Studies investigating the effect of 5-HT receptors mediating a response in the neonatal intestine have been limited. There are evidences that the development of new neurones continues past postnatal term and this suggests that receptors expression may differ during maturation. Thus, 'in vitro' experiments were carried out to investigate the effects of ACh, atropine, 5-HT and its related drugs on intact intestinal segments taken from the ileum of adult and neonate rats. The application of ACh (3nM-1mM) and 5-HT (3nM-1mM) induced contractions in a concentration dependent manner in all tissues examined. The 5-HT induced contractions were only sensitive to antagonism by atropine (1μM) in segments taken from the neonates but not adults. The pre-treatment with methysergide (5-HT1/2/5-7 receptor antagonist), ritanserin (5-HT2 receptor antagonist), granisetron (5-HT3 receptor antagonist) and RS 23597 (5-HT4 receptor antagonist) at 1μM or a combination of ritanserin, granisetron, plus RS 23597 at 1μM significantly reduced or abolished contractile responses induced by 5-HT. SB 269970A (5-HT7 receptor antagonist) and WAY 100635 (5-HT1A receptor antagonist) at 1μM failed to influence contractile responses induced by 5-HT or the challenges to 5-HT receptor agonists, 5-CT (5-HT1A/7 receptor agonist) and 8-OH-DPAT (5-HT1A receptor agonist) at a concentration range of 10nM-0.1mM, indicating the unlikely involvement of 5-HT1A and 5-HT7 receptors in the mediation of contractile responses in the neonatal rat ileum. Results indicate differences in cholinergic receptor involvement during postnatal maturation and suggest the involvement of 5-HT2, 5-HT3 and 5-HT4 receptors in the mediation of contractile responses to 5-HT in the neonatal rat ileum. There is a growing need to decrease animal usage in pharmacological experiments. This may be achieved by the development of 'in vitro' cell culture models. Thus attempts were also made to develop a cell culture model of neonatal intestine to further investigate the action of pharmacologically active agents. The isolation of individual cell populations from segments taken from the intestine of rat neonates were achieved by ligation of both ends of the intestine prior to incubation in trypsin so that a gradual dissociation could be monitored. This was supported by histological procedures, determining the time required to extract large numbers of cells from different intestinal layers. Differential adhesion and selective cytotoxicity techniques were used for further purification of intestinal smooth muscle cells (ISMC), neuronal cells, and a coculture of ISMC and neuronal cells, and these were characterised through immunostaining with antibodies to α-smooth muscle actin, α-actinin and the 5-HT3 receptor. A protocol for cryopreservation of ISMC was designed in order to protect cells against genetic instability, enhance cell availability and reduce animal usage. Results showed that cells extracted from the intestine are viable for up to 4-months. ISMC functionality was analysed via the application of known pharmacologically active drugs on ISMC, which were plated onto glass and silicone elastomer substrate. The cultured ISMC responded to the application of drugs such as potassium chloride (KCl), carbachol, 5-HT and noradrenaline (NA). Large population of cocultures seeded onto silicone elastomers or cholesteric liquid crystal substrates (LC) were assessed for their ability to produce a collective response to KCl application. Attempts were made to detect any deformations of the substrate surface due to the exposure to KCl and NA. Cholesteric LC substrates seemed to be the most suitable material for investigating the cellular tensions. The availability of cell cultures allowed the development of an intestinal model of inflammation. This was achieved through the use of lipopolysaccharide (LPS)-induced inflammation and was confirmed by assessing the levels pro-inflammatory mediators interleukin (IL-8) and nitric oxide (NO), which were significantly elevated. Reduction of IL-8 ad NO was also examined using granisetron and L-NAME and Chaga mushroom extract. Granisetron and L-NAME reduced the NO production during short incubation times. However, an elevated level of NO was observed when longer treatment times were examined. The Chaga mushroom extract caused a significant reduction in NO production in the model of inflammation. This indicates that this model may be a valuable tool for the investigation of other pro-inflammatory mediators and may contribute for the investigation of more selective drugs in the management of intestinal inflammation in neonates.

Studies investigating the effect of 5-HT receptors mediating a response in the neonatal intestine have been limited. There are evidences that the development of new neurones continues past postnatal term and this suggests that receptors expression may differ during maturation. Thus, `in vitro¿ experiments were carried out to investigate the effects of ACh, atropine, 5-HT and its related drugs on intact intestinal segments taken from the ileum of adult and neonate rats. The application of ACh (3nM-1mM) and 5-HT (3nM-1mM) induced contractions in a concentration dependent manner in all tissues examined. The 5-HT induced contractions were only sensitive to antagonism by atropine (1¿M) in segments taken from the neonates but not adults. The pre-treatment with methysergide (5-HT1/2/5-7 receptor antagonist), ritanserin (5-HT2 receptor antagonist), granisetron (5-HT3 receptor antagonist) and RS 23597 (5-HT4 receptor antagonist) at 1¿M or a combination of ritanserin, granisetron, plus RS 23597 at 1¿M significantly reduced or abolished contractile responses induced by 5-HT. SB 269970A (5-HT7 receptor antagonist) and WAY 100635 (5-HT1A receptor antagonist) at 1¿M failed to influence contractile responses induced by 5-HT or the challenges to 5-HT receptor agonists, 5-CT (5-HT1A/7 receptor agonist) and 8-OH-DPAT (5-HT1A receptor agonist) at a concentration range of 10nM-0.1mM, indicating the unlikely involvement of 5-HT1A and 5-HT7 receptors in the mediation of contractile responses in the neonatal rat ileum. Results indicate differences in cholinergic receptor involvement during postnatal maturation and suggest the involvement of 5-HT2, 5-HT3 and 5-HT4 receptors in the mediation of contractile responses to 5-HT in the neonatal rat ileum. There is a growing need to decrease animal usage in pharmacological experiments. This may be achieved by the development of `in vitro¿ cell culture models. Thus attempts were also made to develop a cell culture model of neonatal intestine to further investigate the action of pharmacologically active agents. The isolation of individual cell populations from segments taken from the intestine of rat neonates were achieved by ligation of both ends of the intestine prior to incubation in trypsin so that a gradual dissociation could be monitored. This was supported by histological procedures, determining the time required to extract large numbers of cells from different intestinal layers. Differential adhesion and selective cytotoxicity techniques were used for further purification of intestinal smooth muscle cells (ISMC), neuronal cells, and a coculture of ISMC and neuronal cells, and these were characterised through immunostaining with antibodies to ¿-smooth muscle actin, ¿-actinin and the 5-HT3 receptor. A protocol for cryopreservation of ISMC was designed in order to protect cells against genetic instability, enhance cell availability and reduce animal usage. Results showed that cells extracted from the intestine are viable for up to 4-months. ISMC functionality was analysed via the application of known pharmacologically active drugs on ISMC, which were plated onto glass and silicone elastomer substrate. The cultured ISMC responded to the application of drugs such as potassium chloride (KCl), carbachol, 5-HT and noradrenaline (NA). Large population of cocultures seeded onto silicone elastomers or cholesteric liquid crystal substrates (LC) were assessed for their ability to produce a collective response to KCl application. Attempts were made to detect any deformations of the substrate surface due to the exposure to KCl and NA. Cholesteric LC substrates seemed to be the most suitable material for investigating the cellular tensions. The availability of cell cultures allowed the development of an intestinal model of inflammation. This was achieved through the use of lipopolysaccharide (LPS)-induced inflammation and was confirmed by assessing the levels pro-inflammatory mediators interleukin (IL-8) and nitric oxide (NO), which were significantly elevated. Reduction of IL-8 ad NO was also examined using granisetron and L-NAME and Chaga mushroom extract. Granisetron and L-NAME reduced the NO production during short incubation times. However, an elevated level of NO was observed when longer treatment times were examined. The Chaga mushroom extract caused a significant reduction in NO production in the model of inflammation. This indicates that this model may be a valuable tool for the investigation of other pro-inflammatory mediators and may contribute for the investigation of more selective drugs in the management of intestinal inflammation in neonates.

La modélisation de la nature (minéralogie, composition) et de la dynamique du manteau terrestre nécessite la connaissance des propriétés de ses minéraux constitutifs à haute pression (HP, 1-135 GPa) et haute température (HT, 1000-3000K). En particulier, les grandeurs thermodynamiques (enthalpies de formation, entropies, volume, ... ) contrôlent la stabilité des minéraux dans l'espace pression-température. Dans une première approche dite "macroscopique", les capacités calorifiques de la forstérite et de ses analogues, du pyrope et du spinelle sont mesurées par calorimétrie à HT. Les données de dilatation thermique et de compressibilité sont tirées de mesures de volume à HP et HT. On dispose alors d'un ensemble de données qui permet de mettre en évidence, pour la plupart de ces minéraux, un comportement anharmonique à HT. Dans une seconde approche "microscopique", les propriétés thermodynamiques d'un minéral sont calculées par modélisation vibrationnelle à partir de ses spectres infrarouge et Raman. Une méthode originale de mesure de l'anharmonicité est développée, fondée sur l'enregistrement des spectres vibrationnels à HP et HT. On montre alors pourquoi et comment les valeurs des capacités calorifiques s'écartent à HT de la limite prédite par une théorie harmonique. Cette méthode "microscopique" originale, qui ne nécessite que quelques milligrammes de matière, est ainsi développée et testée sur des matériaux pour lesquels elle peut être confrontée aux données "macroscopiques" (e.g. calorimétrie). Elle pourra dans l'avenir être appliquée aux phases de très haute pression du manteau terrestre, dont la métastabilité et les faibles quantités synthétisées empêchent la caractérisation par les méthodes classiques "macroscopiques".

By the end of the Seventeenth century, when the Dutch settlement at the Cape was already firmly established, and the foundation had thus been laid for the present political dominance of the white man in the country, Africa south of the Kunene Okavango and Zambesi Rivers was inhabited by a considerate. number of different native peoples On the basis of racial, linguistic and cultural distinction, these can all be classified into four main stocks, commonly known as the Bushmen, the Hottentots, the Bergdama and the Bantu respectively. The Bushmen are a short, brownish-yellow people, with certain peculiar and racial characteristics, they all speak languages of a uniform, well-defined and easily recognizable type, phonetically remarkable especially for the great prevalence of click consonant; and they practice neither agriculture nor pastoralism, but live in small separate commutative which lead a nomadic hunting and collecting existence.

Serving the good of the community is a professional value prized by those who work in the provincial press. It is also seen as a vital role for local newspapers by those outside the industry. A localised form of the Fourth Estate, the good of the community therefore justifies and underpins the routines and news values of those who work in regional and local news organisations. This thesis investigates the extent to which this notion serves as a functional value for the English provincial news industry; it positions it within an historical context to understand its relationship with the economic structure of the local newspaper. As such, after Foucault, it constitutes the good of the community as a discursive position which functions in different ways during different periods of development for the provincial press. The history of the provincial press is charted from its inception in the eighteenth century to the present day. This history conceptualises its development within six distinct stages; as such it seeks to demonstrate the fluidity of the notion of serving the good of the community which is presented as absolute by the industry. Interviews with current workers within the industry are used to expose the way in which the concept functions for the industry today and concomitant changes wrought by digital innovation. These demonstrate that the notion functions best at those titles which enjoy direct investment in their ability to act in a way which serves the good the community; conversely it is most under threat at those titles which are increasingly removed from their locale for reasons of profit. This thesis ends with the suggestion that preserving the ability of the provincial news industry to serve the good of the community necessitates a new approach to an assessment of its value; it suggests that alternative funding models are needed if the ability of the industry to meet this goal is to be retained.

This thesis examines the lives of a group of young working-class men in a post-industrial community in the South Wales Valleys. Using a longitudinal ethnographic approach, I focus on how young masculinities within a specific community are performed across a variety of educational and leisure spaces and indicate how social, economic and cultural processes impact on the formation of self. This thesis also describes how, within the limits of place and during different social interactions, individual young men can be seen as active agents in their own construction of identity. Ideas and issues drawn from Erving Goffman’s work on the performance of self and the formation of social identity are central to the theoretical framing of the thesis. I suggest that Goffman’s dramaturgical framework has important implications for analysing performances of masculinities. When applied to masculinities (and femininities) this framework highlights how gender comes into being through socially constructed performances which are understood (consciously and unconsciously) as socially acceptable in a given situation, setting or community, not as innate biological accomplishments but as dramaturgical tasks. Throughout the thesis, through paying attention to the diversity of social identities and relations within an ostensibly homogeneous working-class community, I challenge commonly held beliefs about working-class young men that appear in the media and in policy discourses. I argue that for a group of young men in a community of social and economic deprivation, expectations and transitions to adulthood are framed through geographically and historically shaped class and gender codes.

In the era of online business, digital devices, and electric books, bricks-and-mortar bookshops are in decline. Although the future of physical bookstores has received much anecdotal attention, little examination has occurred in the academic context. With a specific focus on the development of a comprehensive understanding of bookstore experiences, this research employs more-than-representational theory in order to conceptualise the ‘operational logics’ of bookstore experience. Through an ethnographic investigation of Eslite, one of the leading bookstore chains in Taiwan, this thesis argues that in order to thrive and sustain its bookselling business Eslite bookstores are produced as experiencescapes through performance. In these experiencescapes, consumers act as creative artisans who are able to re-configure any given situation, enacting countless possibilities through their embodied practices. Likewise, I suggest that cultural meanings, values, and ideological thoughts are connected to these embodied practices, spaces, identities and lifestyle through consumers’ book experiences. In addressing how practice constantly engages with corporate plans, cultural meanings, identities, and personal ways of life, this thesis contributes to wider debates on the processes of how the (more than) representational is presented and performed, and therefore invites researchers to develop a greater sensitivity to ‘doing’ geographies of consumption and spatial practices.

The neurotransmitters serotonin (5-HT) and dopamine (DA) play roles in eating disorders, mood disorders, such as depression and anxiety, and in the regulation of locomotion. The 5-HT2C receptor is one of fourteen 5-HT receptor subtypes that is expressed in regions of the brain including the hippocampus, amygdala, dorsal striatum, nucleus accumbens (NA) and substantia nigra, and is therefore implicated in behaviours and disorders associated with these regions. 5-HT has been shown to exert both a tonic and phasic inhibitory control, through the 5-HT2C receptor, on the firing rate and bursting activity of DA-containing neurones in the ventral tegmental area which enhances DA release in the NA and prefrontal cortex. In addition, the 5-HT2C receptor is under the control of a monophasic diurnal rhythm and is in a position to alter circadian regulation and behaviour due to its expression in the suprachiasmatic nucleus (the light entrainable oscillator (LEO)). It was hypothesised that elevating expression of the 5-HT2C receptor would have a detrimental effect on mood and cause hypolocomotion while reducing 5-HT2C receptor expression would improve mood, cause hyperphagia, obesity and hyperlocomotion. In order to investigate these hypotheses mouse models that either over- or under-expressed the 5-HT2C receptor were implemented. The 5-HT2C receptor expression pattern and levels were confirmed in all mouse lines. A behavioural phenotype of hypolocomotion and increased anxiety in the 5-HT2C receptor over-expressing mice and hyperphagia, obesity and hyperlocomotion in the 5-HT2C receptor under-expressing mice were found the latter is conistent with current literature. During backcrossing of the mouse lines onto the C57Bl/6 genetic background the abnormal behavioural phenotypes were lost suggesting that 5-HT2C receptor function is particulary sensitive to the genetic background on which it is being expressed. In response to altered expression levels of 5-HT2C receptor, compensatory alterations were found in the 5-HT system, with an inverse relationship existing between both the 5-HT1A receptor mRNA expression levels and 5-HT release in the hippocampus with the expression levels of the 5-HT2C receptor. Over-expression of 5-HT2C receptor appears to inhibit DA release in the cortex. The circadian experiments showed that under-expressing the 5-HT2C receptor did not alter the regulation of the food entrainable oscillator and there was a suggestion that the regulation of the LEO was affected. In summary, these results demonstrate that altered expression of 5-HT2C receptors results in abnormal behaviours consistent with its role in psychiatric disorders, but that the outcome is dependent on the genetic background.

No description available.

The joyous advent of democracy in South Africa in 1994 brought real promise of an improvement in the life chances for millions of marginalised South Africans. There was reason for many citizens to have great faith in the new order after decades of sustained struggle. Effective state intervention and the spatial reorganisation of society seemed a realistic prospect in a country blessed with abundant natural resources and an established industrial base. The power of the state to affect change at the grassroots level was however soon compromised by the substitution of the populist Reconstruction and Development Programme with the neoliberal Growth, Employment and Redistribution Strategy (GEAR) by mid 1996. South Africa was now part of the international community and the new government's gaze was directed away from its popular support base. The radical and risky policy shift was influenced by demands of an international investor community and by the dictates of international donor organisations. Announcement of the policy shift was a low profile affair and few citizens had any real comprehension of the impact the shift would have on the capacity of the new ANC government to deliver on its electoral promises. Change in the macro economic policy reverberated within the lower tiers of government and in local authorities. Urban development policy was repeatedly rewritten; first in response to the dictates of the socialist RDP in 1994, and again in response to a neo-liberal GEAR in 1996. In 2000 the fragmented urban management system of appointed officials was replaced by an elected metropolitan government system. This initiated a third, profound shift in the policy context as each metropolitan government sought to formulate its own, context-specific policies. The most recent shift is significant since it has resulted in massive organisational upheaval and restructuring. However, it has opened new laboratories, which generates new opportunities for more responsive and accountable policy-making and planning. These new opportunities emerge against a backdrop in which the comedy of policy shifts that have occurred during the past nine years have resulted in little action and a growing crisis on the ground. Despite the policy shifts, corridor development has remained a constant feature of post apartheid urban development frameworks. Initially it made sense as a mechanism to physically integrate fragmented cities. It fitted a populist agenda, had political currency and was an easy sell. After the adoption of neo-liberal strategies it would receive another label; that of an accessible armature for private investment. Importantly, the latest policy shift in 2000 offered an opportunity to consider the city in a holistic and integrated fashion. This represents the belated death of the Apartheid City, which was characterised by fragmented, sub-regional councils linked to racially defined urban enclaves. New metropolitan governments arguably have greater capacity to facilitate and co-ordinate action in the extended corridor zone than has ever been possible. Effective implementation of a regional capital web of minimal public investment now becomes a distinct possibility. The recent adoption of a metropolitan government system and the associated strategic urban management approach offers an opportunity for reflection and for the construction of an informed vision of the role of urban design in corridor development. Whilst the corridor concept has survived, its purpose has become confused. While not discarding the corridor idea, many proposals that originated during the early post apartheid years are being questioned by new metropolitan governments. The new crisis is largely the result of the private sector having shown reluctance to invest in marginal zones of the city. Since corridors were originally conceived as devices which aim to link marginal zones to the core of opportunity, their capacity to facilitate change is limited by the sustained lack of market interest. While the market remains reluctant to invest in the areas of greatest need in corridors, requirements for improved mobility and access amongst the urban poor have escalated dramatically as millions of migrants from the rural hinterland and the African sub-continent flock to the urban peripheries. Migrants squat on the verges of highways or crowd into the backyards of apartheid-era townships. They are effectively constructing their own informal corridors along lines of access. This dynamic adds to the emerging crisis associated with an uninterested private sector. This thesis responds to the crisis from an urban design perspective. It evaluates the actions of urban designers in the corridor context during the past decade, and tests the perceptions of ordinary citizens who are affected by corridor development. While doing this it questions the predominance of generic approaches to corridor development and draws on insights gained from international fieldwork in Malaysia, Australia and Peru. Finally, it presents a strategic approach that indicates ways in which urban design may realise its potential to become an enabling discipline in the participatory development of the post apartheid integration corridor.