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.

The appraisal and management of multi-storey dwelling blocks using large concrete panel systems

This exploratory study is concerned with the integrated appraisal of multi-storey dwelling blocks which incorporate large concrete panel systems (LPS). The first step was to look at U.K. multi-storey dwelling stock in general, and under the management of Birmingham City Council in particular. The information has been taken from the databases of three departments in the City of Birmingham, and rearranged in a new database using a suite of PC software called `PROXIMA' for clarity and analysis. One hundred of their stock were built large concrete panel system. Thirteen LPS blocks were chosen for the purpose of this study as case-studies depending mainly on the height and age factors of the block. A new integrated appraisal technique has been created for the LPS dwelling blocks, which takes into account the most physical and social factors affecting the condition and acceptability of these blocks. This appraisal technique is built up in a hierarchical form moving from the general approach to particular elements (a tree model). It comprises two main approaches; physical and social. In the physical approach, the building is viewed as a series of manageable elements and sub-elements to cover every single physical or environmental factor of the block, in which the condition of the block is analysed. A quality score system has been developed which depends mainly on the qualitative and quantitative conditions of each category in the appraisal tree model, and leads to physical ranking order of the study blocks. In the social appraisal approach, the residents' satisfaction and attitude toward their multi-storey dwelling block was analysed in relation to: a. biographical and housing related characteristics; and b. social, physical and environmental factors associated with this sort of dwelling, block and estate in general.The random sample consisted of 268 residents living in the 13 case study blocks. Data collected was analysed using frequency counts, percentages, means, standard deviations, Kendall's tue, r-correlation coefficients, t-test, analysis of variance (ANOVA) and multiple regression analysis. The analysis showed a marginally positive satisfaction and attitude towards living in the block. The five most significant factors associated with the residents' satisfaction and attitude in descending order were: the estate, in general; the service categories in the block, including heating system and lift services; vandalism; the neighbours; and the security system of the block. An important attribute of this method, is that it is relatively inexpensive to implement, especially when compared to alternatives adopted by some local authorities and the BRE. It is designed to save time, money and effort, to aid decision making, and to provide ranked priority to the multi-storey dwelling stock, in addition to many other advantages. A series of solution options to the problems of the block was sought for selection and testing before implementation. The traditional solutions have usually resulted in either demolition or costly physical maintenance and social improvement of the blocks. However, a new solution has now emerged, which is particularly suited to structurally sound units. The solution of `re-cycling' might incorporate the reuse of an entire block or part of it, by removing panels, slabs and so forth from the upper floors in order to reconstruct them as low-rise accommodations.

Selective functionalisation of Re6 cluster anionic units:from hexa-hydroxo [Re6Q8(OH)6]4− (Q = S, Se) to neutral trans-[Re6Q8L4L′2] hybrid building blocks

The reaction of [Re6Q8(OH)6]4- (Q = S, Se) with p-tertbutylpyridine (TBP) in water leads to neutral trans-[Re6Q8(TBP)4(OH)2] whose hydroxyl reactivity with carboxylic acid and TBP exchange reaction with functional pyridine have been investigated.

Stumbling Blocks in Empirical Legal Research: Case Study Research

This article examines the main assumptions and theoretical underpinnings of case study method in legal studies. It considers the importance of research design, including the crucial roles of the academic literature review, the research question and the use of rival theories to develop hypotheses and the practice of identifying the observable implications of those hypotheses. It considers the selection of data sources and modes of analysis to allow for valid analytical inferences to be drawn in respect of them. In doing so it considers, in brief, the importance of case study selection and variations such as single or multi case approaches. Finally it provides thoughts about the strengths and weaknesses associated with undertaking socio-legal and comparative legal research via a case study method, addressing frequent stumbling blocks encountered by legal researchers, as well as ways to militate them. It is written with those new to the method in mind.

Synthesis and characterization of electron deficient heterocycles as building blocks for electronic materials

This thesis describes the synthesis of a new electropolymerizable viologen derivative. A reasonably high-yielding route is reported, and a preliminary investigation of its polymerisation is described. The viologen and its precursors were examined by 1H NMR, MS, IR and elemental analysis. The energies of the band gap for the materials have been calculated using UV-vis spectroscopy, and cyclic voltammetry was also used to estimate the oxidation and the reduction potentials and to calculate the HOMO and LUMO energies. Theoretical calculations were performed using DFT. The attempted synthesis of a new flavin-functionalised phenanthroline derivative is described. Unfortunately, the protocol used failed to provide the desired compounds.

[Cadastral map of the blocks surrounding Washington Circle, Washington D.C.].

Cadastral map of area bounded by 24th, L. 22nd, and I streets N.W.

Regionalism as trading blocks, a comparative analysis of the legal structure of the EC and NAFTA within the context of the WTO

Geography has almost become obsolete. The world’s goods and services can now be accessed instantaneously by electronic commerce. Small and medium sized countries have felt the cold winds of change blowing, and have adopted the “safety in numbers” philosophy. Regional organisations throughout the world have sprung up, with their original raison d'être the encouragement and development of regional trading blocks. Two of the most developed regional groupings are the EU/EC and NAFTA. These two organisations represent two quite different philosophies of regional trade groupings, with contrasting legal structures. The advent of Trade Globalisation, with the founding of the WTO has brought these two approaches into confrontation, as each side of the Atlantic Ocean tries to influence the development on the naissant WTO. This paper examines the two contrasting legal structures, and the conflict on an inter regional level that they are engendering.

Mechanical properties of adobe blocks used in building construction in Huambo Province - Angola

Despite significant advances in building technologies with the use of conventional construction materials (as concrete and steel), which significantly have driven the construction industry, earth construction have demonstrated its importance and relevance, as well as it has matched in an efficient and eco-friendly manner the social housing concerns. The diversity of earth construction techniques allowed this material to adapt to different climatic, cultural and social contexts until the present time. However, in Angola, the construction with earth is still associated with population fringes of weak economic resources, for which, given the impossibility of being able to acquire modern construction materials (steel, cement, brick, among others), they resort to the use of available natural materials. Furthermore, the lack of scientific and technical knowledge justifies the negative appreciation of traditional building techniques, and the derogatory way how are considered the earth constructions in Angolan territory. Given the country's current development status, and taking into account the environmental requirements and the real socio-economic sustainability of Angola, it is considered that one of the viable and adequate options, could be the recovering and upgrading of the ancestral techniques of earth construction. The purpose of this research is to develop the technical and scientific knowledge in order to improve and optimize these construction solutions, responding to the real problems of housing quality as well as to the current social, economic and environmental sustainability requirements. In this paper, a description of the physical and mechanical characteristics of the adobes typically used in the construction of traditional houses in some localities of Huambo, province in Angola, is carried out. The methodology was based on mechanical in-situ testing in adobe blocks manufactured with traditional procedures: i) tensile strength evaluated with the bending test and compressive strength test on earth blocks specimens; and, ii) durability and erodibility test by Geelong method adopting the New Zealand standard (NZS) procedures (4297: 1998; 4297: 1998 and 4297: 1999). The results allow the characterization of the materials used in the construction of raw earth in the Huambo region, contributing to the development of knowledge of these sustainable and traditional housing constructive solutions with a strong presence in Angola [1, 2]. This study is part of a larger project in the area of Earth Construction [3], which aims to produce knowledge which can stimulate the use of environmental friendly construction materials and contribute to develop constructive solutions with improved performance, durability, comfort, safety and sustainability.

Causes of injuries resulting in hospitalisation in Australia : assessing coder agreement on external causes

Objective: To assess extent of coder agreement for external causes of injury using ICD-10-AM for injury-related hospitalisations in Australian public hospitals. Methods: A random sample of 4850 discharges from 2002 to 2004 was obtained from a stratified random sample of 50 hospitals across four states in Australia. On-site medical record reviews were conducted and external cause codes were assigned blinded to the original coded data. Code agreement levels were grouped into the following agreement categories: block level, 3-character level, 4-character level, 5th-character level, and complete code level. Results: At a broad block level, code agreement was found in over 90% of cases for most mechanisms (eg, transport, fall). Percentage disagreement was 26.0% at the 3-character level; agreement for the complete external cause code was 67.6%. For activity codes, the percentage of disagreement at the 3-character level was 7.3% and agreement for the complete activity code was 68.0%. For place of occurrence codes, the percentage of disagreement at the 4-character level was 22.0%; agreement for the complete place code was 75.4%. Conclusions: With 68% agreement for complete codes and 74% agreement for 3-character codes, as well as variability in agreement levels across different code blocks, place and activity codes, researchers need to be aware of the reliability of their specific data of interest when they wish to undertake trend analyses or case selection for specific causes of interest.