Intrinsic disorder prediction from the analysis of multiple protein fold recognition models

Motivation: Intrinsic protein disorder is functionally implicated in numerous biological roles and is, therefore, ubiquitous in proteins from all three kingdoms of life. Determining the disordered regions in proteins presents a challenge for experimental methods and so recently there has been much focus on the development of improved predictive methods. In this article, a novel technique for disorder prediction, called DISOclust, is described, which is based on the analysis of multiple protein fold recognition models. The DISOclust method is rigorously benchmarked against the top.ve methods from the CASP7 experiment. In addition, the optimal consensus of the tested methods is determined and the added value from each method is quantified. Results: The DISOclust method is shown to add the most value to a simple consensus of methods, even in the absence of target sequence homology to known structures. A simple consensus of methods that includes DISOclust can significantly outperform all of the previous individual methods tested.

The impact of multiskilling on UK construction manpower

The overall significance of the construction and building services sector internationally cannot be overemphasised. In the UK, the industry currently accounts for 10% gross domestic product (GDP) and employs 2 million people, which is more than 1 in 14 of the total workforce. However, regardless of its output (approximately £65 billion annually) there has been a steady decline in the number of trade entrants into the construction and building services sector. Consequently, the available ‘pool of labour’ is inadequately resourced; productivity is low; the existing labour force is overstressed; there is an increase in site deaths; and a long-term labour shortage is envisaged. Today, the evidence seems to suggest that multiskilling is a tentative redress for ameliorating the skills crisis in the construction and building sectors. A 43-year time-series of data on 23 manpower attributes was evaluated as part of this investigation. The developed linear regression models show that the concept of multiskilling obeys the ‘law of diminishing returns'. That is, a weak relation was found between construction output and a three or more combination of manpower attributes. An optimisation model is prescribed for traditional trades.

Conformational studies of mixed-ligand copper(II) chelates. Crystal and molecular structure of (N,N-dimethyl-N′-ethyl-1,2-diaminoethane-(1-phenyl-1,3,-butanedionato)copper(II) perchlorate

The IR and ligand field spectra and the structure of the mixed-ligand compound [N,N-dimethyl-N′-ethyl-1,2-diaminoethane(1-phenyl-1,3-butanedionato)(perchlorato)copper(II)]), [Cu(dmeen)bzac(OClO3)], are reported. The structure was determined by single crystal X-ray diffraction analysis (triclinic, space group ). The structure is square pyramidal with the apical position occupied by one oxygen of the tetrahedral perchlorato group (distance from copper 2.452(5) Å). The plane of the phenyl ring is tilted forming an angle of 16.72(14)° with the plane of the β-dionato moiety. The nitrogenous base adopts the gauche conformation with torsional angle of 108.72(14)°. The ethyl group is cis oriented relative to the phenyl group, occupying the equatorial position with the vector of the carbon-nitrogen bond forming an angle of 143.9(3)° with the CuNN plane. The interactions of the adjacent axial hydrogen with an oxygen of the perchlorato group result in hydrogen bond formation. The IR spectra reveal that in the solid state the Br− or Cl− displace easily the ClO4− group. The shifts in the ligand field spectra indicate that polar solvents participate in donor-acceptor interactions with the metal centre along an axis perpendicular to the CuN2O2 plane.

Inside the black box: unravelling the development viability appraisal process

Over the last decade issues related to the financial viability of development have become increasingly important to the English planning system. As part of a wider shift towards the compartmentalisation of planning tasks, expert consultants are required to quantify, in an attempt to rationalise, planning decisions in terms of economic ‘viability’. Often with a particular focus on planning obligations, the results of development viability modelling have emerged as a key part of the evidence base used in site-specific negotiations and in planning policy formation. Focussing on the role of clients and other stakeholders, this paper investigates how development viability is tested in practice. It draws together literature on the role of calculative practices in policy formation, client feedback and influence in real estate appraisals and stakeholder engagement and consultation in the planning literature to critically evaluate the role of clients and other interest groups in influencing the production and use of development viability appraisal models. The paper draws upon semi-structured interviews with the main producers of development viability appraisals to conclude that, whilst appraisals have the potential to be biased by client and stakeholder interests, there are important controlling influences on potential opportunistic behaviour. One such control is local authorities’ weak understanding of development viability appraisal techniques which limits their capacity to question the outputs of appraisal models. However, this also is of concern given that viability is now a central feature of the town planning system.

Estrogens and thyroid hormone: Non-genomic effects are coupled to transcription.

Estrogens and thyroid hormones are regulators of important diverse physiological processes such as reproduction, thermogenesis, neural development, neural differentiation and cardiovascular functions. Both are ligands for receptors in the nuclear receptor superfamily, which act as ligand-dependent transcription factors, regulating transcription. However, estrogens and thyroid hormones also rapidly (within minutes or seconds) activate kinase cascades and calcium increases, presumably initiated at the cell membrane. We discuss the relevance of both modes of hormone action, including the membrane estrogen receptor, to physiology, with particular reference to lordosis behavior. We first showed that estrogen restricted to the membrane can, in fact, lead to subsequent increases in transcription from a consensus estrogen response element-based reporter in the neuroblastoma cell line, SK-N-BE(2)C. Using a novel hormonal paradigm, we also showed that the activation of protein kinase A, protein kinase C, mitogen activated protein kinase and increases in calcium were important in the ability of the membrane-limited estrogen to potentiate transcription. We discuss the source of calcium important in transcriptional potentiation. Since estrogens and thyroid hormones have common effects on neuroprotection, cognition and mood, we also hypothesized that crosstalk could occur between the rapid actions of thyroid hormones and the genomic actions of estrogens. In neural cells, we showed that triiodothyronine acting rapidly via MAPK can increase transcription by the nuclear estrogen receptor ERa from a consensus estrogen response element, possibly by the phosphorylation of the ERa. Novel mechanisms that link signals initiated by hormones from the membrane to the nucleus are physiologically relevant and can achieve neuroendocrine integration

Kazakhstan: long-term economic growth and the role of the oil sector

This study combines a narrative and modelling framework to analyse the development of Kazakhstan’s oil sector since its takeoff following separation from the USSR. As in the case of other emerging or transitional countries with large natural resource endowments, a key question is whether the exploitation of the natural resource is a benefit to longer term economic development: is it a curse, a blessing – or neither? Narrative evidence suggests that the establishment of good governance, in terms of institutions and policies, provides a background to sound long-term development, especially if combined with the development of sectors outside the natural resource sector, for example diversification into manufacturing and services, often through attracting FDI. The narrative is supported by econometric modelling of the relationship between domestic output, overseas output and exports of oil, which finds in favour of a sustained positive effect of oil exports on GDP. The model then provides a basis for projection of the growth in GDP given a consensus view of likely developments in the oil price.

Tenacity and silk investment of two orb weavers: considerations about diversification of the Araneoidea

Orbiculariae consists of two major clades: the cribellate Deinopidea and the much more diverse ecribellate Araneoidea. It has been hypothesized that the higher diversity of Araneoidea is a consequence of the superiority of the viscid orb web. However, this explanation seems incomplete: for example, cribellate silk may perform better than viscid silk in some contexts. Here, we consider the hypothesis that the diversification of Araneoidea was facilitated by changes in microhabitat occupation behavior due to the cheaper viscid orb web. In the present work we investigate the idea that the reduction in site tenacity caused by the emergence of the viscid orb web has led to an increase in the exploration of different resources and to a greater diversification of the Arancoidea through the evolutionary time. To test this idea, we evaluated the response of one cribellate orb web spider (Zosis geniculata Olivier 1789, Uloboridae) and one ecribellate orb web spider (Metazygia rogenhoferi Keyserling 1878, Arancidae) to abrupt prey absence. The changes in site tenacity and the day-to-day investment in web silk were evaluated. Spiders with three-dimensional webs tend to exhibit greater site tenacity than spiders making orb webs. Zosis geniculata and M. rogenhoferi show similar site tenacity when prey is ample. When prey is unavailable, the tenacity of the cribellate species increases while the tenacity of the ecribellate remains unchanged, and the silk investment of both species decreases. However, this decrease in silk investment is more extensive in Z. geniculata. These results coincide with the idea that a less costly ecribellate orb web leads to a lower tenacity and suggest that more frequent microhabitat abandonment in a context of insect radiation (Neiptera) leads to more diverse and opportunistic exploration of microhabitats that, in the long term, may be one explanation for the greater Araneoidea diversification.

Ligand dissociation from estrogen receptor is mediated by receptor dimerization: Evidence from molecular dynamics simulations

Estrogen Receptor (ER) is an important target for pharmaceutical design. Like other ligand-dependent transcription factors, hormone binding regulates ER transcriptional activity. Nevertheless, the mechanisms by which ligands enter and leave ERs and other nuclear receptors remain poorly understood. Here, we report results of locally enhanced sampling molecular dynamics simulations to identify dissociation pathways of two ER ligands [the natural hormone 17 beta-estradiol (E-2) and the selective ER modulator raloxifene (RAL)] from the human ER alpha ligand-binding domain in monomeric and dimeric forms. E-2 dissociation occurs via three different pathways in ER monomers. One resembles the mousetrap mechanism (Path I), involving repositioning of helix 12 (H12), others involve the separation of H8 and H11 (Path II), and a variant of this pathway at the bottom of the ligand-binding domain (Path II`). RAL leaves the receptor through Path I and a Path I variant in which the ligand leaves the receptor through the loop region between H11 and H12 (Path I`). Remarkably, ER dimerization strongly suppresses Paths II and II` for E-2 dissociation and modifies RAL escape routes. We propose that differences in ligand release pathways detected in the simulations for ER monomers and dimers provide an explanation for previously observed effects of ER quaternary state on ligand dissociation rates and suggest that dimerization may play an important, and hitherto unexpected, role in regulation of ligand dissociation rates throughout the nuclear receptor family.

A segurança do trabalho na indústria da construção civil

Identificando a segurança do trabalho como um fator de produtividade, a presente pesquisa analisa a situação da segurança do trabalho na Indústria da Construção civil no Rio Grande do Sul, mais especificamente na Região da Grande Porto Alegre, baseando-se em levantamento das condições de funcionamento dos Serviços Especializados em Segurança e Medicina do Trabalho de 14 empresas da região e na análise de 3.450 acidentes ocorridos nos anos de 1981, 1982 e 1º trimestre de 1983. O levantamento dos 3,450 acidentes, além de propiciar uma análise de custo do tempo de afastamento do acidentado, objetivou o conhecimento de variáveis que exercem influência na ocorrência de acidentes: a profissão, dia da semana, hora e etapa da obra (com quem, quando e onde ocorrem acidentes em um canteiro de obras). A partir desse estudo, sgo sugeridas medidas para a i-m plementação dos serviqos de segurança das empresas.

Interesse, ideologia & incompetência: a guerra do Iraque e o segundo consenso de Washington

Este projeto continua a avançar o programa de pesquisa que relaciona desenvolvimento econômico e democracia: pretende-se neste projeto dar um passo adiante e examinar como a democracia, uma vez consolidada como fruto do desenvolvimento capitalista, se torna ela própria um fator de desenvolvimento, particularmente quando ela deixa de ser uma mera democracia de elites para se tornar uma democracia de sociedade civil, na qual o debate público passa a ser um elemento central.

Anatomy of relationship significance: a critical realist exploration

Markets-as-networks (MAN) theorists contend, at least tacitly, the significance of business relationships to the firm – that is, business relationships contribute somewhat to corporate survival or growth. One does not deny the existence of significant business relationships but sustain, in contrast to the consensus within the MAN theory, that relationship significance should not be a self-evident assumption. For significance cannot be a taken-for-granted property of each and every one of the firm’s business relationships. The authors adopt explicitly a critical realist metatheoretical position in this conceptual paper and claim that relationship significance is an event of the business world, whose causes remain yet largely unidentified. Where the powers and liabilities of business relationships (i.e., relationship functions and dysfunctions) are put to work, inevitably under certain contingencies (namely the surrounding networks and markets), relationship effects ensue for the firm (often benefits in excess of sacrifices, i.e., relationship value) and as a consequence relationship significance is likely to be brought about. In addition, relationship significance can result from the dual impact that business relationships may have on the structure and powers and liabilities of the firm, that is, on corporate nature and scope, respectively.

Educação e sustentabilidae :Assentamento Maria da Paz - João Câmara/RN

This work is a research and action in the field of enviromental education, oriented for the construction of the land s distribuction of the Maria da Paz Settling, in João Câmara/RN, as process of social learning, collecive production of new knowledge, values and attitudes related to the environment. It was consolidated through a partnership beteween the UFRN (GERAH/DARQ and GEPEM/DEPED), MST and INCRA/RN. The drawing that represents the way the space organization of the settling was made constructed through effort of many people, in a process of dicussion with the community had as technical support the environment inventory (soil, vegetation, water resources, and others) allowing the agro-ecology zoning of the settlers participation conditions, their contradiction and conflicts, the challenges that appear in the search for consensus and the factor that creat chages

Dedução de Funções de Alívio para Priorização de Variantes de Chaveamento Adequadas à Eliminação de Sobrecargas

Eventually, violations of voltage limits at buses or admissible loadings of transmission lines and/or power transformers may occur by the power system operation. If violations are detected in the supervision process, corrective measures may be carried out in order to eliminate them or to reduce their intensity. Loading restriction is an extreme solution and should only be adopted as the last control action. Previous researches have shown that it is possible to control constraints in electrical systems by changing the network topology, using the technique named Corrective Switching, which requires no additional costs. In previous works, the proposed calculations for verifying the ability of a switching variant in eliminating an overload in a specific branch were based on network reduction or heuristic analysis. The purpose of this work is to develop analytical derivation of linear equations to estimate current changes in a specific branch (due to switching measures) by means of few calculations. For bus-bar coupling, derivations will be based on short-circuit theory and Relief Function methodology. For bus-bar splitting, a Relief Function will be derived based on a technique of equivalent circuit. Although systems of linear equations are used to substantiate deductions, its formal solution for each variant, in real time does not become necessary. A priority list of promising variants is then assigned for final check by an exact load flow calculation and a transient analysis using ATP Alternative Transient Program. At last, results obtained by simulation in networks with different features will be presented

As estratégias de negação variantes no inglês falado: uma comparação com o português

The general aim of this work is to verify the occurence of variant forms of negation in spoken English with the purpose of making a comparative study between the English and the Portuguese languages. As for Portuguese, we used as a matter of reference a study already made on negation. As for English, we analized a corpus of the North American English variant organized by a university in the United States. This study is based on the North American Functional Linguistics theoretical perspective, which considers relevant the study of language used in real situations of communicative interaction. The data analisys proved that there is at least one form of negative variant in spoken English which is not allowed by prescriptive grammar. This phenomenon turns out to be similar to Portuguese, which includes three variant strategies. According to the data obtained, it was possible to verify that the variant strategy used in English, from a contrastive point of view, corresponds to a negative strategy ruled by Portuguese prescriptive grammar. Finally, we discussed about the different conceptions of language, grammar and teaching, giving suggestions to colaborate to a productive and reflexive teaching of first or second language

A reafirmação do bairro:um estudo geo-histórico do bairro do Alecrim na cidade de Natal-RN

By the end of the 21st Century, economy globalization trends to show a velocity process through which market being expanded characterized by an intense going on of the internationalization of finance, after that marginalizing the periphery of the social spaces. It is clear to see that this process occurred in those less developed countries happens in an accentuated way just because income distribution that is so regressive and also because the insufficient enclosing of the social programs, we find this situation in a big part of Brazilian cities. The marginalizing social economical process observed in Natal, a city located in the east coast part of Northeast region in Brazil and that owns a population upper to 778 thousand in habitants is nearly linked to the extension of goods and services commerce. The installation of new urban activities in the city pointed out tourist activity as the greater impulsive thing in the phenomenon promotion, most of them aiming to promote Natal to the national and international scenery. It privilege strongly in the South zone with economical implementations such as shopping s centers, supermarkets, and home buildings condominiums leading to a loss of functionality of some traditional district located in central areas of the city. Notwithstanding, some spaces, for instance Alecrim district officially created in 1911, has notably resisted to the expansion of the urban process pointed out in Natal in the last years. So that this put Alecrim District as a district with originally characteristics reaffirmed along the historical process form old times. The predominance of some residential characteristics such as the incidence of some villages and a concentration of a big and confuse popular commerce distributed along streets puts Alecrim District as a resistant space in Natal. The same way analyze Alecrim District under the prism of Historic Geography because we understand this way it accomplishes a fundamental role in the theoretical methodological development of our work, just when we analyze the time as a variant in our object of study. It is still inside this theoretical field that we carry out a brief reviewing about quarter/district definition, under the optic from several registered and scientific resources taken into account along this work, because we understand that it was necessary to think this important spatial unit especially to know exactly what we are referring to as a district and so we can reaffirm Alecrim as an important and traditional district to Natal and it has been resisting to spatial transformation verified in the last years in Natal city. To give support to our reflection we used methodological tools related to inhabitants lifestyles knowledge and also the study of Alecrim District as a space that promote a certain centrality in Natal as some indicators to keep original characteristics in the district in Natal