Seventeen a-subunit isoforms of paramecium V-ATPase provide high specialization in localization and function

In the Paramecium tetraurelia genome, 17 genes encoding the 100-kDa-subunit (a-subunit) of the vacuolar-proton-ATPase were identified, representing by far the largest number of a-subunit genes encountered in any organism investigated so far. They group into nine clusters, eight pairs with >82% amino acid identity and one single gene. Green fluorescent protein-tagging of representatives of the nine clusters revealed highly specific targeting to at least seven different compartments, among them dense core secretory vesicles (trichocysts), the contractile vacuole complex, and phagosomes. RNA interference for two pairs confirmed their functional specialization in their target compartments: silencing of the trichocyst-specific form affected this secretory pathway, whereas silencing of the contractile vacuole complex-specific form altered organelle structure and functioning. The construction of chimeras between selected a-subunits surprisingly revealed the targeting signal to be located in the C terminus of the protein, in contrast with the N-terminal targeting signal of the a-subunit in yeast. Interestingly, some chimeras provoked deleterious effects, locally in their target compartment, or remotely, in the compartment whose specific a-subunit N terminus was used in the chimera.

When electronic management tools work - and don't work - in social-based distribution channels:a study of IT manufacturers and resellers

Electronic information tools have become increasingly popular with channel manufacturers in their efforts to manage resellers. Although these tools have been found to increase the efficiency of communications, researchers and practitioners alike have questioned their effectiveness. To investigate how top-down electronic information affects social channel relationships we consider the use of such tools in information technology distribution channels. Using electronic communications theory and channel governance theory we hypothesize that the usefulness of the tools is a function of the type of information inherent in each tool (demand creation information or supply fulfillment information) and the particular communications characteristics of this information.

Development and application of an electronic-manufacturing selection framework for SMEs

With a wide diversity of available technologies, it is extremely problematic for SMEs to identify, plan, prioritize and use the correct strategy. Electronic-manufacturing has been evolving for some time, but currently an effective planning framework to assist managers with implementing electronic-manufacturing planning is still lacking. A framework, built around three elements: the Balanced Scorecard, Quality Function Deployment and Value Chain Analysis, is proposed here to assist SMEs in managing complexity in e-manufacturing planning. A case study, carried out in Singapore, demonstrates the practicality and utility of the framework in the context of a real business environment. © World Scientific Publishing Company.

Differential localization of GABAA receptor subunits in relation to rat striatopallidal and pallidopallidal synapses

As a central integrator of basal ganglia function, the external segment of the globus pallidus (GP) plays a critical role in the control of voluntary movement. The GP is composed of a network of inhibitory GABA-containing projection neurons which receive GABAergic input from axons of the striatum (Str) and local collaterals of GP neurons. Here, using electrophysiological techniques and immunofluorescent labeling we have investigated the differential cellular distribution of a1, a2 and a3 GABAA receptor subunits in relation to striatopallidal (Str-GP) and pallidopallidal (GP-GP) synapses. Electrophysiological investigations showed that zolpidem (100 nm; selective for the a1 subunit) increased the amplitude and the decay time of both Str-GP and GP-GP IPSCs, indicating the presence of the a1 subunits at both synapses. However, the application of drugs selective for the a2, a3 and a5 subunits (zolpidem at 400 nm, L-838,417 and TP003) revealed differential effects on amplitude and decay time of IPSCs, suggesting the nonuniform distribution of non-a1 subunits. Immunofluorescence revealed widespread distribution of the a1 subunit at both soma and dendrites, while double- and triple-immunofluorescent labeling for parvalbumin, enkephalin, gephyrin and the ?2 subunit indicated strong immunoreactivity for GABAAa3 subunits in perisomatic synapses, a region mainly targeted by local axon collaterals. In contrast, immunoreactivity for synaptic GABAAa2 subunits was observed in dendritic compartments where striatal synapses are preferentially located. Due to the kinetic properties which each GABAAa subunit confers, this distribution is likely to contribute differentially to both physiological and pathological patterns of activity.

Electronic commerce adoption:a study of business-to-business practice in Saudi Arabia

Electronic commerce (e-commerce) has become an increasingly important initiative among organisations. The factors affecting adoption decisions have been well-documented, but there is a paucity of empirical studies that examine the adoption of e-commerce in developing economies in the Arab world. The aim of this study is to provide insights into the salient e-commerce adoption issues by focusing on Saudi Arabian businesses. Based on the Technology-Organisational-Environmental framework, an integrated research model was developed that explains the relative influence of 19 known determinants. A measurement scale was developed from prior empirical studies and revised based on feedback from the pilot study. Non-interactive adoption, interactive adoption and stabilisation of e-commerce adoption were empirically investigated using survey data collected from Saudi manufacturing and service companies. Multiple discriminant function analysis (MDFA) was used to analyse the data and research hypotheses. The analysis demonstrates that (1) regarding the non-interactive adoption of e-commerce, IT readiness, management team support, learning orientation, strategic orientation, pressure from business partner, regulatory and legal environment, technology consultants‘ participation and economic downturn are the most important factors, (2) when e-commerce interactive adoption is investigated, IT readiness, management team support, regulatory environment and technology consultants‘ participation emerge as the strongest drivers, (3) pressure from customers may not have much effect on the non-interactive adoption of e-commerce by companies, but does significantly influence the stabilisation of e-commerce use by firms, and (4) Saudi Arabia has a strong ICT infrastructure for supporting e-commerce practices. Taken together, these findings on the multi-dimensionality of e-commerce adoption show that non-interactive adoption, interactive adoption and stabilisation of e-commerce are not only different measures of e-commerce adoption, but also have different determinants. Findings from this study may be valuable for both policy and practice as it can offer a substantial understanding of the factors that enhance the widespread use of B2B e-commerce. Also, the integrated model provides a more comprehensive explanation of e-commerce adoption in organisations and could serve as a foundation for future research on information systems.

Form follows function:model-driven engineering for clinical trials

We argue that, for certain constrained domains, elaborate model transformation technologies-implemented from scratch in general-purpose programming languages-are unnecessary for model-driven engineering; instead, lightweight configuration of commercial off-the-shelf productivity tools suffices. In particular, in the CancerGrid project, we have been developing model-driven techniques for the generation of software tools to support clinical trials. A domain metamodel captures the community's best practice in trial design. A scientist authors a trial protocol, modelling their trial by instantiating the metamodel; customized software artifacts to support trial execution are generated automatically from the scientist's model. The metamodel is expressed as an XML Schema, in such a way that it can be instantiated by completing a form to generate a conformant XML document. The same process works at a second level for trial execution: among the artifacts generated from the protocol are models of the data to be collected, and the clinician conducting the trial instantiates such models in reporting observations-again by completing a form to create a conformant XML document, representing the data gathered during that observation. Simple standard form management tools are all that is needed. Our approach is applicable to a wide variety of information-modelling domains: not just clinical trials, but also electronic public sector computing, customer relationship management, document workflow, and so on. © 2012 Springer-Verlag.

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality:a systematic review

Objectives: to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes.Design: electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible.Results: forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good.Conclusion: medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.

Impact of reduced complexity inverse Volterra series transfer function-based nonlinear equalizer in coherent OFDM systems for next-generation core networks

A modern electronic nonlinearity equalizer (NLE) based on inverse Volterra series transfer function (IVSTF) with reduced complexity is applied on coherent optical orthogonal frequency-division multiplexing (CO-OFDM) signals for next-generation long- and ultra-long-haul applications. The OFDM inter-subcarrier crosstalk effects are explored thoroughly using the IVSTF-NLE and compared with the case of linear equalization (LE) for transmission distances of up to 7000 km. © 2013 IEEE.