Metal-binding studies for a de novo designed calcium-binding protein

To understand the key determinants in calcium-binding affinity,a calcium-binding site with pentagonal bipyramid geometry wasdesigned into a non-calcium-binding protein, domain 1 of CD2.This metal-binding protein has five mutations with a net chargein the coordination sphere of –5 and is termed DEEEE.Fluorescence resonance energy transfer was used to determinethe metal-binding affinity of DEEEE to the calcium analog terbium.The addition of protein concentration to Tb(III) solution resultsin a large enhancement of Tb(III) fluorescence due to energytransfer between terbium ions and aromatic residues in CD2-D1.In addition, both calcium and lanthanum compete with terbiumfor the same desired metal binding pocket. Our designed proteinexhibits a stronger affinity for Tb(III), with a K_d of 21 µM,than natural calcium-binding proteins with a similar Greek keyscaffold.     

Arsenic-sulfides confound anion exchange resin speciation of aqueous arsenic

A field-portable anion exchange resin method (often cited as the Ficklin method (1983)) has been extensively used to distinguish between dissolved arsenite (As(III)) and arsenate (As(V)) species in natural waters. As(III) occurs largely as As(OH)(3), which is uncharged at ca. pH 7, while As(V) is negatively charged and will sorb to the resin. However, we show that negatively charged As(III)-sulfide (thioarsenite) species, important at sulfide concentrations >10 microM, also bind to the anion exchange resins, and therefore might be interpreted incorrectly as As(V). Furthermore, we show that nitrogen-purging, which results in a conversion of As(III)-sulfides to arsenite, can be used to obtain accurate arsenic speciation when resins are used on sulfidic water samples.     

Macrophage-Dependent Interleukin-6-Production and Inhibition of IK Contributes to Acquired QT Prolongation in Lipotoxic Guinea Pig Heart

In the heart, the delayed rectifier K current, I_K, composed of the rapid (I_Kr) and slow (I_Ks) components contributes prominently to normal cardiac repolarization. In lipotoxicity, chronic elevation of pro-inflammatory cytokines may remodel I_K, elevating the risk for ventricular arrythmias and sudden cardiac death. We investigated whether and how the pro-inflammatory interleukin-6 altered I_K in the heart, using electrophysiology to evaluate changes in I_K in adult guinea pig ventricular myocytes. We found that palmitic acid (a potent inducer of lipotoxicity), induced a rapid (~24 h) and significant increase in IL-6 in RAW264.7 cells. PA-diet fed guinea pigs displayed a severely prolonged QT interval when compared to low-fat diet fed controls. Exposure to isoproterenol induced torsade de pointes, and ventricular fibrillation in lipotoxic guinea pigs. Pre-exposure to IL-6 with the soluble IL-6 receptor produced a profound depression of I_Kr and I_Ks densities, prolonged action potential duration, and impaired mitochondrial ATP production. Only with the inhibition of I_Kr did a proarrhythmic phenotype of I_Ks depression emerge, manifested as a further prolongation of action potential duration and QT interval. Our data offer unique mechanistic insights with implications for pathological QT interval in patients and vulnerability to fatal arrhythmias.     

Single-channel EEG measurement of engagement in virtual rehabilitation: a validation study

Virtual Reality - Stroke rehabilitation suffers from low levels of patient engagement, impeding recovery. Virtual rehabilitation (VR) approaches can improve patient outcomes; however, there is...     

Understanding the cortical specialization for horizontal disparity

Because the eyes are displaced horizontally, binocular vision is inherently anisotropic. Recent experimental work has uncovered evidence of this anisotropy in primary visual cortex (V1): neurons respond over a wider range of horizontal than vertical disparity, regardless of their orientation tuning. This probably reflects the horizontally elongated distribution of two-dimensional disparity experienced by the visual system, but it conflicts with all existing models of disparity selectivity, in which the relative response range to vertical and horizontal disparities is determined by the preferred orientation. Potentially, this discrepancy could require us to abandon the widely held view that processing in V1 neurons is initially linear. Here, we show that these new experimental data can be reconciled with an initial linear stage; we present two physiologically plausible ways of extending existing models to achieve this. First, we allow neurons to receive input from multiple binocular subunits with different position disparities (previous models have assumed all subunits have identical position and phase disparity). Then we incorporate a form of divisive normalization, which has successfully explained many response properties of V1 neurons but has not previously been incorporated into a model of disparity selectivity. We show that either of these mechanisms decouples disparity tuning from orientation tuning and discuss how the models could be tested experimentally. This represents the first explanation of how the cortical specialization for horizontal disparity may be achieved.     

An Exploration of Impact of Cognitive Elaboration on Learning in ISD Projects

Stakeholder learning has been considered crucial for effective participation and the success of information system development (ISD). However, little guidance has been offered as an operational method to facilitate learning in ISD settings. We argue that “cognitive elaboration” (CE) is a helpful strategy for developing effective learning in client–developer interactions in ISD efforts. Two types of learning are investigated: model-building (MB) and model-maintenance (MM). The current study investigated whether CE performed by stakeholders themselves in client–developer interaction led to their MB rather than MM learning. In addition, an alternative hypothesis has been explored: whether mere communication activities may induce learning. Fifty individuals in seven ongoing software development projects in four organizations were examined. For each project, two meetings in which clients and developers participated were observed. The empirical results demonstrated that stakeholders in an ISD process who have engaged in CE themselves are more likely to experience MB learning; and that mere communication does not account for MB learning. An insignificant link between CE and MM learning was found. This study deepens our understanding about IS–user interactions. Limitations of the current research and implications for future research are discussed.     

The MarineGrid project in Ireland with Webcom

The 1999–2007 Irish National Seabed Survey is one of the largest ocean floor mapping projects ever attempted. Its aim is to map the ocean floor of the Irish territorial waters (approximately $525000{\mathrm{km}}^2$). To date, the Geological Survey of Ireland has gathered in excess of 4 TB of multibeam sonar data from the Irish National Seabed, and this data set is expected to exceed 10 TB upon completion. The main challenge that arises from having so much data is how to extract accurate information given the size of the data set. Geological interpretation is carried out by visual inspection of bathymetric patterns. The size of this, and similar, data sets renders the extraction of knowledge by human observers infeasible. Consequently, the focus has turned to using artificial intelligence and computational methods for assistance. The commercial and environmental sensitivity of the data means that secure data processing and transmission are of paramount importance. This has lead to the creation of the MarineGrid project within the Grid-Ireland organisation. New methods have been developed for statistical analysis of bathymetric information specifically for automated geological interpretation of rock types on the sea floor and feature extraction from the sea floor. We present a discussion on how to provide Marine and Geological researchers convenient yet secure access to resources that make use of grid technologies including pre-written algorithms in order to exploit the Irish National Seabed Survey data archive.     

Viewing 3D TV over two months produces no discernible effects on balance,coordination or eyesight

With the rise in stereoscopic 3D media, there has been concern that viewing stereoscopic 3D (S3D) content could have long-term adverse effects, but little data are available. In the first study to address this, 28 households who did not currently own a 3D TV were given a new TV set, either S3D or 2D. The 116 members of these households all underwent tests of balance, coordination and eyesight, both before they received their new TV set, and after they had owned it for 2 months. We did not detect any changes which appeared to be associated with viewing 3D TV. We conclude that viewing 3D TV does not produce detectable effects on balance, coordination or eyesight over the timescale studied.

Practitioner Summary: Concern has been expressed over possible long-term effects of stereoscopic 3D (S3D). We looked for any changes in vision, balance and coordination associated with normal home S3D TV viewing in the 2 months after first acquiring a 3D TV. We find no evidence of any changes over this timescale.