11 resultados para Promoter region

em Instituto Politécnico do Porto, Portugal


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Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c.-124 and c.-146 bp, are frequent in several human cancers; yet its presence in gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c.-124C>T mutation was the most common event, present in 2.3% (3/130), and the c.-146C>T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient's clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.

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João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.

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In the present paper we will consider strategies of innovation, risk and proactivity as entre/ intrapreneurship strategies. This study was done in a Portuguese and in a Polish region. In Portugal the region was Vale do Sousa, located in the northern Portugal. The Polish region was Lublin Voivodeship and it is situated in the south-eastern part of the country. The study focused on Industrial and Construction sectors. In order to get a valid sample, a group of 251 firms were analysed in Portugal, and 215 in Poland. However, the minimum sample size in Poland should be 323. Since this is a work in progress, we are aiming for this number of questionnaires. Each strategy was analysed individually for both regions and the results pointed to a lack of culture of entrepreneurship in firms’ management. Only Proactivity presented a positive result in firms’ management. Polish firms tend to be more innovative and more risk takers, while in proactivity Portuguese ones present a slightly higher result. Combining the strategy results, it was possible to identify that 61.2% of Portuguese firms present a low level of entrepreneurship, while 60% of Polish firms present a moderate level. Considering intrapreneurship good levels, while Portugal account for 5.2% this figure is 19.1% in Poland.

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In the present paper we analyzed the behavior of firms in the construction and manufacturing sectors, located in the region of Vale do Sousa, in the north of Portugal. From the literature, even existing some disagreements, it is possible to conclude that planning is crucial for firms survival and growth. Cooperation is another aspect that the literature presents as an important factor for firms sustainability. It also plays a major role in competition, since firms are adopting coopetition strategies. By studying a sample of 251 firms, it was possible to realize, that the majority started their business without a formal planning, and they keep going without using it. In cooperation aspects, there is a lack of cooperation. It was possible to verify, that existing cooperation has some evidence but at a vertical level. These vertical relations were also identified in stakeholder’s involvement.

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Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations. Both in thyroid cancers and glioblastoma, TERT promoter mutations are significantly associated with older age of the patients. Our results show that TERT promoter mutations are relatively frequent in specific types of human cancers, where they lead to enhanced expression of telomerase.

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Every year European citizens become victims of devastating fires, which are especially disastrous for Southern European countries. Apart from the numerous health and economic consequences, fires generate hazardous pollutants that are introduced into the environment, thus representing serious risks for public health. In that regard, particulate matter (PM) is of amajor concern. Thus, the objectives of thisworkwere to characterize the trend of forest fire occurrences and burnt area during the period of 2005 and 2010 and to study the influence of forest fires on levels of particulatematter PM10 and PM2.5. In 2010, 22,026 forest fires occurred in Portugal. The northern region was the most affected by forest fires, with 27% of occurrences in Oporto district. The annual means of PM10 and PM2.5 concentrations at two urban background sites were 25±14 μg m−3 and 8.2±4.9 μg m−3, and 17±13 μg m−3 and 7.3±5.9 μg m−3, respectively. At both sites the highest levels of PMfractionswere observed during July and August of 2010, corresponding to the periods when majority (66%) of forest fires occurred. Furthermore, PM10 daily limit at the two sites was exceeded during 20 and 5 days, respectively; 56%, and respectively 60% of those exceedances occurred during the forest fire season. Considering that the risks of forest fire ignition and severity are enhanced with elevated temperatures, the climate change might increase the environmental impacts of forest fires.

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In real-time systems, there are two distinct trends for scheduling task sets on unicore systems: non-preemptive and preemptive scheduling. Non-preemptive scheduling is obviously not subject to any preemption delay but its schedulability may be quite poor, whereas fully preemptive scheduling is subject to preemption delay, but benefits from a higher flexibility in the scheduling decisions. The time-delay involved by task preemptions is a major source of pessimism in the analysis of the task Worst-Case Execution Time (WCET) in real-time systems. Preemptive scheduling policies including non-preemptive regions are a hybrid solution between non-preemptive and fully preemptive scheduling paradigms, which enables to conjugate both world's benefits. In this paper, we exploit the connection between the progression of a task in its operations, and the knowledge of the preemption delays as a function of its progression. The pessimism in the preemption delay estimation is then reduced in comparison to state of the art methods, due to the increase in information available in the analysis.

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In embedded systems, the timing behaviour of the control mechanisms are sometimes of critical importance for the operational safety. These high criticality systems require strict compliance with the offline predicted task execution time. The execution of a task when subject to preemption may vary significantly in comparison to its non-preemptive execution. Hence, when preemptive scheduling is required to operate the workload, preemption delay estimation is of paramount importance. In this paper a preemption delay estimation method for floating non-preemptive scheduling policies is presented. This work builds on [1], extending the model and optimising it considerably. The preemption delay function is subject to a major tightness improvement, considering the WCET analysis context. Moreover more information is provided as well in the form of an extrinsic cache misses function, which enables the method to provide a solution in situations where the non-preemptive regions sizes are small. Finally experimental results from the implementation of the proposed solutions in Heptane are provided for real benchmarks which validate the significance of this work.

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Learning is not only happening in school or university; it is also an important aspect of the daily life that allows students to remain in their biological and physical environment helping to reshape it, by applying what they have learnt. Today, the higher education sector is a part of important strategies used by countries in order to foster their development. Despite its geographical location, i.e. its closeness to Europe and Asia, the MENA (Middle East and North Africa) region still needs an integrated strategy for the advancement, reform, and update of its higher educational landscape. Although some solutions have been experimented in the region in the field of higher education, they have not been able to raise the quality of education to the level comparable that observed in developed countries. In other words, many MENA higher education systems are facing problems, for which solution ought to be sought. We analyse the situation of higher education systems in the MENA countries and the factors that affect the delay in achieving the level of education existing in other world regions, e.g. Europe, especially in the higher education sector. During the discussion, the impact of new technology-enhanced tools, such as remote laboratories, in the process of development and consolidation of MENA universities, is particularly stressed.

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Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01–53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36–415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.

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Recruitment is based on a conglomerate of techniques and procedures put in place to attract qualified. The recruitment process has suffered changes, becoming even more sophisticated, involving a whole organisation and a whole community. A new source of recruitment has emerged with the use of online social networks using facilitators in its development and usage, allowing the search for candidates to be fast, cheap and "global". In Portugal, the information available and studies conducted into this phenomenon are still irrelevant, with little reported on the importance of online social recruitment. The purpose of this article is to contribute to what is understood by the professional process of recruitment through online social media by recruitment companies in the Northern Region of Portugal, analysing the use of online media by recruitment professionals, facilitator support tools and the associated best practices.