Prevention of Glaucoma-Induced Retinal Ganglion Cell Loss Using Alpha7 nAChR Agonists

In this study, the neuroprotective effect of various nicotinic alpha7 acetylcholine receptor agonists in an in-vivo model of glaucoma using adult Long Evans rats was analyzed. Glaucoma-like conditions were induced in the eyes of Long Evans rats after injection of hypertonic saline into episcleral veins to create scar tissue and increase the animal’s intraocular pressure. This procedure produced significant loss of retinal ganglion cells within one month and was associated with an increase of intraocular pressure. Using this model system, various alpha7 nicotinic acetylcholine receptor (a7 nAChR) agonists were applied at different doses as eye drops to the right eye of adult Long Evans rats while the left eye was left as an internal control. The a7 nAChR agonists used in this study prevented loss of RGCs in a dose dependent manner after the procedure to induce glaucoma-like conditions. PHA-543613 and PNU- 282987 provided the largest degree of RGC survival after inducing glaucomalike conditions, followed by nicotine, SEN 12333, tropisetron, 3-Bromocytisine and DMAB. To provide evidence that neuroprotection of RGCs was mediated through activation of a7 nAChR, in some studies different concentrations of the a7 nAChR antagonist, MLA, was intravitreally injected into experimentally treated eyes before initiation of eye drops and the procedure to induce glaucoma-like conditions. In the presence of MLA, RGC neuroprotection was blocked. Results from these studies suggest that selective a7 nAChR agonists may be used in future therapeutic treatments for glaucoma or other CNS diseases associated with a7 nAChRs

Toward a script theory of guidance in computer-supported collaborative learning

This article presents an outline of a script theory of guidance for computer-supported collaborative learning (CSCL). With its four types of components of internal and external scripts (play, scene, role, and scriptlet) and seven principles, this theory addresses the question how CSCL practices are shaped by dynamically re-configured internal collaboration scripts of the participating learners. Furthermore, it explains how internal collaboration scripts develop through participation in CSCL practices. It emphasizes the importance of active application of subject matter knowledge in CSCL practices, and it prioritizes transactive over non-transactive forms of knowledge application in order to facilitate learning. Further, the theory explains how external collaboration scripts modify CSCL practices and how they influence the development of internal collaboration scripts. The principles specify an optimal scaffolding level for external collaboration scripts and allow for the formulation of hypotheses about the fading of external collaboration scripts. Finally, the article points towards conceptual challenges and future research questions

Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme

Organophosphorus (OP) nerve agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart nerve agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with nerve agent as a guide, a pair of histidine and glutamic acid residues were designed proximal to the enzyme's native catalytic triad. The resultant variant protein demonstrated significantly increased rates of reactivation following exposure to sarin, soman, and cyclosarin. Importantly, the addition of these residues did not alter the high affinity binding of nerve agents to this protein. Thus, using two amino acid substitutions, a novel enzyme was created that efficiently converted a group of hemisubstrates, compounds that can start but not complete a reaction cycle, into bona fide substrates. Such approaches may lead to novel countermeasures for nerve agent poisoning

Stability of rotating states in a weakly-interacting Bose-Einstein condensate

We investigate the lowest state of a rotating, weakly-interacting Bose-Einstein condensate trapped in a harmonic confining potential that is driven by an infinitesimally asymmetric perturbation. Although in an axially-symmetric confining potential the gas has an axially-symmetric single-particle density distribution, we show that in the presence of the small asymmetric perturbation its lowest state is the one given by the mean-field approximation, which is a broken-symmetric state. We also estimate the rate of relaxation of angular momentum when the gas is no longer driven by the asymmetric perturbation and identify two regimes of "slow" and "fast" relaxation. States of certain symmetry are found to be more robust.Comment: 6 pages, RevTe

High accuracy calculation of 6s -> 7s parity nonconserving amplitude in Cs

We calculated the parity nonconserving (PNC) 6s -> 7s amplitude in Cs. In the Dirac-Coulomb approximation our result is in a good agreement with other calculations. Breit corrections to the PNC amplitude and to the Stark-induced amplitude $\beta$ are found to be -0.4% and -1% respectively. The weak charge of $^{133}$Cs is $Q_W=-72.5 \pm 0.7$ in agreement with the standard model.Comment: 4 pages, LaTeX2e, uses revtex4.cls, submitted to PR

Design approaches in technology enhanced learning

Design is a critical to the successful development of any interactive learning environment (ILE). Moreover, in technology enhanced learning (TEL), the design process requires input from many diverse areas of expertise. As such, anyone undertaking tool development is required to directly address the design challenge from multiple perspectives. We provide a motivation and rationale for design approaches for learning technologies that draws upon Simon's seminal proposition of Design Science (Simon, 1969). We then review the application of Design Experiments (Brown, 1992) and Design Patterns (Alexander et al., 1977) and argue that a patterns approach has the potential to address many of the critical challenges faced by learning technologists

Is a Trapped One-Dimensional Bose Gas a Luttinger Liquid?

The low-energy fluctuations of a trapped, interacting quasi one-dimensional Bose gas are studied. Our considerations apply to experiments with highly anisotropic traps. We show that under suitable experimental conditions the system can be described as a Luttinger liquid. This implies that the correlation function of the bosons decays algebraically preventing Bose-Einstein condensation. At significantly lower temperatures a finite size gap destroys the Luttinger liquid picture and Bose-Einstein condensation is again possible.Comment: 4 pages (revtex), 1 figure (eps file