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The kinetics of ER fusion protein activation in vivo.
Reversibly switchable proteins are powerful tools with which to explore protein function in vitro and in vivo. For example, the activity of many proteins fused to the hormone-binding domain of the modified oestrogen receptor (ER(TAM)) can be regulated by provision or removal of 4-hydroxytamoxifen (4-OHT). Despite the widespread use of ER(TAM) fusions in vivo, inadequate data are available as to the most efficacious routes for systemic tamoxifen delivery. In this study, we have used two well-characterized ER(TAM) fusion proteins, both reversibly activated by 4-OHT, to compare the effectiveness and kinetics of 4-OHT delivery in mice in vivo by either tamoxifen in food or by intraperitoneal injection. Our data indicate that dietary tamoxifen offers an effective, facile and ethically preferable means for long-term activation of ER(TAM) fusion proteins in vivo.This is the final published version. It's also available from the publishers at: http://www.nature.com/onc/journal/vaop/ncurrent/full/onc201478a.html
When politicians and the experts collide: Organization and the creation of information spheres
This paper explores collaborative information behavior in the context of highly politicized decision making. It draws upon a qualitative case study of project management of a contentious public sector infrastructure project. We noted the creation of spaces for the development and exchange of information by experts and conceptualize these as information spheres. We postulate that these were formed to bypass power-induced information behavior that excludes expert power, such as information avoidance. This approach contrasts with the expected project management and information norms, rules and behavior, however, provides a language that can be used to explain the phenomena of bounded information spaces which complement and may be used as a development of adjunct to small world's theory
Personalisation and recommender systems in digital libraries
Widespread use of the Internet has resulted in digital libraries that are increasingly used by diverse communities of users for diverse purposes and in which sharing and collaboration have become important social elements. As such libraries become commonplace, as their contents and services become more varied, and as their patrons become more experienced with computer technology, users will expect more sophisticated services from these libraries. A simple search function, normally an integral part of any digital library, increasingly leads to user frustration as user needs become more complex and as the volume of managed information increases. Proactive digital libraries, where the library evolves from being passive and untailored, are seen as offering great potential for addressing and overcoming these issues and include techniques such as personalisation and recommender systems. In this paper, following on from the DELOS/NSF Working Group on Personalisation and Recommender Systems for Digital Libraries, which met and reported during 2003, we present some background material on the scope of personalisation and recommender systems in digital libraries. We then outline the working group’s vision for the evolution of digital libraries and the role that personalisation and recommender systems will play, and we present a series of research challenges and specific recommendations and research priorities for the field
In Defence of Modest Doxasticism About Delusions
Here I reply to the main points raised by the commentators on the arguments put forward in my Delusions and Other Irrational Beliefs (OUP, 2009). My response is aimed at defending a modest doxastic account of clinical delusions, and is articulated in three sections. First, I consider the view that delusions are in-between perceptual and doxastic states, defended by Jacob Hohwy and Vivek Rajan, and the view that delusions are failed attempts at believing or not-quite-beliefs, proposed by Eric Schwitzgebel and Maura Tumulty. Then, I address the relationship between the doxastic account of delusions and the role, nature, and prospects of folk psychology, which is discussed by Dominic Murphy, Keith Frankish, and Maura Tumulty in their contributions. In the final remarks, I turn to the continuity thesis and suggest that, although there are important differences between clinical delusions and non-pathological beliefs, these differences cannot be characterised satisfactorily in epistemic terms. \u
Effects of study design and allocation on participant behaviour-ESDA: study protocol for a randomized controlled trial
Background: What study participants think about the nature of a study has been hypothesised to affect subsequent behaviour and to potentially bias study findings. In this trial we examine the impact of awareness of study design and allocation on participant drinking behaviour.
Methods/Design: A three-arm parallel group randomised controlled trial design will be used. All recruitment, screening, randomisation, and follow-up will be conducted on-line among university students. Participants who indicate a hazardous level of alcohol consumption will be randomly assigned to one of three groups. Group A will be informed their drinking will be assessed at baseline and again in one month (as in a cohort study design). Group B will be told the study is an intervention trial and they are in the control group. Group C will be told the study is an intervention trial and they are in the intervention group. All will receive exactly the same brief educational material to read. After one month, alcohol intake for the past 4 weeks will be assessed.
Discussion: The experimental manipulations address subtle and previously unexplored ways in which participant behaviour may be unwittingly influenced by standard practice in trials. Given the necessity of relying on self-reported outcome, it will not be possible to distinguish true behaviour change from reporting artefact. This does not matter in the present study, as any effects of awareness of study design or allocation involve bias that is not well understood. There has been little research on awareness effects, and our outcomes will provide an indication of the possible value of further studies of this type and inform hypothesis generation
Sequence learning modulates neural responses and oscillatory coupling in human and monkey auditory cortex
Learning complex ordering relationships between sensory events in a sequence is fundamental for animal perception and human communication. While it is known that rhythmic sensory events can entrain brain oscillations at different frequencies, how learning and prior experience with sequencing relationships affect neocortical oscillations and neuronal responses is poorly understood. We used an implicit sequence learning paradigm (an “artificial grammar”) in which humans and monkeys were exposed to sequences of nonsense words with regularities in the ordering relationships between the words. We then recorded neural responses directly from the auditory cortex in both species in response to novel legal sequences or ones violating specific ordering relationships. Neural oscillations in both monkeys and humans in response to the nonsense word sequences show strikingly similar hierarchically nested low-frequency phase and high-gamma amplitude coupling, establishing this form of oscillatory coupling—previously associated with speech processing in the human auditory cortex—as an evolutionarily conserved biological process. Moreover, learned ordering relationships modulate the observed form of neural oscillatory coupling in both species, with temporally distinct neural oscillatory effects that appear to coordinate neuronal responses in the monkeys. This study identifies the conserved auditory cortical neural signatures involved in monitoring learned sequencing operations, evident as modulations of transient coupling and neuronal responses to temporally structured sensory input
Ant-like task allocation and recruitment in cooperative robots
One of the greatest challenges in robotics is to create machines that are able to interact with unpredictable environments in real time. A possible solution may be to use swarms of robots behaving in a self-organized manner, similar to workers in an ant colony. Efficient mechanisms of division of labour, in particular series-parallel operation and transfer of information among group members, are key components of the tremendous ecological success of ants. Here we show that the general principles regulating division of labour in ant colonies indeed allow the design of flexible, robust and effective robotic systems. Groups of robots using ant-inspired algorithms of decentralized control techniques foraged more efficiently and maintained higher levels of group energy than single robots. But the benefits of group living decreased in larger groups, most probably because of interference during foraging. Intriguingly, a similar relationship between group size and efficiency has been documented in social insects. Moreover, when food items were clustered, groups where robots could recruit other robots in an ant-like manner were more efficient than groups without information transfer, suggesting that group dynamics of swarms of robots may follow rules similar to those governing social insects
Character building in childrens’ online information behaviours: applying a virtue epistemology perspective to information literacy.
This paper advances our understanding of the theoretical and practical challenges of developing intellectual character in children’s online information behaviours. We argue that widely reported issues such as misinformation and disinformation extend IL education beyond considerations of ability to considerations of disposition, and highlight this as an understudied topic within IL education. We introduce the classical concept of intellectual character and discuss virtues traits in the IL context. Applying Baehr’s nine intellectual virtues to two commonly cited IL models, we evidence limited presence of virtues in IL models, and propose an important agenda for future research
The participatory medicine attitudes of general practitioners in Greece: an information behaviour perspective
General Practitioners (GPs) need to keep up with a wide range of medical conditions and at the same time closely interact with their patients to provide preventive care and health education. This requires effectively sourcing, utilizing, and sharing quality information with their patients as well as creating participatory and shared decision-making health environments. This paper explores the information seeking behaviour of GPs and their attitudes towards participatory medicine (PM). A questionnaire based survey with GPs in Greece, registered with the Hellenic Society of General Practitioners (HSGP) was conducted and included an exploration of three different information seeking dimensions (information needs, sources and barriers) that were associated with GPs' perceptions of PM. The survey results demonstrate an interplay of demographic and contextual factors in the choice of information sources and the barriers encountered and conclude that the effective utilization of online information sources is an essential condition for PM practices
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