28 research outputs found

    Literacy and emancipation: on the work and thought of Myriam Nemirovsky (Alfabetizar y emancipar: sobre el trabajo y el pensamiento de Myriam Nemirovsky)

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    This article reviews contributions to teaching reading and writing of Myriam Nemirovsky, whose conceptualization foreshadowed an emancipatory pedagogy. To do so, we have reviewed her work and interviewed three of her colleagues: Elena Laiz Sasiain, Liliana Tolchinsky Brenman and Francesco Tonucci. In the first part we recount key moments in Nemirovsky’s life and set forth ideas that helped her to develop her approaches to teaching reading and writing. The text explores the development of her pedagogical thinking based on her teaching and research experiences. Later, we present parallels between Myriam Nemirovsky’s work and ideas of Jaques Rancière and Joseph Jacotot to highlight core elements in an emancipatory pedagogy and illustrate their presence in Myriam Nemirovsky’s practices and thinking. To conclude, we reflect on how Nemirovsky’s teachings helped to mobilize innovative ideas among educators. Her legacy includes a conception in which learning how to read and write is a contextualized process already underway, always unfinished, in constant transformation and largely unpredictable. It is a vision which no longer prioritizes the measurable, neutral and standardizable

    Regulation of pH by Carbonic Anhydrase 9 Mediates Survival of Pancreatic Cancer Cells With Activated KRAS in Response to Hypoxia.

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    Background & Aims Most pancreatic ductal adenocarcinomas (PDACs) express an activated form of KRAS, become hypoxic and dysplastic, and are refractory to chemo and radiation therapies. To survive in the hypoxic environment, PDAC cells upregulate enzymes and transporters involved in pH regulation, including the extracellular facing carbonic anhydrase 9 (CA9). We evaluated the effect of blocking CA9, in combination with administration of gemcitabine, in mouse models of pancreatic cancer. Methods We knocked down expression of KRAS in human (PK-8 and PK-1) PDAC cells with small hairpin RNAs. Human and mouse (KrasG12D/Pdx1-Cre/Tp53/RosaYFP) PDAC cells were incubated with inhibitors of MEK (trametinib) or extracellular signal-regulated kinase (ERK), and some cells were cultured under hypoxic conditions. We measured levels and stability of the hypoxia-inducible factor 1 subunit alpha (HIF1A), endothelial PAS domain 1 protein (EPAS1, also called HIF2A), CA9, solute carrier family 16 member 4 (SLC16A4, also called MCT4), and SLC2A1 (also called GLUT1) by immunoblot analyses. We analyzed intracellular pH (pHi) and extracellular metabolic flux. We knocked down expression of CA9 in PDAC cells, or inhibited CA9 with SLC-0111, incubated them with gemcitabine, and assessed pHi, metabolic flux, and cytotoxicity under normoxic and hypoxic conditions. Cells were also injected into either immune-compromised or immune-competent mice and growth of xenograft tumors was assessed. Tumor fragments derived from patients with PDAC were surgically ligated to the pancreas of mice and the growth of tumors was assessed. We performed tissue microarray analyses of 205 human PDAC samples to measure levels of CA9 and associated expression of genes that regulate hypoxia with outcomes of patients using the Cancer Genome Atlas database. Results Under hypoxic conditions, PDAC cells had increased levels of HIF1A and HIF2A, upregulated expression of CA9, and activated glycolysis. Knockdown of KRAS in PDAC cells, or incubation with trametinib, reduced the posttranscriptional stabilization of HIF1A and HIF2A, upregulation of CA9, pHi, and glycolysis in response to hypoxia. CA9 was expressed by 66% of PDAC samples analyzed; high expression of genes associated with metabolic adaptation to hypoxia, including CA9, correlated with significantly reduced survival times of patients. Knockdown or pharmacologic inhibition of CA9 in PDAC cells significantly reduced pHi in cells under hypoxic conditions, decreased gemcitabine-induced glycolysis, and increased their sensitivity to gemcitabine. PDAC cells with knockdown of CA9 formed smaller xenograft tumors in mice, and injection of gemcitabine inhibited tumor growth and significantly increased survival times of mice. In mice with xenograft tumors grown from human PDAC cells, oral administration of SLC-0111 and injection of gemcitabine increased intratumor acidosis and increased cell death. These tumors, and tumors grown from PDAC patient-derived tumor fragments, grew more slowly than xenograft tumors in mice given control agents, resulting in longer survival times. In KrasG12D/Pdx1-Cre/Tp53/RosaYFP genetically modified mice, oral administration of SLC-0111 and injection of gemcitabine reduced numbers of B cells in tumors. Conclusions In response to hypoxia, PDAC cells that express activated KRAS increase expression of CA9, via stabilization of HIF1A and HIF2A, to regulate pH and glycolysis. Disruption of this pathway slows growth of PDAC xenograft tumors in mice and might be developed for treatment of pancreatic cancer

    Interaction between Myelodysplasia-Related Gene Mutations and Ontogeny in Acute Myeloid Leukemia

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    Accurate classification and risk stratification are critical for clinical decision making in patients with acute myeloid leukemia (AML). In the newly proposed World Health Organization and International Consensus classifications of hematolymphoid neoplasms, the presence of myelodysplasia-related (MR) gene mutations is included as 1 of the diagnostic criteria for AML, AML-MR, based largely on the assumption that these mutations are specific for AML with an antecedent myelodysplastic syndrome. ICC also prioritizes MR gene mutations over ontogeny (as defined in the clinical history). Furthermore, European LeukemiaNet (ELN) 2022 stratifies these MR gene mutations into the adverse-risk group. By thoroughly annotating a cohort of 344 newly diagnosed patients with AML treated at the Memorial Sloan Kettering Cancer Center, we show that ontogeny assignments based on the database registry lack accuracy. MR gene mutations are frequently observed in de novo AML. Among the MR gene mutations, only EZH2 and SF3B1 were associated with an inferior outcome in the univariate analysis. In a multivariate analysis, AML ontogeny had independent prognostic values even after adjusting for age, treatment, allo-transplant and genomic classes or ELN risks. Ontogeny also helped stratify the outcome of AML with MR gene mutations. Finally, de novo AML with MR gene mutations did not show an adverse outcome. In summary, our study emphasizes the importance of accurate ontogeny designation in clinical studies, demonstrates the independent prognostic value of AML ontogeny, and questions the current classification and risk stratification of AML with MR gene mutations

    Artistas sobre outras obras

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    Alternativas. A perspetiva sobre a produção artística tem vindo a ganhar nitidez, contornos e ao mesmo tempo novas difusões, desde que em 2010 a revista Estúdio começou a sua publicação. Abre-se um campo de contactos e de autorias que se afirma como um circuito alternativo aos mecanismos hegemónicos de legitimação. Tem-se vindo a afirmar uma produção ensaística sobre artistas emergentes, oriundos das novas potências criativas. A proposta tem sido consequente e perseguida de modo sustentado; surgem novas ligações, ano após ano. Os autores dos países de língua portuguesa e espanhola tomam conhecimento alargado, não do convencionalismo eurocêntrico do grande mercado, mas das alternativas discursivas no mundo.Esta é uma alternativa, uma instância de afirmação, uma concretização para uma perspetiva inovadora e criadora, congregadora e geradora de pensamento crítico.info:eu-repo/semantics/publishedVersio

    Abstract: Emonic Environment – Implementation Report

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    This paper presents a progress report on the implementation of the Emonic Environment (EE) – a Java-based system for improvisational creation, modification, performance, and exchange of audiovisual media. The protagonist users of the EE are non-artists whose creative drive has been impeded by the prevalent interactive interfaces that are largely passive (click-response) and discourage experimentation. We take non-idiomatic improvisation as our inspiration, and seek to present the performers with an environment where the tools for media exploration are “alive”. In doing so, we hope to encourage the creativity of people otherwise afraid to experiment. This paper describes the functionality of the EE, focusing on the user interface, multi-user network capabilities, audio (performance & synchronization) and genetic algorithms used to explore a media landscape. Key-Words: improvisation, evolution, media, neural networks, multi-user, audio & video processing.

    Welcome to the FinTech Revolution - a challenge or opportunity?

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    This event officially launched our partnership between the AGSE's Master of Financial Technologies and Bendigo Bank, following the recent opening of Community Bank at Swinburne. The panel included experts Dominic Pym, Meredith Angwin, David Nemirovsky and Melissa Mack and was moderated by Master of FinTech Course Director, Dr Dimitrios Salampasis
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