Roles of transmembrane domain 2 and the first intracellular loop in human noradrenaline transporter function: pharmacological and SCAM analysis

The aim was to investigate the roles of transmembrane domain 2 and the adjacent region of the first intracellular loop in determining human noradrenaline transporter (hNET) function by pharmacological and substituted-cysteine accessibility method (SCAM) analyses. It was first necessary to establish a suitable background NET for SCAM. Alanine mutants of endogenous hNET cysteines, hC86A, hC131A and hC339A, were examined and showed no marked effects on expression or function. hNET and the mutants were also resistant to methanethiosulfonate (MTS), ethylammonium (MTSEA) and MTStrimethylammonium (MTSET). Hence, wild-type hNET is an appropriate background for production of cysteine mutants for SCAM. Pharmacological investigation showed that all mutants except hT99C and hL109C showed reduced cell-surface expression, while all except hM107C showed a reduction in functional activity. The mutations did not markedly affect the apparent affinities of substrates, but apparent affinities of cocaine were decreased 7-fold for hP97C and 10-fold for hF101C and increased 12-fold for hY98C. [H-3]Nisoxetine binding affinities were decreased 13-fold for hP97C and 5-fold for hF101C. SCAM analysis revealed that only hL102C was sensitive to 1.25 mM MTSEA, and this sensitivity was protected by noradrenaline, nisoxetine and cocaine. The results suggest that this region of hNET is important for interactions with antidepressants and cocaine, but it is probably not involved in substrate translocation mechanisms.

Combining the power of online crowdsourcing with creative writing user interfaces

The goal of this work was to provide professional and amateur writers with a new way of enhancing their productivity and mental well-being, by helping them overcoming writers block and being able to achieve a state of optimal experience while writing. Our approach is based on bringing together different components to create what we call a creative moment. A creative moment is composed by an image, a text, a mood, a location and a color. The color presented in the creative moment varied according to the mood that was associated to the creative moment. With the creative moments we hoped that our users could have a way to easily trigger their creativity and have a kick start in their work. The prototyping of a web crowdsourcing platform, named CreativeWall, and a Microsoft Word Add-In, that was used on the user study performed, is described and their implementations are discussed. The user study reveals that our approach does have a positive influence in the productivity of the participants when compared with another existing approach. The study also revealed that our approach can ease the process of achieving a state of optimal experience by enhancing one of the dimensions presented on the Flow Theory. At the end we present what we consider would be some possible future developments for the concept created during the development of this work.

Experts:the knowledge and power of expertise

In this book, Stehr and Grundmann outline the theoretical significance and practical importance of the growing stratum of experts, counsellors and advisors in contemporary society, and claim that the growing spectrum of knowledge-based occupations has led to the pluralisation of expertise. As decision makers in organizations and private citizens, for various reasons, increasingly seek advice from experts, the authors examine the nature of expert activity, and suggest that the role of experts needs to be distinguised from other roles such as professionals, scientists, or intellectuals. Experts, they argue, perform knowledge based activities that mediate between the context of knowledge creation and application. Existing approaches tend to restrict the role of the expert to scientists, or to conflate the roles of professionals with experts. In avoiding such restrictions, this book sets out a framework to understanding the growing role of expertise in a better way. Experts provides thought-provoking discussion that will be of interest to postgraduate students and academics working within the fields of social theory, knowledge, and consumption.