues Goosse, Martin Vancoppenolle, Jonathan Raulier and Véronique Dansereau for their very helpful comments regarding this study. We also acknowledge Pierre-Yves Barriat for his help in using computing resources at UCL and Damien François for his advice in improving Python scripts. Finally, we thank the editor Dirk Notz and the two anonymous reviewers for helping to improve the original paper.Peer ReviewedPostprint (published version

Chemical Optimization of Selective Pseudomonas aeruginosa LasB Elastase Inhibitors and Their Impact on LasB-Mediated Activation of IL-1β in Cellular and Animal Infection Models

LasB elastase is a broad-spectrum exoprotease and a key virulence factor of Pseudomonas aeruginosa, a major pathogen causing lung damage and inflammation in acute and chronic respiratory infections. Here, we describe the chemical optimization of specific LasB inhibitors with druglike properties and investigate their impact in cellular and animal models of P. aeruginosa infection. Competitive inhibition of LasB was demonstrated through structural and kinetic studies. In vitro LasB inhibition was confirmed with respect to several host target proteins, namely, elastin, IgG, and pro-IL-1 beta. Furthermore, inhibition of LasBmediated IL-1 beta activation was demonstrated in macrophage and mouse lung infection models. In mice, intravenous administration of inhibitors also resulted in reduced bacterial numbers at 24 h. These highly potent, selective, and soluble LasB inhibitors constitute valuable tools to study the proinflammatory impact of LasB in P. aeruginosa infections and, most importantly, show clear potential for the clinical development of a novel therapy for life-threatening respiratory infections caused by this opportunistic pathogen

Spectroscopic and Mechanistic Studies of Heterodimetallic Forms of Metallo-β-lactamase NDM-1

In an effort to characterize the roles of each metal ion in metallo-β-lactamase NDM-1, heterodimetallic analogues (CoCo-, ZnCo-, and CoCd-) of the enzyme were generated and characterized. UV–vis, 1H NMR, EPR, and EXAFS spectroscopies were used to confirm the fidelity of the metal substitutions, including the presence of a homogeneous, heterodimetallic cluster, with a single-atom bridge. This marks the first preparation of a metallo-β-lactamase selectively substituted with a paramagnetic metal ion, Co(II), either in the Zn1 (CoCd-NDM-1) or in the Zn2 site (ZnCo-NDM-1), as well as both (CoCo-NDM-1). We then used these metal-substituted forms of the enzyme to probe the reaction mechanism, using steady-state and stopped-flow kinetics, stopped-flow fluorescence, and rapid-freeze-quench EPR. Both metal sites show significant effects on the kinetic constants, and both paramagnetic variants (CoCd- and ZnCo-NDM-1) showed significant structural changes on reaction with substrate. These changes are discussed in terms of a minimal kinetic mechanism that incorporates all of the data

Elastic Stable Intramedullary Nailing (ESIN), Orthoss® and Gravitational Platelet Separation - System (GPS®): An effective method of treatment for pathologic fractures of bone cysts in children

<p>Abstract</p> <p>Background</p> <p>The different treatment strategies for bone cysts in children are often associated with persistence and high recurrence rates of the lesions. The safety and clinical outcomes of a combined mechanical and biological treatment with elastic intramedullary nailing, artificial bone substitute and autologous platelet rich plasma are evaluated.</p> <p>Methods</p> <p>From 02/07 to 01/09 we offered all children with bone cysts the treatment combination of elastic intramedullary nailing (ESIN), artificial bone substitute (Orthoss^®) and autologous platelet rich plasma, concentrated by the Gravitational Platelet Separation (GPS^®) - System. All patients were reviewed radiologically for one year following the removal of the intramedullary nailing, which was possible because of cyst obliteration.</p> <p>Results</p> <p>A cohort of 12 children (4 girls, 8 boys) was recruited. The mean patient age was 11.4 years (range 7-15 years). The bone defects (ten humeral, two femoral) included eight juvenile and four aneurysmal bone cysts. Five patients suffered from persistent cysts following earlier unsuccessful treatment of humeral bone cyst after pathologic fracture; the other seven presented with acute pathologic fractures. No peri- or postoperative complications occurred. The radiographic findings showed a total resolution of the cysts in ten cases (Capanna Grade 1); in two cases a small residual cyst remained (Capanna Grade 2). The intramedullary nails were removed six to twelve months (mean 7.7) after the operation; in one case, a fourteen year old boy (Capanna Grade 2), required a further application of GPS^®and Orthoss^®to reach a total resolution of the cyst. At follow-up (20-41 months, mean 31.8 months) all patients showed very good functional results and had returned to sporting activity. No refracture occurred, no further procedure was necessary.</p> <p>Conclusions</p> <p>The combination of elastic intramedullary nailing, artificial bone substitute and autologous platelet rich plasma (GPS^®) enhances the treatment of bone cysts in children, with no resulting complications.</p