2,796 research outputs found

    Towards an effective use of language to explain light in the museum

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    This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Museum educators play a key role in explaining science in a museum. Verbal language is primarily used to communicate scientific concepts, but the way language shapes the explanations provided has not been investigated. This qualitative study focuses on the explanations about light provided by three museum educators to 8th grade students (13-14 years old), during unstructured visits to a science museum. The visits were audio-recorded and field notes taken. The museum educators’ language was analyzed at a micro-level, through the perspective of Cognitive Linguistics and Conceptual Metaphor theory. The results of this analysis coupled with a multidimensional framework for analysing explanations allowed an understanding on what is explained and how it is explained in the museum by museum educators. Findings show that explanations were descriptive and causal, structured by the use of hybrid lexicon and by conceptual metaphors, whose quality depends on the structural similarity between domains. Furthermore, the explanations based on geometric optics were qualitative and with low level of precision, complexity and abstractness

    Energy metabolism in human pluripotent stem cells and their differentiated counterparts

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    Background: Human pluripotent stem cells have the ability to generate all cell types present in the adult organism, therefore harboring great potential for the in vitro study of differentiation and for the development of cell-based therapies. Nonetheless their use may prove challenging as incomplete differentiation of these cells might lead to tumoregenicity. Interestingly, many cancer types have been reported to display metabolic modifications with features that might be similar to stem cells. Understanding the metabolic properties of human pluripotent stem cells when compared to their differentiated counterparts can thus be of crucial importance. Furthermore recent data has stressed distinct features of different human pluripotent cells lines, namely when comparing embryo-derived human embryonic stem cells (hESCs) and induced pluripotent stem cells (IPSCs) reprogrammed from somatic cells. Methodology/Principal Findings: We compared the energy metabolism of hESCs, IPSCs, and their somatic counterparts. Focusing on mitochondria, we tracked organelle localization and morphology. Furthermore we performed gene expression analysis of several pathways related to the glucose metabolism, including glycolysis, the pentose phosphate pathway and the tricarboxylic acid (TCA) cycle. In addition we determined oxygen consumption rates (OCR) using a metabolic extracellular flux analyzer, as well as total intracellular ATP levels by high performance liquid chromatography (HPLC). Finally we explored the expression of key proteins involved in the regulation of glucose metabolism. Conclusions/Findings: Our results demonstrate that, although the metabolic signature of IPSCs is not identical to that of hESCs, nonetheless they cluster with hESCs rather than with their somatic counterparts. ATP levels, lactate production and OCR revealed that human pluripotent cells rely mostly on glycolysis to meet their energy demands. Furthermore, our work points to some of the strategies which human pluripotent stem cells may use to maintain high glycolytic rates, such as high levels of hexokinase II and inactive pyruvate dehydrogenase (PDH). © 2011 Varum et al

    Pancreatite Aguda Recorrente na Gravidez

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    Introduction: During pregnancy pancreatitis is a rare and diagnosis is difficult. Cholelithiasis is the most frequent risk factor. Case report: A 26-year-old pregnant woman with abdominal pain, vomiting and low-grade fever. Hyperamylasemia and cholelithiasis was found and pancreatitis diagnosis was made. A second episode of acute pancreatitis was observed and treated with medical therapy. There was no foetal or neonatal complications. In puerperium a third pancreatitis occurred, a laparoscopic cholecystectomy was performed. Discussion: Diagnosis of acute pancreatitis in pregnancy is challenging and it may have serious maternal-fetal implications. Recurrent pattern should be taken into account when choosing the best treatment.info:eu-repo/semantics/publishedVersio

    Perinatal Stroke: 11 Cases

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    Introdução: Os acidentes vasculares cerebrais (AVC) são causa de epilepsia e perturbações do neurodesenvolvimento. Têm tido uma incidencia crescente atribuível em parte à melhoria das tecnicas de imagens cerebrais. Alguns diagnósticos são efectuados retrospectivamente após o periodo neonatal. O objectivo da presente serie de casos clínicos foi identificar factores comuns que possam facilitar o diagnóstico no período neonatal. Material e métodos: Estudo retrospectivo efectuado com base na consulta dos processos clinicos dos recém-nascidos, com diagnóstico de AVC entre um de Janeiro de 2003 e 31 de Dezembro de 2013. Resultados: Foram identificados onze casos de AVC perinatal, num total 28382 nados-vivos. Dois casos foram diagnosticados no periodo fetal e nove no periodo neonatal. As convulsões foram a manifestação clinica mais frequente (8 em 11 casos). A mediana da idade de diagnóstico foi um dia e variou entre um e nove dias. A ecografia transfontanelar mostrou alterações em sete casos. A ressonancia magnetica nuclear cranio-encefalica mostrou alterações em todos os casos. Cinco AVC foram arteriais isquemicos, quatro hemorragicos e dois tromboses dos seios venosos. Em seis casos foram identificadas possiveis causas. Foram observadas complicações e sequelas em quatro dos casos. Discussão: As convulsões foram a manifestação clinica mais frequentemente encontrada.Em recém-nascidos de termo com convulsões sem historia de asfixia intraparto o AVC perinatal deverá ser diagnóstico de exclusão, mesmo na ausencia de alterações na ecografia transfontanelar

    Cumulative Effect of Cardiovascular Risk Factors on Regulation of AMPK/SIRT1-PGC-1 alpha-SIRT3 Pathway in the Human Erectile Tissue

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    Cardiovascular disease risk factors (CVDRF), especially diabetes mellitus (DM), disrupt oxidative stress response. This condition underlies endothelial dysfunction, early manifested in men as erectile dysfunction. The current study is aimed at elucidating the impact of CVDRF in the oxidation responsive AMPK/SIRT1-PGC-1 alpha-SIRT3 pathway and related miRNAs in the human corpus cavernosum. Human penile tissue fragments from individuals submitted to programmed urological surgeries (n=27), aged 43-63 years, were clustered depending on the presence of CVDRF; the control group included samples from patients without CVDRF, and groups A and B included samples from patients with DM and additional CVDRF, totalizing = 3 CVDRF (group B). Dual-immunolabelling of SIRT3, SOD2, or GPX1 with alpha-actin in tissue sections was carried out. The assessment of expression levels of NOX1, phospho-AMPK alpha, total AMPK alpha, SIRT1, PGC-1 alpha, SIRT3, SOD2, and GPX1 was performed by western blotting and of miR-200a, miR-34a, miR-421, and miR-206 by real-time PCR. Phospho-AMPK alpha and SIRT3 expression was found significantly increased in group B relative to other groups, suggesting a marked influence of CVDRF, additional to DM, in the regulation of these enzymes. NOX1 was also increased in group B relative to controls. Only an increasing tendency was observed in the phospho-AMPK alpha/total AMPK alpha ratio, SIRT1, and PGC-1 alpha expression in groups A and B when compared with controls. Concerning antioxidant enzymes, GPX1 expression was found incremented in group A, but SOD2 expression was decreased in groups A and B, comparative with controls. Group B presented significantly diminished levels of miR-421 and miR-200a, but only a decreasing trend on miR-34 and miR-206 expression was observed. Taken together, our findings demonstrated that besides DM, additional CVDRF presented a cumulative effect in the cellular response to oxidative unbalance, contributing to AMPK/SIRT1-PGC-1 alpha-SIRT3 pathway activation. SOD2, a major mitochondrial antioxidant defence, did not follow the same variation

    Respiratory Morbidity in Late Preterm

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    User Identification Using Games

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    There is a significant shift towards a digital identity and yet the most common means of user authentication, username and password pairs, is an imperfect system. In this paper we present the notion of using videogames, specifically Tetris, to supplement traditional authentication methods and provide an additional layer of identity validation. Two experiments were undertaken that required participants to play a modified version of Tetris; the first experiment with a randomly ordered set of pieces and the second with the pieces appearing in a fixed order. The results showed that even simple games like Tetris demonstrate significant complexity in the available game states and that while some users displayed repeatable strategic behaviour, others were effectively random in their behaviours exhibiting no discernible strategy or repeatable behaviour. However, some pieces and gameboard scenarios encouraged users to exhibit behaviours that are more unique than others

    Perinatal Trombosis and Inherited Prothrombotic Disorders

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    Leveraging vectored vaccine candidates manufacturing to GMP compatible bioprocesse

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    Background Vectored vaccines are very efficient in the in vivo delivery of antigens either in the form of antigen protein and peptides or genetic material. The bioprocess of vectored vaccines poses however several challenge since the viral particles to be effective must maintain their infectivity. Lentiviral and adenoviral vectors are among the particles more used in the treatment of cancer diseases modulating the immune system. Both viral vectors are currently produced in transient upstream process. While the adenoviral vectors are produced at high titers the lentiviral vector upstream process still requires further improvement. The non-lytic nature of lentivirus enables the design of stable cell lines which may improve its yields through perfusion and longer term productions, reducing costs. The application of novel methods for the downstream processing such as continuous purification will contribute to increase the yield and lower the overall cost of the manufacturing processes. Experimental approach At the upstream process, many of the challenges lentiviral bioproducts present in its manufacturing are related to the apoptosis-leading cytotoxicity of some of the vector components. Supported on our long track experience and enabling tools developed for gammaretrovirus manufacturing, we undertook the challenge of establishing a constitutive stable lentiviral producer cell line. To address this challenge we proposed to eliminate or reduce the cytotoxicity of the lentiviral vector expression components. At the downstream process lentiviral vectors face the challenges common to retroviridae family of vectors namely short half-lives at room temperature, sensitivity to pH variations and salt concentrations, and shear stress. The purification strategy developed was designed to be based on disposable and easily scalable technologies. A final concentration achieving 108 TU mL-1 was targeted since the concentration step itself allows to reduce the burden on process and improve the transduction efficiency. To address the high doses requirements we will report an improved oncolytic adenovirus purification process for phase I and II clinical trials and present a case on the use of Polysorb 20 as a replacement for Triton X-100 during cell lysis. Product recovery, potency, purity and the effect of manufacturing holding points will be discussed. Results and discussion A lentiviral producer cell line constitutively producing titers above 106 TU.mL-1.day-1 was established. The cell line showed to be stable, consistently maintaining vector productivity over one month in the absence of antibiotics. At the bioreaction process it was possible to maintain the cells continuously producing over 10 days. At downstream we implemented scalable protocols for lentiviral and adenoviral vectors that is easy to transfer to GMP environment, combining microfiltration, anion-exchange, and ultrafiltration membranes technologies toward maximization of infectious virus recovery, allowing generation of clinical-grade viral vectors without the need for cleaning validation in a cost-effective manner. Herein we will present and discuss the challenges on the biomanufacturing of lentiviral as well as adenoviral virus, the strategies and novel technologies to be adopted in order to enable a faster development of novel vectored vaccine candidates focusing on several case studies, supported by process technology innovation
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