WorldWideScience

Sample records for link discovery techniques

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

    OpenAIRE

    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 ...

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

    Science.gov (United States)

    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.

  3. Performance Evaluation of Frequent Subgraph Discovery Techniques

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  9. The OceanLink Project

    Science.gov (United States)

    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.

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

    CERN Document Server

    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

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

    Science.gov (United States)

    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.

  12. Enhancing Big Data Value Using Knowledge Discovery Techniques

    OpenAIRE

    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...

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

    DEFF Research Database (Denmark)

    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...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    NARCIS (Netherlands)

    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

  17. Introduction to fragment-based drug discovery.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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).

  1. A Technique Socratic Questioning-Guided Discovery

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  4. Semantic Service Discovery Techniques for the composable web

    OpenAIRE

    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...

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

    NARCIS (Netherlands)

    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

  6. Proteomic and metabolomic approaches to biomarker discovery

    CERN Document Server

    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...

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

    International Nuclear Information System (INIS)

    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)

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

    DEFF Research Database (Denmark)

    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...

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

    Indian Academy of Sciences (India)

    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 ...

  10. Measuring Journal Linking Success from a Discovery Service

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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,…

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

    Science.gov (United States)

    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.

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

    CERN Document Server

    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...

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Drugs + HIV, Learn the Link

    Medline Plus

    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 ...

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

    DEFF Research Database (Denmark)

    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...

  19. Representation Discovery using Harmonic Analysis

    CERN Document Server

    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

  20. Discovery in a World of Mashups

    Science.gov (United States)

    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.

  1. Pattern Discovery in Time-Ordered Data; TOPICAL

    International Nuclear Information System (INIS)

    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. Solution NMR Spectroscopy in Target-Based Drug Discovery.

    Science.gov (United States)

    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.

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

    NARCIS (Netherlands)

    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

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

    DEFF Research Database (Denmark)

    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...

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    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...

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

    OpenAIRE

    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.

  8. Multidimensional process discovery

    NARCIS (Netherlands)

    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

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

    Science.gov (United States)

    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. From the nucleus discovery to DWBA

    International Nuclear Information System (INIS)

    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

  11. Polonium: 110th anniversary of its discovery

    International Nuclear Information System (INIS)

    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)

  12. Computational methods in drug discovery

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  16. Deep Learning in Drug Discovery.

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    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

  18. Advances in fragment-based drug discovery platforms.

    Science.gov (United States)

    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. Data mining-aided materials discovery and optimization

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  1. Discovery – The Link to H.Pylori Bacteria

    Science.gov (United States)

    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.

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

    NARCIS (Netherlands)

    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

  3. Drugs + HIV, Learn the Link

    Medline Plus

    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 ...

  4. Sparse Mbplsr for Metabolomics Data and Biomarker Discovery

    DEFF Research Database (Denmark)

    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...

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

    DEFF Research Database (Denmark)

    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....

  6. User-guided discovery of declarative process models

    NARCIS (Netherlands)

    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.

  7. Discovery of SM Higgs Boson in ATLAS Experiment

    Indian Academy of Sciences (India)

    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:

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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.

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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.

  13. Pharmacological screening technologies for venom peptide discovery.

    Science.gov (United States)

    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.

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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…

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

    CERN Document Server

    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

  17. Predictors of timing of pregnancy discovery.

    Science.gov (United States)

    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.

  18. The centenary of discovery of radium

    International Nuclear Information System (INIS)

    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.)

  19. Applied metabolomics in drug discovery.

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  2. Feedback-Driven Dynamic Invariant Discovery

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  4. Why should we publish Linked Data?

    Science.gov (United States)

    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).

  5. Fiftieth anniversary of major discoveries at the Cavendish Laboratory

    International Nuclear Information System (INIS)

    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

  6. Exploring relation types for literature-based discovery.

    Science.gov (United States)

    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.

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

    NARCIS (Netherlands)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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…

  10. Machine-assisted discovery of relationships in astronomy

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  14. Computational neuropharmacology: dynamical approaches in drug discovery.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. Volatility Discovery

    DEFF Research Database (Denmark)

    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....

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

    Science.gov (United States)

    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.

  2. Unsupervised action classification using space-time link analysis

    DEFF Research Database (Denmark)

    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...

  3. Rough – Granular Computing knowledge discovery models

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  8. Linked Metadata - lightweight semantics for data integration (Invited)

    Science.gov (United States)

    Hendler, J. A.

    2013-12-01

    fly integration may prefer to do more traditional data queries and then convert and link the 'views' returned at retrieval time, providing another means of using the linked data infrastructure without having to convert whole datasets to triples to provide linking. Web companies have been taking advantage of 'lightweight' semantic metadata for search quality and optimization (cf. schema.org), linking networks within and without web sites (cf. Facebook's Open Graph Protocol), and in doing various kinds of advertisement and user modeling across datasets. Scientific metadata, on the other hand, has traditionally been geared at being largescale and highly descriptive, and scientific ontologies have been aimed at high expressivity, essentially providing complex reasoning services rather than the less expressive vocabularies needed for data discovery and simple mappings that can allow humans (or more complex systems) when full scale integration is needed. Although this work is just the beginning for providing integration, as the community creates more and more datasets, discovery of these data resources on the Web becomes a crucial starting place. Simple descriptors, that can be combined with textual fields and/or common community vocabularies, can be a great starting place on bringing scientific data into the Web of Data that is growing in other communities. References: [1] Pouchard, Line C., et al. "A Linked Science investigation: enhancing climate change data discovery with semantic technologies." Earth science informatics 6.3 (2013): 175-185.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    ... 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 ...

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

    Science.gov (United States)

    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.

  12. Tick-borne pathogen – Reversed and conventional discovery of disease

    Directory of Open Access Journals (Sweden)

    Ellen eTijsse Klasen

    2014-07-01

    Full Text Available Molecular methods have increased the number of known microorganisms associated with ticks significantly. Some of these newly identified microorganisms are readily linked to human disease while others are yet unknown to cause human disease. The face of tick-borne disease discovery has changed with more diseases now being discovered in a ‘reversed way’, detecting disease cases only years after the tick-borne microorganism was first discovered. Compared to the conventional discovery of infectious diseases, this order of discoveries presents researchers with new challenges. Especially estimating public health risks of such agents is challenging, as case definitions and diagnostic procedures may initially be missing. We discuss the advantages and shortcomings of molecular methods, serology, epidemiological studies that might be used to study some fundamental questions regarding newly identified tick-borne diseases. With increased tick-exposure and improved detection methods, more tick-borne microorganisms will be added to the list of pathogens causing disease in humans in future.

  13. Business Model Discovery by Technology Entrepreneurs

    Directory of Open Access Journals (Sweden)

    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

    CERN Multimedia

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    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...

  17. Analysis on Big Data Problems and Technique Supports of Archives Informatization

    Directory of Open Access Journals (Sweden)

    Du Xiaoyan

    2017-06-01

    Full Text Available [Purpose/significance] The realistic questions of the archives informatization management are faced with data size rapidly increasing, and their types and structures more diverse and complex. [Method/process] Based on the essential attribute of archives in this paper, the big data characteristics of digital archives in their storage and utilization links were analyzed, and the support of new big data techniques in the course of archives informatization, and their applications to the storage and utilization of digital archives and knowledge discovery were researched. [Result/conclusion] Modern processing technology for big data would not only bring certain supports for the management of archives informatization, but also promote the development of its theory and practice.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    NARCIS (Netherlands)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Topology Discovery Using Cisco Discovery Protocol

    OpenAIRE

    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 ...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Earth2Class Overview: An Innovative Program Linking Classroom Educators and Research Scientists

    Science.gov (United States)

    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.

  5. Fragment-based drug discovery and its application to challenging drug targets.

    Science.gov (United States)

    Price, Amanda J; Howard, Steven; Cons, Benjamin D

    2017-11-08

    Fragment-based drug discovery (FBDD) is a technique for identifying low molecular weight chemical starting points for drug discovery. Since its inception 20 years ago, FBDD has grown in popularity to the point where it is now an established technique in industry and academia. The approach involves the biophysical screening of proteins against collections of low molecular weight compounds (fragments). Although fragments bind to proteins with relatively low affinity, they form efficient, high quality binding interactions with the protein architecture as they have to overcome a significant entropy barrier to bind. Of the biophysical methods available for fragment screening, X-ray protein crystallography is one of the most sensitive and least prone to false positives. It also provides detailed structural information of the protein-fragment complex at the atomic level. Fragment-based screening using X-ray crystallography is therefore an efficient method for identifying binding hotspots on proteins, which can then be exploited by chemists and biologists for the discovery of new drugs. The use of FBDD is illustrated here with a recently published case study of a drug discovery programme targeting the challenging protein-protein interaction Kelch-like ECH-associated protein 1:nuclear factor erythroid 2-related factor 2. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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

    Science.gov (United States)

    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.

  7. Linked data management

    CERN Document Server

    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...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  10. X-Ray Astronomy Discovery Experiments, III*

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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

  14. Hybrid Monte Carlo algorithm with fat link fermion actions

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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…

  16. 14 CFR 406.143 - Discovery.

    Science.gov (United States)

    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...

  17. Broadcast Expenses Controlling Techniques in Mobile Ad-hoc Networks: A Survey

    Directory of Open Access Journals (Sweden)

    Naeem Ahmad

    2016-07-01

    Full Text Available The blind flooding of query packets in route discovery more often characterizes the broadcast storm problem, exponentially increases energy consumption of intermediate nodes and congests the entire network. In such a congested network, the task of establishing the path between resources may become very complex and unwieldy. An extensive research work has been done in this area to improve the route discovery phase of routing protocols by reducing broadcast expenses. The purpose of this study is to provide a comparative analysis of existing broadcasting techniques for the route discovery phase, in order to bring about an efficient broadcasting technique for determining the route with minimum conveying nodes in ad-hoc networks. The study is designed to highlight the collective merits and demerits of such broadcasting techniques along with certain conclusions that would contribute to the choice of broadcasting techniques.

  18. Higgs Discovery

    DEFF Research Database (Denmark)

    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...

  19. Application of PBPK modelling in drug discovery and development at Pfizer.

    Science.gov (United States)

    Jones, Hannah M; Dickins, Maurice; Youdim, Kuresh; Gosset, James R; Attkins, Neil J; Hay, Tanya L; Gurrell, Ian K; Logan, Y Raj; Bungay, Peter J; Jones, Barry C; Gardner, Iain B

    2012-01-01

    Early prediction of human pharmacokinetics (PK) and drug-drug interactions (DDI) in drug discovery and development allows for more informed decision making. Physiologically based pharmacokinetic (PBPK) modelling can be used to answer a number of questions throughout the process of drug discovery and development and is thus becoming a very popular tool. PBPK models provide the opportunity to integrate key input parameters from different sources to not only estimate PK parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. Using examples from the literature and our own company, we have shown how PBPK techniques can be utilized through the stages of drug discovery and development to increase efficiency, reduce the need for animal studies, replace clinical trials and to increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however, some limitations need to be addressed to realize its application and utility more broadly.

  20. Discovery of Five Probable Novae in M81

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    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)

  2. Microwave Photonics Techniques Supporting Flexible Wireless Communications Links

    DEFF Research Database (Denmark)

    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...

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

    Science.gov (United States)

    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.

  4. Beyond Discovery

    DEFF Research Database (Denmark)

    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...

  5. "Eureka, Eureka!" Discoveries in Science

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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.

  7. Drug Discovery Gets a Boost from Data Science.

    Science.gov (United States)

    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.

  8. 30 CFR 44.24 - Discovery.

    Science.gov (United States)

    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...

  9. 19 CFR 356.20 - Discovery.

    Science.gov (United States)

    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...

  10. Chemical Discovery

    Science.gov (United States)

    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 Mondays: Surveyors' Tools

    CERN Multimedia

    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...

  12. 24 CFR 180.500 - Discovery.

    Science.gov (United States)

    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...

  13. 22 CFR 224.21 - Discovery.

    Science.gov (United States)

    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...

  14. Linking lab and field

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

    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...

  16. 19 CFR 207.109 - Discovery.

    Science.gov (United States)

    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...

  17. 15 CFR 25.21 - Discovery.

    Science.gov (United States)

    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...

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

    OpenAIRE

    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 ...

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

    Science.gov (United States)

    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

  20. Linked Data: Forming Partnerships at the Data Layer

    Science.gov (United States)

    Shepherd, A.; Chandler, C. L.; Arko, R. A.; Jones, M. B.; Hitzler, P.; Janowicz, K.; Krisnadhi, A.; Schildhauer, M.; Fils, D.; Narock, T.; Groman, R. C.; O'Brien, M.; Patton, E. W.; Kinkade, D.; Rauch, S.

    2015-12-01

    The challenges presented by big data are straining data management software architectures of the past. For smaller existing data facilities, the technical refactoring of software layers become costly to scale across the big data landscape. In response to these challenges, data facilities will need partnerships with external entities for improved solutions to perform tasks such as data cataloging, discovery and reuse, and data integration and processing with provenance. At its surface, the concept of linked open data suggests an uncalculated altruism. Yet, in his concept of five star open data, Tim Berners-Lee explains the strategic costs and benefits of deploying linked open data from the perspective of its consumer and producer - a data partnership. The Biological and Chemical Oceanography Data Management Office (BCO-DMO) addresses some of the emerging needs of its research community by partnering with groups doing complementary work and linking their respective data layers using linked open data principles. Examples will show how these links, explicit manifestations of partnerships, reduce technical debt and provide a swift flexibility for future considerations.

  1. 39 CFR 963.14 - Discovery.

    Science.gov (United States)

    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...

  2. Reuse-oriented common structure discovery in assembly models

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Reuse-oriented common structure discovery in assembly models

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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…

  6. Next-Generation Sequencing Approaches in Genome-Wide Discovery of Single Nucleotide Polymorphism Markers Associated with Pungency and Disease Resistance in Pepper.

    Science.gov (United States)

    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.

  7. Next-Generation Sequencing Approaches in Genome-Wide Discovery of Single Nucleotide Polymorphism Markers Associated with Pungency and Disease Resistance in Pepper

    Directory of Open Access Journals (Sweden)

    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.

  8. Shotgun Proteomics and Biomarker Discovery

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

    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.

  10. Service discovery from observed behavior while guaranteeing deadlock freedom in collaborations

    NARCIS (Netherlands)

    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--

  11. Service discovery from observed behavior while guaranteeing deadlock freedom in collaborations

    NARCIS (Netherlands)

    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

  12. Current status of accelerated corneal cross-linking

    Directory of Open Access Journals (Sweden)

    Michael Mrochen

    2013-01-01

    Full Text Available Corneal cross-linking with riboflavin is a technique to stabilize or reduce corneal ectasia, in diseases such as keratoconus and post-laser-assisted in situ keratomileusis (LASIK ectasia. There is an interest by patient as well as clinicians to reduce the overall treatment time. Especially, the introduction of corneal cross-linking in combination with corneal laser surgery demands a shorter treatment time to assure a sufficient patient flow. The principles and techniques of accelerated corneal cross-linking is discussed.

  13. Enzymatic cellulose oxidation is linked to lignin by long-range electron transfer

    DEFF Research Database (Denmark)

    Westereng, Bjorge; Cannella, David; Wittrup Agger, Jane

    2015-01-01

    cell walls. Electron transfer was confirmed by electron paramagnetic resonance spectroscopy showing that LPMO activity on cellulose changes the level of unpaired electrons in the lignin. The discovery of a long-range electron transfer mechanism links the biodegradation of cellulose and lignin and sheds...

  14. Venomics-Accelerated Cone Snail Venom Peptide Discovery

    Science.gov (United States)

    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

  15. Venomics-Accelerated Cone Snail Venom Peptide Discovery

    Directory of Open Access Journals (Sweden)

    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.

  16. Usability of Discovery Portals

    OpenAIRE

    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...

  17. Fragment-based approaches to anti-HIV drug discovery: state of the art and future opportunities.

    Science.gov (United States)

    Huang, Boshi; Kang, Dongwei; Zhan, Peng; Liu, Xinyong

    2015-12-01

    The search for additional drugs to treat HIV infection is a continuing effort due to the emergence and spread of HIV strains resistant to nearly all current drugs. The recent literature reveals that fragment-based drug design/discovery (FBDD) has become an effective alternative to conventional high-throughput screening strategies for drug discovery. In this critical review, the authors describe the state of the art in FBDD strategies for the discovery of anti-HIV drug-like compounds. The article focuses on fragment screening techniques, direct fragment-based design and early hit-to-lead progress. Rapid progress in biophysical detection and in silico techniques has greatly aided the application of FBDD to discover candidate agents directed at a variety of anti-HIV targets. Growing evidence suggests that structural insights on key proteins in the HIV life cycle can be applied in the early phase of drug discovery campaigns, providing valuable information on the binding modes and efficiently prompting fragment hit-to-lead progression. The combination of structural insights with improved methodologies for FBDD, including the privileged fragment-based reconstruction approach, fragment hybridization based on crystallographic overlays, fragment growth exploiting dynamic combinatorial chemistry, and high-speed fragment assembly via diversity-oriented synthesis followed by in situ screening, offers the possibility of more efficient and rapid discovery of novel drugs for HIV-1 prevention or treatment. Though the use of FBDD in anti-HIV drug discovery is still in its infancy, it is anticipated that anti-HIV agents developed via fragment-based strategies will be introduced into the clinic in the future.

  18. A Multimodal Data Analysis Approach for Targeted Drug Discovery Involving Topological Data Analysis (TDA).

    Science.gov (United States)

    Alagappan, Muthuraman; Jiang, Dadi; Denko, Nicholas; Koong, Albert C

    In silico drug discovery refers to a combination of computational techniques that augment our ability to discover drug compounds from compound libraries. Many such techniques exist, including virtual high-throughput screening (vHTS), high-throughput screening (HTS), and mechanisms for data storage and querying. However, presently these tools are often used independent of one another. In this chapter, we describe a new multimodal in silico technique for the hit identification and lead generation phases of traditional drug discovery. Our technique leverages the benefits of three independent methods-virtual high-throughput screening, high-throughput screening, and structural fingerprint analysis-by using a fourth technique called topological data analysis (TDA). We describe how a compound library can be independently tested with vHTS, HTS, and fingerprint analysis, and how the results can be transformed into a topological data analysis network to identify compounds from a diverse group of structural families. This process of using TDA or similar clustering methods to identify drug leads is advantageous because it provides a mechanism for choosing structurally diverse compounds while maintaining the unique advantages of already established techniques such as vHTS and HTS.

  19. Discovery of a probable galaxy with a redshift of 3.218

    International Nuclear Information System (INIS)

    Djorgovski, S.; Spinard, H.; McCarthy, P.; Strauss, M.A.

    1985-01-01

    We report the discovery of a narrow emission line object, probably a galaxy, with a redshift of 3.218. The object is a companion to the quasar PKS 1614+051, which is at a redshift of 3.209. This is the most distant non--QSO, non--gravitationally lensed object presently known by a large margin. Its properties are consistent with those expected of a high-redshift galaxy. This object has an age of only a few percent of the present age of the universe. The object was discovered with a novel technique, which promises to push studies of distant galaxies to redshifts as high as those of the most distant quasars known, and which may eventually lead to the discovery of primeval galaxies. This discovery opens the way for studies of galaxies beyond z = 3, which should prove invaluable for observational cosmology

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  2. Genome engineering for microbial natural product discovery.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  5. 19 CFR 354.10 - Discovery.

    Science.gov (United States)

    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...

  6. 36 CFR 1150.63 - Discovery.

    Science.gov (United States)

    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...

  7. 37 CFR 11.52 - Discovery.

    Science.gov (United States)

    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...

  8. Usability of Discovery Portals

    NARCIS (Netherlands)

    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

  9. 14 CFR 16.213 - Discovery.

    Science.gov (United States)

    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...

  10. 28 CFR 76.21 - Discovery.

    Science.gov (United States)

    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...

  11. 40 CFR 27.21 - Discovery.

    Science.gov (United States)

    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...

  12. 37 CFR 41.150 - Discovery.

    Science.gov (United States)

    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...

  13. 14 CFR 13.220 - Discovery.

    Science.gov (United States)

    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...

  14. 49 CFR 604.38 - Discovery.

    Science.gov (United States)

    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...

  15. 15 CFR 719.10 - Discovery.

    Science.gov (United States)

    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...

  16. 24 CFR 26.18 - Discovery.

    Science.gov (United States)

    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...

  17. 42 CFR 426.532 - Discovery.

    Science.gov (United States)

    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...

  18. 49 CFR 1503.633 - Discovery.

    Science.gov (United States)

    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. 14 CFR 1264.120 - Discovery.

    Science.gov (United States)

    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...

  20. 22 CFR 128.6 - Discovery.

    Science.gov (United States)

    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...

  1. 24 CFR 26.42 - Discovery.

    Science.gov (United States)

    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...

  2. 49 CFR 386.37 - Discovery.

    Science.gov (United States)

    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...

  3. 29 CFR 1955.32 - Discovery.

    Science.gov (United States)

    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...

  4. Rediscovering Don Swanson: The Past, Present and Future of Literature-based Discovery

    Directory of Open Access Journals (Sweden)

    Neil R. Smalheiser

    2017-12-01

    Full Text Available Purpose: The late Don R. Swanson was well appreciated during his lifetime as Dean of the Graduate Library School at University of Chicago, as winner of the American Society for Information Science Award of Merit for 2000, and as author of many seminal articles. In this informal essay, I will give my personal perspective on Don’s contributions to science, and outline some current and future directions in literature-based discovery that are rooted in concepts that he developed. Design/methodology/approach: Personal recollections and literature review. Findings: The Swanson A-B-C model of literature-based discovery has been successfully used by laboratory investigators analyzing their findings and hypotheses. It continues to be a fertile area of research in a wide range of application areas including text mining, drug repurposing, studies of scientific innovation, knowledge discovery in databases, and bioinformatics. Recently, additional modes of discovery that do not follow the A-B-C model have also been proposed and explored (e.g. so-called storytelling, gaps, analogies, link prediction, negative consensus, outliers, and revival of neglected or discarded research questions. Research limitations: This paper reflects the opinions of the author and is not a comprehensive nor technically based review of literature-based discovery. Practical implications: The general scientific public is still not aware of the availability of tools for literature-based discovery. Our Arrowsmith project site maintains a suite of discovery tools that are free and open to the public (http://arrowsmith.psych.uic.edu, as does BITOLA which is maintained by Dmitar Hristovski (http:// http://ibmi.mf.uni-lj.si/bitola, and Epiphanet which is maintained by Trevor Cohen (http://epiphanet.uth.tmc.edu/. Bringing user-friendly tools to the public should be a high priority, since even more than advancing basic research in informatics, it is vital that we ensure that scientists

  5. 42 CFR 426.432 - Discovery.

    Science.gov (United States)

    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...

  6. 10 CFR 13.21 - Discovery.

    Science.gov (United States)

    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...

  7. 49 CFR 1121.2 - Discovery.

    Science.gov (United States)

    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...

  8. 38 CFR 42.21 - Discovery.

    Science.gov (United States)

    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...

  9. 22 CFR 521.21 - Discovery.

    Science.gov (United States)

    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...

  10. 31 CFR 10.71 - Discovery.

    Science.gov (United States)

    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...

  11. 39 CFR 955.15 - Discovery.

    Science.gov (United States)

    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...

  12. 43 CFR 35.21 - Discovery.

    Science.gov (United States)

    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...

  13. 15 CFR 766.9 - Discovery.

    Science.gov (United States)

    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...

  14. Advances in immobilized artificial membrane (IAM) chromatography for novel drug discovery.

    Science.gov (United States)

    Tsopelas, Fotios; Vallianatou, Theodosia; Tsantili-Kakoulidou, Anna

    2016-01-01

    The development of immobilized artificial membrane (IAM) chromatography has unfolded new perspectives for the use of chromatographic techniques in drug discovery, combining simulation of the environment of cell membranes with rapid measurements. The present review describes the characteristics of phosphatidylcholine-based stationary phases and analyses the molecular factors governing IAM retention in comparison to n-octanol-water and liposomes partitioning systems as well as to reversed phase chromatography. Other biomimetic stationary phases are also briefly discussed. The potential of IAM chromatography to model permeability through the main physiological barriers and drug membrane interactions is outlined. Further applications to calculate complex pharmacokinetic properties, related to tissue binding, and to screen drug candidates for phospholipidosis, as well as to estimate cell accumulation/retention are surveyed. The ambivalent nature of IAM chromatography, as a border case between passive diffusion and binding, defines its multiple potential applications. However, despite its successful performance in many permeability and drug-membrane interactions studies, IAM chromatography is still used as a supportive and not a stand-alone technique. Further studies looking at IAM chromatography in different biological processes are still required if this technique is to have a more focused and consistent application in drug discovery.

  15. A fragment-based approach leading to the discovery of a novel binding site and the selective CK2 inhibitor CAM4066.

    Science.gov (United States)

    De Fusco, Claudia; Brear, Paul; Iegre, Jessica; Georgiou, Kathy Hadje; Sore, Hannah F; Hyvönen, Marko; Spring, David R

    2017-07-01

    Recently we reported the discovery of a potent and selective CK2α inhibitor CAM4066. This compound inhibits CK2 activity by exploiting a pocket located outside the ATP binding site (αD pocket). Here we describe in detail the journey that led to the discovery of CAM4066 using the challenging fragment linking strategy. Specifically, we aimed to develop inhibitors by linking a high-affinity fragment anchored in the αD site to a weakly binding warhead fragment occupying the ATP site. Moreover, we describe the remarkable impact that molecular modelling had on the development of this novel chemical tool. The work described herein shows potential for the development of a novel class of CK2 inhibitors. Copyright © 2017. Published by Elsevier Ltd.

  16. A Cross-Layer Route Discovery Framework for Mobile Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Wu Jieyi

    2005-01-01

    Full Text Available Most reactive routing protocols in MANETs employ a random delay between rebroadcasting route requests (RREQ in order to avoid "broadcast storms." However this can lead to problems such as "next hop racing" and "rebroadcast redundancy." In addition to this, existing routing protocols for MANETs usually take a single routing strategy for all flows. This may lead to inefficient use of resources. In this paper we propose a cross-layer route discovery framework (CRDF to address these problems by exploiting the cross-layer information. CRDF solves the above problems efficiently and enables a new technique: routing strategy automation (RoSAuto. RoSAuto refers to the technique that each source node automatically decides the routing strategy based on the application requirements and each intermediate node further adapts the routing strategy so that the network resource usage can be optimized. To demonstrate the effectiveness and the efficiency of CRDF, we design and evaluate a macrobian route discovery strategy under CRDF.

  17. Discovery Mondays - Men of fire: the fire brigade show their mettle

    CERN Multimedia

    2004-01-01

    Flashover and backdraught, these technical terms refer to two of the most dangerous phenomena associated with fires. In order to train in dealing with them, in the course of their fire fighting duties the CERN fire brigade use special simulation equipment. The demonstrations are rather spectacular... Thrills are therefore guaranteed at the next Discovery Monday on 2 February! In the course of the evening, you will see fire-fighters demonstrate climbing techniques including abseiling, a method they would have to use to access underground structures on the CERN site in the event of an accident. The accomplished climbers (the Hazardous Environments Response Team) will provide detailed explanations of the rescue techniques and procedures they use in tunnels and hazardous environments. CERN firemen simulate the backdraft phenomena for training. The demonstration, which you will have the opportunity to observe, on the next Discovery Monday, is spectacular. However, the remit of the CERN fire brigade goes well b...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  20. 13 CFR 134.213 - Discovery.

    Science.gov (United States)

    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...

  1. 31 CFR 16.21 - Discovery.

    Science.gov (United States)

    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...

  2. Automatic discovery of cross-family sequence features associated with protein function

    Directory of Open Access Journals (Sweden)

    Krings Andrea

    2006-01-01

    knowledge discovery in annotated sequence data. The technique is able to identify functionally important sequence features and does not require expert knowledge. By viewing protein function from a sequence perspective, the approach is also suitable for discovering unexpected links between biological processes, such as the recently discovered role of ubiquitination in transcription.

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

    Science.gov (United States)

    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.

  4. Multi-dimensional discovery of biomarker and phenotype complexes

    Directory of Open Access Journals (Sweden)

    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.

  5. Decades of Discovery

    Science.gov (United States)

    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.

  6. Energy Efficient Link Aware Routing with Power Control in Wireless Ad Hoc Networks.

    Science.gov (United States)

    Katiravan, Jeevaa; Sylvia, D; Rao, D Srinivasa

    2015-01-01

    In wireless ad hoc networks, the traditional routing protocols make the route selection based on minimum distance between the nodes and the minimum number of hop counts. Most of the routing decisions do not consider the condition of the network such as link quality and residual energy of the nodes. Also, when a link failure occurs, a route discovery mechanism is initiated which incurs high routing overhead. If the broadcast nature and the spatial diversity of the wireless communication are utilized efficiently it becomes possible to achieve improvement in the performance of the wireless networks. In contrast to the traditional routing scheme which makes use of a predetermined route for packet transmission, such an opportunistic routing scheme defines a predefined forwarding candidate list formed by using single network metrics. In this paper, a protocol is proposed which uses multiple metrics such as residual energy and link quality for route selection and also includes a monitoring mechanism which initiates a route discovery for a poor link, thereby reducing the overhead involved and improving the throughput of the network while maintaining network connectivity. Power control is also implemented not only to save energy but also to improve the network performance. Using simulations, we show the performance improvement attained in the network in terms of packet delivery ratio, routing overhead, and residual energy of the network.

  7. Energy Efficient Link Aware Routing with Power Control in Wireless Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Jeevaa Katiravan

    2015-01-01

    Full Text Available In wireless ad hoc networks, the traditional routing protocols make the route selection based on minimum distance between the nodes and the minimum number of hop counts. Most of the routing decisions do not consider the condition of the network such as link quality and residual energy of the nodes. Also, when a link failure occurs, a route discovery mechanism is initiated which incurs high routing overhead. If the broadcast nature and the spatial diversity of the wireless communication are utilized efficiently it becomes possible to achieve improvement in the performance of the wireless networks. In contrast to the traditional routing scheme which makes use of a predetermined route for packet transmission, such an opportunistic routing scheme defines a predefined forwarding candidate list formed by using single network metrics. In this paper, a protocol is proposed which uses multiple metrics such as residual energy and link quality for route selection and also includes a monitoring mechanism which initiates a route discovery for a poor link, thereby reducing the overhead involved and improving the throughput of the network while maintaining network connectivity. Power control is also implemented not only to save energy but also to improve the network performance. Using simulations, we show the performance improvement attained in the network in terms of packet delivery ratio, routing overhead, and residual energy of the network.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Discovery and the atom

    International Nuclear Information System (INIS)

    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)

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

    Science.gov (United States)

    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.

  11. Linked Ocean Data

    Science.gov (United States)

    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.

  12. A statistical model for telecommunication link design

    Science.gov (United States)

    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. 29 CFR 2700.56 - Discovery; general.

    Science.gov (United States)

    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...

  14. Met1-linked Ubiquitination in Immune Signalling

    DEFF Research Database (Denmark)

    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...

  15. Discovery and first models of the quadruply lensed quasar SDSS J1433+6007

    Science.gov (United States)

    Agnello, Adriano; Grillo, Claudio; Jones, Tucker; Treu, Tommaso; Bonamigo, Mario; Suyu, Sherry H.

    2018-03-01

    We report the discovery of the quadruply lensed quasar SDSS J1433+6007 (RA = 14:33:22.8, Dec. = +60:07:13.44), mined in the SDSS DR12 photometric catalogues using a novel outlier-selection technique, without prior spectroscopic or ultraviolet excess information. Discovery data obtained at the Nordic Optical Telescope (La Palma) show nearly identical quasar spectra at zs = 2.737 ± 0.003 and four quasar images in a fold configuration, one of which sits on a blue arc, with maximum separation 3.6 arcsec. The deflector redshift is zl = 0.407 ± 0.002, from Keck-ESI spectra. We describe the selection procedure, discovery and follow-up, image positions and BVRi magnitudes, and first results and forecasts from lens model fit to the relative image positions.

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

    Science.gov (United States)

    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.

  17. High-throughput platform assay technology for the discovery of pre-microrna-selective small molecule probes.

    Science.gov (United States)

    Lorenz, Daniel A; Song, James M; Garner, Amanda L

    2015-01-21

    MicroRNAs (miRNA) play critical roles in human development and disease. As such, the targeting of miRNAs is considered attractive as a novel therapeutic strategy. A major bottleneck toward this goal, however, has been the identification of small molecule probes that are specific for select RNAs and methods that will facilitate such discovery efforts. Using pre-microRNAs as proof-of-concept, herein we report a conceptually new and innovative approach for assaying RNA-small molecule interactions. Through this platform assay technology, which we term catalytic enzyme-linked click chemistry assay or cat-ELCCA, we have designed a method that can be implemented in high throughput, is virtually free of false readouts, and is general for all nucleic acids. Through cat-ELCCA, we envision the discovery of selective small molecule ligands for disease-relevant miRNAs to promote the field of RNA-targeted drug discovery and further our understanding of the role of miRNAs in cellular biology.

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

    International Nuclear Information System (INIS)

    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)

  19. Managing Your Team's Weakest Link.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.…

  1. Linked data meets ontology matching: enhancing data linking through ontology alignments

    OpenAIRE

    Scharffe , François; Euzenat , Jérôme

    2011-01-01

    scharffe2011b; International audience; The Web of data consists of publishing data on the Web in such a way that they can be connected together and interpreted. It is thus critical to establish links between these data, both for the Web of data and for the Semantic Web that it contributes to feed. We consider here the various techniques which have been developed for that purpose and analyze their commonalities and differences. This provides a general framework that the diverse data linking sy...

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

    Science.gov (United States)

    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

  3. 29 CFR 2200.208 - Discovery.

    Science.gov (United States)

    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...

  4. 47 CFR 65.105 - Discovery.

    Science.gov (United States)

    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...

  5. 49 CFR 209.313 - Discovery.

    Science.gov (United States)

    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...

  6. Strategies for Discovery of Small Molecule Radiation Protectors and Radiation Mitigators

    Directory of Open Access Journals (Sweden)

    Joel S Greenberger

    2012-01-01

    Full Text Available Mitochondrial targeted radiation damage protectors (delivered prior to irradiation and mitigators (delivered after irradiation, but before the appearance of symptoms associated with radiation syndrome have been a recent focus in drug discovery for 1 normal tissue radiation protection during fractionated radiotherapy, and 2 radiation terrorism counter measures. Several categories of such molecules have been discovered: nitroxide-linked hybrid molecules, including GS-nitroxide, GS-nitric oxide synthase inhibitors, p53/mdm2/mdm4 inhibitors, and pharmaceutical agents including inhibitors of the phosphoinositide-3-kinase pathway and the anti-seizure medicine, carbamazepine. Evaluation of potential new irradiation dose modifying molecules to protect normal tissue includes: clonagenic radiation survival curves; assays for apoptosis and DNA repair, and irradiation-induced depletion of antioxidant stores. Studies of organ specific radioprotection and in total body irradiation-induced hematopoietic syndrome in the mouse model for protection/mitigation facilitate rational means by which to move candidate small molecule drugs along the drug discovery pipeline into clinical development.

  7. Strategies for Discovery of Small Molecule Radiation Protectors and Radiation Mitigators

    Energy Technology Data Exchange (ETDEWEB)

    Greenberger, Joel S.; Clump, David [Radiation Oncology Department, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Kagan, Valerian [Environmental and Occupational Health Department, University of Pittsburgh, Pittsburgh, PA (United States); Bayir, Hülya [Critical Care Medicine Department, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Lazo, John S. [Pharmacology Department, University of Virginia, Charlottesville, VA (United States); Wipf, Peter [Department of Chemistry, Accelerated Chemical Discovery Center, University of Pittsburgh, Pittsburgh, PA (United States); Li, Song; Gao, Xiang [Pharmaceutical Science Department, University of Pittsburgh, Pittsburgh, PA (United States); Epperly, Michael W., E-mail: greenbergerjs@upmc.edu [Radiation Oncology Department, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States)

    2012-01-13

    Mitochondrial targeted radiation damage protectors (delivered prior to irradiation) and mitigators (delivered after irradiation, but before the appearance of symptoms associated with radiation syndrome) have been a recent focus in drug discovery for (1) normal tissue radiation protection during fractionated radiotherapy, and (2) radiation terrorism counter measures. Several categories of such molecules have been discovered: nitroxide-linked hybrid molecules, including GS-nitroxide, GS-nitric oxide synthase inhibitors, p53/mdm2/mdm4 inhibitors, and pharmaceutical agents including inhibitors of the phosphoinositide-3-kinase pathway and the anti-seizure medicine, carbamazepine. Evaluation of potential new radiation dose modifying molecules to protect normal tissue includes: clonogenic radiation survival curves, assays for apoptosis and DNA repair, and irradiation-induced depletion of antioxidant stores. Studies of organ specific radioprotection and in total body irradiation-induced hematopoietic syndrome in the mouse model for protection/mitigation facilitate rational means by which to move candidate small molecule drugs along the drug discovery pipeline into clinical development.

  8. Quantifying the Ease of Scientific Discovery.

    Science.gov (United States)

    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.

  9. 15 CFR 280.210 - Discovery.

    Science.gov (United States)

    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...

  10. Fragment-Based Drug Discovery in the Bromodomain and Extra-Terminal Domain Family.

    Science.gov (United States)

    Radwan, Mostafa; Serya, Rabah

    2017-08-01

    Bromodomain and extra-terminal domain (BET) inhibition has emerged recently as a potential therapeutic target for the treatment of many human disorders such as atherosclerosis, inflammatory disorders, chronic obstructive pulmonary disease (COPD), some viral infections, and cancer. Since the discovery of the two potent inhibitors, I-BET762 and JQ1, different research groups have used different techniques to develop novel potent and selective inhibitors. In this review, we will be concerned with the trials that used fragment-based drug discovery (FBDD) approaches to discover or optimize BET inhibitors, also showing fragments that can be further optimized in future projects to reach novel potent BET inhibitors. © 2017 Deutsche Pharmazeutische Gesellschaft.

  11. 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.

    Science.gov (United States)

    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.

  12. 10 CFR 1013.21 - Discovery.

    Science.gov (United States)

    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...

  13. 37 CFR 2.120 - Discovery.

    Science.gov (United States)

    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...

  14. 46 CFR 550.502 - Discovery.

    Science.gov (United States)

    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...

  15. 15 CFR 785.8 - Discovery.

    Science.gov (United States)

    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...

  16. 22 CFR 35.21 - Discovery.

    Science.gov (United States)

    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...

  17. 45 CFR 96.65 - Discovery.

    Science.gov (United States)

    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. 49 CFR 31.21 - Discovery.

    Science.gov (United States)

    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...

  19. 43 CFR 4.1130 - Discovery methods.

    Science.gov (United States)

    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...

  20. 6 CFR 13.21 - Discovery.

    Science.gov (United States)

    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...

  1. 45 CFR 99.23 - Discovery.

    Science.gov (United States)

    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...

  2. 20 CFR 355.21 - Discovery.

    Science.gov (United States)

    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...

  3. 10 CFR 2.1018 - Discovery.

    Science.gov (United States)

    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...

  4. 28 CFR 71.21 - Discovery.

    Science.gov (United States)

    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...

  5. 13 CFR 134.310 - Discovery.

    Science.gov (United States)

    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...

  6. 34 CFR 33.21 - Discovery.

    Science.gov (United States)

    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...

  7. 28 CFR 18.7 - Discovery.

    Science.gov (United States)

    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...

  8. 7 CFR 1.322 - Discovery.

    Science.gov (United States)

    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...

  9. 45 CFR 1386.103 - Discovery.

    Science.gov (United States)

    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...

  10. 45 CFR 79.21 - Discovery.

    Science.gov (United States)

    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...

  11. 12 CFR 308.520 - Discovery.

    Science.gov (United States)

    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...

  12. 47 CFR 1.729 - Discovery.

    Science.gov (United States)

    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...

  13. 7 CFR 283.12 - Discovery.

    Science.gov (United States)

    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...

  14. Big Data in Drug Discovery.

    Science.gov (United States)

    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.

  15. Discovery of Uniformly Expanding Universe

    Directory of Open Access Journals (Sweden)

    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.

  16. IMG-ABC: An Atlas of Biosynthetic Gene Clusters to Fuel the Discovery of Novel Secondary Metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Chen, I-Min; Chu, Ken; Ratner, Anna; Palaniappan, Krishna; Huang, Jinghua; Reddy, T. B.K.; Cimermancic, Peter; Fischbach, Michael; Ivanova, Natalia; Markowitz, Victor; Kyrpides, Nikos; Pati, Amrita

    2014-10-28

    In the discovery of secondary metabolites (SMs), large-scale analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of relevant computational resources. We present IMG-ABC (https://img.jgi.doe.gov/abc/) -- An Atlas of Biosynthetic gene Clusters within the Integrated Microbial Genomes (IMG) system1. IMG-ABC is a rich repository of both validated and predicted biosynthetic clusters (BCs) in cultured isolates, single-cells and metagenomes linked with the SM chemicals they produce and enhanced with focused analysis tools within IMG. The underlying scalable framework enables traversal of phylogenetic dark matter and chemical structure space -- serving as a doorway to a new era in the discovery of novel molecules.

  17. 42 CFR 1005.7 - Discovery.

    Science.gov (United States)

    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...

  18. 29 CFR 1603.210 - Discovery.

    Science.gov (United States)

    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...

  19. 45 CFR 150.435 - Discovery.

    Science.gov (United States)

    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...

  20. 34 CFR 81.16 - Discovery.

    Science.gov (United States)

    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...

  1. 29 CFR 1905.25 - Discovery.

    Science.gov (United States)

    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...

  2. 12 CFR 1780.26 - Discovery.

    Science.gov (United States)

    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...

  3. 45 CFR 160.516 - Discovery.

    Science.gov (United States)

    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...

  4. 42 CFR 430.86 - Discovery.

    Science.gov (United States)

    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...

  5. Space technology in the discovery and development of mineral and energy resources

    Science.gov (United States)

    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.

  6. Teaching Tip: Using Rapid Game Prototyping for Exploring Requirements Discovery and Modeling

    Science.gov (United States)

    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…

  7. Neighbor discovery in multi-hop wireless networks: evaluation and dimensioning with interferences considerations

    Directory of Open Access Journals (Sweden)

    Elyes Ben Hamida

    2008-04-01

    Full Text Available In this paper, we study the impact of collisions and interferences on a neighbor discovery process in the context of multi-hop wireless networks. We consider three models in which interferences and collisions are handled in very different ways. From an ideal channel where simultaneous transmissions do not interfere, we derive an alternate channel where simultaneous transmissions are considered two-by-two under the form of collisions, to finally reach a more realistic channel where simultaneous transmissions are handled under the form of shot-noise interferences. In these models, we analytically compute the link probability success between two neighbors as well as the expected number of nodes that correctly receive a Hello packet. Using this analysis, we show that if the neighbor discovery process is asymptotically equivalent in the three models, it offers very different behaviors locally in time. In particular, the scalability of the process is not the same depending on the way interferences are handled. Finally, we apply our results to the dimensioning of a Hello protocol parameters. We propose a method to adapt the protocol parameters to meet application constraints on the neighbor discovery process and to minimize the protocol energy consumption.

  8. Network-Assisted Device-to-Device (D2D) Direct Proximity Discovery with Underlay Communication

    DEFF Research Database (Denmark)

    Pratas, Nuno; Popovski, Petar

    2015-01-01

    ) direct communication between proximate devices. While (ii) is treated extensively in the recent literature, (i) has received relatively little attention. In this paper we analyze a network-assisted underlay proximity discovery protocol, where a cellular device can take the role of: announcer (which......Device-to-Device communications are expected to play an important role in current and future cellular generations, by increasing the spatial reuse of spectrum resources and enabling lower latency communication links. This paradigm has two fundamental building blocks: (i) proximity discovery and (ii......, we consider the case where the announcers underlay their messages in the downlink transmissions that are directed towards the monitoring devices. We propose a power control scheme applied to the downlink transmission, which copes with the underlay transmission via additional power expenditure, while...

  9. Discovery Driven Growth

    DEFF Research Database (Denmark)

    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...

  10. 42 CFR 405.1037 - Discovery.

    Science.gov (United States)

    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...

  11. 20 CFR 498.207 - Discovery.

    Science.gov (United States)

    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...

  12. 42 CFR 93.512 - Discovery.

    Science.gov (United States)

    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...

  13. 42 CFR 3.516 - Discovery.

    Science.gov (United States)

    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...

  14. 29 CFR 22.21 - Discovery.

    Science.gov (United States)

    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. Impact of the discovery of radioactivity on the evolution of technologies

    International Nuclear Information System (INIS)

    Kalyazin, E.P.

    1996-01-01

    Radioactivity discovery and practical application of nuclear power gave impetus to the development of radiation technologies primarily as a by-side trend of radiation materials technology. Paper studies the place occupied by radiation technologies within the system of the modern-day production processes starting from exploration, mining, enrichment and treatment of minerals and ending with production of materials, articles and special devices. Paper shows the promising character of radiation technologies to be used for the purposes linked with the environmental protection, with power and resource savings. 41 refs., 2 figs., 1 tab

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

    International Nuclear Information System (INIS)

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

    Science.gov (United States)

    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

  18. 10 CFR 205.198 - Discovery.

    Science.gov (United States)

    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...

  19. 12 CFR 908.46 - Discovery.

    Science.gov (United States)

    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...

  20. 21 CFR 17.23 - Discovery.

    Science.gov (United States)

    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...

  1. Induced pluripotent stem cells for regenerative cardiovascular therapies and biomedical discovery.

    Science.gov (United States)

    Nsair, Ali; MacLellan, W Robb

    2011-04-30

    The discovery of induced pluripotent stem cells (iPSC) has, in the short time since their discovery, revolutionized the field of stem cell biology. This technology allows the generation of a virtually unlimited supply of cells with pluripotent potential similar to that of embryonic stem cells (ESC). However, in contrast to ESC, iPSC are not subject to the same ethical concerns and can be easily generated from living individuals. For the first time, patient-specific iPSC can be generated and offer a supply of genetically identical cells that can be differentiated into all somatic cell types for potential use in regenerative therapies or drug screening and testing. As the techniques for generation of iPSC lines are constantly evolving, new uses for human iPSC are emerging from in-vitro disease modeling to high throughput drug discovery and screening. This technology promises to revolutionize the field of medicine and offers new hope for understanding and treatment of numerous diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Computational discovery of extremal microstructure families

    Science.gov (United States)

    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

  4. Configurable User Interface Framework for Data Discovery in Cross-Disciplinary and Citizen Science

    Science.gov (United States)

    Rozell, E.; Wang, H.; West, P.; Zednik, S.; Fox, P.

    2012-04-01

    Use cases for data discovery and analysis vary widely when looking across disciplines and levels of expertise. Domain experts across disciplines may have a thorough understanding of self-describing data formats, such as netCDF, and the software packages that are compatible. However, they may be unfamiliar with specific vocabulary terms used to describe the data parameters or instrument packages in someone else's collection, which are often useful in data discovery. Citizen scientists may struggle with both expert vocabularies and knowledge of existing tools for analyzing and visualizing data. There are some solutions for each problem individually. For expert vocabularies, semantic technologies like the Resource Description Framework (RDF) have been used to map terms from an expert vocabulary to layperson terminology. For data analysis and visualization, tools can be mapped to data products using semantic technologies as well. This presentation discusses a solution to both problems based on the S2S Framework, a configurable user interface (UI) framework for Web services. S2S unifies the two solutions previously described using a data service abstraction ("search services") and a UI abstraction ("widgets"). Using the OWL Web Ontology Language, S2S defines a vocabulary for describing search services and their outputs, and the compatibility of those outputs with UI widgets. By linking search service outputs to widgets, S2S can automatically compose UIs for search and analysis of data, making it easier for citizen scientists to manipulate data. We have also created Linked Data widgets for S2S, which can leverage distributed RDF resources to present alternative views of expert vocabularies. This presentation covers some examples where we have applied these solutions to improve data discovery for both cross-disciplinary and non-expert users.

  5. Advanced electron beam techniques

    International Nuclear Information System (INIS)

    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)

  6. Linked Data: what does it offer Earth Sciences?

    Science.gov (United States)

    Cox, Simon; Schade, Sven

    2010-05-01

    interfaces, the browse metaphor, which has been such an important part of the success of the web, must be augmented with other interaction mechanisms, including query. What are the impacts on search and metadata? Hypertext provides links selected by the page provider. However, science should endeavor to be exhaustive in its use of data. Resource discovery through links must be supplemented by more systematic data discovery through search. Conversely, the crawlers that generate search indexes must be fed by resource providers (a) serving navigation pages with links to every dataset (b) adding enough 'metadata' (semantics) on each link to effectively populate the indexes. Linked Data makes this easier due to its integration with semantic web technologies, including structured vocabularies. What is the relation between structured data and Linked Data? Linked Data has focused on web-pages (primarily HTML) for human browsing, and RDF for semantics, assuming that other representations are opaque. However, this overlooks the wealth of XML data on the web, some of which is structured according to XML Schemas that provide semantics. Technical applications can use content-negotiation to get a structured representation, and exploit its semantics. Particularly relevant for earth sciences are data representations based on OGC Geography Markup Language (GML), such as GeoSciML, O&M and MOLES. GML was strongly influenced by RDF, and typed links are intrinsic: xlink:href plays the role that rdf:resource does in RDF representations. Services which expose GML-formatted resources (such as OGC Web Feature Service) are a prototype of Linked Data. Giving credit where it is due. Organizations investing in data collection may be reluctant to publish the raw data prior to completing an initial analysis. To encourage early data publication the system must provide suitable incentives, and citation analysis must recognize the increasing diversity of publication routes and forms. Linked Data makes it

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

    Science.gov (United States)

    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

  8. The circumstances of minor planet discovery

    International Nuclear Information System (INIS)

    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

  9. Missing Links in Genes to Traits: Toward Teaching for an Integrated Framework of Genetics

    Science.gov (United States)

    Pavlova, Iglika V.; Kreher, Scott A.

    2013-01-01

    Genetics, one of the most influential fields, underlies all of biology and produces discoveries that are in the news daily. However, many students leave introductory biology and genetics courses lacking a coherent framework of knowledge to use in their daily lives. We identify substantial "missing links" in the teaching of foundational…

  10. The discovery, development and future of GMR: The Nobel Prize 2007

    International Nuclear Information System (INIS)

    Thompson, Sarah M

    2008-01-01

    One hundred and one years after J J Thomson was awarded the Nobel Prize for the discovery of the electron, the 2007 Nobel Prize for Physics was awarded to Professors Peter Gruenberg and Albert Fert for the discovery of giant magnetoresistance (GMR) in which the spin as well as the charge of the electron is manipulated and exploited in nanoscale magnetic materials. The journey to GMR started with Lord Kelvin who 150 years ago in 1857 made the first observations of anisotropic magnetoresistance and includes Sir Neville Mott who in 1936 realized that electric current in metals could be considered as two independent spin channels. Modern technology also has a significant role to play in the award of this Nobel Prize: GMR is only manifest in nanoscale materials, and the development of nanotechnology growth techniques was a necessary pre-requisite; further, the considerable demands of the magnetic data storage industry to drive up the data density stored on a hard disk fuelled an enormous international research effort following the initial discovery with the result that more than 5 billion GMR read heads have been manufactured since 1997, ubiquitous in hard disks today. This technology drive continues to inspire exploration of the spin current in the field now known as spintronics, generating new ideas and applications. This review explores the science underpinning GMR and spintronics, the different routes to its discovery taken by Professors Gruenberg and Fert, the new science, materials and applications that the discovery has triggered and the considerable potential for the future. (topical review)

  11. The discovery, development and future of GMR: The Nobel Prize 2007

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Sarah M [Department of Physics, University of York, York, YO10 5DD (United Kingdom)

    2008-05-07

    One hundred and one years after J J Thomson was awarded the Nobel Prize for the discovery of the electron, the 2007 Nobel Prize for Physics was awarded to Professors Peter Gruenberg and Albert Fert for the discovery of giant magnetoresistance (GMR) in which the spin as well as the charge of the electron is manipulated and exploited in nanoscale magnetic materials. The journey to GMR started with Lord Kelvin who 150 years ago in 1857 made the first observations of anisotropic magnetoresistance and includes Sir Neville Mott who in 1936 realized that electric current in metals could be considered as two independent spin channels. Modern technology also has a significant role to play in the award of this Nobel Prize: GMR is only manifest in nanoscale materials, and the development of nanotechnology growth techniques was a necessary pre-requisite; further, the considerable demands of the magnetic data storage industry to drive up the data density stored on a hard disk fuelled an enormous international research effort following the initial discovery with the result that more than 5 billion GMR read heads have been manufactured since 1997, ubiquitous in hard disks today. This technology drive continues to inspire exploration of the spin current in the field now known as spintronics, generating new ideas and applications. This review explores the science underpinning GMR and spintronics, the different routes to its discovery taken by Professors Gruenberg and Fert, the new science, materials and applications that the discovery has triggered and the considerable potential for the future. (topical review)

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

    Science.gov (United States)

    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. PENGARUH PENGGUNAAN METODE DISCOVERY BERBASIS MEDIA REALITA TERHADAP HASIL BELAJAR MATAKULIAH KONSEP DASAR IPA 1

    Directory of Open Access Journals (Sweden)

    Idam Ragil Widianto Atmojo

    2015-10-01

    Full Text Available This study aims to determine how much influence the use of media-based discovery method's realities of the learning outcomes during the course Basic Concepts IPA 1 when compared to those taught using direct instruction-based Power Point (PPT. This research is a quantitative type of experiment using a quasi-experimental method (Quasi-Experimental Design. Experimental Design. Design research is the Control Group Pre-test Post-test. Populations of this study were all students of PGSD FKIP UNS second semester of academic year 2013/2014. Cluster Random Sampling is used in sampling. The technique of collecting data through observation, documentation, and testing. The data analysis technique used is the prerequisite test data analysis and hypothesis testing. For prerequisite test, including normality test with chip-square method and homogeneity test methods Bartlett. Based on the analysis of t test showed the t count> t table (3.599> 2.001, so that H0 is rejected. Thus there is a positive impact on learning outcomes of the course the basic concepts of science one-second semester students are taught using methods of discovery-based media reality. Conclusions This study is the result of learning the basic concepts of science subject 1 student taught by media-based discovery method's realities better than students taught by direct instruction-based power point. Keywords: discovery, media reality, learning outcomes, basic concepts IPA.

  14. Top partner discovery in the T→tZ channel at the LHC

    International Nuclear Information System (INIS)

    Reuter, Juergen; Tonini, Marco

    2014-09-01

    In this paper we study the discovery potential of the LHC run II for heavy vector-like top quarks in the decay channel to a top and a Z boson. Despite the usually smaller branching ratio compared to charged-current decays this channel is rather clean and allows a complete mass reconstruction of the heavy top. The latter is achieved in the fully hadronic top channel using boosted jet and jet substructure techniques. To be as model-independent as possible, a simplified model approach with only two free parameters has been applied. The results are presented in terms of parameter space regions for 3σ evidence or 5σ discovery for such new states in that channel.

  15. Toxins and drug discovery.

    Science.gov (United States)

    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.

  16. QSAR studies in the discovery of novel type-II diabetic therapies.

    Science.gov (United States)

    Abuhammad, Areej; Taha, Mutasem O

    2016-01-01

    Type-II diabetes mellitus (T2DM) is a complex chronic disease that represents a major therapeutic challenge. Despite extensive efforts in T2DM drug development, therapies remain unsatisfactory. Currently, there are many novel and important antidiabetic drug targets under investigation by many research groups worldwide. One of the main challenges to develop effective orally active hypoglycemic agents is off-target effects. Computational tools have impacted drug discovery at many levels. One of the earliest methods is quantitative structure-activity relationship (QSAR) studies. QSAR strategies help medicinal chemists understand the relationship between hypoglycemic activity and molecular properties. Hence, QSAR may hold promise in guiding the synthesis of specifically designed novel ligands that demonstrate high potency and target selectivity. This review aims to provide an overview of the QSAR strategies used to model antidiabetic agents. In particular, this review focuses on drug targets that raised recent scientific interest and/or led to successful antidiabetic agents in the market. Special emphasis has been made on studies that led to the identification of novel antidiabetic scaffolds. Computer-aided molecular design and discovery techniques like QSAR have a great potential in designing leads against complex diseases such as T2DM. Combined with other in silico techniques, QSAR can provide more useful and rational insights to facilitate the discovery of novel compounds. However, since T2DM is a complex disease that includes several faulty biological targets, multi-target QSAR studies are recommended in the future to achieve efficient antidiabetic therapies.

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

    International Nuclear Information System (INIS)

    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.)

  18. mHealth Visual Discovery Dashboard.

    Science.gov (United States)

    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.

  19. Use of Persistent Identifiers to link Heterogeneous Data Systems in the Integrated Earth Data Applications (IEDA) Facility

    Science.gov (United States)

    Hsu, L.; Lehnert, K. A.; Carbotte, S. M.; Arko, R. A.; Ferrini, V.; O'hara, S. H.; Walker, J. D.

    2012-12-01

    The Integrated Earth Data Applications (IEDA) facility maintains multiple data systems with a wide range of solid earth data types from the marine, terrestrial, and polar environments. Examples of the different data types include syntheses of ultra-high resolution seafloor bathymetry collected on large collaborative cruises and analytical geochemistry measurements collected by single investigators in small, unique projects. These different data types have historically been channeled into separate, discipline-specific databases with search and retrieval tailored for the specific data type. However, a current major goal is to integrate data from different systems to allow interdisciplinary data discovery and scientific analysis. To increase discovery and access across these heterogeneous systems, IEDA employs several unique IDs, including sample IDs (International Geo Sample Number, IGSN), person IDs (GeoPass ID), funding award IDs (NSF Award Number), cruise IDs (from the Marine Geoscience Data System Expedition Metadata Catalog), dataset IDs (DOIs), and publication IDs (DOIs). These IDs allow linking of a sample registry (System for Earth SAmple Registration), data libraries and repositories (e.g. Geochemical Research Library, Marine Geoscience Data System), integrated synthesis databases (e.g. EarthChem Portal, PetDB), and investigator services (IEDA Data Compliance Tool). The linked systems allow efficient discovery of related data across different levels of granularity. In addition, IEDA data systems maintain links with several external data systems, including digital journal publishers. Links have been established between the EarthChem Portal and ScienceDirect through publication DOIs, returning sample-level objects and geochemical analyses for a particular publication. Linking IEDA-hosted data to digital publications with IGSNs at the sample level and with IEDA-allocated dataset DOIs are under development. As an example, an individual investigator could sign up

  20. Service discovery at home

    NARCIS (Netherlands)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  2. The Greatest Mathematical Discovery?

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Improving local clustering based top-L link prediction methods via asymmetric link clustering information

    Science.gov (United States)

    Wu, Zhihao; Lin, Youfang; Zhao, Yiji; Yan, Hongyan

    2018-02-01

    Networks can represent a wide range of complex systems, such as social, biological and technological systems. Link prediction is one of the most important problems in network analysis, and has attracted much research interest recently. Many link prediction methods have been proposed to solve this problem with various techniques. We can note that clustering information plays an important role in solving the link prediction problem. In previous literatures, we find node clustering coefficient appears frequently in many link prediction methods. However, node clustering coefficient is limited to describe the role of a common-neighbor in different local networks, because it cannot distinguish different clustering abilities of a node to different node pairs. In this paper, we shift our focus from nodes to links, and propose the concept of asymmetric link clustering (ALC) coefficient. Further, we improve three node clustering based link prediction methods via the concept of ALC. The experimental results demonstrate that ALC-based methods outperform node clustering based methods, especially achieving remarkable improvements on food web, hamster friendship and Internet networks. Besides, comparing with other methods, the performance of ALC-based methods are very stable in both globalized and personalized top-L link prediction tasks.

  4. Open Drug Discovery Toolkit (ODDT): a new open-source player in the drug discovery field.

    Science.gov (United States)

    Wójcikowski, Maciej; Zielenkiewicz, Piotr; Siedlecki, Pawel

    2015-01-01

    There has been huge progress in the open cheminformatics field in both methods and software development. Unfortunately, there has been little effort to unite those methods and software into one package. We here describe the Open Drug Discovery Toolkit (ODDT), which aims to fulfill the need for comprehensive and open source drug discovery software. The Open Drug Discovery Toolkit was developed as a free and open source tool for both computer aided drug discovery (CADD) developers and researchers. ODDT reimplements many state-of-the-art methods, such as machine learning scoring functions (RF-Score and NNScore) and wraps other external software to ease the process of developing CADD pipelines. ODDT is an out-of-the-box solution designed to be easily customizable and extensible. Therefore, users are strongly encouraged to extend it and develop new methods. We here present three use cases for ODDT in common tasks in computer-aided drug discovery. Open Drug Discovery Toolkit is released on a permissive 3-clause BSD license for both academic and industrial use. ODDT's source code, additional examples and documentation are available on GitHub (https://github.com/oddt/oddt).

  5. The in silico drug discovery toolbox: applications in lead discovery and optimization.

    Science.gov (United States)

    Bruno, Agostino; Costantino, Gabriele; Sartori, Luca; Radi, Marco

    2017-11-06

    Discovery and development of a new drug is a long lasting and expensive journey that takes around 15 years from starting idea to approval and marketing of new medication. Despite the R&D expenditures have been constantly increasing in the last few years, number of new drugs introduced into market has been steadily declining. This is mainly due to preclinical and clinical safety issues, which still represent about 40% of drug discontinuation. From this point of view, it is clear that if we want to increase drug-discovery success rate and reduce costs associated with development of a new drug, a comprehensive evaluation/prediction of potential safety issues should be conducted as soon as possible during early drug discovery phase. In the present review, we will analyse the early steps of drug-discovery pipeline, describing the sequence of steps from disease selection to lead optimization and focusing on the most common in silico tools used to assess attrition risks and build a mitigation plan. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Academic Drug Discovery Centres

    DEFF Research Database (Denmark)

    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...

  7. Service Discovery At Home

    NARCIS (Netherlands)

    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

  8. Synthetic biology of antimicrobial discovery.

    Science.gov (United States)

    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.

  9. Fragment-based drug discovery using rational design.

    Science.gov (United States)

    Jhoti, H

    2007-01-01

    Fragment-based drug discovery (FBDD) is established as an alternative approach to high-throughput screening for generating novel small molecule drug candidates. In FBDD, relatively small libraries of low molecular weight compounds (or fragments) are screened using sensitive biophysical techniques to detect their binding to the target protein. A lower absolute affinity of binding is expected from fragments, compared to much higher molecular weight hits detected by high-throughput screening, due to their reduced size and complexity. Through the use of iterative cycles of medicinal chemistry, ideally guided by three-dimensional structural data, it is often then relatively straightforward to optimize these weak binding fragment hits into potent and selective lead compounds. As with most other lead discovery methods there are two key components of FBDD; the detection technology and the compound library. In this review I outline the two main approaches used for detecting the binding of low affinity fragments and also some of the key principles that are used to generate a fragment library. In addition, I describe an example of how FBDD has led to the generation of a drug candidate that is now being tested in clinical trials for the treatment of cancer.

  10. Networked Airborne Communications Using Adaptive Multi Beam Directional Links

    Science.gov (United States)

    2016-03-05

    Networked Airborne Communications Using Adaptive Multi-Beam Directional Links R. Bruce MacLeod Member, IEEE, and Adam Margetts Member, IEEE MIT...provide new techniques for increasing throughput in airborne adaptive directional net- works. By adaptive directional linking, we mean systems that can...techniques can dramatically increase the capacity in airborne networks. Advances in digital array technology are beginning to put these gains within reach

  11. Discovery Mondays - “Relativity Theory... strange! Did you say strange?”

    CERN Multimedia

    2005-01-01

    We all know that famous equation E=mc2, but do you know its true significance? Relativity theory: what is the meaning of this strange concept which plunged the physics world into turmoil 100 years ago? What effects can be observed today? Did you know that the GPS system would not work if relativity was not taken into account? The next Discovery Monday will take you on a journey into a strange world. You will be able to witness for yourselves the consequences of Einstein's theories. How, for example, can relativity theory be tested by eclipses? What consequences does it have for the accelerators at CERN? How can it be used to measure the mass of enormous black holes? And finally, how is it linked to the puzzle surrounding the missing mass of the Universe? As part of the World Year of Physics, the next Discovery Monday will be dedicated to one of the theories that Einstein published in 1905, his “annus mirabilis”. Join us at the Microcosm (Reception Building 33, Meyrin site), on Monday 5th September ...

  12. Discovery Mondays - “Relativity Theory... strange! Did you say strange?”

    CERN Multimedia

    2005-01-01

    We all know that famous equation E=mc2, but do you know its true significance? Relativity theory: what is the meaning of this strange concept which plunged the physics world into turmoil 100 years ago? What effects can be observed today? Did you know that the GPS system would not work if relativity was not taken into account? The next Discovery Monday will take you on a journey into a strange world. You will be able to witness for yourselves the consequences of Einstein's theories. How, for example, can relativity theory be tested by eclipses? What consequences does it have for the accelerators at CERN? How can it be used to measure the mass of enormous black holes? And finally, how is it linked to the puzzle surrounding the missing mass of the Universe? As part of the World Year of Physics, the next Discovery Monday will be dedicated to one of the theories that Einstein published in 1905, his “annus mirabilis”. Join us at the Microcosm (Reception Building 33, Meyrin site), on Monday 5th Septemb...

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

    International Nuclear Information System (INIS)

    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

  14. Simulated drug discovery process to conduct a synoptic assessment of pharmacy students.

    Science.gov (United States)

    Richardson, Alan; Curtis, Anthony D M; Moss, Gary P; Pearson, Russell J; White, Simon; Rutten, Frank J M; Perumal, Dhaya; Maddock, Katie

    2014-03-12

    OBJECTIVE. To implement and assess a task-based learning exercise that prompts pharmacy students to integrate their understanding of different disciplines. DESIGN. Master of pharmacy (MPharm degree) students were provided with simulated information from several preclinical science and from clinical trials and asked to synthesize this into a marketing authorization application for a new drug. Students made a link to pharmacy practice by creating an advice leaflet for pharmacists. ASSESSMENT. Students' ability to integrate information from different disciplines was evaluated by oral examination. In 2 successive academic years, 96% and 82% of students demonstrated an integrated understanding of their proposed new drug. Students indicated in a survey that their understanding of the links between different subjects improved. CONCLUSION. Simulated drug discovery provides a learning environment that emphasizes the connectivity of the preclinical sciences with each other and the practice of pharmacy.

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

    Science.gov (United States)

    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."

  16. Summary of the BioLINK SIG 2013 meeting at ISMB/ECCB 2013.

    Science.gov (United States)

    Verspoor, Karin; Shatkay, Hagit; Hirschman, Lynette; Blaschke, Christian; Valencia, Alfonso

    2015-01-15

    The ISMB Special Interest Group on Linking Literature, Information and Knowledge for Biology (BioLINK) organized a one-day workshop at ISMB/ECCB 2013 in Berlin, Germany. The theme of the workshop was 'Roles for text mining in biomedical knowledge discovery and translational medicine'. This summary reviews the outcomes of the workshop. Meeting themes included concept annotation methods and applications, extraction of biological relationships and the use of text-mined data for biological data analysis. All articles are available at http://biolinksig.org/proceedings-online/. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

    CERN Document Server

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  19. The discovery of radioactivity: the centenary

    International Nuclear Information System (INIS)

    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

  20. The π discovery

    International Nuclear Information System (INIS)

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Synthetic biology of antimicrobial discovery

    Science.gov (United States)

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

    Science.gov (United States)

    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.

  4. Dewey linked data: Making connections with old friends and new acquaintances

    Directory of Open Access Journals (Sweden)

    Joan S. Mitchell

    2013-01-01

    Full Text Available This paper explores the history, uses cases, and future plans associated with availability of the Dewey Decimal Classification (DDC system as linked data. Parts of DDC system have been available as linked data since 2009. Initial efforts included the DDC Summaries  in eleven languages exposed as linked data in dewey.info. In 2010, the content of dewey.info was further extended by the addition of assignable numbers and captions from the Abridged Edition 14 data files in English, Italian, and Vietnamese. During 2012, we will add assignable numbers and captions from the latest full edition database, DDC 23. In addition to the “old friends” of different Dewey language versions, institutions such as the British Library and Deutsche Nationalbibliothek have made use of Dewey linked data in bibliographic records and authority files, and AGROVOC has linked to our data at a general level. We expect to extend our linked data network shortly to “new acquaintances” such as GeoNames, ISO 639-3 language codes, and Mathematics Subject Classification. In particular, the paper examines the linking process to GeoNames as an example of cross-domain vocabulary alignment. In addition to linking plans, the paper reports on use cases that facilitate machine-assisted categorization and support discovery in the semantic web environment.

  5. 'The Lusiads', poem of discovery

    Directory of Open Access Journals (Sweden)

    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”.

  6. Computational methods in drug discovery

    OpenAIRE

    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...

  7. Choosing Discovery: A Literature Review on the Selection and Evaluation of Discovery Layers

    Science.gov (United States)

    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…

  8. Investigations into Library Web-Scale Discovery Services

    Directory of Open Access Journals (Sweden)

    Jason Vaughan

    2008-03-01

    Full Text Available Web-scale discovery services for libraries provide deep discovery to a library’s local and licensed content, and represent an evolution, perhaps a revolution, for end user information discovery as pertains to library collections.  This article frames the topic of web-scale discovery, and begins by illuminating web-scale discovery from an academic library’s perspective – that is, the internal perspective seeking widespread staff participation in the discovery conversation.  This included the creation of a discovery task force, a group which educated library staff, conducted internal staff surveys, and gathered observations from early adopters.  The article next addresses the substantial research conducted with library vendors which have developed these services.  Such work included drafting of multiple comprehensive question lists distributed to the vendors, onsite vendor visits, and continual tracking of service enhancements.  Together, feedback gained from library staff, insights arrived at by the Discovery Task Force, and information gathered from vendors collectively informed the recommendation of a service for the UNLV Libraries.

  9. The Europa Ocean Discovery mission

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. 29 CFR 18.13 - Discovery methods.

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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.

  12. Parameter discovery in stochastic biological models using simulated annealing and statistical model checking.

    Science.gov (United States)

    Hussain, Faraz; Jha, Sumit K; Jha, Susmit; Langmead, Christopher J

    2014-01-01

    Stochastic models are increasingly used to study the behaviour of biochemical systems. While the structure of such models is often readily available from first principles, unknown quantitative features of the model are incorporated into the model as parameters. Algorithmic discovery of parameter values from experimentally observed facts remains a challenge for the computational systems biology community. We present a new parameter discovery algorithm that uses simulated annealing, sequential hypothesis testing, and statistical model checking to learn the parameters in a stochastic model. We apply our technique to a model of glucose and insulin metabolism used for in-silico validation of artificial pancreata and demonstrate its effectiveness by developing parallel CUDA-based implementation for parameter synthesis in this model.

  13. From the endometrium physiology to a comprehensive strategy for the discovery of ovarian cancer biomarkers

    OpenAIRE

    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...

  14. 41 CFR 60-30.33 - Discovery.

    Science.gov (United States)

    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...

  15. A novel strategy for preparing mechanically robust ionically cross-linked alginate hydrogels

    International Nuclear Information System (INIS)

    Jejurikar, Aparna; Lawrie, Gwen; Groendahl, Lisbeth; Martin, Darren

    2011-01-01

    The properties of alginate films modified using two cross-linker ions (Ca 2+ and Ba 2+ ), comparing two separate cross-linking techniques (the traditional immersion (IM) method and a new strategy in a pressure-assisted diffusion (PD) method), are evaluated. This was achieved through measuring metal ion content, water uptake and film stability in an ionic solution ([Ca 2+ ] = 2 mM). Characterization of the internal structure and mechanical properties of hydrated films were established by cryogenic scanning electron microscopy and tensile testing, respectively. It was found that gels formed by the PD technique possessed greater stability and did not exhibit any delamination after 21 day immersion as compared to gels formed by the IM technique. The Ba 2+ cross-linked gels possessed significantly higher cross-linking density as reflected in lower water content, a more dense internal structure and higher Young's modulus compared to Ca 2+ cross-linked gels. For the Ca 2+ cross-linked gels, a large improvement in the mechanical properties was observed in gels produced by the PD technique and this was attributed to thicker pore walls observed within the hydrogel structure. In contrast, for the Ba 2+ cross-linked gels, the PD technique resulted in gels that had lower tensile strength and strain energy density and this was attributed to phase separation and larger macropores in this gel.

  16. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    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...

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

    DEFF Research Database (Denmark)

    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...

  18. 45 CFR 213.23a - Discovery.

    Science.gov (United States)

    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...

  19. Coding/modulation trade-offs for Shuttle wideband data links

    Science.gov (United States)

    Batson, B. H.; Huth, G. K.; Trumpis, B. D.

    1974-01-01

    This paper describes various modulation and coding schemes which are potentially applicable to the Shuttle wideband data relay communications link. This link will be capable of accommodating up to 50 Mbps of scientific data and will be subject to a power constraint which forces the use of channel coding. Although convolutionally encoded coherent binary PSK is the tentative signal design choice for the wideband data relay link, FM techniques are of interest because of the associated hardware simplicity and because an FM system is already planned to be available for transmission of television via relay satellite to the ground. Binary and M-ary FSK are considered as candidate modulation techniques, and both coherent and noncoherent ground station detection schemes are examined. The potential use of convolutional coding is considered in conjunction with each of the candidate modulation techniques.

  20. Effectiveness of link prediction for face-to-face behavioral networks.

    Science.gov (United States)

    Tsugawa, Sho; Ohsaki, Hiroyuki

    2013-01-01

    Research on link prediction for social networks has been actively pursued. In link prediction for a given social network obtained from time-windowed observation, new link formation in the network is predicted from the topology of the obtained network. In contrast, recent advances in sensing technology have made it possible to obtain face-to-face behavioral networks, which are social networks representing face-to-face interactions among people. However, the effectiveness of link prediction techniques for face-to-face behavioral networks has not yet been explored in depth. To clarify this point, here we investigate the accuracy of conventional link prediction techniques for networks obtained from the history of face-to-face interactions among participants at an academic conference. Our findings were (1) that conventional link prediction techniques predict new link formation with a precision of 0.30-0.45 and a recall of 0.10-0.20, (2) that prolonged observation of social networks often degrades the prediction accuracy, (3) that the proposed decaying weight method leads to higher prediction accuracy than can be achieved by observing all records of communication and simply using them unmodified, and (4) that the prediction accuracy for face-to-face behavioral networks is relatively high compared to that for non-social networks, but not as high as for other types of social networks.

  1. Knowledge Representation and Management: a Linked Data Perspective.

    Science.gov (United States)

    Barros, M; Couto, F M

    2016-11-10

    Biomedical research is increasingly becoming a data-intensive science in several areas, where prodigious amounts of data is being generated that has to be stored, integrated, shared and analyzed. In an effort to improve the accessibility of data and knowledge, the Linked Data initiative proposed a well-defined set of recommendations for exposing, sharing and integrating data, information and knowledge, using semantic web technologies. The main goal of this paper is to identify the current status and future trends of knowledge representation and management in Life and Health Sciences, mostly with regard to linked data technologies. We selected three prominent linked data studies, namely Bio2RDF, Open PHACTS and EBI RDF platform, and selected 14 studies published after 2014 (inclusive) that cited any of the three studies. We manually analyzed these 14 papers in relation to how they use linked data techniques. The analyses show a tendency to use linked data techniques in Life and Health Sciences, and even if some studies do not follow all of the recommendations, many of them already represent and manage their knowledge using RDF and biomedical ontologies. These insights from RDF and biomedical ontologies are having a strong impact on how knowledge is generated from biomedical data, by making data elements increasingly connected and by providing a better description of their semantics. As health institutes become more data centric, we believe that the adoption of linked data techniques will continue to grow and be an effective solution to knowledge representation and management.

  2. Link Prediction in Social Networks: the State-of-the-Art

    OpenAIRE

    Wang, Peng; Xu, Baowen; Wu, Yurong; Zhou, Xiaoyu

    2014-01-01

    In social networks, link prediction predicts missing links in current networks and new or dissolution links in future networks, is important for mining and analyzing the evolution of social networks. In the past decade, many works have been done about the link prediction in social networks. The goal of this paper is to comprehensively review, analyze and discuss the state-of-the-art of the link prediction in social networks. A systematical category for link prediction techniques and problems ...

  3. The linked medical data access control framework.

    Science.gov (United States)

    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.

  4. Plasma biomarker discovery in preeclampsia using a novel differential isolation technology for circulating extracellular vesicles.

    Science.gov (United States)

    Tan, Kok Hian; Tan, Soon Sim; Sze, Siu Kwan; Lee, Wai Kheong Ryan; Ng, Mor Jack; Lim, Sai Kiang

    2014-10-01

    To circumvent the complex protein milieu of plasma and discover robust predictive biomarkers for preeclampsia (PE), we investigate if phospholipid-binding ligands can reduce the milieu complexity by extracting plasma extracellular vesicles for biomarker discovery. Cholera toxin B chain (CTB) and annexin V (AV) which respectively binds GM1 ganglioside and phosphatidylserine were used to isolate extracellular vesicles from plasma of PE patients and healthy pregnant women. The proteins in the vesicles were identified using enzyme-linked immunosorbent assay, antibody array, and mass spectrometry. CTB and AV were found to bind 2 distinct groups of extracellular vesicles. Antibody array and enzyme-linked immunosorbent assay revealed that PE patients had elevated levels of CD105, interleukin-6, placental growth factor, tissue inhibitor of metallopeptidase 1, and atrial natriuretic peptide in cholera toxin B- but not AV-vesicles, and elevated levels of plasminogen activator inhibitor-1, pro-calcitonin, S100b, tumor growth factor β, vascular endothelial growth factor receptor 1, brain natriuretic peptide, and placental growth factor in both cholera toxin B- and AV-vesicles. CD9 level was elevated in cholera toxin B-vesicles but reduced in AV vesicles of PE patients. Proteome analysis revealed that in cholera toxin B-vesicles, 87 and 222 proteins were present only in PE patients and healthy pregnant women respectively while in AV-vesicles, 104 and 157 proteins were present only in PE and healthy pregnant women, respectively. This study demonstrated for the first time that CTB and AV bind unique extracellular vesicles, and their protein cargo reflects the disease state of the patient. The successful use of these 2 ligands to isolate circulating plasma extracellular vesicles for biomarker discovery in PE represents a novel technology for biomarker discovery that can be applied to other specialties. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. PERFORMANCE EVALUATION OF AN ALTERNATIVE CONTROLLER FOR BLUETOOTH SERVICE DISCOVERY

    Directory of Open Access Journals (Sweden)

    M. Sughasiny

    2012-06-01

    Full Text Available Bluetooth is a short range radio technology to form a small wireless system. It is used in low –cost, low power ad-hoc networks and it suffers from long service discovery delay and high power consumption. Bluetooth employs the 2.4 GHz ISM band, sharing the same bandwidth with the wireless LAN implementing the IEEE 802.11 standards. Thus it causes significantly lower interference. For improving the efficiency of SDP, we present an implementation of Bluetooth 2.1 in the NS-2 simulator, discuss the IEEE 802.11b as a Bluetooth controller and propose a new alternative Bluetooth Controller based on Adaptive Frequency Hopping techniques using Amplifier Power. The resulting approach significantly reduces the service discovery time, thereby lowering power consumption and increasing the throughput. We present the benefits of our new approach and compare it with existing approach using NS-2 Simulations and we have presented the comparison graphs in support of our approach.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Sassatelli, Giuseppe

    2011-10-01

    Full Text Available 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 to the foundation of the "Museo Civico Archeologico" (Civic Archaeological Museum, known as a major achievement in the city's history, which is aimed at defining and recovering an urban identity according to the the project of national unity.

  8. Discovery of massive neutral vector mesons

    International Nuclear Information System (INIS)

    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

  9. Functional principles of registry-based service discovery

    NARCIS (Netherlands)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. Materials Discovery | Materials Science | NREL

    Science.gov (United States)

    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

  12. On the pulse of discovery

    Science.gov (United States)

    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.

  13. Current status and future prospects for enabling chemistry technology in the drug discovery process [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    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.

  14. Discovery Mondays: Transporting tonnes of equipment with millimetre precision

    CERN Multimedia

    2005-01-01

    Transporting huge, very heavy but also frequently fragile items at CERN often presents a real challenge. The task becomes even more challenging when it involves lowering huge LHC machine and detector components 100 metres below ground. The Laboratory's Transport Service uses various techniques and different types of transport and heavy handling equipment to perform these delicate operations. You will have an opportunity to find out more about how they do their job at the next Discovery Monday event. You will have a close encounter with the trailer used to transport the impressive 15 metre-long, 35-tonne dipole magnets. You will be able to install mock-up magnets in a beam line or test your skill using heavy handling equipment to carry out a most unusual fishing operation. You will be able to take a trip in a three-metre-high lorry and have a once-in-a-lifetime opportunity to operate a crane. You will also be able to take a test drive in the famous roll-over simulator vehicle. At the coming Discovery Monday...

  15. Discovery radiomics via evolutionary deep radiomic sequencer discovery for pathologically proven lung cancer detection.

    Science.gov (United States)

    Shafiee, Mohammad Javad; Chung, Audrey G; Khalvati, Farzad; Haider, Masoom A; Wong, Alexander

    2017-10-01

    While lung cancer is the second most diagnosed form of cancer in men and women, a sufficiently early diagnosis can be pivotal in patient survival rates. Imaging-based, or radiomics-driven, detection methods have been developed to aid diagnosticians, but largely rely on hand-crafted features that may not fully encapsulate the differences between cancerous and healthy tissue. Recently, the concept of discovery radiomics was introduced, where custom abstract features are discovered from readily available imaging data. We propose an evolutionary deep radiomic sequencer discovery approach based on evolutionary deep intelligence. Motivated by patient privacy concerns and the idea of operational artificial intelligence, the evolutionary deep radiomic sequencer discovery approach organically evolves increasingly more efficient deep radiomic sequencers that produce significantly more compact yet similarly descriptive radiomic sequences over multiple generations. As a result, this framework improves operational efficiency and enables diagnosis to be run locally at the radiologist's computer while maintaining detection accuracy. We evaluated the evolved deep radiomic sequencer (EDRS) discovered via the proposed evolutionary deep radiomic sequencer discovery framework against state-of-the-art radiomics-driven and discovery radiomics methods using clinical lung CT data with pathologically proven diagnostic data from the LIDC-IDRI dataset. The EDRS shows improved sensitivity (93.42%), specificity (82.39%), and diagnostic accuracy (88.78%) relative to previous radiomics approaches.

  16. Fade Mitigation Techniques at Ka-Band

    Science.gov (United States)

    Dissanayake, Asoka (Editor)

    1996-01-01

    Rain fading is the dominant propagation impairment affecting Ka-band satellite links and rain fade mitigation is a key element in the design of Ka-band satellite networks. Some of the common fade mitigation techniques include: power control, diversity, adaptive coding, and resource sharing. The Advanced Communications Technology Satellite (ACTS) provides an excellent opportunity to develop and test Ka-band rain impairment amelioration techniques. Up-link power control and diversity are discussed in this paper.

  17. Discovery of inhibitors of bacterial histidine kinases

    NARCIS (Netherlands)

    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

  18. Analysis of powered two-wheeler crashes in Italy by classification trees and rules discovery.

    Science.gov (United States)

    Montella, Alfonso; Aria, Massimo; D'Ambrosio, Antonio; Mauriello, Filomena

    2012-11-01

    Aim of the study was the analysis of powered two-wheeler (PTW) crashes in Italy in order to detect interdependence as well as dissimilarities among crash characteristics and provide insights for the development of safety improvement strategies focused on PTWs. At this aim, data mining techniques were used to analyze the data relative to the 254,575 crashes involving PTWs occurred in Italy in the period 2006-2008. Classification trees analysis and rules discovery were performed. Tree-based methods are non-linear and non-parametric data mining tools for supervised classification and regression problems. They do not require a priori probabilistic knowledge about the phenomena under studying and consider conditional interactions among input data. Rules discovery is the identification of sets of items (i.e., crash patterns) that occur together in a given event (i.e., a crash in our study) more often than they would if they were independent of each other. Thus, the method can detect interdependence among crash characteristics. Due to the large number of patterns considered, both methods suffer from an extreme risk of finding patterns that appear due to chance alone. To overcome this problem, in our study we randomly split the sample data in two data sets and used well-established statistical practices to evaluate the statistical significance of the results. Both the classification trees and the rules discovery were effective in providing meaningful insights about PTW crash characteristics and their interdependencies. Even though in several cases different crash characteristics were highlighted, the results of the two the analysis methods were never contradictory. Furthermore, most of the findings of this study were consistent with the results of previous studies which used different analytical techniques, such as probabilistic models of crash injury severity. Basing on the analysis results, engineering countermeasures and policy initiatives to reduce PTW injuries and

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  1. Service discovery using Bloom filters

    NARCIS (Netherlands)

    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

  2. Collagen cross-linking in thin corneas

    Directory of Open Access Journals (Sweden)

    Prema Padmanabhan

    2013-01-01

    Full Text Available Collagen cross-linking (CXL has become the standard of care for progressive keratoconus, after numerous clinical studies have established its efficacy and safety in suitably selected eyes. The standard protocol is applicable in eyes which have a minimum corneal thickness of 400 μm after epithelial debridement. This prerequisite was stipulated to protect the corneal endothelium and intraocular tissues from the deleterious effect of ultraviolet-A (UVA radiation. However, patients with keratoconus often present with corneal thickness of less than 400 μm and could have otherwise benefited from this procedure. A few modifications of the standard procedure have been suggested to benefit these patients without a compromise in safety. Transepithelial cross-linking, pachymetry-guided epithelial debridement before cross-linking, and the use of hypoosmolar riboflavin are some of the techniques that have been attempted. Although clinical data is limited at the present time, these techniques are worth considering in patients with thin corneas. Further studies are needed to scientifically establish their efficacy and safety.

  3. A scientometric prediction of the discovery of the first potentially habitable planet with a mass similar to Earth.

    Science.gov (United States)

    Arbesman, Samuel; Laughlin, Gregory

    2010-10-04

    The search for a habitable extrasolar planet has long interested scientists, but only recently have the tools become available to search for such planets. In the past decades, the number of known extrasolar planets has ballooned into the hundreds, and with it, the expectation that the discovery of the first Earth-like extrasolar planet is not far off. Here, we develop a novel metric of habitability for discovered planets and use this to arrive at a prediction for when the first habitable planet will be discovered. Using a bootstrap analysis of currently discovered exoplanets, we predict the discovery of the first Earth-like planet to be announced in the first half of 2011, with the likeliest date being early May 2011. Our predictions, using only the properties of previously discovered exoplanets, accord well with external estimates for the discovery of the first potentially habitable extrasolar planet and highlight the the usefulness of predictive scientometric techniques to understand the pace of scientific discovery in many fields.

  4. Using concepts in literature-based discovery : Simulating Swanson's Raynaud-fish oil and migraine-magnesium discoveries

    NARCIS (Netherlands)

    Weeber, M; Klein, Henny; de Jong-van den Berg, LTW; Vos, R

    Literature-based discovery has resulted in new knowledge. In the biomedical context, Don R. Swanson has generated several literature-based hypotheses that have been corroborated experimentally and clinically. In this paper, we propose a two-step model of the discovery process in which hypotheses are

  5. 12 CFR 747.24 - Scope of document discovery.

    Science.gov (United States)

    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...

  6. Resource Discovery in Activity-Based Sensor Networks

    DEFF Research Database (Denmark)

    Bucur, Doina; Bardram, Jakob

    This paper proposes a service discovery protocol for sensor networks that is specifically tailored for use in humancentered pervasive environments. It uses the high-level concept of computational activities (as logical bundles of data and resources) to give sensors in Activity-Based Sensor Networ....... ABSN enhances the generic Extended Zone Routing Protocol with logical sensor grouping and greatly lowers network overhead during the process of discovery, while keeping discovery latency close to optimal.......This paper proposes a service discovery protocol for sensor networks that is specifically tailored for use in humancentered pervasive environments. It uses the high-level concept of computational activities (as logical bundles of data and resources) to give sensors in Activity-Based Sensor Networks...... (ABSNs) knowledge about their usage even at the network layer. ABSN redesigns classical network-level service discovery protocols to include and use this logical structuring of the network for a more practically applicable service discovery scheme. Noting that in practical settings activity-based sensor...

  7. A systematic approach to novel virus discovery in emerging infectious disease outbreaks.

    Science.gov (United States)

    Sridhar, Siddharth; To, Kelvin K W; Chan, Jasper F W; Lau, Susanna K P; Woo, Patrick C Y; Yuen, Kwok-Yung

    2015-05-01

    The discovery of novel viruses is of great importance to human health-both in the setting of emerging infectious disease outbreaks and in disease syndromes of unknown etiology. Despite the recent proliferation of many efficient virus discovery methods, careful selection of a combination of methods is important to demonstrate a novel virus, its clinical associations, and its relevance in a timely manner. The identification of a patient or an outbreak with distinctive clinical features and negative routine microbiological workup is often the starting point for virus hunting. This review appraises the roles of culture, electron microscopy, and nucleic acid detection-based methods in optimizing virus discovery. Cell culture is generally slow but may yield viable virus. Although the choice of cell line often involves trial and error, it may be guided by the clinical syndrome. Electron microscopy is insensitive but fast, and may provide morphological clues to choice of cell line or consensus primers for nucleic acid detection. Consensus primer PCR can be used to detect viruses that are closely related to known virus families. Random primer amplification and high-throughput sequencing can catch any virus genome but cannot yield an infectious virion for testing Koch postulates. A systematic approach that incorporates carefully chosen combinations of virus detection techniques is required for successful virus discovery. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  8. Fermat's Technique of Finding Areas under Curves

    Science.gov (United States)

    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…

  9. Modular overconstrained weak-link mechanism for ultraprecision motion control

    International Nuclear Information System (INIS)

    Shu Deming; Toellner, Thomas S.; Alp, Esen E.

    2001-01-01

    We have designed and constructed a novel miniature overconstrained weak-link mechanism that will allow positioning of two crystals with better than 50 nrad angular resolution and nanometer linear driving sensitivity. The precision and stability of this structure allow the user to align or adjust an assembly of crystals to achieve the same performance as does a single channel-cut crystal, so we call it an ''artificial channel-cut crystal.'' Unlike the traditional kinematic linear spring mechanisms, the overconstrained weak-link mechanism provides much higher structure stiffness and stability. Using a laminar structure configured and manufactured by chemical etching and lithography techniques, we are able to design and build a planar-shape, high stiffness, high precision weak-link mechanism. In this paper, we present recent developments for the overconstrained weak-link mechanism. Applications of this new technique to synchrotron radiation instrumentation are also discussed

  10. Price discovery in a continuous-time setting

    DEFF Research Database (Denmark)

    Dias, Gustavo Fruet; Fernandes, Marcelo; Scherrer, Cristina

    We formulate a continuous-time price discovery model in which the price discovery measure varies (stochastically) at daily frequency. We estimate daily measures of price discovery using a kernel-based OLS estimator instead of running separate daily VECM regressions as standard in the literature. We...... show that our estimator is not only consistent, but also outperforms the standard daily VECM in finite samples. We illustrate our theoretical findings by studying the price discovery process of 10 actively traded stocks in the U.S. from 2007 to 2013....

  11. Defining Creativity with Discovery

    OpenAIRE

    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 ...

  12. On the antiproton discovery

    International Nuclear Information System (INIS)

    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)

  13. A New parallel Resonant DC-Link Inverter for Soft Switched PWM

    Energy Technology Data Exchange (ETDEWEB)

    Cho, J G; Kim, H S; Cho, G H [Korea Advanced Energy Research Inst., Daeduk-Danji (Korea, Republic of). Korea Nuclear Safety Center

    1993-03-01

    A novel soft switching PWM converter for high frequency AC/DC power conversion is presented by using a new parallel resonant dc-link(PRDCL) and by adopting single phase soft switching(SPSS) technique. The new PRDCL provides variable link pulse position as well as variable link pulse width, which is quite different feature from the other resonant dc-links and thus the PWM capability can be remarkably increased. The SPSS technique is also adopted for further enhancement of PWM capability. Moderate combination of two soft switching operations enables the conventional space vector PWM technique to be used. Due to distinctive advantages including true PWM capability, minimum device voltage stresses(all Vs) and reasonable additional device count(3 devices), the proposed converter can be operated in a wide power range(20-200 KW). Operational principles, analyses and the realization of a space vector PWM of the proposed converter are presented. Simulation results are also shown to verify the operational principle. (author). 15 refs., 14 figs.

  14. 43 CFR 4.826 - Discovery.

    Science.gov (United States)

    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...

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

    DEFF Research Database (Denmark)

    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...

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

    Science.gov (United States)

    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.

  17. Pembelajaran Discovery Learning Untuk Meningkatkan Motivasi Belajar Dan Penguasaan Konsep Siswa

    OpenAIRE

    Anisa, Ewid Nur; Rudibyani, Ratu Betta; Sofya, Emmawaty

    2017-01-01

    The purpose was to describe the practicality, effectiveness and effect size of discovery learning to improve learning motivation and concept mastery on electrolyte and non-electrolyte solution topic. This research was conducted at class X, SMA N 16 Bandar Lampung for 2016/2017 academic year. The poor-experiment research used the one group pretest-posttest design by using technique cluster random sampling, it was obtained sample was the X.8. The data were analyzed descriptively include practic...

  18. "Discoveries in Planetary Sciences": Slide Sets Highlighting New Advances for Astronomy Educators

    Science.gov (United States)

    Brain, D. A.; Schneider, N. M.; Beyer, R. A.

    2010-12-01

    Planetary science is a field that evolves rapidly, motivated by spacecraft mission results. Exciting new mission results are generally communicated rather quickly to the public in the form of press releases and news stories, but it can take several years for new advances to work their way into college textbooks. Yet it is important for students to have exposure to these new advances for a number of reasons. In some cases, new work renders older textbook knowledge incorrect or incomplete. In some cases, new discoveries make it possible to emphasize older textbook knowledge in a new way. In all cases, new advances provide exciting and accessible examples of the scientific process in action. To bridge the gap between textbooks and new advances in planetary sciences we have developed content on new discoveries for use by undergraduate instructors. Called 'Discoveries in Planetary Sciences', each new discovery is summarized in a 3-slide PowerPoint presentation. The first slide describes the discovery, the second slide discusses the underlying planetary science concepts, and the third presents the big picture implications of the discovery. A fourth slide includes links to associated press releases, images, and primary sources. This effort is generously sponsored by the Division for Planetary Sciences of the American Astronomical Society, and the slide sets are available at http://dps.aas.org/education/dpsdisc/. Sixteen slide sets have been released so far covering topics spanning all sub-disciplines of planetary science. Results from the following spacecraft missions have been highlighted: MESSENGER, the Spirit and Opportunity rovers, Cassini, LCROSS, EPOXI, Chandrayan, Mars Reconnaissance Orbiter, Mars Express, and Venus Express. Additionally, new results from Earth-orbiting and ground-based observing platforms and programs such as Hubble, Keck, IRTF, the Catalina Sky Survey, HARPS, MEarth, Spitzer, and amateur astronomers have been highlighted. 4-5 new slide sets are

  19. Native Mass Spectrometry in Fragment-Based Drug Discovery

    Directory of Open Access Journals (Sweden)

    Liliana Pedro

    2016-07-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  1. Physics aids new medical techniques

    CERN Document Server

    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).

  2. Resource-estimation models and predicted discovery

    International Nuclear Information System (INIS)

    Hill, G.W.

    1982-01-01

    Resources have been estimated by predictive extrapolation from past discovery experience, by analogy with better explored regions, or by inference from evidence of depletion of targets for exploration. Changes in technology and new insights into geological mechanisms have occurred sufficiently often in the long run to form part of the pattern of mature discovery experience. The criterion, that a meaningful resource estimate needs an objective measure of its precision or degree of uncertainty, excludes 'estimates' based solely on expert opinion. This is illustrated by development of error measures for several persuasive models of discovery and production of oil and gas in USA, both annually and in terms of increasing exploration effort. Appropriate generalizations of the models resolve many points of controversy. This is illustrated using two USA data sets describing discovery of oil and of U 3 O 8 ; the latter set highlights an inadequacy of available official data. Review of the oil-discovery data set provides a warrant for adjusting the time-series prediction to a higher resource figure for USA petroleum. (author)

  3. Automated discovery systems and the inductivist controversy

    Science.gov (United States)

    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

  4. 7 CFR 283.28 - Discovery.

    Science.gov (United States)

    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...

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

    DEFF Research Database (Denmark)

    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...

  6. Discovery of charm

    International Nuclear Information System (INIS)

    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

  7. Executing SPARQL Queries over the Web of Linked Data

    Science.gov (United States)

    Hartig, Olaf; Bizer, Christian; Freytag, Johann-Christoph

    The Web of Linked Data forms a single, globally distributed dataspace. Due to the openness of this dataspace, it is not possible to know in advance all data sources that might be relevant for query answering. This openness poses a new challenge that is not addressed by traditional research on federated query processing. In this paper we present an approach to execute SPARQL queries over the Web of Linked Data. The main idea of our approach is to discover data that might be relevant for answering a query during the query execution itself. This discovery is driven by following RDF links between data sources based on URIs in the query and in partial results. The URIs are resolved over the HTTP protocol into RDF data which is continuously added to the queried dataset. This paper describes concepts and algorithms to implement our approach using an iterator-based pipeline. We introduce a formalization of the pipelining approach and show that classical iterators may cause blocking due to the latency of HTTP requests. To avoid blocking, we propose an extension of the iterator paradigm. The evaluation of our approach shows its strengths as well as the still existing challenges.

  8. Scientific Discoveries: What Is Required for Lasting Impact.

    Science.gov (United States)

    Lømo, Terje

    2016-01-01

    I have been involved in two scientific discoveries of some impact. One is the discovery of long-term potentiation (LTP), the phenomenon that brief, high-frequency impulse activity at synapses in the brain can lead to long-lasting increases in their efficiency of transmission. This finding demonstrated that synapses are plastic, a property thought to be necessary for learning and memory. The other discovery is that nerve-evoked muscle impulse activity, rather than putative trophic factors, controls the properties of muscle fibers. Here I describe how these two discoveries were made, the unexpected difficulties of reproducing the first discovery, and the controversies that followed the second discovery. I discuss why the first discovery took many years to become generally recognized, whereas the second caused an immediate sensation and entered textbooks and major reviews but is now largely forgotten. In the long run, discovering a new phenomenon has greater impact than falsifying a popular hypothesis.

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

    DEFF Research Database (Denmark)

    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...

  10. 12 CFR 509.102 - Discovery.

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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.

  12. GeoGebra Assist Discovery Learning Model for Problem Solving Ability and Attitude toward Mathematics

    Science.gov (United States)

    Murni, V.; Sariyasa, S.; Ardana, I. M.

    2017-09-01

    This study aims to describe the effet of GeoGebra utilization in the discovery learning model on mathematical problem solving ability and students’ attitude toward mathematics. This research was quasi experimental and post-test only control group design was used in this study. The population in this study was 181 of students. The sampling technique used was cluster random sampling, so the sample in this study was 120 students divided into 4 classes, 2 classes for the experimental class and 2 classes for the control class. Data were analyzed by using one way MANOVA. The results of data analysis showed that the utilization of GeoGebra in discovery learning can lead to solving problems and attitudes towards mathematics are better. This is because the presentation of problems using geogebra can assist students in identifying and solving problems and attracting students’ interest because geogebra provides an immediate response process to students. The results of the research are the utilization of geogebra in the discovery learning can be applied in learning and teaching wider subject matter, beside subject matter in this study.

  13. Maximum Entropy in Drug Discovery

    Directory of Open Access Journals (Sweden)

    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.

  14. Bioinformatics in translational drug discovery.

    Science.gov (United States)

    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. Alternative Polyadenylation Patterns for Novel Gene Discovery and Classification in Cancer

    Directory of Open Access Journals (Sweden)

    Oguzhan Begik

    2017-07-01

    Full Text Available Certain aspects of diagnosis, prognosis, and treatment of cancer patients are still important challenges to be addressed. Therefore, we propose a pipeline to uncover patterns of alternative polyadenylation (APA, a hidden complexity in cancer transcriptomes, to further accelerate efforts to discover novel cancer genes and pathways. Here, we analyzed expression data for 1045 cancer patients and found a significant shift in usage of poly(A signals in common tumor types (breast, colon, lung, prostate, gastric, and ovarian compared to normal tissues. Using machine-learning techniques, we further defined specific subsets of APA events to efficiently classify cancer types. Furthermore, APA patterns were associated with altered protein levels in patients, revealed by antibody-based profiling data, suggesting functional significance. Overall, our study offers a computational approach for use of APA in novel gene discovery and classification in common tumor types, with important implications in basic research, biomarker discovery, and precision medicine approaches.

  16. Search for New Quantum Algorithms

    National Research Council Canada - National Science Library

    Lomonaco, Samuel J; Kauffman, Louis H

    2006-01-01

    .... Additionally, methods and techniques of quantum topology have been used to obtain new results in quantum computing including discovery of a relationship between quantum entanglement and topological linking...

  17. New technique for alpha particles detection

    International Nuclear Information System (INIS)

    Morsy, A.A.; Khattab, F.M.

    1998-01-01

    Man possesses no biological sensors of ionizing radiation as a consequence he must depend entirely on instrumentation for the detection and measurement of radiation. The recent discovery of the solid state nuclear track detection ( SSNTD ) techniques and its advantages over other dosimeters made them a useful tool for radiation dosimetry. This work is devoted to review and illustrate the application of SSNTD technique in some branches of science and technology specially the newly produced TASTRAK obtained from Track Analysis System Limited, Bristol, UK. The detector is successfully irradiated, chemically etched and calibrated for the aim of the Alpha radiation dosimetry

  18. Wallace H. Coulter: decades of invention and discovery.

    Science.gov (United States)

    Robinson, J Paul

    2013-05-01

    Only a few inventors can be said to have made as great an impact on mankind as Wallace Coulter. His inquisitive mind and ability to see well beyond what existed served him well for 40 years of inventing. So many of the fundamental tools that exist today in the area of hematology were derived from or driven by Coulter's inventions that he could be called the most technological innovator in the field of modern hematology. In achieving these discoveries Wallace Coulter was clearly capable of visualizing future opportunities that few others recognized. His vision was combined with an uncanny ability to translate his ideas into products. He developed a large number of tools that shaped the fields of cytometry, image analysis, and industrial materials. His understanding of the future power of computation drove him to link these technologies in a unique way. In the end, Coulter shaped the technologies that ultimately drove hematology in a new direction, one that remains on a critical pathway linking technology innovation all the way to true translational impact. It was said of Henry Ford that "[h]e has no notion that wealth has made him great, and any one who is imprest merely by his wealth bores him. In his personal contacts he likes to dodge the subject. He would prefer to talk with a machinist about machinery, or with somebody who likes birds about birds. In these contacts, he asks no deference; and if he gets it, he suspects it is mere deference to wealth, and that ends his interest."(1) The same could be said of Wallace Coulter, who, like Ford, understood the concepts of mass production and customer service. Coulter had the ability to recognize the opportunity and fulfill the need for development of a blood-cell counter that could be placed in every pathology laboratory, and in so doing transformed a field from a qualitative to a quantitative environment. Every person who has ever entered a medical lab, hospital, or doctor's office has felt the impact of Coulter

  19. Bioanalytical methods for food allergy diagnosis, allergen detection and new allergen discovery

    OpenAIRE

    Gasilova, Natalia; Girault, Hubert H

    2015-01-01

    For effective monitoring and prevention of the food allergy, one of the emerging health problems nowadays, existing diagnostic procedures and allergen detection techniques are constantly improved. Meanwhile, new methods are also developed, and more and more putative allergens are discovered. This review describes traditional methods and summarizes recent advances in the fast evolving field of the in vitro food allergy diagnosis, allergen detection in food products and discovery of the new all...

  20. Arthritis Genetics Analysis Aids Drug Discovery

    Science.gov (United States)

    ... 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 ...

  1. Pharmacokinetic properties and in silico ADME modeling in drug discovery.

    Science.gov (United States)

    Honório, Kathia M; Moda, Tiago L; Andricopulo, Adriano D

    2013-03-01

    The discovery and development of a new drug are time-consuming, difficult and expensive. This complex process has evolved from classical methods into an integration of modern technologies and innovative strategies addressed to the design of new chemical entities to treat a variety of diseases. The development of new drug candidates is often limited by initial compounds lacking reasonable chemical and biological properties for further lead optimization. Huge libraries of compounds are frequently selected for biological screening using a variety of techniques and standard models to assess potency, affinity and selectivity. In this context, it is very important to study the pharmacokinetic profile of the compounds under investigation. Recent advances have been made in the collection of data and the development of models to assess and predict pharmacokinetic properties (ADME--absorption, distribution, metabolism and excretion) of bioactive compounds in the early stages of drug discovery projects. This paper provides a brief perspective on the evolution of in silico ADME tools, addressing challenges, limitations, and opportunities in medicinal chemistry.

  2. A general method for targeted quantitative cross-linking mass spectrometry

    Science.gov (United States)

    Chemical cross-linking mass spectrometry (XL-MS) provides protein structural information by identifying covalently linked proximal amino acid residues on protein surfaces. The information gained by this technique is complementary to other structural biology methods such as x-ray crystallography, NM...

  3. Stochastic network interdiction optimization via capacitated network reliability modeling and probabilistic solution discovery

    International Nuclear Information System (INIS)

    Ramirez-Marquez, Jose Emmanuel; Rocco S, Claudio M.

    2009-01-01

    This paper introduces an evolutionary optimization approach that can be readily applied to solve stochastic network interdiction problems (SNIP). The network interdiction problem solved considers the minimization of the cost associated with an interdiction strategy such that the maximum flow that can be transmitted between a source node and a sink node for a fixed network design is greater than or equal to a given reliability requirement. Furthermore, the model assumes that the nominal capacity of each network link and the cost associated with their interdiction can change from link to link and that such interdiction has a probability of being successful. This version of the SNIP is for the first time modeled as a capacitated network reliability problem allowing for the implementation of computation and solution techniques previously unavailable. The solution process is based on an evolutionary algorithm that implements: (1) Monte-Carlo simulation, to generate potential network interdiction strategies, (2) capacitated network reliability techniques to analyze strategies' source-sink flow reliability and, (3) an evolutionary optimization technique to define, in probabilistic terms, how likely a link is to appear in the final interdiction strategy. Examples for different sizes of networks are used throughout the paper to illustrate the approach

  4. Proteomics for discovery of candidate colorectal cancer biomarkers

    Science.gov (United States)

    Álvarez-Chaver, Paula; Otero-Estévez, Olalla; Páez de la Cadena, María; Rodríguez-Berrocal, Francisco J; Martínez-Zorzano, Vicenta S

    2014-01-01

    Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in Europe and other Western countries, mainly due to the lack of well-validated clinically useful biomarkers with enough sensitivity and specificity to detect this disease at early stages. Although it is well known that the pathogenesis of CRC is a progressive accumulation of mutations in multiple genes, much less is known at the proteome level. Therefore, in the last years many proteomic studies have been conducted to find new candidate protein biomarkers for diagnosis, prognosis and as therapeutic targets for this malignancy, as well as to elucidate the molecular mechanisms of colorectal carcinogenesis. An important advantage of the proteomic approaches is the capacity to look for multiple differentially expressed proteins in a single study. This review provides an overview of the recent reports describing the different proteomic tools used for the discovery of new protein markers for CRC such as two-dimensional electrophoresis methods, quantitative mass spectrometry-based techniques or protein microarrays. Additionally, we will also focus on the diverse biological samples used for CRC biomarker discovery such as tissue, serum and faeces, besides cell lines and murine models, discussing their advantages and disadvantages, and summarize the most frequently identified candidate CRC markers. PMID:24744574

  5. Bioinformatics for cancer immunotherapy target discovery

    DEFF Research Database (Denmark)

    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...

  6. Systems Biology Modeling of the Radiation Sensitivity Network: A Biomarker Discovery Platform

    International Nuclear Information System (INIS)

    Eschrich, Steven; Zhang Hongling; Zhao Haiyan; Boulware, David; Lee, Ji-Hyun; Bloom, Gregory; Torres-Roca, Javier F.

    2009-01-01

    Purpose: The discovery of effective biomarkers is a fundamental goal of molecular medicine. Developing a systems-biology understanding of radiosensitivity can enhance our ability of identifying radiation-specific biomarkers. Methods and Materials: Radiosensitivity, as represented by the survival fraction at 2 Gy was modeled in 48 human cancer cell lines. We applied a linear regression algorithm that integrates gene expression with biological variables, including ras status (mut/wt), tissue of origin and p53 status (mut/wt). Results: The biomarker discovery platform is a network representation of the top 500 genes identified by linear regression analysis. This network was reduced to a 10-hub network that includes c-Jun, HDAC1, RELA (p65 subunit of NFKB), PKC-beta, SUMO-1, c-Abl, STAT1, AR, CDK1, and IRF1. Nine targets associated with radiosensitization drugs are linked to the network, demonstrating clinical relevance. Furthermore, the model identified four significant radiosensitivity clusters of terms and genes. Ras was a dominant variable in the analysis, as was the tissue of origin, and their interaction with gene expression but not p53. Overrepresented biological pathways differed between clusters but included DNA repair, cell cycle, apoptosis, and metabolism. The c-Jun network hub was validated using a knockdown approach in 8 human cell lines representing lung, colon, and breast cancers. Conclusion: We have developed a novel radiation-biomarker discovery platform using a systems biology modeling approach. We believe this platform will play a central role in the integration of biology into clinical radiation oncology practice.

  7. KNODWAT: a scientific framework application for testing knowledge discovery methods for the biomedical domain.

    Science.gov (United States)

    Holzinger, Andreas; Zupan, Mario

    2013-06-13

    Professionals in the biomedical domain are confronted with an increasing mass of data. Developing methods to assist professional end users in the field of Knowledge Discovery to identify, extract, visualize and understand useful information from these huge amounts of data is a huge challenge. However, there are so many diverse methods and methodologies available, that for biomedical researchers who are inexperienced in the use of even relatively popular knowledge discovery methods, it can be very difficult to select the most appropriate method for their particular research problem. A web application, called KNODWAT (KNOwledge Discovery With Advanced Techniques) has been developed, using Java on Spring framework 3.1. and following a user-centered approach. The software runs on Java 1.6 and above and requires a web server such as Apache Tomcat and a database server such as the MySQL Server. For frontend functionality and styling, Twitter Bootstrap was used as well as jQuery for interactive user interface operations. The framework presented is user-centric, highly extensible and flexible. Since it enables methods for testing using existing data to assess suitability and performance, it is especially suitable for inexperienced biomedical researchers, new to the field of knowledge discovery and data mining. For testing purposes two algorithms, CART and C4.5 were implemented using the WEKA data mining framework.

  8. Discovery of the Higgs boson

    CERN Document Server

    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.

  9. Symbol Tables and Branch Tables: Linking Applications Together

    Science.gov (United States)

    Handler, Louis M.

    2011-01-01

    This document explores the computer techniques used to execute software whose parts are compiled and linked separately. The computer techniques include using a branch table or indirect address table to connect the parts. Methods of storing the information in data structures are discussed as well as differences between C and C++.

  10. Ultimate guide to LinkedIn for business

    CERN Document Server

    Prodromou, Ted; Malinchak, James

    2015-01-01

    How To Get Connected with More than 300 Million Customers This popular title delivers an in-depth guide to targeting, reaching, and gaining ideal customers using the latest updates on LinkedIn. LinkedIn expert Ted Prodromou offers a wealth of no- or low-cost methods for maximizing this dynamic resource. Following his lead, readers learn to link with the most effective connections for greater exposure. Updates in this edition include: Staying up-to-date with LinkedIn Contacts, Pulse, and Publisher programs Expansion of premium accounts to help optimize business profiles, stand out in search results, and track impact How to implement new features like Showcase and Company Updates pages for extended presence in newsfeeds and with followers Smarter LinkedIn Search that saves time and money with customized, comprehensive results Other important topics covered include: Techniques and tips to easily navigate LinkedIn's interface Time saving tips on finding and matching data from businesses and people Expert guidance...

  11. Discovery Monday: How to measure success

    CERN Multimedia

    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. Price discovery in European natural gas markets

    International Nuclear Information System (INIS)

    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

  13. Intraday Price Discovery in Fragmented Markets

    NARCIS (Netherlands)

    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

  14. Uranium exploration and evaluation techniques

    International Nuclear Information System (INIS)

    Bowie, S.H.U.

    1977-01-01

    Ground, carborne and airborne surveys for uranium commenced with GM-counters and developed to total-count scintillation counters which have subsequently been replaced to some extent by gamma spectrometers. Stabilisation of the last mentioned is important and has only been achieved recently. Hydrogeochemistry has been revitalised by the introduction of neutron activation analysis and has considerable promise of success in the discovery of surface and near-surface uranium deposits. Soil, stream sediment and lake sediment analyses also have potential particularly in follow-up surveys. One of the most encouraging methods of detecting relatively deeply buried uranium ore bodies is by measuring the radon content of air retained in soil or sub-soil; also that dissolved in stream or lake water. Helium, particularly 4 He, which is also a decay product of uranium but which has an infinite half-life could be measured along with radon. Theoretically this could not only give additional information on buried ore bodies, but on the depth of burial. Another possible technique for use in the detection of buried ore bodies is that of measuring the increased heat flow at surface which, in favourable circumstatnces, should be associated with significant uranium occurrences. Measurement of heat flow could either be by surface thermal sensors or by thermal infra-red scanning techniques from aircraft. For the purposes of preliminary surveys of large areas, airborne geochemical techniques offer considerable scope. Possibilities include the measurement of 222 Rn in the atmosphere. Alternatively, one or more of the decay products of radon could be measured. These are 210 Pb, 210 Bi and 210 Po. It is concluded that there is ample evidence to suggest that the more widespread application of known exploration methods, together with new techniques that can already be envisaged, will result in important new discoveries of uranium reserves

  15. A scientometric prediction of the discovery of the first potentially habitable planet with a mass similar to Earth.

    Directory of Open Access Journals (Sweden)

    Samuel Arbesman

    Full Text Available BACKGROUND: The search for a habitable extrasolar planet has long interested scientists, but only recently have the tools become available to search for such planets. In the past decades, the number of known extrasolar planets has ballooned into the hundreds, and with it, the expectation that the discovery of the first Earth-like extrasolar planet is not far off. METHODOLOGY/PRINCIPAL FINDINGS: Here, we develop a novel metric of habitability for discovered planets and use this to arrive at a prediction for when the first habitable planet will be discovered. Using a bootstrap analysis of currently discovered exoplanets, we predict the discovery of the first Earth-like planet to be announced in the first half of 2011, with the likeliest date being early May 2011. CONCLUSIONS/SIGNIFICANCE: Our predictions, using only the properties of previously discovered exoplanets, accord well with external estimates for the discovery of the first potentially habitable extrasolar planet and highlight the the usefulness of predictive scientometric techniques to understand the pace of scientific discovery in many fields.

  16. Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing

    Directory of Open Access Journals (Sweden)

    Francis A. Ortega

    2018-01-01

    Full Text Available Dynamic clamp, a hybrid-computational-experimental technique that has been used to elucidate ionic mechanisms underlying cardiac electrophysiology, is emerging as a promising tool in the discovery of potential anti-arrhythmic targets and in pharmacological safety testing. Through the injection of computationally simulated conductances into isolated cardiomyocytes in a real-time continuous loop, dynamic clamp has greatly expanded the capabilities of patch clamp outside traditional static voltage and current protocols. Recent applications include fine manipulation of injected artificial conductances to identify promising drug targets in the prevention of arrhythmia and the direct testing of model-based hypotheses. Furthermore, dynamic clamp has been used to enhance existing experimental models by addressing their intrinsic limitations, which increased predictive power in identifying pro-arrhythmic pharmacological compounds. Here, we review the recent advances of the dynamic clamp technique in cardiac electrophysiology with a focus on its future role in the development of safety testing and discovery of anti-arrhythmic drugs.

  17. A Taxonomy of Self-configuring Service Discovery Systems

    NARCIS (Netherlands)

    Sundramoorthy, V.; Hartel, Pieter H.; Scholten, Johan

    2007-01-01

    We analyze the fundamental concepts and issues in service discovery. This analysis places service discovery in the context of distributed systems by describing service discovery as a third generation naming system. We also describe the essential architectures and the functionalities in service

  18. Bioanalytical methods for food allergy diagnosis, allergen detection and new allergen discovery.

    Science.gov (United States)

    Gasilova, Natalia; Girault, Hubert H

    2015-01-01

    For effective monitoring and prevention of the food allergy, one of the emerging health problems nowadays, existing diagnostic procedures and allergen detection techniques are constantly improved. Meanwhile, new methods are also developed, and more and more putative allergens are discovered. This review describes traditional methods and summarizes recent advances in the fast evolving field of the in vitro food allergy diagnosis, allergen detection in food products and discovery of the new allergenic molecules. A special attention is paid to the new diagnostic methods under laboratory development like various immuno- and aptamer-based assays, including immunoaffinity capillary electrophoresis. The latter technique shows the importance of MS application not only for the allergen detection but also for the allergy diagnosis.

  19. Discovery stories in the science classroom

    Science.gov (United States)

    Arya, Diana Jaleh

    School science has been criticized for its lack of emphasis on the tentative, dynamic nature of science as a process of learning more about our world. This criticism is the guiding force for this present body of work, which focuses on the question: what are the educational benefits for middle school students of reading texts that highlight the process of science in the form of a discovery narrative? This dissertation traces my journey through a review of theoretical perspectives of narrative, an analysis of first-hand accounts of scientific discovery, the complex process of developing age-appropriate, cohesive and engaging science texts for middle school students, and a comparison study (N=209) that seeks to determine the unique benefits of the scientific discovery narrative for the interest in and retained understanding of conceptual information presented in middle school science texts. A total of 209 middle school participants in nine different classrooms from two different schools participated in the experimental study. Each subject read two science texts that differed in topic (the qualities of and uses for radioactive elements and the use of telescopic technology to see planets in space) and genre (the discovery narrative and the "conceptually known exposition" comparison text). The differences between the SDN and CKE versions for each topic were equivalent in all possible ways (initial introduction, overall conceptual accuracy, elements of human interest, coherence and readability level), save for the unique components of the discovery narrative (i.e., love for their work, acknowledgement of the known, identification of the unknown and the explorative or experimental process to discovery). Participants generally chose the discovery narrative version as the more interesting of the two texts. Additional findings from the experimental study suggest that science texts in the form of SDNs elicit greater long-term retention of key conceptual information, especially

  20. Empowering pharmacoinformatics by linked life science data.

    Science.gov (United States)

    Goldmann, Daria; Zdrazil, Barbara; Digles, Daniela; Ecker, Gerhard F

    2017-03-01

    With the public availability of large data sources such as ChEMBLdb and the Open PHACTS Discovery Platform, retrieval of data sets for certain protein targets of interest with consistent assay conditions is no longer a time consuming process. Especially the use of workflow engines such as KNIME or Pipeline Pilot allows complex queries and enables to simultaneously search for several targets. Data can then directly be used as input to various ligand- and structure-based studies. In this contribution, using in-house projects on P-gp inhibition, transporter selectivity, and TRPV1 modulation we outline how the incorporation of linked life science data in the daily execution of projects allowed to expand our approaches from conventional Hansch analysis to complex, integrated multilayer models.

  1. Towards a privacy preserving cohort discovery framework for clinical research networks.

    Science.gov (United States)

    Yuan, Jiawei; Malin, Bradley; Modave, François; Guo, Yi; Hogan, William R; Shenkman, Elizabeth; Bian, Jiang

    2017-02-01

    The last few years have witnessed an increasing number of clinical research networks (CRNs) focused on building large collections of data from electronic health records (EHRs), claims, and patient-reported outcomes (PROs). Many of these CRNs provide a service for the discovery of research cohorts with various health conditions, which is especially useful for rare diseases. Supporting patient privacy can enhance the scalability and efficiency of such processes; however, current practice mainly relies on policy, such as guidelines defined in the Health Insurance Portability and Accountability Act (HIPAA), which are insufficient for CRNs (e.g., HIPAA does not require encryption of data - which can mitigate insider threats). By combining policy with privacy enhancing technologies we can enhance the trustworthiness of CRNs. The goal of this research is to determine if searchable encryption can instill privacy in CRNs without sacrificing their usability. We developed a technique, implemented in working software to enable privacy-preserving cohort discovery (PPCD) services in large distributed CRNs based on elliptic curve cryptography (ECC). This technique also incorporates a block indexing strategy to improve the performance (in terms of computational running time) of PPCD. We evaluated the PPCD service with three real cohort definitions: (1) elderly cervical cancer patients who underwent radical hysterectomy, (2) oropharyngeal and tongue cancer patients who underwent robotic transoral surgery, and (3) female breast cancer patients who underwent mastectomy) with varied query complexity. These definitions were tested in an encrypted database of 7.1 million records derived from the publically available Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS). We assessed the performance of the PPCD service in terms of (1) accuracy in cohort discovery, (2) computational running time, and (3) privacy afforded to the underlying records during PPCD. The

  2. Improving data discovery and usability through commentary and user feedback: the CHARMe project

    Science.gov (United States)

    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

  3. Stress transgenerationally programs metabolic pathways linked to altered mental health.

    Science.gov (United States)

    Kiss, Douglas; Ambeskovic, Mirela; Montina, Tony; Metz, Gerlinde A S

    2016-12-01

    Stress is among the primary causes of mental health disorders, which are the most common reason for disability worldwide. The ubiquity of these disorders, and the costs associated with them, lends a sense of urgency to the efforts to improve prediction and prevention. Down-stream metabolic changes are highly feasible and accessible indicators of pathophysiological processes underlying mental health disorders. Here, we show that remote and cumulative ancestral stress programs central metabolic pathways linked to mental health disorders. The studies used a rat model consisting of a multigenerational stress lineage (the great-great-grandmother and each subsequent generation experienced stress during pregnancy) and a transgenerational stress lineage (only the great-great-grandmother was stressed during pregnancy). Urine samples were collected from adult male F4 offspring and analyzed using 1 H NMR spectroscopy. The results of variable importance analysis based on random variable combination were used for unsupervised multivariate principal component analysis and hierarchical clustering analysis, as well as metabolite set enrichment analysis (MSEA) and pathway analysis. We identified distinct metabolic profiles associated with the multigenerational and transgenerational stress phenotype, with consistent upregulation of hippurate and downregulation of tyrosine, threonine, and histamine. MSEA and pathway analysis showed that these metabolites are involved in catecholamine biosynthesis, immune responses, and microbial host interactions. The identification of metabolic signatures linked to ancestral programming assists in the discovery of gene targets for future studies of epigenetic regulation in pathogenic processes. Ultimately, this research can lead to biomarker discovery for better prediction and prevention of mental health disorders.

  4. Predicting future discoveries from current scientific literature.

    Science.gov (United States)

    Petrič, Ingrid; Cestnik, Bojan

    2014-01-01

    Knowledge discovery in biomedicine is a time-consuming process starting from the basic research, through preclinical testing, towards possible clinical applications. Crossing of conceptual boundaries is often needed for groundbreaking biomedical research that generates highly inventive discoveries. We demonstrate the ability of a creative literature mining method to advance valuable new discoveries based on rare ideas from existing literature. When emerging ideas from scientific literature are put together as fragments of knowledge in a systematic way, they may lead to original, sometimes surprising, research findings. If enough scientific evidence is already published for the association of such findings, they can be considered as scientific hypotheses. In this chapter, we describe a method for the computer-aided generation of such hypotheses based on the existing scientific literature. Our literature-based discovery of NF-kappaB with its possible connections to autism was recently approved by scientific community, which confirms the ability of our literature mining methodology to accelerate future discoveries based on rare ideas from existing literature.

  5. Towards linked open gene mutations data

    Science.gov (United States)

    2012-01-01

    Background With the advent of high-throughput technologies, a great wealth of variation data is being produced. Such information may constitute the basis for correlation analyses between genotypes and phenotypes and, in the future, for personalized medicine. Several databases on gene variation exist, but this kind of information is still scarce in the Semantic Web framework. In this paper, we discuss issues related to the integration of mutation data in the Linked Open Data infrastructure, part of the Semantic Web framework. We present the development of a mapping from the IARC TP53 Mutation database to RDF and the implementation of servers publishing this data. Methods A version of the IARC TP53 Mutation database implemented in a relational database was used as first test set. Automatic mappings to RDF were first created by using D2RQ and later manually refined by introducing concepts and properties from domain vocabularies and ontologies, as well as links to Linked Open Data implementations of various systems of biomedical interest. Since D2RQ query performances are lower than those that can be achieved by using an RDF archive, generated data was also loaded into a dedicated system based on tools from the Jena software suite. Results We have implemented a D2RQ Server for TP53 mutation data, providing data on a subset of the IARC database, including gene variations, somatic mutations, and bibliographic references. The server allows to browse the RDF graph by using links both between classes and to external systems. An alternative interface offers improved performances for SPARQL queries. The resulting data can be explored by using any Semantic Web browser or application. Conclusions This has been the first case of a mutation database exposed as Linked Data. A revised version of our prototype, including further concepts and IARC TP53 Mutation database data sets, is under development. The publication of variation information as Linked Data opens new perspectives

  6. Towards linked open gene mutations data.

    Science.gov (United States)

    Zappa, Achille; Splendiani, Andrea; Romano, Paolo

    2012-03-28

    With the advent of high-throughput technologies, a great wealth of variation data is being produced. Such information may constitute the basis for correlation analyses between genotypes and phenotypes and, in the future, for personalized medicine. Several databases on gene variation exist, but this kind of information is still scarce in the Semantic Web framework. In this paper, we discuss issues related to the integration of mutation data in the Linked Open Data infrastructure, part of the Semantic Web framework. We present the development of a mapping from the IARC TP53 Mutation database to RDF and the implementation of servers publishing this data. A version of the IARC TP53 Mutation database implemented in a relational database was used as first test set. Automatic mappings to RDF were first created by using D2RQ and later manually refined by introducing concepts and properties from domain vocabularies and ontologies, as well as links to Linked Open Data implementations of various systems of biomedical interest. Since D2RQ query performances are lower than those that can be achieved by using an RDF archive, generated data was also loaded into a dedicated system based on tools from the Jena software suite. We have implemented a D2RQ Server for TP53 mutation data, providing data on a subset of the IARC database, including gene variations, somatic mutations, and bibliographic references. The server allows to browse the RDF graph by using links both between classes and to external systems. An alternative interface offers improved performances for SPARQL queries. The resulting data can be explored by using any Semantic Web browser or application. This has been the first case of a mutation database exposed as Linked Data. A revised version of our prototype, including further concepts and IARC TP53 Mutation database data sets, is under development.The publication of variation information as Linked Data opens new perspectives: the exploitation of SPARQL searches on

  7. Perspectives of biomolecular NMR in drug discovery: the blessing and curse of versatility

    International Nuclear Information System (INIS)

    Jahnke, Wolfgang

    2007-01-01

    The versatility of NMR and its broad applicability to several stages in the drug discovery process is well known and generally considered one of the major strengths of NMR (Pellecchia et al., Nature Rev Drug Discov 1:211-219, 2002; Stockman and Dalvit, Prog Nucl Magn Reson Spectrosc 41:187-231, 2002; Lepre et al., Comb Chem High throughput screen 5:583-590, 2002; Wyss et al., Curr Opin Drug Discov Devel 5:630-647, 2002; Jahnke and Widmer, Cell Mol Life Sci 61:580-599, 2004; Huth et al., Methods Enzymol 394:549-571, 2005b; Klages et al., Mol Biosyst 2:318-332, 2006; Takeuchi and Wagner, Curr Opin Struct Biol 16:109-117, 2006; Zartler and Shapiro, Curr Pharm Des 12:3963-3972, 2006). Indeed, NMR is the only biophysical technique which can detect and quantify molecular interactions, and at the same time provide detailed structural information with atomic level resolution. NMR should therefore be ideally suited and widely requested as a tool for drug discovery research, and numerous examples of drug discovery projects which have substantially benefited from NMR contributions or were even driven by NMR have been described in the literature. However, not all pharmaceutical companies have rigorously implemented NMR as integral tool of their research processes. Some companies invest with limited resources, and others do not use biomolecular NMR at all. This discrepancy in assessing the value of a technology is striking, and calls for clarification-under which circumstances can NMR provide added value to the drug discovery process? What kind of contributions can NMR make, and how is it implemented and integrated for maximum impact? This perspectives article suggests key areas of impact for NMR, and a model of integrating NMR with other technologies to realize synergies and maximize their value for drug discovery

  8. The neutron discovery

    International Nuclear Information System (INIS)

    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

  9. Viral pathogen discovery

    Science.gov (United States)

    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

  10. User needs analysis and usability assessment of DataMed - a biomedical data discovery index.

    Science.gov (United States)

    Dixit, Ram; Rogith, Deevakar; Narayana, Vidya; Salimi, Mandana; Gururaj, Anupama; Ohno-Machado, Lucila; Xu, Hua; Johnson, Todd R

    2017-11-30

    To present user needs and usability evaluations of DataMed, a Data Discovery Index (DDI) that allows searching for biomedical data from multiple sources. We conducted 2 phases of user studies. Phase 1 was a user needs analysis conducted before the development of DataMed, consisting of interviews with researchers. Phase 2 involved iterative usability evaluations of DataMed prototypes. We analyzed data qualitatively to document researchers' information and user interface needs. Biomedical researchers' information needs in data discovery are complex, multidimensional, and shaped by their context, domain knowledge, and technical experience. User needs analyses validate the need for a DDI, while usability evaluations of DataMed show that even though aggregating metadata into a common search engine and applying traditional information retrieval tools are promising first steps, there remain challenges for DataMed due to incomplete metadata and the complexity of data discovery. Biomedical data poses distinct problems for search when compared to websites or publications. Making data available is not enough to facilitate biomedical data discovery: new retrieval techniques and user interfaces are necessary for dataset exploration. Consistent, complete, and high-quality metadata are vital to enable this process. While available data and researchers' information needs are complex and heterogeneous, a successful DDI must meet those needs and fit into the processes of biomedical researchers. Research directions include formalizing researchers' information needs, standardizing overviews of data to facilitate relevance judgments, implementing user interfaces for concept-based searching, and developing evaluation methods for open-ended discovery systems such as DDIs. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  11. Augmenting collider searches and enhancing discovery potentials through stochastic jet grooming

    Science.gov (United States)

    Roy, Tuhin S.; Thalapillil, Arun M.

    2017-04-01

    The jet trimming procedure has been demonstrated to greatly improve event reconstruction in hadron collisions by mitigating contamination due initial state radiation, multiple interactions, and event pileup. Meanwhile, Qjets—a nondeterministic approach to tree-based jet substructure—has been shown to be a powerful technique in decreasing random statistical fluctuations, yielding significant effective luminosity improvements. This manifests through an improvement in the significance S /δ B , relative to conventional methods. Qjets also provides novel observables in many cases, like mass-volatility, that could be used to further discriminate between signal and background events. The statistical robustness and volatility observables, for tagging, are obtained simultaneously. We explore here a combination of the two techniques, and demonstrate that significant enhancements in discovery potentials may be obtained in nontrivial ways. We will illustrate this by considering a diboson resonance analysis as a case study, enabling us to interpolate between scenarios where the gains are purely due to statistical robustness and scenarios where the gains are also reinforced by volatility variable discriminants. The former, for instance, is applicable to digluon/diquark resonances, while the latter will be of relevance to di -W±/di -Z0 resonances, where the boosted vector bosons are decaying hadronically and have an intrinsic mass scale attached to them. We argue that one can enhance signal significance and discovery potentials markedly through stochastic grooming, and help augment studies at the Large Hadron Collider and future hadron colliders.

  12. Book Review: Dispute Resolution and e-Discovery

    Directory of Open Access Journals (Sweden)

    Milton Luoma

    2012-09-01

    Full Text Available Garrie, D.B., & Griver, Y.M., Eds. (2012. Dispute Resolution and e-Discovery. Thomson Reuters Westlaw, 570 pages, ISBN-13: 9780314604484, US$149.00.Reviewed by Milton Luoma, JD, (Milt.Luoma@metrostate.eduAs is apparent from its title, this book tackles two very current and difficult legal issues – electronic discovery and dispute resolution. The authors tie the two legal concepts together in an effort to provide litigants and practitioners a less expensive and less time consuming alternative than is typically the case with traditional litigation and court proceedings. By including electronic discovery in the discussions, the authors recognize the importance and significance of electronic discovery in mediation and arbitration as it is in traditional litigation.(see PDF for full review

  13. Progress and Potential of Imaging Mass Spectrometry Applied to Biomarker Discovery.

    Science.gov (United States)

    Quanico, Jusal; Franck, Julien; Wisztorski, Maxence; Salzet, Michel; Fournier, Isabelle

    2017-01-01

    Mapping provides a direct means to assess the impact of protein biomarkers and puts into context their relevance in the type of cancer being examined. To this end, mass spectrometry imaging (MSI) was developed to provide the needed spatial information which is missing in traditional liquid-based mass spectrometric proteomics approaches. Aptly described as a "molecular histology" technique, MSI gives an additional dimension in characterizing tumor biopsies, allowing for mapping of hundreds of molecules in a single analysis. A decade of developments focused on improving and standardizing MSI so that the technique can be translated into the clinical setting. This review describes the progress made in addressing the technological development that allows to bridge local protein detection by MSI to its identification and to illustrate its potential in studying various aspects of cancer biomarker discovery.

  14. Computer-Aided Drug Design Applied to Marine Drug Discovery: Meridianins as Alzheimer's Disease Therapeutic Agents.

    Science.gov (United States)

    Llorach-Pares, Laura; Nonell-Canals, Alfons; Sanchez-Martinez, Melchor; Avila, Conxita

    2017-11-27

    Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity found in meridianins A-G, a group of marine indole alkaloids isolated from the marine tunicate Aplidium , against various protein kinases involved in Alzheimer's disease (AD), a neurodegenerative pathology characterized by the presence of neurofibrillary tangles (NFT). Balance splitting between tau kinase and phosphate activities caused tau hyperphosphorylation and, thereby, its aggregation and NTF formation. Inhibition of specific kinases involved in its phosphorylation pathway could be one of the key strategies to reverse tau hyperphosphorylation and would represent an approach to develop drugs to palliate AD symptoms. Meridianins bind to the adenosine triphosphate (ATP) binding site of certain protein kinases, acting as ATP competitive inhibitors. These compounds show very promising scaffolds to design new drugs against AD, which could act over tau protein kinases Glycogen synthetase kinase-3 Beta (GSK3β) and Casein kinase 1 delta (CK1δ, CK1D or KC1D), and dual specificity kinases as dual specificity tyrosine phosphorylation regulated kinase 1 (DYRK1A) and cdc2-like kinases (CLK1). This work is aimed to highlight the role of CADD techniques in marine drug discovery and to provide precise information regarding the binding mode and strength of meridianins against several protein kinases that could help in the future development of anti-AD drugs.

  15. NMR approaches in structure-based lead discovery: recent developments and new frontiers for targeting multi-protein complexes.

    Science.gov (United States)

    Dias, David M; Ciulli, Alessio

    2014-01-01

    Nuclear magnetic resonance (NMR) spectroscopy is a pivotal method for structure-based and fragment-based lead discovery because it is one of the most robust techniques to provide information on protein structure, dynamics and interaction at an atomic level in solution. Nowadays, in most ligand screening cascades, NMR-based methods are applied to identify and structurally validate small molecule binding. These can be high-throughput and are often used synergistically with other biophysical assays. Here, we describe current state-of-the-art in the portfolio of available NMR-based experiments that are used to aid early-stage lead discovery. We then focus on multi-protein complexes as targets and how NMR spectroscopy allows studying of interactions within the high molecular weight assemblies that make up a vast fraction of the yet untargeted proteome. Finally, we give our perspective on how currently available methods could build an improved strategy for drug discovery against such challenging targets. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Imbalanced target prediction with pattern discovery on clinical data repositories.

    Science.gov (United States)

    Chan, Tak-Ming; Li, Yuxi; Chiau, Choo-Chiap; Zhu, Jane; Jiang, Jie; Huo, Yong

    2017-04-20

    Clinical data repositories (CDR) have great potential to improve outcome prediction and risk modeling. However, most clinical studies require careful study design, dedicated data collection efforts, and sophisticated modeling techniques before a hypothesis can be tested. We aim to bridge this gap, so that clinical domain users can perform first-hand prediction on existing repository data without complicated handling, and obtain insightful patterns of imbalanced targets for a formal study before it is conducted. We specifically target for interpretability for domain users where the model can be conveniently explained and applied in clinical practice. We propose an interpretable pattern model which is noise (missing) tolerant for practice data. To address the challenge of imbalanced targets of interest in clinical research, e.g., deaths less than a few percent, the geometric mean of sensitivity and specificity (G-mean) optimization criterion is employed, with which a simple but effective heuristic algorithm is developed. We compared pattern discovery to clinically interpretable methods on two retrospective clinical datasets. They contain 14.9% deaths in 1 year in the thoracic dataset and 9.1% deaths in the cardiac dataset, respectively. In spite of the imbalance challenge shown on other methods, pattern discovery consistently shows competitive cross-validated prediction performance. Compared to logistic regression, Naïve Bayes, and decision tree, pattern discovery achieves statistically significant (p-values repositories with imbalance and noise. The prediction results and interpretable patterns can provide insights in an agile and inexpensive way for the potential formal studies.

  17. The mass-action law based algorithm for cost-effective approach for cancer drug discovery and development.

    Science.gov (United States)

    Chou, Ting-Chao

    2011-01-01

    The mass-action law based system analysis via mathematical induction and deduction lead to the generalized theory and algorithm that allows computerized simulation of dose-effect dynamics with small size experiments using a small number of data points in vitro, in animals, and in humans. The median-effect equation of the mass-action law deduced from over 300 mechanism specific-equations has been shown to be the unified theory that serves as the common-link for complicated biomedical systems. After using the median-effect principle as the common denominator, its applications are mechanism-independent, drug unit-independent, and dynamic order-independent; and can be used generally for single drug analysis or for multiple drug combinations in constant-ratio or non-constant ratios. Since the "median" is the common link and universal reference point in biological systems, these general enabling lead to computerized quantitative bio-informatics for econo-green bio-research in broad disciplines. Specific applications of the theory, especially relevant to drug discovery, drug combination, and clinical trials, have been cited or illustrated in terms of algorithms, experimental design and computerized simulation for data analysis. Lessons learned from cancer research during the past fifty years provide a valuable opportunity to reflect, and to improve the conventional divergent approach and to introduce a new convergent avenue, based on the mass-action law principle, for the efficient cancer drug discovery and the low-cost drug development.

  18. Asymmetric threat data mining and knowledge discovery

    Science.gov (United States)

    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.

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

    NARCIS (Netherlands)

    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

  20. A General Method for Targeted Quantitative Cross-Linking Mass Spectrometry.

    Directory of Open Access Journals (Sweden)

    Juan D Chavez

    Full Text Available Chemical cross-linking mass spectrometry (XL-MS provides protein structural information by identifying covalently linked proximal amino acid residues on protein surfaces. The information gained by this technique is complementary to other structural biology methods such as x-ray crystallography, NMR and cryo-electron microscopy[1]. The extension of traditional quantitative proteomics methods with chemical cross-linking can provide information on the structural dynamics of protein structures and protein complexes. The identification and quantitation of cross-linked peptides remains challenging for the general community, requiring specialized expertise ultimately limiting more widespread adoption of the technique. We describe a general method for targeted quantitative mass spectrometric analysis of cross-linked peptide pairs. We report the adaptation of the widely used, open source software package Skyline, for the analysis of quantitative XL-MS data as a means for data analysis and sharing of methods. We demonstrate the utility and robustness of the method with a cross-laboratory study and present data that is supported by and validates previously published data on quantified cross-linked peptide pairs. This advance provides an easy to use resource so that any lab with access to a LC-MS system capable of performing targeted quantitative analysis can quickly and accurately measure dynamic changes in protein structure and protein interactions.

  1. 40 CFR 209.22 - Other discovery.

    Science.gov (United States)

    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...

  2. Effective Online Group Discovery in Trajectory Databases

    DEFF Research Database (Denmark)

    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...

  3. Urban rainfall estimation employing commercial microwave links

    Science.gov (United States)

    Overeem, Aart; Leijnse, Hidde; Uijlenhoet, Remko; ten Veldhuis, Marie-claire

    2015-04-01

    Urban areas often lack rainfall information. To increase the number of rainfall observations in cities, microwave links from operational cellular telecommunication networks may be employed. Although this new potential source of rainfall information has been shown to be promising, its quality needs to be demonstrated more extensively. In the Rain Sense kickstart project of the Amsterdam Institute for Advanced Metropolitan Solutions (AMS), sensors and citizens are preparing Amsterdam for future weather. Part of this project is rainfall estimation using new measurement techniques. Innovative sensing techniques will be utilized such as rainfall estimation from microwave links, umbrellas for weather sensing, low-cost sensors at lamp posts and in drainage pipes for water level observation. These will be combined with information provided by citizens in an active way through smartphone apps and in a passive way through social media posts (Twitter, Flickr etc.). Sensor information will be integrated, visualized and made accessible to citizens to help raise citizen awareness of urban water management challenges and promote resilience by providing information on how citizens can contribute in addressing these. Moreover, citizens and businesses can benefit from reliable weather information in planning their social and commercial activities. In the end city-wide high-resolution rainfall maps will be derived, blending rainfall information from microwave links and weather radars. This information will be used for urban water management. This presentation focuses on rainfall estimation from commercial microwave links. Received signal levels from tens of microwave links within the Amsterdam region (roughly 1 million inhabitants) in the Netherlands are utilized to estimate rainfall with high spatial and temporal resolution. Rainfall maps will be presented and compared to a gauge-adjusted radar rainfall data set. Rainfall time series from gauge(s), radars and links will be compared.

  4. Arrayed antibody library technology for therapeutic biologic discovery.

    Science.gov (United States)

    Bentley, Cornelia A; Bazirgan, Omar A; Graziano, James J; Holmes, Evan M; Smider, Vaughn V

    2013-03-15

    Traditional immunization and display antibody discovery methods rely on competitive selection amongst a pool of antibodies to identify a lead. While this approach has led to many successful therapeutic antibodies, targets have been limited to proteins which are easily purified. In addition, selection driven discovery has produced a narrow range of antibody functionalities focused on high affinity antagonism. We review the current progress in developing arrayed protein libraries for screening-based, rather than selection-based, discovery. These single molecule per microtiter well libraries have been screened in multiplex formats against both purified antigens and directly against targets expressed on the cell surface. This facilitates the discovery of antibodies against therapeutically interesting targets (GPCRs, ion channels, and other multispanning membrane proteins) and epitopes that have been considered poorly accessible to conventional discovery methods. Copyright © 2013. Published by Elsevier Inc.

  5. A virtual high-throughput screening approach to the discovery of novel inhibitors of the bacterial leucine transporter, LeuT

    DEFF Research Database (Denmark)

    Simmons, Katie J; Gotfryd, Kamil; Billesbølle, Christian B

    2013-01-01

    Abstract Membrane proteins are intrinsically involved in both human and pathogen physiology, and are the target of 60% of all marketed drugs. During the past decade, advances in the studies of membrane proteins using X-ray crystallography, electron microscopy and NMR-based techniques led to the e...... this is a virtual high-throughput screening (vHTS) technique initially developed for soluble proteins. This paper describes application of this technique to the discovery of inhibitors of the leucine transporter (LeuT), a member of the neurotransmitter:sodium symporter (NSS) family....

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

    DEFF Research Database (Denmark)

    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...

  7. Measuring urban rainfall using microwave links from commercial cellular communication networks

    NARCIS (Netherlands)

    Overeem, A.; Leijnse, H.; Uijlenhoet, R.

    2011-01-01

    The estimation of rainfall using commercial microwave links is a new and promising measurement technique. Commercial link networks cover large parts of the land surface of the earth and have a high density, particularly in urban areas. Rainfall attenuates the electromagnetic signals transmitted

  8. Radioactivity. Centenary of radioactivity discovery

    International Nuclear Information System (INIS)

    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.)

  9. Near-Earth Object Orbit Linking with the Large Synoptic Survey Telescope

    Science.gov (United States)

    Vereš, Peter; Chesley, Steven R.

    2017-07-01

    We have conducted a detailed simulation of the ability of the Large Synoptic Survey Telescope (LSST) to link near-Earth and main belt asteroid detections into orbits. The key elements of the study were a high-fidelity detection model and the presence of false detections in the form of both statistical noise and difference image artifacts. We employed the Moving Object Processing System (MOPS) to generate tracklets, tracks, and orbits with a realistic detection density for one month of the LSST survey. The main goals of the study were to understand whether (a) the linking of near-Earth objects (NEOs) into orbits can succeed in a realistic survey, (b) the number of false tracks and orbits will be manageable, and (c) the accuracy of linked orbits would be sufficient for automated processing of discoveries and attributions. We found that the overall density of asteroids was more than 5000 per LSST field near opposition on the ecliptic, plus up to 3000 false detections per field in good seeing. We achieved 93.6% NEO linking efficiency for H< 22 on tracks composed of tracklets from at least three distinct nights within a 12 day interval. The derived NEO catalog was comprised of 96% correct linkages. Less than 0.1% of orbits included false detections, and the remainder of false linkages stemmed from main belt confusion, which was an artifact of the short time span of the simulation. The MOPS linking efficiency can be improved by refined attribution of detections to known objects and by improved tuning of the internal kd-tree linking algorithms.

  10. Discovery Mondays - Gases: more to them than meets the eye!

    CERN Multimedia

    2005-01-01

    We generally tend to think that if a space is empty there is nothing in it. However, did you know that at the Earth's surface there are 25 million million million (1018) molecules of gas in every cubic centimetre of atmosphere? CERN uses a lot of gas to operate its experiments. Above a few of the helium tanks for the LHC. At CERN, gases are put to multiple uses. Gases are used to protect, to cool and also to detect particles... Suffice to say that gases play a vital role at CERN. Why does the air supply to the accelerator tunnel 100 metres below the surface have to be treated and what treatment techniques are used? What are the different types of apparatus that enable you to breathe in confined spaces? How are gases used as a detection medium in the particle detectors? What is Brownian motion? To find out the answers, step on the gas to join us for the next Discovery Monday! This Discovery Monday will be taking place as part of the World Year of Physics, as its theme is closely associated with one of the ...

  11. Discovery Mondays - Gases: more to them than meets the eye!

    CERN Multimedia

    2005-01-01

    CERN uses a lot of gas to operate its experiments. Above a few of the helium tanks for the LHC. We generally tend to think that if a space is empty there is nothing in it. However, did you know that at the Earth's surface there are 25 million million million (1018) molecules of gas in every cubic centimetre of atmosphere? At CERN, gases are put to multiple uses. They are used to protect, to cool and also to detect particles... Suffice it to say that gases play a vital role at CERN. Why does the air supply to the accelerator tunnel 100 metres below the surface have to be treated and what treatment techniques are used? What are the different types of apparatus that enable you to breathe in confined spaces? How are gases used as a detection medium in the particle detectors? How are vacuums made? To find out the answers, step on the gas and join us for the next Discovery Monday! This Discovery Monday will be taking place as part of the World Year of Physics, as its theme is closely associated with one of the ...

  12. Teaching Techniques: Audiovisual Feedback in EFL/ESL Writing Classes

    Science.gov (United States)

    Woodard, William J.

    2016-01-01

    In this article, William J. Woodard, an English teacher preparing students for university-level work in academic English, describes a more effective student feedback technique that decreases the amount of time spent writing such feedback. Woodard explains his discovery of the tool "Jing." Jing is a free application for PCs and Macs by…

  13. Enzymatic cellulose oxidation is linked to lignin by long-range electron transfer

    DEFF Research Database (Denmark)

    Westereng, Bjorge; Cannella, David; Wittrup Agger, Jane

    2015-01-01

    in biological systems are only partly understood. We show here that insoluble high molecular weight lignin functions as a reservoir of electrons facilitating LPMO activity. The electrons are donated to the enzyme by long-range electron transfer involving soluble low molecular weight lignins present in plant...... cell walls. Electron transfer was confirmed by electron paramagnetic resonance spectroscopy showing that LPMO activity on cellulose changes the level of unpaired electrons in the lignin. The discovery of a long-range electron transfer mechanism links the biodegradation of cellulose and lignin and sheds...

  14. On the threshold of discovery

    International Nuclear Information System (INIS)

    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.)

  15. The discovery of human auditory-motor entrainment and its role in the development of neurologic music therapy.

    Science.gov (United States)

    Thaut, Michael H

    2015-01-01

    The discovery of rhythmic auditory-motor entrainment in clinical populations was a historical breakthrough in demonstrating for the first time a neurological mechanism linking music to retraining brain and behavioral functions. Early pilot studies from this research center were followed up by a systematic line of research studying rhythmic auditory stimulation on motor therapies for stroke, Parkinson's disease, traumatic brain injury, cerebral palsy, and other movement disorders. The comprehensive effects on improving multiple aspects of motor control established the first neuroscience-based clinical method in music, which became the bedrock for the later development of neurologic music therapy. The discovery of entrainment fundamentally shifted and extended the view of the therapeutic properties of music from a psychosocially dominated view to a view using the structural elements of music to retrain motor control, speech and language function, and cognitive functions such as attention and memory. © 2015 Elsevier B.V. All rights reserved.

  16. Thermometric enzyme linked immunosorbent assay: TELISA.

    Science.gov (United States)

    Mattiasson, B; Borrebaeck, C; Sanfridson, B; Mosbach, K

    1977-08-11

    A new method, thermometric enzyme linked immunosorbent assay (TELISA), for the assay of endogenous and exogenous compounds in biological fluids is described. It is based on the previously described enzyme linked immunosorbent assay technique, ELISA, but utilizes enzymic heat formation which is measured in an enzyme thermistor unit. In the model system studied determination of human serum albumin down to a concentration of 10(-10) M (5 ng/ml) was achieved, with both normal and catalase labelled human serum albumin competing for the binding sites on the immunosorbent, which was rabbit antihuman serum albumin immobilized onto Sepharose CL-4B.

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

    Science.gov (United States)

    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

  18. Emerging Concepts and Methodologies in Cancer Biomarker Discovery.

    Science.gov (United States)

    Lu, Meixia; Zhang, Jinxiang; Zhang, Lanjing

    2017-01-01

    Cancer biomarker discovery is a critical part of cancer prevention and treatment. Despite the decades of effort, only a small number of cancer biomarkers have been identified for and validated in clinical settings. Conceptual and methodological breakthroughs may help accelerate the discovery of additional cancer biomarkers, particularly their use for diagnostics. In this review, we have attempted to review the emerging concepts in cancer biomarker discovery, including real-world evidence, open access data, and data paucity in rare or uncommon cancers. We have also summarized the recent methodological progress in cancer biomarker discovery, such as high-throughput sequencing, liquid biopsy, big data, artificial intelligence (AI), and deep learning and neural networks. Much attention has been given to the methodological details and comparison of the methodologies. Notably, these concepts and methodologies interact with each other and will likely lead to synergistic effects when carefully combined. Newer, more innovative concepts and methodologies are emerging as the current emerging ones became mainstream and widely applied to the field. Some future challenges are also discussed. This review contributes to the development of future theoretical frameworks and technologies in cancer biomarker discovery and will contribute to the discovery of more useful cancer biomarkers.

  19. 120 YEARS SINCE THE DISCOVERY OF X-RAYS.

    Science.gov (United States)

    Babic, Rade R; Stankovic Babic, Gordana; Babic, Strahinja R; Babic, Nevena R

    2016-09-01

    This paper is intended to celebrate the 120th anniversary of the discovery of X-rays. X-rays (Roentgen-rays) were discovered on the 8th ofNovember, 1895 by the German physicist Wilhelm Conrad Roentgen. Fifty days after the discovery of X-ray, on December 28, 1895. Wilhelm Conrad Roentgen published a paper about the discovery of X-rays - "On a new kind of rays" (Wilhelm Conrad Roentgen: Ober eine neue Art von Strahlen. In: Sitzungsberichte der Wurzburger Physik.-Medic.- Gesellschaft. 1895.). Therefore, the date of 28th ofDecember, 1895 was taken as the date of X-rays discovery. This paper describes the work of Wilhelm Conrad Roentgen, Nikola Tesla, Mihajlo Pupin and Maria Sklodowska-Curie about the nature of X-rays . The fantastic four - Wilhelm Conrad Roentgen, NikolaTesla, Mihajlo ldvorski Pupin and Maria Sklodowska-Curie set the foundation of radiology with their discovery and study of X-rays. Five years after the discovery of X-rays, in 1900, Dr Avram Vinaver had the first X-ray machine installed in abac, in Serbia at the time when many developed countries did not have an X-ray machine and thus set the foundation of radiology in Serbia.

  20. On reliable discovery of molecular signatures

    Directory of Open Access Journals (Sweden)

    Björkegren Johan

    2009-01-01

    Full Text Available Abstract Background Molecular signatures are sets of genes, proteins, genetic variants or other variables that can be used as markers for a particular phenotype. Reliable signature discovery methods could yield valuable insight into cell biology and mechanisms of human disease. However, it is currently not clear how to control error rates such as the false discovery rate (FDR in signature discovery. Moreover, signatures for cancer gene expression have been shown to be unstable, that is, difficult to replicate in independent studies, casting doubts on their reliability. Results We demonstrate that with modern prediction methods, signatures that yield accurate predictions may still have a high FDR. Further, we show that even signatures with low FDR may fail to replicate in independent studies due to limited statistical power. Thus, neither stability nor predictive accuracy are relevant when FDR control is the primary goal. We therefore develop a general statistical hypothesis testing framework that for the first time provides FDR control for signature discovery. Our method is demonstrated to be correct in simulation studies. When applied to five cancer data sets, the method was able to discover molecular signatures with 5% FDR in three cases, while two data sets yielded no significant findings. Conclusion Our approach enables reliable discovery of molecular signatures from genome-wide data with current sample sizes. The statistical framework developed herein is potentially applicable to a wide range of prediction problems in bioinformatics.

  1. Resource Discovery in Activity-Based Sensor Networks

    DEFF Research Database (Denmark)

    Bucur, Doina; Bardram, Jakob

    This paper proposes a service discovery protocol for sensor networks that is specifically tailored for use in humancentered pervasive environments. It uses the high-level concept of computational activities (as logical bundles of data and resources) to give sensors in Activity-Based Sensor Networks...... (ABSNs) knowledge about their usage even at the network layer. ABSN redesigns classical network-level service discovery protocols to include and use this logical structuring of the network for a more practically applicable service discovery scheme. Noting that in practical settings activity-based sensor...

  2. Discovery and Innovation

    African Journals Online (AJOL)

    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. A Ligand-observed Mass Spectrometry Approach Integrated into the Fragment Based Lead Discovery Pipeline

    Science.gov (United States)

    Chen, Xin; Qin, Shanshan; Chen, Shuai; Li, Jinlong; Li, Lixin; Wang, Zhongling; Wang, Quan; Lin, Jianping; Yang, Cheng; Shui, Wenqing

    2015-01-01

    In fragment-based lead discovery (FBLD), a cascade combining multiple orthogonal technologies is required for reliable detection and characterization of fragment binding to the target. Given the limitations of the mainstream screening techniques, we presented a ligand-observed mass spectrometry approach to expand the toolkits and increase the flexibility of building a FBLD pipeline especially for tough targets. In this study, this approach was integrated into a FBLD program targeting the HCV RNA polymerase NS5B. Our ligand-observed mass spectrometry analysis resulted in the discovery of 10 hits from a 384-member fragment library through two independent screens of complex cocktails and a follow-up validation assay. Moreover, this MS-based approach enabled quantitative measurement of weak binding affinities of fragments which was in general consistent with SPR analysis. Five out of the ten hits were then successfully translated to X-ray structures of fragment-bound complexes to lay a foundation for structure-based inhibitor design. With distinctive strengths in terms of high capacity and speed, minimal method development, easy sample preparation, low material consumption and quantitative capability, this MS-based assay is anticipated to be a valuable addition to the repertoire of current fragment screening techniques. PMID:25666181

  4. Discovery Mondays: Zoom on materials

    CERN Multimedia

    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...

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

    National Research Council Canada - National Science Library

    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 ...

  6. DEVELOPING GUIDED DISCOVERY LEARNING MATERIALS USING MATHEMATICS MOBILE LEARNING APPLICATION AS AN ALTERNATIVE MEDIA FOR THE STUDENTS CALCULUS II

    Directory of Open Access Journals (Sweden)

    Sunismi .

    2015-12-01

    Full Text Available Abstract: The development research aims to develop guided-discovery learning materials of Calculus II by implementing Mathematics Mobile Learning (MML. The products to develop are MML media of Calculus II using guided discovery model for students and a guide book for lecturers. The study employed used 4-D development model consisting of define, design, develop, and disseminate. The draft of the learning materials was validated by experts and tried-out to a group of students. The data were analyzed qualitatively and quantitatively by using a descriptive technique and t-test. The findings of the research were appropriate to be used ad teaching media for the students. The students responded positively that the MML media of Calculus II using the guided-discovery model was interestingly structured, easily operated through handphones (all JAVA, android, and blackberry-based handphones to be used as their learning guide anytime. The result of the field testing showed that the guided-discovery learning materials of Calculus II using the Mathematics Mobile Learning (MML application was effective to adopt in learning Calculus II. Keywords: learning materials, guided-discovery, mathematics mobile learning (MML, calculus II PENGEMBANGAN BAHAN AJAR MODEL GUIDED DISCOVERY DENGAN APLIKASI MATHEMATICS MOBILE LEARNING SEBAGAI ALTERNATIF MEDIA PEMBELAJARAN MAHASISWA MATAKULIAH KALKULUS II Abstrak: Penelitian pengembangan ini bertujuan untuk mengembangkan bahan ajar matakuliah Kalkulus II model guided discovery dengan aplikasi Mathematics Mobile Learning (MML. Produk yang dikembangkan berupa media MML Kalkulus II dengan model guided discovery untuk mahasiswa dan buku panduan dosen. Model pengembangan menggunakan 4-D yang meliputi tahap define, design, develop, dan dissemination. Draf bahan ajar divalidasi oleh pakar dan diujicobakan kepada sejumlah mahasiswa. Data dianalisis secara kualitatif dan kuantitatif dengan teknik deskriptif dan uji t. Temuan penelitian

  7. Single-step emulation of nonlinear fiber-optic link with gaussian mixture model

    DEFF Research Database (Denmark)

    Borkowski, Robert; Doberstein, Andy; Haisch, Hansjörg

    2015-01-01

    We use a fast and low-complexity statistical signal processing method to emulate nonlinear noise in fiber links. The proposed emulation technique stands in good agreement with the numerical NLSE simulation for 32 Gbaud DP-16QAM nonlinear transmission.......We use a fast and low-complexity statistical signal processing method to emulate nonlinear noise in fiber links. The proposed emulation technique stands in good agreement with the numerical NLSE simulation for 32 Gbaud DP-16QAM nonlinear transmission....

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

    CERN Document Server

    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...

  9. The Higgs Boson Search and Discovery

    CERN Document Server

    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...

  10. History of the discovery of uranium fission by neutrons

    International Nuclear Information System (INIS)

    Simane, C.

    1989-01-01

    The history is briefly described of the discovery of uranium fission by neutrons, based on the texts of original scientific studies, memories or biographies of those who participated in the discovery and of their contemporaries. Obstacles that stood in the way of the discovery are discussed. It is stated that only a few scientists contributed to the discovery of uranium fission. The fission process itself still remains subject of physical research which studies its detailed laws. (Z.M.). 2 tabs., 16 refs

  11. Discovery of the calcium, indium, tin, and platinum isotopes

    International Nuclear Information System (INIS)

    Amos, S.; Gross, J.L.; Thoennessen, M.

    2011-01-01

    Currently, twenty-four calcium, thirty-eight indium, thirty-eight tin, and thirty-nine platinum isotopes have been observed and the discovery of these isotopes is discussed here. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented. - Highlights: Documentation of the discovery of all calcium, indium, tin and platinum isotopes. → Summary of author, journal, year, place and country of discovery for each isotope. → Brief description of discovery history of each isotope.

  12. Orphan diseases: state of the drug discovery art.

    Science.gov (United States)

    Volmar, Claude-Henry; Wahlestedt, Claes; Brothers, Shaun P

    2017-06-01

    Since 1983 more than 300 drugs have been developed and approved for orphan diseases. However, considering the development of novel diagnosis tools, the number of rare diseases vastly outpaces therapeutic discovery. Academic centers and nonprofit institutes are now at the forefront of rare disease R&D, partnering with pharmaceutical companies when academic researchers discover novel drugs or targets for specific diseases, thus reducing the failure risk and cost for pharmaceutical companies. Considerable progress has occurred in the art of orphan drug discovery, and a symbiotic relationship now exists between pharmaceutical industry, academia, and philanthropists that provides a useful framework for orphan disease therapeutic discovery. Here, the current state-of-the-art of drug discovery for orphan diseases is reviewed. Current technological approaches and challenges for drug discovery are considered, some of which can present somewhat unique challenges and opportunities in orphan diseases, including the potential for personalized medicine, gene therapy, and phenotypic screening.

  13. Discovery learning with SAVI approach in geometry learning

    Science.gov (United States)

    Sahara, R.; Mardiyana; Saputro, D. R. S.

    2018-05-01

    Geometry is one branch of mathematics that an important role in learning mathematics in the schools. This research aims to find out about Discovery Learning with SAVI approach to achievement of learning geometry. This research was conducted at Junior High School in Surakarta city. Research data were obtained through test and questionnaire. Furthermore, the data was analyzed by using two-way Anova. The results showed that Discovery Learning with SAVI approach gives a positive influence on mathematics learning achievement. Discovery Learning with SAVI approach provides better mathematics learning outcomes than direct learning. In addition, students with high self-efficacy categories have better mathematics learning achievement than those with moderate and low self-efficacy categories, while student with moderate self-efficacy categories are better mathematics learning achievers than students with low self-efficacy categories. There is an interaction between Discovery Learning with SAVI approach and self-efficacy toward student's mathematics learning achievement. Therefore, Discovery Learning with SAVI approach can improve mathematics learning achievement.

  14. The Dynamic Radio Sky: An Opportunity for Discovery

    Science.gov (United States)

    2010-01-01

    giant pulses from the Crab pulsar , a small number of dedicated radio transient surveys, and the serendipitous discovery of transient radio sources...used in the discovery of over 1800 radio pulsars . In 2003, the Parkes Multibeam Survey had covered the entire Galactic plane visible from Parkes... pulsars , and confirmed the neutron star nature of these sources, dubbed Rotating Radio Transients (RRATs). Since the discovery of the original 11 RRATs

  15. Solid Phase Microextraction and Related Techniques for Drugs in Biological Samples

    OpenAIRE

    Moein, Mohammad Mahdi; Said, Rana; Bassyouni, Fatma; Abdel-Rehim, Mohamed

    2014-01-01

    In drug discovery and development, the quantification of drugs in biological samples is an important task for the determination of the physiological performance of the investigated drugs. After sampling, the next step in the analytical process is sample preparation. Because of the low concentration levels of drug in plasma and the variety of the metabolites, the selected extraction technique should be virtually exhaustive. Recent developments of sample handling techniques are directed, from o...

  16. Discovery as a process

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Daily life activity routine discovery in hemiparetic rehabilitation patients using topic models.

    Science.gov (United States)

    Seiter, J; Derungs, A; Schuster-Amft, C; Amft, O; Tröster, G

    2015-01-01

    Monitoring natural behavior and activity routines of hemiparetic rehabilitation patients across the day can provide valuable progress information for therapists and patients and contribute to an optimized rehabilitation process. In particular, continuous patient monitoring could add type, frequency and duration of daily life activity routines and hence complement standard clinical scores that are assessed for particular tasks only. Machine learning methods have been applied to infer activity routines from sensor data. However, supervised methods require activity annotations to build recognition models and thus require extensive patient supervision. Discovery methods, including topic models could provide patient routine information and deal with variability in activity and movement performance across patients. Topic models have been used to discover characteristic activity routine patterns of healthy individuals using activity primitives recognized from supervised sensor data. Yet, the applicability of topic models for hemiparetic rehabilitation patients and techniques to derive activity primitives without supervision needs to be addressed. We investigate, 1) whether a topic model-based activity routine discovery framework can infer activity routines of rehabilitation patients from wearable motion sensor data. 2) We compare the performance of our topic model-based activity routine discovery using rule-based and clustering-based activity vocabulary. We analyze the activity routine discovery in a dataset recorded with 11 hemiparetic rehabilitation patients during up to ten full recording days per individual in an ambulatory daycare rehabilitation center using wearable motion sensors attached to both wrists and the non-affected thigh. We introduce and compare rule-based and clustering-based activity vocabulary to process statistical and frequency acceleration features to activity words. Activity words were used for activity routine pattern discovery using topic models

  18. Discovery of a Novel Inhibitor of the Hedgehog Signaling Pathway through Cell-based Compound Discovery and Target Prediction.

    Science.gov (United States)

    Kremer, Lea; Schultz-Fademrecht, Carsten; Baumann, Matthias; Habenberger, Peter; Choidas, Axel; Klebl, Bert; Kordes, Susanne; Schöler, Hans R; Sterneckert, Jared; Ziegler, Slava; Schneider, Gisbert; Waldmann, Herbert

    2017-10-09

    Cell-based assays enable monitoring of small-molecule bioactivity in a target-agnostic manner and help uncover new biological mechanisms. Subsequent identification and validation of the small-molecule targets, typically employing proteomics techniques, is very challenging and limited, in particular if the targets are membrane proteins. Herein, we demonstrate that the combination of cell-based bioactive-compound discovery with cheminformatic target prediction may provide an efficient approach to accelerate the process and render target identification and validation more efficient. Using a cell-based assay, we identified the pyrazolo-imidazole smoothib as a new inhibitor of hedgehog (Hh) signaling and an antagonist of the protein smoothened (SMO) with a novel chemotype. Smoothib targets the heptahelical bundle of SMO, prevents its ciliary localization, reduces the expression of Hh target genes, and suppresses the growth of Ptch +/- medulloblastoma cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Fragment-Linking Approach Using (19)F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of β-Secretase.

    Science.gov (United States)

    Jordan, John B; Whittington, Douglas A; Bartberger, Michael D; Sickmier, E Allen; Chen, Kui; Cheng, Yuan; Judd, Ted

    2016-04-28

    Fragment-based drug discovery (FBDD) has become a widely used tool in small-molecule drug discovery efforts. One of the most commonly used biophysical methods in detecting weak binding of fragments is nuclear magnetic resonance (NMR) spectroscopy. In particular, FBDD performed with (19)F NMR-based methods has been shown to provide several advantages over (1)H NMR using traditional magnetization-transfer and/or two-dimensional methods. Here, we demonstrate the utility and power of (19)F-based fragment screening by detailing the identification of a second-site fragment through (19)F NMR screening that binds to a specific pocket of the aspartic acid protease, β-secretase (BACE-1). The identification of this second-site fragment allowed the undertaking of a fragment-linking approach, which ultimately yielded a molecule exhibiting a more than 360-fold increase in potency while maintaining reasonable ligand efficiency and gaining much improved selectivity over cathepsin-D (CatD). X-ray crystallographic studies of the molecules demonstrated that the linked fragments exhibited binding modes consistent with those predicted from the targeted screening approach, through-space NMR data, and molecular modeling.

  20. Planetary Science Research Discoveries (PSRD) www.psrd.hawaii.edu

    Science.gov (United States)

    Martel, L.; Taylor, J.

    2010-12-01

    NASA's Year of the Solar System is celebrating not only Solar System mission milestones but also the collective data reduction and analysis that happens here on Earth. The Cosmochemistry Program of NASA's Science Mission Directorate takes a direct approach to enhance student learning and engage the public in the latest research on meteorites, asteroids, planets, moons, and other materials in our Solar System with the website known as PSRD. The Planetary Science Research Discoveries (PSRD) website at www.psrd.hawaii.edu explores the science questions that researchers are actively pursuing about our Solar System and explains how the answers are discovered and what they mean. The site helps to convey the scientific basis for sample study to the broader scientific community and the excitement of new results in cosmochemistry to the general public. We share with our broad audience the fascinating discoveries made by cosmochemists, increasing public awareness of the value of sample-focused research in particular and of fundamental scientific research and space exploration in general. The scope of the website covers the full range of cosmochemical research and highlights the investigations of extraterrestrial materials that are used to better understand the origin of the Solar System and the processes by which planets, moons, and small bodies evolve. We relate the research to broader planetary science themes and mission results. Articles are categorized into: asteroids, comets, Earth, instruments of cosmochemistry, Jupiter system, Mars, Mars life issues, Mercury, meteorites, Moon, origins, and space weathering. PSRD articles are based on peer-reviewed, journal publications. Some PSRD articles are based on more than one published paper in order to present multiple views and outcomes of research on a topic of interest. To date, 150 PSRD articles have been based on 184 journal articles (and counting) written by some of the most active cosmochemists and planetary scientists