Epac and the high affinity rolipram binding conformer of PDE4 modulate neurite outgrowth and myelination using an in vitro spinal cord injury model

<b>Background and Purpose</b><p></p> cAMP and pharmacological inhibition of PDE4, which degrades it, are promising therapeutic targets for the treatment of spinal cord injury (SCI). Using our previously described in vitro SCI model, we studied the mechanisms by which cAMP modulators promote neurite outgrowth and myelination using enantiomers of the PDE4-specific inhibitor rolipram and other modulators of downstream signalling effectors.<p></p> <b>Experimental Approach</b><p></p> Rat mixed neural cell myelinating cultures were cut with a scalpel and treated with enantiomers of the PDE4-specific inhibitor rolipram, Epac agonists and PKA antagonists. Neurite outgrowth, density and myelination were assessed by immunocytochemistry and cytokine levels analysed by qPCR.<p></p> <b>Key Results</b><p></p> Inhibition of the high-affinity rolipram-binding state (HARBS), rather than the low-affinity rolipram binding state (LARBS) PDE4 conformer promoted neurite outgrowth and myelination. These effects were mediated through the activation of Epac and not through PKA. Expression of the chemokine CXCL10, known to inhibit myelination, was markedly elevated in astrocytes after Rho inhibition and this was blocked by inhibition of Rho kinase or PDE4.<p></p> <b>Conclusions and Implications</b><p></p> PDE4 inhibitors targeted at the HARBS conformer or Epac agonists may provide promising novel targets for the treatment of SCI. Our study demonstrates the differential mechanisms of action of these compounds, as well as the benefit of a combined pharmacological approach and highlighting potential promising targets for the treatment of SCI. These findings need to be confirmed in vivo

Agreement between patient and proxy of life quality after stroke

published_or_final_versio

Mobile target tracking using a reconfigurable low earth orbit constellation

Traditional Earth-observing satellite constellations must preselect orbits to match established mission objectives, inherently limiting the capability of the system to respond to dynamic events. A more flexible approach to constellation design which maneuvers satellites to new orbits throughout the mission lifetime can enable the tracking of mobile targets; such a concept will be explored and evaluated in the following paper. Currently, an existing approach for creating a reconfigurable constellation of satellites (ReCon) demonstrates some increased functionality. However, the repeating ground track (RGT) orbits used are only well-suited for static ground targets (i.e. particular latitude and longitude points) as they are defined by their repetitious passes over the particular points on the globe; inherently these orbits are not ideal for tracking mobile targets such as ships, oil spills, hurricanes, and other weather events. By addressing this gap and designing the constellation to follow these mobile targets, data return can be of higher quality and quantity leading toward improved predictions of future movements. Traditional non-maneuverable satellites may of course capture mobile feature data; however, the quality and quantity of data returned is driven by the satellites’ orbits which were not designed for the particular mobile target. A proposed concept of operations that models possible sequential satellite maneuvers as a graph has shown promise for tracking mobile targets in the case of a single satellite. In the following paper, this concept is further explored by the addition of an optimizer to this method, applied to both a single satellite and a constellation of maneuverable satellites, like ReCon. Results for a tropical storm case study indicate that with relatively low amounts of delta-V per satellite, many possible maneuver combinations are found which result in improved accesses with greater total access time and closer passes. Trade-offs are shown between total target access time, mean distance to targets upon access, and total delta-V used. The performance of increased constellation size is also explored. By having satellites dynamically respond to mobile targets such as hurricanes, satellite imagery and remote sensing can be of better quality and even contribute to better predictions for developing storms

The Integration of Computer Technology in Small Businesses

 In an effort to more fullv  understand the use of computers and information technology in the small business  sector, a survey was conducted of small business owners in the state of South Carolina. Based on this survey, the present study investigates  the extent of computer and information technology integration in small businesses, identifies the major computer applications used by small business, and explores the use of e-mail and Internet technology by small businesses. The authors conclude that small business owners do not sufficiently take advantage of computers and information technology  for  either  operational  or  strategic assistance,  or for   comunications  and promotion

Assessing the Importance of Brand Equity in Health Services Marketing Through the Impact of Acquired Goodwill on Stockholder Returns

The growing importance of brand equity is widely recognized by researchers and business strategists alike. As such, creative new ways to capture the value of this intangible asset must be devised and tested. The current study uses acquired goodwill as a surrogate indicator of brand equity and looks at the importance of brand equity for firms in the health services industry by measuring the impact of acquired goodwill on stockholder returns. The findings indicate that acquired goodwill and stockholder returns appear to be significantly and positively related to each other. In addition, firms that have higher than average amounts of goodwill relative to total assets differ significantly in terms of stockholder returns than those that have relatively little investment in goodwill. Finally, the study indicates that the impact of goodwill on investor returns is highest for firms operating in one specific industry sub-sector, the market for home health services

Formation of a quasicrystalline Pb monolayer on the ten-fold surface of the decagonal Al-Ni-Co quasicrystal

Lead has been deposited on the ten-fold surface of decagonal Al72Ni11Co17 to form an epitaxial quasicrystalline single-element monolayer. The overlayer grows through nucleation of nanometer-sized irregular islands and the coverage saturates at 1 ML. The overlayer is well-ordered quasiperiodically as evidenced by LEED and Fourier transforms of STM images. Annealing the film to 600 K improves the structural quality, but causes the evaporation of some material such that the film develops pores. Electronic structure measurements using X-ray photoemission spectroscopy indicate that the chemical interaction of the Pb atoms with the substrate is weak.Comment: 12 pages, 5 figure

Nuclear alpha-clustering, superdeformation, and molecular resonances

Nuclear alpha-clustering has been the subject of intense study since the advent of heavy-ion accelerators. Looking back for more than 40 years we are able today to see the connection between quasimolecular resonances in heavy-ion collisions and extremely deformed states in light nuclei. For example superdeformed bands have been recently discovered in light N=Z nuclei such as $^{36}$Ar, $^{40}$Ca, $^{48}$Cr, and $^{56}$Ni by $\gamma$-ray spectroscopy. The search for strongly deformed shapes in N=Z nuclei is also the domain of charged-particle spectroscopy, and our experimental group at IReS Strasbourg has studied a number of these nuclei with the charged particle multidetector array {\sc Icare} at the {\sc Vivitron} Tandem facility in a systematical manner. Recently the search for $\gamma$-decays in $^{24}$Mg has been undertaken in a range of excitation energies where previously nuclear molecular resonances were found in $^{12}$C+$^{12}$C collisions. The breakup reaction $^{24}$Mg$+^{12}$C has been investigated at E$_{lab}$($^{24}$Mg) = 130 MeV, an energy which corresponds to the appropriate excitation energy in $^{24}$Mg for which the $^{12}$C+$^{12}$C resonance could be related to the breakup resonance. Very exclusive data were collected with the Binary Reaction Spectrometer in coincidence with {\sc Euroball IV} installed at the {\sc Vivitron}.Comment: 10 pages, 4 eps figures included. Invited Talk 10th Nuclear Physics Workshop Marie and Pierre Curie, Kazimierz Dolny Poland, Sep. 24-28, 2003; To be published in International Journal of Modern Physics

An integrated approach for analysing and assessing the performance of virtual learning groups

Collaborative distance learning involves a variety of elements and factors that have to be considered and measured in order to analyse and assess group and individual performance more effectively and objectively. This paper presents an approach that integrates qualitative, social network analysis (SNA) and quantitative techniques for evaluating online collaborative learning interactions. Integration of various different data sources, tools and techniques provides a more complete and robust framework for group modelling and guarantees a more efficient evaluation of group effectiveness and individual competence. Our research relies on the analysis of a real, long-term, complex collaborative experience, which is initially evaluated in terms of principled criteria and a basic qualitative process. At the end of the experience, the coded student interactions are further analysed through the SNA technique to assess participatory aspects, identify the most effective groups and the most prominent actors. Finally, the approach is contrasted and completed through a statistical technique which sheds more light on the results obtained that far. The proposal draws a well-founded line toward the development of a principled framework for the monitoring and analysis of group interaction and group scaffolding which can be considered a major issue towards the actual application of the CSCL proposals to real classrooms.Peer ReviewedPostprint (author's final draft

A Methodology Towards Measuring the Strategic Profile of First-Mover Firms in Industrial Markets

This study goes beyond most previous research on first-mover advantages by examining the broader concept of strategic marketing initiative. Specifically, a measurement scale was developed to assess the full extent of a firm\u27s first-mover efforts. A total of 1200 firms were surveyed, with a response rate of 12.2%. The Strategic Marketing Initiative Scale developed exhibited high reliability, and has application in assisting management in recognizing marketing areas for first mover advantages. This can result in better timing of decisions about the strategy of when to act, contributing to the ability to create a competitive advantage around marketing initiatives

Assessing the Importance of Brand Equity in Health Services Marketing Through the Impact of Acquired Goodwill on Stockholder Returns

The growing importance of brand equity is widely recognized by researchers and business strategists alike. As such, creative new ways to capture the value of this intangible asset must be devised and tested. The current study uses acquired goodwill as a surrogate indicator of brand equity and looks at the importance of brand equity for firms in the health services industry by measuring the impact of acquired goodwill on stockholder returns. The findings indicate that acquired goodwill and stockholder returns appear to be significantly and positively related to each other. In addition, firms that have higher than average amounts of goodwill relative to total assets differ significantly in terms of stockholder returns than those that have relatively little investment in goodwill. Finally, the study indicates that the impact of goodwill on investor returns is highest for firms operating in one specific industry sub-sector, the market for home health services