WorldWideScience

Sample records for link discovery approaches

  1. 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

  2. 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…

  3. 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...

  4. Net present value approaches for drug discovery.

    Science.gov (United States)

    Svennebring, Andreas M; Wikberg, Jarl Es

    2013-12-01

    Three dedicated approaches to the calculation of the risk-adjusted net present value (rNPV) in drug discovery projects under different assumptions are suggested. The probability of finding a candidate drug suitable for clinical development and the time to the initiation of the clinical development is assumed to be flexible in contrast to the previously used models. The rNPV of the post-discovery cash flows is calculated as the probability weighted average of the rNPV at each potential time of initiation of clinical development. Practical considerations how to set probability rates, in particular during the initiation and termination of a project is discussed.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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 ...

  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. Semantic Approaches for Knowledge Discovery and Retrieval in Biomedicine

    DEFF Research Database (Denmark)

    Wilkowski, Bartlomiej

    This thesis discusses potential applications of semantics to the recent literaturebased informatics systems to facilitate knowledge discovery, hypothesis generation, and literature retrieval in the domain of biomedicine. The approaches presented herein make use of semantic information extracted...

  12. 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.

  13. 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.

  14. 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.

  15. "Structured Discovery": A Modified Inquiry Approach to Teaching Social Studies.

    Science.gov (United States)

    Lordon, John

    1981-01-01

    Describes structured discovery approach to inquiry teaching which encourages the teacher to select instructional objectives, content, and questions to be answered. The focus is on individual and group activities. A brief outline using this approach to analyze Adolf Hitler is presented. (KC)

  16. Symbiosis-inspired approaches to antibiotic discovery.

    Science.gov (United States)

    Adnani, Navid; Rajski, Scott R; Bugni, Tim S

    2017-07-06

    Covering: 2010 up to 2017Life on Earth is characterized by a remarkable abundance of symbiotic and highly refined relationships among life forms. Defined as any kind of close, long-term association between two organisms, symbioses can be mutualistic, commensalistic or parasitic. Historically speaking, selective pressures have shaped symbioses in which one organism (typically a bacterium or fungus) generates bioactive small molecules that impact the host (and possibly other symbionts); the symbiosis is driven fundamentally by the genetic machineries available to the small molecule producer. The human microbiome is now integral to the most recent chapter in animal-microbe symbiosis studies and plant-microbe symbioses have significantly advanced our understanding of natural products biosynthesis; this also is the case for studies of fungal-microbe symbioses. However, much less is known about microbe-microbe systems involving interspecies interactions. Microbe-derived small molecules (i.e. antibiotics and quorum sensing molecules, etc.) have been shown to regulate transcription in microbes within the same environmental niche, suggesting interspecies interactions whereas, intraspecies interactions, such as those that exploit autoinducing small molecules, also modulate gene expression based on environmental cues. We, and others, contend that symbioses provide almost unlimited opportunities for the discovery of new bioactive compounds whose activities and applications have been evolutionarily optimized. Particularly intriguing is the possibility that environmental effectors can guide laboratory expression of secondary metabolites from "orphan", or silent, biosynthetic gene clusters (BGCs). Notably, many of the studies summarized here result from advances in "omics" technologies and highlight how symbioses have given rise to new anti-bacterial and antifungal natural products now being discovered.

  17. 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 ...

  18. 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.

  19. Semantic Search in E-Discovery: An Interdisciplinary Approach

    NARCIS (Netherlands)

    Graus, D.; Ren, Z.; de Rijke, M.; van Dijk, D.; Henseler, H.; van der Knaap, N.

    2013-01-01

    We propose an interdisciplinary approach to applying and evaluating semantic search in the e-discovery setting. By combining expertise from the fields of law and criminology with that of information retrieval and extraction, we move beyond "algorithm-centric" evaluation, towards evaluating the

  20. Hierarchical virtual screening approaches in small molecule drug discovery.

    Science.gov (United States)

    Kumar, Ashutosh; Zhang, Kam Y J

    2015-01-01

    Virtual screening has played a significant role in the discovery of small molecule inhibitors of therapeutic targets in last two decades. Various ligand and structure-based virtual screening approaches are employed to identify small molecule ligands for proteins of interest. These approaches are often combined in either hierarchical or parallel manner to take advantage of the strength and avoid the limitations associated with individual methods. Hierarchical combination of ligand and structure-based virtual screening approaches has received noteworthy success in numerous drug discovery campaigns. In hierarchical virtual screening, several filters using ligand and structure-based approaches are sequentially applied to reduce a large screening library to a number small enough for experimental testing. In this review, we focus on different hierarchical virtual screening strategies and their application in the discovery of small molecule modulators of important drug targets. Several virtual screening studies are discussed to demonstrate the successful application of hierarchical virtual screening in small molecule drug discovery. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. CLARM: An integrative approach for functional modules discovery

    KAUST Repository

    Salem, Saeed M.; Alroobi, Rami; Banitaan, Shadi; Seridi, Loqmane; Brewer, James E.; Aljarah, Ibrahim

    2011-01-01

    Functional module discovery aims to find well-connected subnetworks which can serve as candidate protein complexes. Advances in High-throughput proteomic technologies have enabled the collection of large amount of interaction data as well as gene expression data. We propose, CLARM, a clustering algorithm that integrates gene expression profiles and protein protein interaction network for biological modules discovery. The main premise is that by enriching the interaction network by adding interactions between genes which are highly co-expressed over a wide range of biological and environmental conditions, we can improve the quality of the discovered modules. Protein protein interactions, known protein complexes, and gene expression profiles for diverse environmental conditions from the yeast Saccharomyces cerevisiae were used for evaluate the biological significance of the reported modules. Our experiments show that the CLARM approach is competitive to wellestablished module discovery methods. Copyright © 2011 ACM.

  2. A new approach to the rationale discovery of polymeric biomaterials

    Science.gov (United States)

    Kohn, Joachim; Welsh, William J.; Knight, Doyle

    2007-01-01

    This paper attempts to illustrate both the need for new approaches to biomaterials discovery as well as the significant promise inherent in the use of combinatorial and computational design strategies. The key observation of this Leading Opinion Paper is that the biomaterials community has been slow to embrace advanced biomaterials discovery tools such as combinatorial methods, high throughput experimentation, and computational modeling in spite of the significant promise shown by these discovery tools in materials science, medicinal chemistry and the pharmaceutical industry. It seems that the complexity of living cells and their interactions with biomaterials has been a conceptual as well as a practical barrier to the use of advanced discovery tools in biomaterials science. However, with the continued increase in computer power, the goal of predicting the biological response of cells in contact with biomaterials surfaces is within reach. Once combinatorial synthesis, high throughput experimentation, and computational modeling are integrated into the biomaterials discovery process, a significant acceleration is possible in the pace of development of improved medical implants, tissue regeneration scaffolds, and gene/drug delivery systems. PMID:17644176

  3. A collaborative filtering-based approach to biomedical knowledge discovery.

    Science.gov (United States)

    Lever, Jake; Gakkhar, Sitanshu; Gottlieb, Michael; Rashnavadi, Tahereh; Lin, Santina; Siu, Celia; Smith, Maia; Jones, Martin R; Krzywinski, Martin; Jones, Steven J M; Wren, Jonathan

    2018-02-15

    The increase in publication rates makes it challenging for an individual researcher to stay abreast of all relevant research in order to find novel research hypotheses. Literature-based discovery methods make use of knowledge graphs built using text mining and can infer future associations between biomedical concepts that will likely occur in new publications. These predictions are a valuable resource for researchers to explore a research topic. Current methods for prediction are based on the local structure of the knowledge graph. A method that uses global knowledge from across the knowledge graph needs to be developed in order to make knowledge discovery a frequently used tool by researchers. We propose an approach based on the singular value decomposition (SVD) that is able to combine data from across the knowledge graph through a reduced representation. Using cooccurrence data extracted from published literature, we show that SVD performs better than the leading methods for scoring discoveries. We also show the diminishing predictive power of knowledge discovery as we compare our predictions with real associations that appear further into the future. Finally, we examine the strengths and weaknesses of the SVD approach against another well-performing system using several predicted associations. All code and results files for this analysis can be accessed at https://github.com/jakelever/knowledgediscovery. sjones@bcgsc.ca. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  4. Fragment approaches in structure-based drug discovery

    International Nuclear Information System (INIS)

    Hubbard, Roderick E.

    2008-01-01

    Fragment-based methods are successfully generating novel and selective drug-like inhibitors of protein targets, with a number of groups reporting compounds entering clinical trials. This paper summarizes the key features of the approach as one of the tools in structure-guided drug discovery. There has been considerable interest recently in what is known as 'fragment-based lead discovery'. The novel feature of the approach is to begin with small low-affinity compounds. The main advantage is that a larger potential chemical diversity can be sampled with fewer compounds, which is particularly important for new target classes. The approach relies on careful design of the fragment library, a method that can detect binding of the fragment to the protein target, determination of the structure of the fragment bound to the target, and the conventional use of structural information to guide compound optimization. In this article the methods are reviewed, and experiences in fragment-based discovery of lead series of compounds against kinases such as PDK1 and ATPases such as Hsp90 are discussed. The examples illustrate some of the key benefits and issues of the approach and also provide anecdotal examples of the patterns seen in selectivity and the binding mode of fragments across different protein targets

  5. 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.

  6. Development of Scientific Approach Based on Discovery Learning Module

    Science.gov (United States)

    Ellizar, E.; Hardeli, H.; Beltris, S.; Suharni, R.

    2018-04-01

    Scientific Approach is a learning process, designed to make the students actively construct their own knowledge through stages of scientific method. The scientific approach in learning process can be done by using learning modules. One of the learning model is discovery based learning. Discovery learning is a learning model for the valuable things in learning through various activities, such as observation, experience, and reasoning. In fact, the students’ activity to construct their own knowledge were not optimal. It’s because the available learning modules were not in line with the scientific approach. The purpose of this study was to develop a scientific approach discovery based learning module on Acid Based, also on electrolyte and non-electrolyte solution. The developing process of this chemistry modules use the Plomp Model with three main stages. The stages are preliminary research, prototyping stage, and the assessment stage. The subject of this research was the 10th and 11th Grade of Senior High School students (SMAN 2 Padang). Validation were tested by the experts of Chemistry lecturers and teachers. Practicality of these modules had been tested through questionnaire. The effectiveness had been tested through experimental procedure by comparing student achievement between experiment and control groups. Based on the findings, it can be concluded that the developed scientific approach discovery based learning module significantly improve the students’ learning in Acid-based and Electrolyte solution. The result of the data analysis indicated that the chemistry module was valid in content, construct, and presentation. Chemistry module also has a good practicality level and also accordance with the available time. This chemistry module was also effective, because it can help the students to understand the content of the learning material. That’s proved by the result of learning student. Based on the result can conclude that chemistry module based on

  7. 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

  8. 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.

  9. AN INTEGRATED APPROACH FOR LINKED DATA BROWSING

    Directory of Open Access Journals (Sweden)

    W. Beek

    2017-07-01

    Full Text Available The Netherlands' Cadastre, Land Registry and Mapping Agency – in short Kadaster – collects and registers administrative and spatial data on property and the rights involved. Currently, the Kadaster is publishing its geo-spatial data assets as Linked Open Data. The Kadaster manages hundreds of datasets that describe hundreds of millions of geospatial objects, including all Dutch buildings, roads, and forests. The Kadaster exposes this large collection of data to thousands of daily users that operate from within different contexts and that need to be supported in different use cases. Therefore, Kadaster must offer diverse, yet complementary, approaches for browsing and exploring the data it publishes. Specifically, it supports the following paradigms for browsing and exploring its data assets: hierarchical browsing, graph navigation, faceted browsing, and tabular browsing. These paradigms are useful for different tasks, cover different use cases, and are implemented by reusing and/or developing Open Source libraries and applications.

  10. Discovery of Boolean metabolic networks: integer linear programming based approach.

    Science.gov (United States)

    Qiu, Yushan; Jiang, Hao; Ching, Wai-Ki; Cheng, Xiaoqing

    2018-04-11

    Traditional drug discovery methods focused on the efficacy of drugs rather than their toxicity. However, toxicity and/or lack of efficacy are produced when unintended targets are affected in metabolic networks. Thus, identification of biological targets which can be manipulated to produce the desired effect with minimum side-effects has become an important and challenging topic. Efficient computational methods are required to identify the drug targets while incurring minimal side-effects. In this paper, we propose a graph-based computational damage model that summarizes the impact of enzymes on compounds in metabolic networks. An efficient method based on Integer Linear Programming formalism is then developed to identify the optimal enzyme-combination so as to minimize the side-effects. The identified target enzymes for known successful drugs are then verified by comparing the results with those in the existing literature. Side-effects reduction plays a crucial role in the study of drug development. A graph-based computational damage model is proposed and the theoretical analysis states the captured problem is NP-completeness. The proposed approaches can therefore contribute to the discovery of drug targets. Our developed software is available at " http://hkumath.hku.hk/~wkc/APBC2018-metabolic-network.zip ".

  11. Network-based approaches to climate knowledge discovery

    Science.gov (United States)

    Budich, Reinhard; Nyberg, Per; Weigel, Tobias

    2011-11-01

    Climate Knowledge Discovery Workshop; Hamburg, Germany, 30 March to 1 April 2011 Do complex networks combined with semantic Web technologies offer the next generation of solutions in climate science? To address this question, a first Climate Knowledge Discovery (CKD) Workshop, hosted by the German Climate Computing Center (Deutsches Klimarechenzentrum (DKRZ)), brought together climate and computer scientists from major American and European laboratories, data centers, and universities, as well as representatives from industry, the broader academic community, and the semantic Web communities. The participants, representing six countries, were concerned with large-scale Earth system modeling and computational data analysis. The motivation for the meeting was the growing problem that climate scientists generate data faster than it can be interpreted and the need to prepare for further exponential data increases. Current analysis approaches are focused primarily on traditional methods, which are best suited for large-scale phenomena and coarse-resolution data sets. The workshop focused on the open discussion of ideas and technologies to provide the next generation of solutions to cope with the increasing data volumes in climate science.

  12. A novel time series link prediction method: Learning automata approach

    Science.gov (United States)

    Moradabadi, Behnaz; Meybodi, Mohammad Reza

    2017-09-01

    Link prediction is a main social network challenge that uses the network structure to predict future links. The common link prediction approaches to predict hidden links use a static graph representation where a snapshot of the network is analyzed to find hidden or future links. For example, similarity metric based link predictions are a common traditional approach that calculates the similarity metric for each non-connected link and sort the links based on their similarity metrics and label the links with higher similarity scores as the future links. Because people activities in social networks are dynamic and uncertainty, and the structure of the networks changes over time, using deterministic graphs for modeling and analysis of the social network may not be appropriate. In the time-series link prediction problem, the time series link occurrences are used to predict the future links In this paper, we propose a new time series link prediction based on learning automata. In the proposed algorithm for each link that must be predicted there is one learning automaton and each learning automaton tries to predict the existence or non-existence of the corresponding link. To predict the link occurrence in time T, there is a chain consists of stages 1 through T - 1 and the learning automaton passes from these stages to learn the existence or non-existence of the corresponding link. Our preliminary link prediction experiments with co-authorship and email networks have provided satisfactory results when time series link occurrences are considered.

  13. Hacking 360 Link: A hybrid approach

    Directory of Open Access Journals (Sweden)

    John Durno

    2012-10-01

    Full Text Available When the University of Victoria Libraries switched from a locally-hosted link resolver (SFX to a vendor-hosted link resolver (360Link, new strategies were required to effectively integrate the vendor-hosted link resolver with the Libraries' other systems and services. Custom javascript is used to add links to the 360Link page; these links then point at local PHP code running on UVic servers, which can then redirect to appropriate local service or display a form directly. An open source PHP OpenURL parser class is announced. Consideration is given to the importance of maintaining open protocols and standards in the transition to vendor-hosted services.

  14. 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

  15. 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).

  16. Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.

    Science.gov (United States)

    Neumann, Heinz; Neumann-Staubitz, Petra

    2010-06-01

    Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology.

  17. Rationale for a natural products approach to herbicide discovery.

    Science.gov (United States)

    Dayan, Franck E; Owens, Daniel K; Duke, Stephen O

    2012-04-01

    Weeds continue to evolve resistance to all the known modes of herbicidal action, but no herbicide with a new target site has been commercialized in nearly 20 years. The so-called 'new chemistries' are simply molecules belonging to new chemical classes that have the same mechanisms of action as older herbicides (e.g. the protoporphyrinogen-oxidase-inhibiting pyrimidinedione saflufenacil or the very-long-chain fatty acid elongase targeting sulfonylisoxazoline herbicide pyroxasulfone). Therefore, the number of tools to manage weeds, and in particular those that can control herbicide-resistant weeds, is diminishing rapidly. There is an imminent need for truly innovative classes of herbicides that explore chemical spaces and interact with target sites not previously exploited by older active ingredients. This review proposes a rationale for a natural-products-centered approach to herbicide discovery that capitalizes on the structural diversity and ingenuity afforded by these biologically active compounds. The natural process of extended-throughput screening (high number of compounds tested on many potential target sites over long periods of times) that has shaped the evolution of natural products tends to generate molecules tailored to interact with specific target sites. As this review shows, there is generally little overlap between the mode of action of natural and synthetic phytotoxins, and more emphasis should be placed on applying methods that have proved beneficial to the pharmaceutical industry to solve problems in the agrochemical industry. Published 2012 by John Wiley & Sons, Ltd.

  18. A Wavelet-Based Approach to Pattern Discovery in Melodies

    DEFF Research Database (Denmark)

    Velarde, Gissel; Meredith, David; Weyde, Tillman

    2016-01-01

    We present a computational method for pattern discovery based on the application of the wavelet transform to symbolic representations of melodies or monophonic voices. We model the importance of a discovered pattern in terms of the compression ratio that can be achieved by using it to describe...

  19. Computational and Experimental Approaches to Cancer Biomarker Discovery

    DEFF Research Database (Denmark)

    Krzystanek, Marcin

    of a patient’s response to a particular treatment, thus helping to avoid unnecessary treatment and unwanted side effects in non-responding individuals.Currently biomarker discovery is facilitated by recent advances in high-throughput technologies when association between a given biological phenotype...... and the state or level of a large number of molecular entities is investigated. Such associative analysis could be confounded by several factors, leading to false discoveries. For example, it is assumed that with the exception of the true biomarkers most molecular entities such as gene expression levels show...... random distribution in a given cohort. However, gene expression levels may also be affected by technical bias when the actual measurement technology or sample handling may introduce a systematic error. If the distribution of systematic errors correlates with the biological phenotype then the risk...

  20. 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.

  1. Proteomic Approaches in Biomarker Discovery: New Perspectives in Cancer Diagnostics

    Science.gov (United States)

    Kocevar, Nina; Komel, Radovan

    2014-01-01

    Despite remarkable progress in proteomic methods, including improved detection limits and sensitivity, these methods have not yet been established in routine clinical practice. The main limitations, which prevent their integration into clinics, are high cost of equipment, the need for highly trained personnel, and last, but not least, the establishment of reliable and accurate protein biomarkers or panels of protein biomarkers for detection of neoplasms. Furthermore, the complexity and heterogeneity of most solid tumours present obstacles in the discovery of specific protein signatures, which could be used for early detection of cancers, for prediction of disease outcome, and for determining the response to specific therapies. However, cancer proteome, as the end-point of pathological processes that underlie cancer development and progression, could represent an important source for the discovery of new biomarkers and molecular targets for tailored therapies. PMID:24550697

  2. Integrated analytical approaches towards toxic algal natural products discovery

    DEFF Research Database (Denmark)

    Larsen, Thomas Ostenfeld; Rasmussen, Silas Anselm; Gedsted Andersen, Mikael

    Microalgae are known to produce toxins which affect the marine ecosystems. This include compounds active against competitors, grazers and in many cases also fish (1,2). Many strategies can be followed for discovery of novel bioactive secondary metabolites from marine sources. We have previously...... is dereplication, where we use explorative solid-phase extraction (E-SPE), and UHPLC-state-of-the-art high resolution mass spectrometry (waste time isolating and elucidating...

  3. 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...

  4. 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

  5. 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.

  6. Stem cells and the pancreas: from discovery to clinical approach

    Directory of Open Access Journals (Sweden)

    Angelica Dessì

    2016-02-01

    Full Text Available The existence of stem cells within the adult pancreas is supported by the ability of this organ to regenerate its endocrine component in various conditions such as pregnancy and following partial pancreatectomy. Several studies have shown that progenitor or adult stem cells may reside within the pancreas and particularly in the pancreatic ducts, including acinar cells and islets of Langerhans. The discovery of human pluripotent stem cells in the pancreas, and the possibility of development of strategies for generating these, represented a turning point for the therapeutic interventions of type 1 diabetes.Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  7. Linking Data and Publications: Towards a Cross-Disciplinary Approach

    Directory of Open Access Journals (Sweden)

    Maarten Hoogerwerf

    2013-06-01

    Full Text Available In this paper, we tackle the challenge of linking scholarly information in multi-disciplinary research infrastructures. There is a trend towards linking publications with research data and other information, but, as it is still emerging, this is handled differently by various initiatives and disciplines. For OpenAIRE, a European cross-disciplinary publication infrastructure, this poses the challenge of supporting these heterogeneous practices. Hence, OpenAIRE wants to contribute to the development of a common approach for discipline-independent linking practices between publications, data, project information and researchers. To this end, we constructed two demonstrators to identify commonalities and differences. The results show the importance of stable and unique identifiers, and support a ‘by reference’ approach of interlinking research results. This approach allows discipline-specific research information to be managed independently in distributed systems and avoids redundant maintenance. Furthermore, it allows these disciplinary systems to manage the specialized structures of their contents themselves.

  8. 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

  9. Mass spectrometric based approaches in urine metabolomics and biomarker discovery.

    Science.gov (United States)

    Khamis, Mona M; Adamko, Darryl J; El-Aneed, Anas

    2017-03-01

    Urine metabolomics has recently emerged as a prominent field for the discovery of non-invasive biomarkers that can detect subtle metabolic discrepancies in response to a specific disease or therapeutic intervention. Urine, compared to other biofluids, is characterized by its ease of collection, richness in metabolites and its ability to reflect imbalances of all biochemical pathways within the body. Following urine collection for metabolomic analysis, samples must be immediately frozen to quench any biogenic and/or non-biogenic chemical reactions. According to the aim of the experiment; sample preparation can vary from simple procedures such as filtration to more specific extraction protocols such as liquid-liquid extraction. Due to the lack of comprehensive studies on urine metabolome stability, higher storage temperatures (i.e. 4°C) and repetitive freeze-thaw cycles should be avoided. To date, among all analytical techniques, mass spectrometry (MS) provides the best sensitivity, selectivity and identification capabilities to analyze the majority of the metabolite composition in the urine. Combined with the qualitative and quantitative capabilities of MS, and due to the continuous improvements in its related technologies (i.e. ultra high-performance liquid chromatography [UPLC] and hydrophilic interaction liquid chromatography [HILIC]), liquid chromatography (LC)-MS is unequivocally the most utilized and the most informative analytical tool employed in urine metabolomics. Furthermore, differential isotope tagging techniques has provided a solution to ion suppression from urine matrix thus allowing for quantitative analysis. In addition to LC-MS, other MS-based technologies have been utilized in urine metabolomics. These include direct injection (infusion)-MS, capillary electrophoresis-MS and gas chromatography-MS. In this article, the current progresses of different MS-based techniques in exploring the urine metabolome as well as the recent findings in providing

  10. A hybrid linked data approach to support asset management

    NARCIS (Netherlands)

    Luiten, G.T.; Bohms, H.M.; O'Keeffe, A.; Nederveen, S. van; Bakker, J.; Wikstrom, L.

    2016-01-01

    This paper evaluates experiences with applying a linked data approach for coping with the many challenges for information management in asset management from the perspective of National Road Authorities (NRAs). As influential players, NRAs are often the initiators of innovation in the civil

  11. 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.

  12. Content Discovery from Composite Audio : An unsupervised approach

    NARCIS (Netherlands)

    Lu, L.

    2009-01-01

    In this thesis, we developed and assessed a novel robust and unsupervised framework for semantic inference from composite audio signals. We focused on the problem of detecting audio scenes and grouping them into meaningful clusters. Our approach addressed all major steps in a general process of

  13. A genetic programming approach for Burkholderia Pseudomallei diagnostic pattern discovery

    Science.gov (United States)

    Yang, Zheng Rong; Lertmemongkolchai, Ganjana; Tan, Gladys; Felgner, Philip L.; Titball, Richard

    2009-01-01

    Motivation: Finding diagnostic patterns for fighting diseases like Burkholderia pseudomallei using biomarkers involves two key issues. First, exhausting all subsets of testable biomarkers (antigens in this context) to find a best one is computationally infeasible. Therefore, a proper optimization approach like evolutionary computation should be investigated. Second, a properly selected function of the antigens as the diagnostic pattern which is commonly unknown is a key to the diagnostic accuracy and the diagnostic effectiveness in clinical use. Results: A conversion function is proposed to convert serum tests of antigens on patients to binary values based on which Boolean functions as the diagnostic patterns are developed. A genetic programming approach is designed for optimizing the diagnostic patterns in terms of their accuracy and effectiveness. During optimization, it is aimed to maximize the coverage (the rate of positive response to antigens) in the infected patients and minimize the coverage in the non-infected patients while maintaining the fewest number of testable antigens used in the Boolean functions as possible. The final coverage in the infected patients is 96.55% using 17 of 215 (7.4%) antigens with zero coverage in the non-infected patients. Among these 17 antigens, BPSL2697 is the most frequently selected one for the diagnosis of Burkholderia Pseudomallei. The approach has been evaluated using both the cross-validation and the Jack–knife simulation methods with the prediction accuracy as 93% and 92%, respectively. A novel approach is also proposed in this study to evaluate a model with binary data using ROC analysis. Contact: z.r.yang@ex.ac.uk PMID:19561021

  14. 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.

  15. Biomarker discovery in neurological diseases: a metabolomic approach

    Directory of Open Access Journals (Sweden)

    Afaf El-Ansary

    2009-12-01

    Full Text Available Afaf El-Ansary, Nouf Al-Afaleg, Yousra Al-YafaeeBiochemistry Department, Science College, King Saud University, Riyadh, Saudi ArabiaAbstract: Biomarkers are pharmacological and physiological measurements or specific biochemicals in the body that have a particular molecular feature that makes them useful for measuring the progress of disease or the effects of treatment. Due to the complexity of neurological disorders, it is very difficult to have perfect markers. Brain diseases require plenty of markers to reflect the metabolic impairment of different brain cells. The recent introduction of the metabolomic approach helps the study of neurological diseases based on profiling a multitude of biochemical components related to brain metabolism. This review is a trial to elucidate the possibility to use this approach to identify plasma metabolic markers related to neurological disorders. Previous trials using different metabolomic analyses including nuclear magnetic resonance spectroscopy, gas chromatography combined with mass spectrometry, liquid chromatography combined with mass spectrometry, and capillary electrophoresis will be traced.Keywords: metabolic biomarkers, neurological disorders. metabolome, nuclear magnetic resonance, mass spectrometry, chromatography

  16. Discovery and Development of ATP-Competitive mTOR Inhibitors Using Computational Approaches.

    Science.gov (United States)

    Luo, Yao; Wang, Ling

    2017-11-16

    The mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism, and angiogenesis. This protein is an attractive target for new anticancer drug development. Significant progress has been made in hit discovery, lead optimization, drug candidate development and determination of the three-dimensional (3D) structure of mTOR. Computational methods have been applied to accelerate the discovery and development of mTOR inhibitors helping to model the structure of mTOR, screen compound databases, uncover structure-activity relationship (SAR) and optimize the hits, mine the privileged fragments and design focused libraries. Besides, computational approaches were also applied to study protein-ligand interactions mechanisms and in natural product-driven drug discovery. Herein, we survey the most recent progress on the application of computational approaches to advance the discovery and development of compounds targeting mTOR. Future directions in the discovery of new mTOR inhibitors using computational methods are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Analysis student self efficacy in terms of using Discovery Learning model with SAVI approach

    Science.gov (United States)

    Sahara, Rifki; Mardiyana, S., Dewi Retno Sari

    2017-12-01

    Often students are unable to prove their academic achievement optimally according to their abilities. One reason is that they often feel unsure that they are capable of completing the tasks assigned to them. For students, such beliefs are necessary. The term belief has called self efficacy. Self efficacy is not something that has brought about by birth or something with permanent quality of an individual, but is the result of cognitive processes, the meaning one's self efficacy will be stimulated through learning activities. Self efficacy has developed and enhanced by a learning model that can stimulate students to foster confidence in their capabilities. One of them is by using Discovery Learning model with SAVI approach. Discovery Learning model with SAVI approach is one of learning models that involves the active participation of students in exploring and discovering their own knowledge and using it in problem solving by utilizing all the sensory devices they have. This naturalistic qualitative research aims to analyze student self efficacy in terms of use the Discovery Learning model with SAVI approach. The subjects of this study are 30 students focused on eight students who have high, medium, and low self efficacy obtained through purposive sampling technique. The data analysis of this research used three stages, that were reducing, displaying, and getting conclusion of the data. Based on the results of data analysis, it was concluded that the self efficacy appeared dominantly on the learning by using Discovery Learning model with SAVI approach is magnitude dimension.

  18. 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.

  19. New approaches to e-reserve linking, sharing and streaming

    CERN Document Server

    Cheung, Ophelia; Patrick, Susan

    2010-01-01

    Aimed at academic library practitioners, this book describes how e-reserve services can evolve and adapt to the changing virtual learning environment of higher education. New approaches discussed include: the integration of subscribed, free, and copyrighted resources within course management systems; innovative employment of open URL link resolvers to connect e-reserve with library e-resources and services; video streaming within course documents; and the creative use of bibliographic software to produce customized reading lists. New Approaches to E-Reserve includes detailed descriptions and e

  20. 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.

  1. 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

  2. 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.

  3. Understanding price discovery in interconnected markets: Generalized Langevin process approach and simulation

    Science.gov (United States)

    Schenck, Natalya A.; Horvath, Philip A.; Sinha, Amit K.

    2018-02-01

    While the literature on price discovery process and information flow between dominant and satellite market is exhaustive, most studies have applied an approach that can be traced back to Hasbrouck (1995) or Gonzalo and Granger (1995). In this paper, however, we propose a Generalized Langevin process with asymmetric double-well potential function, with co-integrated time series and interconnected diffusion processes to model the information flow and price discovery process in two, a dominant and a satellite, interconnected markets. A simulated illustration of the model is also provided.

  4. Deep-Sea Microbes: Linking Biogeochemical Rates to -Omics Approaches

    Science.gov (United States)

    Herndl, G. J.; Sintes, E.; Bayer, B.; Bergauer, K.; Amano, C.; Hansman, R.; Garcia, J.; Reinthaler, T.

    2016-02-01

    Over the past decade substantial progress has been made in determining deep ocean microbial activity and resolving some of the enigmas in understanding the deep ocean carbon flux. Also, metagenomics approaches have shed light onto the dark ocean's microbes but linking -omics approaches to biogeochemical rate measurements are generally rare in microbial oceanography and even more so for the deep ocean. In this presentation, we will show by combining metagenomics, -proteomics and biogeochemical rate measurements on the bulk and single-cell level that deep-sea microbes exhibit characteristics of generalists with a large genome repertoire, versatile in utilizing substrate as revealed by metaproteomics. This is in striking contrast with the apparently rather uniform dissolved organic matter pool in the deep ocean. Combining the different -omics approaches with metabolic rate measurements, we will highlight some major inconsistencies and enigmas in our understanding of the carbon cycling and microbial food web structure in the dark ocean.

  5. 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.

  6. 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

  7. Argo_CUDA: Exhaustive GPU based approach for motif discovery in large DNA datasets.

    Science.gov (United States)

    Vishnevsky, Oleg V; Bocharnikov, Andrey V; Kolchanov, Nikolay A

    2018-02-01

    The development of chromatin immunoprecipitation sequencing (ChIP-seq) technology has revolutionized the genetic analysis of the basic mechanisms underlying transcription regulation and led to accumulation of information about a huge amount of DNA sequences. There are a lot of web services which are currently available for de novo motif discovery in datasets containing information about DNA/protein binding. An enormous motif diversity makes their finding challenging. In order to avoid the difficulties, researchers use different stochastic approaches. Unfortunately, the efficiency of the motif discovery programs dramatically declines with the query set size increase. This leads to the fact that only a fraction of top "peak" ChIP-Seq segments can be analyzed or the area of analysis should be narrowed. Thus, the motif discovery in massive datasets remains a challenging issue. Argo_Compute Unified Device Architecture (CUDA) web service is designed to process the massive DNA data. It is a program for the detection of degenerate oligonucleotide motifs of fixed length written in 15-letter IUPAC code. Argo_CUDA is a full-exhaustive approach based on the high-performance GPU technologies. Compared with the existing motif discovery web services, Argo_CUDA shows good prediction quality on simulated sets. The analysis of ChIP-Seq sequences revealed the motifs which correspond to known transcription factor binding sites.

  8. Approach to Cerebrospinal Fluid (CSF) Biomarker Discovery and Evaluation in HIV Infection

    Energy Technology Data Exchange (ETDEWEB)

    Price, Richard W.; Peterson, Julia; Fuchs, Dietmar; Angel, Thomas E.; Zetterberg, Henrik; Hagberg, Lars; Spudich, Serena S.; Smith, Richard D.; Jacobs, Jon M.; Brown, Joseph N.; Gisslen, Magnus

    2013-12-13

    Central nervous system (CNS) infection is a nearly universal facet of systemic HIV infection that varies in character and neurological consequences. While clinical staging and neuropsychological test performance have been helpful in evaluating patients, cerebrospinal fluid (CSF) biomarkers present a valuable and objective approach to more accurate diagnosis, assessment of treatment effects and understanding of evolving pathobiology. We review some lessons from our recent experience with CSF biomarker studies. We have used two approaches to biomarker analysis: targeted, hypothesis-driven and non-targeted exploratory discovery methods. We illustrate the first with data from a cross-sectional study of defined subject groups across the spectrum of systemic and CNS disease progression and the second with a longitudinal study of the CSF proteome in subjects initiating antiretroviral treatment. Both approaches can be useful and, indeed, complementary. The first is helpful in assessing known or hypothesized biomarkers while the second can identify novel biomarkers and point to broad interactions in pathogenesis. Common to both is the need for well-defined samples and subjects that span a spectrum of biological activity and biomarker concentrations. Previouslydefined guide biomarkers of CNS infection, inflammation and neural injury are useful in categorizing samples for analysis and providing critical biological context for biomarker discovery studies. CSF biomarkers represent an underutilized but valuable approach to understanding the interactions of HIV and the CNS and to more objective diagnosis and assessment of disease activity. Both hypothesis-based and discovery methods can be useful in advancing the definition and use of these biomarkers.

  9. G-protein-coupled receptors: new approaches to maximise the impact of GPCRS in drug discovery.

    Science.gov (United States)

    Davey, John

    2004-04-01

    IBC's Drug Discovery Technology Series is a group of conferences highlighting technological advances and applications in niche areas of the drug discovery pipeline. This 2-day meeting focused on G-protein-coupled receptors (GPCRs), probably the most important and certainly the most valuable class of targets for drug discovery. The meeting was chaired by J Beesley (Vice President, European Business Development for LifeSpan Biosciences, Seattle, USA) and included 17 presentations on various aspects of GPCR activity, drug screens and therapeutic analyses. Keynote Addresses covered two of the emerging areas in GPCR regulation; receptor dimerisation (G Milligan, Professor of Molecular Pharmacology and Biochemistry, University of Glasgow, UK) and proteins that interact with GPCRs (J Bockaert, Laboratory of Functional Genomics, CNRS Montpellier, France). A third Keynote Address from W Thomsen (Director of GPCR Drug Screening, Arena Pharmaceuticals, USA) discussed Arena's general approach to drug discovery and illustrated this with reference to the development of an agonist with potential efficacy in Type II diabetes.

  10. 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.

  11. National Heart, Lung, and Blood Institute and the translation of cardiovascular discoveries into therapeutic approaches.

    Science.gov (United States)

    Galis, Zorina S; Black, Jodi B; Skarlatos, Sonia I

    2013-04-26

    The molecular causes of ≈4000 medical conditions have been described, yet only 5% have associated therapies. For decades, the average time for drug development through approval has taken 10 to 20 years. In recent years, the serious challenges that confront the private sector have made it difficult to capitalize on new opportunities presented by advances in genomics and cellular therapies. Current trends are disturbing. Pharmaceutical companies are reducing their investments in research, and biotechnology companies are struggling to obtain venture funds. To support early-stage translation of the discoveries in basic science, the National Institutes of Health and the National Heart, Lung, and Blood Institute have developed new approaches to facilitating the translation of basic discoveries into clinical applications and will continue to develop a variety of programs that create teams of academic investigators and industry partners. The goal of these programs is to maximize the public benefit of investment of taxpayer dollars in biomedical research and to lessen the risk required for industry partners to make substantial investments. This article highlights several examples of National Heart, Lung, and Blood Institute-initiated translational programs and National Institutes of Health translational resources designed to catalyze and enable the earliest stages of the biomedical product development process. The translation of latest discoveries into therapeutic approaches depends on continued federal funding to enhance the early stages of the product development process and to stimulate and catalyze partnerships between academia, industry, and other sources of capital.

  12. Approach to cerebrospinal fluid (CSF) biomarker discovery and evaluation in HIV infection.

    Science.gov (United States)

    Price, Richard W; Peterson, Julia; Fuchs, Dietmar; Angel, Thomas E; Zetterberg, Henrik; Hagberg, Lars; Spudich, Serena; Smith, Richard D; Jacobs, Jon M; Brown, Joseph N; Gisslen, Magnus

    2013-12-01

    Central nervous system (CNS) infection is a nearly universal facet of systemic HIV infection that varies in character and neurological consequences. While clinical staging and neuropsychological test performance have been helpful in evaluating patients, cerebrospinal fluid (CSF) biomarkers present a valuable and objective approach to more accurate diagnosis, assessment of treatment effects and understanding of evolving pathobiology. We review some lessons from our recent experience with CSF biomarker studies. We have used two approaches to biomarker analysis: targeted, hypothesis-driven and non-targeted exploratory discovery methods. We illustrate the first with data from a cross-sectional study of defined subject groups across the spectrum of systemic and CNS disease progression and the second with a longitudinal study of the CSF proteome in subjects initiating antiretroviral treatment. Both approaches can be useful and, indeed, complementary. The first is helpful in assessing known or hypothesized biomarkers while the second can identify novel biomarkers and point to broad interactions in pathogenesis. Common to both is the need for well-defined samples and subjects that span a spectrum of biological activity and biomarker concentrations. Previously-defined guide biomarkers of CNS infection, inflammation and neural injury are useful in categorizing samples for analysis and providing critical biological context for biomarker discovery studies. CSF biomarkers represent an underutilized but valuable approach to understanding the interactions of HIV and the CNS and to more objective diagnosis and assessment of disease activity. Both hypothesis-based and discovery methods can be useful in advancing the definition and use of these biomarkers.

  13. Renaissance in Antibiotic Discovery: Some Novel Approaches for Finding Drugs to Treat Bad Bugs.

    Science.gov (United States)

    Gadakh, Bharat; Van Aerschot, Arthur

    2015-01-01

    With the alarming resistance to currently used antibiotics, there is a serious worldwide threat to public health. Therefore, there is an urgent need to search for new antibiotics or new cellular targets which are essential for survival of the pathogens. However, during the past 50 years, only two new classes of antibiotics (oxazolidinone and lipopeptides) have reached the clinic. This suggests that the success rate in discovering new/novel antibiotics using conventional approaches is limited and that we must reconsider our antibiotic discovery approaches. While many new strategies are being pursued lately, this review primarily focuses only on a few of these novel/new approaches for antibiotic discovery. These include structure-based drug design (SBDD), the genomic approach, anti-virulence strategy, targeting nonmultiplying bacteria and the use of bacteriophages. In general, recent advancements in nuclear magnetic resonance, Xcrystallography, and genomic evolution have significant impact on antibacterial drug research. This review therefore aims to discuss recent strategies in searching new antibacterial agents making use of these technical novelties, their advantages, disadvantages and limitations.

  14. a Web Service Approach for Linking Sensors and Cellular Spaces

    Science.gov (United States)

    Isikdag, U.

    2013-09-01

    More and more devices are starting to be connected to the Internet. In the future the Internet will not only be a communication medium for people, it will in fact be a communication environment for devices. The connected devices which are also referred as Things will have an ability to interact with other devices over the Internet, i.) provide information in interoperable form and ii.) consume /utilize such information with the help of sensors embedded in them. This overall concept is known as Internet-of- Things (IoT). This requires new approaches to be investigated for system architectures to establish relations between spaces and sensors. The research presented in this paper elaborates on an architecture developed with this aim, i.e. linking spaces and sensors using a RESTful approach. The objective is making spaces aware of (sensor-embedded) devices, and making devices aware of spaces in a loosely coupled way (i.e. a state/usage/function change in the spaces would not have effect on sensors, similarly a location/state/usage/function change in sensors would not have any effect on spaces). The proposed architecture also enables the automatic assignment of sensors to spaces depending on space geometry and sensor location.

  15. Linking biomedical engineering ethics case study approach and policy.

    Science.gov (United States)

    Dibrell, William; Dobie, Elizabeth Ann

    2007-01-01

    In this paper we link bioengineering case study methods to the development of policy. The case study approach to ethics is an excellent way to show the complex nature of practical/moral reasoning. This approach can, however, lead to a kind of overwhelming complexity. The individual nature of each case makes it difficult to identify the most important information and difficult to see what moral considerations are most relevant. In order to make the overwhelming complexity less debilitating, we present a framework for moral decision making derived from suggestions made by W.D. Ross and Virginia Held. Ross articulates the multiple sources of morality and Held deepens the discussion by reminding us of the foundational importance of care and sympathy to our moral natures. We show how to use the notion of prima facie duty and discuss moral conflict. In doing this, we show how the framework, applied to cases, can be of assistance in helping us develop policies and codes of ethics with sufficient plasticity to be useful in the complex world of the bioengineer.

  16. Discovery of resources using MADM approaches for parallel and distributed computing

    Directory of Open Access Journals (Sweden)

    Mandeep Kaur

    2017-06-01

    Full Text Available Grid, a form of parallel and distributed computing, allows the sharing of data and computational resources among its users from various geographical locations. The grid resources are diverse in terms of their underlying attributes. The majority of the state-of-the-art resource discovery techniques rely on the static resource attributes during resource selection. However, the matching resources based on the static resource attributes may not be the most appropriate resources for the execution of user applications because they may have heavy job loads, less storage space or less working memory (RAM. Hence, there is a need to consider the current state of the resources in order to find the most suitable resources. In this paper, we have proposed a two-phased multi-attribute decision making (MADM approach for discovery of grid resources by using P2P formalism. The proposed approach considers multiple resource attributes for decision making of resource selection and provides the best suitable resource(s to grid users. The first phase describes a mechanism to discover all matching resources and applies SAW method to shortlist the top ranked resources, which are communicated to the requesting super-peer. The second phase of our proposed methodology applies integrated MADM approach (AHP enriched PROMETHEE-II on the list of selected resources received from different super-peers. The pairwise comparison of the resources with respect to their attributes is made and the rank of each resource is determined. The top ranked resource is then communicated to the grid user by the grid scheduler. Our proposed methodology enables the grid scheduler to allocate the most suitable resource to the user application and also reduces the search complexity by filtering out the less suitable resources during resource discovery.

  17. The Universe Discovery Guides: A Collaborative Approach to Educating with NASA Science

    Science.gov (United States)

    Manning, James G.; Lawton, Brandon L.; Gurton, Suzanne; Smith, Denise Anne; Schultz, Gregory; Astrophysics Community, NASA

    2015-08-01

    For the 2009 International Year of Astronomy, the then-existing NASA Origins Forum collaborated with the Astronomical Society of the Pacific (ASP) to create a series of monthly “Discovery Guides” for informal educator and amateur astronomer use in educating the public about featured sky objects and associated NASA science themes. Today’s NASA Astrophysics Science Education and Public Outreach Forum (SEPOF), one of the current generation of forums coordinating the work of NASA Science Mission Directorate (SMD) EPO efforts—in collaboration with the ASP and NASA SMD missions and programs--has adapted the Discovery Guides into “evergreen” educational resources suitable for a variety of audiences. The Guides focus on “deep sky” objects and astrophysics themes (stars and stellar evolution, galaxies and the universe, and exoplanets), showcasing EPO resources from more than 30 NASA astrophysics missions and programs in a coordinated and cohesive “big picture” approach across the electromagnetic spectrum, grounded in best practices to best serve the needs of the target audiences.Each monthly guide features a theme and a representative object well-placed for viewing, with an accompanying interpretive story, finding charts, strategies for conveying the topics, and complementary supporting NASA-approved education activities and background information from a spectrum of NASA missions and programs. The Universe Discovery Guides are downloadable from the NASA Night Sky Network web site at nightsky.jpl.nasa.gov and specifically from http://nightsky.jpl.nasa.gov/news-display.cfm?News_ID=611.The presentation will describe the collaborative’s experience in developing the guides, how they place individual science discoveries and learning resources into context for audiences, and how the Guides can be readily used in scientist public outreach efforts, in college and university introductory astronomy classes, and in other engagements between scientists, instructors

  18. 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

  19. Structure and organization of drug-target networks: insights from genomic approaches for drug discovery.

    Science.gov (United States)

    Janga, Sarath Chandra; Tzakos, Andreas

    2009-12-01

    Recent years have seen an explosion in the amount of "omics" data and the integration of several disciplines, which has influenced all areas of life sciences including that of drug discovery. Several lines of evidence now suggest that the traditional notion of "one drug-one protein" for one disease does not hold any more and that treatment for most complex diseases can best be attempted using polypharmacological approaches. In this review, we formalize the definition of a drug-target network by decomposing it into drug, target and disease spaces and provide an overview of our understanding in recent years about its structure and organizational principles. We discuss advances made in developing promiscuous drugs following the paradigm of polypharmacology and reveal their advantages over traditional drugs for targeting diseases such as cancer. We suggest that drug-target networks can be decomposed to be studied at a variety of levels and argue that such network-based approaches have important implications in understanding disease phenotypes and in accelerating drug discovery. We also discuss the potential and scope network pharmacology promises in harnessing the vast amount of data from high-throughput approaches for therapeutic advantage.

  20. Metabolic Network Discovery by Top-Down and Bottom-Up Approaches and Paths for Reconciliation

    Energy Technology Data Exchange (ETDEWEB)

    Çakır, Tunahan, E-mail: tcakir@gyte.edu.tr [Computational Systems Biology Group, Department of Bioengineering, Gebze Technical University (formerly known as Gebze Institute of Technology), Gebze (Turkey); Khatibipour, Mohammad Jafar [Computational Systems Biology Group, Department of Bioengineering, Gebze Technical University (formerly known as Gebze Institute of Technology), Gebze (Turkey); Department of Chemical Engineering, Gebze Technical University (formerly known as Gebze Institute of Technology), Gebze (Turkey)

    2014-12-03

    The primary focus in the network-centric analysis of cellular metabolism by systems biology approaches is to identify the active metabolic network for the condition of interest. Two major approaches are available for the discovery of the condition-specific metabolic networks. One approach starts from genome-scale metabolic networks, which cover all possible reactions known to occur in the related organism in a condition-independent manner, and applies methods such as the optimization-based Flux-Balance Analysis to elucidate the active network. The other approach starts from the condition-specific metabolome data, and processes the data with statistical or optimization-based methods to extract information content of the data such that the active network is inferred. These approaches, termed bottom-up and top-down, respectively, are currently employed independently. However, considering that both approaches have the same goal, they can both benefit from each other paving the way for the novel integrative analysis methods of metabolome data- and flux-analysis approaches in the post-genomic era. This study reviews the strengths of constraint-based analysis and network inference methods reported in the metabolic systems biology field; then elaborates on the potential paths to reconcile the two approaches to shed better light on how the metabolism functions.

  1. Metabolic Network Discovery by Top-Down and Bottom-Up Approaches and Paths for Reconciliation

    International Nuclear Information System (INIS)

    Çakır, Tunahan; Khatibipour, Mohammad Jafar

    2014-01-01

    The primary focus in the network-centric analysis of cellular metabolism by systems biology approaches is to identify the active metabolic network for the condition of interest. Two major approaches are available for the discovery of the condition-specific metabolic networks. One approach starts from genome-scale metabolic networks, which cover all possible reactions known to occur in the related organism in a condition-independent manner, and applies methods such as the optimization-based Flux-Balance Analysis to elucidate the active network. The other approach starts from the condition-specific metabolome data, and processes the data with statistical or optimization-based methods to extract information content of the data such that the active network is inferred. These approaches, termed bottom-up and top-down, respectively, are currently employed independently. However, considering that both approaches have the same goal, they can both benefit from each other paving the way for the novel integrative analysis methods of metabolome data- and flux-analysis approaches in the post-genomic era. This study reviews the strengths of constraint-based analysis and network inference methods reported in the metabolic systems biology field; then elaborates on the potential paths to reconcile the two approaches to shed better light on how the metabolism functions.

  2. Combinatorial pattern discovery approach for the folding trajectory analysis of a beta-hairpin.

    Directory of Open Access Journals (Sweden)

    Laxmi Parida

    2005-06-01

    Full Text Available The study of protein folding mechanisms continues to be one of the most challenging problems in computational biology. Currently, the protein folding mechanism is often characterized by calculating the free energy landscape versus various reaction coordinates, such as the fraction of native contacts, the radius of gyration, RMSD from the native structure, and so on. In this paper, we present a combinatorial pattern discovery approach toward understanding the global state changes during the folding process. This is a first step toward an unsupervised (and perhaps eventually automated approach toward identification of global states. The approach is based on computing biclusters (or patterned clusters-each cluster is a combination of various reaction coordinates, and its signature pattern facilitates the computation of the Z-score for the cluster. For this discovery process, we present an algorithm of time complexity c in RO((N + nm log n, where N is the size of the output patterns and (n x m is the size of the input with n time frames and m reaction coordinates. To date, this is the best time complexity for this problem. We next apply this to a beta-hairpin folding trajectory and demonstrate that this approach extracts crucial information about protein folding intermediate states and mechanism. We make three observations about the approach: (1 The method recovers states previously obtained by visually analyzing free energy surfaces. (2 It also succeeds in extracting meaningful patterns and structures that had been overlooked in previous works, which provides a better understanding of the folding mechanism of the beta-hairpin. These new patterns also interconnect various states in existing free energy surfaces versus different reaction coordinates. (3 The approach does not require calculating the free energy values, yet it offers an analysis comparable to, and sometimes better than, the methods that use free energy landscapes, thus validating the

  3. Combinatorial Pattern Discovery Approach for the Folding Trajectory Analysis of a beta-Hairpin.

    Directory of Open Access Journals (Sweden)

    2005-06-01

    Full Text Available The study of protein folding mechanisms continues to be one of the most challenging problems in computational biology. Currently, the protein folding mechanism is often characterized by calculating the free energy landscape versus various reaction coordinates, such as the fraction of native contacts, the radius of gyration, RMSD from the native structure, and so on. In this paper, we present a combinatorial pattern discovery approach toward understanding the global state changes during the folding process. This is a first step toward an unsupervised (and perhaps eventually automated approach toward identification of global states. The approach is based on computing biclusters (or patterned clusters-each cluster is a combination of various reaction coordinates, and its signature pattern facilitates the computation of the Z-score for the cluster. For this discovery process, we present an algorithm of time complexity cinRO((N + nm log n, where N is the size of the output patterns and (n x m is the size of the input with n time frames and m reaction coordinates. To date, this is the best time complexity for this problem. We next apply this to a beta-hairpin folding trajectory and demonstrate that this approach extracts crucial information about protein folding intermediate states and mechanism. We make three observations about the approach: (1 The method recovers states previously obtained by visually analyzing free energy surfaces. (2 It also succeeds in extracting meaningful patterns and structures that had been overlooked in previous works, which provides a better understanding of the folding mechanism of the beta-hairpin. These new patterns also interconnect various states in existing free energy surfaces versus different reaction coordinates. (3 The approach does not require calculating the free energy values, yet it offers an analysis comparable to, and sometimes better than, the methods that use free energy landscapes, thus validating the

  4. When opportunity meets motivation: Neural engagement during social approach is linked to high approach motivation.

    Science.gov (United States)

    Radke, Sina; Seidel, Eva-Maria; Eickhoff, Simon B; Gur, Ruben C; Schneider, Frank; Habel, Ute; Derntl, Birgit

    2016-02-15

    Social rewards are processed by the same dopaminergic-mediated brain networks as non-social rewards, suggesting a common representation of subjective value. Individual differences in personality and motivation influence the reinforcing value of social incentives, but it remains open whether the pursuit of social incentives is analogously supported by the neural reward system when positive social stimuli are connected to approach behavior. To test for a modulation of neural activation by approach motivation, individuals with high and low approach motivation (BAS) completed implicit and explicit social approach-avoidance paradigms during fMRI. High approach motivation was associated with faster implicit approach reactions as well as a trend for higher approach ratings, indicating increased approach tendencies. Implicit and explicit positive social approach was accompanied by stronger recruitment of the nucleus accumbens, middle cingulate cortex, and (pre-)cuneus for individuals with high compared to low approach motivation. These results support and extend prior research on social reward processing, self-other distinctions and affective judgments by linking approach motivation to the engagement of reward-related circuits during motivational reactions to social incentives. This interplay between motivational preferences and motivational contexts might underlie the rewarding experience during social interactions. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Computational Design and Discovery of Ni-Based Alloys and Coatings: Thermodynamic Approaches Validated by Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zi-Kui [Pennsylvania State University; Gleeson, Brian [University of Pittsburgh; Shang, Shunli [Pennsylvania State University; Gheno, Thomas [University of Pittsburgh; Lindwall, Greta [Pennsylvania State University; Zhou, Bi-Cheng [Pennsylvania State University; Liu, Xuan [Pennsylvania State University; Ross, Austin [Pennsylvania State University

    2018-04-23

    This project developed computational tools that can complement and support experimental efforts in order to enable discovery and more efficient development of Ni-base structural materials and coatings. The project goal was reached through an integrated computation-predictive and experimental-validation approach, including first-principles calculations, thermodynamic CALPHAD (CALculation of PHAse Diagram), and experimental investigations on compositions relevant to Ni-base superalloys and coatings in terms of oxide layer growth and microstructure stabilities. The developed description included composition ranges typical for coating alloys and, hence, allow for prediction of thermodynamic properties for these material systems. The calculation of phase compositions, phase fraction, and phase stabilities, which are directly related to properties such as ductility and strength, was a valuable contribution, along with the collection of computational tools that are required to meet the increasing demands for strong, ductile and environmentally-protective coatings. Specifically, a suitable thermodynamic description for the Ni-Al-Cr-Co-Si-Hf-Y system was developed for bulk alloy and coating compositions. Experiments were performed to validate and refine the thermodynamics from the CALPHAD modeling approach. Additionally, alloys produced using predictions from the current computational models were studied in terms of their oxidation performance. Finally, results obtained from experiments aided in the development of a thermodynamic modeling automation tool called ESPEI/pycalphad - for more rapid discovery and development of new materials.

  6. 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.

  7. Novel approaches to develop community-built biological network models for potential drug discovery.

    Science.gov (United States)

    Talikka, Marja; Bukharov, Natalia; Hayes, William S; Hofmann-Apitius, Martin; Alexopoulos, Leonidas; Peitsch, Manuel C; Hoeng, Julia

    2017-08-01

    Hundreds of thousands of data points are now routinely generated in clinical trials by molecular profiling and NGS technologies. A true translation of this data into knowledge is not possible without analysis and interpretation in a well-defined biology context. Currently, there are many public and commercial pathway tools and network models that can facilitate such analysis. At the same time, insights and knowledge that can be gained is highly dependent on the underlying biological content of these resources. Crowdsourcing can be employed to guarantee the accuracy and transparency of the biological content underlining the tools used to interpret rich molecular data. Areas covered: In this review, the authors describe crowdsourcing in drug discovery. The focal point is the efforts that have successfully used the crowdsourcing approach to verify and augment pathway tools and biological network models. Technologies that enable the building of biological networks with the community are also described. Expert opinion: A crowd of experts can be leveraged for the entire development process of biological network models, from ontologies to the evaluation of their mechanistic completeness. The ultimate goal is to facilitate biomarker discovery and personalized medicine by mechanistically explaining patients' differences with respect to disease prevention, diagnosis, and therapy outcome.

  8. High-efficiency combinatorial approach as an effective tool for accelerating metallic biomaterials research and discovery

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, X.D. [School of Material Science and Engineering, Central South University, Changsha, Hunan, 410083 (China); Liu, L.B., E-mail: lbliu.csu@gmail.com [School of Material Science and Engineering, Central South University, Changsha, Hunan, 410083 (China); State Key Laboratory for Powder Metallurgy, Changsha, Hunan, 410083 (China); Zhao, J.-C. [State Key Laboratory for Powder Metallurgy, Changsha, Hunan, 410083 (China); Department of Materials Science and Engineering, The Ohio State University, 2041 College Road, Columbus, OH 43210 (United States); Wang, J.L.; Zheng, F.; Jin, Z.P. [School of Material Science and Engineering, Central South University, Changsha, Hunan, 410083 (China)

    2014-06-01

    A high-efficiency combinatorial approach has been applied to rapidly build the database of composition-dependent elastic modulus and hardness of the Ti–Ta and Ti–Zr–Ta systems. A diffusion multiple of the Ti–Zr–Ta system was manufactured, then annealed at 1173 K for 1800 h, and water quenched to room temperature. Extensive interdiffusion among Ti, Zr and Ta has taken place. Combining nanoindentation and electron probe micro-analysis (EPMA), the elastic modulus, hardness as well as composition across the diffusion multiple were determined. The composition/elastic modulus/hardness relationship of the Ti–Ta and Ti–Zr–Ta alloys has been obtained. It was found that the elastic modulus and hardness depend strongly on the Ta and Zr content. The result can be used to accelerate the discovery/development of bio-titanium alloys for different components in implant prosthesis. - Highlights: • High-efficiency diffusion multiple of Ti–Zr–Ta was manufactured. • Composition-dependent elastic modulus and hardness of the Ti–Ta and Ti–Zr–Ta systems have been obtained effectively, • The methodology and the information can be used to accelerate the discovery/development of bio-titanium alloys.

  9. Facilitating Students' Interaction with Real Gas Properties Using a Discovery-Based Approach and Molecular Dynamics Simulations

    Science.gov (United States)

    Sweet, Chelsea; Akinfenwa, Oyewumi; Foley, Jonathan J., IV

    2018-01-01

    We present an interactive discovery-based approach to studying the properties of real gases using simple, yet realistic, molecular dynamics software. Use of this approach opens up a variety of opportunities for students to interact with the behaviors and underlying theories of real gases. Students can visualize gas behavior under a variety of…

  10. The XML approach to implementing space link extension service management

    Science.gov (United States)

    Tai, W.; Welz, G. A.; Theis, G.; Yamada, T.

    2001-01-01

    A feasibility study has been conducted at JPL, ESOC, and ISAS to assess the possible applications of the eXtensible Mark-up Language (XML) capabilities to the implementation of the CCSDS Space Link Extension (SLE) Service Management function.

  11. Neural networks for link prediction in realistic biomedical graphs: a multi-dimensional evaluation of graph embedding-based approaches.

    Science.gov (United States)

    Crichton, Gamal; Guo, Yufan; Pyysalo, Sampo; Korhonen, Anna

    2018-05-21

    Link prediction in biomedical graphs has several important applications including predicting Drug-Target Interactions (DTI), Protein-Protein Interaction (PPI) prediction and Literature-Based Discovery (LBD). It can be done using a classifier to output the probability of link formation between nodes. Recently several works have used neural networks to create node representations which allow rich inputs to neural classifiers. Preliminary works were done on this and report promising results. However they did not use realistic settings like time-slicing, evaluate performances with comprehensive metrics or explain when or why neural network methods outperform. We investigated how inputs from four node representation algorithms affect performance of a neural link predictor on random- and time-sliced biomedical graphs of real-world sizes (∼ 6 million edges) containing information relevant to DTI, PPI and LBD. We compared the performance of the neural link predictor to those of established baselines and report performance across five metrics. In random- and time-sliced experiments when the neural network methods were able to learn good node representations and there was a negligible amount of disconnected nodes, those approaches outperformed the baselines. In the smallest graph (∼ 15,000 edges) and in larger graphs with approximately 14% disconnected nodes, baselines such as Common Neighbours proved a justifiable choice for link prediction. At low recall levels (∼ 0.3) the approaches were mostly equal, but at higher recall levels across all nodes and average performance at individual nodes, neural network approaches were superior. Analysis showed that neural network methods performed well on links between nodes with no previous common neighbours; potentially the most interesting links. Additionally, while neural network methods benefit from large amounts of data, they require considerable amounts of computational resources to utilise them. Our results indicate

  12. A knowledge discovery approach to urban analysis: Beyoglu Preservation Area as a data mine

    Directory of Open Access Journals (Sweden)

    Ahu Sokmenoglu Sohtorik

    2017-11-01

    Full Text Available Enhancing our knowledge of the complexities of cities in order to empower ourselves to make more informed decisions has always been a challenge for urban research. Recent developments in large-scale computing, together with the new techniques and automated tools for data collection and analysis are opening up promising opportunities for addressing this problem. The main motivation that served as the driving force behind this research is how these developments may contribute to urban data analysis. On this basis, the thesis focuses on urban data analysis in order to search for findings that can enhance our knowledge of urban environments, using the generic process of knowledge discovery using data mining. A knowledge discovery process based on data mining is a fully automated or semi-automated process which involves the application of computational tools and techniques to explore the “previously unknown, and potentially useful information” (Witten & Frank, 2005 hidden in large and often complex and multi-dimensional databases. This information can be obtained in the form of correlations amongst variables, data groupings (classes and clusters or more complex hypotheses (probabilistic rules of co-occurrence, performance vectors of prediction models etc.. This research targets researchers and practitioners working in the field of urban studies who are interested in quantitative/ computational approaches to urban data analysis and specifically aims to engage the interest of architects, urban designers and planners who do not have a background in statistics or in using data mining methods in their work. Accordingly, the overall aim of the thesis is the development of a knowledge discovery approach to urban analysis; a domain-specific adaptation of the generic process of knowledge discovery using data mining enabling the analyst to discover ‘relational urban knowledge’. ‘Relational urban knowledge’ is a term employed in this thesis to refer

  13. An Ontology-supported Approach for Automatic Chaining of Web Services in Geospatial Knowledge Discovery

    Science.gov (United States)

    di, L.; Yue, P.; Yang, W.; Yu, G.

    2006-12-01

    Recent developments in geospatial semantic Web have shown promise for automatic discovery, access, and use of geospatial Web services to quickly and efficiently solve particular application problems. With the semantic Web technology, it is highly feasible to construct intelligent geospatial knowledge systems that can provide answers to many geospatial application questions. A key challenge in constructing such intelligent knowledge system is to automate the creation of a chain or process workflow that involves multiple services and highly diversified data and can generate the answer to a specific question of users. This presentation discusses an approach for automating composition of geospatial Web service chains by employing geospatial semantics described by geospatial ontologies. It shows how ontology-based geospatial semantics are used for enabling the automatic discovery, mediation, and chaining of geospatial Web services. OWL-S is used to represent the geospatial semantics of individual Web services and the type of the services it belongs to and the type of the data it can handle. The hierarchy and classification of service types are described in the service ontology. The hierarchy and classification of data types are presented in the data ontology. For answering users' geospatial questions, an Artificial Intelligent (AI) planning algorithm is used to construct the service chain by using the service and data logics expressed in the ontologies. The chain can be expressed as a graph with nodes representing services and connection weights representing degrees of semantic matching between nodes. The graph is a visual representation of logical geo-processing path for answering users' questions. The graph can be instantiated to a physical service workflow for execution to generate the answer to a user's question. A prototype system, which includes real world geospatial applications, is implemented to demonstrate the concept and approach.

  14. A Fine-Grained API Link Prediction Approach Supporting CMDA Mashup Recommendation

    Science.gov (United States)

    Zhang, J.; Bao, Q.; Lee, T. J.; Ramachandran, R.; Lee, S.; Pan, L.; Gatlin, P. N.; Maskey, M.

    2017-12-01

    Service (API) discovery and recommendation is key to the wide spread of service oriented architecture and service oriented software engineering. Service recommendation typically relies on service linkage prediction calculated by the semantic distances (or similarities) among services based on their collection of inherent attributes. Given a specific context (mashup goal), however, different attributes may contribute differently to a service linkage. In this work, instead of training a model for all attributes as a whole, a novel approach is presented to simultaneously train separate models for individual attributes. Our contributions are summarized in three-fold. First is that we have developed a scalable attribute-level data model, featuring scalability and extensibility. We have extended Multiplicative Attribute Graph (MAG) model to represent node profiles featuring rich categorical attributes, while relaxing its constraint of requiring a priori knowledge of predefined attributes. LDA is leveraged to dynamically identify attributes based on attribute modeling, and multiple Gaussian fit is applied to find global optimal values. The second contribution is that we have seamlessly integrated the latent relationships between API attributes as well as observed network structure based on historical API usage data. Such a layered information model enables us to predict the probability of a link between two APIs based on their attribute link affinities carrying a variety of information including meta data, semantic data, historical usage data, as well as crowdsourcing user comments and annotations. The third contribution is that we have developed a finegrained context-aware mashup-API recommendation technique. On top of individual models trained for separate attributes, a dedicated layer is trained to represent the latent attribute distribution regarding mashup purpose, i.e., sensitivity of attributes to context. Thus, given the description of an intended mashup, the

  15. Contextual Approach with Guided Discovery Learning and Brain Based Learning in Geometry Learning

    Science.gov (United States)

    Kartikaningtyas, V.; Kusmayadi, T. A.; Riyadi

    2017-09-01

    The aim of this study was to combine the contextual approach with Guided Discovery Learning (GDL) and Brain Based Learning (BBL) in geometry learning of junior high school. Furthermore, this study analysed the effect of contextual approach with GDL and BBL in geometry learning. GDL-contextual and BBL-contextual was built from the steps of GDL and BBL that combined with the principles of contextual approach. To validate the models, it uses quasi experiment which used two experiment groups. The sample had been chosen by stratified cluster random sampling. The sample was 150 students of grade 8th in junior high school. The data were collected through the student’s mathematics achievement test that given after the treatment of each group. The data analysed by using one way ANOVA with different cell. The result shows that GDL-contextual has not different effect than BBL-contextual on mathematics achievement in geometry learning. It means both the two models could be used in mathematics learning as the innovative way in geometry learning.

  16. Integrating Genomic Data Sets for Knowledge Discovery: An Informed Approach to Management of Captive Endangered Species

    Directory of Open Access Journals (Sweden)

    Kristopher J. L. Irizarry

    2016-01-01

    Full Text Available Many endangered captive populations exhibit reduced genetic diversity resulting in health issues that impact reproductive fitness and quality of life. Numerous cost effective genomic sequencing and genotyping technologies provide unparalleled opportunity for incorporating genomics knowledge in management of endangered species. Genomic data, such as sequence data, transcriptome data, and genotyping data, provide critical information about a captive population that, when leveraged correctly, can be utilized to maximize population genetic variation while simultaneously reducing unintended introduction or propagation of undesirable phenotypes. Current approaches aimed at managing endangered captive populations utilize species survival plans (SSPs that rely upon mean kinship estimates to maximize genetic diversity while simultaneously avoiding artificial selection in the breeding program. However, as genomic resources increase for each endangered species, the potential knowledge available for management also increases. Unlike model organisms in which considerable scientific resources are used to experimentally validate genotype-phenotype relationships, endangered species typically lack the necessary sample sizes and economic resources required for such studies. Even so, in the absence of experimentally verified genetic discoveries, genomics data still provides value. In fact, bioinformatics and comparative genomics approaches offer mechanisms for translating these raw genomics data sets into integrated knowledge that enable an informed approach to endangered species management.

  17. Integrating Genomic Data Sets for Knowledge Discovery: An Informed Approach to Management of Captive Endangered Species.

    Science.gov (United States)

    Irizarry, Kristopher J L; Bryant, Doug; Kalish, Jordan; Eng, Curtis; Schmidt, Peggy L; Barrett, Gini; Barr, Margaret C

    2016-01-01

    Many endangered captive populations exhibit reduced genetic diversity resulting in health issues that impact reproductive fitness and quality of life. Numerous cost effective genomic sequencing and genotyping technologies provide unparalleled opportunity for incorporating genomics knowledge in management of endangered species. Genomic data, such as sequence data, transcriptome data, and genotyping data, provide critical information about a captive population that, when leveraged correctly, can be utilized to maximize population genetic variation while simultaneously reducing unintended introduction or propagation of undesirable phenotypes. Current approaches aimed at managing endangered captive populations utilize species survival plans (SSPs) that rely upon mean kinship estimates to maximize genetic diversity while simultaneously avoiding artificial selection in the breeding program. However, as genomic resources increase for each endangered species, the potential knowledge available for management also increases. Unlike model organisms in which considerable scientific resources are used to experimentally validate genotype-phenotype relationships, endangered species typically lack the necessary sample sizes and economic resources required for such studies. Even so, in the absence of experimentally verified genetic discoveries, genomics data still provides value. In fact, bioinformatics and comparative genomics approaches offer mechanisms for translating these raw genomics data sets into integrated knowledge that enable an informed approach to endangered species management.

  18. A Bioinorganic Approach to Fragment-Based Drug Discovery Targeting Metalloenzymes.

    Science.gov (United States)

    Cohen, Seth M

    2017-08-15

    Metal-dependent enzymes (i.e., metalloenzymes) make up a large fraction of all enzymes and are critically important in a wide range of biological processes, including DNA modification, protein homeostasis, antibiotic resistance, and many others. Consequently, metalloenzymes represent a vast and largely untapped space for drug development. The discovery of effective therapeutics that target metalloenzymes lies squarely at the interface of bioinorganic and medicinal chemistry and requires expertise, methods, and strategies from both fields to mount an effective campaign. In this Account, our research program that brings together the principles and methods of bioinorganic and medicinal chemistry are described, in an effort to bridge the gap between these fields and address an important class of medicinal targets. Fragment-based drug discovery (FBDD) is an important drug discovery approach that is particularly well suited for metalloenzyme inhibitor development. FBDD uses relatively small but diverse chemical structures that allow for the assembly of privileged molecular collections that focus on a specific feature of the target enzyme. For metalloenzyme inhibition, the specific feature is rather obvious, namely, a metal-dependent active site. Surprisingly, prior to our work, the exploration of diverse molecular fragments for binding the metal active sites of metalloenzymes was largely unexplored. By assembling a modest library of metal-binding pharmacophores (MBPs), we have been able to find lead hits for many metalloenzymes and, from these hits, develop inhibitors that act via novel mechanisms of action. A specific case study on the use of this strategy to identify a first-in-class inhibitor of zinc-dependent Rpn11 (a component of the proteasome) is highlighted. The application of FBDD for the development of metalloenzyme inhibitors has raised several other compelling questions, such as how the metalloenzyme active site influences the coordination chemistry of bound

  19. Therapeutic approaches to genetic ion channelopathies and perspectives in drug discovery

    Directory of Open Access Journals (Sweden)

    Paola eImbrici

    2016-05-01

    Full Text Available In the human genome more than 400 genes encode ion channels, which are transmembrane proteins mediating ion fluxes across membranes. Being expressed in all cell types, they are involved in almost all physiological processes, including sense perception, neurotransmission, muscle contraction, secretion, immune response, cell proliferation and differentiation. Due to the widespread tissue distribution of ion channels and their physiological functions, mutations in genes encoding ion channel subunits, or their interacting proteins, are responsible for inherited ion channelopathies. These diseases can range from common to very rare disorders and their severity can be mild, disabling, or life-threatening. In spite of this, ion channels are the primary target of only about 5% of the marketed drugs suggesting their potential in drug discovery. The current review summarizes the therapeutic management of the principal ion channelopathies of central and peripheral nervous system, heart, kidney, bone, skeletal muscle and pancreas, resulting from mutations in calcium, sodium, potassium and chloride ion channels. For most channelopathies the therapy is mainly empirical and symptomatic, often limited by lack of efficacy and tolerability for a significant number of patients. Other channelopathies can exploit ion channel targeted drugs, such as marketed sodium channel blockers. Developing new and more specific therapeutic approaches is therefore required. To this aim, a major advancement in the pharmacotherapy of channelopathies has been the discovery that ion channel mutations lead to change in biophysics that can in turn specifically modify the sensitivity to drugs: this opens the way to a pharmacogenetics strategy, allowing the development of a personalized therapy with increased efficacy and reduced side effects. In addition, the identification of disease modifiers in ion channelopathies appears an alternative strategy to discover novel druggable targets.

  20. Discovery and annotation of small proteins using genomics, proteomics and computational approaches

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaohan; Tschaplinski, Timothy J.; Hurst, Gregory B.; Jawdy, Sara; Abraham, Paul E.; Lankford, Patricia K.; Adams, Rachel M.; Shah, Manesh B.; Hettich, Robert L.; Lindquist, Erika; Kalluri, Udaya C.; Gunter, Lee E.; Pennacchio, Christa; Tuskan, Gerald A.

    2011-03-02

    Small proteins (10 200 amino acids aa in length) encoded by short open reading frames (sORF) play important regulatory roles in various biological processes, including tumor progression, stress response, flowering, and hormone signaling. However, ab initio discovery of small proteins has been relatively overlooked. Recent advances in deep transcriptome sequencing make it possible to efficiently identify sORFs at the genome level. In this study, we obtained 2.6 million expressed sequence tag (EST) reads from Populus deltoides leaf transcriptome and reconstructed full-length transcripts from the EST sequences. We identified an initial set of 12,852 sORFs encoding proteins of 10 200 aa in length. Three computational approaches were then used to enrich for bona fide protein-coding sORFs from the initial sORF set: (1) codingpotential prediction, (2) evolutionary conservation between P. deltoides and other plant species, and (3) gene family clustering within P. deltoides. As a result, a high-confidence sORF candidate set containing 1469 genes was obtained. Analysis of the protein domains, non-protein-coding RNA motifs, sequence length distribution, and protein mass spectrometry data supported this high-confidence sORF set. In the high-confidence sORF candidate set, known protein domains were identified in 1282 genes (higher-confidence sORF candidate set), out of which 611 genes, designated as highest-confidence candidate sORF set, were supported by proteomics data. Of the 611 highest-confidence candidate sORF genes, 56 were new to the current Populus genome annotation. This study not only demonstrates that there are potential sORF candidates to be annotated in sequenced genomes, but also presents an efficient strategy for discovery of sORFs in species with no genome annotation yet available.

  1. Constructivist Practicies Through Guided Discovery Approach: The Effect on Students' Cognitive Achievements in Nigerian Senior Secondary School Physics

    Directory of Open Access Journals (Sweden)

    A.O. Akinbobola

    2009-12-01

    Full Text Available The study investigated constructivist practices through guided discovery approach and the effect on students’ cognitive achievement in Nigerian senior secondary school Physics. The study adopted pretest-posttest control group design. A criterion sampling technique was used to select six schools out of nine schools that met the criteria. A total of 278 students took part in the study; this was made up of 141 male students and 137 female students in their respective intact classes. Physic Achievement Test (PAT with the internal consistency of 0.77 using Kuder-Richardson formula (21 was the instrument used in collecting data. The data were analyzed using Analysis of Covariance (ANCOVA and t-test. The results showed that guided discovery approaches was the most effective in facilitating students’ achievement in physics after being taught using a pictorial organizer. This was followed by demonstration while expository was found to be the least effective. Also, there exists no significant difference in the achievement of male and female physics students taught with guided discovery, demonstration and expository teaching approaches and corresponding exposure to a pictorial organizer. It is recommended that physics teachers should endeavor to use constructivist practices through guided discovery approach in order to engage students in problem solving activities, independent learning, critical thinking and understanding, and creative learning, rather than in rote learning and memorization.

  2. The Genetics of Obsessive-Compulsive Disorder and Tourette Syndrome: An Epidemiological and Pathway-Based Approach for Gene Discovery

    Science.gov (United States)

    Grados, Marco A.

    2010-01-01

    Objective: To provide a contemporary perspective on genetic discovery methods applied to obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). Method: A review of research trends in genetics research in OCD and TS is conducted, with emphasis on novel approaches. Results: Genome-wide association studies (GWAS) are now in progress in OCD…

  3. The Effect of Concept Mapping-Guided Discovery Integrated Teaching Approach on Chemistry Students' Achievement and Retention

    Science.gov (United States)

    Fatokun, K. V. F.; Eniayeju, P. A.

    2014-01-01

    This study investigates the effects of Concept Mapping-Guided Discovery Integrated Teaching Approach on the achievement and retention of chemistry students. The sample comprised 162 Senior Secondary two (SS 2) students drawn from two Science Schools in Nasarawa State, Central Nigeria with equivalent mean scores of 9.68 and 9.49 in their pre-test.…

  4. Educability as a Link of Contemporary Civil Experience: Research Approaches

    Directory of Open Access Journals (Sweden)

    Julio Groppa Aquino

    2016-05-01

    Full Text Available This text argues that the educability of citizens is objectified in terms of a demand for diffuse and perpetual training, which has become a foundational link of social existence. This statement is based upon the results of twelve researches carried out by a group from the school of Education of the University of São Paulo, devoted to Foucaultian studies in education. It is an effort to analyze the relationship between contemporary governmentality and certain ongoing educational imperatives from different social fields.

  5. A semantically rich and standardised approach enhancing discovery of sensor data and metadata

    Science.gov (United States)

    Kokkinaki, Alexandra; Buck, Justin; Darroch, Louise

    2016-04-01

    The marine environment plays an essential role in the earth's climate. To enhance the ability to monitor the health of this important system, innovative sensors are being produced and combined with state of the art sensor technology. As the number of sensors deployed is continually increasing,, it is a challenge for data users to find the data that meet their specific needs. Furthermore, users need to integrate diverse ocean datasets originating from the same or even different systems. Standards provide a solution to the above mentioned challenges. The Open Geospatial Consortium (OGC) has created Sensor Web Enablement (SWE) standards that enable different sensor networks to establish syntactic interoperability. When combined with widely accepted controlled vocabularies, they become semantically rich and semantic interoperability is achievable. In addition, Linked Data is the recommended best practice for exposing, sharing and connecting information on the Semantic Web using Uniform Resource Identifiers (URIs), Resource Description Framework (RDF) and RDF Query Language (SPARQL). As part of the EU-funded SenseOCEAN project, the British Oceanographic Data Centre (BODC) is working on the standardisation of sensor metadata enabling 'plug and play' sensor integration. Our approach combines standards, controlled vocabularies and persistent URIs to publish sensor descriptions, their data and associated metadata as 5 star Linked Data and OGC SWE (SensorML, Observations & Measurements) standard. Thus sensors become readily discoverable, accessible and useable via the web. Content and context based searching is also enabled since sensors descriptions are understood by machines. Additionally, sensor data can be combined with other sensor or Linked Data datasets to form knowledge. This presentation will describe the work done in BODC to achieve syntactic and semantic interoperability in the sensor domain. It will illustrate the reuse and extension of the Semantic Sensor

  6. Towards a routine application of Top-Down approaches for label-free discovery workflows.

    Science.gov (United States)

    Schmit, Pierre-Olivier; Vialaret, Jerome; Wessels, Hans J C T; van Gool, Alain J; Lehmann, Sylvain; Gabelle, Audrey; Wood, Jason; Bern, Marshall; Paape, Rainer; Suckau, Detlev; Kruppa, Gary; Hirtz, Christophe

    2018-03-20

    Thanks to proteomics investigations, our vision of the role of different protein isoforms in the pathophysiology of diseases has largely evolved. The idea that protein biomarkers like tau, amyloid peptides, ApoE, cystatin, or neurogranin are represented in body fluids as single species is obviously over-simplified, as most proteins are present in different isoforms and subjected to numerous processing and post-translational modifications. Measuring the intact mass of proteins by MS has the advantage to provide information on the presence and relative amount of the different proteoforms. Such Top-Down approaches typically require a high degree of sample pre-fractionation to allow the MS system to deliver optimal performance in terms of dynamic range, mass accuracy and resolution. In clinical studies, however, the requirements for pre-analytical robustness and sample size large enough for statistical power restrict the routine use of a high degree of sample pre-fractionation. In this study, we have investigated the capacities of current-generation Ultra-High Resolution Q-Tof systems to deal with high complexity intact protein samples and have evaluated the approach on a cohort of patients suffering from neurodegenerative disease. Statistical analysis has shown that several proteoforms can be used to distinguish Alzheimer disease patients from patients suffering from other neurodegenerative disease. Top-down approaches have an extremely high biological relevance, especially when it comes to biomarker discovery, but the necessary pre-fractionation constraints are not easily compatible with the robustness requirements and the size of clinical sample cohorts. We have demonstrated that intact protein profiling studies could be run on UHR-Q-ToF with limited pre-fractionation. The proteoforms that have been identified as candidate biomarkers in the-proof-of concept study are derived from proteins known to play a role in the pathophysiology process of Alzheimer disease

  7. a Task-Driven Disaster Data Link Approach

    Science.gov (United States)

    Qiu, L. Y.; Zhu, Q.; Gu, J. Y.; Du, Z. Q.

    2015-08-01

    With the rapid development of sensor networks and Earth observation technology, a large quantity of disaster-related data is available, such as remotely sensed data, historic data, cases data, simulation data, disaster products and so on. However, the efficiency of current data management and service systems has become increasingly serious due to the task variety and heterogeneous data. For emergency task-oriented applications, data searching mainly relies on artificial experience based on simple metadata index, whose high time-consuming and low accuracy cannot satisfy the requirements of disaster products on velocity and veracity. In this paper, a task-oriented linking method is proposed for efficient disaster data management and intelligent service, with the objectives of 1) putting forward ontologies of disaster task and data to unify the different semantics of multi-source information, 2) identifying the semantic mapping from emergency tasks to multiple sources on the basis of uniform description in 1), 3) linking task-related data automatically and calculating the degree of correlation between each data and a target task. The method breaks through traditional static management of disaster data and establishes a base for intelligent retrieval and active push of disaster information. The case study presented in this paper illustrates the use of the method with a flood emergency relief task.

  8. A wavelet-based approach to the discovery of themes and sections in monophonic melodies

    DEFF Research Database (Denmark)

    Velarde, Gissel; Meredith, David

    We present the computational method submitted to the MIREX 2014 Discovery of Repeated Themes & Sections task, and the results on the monophonic version of the JKU Patterns Development Database. In the context of pattern discovery in monophonic music, the idea behind our method is that, with a good...

  9. Capacity-Approaching Superposition Coding for Optical Fiber Links

    DEFF Research Database (Denmark)

    Estaran Tolosa, Jose Manuel; Zibar, Darko; Tafur Monroy, Idelfonso

    2014-01-01

    We report on the first experimental demonstration of superposition coded modulation (SCM) for polarization-multiplexed coherent-detection optical fiber links. The proposed coded modulation scheme is combined with phase-shifted bit-to-symbol mapping (PSM) in order to achieve geometric and passive......-SCM) is employed in the framework of bit-interleaved coded modulation with iterative decoding (BICM-ID) for forward error correction. The fiber transmission system is characterized in terms of signal-to-noise ratio for back-to-back case and correlated with simulated results for ideal transmission over additive...... white Gaussian noise channel. Thereafter, successful demodulation and decoding after dispersion-unmanaged transmission over 240-km standard single mode fiber of dual-polarization 6-Gbaud 16-, 32- and 64-ary SCM-PSM is experimentally demonstrated....

  10. A Hybrid Information Mining Approach for Knowledge Discovery in Cardiovascular Disease (CVD

    Directory of Open Access Journals (Sweden)

    Stefania Pasanisi

    2018-04-01

    Full Text Available The healthcare ambit is usually perceived as “information rich” yet “knowledge poor”. Nowadays, an unprecedented effort is underway to increase the use of business intelligence techniques to solve this problem. Heart disease (HD is a major cause of mortality in modern society. This paper analyzes the risk factors that have been identified in cardiovascular disease (CVD surveillance systems. The Heart Care study identifies attributes related to CVD risk (gender, age, smoking habit, etc. and other dependent variables that include a specific form of CVD (diabetes, hypertension, cardiac disease, etc.. In this paper, we combine Clustering, Association Rules, and Neural Networks for the assessment of heart-event-related risk factors, targeting the reduction of CVD risk. With the use of the K-means algorithm, significant groups of patients are found. Then, the Apriori algorithm is applied in order to understand the kinds of relations between the attributes within the dataset, first looking within the whole dataset and then refining the results through the subsets defined by the clusters. Finally, both results allow us to better define patients’ characteristics in order to make predictions about CVD risk with a Multilayer Perceptron Neural Network. The results obtained with the hybrid information mining approach indicate that it is an effective strategy for knowledge discovery concerning chronic diseases, particularly for CVD risk.

  11. Mining the Proteome of subsp. ATCC 25586 for Potential Therapeutics Discovery: An Approach

    Directory of Open Access Journals (Sweden)

    Abdul Musaweer Habib

    2016-12-01

    Full Text Available The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1,499 proteins of F. nucleatum, which have no homolog's in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the Kyoto Encyclopedia of Genes and Genomes (KEGG Automated Annotation Server (KAAS resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the three dimensional structure of these three proteins. Finally, determination of ligand binding sites of the 2 key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against F. nucleatum.

  12. Pharmacokinetics in Drug Discovery: An Exposure-Centred Approach to Optimising and Predicting Drug Efficacy and Safety.

    Science.gov (United States)

    Reichel, Andreas; Lienau, Philip

    2016-01-01

    The role of pharmacokinetics (PK) in drug discovery is to support the optimisation of the absorption, distribution, metabolism and excretion (ADME) properties of lead compounds with the ultimate goal to attain a clinical candidate which achieves a concentration-time profile in the body that is adequate for the desired efficacy and safety profile. A thorough characterisation of the lead compounds aiming at the identification of the inherent PK liabilities also includes an early generation of PK/PD relationships linking in vitro potency and target exposure/engagement with expression of pharmacological activity (mode-of-action) and efficacy in animal studies. The chapter describes an exposure-centred approach to lead generation, lead optimisation and candidate selection and profiling that focuses on a stepwise generation of an understanding between PK/exposure and PD/efficacy relationships by capturing target exposure or surrogates thereof and cellular mode-of-action readouts in vivo. Once robust PK/PD relationship in animal PD models has been constructed, it is translated to anticipate the pharmacologically active plasma concentrations in patients and the human therapeutic dose and dosing schedule which is also based on the prediction of the PK behaviour in human as described herein. The chapter outlines how the level of confidence in the predictions increases with the level of understanding of both the PK and the PK/PD of the new chemical entities (NCE) in relation to the disease hypothesis and the ability to propose safe and efficacious doses and dosing schedules in responsive patient populations. A sound identification of potential drug metabolism and pharmacokinetics (DMPK)-related development risks allows proposing of an effective de-risking strategy for the progression of the project that is able to reduce uncertainties and to increase the probability of success during preclinical and clinical development.

  13. Novel approach of fragment-based lead discovery applied to renin inhibitors.

    Science.gov (United States)

    Tawada, Michiko; Suzuki, Shinkichi; Imaeda, Yasuhiro; Oki, Hideyuki; Snell, Gyorgy; Behnke, Craig A; Kondo, Mitsuyo; Tarui, Naoki; Tanaka, Toshimasa; Kuroita, Takanobu; Tomimoto, Masaki

    2016-11-15

    A novel approach was conducted for fragment-based lead discovery and applied to renin inhibitors. The biochemical screening of a fragment library against renin provided the hit fragment which showed a characteristic interaction pattern with the target protein. The hit fragment bound only to the S1, S3, and S3 SP (S3 subpocket) sites without any interactions with the catalytic aspartate residues (Asp32 and Asp215 (pepsin numbering)). Prior to making chemical modifications to the hit fragment, we first identified its essential binding sites by utilizing the hit fragment's substructures. Second, we created a new and smaller scaffold, which better occupied the identified essential S3 and S3 SP sites, by utilizing library synthesis with high-throughput chemistry. We then revisited the S1 site and efficiently explored a good building block attaching to the scaffold with library synthesis. In the library syntheses, the binding modes of each pivotal compound were determined and confirmed by X-ray crystallography and the library was strategically designed by structure-based computational approach not only to obtain a more active compound but also to obtain informative Structure Activity Relationship (SAR). As a result, we obtained a lead compound offering synthetic accessibility as well as the improved in vitro ADMET profiles. The fragments and compounds possessing a characteristic interaction pattern provided new structural insights into renin's active site and the potential to create a new generation of renin inhibitors. In addition, we demonstrated our FBDD strategy integrating highly sensitive biochemical assay, X-ray crystallography, and high-throughput synthesis and in silico library design aimed at fragment morphing at the initial stage was effective to elucidate a pocket profile and a promising lead compound. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. DISCOVERY LEARNING APPROACH IN IMPROVING ARABIC ABILITY OF PRE-SERVICE TEACHERS IN RELIGIOUS TRAINING CENTRE OF MAKASSAR

    Directory of Open Access Journals (Sweden)

    Masrariah Amin

    2017-04-01

    Full Text Available Discovery Learning can be defined as the learning that takes place when the student is not presented with subject matter in the final form, rather he/she is required to find out the concepts by him/her self. This research aims to describe and analyze discovery learning method to strategically improve the comprehension and reasoning ability of Arabic pre-service teachers, which can motivate and enhance their creativity in order to enrich their insight about Arabic teaching as well, especially those who are in training centre. This research was undertaken in two classes of Makassar Religious Training Centre during June-August 2016. The design of this research is experiment with discovery learning approach with randomized pretest-posttest control group design. It was done randomly when to choosing the participants to be experiment and control group. Based on hypothesis testing, discovery learning has positive effects on the pre-service teachers’ Arabic ability in training centre to understand and analyze Arabic. Therefore, based on two-variance analysis; control and experiment group, there is difference on teachers’ comprehension and reasoning ability in learning Arabic between experiment and control group by using discovery learning and conventional method.

  15. Discovery of Intermetallic Compounds from Traditional to Machine-Learning Approaches.

    Science.gov (United States)

    Oliynyk, Anton O; Mar, Arthur

    2018-01-16

    Intermetallic compounds are bestowed by diverse compositions, complex structures, and useful properties for many materials applications. How metallic elements react to form these compounds and what structures they adopt remain challenging questions that defy predictability. Traditional approaches offer some rational strategies to prepare specific classes of intermetallics, such as targeting members within a modular homologous series, manipulating building blocks to assemble new structures, and filling interstitial sites to create stuffed variants. Because these strategies rely on precedent, they cannot foresee surprising results, by definition. Exploratory synthesis, whether through systematic phase diagram investigations or serendipity, is still essential for expanding our knowledge base. Eventually, the relationships may become too complex for the pattern recognition skills to be reliably or practically performed by humans. Complementing these traditional approaches, new machine-learning approaches may be a viable alternative for materials discovery, not only among intermetallics but also more generally to other chemical compounds. In this Account, we survey our own efforts to discover new intermetallic compounds, encompassing gallides, germanides, phosphides, arsenides, and others. We apply various machine-learning methods (such as support vector machine and random forest algorithms) to confront two significant questions in solid state chemistry. First, what crystal structures are adopted by a compound given an arbitrary composition? Initial efforts have focused on binary equiatomic phases AB, ternary equiatomic phases ABC, and full Heusler phases AB 2 C. Our analysis emphasizes the use of real experimental data and places special value on confirming predictions through experiment. Chemical descriptors are carefully chosen through a rigorous procedure called cluster resolution feature selection. Predictions for crystal structures are quantified by evaluating

  16. 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.

  17. 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.

  18. 3D profile-based approach to proteome-wide discovery of novel human chemokines.

    Directory of Open Access Journals (Sweden)

    Aurelie Tomczak

    Full Text Available Chemokines are small secreted proteins with important roles in immune responses. They consist of a conserved three-dimensional (3D structure, so-called IL8-like chemokine fold, which is supported by disulfide bridges characteristic of this protein family. Sequence- and profile-based computational methods have been proficient in discovering novel chemokines by making use of their sequence-conserved cysteine patterns. However, it has been recently shown that some chemokines escaped annotation by these methods due to low sequence similarity to known chemokines and to different arrangement of cysteines in sequence and in 3D. Innovative methods overcoming the limitations of current techniques may allow the discovery of new remote homologs in the still functionally uncharacterized fraction of the human genome. We report a novel computational approach for proteome-wide identification of remote homologs of the chemokine family that uses fold recognition techniques in combination with a scaffold-based automatic mapping of disulfide bonds to define a 3D profile of the chemokine protein family. By applying our methodology to all currently uncharacterized human protein sequences, we have discovered two novel proteins that, without having significant sequence similarity to known chemokines or characteristic cysteine patterns, show strong structural resemblance to known anti-HIV chemokines. Detailed computational analysis and experimental structural investigations based on mass spectrometry and circular dichroism support our structural predictions and highlight several other chemokine-like features. The results obtained support their functional annotation as putative novel chemokines and encourage further experimental characterization. The identification of remote homologs of human chemokines may provide new insights into the molecular mechanisms causing pathologies such as cancer or AIDS, and may contribute to the development of novel treatments. Besides

  19. 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.

  20. Computational approaches for discovery of common immunomodulators in fungal infections: towards broad-spectrum immunotherapeutic interventions.

    Science.gov (United States)

    Kidane, Yared H; Lawrence, Christopher; Murali, T M

    2013-10-07

    Fungi are the second most abundant type of human pathogens. Invasive fungal pathogens are leading causes of life-threatening infections in clinical settings. Toxicity to the host and drug-resistance are two major deleterious issues associated with existing antifungal agents. Increasing a host's tolerance and/or immunity to fungal pathogens has potential to alleviate these problems. A host's tolerance may be improved by modulating the immune system such that it responds more rapidly and robustly in all facets, ranging from the recognition of pathogens to their clearance from the host. An understanding of biological processes and genes that are perturbed during attempted fungal exposure, colonization, and/or invasion will help guide the identification of endogenous immunomodulators and/or small molecules that activate host-immune responses such as specialized adjuvants. In this study, we present computational techniques and approaches using publicly available transcriptional data sets, to predict immunomodulators that may act against multiple fungal pathogens. Our study analyzed data sets derived from host cells exposed to five fungal pathogens, namely, Alternaria alternata, Aspergillus fumigatus, Candida albicans, Pneumocystis jirovecii, and Stachybotrys chartarum. We observed statistically significant associations between host responses to A. fumigatus and C. albicans. Our analysis identified biological processes that were consistently perturbed by these two pathogens. These processes contained both immune response-inducing genes such as MALT1, SERPINE1, ICAM1, and IL8, and immune response-repressing genes such as DUSP8, DUSP6, and SPRED2. We hypothesize that these genes belong to a pool of common immunomodulators that can potentially be activated or suppressed (agonized or antagonized) in order to render the host more tolerant to infections caused by A. fumigatus and C. albicans. Our computational approaches and methodologies described here can now be applied to

  1. The Implementation of Discovery Learning Model with Scientific Learning Approach to Improve Students’ Critical Thinking in Learning History

    Directory of Open Access Journals (Sweden)

    Edi Nurcahyo

    2018-03-01

    Full Text Available Historical learning has not reached optimal in the learning process. It is caused by the history teachers’ learning model has not used the innovative learning models. Furthermore, it supported by the perception of students to the history subject because it does not become final exam (UN subject so it makes less improvement and builds less critical thinking in students’ daily learning. This is due to the lack of awareness of historical events and the availability of history books for students and teachers in the library are still lacking. Discovery learning with scientific approach encourages students to solve problems actively and able to improve students' critical thinking skills with scientific approach so student can build scientific thinking include observing, asking, reasoning, trying, and networking   Keywords: discovery learning, scientific, critical thinking

  2. RHSEG and Subdue: Background and Preliminary Approach for Combining these Technologies for Enhanced Image Data Analysis, Mining and Knowledge Discovery

    Science.gov (United States)

    Tilton, James C.; Cook, Diane J.

    2008-01-01

    Under a project recently selected for funding by NASA's Science Mission Directorate under the Applied Information Systems Research (AISR) program, Tilton and Cook will design and implement the integration of the Subdue graph based knowledge discovery system, developed at the University of Texas Arlington and Washington State University, with image segmentation hierarchies produced by the RHSEG software, developed at NASA GSFC, and perform pilot demonstration studies of data analysis, mining and knowledge discovery on NASA data. Subdue represents a method for discovering substructures in structural databases. Subdue is devised for general-purpose automated discovery, concept learning, and hierarchical clustering, with or without domain knowledge. Subdue was developed by Cook and her colleague, Lawrence B. Holder. For Subdue to be effective in finding patterns in imagery data, the data must be abstracted up from the pixel domain. An appropriate abstraction of imagery data is a segmentation hierarchy: a set of several segmentations of the same image at different levels of detail in which the segmentations at coarser levels of detail can be produced from simple merges of regions at finer levels of detail. The RHSEG program, a recursive approximation to a Hierarchical Segmentation approach (HSEG), can produce segmentation hierarchies quickly and effectively for a wide variety of images. RHSEG and HSEG were developed at NASA GSFC by Tilton. In this presentation we provide background on the RHSEG and Subdue technologies and present a preliminary analysis on how RHSEG and Subdue may be combined to enhance image data analysis, mining and knowledge discovery.

  3. A Curriculum-Linked Professional Development Approach to Support Teachers' Adoption of Web GIS Tectonics Investigations

    Science.gov (United States)

    Bodzin, Alec; Anastasio, David; Sahagian, Dork; Henry, Jill Burrows

    2016-01-01

    A curriculum-linked professional development approach designed to support middle level science teachers' understandings about tectonics and geospatial pedagogical content knowledge was developed. This approach takes into account limited face-to-face professional development time and instead provides pedagogical support within the design of a…

  4. Exploring Alternative Characteristic Curve Approaches to Linking Parameter Estimates from the Generalized Partial Credit Model.

    Science.gov (United States)

    Roberts, James S.; Bao, Han; Huang, Chun-Wei; Gagne, Phill

    Characteristic curve approaches for linking parameters from the generalized partial credit model were examined for cases in which common (anchor) items are calibrated separately in two groups. Three of these approaches are simple extensions of the test characteristic curve (TCC), item characteristic curve (ICC), and operating characteristic curve…

  5. AM: An Artificial Intelligence Approach to Discovery in Mathematics as Heuristic Search

    Science.gov (United States)

    1976-07-01

    deficiency . The idea of "Intuitions" facets was a flop. Intuitions were meant to model reality, at least little pieces of it, so that AM could...Discovery in Mathematic, as Heuristic Search -323- s Tk2 ** Check examples of Single-ADD, because many examples have recently been found, but not yet

  6. Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders.

    Science.gov (United States)

    Han, Chanshuai; Chaineau, Mathilde; Chen, Carol X-Q; Beitel, Lenore K; Durcan, Thomas M

    2018-01-01

    Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs) from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop "first-of-their-kind" disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI) and its partners are piloting an "Open Science" model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders.

  7. Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Chanshuai Han

    2018-02-01

    Full Text Available Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop “first-of-their-kind” disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI and its partners are piloting an “Open Science” model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders.

  8. Searching for the Prosocial Personality: A Big Five Approach to Linking Personality and Prosocial Behavior.

    Science.gov (United States)

    Habashi, Meara M; Graziano, William G; Hoover, Ann E

    2016-09-01

    The search for the prosocial personality has been long and controversial. The current research explores the general patterns underlying prosocial decisions, linking personality, emotion, and overt prosocial behavior. Using a multimethod approach, we explored the links between the Big Five dimensions of personality and prosocial responding. Across three studies, we found that agreeableness was the dimension of personality most closely associated with emotional reactions to victims in need of help, and subsequent decisions to help those individuals. Results suggest that prosocial processes, including emotions, cognitions, and behaviors, may be part of a more general motivational process linked to personality. © 2016 by the Society for Personality and Social Psychology, Inc.

  9. Discovery of Cationic Polymers for Non-viral Gene Delivery using Combinatorial Approaches

    Science.gov (United States)

    Barua, Sutapa; Ramos, James; Potta, Thrimoorthy; Taylor, David; Huang, Huang-Chiao; Montanez, Gabriela; Rege, Kaushal

    2015-01-01

    Gene therapy is an attractive treatment option for diseases of genetic origin, including several cancers and cardiovascular diseases. While viruses are effective vectors for delivering exogenous genes to cells, concerns related to insertional mutagenesis, immunogenicity, lack of tropism, decay and high production costs necessitate the discovery of non-viral methods. Significant efforts have been focused on cationic polymers as non-viral alternatives for gene delivery. Recent studies have employed combinatorial syntheses and parallel screening methods for enhancing the efficacy of gene delivery, biocompatibility of the delivery vehicle, and overcoming cellular level barriers as they relate to polymer-mediated transgene uptake, transport, transcription, and expression. This review summarizes and discusses recent advances in combinatorial syntheses and parallel screening of cationic polymer libraries for the discovery of efficient and safe gene delivery systems. PMID:21843141

  10. Study on predicting residual life of elevator links by fracture mechanics approach

    Energy Technology Data Exchange (ETDEWEB)

    Li Helin; Zhang Yi; Deng Zengjie [China National Petroleum Corp., Xi`an, Shaanxi (China). Tubular Goods Research Center; Jin Dazeng [Xi`an Jiaotong Univ., Xi`an, Shaanxi (China)

    1995-12-31

    On the basis of investigation, failure and fracture analysis of elevator links, residual life prediction of links using fracture mechanics approach is studied, and mechanical properties, fracture toughness value K{sub IC} and fatigue crack propagation rage da/dN of the steel for elevator links are determined. Using the relation between stress intensity factor K{sub I} and the strain-energy release rate, the two-dimensional conversion thickness finite element method has been used to calculate the stress intensity factors K{sub I} for dangerous sections in the ring part of links. Furthermore, the reliability of calculations of the finite element stress intensity factors K{sub I} for dangerous sections of elevator links and the residual life computation for links are verified by fatigue tests of actual links. Finally, the experimental verification of computed results by 150T link fractured at site indicates that the computed critical crack lengths and residual life tally well with those measured and meet the needs of oil drilling.

  11. A SURVEY ON OPTIMIZATION APPROACHES TO SEMANTIC SERVICE DISCOVERY TOWARDS AN INTEGRATED SOLUTION

    Directory of Open Access Journals (Sweden)

    Chellammal Surianarayanan

    2012-07-01

    Full Text Available The process of semantic service discovery using an ontology reasoner such as Pellet is time consuming. This restricts the usage of web services in real time applications having dynamic composition requirements. As performance of semantic service discovery is crucial in service composition, it should be optimized. Various optimization methods are being proposed to improve the performance of semantic discovery. In this work, we investigate the existing optimization methods and broadly classify optimization mechanisms into two categories, namely optimization by efficient reasoning and optimization by efficient matching. Optimization by efficient matching is further classified into subcategories such as optimization by clustering, optimization by inverted indexing, optimization by caching, optimization by hybrid methods, optimization by efficient data structures and optimization by efficient matching algorithms. With a detailed study of different methods, an integrated optimization infrastructure along with matching method has been proposed to improve the performance of semantic matching component. To achieve better optimization the proposed method integrates the effects of caching, clustering and indexing. Theoretical aspects of performance evaluation of the proposed method are discussed.

  12. Handling Neighbor Discovery and Rendezvous Consistency with Weighted Quorum-Based Approach.

    Science.gov (United States)

    Own, Chung-Ming; Meng, Zhaopeng; Liu, Kehan

    2015-09-03

    Neighbor discovery and the power of sensors play an important role in the formation of Wireless Sensor Networks (WSNs) and mobile networks. Many asynchronous protocols based on wake-up time scheduling have been proposed to enable neighbor discovery among neighboring nodes for the energy saving, especially in the difficulty of clock synchronization. However, existing researches are divided two parts with the neighbor-discovery methods, one is the quorum-based protocols and the other is co-primality based protocols. Their distinction is on the arrangements of time slots, the former uses the quorums in the matrix, the latter adopts the numerical analysis. In our study, we propose the weighted heuristic quorum system (WQS), which is based on the quorum algorithm to eliminate redundant paths of active slots. We demonstrate the specification of our system: fewer active slots are required, the referring rate is balanced, and remaining power is considered particularly when a device maintains rendezvous with discovered neighbors. The evaluation results showed that our proposed method can effectively reschedule the active slots and save the computing time of the network system.

  13. Handling Neighbor Discovery and Rendezvous Consistency with Weighted Quorum-Based Approach

    Directory of Open Access Journals (Sweden)

    Chung-Ming Own

    2015-09-01

    Full Text Available Neighbor discovery and the power of sensors play an important role in the formation of Wireless Sensor Networks (WSNs and mobile networks. Many asynchronous protocols based on wake-up time scheduling have been proposed to enable neighbor discovery among neighboring nodes for the energy saving, especially in the difficulty of clock synchronization. However, existing researches are divided two parts with the neighbor-discovery methods, one is the quorum-based protocols and the other is co-primality based protocols. Their distinction is on the arrangements of time slots, the former uses the quorums in the matrix, the latter adopts the numerical analysis. In our study, we propose the weighted heuristic quorum system (WQS, which is based on the quorum algorithm to eliminate redundant paths of active slots. We demonstrate the specification of our system: fewer active slots are required, the referring rate is balanced, and remaining power is considered particularly when a device maintains rendezvous with discovered neighbors. The evaluation results showed that our proposed method can effectively reschedule the active slots and save the computing time of the network system.

  14. Dual-acting of Hybrid Compounds - A New Dawn in the Discovery of Multi-target Drugs: Lead Generation Approaches.

    Science.gov (United States)

    Abdolmaleki, Azizeh; Ghasemi, Jahan B

    2017-01-01

    Finding high quality beginning compounds is a critical job at the start of the lead generation stage for multi-target drug discovery (MTDD). Designing hybrid compounds as selective multitarget chemical entity is a challenge, opportunity, and new idea to better act against specific multiple targets. One hybrid molecule is formed by two (or more) pharmacophore group's participation. So, these new compounds often exhibit two or more activities going about as multi-target drugs (mtdrugs) and may have superior safety or efficacy. Application of integrating a range of information and sophisticated new in silico, bioinformatics, structural biology, pharmacogenomics methods may be useful to discover/design, and synthesis of the new hybrid molecules. In this regard, many rational and screening approaches have followed by medicinal chemists for the lead generation in MTDD. Here, we review some popular lead generation approaches that have been used for designing multiple ligands (DMLs). This paper focuses on dual- acting chemical entities that incorporate a part of two drugs or bioactive compounds to compose hybrid molecules. Also, it presents some of key concepts and limitations/strengths of lead generation methods by comparing combination framework method with screening approaches. Besides, a number of examples to represent applications of hybrid molecules in the drug discovery are included. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Identifying the Critical Links in Road Transportation Networks: Centrality-based approach utilizing structural properties

    Energy Technology Data Exchange (ETDEWEB)

    Chinthavali, Supriya [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-04-01

    Surface transportation road networks share structural properties similar to other complex networks (e.g., social networks, information networks, biological networks, and so on). This research investigates the structural properties of road networks for any possible correlation with the traffic characteristics such as link flows those determined independently. Additionally, we define a criticality index for the links of the road network that identifies the relative importance in the network. We tested our hypotheses with two sample road networks. Results show that, correlation exists between the link flows and centrality measures of a link of the road (dual graph approach is followed) and the criticality index is found to be effective for one test network to identify the vulnerable nodes.

  16. The NCAR Research Data Archive's Hybrid Approach for Data Discovery and Access

    Science.gov (United States)

    Schuster, D.; Worley, S. J.

    2013-12-01

    The NCAR Research Data Archive (RDA http://rda.ucar.edu) maintains a variety of data discovery and access capabilities for it's 600+ dataset collections to support the varying needs of a diverse user community. In-house developed and standards-based community tools offer services to more than 10,000 users annually. By number of users the largest group is external and access the RDA through web based protocols; the internal NCAR HPC users are fewer in number, but typically access more data volume. This paper will detail the data discovery and access services maintained by the RDA to support both user groups, and show metrics that illustrate how the community is using the services. The distributed search capability enabled by standards-based community tools, such as Geoportal and an OAI-PMH access point that serves multiple metadata standards, provide pathways for external users to initially discover RDA holdings. From here, in-house developed web interfaces leverage primary discovery level metadata databases that support keyword and faceted searches. Internal NCAR HPC users, or those familiar with the RDA, may go directly to the dataset collection of interest and refine their search based on rich file collection metadata. Multiple levels of metadata have proven to be invaluable for discovery within terabyte-sized archives composed of many atmospheric or oceanic levels, hundreds of parameters, and often numerous grid and time resolutions. Once users find the data they want, their access needs may vary as well. A THREDDS data server running on targeted dataset collections enables remote file access through OPENDAP and other web based protocols primarily for external users. In-house developed tools give all users the capability to submit data subset extraction and format conversion requests through scalable, HPC based delayed mode batch processing. Users can monitor their RDA-based data processing progress and receive instructions on how to access the data when it is

  17. Acetone-Linked Peptides: A Convergent Approach for Peptide Macrocyclization and Labeling.

    Science.gov (United States)

    Assem, Naila; Ferreira, David J; Wolan, Dennis W; Dawson, Philip E

    2015-07-20

    Macrocyclization is a broadly applied approach for overcoming the intrinsically disordered nature of linear peptides. Herein, it is shown that dichloroacetone (DCA) enhances helical secondary structures when introduced between peptide nucleophiles, such as thiols, to yield an acetone-linked bridge (ACE). Aside from stabilizing helical structures, the ketone moiety embedded in the linker can be modified with diverse molecular tags by oxime ligation. Insights into the structure of the tether were obtained through co-crystallization of a constrained S-peptide in complex with RNAse S. The scope of the acetone-linked peptides was further explored through the generation of N-terminus to side chain macrocycles and a new approach for generating fused macrocycles (bicycles). Together, these studies suggest that acetone linking is generally applicable to peptide macrocycles with a specific utility in the synthesis of stabilized helices that incorporate functional tags. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Current approaches for the discovery of drugs that deter substance and drug abuse.

    Science.gov (United States)

    Yasgar, Adam; Simeonov, Anton

    2014-11-01

    Much has been presented and debated on the topic of drug abuse and its multidimensional nature, including the role of society and its customs and laws, economical factors, and the magnitude and nature of the burden. Given the complex nature of the receptors and pathways implicated in regulation of the cognitive and behavioral processes associated with addiction, a large number of molecular targets have been interrogated during recent years to discover starting points for development of small-molecule interventions. This review describes recent developments in the field of early drug discovery for drug abuse interventions with an emphasis on the advances published during the 2012 - 2014 period. Technologically, the processes/platforms utilized in drug abuse drug discovery are nearly identical to those used in the other disease areas. A key complicating factor in drug abuse research is the enormous biological complexity surrounding the brain processes involved and the associated difficulty in finding 'good' targets and achieving exquisite selectivity of treatment agents. While tremendous progress has been made during recent years to use the power of high-throughput technologies to discover proof-of-principle molecules for many new targets, next-generation models will be especially important in this field. Examples include: seeking advantageous drug-drug combinations, the use of automated whole-animal behavioral screening systems, advancing our understanding of the role of epigenetics in drug addiction and the employment of organoid-level 3D test platforms (also referred to as tissue-chip or organs-on-chip).

  19. 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.

  20. Discovery and characterization of a Higgs-like resonance using the Matrix Element Likelihood Approach

    Energy Technology Data Exchange (ETDEWEB)

    Whitbeck, Andrew J. [Johns Hopkins Univ., Baltimore, MD (United States)

    2013-09-01

    Understanding the exact mechanism of electroweak symmetry breaking through the discovery and characterization of the Higgs boson is one of the primary goals of the Large Hadron Collider (LHC). Two searches for a Higgs boson decaying to a pair of Z bosons with subsequent decays to either 2ℓ2q or 4ℓ are presented using data recorded with the Compact Muon Solenoid (CMS). The discovery and characterization of a Higgs-like resonance using a new set of tools is reported. The foundations of such tools are developed and prospects for their use in other Higgs channels and at future colliders are addressed. Although the Standard Model (SM) of electroweak interactions has been extremely successful in describing a number of phenomena, there are still questions to be addressed pertaining to its naturalness and its possible connection to beyond the SM physics. Results are interpreted in the context of possible extensions to the SM and their effect on our understanding of the universe.

  1. From Mollusks to Medicine: A Venomics Approach for the Discovery and Characterization of Therapeutics from Terebridae Peptide Toxins

    Directory of Open Access Journals (Sweden)

    Aida Verdes

    2016-04-01

    Full Text Available Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1 delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2 identification and classification of putative teretoxins through omics methodologies, including genomics, transcriptomics, and proteomics; (3 chemical and recombinant synthesis of promising peptide toxins; (4 structural characterization through experimental and computational methods; (5 determination of teretoxin bioactivity and molecular function through biological assays and computational modeling; (6 optimization of peptide toxin affinity and selectivity to molecular target; and (7 development of strategies for effective delivery of venom peptide therapeutics. While our research focuses on terebrids, the venomics approach outlined here can be applied to the discovery and characterization of peptide toxins from any venomous taxa.

  2. Beyond human error taxonomies in assessment of risk in sociotechnical systems: a new paradigm with the EAST 'broken-links' approach.

    Science.gov (United States)

    Stanton, Neville A; Harvey, Catherine

    2017-02-01

    Risk assessments in Sociotechnical Systems (STS) tend to be based on error taxonomies, yet the term 'human error' does not sit easily with STS theories and concepts. A new break-link approach was proposed as an alternative risk assessment paradigm to reveal the effect of information communication failures between agents and tasks on the entire STS. A case study of the training of a Royal Navy crew detecting a low flying Hawk (simulating a sea-skimming missile) is presented using EAST to model the Hawk-Frigate STS in terms of social, information and task networks. By breaking 19 social links and 12 task links, 137 potential risks were identified. Discoveries included revealing the effect of risk moving around the system; reducing the risks to the Hawk increased the risks to the Frigate. Future research should examine the effects of compounded information communication failures on STS performance. Practitioner Summary: The paper presents a step-by-step walk-through of EAST to show how it can be used for risk assessment in sociotechnical systems. The 'broken-links' method takes a systemic, rather than taxonomic, approach to identify information communication failures in social and task networks.

  3. A Knowledge Discovery Approach to Diagnosing Intracranial Hematomas on Brain CT: Recognition, Measurement and Classification

    Science.gov (United States)

    Liao, Chun-Chih; Xiao, Furen; Wong, Jau-Min; Chiang, I.-Jen

    Computed tomography (CT) of the brain is preferred study on neurological emergencies. Physicians use CT to diagnose various types of intracranial hematomas, including epidural, subdural and intracerebral hematomas according to their locations and shapes. We propose a novel method that can automatically diagnose intracranial hematomas by combining machine vision and knowledge discovery techniques. The skull on the CT slice is located and the depth of each intracranial pixel is labeled. After normalization of the pixel intensities by their depth, the hyperdense area of intracranial hematoma is segmented with multi-resolution thresholding and region-growing. We then apply C4.5 algorithm to construct a decision tree using the features of the segmented hematoma and the diagnoses made by physicians. The algorithm was evaluated on 48 pathological images treated in a single institute. The two discovered rules closely resemble those used by human experts, and are able to make correct diagnoses in all cases.

  4. Target discovery focused approaches to overcome bottlenecks in the exploitation of antimycobacterial natural products.

    Science.gov (United States)

    Baptista, Rafael; Bhowmick, Sumana; Nash, Robert J; Baillie, Les; Mur, Luis Aj

    2018-04-01

    Tuberculosis is a major global health hazard. The search for new antimycobacterials has focused on such as screening combinational chemistry libraries or designing chemicals to target predefined pockets of essential bacterial proteins. The relative ineffectiveness of these has led to a reappraisal of natural products for new antimycobacterial drug leads. However, progress has been limited, we suggest through a failure in many cases to define the drug target and optimize the hits using this information. We highlight methods of target discovery needed to develop a drug into a candidate for clinical trials. We incorporate these into suggested analysis pipelines which could inform the research strategies to accelerate the development of new drug leads from natural products.

  5. Open-access public-private partnerships to enable drug discovery--new approaches.

    Science.gov (United States)

    Müller, Susanne; Weigelt, Johan

    2010-03-01

    The productivity of the pharmaceutical industry, as assessed by the number of NMEs produced per US dollar spent in R&D, has been in steady decline during the past 40 years. This decline in productivity not only poses a significant challenge to the pharmaceutical industry, but also to society because of the importance of developing drugs for the treatment of unmet medical needs. The major challenge in progressing a new drug to the market is the successful completion of clinical trials. However, the failure rate of drugs entering trials has not decreased, despite various technological and scientific breakthroughs in recent decades, and despite intense target validation efforts. This lack of success suggests limitations in the fundamental understanding of target biology and human pharmacology. One contributing factor may be the traditional secrecy of the pharmaceutical sector, a characteristic that does not promote scientific discovery in an optimal manner. Access to broader knowledge relating to target biology and human pharmacology is difficult to obtain because interactions between researchers in industry and academia are typically restricted to closed collaborations in which the knowledge gained is confidential.However, open-access collaborative partnerships are gaining momentum in industry, and are also favored by funding agencies. Such open-access collaborations may be a powerful alternative to closed collaborations; the sharing of early-stage research data is expected to enable scientific discovery by engaging a broader section of the scientific community in the exploration of new findings. Potentially, the sharing of data could contribute to an increased understanding of biological processes and a decrease in the attrition of clinical programs.

  6. Link Performance Analysis and monitoring - A unified approach to divergent requirements

    Science.gov (United States)

    Thom, G. A.

    Link Performance Analysis and real-time monitoring are generally covered by a wide range of equipment. Bit Error Rate testers provide digital link performance measurements but are not useful during real-time data flows. Real-time performance monitors utilize the fixed overhead content but vary widely from format to format. Link quality information is also present from signal reconstruction equipment in the form of receiver AGC, bit synchronizer AGC, and bit synchronizer soft decision level outputs, but no general approach to utilizing this information exists. This paper presents an approach to link tests, real-time data quality monitoring, and results presentation that utilizes a set of general purpose modules in a flexible architectural environment. The system operates over a wide range of bit rates (up to 150 Mbs) and employs several measurement techniques, including P/N code errors or fixed PCM format errors, derived real-time BER from frame sync errors, and Data Quality Analysis derived by counting significant sync status changes. The architecture performs with a minimum of elements in place to permit a phased update of the user's unit in accordance with his needs.

  7. Link removal for the control of stochastically evolving epidemics over networks: a comparison of approaches.

    Science.gov (United States)

    Enns, Eva A; Brandeau, Margaret L

    2015-04-21

    For many communicable diseases, knowledge of the underlying contact network through which the disease spreads is essential to determining appropriate control measures. When behavior change is the primary intervention for disease prevention, it is important to understand how to best modify network connectivity using the limited resources available to control disease spread. We describe and compare four algorithms for selecting a limited number of links to remove from a network: two "preventive" approaches (edge centrality, R0 minimization), where the decision of which links to remove is made prior to any disease outbreak and depends only on the network structure; and two "reactive" approaches (S-I edge centrality, optimal quarantining), where information about the initial disease states of the nodes is incorporated into the decision of which links to remove. We evaluate the performance of these algorithms in minimizing the total number of infections that occur over the course of an acute outbreak of disease. We consider different network structures, including both static and dynamic Erdös-Rényi random networks with varying levels of connectivity, a real-world network of residential hotels connected through injection drug use, and a network exhibiting community structure. We show that reactive approaches outperform preventive approaches in averting infections. Among reactive approaches, removing links in order of S-I edge centrality is favored when the link removal budget is small, while optimal quarantining performs best when the link removal budget is sufficiently large. The budget threshold above which optimal quarantining outperforms the S-I edge centrality algorithm is a function of both network structure (higher for unstructured Erdös-Rényi random networks compared to networks with community structure or the real-world network) and disease infectiousness (lower for highly infectious diseases). We conduct a value-of-information analysis of knowing which

  8. Rational Discovery of (+) (S) Abscisic Acid as a Potential Antifungal Agent: a Repurposing Approach.

    Science.gov (United States)

    Khedr, Mohammed A; Massarotti, Alberto; Mohamed, Maged E

    2018-06-04

    Fungal infections are spreading widely worldwide, and the types of treatment are limited due to the lack of diverse therapeutic agents and their associated side effects and toxicity. The discovery of new antifungal classes is vital and critical. We discovered the antifungal activity of abscisic acid through a rational drug design methodology that included the building of homology models for fungal chorismate mutases and a pharmacophore model derived from a transition state inhibitor. Ligand-based virtual screening resulted in some hits that were filtered using molecular docking and molecular dynamic simulations studies. Both in silico methods and in vitro antifungal assays were used as tools to select and validate the abscisic acid repurposing. Abscisic acid inhibition assays confirmed the inhibitory effect of abscisic acid on chorismate mutase through the inhibition of phenylpyruvate production. The repositioning of abscisic acid, the well-known and naturally occurring plant growth regulator, as a potential antifungal agent because of its suggested action as an inhibitor to several fungal chorismate mutases was the main result of this work.

  9. A Novel Approach to Discovery and Image Access in the Petabyte Age

    Science.gov (United States)

    Mueller, D.; Dimitoglou, G.; Alexanderian, A.; Garcia Ortiz, J.; Schmidt, L.; Hughitt, V. K.; Ireland, J.; Fleck, B.

    2009-12-01

    Space missions generate an ever-growing amount of data, as impressively highlighted by the Solar Dynamics Observatory's expected data rate of 1.4 Terabyte per day. In order to fully exploit their data, scientists need to be able to browse and visualize many different data products spanning a large range of physical length and time scales. So far, the tools available to the scientific community either require downloading all potentially relevant data sets beforehand in their entirety or provide only movies with a fixed resolution and cadence. To facilitate browsing and analysis of complex time-dependent data sets from multiple sources, we are developing JHelioviewer, a JPEG 2000-based visualization and discovery infrastructure for image data. Currently focused on solar physics data, it can easily be adapted for use in other areas of space and earth sciences. Together with its web-based counterpart helioviewer.org, JHelioviewer offers intuitive ways to browse large amounts of heterogeneous data remotely and allows users to search related event data bases. The user interface for JHelioviewer is a multi-platform Java client that can both communicate with a remote server via the JPEG 2000 interactive protocol JPIP and open local data. The random code stream access of JPIP minimizes data transfer and can encapsulate meta data as well as multiple image channels in one data stream. This presentation will illustrate some of the features of JHelioviewer and the advantages of JPEG 2000 as a new data compression standard.

  10. A Novel Approach to Discovery and Access to Solar Data in the Petabyte Age

    Science.gov (United States)

    Mueller, Daniel; Dimitoglou, G.; Hughitt, V. K.; Ireland, J.; Wamsler, B.; Fleck, B.

    2009-05-01

    Space missions generate an ever-growing amount of data, as impressively highlighted by SDO's expected data rate of 1.4 TByte/day. In order to fully exploit their data, scientists need to be able to browse and visualize many different data products spanning a large range of physical length and time scales. So far, the tools available to the scientific community either require downloading all potentially relevant data sets beforehand in their entirety or provide only movies with a fixed resolution and cadence. To facilitate browsing and analysis of complex time-dependent data sets from multiple sources, we are developing JHelioviewer, a JPEG 2000-based visualization and discovery infrastructure for solar image data. Together with its web-based counterpart helioviewer.org, JHelioviewer offers intuitive ways to browse large amounts of heterogeneous data remotely and allows users to search related event data bases. The user interface for JHelioviewer is a multi-platform Java client that can both communicate with a remote server via the JPEG 2000 interactive protocol JPIP and open local data. The random code stream access of JPIP minimizes data transfer and can encapsulate meta data as well as multiple image channels in one data stream. This presentation will illustrate some of the features of JHelioviewer and the advantages of JPEG 2000 as a new data compression standard.

  11. Phenotypic Screening Approaches to Develop Aurora Kinase Inhibitors: Drug Discovery Perspectives.

    Science.gov (United States)

    Marugán, Carlos; Torres, Raquel; Lallena, María José

    2015-01-01

    Targeting mitotic regulators as a strategy to fight cancer implies the development of drugs against key proteins, such as Aurora-A and -B. Current drugs, which target mitosis through a general mechanism of action (stabilization/destabilization of microtubules), have several side effects (neutropenia, alopecia, and emesis). Pharmaceutical companies aim at avoiding these unwanted effects by generating improved and selective drugs that increase the quality of life of the patients. However, the development of these drugs is an ambitious task that involves testing thousands of compounds through biochemical and cell-based assays. In addition, molecules usually target complex biological processes, involving several proteins and different molecular pathways, further emphasizing the need for high-throughput screening techniques and multiplexing technologies in order to identify drugs with the desired phenotype. We will briefly describe two multiplexing technologies [high-content imaging (HCI) and flow cytometry] and two key processes for drug discovery research (assay development and validation) following our own published industry quality standards. We will further focus on HCI as a useful tool for phenotypic screening and will provide a concrete example of HCI assay to detect Aurora-A or -B selective inhibitors discriminating the off-target effects related to the inhibition of other cell cycle or non-cell cycle key regulators. Finally, we will describe other assays that can help to characterize the in vitro pharmacology of the inhibitors.

  12. Gun possession among American youth: a discovery-based approach to understand gun violence.

    Science.gov (United States)

    Ruggles, Kelly V; Rajan, Sonali

    2014-01-01

    To apply discovery-based computational methods to nationally representative data from the Centers for Disease Control and Preventions' Youth Risk Behavior Surveillance System to better understand and visualize the behavioral factors associated with gun possession among adolescent youth. Our study uncovered the multidimensional nature of gun possession across nearly five million unique data points over a ten year period (2001-2011). Specifically, we automated odds ratio calculations for 55 risk behaviors to assemble a comprehensive table of associations for every behavior combination. Downstream analyses included the hierarchical clustering of risk behaviors based on their association "fingerprint" to 1) visualize and assess which behaviors frequently co-occur and 2) evaluate which risk behaviors are consistently found to be associated with gun possession. From these analyses, we identified more than 40 behavioral factors, including heroin use, using snuff on school property, having been injured in a fight, and having been a victim of sexual violence, that have and continue to be strongly associated with gun possession. Additionally, we identified six behavioral clusters based on association similarities: 1) physical activity and nutrition; 2) disordered eating, suicide and sexual violence; 3) weapon carrying and physical safety; 4) alcohol, marijuana and cigarette use; 5) drug use on school property and 6) overall drug use. Use of computational methodologies identified multiple risk behaviors, beyond more commonly discussed indicators of poor mental health, that are associated with gun possession among youth. Implications for prevention efforts and future interdisciplinary work applying computational methods to behavioral science data are described.

  13. DenguePredict: An Integrated Drug Repositioning Approach towards Drug Discovery for Dengue.

    Science.gov (United States)

    Wang, QuanQiu; Xu, Rong

    2015-01-01

    Dengue is a viral disease of expanding global incidence without cures. Here we present a drug repositioning system (DenguePredict) leveraging upon a unique drug treatment database and vast amounts of disease- and drug-related data. We first constructed a large-scale genetic disease network with enriched dengue genetics data curated from biomedical literature. We applied a network-based ranking algorithm to find dengue-related diseases from the disease network. We then developed a novel algorithm to prioritize FDA-approved drugs from dengue-related diseases to treat dengue. When tested in a de-novo validation setting, DenguePredict found the only two drugs tested in clinical trials for treating dengue and ranked them highly: chloroquine ranked at top 0.96% and ivermectin at top 22.75%. We showed that drugs targeting immune systems and arachidonic acid metabolism-related apoptotic pathways might represent innovative drugs to treat dengue. In summary, DenguePredict, by combining comprehensive disease- and drug-related data and novel algorithms, may greatly facilitate drug discovery for dengue.

  14. Phenotypic screening approaches to develop Aurora kinase inhibitors: Drug Discovery perspectives

    Directory of Open Access Journals (Sweden)

    Carlos eMarugán

    2016-01-01

    Full Text Available Targeting mitotic regulators as a strategy to fight cancer implies the development of drugs against key proteins such as Aurora A and B. Current drugs which target mitosis through a general mechanism of action (stabilization/destabilization of microtubules, have several side effects (neutropenia, alopecia, emesis. Pharmaceutical companies aim at avoiding these unwanted effects by generating improved and selective drugs that increase the quality of life of the patients. However, the development of these drugs is an ambitious task that involves testing thousands of compounds through biochemical and cell-based assays. In addition, molecules usually target complex biological processes, involving several proteins and different molecular pathways, further emphasizing the need for high-throughput screening techniques and multiplexing technologies in order to identify drugs with the desired phenotype.We will briefly describe two multiplexing technologies (high-content imaging, microarrays and flow cytometry and two key processes for drug discovery research (assay development and validation following our own published industry quality standards. We will further focus on high-content imaging as a useful tool for phenotypic screening and will provide a concrete example of high-content imaging assay to detect Aurora A or B selective inhibitors discriminating the off-target effects related to inhibition of other cell cycle or non-cell cycle key regulators. Finally, we will describe other assays that can help to characterize the in vitro pharmacology of the inhibitors.

  15. diceR: an R package for class discovery using an ensemble driven approach.

    Science.gov (United States)

    Chiu, Derek S; Talhouk, Aline

    2018-01-15

    Given a set of features, researchers are often interested in partitioning objects into homogeneous clusters. In health research, cancer research in particular, high-throughput data is collected with the aim of segmenting patients into sub-populations to aid in disease diagnosis, prognosis or response to therapy. Cluster analysis, a class of unsupervised learning techniques, is often used for class discovery. Cluster analysis suffers from some limitations, including the need to select up-front the algorithm to be used as well as the number of clusters to generate, in addition, there may exist several groupings consistent with the data, making it very difficult to validate a final solution. Ensemble clustering is a technique used to mitigate these limitations and facilitate the generalization and reproducibility of findings in new cohorts of patients. We introduce diceR (diverse cluster ensemble in R), a software package available on CRAN: https://CRAN.R-project.org/package=diceR CONCLUSIONS: diceR is designed to provide a set of tools to guide researchers through a general cluster analysis process that relies on minimizing subjective decision-making. Although developed in a biological context, the tools in diceR are data-agnostic and thus can be applied in different contexts.

  16. Nonlinear degradation of a visible-light communication link: A Volterra-series approach

    Science.gov (United States)

    Kamalakis, Thomas; Dede, Georgia

    2018-06-01

    Visible light communications can be used to provide illumination and data communication at the same time. In this paper, a reverse-engineering approach is presented for assessing the impact of nonlinear signal distortion in visible light communication links. The approach is based on the Volterra series expansion and has the advantage of accurately accounting for memory effects in contrast to the static nonlinear models that are popular in the literature. Volterra kernels describe the end-to-end system response and can be inferred from measurements. Consequently, this approach does not rely on any particular physical models and assumptions regarding the individual link components. We provide the necessary framework for estimating the nonlinear distortion on the symbol estimates of a discrete multitone modulated link. Various design aspects such as waveform clipping and predistortion are also incorporated in the analysis. Using this framework, the nonlinear signal-to-interference is calculated for the system at hand. It is shown that at high signal amplitudes, the nonlinear signal-to-interference can be less than 25 dB.

  17. Building policy capacities: an interactive approach for linking knowledge to action in health promotion.

    Science.gov (United States)

    Rütten, Alfred; Gelius, Peter

    2014-09-01

    This article outlines a theoretical framework for an interactive, research-driven approach to building policy capacities in health promotion. First, it illustrates how two important issues in the recent public health debate, capacity building and linking scientific knowledge to policy action, are connected to each other theoretically. It then introduces an international study on an interactive approach to capacity building in health promotion policy. The approach combines the ADEPT model of policy capacities with a co-operative planning process to foster the exchange of knowledge between policy-makers and researchers, thus improving intra- and inter-organizational capacities. A regional-level physical activity promotion project involving governmental and public-law institutions, NGOs and university researchers serves as a case study to illustrate the potential of the approach for capacity building. Analysis and comparison with a similar local-level project indicate that the approach provides an effective means of linking scientific knowledge to policy action and to planning concrete measures for capacity building in health promotion, but that it requires sufficiently long timelines and adequate resources to achieve adequate implementation and sustainability. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Drug discovery for male subfertility using high-throughput screening: a new approach to an unsolved problem.

    Science.gov (United States)

    Martins da Silva, Sarah J; Brown, Sean G; Sutton, Keith; King, Louise V; Ruso, Halil; Gray, David W; Wyatt, Paul G; Kelly, Mark C; Barratt, Christopher L R; Hope, Anthony G

    2017-05-01

    Can pharma drug discovery approaches be utilized to transform investigation into novel therapeutics for male infertility? High-throughput screening (HTS) is a viable approach to much-needed drug discovery for male factor infertility. There is both huge demand and a genuine clinical need for new treatment options for infertile men. However, the time, effort and resources required for drug discovery are currently exorbitant, due to the unique challenges of the cellular, physical and functional properties of human spermatozoa and a lack of appropriate assay platform. Spermatozoa were obtained from healthy volunteer research donors and subfertile patients undergoing IVF/ICSI at a hospital-assisted reproductive techniques clinic between January 2012 and November 2016. A HTS assay was developed and validated using intracellular calcium ([Ca2+]i) as a surrogate for motility in human spermatozoa. Calcium fluorescence was detected using a Flexstation microplate reader (384-well platform) and compared with responses evoked by progesterone, a compound known to modify a number of biologically relevant behaviours in human spermatozoa. Hit compounds identified following single point drug screen (10 μM) of an ion channel-focussed library assembled by the University of Dundee Drug Discovery Unit were rescreened to ensure potency using standard 10 point half-logarithm concentration curves, and tested for purity and integrity using liquid chromatography and mass spectrometry. Hit compounds were grouped by structure activity relationships and five representative compounds then further investigated for direct effects on spermatozoa, using computer-assisted sperm assessment, sperm penetration assay and whole-cell patch clamping. Of the 3242 ion channel library ligands screened, 384 compounds (11.8%) elicited a statistically significant increase in calcium fluorescence, with greater than 3× median absolute deviation above the baseline. Seventy-four compounds eliciting ≥50% increase

  19. In silico approach for the discovery of new PPARγ modulators among plant-derived polyphenols

    Directory of Open Access Journals (Sweden)

    Encinar JA

    2015-11-01

    Full Text Available José Antonio Encinar,1 Gregorio Fernández-Ballester,1 Vicente Galiano-Ibarra,2 Vicente Micol1,3 1Molecular and Cell Biology Institute, 2Physics and Computer Architecture Department, Miguel Hernández University, Elche, Spain; 3CIBER: CB12/03/30038 Physiopathology of Obesity and Nutrition, CIBERobn, Instituto de Salud Carlos III, Palma de Mallorca, SpainAbstract: Peroxisome proliferator-activated receptor gamma (PPARγ is a well-characterized member of the PPAR family that is predominantly expressed in adipose tissue and plays a significant role in lipid metabolism, adipogenesis, glucose homeostasis, and insulin sensitization. Full agonists of synthetic thiazolidinediones (TZDs have been therapeutically used in clinical practice to treat type 2 diabetes for many years. Although it can effectively lower blood glucose levels and improve insulin sensitivity, the administration of TZDs has been associated with severe side effects. Based on recent evidence obtained with plant-derived polyphenols, the present in silico study aimed at finding new selective human PPARγ (hPPARγ modulators that are able to improve glucose homeostasis with reduced side effects compared with TZDs. Docking experiments have been used to select compounds with strong binding affinity (ΔG values ranging from -10.0±0.9 to -11.4±0.9 kcal/mol by docking against the binding site of several X-ray structures of hPPARγ. These putative modulators present several molecular interactions with the binding site of the protein. Additionally, most of the selected compounds have favorable druggability and good ADMET properties. These results aim to pave the way for further bench-scale analysis for the discovery of new modulators of hPPARγ that do not induce any side effects. Keywords: virtual screening, molecular docking, high-throughput computing, TZDs, human PPARγ, AutoDock/Vina, ADMET, phenolic compounds

  20. Gun possession among American youth: a discovery-based approach to understand gun violence.

    Directory of Open Access Journals (Sweden)

    Kelly V Ruggles

    Full Text Available OBJECTIVE: To apply discovery-based computational methods to nationally representative data from the Centers for Disease Control and Preventions' Youth Risk Behavior Surveillance System to better understand and visualize the behavioral factors associated with gun possession among adolescent youth. RESULTS: Our study uncovered the multidimensional nature of gun possession across nearly five million unique data points over a ten year period (2001-2011. Specifically, we automated odds ratio calculations for 55 risk behaviors to assemble a comprehensive table of associations for every behavior combination. Downstream analyses included the hierarchical clustering of risk behaviors based on their association "fingerprint" to 1 visualize and assess which behaviors frequently co-occur and 2 evaluate which risk behaviors are consistently found to be associated with gun possession. From these analyses, we identified more than 40 behavioral factors, including heroin use, using snuff on school property, having been injured in a fight, and having been a victim of sexual violence, that have and continue to be strongly associated with gun possession. Additionally, we identified six behavioral clusters based on association similarities: 1 physical activity and nutrition; 2 disordered eating, suicide and sexual violence; 3 weapon carrying and physical safety; 4 alcohol, marijuana and cigarette use; 5 drug use on school property and 6 overall drug use. CONCLUSIONS: Use of computational methodologies identified multiple risk behaviors, beyond more commonly discussed indicators of poor mental health, that are associated with gun possession among youth. Implications for prevention efforts and future interdisciplinary work applying computational methods to behavioral science data are described.

  1. A Bioinformatic Approach for the Discovery of Antiaging Effects of Baicalein from Scutellaria baicalensis Georgi.

    Science.gov (United States)

    Gao, Li; Duan, Dan-Dan; Zhang, Jian-Qin; Zhou, Yu-Zhi; Qin, Xue-Mei; Du, Guan-Hua

    2016-03-15

    Aging is one of the most complicated phenomena and is the main risk factor for age-related diseases. Based on the public aging-related gene data, we propose a computational approach to predict the antiaging activities of compounds. This approach integrates network pharmacology and target fishing methods with the aim of identifying a potential antiaging compound from Scutellaria baicalensis Georgi. Utilizing this approach and subsequent experimental validation, it was found that baicalein at concentrations of 0.04, 0.2, and 1 mg/mL extended the mean, median, and maximum life spans in Drosophila melanogaster. Particularly, 0.2 mg/mL baicalein extends the mean and median life spans in male flies by 19.80% and 25.64%, respectively. Meanwhile, it was discovered that baicalein improved fertility in flies. Baicalein exerts antiaging effects likely through attenuating oxidative stress, including increases of CAT activity and GSH level and decrease of GSSG level.

  2. Statistical approach To understand MALDI-TOFMS matrices : discovery and evaluation of new MALDI matrices

    NARCIS (Netherlands)

    Meier, M.A.R.; Adams, N.; Schubert, U.S.

    2007-01-01

    A statistical approach is described to better understand the role of the matrix during a MALDI-TOFMS expt. Potential matrix mols. were selected based on a rational exptl. design and subsequently screened in order to investigate whether a certain compd. can act as a matrix for synthetic polymers. The

  3. Novel CNS drug discovery and development approach: model-based integration to predict neuro-pharmacokinetics and pharmacodynamics.

    Science.gov (United States)

    de Lange, Elizabeth C M; van den Brink, Willem; Yamamoto, Yumi; de Witte, Wilhelmus E A; Wong, Yin Cheong

    2017-12-01

    CNS drug development has been hampered by inadequate consideration of CNS pharmacokinetic (PK), pharmacodynamics (PD) and disease complexity (reductionist approach). Improvement is required via integrative model-based approaches. Areas covered: The authors summarize factors that have played a role in the high attrition rate of CNS compounds. Recent advances in CNS research and drug discovery are presented, especially with regard to assessment of relevant neuro-PK parameters. Suggestions for further improvements are also discussed. Expert opinion: Understanding time- and condition dependent interrelationships between neuro-PK and neuro-PD processes is key to predictions in different conditions. As a first screen, it is suggested to use in silico/in vitro derived molecular properties of candidate compounds and predict concentration-time profiles of compounds in multiple compartments of the human CNS, using time-course based physiology-based (PB) PK models. Then, for selected compounds, one can include in vitro drug-target binding kinetics to predict target occupancy (TO)-time profiles in humans. This will improve neuro-PD prediction. Furthermore, a pharmaco-omics approach is suggested, providing multilevel and paralleled data on systems processes from individuals in a systems-wide manner. Thus, clinical trials will be better informed, using fewer animals, while also, needing fewer individuals and samples per individual for proof of concept in humans.

  4. From Medicinal Chemistry to Human Health: Current Approaches to Drug Discovery for Cancer and Neglected Tropical Diseases

    Directory of Open Access Journals (Sweden)

    LEONARDO G. FERREIRA

    2018-02-01

    Full Text Available ABSTRACT Scientific and technological breakthroughs have compelled the current players in drug discovery to increasingly incorporate knowledge-based approaches. This evolving paradigm, which has its roots attached to the recent advances in medicinal chemistry, molecular and structural biology, has unprecedentedly demanded the development of up-to-date computational approaches, such as bio- and chemo-informatics. These tools have been pivotal to catalyzing the ever-increasing amount of data generated by the molecular sciences, and to converting the data into insightful guidelines for use in the research pipeline. As a result, ligand- and structure-based drug design have emerged as key pathways to address the pharmaceutical industry’s striking demands for innovation. These approaches depend on a keen integration of experimental and molecular modeling methods to surmount the main challenges faced by drug candidates - in vivo efficacy, pharmacodynamics, metabolism, pharmacokinetics and safety. To that end, the Laboratório de Química Medicinal e Computacional (LQMC of the Universidade de São Paulo has developed forefront research on highly prevalent and life-threatening neglected tropical diseases and cancer. By taking part in global initiatives for pharmaceutical innovation, the laboratory has contributed to the advance of these critical therapeutic areas through the use of cutting-edge strategies in medicinal chemistry.

  5. Multiscale approach to link red blood cell dynamics, shear viscosity, and ATP release.

    Science.gov (United States)

    Forsyth, Alison M; Wan, Jiandi; Owrutsky, Philip D; Abkarian, Manouk; Stone, Howard A

    2011-07-05

    RBCs are known to release ATP, which acts as a signaling molecule to cause dilation of blood vessels. A reduction in the release of ATP from RBCs has been linked to diseases such as type II diabetes and cystic fibrosis. Furthermore, reduced deformation of RBCs has been correlated with myocardial infarction and coronary heart disease. Because ATP release has been linked to cell deformation, we undertook a multiscale approach to understand the links between single RBC dynamics, ATP release, and macroscopic viscosity all at physiological shear rates. Our experimental approach included microfluidics, ATP measurements using a bioluminescent reaction, and rheology. Using microfluidics technology with high-speed imaging, we visualize the deformation and dynamics of single cells, which are known to undergo motions such as tumbling, swinging, tanktreading, and deformation. We report that shear thinning is not due to cellular deformation as previously believed, but rather it is due to the tumbling-to-tanktreading transition. In addition, our results indicate that ATP release is constant at shear stresses below a threshold (3 Pa), whereas above the threshold ATP release is increased and accompanied by large cellular deformations. Finally, performing experiments with well-known inhibitors, we show that the Pannexin 1 hemichannel is the main avenue for ATP release both above and below the threshold, whereas, the cystic fibrosis transmembrane conductance regulator only contributes to deformation-dependent ATP release above the stress threshold.

  6. An efficient collaborative approach for black hole attack discovery and mitigating its impact in manet

    Science.gov (United States)

    Devipriya, K.; Ivy, B. Persis Urbana; Prabha, D.

    2018-04-01

    A mobile ad hoc network (MANET) is an assemblage of nodes composed of mobile devices coupled in various ways wirelessly which do not have any central administration. Each node in MANET cooperates in forwarding packets in the network. This type of collaboration incurs high cost but there exits nodes that declines to cooperate leading to selfish conduct of nodes which effects overall network performance. To discover the attacks caused by such nodes, a renowned mechanism using watchdog can be deployed. In infrastructure less network attack detection and reaction and high false positives, false negatives initiating black hole attack becomes major issue in watchdog. This paper put forward a collaborative approach for identifying such attacks in MANET. Through abstract analysis and extensive simulation of this approach, the detection time of misbehaved nodes is reduced and substantial enhancement in overhead and throughput is witnessed.

  7. Drug Discovery and Development of Type 2 Diabetes Mellitus: Modern-Integrative Medicinal Approach.

    Science.gov (United States)

    Ghosh, Debosree; Parida, Pratap

    2016-01-01

    Type 2 diabetes is a disorder of ages, which has become deadlier because of life style modification and adaptation in the modern world. Extensive sudy of the pathophysiology of diabetes has opened up various mysteries about the disease and has helped us to know and understand diabetes in a better manner. Presently, we know many minute details about the pathophysiology of diabetes mellitus and are thus well weaponed to fight against it. Treatment regime has been evolving daily. Besides the conventional anti-diabetic drugs, integrated medicinal approach for treating diabetes type 2 with a compact therapeutic approach consisting of various targeted treatments for individual symptoms associated with the disease are being tried currently. Diabetes associated complications like high blood pressure, hyperglycemia, microalbumuria, dyslipidemia, pro -coagulation, etc. are being targeted and dealt with individually in the integrative medicinal approach. The results are promising and thus ignite hope for a better and more successful handling of diabetes and diabetes related pathophysiological complications in near future.

  8. Improved Soluble ScFv ELISA Screening Approach for Antibody Discovery Using Phage Display Technology.

    Science.gov (United States)

    Tohidkia, Mohammad R; Sepehri, Maryam; Khajeh, Shirin; Barar, Jaleh; Omidi, Yadollah

    2017-09-01

    Phage display technology (PDT) is a powerful tool for the isolation of recombinant antibody (Ab) fragments. Using PDT, target molecule-specific phage-Ab clones are enriched through the "biopanning" process. The individual specific binders are screened by the monoclonal scFv enzyme-linked immunosorbent assay (ELISA) that may associate with inevitable false-negative results. Thus, in this study, three strategies were investigated for optimization of the scFvs screening using Tomlinson I and J libraries, including (1) optimizing the expression of functional scFvs, (2) improving the sensitivity of ELISA, and (3) preparing different samples containing scFvs. The expression of all scFv Abs was significantly enhanced when scFv clones were cultivated in the terrific broth (TB) medium at the optimum temperature of 30 °C. The protein A-conjugated with horseradish peroxidase (HRP) was found to be a well-suited reagent for the detection of Ag-bound scFvs in comparison with either anti-c-myc Ab or the mixing procedure. Based on our findings, it seems there is no universal media supplement for an improved expression of all scFvs derived from both Tomlinson I and J libraries. We thus propose that expression of scFv fragments in a microplate scale is largely dependent on a variety of parameters, in particular the scFv clones and relevant sequences.

  9. 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.

  10. Biomarker discovery in heterogeneous tissue samples -taking the in-silico deconfounding approach

    Directory of Open Access Journals (Sweden)

    Parida Shreemanta K

    2010-01-01

    Full Text Available Abstract Background For heterogeneous tissues, such as blood, measurements of gene expression are confounded by relative proportions of cell types involved. Conclusions have to rely on estimation of gene expression signals for homogeneous cell populations, e.g. by applying micro-dissection, fluorescence activated cell sorting, or in-silico deconfounding. We studied feasibility and validity of a non-negative matrix decomposition algorithm using experimental gene expression data for blood and sorted cells from the same donor samples. Our objective was to optimize the algorithm regarding detection of differentially expressed genes and to enable its use for classification in the difficult scenario of reversely regulated genes. This would be of importance for the identification of candidate biomarkers in heterogeneous tissues. Results Experimental data and simulation studies involving noise parameters estimated from these data revealed that for valid detection of differential gene expression, quantile normalization and use of non-log data are optimal. We demonstrate the feasibility of predicting proportions of constituting cell types from gene expression data of single samples, as a prerequisite for a deconfounding-based classification approach. Classification cross-validation errors with and without using deconfounding results are reported as well as sample-size dependencies. Implementation of the algorithm, simulation and analysis scripts are available. Conclusions The deconfounding algorithm without decorrelation using quantile normalization on non-log data is proposed for biomarkers that are difficult to detect, and for cases where confounding by varying proportions of cell types is the suspected reason. In this case, a deconfounding ranking approach can be used as a powerful alternative to, or complement of, other statistical learning approaches to define candidate biomarkers for molecular diagnosis and prediction in biomedicine, in

  11. Serious limitations of the QTL/Microarray approach for QTL gene discovery

    Directory of Open Access Journals (Sweden)

    Warden Craig H

    2010-07-01

    Full Text Available Abstract Background It has been proposed that the use of gene expression microarrays in nonrecombinant parental or congenic strains can accelerate the process of isolating individual genes underlying quantitative trait loci (QTL. However, the effectiveness of this approach has not been assessed. Results Thirty-seven studies that have implemented the QTL/microarray approach in rodents were reviewed. About 30% of studies showed enrichment for QTL candidates, mostly in comparisons between congenic and background strains. Three studies led to the identification of an underlying QTL gene. To complement the literature results, a microarray experiment was performed using three mouse congenic strains isolating the effects of at least 25 biometric QTL. Results show that genes in the congenic donor regions were preferentially selected. However, within donor regions, the distribution of differentially expressed genes was homogeneous once gene density was accounted for. Genes within identical-by-descent (IBD regions were less likely to be differentially expressed in chromosome 2, but not in chromosomes 11 and 17. Furthermore, expression of QTL regulated in cis (cis eQTL showed higher expression in the background genotype, which was partially explained by the presence of single nucleotide polymorphisms (SNP. Conclusions The literature shows limited successes from the QTL/microarray approach to identify QTL genes. Our own results from microarray profiling of three congenic strains revealed a strong tendency to select cis-eQTL over trans-eQTL. IBD regions had little effect on rate of differential expression, and we provide several reasons why IBD should not be used to discard eQTL candidates. In addition, mismatch probes produced false cis-eQTL that could not be completely removed with the current strains genotypes and low probe density microarrays. The reviewed studies did not account for lack of coverage from the platforms used and therefore removed genes

  12. 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

  13. Efficient Discovery of Novel Multicomponent Mixtures for Hydrogen Storage: A Combined Computational/Experimental Approach

    Energy Technology Data Exchange (ETDEWEB)

    Wolverton, Christopher [Northwestern Univ., Evanston, IL (United States). Dept. of Materials Science and Engineering; Ozolins, Vidvuds [Univ. of California, Los Angeles, CA (United States). Dept. of Materials Science and Engineering; Kung, Harold H. [Northwestern Univ., Evanston, IL (United States). Dept. of Chemical and Biological Engineering; Yang, Jun [Ford Scientific Research Lab., Dearborn, MI (United States); Hwang, Sonjong [California Inst. of Technology (CalTech), Pasadena, CA (United States). Dept. of Chemistry and Chemical Engineering; Shore, Sheldon [The Ohio State Univ., Columbus, OH (United States). Dept. of Chemistry and Biochemistry

    2016-11-28

    The objective of the proposed program is to discover novel mixed hydrides for hydrogen storage, which enable the DOE 2010 system-level goals. Our goal is to find a material that desorbs 8.5 wt.% H2 or more at temperatures below 85°C. The research program will combine first-principles calculations of reaction thermodynamics and kinetics with material and catalyst synthesis, testing, and characterization. We will combine materials from distinct categories (e.g., chemical and complex hydrides) to form novel multicomponent reactions. Systems to be studied include mixtures of complex hydrides and chemical hydrides [e.g. LiNH2+NH3BH3] and nitrogen-hydrogen based borohydrides [e.g. Al(BH4)3(NH3)3]. The 2010 and 2015 FreedomCAR/DOE targets for hydrogen storage systems are very challenging, and cannot be met with existing materials. The vast majority of the work to date has delineated materials into various classes, e.g., complex and metal hydrides, chemical hydrides, and sorbents. However, very recent studies indicate that mixtures of storage materials, particularly mixtures between various classes, hold promise to achieve technological attributes that materials within an individual class cannot reach. Our project involves a systematic, rational approach to designing novel multicomponent mixtures of materials with fast hydrogenation/dehydrogenation kinetics and favorable thermodynamics using a combination of state-of-the-art scientific computing and experimentation. We will use the accurate predictive power of first-principles modeling to understand the thermodynamic and microscopic kinetic processes involved in hydrogen release and uptake and to design new material/catalyst systems with improved properties. Detailed characterization and atomic-scale catalysis experiments will elucidate the effect of dopants and nanoscale catalysts in achieving fast kinetics and reversibility. And

  14. The In Situ Enzymatic Screening (ISES) Approach to Reaction Discovery and Catalyst Identification.

    Science.gov (United States)

    Swyka, Robert A; Berkowitz, David B

    2017-12-14

    The importance of discovering new chemical transformations and/or optimizing catalytic combinations has led to a flurry of activity in reaction screening. The in situ enzymatic screening (ISES) approach described here utilizes biological tools (enzymes/cofactors) to advance chemistry. The protocol interfaces an organic reaction layer with an adjacent aqueous layer containing reporting enzymes that act upon the organic reaction product, giving rise to a spectroscopic signal. ISES allows the experimentalist to rapidly glean information on the relative rates of a set of parallel organic/organometallic reactions under investigation, without the need to quench the reactions or draw aliquots. In certain cases, the real-time enzymatic readout also provides information on sense and magnitude of enantioselectivity and substrate specificity. This article contains protocols for single-well (relative rate) and double-well (relative rate/enantiomeric excess) ISES, in addition to a colorimetric ISES protocol and a miniaturized double-well procedure. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

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

    Science.gov (United States)

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

    2018-04-06

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

  16. Discovery of a small-molecule inhibitor of Dvl-CXXC5 interaction by computational approaches

    Science.gov (United States)

    Ma, Songling; Choi, Jiwon; Jin, Xuemei; Kim, Hyun-Yi; Yun, Ji-Hye; Lee, Weontae; Choi, Kang-Yell; No, Kyoung Tai

    2018-05-01

    The Wnt/β-catenin signaling pathway plays a significant role in the control of osteoblastogenesis and bone formation. CXXC finger protein 5 (CXXC5) has been recently identified as a negative feedback regulator of osteoblast differentiation through a specific interaction with Dishevelled (Dvl) protein. It was reported that targeting the Dvl-CXXC5 interaction could be a novel anabolic therapeutic target for osteoporosis. In this study, complex structure of Dvl PDZ domain and CXXC5 peptide was simulated with molecular dynamics (MD). Based on the structural analysis of binding modes of MD-simulated Dvl PDZ domain with CXXC5 peptide and crystal Dvl PDZ domain with synthetic peptide-ligands, we generated two different pharmacophore models and applied pharmacophore-based virtual screening to discover potent inhibitors of the Dvl-CXXC5 interaction for the anabolic therapy of osteoporosis. Analysis of 16 compounds selected by means of a virtual screening protocol yielded four compounds that effectively disrupted the Dvl-CXXC5 interaction in the fluorescence polarization assay. Potential compounds were validated by fluorescence spectroscopy and nuclear magnetic resonance. We successfully identified a highly potent inhibitor, BMD4722, which directly binds to the Dvl PDZ domain and disrupts the Dvl-CXXC5 interaction. Overall, CXXC5-Dvl PDZ domain complex based pharmacophore combined with various traditional and simple computational methods is a promising approach for the development of modulators targeting the Dvl-CXXC5 interaction, and the potent inhibitor BMD4722 could serve as a starting point to discover or design more potent and specific the Dvl-CXXC5 interaction disruptors.

  17. Discovery of a small-molecule inhibitor of Dvl-CXXC5 interaction by computational approaches.

    Science.gov (United States)

    Ma, Songling; Choi, Jiwon; Jin, Xuemei; Kim, Hyun-Yi; Yun, Ji-Hye; Lee, Weontae; Choi, Kang-Yell; No, Kyoung Tai

    2018-04-07

    The Wnt/β-catenin signaling pathway plays a significant role in the control of osteoblastogenesis and bone formation. CXXC finger protein 5 (CXXC5) has been recently identified as a negative feedback regulator of osteoblast differentiation through a specific interaction with Dishevelled (Dvl) protein. It was reported that targeting the Dvl-CXXC5 interaction could be a novel anabolic therapeutic target for osteoporosis. In this study, complex structure of Dvl PDZ domain and CXXC5 peptide was simulated with molecular dynamics (MD). Based on the structural analysis of binding modes of MD-simulated Dvl PDZ domain with CXXC5 peptide and crystal Dvl PDZ domain with synthetic peptide-ligands, we generated two different pharmacophore models and applied pharmacophore-based virtual screening to discover potent inhibitors of the Dvl-CXXC5 interaction for the anabolic therapy of osteoporosis. Analysis of 16 compounds selected by means of a virtual screening protocol yielded four compounds that effectively disrupted the Dvl-CXXC5 interaction in the fluorescence polarization assay. Potential compounds were validated by fluorescence spectroscopy and nuclear magnetic resonance. We successfully identified a highly potent inhibitor, BMD4722, which directly binds to the Dvl PDZ domain and disrupts the Dvl-CXXC5 interaction. Overall, CXXC5-Dvl PDZ domain complex based pharmacophore combined with various traditional and simple computational methods is a promising approach for the development of modulators targeting the Dvl-CXXC5 interaction, and the potent inhibitor BMD4722 could serve as a starting point to discover or design more potent and specific the Dvl-CXXC5 interaction disruptors.

  18. Transcriptome inference and systems approaches to polypharmacology and drug discovery in herbal medicine.

    Science.gov (United States)

    Li, Peng; Chen, Jianxin; Zhang, Wuxia; Fu, Bangze; Wang, Wei

    2017-01-04

    Herbal medicine is a concoction of numerous chemical ingredients, and it exhibits polypharmacological effects to act on multiple pharmacological targets, regulating different biological mechanisms and treating a variety of diseases. Thus, this complexity is impossible to deconvolute by the reductionist method of extracting one active ingredient acting on one biological target. To dissect the polypharmacological effects of herbal medicines and their underling pharmacological targets as well as their corresponding active ingredients. We propose a system-biology strategy that combines omics and bioinformatical methodologies for exploring the polypharmacology of herbal mixtures. The myocardial ischemia model was induced by Ameroid constriction of the left anterior descending coronary in Ba-Ma miniature pigs. RNA-seq analysis was utilized to find the differential genes induced by myocardial ischemia in pigs treated with formula QSKL. A transcriptome-based inference method was used to find the landmark drugs with similar mechanisms to QSKL. Gene-level analysis of RNA-seq data in QSKL-treated cases versus control animals yields 279 differential genes. Transcriptome-based inference methods identified 80 landmark drugs that covered nearly all drug classes. Then, based on the landmark drugs, 155 potential pharmacological targets and 57 indications were identified for QSKL. Our results demonstrate the power of a combined approach for exploring the pharmacological target and chemical space of herbal medicines. We hope that our method could enhance our understanding of the molecular mechanisms of herbal systems and further accelerate the exploration of the value of traditional herbal medicine systems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. A unified approach to linking experimental, statistical and computational analysis of spike train data.

    Directory of Open Access Journals (Sweden)

    Liang Meng

    Full Text Available A fundamental issue in neuroscience is how to identify the multiple biophysical mechanisms through which neurons generate observed patterns of spiking activity. In previous work, we proposed a method for linking observed patterns of spiking activity to specific biophysical mechanisms based on a state space modeling framework and a sequential Monte Carlo, or particle filter, estimation algorithm. We have shown, in simulation, that this approach is able to identify a space of simple biophysical models that were consistent with observed spiking data (and included the model that generated the data, but have yet to demonstrate the application of the method to identify realistic currents from real spike train data. Here, we apply the particle filter to spiking data recorded from rat layer V cortical neurons, and correctly identify the dynamics of an slow, intrinsic current. The underlying intrinsic current is successfully identified in four distinct neurons, even though the cells exhibit two distinct classes of spiking activity: regular spiking and bursting. This approach--linking statistical, computational, and experimental neuroscience--provides an effective technique to constrain detailed biophysical models to specific mechanisms consistent with observed spike train data.

  20. Parallel interconnect for a novel system approach to short distance high information transfer data links

    Science.gov (United States)

    Raskin, Glenn; Lebby, Michael S.; Carney, F.; Kazakia, M.; Schwartz, Daniel B.; Gaw, Craig A.

    1997-04-01

    The OPTOBUSTM family of products provides for high performance parallel interconnection utilizing optical links in a 10-bit wide bi-directional configuration. The link is architected to be 'transparent' in that it is totally asynchronous and dc coupled so that it can be treated as a perfect cable with extremely low skew and no losses. An optical link consists of two identical transceiver modules and a pair of connectorized 62.5 micrometer multi mode fiber ribbon cables. The OPTOBUSTM I link provides bi- directional functionality at 4 Gbps (400 Mbps per channel), while the OPTOBUSTM II link will offer the same capability at 8 Gbps (800 Mbps per channel). The transparent structure of the OPTOBUSTM links allow for an arbitrary data stream regardless of its structure. Both the OPTOBUSTM I and OPTOBUSTM II transceiver modules are packaged as partially populated 14 by 14 pin grid arrays (PGA) with optical receptacles on one side of the module. The modules themselves are composed of several elements; including passives, integrated circuits optoelectronic devices and optical interface units (OIUs) (which consist of polymer waveguides and a specially designed lead frame). The initial offering of the modules electrical interface utilizes differential CML. The CML line driver sinks 5 mA of current into one of two pins. When terminated with 50 ohm pull-up resistors tied to a voltage between VCC and VCC-2, the result is a differential swing of plus or minus 250 mV, capable of driving standard PECL I/Os. Future offerings of the OPTOBUSTM links will incorporate LVDS and PECL interfaces as well as CML. The integrated circuits are silicon based. For OPTOBUSTM I links, a 1.5 micrometer drawn emitter NPN bipolar process is used for the receiver and an enhanced 0.8 micrometer CMOS process for the laser driver. For OPTOBUSTM II links, a 0.8 micrometer drawn emitter NPN bipolar process is used for the receiver and the driver IC utilizes 0.8 micrometer BiCMOS technology. The OPTOBUSTM

  1. A knowledge discovery approach to explore some Sun/Earth's climate relationships

    Science.gov (United States)

    Pou, A.; Valdes, J.

    2009-09-01

    Delta O18/16 data would more readily respond to solar influences. This raises the suspicion that perhaps they do not only reflect temperatures but also solar activity, as well as other possible factors not directly related to atmospheric temperatures. These methodologies may be useful as exploratory tools, directing the attention to specific areas where further research should be required. This could be the case of the Delta O18/16 data, frequently considered to be a reliable and accurate proxy of temperatures. c) Another experiment was made using daily maximum temperatures from 10 Spanish meteorological stations for the period 1901-2005 [3]. Using a hybrid procedure (Differential Evolution and Fletcher-Reeves Classical Optimization) it was found that a subset was capable of preserving the 10-dimensional similarity when nonlinearly mapped into 1D. A daily index, F1 was applied to the whole dataset and grouped by years and transformed into a Kolmogorov-Smirnov dissimilarity matrix, space optimized and clustered giving the following landmarks: 1911-12, 1919-1920, 1960, 1973 and 1989. A visual comparison with the aa geomagnetic index may suggest a certain coupling with changes in the magnetic field behavior. The complexity of the patterns suggest that the possible relationships between Earth's climate and solar activity may occur in much more complex ways than just irradiance variations and simple linear correlations. REFERENCES: [1] Valdés, J.J., Bonham-Carter, G. " Time Dependent Neural Network Models For Detecting Changes of State in Complex Processes: Applications in Earth Sciences and Astronomy”. Neural Networks, vol 19, (2), pp 196-207, 2006. [2] Valdés, J., Pou, A. "Greenland Temperatures and Solar Activity: A Computational Intelligence Approach," Proceedings of the 2007 IEEE International Joint Conference on Neural Networks (IJCNN 2007). Orlando, Florida, USA. August 12-17, 2007. [3] Valdés, J., Pou, A., Orchard, B. "Characterization of Climatic Variations in

  2. Straightforward hit identification approach in fragment-based discovery of bromodomain-containing protein 4 (BRD4) inhibitors.

    Science.gov (United States)

    Borysko, Petro; Moroz, Yurii S; Vasylchenko, Oleksandr V; Hurmach, Vasyl V; Starodubtseva, Anastasia; Stefanishena, Natalia; Nesteruk, Kateryna; Zozulya, Sergey; Kondratov, Ivan S; Grygorenko, Oleksandr O

    2018-05-09

    A combination approach of a fragment screening and "SAR by catalog" was used for the discovery of bromodomain-containing protein 4 (BRD4) inhibitors. Initial screening of 3695-fragment library against bromodomain 1 of BRD4 using thermal shift assay (TSA), followed by initial hit validation, resulted in 73 fragment hits, which were used to construct a follow-up library selected from available screening collection. Additionally, analogs of inactive fragments, as well as a set of randomly selected compounds were also prepared (3 × 3200 compounds in total). Screening of the resulting sets using TSA, followed by re-testing at several concentrations, counter-screen, and TR-FRET assay resulted in 18 confirmed hits. Compounds derived from the initial fragment set showed better hit rate as compared to the other two sets. Finally, building dose-response curves revealed three compounds with IC 50  = 1.9-7.4 μM. For these compounds, binding sites and conformations in the BRD4 (4UYD) have been determined by docking. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

    Science.gov (United States)

    Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A

    2016-07-01

    A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ

  4. A Weakest-Link Approach for Fatigue Limit of 30CrNiMo8 Steels (Preprint)

    Science.gov (United States)

    2011-03-01

    34Application of a Weakest-Link Concept to the Fatigue Limit of the Bearing Steel Sae 52100 in a Bainitic Condition," Fatigue and Fracture of...AFRL-RX-WP-TP-2011-4206 A WEAKEST-LINK APPROACH FOR FATIGUE LIMIT OF 30CrNiMo8 STEELS (PREPRINT) S. Ekwaro-Osire and H.V. Kulkarni Texas...2011 4. TITLE AND SUBTITLE A WEAKEST-LINK APPROACH FOR FATIGUE LIMIT OF 30CrNiMo8 STEELS (PREPRINT) 5a. CONTRACT NUMBER In-house 5b. GRANT

  5. 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.

  6. A Novel Topology Link-Controlling Approach for Active Defense of a Node in a Network

    Directory of Open Access Journals (Sweden)

    Jun Li

    2017-03-01

    Full Text Available With the rapid development of virtual machine technology and cloud computing, distributed denial of service (DDoS attacks, or some peak traffic, poses a great threat to the security of the network. In this paper, a novel topology link control technique and mitigation attacks in real-time environments is proposed. Firstly, a non-invasive method of deploying virtual sensors in the nodes is built, which uses the resource manager of each monitored node as a sensor. Secondly, a general topology-controlling approach of resisting the tolerant invasion is proposed. In the proposed approach, a prediction model is constructed by using copula functions for predicting the peak of a resource through another resource. The result of prediction determines whether or not to initiate the active defense. Finally, a minority game with incomplete strategy is employed to suppress attack flows and improve the permeability of the normal flows. The simulation results show that the proposed approach is very effective in protecting nodes.

  7. 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...

  8. Opening Up Climate Research: A Linked Data Approach to Publishing Data Provenance

    Directory of Open Access Journals (Sweden)

    Arif Shaon

    2012-03-01

    Full Text Available Traditionally, the formal scientific output in most fields of natural science has been limited to peer-reviewed academic journal publications, with less attention paid to the chain of intermediate data results and their associated metadata, including provenance. In effect, this has constrained the representation and verification of the data provenance to the confines of the related publications. Detailed knowledge of a dataset’s provenance is essential to establish the pedigree of the data for its effective re-use, and to avoid redundant re-enactment of the experiment or computation involved. It is increasingly important for open-access data to determine their authenticity and quality, especially considering the growing volumes of datasets appearing in the public domain. To address these issues, we present an approach that combines the Digital Object Identifier (DOI – a widely adopted citation technique – with existing, widely adopted climate science data standards to formally publish detailed provenance of a climate research dataset as an associated scientific workflow. This is integrated with linked-data compliant data re-use standards (e.g. OAI-ORE to enable a seamless link between a publication and the complete trail of lineage of the corresponding dataset, including the dataset itself.

  9. Linking microbial and ecosystem ecology using ecological stoichiometry: a synthesis of conceptual and empirical approaches

    Science.gov (United States)

    Hall, E.K.; Maixner, F.; Franklin, O.; Daims, H.; Richter, A.; Battin, T.

    2011-01-01

    Currently, one of the biggest challenges in microbial and ecosystem ecology is to develop conceptual models that organize the growing body of information on environmental microbiology into a clear mechanistic framework with a direct link to ecosystem processes. Doing so will enable development of testable hypotheses to better direct future research and increase understanding of key constraints on biogeochemical networks. Although the understanding of phenotypic and genotypic diversity of microorganisms in the environment is rapidly accumulating, how controls on microbial physiology ultimately affect biogeochemical fluxes remains poorly understood. We propose that insight into constraints on biogeochemical cycles can be achieved by a more rigorous evaluation of microbial community biomass composition within the context of ecological stoichiometry. Multiple recent studies have pointed to microbial biomass stoichiometry as an important determinant of when microorganisms retain or recycle mineral nutrients. We identify the relevant cellular components that most likely drive changes in microbial biomass stoichiometry by defining a conceptual model rooted in ecological stoichiometry. More importantly, we show how X-ray microanalysis (XRMA), nanoscale secondary ion mass spectroscopy (NanoSIMS), Raman microspectroscopy, and in situ hybridization techniques (for example, FISH) can be applied in concert to allow for direct empirical evaluation of the proposed conceptual framework. This approach links an important piece of the ecological literature, ecological stoichiometry, with the molecular front of the microbial revolution, in an attempt to provide new insight into how microbial physiology could constrain ecosystem processes.

  10. Combinatorial Approach for the Discovery of New Scintillating Materials SBIR Phase I Final Report DOE/ER/84310

    International Nuclear Information System (INIS)

    Cronin, J.P.; Agrawal, A.; Tonazzi, J.C.

    2006-01-01

    The combinatorial approach for the discovery of new scintillating materials has been investigated using the wet-chemical (sol-gel) synthesis methods. Known scintillating compounds Lu 2 SiO 5 (LSO) and (LuAl)O 3 (LAO) and solid solutions in the systems of Lu 2 O 3 -Y 2 O 3 --SiO 2 (CeO 2 -doped) (LYSO) and Lu 2 O 3 -Y 2 O 3 --Al 2 O 3 (CeO 2 -doped) (LYAO) were synthesized from sol-gel precursors. Sol-gel precursors were formulated from alkoxides and nitrates and acetates of the cations. Sol-gel solution precursors were formulated for the printing of microdot arrays of different compositions in the above oxide systems. Microdot arrays were successfully printed on C-cut and R-cut sapphire substrates using Biodot printer at Los Alamos National Laboratory (LANL). The microdot arrays were adherent and stable after heat-treating at 1665 C and had an average thickness of around 2 (micro)m. X-ray fluorescence elemental mapping showed the arrays to be of the correct chemical composition. Sintered microdots were found to be highly crystalline by microscopic observation and X-ray diffraction. Scintillation was not clearly detectable by visual observation under UV illumination and by video observation under the scanning electron beam of an SEM. The microdots were either poorly scintillating or not scintillating under the present synthesis and testing conditions. Further improvements in the synthesis and processing of the microdot arrays as well as extensive scintillation testing are needed

  11. 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....

  12. A semantic-based approach for querying linked data using natural language

    KAUST Repository

    Paredes-Valverde, Mario Andrés

    2016-01-11

    The semantic Web aims to provide to Web information with a well-defined meaning and make it understandable not only by humans but also by computers, thus allowing the automation, integration and reuse of high-quality information across different applications. However, current information retrieval mechanisms for semantic knowledge bases are intended to be only used by expert users. In this work, we propose a natural language interface that allows non-expert users the access to this kind of information through formulating queries in natural language. The present approach uses a domain-independent ontology model to represent the question\\'s structure and context. Also, this model allows determination of the answer type expected by the user based on a proposed question classification. To prove the effectiveness of our approach, we have conducted an evaluation in the music domain using LinkedBrainz, an effort to provide the MusicBrainz information as structured data on the Web by means of Semantic Web technologies. Our proposal obtained encouraging results based on the F-measure metric, ranging from 0.74 to 0.82 for a corpus of questions generated by a group of real-world end users. © The Author(s) 2015.

  13. A semantic-based approach for querying linked data using natural language

    KAUST Repository

    Paredes-Valverde, Mario André s; Valencia-Garcí a, Rafael; Rodriguez-Garcia, Miguel Angel; Colomo-Palacios, Ricardo; Alor-Herná ndez, Giner

    2016-01-01

    The semantic Web aims to provide to Web information with a well-defined meaning and make it understandable not only by humans but also by computers, thus allowing the automation, integration and reuse of high-quality information across different applications. However, current information retrieval mechanisms for semantic knowledge bases are intended to be only used by expert users. In this work, we propose a natural language interface that allows non-expert users the access to this kind of information through formulating queries in natural language. The present approach uses a domain-independent ontology model to represent the question's structure and context. Also, this model allows determination of the answer type expected by the user based on a proposed question classification. To prove the effectiveness of our approach, we have conducted an evaluation in the music domain using LinkedBrainz, an effort to provide the MusicBrainz information as structured data on the Web by means of Semantic Web technologies. Our proposal obtained encouraging results based on the F-measure metric, ranging from 0.74 to 0.82 for a corpus of questions generated by a group of real-world end users. © The Author(s) 2015.

  14. Linking geodiversity and biodiversity in protected area management: developing a more integrated approach

    Science.gov (United States)

    Gordon, John

    2014-05-01

    The ecosystem approach is now a key driver for conservation policy globally. By definition an ecosystem includes both abiotic and biotic components interacting as a functional unit. However, the role of geodiversity generally remains poorly recognised both at a policy level and in the practical management of protected areas. This presentation examines key links between geodiversity and biodiversity, and demonstrates the benefits of better integration both to enhance conservation of geoheritage and the role of geodiversity in ecosystem management. Geodiversity contributes essentially to most of the ecosystem services recognised in the Millennium Ecosystem Assessment. It underpins biodiversity from micro- to macro-scales through the influence of factors such as lithology, topography, sediments, soils and hydrology. Most habitats and species depend on the abiotic 'stage' on which they exist. Active geological processes also help to determine the heterogeneity of the physical environment, creating mosaics of landforms, surface deposits and dynamic environments that support a range of biodiversity. In the face of climate change and other human pressures, maintaining and enhancing geodiversity should help to 'future-proof' biodiversity in the longer term. Learning from the past through palaeoenvironmental records can also enable better understanding of ecosystem dynamics. As well as recognising the value of geoheritage in its own right, a more integrated approach to conservation in protected areas would benefit both biodiversity and geodiversity, incorporating the concept of 'conserving the stage' (Anderson & Ferree, 2010) and the maintenance of natural processes. As part of developing the scientific framework of geodiversity, this requires geoscience engagement in the ecosystem approach, including evidence-based interdisciplinary research on the functional links between geodiversity and biodiversity across a range of spatial and temporal scales both to inform policy and

  15. Linking biogeomorphic feedbacks from ecosystem engineer to landscape scale: a panarchy approach

    Science.gov (United States)

    Eichel, Jana

    2017-04-01

    Scale is a fundamental concept in both ecology and geomorphology. Therefore, scale-based approaches are a valuable tool to bridge the disciplines and improve the understanding of feedbacks between geomorphic processes, landforms, material and organisms and ecological processes in biogeomorphology. Yet, linkages between biogeomorphic feedbacks on different scales, e.g. between ecosystem engineering and landscape scale patterns and dynamics, are not well understood. A panarchy approach sensu Holling et al. (2002) can help to close this research gap and explain how structure and function are created in biogeomorphic ecosystems. Based on results from previous biogeomorphic research in Turtmann glacier foreland (Switzerland; Eichel, 2017; Eichel et al. 2013, 2016), a panarchy concept is presented for lateral moraine slope biogeomorphic ecosystems. It depicts biogeomorphic feedbacks on different spatiotemporal scales as a set of nested adaptive cycles and links them by 'remember' and 'revolt' connections. On a small scale (cm2 - m2; seconds to years), the life cycle of the ecosystem engineer Dryas octopetala L. is considered as an adaptive cycle. Biogeomorphic succession within patches created by geomorphic processes represents an intermediate scale adaptive cycle (m2 - ha, years to decades), while geomorphic and ecologic pattern development at a landscape scale (ha - km2, decades to centuries) can be illustrated by an adaptive cycle of ‚biogeomorphic patch dynamics' (Eichel, 2017). In the panarchy, revolt connections link the smaller scale adaptive cycles to larger scale cycles: on lateral moraine slopes, the development of ecosystem engineer biomass and cover controls the engineering threshold of the biogeomorphic feedback window (Eichel et al., 2016) and therefore the onset of the biogeomorphic phase during biogeomorphic succession. In this phase, engineer patches and biogeomorphic structures can be created in the patch mosaic of the landscape. Remember connections

  16. A feature-based approach for best arm identification in the case of the Monte Carlo search algorithm discovery for one-player games

    OpenAIRE

    Taralla, David

    2013-01-01

    The field of reinforcement learning recently received the contribution by Ernst et al. (2013) "Monte carlo search algorithm discovery for one player games" who introduced a new way to conceive completely new algorithms. Moreover, it brought an automatic method to find the best algorithm to use in a particular situation using a multi-arm bandit approach. We address here the problem of best arm identification. The main problem is that the generated algorithm space (ie. the arm space) can be qui...

  17. Functional Enzyme-Based Approach for Linking Microbial Community Functions with Biogeochemical Process Kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Li, Minjing [School; Qian, Wei-jun [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; Gao, Yuqian [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; Shi, Liang [School; Liu, Chongxuan [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; School

    2017-09-28

    The kinetics of biogeochemical processes in natural and engineered environmental systems are typically described using Monod-type or modified Monod-type models. These models rely on biomass as surrogates for functional enzymes in microbial community that catalyze biogeochemical reactions. A major challenge to apply such models is the difficulty to quantitatively measure functional biomass for constraining and validating the models. On the other hand, omics-based approaches have been increasingly used to characterize microbial community structure, functions, and metabolites. Here we proposed an enzyme-based model that can incorporate omics-data to link microbial community functions with biogeochemical process kinetics. The model treats enzymes as time-variable catalysts for biogeochemical reactions and applies biogeochemical reaction network to incorporate intermediate metabolites. The sequences of genes and proteins from metagenomes, as well as those from the UniProt database, were used for targeted enzyme quantification and to provide insights into the dynamic linkage among functional genes, enzymes, and metabolites that are necessary to be incorporated in the model. The application of the model was demonstrated using denitrification as an example by comparing model-simulated with measured functional enzymes, genes, denitrification substrates and intermediates

  18. From Field to Laboratory: A New Database Approach for Linking Microbial Field Ecology with Laboratory Studies

    Science.gov (United States)

    Bebout, Leslie; Keller, R.; Miller, S.; Jahnke, L.; DeVincenzi, D. (Technical Monitor)

    2002-01-01

    The Ames Exobiology Culture Collection Database (AECC-DB) has been developed as a collaboration between microbial ecologists and information technology specialists. It allows for extensive web-based archiving of information regarding field samples to document microbial co-habitation of specific ecosystem micro-environments. Documentation and archiving continues as pure cultures are isolated, metabolic properties determined, and DNA extracted and sequenced. In this way metabolic properties and molecular sequences are clearly linked back to specific isolates and the location of those microbes in the ecosystem of origin. Use of this database system presents a significant advancement over traditional bookkeeping wherein there is generally little or no information regarding the environments from which microorganisms were isolated. Generally there is only a general ecosystem designation (i.e., hot-spring). However within each of these there are a myriad of microenvironments with very different properties and determining exactly where (which microenvironment) a given microbe comes from is critical in designing appropriate isolation media and interpreting physiological properties. We are currently using the database to aid in the isolation of a large number of cyanobacterial species and will present results by PI's and students demonstrating the utility of this new approach.

  19. Discovery expedition as an educational approach to improve the effectiveness of Master’s training for modern RF industry

    Directory of Open Access Journals (Sweden)

    Boiarova Elena

    2016-01-01

    Full Text Available The questions of improving educational technologies of highly qualified personnel training in Russia that takes into account all stakeholders are considered. The effective educational method of training at HSSE MIPT – Discovery expedition – is presented. Advantages of DE and its influence on science-intensive competences formation and increase of master’s training effectiveness are analyzed.

  20. On the plausibility of socioeconomic mortality estimates derived from linked data: a demographic approach.

    Science.gov (United States)

    Lerch, Mathias; Spoerri, Adrian; Jasilionis, Domantas; Viciana Fernandèz, Francisco

    2017-07-14

    Reliable estimates of mortality according to socioeconomic status play a crucial role in informing the policy debate about social inequality, social cohesion, and exclusion as well as about the reform of pension systems. Linked mortality data have become a gold standard for monitoring socioeconomic differentials in survival. Several approaches have been proposed to assess the quality of the linkage, in order to avoid the misclassification of deaths according to socioeconomic status. However, the plausibility of mortality estimates has never been scrutinized from a demographic perspective, and the potential problems with the quality of the data on the at-risk populations have been overlooked. Using indirect demographic estimation (i.e., the synthetic extinct generation method), we analyze the plausibility of old-age mortality estimates according to educational attainment in four European data contexts with different quality issues: deterministic and probabilistic linkage of deaths, as well as differences in the methodology of the collection of educational data. We evaluate whether the at-risk population according to educational attainment is misclassified and/or misestimated, correct these biases, and estimate the education-specific linkage rates of deaths. The results confirm a good linkage of death records within different educational strata, even when probabilistic matching is used. The main biases in mortality estimates concern the classification and estimation of the person-years of exposure according to educational attainment. Changes in the census questions about educational attainment led to inconsistent information over time, which misclassified the at-risk population. Sample censuses also misestimated the at-risk populations according to educational attainment. The synthetic extinct generation method can be recommended for quality assessments of linked data because it is capable not only of quantifying linkage precision, but also of tracking problems in

  1. 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...

  2. 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)

  3. Linking 1D coastal ocean modelling to environmental management: an ensemble approach

    Science.gov (United States)

    Mussap, Giulia; Zavatarelli, Marco; Pinardi, Nadia

    2017-12-01

    The use of a one-dimensional interdisciplinary numerical model of the coastal ocean as a tool contributing to the formulation of ecosystem-based management (EBM) is explored. The focus is on the definition of an experimental design based on ensemble simulations, integrating variability linked to scenarios (characterised by changes in the system forcing) and to the concurrent variation of selected, and poorly constrained, model parameters. The modelling system used was previously specifically designed for the use in "data-rich" areas, so that horizontal dynamics can be resolved by a diagnostic approach and external inputs can be parameterised by nudging schemes properly calibrated. Ensembles determined by changes in the simulated environmental (physical and biogeochemical) dynamics, under joint forcing and parameterisation variations, highlight the uncertainties associated to the application of specific scenarios that are relevant to EBM, providing an assessment of the reliability of the predicted changes. The work has been carried out by implementing the coupled modelling system BFM-POM1D in an area of Gulf of Trieste (northern Adriatic Sea), considered homogeneous from the point of view of hydrological properties, and forcing it by changing climatic (warming) and anthropogenic (reduction of the land-based nutrient input) pressure. Model parameters affected by considerable uncertainties (due to the lack of relevant observations) were varied jointly with the scenarios of change. The resulting large set of ensemble simulations provided a general estimation of the model uncertainties related to the joint variation of pressures and model parameters. The information of the model result variability aimed at conveying efficiently and comprehensibly the information on the uncertainties/reliability of the model results to non-technical EBM planners and stakeholders, in order to have the model-based information effectively contributing to EBM.

  4. Linking genes to microbial growth kinetics: an integrated biochemical systems engineering approach.

    Science.gov (United States)

    Koutinas, Michalis; Kiparissides, Alexandros; Silva-Rocha, Rafael; Lam, Ming-Chi; Martins Dos Santos, Vitor A P; de Lorenzo, Victor; Pistikopoulos, Efstratios N; Mantalaris, Athanasios

    2011-07-01

    The majority of models describing the kinetic properties of a microorganism for a given substrate are unstructured and empirical. They are formulated in this manner so that the complex mechanism of cell growth is simplified. Herein, a novel approach for modelling microbial growth kinetics is proposed, linking biomass growth and substrate consumption rates to the gene regulatory programmes that control these processes. A dynamic model of the TOL (pWW0) plasmid of Pseudomonas putida mt-2 has been developed, describing the molecular interactions that lead to the transcription of the upper and meta operons, known to produce the enzymes for the oxidative catabolism of m-xylene. The genetic circuit model was combined with a growth kinetic model decoupling biomass growth and substrate consumption rates, which are expressed as independent functions of the rate-limiting enzymes produced by the operons. Estimation of model parameters and validation of the model's predictive capability were successfully performed in batch cultures of mt-2 fed with different concentrations of m-xylene, as confirmed by relative mRNA concentration measurements of the promoters encoded in TOL. The growth formation and substrate utilisation patterns could not be accurately described by traditional Monod-type models for a wide range of conditions, demonstrating the critical importance of gene regulation for the development of advanced models closely predicting complex bioprocesses. In contrast, the proposed strategy, which utilises quantitative information pertaining to upstream molecular events that control the production of rate-limiting enzymes, predicts the catabolism of a substrate and biomass formation and could be of central importance for the design of optimal bioprocesses. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-10

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

  6. Easy and difficult performance-approach goals : Their moderating effect on the link between task interest and performance attainment

    NARCIS (Netherlands)

    Blaga, Monica; Van Yperen, N.W.

    2008-01-01

    The purpose of this study was to demonstrate that the positive link between task interest and performance attainment can he negatively affected by the pursuit of difficult performance-approach goals. This was tested in a sample of 60 undergraduate Students at a Dutch university, In line with

  7. 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.

  8. A marketing-finance approach linking contracts in agricultural channels to shareholder value

    NARCIS (Netherlands)

    Pennings, J.M.E.; Wansink, B.; Hoffmann, A.O.I.

    2011-01-01

    A conceptual marketing-finance framework is proposed which links channel contracting in agriculture and the use of financial facilitating services (e.g., financial derivatives) to (shareholder) value creation. The framework complements existing literature by explicitly including channel contract

  9. 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...

  10. A MODIFIED ROUTE DISCOVERY APPROACH FOR DYNAMIC SOURCE ROUTING (DSR PROTOCOL IN MOBILE AD-HOC NETWORKS

    Directory of Open Access Journals (Sweden)

    Alaa Azmi Allahham

    2017-02-01

    Full Text Available Mobile Ad-hoc networks (MANETs involved in many applications, whether commercial or military because of their characteristics that do not depend on the infrastructure as well as the freedom movement of their elements, but in return has caused this random mobility of the nodes many of the challenges, where the routing is considered one of these challenges. There are many types of routing protocols that operate within MANET networks, which responsible for finding paths between the source and destination nodes with the modernization of these paths which are constantly changing due to the dynamic topology of the network stemming from the constant random movement of the nodes. The DSR (Dynamic Source Routing routing protocol algorithm is one of these routing protocols which consist of two main stages; route discovery and maintenance, where the route discovery algorithm operates based on blind flooding of request messages. blind flooding is considered as the most well known broadcasting mechanism, it is inefficient in terms of communication and resource utilization, which causing increasing the probability of collisions, repeating send several copies of the same message, as well as increasing the delay. Hence, a new mechanism in route discovery stage and in caching the routes in DSR algorithm according to the node's location in the network and the direction of the broadcast is proposed for better performance especially in terms of delay as well as redundant packets rate. The implementation of proposed algorithms showed positive results in terms of delay, overhead, and improve the performance of MANETs in general.

  11. Operative Links

    DEFF Research Database (Denmark)

    Wistoft, Karen; Højlund, Holger

    2012-01-01

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

  12. Enzymatic cross-linking of human recombinant elastin (HELP) as biomimetic approach in vascular tissue engineering.

    Science.gov (United States)

    Bozzini, Sabrina; Giuliano, Liliana; Altomare, Lina; Petrini, Paola; Bandiera, Antonella; Conconi, Maria Teresa; Farè, Silvia; Tanzi, Maria Cristina

    2011-12-01

    The use of polymers naturally occurring in the extracellular matrix (ECM) is a promising strategy in regenerative medicine. If compared to natural ECM proteins, proteins obtained by recombinant DNA technology have intrinsic advantages including reproducible macromolecular composition, sequence and molecular mass, and overcoming the potential pathogens transmission related to polymers of animal origin. Among ECM-mimicking materials, the family of recombinant elastin-like polymers is proposed for drug delivery applications and for the repair of damaged elastic tissues. This work aims to evaluate the potentiality of a recombinant human elastin-like polypeptide (HELP) as a base material of cross-linked matrices for regenerative medicine. The cross-linking of HELP was accomplished by the insertion of cross-linking sites, glutamine and lysine, in the recombinant polymer and generating ε-(γ-glutamyl) lysine links through the enzyme transglutaminase. The cross-linking efficacy was estimated by infrared spectroscopy. Freeze-dried cross-linked matrices showed swelling ratios in deionized water (≈2500%) with good structural stability up to 24 h. Mechanical compression tests, performed at 37°C in wet conditions, in a frequency sweep mode, indicated a storage modulus of 2/3 kPa, with no significant changes when increasing number of cycles or frequency. These results demonstrate the possibility to obtain mechanically resistant hydrogels via enzymatic crosslinking of HELP. Cytotoxicity tests of cross-linked HELP were performed with human umbilical vein endothelial cells, by use of transwell filter chambers for 1-7 days, or with its extracts in the opportune culture medium for 24 h. In both cases no cytotoxic effects were observed in comparison with the control cultures. On the whole, the results suggest the potentiality of this genetically engineered HELP for regenerative medicine applications, particularly for vascular tissue regeneration.

  13. QBCov: A Linked Data interface for Discrete Global Grid Systems, a new approach to delivering coverage data on the web

    Science.gov (United States)

    Zhang, Z.; Toyer, S.; Brizhinev, D.; Ledger, M.; Taylor, K.; Purss, M. B. J.

    2016-12-01

    We are witnessing a rapid proliferation of geoscientific and geospatial data from an increasing variety of sensors and sensor networks. This data presents great opportunities to resolve cross-disciplinary problems. However, working with it often requires an understanding of file formats and protocols seldom used outside of scientific computing, potentially limiting the data's value to other disciplines. In this paper, we present a new approach to serving satellite coverage data on the web, which improves ease-of-access using the principles of linked data. Linked data adapts the concepts and protocols of the human-readable web to machine-readable data; the number of developers familiar with web technologies makes linked data a natural choice for bringing coverages to a wider audience. Our approach to using linked data also makes it possible to efficiently service high-level SPARQL queries: for example, "Retrieve all Landsat ETM+ observations of San Francisco between July and August 2016" can easily be encoded in a single query. We validate the new approach, which we call QBCov, with a reference implementation of the entire stack, including a simple web-based client for interacting with Landsat observations. In addition to demonstrating the utility of linked data for publishing coverages, we investigate the heretofore unexplored relationship between Discrete Global Grid Systems (DGGS) and linked data. Our conclusions are informed by the aforementioned reference implementation of QBCov, which is backed by a hierarchical file format designed around the rHEALPix DGGS. Not only does the choice of a DGGS-based representation provide an efficient mechanism for accessing large coverages at multiple scales, but the ability of DGGS to produce persistent, unique identifiers for spatial regions is especially valuable in a linked data context. This suggests that DGGS has an important role to play in creating sustainable and scalable linked data infrastructures. QBCov is being

  14. An Integrated Approach for Reliable Facility Location/Network Design Problem with Link Disruption

    Directory of Open Access Journals (Sweden)

    Davood Shishebori

    2015-05-01

    Full Text Available Proposing a robust designed facility location is one of the most effective ways to hedge against unexpected disruptions and failures in a transportation network system. This paper considers the combined facility location/network design problem with regard to transportation link disruptions and develops a mixed integer linear programming formulation to model it. With respect to the probability of link disruptions, the objective function of the model minimizes the total costs, including location costs, link construction costs and also the expected transportation costs. An efficient hybrid algorithm based on LP relaxation and variable neighbourhood search metaheuristic is developed in order to solve the mathematical model. Numerical results demonstrate that the proposed hybrid algorithm has suitable efficiency in terms of duration of solution time and determining excellent solution quality.

  15. Fighting obesity with a sugar-based library: discovery of novel MCH-1R antagonists by a new computational-VAST approach for exploration of GPCR binding sites.

    Science.gov (United States)

    Heifetz, Alexander; Barker, Oliver; Verquin, Geraldine; Wimmer, Norbert; Meutermans, Wim; Pal, Sandeep; Law, Richard J; Whittaker, Mark

    2013-05-24

    Obesity is an increasingly common disease. While antagonism of the melanin-concentrating hormone-1 receptor (MCH-1R) has been widely reported as a promising therapeutic avenue for obesity treatment, no MCH-1R antagonists have reached the market. Discovery and optimization of new chemical matter targeting MCH-1R is hindered by reduced HTS success rates and a lack of structural information about the MCH-1R binding site. X-ray crystallography and NMR, the major experimental sources of structural information, are very slow processes for membrane proteins and are not currently feasible for every GPCR or GPCR-ligand complex. This situation significantly limits the ability of these methods to impact the drug discovery process for GPCR targets in "real-time", and hence, there is an urgent need for other practical and cost-efficient alternatives. We present here a conceptually pioneering approach that integrates GPCR modeling with design, synthesis, and screening of a diverse library of sugar-based compounds from the VAST technology (versatile assembly on stable templates) to provide structural insights on the MCH-1R binding site. This approach creates a cost-efficient new avenue for structure-based drug discovery (SBDD) against GPCR targets. In our work, a primary VAST hit was used to construct a high-quality MCH-1R model. Following model validation, a structure-based virtual screen yielded a 14% hit rate and 10 novel chemotypes of potent MCH-1R antagonists, including EOAI3367472 (IC50 = 131 nM) and EOAI3367474 (IC50 = 213 nM).

  16. In search of new lead compounds for trypanosomiasis drug design: A protein structure-based linked-fragment approach

    Science.gov (United States)

    Verlinde, Christophe L. M. J.; Rudenko, Gabrielle; Hol, Wim G. J.

    1992-04-01

    A modular method for pursuing structure-based inhibitor design in the framework of a design cycle is presented. The approach entails four stages: (1) a design pathway is defined in the three-dimensional structure of a target protein; (2) this pathway is divided into subregions; (3) complementary building blocks, also called fragments, are designed in each subregion; complementarity is defined in terms of shape, hydrophobicity, hydrogen bond properties and electrostatics; and (4) fragments from different subregions are linked into potential lead compounds. Stages (3) and (4) are qualitatively guided by force-field calculations. In addition, the designed fragments serve as entries for retrieving existing compounds from chemical databases. This linked-fragment approach has been applied in the design of potentially selective inhibitors of triosephosphate isomerase from Trypanosoma brucei, the causative agent of sleeping sickness.

  17. 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

  18. A Methodological Alternative to Media Comparison Studies: Linking Information Utilization Strategies and Instructional Approach in Hypermedia Learning

    OpenAIRE

    Catrambone, Richard; Gerjets, Peter; Scheiter, Katharina; Vollmann, Brigitte

    2006-01-01

    Literature reviews on hypermedia learning have yet failed to show consistent positive effects of learner-controlled nonlinear information access. We argue that a possible reason for this lack of evidence in favor of hypermedia learning results from the fact that not sufficient attention is paid to the strategies of information utilization learners deploy. The few studies that do analyze these strategies fail to link them to an instructional approach, which hampers a deeper interpretation of s...

  19. Linking Economic Value Added, Direct Costing, and the Lean Thinking to the Balanced Scorecard in a System Dynamics Modelling Approach

    DEFF Research Database (Denmark)

    Nielsen, Steen; Nielsen, Erland Hejn

    Review, July-August, 2007], provide evidence that companies fail to see the possible benefits of combining and integrating several accounting practices into a single framework. Design/methodology/approach - We use a System Dynamics Modelling approach to the BSC-thinking. The BSC model includes the five...... Purpose - To show how three practices normally applied separately can be linked to support the strategy evaluation and the performance measurement in the balanced scorecard. Recent studies, e.g. Kaplan and Norton [Using the Balanced Scorecard as a Strategic Management System, Harvard Business...

  20. Childhood maltreatment and its link to borderline personality disorder features in children: A systematic review approach.

    Science.gov (United States)

    Ibrahim, Jeyda; Cosgrave, Nicola; Woolgar, Matthew

    2018-01-01

    Borderline personality disorder has repeatedly been associated with a history of maltreatment in childhood; however, research on maltreatment and its link to borderline features in children is limited. The aim of this review is to synthesise the existing data on the association between maltreatment and borderline features in childhood. In total, 10 studies were included in this systematic review. Studies indicated that children with borderline features were more likely to have a history of maltreatment, and that children who had been maltreated were more likely to present with borderline features. Other risk factors such as cognitive and executive functioning deficits, parental dysfunction and genetic vulnerability were also identified across studies. This review adds to the literature by highlighting maltreatment as a risk factor for borderline features in childhood. Longitudinal research is required to establish the link between childhood borderline features and adult borderline features. Implications for early identification, prevention and intervention services are discussed.

  1. Phylogeny-guided (meta)genome mining approach for the targeted discovery of new microbial natural products.

    Science.gov (United States)

    Kang, Hahk-Soo

    2017-02-01

    Genomics-based methods are now commonplace in natural products research. A phylogeny-guided mining approach provides a means to quickly screen a large number of microbial genomes or metagenomes in search of new biosynthetic gene clusters of interest. In this approach, biosynthetic genes serve as molecular markers, and phylogenetic trees built with known and unknown marker gene sequences are used to quickly prioritize biosynthetic gene clusters for their metabolites characterization. An increase in the use of this approach has been observed for the last couple of years along with the emergence of low cost sequencing technologies. The aim of this review is to discuss the basic concept of a phylogeny-guided mining approach, and also to provide examples in which this approach was successfully applied to discover new natural products from microbial genomes and metagenomes. I believe that the phylogeny-guided mining approach will continue to play an important role in genomics-based natural products research.

  2. Determinants Linked to Family Business Sustainability in the UAE: An AHP Approach

    OpenAIRE

    Mohammed Oudah; Fauzia Jabeen; Christopher Dixon

    2018-01-01

    The purpose of this study is to identify and prioritise the various success factors linked to the sustainability of large and medium sized family businesses (FB) in the United Arab Emirates (UAE). A well-researched methodology was used for the synthesis of priorities and the measurement of consistencies. The analytic hierarchy process (AHP) model was developed with seven criteria and 15 sub-criteria gleaned from prior research. Data were collected using an interview-based survey conducted on ...

  3. Valuing Manggarai Station – Soekarno-Hatta International Airport Rail Link Using Stated Preference Approach

    OpenAIRE

    Adi, Wahyu Tamtomo

    2015-01-01

    This study attempts to identify the characteristics and preference of the SHIA airport travelers, estimate the subjective value of in-vehicle time and waiting time by providing choice experiments regarding the available modes in combination with the Airport Rail Link (ARL) service as hypothetical situation, analyze how the values vary according to the socio-demographics of respondents and forecasting the mode sharing and the elasticity based on several scenarios. Five hundred respondents as p...

  4. Linking the effects of land use change with water quality and discharge :an integrated approach

    OpenAIRE

    Fauss, Lynn Michael

    1992-01-01

    Hydrologic and water-quality equilibria are greatly affected by changing land use. This study presents a methodology that integrates the use of remote sensing, geographical information systems (GIS) and water-quality modeling. Archived aerial photography proved to be a valuable source of historical land use data. GIS technology was used to compile and analyze spatial data. A comprehensive watershed model was used to link the effects of land use change to water quali...

  5. 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

  6. Missing links between lean startup, design thinking, and experiential learning approaches in entrepreneurship education

    DEFF Research Database (Denmark)

    Ramsgaard, Michael Breum; Christensen, Marie Ernst

    2016-01-01

    Questions we care about • How do different pedagogical teaching approaches in entrepreneurship education construct learning outcome when comparing the underlying pedagogical models? • Where can unidentified fields and correlations of pedagogical insights between the approaches of lean startup......, design thinking, and experiential learning be identified? • How can new concepts of learning models, taking lean startup, design thinking and experiential learning approaches into account, be developed in entrepreneurship education? Approach This 3e conference paper begins as a conceptual paper...... highlighting the theories and underlying learning models behind three pedagogical approaches within entrepreneurship education, namely lean startup, design thinking and experiential learning. The paper builds this knowledge framework in order to set the design for an empirical investigation of the proposed...

  7. Systems biological approach to investigate the lack of familial link between Down's Syndrome & Neural Tube Disorders.

    Science.gov (United States)

    Ragunath, Pk; Abhinand, Pa

    2013-01-01

    Systems Biology involves the study of the interactions of biological systems and ultimately their functions. Down's syndrome (DS) is one of the most common genetic disorders which are caused by complete, or occasionally partial, triplication of chromosome 21, characterized by cognitive and language dysfunction coupled with sensory and neuromotor deficits. Neural Tube Disorders (NTDs) are a group of congenital malformations of the central nervous system and neighboring structures related to defective neural tube closure during the first trimester of pregnancy usually occurring between days 18-29 of gestation. Several studies in the past have provided considerable evidence that abnormal folate and methyl metabolism are associated with onset of DS & NTDs. There is a possible common etiological pathway for both NTDs and Down's syndrome. But, various research studies over the years have indicated very little evidence for familial link between the two disorders. Our research aimed at the gene expression profiling of microarray datasets pertaining to the two disorders to identify genes whose expression levels are significantly altered in these conditions. The genes which were 1.5 fold unregulated and having a p-value disorders were recognized and over representation analysis was carried out for each of the constituent genes. The comprehensive manual analysis of these genes yields a hypothetical understanding of the lack of familial link between DS and NTDs. There were no genes involved with folic acid present in the dense cliques. Only - CBL, EGFR genes were commonly present, which makes the allelic variants of these genes - good candidates for future studies regarding the familial link between DS and NTDs. NTD - Neural Tube Disorders, DS - Down's Syndrome, MTHFR - Methylenetetrahydrofolate reductase, MTRR- 5 - methyltetrahydrofolate-homocysteine methyltransferase reductase.

  8. On the link between oil and commodity prices: a panel VAR approach

    International Nuclear Information System (INIS)

    Bremond, Vincent; Hache, Emmanuel; Joets, Marc

    2013-12-01

    The aim of this paper is to study the relationships between the price of oil and a large dataset of commodity prices, relying on panel data settings. Using second generation panel co-integration tests, our findings show that the WTI and commodity prices are not linked in the long term. Nevertheless, considering our results in causality tests, we show that short-run relations exist, mainly from the price of crude oil to commodity prices. We thus implement a panel VAR estimation with an impulse response function analysis. Two main conclusions emerge: (i) fast co-movements are highlighted, while (ii) market efficiency is emphasized. (authors)

  9. The non-linear link between electricity consumption and temperature in Europe: A threshold panel approach

    Energy Technology Data Exchange (ETDEWEB)

    Bessec, Marie [CGEMP, Universite Paris-Dauphine, Place du Marechal de Lattre de Tassigny Paris (France); Fouquau, Julien [LEO, Universite d' Orleans, Faculte de Droit, d' Economie et de Gestion, Rue de Blois, BP 6739, 45067 Orleans Cedex 2 (France)

    2008-09-15

    This paper investigates the relationship between electricity demand and temperature in the European Union. We address this issue by means of a panel threshold regression model on 15 European countries over the last two decades. Our results confirm the non-linearity of the link between electricity consumption and temperature found in more limited geographical areas in previous studies. By distinguishing between North and South countries, we also find that this non-linear pattern is more pronounced in the warm countries. Finally, rolling regressions show that the sensitivity of electricity consumption to temperature in summer has increased in the recent period. (author)

  10. Understanding Coastal Carbon Cycling by Linking Top-Down and Bottom-Up Approaches

    Science.gov (United States)

    Barr, Jordan G.; Troxler, Tiffany G.; Najjar, Raymond G.

    2014-09-01

    The coastal zone, despite occupying a small fraction of the Earth's surface area, is an important component of the global carbon (C) cycle. Coastal wetlands, including mangrove forests, tidal marshes, and seagrass meadows, compose a domain of large reservoirs of biomass and soil C [Fourqurean et al., 2012; Donato et al., 2011; Pendleton et al., 2012; Regnier et al., 2013; Bauer et al., 2013]. These wetlands and their associated C reservoirs (2 to 25 petagrams C; best estimate of 7 petagrams C [Pendleton et al., 2012]) provide numerous ecosystem services and serve as key links between land and ocean.

  11. Linking Individual Learning Styles to Approach-Avoidance Motivational Traits and Computational Aspects of Reinforcement Learning.

    Directory of Open Access Journals (Sweden)

    Kristoffer Carl Aberg

    Full Text Available Learning how to gain rewards (approach learning and avoid punishments (avoidance learning is fundamental for everyday life. While individual differences in approach and avoidance learning styles have been related to genetics and aging, the contribution of personality factors, such as traits, remains undetermined. Moreover, little is known about the computational mechanisms mediating differences in learning styles. Here, we used a probabilistic selection task with positive and negative feedbacks, in combination with computational modelling, to show that individuals displaying better approach (vs. avoidance learning scored higher on measures of approach (vs. avoidance trait motivation, but, paradoxically, also displayed reduced learning speed following positive (vs. negative outcomes. These data suggest that learning different types of information depend on associated reward values and internal motivational drives, possibly determined by personality traits.

  12. Linking Individual Learning Styles to Approach-Avoidance Motivational Traits and Computational Aspects of Reinforcement Learning

    Science.gov (United States)

    Carl Aberg, Kristoffer; Doell, Kimberly C.; Schwartz, Sophie

    2016-01-01

    Learning how to gain rewards (approach learning) and avoid punishments (avoidance learning) is fundamental for everyday life. While individual differences in approach and avoidance learning styles have been related to genetics and aging, the contribution of personality factors, such as traits, remains undetermined. Moreover, little is known about the computational mechanisms mediating differences in learning styles. Here, we used a probabilistic selection task with positive and negative feedbacks, in combination with computational modelling, to show that individuals displaying better approach (vs. avoidance) learning scored higher on measures of approach (vs. avoidance) trait motivation, but, paradoxically, also displayed reduced learning speed following positive (vs. negative) outcomes. These data suggest that learning different types of information depend on associated reward values and internal motivational drives, possibly determined by personality traits. PMID:27851807

  13. 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...

  14. A System-Wide Approach to Identify the Mechanisms of Barnacle Attachment: Toward the Discovery of New Antifouling Compounds

    KAUST Repository

    Al-Aqeel, Sarah

    2015-01-01

    , cuticle development, and eggshell formation, and down-regulation of genes in the nitric oxide pathway, which stimulates the swimming and feeding responses of marine invertebrates. This system-wide integrated approach elucidated the development

  15. Infection Control Link Nurse Program: An interdisciplinary approach n targeting health care-acquired infection

    Science.gov (United States)

    Sopirala, Madhuri M.; Yahle-Dunbar, Lisa; Smyer, Justin; Wellington, Linda; Dickman, Jeanne; Zikri, Nancy; Martin, Jennifer; Kulich, Pat; Taylor, David; Mekhjian, Hagop; Nash, Mary; Mansfield, Jerry; Pancholi, Preeti; Howard, Mary; Chase, Linda; Brown, Susan; Kipp, Kristopher; Lefeld, Kristen; Myers, Amber; Pan, Xueliang; Mangino, Julie E.

    2014-01-01

    Background We describe a successful interdisciplinary liaison program that effectively reduced health care-acquired (HCA), methicillin-resistant Staphylococcus aureus (MRSA) in a university hospital setting. Methods Baseline was from January 2006 to March 2008, and intervention period was April 2008 to September 2009. Staff nurses were trained to be liaisons (link nurses) to infection prevention (IP) personnel with clearly defined goals assigned and with ongoing monthly education. HCA-MRSA incidence per 1,000 patient-days (PD) was compared between baseline and intervention period along with total and non-HCA-MRSA, HCA and non-HCA-MRSA bacteremia, and hand soap/sanitizer usage. Hand hygiene compliance was assessed. Results A reduction in MRSA rates was as follows in intervention period compared with baseline: HCA-MRSA decreased by 28% from 0.92 to 0.67 cases per 1,000 PD (incidence rate ratio, 0.72; 95% confidence interval: 0.62–0.83, P Hand soap/sanitizer usage and compliance with hand hygiene also increased significantly during IP. Conclusion Link nurse program effectively reduced HCA-MRSA. Goal-defined metrics with ongoing reeducation for the nurses by IP personnel helped drive these results. PMID:24548456

  16. Introductory Geology From the Liberal Arts Approach: A Geology-Sociology Linked Course

    Science.gov (United States)

    Walsh, E. O.; Davis, E.

    2008-12-01

    Geology can be a hard sell to college students, especially to college students attending small, liberal arts institutions in localities that lack exaggerated topography. At these schools, Geology departments that wish to grow must work diligently to attract students to the major; professors must be able to convince a wider audience of students that geology is relevant to their everyday lives. Toward this end, a Physical Geology course was linked with an introductory Sociology course through the common theme of Consumption. The same students took the two courses in sequence, beginning with the Sociology course and ending with Physical Geology; thus, students began by discussing the role of consumption in society and ended by learning about the geological processes and implications of consumption. Students were able to ascertain the importance of geology in their daily lives by connecting Earth processes to specific products they consume, such as cell phones and bottled water. Students were also able to see the connection between seemingly disparate fields of study, which is a major goal of the liberal arts. As a theme, Consumption worked well to grab the attention of students interested in diverse issues, such as environmental science or social justice. A one-hour lecture illustrating the link between sociology and geology was developed for presentation to incoming freshmen and their parents to advertise the course. Initial response has been positive, showing an increase in awareness of geological processes among students with a wide range of interests.

  17. An Interactome-Centered Protein Discovery Approach Reveals Novel Components Involved in Mitosome Function and Homeostasis in Giardia lamblia.

    Directory of Open Access Journals (Sweden)

    Samuel Rout

    2016-12-01

    Full Text Available Protozoan parasites of the genus Giardia are highly prevalent globally, and infect a wide range of vertebrate hosts including humans, with proliferation and pathology restricted to the small intestine. This narrow ecological specialization entailed extensive structural and functional adaptations during host-parasite co-evolution. An example is the streamlined mitosomal proteome with iron-sulphur protein maturation as the only biochemical pathway clearly associated with this organelle. Here, we applied techniques in microscopy and protein biochemistry to investigate the mitosomal membrane proteome in association to mitosome homeostasis. Live cell imaging revealed a highly immobilized array of 30-40 physically distinct mitosome organelles in trophozoites. We provide direct evidence for the single giardial dynamin-related protein as a contributor to mitosomal morphogenesis and homeostasis. To overcome inherent limitations that have hitherto severely hampered the characterization of these unique organelles we applied a novel interaction-based proteome discovery strategy using forward and reverse protein co-immunoprecipitation. This allowed generation of organelle proteome data strictly in a protein-protein interaction context. We built an initial Tom40-centered outer membrane interactome by co-immunoprecipitation experiments, identifying small GTPases, factors with dual mitosome and endoplasmic reticulum (ER distribution, as well as novel matrix proteins. Through iterative expansion of this protein-protein interaction network, we were able to i significantly extend this interaction-based mitosomal proteome to include other membrane-associated proteins with possible roles in mitosome morphogenesis and connection to other subcellular compartments, and ii identify novel matrix proteins which may shed light on mitosome-associated metabolic functions other than Fe-S cluster biogenesis. Functional analysis also revealed conceptual conservation of protein

  18. Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

    International Nuclear Information System (INIS)

    Kumar, Bhowmik Salil; Lee, Young-Joo; Yi, Hong Jae; Chung, Bong Chul; Jung, Byung Hwa

    2010-01-01

    In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg -1 day -1 or 250 mg kg -1 day -1 for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

  19. Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Bhowmik Salil [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of); Lee, Young-Joo; Yi, Hong Jae [College of Pharmacy, Kyung Hee University, Hoegi-dong, Dongdaemun-gu, Seoul 130-791 (Korea, Republic of); Chung, Bong Chul [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); Jung, Byung Hwa, E-mail: jbhluck@kist.re.kr [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of)

    2010-02-19

    In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg{sup -1} day{sup -1} or 250 mg kg{sup -1} day{sup -1} for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

  20. The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders

    Directory of Open Access Journals (Sweden)

    Jocelien DA Olivier

    2013-06-01

    Full Text Available There is ample evidence that genetic factors play an important role in anxiety disorders. In support, human genome-wide association studies have implicated several novel candidate genes. However, illumination of such genetic factors involved in anxiety disorders has not resulted in novel drugs over the past decades. A complicating factor is the heterogeneous classification of anxiety disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR and diverging operationalization of anxiety used in preclinical and clinical studies. Currently, there is an increasing focus on the gene-environment interaction in anxiety as genes do not operate in isolation and environmental factors have been found to significantly contribute to the development of anxiety disorders in at-risk individuals. Nevertheless, extensive research on gene-environment mechanisms in anxiety has not resulted in major breakthroughs in drug discovery. Modification of individual genes in rodent models has enabled the specific study of anxiety in preclinical studies. In this context, two extensively studied neurotransmitters involved in anxiety are the GABA and 5-HT system. In this review, we illustrate the complex interplay between genes and environment in anxiety processes by reviewing preclinical and clinical studies on the serotonin transporter (5-HTT, 5-HT1A receptor, 5-HT2 receptor and GABAA receptor. Even though targets from the serotonin and GABA system have yielded drugs with known anxiolytic efficacy, the relation between the genetic background of these targets and anxiety symptoms and development of anxiety disorders is largely unknown. The aim of this review is to show the vast complexity of genetic and environmental factors in anxiety disorders. In light of the difficulty with which common genetic variants are identified in anxiety disorders, animal models with translational validity may aid in elucidating the neurobiological background of these genes

  1. Discovery of Bovine Digital Dermatitis-Associated Treponema spp. in the Dairy Herd Environment by a Targeted Deep-Sequencing Approach

    DEFF Research Database (Denmark)

    Schou, Kirstine Klitgaard; Weiss Nielsen, Martin; Ingerslev, Hans-Christian

    2014-01-01

    The bacteria associated with the infectious claw disease bovine digital dermatitis (DD) are spirochetes of the genus Treponema; however, their environmental reservoir remains unknown. To our knowledge, the current study is the first report of the discovery and phylogenetic characterization of r...... of this disease among cows within a herd as well as between herds. To address the issue of DD infection reservoirs, we searched for evidence of DD-associated treponemes in fresh feces, in slurry, and in hoof lesions by deep sequencing of the V3 and V4 hypervariable regions of the 16S rRNA gene coupled...... with identification at the operational-taxonomic-unit level. Using treponeme-specific primers in this high-throughput approach, we identified small amounts of DNA (on average 0.6% of the total amount of sequence reads) from DD-associated treponemes in 43 of 64 samples from slurry and cow feces collected from six...

  2. John Dewey’s theory of democracy and its links with the heterodox approach to economics.

    Directory of Open Access Journals (Sweden)

    Arturo Hermann

    2011-07-01

    Full Text Available John Dewey is one of the most significant figures in pragmatist philosophy, an approach which he systematically applied to the study of economic, social and cultural structure. In our work, we will focus on the main aspects of Dewey’s approach to the study of aspects that make up “human nature” and how do they interact with the characteristics of the cultural context. We will illustrate how the concepts elaborated by Dewey can contribute to the heterodox analysis of a host of economic and social issues. Dewey highlights the crucial role of public policies for facilitating the development of volunteer associations in all areas of the social structure. In the analysis of these aspects, Dewey’s key contribution lies in removing the concepts of democracy and participation from the limbo of abstraction in which they tended to be confined by previous approaches and connecting them to the evolution of economic and social forms.

  3. The Approach for Optimization of Transmission over Power Links using the Thyristor-Controlled Series Compensation

    Directory of Open Access Journals (Sweden)

    Fatima Zohra GHERBI

    2008-07-01

    Full Text Available The energy transportation networks can be improved by multiplying or creating new lines. This is not always the case for various reasons. The series capacities controlled by SCRs (Silicon Controlled Rectifiers represent a good alternative to optimize the existing or the new electric links, because they allow the increase of the dynamic stability, the damping of the power oscillations, while balancing the loads between the parallel circuits. This paper presents a resolution method to the power distribution by inserting the TCSC transit controller in the network. The insertion of the TCSC devices has given satisfying results that are, an increase of the transmitted active power and reduction of active losses, an improvement of the angular stability and the voltage stability without decreasing the transportation capacity.

  4. A Dereplication and Bioguided Discovery Approach to Reveal New Compounds from a Marine-Derived Fungus Stilbella fimetaria

    DEFF Research Database (Denmark)

    Kildgaard, Sara; Subko, Karolina; Phillips, Emma

    2017-01-01

    towards various cancer cell lines. Further media optimization led to increased production followed by the purification and bioactivity screening of several new and known pimarane-type diterpenoids. A known broad-spectrum antifungal compound, ilicicolin H, was purified along with two new analogues......A marine-derived Stilbella fimetaria fungal strain was screened for new bioactive compounds based on two different approaches: (i) bio-guided approach using cytotoxicity and antimicrobial bioassays; and (ii) dereplication based approach using liquid chromatography with both diode array detection...... aid in the dereplication process, since separate fractions displaying different bioactivities allowed a quick tentative identification of known antimicrobial compounds and of potential new analogues. A new pimarane-type diterpene, myrocin F, was discovered in trace amounts and displayed cytotoxicity...

  5. Linking Gambling and Trauma: A Phenomenological Hermeneutic Case Study Using Almaas' Transformation of Narcissism Approach

    Science.gov (United States)

    Nixon, Gary; Solowoniuk, Jason; Boni, Lauren Julia; Kalischuk, Ruth Grant

    2013-01-01

    The purpose of this article is to examine the phenomenon of pathological gambling and addiction from the perspective of writer and teacher A.H Almaas. By drawing on his Diamond Mind approach we trace the origin of addictive behaviors and pathological gambling to narcissistic wounding, which constitutes the loss of connection with the Essential…

  6. A multiscale analytical approach for bone remodeling simulations : linking scales from collagen to trabeculae

    NARCIS (Netherlands)

    Colloca, M.; Blanchard, R.; Hellmich, C.; Ito, K.; Rietbergen, van B.

    2014-01-01

    Bone is a dynamic and hierarchical porous material whose spatial and temporal mechanical properties can vary considerably due to differences in its microstructure and due to remodeling. Hence, a multiscale analytical approach, which combines bone structural information at multiple scales to the

  7. Linking genes to microbial growth kinetics: an integrated biochemical systems engineering approach

    NARCIS (Netherlands)

    Koutinas, M.; Kiparissides, A.; Silva-Rocha, R.; Lam, M.C.; Martins Dos Santos, V.A.P.; Lorenzo, de V.; Pistikopoulos, E.N.; Mantalaris, A.

    2011-01-01

    The majority of models describing the kinetic properties of a microorganism for a given substrate are unstructured and empirical. They are formulated in this manner so that the complex mechanism of cell growth is simplified. Herein, a novel approach for modelling microbial growth kinetics is

  8. Exploring the Link between Mind Wandering, Mindfulness, and Creativity: A Multidimensional Approach

    Science.gov (United States)

    Agnoli, Sergio; Vanucci, Manila; Pelagatti, Claudia; Corazza, Giovanni Emanuele

    2018-01-01

    Even if mind wandering (MW) and mindfulness have traditionally been intended as separate and antithetical constructs, the roles of these 2 mental states on creative behavior were jointly explored in this article. In particular, MW was analyzed in light of a recent approach suggesting a differentiation between deliberate and spontaneous MW, whereas…

  9. Linking Action Learning and Inter-Organisational Learning: The Learning Journey Approach

    Science.gov (United States)

    Schumacher, Thomas

    2015-01-01

    The article presents and illustrates the learning journey (LJ)--a new management development approach to inter-organisational learning based on observation, reflection and problem-solving. The LJ involves managers from different organisations and applies key concepts of action learning and systemic organisational development. Made up of…

  10. Linking Resource-Based Strategies to Customer-Focused Performance for Professional Services: A Structural Equation Modelling Approach

    Directory of Open Access Journals (Sweden)

    Ming-Lu Wu

    2013-12-01

    Full Text Available This paper links professional service firms’ resource-based strategies to their customer-focused performance for formulating service quality improvement priorities. The research applies the structural equation modelling approach to survey data from Hong Kong construction consultants to test some hypotheses. The study validates the various measures of firms’ resource-based strategies and customer-focused performance and bridges the gaps in firms’ organizational learning, core competences and customer-focused performance mediated by their strategic flexibility. The research results have practical implications for professional service firms to deploy resources appropriately to first enhance different competences and then improve customerfocused performance using their different competences.

  11. A control strategy for DC-link voltage control containing PV generation and energy storage — An intelligent approach

    OpenAIRE

    Rouzbehi, Kumars; Miranian, Arash; Candela García, José Ignacio; Luna Alloza, Álvaro; Rodríguez Cortés, Pedro

    2014-01-01

    In this paper, DC-link voltage control in DC microgrids with photovoltaic (PV) generation and battery, is addressed based on an intelligent approach. The proposed strategy is based on the modeling of the power interface, i.e. power electronic converter, located between the PV array, battery and DC bus, by use of measurement data. For this purpose, a local model network (LMN) is developed to model the converter and then a local linear control (LLC) strategy is designed based on the LMN. Simula...

  12. Linking Classroom Environment with At-Risk Engagement in Science: A Mixed Method Approach

    Science.gov (United States)

    Collins, Stephen Craig

    This explanatory sequential mixed-method study analyzed how the teacher created learning environment links to student engagement for students at-risk across five science classroom settings. The learning environment includes instructional strategies, differentiated instruction, positive learning environment, and an academically challenging environment. Quantitative and qualitative data were gathered in the form of self-reporting surveys and a follow-up interview. The researcher aimed to use the qualitative results to explain the quantitative data. The general research question was "What are the factors of the teacher-created learning environment that were best suited to maximize engagement of students at-risk?" Specifically explaining, (1) How do the measured level of teacher created learning environment link to the engagement level of students at-risk in science class? and (2) What relationship exists between the student perception of the science classroom environment and the level of behavioral, cognitive, emotional, and social engagement for students at-risk in science class? This study took place within a large school system with more than 20 high schools, most having 2000-3000 students. Participating students were sent to a panel hearing that determined them unfit for the regular educational setting, and were given the option of attending one of the two alternative schools within the county. Students in this alternative school were considered at-risk due to the fact that 98% received free and reduced lunch, 97% were minority population, and all have been suspended from the regular educational setting. Pairwise comparisons of the SPS questions between teachers using t-test from 107 students at-risk and 40 interviews suggest that each category of the learning environment affects the level of behavioral, cognitive, emotional, and social engagement in science class for students at-risk in an alternative school setting. Teachers with higher student perceptions of

  13. Enhancing Enterprise 2.0 Ecosystems Using Semantic Web and Linked Data Technologies:The SemSLATES Approach

    Science.gov (United States)

    Passant, Alexandre; Laublet, Philippe; Breslin, John G.; Decker, Stefan

    During the past few years, various organisations embraced the Enterprise 2.0 paradigms, providing their employees with new means to enhance collaboration and knowledge sharing in the workplace. However, while tools such as blogs, wikis, and principles like free-tagging or content syndication allow user-generated content to be more easily created and shared in the enterprise, in spite of some social issues, these new practices lead to various problems in terms of knowledge management. In this chapter, we provide an approach based on Semantic Web and Linked Data technologies for (1) integrating heterogeneous data from distinct Enterprise 2.0 applications, and (2) bridging the gap between raw text and machine-readable Linked Data. We discuss the theoretical background of our proposal as well as a practical case-study in enterprise, focusing on the various add-ons that have been provided to the original information system, as well as presenting how public Linked Open Data from the Web can be used to enhance existing Enterprise 2.0 ecosystems.

  14. A systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders.

    Science.gov (United States)

    Jiang, Peng; Scarpa, Joseph R; Fitzpatrick, Karrie; Losic, Bojan; Gao, Vance D; Hao, Ke; Summa, Keith C; Yang, He S; Zhang, Bin; Allada, Ravi; Vitaterna, Martha H; Turek, Fred W; Kasarskis, Andrew

    2015-05-05

    Sleep dysfunction and stress susceptibility are comorbid complex traits that often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multilevel organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J × A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type-specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests that the interplay among sleep, stress, and neuropathology emerges from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework for interrogating the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Theory of the multiphoton cascade transitions with two photon links: comparison of quantum electrodynamical and quantum mechanical approaches

    International Nuclear Information System (INIS)

    Zalialiutdinov, T; Baukina, Yu; Solovyev, D; Labzowsky, L

    2014-01-01

    The theory of multiphoton cascade transitions with two-photon links is considered within two different approaches: quantum electrodynamical (QED) and phenomenological quantum mechanical (QM). A problem of regularization of the cascade contributions is investigated in detail. It is argued that the correct regularization should include both initial and intermediate level widths in the singular energy denominators. This result follows both from the QED and from the QM approach. Particular transitions nl → 1s + 2γ with nl = 3s, 4s, 3d, 4d and nl → 1s + 3γ with nl = 3p, 4p are considered as examples. The importance of the proper cascade regularization is also demonstrated. (paper)

  16. 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

  17. A new approach to chromosome-wide analysis of X-linked markers identifies new associations in Asian and European case-parent triads of orofacial clefts.

    Directory of Open Access Journals (Sweden)

    Øivind Skare

    Full Text Available GWAS discoveries on the X-chromosome are underrepresented in the literature primarily because the analytical tools that have been applied were originally designed for autosomal markers. Our objective here is to employ a new robust and flexible tool for chromosome-wide analysis of X-linked markers in complex traits. Orofacial clefts are good candidates for such analysis because of the consistently observed excess of females with cleft palate only (CPO and excess of males with cleft lip with or without cleft palate (CL/P.Genotypes for 14,486 X-chromosome SNPs in 1,291 Asian and 1,118 European isolated cleft triads were available from a previously published GWAS. The R-package HAPLIN enables genome-wide-level analyses as well as statistical power simulations for a range of biologic scenarios. We analyzed isolated CL/P and isolated CPO for each ethnicity in HAPLIN, using a sliding-window approach to haplotype analysis and two different statistical models, with and without X-inactivation in females.There was a larger number of associations in the Asian versus the European sample, and similar to previous reports that have analyzed the same GWAS dataset using different methods, we identified associations with EFNB1/PJA1 and DMD. In addition, new associations were detected with several other genes, among which KLHL4, TBX22, CPXCR1 and BCOR were noteworthy because of their roles in clefting syndromes. A few of the associations were only detected by one particular X-inactivation model, whereas a few others were only detected in one sex.We found new support for the involvement of X-linked variants in isolated clefts. The associations were specific for ethnicity, sex and model parameterization, highlighting the need for flexible tools that are capable of detecting and estimating such effects. Further efforts are needed to verify and elucidate the potential roles of EFNB1/PJA1, KLHL4, TBX22, CPXCR1 and BCOR in isolated clefts.

  18. Linking occurrence and fitness to persistence: Habitat-based approach for endangered Greater Sage-Grouse

    Science.gov (United States)

    Aldridge, Cameron L.; Boyce, Mark S.

    2007-01-01

    Detailed empirical models predicting both species occurrence and fitness across a landscape are necessary to understand processes related to population persistence. Failure to consider both occurrence and fitness may result in incorrect assessments of habitat importance leading to inappropriate management strategies. We took a two-stage approach to identifying critical nesting and brood-rearing habitat for the endangered Greater Sage-Grouse (Centrocercus urophasianus) in Alberta at a landscape scale. First, we used logistic regression to develop spatial models predicting the relative probability of use (occurrence) for Sage-Grouse nests and broods. Secondly, we used Cox proportional hazards survival models to identify the most risky habitats across the landscape. We combined these two approaches to identify Sage-Grouse habitats that pose minimal risk of failure (source habitats) and attractive sink habitats that pose increased risk (ecological traps). Our models showed that Sage-Grouse select for heterogeneous patches of moderate sagebrush cover (quadratic relationship) and avoid anthropogenic edge habitat for nesting. Nests were more successful in heterogeneous habitats, but nest success was independent of anthropogenic features. Similarly, broods selected heterogeneous high-productivity habitats with sagebrush while avoiding human developments, cultivated cropland, and high densities of oil wells. Chick mortalities tended to occur in proximity to oil and gas developments and along riparian habitats. For nests and broods, respectively, approximately 10% and 5% of the study area was considered source habitat, whereas 19% and 15% of habitat was attractive sink habitat. Limited source habitats appear to be the main reason for poor nest success (39%) and low chick survival (12%). Our habitat models identify areas of protection priority and areas that require immediate management attention to enhance recruitment to secure the viability of this population. This novel

  19. A Bayesian Approach to the Overlap Analysis of Epidemiologically Linked Traits.

    Science.gov (United States)

    Asimit, Jennifer L; Panoutsopoulou, Kalliope; Wheeler, Eleanor; Berndt, Sonja I; Cordell, Heather J; Morris, Andrew P; Zeggini, Eleftheria; Barroso, Inês

    2015-12-01

    Diseases often cooccur in individuals more often than expected by chance, and may be explained by shared underlying genetic etiology. A common approach to genetic overlap analyses is to use summary genome-wide association study data to identify single-nucleotide polymorphisms (SNPs) that are associated with multiple traits at a selected P-value threshold. However, P-values do not account for differences in power, whereas Bayes' factors (BFs) do, and may be approximated using summary statistics. We use simulation studies to compare the power of frequentist and Bayesian approaches with overlap analyses, and to decide on appropriate thresholds for comparison between the two methods. It is empirically illustrated that BFs have the advantage over P-values of a decreasing type I error rate as study size increases for single-disease associations. Consequently, the overlap analysis of traits from different-sized studies encounters issues in fair P-value threshold selection, whereas BFs are adjusted automatically. Extensive simulations show that Bayesian overlap analyses tend to have higher power than those that assess association strength with P-values, particularly in low-power scenarios. Calibration tables between BFs and P-values are provided for a range of sample sizes, as well as an approximation approach for sample sizes that are not in the calibration table. Although P-values are sometimes thought more intuitive, these tables assist in removing the opaqueness of Bayesian thresholds and may also be used in the selection of a BF threshold to meet a certain type I error rate. An application of our methods is used to identify variants associated with both obesity and osteoarthritis. © 2015 The Authors. *Genetic Epidemiology published by Wiley Periodicals, Inc.

  20. New approach to training in citizen security from the social link university–community

    Directory of Open Access Journals (Sweden)

    Edicta Gregoria González-Leal

    2017-11-01

    Full Text Available This article bases the need for a new conception in the training approaches in the training institutions of citizen security professionals, due to the present changes in the 21st century at the state, regional and local level, where the protagonism of the same lies In responding to the new challenges, trends and challenges present in society. It also analyzes the significance of the university's social connection with the communities, so that the praxis of the students goes beyond the understanding of the problems to the search for possible alternatives for their solution, with the consequent social transformations that this bring along.

  1. Treatment wetlands in decentralised approaches for linking sanitation to energy and food security.

    Science.gov (United States)

    Langergraber, Guenter; Masi, Fabio

    2018-02-01

    Treatment wetlands (TWs) are engineered systems that mimic the processes in natural wetlands with the purpose of treating contaminated water. Being a simple and robust technology, TWs are applied worldwide to treat various types of water. Besides treated water for reuse, TWs can be used in resources-oriented sanitation systems for recovering nutrients and carbon, as well as for growing biomass for energy production. Additionally, TWs provide a large number of ecosystem services. Integrating green infrastructure into urban developments can thus facilitate circular economy approaches and has positive impacts on environment, economy and health.

  2. Determinants Linked to Family Business Sustainability in the UAE: An AHP Approach

    Directory of Open Access Journals (Sweden)

    Mohammed Oudah

    2018-01-01

    Full Text Available The purpose of this study is to identify and prioritise the various success factors linked to the sustainability of large and medium sized family businesses (FB in the United Arab Emirates (UAE. A well-researched methodology was used for the synthesis of priorities and the measurement of consistencies. The analytic hierarchy process (AHP model was developed with seven criteria and 15 sub-criteria gleaned from prior research. Data were collected using an interview-based survey conducted on twelve medium and large sized family firms in the UAE. The data collected were interpreted and a priority vector was assigned. The findings show that large family businesses in the UAE are aware of transition failure and have long-term planning for their future generations in place; however, they need to give more importance to family values and family capital. On the other hand, medium sized family businesses are less aware of transition failure and have limited long-term planning; they are more concerned with short-term returns. Therefore, they need to create and give more importance to succession planning, strategic planning and corporate governance to ensure their business longevity. The study highlights multi-generation family business sustainability, and identifies the major determinants that the family members and business leaders need to consider for their business continuity and survival. The model can be utilized by academics in family business sustainability studies. The findings interpreted can help policy makers and related associations develop various policies based on the specific factors found to run the family businesses in a sustainable manner. The research model had limited dimensions and the findings cannot be generalized. This study is the first to study the determinants of family business sustainability in the context of the UAE using the AHP model.

  3. ESIP's Earth Science Knowledge Graph (ESKG) Testbed Project: An Automatic Approach to Building Interdisciplinary Earth Science Knowledge Graphs to Improve Data Discovery

    Science.gov (United States)

    McGibbney, L. J.; Jiang, Y.; Burgess, A. B.

    2017-12-01

    Big Earth observation data have been produced, archived and made available online, but discovering the right data in a manner that precisely and efficiently satisfies user needs presents a significant challenge to the Earth Science (ES) community. An emerging trend in information retrieval community is to utilize knowledge graphs to assist users in quickly finding desired information from across knowledge sources. This is particularly prevalent within the fields of social media and complex multimodal information processing to name but a few, however building a domain-specific knowledge graph is labour-intensive and hard to keep up-to-date. In this work, we update our progress on the Earth Science Knowledge Graph (ESKG) project; an ESIP-funded testbed project which provides an automatic approach to building a dynamic knowledge graph for ES to improve interdisciplinary data discovery by leveraging implicit, latent existing knowledge present within across several U.S Federal Agencies e.g. NASA, NOAA and USGS. ESKG strengthens ties between observations and user communities by: 1) developing a knowledge graph derived from various sources e.g. Web pages, Web Services, etc. via natural language processing and knowledge extraction techniques; 2) allowing users to traverse, explore, query, reason and navigate ES data via knowledge graph interaction. ESKG has the potential to revolutionize the way in which ES communities interact with ES data in the open world through the entity, spatial and temporal linkages and characteristics that make it up. This project enables the advancement of ESIP collaboration areas including both Discovery and Semantic Technologies by putting graph information right at our fingertips in an interactive, modern manner and reducing the efforts to constructing ontology. To demonstrate the ESKG concept, we will demonstrate use of our framework across NASA JPL's PO.DAAC, NOAA's Earth Observation Requirements Evaluation System (EORES) and various USGS

  4. A Link-Based Cluster Ensemble Approach For Improved Gene Expression Data Analysis

    Directory of Open Access Journals (Sweden)

    P.Balaji

    2015-01-01

    Full Text Available Abstract It is difficult from possibilities to select a most suitable effective way of clustering algorithm and its dataset for a defined set of gene expression data because we have a huge number of ways and huge number of gene expressions. At present many researchers are preferring to use hierarchical clustering in different forms this is no more totally optimal. Cluster ensemble research can solve this type of problem by automatically merging multiple data partitions from a wide range of different clusterings of any dimensions to improve both the quality and robustness of the clustering result. But we have many existing ensemble approaches using an association matrix to condense sample-cluster and co-occurrence statistics and relations within the ensemble are encapsulated only at raw level while the existing among clusters are totally discriminated. Finding these missing associations can greatly expand the capability of those ensemble methodologies for microarray data clustering. We propose general K-means cluster ensemble approach for the clustering of general categorical data into required number of partitions.

  5. A reduction approach to improve the quantification of linked fault trees through binary decision diagrams

    International Nuclear Information System (INIS)

    Ibanez-Llano, Cristina; Rauzy, Antoine; Melendez, Enrique; Nieto, Francisco

    2010-01-01

    Over the last two decades binary decision diagrams have been applied successfully to improve Boolean reliability models. Conversely to the classical approach based on the computation of the MCS, the BDD approach involves no approximation in the quantification of the model and is able to handle correctly negative logic. However, when models are sufficiently large and complex, as for example the ones coming from the PSA studies of the nuclear industry, it begins to be unfeasible to compute the BDD within a reasonable amount of time and computer memory. Therefore, simplification or reduction of the full model has to be considered in some way to adapt the application of the BDD technology to the assessment of such models in practice. This paper proposes a reduction process based on using information provided by the set of the most relevant minimal cutsets of the model in order to perform the reduction directly on it. This allows controlling the degree of reduction and therefore the impact of such simplification on the final quantification results. This reduction is integrated in an incremental procedure that is compatible with the dynamic generation of the event trees and therefore adaptable to the recent dynamic developments and extensions of the PSA studies. The proposed method has been applied to a real case study, and the results obtained confirm that the reduction enables the BDD computation while maintaining accuracy.

  6. A reduction approach to improve the quantification of linked fault trees through binary decision diagrams

    Energy Technology Data Exchange (ETDEWEB)

    Ibanez-Llano, Cristina, E-mail: cristina.ibanez@iit.upcomillas.e [Instituto de Investigacion Tecnologica (IIT), Escuela Tecnica Superior de Ingenieria ICAI, Universidad Pontificia Comillas, C/Santa Cruz de Marcenado 26, 28015 Madrid (Spain); Rauzy, Antoine, E-mail: Antoine.RAUZY@3ds.co [Dassault Systemes, 10 rue Marcel Dassault CS 40501, 78946 Velizy Villacoublay, Cedex (France); Melendez, Enrique, E-mail: ema@csn.e [Consejo de Seguridad Nuclear (CSN), C/Justo Dorado 11, 28040 Madrid (Spain); Nieto, Francisco, E-mail: nieto@iit.upcomillas.e [Instituto de Investigacion Tecnologica (IIT), Escuela Tecnica Superior de Ingenieria ICAI, Universidad Pontificia Comillas, C/Santa Cruz de Marcenado 26, 28015 Madrid (Spain)

    2010-12-15

    Over the last two decades binary decision diagrams have been applied successfully to improve Boolean reliability models. Conversely to the classical approach based on the computation of the MCS, the BDD approach involves no approximation in the quantification of the model and is able to handle correctly negative logic. However, when models are sufficiently large and complex, as for example the ones coming from the PSA studies of the nuclear industry, it begins to be unfeasible to compute the BDD within a reasonable amount of time and computer memory. Therefore, simplification or reduction of the full model has to be considered in some way to adapt the application of the BDD technology to the assessment of such models in practice. This paper proposes a reduction process based on using information provided by the set of the most relevant minimal cutsets of the model in order to perform the reduction directly on it. This allows controlling the degree of reduction and therefore the impact of such simplification on the final quantification results. This reduction is integrated in an incremental procedure that is compatible with the dynamic generation of the event trees and therefore adaptable to the recent dynamic developments and extensions of the PSA studies. The proposed method has been applied to a real case study, and the results obtained confirm that the reduction enables the BDD computation while maintaining accuracy.

  7. An integrated approach for the knowledge discovery in computer simulation models with a multi-dimensional parameter space

    Energy Technology Data Exchange (ETDEWEB)

    Khawli, Toufik Al; Eppelt, Urs; Hermanns, Torsten [RWTH Aachen University, Chair for Nonlinear Dynamics, Steinbachstr. 15, 52047 Aachen (Germany); Gebhardt, Sascha [RWTH Aachen University, Virtual Reality Group, IT Center, Seffenter Weg 23, 52074 Aachen (Germany); Kuhlen, Torsten [Forschungszentrum Jülich GmbH, Institute for Advanced Simulation (IAS), Jülich Supercomputing Centre (JSC), Wilhelm-Johnen-Straße, 52425 Jülich (Germany); Schulz, Wolfgang [Fraunhofer, ILT Laser Technology, Steinbachstr. 15, 52047 Aachen (Germany)

    2016-06-08

    In production industries, parameter identification, sensitivity analysis and multi-dimensional visualization are vital steps in the planning process for achieving optimal designs and gaining valuable information. Sensitivity analysis and visualization can help in identifying the most-influential parameters and quantify their contribution to the model output, reduce the model complexity, and enhance the understanding of the model behavior. Typically, this requires a large number of simulations, which can be both very expensive and time consuming when the simulation models are numerically complex and the number of parameter inputs increases. There are three main constituent parts in this work. The first part is to substitute the numerical, physical model by an accurate surrogate model, the so-called metamodel. The second part includes a multi-dimensional visualization approach for the visual exploration of metamodels. In the third part, the metamodel is used to provide the two global sensitivity measures: i) the Elementary Effect for screening the parameters, and ii) the variance decomposition method for calculating the Sobol indices that quantify both the main and interaction effects. The application of the proposed approach is illustrated with an industrial application with the goal of optimizing a drilling process using a Gaussian laser beam.

  8. Characterizing the Surface Connectivity of Depressional Wetlands: Linking Remote Sensing and Hydrologic Modeling Approaches

    Science.gov (United States)

    Christensen, J.; Evenson, G. R.; Vanderhoof, M.; Wu, Q.; Golden, H. E.; Lane, C.

    2017-12-01

    Surface connectivity of wetlands in the 700,000 km2 Prairie Pothole Region of North America (PPR) can occur through fill-spill and fill-merge mechanisms, with some wetlands eventually spilling into stream/river systems. These wetland-to-wetland and wetland-to-stream connections vary both spatially and temporally in PPR watersheds and are important to understanding hydrologic and biogeochemical processes in the landscape. To explore how to best characterize spatial and temporal variability in aquatic connectivity, we compared three approaches, 1) hydrological modeling alone, 2) remotely-sensed data alone, and 3) integrating remotely-sensed data into a hydrological model. These approaches were tested in the Pipestem Creek Watershed, North Dakota across a drought to deluge cycle (1990-2011). A Soil and Water Assessment Tool (SWAT) model was modified to include the water storage capacity of individual non-floodplain wetlands identified in the National Wetland Inventory (NWI) dataset. The SWAT-NWI model simulated the water balance and storage of each wetland and the temporal variability of their hydrologic connections between wetlands during the 21-year study period. However, SWAT-NWI only accounted for fill-spill, and did not allow for the expansion and merging of wetlands situated within larger depressions. Alternatively, we assessed the occurrence of fill-merge mechanisms using inundation maps derived from Landsat images on 19 cloud-free days during the 21 years. We found fill-merge mechanisms to be prevalent across the Pipestem watershed during times of deluge. The SWAT-NWI model was then modified to use LiDAR-derived depressions that account for the potential maximum depression extent, including the merging of smaller wetlands. The inundation maps were used to evaluate the ability of the SWAT-depression model to simulate fill-merge dynamics in addition to fill-spill dynamics throughout the study watershed. Ultimately, using remote sensing to inform and validate

  9. Linking Tree Growth Response to Measured Microclimate - A Field Based Approach

    Science.gov (United States)

    Martin, J. T.; Hoylman, Z. H.; Looker, N. T.; Jencso, K. G.; Hu, J.

    2015-12-01

    climate and annual ring formation, and suggest a rather immediate growth response to critical micro-meteorological conditions occurring at different times across the landscape by linking the timing and magnitude of tree growth responses to in situ measurements of environmental conditions.

  10. A dual transcript-discovery approach to improve the delimitation of gene features from RNA-seq data in the chicken model

    Directory of Open Access Journals (Sweden)

    Mickael Orgeur

    2018-01-01

    Full Text Available The sequence of the chicken genome, like several other draft genome sequences, is presently not fully covered. Gaps, contigs assigned with low confidence and uncharacterized chromosomes result in gene fragmentation and imprecise gene annotation. Transcript abundance estimation from RNA sequencing (RNA-seq data relies on read quality, library complexity and expression normalization. In addition, the quality of the genome sequence used to map sequencing reads, and the gene annotation that defines gene features, must also be taken into account. A partially covered genome sequence causes the loss of sequencing reads from the mapping step, while an inaccurate definition of gene features induces imprecise read counts from the assignment step. Both steps can significantly bias interpretation of RNA-seq data. Here, we describe a dual transcript-discovery approach combining a genome-guided gene prediction and a de novo transcriptome assembly. This dual approach enabled us to increase the assignment rate of RNA-seq data by nearly 20% as compared to when using only the chicken reference annotation, contributing therefore to a more accurate estimation of transcript abundance. More generally, this strategy could be applied to any organism with partial genome sequence and/or lacking a manually-curated reference annotation in order to improve the accuracy of gene expression studies.

  11. Discovery of the first maize-infecting mastrevirus in the Americas using a vector-enabled metagenomics approach.

    Science.gov (United States)

    Fontenele, Rafaela S; Alves-Freitas, Dione M T; Silva, Pedro I T; Foresti, Josemar; Silva, Paulo R; Godinho, Márcio T; Varsani, Arvind; Ribeiro, Simone G

    2018-01-01

    The genus Mastrevirus (family Geminiviridae) is composed of single-stranded DNA viruses that infect mono- and dicotyledonous plants and are transmitted by leafhoppers. In South America, there have been only two previous reports of mastreviruses, both identified in sweet potatoes (from Peru and Uruguay). As part of a general viral surveillance program, we used a vector-enabled metagenomics (VEM) approach and sampled leafhoppers (Dalbulus maidis) in Itumbiara (State of Goiás), Brazil. High-throughput sequencing of viral DNA purified from the leafhopper sample revealed mastrevirus-like contigs. Using a set of abutting primers, a 2746-nt circular genome was recovered. The circular genome has a typical mastrevirus genome organization and shares 99% pairwise identity with the one from the leafhopper. This is the first report of a maize-infecting mastrevirus in the Americas, the first identified in a non-vegetatively propagated mastrevirus host in South America, and the first mastrevirus to be identified in Brazil.

  12. Discovery Mondays

    CERN Multimedia

    2003-01-01

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

  13. Linking flood peak, flood volume and inundation extent: a DEM-based approach

    Science.gov (United States)

    Rebolho, Cédric; Furusho-Percot, Carina; Blaquière, Simon; Brettschneider, Marco; Andréassian, Vazken

    2017-04-01

    Traditionally, flood inundation maps are computed based on the Shallow Water Equations (SWE) in one or two dimensions, with various simplifications that have proved to give good results. However, the complexity of the SWEs often requires a numerical resolution which can need long computing time, as well as detailed cross section data: this often results in restricting these models to rather small areas abundant with high quality data. This, along with the necessity for fast inundation mapping, are the reason why rapid inundation models are being designed, working for (almost) any river with a minimum amount of data and, above all, easily available data. Our model tries to follow this path by using a 100m DEM over France from which are extracted a drainage network and the associated drainage areas. It is based on two pre-existing methods: (1) SHYREG (Arnaud et al.,2013), a regionalized approach used to calculate the 2-year and 10-year flood quantiles (used as approximated bankfull flow and maximum discharge, respectively) for each river pixel of the DEM (below a 10 000 km2 drainage area) and (2) SOCOSE (Mailhol,1980), which gives, amongst other things, an empirical formula of a characteristic flood duration (for each pixel) based on catchment area, average precipitation and temperature. An overflow volume for each river pixel is extracted from a triangular shaped synthetic hydrograph designed with SHYREG quantiles and SOCOSE flood duration. The volume is then spread from downstream to upstream one river pixel at a time. When the entire hydrographic network is processed, the model stops and generates a map of potential inundation area associated with the 10-year flood quantile. Our model can also be calibrated using past-events inundation maps by adjusting two parameters, one which modifies the overflow duration, and the other, equivalent to a minimum drainage area for river pixels to be flooded. Thus, in calibration on a sample of 42 basins, the first draft of the

  14. Linking Genes and Brain Development of Honeybee Workers: A Whole-Transcriptome Approach.

    Directory of Open Access Journals (Sweden)

    Christina Vleurinck

    Full Text Available Honeybees live in complex societies whose capabilities far exceed those of the sum of their single members. This social synergism is achieved mainly by the worker bees, which form a female caste. The worker bees display diverse collaborative behaviors and engage in different behavioral tasks, which are controlled by the central nervous system (CNS. The development of the worker brain is determined by the female sex and the worker caste determination signal. Here, we report on genes that are controlled by sex or by caste during differentiation of the worker's pupal brain. We sequenced and compared transcriptomes from the pupal brains of honeybee workers, queens and drones. We detected 333 genes that are differently expressed and 519 genes that are differentially spliced between the sexes, and 1760 genes that are differentially expressed and 692 genes that are differentially spliced between castes. We further found that 403 genes are differentially regulated by both the sex and caste signals, providing evidence of the integration of both signals through differential gene regulation. In this gene set, we found that the molecular processes of restructuring the cell shape and cell-to-cell signaling are overrepresented. Our approach identified candidate genes that may be involved in brain differentiation that ensures the various social worker behaviors.

  15. A System-Wide Approach to Identify the Mechanisms of Barnacle Attachment: Toward the Discovery of New Antifouling Compounds

    KAUST Repository

    Al-Aqeel, Sarah

    2015-11-01

    Biofouling is a significant economic problem, particularly for marine and offshore oil industries. The acorn barnacle (Amphibalanus (Balanus) amphitrite) is the main biofouling organism in marine environments. Environmental conditions, the physiology of the biofouling organism, the surrounding microbial community, and the properties of the substratum can all influence the attachment of biofouling organisms to substrates. My dissertation investigated the biological processes involved in B. amphitrite development and attachment in the unique environment of the Red Sea, where the average water surface temperature is 34°C and the salinity reaches 41‰. I profiled the transcriptome and proteome of B. amphitrite at different life stages (nauplius II, nauplius VI, and cyprid) and identified 65,784 expressed contigs and 1387 expressed proteins by quantitative proteomics. During the planktonic stage, genes related to osmotic stress, salt stress, the hyperosmotic response, and the Wnt signaling pathway were strongly up-regulated, hereas genes related to the MAPK pathway, lipid metabolism, and cuticle development were down-regulated. In the transition from the nauplius VI to cyprid stages, there was up-regulation of genes involved in blood coagulation, cuticle development, and eggshell formation, and down-regulation of genes in the nitric oxide pathway, which stimulates the swimming and feeding responses of marine invertebrates. This system-wide integrated approach elucidated the development and attachment pathways important in B. amphitrite. Enzymes and metabolites in these pathways are potential molecular targets for the development of new antifouling compounds.

  16. Discovery of Novel Inhibitors for Nek6 Protein through Homology Model Assisted Structure Based Virtual Screening and Molecular Docking Approaches

    Directory of Open Access Journals (Sweden)

    P. Srinivasan

    2014-01-01

    Full Text Available Nek6 is a member of the NIMA (never in mitosis, gene A-related serine/threonine kinase family that plays an important role in the initiation of mitotic cell cycle progression. This work is an attempt to emphasize the structural and functional relationship of Nek6 protein based on homology modeling and binding pocket analysis. The three-dimensional structure of Nek6 was constructed by molecular modeling studies and the best model was further assessed by PROCHECK, ProSA, and ERRAT plot in order to analyze the quality and consistency of generated model. The overall quality of computed model showed 87.4% amino acid residues under the favored region. A 3 ns molecular dynamics simulation confirmed that the structure was reliable and stable. Two lead compounds (Binding database ID: 15666, 18602 were retrieved through structure-based virtual screening and induced fit docking approaches as novel Nek6 inhibitors. Hence, we concluded that the potential compounds may act as new leads for Nek6 inhibitors designing.

  17. Cancer immunogenomic approach to neoantigen discovery in a checkpoint blockade responsive murine model of oral cavity squamous cell carcinoma

    Science.gov (United States)

    Zolkind, Paul; Przybylski, Dariusz; Marjanovic, Nemanja; Nguyen, Lan; Lin, Tianxiang; Johanns, Tanner; Alexandrov, Anton; Zhou, Liye; Allen, Clint T.; Miceli, Alexander P.; Schreiber, Robert D.; Artyomov, Maxim; Dunn, Gavin P.; Uppaluri, Ravindra

    2018-01-01

    Head and neck squamous cell carcinomas (HNSCC) are an ideal immunotherapy target due to their high mutation burden and frequent infiltration with lymphocytes. Preclinical models to investigate targeted and combination therapies as well as defining biomarkers to guide treatment represent an important need in the field. Immunogenomics approaches have illuminated the role of mutation-derived tumor neoantigens as potential biomarkers of response to checkpoint blockade as well as representing therapeutic vaccines. Here, we aimed to define a platform for checkpoint and other immunotherapy studies using syngeneic HNSCC cell line models (MOC2 and MOC22), and evaluated the association between mutation burden, predicted neoantigen landscape, infiltrating T cell populations and responsiveness of tumors to anti-PD1 therapy. We defined dramatic hematopoietic cell transcriptomic alterations in the MOC22 anti-PD1 responsive model in both tumor and draining lymph nodes. Using a cancer immunogenomics pipeline and validation with ELISPOT and tetramer analysis, we identified the H-2Kb-restricted ICAM1P315L (mICAM1) as a neoantigen in MOC22. Finally, we demonstrated that mICAM1 vaccination was able to protect against MOC22 tumor development defining mICAM1 as a bona fide neoantigen. Together these data define a pre-clinical HNSCC model system that provides a foundation for future investigations into combination and novel therapeutics. PMID:29423108

  18. Novel aptamer-linked nanoconjugate approach for detection of waterborne bacterial pathogens: an update

    International Nuclear Information System (INIS)

    Singh, Gulshan; Manohar, Murli; Adegoke, Anthony Ayodeji; Stenström, Thor Axel; Shanker, Rishi

    2017-01-01

    The lack of microbiologically safe water in underdeveloped nations is the prime cause of infectious disease outbreaks. The need for the specific identification and detection of microorganisms encourages the development of advanced, rapid, sensitive and highly specific methods for the monitoring of pathogens and management of potential risk to human health. The rapid molecular assays based on detection of specific molecular signatures offer advantages over conventional methods in terms of specificity and sensitivity but require complex instrumentation and skilled personnel. Nanotechnology is an emerging area and provides a robust approach for the identification of pathogenic microorganism utilizing the peculiar properties of nanomaterials, i.e. small size (1–100 nm) and large surface area. This emerging technology promises to fulfill the urgent need of a novel strategy to enhance the bacterial identification and quantitation in the environment. In this context, the peculiar properties of gold nanoparticles, their plasmonic shifts, and changes in magnetic properties have been utilized for the simple and cost-effective detection of bacterial nucleic acids, antigens and toxins with quite improved sensitivity. One of the promising leads to develop an advance detection method might be the coupling of nucleic acid aptamers (capable of interacting specifically with bacteria, protozoa, and viruses) with nanomaterials. Such aptamer-nano conjugate can be used for the specific recognition of infectious agents in different environmental matrices. This review summarizes the application of nanotechnology in the area of pathogen detection and discusses the prospects of coupling nucleic acid aptamers with nanoparticles for the specific detection of targeted pathogens.

  19. Novel aptamer-linked nanoconjugate approach for detection of waterborne bacterial pathogens: an update

    Science.gov (United States)

    Singh, Gulshan; Manohar, Murli; Adegoke, Anthony Ayodeji; Stenström, Thor Axel; Shanker, Rishi

    2017-01-01

    The lack of microbiologically safe water in underdeveloped nations is the prime cause of infectious disease outbreaks. The need for the specific identification and detection of microorganisms encourages the development of advanced, rapid, sensitive and highly specific methods for the monitoring of pathogens and management of potential risk to human health. The rapid molecular assays based on detection of specific molecular signatures offer advantages over conventional methods in terms of specificity and sensitivity but require complex instrumentation and skilled personnel. Nanotechnology is an emerging area and provides a robust approach for the identification of pathogenic microorganism utilizing the peculiar properties of nanomaterials, i.e. small size (1-100 nm) and large surface area. This emerging technology promises to fulfill the urgent need of a novel strategy to enhance the bacterial identification and quantitation in the environment. In this context, the peculiar properties of gold nanoparticles, their plasmonic shifts, and changes in magnetic properties have been utilized for the simple and cost-effective detection of bacterial nucleic acids, antigens and toxins with quite improved sensitivity. One of the promising leads to develop an advance detection method might be the coupling of nucleic acid aptamers (capable of interacting specifically with bacteria, protozoa, and viruses) with nanomaterials. Such aptamer-nano conjugate can be used for the specific recognition of infectious agents in different environmental matrices. This review summarizes the application of nanotechnology in the area of pathogen detection and discusses the prospects of coupling nucleic acid aptamers with nanoparticles for the specific detection of targeted pathogens.

  20. Novel aptamer-linked nanoconjugate approach for detection of waterborne bacterial pathogens: an update

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Gulshan, E-mail: gsingh.gulshan@gmail.com [Durban University of Technology, Institute for Water and Wastewater Technology (IWWT) (South Africa); Manohar, Murli [Jamia Hamdard (Hamdard University), Department of Biochemistry (India); Adegoke, Anthony Ayodeji; Stenström, Thor Axel [Durban University of Technology, Institute for Water and Wastewater Technology (IWWT) (South Africa); Shanker, Rishi [Ahmedabad University, Division of Biological & Life Sciences, School of Arts & Sciences (India)

    2017-01-15

    The lack of microbiologically safe water in underdeveloped nations is the prime cause of infectious disease outbreaks. The need for the specific identification and detection of microorganisms encourages the development of advanced, rapid, sensitive and highly specific methods for the monitoring of pathogens and management of potential risk to human health. The rapid molecular assays based on detection of specific molecular signatures offer advantages over conventional methods in terms of specificity and sensitivity but require complex instrumentation and skilled personnel. Nanotechnology is an emerging area and provides a robust approach for the identification of pathogenic microorganism utilizing the peculiar properties of nanomaterials, i.e. small size (1–100 nm) and large surface area. This emerging technology promises to fulfill the urgent need of a novel strategy to enhance the bacterial identification and quantitation in the environment. In this context, the peculiar properties of gold nanoparticles, their plasmonic shifts, and changes in magnetic properties have been utilized for the simple and cost-effective detection of bacterial nucleic acids, antigens and toxins with quite improved sensitivity. One of the promising leads to develop an advance detection method might be the coupling of nucleic acid aptamers (capable of interacting specifically with bacteria, protozoa, and viruses) with nanomaterials. Such aptamer-nano conjugate can be used for the specific recognition of infectious agents in different environmental matrices. This review summarizes the application of nanotechnology in the area of pathogen detection and discusses the prospects of coupling nucleic acid aptamers with nanoparticles for the specific detection of targeted pathogens.

  1. 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.

  2. An integrative pharmacological approach to radio telemetry and blood sampling in pharmaceutical drug discovery and safety assessment.

    Science.gov (United States)

    Litwin, Dennis C; Lengel, David J; Kamendi, Harriet W; Bialecki, Russell A

    2011-01-18

    A successful integration of the automated blood sampling (ABS) and telemetry (ABST) system is described. The new ABST system facilitates concomitant collection of physiological variables with blood and urine samples for determination of drug concentrations and other biochemical measures in the same rat without handling artifact. Integration was achieved by designing a 13 inch circular receiving antenna that operates as a plug-in replacement for the existing pair of DSI's orthogonal antennas which is compatible with the rotating cage and open floor design of the BASi Culex® ABS system. The circular receiving antenna's electrical configuration consists of a pair of electrically orthogonal half-toroids that reinforce reception of a dipole transmitter operating within the coil's interior while reducing both external noise pickup and interference from other adjacent dipole transmitters. For validation, measured baclofen concentration (ABST vs. satellite (μM): 69.6 ± 23.8 vs. 76.6 ± 19.5, p = NS) and mean arterial pressure (ABST vs. traditional DSI telemetry (mm Hg): 150 ± 5 vs.147 ± 4, p = NS) variables were quantitatively and qualitatively similar between rats housed in the ABST system and traditional home cage approaches. The ABST system offers unique advantages over traditional between-group study paradigms that include improved data quality and significantly reduced animal use. The superior within-group model facilitates assessment of multiple physiological and biochemical responses to test compounds in the same animal. The ABST also provides opportunities to evaluate temporal relations between parameters and to investigate anomalous outlier events because drug concentrations, physiological and biochemical measures for each animal are available for comparisons.

  3. Spiraling in Urban Streams: A Novel Approach to Link Geomorphic Structure with Ecosystem Function

    Science.gov (United States)

    Bean, R. A.; Lafrenz, M. D.

    2011-12-01

    The goal of this study is to quantify the relationship between channel complexity and nutrient spiraling along several reaches of an urbanized watershed in Portland, Oregon. Much research points to the effect urbanization has on watershed hydrology and nutrient loading at the watershed scale for various sized catchments. However the flux of nutrients over short reaches within a stream channel has been less studied because of the effort and costs associated with fieldwork and subsequent laboratory analysis of both surface and hyporheic water samples. In this study we explore a novel approach at capturing connectivity though nutrient spiraling along several short reaches (less than 100-meter) within the highly urbanized Fanno Creek watershed (4400 hectares). We measure channel complexity-sinuosity, bed material texture, organic matter-and use these measurements to determine spatial autocorrelation of 50 reaches in Fanno Creek, a small, urban watershed in Portland, Oregon. Using ion-selective electrodes, the fluxes of nitrate and ammonia are measured within each reach, which when combined with channel geometry and velocity measurements allow us to transform the values of nitrate and ammonia fluxes into spiraling metrics. Along each sampled reach, we collected three surface water samples to characterize nutrient amounts at the upstream, midstream, and downstream position of the reach. Two additional water samples were taken from the left and right bank hyporheic zones at a depth just below the armor layer of the channel bed using mini-piezometers and a hand-pumped vacuum device, which we constructed for this purpose. Adjacent to the hyporheic samples soil cores were collected and analyzed for organic matter composition, bulk density, and texture. We hypothesize that spiral metrics will respond significantly to the measured channel complexity values and will be a more robust predictor of nutrient flux than land cover characteristics in the area draining to each reach

  4. Linking soil chemistry, treeline shifts and climate change: scenario modeling using an experimental approach

    Science.gov (United States)

    Mavris, Christian; Furrer, Gerhard; Anderson, Susanne; Blum, Alex; Wells, Aaron; Dahms, Dennis; Egli, Markus

    2014-05-01

    changing conditions. Our findings suggest that one of the controlling factors in nutrient release is the capacity of ion diffusion, mostly given by the activity of clay minerals and organic matter. (a) Burga, C., Krüsi, B., Egli, M., Wernli, M., Elsener, S., Ziefle, M., Fischer, T., Mavris, C.. Plant succession and soil development on the foreland of the Morteratsch glacier (Pontresina, Switzerland): Straight forward or chaotic? Flora 205 (2010) 561-576 (b) Dahms, D. Relative and Numeric Age Data for Pleistocene Glacial Deposits and Diamictons in and near Sinks Canyon, Wind River Range, Wyoming, U.S.A. AAAR 36, 1 (2004) 59-77 (c) Egli, M., Dahms, D., Norton, K. Soil formation rates on silicate parent material in alpine environments: Different approaches-different results? Geoderma 213 (2014) 320-333 (d) Furrer, G., von Gunten, U., Zobrist, J. Steady-state modelling of biogeochemical processes in columns with aquifer material: 1. Speciation and mass balances. Chemical Geology 133 (1996) 15-28 (e) von Gunten, U, Furrer, G. Steady-state modelling of biogeochemical processes in columns with aquifer material: 2. Dynamics of iron-sulfur interactions. Chemical Geology 167 (2000) 271-284

  5. A "genome-to-lead" approach for insecticide discovery: pharmacological characterization and screening of Aedes aegypti D(1-like dopamine receptors.

    Directory of Open Access Journals (Sweden)

    Jason M Meyer

    2012-01-01

    Full Text Available BACKGROUND: Many neglected tropical infectious diseases affecting humans are transmitted by arthropods such as mosquitoes and ticks. New mode-of-action chemistries are urgently sought to enhance vector management practices in countries where arthropod-borne diseases are endemic, especially where vector populations have acquired widespread resistance to insecticides. METHODOLOGY/PRINCIPAL FINDINGS: We describe a "genome-to-lead" approach for insecticide discovery that incorporates the first reported chemical screen of a G protein-coupled receptor (GPCR mined from a mosquito genome. A combination of molecular and pharmacological studies was used to functionally characterize two dopamine receptors (AaDOP1 and AaDOP2 from the yellow fever mosquito, Aedes aegypti. Sequence analyses indicated that these receptors are orthologous to arthropod D(1-like (Gα(s-coupled receptors, but share less than 55% amino acid identity in conserved domains with mammalian dopamine receptors. Heterologous expression of AaDOP1 and AaDOP2 in HEK293 cells revealed dose-dependent responses to dopamine (EC(50: AaDOP1 = 3.1±1.1 nM; AaDOP2 = 240±16 nM. Interestingly, only AaDOP1 exhibited sensitivity to epinephrine (EC(50 = 5.8±1.5 nM and norepinephrine (EC(50 = 760±180 nM, while neither receptor was activated by other biogenic amines tested. Differential responses were observed between these receptors regarding their sensitivity to dopamine agonists and antagonists, level of maximal stimulation, and constitutive activity. Subsequently, a chemical library screen was implemented to discover lead chemistries active at AaDOP2. Fifty-one compounds were identified as "hits," and follow-up validation assays confirmed the antagonistic effect of selected compounds at AaDOP2. In vitro comparison studies between AaDOP2 and the human D(1 dopamine receptor (hD(1 revealed markedly different pharmacological profiles and identified amitriptyline and doxepin as AaDOP2

  6. Using a linked data approach to aid development of a metadata portal to support Marine Strategy Framework Directive (MSFD) implementation

    Science.gov (United States)

    Wood, Chris

    2016-04-01

    Under the Marine Strategy Framework Directive (MSFD), EU Member States are mandated to achieve or maintain 'Good Environmental Status' (GES) in their marine areas by 2020, through a series of Programme of Measures (PoMs). The Celtic Seas Partnership (CSP), an EU LIFE+ project, aims to support policy makers, special-interest groups, users of the marine environment, and other interested stakeholders on MSFD implementation in the Celtic Seas geographical area. As part of this support, a metadata portal has been built to provide a signposting service to datasets that are relevant to MSFD within the Celtic Seas. To ensure that the metadata has the widest possible reach, a linked data approach was employed to construct the database. Although the metadata are stored in a traditional RDBS, the metadata are exposed as linked data via the D2RQ platform, allowing virtual RDF graphs to be generated. SPARQL queries can be executed against the end-point allowing any user to manipulate the metadata. D2RQ's mapping language, based on turtle, was used to map a wide range of relevant ontologies to the metadata (e.g. The Provenance Ontology (prov-o), Ocean Data Ontology (odo), Dublin Core Elements and Terms (dc & dcterms), Friend of a Friend (foaf), and Geospatial ontologies (geo)) allowing users to browse the metadata, either via SPARQL queries or by using D2RQ's HTML interface. The metadata were further enhanced by mapping relevant parameters to the NERC Vocabulary Server, itself built on a SPARQL endpoint. Additionally, a custom web front-end was built to enable users to browse the metadata and express queries through an intuitive graphical user interface that requires no prior knowledge of SPARQL. As well as providing means to browse the data via MSFD-related parameters (Descriptor, Criteria, and Indicator), the metadata records include the dataset's country of origin, the list of organisations involved in the management of the data, and links to any relevant INSPIRE

  7. Working with Data: Discovering Knowledge through Mining and Analysis; Systematic Knowledge Management and Knowledge Discovery; Text Mining; Methodological Approach in Discovering User Search Patterns through Web Log Analysis; Knowledge Discovery in Databases Using Formal Concept Analysis; Knowledge Discovery with a Little Perspective.

    Science.gov (United States)

    Qin, Jian; Jurisica, Igor; Liddy, Elizabeth D.; Jansen, Bernard J; Spink, Amanda; Priss, Uta; Norton, Melanie J.

    2000-01-01

    These six articles discuss knowledge discovery in databases (KDD). Topics include data mining; knowledge management systems; applications of knowledge discovery; text and Web mining; text mining and information retrieval; user search patterns through Web log analysis; concept analysis; data collection; and data structure inconsistency. (LRW)

  8. A desirability-based multi objective approach for the virtual screening discovery of broad-spectrum anti-gastric cancer agents.

    Directory of Open Access Journals (Sweden)

    Yunierkis Perez-Castillo

    Full Text Available Gastric cancer is the third leading cause of cancer-related mortality worldwide and despite advances in prevention, diagnosis and therapy, it is still regarded as a global health concern. The efficacy of the therapies for gastric cancer is limited by a poor response to currently available therapeutic regimens. One of the reasons that may explain these poor clinical outcomes is the highly heterogeneous nature of this disease. In this sense, it is essential to discover new molecular agents capable of targeting various gastric cancer subtypes simultaneously. Here, we present a multi-objective approach for the ligand-based virtual screening discovery of chemical compounds simultaneously active against the gastric cancer cell lines AGS, NCI-N87 and SNU-1. The proposed approach relays in a novel methodology based on the development of ensemble models for the bioactivity prediction against each individual gastric cancer cell line. The methodology includes the aggregation of one ensemble per cell line using a desirability-based algorithm into virtual screening protocols. Our research leads to the proposal of a multi-targeted virtual screening protocol able to achieve high enrichment of known chemicals with anti-gastric cancer activity. Specifically, our results indicate that, using the proposed protocol, it is possible to retrieve almost 20 more times multi-targeted compounds in the first 1% of the ranked list than what is expected from a uniform distribution of the active ones in the virtual screening database. More importantly, the proposed protocol attains an outstanding initial enrichment of known multi-targeted anti-gastric cancer agents.

  9. A FAIR-Based Approach to Enhancing the Discovery and Re-Use of Transcriptomic Data Assets for Nuclear Receptor Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Scott A. Ochsner

    2017-03-01

    Full Text Available Public transcriptomic assets in the nuclear receptor (NR signaling field hold considerable collective potential for exposing underappreciated aspects of NR regulation of gene expression. This potential is undermined however by a series of enduring informatic pain points that retard the routine re-use of these datasets. Here we describe a coordinated biocuration and web development approach to redress this situation that is closely aligned with ideals articulated in the FAIR (findable, accessible, interoperable, re-usable principles on data stewardship. To improve findability, biocurators engage authors of studies in collaborating journals to secure datasets for deposition in public archives. Annotated derivatives of the archived datasets are assigned digital object identifiers and regulatory molecule identifiers that support persistent linkages between datasets and their associated research articles, integration in relevant records in gene and small molecule knowledgebases, and indexing by dataset search engines. To enhance their accessibility and interoperability, datasets are visualizable in responsively designed web pages, retrievable in machine-readable spreadsheets, or through an application programming interface. Re-use of the datasets is supported by their interrogation as a universe of data points through the Transcriptomine search engine, highlighting transcriptional intersections between NR signaling pathways, physiological processes and disease states. We illustrate the value of our approach in connecting disparate research communities using a use case of persistent interoperability between the Nuclear Receptor Signaling Atlas and the Pharmacogenomics Knowledgebase. Our FAIR-aligned model demonstrates the enduring value of discovery-scale datasets that accrues from their systematic compilation, biocuration and distribution across the digital biomedical research enterprise.

  10. 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

  11. How to link geography, cross-curricular approach and inquiry in science education at the primary schools

    Science.gov (United States)

    Karvánková, Petra; Popjaková, Dagmar

    2018-05-01

    Pupil research in school lessons in the sense of Inquiry-Based Education (IBE) is one of the constructivist approaches to education. Inquiry strengthens the positive approach of pupils to natural science subjects, encouraging them to study phenomena and processes taking place in the natural environment around them and use the acquired knowledge in their practical life. Geography as a school subject, due to the multidisciplinary nature of geography as a science, is close to natural sciences as well. This is because of the broadness of the subject of geographical studies, the complex (natural and cultural) landscape. The close links of geography to all cross-sectional themes make it a good support for teaching classical science subjects at schools such as mathematics, physics, chemistry or biology, environmental education. Moreover, the field teaching is one of the strong assets of the implementation of IBE in the school geography. Presented case study on the 'effect of noise on the surroundings' explores the facts mentioned above, in geography teaching. It verifies the pupils' knowledge and skills to adopt the basic principles of IBE in the practice. At the same time, it presents the concrete experiences how the children master the individual stages of IBE during the process of education.

  12. Alzheimer’s Disease and HLA-A2: Linking Neurodegenerative to Immune Processes through an In Silico Approach

    Directory of Open Access Journals (Sweden)

    Ricardo A. Cifuentes

    2014-01-01

    Full Text Available There is a controversial relationship between HLA-A2 and Alzheimer’s disease (AD. It has been suggested a modifier effect on the risk that depends on genetic loadings. Thus, the aims of this study were to evaluate this relationship and to reveal genes associated with both concepts the HLA-A gene and AD. Consequently, we did first a classical systematic review and a meta-analysis of case-control studies. Next, by means of an in silico approach, we used experimental knowledge of protein-protein interactions to evaluate the top ranked genes shared by both concepts, previously found through text mining. The meta-analysis did not show a significant pooled OR (1.11, 95% CI: 0.98 to 1.24 in Caucasians, in spite of the fact that four of the included studies had a significant OR > 1 and none of them a significant OR < 1. In contrast, the in silico approach retrieved nonrandomly shared genes by both concepts (P = 0.02, which additionally encode truly interacting proteins. The network of proteins encoded by APP, ICAM-1, ITGB2, ITGAL, SELP, SELL, IL2, IL1B, CD4, and CD8A linked immune to neurodegenerative processes and highlighted the potential roles in AD pathogenesis of endothelial regulation, infectious diseases, specific antigen presentation, and HLA-A2 in maintaining synapses.

  13. A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD.

    Science.gov (United States)

    Davidsen, Peter K; Herbert, John M; Antczak, Philipp; Clarke, Kim; Ferrer, Elisabet; Peinado, Victor I; Gonzalez, Constancio; Roca, Josep; Egginton, Stuart; Barberá, Joan A; Falciani, Francesco

    2014-01-01

    A relatively large percentage of patients with chronic obstructive pulmonary disease (COPD) develop systemic co-morbidities that affect prognosis, among which muscle wasting is particularly debilitating. Despite significant research effort, the pathophysiology of this important extrapulmonary manifestation is still unclear. A key question that remains unanswered is to what extent systemic inflammatory mediators might play a role in this pathology. Cigarette smoke (CS) is the main risk factor for developing COPD and therefore animal models chronically exposed to CS have been proposed for mechanistic studies and biomarker discovery. Although mice have been successfully used as a pre-clinical in vivo model to study the pulmonary effects of acute and chronic CS exposure, data suggest that they may be inadequate models for studying the effects of CS on peripheral muscle function. In contrast, recent findings indicate that the guinea pig model (Cavia porcellus) may better mimic muscle wasting. We have used a systems biology approach to compare the transcriptional profile of hindlimb skeletal muscles from a Guinea pig rodent model exposed to CS and/or chronic hypoxia to COPD patients with muscle wasting. We show that guinea pigs exposed to long-term CS accurately reflect most of the transcriptional changes observed in dysfunctional limb muscle of severe COPD patients when compared to matched controls. Using network inference, we could then show that the expression profile in whole lung of genes encoding for soluble inflammatory mediators is informative of the molecular state of skeletal muscles in the guinea pig smoking model. Finally, we show that CXCL10 and CXCL9, two of the candidate systemic cytokines identified using this pre-clinical model, are indeed detected at significantly higher levels in serum of COPD patients, and that their serum protein level is inversely correlated with the expression of aerobic energy metabolism genes in skeletal muscle. We conclude that

  14. 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...

  15. 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

  16. 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.

  17. 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 ...

  18. A mechanistic approach to link biological effects of radioactive substances from molecules to populations in wildlife species - A mechanistic approach to link biological effects of radionuclides from molecules to populations in wildlife species

    Energy Technology Data Exchange (ETDEWEB)

    Alonzo, Frederic; Parisot, Florian; Plaire, Delphine; Adam-Guillermin, Christelle; Garnier- Laplace, Jacqueline [Institut de Radioprotection et de Surete Nucleaire (IRSN), PRP-ENV, SERIS, LECO, Cadarache, Saint-Paul- Lez-Durance, 13115 (France)

    2014-07-01

    Understanding how toxic contaminants affect wildlife species at various levels of biological organisation (sub-cellular, histological, physiological, organism, population levels) is a major research goal in both ecotoxicology and radioecology. A mechanistic understanding of the links between the different observed perturbations is necessary to predict consequences for survival, growth and reproduction which are critical for population dynamics. However, time scales at which such links are established in the laboratory are rarely relevant for natural populations. With a small size and short life cycle, the cladoceran micro-crustacean Daphnia magna is a particularly suitable biological model for studying effects of radioactive contaminants over several generations. Multi-generational exposures are much more representative of the environmental context of field populations for which contaminations can last for durations which largely exceed individual longevity and involve exposure of many successive generations. Over the last decade, multi-generational investigations of toxic effects were conducted under controlled conditions in D. magna exposed to various radionuclides including depleted uranium, americium-241 and cesium-137, representing respectively a dominantly chemo-toxic metal, an alpha internal contamination and a gamma external radiation. Results showed in all cases that toxic effects on physiology and life history (survival, body size, fecundity) increased in severity across generations. These observations demonstrated that measured effects in one generation might not be representative of toxicity in the following offspring generations, and ultimately of the population response. Reduction in somatic growth and reproduction induced by uranium were analysed using the mechanistic modelling approach known as DEBtox (model of dynamic energy budget applied to toxicology). Modelling results suggested that uranium primarily affects assimilation. This metabolic mode

  19. The Compositional HJ-Biplot—A New Approach to Identifying the Links among Bioactive Compounds of Tomatoes

    Directory of Open Access Journals (Sweden)

    Marcos Hernández Suárez

    2016-11-01

    Full Text Available Tomatoes have been described as a functional food because of their particular composition of different bioactive compounds. In this study, the proximate composition, minerals and trace elements, and antioxidant compounds were determined in two tomato cultivars (Mariana and Dunkan that were grown in Gran Canaria (Spain either conventionally or hydroponically. Although compositional data of this type require being subjected to the specific statistical techniques of compositional analysis, this approach has not usually been considered in this context. In the present case, a compositional Mann–Whitney U test of the data showed significant differences for each factor (cultivar and cultivation system in several of the compositional variables studied. For the differences between cultivars, these parameters were the protein, Mg, lycopene, ascorbic acid, citric acid, and fumaric acid contents. For the differences between cultivation systems, they were mainly those of the mineral and trace elements group. Although one-year data are insufficient to make clear relationship among compounds because more repetitions in several localities and years are necessary, the compositional HJ-biplot (in which the links provide estimates of the linear relationship among variables results agreed with other scientific results about linear relationship among some compounds analyzed.

  20. Linking dissolution to disintegration in immediate release tablets using image analysis and a population balance modelling approach.

    Science.gov (United States)

    Wilson, David; Wren, Stephen; Reynolds, Gavin

    2012-01-01

    In order to achieve an improved understanding of disintegration and dissolution phenomena for an immediate release tablet formulation, a technique to monitor the number and size of particles entrained within the dissolution media was developed in combination with a population balancing model. Tablets were first characterized for crushing force, disintegration time and dissolution performance using standard USP methodologies. The performance of the tablets was then assessed using a new measurement system which links a "QicPic" particle imaging device to a USP dissolution vessel. This system enables us to measure the number and size of particles generated during tablet dissolution. The population balance mathematical model allowed a tablet erosion rate to be manipulated to fit the experimental data. Results showed that tablets with differing crushing forces showed different dissolution behaviors that could be explained by differing rates of particle release into the dissolution media. These behaviors were then successfully modeled to provide a description of the dissolution and disintegration behavior of the tablets in terms of a tablet erosion rate. A new approach was developed that allowed the description of the dissolution behaviors of the tablets in terms of the rate that they release particles into solution. This was then successfully modeled in terms of a tablet erosion rate.

  1. Rolling Deck to Repository (R2R): A "Linked Data" Approach for the U.S. Academic Research Fleet

    Science.gov (United States)

    Arko, R. A.; Chandler, C. L.; Clark, P. D.; Milan, A.; Mize, J.

    2011-12-01

    The U.S. academic research fleet is an essential mobile observing platform for ocean science. The NSF-funded Rolling Deck to Repository (R2R) program is working with the fleet community to routinely document, assess, and preserve data from the underway sensor systems on each vessel. The R2R facility maintains a master catalog of vessels, instrument systems, operating institutions, cruises, personnel, and data sets. In less than two years, the catalog has grown to over 2,000 cruises including unique identifiers for vessel deployments, project titles, chief scientists, dates, ports, survey targets, and navigation tracks. This master catalog is of great value to peer data systems, ranging from large national data centers to small disciplinary data offices, as an aid in organizing, extending, and quality controlling their own collections and finding related data from authoritative sources. R2R breaks with the tradition of stovepipe portals built around complex search interfaces tightly bound to backend databases. Instead, we have adopted a Linked Data approach to publish our catalog content, based on the W3C Resource Description Framework (RDF) and Uniform Resource Identifiers (URIs). Our data model is published as a collection of W3C Simple Knowledge Organization System (SKOS) concepts, mapped to partner vocabularies such as those developed by the Global Change Master Directory (GCMD) and the pan-European SeaDataNet partnership, and our catalog content is published as collections of RDF resources with globally unique and persistent identifiers. The combination of exposing our data model, mapping local terms to community-wide vocabularies, and using reliable identifiers improves interoperability and reduces ambiguity. R2R's metric of success is the degree to which peer data systems routinely harvest and reuse our content. R2R is working collaboratively with the NOAA National Data Centers and the NSF-funded Biological and Chemical Oceanography Data Management Office

  2. Rolling Deck to Repository (R2R): A "Linked Data" Approach for the U.S. Academic Research Fleet

    Science.gov (United States)

    Arko, R.; Chandler, C.; Clark, P.; Milan, A.; Mize, J.

    2012-04-01

    The Rolling Deck to Repository (R2R; http://rvdata.us/) program is developing infrastructure to routinely document, assess, and preserve the underway sensor data from U.S. academic research vessels. The R2R master catalog of vessels, instrument systems, operating institutions, cruises, personnel, data sets, event logs, and field reports has grown to over 2,200 cruises in less than two years, and is now accessible via Web services. This catalog is of great value to peer data systems, ranging from large inter/national data centers to small disciplinary data offices, as an aid in quality controlling their own collections and finding related data from authoritative sources. R2R breaks with the tradition of stovepipe portals built around complex search interfaces tightly bound to backend databases. Instead, we have adopted a Linked Data approach to publish our catalog content, based on the W3C Resource Description Framework (RDF) and Uniform Resource Identifiers (URIs). Our data model is published as a collection of W3C Simple Knowledge Organization System (SKOS) concepts, mapped to partner vocabularies such as those developed by the Global Change Master Directory (GCMD) and the pan-European SeaDataNet partnership, and our catalog content is published as collections of RDF resources with globally unique and persistent identifiers. The combination of exposing our data model, mapping local terms to community-wide vocabularies, and using reliable identifiers improves interoperability and reduces ambiguity. R2R's metric of success is the degree to which peer data systems harvest and reuse our content. R2R is working collaboratively with the NOAA National Data Centers and the NSF-funded Biological and Chemical Oceanography Data Management Office (BCO-DMO) on a range of Linked Data pilot applications, including production of ISO-compliant metadata and deployment of a RDF Query Language (SPARQL) interface. Our objective is to support a distributed, loosely federated network of

  3. Applying an ecosystem service approach to unravel links between ecosystems and society in the coast of central Chile.

    Science.gov (United States)

    de Juan, Silvia; Gelcich, Stefan; Ospina-Alvarez, Andres; Perez-Matus, Alejandro; Fernandez, Miriam

    2015-11-15

    Ecosystem-based management implies understanding feedbacks between ecosystems and society. Such understanding can be approached with the Drivers-Pressures-State change-Impacts-Response framework (DPSIR), incorporating stakeholders' preferences for ecosystem services to assess impacts on society. This framework was adapted to six locations in the central coast of Chile, where artisanal fisheries coexist with an increasing influx of tourists, and a set of fisheries management areas alternate with open access areas and a no-take Marine Protected Area (MPA). The ecosystem services in the study area were quantified using biomass and species richness in intertidal and subtidal areas as biological indicators. The demand for ecosystem services was elicited by interviews to the principal groups of users. Our results evidenced decreasing landings and a negative perception of fishermen on temporal trends of catches. The occurrence of recreational fishing was negligible, although the consumption of seafood by tourists was relatively high. Nevertheless, the consumption of organisms associated to the study system was low, which could be linked, amongst other factors, to decreasing catches. The comparison of biological indicators between management regimens provided variable results, but a positive effect of management areas and the MPA on some of the metrics was observed. The prioritising of ecosystem attributes by tourists was highly homogenous across the six locations, with "scenic beauty" consistently selected as the preferred attribute, followed by "diversity". The DPSIR framework illustrated the complex interactions existing in these locations, with weak linkages between society's priorities, existing management objectives and the state of biological communities. Overall, this work improved our knowledge on relations between components of coastal areas in central Chile, of paramount importance to advance towards an ecosystem-based management in the area. Copyright © 2015

  4. A Discovery-Based Hydrochlorination of Carvone Utilizing a Guided-Inquiry Approach to Determine the Product Structure from [superscript 13]C NMR Spectra

    Science.gov (United States)

    Pelter, Michael W.; Walker, Natalie M.

    2012-01-01

    This experiment describes a discovery-based method for the regio- and stereoselective hydrochlorination of carvone, appropriate for a 3-h second-semester organic chemistry laboratory. The product is identified through interpretation of the [superscript 13]C NMR and DEPT spectra are obtained on an Anasazi EFT-60 at 15 MHz as neat samples. A…

  5. Asymptotic Performance Analysis of the k-th Best Link Selection over Wireless Fading Channels: An Extreme Value Theory Approach

    KAUST Repository

    Al-Badarneh, Yazan Hussein

    2018-01-25

    We consider a general selection-diversity (SD) scheme in which the k-th best link is selected from a number of links. We use extreme value theory (EVT) to derive simple closed-form asymptotic expressions for the average throughput, effective throughput and average bit error probability (BEP) for the k-th best link over various channel models that are widely used to characterize fading in wireless communication systems. As an application example, we consider the Weibull fading channel model and verify the accuracy of the derived asymptotic expressions through Monte Carlo simulations.

  6. Asymptotic Performance Analysis of the k-th Best Link Selection over Wireless Fading Channels: An Extreme Value Theory Approach

    KAUST Repository

    Al-Badarneh, Yazan Hussein; Georghiades, Costas; Alouini, Mohamed-Slim

    2018-01-01

    We consider a general selection-diversity (SD) scheme in which the k-th best link is selected from a number of links. We use extreme value theory (EVT) to derive simple closed-form asymptotic expressions for the average throughput, effective throughput and average bit error probability (BEP) for the k-th best link over various channel models that are widely used to characterize fading in wireless communication systems. As an application example, we consider the Weibull fading channel model and verify the accuracy of the derived asymptotic expressions through Monte Carlo simulations.

  7. Accounting for discovery bias in genomic prediction

    Science.gov (United States)

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

  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. 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 ...

  10. 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.

  11. 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).

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

    Science.gov (United States)

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

    2015-05-15

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

  13. 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...

  14. 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

  15. 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)

  16. Using the realist perspective to link theory from qualitative evidence synthesis to quantitative studies: broadening the matrix approach.

    NARCIS (Netherlands)

    Grootel, L. van; Wesel, F. van; O'Mara-Eves, A.; Thomas, J.; Hox, J.; Boeije, H.

    2017-01-01

    Background: This study describes an approach for the use of a specific type of qualitative evidence synthesis in the matrix approach, a mixed studies reviewing method. The matrix approach compares quantitative and qualitative data on the review level by juxtaposing concrete recommendations from the

  17. Linking an Artery to the Circulation : Introducing a Quasi-Simultaneous Coupling Approach for Partitioned Systems in Hemodynamics

    NARCIS (Netherlands)

    Rozema, G.; Maurits, N. M.; Veldman, A. E. P.; VanderSloten, J; Verdonck, P; Nyssen, M; Haueisen, J

    2009-01-01

    When modeling complex systems such as the cardiovascular circulation one often needs to separate the problem into smaller subproblems because of the heterogeneous nature of the system and/or the modeling techniques. The application at hand is to link blood flow in an artery to that in the

  18. Using the Women's Community Education Approach to Deliver Community Employment Training: A Case Study from Longford Women's Link

    Science.gov (United States)

    Patterson, Lorne; Dowd, Kathleen

    2010-01-01

    The recent economic downturn and surge in unemployment has focused attention on education and training as a strategic response to Ireland's socio-economic crisis. However, that attention has been concentrated on training through statutory institutions, particularly FAS and the VECs. Longford Women's Link, a Women's Community Education centre in Co…

  19. Relational Regulation Theory : A New Approach to Explain the Link Between Perceived Social Support and Mental Health

    NARCIS (Netherlands)

    Lakey, Brian; Orehek, Edward

    Perceived support is consistently linked to good mental health, which is typically explained as resulting from objectively supportive actions that buffer stress. Yet this explanation has difficulty accounting for the often-observed main effects between support and mental health. Relational

  20. 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....

  1. Translation of the New World: intercultural dialogue or confrontation of cultures? Approach to a vision of the Other in the discovery and the Conquest chronicles

    Directory of Open Access Journals (Sweden)

    Iwona Kasperska

    2012-01-01

    Full Text Available The objective of this paper is to show main difficulties in the intercultural translation process which has been taking place during the Discovery and the Conquest of the New World, in the 15th and 16th centuries. These historical facts are considered as a metaphor of translation in general, and letters, chronicles and histories of some Spanish authors of that period are analyzed as examples of interpretation / translation based on their eurocentric and Christian background. Finally, domestication of the New Spain culture is indicated as a main translation strategy and a confrontation of cultures rather than dialogue is stressed as a general feature of the cultural contact.

  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. Does the Magnitude of the Link between Unemployment and Crime Depend on the Crime Level? A Quantile Regression Approach

    Directory of Open Access Journals (Sweden)

    Horst Entorf

    2015-07-01

    Full Text Available Two alternative hypotheses – referred to as opportunity- and stigma-based behavior – suggest that the magnitude of the link between unemployment and crime also depends on preexisting local crime levels. In order to analyze conjectured nonlinearities between both variables, we use quantile regressions applied to German district panel data. While both conventional OLS and quantile regressions confirm the positive link between unemployment and crime for property crimes, results for assault differ with respect to the method of estimation. Whereas conventional mean regressions do not show any significant effect (which would confirm the usual result found for violent crimes in the literature, quantile regression reveals that size and importance of the relationship are conditional on the crime rate. The partial effect is significantly positive for moderately low and median quantiles of local assault rates.

  4. Modelling and simulating decision processes of linked lives: An approach based on concurrent processes and stochastic race.

    Science.gov (United States)

    Warnke, Tom; Reinhardt, Oliver; Klabunde, Anna; Willekens, Frans; Uhrmacher, Adelinde M

    2017-10-01

    Individuals' decision processes play a central role in understanding modern migration phenomena and other demographic processes. Their integration into agent-based computational demography depends largely on suitable support by a modelling language. We are developing the Modelling Language for Linked Lives (ML3) to describe the diverse decision processes of linked lives succinctly in continuous time. The context of individuals is modelled by networks the individual is part of, such as family ties and other social networks. Central concepts, such as behaviour conditional on agent attributes, age-dependent behaviour, and stochastic waiting times, are tightly integrated in the language. Thereby, alternative decisions are modelled by concurrent processes that compete by stochastic race. Using a migration model, we demonstrate how this allows for compact description of complex decisions, here based on the Theory of Planned Behaviour. We describe the challenges for the simulation algorithm posed by stochastic race between multiple concurrent complex decisions.

  5. Linking Science and Language Arts: A Review of the Literature Which Compares Integrated versus Non-Integrated Approaches

    Science.gov (United States)

    Bradbury, Leslie U.

    2014-01-01

    The purpose of this paper is to review the literature published during the last 20 years that investigates the impact of approaches that describe themselves as integrating science and language arts on student learning and/or attitude at the elementary level. The majority of papers report that integrated approaches led to greater student…

  6. Using the realist perspective to link theory from qualitative evidence synthesis to quantitative studies: Broadening the matrix approach.

    Science.gov (United States)

    van Grootel, Leonie; van Wesel, Floryt; O'Mara-Eves, Alison; Thomas, James; Hox, Joop; Boeije, Hennie

    2017-09-01

    This study describes an approach for the use of a specific type of qualitative evidence synthesis in the matrix approach, a mixed studies reviewing method. The matrix approach compares quantitative and qualitative data on the review level by juxtaposing concrete recommendations from the qualitative evidence synthesis against interventions in primary quantitative studies. However, types of qualitative evidence syntheses that are associated with theory building generate theoretical models instead of recommendations. Therefore, the output from these types of qualitative evidence syntheses cannot directly be used for the matrix approach but requires transformation. This approach allows for the transformation of these types of output. The approach enables the inference of moderation effects instead of direct effects from the theoretical model developed in a qualitative evidence synthesis. Recommendations for practice are formulated on the basis of interactional relations inferred from the qualitative evidence synthesis. In doing so, we apply the realist perspective to model variables from the qualitative evidence synthesis according to the context-mechanism-outcome configuration. A worked example shows that it is possible to identify recommendations from a theory-building qualitative evidence synthesis using the realist perspective. We created subsets of the interventions from primary quantitative studies based on whether they matched the recommendations or not and compared the weighted mean effect sizes of the subsets. The comparison shows a slight difference in effect sizes between the groups of studies. The study concludes that the approach enhances the applicability of the matrix approach. Copyright © 2017 John Wiley & Sons, Ltd.

  7. [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.

  8. Payload Mass Identification of a Single-Link Flexible Arm Moving under Gravity: An Algebraic Identification Approach

    Directory of Open Access Journals (Sweden)

    Juan Carlos Cambera

    2015-01-01

    Full Text Available We deal with the online identification of the payload mass carried by a single-link flexible arm that moves on a vertical plane and therefore is affected by the gravity force. Specifically, we follow a frequency domain design methodology to develop an algebraic identifier. This identifier is capable of achieving robust and efficient mass estimates even in the presence of sensor noise. In order to highlight its performance, the proposed estimator is experimentally tested and compared with other classical methods in several situations that resemble the most typical operation of a manipulator.

  9. 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.

  10. Combinatorial materials synthesis and high-throughput screening: an integrated materials chip approach to mapping phase diagrams and discovery and optimization of functional materials.

    Science.gov (United States)

    Xiang, X D

    Combinatorial materials synthesis methods and high-throughput evaluation techniques have been developed to accelerate the process of materials discovery and optimization and phase-diagram mapping. Analogous to integrated circuit chips, integrated materials chips containing thousands of discrete different compositions or continuous phase diagrams, often in the form of high-quality epitaxial thin films, can be fabricated and screened for interesting properties. Microspot x-ray method, various optical measurement techniques, and a novel evanescent microwave microscope have been used to characterize the structural, optical, magnetic, and electrical properties of samples on the materials chips. These techniques are routinely used to discover/optimize and map phase diagrams of ferroelectric, dielectric, optical, magnetic, and superconducting materials.

  11. Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: A template-based approach-Part 2

    Energy Technology Data Exchange (ETDEWEB)

    Labroli, Marc; Paruch, Kamil; Dwyer, Michael P.; Alvarez, Carmen; Keertikar, Kartik; Poker, Cory; Rossman, Randall; Duca, Jose S.; Fischmann, Thierry O.; Madison, Vincent; Parry, David; Davis, Nicole; Seghezzi, Wolfgang; Wiswell, Derek; Guzi, Timothy J. [Merck

    2013-11-20

    Previous efforts by our group have established pyrazolo[1,5-a]pyrimidine as a viable core for the development of potent and selective CDK inhibitors. As part of an effort to utilize the pyrazolo[1,5-a]pyrimidine core as a template for the design and synthesis of potent and selective kinase inhibitors, we focused on a key regulator in the cell cycle progression, CHK1. Continued SAR development of the pyrazolo[1,5-a]pyrimidine core at the C5 and C6 positions, in conjunction with previously disclosed SAR at the C3 and C7 positions, led to the discovery of potent and selective CHK1 inhibitors.

  12. Repertoires of emotion regulation: A person-centered approach to assessing emotion regulation strategies and links to psychopathology.

    Science.gov (United States)

    Dixon-Gordon, Katherine L; Aldao, Amelia; De Los Reyes, Andres

    2015-01-01

    Despite growing research on emotion regulation (ER) strategies and psychopathology, research has primarily focused on identifying one-to-one associations between ER strategies and symptoms. Thus, little is known about how patterns in the repertoires of ER strategies are associated with different mental disorders. We utilised latent class analysis to identify distinct repertoires of ER strategies, and their links with various psychopathology domains (i.e., anxiety, depression, disordered eating, borderline personality). Participants (N = 531) reported on their use of seven ER strategies in six recalled stressful contexts, as well as on their symptoms of psychopathology. We identified five classes of ER strategies: Low Regulators (n = 168), High Regulators (n = 140), Adaptive Regulators (n = 99), Worriers/Ruminators (n = 96) and Avoiders (n = 28). Generally, High Regulators and Worriers/Ruminators endorsed greater levels of psychopathology, relative to Low and Adaptive Regulators. Our findings underscore the importance of characterising the dynamics of ER repertoires when seeking to understand links between ER strategies and psychopathology.

  13. Biomolecular bases of the senescence process and cancer. A new approach to oncological treatment linked to ageing.

    Science.gov (United States)

    Badiola, Iker; Santaolalla, Francisco; Garcia-Gallastegui, Patricia; Ana, Sánchez-Del Rey; Unda, Fernando; Ibarretxe, Gaskon

    2015-09-01

    Human ageing is associated with a gradual decline in the physiological functions of the body at multiple levels and it is a key risk factor for many diseases, including cancer. Ageing process is intimately related to widespread cellular senescence, characterised by an irreversible loss of proliferative capacity and altered functioning associated with telomere attrition, accumulation of DNA damage and compromised mitochondrial and metabolic function. Tumour and senescent cells may be generated in response to the same stimuli, where either cellular senescence or transformation would constitute two opposite outcomes of the same degenerative process. This paper aims to review the state of knowledge on the biomolecular relationship between cellular senescence, ageing and cancer. Importantly, many of the cell signalling pathways that are found to be altered during both cellular senescence and tumourigenesis are regulated through shared epigenetic mechanisms and, therefore, they are potentially reversible. MicroRNAs are emerging as pivotal players linking ageing and cancer. These small RNA molecules have generated great interest from the point of view of future clinical therapy for cancer because successful experimental results have been obtained in animal models. Micro-RNA therapies for cancer are already being tested in clinical phase trials. These findings have potential importance in cancer treatment in aged people although further research-based knowledge is needed to convert them into an effective molecular therapies for cancer linked to ageing. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. 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...

  15. A task analysis-linked approach for integrating the human factor in reliability assessments of nuclear power plants

    International Nuclear Information System (INIS)

    Ryan, T.G.

    1988-01-01

    This paper describes an emerging Task Analysis-Linked Evaluation Technique (TALENT) for assessing the contributions of human error to nuclear power plant systems unreliability and risk. Techniques such as TALENT are emerging as a recognition that human error is a primary contributor to plant safety, however, it has been a peripheral consideration to data in plant reliability evaluations. TALENT also recognizes that involvement of persons with behavioral science expertise is required to support plant reliability and risk analyses. A number of state-of-knowledge human reliability analysis tools are also discussed which support the TALENT process. The core of TALENT is comprised of task, timeline and interface analysis data which provide the technology base for event and fault tree development, serve as criteria for selecting and evaluating performance shaping factors, and which provide a basis for auditing TALENT results. Finally, programs and case studies used to refine the TALENT process are described along with future research needs in the area. (author)

  16. A General Approach to the Non-Invasive Imaging of Transgenes Using Cis-Linked Herpes Simplex Virus Thymidine Kinase

    Directory of Open Access Journals (Sweden)

    Juri G. Tjuvajev

    1999-10-01

    Full Text Available Non-invasive imaging of gene expression opens new prospects for the study of transgenic animals and the implementation of genetically based therapies in patients. We have sought to establish a general paradigm to enable whole body non-invasive imaging of any transgene. We show that the expression and imaging of HSV1-tk (a marker gene can be used to monitor the expression of the LacZ gene (a second gene under the transcriptional control of a single promoter within a bicistronic unit that includes a type II internal ribosomal entry site. In cells bearing a single copy of the vector, the expression of the two genes is proportional and constant, both in vitro and in vivo. We demonstrate that non-invasive imaging of HSV1-tk gene accurately reflects the topology and activity of the other cis-linked transgene.

  17. Strengthening the Link between Theory and Practice in Teaching Design Engineering: An Empirical Study on a New Approach

    Science.gov (United States)

    Tempelman, E.; Pilot, A.

    2011-01-01

    In 2007, the Faculty of Industrial Design Engineering of the Delft University of Technology introduced a new bachelor program. Based on theories of learning and instruction three design principles were used to develop an approach that aims to make it easier for students to bridge the gap between theoretical design engineering courses and practical…

  18. Competency-Based Approaches: Linking Theory and Practice in Professional Education with Particular Reference to Health Education

    Science.gov (United States)

    Gonczi, Andrew

    2013-01-01

    Paul Hager and I worked on a large number of research projects and publications throughout the 1990s. The focus of this work was on developing a competency-based approach to professional education and assessment. I review this work and its impact over the years. Notwithstanding the fact that most professional associations today have a competency…

  19. Applying genetics in inflammatory disease drug discovery

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  20. 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

  1. 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...

  2. 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.

  3. 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

  4. Linking urbanization to the Biological Condition Gradient (BCG) for stream ecosystems in the Northeastern United States using a Bayesian network approach

    Science.gov (United States)

    Kashuba, Roxolana; McMahon, Gerard; Cuffney, Thomas F.; Qian, Song; Reckhow, Kenneth; Gerritsen, Jeroen; Davies, Susan

    2012-01-01

    Urban development alters important physical, chemical, and biological processes that define urban stream ecosystems. An approach was developed for quantifying the effects of these processes on aquatic biota, and then linking those effects to endpoints that can be used for environmental management. These complex, interacting systems are challenging to model from a scientific standpoint. A desirable model clearly shows the system, simulates the interactions, and ultimately predicts results of management actions. Traditional regression techniques that calculate empirical relations between pairs of environmental factors do not capture the interconnected web of multiple stressors, but urban development effects are not yet understood at the detailed scales required to make mechanistic modeling approaches feasible. Therefore, in contrast to a fully deterministic or fully statistical modeling approach, a Bayesian network model provides a hybrid approach that can be used to represent known general associations between variables while acknowledging uncertainty in predicted outcomes. It does so by quantifying an expert-elicited network of probabilistic relations between variables. Advantages of this modeling approach include (1) flexibility in accommodating many model specifications and information types; (2) efficiency in storing and manipulating complex information, and to parameterize; and (3) transparency in describing the relations using nodes and arrows and in describing uncertainties with discrete probability distributions for each variable.

  5. A Link between Nano- and Classical Thermodynamics: Dissipation Analysis (The Entropy Generation Approach in Nano-Thermodynamics

    Directory of Open Access Journals (Sweden)

    Umberto Lucia

    2015-03-01

    Full Text Available The interest in designing nanosystems is continuously growing. Engineers apply a great number of optimization methods to design macroscopic systems. If these methods could be introduced into the design of small systems, a great improvement in nanotechnologies could be achieved. To do so, however, it is necessary to extend classical thermodynamic analysis to small systems, but irreversibility is also present in small systems, as the Loschmidt paradox highlighted. Here, the use of the recent improvement of the Gouy-Stodola theorem to complex systems (GSGL approach, based on the use of entropy generation, is suggested to obtain the extension of classical thermodynamics to nanothermodynamics. The result is a new approach to nanosystems which avoids the difficulties highlighted in the usual analysis of the small systems, such as the definition of temperature for nanosystems.

  6. Sex determination using free fetal DNA in early pregnancy: With the approach to sex linked recessive disorders

    Directory of Open Access Journals (Sweden)

    Amir Monfaredan

    2017-03-01

    Full Text Available Introduction: Prenatal diagnosis is testing for detection of diseases or conditions in a fetus or embryo before it is born. Most of prenatal diagnostic (PD techniques are invasive and done in late stages of pregnancy. Using fetal DNA in maternal blood for fetal sex determination in early pregnancy might help in management of X-linked genetic diseases. This study aimed to investigate the accuracy of sex determination using fetal DNA in maternal blood at 8-12 weeks of gestation. Methods: In this cross-sectional study, 30 pregnant women at 8-12 weeks of gestation were enrolled. The sex-determining region Y (SRY gene expression with the internal control (IC glyceraldehyde 3-phosphate dehydrogenase (GAPDH was investigated with quantitative real-time polymerase chain reaction (PCR using specific primers and probes. Results: Accuracy of sex determination with SRY gene expression in 8-12 weeks of pregnancy were 85%, 85%, 90% and 100% respectively. Conclusion: It seems that fetal sex determining using fetal DNA in maternal blood is a reliable method for early stage of pregnancy.

  7. "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…

  8. Astrobiology, discovery, and societal impact

    CERN Document Server

    Dick, Steven J

    2018-01-01

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

  9. 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

  10. Towards a dynamic assessment of raw materials criticality: Linking agent-based demand — With material flow supply modelling approaches

    International Nuclear Information System (INIS)

    Knoeri, Christof; Wäger, Patrick A.; Stamp, Anna; Althaus, Hans-Joerg; Weil, Marcel

    2013-01-01

    Emerging technologies such as information and communication-, photovoltaic- or battery technologies are expected to increase significantly the demand for scarce metals in the near future. The recently developed methods to evaluate the criticality of mineral raw materials typically provide a ‘snapshot’ of the criticality of a certain material at one point in time by using static indicators both for supply risk and for the impacts of supply restrictions. While allowing for insights into the mechanisms behind the criticality of raw materials, these methods cannot account for dynamic changes in products and/or activities over time. In this paper we propose a conceptual framework intended to overcome these limitations by including the dynamic interactions between different possible demand and supply configurations. The framework integrates an agent-based behaviour model, where demand emerges from individual agent decisions and interaction, into a dynamic material flow model, representing the materials' stocks and flows. Within the framework, the environmental implications of substitution decisions are evaluated by applying life-cycle assessment methodology. The approach makes a first step towards a dynamic criticality assessment and will enhance the understanding of industrial substitution decisions and environmental implications related to critical metals. We discuss the potential and limitation of such an approach in contrast to state-of-the-art methods and how it might lead to criticality assessments tailored to the specific circumstances of single industrial sectors or individual companies. - Highlights: ► Current criticality assessment methods provide a ‘snapshot’ at one point in time. ► They do not account for dynamic interactions between demand and supply. ► We propose a conceptual framework to overcomes these limitations. ► The framework integrates an agent-based behaviour model with a dynamic material flow model. ► The approach proposed makes

  11. Regional Approach for Linking Ecosystem Services and Livelihood Strategies Under Climate Change of Pastoral Communities in the Mongolian Steppe Ecosystem

    Science.gov (United States)

    Ojima, D. S.; Galvin, K.; Togtohyn, C.

    2012-12-01

    Dramatic changes due to climate and land use dynamics in the Mongolian Plateau affecting ecosystem services and agro-pastoral systems in Mongolia. Recently, market forces and development strategies are affecting land and water resources of the pastoral communities which are being further stressed due to climatic changes. Evaluation of pastoral systems, where humans depend on livestock and grassland ecosystem services, have demonstrated the vulnerability of the social-ecological system to climate change. Current social-ecological changes in ecosystem services are affecting land productivity and carrying capacity, land-atmosphere interactions, water resources, and livelihood strategies. The general trend involves greater intensification of resource exploitation at the expense of traditional patterns of extensive range utilization. Thus we expect climate-land use-land cover relationships to be crucially modified by the social-economic forces. The analysis incorporates information about the social-economic transitions taking place in the region which affect land-use, food security, and ecosystem dynamics. The region of study extends from the Mongolian plateau in Mongolia. Our research indicate that sustainability of pastoral systems in the region needs to integrate the impact of climate change on ecosystem services with socio-economic changes shaping the livelihood strategies of pastoral systems in the region. Adaptation strategies which incorporate integrated analysis of landscape management and livelihood strategies provides a framework which links ecosystem services to critical resource assets. Analysis of the available livelihood assets provides insights to the adaptive capacity of various agents in a region or in a community. Sustainable development pathways which enable the development of these adaptive capacity elements will lead to more effective adaptive management strategies for pastoral land use and herder's living standards. Pastoralists will have the

  12. Cost-utility analysis of antiviral use under pandemic influenza using a novel approach - linking pharmacology, epidemiology and heath economics.

    Science.gov (United States)

    Wu, D B C; Chaiyakunapruk, N; Pratoomsoot, C; Lee, K K C; Chong, H Y; Nelson, R E; Smith, P F; Kirkpatrick, C M; Kamal, M A; Nieforth, K; Dall, G; Toovey, S; Kong, D C M; Kamauu, A; Rayner, C R

    2018-03-01

    Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients' quality of life. Integrating PK/PD-EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.

  13. Specificity in mediated pathways by anxiety symptoms linking adolescent stress profiles to depressive symptoms: Results of a moderated mediation approach.

    Science.gov (United States)

    Anyan, Frederick; Bizumic, Boris; Hjemdal, Odin

    2018-03-01

    We investigated the specificity in mediated pathways that separately link specific stress dimensions through anxiety to depressive symptoms and the protective utility of resilience. Thus, this study goes beyond lumping together potential mediating and moderating processes that can explain the relations between stress and (symptoms of) psychopathology and the buffering effect of resilience. Ghanaian adolescents between 13 and 17 years (female = 285; male = 244) completed the Adolescent Stress Questionnaire (ASQ), Spielberger State Anxiety Inventory (STAI), Short Mood Feeling Questionnaire (SMFQ) and the Resilience Scale for Adolescents (READ). Independent samples t-test, multivariate analysis of covariance with follow-up tests and moderated mediation analyses were performed. Evidences were found for specificity in the associations between dimensions of adolescent stressors and depressive symptoms independent of transient anxiety. Transient anxiety partly accounted for the indirect effects of eight stress dimensions on depressive symptoms. Except stress of school attendance and school/leisure conflict, resilience moderated the indirect effects of specific stress dimensions on depressive symptoms. Results suggested differences in how Ghanaian adolescents view the various stress dimensions, and mediated pathways associated with anxiety and depressive symptoms. Use of cross-sectional data does not show causal process and temporal changes over time. Findings support and clarify the specificity in the interrelations and mediated pathways among dimensions of adolescent stress, transient anxiety, and depressive symptoms. Conditional process analyses shows that resilience does not only buffer direct, but also indirect psychological adversities. Interventions for good mental health may focus on low resilience subgroups in specific stress dimensions while minimizing transient anxiety. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Towards a dynamic assessment of raw materials criticality: linking agent-based demand--with material flow supply modelling approaches.

    Science.gov (United States)

    Knoeri, Christof; Wäger, Patrick A; Stamp, Anna; Althaus, Hans-Joerg; Weil, Marcel

    2013-09-01

    Emerging technologies such as information and communication-, photovoltaic- or battery technologies are expected to increase significantly the demand for scarce metals in the near future. The recently developed methods to evaluate the criticality of mineral raw materials typically provide a 'snapshot' of the criticality of a certain material at one point in time by using static indicators both for supply risk and for the impacts of supply restrictions. While allowing for insights into the mechanisms behind the criticality of raw materials, these methods cannot account for dynamic changes in products and/or activities over time. In this paper we propose a conceptual framework intended to overcome these limitations by including the dynamic interactions between different possible demand and supply configurations. The framework integrates an agent-based behaviour model, where demand emerges from individual agent decisions and interaction, into a dynamic material flow model, representing the materials' stocks and flows. Within the framework, the environmental implications of substitution decisions are evaluated by applying life-cycle assessment methodology. The approach makes a first step towards a dynamic criticality assessment and will enhance the understanding of industrial substitution decisions and environmental implications related to critical metals. We discuss the potential and limitation of such an approach in contrast to state-of-the-art methods and how it might lead to criticality assessments tailored to the specific circumstances of single industrial sectors or individual companies. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Complex Riccati equations as a link between different approaches for the description of dissipative and irreversible systems

    International Nuclear Information System (INIS)

    Schuch, Dieter

    2012-01-01

    Quantum mechanics is essentially described in terms of complex quantities like wave functions. The interesting point is that phase and amplitude of the complex wave function are not independent of each other, but coupled by some kind of conservation law. This coupling exists in time-independent quantum mechanics and has a counterpart in its time-dependent form. It can be traced back to a reformulation of quantum mechanics in terms of nonlinear real Ermakov equations or equivalent complex nonlinear Riccati equations, where the quadratic term in the latter equation explains the origin of the phase-amplitude coupling. Since realistic physical systems are always in contact with some kind of environment this aspect is also taken into account. In this context, different approaches for describing open quantum systems, particularly effective ones, are discussed and compared. Certain kinds of nonlinear modifications of the Schrödinger equation are discussed as well as their interrelations and their relations to linear approaches via non-unitary transformations. The modifications of the aforementioned Ermakov and Riccati equations when environmental effects are included can be determined in the time-dependent case. From formal similarities conclusions can be drawn how the equations of time-independent quantum mechanics can be modified to also incluce the enviromental aspects.

  16. Geometrical size effect in high cycle fatigue strength of heavy-walled Ductile Cast Iron GJS400: Weakest link vs. defect-based approach

    Directory of Open Access Journals (Sweden)

    Cova Matteo

    2014-06-01

    Full Text Available Fatigue strength is known to decrease with increasing dimension of the component. This is due to a technological size effect, related to the production process, and to a geometrical size effect, due to a higher probability of finding a large defect. To investigate the latter, an heavy-walled component made of Ductile Cast Iron (DCI has been trepanned and a fatigue test plan has been carried out using 4 different specimen geometries. An attempt has been made to relate the resulting fatigue strength using a weakest-link approach based on the effective volumes and surfaces. This approach seems to work well only in cases of different specimen's lengths. Some of the fracture surfaces were analyzed by means of SEM and the initiating defects were identified and measured. An approach in which the defects population can be randomly distributed in the specimen has been tried. Virtual fatigue tests have been carried out by considering pure propagation of the worst defect. The resulting fatigue curves showed that this approach is promising but needs further description of the initiation phase.

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Peipei Wu

    2018-02-01

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

  19. Linking process and structure in the friction stir scribe joining of dissimilar materials: A computational approach with experimental support

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Varun; Upadhyay, Piyush; Fifield, Leonard S.; Roosendaal, Timothy; Sun, Xin; Nelaturu, Phalgun; Carlson, Blair

    2018-04-01

    The friction stir welding (FSW) is a popular technique to join dissimilar materials in numerous applications. The solid state nature of the process enables joining materials with strikingly different physical properties. For the welds in lap configuration, an enhancement to this technology is made by introducing a short hard insert, referred to as cutting-scribe, at the bottom of the tool pin. The cutting-scribe induces deformation in the bottom plate which leads to the formation of mechanical interlocks or hook like structures at the interface of two materials. A thermo-mechanically coupled computational model employing coupled Eulerian-Lagrangian approach is developed to quantitatively capture the morphology of these interlocks during the FSW process. The simulations using developed model are validated by the experimental observations.The identified interface morphology coupled with the predicted temperature field from this process-structure model can then be used to estimate the post-weld microstructure and joint strength.

  20. 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.

  1. 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

  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. 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...

  4. The RiverFish Approach to Business Process Modeling: Linking Business Steps to Control-Flow Patterns

    Science.gov (United States)

    Zuliane, Devanir; Oikawa, Marcio K.; Malkowski, Simon; Alcazar, José Perez; Ferreira, João Eduardo

    Despite the recent advances in the area of Business Process Management (BPM), today’s business processes have largely been implemented without clearly defined conceptual modeling. This results in growing difficulties for identification, maintenance, and reuse of rules, processes, and control-flow patterns. To mitigate these problems in future implementations, we propose a new approach to business process modeling using conceptual schemas, which represent hierarchies of concepts for rules and processes shared among collaborating information systems. This methodology bridges the gap between conceptual model description and identification of actual control-flow patterns for workflow implementation. We identify modeling guidelines that are characterized by clear phase separation, step-by-step execution, and process building through diagrams and tables. The separation of business process modeling in seven mutually exclusive phases clearly delimits information technology from business expertise. The sequential execution of these phases leads to the step-by-step creation of complex control-flow graphs. The process model is refined through intuitive table and diagram generation in each phase. Not only does the rigorous application of our modeling framework minimize the impact of rule and process changes, but it also facilitates the identification and maintenance of control-flow patterns in BPM-based information system architectures.

  5. Modeling of Coastal Effluent Transport: an Approach to Linking of Far-field and Near-field Models

    International Nuclear Information System (INIS)

    Yang, Zhaoqing; Khangaonkar, Tarang P.

    2008-01-01

    One of the challenges in effluent transport modeling in coastal tidal environments is the proper calculation of initial dilution in connection with the far-field transport model. In this study, an approach of external linkage of far-field and near-field effluent transport models is presented, and applied to simulate the effluent transport in the Port Angeles Harbor, Washington in the Strait of Juan de Fuca. A near-field plume model was used to calculate the effluent initial dilution and a three-dimensional (3-D) hydrodynamic model was developed to simulate the tidal circulation and far-field effluent transport in the Port Angeles Harbor. In the present study, the hydrodynamic model was driven by tides and surface winds. Observed water surface elevation and velocity data were used to calibrate the model over a period covering the neap-spring tidal cycle. The model was also validated with observed surface drogue trajectory data. The model successfully reproduced the tidal dynamics in the study area and good agreements between model results and observed data were obtained. This study demonstrated that the linkage between the near-field and far-field models in effluent transport modeling can be achieved through iteratively adjusting the model grid sizes such that the far-field modeled dilution ratio and effluent concentration in the effluent discharge model grid cell match the concentration calculated by the near-field plume model

  6. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Deodutta Roy

    2015-10-01

    Full Text Available We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs, bisphenols (BPs, and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors.

  7. The future of monitoring in clinical research - a holistic approach: linking risk-based monitoring with quality management principles.

    Science.gov (United States)

    Ansmann, Eva B; Hecht, Arthur; Henn, Doris K; Leptien, Sabine; Stelzer, Hans Günther

    2013-01-01

    Since several years risk-based monitoring is the new "magic bullet" for improvement in clinical research. Lots of authors in clinical research ranging from industry and academia to authorities are keen on demonstrating better monitoring-efficiency by reducing monitoring visits, monitoring time on site, monitoring costs and so on, always arguing with the use of risk-based monitoring principles. Mostly forgotten is the fact, that the use of risk-based monitoring is only adequate if all mandatory prerequisites at site and for the monitor and the sponsor are fulfilled.Based on the relevant chapter in ICH GCP (International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use - Good Clinical Practice) this publication takes a holistic approach by identifying and describing the requirements for future monitoring and the use of risk-based monitoring. As the authors are operational managers as well as QA (Quality Assurance) experts, both aspects are represented to come up with efficient and qualitative ways of future monitoring according to ICH GCP.

  8. A “Forward Genomics” Approach Links Genotype to Phenotype using Independent Phenotypic Losses among Related Species

    Directory of Open Access Journals (Sweden)

    Michael Hiller

    2012-10-01

    Full Text Available Genotype-phenotype mapping is hampered by countless genomic changes between species. We introduce a computational “forward genomics” strategy that—given only an independently lost phenotype and whole genomes—matches genomic and phenotypic loss patterns to associate specific genomic regions with this phenotype. We conducted genome-wide screens for two metabolic phenotypes. First, our approach correctly matches the inactivated Gulo gene exactly with the species that lost the ability to synthesize vitamin C. Second, we attribute naturally low biliary phospholipid levels in guinea pigs and horses to the inactivated phospholipid transporter Abcb4. Human ABCB4 mutations also result in low phospholipid levels but lead to severe liver disease, suggesting compensatory mechanisms in guinea pig and horse. Our simulation studies, counts of independent changes in existing phenotype surveys, and the forthcoming availability of many new genomes all suggest that forward genomics can be applied to many phenotypes, including those relevant for human evolution and disease.

  9. 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

  10. Fateful discovery almost forgotten

    CERN Multimedia

    1989-01-01

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

  11. 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.

  12. Linked functional network abnormalities during intrinsic and extrinsic activity in schizophrenia as revealed by a data-fusion approach.

    Science.gov (United States)

    Hashimoto, Ryu-Ichiro; Itahashi, Takashi; Okada, Rieko; Hasegawa, Sayaka; Tani, Masayuki; Kato, Nobumasa; Mimura, Masaru

    2018-01-01

    Abnormalities in functional brain networks in schizophrenia have been studied by examining intrinsic and extrinsic brain activity under various experimental paradigms. However, the identified patterns of abnormal functional connectivity (FC) vary depending on the adopted paradigms. Thus, it is unclear whether and how these patterns are inter-related. In order to assess relationships between abnormal patterns of FC during intrinsic activity and those during extrinsic activity, we adopted a data-fusion approach and applied partial least square (PLS) analyses to FC datasets from 25 patients with chronic schizophrenia and 25 age- and sex-matched normal controls. For the input to the PLS analyses, we generated a pair of FC maps during the resting state (REST) and the auditory deviance response (ADR) from each participant using the common seed region in the left middle temporal gyrus, which is a focus of activity associated with auditory verbal hallucinations (AVHs). PLS correlation (PLS-C) analysis revealed that patients with schizophrenia have significantly lower loadings of a component containing positive FCs in default-mode network regions during REST and a component containing positive FCs in the auditory and attention-related networks during ADR. Specifically, loadings of the REST component were significantly correlated with the severities of positive symptoms and AVH in patients with schizophrenia. The co-occurrence of such altered FC patterns during REST and ADR was replicated using PLS regression, wherein FC patterns during REST are modeled to predict patterns during ADR. These findings provide an integrative understanding of altered FCs during intrinsic and extrinsic activity underlying core schizophrenia symptoms.

  13. Missing Links Between Genetically Inherited Molecules in Split Cord Malformation and Other Anomaly: A Bench to Bedside Approach.

    Science.gov (United States)

    Barik, Mayadhar; Mishra, Pravash R; Mohapatra, Ashok Kumar

    2018-01-01

    Split cord malformation (SCM) is associated with extensive vertebral fusions (Klippel-Feil anomaly). In light of previous embryological theories and recent research findings, we attempt to document the origin of split cord, and vertebral fusions involvement of spectrum of genes is necessary to know better the etiopathogenesis of SCM and its associated diseases. We used the various databases such as PubMed/MEDLINE, Cochrane Review, Hinari, and Google Scholar for the recently published medical literature. The women had been living and still born infants had SCM. The relative risk (RR) and possible molecular mechanism are described details of major genes and its variants in details. Although molecular genetics involvement including with recent advances of study add an evidence of both Mendelian and Non-Mendelian fashion is discussed with all genetic components. We mentioned our earlier experience and responsibility of SCM and its associated diseases. Although different mechanisms are suggested for the development of SCM observed in our experience, there is a midline lesion bisecting the neuroepithelium and the notochordal plate, which is responsible for complete splitting of the cervical cord with anterior bony defect. The localized disturbance of cervical neural tube closure accounts for SCM with partial dorsal splitting of the cord with posterior vertebral defect and associated diseases. According to the best of our knowledge, this report is the first one to be documented by wider spectrum of variants from (experimental studies to human subject). This add a complex interaction of mutant variants drive toward an additional second-hit alterations for the SCM. The up-to-date information, documented in proper order, derived the bench-to-bedside approach to overcome this burden of SCM, which is globally noticed with other additional diseases.

  14. Using an integrated approach to link biomarker responses and physiological stress to growth impairment of cadmium-exposed larval topsmelt

    International Nuclear Information System (INIS)

    Rose, Wendy L.; Nisbet, Roger M.; Green, Peter G.; Norris, Sarah; Fan, Teresa; Smith, Edmund H.; Cherr, Gary N.; Anderson, Susan L.

    2006-01-01

    In this study, we used an integrated approach to determine whether key biochemical, cellular, and physiological responses were related to growth impairment of cadmium (Cd)-exposed larval topsmelt (Atherinops affinis). Food intake (Artemia franciscana nauplii), oxygen consumption rates, apoptotic DNA fragmentation (TUNEL assay), and metallothionein (MT)-like protein levels, were separately measured in relation to growth of larval topsmelt aqueously exposed to sublethal doses of Cd for 14 days. Cadmium accumulation and concentrations of abundant metals were also evaluated in a subset of fish. Fish in the highest Cd treatments (50 and 100 ppb Cd) were smaller in final mean weight and length, and consumed fewer A. franciscana nauplii than control fish. Food intake was positively correlated with final weight of larval topsmelt in Cd and control treatments; food intake increased as final weight of the fish increased. Oxygen consumption rates were positively correlated with Cd concentration and mean oxygen consumption rates were inversely correlated with final mean weight of topsmelt; the smallest fish were found in the highest Cd treatment and were respiring at higher rates than control fish. Apoptotic DNA fragmentation was concentration-dependent and was associated with diminished growth. Apoptotic DNA fragmentation was elevated in the gill of fish exposed to 50 ppb Cd, and in the gut, gill, and liver of fish exposed to 100 ppb Cd. Metallothionein (MT)-like protein levels in fish from 100 ppb Cd treatments were significantly higher than those in other treatments. Oxygen consumption rates may have increased as a compensatory response to Cd exposure. However, it is likely that the energy produced was allocated to an increased metabolic demand due to apoptosis, MT synthesis, and changes in ion regulation. This diversion of energy expenditures could contribute to growth impairment of Cd-exposed fish

  15. 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 ...

  16. 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)

  17. 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...

  18. 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.)

  19. A Chemoinformatics Approach to the Discovery of Lead-Like Molecules from Marine and Microbial Sources En Route to Antitumor and Antibiotic Drugs

    Science.gov (United States)

    Pereira, Florbela; Latino, Diogo A. R. S.; Gaudêncio, Susana P.

    2014-01-01

    The comprehensive information of small molecules and their biological activities in the PubChem database allows chemoinformatic researchers to access and make use of large-scale biological activity data to improve the precision of drug profiling. A Quantitative Structure–Activity Relationship approach, for classification, was used for the prediction of active/inactive compounds relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1804 compounds from PubChem. Using the best classification models for antibiotic and antitumor activities a data set of marine and microbial natural products from the AntiMarin database were screened—57 and 16 new lead compounds for antibiotic and antitumor drug design were proposed, respectively. All compounds proposed by our approach are classified as non-antibiotic and non-antitumor compounds in the AntiMarin database. Recently several of the lead-like compounds proposed by us were reported as being active in the literature. PMID:24473174

  20. Reversible and Selective Encapsulation of Dextromethorphan and β-Estradiol Using an Asymmetric Molecular Capsule Assembled via the Weak-Link Approach.

    Science.gov (United States)

    Mendez-Arroyo, Jose; d'Aquino, Andrea I; Chinen, Alyssa B; Manraj, Yashin D; Mirkin, Chad A

    2017-02-01

    An allosterically regulated, asymmetric receptor featuring a binding cavity large enough to accommodate three-dimensional pharmaceutical guest molecules as opposed to planar, rigid aromatics, was synthesized via the Weak-Link Approach. This architecture is capable of switching between an expanded, flexible "open" configuration and a collapsed, rigid "closed" one. The structure of the molecular receptor can be completely modulated in situ through the use of simple ionic effectors, which reversibly control the coordination state of the Pt(II) metal hinges to open and close the molecular receptor. The substantial change in binding cavity size and electrostatic charge between the two configurations is used to explore the capture and release of two guest molecules, dextromethorphan and β-estradiol, which are widely found as pollutants in groundwater.

  1. Probablistic approach to the assessment of the long-term risk linked to the disposal of radioactive waste in geological repositories

    Energy Technology Data Exchange (ETDEWEB)

    Bertozzi, G; D' Alessandro, M [Commission of the European Communities, Ispra (Italy). Joint Research Centre

    1982-12-01

    A probabilistic approach is described for the assessment of the risk linked to the underground disposal of radioactive materials. Risk quantification is split into the assessment of radioactivity release probabilities and the corresponding consequences. Both probabilities and consequences may be quantified through the use of models which, because of unavoidable uncertainties in input data, are implemented in a probabilistic way. For any uncertain parameter a probability distribution must be defined, in order that the model results reflect the uncertainties of the input data. The probability distribution of the results can be obtained by using analytical codes as well as with Monte Carlo simulations. A simple application of the methodology is given to show what kind of information can be drawn.

  2. Investigation of a novel approach for the cross-linking characterization of SU-8 photoresist materials by means of optical dispersion measurements

    Science.gov (United States)

    Taudt, Ch.; Baselt, T.; Koch, E.; Hartmann, P.

    2014-03-01

    The increase in efficiency and precision in the production of semiconductor structures under the use of polymeric materials like SU-8 is crucial in securing the technological innovation within this industry. The manufacturing of structures on wafers demands a high quality of materials, tools and production processes. In particular, deviations in the materials' parameters (e.g. cross-linking state, density or mechanical properties) could lead to subsequent problems such as a reduced lifetime of structures and systems. In particular problems during the soft and post-exposure bake process can lead to an inhomogeneous distribution of material properties. This paper describes a novel approach for the characterization of SU-8 material properties in relation to a second epoxy-based material of different cross-linking by the measurement of optical dispersion within the material. A white-light interferometer was used. In particular the setup consisted of a white-light source, a Michelson-type interferometer and a spectrometer. The investigation of the dispersion characteristics was carried out by the detection of the equalization wavelength for different positions of the reference arm in a range from 400 to 900 nm. The measured time delay due to dispersion ranges from 850 to 1050 ps/m. For evaluation purposes a 200μm SU-8 sample was characterized in the described setup regarding its dispersion characteristics in relation to bulk epoxy material. The novel measurement approach allowed a fast and high-resolution material characterization for SU-8 micro structures which was suitable for integration in production lines. The outlook takes modifications of the experimental setup regarding on-wafer measurements into account.

  3. 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.

  4. An Unprecedented Blue Chromophore Found in Nature using a "Chemistry First" and Molecular Networking Approach: Discovery of Dactylocyanines A-H.

    Science.gov (United States)

    Bonneau, Natacha; Chen, Guanming; Lachkar, David; Boufridi, Asmaa; Gallard, Jean-François; Retailleau, Pascal; Petek, Sylvain; Debitus, Cécile; Evanno, Laurent; Beniddir, Mehdi A; Poupon, Erwan

    2017-10-17

    Guided by a "chemistry first" approach using molecular networking, eight new bright-blue colored natural compounds, namely dactylocyanines A-H (3-10), were isolated from the Polynesian marine sponge Dactylospongia metachromia. Starting from ilimaquinone (1), an hemisynthetic phishing probe (2) was prepared for annotating and matching structurally related natural substances in D. metachromia crude extract network. This strategy allowed characterizing for the first time in Nature the blue zwitterionic quinonoid chromophore. The solvatochromic properties of the latter are reported. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. About probabilistic integration of ill-posed geophysical tomography and logging data: A knowledge discovery approach versus petrophysical transfer function concepts illustrated using cross-borehole radar-, P- and S-wave traveltime tomography in combination with cone penetration and dielectric logging data

    Science.gov (United States)

    Paasche, Hendrik

    2018-01-01

    Site characterization requires detailed and ideally spatially continuous information about the subsurface. Geophysical tomographic experiments allow for spatially continuous imaging of physical parameter variations, e.g., seismic wave propagation velocities. Such physical parameters are often related to typical geotechnical or hydrological target parameters, e.g. as achieved from 1D direct push or borehole logging. Here, the probabilistic inference of 2D tip resistance, sleeve friction, and relative dielectric permittivity distributions in near-surface sediments is constrained by ill-posed cross-borehole seismic P- and S-wave and radar wave traveltime tomography. In doing so, we follow a discovery science strategy employing a fully data-driven approach capable of accounting for tomographic ambiguity and differences in spatial resolution between the geophysical tomograms and the geotechnical logging data used for calibration. We compare the outcome to results achieved employing classical hypothesis-driven approaches, i.e., deterministic transfer functions derived empirically for the inference of 2D sleeve friction from S-wave velocity tomograms and theoretically for the inference of 2D dielectric permittivity from radar wave velocity tomograms. The data-driven approach offers maximal flexibility in combination with very relaxed considerations about the character of the expected links. This makes it a versatile tool applicable to almost any combination of data sets. However, error propagation may be critical and justify thinking about a hypothesis-driven pre-selection of an optimal database going along with the risk of excluding relevant information from the analyses. Results achieved by transfer function rely on information about the nature of the link and optimal calibration settings drawn as retrospective hypothesis by other authors. Applying such transfer functions at other sites turns them into a priori valid hypothesis, which can, particularly for empirically

  6. 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)

  7. 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.

  8. 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

  9. Linking top-down and bottom-up approaches for assessing the vulnerability of a 100 % renewable energy system in Northern-Italy

    Science.gov (United States)

    Borga, Marco; Francois, Baptiste; Hingray, Benoit; Zoccatelli, Davide; Creutin, Jean-Dominique; brown, Casey

    2016-04-01

    Due to their variable and un-controllable features, integration of Variable Renewable Energies (e.g. solar-power, wind-power and hydropower, denoted as VRE) into the electricity network implies higher production variability and increased risk of not meeting demand. Two approaches are commonly used for assessing this risk and especially its evolution in a global change context (i.e. climate and societal changes); top-down and bottom-up approaches. The general idea of a top-down approach is to drive analysis of global change or of some key aspects of global change on their systems (e.g., the effects of the COP 21, of the deployment of Smart Grids, or of climate change) with chains of loosely linked simulation models within a predictive framework. The bottom-up approach aims to improve understanding of the dependencies between the vulnerability of regional systems and large-scale phenomenon from knowledge gained through detailed exploration of the response to change of the system of interest, which may reveal vulnerability thresholds, tipping points as well as potential opportunities. Brown et al. (2012) defined an analytical framework to merge these two approaches. The objective is to build, a set of Climate Response Functions (CRFs) putting in perspective i) indicators of desired states ("success") and undesired states ("failure") of a system as defined in collaboration with stakeholders 2) exhaustive exploration of the effects of uncertain forcings and imperfect system understanding on the response of the system itself to a plausible set of possible changes, implemented a with multi-dimensionally consistent "stress test" algorithm, and 3) a set "ex post" hydroclimatic and socioeconomic scenarios that provide insight into the differential effectiveness of alternative policies and serve as entry points for the provision of climate information to inform policy evaluation and choice. We adapted this approach for analyzing a 100 % renewable energy system within a region

  10. 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.

  11. 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.

  12. A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy.

    Science.gov (United States)

    Ramsden, Nicola L; Buetow, Lori; Dawson, Alice; Kemp, Lauris A; Ulaganathan, Venkatsubramanian; Brenk, Ruth; Klebe, Gerhard; Hunter, William N

    2009-04-23

    The nonmevalonate route to isoprenoid biosynthesis is essential in Gram-negative bacteria and apicomplexan parasites. The enzymes of this pathway are absent from mammals, contributing to their appeal as chemotherapeutic targets. One enzyme, 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase (IspF), has been validated as a target by genetic approaches in bacteria. Virtual screening against Escherichia coli IspF (EcIspF) was performed by combining a hierarchical filtering methodology with molecular docking. Docked compounds were inspected and 10 selected for experimental validation. A surface plasmon resonance assay was developed and two weak ligands identified. Crystal structures of EcIspF complexes were determined to support rational ligand development. Cytosine analogues and Zn(2+)-binding moieties were characterized. One of the putative Zn(2+)-binding compounds gave the lowest measured K(D) to date (1.92 +/- 0.18 muM). These data provide a framework for the development of IspF inhibitors to generate lead compounds of therapeutic potential against microbial pathogens.

  13. Recent advances in candidate-gene and whole-genome approaches to the discovery of anthelmintic resistance markers and the description of drug/receptor interactions

    Directory of Open Access Journals (Sweden)

    Andrew C. Kotze

    2014-12-01

    Full Text Available Anthelmintic resistance has a great impact on livestock production systems worldwide, is an emerging concern in companion animal medicine, and represents a threat to our ongoing ability to control human soil-transmitted helminths. The Consortium for Anthelmintic Resistance and Susceptibility (CARS provides a forum for scientists to meet and discuss the latest developments in the search for molecular markers of anthelmintic resistance. Such markers are important for detecting drug resistant worm populations, and indicating the likely impact of the resistance on drug efficacy. The molecular basis of resistance is also important for understanding how anthelmintics work, and how drug resistant populations arise. Changes to target receptors, drug efflux and other biological processes can be involved. This paper reports on the CARS group meeting held in August 2013 in Perth, Australia. The latest knowledge on the development of molecular markers for resistance to each of the principal classes of anthelmintics is reviewed. The molecular basis of resistance is best understood for the benzimidazole group of compounds, and we examine recent work to translate this knowledge into useful diagnostics for field use. We examine recent candidate-gene and whole-genome approaches to understanding anthelmintic resistance and identify markers. We also look at drug transporters in terms of providing both useful markers for resistance, as well as opportunities to overcome resistance through the targeting of the transporters themselves with inhibitors. Finally, we describe the tools available for the application of the newest high-throughput sequencing technologies to the study of anthelmintic resistance.

  14. 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

  15. A New Approach for the Discovery of Antibiotics by Targeting Non-Multiplying Bacteria: A Novel Topical Antibiotic for Staphylococcal Infections

    Science.gov (United States)

    Hu, Yanmin; Shamaei-Tousi, Alireza; Liu, Yingjun; Coates, Anthony

    2010-01-01

    In a clinical infection, multiplying and non-multiplying bacteria co-exist. Antibiotics kill multiplying bacteria, but they are very inefficient at killing non-multipliers which leads to slow or partial death of the total target population of microbes in an infected tissue. This prolongs the duration of therapy, increases the emergence of resistance and so contributes to the short life span of antibiotics after they reach the market. Targeting non-multiplying bacteria from the onset of an antibiotic development program is a new concept. This paper describes the proof of principle for this concept, which has resulted in the development of the first antibiotic using this approach. The antibiotic, called HT61, is a small quinolone-derived compound with a molecular mass of about 400 Daltons, and is active against non-multiplying bacteria, including methicillin sensitive and resistant, as well as Panton-Valentine leukocidin-carrying Staphylococcus aureus. It also kills mupirocin resistant MRSA. The mechanism of action of the drug is depolarisation of the cell membrane and destruction of the cell wall. The speed of kill is within two hours. In comparison to the conventional antibiotics, HT61 kills non-multiplying cells more effectively, 6 logs versus less than one log for major marketed antibiotics. HT61 kills methicillin sensitive and resistant S. aureus in the murine skin bacterial colonization and infection models. No resistant phenotype was produced during 50 serial cultures over a one year period. The antibiotic caused no adverse affects after application to the skin of minipigs. Targeting non-multiplying bacteria using this method should be able to yield many new classes of antibiotic. These antibiotics may be able to reduce the rate of emergence of resistance, shorten the duration of therapy, and reduce relapse rates. PMID:20676403

  16. 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

  17. Using Stable Isotopes to Link Nutrient Sources in the Everglades and Biological Sinks in Florida Bay: A Biogeochemical Approach to Evaluate Ecosystem Response to Changing Nutrient Regimes

    Science.gov (United States)

    Hoare, A. M.; Hollander, D. J.; Heil, C.; Glibert, P.; Murasko, S.; Revilla, M.; Alexander, J.

    2005-05-01

    Anthropogenic influences in South Florida have led to deterioration of its two major ecosystems, the Everglades wetlands and the Florida Bay estuary. Consequently, the Comprehensive Everglades Restoration Plan has been proposed to restore the Everglades ecosystem; however, restoration efforts will likely exert new ecological changes in the Everglades and ultimately Florida Bay. The success of the Florida Everglades restoration depends on our understanding and ability to predict how regional changes in the distribution and composition of dissolved organic and inorganic nutrients will direct the downstream biogeochemical dynamics of Florida Bay. While the transport of freshwater and nutrients to Florida Bay have been studied, much work remains to directly link nutrient dynamics in Florida Bay to nutrient sources in the Everglades. Our study uses stable C and N isotopic measurements of chemical and biological materials from the Everglades and Florida Bay as part of a multi-proxy approach to link nutrient sources in the Everglades to biological sinks in Florida Bay. Isotopic analyses of dissolved and particulate species of water, aquatic vegetation and sedimentary organic matter show that the watersheds within the Everglades are chemically distinct and that these signatures are also reflected in the bay. A large east-west gradient in both carbon and nitrogen (as much as 10‰ for δ15N POM) reflect differing nutrient sources for each region of Florida Bay and is strongly correlated with upstream sources in the Everglades. Isotopic signatures also reflect seasonal relationships associated with wet and dry periods. High C and N measurements of DOM and POM measurements suggest significant influence from waste water in Canal C-111 in eastern Florida Bay, particularly during the dry season. These observations show that nutrients from the Everglades watersheds enter Florida Bay and are important in controlling biogeochemical processes in the bay. This study proves that

  18. Comment on "drug discovery: turning the titanic".

    Science.gov (United States)

    Lesterhuis, W Joost; Bosco, Anthony; Lake, Richard A

    2014-03-26

    The pathobiology-based approach to research and development has been the dominant paradigm for successful drug discovery over the last decades. We propose that the molecular and cellular events that govern a resolving, rather than an evolving, disease may reveal new druggable pathways.

  19. 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.

  20. Discovery Learning: Zombie, Phoenix, or Elephant?

    Science.gov (United States)

    Bakker, Arthur

    2018-01-01

    Discovery learning continues to be a topic of heated debate. It has been called a zombie, and this special issue raises the question whether it may be a phoenix arising from the ashes to which the topic was burnt. However, in this commentary I propose it is more like an elephant--a huge topic approached by many people who address different…

  1. Computer-Assisted Discovery and Proof

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, David H.; Borwein, Jonathan M.

    2007-12-10

    With the advent of powerful, widely-available mathematical software, combined with ever-faster computer hardware, we are approaching a day when both the discovery and proof of mathematical facts can be done in a computer-assisted manner. his article presents several specific examples of this new paradigm in action.

  2. 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.

  3. 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.

  4. 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.

  5. The Discovery of Insulin: A Case Study of Scientific Methodology

    Science.gov (United States)

    Stansfield, William D.

    2012-01-01

    The nature of scientific research sometimes involves a trial-and-error procedure. Popular reviews of successful results from this approach often sanitize the story by omitting unsuccessful trials, thus painting the rosy impression that research simply follows a direct route from hypothesis to experiment to scientific discovery. The discovery of…

  6. Discovery: Pile Patterns

    Science.gov (United States)

    de Mestre, Neville

    2017-01-01

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

  7. 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 ...

  8. Discovery of TUG-770

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  9. The discovery of fission

    International Nuclear Information System (INIS)

    McKay, H.A.C.

    1978-01-01

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

  10. The Discovery of America

    Science.gov (United States)

    Martin, Paul S.

    1973-01-01

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

  11. 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.

  12. Safety and Efficacy of Epithelium-On Corneal Collagen Cross-Linking Using a Multifactorial Approach to Achieve Proper Stromal Riboflavin Saturation

    Directory of Open Access Journals (Sweden)

    Aleksandar Stojanovic

    2012-01-01

    Full Text Available Purpose. To evaluate the efficacy and safety of epithelium-on corneal collagen cross-linking (CXL using a multifactorial approach to achieve proper stromal riboflavin saturation. Methods. This non-randomized retrospective study comprised 61 eyes with progressive keratoconus treated with epithelium-on CXL. Chemical epithelial penetration enhancement (benzalkonium chloride-containing local medication and hypotonic riboflavin solution, mechanical disruption of the superficial epithelium, and prolongation of the riboflavin-induction time until verification of stromal saturation were used before the UVA irradiation. Uncorrected and corrected distance visual acuity (UDVA, CDVA, refraction, corneal topography, and aberrometry were evaluated at baseline and at 1, 3, 6, and 12 months postoperative. Results. At 12-month, UDVA and CDVA improved significantly. None of the eyes lost lines of CDVA, while 27.4% of the eyes gained 2 or more lines. Mean spherical equivalent decreased by 0.74 D, and mean cylindrical reduction was 1.15 D. Irregularity index and asymmetry from Scheimpflug-based topography and Max-K at the location of cone from Placido-based topography showed a significant decrease. Higher-order-aberration data demonstrated a slight reduction in odd-order aberrations S 3, 5,7 (=0.04. Postoperative pain without other complications was recorded. Conclusion. Epithelium-on CXL with our novel protocol appeared to be safe and effective in the treatment of progressive keratoconus.

  13. Social media for message testing: a multilevel approach to linking favorable viewer responses with message, producer, and viewer influence on YouTube.

    Science.gov (United States)

    Paek, Hye-Jin; Hove, Thomas; Jeon, Jehoon

    2013-01-01

    To explore the feasibility of social media for message testing, this study connects favorable viewer responses to antismoking videos on YouTube with the videos' message characteristics (message sensation value [MSV] and appeals), producer types, and viewer influences (viewer rating and number of viewers). Through multilevel modeling, a content analysis of 7,561 viewer comments on antismoking videos is linked with a content analysis of 87 antismoking videos. Based on a cognitive response approach, viewer comments are classified and coded as message-oriented thought, video feature-relevant thought, and audience-generated thought. The three mixed logit models indicate that videos with a greater number of viewers consistently increased the odds of favorable viewer responses, while those presenting humor appeals decreased the odds of favorable message-oriented and audience-generated thoughts. Some significant interaction effects show that videos produced by laypeople may hinder favorable viewer responses, while a greater number of viewer comments can work jointly with videos presenting threat appeals to predict favorable viewer responses. Also, for a more accurate understanding of audience responses to the messages, nuance cues should be considered together with message features and viewer influences.

  14. Exploring nomological link between automated service quality, customer satisfaction and behavioural intentions with CRM performance indexing approach: Empirical evidence from Indian banking industry

    Directory of Open Access Journals (Sweden)

    Arup Kumar Baksi

    2013-01-01

    Full Text Available Automation in service delivery has increased the consumers’ expectation with regard to service quality and subsequently the perception of the same. Technology-driven services redefined quality dimensions and their subsequent impact on the behavioural outcomes of the consumers with specific reference to attitudinal loyalty and propensity to switch. Customer Relationship Management (CRM has further reinforced the operational aspects of a service provider by integrating the behavioural perspectives with technology. This paper attempts to explore the nomological link between automated service quality and its behavioural consequences with specific reference to consumers’ attitudinal loyalty and their intention to switch or defect from their present service provider. The study further takes into consideration the moderating effects of the performance of the dimensions and attributes of customer relationship management by introducing a novel approach to CRM performance indexing. The cross-sectional study was carried out with the customers of State Bank of India at Asansol, Durgapur, Bolpur and Santiniketan in West Bengal, India. The study used structural equation modeling (SEM to assess and validate the nomological relationship between the variables.

  15. Astroparticle physics: puzzles and discoveries

    International Nuclear Information System (INIS)

    Berezinsky, V

    2008-01-01

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

  16. Thought for food (safety) in the EU: a discourse-analytical approach

    NARCIS (Netherlands)

    Paul, K.T.

    2008-01-01

    This paper seeks to explain the development of a transnational food safety policy approach in the context of the European Union (EU). The diverse reactions to the series of food scares over the past decade, such as the discovery of the link between BSE (Bovine Spongiform Encephalopathy) and the

  17. 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.

  18. Link layer topology discovery in an uncooperative ethernet environment

    CSIR Research Space (South Africa)

    Delport, JP

    2007-05-01

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

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

    Science.gov (United States)

    Cox, Simon; Schade, Sven

    2010-05-01

    'Linked Data' is a current buzz-phrase promoting access to various forms of data on the internet. It starts from the two principles that have underpinned the architecture and scalability of the World Wide Web: 1. Universal Resource Identifiers - using the http protocol which is supported by the DNS system. 2. Hypertext - in which URIs of related resources are embedded within a document. Browsing is the key mode of interaction, with traversal of links between resources under control of the client. Linked Data also adds, or re-emphasizes: • Content negotiation - whereby the client uses http headers to tell the service what representation of a resource is acceptable, • Semantic Web principles - formal semantics for links, following the RDF data model and encoding, and • The 'mashup' effect - in which original and unexpected value may emerge from reuse of data, even if published in raw or unpolished form. Linked Data promotes typed links to all kinds of data, so is where the semantic web meets the 'deep web', i.e. resources which may be accessed using web protocols, but are in representations not indexed by search engines. Earth sciences are data rich, but with a strong legacy of specialized formats managed and processed by disconnected applications. However, most contemporary research problems require a cross-disciplinary approach, in which the heterogeneity resulting from that legacy is a significant challenge. In this context, Linked Data clearly has much to offer the earth sciences. But, there are some important questions to answer. What is a resource? Most earth science data is organized in arrays and databases. A subset useful for a particular study is usually identified by a parameterized query. The Linked Data paradigm emerged from the world of documents, and will often only resolve data-sets. It is impractical to create even nested navigation resources containing links to all potentially useful objects or subsets. From the viewpoint of human user

  20. 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.

  1. 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

  2. Atlas of Astronomical Discoveries

    CERN Document Server

    Schilling, Govert

    2011-01-01

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

  3. Fateful discovery almost forgotten

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

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

  4. 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.

  5. Evaluation of hybrid theoretical approaches for structural determination of a glycine-linked cisplatin derivative via infrared multiple photon dissociation (IRMPD) action spectroscopy

    NARCIS (Netherlands)

    He, C.C.; Kimutai, B.; Bao, X.; Hamlow, L.; Zhu, Y.; Strobehn, S.F.; Gao, J.; Berden, G.; Oomens, J.; Chow, C.S.; Rodgers, M.T.

    2015-01-01

    To gain a better understanding of the binding mechanism and assist in the optimization of chemical probing and drug design applications, experimental and theoretical studies of a series of amino acid-linked cisplatin derivatives are being pursued. Glyplatin (glycine-linked cisplatin) was chosen for

  6. Changes in the Metabolome of Picea balfouriana Embryogenic Tissues That Were Linked to Different Levels of 6-BAP by Gas Chromatography-Mass Spectrometry Approach.

    Directory of Open Access Journals (Sweden)

    Q F Li

    Full Text Available Embryogenic cultures of Picea balfouriana, which is an important commercial species for reforestation in Southern China, easily lose their embryogenic ability during long-term culture. Embryogenic tissue that proliferated at lower concentrations (3.6 μM and 2.5 μM of 6-benzylaminopurine (6-BAP were more productive, and generated 113 ± 6 and 89 ± 3 mature embryos per 100 mg embryogenic tissue, respectively. A metabolomic approach was used to study the changes in metabolites linked to embryogenic competence related to three different 6-BAP concentrations (2.5 μM, 3.6 μM, and 5 μM. A total of 309 compounds were obtained, among which 123 metabolites mapped to Kyoto Encyclopedia of Genes and genomes (KEGG pathways. The levels of 35 metabolites were significantly differentially regulated among the three 6-BAP treatments, and 32 metabolites differed between the 2.5 μM and 5 μM treatments. A total of 17 metabolites appeared only once among the three comparisons. The combination of a score plot and a loading plot showed that in the samples with higher embryogenic ability (3.6 μM and 2.5 μM, up-regulated metabolites were mostly amino acids and down-regulated metabolites were mostly primary carbohydrates (especially sugars. These results suggested that 6-BAP may influence embryogenic competence by nitrogen metabolism, which could cause an increase in amino acid levels and higher amounts of aspartate, isoleucine, and leucine in tissues with higher embryogenic ability. Furthermore, we speculated that 6-BAP may affect the amount of tryptophan in tissues, which would change the indole-3-acetic acid levels and influence the embryogenic ability.

  7. Operative Links

    DEFF Research Database (Denmark)

    Wistoft, Karen; Højlund, Holger

    2012-01-01

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

  8. 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.

  9. 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...

  10. Scandinavian links

    DEFF Research Database (Denmark)

    Matthiessen, Christian Wichmann; Knowles, Richard D.

    2014-01-01

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

  11. Links between circadian rhythms and psychiatric disease

    Directory of Open Access Journals (Sweden)

    Ilia N Karatsoreos

    2014-05-01

    Full Text Available Determining the cause of psychiatric disorders is a goal of modern neuroscience, and will hopefully lead to the discovery of treatments to either prevent or alleviate the suffering caused by these diseases. One roadblock to attaining this goal is the realization that neuropsychiatric diseases are rarely due to a single gene polymorphism, environmental exposure, or developmental insult. Rather, it is a complex interaction between these various influences that likely leads to the development of clinically relevant syndromes. Our lab is exploring the links between environmental exposures and neurobehavioral function by investigating how disruption of the circadian (daily clock alters the structure and function of neural circuits, with the hypothesis that disrupting this crucial homeostatic system can directly contribute to altered vulnerability of the organism to other factors that interact to produce psychiatric illness. This review explores some historical and more recent findings that link disrupted circadian clocks to neuropsychiatric disorders, particularly depression, mania, and schizophrenia. We take a comparative approach by exploring the effects observed in human populations, as well as some experimental models used in the laboratory to unravel mechanistic and causal relationships between disruption of the circadian clock and behavioral abnormalities. This is a rich area of research that we predict will contribute greatly to our understanding of how genes, environment, and development interact to modulate an individual’s vulnerability to psychiatric disorders.

  12. 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 ...

  13. An Even Better Approach : Improving the B.A.T.M.A.N. Protocol Through Formal Modelling and Analysis

    NARCIS (Netherlands)

    Fehnker, Ansgar; Chaudhary, Kaylash; Mehta, Vinay; Dutle, Aaron; Muñoz, César; Narkawicz, Anthony

    2018-01-01

    This paper considers a network routing protocol known as Better Approach to Mobile Adhoc Networks (B.A.T.M.A.N.). The protocol has two aims: first, discovery of all bidirectional links, and second, identification of the best-next-hop to the other nodes. A key mechanism of the protocol is to flood

  14. 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.

  15. 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.

  16. 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.

  17. Causality discovery technology

    Science.gov (United States)

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

    2012-11-01

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

  18. Automated Supernova Discovery (Abstract)

    Science.gov (United States)

    Post, R. S.

    2015-12-01

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

  19. 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:

  20. 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…

  1. 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.

  2. Discovery and preclinical development of new antibiotics.

    Science.gov (United States)

    Hughes, Diarmaid; Karlén, Anders

    2014-05-01

    Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted.

  3. Systems biology and biomarker discovery

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.

    2010-12-01

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

  4. 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...

  5. Hippocampus discovery First steps

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

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

  6. A systematic approach for the assessment of bacterial growth-controlling factors linked to biological stability of drinking water in distribution systems

    KAUST Repository

    Prest, E. I.; Hammes, F.; Kotzsch, S.; van Loosdrecht, M. C. M.; Vrouwenvelder, Johannes S.

    2016-01-01

    A systematic approach is presented for the assessment of (i) bacterial growth-controlling factors in drinking water and (ii) the impact of distribution conditions on the extent of bacterial growth in full-scale distribution systems. The approach

  7. Inseparability of science history and discovery

    Directory of Open Access Journals (Sweden)

    J. M. Herndon

    2010-04-01

    Full Text Available Science is very much a logical progression through time. Progressing along a logical path of discovery is rather like following a path through the wilderness. Occasionally the path splits, presenting a choice; the correct logical interpretation leads to further progress, the wrong choice leads to confusion. By considering deeply the relevant science history, one might begin to recognize past faltering in the logical progression of observations and ideas and, perhaps then, to discover new, more precise understanding. The following specific examples of science faltering are described from a historical perspective: (1 Composition of the Earth's inner core; (2 Giant planet internal energy production; (3 Physical impossibility of Earth-core convection and Earth-mantle convection, and; (4 Thermonuclear ignition of stars. For each example, a revised logical progression is described, leading, respectively, to: (1 Understanding the endo-Earth's composition; (2 The concept of nuclear georeactor origin of geo- and planetary magnetic fields; (3 The invalidation and replacement of plate tectonics; and, (4 Understanding the basis for the observed distribution of luminous stars in galaxies. These revised logical progressions clearly show the inseparability of science history and discovery. A different and more fundamental approach to making scientific discoveries than the frequently discussed variants of the scientific method is this: An individual ponders and through tedious efforts arranges seemingly unrelated observations into a logical sequence in the mind so that causal relationships become evident and new understanding emerges, showing the path for new observations, for new experiments, for new theoretical considerations, and for new discoveries. Science history is rich in "seemingly unrelated observations" just waiting to be logically and causally related to reveal new discoveries.

  8. Chemical cross-linking with thiol-cleavable reagents combined with differential mass spectrometric peptide mapping--a novel approach to assess intermolecular protein contacts

    DEFF Research Database (Denmark)

    Bennett, K L; Kussmann, M; Björk, P

    2000-01-01

    The intermolecular contact regions between monomers of the homodimeric DNA binding protein ParR and the interaction between the glycoproteins CD28 and CD80 were investigated using a strategy that combined chemical cross-linking with differential MALDI-MS analyses. ParR dimers were modified in vit...

  9. "Learning to Do" as a Pillar of Education and Its Links to Entrepreneurial Studies in Higher Education: European Contexts and Approaches

    Science.gov (United States)

    Miclea, Mircea

    2004-01-01

    The author links the "learning to do" pillar, one of the four pillars of the Delors Report of 1996 , "Learning: The Treasure Within", to the principles and purposes of an entrepreneurial university and the aims of the European Commission and the Bologna Process to enhance the employability of graduates of higher education. An entrepreneurial…

  10. A PRACTICAL APPROACH TO THE DETECTION OF ANDROGEN RECEPTOR GENE-MUTATIONS AND PEDIGREE ANALYSIS IN FAMILIES WITH X-LINKED ANDROGEN INSENSITIVITY

    NARCIS (Netherlands)

    RISSTALPERS, C; HOOGENBOEZEM, T; SLEDDENS, HFBM; VERLEUNMOOIJMAN, MCT; DEGENHART, HJ; DROP, SLS; HALLEY, DJJ; Oosterwijk, Jan; HODGINS, MB; TRAPMAN, J; BRINKMANN, AO

    Androgen insensitivity syndrome (AIS) is an X-linked disorder in which defects in the androgen receptor gene have prevented the normal development of both internal and external male structures in 46,XY individuals. This survey reports the analysis of 11 AIS subjects. The androgen receptor gene of

  11. A practical approach to the detection of androgen receptor gene mutations and pedigree analysis in families with x-linked androgen insensitivity

    NARCIS (Netherlands)

    Ris-Stalpers, C.; Hoogenboezem, T.; Sleddens, H. F.; Verleun-Mooijman, M. C.; Degenhart, H. J.; Drop, S. L.; Halley, D. J.; Oosterwijk, J. C.; Hodgins, M. B.; Trapman, J.

    1994-01-01

    Androgen insensitivity syndrome (AIS) is an X-linked disorder in which defects in the androgen receptor gene have prevented the normal development of both internal and external male structures in 46,XY individuals. This survey reports the analysis of 11 AIS subjects. The androgen receptor gene of

  12. Rule Induction-Based Knowledge Discovery for Energy Efficiency

    OpenAIRE

    Chen, Qipeng; Fan, Zhong; Kaleshi, Dritan; Armour, Simon M D

    2015-01-01

    Rule induction is a practical approach to knowledge discovery. Provided that a problem is developed, rule induction is able to return the knowledge that addresses the goal of this problem as if-then rules. The primary goals of knowledge discovery are for prediction and description. The rule format knowledge representation is easily understandable so as to enable users to make decisions. This paper presents the potential of rule induction for energy efficiency. In particular, three rule induct...

  13. 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

  14. 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

  15. 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.

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. Discovery and Selection of Semantic Web Services

    CERN Document Server

    Wang, Xia

    2013-01-01

    For advanced web search engines to be able not only to search for semantically related information dispersed over different web pages, but also for semantic services providing certain functionalities, discovering semantic services is the key issue. Addressing four problems of current solution, this book presents the following contributions. A novel service model independent of semantic service description models is proposed, which clearly defines all elements necessary for service discovery and selection. It takes service selection as its gist and improves efficiency. Corresponding selection algorithms and their implementation as components of the extended Semantically Enabled Service-oriented Architecture in the Web Service Modeling Environment are detailed. Many applications of semantic web services, e.g. discovery, composition and mediation, can benefit from a general approach for building application ontologies. With application ontologies thus built, services are discovered in the same way as with single...

  5. West Nile Virus Drug Discovery

    Directory of Open Access Journals (Sweden)

    Siew Pheng Lim

    2013-12-01

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

  6. Context discovery using attenuated Bloom codes: model description and validation

    NARCIS (Netherlands)

    Liu, F.; Heijenk, Geert

    A novel approach to performing context discovery in ad-hoc networks based on the use of attenuated Bloom filters is proposed in this report. In order to investigate the performance of this approach, a model has been developed. This document describes the model and its validation. The model has been

  7. 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...

  8. "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

  9. '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”.

  10. Scaling the walls of discovery: using semantic metadata for integrative problem solving.

    Science.gov (United States)

    Manning, Maurice; Aggarwal, Amit; Gao, Kevin; Tucker-Kellogg, Greg

    2009-03-01

    Current data integration approaches by bioinformaticians frequently involve extracting data from a wide variety of public and private data repositories, each with a unique vocabulary and schema, via scripts. These separate data sets must then be normalized through the tedious and lengthy process of resolving naming differences and collecting information into a single view. Attempts to consolidate such diverse data using data warehouses or federated queries add significant complexity and have shown limitations in flexibility. The alternative of complete semantic integration of data requires a massive, sustained effort in mapping data types and maintaining ontologies. We focused instead on creating a data architecture that leverages semantic mapping of experimental metadata, to support the rapid prototyping of scientific discovery applications with the twin goals of reducing architectural complexity while still leveraging semantic technologies to provide flexibility, efficiency and more fully characterized data relationships. A metadata ontology was developed to describe our discovery process. A metadata repository was then created by mapping metadata from existing data sources into this ontology, generating RDF triples to describe the entities. Finally an interface to the repository was designed which provided not only search and browse capabilities but complex query templates that aggregate data from both RDF and RDBMS sources. We describe how this approach (i) allows scientists to discover and link relevant data across diverse data sources and (ii) provides a platform for development of integrative informatics applications.

  11. Symptoms of cybersex addiction can be linked to both approaching and avoiding pornographic stimuli: Results from an analogue sample of regular cybersex users

    Directory of Open Access Journals (Sweden)

    Jan eSnagowski

    2015-05-01

    Full Text Available The phenomenology, classification, and diagnostic criteria of cybersex addiction are discussed controversial. Some approaches point towards similarities to substance dependencies for which approach/avoidance tendencies are crucial mechanisms. Several researchers have argued that within an addiction-related decision situation, individuals might either show tendencies to approach or avoid addiction-related stimuli. In the current study 123 heterosexual males completed an Approach-Avoidance-Task (AAT; Rinck & Becker, 2007 modified with pornographic pictures. During the AAT participants either had to push pornographic stimuli away or pull them towards themselves with a joystick. Sensitivity towards sexual excitation, problematic sexual behavior, and tendencies towards cybersex addiction were assessed with questionnaires. Results showed that individuals with tendencies towards cybersex addiction tended to either approach or avoid pornographic stimuli. Additionally, moderated regression analyses revealed that individuals with high sexual excitation and problematic sexual behavior who showed high approach/avoidance tendencies, reported higher symptoms of cybersex addiction. Analogous to substance dependencies, results suggest that both approach and avoidance tendencies might play a role in cybersex addiction. Moreover, an interaction with sensitivity towards sexual excitation and problematic sexual behavior could have an accumulating effect on the severity of subjective complaints in everyday life due to cybersex use. The findings provide further empirical evidence for similarities between cybersex addiction and substance dependencies. Such similarities could be retraced to a comparable neural processing of cybersex- and drug-related cues.

  12. Symptoms of cybersex addiction can be linked to both approaching and avoiding pornographic stimuli: results from an analog sample of regular cybersex users.

    Science.gov (United States)

    Snagowski, Jan; Brand, Matthias

    2015-01-01

    There is no consensus regarding the phenomenology, classification, and diagnostic criteria of cybersex addiction. Some approaches point toward similarities to substance dependencies for which approach/avoidance tendencies are crucial mechanisms. Several researchers have argued that within an addiction-related decision situation, individuals might either show tendencies to approach or avoid addiction-related stimuli. In the current study 123 heterosexual males completed an Approach-Avoidance-Task (AAT; Rinck and Becker, 2007) modified with pornographic pictures. During the AAT participants either had to push pornographic stimuli away or pull them toward themselves with a joystick. Sensitivity toward sexual excitation, problematic sexual behavior, and tendencies toward cybersex addiction were assessed with questionnaires. Results showed that individuals with tendencies toward cybersex addiction tended to either approach or avoid pornographic stimuli. Additionally, moderated regression analyses revealed that individuals with high sexual excitation and problematic sexual behavior who showed high approach/avoidance tendencies, reported higher symptoms of cybersex addiction. Analogous to substance dependencies, results suggest that both approach and avoidance tendencies might play a role in cybersex addiction. Moreover, an interaction with sensitivity toward sexual excitation and problematic sexual behavior could have an accumulating effect on the severity of subjective complaints in everyday life due to cybersex use. The findings provide further empirical evidence for similarities between cybersex addiction and substance dependencies. Such similarities could be retraced to a comparable neural processing of cybersex- and drug-related cues.

  13. Discovery of natural resources

    Science.gov (United States)

    Guild, P.W.

    1976-01-01

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

  14. Supernovae Discovery Efficiency

    Science.gov (United States)

    John, Colin

    2018-01-01

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

  15. Four disruptive strategies for removing drug discovery bottlenecks.

    Science.gov (United States)

    Ekins, Sean; Waller, Chris L; Bradley, Mary P; Clark, Alex M; Williams, Antony J

    2013-03-01

    Drug discovery is shifting focus from industry to outside partners and, in the process, creating new bottlenecks. Technologies like high throughput screening (HTS) have moved to a larger number of academic and institutional laboratories in the USA, with little coordination or consideration of the outputs and creating a translational gap. Although there have been collaborative public-private partnerships in Europe to share pharmaceutical data, the USA has seemingly lagged behind and this may hold it back. Sharing precompetitive data and models may accelerate discovery across the board, while finding the best collaborators, mining social media and mobile approaches to open drug discovery should be evaluated in our efforts to remove drug discovery bottlenecks. We describe four strategies to rectify the current unsustainable situation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Context-sensitive service discovery experimental prototype and evaluation

    DEFF Research Database (Denmark)

    Balken, Robin; Haukrogh, Jesper; L. Jensen, Jens

    2007-01-01

    The amount of different networks and services available to users today are increasing. This introduces the need for a way to locate and sort out irrelevant services in the process of discovering available services to a user. This paper describes and evaluates a prototype of an automated discovery...... and selection system, which locates services relevant to a user, based on his/her context and the context of the available services. The prototype includes a multi-level, hierarchical system approach and the introduction of entities called User-nodes, Super-nodes and Root-nodes. These entities separate...... the network in domains that handle the complex distributed service discovery, which is based on dynamically changing context information. In the prototype, a method for performing context-sensitive service discovery has been realised. The service discovery part utilizes UPnP, which has been expanded in order...

  17. Systems Pharmacology in Small Molecular Drug Discovery

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    2016-02-01

    Full Text Available Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity, target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

  18. Students Excited by Stellar Discovery

    Science.gov (United States)

    2011-02-01

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

  19. RAS - Screens & Assays - Drug Discovery

    Science.gov (United States)

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

  20. Discovery of the iron isotopes

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  1. Discovery of the silver isotopes

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  2. Discovery of the cadmium isotopes

    International Nuclear Information System (INIS)

    Amos, S.; Thoennessen, M.

    2010-01-01

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

  3. Discoveries of isotopes by fission

    Indian Academy of Sciences (India)

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

  4. The discovery of 'heavy light'

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

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

  5. Discovery – Development of Rituximab

    Science.gov (United States)

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

  6. 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.)

  7. 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.

  8. 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.

  9. 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

  10. Exploring a clinically friendly web-based approach to clinical decision support linked to the electronic health record: design philosophy, prototype implementation, and framework for assessment.

    Science.gov (United States)

    Miller, Perry; Phipps, Michael; Chatterjee, Sharmila; Rajeevan, Nallakkandi; Levin, Forrest; Frawley, Sandra; Tokuno, Hajime

    2014-07-01

    Computer-based clinical decision support (CDS) is an important component of the electronic health record (EHR). As an increasing amount of CDS is implemented, it will be important that this be accomplished in a fashion that assists in clinical decision making without imposing unacceptable demands and burdens upon the provider's practice. The objective of our study was to explore an approach that allows CDS to be clinician-friendly from a variety of perspectives, to build a prototype implementation that illustrates features of the approach, and to gain experience with a pilot framework for assessment. The paper first discusses the project's design philosophy and goals. It then describes a prototype implementation (Neuropath/CDS) that explores the approach in the domain of neuropathic pain and in the context of the US Veterans Administration EHR. Finally, the paper discusses a framework for assessing the approach, illustrated by a pilot assessment of Neuropath/CDS. The paper describes the operation and technical design of Neuropath/CDS, as well as the results of the pilot assessment, which emphasize the four areas of focus, scope, content, and presentation. The work to date has allowed us to explore various design and implementation issues relating to the approach illustrated in Neuropath/CDS, as well as the development and pilot application of a framework for assessment.

  11. State of the Art in Tumor Antigen and Biomarker Discovery

    International Nuclear Information System (INIS)

    Even-Desrumeaux, Klervi; Baty, Daniel; Chames, Patrick

    2011-01-01

    Our knowledge of tumor immunology has resulted in multiple approaches for the treatment of cancer. However, a gap between research of new tumors markers and development of immunotherapy has been established and very few markers exist that can be used for treatment. The challenge is now to discover new targets for active and passive immunotherapy. This review aims at describing recent advances in biomarkers and tumor antigen discovery in terms of antigen nature and localization, and is highlighting the most recent approaches used for their discovery including “omics” technology

  12. Oncology drug discovery: planning a turnaround.

    Science.gov (United States)

    Toniatti, Carlo; Jones, Philip; Graham, Hilary; Pagliara, Bruno; Draetta, Giulio

    2014-04-01

    We have made remarkable progress in our understanding of the pathophysiology of cancer. This improved understanding has resulted in increasingly effective targeted therapies that are better tolerated than conventional cytotoxic agents and even curative in some patients. Unfortunately, the success rate of drug approval has been limited, and therapeutic improvements have been marginal, with too few exceptions. In this article, we review the current approach to oncology drug discovery and development, identify areas in need of improvement, and propose strategies to improve patient outcomes. We also suggest future directions that may improve the quality of preclinical and early clinical drug evaluation, which could lead to higher approval rates of anticancer drugs.

  13. An adaptive approach to family-centered intervention in schools: linking intervention engagement to academic outcomes in middle and high school.

    Science.gov (United States)

    Stormshak, Elizabeth A; Connell, Arin; Dishion, Thomas J

    2009-09-01

    This study examined the impact of an adaptive approach to family intervention in public schools on academic outcomes from age 11 to 17. Students were randomly assigned to the three-session Family Check-Up (FCU), which is designed to motivate change in parenting practices by using an assessment-driven approach and strengths-based feedback. All services were voluntary, and approximately 25% of the families engaged in the FCU. Compared with matched controls, adolescents whose parents received the FCU maintained a satisfactory GPA into high school, and intervention engagement was associated with improved attendance. The highest-risk families were the most likely to engage in the family-centered intervention, suggesting the efficacy of integrating supportive services to families in the context of other schoolwide approaches to promote the success and achievement of vulnerable students.

  14. 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...

  15. Preparation and characterization of malonic acid cross-linked chitosan and collagen 3D scaffolds: an approach on non-covalent interactions.

    Science.gov (United States)

    Mitra, Tapas; Sailakshmi, G; Gnanamani, A; Mandal, A B

    2012-05-01

    The present study emphasizes the influence of non-covalent interactions on the mechanical and thermal properties of the scaffolds of chitosan/collagen origin. Malonic acid (MA), a bifuncitonal diacid was chosen to offer non-covalent cross-linking. Three dimensional scaffolds was prepared using chitosan at 1.0% (w/v) and MA at 0.2% (w/v), similarly collagen 0.5% (w/v) and MA 0.2% (w/v) and characterized. Results on FT-IR, TGA, DSC, SEM and mechanical properties (tensile strength, stiffness, Young's modulus, etc.) assessment demonstrated the existence of non-covalent interaction between MA and chitosan/collagen, which offered flexibility and high strength to the scaffolds suitable for tissue engineering research. Studies using NIH 3T3 fibroblast cells suggested biocompatibility nature of the scaffolds. Docking simulation study further supports the intermolecular hydrogen bonding interactions between MA and chitosan/collagen.

  16. 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.

  17. 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.

  18. 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...

  19. 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...

  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...