Monitor, anticipate, respond, and learn: developing and interpreting a multilayer social network of resilience abilities

Resilient performance is influenced by social interactions of several types, which may be analysed as layers of interwoven networks. The combination of these layers gives rise to a “network of networks”, also known as a multilayer network. This study presents an approach to develop and interpret multilayer networks in light of resilience engineering. Layers correspond to the four abilities of resilient systems: monitor, anticipate, respond, and learn. The proposal is applied in a 34-bed intensive care unit. To map relationships between actors in each layer, a questionnaire was devised and answered by 133 staff members, including doctors, nurses, nurse technicians, and allied health professionals. Two multilayer networks were developed: one considering that actors are 100% available and reliable (work-as-imagined) and another considering suboptimal availability and reliability (work-as-done). The multilayer networks were analysed through actor-centred (Katz centrality, degree deviation, and neighbourhood centrality) and layer-centred metrics (inter-layer correlation, and assortativity correlation). Strengths and weaknesses of social interactions at the ICU are discussed based on the adopted metrics

Influence of grape juice extraction methods on basic analytical parameters

Currently, for monitoring the ripening of grape berries, different devices are used to produce the juices to be analysed. Crushing the berries is a key step that determines the quantity of juice extracted and may impact it composition. The effect of different devices on analytical parameters of the musts produced were compared in this study. Samples from four grape varieties ('Cabernet-Sauvignon', 'Ekigaïna', 'Marselan' and 'Vermentino'), showing a variability of berry size and precocity, were crushed using six different devices (ASieves, Bag mixer®, Crusher, Manual, TPress and Blender). Whatever the pressing equipment, sugar concentrations of the must were not modified by the extraction method, unlike other parameters. pH and titratable acidity were slightly impacted by the crushing method without changing the ranking of the varieties. However, potassium concentrations were more impacted by the pressing method. Differences in mechanical forces applied to skins and seeds according to the pressing equipment used may release more or less potassium. This study clearly discarded a complete grinding of the samples for grape ripening monitoring: this method strongly modified the potassium content and, consequently, the pH and the titratable acidity of the musts

On Subexponentials, Synthetic Connectives, and Multi-level Delimited Control

International audienceWe construct a partially-ordered hierarchy of delimited control operators similar to those of the CPS hierarchy of Danvy and Filinski. However, instead of relying on nested CPS translations, these operators are directly interpreted in linear logic extended with subexponentials (i.e., multiple pairs of ! and ?). We construct an independent proof theory for a fragment of this logic based on the principle of focusing. It is then shown that the new constraints placed on the permutation of cuts correspond to multiple levels of delimited control

Modelo do processo de ação fiscal de segurança e saúde do trabalho na construção de edificações

Muitos esforços pela redução dastretanto o serviço estatal de fiscalização do cumprimento das legislações de segurança e saúde na construção de edificações seja considerado como um indutor para introdução de mudanças, seus processos operacionais pouco conhecidos. Este artigo objetiva a construção de um modelo deste processo particular de ação fiscal. Para tanto, foram realizadas entrevistas com agentes de inspeção do trabalho, gerentes de segurança e gerentes de obra, análise de documentos e acompanhamento prático de ações fiscais. Após a produção de uma versão inicial, o modelo foi revisado por um conjunto de agentes fiscais e os gerentes das empresas. O modelo construído é graficamente representado por um fluxograma do processo que descreve, em especial, um ciclo de ação fiscal, sendo constituído por planejamento das ações fiscais, visita de disparo, inspeção direta no empreendimento, resultados e possibilidade de aplicação dos instrumentos de intervenção, término e fatores favoráveis para abertura de novos ciclos. O modelo proposto tem função de organização e estruturação, embora seja limitado em descrever a variabilidade real que um ciclo fiscal pode apresentar

The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition

The Aurora B abscission checkpoint delays cytokinesis until resolution of DNA trapped in the cleavage furrow. This process involves PKCε phosphorylation of Aurora B S227. Assessing if this PKCε-Aurora B module provides a more widely exploited genome-protective control for the cell cycle, we show Aurora B phosphorylation at S227 by PKCε also occurs during mitosis. Expression of Aurora B S227A phenocopies inhibition of PKCε in by-passing the delay and resolution at anaphase entry that is associated with non-disjunction and catenation of sister chromatids. Implementation of this anaphase delay is reflected in PKCε activation following cell cycle dependent cleavage by caspase 7; knock-down of caspase 7 phenocopies PKCε loss, in a manner rescued by ectopically expressing/generating a free PKCε catalytic domain. Molecular dynamics indicates that Aurora B S227 phosphorylation induces conformational changes and this manifests in a profound switch in specificity towards S29 TopoIIα phosphorylation, a response necessary for catenation resolution during mitosis.This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001130), the UK Medical Research Council (FC001130) and the Wellcome Trust (FC001130).Peer reviewe

Mitotic catenation is monitored and resolved by a PKCε-regulated pathway.

Exit from mitosis is controlled by silencing of the spindle assembly checkpoint (SAC). It is important that preceding exit, all sister chromatid pairs are correctly bioriented, and that residual catenation is resolved, permitting complete sister chromatid separation in the ensuing anaphase. Here we determine that the metaphase response to catenation in mammalian cells operates through PKCε. The PKCε-controlled pathway regulates exit from the SAC only when mitotic cells are challenged by retained catenation and this delayed exit is characterized by BubR1-high and Mad2-low kinetochores. In addition, we show that this pathway is necessary to facilitate resolution of retained catenanes in mitosis. When delayed by catenation in mitosis, inhibition of PKCε results in premature entry into anaphase with PICH-positive strands and chromosome bridging. These findings demonstrate the importance of PKCε-mediated regulation in protection from loss of chromosome integrity in cells failing to resolve catenation in G2

An Oligopeptide Transporter of Mycobacterium tuberculosis Regulates Cytokine Release and Apoptosis of Infected Macrophages

Background: The Mycobacterium tuberculosis genome encodes two peptide transporters encoded by Rv3665c-Rv3662c and Rv1280c-Rv1283c. Both belong to the family of ABC transporters containing two nucleotide-binding subunits, two integral membrane proteins and one substrate-binding polypeptide. However, little is known about their functions in M. tuberculosis. Here we report functional characterization of the Rv1280c-Rv1283c-encoded transporter and its substrate-binding polypeptide OppA(MTB). Methodology/Principal Findings: OppA(MTB) was capable of binding the tripeptide glutathione and the nonapeptide bradykinin, indicative of a somewhat broad substrate specificity. Amino acid residues G109, N110, N230, D494 and F496, situated at the interface between domains I and III of OppA, were required for optimal peptide binding. Complementaton of an oppA knockout mutant of M. smegmatis with OppA(MTB) confirmed the role of this transporter in importing glutathione and the importance of the aforesaid amino acid residues in peptide transport. Interestingly, this transporter regulated the ability of M. tuberculosis to lower glutathione levels in infected compared to uninfected macrophages. This ability was partly offset by inactivation of oppD. Concomitantly, inactivation of oppD was associated with lowered levels of methyl glyoxal in infected macrophages and reduced apoptosis-inducing ability of the mutant. The ability to induce the production of the cytokines IL-1 beta, IL-6 and TNF-alpha was also compromised after inactivation of oppD. Conclusions: Taken together, these studies uncover the novel observations that this peptide transporter modulates the innate immune response of macrophages infected with M. tuberculosis

Studying kinetochore kinases

Mitotic kinetochores are signaling network hubs that regulate chromosome movements, attachment error-correction, and the spindle assembly checkpoint. Key switches in these networks are kinases and phosphatases that enable rapid responses to changing conditions. Describing the mechanisms and dynamics of their localized activation and deactivation is therefore instrumental for understanding the spatiotemporal control of chromosome segregation

Alteration of ribosome function upon 5-fluorouracil treatment favors cancer cell drug-tolerance.

Mechanisms of drug-tolerance remain poorly understood and have been linked to genomic but also to non-genomic processes. 5-fluorouracil (5-FU), the most widely used chemotherapy in oncology is associated with resistance. While prescribed as an inhibitor of DNA replication, 5-FU alters all RNA pathways. Here, we show that 5-FU treatment leads to the production of fluorinated ribosomes exhibiting altered translational activities. 5-FU is incorporated into ribosomal RNAs of mature ribosomes in cancer cell lines, colorectal xenografts, and human tumors. Fluorinated ribosomes appear to be functional, yet, they display a selective translational activity towards mRNAs depending on the nature of their 5'-untranslated region. As a result, we find that sustained translation of IGF-1R mRNA, which encodes one of the most potent cell survival effectors, promotes the survival of 5-FU-treated colorectal cancer cells. Altogether, our results demonstrate that "man-made" fluorinated ribosomes favor the drug-tolerant cellular phenotype by promoting translation of survival genes