Investigation of the effects of the novel anticonvulsant compound carisbamate(RWJ-333369) on rat piriform cortical neurones in vitro

Background and purpose: Carisbamate is being developed for adjuvant treatment of partial onset epilepsy. Carisbamate produces anticonvulsant effects in primary generalized, complex partial and absence-type seizure models, and exhibits neuroprotective and antiepileptogenic properties in rodent epilepsy models. Phase IIb clinical trials of carisbamate demonstrated efficacy against partial onset seizures; however, its mechanisms of action remain unknown. Here, we report the effects of carisbamate on membrane properties, evoked and spontaneous synaptic transmission and induced epileptiform discharges in layer II-III neurones in piriform cortical brain slices. Experimental approach: Effects of carisbamate were investigated in rat piriform cortical neurones by using intracellular electrophysiological recordings. Key results: Carisbamate (50–400 mmol·L-1) reversibly decreased amplitude, duration and rise-time of evoked action potentials and inhibited repetitive firing, consistent with use-dependent Na+ channel block; 150–400 mmol·L-1 carisbamate reduced neuronal input resistance, without altering membrane potential. After microelectrode intracellular Cl- loading, carisbamate depolarized cells, an effect reversed by picrotoxin. Carisbamate (100–400 mmol·L-1) also selectively depressed lateral olfactory tract-afferent evoked excitatory synaptic transmission (opposed by picrotoxin), consistent with activation of a presynaptic Cl conductance. Lidocaine (40–320 mmol·L-1) mimicked carisbamate, implying similar modes of action. Carisbamate (300–600 mmol·L-1) had no effect on spontaneous GABAA miniature inhibitory postsynaptic currents and at lower concentrations (50–200 mmol·L-1) inhibited Mg2+-free or 4-aminopyridine-induced seizure-like discharges. Conclusions and implications: Carisbamate blocked evoked action potentials use-dependently, consistent with a primary action on Na+ channels and increased Cl- conductances presynaptically and, under certain conditions, postsynaptically to selectively depress excitatory neurotransmission in piriform cortical layer Ia-afferent terminals.

Determination of the optical properties of plastic films used as cladding materials in novel energy efficient greenhouses

Greenhouse cladding materials are a major component in the design of energy efficient greenhouses. The optical properties of cladding materials determine a major part of the overall performance of a greenhouse both in terms of the energy balance of the greenhouse and on crop behavior. Various film plastic greenhouse-cladding materials were measured under laboratory conditions using a spectroradiometer equipped with an integrating sphere. Films were measured over a range of angles of incidence and the effect of increasing distance between double films was also measured. PAR transmission remained nearly constant for angles of incidence increased up to 30 degrees but fell rapidly thereafter as the angles of incidence increased up to 90 degrees. Increasing distance between double films did not significantly affect PAR transmission in all films examined. These results are discussed in relation to the design criteria for an energy efficient greenhouse.

Growth, yield and development of strawberry cv. 'Elsanta' under novel photoselective film clad greenhouses

Film greenhouse claddings are typically used to protect horticultural crops from low temperature and high rainfall conditions. However, a range of novel plastic films have been developed which filter specific radiation wavelengths with the aim of providing the grower with greater control of crop growth and development. A replicated experiment was conducted in 8 small experimental greenhouses, covered with different photoselective films characterised by a range of red/far-red ratios and PAR transmissions to study their effects on the growth, yield and quality of the strawberry cv. 'Elsanta'. Marketable yield per plant was 51% greater under the film with the highest light transmission (control) compared with the lower light transmission films. Similarly, unmarketable fruit number and average non-marketable individual fruit weight per plant was lowest under films with higher light transmissions and higher under lower light transmission films. Cropping duration was longer under films with high R/FR. Also plants under high R/FR were more compact (due to shorter petiole lengths) compared to plants grown under low R/FR. The results are discussed in relation to the increased use of photoselective films in protected horticulture and the need for higher quality fruit and vegetables.

A novel self-healing supramolecular polymer system

Utilising supramolecular pi-pi stacking interactions to drive miscibility in two-component polymer blends offers a novel approach to producing materials with unique properties. We report in this paper the preparation of a supramolecular polymer network that exploits this principle. A low molecular weight polydiimide which contains multiple pi-electron-poor receptor sites along its backbone forms homogeneous films with a siloxane polymer that features pi-electron-rich pyrenyl end-groups. Compatibility results from a complexation process that involves chain-folding of the polydiimide to create an optimum binding site for the pi-electron-rich chain ends of the polysiloxane. These complementary pi-electron-rich and -poor receptors exhibit rapid and reversible complexation behaviour in solution, and healable characteristics in the solid state in response to temperature. A mechanism is proposed for this thermoreversible healing behaviour that involves disruption of the intermolecular pi-pi stacking cross-links as the temperature of the supramolecular film is increased. The low T-g siloxane component can then flow and as the temperature of the blend is decreased, pi-pi stacking interactions drive formation of a new network and so lead to good damage-recovery characteristics of the two-component blend.

Synthesis of chiral 3,4,5,6-tetrahydro-1,4-thiazin-2-ones (thiamorpholin-2-ones)-novel heterocycles possessing enhanced carbonyl electrophilicity over their oxygen counterparts

We report herein the first synthesis of chiral derivatives possessing the 1,4-thiazinone core. As predicted, the thiolactone is more susceptible to nucleophilic attack than the equivalent lactone system.

A novel spectral representation of electromyographic signals

Time/frequency and temporal analyses have been widely used in biomedical signal processing. These methods represent important characteristics of a signal in both time and frequency domain. In this way, essential features of the signal can be viewed and analysed in order to understand or model the physiological system. Historically, Fourier spectral analyses have provided a general method for examining the global energy/frequency distributions. However, an assumption inherent to these methods is the stationarity of the signal. As a result, Fourier methods are not generally an appropriate approach in the investigation of signals with transient components. This work presents the application of a new signal processing technique, empirical mode decomposition and the Hilbert spectrum, in the analysis of electromyographic signals. The results show that this method may provide not only an increase in the spectral resolution but also an insight into the underlying process of the muscle contraction.

A novel soft decision QAM demodulator for DVB-T for multipath system

In 1997, the United Kingdom started the world's first commercial digital terrestrial television service. The system used was the European Digital Video Broadcast - Terrestrial (DVB-T) but due to technological constraints at the time, the system chosen was the 2K system - a system that uses 1705 carriers to convey the digital television services through a hostile terrestrial environment. Today, these constraints are no longer applicable but in order to maintain backwards compatibility to the older set top boxes, the 2K system is still used. The 2K system has the disadvantage of excluding the possibiliiy of employing a Single Frequency Network (SFN) - something that can help minimise the required bandwidth for television services. This paper will demonstrate a computationally inexpensive soft decision Quadrature Amplitude Modulation technique that can reject the multipaths. (1).

Novel actuator design to overcome stiction and backlash for low-velocity applications

This paper presents a novel actuator design that ameliorates or eliminates the effects of non-linearities that are characteristically present in geared actuator systems and which are very problematic for low velocity applications. The design centres on the providing an internal rotational element within a single actuator to ensure operation of actuator away from the stiction region, whilst allowing zero velocity external output of the actuator. The construction has the added advantage of substantially reducing backlash. The prototype comprises two commercially available servo-actuators to test the principle of operation and results presented indicate that the concept is worth exploring further.

Investigating novel point-select techniques for older people

As the number and proportion of older people worldwide continues to grow, robotic devices can play a role in helping older people continue to live independent and active lives. Graphical user interfaces (GUIs) and interactions that involve pointing to items and selecting them are becoming more common in assistive robots. The authors are currently working on a project investigating techniques to improve point-select interactions for older people. In particular, the project studies how older people respond to expanding and moving targets. The research is ongoing, and this paper describes the methods that will be used in upcoming experiments.

A novel two pass hexagonal search algorithm for motion estimation

This paper presents a novel two-pass algorithm constituted by Linear Hashtable Motion Estimation Algorithm (LHMEA) and Hexagonal Search (HEXBS). compensation. for block base motion On the basis of research from previous algorithms, especially an on-the-edge motion estimation algorithm called hexagonal search (HEXBS), we propose the LHMEA and the Two-Pass Algorithm (TPA). We introduce hashtable into video compression. In this paper we employ LHMEA for the first-pass search in all the Macroblocks (MB) in the picture. Motion Vectors (MV) are then generated from the first-pass and are used as predictors for second-pass HEXBS motion estimation, which only searches a small number of MBs. The evaluation of the algorithm considers the three important metrics being time, compression rate and PSNR. The performance of the algorithm is evaluated by using standard video sequences and the results are compared to current algorithms. Experimental results show that the proposed algorithm can offer the same compression rate as the Full Search. LHMEA with TPA has significant improvement on HEXBS and shows a direction for improving other fast motion estimation algorithms, for example Diamond Search.

MARCKS functions as a novel growth/tumour suppressor in cells of melanocyte origin

Protein kinase C (PKC) plays a pivotal role in modulating the growth of melanocytic cells in culture. We have shown previously that a major physiological substrate of PKC, the 80 kDa myristoylated alanine-rich C-kinase substrate (MARCKS), can be phosphorylated in quiescent, non-tumorigenic melanocytes exposed transiently to a biologically active phorbol ester, but cannot be phosphorylated in phorbol ester-treated, syngeneic malignant melanoma cells. Despite its ubiquitous distribution, the function of MARCKS in cell growth and transformation remains to be demonstrated clearly. We report here that MARCKS mRNA and protein levels are down-regulated significantly in the spontaneously derived murine B16 melanoma cell line compared with syngeneic normal Mel-ab melanocytes. In contrast, the tumourigenic v-Ha-ras-transfonned melan-ocytic line, LTR Ras 2, showed a high basal level of MARCKS phosphorylation which was not enhanced by treatment of cells with phorbol ester. Furthermore, protein levels of MARCKS in LTR Ras 2 cells were similar to those expressed in Mel-ab melanocytes. However, in four out of six murine tumour cell lines investigated, levels of MARCKS protein were barely detectable. Transfection of B16 cells with a plasmid containing the MARCKS cDNA in the sense orientation produced two neomycin-resistant clones displaying reduced proliferative capacity and decreased anchorage-independent growth compared with control cells. In contrast, transfection with the antisense MARCKS construct produced many colonies which displayed enhanced growth and transforming potential compared with control cells. Thus, MARCKS appears to act as a novel growth suppressor in the spontaneous transformation of cells of melanocyte origin and may play a more general role in the tumour progression of other carcinomas.