WorldWideScience

Sample records for link discovery techniques

  1. Performance Evaluation of Frequent Subgraph Discovery Techniques

    Saif Ur Rehman

    2014-01-01

    Full Text Available Due to rapid development of the Internet technology and new scientific advances, the number of applications that model the data as graphs increases, because graphs have highly expressive power to model a complicated structure. Graph mining is a well-explored area of research which is gaining popularity in the data mining community. A graph is a general model to represent data and has been used in many domains such as cheminformatics, web information management system, computer network, and bioinformatics, to name a few. In graph mining the frequent subgraph discovery is a challenging task. Frequent subgraph mining is concerned with discovery of those subgraphs from graph dataset which have frequent or multiple instances within the given graph dataset. In the literature a large number of frequent subgraph mining algorithms have been proposed; these included FSG, AGM, gSpan, CloseGraph, SPIN, Gaston, and Mofa. The objective of this research work is to perform quantitative comparison of the above listed techniques. The performances of these techniques have been evaluated through a number of experiments based on three different state-of-the-art graph datasets. This novel work will provide base for anyone who is working to design a new frequent subgraph discovery technique.

  2. A Technique Socratic Questioning-Guided Discovery

    M. Hakan Türkçapar

    2012-03-01

    Full Text Available “Socratic Method” is a way of teaching philosophical thinking and knowledge by asking questions which was used by antique period greek philosopher Socrates. Socrates was teaching knowledge to his followers by asking questions and the conversation between them was named “Socratic Dialogues”. In this meaning, no novel knowledge is taught to the individual but only what is formerly known is reminded and rediscovered. The form of socratic questioning which is used during the process of cognitive behavioral therapy is known as Guided Discovery. In this method it is aimed to make the client notice the piece of knowledge which he could notice but is not aware with a series of questions. Socratic method or guided discovery consists of several steps which are: Identifying the problem by listening to the client and making reflections, finding alternatives by examining and evaluating, reidentification by using the newly found information and questioning the old distorted belief and reaching to a conclusion and applying it. Question types used during these procedures are, questions for gaining information, questions revealing the meanings, questions revealing the beliefs, questions about behaviours during the similar past experiences, analyse questions and analytic synthesis questions. In order to make the patient feel understood it is important to be empathetic and summarising the problem during the interview. In this text, steps of Socratic Questioning-Guided Discovery will be reviewed with sample dialogues after each step

  3. SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines

    Yumusak, Semih; Dogdu, Erdogan; Kodaz, Halife; Kamilaris, Andreas

    2016-01-01

    In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this ...

  4. Enhancing Big Data Value Using Knowledge Discovery Techniques

    Mai Abdrabo; Mohammed Elmogy; Ghada Eltaweel; Sherif Barakat

    2016-01-01

    The world has been drowned by floods of data due to technological development. Consequently, the Big Data term has gotten the expression to portray the gigantic sum. Different sorts of quick data are doubling every second. We have to profit from this enormous surge of data to convert it to knowledge. Knowledge Discovery (KDD) can enhance detecting the value of Big Data based on some techniques and technologies like Hadoop, MapReduce, and NoSQL. The use of Big D...

  5. Privacy-aware knowledge discovery novel applications and new techniques

    Bonchi, Francesco

    2010-01-01

    Covering research at the frontier of this field, Privacy-Aware Knowledge Discovery: Novel Applications and New Techniques presents state-of-the-art privacy-preserving data mining techniques for application domains, such as medicine and social networks, that face the increasing heterogeneity and complexity of new forms of data. Renowned authorities from prominent organizations not only cover well-established results-they also explore complex domains where privacy issues are generally clear and well defined, but the solutions are still preliminary and in continuous development. Divided into seve

  6. Discovery – The Link to H.Pylori Bacteria

    NCI supported research to solidify the link between H. pylori infections and stomach cancer. As a result, new cancer treatment and prevention strategies are being developed, encouraging scientists to carefully examine other cancers for viral and bacterial connections.

  7. Measuring Journal Linking Success from a Discovery Service

    Kenyon Stuart

    2015-03-01

    Full Text Available Online linking to full text via third-party link-resolution services, such as Serials Solutions 360 Link or Ex Libris’ SFX, has become a popular method of access to users in academic libraries. This article describes several attempts made over the course of the past three years at the University of Michigan to gather data on linkage failure: the method used, the limiting factors, the changes made in methods, an analysis of the data collected, and a report of steps taken locally because of the studies. It is hoped that the experiences at one institution may be applicable more broadly and, perhaps, produce a stronger data-driven effort at improving linking services.

  8. Machine-learning techniques applied to antibacterial drug discovery.

    Durrant, Jacob D; Amaro, Rommie E

    2015-01-01

    The emergence of drug-resistant bacteria threatens to revert humanity back to the preantibiotic era. Even now, multidrug-resistant bacterial infections annually result in millions of hospital days, billions in healthcare costs, and, most importantly, tens of thousands of lives lost. As many pharmaceutical companies have abandoned antibiotic development in search of more lucrative therapeutics, academic researchers are uniquely positioned to fill the pipeline. Traditional high-throughput screens and lead-optimization efforts are expensive and labor intensive. Computer-aided drug-discovery techniques, which are cheaper and faster, can accelerate the identification of novel antibiotics, leading to improved hit rates and faster transitions to preclinical and clinical testing. The current review describes two machine-learning techniques, neural networks and decision trees, that have been used to identify experimentally validated antibiotics. We conclude by describing the future directions of this exciting field. © 2015 John Wiley & Sons A/S.

  9. An intelligent content discovery technique for health portal content management.

    De Silva, Daswin; Burstein, Frada

    2014-04-23

    Continuous content management of health information portals is a feature vital for its sustainability and widespread acceptance. Knowledge and experience of a domain expert is essential for content management in the health domain. The rate of generation of online health resources is exponential and thereby manual examination for relevance to a specific topic and audience is a formidable challenge for domain experts. Intelligent content discovery for effective content management is a less researched topic. An existing expert-endorsed content repository can provide the necessary leverage to automatically identify relevant resources and evaluate qualitative metrics. This paper reports on the design research towards an intelligent technique for automated content discovery and ranking for health information portals. The proposed technique aims to improve efficiency of the current mostly manual process of portal content management by utilising an existing expert-endorsed content repository as a supporting base and a benchmark to evaluate the suitability of new content A model for content management was established based on a field study of potential users. The proposed technique is integral to this content management model and executes in several phases (ie, query construction, content search, text analytics and fuzzy multi-criteria ranking). The construction of multi-dimensional search queries with input from Wordnet, the use of multi-word and single-word terms as representative semantics for text analytics and the use of fuzzy multi-criteria ranking for subjective evaluation of quality metrics are original contributions reported in this paper. The feasibility of the proposed technique was examined with experiments conducted on an actual health information portal, the BCKOnline portal. Both intermediary and final results generated by the technique are presented in the paper and these help to establish benefits of the technique and its contribution towards effective

  10. SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines

    Yumusak, Semih; Dogdu, Erdogan; Kodaz, Halife; Kamilaris, Andreas; Vandenbussche, Pierre-Yves

    In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this method, most of the currently listed SPARQL endpoints in existing endpoint repositories, as well as a significant number of new SPARQL endpoints, have been discovered. Finally, we have developed a new SPARQL endpoint crawler (SpEC) for crawling and link analysis.

  11. Integration and analysis of neighbor discovery and link quality estimation in wireless sensor networks.

    Radi, Marjan; Dezfouli, Behnam; Abu Bakar, Kamalrulnizam; Abd Razak, Shukor

    2014-01-01

    Network connectivity and link quality information are the fundamental requirements of wireless sensor network protocols to perform their desired functionality. Most of the existing discovery protocols have only focused on the neighbor discovery problem, while a few number of them provide an integrated neighbor search and link estimation. As these protocols require a careful parameter adjustment before network deployment, they cannot provide scalable and accurate network initialization in large-scale dense wireless sensor networks with random topology. Furthermore, performance of these protocols has not entirely been evaluated yet. In this paper, we perform a comprehensive simulation study on the efficiency of employing adaptive protocols compared to the existing nonadaptive protocols for initializing sensor networks with random topology. In this regard, we propose adaptive network initialization protocols which integrate the initial neighbor discovery with link quality estimation process to initialize large-scale dense wireless sensor networks without requiring any parameter adjustment before network deployment. To the best of our knowledge, this work is the first attempt to provide a detailed simulation study on the performance of integrated neighbor discovery and link quality estimation protocols for initializing sensor networks. This study can help system designers to determine the most appropriate approach for different applications.

  12. Integration and Analysis of Neighbor Discovery and Link Quality Estimation in Wireless Sensor Networks

    Marjan Radi

    2014-01-01

    Full Text Available Network connectivity and link quality information are the fundamental requirements of wireless sensor network protocols to perform their desired functionality. Most of the existing discovery protocols have only focused on the neighbor discovery problem, while a few number of them provide an integrated neighbor search and link estimation. As these protocols require a careful parameter adjustment before network deployment, they cannot provide scalable and accurate network initialization in large-scale dense wireless sensor networks with random topology. Furthermore, performance of these protocols has not entirely been evaluated yet. In this paper, we perform a comprehensive simulation study on the efficiency of employing adaptive protocols compared to the existing nonadaptive protocols for initializing sensor networks with random topology. In this regard, we propose adaptive network initialization protocols which integrate the initial neighbor discovery with link quality estimation process to initialize large-scale dense wireless sensor networks without requiring any parameter adjustment before network deployment. To the best of our knowledge, this work is the first attempt to provide a detailed simulation study on the performance of integrated neighbor discovery and link quality estimation protocols for initializing sensor networks. This study can help system designers to determine the most appropriate approach for different applications.

  13. Developing and Implementing an Assessment Technique to Measure Linked Concepts

    Ye, Li; Oueini, Razanne; Lewis, Scott E.

    2015-01-01

    The links students make among chemistry content is considered essential for a robust, enduring understanding in multiple learning theories. This article describes the development and implementation of an assessment technique, termed a Measure of Linked Concepts, designed to inform instructors on students' understanding of linking content…

  14. Semantic Service Discovery Techniques for the composable web

    Fernández Villamor, José Ignacio

    2013-01-01

    This PhD thesis contributes to the problem of resource and service discovery in the context of the composable web. In the current web, mashup technologies allow developers reusing services and contents to build new web applications. However, developers face a problem of information flood when searching for appropriate services or resources for their combination. To contribute to overcoming this problem, a framework is defined for the discovery of services and resources. In this framework, thr...

  15. When fragments link : a bibliometric perspective on the development of fragment-based drug discovery

    Romasanta, A.K.S.; van der Sijde, P.C.; Hellsten, I.; Hubbard, Roderick E.; Keseru, Gyorgy M.; van Muijlwijk-Koezen, Jacqueline E.; de Esch, I.J.P.

    2018-01-01

    Fragment-based drug discovery (FBDD) is a highly interdisciplinary field, rich in ideas integrated from pharmaceutical sciences, chemistry, biology, and physics, among others. To enrich our understanding of the development of the field, we used bibliometric techniques to analyze 3642 publications in

  16. Symmetric Link Key Management for Secure Neighbor Discovery in a Decentralized Wireless Sensor Network

    2017-09-01

    KEY MANAGEMENT FOR SECURE NEIGHBOR DISCOVERY IN A DECENTRALIZED WIRELESS SENSOR NETWORK by Kelvin T. Chew September 2017 Thesis Advisor...and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188) Washington, DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. REPORT...DATE September 2017 3. REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE SYMMETRIC LINK KEY MANAGEMENT FOR SECURE NEIGHBOR

  17. Leveraging Crowdsourcing and Linked Open Data for Geoscience Data Sharing and Discovery

    Narock, T. W.; Rozell, E. A.; Hitzler, P.; Arko, R. A.; Chandler, C. L.; Wilson, B. D.

    2013-12-01

    Data citation standards can form the basis for increased incentives, recognition, and rewards for scientists. Additionally, knowing which data were utilized in a particular publication can enhance discovery and reuse. Yet, a lack of data citation information in existing publications as well as ambiguities across datasets can limit the accuracy of automated linking approaches. We describe a crowdsourcing approach, based on Linked Open Data, in which AGU abstracts are linked to the data used in those presentations. We discuss our efforts to incentivize participants through promotion of their research, the role that the Semantic Web can play in this effort, and how this work differs from existing platforms such as Mendeley and ResearchGate. Further, we discuss the benefits and challenges of Linked Open Data as a technical solution including the role of provenance, trust, and computational reasoning.

  18. SEMANTIC WEB SERVICES – DISCOVERY, SELECTION AND COMPOSITION TECHNIQUES

    Sowmya Kamath S; Ananthanarayana V.S

    2013-01-01

    Web services are already one of the most important resources on the Internet. As an integrated solution for realizing the vision of the Next Generation Web, semantic web services combine semantic web technology with web service technology, envisioning automated life cycle management of web services. This paper discusses the significance and importance of service discovery & selection to business logic, and the requisite current research in the various phases of the semantic web...

  19. Publication, discovery and interoperability of Clinical Decision Support Systems: A Linked Data approach.

    Marco-Ruiz, Luis; Pedrinaci, Carlos; Maldonado, J A; Panziera, Luca; Chen, Rong; Bellika, J Gustav

    2016-08-01

    The high costs involved in the development of Clinical Decision Support Systems (CDSS) make it necessary to share their functionality across different systems and organizations. Service Oriented Architectures (SOA) have been proposed to allow reusing CDSS by encapsulating them in a Web service. However, strong barriers in sharing CDS functionality are still present as a consequence of lack of expressiveness of services' interfaces. Linked Services are the evolution of the Semantic Web Services paradigm to process Linked Data. They aim to provide semantic descriptions over SOA implementations to overcome the limitations derived from the syntactic nature of Web services technologies. To facilitate the publication, discovery and interoperability of CDS services by evolving them into Linked Services that expose their interfaces as Linked Data. We developed methods and models to enhance CDS SOA as Linked Services that define a rich semantic layer based on machine interpretable ontologies that powers their interoperability and reuse. These ontologies provided unambiguous descriptions of CDS services properties to expose them to the Web of Data. We developed models compliant with Linked Data principles to create a semantic representation of the components that compose CDS services. To evaluate our approach we implemented a set of CDS Linked Services using a Web service definition ontology. The definitions of Web services were linked to the models developed in order to attach unambiguous semantics to the service components. All models were bound to SNOMED-CT and public ontologies (e.g. Dublin Core) in order to count on a lingua franca to explore them. Discovery and analysis of CDS services based on machine interpretable models was performed reasoning over the ontologies built. Linked Services can be used effectively to expose CDS services to the Web of Data by building on current CDS standards. This allows building shared Linked Knowledge Bases to provide machine

  20. A Framework for Automatic Web Service Discovery Based on Semantics and NLP Techniques

    Asma Adala

    2011-01-01

    Full Text Available As a greater number of Web Services are made available today, automatic discovery is recognized as an important task. To promote the automation of service discovery, different semantic languages have been created that allow describing the functionality of services in a machine interpretable form using Semantic Web technologies. The problem is that users do not have intimate knowledge about semantic Web service languages and related toolkits. In this paper, we propose a discovery framework that enables semantic Web service discovery based on keywords written in natural language. We describe a novel approach for automatic discovery of semantic Web services which employs Natural Language Processing techniques to match a user request, expressed in natural language, with a semantic Web service description. Additionally, we present an efficient semantic matching technique to compute the semantic distance between ontological concepts.

  1. A Linked Science Investigation: Enhancing Climate Change Data Discovery with Semantic Technologies.

    Pouchard, Line C; Branstetter, Marcia L; Cook, Robert B; Devarakonda, Ranjeet; Green, Jim; Palanisamy, Giri; Alexander, Paul; Noy, Natalya F

    2013-09-01

    Linked Science is the practice of inter-connecting scientific assets by publishing, sharing and linking scientific data and processes in end-to-end loosely coupled workflows that allow the sharing and re-use of scientific data. Much of this data does not live in the cloud or on the Web, but rather in multi-institutional data centers that provide tools and add value through quality assurance, validation, curation, dissemination, and analysis of the data. In this paper, we make the case for the use of scientific scenarios in Linked Science. We propose a scenario in river-channel transport that requires biogeochemical experimental data and global climate-simulation model data from many sources. We focus on the use of ontologies-formal machine-readable descriptions of the domain-to facilitate search and discovery of this data. Mercury, developed at Oak Ridge National Laboratory, is a tool for distributed metadata harvesting, search and retrieval. Mercury currently provides uniform access to more than 100,000 metadata records; 30,000 scientists use it each month. We augmented search in Mercury with ontologies, such as the ontologies in the Semantic Web for Earth and Environmental Terminology (SWEET) collection by prototyping a component that provides access to the ontology terms from Mercury. We evaluate the coverage of SWEET for the ORNL Distributed Active Archive Center (ORNL DAAC).

  2. When fragments link: a bibliometric perspective on the development of fragment-based drug discovery.

    Romasanta, Angelo K S; van der Sijde, Peter; Hellsten, Iina; Hubbard, Roderick E; Keseru, Gyorgy M; van Muijlwijk-Koezen, Jacqueline; de Esch, Iwan J P

    2018-05-05

    Fragment-based drug discovery (FBDD) is a highly interdisciplinary field, rich in ideas integrated from pharmaceutical sciences, chemistry, biology, and physics, among others. To enrich our understanding of the development of the field, we used bibliometric techniques to analyze 3642 publications in FBDD, complementing accounts by key practitioners. Mapping its core papers, we found the transfer of knowledge from academia to industry. Co-authorship analysis showed that university-industry collaboration has grown over time. Moreover, we show how ideas from other scientific disciplines have been integrated into the FBDD paradigm. Keyword analysis showed that the field is organized into four interconnected practices: library design, fragment screening, computational methods, and optimization. This study highlights the importance of interactions among various individuals and institutions from diverse disciplines in newly emerging scientific fields. Copyright © 2018. Published by Elsevier Ltd.

  3. Linking human factors to corporate strategy with cognitive mapping techniques.

    Village, Judy; Greig, Michael; Salustri, Filippo A; Neumann, W Patrick

    2012-01-01

    For human factors (HF) to avoid being considered of "side-car" status, it needs to be positioned within the organization in such a way that it affects business strategies and their implementation. Tools are needed to support this effort. This paper explores the feasibility of applying a technique from operational research called cognitive mapping to link HF to corporate strategy. Using a single case study, a cognitive map is drawn to reveal the complex relationships between human factors and achieving an organization's strategic goals. Analysis of the map for central concepts and reinforcing loops enhances understanding that can lead to discrete initiatives to facilitate integration of HF. It is recommended that this technique be used with senior managers to understand the organizations` strategic goals and enhance understanding of the potential for HF to contribute to the strategic goals.

  4. Melodic pattern discovery by structural analysis via wavelets and clustering techniques

    Velarde, Gissel; Meredith, David

    We present an automatic method to support melodic pattern discovery by structural analysis of symbolic representations by means of wavelet analysis and clustering techniques. In previous work, we used the method to recognize the parent works of melodic segments, or to classify tunes into tune......-means to cluster melodic segments into groups of measured similarity and obtain a raking of the most prototypical melodic segments or patterns and their occurrences. We test the method on the JKU Patterns Development Database and evaluate it based on the ground truth defined by the MIREX 2013 Discovery of Repeated...... Themes & Sections task. We compare the results of our method to the output of geometric approaches. Finally, we discuss about the relevance of our wavelet-based analysis in relation to structure, pattern discovery, similarity and variation, and comment about the considerations of the method when used...

  5. Contributions of computational chemistry and biophysical techniques to fragment-based drug discovery.

    Gozalbes, Rafael; Carbajo, Rodrigo J; Pineda-Lucena, Antonio

    2010-01-01

    In the last decade, fragment-based drug discovery (FBDD) has evolved from a novel approach in the search of new hits to a valuable alternative to the high-throughput screening (HTS) campaigns of many pharmaceutical companies. The increasing relevance of FBDD in the drug discovery universe has been concomitant with an implementation of the biophysical techniques used for the detection of weak inhibitors, e.g. NMR, X-ray crystallography or surface plasmon resonance (SPR). At the same time, computational approaches have also been progressively incorporated into the FBDD process and nowadays several computational tools are available. These stretch from the filtering of huge chemical databases in order to build fragment-focused libraries comprising compounds with adequate physicochemical properties, to more evolved models based on different in silico methods such as docking, pharmacophore modelling, QSAR and virtual screening. In this paper we will review the parallel evolution and complementarities of biophysical techniques and computational methods, providing some representative examples of drug discovery success stories by using FBDD.

  6. Tools, techniques, organisation and culture of the CADD group at Sygnature Discovery.

    St-Gallay, Steve A; Sambrook-Smith, Colin P

    2017-03-01

    Computer-aided drug design encompasses a wide variety of tools and techniques, and can be implemented with a range of organisational structures and focus in different organisations. Here we outline the computational chemistry skills within Sygnature Discovery, along with the software and hardware at our disposal, and briefly discuss the methods that are not employed and why. The goal of the group is to provide support for design and analysis in order to improve the quality of compounds synthesised and reduce the timelines of drug discovery projects, and we reveal how this is achieved at Sygnature. Impact on medicinal chemistry is vital to demonstrating the value of computational chemistry, and we discuss the approaches taken to influence the list of compounds for synthesis, and how we recognise success. Finally we touch on some of the areas being developed within the team in order to provide further value to the projects and clients.

  7. Linked Environments for Atmospheric Discovery (LEAD): A Cyberinfrastructure for Mesoscale Meteorology Research and Education

    Droegemeier, K.

    2004-12-01

    A new National Science Foundation Large Information Technology Research (ITR) grant - known as Linked Environments for Atmospheric Discovery (LEAD) - has been funded to facilitate the identification, access, preparation, assimilation, prediction, management, analysis, mining, and visualization of a broad array of meteorological data and model output, independent of format and physical location. A transforming element of LEAD is dynamic workflow orchestration and data management, which will allow use of analysis tools, forecast models, and data repositories as dynamically adaptive, on-demand systems that can a) change configuration rapidly and automatically in response to weather; b) continually be steered by new data; c) respond to decision-driven inputs from users; d) initiate other processes automatically; and e) steer remote observing technologies to optimize data collection for the problem at hand. Having been in operation for slightly more than a year, LEAD has created a technology roadmap and architecture for developing its capabilities and placing them within the academic and research environment. Further, much of the LEAD infrastructure being developed for the WRF model, particularly workflow orchestration, will play a significant role in the nascent WRF Developmental Test Bed Center located at NCAR. This paper updates the status of LEAD (e.g., the topics noted above), its ties with other community activities (e.g., CONDUIT, THREDDS, MADIS, NOMADS), and the manner in which LEAD technologies will be made available for general use. Each component LEAD application is being created as a standards-based Web service that can be run in stand-alone configuration or chained together to build an end-to-end environment for on-demand, real time NWP. We describe in this paper the concepts, implementation plans, and expected impacts of LEAD, the underpinning of which will be a series of interconnected, heterogeneous virtual IT "Grid environments" designed to provide a

  8. A Linked Data Approach for the Discovery of Educational ICT Tools in the Web of Data

    Ruiz-Calleja, Adolfo; Vega-Gorgojo, Guillermo; Asensio-Perez, Juan I.; Bote-Lorenzo, Miguel L.; Gomez-Sanchez, Eduardo; Alario-Hoyos, Carlos

    2012-01-01

    The use of Information and Communication Technologies (ICT) tools to support learning activities is nowadays generalized. Several educational registries provide information about ICT tools in order to help educators in their discovery and selection. These registries are typically isolated and require much effort to keep tool information up to…

  9. [Discoveries and techniques that have contributed to improving the treatment of pancreatic diseases].

    Navarro, Salvador

    2015-05-01

    Due to its retroperitoneal location, the pancreas has historically been a mysterious organ that is difficult to examine and which complicates treatment. The discovery of anesthesia and asepsis in the mid-19th century allowed laparotomic diagnosis, which was previously only possible at autopsy. The expectations of surgery were improved by the detection of blood groups, vitamin K synthesis, and the development of intensive care units. In addition, high levels of presurgical diagnosis and an unquestionable improvement of its results were enabled by advances in laboratory methods (serum quantification of amylase and lipase, tumoral markers, genetics, and techniques for measuring exocrine pancreatic function), imaging and endoscopic modalities, and fine tuning of surgical techniques. In this article, we review the history of the main milestones that have allowed progress in all these aspects. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  10. Knowledge Discovery in Biological Databases for Revealing Candidate Genes Linked to Complex Phenotypes.

    Hassani-Pak, Keywan; Rawlings, Christopher

    2017-06-13

    Genetics and "omics" studies designed to uncover genotype to phenotype relationships often identify large numbers of potential candidate genes, among which the causal genes are hidden. Scientists generally lack the time and technical expertise to review all relevant information available from the literature, from key model species and from a potentially wide range of related biological databases in a variety of data formats with variable quality and coverage. Computational tools are needed for the integration and evaluation of heterogeneous information in order to prioritise candidate genes and components of interaction networks that, if perturbed through potential interventions, have a positive impact on the biological outcome in the whole organism without producing negative side effects. Here we review several bioinformatics tools and databases that play an important role in biological knowledge discovery and candidate gene prioritization. We conclude with several key challenges that need to be addressed in order to facilitate biological knowledge discovery in the future.

  11. Microwave Photonics Techniques Supporting Flexible Wireless Communications Links

    Rommel, Simon; Cavalcante, Lucas Costa Pereira; Vegas Olmos, Juan José

    Wireless data communication links supporting the next generation 5G and beyond mobile networking face a set of engineering challenges related to the mandatory operation at mmw and higher frequency bands, provide capacities above 10 Gb/s, satisfy latency, robustness, flexibility and low complexity...

  12. Early phase drug discovery: cheminformatics and computational techniques in identifying lead series.

    Duffy, Bryan C; Zhu, Lei; Decornez, Hélène; Kitchen, Douglas B

    2012-09-15

    Early drug discovery processes rely on hit finding procedures followed by extensive experimental confirmation in order to select high priority hit series which then undergo further scrutiny in hit-to-lead studies. The experimental cost and the risk associated with poor selection of lead series can be greatly reduced by the use of many different computational and cheminformatic techniques to sort and prioritize compounds. We describe the steps in typical hit identification and hit-to-lead programs and then describe how cheminformatic analysis assists this process. In particular, scaffold analysis, clustering and property calculations assist in the design of high-throughput screening libraries, the early analysis of hits and then organizing compounds into series for their progression from hits to leads. Additionally, these computational tools can be used in virtual screening to design hit-finding libraries and as procedures to help with early SAR exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Literature-related discovery techniques applied to ocular disease : a vitreous restoration example

    Kostoff, Ronald N.; Los, Leonoor I.

    2013-01-01

    Purpose of reviewLiterature-related discovery and innovation (LRDI) is a text mining approach for bridging unconnected disciplines to hypothesize radical discovery. Application to medical problems involves identifying key disease symptoms, and identifying causes and treatments for those symptoms

  14. Brand Switching Pattern Discovery by Data Mining Techniques for the Telecommunication Industry in Australia

    Md Zahidul Islam

    2016-11-01

    Full Text Available There is more than one mobile-phone subscription per member of the Australian population. The number of complaints against the mobile-phone-service providers is also high. Therefore, the mobile service providers are facing a huge challenge in retaining their customers. There are a number of existing models to analyse customer behaviour and switching patterns. A number of switching models may also exist within a large market. These models are often not useful due to the heterogeneous nature of the market. Therefore, in this study we use data mining techniques to let the data talk to help us discover switching patterns without requiring us to use any models and domain knowledge. We use a variety of decision tree and decision forest techniques on a real mobile-phone-usage dataset in order to demonstrate the effectiveness of data mining techniques in knowledge discovery. We report many interesting patterns, and discuss them from a brand-switching and marketing perspective, through which they are found to be very sensible and interesting.

  15. Improving knowledge discovery from synthetic aperture radar images using the linked open data cloud and Sextant

    C. Nikolaou (Charalampos); K. Kyzirakos (Konstantinos); K. Bereta (Konstantina); K. Dogani (Kallirroi); S. Giannakopoulou (Stella); P. Smeros (Panayiotis); G. Garbis (George); M. Koubarakis (Manolis); D.E. Molina (Daniela); O.C. Dumitru (Octavian); G. Schwarz (Gottfried); M. Datcu (Mihai); P. Soille; M. Iapaolo; P.G. Marchetti; M. Datcu (Mihai); L. Colaiacomo

    2014-01-01

    htmlabstractIn the last few years, thanks to projects like TELEIOS, the linked open data cloud has been rapidly populated with geospatial data some of it describing Earth Observation products (e.g., CORINE Land Cover, Urban Atlas). The abundance of this data can prove very useful to the new missions

  16. Hybrid Multidimensional Relational and Link Analytical Knowledge Discovery for Law Enforcement

    Joslyn, Cliff A.; Gillen, David S.; Burke, John S.; Critchlow, Terence J.; Damante, Matt; Fernandes, Robert

    2008-08-01

    The challenges facing the Department of Homeland Security (DHS) require not only multi-dimensional, but also multi-scale data analysis. In particular, the ability to seamlessly move from summary information, such as trends, into detailed analysis of individual entities, while critical for law enforcement, typically requires manually transferring information among multiple tools. Such time-consuming and error prone processes significantly hamper the analysts' ability to quickly explore data and identify threats. As part of a DHS Science and Technology effort, we have been developing and deploying for Immigration and Customs Enforcement the CubeLink system integrating information between relational data cubes and link analytical semantic graphs. In this paper we describe CubeLink in terms of the underlying components, their integration, and the formal mapping from multidimensional data analysis into link analysis. In so doing, we provide a formal basis for one particular form of automatic schema-ontology mapping from OLAP data cubes to semantic graphs databases, and point the way towards future ``intelligent'' OLAP data cubes equipped with meta-data about their dimensional typing.

  17. Toxicophore exploration as a screening technology for drug design and discovery: techniques, scope and limitations.

    Singh, Pankaj Kumar; Negi, Arvind; Gupta, Pawan Kumar; Chauhan, Monika; Kumar, Raj

    2016-08-01

    Toxicity is a common drawback of newly designed chemotherapeutic agents. With the exception of pharmacophore-induced toxicity (lack of selectivity at higher concentrations of a drug), the toxicity due to chemotherapeutic agents is based on the toxicophore moiety present in the drug. To date, methodologies implemented to determine toxicophores may be broadly classified into biological, bioanalytical and computational approaches. The biological approach involves analysis of bioactivated metabolites, whereas the computational approach involves a QSAR-based method, mapping techniques, an inverse docking technique and a few toxicophore identification/estimation tools. Being one of the major steps in drug discovery process, toxicophore identification has proven to be an essential screening step in drug design and development. The paper is first of its kind, attempting to cover and compare different methodologies employed in predicting and determining toxicophores with an emphasis on their scope and limitations. Such information may prove vital in the appropriate selection of methodology and can be used as screening technology by researchers to discover the toxicophoric potentials of their designed and synthesized moieties. Additionally, it can be utilized in the manipulation of molecules containing toxicophores in such a manner that their toxicities might be eliminated or removed.

  18. Validation and discovery of genotype-phenotype associations in chronic diseases using linked data.

    Pathak, Jyotishman; Kiefer, Richard; Freimuth, Robert; Chute, Christopher

    2012-01-01

    This study investigates federated SPARQL queries over Linked Open Data (LOD) in the Semantic Web to validate existing, and potentially discover new genotype-phenotype associations from public datasets. In particular, we report our preliminary findings for identifying such associations for commonly occurring chronic diseases using the Online Mendelian Inheritance in Man (OMIM) and Database for SNPs (dbSNP) within the LOD knowledgebase and compare them with Gene Wiki for coverage and completeness. Our results indicate that Semantic Web technologies can play an important role for in-silico identification of novel disease-gene-SNP associations, although additional verification is required before such information can be applied and used effectively.

  19. KOJAK: Scalable Semantic Link Discovery Via Integrated Knowledge-Based and Statistical Reasoning

    2006-11-01

    group is pruned using a threshold to produce the final output. Table 1 Y2 Y2.5 Y3 Entities 10,000 10,000 100,000 Links 100,000 100,000 1,000,000 F...strongly connected they are to the seed members. Fourth, the ranked extended group is pruned using a threshold to produce the final output. The...people may eat at the same restaurant, drink coffee at the same cafe and take the same train to work every day without any strongly meaningful 34

  20. An experimental evaluation of the generalizing capabilities of process discovery techniques and black-box sequence models

    Tax, N.; van Zelst, S.J.; Teinemaa, I.; Gulden, Jens; Reinhartz-Berger, Iris; Schmidt, Rainer; Guerreiro, Sérgio; Guédria, Wided; Bera, Palash

    2018-01-01

    A plethora of automated process discovery techniques have been developed which aim to discover a process model based on event data originating from the execution of business processes. The aim of the discovered process models is to describe the control-flow of the underlying business process. At the

  1. Detection of spam web page using content and link-based techniques

    Spam pages are generally insufficient and inappropriate results for user. ... kinds of Web spamming techniques: Content spam and Link spam. 1. Content spam: The .... of the spam pages are machine generated and hence tech- nique of ...

  2. Harmonic elimination technique for a single-phase multilevel converter with unequal DC link voltage levels

    Ghasemi, N.; Zare, F.; Boora, A.A.

    2012-01-01

    Multilevel converters, because of the benefits they attract in generating high quality output voltage, are used in several applications. Various modulation and control techniques are introduced by several researchers to control the output voltage of the multilevel converters like space vector...... modulation and harmonic elimination (HE) methods. Multilevel converters may have a DC link with equal or unequal DC voltages. In this study a new HE technique based on the HE method is proposed for multilevel converters with unequal DC link voltage. The DC link voltage levels are considered as additional...

  3. Discovery of fuel cell anode electrocatalysts and dehydrogenation catalysts using combinatorial techniques

    Chan, Benny Chun Wai

    A gas diffusion optical screening method was developed for the discovery of catalysts for the electro-oxidation of reformate gas (H2 with 100 ppm CO). The screening cell was designed to accommodate a gas diffusion layer, 715 member catalyst array, and an electrolyte container. Since protons are generated during H2 oxidation, a pH sensitive fluorphore was used to identify active compositions. The cell showed no detectable iR drop across the array and ranked activity of two commercial PtRu and one Pt catalysts. Over 95% of a given catalyst fluoresced at the initial onset potential and a 5 mV difference in onset potential of two different catalysts was statistically different. A gas diffusion half cell was designed similar to the optical screening cell to obtain current-potential curves of bulk catalysts. The screening results correlated with half cell and fuel cell data, internally validating the method. The combinatorial method was then applied to search for catalysts in the PtRuMoIrRh composition space. The catalysts on the array were prepared by hydrogen reduction of the metals salts on carbon. The most active catalysts were from the Pt enriched regions of the PtRuMoRh quaternary. Bulk catalysts were prepared from the active regions and tested in the gas diffusion half cell. The most active catalysts in the optical screening were also the most active catalysts in the half cell. When any homemade catalysts were compared to commercial PtRu, however, the performance was worse. A high surface area, high catalyst activity synthetic method is the most important factor to reliably screen catalysts for "real world" fuel cell application. High surface area catalysts were tested for direct methanol oxidation activity. The optical screening method was compared with disk electrode, high throughput fuel cell testing, and fuel cell testing. Six catalysts examined included two commercial PtRu catalysts, a Pt catalyst, and three homemade PtRu catalysts of varying activity

  4. Data-Mining Techniques in Detecting Factors Linked to Academic Achievement

    Martínez Abad, Fernando; Chaparro Caso López, Alicia A.

    2017-01-01

    In light of the emergence of statistical analysis techniques based on data mining in education sciences, and the potential they offer to detect non-trivial information in large databases, this paper presents a procedure used to detect factors linked to academic achievement in large-scale assessments. The study is based on a non-experimental,…

  5. A Direct, Competitive Enzyme-Linked Immunosorbent Assay (ELISA) as a Quantitative Technique for Small Molecules

    Powers, Jennifer L.; Rippe, Karen Duda; Imarhia, Kelly; Swift, Aileen; Scholten, Melanie; Islam, Naina

    2012-01-01

    ELISA (enzyme-linked immunosorbent assay) is a widely used technique with applications in disease diagnosis, detection of contaminated foods, and screening for drugs of abuse or environmental contaminants. However, published protocols with a focus on quantitative detection of small molecules designed for teaching laboratories are limited. A…

  6. An Active Damping Technique for Small DC-Link Capacitor Based Drive System

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig; Lu, Kaiyuan

    2013-01-01

    A small dc-link capacitor based drive system shows instability when it is operated with large input line inductance at operating points with high power. This paper presents a simple, new active damping technique that can stabilize effectively the drive system at unstable operating points, offering...

  7. Application of data mining and artificial intelligence techniques to mass spectrometry data for knowledge discovery

    Hugo López-Fernández

    2016-05-01

    Full Text Available Mass spectrometry using matrix assisted laser desorption ionization coupled to time of flight analyzers (MALDI-TOF MS has become popular during the last decade due to its high speed, sensitivity and robustness for detecting proteins and peptides. This allows quickly analyzing large sets of samples are in one single batch and doing high-throughput proteomics. In this scenario, bioinformatics methods and computational tools play a key role in MALDI-TOF data analysis, as they are able handle the large amounts of raw data generated in order to extract new knowledge and useful conclusions. A typical MALDI-TOF MS data analysis workflow has three main stages: data acquisition, preprocessing and analysis. Although the most popular use of this technology is to identify proteins through their peptides, analyses that make use of artificial intelligence (AI, machine learning (ML, and statistical methods can be also carried out in order to perform biomarker discovery, automatic diagnosis, and knowledge discovery. In this research work, this workflow is deeply explored and new solutions based on the application of AI, ML, and statistical methods are proposed. In addition, an integrated software platform that supports the full MALDI-TOF MS data analysis workflow that facilitate the work of proteomics researchers without advanced bioinformatics skills has been developed and released to the scientific community.

  8. Emerging techniques for the discovery and validation of therapeutic targets for skeletal diseases.

    Cho, Christine H; Nuttall, Mark E

    2002-12-01

    Advances in genomics and proteomics have revolutionised the drug discovery process and target validation. Identification of novel therapeutic targets for chronic skeletal diseases is an extremely challenging process based on the difficulty of obtaining high-quality human diseased versus normal tissue samples. The quality of tissue and genomic information obtained from the sample is critical to identifying disease-related genes. Using a genomics-based approach, novel genes or genes with similar homology to existing genes can be identified from cDNA libraries generated from normal versus diseased tissue. High-quality cDNA libraries are prepared from uncontaminated homogeneous cell populations harvested from tissue sections of interest. Localised gene expression analysis and confirmation are obtained through in situ hybridisation or immunohistochemical studies. Cells overexpressing the recombinant protein are subsequently designed for primary cell-based high-throughput assays that are capable of screening large compound banks for potential hits. Afterwards, secondary functional assays are used to test promising compounds. The same overexpressing cells are used in the secondary assay to test protein activity and functionality as well as screen for small-molecule agonists or antagonists. Once a hit is generated, a structure-activity relationship of the compound is optimised for better oral bioavailability and pharmacokinetics allowing the compound to progress into development. Parallel efforts from proteomics, as well as genetics/transgenics, bioinformatics and combinatorial chemistry, and improvements in high-throughput automation technologies, allow the drug discovery process to meet the demands of the medicinal market. This review discusses and illustrates how different approaches are incorporated into the discovery and validation of novel targets and, consequently, the development of potentially therapeutic agents in the areas of osteoporosis and osteoarthritis

  9. Physical and data-link security techniques for future communication systems

    Tomasin, Stefano

    2016-01-01

     This book focuses on techniques that can be applied at the physical and data-link layers of communication systems in order to secure transmissions against eavesdroppers. Topics ranging from information theory-based security to coding for security and cryptography are discussed, with presentation of cutting-edge research and innovative results from leading researchers. The characteristic feature of all the contributions is their relevance for practical embodiments: detailed consideration is given to applications of security principles to a variety of widely used communication techniques such as multiantenna systems, ultra-wide band communication systems, power line communications, and quantum key distribution techniques. A further distinctive aspect is the attention paid to both unconditional and computational security techniques, providing a bridge between two usually distinct worlds. The book comprises extended versions of contributions delivered at the Workshop on Communication Security, held in Ancona, I...

  10. A Survey of Congestion Control Techniques and Data Link Protocols in Satellite Networks

    Fahmy, Sonia; Jain, Raj; Lu, Fang; Kalyanaraman, Shivkumar

    1998-01-01

    Satellite communication systems are the means of realizing a global broadband integrated services digital network. Due to the statistical nature of the integrated services traffic, the resulting rate fluctuations and burstiness render congestion control a complicated, yet indispensable function. The long propagation delay of the earth-satellite link further imposes severe demands and constraints on the congestion control schemes, as well as the media access control techniques and retransmissi...

  11. Data preparation techniques for a perinatal psychiatric study based on linked data.

    Xu, Fenglian; Hilder, Lisa; Austin, Marie-Paule; Sullivan, Elizabeth A

    2012-06-08

    In recent years there has been an increase in the use of population-based linked data. However, there is little literature that describes the method of linked data preparation. This paper describes the method for merging data, calculating the statistical variable (SV), recoding psychiatric diagnoses and summarizing hospital admissions for a perinatal psychiatric study. The data preparation techniques described in this paper are based on linked birth data from the New South Wales (NSW) Midwives Data Collection (MDC), the Register of Congenital Conditions (RCC), the Admitted Patient Data Collection (APDC) and the Pharmaceutical Drugs of Addiction System (PHDAS). The master dataset is the meaningfully linked data which include all or major study data collections. The master dataset can be used to improve the data quality, calculate the SV and can be tailored for different analyses. To identify hospital admissions in the periods before pregnancy, during pregnancy and after birth, a statistical variable of time interval (SVTI) needs to be calculated. The methods and SPSS syntax for building a master dataset, calculating the SVTI, recoding the principal diagnoses of mental illness and summarizing hospital admissions are described. Linked data preparation, including building the master dataset and calculating the SV, can improve data quality and enhance data function.

  12. Discovery of undefined protein cross-linking chemistry: a comprehensive methodology utilizing 18O-labeling and mass spectrometry.

    Liu, Min; Zhang, Zhongqi; Zang, Tianzhu; Spahr, Chris; Cheetham, Janet; Ren, Da; Zhou, Zhaohui Sunny

    2013-06-18

    Characterization of protein cross-linking, particularly without prior knowledge of the chemical nature and site of cross-linking, poses a significant challenge, because of their intrinsic structural complexity and the lack of a comprehensive analytical approach. Toward this end, we have developed a generally applicable workflow-XChem-Finder-that involves four stages: (1) detection of cross-linked peptides via (18)O-labeling at C-termini; (2) determination of the putative partial sequences of each cross-linked peptide pair using a fragment ion mass database search against known protein sequences coupled with a de novo sequence tag search; (3) extension to full sequences based on protease specificity, the unique combination of mass, and other constraints; and (4) deduction of cross-linking chemistry and site. The mass difference between the sum of two putative full-length peptides and the cross-linked peptide provides the formulas (elemental composition analysis) for the functional groups involved in each cross-linking. Combined with sequence restraint from MS/MS data, plausible cross-linking chemistry and site were inferred, and ultimately confirmed, by matching with all data. Applying our approach to a stressed IgG2 antibody, 10 cross-linked peptides were discovered and found to be connected via thioethers originating from disulfides at locations that had not been previously recognized. Furthermore, once the cross-link chemistry was revealed, a targeted cross-link search yielded 4 additional cross-linked peptides that all contain the C-terminus of the light chain.

  13. The application of a biometric identification technique for linking community and hospital data in rural Ghana.

    Odei-Lartey, Eliezer Ofori; Boateng, Dennis; Danso, Samuel; Kwarteng, Anthony; Abokyi, Livesy; Amenga-Etego, Seeba; Gyaase, Stephaney; Asante, Kwaku Poku; Owusu-Agyei, Seth

    2016-01-01

    The reliability of counts for estimating population dynamics and disease burdens in communities depends on the availability of a common unique identifier for matching general population data with health facility data. Biometric data has been explored as a feasible common identifier between the health data and sociocultural data of resident members in rural communities within the Kintampo Health and Demographic Surveillance System located in the central part of Ghana. Our goal was to assess the feasibility of using fingerprint identification to link community data and hospital data in a rural African setting. A combination of biometrics and other personal identification techniques were used to identify individual's resident within a surveillance population seeking care in two district hospitals. Visits from resident individuals were successfully recorded and categorized by the success of the techniques applied during identification. The successes of visits that involved identification by fingerprint were further examined by age. A total of 27,662 hospital visits were linked to resident individuals. Over 85% of those visits were successfully identified using at least one identification method. Over 65% were successfully identified and linked using their fingerprints. Supervisory support from the hospital administration was critical in integrating this identification system into its routine activities. No concerns were expressed by community members about the fingerprint registration and identification processes. Fingerprint identification should be combined with other methods to be feasible in identifying community members in African rural settings. This can be enhanced in communities with some basic Demographic Surveillance System or census information.

  14. The application of a biometric identification technique for linking community and hospital data in rural Ghana

    Odei-Lartey, Eliezer Ofori; Boateng, Dennis; Danso, Samuel; Kwarteng, Anthony; Abokyi, Livesy; Amenga-Etego, Seeba; Gyaase, Stephaney; Asante, Kwaku Poku; Owusu-Agyei, Seth

    2016-01-01

    Background The reliability of counts for estimating population dynamics and disease burdens in communities depends on the availability of a common unique identifier for matching general population data with health facility data. Biometric data has been explored as a feasible common identifier between the health data and sociocultural data of resident members in rural communities within the Kintampo Health and Demographic Surveillance System located in the central part of Ghana. Objective Our goal was to assess the feasibility of using fingerprint identification to link community data and hospital data in a rural African setting. Design A combination of biometrics and other personal identification techniques were used to identify individual's resident within a surveillance population seeking care in two district hospitals. Visits from resident individuals were successfully recorded and categorized by the success of the techniques applied during identification. The successes of visits that involved identification by fingerprint were further examined by age. Results A total of 27,662 hospital visits were linked to resident individuals. Over 85% of those visits were successfully identified using at least one identification method. Over 65% were successfully identified and linked using their fingerprints. Supervisory support from the hospital administration was critical in integrating this identification system into its routine activities. No concerns were expressed by community members about the fingerprint registration and identification processes. Conclusions Fingerprint identification should be combined with other methods to be feasible in identifying community members in African rural settings. This can be enhanced in communities with some basic Demographic Surveillance System or census information. PMID:26993473

  15. The application of a biometric identification technique for linking community and hospital data in rural Ghana

    Eliezer Ofori Odei-Lartey

    2016-03-01

    Full Text Available Background: The reliability of counts for estimating population dynamics and disease burdens in communities depends on the availability of a common unique identifier for matching general population data with health facility data. Biometric data has been explored as a feasible common identifier between the health data and sociocultural data of resident members in rural communities within the Kintampo Health and Demographic Surveillance System located in the central part of Ghana. Objective: Our goal was to assess the feasibility of using fingerprint identification to link community data and hospital data in a rural African setting. Design: A combination of biometrics and other personal identification techniques were used to identify individual's resident within a surveillance population seeking care in two district hospitals. Visits from resident individuals were successfully recorded and categorized by the success of the techniques applied during identification. The successes of visits that involved identification by fingerprint were further examined by age. Results: A total of 27,662 hospital visits were linked to resident individuals. Over 85% of those visits were successfully identified using at least one identification method. Over 65% were successfully identified and linked using their fingerprints. Supervisory support from the hospital administration was critical in integrating this identification system into its routine activities. No concerns were expressed by community members about the fingerprint registration and identification processes. Conclusions: Fingerprint identification should be combined with other methods to be feasible in identifying community members in African rural settings. This can be enhanced in communities with some basic Demographic Surveillance System or census information.

  16. Towards automating the discovery of certain innovative design principles through a clustering-based optimization technique

    Bandaru, Sunith; Deb, Kalyanmoy

    2011-09-01

    In this article, a methodology is proposed for automatically extracting innovative design principles which make a system or process (subject to conflicting objectives) optimal using its Pareto-optimal dataset. Such 'higher knowledge' would not only help designers to execute the system better, but also enable them to predict how changes in one variable would affect other variables if the system has to retain its optimal behaviour. This in turn would help solve other similar systems with different parameter settings easily without the need to perform a fresh optimization task. The proposed methodology uses a clustering-based optimization technique and is capable of discovering hidden functional relationships between the variables, objective and constraint functions and any other function that the designer wishes to include as a 'basis function'. A number of engineering design problems are considered for which the mathematical structure of these explicit relationships exists and has been revealed by a previous study. A comparison with the multivariate adaptive regression splines (MARS) approach reveals the practicality of the proposed approach due to its ability to find meaningful design principles. The success of this procedure for automated innovization is highly encouraging and indicates its suitability for further development in tackling more complex design scenarios.

  17. Networks systems and operations. [wideband communication techniques for data links with satellites

    1975-01-01

    The application of wideband communication techniques for data links with satellites is discussed. A diagram of the demand assigned voice communications system is provided. The development of prototype integrated spacecraft paramps at S- and C-bands is described and the performance of space-qualified paramps is tabulated. The characteristics of a dual parabolic cylinder monopulse zoom antenna for use with the tracking and data relay satellite system (TDRSS) are analyzed. The development of a universally applicable transponder at S-band is reported. A block diagram of the major subassemblies of the S-band transponder is included. The technology aspects of network timing and synchronization of communication systems are to show the use of the Omega navigation system. The telemetry data compression system used during the Skylab program is evaluated.

  18. Human factors assessment in PRA using Task Analysis Linked Evaluation Technique (TALENT)

    Wells, J.E.; Banks, W.W.

    1991-01-01

    Thirty years ago the US military and US aviation industry, and more recently, in response to the US Three Mile Island and USSR Chernobyl accidents, the US commercial nuclear power industry, acknowledged that human error, as an immediate precursor, and as a latent or indirect influence in the form of training, maintainability, inservice test, and surveillance programs, is a primary contributor to unreality and risk in complex high-reliability systems. A 1985 Nuclear Regulatory Commission (NRC) study of Licensee Event Reports (LERs) suggests that upwards of 65% of commercial nuclear system failures involve human error. Despite the magnitude and nature of human error cited in that study, there has been limited attention to personnel-centered issues, especially person-to-person issues involving group processes, management and organizational environment. The paper discusses NRC integration and applications research with respect to the Task Analysis Linked Evaluation Technique (TALENT) in risk assessment applications

  19. AFLP fragment isolation technique as a method to produce random sequences for single nucleotide polymorphism discovery in the green turtle, Chelonia mydas.

    Roden, Suzanne E; Dutton, Peter H; Morin, Phillip A

    2009-01-01

    The green sea turtle, Chelonia mydas, was used as a case study for single nucleotide polymorphism (SNP) discovery in a species that has little genetic sequence information available. As green turtles have a complex population structure, additional nuclear markers other than microsatellites could add to our understanding of their complex life history. Amplified fragment length polymorphism technique was used to generate sets of random fragments of genomic DNA, which were then electrophoretically separated with precast gels, stained with SYBR green, excised, and directly sequenced. It was possible to perform this method without the use of polyacrylamide gels, radioactive or fluorescent labeled primers, or hybridization methods, reducing the time, expense, and safety hazards of SNP discovery. Within 13 loci, 2547 base pairs were screened, resulting in the discovery of 35 SNPs. Using this method, it was possible to yield a sufficient number of loci to screen for SNP markers without the availability of prior sequence information.

  20. SU-E-T-191: PITSTOP: Process Improvement Techniques, Software Tools, and Operating Principles for a Quality Initiative Discovery Framework.

    Siochi, R

    2012-06-01

    To develop a quality initiative discovery framework using process improvement techniques, software tools and operating principles. Process deviations are entered into a radiotherapy incident reporting database. Supervisors use an in-house Event Analysis System (EASy) to discuss incidents with staff. Major incidents are analyzed with an in-house Fault Tree Analysis (FTA). A meta-Analysis is performed using association, text mining, key word clustering, and differential frequency analysis. A key operating principle encourages the creation of forcing functions via rapid application development. 504 events have been logged this past year. The results for the key word analysis indicate that the root cause for the top ranked key words was miscommunication. This was also the root cause found from association analysis, where 24% of the time that an event involved a physician it also involved a nurse. Differential frequency analysis revealed that sharp peaks at week 27 were followed by 3 major incidents, two of which were dose related. The peak was largely due to the front desk which caused distractions in other areas. The analysis led to many PI projects but there is still a major systematic issue with the use of forms. The solution we identified is to implement Smart Forms to perform error checking and interlocking. Our first initiative replaced our daily QA checklist with a form that uses custom validation routines, preventing therapists from proceeding with treatments until out of tolerance conditions are corrected. PITSTOP has increased the number of quality initiatives in our department, and we have discovered or confirmed common underlying causes of a variety of seemingly unrelated errors. It has motivated the replacement of all forms with smart forms. © 2012 American Association of Physicists in Medicine.

  1. Human factors assessment in PRA using task analysis linked evaluation technique (TALENT)

    Wells, J.E.; Banks, W.W.

    1990-01-01

    Human error is a primary contributor to risk in complex high-reliability systems. A 1985 U.S. Nuclear Regulatory Commission (USNRC) study of licensee event reports (LERs) suggests that upwards of 65% of commercial nuclear system failures involve human error. Since then, the USNRC has initiated research to fully and properly integrate human errors into the probabilistic risk assessment (PRA) process. The resulting implementation procedure is known as the Task Analysis Linked Evaluation Technique (TALENT). As indicated, TALENT is a broad-based method for integrating human factors expertise into the PRA process. This process achieves results which: (1) provide more realistic estimates of the impact of human performance on nuclear power safety, (2) can be fully audited, (3) provide a firm technical base for equipment-centered and personnel-centered retrofit/redesign of plants enabling them to meet internally and externally imposed safety standards, and (4) yield human and hardware data capable of supporting inquiries into human performance issues that transcend the individual plant. The TALENT procedure is being field-tested to verify its effectiveness and utility. The objectives of the field-test are to examine (1) the operability of the process, (2) its acceptability to the users, and (3) its usefulness for achieving measurable improvements in the credibility of the analysis. The field-test will provide the information needed to enhance the TALENT process

  2. Analysis of voltage modulation based active damping techniques for small DC-link drive system

    Wang, Dong; Lu, Kaiyuan; Rasmussen, Peter Omand

    2015-01-01

    Small DC-link drive system, built with film capacitor in the DC link, may have the advantages of longer lifetime and the possibility to achieve a more compact design of capacitor bank at medium and high power rates. However, it exhibits instability problem, especially when it is fed by a soft grid...

  3. ASM Inaugural Lecture 2010: Single crystal X-ray structural determination: A powerful technique for natural products research and drug discovery

    Fun Hoong Kun; Chantrapromma, S.; Boonnak, N.; Lee, V.S.

    2010-01-01

    Drug discovery from natural products resources have been extensively studied worldwide because natural products with their great structural diversity have traditionally provided most of the drugs in use. They offer major opportunities for finding novel low molecular weight leading-structures that are active against a wide range of assay targets. The most important step in the discovery process is the identification of compounds with interesting biological activity. Single crystal X-ray structure determination is a powerful technique for natural products research and drug discovery. The detailed three-dimensional structures that emerge can be co-related to the activities to these structures. In this article the following is presented: (i) co-crystal and disorder structures; (ii) determination of absolute configuration and (iii) the ability to distinguish between whether a natural product compound is a natural product or a natural product artifact. All these three properties are unique to the technique of single crystal X-ray structure determination. Case (iii) was demonstrated with a compound containing a chromene ring, namely macluraxanthone (which was isolated from Cratoxylum formosum subsp. pruniflorum, a Thai medicinal plant). (author)

  4. Nonlinear control techniques of a controllable rectifier/inverter-motor drive system with a small dc-link capacitor

    Liutanakul, Pisit; Pierfederici, Serge; Meibody-Tabar, Farid

    2008-01-01

    The necessity of the converters compactness in many applications imposes the reduction of their different components size when it is possible. In this paper, a control method allowing the use of a small size dc-link capacitor for the cascade of voltage controlled-rectifier/inverter-motor drive system is proposed. This is achieved by adding the power balance equation in the system's model and the application of an exact input/output feedback linearization technique in a way that the rectifier controller compensates any sudden change in the inverter load, which is here an induction motor. Since the exact input/output feedback linearization technique is sensitive to the uncertainties over system parameters, a robust control strategy based on sliding mode controller is proposed. By this approach, the dc-link voltage becomes almost insensitive to the load variations. As a result, the level of the dc-link voltage could be stabilized with a small size dc-link capacitor. Without any considerations of the RMS current stress on this dc-link capacitor, a calculation method of a minimum value of this capacitor based on its storage energy is proposed. All the investigations are shown by computer simulations and the performance of controlled system is verified by experimentation results

  5. Active damping technique for small DC-link capacitor based drive system

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig; Henriksen, Bjarne

    2010-01-01

    A detailed model of Adjustable Speed Drive (ASD) is discussed, which yield a general rule for active damping in a small DC link based drive. A desired value of input LC resonance damping coefficient can be achieved by changing gain parameters. The modified state space matrix due to active damping...

  6. Micro-enzyme-linked immunosorbent assay (ELISA) and radioimmunosorbent technique (RIST) for the detection of immunity to clinical tetanus

    Layton, G T [Royal Infirmary, Manchester (UK)

    1980-10-01

    Enzyme-linked immunosorbent assay (ELISA), and radioimmunosorbent assay (RIST) techniques for the detection of tetanus toxin antibodies are described. Both methods proved to be highly sensitive, and allowed the measurement of 5 x 10/sup -3/ units/ml tetanus antitoxin in human serum or plasma, sensitivity and reproducibility comparing well with other techniques previously described, and being superior to haemagglutination and latex agglutination tests. Results of the two methods correlated well, and reflected the immunization histories obtained. Micro ELISA and micro RIST would seem to be suitable for the detection of immunity, or non-immunity to clinical tetanus.

  7. A micro-enzyme-linked immunosorbent assay (ELISA) and radioimmunosorbent technique (RIST) for the detection of immunity to clinical tetanus

    Layton, G.T.

    1980-01-01

    Enzyme-linked immunosorbent assay (ELISA), and radioimmunosorbent assay (RIST) techniques for the detection of tetanus toxin antibodies are described. Both methods proved to be highly sensitive, and allowed the measurement of 5 x 10 -3 units/ml tetanus antitoxin in human serum or plasma, sensitivity and reproducibility comparing well with other techniques previously described, and being superior to haemagglutination and latex agglutination tests. Results of the two methods correlated well, and reflected the immunization histories obtained. Micro ELISA and micro RIST would seem to be suitable for the detection of immunity, or non-immunity to clinical tetanus. (author)

  8. Disease Compass- a navigation system for disease knowledge based on ontology and linked data techniques.

    Kozaki, Kouji; Yamagata, Yuki; Mizoguchi, Riichiro; Imai, Takeshi; Ohe, Kazuhiko

    2017-06-19

    Medical ontologies are expected to contribute to the effective use of medical information resources that store considerable amount of data. In this study, we focused on disease ontology because the complicated mechanisms of diseases are related to concepts across various medical domains. The authors developed a River Flow Model (RFM) of diseases, which captures diseases as the causal chains of abnormal states. It represents causes of diseases, disease progression, and downstream consequences of diseases, which is compliant with the intuition of medical experts. In this paper, we discuss a fact repository for causal chains of disease based on the disease ontology. It could be a valuable knowledge base for advanced medical information systems. We developed the fact repository for causal chains of diseases based on our disease ontology and abnormality ontology. This section summarizes these two ontologies. It is developed as linked data so that information scientists can access it using SPARQL queries through an Resource Description Framework (RDF) model for causal chain of diseases. We designed the RDF model as an implementation of the RFM for the fact repository based on the ontological definitions of the RFM. 1554 diseases and 7080 abnormal states in six major clinical areas, which are extracted from the disease ontology, are published as linked data (RDF) with SPARQL endpoint (accessible API). Furthermore, the authors developed Disease Compass, a navigation system for disease knowledge. Disease Compass can browse the causal chains of a disease and obtain related information, including abnormal states, through two web services that provide general information from linked data, such as DBpedia, and 3D anatomical images. Disease Compass can provide a complete picture of disease-associated processes in such a way that fits with a clinician's understanding of diseases. Therefore, it supports user exploration of disease knowledge with access to pertinent information

  9. Scleral wound healing with cross-link technique using riboflavin and ultraviolet A on rabbit eyes

    Damasceno NA

    2017-07-01

    Full Text Available Nadyr A Damasceno,1 Nadia C Miguel,2 Marcelo Palis Ventura,3 Miguel Burnier Jr,4 Marcos P Avila,5 Eduardo F Damasceno3 1Ophthalmology Department, Hospital Naval Marcílio Dias, 2Laboratory of Neurohistology and Cell Ultrastructure, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 3Ophthalmology Department, Universidade Federal Fluminense, Niterói, Brazil; 4Ophthalmology Department, McGill University, Montreal, QC, Canada; 5Ophthalmology Department, Universidade Federal de Goiás, Goiania, Brazil Purpose: The aim of study was to evaluate the cross-link using riboflavin and ultraviolet A (UVA for improving scleral wound healing.Materials and methods: This was an experimental study involving four New Zealand rabbits (eight eyes. Therapy procedure was chosen for the right eye and control procedure for the left one. UVA irradiation of 365 nm with a surface irradiance of 3 mW/cm2 and a photosensitizer of riboflavin drops were applied for 30 minutes on the right eye at 2 mm from the limbus. Sclerotomy incision was performed at 2 mm from the limbus in both right (on the cross-link-treated area and left eye. Then, 30 days after surgery, a morphological analysis and histological staining with hematoxylin–eosin and picrosirius red were performed, and the sclerotomy cicatrization of right and left eyes was compared. The variables investigated were as follows: sclerotomy incision pictures and measurements were made using the ImageJ Software. Scleral thickness was measured (employing the anterior optical coherence tomography and the digital caliper. Collagen fiber density stained with picrosirius red staining was measured using the Image Pro Plus software.Results: The morphological analysis showed that in all samples, the right eye presented sclerotomy closure, and in two eyes, among them, there were no visible edges of the sclerotomies incision. The left eye presented sclerotomy closure and incision edges

  10. Links between the discovery of primates and anatomical comparisons with humans, the chain of being, our place in nature, and racism.

    Diogo, Rui

    2018-04-01

    I focus on the crucial links between the discovery of nonhuman primates by Westerners, discussions on our place in nature, the chain of being, racism, and the history of primate comparative anatomy and of so-called "anatomical human racial studies." Strikingly, for more than a millennium humans knew more about the internal anatomy of a single monkey species than about that of their own bodies. This is because Galen used monkeys to infer human anatomy, in line with the human-animal continuity implied by the Greek notion of scala naturae. With the rise of Christianity, nonhuman primates were increasingly seen in a negative way. A more positive view emerged in the 14th century when nonhuman primates were directly studied/seen by Europeans, culminating in Tyson's 1699 work showing that chimps share more gross anatomical similarities with humans than with monkeys. However, the discomfort caused by this human-chimp similarity then led to a new idea of animal-human discontinuity, now related not to anatomy but to "civilization": between Europeans vs. non-Europeans + other primates. Moreover, Linnaeus' Systema Naturae and the emergence of "anatomical racial studies" influenced by Camper's craniology then led to even more extreme ideas, such as the notion that Europeans were both mentally and morphologically "ideal." Unfortunately the biased and often incorrect "results" of such studies, combined with ideas based on Darwin's "struggle for survival", became crucial in propaganda that lead to the rise of eugenics in the end of the 19th/first half of 20th centuries and that culminated in Nazism. Since the 1950s there has been an emphasis on the continuity/unity between all human groups and other primates, in great part influenced by what happened during World War 2. Reviews such as this one are, therefore, particularly necessary to illuminate and guard against attitudes against "the Other" and racist ideologies that are re-emerging in modern political discourse across the

  11. [The role of communication techniques in the dissemination of programs linked to bioethics in Brazil].

    De Paul De Barchifontaine, Christian

    2013-01-01

    As everywhere in the world, Bioethics is still a very recent domain in Brazil. The first initiatives date from the middle 1980s and its history goes hand in hand with that of institutions which encouraged it or, as in certain cases, are in fact born from the intellectual movement created by this designation concerning this new domain of philosophical and scientific knowledge. We still do not have statistics regarding the participation of the media in disseminating Bioethics in Brazil, but, as the leader of an institution that pioneered educational programmes and initiatives linked to Bioethics that reach our whole country, one may say that we can point out that the Internet, in addition to being a communication medium, that is to say, communication by means of electronic mails, is the main media as regards access to and broadcasting of literary (philosophical and scientific) production in Bioethics today.

  12. Multidimensional process discovery

    Ribeiro, J.T.S.

    2013-01-01

    Typically represented in event logs, business process data describe the execution of process events over time. Business process intelligence (BPI) techniques such as process mining can be applied to get strategic insight into business processes. Process discovery, conformance checking and

  13. The OceanLink Project

    Narock, T.; Arko, R. A.; Carbotte, S. M.; Chandler, C. L.; Cheatham, M.; Finin, T.; Hitzler, P.; Krisnadhi, A.; Raymond, L. M.; Shepherd, A.; Wiebe, P. H.

    2014-12-01

    A wide spectrum of maturing methods and tools, collectively characterized as the Semantic Web, is helping to vastly improve the dissemination of scientific research. Creating semantic integration requires input from both domain and cyberinfrastructure scientists. OceanLink, an NSF EarthCube Building Block, is demonstrating semantic technologies through the integration of geoscience data repositories, library holdings, conference abstracts, and funded research awards. Meeting project objectives involves applying semantic technologies to support data representation, discovery, sharing and integration. Our semantic cyberinfrastructure components include ontology design patterns, Linked Data collections, semantic provenance, and associated services to enhance data and knowledge discovery, interoperation, and integration. We discuss how these components are integrated, the continued automated and semi-automated creation of semantic metadata, and techniques we have developed to integrate ontologies, link resources, and preserve provenance and attribution.

  14. Linking optical and electrical small amplitude perturbation techniques for dynamic performance characterization of dye solar cells.

    Halme, Janne

    2011-07-21

    This paper unifies the analytical models used widely but thus far mostly separately for electrical and optical small amplitude perturbation measurements of nanostructured electrochemical dye solar cells (DSC): electrochemical impedance spectroscopy (EIS), intensity-modulated photocurrent spectroscopy (IMPS) and intensity-modulated photovoltage spectroscopy (IMVS). The models are linked by expressing the kinetic boundary condition used for solving the time-dependent continuity equation of electrons in IMPS and IMVS analysis in terms of the series and parallel impedance components found in the complete equivalent circuit impedance model of DSC. As a result, analytical expressions are derived for potentiostatic IMPS and galvanostatic IMVS transfer functions of complete DSCs that are applicable at any operating point along the solar cell current-voltage (IV) curve. In agreement with the theory, impedance spectrum calculated as a ratio of IMVS and IMPS transfer functions measured near the maximum power point matches exactly with the impedance spectrum measured directly with EIS. Consequently, both IMPS-IMVS and EIS yield equal estimates for the electron diffusion length. The role of the chemical capacitance of the nanostructured semiconductor photoelectrode in the interpretation of the so-called RC attenuation of the IMPS response is clarified, as well as the capacitive frequency dispersion in IMPS and IMVS. This journal is © the Owner Societies 2011

  15. A cross disciplinary study of link decay and the effectiveness of mitigation techniques.

    Hennessey, Jason; Ge, Steven

    2013-01-01

    The dynamic, decentralized world-wide-web has become an essential part of scientific research and communication. Researchers create thousands of web sites every year to share software, data and services. These valuable resources tend to disappear over time. The problem has been documented in many subject areas. Our goal is to conduct a cross-disciplinary investigation of the problem and test the effectiveness of existing remedies. We accessed 14,489 unique web pages found in the abstracts within Thomson Reuters' Web of Science citation index that were published between 1996 and 2010 and found that the median lifespan of these web pages was 9.3 years with 62% of them being archived. Survival analysis and logistic regression were used to find significant predictors of URL lifespan. The availability of a web page is most dependent on the time it is published and the top-level domain names. Similar statistical analysis revealed biases in current solutions: the Internet Archive favors web pages with fewer layers in the Universal Resource Locator (URL) while WebCite is significantly influenced by the source of publication. We also created a prototype for a process to submit web pages to the archives and increased coverage of our list of scientific webpages in the Internet Archive and WebCite by 22% and 255%, respectively. Our results show that link decay continues to be a problem across different disciplines and that current solutions for static web pages are helping and can be improved.

  16. Non-invasive dendrochronology of late-medieval objects in Oslo: refinement of a technique and discoveries

    Daly, Aoife; Streeton, Noëlle L. W.

    2017-06-01

    A technique for non-invasive dendrochronological analysis of oak was developed for archaeological material, using an industrial CT scanner. Since 2013, this experience has been extended within the scope of the research project `After the Black Death: Painting and Polychrome Sculpture in Norway'. The source material for the project is a collection of late-medieval winged altarpieces, shrines, polychrome sculpture, and fragments from Norwegian churches, which are owned by the Museum of Cultural History, University of Oslo. The majority cannot be sampled, and many are too large to fit into the CT scanner. For these reasons, a combined approach was adopted, utilizing CT scanning where possible, but preceded by an `exposed-wood' imaging technique. Both non-invasive techniques have yielded reliable results, and CT scanning has confirmed the reliability of the imaging technique alone. This paper presents the analytical methods, along with results from two of the 13 objects under investigation. Results for reliable dates and provenances provide new foundations for historical interpretations.

  17. Undercovering the hidden links. Nuclear and isotope techniques target nutritional needs

    Iyengar, Venkatesh

    2001-01-01

    Global nutrition problems raise a host of questions and warrant action by the international community of scientists, nutritionists, physicians and other medical professionals. What steps should be taken to remedy this situation? How can this be accomplished economically? How can progress be monitored? What is the role of technology in the overall monitoring process? The last question, which is most relevant to this article, is of particular importance to the IAEA and its support of nutrition programmes. The IAEA's activities in human nutrition were initiated to apply nuclear and related isotopic techniques for solving problems prevalent in developing countries. Among the numerous applications available, isotopic techniques are uniquely well suited to targeting and tracking progress in food and nutrition development programmes. These are tools that help evaluate nutritional status of individuals and populations, measure nutrient requirements and the uptake and bio-availability of vitamins and minerals. The IAEA's efforts help to: verify the nature of the nutrition problem and the efficacy of specific interventions; implement nutrition intervention programmes by monitoring effectiveness and reducing programme costs; guide in the processing of local foods for optimal nutritional value; serve as early indicators of important long-term health improvements; and strengthen capacity building in developing countries. Among the numerous applications available, isotopic techniques are uniquely well suited to targeting and tracking progress in food and nutrition development programmes. These are tools that help evaluate nutritional status of individuals and populations, measure nutrient requirements and the uptake and bio-availability of vitamins and minerals. The IAEA's efforts help to: verify the nature of the nutrition problem and the efficacy of specific interventions; implement nutrition intervention programmes by monitoring effectiveness and reducing programme costs

  18. Data transmission techniques for short-range optical fiber and wireless communication links

    Pham, Tien Thang

    The research work described in this thesis is devoted to experimental investigation of techniques for cost-effective high-speed optical communications supporting both wired and wireless services. The main contributions of this thesis have expanded the state-of-the-art in two main areas: high......-speed optical/wireless integration and advanced modulation formats for intensity modulation with direct detection (IM/DD) optical systems. Regarding optical/wireless integration, this thesis focuses on integration of broadband ultra-wide band (UWB) and 60-GHz band wireless systems into optical fiber access...... networks to distribute wireless services in personal area networks (PANs). Photonic technologies to generate and distribute gigabit UWB and 60-GHz-band signals are proposed and demonstrated. Two novel methods are proposed and demonstrated to optically generate Federal Communications Commission (FCC...

  19. Bonding, Bridging, and Linking Social Capital and Self-Rated Health among Chinese Adults: Use of the Anchoring Vignettes Technique.

    He Chen

    Full Text Available Three main opposing camps exist over how social capital relates to population health, namely the social support perspective, the inequality thesis, and the political economy approach. The distinction among bonding, bridging, and linking social capital probably helps close the debates between these three camps, which is rarely investigated in existing literatures. Moreover, although self-rated health is a frequently used health indicator in studies on the relationship between social capital and health, the interpersonal incomparability of this measure has been largely neglected. This study has two main objectives. Firstly, we aim to investigate the relationship between bonding, bridging, and linking social capital and self-rated health among Chinese adults. Secondly, we aim to improve the interpersonal comparability in self-rated health measurement. We use data from a nationally representative survey in China. Self-rated health was adjusted using the anchoring vignettes technique to improve comparability. Two-level ordinal logistic regression was performed to model the association between social capital and self-rated health at both individual and community levels. The interaction between residence and social capital was included to examine urban/rural disparities in the relationship. We found that most social capital indicators had a significant relationship with adjusted self-rated health of Chinese adults, but the relationships were mixed. Individual-level bonding, linking social capital, and community-level bridging social capital were positively related with health. Significant urban/rural disparities appeared in the association between community-level bonding, linking social capital, and adjusted self-rated health. For example, people living in communities with higher bonding social capital tended to report poorer adjusted self-rated health in urban areas, but the opposite tendency held for rural areas. Furthermore, the comparison between

  20. Bonding, Bridging, and Linking Social Capital and Self-Rated Health among Chinese Adults: Use of the Anchoring Vignettes Technique.

    Chen, He; Meng, Tianguang

    2015-01-01

    Three main opposing camps exist over how social capital relates to population health, namely the social support perspective, the inequality thesis, and the political economy approach. The distinction among bonding, bridging, and linking social capital probably helps close the debates between these three camps, which is rarely investigated in existing literatures. Moreover, although self-rated health is a frequently used health indicator in studies on the relationship between social capital and health, the interpersonal incomparability of this measure has been largely neglected. This study has two main objectives. Firstly, we aim to investigate the relationship between bonding, bridging, and linking social capital and self-rated health among Chinese adults. Secondly, we aim to improve the interpersonal comparability in self-rated health measurement. We use data from a nationally representative survey in China. Self-rated health was adjusted using the anchoring vignettes technique to improve comparability. Two-level ordinal logistic regression was performed to model the association between social capital and self-rated health at both individual and community levels. The interaction between residence and social capital was included to examine urban/rural disparities in the relationship. We found that most social capital indicators had a significant relationship with adjusted self-rated health of Chinese adults, but the relationships were mixed. Individual-level bonding, linking social capital, and community-level bridging social capital were positively related with health. Significant urban/rural disparities appeared in the association between community-level bonding, linking social capital, and adjusted self-rated health. For example, people living in communities with higher bonding social capital tended to report poorer adjusted self-rated health in urban areas, but the opposite tendency held for rural areas. Furthermore, the comparison between multivariate analyses

  1. Simultaneously precise frequency transfer and time synchronization using feed-forward compensation technique via 120 km fiber link.

    Chen, Xing; Lu, Jinlong; Cui, Yifan; Zhang, Jian; Lu, Xing; Tian, Xusheng; Ci, Cheng; Liu, Bo; Wu, Hong; Tang, Tingsong; Shi, Kebin; Zhang, Zhigang

    2015-12-22

    Precision time synchronization between two remote sites is desired in many applications such as global positioning satellite systems, long-baseline interferometry, coherent radar detection and fundamental physics constant measurements. The recently developed frequency dissemination technologies based on optical fiber link have improved the transfer instability to the level of 10(-19)/day at remote location. Therefore it is possible to keep clock oscillation at remote locations continuously corrected, or to reproduce a "virtual" clock on the remote location. However the initial alignment and the correction of 1 pps timing signal from time to time are still required, besides the highly stabilized clock frequency transfer between distant locations. Here we demonstrate a time synchronization based on an ultra-stable frequency transfer system via 120-km commercial fiber link by transferring an optical frequency comb. Both the phase noise compensation in frequency dissemination and temporal basis alignment in time synchronization were implemented by a feed-forward digital compensation (FFDC) technique. The fractional frequency instability was measured to be 6.18 × 10(-20) at 2000 s. The timing deviation of time synchronization was measured to be 0.6 ps in 1500 s. This technique also can be applied in multi-node fiber network topology.

  2. A THEORETICAL FRAMEWORK FOR COMBINING TECHNIQUES THAT PROBE THE LINK BETWEEN GALAXIES AND DARK MATTER

    Leauthaud, Alexie; Tinker, Jeremy; Behroozi, Peter S.; Busha, Michael T.; Wechsler, Risa H.

    2011-01-01

    We develop a theoretical framework that combines measurements of galaxy-galaxy lensing, galaxy clustering, and the galaxy stellar mass function in a self-consistent manner. While considerable effort has been invested in exploring each of these probes individually, attempts to combine them are still in their infancy. These combinations have the potential to elucidate the galaxy-dark matter connection and the galaxy formation physics responsible for it, as well as to constrain cosmological parameters and to test the nature of gravity. In this paper, we focus on a theoretical model that describes the galaxy-dark matter connection based on standard halo occupation distribution techniques. Several key modifications enable us to extract additional parameters that determine the stellar-to-halo mass relation and to simultaneously fit data from multiple probes while allowing for independent binning schemes for each probe. We construct mock catalogs from numerical simulations to investigate the effects of sample variance and covariance for each probe. Finally, we analyze how trends in each of the three observables impact the derived parameters of the model. In particular, we investigate various features of the observed galaxy stellar mass function (low-mass slope, 'plateau', knee, and high-mass cutoff) and show how each feature is related to the underlying relationship between stellar and halo mass. We demonstrate that the observed 'plateau' feature in the stellar mass function at M * ∼ 2 x 10 10 M sun is due to the transition that occurs in the stellar-to-halo mass relation at M h ∼ 10 12 M sun from a low-mass power-law regime to a sub-exponential function at higher stellar mass.

  3. Linking Spatial Variations in Water Quality with Water and Land Management using Multivariate Techniques.

    Wan, Yongshan; Qian, Yun; Migliaccio, Kati White; Li, Yuncong; Conrad, Cecilia

    2014-03-01

    Most studies using multivariate techniques for pollution source evaluation are conducted in free-flowing rivers with distinct point and nonpoint sources. This study expanded on previous research to a managed "canal" system discharging into the Indian River Lagoon, Florida, where water and land management is the single most important anthropogenic factor influencing water quality. Hydrometric and land use data of four drainage basins were uniquely integrated into the analysis of 25 yr of monthly water quality data collected at seven stations to determine the impact of water and land management on the spatial variability of water quality. Cluster analysis (CA) classified seven monitoring stations into four groups (CA groups). All water quality parameters identified by discriminant analysis showed distinct spatial patterns among the four CA groups. Two-step principal component analysis/factor analysis (PCA/FA) was conducted with (i) water quality data alone and (ii) water quality data in conjunction with rainfall, flow, and land use data. The results indicated that PCA/FA of water quality data alone was unable to identify factors associated with management activities. The addition of hydrometric and land use data into PCA/FA revealed close associations of nutrients and color with land management and storm-water retention in pasture and citrus lands; total suspended solids, turbidity, and NO + NO with flow and Lake Okeechobee releases; specific conductivity with supplemental irrigation supply; and dissolved O with wetland preservation. The practical implication emphasizes the importance of basin-specific land and water management for ongoing pollutant loading reduction and ecosystem restoration programs. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  4. Volatility Discovery

    Dias, Gustavo Fruet; Scherrer, Cristina; Papailias, Fotis

    The price discovery literature investigates how homogenous securities traded on different markets incorporate information into prices. We take this literature one step further and investigate how these markets contribute to stochastic volatility (volatility discovery). We formally show...... that the realized measures from homogenous securities share a fractional stochastic trend, which is a combination of the price and volatility discovery measures. Furthermore, we show that volatility discovery is associated with the way that market participants process information arrival (market sensitivity......). Finally, we compute volatility discovery for 30 actively traded stocks in the U.S. and report that Nyse and Arca dominate Nasdaq....

  5. From Theory-Inspired to Theory-Based Interventions: A Protocol for Developing and Testing a Methodology for Linking Behaviour Change Techniques to Theoretical Mechanisms of Action.

    Michie, Susan; Carey, Rachel N; Johnston, Marie; Rothman, Alexander J; de Bruin, Marijn; Kelly, Michael P; Connell, Lauren E

    2018-05-18

    Understanding links between behaviour change techniques (BCTs) and mechanisms of action (the processes through which they affect behaviour) helps inform the systematic development of behaviour change interventions. This research aims to develop and test a methodology for linking BCTs to their mechanisms of action. Study 1 (published explicit links): Hypothesised links between 93 BCTs (from the 93-item BCT taxonomy, BCTTv1) and mechanisms of action will be identified from published interventions and their frequency, explicitness and precision documented. Study 2 (expert-agreed explicit links): Behaviour change experts will identify links between 61 BCTs and 26 mechanisms of action in a formal consensus study. Study 3 (integrated matrix of explicit links): Agreement between studies 1 and 2 will be evaluated and a new group of experts will discuss discrepancies. An integrated matrix of BCT-mechanism of action links, annotated to indicate strength of evidence, will be generated. Study 4 (published implicit links): To determine whether groups of co-occurring BCTs can be linked to theories, we will identify groups of BCTs that are used together from the study 1 literature. A consensus exercise will be used to rate strength of links between groups of BCT and theories. A formal methodology for linking BCTs to their hypothesised mechanisms of action can contribute to the development and evaluation of behaviour change interventions. This research is a step towards developing a behaviour change 'ontology', specifying relations between BCTs, mechanisms of action, modes of delivery, populations, settings and types of behaviour.

  6. Toward rapid analysis, forecast and discovery of bioactive compounds from herbs by jointly using thin layer chromatography and ratiometric surface-enhanced Raman spectroscopy technique.

    Gu, Xiaoling; Jin, Yang; Dong, Fang; Cai, Yueqing; You, Zhengyi; You, Junhui; Zhang, Liying; Du, Shuhu

    2018-05-10

    Conventional isolation and identification of active compounds from herbs have been extensively reported by using various chromatographic and spectroscopic techniques. However, how to quickly discover new bioactive ingredients from natural sources still remains a challenging task due to the interference of their similar structures or matrices. Here, we present a grand approach for rapid analysis, forecast and discovery of bioactive compounds from herbs based on a hyphenated strategy of thin layer chromatography and ratiometric surface-enhanced Raman spectroscopy. The performance of the hyphenated strategy is first evaluated by analyzing four protoberberine alkaloids, berberine (BER), coptisine (COP), palmatine (PAT) and jatrorrhizine (JAT), from a typical herb Coptidis Rhizoma as an example. It has been demonstrated that this coupling method can identify the four compounds by characteristic peaks at 728, 708, 736 and 732 cm -1 , and especially discriminate BER and COP (with similar migration distances) by ratiometric Raman intensity (I 708 /I 728 ). The corresponding limits of detection are 0.1, 0.05, 0.1 and 0.5 μM, respectively, which are about 1-2 orders of magnitude lower than those of direct observation method under 254 nm UV lamp. Based on these findings, the proposed method further guides forecast and discovery of unknown compounds from traditional Chinese herb Typhonii Rhizoma. Results infer that two trace alkaloids (BER and COP) from the n-butanol extract of Typhonii Rhizoma are found for the first time. Moreover, in vitro experiments manifest that BER can effectively decrease the viability of human glioma U87 cells by inducing cell cycle arrest in a concentration-dependent manner. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Evaluating the potential of natural reproduction and artificial techniques to increase Acropora cervicornis populations at Discovery Bay, Jamaica

    Norman J Quinn

    2006-12-01

    Full Text Available Shallow water Acropora species have become uncommon on north coast Jamaican coral reefs owing to a number of factors. On many reefs, algae have taken their place. The result is loss of habitat for many species of fish and invertebrates and less attractive reefs with fewer fish. These reefs appear to be prime candidates for coral restoration. However, the potential for coral to naturally recover should be examined before efforts to restore reefs are undertaken. Reef restoration is unnecessary if the population has the capacity to recovery through natural means. We observed that the rate of settlement of Acropora spat in the Caribbean is much lower than the spat settlement rate of several other Caribbean coral families and much lower than Acropora spat settlement rates in the South Pacific. A very low percentage of apparently healthy colonies of A. cervicornis possessed developing gametes in July 2005, a month before spawning. It appears that the long-term survival of remnant A. cervicornis populations is threatened unless successful sexual reproduction is restored. Several techniques were used to test transplant methods for restoring A. cervicornis populations. The mean survivorship and growth rate of one technique was >75% and nearly 250% per annum, respectively. Working with hotel operators, environmental groups, and local fishers, we are attempting to reintroduce A. cervicornis to sites where it previously existed and increase coral biomass and complexity at these sites. Reefs with greater A. cervicornis biomass have larger edible fish populations. With localized protection of these restored reefs we anticipate an increase of larger edible fish not only on reefs within the restored protected areas but also on adjacent reefs. Furthermore, increased coral and fish biodiversity improves the attractiveness of the reef community for divers and snorkelers. Rev. Biol. Trop. 54 (Suppl. 3: 105-116. Epub 2007 Jan. 15.Las especies someras de Acropora se

  8. Introduction to fragment-based drug discovery.

    Erlanson, Daniel A

    2012-01-01

    Fragment-based drug discovery (FBDD) has emerged in the past decade as a powerful tool for discovering drug leads. The approach first identifies starting points: very small molecules (fragments) that are about half the size of typical drugs. These fragments are then expanded or linked together to generate drug leads. Although the origins of the technique date back some 30 years, it was only in the mid-1990s that experimental techniques became sufficiently sensitive and rapid for the concept to be become practical. Since that time, the field has exploded: FBDD has played a role in discovery of at least 18 drugs that have entered the clinic, and practitioners of FBDD can be found throughout the world in both academia and industry. Literally dozens of reviews have been published on various aspects of FBDD or on the field as a whole, as have three books (Jahnke and Erlanson, Fragment-based approaches in drug discovery, 2006; Zartler and Shapiro, Fragment-based drug discovery: a practical approach, 2008; Kuo, Fragment based drug design: tools, practical approaches, and examples, 2011). However, this chapter will assume that the reader is approaching the field with little prior knowledge. It will introduce some of the key concepts, set the stage for the chapters to follow, and demonstrate how X-ray crystallography plays a central role in fragment identification and advancement.

  9. Beyond Discovery

    Korsgaard, Steffen; Sassmannshausen, Sean Patrick

    2017-01-01

    In this chapter we explore four alternatives to the dominant discovery view of entrepreneurship; the development view, the construction view, the evolutionary view, and the Neo-Austrian view. We outline the main critique points of the discovery presented in these four alternatives, as well...

  10. Chemical Discovery

    Brown, Herbert C.

    1974-01-01

    The role of discovery in the advance of the science of chemistry and the factors that are currently operating to handicap that function are considered. Examples are drawn from the author's work with boranes. The thesis that exploratory research and discovery should be encouraged is stressed. (DT)

  11. DISCOVERY OF SiCSi IN IRC+10216: A MISSING LINK BETWEEN GAS AND DUST CARRIERS OF Si–C BONDS

    Cernicharo, J.; Agúndez, M.; Prieto, L. Velilla; Quintana-Lacaci, G. [Group of Molecular Astrophysics, ICMM, CSIC, C/Sor Juana Inés de La Cruz N3, E-28049, Madrid (Spain); McCarthy, M. C.; Gottlieb, C. A.; Drumel, M. A. Martin-; Patel, N. A.; Reilly, N. J.; Young, K. H. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138, and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138 (United States); Baraban, J. H. [Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 (United States); Changala, P. B. [JILA, National Institute of Standards and Technology and University of Colorado, and Department of Physics, University of Colorado, Boulder, CO 80309 (United States); Guélin, M. [Institut de Radioastronomie Millimétrique, 300 rue de la Piscine, F-38406 St-Martin d’Hères (France); Kahane, C. [Universit Grenoble Alpes, IPAG, F-38000 Grenoble (France); CNRS, IPAG, F-38000 Grenoble (France); Stanton, J. F. [Institute for Theoretical Chemistry, Department of Chemistry, The University of Texas at Austin, Austin, TX 78712 (United States); Thorwirth, S. [I. Physikalisches Institut, Universität zu Köln, Zülpicher Str. 77, D-50937 Köln (Germany)

    2015-06-10

    We report the discovery in space of a disilicon species, SiCSi, from observations between 80 and 350 GHz with the IRAM 30 m radio telescope. Owing to the close coordination between laboratory experiments and astrophysics, 112 lines have now been detected in the carbon-rich star CW Leo. The derived frequencies yield improved rotational and centrifugal distortion constants up to sixth order. From the line profiles and interferometric maps with the Submillimeter Array, the bulk of the SiCSi emission arises from a region of 6″ in radius. The derived abundance is comparable to that of SiC{sub 2}. As expected from chemical equilibrium calculations, SiCSi and SiC{sub 2} are the most abundant species harboring a Si−C bond in the dust formation zone and certainly both play a key role in the formation of SiC dust grains.

  12. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action.

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

  13. Transport theory calculation for a heterogeneous multi-assembly problem by characteristics method with direct neutron path linking technique

    Kosaka, Shinya; Saji, Etsuro

    2000-01-01

    A characteristics transport theory code, CHAPLET, has been developed for the purpose of making it practical to perform a whole LWR core calculation with the same level of calculational model and accuracy as that of an ordinary single assembly calculation. The characteristics routine employs the CACTUS algorithm for drawing ray tracing lines, which assists the two key features of the flux solution in the CHAPLET code. One is the direct neutron path linking (DNPL) technique which strictly connects angular fluxes at each assembly interface in the flux solution separated between assemblies. Another is to reduce the required memory storage by sharing the data related to ray tracing among assemblies with the same configuration. For faster computation, the coarse mesh rebalance (CMR) method and the Aitken method were incorporated in the code and the combined use of both methods showed the most promising acceleration performance among the trials. In addition, the parallelization of the flux solution was attempted, resulting in a significant reduction in the wall-clock time of the calculation. By all these efforts, coupled with the results of many verification studies, a whole LWR core heterogeneous transport theory calculation finally became practical. CHAPLET is thought to be a useful tool which can produce the reference solutions for analyses of an LWR (author)

  14. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens. PMID:27625608

  15. Representation Discovery using Harmonic Analysis

    Mahadevan, Sridhar

    2008-01-01

    Representations are at the heart of artificial intelligence (AI). This book is devoted to the problem of representation discovery: how can an intelligent system construct representations from its experience? Representation discovery re-parameterizes the state space - prior to the application of information retrieval, machine learning, or optimization techniques - facilitating later inference processes by constructing new task-specific bases adapted to the state space geometry. This book presents a general approach to representation discovery using the framework of harmonic analysis, in particu

  16. Higgs Discovery

    Sannino, Francesco

    2013-01-01

    has been challenged by the discovery of a not-so-heavy Higgs-like state. I will therefore review the recent discovery \\cite{Foadi:2012bb} that the standard model top-induced radiative corrections naturally reduce the intrinsic non-perturbative mass of the composite Higgs state towards the desired...... via first principle lattice simulations with encouraging results. The new findings show that the recent naive claims made about new strong dynamics at the electroweak scale being disfavoured by the discovery of a not-so-heavy composite Higgs are unwarranted. I will then introduce the more speculative......I discuss the impact of the discovery of a Higgs-like state on composite dynamics starting by critically examining the reasons in favour of either an elementary or composite nature of this state. Accepting the standard model interpretation I re-address the standard model vacuum stability within...

  17. A simplification of the enzyme-linked immunospot technique. Increased sensitivity for cells secreting IgG antibodies to Haemophilus influenzae type b capsular polysaccharide

    Barington, T; Sparholt, S; Juul, L

    1992-01-01

    A simplified enzyme-linked immunospot (ELISPOT) technique is described for the detection of cells secreting antibodies to tetanus toxoid (TT), diphtheria toxoid (DT) or Haemophilus influenzae type b capsular polysaccharide (PRP). By combining the cell suspension with the enzyme-linked secondary...... antibodies in one incubation, the second incubation and washing procedure could be omitted from the original technique. The simplified assay had the same sensitivity for anti-TT and anti-DT spot-forming cells as the ordinary ELISPOT assay. The IgG anti-PRP spots were, however, improved both in quality...... and in quantity (median: 40% more spots), while the detection of IgM and IgA anti-PRP spot-forming cells was the same in the two techniques. This simplified technique can probably also be used to save time in other antigen systems and should be considered when designing ELISPOT assays for the detection...

  18. Development of a Focused Library of Triazole-Linked Privileged-Structure-Based Conjugates Leading to the Discovery of Novel Phenotypic Hits against Protozoan Parasitic Infections.

    Uliassi, Elisa; Piazzi, Lorna; Belluti, Federica; Mazzanti, Andrea; Kaiser, Marcel; Brun, Reto; Moraes, Carolina B; Freitas-Junior, Lucio H; Gul, Sheraz; Kuzikov, Maria; Ellinger, Bernhard; Borsari, Chiara; Costi, Maria Paola; Bolognesi, Maria Laura

    2018-04-06

    Protozoan infections caused by Plasmodium, Leishmania, and Trypanosoma spp. contribute significantly to the burden of infectious diseases worldwide, causing severe morbidity and mortality. The inadequacy of available treatments calls for cost- and time-effective drug discovery endeavors. To this end, we envisaged the triazole linkage of privileged structures as an effective drug design strategy to generate a focused library of high-quality compounds. The versatility of this approach was combined with the feasibility of a phenotypic assay, integrated with early ADME-tox profiling. Thus, an 18-membered library was efficiently assembled via Huisgen cycloaddition of phenothiazine, biphenyl, and phenylpiperazine scaffolds. The resulting 18 compounds were then tested against seven parasite strains, and counter-screened for selectivity against two mammalian cell lines. In parallel, hERG and cytochrome P450 (CYP) inhibition, and mitochondrial toxicity were assessed. Remarkably, 10-((1-(3-([1,1'-biphenyl]-3-yloxy)propyl)-1H-1,2,3-triazol-5-yl)methyl)-10H-phenothiazine (7) and 10-(3-(1-(3-([1,1'-biphenyl]-3-yloxy)propyl)-1H-1,2,3-triazol-4-yl)propyl)-10H-phenothiazine (12) showed respective IC 50 values of 1.8 and 1.9 μg mL -1 against T. cruzi, together with optimal selectivity. In particular, compound 7 showed a promising ADME-tox profile. Thus, hit 7 might be progressed as an antichagasic lead. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Discovery Mondays

    2003-01-01

    Many people don't realise quite how much is going on at CERN. Would you like to gain first-hand knowledge of CERN's scientific and technological activities and their many applications? Try out some experiments for yourself, or pick the brains of the people in charge? If so, then the «Lundis Découverte» or Discovery Mondays, will be right up your street. Starting on May 5th, on every first Monday of the month you will be introduced to a different facet of the Laboratory. CERN staff, non-scientists, and members of the general public, everyone is welcome. So tell your friends and neighbours and make sure you don't miss this opportunity to satisfy your curiosity and enjoy yourself at the same time. You won't have to listen to a lecture, as the idea is to have open exchange with the expert in question and for each subject to be illustrated with experiments and demonstrations. There's no need to book, as Microcosm, CERN's interactive museum, will be open non-stop from 7.30 p.m. to 9 p.m. On the first Discovery M...

  20. Trypanosomosis surveillance on Zanzibar island, using the trypanosomal antigen detection ELISA (enzyme-linked immunosorbent assay) technique

    Mbwambo, H A [Animal Disease Research Inst. (ADRI), Dar-es-Salaam (Tanzania, United Republic of)

    1997-02-01

    The effectiveness of trypanosomosis control programs depends greatly on prior knowledge of basic data of the epidemiological situation of the disease, which in turns depends, among others, on the use of techniques that give a fairly quick and accurate diagnosis. An antigen-detection (Ag) ELISA was first introduced into Tanzania and validated at the Animal Disease Research Institute (ADRI) through the FAO/IAEA Research Contract (RC) No. 5030/NL. Incorporation of the Ag-ELISA technique into a FAO animal disease control project (1986-1993) on Unguja island, in 1992, revealed useful information of high trypanosomosis prevalence in an area previously declared free of the disease using just stained blood smears and buffy coat examinations. This triggered further efforts into more intensive surveys of the tsetse and trypanosomosis situation on Unguja island. The present study is a continuation of previous work in an effort to confirm the practical application of Ag-ELISA in trypanosomosis control operations. Results obtained from a known tsetse and trypanosomosis-free area, on Pemba island, showed a high specificity of the test for Trypanosoma congolense, T. vivax and T. brucei. A preliminary cut-off value of 10% (Percent Positivity = PP) was used. When the PP of 10 was used on sera of trypanosomosis-endemic areas (Mangapwani, Ndijani, Dunga and Kikungwi) on Unguja island, the results reflected the `real` trypanosomis situation in the affected area. This was most strongly felt in the Mangapwani area, where tsetse and trypanosomosis were considered under control by 1994 (no tsetse flies were caught and no samples were encountered positive by the buffy coat technique). However, it should be stressed that the buffy coat technique and the Ag-ELISA complement each other and should be used in conjunction. (author). 8 refs, 1 fig., 5 tabs.

  1. Trypanosomosis surveillance on Zanzibar island, using the trypanosomal antigen detection ELISA (enzyme-linked immunosorbent assay) technique

    Mbwambo, H.A.

    1997-01-01

    The effectiveness of trypanosomosis control programs depends greatly on prior knowledge of basic data of the epidemiological situation of the disease, which in turns depends, among others, on the use of techniques that give a fairly quick and accurate diagnosis. An antigen-detection (Ag) ELISA was first introduced into Tanzania and validated at the Animal Disease Research Institute (ADRI) through the FAO/IAEA Research Contract (RC) No. 5030/NL. Incorporation of the Ag-ELISA technique into a FAO animal disease control project (1986-1993) on Unguja island, in 1992, revealed useful information of high trypanosomosis prevalence in an area previously declared free of the disease using just stained blood smears and buffy coat examinations. This triggered further efforts into more intensive surveys of the tsetse and trypanosomosis situation on Unguja island. The present study is a continuation of previous work in an effort to confirm the practical application of Ag-ELISA in trypanosomosis control operations. Results obtained from a known tsetse and trypanosomosis-free area, on Pemba island, showed a high specificity of the test for Trypanosoma congolense, T. vivax and T. brucei. A preliminary cut-off value of 10% (Percent Positivity = PP) was used. When the PP of 10 was used on sera of trypanosomosis-endemic areas (Mangapwani, Ndijani, Dunga and Kikungwi) on Unguja island, the results reflected the 'real' trypanosomis situation in the affected area. This was most strongly felt in the Mangapwani area, where tsetse and trypanosomosis were considered under control by 1994 (no tsetse flies were caught and no samples were encountered positive by the buffy coat technique). However, it should be stressed that the buffy coat technique and the Ag-ELISA complement each other and should be used in conjunction. (author). 8 refs, 1 fig., 5 tabs

  2. Comparison of enzyme-linked immunosorbent assay, radioimmunoassay, complement fixation, anticomplement immunofluorescence and passive haemaglutination techniques for detecting cytomegalovirus IgG antibody

    Booth, J C; Hannington, G; Bakir, T M.F.; Stern, H; Kangro, H; Griffiths, P D; Heath, R B [Saint George' s Hospital Medical School, London (UK); Saint Bartholomew' s Hospital, London (UK))

    1982-12-01

    The radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques were found to be comparable in sensitivity and specificity for detecting cytomegalovirus IgG antibody, and 10 to 100 times more sensitive than complement-fixation (CF), anticomplement immunofluorescence (ACIF) and passive haemagglutination (PHA). In screening tests for antibody, the frequency of false-positive and -negative results was 0.6% for RIA and ELISA, 1.5% for CF, 1.6% for ACIF and 3.6% for PHA. PHA was the least satisfactory test, largely because of technical problems.

  3. Explaining the link among self-controlling and children parenting techniques and mental insurance of high school pupils.

    Sekhavati, E; Rahimian Boogar, M; Khodadost, M; Afkari, R; Atefeh, Raoufi

    2015-01-01

    Introduction: One of the wellness estimation axes of various communities are the mental well-being of the communities. Health means an attempt to Self-actualization and development that exhibit in the adaptation of person's skills and experiences. No doubt mental health plays a major role in assuring efficiency in any organization and can be affected via different parameters. Accordingly, the current research conducted by the purpose of illustrating the relationship among self-managing and kid parenting techniques and mental health amongst high school pupils of Abadeh Town. Methodology: In this sectional-correlation research, 375 pupils are taken and involved in the research in stage group sampling technique of Abadeh high schools. Tangney's self-managing survey, Barry's kid parenting rate, Reef's mental survey and a framework of demographic data utilized to obtain data. Information investigated utilizing software SPSS 19 or Pearson's relationship coefficient analysis and stepwise multivariable regression investigation. Findings: Information investigation depicts self-managing parameter has a great and opposite predictability regarding mental health parameter (t =0.003, = β-0.158, P=2.99). Therefore self-managing has great and opposite predictability regarding 2 parts of mental health rate i.e. self-approval (P= 0.0001, t=4.87, β= - 0.181) and dominance on conditions (P= 0.0001, t=3.807, β= - 0.200). The decisions represent the proximity of a consequence relationship among predictability of kid parenting techniques regarding mental health (p=0.01, F=3.85, r2= 0.031, r=0.177). These sequences reveal great predictability of kid parenting styles in 2 various ways in 2 methods of grinding (P=0.035, t= 2.12, β=0.113) and standard (P=0.014, t=2.437, β= 0.434). The Severe method has a reversed important connection in maximum features of mental health. Furthermore, they note that "authoritative method" parameter just has prediction capacity 0.143 based on mental

  4. Explaining the link among self-controlling and children parenting techniques and mental insurance of high school pupils

    Sekhavati, E; Rahimian Boogar, M; Khodadost, M; Afkari, R; Atefeh, Raoufi

    2015-01-01

    Introduction: One of the wellness estimation axes of various communities are the mental well-being of the communities. Health means an attempt to Self-actualization and development that exhibit in the adaptation of person's skills and experiences. No doubt mental health plays a major role in assuring efficiency in any organization and can be affected via different parameters. Accordingly, the current research conducted by the purpose of illustrating the relationship among self-managing and kid parenting techniques and mental health amongst high school pupils of Abadeh Town. Methodology: In this sectional-correlation research, 375 pupils are taken and involved in the research in stage group sampling technique of Abadeh high schools. Tangney’s self-managing survey, Barry's kid parenting rate, Reef’s mental survey and a framework of demographic data utilized to obtain data. Information investigated utilizing software SPSS 19 or Pearson’s relationship coefficient analysis and stepwise multivariable regression investigation. Findings: Information investigation depicts self-managing parameter has a great and opposite predictability regarding mental health parameter (t =0.003, = β-0.158, P=2.99). Therefore self-managing has great and opposite predictability regarding 2 parts of mental health rate i.e. self-approval (P= 0.0001, t=4.87, β= - 0.181) and dominance on conditions (P= 0.0001, t=3.807, β= - 0.200). The decisions represent the proximity of a consequence relationship among predictability of kid parenting techniques regarding mental health (p=0.01, F=3.85, r2= 0.031, r=0.177). These sequences reveal great predictability of kid parenting styles in 2 various ways in 2 methods of grinding (P=0.035, t= 2.12, β=0.113) and standard (P=0.014, t=2.437, β= 0.434). The Severe method has a reversed important connection in maximum features of mental health. Furthermore, they note that "authoritative method" parameter just has prediction capacity 0.143 based on mental

  5. An overview of techniques for linking high-dimensional molecular data to time-to-event endpoints by risk prediction models.

    Binder, Harald; Porzelius, Christine; Schumacher, Martin

    2011-03-01

    Analysis of molecular data promises identification of biomarkers for improving prognostic models, thus potentially enabling better patient management. For identifying such biomarkers, risk prediction models can be employed that link high-dimensional molecular covariate data to a clinical endpoint. In low-dimensional settings, a multitude of statistical techniques already exists for building such models, e.g. allowing for variable selection or for quantifying the added value of a new biomarker. We provide an overview of techniques for regularized estimation that transfer this toward high-dimensional settings, with a focus on models for time-to-event endpoints. Techniques for incorporating specific covariate structure are discussed, as well as techniques for dealing with more complex endpoints. Employing gene expression data from patients with diffuse large B-cell lymphoma, some typical modeling issues from low-dimensional settings are illustrated in a high-dimensional application. First, the performance of classical stepwise regression is compared to stage-wise regression, as implemented by a component-wise likelihood-based boosting approach. A second issues arises, when artificially transforming the response into a binary variable. The effects of the resulting loss of efficiency and potential bias in a high-dimensional setting are illustrated, and a link to competing risks models is provided. Finally, we discuss conditions for adequately quantifying the added value of high-dimensional gene expression measurements, both at the stage of model fitting and when performing evaluation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Comparison of Intraoperatively Built Custom Linked Seeds Versus Loose Seed Gun Applicator Technique Using Real-Time Intraoperative Planning for Permanent Prostate Brachytherapy

    Zauls, A. Jason; Ashenafi, Michael S. [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC (United States); Onicescu, Georgiana [Department of Biostatistics and Epidemiology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC (United States); Clarke, Harry S. [Department of Urology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC (United States); Marshall, David T., E-mail: marshadt@musc.edu [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC (United States)

    2011-11-15

    Purpose: To report our dosimetric results using a novel push-button seed delivery system that constructs custom links of seeds intraoperatively. Methods and Materials: From 2005 to 2007, 43 patients underwent implantation using a gun applicator (GA), and from 2007 to 2008, 48 patientsunderwent implantation with a novel technique allowing creation of intraoperatively built custom links of seeds (IBCL). Specific endpoint analyses were prostate D90% (pD90%), rV100% > 1.3 cc, and overall time under anesthesia. Results: Final analyses included 91 patients, 43 GA and 48 IBCL. Absolute change in pD90% ({Delta}pD90%) between intraoperative and postoperative plans was evaluated. Using GA method, the {Delta}pD90% was -8.1Gy and -12.8Gy for I-125 and Pd-103 implants, respectively. Similarly, the IBCL technique resulted in a {Delta}pD90% of -8.7Gy and -9.8Gy for I-125 and Pd-103 implants, respectively. No statistically significant difference in {Delta}pD90% was found comparing methods. The GA method had two intraoperative and 10 postoperative rV100% >1.3 cc. For IBCL, five intraoperative and eight postoperative plans had rV100% >1.3 cc. For GA, the mean time under anesthesia was 75 min and 87 min for Pd-103 and I-125 implants, respectively. For IBCL, the mean time was 86 and 98 min for Pd-103 and I-125. There was a statistical difference between the methods when comparing mean time under anesthesia. Conclusions: Dosimetrically relevant endpoints were equivalent between the two methods. Currently, time under anesthesia is longer using the IBCL technique but has decreased over time. IBCL is a straightforward brachytherapy technique that can be implemented into clinical practice as an alternative to gun applicators.

  7. Interference Cancellation Technique Based on Discovery of Spreading Codes of Interference Signals and Maximum Correlation Detection for DS-CDMA System

    Hettiarachchi, Ranga; Yokoyama, Mitsuo; Uehara, Hideyuki

    This paper presents a novel interference cancellation (IC) scheme for both synchronous and asynchronous direct-sequence code-division multiple-access (DS-CDMA) wireless channels. In the DS-CDMA system, the multiple access interference (MAI) and the near-far problem (NFP) are the two factors which reduce the capacity of the system. In this paper, we propose a new algorithm that is able to detect all interference signals as an individual MAI signal by maximum correlation detection. It is based on the discovery of all the unknowing spreading codes of the interference signals. Then, all possible MAI patterns so called replicas are generated as a summation of interference signals. And the true MAI pattern is found by taking correlation between the received signal and the replicas. Moreover, the receiver executes MAI cancellation in a successive manner, removing all interference signals by single-stage. Numerical results will show that the proposed IC strategy, which alleviates the detrimental effect of the MAI and the near-far problem, can significantly improve the system performance. Especially, we can obtain almost the same receiving characteristics as in the absense of interference for asynchrnous system when received powers are equal. Also, the same performances can be seen under any received power state for synchronous system.

  8. Drugs + HIV, Learn the Link

    Full Text Available ... of people infected with HIV, drug misuse can interfere with an individual's likelihood of adhering to the ... HIV/AIDS and the discovery of promising treatment interventions for breaking the harmful links between them, we ...

  9. Proteomic and metabolomic approaches to biomarker discovery

    Issaq, Haleem J

    2013-01-01

    Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution.  The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis...

  10. Development of Molecular Markers Linked to Powdery Mildew Resistance Gene Pm4b by Combining SNP Discovery from Transcriptome Sequencing Data with Bulked Segregant Analysis (BSR-Seq) in Wheat.

    Wu, Peipei; Xie, Jingzhong; Hu, Jinghuang; Qiu, Dan; Liu, Zhiyong; Li, Jingting; Li, Miaomiao; Zhang, Hongjun; Yang, Li; Liu, Hongwei; Zhou, Yang; Zhang, Zhongjun; Li, Hongjie

    2018-01-01

    Powdery mildew resistance gene Pm4b , originating from Triticum persicum , is effective against the prevalent Blumeria graminis f. sp. tritici ( Bgt ) isolates from certain regions of wheat production in China. The lack of tightly linked molecular markers with the target gene prevents the precise identification of Pm4b during the application of molecular marker-assisted selection (MAS). The strategy that combines the RNA-Seq technique and the bulked segregant analysis (BSR-Seq) was applied in an F 2:3 mapping population (237 families) derived from a pair of isogenic lines VPM1/7 ∗ Bainong 3217 F 4 (carrying Pm4b ) and Bainong 3217 to develop more closely linked molecular markers. RNA-Seq analysis of the two phenotypically contrasting RNA bulks prepared from the representative F 2:3 families generated 20,745,939 and 25,867,480 high-quality read pairs, and 82.8 and 80.2% of them were uniquely mapped to the wheat whole genome draft assembly for the resistant and susceptible RNA bulks, respectively. Variant calling identified 283,866 raw single nucleotide polymorphisms (SNPs) and InDels between the two bulks. The SNPs that were closely associated with the powdery mildew resistance were concentrated on chromosome 2AL. Among the 84 variants that were potentially associated with the disease resistance trait, 46 variants were enriched in an about 25 Mb region at the distal end of chromosome arm 2AL. Four Pm4b -linked SNP markers were developed from these variants. Based on the sequences of Chinese Spring where these polymorphic SNPs were located, 98 SSR primer pairs were designed to develop distal markers flanking the Pm4b gene. Three SSR markers, Xics13 , Xics43 , and Xics76 , were incorporated in the new genetic linkage map, which located Pm4b in a 3.0 cM genetic interval spanning a 6.7 Mb physical genomic region. This region had a collinear relationship with Brachypodium distachyon chromosome 5, rice chromosome 4, and sorghum chromosome 6. Seven genes associated with

  11. Development of Molecular Markers Linked to Powdery Mildew Resistance Gene Pm4b by Combining SNP Discovery from Transcriptome Sequencing Data with Bulked Segregant Analysis (BSR-Seq in Wheat

    Peipei Wu

    2018-02-01

    Full Text Available Powdery mildew resistance gene Pm4b, originating from Triticum persicum, is effective against the prevalent Blumeria graminis f. sp. tritici (Bgt isolates from certain regions of wheat production in China. The lack of tightly linked molecular markers with the target gene prevents the precise identification of Pm4b during the application of molecular marker-assisted selection (MAS. The strategy that combines the RNA-Seq technique and the bulked segregant analysis (BSR-Seq was applied in an F2:3 mapping population (237 families derived from a pair of isogenic lines VPM1/7∗Bainong 3217 F4 (carrying Pm4b and Bainong 3217 to develop more closely linked molecular markers. RNA-Seq analysis of the two phenotypically contrasting RNA bulks prepared from the representative F2:3 families generated 20,745,939 and 25,867,480 high-quality read pairs, and 82.8 and 80.2% of them were uniquely mapped to the wheat whole genome draft assembly for the resistant and susceptible RNA bulks, respectively. Variant calling identified 283,866 raw single nucleotide polymorphisms (SNPs and InDels between the two bulks. The SNPs that were closely associated with the powdery mildew resistance were concentrated on chromosome 2AL. Among the 84 variants that were potentially associated with the disease resistance trait, 46 variants were enriched in an about 25 Mb region at the distal end of chromosome arm 2AL. Four Pm4b-linked SNP markers were developed from these variants. Based on the sequences of Chinese Spring where these polymorphic SNPs were located, 98 SSR primer pairs were designed to develop distal markers flanking the Pm4b gene. Three SSR markers, Xics13, Xics43, and Xics76, were incorporated in the new genetic linkage map, which located Pm4b in a 3.0 cM genetic interval spanning a 6.7 Mb physical genomic region. This region had a collinear relationship with Brachypodium distachyon chromosome 5, rice chromosome 4, and sorghum chromosome 6. Seven genes associated with

  12. Computational methods in drug discovery

    Sumudu P. Leelananda

    2016-12-01

    Full Text Available The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed.

  13. Design of in situ dispersible and calcium cross-linked alginate pellets as intestinal-specific drug carrier by melt pelletization technique.

    Nurulaini, Harjoh; Wong, Tin Wui

    2011-06-01

    Conventional alginate pellets underwent rapid drug dissolution and loss of multiparticulate characteristics such as aggregation in acidic medium, thereby promoting oral dose dumping. This study aimed to design sustained-release dispersible alginate pellets through rapid in situ matrix dispersion and cross-linking by calcium salts during dissolution. Pellets made of alginate and calcium salts were prepared using a solvent-free melt pelletization technique that prevented reaction between processing materials during agglomeration and allowed such a reaction to occur only in dissolution phase. Drug release was remarkably retarded in acidic medium when pellets were formulated with water-soluble calcium acetate instead of acid-soluble calcium carbonate. Different from calcium salt-free and calcium carbonate-loaded matrices that aggregated or underwent gradual erosion, rapid in situ solvation of calcium acetate in pellets during dissolution resulted in burst of gas bubbles, fast pellet breakup, and dispersion. The dispersed fragments, though exhibiting a larger specific surface area for drug dissolution than intact matrix, were rapidly cross-linked by Ca(2+) from calcium acetate and had drug release retarded till a change in medium pH from 1.2 to 6.8. Being dispersible and pH-dependent in drug dissolution, these pellets are useful as multiparticulate intestinal-specific drug carrier without exhibiting dose dumping tendency of a "single-unit-like" system via pellet aggregation. Copyright © 2011 Wiley-Liss, Inc.

  14. Discovery and characterisation of dietary patterns in two Nordic countries. Using non-supervised and supervised multivariate statistical techniques to analyse dietary survey data

    Edberg, Anna; Freyhult, Eva; Sand, Salomon

    - and inter-national data excerpts. For example, major PCA loadings helped deciphering both shared and disparate features, relating to food groups, across Danish and Swedish preschool consumers. Data interrogation, reliant on the above-mentioned composite techniques, disclosed one outlier dietary prototype...... prototype with the latter property was identified also in the Danish data material, but without low consumption of Vegetables or Fruit & berries. The second MDA-type of data interrogation involved Supervised Learning, also known as Predictive Modelling. These exercises involved the Random Forest (RF...... not elaborated on in-depth, output from several analyses suggests a preference for energy-based consumption data for Cluster Analysis and Predictive Modelling, over those appearing as weight....

  15. SVPWM Technique with Varying DC-Link Voltage for Common Mode Voltage Reduction in a Matrix Converter and Analytical Estimation of its Output Voltage Distortion

    Padhee, Varsha

    Common Mode Voltage (CMV) in any power converter has been the major contributor to premature motor failures, bearing deterioration, shaft voltage build up and electromagnetic interference. Intelligent control methods like Space Vector Pulse Width Modulation (SVPWM) techniques provide immense potential and flexibility to reduce CMV, thereby targeting all the afore mentioned problems. Other solutions like passive filters, shielded cables and EMI filters add to the volume and cost metrics of the entire system. Smart SVPWM techniques therefore, come with a very important advantage of being an economical solution. This thesis discusses a modified space vector technique applied to an Indirect Matrix Converter (IMC) which results in the reduction of common mode voltages and other advanced features. The conventional indirect space vector pulse-width modulation (SVPWM) method of controlling matrix converters involves the usage of two adjacent active vectors and one zero vector for both rectifying and inverting stages of the converter. By suitable selection of space vectors, the rectifying stage of the matrix converter can generate different levels of virtual DC-link voltage. This capability can be exploited for operation of the converter in different ranges of modulation indices for varying machine speeds. This results in lower common mode voltage and improves the harmonic spectrum of the output voltage, without increasing the number of switching transitions as compared to conventional modulation. To summarize it can be said that the responsibility of formulating output voltages with a particular magnitude and frequency has been transferred solely to the rectifying stage of the IMC. Estimation of degree of distortion in the three phase output voltage is another facet discussed in this thesis. An understanding of the SVPWM technique and the switching sequence of the space vectors in detail gives the potential to estimate the RMS value of the switched output voltage of any

  16. Evaluation of laser diode thermal desorption (LDTD) coupled with tandem mass spectrometry (MS/MS) for support of in vitro drug discovery assays: increasing scope, robustness and throughput of the LDTD technique for use with chemically diverse compound libraries.

    Beattie, Iain; Smith, Aaron; Weston, Daniel J; White, Peter; Szwandt, Simon; Sealey, Laura

    2012-02-05

    Within the drug discovery environment, the key process in optimising the chemistry of a structural series toward a potential drug candidate is the design, make and test cycle, in which the primary screens consist of a number of in vitro assays, including metabolic stability, cytochrome P450 inhibition, and time-dependent inhibition assays. These assays are often carried out using multiple drug compounds with chemically diverse structural features, often in a 96 well-plate format for maximum time-efficiency, and are supported using rapid liquid chromatographic (LC) sample introduction with a tandem mass spectrometry (MS/MS) selected reaction monitoring (SRM) endpoint, taking around 6.5 h per plate. To provide a faster time-to-decision at this critical point, there exists a requirement for higher sample throughput and a robust, well-characterized analytical alternative. This paper presents a detailed evaluation of laser diode thermal desorption (LDTD), a relatively new ambient sample ionization technique, for compound screening assays. By systematic modification of typical LDTD instrumentation and workflow, and providing deeper understanding around overcoming a number of key issues, this work establishes LDTD as a practical, rapid alternative to conventional LC-MS/MS in drug discovery, without need for extensive sample preparation or expensive, scope-limiting internal standards. Analysis of both the five and three cytochrome P450 competitive inhibition assay samples by LDTD gave improved sample throughput (0.75 h per plate) and provided comparable data quality as the IC₅₀ values obtained were within 3 fold of those calculated from the LC-MS/MS data. Additionally when applied generically to a chemically diverse library of over 250 proprietary compounds from the AstraZeneca design, make and test cycle, LDTD demonstrated a success rate of 98%. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Deep Learning in Drug Discovery.

    Gawehn, Erik; Hiss, Jan A; Schneider, Gisbert

    2016-01-01

    Artificial neural networks had their first heyday in molecular informatics and drug discovery approximately two decades ago. Currently, we are witnessing renewed interest in adapting advanced neural network architectures for pharmaceutical research by borrowing from the field of "deep learning". Compared with some of the other life sciences, their application in drug discovery is still limited. Here, we provide an overview of this emerging field of molecular informatics, present the basic concepts of prominent deep learning methods and offer motivation to explore these techniques for their usefulness in computer-assisted drug discovery and design. We specifically emphasize deep neural networks, restricted Boltzmann machine networks and convolutional networks. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. New Approaches to the Sea-Floor Mapping: Results From the GEBCO-NF Alumni Team's Technique Developments in Preparation to the Shell Ocean Discovery XPRIZE 2017.

    Bazhenova, E.; Zarayskaya, Y.; Wigley, R. A.; Anderson, R.; Falconer, R. K. H.; Kearns, T.; Martin, T.; Minami, H.; Roperez, J.; Rosedee, A.; Sade, H.; Seeboruth, S.; Simpson, B.; Sumiyoshi, M.; Tinmouth, N.; Zwolak, K.

    2017-12-01

    In preparation for the XPRIZE 2017 Round 1, a new sea-floor mapping system has been assembled based on an Unmanned Surface Vessel (USV) coupled with an Autonomous Underwater Vehicle (AUV). USV operation allows reducing logistics costs, while the AUV provides enhanced maneuverability and high accuracy of stabilization for the mapping missions. The AUV is equipped with a high-resolution interferometric synthetic aperture sonar (HISAS) and a multibeam sonar (MBES), covering a wide bathymetry swath and the nadir, respectively. Typically operating at 20 to 40 m altitude, the HISAS is capable of providing SAS imagery with 4 x 4 cm resolution and bathymetry with 40 x 40 cm resolution throughout the swath. Smaller areas of interest (50 x 50 m) can be further examined using the Spot processing technique, to produce SAS imagery with 2 x 2 cm resolution and high- resolution SAS bathymetry with 5 x 5 cm resolution. This allows multi-aspect imaging and examination of seabed geological features at different scales. Advanced data post-processing can be performed to produce 3D images of objects and explore their structure using the shadow contrast and shape. Being an interferometric system, the HISAS collects data for both imagery and bathymetry in the same swath. This improves the robustness for SAS in areas with significant relief. In the standard survey mode, the HISAS can typically collect SAS data at 2.6 km2/hr over relatively flat ground. Another limiting factor to the HISAS data coverage and quality is the vehicle stability influenced by downslope and cross currents and the resulting vehicle's speed. From experience, the best coverage occurs at a vehicle speed of around 2 m/s. At slower speeds the vehicle starts to lose steerage leading to degradation of tracking and navigation performance, which harms the focusing algorithm that creates the SAS data. For the AUV mission planning in unknown areas or in case of highly variable conditions at the study site, MBES

  19. Drugs + HIV, Learn the Link

    Full Text Available ... projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and ... HIV/AIDS and the discovery of promising treatment interventions for breaking the harmful links between them, we ...

  20. Synthesis of an oxytetracyline-tolidin-BSA immunogen and antibodies production of anti-oxytetracyline developed for oxytetracyline residue detection with enzyme-linked immunosorbent assays technique

    Widiastuti R

    2013-06-01

    Full Text Available An oxytetracycline-tolidin-bovine serum albumin (OTC-tolidin-BSA-conjugate was synthezed as immunogen for producing specific antibodies in immunized rabbits that would be used as reagent for development of OTC residue detection with enzym-linked immunoassays technique. The immunogen was prepared through diazotization tolidin and subsequently reacted with OTC. The red purple immunogen of OTC-tolidin-BSA absorbed at wave lengths of 277 nm and 488 nm under UV screening absorbances and confirmation with the high performance liquid chromatography (HPLC showed the absence of peak at retention time of 3.46 minutes. Characaterized result with SDS-PAGE showed the molecular weight of the OTC-tolidin-BSA at 69.79 kDA. Subsequently, the immunogen was immunized into New Zealand rabbits in order to produce the polyclonal antibodies. The antibodies were purified using a protein A sepharose column. The OD optimum responses of 0.92 to 1.20 were obtained from the second fractionation at dilution of 1/1000 by titrating the antibodies and OTC-tolidin-BSA coating antigen at concentration of 10 µg/mL on several bleeding times.

  1. Linked data management

    Hose, Katja; Schenkel, Ralf

    2014-01-01

    Linked Data Management presents techniques for querying and managing Linked Data that is available on today’s Web. The book shows how the abundance of Linked Data can serve as fertile ground for research and commercial applications. The text focuses on aspects of managing large-scale collections of Linked Data. It offers a detailed introduction to Linked Data and related standards, including the main principles distinguishing Linked Data from standard database technology. Chapters also describe how to generate links between datasets and explain the overall architecture of data integration systems based on Linked Data. A large part of the text is devoted to query processing in different setups. After presenting methods to publish relational data as Linked Data and efficient centralized processing, the book explores lookup-based, distributed, and parallel solutions. It then addresses advanced topics, such as reasoning, and discusses work related to read-write Linked Data for system interoperation. Desp...

  2. Usability of Discovery Portals

    Bulens, J.D.; Vullings, L.A.E.; Houtkamp, J.M.; Vanmeulebrouk, B.

    2013-01-01

    As INSPIRE progresses to be implemented in the EU, many new discovery portals are built to facilitate finding spatial data. Currently the structure of the discovery portals is determined by the way spatial data experts like to work. However, we argue that the main target group for discovery portals are not spatial data experts but professionals with limited spatial knowledge, and a focus outside the spatial domain. An exploratory usability experiment was carried out in which three discovery p...

  3. Usability of Discovery Portals

    Bulens, J.D.; Vullings, L.A.E.; Houtkamp, J.M.; Vanmeulebrouk, B.

    2013-01-01

    As INSPIRE progresses to be implemented in the EU, many new discovery portals are built to facilitate finding spatial data. Currently the structure of the discovery portals is determined by the way spatial data experts like to work. However, we argue that the main target group for discovery portals

  4. Discovery and the atom

    1989-01-01

    ''Discovery and the Atom'' tells the story of the founding of nuclear physics. This programme looks at nuclear physics up to the discovery of the neutron in 1932. Animation explains the science of the classic experiments, such as the scattering of alpha particles by Rutherford and the discovery of the nucleus. Archive film shows the people: Lord Rutherford, James Chadwick, Marie Curie. (author)

  5. Final Progress Report submitted via the DOE Energy Link (E-Link) in June 2009 [Collaborative Research: Decadal-to-Centennial Climate & Climate Change Studies with Enhanced Variable and Uniform Resolution GCMs Using Advanced Numerical Techniques

    Fox-Rabinovitz, Michael S. [Univ. of Quebec (Canada); Cote, Jean [Univ. of Quebec (Canada)

    2009-10-09

    The joint U.S-Canadian project has been devoted to: (a) decadal climate studies using developed state-of-the-art GCMs (General Circulation Models) with enhanced variable and uniform resolution; (b) development and implementation of advanced numerical techniques; (c) research in parallel computing and associated numerical methods; (d) atmospheric chemistry experiments related to climate issues; (e) validation of regional climate modeling strategies for nested- and stretched-grid models. The variable-resolution stretched-grid (SG) GCMs produce accurate and cost-efficient regional climate simulations with mesoscale resolution. The advantage of the stretched grid approach is that it allows us to preserve the high quality of both global and regional circulations while providing consistent interactions between global and regional scales and phenomena. The major accomplishment for the project has been the successful international SGMIP-1 and SGMIP-2 (Stretched-Grid Model Intercomparison Project, phase-1 and phase-2) based on this research developments and activities. The SGMIP provides unique high-resolution regional and global multi-model ensembles beneficial for regional climate modeling and broader modeling community. The U.S SGMIP simulations have been produced using SciDAC ORNL supercomputers. The results of the successful SGMIP multi-model ensemble simulations of the U.S. climate are available at the SGMIP web site (http://essic.umd.edu/~foxrab/sgmip.html) and through the link to the WMO/WCRP/WGNE web site: http://collaboration.cmc.ec.gc.ca/science/wgne. Collaborations with other international participants M. Deque (Meteo-France) and J. McGregor (CSIRO, Australia) and their centers and groups have been beneficial for the strong joint effort, especially for the SGMIP activities. The WMO/WCRP/WGNE endorsed the SGMIP activities in 2004-2008. This project reflects a trend in the modeling and broader communities to move towards regional and sub-regional assessments and

  6. A Technique Socratic Questioning-Guided Discovery

    M. Hakan Türkçapar; A. Emre Sargýn

    2012-01-01

    “Socratic Method” is a way of teaching philosophical thinking and knowledge by asking questions which was used by antique period greek philosopher Socrates. Socrates was teaching knowledge to his followers by asking questions and the conversation between them was named “Socratic Dialogues”. In this meaning, no novel knowledge is taught to the individual but only what is formerly known is reminded and rediscovered. The form of socratic questioning which is used during t...

  7. Web-based services for drug design and discovery.

    Frey, Jeremy G; Bird, Colin L

    2011-09-01

    Reviews of the development of drug discovery through the 20(th) century recognised the importance of chemistry and increasingly bioinformatics, but had relatively little to say about the importance of computing and networked computing in particular. However, the design and discovery of new drugs is arguably the most significant single application of bioinformatics and cheminformatics to have benefitted from the increases in the range and power of the computational techniques since the emergence of the World Wide Web, commonly now referred to as simply 'the Web'. Web services have enabled researchers to access shared resources and to deploy standardized calculations in their search for new drugs. This article first considers the fundamental principles of Web services and workflows, and then explores the facilities and resources that have evolved to meet the specific needs of chem- and bio-informatics. This strategy leads to a more detailed examination of the basic components that characterise molecules and the essential predictive techniques, followed by a discussion of the emerging networked services that transcend the basic provisions, and the growing trend towards embracing modern techniques, in particular the Semantic Web. In the opinion of the authors, the issues that require community action are: increasing the amount of chemical data available for open access; validating the data as provided; and developing more efficient links between the worlds of cheminformatics and bioinformatics. The goal is to create ever better drug design services.

  8. Topology Discovery Using Cisco Discovery Protocol

    Rodriguez, Sergio R.

    2009-01-01

    In this paper we address the problem of discovering network topology in proprietary networks. Namely, we investigate topology discovery in Cisco-based networks. Cisco devices run Cisco Discovery Protocol (CDP) which holds information about these devices. We first compare properties of topologies that can be obtained from networks deploying CDP versus Spanning Tree Protocol (STP) and Management Information Base (MIB) Forwarding Database (FDB). Then we describe a method of discovering topology ...

  9. Discovery Mondays: Surveyors' Tools

    2003-01-01

    Surveyors of all ages, have your rulers and compasses at the ready! This sixth edition of Discovery Monday is your chance to learn about the surveyor's tools - the state of the art in measuring instruments - and see for yourself how they work. With their usual daunting precision, the members of CERN's Surveying Group have prepared some demonstrations and exercises for you to try. Find out the techniques for ensuring accelerator alignment and learn about high-tech metrology systems such as deviation indicators, tracking lasers and total stations. The surveyors will show you how they precisely measure magnet positioning, with accuracy of a few thousandths of a millimetre. You can try your hand at precision measurement using different types of sensor and a modern-day version of the Romans' bubble level, accurate to within a thousandth of a millimetre. You will learn that photogrammetry techniques can transform even a simple digital camera into a remarkable measuring instrument. Finally, you will have a chance t...

  10. Applied metabolomics in drug discovery.

    Cuperlovic-Culf, M; Culf, A S

    2016-08-01

    The metabolic profile is a direct signature of phenotype and biochemical activity following any perturbation. Metabolites are small molecules present in a biological system including natural products as well as drugs and their metabolism by-products depending on the biological system studied. Metabolomics can provide activity information about possible novel drugs and drug scaffolds, indicate interesting targets for drug development and suggest binding partners of compounds. Furthermore, metabolomics can be used for the discovery of novel natural products and in drug development. Metabolomics can enhance the discovery and testing of new drugs and provide insight into the on- and off-target effects of drugs. This review focuses primarily on the application of metabolomics in the discovery of active drugs from natural products and the analysis of chemical libraries and the computational analysis of metabolic networks. Metabolomics methodology, both experimental and analytical is fast developing. At the same time, databases of compounds are ever growing with the inclusion of more molecular and spectral information. An increasing number of systems are being represented by very detailed metabolic network models. Combining these experimental and computational tools with high throughput drug testing and drug discovery techniques can provide new promising compounds and leads.

  11. Beyond information retrieval: information discovery and multimedia information retrieval

    Roberto Raieli

    2017-01-01

    The paper compares the current methodologies for search and discovery of information and information resources: terminological search and term-based language, own of information retrieval (IR); semantic search and information discovery, being developed mainly through the language of linked data; semiotic search and content-based language, experienced by multimedia information retrieval (MIR).MIR semiotic methodology is, then, detailed.

  12. Sparse Mbplsr for Metabolomics Data and Biomarker Discovery

    Karaman, İbrahim

    2014-01-01

    the link between high throughput metabolomics data generated on different analytical platforms, discover important metabolites deriving from the digestion processes in the gut, and automate metabolic pathway discovery from mass spectrometry. PLS (partial least squares) based chemometric methods were...

  13. Service Discovery At Home

    Sundramoorthy, V.; Scholten, Johan; Jansen, P.G.; Hartel, Pieter H.

    Service discovery is a fady new field that kicked off since the advent of ubiquitous computing and has been found essential in the making of intelligent networks by implementing automated discovery and remote control between deviies. This paper provides an ovewiew and comparison of several prominent

  14. Academic Drug Discovery Centres

    Kirkegaard, Henriette Schultz; Valentin, Finn

    2014-01-01

    Academic drug discovery centres (ADDCs) are seen as one of the solutions to fill the innovation gap in early drug discovery, which has proven challenging for previous organisational models. Prior studies of ADDCs have identified the need to analyse them from the angle of their economic...

  15. Decades of Discovery

    2011-06-01

    For the past two-and-a-half decades, the Office of Science at the U.S. Department of Energy has been at the forefront of scientific discovery. Over 100 important discoveries supported by the Office of Science are represented in this document.

  16. Service discovery at home

    Sundramoorthy, V.; Scholten, Johan; Jansen, P.G.; Hartel, Pieter H.

    2003-01-01

    Service discovery is a fairly new field that kicked off since the advent of ubiquitous computing and has been found essential in the making of intelligent networks by implementing automated discovery and remote control between devices. This paper provides an overview and comparison of several

  17. "Eureka, Eureka!" Discoveries in Science

    Agarwal, Pankaj

    2011-01-01

    Accidental discoveries have been of significant value in the progress of science. Although accidental discoveries are more common in pharmacology and chemistry, other branches of science have also benefited from such discoveries. While most discoveries are the result of persistent research, famous accidental discoveries provide a fascinating…

  18. From the nucleus discovery to DWBA

    Fernandez, B.

    2007-01-01

    The author presents a brief review of the main events in the field of nuclear reactions that are acknowledged as milestones because of their importance due to either experimental setting or physical interpretation. It is shown that the pace of discoveries has been strongly dependent on the technical progress in detection means at the beginning of nuclear physics and now is linked to the development of simulation means. The discovery of the neutron, the development of the Geiger counter, the theory of the compound nucleus or the first direct reactions are among these milestones

  19. The Greatest Mathematical Discovery?

    Bailey, David H.; Borwein, Jonathan M.

    2010-05-12

    What mathematical discovery more than 1500 years ago: (1) Is one of the greatest, if not the greatest, single discovery in the field of mathematics? (2) Involved three subtle ideas that eluded the greatest minds of antiquity, even geniuses such as Archimedes? (3) Was fiercely resisted in Europe for hundreds of years after its discovery? (4) Even today, in historical treatments of mathematics, is often dismissed with scant mention, or else is ascribed to the wrong source? Answer: Our modern system of positional decimal notation with zero, together with the basic arithmetic computational schemes, which were discovered in India about 500 CE.

  20. Discovery of natural resources

    Guild, P.W.

    1976-01-01

    Mankind will continue to need ores of more or less the types and grades used today to supply its needs for new mineral raw materials, at least until fusion or some other relatively cheap, inexhaustible energy source is developed. Most deposits being mined today were exposed at the surface or found by relatively simple geophysical or other prospecting techniques, but many of these will be depleted in the foreseeable future. The discovery of deeper or less obvious deposits to replace them will require the conjunction of science and technology to deduce the laws that governed the concentration of elements into ores and to detect and evaluate the evidence of their whereabouts. Great theoretical advances are being made to explain the origins of ore deposits and understand the general reasons for their localization. These advances have unquestionable value for exploration. Even a large deposit is, however, very small, and, with few exceptions, it was formed under conditions that have long since ceased to exist. The explorationist must suppress a great deal of "noise" to read and interpret correctly the "signals" that can define targets and guide the drilling required to find it. Is enough being done to ensure the long-term availability of mineral raw materials? The answer is probably no, in view of the expanding consumption and the difficulty of finding new deposits, but ingenuity, persistence, and continued development of new methods and tools to add to those already at hand should put off the day of "doing without" for many years. The possibility of resource exhaustion, especially in view of the long and increasing lead time needed to carry out basic field and laboratory studies in geology, geophysics, and geochemistry and to synthesize and analyze the information gained from them counsels against any letting down of our guard, however (17). Research and exploration by government, academia, and industry must be supported and encouraged; we cannot wait until an eleventh

  1. Supernovae Discovery Efficiency

    John, Colin

    2018-01-01

    Abstract:We present supernovae (SN) search efficiency measurements for recent Hubble Space Telescope (HST) surveys. Efficiency is a key component to any search, and is important parameter as a correction factor for SN rates. To achieve an accurate value for efficiency, many supernovae need to be discoverable in surveys. This cannot be achieved from real SN only, due to their scarcity, so fake SN are planted. These fake supernovae—with a goal of realism in mind—yield an understanding of efficiency based on position related to other celestial objects, and brightness. To improve realism, we built a more accurate model of supernovae using a point-spread function. The next improvement to realism is planting these objects close to galaxies and of various parameters of brightness, magnitude, local galactic brightness and redshift. Once these are planted, a very accurate SN is visible and discoverable by the searcher. It is very important to find factors that affect this discovery efficiency. Exploring the factors that effect detection yields a more accurate correction factor. Further inquires into efficiency give us a better understanding of image processing, searching techniques and survey strategies, and result in an overall higher likelihood to find these events in future surveys with Hubble, James Webb, and WFIRST telescopes. After efficiency is discovered and refined with many unique surveys, it factors into measurements of SN rates versus redshift. By comparing SN rates vs redshift against the star formation rate we can test models to determine how long star systems take from the point of inception to explosion (delay time distribution). This delay time distribution is compared to SN progenitors models to get an accurate idea of what these stars were like before their deaths.

  2. Discovery of the neutron (to the fiftieth anniversary of neutron discovery)

    Pasechnik, M.V.

    1984-01-01

    Development of neutron physics in the USSR for the recent 50 years from the moment of neutron discovery is considered. History of neutron discovery is presented in brief. Neutron properties and fundamental problems of physics: electric dipole neutron moment, neutron β-decay, neutron interaction with nuclei and potential of nucleon interaction not conserving spatial parity are discussed. Main aspects of neutron physics application in power engineering, nuclear technology and other branches of science and technique are set forth

  3. Fateful discovery almost forgotten

    1989-01-01

    "The discovery of the fission of uranium exactly half a century ago is at risk of passing unremarked because of the general ambivalence towards the consequences of this development. Can that be wise?" (4 pages)

  4. Toxins and drug discovery.

    Harvey, Alan L

    2014-12-15

    Components from venoms have stimulated many drug discovery projects, with some notable successes. These are briefly reviewed, from captopril to ziconotide. However, there have been many more disappointments on the road from toxin discovery to approval of a new medicine. Drug discovery and development is an inherently risky business, and the main causes of failure during development programmes are outlined in order to highlight steps that might be taken to increase the chances of success with toxin-based drug discovery. These include having a clear focus on unmet therapeutic needs, concentrating on targets that are well-validated in terms of their relevance to the disease in question, making use of phenotypic screening rather than molecular-based assays, and working with development partners with the resources required for the long and expensive development process. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  5. Defining Creativity with Discovery

    Wilson, Nicholas Charles; Martin, Lee

    2017-01-01

    The standard definition of creativity has enabled significant empirical and theoretical advances, yet contains philosophical conundrums concerning the nature of novelty and the role of recognition and values. In this work we offer an act of conceptual valeting that addresses these issues and in doing so, argue that creativity definitions can be extended through the use of discovery. Drawing on dispositional realist philosophy we outline why adding the discovery and bringing into being of new ...

  6. On the antiproton discovery

    Piccioni, O.

    1989-01-01

    The author of this article describes his own role in the discovery of the antiproton. Although Segre and Chamberlain received the Nobel Prize in 1959 for its discovery, the author claims that their experimental method was his idea which he communicated to them informally in December 1954. He describes how his application for citizenship (he was Italian), and other scientists' manipulation, prevented him from being at Berkeley to work on the experiment himself. (UK)

  7. Discovery Driven Growth

    Bukh, Per Nikolaj

    2009-01-01

    Anmeldelse af Discovery Driven Growh : A breakthrough process to reduce risk and seize opportunity, af Rita G. McGrath & Ian C. MacMillan, Boston: Harvard Business Press. Udgivelsesdato: 14 august......Anmeldelse af Discovery Driven Growh : A breakthrough process to reduce risk and seize opportunity, af Rita G. McGrath & Ian C. MacMillan, Boston: Harvard Business Press. Udgivelsesdato: 14 august...

  8. The π discovery

    Fowler, P.H.

    1988-01-01

    The paper traces the discovery of the Π meson. The discovery was made by exposure of nuclear emulsions to cosmic radiation at high altitudes, with subsequent scanning of the emulsions for meson tracks. Disintegration of nuclei by a negative meson, and the decay of a Π meson were both observed. Further measurements revealed the mass of the meson. The studies carried out on the origin of the Π-mesons, and their mode of decay, are both described. (U.K.)

  9. Computational discovery of picomolar Q(o) site inhibitors of cytochrome bc1 complex.

    Hao, Ge-Fei; Wang, Fu; Li, Hui; Zhu, Xiao-Lei; Yang, Wen-Chao; Huang, Li-Shar; Wu, Jia-Wei; Berry, Edward A; Yang, Guang-Fu

    2012-07-11

    A critical challenge to the fragment-based drug discovery (FBDD) is its low-throughput nature due to the necessity of biophysical method-based fragment screening. Herein, a method of pharmacophore-linked fragment virtual screening (PFVS) was successfully developed. Its application yielded the first picomolar-range Q(o) site inhibitors of the cytochrome bc(1) complex, an important membrane protein for drug and fungicide discovery. Compared with the original hit compound 4 (K(i) = 881.80 nM, porcine bc(1)), the most potent compound 4f displayed 20 507-fold improved binding affinity (K(i) = 43.00 pM). Compound 4f was proved to be a noncompetitive inhibitor with respect to the substrate cytochrome c, but a competitive inhibitor with respect to the substrate ubiquinol. Additionally, we determined the crystal structure of compound 4e (K(i) = 83.00 pM) bound to the chicken bc(1) at 2.70 Å resolution, providing a molecular basis for understanding its ultrapotency. To our knowledge, this study is the first application of the FBDD method in the discovery of picomolar inhibitors of a membrane protein. This work demonstrates that the novel PFVS approach is a high-throughput drug discovery method, independent of biophysical screening techniques.

  10. Big Data in Drug Discovery.

    Brown, Nathan; Cambruzzi, Jean; Cox, Peter J; Davies, Mark; Dunbar, James; Plumbley, Dean; Sellwood, Matthew A; Sim, Aaron; Williams-Jones, Bryn I; Zwierzyna, Magdalena; Sheppard, David W

    2018-01-01

    Interpretation of Big Data in the drug discovery community should enhance project timelines and reduce clinical attrition through improved early decision making. The issues we encounter start with the sheer volume of data and how we first ingest it before building an infrastructure to house it to make use of the data in an efficient and productive way. There are many problems associated with the data itself including general reproducibility, but often, it is the context surrounding an experiment that is critical to success. Help, in the form of artificial intelligence (AI), is required to understand and translate the context. On the back of natural language processing pipelines, AI is also used to prospectively generate new hypotheses by linking data together. We explain Big Data from the context of biology, chemistry and clinical trials, showcasing some of the impressive public domain sources and initiatives now available for interrogation. © 2018 Elsevier B.V. All rights reserved.

  11. High-performance thin-layer chromatography linked with (bio)assays and mass spectrometry - a suited method for discovery and quantification of bioactive components? Exemplarily shown for turmeric and milk thistle extracts.

    Taha, Mahmoud N; Krawinkel, Michael B; Morlock, Gertrud E

    2015-05-15

    Extraction parameters, chemical fingerprint, and the single compounds' activity levels were considered for the selection of active botanicals. For an initial survey, the total bioactivity (i.e., total reducing capacity, total flavonoids contents and free radical scavenging capacity) of 21 aqueous and 21 ethanolic plant extracts was investigated. Ethanolic extracts showed a higher yield and were further analyzed by HPTLC in detail to obtain fingerprints of single flavonoids and further bioactive components. Exemplarily shown for turmeric (Curcuma longa) and milk thistle (Silybum marianum), effect-directed analysis (EDA) was performed using three selected (bio)assays, the Aliivibrio fischeri bioassay, the Bacillus subtilis bioassay and the 2,2-diphenyl-1-picrylhydrazyl (DPPH*) assay. As a proof of principle, the bioactive components found in the extracts were confirmed by HPTLC-MS. Bioassays in combination with planar chromatography directly linked to the known, single effective compounds like curcumin and silibinin. However, also some unknown bioactive components were discovered and exemplarily characterized, which demonstrated the strength of this kind of EDA. HPTLC-UV/Vis/FLD-EDA-MS could become a useful tool for selection of active botanicals and for the activity profiling of the active ingredients therein. The flexibility in effect-directed detections allows a comprehensive survey of effective ingredients in samples. This streamlined methodology comprised a non-targeted, effect-directed screening first, followed by a highly targeted characterization of the discovered bioactive compounds. HPTLC-EDA-MS can also be recommended for bioactivity profiling of food on the food intake side, as not only effective phytochemicals, but also unknown bioactive degradation products during food processing or contamination products or residues or metabolites can be detected. Thus, an efficient survey on potential food intake effects on wellness could be obtained. Having performed

  12. Polonium: 110th anniversary of its discovery

    Mould, R. F.

    2008-01-01

    It is appropriate that the 110 Th anniversary of the discovery of polonium by Marie and Pierre Curie is commemorated in a Polish journal since this element was named for Poland and was also the element discovered by the Curies before they discovered radium. Polonium's discovery and characteristics are described. Polonium has never been used in medicine, and was largely forgotten apart from a few minor industrial uses, and as a trigger for a nuclear weapon, until the murder in November 2006 in London using 210 Polonium, of the ex-KGB officer Alexander Litvinenko. Polonium had previously been linked, without any definite proof, with the deaths of a few scientists who had worked with the element, including Irene and Frederick Joliet-Curie. This review ends with possible evidence for such links. (authors)

  13. Cancer Biomarker Discovery: Lectin-Based Strategies Targeting Glycoproteins

    David Clark

    2012-01-01

    Full Text Available Biomarker discovery can identify molecular markers in various cancers that can be used for detection, screening, diagnosis, and monitoring of disease progression. Lectin-affinity is a technique that can be used for the enrichment of glycoproteins from a complex sample, facilitating the discovery of novel cancer biomarkers associated with a disease state.

  14. DB-XES : enabling process discovery in the large

    Syamsiyah, A.; van Dongen, B.F.; van der Aalst, W.M.P.; Ceravolo, P.; Guetl, C.; Rinderle-Ma, S.

    2018-01-01

    Dealing with the abundance of event data is one of the main process discovery challenges. Current process discovery techniques are able to efficiently handle imported event log files that fit in the computer’s memory. Once data files get bigger, scalability quickly drops since the speed required to

  15. The centenary of discovery of radium

    Mazeron, J.-J.; Gerbaulet, A.

    1998-01-01

    Henri Becquerel presented the discovery of radium by Pierre and Marie Curie at the Paris Academy of Science on 26th December 1898. One century later, radium has been abandoned, mainly for radiation protection difficulties. It is, however, likely that modern techniques of brachytherapy have inherited to those designed for radium sources, and that radium has cured thousands and thousands patients all over the world for about eighty years. The history of discovery and medical use of radium is summarised. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  16. Computational neuropharmacology: dynamical approaches in drug discovery.

    Aradi, Ildiko; Erdi, Péter

    2006-05-01

    Computational approaches that adopt dynamical models are widely accepted in basic and clinical neuroscience research as indispensable tools with which to understand normal and pathological neuronal mechanisms. Although computer-aided techniques have been used in pharmaceutical research (e.g. in structure- and ligand-based drug design), the power of dynamical models has not yet been exploited in drug discovery. We suggest that dynamical system theory and computational neuroscience--integrated with well-established, conventional molecular and electrophysiological methods--offer a broad perspective in drug discovery and in the search for novel targets and strategies for the treatment of neurological and psychiatric diseases.

  17. Operative Links

    Wistoft, Karen; Højlund, Holger

    2012-01-01

    educational goals, learning content, or value clarification. Health pedagogy is often a matter of retrospective rationalization rather than the starting point of planning. Health and risk behaviour approaches override health educational approaches. Conclusions: Operational links between health education......, health professionalism, and management strategies pose the foremost challenge. Operational links indicates cooperative levels that facilitate a creative and innovative effort across traditional professional boundaries. It is proposed that such links are supported by network structures, shared semantics...

  18. Discovery of charm

    Goldhaber, G.

    1984-11-01

    In my talk I will cover the period 1973 to 1976 which saw the discoveries of the J/psi and psi' resonances and most of the Psion spectroscopy, the tau lepton and the D 0 ,D + charmed meson doublet. Occasionally I will refer briefly to more recent results. Since this conference is on the history of the weak-interactions I will deal primarily with the properties of naked charm and in particular the weakly decaying doublet of charmed mesons. Most of the discoveries I will mention were made with the SLAC-LBL Magnetic Detector or MARK I which we operated at SPEAR from 1973 to 1976. 27 references

  19. Discovery in a World of Mashups

    King, T. A.; Ritschel, B.; Hourcle, J. A.; Moon, I. S.

    2014-12-01

    When the first digital information was stored electronically, discovery of what existed was through file names and the organization of the file system. With the advent of networks, digital information was shared on a wider scale, but discovery remained based on file and folder names. With a growing number of information sources, named based discovery quickly became ineffective. The keyword based search engine was one of the first types of a mashup in the world of Web 1.0. Embedded links from one document to another with prescribed relationships between files and the world of Web 2.0 was formed. Search engines like Google used the links to improve search results and a worldwide mashup was formed. While a vast improvement, the need for semantic (meaning rich) discovery was clear, especially for the discovery of scientific data. In response, every science discipline defined schemas to describe their type of data. Some core schemas where shared, but most schemas are custom tailored even though they share many common concepts. As with the networking of information sources, science increasingly relies on data from multiple disciplines. So there is a need to bring together multiple sources of semantically rich information. We explore how harvesting, conceptual mapping, facet based search engines, search term promotion, and style sheets can be combined to create the next generation of mashups in the emerging world of Web 3.0. We use NASA's Planetary Data System and NASA's Heliophysics Data Environment to illustrate how to create a multi-discipline mash-up.

  20. High throughput electrophysiology: new perspectives for ion channel drug discovery

    Willumsen, Niels J; Bech, Morten; Olesen, Søren-Peter

    2003-01-01

    . A cornerstone in current drug discovery is high throughput screening assays which allow examination of the activity of specific ion channels though only to a limited extent. Conventional patch clamp remains the sole technique with sufficiently high time resolution and sensitivity required for precise and direct....... The introduction of new powerful HTS electrophysiological techniques is predicted to cause a revolution in ion channel drug discovery....

  1. Discovery: Pile Patterns

    de Mestre, Neville

    2017-01-01

    Earlier "Discovery" articles (de Mestre, 1999, 2003, 2006, 2010, 2011) considered patterns from many mathematical situations. This article presents a group of patterns used in 19th century mathematical textbooks. In the days of earlier warfare, cannon balls were stacked in various arrangements depending on the shape of the pile base…

  2. Discovery and Innovation

    Discovery and Innovation is a journal of the African Academy of Sciences (AAS) ... World (TWAS) meant to focus attention on science and technology in Africa and the ... of Non-wood Forest Products: Potential Impacts and Challenges in Africa ...

  3. Discovery of TUG-770

    Christiansen, Elisabeth; Hansen, Steffen V F; Urban, Christian

    2013-01-01

    Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical...

  4. The discovery of fission

    McKay, H.A.C.

    1978-01-01

    In this article by the retired head of the Separation Processes Group of the Chemistry Division, Atomic Energy Research Establishment, Harwell, U.K., the author recalls what he terms 'an exciting drama, the unravelling of the nature of the atomic nucleus' in the years before the Second World War, including the discovery of fission. 12 references. (author)

  5. The Discovery of America

    Martin, Paul S.

    1973-01-01

    Discusses a model for explaining the spread of human population explosion on North American continent since its discovery 12,000 years ago. The model may help to map the spread of Homo sapiens throughout the New World by using the extinction chronology of the Pleistocene megafauna. (Author/PS)

  6. Predictors of timing of pregnancy discovery.

    McCarthy, Molly; Upadhyay, Ushma; Biggs, M Antonia; Anthony, Renaisa; Holl, Jennifer; Roberts, Sarah Cm

    2018-04-01

    Earlier pregnancy discovery is important in the context of prenatal and abortion care. We evaluated characteristics associated with later pregnancy discovery among women seeking abortion care. Data come from a survey of women seeking abortion care at four family planning facilities in Utah. The participants completed a survey during the state-mandated abortion information visit they are required to complete prior to having an abortion. The outcome in this study was pregnancy discovery before versus after 6 weeks since respondents' last menstrual period (LMP). We used logistic regression to estimate the relationship between sociodemographic and health-related independent variables of interest and pregnancy discovery before versus after 6 weeks. Among the 458 women in the sample, 28% discovered their pregnancy later than 6 weeks since LMP. Most (n=366, 80%) knew the exact date of their LMP and a significant minority estimated it (n=92, 20%). Those who estimated the date of their LMP had higher odds of later pregnancy discovery than those who knew the exact date (adjusted odds ratio (aOR)=1.81[1.07-3.07]). Those who used illicit drugs weekly, daily, or almost daily had higher odds of later pregnancy discovery (aOR=6.33[2.44, 16.40]). Women who did not track their menstrual periods and those who frequently used drugs had higher odds of discovering their pregnancies later. Women who estimated the date of their LMP and who frequently used drugs may benefit from strategies to help them recognize their pregnancies earlier and link them to care when they discover their pregnancies later. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Pharmacological screening technologies for venom peptide discovery.

    Prashanth, Jutty Rajan; Hasaballah, Nojod; Vetter, Irina

    2017-12-01

    Venomous animals occupy one of the most successful evolutionary niches and occur on nearly every continent. They deliver venoms via biting and stinging apparatuses with the aim to rapidly incapacitate prey and deter predators. This has led to the evolution of venom components that act at a number of biological targets - including ion channels, G-protein coupled receptors, transporters and enzymes - with exquisite selectivity and potency, making venom-derived components attractive pharmacological tool compounds and drug leads. In recent years, plate-based pharmacological screening approaches have been introduced to accelerate venom-derived drug discovery. A range of assays are amenable to this purpose, including high-throughput electrophysiology, fluorescence-based functional and binding assays. However, despite these technological advances, the traditional activity-guided fractionation approach is time-consuming and resource-intensive. The combination of screening techniques suitable for miniaturization with sequence-based discovery approaches - supported by advanced proteomics, mass spectrometry, chromatography as well as synthesis and expression techniques - promises to further improve venom peptide discovery. Here, we discuss practical aspects of establishing a pipeline for venom peptide drug discovery with a particular emphasis on pharmacology and pharmacological screening approaches. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Shotgun Proteomics and Biomarker Discovery

    W. Hayes McDonald

    2002-01-01

    Full Text Available Coupling large-scale sequencing projects with the amino acid sequence information that can be gleaned from tandem mass spectrometry (MS/MS has made it much easier to analyze complex mixtures of proteins. The limits of this “shotgun” approach, in which the protein mixture is proteolytically digested before separation, can be further expanded by separating the resulting mixture of peptides prior to MS/MS analysis. Both single dimensional high pressure liquid chromatography (LC and multidimensional LC (LC/LC can be directly interfaced with the mass spectrometer to allow for automated collection of tremendous quantities of data. While there is no single technique that addresses all proteomic challenges, the shotgun approaches, especially LC/LC-MS/MS-based techniques such as MudPIT (multidimensional protein identification technology, show advantages over gel-based techniques in speed, sensitivity, scope of analysis, and dynamic range. Advances in the ability to quantitate differences between samples and to detect for an array of post-translational modifications allow for the discovery of classes of protein biomarkers that were previously unassailable.

  9. Link layer topology discovery in an uncooperative ethernet environment

    Delport, JP

    2007-05-01

    Full Text Available single destination is called a unicast address. Ethernet addresses also exist for sending data to multiple stations at once and are called multicast addresses. A special address, with all the bits in the address set to one (FF:FF:FF:FF:FF:FF), is used... P (2007) 2.4. Relevant Ethernet Concepts 14 Destination and source addresses are MAC addresses as defined in Sec- tion 2.4.2. The destination address might contain a unicast, multicast or broadcast address. The length or type field allows two types...

  10. Why should we publish Linked Data?

    Blower, Jon; Riechert, Maik; Koubarakis, Manolis; Pace, Nino

    2016-04-01

    publishing Linked Data will result in tangible user benefits. This presentation will address a number of these issues, using real-world experience gathered from four recent European projects: MELODIES (http://melodiesproject.eu), LEO (http://linkedeodata.eu), CHARMe (http://linkedeodata.eu) and TELEIOS (http://www.earthobservatory.eu). These projects have all applied Linked Data techniques in practical, real-world situations involving the use of diverse data (including earth science data) by both industrial and academic users. Specifically, we will: • Identify a set of practical and valuable uses for Linked Data, focusing on areas where Linked Data fills gaps left by other technologies. These uses include: enabling the discovery of earth science data using mass-market search engines, helping users to understand data and its uses, combining data from multiple sources and enabling the annotation of data by users. • Enumerate some common challenges faced by developers of data-driven services who wish to use Linked Data in their applications. • Describe a new suite of tools for managing, processing and visualising Linked Data in earth science applications (including geospatial Linked Data).

  11. Node Discovery and Interpretation in Unstructured Resource-Constrained Environments

    Gechev, Miroslav; Kasabova, Slavyana; Mihovska, Albena D.

    2014-01-01

    for the discovery, linking and interpretation of nodes in unstructured and resource-constrained network environments and their interrelated and collective use for the delivery of smart services. The model is based on a basic mathematical approach, which describes and predicts the success of human interactions...... in the context of long-term relationships and identifies several key variables in the context of communications in resource-constrained environments. The general theoretical model is described and several algorithms are proposed as part of the node discovery, identification, and linking processes in relation...

  12. The action characterization matrix: A link between HERA (Human Events Reference for ATHEANA) and ATHEANA (a technique for human error analysis)

    Hahn, H.A.

    1997-01-01

    The Technique for Human Error Analysis (ATHEANA) is a newly developed human reliability analysis (HRA) methodology that aims to facilitate better representation and integration of human performance into probabilistic risk assessment (PRA) modeling and quantification by analyzing risk-significant operating experience in the context of existing behavior science models. The fundamental premise of ATHEANA is that error-forcing contexts (EFCs), which refer to combinations of equipment/material conditions and performance shaping factors (PSFs), set up or create the conditions under which unsafe actions (UAs) can occur. ATHEANA is being developed in the context of nuclear power plant (NPP) PRAs, and much of the language used to describe the method and provide examples of its application are specific to that industry. Because ATHEANA relies heavily on the analysis of operational events that have already occurred as a mechanism for generating creative thinking about possible EFCs, a database, called the Human Events Reference for ATHEANA (HERA), has been developed to support the methodology. Los Alamos National Laboratory's (LANL) Human Factors Group has recently joined the ATHEANA project team; LANL is responsible for further developing the database structure and for analyzing additional exemplar operational events for entry into the database. The Action Characterization Matrix (ACM) is conceived as a bridge between the HERA database structure and ATHEANA. Specifically, the ACM allows each unsafe action or human failure event to be characterized according to its representation along each of six different dimensions: system status, initiator status, unsafe action mechanism, information processing stage, equipment/material conditions, and performance shaping factors. This report describes the development of the ACM and provides details on the structure and content of its dimensions

  13. The neutron discovery

    Six, J.

    1987-01-01

    The neutron: who had first the idea, who discovered it, who established its main properties. To these apparently simple questions, multiple answers exist. The progressive discovery of the neutron is a marvellous illustration of some characteristics of the scientific research, where the unforeseen may be combined with the expected. This discovery is replaced in the context of the 1930's scientific effervescence that succeeded the revolutionary introduction of quantum mechanics. This book describes the works of Bothe, the Joliot-Curie and Chadwick which led to the neutron in an unexpected way. A historical analysis allows to give a new interpretation on the hypothesis suggested by the Joliot-Curie. Some texts of these days will help the reader to revive this fascinating story [fr

  14. Atlas of Astronomical Discoveries

    Schilling, Govert

    2011-01-01

    Four hundred years ago in Middelburg, in the Netherlands, the telescope was invented. The invention unleashed a revolution in the exploration of the universe. Galileo Galilei discovered mountains on the Moon, spots on the Sun, and moons around Jupiter. Christiaan Huygens saw details on Mars and rings around Saturn. William Herschel discovered a new planet and mapped binary stars and nebulae. Other astronomers determined the distances to stars, unraveled the structure of the Milky Way, and discovered the expansion of the universe. And, as telescopes became bigger and more powerful, astronomers delved deeper into the mysteries of the cosmos. In his Atlas of Astronomical Discoveries, astronomy journalist Govert Schilling tells the story of 400 years of telescopic astronomy. He looks at the 100 most important discoveries since the invention of the telescope. In his direct and accessible style, the author takes his readers on an exciting journey encompassing the highlights of four centuries of astronomy. Spectacul...

  15. Viral pathogen discovery

    Chiu, Charles Y

    2015-01-01

    Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other biological products for microbial contamination, and discovering novel viruses associated with both acute and chronic illnesses. Downstream studies such as genome assembly, epidemiologic screening, and a culture system or animal model of infection are necessary to establish an association of a candidate pathogen with disease. PMID:23725672

  16. Fateful discovery almost forgotten

    Anon.

    1989-01-01

    The paper reviews the discovery of the fission of uranium, which took place fifty years ago. A description is given of the work of Meitner and Frisch in interpreting the Fermi data on the bombardment of uranium nuclei with neutrons, i.e. proposing fission. The historical events associated with the development and exploitation of uranium fission are described, including the Manhattan Project, Hiroshima and Nagasaki, Shippingport, and Chernobyl. (U.K.)

  17. Discovery as a process

    Loehle, C.

    1994-05-01

    The three great myths, which form a sort of triumvirate of misunderstanding, are the Eureka! myth, the hypothesis myth, and the measurement myth. These myths are prevalent among scientists as well as among observers of science. The Eureka! myth asserts that discovery occurs as a flash of insight, and as such is not subject to investigation. This leads to the perception that discovery or deriving a hypothesis is a moment or event rather than a process. Events are singular and not subject to description. The hypothesis myth asserts that proper science is motivated by testing hypotheses, and that if something is not experimentally testable then it is not scientific. This myth leads to absurd posturing by some workers conducting empirical descriptive studies, who dress up their study with a ``hypothesis`` to obtain funding or get it published. Methods papers are often rejected because they do not address a specific scientific problem. The fact is that many of the great breakthroughs in silence involve methods and not hypotheses or arise from largely descriptive studies. Those captured by this myth also try to block funding for those developing methods. The third myth is the measurement myth, which holds that determining what to measure is straightforward, so one doesn`t need a lot of introspection to do science. As one ecologist put it to me ``Don`t give me any of that philosophy junk, just let me out in the field. I know what to measure.`` These myths lead to difficulties for scientists who must face peer review to obtain funding and to get published. These myths also inhibit the study of science as a process. Finally, these myths inhibit creativity and suppress innovation. In this paper I first explore these myths in more detail and then propose a new model of discovery that opens the supposedly miraculous process of discovery to doser scrutiny.

  18. Application of alpha spectrometry to the discovery of new elements by heavy-ion-beam bombardment

    Nitschke, J.M.

    1983-05-01

    Starting with polonium in 1898, α-spectrometry has played a decisive role in the discovery of new, heavy elements. For even-even nuclei, α-spectra have proved simple to interpret and exhibit systematic trends that allow extrapolation to unknown isotopes. The early discovery of the natural α-decay series led to the very powerful method of genetically linking the decay of new elements to the well-established α-emission of daughter and granddaughter nuclei. This technique has been used for all recent discoveries of new elements including Z = 109. Up to mendelevium (Z = 101), thin samples suitable for α-spectrometry were prepared by chemical methods. With the advent of heavy-ion accelerators new sample preparation methods emerged. These were based on the large momentum transfer associated with heavy-ion reactions, which produced energetic target recoils that, when ejected from the target, could be thermalized in He gas. Subsequent electrical deposition or a He-jet technique yielded samples that were not only thin enough for α-spectroscopy, but also for α- and #betta#-recoil experiments. Many variations of these methods have been developed and are discussed. For the synthesis of element 106 an aerosol-based recoil transport technique was devised. In the most recent experiments, α-spectrometry has been coupled with the magnetic analysis of the recoils. The time from production to analysis of an isotope has thereby been reduced to 10 - 6 s; while it was 10 - 1 to 10 0 s for He-jets and 10 1 to 10 3 s for rapid chemical separations. Experiments are now in progress to synthesize super heavy elements (SHE) and to analyze them with these latest techniques. Again, α-spectrometry will play a major role since the expected signature for the decay of a SHE is a sequence of α-decays followed by spontaneous fission

  19. Linked Ocean Data

    Leadbetter, Adam; Arko, Robert; Chandler, Cynthia; Shepherd, Adam

    2014-05-01

    Data repositories. The benefits of this approach include: increased interoperability between the metadata created by projects; improved data discovery as users of SeaDataNet, R2R and BCO-DMO terms can find data using labels with which they are familiar both standard tools and newly developed custom tools may be used to explore the data; and using standards means the custom tools are easier to develop Linked Data is a concept which has been in existence for nearly a decade, and has a simple set of formal best practices associated with it. Linked Data is increasingly being seen as a driver of the next generation of "community science" activities. While many data providers in the oceanographic domain may be unaware of Linked Data, they may also be providing it at one of its lower levels. Here we have shown that it is possible to deliver the highest standard of Linked Oceanographic Data, and some of the benefits of the approach.

  20. Data mining-aided materials discovery and optimization

    Wencong Lu

    2017-09-01

    Full Text Available Recent developments in data mining-aided materials discovery and optimization are reviewed in this paper, and an introduction to the materials data mining (MDM process is provided using case studies. Both qualitative and quantitative methods in machine learning can be adopted in the MDM process to accomplish different tasks in materials discovery, design, and optimization. State-of-the-art techniques in data mining-aided materials discovery and optimization are demonstrated by reviewing the controllable synthesis of dendritic Co3O4 superstructures, materials design of layered double hydroxide, battery materials discovery, and thermoelectric materials design. The results of the case studies indicate that MDM is a powerful approach for use in materials discovery and innovation, and will play an important role in the development of the Materials Genome Initiative and Materials Informatics.

  1. Operative Links

    Wistoft, Karen; Højlund, Holger

    2012-01-01

    and have been the object of great expectations concerning the ability to incorporate health concerns into every welfare area through health promotion strategies. The paper draws on results and analyses of a collective research project funded by the Danish National Research Council and carried out...... links' that indicate cooperative levels which facilitate a creative and innovative effort in disease prevention and health promotion targeted at children and adolescents - across traditional professional boundaries. It is proposed that such links are supported by network structures, shared semantics...

  2. Discovery of Uniformly Expanding Universe

    Cahill R. T.

    2012-01-01

    Full Text Available Saul Perlmutter and the Brian Schmidt – Adam Riess teams reported that their Friedmann-model GR-based analysis of their supernovae magnitude-redshift data re- vealed a new phenomenon of “dark energy” which, it is claimed, forms 73% of the energy / matter density of the present-epoch universe, and which is linked to the further claim of an accelerating expansion of the universe. In 2011 Perlmutter, Schmidt and Riess received the Nobel Prize in Physics “for the discovery of the accelerating ex- pansion of the Universe through observations of distant supernovae”. Here it is shown that (i a generic model-independent analysis of this data reveals a uniformly expanding universe, (ii their analysis actually used Newtonian gravity, and finally (iii the data, as well as the CMB fluctuation data, does not require “dark energy” nor “dark matter”, but instead reveals the phenomenon of a dynamical space, which is absent from the Friedmann model.

  3. 14 CFR 406.143 - Discovery.

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Discovery. 406.143 Section 406.143... Transportation Adjudications § 406.143 Discovery. (a) Initiation of discovery. Any party may initiate discovery... after a complaint has been filed. (b) Methods of discovery. The following methods of discovery are...

  4. Rough – Granular Computing knowledge discovery models

    Mohammed M. Eissa

    2016-11-01

    Full Text Available Medical domain has become one of the most important areas of research in order to richness huge amounts of medical information about the symptoms of diseases and how to distinguish between them to diagnose it correctly. Knowledge discovery models play vital role in refinement and mining of medical indicators to help medical experts to settle treatment decisions. This paper introduces four hybrid Rough – Granular Computing knowledge discovery models based on Rough Sets Theory, Artificial Neural Networks, Genetic Algorithm and Rough Mereology Theory. A comparative analysis of various knowledge discovery models that use different knowledge discovery techniques for data pre-processing, reduction, and data mining supports medical experts to extract the main medical indicators, to reduce the misdiagnosis rates and to improve decision-making for medical diagnosis and treatment. The proposed models utilized two medical datasets: Coronary Heart Disease dataset and Hepatitis C Virus dataset. The main purpose of this paper was to explore and evaluate the proposed models based on Granular Computing methodology for knowledge extraction according to different evaluation criteria for classification of medical datasets. Another purpose is to make enhancement in the frame of KDD processes for supervised learning using Granular Computing methodology.

  5. Scandinavian links

    Matthiessen, Christian Wichmann; Knowles, Richard D.

    2014-01-01

    are impressive mega structures spanning international waterways. These waterways between the Baltic Sea and the North Sea have played major roles in history. The length of each of the crossings are around 20 km. The fixed links closes gaps between the Scandinavian and European motorway and rail networks...

  6. Gene Linked to Excess Male Hormones in Female Infertility Disorder

    ... April 15, 2014 Gene linked to excess male hormones in female infertility disorder Discovery by NIH-supported ... may lead to the overproduction of androgens — male hormones similar to testosterone — occurring in women with polycystic ...

  7. Solution NMR Spectroscopy in Target-Based Drug Discovery.

    Li, Yan; Kang, Congbao

    2017-08-23

    Solution NMR spectroscopy is a powerful tool to study protein structures and dynamics under physiological conditions. This technique is particularly useful in target-based drug discovery projects as it provides protein-ligand binding information in solution. Accumulated studies have shown that NMR will play more and more important roles in multiple steps of the drug discovery process. In a fragment-based drug discovery process, ligand-observed and protein-observed NMR spectroscopy can be applied to screen fragments with low binding affinities. The screened fragments can be further optimized into drug-like molecules. In combination with other biophysical techniques, NMR will guide structure-based drug discovery. In this review, we describe the possible roles of NMR spectroscopy in drug discovery. We also illustrate the challenges encountered in the drug discovery process. We include several examples demonstrating the roles of NMR in target-based drug discoveries such as hit identification, ranking ligand binding affinities, and mapping the ligand binding site. We also speculate the possible roles of NMR in target engagement based on recent processes in in-cell NMR spectroscopy.

  8. Causality discovery technology

    Chen, M.; Ertl, T.; Jirotka, M.; Trefethen, A.; Schmidt, A.; Coecke, B.; Bañares-Alcántara, R.

    2012-11-01

    Causality is the fabric of our dynamic world. We all make frequent attempts to reason causation relationships of everyday events (e.g., what was the cause of my headache, or what has upset Alice?). We attempt to manage causality all the time through planning and scheduling. The greatest scientific discoveries are usually about causality (e.g., Newton found the cause for an apple to fall, and Darwin discovered natural selection). Meanwhile, we continue to seek a comprehensive understanding about the causes of numerous complex phenomena, such as social divisions, economic crisis, global warming, home-grown terrorism, etc. Humans analyse and reason causality based on observation, experimentation and acquired a priori knowledge. Today's technologies enable us to make observations and carry out experiments in an unprecedented scale that has created data mountains everywhere. Whereas there are exciting opportunities to discover new causation relationships, there are also unparalleled challenges to benefit from such data mountains. In this article, we present a case for developing a new piece of ICT, called Causality Discovery Technology. We reason about the necessity, feasibility and potential impact of such a technology.

  9. Automated Supernova Discovery (Abstract)

    Post, R. S.

    2015-12-01

    (Abstract only) We are developing a system of robotic telescopes for automatic recognition of Supernovas as well as other transient events in collaboration with the Puckett Supernova Search Team. At the SAS2014 meeting, the discovery program, SNARE, was first described. Since then, it has been continuously improved to handle searches under a wide variety of atmospheric conditions. Currently, two telescopes are used to build a reference library while searching for PSN with a partial library. Since data is taken every night without clouds, we must deal with varying atmospheric and high background illumination from the moon. Software is configured to identify a PSN, reshoot for verification with options to change the run plan to acquire photometric or spectrographic data. The telescopes are 24-inch CDK24, with Alta U230 cameras, one in CA and one in NM. Images and run plans are sent between sites so the CA telescope can search while photometry is done in NM. Our goal is to find bright PSNs with magnitude 17.5 or less which is the limit of our planned spectroscopy. We present results from our first automated PSN discoveries and plans for PSN data acquisition.

  10. Comparison of immunofluorescence and enzyme-linked immunosorbent assay and immunoglobulin G avidity techniques for screening of anti: Toxoplasma antibodies among single serum sample pregnant women in Tabriz, Iran

    Mehrangiz Rajaii

    2015-01-01

    Full Text Available Background: Congenital toxoplasmosis is that pregnant women acquire the infection during gestation; diagnosis of the acute infection during pregnancy is a complex subject of maternal toxoplasmosis. Thus, the presence of immunoglobulin G (IgG and/or IgM Toxoplasma antibodies in a single serum sample drawn during gestation cannot be used to define whether the infection was recently acquired or chronic. Materials and Methods: At this cross-sectional descriptive study, sera of 391 pregnant women examined and compared. They were in an age range of 21-35 years, referred by gynecologists and infectious disease specialists, during March 2012-April 2013. They have referred, 215 (54.98%, 102 (26%, 74 (18.92% in the first, second and third trimesters of gestation, respectively. For each of them, a questionnaire was completed and serum samples were prepared in an equal condition, examined according to the procedures of indirect immunofluorescence (IIF, enzyme-linked immunosorbent assay (ELISA and IgG Avidity techniques. Results: We have found 111 (28.38% seronegative and 280 (71.61% seropositive cases by IIF and 124 (31.70% seronegative, 267 (68.28% seropositive cases by ELISA. The IgG avidity test confirmed 45 (69.23% and 7 (10.76% doubtful cases of IgM test in IIF and ELISA techniques. Conclusions: This study highlights how to manage pregnant women with toxoplasmosis, especially in a single serum sample condition.

  11. Discovery of SM Higgs Boson in ATLAS Experiment

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 3. Discovery of SM Higgs Boson in ATLAS Experiment. Prafulla Kumar Behera. General Article Volume 18 Issue 3 March 2013 pp 248-263. Fulltext. Click here to view fulltext PDF. Permanent link:

  12. Instruction, Repetition, Discovery: Restoring the Historical Educational Role of Practice

    Trninic, Dragan

    2018-01-01

    This conceptual paper considers what it would mean to take seriously Freudenthal's suggestion that mathematics should be taught like swimming. The general claim being made is that "direct instruction" and "discovery" are not opposite but complementary, linked by repetitive yet explorative practice. This claim is elaborated…

  13. User-guided discovery of declarative process models

    Maggi, F.M.; Mooij, A.J.; Aalst, van der W.M.P.; Chawla, N.; King, I.; Sperduti, A.

    2011-01-01

    Process mining techniques can be used to effectively discover process models from logs with example behaviour. Cross-correlating a discovered model with information in the log can be used to improve the underlying process. However, existing process discovery techniques have two important drawbacks.

  14. Computational methods in drug discovery

    Sumudu P. Leelananda; Steffen Lindert

    2016-01-01

    The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery project...

  15. Application of plug-plug technique to ACE experiments for discovery of peptides binding to a larger target protein: a model study of calmodulin-binding fragments selected from a digested mixture of reduced BSA.

    Saito, Kazuki; Nakato, Mamiko; Mizuguchi, Takaaki; Wada, Shinji; Uchimura, Hiromasa; Kataoka, Hiroshi; Yokoyama, Shigeyuki; Hirota, Hiroshi; Kiso, Yoshiaki

    2014-03-01

    To discover peptide ligands that bind to a target protein with a higher molecular mass, a concise screening methodology has been established, by applying a "plug-plug" technique to ACE experiments. Exploratory experiments using three mixed peptides, mastoparan-X, β-endorphin, and oxytocin, as candidates for calmodulin-binding ligands, revealed that the technique not only reduces the consumption of the protein sample, but also increases the flexibility of the experimental conditions, by allowing the use of MS detection in the ACE experiments. With the plug-plug technique, the ACE-MS screening methodology successfully selected calmodulin-binding peptides from a random library with diverse constituents, such as protease digests of BSA. Three peptides with Kd values between 8-147 μM for calmodulin were obtained from a Glu-C endoprotease digest of reduced BSA, although the digest showed more than 70 peaks in its ACE-MS electropherogram. The method established here will be quite useful for the screening of peptide ligands, which have only low affinities due to their flexible chain structures but could potentially provide primary information for designing inhibitors against the target protein. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Hippocampus discovery First steps

    Eliasz Engelhardt

    Full Text Available The first steps of the discovery, and the main discoverers, of the hippocampus are outlined. Arantius was the first to describe a structure he named "hippocampus" or "white silkworm". Despite numerous controversies and alternate designations, the term hippocampus has prevailed until this day as the most widely used term. Duvernoy provided an illustration of the hippocampus and surrounding structures, considered the first by most authors, which appeared more than one and a half century after Arantius' description. Some authors have identified other drawings and texts which they claim predate Duvernoy's depiction, in studies by Vesalius, Varolio, Willis, and Eustachio, albeit unconvincingly. Considering the definition of the hippocampal formation as comprising the hippocampus proper, dentate gyrus and subiculum, Arantius and Duvernoy apparently described the gross anatomy of this complex. The pioneering studies of Arantius and Duvernoy revealed a relatively small hidden formation that would become one of the most valued brain structures.

  17. Discovery Mondays: Zoom on materials

    2003-01-01

    Following the success of the first Discovery Monday, which had over 100 visitors, the series of evening events in Microcosm continues. On Monday 2nd June, discover the world of materials. Find out how CERN scientists examine, manufacture and study different materials, at different scales. Did you know for example that using electrons you can observe a hair at a scale equivalent to looking at a boat with the naked eye? Also, that using ultrasound, you can measure the thickness of an object that is completely inaccessible? Find out more about these techniques, and also the high-tech machining and soldering that is carried out in CERN's central workshop. Plus, see how engineers can detect tiny leaks through solder points - essential for maintaining the vacuum in the LHC. The evening is open to all, without reservation, suggested age 12 and above. Rendez-vous in Microcosm on Monday 2nd June From 19.30 - 21.00 Free entry For more information : http://www.cern.ch/microcosm Using a scanning microscope, the head o...

  18. Knowledge Discovery from Vibration Measurements

    Jun Deng

    2014-01-01

    Full Text Available The framework as well as the particular algorithms of pattern recognition process is widely adopted in structural health monitoring (SHM. However, as a part of the overall process of knowledge discovery from data bases (KDD, the results of pattern recognition are only changes and patterns of changes of data features. In this paper, based on the similarity between KDD and SHM and considering the particularity of SHM problems, a four-step framework of SHM is proposed which extends the final goal of SHM from detecting damages to extracting knowledge to facilitate decision making. The purposes and proper methods of each step of this framework are discussed. To demonstrate the proposed SHM framework, a specific SHM method which is composed by the second order structural parameter identification, statistical control chart analysis, and system reliability analysis is then presented. To examine the performance of this SHM method, real sensor data measured from a lab size steel bridge model structure are used. The developed four-step framework of SHM has the potential to clarify the process of SHM to facilitate the further development of SHM techniques.

  19. [Fortuitous discovery of gallbladder cancer].

    Chiche, L; Metairie, S

    2001-12-01

    The prognosis of gallbladder cancer is basically dependent on the histological stage at diagnosis. In practice, the discovery of a small cancer of the bladder, generally during cholecystectomy give the patient a better care for curative treatment. The advent of laparoscopy has increased the number of cholecstectomies and could increase the frequency of this situation but also raises the difficult problem of metastatic dissemination. In the literature the figures on parietal metastasis after laparoscopy have ranged from 125% to 19%. The median delay to diagnosis of recurrence is 6 months. The cause of this phenomenon (role of the pneumoperitoneum) remains poorly elucidated. Risk factors for the development of a metastasis on the trocar orifice are: rupture of the gallbladder perioperatively and extraction of the gallbladder without protection. It is important to keep in mind this exceptional but serious risk and apply rigorous operative technique. In case of suspected gallbladder we do not advocate laparoscopy. Surgery (hepatectomy, lymphodenectomy, possibly resection of the biliary tract) would be indicted for all stages except pTis and T1a, taking into consideration the localization of the tumor and the patient's general status. It is also classical to recommend resection of the trocar orifices after laparoscopic cholecystectomy. There is a dual challenge today for small-sized gallbladder cancer: improving treatment and avoiding poorer prognosis due to the specific problems raised by laparoscopy.

  20. Linking lab and field

    Cronje, P.B.

    1988-01-01

    The multitude of different supplements recommended for animals grazing natural pastures, which testifies to the need for a metabolic basis for supplementary feeding practices. The first approach to this problem was to simulate different feeding conditions in the laboratory, where the metabolic responses of body tissues to changes in the supply of purified nutrients could be studied using radioisotope techniques. The second step was to link these fundamental studies to field conditions. The results of these studies suggest that the efficiency of feed conversion and growth rates of ruminants grazing winter pastures in the highveld region of South Africa could be substantially improved by strategic supplementation with glucose precursors. Acetate clearance rate represents a valuable link in the process of applying information obtained from controlled laboratory experiments to field conditions. As this technique is inexpensive, quick and simple to carry out, it is ideally suited to application under field conditions where the use of isotopes is impractical. By providing a link with field conditions, it greatly extended the scope and practical application of isotope tracer techniques

  1. Pattern Discovery in Time-Ordered Data; TOPICAL

    CONRAD, GREGORY N.; BRITANIK, JOHN M.; DELAND, SHARON M.; JENKIN, CHRISTINA L.

    2002-01-01

    This report describes the results of a Laboratory-Directed Research and Development project on techniques for pattern discovery in discrete event time series data. In this project, we explored two different aspects of the pattern matching/discovery problem. The first aspect studied was the use of Dynamic Time Warping for pattern matching in continuous data. In essence, DTW is a technique for aligning time series along the time axis to optimize the similarity measure. The second aspect studied was techniques for discovering patterns in discrete event data. We developed a pattern discovery tool based on adaptations of the A-priori and GSP (Generalized Sequential Pattern mining) algorithms. We then used the tool on three different application areas-unattended monitoring system data from a storage magazine, computer network intrusion detection, and analysis of robot training data

  2. Materials Discovery | Materials Science | NREL

    Discovery Materials Discovery Images of red and yellow particles NREL's research in materials characterization of sample by incoming beam and measuring outgoing particles, with data being stored and analyzed Staff Scientist Dr. Zakutayev specializes in design of novel semiconductor materials for energy

  3. Service discovery using Bloom filters

    Goering, P.T.H.; Heijenk, Geert; Lelieveldt, B.P.F.; Haverkort, Boudewijn R.H.M.; de Laat, C.T.A.M.; Heijnsdijk, J.W.J.

    A protocol to perform service discovery in adhoc networks is introduced in this paper. Attenuated Bloom filters are used to distribute services to nodes in the neighborhood and thus enable local service discovery. The protocol has been implemented in a discrete event simulator to investigate the

  4. On the pulse of discovery

    2017-12-01

    What started 50 years ago as a `smudge' on paper has flourished into a fundamental field of astrophysics replete with unexpected applications and exciting discoveries. To celebrate the discovery of pulsars, we look at the past, present and future of pulsar astrophysics.

  5. 29 CFR 2700.56 - Discovery; general.

    2010-07-01

    ...(c) or 111 of the Act has been filed. 30 U.S.C. 815(c) and 821. (e) Completion of discovery... 29 Labor 9 2010-07-01 2010-07-01 false Discovery; general. 2700.56 Section 2700.56 Labor... Hearings § 2700.56 Discovery; general. (a) Discovery methods. Parties may obtain discovery by one or more...

  6. 19 CFR 207.109 - Discovery.

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Discovery. 207.109 Section 207.109 Customs Duties... and Committee Proceedings § 207.109 Discovery. (a) Discovery methods. All parties may obtain discovery under such terms and limitations as the administrative law judge may order. Discovery may be by one or...

  7. 30 CFR 44.24 - Discovery.

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Discovery. 44.24 Section 44.24 Mineral... Discovery. Parties shall be governed in their conduct of discovery by appropriate provisions of the Federal... discovery. Alternative periods of time for discovery may be prescribed by the presiding administrative law...

  8. 19 CFR 356.20 - Discovery.

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Discovery. 356.20 Section 356.20 Customs Duties... § 356.20 Discovery. (a) Voluntary discovery. All parties are encouraged to engage in voluntary discovery... sanctions proceeding. (b) Limitations on discovery. The administrative law judge shall place such limits...

  9. 24 CFR 180.500 - Discovery.

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 180.500 Section 180.500... OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a) In general. This subpart governs discovery in aid of administrative proceedings under this part. Discovery in...

  10. 15 CFR 25.21 - Discovery.

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Discovery. 25.21 Section 25.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery. (d...

  11. 39 CFR 963.14 - Discovery.

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Discovery. 963.14 Section 963.14 Postal Service... PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a... such discovery as he or she deems reasonable and necessary. Discovery may include one or more of the...

  12. 22 CFR 224.21 - Discovery.

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 224.21 Section 224.21 Foreign....21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of... parties, discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery...

  13. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery

    Nicholas Ekow Thomford

    2018-05-01

    Full Text Available The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of “active compound” has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of ‘organ-on chip’ and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug

  14. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery.

    Thomford, Nicholas Ekow; Senthebane, Dimakatso Alice; Rowe, Arielle; Munro, Daniella; Seele, Palesa; Maroyi, Alfred; Dzobo, Kevin

    2018-05-25

    The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of "active compound" has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of 'organ-on chip' and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug development. This review

  15. Bioinformatics and biomarker discovery "Omic" data analysis for personalized medicine

    Azuaje, Francisco

    2010-01-01

    This book is designed to introduce biologists, clinicians and computational researchers to fundamental data analysis principles, techniques and tools for supporting the discovery of biomarkers and the implementation of diagnostic/prognostic systems. The focus of the book is on how fundamental statistical and data mining approaches can support biomarker discovery and evaluation, emphasising applications based on different types of "omic" data. The book also discusses design factors, requirements and techniques for disease screening, diagnostic and prognostic applications. Readers are provided w

  16. 'The Lusiads', poem of discovery

    Natasha Furlan Felizi

    2016-07-01

    Full Text Available The article proposes reading Os Lusíadas as a discovery journey. Discovery here read as aletheia or “revelation”, as proposed by Sophia de Mello Brey­ner Andresen in 1980. Using Martin Heidegger’s notion of aletheia in the book Parmenides along with Jorge de Sena and Sophia de Mello Breyner Andresen reflections on Camões, I’ll seek to point out alternative readings for Os Lusíadas as a “discovery journey”.

  17. Students Excited by Stellar Discovery

    2011-02-01

    ," confessed Thompson. "I'm going to study astrophysics." Snider is pleased with the idea of contributing to scientific knowledge. "I hope that astronomers at Green Bank and around the world can learn something from the discovery," he said. Mabry is simply awed. "We've actually been able to experience something," she said. The PSC will continue through 2011. Teachers interested in participating in the program can learn more at this link, http://www.gb.nrao.edu/epo/psc.shtml.

  18. RAS - Screens & Assays - Drug Discovery

    The RAS Drug Discovery group aims to develop assays that will reveal aspects of RAS biology upon which cancer cells depend. Successful assay formats are made available for high-throughput screening programs to yield potentially effective drug compounds.

  19. Antibody informatics for drug discovery

    Shirai, Hiroki; Prades, Catherine; Vita, Randi

    2014-01-01

    to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic...... infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

  20. Discovery of the iron isotopes

    Schuh, A.; Fritsch, A.; Heim, M.; Shore, A.; Thoennessen, M.

    2010-01-01

    Twenty-eight iron isotopes have been observed so far and the discovery of these isotopes is discussed here. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  1. Discovery of the silver isotopes

    Schuh, A.; Fritsch, A.; Ginepro, J.Q.; Heim, M.; Shore, A.; Thoennessen, M.

    2010-01-01

    Thirty-eight silver isotopes have been observed so far and the discovery of these isotopes is discussed here. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  2. Synthetic biology of antimicrobial discovery

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

  3. Discovery of the cadmium isotopes

    Amos, S.; Thoennessen, M.

    2010-01-01

    Thirty-seven cadmium isotopes have been observed so far and the discovery of these isotopes is discussed here. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  4. Discoveries of isotopes by fission

    country of discovery as well as the production mechanism used to produce the isotopes. ... the disintegration products of bombarded uranium, as a consequence of a ..... advanced accelerator and newly developed separation and detection ...

  5. Synthetic biology of antimicrobial discovery.

    Zakeri, Bijan; Lu, Timothy K

    2013-07-19

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug-resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery.

  6. The discovery of 'heavy light'

    Anon.

    1983-01-01

    The history of the discoveries of fundamental quanta is described starting from Maxwell's theory of electromagnetism up to the development of a theory of weak interaction and the detection of the W and Z bosons. (HSI).

  7. Discovery – Development of Rituximab

    NCI funded the development of rituximab, one of the first monoclonal antibody cancer treatments. With the discovery of rituximab, more than 70 percent of patients diagnosed with non-hodgkin lymphoma now live five years past their initial diagnosis.

  8. Multi-dimensional discovery of biomarker and phenotype complexes

    Huang Kun

    2010-10-01

    Full Text Available Abstract Background Given the rapid growth of translational research and personalized healthcare paradigms, the ability to relate and reason upon networks of bio-molecular and phenotypic variables at various levels of granularity in order to diagnose, stage and plan treatments for disease states is highly desirable. Numerous techniques exist that can be used to develop networks of co-expressed or otherwise related genes and clinical features. Such techniques can also be used to create formalized knowledge collections based upon the information incumbent to ontologies and domain literature. However, reports of integrative approaches that bridge such networks to create systems-level models of disease or wellness are notably lacking in the contemporary literature. Results In response to the preceding gap in knowledge and practice, we report upon a prototypical series of experiments that utilize multi-modal approaches to network induction. These experiments are intended to elicit meaningful and significant biomarker-phenotype complexes spanning multiple levels of granularity. This work has been performed in the experimental context of a large-scale clinical and basic science data repository maintained by the National Cancer Institute (NCI funded Chronic Lymphocytic Leukemia Research Consortium. Conclusions Our results indicate that it is computationally tractable to link orthogonal networks of genes, clinical features, and conceptual knowledge to create multi-dimensional models of interrelated biomarkers and phenotypes. Further, our results indicate that such systems-level models contain interrelated bio-molecular and clinical markers capable of supporting hypothesis discovery and testing. Based on such findings, we propose a conceptual model intended to inform the cross-linkage of the results of such methods. This model has as its aim the identification of novel and knowledge-anchored biomarker-phenotype complexes.

  9. Radioactivity. Centenary of radioactivity discovery

    Charpak, G.; Tubiana, M.; Bimbot, R.

    1997-01-01

    This small booklet was edited for the occasion of the exhibitions of the celebration of the centenary of radioactivity discovery which took place in various locations in France from 1996 to 1998. It recalls some basic knowledge concerning radioactivity and its applications: history of discovery, atoms and isotopes, radiations, measurement of ionizing radiations, natural and artificial radioactivity, isotope dating and labelling, radiotherapy, nuclear power and reactors, fission and fusion, nuclear wastes, dosimetry, effects and radioprotection. (J.S.)

  10. Get Involved in Planetary Discoveries through New Worlds, New Discoveries

    Shupla, Christine; Shipp, S. S.; Halligan, E.; Dalton, H.; Boonstra, D.; Buxner, S.; SMD Planetary Forum, NASA

    2013-01-01

    "New Worlds, New Discoveries" is a synthesis of NASA’s 50-year exploration history which provides an integrated picture of our new understanding of our solar system. As NASA spacecraft head to and arrive at key locations in our solar system, "New Worlds, New Discoveries" provides an integrated picture of our new understanding of the solar system to educators and the general public! The site combines the amazing discoveries of past NASA planetary missions with the most recent findings of ongoing missions, and connects them to the related planetary science topics. "New Worlds, New Discoveries," which includes the "Year of the Solar System" and the ongoing celebration of the "50 Years of Exploration," includes 20 topics that share thematic solar system educational resources and activities, tied to the national science standards. This online site and ongoing event offers numerous opportunities for the science community - including researchers and education and public outreach professionals - to raise awareness, build excitement, and make connections with educators, students, and the public about planetary science. Visitors to the site will find valuable hands-on science activities, resources and educational materials, as well as the latest news, to engage audiences in planetary science topics and their related mission discoveries. The topics are tied to the big questions of planetary science: how did the Sun’s family of planets and bodies originate and how have they evolved? How did life begin and evolve on Earth, and has it evolved elsewhere in our solar system? Scientists and educators are encouraged to get involved either directly or by sharing "New Worlds, New Discoveries" and its resources with educators, by conducting presentations and events, sharing their resources and events to add to the site, and adding their own public events to the site’s event calendar! Visit to find quality resources and ideas. Connect with educators, students and the public to

  11. Optimizing Neighbor Discovery for Ad hoc Networks based on the Bluetooth PAN Profile

    Kuijpers, Gerben; Nielsen, Thomas Toftegaard; Prasad, Ramjee

    2002-01-01

    IP layer neighbor discovery mechanisms rely highly on broadcast/multicast capabilities of the underlying link layer. The Bluetooth personal area network (PAN) profile has no native link layer broadcast/multicast capabilities and can only emulate this by repeatedly unicast link layer frames....... This paper introduces a neighbor discovery mechanism that utilizes the resources in the Bluetooth PAN profile more efficient. The performance of the new mechanism is investigated using a IPv6 network simulator and compared with emulated broadcasting. It is shown that the signaling overhead can...

  12. X-Ray Astronomy Discovery Experiments, III*

    Fisher, P. C.

    2011-04-01

    The first paper established the existence of concurrent discovery experiments by Riccardo Giacconi and myself at the start of x-ray astronomy.footnotetextR. Giacconi et al., Phys. Rev. Lett. 9, 439 (1962).^,footnotetextP. C. Fisher et al., Quasars and High Energy Astronomy including Proceedings of the 2^nd Texas Symposium on Relativistic Astrophysics 15 - 19 December 1964 (K. N. Douglas et. al., eds.) Gordon and Breach Science Publishers, New York, p. 253 (1969).^,footnotetextP. C. Fisher, BAPS 53 No. 2, 165 (2008). Paper II footnotetextP.C. Fisher, http://www.aps.org/units/fhp/index.cfm plus FHP link to April 2009 presentation H14.00006. described some acts by some individuals/institutions over four decades that may have caused the illusion that I had not made a discovery. Some additional data about this illusion, and the first possible measurement of x-ray emission from a black hole, will be presented. This paper's primary goal is for the American Physical Society to have Giacconi comment on several questions of a historical nature. [4pt] *Work supported by NASA contracts NAS5-1174 and NASw-909, the Lockheed Independent Research Program, and Ruffner Associates.

  13. Business Model Discovery by Technology Entrepreneurs

    Steven Muegge

    2012-04-01

    Full Text Available Value creation and value capture are central to technology entrepreneurship. The ways in which a particular firm creates and captures value are the foundation of that firm's business model, which is an explanation of how the business delivers value to a set of customers at attractive profits. Despite the deep conceptual link between business models and technology entrepreneurship, little is known about the processes by which technology entrepreneurs produce successful business models. This article makes three contributions to partially address this knowledge gap. First, it argues that business model discovery by technology entrepreneurs can be, and often should be, disciplined by both intention and structure. Second, it provides a tool for disciplined business model discovery that includes an actionable process and a worksheet for describing a business model in a form that is both concise and explicit. Third, it shares preliminary results and lessons learned from six technology entrepreneurs applying a disciplined process to strengthen or reinvent the business models of their own nascent technology businesses.

  14. Discovery Mondays: crystals and particles for medicine

    2003-01-01

    Question: what are as heavy as lead, as clear as glass, and appear as tiny specks in a doctor's scanner but large as life in a physicist's detector? Answer: the crystals you will be able to observe in all their facets on 1 September at the start of a new season of Discovery Mondays at Microcosm. Come along and meet the CERN physicists who use crystals not only in their detectors but also in the latest generation of scanners. Four workshops will be organised, each devoted to a different medical imaging technique. The first workshop will be run by a physicist from the Crystal Clear collaboration, who will present her collaboration's special breed of crystals, which emit light when they are traversed by high-energy particles, and explain to you these crystals' role in Positron Emission Tomographs. The second workshop will focus on an imaging technique known as the Compton Camera, also based on scintillating crystals. Crystals worth looking at and admiring. Come to the next Discovery Monday to find out how they ...

  15. Feedback-Driven Dynamic Invariant Discovery

    Zhang, Lingming; Yang, Guowei; Rungta, Neha S.; Person, Suzette; Khurshid, Sarfraz

    2014-01-01

    Program invariants can help software developers identify program properties that must be preserved as the software evolves, however, formulating correct invariants can be challenging. In this work, we introduce iDiscovery, a technique which leverages symbolic execution to improve the quality of dynamically discovered invariants computed by Daikon. Candidate invariants generated by Daikon are synthesized into assertions and instrumented onto the program. The instrumented code is executed symbolically to generate new test cases that are fed back to Daikon to help further re ne the set of candidate invariants. This feedback loop is executed until a x-point is reached. To mitigate the cost of symbolic execution, we present optimizations to prune the symbolic state space and to reduce the complexity of the generated path conditions. We also leverage recent advances in constraint solution reuse techniques to avoid computing results for the same constraints across iterations. Experimental results show that iDiscovery converges to a set of higher quality invariants compared to the initial set of candidate invariants in a small number of iterations.

  16. Analyzing Student Inquiry Data Using Process Discovery and Sequence Classification

    Emond, Bruno; Buffett, Scott

    2015-01-01

    This paper reports on results of applying process discovery mining and sequence classification mining techniques to a data set of semi-structured learning activities. The main research objective is to advance educational data mining to model and support self-regulated learning in heterogeneous environments of learning content, activities, and…

  17. Genome engineering for microbial natural product discovery.

    Choi, Si-Sun; Katsuyama, Yohei; Bai, Linquan; Deng, Zixin; Ohnishi, Yasuo; Kim, Eung-Soo

    2018-03-03

    The discovery and development of microbial natural products (MNPs) have played pivotal roles in the fields of human medicine and its related biotechnology sectors over the past several decades. The post-genomic era has witnessed the development of microbial genome mining approaches to isolate previously unsuspected MNP biosynthetic gene clusters (BGCs) hidden in the genome, followed by various BGC awakening techniques to visualize compound production. Additional microbial genome engineering techniques have allowed higher MNP production titers, which could complement a traditional culture-based MNP chasing approach. Here, we describe recent developments in the MNP research paradigm, including microbial genome mining, NP BGC activation, and NP overproducing cell factory design. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Entity Linking Leveraging the GeoDeepDive Cyberinfrastructure and Managing Uncertainty with Provenance.

    Maio, R.; Arko, R. A.; Lehnert, K.; Ji, P.

    2017-12-01

    Unlocking the full, rich, network of links between the scientific literature and the real world entities to which data correspond - such as field expeditions (cruises) on oceanographic research vessels and physical samples collected during those expeditions - remains a challenge for the geoscience community. Doing so would enable data reuse and integration on a broad scale; making it possible to inspect the network and discover, for example, all rock samples reported in the scientific literature found within 10 kilometers of an undersea volcano, and associated geochemical analyses. Such a capability could facilitate new scientific discoveries. The GeoDeepDive project provides negotiated access to 4.2+ million documents from scientific publishers, enabling text and document mining via a public API and cyberinfrastructure. We mined this corpus using entity linking techniques, which are inherently uncertain, and recorded provenance information about each link. This opens the entity linking methodology to scrutiny, and enables downstream applications to make informed assessments about the suitability of an entity link for consumption. A major challenge is how to model and disseminate the provenance information. We present results from entity linking between journal articles, research vessels and cruises, and physical samples from the Petrological Database (PetDB), and incorporate Linked Data resources such as cruises in the Rolling Deck to Repository (R2R) catalog where possible. Our work demonstrates the value and potential of the GeoDeepDive cyberinfrastructure in combination with Linked Data infrastructure provided by the EarthCube GeoLink project. We present a research workflow to capture provenance information that leverages the World Wide Web Consortium (W3C) recommendation PROV Ontology.

  19. 42 CFR 426.432 - Discovery.

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Discovery. 426.432 Section 426.432 Public Health... § 426.432 Discovery. (a) General rule. If the ALJ orders discovery, the ALJ must establish a reasonable timeframe for discovery. (b) Protective order—(1) Request for a protective order. Any party receiving a...

  20. 40 CFR 27.21 - Discovery.

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Discovery. 27.21 Section 27.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the presiding officer. The presiding officer shall regulate the...

  1. 13 CFR 134.213 - Discovery.

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Discovery. 134.213 Section 134.213... OFFICE OF HEARINGS AND APPEALS Rules of Practice for Most Cases § 134.213 Discovery. (a) Motion. A party may obtain discovery only upon motion, and for good cause shown. (b) Forms. The forms of discovery...

  2. 37 CFR 41.150 - Discovery.

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Discovery. 41.150 Section 41... COMMERCE PRACTICE BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES Contested Cases § 41.150 Discovery. (a) Limited discovery. A party is not entitled to discovery except as authorized in this subpart. The...

  3. 19 CFR 354.10 - Discovery.

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Discovery. 354.10 Section 354.10 Customs Duties... ANTIDUMPING OR COUNTERVAILING DUTY ADMINISTRATIVE PROTECTIVE ORDER § 354.10 Discovery. (a) Voluntary discovery. All parties are encouraged to engage in voluntary discovery procedures regarding any matter, not...

  4. 14 CFR 13.220 - Discovery.

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Discovery. 13.220 Section 13.220... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Rules of Practice in FAA Civil Penalty Actions § 13.220 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or...

  5. 49 CFR 604.38 - Discovery.

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Discovery. 604.38 Section 604.38 Transportation... TRANSPORTATION CHARTER SERVICE Hearings. § 604.38 Discovery. (a) Permissible forms of discovery shall be within the discretion of the PO. (b) The PO shall limit the frequency and extent of discovery permitted by...

  6. 15 CFR 719.10 - Discovery.

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 719.10 Section 719.10... Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter... the Federal Rules of Civil Procedure relating to discovery apply to the extent consistent with this...

  7. 14 CFR 16.213 - Discovery.

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Discovery. 16.213 Section 16.213... PRACTICE FOR FEDERALLY-ASSISTED AIRPORT ENFORCEMENT PROCEEDINGS Hearings § 16.213 Discovery. (a) Discovery... discovery permitted by this section if a party shows that— (1) The information requested is cumulative or...

  8. 28 CFR 76.21 - Discovery.

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Discovery. 76.21 Section 76.21 Judicial... POSSESSION OF CERTAIN CONTROLLED SUBSTANCES § 76.21 Discovery. (a) Scope. Discovery under this part covers... as a general guide for discovery practices in proceedings before the Judge. However, unless otherwise...

  9. 36 CFR 1150.63 - Discovery.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Discovery. 1150.63 Section... PRACTICE AND PROCEDURES FOR COMPLIANCE HEARINGS Prehearing Conferences and Discovery § 1150.63 Discovery. (a) Parties are encouraged to engage in voluntary discovery procedures. For good cause shown under...

  10. 10 CFR 13.21 - Discovery.

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Discovery. 13.21 Section 13.21 Energy NUCLEAR REGULATORY COMMISSION PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) The following types of discovery are...) Unless mutually agreed to by the parties, discovery is available only as ordered by the ALJ. The ALJ...

  11. 49 CFR 1121.2 - Discovery.

    2010-10-01

    ... 49 Transportation 8 2010-10-01 2010-10-01 false Discovery. 1121.2 Section 1121.2 Transportation... TRANSPORTATION RULES OF PRACTICE RAIL EXEMPTION PROCEDURES § 1121.2 Discovery. Discovery shall follow the procedures set forth at 49 CFR part 1114, subpart B. Discovery may begin upon the filing of the petition for...

  12. 24 CFR 26.18 - Discovery.

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 26.18 Section 26.18... PROCEDURES Hearings Before Hearing Officers Discovery § 26.18 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery procedures, which may commence at any time after an answer has...

  13. 38 CFR 42.21 - Discovery.

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Discovery. 42.21 Section... IMPLEMENTING THE PROGRAM FRAUD CIVIL REMEDIES ACT § 42.21 Discovery. (a) The following types of discovery are... creation of a document. (c) Unless mutually agreed to by the parties, discovery is available only as...

  14. 22 CFR 521.21 - Discovery.

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Discovery. 521.21 Section 521.21 Foreign... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for... interpreted to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery is...

  15. 31 CFR 10.71 - Discovery.

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Discovery. 10.71 Section 10.71 Money... SERVICE Rules Applicable to Disciplinary Proceedings § 10.71 Discovery. (a) In general. Discovery may be... relevance, materiality and reasonableness of the requested discovery and subject to the requirements of § 10...

  16. 42 CFR 426.532 - Discovery.

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Discovery. 426.532 Section 426.532 Public Health... § 426.532 Discovery. (a) General rule. If the Board orders discovery, the Board must establish a reasonable timeframe for discovery. (b) Protective order—(1) Request for a protective order. Any party...

  17. 39 CFR 955.15 - Discovery.

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Discovery. 955.15 Section 955.15 Postal Service... APPEALS § 955.15 Discovery. (a) The parties are encouraged to engage in voluntary discovery procedures. In connection with any deposition or other discovery procedure, the Board may issue any order which justice...

  18. 49 CFR 1503.633 - Discovery.

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Discovery. 1503.633 Section 1503.633... Rules of Practice in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or approval of the ALJ, at...

  19. 43 CFR 35.21 - Discovery.

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discovery. 35.21 Section 35.21 Public... AND STATEMENTS § 35.21 Discovery. (a) The following types of discovery are authorized: (1) Requests...) Unless mutually agreed to by the parties, discovery is available only as ordered by the ALJ. The ALJ...

  20. 14 CFR 1264.120 - Discovery.

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Discovery. 1264.120 Section 1264.120... PENALTIES ACT OF 1986 § 1264.120 Discovery. (a) The following types of discovery are authorized: (1..., discovery is available only as ordered by the presiding officer. The presiding officer shall regulate the...

  1. 22 CFR 128.6 - Discovery.

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 128.6 Section 128.6 Foreign... Discovery. (a) Discovery by the respondent. The respondent, through the Administrative Law Judge, may... discovery if the interests of national security or foreign policy so require, or if necessary to comply with...

  2. 37 CFR 11.52 - Discovery.

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Discovery. 11.52 Section 11... Disciplinary Proceedings; Jurisdiction, Sanctions, Investigations, and Proceedings § 11.52 Discovery. Discovery... establishes that discovery is reasonable and relevant, the hearing officer, under such conditions as he or she...

  3. 24 CFR 26.42 - Discovery.

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 26.42 Section 26.42... PROCEDURES Hearings Pursuant to the Administrative Procedure Act Discovery § 26.42 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery procedures, which may commence at any time...

  4. 49 CFR 386.37 - Discovery.

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Discovery. 386.37 Section 386.37 Transportation... and Hearings § 386.37 Discovery. (a) Parties may obtain discovery by one or more of the following...; and requests for admission. (b) Discovery may not commence until the matter is pending before the...

  5. 29 CFR 1955.32 - Discovery.

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Discovery. 1955.32 Section 1955.32 Labor Regulations...) PROCEDURES FOR WITHDRAWAL OF APPROVAL OF STATE PLANS Preliminary Conference and Discovery § 1955.32 Discovery... allow discovery by any other appropriate procedure, such as by interrogatories upon a party or request...

  6. 31 CFR 16.21 - Discovery.

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Discovery. 16.21 Section 16.21 Money... FRAUD CIVIL REMEDIES ACT OF 1986 § 16.21 Discovery. (a) The following types of discovery are authorized... to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery is...

  7. 15 CFR 766.9 - Discovery.

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 766.9 Section 766.9... PROCEEDINGS § 766.9 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery... provisions of the Federal Rules of Civil Procedure relating to discovery apply to the extent consistent with...

  8. 43 CFR 4.1130 - Discovery methods.

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discovery methods. 4.1130 Section 4.1130... Special Rules Applicable to Surface Coal Mining Hearings and Appeals Discovery § 4.1130 Discovery methods. Parties may obtain discovery by one or more of the following methods— (a) Depositions upon oral...

  9. A novel approach to Service Discovery in Mobile Adhoc Network

    Islam, Noman; Shaikh, Zubair A.

    2015-01-01

    Mobile Adhoc Network (MANET) is a network of a number of mobile routers and associated hosts, organized in a random fashion via wireless links. During recent years MANET has gained enormous amount of attention and has been widely used for not only military purposes but for search-and-rescue operations, intelligent transportation system, data collection, virtual classrooms and ubiquitous computing. Service Discovery is one of the most important issues in MANET. It is defined as the process of ...

  10. Sex-linked dominant

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

  11. The Europa Ocean Discovery mission

    Edwards, B.C. [Los Alamos National Lab., NM (United States); Chyba, C.F. [Univ. of Arizona, Tucson, AZ (United States); Abshire, J.B. [National Aeronautics and Space Administration, Greenbelt, MD (United States). Goddard Space Flight Center] [and others

    1997-06-01

    Since it was first proposed that tidal heating of Europa by Jupiter might lead to liquid water oceans below Europa`s ice cover, there has been speculation over the possible exobiological implications of such an ocean. Liquid water is the essential ingredient for life as it is known, and the existence of a second water ocean in the Solar System would be of paramount importance for seeking the origin and existence of life beyond Earth. The authors present here a Discovery-class mission concept (Europa Ocean Discovery) to determine the existence of a liquid water ocean on Europa and to characterize Europa`s surface structure. The technical goal of the Europa Ocean Discovery mission is to study Europa with an orbiting spacecraft. This goal is challenging but entirely feasible within the Discovery envelope. There are four key challenges: entering Europan orbit, generating power, surviving long enough in the radiation environment to return valuable science, and complete the mission within the Discovery program`s launch vehicle and budget constraints. The authors will present here a viable mission that meets these challenges.

  12. Virtual Screening as a Technique for PPAR Modulator Discovery

    Stephanie N. Lewis

    2010-01-01

    agonists have therapeutic applications as insulin sensitizers in type 2 diabetes or as anti-inflammatories. VS is a cost- and time-effective means for identifying small molecules that have therapeutic potential. Our long-term goal is to devise computational approaches for testing the PPARγ-binding activity of extensive naturally occurring compound libraries prior to testing agonist activity using ligand-binding and reporter assays. This review summarizes the high potential for obtaining further fundamental understanding of PPARγ biology and development of novel therapies for treating chronic inflammatory diseases through evolution and implementation of computational screening processes for immunotherapeutics in conjunction with experimental methods for calibration and validation of results.

  13. Discovery of the Higgs boson

    Sharma, Vivek

    2016-01-01

    The recent observation of the Higgs boson has been hailed as the scientific discovery of the century and led to the 2013 Nobel Prize in physics. This book describes the detailed science behind the decades-long search for this elusive particle at the Large Electron Positron Collider at CERN and at the Tevatron at Fermilab and its subsequent discovery and characterization at the Large Hadron Collider at CERN. Written by physicists who played leading roles in this epic search and discovery, this book is an authoritative and pedagogical exposition of the portrait of the Higgs boson that has emerged from a large number of experimental measurements. As the first of its kind, this book should be of interest to graduate students and researchers in particle physics.

  14. Bioinformatics in translational drug discovery.

    Wooller, Sarah K; Benstead-Hume, Graeme; Chen, Xiangrong; Ali, Yusuf; Pearl, Frances M G

    2017-08-31

    Bioinformatics approaches are becoming ever more essential in translational drug discovery both in academia and within the pharmaceutical industry. Computational exploitation of the increasing volumes of data generated during all phases of drug discovery is enabling key challenges of the process to be addressed. Here, we highlight some of the areas in which bioinformatics resources and methods are being developed to support the drug discovery pipeline. These include the creation of large data warehouses, bioinformatics algorithms to analyse 'big data' that identify novel drug targets and/or biomarkers, programs to assess the tractability of targets, and prediction of repositioning opportunities that use licensed drugs to treat additional indications. © 2017 The Author(s).

  15. The discovery of subatomic particles

    Weinberg, S.

    1984-01-01

    This book developed from a course for students with no prior training in mathematics of physics to learn about the achievements of 20th century physics and classical physics. It covers the discovery of fundamental particles of ordinary atoms: the electron, the proton, and the neutron. The general outline is historical and it is for readers unfamiliar with classical physics who wish to understand the ideas and experiments that make up the history of 20th century physics. Contents include: A world of particles, the discovery of the electron, the atomic scale, the nucleus, more particles

  16. Advanced electron beam techniques

    Hirotsu, Yoshihiko; Yoshida, Yoichi

    2007-01-01

    After 100 years from the time of discovery of electron, we now have many applications of electron beam in science and technology. In this report, we review two important applications of electron beam: electron microscopy and pulsed-electron beam. Advanced electron microscopy techniques to investigate atomic and electronic structures, and pulsed-electron beam for investigating time-resolved structural change are described. (author)

  17. Anthelmintics: From discovery to resistance II (San Diego, 2016

    Richard J. Martin

    2016-12-01

    Full Text Available The second scientific meeting in the series: “Anthelmintics: From Discovery to Resistance” was held in San Diego in February, 2016. The focus topics of the meeting, related to anthelmintic discovery and resistance, were novel technologies, bioinformatics, commercial interests, anthelmintic modes of action and anthelmintic resistance. Basic scientific, human and veterinary interests were addressed in oral and poster presentations. The delegates were from universities and industries in the US, Europe, Australia and New Zealand. The papers were a great representation of the field, and included the use of C. elegans for lead discovery, mechanisms of anthelmintic resistance, nematode neuropeptides, proteases, B. thuringiensis crystal protein, nicotinic receptors, emodepside, benzimidazoles, P-glycoproteins, natural products, microfluidic techniques and bioinformatics approaches. The NIH also presented NIAID-specific parasite genomic priorities and initiatives. From these papers we introduce below selected papers with a focus on anthelmintic drug screening and development.

  18. Advances in fragment-based drug discovery platforms.

    Orita, Masaya; Warizaya, Masaichi; Amano, Yasushi; Ohno, Kazuki; Niimi, Tatsuya

    2009-11-01

    Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique. Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique. Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.

  19. Quarks, history of a discovery

    Husson, D.

    2000-01-01

    This book gives a presentation of quarks and stresses on the historical aspects of the studies that led to their discovery. The 'aesthetical' motivations of the scientists in their research are explained with only a minimum of mathematical concepts. (J.S.)

  20. On the threshold of discovery

    Cherenkov, P.A.

    1986-01-01

    The author, the discoverer of the Cherenkov radiation, recalls some interesting circumstances of his discoery 50 years ago and puts it into the context of the knowledge of the period. The discovery of Cherenkov radiation which today is in practice used especially for the detection of charged particles, was correctly understood and appreciated somewhat belatedly. At first the discovery was met with distrust and the original article announcing it was rejected by the magazine Nature. In effect, the discovery was not the result of any planned experiment but was the by-product of another research. It was, of course, allowed by previous achievements in various fields of physics, namely progress reached in the study of luminescence by S.I. Vavilov and his pupils. The discovery was made during an experimental study of luminescence induced in liquids by the β and γ radiations of uranyl salts. During his attempts to suppress the background radiation from vessel walls the autor found a ''background'' from pure solvent which differed from luminescence by being independent of the concentration, temperature and viscosity of the liquid. A closer examination of the phenomenon more or less by accident revealed its marked spatial asymmetry which had major importance for the development of the theory of the new phenomenon by I.V. Tamm and I.M. Frank. (A.K.)

  1. DISCOVERY IN THE URBAN SPRAWL.

    HYMOVITZ, LEON

    FOR A CULTURAL ENRICHMENT PROJECT ("DISCOVERY") IN A DISADVANTAGED PHILADELPIA HIGH SCHOOL, ATTENDANCE AT MUSIC, ART, AND THEATER EVENTS EARNED POINTS TOWARD A CERTIFICATE. THE STUDENTS ELECTED THE EVENTS FROM A PREPARED LIST OF ACTIVITIES, WHICH OFTEN WERE MADE PART OF THE ACADEMIC PROGRAM AND THE SCHOOL ASSEMBLIES. AS WELL AS OFFERING…

  2. Hubble 15 years of discovery

    Lindberg Christensen, Lars; Kornmesser, M

    2006-01-01

    Hubble: 15 Years of Discovery was a key element of the European Space Agency's 15th anniversary celebration activities for the 1990 launch of the NASA/ESA Hubble Space Telescope. As an observatory in space, Hubble is one of the most successful scientific projects of all time, both in terms of scientific output and its immediate public appeal.

  3. Nobel Prize Honors Autophagy Discovery.

    2016-12-01

    Japanese cell biologist Yoshinori Ohsumi, PhD, was awarded this year's Nobel Prize in Physiology or Medicine for his discovery of autophagy. His groundbreaking studies in yeast cells illuminated how cells break down and recycle damaged material, a process that is critical to the survival of both normal cells and some cancer cells. ©2016 American Association for Cancer Research.

  4. Translational medicine and drug discovery

    Littman, Bruce H; Krishna, Rajesh

    2011-01-01

    ..., and examples of their application to real-life drug discovery and development. The latest thinking is presented by researchers from many of the world's leading pharmaceutical companies, including Pfizer, Merck, Eli Lilly, Abbott, and Novartis, as well as from academic institutions and public- private partnerships that support translational research...

  5. New oil and gas discoveries

    Alazard-Toux, N.

    2004-01-01

    During the period 1999-2003, new oil and gas fields generated additional reserves of nearly 11 000 bcm of natural gas and 62 Gbbl of oil and condensates, volumes very much superior to those discovered in the five previous years. Two-thirds of these discoveries were located offshore, half in deep water. (author)

  6. Maximum Entropy in Drug Discovery

    Chih-Yuan Tseng

    2014-07-01

    Full Text Available Drug discovery applies multidisciplinary approaches either experimentally, computationally or both ways to identify lead compounds to treat various diseases. While conventional approaches have yielded many US Food and Drug Administration (FDA-approved drugs, researchers continue investigating and designing better approaches to increase the success rate in the discovery process. In this article, we provide an overview of the current strategies and point out where and how the method of maximum entropy has been introduced in this area. The maximum entropy principle has its root in thermodynamics, yet since Jaynes’ pioneering work in the 1950s, the maximum entropy principle has not only been used as a physics law, but also as a reasoning tool that allows us to process information in hand with the least bias. Its applicability in various disciplines has been abundantly demonstrated. We give several examples of applications of maximum entropy in different stages of drug discovery. Finally, we discuss a promising new direction in drug discovery that is likely to hinge on the ways of utilizing maximum entropy.

  7. Structural Biology Guides Antibiotic Discovery

    Polyak, Steven

    2014-01-01

    Modern drug discovery programs require the contribution of researchers in a number of specialist areas. One of these areas is structural biology. Using X-ray crystallography, the molecular basis of how a drug binds to its biological target and exerts its mode of action can be defined. For example, a drug that binds into the active site of an…

  8. Recent advances in inkjet dispensing technologies: applications in drug discovery.

    Zhu, Xiangcheng; Zheng, Qiang; Yang, Hu; Cai, Jin; Huang, Lei; Duan, Yanwen; Xu, Zhinan; Cen, Peilin

    2012-09-01

    Inkjet dispensing technology is a promising fabrication methodology widely applied in drug discovery. The automated programmable characteristics and high-throughput efficiency makes this approach potentially very useful in miniaturizing the design patterns for assays and drug screening. Various custom-made inkjet dispensing systems as well as specialized bio-ink and substrates have been developed and applied to fulfill the increasing demands of basic drug discovery studies. The incorporation of other modern technologies has further exploited the potential of inkjet dispensing technology in drug discovery and development. This paper reviews and discusses the recent developments and practical applications of inkjet dispensing technology in several areas of drug discovery and development including fundamental assays of cells and proteins, microarrays, biosensors, tissue engineering, basic biological and pharmaceutical studies. Progression in a number of areas of research including biomaterials, inkjet mechanical systems and modern analytical techniques as well as the exploration and accumulation of profound biological knowledge has enabled different inkjet dispensing technologies to be developed and adapted for high-throughput pattern fabrication and miniaturization. This in turn presents a great opportunity to propel inkjet dispensing technology into drug discovery.

  9. Managing Your Team's Weakest Link.

    Hills, Laura

    2015-01-01

    Do you have a poor-performing employee on your medical practice team? If so, you're not alone. Unfortunately, this is a problem that many medical practice managers face. This article describes the best strategies for managing your team's weakest link. It explores common yet very difficult circumstances that cause low employee performance and that test the patience, heart, and skills of a practice manager. It guides readers through a process of self-discovery to determine whether their negative biases or grudges may be causing employees to perform poorly. It suggests several possible other reasons for weak employee performance, including problems with the job, practice, leadership, communication, and fit between the employee and the job. This article also suggests the best strategy for communicating concerns about performance to the weakest-link employee. It offers guidance to practice managers about protecting their time and energy when handling a poor performer. It provides a simple formula for calculating the cost of a low-performing employee, 10 possible personal reasons for the employee's poor work performance, specific questions to ask to uncover the reasons for poor performance, and an eight-rule strategy for confronting poor performance effectively. Finally, this article offers practice managers a practical strategy for handling resistance from their weakest link, illustrated with a sample dialogue.

  10. Knowledge-Based Topic Model for Unsupervised Object Discovery and Localization.

    Niu, Zhenxing; Hua, Gang; Wang, Le; Gao, Xinbo

    Unsupervised object discovery and localization is to discover some dominant object classes and localize all of object instances from a given image collection without any supervision. Previous work has attempted to tackle this problem with vanilla topic models, such as latent Dirichlet allocation (LDA). However, in those methods no prior knowledge for the given image collection is exploited to facilitate object discovery. On the other hand, the topic models used in those methods suffer from the topic coherence issue-some inferred topics do not have clear meaning, which limits the final performance of object discovery. In this paper, prior knowledge in terms of the so-called must-links are exploited from Web images on the Internet. Furthermore, a novel knowledge-based topic model, called LDA with mixture of Dirichlet trees, is proposed to incorporate the must-links into topic modeling for object discovery. In particular, to better deal with the polysemy phenomenon of visual words, the must-link is re-defined as that one must-link only constrains one or some topic(s) instead of all topics, which leads to significantly improved topic coherence. Moreover, the must-links are built and grouped with respect to specific object classes, thus the must-links in our approach are semantic-specific , which allows to more efficiently exploit discriminative prior knowledge from Web images. Extensive experiments validated the efficiency of our proposed approach on several data sets. It is shown that our method significantly improves topic coherence and outperforms the unsupervised methods for object discovery and localization. In addition, compared with discriminative methods, the naturally existing object classes in the given image collection can be subtly discovered, which makes our approach well suited for realistic applications of unsupervised object discovery.Unsupervised object discovery and localization is to discover some dominant object classes and localize all of object

  11. Discovery Monday: How to measure success

    2003-01-01

    The last Discovery Monday which was carried out by the surveyors at CERN was a great success, one which they could not measure with their usual precision. The various entertaining as well as instructive experiments deserve a big "Thank you" to the SU group at the EST division. Children learn how to measure with the water level, like in Roman times.At CERN, photogrammetric techniques are used to precisely measure positions of complex ensembles like detectors. In Microcosm, photogrammetry is also invaluable to take the measure of visitors who can no longer cheat about their size. They were measured to a precision of one tenth of a millimetre and received a certificate.The alignment of accelerators is one of the big challenges for the surveyors at CERN. But even with good instruments, you need to have good eyes!

  12. Discovery Mondays - 'Eureka! Meet the inventors'

    2006-01-01

    Fabio Sauli, the inventor of the GEM detector. Do you imagine an invention as a spontaneous brainchild emergi from the convoluted mind of some scatterbrained and dishevelled scientist? If so, you are mistaken! Join us at Microcosm for the next Discovery Monday at which inventors will be the guests of honour. There you will meet scientists who, thanks to their creativity, have made technological progress possible. By constantly rising to new scientific and technological challenges, CERN has delivered numerous innovations, particularly in the medical field. Members of the Crystal Clear collaboration and the inventor of the GEM detector will give talks about their innovations and their applications, in particular for medical purposes. You will also be able to speak to members of the Medipix collaboration, which is working on improvements to X-ray and gamma ray imaging techniques. The event will be conducted in French. Come to Microcosm, (Reception Building 33, Meyrin site), on Monday 6 February from 7.30 p...

  13. A metadata initiative for global information discovery

    Christian, E.

    2001-01-01

    The Global Information Locator Service (GILS) encompasses a global vision framed by the fundamental values of open societies. Societal values such as a free flow of information impose certain requirements on the society's information infrastructure. These requirements in turn shape the various laws, policies, standards, and technologies that determine the infrastructure design. A particular focus of GILS is the requirement to provide the means for people to discover sources of data and information. Information discovery in the GILS vision is designed to be decentralized yet coherent, and globally comprehensive yet useful for detailed data. This article introduces basic concepts and design issues, with emphasis on the techniques by which GILS supports interoperability. It explains the practical implications of GILS for the common roles of organizations involved in handling information, from content provider through system engineer and intermediary to searcher. The article provides examples of GILS initiatives in various types of communities: bibliographic, geographic, environmental, and government. ?? 2001 Elsevier Science Inc.

  14. Perspectives on bioanalytical mass spectrometry and automation in drug discovery.

    Janiszewski, John S; Liston, Theodore E; Cole, Mark J

    2008-11-01

    The use of high speed synthesis technologies has resulted in a steady increase in the number of new chemical entities active in the drug discovery research stream. Large organizations can have thousands of chemical entities in various stages of testing and evaluation across numerous projects on a weekly basis. Qualitative and quantitative measurements made using LC/MS are integrated throughout this process from early stage lead generation through candidate nomination. Nearly all analytical processes and procedures in modern research organizations are automated to some degree. This includes both hardware and software automation. In this review we discuss bioanalytical mass spectrometry and automation as components of the analytical chemistry infrastructure in pharma. Analytical chemists are presented as members of distinct groups with similar skillsets that build automated systems, manage test compounds, assays and reagents, and deliver data to project teams. The ADME-screening process in drug discovery is used as a model to highlight the relationships between analytical tasks in drug discovery. Emerging software and process automation tools are described that can potentially address gaps and link analytical chemistry related tasks. The role of analytical chemists and groups in modern 'industrialized' drug discovery is also discussed.

  15. Quantifying the Ease of Scientific Discovery.

    Arbesman, Samuel

    2011-02-01

    It has long been known that scientific output proceeds on an exponential increase, or more properly, a logistic growth curve. The interplay between effort and discovery is clear, and the nature of the functional form has been thought to be due to many changes in the scientific process over time. Here I show a quantitative method for examining the ease of scientific progress, another necessary component in understanding scientific discovery. Using examples from three different scientific disciplines - mammalian species, chemical elements, and minor planets - I find the ease of discovery to conform to an exponential decay. In addition, I show how the pace of scientific discovery can be best understood as the outcome of both scientific output and ease of discovery. A quantitative study of the ease of scientific discovery in the aggregate, such as done here, has the potential to provide a great deal of insight into both the nature of future discoveries and the technical processes behind discoveries in science.

  16. Arthritis Genetics Analysis Aids Drug Discovery

    ... NIH Research Matters January 13, 2014 Arthritis Genetics Analysis Aids Drug Discovery An international research team identified 42 new ... Edition Distracted Driving Raises Crash Risk Arthritis Genetics Analysis Aids Drug Discovery Oxytocin Affects Facial Recognition Connect with Us ...

  17. Bioinformatics for cancer immunotherapy target discovery

    Olsen, Lars Rønn; Campos, Benito; Barnkob, Mike Stein

    2014-01-01

    therapy target discovery in a bioinformatics analysis pipeline. We describe specialized bioinformatics tools and databases for three main bottlenecks in immunotherapy target discovery: the cataloging of potentially antigenic proteins, the identification of potential HLA binders, and the selection epitopes...

  18. Cross-Layer Service Discovery Mechanism for OLSRv2 Mobile Ad Hoc Networks

    M. Isabel Vara

    2015-07-01

    Full Text Available Service discovery plays an important role in mobile ad hoc networks (MANETs. The lack of central infrastructure, limited resources and high mobility make service discovery a challenging issue for this kind of network. This article proposes a new service discovery mechanism for discovering and advertising services integrated into the Optimized Link State Routing Protocol Version 2 (OLSRv2. In previous studies, we demonstrated the validity of a similar service discovery mechanism integrated into the previous version of OLSR (OLSRv1. In order to advertise services, we have added a new type-length-value structure (TLV to the OLSRv2 protocol, called service discovery message (SDM, according to the Generalized MANET Packet/Message Format defined in Request For Comments (RFC 5444. Each node in the ad hoc network only advertises its own services. The advertisement frequency is a user-configurable parameter, so that it can be modified depending on the user requirements. Each node maintains two service tables, one to store information about its own services and another one to store information about the services it discovers in the network. We present simulation results, that compare our service discovery integrated into OLSRv2 with the one defined for OLSRv1 and with the integration of service discovery in Ad hoc On-demand Distance Vector (AODV protocol, in terms of service discovery ratio, service latency and network overhead.

  19. Cross-Layer Service Discovery Mechanism for OLSRv2 Mobile Ad Hoc Networks.

    Vara, M Isabel; Campo, Celeste

    2015-07-20

    Service discovery plays an important role in mobile ad hoc networks (MANETs). The lack of central infrastructure, limited resources and high mobility make service discovery a challenging issue for this kind of network. This article proposes a new service discovery mechanism for discovering and advertising services integrated into the Optimized Link State Routing Protocol Version 2 (OLSRv2). In previous studies, we demonstrated the validity of a similar service discovery mechanism integrated into the previous version of OLSR (OLSRv1). In order to advertise services, we have added a new type-length-value structure (TLV) to the OLSRv2 protocol, called service discovery message (SDM), according to the Generalized MANET Packet/Message Format defined in Request For Comments (RFC) 5444. Each node in the ad hoc network only advertises its own services. The advertisement frequency is a user-configurable parameter, so that it can be modified depending on the user requirements. Each node maintains two service tables, one to store information about its own services and another one to store information about the services it discovers in the network. We present simulation results, that compare our service discovery integrated into OLSRv2 with the one defined for OLSRv1 and with the integration of service discovery in Ad hoc On-demand Distance Vector (AODV) protocol, in terms of service discovery ratio, service latency and network overhead.

  20. Mass spectrometry-driven drug discovery for development of herbal medicine.

    Zhang, Aihua; Sun, Hui; Wang, Xijun

    2018-05-01

    Herbal medicine (HM) has made a major contribution to the drug discovery process with regard to identifying products compounds. Currently, more attention has been focused on drug discovery from natural compounds of HM. Despite the rapid advancement of modern analytical techniques, drug discovery is still a difficult and lengthy process. Fortunately, mass spectrometry (MS) can provide us with useful structural information for drug discovery, has been recognized as a sensitive, rapid, and high-throughput technology for advancing drug discovery from HM in the post-genomic era. It is essential to develop an efficient, high-quality, high-throughput screening method integrated with an MS platform for early screening of candidate drug molecules from natural products. We have developed a new chinmedomics strategy reliant on MS that is capable of capturing the candidate molecules, facilitating their identification of novel chemical structures in the early phase; chinmedomics-guided natural product discovery based on MS may provide an effective tool that addresses challenges in early screening of effective constituents of herbs against disease. This critical review covers the use of MS with related techniques and methodologies for natural product discovery, biomarker identification, and determination of mechanisms of action. It also highlights high-throughput chinmedomics screening methods suitable for lead compound discovery illustrated by recent successes. © 2016 Wiley Periodicals, Inc.

  1. The circumstances of minor planet discovery

    Pilcher, F.

    1989-01-01

    The circumstances of discoveries of minor planets are presented in tabular form. Complete data are given for planets 2125-4044, together with notes pertaining to these planets. Information in the table includes the permanent number; the official name; for planets 330 and forward, the table includes the provisional designation attached to the discovery apparition and the year, month, the day of discovery, and the discovery place

  2. 15 CFR 280.210 - Discovery.

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Discovery. 280.210 Section 280.210... STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE ACCREDITATION AND ASSESSMENT PROGRAMS FASTENER QUALITY Enforcement § 280.210 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery...

  3. 6 CFR 13.21 - Discovery.

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Discovery. 13.21 Section 13.21 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) In general. (1) The following types of discovery are authorized: (i) Requests for production of...

  4. 42 CFR 1005.7 - Discovery.

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Discovery. 1005.7 Section 1005.7 Public Health... OF EXCLUSIONS, CIVIL MONEY PENALTIES AND ASSESSMENTS § 1005.7 Discovery. (a) A party may make a... and any forms of discovery, other than those permitted under paragraph (a) of this section, are not...

  5. 42 CFR 405.1037 - Discovery.

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Discovery. 405.1037 Section 405.1037 Public Health... Appeals Under Original Medicare (Part A and Part B) Alj Hearings § 405.1037 Discovery. (a) General rules. (1) Discovery is permissible only when CMS or its contractor elects to participate in an ALJ hearing...

  6. 45 CFR 99.23 - Discovery.

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 99.23 Section 99.23 Public Welfare... DEVELOPMENT FUND Hearing Procedures § 99.23 Discovery. The Department, the Lead Agency, and any individuals or groups recognized as parties shall have the right to conduct discovery (including depositions) against...

  7. 29 CFR 1603.210 - Discovery.

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Discovery. 1603.210 Section 1603.210 Labor Regulations... GOVERNMENT EMPLOYEE RIGHTS ACT OF 1991 Hearings § 1603.210 Discovery. (a) Unless otherwise ordered by the administrative law judge, discovery may begin as soon as the complaint has been transmitted to the administrative...

  8. 41 CFR 60-30.33 - Discovery.

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Discovery. 60-30.33... 11246 Expedited Hearing Procedures § 60-30.33 Discovery. (a) Any party may serve requests for admissions... with § 60-30.8, the Administrative Law Judge may allow the taking of depositions. Other discovery will...

  9. 45 CFR 150.435 - Discovery.

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 150.435 Section 150.435 Public Welfare... AND INDIVIDUAL INSURANCE MARKETS Administrative Hearings § 150.435 Discovery. (a) The parties must identify any need for discovery from the opposing party as soon as possible, but no later than the time for...

  10. 10 CFR 1013.21 - Discovery.

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Discovery. 1013.21 Section 1013.21 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) PROGRAM FRAUD CIVIL REMEDIES AND PROCEDURES § 1013.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and...

  11. 20 CFR 355.21 - Discovery.

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Discovery. 355.21 Section 355.21 Employees... UNDER THE PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 355.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...

  12. 34 CFR 81.16 - Discovery.

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Discovery. 81.16 Section 81.16 Education Office of the... Discovery. (a) The parties to a case are encouraged to exchange relevant documents and information voluntarily. (b) The ALJ, at a party's request, may order compulsory discovery described in paragraph (c) of...

  13. 10 CFR 2.1018 - Discovery.

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Discovery. 2.1018 Section 2.1018 Energy NUCLEAR REGULATORY... Geologic Repository § 2.1018 Discovery. (a)(1) Parties, potential parties, and interested governmental participants in the high-level waste licensing proceeding may obtain discovery by one or more of the following...

  14. 45 CFR 213.23a - Discovery.

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Discovery. 213.23a Section 213.23a Public Welfare... Discovery. The Department and any party named in the notice issued pursuant to § 213.11 shall have the right to conduct discovery (including depositions) against opposing parties. Rules 26-37 of the Federal...

  15. 29 CFR 2200.208 - Discovery.

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Discovery. 2200.208 Section 2200.208 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION RULES OF PROCEDURE Simplified Proceedings § 2200.208 Discovery. Discovery, including requests for admissions, will only be...

  16. 47 CFR 65.105 - Discovery.

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Discovery. 65.105 Section 65.105... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Procedures § 65.105 Discovery. (a) Participants... evidence. (c) Discovery requests pursuant to § 65.105(b), including written interrogatories, shall be filed...

  17. 28 CFR 71.21 - Discovery.

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Discovery. 71.21 Section 71.21 Judicial... REMEDIES ACT OF 1986 Implementation for Actions Initiated by the Department of Justice § 71.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

  18. 13 CFR 134.310 - Discovery.

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Discovery. 134.310 Section 134.310 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION RULES OF PROCEDURE GOVERNING CASES BEFORE THE... Designations § 134.310 Discovery. Discovery will not be permitted in appeals from size determinations or NAICS...

  19. 20 CFR 498.207 - Discovery.

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Discovery. 498.207 Section 498.207 Employees... § 498.207 Discovery. (a) For the purpose of inspection and copying, a party may make a request to...) Any form of discovery other than that permitted under paragraph (a) of this section, such as requests...

  20. 29 CFR 1905.25 - Discovery.

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Discovery. 1905.25 Section 1905.25 Labor Regulations... OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 Hearings § 1905.25 Discovery. (a) Depositions. (1) For reasons of... discovery. Whenever appropriate to a just disposition of any issue in a hearing, the presiding hearing...

  1. 34 CFR 33.21 - Discovery.

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Discovery. 33.21 Section 33.21 Education Office of the Secretary, Department of Education PROGRAM FRAUD CIVIL REMEDIES ACT § 33.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying...

  2. 42 CFR 93.512 - Discovery.

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Discovery. 93.512 Section 93.512 Public Health... Process § 93.512 Discovery. (a) Request to provide documents. A party may only request another party to...) Responses to a discovery request. Within 30 days of receiving a request for the production of documents, a...

  3. 49 CFR 209.313 - Discovery.

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Discovery. 209.313 Section 209.313 Transportation... TRANSPORTATION RAILROAD SAFETY ENFORCEMENT PROCEDURES Disqualification Procedures § 209.313 Discovery. (a... parties. Discovery is designed to enable a party to obtain relevant information needed for preparation of...

  4. 12 CFR 1780.26 - Discovery.

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Discovery. 1780.26 Section 1780.26 Banks and... OF PRACTICE AND PROCEDURE RULES OF PRACTICE AND PROCEDURE Prehearing Proceedings § 1780.26 Discovery. (a) Limits on discovery. Subject to the limitations set out in paragraphs (b), (d), and (e) of this...

  5. 37 CFR 2.120 - Discovery.

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Discovery. 2.120 Section 2... COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Procedure in Inter Partes Proceedings § 2.120 Discovery. (a... to disclosure and discovery shall apply in opposition, cancellation, interference and concurrent use...

  6. 45 CFR 160.516 - Discovery.

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 160.516 Section 160.516 Public Welfare... ADMINISTRATIVE REQUIREMENTS Procedures for Hearings § 160.516 Discovery. (a) A party may make a request to... forms of discovery, other than those permitted under paragraph (a) of this section, are not authorized...

  7. 46 CFR 550.502 - Discovery.

    2010-10-01

    ... 46 Shipping 9 2010-10-01 2010-10-01 false Discovery. 550.502 Section 550.502 Shipping FEDERAL... Proceedings § 550.502 Discovery. The Commission may authorize a party to a proceeding to use depositions, written interrogatories, and discovery procedures that, to the extent practicable, are in conformity with...

  8. 28 CFR 18.7 - Discovery.

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Discovery. 18.7 Section 18.7 Judicial Administration DEPARTMENT OF JUSTICE OFFICE OF JUSTICE PROGRAMS HEARING AND APPEAL PROCEDURES § 18.7 Discovery.... Such order may be entered upon a showing that the deposition is necessary for discovery purposes, and...

  9. 10 CFR 205.198 - Discovery.

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Discovery. 205.198 Section 205.198 Energy DEPARTMENT OF... of Proposed Disallowance, and Order of Disallowance § 205.198 Discovery. (a) If a person intends to file a Motion for Discovery, he must file it at the same time that he files his Statement of Objections...

  10. 42 CFR 3.516 - Discovery.

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Discovery. 3.516 Section 3.516 Public Health PUBLIC... AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.516 Discovery. (a) A party may make a request... and any forms of discovery, other than those permitted under paragraph (a) of this section, are not...

  11. 12 CFR 908.46 - Discovery.

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Discovery. 908.46 Section 908.46 Banks and... PRACTICE AND PROCEDURE IN HEARINGS ON THE RECORD Pre-Hearing Proceedings § 908.46 Discovery. (a) Limits on discovery. Subject to the limitations set out in paragraphs (b), (d), and (e) of this section, any party to...

  12. 15 CFR 785.8 - Discovery.

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 785.8 Section 785.8... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS ENFORCEMENT § 785.8 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter, not...

  13. 22 CFR 35.21 - Discovery.

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 35.21 Section 35.21 Foreign Relations DEPARTMENT OF STATE CLAIMS AND STOLEN PROPERTY PROGRAM FRAUD CIVIL REMEDIES § 35.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

  14. 29 CFR 22.21 - Discovery.

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Discovery. 22.21 Section 22.21 Labor Office of the Secretary of Labor PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 22.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...

  15. 42 CFR 430.86 - Discovery.

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Discovery. 430.86 Section 430.86 Public Health... Plans and Practice to Federal Requirements § 430.86 Discovery. CMS and any party named in the notice issued under § 430.70 has the right to conduct discovery (including depositions) against opposing parties...

  16. 21 CFR 17.23 - Discovery.

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Discovery. 17.23 Section 17.23 Food and Drugs FOOD... HEARINGS § 17.23 Discovery. (a) No later than 60 days prior to the hearing, unless otherwise ordered by the..., depositions, and any forms of discovery, other than those permitted under paragraphs (a) and (e) of this...

  17. 45 CFR 96.65 - Discovery.

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 96.65 Section 96.65 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Hearing Procedure § 96.65 Discovery. The use of interrogatories, depositions, and other forms of discovery shall not be allowed. ...

  18. 7 CFR 1.322 - Discovery.

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Discovery. 1.322 Section 1.322 Agriculture Office of... Under the Program Fraud Civil Remedies Act of 1986 § 1.322 Discovery. (a) The following types of discovery are authorized: (1) Requests for production, inspection and photocopying of documents; (2...

  19. 45 CFR 1386.103 - Discovery.

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Discovery. 1386.103 Section 1386.103 Public... Hearing Procedures § 1386.103 Discovery. The Department and any party named in the Notice issued pursuant to § 1386.90 has the right to conduct discovery (including depositions) against opposing parties as...

  20. 45 CFR 79.21 - Discovery.

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 79.21 Section 79.21 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

  1. 49 CFR 31.21 - Discovery.

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Discovery. 31.21 Section 31.21 Transportation Office of the Secretary of Transportation PROGRAM FRAUD CIVIL REMEDIES § 31.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and...

  2. 12 CFR 308.520 - Discovery.

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Discovery. 308.520 Section 308.520 Banks and... PROCEDURE Program Fraud Civil Remedies and Procedures § 308.520 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...

  3. 47 CFR 1.729 - Discovery.

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Discovery. 1.729 Section 1.729..., and Reports Involving Common Carriers Formal Complaints § 1.729 Discovery. (a) Subject to paragraph (i... seek discovery of any non-privileged matter that is relevant to the material facts in dispute in the...

  4. 7 CFR 283.12 - Discovery.

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Discovery. 283.12 Section 283.12 Agriculture... of $50,000 or More § 283.12 Discovery. (a) Dispositions—(1) Motion for taking deposition. Only upon a... exist if the information sought appears reasonably calculated to lead to the discovery of admissible...

  5. Discovery of inhibitors of bacterial histidine kinases

    Velikova, N.R.

    2014-01-01

    Discovery of Inhibitors of Bacterial Histidine Kinases Summary

    The thesis is on novel antibacterial drug discovery (http://youtu.be/NRMWOGgeysM). Using structure-based and fragment-based drug discovery approach, we have identified small-molecule histidine-kinase

  6. 29 CFR 18.13 - Discovery methods.

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Discovery methods. 18.13 Section 18.13 Labor Office of the... ADMINISTRATIVE LAW JUDGES General § 18.13 Discovery methods. Parties may obtain discovery by one or more of the following methods: Depositions upon oral examination or written questions; written interrogatories...

  7. Glycoscience aids in biomarker discovery

    Serenus Hua1,2 & Hyun Joo An1,2,*

    2012-06-01

    Full Text Available The glycome consists of all glycans (or carbohydrates within abiological system, and modulates a wide range of important biologicalactivities, from protein folding to cellular communications.The mining of the glycome for disease markers representsa new paradigm for biomarker discovery; however, this effortis severely complicated by the vast complexity and structuraldiversity of glycans. This review summarizes recent developmentsin analytical technology and methodology as applied tothe fields of glycomics and glycoproteomics. Mass spectrometricstrategies for glycan compositional profiling are described, as arepotential refinements which allow structure-specific profiling.Analytical methods that can discern protein glycosylation at aspecific site of modification are also discussed in detail.Biomarker discovery applications are shown at each level ofanalysis, highlighting the key role that glycoscience can play inhelping scientists understand disease biology.

  8. Cyber-Enabled Scientific Discovery

    Chan, Tony; Jameson, Leland

    2007-01-01

    It is often said that numerical simulation is third in the group of three ways to explore modern science: theory, experiment and simulation. Carefully executed modern numerical simulations can, however, be considered at least as relevant as experiment and theory. In comparison to physical experimentation, with numerical simulation one has the numerically simulated values of every field variable at every grid point in space and time. In comparison to theory, with numerical simulation one can explore sets of very complex non-linear equations such as the Einstein equations that are very difficult to investigate theoretically. Cyber-enabled scientific discovery is not just about numerical simulation but about every possible issue related to scientific discovery by utilizing cyberinfrastructure such as the analysis and storage of large data sets, the creation of tools that can be used by broad classes of researchers and, above all, the education and training of a cyber-literate workforce

  9. Astrobiology, discovery, and societal impact

    Dick, Steven J

    2018-01-01

    The search for life in the universe, once the stuff of science fiction, is now a robust worldwide research program with a well-defined roadmap probing both scientific and societal issues. This volume examines the humanistic aspects of astrobiology, systematically discussing the approaches, critical issues, and implications of discovering life beyond Earth. What do the concepts of life and intelligence, culture and civilization, technology and communication mean in a cosmic context? What are the theological and philosophical implications if we find life - and if we do not? Steven J. Dick argues that given recent scientific findings, the discovery of life in some form beyond Earth is likely and so we need to study the possible impacts of such a discovery and formulate policies to deal with them. The remarkable and often surprising results are presented here in a form accessible to disciplines across the sciences, social sciences, and humanities.

  10. [Artificial Intelligence in Drug Discovery].

    Fujiwara, Takeshi; Kamada, Mayumi; Okuno, Yasushi

    2018-04-01

    According to the increase of data generated from analytical instruments, application of artificial intelligence(AI)technology in medical field is indispensable. In particular, practical application of AI technology is strongly required in "genomic medicine" and "genomic drug discovery" that conduct medical practice and novel drug development based on individual genomic information. In our laboratory, we have been developing a database to integrate genome data and clinical information obtained by clinical genome analysis and a computational support system for clinical interpretation of variants using AI. In addition, with the aim of creating new therapeutic targets in genomic drug discovery, we have been also working on the development of a binding affinity prediction system for mutated proteins and drugs by molecular dynamics simulation using supercomputer "Kei". We also have tackled for problems in a drug virtual screening. Our developed AI technology has successfully generated virtual compound library, and deep learning method has enabled us to predict interaction between compound and target protein.

  11. A quantum causal discovery algorithm

    Giarmatzi, Christina; Costa, Fabio

    2018-03-01

    Finding a causal model for a set of classical variables is now a well-established task—but what about the quantum equivalent? Even the notion of a quantum causal model is controversial. Here, we present a causal discovery algorithm for quantum systems. The input to the algorithm is a process matrix describing correlations between quantum events. Its output consists of different levels of information about the underlying causal model. Our algorithm determines whether the process is causally ordered by grouping the events into causally ordered non-signaling sets. It detects if all relevant common causes are included in the process, which we label Markovian, or alternatively if some causal relations are mediated through some external memory. For a Markovian process, it outputs a causal model, namely the causal relations and the corresponding mechanisms, represented as quantum states and channels. Our algorithm opens the route to more general quantum causal discovery methods.

  12. Discovery of Approximate Differential Dependencies

    Liu, Jixue; Kwashie, Selasi; Li, Jiuyong; Ye, Feiyue; Vincent, Millist

    2013-01-01

    Differential dependencies (DDs) capture the relationships between data columns of relations. They are more general than functional dependencies (FDs) and and the difference is that DDs are defined on the distances between values of two tuples, not directly on the values. Because of this difference, the algorithms for discovering FDs from data find only special DDs, not all DDs and therefore are not applicable to DD discovery. In this paper, we propose an algorithm to discover DDs from data fo...

  13. The discovery of the antiproton

    Chamberlain, Owen

    1989-01-01

    A number of groups of particle physicists competed to provide track evidence of the existence of Dirac's postulated antiproton in the mid-1950s. The work of the several teams is described briefly. The author describes the work of his own group on the Bevatron in more detail, and how they finally observed the antiproton. The article finishes with an assessment of the importance of this discovery. (UK)

  14. Gas reserves, discoveries and production

    Saniere, A.

    2006-01-01

    Between 2000 and 2004, new discoveries, located mostly in the Asia/Pacific region, permitted a 71% produced reserve replacement rate. The Middle East and the offshore sector represent a growing proportion of world gas production Non-conventional gas resources are substantial but are not exploited to any significant extent, except in the United States, where they account for 30% of U.S. gas production. (author)

  15. Sea Level Rise Data Discovery

    Quach, N.; Huang, T.; Boening, C.; Gill, K. M.

    2016-12-01

    Research related to sea level rise crosses multiple disciplines from sea ice to land hydrology. The NASA Sea Level Change Portal (SLCP) is a one-stop source for current sea level change information and data, including interactive tools for accessing and viewing regional data, a virtual dashboard of sea level indicators, and ongoing updates through a suite of editorial products that include content articles, graphics, videos, and animations. The architecture behind the SLCP makes it possible to integrate web content and data relevant to sea level change that are archived across various data centers as well as new data generated by sea level change principal investigators. The Extensible Data Gateway Environment (EDGE) is incorporated into the SLCP architecture to provide a unified platform for web content and science data discovery. EDGE is a data integration platform designed to facilitate high-performance geospatial data discovery and access with the ability to support multi-metadata standard specifications. EDGE has the capability to retrieve data from one or more sources and package the resulting sets into a single response to the requestor. With this unified endpoint, the Data Analysis Tool that is available on the SLCP can retrieve dataset and granule level metadata as well as perform geospatial search on the data. This talk focuses on the architecture that makes it possible to seamlessly integrate and enable discovery of disparate data relevant to sea level rise.

  16. A New Universe of Discoveries

    Córdova, France A.

    2016-01-01

    The convergence of emerging advances in astronomical instruments, computational capabilities and talented practitioners (both professional and civilian) is creating an extraordinary new environment for making numerous fundamental discoveries in astronomy, ranging from the nature of exoplanets to understanding the evolution of solar systems and galaxies. The National Science Foundation is playing a critical role in supporting, stimulating, and shaping these advances. NSF is more than an agency of government or a funding mechanism for the infrastructure of science. The work of NSF is a sacred trust that every generation of Americans makes to those of the next generation, that we will build on the body of knowledge we inherit and continue to push forward the frontiers of science. We never lose sight of NSF's obligation to "explore the unexplored" and inspire all of humanity with the wonders of discovery. As the only Federal agency dedicated to the support of basic research and education in all fields of science and engineering, NSF has empowered discoveries across a broad spectrum of scientific inquiry for more than six decades. The result is fundamental scientific research that has had a profound impact on our nation's innovation ecosystem and kept our nation at the very forefront of the world's science-and-engineering enterprise.

  17. Discovery of a Makemakean Moon

    Parker, Alex H.; Buie, Marc W.; Grundy, Will M.; Noll, Keith S.

    2016-01-01

    We describe the discovery of a satellite in orbit about the dwarf planet (136472) Makemake. This satellite, provisionally designated S/2015 (136472) 1, was detected in imaging data collected with the Hubble Space Telescope's Wide Field Camera 3 on UTC 2015 April 27 at 7.80 +/- 0.04 mag fainter than Makemake and at a separation of 0farcs57. It likely evaded detection in previous satellite searches due to a nearly edge-on orbital configuration, placing it deep within the glare of Makemake during a substantial fraction of its orbital period. This configuration would place Makemake and its satellite near a mutual event season. Insufficient orbital motion was detected to make a detailed characterization of its orbital properties, prohibiting a measurement of the system mass with the discovery data alone. Preliminary analysis indicates that if the orbit is circular, its orbital period must be longer than 12.4 days and must have a semimajor axis > or approx. = 21,000 km. We find that the properties of Makemake's moon suggest that the majority of the dark material detected in the system by thermal observations may not reside on the surface of Makemake, but may instead be attributable to S/2015 (136472) 1 having a uniform dark surface. This dark moon hypothesis can be directly tested with future James Webb Space Telescope observations. We discuss the implications of this discovery for the spin state, figure, and thermal properties of Makemake and the apparent ubiquity of trans-Neptunian dwarf planet satellites.

  18. Socratic Questioning-Guided Discovery

    M. Hakan Türkçapar

    2012-04-01

    Full Text Available “Socratic Method” is a way of teaching philosophical thinking and knowledge by asking questions which was used by antique period greek philosopher Socrates. Socrates was teaching knowledge to his followers by asking questions and the conversation between them was named “Socratic Dialogues”. In this meaning, no novel knowledge is taught to the individual but only what is formerly known is reminded and rediscovered. The form of socratic questioning which is used during the process of cognitive behavioral therapy is known as Guided Discovery. In this method it is aimed to make the client notice the piece of knowledge which he could notice but is not aware with a series of questions. Socratic method or guided discovery consists of several steps which are: Identifying the problem by listening to the client and making reflections, finding alternatives by examining and evaluating, reidentification by using the newly found information and questioning the old distorted belief and reaching to a conclusion and applying it. Question types used during these procedures are, questions for gaining information, questions revealing the meanings, questions revealing the beliefs, questions about behaviours during the similar past experiences, analyse questions and analytic synthesis questions. In order to make the patient feel understood it is important to be empathetic and summarising the problem during the interview. In this text, steps of Socratic Questioning-Guided Discovery will be reviewed with sample dialogues after eachstep. [JCBPR 2012; 1(1.000: 15-20

  19. Optogenetic Approaches to Drug Discovery in Neuroscience and Beyond.

    Zhang, Hongkang; Cohen, Adam E

    2017-07-01

    Recent advances in optogenetics have opened new routes to drug discovery, particularly in neuroscience. Physiological cellular assays probe functional phenotypes that connect genomic data to patient health. Optogenetic tools, in particular tools for all-optical electrophysiology, now provide a means to probe cellular disease models with unprecedented throughput and information content. These techniques promise to identify functional phenotypes associated with disease states and to identify compounds that improve cellular function regardless of whether the compound acts directly on a target or through a bypass mechanism. This review discusses opportunities and unresolved challenges in applying optogenetic techniques throughout the discovery pipeline - from target identification and validation, to target-based and phenotypic screens, to clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Superformed bands in atomic nuclei. A fascinating recent discovery

    Nazarewicz, W.; Szymanski, Z.

    1990-01-01

    The recent discovery of a new type of exotic state, the so-called superformed (SD) state in rapidly rotating, extremely distorted atomic nuclei has ushered in a new area of physics called high-spin spectroscopy. The measurement of discrete SD states at angular momenta lying in the 40 to 60 ℎ range is fast becoming a standard technique in nuclear γ-ray spectroscopy thanks to improved experimental skills and the introduction of multi-detector arrays. (orig.)

  1. Drug Discovery Gets a Boost from Data Science.

    Amaro, Rommie E

    2016-08-02

    In this issue of Structure, Schiebel et al. (2016) describe a workflow-driven approach to high-throughput X-ray crystallographic fragment screening and refinement. In doing so, they extend the applicability of X-ray crystallography as a primary fragment-screening tool and show how data science techniques can favorably impact drug discovery efforts. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Discovery of novel dengue virus NS5 methyltransferase non-nucleoside inhibitors by fragment-based drug design.

    Benmansour, Fatiha; Trist, Iuni; Coutard, Bruno; Decroly, Etienne; Querat, Gilles; Brancale, Andrea; Barral, Karine

    2017-01-05

    With the aim to help drug discovery against dengue virus (DENV), a fragment-based drug design approach was applied to identify ligands targeting a main component of DENV replication complex: the NS5 AdoMet-dependent mRNA methyltransferase (MTase) domain, playing an essential role in the RNA capping process. Herein, we describe the identification of new inhibitors developed using fragment-based, structure-guided linking and optimization techniques. Thermal-shift assay followed by a fragment-based X-ray crystallographic screening lead to the identification of three fragment hits binding DENV MTase. We considered linking two of them, which bind to proximal sites of the AdoMet binding pocket, in order to improve their potency. X-ray crystallographic structures and computational docking were used to guide the fragment linking, ultimately leading to novel series of non-nucleoside inhibitors of flavivirus MTase, respectively N-phenyl-[(phenylcarbamoyl)amino]benzene-1-sulfonamide and phenyl [(phenylcarbamoyl)amino]benzene-1-sulfonate derivatives, that show a 10-100-fold stronger inhibition of 2'-O-MTase activity compared to the initial fragments. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Mass Spectrometry–Based Biomarker Discovery: Toward a Global Proteome Index of Individuality

    Hawkridge, Adam M.; Muddiman, David C.

    2011-01-01

    Biomarker discovery and proteomics have become synonymous with mass spectrometry in recent years. Although this conflation is an injustice to the many essential biomolecular techniques widely used in biomarker-discovery platforms, it underscores the power and potential of contemporary mass spectrometry. Numerous novel and powerful technologies have been developed around mass spectrometry, proteomics, and biomarker discovery over the past 20 years to globally study complex proteomes (e.g., plasma). However, very few large-scale longitudinal studies have been carried out using these platforms to establish the analytical variability relative to true biological variability. The purpose of this review is not to cover exhaustively the applications of mass spectrometry to biomarker discovery, but rather to discuss the analytical methods and strategies that have been developed for mass spectrometry–based biomarker-discovery platforms and to place them in the context of the many challenges and opportunities yet to be addressed. PMID:20636062

  4. Use of machine learning approaches for novel drug discovery.

    Lima, Angélica Nakagawa; Philot, Eric Allison; Trossini, Gustavo Henrique Goulart; Scott, Luis Paulo Barbour; Maltarollo, Vinícius Gonçalves; Honorio, Kathia Maria

    2016-01-01

    The use of computational tools in the early stages of drug development has increased in recent decades. Machine learning (ML) approaches have been of special interest, since they can be applied in several steps of the drug discovery methodology, such as prediction of target structure, prediction of biological activity of new ligands through model construction, discovery or optimization of hits, and construction of models that predict the pharmacokinetic and toxicological (ADMET) profile of compounds. This article presents an overview on some applications of ML techniques in drug design. These techniques can be employed in ligand-based drug design (LBDD) and structure-based drug design (SBDD) studies, such as similarity searches, construction of classification and/or prediction models of biological activity, prediction of secondary structures and binding sites docking and virtual screening. Successful cases have been reported in the literature, demonstrating the efficiency of ML techniques combined with traditional approaches to study medicinal chemistry problems. Some ML techniques used in drug design are: support vector machine, random forest, decision trees and artificial neural networks. Currently, an important application of ML techniques is related to the calculation of scoring functions used in docking and virtual screening assays from a consensus, combining traditional and ML techniques in order to improve the prediction of binding sites and docking solutions.

  5. Asymmetric threat data mining and knowledge discovery

    Gilmore, John F.; Pagels, Michael A.; Palk, Justin

    2001-03-01

    Asymmetric threats differ from the conventional force-on- force military encounters that the Defense Department has historically been trained to engage. Terrorism by its nature is now an operational activity that is neither easily detected or countered as its very existence depends on small covert attacks exploiting the element of surprise. But terrorism does have defined forms, motivations, tactics and organizational structure. Exploiting a terrorism taxonomy provides the opportunity to discover and assess knowledge of terrorist operations. This paper describes the Asymmetric Threat Terrorist Assessment, Countering, and Knowledge (ATTACK) system. ATTACK has been developed to (a) data mine open source intelligence (OSINT) information from web-based newspaper sources, video news web casts, and actual terrorist web sites, (b) evaluate this information against a terrorism taxonomy, (c) exploit country/region specific social, economic, political, and religious knowledge, and (d) discover and predict potential terrorist activities and association links. Details of the asymmetric threat structure and the ATTACK system architecture are presented with results of an actual terrorist data mining and knowledge discovery test case shown.

  6. Computational discovery of extremal microstructure families

    Chen, Desai; Skouras, Mélina; Zhu, Bo; Matusik, Wojciech

    2018-01-01

    Modern fabrication techniques, such as additive manufacturing, can be used to create materials with complex custom internal structures. These engineered materials exhibit a much broader range of bulk properties than their base materials and are typically referred to as metamaterials or microstructures. Although metamaterials with extraordinary properties have many applications, designing them is very difficult and is generally done by hand. We propose a computational approach to discover families of microstructures with extremal macroscale properties automatically. Using efficient simulation and sampling techniques, we compute the space of mechanical properties covered by physically realizable microstructures. Our system then clusters microstructures with common topologies into families. Parameterized templates are eventually extracted from families to generate new microstructure designs. We demonstrate these capabilities on the computational design of mechanical metamaterials and present five auxetic microstructure families with extremal elastic material properties. Our study opens the way for the completely automated discovery of extremal microstructures across multiple domains of physics, including applications reliant on thermal, electrical, and magnetic properties. PMID:29376124

  7. Applying linked data approaches to pharmacology: Architectural decisions and implementation

    Gray, A.J.G; Groth, P.T.; Loizou, A.; Askjaer, S; Brenninkmeijer, C; Burger, K.; Chichester, C.; Evelo, C.T.; Goble, C.A.; Harland, L; Pettifier, S; Thompson, M.; Waagmeester, A; William, A.J

    2014-01-01

    The discovery of new medicines requires pharmacologists to interact with a number of information sources ranging from tabular data to scientific papers, and other specialized formats. In this application report, we describe a linked data platform for integrating multiple pharmacology datasets that

  8. Unsupervised action classification using space-time link analysis

    Liu, Haowei; Feris, Rogerio; Krüger, Volker

    2010-01-01

    In this paper we address the problem of unsupervised discovery of action classes in video data. Different from all existing methods thus far proposed for this task, we present a space-time link analysis approach which matches the performance of traditional unsupervised action categorization metho...

  9. DISCOVERY OF A MAKEMAKEAN MOON

    Parker, Alex H.; Buie, Marc W. [Southwest Research Institute, 1050 Walnut Street, Suite 300, Boulder, CO 80302 (United States); Grundy, Will M. [Lowell Observatory, Flagstaff, AZ (United States); Noll, Keith S., E-mail: aparker@boulder.swri.edu [NASA Goddard Space Flight Center, Greenbelt, MD (United States)

    2016-07-01

    We describe the discovery of a satellite in orbit about the dwarf planet (136472) Makemake. This satellite, provisionally designated S/2015 (136472) 1, was detected in imaging data collected with the Hubble Space Telescope ’s Wide Field Camera 3 on UTC 2015 April 27 at 7.80 ± 0.04 mag fainter than Makemake and at a separation of 0.″57. It likely evaded detection in previous satellite searches due to a nearly edge-on orbital configuration, placing it deep within the glare of Makemake during a substantial fraction of its orbital period. This configuration would place Makemake and its satellite near a mutual event season. Insufficient orbital motion was detected to make a detailed characterization of its orbital properties, prohibiting a measurement of the system mass with the discovery data alone. Preliminary analysis indicates that if the orbit is circular, its orbital period must be longer than 12.4 days and must have a semimajor axis ≳21,000 km. We find that the properties of Makemake’s moon suggest that the majority of the dark material detected in the system by thermal observations may not reside on the surface of Makemake, but may instead be attributable to S/2015 (136472) 1 having a uniform dark surface. This “dark moon hypothesis” can be directly tested with future James Webb Space Telescope observations. We discuss the implications of this discovery for the spin state, figure, and thermal properties of Makemake and the apparent ubiquity of trans-Neptunian dwarf planet satellites.

  10. Polar Domain Discovery with Sparkler

    Duerr, R.; Khalsa, S. J. S.; Mattmann, C. A.; Ottilingam, N. K.; Singh, K.; Lopez, L. A.

    2017-12-01

    The scientific web is vast and ever growing. It encompasses millions of textual, scientific and multimedia documents describing research in a multitude of scientific streams. Most of these documents are hidden behind forms which require user action to retrieve and thus can't be directly accessed by content crawlers. These documents are hosted on web servers across the world, most often on outdated hardware and network infrastructure. Hence it is difficult and time-consuming to aggregate documents from the scientific web, especially those relevant to a specific domain. Thus generating meaningful domain-specific insights is currently difficult. We present an automated discovery system (Figure 1) using Sparkler, an open-source, extensible, horizontally scalable crawler which facilitates high throughput and focused crawling of documents pertinent to a particular domain such as information about polar regions. With this set of highly domain relevant documents, we show that it is possible to answer analytical questions about that domain. Our domain discovery algorithm leverages prior domain knowledge to reach out to commercial/scientific search engines to generate seed URLs. Subject matter experts then annotate these seed URLs manually on a scale from highly relevant to irrelevant. We leverage this annotated dataset to train a machine learning model which predicts the `domain relevance' of a given document. We extend Sparkler with this model to focus crawling on documents relevant to that domain. Sparkler avoids disruption of service by 1) partitioning URLs by hostname such that every node gets a different host to crawl and by 2) inserting delays between subsequent requests. With an NSF-funded supercomputer Wrangler, we scaled our domain discovery pipeline to crawl about 200k polar specific documents from the scientific web, within a day.

  11. Guided Discovery with Socratic Questioning

    M. Hakan Türkçapar

    2015-04-01

    Full Text Available “The Socratic method” is a way of teaching philosophical thinking and knowledge by asking questions. It was first used by in ancient times by the Greek philosopher Socrates who taught his followers by asking questions; these conversations between them are known as “Socratic dialogues”. In this methodology, no new knowledge is taught to the individual; rather, the individual is guided to remember and rediscover what was formerly known through this process. The main method used in cognitive therapy is guided discovery. There are various methods of guided discovery in cognitive therapy. The form of verbal exchange between the therapist and client which is used during the process of cognitive behavioral therapy is known as “socratic questioning”. In this method the goal is to make the client rediscover, with a series of questions, a piece of knowledge which he could otherwise know but is not presently conscious of. The Socratic Questioning consists of several steps, including: identifying the problem by listening to the client and making reflections, finding alternatives by examining and evaluating, reidentification by using the newly rediscovered information and questioning the old distorted belief, and reaching a new conclusion and applying it. Question types used during these procedures are: questions for collecting information, questions revealing meanings, questions revealing beliefs, questions about behaviours during similar past experiences, analytic questions and analytic synthesis questions. In order to make the patient feel understood, it is important to be empathetic and summarize the problem during the interview. In this text, steps of Socratic Questioning-Guided Discovery will be reviewed with sample dialogues provided for each step. [JCBPR 2015; 4(1.000: 47-53

  12. A statistical model for telecommunication link design

    Yuen, J. H.

    1975-01-01

    An evaluation is conducted of the current telecommunication link design technique and a description is presented of an alternative method, called the probability distribution method (PDM), which is free of the disadvantages of the current technique while retaining its advantages. The PDM preserves the simplicity of the design control table (DCT) format. The use of the DCT as a management design control tool is continued. The telecommunication link margin probability density function used presents the probability of achieving any particular value of link performance. It is, therefore, possible to assess the performance risk and other tradeoffs.

  13. Knowledge discovery from data streams

    Gama, Joao

    2010-01-01

    Since the beginning of the Internet age and the increased use of ubiquitous computing devices, the large volume and continuous flow of distributed data have imposed new constraints on the design of learning algorithms. Exploring how to extract knowledge structures from evolving and time-changing data, Knowledge Discovery from Data Streams presents a coherent overview of state-of-the-art research in learning from data streams.The book covers the fundamentals that are imperative to understanding data streams and describes important applications, such as TCP/IP traffic, GPS data, sensor networks,

  14. Integration of Antibody Array Technology into Drug Discovery and Development.

    Huang, Wei; Whittaker, Kelly; Zhang, Huihua; Wu, Jian; Zhu, Si-Wei; Huang, Ruo-Pan

    Antibody arrays represent a high-throughput technique that enables the parallel detection of multiple proteins with minimal sample volume requirements. In recent years, antibody arrays have been widely used to identify new biomarkers for disease diagnosis or prognosis. Moreover, many academic research laboratories and commercial biotechnology companies are starting to apply antibody arrays in the field of drug discovery. In this review, some technical aspects of antibody array development and the various platforms currently available will be addressed; however, the main focus will be on the discussion of antibody array technologies and their applications in drug discovery. Aspects of the drug discovery process, including target identification, mechanisms of drug resistance, molecular mechanisms of drug action, drug side effects, and the application in clinical trials and in managing patient care, which have been investigated using antibody arrays in recent literature will be examined and the relevance of this technology in progressing this process will be discussed. Protein profiling with antibody array technology, in addition to other applications, has emerged as a successful, novel approach for drug discovery because of the well-known importance of proteins in cell events and disease development.

  15. Cloud computing approaches to accelerate drug discovery value chain.

    Garg, Vibhav; Arora, Suchir; Gupta, Chitra

    2011-12-01

    Continued advancements in the area of technology have helped high throughput screening (HTS) evolve from a linear to parallel approach by performing system level screening. Advanced experimental methods used for HTS at various steps of drug discovery (i.e. target identification, target validation, lead identification and lead validation) can generate data of the order of terabytes. As a consequence, there is pressing need to store, manage, mine and analyze this data to identify informational tags. This need is again posing challenges to computer scientists to offer the matching hardware and software infrastructure, while managing the varying degree of desired computational power. Therefore, the potential of "On-Demand Hardware" and "Software as a Service (SAAS)" delivery mechanisms cannot be denied. This on-demand computing, largely referred to as Cloud Computing, is now transforming the drug discovery research. Also, integration of Cloud computing with parallel computing is certainly expanding its footprint in the life sciences community. The speed, efficiency and cost effectiveness have made cloud computing a 'good to have tool' for researchers, providing them significant flexibility, allowing them to focus on the 'what' of science and not the 'how'. Once reached to its maturity, Discovery-Cloud would fit best to manage drug discovery and clinical development data, generated using advanced HTS techniques, hence supporting the vision of personalized medicine.

  16. Medical imaging was boosted by the discovery of artificial radioactivity

    Demarthon, F.; Dupuy-Maury, F.; Donnars, O.

    2002-01-01

    This article draws the history of medical imaging since the discovery of artificial radioactivity in 1934. The author reviews the PET (positron emission tomography) and MRI (magnetic resonance imaging) technologies and presents the recent progress in neuro-sciences that have been made possible by using these 2 technologies. Brain imaging has allowed to show: - the impact of emotions on logical mental processes and on mental performances, - the management of memory in the brain of talented quick reckoners, - the degeneration of neurons, and - the link between autism and the presence of structural and functional anomalies in the brain. (A.C.)

  17. Discovery of Five Probable Novae in M81

    Hornoch, K.; Errmann, R.; Sowicka, P.; Humphries, N.; Vaduvescu, O.

    2015-10-01

    We report the discovery of five probable novae in M81 on a co-added 2000-s narrow-band H-alpha CCD image taken with the 2.5-m Isaac Newton Telescope (INT) + WFC at La Palma under ~1.5" seeing on 2015 Oct. 14.198 UT. The new objects are well visible on the co-added image (see the finding charts linked below), but are not present on numerous narrow-band H-alpha archival images from the INT down to limiting magnitude as faint as H-alpha = 22.3.

  18. Semiconductor technology in protein kinase research and drug discovery: sensing a revolution.

    Bhalla, Nikhil; Di Lorenzo, Mirella; Estrela, Pedro; Pula, Giordano

    2017-02-01

    Since the discovery of protein kinase activity in 1954, close to 600 kinases have been discovered that have crucial roles in cell physiology. In several pathological conditions, aberrant protein kinase activity leads to abnormal cell and tissue physiology. Therefore, protein kinase inhibitors are investigated as potential treatments for several diseases, including dementia, diabetes, cancer and autoimmune and cardiovascular disease. Modern semiconductor technology has recently been applied to accelerate the discovery of novel protein kinase inhibitors that could become the standard-of-care drugs of tomorrow. Here, we describe current techniques and novel applications of semiconductor technologies in protein kinase inhibitor drug discovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. The discovery of uranium fission

    Brix, P.

    1990-01-01

    Uranium was discovered 200 years ago. Its radioactive character was first demonstrated in 1896 and two years later radium was extracted from uranium minerals. In 1911 studies with alpha rays from radioactive decay led to the unexpected discovery of the atomic nucleus. Exposure of beryllium to alpha rays yielded neutrons, first detected in 1932. Starting in 1934, neutron irradiation of uranium produced radioactive substances erroneously attributed to transuranium elements but with confusing properties. Painstaking experiments by chemists left no doubt on 17 December 1938 that barium was produced by these irradiations: the neutrons had split some uranium nuclei. The physics of the fission process was understood two weeks later; after a few months, neutron multiplication was found to be probable. This review deals with the eminent scientists involved, their successes, errors and disappointments, and the unexpected insights which occurred on the paths and detours of scientific research. It is, therefore, instructive also to discuss how fission was not discovered. The momentous discovery must be considered inevitable; the great tragedy was that Germany started World War II just at the time when the possibility of nuclear chain reactions and bombs became known. The consequences and anxieties that remain after 50 years of nuclear fission demand that mankind act with reason and conscience to maintain peace. (author)

  20. Astroparticle physics: puzzles and discoveries

    Berezinsky, V

    2008-01-01

    Puzzles often give birth to the great discoveries, the false discoveries sometimes stimulate the exiting ideas in theoretical physics. The historical examples of both are described in Introduction and in section 'Cosmological Puzzles'. From existing puzzles most attention is given to Ultra High Energy Cosmic Ray (UHECR) puzzle and to cosmological constant problem. The 40-years old UHECR problem consisted in absence of the sharp steepening in spectrum of extragalactic cosmic rays caused by interaction with CMB radiation. This steepening is known as Greisen-Zatsepin-Kuzmin (GZK) cutoff. It is demonstrated here that the features of interaction of cosmic ray protons with CMB are seen now in the spectrum in the form of the dip and beginning of the GZK cutoff. The most serious cosmological problem is caused by large vacuum energy of the known elementary-particle fields which exceeds at least by 45 orders of magnitude the cosmological vacuum energy. The various ideas put forward to solve this problem during last 40 years, have weaknesses and cannot be accepted as the final solution of this puzzle. The anthropic approach is discussed

  1. Current status and future prospects for enabling chemistry technology in the drug discovery process.

    Djuric, Stevan W; Hutchins, Charles W; Talaty, Nari N

    2016-01-01

    This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of "dangerous" reagents. Also featured are advances in the "computer-assisted drug design" area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities.

  2. [Frontiers in Live Bone Imaging Researches. Novel drug discovery by means of intravital bone imaging technology].

    Ishii, Masaru

    2015-06-01

    Recent advances in intravital bone imaging technology has enabled us to grasp the real cellular behaviors and functions in vivo , revolutionizing the field of drug discovery for novel therapeutics against intractable bone diseases. In this chapter, I introduce various updated information on pharmacological actions of several antibone resorptive agents, which could only be derived from advanced imaging techniques, and also discuss the future perspectives of this new trend in drug discovery.

  3. Current status and future prospects for enabling chemistry technology in the drug discovery process

    Djuric, Stevan W.; Hutchins, Charles W.; Talaty, Nari N.

    2016-01-01

    This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of “dangerous” reagents. Also featured are advances in the “computer-assisted drug design” area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities. PMID:27781094

  4. Automatic discovery of data-centric and artifact-centric processes

    Nooijen, E.H.J.; Dongen, van B.F.; Fahland, D.; La Rosa, M.; Soffer, P.

    2013-01-01

    Process discovery is a technique that allows for automatically discovering a process model from recorded executions of a process as it happens in reality. This technique has successfully been applied for classical processes where one process execution is constituted by a single case with a unique

  5. The discovery of radioactivity: the centenary

    Patil, S.K.

    1995-01-01

    In the last decade of the nineteenth century, a number of fundamental discoveries of outstanding importance were made unexpectedly which marked the beginning of a new era in physics. A cascade of spectacular discoveries began with the announcement of the discovery of x-rays by Roentgen followed by the discoveries, in quick succession, of radioactivity by Becquerel, of Zeeman effect, of electron by J.J. Thomson, and of polonium and radium by the Curies. Both x-rays and radioactivity have wide applications in scientific, medical and industrial fields and have made outstanding contribution to the advancement of human knowledge and welfare. Radioactivity is well known and no other discovery in the field of physics or chemistry has had a more profound effect on our fundamental knowledge of nature. Present article, on the occasion of the centenary of the discovery of radioactivity, makes an attempt to describe some glimpses of the history of radioactivity. (author). 59 refs

  6. Experimental techniques; Techniques experimentales

    Roussel-Chomaz, P. [GANIL CNRS/IN2P3, CEA/DSM, 14 - Caen (France)

    2007-07-01

    This lecture presents the experimental techniques, developed in the last 10 or 15 years, in order to perform a new class of experiments with exotic nuclei, where the reactions induced by these nuclei allow to get information on their structure. A brief review of the secondary beams production methods will be given, with some examples of facilities in operation or under project. The important developments performed recently on cryogenic targets will be presented. The different detection systems will be reviewed, both the beam detectors before the targets, and the many kind of detectors necessary to detect all outgoing particles after the reaction: magnetic spectrometer for the heavy fragment, detection systems for the target recoil nucleus, {gamma} detectors. Finally, several typical examples of experiments will be detailed, in order to illustrate the use of each detector either alone, or in coincidence with others. (author)

  7. Drugs + HIV, Learn the Link

    Full Text Available ... between drug misuse and HIV/AIDS and the discovery of promising treatment interventions for breaking the harmful ... requires the free Adobe Flash Player . NIH...Turning Discovery Into Health ®

  8. Discovery and Reuse of Open Datasets: An Exploratory Study

    Sara

    2016-07-01

    Full Text Available Objective: This article analyzes twenty cited or downloaded datasets and the repositories that house them, in order to produce insights that can be used by academic libraries to encourage discovery and reuse of research data in institutional repositories. Methods: Using Thomson Reuters’ Data Citation Index and repository download statistics, we identified twenty cited/downloaded datasets. We documented the characteristics of the cited/downloaded datasets and their corresponding repositories in a self-designed rubric. The rubric includes six major categories: basic information; funding agency and journal information; linking and sharing; factors to encourage reuse; repository characteristics; and data description. Results: Our small-scale study suggests that cited/downloaded datasets generally comply with basic recommendations for facilitating reuse: data are documented well; formatted for use with a variety of software; and shared in established, open access repositories. Three significant factors also appear to contribute to dataset discovery: publishing in discipline-specific repositories; indexing in more than one location on the web; and using persistent identifiers. The cited/downloaded datasets in our analysis came from a few specific disciplines, and tended to be funded by agencies with data publication mandates. Conclusions: The results of this exploratory research provide insights that can inform academic librarians as they work to encourage discovery and reuse of institutional datasets. Our analysis also suggests areas in which academic librarians can target open data advocacy in their communities in order to begin to build open data success stories that will fuel future advocacy efforts.

  9. [Fragment-based drug discovery: concept and aim].

    Tanaka, Daisuke

    2010-03-01

    Fragment-Based Drug Discovery (FBDD) has been recognized as a newly emerging lead discovery methodology that involves biophysical fragment screening and chemistry-driven fragment-to-lead stages. Although fragments, defined as structurally simple and small compounds (typically FBDD primarily turns our attention to weakly but specifically binding fragments (hit fragments) as the starting point of medicinal chemistry. Hit fragments are then promoted to more potent lead compounds through linking or merging with another hit fragment and/or attaching functional groups. Another positive aspect of FBDD is ligand efficiency. Ligand efficiency is a useful guide in screening hit selection and hit-to-lead phases to achieve lead-likeness. Owing to these features, a number of successful applications of FBDD to "undruggable targets" (where HTS and other lead identification methods failed to identify useful lead compounds) have been reported. As a result, FBDD is now expected to complement more conventional methodologies. This review, as an introduction of the following articles, will summarize the fundamental concepts of FBDD and will discuss its advantages over other conventional drug discovery approaches.

  10. Simulation with quantum mechanics/molecular mechanics for drug discovery.

    Barbault, Florent; Maurel, François

    2015-10-01

    Biological macromolecules, such as proteins or nucleic acids, are (still) molecules and thus they follow the same chemical rules that any simple molecule follows, even if their size generally renders accurate studies unhelpful. However, in the context of drug discovery, a detailed analysis of ligand association is required for understanding or predicting their interactions and hybrid quantum mechanics/molecular mechanics (QM/MM) computations are relevant tools to help elucidate this process. In this review, the authors explore the use of QM/MM for drug discovery. After a brief description of the molecular mechanics (MM) technique, the authors describe the subtractive and additive techniques for QM/MM computations. The authors then present several application cases in topics involved in drug discovery. QM/MM have been widely employed during the last decades to study chemical processes such as enzyme-inhibitor interactions. However, despite the enthusiasm around this area, plain MM simulations may be more meaningful than QM/MM. To obtain reliable results, the authors suggest fixing several keystone parameters according to the underlying chemistry of each studied system.

  11. [Application of Imaging Mass Spectrometry for Drug Discovery].

    Hayasaka, Takahiro

    2016-01-01

    Imaging mass spectrometry (IMS) can reveal the distribution of biomolecules on tissue sections. In this process, the biomolecules are directly ionized within tissue sections using matrix-assisted laser desorption/ionization, and then their distribution is visualized by pseudo-color based on the relative signal intensity. The biomolecules, such as fatty acids, phospholipids, glycolipids, peptides, proteins, and neurotransmitters, have been analyzed at a spatial resolution of 5 μm. A special instrument for IMS analysis was developed by Shimadzu. The IMS analysis does not require the labeling of biomolecules and is capable of analyzing all the ionized biomolecules. Interest in this method has expanded to many research fields, including biology, agriculture, medicine, and pharmacology. The technique is especially relevant to the drug discovery process. As practiced currently, drug discovery is expensive and time consuming, requiring the preparation of probes for each drug and its metabolites, followed by systematic probe tracking in animal models. The IMS technique is expected to overcome these drawbacks by revealing the distribution of drugs and their metabolites using only a single analysis. In this symposium, I introduced the methodology and applications of IMS and discussed the feasibility of its application to drug discovery in the near future.

  12. Fiftieth anniversary of major discoveries at the Cavendish Laboratory

    Sargent, B.W.

    1985-01-01

    This paper begins with some recollections of the Cavendish Laboratory of the University of Cambridge in the years 1928--30, which just preceded the discovery of the neutron and other major discoveries there in 1932--33. It then goes on to describe new developments in experimental techniques for accelerating, detecting, and counting charged particles such as protons and α particles in the Cavendish Laboratory which made possible the major discoveries by Chadwick, Blackett, and Cockcroft and Walton in 1932--33. The scintillation method was superseded by the linear amplifier and scale-of-two counter. Other experimental techniques described here include the original proportional counter, the cloud chamber triggered by coincident pulses in two Geiger--Mueller counters for the detection of cosmic rays, and a 700-kV voltage multiplier for the first transmutations by artificially accelerated hydrogen ions. Pioneer measurements on pair production of γ rays and annihilation radiation are discussed in terms of Dirac's relativistic theory of the electron

  13. mHealth Visual Discovery Dashboard.

    Fang, Dezhi; Hohman, Fred; Polack, Peter; Sarker, Hillol; Kahng, Minsuk; Sharmin, Moushumi; al'Absi, Mustafa; Chau, Duen Horng

    2017-09-01

    We present Discovery Dashboard, a visual analytics system for exploring large volumes of time series data from mobile medical field studies. Discovery Dashboard offers interactive exploration tools and a data mining motif discovery algorithm to help researchers formulate hypotheses, discover trends and patterns, and ultimately gain a deeper understanding of their data. Discovery Dashboard emphasizes user freedom and flexibility during the data exploration process and enables researchers to do things previously challenging or impossible to do - in the web-browser and in real time. We demonstrate our system visualizing data from a mobile sensor study conducted at the University of Minnesota that included 52 participants who were trying to quit smoking.

  14. Discovery of massive neutral vector mesons

    Anon.

    1976-01-01

    Personal accounts of the discovery of massive neutral vector mesons (psi particles) are given by researchers S. Ting, G. Goldhaber, and B. Richter. The double-arm spectrometer and the Cherenkov effect are explained in a technical note, and the solenoidal magnetic detector is discussed in an explanatory note for nonspecialists. Reprints of three papers in Physical Review Letters which announced the discovery of the particles are given: Experimental observation of a heavy particle J, Discovery of a narrow resonance in e + e - annihilation, and Discovery of a second narrow resonance in e + e - annihilation. A discussion of subsequent developments and scientific biographies of the three authors are also presented. 25 figures

  15. Object linking in repositories

    Eichmann, David (Editor); Beck, Jon; Atkins, John; Bailey, Bill

    1992-01-01

    This topic is covered in three sections. The first section explores some of the architectural ramifications of extending the Eichmann/Atkins lattice-based classification scheme to encompass the assets of the full life cycle of software development. A model is considered that provides explicit links between objects in addition to the edges connecting classification vertices in the standard lattice. The second section gives a description of the efforts to implement the repository architecture using a commercially available object-oriented database management system. Some of the features of this implementation are described, and some of the next steps to be taken to produce a working prototype of the repository are pointed out. In the final section, it is argued that design and instantiation of reusable components have competing criteria (design-for-reuse strives for generality, design-with-reuse strives for specificity) and that providing mechanisms for each can be complementary rather than antagonistic. In particular, it is demonstrated how program slicing techniques can be applied to customization of reusable components.

  16. Met1-linked Ubiquitination in Immune Signalling

    Fiil, Berthe Katrine; Gyrd-Hansen, Mads

    2014-01-01

    Methionine 1-linked ubiquitin chains (Met1-Ub), or linear ubiquitin, has emerged as a central post-translational modification in innate immune signalling. Molecular machinery that assembles, senses and, more recently, disassembles Met1-Ub has been identified, and technical advances have enabled...... identification of physiological substrates for Met1-Ub in response to activation of innate immune receptors. These discoveries have significantly advanced our understanding of how non-degradative ubiquitin modifications control pro-inflammatory responses mediated by nuclear factor κB and mitogen...

  17. Dynamic link: user's manual

    Harada, Hiroo; Asai, Kiyoshi; Kihara, Kazuhisa.

    1981-09-01

    The purpose of dynamic link facility is to link a load module dynamically only when it is used in execution time. The facility is very useful for development, execution and maintenance of a large scale computer program which is too big to be saved as one load module in main memory, or it is poor economy to save it due to many unused subroutines depending on an input. It is also useful for standardization and common utilization of programs. Standard usage of dynamic link facility of FACOM M-200 computer system, a software tool which analyzes the effect of dynamic link facility and application of dynamic link to nuclear codes are described. (author)

  18. In vivo brain microdialysis: advances in neuropsychopharmacology and drug discovery.

    Darvesh, Altaf S; Carroll, Richard T; Geldenhuys, Werner J; Gudelsky, Gary A; Klein, Jochen; Meshul, Charles K; Van der Schyf, Cornelis J

    2011-02-01

    INTRODUCTION: Microdialysis is an important in vivo sampling technique, useful in the assay of extracellular tissue fluid. The technique has both pre-clinical and clinical applications but is most widely used in neuroscience. The in vivo microdialysis technique allows measurement of neurotransmitters such as acetycholine (ACh), the biogenic amines including dopamine (DA), norepinephrine (NE) and serotonin (5-HT), amino acids such as glutamate (Glu) and gamma aminobutyric acid (GABA), as well as the metabolites of the aforementioned neurotransmitters, and neuropeptides in neuronal extracellular fluid in discrete brain regions of laboratory animals such as rodents and non-human primates. AREAS COVERED: In this review we present a brief overview of the principles and procedures related to in vivo microdialysis and detail the use of this technique in the pre-clinical measurement of drugs designed to be used in the treatment of chemical addiction, neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and as well as psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and schizophrenia. This review offers insight into the tremendous utility and versatility of this technique in pursuing neuropharmacological investigations as well its significant potential in rational drug discovery. EXPERT OPINION: In vivo microdialysis is an extremely versatile technique, routinely used in the neuropharmacological investigation of drugs used for the treatment of neurological disorders. This technique has been a boon in the elucidation of the neurochemical profile and mechanism of action of several classes of drugs especially their effects on neurotransmitter systems. The exploitation and development of this technique for drug discovery in the near future will enable investigational new drug candidates to be rapidly moved into the clinical trial stages and to market thus providing new successful therapies for neurological diseases

  19. Recent discoveries of anticancer flavonoids.

    Raffa, Demetrio; Maggio, Benedetta; Raimondi, Maria Valeria; Plescia, Fabiana; Daidone, Giuseppe

    2017-12-15

    In this review we report the recent advances in anticancer activity of the family of natural occurring flavonoids, covering the time span of the last five years. The bibliographic data will be grouped, on the basis of biological information, in two great categories: reports in which the extract plants bioactivity is reported and the identification of each flavonoid is present or not, and reports in which the anticancer activity is attributable to purified and identified flavonoids from plants. Wherever possible, the targets and mechanisms of action as well as the structure-activity relationships of the molecules will be reported. Also, in the review it was thoroughly investigated the recent discovery on flavonoids containing the 2-phenyl-4H-chromen-4-one system even if some examples of unusual flavonoids, bearing a non-aromatic B-ring or other ring condensed to the base structure are reported. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Specificity of discoveries in radiochemistry

    Krivomazov, A.N.

    1977-01-01

    The development of radiochemistry as a science is elucidated. On the basis of original papers and archives materials which have become available only recently, specific features of opening the law of radioactive displacements and isotopy of radioactive elements are presented in detail. A contribution of Hevesy, Russel, Fajans, and Soddy into the solution of this problem is considered; an important role of Rutherford in putting down the priority conflict is shown. Two stages of scientific generalization are singled out in the history of opening the law of radioactive displacements: the stage of the rules and the stage of the laws. On this basis the solutions of the priority problems have been reconsidered. It is shown that the history of radiochemistry is rich in discoveries which have undergone a relatively long evolution

  1. New perspectives on innovative drug discovery: an overview.

    Pan, Si Yuan; Pan, Shan; Yu, Zhi-Ling; Ma, Dik-Lung; Chen, Si-Bao; Fong, Wang-Fun; Han, Yi-Fan; Ko, Kam-Ming

    2010-01-01

    Despite advances in technology, drug discovery is still a lengthy, expensive, difficult, and inefficient process, with a low rate of success. Today, advances in biomedical science have brought about great strides in therapeutic interventions for a wide spectrum of diseases. The advent of biochemical techniques and cutting-edge bio/chemical technologies has made available a plethora of practical approaches to drug screening and design. In 2010, the total sales of the global pharmaceutical market will reach 600 billion US dollars and expand to over 975 billion dollars by 2013. The aim of this review is to summarize available information on contemporary approaches and strategies in the discovery of novel therapeutic agents, especially from the complementary and alternative medicines, including natural products and traditional remedies such as Chinese herbal medicine.

  2. Fluorescence lifetime assays: current advances and applications in drug discovery.

    Pritz, Stephan; Doering, Klaus; Woelcke, Julian; Hassiepen, Ulrich

    2011-06-01

    Fluorescence lifetime assays complement the portfolio of established assay formats available in drug discovery, particularly with the recent advances in microplate readers and the commercial availability of novel fluorescent labels. Fluorescence lifetime assists in lowering complexity of compound screening assays, affording a modular, toolbox-like approach to assay development and yielding robust homogeneous assays. To date, materials and procedures have been reported for biochemical assays on proteases, as well as on protein kinases and phosphatases. This article gives an overview of two assay families, distinguished by the origin of the fluorescence signal modulation. The pharmaceutical industry demands techniques with a robust, integrated compound profiling process and short turnaround times. Fluorescence lifetime assays have already helped the drug discovery field, in this sense, by enhancing productivity during the hit-to-lead and lead optimization phases. Future work will focus on covering other biochemical molecular modifications by investigating the detailed photo-physical mechanisms underlying the fluorescence signal.

  3. Twenty years on: the impact of fragments on drug discovery.

    Erlanson, Daniel A; Fesik, Stephen W; Hubbard, Roderick E; Jahnke, Wolfgang; Jhoti, Harren

    2016-09-01

    After 20 years of sometimes quiet growth, fragment-based drug discovery (FBDD) has become mainstream. More than 30 drug candidates derived from fragments have entered the clinic, with two approved and several more in advanced trials. FBDD has been widely applied in both academia and industry, as evidenced by the large number of papers from universities, non-profit research institutions, biotechnology companies and pharmaceutical companies. Moreover, FBDD draws on a diverse range of disciplines, from biochemistry and biophysics to computational and medicinal chemistry. As the promise of FBDD strategies becomes increasingly realized, now is an opportune time to draw lessons and point the way to the future. This Review briefly discusses how to design fragment libraries, how to select screening techniques and how to make the most of information gleaned from them. It also shows how concepts from FBDD have permeated and enhanced drug discovery efforts.

  4. Hybrid Monte Carlo algorithm with fat link fermion actions

    Kamleh, Waseem; Leinweber, Derek B.; Williams, Anthony G.

    2004-01-01

    The use of APE smearing or other blocking techniques in lattice fermion actions can provide many advantages. There are many variants of these fat link actions in lattice QCD currently, such as flat link irrelevant clover (FLIC) fermions. The FLIC fermion formalism makes use of the APE blocking technique in combination with a projection of the blocked links back into the special unitary group. This reunitarization is often performed using an iterative maximization of a gauge invariant measure. This technique is not differentiable with respect to the gauge field and thus prevents the use of standard Hybrid Monte Carlo simulation algorithms. The use of an alternative projection technique circumvents this difficulty and allows the simulation of dynamical fat link fermions with standard HMC and its variants. The necessary equations of motion for FLIC fermions are derived, and some initial simulation results are presented. The technique is more general however, and is straightforwardly applicable to other smearing techniques or fat link actions

  5. Archeologia e Risorgimento. La scoperta degli Etruschi a Bologna / Archaeology and Risorgimento. The discovery of the Etruscans in Bologna

    Sassatelli, Giuseppe

    2011-01-01

    During the italian Risorgimento and unification periods there was a link between the idea of national unity, the exploitation of urban identities and archeology, in particular the archeology of sites belonging to inhabitance of Italy in pre-Roman times. The discoveries concerning the Etruscans particularly influenced historical events and projects related to the future of the newly unified Italy. This paper analyzes the discovery of the Etruscans in Bologna and the consequences with respect t...

  6. A Tale of Two Discoveries: Comparing the Usability of Summon and EBSCO Discovery Service

    Foster, Anita K.; MacDonald, Jean B.

    2013-01-01

    Web-scale discovery systems are gaining momentum among academic libraries as libraries seek a means to provide their users with a one-stop searching experience. Illinois State University's Milner Library found itself in the unique position of having access to two distinct discovery products, EBSCO Discovery Service and Serials Solutions' Summon.…

  7. Discovery Mondays - 'Particle tracks: Seeing the invisible'

    2007-01-01

    Simulation of particle tracks in the CMS detector. How can you 'see' something as infinitesimal and fleeting as an elementary particle that defeats even the most powerful microscope? Well, physicists have detectors to snoop on them. Unlike biologists looking at bacteria, physicists don't see the particles themselves. They study their impact on sensitive materials as they pass through them at ultra high speed, a bit like seeing plane vapour trails in a clear sky. At the next Discovery Monday you will be able to find out about the different methods used at CERN to detect particles. There will be demonstrations of the cloud chamber, where particles leave tell-tale evidence of their passage in tracks of droplets. You will also learn about past and current particle track detection techniques and how the tracks are reconstructed into magnificent composite images. Don't miss this opportunity to learn about the various ways of 'seeing' particles. The event will be conducted in French. Come along to the Microcosm ...

  8. The Higgs Boson Search and Discovery

    Bernardi, Gregorio

    2016-01-01

    We present a brief account of the search for the Higgs boson at the three major colliders that have operated over the last three decades: LEP, the Tevatron, and the LHC. The experimental challenges encountered stemmed from the distinct event phenomenology as determined by the colliders energy and the possible values for the Higgs boson mass, and from the capability of these colliders to deliver as much collision data as possible to fully explore the mass spectrum within their reach. Focusing more on the hadron collider searches during the last decade, we discuss how the search for the Higgs boson was advanced through mastering the experimental signatures of standard theory backgrounds, through the comprehensive utilization of the features of the detectors involved in the searches, and by means of advanced data analysis techniques. The search culminated in 2012 with the discovery, by the ATLAS and CMS collaborations, of a Higgs-like particle with mass close to 125 GeV, confirmed more recently to have propertie...

  9. Exploring relation types for literature-based discovery.

    Preiss, Judita; Stevenson, Mark; Gaizauskas, Robert

    2015-09-01

    Literature-based discovery (LBD) aims to identify "hidden knowledge" in the medical literature by: (1) analyzing documents to identify pairs of explicitly related concepts (terms), then (2) hypothesizing novel relations between pairs of unrelated concepts that are implicitly related via a shared concept to which both are explicitly related. Many LBD approaches use simple techniques to identify semantically weak relations between concepts, for example, document co-occurrence. These generate huge numbers of hypotheses, difficult for humans to assess. More complex techniques rely on linguistic analysis, for example, shallow parsing, to identify semantically stronger relations. Such approaches generate fewer hypotheses, but may miss hidden knowledge. The authors investigate this trade-off in detail, comparing techniques for identifying related concepts to discover which are most suitable for LBD. A generic LBD system that can utilize a range of relation types was developed. Experiments were carried out comparing a number of techniques for identifying relations. Two approaches were used for evaluation: replication of existing discoveries and the "time slicing" approach.(1) RESULTS: Previous LBD discoveries could be replicated using relations based either on document co-occurrence or linguistic analysis. Using relations based on linguistic analysis generated many fewer hypotheses, but a significantly greater proportion of them were candidates for hidden knowledge. The use of linguistic analysis-based relations improves accuracy of LBD without overly damaging coverage. LBD systems often generate huge numbers of hypotheses, which are infeasible to manually review. Improving their accuracy has the potential to make these systems significantly more usable. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.

  10. The use of web ontology languages and other semantic web tools in drug discovery.

    Chen, Huajun; Xie, Guotong

    2010-05-01

    To optimize drug development processes, pharmaceutical companies require principled approaches to integrate disparate data on a unified infrastructure, such as the web. The semantic web, developed on the web technology, provides a common, open framework capable of harmonizing diversified resources to enable networked and collaborative drug discovery. We survey the state of art of utilizing web ontologies and other semantic web technologies to interlink both data and people to support integrated drug discovery across domains and multiple disciplines. Particularly, the survey covers three major application categories including: i) semantic integration and open data linking; ii) semantic web service and scientific collaboration and iii) semantic data mining and integrative network analysis. The reader will gain: i) basic knowledge of the semantic web technologies; ii) an overview of the web ontology landscape for drug discovery and iii) a basic understanding of the values and benefits of utilizing the web ontologies in drug discovery. i) The semantic web enables a network effect for linking open data for integrated drug discovery; ii) The semantic web service technology can support instant ad hoc collaboration to improve pipeline productivity and iii) The semantic web encourages publishing data in a semantic way such as resource description framework attributes and thus helps move away from a reliance on pure textual content analysis toward more efficient semantic data mining.

  11. Accounting for discovery bias in genomic prediction

    Our objective was to evaluate an approach to mitigating discovery bias in genomic prediction. Accuracy may be improved by placing greater emphasis on regions of the genome expected to be more influential on a trait. Methods emphasizing regions result in a phenomenon known as “discovery bias” if info...

  12. Intraday Price Discovery in Fragmented Markets

    S.R. Ozturk (Sait); M. van der Wel (Michel); D.J.C. van Dijk (Dick)

    2014-01-01

    textabstractFor many assets, trading is fragmented across multiple exchanges. Price discovery measures summarize the informativeness of trading on each venue for discovering the asset’s true underlying value. We explore intraday variation in price discovery using a structural model with

  13. 40 CFR 209.22 - Other discovery.

    2010-07-01

    ... PRACTICE GOVERNING PROCEEDINGS UNDER THE NOISE CONTROL ACT OF 1972 Rules of Practice Governing Hearings for Orders Issued Under Section 11(d) of the Noise Control Act § 209.22 Other discovery. (a) Further... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Other discovery. 209.22 Section 209.22...

  14. 12 CFR 509.102 - Discovery.

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Discovery. 509.102 Section 509.102 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY RULES OF PRACTICE AND PROCEDURE IN ADJUDICATORY PROCEEDINGS Local Rules § 509.102 Discovery. (a) In general. A party may take the deposition of an...

  15. 7 CFR 283.28 - Discovery.

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Discovery. 283.28 Section 283.28 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE... Appeals of QC Claims of Less Than $50,000 § 283.28 Discovery. Upon motion and as ordered by the ALJ...

  16. 43 CFR 4.826 - Discovery.

    2010-10-01

    ... Review Under Part 17 of This Title-Nondiscrimination in Federally Assisted Programs of the Department of... the person from whom discovery is sought, and for good cause shown, the administrative law judge may make any order which justice requires to limit or condition discovery in order to protect a party or...

  17. Collagen cross linking: Current perspectives

    Srinivas K Rao

    2013-01-01

    Full Text Available Keratoconus is a common ectatic disorder occurring in more than 1 in 1,000 individuals. The condition typically starts in adolescence and early adulthood. It is a disease with an uncertain cause and its progression is unpredictable, but in extreme cases, vision deteriorates and can require corneal transplant surgery. Corneal collagen cross-linking (CCL with riboflavin (C3R is a recent treatment option that can enhance the rigidity of the cornea and prevent disease progression. Since its inception, the procedure has evolved with newer instrumentation, surgical techniques, and is also now performed for expanded indications other than keratoconus. With increasing experience, newer guidelines regarding optimization of patient selection, the spectrum of complications and their management, and combination procedures are being described. This article in conjunction with the others in this issue, will try and explore the uses of collagen cross-linking (CXL in its current form.

  18. Visualisierung von typisierten Links in Linked Data

    Georg Neubauer

    2017-09-01

    Full Text Available Das Themengebiet der Arbeit behandelt Visualisierungen von typisierten Links in Linked Data. Die wissenschaftlichen Gebiete, die im Allgemeinen den Inhalt des Beitrags abgrenzen, sind das Semantic Web, das Web of Data und Informationsvisualisierung. Das Semantic Web, das von Tim Berners Lee 2001 erfunden wurde, stellt eine Erweiterung zum World Wide Web (Web 2.0 dar. Aktuelle Forschungen beziehen sich auf die Verknüpfbarkeit von Informationen im World Wide Web. Um es zu ermöglichen, solche Verbindungen wahrnehmen und verarbeiten zu können sind Visualisierungen die wichtigsten Anforderungen als Hauptteil der Datenverarbeitung. Im Zusammenhang mit dem Sematic Web werden Repräsentationen von zuhammenhängenden Informationen anhand von Graphen gehandhabt. Der Grund des Entstehens dieser Arbeit ist in erster Linie die Beschreibung der Gestaltung von Linked Data-Visualisierungskonzepten, deren Prinzipien im Rahmen einer theoretischen Annäherung eingeführt werden. Anhand des Kontexts führt eine schrittweise Erweiterung der Informationen mit dem Ziel, praktische Richtlinien anzubieten, zur Vernetzung dieser ausgearbeiteten Gestaltungsrichtlinien. Indem die Entwürfe zweier alternativer Visualisierungen einer standardisierten Webapplikation beschrieben werden, die Linked Data als Netzwerk visualisiert, konnte ein Test durchgeführt werden, der deren Kompatibilität zum Inhalt hatte. Der praktische Teil behandelt daher die Designphase, die Resultate, und zukünftige Anforderungen des Projektes, die durch die Testung ausgearbeitet wurden.

  19. Knowledge Discovery and Data Mining in Iran's Climatic Researches

    Karimi, Mostafa

    2013-04-01

    Advances in measurement technology and data collection is the database gets larger. Large databases require powerful tools for analysis data. Iterative process of acquiring knowledge from information obtained from data processing is done in various forms in all scientific fields. However, when the data volume large, and many of the problems the Traditional methods cannot respond. in the recent years, use of databases in various scientific fields, especially atmospheric databases in climatology expanded. in addition, increases in the amount of data generated by the climate models is a challenge for analysis of it for extraction of hidden pattern and knowledge. The approach to this problem has been made in recent years uses the process of knowledge discovery and data mining techniques with the use of the concepts of machine learning, artificial intelligence and expert (professional) systems is overall performance. Data manning is analytically process for manning in massive volume data. The ultimate goal of data mining is access to information and finally knowledge. climatology is a part of science that uses variety and massive volume data. Goal of the climate data manning is Achieve to information from variety and massive atmospheric and non-atmospheric data. in fact, Knowledge Discovery performs these activities in a logical and predetermined and almost automatic process. The goal of this research is study of uses knowledge Discovery and data mining technique in Iranian climate research. For Achieve This goal, study content (descriptive) analysis and classify base method and issue. The result shown that in climatic research of Iran most clustering, k-means and wards applied and in terms of issues precipitation and atmospheric circulation patterns most introduced. Although several studies in geography and climate issues with statistical techniques such as clustering and pattern extraction is done, Due to the nature of statistics and data mining, but cannot say for

  20. The discovery of the periodic table as a case of simultaneous discovery.

    Scerri, Eric

    2015-03-13

    The article examines the question of priority and simultaneous discovery in the context of the discovery of the periodic system. It is argued that rather than being anomalous, simultaneous discovery is the rule. Moreover, I argue that the discovery of the periodic system by at least six authors in over a period of 7 years represents one of the best examples of a multiple discovery. This notion is supported by a new view of the evolutionary development of science through a mechanism that is dubbed Sci-Gaia by analogy with Lovelock's Gaia hypothesis. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  1. Automated discovery systems and the inductivist controversy

    Giza, Piotr

    2017-09-01

    The paper explores possible influences that some developments in the field of branches of AI, called automated discovery and machine learning systems, might have upon some aspects of the old debate between Francis Bacon's inductivism and Karl Popper's falsificationism. Donald Gillies facetiously calls this controversy 'the duel of two English knights', and claims, after some analysis of historical cases of discovery, that Baconian induction had been used in science very rarely, or not at all, although he argues that the situation has changed with the advent of machine learning systems. (Some clarification of terms machine learning and automated discovery is required here. The key idea of machine learning is that, given data with associated outcomes, software can be trained to make those associations in future cases which typically amounts to inducing some rules from individual cases classified by the experts. Automated discovery (also called machine discovery) deals with uncovering new knowledge that is valuable for human beings, and its key idea is that discovery is like other intellectual tasks and that the general idea of heuristic search in problem spaces applies also to discovery tasks. However, since machine learning systems discover (very low-level) regularities in data, throughout this paper I use the generic term automated discovery for both kinds of systems. I will elaborate on this later on). Gillies's line of argument can be generalised: thanks to automated discovery systems, philosophers of science have at their disposal a new tool for empirically testing their philosophical hypotheses. Accordingly, in the paper, I will address the question, which of the two philosophical conceptions of scientific method is better vindicated in view of the successes and failures of systems developed within three major research programmes in the field: machine learning systems in the Turing tradition, normative theory of scientific discovery formulated by Herbert Simon

  2. Techniques de combustion Combustin Techniques

    Perthuis E.

    2006-11-01

    Full Text Available L'efficacité d'un processus de chauffage par flamme est étroitement liée à la maîtrise des techniques de combustion. Le brûleur, organe essentiel de l'équipement de chauffe, doit d'une part assurer une combustion complète pour utiliser au mieux l'énergie potentielle du combustible et, d'autre part, provoquer dans le foyer les conditions aérodynamiques les plus propices oux transferts de chaleur. En s'appuyant sur les études expérimentales effectuées à la Fondation de Recherches Internationales sur les Flammes (FRIF, au Groupe d'Étude des Flammes de Gaz Naturel (GEFGN et à l'Institut Français du Pétrole (IFP et sur des réalisations industrielles, on présente les propriétés essentielles des flammes de diffusion aux combustibles liquides et gazeux obtenues avec ou sans mise en rotation des fluides, et leurs répercussions sur les transferts thermiques. La recherche des températures de combustion élevées conduit à envisager la marche à excès d'air réduit, le réchauffage de l'air ou son enrichissement à l'oxygène. Par quelques exemples, on évoque l'influence de ces paramètres d'exploitation sur l'économie possible en combustible. The efficiency of a flame heating process is closely linked ta the mastery of, combustion techniques. The burner, an essential element in any heating equipment, must provide complete combustion sa as to make optimum use of the potential energy in the fuel while, at the same time, creating the most suitable conditions for heat transfers in the combustion chamber. On the basis of experimental research performed by FRIF, GEFGN and IFP and of industrial achievements, this article describesthe essential properties of diffusion flames fed by liquid and gaseous fuels and produced with or without fluid swirling, and the effects of such flames on heat transfers. The search for high combustion temperatures means that consideration must be given to operating with reduced excess air, heating the air or

  3. Swift: 10 Years of Discovery

    2014-12-01

    The conference Swift: 10 years of discovery was held in Roma at La Sapienza University on Dec. 2-5 2014 to celebrate 10 years of Swift successes. Thanks to a large attendance and a lively program, it provided the opportunity to review recent advances of our knowledge of the high-energy transient Universe both from the observational and theoretical sides. When Swift was launched on November 20, 2004, its prime objective was to chase Gamma-Ray Bursts and deepen our knowledge of these cosmic explosions. And so it did, unveiling the secrets of long and short GRBs. However, its multi-wavelength instrumentation and fast scheduling capabilities made it the most versatile mission ever flown. Besides GRBs, Swift has observed, and contributed to our understanding of, an impressive variety of targets including AGNs, supernovae, pulsars, microquasars, novae, variable stars, comets, and much more. Swift is continuously discovering rare and surprising events distributed over a wide range of redshifts, out to the most distant transient objects in the Universe. Such a trove of discoveries has been addressed during the conference with sessions dedicated to each class of events. Indeed, the conference in Rome was a spectacular celebration of the Swift 10th anniversary. It included sessions on all types of transient and steady sources. Top scientists from around the world gave invited and contributed talks. There was a large poster session, sumptuous lunches, news interviews and a glorious banquet with officials attending from INAF and ASI. All the presentations, as well as several conference pictures, can be found in the conference website (http://www.brera.inaf.it/Swift10/Welcome.html). These proceedings have been collected owing to the efforts of Paolo D’Avanzo who has followed each paper from submission to final acceptance. Our warmest thanks to Paolo for all his work. The Conference has been made possible by the support from La Sapienza University as well as from the ARAP

  4. Linking open vocabularies

    Greifender, Elke; Seadle, Michael

    2013-01-01

    Linked Data (LD), Linked Open Data (LOD) and generating a web of data, present the new knowledge sharing frontier. In a philosophical context, LD is an evolving environment that reflects humankinds' desire to understand the world by drawing on the latest technologies and capabilities of the time. LD, while seemingly a new phenomenon did not emerge overnight; rather it represents the natural progression by which knowledge structures are developed, used, and shared. Linked Open Vocabularies is a significant trajectory of LD. Linked Open Vocabularies targets vocabularies that have traditionally b

  5. From the nucleus discovery to DWBA; De la decouverte du noyau a la DWBA

    Fernandez, B. [Ecole Joliot Curie, 33 - Gradignan (France)

    2007-07-01

    The author presents a brief review of the main events in the field of nuclear reactions that are acknowledged as milestones because of their importance due to either experimental setting or physical interpretation. It is shown that the pace of discoveries has been strongly dependent on the technical progress in detection means at the beginning of nuclear physics and now is linked to the development of simulation means. The discovery of the neutron, the development of the Geiger counter, the theory of the compound nucleus or the first direct reactions are among these milestones.

  6. Discovery of pyridine-based agrochemicals by using Intermediate Derivatization Methods.

    Guan, Ai-Ying; Liu, Chang-Ling; Sun, Xu-Feng; Xie, Yong; Wang, Ming-An

    2016-02-01

    Pyridine-based compounds have been playing a crucial role as agrochemicals or pesticides including fungicides, insecticides/acaricides and herbicides, etc. Since most of the agrochemicals listed in the Pesticide Manual were discovered through screening programs that relied on trial-and-error testing and new agrochemical discovery is not benefiting as much from the in silico new chemical compound identification/discovery techniques used in pharmaceutical research, it has become more important to find new methods to enhance the efficiency of discovering novel lead compounds in the agrochemical field to shorten the time of research phases in order to meet changing market requirements. In this review, we selected 18 representative known agrochemicals containing a pyridine moiety and extrapolate their discovery from the perspective of Intermediate Derivatization Methods in the hope that this approach will have greater appeal to researchers engaged in the discovery of agrochemicals and/or pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. High throughput electrophysiology: new perspectives for ion channel drug discovery

    Willumsen, Niels J; Bech, Morten; Olesen, Søren-Peter

    2003-01-01

    Proper function of ion channels is crucial for all living cells. Ion channel dysfunction may lead to a number of diseases, so-called channelopathies, and a number of common diseases, including epilepsy, arrhythmia, and type II diabetes, are primarily treated by drugs that modulate ion channels....... A cornerstone in current drug discovery is high throughput screening assays which allow examination of the activity of specific ion channels though only to a limited extent. Conventional patch clamp remains the sole technique with sufficiently high time resolution and sensitivity required for precise and direct...... characterization of ion channel properties. However, patch clamp is a slow, labor-intensive, and thus expensive, technique. New techniques combining the reliability and high information content of patch clamping with the virtues of high throughput philosophy are emerging and predicted to make a number of ion...

  8. Mathematical models in biological discovery

    Walter, Charles

    1977-01-01

    When I was asked to help organize an American Association for the Advancement of Science symposium about how mathematical models have con­ tributed to biology, I agreed immediately. The subject is of immense importance and wide-spread interest. However, too often it is discussed in biologically sterile environments by "mutual admiration society" groups of "theoreticians", many of whom have never seen, and most of whom have never done, an original scientific experiment with the biolog­ ical materials they attempt to describe in abstract (and often prejudiced) terms. The opportunity to address the topic during an annual meeting of the AAAS was irresistable. In order to try to maintain the integrity ;,f the original intent of the symposium, it was entitled, "Contributions of Mathematical Models to Biological Discovery". This symposium was organized by Daniel Solomon and myself, held during the 141st annual meeting of the AAAS in New York during January, 1975, sponsored by sections G and N (Biological and Medic...

  9. The Discovery of Dabigatran Etexilate

    Joanne evan Ryn

    2013-02-01

    Full Text Available Thromboembolic disease is a major cause of mortality and morbidity in the developed world and is caused by an excessive stimulation of coagulation. Thrombin is a key serine protease in the coagulation cascade and numerous efforts have been made to develop safe and effective orally active direct thrombin inhibitors (DTIs. Current anticoagulant therapy includes the use of indirect thrombin inhibitors (e.g. heparins, low-molecular-weight-heparins [LMWHs] and vitamin K antagonists (VKA such as warfarin. However there are several caveats in the clinical use of these agents including narrow therapeutic window, parenteral delivery, and food- and drug-drug interactions. Dabigatran is a synthetic, reversible DTI with high affinity and specificity for its target binding both free and clot-bound thrombin, and offers a favorable pharmacokinetic profile. Large randomized clinical trials have demonstrated that dabigatran provides comparable or superior thromboprophylaxis in multiple thromboembolic disease indications compared to standard of care. This minireview will highlight the discovery and development of dabigatran, the first in a class of new oral anticoagulant (NOAC agents to be licensed worldwide for the prevention of thromboembolism in the setting of orthopedic surgery and stroke prevent in atrial fibrillation.

  10. West Nile Virus Drug Discovery

    Siew Pheng Lim

    2013-12-01

    Full Text Available The outbreak of West Nile virus (WNV in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug discovery. A number of approaches have been used to search for inhibitors of WNV, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. These efforts have yielded inhibitors of viral or cellular factors that are critical for viral replication. For small molecule inhibitors, no promising preclinical candidate has been developed; most of the inhibitors could not even be advanced to the stage of hit-to-lead optimization due to their poor drug-like properties. However, several inhibitors developed for related members of the family Flaviviridae, such as dengue virus and hepatitis C virus, exhibited cross-inhibition of WNV, suggesting the possibility to re-purpose these antivirals for WNV treatment. Most promisingly, therapeutic antibodies have shown excellent efficacy in mouse model; one of such antibodies has been advanced into clinical trial. The knowledge accumulated during the past fifteen years has provided better rationale for the ongoing WNV and other flavivirus antiviral development.

  11. NIF Discovery Science Eagle Nebula

    Kane, Jave; Martinez, David; Pound, Marc; Heeter, Robert; Casner, Alexis; Villette, Bruno; Mancini, Roberto

    2017-10-01

    The University of Maryland and and LLNL are investigating the origin and dynamics of the famous Pillars of the Eagle Nebula and similar parsec-scale structures at the boundaries of HII regions in molecular hydrogen clouds. The National Ignition Facility (NIF) Discovery Science program Eagle Nebula has performed NIF shots to study models of pillar formation. The shots feature a new long-duration x-ray source, in which multiple hohlraums mimicking a cluster of stars are driven with UV light in series for 10 to 15 ns each to create a 30 to 60 ns output x-ray pulse. The source generates deeply nonlinear hydrodynamics in the Eagle science package, a structure of dense plastic and foam mocking up a molecular cloud containing a dense core. Omega EP and NIF shots have validated the source concept, showing that earlier hohlraums do not compromise later ones by preheat or by ejecting ablated plumes that deflect later beams. The NIF shots generated radiographs of shadowing-model pillars, and also showed evidence that cometary structures can be generated. The velocity and column density profiles of the NIF shadowing and cometary pillars have been compared with observations of the Eagle Pillars made at the millimeter-wave BIMA and CARMA observatories. Prepared by LLNL under Contract DE-AC52-07NA27344.

  12. Mass spectrometry imaging enriches biomarker discovery approaches with candidate mapping.

    Scott, Alison J; Jones, Jace W; Orschell, Christie M; MacVittie, Thomas J; Kane, Maureen A; Ernst, Robert K

    2014-01-01

    Integral to the characterization of radiation-induced tissue damage is the identification of unique biomarkers. Biomarker discovery is a challenging and complex endeavor requiring both sophisticated experimental design and accessible technology. The resources within the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Consortium, Medical Countermeasures Against Radiological Threats (MCART), allow for leveraging robust animal models with novel molecular imaging techniques. One such imaging technique, MALDI (matrix-assisted laser desorption ionization) mass spectrometry imaging (MSI), allows for the direct spatial visualization of lipids, proteins, small molecules, and drugs/drug metabolites-or biomarkers-in an unbiased manner. MALDI-MSI acquires mass spectra directly from an intact tissue slice in discrete locations across an x, y grid that are then rendered into a spatial distribution map composed of ion mass and intensity. The unique mass signals can be plotted to generate a spatial map of biomarkers that reflects pathology and molecular events. The crucial unanswered questions that can be addressed with MALDI-MSI include identification of biomarkers for radiation damage that reflect the response to radiation dose over time and the efficacy of therapeutic interventions. Techniques in MALDI-MSI also enable integration of biomarker identification among diverse animal models. Analysis of early, sublethally irradiated tissue injury samples from diverse mouse tissues (lung and ileum) shows membrane phospholipid signatures correlated with histological features of these unique tissues. This paper will discuss the application of MALDI-MSI for use in a larger biomarker discovery pipeline.

  13. Machine-assisted discovery of relationships in astronomy

    Graham, Matthew J.; Djorgovski, S. G.; Mahabal, Ashish A.; Donalek, Ciro; Drake, Andrew J.

    2013-05-01

    High-volume feature-rich data sets are becoming the bread-and-butter of 21st century astronomy but present significant challenges to scientific discovery. In particular, identifying scientifically significant relationships between sets of parameters is non-trivial. Similar problems in biological and geosciences have led to the development of systems which can explore large parameter spaces and identify potentially interesting sets of associations. In this paper, we describe the application of automated discovery systems of relationships to astronomical data sets, focusing on an evolutionary programming technique and an information-theory technique. We demonstrate their use with classical astronomical relationships - the Hertzsprung-Russell diagram and the Fundamental Plane of elliptical galaxies. We also show how they work with the issue of binary classification which is relevant to the next generation of large synoptic sky surveys, such as the Large Synoptic Survey Telescope (LSST). We find that comparable results to more familiar techniques, such as decision trees, are achievable. Finally, we consider the reality of the relationships discovered and how this can be used for feature selection and extraction.

  14. Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

    Zhong, Jian-Jiang; Xiao, Jian-Hui

    Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

  15. Semantic based cluster content discovery in description first clustering algorithm

    Khan, M.W.; Asif, H.M.S.

    2017-01-01

    In the field of data analytics grouping of like documents in textual data is a serious problem. A lot of work has been done in this field and many algorithms have purposed. One of them is a category of algorithms which firstly group the documents on the basis of similarity and then assign the meaningful labels to those groups. Description first clustering algorithm belong to the category in which the meaningful description is deduced first and then relevant documents are assigned to that description. LINGO (Label Induction Grouping Algorithm) is the algorithm of description first clustering category which is used for the automatic grouping of documents obtained from search results. It uses LSI (Latent Semantic Indexing); an IR (Information Retrieval) technique for induction of meaningful labels for clusters and VSM (Vector Space Model) for cluster content discovery. In this paper we present the LINGO while it is using LSI during cluster label induction and cluster content discovery phase. Finally, we compare results obtained from the said algorithm while it uses VSM and Latent semantic analysis during cluster content discovery phase. (author)

  16. Venomics-Accelerated Cone Snail Venom Peptide Discovery

    Himaya, S. W. A.

    2018-01-01

    Cone snail venoms are considered a treasure trove of bioactive peptides. Despite over 800 species of cone snails being known, each producing over 1000 venom peptides, only about 150 unique venom peptides are structurally and functionally characterized. To overcome the limitations of the traditional low-throughput bio-discovery approaches, multi-omics systems approaches have been introduced to accelerate venom peptide discovery and characterisation. This “venomic” approach is starting to unravel the full complexity of cone snail venoms and to provide new insights into their biology and evolution. The main challenge for venomics is the effective integration of transcriptomics, proteomics, and pharmacological data and the efficient analysis of big datasets. Novel database search tools and visualisation techniques are now being introduced that facilitate data exploration, with ongoing advances in related omics fields being expected to further enhance venomics studies. Despite these challenges and future opportunities, cone snail venomics has already exponentially expanded the number of novel venom peptide sequences identified from the species investigated, although most novel conotoxins remain to be pharmacologically characterised. Therefore, efficient high-throughput peptide production systems and/or banks of miniaturized discovery assays are required to overcome this bottleneck and thus enhance cone snail venom bioprospecting and accelerate the identification of novel drug leads. PMID:29522462

  17. Venomics-Accelerated Cone Snail Venom Peptide Discovery

    S. W. A. Himaya

    2018-03-01

    Full Text Available Cone snail venoms are considered a treasure trove of bioactive peptides. Despite over 800 species of cone snails being known, each producing over 1000 venom peptides, only about 150 unique venom peptides are structurally and functionally characterized. To overcome the limitations of the traditional low-throughput bio-discovery approaches, multi-omics systems approaches have been introduced to accelerate venom peptide discovery and characterisation. This “venomic” approach is starting to unravel the full complexity of cone snail venoms and to provide new insights into their biology and evolution. The main challenge for venomics is the effective integration of transcriptomics, proteomics, and pharmacological data and the efficient analysis of big datasets. Novel database search tools and visualisation techniques are now being introduced that facilitate data exploration, with ongoing advances in related omics fields being expected to further enhance venomics studies. Despite these challenges and future opportunities, cone snail venomics has already exponentially expanded the number of novel venom peptide sequences identified from the species investigated, although most novel conotoxins remain to be pharmacologically characterised. Therefore, efficient high-throughput peptide production systems and/or banks of miniaturized discovery assays are required to overcome this bottleneck and thus enhance cone snail venom bioprospecting and accelerate the identification of novel drug leads.

  18. Functional principles of registry-based service discovery

    Sundramoorthy, V.; Tan, C.; Hartel, P.H.; Hartog, den J.I.; Scholten, J.

    2005-01-01

    As Service Discovery Protocols (SDP) are becoming increasingly important for ubiquitous computing, they must behave according to predefined principles. We present the functional Principles of Service Discovery for robust, registry-based service discovery. A methodology to guarantee adherence to

  19. Let's "Downscale" Linked Data

    Gueret, C.D.M.; de Boer, V.; Schlobach, K.S.

    2014-01-01

    Open data policies and linked data publication are powerful tools for increasing transparency, participatory governance, and accountability. The linked data community proudly emphasizes the economic and societal impact such technology shows. But a closer look proves that the design and deployment of

  20. Let's "Downscale" Linked Data

    Gueret, Christophe; de Boer, Victor; Schlobach, Stefan

    2014-01-01

    Open data policies and linked data publication are powerful tools for increasing transparency, participatory governance, and accountability. A closer look at linked data technologies, however, proves that their design and deployment exclude the majority of the world’s population. It will take small

  1. Weierstrass polynomials for links

    Hansen, Vagn Lundsgaard

    1997-01-01

    There is a natural way of identifying links in3-space with polynomial covering spaces over thecircle. Thereby any link in 3-space can be definedby a Weierstrass polynomial over the circle. Theequivalence relation for covering spaces over thecircle is, however, completely different from...

  2. A knowledge discovery in databases approach for industrial microgrid planning

    Gamarra, Carlos; Guerrero, Josep M.; Montero, Eduardo

    2016-01-01

    The progressive application of Information and Communication Technologies to industrial processes has increased the amount of data gathered by manufacturing companies during last decades. Nowadays some standardized management systems, such as ISO 50.001 and ISO 14.001, exploit these data in order...... sustainable and proactive microgrid which allows identifying, designing and developing energy efficiency strategies at supply, management and energy use levels. In this context, the expansion of Internet of Things and Knowledge Discovery in Databases techniques will drive changes in current microgrid planning...

  3. Circuits and electronics hands-on learning with analog discovery

    Okyere Attia, John

    2018-01-01

    The book provides instructions on building circuits on breadboards, connecting the Analog Discovery wires to the circuit under test, and making electrical measurements. Various measurement techniques are described and used in this book, including: impedance measurements, complex power measurements, frequency response measurements, power spectrum measurements, current versus voltage characteristic measurements of diodes, bipolar junction transistors, and Mosfets. The book includes end-of-chapter problems for additional exercises geared towards hands-on learning, experimentation, comparisons between measured results and those obtained from theoretical calculations.

  4. Native Mass Spectrometry in Fragment-Based Drug Discovery.

    Pedro, Liliana; Quinn, Ronald J

    2016-07-28

    The advent of native mass spectrometry (MS) in 1990 led to the development of new mass spectrometry instrumentation and methodologies for the analysis of noncovalent protein-ligand complexes. Native MS has matured to become a fast, simple, highly sensitive and automatable technique with well-established utility for fragment-based drug discovery (FBDD). Native MS has the capability to directly detect weak ligand binding to proteins, to determine stoichiometry, relative or absolute binding affinities and specificities. Native MS can be used to delineate ligand-binding sites, to elucidate mechanisms of cooperativity and to study the thermodynamics of binding. This review highlights key attributes of native MS for FBDD campaigns.

  5. Knowledge discovery from structured mammography reports using inductive logic programming.

    Burnside, Elizabeth S; Davis, Jesse; Costa, Victor Santos; Dutra, Inês de Castro; Kahn, Charles E; Fine, Jason; Page, David

    2005-01-01

    The development of large mammography databases provides an opportunity for knowledge discovery and data mining techniques to recognize patterns not previously appreciated. Using a database from a breast imaging practice containing patient risk factors, imaging findings, and biopsy results, we tested whether inductive logic programming (ILP) could discover interesting hypotheses that could subsequently be tested and validated. The ILP algorithm discovered two hypotheses from the data that were 1) judged as interesting by a subspecialty trained mammographer and 2) validated by analysis of the data itself.

  6. History of the discovery and clinical introduction of chlorpromazine.

    López-Muñoz, Francisco; Alamo, Cecilio; Cuenca, Eduardo; Shen, Winston W; Clervoy, Patrick; Rubio, Gabriel

    2005-01-01

    The historical process of discovery and clinical introduction of chlorpromazine, one of the greatest advances of 20th century medicine and history of psychiatry, is analyzed. In this review, we have studied the original works of pioneers in the discovery and clinical use of chlorpromazine, as well as the contributions of prestigious researchers (historians, pharmacologists, psychiatrists, etc.) about this topic. The discovery of phenothiazines, the first family of antipsychotic agents has its origin in the development of German dye industry, at the end of the 19th century (Graebe, Liebermann, Bernthsen). Up to 1940 they were employed as antiseptics, antihelminthics and antimalarials (Ehrlich, Schulemann, Gilman). Finally, in the context of research on antihistaminic substances in France after World War II (Bovet, Halpern, Ducrot) the chlorpromazine was synthesized at Rhône-Poulenc Laboratories (Charpentier, Courvoisier, Koetschet) in December 1950. Its introduction in anaesthesiology, in the antishock area (lytic cocktails) and "artificial hibernation" techniques, is reviewed (Laborit), and its further psychiatric clinical introduction in 1952, with initial discrepancies between the Parisian Val-de-Grâce (Laborit, Hamon, Paraire) and Sainte-Anne (Delay, Deniker) hospital groups. The first North-American publications on chlorpromazine took place in 1954 (Lehmann, Winkelman, Bower). The introduction of chlorpromazine in the USA (SKF) was more difficult due to their strong psychoanalytic tradition. The consolidation of the neuroleptic therapy took place in 1955, thanks to a series of scientific events, which confirmed the antipsychotic efficacy of the chlorpromazine. The discovery of the antipsychotic properties of chlorpromazine in the 1950s was a fundamental event for the practice of psychiatry and for the genesis of the so-called "psychopharmacological revolution."

  7. Systems biology and biomarker discovery

    Rodland, Karin D.

    2010-12-01

    Medical practitioners have always relied on surrogate markers of inaccessible biological processes to make their diagnosis, whether it was the pallor of shock, the flush of inflammation, or the jaundice of liver failure. Obviously, the current implementation of biomarkers for disease is far more sophisticated, relying on highly reproducible, quantitative measurements of molecules that are often mechanistically associated with the disease in question, as in glycated hemoglobin for the diagnosis of diabetes [1] or the presence of cardiac troponins in the blood for confirmation of myocardial infarcts [2]. In cancer, where the initial symptoms are often subtle and the consequences of delayed diagnosis often drastic for disease management, the impetus to discover readily accessible, reliable, and accurate biomarkers for early detection is compelling. Yet despite years of intense activity, the stable of clinically validated, cost-effective biomarkers for early detection of cancer is pathetically small and still dominated by a handful of markers (CA-125, CEA, PSA) first discovered decades ago. It is time, one could argue, for a fresh approach to the discovery and validation of disease biomarkers, one that takes full advantage of the revolution in genomic technologies and in the development of computational tools for the analysis of large complex datasets. This issue of Disease Markers is dedicated to one such new approach, loosely termed the 'Systems Biology of Biomarkers'. What sets the Systems Biology approach apart from other, more traditional approaches, is both the types of data used, and the tools used for data analysis - and both reflect the revolution in high throughput analytical methods and high throughput computing that has characterized the start of the twenty first century.

  8. Biomarkers: in medicine, drug discovery, and environmental health

    Vaidya, Vishal S; Bonventre, Joseph V

    2010-01-01

    ... Identification Using Mass Spectrometry Sample Preparation Protein Quantitation Examples of Biomarker Discovery and Evaluation Challenges in Proteomic Biomarker Discovery The Road Forward: Targeted ...

  9. Physics aids new medical techniques

    CERN. Geneva

    2001-01-01

    Since the discovery of X-rays, fundamental physics has been a source of ideas for radiography and medical imaging. A new imaging method firmly rooted in particle physics was chosen by Time magazine as one of its "Inventions of the Year 2000". The award-winning invention in the medical science category was a scanner that combined the advantages of computer tomography with positron emission tomography. The use of these techniques, which depend on detecting and analysing electromagnetic radiation (X-rays or gamma rays respectively), show that detection techniques from particle physics have made, and continue to make, essential contributions to medical science. (0 refs).

  10. Energy Reduction Multipath Routing Protocol for MANET Using Recoil Technique

    Rakesh Kumar Sahu

    2018-04-01

    Full Text Available In Mobile Ad-hoc networks (MANET, power conservation and utilization is an acute problem and has received significant attention from academics and industry in recent years. Nodes in MANET function on battery power, which is a rare and limited energy resource. Hence, its conservation and utilization should be done judiciously for the effective functioning of the network. In this paper, a novel protocol namely Energy Reduction Multipath Routing Protocol for MANET using Recoil Technique (AOMDV-ER is proposed, which conserves the energy along with optimal network lifetime, routing overhead, packet delivery ratio and throughput. It performs better than any other AODV based algorithms, as in AOMDV-ER the nodes transmit packets to their destination smartly by using a varying recoil off time technique based on their geographical location. This concept reduces the number of transmissions, which results in the improvement of network lifetime. In addition, the local level route maintenance reduces the additional routing overhead. Lastly, the prediction based link lifetime of each node is estimated which helps in reducing the packet loss in the network. This protocol has three subparts: an optimal route discovery algorithm amalgamation with the residual energy and distance mechanism; a coordinated recoiled nodes algorithm which eliminates the number of transmissions in order to reduces the data redundancy, traffic redundant, routing overhead, end to end delay and enhance the network lifetime; and a last link reckoning and route maintenance algorithm to improve the packet delivery ratio and link stability in the network. The experimental results show that the AOMDV-ER protocol save at least 16% energy consumption, 12% reduction in routing overhead, significant achievement in network lifetime and packet delivery ratio than Ad hoc on demand multipath distance vector routing protocol (AOMDV, Ad hoc on demand multipath distance vector routing protocol life

  11. Single well techniques

    Drost, W.

    1983-01-01

    The single well technique method includes measurement of parameters of groundwater flow in saturated rock. For determination of filtration velocity the dilution of radioactive tracer is measured, for direction logging the collimeter is rotated in the probe linked with the compass. The limiting factor for measurement of high filtration velocities is the occurrence of turbulent flow. The single well technique is used in civil engineering projects, water works and subsurface drainage of liquid waste from disposal sites. The radioactive tracer method for logging the vertical fluid movement in bore-holes is broadly used in groundwater survey and exploitation. (author)

  12. Effective Online Group Discovery in Trajectory Databases

    Li, Xiaohui; Ceikute, Vaida; Jensen, Christian S.

    2013-01-01

    GPS-enabled devices are pervasive nowadays. Finding movement patterns in trajectory data stream is gaining in importance. We propose a group discovery framework that aims to efficiently support the online discovery of moving objects that travel together. The framework adopts a sampling-independen......GPS-enabled devices are pervasive nowadays. Finding movement patterns in trajectory data stream is gaining in importance. We propose a group discovery framework that aims to efficiently support the online discovery of moving objects that travel together. The framework adopts a sampling......-independent approach that makes no assumptions about when positions are sampled, gives no special importance to sampling points, and naturally supports the use of approximate trajectories. The framework's algorithms exploit state-of-the-art, density-based clustering (DBScan) to identify groups. The groups are scored...

  13. Drug discovery and developments in developing countries ...

    the major burden being in developing countries. Many of ... The driving force for drug discovery and development by pharmaceutical firms ... world and particularly in the third world countries ..... GFHR (2000) Global Forum for Health Research:.

  14. Story of Superconductivity: A Serendipitous Discovery

    , offered a glimmerof hope to make this dream possible. It was a discoverytotally unexpected at that time, and we owe this discovery tothe painstaking andmethodical investigations of Onnes – firstto produce very low temperatures, and then ...

  15. Discovery of nuclear fission in Berlin 1938

    Hilscher, D.

    1989-01-01

    The story of the discovery of nuclear fission, one of the most exciting stories of how a scientific puzzle was finally solved and how the scientists involved were blind to many obvious indications, is described. (author). 29 refs

  16. Discovery of two new gravitation lens systems

    Guertler, J.

    1988-01-01

    The discovery of new quasar and radio galaxy double images produced by the gravitation lens effect is reported. The light deflecting galaxies acting as gravitational lenses could be made visible by means of image processing procedures

  17. Queen's discovery lauded by top scientific journal

    McGrady, S

    2002-01-01

    A scientific breakthrough at Queen's University's Sudbury Neutrino Observatory has received major international recognition. The journal Science ranked the discovery that cracked the "neutrino problem" second, in the journal's top 10 scientific achievements of 2002 (1/2 page).

  18. Price discovery in European natural gas markets

    Schultz, Emma; Swieringa, John

    2013-01-01

    We provide the first high-frequency investigation of price discovery within the physical and financial layers of Europe's natural gas markets. Testing not only looks at short-term return dynamics, but also considers each security's contribution to price equilibrium in the longer-term. Results show that UK natural gas futures traded on the Intercontinental Exchange display greater price discovery than physical trading at various hubs throughout Europe. - Highlights: • We use intraday data to gauge price discovery in European natural gas markets. • We explore short and long-term dynamics in physical and financial market layers. • Results show ICE's UK natural gas futures are the main venue for price discovery

  19. Discovery of Intrinsic Primitives on Triangle Meshes

    Solomon, Justin; Ben-Chen, Mirela; Butscher, Adrian; Guibas, Leonidas

    2011-01-01

    The discovery of meaningful parts of a shape is required for many geometry processing applications, such as parameterization, shape correspondence, and animation. It is natural to consider primitives such as spheres, cylinders and cones

  20. The Uniframe .Net Web Service Discovery Service

    Berbeco, Robert W

    2003-01-01

    ...) and registered with Internet Information Server (IIS), and can be applied in numerous fashions This project uses the NET capabilities to create a distributed discovery service (called as UNWSDS...

  1. MENINGKATKAN PEMAHAMAN MAHASISWA PADA MATA KULIAH KONSEP DASAR IPA MENGGUNAKAN MODEL PEMBELAJARAN CBSA DENGAN PENDEKATAN DISCOVERY

    Subuh Anggoro

    2010-03-01

    Full Text Available This research is aimed at finding out whether students’ active learning with discovery approach could improve the students’ understanding of basic science subject. The research used survey method. The population of this research was students who took the subject of Konsep Dasar IPA (the Basic Concept of Science out of which one class was taken as sample. The data was then analyzed with descriptive technique with the help of graph. The result showed that 72% did not have sufficient understanding about the topic of energy and its transformation which was delivered without the help of learning aid and discussion. After learning aid was and discussion was facilitated by the lecturer, all the subjects of this research expressed their better improved understanding. Discovery method with experiment and discussion is crucial in helping students understand the basic concept of science. Key words: understanding, basic concept of science learning, students’ active learning, discovery technique.

  2. Dismantling techniques

    Wiese, E.

    1998-01-01

    Most of the dismantling techniques used in a Decontamination and Dismantlement (D and D) project are taken from conventional demolition practices. Some modifications to the techniques are made to limit exposure to the workers or to lessen the spread of contamination to the work area. When working on a D and D project, it is best to keep the dismantling techniques and tools as simple as possible. The workers will be more efficient and safer using techniques that are familiar to them. Prior experience with the technique or use of mock-ups is the best way to keep workers safe and to keep the project on schedule

  3. Dismantling techniques

    Wiese, E.

    1998-03-13

    Most of the dismantling techniques used in a Decontamination and Dismantlement (D and D) project are taken from conventional demolition practices. Some modifications to the techniques are made to limit exposure to the workers or to lessen the spread of contamination to the work area. When working on a D and D project, it is best to keep the dismantling techniques and tools as simple as possible. The workers will be more efficient and safer using techniques that are familiar to them. Prior experience with the technique or use of mock-ups is the best way to keep workers safe and to keep the project on schedule.

  4. The discovery of the structure of DNA

    Squires, G. L.

    2003-04-01

    On 25 April 1953, Nature published a letter by Francis Crick and James Watson, at the Cavendish Laboratory, Cambridge, proposing a structure for DNA. This letter marked the beginning of a revolution in biology. Besides Crick and Watson, two other scientists, Rosalind Franklin and Maurice Wilkins, played key roles in the discovery. After sketching the early careers of the four scientists, the present article gives an account of the physics and chemistry involved in the discovery, and the events leading up to it.

  5. Fission and the discovery of isotopes

    Thoennessen, M.

    2014-01-01

    The discovery of new isotopes requires new developments in accelerator and detector technology. The new RI Beam Factory at RIKEN and the future projects FAIR at GSI and FRIB at MSU promise to expand the nuclear horizon even further. In the talk a short history of the role that fission played in the discovery of isotopes will be presented and future perspectives will be discussed

  6. The Gozo discovery bus : a successful experiment

    Vella, Maryrose

    2008-01-01

    The introduction of a tourist discovery bus in Gozo came about as a result of an EU Project which is part of the Interreg III B Archimed programmes in which the Islands and Small States Institute of the University of Malta participated. Other countries participating in this programme besides Malta, represented by the Islands and Small States Institute, are Italy, Cyprus and Greece. The discovery bus service was aimed at encouraging more tourists to come to Gozo and enabling them to visit stra...

  7. Discovery of the Higgs boson and beyond

    Godbole, Rohini

    2014-01-01

    This talk is about the Higgs mechanism, the theoretical discovery of which, was awarded the 2013 Nobel Prize. It also discusses the discovery of the Higgs boson at the large hadron collider which provided the experimental proof that made the Nobel prize possible. It covers the implications of these for the quest of unravelling the fundamental laws of nature which seem to govern both, the behavior of the ultra small (subatomic particles) and the ultra large (the cosmos)

  8. Studying Scientific Discovery by Computer Simulation.

    1983-03-30

    Mendel’s laws of inheritance, the law of Gay- Lussac for gaseous reactions, tile law of Dulong and Petit, the derivation of atomic weights by Avogadro...neceseary mid identify by block number) scientific discovery -ittri sic properties physical laws extensive terms data-driven heuristics intensive...terms theory-driven heuristics conservation laws 20. ABSTRACT (Continue on revere. side It necessary and identify by block number) Scientific discovery

  9. Applying genetics in inflammatory disease drug discovery

    Folkersen, Lasse; Biswas, Shameek; Frederiksen, Klaus Stensgaard

    2015-01-01

    , with several notable exceptions, the journey from a small-effect genetic variant to a functional drug has proven arduous, and few examples of actual contributions to drug discovery exist. Here, we discuss novel approaches of overcoming this hurdle by using instead public genetics resources as a pragmatic guide...... alongside existing drug discovery methods. Our aim is to evaluate human genetic confidence as a rationale for drug target selection....

  10. Roentgen and the discovery of X rays

    Gueret, Ph.

    1998-01-01

    In 1901, the first Nobel price of physics was attributed to Roentgen for his discovery of X rays. This paper recalls through the career of this physicist and research worker, the different steps that led him to this discovery. This paper tries also to solve the 'Roentgen mystery', i.e. the reasons that led him to stop his research work just after this exploit. (J.S.)

  11. Developing integrated crop knowledge networks to advance candidate gene discovery.

    Hassani-Pak, Keywan; Castellote, Martin; Esch, Maria; Hindle, Matthew; Lysenko, Artem; Taubert, Jan; Rawlings, Christopher

    2016-12-01

    The chances of raising crop productivity to enhance global food security would be greatly improved if we had a complete understanding of all the biological mechanisms that underpinned traits such as crop yield, disease resistance or nutrient and water use efficiency. With more crop genomes emerging all the time, we are nearer having the basic information, at the gene-level, to begin assembling crop gene catalogues and using data from other plant species to understand how the genes function and how their interactions govern crop development and physiology. Unfortunately, the task of creating such a complete knowledge base of gene functions, interaction networks and trait biology is technically challenging because the relevant data are dispersed in myriad databases in a variety of data formats with variable quality and coverage. In this paper we present a general approach for building genome-scale knowledge networks that provide a unified representation of heterogeneous but interconnected datasets to enable effective knowledge mining and gene discovery. We describe the datasets and outline the methods, workflows and tools that we have developed for creating and visualising these networks for the major crop species, wheat and barley. We present the global characteristics of such knowledge networks and with an example linking a seed size phenotype to a barley WRKY transcription factor orthologous to TTG2 from Arabidopsis, we illustrate the value of integrated data in biological knowledge discovery. The software we have developed (www.ondex.org) and the knowledge resources (http://knetminer.rothamsted.ac.uk) we have created are all open-source and provide a first step towards systematic and evidence-based gene discovery in order to facilitate crop improvement.

  12. Link to paper

    U.S. Environmental Protection Agency — Link to the paper. This dataset is associated with the following publication: Naile, J., A.W. Garrison, J. Avants, and J. Washington. Isomers/enantiomers of...

  13. The Missing Link

    Schultz, Laura Luise

    2014-01-01

    Paper presented at A Valentine to Gertrude Stein. The Reception of Gertrude Stein in the Arts and Humanities, held at the University of Copenhagen 8. - 10. May 2014, in collaboration with the universities of Ghent and Linköping......Paper presented at A Valentine to Gertrude Stein. The Reception of Gertrude Stein in the Arts and Humanities, held at the University of Copenhagen 8. - 10. May 2014, in collaboration with the universities of Ghent and Linköping...

  14. Shuttle Discovery Landing at Edwards

    1989-01-01

    The STS-29 Space Shuttle Discovery mission lands at NASA's then Ames-Dryden Flight Research Facility, Edwards AFB, California, early Saturday morning, 18 March 1989. Touchdown was at 6:35:49 a.m. PST and wheel stop was at 6:36:40 a.m. on runway 22. Controllers chose the concrete runway for the landing in order to make tests of braking and nosewheel steering. The STS-29 mission was very successful, completing the launch of a Tracking and Data Relay communications satellite, as well as a range of scientific experiments. Discovery's five-man crew was led by Commander Michael L. Coats, and included pilot John E. Blaha and mission specialists James P. Bagian, Robert C. Springer, and James F. Buchli. Space Shuttles are the main element of America's Space Transportation System and are used for space research and other space applications. The shuttles are the first vehicles capable of being launched into space and returning to Earth on a routine basis. Space Shuttles are used as orbiting laboratories in which scientists and mission specialists conduct a wide variety of scientific experiments. Crews aboard shuttles place satellites in orbit, rendezvous with satellites to carry out repair missions and return them to space, and retrieve satellites and return them to Earth for refurbishment and reuse. Space Shuttles are true aerospace vehicles. They leave Earth and its atmosphere under rocket power provided by three liquid-propellant main engines with two solid-propellant boosters attached plus an external liquid-fuel tank. After their orbital missions, they streak back through the atmosphere and land like airplanes. The returning shuttles, however, land like gliders, without power and on runways. Other rockets can place heavy payloads into orbit, but, they can only be used once. Space Shuttles are designed to be continually reused. When Space Shuttles are used to transport complete scientific laboratories into space, the laboratories remain inside the payload bay throughout

  15. Fragment-based approaches to the discovery of kinase inhibitors.

    Mortenson, Paul N; Berdini, Valerio; O'Reilly, Marc

    2014-01-01

    Protein kinases are one of the most important families of drug targets, and aberrant kinase activity has been linked to a large number of disease areas. Although eminently targetable using small molecules, kinases present a number of challenges as drug targets, not least obtaining selectivity across such a large and relatively closely related target family. Fragment-based drug discovery involves screening simple, low-molecular weight compounds to generate initial hits against a target. These hits are then optimized to more potent compounds via medicinal chemistry, usually facilitated by structural biology. Here, we will present a number of recent examples of fragment-based approaches to the discovery of kinase inhibitors, detailing the construction of fragment-screening libraries, the identification and validation of fragment hits, and their optimization into potent and selective lead compounds. The advantages of fragment-based methodologies will be discussed, along with some of the challenges associated with using this route. Finally, we will present a number of key lessons derived both from our own experience running fragment screens against kinases and from a large number of published studies.

  16. Reuse-oriented common structure discovery in assembly models

    Wang, Pan; Zhang Jie; Li, Yuan; Yu, Jian Feng

    2017-01-01

    Discovering the common structures in assembly models provides designers with the commonalities that carry significant design knowledge across multiple products, which helps to improve design efficiency and accelerate the design process. In this paper, a discovery method has been developed to obtain the common structure in assembly models. First, this work proposes a graph descriptor that captures both the geometrical and topological information of the assembly model, in which shape vectors and link vectors quantitatively describe the part models and mating relationships, respectively. Then, a clustering step is introduced into the discovery, which clusters the similar parts by comparing the similarities between them. In addition, some rules are also provided to filter the frequent subgraphs in order to obtain the expected results. Compared with the existing method, the proposed approach could overcome the disadvantages by providing an independent description of the part model and taking into consideration the similar parts in assemblies, which leads to a more reasonable result. Finally, some experiments have been carried out and the experimental results demonstrate the effectiveness of the proposed approach

  17. Reuse-oriented common structure discovery in assembly models

    Wang, Pan; Zhang Jie; Li, Yuan; Yu, Jian Feng [The Ministry of Education Key Lab of Contemporary Design and Integrated Manufacturing Technology, Northwestern Polytechnical University, Xian (China)

    2017-01-15

    Discovering the common structures in assembly models provides designers with the commonalities that carry significant design knowledge across multiple products, which helps to improve design efficiency and accelerate the design process. In this paper, a discovery method has been developed to obtain the common structure in assembly models. First, this work proposes a graph descriptor that captures both the geometrical and topological information of the assembly model, in which shape vectors and link vectors quantitatively describe the part models and mating relationships, respectively. Then, a clustering step is introduced into the discovery, which clusters the similar parts by comparing the similarities between them. In addition, some rules are also provided to filter the frequent subgraphs in order to obtain the expected results. Compared with the existing method, the proposed approach could overcome the disadvantages by providing an independent description of the part model and taking into consideration the similar parts in assemblies, which leads to a more reasonable result. Finally, some experiments have been carried out and the experimental results demonstrate the effectiveness of the proposed approach.

  18. The Sterile Insect Technique

    Kiragu, J.

    2006-01-01

    Insect pests have caused an increasing problem in agriculture and human health through crop losses and disease transmission to man and livestock. Intervention to ensure food security and human health has relied on Integrated Pest Management (IPM) strategies to keep the pests population below economic injury levels. IPM integrate a variety of methods, but there has been over-reliance on chemical control following the discovery of insecticidal properties of DDT. It is now realized that, maintaining pest populations at controlled levels is unsustainable and eradication options is now being considered. Although the Sterile Insect Technique(SIT) could be used for insect suppression, it is gaining favour in the elimination (eradication) of the target pest population through Areawide-based IPM (Author)

  19. Discovery of a nucleocytoplasmic O-mannose glycoproteome in yeast

    Halim, Adnan; Larsen, Ida Signe Bohse; Neubert, Patrick

    2015-01-01

    developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. Here, we applied...... the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. Such O-Man glycoproteins were not found in our analysis of human cell lines....... However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. The discovery...

  20. Encouraging data citation and discovery with the Data Citation Index.

    Force, Megan M; Robinson, Nigel J

    2014-10-01

    An overview of the Data Citation Index is provided. Thomson Reuters developed this resource in response to a stated desire among members of the research community for increased attribution of non-traditional scholarly output. Launched in October of 2012 on the Web of science research platform, its aims include linking published research articles to their underlying data sets and tracking the citation of the data, as well as encouraging bibliographic citation of data. Cross-disciplinary search capabilities in the Index enable new possibilities for data discovery and synthesis. Data repositories are evaluated with respect to various selection criteria, with particular attention to their relevance to scientific and scholarly research. Index content reflects current data deposition practices. As data citation standards and practices continue to move toward widespread formalization and adoption, the initiative seeks to address issues of data citation, reuse, and author credit in a developing climate.

  1. Space technology in the discovery and development of mineral and energy resources

    Lowman, P. D.

    1977-01-01

    Space technology, applied to the discovery and extraction of mineral and energy resources, is summarized. Orbital remote sensing for geological purposes has been widely applied through the use of LANDSAT satellites. These techniques also have been of value for protection against environmental hazards and for a better understanding of crustal structure.

  2. Service discovery from observed behavior while guaranteeing deadlock freedom in collaborations

    Müller, R.; Stahl, C.; Aalst, van der W.M.P.; Westergaard, M.

    2013-01-01

    Process discovery techniques can be used to derive a process model from observed example behavior (i.e., an event log). As the observed behavior is inherently incomplete and models may serve different purposes, four competing quality dimensions --fi tness, precision, simplicity, and generalization--

  3. Service discovery from observed behavior while guaranteeing deadlock freedom in collaborations

    Müller, R.; Stahl, C.; Aalst, van der W.M.P.; Westergaard, M.; Basu, S.; Pautasso, C.; Zhang, L.; Fu, X.

    2013-01-01

    Process discovery techniques can be used to derive a process model from observed example behavior (i.e., an event log). As the observed behavior is inherently incomplete and models may serve different purposes, four competing quality dimensions—fitness, precision, simplicity, and generalization—have

  4. Teaching Tip: Using Rapid Game Prototyping for Exploring Requirements Discovery and Modeling

    Dalal, Nikunj

    2012-01-01

    We describe the use of rapid game prototyping as a pedagogic technique to experientially explore and learn requirements discovery, modeling, and specification in systems analysis and design courses. Students have a natural interest in gaming that transcends age, gender, and background. Rapid digital game creation is used to build computer games…

  5. Next-Generation Sequencing Approaches in Genome-Wide Discovery of Single Nucleotide Polymorphism Markers Associated with Pungency and Disease Resistance in Pepper.

    Manivannan, Abinaya; Kim, Jin-Hee; Yang, Eun-Young; Ahn, Yul-Kyun; Lee, Eun-Su; Choi, Sena; Kim, Do-Sun

    2018-01-01

    Pepper is an economically important horticultural plant that has been widely used for its pungency and spicy taste in worldwide cuisines. Therefore, the domestication of pepper has been carried out since antiquity. Owing to meet the growing demand for pepper with high quality, organoleptic property, nutraceutical contents, and disease tolerance, genomics assisted breeding techniques can be incorporated to develop novel pepper varieties with desired traits. The application of next-generation sequencing (NGS) approaches has reformed the plant breeding technology especially in the area of molecular marker assisted breeding. The availability of genomic information aids in the deeper understanding of several molecular mechanisms behind the vital physiological processes. In addition, the NGS methods facilitate the genome-wide discovery of DNA based markers linked to key genes involved in important biological phenomenon. Among the molecular markers, single nucleotide polymorphism (SNP) indulges various benefits in comparison with other existing DNA based markers. The present review concentrates on the impact of NGS approaches in the discovery of useful SNP markers associated with pungency and disease resistance in pepper. The information provided in the current endeavor can be utilized for the betterment of pepper breeding in future.

  6. Next-Generation Sequencing Approaches in Genome-Wide Discovery of Single Nucleotide Polymorphism Markers Associated with Pungency and Disease Resistance in Pepper

    Abinaya Manivannan

    2018-01-01

    Full Text Available Pepper is an economically important horticultural plant that has been widely used for its pungency and spicy taste in worldwide cuisines. Therefore, the domestication of pepper has been carried out since antiquity. Owing to meet the growing demand for pepper with high quality, organoleptic property, nutraceutical contents, and disease tolerance, genomics assisted breeding techniques can be incorporated to develop novel pepper varieties with desired traits. The application of next-generation sequencing (NGS approaches has reformed the plant breeding technology especially in the area of molecular marker assisted breeding. The availability of genomic information aids in the deeper understanding of several molecular mechanisms behind the vital physiological processes. In addition, the NGS methods facilitate the genome-wide discovery of DNA based markers linked to key genes involved in important biological phenomenon. Among the molecular markers, single nucleotide polymorphism (SNP indulges various benefits in comparison with other existing DNA based markers. The present review concentrates on the impact of NGS approaches in the discovery of useful SNP markers associated with pungency and disease resistance in pepper. The information provided in the current endeavor can be utilized for the betterment of pepper breeding in future.

  7. Translation Techniques

    Marcia Pinheiro

    2015-01-01

    In this paper, we discuss three translation techniques: literal, cultural, and artistic. Literal translation is a well-known technique, which means that it is quite easy to find sources on the topic. Cultural and artistic translation may be new terms. Whilst cultural translation focuses on matching contexts, artistic translation focuses on matching reactions. Because literal translation matches only words, it is not hard to find situations in which we should not use this technique.  Because a...

  8. Chronicling a journey of discovery

    Panos Charitos

    2013-01-01

    This year ALICE celebrates 20 years of exploration of the world of strong interactions and the Quark Gluon Plasma. To mark the anniversary, the collaboration has created a timeline that chronicles the experiment’s history from 1993, when the original letter of intent was submitted, to 2013, when the first proton-lead run took place.   The ALICE timeline examines various key aspects of the experiment’s history, including the connection between ALICE and other heavy ion experiments. Over the years, the experiment has adapted along with developments on heavy ion physics. ALICE has added several new components to the detector following new experimental findings. The timeline also links the experiment’s history with the theoretical advancements in the field of QCD and the growing understanding of strong interactions. But let’s not forget the human element of the experiment’s history. It has taken a lot of hard work to build the d...

  9. Experimental discovery of nodal chains

    Yan, Qinghui; Liu, Rongjuan; Yan, Zhongbo; Liu, Boyuan; Chen, Hongsheng; Wang, Zhong; Lu, Ling

    2018-05-01

    Three-dimensional Weyl and Dirac nodal points1 have attracted widespread interest across multiple disciplines and in many platforms but allow for few structural variations. In contrast, nodal lines2-4 can have numerous topological configurations in momentum space, forming nodal rings5-9, nodal chains10-15, nodal links16-20 and nodal knots21,22. However, nodal lines are much less explored because of the lack of an ideal experimental realization23-25. For example, in condensed-matter systems, nodal lines are often fragile to spin-orbit coupling, located away from the Fermi level, coexist with energy-degenerate trivial bands or have a degeneracy line that disperses strongly in energy. Here, overcoming all these difficulties, we theoretically predict and experimentally observe nodal chains in a metallic-mesh photonic crystal having frequency-isolated linear band-touching rings chained across the entire Brillouin zone. These nodal chains are protected by mirror symmetry and have a frequency variation of less than 1%. We use angle-resolved transmission measurements to probe the projected bulk dispersion and perform Fourier-transformed field scans to map out the dispersion of the drumhead surface state. Our results establish an ideal nodal-line material for further study of topological line degeneracies with non-trivial connectivity and consequent wave dynamics that are richer than those in Weyl and Dirac materials.

  10. Reporting Astronomical Discoveries: Past, Now, and Future

    Yamaoka, Hitoshi; Green, Daniel W. E.; Samus, Nikolai N.; West, Richard

    2015-08-01

    Many new astronomical objects have been discovered over the years by amateur astronomers, and this continues to be the case. They have traditionally reported them (as have professional astronomers) to the Central Bureau for Astronomical Telegrams (CBAT), which was established in the 19th century. This procedure has worked very well throughout the 20th century, moving under the umbrella of the newly established IAU in 1920. The discoverers have been honored by the formal announcement of their discoveries in the publications of the CBAT.In recent years, some professional research groups have established other ways of announcing their discoveries of explosive objects such as novae and supernovae; some do not now report their discoveries or spectroscopic confirmations of the transients to the CBAT, including often spectroscopic reports of objects posted to the CBAT "Transient Objects Confirmation Page" -- the highly successful TOCP webpage, which assigns official positional designations to new transients posted there by approved, registered users. This leads to a delay in formal announcements of discoveries by amateur astronomers in many cases, as well as inconsistent designations being put into use by individual groups. Amateur astronomers are feeling frustrated about this situation, and they hope that the IAU will help to settle the situation.We have proposed the new IAU commission NC-52, which will treat these phenomena in a continuation of Commission 6, through the CBAT. We hope to continuously support the reporting of the discoveries by amateur astronomers, as well as professional astronomers, who all deserve and desire proper recognition. Our strategy will maintain the firm trust between the amateur and professional astronomers, which is necessary for true collaboration. The plan is for the CBAT to work with collaborators to assure that discoveries posted on the TOCP are promptly designated and announced by the CBAT, even when confirmations are made elsewhere

  11. Clinical Perspective Linking theory and technique in a systems ...

    The paper describes a programme for disadvantaged children with learning problems (due to factors other than cognitive deficits), at the University of Cape Town (UCT) Child Guidance Clinic, developed in the absence of subsidised services for children in need of remediation of scholastic skills. In collaboration with teacher ...

  12. 12 CFR 747.24 - Scope of document discovery.

    2010-01-01

    ... act of Congress, or the principles of common law provide. (d) Time limits. All discovery, including... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Scope of document discovery. 747.24 Section 747... of Practice and Procedure § 747.24 Scope of document discovery. (a) Limits on discovery. (1) Subject...

  13. Integration of Lead Discovery Tactics and the Evolution of the Lead Discovery Toolbox.

    Leveridge, Melanie; Chung, Chun-Wa; Gross, Jeffrey W; Phelps, Christopher B; Green, Darren

    2018-06-01

    There has been much debate around the success rates of various screening strategies to identify starting points for drug discovery. Although high-throughput target-based and phenotypic screening has been the focus of this debate, techniques such as fragment screening, virtual screening, and DNA-encoded library screening are also increasingly reported as a source of new chemical equity. Here, we provide examples in which integration of more than one screening approach has improved the campaign outcome and discuss how strengths and weaknesses of various methods can be used to build a complementary toolbox of approaches, giving researchers the greatest probability of successfully identifying leads. Among others, we highlight case studies for receptor-interacting serine/threonine-protein kinase 1 and the bromo- and extra-terminal domain family of bromodomains. In each example, the unique insight or chemistries individual approaches provided are described, emphasizing the synergy of information obtained from the various tactics employed and the particular question each tactic was employed to answer. We conclude with a short prospective discussing how screening strategies are evolving, what this screening toolbox might look like in the future, how to maximize success through integration of multiple tactics, and scenarios that drive selection of one combination of tactics over another.

  14. From the endometrium physiology to a comprehensive strategy for the discovery of ovarian cancer biomarkers

    Janos L. Tanyi; Nathalie Scholler

    2011-01-01

    The development of comprehensive strategies for biomarker discovery of gynecological cancers is needed. The unique physiology of the female genital track revolves around ovulatory cycles ending by the proteolysis of the endometrium triggered by progesterone decline during the last part of the luteal phase. Building on the known link between incessant ovulation and ovarian cancer, we hypothesize that life-long menstruations could damage neighboring organs such as fallopian tubes, ovaries and p...

  15. Fermat's Technique of Finding Areas under Curves

    Staples, Ed

    2004-01-01

    Perhaps next time teachers head towards the fundamental theorem of calculus in their classroom, they may wish to consider Fermat's technique of finding expressions for areas under curves, beautifully outlined in Boyer's History of Mathematics. Pierre de Fermat (1601-1665) developed some important results in the journey toward the discovery of the…

  16. Improving data discovery and usability through commentary and user feedback: the CHARMe project

    Alegre, R.; Blower, J. D.

    2014-12-01

    Earth science datasets are highly diverse. Users of these datasets are similarly varied, ranging from research scientists through industrial users to government decision- and policy-makers. It is very important for these users to understand the applicability of any dataset to their particular problem so that they can select the most appropriate data sources for their needs. Although data providers often provide rich supporting information in the form of metadata, typically this information does not include community usage information that can help other users judge fitness-for-purpose.The CHARMe project (http://www.charme.org.uk) is filling this gap by developing a system for sharing "commentary metadata". These are annotations that are generated and shared by the user community and include: Links between publications and datasets. The CHARMe system can record information about why a particular dataset was used (e.g. the paper may describe the dataset, it may use the dataset as a source, or it may be publishing results of a dataset assessment). These publications may appear in the peer-reviewed literature, or may be technical reports, websites or blog posts. Free-text comments supplied by the user. Provenance information, including links between datasets and descriptions of processing algorithms and sensors. External events that may affect data quality (e.g. large volcanic eruptions or El Niño events); we call these "significant events". Data quality information, e.g. system maturity indices. Commentary information can be linked to anything that can be uniquely identified (e.g. a dataset with a DOI or a persistent web address). It is also possible to associate commentary with particular subsets of datasets, for example to highlight an issue that is confined to a particular geographic region. We will demonstrate tools that show these capabilities in action, showing how users can apply commentary information during data discovery, visualization and analysis. The

  17. The linked medical data access control framework.

    Kamateri, Eleni; Kalampokis, Evangelos; Tambouris, Efthimios; Tarabanis, Konstantinos

    2014-08-01

    The integration of medical data coming from multiple sources is important in clinical research. Amongst others, it enables the discovery of appropriate subjects in patient-oriented research and the identification of innovative results in epidemiological studies. At the same time, the integration of medical data faces significant ethical and legal challenges that impose access constraints. Some of these issues can be addressed by making available aggregated instead of raw record-level data. In many cases however, there is still a need for controlling access even to the resulting aggregated data, e.g., due to data provider's policies. In this paper we present the Linked Medical Data Access Control (LiMDAC) framework that capitalizes on Linked Data technologies to enable controlling access to medical data across distributed sources with diverse access constraints. The LiMDAC framework consists of three Linked Data models, namely the LiMDAC metadata model, the LiMDAC user profile model, and the LiMDAC access policy model. It also includes an architecture that exploits these models. Based on the framework, a proof-of-concept platform is developed and its performance and functionality are evaluated by employing two usage scenarios. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Earth2Class Overview: An Innovative Program Linking Classroom Educators and Research Scientists

    Passow, M.; Iturrino, G. J.; Baggio, F. D.; Assumpcao, C. M.

    2005-12-01

    Jersey to consider challenges facing classroom teachers trying to incorporate recent research discoveries into the curriculum. Their efforts led to creating web-based resources that provide succinct statements of core concepts, essential vocabulary lists, selected labs, activities, and links to Internet sites providing scientific information that may not be incorporated into textbooks for years. The E2C web site (www.earth2class.org), has become an important resource for Earth Science educators. It provides an effective format for disseminating results of scientific research to teachers and students through a workshop section that includes an introduction, links to scientific discoveries, and suggestions for classroom applications. The educational resources section provides extensive curricular materials, including lesson plans, classroom activities, and links to state and national Science Education Standards. Overall, E2C seeks to make significant contributions to national efforts for creating networks of science researchers working with classroom teachers and teacher-trainers seeking effective methods for innovative instructional techniques, problem-solving strategies, and professional development, as well as meeting the challenges of state and national mandates.

  19. Choosing Discovery: A Literature Review on the Selection and Evaluation of Discovery Layers

    Moore, Kate B.; Greene, Courtney

    2012-01-01

    Within the next few years, traditional online public access catalogs will be replaced by more robust and interconnected discovery layers that can serve as primary public interfaces to simultaneously search many separate collections of resources. Librarians have envisioned this type of discovery tool since the 1980s, and research shows that…

  20. Current status and future prospects for enabling chemistry technology in the drug discovery process [version 1; referees: 2 approved

    Stevan W. Djuric

    2016-09-01

    Full Text Available This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of “dangerous” reagents. Also featured are advances in the “computer-assisted drug design” area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities.