2 resultados para PAH
em Aston University Research Archive
Resumo:
Following Andersen's (1986, 1991) study of untutored anglophone learners of Spanish, aspectual features have been at the centre of hypotheses on the development of past verbal morphology in language acquisition. The Primacy of Aspect Hypothesis claims that the association of any verb category (Aktionsart) with any aspect (perfective or imperfective) constitutes the endpoint of acquisition. However, its predictions rely on the observation of a limited number of untutored learners at the early stages of their acquisition, and have yet to be confirmed in other settings. The aim of the present thesis is to evaluate the explanatory power of the PAH in respect of the acquisition of French past tenses, an aspect of the language which constitutes a serious stumbling block for foreign learners, even those at the highest levels of proficiency (Coppieters 1987). The present research applies the PAH to the production of 61 anglophone 'advanced learners' (as defined in Bartning 1997) in a tutored environment. In so doing, it tests concurrent explanations, including the influence of the input, the influence of chunking, and the hypothesis of cyclic development. Finally, it discusses the cotextual and contextual factors that still provoke what Anderson (1991) terms "non-native glitches" at the final stage, as predicted by the PAH. The first part of the thesis provides the theoretical background to the corpus analysis. It opens with a diachronic presentation of the French past tense system focusing on present areas of competition and developments that emphasize the complexity of the system to be acquired. The concepts of time, grammatical aspect and lexical aspect (Aktionsart) are introduced and discussed in the second chapter, and a distinctive formal representation of the French past tenses is offered in the third chapter. The second part of the thesis is devoted to a corpus analysis. The data gathering procedures and the choice of tasks (oral and written film narratives based on Modern Times, cloze tests and acceptability judgement tests) are described and justified in the research methodology chapter. The research design was shaped by previous studies and consequently allows comparison with these. The second chapter is devoted to the narratives analysis and the third to the grammatical tasks. This section closes with a summary of discoveries and a comparison with previous results. The conclusion addresses the initial research questions in the light of both theory and practice. It shows that the PAH fails to account for the complex phenomenon of past tense development in the acquisitional settings under study, as it adopts a local (the verb phrase) and linear (steady progression towards native usage) approach. It is thus suggested that past tense acquisition rather follows a pendular development as learners reformulate their learning hypotheses and become increasingly able to shift from local to global cues and so to integrate the influence of cotext and context in their tense choice.
Resumo:
Aims: Pulmonary arterial hypertension [1] is a proliferative disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMCs). Reactive oxygen species (ROS) is implicated in the development of PAH and regulates the vascular tone and functions. However, which cellular signaling mechanisms are triggered by ROS in PAH is still unknown. Hence, here we wished to characterize the signaling mechanisms triggered by ROS. Methods and Results: By Western blots, we showed that increased intracellular ROS caused inhibition of the glycolytic pyruvate kinase M2 (PKM2) activity through promoting the phosphorylation of PKM2. Monocrotaline (MCT)-induced rats developed severe PAH and right ventricular hypertrophy, with a significant increase in the P-PKM2 and decrease in pyruvate kinase activity which could be attenuated with the treatments of PKM2 activators, FBP and l-serine. The antioxidant NAC, apocynin and MnTBAP had the similar protective effects in the development of PAH. In vitro assays confirmed that inhibition of PKM2 activity could modulate the flux of glycolytic intermediates in support of cell proliferation through the increased pentose phosphate pathway (PPP). Increased ROS and decreased PKM2 activity also promoted the Cav1.2 expression and intracellular calcium. Conclusion: Our data provide new evidence that PKM2 makes a critical regulatory contribution to the PAHs for the first time. Decreased pyruvate kinase M2 activity confers additional advantages to rat PASMCs by allowing them to sustain anti-oxidant responses and thereby support cell survival in PAH. It may become a novel treatment strategy in PAH by using of PKM2 activators.