935 resultados para tumour suppression
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Since the first discovery of S100 members in 1965, their expressions have been affiliated with numerous biological functions in all cells of the body. However, in the recent years, S100A4, a member of this superfamily has emerged as the central target in generating new avenue for cancer therapy as its overexpression has been correlated with cancer patients’ mortality as well as established roles as motility and metastasis promoter. As it has no catalytic activity, S100A4 has to interact with its target proteins to regulate such effects. Up to date, more than 10 S100A4 target proteins have been identified but the mechanical process regulated by S100A4 to induce motility remains vague. In this work, we demonstrated that S100A4 overexpression resulted in actin filaments disorganisation, reduction in focal adhesions, instability of filopodia as well as exhibiting polarised morphology. However, such effects were not observed in truncated versions of S100A4 possibly highlighting the importance of C terminus of S100A4 target recognition. In order to assess some of the intracellular mechanisms that may be involved in promoting migrations, different strategies were used, including active pharmaceutical agents, inhibitors and knockdown experiments. Treatment of S100A4 overexpressing cells with blebbistatin and Y-27632, non muscle myosin IIA (NMMIIA) inhibitors, as well as knockdown of NMMIIA, resulted in motility enhancement and focal adhesions reduction proposing that NMMIIA assisted S100A4 in regulating cell motility but its presence is not essential. Further work done using Cos 7 cell lines, naturally lacking NMMIIA, further demonstrated that S100A4 is capable of regulating cell motility independent of NMMIIA, possibly through poor maturation of focal adhesion. Given that all these experiments highlighted the independency of NMMIIA towards migration, a protein that has been put at the forefront of S100A4-induced motility, we aimed to gather further understanding regarding the other molecular mechanisms that may be at play for motility. Using high throughput imaging (HCI), 3 compounds were identified to be capable of inhibiting S100A4-mediated migration. Although we have yet to investigate the underlying mechanism for their effects, these compounds have been shown to target membrane proteins and the externalisation of S100 proteins, for at least one of the compounds, leading us to speculate that preventing externalisation of S100A4 could potentially regulate cell motility.
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We perform an extensive numerical analysis of Raman-Assisted Fibre Optical Parametric Amplifiers (RA-FOPA) in the context of WDM QPSK signal amplification. A detailed comparison of the conventional FOPA and RA-FOPA is reported and the important advantages offered by the Raman pumping are clarified. We assess the impact of pump power ratios, channel count, and highly nonlinear fibre (HNLF) length on crosstalk levels at different amplifier gains. We show that for a fixed 200 m HNLF length, maximum crosstalk can be reduced by up to 7 dB when amplifying 10x58Gb/s QPSK signals at 20 dB net-gain using a Raman pump of 37 dBm and parametric pump of 28.5 dBm in comparison to a standard single-pump FOPA using 33.4 dBm pump power. It is shown that a significant reduction in four-wave mixing crosstalk is also obtained by reducing the highly nonlinear fibre interaction length. The trend is shown to be generally valid for different net-gain conditions and channel grid size. Crosstalk levels are additionally shown to strongly depend on the Raman/parametric pump power ratio, with a reduction in crosstalk seen for increased Raman pump power contribution.
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Nonlinear distortion in few-mode fibers for intermediate coupling is studied for the first time. Coupling strengths beyond -20 dB/100m give suppression of nonlinear distortion below the isolated mode without mode coupling.
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We propose weakly-constrained stream and block codes with tunable pattern-dependent statistics and demonstrate that the block code capacity at large block sizes is close to the the prediction obtained from a simple Markov model published earlier. We demonstrate the feasibility of the code by presenting original encoding and decoding algorithms with a complexity log-linear in the block size and with modest table memory requirements. We also show that when such codes are used for mitigation of patterning effects in optical fibre communications, a gain of about 0.5dB is possible under realistic conditions, at the expense of small redundancy 10%). © 2006 IEEE.
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Funding/Support and role of the sponsor: None.
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Funding/Support and role of the sponsor: None.
Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction
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Peer reviewed
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We wish to acknowledge the support of the Brazilian agencies: CNPq, CAPES, and FAPESP (2015/07311-7 and 2011/19296-1).
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Peer reviewed
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Peer reviewed
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Peer reviewed
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We wish to acknowledge the support of the Brazilian agencies: CNPq, CAPES, and FAPESP (2015/07311-7 and 2011/19296-1).
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Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.
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Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.
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In this paper, we investigate the impact of linear mode coupling on the efficiency of intermodal four-wave mixing and on the group delay statistics in few-mode fibres. The investigation will include not only the weak or strong linear coupling regimes, but also the transition region between them, the intermediate coupling regime. This analysis will allow to assess the level of coupling strength require to suppress the nonlinear distortion in a few-mode fibre below the level of distortion for single-mode propagation without mode coupling.