1,571 research outputs found

    Behind the scenes of the matchmaking between private for-profit sector and cultural and creative sectors during pandemic. Added value, motivations, and companies’ benefits to join the Portugal #Entraemcena platform

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    The motivations and role of private agents and companies in funding culture was debated along centuries until our times (Rouzé, 2019; Santos and Conde, 1990), an historical moment where brands are increasingly associated with cultural products due to their symbolic value (Schroeder et al., 2010)and where there is an increasing appropriation of culture and creativity as a useful tool for multiple sectors businesses (Hesmondhalgh, 2013; Gehman & Soublière, 2017).info:eu-repo/semantics/publishedVersio

    Crebiz.eu: creation of a laboratory module for teaching entrepreneurship for the media and the creative industries

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    O presente artigo apresenta um enquadramento das problemáticas presentes no ensino universitário de empreendedorismo no campo das indústrias criativas e do jornalismo, e os resultados preliminares de uma análise qualitativa e quantitativa acerca dos modelos atualmente em vigor a nível global. Acrescenta-se como caso de estudo empírico as primeiras aplicações práticas do projeto Crebiz.eu, nomeadamente o projeto-piloto de ensino implementado em Portugal, a sua avaliação e as reflexões conclusivas sobre as práticas implementadas e as aprendizagens realizadas, na ótica da continuação do projeto e da criação de um Modulo de Estudo, implementável ao nível universitário europeu, focado numa modalidade de ensino-aprendizagem laboratorial do empreendedorismo para o jornalismo e as indústrias criativas.info:eu-repo/semantics/publishedVersio

    Como o jornalismo lida com a inovação: um estudo de caso das melhores práticas em Portugal

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    Os meios de comunicação social estão a viver mudanças internas em consequência das pressões económicas causadas pela quebra de receitas publicitárias e/ou de audiências. Além das óbvias contenções de custos, que permitem adiar problemas mais profundos, há um esforço de reformulação interna das redações e dos próprios produtos jornalísticos. Entender como os meios de comunicação em Portugal estão a enfrentar a mudança, em especial como estão a aplicar estratégias de inovação interna para inverter a diminuição de vendas e / ou audiências e de receitas de publicidade são objetivos do trabalho, através do qual também se pretende enquadrar a realidade nacional num quadro mais amplo. Mas pretende-se também tentar identificar que processos estão a criar / recriar que afetam a produção e disseminação de notícias, por um lado, e o fluxo de receitas, por outro, e, portanto, que diretrizes podem ser identificadas para ajudar os legacy media ou startups jornalísticas a sobreviver. Para responder às questões, utilizámos a observação-participante em três redações portuguesas e entrevistas semi-estruturadas aos seus responsáveis editoriais. As organizações foram escolhidas pela sua diversidade: uma rede de televisão que inclui um canal de sinal aberto com o noticiário mais visto do prime time e um canal de notícias 24/7; uma rádio de foco noticioso e âmbito nacional; um jornal online. Observamos que tanto a TV quanto a rádio são legacy media que, através de diferentes abordagens e ritmos, estão a remodelar os seus modelos de negócios, processos de produção de notícias e produtos editoriais. O jornal nasceu como uma operação online, não precisando de evoluir de uma lógica tradicional / analógica, mas também desenvolve estratégias de inovação. Os resultados permitem identificar o foco dos casos estudados: as estratégias internas nas redações, as estratégias empreendedoras para a evolução do modelo de negócio tradicional, e o impulsionar dos resultados financeiros.info:eu-repo/semantics/publishedVersio

    Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications.

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    BCR/ABL1-like acute lymphoblastic leukaemia (ALL) is a subgroup of B-lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements. Gene expression profiling (GEP) can identify these cases but it is expensive and not widely available. Using GEP, we identified 10 genes specifically overexpressed by BCR/ABL1-like ALL cases and used their expression values - assessed by quantitative real time-polymerase chain reaction (Q-RT-PCR) in 26 BCR/ABL1-like and 26 non-BCR/ABL1-like cases to build a statistical "BCR/ABL1-like predictor", for the identification of BCR/ABL1-like cases. By screening 142 B-lineage ALL patients with the "BCR/ABL1-like predictor", we identified 28/142 BCR/ABL1-like patients (19·7%). Overall, BCR/ABL1-like cases were enriched in JAK/STAT mutations (P < 0·001), IKZF1 deletions (P < 0·001) and rearrangements involving cytokine receptors and tyrosine kinases (P = 0·001), thus corroborating the validity of the prediction. Clinically, the BCR/ABL1-like cases identified by the BCR/ABL1-like predictor achieved a lower rate of complete remission (P = 0·014) and a worse event-free survival (P = 0·0009) compared to non-BCR/ABL1-like ALL. Consistently, primary cells from BCR/ABL1-like cases responded in vitro to ponatinib. We propose a simple tool based on Q-RT-PCR and a statistical model that is capable of easily, quickly and reliably identifying BCR/ABL1-like ALL cases at diagnosis

    DYNAMICS OF EXPANSION OF TYROSINE KINASE INHIBITOR-RESISTANT MUTANTS AS ASSESSED BY DEEP SEQUENCING OF THE BCR-ABL KINASE DOMAIN: IMPLICATIONS FOR ROUTINE MUTATION TESTING

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    Background: In Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) patients (pts), efficacy of tyrosine kinase inhibitor (TKI)-based therapies is often compromised by selection of resistant mutations in the BCR-ABL kinase domain (KD). Currently, the gold standard for BCR-ABL KD mutation screen- ing is conventional Sanger sequencing (SS). However, more sensitive approaches are desirable to allow more timely and rational therapeutic intervention. Aims: A Deep sequencing (DS) strategy based on the Roche 454 next-generation sequencing technology was set up in order to: study the dynamics of expansion of different types of BCR-ABL KD mutations in Ph+ ALL patients developing resistance to TKI-based therapies; test the ability of DS to highlight emerging clones harboring TKI-resistant mutations. Methods: 29 Ph+ ALL pts who had developed resistance to TKI-based (imatinib, dasatinib, nilotinib) therapies were selected for this retrospective analysis. All the pts were known to have developed TKI-resistant BCR-ABL mutations on treatment, as assessed by SS. To reconstruct the dynamics of mutation emergence, longitudinal re-analysis of samples from relapse backwards (n=97; 1-3 months sampling interval) was performed on a Roche GS Junior instru- ment. DS runs were designed so as to enable high sensitivity mutation calling (minimum target sequence coverage 4,000 reads). However, to minimize the likelihood of false positive results, data were analyzed filtering out all variants with &lt;1% abundance. Results: DS could successfully detect all the mutations (n=85) previously identified by SS (&gt;15% abundance). In addition, DS revealed that both those samples that had been scored as apparently wild-type by SS and those samples already known to harbor mutations as assessed by SS might be carrying one or more ‘lower level’ mutations (&lt;15% abundance). In the latter cases, clonal analysis showed complex textures with the same mutation alone and also in combination with other(s) (‘compound’ mutations) in distinct subclones. Some lower level mutations were silent or apparently irrelevant from a clinical standpoint (passenger mutations?). In more than half of the cases, however, known TKI-resistant variants could be recognized that corresponded either to ‘withdrawing’ mutants not (yet) entirely de-selected by the switch in TKI or to outgrowing mutations anticipating an imminent relapse. Lower level mutations were confirmed with independent methods (ASO-PCR, RFLP). Notably, in 16/29 (55%) pts with molecularly detectable disease but not yet evidence of cytogenetic or hematologic relapse, DS could identify emerging mutations 1 to 3 months before they became detectable by SS. In the remaining 13 pts, however, outgrowth of the TKI-resistant mutation (T315I=7, Y253H=2, E255K=2, E255V=1 and F317L=1) was so rapid that not even a strict monthly monitoring could have allowed to pick them up before they became dominant. Summary / Conclusion: Now that multiple options are available, BCR-ABL KD mutation monitoring is a precious tool to maximize the efficacy of TKI-based regimens as induction or salvage therapy of Ph+ ALL. DS proved as reliable as SS for the detection of mutations with &gt;15% abundance. As a key advantage, DS added precious quantitative and qualitative information on the full repertoire of mutated populations, that SS underestimated in more than half of the samples analyzed. TKI-resistant mutations leading to patient relapse were not necessarily preexisting at diagnosis or at the time of switchover to another TKI, underlining the importance of regular monitoring of pts. Although the majority of mutations were found to arise and take over very rapidly, a monthly monitoring by our DS approach would have allowed to identify them earlier than SS actually did - and well in advance of clinical relapse - in half of the pts. DS technologies would enable higher sensitivity mutation calling: further studies are warranted to determine the optimal lower detection limit to aim to in order to exclude both transient mutant subclones that will never take over and sequencing errors

    Estudo de Públicos de Museus Nacionais - Públicos do Museu Nacional de Machado de Castro

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    Os resultados que agora se publicam sobre os Públicos do Museu Nacional de Machado de Castro (MNMC) decorrem do Estudo de Públicos de Museus Nacionais (EPMN) promovido pela Direção-Geral do Património Cultural (DGPC), entidade responsável pelas políticas museológicas em Portugal, tendo como parceiro científico o Centro de Investigação e Estudos de Sociologia do Instituto Universitário de Lisboa (CIES-IUL) e o apoio mecenático da Fundação Millennium bcp e da ONI

    Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

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    Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

    Search for CP Violation in the Decay Z -> b (b bar) g

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    About three million hadronic decays of the Z collected by ALEPH in the years 1991-1994 are used to search for anomalous CP violation beyond the Standard Model in the decay Z -> b \bar{b} g. The study is performed by analyzing angular correlations between the two quarks and the gluon in three-jet events and by measuring the differential two-jet rate. No signal of CP violation is found. For the combinations of anomalous CP violating couplings, h^b=h^AbgVbh^VbgAb{\hat{h}}_b = {\hat{h}}_{Ab}g_{Vb}-{\hat{h}}_{Vb}g_{Ab} and hb=h^Vb2+h^Ab2h^{\ast}_b = \sqrt{\hat{h}_{Vb}^{2}+\hat{h}_{Ab}^{2}}, limits of \hat{h}_b < 0.59and and h^{\ast}_{b} < 3.02$ are given at 95\% CL.Comment: 8 pages, 1 postscript figure, uses here.sty, epsfig.st

    Search for the glueball candidates f0(1500) and fJ(1710) in gamma gamma collisions

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    Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f0(1500) and fJ(1710) via their decay to pi+pi-. No signal is observed and upper limits to the product of gamma gamma width and pi+pi- branching ratio of the f0(1500) and the fJ(1710) have been measured to be Gamma_(gamma gamma -> f0(1500)). BR(f0(1500)->pi+pi-) < 0.31 keV and Gamma_(gamma gamma -> fJ(1710)). BR(fJ(1710)->pi+pi-) < 0.55 keV at 95% confidence level.Comment: 10 pages, 3 figure
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