Structure-function studies of the plant cyclotides: The role of a circular protein backbone

The traditional idea of proteins as linear chains of amino acids is being challenged with the discovery of miniproteins that contain a circular backbone. The cyclotide family is the largest group of circular proteins and is characterized by an amide-circularized protein backbone and six conserved cysteine residues. These conserved cysteines are paired to form a knotted network of disulfide bonds. The combination of the circular backbone and a cystine knot, known as the cyclic cystine knot (CCK) motif, confers exceptional stability upon the cyclotides. This review discusses the role of the circular backbone based on studies of both the oxidative folding of kalata B1, the prototypical cyclotide, and a comparison of the structure and activity of kalata B1 and its acyclic permutants.

Chronic inflammatory demyelinating polyneuropathy and respiratory failure

Neuromuscular respiratory failure is not considered to be a clinical feature of chronic inflammatory demyelinating polyneuropathy (CIDP). We present 4 patients with CIDP who required respiratory assistance and mechanical ventilation. Two patients needed emergent intubation and one patient lapsed in a stupor from hypercapnia. Respiratory failure in CIDP should be considered exceptional, but more formal studies in CIDP may be needed to assess its prevalence.

Characterization of the highly efficient sucrose isomerase from Pantoea dispersa UQ68J and cloning of the sucrose isomerase gene

Sucrose isomerase (SI) genes from Pantoea dispersa UQ68J, Klebsiella planticola UQ14S, and Erwinia rhapontici WAC2928 were cloned and expressed in Escherichia coli. The predicted products of the UQ14S and WAC2928 genes were similar to known SIs. The UQ68J SI differed substantially, and it showed the highest isomaltulose-producing efficiency in E. coli cells. The purified recombinant WAC2928 SI was unstable, whereas purified UQ68J and UQ14S SIs were very stable. UQ68J SI activity was optimal at pH 5 and 30 to 35 degrees C, and it produced a high ratio of isomaltulose to trehalulose (> 22:1) across its pH and temperature ranges for activity (pH 4 to 7 and 20 to 50 degrees C). In contrast, UQ14S SI showed optimal activity at pH 6 and 35 degrees C and produced a lower ratio of isomaltulose to trehalulose (< 8:1) across its pH and temperature ranges for activity. UQ68J SI had much higher catalytic efficiency; the K-m was 39.9 mM, the V-max was 638 U mg(-1), and the K-cat/K-m was 1.79 x 104 M-1 s(-1), compared to a K-m of 76.0 mM, a V-max. of 423 U mg(-1), and a K-cat/K-m of 0.62 x 104 M-1 s(-1) for UQ14S SI. UQ68J SI also showed no apparent reverse reaction producing glucose, fructose, or trehalulose from isomaltulose. These properties of the P. dispersa UQ68J enzyme are exceptional among purified SIs, and they indicate likely differences in the mechanism at the enzyme active site. They may favor the production of isomaltulose as an inhibitor of competing microbes in high-sucrose environments, and they are likely to be highly beneficial for industrial production of isomaltulose.

Myths and plain truths about schizophrenia epidemiology - the NAPE lecture 2004

Objective: Science needs to constantly match research models against the data. With respect to the epidemiology of schizophrenia, the widely held belief that the incidence of schizophrenia shows little variation may no longer be supported by the data. The aims of this paper are (i) to explore data-vs.-belief mismatch with respect to the incidence of schizophrenia, and (ii) to speculate on the causes and consequences of such discrepancies. Method: Based on a recently published systematic review of the incidence of schizophrenia, the distribution of incidence rates around the world was examined. In order to examine if the incidence of schizophrenia differed by sex, male vs. female risk ratios were generated. Results: The distribution of incidence rates for schizophrenia is asymmetrical with many high rates skewing the distribution. Based on the central 80% of rates, the incidence of schizophrenia varies in a five-fold range (between 7.7 and 43.0 per 100 000). Males have a significantly higher incidence of schizophrenia compared with females (median male to female risk ratio = 1.4), and this difference could not be accounted for by diagnostic criteria or age range. Conclusion: The beliefs that (i) the incidence of schizophrenia does not vary between sites and (ii) males and females are equally affected, may have persisted because of an unspoken deeper belief that schizophrenia is an egalitarian and exceptional disorder. Our ability to generate productive hypotheses about the aetiology of schizophrenia rests on an accurate appraisal of the data. Beliefs not supported by data should be identified and relabelled as myths.

The Thelastomatoidea (Nematoda : Oxyurida) of two sympatric Panesthiinae (Insecta : Blattodea) from southeastern Queensland, Australia: taxonomy, species richness and host specificity

The thelastomatoid fauna of two species of wood-burrowing cockroach (Blattodea, Blaberidae), Panesthia cribrata and Panesthia tryoni tryoni, from Lamington National Park, Australia, is described. The following eight new species and three new genera of thelastomatid are proposed: Bilobostoma exerovulva n. g., n. sp.; Cordonicola gibsoni n. sp.; Coronostoma australiae n. sp.; Desmicola ornata n. sp.; Hammerschmidtiella hochi n. sp.; Malaspinanema goateri n. g., n. sp.; Travassosinema jaidenae n. sp.; and Tsuganema cribratum n. g., n. sp. Additional data are given for Blattophila sphaerolaima and Leidynemella fusiformis. Of the 11 species reported, nine were found in P. cribrata and ten in P. tryoni tryoni. Such levels of thelastomatoid species richnessness in single host species are exceptional. Only the mole cricket, Gryllotalpa africana (23), and the domestic cockroach, Periplaneta americana (20), have higher reported richness. Three species, T jaidenae, C. australiae and D. ornata, were found either exclusively or significantly more prevalently in P tryoni tryoni than in R cribrata. Species of Travassosinema, Coronostoma and Desmicola have been found previously only in millipedes (Diplopoda), a fact that suggests that there is a greater degree of niche overlap between R tryoni tryoni and millipedes than for R cribrata.

Eutectic grain size and strontium concentration in hypoeutectic aluminium-silicon alloys

Recently it has been shown that modification with strontium causes an increase in the size of eutectic grains. The eutectic grain size increases because there are fewer nucleation events, possibly due to the poisoning of phosphorus-based nuclei that are active in the unmodified alloy. The current paper investigates the effect of strontium concentration on the eutectic grain size. In the aluminium-10 wt.% silicon alloy used in this research, for fixed casting conditions, the eutectic grain size increases as the strontium concentration increases up to approximately 150ppm, beyond which the grain size is relatively stable. This critical strontium concentration is likely to differ depending on the composition of the base alloy, including the concentration of minor elements and impurities. It is concluded that processing and in-service properties of strontium modified aluminium-silicon castings are likely to be more stable if a minimum critical strontium concentration is exceeded. If operating below this critical strontium concentration exceptional control over composition and casting conditions is required. (c) 2005 Elsevier B.V. All rights reserved.

A novel suite of cyclotides from Viola odorata: sequence variation and the implications for structure, function and stability

Cyclotides are a fascinating family of plant-derived peptides characterized by their head-to-tail cyclized backbone and knotted arrangement of three disulfide bonds. This conserved structural architecture, termed the CCK (cyclic cystine knot), is responsible for their exceptional resistance to thermal, chemical and enzymatic degradation. Cyclotides have a variety of biological activities, but their insecticidal activities suggest that their primary function is in plant defence. In the present study, we determined the cyclotide content of the sweet violet Viola odorata, a member of the Violaceae family. We identified 30 cyclotides from the aerial parts and roots of this plant, 13 of which are novel sequences. The new sequences provide information about the natural diversity of cyclotides and the role of particular residues in defining structure and function. As many of the biological activities of cyclotides appear to be associated with membrane interactions, we used haemolytic activity as a marker of bioactivity for a selection of the new cyclotides. The new cyclotides were tested for their ability to resist proteolysis by a range of enzymes and, in common with other cyclotides, were completely resistant to trypsin, pepsin and thermolysin. The results show that while biological activity varies with the sequence, the proteolytic stability of the framework does not, and appears to be an inherent feature of the cyclotide framework. The structure of one of the new cyclotides, cycloviolacin O14, was determined and shown to contain the CCK motif. This study confirms that cyclotides may be regarded as a natural combinatorial template that displays a variety of peptide epitopes most likely targeted to a range of plant pests and pathogens.

Reflective web interface agent

Web interface agent is used with web browsers to assist users in searching and interactions with the WWW. It is used for a variety of purposes, such as web-enabled remote control, web interactive visualization, and e-commerce activities. User may be aware or unaware of its existence. The intelligence of interface agent consists in its capability of learning and decision-making in performing interactive functions on behalf of a user. However, since web is an open system environment, the reasoning mechanism in an agent should be able to adapt changes and make decisions on exceptional situations, and therefore use meta knowledge. This paper proposes a framework of Reflective Web Interface Agent (RWIA) that is to provide causal connections between the application interfaces and the knowledge model of the interface agent. A prototype is also implemented for the purpose of demonstration.

Reasoning about timeouts

In real-time programming a timeout mechanism allows exceptional behaviour, such as a lack of response, to be handled effectively, while not overly affecting the programming for the normal case. For. example, in a pump controller if the water level has gone below the minimum level and the pump is on and hence pumping in more water, then the water level should rise above the minimum level within a specified time. If not, there is a fault in the system and it should be shut down and an alarm raised. Such a situation can be handled by normal case code that determines when the level has risen above the minimum, plus a timeout case handling the situation when the specified time to reach the minimum has passed. In this paper we introduce a timeout mechanism, give it a formal definition in terms of more basic real-time commands, develop a refinement law for introducing a timeout clause to implement a specification, and give an example of using the law to introduce a timeout. The framework used is a machine-independent real-time programming language, which makes use of a deadline command to represent timing constraints in a machine-independent fashion. This allows a more abstract approach to handling timeouts.

Political leadership in France:from Charles de Gaulle to Nicolas Sarkozy

Political Leadership in France analyzes changes which have taken place over the last 50 years in French politics. When Charles de Gaulle came to power in 1958 the drama surrounding the Fourth Republic's collapse and the focus on an exceptional individual meant that he was able to confer a very particular style of leadership on the new Fifth Republic. De Gaulle's 'performance' was such that he transformed the nature of leadership politics in France, increasing the scope for personal leadership and the emphasis upon the exalted leader. This had major implications for the republic's institutions and for the role of political parties. The five Presidents who came after him – Pompidou, Giscard, Mitterrand, Chirac, and Sarkozy, as well as contenders for the presidency such as Segolene Royal and François Hollande – have each capitalized upon their own political 'persona' and their relationship to the French people. Gaffney takes a new approach to the subject, looking at the mythological and cultural as well as institutional conditions of political performance. This paperback edition includes a new preface.

Reasserting the distinctive character of share-holder remedies in Scotland - Wilson v Inverness Retail and Business Park Ltd

Juridical Review. Looks at the question of whether an individual shareholder has title to bring an action on the company's behalf in exceptional circumstances, as considered in the cases of Anderson v Hogg and Wilson v Inverness Retail & Business Park Ltd. Examines the difference between English and Scottish law in this area, notwithstanding the reliance on English case law in Scotland due to the small number of Scottish cases decided. Looks at progress towards the reform of company law and the impact it will have on a shareholder's title to sue.

Principles of marketing

Suitable for undergraduate Principles of Marketing courses, this classic textbook has provided many generations of marketing students with an exceptional introduction to marketing, written by one of the masters. With global examples and completely up-to-date with the latest marketing techniques, Principles of Marketing looks at the major decisions that marketing managers face in their efforts to balance an organisation’s objectives and resources against needs and opportunities in the global marketplace. Covering exciting new topics such as Sustainability, this text continues to be a leader in the field of marketing. New integrated video cases from companies such as HSBC, Land Rover and Amazon help to bring the subject alive.

Resonant cavity Fibre Bragg grating sensor interrogation

This thesis presents a novel high-performance approach to time-division-multiplexing (TDM) fibre Bragg grating (FBG) optical sensors, known as the resonant cavity architecture. A background theory of FBG optical sensing includes several techniques for multiplexing sensors. The limitations of current wavelength-division-multiplexing (WDM) schemes are contrasted against the technological and commercial advantage of TDM. The author’s hypothesis that ‘it should be possible to achieve TDM FBG sensor interrogation using an electrically switched semiconductor optical amplifier (SOA)’ is then explained. Research and development of a commercially viable optical sensor interrogator based on the resonant cavity architecture forms the remainder of this thesis. A fully programmable SOA drive system allows interrogation of sensor arrays 10km long with a spatial resolution of 8cm and a variable gain system provides dynamic compensation for fluctuating system losses. Ratiometric filter- and diffractive-element spectrometer-based wavelength measurement systems are developed and analysed for different commercial applications. The ratiometric design provides a low-cost solution that has picometre resolution and low noise using 4% reflective sensors, but is less tolerant to variation in system loss. The spectrometer design is more expensive, but delivers exceptional performance with picometre resolution, low noise and tolerance to 13dB system loss variation. Finally, this thesis details the interrogator’s peripheral components, its compliance for operation in harsh industrial environments and several examples of commercial applications where it has been deployed. Applications include laboratory instruments, temperature monitoring systems for oil production, dynamic control for wind-energy and battery powered, self-contained sub-sea strain monitoring.

The design of a real-time nowcasting system for localised weather

National meteorological offices are largely concerned with synoptic-scale forecasting where weather predictions are produced for a whole country for 24 hours ahead. In practice, many local organisations (such as emergency services, construction industries, forestry, farming, and sports) require only local short-term, bespoke, weather predictions and warnings. This thesis shows that the less-demanding requirements do not require exceptional computing power and can be met by a modern, desk-top system which monitors site-specific ground conditions (such as temperature, pressure, wind speed and direction, etc) augmented with above ground information from satellite images to produce `nowcasts'. The emphasis in this thesis has been towards the design of such a real-time system for nowcasting. Local site-specific conditions are monitored using a custom-built, stand alone, Motorola 6809 based sub-system. Above ground information is received from the METEOSAT 4 geo-stationary satellite using a sub-system based on a commercially available equipment. The information is ephemeral and must be captured in real-time. The real-time nowcasting system for localised weather handles the data as a transparent task using the limited capabilities of the PC system. Ground data produces a time series of measurements at a specific location which represents the past-to-present atmospheric conditions of the particular site from which much information can be extracted. The novel approach adopted in this thesis is one of constructing stochastic models based on the AutoRegressive Integrated Moving Average (ARIMA) technique. The satellite images contain features (such as cloud formations) which evolve dynamically and may be subject to movement, growth, distortion, bifurcation, superposition, or elimination between images. The process of extracting a weather feature, following its motion and predicting its future evolution involves algorithms for normalisation, partitioning, filtering, image enhancement, and correlation of multi-dimensional signals in different domains. To limit the processing requirements, the analysis in this thesis concentrates on an `area of interest'. By this rationale, only a small fraction of the total image needs to be processed, leading to a major saving in time. The thesis also proposes an extention to an existing manual cloud classification technique for its implementation in automatically classifying a cloud feature over the `area of interest' for nowcasting using the multi-dimensional signals.

Simultaneous grouping in cochlear implant listeners:can abrupt changes in level be used to segregate components from a complex tone?

A sudden increase in the amplitude of a component often causes its segregation from a complex tone, and shorter rise times enhance this effect. We explored whether this also occurs in implant listeners (n?=?8). Condition 1 used a 3.5-s “complex tone” comprising concurrent stimulation on five electrodes distributed across the array of the Nucleus CI24 implant. For each listener, the baseline stimulus level on each electrode was set at 50% of the dynamic range (DR). Two 1-s increments of 12.5%, 25%, or 50% DR were introduced in succession on adjacent electrodes within the “inner” three of those activated. Both increments had rise and fall times of 30 and 970 ms or vice versa. Listeners reported which increment was higher in pitch. Some listeners performed above chance for all increment sizes, but only for 50% increments did all listeners perform above chance. No significant effect of rise time was found. Condition 2 replaced amplitude increments with decrements. Only three listeners performed above chance even for 50% decrements. One exceptional listener performed well for 50% decrements with fall and rise times of 970 and 30 ms but around chance for fall and rise times of 30 and 970 ms, indicating successful discrimination based on a sudden rise back to baseline stimulation. Overall, the results suggest that implant listeners can use amplitude changes against a constant background to pick out components from a complex, but generally these must be large compared with those required in normal hearing. For increments, performance depended mainly on above-baseline stimulation of the target electrodes, not rise time. With one exception, performance for decrements was typically very poor.