A new method for identification of protein (sub)families in a set of proteins based on hydropathy distribution in proteins

Structural similarity among proteins is reflected in the distribution of hydropathicity along the amino acids in the protein sequence. Similarities in the hydropathy distributions are obvious for homologous proteins within a protein family. They also were observed for proteins with related structures, even when sequence similarities were undetectable. Here we present a novel method that employs the hydropathy distribution in proteins for identification of (sub)families in a set of (homologous) proteins. We represent proteins as points in a generalized hydropathy space, represented by vectors of specifically defined features. The features are derived from hydropathy of the individual amino acids. Projection of this space onto principal axes reveals groups of proteins with related hydropathy distributions. The groups identified correspond well to families of structurally and functionally related proteins. We found that this method accurately identifies protein families in a set of proteins, or subfamilies in a set of homologous proteins. Our results show that protein families can be identified by the analysis of hydropathy distribution, without the need for sequence alignment. (C) 2005 Wiley-Liss, Inc.

Uniqueness criteria for continuous-time Markov chains with general transition structures

We derive necessary and sufficient conditions for the existence of bounded or summable solutions to systems of linear equations associated with Markov chains. This substantially extends a famous result of G. E. H. Reuter, which provides a convenient means of checking various uniqueness criteria for birth-death processes. Our result allows chains with much more general transition structures to be accommodated. One application is to give a new proof of an important result of M. F. Chen concerning upwardly skip-free processes. We then use our generalization of Reuter's lemma to prove new results for downwardly skip-free chains, such as the Markov branching process and several of its many generalizations. This permits us to establish uniqueness criteria for several models, including the general birth, death, and catastrophe process, extended branching processes, and asymptotic birth-death processes, the latter being neither upwardly skip-free nor downwardly skip-free.

Asparinins, asparosides, curillins, curillosides and shavatarins: structural clarification with the isolation of shatavarin V, a new steroidal saponin from the root of Asparagus racemosus

A new steroidal saponin, shatavarin V, (3-O-{[alpha-L-rhamnopyranosy](1-2)][beta-D-glucopyranosyl(1 -> 4)]-beta-D-glucopyranosyl}-(25S)-5 beta-spirostan-3 beta-ol), was isolated from the roots of Asparagus racemosus by RP-HPLC, and its structure determined by 1D and 2D NMR studies. This data permits clarification of the structures reported for several known saponins: asparinins A and B; asparosides A and B; curillin H; curillosides G and H and shavatarins I and IV. (c) 2006 Elsevier Ltd. All rights reserved.

Alpha-selenoconotoxins, a new class of potent alpha(7) neuronal nicotinic receptor antagonists

Disulfide bonds are important structural motifs that play an essential role in maintaining the conformational stability of many bioactive peptides. Of particular importance are the conotoxins, which selectively target a wide range of ion channels that are implicated in numerous disease states. Despite the enormous potential of conotoxins as therapeutics, their multiple disulfide bond frameworks are inherently unstable under reducing conditions. Reduction or scrambling by thiol-containing molecules such as glutathione or serum albumin in intracellular or extracellular environments such as blood plasma can decrease their effectiveness as drugs. To address this issue, we describe a new class of selenoconotoxins where cysteine residues are replaced by selenocysteine to form isosteric and non-reducible diselenide bonds. Three isoforms of alpha-conotoxin ImI were synthesized by t-butoxycarbonyl chemistry with systematic replacement of one([ Sec(2,8)] ImI or [Sec(3,12)] ImI), or both([Sec(2,3,8,12)] ImI) disulfide bonds with a diselenide bond. Each analogue demonstrated remarkable stability to reduction or scrambling under a range of chemical and biological reducing conditions. Three-dimensional structural characterization by NMR and CD spectroscopy indicates conformational preferences that are very similar to those of native ImI, suggesting fully isomorphic structures. Additionally, full bioactivity was retained at the alpha(7) nicotinic acetylcholine receptor, with each seleno-analogue exhibiting a dose-response curve that overlaps with wild-type ImI, thus further supporting an isomorphic structure. These results demonstrate that selenoconotoxins can be used as highly stable scaffolds for the design of new drugs.

No more free beer tomorrow? Economic policy and outcomes in Australia and New Zealand since 1984

There are no controlled experiments in macroeconomic policy, nor in systematic programs of microeconomic reform, but a comparison between New Zealand and Australia over the period since 1984 provides as close an approach to such an experiment as is ever likely to be possible. From quite similar starting points the two countries pursued liberal reform programs that differed sharply, mainly as a result of exogenous differences in constitutional structures and the personal styles of the central actors. Australia followed a more cautious, piecemeal, consensus-based approach, whereas New Zealand, in contrast, adopted a radical, rapid, 'purist' platform. The NZ reform package was generally seen by contemporary commentators as representing a 'textbook' model for best practice reform. However, Australia since 1984 has performed much better than New Zealand, whose per capita GDP growth indeed ranked at or near the bottom of the OECD. In this paper, we assess a variety of explanations for the divergences in policies and outcomes.

A new indexing method for high dimensional dataset

Indexing high dimensional datasets has attracted extensive attention from many researchers in the last decade. Since R-tree type of index structures are known as suffering curse of dimensionality problems, Pyramid-tree type of index structures, which are based on the B-tree, have been proposed to break the curse of dimensionality. However, for high dimensional data, the number of pyramids is often insufficient to discriminate data points when the number of dimensions is high. Its effectiveness degrades dramatically with the increase of dimensionality. In this paper, we focus on one particular issue of curse of dimensionality; that is, the surface of a hypercube in a high dimensional space approaches 100% of the total hypercube volume when the number of dimensions approaches infinite. We propose a new indexing method based on the surface of dimensionality. We prove that the Pyramid tree technology is a special case of our method. The results of our experiments demonstrate clear priority of our novel method.

Ontology ranking based on the analysis of concept structures

In view of the need to provide tools to facilitate the re-use of existing knowledge structures such as ontologies, we present in this paper a system, AKTiveRank, for the ranking of ontologies. AKTiveRank uses as input the search terms provided by a knowledge engineer and, using the output of an ontology search engine, ranks the ontologies. We apply a number of metrics in an attempt to investigate their appropriateness for ranking ontologies, and compare the results with a questionnaire-based human study. Our results show that AKTiveRank will have great utility although there is potential for improvement.

Momentum profits in alternative stock market structures

The aim of this study is to examine the relationship between momentum profitability and the stock market trading mechanism and is motivated by recent changes to the trading systems that have taken place on the London Stock Exchange. Since 1975 the London stock market has employed three different trading systems: a floor based system, a computerized dealer system called SEAQ and the automated auction system SETS. Since each new trading system has reduced the level of execution costs, one might expect, a priori, the magnitude of momentum profits to decline with each amendment to the trading system. However, the opposite empirical result is found showing that shares trading on the automated system generate higher momentum profits than those trading on the floor system and companies trading on the SETS system display greater momentum profitability than those trading on SEAQ. Our empirical results concur with the theoretical findings of the trader’s hesitation model of Du [Du, J., 2002. Heterogeneity in investor confidence and asset market under- and overreaction. Working paper] and the empirical findings of Arena et al. [Arena, M., Haggard, S., Yan, X., Price momentum and idiosyncratic volatility. Financial Review, in press].

Mixed communities: a new approach to spatially-concentrated poverty in England

This article examines the adoption, by the New Labour government, of a mixed communities approach to the renewal of disadvantaged neighbourhoods in England. It argues that while there are continuities with previous policy, the new approach represents a more neoliberal policy turn in three respects: its identification of concentrated poverty as the problem; its faith in market-led regeneration; and its alignment with a new urban policy agenda in which cities are gentrified and remodelled as sites for capital accumulation through entrepreneurial local governance. The article then draws on evidence from the early phases of the evaluation of the mixed community demonstration projects to explore how the new policy approach is playing out at a local level, where it is layered upon existing policies, politics and institutional relationships. Tensions between neighbourhood and strategic interests, community and capital are evident as the local projects attempt neighbourhood transformation, while seeking to protect the rights and interests of existing residents. Extensive community consultation efforts run parallel with emergent governance structures, in which local state and capital interests combine and communities may effectively be disempowered. Policies and structures are still evolving and it is not yet entirely clear how these tensions will be resolved, especially in the light of a collapsing housing market, increased poverty and demand for affordable housing, and a shortage of private investment.

Fiber Bragg grating structures inscribed using 800nm femtosecond laser in single- and multi-core mid-IR glass fibers with their spectral, thermal and strain properties

Single- and multi-core passive and active germanate and tellurite glass fibers represent a new class of fiber host for in-fiber photonics devices and applications in mid-IR wavelength range, which are in increasing demand. Fiber Bragg grating (FBG) structures have been proven as one of the most functional in-fiber devices and have been mass-produced in silicate fibers by UV-inscription for almost countless laser and sensor applications. However, because of the strong UV absorption in germanate and tellurite fibers, FBG structures cannot be produced by UVinscription. In recent years femtosecond (fs) lasers have been developed for laser machining and microstructuring in a variety of glass fibers and planar substrates. A number of papers have been reported on fabrication of FBGs and long-period gratings in optical fibers and also on the photosensitivity mechanism using 800nm fs lasers. In this paper, we demonstrate for the first time the fabrication of FBG structures created in passive and active single- and three-core germanate and tellurite glass fibers by using 800nm fs-inscription and phase mask technique. With a fs peak power intensity in the order of 1011W/cm2, the FBG spectra with 2nd and 3rd order resonances at 1540nm and 1033nm in a single-core germanate glass fiber and 2nd order resonances between ~1694nm and ~1677nm with strengths up to 14dB in all three cores of three-core passive and active tellurite fibers were observed. Thermal and strain properties of the FBGs made in these mid-IR glass fibers were characterized, showing an average temperature responsivity of ~20pm/°C and a strain sensitivity of 1.219±0.003pm/µe.

The interplay between microscopic and mesoscopic structures in complex networks

Understanding a complex network's structure holds the key to understanding its function. The physics community has contributed a multitude of methods and analyses to this cross-disciplinary endeavor. Structural features exist on both the microscopic level, resulting from differences between single node properties, and the mesoscopic level resulting from properties shared by groups of nodes. Disentangling the determinants of network structure on these different scales has remained a major, and so far unsolved, challenge. Here we show how multiscale generative probabilistic exponential random graph models combined with efficient, distributive message-passing inference techniques can be used to achieve this separation of scales, leading to improved detection accuracy of latent classes as demonstrated on benchmark problems. It sheds new light on the statistical significance of motif-distributions in neural networks and improves the link-prediction accuracy as exemplified for gene-disease associations in the highly consequential Online Mendelian Inheritance in Man database. © 2011 Reichardt et al.

The development of a new compiler-compiler front-end

The increasing cost of developing complex software systems has created a need for tools which aid software construction. One area in which significant progress has been made is with the so-called Compiler Writing Tools (CWTs); these aim at automated generation of various components of a compiler and hence at expediting the construction of complete programming language translators. A number of CWTs are already in quite general use, but investigation reveals significant drawbacks with current CWTs, such as lex and yacc. The effective use of a CWT typically requires a detailed technical understanding of its operation and involves tedious and error-prone input preparation. Moreover, CWTs such as lex and yacc address only a limited aspect of the compilation process; for example, actions necessary to perform lexical symbol valuation and abstract syntax tree construction must be explicitly coded by the user. This thesis presents a new CWT called CORGI (COmpiler-compiler from Reference Grammar Input) which deals with the entire `front-end' component of a compiler; this includes the provision of necessary data structures and routines to manipulate them, both generated from a single input specification. Compared with earlier CWTs, CORGI has a higher-level and hence more convenient user interface, operating on a specification derived directly from a `reference manual' grammar for the source language. Rather than developing a compiler-compiler from first principles, CORGI has been implemented by building a further shell around two existing compiler construction tools, namely lex and yacc. CORGI has been demonstrated to perform efficiently in realistic tests, both in terms of speed and the effectiveness of its user interface and error-recovery mechanisms.

Strategic orientations in practice:Exploring the strategic belief structures of line-managers embedded in practice

Recently researchers have started to investigate the cognitive strategic orientations of individual top managers and have pointed out these may be key in determining the direction and success of their organizations in terms of performance, but they have been unable to effectively operationalize this notion in empirical research and this is holding up knowledge development. To make a contribution that helps overcome this limitation a theoretical framework is developed which specifies the different possible cognitive strategic orientations of top managers as well as those of managers at lower organizational levels involved in the strategy process. This theoretical framework is investigated in the empirical phase of the study into strategic orientations in practice. Additional contributions to knowledge of strategic orientation are made in three main domains. Firstly, current knowledge of strategic orientation is largely limited to analysis at the level of the firm whereas there is a lack of understanding of any relationships with practice at lower organizational levels. The exploratory research undertaken for this thesis contributes to new knowledge of different rational, developmental and interactive strategic orientations of front-line managers and this contributes to a cognitive explanation for emergent strategy linked to strategy processes embedded in practice. In theorising the presence of different strategic orientations in practice the discussion highlights the importance of network and spatial embeddedness within enacted environments. Secondly, a contribution to further knowledge of the links between strategy processes and the content of strategies within a retail context is made. The research highlights different strategy processes used in practice by retail front-line managers in a branch network of stores and these are linked to consequences such as different objectives, performance expectations and the fulfilment of personal goals. Thirdly, a contribution to research methodology is made by addressing problems associated with the comparison of cognitive maps.

System identification of linear vibrating structures

Methods of dynamic modelling and analysis of structures, for example the finite element method, are well developed. However, it is generally agreed that accurate modelling of complex structures is difficult and for critical applications it is necessary to validate or update the theoretical models using data measured from actual structures. The techniques of identifying the parameters of linear dynamic models using Vibration test data have attracted considerable interest recently. However, no method has received a general acceptance due to a number of difficulties. These difficulties are mainly due to (i) Incomplete number of Vibration modes that can be excited and measured, (ii) Incomplete number of coordinates that can be measured, (iii) Inaccuracy in the experimental data (iv) Inaccuracy in the model structure. This thesis reports on a new approach to update the parameters of a finite element model as well as a lumped parameter model with a diagonal mass matrix. The structure and its theoretical model are equally perturbed by adding mass or stiffness and the incomplete number of eigen-data is measured. The parameters are then identified by an iterative updating of the initial estimates, by sensitivity analysis, using eigenvalues or both eigenvalues and eigenvectors of the structure before and after perturbation. It is shown that with a suitable choice of the perturbing coordinates exact parameters can be identified if the data and the model structure are exact. The theoretical basis of the technique is presented. To cope with measurement errors and possible inaccuracies in the model structure, a well known Bayesian approach is used to minimize the least squares difference between the updated and the initial parameters. The eigen-data of the structure with added mass or stiffness is also determined using the frequency response data of the unmodified structure by a structural modification technique. Thus, mass or stiffness do not have to be added physically. The mass-stiffness addition technique is demonstrated by simulation examples and Laboratory experiments on beams and an H-frame.