940 resultados para CCM-DEAD


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Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β-activated kinase-1 (TAK1) phosphorylation of NF-κB-activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB-mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment.

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This paper presents a research protocol for a randomised controlled efficacy trial of the ‘Dead Cool’ smoking prevention programme. Dead Cool is a three to four-hour programme designed to be used by teachers with Year 9 students in Northern Ireland. The main outcome of the programme is to prevent students from starting to smoke. The protocol reports a research design intended to test the efficacy of the programme in 20 post-primary school settings. Selected schools included those from secondary /grammar/integrated/single sex/coeducational, rural and urban schools from both the maintained and controlled state sector and independent sector schools. Outcome measures include self-reported behaviours, monitoring of carbon monoxide (CO) in exhaled breath and focus groups designed to assess implementation fidelity and opinions on efficacy in intervention schools and explore the ‘counterfactual’ potential treatments in control schools.

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BACKGROUND: Research on wild animal ecology is increasingly employing GPS telemetry in order to determine animal movement. However, GPS systems record position intermittently, providing no information on latent position or track tortuosity. High frequency GPS have high power requirements, which necessitates large batteries (often effectively precluding their use on small animals) or reduced deployment duration. Dead-reckoning is an alternative approach which has the potential to 'fill in the gaps' between less resolute forms of telemetry without incurring the power costs. However, although this method has been used in aquatic environments, no explicit demonstration of terrestrial dead-reckoning has been presented.

RESULTS: We perform a simple validation experiment to assess the rate of error accumulation in terrestrial dead-reckoning. In addition, examples of successful implementation of dead-reckoning are given using data from the domestic dog Canus lupus, horse Equus ferus, cow Bos taurus and wild badger Meles meles.

CONCLUSIONS: This study documents how terrestrial dead-reckoning can be undertaken, describing derivation of heading from tri-axial accelerometer and tri-axial magnetometer data, correction for hard and soft iron distortions on the magnetometer output, and presenting a novel correction procedure to marry dead-reckoned paths to ground-truthed positions. This study is the first explicit demonstration of terrestrial dead-reckoning, which provides a workable method of deriving the paths of animals on a step-by-step scale. The wider implications of this method for the understanding of animal movement ecology are discussed.

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Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

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Lorsque l’on s’intéresse au dégoût comme forme d’affect, on remarque que son application abonde au niveau des études cinématographiques et des arts visuels. Par contre, peu de chercheurs se sont intéressés à son analyse à travers les médias dont l’institutionnalisation académique est plus récente, comme la bande dessinée, la télésérie et le jeu vidéo. Ce mémoire a pour objectif d’étendre la pratique des études du dégoût comme affect sur ces médias, en s’attardant sur l’analyse de certaines composantes de la franchise transmédiatique The Walking Dead. De plus, comme ce corpus est marqué par une transmédialité qui dépasse les simples récurrences narratives, ce mémoire veut également produire un modèle d’analyse capable de déceler les structures génératives du dégoût qui tendent à migrer ou être partagées entre les médias de la franchise. Ce modèle sera conçu dans un premier temps par l’établissement d’un dialogue entre les études de l’affect appliquées au cinéma et aux arts visuels et les études sur l’intermédialité. La fonctionnalité de ce modèle sera ensuite testée à travers son application sur la bande dessinée, la télésérie et l’un des jeux vidéo de la franchise The Walking Dead.

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This paper develops some theoretical and methodological considerations for the development of a critical competence model (CCM). The model is defined as a set of skills and knowledge functionally organized allowing measurable results with positive consequences for the strategic business objectives. The theoretical approaches of classical model of competences, the contemporary model of competencies and human competencies model were revised for the proposal development. implementation of the model includes 5 steps: 1) conducting a job analysis considering which dimensions or facets are subject to revision, 2) identify people with the opposite performance (the higher performance and lower performance); 3) identify critical incidents most relevant to the job position, 4) develop behavioral expectation scales (bes) and 5) validate BES obtained for experts in the field. As a final consideration, is determined that the competence models require accurate measurement. Approaches considering excessive theoreticism may cause the issue of competence become a fashion business with low or minimal impact, affecting its validity, reliability and deployment in organizations.