Magnetic flux jumps in textured Bi2Sr2CaCu2O(8+d)

Magnetic flux jumps in textured Bi2Sr2CaCu2O(8+d) have been studied by means of magnetization measurements in the temperature range between 1.95 K and Tc, in an external magnetic field up to 9 T. Flux jumps were found in the temperature range 1.95 K - 6 K, with the external magnetic field parallel to the c axis of the investigated sample. The effect of sample history on magnetic flux jumping was studied and it was found to be well accounted for by the available theoretical models. The magnetic field sweep rate strongly influences the flux jumping and this effect was interpreted in terms of the influence of both flux creep and the thermal environment of the sample. Strong flux creep was found in the temperature and magnetic field range where flux jumps occur suggesting a relationship between the two. The heat exchange conditions between the sample and the experimental environment also influence the flux jumping behavior. Both these effects stabilize the sample against flux instabilities, and this stabilizing effect increases with decreasing magnetic field sweep rate. Demagnetizing effects are also shown to have a significant influence on flux jumping.Comment: 10 pages, 6 figures, RevTeX4, submitted to Phys. Rev.

A Caenorhabditis elegans assay of seizure-like activity optimised for identifying antiepileptic drugs and their mechanisms of action

BACKGROUND: Epilepsy affects around 1% of people, but existing antiepileptic drugs (AEDs) only offer symptomatic relief and are ineffective in approximately 30% of patients. Hence, new AEDs are sorely needed. However, a major bottleneck is the low-throughput nature of early-stage AED screens in conventional rodent models. This process could potentially be expedited by using simpler invertebrate systems, such as the nematode Caenorhabditis elegans. NEW METHOD: Head-bobbing convulsions were previously reported to be inducible by pentylenetetrazol (PTZ) in C. elegans with loss-of-function mutations in unc-49, which encodes a GABAA receptor. Given that epilepsy-linked mutations in human GABAA receptors are well documented, this could represent a clinically-relevant system for early-stage AED screens. However, the original agar plate-based assay is unsuited to large-scale screening and has not been validated for identifying AEDs. Therefore, we established an alternative streamlined, higher-throughput approach whereby mutants were treated with PTZ and AEDs via liquid-based incubation. RESULTS: Convulsions induced within minutes of PTZ exposure in unc-49 mutants were strongly inhibited by the established AED ethosuximide. This protective activity was independent of ethosuximide's suggested target, the T-type calcium channel, as a null mutation in the worm cca-1 ortholog did not affect ethosuximide's anticonvulsant action. COMPARISON WITH EXISTING METHOD: Our streamlined assay is AED-validated, feasible for higher throughput compound screens, and can facilitate insights into AED mechanisms of action. CONCLUSIONS: Based on an epilepsy-associated genetic background, this C. elegans unc-49 model of seizure-like activity presents an ethical, higher throughput alternative to conventional rodent seizure models for initial AED screens

Regulation of exocytosis by protein kinase C

PKC (protein kinase C) has been known for many years to modulate regulated exocytosis in a wide variety of cell types. in neurons and neuroendocrine cells, PKC regulates several different stages of the exocytotic process, suggesting that these multiple actions of PKC are mediated by phosphorylation of distinct protein targets. In recent years, a variety of exocytotic proteins have been identified as PKC substrates, the best characterized of which are SNAP-25 (25 kDa synaptosome-associated protein) and Munc18. In the present study, we review recent evidence suggesting that site-specific phosphorylation of SNAP-2S and Munc18 by PKC regulates distinct stages of exocytosis.</p

When worlds collide: developing game design partnerships in universities

A growing body of evidence suggests that relevant, well-designed simulations can make a valuable contribution to students' experiences in training and education and go some way toward meeting the expectations of students who have grown up with immersive, computer-mediated games. Within universities, many barriers exist that may prevent the effective development of this work, in part because of the nature of the traditional roles of both academics and developers who undertake these activities. Through a discussion of the experiences of working within a successful cross-functional team, the authors discuss the practice of developing an innovative eLearning simulation tool for an undergraduate course and how the challenges of combining the developer and educationalist roles were overcome. By synthesizing theories in educational philosophy and game design processes, a conceptual framework for ensuring quality in creative education projects is outlined that may be applied to the development of eLearning and adaptive game projects