The role of plasma membrane STIM1 and Ca(2+)entry in platelet aggregation. STIM1 binds to novel proteins in human platelets.

Ca(2+) elevation is essential to platelet activation. STIM1 senses Ca(2+) in the endoplasmic reticulum and activates Orai channels allowing store-operated Ca(2+) entry (SOCE). STIM1 has also been reported to be present in the plasma membrane (PM) with its N-terminal region exposed to the outside medium but its role is not fully understood. We have examined the effects of the antibody GOK/STIM1, which recognises the N-terminal region of STIM1, on SOCE, agonist-stimulated Ca(2+) entry, surface exposure, in vitro thrombus formation and aggregation in human platelets. We also determined novel binding partners of STIM1 using proteomics. The dialysed GOK/STIM1 antibody failed to reduced thapsigargin- and agonist-mediated Ca(2+) entry in Fura2-labelled cells. Using flow cytometry we detect a portion of STIM1 to be surface-exposed. The dialysed GOK/STIM1 antibody reduced thrombus formation by whole blood on collagen-coated capillaries under flow and platelet aggregation induced by collagen. In immunoprecipitation experiments followed by proteomic analysis, STIM1 was found to extract a number of proteins including myosin, DOCK10, thrombospondin-1 and actin. These studies suggest that PM STIM1 may facilitate platelet activation by collagen through novel interactions at the plasma membrane while the essential Ca(2+)-sensing role of STIM1 is served by the protein in the ER.

Assessing pragmatic interoperability of information systems from a semiotic perspective

Most of studies on interoperability of systems integration focus on technical and semantic levels, but hardly extend investigations on pragmatic level. Our past work has addressed pragmatic interoperability, which is concerned with the relationship between signs and the potential behaviour and intention of responsible agents. We also define the pragmatic interoperability as a level concerning with the aggregation and optimisation of various business processes for achieving intended purposes of different information systems. This paper, as the extension of our previous research, is to propose an assessment method for measuring pragmatic interoperability of information systems. We firstly propose interoperability analysis framework, which is based on the concept of semiosis. We then develop pragmatic interoperability assessment process from two dimensions including six aspects (informal, formal, technical, substantive, communication, and control). We finally illustrate the assessment process in an example.

Effects of drugs that potentiate GABA on extinction of positively-reinforced operant behaviour

Extinction following positively reinforced operant conditioning reduces response frequency, at least in part through the aversive or frustrative effects of non-reinforcement. According to J.A. Gray's theory, non-reinforcement activates the behavioural inhibition system which in turn causes anxiety. As predicted, anxiolytic drugs including benzodiazepines affect the operant extinction process. Recent studies have shown that reducing GABA-mediated neurotransmission retards extinction of aversive conditioning. We have shown in a series of studies that anxiolytic compounds that potentiate GABA facilitate extinction of positively reinforced fixed-ratio operant behaviour in C57B1/6 male mice. This effect does not occur in the early stages of extinction, nor is it dependent on cumulative effects of the compound administered. Potentiation of GABA at later stages has the effect of increasing sensitivity to the extinction contingency and facilitates the inhibition of the behaviour that is no longer required. The GABAergic hypnotic, zolpidem, has the same selective effects on operant extinction in this procedure. The effects of zolpidem are not due to sedative action. There is evidence across our series of experiments that different GABA-A subtype receptors are involved in extinction facilitation and anxiolysis. Consequently, this procedure may not be an appropriate model for anxiolytic drug action, but it may be a useful technique for analysing the neural bases of extinction and designing therapeutic interventions in humans where failure to extinguish inappropriate behaviours can lead to pathological conditions such as post-traumatic stress disorder.

Effects of chlordiazepoxide on extinction and re-acquisition of operant behaviour in mice

Relatively little is known about the role of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in extinction of appetitively motivated tasks. The benzodiazepine (BZ) chlordiazepoxide (CDP) was administered during extinction and re-acquisition of lever pressing by mice following food reinforced discrete-trial fixed-ratio 5 (FR-5) training. Typical FR behaviour was established during baseline training and persisted for several extinction sessions. There were 15 extinction sessions in all, followed by six re-acquisition sessions where food reinforcement was re-introduced. In a 2x2x2 between-group design, CDP (15 mg/kg) or vehicle injections were given prior to either the last two food reinforcement sessions and the first 10 extinction sessions, or the final five extinction sessions, or the six re-acquisition sessions. Initially CDP had no effect on the rate of extinction, but after several extinction sessions it significantly facilitated it. Surprisingly, if CDP was administered only after several sessions of extinction, it immediately produced facilitation. Thus the delayed effects of CDP are not due to drug accumulation. These data suggest that some neural change must occur before CDP can affect extinction processes. In re-acquisition sessions, CDP facilitated the reinstatement of food-reinforced lever pressing. Implications for neural and behavioural accounts of operant extinction are discussed.

Subtype-selective GABAergic drugs facilitate extinction of mouse operant behaviour

Several recent studies have shown that reducing gamma-aminobutyric acid (GABA)-mediated neurotransmission retards extinction of aversive conditioning. However, relatively little is known about the effect of GABA on extinction of appetitively motivated tasks. We examined the effect of chlordiazepoxide (CDP), a classical benzodiazepine (BZ) and two novel subtype-selective BZs when administered to male C57Bl/6 mice during extinction following training on a discrete-trial fixed-ratio 5 (FR5) food reinforced lever-press procedure. Initially CDP had no effect, but after several extinction sessions CDP significantly facilitated extinction, i.e. slowed responding, compared with vehicle-treated mice. This effect was not due to drug accumulation because mice switched from vehicle treatment to CDP late in extinction showed facilitation immediately. Likewise, this effect could not be attributed to sedation because the dose of CDP used (15 mg/kg i.p.) did not suppress locomotor activity. The two novel subtype-selective BZ partial agonists, L-838417 and TP13, selectively facilitated extinction in similar fashion to CDP. The non-GABAergic anxiolytic buspirone was also tested and found to have similar effects when administered at a non-sedating dose. These studies demonstrate that GABA-mediated processes are important during extinction of an appetitively motivated task, but only after the animals have experienced several extinction sessions.

Behaviour models clarify definitions of affordance and capability

There is ongoing work on conceptual modelling of such busi- ness notions as Affordance and Capability. We have found that such business notions as Affordance and Capability are constructively defned using elements and properties of exe- cutable behaviour models. In this paper, we clarify the def- initions of Affordance and Capability using Coloured Petri Nets and Protocol models.The illustrating case is the process of drug injection. We show that different behaviour modelling techniques provide different precision for definition of Affordance and Capability and clarify the conceptual models of these notions. We generalise that the behaviour models can be used to improve the precision of conceptualization.

Workaround motivation model (WAMM): an adaptation of the Theory of Interpersonal Behaviour

The study of workarounds (WA) has increased in importance due to their impact on patient safety and efficiency. However, there are no adequate theories to explain the motivation to create and use a workaround in a healthcare sitting. Although theories of technology acceptance help to understand the reasons to accept or reject technology, they fail to explain drivers for alternatives. Also workarounds involve creators and performers that have different motivations. Models such as Theory of Planned Behaviour (TPB) or Theory of Reasoned Action (TRA) can help to explain the role of workaround users, but lack explanation of workaround creators’ dynamics. Our aim is to develop a theoretical foundation to explain workaround motivation behaviour models with norms that relate to sanctions to provide an integrated Workaround Motivation Model; WAMM. The development of WAMM model is explained in this paper based on workaround cases as part of further research to establish the model.

A DFT study of the structures, stabilities and redox behaviour of the major surfaces of magnetite Fe3O4

The renewed interest in magnetite (Fe3O4) as a major phase in different types of catalysts has led us to study the oxidation–reduction behaviour of its most prominent surfaces. We have employed computer modelling techniques based on the density functional theory to calculate the geometries and surface free energies of a number of surfaces at different compositions, including the stoichiometric plane, and those with a deficiency or excess of oxygen atoms. The most stable surfaces are the (001) and (111), leading to a cubic Fe3O4 crystal morphology with truncated corners under equilibrium conditions. The scanning tunnelling microscopy images of the different terminations of the (001) and (111) stoichiometric surfaces were calculated and compared with previous reports. Under reducing conditions, the creation of oxygen vacancies in the surface leads to the formation of reduced Fe species in the surface in the vicinity of the vacant oxygen. The (001) surface is slightly more prone to reduction than the (111), due to the higher stabilisation upon relaxation of the atoms around the oxygen vacancy, but molecular oxygen adsorbs preferentially at the (111) surface. In both oxidized surfaces, the oxygen atoms are located on bridge positions between two surface iron atoms, from which they attract electron density. The oxidised state is thermodynamically favourable with respect to the stoichiometric surfaces under ambient conditions, although not under the conditions when bulk Fe3O4 is thermodynamically stable with respect to Fe2O3. This finding is important in the interpretation of the catalytic properties of Fe3O4 due to the presence of oxidised species under experimental conditions.

Determinants of biosecurity behaviour of British cattle and sheep farmers: a behavioural economics analysis

The paper analyses the impact of a priori determinants of biosecurity behaviour of farmers in Great Britain. We use a dataset collected through a stratified telephone survey of 900 cattle and sheep farmers in Great Britain (400 in England and a further 250 in Wales and Scotland respectively) which took place between 25 March 2010 and 18 June 2010. The survey was stratified by farm type, farm size and region. To test the influence of a priori determinants on biosecurity behaviour we used a behavioural economics method, structural equation modelling (SEM) with observed and latent variables. SEM is a statistical technique for testing and estimating causal relationships amongst variables, some of which may be latent using a combination of statistical data and qualitative causal assumptions. Thirteen latent variables were identified and extracted, expressing the behaviour and the underlying determining factors. The variables were: experience, economic factors, organic certification of farm, membership in a cattle/sheep health scheme, perceived usefulness of biosecurity information sources, knowledge about biosecurity measures, perceived importance of specific biosecurity strategies, perceived effect (on farm business in the past five years) of welfare/health regulation, perceived effect of severe outbreaks of animal diseases, attitudes towards livestock biosecurity, attitudes towards animal welfare, influence on decision to apply biosecurity measures and biosecurity behaviour. The SEM model applied on the Great Britain sample has an adequate fit according to the measures of absolute, incremental and parsimonious fit. The results suggest that farmers’ perceived importance of specific biosecurity strategies, organic certification of farm, knowledge about biosecurity measures, attitudes towards animal welfare, perceived usefulness of biosecurity information sources, perceived effect on business during the past five years of severe outbreaks of animal diseases, membership in a cattle/sheep health scheme, attitudes towards livestock biosecurity, influence on decision to apply biosecurity measures, experience and economic factors are significantly influencing behaviour (overall explaining 64% of the variance in behaviour).

The mediating effect of environmental and ethical behaviour on supply chain partnership decisions and management appreciation of supplier partnership risks

Green supply chain management and environmental and ethical behaviour (EEB), a major component of corporate responsibility (CR), are rapidly developing fields in research and practice. The influence and effect of EEB at the functional level, however, is under-researched. Similarly, the management of risk in the supply chain has become a practical concern for many firms. It is important that managers have a good understanding of the risks associated with supplier partnerships. This paper examines the effect of firms’ investment in EEB as part of corporate social responsibility in mediating the relationship between supply chain partnership (SCP) and management appreciation of the risk of partnering. We hypothesise that simply entering into a SCP does not facilitate an appreciation of the risk of partnering and may even hamper such awareness. However, such an appreciation of the risk is facilitated through CR’s environmental and stakeholder management ethos. The study contributes further by separating risk into distinct relational and performance components. The results of a firm-level survey confirm the mediation effect, highlighting the value to supply chain strategy and design of investing in EEB on three fronts: building internal awareness, monitoring and sharing best practice.

Classification of seed storage behaviour of 67 Amazonian tree species

Information was collated on the seed storage behaviour of 67 tree species native to the Amazon rainforest of Brazil; 38 appeared to show orthodox, 23 recalcitrant and six intermediate seed storage behaviour. A double-criteria key based on thousand-seed weight and seed moisture content at shedding to estimate likely seed storage behaviour, developed previously, showed good agreement with the above classifications. The key can aid seed storage behaviour identification considerably.

Nightside studies of coherent HF Radar spectral width behaviour

A previous case study found a relationship between high spectral width measured by the CUTLASS Finland HF radar and elevated electron temperatures observed by the EISCAT and ESR incoherent scatter radars in the postmidnight sector of magnetic local time. This paper expands that work by briefly re-examining that interval and looking in depth at two further case studies. In all three cases a region of high HF spectral width (>200 ms−1) exists poleward of a region of low HF spectral width (<200 ms^{−1}). Each case, however, occurs under quite different geomagnetic conditions. The original case study occurred during an interval with no observed electrojet activity, the second study during a transition from quiet to active conditions with a clear band of ion frictional heating indicating the location of the flow reversal boundary, and the third during an isolated substorm. These case studies indicate that the relationship between elevated electron temperature and high HF radar spectral width appears on closed field lines after 03:00 magnetic local time (MLT) on the nightside. It is not clear whether the same relationship would hold on open field lines, since our analysis of this relationship is restricted in latitude. We find two important properties of high spectral width data on the nightside. Firstly the high spectral width values occur on both open and closed field lines, and secondly that the power spectra which exhibit high widths are both single-peak and multiple-peak. In general the regions of high spectral width (>200 ms−1) have more multiple-peak spectra than the regions of low spectral widths whilst still maintaining a majority of single-peak spectra. We also find that the region of ion frictional heating is collocated with many multiplepeak HF spectra. Several mechanisms for the generation of high spectral width have been proposed which would produce multiple-peak spectra, these are discussed in relation to the data presented here. Since the regions of high spectral width are observed both on closed and open field lines the use of the boundary between low and high spectral width as an ionospheric proxy for the open/closed field line boundary is not a simple matter, if indeed it is possible at all.

The Cognitive Behaviour Therapy Scale for Children and Young People (CBTS-CYP): development and psychometric properties

Background: There is increased interest in developing training in cognitive behaviour therapy (CBT) with children and young people. However, the assessment of clinical competence has relied upon the use of measures such as the Cognitive Therapy Scale-Revised (CTSR: Blackburn et al., 2001) which has been validated to assess competence with adults. The appropriateness of this measure to assess competence when working with children and young people has been questioned. Aim: This paper describes the development and initial evaluation of the Cognitive Behaviour Therapy Scale for Children and Young People (CBTSCYP) developed specifically to assess competence in CBT with children and young people. Method: A cross section of child CBT practitioners (n = 61) were consulted to establish face validity. Internal reliability, convergent validity and discriminative ability were assessed in two studies. In the first, 12 assessors independently rated a single video using both the Cognitive Behaviour Therapy Scale for Children and Young People (CBTS-CYP) and Cognitive Therapy Scale-Revised (CTS-Revised: Blackburn et al., 2001). In the second, 48 different recordings of CBT undertaken with children and young people were rated on both the CBTS-CYP and CTS-R. Results: Face validity and internal reliability of the CBTS-CYP were high, and convergent validity with the CTS-R was good. The CBTS-CYP compared well with the CTSR in discriminative ability. Conclusion: The CBTS-CYP provides an appropriate way of assessing competence in using CBT with children and young people. Further work is required to assess robustness with younger children and the impact of group training in reducing interrater variations.

Nuclear Factor-kappaB controls the reaggregation of 3D neurosphere cultures in vitro

The approach of reaggregation involves the regeneration and self-renewal of histotypical 3D spheres from isolated tissue kept in suspension culture. Reaggregated spheres can be used as tumour, genetic, biohybrid and neurosphere models. In addition the functional superiority of 3D aggregates over conventional 2D cultures developed the use of neurospheres for brain engineering of CNS diseases. Thus 3D aggregate cultures created enormous interest in mechanisms that regulate the formation of multicellular aggregates in vitro. Here we analyzed mechanisms guiding the development of 3D neurosphere cultures. Adult neural stem cells can be cultured as self-adherent clusters, called neurospheres. Neurospheres are characterised as heterogeneous clusters containing unequal stem cell sub-types. Tumour necrosis factor-alpha (TNF-alpha is one of the crucial inflammatory cytokines with multiple actions on several cell types. TNF-alpha strongly activates the canonical Nuclear Factor Kappa-B (NF- kappaB) pathway. In order to investigate further functions of TNF in neural stem cells (NSCs) we tested the hypothesis that TNF is able to modulate the motility and/or migratory behaviour of SVZ derived adult neural stem cells. We observed a significantly faster sphere formation in TNF treated cultures than in untreated controls. The very fast aggregation of isolated NSCs (<2h) is a commonly observed phenomenon, though the mechanisms of 3D neurosphere formation remain largely unclear. Here we demonstrate for the first time, increased aggregation and enhanced motility of isolated NSCs in response to the TNF-stimulus. Moreover, this phenomenon is largely dependent on activated transcription factor NF-kappaB. Both, the pharmacological blockade of NF-kappaB pathway by pyrrolidine dithiocarbamate (PDTC) or Bay11-7082 and genetic blockade by expression of a transdominant-negative super-repressor IkappaB-AA1 led to decreased aggregation.