mu O-conotoxin MrVIB selectively blocks Na(v)1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits

The tetroclotoxin-resistant voltage-gated sodium channel (VGSC) Na(v)1.8 is expressed predominantly by damage-sensing primary afferent nerves and is important for the development and maintenance of persistent pain states. Here we demonstrate that mu O-conotoxin MrVIB from Conus marmoreus displays substantial selectivity for Na(v)1.8 and inhibits pain behavior in models of persistent pain. In rat sensory neurons, submicromolar concentrations of MrVIB blocked tetroclotoxin-resistant current characteristic of Na(v)1.8 but not Na(v)1.9 or tetroclotoxin-sensitive VGSC currents. MrVIB blocked human Nav1.8 expressed in Xenopus oocytes with selectivity at least 10-fold greater than other VGSCs. In neuropathic and chronic inflammatory pain models, allodynia and hyperalgesia were both reduced by intrathecal infusion of MrVIB (0.03-3 nmol), whereas motor side effects occurred only at 30-fold higher doses. In contrast, the nonselective VGSC blocker lignocaine displayed no selectivity for allodynia and hyperalgesia versus motor side effects. The actions of MrVIB reveal that VGSC antagonists displaying selectivity toward Na(v)1.8 can alleviate chronic pain behavior with a greater therapeutic index than nonselective antagonists.

Direct inhibitory effects of an antisense oligodeoxynucleotide upon the volume-sensitive chloride current in rat osteoblast-like (ROS 17/2.8) cells

The effects of a 15-mer antisense c-myc phosphorothioate modified oligodeoxynucleotide (OdN) upon the volume-sensitive Cl- current in ROS 17/2.8 cells were investigated using the whole-cell configuration of the patch clamp technique. At 5 microM, the OdN reversibly inhibited the current in a voltage- and time-dependent fashion. This was evident from the reduction in the peak current as assessed at the termination of each voltage pulse and an acceleration of the time-dependent inactivation present at strongly depolarised potentials. The kinetic modifications induced by the OdN suggest it may act by blocking the pore of open channels when the cell membrane potential is depolarised.

Domestic violence and child abuse: developing sensitive policies

Domestic violence is everywhere and nowhere. No statutory organization or health service has work with either perpetrators or survivors of domestic violence (usually women and children) as the primary focus of their service, yet all agencies will have very significant numbers among their clients/service users. It is therefore crucial that the policy framework is developed both within and between agencies to address the need, and scope, of intervention in this area and particularly the impact on children. Currently, significant steps have been taken by some agencies in the UK to address this previously neglected issue, though the developments are patchy. This paper draws on a UK-wide research study which mapped the extent and range of service provision for families where there is domestic violence and also developed a framework of good practice indicators for ‘Mapped the extent and range of service provision for families where there is domestic violence and also developed a framework of good practice indicators’ provision in this area. This article examines one of the indicators of good practice arising from the research—that of policy development—within social service departments and within the multi-agency arena.

Studies in the marketing strategy of a U.K. producer of conveyor belts

Research was undertaken in the field of marketing strategy, its formulation and implementation in Dunlop Belting Division. Emphasis was placed on marketing channel strategy, but other strategies including product strategy were studied. The research has resulted in changes in management practice in the client organisation. The relevance of theories of company organisation, planning and strategy, and marketing channels was examined in the light of the research evidence. The technique of action-research was used to gain admittance to and effect change within the client organisation. Case study material was collected for subsequent analysis. The factors affecting marketing strategy formulation in the client organisation were studied. Both the external and the internal business environments were considered. The operation of the observed marketing channels was compared with channel theory. Market segmentation and penetration, and the selling and technical resources of the channels were analysed. Recommendations were made to (a) enlarge and resite the client's distribution unit to locate it centrally in England (b) use the resited unit to secure local advantage (c) obtain greater integration of field sales activities with and from the centre. A new ex-stock distribution unit was established. Improvements to the client's ex-stock marketing in Scotland were also recommended, including improvements to the Scottish distributor's stock control procedure, as well as to Dunlop-Distributor relationships at all levels. The influence of company organisation structure and formalised procedures and systems on the formulation of strategy were considered with respect to channel and product strategy, and other aspects of marketing. Conclusions were drawn that the action research resulted in successful implementation of .agreed changes in the client organisation; that theories of strategy formulation and planning, of the operation of decentralised companies, and of industrial market segmentation required modification; that the theory of marketing channels was found relevant and useful.

Highly radiation sensitive type IA FBGs for future dosimetry applications

We have studied Co60 gamma-irradiation effect on the characteristics of Type IA fiber Bragg gratings. A record Bragg peak shift of 190 pm was observed for a grating written in Fibercore PS-1250/1500 photosensitive fiber at a radiation dose of 116 kGy. Type IA and Type I gratings show different kinetics under radiation and during post-radiation annealing, which can be used for the design of a grating based dosimetry system.

A practical phase sensitive amplification scheme for two channel phase regeneration

A "black-box" phase sensitive amplifier is presented achieving simultaneous suppression of deterministic phase distortion on two independent 42.66 Gbit/s DPSK modulated signal wavelengths.

Phase synchronization scheme for a practical phase sensitive amplifier of ASK-NRZ signals

We present a phase locking scheme that enables the demonstration of a practical dual pump degenerate phase sensitive amplifier for 10 Gbit/s non-return to zero amplitude shift keying signals. The scheme makes use of cascaded Mach Zehnder modulators for creating the pump frequencies as well as of injection locking for extracting the signal carrier and synchronizing the local lasers. An in depth optimization study has been performed, based on measured error rate performance, and the main degradation factors have been identified.

Optimal packing for cascaded regenerative transmission based on phase sensitive amplifiers

We investigate the transmission performance of advanced modulation formats in nonlinear regenerative channels based on cascaded phase sensitive amplifiers. We identify the impact of amplitude and phase noise dynamics along the transmission line and show that after a cascade of regenerators, densely packed single ring PSK constellations outperform multi-ring constellations. The results of this study will greatly simplify the design of future nonlinear regenerative channels for ultra-high capacity transmission

Highly radiation sensitive type IA FBGs for future dosimetry applications

We have studied Co60 gamma-irradiation effect on the characteristics of Type IA fiber Bragg gratings. A record Bragg peak shift of 190 pm was observed for a grating written in Fibercore PS-1250/1500 photosensitive fiber at a radiation dose of 116 kGy. Type IA and Type I gratings show different kinetics under radiation and during post-radiation annealing, which can be used for the design of a grating based dosimetry system.

When do incentives work in channels of distribution?

The incentive dilemma refers to a situation in which incentives are offered but do not work as intended. The authors suggest that, in an interorganizational context, whether a principal-provided incentive works is a function of how it is evaluated by an agent: for its contribution to the agent's bottom line (instrumental evaluation) and for the extent it is strategically aligned with the agent's direction (congruence evaluation). To further understand when incentives work, the influence of two key contextual variables-industry volatility and dependence-are examined. A field study featuring 57 semi-structured depth interviews and 386 responses from twin surveys in the information technology and brewing industries provide data for hypothesis testing. When and whether incentives work is demonstrated by certain conditions under which the agent's evaluation of an incentive has positive or negative effects on its compliance and active representation. Further, some outcomes are reversed in the high volatility condition. © 2013 Academy of Marketing Science.