3CAPS – a structural AP-site analogue as a tool to investigate DNA base excision repair

Abasic sites (AP-sites) are frequent DNA lesions, arising by spontaneous base hydrolysis or as intermediates of base excision repair (BER). The hemiacetal at the anomeric centre renders them chemically reactive, which presents a challenge to biochemical and structural investigation. Chemically more stable AP-site analogues have been used to avoid spontaneous decay, but these do not fully recapitulate the features of natural AP-sites. With its 3′-phosphate replaced by methylene, the abasic site analogue 3CAPS was suggested to circumvent some of these limitations. Here, we evaluated the properties of 3CAPS in biochemical BER assays with mammalian proteins. 3CAPS-containing DNA substrates were processed by APE1, albeit with comparably poor efficiency. APE1-cleaved 3CAPS can be extended by DNA polymerase β but repaired only by strand displacement as the 5′-deoxyribophosphate (dRP) cannot be removed. DNA glycosylases physically and functionally interact with 3CAPS substrates, underlining its structural integrity and biochemical reactivity. The AP lyase activity of bifunctional DNA glycosylases (NTH1, NEIL1, FPG), however, was fully inhibited. Notably, 3CAPS-containing DNA also effectively inhibited the activity of bifunctional glycosylases on authentic substrates. Hence, the chemically stable 3CAPS with its preserved hemiacetal functionality is a potent tool for BER research and a potential inhibitor of bifunctional DNA glycosylases.

OPPL-Galaxy, a Galaxy tool for enhancing ontology exploitation as part of bioinformatics workflows

Biomedical ontologies are key elements for building up the Life Sciences Semantic Web. Reusing and building biomedical ontologies requires flexible and versatile tools to manipulate them efficiently, in particular for enriching their axiomatic content. The Ontology Pre Processor Language (OPPL) is an OWL-based language for automating the changes to be performed in an ontology. OPPL augments the ontologists’ toolbox by providing a more efficient, and less error-prone, mechanism for enriching a biomedical ontology than that obtained by a manual treatment. Results We present OPPL-Galaxy, a wrapper for using OPPL within Galaxy. The functionality delivered by OPPL (i.e. automated ontology manipulation) can be combined with the tools and workflows devised within the Galaxy framework, resulting in an enhancement of OPPL. Use cases are provided in order to demonstrate OPPL-Galaxy’s capability for enriching, modifying and querying biomedical ontologies. Conclusions Coupling OPPL-Galaxy with other bioinformatics tools of the Galaxy framework results in a system that is more than the sum of its parts. OPPL-Galaxy opens a new dimension of analyses and exploitation of biomedical ontologies, including automated reasoning, paving the way towards advanced biological data analyses.

Valuing transferred machine tool technology:Relating value to product attributes and preferences of acquirers

The value of technology and the appropriate form of transfer arrangement are important questions to be resolved when transferring technology between Western manufacturing firms and partners in industrialising and developing countries. This article reports on surveys carried out in the machine tool industries in the UK and China to establish the differences and similarities between owners and acquirers of technology regarding the relative importance of the factors they evaluate, and the assessments they make, when considering a technology transfer. It also outlines the development of a framework for technology valuation. The survey results indicate that the value of product technology is related to superior technical performance, especially on reliability and functionality, and the prospects of premium prices and increased sales of the technology transfer based machine tools. Access to markets is the main objective of UK companies, while Chinese companies are concerned about improving their technological capability. There are significant risks, especially related to performance in the market, and while owners and acquirers have benefited in the short term, the long term collaboration required for strategic benefits has been difficult to achieve because of the different priorities of the owners and the acquirers.

Designing multiple user perspectives and functionality for clinical decision support systems

Clinical Decision Support Systems (CDSSs) need to disseminate expertise in formats that suit different end users and with functionality tuned to the context of assessment. This paper reports research into a method for designing and implementing knowledge structures that facilitate the required flexibility. A psychological model of expertise is represented using a series of formally specified and linked XML trees that capture increasing elements of the model, starting with hierarchical structuring, incorporating reasoning with uncertainty, and ending with delivering the final CDSS. The method was applied to the Galatean Risk and Safety Tool, GRiST, which is a web-based clinical decision support system (www.egrist.org) for assessing mental-health risks. Results of its clinical implementation demonstrate that the method can produce a system that is able to deliver expertise targetted and formatted for specific patient groups, different clinical disciplines, and alternative assessment settings. The approach may be useful for developing other real-world systems using human expertise and is currently being applied to a logistics domain. © 2013 Polish Information Processing Society.

GEO Label – quality information interrogation tool for geospatial datasets:towards effective visualization of quality metadata

Although the importance of dataset fitness-for-use evaluation and intercomparison is widely recognised within the GIS community, no practical tools have yet been developed to support such interrogation. GeoViQua aims to develop a GEO label which will visually summarise and allow interrogation of key informational aspects of geospatial datasets upon which users rely when selecting datasets for use. The proposed GEO label will be integrated in the Global Earth Observation System of Systems (GEOSS) and will be used as a value and trust indicator for datasets accessible through the GEO Portal. As envisioned, the GEO label will act as a decision support mechanism for dataset selection and thereby hopefully improve user recognition of the quality of datasets. To date we have conducted 3 user studies to (1) identify the informational aspects of geospatial datasets upon which users rely when assessing dataset quality and trustworthiness, (2) elicit initial user views on a GEO label and its potential role and (3), evaluate prototype label visualisations. Our first study revealed that, when evaluating quality of data, users consider 8 facets: dataset producer information; producer comments on dataset quality; dataset compliance with international standards; community advice; dataset ratings; links to dataset citations; expert value judgements; and quantitative quality information. Our second study confirmed the relevance of these facets in terms of the community-perceived function that a GEO label should fulfil: users and producers of geospatial data supported the concept of a GEO label that provides a drill-down interrogation facility covering all 8 informational aspects. Consequently, we developed three prototype label visualisations and evaluated their comparative effectiveness and user preference via a third user study to arrive at a final graphical GEO label representation. When integrated in the GEOSS, an individual GEO label will be provided for each dataset in the GEOSS clearinghouse (or other data portals and clearinghouses) based on its available quality information. Producer and feedback metadata documents are being used to dynamically assess information availability and generate the GEO labels. The producer metadata document can either be a standard ISO compliant metadata record supplied with the dataset, or an extended version of a GeoViQua-derived metadata record, and is used to assess the availability of a producer profile, producer comments, compliance with standards, citations and quantitative quality information. GeoViQua is also currently developing a feedback server to collect and encode (as metadata records) user and producer feedback on datasets; these metadata records will be used to assess the availability of user comments, ratings, expert reviews and user-supplied citations for a dataset. The GEO label will provide drill-down functionality which will allow a user to navigate to a GEO label page offering detailed quality information for its associated dataset. At this stage, we are developing the GEO label service that will be used to provide GEO labels on demand based on supplied metadata records. In this presentation, we will provide a comprehensive overview of the GEO label development process, with specific emphasis on the GEO label implementation and integration into the GEOSS.

Selecting the 'invisible' user interface development tool

Developers of interactive software are confronted by an increasing variety of software tools to help engineer the interactive aspects of software applications. Typically resorting to ad hoc means of tool selection, developers are often dissatisfied with their chosen tool on account of the fact that the tool lacks required functionality or does not fit seamlessly within the context in which it is to be used. This paper describes a system for evaluating the suitability of user interface development tools for use in software development organisations and projects such that the selected tool appears ‘invisible’ within its anticipated context of use. The paper also outlines and presents the results of an informal empirical study and a series of observational case studies of the system.

Investigating mental health risk assessment in primary care and the potential role of a structured decision support tool, GRiST

Aim: To explore current risk assessment processes in general practice and Improving Access to Psychological Therapies (IAPT) services, and to consider whether the Galatean Risk and Safety Tool (GRiST) can help support improved patient care. Background: Much has been written about risk assessment practice in secondary mental health care, but little is known about how it is undertaken at the beginning of patients' care pathways, within general practice and IAPT services. Methods: Interviews with eight general practice and eight IAPT clinicians from two primary care trusts in the West Midlands, UK, and eight service users from the same region. Interviews explored current practice and participants' views and experiences of mental health risk assessment. Two focus groups were also carried out, one with general practice and one with IAPT clinicians, to review interview findings and to elicit views about GRiST from a demonstration of its functionality. Data were analysed using thematic analysis. Findings Variable approaches to mental health risk assessment were observed. Clinicians were anxious that important risk information was being missed, and risk communication was undermined. Patients felt uninvolved in the process, and both clinicians and patients expressed anxiety about risk assessment skills. Clinicians were positive about the potential for GRiST to provide solutions to these problems. Conclusions: A more structured and systematic approach to risk assessment in general practice and IAPT services is needed, to ensure important risk information is captured and communicated across the care pathway. GRiST has the functionality to support this aspect of practice.

A Log Tool for Software Systems Analyses

The article presents a new type of logs merging tool for multiple blade telecommunication systems based on the development of a new approach. The introduction of the new logs merging tool (the Log Merger) can help engineers to build a processes behavior timeline with a flexible system of information structuring used to assess the changes in the analyzed system. This logs merging system based on the experts experience and their analytical skills generates a knowledge base which could be advantageous in further decision-making expert system development. This paper proposes and discusses the design and implementation of the Log Merger, its architecture, multi-board analysis of capability and application areas. The paper also presents possible ways of further tool improvement e.g. - to extend its functionality and cover additional system platforms. The possibility to add an analysis module for further expert system development is also considered.

Enterprise Collaboration Framework for Managing, Advancing and Unifying the Functionality of Multiple Cloud-Based Services with the Help of a Graph API

Part 5: Service Orientation in Collaborative Networks

Hyperlinks in e-books : expanding the functionality of end-notes

With its powerful search engines and billions of published pages, the Worldwide Web has become the ultimate tool to explore the human experience. But, despite the advent of the digital revolution, e-books, at their core, have remained remarkably similar to their printed siblings. This has resulted in a clear dichotomy between two ways of reading: on one side, the multi-dimensional world of the Web; on the other, the linearity of books and e-books. My investigation of the literature indicates that the focus of attempts to merge these two modes of production, and hence of reading, has been the insertion of interactivity into fiction. As I will show in the Literature Review, a clear thrust of research since the early 1990s, and in my opinion the most significant, has concentrated on presenting the reader with choices that affect the plot. This has resulted in interactive stories in which the structure of the narrative can be altered by the reader of experimental fiction. The interest in this area of research is not surprising, as the interaction of readers with the fabric of the narrative provides a fertile ground for exploring, analysing, and discussing issues of plot consistency and continuity. I found in the literature several papers concerned with the effects of hyperlinking on literature, but none about how hyperlinked material and narrative could be integrated without compromising the narrative flow as designed by the author. It led me to think that the researchers had accepted hypertextuality and the linear organisation of fiction as being antithetical, thereby ignoring the possibility of exploiting the first while preserving the second. All the works I consulted were focussed on exploring the possibilities provided to authors (and readers) by hypertext or how hypertext literature affects literary criticism. This was true in earlier works by Landow and Harpold and remained true in later works by Bolter and Grusin. To quote another example, in his book Hypertext 3.0, Landow states: “Most who have speculated on the relation between hypertextuality and fiction concentrate [...] on the effects it will have on linear narrative”, and “hypertext opens major questions about story and plot by apparently doing away with linear organization” (Landow, 2006, pp. 220, 221). In other words, the authors have added narrative elements to Web pages, effectively placing their stories in a subordinate role. By focussing on “opening up” the plots, the researchers have missed the opportunity to maintain the integrity of their stories and use hyperlinked information to provide interactive access to backstory and factual bases. This would represent a missing link between the traditional way of reading, in which the readers have no influence on the path the author has laid out for them, and interactive narrative, in which the readers choose their way across alternatives, thereby, at least to a certain extent, creating their own path. It would be, to continue the metaphor, as if the readers could follow the main path created by the author while being able to get “sidetracked” into exploring hyperlinked material. In Hypertext 3.0, Landow refers to an “Axial structure [of hypertext] characteristic of electronic books and scholarly books with foot-and endnotes” versus a “Network structure of hypertext” (Landow, 2006, p. 70). My research aims at generalising the axial structure and extending it to fiction without losing the linearity at its core. In creative nonfiction, the introduction of places, scenes, and settings, together with characterisation, brings to life the facts without altering them; while much fiction draws on facts to provide a foundation, or narrative elements, for the work. But how can the reader distinguish between facts and representations? For example, to what extent do dialogues and perceptions present what was actually said and thought? Some authors of creative nonfiction use end-notes to provide comments and citations while minimising disruption the flow of the main text, but they are limited in scope and constrained in space. Each reader should be able to enjoy the narrative as if it were a novel but also to explore the facts at the level of detail s/he needs. For this to be possible, end-notes should provide a Web-like way of exploring in more detail what the author has already researched. My research aims to develop ways of integrating narrative prose and hyperlinked documents into a Hyperbook. Its goal is to create a new writing paradigm in which a story incorporates a gateway to detailed information. While creative nonfiction uses the techniques of fictional writing to provide reportage of actual events and fact-based fiction illuminates the affectual dimensions of what happened (e.g., Kate Grenville’s The Secret River and Hilary Mantel’s Wolf Hall), Hyperbooks go one step further and link narrative prose to the details of the events on which the narrative is based or, more in general, to information the reader might find of interest. My dissertation introduces and utilises Hyperbooks to engage in two parallel types of investigation Build knowledge about Italian WWII POWs held in Australia and present it as part of a novella in Hyperbook format. Develop a new piece of technology capable of extending the writing and reading process.

Sim-xl: A Powerful And User-friendly Tool For Peptide Cross-linking Analysis.

Chemical cross-linking has emerged as a powerful approach for the structural characterization of proteins and protein complexes. However, the correct identification of covalently linked (cross-linked or XL) peptides analyzed by tandem mass spectrometry is still an open challenge. Here we present SIM-XL, a software tool that can analyze data generated through commonly used cross-linkers (e.g., BS3/DSS). Our software introduces a new paradigm for search-space reduction, which ultimately accounts for its increase in speed and sensitivity. Moreover, our search engine is the first to capitalize on reporter ions for selecting tandem mass spectra derived from cross-linked peptides. It also makes available a 2D interaction map and a spectrum-annotation tool unmatched by any of its kind. We show SIM-XL to be more sensitive and faster than a competing tool when analyzing a data set obtained from the human HSP90. The software is freely available for academic use at http://patternlabforproteomics.org/sim-xl. A video demonstrating the tool is available at http://patternlabforproteomics.org/sim-xl/video. SIM-XL is the first tool to support XL data in the mzIdentML format; all data are thus available from the ProteomeXchange consortium (identifier PXD001677).

Capillary electrophoresis (CE): a powerful tool to characterize humic acid (HA)

The present study evaluates the possibility of eliminating the purification steps involved in the characterization of HA by capillary zone electrophoresis (CZE). The HAs of various sources were analyzed, showing different electropherograms by CZE, which depend on the charge and size of HA. The data suggest that the purification of the sample is not necessary to characterize HAs. Based on the results, CZE showed to be a promising tool to characterize HA of different origins without the purification step of the sample.

Catalytic enantioselective arylations: boron to zinc exchange as a powerful tool for the generation of transferable aryl groups

The transmetalation between boron and zinc is of great importance for application in organic synthesis, since it allows the formation of new carbon-carbon bonds between organometallic units and electrophiles. The direct arylation of aldehydes or more scarcely ketones, in a catalytic, enantioselective manner using chiral catalysts has been described recently. The enantiomerically enriched diarylmethanols obtained in these reactions are valuable precursors for important bioactive molecules. This review provides a synopsis of this ever-growing field and highlights some of the challenges that still remain.

Ratio of weight to height gain: a useful tool for identifying children at risk of becoming overweight or obese at preschool age

PURPOSE: To analyze the usefulness of the weight gain/height gain ratio from birth to two and three years of age as a predictive risk indicator of excess weight at preschool age. METHODS: The weight and height/length of 409 preschool children at daycare centers were measured according to internationally recommended rules. The weight values and body mass indices of the children were transformed into a z-score per the standard method described by the World Health Organization. The Pearson correlation coefficients (rP) and the linear regressions between the anthropometric parameters and the body mass index z-scores of preschool children were statistically analyzed (alpha = 0.05). RESULTS: The mean age of the study population was 3.2 years (± 0.3 years). The prevalence of excess weight was 28.8%, and the prevalence of overweight and obesity was 8.8%. The correlation coefficients between the body mass index z-scores of the preschool children and the birth weights or body mass indices at birth were low (0.09 and 0.10, respectively). There was a high correlation coefficient (rP = 0.79) between the mean monthly gain of weight and the body mass index z-score of preschool children. A higher coefficient (rP = 0.93) was observed between the ratio of the mean weight gain per height gain (g/cm) and the preschool children body mass index z-score. The coefficients and their differences were statistically significant. CONCLUSION: Regardless of weight or length at birth, the mean ratio between the weight gain per g/cm of height growth from birth presented a strong correlation with the body mass index of preschool children. These results suggest that this ratio may be a good indicator of the risk of excess weight and obesity in preschool-aged children.

Flow cytometry as a tool in the evaluation of blood leukocyte function in Chelonia mydas (Linnaeus, 1758) (Testudines, Cheloniidae)

Chelonia mydas is a sea turtle that feeds and nests on the Brazilian coast and a disease called fibropapillomatosis is a threat to this species. Because of this, it is extremely necessary to determine a methodology that would enable the analysis of blood leukocyte function in these sea turtles. In order to achieve this aim, blood samples were collected from C. mydas with or without fibropapillomas captured on the São Paulo north coast. Blood samples were placed in tubes containing sodium heparin and were transported under refrigeration to the laboratory in sterile RPMI 1640 cell culture medium. Leukocytes were separated by density gradient using Ficoll-PaqueTM Plus, Amershan Biociences®. The following stimuli were applied in the assessment of leukocyte function: Phorbol Miristate-Acetate (PMA) for oxidative burst activity evaluation and Zymosan A (Saccharomyces cerevisiae) Bio Particles®, Alexa Fluor® 594 conjugate for phagocytosis evaluation. Three cell populations were identified: heterophils, monocytes and lymphocytes. Monocytes were the cells responsible for phagocytosis and oxidative burst.