Search

A key capability of ion channels is the facilitation of selective permeation of certain ionic species across cellular membranes at high rates. Due to their physiological significance, ion channels are of great pharmaceutical interest as drug targets. The polymodal signal-detecting Transient Receptor Potential (TRP) superfamily of ion channels form a particularly promising group of drug targets. While most members of this family permeate a broad range of cations, TRPM4 and TRPM5 are unique due to their strong monovalent-selectivity and impermeability for divalent cations. Here, we address the mechanistic basis for their unique monovalent-selectivity. We present results fromin silicoelectrophysiology simulations of cation permeation through the TRPM5 channel, showing that monovalent cations permeate by a co-operative, distant knock-on mechanism between cation binding sites in the extracellular pore vestibule and the pore cavity. By contrast, divalent cations experience an energy barrier within the pore cavity, which inhibits their permeation via a knock-on mechanism.

This paper outlines the results of a two month study in which a series of extremist Islamist websites - registered, hosted or given datacentre services by Canadian internet companies- were empirically observed. The results of this project are inserted into a framework which explores the misuse and wrongful application of the "terrorist" signifier to substate or nonstate activities, discerns between the purported use of the internet by extremist Islamist organizations for destructive means and the real use of the internet by such groups, and suggests a number of conclusions based on prior administrative responses to the extremist Islamist use of the internet. The full results of this project can he viewed at http://www.stonnloader.com/metnbers/nordicfury.

The selective exchange of ions across cellular membranes is a vital biological process. Ca2+-mediated signalling is implicated in a broad array of physiological processes in cells, whilst elevated intracellular concentrations of Ca2+ are cytotoxic. Due to the significance of this cation, strict Ca2+ concentration gradients are maintained across the plasma and organelle membranes. Therefore, Ca2+ signalling relies on permeation through selective ion channels that control the flux of Ca2+ ions. A key family of Ca2+-permeable membrane channels are the polymodal signal-detecting Transient Receptor Potential (TRP) ion channels. TRP channels are activated by a wide variety of cues including temperature, small molecules, transmembrane voltage and mechanical stimuli. Whilst most members of this family permeate a broad range of cations non-selectively, TRPV5 and TRPV6 are unique due to their strong Ca2+-selectivity. Here, we address the question of how some members of the TRPV subfamily show a high degree of Ca2+-selectivity whilst others conduct a wider spectrum of cations. We present results from all-atom molecular dynamics simulations of ion permeation through two Ca2+-selective and two non-selective TRPV channels. Using a new method to quantify permeation co-operativity based on mutual information, we show that Ca2+-selective TRPV channel permeation occurs by a three binding site knock-on mechanism, whereas a two binding site knock-on mechanism is observed in non-selective TRPV channels. Each of the ion binding sites involved displayed greater affinity for Ca2+ over Na+. As such, our results suggest that coupling to an extra binding site in the Ca2+-selective TRPV channels underpins their increased selectivity for Ca2+ over Na+ ions. Furthermore, analysis of all available TRPV channel structures shows that the selectivity filter entrance region is wider for the non-selective TRPV channels, slightly destabilising ion binding at this site, which is likely to underlie mechanistic decoupling.

The influence of different thiophene donor units on electrochemical and spectroscopic properties of benzothiadiazole based donor–acceptor π-conjugated organic materials is studied. Two different structure modification vectors of the donor units are being considered – one addressing the intermolecular interactions through off-conjugation side chain architecture, and the other focusing on intramolecular interactions tuned by in-conjugation substituents. Electrochemical and simultaneous in situ EPR-UV-Vis-NIR spectroelectrochemical studies of the oxidative (p-) and reductive (n-) doping processes, which are responsible for the optoelectronic properties of these materials, revealed their disparate course and dissimilar effects of redox reactions of the conjugated π-bond. While p-doping prevalent species were found to comprise intensively interacting spin bearing and spinless charge carriers, the n-doping state was found to involve only one type of negatively charged carrier, with spin carrying species being selectively generated at due cathodic potentials. No spin pairing of these negative polarons was observed with their increasing population behaving like a collection of localised charge carriers. Qualitative and quantitative comparisons between the p- and n-doping carrier populations provided independent support for the spin pairing phenomena of positive charge carriers. Steric effects of varying alkyl side chain substitution have demonstrated predominant impact on the electrochemical properties of investigated polymers, and, thereto related, stability of n-doped state, while mesomeric effects of different 3,4-ethylenechalcogenide thiophene functionalities have been found to shape the energy level related spectral properties of these polymers, with particular reference to p-doping induced charged states. These findings provide new insights into the factors requiring attention during structure tailoring of donor–acceptor assemblies for organic optoelectronic applications.

Oligofluorene-functionalised truxenes containing perfluorohexylthiophene units at the terminal positions on the arms were synthesised, and their optical and electrochemical properties were investigated to determine the effect that the perfluorohexylthiophene unit has on the HOMO and LUMO properties of the oligomers. By synthesising a molecule with longer oligofluorene arms the effects of the perfluorohexylthiophene unit on larger oligomers was explored. The effect of steric hindrance from the perfluorohexyl chain was also evaluated by altering the position of the chain on the thiophene moiety.

With the increased and continuous threat of terrorist attacks in public areas, new sensors are required to safeguard the public from homemade explosive devices. Current commercial sensors for explosive vapors are high-cost, bulky equipment, not amenable to mass production, thus limiting their widespread deployment within society. We are conducting research on polymer-based microsensors that can overcome these limitations. Our devices offer an approach to the realization of low-cost sensors that can readily be placed as a network of electronic sentinels that can be permanently located in the areas of public access. The polymers are chemically tailored to have a high affinity for nitro and peroxide vapors and are grown electrochemically on microelectrodes. Novel nanoporous polymer-based sensors are demonstrated with a detection level of 200 ppb of nitro vapors. In addition, a prototype reversible sensor for peroxide vapors is demonstrated to low ppm concentrations.

Aim: The aim of this study was to explore childhood immunisations with a sample of parents from a population where children have high vaccination coverage and to identify factors which might encourage uptake in other populations. Methods: This research was conducted as part of a larger study on childhood immunisations in Hong Kong. In-depth interviews were conducted with a subsample of parents (n = 15) to further explore general perceptions and health beliefs about childhood immunisations. Interview data were analysed using content analysis techniques. Results: Three core themes emerged from the data: individual influences factors, family and social factors, and system factors. [Correction added after online publication 21/8/08: sentence corrected from “Four core themes emerged from the data: individual influences, family influences and system influences.”] Parents readily admitted knowledge deficits concerning childhood vaccines but believed that the benefits of immunisation outweighed the risks. Family members and peers were a source of pro-immunisation advice and comprehensive public health programmes and mandatory vaccination requirements for school entry ensured that childhood immunisation recommendations were followed. Conclusions: Overall, Hong Kong parents are highly supportive of immunisation programmes and insight gained from this study could prove helpful to providers trying to improve uptake rates among other populations.

In this paper a practical design procedure is suggested for designing wideband miniature interdigital filters. The proposed design approach is based on a concept of parameter mapping between two wideband filters, i.e. a conventional interdigital filter with uniform impedance resonators (UIR) and a desired miniature interdigital filter using stepped impedance resonators (SIR), allowing filter designers to deploy traditional designs with powerful electromagnetic (EM) simulators. For demonstration, a five-pole SIR interdigital filter with a fractional bandwidth (FBW) of 25% has been designed, fabricated, and tested. The demonstrator shows an excellent performance, which matches well to that of its conventional counterpart so as to validate the proposed design procedure. © 2006 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2007.

Current commercial sensors for explosive vapours are high cost bulky equipment not amenable to mass production and thus prevents their mass deployment within society. Our research objective is to create compact sensors that are not only portable but of such low cost that they can be installed in buildings in the same way as smoke detectors. We have developed novel polymers whose properties have been tailored to give them a higher affinity to target nitro group (NO2) bearing molecules associated with explosives. The polymers have been grown electrochemically onto miniature interdigitated electrode platforms yielding miniature sensors. Novel porous polymers based sensors are demonstrated which yield a detection level of 200 ppb of nitro vapours and can be manufactured at low-unit-cost.

Novel tetrathiafulvalene (TTF) containing compounds (III) are obtained by four-fold Stille coupling between tetrabromo-dithieno TTF (I) and stannylated thiophene (IIa) or thiazole (IIb).

Two novel tetrathiafulvalene (TTF) containing compounds 1 and 2 have been synthesised via a four-fold Stille coupling between a tetrabromo-dithienoTTF 5 and stannylated thiophene 6 or thiazole 4. The optical and electrochemical properties of compounds 1 and 2 have been measured by UV–vis spectroscopy and cyclic voltammetry and the results compared with density functional theory (DFT) calculations to confirm the observed properties. Organic field effect transistor (OFET) devices fabricated from 1 and 2 demonstrated that the substitution of thiophene units for thiazoles was found to increase the observed charge transport, which is attributed to induced planarity through S–N interactions of adjacent thiazole nitrogen atoms and TTF sulfur atoms and better packing in the bulk.

This article presents a microwave interdigital filter manufactured on high resistive silicon substrate. Two filter designs are referenced in this article; both filters are five pole interdigital filters with one using uniform impedance resonators and the other using stepped impedance resonators. The fabrication of the filters on silicon has been possible with the use of micromachining. This therefore enables filters to be manufactured with smaller footprints and gives rise to further development with micro-electro-mechanical systems technology. © 2006 Wiley Periodicals, Inc. Microwave Opt Technol Lett 48: 1862–1866, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.21810

We review the argument for and against keeping slack during the transformation of a plan-filling organization to a profit-seeking firm. Before the demise of the command economies, organizations in Central and Eastern European (CEE) countries were typified as being overstaffed, although the degree of overstuffing (slack) varied from country to country. This article reports on two small empirical studies in East Germany and Slovenia and examines the experiences of downsizing and its effects on the remaining staff. The findings, especially from East German companies, demonstrate the potentially corrosive effects of staff cutbacks on levels of information exchange and trust among surviving work-group members. Evidence from the Slovenian firms indicates that some degree of slack can have very positive consequences for information exchange and trust. In neither case did managers perceive and attempt to mobilize slack as a strategic resource. In the 1980s and early 1990s, a generation of mainly U.S. middle managers in large firms became acquainted with one side of the slack argument. They were downsized: labor costs were cut with the aim of rallying profits. Subsequent reports by surviving top managers indicate the process went too far so that now there are problems in reaching strategic goals. There are at least two reasons for this Neil Thomson is Professor of International Business Management at the Nuremberg University of Applied Sciences, Bahnhofstr. 87, 90402 Nuremberg, Germany (e-mail: Neil.Thomson@fh-nuernberg.de). Carla Millar is Dean of the Twente Business School, P.O. Box 217, 7500 AE Enschede, The Netherlands (e-mail: tsm@tsm.nl). An earlier version of this paper was presented at the Fifteenth EGOS Colloquium, 4-6 July 1 999, Warwick Business School. The authors wish to thank Rainhart Lang and Ed Clark for their constructive and helpful comments on earlier drafts.

Objective To estimate the incidence of sport-related sudden cardiac death due to ischaemic heart disease (IHD) in competitive young Aboriginal sportsmen. Setting Northern Territory (NT), 1982-1996. Design Retrospective case series with cases identified from Australian Bureau of Statistics cause-of-death listings and NT coronial autopsy records. Main outcome measures Circumstances and incidence of sport-related sudden cardiac deaths due to IHD; autopsy findings. Results Between 1982 and 1996, there were eight sudden cardiac deaths due to IHD and related to sporting activity among Aboriginal sportsmen aged 15-37 years in the NT. Six were associated with games of Australian (rules) football. All occurred in the Top End of the NT in the wet season, and all occurred after the first half, or within an hour of, a game. Four of the players had macrosopic myocardial abnormalities (hypertrophy or previous infarcts) on autopsy. The estimated incidence of IHD-related sudden cardiac death among Aboriginal Australian football players in the NT was 19-24 per 100,000 player-years, compared with 0.54 per 100,000 player-years among Australian rules footballers of similar ages in Victoria. Conclusions Incidence of sudden cardiac death attributable to underlying IHD was extremely high among young NT Aboriginal Australian footballers. Prevention will best be achieved by funding culturally appropriate long-term strategies to reduce the incidence of IHD. However, in the short-term, community-controlled programs with education of athletes, heat-stress reduction strategies, and cardiovascular screening should reduce the incidence of sudden cardiac death in sport.

A novel ultra wideband (UWB) bandpass filter is presented, using a compact coupled microstrip/coplanar waveguide (CPW) structure. The filter comprises of a single CPW quarter-wavelength resonator which is coupled to two microstrip open-circuited stubs on the other side of a common substrate. The two microstrip open-circuited stubs, which are about a quarter-wavelength long at the center frequency, can function as two resonators with associated coupling arrangement to the CPW. This forms a very compact three-pole filter. The proposed filter also exhibits a quasi-elliptic function response, with one finite-frequency transmission zero closer to each side of the passband. Thus, a high selectivity is achieved using a small number of resonators, which leads to low insertion loss and group delay across the passband. The performance is predicated using EM simulations and verified experimentally. The experimental filter shows a fractional bandwidth of 90% at a center frequency of 6.4GHz, with two observable transmission zeros (attenuation poles) at 1.95 and 10.36GHz, respectively. Furthermore, it has a very small size only amounting to 0.25 by 0.08 guided wavelength at the center frequency

This paper reviews the literature in the fields of learning, knowledge creation and storage in organisations and links the theories in these fields to mergers and acquisitions. Specifically, mergers and acquisitions (M&As) of East German ex-combines by western firms are examined from the viewpoint of does the dominant culture always win or is it possible for two-way learning? The answer to these questions seems to depend upon the mode of acquisition, the level of acculturation and on the length of time elapsed. These three factors and others are combined into a model to predict potential results of M&As. The theory section is supported by data collected from six western M&As in East Germany where a total of 36 in-depth, open ended interviews were held. Dem vorliegenden Artikel wird ein Literaturuberblick zum organisationalen Lernen sowie der Wissenserzeugung und -speicherung von Wissen in Organisationen vorangestellt. Die entsprechenden Theorien werden auf das Spezialthema dieser JEEMS-Ausgabe ubertragen. Es werden Ubernahmen von ostdeutschen Kombinaten durch westliche Unternehmen untersucht. Folgende Frage steht dabei im Mittelpunkt: Gewinnt immer die dominante Kultur oder ist auch ein wechselseitiges Lernen moglich? Die Art des Zukaufs, der wahrgenommene Grad der Akkulturation und die seit der Ubernahme vergangene Zeit scheinen hierauf Einflus zu haben. Es wird ein Arbeitsmodell entwickelt, um die moglichen Folgen von Unternehmenszusammenschlussen vorhersagen zu konnen. Aussagen aus 36 Interviews in sechs untersuchten ostdeutschen Betrieben bekraftigen die theoretischen Vorannahmen.

Background The use of ketamine and midazolam in physician-led prehospital care teams within the UK is well established. Although both agents are in use by paramedics within emergency medical systems in North America and Australasia, there is a paucity of data relating to administration by UK paramedics. Methods A panel of clinicians utilised a standardised data extraction form to review patient report forms for all cases where an Advanced Paramedic Practitioner (APP) administered ketamine or midazolam from 1st May to 30th September 2015. Reviewers assessed indications for and appropriateness of administration, and identification and management of adverse events. Results A total of 21 patients received ketamine for analgesia (n=20, 95%) or to facilitate rapid extrication (n=1, 5%). Pain scores were recorded in 18 patients (90%), the majority of whom experienced a reduction in pain post administration (n=17, 94%). No adverse events occurred following ketamine use. Midazolam was administered to a total of 80 cases. The most common indications for administration were maintenance of an advanced airway in patients with return of spontaneous circulation post cardiac arrest (n=37, 46%), management of acute behavioural disturbance (n=28, 35%) and prolonged seizures (n=15, 18%). Transient airway compromise occurred in 10% (n=8) of cases, all of which were managed appropriately. No other adverse events occurred. The administration of ketamine and midazolam was judged to be appropriate in all cases. Conclusions The use of ketamine and midazolam in the context of an urban APP service with high levels of additional education, procedural experience and selective targeting to emergency calls appears safe and effective. Further prospective studies are warranted to confirm these findings.

This chapter reviews amplitude modulation (AM) AFM in air and its applications to high-resolution imaging and interpretation of macromolecular complexes. We discuss single DNA molecular imaging and DNA-protein interactions, such as those with topoisomerases and RNA polymerase. We show how relative humidity can have a major influence on resolution and contrast and how it can also affect conformational switching of supercoiled DNA. Four regimes of AFM tip-sample interaction in air are defined and described, and relate to water perturbation and/or intermittent mechanical contact of the tip with either the molecular sample or the surface. Precise control and understanding of the AFM operational parameters is shown to allow the user to switch between these different regimes: an interpretation of the origins of topographical contrast is given for each regime. Perpetual water contact is shown to lead to a high-resolution mode of operation, which we term SASS (small amplitude small set-point) imaging, and which maximizes resolution while greatly decreasing tip and sample wear and any noise due to perturbation of the surface water. Thus, this chapter provides sufficient information to reliably control the AFM in the AM AFM mode of operation in order to image both heterogeneous samples and single macromolecules including complexes, with high resolution and with reproducibility. A brief introduction to AFM, its versatility and applications to biology is also given while providing references to key work and general reviews in the field.

A novel method for near-hermetic packaging of integrated UWB passive devices based on multilayer liquid crystal polymer technology is presented in this paper. The aim of this work is to develop a cheap, easy-to-manufacture procedure that can be used to enclose already designed devices without the need of any redesign, and works up to 20GHz. To achieve this, a coplanar waveguide-to-microstrip (CPW-MS) transition is designed to connect the enclosed device with the outer environment. This allows for the device to be PCB mounted as well as providing isolation. Two experiments are presented to validate this approach: an enclosed MS line, in order to measure the losses introduced by the packaging; and then a real ultra wideband (UWB) filter replacing the MS line using the same packaging. Simulated and measured results are provided in order to validate this approach.

OBJECTIVE: To assess the causes of death for people in police or prison custody in Australia, with particular attention to the differences between Aboriginal and non-Aboriginal deaths. DESIGN, SETTING AND PARTICIPANTS: Retrospective collection and analysis of data about deaths occurring in police or prison custody in Australia in the 10-year period 1980-1989. RESULTS: In the period 1980-1989, 527 deaths are known to have occurred in police or prison custody. About half these deaths were due to self-harmful behaviour, including hanging. The next most frequent causes of death were diseases of the circulatory system, injuries and diseases of the respiratory system. CONCLUSION: The high number of deaths in custody resulting from self-harmful behaviour has important implications for the criminal justice and corrections systems. Minimisation of the number of people held in police and prison custody is important in preventing such deaths. Close attention needs to be paid to ensuring the safety of lock-ups and prisons and to the screening of people likely to be at risk of death from self-harmful behaviour. Custodial authorities have a clear responsibility to provide quality preventive and clinical health services to all people in custody. Special attention needs to be directed to the specific health needs of Aborigines, many of whom are at much greater health risk than are non-Aborigines. Language: en

Emergency medical services in Zimbabwe are of a very variable standard, and exist in many forms: *Reasonably well-developed urban emergency medical services systems mixed with very poorly resourced and under-developed rural services. *Very high patient workloads, with severely ill medical patients and a large proportion of major trauma and multiple-casualty situations (public safety is given a low priority, and public transport is poorly regulated). *Long emergency response times and patient transport distances. *Somewhat under resourced and under developed emergency departments, with large numbers of critically ill acute patients, as well as many non-emergency/chronic patients who have no other access to appropriate health care. This paper provides a description of the development of ambulance services and acute health care in Zimbabwe, and outline the current demands on the system. Particular reference is made to the City of Harare Ambulance Service, which is considered to be the most developed of the local authority services.

In this paper, a practical approach is described for designing an interdigital filter with stepped impedance resonators (SIR) over a large fractional bandwidth (FBW). Interdigital filter is already a very compact design using quarter-wavelength resonators. The use of SIR reduces the overall footprint of a conventional interdigital filter.

Negative luminescent (NL) devices, which to an IR observer appear colder than they actually are, have a wide range of possible applications, including for use as thermal radiation shields in IR cameras, and as IR sources in gas sensing systems. For many of these applications a large area (>1cm 2 ) device is required, together with as large as possible apparent temperature range. However, under reverse bias significant currents are required to reduce the carrier concentrations to the levels needed for maximum possible absorption. These may lead to current heating of the device, which in turn reduces the apparent temperature range. We have therefore used a novel micromachining technique to fabricate integrated optical concentrators in InSb/InAlSb and HgCdTe NL devices. Smaller area diodes can then be used to achieve the same absorption (e.g. for InSb an area reduction of 16 is possible) and the required currents are thus reduced. To fabricate the concentrators parabolic resist masks are first produced, which are approximately 10 μm high and approximately 53 μm wide, by resist reflow at 120 degrees C. Inductively coupled plasma (ICP) etching is then used to alternately etch the resist mask and the semiconductor, with oxygen and methane/hydrogen respectively, producing concentrators with almost parabolic profiles. Currently, the concentrators are typically 30 μm high, with a top diameter of approximately 15 μm. Continuing optimization of the process to reach the theoretical limits of optical gain is described.

Corporate entrepreneurship can play a central role in the integration of mergers and acquisitions. This paper describes a study spanning seven years for six mergers and acquisitions that involved UK, US and Swedish acquisitions of East German firms. The authors used the respective strengths of corporate entrepreneurship to predict the likely success or failure of each M&A, with very accurate results when they revisited the companies in 2001. The authors draw further lessons from the study by linking corporate entrepreneurship to the learning organisation and providing practical lessons for managers.

IR detectors are normally cooled to 80K or below to obtain the highest, background limited performance. We present results for indium antimonide/indium aluminium antimonide and mercury cadmium telluride detectors grown by epitaxial processes in order to facilitate high performance with reduced cooling requirements. The epitaxial growth enables structures to be grown which offer precise control of carrier generation and current leakage mechanisms so that the maximum temperature can be achieve din a photodiode operated in a conventional manner, near zero bias. These types of structure offer even greater operating temperature when reverse biased to suppress non-radiative generation mechanisms. The epitaxial growth also has advantages for conventional, 80K operation, which are described.