The missense mutation in Abcg5 gene in spontaneously hypertensive rats (SHR) segregates with phytosterolemia but not hypertension

BACKGROUND: Sitosterolemia is a recessively inherited disorder in humans that is associated with premature atherosclerotic disease. Mutations in ABCG5 or ABCG8, comprising the sitosterolemia locus, STSL, are now known to cause this disease. Three in-bred strains of rats, WKY, SHR and SHRSP, are known to be sitosterolemic, hypertensive and they carry a missense 'mutation' in a conserved residue of Abcg5, Gly583Cys. Since these rat strains are also know to carry mutations at other genetic loci and the extent of phytosterolemia is only moderate, it is important to verify that the mutations in Abcg5 are causative for phytosterolemia and whether they contribute to hypertension. METHODS: To investigate whether the missense change in Abcg5 is responsible for the sitosterolemia we performed a segregation analysis in 103 F2 rats from a SHR × SD cross. Additionally, we measured tail-cuff blood pressure and measured intestinal lipid transport to identify possible mechanisms whereby this mutation causes sitosterolemia. RESULTS: Segregation analysis showed that the inheritance of the Gly583Cys mutation Abcg5 segregated with elevated plant sterols and this pattern was recessive, proving that this genetic change is responsible for the sitosterolemia in these rat strains. Tail-cuff monitoring of blood pressure in conscious animals showed no significant differences between wild-type, heterozygous and homozygous mutant F2 rats, suggesting that this alteration may not be a significant determinant of hypertension in these rats on a chow diet. CONCLUSION: This study shows that the previously identified Gly583Cys change in Abcg5 in three hypertension-susceptible rats is responsible for the sitosterolemia, but may not be a major determinant of blood pressure in these rats

(Digital) tools as professional and generational identity badges in the Chinese creative industries

Animators, architects, designers, and others active in the Chinese creative industries are expert users of tools, both analog and digital. Performances of expert tool use (the wearing of professional identity badges) are strategic ways of signaling creativity understood as sets of skills and character traits essential for attracting work projects but also for professional identity formation. Analogue tools are generally associated with creative openness and fluidity whereas digital tools are discursively constructed as a technological other to the analogue. ‘Older’ creatives (born before 1980) tend to apply some of the media-inflected discourse around the balinghou generation (born 1980–1989) to their younger competitors, including an assumed affinity with digital media and technologies (the pinning on of a generational identity badge). Such generational assumptions can have the effect of reinforcing project hierarchies and denying expert users of digital tools their claims to creativity

Learning curves: analysing pace and challenge in four successful puzzle games

The pace at which challenges are introduced in a game has long been identified as a key determinant of both the enjoyment and difficulty experienced by game players, and their ability to learn from game play. In order to understand how to best pace challenges in games, there is great value in analysing games already demonstrated as highly engaging. Play-through videos of four puzzle games (Portal, Portal 2 Co-operative mode, Braid and Lemmings), were observed and analysed using metrics derived from a behavioural psychology understanding of how people solve problems. Findings suggest that; 1) the main skills learned in each game are introduced separately, 2) through simple puzzles that require only basic performance of that skill, 3) the player has the opportunity to practice and integrate that skill with previously learned skills, and 4) puzzles increase in complexity until the next new skill is introduced. These data provide practical guidance for designers, support contemporary thinking on the design of learning structures in games, and suggest future directions for empirical research

Endogenous fantasy and learning in digital games.

Many people believe that educational games are effective because they motivate children to actively engage in a learning activity as part of playing the game. However, seminal work by Malone (1981), exploring the motivational aspects of digital games, concluded that the educational effectiveness of a digital game depends on the way in which learning content is integrated into the fantasy context of the game. In particular, he claimed that content which is intrinsically related to the fantasy will produce better learning than that which is merely extrinsically related. However, this distinction between intrinsic and extrinsic (or endogenous and exogenous) fantasy is a concept that has developed a confused standing over the following years. This paper will address this confusion by providing a review and critique of the empirical and theoretical foundations of endogenous fantasy, and its relevance to creating educational digital games. Substantial concerns are raised about the empirical basis of this work and a theoretical critique of endogenous fantasy is offered, concluding that endogenous fantasy is a misnomer, in so far as the "integral and continuing relationship" of fantasy cannot be justified as a critical means of improving the effectiveness of educational digital games. An alternative perspective on the intrinsic integration of learning content is described, incorporating game mechanics, flow and representations

Generalised Player Modelling : Why Artificial Intelligence in Games Should Incorporate Meaning, with a Formalism for so Doing

General game-playing artificial intelligence (AI) has recently seen important advances due to the various techniques known as ‘deep learning’. However, in terms of human-computer interaction, the advances conceal a major limitation: these algorithms do not incorporate any sense of what human players find meaningful in games. I argue that adaptive game AI will be enhanced by a generalised player model, because games are inherently human artefacts which require some encoding of the human perspective in order to respond naturally to individual players. The player model provides constraints on the adaptive AI, which allow it to encode aspects of what human players find meaningful. I propose that a general player model requires parameters for the subjective experience of play, including: player psychology, game structure, and actions of play. I argue that such a player model would enhance efficiency of per-game solutions, and also support study of game-playing by allowing (within-player) comparison between games, or (within-game) comparison between players (human and AI). Here we detail requirements for functional adaptive AI, arguing from first-principles drawn from games research literature, and propose a formal specification for a generalised player model based on our ‘Behavlets’ method for psychologically-derived player modelling.Peer reviewe

Potential of EPR spin-trapping to investigate in situ free radicals generation from skin allergens in reconstructed human epidermis: cumene hydroperoxide as proof of concept

The first step in the development of skin sensitisation to a chemical, and in the elicitation offurther allergic contact dermatitis (ACD), is the binding of the allergen to skin proteins after pene-trating into the epidermis. The so-formed antigenic adduct is then recognised by the immunesystem as foreign to the body. Sensitising organic hydroperoxides derived from autoxidation ofnatural terpenes are believed to form antigens through radical-mediated mechanisms, althoughthis has not yet been established. So far,in vitroinvestigations on reactive radical intermediatesderived from these skin sensitisers have been conducted in solution, yet with experimental condi-tions being far away from real-life sensitisation. Herein, we report for the first time, the potentialuse of EPR spin-trapping to study thein situgeneration of free radicals derived from cumenehydroperoxide CumOOH in a 3D reconstructed human epidermis (RHE) model, thus much closerto what may happenin vivo. Among the undesirable effects associated with dermal exposure toCumOOH, it is described to cause allergic and irritant dermatitis, being reported as a significantsensitiser. We considered exploiting the usage of spin-trap DEPMPO as an extensive view of allsort of radicals derived from CumOOH were observed all at once in solution. We showed that inthe EpiskinTMRHE model, both by incubating in the assay medium and by topical application,carbon radicals are mainly formed by redox reactions suggesting the key role of CumOOH-derived carbon radicals in the antigen formation process

“It’s like my life but more, and better!” - Playing with the Cathaby Shark Girls: MMORPGs, young people and fantasy-based social play

This article is available open access through the publisher’s website at the link below. Copyright @ 2011 A B Academic Publishers.Digital technology has opened up a range of new on-line leisure spaces for young people. Despite their popularity, on-line games and Massive Multiplayer Online Role Playing Games in particular are still a comparatively under-researched area in the fields of both Education and more broadly Youth Studies. Drawing on a Five year ethnographic study, this paper considers the ways that young people use the virtual spaces offered by MMORPGs. This paper suggests that MMORPGs represent significant arenas within which young people act out a range of social narratives through gaming. It argues that MMORPG have become important fantasy spaces which offer young people possibilities to engage in what were formally material practices. Although this form of play is grounded in the everyday it also extends material practices and offers new and unique forms of symbolic experimentation, thus I argue that game-play narratives cannot be divorced from the everyday lives of their participants

Teacher interventions in students’ collaborative work in a technology-rich educational makerspace

This study reports on an investigation of teacher interventions in students' collaborative work in an educational makerspace. We draw on a qualitative analysis of video data on teacher-student interaction derived from 94 students (aged 9-12) and their teachers in a Finnish school. The results show that the teacher interventions were both student- and teacher-initiated. Three leading teacher intervention strategies were identified, namely authoritative, orchestrating and unleashing which emerged in teacher-student interactions dealing with conceptual, procedural, technological, behavioural and motivational issues. The study demonstrates the demands makerspaces pose for teacher-student interaction, and how moving from authoritative to collaborative interaction requires collective efforts and cultural change.Peer reviewe