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

Abstract basins of attraction

Abstract basins appear naturally in different areas of several complex variables. In this survey we want to describe three different topics in which they play an important role, leading to interesting open problems

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

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

Virtual screening identifies broad-spectrum \u3b2-lactamase inhibitors with activity on clinically relevant serine- and metallo-carbapenemases

Bacteria are known to evade \u3b2-lactam antibiotic action by producing \u3b2-lactamases (BLs), including carbapenemases, which are able to hydrolyze nearly all available \u3b2-lactams. The production of BLs represents one of the best known and most targeted mechanisms of resistance in bacteria. We have performed the parallel screening of commercially available compounds against a panel of clinically relevant BLs: class A CTX-M-15 and KPC-2, subclass B1 NDM-1 and VIM-2 MBLs, and the class C P. aeruginosa AmpC. The results show that all BLs prefer scaffolds having electron pair donors: KPC-2 is preferentially inhibited by sulfonamide and tetrazole-based derivatives, NDM-1 by compounds bearing a thiol, a thiosemicarbazide or thiosemicarbazone moiety, while VIM-2 by triazole-containing molecules. Few broad-spectrum BLs inhibitors were identified; among these, compound 40 potentiates imipenem activity against an NDM-1-producing E. coli clinical strain. The binary complexes of the two most promising compounds binding NDM-1 and VIM-2 were obtained at high resolution, providing strong insights to improve molecular docking simulations, especially regarding the interaction of MBLs with inhibitors

Understanding transmission and control of Cystic Echinococcosis and other taeniid infections in the Falkland Islands

Cystic echinococcosis, caused by the larval form of the cestode parasite Echinococcus granulosus, has been identified as an important public health risk in the Falkland Islands since the early 1940s. This prompted the instigation of an intensive control scheme in the mid-1960s, comprised of regular dosing of domestic dogs with the anthelmintic praziquantel and education of local people about safe disposal of potentially infected offal. This scheme has remained in place to the current day and is generally considered to be a successful programme– resulting in a reduction in the prevalence of infection in sheep has reduced from >50% in the 1950s to less than 1 % now and there has not been a case of human hydatid disease for more than 20 years. However, concerns remain that hydatid cysts are still identified in a small number of sheep at slaughter (0.004% in 2017) and occurring every year subsequently suggesting transmission is still occurring. This is also supported by the observation that sheep continue to be infected at higher levels with the (non-zoonotic) cestode Taenia hydatigena, also transmitted by dogs. In 2010, all dogs on the Falkland Islands were tested by Copro-PCR, resulting in eight dogs (1.4%) testing positive. The dog population was tested again in 2012, where there were no cases but when tested in 2014 by Coproantigen testing, six (1.04%) were positive for E. granulosus coproantigens. This project used questionnaires, coproantigen and coproPCR analysis, abattoir data surveillance, DNA sequencing, environmental sample analysis and mathematical modelling to study Echinococcus granulosus and other taeniids endemic in the Falklands and investigate how their continued transmission can occur in the face of the prolonged intensive control programme. A questionnaire survey identified possible methods of disposal of offal that in a previous study, were associated with canine coproantigen positivity. The entire dog population was analysed via coproantigen techniques in 2018, and four (0.68%) dogs were coproantigen positive, though none of these were confirmed by PCR. From 2018 to 2020, five cases of CE were identified in sheep at the Sand Bay abattoir in the Falklands (0.01%), with one of the cases coming from a positive farm in 2018. There were two cases from farms with positive dogs in 2010 and one from a farm with a positive dog in 2014. To investigate environmental contamination on farms and potentially identify historical dog infections, soil samples taken from kennel sites were analysed for the presence of coproantigens, with five farms having positive results, one farm matching with a positive dog in 2018. To identify key processes fuelling the transmission of E. granulosus in the Falklands, a mechanically informed compartmental model was created, estimating the basic reproduction number (R0) for the parasite, and identifying scenarios where this estimate increased above one suggesting continued transmission could occur. Seven scenarios where lapses in control measures could result in the R0 estimate increasing above one and continued transmission of E. granulosus could occur. The results of this project show clear evidence of dogs still being involved in the transmission of taeniid parasites in the Falklands, with key areas of the eradication programme such as the inadequate disposal of offal and dogs gaining access to offal allowing the transmission cycle to be completed and transmission of E. granulosus and other taeniids to occur. Rectifying these lapses in control measures and focussing control and surveillance to a more localised control approach will help strengthen the control programme and move the Falklands closer towards the complete eradication of Cystic Echinococcosis

The RIP140 Gene Is a Transcriptional Target of E2F1

RIP140 is a transcriptional coregulator involved in energy homeostasis and ovulation which is controlled at the transcriptional level by several nuclear receptors. We demonstrate here that RIP140 is a novel target gene of the E2F1 transcription factor. Bioinformatics analysis, gel shift assay, and chromatin immunoprecipitation demonstrate that the RIP140 promoter contains bona fide E2F response elements. In transiently transfected MCF-7 breast cancer cells, the RIP140 promoter is transactivated by overexpression of E2F1/DP1. Interestingly, RIP140 mRNA is finely regulated during cell cycle progression (5-fold increase at the G1/S and G2/M transitions). The positive regulation by E2F1 requires sequences located in the proximal region of the promoter (−73/+167), involves Sp1 transcription factors, and undergoes a negative feedback control by RIP140. Finally, we show that E2F1 participates in the induction of RIP140 expression during adipocyte differentiation. Altogether, this work identifies the RIP140 gene as a new transcriptional target of E2F1 which may explain some of the effect of E2F1 in both cancer and metabolic diseases

Selection of massive bone allografts using shape-matching 3-dimensional registration

Background and purpose Massive bone allografts are used when surgery causes large segmental defects. Shape-matching is the primary criterion for selection of an allograft. The current selection method, based on 2-dimensional template comparison, is inefficient for 3-dimensional complex bones. We have analyzed a 3-dimensional (3-D) registration method to match the anatomy of the allograft with that of the recipient