Étude de l'activité physique de suppression tumorale de la protéine KBP2 dans les lignées de cellules de carcinome du sein MCF7

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Suppression of nonlinear distortion in few-mode fibres using strong mode coupling

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.

The relationship between fusion, suppression, and diplopia in amblyopia

Purpose: Traditionally, it has been thought that no binocular combination occurs in amblyopia. However, there is a growing body of evidence that there are intact binocular mechanisms in amblyopia rendered inactive under normal viewing conditions due to imbalanced monocular inputs. Georgeson and Wallis (2014) recently introduced a novel method to investigate fusion, suppression and diplopia in normal population. We have modified this method to assess binocular interactions in amblyopia. Methods: Ten amblyopic and ten control subjects viewed briefly-presented (200 ms) pairs of dichoptically separated horizontal Gaussian blurred edges. Subjects reported one central edge, one offset edge, or a double edge as the vertical disparity was manipulated. The experiment was conducted at a range of spatial scales (blur widths of 4, 8, 16, and 32 arc min) and contrasts. Our model, based Georgeson and Wallis (2014), converted subjects’ responses into probabilities of fusion, suppression, and diplopia. Results: When the normal participants were presented equal contrast to each eye the probability of fusion gradually decreased with increasing disparity, as the probability of diplopia gradually increased. In only a small proportion of the trials, normal participants experienced suppression. The pattern was consistent across all edge blurs. Interestingly, the majority of amblyopes had a comparable pattern of fusion, i.e. decreasing probability with increasing disparity. However, with increasing disparity the amblyopes tended to suppress the amblyopic eye, experiencing diplopia only in a small proportion of trials particularly at large blurs. Increasing the interocular contrast offset favouring the amblyopic eye normalized the pattern of data in a way similar to normal participants. There were some interesting exceptions: strong suppressors for which our contrast range was inadequate and one case in which diplopia dominated. Conclusions: This task is suitable for assessing binocular interactions in amblyopic participants and providing a way to quantify the relationship between fusion, suppression and diplopia. In agreement with previous studies, our data indicate the presence of binocular mechanisms in amblyopia. A contrast offset favouring the amblyopic eye normalizes the measured binocular interactions in the amblyopic visual system.

Suppression of patterning effects in digital communications by an adaptive constrained coding

We quantify the error statistics and patterning effects in a 5x 40 Gbit/s WDM RZ-DBPSK SMF/DCF fibre link using hybrid Raman/EDFA amplification. We propose an adaptive constrained coding for the suppression of errors due to patterning effects. It is established, that this coding technique can greatly reduce the bit error rate (BER) value even for large BER (BER > 101). The proposed approach can be used in the combination with the forward error correction schemes (FEC) to correct the errors even when real channel BER is outside the FEC workspace.

Self-cutting and prospective repetition of self-harm: studies of emergency department presentations in Ireland

Background Self-harm places an individual at increased risk of future self-harm and suicide, and indicates distress and maladaptive coping. Those who present to hospital with self-cutting form a significant minority of self-harm patients who are at increased risk of prospective repetition of self-harm and suicide compared with those presenting with intentional overdose. In addition to increased risk, there is emerging evidence of demographic, psychological, clinical, and social differences between those presenting with self-cutting and those presenting with overdose. Aim and Key Objectives The aim of the current doctoral work was to examine in detail the association between presenting with self-cutting and risk of prospective repetition. The objectives were: to identify evidence-based risk factors for repetition of self-harm among those presenting to emergency departments with self-harm; to compare demographic and presentation characteristics and prospective repetition across presentations of self-cutting only, self-cutting plus intentional overdose, and intentional overdose only; to compare prospective repetition and other characteristics within self-cutting presentations based on the type of treatment received; to compare self-cutting and intentional overdose patients on psychological risk and protective factors for repetition; and to examine the lived experience of engaging in repeated overdose and self-cutting. Methods The current doctoral work used a mixed-methods approach and is comprised of one systematic review and four empirical studies. The empirical studies were two registry-based prospective studies of Irish hospital presentations of self-harm, one prospective structured interview study, and one qualitative study using Interpretative Phenomenological Analysis. Results The systematic review identified several consistent and emerging risk factors for repetition of self-harm, compared to which self-cutting had a medium-sized effect. The registry studies demonstrated that the involvement of self-cutting, particularly less medically severe selfcutting, confers an increased risk of 1-month and 12-month repetition among Irish index selfharm presentations. The structured psychological study detected higher hopelessness and lower non-reactivity to inner experience among those presenting with self-cutting, and higher depression among those who repeated self-harm. Repeaters had lower baseline levels of protective psychological factors than non-repeaters and continued to have higher depression and hopelessness at follow-up. Finally, the qualitative study indicated that self-harm is a purposeful action taken in response to an overwhelming situation and is evaluated afterwards in terms of personal and social effects. Chosen method of self-harm seemed to be influenced by the desired outcome of the self-harm act, capability, accessibility and previous experience. Conclusion Despite limitations in terms of recruitment rates, the work presented in this thesis is innovative in examining the issue of the association between self-cutting and repetition from multiple perspectives. No one factor can reliably predict all repetition but self-cutting represents one consistent and easily detected risk factor for repetition. Those who present with self-cutting exhibit significant differences on demographic, clinical, and psychological variables compared with those presenting with intentional overdose, and seem to exhibit a more vulnerable profile. However, those who present with self-cutting do not form a discrete or homogenous group, and self-harm methods and levels of suicidal intent are liable to fluctuate over time.

Mécanismes de suppression tumorale impliqués lors de la sénescence induite par les oncogènes

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Étude de l'activité physique de suppression tumorale de la protéine KBP2 dans les lignées de cellules de carcinome du sein MCF7

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Suppression of nuclear factor-κB activity in macrophages by chylomicron remnants: modulation by the fatty acid composition of the particles

Current evidence indicates that chylomicron remnants (CMR) induce macrophage foam cell formation, an early event in atherosclerosis. Inflammation also plays a part in atherogenesis and the transcription factor nuclear factor-kappaB (NF-kappaB) has been implicated. In this study, the influence of CMR on the activity of NF-kappaB in macrophages and its modulation by the fatty acid composition of the particles were investigated using macrophages derived from the human monocyte cell line THP-1 and CMR-like particles (CRLPs). Incubation of THP-1 macrophages with CRLPs caused decreased NF-kappaB activation and downregulated the expression of phospho-p65-NF-kappaB and phospho-IkappaBalpha (pIkappaBalpha). Secretion of the inflammatory cytokines tumour necrosis factor alpha, interleukin-6 and monocyte chemoattractant protein-1, which are under NF-kappaB transcriptional control, was inhibited and mRNA expression for cyclooxygenase-2, an NF-kappaB target gene, was reduced. CRLPs enriched in polyunsaturated fatty acids compared with saturated or monounsaturated fatty acids had a markedly greater inhibitory effect on NF-kappaB binding to DNA and the expression of phospho-p65-NF-kappaB and pIkappaB. Lipid loading of macrophages with CRLPs enriched in polyunsaturated fatty acids compared with monounsaturated fatty acids or saturated fatty acids also increased the subsequent rate of cholesterol efflux, an effect which may be linked to the inhibition of NF-kappaB activity. These findings demonstrate that CMR suppress NF-kappaB activity in macrophages, and that this effect is modulated by their fatty acid composition. This downregulation of inflammatory processes in macrophages may represent a protective effect of CMR which is enhanced by dietary polyunsaturated fatty acids.

Quantification of glycine betaine, choline and trimethylamine N-oxide in seawater particulates: Minimisation of seawater associated ion suppression

A liquid chromatography/mass spectrometry (LC/MS, electrospray ionisation) method has been developed for the quantification of nitrogenous osmolytes (N-osmolytes) in the particulate fraction of natural water samples. Full method validation demonstrates the validity of the method for measuring glycine betaine (GBT), choline and trimethylamine N-oxide (TMAO) in particulates from seawater. Limits of detection were calculated as 3.5, 1.2 and 5.9 pg injected onto column (equivalent to 1.5, 0.6 and 3.9 nmol per litre) for GBT, choline and TMAO respectively. Precision of the method was typically 3% for both GBT and choline and 6% for TMAO. Collection of the particulate fraction of natural samples was achieved via in-line filtration. Resulting chromatography and method sensitivity was assessed and compared for the use of both glass fibre and polycarbonate filters during sample collection. Ion suppression was shown to be a significant cause of reduced instrument response to N-osmolytes and was associated with the presence of seawater in the sample matrix

Quantification of glycine betaine, choline and trimethylamine N-oxide in seawater particulates: Minimisation of seawater associated ion suppression

A liquid chromatography/mass spectrometry (LC/MS, electrospray ionisation) method has been developed for the quantification of nitrogenous osmolytes (N-osmolytes) in the particulate fraction of natural water samples. Full method validation demonstrates the validity of the method for measuring glycine betaine (GBT), choline and trimethylamine N-oxide (TMAO) in particulates from seawater. Limits of detection were calculated as 3.5, 1.2 and 5.9 pg injected onto column (equivalent to 1.5, 0.6 and 3.9 nmol per litre) for GBT, choline and TMAO respectively. Precision of the method was typically 3% for both GBT and choline and 6% for TMAO. Collection of the particulate fraction of natural samples was achieved via in-line filtration. Resulting chromatography and method sensitivity was assessed and compared for the use of both glass fibre and polycarbonate filters during sample collection. Ion suppression was shown to be a significant cause of reduced instrument response to N-osmolytes and was associated with the presence of seawater in the sample matrix

Suppression of Hydrogen Emission in a White-light Solar Flare

We present an analysis of an X-class flare that occurred on 11 June 2014 in active region NOAA 12087 using a newly developed high cadence Image
Selector operated by Astronomical Institute in Ondrejov, Czech Republic. This instrument provides spectra in the 350 - 440 nm wavelength range, which
covers the higher order Balmer lines as well as the Balmer jump at 364 nm. However, no detectable increase in these emissions were detected during
the flare, and support observations from SDO/EVE MEGS-B also show that the Lyman line series and recombination continuum were also suppressed,
particularly when compared to an M-class flare that occurred an hour earlier, and two other X-class flares on the preceding day. The X-class flare under
investigation also showed strong white light emission in SDO/HMI data, as well as an extremely hard electron spectrum ( 3.6), and
-ray emission,
from RHESSI data. This unique combination of datasets allows us to conclude that the white light emission from this flare corresponds to a black body
heated by high-energy electrons (and/or ions), as opposed to optical chromospheric emission from hydrogen.

Suppression of the Insulin Receptors in Adult Schistosoma japonicum Impacts on Parasite Growth and Development: Further Evidence of Vaccine Potential

To further investigate the importance of insulin signaling in the growth, development, sexual maturation and egg production of adult schistosomes, we have focused attention on the insulin receptors (SjIRs) of Schistosoma japonicum, which we have previously cloned and partially characterised. We now show, by Biolayer Interferometry, that human insulin can bind the L1 subdomain (insulin binding domain) of recombinant (r)SjIR1 and rSjIR2 (designated SjLD1 and SjLD2) produced using the Drosophila S2 protein expression system. We have then used RNA interference (RNAi) to knock down the expression of the SjIRs in adult S. japonicum in vitro and show that, in addition to their reduced transcription, the transcript levels of other important downstream genes within the insulin pathway, associated with glucose metabolism and schistosome fecundity, were also impacted substantially. Further, a significant decrease in glucose uptake was observed in the SjIR-knockdown worms compared with luciferase controls. In vaccine/challenge experiments, we found that rSjLD1 and rSjLD2 depressed female growth, intestinal granuloma density and faecal egg production in S. japonicum in mice presented with a low dose challenge infection. These data re-emphasize the potential of the SjIRs as veterinary transmission blocking vaccine candidates against zoonotic schistosomiasis japonica in China and the Philippines.