Development and validation of a ultra performance LC-ESI/MS method for analysis of metabolic phenotypes of healthy men in day and night urine samples

Ultra-performance LC coupled to quadrupole TOF/MS (UPLC-QTOF/MS) in positive and negative ESI was developed and validated to analyze metabolite profiles for urine from healthy men during the day and at night. Data analysis using principal components analysis (PCA) revealed differences between metabolic phenotypes of urine in healthy men during the day and at night. Positive ions with mass-to-charge ratio (m/z) 310.24 (5.35 min), 286.24 (4.74 min) and 310.24 (5.63 min) were elevated in the urine from healthy men at night compared to that during the day. Negative ions elevated in day urine samples of healthy men included m/z 167.02 (0.66 min), 263.12 (2.55 min) and 191.03 (0.73 min), whilst ions m/z 212.01 (4.77 min) were at a lower concentration in urine of healthy men during the day compared to that at night. The ions m/z 212.01 (4.77 min), 191.03 (0.73 min) and 310.24 (5.35 min) preliminarily correspond to indoxyl sulfate, citric acid and N-acetylneuraminic acid, providing further support for an involvement of phenotypic difference in urine of healthy men in day and night samples, which may be associated with notably different activities of gut microbiota, velocity of tricarboxylic acid cycle and activity of sialic acid biosynthesis in healthy men as regulated by circadian rhythm of the mammalian bioclock.

Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma

Cancer can be defined as a deregulation or hyperactivity in the ongoing network of intracellular and extracellular signaling events. Reverse phase protein microarray technology may offer a new opportunity to measure and profile these signaling pathways, providing data on post-translational phosphorylation events not obtainable by gene microarray analysis. Treatment of ovarian epithelial carcinoma almost always takes place in a metastatic setting since unfortunately the disease is often not detected until later stages. Thus, in addition to elucidation of the molecular network within a tumor specimen, critical questions are to what extent do signaling changes occur upon metastasis and are there common pathway elements that arise in the metastatic microenvironment. For individualized combinatorial therapy, ideal therapeutic selection based on proteomic mapping of phosphorylation end points may require evaluation of the patient's metastatic tissue. Extending these findings to the bedside will require the development of optimized protocols and reference standards. We have developed a reference standard based on a mixture of phosphorylated peptides to begin to address this challenge.

A conceptual analysis of strategic capability development within product innovation projects

Strategic capability development refers to the renewal of the organisational capabilities which are sources of competitive advantage. The aim of this paper is to examine how strategic capability and competitive advantage build up over time. Recent literature points to the integration of dynamic capability and ambidexterity perspectives in explaining organisational capability development. Literature analysis reveals the role of knowledge integration and product innovation in integrating dynamic capability and ambidexterity. However, little attention has yet been paid to knowledge integration within innovation projects as a context for capability development. Accordingly, this paper aims to develop a conceptual framework for strategic capability development focusing on the role of knowledge integration within product innovation projects. This framework contributes to identifying and emphasising the role of micro processes in capability renewal which in turn enhances our understanding of strategic capability development.

Commuting mode choice in transit oriented development: Disentangling the effects of competitive neighbourhoods, travel attitudes, and self-selection

This research identifies the commuting mode choice behaviour of 3537 adults living in different types of transit oriented development (TOD) in Brisbane by disentangling the effects of their “evil twin” transit adjacent developments (TADs), and by also controlling for residential self-selection, travel attitudes and preferences, and socio-demographic effects. A TwoStep cluster analysis was conducted to identify the natural groupings of respondents’ living environment based on six built environment indicators. The analysis resulted in five types of neighbourhoods: urban TODs, activity centre TODs, potential TODs, TADs, and traditional suburbs. HABITAT survey data were used to derive the commute mode choice behaviour of people living in these neighbourhoods. In addition, statements reflecting both respondents’ travel attitudes and living preferences were also collected as part of the survey. Factor analyses were conducted based on these statements and these derived factors were then used to control for residential self-selection. Four binary logistic regression models were estimated, one for each of the travel modes used (e.g. public transport, active transport, less sustainable transport such as the car/taxi, and other), to differentiate between the commuting behaviour of people living in the five types of neighbourhoods. The findings verify that urban TODs enhance the use of public transport and reduce car usage. No significant difference was found in the commuting behaviour between respondents living in traditional suburbs and TADs. The results confirm the hypothesis that TADs are the “evil twin” of TODs. The data indicates that TADs and the mode choices of residents in these neighbourhoods is a missed transport policy opportunity. Further policy efforts are required for a successive transition of TADs into TODs in order to realise the full benefits of these. TOD policy should also be integrated with context specific TOD design principles.

A Doubly curved Quadrilateral finite-element for the analysis of laminated anisotropic thin shells of revoution

The details of development of the stiffness matrix for a doubly curved quadrilateral element suited for static and dynamic analysis of laminated anisotropic thin shells of revolution are reported. Expressing the assumed displacement state over the middle surface of the shell as products of one-dimensional first order Hermite polynomials, it is possible to ensure that the displacement state for the assembled set of such elements, is geometrically admissible. Monotonic convergence of total potential energy is therefore possible as the modelling is successively refined. Systematic evaluation of performance of the element is conducted, considering various examples for which analytical or other solutions are available.

Global Nursing Issues and Development: Analysis of World Health Organization Documents

Purpose To analyze World Health Organization (WHO) documents to identify global nursing issues and development. Design Qualitative content analysis. Methods Documents published by the six WHO regions between 2007 and 2012 and with key words related to nurse/midwife or nursing/midwifery were included. Themes, categories, and subcategories were derived. The final coding reached 80% agreement among three independent coders, and the final coding for the discrepant coding was reached by consensus. Findings Thirty-two documents from the regions of Europe (n = 19), the Americas (n = 6), the Western Pacific (n = 4), Africa (n = 1), the Eastern Mediterranean (n = 1), and Southeast Asia (n = 1) were examined. A total of 385 units of analysis dispersed in 31 subcategories under four themes were derived. The four themes derived (number of unit of analysis, %) were Management & Leadership (206, 53.5), Practice (75, 19.5), Education (70, 18.2), and Research (34, 8.8). Conclusions The key nursing issues of concern at the global level are workforce, the impacts of nursing in health care, professional status, and education of nurses. International alliances can help advance nursing, but the visibility of nursing in the WHO needs to be strengthened. Clinical Relevance Organizational leadership is important in order to optimize the use of nursing competence in practice and inform policy makers regarding the value of nursing to promote people's health.

Fluorescence in situ hybridization analysis of hindgut bacteria associated with the development of equine laminitis

In the article 'Fluorescence in situ hybridization analysis of hindgut bacteria associated with the development of equine laminitis' (Milinovich et al., 2007), it is found that with reference to Horse 1, the histological signs of laminitis were first observed at 12 h post-oligofructose administration, and not 30 h as was indicated in the Results section under the subheading 'Induction of Laminitis' and in Fig. 1.

Development of near infrared analysis of faeces to estimate non-grass proportions in diets selected by cattle grazing tropical pastures

Grass (monocots) and non-grass (dicots) proportions in ruminant diets are important nutritionally because the non-grasses are usually higher in nutritive value, particularly protein, than the grasses, especially in tropical pastures. For ruminants grazing tropical pastures where the grasses are C-4 species and most non-grasses are C-3 species, the ratio of C-13/C-12 in diet and faeces, measured as delta C-13 parts per thousand, is proportional to dietary non-grass%. This paper describes the development of a faecal near infrared (NIR) spectroscopy calibration equation for predicting faecal delta C-13 from which dietary grass and non-grass proportions can be calculated. Calibration development used cattle faeces derived from diets containing only C-3 non-grass and C-4 grass components, and a series of expansion and validation steps was employed to develop robustness and predictive reliability. The final calibration equation contained 1637 samples and faecal delta C-13 range (parts per thousand) of [12.27]-[27.65]. Calibration statistics were: standard error of calibration (SEC) of 0.78, standard error of cross-validation (SECV) of 0.80, standard deviation (SD) of reference values of 3.11 and R-2 of 0.94. Validation statistics for the final calibration equation applied to 60 samples were: standard error of prediction (SEP) of 0.87, bias of -0.15, R-2 of 0.92 and RPD of 3.16. The calibration equation was also tested on faeces from diets containing C-4 non-grass species or temperate C-3 grass species. Faecal delta C-13 predictions indicated that the spectral basis of the calibration was not related to C-13/C-12 ratios per se but to consistent differences between grasses and non-grasses in chemical composition and that the differences were modified by photosynthetic pathway. Thus, although the calibration equation could not be used to make valid faecal delta C-13 predictions when the diet contained either C-3 grass or C-4 non-grass, it could be used to make useful estimates of dietary non-grass proportions. It could also be ut :sed to make useful estimates of non-grass in mixed C-3 grass/non-grass diets by applying a modified formula to calculate non-grass from predicted faecal delta C-13. The development of a robust faecal-NIR calibration equation for estimating non-grass proportions in the diets of grazing cattle demonstrated a novel and useful application of NIR spectroscopy in agriculture.

Multiobjective Analysis of Irrigation Planning in River Basin Development

A river basin that is extensively developed in the downstream reaches and that has a high potential for development in the upper reaches is considered for irrigation planning. A four-reservoir system is modeled on a monthly basis by using a mathematical programing (LP) formulation to find optimum cropping patterns, subject to land, water, and downstream release constraints. The model is applied to a fiver basin in India. Two objectives, maximizing net economic benefits and maximizing irrigated cropped area, considered in the model are analyzed in the context of multiobjective planning, and the tradeoffs are discussed.

Comparative and functional genome analysis of fungi for development of the protein production host Trichoderma reesei

Filamentous fungi of the subphylum Pezizomycotina are well known as protein and secondary metabolite producers. Various industries take advantage of these capabilities. However, the molecular biology of yeasts, i.e. Saccharomycotina and especially that of Saccharomyces cerevisiae, the baker's yeast, is much better known. In an effort to explain fungal phenotypes through their genotypes we have compared protein coding gene contents of Pezizomycotina and Saccharomycotina. Only biomass degradation and secondary metabolism related protein families seem to have expanded recently in Pezizomycotina. Of the protein families clearly diverged between Pezizomycotina and Saccharomycotina, those related to mitochondrial functions emerge as the most prominent. However, the primary metabolism as described in S. cerevisiae is largely conserved in all fungi. Apart from the known secondary metabolism, Pezizomycotina have pathways that could link secondary metabolism to primary metabolism and a wealth of undescribed enzymes. Previous studies of individual Pezizomycotina genomes have shown that regardless of the difference in production efficiency and diversity of secreted proteins, the content of the known secretion machinery genes in Pezizomycotina and Saccharomycotina appears very similar. Genome wide analysis of gene products is therefore needed to better understand the efficient secretion of Pezizomycotina. We have developed methods applicable to transcriptome analysis of non-sequenced organisms. TRAC (Transcriptional profiling with the aid of affinity capture) has been previously developed at VTT for fast, focused transcription analysis. We introduce a version of TRAC that allows more powerful signal amplification and multiplexing. We also present computational optimisations of transcriptome analysis of non-sequenced organism and TRAC analysis in general. Trichoderma reesei is one of the most commonly used Pezizomycotina in the protein production industry. In order to understand its secretion system better and find clues for improvement of its industrial performance, we have analysed its transcriptomic response to protein secretion stress conditions. In comparison to S. cerevisiae, the response of T. reesei appears different, but still impacts on the same cellular functions. We also discovered in T. reesei interesting similarities to mammalian protein secretion stress response. Together these findings highlight targets for more detailed studies.

Design, Development, Synthesis, and Docking Analysis of 2-substituted Triclosan Analogs as Inhibitors for Plasmodium falciparum Enoyl-ACP Reductase

A structure-based approach has been adopted to develop 2'substituted analogs of triclosan. The Cl at position 2' in ring B of triclosan was chemically substituted with other functional groups like NH2, NO2 and their inhibitory potencies against PfENR were determined. The binding energies of the 2' substituted analogs of triclosan for enoyl-acyl carrier protein reductase (ENR) of Plasmodium falciparum were determined using Autodock. Based on the autodock results, we synthesized the potential compounds. The IC50 and inhibition constant (K-i) of 2' substituted analogs of triclosan were determined against purified PfENR. Among them, two compounds,2-(2'-Amino-4'-chloro-phenoxy)-5-chloro-phenol (compound 4) and 5-chloro-2-(4'-chloro-2'-nitro-phenoxy)-phenol) (compound 5) exhibited good potencies. Compound 4 followed uncompetitive inhibition kinetics with crotonoyl CoA and competitive with NADH. It was shown to have an IC50 of 110 nM; inhibition constant was 104 nM with the substrate and 61 nM with the cofactor. IC50 Of compound 5 was determined to be 229 nM. Compounds 4 and 5 showed significant inhibition of the parasite growth in P. falciparum culture. (C) 2009 IUBMB IUBMB Life, 61(11):1083-1091, 2009.

Convergence analysis of the Newton algorithm and a pseudo-time marching scheme for diffuse correlation tomography

We propose a self-regularized pseudo-time marching scheme to solve the ill-posed, nonlinear inverse problem associated with diffuse propagation of coherent light in a tissuelike object. In particular, in the context of diffuse correlation tomography (DCT), we consider the recovery of mechanical property distributions from partial and noisy boundary measurements of light intensity autocorrelation. We prove the existence of a minimizer for the Newton algorithm after establishing the existence of weak solutions for the forward equation of light amplitude autocorrelation and its Frechet derivative and adjoint. The asymptotic stability of the solution of the ordinary differential equation obtained through the introduction of the pseudo-time is also analyzed. We show that the asymptotic solution obtained through the pseudo-time marching converges to that optimal solution provided the Hessian of the forward equation is positive definite in the neighborhood of optimal solution. The superior noise tolerance and regularization-insensitive nature of pseudo-dynamic strategy are proved through numerical simulations in the context of both DCT and diffuse optical tomography. (C) 2010 Optical Society of America.

Struggling over subjectivity: A discursive analysis of strategic development in a group

We have seen growing interest in discursive perspectives on strategy. This perspective holds great promise for development of an understanding on how strategy discourse and subjectivity are intertwined. We wish to add to this existing research by outlining a discursive struggle approach to subjectivity. To understand the complex subjectification and empowering/disempowering effects of organizational strategy discourse, this approach focuses on organization-specific discourse mobilizations an various ways of resistance. Drawing on an analysis of the discourses and practices of ‘strategic development��� in an engineering and consulting group we provide an empirical illustration of such struggles over subjectivity. In particular, we report three examples of competing ways of making sense of and giving sense to strategic development, with specific subjectification tendencies. First, we show how corporate management can mobilize and appropriate a specific kind of discourse to attempt to gain control of the organization, which tends to reproduce managerial hegemony, but also trigger discursive and other forms of resistance. Second, we will illustrate how middle managers resist this hegemony by initiating a strategy discourse of their own to create room for manoeuvre in controversial situations. Third, we show how project engineers can distance themselves from managerial-initiated strategy discourses to maintain a viable identity despite all kinds of pressures. Although our examples are case-specific, we believe that similar discursive dynamics also characterize strategizing in other organizations.

Development of a New Finite Element for the Analysis of Sandwich Beams with Soft Core

A new super convergent sandwich beam finite element formulation is presented in this article. This element is a two-nodded, six degrees of freedom (dof) per node (3 dof u(0), w, phi for top and bottom face sheets each), which assumes that all the axial and flexural loads are taken by face sheets, while the core takes only the shear loads. The beam element is formulated based on first-order shear deformation theory for the face sheets and the core displacements are assumed to vary linearly across the thickness. A number of numerical experiments involving static, free vibration, and wave propagation analysis examples are solved with an aim to show the super convergent property of the formulated element. The examples presented in this article consider both metallic and composite face sheets. The formulated element is verified in most cases with the results available in the published literature.