Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability

Epilepsy is the most common neurological disorder, with over 50 million people worldwide affected. Recent evidence suggests that the transient receptor potential cation channel subfamily V member 1 (TRPV1) may contribute to the onset and progression of some forms of epilepsy. Since the two nonpsychotropic cannabinoids cannabidivarin (CBDV) and cannabidiol (CBD) exert anticonvulsant activity in vivo and produce TRPV1-mediated intracellular calcium elevation in vitro, we evaluated the effects of these two compounds on TRPV1 channel activation and desensitization and in an in vitro model of epileptiform activity. Patch clamp analysis in transfected HEK293 cells demonstrated that CBD and CBDV dose-dependently activate and rapidly desensitize TRPV1, as well as TRP channels of subfamily V type 2 (TRPV2) and subfamily A type 1 (TRPA1). TRPV1 and TRPV2 transcripts were shown to be expressed in rat hippocampal tissue. When tested on epileptiform neuronal spike activity in hippocampal brain slices exposed to a Mg2+-free solution using multielectrode arrays (MEAs), CBDV reduced both epileptiform burst amplitude and duration. The prototypical TRPV1 agonist, capsaicin, produced similar, although not identical effects. Capsaicin, but not CBDV, effects on burst amplitude were reversed by IRTX, a selective TRPV1 antagonist. These data suggest that CBDV antiepileptiform effects in the Mg2+-free model are not uniquely mediated via activation of TRPV1. However, TRPV1 was strongly phosphorylated (and hence likely sensitized) in Mg2+-free solution-treated hippocampal tissue, and both capsaicin and CBDV caused TRPV1 dephosphorylation, consistent with TRPV1 desensitization. We propose that CBDV effects on TRP channels should be studied further in different in vitro and in vivo models of epilepsy.

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.

Transient atmospheric response to interactive SST anomalies

The transient atmospheric response to interactive SST anomalies in the midlatitudes is investigated using a three-layer QG model coupled in perpetual winter conditions to a slab oceanic mixed layer in the North Atlantic. The SST anomalies are diagnosed from a coupled run and prescribed as initial conditions, but are free to evolve. The initial evolution of the atmospheric response is similar to that obtained with a prescribed SST anomaly, starting as a quasi-linear baroclinic and then quickly evolving into a growing equivalent barotropic one. Because of the heat flux damping, the SST anomaly amplitude slowly decreases, albeit with little change in pattern. Correspondingly, the atmospheric response only increases until it reaches a maximum amplitude after about 1–3.5 months, depending on the SST anomaly considered. The response is similar to that at equilibrium in the fixed SST case, but it is 1.5–2 times smaller, and then slowly decays away.

Ring-opening polymerization in molten PEEK: transient reduction of melt-viscosity by macrocyclic aromatic thioetherketones

Blends of PEEK with macrocyclic thioether-ketones show initial melt-viscosities reduced by more than an order of magnitude relative to the polymer itself, enabling more facile processing and fabrication. On raising the temperature of the melt, however, the macrocycle undergoes spontaneous, entropically-driven ring-opening polymerization (ED-ROP), so that the properties of the final polymer should not, in principle, be compromised by the presence of low-MW macrocyclic material.

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.

Fractional order and non-linear system identification algorithms for biomedical applications

We discuss the modelling of dielectric responses of amorphous biological samples. Such samples are commonly encountered in impedance spectroscopy studies as well as in UV, IR, optical and THz transient spectroscopy experiments and in pump-probe studies. In many occasions, the samples may display quenched absorption bands. A systems identification framework may be developed to provide parsimonious representations of such responses. To achieve this, it is appropriate to augment the standard models found in the identification literature to incorporate fractional order dynamics. Extensions of models using the forward shift operator, state space models as well as their non-linear Hammerstein-Wiener counterpart models are highlighted. We also discuss the need to extend the theory of electromagnetically excited networks which can account for fractional order behaviour in the non-linear regime by incorporating nonlinear elements to account for the observed non-linearities. The proposed approach leads to the development of a range of new chemometrics tools for biomedical data analysis and classification.

Study of picosecond processes of an intercalated dipyridophenazine Cr(iii) complex bound to defined sequence DNAs using transient absorption and time-resolved infrared methods

Picosecond transient absorption (TA) and time-resolved infrared (TRIR) measurements of rac-[Cr(phen)2(dppz)]3+ (1) intercalated into double-stranded guanine-containing DNA reveal that the excited state is very rapidly quenched. As no evidence was found for the transient electron transfer products, it is proposed that the back electron transfer reaction must be even faster (<3 ps).

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.

Ground-based observations of the auroral zone and polar cap ionospheric responses to dayside transient reconnection

Observations from the EISCAT VHF incoherent scatter radar system in northern Norway, during a run of the common programme CP-4, reveal a series of polewardpropagating F-region electron density enhancements in the pre-noon sector on 23 November 1999. These plasma density features, which are observed under conditions of a strongly southward interplanetary magnetic field, exhibit a recurrence rate of under 10 min and appear to emanate from the vicinity of the open/closed field-line boundary from where they travel into the polar cap; this is suggestive of their being an ionospheric response to transient reconnection at the dayside magnetopause (flux transfer events). Simultaneous with the density structures detected by the VHF radar, polewardmoving radar auroral forms (PMRAFs) are observed by the Finland HF coherent scatter radar. It is thought that PMRAFs, which are commonly observed near local noon by HF radars, are also related to flux transfer events, although the specific mechanism for the generation of the field-aligned irregularities within such features is not well understood. The HF observations suggest, that for much of their existence, the PMRAFs trace fossil signatures of transient reconnection rather than revealing the footprint of active reconnection itself; this is evidenced not least by the fact that the PMRAFs become narrower in spectral width as they evolve away from the region of more classical, broad cusp scatter in which they originate. Interpretation of the HF observations with reference to the plasma parameters diagnosed by the incoherent scatter radar suggests that as the PMRAFs migrate away from the reconnection site and across the polar cap, entrained in the ambient antisunward flow, the irregularities therein are generated by the presence of gradients in the electron density, with these gradients having been formed through structuring of the ionosphere in the cusp region in response to transient reconnection.

Coordinated ground-based, low altitude satellite and Cluster observations on global and local scales during a transient post-noon sector excursion of the magnetospheric cusp

On 14 January 2001, the four Cluster spacecraft passed through the northern magnetospheric mantle in close conjunction to the EISCAT Svalbard Radar (ESR) and approached the post-noon dayside magnetopause over Greenland between 13:00 and 14:00 UT During that interval, a sudden reorganisation of the high-latitude dayside convection pattern accurred after 13:20 UT most likely caused by a direction change of the Solar wind magnetic field. The result was an eastward and poleward directed flow-channel, as monitored by the SuperDARN radar network and also by arrays of ground-based magnetometers in Canada, Greenland and Scandinavia. After an initial eastward and later poleward expansion of the flow-channel between 13:20 and 13:40 UT, the four Cluster spacecraft, and the field line footprints covered by the eastward looking scan cycle of the Sondre Stromfjord incoherent scatter radar were engulfed by cusp-like precipitation with transient magnetic and electric field signatures. In addition, the EISCAT Svalbard Radar detected strong transient effects of the convection reorganisation, a poleward moving precipitation, and a fast ion flow-channel in association with the auroral structures that suddenly formed to the west and north of the radar. From a detailed analysis of the coordinated Cluster and ground-based data, it was found that this extraordinary transient convection pattern, indeed, had moved the cusp precipitation from its former pre-noon position into the late post-noon sector, allowing for the first and quite unexpected encounter of the cusp by the Cluster spacecraft. Our findings illustrate the large amplitude of cusp dynamics even in response to moderate solar wind forcing. The global ground-based data proves to be an invaluable tool to monitor the dynamics and width of the affected magnetospheric regions.