Screening and analysis of bioactive compounds with biofingerprinting chromatogram analysis of traditional Chinese medicines targeting DNA by microdialysis/HPLC

Biofingerprinting chromatogram, analysis, which is defined as the comparison of fingerprinting chromatograms of the extract of traditional Chinese medicines (TCMs) before and after the interaction with biological systems (DNA, protein. cell. etc.), was proposed for screening and analysis of the multiple bioactive compounds in TCMs. A method of microdialysis sampling combined with high performance liquid chromatography (HPLC) was applied to the study of DNA-binding property for the extracts of TCMs. Seven compounds were found to bind to calf thymus DNA (ct-DNA) from the TCMs of Coptis chinensis Franch (Coptis), but only three ones from Phellodendron amurense Rupr. (Phellodendron) and none from Sophoraflavescens Ait. (Sophora) to bind to ct-DNA. respectively. Three of them were identified as berberine, palmatine and jatrorrhizine and their association constants (K) to ct-DNA were determined by microdialysis/HPLC. Competitive binding behaviors of them to ct-DNA were also investigated. © 2005 Elsevier B.V. All rights reserved.

Competitive relationships in a fertile grassland community - does size matter?

John Warren, Fred Wilson & Anita Diaz (2002). Competitive relationships in a fertile grassland community - does size matter? Oecologia, 132 (1) pp.125-130 Sponsorship: SEERAD / Leverhulme Trust RAE2008

A Recurrent Cooperative/Competitive Field for Segmentation of Magnetic Resonance Brain Imagery

The Grey-White Decision Network is introduced as an application of an on-center, off-surround recurrent cooperative/competitive network for segmentation of magnetic resonance imaging (MRI) brain images. The three layer dynamical system relaxes into a solution where each pixel is labeled as either grey matter, white matter, or "other" matter by considering raw input intensity, edge information, and neighbor interactions. This network is presented as an example of applying a recurrent cooperative/competitive field (RCCF) to a problem with multiple conflicting constraints. Simulations of the network and its phase plane analysis are presented.

A finite volume approach to geometrically non-linear stress analysis

In this past decade finite volume (FV) methods have increasingly been used for the solution of solid mechanics problems. This contribution describes a cell vertex finite volume discretisation approach to the solution of geometrically nonlinear (GNL) problems. These problems, which may well have linear material properties, are subject to large deformation. This requires a distinct formulation, which is described in this paper together with the solution strategy for GNL problem. The competitive performance for this procedure against the conventional finite element (FE) formulation is illustrated for a three dimensional axially loaded column.

D7.2 - Summary report of Value Chain analysis

The results presented in this deliverable depict relevant aspects of the EU based Applied Game industry and its competitive landscape. This preliminary overview of the primary target market for the RAGE ecosystem identifies some of the key issues to be further investigated by the RAGE WP7 team through stakeholders/market consultations commencing in year 2 of the project. These findings will form as an integral part of the baseline needed to formulate a sustainable exploitation strategy for the RAGE assets and ecosystem.

Determining factors of the innovative behavior of cooperatives: an analysis of the case of Castilla y León

Cooperatives have a long historical experience in the Spanish economy and have demonstrated their ability to compete against traditional firms in the market. To maintain this capability, while taking advantage of the competitive advantages associated with their idiosyncrasies as social economy enterprises, they should take into consideration that the economy is increasingly globalized and increasingly knowledge-based, especially with regards to technological content. As a consequence, the innovative capacity appears to be a key aspect in order to be able to challenge competitors. This article characterizes the innovative behavior of cooperatives in the region of Castile and Leon and analyses the internal and external factors affecting their innovative performance, based on data from a survey of 581 cooperatives. The results of the empirical analysis, which is performed by multivariate binary logistic regression on various types of innovation, lead us to identify the size of the organizations, the existence of planning, the R & D activities and the human capital as the main determining factors.

Intelligent Assembly Time Analysis Using a Digital Knowledge-Based Approach

The implementation of effective time analysis methods fast and accurately in the era of digital manufacturing has become a significant challenge for aerospace manufacturers hoping to build and maintain a competitive advantage. This paper proposes a structure oriented, knowledge-based approach for intelligent time analysis of aircraft assembly processes within a digital manufacturing framework. A knowledge system is developed so that the design knowledge can be intelligently retrieved for implementing assembly time analysis automatically. A time estimation method based on MOST, is reviewed and employed. Knowledge capture, transfer and storage within the digital manufacturing environment are extensively discussed. Configured plantypes, GUIs and functional modules are designed and developed for the automated time analysis. An exemplar study using an aircraft panel assembly from a regional jet is also presented. Although the method currently focuses on aircraft assembly, it can also be well utilized in other industry sectors, such as transportation, automobile and shipbuilding. The main contribution of the work is to present a methodology that facilitates the integration of time analysis with design and manufacturing using a digital manufacturing platform solution.

Developing a model of innovation implementation for UK SMEs: A path analysis and explanatory case analysis

Continuous large-scale changes in technology and the globalization of markets have resulted in the need for many SMEs to use innovation as a means of seeking competitive advantage where innovation includes both technological and organizational perspectives (Tapscott, 2009). However, there is a paucity of systematic and empirical research relating to the implementation of innovation management in the context of SMEs. The aim of this article is to redress this imbalance via an empirical study created to develop and test a model of innovation implementation in SMEs. This study uses Structural Equation Modelling (SEM) to test the plausibility of an innovation model, developed from earlier studies, as the basis of a questionnaire survey of 395 SMEs in the UK. The resultant model and construct relationship results are further probed using an explanatory multiple case analysis to explore ‘how’ and ‘why’ type questions within the model and construct relationships. The findings show that the
effects of leadership, people and culture on innovation implementation are mediated by business improvement activities relating to Total Quality Management/Continuous Improvement (TQM/CI) and product and process developments. It is concluded that SMEs have an opportunity to leverage existing quality and process improvement activities to move beyond continuous
improvement outcomes towards effective innovation implementation. The article concludes by suggesting areas suitable for further research.

A competitive enzyme-linked immunosorbent assay for determination of chloramphenicol

Chloramphenicol is a broad-spectrum antibiotic shown to have specific activity against a wide variety of organisms that are causative agents of several disease conditions in domestic animals. Chloramphenicol has been banned for use in food-producing animals for its serious adverse toxic effects in humans. Due to the harmful effects of chloramphenicol residues livestock products should be free of any traces of these residues. Several analytical methods are available for chloramphenicol analysis but sensitive methods are required in order to ensure that no traces of chloramphenicol residues are present in edible animal products. In order to prevent the illegal use of chloramphenicol, regulatory control of its residues in food of animal origin is essential. A competitive enzyme-linked immunosorbent assay for chloramphenicol has been locally developed and optimized for the detection of chloramphenicol in sheep serum. In the assay, chloramphenicol in the test samples and that in chloramphenicol-horseradish peroxidase conjugate compete for antibodies raised against the drug in camels and immobilized on a microtitre plate. Tetramethylbenzidine-hydrogen peroxide (TMB/H2O2) is used as chromogen-substrate system. The assay has a detection limit of 0.1 ng/mL of serum with a high specificity for chloramphenicol. Cross-reactivity with florfenicol, thiamphenicol, penicillin, tetracyclines and sulfamethazine was not observed. The assay was able to detect chloramphenicol concentrations in normal sheep serum for at least 1 week after intramuscular injection with the drug at a dose of 25 mg/kg body weight (b.w.). The assay can be used as a screening tool for chloramphenicol use in animals.

Analysis of HSC activity and compensatory Hox gene expression profile in Hoxb cluster mutant fetal liver cells

Overexpression of Hoxb4 in bone marrow cells promotes expansion of hematopoietic stem cell (HSC) populations in vivo and in vitro, indicating that this homeoprotein can activate the genetic program that determines self-renewal. However, this function cannot be solely attributed to Hoxb4 because Hoxb4(-/-) mice are viable and have an apparently normal HSC number. Quantitative polymerase chain reaction analysis showed that Hoxb4(-/-) c-Kit(+) fetal liver cells expressed moderately higher levels of several Hoxb cluster genes than control cells, raising the possibility that normal HSC activity in Hoxb4(-/-) mice is due to a compensatory up-regulation of other Hoxb genes. In this study, we investigated the competitive repopulation potential of HSCs lacking Hoxb4 alone, or in conjunction with 8 other Hoxb genes. Our results show that Hoxb4(-/-) and Hoxb1-b9(-/-) fetal liver cells retain full competitive repopulation potential and the ability to regenerate all myeloid and lymphoid lineages. Quantitative Hox gene expression profiling in purified c-KIt(+) Hoxb1-bg(-/-) fetal liver cells revealed an interaction between the Hoxa, b, and c clusters with variation in expression levels of Hoxa4, -a11, and -c4. Together, these studies show a complex network of genetic interactions between several Hox genes in primitive hematopoietic cells and demonstrate that HSCs lacking up to 30% of the active Hox genes remain fully competent.

Ensuring the statistical soundness of competitive gene set approaches: gene filtering and genome-scale coverage are essential

In this article, we focus on the analysis of competitive gene set methods for detecting the statistical significance of pathways from gene expression data. Our main result is to demonstrate that some of the most frequently used gene set methods, GSEA, GSEArot and GAGE, are severely influenced by the filtering of the data in a way that such an analysis is no longer reconcilable with the principles of statistical inference, rendering the obtained results in the worst case inexpressive. A possible consequence of this is that these methods can increase their power by the addition of unrelated data and noise. Our results are obtained within a bootstrapping framework that allows a rigorous assessment of the robustness of results and enables power estimates. Our results indicate that when using competitive gene set methods, it is imperative to apply a stringent gene filtering criterion. However, even when genes are filtered appropriately, for gene expression data from chips that do not provide a genome-scale coverage of the expression values of all mRNAs, this is not enough for GSEA, GSEArot and GAGE to ensure the statistical soundness of the applied procedure. For this reason, for biomedical and clinical studies, we strongly advice not to use GSEA, GSEArot and GAGE for such data sets.

Next generation planar waveguide detection of microcystins in freshwater and cyanobacterial extracts, utilising a novel lysis method for portable sample preparation and analysis

The study details the development of a fully validated, rapid and portable sensor based method for the on-site analysis of microcystins in freshwater samples. The process employs a novel lysis method for the mechanical lysis of cyanobacterial cells, with glass beads and a handheld frother in only 10min. The assay utilises an innovative planar waveguide device that, via an evanescent wave excites fluorescent probes, for amplification of signal in a competitive immunoassay, using an anti-microcystin monoclonal with cross-reactivity against the most common, and toxic variants. Validation of the assay showed the limit of detection (LOD) to be 0.78ngmL and the CCß to be 1ngmL. Robustness of the assay was demonstrated by intra- and inter-assay testing. Intra-assay analysis had % C.V.s between 8 and 26% and recoveries between 73 and 101%, with inter-assay analysis demonstrating % C.V.s between 5 and 14% and recoveries between 78 and 91%. Comparison with LC-MS/MS showed a high correlation (R=0.9954) between the calculated concentrations of 5 different Microcystis aeruginosa cultures for total microcystin content. Total microcystin content was ascertained by the individual measurement of free and cell-bound microcystins. Free microcystins can be measured to 1ngmL, and with a 10-fold concentration step in the intracellular microcystin protocol (which brings the sample within the range of the calibration curve), intracellular pools may be determined to 0.1ngmL. This allows the determination of microcystins at and below the World Health Organisation (WHO) guideline value of 1µgL. This sensor represents a major advancement in portable analysis capabilities and has the potential for numerous other applications.

Conceptual Design and Workspace Analysis of an Exechon-inspired Parallel Kinematic Machine

Inspired by the commercial application of the Exechon machine, this paper proposed a novel parallel kinematic machine (PKM) named Exe-Variant. By exchanging the sequence of kinematic pairs in each limb of the Exechon machine, the Exe-Variant PKM claims an arrangement of 2UPR/1SPR topology and consists of two identical UPR limbs and one SPR limb. The inverse kinematics of the 2UPR/1SPR parallel mechanism was firstly analyzed based on which a conceptual design of the Exe-Variant was carried out. Then an algorithm of reachable workspace searching for the Exe-Variant and the Exchon was proposed. Finally, the workspaces of two example systems of the Exechon and the Exe-Variant with approximate dimensions were numerically simulated and compared. The comparison shows that the Exe-Variant possesses a competitive workspace with the Exechon machine, indicating it can be used as a promising reconfigurable module in a hybrid 5-DOF machine tool system.

Managerial Representations of Achieving Competitive Advantage in Architectural Firms within the United Kingdom

Purpose - The purpose is to unearth managerial representations of achieving competitive advantage in relation to architectural firms operating within the United Kingdom (UK).
Design/Methodology/Approach - A sequential qualitative methodology is applied, underpinned by nine managerial interviews in five architectural practices; all of which are analysed using computer assisted qualitative data analysis software.
Findings - 108 representations are identified with highly rated concepts discussed in detail. Subsequently, the leading concepts include reputation, client satisfaction, fees and staff resources, among others.
Research Limitations/Implications - There are numerous studies conducted on this subject; however, there has been no research done to date documenting managerial representations within the UK on achieving competitive advantage in the context of architectural firms.
Practical Implications – The need for architectural firms to develop a competitive advantage within their market sector is ever more apparent, particularly during times of increased competitiveness.
Originality/Value – This paper fulfils a gap in knowledge by contributing to underlying research on the subject of competitive advantage, but focusing on the managerial representations, specifically within UK practices. The findings are of relevance to architects in both the UK and beyond, as well as perhaps forming the basis of identifying further research with the area.

Nucella lapillus: imposex transcriptome analysis and phenotypic plasticity

O conhecimento de mecanismos de genómica funcional tem sido maioritariamente adquirido pela utilização de organismos modelo que são mantidos em condições laboratoriais. Contudo, estes organismos não reflectem as respostas a alterações ambientais. Por outro lado, várias espécies, ecologicamente bem estudadas, reflectem bem as interacções entre genes e ambiente mas que, das quais não existem recursos genéticos disponíveis. O imposex, caracterizado pela superimposição de caracteres sexuais masculinos em fêmeas, é induzido pelo tributilestanho (TBT) e trifenilestanho (TPT) e representa um dos melhores exemplos de disrupção endócrina com causas antropogénicas no ambiente aquático. Com o intuito de elucidar as bases moleculares deste fenómeno, procedeu-se à combinação das metodologias de pirosequenciação (sequenciação 454 da Roche) e microarrays (Agilent 4*180K) de forma a contribuir para um melhor conhecimento desta interacção gene-ambiente no gastrópode Nucella lapillus, uma espécie sentinela para imposex. O trancriptoma de N. lapillus foi sequenciado, reconstruído e anotado e posteriormente utilizado para a produção de um “array” de nucleótidos. Este array foi então utilizado para explorar níveis de expressão génica em resposta à contaminação por TBT. Os resultados obtidos confirmaram as hipóteses anteriormente propostas (esteróidica, neuroendócrina, retinóica) e adicionalmente revelou a existência de potenciais novos mecanismos envolvidos no fenómeno imposex. Evidência para alvos moleculares de disrupção endócrina não relacionados com funções reprodutoras, tais como, sistema imunitário, apoptose e supressores de tumores, foram identificados. Apesar disso, tendo em conta a forte componente reprodutiva do imposex, esta componente funcional foi a mais explorada. Assim, factores de transcrição e receptores nucleares lipofílicos, funções mitocondriais e actividade de transporte celular envolvidos na diferenciação de géneros estão na base de potenciais novos mecanismos associados ao imposex em N. lapillus. Em particular, foi identificado como estando sobre-expresso, um possível homólogo do receptor nuclear “peroxisome proliferator-activated receptor gamma” (PPARγ), cuja função na indução de imposex foi confirmada experimentalmente in vivo após injecção dos animais com Rosiglitazone, um conhecido ligando de PPARγ em vertebrados. De uma forma geral, os resultados obtidos mostram que o fenómeno imposex é um mecanismo complexo, que possivelmente envolve a cascata de sinalização envolvendo o receptor retinoid X (RXR):PPARγ “heterodimer” que, até à data não foi descrito em invertebrados. Adicionalmente, os resultados obtidos apontam para alguma conservação de mecanismos de acção envolvidos na disrupção endócrina em invertebrados e vertebrados. Finalmente, a informação molecular produzida e as ferramentas moleculares desenvolvidas contribuem de forma significativa para um melhor conhecimento do fenómeno imposex e constituem importantes recursos para a continuação da investigação deste fenómeno e, adicionalmente, poderão vir a ser aplicadas no estudo de outras respostas a alterações ambientais usando N. lapillus como organismo modelo. Neste sentido, N. lapillus foi também utilizada para explorar a adaptação na morfologia da concha em resposta a alterações naturais induzidas por acção das ondas e pelo risco de predação por caranguejos. O contributo da componente genética, plástica e da sua interacção para a expressão fenotípica é crucial para compreender a evolução de caracteres adaptativos a ambientes heterogéneos. A contribuição destes factores na morfologia da concha de N. lapillus foi explorada recorrendo a transplantes recíprocos e experiências laboratoriais em ambiente comum (com e sem influência de predação) e complementada com análises genéticas, utilizando juvenis provenientes de locais representativos de costas expostas e abrigadas da acção das ondas. As populações estudadas são diferentes geneticamente mas possuem o mesmo cariótipo. Adicionalmente, análises morfométricas revelaram plasticidade da morfologia da concha em ambas as direcções dos transplantes recíprocos e também a retenção parcial, em ambiente comum, da forma da concha nos indivíduos da F2, indicando uma correlação positiva (co-gradiente) entre heritabilidade e plasticidade. A presença de estímulos de predação por caranguejos estimulou a produção de conchas com labros mais grossos, de forma mais evidente em animais recolhidos de costas expostas e também provocou alterações na forma da concha em animais desta proveniência. Estes dados sugerem contra-gradiente em alterações provocadas por predação na morfologia da concha, na produção de labros mais grossos e em níveis de crescimento. O estudo das interacções gene-ambiente descritas acima demonstram a actual possibilidade de produzir recursos e conhecimento genómico numa espécie bem caracterizada ecologicamente mas com limitada informação genómica. Estes recursos permitem um maior conhecimento biológico desta espécie e abrirão novas oportunidades de investigação, que até aqui seriam impossíveis de abordar.