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

Expanding the Repertoire of Carbapenem-Hydrolyzing Metallo-ß-Lactamases by Functional Metagenomic Analysis of Soil Microbiota

Carbapenemases are bacterial enzymes that hydrolyze carbapenems, a group of last-resort β-lactam antibiotics used for treatment of severe bacterial infections. They belong to three β-lactamase classes based amino acid sequence (A, B, and D). The aim of this study was to elucidate occurrence, diversity and functionality of carbapenemase-encoding genes in soil microbiota by functional metagenomics. Ten plasmid libraries were generated by cloning metagenomic DNA from agricultural (n = 6) and grassland (n = 4) soil into Escherichia coli. The libraries were cultured on amoxicillin-containing agar and up to 100 colonies per library were screened for carbapenemase production by CarbaNP test. Presumptive carbapenemases were characterized with regard to DNA sequence, minimum inhibitory concentration (MIC) of β-lactams, and imipenem hydrolysis. Nine distinct class B carbapenemases, also known as metallo-beta-lactamases (MBLs), were identified in six soil samples, including two subclass B1 (GRD23-1 and SPN79-1) and seven subclass B3 (CRD3-1, PEDO-1, GRD33-1, ESP-2, ALG6-1, ALG11-1, and DHT2-1). Except PEDO-1 and ESP-2, these enzymes were distantly related to any previously described MBLs (33 to 59% identity). RAIphy analysis indicated that six enzymes (CRD3-1, GRD23-1, DHT2-1, SPN79-1, ALG6-1, and ALG11-1) originated from Proteobacteria, two (PEDO-1 and ESP-2) from Bacteroidetes and one (GRD33-1) from Gemmatimonadetes. All MBLs detected in soil microbiota were functional when expressed in E. coli, resulting in detectable imipenem-hydrolyzing activity and significantly increased MICs of clinically relevant β-lactams. Interestingly, the MBLs yielded by functional metagenomics generally differed from those detected in the same soil samples by antibiotic selective culture, showing that the two approaches targeted different subpopulations in soil microbiota. © 2016 Gudeta, Bortolaia, Pollini, Docquier, Rossolini, Amos, Wellington and Guardabassi.Grant HEALTH-F3-2011-282004(EvoTAR

A general theory to estimate Information transfer in nonlinear systems

A general theory for computing information transfers in nonlinear systems driven by deterministic forcings and additive and/or multiplicative noises, is presented. It extends the Liang-Kleeman framework of causality inference based on information transfer across system variables (Liang, 2016). An effective method of computing formulas of the rates of entropy transfers (RETs) is presented, the Causal Sensitivity Method (CSM), relying on the estimation from data of conditional expectations. Those expectations are approximated by nonlinear regressions, leading to a much easier and more robust way of computing RETs than the brute-force approach calling for numerical integrals over the phase space and the knowledge of the multivariate probability density function of the system. The CSM is furthermore fully adapted to the case where no model equations are available, starting with a nonlinear model fitting from data with the subsequent application of CSM to the fitted model. Moreover, the RETs are decomposed into sums of single one-to-one RETs plus synergetic terms, accounting for the joint causal effect of groups of variables. State-dependent RET formulas are also proposed, allowing for determining the dependencies of variables and synergies locally in phase space. A comparison of the RETs estimations is performed between the brute-force probability-density-based approach (AN), the CSM-based approach with and/or without model fitting, and the multivariate linear approach, in the context of two models: (i) a model derived from a potential and (ii) the classical chaotic Lorenz system, both forced by additive and/or multiplicative noises. The analysis demonstrates that the CSM estimations are robust and close to the AN-reference values in the different experiments, providing evidence of the possibilities offered by the method and opening new perspectives on real-world applications.Comment: 41 pages, 6 figures. Submitted to Physica

Causal dependencies and Shannon entropy budget -- Analysis of a reduced order atmospheric model

The information entropy budget and the rate of information transfer between variables is studied in the context of a nonlinear reduced-order atmospheric model. The key ingredients of the dynamics are present in this model, namely the baroclinic and barotropic instabilities, the instability related to the presence of an orography, the dissipation related to the surface friction, and the large-scale meridional imbalance of energy. For the parameter chosen, the solutions of this system display a chaotic dynamics reminiscent of the large-scale atmospheric dynamics in the extra-tropics. The detailed information entropy budget analysis of this system reveals that the linear rotation terms plays a minor role in the generation of uncertainties as compared to the orography and the surface friction. Additionally, the dominant contribution comes from the nonlinear advection terms, and their decomposition in synergetic (co-variability) and single (impact of each single variable on the target one) components reveals that for some variables the co-variability dominates the information transfer. The estimation of the rate of information transfer based on time series is also discussed, and an extension of the Liang's approach to nonlinear observables, is proposed.Comment: 26 pages, 11 figures, 5 table

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

Migration Costs and Networks: household optimal investment in migration

International migration is an expensive form of investment, that only households relatively better off can afford. However poorer households have the higher incentive to migrate. Migration decision is conditional on the entry cost, expected returns and risks of migration. This paper, using data from Mexican rural and urban areas, examines the relation between household and community networks and costs and risks of migration focusing on the optimal investment in migration. To investigate an household optimal number of migrants this paper introduces a Three Step procedure to solve simultaneously for the endogeneity of network size and possible selection of migrants. The analysis confirms the inverted U-shaped relation between wealth and migration, stressing the importance of networks particularly in facilitating the migration of social strata belonging to the left tail of the income distribution. Moreover, in presence of sunk costs and/or high initial investment, household and community networks accomplish different functions

Multidrug-resistant Pseudomonas aeruginosa producing PER-1 extended-spectrum serine-beta-lactamase and VIM-2 metallo-beta-lactamase.

[No abstract available]Europena Training and Mobility of Researchers Network on Metallo-beta-Lactamases (grant no. FMRX-CT98-0232

Regulation of the apoptotic genes in breast cancer cells by the transcription factor CTCF

CTCF is a highly conserved and ubiquitous transcription factor with versatile functions. We previously demonstrated that elevated protein levels of CTCF in breast cancer cells were associated with the specific anti-apoptotic function of CTCF. We used proteomics and microarray approaches to identify regulatory targets of CTCF specific for breast cancer cells. Among the CTCF identified targets were proteins involved in the control of apoptosis. A proapoptotic protein, Bax, negatively regulated by CTCF, was chosen for further investigation. Repression of the human Bax gene at the transcriptional level by CTCF in breast cancer cells was confirmed by real-time PCR. Two CTCF binding sites within the Bax promoter were identified by electrophoretic mobility shift assay and footprinting. In reporter assays, the Bax-luciferase reporter construct, containing CTCF-binding sites, was negatively regulated by CTCF. In vivo, CTCF occupied its binding sites in breast cancer cells and tissues, as confirmed by chromatin immunoprecipitation assay. Our findings suggest a possible mechanism of the specific CTCF anti-apoptotic function in breast cancer cells whereby CTCF is bound to the Bax promoter, resulting in repression of Bax and inhibition of apoptosis; depletion of CTCF leads to activation of Bax and apoptotic death. CTCF binding sites in the Bax promoter are unmethylated in all cells and tissues inspected. Therefore, specific CTCF interaction with the Bax promoter in breast cancer cells, and the functional outcome, may depend on a combination of epigenetic factors characteristic for these cells. Interestingly, CTCF appears to be a negative regulator of other proapoptotic genes (for example, Fas, Apaf-1, TP531NP1). Conversely, stimulating effects of CTCF on the anti-apoptotic genes (Bcl-2, Bag-3) have been observed. Taken together, these findings suggest that specific mechanisms have evolved in breast cancer cells to protect them from apoptosis; regulation of apoptotic genes by CTCF appears to be one of the resistance strategies

Determinants and consequences of international migration

This chapter provides a simple overview of the canonical model of international migration, discusses the consequences of migration on both sending and receiving countries and draws some considerations on future research prospects for the international migration literature