Sarah Kane and Cleansed: projecting life on stage

Neste artigo analisaremos a peça teatral Purificados da dramaturga inglesa Sarah Kane, bem como a sua vida pessoal que entrecruza com as personagens no palco. O espetáculo apresenta histórias distintas de seis vítimas e de um sádico omnipotente que faz deles os “prisioneiros” de uma instituição. O espaço de encenação lembra um hospital/campus hiper-real com traços de centro de detenção onde os irmãos incestuosos, um casal homossexual, um jovem/utente perturbado e uma dançarina de peep-show tentam sobreviver. A peça levanta problemas de intolerância social e transgeneridade, de violência física e consumo de substâncias nocivas. Numa atmosfera de despiedade os jovens resistem ao castigo, manifestando o afeto pelos seus entes queridos.In this article, we will analyse Sarah Kane’s play Cleansed reading in it expressions of her personal life, as they are intertwined with characters on stage. The performance features different stories of six victims and an omnipotent sadist who makes them the “prisoners” of some unspecified institution. The set resembles a hyperreal hospital / campus with features of a detention centre where siblings in an incestuous relationship, a homosexual couple, a disturbed young man and a peep-show dancer try to survive. The play raises problems of social intolerance and transgenderism, physical violence and consumption of harmful substances. In an atmosphere of deprivation, young people resist punishment, showing affection for their loved ones

A escrita pós-modernista em Se Numa Noite De Inverno Um Viajante, de Italo Calvino

O objetivo do presente artigo é delinear os princípios e métodos que distinguem uma obra literária pós-modernista. O caso prático consiste na análise dos meios estilísticos utilizados por Italo Calvino, no seu romance Se Numa Noite de Inverno um Viajante, que transformaram esta obra num exemplo de literatura pós-moderna. A fundamentação teórica assenta, nomeadamente, nos conceitos sobre pós-modernismo de Jean Baudrillard, Ihab Hassan, Matei Calinescu e David Damrosch. O romance, escrito em forma de narrativa não linear, abrange dez histórias estilisticamente diferentes que terminam de repente no seu ponto culminante. Por meio das ferramentas pós-modernistas, Calvino desconstrói a narrativa conceitual, substituindo-a por uma estrutura textual complexa, ao mesmo tempo ambígua e cativante. Neste exercício de estilo, Calvino exemplifica quais são os modelos e os tipos do romance moderno (do neorrealismo ao surrealismo, passando pela literatura fantástica e neovanguardista) e apresenta, em forma de metanarrativa, a sua conceção de romance, enquanto jogo combinatório de palavras, em que a realidade é substituída pelo universo linguístico. Um texto seria, assim, a passagem do mundo das coisas, ao mundo das palavras, do mundo vivido, ao verbal; em suma, do mundo não-escrito ao mundo escrito – como lugar literário por excelência.The purpose of this paper is to outline the principles and methods that distinguish a postmodern literary work. The case study is based on the analysis of the stylistic tools used by Italo Calvino in his famous novel, If on a Winter's Night a Traveller, that turned this work into an example of postmodern literature. The theoretical fundaments are namely based on the concepts of postmodernism by Jean Baudrillard, Ihab Hassan, Matei Calinescu and David Damrosch. If on a Winter's Night a Traveller, written in a nonlinear narrative form, includes ten stylistically different stories that terminate suddenly at their climax. By means of postmodern tools, Calvino deconstructs a conceptual narrative, replacing it with a complex textual structure that is ambiguous and engaging at the same time. In this stylistic exercise Calvino exemplifies the models and types of the modern novel (from neorealism to surrealism, through fantasy and neo-avant-garde literature) and presents in a metanarrative form his conception of the novel as a combinatory game of words in which reality is replaced by the linguistic universe. A text would thus be the passage from the world of things to the world of words, from the living world to the verbal one; in short, from the unwritten world to the written world – as a literary place par excellence.info:eu-repo/semantics/publishedVersio

Polarization Switching Between Electric and Magnetic Quasi-Trapped Modes in Bianisotropic All-Dielectric Metasurfaces

A general strategy for the realization of electric and magnetic quasi-trapped modes located at the same spectral position is presented. This strategy's application makes it possible to design metasurfaces allowing switching between the electric and magnetic quasi-trapped modes by changing the polarization of the incident light wave. The developed strategy is based on two stages: the application of the dipole approximation for determining the conditions required for the implementation of trapped modes at certain spectral positions and the creation of the energy channels for their excitation by introducing a weak bianisotropy in nanoparticles. Since excitation of trapped modes results in a concentration of electric and magnetic energies in the metasurface plane, the polarization switching provides possibilities to change and control the localization and distribution of optical energy at the sub-wavelength scale. A practical method for spectral tuning of quasi-trapped modes in metasurfaces composed of nanoparticles with a preselected shape is demonstrated. As an example, the optical properties of a metasurface composed of silicon triangular prisms are analyzed and discussed

СТАТИСТИЧЕСКИЙ ПОДХОД К ОЦЕНКЕ ЛОГИСТИЧЕСКИХ РИСКОВ ПРОМЫШЛЕННЫХ ПРЕДПРИЯТИЙ

The article offers the methodology of statistical research of the risks of logistical systems to improve the stability and efficiency of Russian industrial enterprises. Realization of this methodology is shown by the example of estimation of the risks of late shipment of goods of OAO Magnitogorsk Iron and Steel Works, JSC.В статье предложена методика статистического исследования рисков логистических систем для повышения устойчивости и эффективности работы промышленных предприятий России. Реализация данной методики продемонстрирована на примере оценки риска несвоевременной отгрузки продукции ОАО «Магнитогорский металлургический комбинат»

Astrocytes promote progression of breast cancer metastases to the brain via a KISS1-mediated autophagy.

Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and protein levels. By using multicolor immunofluorescence and coculture techniques here we show that normal adult astrocytes in the brain are capable of promoting metastatic transformation of circulating breast cancer cells localized to the brain through secretion of chemokine CXCL12. The latter was found in this study to downregulate KISS1 expression at the post-transcriptional level via induction of microRNA-345 (MIR345). Furthermore, we demonstrated that ectopic expression of KISS1 downregulates ATG5 and ATG7, 2 key modulators of autophagy, and works concurrently with autophagy inhibitors, thereby implicating autophagy in the mechanism of KISS1-mediated BrCa metastatic transformation. We also found that expression of KISS1 in human breast tumor specimens inversely correlates with that of MMP9 and IL8, implicated in the mechanism of metastatic invasion, thereby supporting the role of KISS1 as a potential regulator of BrCa metastatic invasion in the brain. This conclusion is further supported by the ability of KISS1, ectopically overexpressed from an adenoviral vector in MDA-MB-231Br cells with silenced expression of the endogenous gene, to revert invasive phenotype of those cells. Taken together, our results strongly suggest that human adult astrocytes can promote brain invasion of the brain-localized circulating breast cancer cells by upregulating autophagy signaling pathways via the CXCL12-MIR345- KISS1 axis

VID22 counteracts G-quadruplex-induced genome instability

Genome instability is a condition characterized by the accumulation of genetic alterations and is a hallmark of cancer cells. To uncover new genes and cellular pathways affecting endogenous DNA damage and genome integrity, we exploited a Synthetic Genetic Array (SGA)-based screen in yeast. Among the positive genes, we identified VID22, reported to be involved in DNA double-strand break repair. vid22Δ cells exhibit increased levels of endogenous DNA damage, chronic DNA damage response activation and accumulate DNA aberrations in sequences displaying high probabilities of forming G-quadruplexes (G4-DNA). If not resolved, these DNA secondary structures can block the progression of both DNA and RNA polymerases and correlate with chromosome fragile sites. Vid22 binds to and protects DNA at G4-containing regions both in vitro and in vivo. Loss of VID22 causes an increase in gross chromosomal rearrangement (GCR) events dependent on G-quadruplex forming sequences. Moreover, the absence of Vid22 causes defects in the correct maintenance of G4-DNA rich elements, such as telomeres and mtDNA, and hypersensitivity to the G4-stabilizing ligand TMPyP4. We thus propose that Vid22 is directly involved in genome integrity maintenance as a novel regulator of G4 metabolism.Associazione Italiana per la Ricerca sul Cancro (AIRC) [15631, 21806 to M.M.F.]; MIUR [PRIN 2015-2015SJLMB9; PRIN 2017-2017KSZZJW to M.M.F.]; Telethon [GGP15227 to M.M.F.]; F.L. was supported by the University of Milano: ‘‘Piano di Sviluppo dell’Ateneo per la Ricerca. Linea B: Supporto per i Giovani Ricercatori’’; M.C.B. was supported by Fondazione Veronesi; Research at the laboratory of A.A. was funded by the Spanish Ministry of Economy and Competitiveness [BFU2016-75058-P]; B.G.G. was funded by the Spanish Association Against Cancer; MIUR [PRIN2017-2017Z55KC to T.B.]; M.C., D.S.H. are supported by MIUR [PRIN 2017] and CNRbiomics [PIR01_00017]; H2020 Projects ELIXIR-EXCELERATE, EOSC-Life, EOSC-Pillar and Elixir-IIB; G.W.B. was supported by the Canadian Institutes of Health Research[FDN-159913]. Funding for open access charge: Associazione Italiana per la Ricerca sul Cancro (AIRC) [21806]

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

STATISTICAL APPROACH TO ESTIMATION OF LOGISTICAL RISKS OF INDUSTRIAL ORGANIZATIONS

The article offers the methodology of statistical research of the risks of logistical systems to improve the stability and efficiency of Russian industrial enterprises. Realization of this methodology is shown by the example of estimation of the risks of late shipment of goods of OAO Magnitogorsk Iron and Steel Works, JSC

Next-Generation Theranostic Agents Based on Polyelectrolyte Microcapsules Encoded with Semiconductor Nanocrystals: Development and Functional Characterization

Abstract Fabrication of polyelectrolyte microcapsules and their use as carriers of drugs, fluorescent labels, and metal nanoparticles is a promising approach to designing theranostic agents. Semiconductor quantum dots (QDs) are characterized by extremely high brightness and photostability that make them attractive fluorescent labels for visualization of intracellular penetration and delivery of such microcapsules. Here, we describe an approach to design, fabricate, and characterize physico-chemical and functional properties of polyelectrolyte microcapsules encoded with water-solubilized and stabilized with three-functional polyethylene glycol derivatives core/shell QDs. Developed microcapsules were characterized by dynamic light scattering, electrophoretic mobility, scanning electronic microscopy, and fluorescence and confocal microscopy approaches, providing exact data on their size distribution, surface charge, morphological, and optical characteristics. The fluorescence lifetimes of the QD-encoded microcapsules were also measured, and their dependence on time after preparation of the microcapsules was evaluated. The optimal content of QDs used for encoding procedure providing the optimal fluorescence properties of the encoded microcapsules was determined. Finally, the intracellular microcapsule uptake by murine macrophages was demonstrated, thus confirming the possibility of efficient use of developed system for live cell imaging and visualization of microcapsule transportation and delivery within the living cells

Conjugates of Ultrasmall Quantum Dots and Acridine Derivatives as Prospective Nanoprobes for Intracellular Investigations

International audienceDesigning nanoprobes in which quantum dots (QDs) are used as photoluminescent labels is an especially promising line of research due to their possible medical applications ranging from disease diagnosis to drug delivery. In spite of the significant progress made in designing such nanoprobes, the properties of their individual components, i.e., photoluminescent QDs, vectorization moieties, and pharmacological agents, still require further optimization to enhance the efficiency of diagnostic or therapeutic procedures. Here, we have developed a method of engineering compact multifunctional nanoprobes based on functional components with optimized properties: bright photoluminescence of CdSe/ZnS (core/shell) QDs, a compact and effective antitumor agent (an acridine derivative), and direct conjugation of the components via electrostatic interaction, which provides a final hydrodynamic diameter of nanoprobes smaller than 15 nm. Due to the possibility of conjugating various biomolecules with hydroxyl and carboxyl moieties to QDs, the method represents a versatile approach to the biomarker-recognizing molecule imaging of the delivery of the active substance as part of compact nanoprobes