Inhibition of calcium/calmodulin kinase II alpha subunit expression results in epileptiform activity in cultured hippocampal neurons

Several models that develop epileptiform discharges and epilepsy have been associated with a decrease in the activity of calmodulin-dependent kinase II. However, none of these studies has demonstrated a causal relationship between a decrease in calcium/calmodulin kinase II activity and the development of seizure activity. The present study was conducted to determine the effect of directly reducing calcium/calmodulin-dependent kinase activity on the development of epileptiform discharges in hippocampal neurons in culture. Complimentary oligonucleotides specific for the α subunit of the calcium/calmodulin kinase were used to decrease the expression of the enzyme. Reduction in kinase expression was confirmed by Western analysis, immunocytochemistry, and exogenous substrate phosphorylation. Increased neuronal excitability and frank epileptiform discharges were observed after a significant reduction in calmodulin kinase II expression. The epileptiform activity was a synchronous event and was not caused by random neuronal firing. Furthermore, the magnitude of decreased kinase expression correlated with the increased neuronal excitability. The data suggest that decreased calmodulin kinase II activity may play a role in epileptogenesis and the long-term plasticity changes associated with the development of pathological seizure activity and epilepsy.

Learning by exporting:lesson from high-technology SMEs

Theory points to the existence of a learning by exporting effect, in which exposure to export markets enhances performance through exposure to the knowledge stocks of trading partners. We investigate the learning by exporting hypothesis by examining the effect of exporting on the subsequent innovation performance of UK high-tech SMEs. We find evidence of learning by exporting, but the pattern of this effect is relatively complex. Exporting helps high-tech SMEs innovate subsequently, but does not make them more innovation intensive. There is also evidence that it is consistent exposure to export markets that helps firms overcome the innovation hurdle, but that there is a positive scale effect of exposure to export markets which allows innovative firms to sell more of their new-to-market products on entering export markets. Service sector firms are able to reap the benefits of exposure to export markets at an earlier (entry) stage of the internationalization process than are manufacturing firms. Firms producing a rapidly changing portfolio of innovative products exhibit higher churn in terms of entry to and exit from export markets than low-intensity innovators, and this is reflected in the effects of entry and exit into and out of such markets.

The importance of social embeddedness

This article argues the importance of social embeddedness at mobile providers by examining the effects of customers’ network topological properties on churn probability—the probability of a customer switching from one telecommunication provider to another. This article uses data from regional snowball sampling—the only practically feasible network sampling method—to identify groups with significantly different churn ratios for customers with different network topological properties. Clear evidence indicates that individual network characteristics (node-level metrics) have considerable impact on churn probabilities. The inclusion of network-related measures in the churn model allows a longer-term projection of churners and improves the predictive power of the model.With no possibility to carry out repeated sampling, sample stability was checked through simulation results. On the one hand, this article highlights the importance and effectiveness of the provider’s tailored marketing campaigns by showing that customers targeted by direct marketing campaigns are less threatened by churn than nontargeted customers. On the other, this article shows that social embeddedness blocks the impact of the very samemarketing efforts. This article forwards the idea that social embeddedness, also prevalent in vendor switching, can be extended to understanding the development of professional societies threatened by membership churn.

Social contact and trust: a study of a super diverse neighbourhood

This thesis presents an in-depth case study of a superdiverse neighbourhood in Glasgow where long-term white and ethnic minority communities reside alongside Roma migrants, asylum seekers and refugees, young professionals and other recent arrivals in traditional tenement housing. It focuses on the nature and extent of social contact and trust and on the role of context in shaping social relations. Employing the concepts of social milieu and intersectionality to identify social differences the research examines the relationships between five broad groupings of residents in the neighbourhood: Nostalgic Working Class, Scottish Asian, Liberal Homeowners, Kinship-sited Roma and Global Migrants. Ethnographic fieldwork was carried out in contexts within the neighbourhood, theorised as being potential sites for intergroup contact. Three types of interactions were examined: Group-based Interactions, Neighbour Interactions and Street Interactions. The data comprised documentary evidence, participant and direct observations, in-depth qualitative and walk-along interviews with residents and local organisations. Findings show that rather than individualising and isolating residents, superdiversity can stimulate community activism, yet there remains a preference for interaction within one’s own social milieu. The research has found that the concentration of poverty and material conditions has a more profound effect on social relations than historical diversity and the extent to which diversity is normalised within local discourses. Trust judgements in a superdiverse context may rely more on shared interests, moral outlook and assessments of the context rather than the extent of social contact. The quasi-private spaces of shared residential spaces and community activities can facilitate encounters with the potential to build trust, yet for this to occur cooperation through shared activities may not be sufficient. Interactions may need to move beyond co-presence and conviviality to increased understanding and empathy through dialogue. At an aggregate level, the extent to which superdiversity contributes to social contact and trust within the neighbourhood is strongly influenced by contextual factors and wider economic processes influencing housing tenure mix, private renting, property maintenance, residential churn and environmental conditions. Through examining different types of social contacts, the dynamics of trust as well as contextual influences, this thesis offers insights into the causal processes and factors that influence social relations at a local level.