838,974 research outputs found

    Numerical modelling of Bose-Einstein correlations

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    We propose extension of the algorithm for numerical modelling of Bose-Einstein correlations (BEC), which was presented some time ago in the literature. It is formulated on quantum statistical level for a single event and uses the fact that identical particles subjected to Bose statistics do bunch themselves, in a maximal possible way, in the same cells in phase-space. The bunching effect is in our case obtained in novel way allowing for broad applications and fast numerical calculations. First comparison with e+ee^+e^- annihilations data performed by using simple cascade hadronization model is very encouraging.Comment: LaTeX file and 5 eps file with figures, 9 pages altogethe

    Integrative multi-omics analysis identifies a prognostic miRNA signature and a targetable miR-21-3p/TSC2/ mTOR axis in metastatic pheochromocytoma/ paraganglioma

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    Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar y los autores pertenecientes a la UAMPheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that present variable outcomes. To date, no effective therapies or reliable prognostic markers are available for patients who develop metastatic PPGL (mPPGL). Our aim was to discover robust prognostic markers validated through in vitro models, and define specific therapeutic options according to tumor genomic features. Methods: We analyzed three PPGL miRNome datasets (n=443), validated candidate markers and assessed them in serum samples (n=36) to find a metastatic miRNA signature. An integrative study of miRNome, transcriptome and proteome was performed to find miRNA targets, which were further characterized in vitro. Results: A signature of six miRNAs (miR-21-3p, miR-183-5p, miR-182-5p, miR-96-5p, miR-551b-3p, and miR-202-5p) was associated with metastatic risk and time to progression. A higher expression of five of these miRNAs was also detected in PPGL patients’ liquid biopsies compared with controls. The combined expression of miR-21-3p/miR-183-5p showed the best power to predict metastasis (AUC=0.804, P=4.67·10-18), and was found associated in vitro with pro-metastatic features, such as neuroendocrine-mesenchymal transition phenotype, and increased cell migration rate. A pan-cancer multi-omic integrative study correlated miR-21-3p levels with TSC2 expression, mTOR pathway activation, and a predictive signature for mTOR inhibitor-sensitivity in PPGLs and other cancers. Likewise, we demonstrated in vitro a TSC2 repression and an enhanced rapamycin sensitivity upon miR-21-3p expression. Conclusions: Our findings support the assessment of miR-21-3p/miR-183-5p, in tumors and liquid biopsies, as biomarkers for risk stratification to improve the PPGL patients’ management. We propose miR-21-3p to select mPPGL patients who may benefit from mTOR inhibitorsThis work was supported by the Instituto de Salud Carlos III (ISCIII), Acción Estratégica en Salud, cofounded by FEDER, [grant number PI14/00240, PI17/01796 to M.R., PI15/00783 to A.C], the Paradifference Foundation [no grant number applicable to M.R.], the ANR [ANR-2011-JCJC-00701 MODEOMAPP to AP.G-R], the European Union [FP7/2007-2013 n° 259735, Horizon 2020 n° 633983 to AP.G-R], Epigénétique et Cancer [EPIG201303 METABEPIC to AP.G-R], the the Ligue Nationale contre le Cancer ["Cartes d'Identité des Tumeurs (CIT) program" to AP.G-R], the Institut National du Cancer, the Direction Générale de l’Offre de Soins [PRT-K 2014, COMETE-TACTIC, INCa-DGOS_8663 to AP.G-R], the Deutsche Forschungsgemeinschaft (DFG) [CRC/Transregio 205/1 “The Adrenal: Central Relay in Health and Disease“ to F.B, M.F and G.E], the Rafael del Pino Foundation [Becas de Excelencia Rafael del Pino 2017 to B.C], the Severo Ochoa Excellence Programme [project SEV-2011-0191 to M.C-F], La Caixa Foundation [B004235 to JM.R-R], the Spanish Ministry of Education, Culture and Sport [grant number FPU16/05527 to M.S.], the Site de Recherche Intégré sur le Cancer-SIRIC [CARPEM Project to N.B.] and the AECC Foundation [grant number AIO15152858 to C.M-C

    School, education and values: a view to education for values and the teaching of ethics in the nursing license degrees

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    Pode a Escola “ensinar” a Ética?... No projecto de investigação que estamos a desenvolver, no âmbito do nosso doutoramento, torna-se relevante tentarmos responder a esta questão. Abordamos o papel e o lugar da Ética, e mais especificamente da Bioética, e do seu ensino, no contexto da formação de novos enfermeiros; que o mesmo é dizer, que procuramos analisar e perceber a sua importância e pertinência no âmbito da formação em Enfermagem, ou seja, da formação para o Cuidar. Para Wittgenstein “a ética não pode ser ensinada. Se fosse necessária uma teoria para explicar a outra pessoa a essência da ética, esta não teria qualquer valor”. Será então que compete mesmo à Escola “ensinar” Ética? Porquê? Como e quando o pode ou deve fazer? É em torno destas questões que se desenvolve o projecto de investigação que gostaríamos de apresentar. Finalmente, acreditamos e defendemos que o ensino da Ética e da Bioética no curso de licenciatura em Enfermagem exige novas respostas didácticas e pedagógicas e deve ser encarado, sobretudo, como um desafio transdisciplinar. Nunca pode, portanto, ser “responsabilidade” exclusiva de uma única cadeira, ou do respectivo professor

    Escola ciutat escola

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    Escola universal, escola reflexiva

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    45 p., 25 f.O presente trabalho, elaborado no âmbito da disciplina de Projecto de Investigação da Pós-Graduação em Supervisão Pedagógica e Formação de Formadores da Escola Superior de Educação de Paula Frassinetti, pretendia ser o início do Projecto Educativo da nossa Instituição. Em primeiro lugar começámos por reflectir sobre a nossa escola e deparámo-nos com alguns problemas, descobrindo lacunas que se não fossem sinalizadas, dificilmente poderíamos construir um Projecto Educativo que fosse a imagem da nossa escola. Foi aqui que o nosso trabalho deixou de ser a sua construção passando a ser uma prospectiva do mesmo. Pretendemos assim, diagnosticar qual o tipo de escola que temos, reflectir e encontrar estratégias de mudança, de forma a enquadrá-la no modelo de escola reflexiva A partir daqui, começamos a questionar que tipo de escola temos e qual gostaríamos de ter. Desde logo deparámo-nos com uma escola pouco inovadora, ainda muito presa ao paradigma da escola tradicional, e com algumas pessoas que se opõem à mudança, porém a Directora mostrou vontade de mudar. Começámos por justificar que tipo de escola gostaríamos de ter, abordando o tema de escola reflexiva. Procedemos a leituras acerca de escola reflexiva, procurando arranjar estratégias de mudança aplicáveis à nossa escola. Partimos para o Diagnóstico da Situação, realizando uma entrevista à Directora da Instituição, entrevistas pessoais realizadas às educadoras das três valências e por ultimo, fizemos um Focus Group com as crianças do 4º ano do A.T.L. Reunidos os dados, traçamos um esquema do qual constam as propostas de intervenção na comunidade educativa, com vista à elaboração do nosso PROJECTO EDUCATIVO

    T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells: Function of intestinal epithelial exosomes

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    International audienceBackground and aims: Intestinal epithelial cells release antigen presenting vesicles (exosomes) bearing MHC class II/peptide complexes stimulating specific immune responses in vivo. To further characterize the role of human epithelial exosomes in antigen presentation, their capacity to load antigenic peptides, to bind immune target cells and to induce T cell activation was analyzed in vitro. Methods: The capacity of exosomes derived from the HLA-DR4 expressing, intestinal epithelial cell line T84, to load the HLA-DR4-specific peptide 3H-HSA 64-76 and to activate a HLA-DR4-restricted T cell hybridoma, was tested in the presence or absence of human monocyte-derived dendritic cells (DCs). Interaction of FITC-labeled exosomes with T cells and DCs was analyzed by flow cytometry and confocal microscopy. Results: T84-derived exosomes, enriched in CD9, CD81, CD82 and A33 antigen, were capable of binding specifically HSA 64-76 peptide on HLA-DR4 molecules and of interacting preferentially with DCs. HSA-loaded exosomes were unable to activate the T cell hybridoma directly, but induced a productive T cell activation through DCs. When HSA peptide was bound to exosomal HLA-DR4 molecules instead of in a soluble form, the threshold of peptide presentation by DCs was markedly decreased (x10-3). Conclusions: Exosomes released by intestinal epithelial cells bear exogenous peptides complexed to MHC class II molecules and interact preferentially with DCs, strongly potentiating peptide presentation to T cells. Epithelial exosomes constitute a powerful link between luminal antigens and local immune cells by mediating the transfer of tiny amounts of luminal antigenic information and facilitating immune surveillance at mucosal surfaces

    Vivre au milieu des livres

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    Que pèse la somme de nos lectures dans ce temps suspendu, et souvent déchiré, qui précède la décision ? Une bibliothèque n’enferme pas un répertoire de cas, auxquels nous pourrions tout uniment rapporter notre situation présente pour découvrir ce que nous avons à faire. Si les livres devaient nous rendre plus sages, ou mieux aptes à guider notre existence, le Dalaï Lama serait professeur de littérature. Et pourtant : si nous continuons à lire et à accumuler les volumes autour de nous, c’est bien que les livres nous aident à vivre à leur façon, que nos lectures ne restent pas sans effets sur la vie que nous menons. […]]]> fre https://serval.unil.ch/resource/serval:BIB_56947888885D.P001/REF.pdf http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_56947888885D7 info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_56947888885D7 info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/openAccess Copying allowed only for non-profit organizations https://serval.unil.ch/disclaimer application/pdf oai:serval.unil.ch:BIB_5694E7648F91 2022-10-01T01:20:16Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_5694E7648F91 The Antimalarial Drug Artesunate Attenuates Cardiac Injury in A Rodent Model of Myocardial Infarction. info:doi:10.1097/SHK.0000000000000963 info:eu-repo/semantics/altIdentifier/doi/10.1097/SHK.0000000000000963 info:eu-repo/semantics/altIdentifier/pmid/29757923 Khan, A.I. Kapoor, A. Chen, J. Martin, L. Rogazzo, M. Mercier, T. Decosterd, L. Collino, M. Thiemermann, C. info:eu-repo/semantics/article article 2018-06 Shock, vol. 49, no. 6, pp. 675-681 info:eu-repo/semantics/altIdentifier/eissn/1540-0514 urn:issn:1073-2322 <![CDATA[Ischemic heart disease remains the leading cause of morbidity and mortality in the Western world. Artesunate is the WHO-recommended drug of choice for complicated malaria (with organ failure). The administration of high doses of artesunate is safe in healthy volunteers (up to 8 mg/kg i.v.) and patients with severe malaria (2.4 mg/kg i.v.). We investigated the effects of artesunate (1 mg/kg) or its active metabolite dihydroartemisinin (DHA; 0.1 mg/kg) in a model of transient myocardial ischemia/reperfusion (I/R) and evaluated the mechanism of action of the observed cardioprotective effects of artesunate and DHA. We report here for the first time that the administration of artesunate at the onset of reperfusion attenuates the myocardial injury associated with I/R. The observed beneficial effects of artesunate are associated with activation of the PI3K/Akt/ERK 1/2 (RISK) pathway, activation of endothelial nitric oxide synthase, inhibition of glycogen synthase kinase-3β, inhibition of nuclear factor kappa B, and activation of the STAT3 (SAFE) pathway. In conclusion, as artesunate has an excellent safety profile, the above data should stimulate clinical trials in patients with acute coronary syndromes

    Compositional data supports decentralized model of production and circulation of artifacts in the pre-Columbian south-central Andes

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    ArticleThis is the author accepted manuscript. The final version is available from National Academy of Sciences via the DOI in this record.The circulation and exchange of goods and resources at various scales have long been considered central to the understanding of complex societies, and the Andes have provided a fertile ground for investigating this process. However, long-standing archaeological emphasis on typological analysis, although helpful to hypothesize the direction of contacts, has left important aspects of ancient exchange open to speculation. To improve understanding of ancient exchange practices and their potential role in structuring alliances, we examine material exchanges in northwest Argentina (part of the south-central Andes) during 400 BC to AD 1000 (part of the regional Formative Period), with a multianalytical approach (petrography, instrumental neutron activation analysis, laser ablation inductively coupled plasma mass spectrometry) to artifacts previously studied separately. We assess the standard centralized model of interaction vs. a decentralized model through the largest provenance database available to date in the region. The results show: (i) intervalley heterogeneity of clays and fabrics for ordinary wares; (ii) intervalley homogeneity of clays and fabrics for a wide range of decorated wares (e.g., painted Ciénaga); (iii) selective circulation of two distinct polychrome wares (Vaquerías and Condorhuasi); (iv) generalized access to obsidian from one major source and various minor sources; and (v) selective circulation of volcanic rock tools from a single source. These trends reflect the multiple and conflicting demands experienced by people in small-scale societies, which may be difficult to capitalize by aspiring elites. The study undermines centralized narratives of exchange for this period, offering a new platform for understanding ancient exchange based on actual material transfers, both in the Andes and beyond.We thank the former directors of Museo Etnográfico (University of Buenos Aires), M. N. Tarragó (2005–2015) and the late J. A. Pérez Gollán (1987–2005), who provided access to key samples and enthusiastic support for this project since its earliest stages. We also thank M. Berón (current Director of Museo Etnográfico, University of Buenos Aires), R. Cattáneo (Director of Museo de Antropología, University of Córdoba, 2011–2013), J. P. Carbonelli, M. E. De Feo, V. Puente, G. Míguez, and R. Spano for providing access to additional samples; A. Brechbuhler and E. Gillispie for assisting with lithic sample preparation and measurements; and C. Roush for preparing the samples for irradiation and for general laboratory management responsibilities. This research was primarily funded by Arts and Humanities Research Council Early Career Grant SX–5317 (2011–2013) and preliminary research was funded by British Academy Small Grant 51798 (2009) (both to M.L.). Fieldwork and petrography analyses have been supported by successive grants from Argentinean National Agency for Science and Technology (ANCyT) Raíces Program PICT 2007-00116 (to M.C.S.) and ANCyT PICT 2010-1048 (to M.A.K.). Funding was also provided by the National Council for Science and Technical Research PIP 112-2008 01-00256 (to M.C.S.) and PIP 11/042 (to M.A.K.). The Archaeometry Laboratory at the University of Missouri Research Reactor is supported in part by the National Science Foundation (BCS-1415403 and BCS-0922374)

    Age and habitat quality matters: isotopic variation of two sympatric species of rodents in Neotropical Forest

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    Dietary studies allow us to understand important ecological patterns such as intra- and interpopulation variation and interspecific differences regarding the use of food sources. Stable isotopes have been successfully employed to detect dietary differences between species and feeding shifts within a species, as a response to age, habitat use, and resource availability. Here we investigated the stable isotope compositions of carbon and nitrogen of young and adult specimens of Euryoryzomys russatus and Sooretamys angouya and their stomach contents, in a complex mosaic of vegetation in the Brazilian Atlantic Forest. Isotopes indicated a pronounced inter- and intraspecific plasticity in resource use for E. russatus and S. angouya. Plant sources were the prevalent feeding items for E. russatus, with low to intermediate consumption of arthropods. For S. angouya, plants were dominant in the stomach content, but arthropod arose as an important source. E. russatus showed more variation in isotopic signature between grids than S. angouya, suggesting that the former was more affected by habitat changes. These results allow us to better understand the ontogeny, diet and the behavioral responses to environmental variations of both species. Finally, our study contributes to reduce the lack of knowledge about sympatric species ecology and aggregates information for their conservation.Fil: Bovendorp, Ricardo Siqueira. Universidade Do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; Brasil. Universidade Estadual Paulista “Júlio de Mesquita Filho”; BrasilFil: Simoes Libardi, Gustavo. Universidade Do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Diversidad y Evolución Austral; ArgentinaFil: Sarmento, Mariana Montagner de Moraes. Universidade Do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; BrasilFil: Camargo, Plínio Barbosa. Universidade de Sao Paulo; BrasilFil: Reis Percequillo, Alexandre. Universidade Do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; Brasi
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