Évaluation neurobiologique des souris spontanément hypertendues : Du vieillissement à la génomique comparative

Le but de cette thèse est premièrement d’évaluer l’effet du vieillissement sur les fonctions psychomotrices des souches de souris sélectionnées génétiquement en fonction de leur tension artérielle (TA); deuxièmement, de localiser les déterminants génétiques des phénotypes psychophysiologiques à partir de souches recombinantes congéniques (RCS). Ces travaux ont mené à la publication de 4 articles. Le premier article décrit l’évaluation des fonctions psychomotrices des souches avec une tension artérielle élevée (HBP), basse (LBP) et normale (NBP). La performance aux épreuves d’exploration, d’habiletés motrices et d’apprentissage spatial, a été mesurée sur deux cohortes âgées respectivement de 12 mois et de trois mois. Indépendamment de l’âge, les HBPs sont hyperactives dans l’open-field (OF), mais pas dans le test d’exploration de trous. Inversement, les LBP explorent moins d’espaces que les NBP et, à trois mois seulement, sont hypoactives dans l’OF. Par ailleurs, les HBPs et les LBP présentent des déficits précoces de coordination motrice et des fonctions visuo-motrices. Le second article concerne l’évaluation longitudinale de la coordination motrice, de l’anxiété et de l’apprentissage spatial des souches HBP, LBP et NBP, à l’âge de deux mois et de 12 mois. Le vieillissement accentue l’hyperactivité des HBPs dans l’OF. Par contre, l’hypoactivité des souris LBP est détectable seulement à l’âge de deux mois. Indépendamment de l’âge, les souris HBP et LBP montrent une perception réduite du danger dans l’épreuve d’anxiété et des dysfonctions visuo-motrices au labyrinthe aquatique. Enfin, des déficits précoces de coordination motrice se manifestent seulement chez les HBPs. Il reste à déterminer si les déficits observés sont liés à des déterminants génétiques indépendants ou secondaires aux altérations de la tension artérielle. Le troisième article présente la comparaison entre les souches consanguines A/J et C57Bl/6J (B6) aux épreuves de l’OF, de la planche à trous, du labyrinthe aquatique et du cintre (coordination motrice). Les B6 explore d’avantage l’OF et la planche à trous. Les B6 sont moins rapides sur le cintre, mais supérieurs aux A/J dans le labyrinthe aquatique, avec une plate-forme invisible ou visible. Ces résultats démontrent l’implication de déterminants génétiques. Cette thèse se termine par un quatrième article sur la localisation des déterminants génétiques de la susceptibilité au stress dans les RCS, dérivées de A/J et B6, et présentant un agencement spécifique de 12.5% du génome. La réactivité émotionnelle est évaluée dans l’OF et le plus-maze; la réponse de stress est mesurée par radio télémétrie de la température interne pendant le stress d’immobilisation (SI) sous diète régulière et riche en sel; l’excrétion des électrolytes urinaires est dosée après 24 heures de diète salée. Les loci les plus significatifs sont situés dans les régions suivantes: de l’émotionalité dans l’OF (Emo1) sur le chr. 1 (LOD=4.6) correspondant à la région homologue impliquée dans la cohorte d’hypertension familiale du Saguenay; de la dopa décarboxylase (ddc) sur le chr. 11 pour l’émergence du plus-maze (LOD=4.7); de la protéine liant l’endotoxine (lbp) sur le chr. 2 pour l’hypothermie initiale en réponse au SI (LOD=4); et de HSP90 sur le chr. 12 pour l’excrétion de Ca++ (LOD=4.6). Des banques de données sont ensuite interrogées pour recenser les polymorphismes des régions régulatrices ou codantes des gènes candidats chez les souches ancestrales A/J et B6, dont les séquences sont disponibles pour le génome entier. Des utilitaires web permettent de dévoiler les changements dans la structure secondaire de l’ARNm, l’interférence avec des microARN ou avec d’autres motifs de liaison. Plusieurs SNPs fonctionnels ont été identifiés pour le QTL du chr. 1, particulièrement dans les éléments de régulation; ceux-ci impliquant des gènes reliés avec les réponses inflammatoire/immunitaire ou avec le système cardiovasculaire. La quantification par la PCR confirme une régulation à la baisse d’atp1a2 dans le cœur et le cerveau des souches susceptibles à l’anxiété. Ces résultats confirment l’intrication des altérations de la susceptibilité au stress et de la régulation de la TA.

Role of the human chymase (CMA1) in the conversion of big-endothelin-1 to endothelin-1 (1-31)

Abstract : The chymase-dependant pathway responsible for converting Big ET-1 to ET-1 was established in vitro. It has only been recently, in 2009, that our group demonstrated that the conversion of Big ET-1 to ET-1 (1-31) can occur in vivo in mice (Simard et al., 2009), knowing that ET-1 (1-31) is converted to ET-1 via NEP in vivo (Fecteau et al., 2005). In addition, our laboratory demonstrated in 2013 that mMCP-4, the murine analogue of human chymase, produces ET-1 (1-31) from the Big ET-1 precursor (Houde et al. 2013). Thus far, in the literature, there are no specific characterizations of recombinant chymases (human or murine). In fact, the group of Murakami published in 1995 a study characterizing the CMA1 (human chymase) in a chymostatin-dependent fashion, using Angiotensin I as a substrate (Murakami et al., 1995). However, chymostatin is a non-specific inhibitor of chymase. It has been shown that chymostatin can inhibit elastase, an enzyme that can convert Angiotensin I to Angiotensin II (Becari et al., 2005). Based on these observations, the proposed hypothesis in the present study suggests that recombinant as well as extracted CMA1 from LUVA (human mast cell line), in addition to soluble fractions of human aortas, convert Big ET-1 into ET-1 (1-31 ) in a TY-51469 (a chymase-specific inhibitor) sensitive manner. In a second component, we studied the enzyme kinetics of CMA1 with regard to the Big ET-1 and Ang I substrate. The affinity of CMA1 against Big ET-1 was greater compared to Ang I (KM Big ET- 1: 12.55 μM and Ang I: 37.53 μM). However, CMA1 was more effective in cleaving Ang I compared to Big ET-1 (Kcat / KM Big ET-1: 6.57 x 10-5 μM-1.s-1 and Ang I: 1.8 x 10-4 ΜM-1.s- 1). In a third component involving in vivo experiments, the pressor effects of Big ET-1, ET-1 and Ang I were tested in conscious mMCP-4 KO mice compared to wild-type mice. The increase in mean arterial pressure after administration of Big ET-1 was greater in wild-type mice compared to mMCP- 4 KO mice. This effect was not observed after administration of ET-1 and / or Ang I.

Airwaves: 100 years of radio

Music composition using prominent broadcast speeches across the whole twentieth century in commemoration of the centenary of Marconi's first transatlantic radio transmission. The work is based on creating music from the found objects of melody derived from spoken intonation. Recordings of the speeches are accompanied throughout by live instrumental music.

Radio and affective rhythm in the everyday

This article explores the role of radio sound in establishing what I term ‘affective rhythms’ in everyday life. Through exploring the affective qualities of radio sound and its capacity for mood generation in the home, this article explores personal affective states and personal organisation. The term affective rhythm relates both to mood, and to routine. It is the combination of both that allows the possibility of thinking about sound and affect, and how they relate to, and integrate with, routine everyday life. The notion of ‘affective rhythm’ forces us to consider the idea of mood in the light of the routine nature of everyday domestic life.

Further results with localization and mapping using range from radio

In this paper, we present recent results with using range from radio for mobile robot localization. In previous work we have shown how range readings from radio tags placed in the environment can be used to localize a robot. We have extended previous work to consider robustness. Specifically, we are interested in the case where range readings are very noisy and available intermittently. Also, we consider the case where the location of the radio tags is not known at all ahead of time and must be solved for simultaneously along with the position of the moving robot. We present results from a mobile robot that is equipped with GPS for ground truth, operating over several km.

The National Aboriginal and Torres Strait Islander Women's Health Strategy on Talkin with Tiga Bayles, 98.9 AM National Indigenous Radio Service (NIRS), Wednesday 21 July 2010. (9.00 - 10.00am).

Radio Program. Talkin with Tiga Bayles, 98.9 AM National Indigenous Radio Service (NIRS), 9.00-10.00am, Wednesday 21 July 2010. (1 hour program).----- Bronwyn Fredericks discssed the National Aboriginal and Torres Strait Islander Women’s Health Strategy was launched at the Australian Women’s Health Network (AWHN) National Conference in Hobart on the 19 May 2010. Within this radio interview the background of the Strategy is discussed, funding, who did the consultations and the writing. In the interview Bronwyn Fredericks outlines the process of the Strategy’s development and its uses for the future.----- It is important to note that this Strategy does not replace other national or State and Territory documents which identify priorities and needs. The aim is to supplement existing work.

Adaptive GPS duty cycling and radio ranging for energy-efficient localization

This paper addresses the tradeoff between energy consumption and localization performance in a mobile sensor network application. The focus is on augmenting GPS location with more energy-efficient location sensors to bound position estimate uncertainty in order to prolong node lifetime. We use empirical GPS and radio contact data from a largescale animal tracking deployment to model node mobility, GPS and radio performance. These models are used to explore duty cycling strategies for maintaining position uncertainty within specified bounds. We then explore the benefits of using short-range radio contact logging alongside GPS as an energy-inexpensive means of lowering uncertainty while the GPS is off, and we propose a versatile contact logging strategy that relies on RSSI ranging and GPS lock back-offs for reducing the node energy consumption relative to GPS duty cycling. Results show that our strategy can cut the node energy consumption by half while meeting application specific positioning criteria.

Community participation in the development of digital radio : the Australian experience

The participation of the community broadcasting sector in the development of digital radio provides a potentially valuable opportunity for non-market, end user-driven experimentation in the development of these new services in Australia. However this development path is constrained by various factors, some of which are specific to the community broadcasting sector and others that are generic to the broader media and communications policy, industrial and technological context. This paper filters recent developments in digital radio policy and implementation through the perspectives of community radio stakeholders, obtained through interviews, to describe and analyse these constraints. The early stage of digital community radio presented here is intended as a baseline for tracking the development of the sector as digital radio broadcasting develops. We also draw upon insights from scholarly debates about citizens media and participatory culture to identify and discuss two sets of opportunities for social benefit that are enabled by the inclusion of community radio in digital radio service development. The first arises from community broadcasting’s involvement in the propagation of the multi-literacies that drive new digital economies, not only through formal and informal multi- and trans-media training, but also in the ‘co-creative’ forms of collaborative and participatory media production that are fostered in the sector. The second arises from the fact that community radio is uniquely placed — indeed charged with the responsibility — to facilitate social participation in the design and operation of media institutions themselves, not just their service outputs.

Spectrum sensing, detection and optimisation in cognitive radio for non-stationary primary user signals

Cognitive radio is an emerging technology proposing the concept of dynamic spec- trum access as a solution to the looming problem of spectrum scarcity caused by the growth in wireless communication systems. Under the proposed concept, non- licensed, secondary users (SU) can access spectrum owned by licensed, primary users (PU) so long as interference to PU are kept minimal. Spectrum sensing is a crucial task in cognitive radio whereby the SU senses the spectrum to detect the presence or absence of any PU signal. Conventional spectrum sensing assumes the PU signal as ‘stationary’ and remains in the same activity state during the sensing cycle, while an emerging trend models PU as ‘non-stationary’ and undergoes state changes. Existing studies have focused on non-stationary PU during the transmission period, however very little research considered the impact on spectrum sensing when the PU is non-stationary during the sensing period. The concept of PU duty cycle is developed as a tool to analyse the performance of spectrum sensing detectors when detecting non-stationary PU signals. New detectors are also proposed to optimise detection with respect to duty cycle ex- hibited by the PU. This research consists of two major investigations. The first stage investigates the impact of duty cycle on the performance of existing detec- tors and the extent of the problem in existing studies. The second stage develops new detection models and frameworks to ensure the integrity of spectrum sensing when detecting non-stationary PU signals. The first investigation demonstrates that conventional signal model formulated for stationary PU does not accurately reflect the behaviour of a non-stationary PU. Therefore the performance calculated and assumed to be achievable by the conventional detector does not reflect actual performance achieved. Through analysing the statistical properties of duty cycle, performance degradation is proved to be a problem that cannot be easily neglected in existing sensing studies when PU is modelled as non-stationary. The second investigation presents detectors that are aware of the duty cycle ex- hibited by a non-stationary PU. A two stage detection model is proposed to improve the detection performance and robustness to changes in duty cycle. This detector is most suitable for applications that require long sensing periods. A second detector, the duty cycle based energy detector is formulated by integrat- ing the distribution of duty cycle into the test statistic of the energy detector and suitable for short sensing periods. The decision threshold is optimised with respect to the traffic model of the PU, hence the proposed detector can calculate average detection performance that reflect realistic results. A detection framework for the application of spectrum sensing optimisation is proposed to provide clear guidance on the constraints on sensing and detection model. Following this framework will ensure the signal model accurately reflects practical behaviour while the detection model implemented is also suitable for the desired detection assumption. Based on this framework, a spectrum sensing optimisation algorithm is further developed to maximise the sensing efficiency for non-stationary PU. New optimisation constraints are derived to account for any PU state changes within the sensing cycle while implementing the proposed duty cycle based detector.

Energy-efficient localization : GPS duty cycling with radio ranging

GPS is a commonly used and convenient technology for determining absolute position in outdoor environments, but its high power consumption leads to rapid battery depletion in mobile devices. An obvious solution is to duty cycle the GPS module, which prolongs the device lifetime at the cost of increased position uncertainty while the GPS is off. This article addresses the trade-off between energy consumption and localization performance in a mobile sensor network application. The focus is on augmenting GPS location with more energy-efficient location sensors to bound position estimate uncertainty while GPS is off. Empirical GPS and radio contact data from a large-scale animal tracking deployment is used to model node mobility, radio performance, and GPS. Because GPS takes a considerable, and variable, time after powering up before it delivers a good position measurement, we model the GPS behaviour through empirical measurements of two GPS modules. These models are then used to explore duty cycling strategies for maintaining position uncertainty within specified bounds. We then explore the benefits of using short-range radio contact logging alongside GPS as an energy-inexpensive means of lowering uncertainty while the GPS is off, and we propose strategies that use RSSI ranging and GPS back-offs to further reduce energy consumption. Results show that our combined strategies can cut node energy consumption by one third while still meeting application-specific positioning criteria.