Sample records for link discovery approaches
-
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
-
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.
-
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.
-
Leveraging Crowdsourcing and Linked Open Data for Geoscience Data Sharing and Discovery
Narock, T. W.; Rozell, E. A.; Hitzler, P.; Arko, R. A.; Chandler, C. L.; Wilson, B. D.
2013-12-01
Data citation standards can form the basis for increased incentives, recognition, and rewards for scientists. Additionally, knowing which data were utilized in a particular publication can enhance discovery and reuse. Yet, a lack of data citation information in existing publications as well as ambiguities across datasets can limit the accuracy of automated linking approaches. We describe a crowdsourcing approach, based on Linked Open Data, in which AGU abstracts are linked to the data used in those presentations. We discuss our efforts to incentivize participants through promotion of their research, the role that the Semantic Web can play in this effort, and how this work differs from existing platforms such as Mendeley and ResearchGate. Further, we discuss the benefits and challenges of Linked Open Data as a technical solution including the role of provenance, trust, and computational reasoning.
-
SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines
Yumusak, Semih; Dogdu, Erdogan; Kodaz, Halife; Kamilaris, Andreas
2016-01-01
In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this ...
-
SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines
Yumusak, Semih; Dogdu, Erdogan; Kodaz, Halife; Kamilaris, Andreas; Vandenbussche, Pierre-Yves
In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this method, most of the currently listed SPARQL endpoints in existing endpoint repositories, as well as a significant number of new SPARQL endpoints, have been discovered. Finally, we have developed a new SPARQL endpoint crawler (SpEC) for crawling and link analysis.
-
Discovery learning with SAVI approach in geometry learning
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.
-
Proteomic and metabolomic approaches to biomarker discovery
Issaq, Haleem J
2013-01-01
Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution. The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis...
-
Knowledge-Based Topic Model for Unsupervised Object Discovery and Localization.
Niu, Zhenxing; Hua, Gang; Wang, Le; Gao, Xinbo
Unsupervised object discovery and localization is to discover some dominant object classes and localize all of object instances from a given image collection without any supervision. Previous work has attempted to tackle this problem with vanilla topic models, such as latent Dirichlet allocation (LDA). However, in those methods no prior knowledge for the given image collection is exploited to facilitate object discovery. On the other hand, the topic models used in those methods suffer from the topic coherence issue-some inferred topics do not have clear meaning, which limits the final performance of object discovery. In this paper, prior knowledge in terms of the so-called must-links are exploited from Web images on the Internet. Furthermore, a novel knowledge-based topic model, called LDA with mixture of Dirichlet trees, is proposed to incorporate the must-links into topic modeling for object discovery. In particular, to better deal with the polysemy phenomenon of visual words, the must-link is re-defined as that one must-link only constrains one or some topic(s) instead of all topics, which leads to significantly improved topic coherence. Moreover, the must-links are built and grouped with respect to specific object classes, thus the must-links in our approach are semantic-specific , which allows to more efficiently exploit discriminative prior knowledge from Web images. Extensive experiments validated the efficiency of our proposed approach on several data sets. It is shown that our method significantly improves topic coherence and outperforms the unsupervised methods for object discovery and localization. In addition, compared with discriminative methods, the naturally existing object classes in the given image collection can be subtly discovered, which makes our approach well suited for realistic applications of unsupervised object discovery.Unsupervised object discovery and localization is to discover some dominant object classes and localize all of object
-
Fragment-based approaches to the discovery of kinase inhibitors.
Mortenson, Paul N; Berdini, Valerio; O'Reilly, Marc
2014-01-01
Protein kinases are one of the most important families of drug targets, and aberrant kinase activity has been linked to a large number of disease areas. Although eminently targetable using small molecules, kinases present a number of challenges as drug targets, not least obtaining selectivity across such a large and relatively closely related target family. Fragment-based drug discovery involves screening simple, low-molecular weight compounds to generate initial hits against a target. These hits are then optimized to more potent compounds via medicinal chemistry, usually facilitated by structural biology. Here, we will present a number of recent examples of fragment-based approaches to the discovery of kinase inhibitors, detailing the construction of fragment-screening libraries, the identification and validation of fragment hits, and their optimization into potent and selective lead compounds. The advantages of fragment-based methodologies will be discussed, along with some of the challenges associated with using this route. Finally, we will present a number of key lessons derived both from our own experience running fragment screens against kinases and from a large number of published studies.
-
Hierarchical virtual screening approaches in small molecule drug discovery.
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.
-
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
-
Development of Scientific Approach Based on Discovery Learning Module
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
-
Computational neuropharmacology: dynamical approaches in drug discovery.
Aradi, Ildiko; Erdi, Péter
2006-05-01
Computational approaches that adopt dynamical models are widely accepted in basic and clinical neuroscience research as indispensable tools with which to understand normal and pathological neuronal mechanisms. Although computer-aided techniques have been used in pharmaceutical research (e.g. in structure- and ligand-based drug design), the power of dynamical models has not yet been exploited in drug discovery. We suggest that dynamical system theory and computational neuroscience--integrated with well-established, conventional molecular and electrophysiological methods--offer a broad perspective in drug discovery and in the search for novel targets and strategies for the treatment of neurological and psychiatric diseases.
-
Net present value approaches for drug discovery.
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.
-
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...
-
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.
-
Introduction to fragment-based drug discovery.
Erlanson, Daniel A
2012-01-01
Fragment-based drug discovery (FBDD) has emerged in the past decade as a powerful tool for discovering drug leads. The approach first identifies starting points: very small molecules (fragments) that are about half the size of typical drugs. These fragments are then expanded or linked together to generate drug leads. Although the origins of the technique date back some 30 years, it was only in the mid-1990s that experimental techniques became sufficiently sensitive and rapid for the concept to be become practical. Since that time, the field has exploded: FBDD has played a role in discovery of at least 18 drugs that have entered the clinic, and practitioners of FBDD can be found throughout the world in both academia and industry. Literally dozens of reviews have been published on various aspects of FBDD or on the field as a whole, as have three books (Jahnke and Erlanson, Fragment-based approaches in drug discovery, 2006; Zartler and Shapiro, Fragment-based drug discovery: a practical approach, 2008; Kuo, Fragment based drug design: tools, practical approaches, and examples, 2011). However, this chapter will assume that the reader is approaching the field with little prior knowledge. It will introduce some of the key concepts, set the stage for the chapters to follow, and demonstrate how X-ray crystallography plays a central role in fragment identification and advancement.
-
Semantic Search in E-Discovery: An Interdisciplinary Approach
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
-
CLARM: An integrative approach for functional modules discovery
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.
-
"Structured Discovery": A Modified Inquiry Approach to Teaching Social Studies.
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)
-
Applying linked data approaches to pharmacology: Architectural decisions and implementation
Gray, A.J.G; Groth, P.T.; Loizou, A.; Askjaer, S; Brenninkmeijer, C; Burger, K.; Chichester, C.; Evelo, C.T.; Goble, C.A.; Harland, L; Pettifier, S; Thompson, M.; Waagmeester, A; William, A.J
2014-01-01
The discovery of new medicines requires pharmacologists to interact with a number of information sources ranging from tabular data to scientific papers, and other specialized formats. In this application report, we describe a linked data platform for integrating multiple pharmacology datasets that
-
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
-
Discovery and Development of ATP-Competitive mTOR Inhibitors Using Computational Approaches.
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.
-
A collaborative filtering-based approach to biomedical knowledge discovery.
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
-
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...
-
A new approach to the rationale discovery of polymeric biomaterials
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
-
A novel approach to Service Discovery in Mobile Adhoc Network
Islam, Noman; Shaikh, Zubair A.
2015-01-01
Mobile Adhoc Network (MANET) is a network of a number of mobile routers and associated hosts, organized in a random fashion via wireless links. During recent years MANET has gained enormous amount of attention and has been widely used for not only military purposes but for search-and-rescue operations, intelligent transportation system, data collection, virtual classrooms and ubiquitous computing. Service Discovery is one of the most important issues in MANET. It is defined as the process of ...
-
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.
-
Network-based approaches to climate knowledge discovery
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.
-
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
-
Cloud computing approaches to accelerate drug discovery value chain.
Garg, Vibhav; Arora, Suchir; Gupta, Chitra
2011-12-01
Continued advancements in the area of technology have helped high throughput screening (HTS) evolve from a linear to parallel approach by performing system level screening. Advanced experimental methods used for HTS at various steps of drug discovery (i.e. target identification, target validation, lead identification and lead validation) can generate data of the order of terabytes. As a consequence, there is pressing need to store, manage, mine and analyze this data to identify informational tags. This need is again posing challenges to computer scientists to offer the matching hardware and software infrastructure, while managing the varying degree of desired computational power. Therefore, the potential of "On-Demand Hardware" and "Software as a Service (SAAS)" delivery mechanisms cannot be denied. This on-demand computing, largely referred to as Cloud Computing, is now transforming the drug discovery research. Also, integration of Cloud computing with parallel computing is certainly expanding its footprint in the life sciences community. The speed, efficiency and cost effectiveness have made cloud computing a 'good to have tool' for researchers, providing them significant flexibility, allowing them to focus on the 'what' of science and not the 'how'. Once reached to its maturity, Discovery-Cloud would fit best to manage drug discovery and clinical development data, generated using advanced HTS techniques, hence supporting the vision of personalized medicine.
-
A Linked Science Investigation: Enhancing Climate Change Data Discovery with Semantic Technologies.
Pouchard, Line C; Branstetter, Marcia L; Cook, Robert B; Devarakonda, Ranjeet; Green, Jim; Palanisamy, Giri; Alexander, Paul; Noy, Natalya F
2013-09-01
Linked Science is the practice of inter-connecting scientific assets by publishing, sharing and linking scientific data and processes in end-to-end loosely coupled workflows that allow the sharing and re-use of scientific data. Much of this data does not live in the cloud or on the Web, but rather in multi-institutional data centers that provide tools and add value through quality assurance, validation, curation, dissemination, and analysis of the data. In this paper, we make the case for the use of scientific scenarios in Linked Science. We propose a scenario in river-channel transport that requires biogeochemical experimental data and global climate-simulation model data from many sources. We focus on the use of ontologies-formal machine-readable descriptions of the domain-to facilitate search and discovery of this data. Mercury, developed at Oak Ridge National Laboratory, is a tool for distributed metadata harvesting, search and retrieval. Mercury currently provides uniform access to more than 100,000 metadata records; 30,000 scientists use it each month. We augmented search in Mercury with ontologies, such as the ontologies in the Semantic Web for Earth and Environmental Terminology (SWEET) collection by prototyping a component that provides access to the ontology terms from Mercury. We evaluate the coverage of SWEET for the ORNL Distributed Active Archive Center (ORNL DAAC).
-
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.
-
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...
-
A Linked Data Approach for the Discovery of Educational ICT Tools in the Web of Data
Ruiz-Calleja, Adolfo; Vega-Gorgojo, Guillermo; Asensio-Perez, Juan I.; Bote-Lorenzo, Miguel L.; Gomez-Sanchez, Eduardo; Alario-Hoyos, Carlos
2012-01-01
The use of Information and Communication Technologies (ICT) tools to support learning activities is nowadays generalized. Several educational registries provide information about ICT tools in order to help educators in their discovery and selection. These registries are typically isolated and require much effort to keep tool information up to…
-
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.
-
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.
-
Approach to cerebrospinal fluid (CSF) biomarker discovery and evaluation in HIV infection.
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.
-
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.
-
Analysis student self efficacy in terms of using Discovery Learning model with SAVI approach
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.
-
Use of machine learning approaches for novel drug discovery.
Lima, Angélica Nakagawa; Philot, Eric Allison; Trossini, Gustavo Henrique Goulart; Scott, Luis Paulo Barbour; Maltarollo, Vinícius Gonçalves; Honorio, Kathia Maria
2016-01-01
The use of computational tools in the early stages of drug development has increased in recent decades. Machine learning (ML) approaches have been of special interest, since they can be applied in several steps of the drug discovery methodology, such as prediction of target structure, prediction of biological activity of new ligands through model construction, discovery or optimization of hits, and construction of models that predict the pharmacokinetic and toxicological (ADMET) profile of compounds. This article presents an overview on some applications of ML techniques in drug design. These techniques can be employed in ligand-based drug design (LBDD) and structure-based drug design (SBDD) studies, such as similarity searches, construction of classification and/or prediction models of biological activity, prediction of secondary structures and binding sites docking and virtual screening. Successful cases have been reported in the literature, demonstrating the efficiency of ML techniques combined with traditional approaches to study medicinal chemistry problems. Some ML techniques used in drug design are: support vector machine, random forest, decision trees and artificial neural networks. Currently, an important application of ML techniques is related to the calculation of scoring functions used in docking and virtual screening assays from a consensus, combining traditional and ML techniques in order to improve the prediction of binding sites and docking solutions.
-
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.
-
Argo_CUDA: Exhaustive GPU based approach for motif discovery in large DNA datasets.
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.
-
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.
-
[Fragment-based drug discovery: concept and aim].
Tanaka, Daisuke
2010-03-01
Fragment-Based Drug Discovery (FBDD) has been recognized as a newly emerging lead discovery methodology that involves biophysical fragment screening and chemistry-driven fragment-to-lead stages. Although fragments, defined as structurally simple and small compounds (typically FBDD primarily turns our attention to weakly but specifically binding fragments (hit fragments) as the starting point of medicinal chemistry. Hit fragments are then promoted to more potent lead compounds through linking or merging with another hit fragment and/or attaching functional groups. Another positive aspect of FBDD is ligand efficiency. Ligand efficiency is a useful guide in screening hit selection and hit-to-lead phases to achieve lead-likeness. Owing to these features, a number of successful applications of FBDD to "undruggable targets" (where HTS and other lead identification methods failed to identify useful lead compounds) have been reported. As a result, FBDD is now expected to complement more conventional methodologies. This review, as an introduction of the following articles, will summarize the fundamental concepts of FBDD and will discuss its advantages over other conventional drug discovery approaches.
-
A novel time series link prediction method: Learning automata approach
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.
-
Renaissance in Antibiotic Discovery: Some Novel Approaches for Finding Drugs to Treat Bad Bugs.
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.
-
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.
-
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.
-
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
-
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.
-
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.
-
The use of web ontology languages and other semantic web tools in drug discovery.
Chen, Huajun; Xie, Guotong
2010-05-01
To optimize drug development processes, pharmaceutical companies require principled approaches to integrate disparate data on a unified infrastructure, such as the web. The semantic web, developed on the web technology, provides a common, open framework capable of harmonizing diversified resources to enable networked and collaborative drug discovery. We survey the state of art of utilizing web ontologies and other semantic web technologies to interlink both data and people to support integrated drug discovery across domains and multiple disciplines. Particularly, the survey covers three major application categories including: i) semantic integration and open data linking; ii) semantic web service and scientific collaboration and iii) semantic data mining and integrative network analysis. The reader will gain: i) basic knowledge of the semantic web technologies; ii) an overview of the web ontology landscape for drug discovery and iii) a basic understanding of the values and benefits of utilizing the web ontologies in drug discovery. i) The semantic web enables a network effect for linking open data for integrated drug discovery; ii) The semantic web service technology can support instant ad hoc collaboration to improve pipeline productivity and iii) The semantic web encourages publishing data in a semantic way such as resource description framework attributes and thus helps move away from a reliance on pure textual content analysis toward more efficient semantic data mining.
-
G-protein-coupled receptors: new approaches to maximise the impact of GPCRS in drug discovery.
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.
-
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.
-
A systematic approach to novel virus discovery in emerging infectious disease outbreaks.
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.
-
Executing SPARQL Queries over the Web of Linked Data
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.
-
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.
-
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.
-
Discovery of Boolean metabolic networks: integer linear programming based approach.
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 ".
-
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.
-
Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.
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.
-
Fragment-based approaches to anti-HIV drug discovery: state of the art and future opportunities.
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.
-
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
-
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…
-
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 ...
-
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.
-
The Universe Discovery Guides: A Collaborative Approach to Educating with NASA Science
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
-
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.
-
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.
-
Discovery in a World of Mashups
King, T. A.; Ritschel, B.; Hourcle, J. A.; Moon, I. S.
2014-12-01
When the first digital information was stored electronically, discovery of what existed was through file names and the organization of the file system. With the advent of networks, digital information was shared on a wider scale, but discovery remained based on file and folder names. With a growing number of information sources, named based discovery quickly became ineffective. The keyword based search engine was one of the first types of a mashup in the world of Web 1.0. Embedded links from one document to another with prescribed relationships between files and the world of Web 2.0 was formed. Search engines like Google used the links to improve search results and a worldwide mashup was formed. While a vast improvement, the need for semantic (meaning rich) discovery was clear, especially for the discovery of scientific data. In response, every science discipline defined schemas to describe their type of data. Some core schemas where shared, but most schemas are custom tailored even though they share many common concepts. As with the networking of information sources, science increasingly relies on data from multiple disciplines. So there is a need to bring together multiple sources of semantically rich information. We explore how harvesting, conceptual mapping, facet based search engines, search term promotion, and style sheets can be combined to create the next generation of mashups in the emerging world of Web 3.0. We use NASA's Planetary Data System and NASA's Heliophysics Data Environment to illustrate how to create a multi-discipline mash-up.
-
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
-
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
-
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.
-
Discovery of inhibitors of bacterial histidine kinases
Velikova, N.R.
2014-01-01
Discovery of Inhibitors of Bacterial Histidine Kinases Summary
The thesis is on novel antibacterial drug discovery (http://youtu.be/NRMWOGgeysM). Using structure-based and fragment-based drug discovery approach, we have identified small-molecule histidine-kinase
-
A Fine-Grained API Link Prediction Approach Supporting CMDA Mashup Recommendation
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
-
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...
-
A hybrid linked data approach to support asset management
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
-
Beyond information retrieval: information discovery and multimedia information retrieval
Roberto Raieli
2017-01-01
The paper compares the current methodologies for search and discovery of information and information resources: terminological search and term-based language, own of information retrieval (IR); semantic search and information discovery, being developed mainly through the language of linked data; semiotic search and content-based language, experienced by multimedia information retrieval (MIR).MIR semiotic methodology is, then, detailed.
-
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
-
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
-
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)
-
Representation Discovery using Harmonic Analysis
Mahadevan, Sridhar
2008-01-01
Representations are at the heart of artificial intelligence (AI). This book is devoted to the problem of representation discovery: how can an intelligent system construct representations from its experience? Representation discovery re-parameterizes the state space - prior to the application of information retrieval, machine learning, or optimization techniques - facilitating later inference processes by constructing new task-specific bases adapted to the state space geometry. This book presents a general approach to representation discovery using the framework of harmonic analysis, in particu
-
Link Performance Analysis and monitoring - A unified approach to divergent requirements
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.
-
Lorenz, Daniel A; Song, James M; Garner, Amanda L
2015-01-21
MicroRNAs (miRNA) play critical roles in human development and disease. As such, the targeting of miRNAs is considered attractive as a novel therapeutic strategy. A major bottleneck toward this goal, however, has been the identification of small molecule probes that are specific for select RNAs and methods that will facilitate such discovery efforts. Using pre-microRNAs as proof-of-concept, herein we report a conceptually new and innovative approach for assaying RNA-small molecule interactions. Through this platform assay technology, which we term catalytic enzyme-linked click chemistry assay or cat-ELCCA, we have designed a method that can be implemented in high throughput, is virtually free of false readouts, and is general for all nucleic acids. Through cat-ELCCA, we envision the discovery of selective small molecule ligands for disease-relevant miRNAs to promote the field of RNA-targeted drug discovery and further our understanding of the role of miRNAs in cellular biology.
-
Acetone-Linked Peptides: A Convergent Approach for Peptide Macrocyclization and Labeling.
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.
-
New approaches to e-reserve linking, sharing and streaming
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
-
Nonlinear degradation of a visible-light communication link: A Volterra-series approach
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.
-
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.…
-
Synthetic biology of antimicrobial discovery.
Zakeri, Bijan; Lu, Timothy K
2013-07-19
Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug-resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery.
-
Computational discovery of picomolar Q(o) site inhibitors of cytochrome bc1 complex.
Hao, Ge-Fei; Wang, Fu; Li, Hui; Zhu, Xiao-Lei; Yang, Wen-Chao; Huang, Li-Shar; Wu, Jia-Wei; Berry, Edward A; Yang, Guang-Fu
2012-07-11
A critical challenge to the fragment-based drug discovery (FBDD) is its low-throughput nature due to the necessity of biophysical method-based fragment screening. Herein, a method of pharmacophore-linked fragment virtual screening (PFVS) was successfully developed. Its application yielded the first picomolar-range Q(o) site inhibitors of the cytochrome bc(1) complex, an important membrane protein for drug and fungicide discovery. Compared with the original hit compound 4 (K(i) = 881.80 nM, porcine bc(1)), the most potent compound 4f displayed 20 507-fold improved binding affinity (K(i) = 43.00 pM). Compound 4f was proved to be a noncompetitive inhibitor with respect to the substrate cytochrome c, but a competitive inhibitor with respect to the substrate ubiquinol. Additionally, we determined the crystal structure of compound 4e (K(i) = 83.00 pM) bound to the chicken bc(1) at 2.70 Å resolution, providing a molecular basis for understanding its ultrapotency. To our knowledge, this study is the first application of the FBDD method in the discovery of picomolar inhibitors of a membrane protein. This work demonstrates that the novel PFVS approach is a high-throughput drug discovery method, independent of biophysical screening techniques.
-
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.
-
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...
-
Synthetic biology of antimicrobial discovery
Zakeri, Bijan; Lu, Timothy K.
2012-01-01
Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251
-
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.
-
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.
-
Pharmacological screening technologies for venom peptide discovery.
Prashanth, Jutty Rajan; Hasaballah, Nojod; Vetter, Irina
2017-12-01
Venomous animals occupy one of the most successful evolutionary niches and occur on nearly every continent. They deliver venoms via biting and stinging apparatuses with the aim to rapidly incapacitate prey and deter predators. This has led to the evolution of venom components that act at a number of biological targets - including ion channels, G-protein coupled receptors, transporters and enzymes - with exquisite selectivity and potency, making venom-derived components attractive pharmacological tool compounds and drug leads. In recent years, plate-based pharmacological screening approaches have been introduced to accelerate venom-derived drug discovery. A range of assays are amenable to this purpose, including high-throughput electrophysiology, fluorescence-based functional and binding assays. However, despite these technological advances, the traditional activity-guided fractionation approach is time-consuming and resource-intensive. The combination of screening techniques suitable for miniaturization with sequence-based discovery approaches - supported by advanced proteomics, mass spectrometry, chromatography as well as synthesis and expression techniques - promises to further improve venom peptide discovery. Here, we discuss practical aspects of establishing a pipeline for venom peptide drug discovery with a particular emphasis on pharmacology and pharmacological screening approaches. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.
-
A Weakest-Link Approach for Fatigue Limit of 30CrNiMo8 Steels (Preprint)
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
-
Thought for food (safety) in the EU: a discourse-analytical approach
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
-
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.
-
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.
-
Discovery – The Link to H.Pylori Bacteria
NCI supported research to solidify the link between H. pylori infections and stomach cancer. As a result, new cancer treatment and prevention strategies are being developed, encouraging scientists to carefully examine other cancers for viral and bacterial connections.
-
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
-
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 ...
-
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...
-
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...
-
Contextual Approach with Guided Discovery Learning and Brain Based Learning in Geometry Learning
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.
-
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.
-
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…
-
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:
-
Accounting for discovery bias in genomic prediction
Our objective was to evaluate an approach to mitigating discovery bias in genomic prediction. Accuracy may be improved by placing greater emphasis on regions of the genome expected to be more influential on a trait. Methods emphasizing regions result in a phenomenon known as “discovery bias” if info...
-
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.
-
Optogenetic Approaches to Drug Discovery in Neuroscience and Beyond.
Zhang, Hongkang; Cohen, Adam E
2017-07-01
Recent advances in optogenetics have opened new routes to drug discovery, particularly in neuroscience. Physiological cellular assays probe functional phenotypes that connect genomic data to patient health. Optogenetic tools, in particular tools for all-optical electrophysiology, now provide a means to probe cellular disease models with unprecedented throughput and information content. These techniques promise to identify functional phenotypes associated with disease states and to identify compounds that improve cellular function regardless of whether the compound acts directly on a target or through a bypass mechanism. This review discusses opportunities and unresolved challenges in applying optogenetic techniques throughout the discovery pipeline - from target identification and validation, to target-based and phenotypic screens, to clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.
-
Novel approaches to develop community-built biological network models for potential drug discovery.
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.
-
Bioinformatics in translational drug discovery.
Wooller, Sarah K; Benstead-Hume, Graeme; Chen, Xiangrong; Ali, Yusuf; Pearl, Frances M G
2017-08-31
Bioinformatics approaches are becoming ever more essential in translational drug discovery both in academia and within the pharmaceutical industry. Computational exploitation of the increasing volumes of data generated during all phases of drug discovery is enabling key challenges of the process to be addressed. Here, we highlight some of the areas in which bioinformatics resources and methods are being developed to support the drug discovery pipeline. These include the creation of large data warehouses, bioinformatics algorithms to analyse 'big data' that identify novel drug targets and/or biomarkers, programs to assess the tractability of targets, and prediction of repositioning opportunities that use licensed drugs to treat additional indications. © 2017 The Author(s).
-
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
-
A Bioinorganic Approach to Fragment-Based Drug Discovery Targeting Metalloenzymes.
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
-
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.
-
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.
-
Empowering pharmacoinformatics by linked life science data.
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.
-
Deep-Sea Microbes: Linking Biogeochemical Rates to -Omics Approaches
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.
-
Discovery of Intermetallic Compounds from Traditional to Machine-Learning Approaches.
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
-
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.
-
Predictors of timing of pregnancy discovery.
McCarthy, Molly; Upadhyay, Ushma; Biggs, M Antonia; Anthony, Renaisa; Holl, Jennifer; Roberts, Sarah Cm
2018-04-01
Earlier pregnancy discovery is important in the context of prenatal and abortion care. We evaluated characteristics associated with later pregnancy discovery among women seeking abortion care. Data come from a survey of women seeking abortion care at four family planning facilities in Utah. The participants completed a survey during the state-mandated abortion information visit they are required to complete prior to having an abortion. The outcome in this study was pregnancy discovery before versus after 6 weeks since respondents' last menstrual period (LMP). We used logistic regression to estimate the relationship between sociodemographic and health-related independent variables of interest and pregnancy discovery before versus after 6 weeks. Among the 458 women in the sample, 28% discovered their pregnancy later than 6 weeks since LMP. Most (n=366, 80%) knew the exact date of their LMP and a significant minority estimated it (n=92, 20%). Those who estimated the date of their LMP had higher odds of later pregnancy discovery than those who knew the exact date (adjusted odds ratio (aOR)=1.81[1.07-3.07]). Those who used illicit drugs weekly, daily, or almost daily had higher odds of later pregnancy discovery (aOR=6.33[2.44, 16.40]). Women who did not track their menstrual periods and those who frequently used drugs had higher odds of discovering their pregnancies later. Women who estimated the date of their LMP and who frequently used drugs may benefit from strategies to help them recognize their pregnancies earlier and link them to care when they discover their pregnancies later. Copyright © 2017 Elsevier Inc. All rights reserved.
-
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
-
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.
-
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
-
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.
-
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...
-
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.
-
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.
-
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.
-
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.
-
Handling Neighbor Discovery and Rendezvous Consistency with Weighted Quorum-Based Approach.
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.
-
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.
-
Zhang, Lu; Tan, Jianjun; Han, Dan; Zhu, Hao
2017-11-01
Machine intelligence, which is normally presented as artificial intelligence, refers to the intelligence exhibited by computers. In the history of rational drug discovery, various machine intelligence approaches have been applied to guide traditional experiments, which are expensive and time-consuming. Over the past several decades, machine-learning tools, such as quantitative structure-activity relationship (QSAR) modeling, were developed that can identify potential biological active molecules from millions of candidate compounds quickly and cheaply. However, when drug discovery moved into the era of 'big' data, machine learning approaches evolved into deep learning approaches, which are a more powerful and efficient way to deal with the massive amounts of data generated from modern drug discovery approaches. Here, we summarize the history of machine learning and provide insight into recently developed deep learning approaches and their applications in rational drug discovery. We suggest that this evolution of machine intelligence now provides a guide for early-stage drug design and discovery in the current big data era. Copyright © 2017 Elsevier Ltd. All rights reserved.
-
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.
-
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...
-
Directory of Open Access Journals (Sweden)
Nur Choiro Siregar
2015-11-01
Full Text Available Penelitian ini bertujuan menyelidiki pengaruh pembelajaran segiempat dan segitiga dengan pendekatan discovery yang menekankan aspek analogi terhadap prestasi belajar, kemampuan penalaran, dan kecerdasan emosional spiritual siswa SMP Negeri 9 Yogyakarta. Penelitian ini merupakan penelitian eksperimen semu.Instrumen yang digunakan adalah tes prestasi belajar, tes kemampuan penalaran, dan angket kecerdasan emosional spiritual. Data dianalisis menggunakan uji Multivariate Analysis of Variance (Manova dan Analysis of Variance (Anova. Hasil penelitian menunjukkan ada pengaruh pembelajaran segiempat dan segitiga dengan pendekatan discovery yang menekankan aspek analogi terhadap prestasi belajar, dan kemampuan penalaran siswa. Berdasarkan analisis, pembelajaran segiempat dan segitiga dengan pendekatan discovery yang menekankan aspek analogi lebih unggul daripada pembelajaran biasa dalam hal prestasi belajar dan kemampuan penalaran. Sebaliknya, dalam hal kecerdasan emosional spiritual siswa, pendekatan discovery yang menekankan aspek analogi tidak memberi pengaruh dan tidak lebih unggul daripada pembelajaran biasa. Kata Kunci: discovery, menekankan aspek analogi, prestasi belajar, kemampuan penalaran, kecerdasan emosional spiritual THE EFFECT OF DISCOVERY APPROACH EMPHASING ON THE ANALOGY ASPECT ON ACHIEVEMENT, REASONING ABILITY, EMOTIONAL SPIRITUAL INTELLIGENCE Abstract This study aims to investigate the effect of quadrilateral and triangle teaching using the disco-very approach emphasing on the analogy aspect on achievement, reasoning ability, and emotional spiritual intelligenceof Grade VII students of SMPN 9 Yogyakarta. This study was a quasi-experimen-tal study. The instruments of the study were an achievement test, reasoning ability test, and emotional spiritual intelligence questionnaire. The data wereanalyzed using the Multivariate Analysis of Variance (Manova and Analysis of Variance(Anova tests. The results of the study are as follows. There
-
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....
-
Arrayed antibody library technology for therapeutic biologic discovery.
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.
-
Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity
Directory of Open Access Journals (Sweden)
Bianca Zingales
2014-09-01
Full Text Available This opinion piece presents an approach to standardisation of an important aspect of Chagas disease drug discovery and development: selecting Trypanosoma cruzi strains for in vitro screening. We discuss the rationale for strain selection representing T. cruzi diversity and provide recommendations on the preferred parasite stage for drug discovery, T. cruzi discrete typing units to include in the panel of strains and the number of strains/clones for primary screens and lead compounds. We also consider experimental approaches for in vitro drug assays. The Figure illustrates the current Chagas disease drug-discovery and development landscape.
-
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…
-
Proteomic Approaches in Biomarker Discovery: New Perspectives in Cancer Diagnostics
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
-
International Drug Discovery Science and Technology--BIT's Seventh Annual Congress.
Bodovitz, Steven
2010-01-01
BIT's Seventh Annual International Drug Discovery Science and Technology Congress, held in Shanghai, included topics covering new therapeutic and technological developments in the field of drug discovery. This conference report highlights selected presentations on open-access approaches to R&D, novel and multifactorial targets, and technologies that assist drug discovery. Investigational drugs discussed include the anticancer agents astuprotimut-r (GlaxoSmithKline plc) and AS-1411 (Antisoma plc).
-
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...
-
Instruction, Repetition, Discovery: Restoring the Historical Educational Role of Practice
Trninic, Dragan
2018-01-01
This conceptual paper considers what it would mean to take seriously Freudenthal's suggestion that mathematics should be taught like swimming. The general claim being made is that "direct instruction" and "discovery" are not opposite but complementary, linked by repetitive yet explorative practice. This claim is elaborated…
-
Venomics-Accelerated Cone Snail Venom Peptide Discovery
Himaya, S. W. A.
2018-01-01
Cone snail venoms are considered a treasure trove of bioactive peptides. Despite over 800 species of cone snails being known, each producing over 1000 venom peptides, only about 150 unique venom peptides are structurally and functionally characterized. To overcome the limitations of the traditional low-throughput bio-discovery approaches, multi-omics systems approaches have been introduced to accelerate venom peptide discovery and characterisation. This “venomic” approach is starting to unravel the full complexity of cone snail venoms and to provide new insights into their biology and evolution. The main challenge for venomics is the effective integration of transcriptomics, proteomics, and pharmacological data and the efficient analysis of big datasets. Novel database search tools and visualisation techniques are now being introduced that facilitate data exploration, with ongoing advances in related omics fields being expected to further enhance venomics studies. Despite these challenges and future opportunities, cone snail venomics has already exponentially expanded the number of novel venom peptide sequences identified from the species investigated, although most novel conotoxins remain to be pharmacologically characterised. Therefore, efficient high-throughput peptide production systems and/or banks of miniaturized discovery assays are required to overcome this bottleneck and thus enhance cone snail venom bioprospecting and accelerate the identification of novel drug leads. PMID:29522462
-
Venomics-Accelerated Cone Snail Venom Peptide Discovery
Directory of Open Access Journals (Sweden)
S. W. A. Himaya
2018-03-01
Full Text Available Cone snail venoms are considered a treasure trove of bioactive peptides. Despite over 800 species of cone snails being known, each producing over 1000 venom peptides, only about 150 unique venom peptides are structurally and functionally characterized. To overcome the limitations of the traditional low-throughput bio-discovery approaches, multi-omics systems approaches have been introduced to accelerate venom peptide discovery and characterisation. This “venomic” approach is starting to unravel the full complexity of cone snail venoms and to provide new insights into their biology and evolution. The main challenge for venomics is the effective integration of transcriptomics, proteomics, and pharmacological data and the efficient analysis of big datasets. Novel database search tools and visualisation techniques are now being introduced that facilitate data exploration, with ongoing advances in related omics fields being expected to further enhance venomics studies. Despite these challenges and future opportunities, cone snail venomics has already exponentially expanded the number of novel venom peptide sequences identified from the species investigated, although most novel conotoxins remain to be pharmacologically characterised. Therefore, efficient high-throughput peptide production systems and/or banks of miniaturized discovery assays are required to overcome this bottleneck and thus enhance cone snail venom bioprospecting and accelerate the identification of novel drug leads.
-
NetiNeti: discovery of scientific names from text using machine learning methods
Directory of Open Access Journals (Sweden)
Akella Lakshmi
2012-08-01
Full Text Available Abstract Background A scientific name for an organism can be associated with almost all biological data. Name identification is an important step in many text mining tasks aiming to extract useful information from biological, biomedical and biodiversity text sources. A scientific name acts as an important metadata element to link biological information. Results We present NetiNeti (Name Extraction from Textual Information-Name Extraction for Taxonomic Indexing, a machine learning based approach for recognition of scientific names including the discovery of new species names from text that will also handle misspellings, OCR errors and other variations in names. The system generates candidate names using rules for scientific names and applies probabilistic machine learning methods to classify names based on structural features of candidate names and features derived from their contexts. NetiNeti can also disambiguate scientific names from other names using the contextual information. We evaluated NetiNeti on legacy biodiversity texts and biomedical literature (MEDLINE. NetiNeti performs better (precision = 98.9% and recall = 70.5% compared to a popular dictionary based approach (precision = 97.5% and recall = 54.3% on a 600-page biodiversity book that was manually marked by an annotator. On a small set of PubMed Central’s full text articles annotated with scientific names, the precision and recall values are 98.5% and 96.2% respectively. NetiNeti found more than 190,000 unique binomial and trinomial names in more than 1,880,000 PubMed records when used on the full MEDLINE database. NetiNeti also successfully identifies almost all of the new species names mentioned within web pages. Conclusions We present NetiNeti, a machine learning based approach for identification and discovery of scientific names. The system implementing the approach can be accessed at http://namefinding.ubio.org.
-
Scaling the walls of discovery: using semantic metadata for integrative problem solving.
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.
-
Directory of Open Access Journals (Sweden)
Ira Vahlia
2017-06-01
Full Text Available Appropriate learning models contribute to student learning interest in math. The purpose of this study is to describe the difference in effectiveness between scientific approach based on group investigation and discovery in terms of student's interest in learning. The research that is conducted is quasi experimental research and the design used is 2 x factorial description. In experimental class I that apply scientific approach model based on study group investigation obtained the average value of learning outcome of 66.60 while in the experimental class II applying the approach Science-based discovery learning obtained the average value of posttest of 76.28. Based on the marginal rate, the scientific approach to discovery-based learning on moderate interest in learning outcomes is higher than the learning outcomes at high and low interest. In the scientific approach based on group study investigation and discovery learning there are differences in average learning outcomes between high, medium and low interest. Scientific approach based on group investigation learning on higher interest in learning outcomes is higher than moderate and low interest.
-
A semantically rich and standardised approach enhancing discovery of sensor data and metadata
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
-
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…
-
When fragments link : a bibliometric perspective on the development of fragment-based drug discovery
Romasanta, A.K.S.; van der Sijde, P.C.; Hellsten, I.; Hubbard, Roderick E.; Keseru, Gyorgy M.; van Muijlwijk-Koezen, Jacqueline E.; de Esch, I.J.P.
2018-01-01
Fragment-based drug discovery (FBDD) is a highly interdisciplinary field, rich in ideas integrated from pharmaceutical sciences, chemistry, biology, and physics, among others. To enrich our understanding of the development of the field, we used bibliometric techniques to analyze 3642 publications in
-
Cell and small animal models for phenotypic drug discovery
Directory of Open Access Journals (Sweden)
Szabo M
2017-06-01
Full Text Available Mihaly Szabo,1 Sara Svensson Akusjärvi,1 Ankur Saxena,1 Jianping Liu,2 Gayathri Chandrasekar,1 Satish S Kitambi1 1Department of Microbiology Tumor, and Cell Biology, 2Department of Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden Abstract: The phenotype-based drug discovery (PDD approach is re-emerging as an alternative platform for drug discovery. This review provides an overview of the various model systems and technical advances in imaging and image analyses that strengthen the PDD platform. In PDD screens, compounds of therapeutic value are identified based on the phenotypic perturbations produced irrespective of target(s or mechanism of action. In this article, examples of phenotypic changes that can be detected and quantified with relative ease in a cell-based setup are discussed. In addition, a higher order of PDD screening setup using small animal models is also explored. As PDD screens integrate physiology and multiple signaling mechanisms during the screening process, the identified hits have higher biomedical applicability. Taken together, this review highlights the advantages gained by adopting a PDD approach in drug discovery. Such a PDD platform can complement target-based systems that are currently in practice to accelerate drug discovery. Keywords: phenotype, screening, PDD, discovery, zebrafish, drug
-
Application of lean manufacturing concepts to drug discovery: rapid analogue library synthesis.
Weller, Harold N; Nirschl, David S; Petrillo, Edward W; Poss, Michael A; Andres, Charles J; Cavallaro, Cullen L; Echols, Martin M; Grant-Young, Katherine A; Houston, John G; Miller, Arthur V; Swann, R Thomas
2006-01-01
The application of parallel synthesis to lead optimization programs in drug discovery has been an ongoing challenge since the first reports of library synthesis. A number of approaches to the application of parallel array synthesis to lead optimization have been attempted over the years, ranging from widespread deployment by (and support of) individual medicinal chemists to centralization as a service by an expert core team. This manuscript describes our experience with the latter approach, which was undertaken as part of a larger initiative to optimize drug discovery. In particular, we highlight how concepts taken from the manufacturing sector can be applied to drug discovery and parallel synthesis to improve the timeliness and thus the impact of arrays on drug discovery.
-
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.
-
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.
-
Rationale for a natural products approach to herbicide discovery.
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.
-
Developing integrated crop knowledge networks to advance candidate gene discovery.
Hassani-Pak, Keywan; Castellote, Martin; Esch, Maria; Hindle, Matthew; Lysenko, Artem; Taubert, Jan; Rawlings, Christopher
2016-12-01
The chances of raising crop productivity to enhance global food security would be greatly improved if we had a complete understanding of all the biological mechanisms that underpinned traits such as crop yield, disease resistance or nutrient and water use efficiency. With more crop genomes emerging all the time, we are nearer having the basic information, at the gene-level, to begin assembling crop gene catalogues and using data from other plant species to understand how the genes function and how their interactions govern crop development and physiology. Unfortunately, the task of creating such a complete knowledge base of gene functions, interaction networks and trait biology is technically challenging because the relevant data are dispersed in myriad databases in a variety of data formats with variable quality and coverage. In this paper we present a general approach for building genome-scale knowledge networks that provide a unified representation of heterogeneous but interconnected datasets to enable effective knowledge mining and gene discovery. We describe the datasets and outline the methods, workflows and tools that we have developed for creating and visualising these networks for the major crop species, wheat and barley. We present the global characteristics of such knowledge networks and with an example linking a seed size phenotype to a barley WRKY transcription factor orthologous to TTG2 from Arabidopsis, we illustrate the value of integrated data in biological knowledge discovery. The software we have developed (www.ondex.org) and the knowledge resources (http://knetminer.rothamsted.ac.uk) we have created are all open-source and provide a first step towards systematic and evidence-based gene discovery in order to facilitate crop improvement.
-
Four disruptive strategies for removing drug discovery bottlenecks.
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.
-
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.
-
Orphan diseases: state of the drug discovery art.
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.
-
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.
-
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...
-
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...
-
The Discovery of Insulin: A Case Study of Scientific Methodology
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…
-
An Even Better Approach : Improving the B.A.T.M.A.N. Protocol Through Formal Modelling and Analysis
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
-
Cross-Layer Service Discovery Mechanism for OLSRv2 Mobile Ad Hoc Networks
Directory of Open Access Journals (Sweden)
M. Isabel Vara
2015-07-01
Full Text Available Service discovery plays an important role in mobile ad hoc networks (MANETs. The lack of central infrastructure, limited resources and high mobility make service discovery a challenging issue for this kind of network. This article proposes a new service discovery mechanism for discovering and advertising services integrated into the Optimized Link State Routing Protocol Version 2 (OLSRv2. In previous studies, we demonstrated the validity of a similar service discovery mechanism integrated into the previous version of OLSR (OLSRv1. In order to advertise services, we have added a new type-length-value structure (TLV to the OLSRv2 protocol, called service discovery message (SDM, according to the Generalized MANET Packet/Message Format defined in Request For Comments (RFC 5444. Each node in the ad hoc network only advertises its own services. The advertisement frequency is a user-configurable parameter, so that it can be modified depending on the user requirements. Each node maintains two service tables, one to store information about its own services and another one to store information about the services it discovers in the network. We present simulation results, that compare our service discovery integrated into OLSRv2 with the one defined for OLSRv1 and with the integration of service discovery in Ad hoc On-demand Distance Vector (AODV protocol, in terms of service discovery ratio, service latency and network overhead.
-
Cross-Layer Service Discovery Mechanism for OLSRv2 Mobile Ad Hoc Networks.
Vara, M Isabel; Campo, Celeste
2015-07-20
Service discovery plays an important role in mobile ad hoc networks (MANETs). The lack of central infrastructure, limited resources and high mobility make service discovery a challenging issue for this kind of network. This article proposes a new service discovery mechanism for discovering and advertising services integrated into the Optimized Link State Routing Protocol Version 2 (OLSRv2). In previous studies, we demonstrated the validity of a similar service discovery mechanism integrated into the previous version of OLSR (OLSRv1). In order to advertise services, we have added a new type-length-value structure (TLV) to the OLSRv2 protocol, called service discovery message (SDM), according to the Generalized MANET Packet/Message Format defined in Request For Comments (RFC) 5444. Each node in the ad hoc network only advertises its own services. The advertisement frequency is a user-configurable parameter, so that it can be modified depending on the user requirements. Each node maintains two service tables, one to store information about its own services and another one to store information about the services it discovers in the network. We present simulation results, that compare our service discovery integrated into OLSRv2 with the one defined for OLSRv1 and with the integration of service discovery in Ad hoc On-demand Distance Vector (AODV) protocol, in terms of service discovery ratio, service latency and network overhead.
-
Discovery of the leinamycin family of natural products by mining actinobacterial genomes.
Pan, Guohui; Xu, Zhengren; Guo, Zhikai; Hindra; Ma, Ming; Yang, Dong; Zhou, Hao; Gansemans, Yannick; Zhu, Xiangcheng; Huang, Yong; Zhao, Li-Xing; Jiang, Yi; Cheng, Jinhua; Van Nieuwerburgh, Filip; Suh, Joo-Won; Duan, Yanwen; Shen, Ben
2017-12-26
Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm -type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.
-
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...
-
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....
-
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.
-
Multiscale approach to link red blood cell dynamics, shear viscosity, and ATP release.
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.
-
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
-
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
-
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.
-
Linking biomedical engineering ethics case study approach and policy.
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.
-
Computer-Aided Drug Discovery in Plant Pathology.
Shanmugam, Gnanendra; Jeon, Junhyun
2017-12-01
Control of plant diseases is largely dependent on use of agrochemicals. However, there are widening gaps between our knowledge on plant diseases gained from genetic/mechanistic studies and rapid translation of the knowledge into target-oriented development of effective agrochemicals. Here we propose that the time is ripe for computer-aided drug discovery/design (CADD) in molecular plant pathology. CADD has played a pivotal role in development of medically important molecules over the last three decades. Now, explosive increase in information on genome sequences and three dimensional structures of biological molecules, in combination with advances in computational and informational technologies, opens up exciting possibilities for application of CADD in discovery and development of agrochemicals. In this review, we outline two categories of the drug discovery strategies: structure- and ligand-based CADD, and relevant computational approaches that are being employed in modern drug discovery. In order to help readers to dive into CADD, we explain concepts of homology modelling, molecular docking, virtual screening, and de novo ligand design in structure-based CADD, and pharmacophore modelling, ligand-based virtual screening, quantitative structure activity relationship modelling and de novo ligand design for ligand-based CADD. We also provide the important resources available to carry out CADD. Finally, we present a case study showing how CADD approach can be implemented in reality for identification of potent chemical compounds against the important plant pathogens, Pseudomonas syringae and Colletotrichum gloeosporioides .
-
Automatic discovery of cross-family sequence features associated with protein function
Directory of Open Access Journals (Sweden)
Krings Andrea
2006-01-01
knowledge discovery in annotated sequence data. The technique is able to identify functionally important sequence features and does not require expert knowledge. By viewing protein function from a sequence perspective, the approach is also suitable for discovering unexpected links between biological processes, such as the recently discovered role of ubiquitination in transcription.
-
Literature-related discovery techniques applied to ocular disease : a vitreous restoration example
Kostoff, Ronald N.; Los, Leonoor I.
2013-01-01
Purpose of reviewLiterature-related discovery and innovation (LRDI) is a text mining approach for bridging unconnected disciplines to hypothesize radical discovery. Application to medical problems involves identifying key disease symptoms, and identifying causes and treatments for those symptoms
-
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.
-
Directory of Open Access Journals (Sweden)
Rahmi Hidayati
2017-05-01
The purpose of this study was to describe the effectiveness of setting Think Pair Share (TPS in the approach to discovery learning and problem-based learning in terms of student achievement, mathematical communication skills, and interpersonal skills of the student. This study was a quasi-experimental study using the pretest-posttest nonequivalent group design. The research population comprised all Year VIII students of SMP Negeri 1 Yogyakarta. The research sample was randomly selected from eight classes, two classes were elected. The instrument used in this study is the learning achievement test, a test of mathematical communication skills, and interpersonal skills student questionnaires. To test the effectiveness of setting Think Pair Share (TPS in the approach to discovery learning and problem-based learning, the one sample t-test was carried out. Then, to investigate the difference in effectiveness between the setting Think Pair Share (TPS in the approach to discovery learning and problem-based learning, the Multivariate Analysis of Variance (MANOVA was carried out. The research findings indicate that the setting TPS discovery approach to learning and problem-based approach to learning (PBL is effective in terms of learning achievement, mathematical communication skills, and interpersonal skills of the students. No difference in effectiveness between setting TPS discovery approach to learning and problem-based learning (PBL in terms of learning achievement, mathematical communication skills, and interpersonal skills of the students. Keywords: TPS setting in discovery learning approach, in problem-based learning, academic achievement, mathematical communication skills, and interpersonal skills of the student
-
Rule Induction-Based Knowledge Discovery for Energy Efficiency
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...
-
Linked Metadata - lightweight semantics for data integration (Invited)
Hendler, J. A.
2013-12-01
fly integration may prefer to do more traditional data queries and then convert and link the 'views' returned at retrieval time, providing another means of using the linked data infrastructure without having to convert whole datasets to triples to provide linking. Web companies have been taking advantage of 'lightweight' semantic metadata for search quality and optimization (cf. schema.org), linking networks within and without web sites (cf. Facebook's Open Graph Protocol), and in doing various kinds of advertisement and user modeling across datasets. Scientific metadata, on the other hand, has traditionally been geared at being largescale and highly descriptive, and scientific ontologies have been aimed at high expressivity, essentially providing complex reasoning services rather than the less expressive vocabularies needed for data discovery and simple mappings that can allow humans (or more complex systems) when full scale integration is needed. Although this work is just the beginning for providing integration, as the community creates more and more datasets, discovery of these data resources on the Web becomes a crucial starting place. Simple descriptors, that can be combined with textual fields and/or common community vocabularies, can be a great starting place on bringing scientific data into the Web of Data that is growing in other communities. References: [1] Pouchard, Line C., et al. "A Linked Science investigation: enhancing climate change data discovery with semantic technologies." Earth science informatics 6.3 (2013): 175-185.
-
Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders.
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.
-
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.
-
Perspectives on bioanalytical mass spectrometry and automation in drug discovery.
Janiszewski, John S; Liston, Theodore E; Cole, Mark J
2008-11-01
The use of high speed synthesis technologies has resulted in a steady increase in the number of new chemical entities active in the drug discovery research stream. Large organizations can have thousands of chemical entities in various stages of testing and evaluation across numerous projects on a weekly basis. Qualitative and quantitative measurements made using LC/MS are integrated throughout this process from early stage lead generation through candidate nomination. Nearly all analytical processes and procedures in modern research organizations are automated to some degree. This includes both hardware and software automation. In this review we discuss bioanalytical mass spectrometry and automation as components of the analytical chemistry infrastructure in pharma. Analytical chemists are presented as members of distinct groups with similar skillsets that build automated systems, manage test compounds, assays and reagents, and deliver data to project teams. The ADME-screening process in drug discovery is used as a model to highlight the relationships between analytical tasks in drug discovery. Emerging software and process automation tools are described that can potentially address gaps and link analytical chemistry related tasks. The role of analytical chemists and groups in modern 'industrialized' drug discovery is also discussed.
-
Gene Linked to Excess Male Hormones in Female Infertility Disorder
... April 15, 2014 Gene linked to excess male hormones in female infertility disorder Discovery by NIH-supported ... may lead to the overproduction of androgens — male hormones similar to testosterone — occurring in women with polycystic ...
-
Tick-borne pathogen – Reversed and conventional discovery of disease
Directory of Open Access Journals (Sweden)
Ellen eTijsse Klasen
2014-07-01
Full Text Available Molecular methods have increased the number of known microorganisms associated with ticks significantly. Some of these newly identified microorganisms are readily linked to human disease while others are yet unknown to cause human disease. The face of tick-borne disease discovery has changed with more diseases now being discovered in a ‘reversed way’, detecting disease cases only years after the tick-borne microorganism was first discovered. Compared to the conventional discovery of infectious diseases, this order of discoveries presents researchers with new challenges. Especially estimating public health risks of such agents is challenging, as case definitions and diagnostic procedures may initially be missing. We discuss the advantages and shortcomings of molecular methods, serology, epidemiological studies that might be used to study some fundamental questions regarding newly identified tick-borne diseases. With increased tick-exposure and improved detection methods, more tick-borne microorganisms will be added to the list of pathogens causing disease in humans in future.
-
Medicinal chemistry inspired fragment-based drug discovery.
Lanter, James; Zhang, Xuqing; Sui, Zhihua
2011-01-01
Lead generation can be a very challenging phase of the drug discovery process. The two principal methods for this stage of research are blind screening and rational design. Among the rational or semirational design approaches, fragment-based drug discovery (FBDD) has emerged as a useful tool for the generation of lead structures. It is particularly powerful as a complement to high-throughput screening approaches when the latter failed to yield viable hits for further development. Engagement of medicinal chemists early in the process can accelerate the progression of FBDD efforts by incorporating drug-friendly properties in the earliest stages of the design process. Medium-chain acyl-CoA synthetase 2b and ketohexokinase are chosen as examples to illustrate the importance of close collaboration of medicinal chemists, crystallography, and modeling. Copyright © 2011 Elsevier Inc. All rights reserved.
-
Exploring relation types for literature-based discovery.
Preiss, Judita; Stevenson, Mark; Gaizauskas, Robert
2015-09-01
Literature-based discovery (LBD) aims to identify "hidden knowledge" in the medical literature by: (1) analyzing documents to identify pairs of explicitly related concepts (terms), then (2) hypothesizing novel relations between pairs of unrelated concepts that are implicitly related via a shared concept to which both are explicitly related. Many LBD approaches use simple techniques to identify semantically weak relations between concepts, for example, document co-occurrence. These generate huge numbers of hypotheses, difficult for humans to assess. More complex techniques rely on linguistic analysis, for example, shallow parsing, to identify semantically stronger relations. Such approaches generate fewer hypotheses, but may miss hidden knowledge. The authors investigate this trade-off in detail, comparing techniques for identifying related concepts to discover which are most suitable for LBD. A generic LBD system that can utilize a range of relation types was developed. Experiments were carried out comparing a number of techniques for identifying relations. Two approaches were used for evaluation: replication of existing discoveries and the "time slicing" approach.(1) RESULTS: Previous LBD discoveries could be replicated using relations based either on document co-occurrence or linguistic analysis. Using relations based on linguistic analysis generated many fewer hypotheses, but a significantly greater proportion of them were candidates for hidden knowledge. The use of linguistic analysis-based relations improves accuracy of LBD without overly damaging coverage. LBD systems often generate huge numbers of hypotheses, which are infeasible to manually review. Improving their accuracy has the potential to make these systems significantly more usable. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.
-
Benmansour, Fatiha; Trist, Iuni; Coutard, Bruno; Decroly, Etienne; Querat, Gilles; Brancale, Andrea; Barral, Karine
2017-01-05
With the aim to help drug discovery against dengue virus (DENV), a fragment-based drug design approach was applied to identify ligands targeting a main component of DENV replication complex: the NS5 AdoMet-dependent mRNA methyltransferase (MTase) domain, playing an essential role in the RNA capping process. Herein, we describe the identification of new inhibitors developed using fragment-based, structure-guided linking and optimization techniques. Thermal-shift assay followed by a fragment-based X-ray crystallographic screening lead to the identification of three fragment hits binding DENV MTase. We considered linking two of them, which bind to proximal sites of the AdoMet binding pocket, in order to improve their potency. X-ray crystallographic structures and computational docking were used to guide the fragment linking, ultimately leading to novel series of non-nucleoside inhibitors of flavivirus MTase, respectively N-phenyl-[(phenylcarbamoyl)amino]benzene-1-sulfonamide and phenyl [(phenylcarbamoyl)amino]benzene-1-sulfonate derivatives, that show a 10-100-fold stronger inhibition of 2'-O-MTase activity compared to the initial fragments. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
-
Linked Data: what does it offer Earth Sciences?
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
-
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.
-
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.
-
Providing Fast Discovery in D2D Communication with Full Duplex Technology
DEFF Research Database (Denmark)
Gatnau, Marta; Berardinelli, Gilberto; Mahmood, Nurul Huda
2016-01-01
technology to provide D2D fast discovery. Such framework provides an algorithm to estimate the number of neighbor devices and to dynamically decide the transmission probability, for adapting to network changes and meeting the 10 milliseconds target. Finally, a signaling scheme is proposed to reduce......In Direct Device-to-Device (D2D), the device awareness procedure known as the discovery phase is required prior to the exchange of data. This work considers autonomous devices where the infrastructure is not involved in the discovery procedure. Commonly, the transmission of the discovery message...... the network interference. Results show that our framework performs better than a static approach, reducing the time it takes to complete the discovery phase. In addition, supporting full duplex allows to further reduce the discovery time compared to half duplex transmission mode....
-
Neptune's Discovery: Le Verrier, Adams, and the Assignment of Credit
Sheehan, William
2011-01-01
As one of the most significant achievements of 19th century astronomy, the discovery of Neptune has been the subject of a vast literature. A large part of this literature--beginning with the period immediately after the optical discovery in Berlin--has been the obsession with assigning credit to the two men who attempted to calculate the planet's position (and initially this played out against the international rivalry between France and England). Le Verrier and Adams occupied much different positions in the Scientific Establishments of their respective countries; had markedly different personalities; and approached the investigation using different methods. A psychiatrist and historian of astronomy tries to provide some new contexts to the familiar story of the discovery of Neptune, and argues that the personalities of these two men played crucial roles in their approaches to the problem they set themselves and the way others reacted to their stimuli. Adams had features of high-functioning autism, while Le Verrier's domineering, obsessive, orderly personality--though it allowed him to be immensely productive--eventually led to serious difficulties with his peers (and an outright revolt). Though it took extraordinary smarts to calculate the position of Neptune, the discovery required social skills that these men lacked--and thus the process to discovery was more bumbling and adventitious than it might have been. The discovery of Neptune occurred at a moment when astronomy was changing from that of heroic individuals to team collaborations involving multiple experts, and remains an object lesson in the sociological aspects of scientific endeavor.
-
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.
-
Novel approach of fragment-based lead discovery applied to renin inhibitors.
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.
-
Comment on "drug discovery: turning the titanic".
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.
-
"Discoveries in Planetary Sciences": Slide Sets Highlighting New Advances for Astronomy Educators
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
-
New perspectives on innovative drug discovery: an overview.
Pan, Si Yuan; Pan, Shan; Yu, Zhi-Ling; Ma, Dik-Lung; Chen, Si-Bao; Fong, Wang-Fun; Han, Yi-Fan; Ko, Kam-Ming
2010-01-01
Despite advances in technology, drug discovery is still a lengthy, expensive, difficult, and inefficient process, with a low rate of success. Today, advances in biomedical science have brought about great strides in therapeutic interventions for a wide spectrum of diseases. The advent of biochemical techniques and cutting-edge bio/chemical technologies has made available a plethora of practical approaches to drug screening and design. In 2010, the total sales of the global pharmaceutical market will reach 600 billion US dollars and expand to over 975 billion dollars by 2013. The aim of this review is to summarize available information on contemporary approaches and strategies in the discovery of novel therapeutic agents, especially from the complementary and alternative medicines, including natural products and traditional remedies such as Chinese herbal medicine.
-
The limits of de novo DNA motif discovery.
Directory of Open Access Journals (Sweden)
David Simcha
Full Text Available A major challenge in molecular biology is reverse-engineering the cis-regulatory logic that plays a major role in the control of gene expression. This program includes searching through DNA sequences to identify "motifs" that serve as the binding sites for transcription factors or, more generally, are predictive of gene expression across cellular conditions. Several approaches have been proposed for de novo motif discovery-searching sequences without prior knowledge of binding sites or nucleotide patterns. However, unbiased validation is not straightforward. We consider two approaches to unbiased validation of discovered motifs: testing the statistical significance of a motif using a DNA "background" sequence model to represent the null hypothesis and measuring performance in predicting membership in gene clusters. We demonstrate that the background models typically used are "too null," resulting in overly optimistic assessments of significance, and argue that performance in predicting TF binding or expression patterns from DNA motifs should be assessed by held-out data, as in predictive learning. Applying this criterion to common motif discovery methods resulted in universally poor performance, although there is a marked improvement when motifs are statistically significant against real background sequences. Moreover, on synthetic data where "ground truth" is known, discriminative performance of all algorithms is far below the theoretical upper bound, with pronounced "over-fitting" in training. A key conclusion from this work is that the failure of de novo discovery approaches to accurately identify motifs is basically due to statistical intractability resulting from the fixed size of co-regulated gene clusters, and thus such failures do not necessarily provide evidence that unfound motifs are not active biologically. Consequently, the use of prior knowledge to enhance motif discovery is not just advantageous but necessary. An implementation of
-
Benson, Neil
2015-08-01
Phase II attrition remains the most important challenge for drug discovery. Tackling the problem requires improved understanding of the complexity of disease biology. Systems biology approaches to this problem can, in principle, deliver this. This article reviews the reports of the application of mechanistic systems models to drug discovery questions and discusses the added value. Although we are on the journey to the virtual human, the length, path and rate of learning from this remain an open question. Success will be dependent on the will to invest and make the most of the insight generated along the way. Copyright © 2015 Elsevier Ltd. All rights reserved.
-
Asher, Andrew D.; Duke, Lynda M.; Wilson, Suzanne
2013-01-01
In 2011, researchers at Bucknell University and Illinois Wesleyan University compared the search efficacy of Serial Solutions Summon, EBSCO Discovery Service, Google Scholar, and conventional library databases. Using a mixed-methods approach, qualitative and quantitative data were gathered on students' usage of these tools. Regardless of the…
-
Discovery of Cationic Polymers for Non-viral Gene Delivery using Combinatorial Approaches
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
-
Equation Discovery for Financial Forcasting in Context of Islamic Banking
Institute of Scientific and Technical Information of China (English)
Amer Alzaidi; Dimitar Kazakov
2010-01-01
This paper describes an equation discovery approach based on machine leamng using LAGdtAMGE as an equation discovery tool,with two sources of input,a dataset and model presented in context-free gammar.The approach is searching a large range of potential equations by a specific model.The parameters of the equation are fitted to find the best equations.The The experiments are illustratedwith commodity prices from the London Metal Exchange for the period of January-October 2009.The outputs of the experiments are a large number of equations;same of the equations display that the predicted rakes are following the market trends in perfect patterns.
-
Search strategy has influenced the discovery rate of human viruses.
Rosenberg, Ronald; Johansson, Michael A; Powers, Ann M; Miller, Barry R
2013-08-20
A widely held concern is that the pace of infectious disease emergence has been increasing. We have analyzed the rate of discovery of pathogenic viruses, the preeminent source of newly discovered causes of human disease, from 1897 through 2010. The rate was highest during 1950-1969, after which it moderated. This general picture masks two distinct trends: for arthropod-borne viruses, which comprised 39% of pathogenic viruses, the discovery rate peaked at three per year during 1960-1969, but subsequently fell nearly to zero by 1980; however, the rate of discovery of nonarboviruses remained stable at about two per year from 1950 through 2010. The period of highest arbovirus discovery coincided with a comprehensive program supported by The Rockefeller Foundation of isolating viruses from humans, animals, and arthropod vectors at field stations in Latin America, Africa, and India. The productivity of this strategy illustrates the importance of location, approach, long-term commitment, and sponsorship in the discovery of emerging pathogens.
-
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.
-
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.
-
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.
-
Bhardwaj, Anshu; Scaria, Vinod; Raghava, Gajendra Pal Singh; Lynn, Andrew Michael; Chandra, Nagasuma; Banerjee, Sulagna; Raghunandanan, Muthukurussi V; Pandey, Vikas; Taneja, Bhupesh; Yadav, Jyoti; Dash, Debasis; Bhattacharya, Jaijit; Misra, Amit; Kumar, Anil; Ramachandran, Srinivasan; Thomas, Zakir; Brahmachari, Samir K
2011-09-01
It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery. Copyright © 2011 Elsevier Ltd. All rights reserved.
-
From the nucleus discovery to DWBA; De la decouverte du noyau a la DWBA
Energy Technology Data Exchange (ETDEWEB)
Fernandez, B. [Ecole Joliot Curie, 33 - Gradignan (France)
2007-07-01
The author presents a brief review of the main events in the field of nuclear reactions that are acknowledged as milestones because of their importance due to either experimental setting or physical interpretation. It is shown that the pace of discoveries has been strongly dependent on the technical progress in detection means at the beginning of nuclear physics and now is linked to the development of simulation means. The discovery of the neutron, the development of the Geiger counter, the theory of the compound nucleus or the first direct reactions are among these milestones.
-
Nirmalanandhan, Victor Sanjit; Sittampalam, G Sitta
2009-08-01
Stem cells, irrespective of their origin, have emerged as valuable reagents or tools in human health in the past 2 decades. Initially, a research tool to study fundamental aspects of developmental biology is now the central focus of generating transgenic animals, drug discovery, and regenerative medicine to address degenerative diseases of multiple organ systems. This is because stem cells are pluripotent or multipotent cells that can recapitulate developmental paths to repair damaged tissues. However, it is becoming clear that stem cell therapy alone may not be adequate to reverse tissue and organ damage in degenerative diseases. Existing small-molecule drugs and biologicals may be needed as "molecular adjuvants" or enhancers of stem cells administered in therapy or adult stem cells in the diseased tissues. Hence, a combination of stem cell-based, high-throughput screening and 3D tissue engineering approaches is necessary to advance the next wave of tools in preclinical drug discovery. In this review, the authors have attempted to provide a basic account of various stem cells types, as well as their biology and signaling, in the context of research in regenerative medicine. An attempt is made to link stem cells as reagents, pharmacology, and tissue engineering as converging fields of research for the next decade.
-
Everett, Jeremy R
2013-03-01
The 10th Anniversary of International Drug Discovery Science and Technology (IDDST) Conference was held in Nanjing, China from 8 to 10 November 2012. The conference ran in parallel with the 2nd Annual Symposium of Drug Delivery Systems. Over 400 delegates from both conferences came together for the Opening Ceremony and Keynote Addresses but otherwise pursued separate paths in the huge facilities of the Nanjing International Expo Centre. The IDDST was arranged into 19 separate Chapters covering drug discovery biology, target validation, chemistry, rational drug design, pharmacology and toxicology, drug screening technology, 'omics' technologies, analytical, automation and enabling technologies, informatics, stem cells and regenerative medicine, bioprocessing, generics, biosimilars and biologicals and seven disease areas: cancer, CNS, respiratory and inflammation, autoimmune, emerging infectious, bone and orphan diseases. There were also two sessions of a 'Bench to Bedside to Business' Program and a Chinese Scientist programme. In each period of the IDDST conference, up to seven sessions were running in parallel. This Meeting Highlight samples just a fraction of the content of this large meeting. The talks included have as a link, the use of new approaches to drug discovery. Many other excellent talks could have been highlighted and the author has necessarily had to be selective.
-
Towards a routine application of Top-Down approaches for label-free discovery workflows.
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
-
Bradley, Anthony R; Echalier, Aude; Fairhead, Michael; Strain-Damerell, Claire; Brennan, Paul; Bullock, Alex N; Burgess-Brown, Nicola A; Carpenter, Elisabeth P; Gileadi, Opher; Marsden, Brian D; Lee, Wen Hwa; Yue, Wyatt; Bountra, Chas; von Delft, Frank
2017-11-08
The ongoing explosion in genomics data has long since outpaced the capacity of conventional biochemical methodology to verify the large number of hypotheses that emerge from the analysis of such data. In contrast, it is still a gold-standard for early phenotypic validation towards small-molecule drug discovery to use probe molecules (or tool compounds), notwithstanding the difficulty and cost of generating them. Rational structure-based approaches to ligand discovery have long promised the efficiencies needed to close this divergence; in practice, however, this promise remains largely unfulfilled, for a host of well-rehearsed reasons and despite the huge technical advances spearheaded by the structural genomics initiatives of the noughties. Therefore the current, fourth funding phase of the Structural Genomics Consortium (SGC), building on its extensive experience in structural biology of novel targets and design of protein inhibitors, seeks to redefine what it means to do structural biology for drug discovery. We developed the concept of a Target Enabling Package (TEP) that provides, through reagents, assays and data, the missing link between genetic disease linkage and the development of usefully potent compounds. There are multiple prongs to the ambition: rigorously assessing targets' genetic disease linkages through crowdsourcing to a network of collaborating experts; establishing a systematic approach to generate the protocols and data that comprise each target's TEP; developing new, X-ray-based fragment technologies for generating high quality chemical matter quickly and cheaply; and exploiting a stringently open access model to build multidisciplinary partnerships throughout academia and industry. By learning how to scale these approaches, the SGC aims to make structures finally serve genomics, as originally intended, and demonstrate how 3D structures systematically allow new modes of druggability to be discovered for whole classes of targets. © 2017 The
-
Topology Discovery Using Cisco Discovery Protocol
Rodriguez, Sergio R.
2009-01-01
In this paper we address the problem of discovering network topology in proprietary networks. Namely, we investigate topology discovery in Cisco-based networks. Cisco devices run Cisco Discovery Protocol (CDP) which holds information about these devices. We first compare properties of topologies that can be obtained from networks deploying CDP versus Spanning Tree Protocol (STP) and Management Information Base (MIB) Forwarding Database (FDB). Then we describe a method of discovering topology ...
-
Advances in fragment-based drug discovery platforms.
Orita, Masaya; Warizaya, Masaichi; Amano, Yasushi; Ohno, Kazuki; Niimi, Tatsuya
2009-11-01
Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique. Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique. Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.
-
Advancing Drug Discovery through Enhanced Free Energy Calculations.
Abel, Robert; Wang, Lingle; Harder, Edward D; Berne, B J; Friesner, Richard A
2017-07-18
A principal goal of drug discovery project is to design molecules that can tightly and selectively bind to the target protein receptor. Accurate prediction of protein-ligand binding free energies is therefore of central importance in computational chemistry and computer aided drug design. Multiple recent improvements in computing power, classical force field accuracy, enhanced sampling methods, and simulation setup have enabled accurate and reliable calculations of protein-ligands binding free energies, and position free energy calculations to play a guiding role in small molecule drug discovery. In this Account, we outline the relevant methodological advances, including the REST2 (Replica Exchange with Solute Temperting) enhanced sampling, the incorporation of REST2 sampling with convential FEP (Free Energy Perturbation) through FEP/REST, the OPLS3 force field, and the advanced simulation setup that constitute our FEP+ approach, followed by the presentation of extensive comparisons with experiment, demonstrating sufficient accuracy in potency prediction (better than 1 kcal/mol) to substantially impact lead optimization campaigns. The limitations of the current FEP+ implementation and best practices in drug discovery applications are also discussed followed by the future methodology development plans to address those limitations. We then report results from a recent drug discovery project, in which several thousand FEP+ calculations were successfully deployed to simultaneously optimize potency, selectivity, and solubility, illustrating the power of the approach to solve challenging drug design problems. The capabilities of free energy calculations to accurately predict potency and selectivity have led to the advance of ongoing drug discovery projects, in challenging situations where alternative approaches would have great difficulties. The ability to effectively carry out projects evaluating tens of thousands, or hundreds of thousands, of proposed drug candidates
-
Scientific workflows as productivity tools for drug discovery.
Shon, John; Ohkawa, Hitomi; Hammer, Juergen
2008-05-01
Large pharmaceutical companies annually invest tens to hundreds of millions of US dollars in research informatics to support their early drug discovery processes. Traditionally, most of these investments are designed to increase the efficiency of drug discovery. The introduction of do-it-yourself scientific workflow platforms has enabled research informatics organizations to shift their efforts toward scientific innovation, ultimately resulting in a possible increase in return on their investments. Unlike the handling of most scientific data and application integration approaches, researchers apply scientific workflows to in silico experimentation and exploration, leading to scientific discoveries that lie beyond automation and integration. This review highlights some key requirements for scientific workflow environments in the pharmaceutical industry that are necessary for increasing research productivity. Examples of the application of scientific workflows in research and a summary of recent platform advances are also provided.
-
PERFORMANCE EVALUATION OF AN ALTERNATIVE CONTROLLER FOR BLUETOOTH SERVICE DISCOVERY
Directory of Open Access Journals (Sweden)
M. Sughasiny
2012-06-01
Full Text Available Bluetooth is a short range radio technology to form a small wireless system. It is used in low –cost, low power ad-hoc networks and it suffers from long service discovery delay and high power consumption. Bluetooth employs the 2.4 GHz ISM band, sharing the same bandwidth with the wireless LAN implementing the IEEE 802.11 standards. Thus it causes significantly lower interference. For improving the efficiency of SDP, we present an implementation of Bluetooth 2.1 in the NS-2 simulator, discuss the IEEE 802.11b as a Bluetooth controller and propose a new alternative Bluetooth Controller based on Adaptive Frequency Hopping techniques using Amplifier Power. The resulting approach significantly reduces the service discovery time, thereby lowering power consumption and increasing the throughput. We present the benefits of our new approach and compare it with existing approach using NS-2 Simulations and we have presented the comparison graphs in support of our approach.
-
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.
-
The NCAR Research Data Archive's Hybrid Approach for Data Discovery and Access
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
-
X-Ray Astronomy Discovery Experiments, III*
Fisher, P. C.
2011-04-01
The first paper established the existence of concurrent discovery experiments by Riccardo Giacconi and myself at the start of x-ray astronomy.footnotetextR. Giacconi et al., Phys. Rev. Lett. 9, 439 (1962).^,footnotetextP. C. Fisher et al., Quasars and High Energy Astronomy including Proceedings of the 2^nd Texas Symposium on Relativistic Astrophysics 15 - 19 December 1964 (K. N. Douglas et. al., eds.) Gordon and Breach Science Publishers, New York, p. 253 (1969).^,footnotetextP. C. Fisher, BAPS 53 No. 2, 165 (2008). Paper II footnotetextP.C. Fisher, http://www.aps.org/units/fhp/index.cfm plus FHP link to April 2009 presentation H14.00006. described some acts by some individuals/institutions over four decades that may have caused the illusion that I had not made a discovery. Some additional data about this illusion, and the first possible measurement of x-ray emission from a black hole, will be presented. This paper's primary goal is for the American Physical Society to have Giacconi comment on several questions of a historical nature. [4pt] *Work supported by NASA contracts NAS5-1174 and NASw-909, the Lockheed Independent Research Program, and Ruffner Associates.
-
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.
-
Discovery Learning: Zombie, Phoenix, or Elephant?
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…
-
Astrobiology, discovery, and societal impact
Dick, Steven J
2018-01-01
The search for life in the universe, once the stuff of science fiction, is now a robust worldwide research program with a well-defined roadmap probing both scientific and societal issues. This volume examines the humanistic aspects of astrobiology, systematically discussing the approaches, critical issues, and implications of discovering life beyond Earth. What do the concepts of life and intelligence, culture and civilization, technology and communication mean in a cosmic context? What are the theological and philosophical implications if we find life - and if we do not? Steven J. Dick argues that given recent scientific findings, the discovery of life in some form beyond Earth is likely and so we need to study the possible impacts of such a discovery and formulate policies to deal with them. The remarkable and often surprising results are presented here in a form accessible to disciplines across the sciences, social sciences, and humanities.
-
Model-driven discovery of underground metabolic functions in Escherichia coli
DEFF Research Database (Denmark)
Guzmán, Gabriela I.; Utrilla, José; Nurk, Sergey
2015-01-01
-scale models, which have been widely used for predicting growth phenotypes in various environments or following a genetic perturbation; however, these predictions occasionally fail. Failed predictions of gene essentiality offer an opportunity for targeting biological discovery, suggesting the presence......E, and gltA and prpC. This study demonstrates how a targeted model-driven approach to discovery can systematically fill knowledge gaps, characterize underground metabolism, and elucidate regulatory mechanisms of adaptation in response to gene KO perturbations....
-
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...
-
Context discovery using attenuated Bloom codes: model description and validation
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
-
Directory of Open Access Journals (Sweden)
Yongyao Jiang
2016-04-01
Full Text Available Big geospatial data are archived and made available through online web discovery and access. However, finding the right data for scientific research and application development is still a challenge. This paper aims to improve the data discovery by mining the user knowledge from log files. Specifically, user web session reconstruction is focused upon in this paper as a critical step for extracting usage patterns. However, reconstructing user sessions from raw web logs has always been difficult, as a session identifier tends to be missing in most data portals. To address this problem, we propose two session identification methods, including time-clustering-based and time-referrer-based methods. We also present the workflow of session reconstruction and discuss the approach of selecting appropriate thresholds for relevant steps in the workflow. The proposed session identification methods and workflow are proven to be able to extract data access patterns for further pattern analyses of user behavior and improvement of data discovery for more relevancy data ranking, suggestion, and navigation.
-
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...
-
Bead-based screening in chemical biology and drug discovery
DEFF Research Database (Denmark)
Komnatnyy, Vitaly V.; Nielsen, Thomas Eiland; Qvortrup, Katrine
2018-01-01
libraries for early drug discovery. Among the various library forms, the one-bead-one-compound (OBOC) library, where each bead carries many copies of a single compound, holds the greatest potential for the rapid identification of novel hits against emerging drug targets. However, this potential has not yet...... been fully realized due to a number of technical obstacles. In this feature article, we review the progress that has been made towards bead-based library screening and applications to the discovery of bioactive compounds. We identify the key challenges of this approach and highlight key steps needed......High-throughput screening is an important component of the drug discovery process. The screening of libraries containing hundreds of thousands of compounds requires assays amanable to miniaturisation and automization. Combinatorial chemistry holds a unique promise to deliver structural diverse...
-
The application of mass-spectrometry-based protein biomarker discovery to theragnostics
Street, Jonathan M; Dear, James W
2010-01-01
Over the last decade rapid developments in mass spectrometry have allowed the identification of multiple proteins in complex biological samples. This proteomic approach has been applied to biomarker discovery in the context of clinical pharmacology (the combination of biomarker and drug now being termed ‘theragnostics’). In this review we provide a roadmap for early protein biomarker discovery studies, focusing on some key questions that regularly confront researchers.
-
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...
-
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.
-
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.
-
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.
-
Discovery of Five Probable Novae in M81
Hornoch, K.; Errmann, R.; Sowicka, P.; Humphries, N.; Vaduvescu, O.
2015-10-01
We report the discovery of five probable novae in M81 on a co-added 2000-s narrow-band H-alpha CCD image taken with the 2.5-m Isaac Newton Telescope (INT) + WFC at La Palma under ~1.5" seeing on 2015 Oct. 14.198 UT. The new objects are well visible on the co-added image (see the finding charts linked below), but are not present on numerous narrow-band H-alpha archival images from the INT down to limiting magnitude as faint as H-alpha = 22.3.
-
Mass spectrometry imaging enriches biomarker discovery approaches with candidate mapping.
Scott, Alison J; Jones, Jace W; Orschell, Christie M; MacVittie, Thomas J; Kane, Maureen A; Ernst, Robert K
2014-01-01
Integral to the characterization of radiation-induced tissue damage is the identification of unique biomarkers. Biomarker discovery is a challenging and complex endeavor requiring both sophisticated experimental design and accessible technology. The resources within the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Consortium, Medical Countermeasures Against Radiological Threats (MCART), allow for leveraging robust animal models with novel molecular imaging techniques. One such imaging technique, MALDI (matrix-assisted laser desorption ionization) mass spectrometry imaging (MSI), allows for the direct spatial visualization of lipids, proteins, small molecules, and drugs/drug metabolites-or biomarkers-in an unbiased manner. MALDI-MSI acquires mass spectra directly from an intact tissue slice in discrete locations across an x, y grid that are then rendered into a spatial distribution map composed of ion mass and intensity. The unique mass signals can be plotted to generate a spatial map of biomarkers that reflects pathology and molecular events. The crucial unanswered questions that can be addressed with MALDI-MSI include identification of biomarkers for radiation damage that reflect the response to radiation dose over time and the efficacy of therapeutic interventions. Techniques in MALDI-MSI also enable integration of biomarker identification among diverse animal models. Analysis of early, sublethally irradiated tissue injury samples from diverse mouse tissues (lung and ileum) shows membrane phospholipid signatures correlated with histological features of these unique tissues. This paper will discuss the application of MALDI-MSI for use in a larger biomarker discovery pipeline.
-
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
-
Bioinformatics and biomarker discovery "Omic" data analysis for personalized medicine
Azuaje, Francisco
2010-01-01
This book is designed to introduce biologists, clinicians and computational researchers to fundamental data analysis principles, techniques and tools for supporting the discovery of biomarkers and the implementation of diagnostic/prognostic systems. The focus of the book is on how fundamental statistical and data mining approaches can support biomarker discovery and evaluation, emphasising applications based on different types of "omic" data. The book also discusses design factors, requirements and techniques for disease screening, diagnostic and prognostic applications. Readers are provided w
-
The discovery of the periodic table as a case of simultaneous discovery.
Scerri, Eric
2015-03-13
The article examines the question of priority and simultaneous discovery in the context of the discovery of the periodic system. It is argued that rather than being anomalous, simultaneous discovery is the rule. Moreover, I argue that the discovery of the periodic system by at least six authors in over a period of 7 years represents one of the best examples of a multiple discovery. This notion is supported by a new view of the evolutionary development of science through a mechanism that is dubbed Sci-Gaia by analogy with Lovelock's Gaia hypothesis. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
-
BPS Pharmacology 2014 - Drug Discovery Pathways symposium Report
Marsh, Andrew
2015-01-01
Report on BPS Pharmacology 2014, BPS Industry Committe and Learned Societies Drug Discovery Pathways Group symposium: "Realizing the potential of new approaches to target identification and validation" by Dr Andrew Marsh Associate Professor Department of Chemistry University of Warwick go.warwick.ac.uk/marshgroup Twitter @marshgroup
-
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...
-
Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures
DEFF Research Database (Denmark)
Stark, Alexander; Lin, Michael F; Kheradpour, Pouya
2007-01-01
Sequencing of multiple related species followed by comparative genomics analysis constitutes a powerful approach for the systematic understanding of any genome. Here, we use the genomes of 12 Drosophila species for the de novo discovery of functional elements in the fly. Each type of functional e...... individual motif instances with high confidence. We also study how discovery power scales with the divergence and number of species compared, and we provide general guidelines for comparative studies....
-
Symbiosis-inspired approaches to antibiotic discovery.
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.
-
Mamykina, Lena; Heitkemper, Elizabeth M; Smaldone, Arlene M; Kukafka, Rita; Cole-Lewis, Heather J; Davidson, Patricia G; Mynatt, Elizabeth D; Cassells, Andrea; Tobin, Jonathan N; Hripcsak, George
2017-12-01
To outline new design directions for informatics solutions that facilitate personal discovery with self-monitoring data. We investigate this question in the context of chronic disease self-management with the focus on type 2 diabetes. We conducted an observational qualitative study of discovery with personal data among adults attending a diabetes self-management education (DSME) program that utilized a discovery-based curriculum. The study included observations of class sessions, and interviews and focus groups with the educator and attendees of the program (n = 14). The main discovery in diabetes self-management evolved around discovering patterns of association between characteristics of individuals' activities and changes in their blood glucose levels that the participants referred to as "cause and effect". This discovery empowered individuals to actively engage in self-management and provided a desired flexibility in selection of personalized self-management strategies. We show that discovery of cause and effect involves four essential phases: (1) feature selection, (2) hypothesis generation, (3) feature evaluation, and (4) goal specification. Further, we identify opportunities to support discovery at each stage with informatics and data visualization solutions by providing assistance with: (1) active manipulation of collected data (e.g., grouping, filtering and side-by-side inspection), (2) hypotheses formulation (e.g., using natural language statements or constructing visual queries), (3) inference evaluation (e.g., through aggregation and visual comparison, and statistical analysis of associations), and (4) translation of discoveries into actionable goals (e.g., tailored selection from computable knowledge sources of effective diabetes self-management behaviors). The study suggests that discovery of cause and effect in diabetes can be a powerful approach to helping individuals to improve their self-management strategies, and that self-monitoring data can
-
Discovery of pyridine-based agrochemicals by using Intermediate Derivatization Methods.
Guan, Ai-Ying; Liu, Chang-Ling; Sun, Xu-Feng; Xie, Yong; Wang, Ming-An
2016-02-01
Pyridine-based compounds have been playing a crucial role as agrochemicals or pesticides including fungicides, insecticides/acaricides and herbicides, etc. Since most of the agrochemicals listed in the Pesticide Manual were discovered through screening programs that relied on trial-and-error testing and new agrochemical discovery is not benefiting as much from the in silico new chemical compound identification/discovery techniques used in pharmaceutical research, it has become more important to find new methods to enhance the efficiency of discovering novel lead compounds in the agrochemical field to shorten the time of research phases in order to meet changing market requirements. In this review, we selected 18 representative known agrochemicals containing a pyridine moiety and extrapolate their discovery from the perspective of Intermediate Derivatization Methods in the hope that this approach will have greater appeal to researchers engaged in the discovery of agrochemicals and/or pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.
-
Translational Research 2.0: a framework for accelerating collaborative discovery.
Asakiewicz, Chris
2014-05-01
The world wide web has revolutionized the conduct of global, cross-disciplinary research. In the life sciences, interdisciplinary approaches to problem solving and collaboration are becoming increasingly important in facilitating knowledge discovery and integration. Web 2.0 technologies promise to have a profound impact - enabling reproducibility, aiding in discovery, and accelerating and transforming medical and healthcare research across the healthcare ecosystem. However, knowledge integration and discovery require a consistent foundation upon which to operate. A foundation should be capable of addressing some of the critical issues associated with how research is conducted within the ecosystem today and how it should be conducted for the future. This article will discuss a framework for enhancing collaborative knowledge discovery across the medical and healthcare research ecosystem. A framework that could serve as a foundation upon which ecosystem stakeholders can enhance the way data, information and knowledge is created, shared and used to accelerate the translation of knowledge from one area of the ecosystem to another.
-
"Eureka, Eureka!" Discoveries in Science
Agarwal, Pankaj
2011-01-01
Accidental discoveries have been of significant value in the progress of science. Although accidental discoveries are more common in pharmacology and chemistry, other branches of science have also benefited from such discoveries. While most discoveries are the result of persistent research, famous accidental discoveries provide a fascinating…
-
AM: An Artificial Intelligence Approach to Discovery in Mathematics as Heuristic Search
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
-
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...
-
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...
-
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)
-
Biomarker discovery in mass spectrometry-based urinary proteomics.
Thomas, Samuel; Hao, Ling; Ricke, William A; Li, Lingjun
2016-04-01
Urinary proteomics has become one of the most attractive topics in disease biomarker discovery. MS-based proteomic analysis has advanced continuously and emerged as a prominent tool in the field of clinical bioanalysis. However, only few protein biomarkers have made their way to validation and clinical practice. Biomarker discovery is challenged by many clinical and analytical factors including, but not limited to, the complexity of urine and the wide dynamic range of endogenous proteins in the sample. This article highlights promising technologies and strategies in the MS-based biomarker discovery process, including study design, sample preparation, protein quantification, instrumental platforms, and bioinformatics. Different proteomics approaches are discussed, and progresses in maximizing urinary proteome coverage and standardization are emphasized in this review. MS-based urinary proteomics has great potential in the development of noninvasive diagnostic assays in the future, which will require collaborative efforts between analytical scientists, systems biologists, and clinicians. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
-
Changing the Scale and Efficiency of Chemical Warfare Countermeasure Discovery Using the Zebrafish
Peterson, Randall T.; MacRae, Calum A.
2013-01-01
As the scope of potential chemical warfare agents grows rapidly and as the diversity of potential threat scenarios expands with non-state actors, so a need for innovative approaches to countermeasure development has emerged. In the last few years, the utility of the zebrafish as a model organism that is amenable to high-throughput screening has become apparent and this system has been applied to the unbiased discovery of chemical warfare countermeasures. This review summarizes the in vivo screening approach that has been pioneered in the countermeasure discovery arena, and highlights the successes to date as well as the potential challenges in moving the field forward. Importantly, the establishment of a zebrafish platform for countermeasure discovery would offer a rapid response system for the development of antidotes to the continuous stream of new potential chemical warfare agents. PMID:24273586
-
Knowledge discovery with classification rules in a cardiovascular dataset.
Podgorelec, Vili; Kokol, Peter; Stiglic, Milojka Molan; Hericko, Marjan; Rozman, Ivan
2005-12-01
In this paper we study an evolutionary machine learning approach to data mining and knowledge discovery based on the induction of classification rules. A method for automatic rules induction called AREX using evolutionary induction of decision trees and automatic programming is introduced. The proposed algorithm is applied to a cardiovascular dataset consisting of different groups of attributes which should possibly reveal the presence of some specific cardiovascular problems in young patients. A case study is presented that shows the use of AREX for the classification of patients and for discovering possible new medical knowledge from the dataset. The defined knowledge discovery loop comprises a medical expert's assessment of induced rules to drive the evolution of rule sets towards more appropriate solutions. The final result is the discovery of a possible new medical knowledge in the field of pediatric cardiology.
-
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...
-
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...
-
From crystal to compound: structure-based antimalarial drug discovery.
Drinkwater, Nyssa; McGowan, Sheena
2014-08-01
Despite a century of control and eradication campaigns, malaria remains one of the world's most devastating diseases. Our once-powerful therapeutic weapons are losing the war against the Plasmodium parasite, whose ability to rapidly develop and spread drug resistance hamper past and present malaria-control efforts. Finding new and effective treatments for malaria is now a top global health priority, fuelling an increase in funding and promoting open-source collaborations between researchers and pharmaceutical consortia around the world. The result of this is rapid advances in drug discovery approaches and technologies, with three major methods for antimalarial drug development emerging: (i) chemistry-based, (ii) target-based, and (iii) cell-based. Common to all three of these approaches is the unique ability of structural biology to inform and accelerate drug development. Where possible, SBDD (structure-based drug discovery) is a foundation for antimalarial drug development programmes, and has been invaluable to the development of a number of current pre-clinical and clinical candidates. However, as we expand our understanding of the malarial life cycle and mechanisms of resistance development, SBDD as a field must continue to evolve in order to develop compounds that adhere to the ideal characteristics for novel antimalarial therapeutics and to avoid high attrition rates pre- and post-clinic. In the present review, we aim to examine the contribution that SBDD has made to current antimalarial drug development efforts, covering hit discovery to lead optimization and prevention of parasite resistance. Finally, the potential for structural biology, particularly high-throughput structural genomics programmes, to identify future targets for drug discovery are discussed.
-
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.
-
Sassatelli, Giuseppe
2011-01-01
During the italian Risorgimento and unification periods there was a link between the idea of national unity, the exploitation of urban identities and archeology, in particular the archeology of sites belonging to inhabitance of Italy in pre-Roman times. The discoveries concerning the Etruscans particularly influenced historical events and projects related to the future of the newly unified Italy. This paper analyzes the discovery of the Etruscans in Bologna and the consequences with respect t...
-
Recent advances in inkjet dispensing technologies: applications in drug discovery.
Zhu, Xiangcheng; Zheng, Qiang; Yang, Hu; Cai, Jin; Huang, Lei; Duan, Yanwen; Xu, Zhinan; Cen, Peilin
2012-09-01
Inkjet dispensing technology is a promising fabrication methodology widely applied in drug discovery. The automated programmable characteristics and high-throughput efficiency makes this approach potentially very useful in miniaturizing the design patterns for assays and drug screening. Various custom-made inkjet dispensing systems as well as specialized bio-ink and substrates have been developed and applied to fulfill the increasing demands of basic drug discovery studies. The incorporation of other modern technologies has further exploited the potential of inkjet dispensing technology in drug discovery and development. This paper reviews and discusses the recent developments and practical applications of inkjet dispensing technology in several areas of drug discovery and development including fundamental assays of cells and proteins, microarrays, biosensors, tissue engineering, basic biological and pharmaceutical studies. Progression in a number of areas of research including biomaterials, inkjet mechanical systems and modern analytical techniques as well as the exploration and accumulation of profound biological knowledge has enabled different inkjet dispensing technologies to be developed and adapted for high-throughput pattern fabrication and miniaturization. This in turn presents a great opportunity to propel inkjet dispensing technology into drug discovery.
-
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...
-
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...
-
Computer-aided drug discovery [v1; ref status: indexed, http://f1000r.es/5ij
Directory of Open Access Journals (Sweden)
Jürgen Bajorath
2015-08-01
Full Text Available Computational approaches are an integral part of interdisciplinary drug discovery research. Understanding the science behind computational tools, their opportunities, and limitations is essential to make a true impact on drug discovery at different levels. If applied in a scientifically meaningful way, computational methods improve the ability to identify and evaluate potential drug molecules, but there remain weaknesses in the methods that preclude naïve applications. Herein, current trends in computer-aided drug discovery are reviewed, and selected computational areas are discussed. Approaches are highlighted that aid in the identification and optimization of new drug candidates. Emphasis is put on the presentation and discussion of computational concepts and methods, rather than case studies or application examples. As such, this contribution aims to provide an overview of the current methodological spectrum of computational drug discovery for a broad audience.
-
A Framework for Automatic Web Service Discovery Based on Semantics and NLP Techniques
Directory of Open Access Journals (Sweden)
Asma Adala
2011-01-01
Full Text Available As a greater number of Web Services are made available today, automatic discovery is recognized as an important task. To promote the automation of service discovery, different semantic languages have been created that allow describing the functionality of services in a machine interpretable form using Semantic Web technologies. The problem is that users do not have intimate knowledge about semantic Web service languages and related toolkits. In this paper, we propose a discovery framework that enables semantic Web service discovery based on keywords written in natural language. We describe a novel approach for automatic discovery of semantic Web services which employs Natural Language Processing techniques to match a user request, expressed in natural language, with a semantic Web service description. Additionally, we present an efficient semantic matching technique to compute the semantic distance between ontological concepts.
-
Gozalbes, Rafael; Carbajo, Rodrigo J; Pineda-Lucena, Antonio
2010-01-01
In the last decade, fragment-based drug discovery (FBDD) has evolved from a novel approach in the search of new hits to a valuable alternative to the high-throughput screening (HTS) campaigns of many pharmaceutical companies. The increasing relevance of FBDD in the drug discovery universe has been concomitant with an implementation of the biophysical techniques used for the detection of weak inhibitors, e.g. NMR, X-ray crystallography or surface plasmon resonance (SPR). At the same time, computational approaches have also been progressively incorporated into the FBDD process and nowadays several computational tools are available. These stretch from the filtering of huge chemical databases in order to build fragment-focused libraries comprising compounds with adequate physicochemical properties, to more evolved models based on different in silico methods such as docking, pharmacophore modelling, QSAR and virtual screening. In this paper we will review the parallel evolution and complementarities of biophysical techniques and computational methods, providing some representative examples of drug discovery success stories by using FBDD.
-
Application of mass spectrometry-based proteomics for biomarker discovery in neurological disorders
Directory of Open Access Journals (Sweden)
Venugopal Abhilash
2009-01-01
Full Text Available Mass spectrometry-based quantitative proteomics has emerged as a powerful approach that has the potential to accelerate biomarker discovery, both for diagnostic as well as therapeutic purposes. Proteomics has traditionally been synonymous with 2D gels but is increasingly shifting to the use of gel-free systems and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS. Quantitative proteomic approaches have already been applied to investigate various neurological disorders, especially in the context of identifying biomarkers from cerebrospinal fluid and serum. This review highlights the scope of different applications of quantitative proteomics in understanding neurological disorders with special emphasis on biomarker discovery.
-
Linked Data: Forming Partnerships at the Data Layer
Shepherd, A.; Chandler, C. L.; Arko, R. A.; Jones, M. B.; Hitzler, P.; Janowicz, K.; Krisnadhi, A.; Schildhauer, M.; Fils, D.; Narock, T.; Groman, R. C.; O'Brien, M.; Patton, E. W.; Kinkade, D.; Rauch, S.
2015-12-01
The challenges presented by big data are straining data management software architectures of the past. For smaller existing data facilities, the technical refactoring of software layers become costly to scale across the big data landscape. In response to these challenges, data facilities will need partnerships with external entities for improved solutions to perform tasks such as data cataloging, discovery and reuse, and data integration and processing with provenance. At its surface, the concept of linked open data suggests an uncalculated altruism. Yet, in his concept of five star open data, Tim Berners-Lee explains the strategic costs and benefits of deploying linked open data from the perspective of its consumer and producer - a data partnership. The Biological and Chemical Oceanography Data Management Office (BCO-DMO) addresses some of the emerging needs of its research community by partnering with groups doing complementary work and linking their respective data layers using linked open data principles. Examples will show how these links, explicit manifestations of partnerships, reduce technical debt and provide a swift flexibility for future considerations.
-
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...
-
Systems biology-embedded target validation: improving efficacy in drug discovery.
Vandamme, Drieke; Minke, Benedikt A; Fitzmaurice, William; Kholodenko, Boris N; Kolch, Walter
2014-01-01
The pharmaceutical industry is faced with a range of challenges with the ever-escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment. © 2013 Wiley Periodicals, Inc.
-
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...
-
a Web Service Approach for Linking Sensors and Cellular Spaces
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.
-
Heifetz, Alexander; Southey, Michelle; Morao, Inaki; Townsend-Nicholson, Andrea; Bodkin, Mike J
2018-01-01
GPCR modeling approaches are widely used in the hit-to-lead (H2L) and lead optimization (LO) stages of drug discovery. The aims of these modeling approaches are to predict the 3D structures of the receptor-ligand complexes, to explore the key interactions between the receptor and the ligand and to utilize these insights in the design of new molecules with improved binding, selectivity or other pharmacological properties. In this book chapter, we present a brief survey of key computational approaches integrated with hierarchical GPCR modeling protocol (HGMP) used in hit-to-lead (H2L) and in lead optimization (LO) stages of structure-based drug discovery (SBDD). We outline the differences in modeling strategies used in H2L and LO of SBDD and illustrate how these tools have been applied in three drug discovery projects.
-
Accelerating the discovery of materials for clean energy in the era of smart automation
Tabor, Daniel P.; Roch, Loïc M.; Saikin, Semion K.; Kreisbeck, Christoph; Sheberla, Dennis; Montoya, Joseph H.; Dwaraknath, Shyam; Aykol, Muratahan; Ortiz, Carlos; Tribukait, Hermann; Amador-Bedolla, Carlos; Brabec, Christoph J.; Maruyama, Benji; Persson, Kristin A.; Aspuru-Guzik, Alán
2018-05-01
The discovery and development of novel materials in the field of energy are essential to accelerate the transition to a low-carbon economy. Bringing recent technological innovations in automation, robotics and computer science together with current approaches in chemistry, materials synthesis and characterization will act as a catalyst for revolutionizing traditional research and development in both industry and academia. This Perspective provides a vision for an integrated artificial intelligence approach towards autonomous materials discovery, which, in our opinion, will emerge within the next 5 to 10 years. The approach we discuss requires the integration of the following tools, which have already seen substantial development to date: high-throughput virtual screening, automated synthesis planning, automated laboratories and machine learning algorithms. In addition to reducing the time to deployment of new materials by an order of magnitude, this integrated approach is expected to lower the cost associated with the initial discovery. Thus, the price of the final products (for example, solar panels, batteries and electric vehicles) will also decrease. This in turn will enable industries and governments to meet more ambitious targets in terms of reducing greenhouse gas emissions at a faster pace.
-
Enzymatic cellulose oxidation is linked to lignin by long-range electron transfer
DEFF Research Database (Denmark)
Westereng, Bjorge; Cannella, David; Wittrup Agger, Jane
2015-01-01
cell walls. Electron transfer was confirmed by electron paramagnetic resonance spectroscopy showing that LPMO activity on cellulose changes the level of unpaired electrons in the lignin. The discovery of a long-range electron transfer mechanism links the biodegradation of cellulose and lignin and sheds...
-
De Novo Discovery of Structured ncRNA Motifs in Genomic Sequences
DEFF Research Database (Denmark)
Ruzzo, Walter L; Gorodkin, Jan
2014-01-01
De novo discovery of "motifs" capturing the commonalities among related noncoding ncRNA structured RNAs is among the most difficult problems in computational biology. This chapter outlines the challenges presented by this problem, together with some approaches towards solving them, with an emphas...... on an approach based on the CMfinder CMfinder program as a case study. Applications to genomic screens for novel de novo structured ncRNA ncRNA s, including structured RNA elements in untranslated portions of protein-coding genes, are presented.......De novo discovery of "motifs" capturing the commonalities among related noncoding ncRNA structured RNAs is among the most difficult problems in computational biology. This chapter outlines the challenges presented by this problem, together with some approaches towards solving them, with an emphasis...
-
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.
-
Anthelmintics: From discovery to resistance II (San Diego, 2016
Directory of Open Access Journals (Sweden)
Richard J. Martin
2016-12-01
Full Text Available The second scientific meeting in the series: “Anthelmintics: From Discovery to Resistance” was held in San Diego in February, 2016. The focus topics of the meeting, related to anthelmintic discovery and resistance, were novel technologies, bioinformatics, commercial interests, anthelmintic modes of action and anthelmintic resistance. Basic scientific, human and veterinary interests were addressed in oral and poster presentations. The delegates were from universities and industries in the US, Europe, Australia and New Zealand. The papers were a great representation of the field, and included the use of C. elegans for lead discovery, mechanisms of anthelmintic resistance, nematode neuropeptides, proteases, B. thuringiensis crystal protein, nicotinic receptors, emodepside, benzimidazoles, P-glycoproteins, natural products, microfluidic techniques and bioinformatics approaches. The NIH also presented NIAID-specific parasite genomic priorities and initiatives. From these papers we introduce below selected papers with a focus on anthelmintic drug screening and development.
-
Usability of Discovery Portals
Bulens, J.D.; Vullings, L.A.E.; Houtkamp, J.M.; Vanmeulebrouk, B.
2013-01-01
As INSPIRE progresses to be implemented in the EU, many new discovery portals are built to facilitate finding spatial data. Currently the structure of the discovery portals is determined by the way spatial data experts like to work. However, we argue that the main target group for discovery portals are not spatial data experts but professionals with limited spatial knowledge, and a focus outside the spatial domain. An exploratory usability experiment was carried out in which three discovery p...
-
Price Discovery from Cross-Currency and FX Swaps: A Structural Analysis
Yasuaki Amatatsu; Naohiko Baba
2007-01-01
This paper investigates the relative role of price discovery between two long-term swap contracts that exchange between the U.S. dollar and the Japanese yen: cross-currency basis swap and FX (foreign exchange) swap. First, we show that these two swaps should be in a no-arbitrage relationship by allowing for differential risk premiums. Second, we empirically investigate the relative role of price discovery using the structural-form approach based on the state space models. Main finding are as ...
-
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).
-
2010-04-01
... 19 Customs Duties 3 2010-04-01 2010-04-01 false Discovery. 354.10 Section 354.10 Customs Duties... ANTIDUMPING OR COUNTERVAILING DUTY ADMINISTRATIVE PROTECTIVE ORDER § 354.10 Discovery. (a) Voluntary discovery. All parties are encouraged to engage in voluntary discovery procedures regarding any matter, not...
-
2010-07-01
... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Discovery. 1150.63 Section... PRACTICE AND PROCEDURES FOR COMPLIANCE HEARINGS Prehearing Conferences and Discovery § 1150.63 Discovery. (a) Parties are encouraged to engage in voluntary discovery procedures. For good cause shown under...
-
2010-07-01
... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Discovery. 11.52 Section 11... Disciplinary Proceedings; Jurisdiction, Sanctions, Investigations, and Proceedings § 11.52 Discovery. Discovery... establishes that discovery is reasonable and relevant, the hearing officer, under such conditions as he or she...
-
Fragment-based drug discovery using rational design.
Jhoti, H
2007-01-01
Fragment-based drug discovery (FBDD) is established as an alternative approach to high-throughput screening for generating novel small molecule drug candidates. In FBDD, relatively small libraries of low molecular weight compounds (or fragments) are screened using sensitive biophysical techniques to detect their binding to the target protein. A lower absolute affinity of binding is expected from fragments, compared to much higher molecular weight hits detected by high-throughput screening, due to their reduced size and complexity. Through the use of iterative cycles of medicinal chemistry, ideally guided by three-dimensional structural data, it is often then relatively straightforward to optimize these weak binding fragment hits into potent and selective lead compounds. As with most other lead discovery methods there are two key components of FBDD; the detection technology and the compound library. In this review I outline the two main approaches used for detecting the binding of low affinity fragments and also some of the key principles that are used to generate a fragment library. In addition, I describe an example of how FBDD has led to the generation of a drug candidate that is now being tested in clinical trials for the treatment of cancer.
-
Therapeutics discovery: From bench to first in-human trials.
Al-Hujaily, Ensaf M; Khatlani, Tanvir; Alehaideb, Zeyad; Ali, Rizwan; Almuzaini, Bader; Alrfaei, Bahauddeen M; Iqbal, Jahangir; Islam, Imadul; Malik, Shuja; Marwani, Bader A; Massadeh, Salam; Nehdi, Atef; Alsomaie, Barrak; Debasi, Bader; Bushnak, Ibraheem; Noibi, Saeed; Hussain, Syed; Wajid, Wahid Abdul; Armand, Jean-Pierre; Gul, Sheraz; Oyarzabal, Julen; Rais, Rana; Bountra, Chas; Alaskar, Ahmed; Knawy, Bander Al; Boudjelal, Mohamed
2018-03-01
The 'Therapeutics discovery: From bench to first in-human trials' conference, held at the King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), Kingdom of Saudi Arabia (KSA) from October 10-12, 2017, provided a unique opportunity for experts worldwide to discuss advances in drug discovery and development, focusing on phase I clinical trials. It was the first event of its kind to be hosted at the new research center, which was constructed to boost drug discovery and development in the KSA in collaboration with institutions, such as the Academic Drug Discovery Consortium in the United States of America (USA), Structural Genomics Consortium of the University of Oxford in the United Kingdom (UK), and Institute of Materia Medica of the Chinese Academy of Medical Sciences in China. The program was divided into two parts. A pre-symposium day took place on October 10, during which courses were conducted on clinical trials, preclinical drug discovery, molecular biology and nanofiber research. The attendees had the opportunity for one-to-one meetings with international experts to exchange information and foster collaborations. In the second part of the conference, which took place on October 11 and 12, the clinical trials pipeline, design and recruitment of volunteers, and economic impact of clinical trials were discussed. The Saudi Food and Drug Administration presented the regulations governing clinical trials in the KSA. The process of preclinical drug discovery from small molecules, cellular and immunologic therapies, and approaches to identifying new targets were also presented. The recommendation of the conference was that researchers in the KSA must invest more fund, talents and infrastructure to lead the region in phase I clinical trials and preclinical drug discovery. Diseases affecting the local population, such as Middle East Respiratory Syndrome and resistant bacterial infections, represent the optimal
-
Usability of Discovery Portals
Bulens, J.D.; Vullings, L.A.E.; Houtkamp, J.M.; Vanmeulebrouk, B.
2013-01-01
As INSPIRE progresses to be implemented in the EU, many new discovery portals are built to facilitate finding spatial data. Currently the structure of the discovery portals is determined by the way spatial data experts like to work. However, we argue that the main target group for discovery portals
-
2010-01-01
... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Discovery. 16.213 Section 16.213... PRACTICE FOR FEDERALLY-ASSISTED AIRPORT ENFORCEMENT PROCEEDINGS Hearings § 16.213 Discovery. (a) Discovery... discovery permitted by this section if a party shows that— (1) The information requested is cumulative or...
-
2010-07-01
... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Discovery. 76.21 Section 76.21 Judicial... POSSESSION OF CERTAIN CONTROLLED SUBSTANCES § 76.21 Discovery. (a) Scope. Discovery under this part covers... as a general guide for discovery practices in proceedings before the Judge. However, unless otherwise...
-
Planetary Science Research Discoveries (PSRD) www.psrd.hawaii.edu
Martel, L.; Taylor, J.
2010-12-01
NASA's Year of the Solar System is celebrating not only Solar System mission milestones but also the collective data reduction and analysis that happens here on Earth. The Cosmochemistry Program of NASA's Science Mission Directorate takes a direct approach to enhance student learning and engage the public in the latest research on meteorites, asteroids, planets, moons, and other materials in our Solar System with the website known as PSRD. The Planetary Science Research Discoveries (PSRD) website at www.psrd.hawaii.edu explores the science questions that researchers are actively pursuing about our Solar System and explains how the answers are discovered and what they mean. The site helps to convey the scientific basis for sample study to the broader scientific community and the excitement of new results in cosmochemistry to the general public. We share with our broad audience the fascinating discoveries made by cosmochemists, increasing public awareness of the value of sample-focused research in particular and of fundamental scientific research and space exploration in general. The scope of the website covers the full range of cosmochemical research and highlights the investigations of extraterrestrial materials that are used to better understand the origin of the Solar System and the processes by which planets, moons, and small bodies evolve. We relate the research to broader planetary science themes and mission results. Articles are categorized into: asteroids, comets, Earth, instruments of cosmochemistry, Jupiter system, Mars, Mars life issues, Mercury, meteorites, Moon, origins, and space weathering. PSRD articles are based on peer-reviewed, journal publications. Some PSRD articles are based on more than one published paper in order to present multiple views and outcomes of research on a topic of interest. To date, 150 PSRD articles have been based on 184 journal articles (and counting) written by some of the most active cosmochemists and planetary scientists
-
A semantic-based approach for querying linked data using natural language
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.
-
A semantic-based approach for querying linked data using natural language
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.
-
Metabolomics for Biomarker Discovery: Moving to the Clinic
Zhang, Aihua; Sun, Hui; Yan, Guangli; Wang, Ping; Wang, Xijun
2015-01-01
To improve the clinical course of diseases, more accurate diagnostic and assessment methods are required as early as possible. In order to achieve this, metabolomics offers new opportunities for biomarker discovery in complex diseases and may provide pathological understanding of diseases beyond traditional technologies. It is the systematic analysis of low-molecular-weight metabolites in biological samples and has become an important tool in clinical research and the diagnosis of human disease and has been applied to discovery and identification of the perturbed pathways. It provides a powerful approach to discover biomarkers in biological systems and offers a holistic approach with the promise to clinically enhance diagnostics. When carried out properly, it could provide insight into the understanding of the underlying mechanisms of diseases, help to identify patients at risk of disease, and predict the response to specific treatments. Currently, metabolomics has become an important tool in clinical research and the diagnosis of human disease and becomes a hot topic. This review will highlight the importance and benefit of metabolomics for identifying biomarkers that accurately screen potential biomarkers of diseases. PMID:26090402
-
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...
-
2010-07-01
... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Discovery. 41.150 Section 41... COMMERCE PRACTICE BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES Contested Cases § 41.150 Discovery. (a) Limited discovery. A party is not entitled to discovery except as authorized in this subpart. The...
-
2010-01-01
... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Discovery. 13.220 Section 13.220... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Rules of Practice in FAA Civil Penalty Actions § 13.220 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or...
-
2010-10-01
... 49 Transportation 7 2010-10-01 2010-10-01 false Discovery. 604.38 Section 604.38 Transportation... TRANSPORTATION CHARTER SERVICE Hearings. § 604.38 Discovery. (a) Permissible forms of discovery shall be within the discretion of the PO. (b) The PO shall limit the frequency and extent of discovery permitted by...
-
2010-01-01
... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 719.10 Section 719.10... Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter... the Federal Rules of Civil Procedure relating to discovery apply to the extent consistent with this...
-
2010-04-01
... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 26.18 Section 26.18... PROCEDURES Hearings Before Hearing Officers Discovery § 26.18 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery procedures, which may commence at any time after an answer has...
-
2010-10-01
... 42 Public Health 3 2010-10-01 2010-10-01 false Discovery. 426.532 Section 426.532 Public Health... § 426.532 Discovery. (a) General rule. If the Board orders discovery, the Board must establish a reasonable timeframe for discovery. (b) Protective order—(1) Request for a protective order. Any party...
-
2010-10-01
... 49 Transportation 9 2010-10-01 2010-10-01 false Discovery. 1503.633 Section 1503.633... Rules of Practice in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or approval of the ALJ, at...
-
2010-01-01
... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Discovery. 1264.120 Section 1264.120... PENALTIES ACT OF 1986 § 1264.120 Discovery. (a) The following types of discovery are authorized: (1..., discovery is available only as ordered by the presiding officer. The presiding officer shall regulate the...
-
2010-04-01
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 128.6 Section 128.6 Foreign... Discovery. (a) Discovery by the respondent. The respondent, through the Administrative Law Judge, may... discovery if the interests of national security or foreign policy so require, or if necessary to comply with...
-
2010-04-01
... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 26.42 Section 26.42... PROCEDURES Hearings Pursuant to the Administrative Procedure Act Discovery § 26.42 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery procedures, which may commence at any time...
-
2010-10-01
... 49 Transportation 5 2010-10-01 2010-10-01 false Discovery. 386.37 Section 386.37 Transportation... and Hearings § 386.37 Discovery. (a) Parties may obtain discovery by one or more of the following...; and requests for admission. (b) Discovery may not commence until the matter is pending before the...
-
2010-07-01
... 29 Labor 9 2010-07-01 2010-07-01 false Discovery. 1955.32 Section 1955.32 Labor Regulations...) PROCEDURES FOR WITHDRAWAL OF APPROVAL OF STATE PLANS Preliminary Conference and Discovery § 1955.32 Discovery... allow discovery by any other appropriate procedure, such as by interrogatories upon a party or request...
-
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
-
Object-graphs for context-aware visual category discovery.
Lee, Yong Jae; Grauman, Kristen
2012-02-01
How can knowing about some categories help us to discover new ones in unlabeled images? Unsupervised visual category discovery is useful to mine for recurring objects without human supervision, but existing methods assume no prior information and thus tend to perform poorly for cluttered scenes with multiple objects. We propose to leverage knowledge about previously learned categories to enable more accurate discovery, and address challenges in estimating their familiarity in unsegmented, unlabeled images. We introduce two variants of a novel object-graph descriptor to encode the 2D and 3D spatial layout of object-level co-occurrence patterns relative to an unfamiliar region and show that by using them to model the interaction between an image’s known and unknown objects, we can better detect new visual categories. Rather than mine for all categories from scratch, our method identifies new objects while drawing on useful cues from familiar ones. We evaluate our approach on several benchmark data sets and demonstrate clear improvements in discovery over conventional purely appearance-based baselines.
-
Motivating Communities To Go Beyond the Discovery Plateau
Habermann, T.; Kozimor, J.
2014-12-01
Years of emphasizing discovery and minimal metadata requirements have resulted in a culture that accepts that metadata are for discovery and complete metadata are too complex or difficult for researchers to understand and create. Evolving the culture past this "data-discovery plateau" requires a multi-faceted approach that addresses the rational and emotional sides of the problem. On the rational side, scientists know that data and results must be well documented in order to be reproducible, re-usable, and trustworthy. We need tools that script critical moves towards well-described destinations and help identify members of the community that are already leading the way towards those destinations. We need mechanisms that help those leaders share their experiences and examples. On the emotional side, we need to emphasize that high-quality metadata makes data trustworthy, divide the improvement process into digestible pieces and create mechanisms for clearly identifying and rewarding progress. We also need to provide clear opportunities for community members to increase their expertise and to share their skills.
-
Targeting cysteine proteases in trypanosomatid disease drug discovery.
Ferreira, Leonardo G; Andricopulo, Adriano D
2017-12-01
Chagas disease and human African trypanosomiasis are endemic conditions in Latin America and Africa, respectively, for which no effective and safe therapy is available. Efforts in drug discovery have focused on several enzymes from these protozoans, among which cysteine proteases have been validated as molecular targets for pharmacological intervention. These enzymes are expressed during the entire life cycle of trypanosomatid parasites and are essential to many biological processes, including infectivity to the human host. As a result of advances in the knowledge of the structural aspects of cysteine proteases and their role in disease physiopathology, inhibition of these enzymes by small molecules has been demonstrated to be a worthwhile approach to trypanosomatid drug research. This review provides an update on drug discovery strategies targeting the cysteine peptidases cruzain from Trypanosoma cruzi and rhodesain and cathepsin B from Trypanosoma brucei. Given that current chemotherapy for Chagas disease and human African trypanosomiasis has several drawbacks, cysteine proteases will continue to be actively pursued as valuable molecular targets in trypanosomatid disease drug discovery efforts. Copyright © 2017. Published by Elsevier Inc.
-
Organic synthesis provides opportunities to transform drug discovery
Blakemore, David C.; Castro, Luis; Churcher, Ian; Rees, David C.; Thomas, Andrew W.; Wilson, David M.; Wood, Anthony
2018-03-01
Despite decades of ground-breaking research in academia, organic synthesis is still a rate-limiting factor in drug-discovery projects. Here we present some current challenges in synthetic organic chemistry from the perspective of the pharmaceutical industry and highlight problematic steps that, if overcome, would find extensive application in the discovery of transformational medicines. Significant synthesis challenges arise from the fact that drug molecules typically contain amines and N-heterocycles, as well as unprotected polar groups. There is also a need for new reactions that enable non-traditional disconnections, more C-H bond activation and late-stage functionalization, as well as stereoselectively substituted aliphatic heterocyclic ring synthesis, C-X or C-C bond formation. We also emphasize that syntheses compatible with biomacromolecules will find increasing use, while new technologies such as machine-assisted approaches and artificial intelligence for synthesis planning have the potential to dramatically accelerate the drug-discovery process. We believe that increasing collaboration between academic and industrial chemists is crucial to address the challenges outlined here.
-
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...
-
2010-01-01
... 10 Energy 1 2010-01-01 2010-01-01 false Discovery. 13.21 Section 13.21 Energy NUCLEAR REGULATORY COMMISSION PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) The following types of discovery are...) Unless mutually agreed to by the parties, discovery is available only as ordered by the ALJ. The ALJ...
-
2010-10-01
... 49 Transportation 8 2010-10-01 2010-10-01 false Discovery. 1121.2 Section 1121.2 Transportation... TRANSPORTATION RULES OF PRACTICE RAIL EXEMPTION PROCEDURES § 1121.2 Discovery. Discovery shall follow the procedures set forth at 49 CFR part 1114, subpart B. Discovery may begin upon the filing of the petition for...
-
2010-07-01
... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Discovery. 42.21 Section... IMPLEMENTING THE PROGRAM FRAUD CIVIL REMEDIES ACT § 42.21 Discovery. (a) The following types of discovery are... creation of a document. (c) Unless mutually agreed to by the parties, discovery is available only as...
-
2010-04-01
... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Discovery. 521.21 Section 521.21 Foreign... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for... interpreted to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery is...
-
2010-07-01
... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Discovery. 10.71 Section 10.71 Money... SERVICE Rules Applicable to Disciplinary Proceedings § 10.71 Discovery. (a) In general. Discovery may be... relevance, materiality and reasonableness of the requested discovery and subject to the requirements of § 10...
-
2010-07-01
... 39 Postal Service 1 2010-07-01 2010-07-01 false Discovery. 955.15 Section 955.15 Postal Service... APPEALS § 955.15 Discovery. (a) The parties are encouraged to engage in voluntary discovery procedures. In connection with any deposition or other discovery procedure, the Board may issue any order which justice...
-
2010-10-01
... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discovery. 35.21 Section 35.21 Public... AND STATEMENTS § 35.21 Discovery. (a) The following types of discovery are authorized: (1) Requests...) Unless mutually agreed to by the parties, discovery is available only as ordered by the ALJ. The ALJ...
-
2010-01-01
... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 766.9 Section 766.9... PROCEEDINGS § 766.9 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery... provisions of the Federal Rules of Civil Procedure relating to discovery apply to the extent consistent with...
-
Materializing the web of linked data
Konstantinou, Nikolaos
2015-01-01
This book explains the Linked Data domain by adopting a bottom-up approach: it introduces the fundamental Semantic Web technologies and building blocks, which are then combined into methodologies and end-to-end examples for publishing datasets as Linked Data, and use cases that harness scholarly information and sensor data. It presents how Linked Data is used for web-scale data integration, information management and search. Special emphasis is given to the publication of Linked Data from relational databases as well as from real-time sensor data streams. The authors also trace the transformation from the document-based World Wide Web into a Web of Data. Materializing the Web of Linked Data is addressed to researchers and professionals studying software technologies, tools and approaches that drive the Linked Data ecosystem, and the Web in general.
-
Get Involved in Planetary Discoveries through New Worlds, New Discoveries
Shupla, Christine; Shipp, S. S.; Halligan, E.; Dalton, H.; Boonstra, D.; Buxner, S.; SMD Planetary Forum, NASA
2013-01-01
"New Worlds, New Discoveries" is a synthesis of NASA’s 50-year exploration history which provides an integrated picture of our new understanding of our solar system. As NASA spacecraft head to and arrive at key locations in our solar system, "New Worlds, New Discoveries" provides an integrated picture of our new understanding of the solar system to educators and the general public! The site combines the amazing discoveries of past NASA planetary missions with the most recent findings of ongoing missions, and connects them to the related planetary science topics. "New Worlds, New Discoveries," which includes the "Year of the Solar System" and the ongoing celebration of the "50 Years of Exploration," includes 20 topics that share thematic solar system educational resources and activities, tied to the national science standards. This online site and ongoing event offers numerous opportunities for the science community - including researchers and education and public outreach professionals - to raise awareness, build excitement, and make connections with educators, students, and the public about planetary science. Visitors to the site will find valuable hands-on science activities, resources and educational materials, as well as the latest news, to engage audiences in planetary science topics and their related mission discoveries. The topics are tied to the big questions of planetary science: how did the Sun’s family of planets and bodies originate and how have they evolved? How did life begin and evolve on Earth, and has it evolved elsewhere in our solar system? Scientists and educators are encouraged to get involved either directly or by sharing "New Worlds, New Discoveries" and its resources with educators, by conducting presentations and events, sharing their resources and events to add to the site, and adding their own public events to the site’s event calendar! Visit to find quality resources and ideas. Connect with educators, students and the public to
-
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...
-
2010-07-01
... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Discovery. 16.21 Section 16.21 Money... FRAUD CIVIL REMEDIES ACT OF 1986 § 16.21 Discovery. (a) The following types of discovery are authorized... to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery is...
-
Controlling the Rate of GWAS False Discoveries.
Brzyski, Damian; Peterson, Christine B; Sobczyk, Piotr; Candès, Emmanuel J; Bogdan, Malgorzata; Sabatti, Chiara
2017-01-01
With the rise of both the number and the complexity of traits of interest, control of the false discovery rate (FDR) in genetic association studies has become an increasingly appealing and accepted target for multiple comparison adjustment. While a number of robust FDR-controlling strategies exist, the nature of this error rate is intimately tied to the precise way in which discoveries are counted, and the performance of FDR-controlling procedures is satisfactory only if there is a one-to-one correspondence between what scientists describe as unique discoveries and the number of rejected hypotheses. The presence of linkage disequilibrium between markers in genome-wide association studies (GWAS) often leads researchers to consider the signal associated to multiple neighboring SNPs as indicating the existence of a single genomic locus with possible influence on the phenotype. This a posteriori aggregation of rejected hypotheses results in inflation of the relevant FDR. We propose a novel approach to FDR control that is based on prescreening to identify the level of resolution of distinct hypotheses. We show how FDR-controlling strategies can be adapted to account for this initial selection both with theoretical results and simulations that mimic the dependence structure to be expected in GWAS. We demonstrate that our approach is versatile and useful when the data are analyzed using both tests based on single markers and multiple regression. We provide an R package that allows practitioners to apply our procedure on standard GWAS format data, and illustrate its performance on lipid traits in the North Finland Birth Cohort 66 cohort study. Copyright © 2017 by the Genetics Society of America.
-
NASA Reverb: Standards-Driven Earth Science Data and Service Discovery
Cechini, M. F.; Mitchell, A.; Pilone, D.
2011-12-01
. After a yearlong design, development, and testing process, the ECHO team successfully released "Reverb - The Next Generation Earth Science Discovery Tool." Reverb relies heavily on the information contained in dataset and granule metadata, such as ISO 19115, to provide a dynamic experience to users based on identified search facet values extracted from science metadata. Such an approach allows users to perform cross-dataset correlation and searches, discovering additional data that they may not previously have been aware of. In addition to data discovery, Reverb users may discover services associated with their data of interest. When services utilize supported standards and/or protocols, Reverb can facilitate the invocation of both synchronous and asynchronous data processing services. This greatly enhances a users ability to discover data of interest and accomplish their research goals. Extrapolating on the current movement towards interoperable standards and an increase in available services, data service invocation and chaining will become a natural part of data discovery. Reverb is one example of a discovery tool that provides a mechanism for transforming the earth science data discovery paradigm.
-
Proteome analysis of body fluids for amyotrophic lateral sclerosis biomarker discovery.
Krüger, Thomas; Lautenschläger, Janin; Grosskreutz, Julian; Rhode, Heidrun
2013-01-01
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of motor neurons leading to death of the patients, mostly within 2-5 years after disease onset. The pathomechanism of motor neuron degeneration is only partially understood and therapeutic strategies based on mechanistic insights are largely ineffective. The discovery of reliable biomarkers of disease diagnosis and progression is the sine qua non of both the revelation of insights into the ALS pathomechanism and the assessment of treatment efficacies. Proteomic approaches are an important pillar in ALS biomarker discovery. Cerebrospinal fluid is the most promising body fluid for differential proteome analyses, followed by blood (serum, plasma), and even urine and saliva. The present study provides an overview about reported peptide/protein biomarker candidates that showed significantly altered levels in certain body fluids of ALS patients. These findings have to be discussed according to proposed pathomechanisms to identify modifiers of disease progression and to pave the way for the development of potential therapeutic strategies. Furthermore, limitations and advantages of proteomic approaches for ALS biomarker discovery in different body fluids and reliable validation of biomarker candidates have been addressed. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
-
Discovery and Selection of Semantic Web Services
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...
-
Recent development in software and automation tools for high-throughput discovery bioanalysis.
Shou, Wilson Z; Zhang, Jun
2012-05-01
Bioanalysis with LC-MS/MS has been established as the method of choice for quantitative determination of drug candidates in biological matrices in drug discovery and development. The LC-MS/MS bioanalytical support for drug discovery, especially for early discovery, often requires high-throughput (HT) analysis of large numbers of samples (hundreds to thousands per day) generated from many structurally diverse compounds (tens to hundreds per day) with a very quick turnaround time, in order to provide important activity and liability data to move discovery projects forward. Another important consideration for discovery bioanalysis is its fit-for-purpose quality requirement depending on the particular experiments being conducted at this stage, and it is usually not as stringent as those required in bioanalysis supporting drug development. These aforementioned attributes of HT discovery bioanalysis made it an ideal candidate for using software and automation tools to eliminate manual steps, remove bottlenecks, improve efficiency and reduce turnaround time while maintaining adequate quality. In this article we will review various recent developments that facilitate automation of individual bioanalytical procedures, such as sample preparation, MS/MS method development, sample analysis and data review, as well as fully integrated software tools that manage the entire bioanalytical workflow in HT discovery bioanalysis. In addition, software tools supporting the emerging high-resolution accurate MS bioanalytical approach are also discussed.
-
Chemogenomic discovery of allosteric antagonists at the GPRC6A receptor
DEFF Research Database (Denmark)
Gloriam, David E.; Wellendorph, Petrine; Johansen, Lars Dan
2011-01-01
and pharmacological character: (1) chemogenomic lead identification through the first, to our knowledge, ligand inference between two different GPCR families, Families A and C; and (2) the discovery of the most selective GPRC6A allosteric antagonists discovered to date. The unprecedented inference of...... pharmacological activity across GPCR families provides proof-of-concept for in silico approaches against Family C targets based on Family A templates, greatly expanding the prospects of successful drug design and discovery. The antagonists were tested against a panel of seven Family A and C G protein-coupled receptors...
-
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.
-
Energy Efficient Link Aware Routing with Power Control in Wireless Ad Hoc Networks.
Katiravan, Jeevaa; Sylvia, D; Rao, D Srinivasa
2015-01-01
In wireless ad hoc networks, the traditional routing protocols make the route selection based on minimum distance between the nodes and the minimum number of hop counts. Most of the routing decisions do not consider the condition of the network such as link quality and residual energy of the nodes. Also, when a link failure occurs, a route discovery mechanism is initiated which incurs high routing overhead. If the broadcast nature and the spatial diversity of the wireless communication are utilized efficiently it becomes possible to achieve improvement in the performance of the wireless networks. In contrast to the traditional routing scheme which makes use of a predetermined route for packet transmission, such an opportunistic routing scheme defines a predefined forwarding candidate list formed by using single network metrics. In this paper, a protocol is proposed which uses multiple metrics such as residual energy and link quality for route selection and also includes a monitoring mechanism which initiates a route discovery for a poor link, thereby reducing the overhead involved and improving the throughput of the network while maintaining network connectivity. Power control is also implemented not only to save energy but also to improve the network performance. Using simulations, we show the performance improvement attained in the network in terms of packet delivery ratio, routing overhead, and residual energy of the network.
-
Energy Efficient Link Aware Routing with Power Control in Wireless Ad Hoc Networks
Directory of Open Access Journals (Sweden)
Jeevaa Katiravan
2015-01-01
Full Text Available In wireless ad hoc networks, the traditional routing protocols make the route selection based on minimum distance between the nodes and the minimum number of hop counts. Most of the routing decisions do not consider the condition of the network such as link quality and residual energy of the nodes. Also, when a link failure occurs, a route discovery mechanism is initiated which incurs high routing overhead. If the broadcast nature and the spatial diversity of the wireless communication are utilized efficiently it becomes possible to achieve improvement in the performance of the wireless networks. In contrast to the traditional routing scheme which makes use of a predetermined route for packet transmission, such an opportunistic routing scheme defines a predefined forwarding candidate list formed by using single network metrics. In this paper, a protocol is proposed which uses multiple metrics such as residual energy and link quality for route selection and also includes a monitoring mechanism which initiates a route discovery for a poor link, thereby reducing the overhead involved and improving the throughput of the network while maintaining network connectivity. Power control is also implemented not only to save energy but also to improve the network performance. Using simulations, we show the performance improvement attained in the network in terms of packet delivery ratio, routing overhead, and residual energy of the network.
-
Biomarker discovery for colon cancer using a 761 gene RT-PCR assay
Directory of Open Access Journals (Sweden)
Hackett James R
2007-08-01
Full Text Available Abstract Background Reverse transcription PCR (RT-PCR is widely recognized to be the gold standard method for quantifying gene expression. Studies using RT-PCR technology as a discovery tool have historically been limited to relatively small gene sets compared to other gene expression platforms such as microarrays. We have recently shown that TaqMan® RT-PCR can be scaled up to profile expression for 192 genes in fixed paraffin-embedded (FPE clinical study tumor specimens. This technology has also been used to develop and commercialize a widely used clinical test for breast cancer prognosis and prediction, the Onco typeDX™ assay. A similar need exists in colon cancer for a test that provides information on the likelihood of disease recurrence in colon cancer (prognosis and the likelihood of tumor response to standard chemotherapy regimens (prediction. We have now scaled our RT-PCR assay to efficiently screen 761 biomarkers across hundreds of patient samples and applied this process to biomarker discovery in colon cancer. This screening strategy remains attractive due to the inherent advantages of maintaining platform consistency from discovery through clinical application. Results RNA was extracted from formalin fixed paraffin embedded (FPE tissue, as old as 28 years, from 354 patients enrolled in NSABP C-01 and C-02 colon cancer studies. Multiplexed reverse transcription reactions were performed using a gene specific primer pool containing 761 unique primers. PCR was performed as independent TaqMan® reactions for each candidate gene. Hierarchal clustering demonstrates that genes expected to co-express form obvious, distinct and in certain cases very tightly correlated clusters, validating the reliability of this technical approach to biomarker discovery. Conclusion We have developed a high throughput, quantitatively precise multi-analyte gene expression platform for biomarker discovery that approaches low density DNA arrays in numbers of
-
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)
-
LinkED: A Novel Methodology for Publishing Linked Enterprise Data
Directory of Open Access Journals (Sweden)
Shreyas Suresh Rao
2017-01-01
Full Text Available Semantic Web technologies have redefined and strengthened the Enterprise-Web interoperability over the last decade. Linked Open Data (LOD refers to a set of best practices that empower enterprises to publish and interlink their data using existing ontologies on the World Wide Web. Current research in LOD focuses on expert search, the creation of unified information space and augmentation of core data from an enterprise context. However, existing approaches for publication of enterprise data as LOD are domain-specific, ad-hoc and suffer from lack of uniform representation across domains. The paper proposes a novel methodology called LinkED that contributes towards LOD literature in two ways: (a streamlines the publishing process through five stages of cleaning, triplification, interlinking, storage and visualization; (b addresses the latest challenges in LOD publication, namely: inadequate links, inconsistencies in the quality of the dataset and replicability of the LOD publication process. Further, the methodology is demonstrated via the publication of digital repository data as LOD in a university setting, which is evaluated based on two semantic standards: Five-Star model and data quality metrics. Overall, the paper provides a generic LOD publication process that is applicable across various domains such as healthcare, e-governance, banking, and tourism, to name a few.
-
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)
-
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.
-
29 CFR 2700.56 - Discovery; general.
2010-07-01
...(c) or 111 of the Act has been filed. 30 U.S.C. 815(c) and 821. (e) Completion of discovery... 29 Labor 9 2010-07-01 2010-07-01 false Discovery; general. 2700.56 Section 2700.56 Labor... Hearings § 2700.56 Discovery; general. (a) Discovery methods. Parties may obtain discovery by one or more...
-
Discovery and preclinical development of new antibiotics.
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.
-
Directory of Open Access Journals (Sweden)
Hendra Erik Rudyanto
2016-11-01
Full Text Available This Study aims to produce a model learning device discovery learning with scientific approach to improve the character charged valid creative thinking, practical and effective. The model refers to a model of learning development includes activities Plomp initial investigation, design, realization/contruction, testing, evaluation and revision. The results showed that (1 learning tools developed valid; syllabus ehit an average of 3,3 (very good; RPP with an average of 3,2 (good; LKS with an average of 3,2 (good; textbook student with an average of 3,3 (very good; and TKBK with an average of 3,5 (good.; (2 the stated learning practical , namely: 1 the activity of student on both criteria, an average score 74,1%; 2 the activity of the teacher are very good on the criterion, the average score of 98,25; 3 positive teacher response, a score of 97,14; 4 positive students response, average 89,73.; (3 the learning of mathematics is declared effective the indicator 1 traffic to think creatively achieve mastery with the average value of 71,55 and a classical completeness reaches 90%; 2 the average grade of creative thinking ability model of discovery learning with scientific approachis better than ekspositori class; 3 the character of the curiosity and skills to communicate a positive influence on the ability to think creatively; and 4 an increase in the ability to think creatively in class models discovery learning with scientific approach. Keywords: discovery learning, scientific approach, creative thinking ability.
-
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
-
SECURE SERVICE DISCOVERY BASED ON PROBE PACKET MECHANISM FOR MANETS
Directory of Open Access Journals (Sweden)
S. Pariselvam
2015-03-01
Full Text Available In MANETs, Service discovery process is always considered to be crucial since they do not possess a centralized infrastructure for communication. Moreover, different services available through the network necessitate varying categories. Hence, a need arises for devising a secure probe based service discovery mechanism to reduce the complexity in providing the services to the network users. In this paper, we propose a Secure Service Discovery Based on Probe Packet Mechanism (SSDPPM for identifying the DoS attack in MANETs, which depicts a new approach for estimating the level of trust present in each and every routing path of a mobile ad hoc network by using probe packets. Probing based service discovery mechanisms mainly identifies a mobile node’s genuineness using a test packet called probe that travels the entire network for the sake of computing the degree of trust maintained between the mobile nodes and it’s attributed impact towards the network performance. The performance of SSDPPM is investigated through a wide range of network related parameters like packet delivery, throughput, Control overhead and total overhead using the version ns-2.26 network simulator. This mechanism SSDPPM, improves the performance of the network in an average by 23% and 19% in terms of packet delivery ratio and throughput than the existing service discovery mechanisms available in the literature.
-
Drug Discovery Gets a Boost from Data Science.
Amaro, Rommie E
2016-08-02
In this issue of Structure, Schiebel et al. (2016) describe a workflow-driven approach to high-throughput X-ray crystallographic fragment screening and refinement. In doing so, they extend the applicability of X-ray crystallography as a primary fragment-screening tool and show how data science techniques can favorably impact drug discovery efforts. Copyright © 2016 Elsevier Ltd. All rights reserved.
-
Met1-linked Ubiquitination in Immune Signalling
DEFF Research Database (Denmark)
Fiil, Berthe Katrine; Gyrd-Hansen, Mads
2014-01-01
Methionine 1-linked ubiquitin chains (Met1-Ub), or linear ubiquitin, has emerged as a central post-translational modification in innate immune signalling. Molecular machinery that assembles, senses and, more recently, disassembles Met1-Ub has been identified, and technical advances have enabled...... identification of physiological substrates for Met1-Ub in response to activation of innate immune receptors. These discoveries have significantly advanced our understanding of how non-degradative ubiquitin modifications control pro-inflammatory responses mediated by nuclear factor κB and mitogen...
-
Integration of Antibody Array Technology into Drug Discovery and Development.
Huang, Wei; Whittaker, Kelly; Zhang, Huihua; Wu, Jian; Zhu, Si-Wei; Huang, Ruo-Pan
Antibody arrays represent a high-throughput technique that enables the parallel detection of multiple proteins with minimal sample volume requirements. In recent years, antibody arrays have been widely used to identify new biomarkers for disease diagnosis or prognosis. Moreover, many academic research laboratories and commercial biotechnology companies are starting to apply antibody arrays in the field of drug discovery. In this review, some technical aspects of antibody array development and the various platforms currently available will be addressed; however, the main focus will be on the discussion of antibody array technologies and their applications in drug discovery. Aspects of the drug discovery process, including target identification, mechanisms of drug resistance, molecular mechanisms of drug action, drug side effects, and the application in clinical trials and in managing patient care, which have been investigated using antibody arrays in recent literature will be examined and the relevance of this technology in progressing this process will be discussed. Protein profiling with antibody array technology, in addition to other applications, has emerged as a successful, novel approach for drug discovery because of the well-known importance of proteins in cell events and disease development.
-
Data Mining and Knowledge Discovery via Logic-Based Methods
Triantaphyllou, Evangelos
2010-01-01
There are many approaches to data mining and knowledge discovery (DM&KD), including neural networks, closest neighbor methods, and various statistical methods. This monograph, however, focuses on the development and use of a novel approach, based on mathematical logic, that the author and his research associates have worked on over the last 20 years. The methods presented in the book deal with key DM&KD issues in an intuitive manner and in a natural sequence. Compared to other DM&KD methods, those based on mathematical logic offer a direct and often intuitive approach for extracting easily int
-
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.
-
Open-access public-private partnerships to enable drug discovery--new approaches.
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.
-
Directory of Open Access Journals (Sweden)
Duda Marlena
2012-11-01
Full Text Available Abstract Background Technological leaps in genome sequencing have resulted in a surge in discovery of human disease genes. These discoveries have led to increased clarity on the molecular pathology of disease and have also demonstrated considerable overlap in the genetic roots of human diseases. In light of this large genetic overlap, we tested whether cross-disease research approaches lead to faster, more impactful discoveries. Methods We leveraged several gene-disease association databases to calculate a Mutual Citation Score (MCS for 10,853 pairs of genetically related diseases to measure the frequency of cross-citation between research fields. To assess the importance of cooperative research, we computed an Individual Disease Cooperation Score (ICS and the average publication rate for each disease. Results For all disease pairs with one gene in common, we found that the degree of genetic overlap was a poor predictor of cooperation (r2=0.3198 and that the vast majority of disease pairs (89.56% never cited previous discoveries of the same gene in a different disease, irrespective of the level of genetic similarity between the diseases. A fraction (0.25% of the pairs demonstrated cross-citation in greater than 5% of their published genetic discoveries and 0.037% cross-referenced discoveries more than 10% of the time. We found strong positive correlations between ICS and publication rate (r2=0.7931, and an even stronger correlation between the publication rate and the number of cross-referenced diseases (r2=0.8585. These results suggested that cross-disease research may have the potential to yield novel discoveries at a faster pace than singular disease research. Conclusions Our findings suggest that the frequency of cross-disease study is low despite the high level of genetic similarity among many human diseases, and that collaborative methods may accelerate and increase the impact of new genetic discoveries. Until we have a better
-
PENGUATAN KARAKTER RASA INGIN TAHU DAN PEDULI SOSIAL MELALUI DISCOVERY LEARNING
Directory of Open Access Journals (Sweden)
Achmad Fauzi
2018-01-01
Full Text Available Efforts to strengthen the character become the basis in the implementation of the curriculum 2013. Application of the 2013 curriculum provides a paradigm shift, which in the end result of learning students not only master the knowledge but also master the attitude and skills. One of the two characters developed is curiosity and social care. To form the character, it needs an educational instrument such as a competent teacher, adequate learning resources, and the most important is the action of learning in the form of approach, model, method, or appropriate learning strategy. So the application of discovery learning model with scientific approach. Which model is effective and efficient in bring up the character of curiosity and social care. Keywords Curiosity, Social Care, Discovery Learning http://dx.doi.org/10.17977/um022v2i22017p079
-
The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses
Serkova, Natalie J.; Standiford, Theodore J.
2011-01-01
Metabolomics, a science of systems biology, is the global assessment of endogenous metabolites within a biologic system and represents a “snapshot” reading of gene function, enzyme activity, and the physiological landscape. Metabolite detection, either individual or grouped as a metabolomic profile, is usually performed in cells, tissues, or biofluids by either nuclear magnetic resonance spectroscopy or mass spectrometry followed by sophisticated multivariate data analysis. Because loss of metabolic homeostasis is common in critical illness, the metabolome could have many applications, including biomarker and drug target identification. Metabolomics could also significantly advance our understanding of the complex pathophysiology of acute illnesses, such as sepsis and acute lung injury/acute respiratory distress syndrome. Despite this potential, the clinical community is largely unfamiliar with the field of metabolomics, including the methodologies involved, technical challenges, and, most importantly, clinical uses. Although there is evidence of successful preclinical applications, the clinical usefulness and application of metabolomics in critical illness is just beginning to emerge, the advancement of which hinges on linking metabolite data to known and validated clinically relevant indices. In addition, other important aspects, such as patient selection, sample collection, and processing, as well as the needed multivariate data analysis, have to be taken into consideration before this innovative approach to biomarker discovery can become a reliable tool in the intensive care unit. The purpose of this review is to begin to familiarize clinicians with the field of metabolomics and its application for biomarker discovery in critical illnesses such as sepsis. PMID:21680948
-
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.
-
Linking biogeomorphic feedbacks from ecosystem engineer to landscape scale: a panarchy approach
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
-
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
-
Managing Your Team's Weakest Link.
Hills, Laura
2015-01-01
Do you have a poor-performing employee on your medical practice team? If so, you're not alone. Unfortunately, this is a problem that many medical practice managers face. This article describes the best strategies for managing your team's weakest link. It explores common yet very difficult circumstances that cause low employee performance and that test the patience, heart, and skills of a practice manager. It guides readers through a process of self-discovery to determine whether their negative biases or grudges may be causing employees to perform poorly. It suggests several possible other reasons for weak employee performance, including problems with the job, practice, leadership, communication, and fit between the employee and the job. This article also suggests the best strategy for communicating concerns about performance to the weakest-link employee. It offers guidance to practice managers about protecting their time and energy when handling a poor performer. It provides a simple formula for calculating the cost of a low-performing employee, 10 possible personal reasons for the employee's poor work performance, specific questions to ask to uncover the reasons for poor performance, and an eight-rule strategy for confronting poor performance effectively. Finally, this article offers practice managers a practical strategy for handling resistance from their weakest link, illustrated with a sample dialogue.
-
Melodic pattern discovery by structural analysis via wavelets and clustering techniques
DEFF Research Database (Denmark)
Velarde, Gissel; Meredith, David
We present an automatic method to support melodic pattern discovery by structural analysis of symbolic representations by means of wavelet analysis and clustering techniques. In previous work, we used the method to recognize the parent works of melodic segments, or to classify tunes into tune......-means to cluster melodic segments into groups of measured similarity and obtain a raking of the most prototypical melodic segments or patterns and their occurrences. We test the method on the JKU Patterns Development Database and evaluate it based on the ground truth defined by the MIREX 2013 Discovery of Repeated...... Themes & Sections task. We compare the results of our method to the output of geometric approaches. Finally, we discuss about the relevance of our wavelet-based analysis in relation to structure, pattern discovery, similarity and variation, and comment about the considerations of the method when used...
-
Fragment-based drug discovery and protein–protein interactions
Directory of Open Access Journals (Sweden)
Turnbull AP
2014-09-01
Full Text Available Andrew P Turnbull,1 Susan M Boyd,2 Björn Walse31CRT Discovery Laboratories, Department of Biological Sciences, Birkbeck, University of London, London, UK; 2IOTA Pharmaceuticals Ltd, Cambridge, UK; 3SARomics Biostructures AB, Lund, SwedenAbstract: Protein–protein interactions (PPIs are involved in many biological processes, with an estimated 400,000 PPIs within the human proteome. There is significant interest in exploiting the relatively unexplored potential of these interactions in drug discovery, driven by the need to find new therapeutic targets. Compared with classical drug discovery against targets with well-defined binding sites, developing small-molecule inhibitors against PPIs where the contact surfaces are frequently more extensive and comparatively flat, with most of the binding energy localized in “hot spots”, has proven far more challenging. However, despite the difficulties associated with targeting PPIs, important progress has been made in recent years with fragment-based drug discovery playing a pivotal role in improving their tractability. Computational and empirical approaches can be used to identify hot-spot regions and assess the druggability and ligandability of new targets, whilst fragment screening campaigns can detect low-affinity fragments that either directly or indirectly perturb the PPI. Once fragment hits have been identified and confirmed using biochemical and biophysical approaches, three-dimensional structural data derived from nuclear magnetic resonance or X-ray crystallography can be used to drive medicinal chemistry efforts towards the development of more potent inhibitors. A small-scale comparison presented in this review of “standard” fragments with those targeting PPIs has revealed that the latter tend to be larger, be more lipophilic, and contain more polar (acid/base functionality, whereas three-dimensional descriptor data indicate that there is little difference in their three
-
A Tale of Two Discoveries: Comparing the Usability of Summon and EBSCO Discovery Service
Foster, Anita K.; MacDonald, Jean B.
2013-01-01
Web-scale discovery systems are gaining momentum among academic libraries as libraries seek a means to provide their users with a one-stop searching experience. Illinois State University's Milner Library found itself in the unique position of having access to two distinct discovery products, EBSCO Discovery Service and Serials Solutions' Summon.…
-
Gomez, Gabriel; Adams, Leslie G.; Rice-Ficht, Allison; Ficht, Thomas A.
2013-01-01
Vaccination is the most important approach to counteract infectious diseases. Thus, the development of new and improved vaccines for existing, emerging, and re-emerging diseases is an area of great interest to the scientific community and general public. Traditional approaches to subunit antigen discovery and vaccine development lack consideration for the critical aspects of public safety and activation of relevant protective host immunity. The availability of genomic sequences for pathogenic Brucella spp. and their hosts have led to development of systems-wide analytical tools that have provided a better understanding of host and pathogen physiology while also beginning to unravel the intricacies at the host-pathogen interface. Advances in pathogen biology, host immunology, and host-agent interactions have the potential to serve as a platform for the design and implementation of better-targeted antigen discovery approaches. With emphasis on Brucella spp., we probe the biological aspects of host and pathogen that merit consideration in the targeted design of subunit antigen discovery and vaccine development. PMID:23720712
-
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
-
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.
-
Public-Private Partnerships in Lead Discovery: Overview and Case Studies.
Gottwald, Matthias; Becker, Andreas; Bahr, Inke; Mueller-Fahrnow, Anke
2016-09-01
The pharmaceutical industry is faced with significant challenges in its efforts to discover new drugs that address unmet medical needs. Safety concerns and lack of efficacy are the two main technical reasons for attrition. Improved early research tools including predictive in silico, in vitro, and in vivo models, as well as a deeper understanding of the disease biology, therefore have the potential to improve success rates. The combination of internal activities with external collaborations in line with the interests and needs of all partners is a successful approach to foster innovation and to meet the challenges. Collaboration can take place in different ways, depending on the requirements of the participants. In this review, the value of public-private partnership approaches will be discussed, using examples from the Innovative Medicines Initiative (IMI). These examples describe consortia approaches to develop tools and processes for improving target identification and validation, as well as lead identification and optimization. The project "Kinetics for Drug Discovery" (K4DD), focusing on the adoption of drug-target binding kinetics analysis in the drug discovery decision-making process, is described in more detail. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
-
2010-07-01
... 29 Labor 9 2010-07-01 2010-07-01 false Discovery. 2200.208 Section 2200.208 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION RULES OF PROCEDURE Simplified Proceedings § 2200.208 Discovery. Discovery, including requests for admissions, will only be...
-
2010-10-01
... 47 Telecommunication 3 2010-10-01 2010-10-01 false Discovery. 65.105 Section 65.105... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Procedures § 65.105 Discovery. (a) Participants... evidence. (c) Discovery requests pursuant to § 65.105(b), including written interrogatories, shall be filed...
-
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Discovery. 209.313 Section 209.313 Transportation... TRANSPORTATION RAILROAD SAFETY ENFORCEMENT PROCEDURES Disqualification Procedures § 209.313 Discovery. (a... parties. Discovery is designed to enable a party to obtain relevant information needed for preparation of...
-
Strategies for Discovery of Small Molecule Radiation Protectors and Radiation Mitigators
Directory of Open Access Journals (Sweden)
Joel S Greenberger
2012-01-01
Full Text Available Mitochondrial targeted radiation damage protectors (delivered prior to irradiation and mitigators (delivered after irradiation, but before the appearance of symptoms associated with radiation syndrome have been a recent focus in drug discovery for 1 normal tissue radiation protection during fractionated radiotherapy, and 2 radiation terrorism counter measures. Several categories of such molecules have been discovered: nitroxide-linked hybrid molecules, including GS-nitroxide, GS-nitric oxide synthase inhibitors, p53/mdm2/mdm4 inhibitors, and pharmaceutical agents including inhibitors of the phosphoinositide-3-kinase pathway and the anti-seizure medicine, carbamazepine. Evaluation of potential new irradiation dose modifying molecules to protect normal tissue includes: clonagenic radiation survival curves; assays for apoptosis and DNA repair, and irradiation-induced depletion of antioxidant stores. Studies of organ specific radioprotection and in total body irradiation-induced hematopoietic syndrome in the mouse model for protection/mitigation facilitate rational means by which to move candidate small molecule drugs along the drug discovery pipeline into clinical development.
-
Strategies for Discovery of Small Molecule Radiation Protectors and Radiation Mitigators
Energy Technology Data Exchange (ETDEWEB)
Greenberger, Joel S.; Clump, David [Radiation Oncology Department, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Kagan, Valerian [Environmental and Occupational Health Department, University of Pittsburgh, Pittsburgh, PA (United States); Bayir, Hülya [Critical Care Medicine Department, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Lazo, John S. [Pharmacology Department, University of Virginia, Charlottesville, VA (United States); Wipf, Peter [Department of Chemistry, Accelerated Chemical Discovery Center, University of Pittsburgh, Pittsburgh, PA (United States); Li, Song; Gao, Xiang [Pharmaceutical Science Department, University of Pittsburgh, Pittsburgh, PA (United States); Epperly, Michael W., E-mail: greenbergerjs@upmc.edu [Radiation Oncology Department, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States)
2012-01-13
Mitochondrial targeted radiation damage protectors (delivered prior to irradiation) and mitigators (delivered after irradiation, but before the appearance of symptoms associated with radiation syndrome) have been a recent focus in drug discovery for (1) normal tissue radiation protection during fractionated radiotherapy, and (2) radiation terrorism counter measures. Several categories of such molecules have been discovered: nitroxide-linked hybrid molecules, including GS-nitroxide, GS-nitric oxide synthase inhibitors, p53/mdm2/mdm4 inhibitors, and pharmaceutical agents including inhibitors of the phosphoinositide-3-kinase pathway and the anti-seizure medicine, carbamazepine. Evaluation of potential new radiation dose modifying molecules to protect normal tissue includes: clonogenic radiation survival curves, assays for apoptosis and DNA repair, and irradiation-induced depletion of antioxidant stores. Studies of organ specific radioprotection and in total body irradiation-induced hematopoietic syndrome in the mouse model for protection/mitigation facilitate rational means by which to move candidate small molecule drugs along the drug discovery pipeline into clinical development.
-
Quantifying the Ease of Scientific Discovery.
Arbesman, Samuel
2011-02-01
It has long been known that scientific output proceeds on an exponential increase, or more properly, a logistic growth curve. The interplay between effort and discovery is clear, and the nature of the functional form has been thought to be due to many changes in the scientific process over time. Here I show a quantitative method for examining the ease of scientific progress, another necessary component in understanding scientific discovery. Using examples from three different scientific disciplines - mammalian species, chemical elements, and minor planets - I find the ease of discovery to conform to an exponential decay. In addition, I show how the pace of scientific discovery can be best understood as the outcome of both scientific output and ease of discovery. A quantitative study of the ease of scientific discovery in the aggregate, such as done here, has the potential to provide a great deal of insight into both the nature of future discoveries and the technical processes behind discoveries in science.
-
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.
-
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.
-
2010-01-01
... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Discovery. 280.210 Section 280.210... STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE ACCREDITATION AND ASSESSMENT PROGRAMS FASTENER QUALITY Enforcement § 280.210 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery...
-
Computational methods for a three-dimensional model of the petroleum-discovery process
Schuenemeyer, J.H.; Bawiec, W.J.; Drew, L.J.
1980-01-01
A discovery-process model devised by Drew, Schuenemeyer, and Root can be used to predict the amount of petroleum to be discovered in a basin from some future level of exploratory effort: the predictions are based on historical drilling and discovery data. Because marginal costs of discovery and production are a function of field size, the model can be used to make estimates of future discoveries within deposit size classes. The modeling approach is a geometric one in which the area searched is a function of the size and shape of the targets being sought. A high correlation is assumed between the surface-projection area of the fields and the volume of petroleum. To predict how much oil remains to be found, the area searched must be computed, and the basin size and discovery efficiency must be estimated. The basin is assumed to be explored randomly rather than by pattern drilling. The model may be used to compute independent estimates of future oil at different depth intervals for a play involving multiple producing horizons. We have written FORTRAN computer programs that are used with Drew, Schuenemeyer, and Root's model to merge the discovery and drilling information and perform the necessary computations to estimate undiscovered petroleum. These program may be modified easily for the estimation of remaining quantities of commodities other than petroleum. ?? 1980.
-
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.
-
Concept Formation in Scientific Knowledge Discovery from a Constructivist View
Peng, Wei; Gero, John S.
The central goal of scientific knowledge discovery is to learn cause-effect relationships among natural phenomena presented as variables and the consequences their interactions. Scientific knowledge is normally expressed as scientific taxonomies and qualitative and quantitative laws [1]. This type of knowledge represents intrinsic regularities of the observed phenomena that can be used to explain and predict behaviors of the phenomena. It is a generalization that is abstracted and externalized from a set of contexts and applicable to a broader scope. Scientific knowledge is a type of third-person knowledge, i.e., knowledge that independent of a specific enquirer. Artificial intelligence approaches, particularly data mining algorithms that are used to identify meaningful patterns from large data sets, are approaches that aim to facilitate the knowledge discovery process [2]. A broad spectrum of algorithms has been developed in addressing classification, associative learning, and clustering problems. However, their linkages to people who use them have not been adequately explored. Issues in relation to supporting the interpretation of the patterns, the application of prior knowledge to the data mining process and addressing user interactions remain challenges for building knowledge discovery tools [3]. As a consequence, scientists rely on their experience to formulate problems, evaluate hypotheses, reason about untraceable factors and derive new problems. This type of knowledge which they have developed during their career is called "first-person" knowledge. The formation of scientific knowledge (third-person knowledge) is highly influenced by the enquirer's first-person knowledge construct, which is a result of his or her interactions with the environment. There have been attempts to craft automatic knowledge discovery tools but these systems are limited in their capabilities to handle the dynamics of personal experience. There are now trends in developing
-
Proteomic biomarker discovery in 1000 human plasma samples with mass spectrometry
DEFF Research Database (Denmark)
Cominetti, Ornella; Núñez Galindo, Antonio; Corthésy, John
2016-01-01
automated proteomic biomarker discovery workflow. Herein, we have applied this approach to analyze 1000 plasma samples from the multicentered human dietary intervention study "DiOGenes". Study design, sample randomization, tracking, and logistics were the foundations of our large-scale study. We checked...
-
2010-01-01
... 10 Energy 4 2010-01-01 2010-01-01 false Discovery. 1013.21 Section 1013.21 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) PROGRAM FRAUD CIVIL REMEDIES AND PROCEDURES § 1013.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and...
-
2010-07-01
... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Discovery. 2.120 Section 2... COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Procedure in Inter Partes Proceedings § 2.120 Discovery. (a... to disclosure and discovery shall apply in opposition, cancellation, interference and concurrent use...
-
2010-10-01
... 46 Shipping 9 2010-10-01 2010-10-01 false Discovery. 550.502 Section 550.502 Shipping FEDERAL... Proceedings § 550.502 Discovery. The Commission may authorize a party to a proceeding to use depositions, written interrogatories, and discovery procedures that, to the extent practicable, are in conformity with...
-
2010-01-01
... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 785.8 Section 785.8... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS ENFORCEMENT § 785.8 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter, not...
-
2010-04-01
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 35.21 Section 35.21 Foreign Relations DEPARTMENT OF STATE CLAIMS AND STOLEN PROPERTY PROGRAM FRAUD CIVIL REMEDIES § 35.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...
-
2010-10-01
... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 96.65 Section 96.65 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Hearing Procedure § 96.65 Discovery. The use of interrogatories, depositions, and other forms of discovery shall not be allowed. ...
-
2010-10-01
... 49 Transportation 1 2010-10-01 2010-10-01 false Discovery. 31.21 Section 31.21 Transportation Office of the Secretary of Transportation PROGRAM FRAUD CIVIL REMEDIES § 31.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and...
-
43 CFR 4.1130 - Discovery methods.
2010-10-01
... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discovery methods. 4.1130 Section 4.1130... Special Rules Applicable to Surface Coal Mining Hearings and Appeals Discovery § 4.1130 Discovery methods. Parties may obtain discovery by one or more of the following methods— (a) Depositions upon oral...
-
Current Landscape of Antiviral Drug Discovery [version 1; referees: 2 approved
Directory of Open Access Journals (Sweden)
Wade Blair
2016-02-01
Full Text Available Continued discovery and development of new antiviral medications are paramount for global human health, particularly as new pathogens emerge and old ones evolve to evade current therapeutic agents. Great success has been achieved in developing effective therapies to suppress human immunodeficiency virus (HIV and hepatitis B virus (HBV; however, the therapies are not curative and therefore current efforts in HIV and HBV drug discovery are directed toward longer-acting therapies and/or developing new mechanisms of action that could potentially lead to cure, or eradication, of the virus. Recently, exciting early clinical data have been reported for novel antivirals targeting respiratory syncytial virus (RSV and influenza (flu. Preclinical data suggest that these new approaches may be effective in treating high-risk patients afflicted with serious RSV or flu infections. In this review, we highlight new directions in antiviral approaches for HIV, HBV, and acute respiratory virus infections.
-
2010-01-01
... 6 Domestic Security 1 2010-01-01 2010-01-01 false Discovery. 13.21 Section 13.21 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) In general. (1) The following types of discovery are authorized: (i) Requests for production of...
-
2010-10-01
... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 99.23 Section 99.23 Public Welfare... DEVELOPMENT FUND Hearing Procedures § 99.23 Discovery. The Department, the Lead Agency, and any individuals or groups recognized as parties shall have the right to conduct discovery (including depositions) against...
-
2010-04-01
... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Discovery. 355.21 Section 355.21 Employees... UNDER THE PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 355.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...
-
2010-01-01
... 10 Energy 1 2010-01-01 2010-01-01 false Discovery. 2.1018 Section 2.1018 Energy NUCLEAR REGULATORY... Geologic Repository § 2.1018 Discovery. (a)(1) Parties, potential parties, and interested governmental participants in the high-level waste licensing proceeding may obtain discovery by one or more of the following...
-
2010-07-01
... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Discovery. 71.21 Section 71.21 Judicial... REMEDIES ACT OF 1986 Implementation for Actions Initiated by the Department of Justice § 71.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...
-
2010-01-01
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Discovery. 134.310 Section 134.310 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION RULES OF PROCEDURE GOVERNING CASES BEFORE THE... Designations § 134.310 Discovery. Discovery will not be permitted in appeals from size determinations or NAICS...
-
2010-07-01
... 34 Education 1 2010-07-01 2010-07-01 false Discovery. 33.21 Section 33.21 Education Office of the Secretary, Department of Education PROGRAM FRAUD CIVIL REMEDIES ACT § 33.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying...
-
2010-07-01
... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Discovery. 18.7 Section 18.7 Judicial Administration DEPARTMENT OF JUSTICE OFFICE OF JUSTICE PROGRAMS HEARING AND APPEAL PROCEDURES § 18.7 Discovery.... Such order may be entered upon a showing that the deposition is necessary for discovery purposes, and...
-
2010-01-01
... 7 Agriculture 1 2010-01-01 2010-01-01 false Discovery. 1.322 Section 1.322 Agriculture Office of... Under the Program Fraud Civil Remedies Act of 1986 § 1.322 Discovery. (a) The following types of discovery are authorized: (1) Requests for production, inspection and photocopying of documents; (2...
-
2010-10-01
... 45 Public Welfare 4 2010-10-01 2010-10-01 false Discovery. 1386.103 Section 1386.103 Public... Hearing Procedures § 1386.103 Discovery. The Department and any party named in the Notice issued pursuant to § 1386.90 has the right to conduct discovery (including depositions) against opposing parties as...
-
2010-10-01
... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 79.21 Section 79.21 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...
-
2010-01-01
... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Discovery. 308.520 Section 308.520 Banks and... PROCEDURE Program Fraud Civil Remedies and Procedures § 308.520 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...
-
2010-10-01
... 47 Telecommunication 1 2010-10-01 2010-10-01 false Discovery. 1.729 Section 1.729..., and Reports Involving Common Carriers Formal Complaints § 1.729 Discovery. (a) Subject to paragraph (i... seek discovery of any non-privileged matter that is relevant to the material facts in dispute in the...
-
2010-01-01
... 7 Agriculture 4 2010-01-01 2010-01-01 false Discovery. 283.12 Section 283.12 Agriculture... of $50,000 or More § 283.12 Discovery. (a) Dispositions—(1) Motion for taking deposition. Only upon a... exist if the information sought appears reasonably calculated to lead to the discovery of admissible...
-
NEW COMPLETENESS METHODS FOR ESTIMATING EXOPLANET DISCOVERIES BY DIRECT DETECTION
International Nuclear Information System (INIS)
Brown, Robert A.; Soummer, Remi
2010-01-01
We report on new methods for evaluating realistic observing programs that search stars for planets by direct imaging, where observations are selected from an optimized star list and stars can be observed multiple times. We show how these methods bring critical insight into the design of the mission and its instruments. These methods provide an estimate of the outcome of the observing program: the probability distribution of discoveries (detection and/or characterization) and an estimate of the occurrence rate of planets (η). We show that these parameters can be accurately estimated from a single mission simulation, without the need for a complete Monte Carlo mission simulation, and we prove the accuracy of this new approach. Our methods provide tools to define a mission for a particular science goal; for example, a mission can be defined by the expected number of discoveries and its confidence level. We detail how an optimized star list can be built and how successive observations can be selected. Our approach also provides other critical mission attributes, such as the number of stars expected to be searched and the probability of zero discoveries. Because these attributes depend strongly on the mission scale (telescope diameter, observing capabilities and constraints, mission lifetime, etc.), our methods are directly applicable to the design of such future missions and provide guidance to the mission and instrument design based on scientific performance. We illustrate our new methods with practical calculations and exploratory design reference missions for the James Webb Space Telescope (JWST) operating with a distant starshade to reduce scattered and diffracted starlight on the focal plane. We estimate that five habitable Earth-mass planets would be discovered and characterized with spectroscopy, with a probability of zero discoveries of 0.004, assuming a small fraction of JWST observing time (7%), η = 0.3, and 70 observing visits, limited by starshade fuel.
-
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.
-
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.
-
IMG-ABC: An Atlas of Biosynthetic Gene Clusters to Fuel the Discovery of Novel Secondary Metabolites
Energy Technology Data Exchange (ETDEWEB)
Chen, I-Min; Chu, Ken; Ratner, Anna; Palaniappan, Krishna; Huang, Jinghua; Reddy, T. B.K.; Cimermancic, Peter; Fischbach, Michael; Ivanova, Natalia; Markowitz, Victor; Kyrpides, Nikos; Pati, Amrita
2014-10-28
In the discovery of secondary metabolites (SMs), large-scale analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of relevant computational resources. We present IMG-ABC (https://img.jgi.doe.gov/abc/) -- An Atlas of Biosynthetic gene Clusters within the Integrated Microbial Genomes (IMG) system1. IMG-ABC is a rich repository of both validated and predicted biosynthetic clusters (BCs) in cultured isolates, single-cells and metagenomes linked with the SM chemicals they produce and enhanced with focused analysis tools within IMG. The underlying scalable framework enables traversal of phylogenetic dark matter and chemical structure space -- serving as a doorway to a new era in the discovery of novel molecules.
-
Improving functional modules discovery by enriching interaction networks with gene profiles
Salem, Saeed
2013-05-01
Recent advances in proteomic and transcriptomic technologies resulted in the accumulation of vast amount of high-throughput data that span multiple biological processes and characteristics in different organisms. Much of the data come in the form of interaction networks and mRNA expression arrays. An important task in systems biology is functional modules discovery where the goal is to uncover well-connected sub-networks (modules). These discovered modules help to unravel the underlying mechanisms of the observed biological processes. While most of the existing module discovery methods use only the interaction data, in this work we propose, CLARM, which discovers biological modules by incorporating gene profiles data with protein-protein interaction networks. We demonstrate the effectiveness of CLARM on Yeast and Human interaction datasets, and gene expression and molecular function profiles. Experiments on these real datasets show that the CLARM approach is competitive to well established functional module discovery methods.
-
2010-10-01
... 42 Public Health 5 2010-10-01 2010-10-01 false Discovery. 1005.7 Section 1005.7 Public Health... OF EXCLUSIONS, CIVIL MONEY PENALTIES AND ASSESSMENTS § 1005.7 Discovery. (a) A party may make a... and any forms of discovery, other than those permitted under paragraph (a) of this section, are not...
-
2010-07-01
... 29 Labor 4 2010-07-01 2010-07-01 false Discovery. 1603.210 Section 1603.210 Labor Regulations... GOVERNMENT EMPLOYEE RIGHTS ACT OF 1991 Hearings § 1603.210 Discovery. (a) Unless otherwise ordered by the administrative law judge, discovery may begin as soon as the complaint has been transmitted to the administrative...
-
2010-10-01
... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 150.435 Section 150.435 Public Welfare... AND INDIVIDUAL INSURANCE MARKETS Administrative Hearings § 150.435 Discovery. (a) The parties must identify any need for discovery from the opposing party as soon as possible, but no later than the time for...
-
2010-07-01
... 34 Education 1 2010-07-01 2010-07-01 false Discovery. 81.16 Section 81.16 Education Office of the... Discovery. (a) The parties to a case are encouraged to exchange relevant documents and information voluntarily. (b) The ALJ, at a party's request, may order compulsory discovery described in paragraph (c) of...
-
2010-07-01
... 29 Labor 5 2010-07-01 2010-07-01 false Discovery. 1905.25 Section 1905.25 Labor Regulations... OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 Hearings § 1905.25 Discovery. (a) Depositions. (1) For reasons of... discovery. Whenever appropriate to a just disposition of any issue in a hearing, the presiding hearing...
-
2010-01-01
... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Discovery. 1780.26 Section 1780.26 Banks and... OF PRACTICE AND PROCEDURE RULES OF PRACTICE AND PROCEDURE Prehearing Proceedings § 1780.26 Discovery. (a) Limits on discovery. Subject to the limitations set out in paragraphs (b), (d), and (e) of this...
-
2010-10-01
... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 160.516 Section 160.516 Public Welfare... ADMINISTRATIVE REQUIREMENTS Procedures for Hearings § 160.516 Discovery. (a) A party may make a request to... forms of discovery, other than those permitted under paragraph (a) of this section, are not authorized...
-
2010-10-01
... 42 Public Health 4 2010-10-01 2010-10-01 false Discovery. 430.86 Section 430.86 Public Health... Plans and Practice to Federal Requirements § 430.86 Discovery. CMS and any party named in the notice issued under § 430.70 has the right to conduct discovery (including depositions) against opposing parties...
-
Wyss, Daniel F; Wang, Yu-Sen; Eaton, Hugh L; Strickland, Corey; Voigt, Johannes H; Zhu, Zhaoning; Stamford, Andrew W
2012-01-01
Fragment-based drug discovery (FBDD) has become increasingly popular over the last decade. We review here how we have used highly structure-driven fragment-based approaches to complement more traditional lead discovery to tackle high priority targets and those struggling for leads. Combining biomolecular nuclear magnetic resonance (NMR), X-ray crystallography, and molecular modeling with structure-assisted chemistry and innovative biology as an integrated approach for FBDD can solve very difficult problems, as illustrated in this chapter. Here, a successful FBDD campaign is described that has allowed the development of a clinical candidate for BACE-1, a challenging CNS drug target. Crucial to this achievement were the initial identification of a ligand-efficient isothiourea fragment through target-based NMR screening and the determination of its X-ray crystal structure in complex with BACE-1, which revealed an extensive H-bond network with the two active site aspartate residues. This detailed 3D structural information then enabled the design and validation of novel, chemically stable and accessible heterocyclic acylguanidines as aspartic acid protease inhibitor cores. Structure-assisted fragment hit-to-lead optimization yielded iminoheterocyclic BACE-1 inhibitors that possess desirable molecular properties as potential therapeutic agents to test the amyloid hypothesis of Alzheimer's disease in a clinical setting.
-
Directory of Open Access Journals (Sweden)
Elyes Ben Hamida
2008-04-01
Full Text Available In this paper, we study the impact of collisions and interferences on a neighbor discovery process in the context of multi-hop wireless networks. We consider three models in which interferences and collisions are handled in very different ways. From an ideal channel where simultaneous transmissions do not interfere, we derive an alternate channel where simultaneous transmissions are considered two-by-two under the form of collisions, to finally reach a more realistic channel where simultaneous transmissions are handled under the form of shot-noise interferences. In these models, we analytically compute the link probability success between two neighbors as well as the expected number of nodes that correctly receive a Hello packet. Using this analysis, we show that if the neighbor discovery process is asymptotically equivalent in the three models, it offers very different behaviors locally in time. In particular, the scalability of the process is not the same depending on the way interferences are handled. Finally, we apply our results to the dimensioning of a Hello protocol parameters. We propose a method to adapt the protocol parameters to meet application constraints on the neighbor discovery process and to minimize the protocol energy consumption.
-
Network-Assisted Device-to-Device (D2D) Direct Proximity Discovery with Underlay Communication
DEFF Research Database (Denmark)
Pratas, Nuno; Popovski, Petar
2015-01-01
) direct communication between proximate devices. While (ii) is treated extensively in the recent literature, (i) has received relatively little attention. In this paper we analyze a network-assisted underlay proximity discovery protocol, where a cellular device can take the role of: announcer (which......Device-to-Device communications are expected to play an important role in current and future cellular generations, by increasing the spatial reuse of spectrum resources and enabling lower latency communication links. This paradigm has two fundamental building blocks: (i) proximity discovery and (ii......, we consider the case where the announcers underlay their messages in the downlink transmissions that are directed towards the monitoring devices. We propose a power control scheme applied to the downlink transmission, which copes with the underlay transmission via additional power expenditure, while...
-
Directory of Open Access Journals (Sweden)
Debasish Paul
2013-01-01
Full Text Available Accurate diagnosis and proper monitoring of cancer patients remain a key obstacle for successful cancer treatment and prevention. Therein comes the need for biomarker discovery, which is crucial to the current oncological and other clinical practices having the potential to impact the diagnosis and prognosis. In fact, most of the biomarkers have been discovered utilizing the proteomics-based approaches. Although high-throughput mass spectrometry-based proteomic approaches like SILAC, 2D-DIGE, and iTRAQ are filling up the pitfalls of the conventional techniques, still serum proteomics importunately poses hurdle in overcoming a wide range of protein concentrations, and also the availability of patient tissue samples is a limitation for the biomarker discovery. Thus, researchers have looked for alternatives, and profiling of candidate biomarkers through tissue culture of tumor cell lines comes up as a promising option. It is a rich source of tumor cell-derived proteins, thereby, representing a wide array of potential biomarkers. Interestingly, most of the clinical biomarkers in use today (CA 125, CA 15.3, CA 19.9, and PSA were discovered through tissue culture-based system and tissue extracts. This paper tries to emphasize the tissue culture-based discovery of candidate biomarkers through various mass spectrometry-based proteomic approaches.
-
Paul, Debasish; Kumar, Avinash; Gajbhiye, Akshada; Santra, Manas K.; Srikanth, Rapole
2013-01-01
Accurate diagnosis and proper monitoring of cancer patients remain a key obstacle for successful cancer treatment and prevention. Therein comes the need for biomarker discovery, which is crucial to the current oncological and other clinical practices having the potential to impact the diagnosis and prognosis. In fact, most of the biomarkers have been discovered utilizing the proteomics-based approaches. Although high-throughput mass spectrometry-based proteomic approaches like SILAC, 2D-DIGE, and iTRAQ are filling up the pitfalls of the conventional techniques, still serum proteomics importunately poses hurdle in overcoming a wide range of protein concentrations, and also the availability of patient tissue samples is a limitation for the biomarker discovery. Thus, researchers have looked for alternatives, and profiling of candidate biomarkers through tissue culture of tumor cell lines comes up as a promising option. It is a rich source of tumor cell-derived proteins, thereby, representing a wide array of potential biomarkers. Interestingly, most of the clinical biomarkers in use today (CA 125, CA 15.3, CA 19.9, and PSA) were discovered through tissue culture-based system and tissue extracts. This paper tries to emphasize the tissue culture-based discovery of candidate biomarkers through various mass spectrometry-based proteomic approaches. PMID:23586059
-
Genome engineering for microbial natural product discovery.
Choi, Si-Sun; Katsuyama, Yohei; Bai, Linquan; Deng, Zixin; Ohnishi, Yasuo; Kim, Eung-Soo
2018-03-03
The discovery and development of microbial natural products (MNPs) have played pivotal roles in the fields of human medicine and its related biotechnology sectors over the past several decades. The post-genomic era has witnessed the development of microbial genome mining approaches to isolate previously unsuspected MNP biosynthetic gene clusters (BGCs) hidden in the genome, followed by various BGC awakening techniques to visualize compound production. Additional microbial genome engineering techniques have allowed higher MNP production titers, which could complement a traditional culture-based MNP chasing approach. Here, we describe recent developments in the MNP research paradigm, including microbial genome mining, NP BGC activation, and NP overproducing cell factory design. Copyright © 2018 Elsevier Ltd. All rights reserved.
-
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...
-
Pemodelan Matematika Premi Tunggal Bersih Asuransi Unit Link Syariah
Directory of Open Access Journals (Sweden)
Nanang Supriadi
2017-12-01
Full Text Available The exact risk factor can be managed by transferring the risk to the other party (in this case the insurance company. In this paper will be discussed more life insurance, as the development now there are types of insurance combined with investment, which is popular with the term Unit Link insurance. Unit link Syariah began to be launched as one of the fulfilment of the high needs of the community, the privilege of the product Unit of Islamic links is actually located in the elements of the laws in accordance with Islamic Syariah. The issues that will be discussed are how to get a single premium model of life insurance unit link Syariah with life insurance and investment fund allocation invested in investment product with a big interest rate of risk (financial approach and investment product with the value of return maximum (actuarial approach. The resulting model is then implemented in case of examples by comparing the two approaches to see the shortcomings and advantages of Unit link lifetime life insurance when compared to life insurance. The result obtained from this research is the benefit obtained from Unit-linked sharia insurance on average will be greater if compared with life insurance for life, maximum benefit will be obtained Insurance Unit Link of sharia using actuarial approach compared to financial, but benefit with a relative financial approach more stable than actuarial approaches that tend to fluctuate.
-
2010-10-01
... 42 Public Health 2 2010-10-01 2010-10-01 false Discovery. 405.1037 Section 405.1037 Public Health... Appeals Under Original Medicare (Part A and Part B) Alj Hearings § 405.1037 Discovery. (a) General rules. (1) Discovery is permissible only when CMS or its contractor elects to participate in an ALJ hearing...
-
2010-04-01
... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Discovery. 498.207 Section 498.207 Employees... § 498.207 Discovery. (a) For the purpose of inspection and copying, a party may make a request to...) Any form of discovery other than that permitted under paragraph (a) of this section, such as requests...
-
2010-10-01
... 42 Public Health 1 2010-10-01 2010-10-01 false Discovery. 93.512 Section 93.512 Public Health... Process § 93.512 Discovery. (a) Request to provide documents. A party may only request another party to...) Responses to a discovery request. Within 30 days of receiving a request for the production of documents, a...
-
2010-10-01
... 42 Public Health 1 2010-10-01 2010-10-01 false Discovery. 3.516 Section 3.516 Public Health PUBLIC... AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.516 Discovery. (a) A party may make a request... and any forms of discovery, other than those permitted under paragraph (a) of this section, are not...
-
2010-07-01
... 29 Labor 1 2010-07-01 2010-07-01 true Discovery. 22.21 Section 22.21 Labor Office of the Secretary of Labor PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 22.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...
-
Impact of the discovery of radioactivity on the evolution of technologies
International Nuclear Information System (INIS)
Kalyazin, E.P.
1996-01-01
Radioactivity discovery and practical application of nuclear power gave impetus to the development of radiation technologies primarily as a by-side trend of radiation materials technology. Paper studies the place occupied by radiation technologies within the system of the modern-day production processes starting from exploration, mining, enrichment and treatment of minerals and ending with production of materials, articles and special devices. Paper shows the promising character of radiation technologies to be used for the purposes linked with the environmental protection, with power and resource savings. 41 refs., 2 figs., 1 tab
-
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.
-
Medical imaging was boosted by the discovery of artificial radioactivity
International Nuclear Information System (INIS)
Demarthon, F.; Dupuy-Maury, F.; Donnars, O.
2002-01-01
This article draws the history of medical imaging since the discovery of artificial radioactivity in 1934. The author reviews the PET (positron emission tomography) and MRI (magnetic resonance imaging) technologies and presents the recent progress in neuro-sciences that have been made possible by using these 2 technologies. Brain imaging has allowed to show: - the impact of emotions on logical mental processes and on mental performances, - the management of memory in the brain of talented quick reckoners, - the degeneration of neurons, and - the link between autism and the presence of structural and functional anomalies in the brain. (A.C.)
-
KOJAK: Scalable Semantic Link Discovery Via Integrated Knowledge-Based and Statistical Reasoning
2006-11-01
group is pruned using a threshold to produce the final output. Table 1 Y2 Y2.5 Y3 Entities 10,000 10,000 100,000 Links 100,000 100,000 1,000,000 F...strongly connected they are to the seed members. Fourth, the ranked extended group is pruned using a threshold to produce the final output. The...people may eat at the same restaurant, drink coffee at the same cafe and take the same train to work every day without any strongly meaningful 34
-
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
-
Computational medicinal chemistry in fragment-based drug discovery: what, how and when.
Rabal, Obdulia; Urbano-Cuadrado, Manuel; Oyarzabal, Julen
2011-01-01
The use of fragment-based drug discovery (FBDD) has increased in the last decade due to the encouraging results obtained to date. In this scenario, computational approaches, together with experimental information, play an important role to guide and speed up the process. By default, FBDD is generally considered as a constructive approach. However, such additive behavior is not always present, therefore, simple fragment maturation will not always deliver the expected results. In this review, computational approaches utilized in FBDD are reported together with real case studies, where applicability domains are exemplified, in order to analyze them, and then, maximize their performance and reliability. Thus, a proper use of these computational tools can minimize misleading conclusions, keeping the credit on FBDD strategy, as well as achieve higher impact in the drug-discovery process. FBDD goes one step beyond a simple constructive approach. A broad set of computational tools: docking, R group quantitative structure-activity relationship, fragmentation tools, fragments management tools, patents analysis and fragment-hopping, for example, can be utilized in FBDD, providing a clear positive impact if they are utilized in the proper scenario - what, how and when. An initial assessment of additive/non-additive behavior is a critical point to define the most convenient approach for fragments elaboration.
-
2010-01-01
... 10 Energy 3 2010-01-01 2010-01-01 false Discovery. 205.198 Section 205.198 Energy DEPARTMENT OF... of Proposed Disallowance, and Order of Disallowance § 205.198 Discovery. (a) If a person intends to file a Motion for Discovery, he must file it at the same time that he files his Statement of Objections...
-
2010-01-01
... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Discovery. 908.46 Section 908.46 Banks and... PRACTICE AND PROCEDURE IN HEARINGS ON THE RECORD Pre-Hearing Proceedings § 908.46 Discovery. (a) Limits on discovery. Subject to the limitations set out in paragraphs (b), (d), and (e) of this section, any party to...
-
2010-04-01
... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Discovery. 17.23 Section 17.23 Food and Drugs FOOD... HEARINGS § 17.23 Discovery. (a) No later than 60 days prior to the hearing, unless otherwise ordered by the..., depositions, and any forms of discovery, other than those permitted under paragraphs (a) and (e) of this...
-
When fragments link: a bibliometric perspective on the development of fragment-based drug discovery.
Romasanta, Angelo K S; van der Sijde, Peter; Hellsten, Iina; Hubbard, Roderick E; Keseru, Gyorgy M; van Muijlwijk-Koezen, Jacqueline; de Esch, Iwan J P
2018-05-05
Fragment-based drug discovery (FBDD) is a highly interdisciplinary field, rich in ideas integrated from pharmaceutical sciences, chemistry, biology, and physics, among others. To enrich our understanding of the development of the field, we used bibliometric techniques to analyze 3642 publications in FBDD, complementing accounts by key practitioners. Mapping its core papers, we found the transfer of knowledge from academia to industry. Co-authorship analysis showed that university-industry collaboration has grown over time. Moreover, we show how ideas from other scientific disciplines have been integrated into the FBDD paradigm. Keyword analysis showed that the field is organized into four interconnected practices: library design, fragment screening, computational methods, and optimization. This study highlights the importance of interactions among various individuals and institutions from diverse disciplines in newly emerging scientific fields. Copyright © 2018. Published by Elsevier Ltd.
-
Knowledge Discovery and Data Mining in Iran's Climatic Researches
Karimi, Mostafa
2013-04-01
Advances in measurement technology and data collection is the database gets larger. Large databases require powerful tools for analysis data. Iterative process of acquiring knowledge from information obtained from data processing is done in various forms in all scientific fields. However, when the data volume large, and many of the problems the Traditional methods cannot respond. in the recent years, use of databases in various scientific fields, especially atmospheric databases in climatology expanded. in addition, increases in the amount of data generated by the climate models is a challenge for analysis of it for extraction of hidden pattern and knowledge. The approach to this problem has been made in recent years uses the process of knowledge discovery and data mining techniques with the use of the concepts of machine learning, artificial intelligence and expert (professional) systems is overall performance. Data manning is analytically process for manning in massive volume data. The ultimate goal of data mining is access to information and finally knowledge. climatology is a part of science that uses variety and massive volume data. Goal of the climate data manning is Achieve to information from variety and massive atmospheric and non-atmospheric data. in fact, Knowledge Discovery performs these activities in a logical and predetermined and almost automatic process. The goal of this research is study of uses knowledge Discovery and data mining technique in Iranian climate research. For Achieve This goal, study content (descriptive) analysis and classify base method and issue. The result shown that in climatic research of Iran most clustering, k-means and wards applied and in terms of issues precipitation and atmospheric circulation patterns most introduced. Although several studies in geography and climate issues with statistical techniques such as clustering and pattern extraction is done, Due to the nature of statistics and data mining, but cannot say for
-
Discovery and Reuse of Open Datasets: An Exploratory Study
Directory of Open Access Journals (Sweden)
Sara
2016-07-01
Full Text Available Objective: This article analyzes twenty cited or downloaded datasets and the repositories that house them, in order to produce insights that can be used by academic libraries to encourage discovery and reuse of research data in institutional repositories. Methods: Using Thomson Reuters’ Data Citation Index and repository download statistics, we identified twenty cited/downloaded datasets. We documented the characteristics of the cited/downloaded datasets and their corresponding repositories in a self-designed rubric. The rubric includes six major categories: basic information; funding agency and journal information; linking and sharing; factors to encourage reuse; repository characteristics; and data description. Results: Our small-scale study suggests that cited/downloaded datasets generally comply with basic recommendations for facilitating reuse: data are documented well; formatted for use with a variety of software; and shared in established, open access repositories. Three significant factors also appear to contribute to dataset discovery: publishing in discipline-specific repositories; indexing in more than one location on the web; and using persistent identifiers. The cited/downloaded datasets in our analysis came from a few specific disciplines, and tended to be funded by agencies with data publication mandates. Conclusions: The results of this exploratory research provide insights that can inform academic librarians as they work to encourage discovery and reuse of institutional datasets. Our analysis also suggests areas in which academic librarians can target open data advocacy in their communities in order to begin to build open data success stories that will fuel future advocacy efforts.
-
Multi-dimensional discovery of biomarker and phenotype complexes
Directory of Open Access Journals (Sweden)
Huang Kun
2010-10-01
Full Text Available Abstract Background Given the rapid growth of translational research and personalized healthcare paradigms, the ability to relate and reason upon networks of bio-molecular and phenotypic variables at various levels of granularity in order to diagnose, stage and plan treatments for disease states is highly desirable. Numerous techniques exist that can be used to develop networks of co-expressed or otherwise related genes and clinical features. Such techniques can also be used to create formalized knowledge collections based upon the information incumbent to ontologies and domain literature. However, reports of integrative approaches that bridge such networks to create systems-level models of disease or wellness are notably lacking in the contemporary literature. Results In response to the preceding gap in knowledge and practice, we report upon a prototypical series of experiments that utilize multi-modal approaches to network induction. These experiments are intended to elicit meaningful and significant biomarker-phenotype complexes spanning multiple levels of granularity. This work has been performed in the experimental context of a large-scale clinical and basic science data repository maintained by the National Cancer Institute (NCI funded Chronic Lymphocytic Leukemia Research Consortium. Conclusions Our results indicate that it is computationally tractable to link orthogonal networks of genes, clinical features, and conceptual knowledge to create multi-dimensional models of interrelated biomarkers and phenotypes. Further, our results indicate that such systems-level models contain interrelated bio-molecular and clinical markers capable of supporting hypothesis discovery and testing. Based on such findings, we propose a conceptual model intended to inform the cross-linkage of the results of such methods. This model has as its aim the identification of novel and knowledge-anchored biomarker-phenotype complexes.
-
Configurable User Interface Framework for Data Discovery in Cross-Disciplinary and Citizen Science
Rozell, E.; Wang, H.; West, P.; Zednik, S.; Fox, P.
2012-04-01
Use cases for data discovery and analysis vary widely when looking across disciplines and levels of expertise. Domain experts across disciplines may have a thorough understanding of self-describing data formats, such as netCDF, and the software packages that are compatible. However, they may be unfamiliar with specific vocabulary terms used to describe the data parameters or instrument packages in someone else's collection, which are often useful in data discovery. Citizen scientists may struggle with both expert vocabularies and knowledge of existing tools for analyzing and visualizing data. There are some solutions for each problem individually. For expert vocabularies, semantic technologies like the Resource Description Framework (RDF) have been used to map terms from an expert vocabulary to layperson terminology. For data analysis and visualization, tools can be mapped to data products using semantic technologies as well. This presentation discusses a solution to both problems based on the S2S Framework, a configurable user interface (UI) framework for Web services. S2S unifies the two solutions previously described using a data service abstraction ("search services") and a UI abstraction ("widgets"). Using the OWL Web Ontology Language, S2S defines a vocabulary for describing search services and their outputs, and the compatibility of those outputs with UI widgets. By linking search service outputs to widgets, S2S can automatically compose UIs for search and analysis of data, making it easier for citizen scientists to manipulate data. We have also created Linked Data widgets for S2S, which can leverage distributed RDF resources to present alternative views of expert vocabularies. This presentation covers some examples where we have applied these solutions to improve data discovery for both cross-disciplinary and non-expert users.
-
Link-Based Similarity Measures Using Reachability Vectors
Directory of Open Access Journals (Sweden)
Seok-Ho Yoon
2014-01-01
Full Text Available We present a novel approach for computing link-based similarities among objects accurately by utilizing the link information pertaining to the objects involved. We discuss the problems with previous link-based similarity measures and propose a novel approach for computing link based similarities that does not suffer from these problems. In the proposed approach each target object is represented by a vector. Each element of the vector corresponds to all the objects in the given data, and the value of each element denotes the weight for the corresponding object. As for this weight value, we propose to utilize the probability of reaching from the target object to the specific object, computed using the “Random Walk with Restart” strategy. Then, we define the similarity between two objects as the cosine similarity of the two vectors. In this paper, we provide examples to show that our approach does not suffer from the aforementioned problems. We also evaluate the performance of the proposed methods in comparison with existing link-based measures, qualitatively and quantitatively, with respect to two kinds of data sets, scientific papers and Web documents. Our experimental results indicate that the proposed methods significantly outperform the existing measures.
-
On the impact of network dynamics on a discovery protocol for ad-hoc networks
Liu, F.; Heijenk, Geert
A very promising approach to discovering services and context information in ad-hoc networks is based on the use of Attenuated Bloom filters. In this paper we analyze the impact of changes in the connectivity of an ad-hoc network on this approach. We evaluate the performance of the discovery
-
The circumstances of minor planet discovery
International Nuclear Information System (INIS)
Pilcher, F.
1989-01-01
The circumstances of discoveries of minor planets are presented in tabular form. Complete data are given for planets 2125-4044, together with notes pertaining to these planets. Information in the table includes the permanent number; the official name; for planets 330 and forward, the table includes the provisional designation attached to the discovery apparition and the year, month, the day of discovery, and the discovery place
-
Missing Links in Genes to Traits: Toward Teaching for an Integrated Framework of Genetics
Pavlova, Iglika V.; Kreher, Scott A.
2013-01-01
Genetics, one of the most influential fields, underlies all of biology and produces discoveries that are in the news daily. However, many students leave introductory biology and genetics courses lacking a coherent framework of knowledge to use in their daily lives. We identify substantial "missing links" in the teaching of foundational…
-
Alternative Polyadenylation Patterns for Novel Gene Discovery and Classification in Cancer
Directory of Open Access Journals (Sweden)
Oguzhan Begik
2017-07-01
Full Text Available Certain aspects of diagnosis, prognosis, and treatment of cancer patients are still important challenges to be addressed. Therefore, we propose a pipeline to uncover patterns of alternative polyadenylation (APA, a hidden complexity in cancer transcriptomes, to further accelerate efforts to discover novel cancer genes and pathways. Here, we analyzed expression data for 1045 cancer patients and found a significant shift in usage of poly(A signals in common tumor types (breast, colon, lung, prostate, gastric, and ovarian compared to normal tissues. Using machine-learning techniques, we further defined specific subsets of APA events to efficiently classify cancer types. Furthermore, APA patterns were associated with altered protein levels in patients, revealed by antibody-based profiling data, suggesting functional significance. Overall, our study offers a computational approach for use of APA in novel gene discovery and classification in common tumor types, with important implications in basic research, biomarker discovery, and precision medicine approaches.
-
Seko, Atsuto; Hayashi, Hiroyuki; Kashima, Hisashi; Tanaka, Isao
2018-01-01
Chemically relevant compositions (CRCs) and atomic arrangements of inorganic compounds have been collected as inorganic crystal structure databases. Machine learning is a unique approach to search for currently unknown CRCs from vast candidates. Herein we propose matrix- and tensor-based recommender system approaches to predict currently unknown CRCs from database entries of CRCs. Firstly, the performance of the recommender system approaches to discover currently unknown CRCs is examined. A Tucker decomposition recommender system shows the best discovery rate of CRCs as the majority of the top 100 recommended ternary and quaternary compositions correspond to CRCs. Secondly, systematic density functional theory (DFT) calculations are performed to investigate the phase stability of the recommended compositions. The phase stability of the 27 compositions reveals that 23 currently unknown compounds are newly found to be stable. These results indicate that the recommender system has great potential to accelerate the discovery of new compounds.
-
Chen, Xin; Wu, Qiong; Sun, Ruimin; Zhang, Louxin
2012-01-01
The discovery of single-nucleotide polymorphisms (SNPs) has important implications in a variety of genetic studies on human diseases and biological functions. One valuable approach proposed for SNP discovery is based on base-specific cleavage and mass spectrometry. However, it is still very challenging to achieve the full potential of this SNP discovery approach. In this study, we formulate two new combinatorial optimization problems. While both problems are aimed at reconstructing the sample sequence that would attain the minimum number of SNPs, they search over different candidate sequence spaces. The first problem, denoted as SNP - MSP, limits its search to sequences whose in silico predicted mass spectra have all their signals contained in the measured mass spectra. In contrast, the second problem, denoted as SNP - MSQ, limits its search to sequences whose in silico predicted mass spectra instead contain all the signals of the measured mass spectra. We present an exact dynamic programming algorithm for solving the SNP - MSP problem and also show that the SNP - MSQ problem is NP-hard by a reduction from a restricted variation of the 3-partition problem. We believe that an efficient solution to either problem above could offer a seamless integration of information in four complementary base-specific cleavage reactions, thereby improving the capability of the underlying biotechnology for sensitive and accurate SNP discovery.
-
Deep data: discovery and visualization Application to hyperspectral ALMA imagery
Merényi, Erzsébet; Taylor, Joshua; Isella, Andrea
2017-06-01
Leading-edge telescopes such as the Atacama Large Millimeter and sub-millimeter Array (ALMA), and near-future ones, are capable of imaging the same sky area at hundreds-to-thousands of frequencies with both high spectral and spatial resolution. This provides unprecedented opportunities for discovery about the spatial, kinematical and compositional structure of sources such as molecular clouds or protoplanetary disks, and more. However, in addition to enormous volume, the data also exhibit unprecedented complexity, mandating new approaches for extracting and summarizing relevant information. Traditional techniques such as examining images at selected frequencies become intractable while tools that integrate data across frequencies or pixels (like moment maps) can no longer fully exploit and visualize the rich information. We present a neural map-based machine learning approach that can handle all spectral channels simultaneously, utilizing the full depth of these data for discovery and visualization of spectrally homogeneous spatial regions (spectral clusters) that characterize distinct kinematic behaviors. We demonstrate the effectiveness on an ALMA image cube of the protoplanetary disk HD142527. The tools we collectively name ``NeuroScope'' are efficient for ``Big Data'' due to intelligent data summarization that results in significant sparsity and noise reduction. We also demonstrate a new approach to automate our clustering for fast distillation of large data cubes.
-
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.
-
Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method
Directory of Open Access Journals (Sweden)
Irene Niks
2018-02-01
Full Text Available Effective interventions to prevent work stress and to improve health, well-being, and performance of employees are of the utmost importance. This quasi-experimental intervention study presents a specific method for diagnosis of psychosocial risk factors at work and subsequent development and implementation of tailored work stress interventions, the so-called DISCovery method. This method aims at improving employee health, well-being, and performance by optimizing the balance between job demands, job resources, and recovery from work. The aim of the study is to quantitatively assess the effectiveness of the DISCovery method in hospital care. Specifically, we used a three-wave longitudinal, quasi-experimental multiple-case study approach with intervention and comparison groups in health care work. Positive changes were found for members of the intervention groups, relative to members of the corresponding comparison groups, with respect to targeted work-related characteristics and targeted health, well-being, and performance outcomes. Overall, results lend support for the effectiveness of the DISCovery method in hospital care.
-
Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method.
Niks, Irene; de Jonge, Jan; Gevers, Josette; Houtman, Irene
2018-02-13
Effective interventions to prevent work stress and to improve health, well-being, and performance of employees are of the utmost importance. This quasi-experimental intervention study presents a specific method for diagnosis of psychosocial risk factors at work and subsequent development and implementation of tailored work stress interventions, the so-called DISCovery method. This method aims at improving employee health, well-being, and performance by optimizing the balance between job demands, job resources, and recovery from work. The aim of the study is to quantitatively assess the effectiveness of the DISCovery method in hospital care. Specifically, we used a three-wave longitudinal, quasi-experimental multiple-case study approach with intervention and comparison groups in health care work. Positive changes were found for members of the intervention groups, relative to members of the corresponding comparison groups, with respect to targeted work-related characteristics and targeted health, well-being, and performance outcomes. Overall, results lend support for the effectiveness of the DISCovery method in hospital care.
-
Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method
Niks, Irene; Gevers, Josette
2018-01-01
Effective interventions to prevent work stress and to improve health, well-being, and performance of employees are of the utmost importance. This quasi-experimental intervention study presents a specific method for diagnosis of psychosocial risk factors at work and subsequent development and implementation of tailored work stress interventions, the so-called DISCovery method. This method aims at improving employee health, well-being, and performance by optimizing the balance between job demands, job resources, and recovery from work. The aim of the study is to quantitatively assess the effectiveness of the DISCovery method in hospital care. Specifically, we used a three-wave longitudinal, quasi-experimental multiple-case study approach with intervention and comparison groups in health care work. Positive changes were found for members of the intervention groups, relative to members of the corresponding comparison groups, with respect to targeted work-related characteristics and targeted health, well-being, and performance outcomes. Overall, results lend support for the effectiveness of the DISCovery method in hospital care. PMID:29438350
-
mHealth Visual Discovery Dashboard.
Fang, Dezhi; Hohman, Fred; Polack, Peter; Sarker, Hillol; Kahng, Minsuk; Sharmin, Moushumi; al'Absi, Mustafa; Chau, Duen Horng
2017-09-01
We present Discovery Dashboard, a visual analytics system for exploring large volumes of time series data from mobile medical field studies. Discovery Dashboard offers interactive exploration tools and a data mining motif discovery algorithm to help researchers formulate hypotheses, discover trends and patterns, and ultimately gain a deeper understanding of their data. Discovery Dashboard emphasizes user freedom and flexibility during the data exploration process and enables researchers to do things previously challenging or impossible to do - in the web-browser and in real time. We demonstrate our system visualizing data from a mobile sensor study conducted at the University of Minnesota that included 52 participants who were trying to quit smoking.
-
Hsu, L.; Lehnert, K. A.; Carbotte, S. M.; Arko, R. A.; Ferrini, V.; O'hara, S. H.; Walker, J. D.
2012-12-01
The Integrated Earth Data Applications (IEDA) facility maintains multiple data systems with a wide range of solid earth data types from the marine, terrestrial, and polar environments. Examples of the different data types include syntheses of ultra-high resolution seafloor bathymetry collected on large collaborative cruises and analytical geochemistry measurements collected by single investigators in small, unique projects. These different data types have historically been channeled into separate, discipline-specific databases with search and retrieval tailored for the specific data type. However, a current major goal is to integrate data from different systems to allow interdisciplinary data discovery and scientific analysis. To increase discovery and access across these heterogeneous systems, IEDA employs several unique IDs, including sample IDs (International Geo Sample Number, IGSN), person IDs (GeoPass ID), funding award IDs (NSF Award Number), cruise IDs (from the Marine Geoscience Data System Expedition Metadata Catalog), dataset IDs (DOIs), and publication IDs (DOIs). These IDs allow linking of a sample registry (System for Earth SAmple Registration), data libraries and repositories (e.g. Geochemical Research Library, Marine Geoscience Data System), integrated synthesis databases (e.g. EarthChem Portal, PetDB), and investigator services (IEDA Data Compliance Tool). The linked systems allow efficient discovery of related data across different levels of granularity. In addition, IEDA data systems maintain links with several external data systems, including digital journal publishers. Links have been established between the EarthChem Portal and ScienceDirect through publication DOIs, returning sample-level objects and geochemical analyses for a particular publication. Linking IEDA-hosted data to digital publications with IGSNs at the sample level and with IEDA-allocated dataset DOIs are under development. As an example, an individual investigator could sign up
-
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
-
The development of high-content screening (HCS) technology and its importance to drug discovery.
Fraietta, Ivan; Gasparri, Fabio
2016-01-01
High-content screening (HCS) was introduced about twenty years ago as a promising analytical approach to facilitate some critical aspects of drug discovery. Its application has spread progressively within the pharmaceutical industry and academia to the point that it today represents a fundamental tool in supporting drug discovery and development. Here, the authors review some of significant progress in the HCS field in terms of biological models and assay readouts. They highlight the importance of high-content screening in drug discovery, as testified by its numerous applications in a variety of therapeutic areas: oncology, infective diseases, cardiovascular and neurodegenerative diseases. They also dissect the role of HCS technology in different phases of the drug discovery pipeline: target identification, primary compound screening, secondary assays, mechanism of action studies and in vitro toxicology. Recent advances in cellular assay technologies, such as the introduction of three-dimensional (3D) cultures, induced pluripotent stem cells (iPSCs) and genome editing technologies (e.g., CRISPR/Cas9), have tremendously expanded the potential of high-content assays to contribute to the drug discovery process. Increasingly predictive cellular models and readouts, together with the development of more sophisticated and affordable HCS readers, will further consolidate the role of HCS technology in drug discovery.
-
Integration of Lead Discovery Tactics and the Evolution of the Lead Discovery Toolbox.
Leveridge, Melanie; Chung, Chun-Wa; Gross, Jeffrey W; Phelps, Christopher B; Green, Darren
2018-06-01
There has been much debate around the success rates of various screening strategies to identify starting points for drug discovery. Although high-throughput target-based and phenotypic screening has been the focus of this debate, techniques such as fragment screening, virtual screening, and DNA-encoded library screening are also increasingly reported as a source of new chemical equity. Here, we provide examples in which integration of more than one screening approach has improved the campaign outcome and discuss how strengths and weaknesses of various methods can be used to build a complementary toolbox of approaches, giving researchers the greatest probability of successfully identifying leads. Among others, we highlight case studies for receptor-interacting serine/threonine-protein kinase 1 and the bromo- and extra-terminal domain family of bromodomains. In each example, the unique insight or chemistries individual approaches provided are described, emphasizing the synergy of information obtained from the various tactics employed and the particular question each tactic was employed to answer. We conclude with a short prospective discussing how screening strategies are evolving, what this screening toolbox might look like in the future, how to maximize success through integration of multiple tactics, and scenarios that drive selection of one combination of tactics over another.
-
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.
-
Open Drug Discovery Toolkit (ODDT): a new open-source player in the drug discovery field.
Wójcikowski, Maciej; Zielenkiewicz, Piotr; Siedlecki, Pawel
2015-01-01
There has been huge progress in the open cheminformatics field in both methods and software development. Unfortunately, there has been little effort to unite those methods and software into one package. We here describe the Open Drug Discovery Toolkit (ODDT), which aims to fulfill the need for comprehensive and open source drug discovery software. The Open Drug Discovery Toolkit was developed as a free and open source tool for both computer aided drug discovery (CADD) developers and researchers. ODDT reimplements many state-of-the-art methods, such as machine learning scoring functions (RF-Score and NNScore) and wraps other external software to ease the process of developing CADD pipelines. ODDT is an out-of-the-box solution designed to be easily customizable and extensible. Therefore, users are strongly encouraged to extend it and develop new methods. We here present three use cases for ODDT in common tasks in computer-aided drug discovery. Open Drug Discovery Toolkit is released on a permissive 3-clause BSD license for both academic and industrial use. ODDT's source code, additional examples and documentation are available on GitHub (https://github.com/oddt/oddt).
-
a Task-Driven Disaster Data Link Approach
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.
-
The in silico drug discovery toolbox: applications in lead discovery and optimization.
Bruno, Agostino; Costantino, Gabriele; Sartori, Luca; Radi, Marco
2017-11-06
Discovery and development of a new drug is a long lasting and expensive journey that takes around 15 years from starting idea to approval and marketing of new medication. Despite the R&D expenditures have been constantly increasing in the last few years, number of new drugs introduced into market has been steadily declining. This is mainly due to preclinical and clinical safety issues, which still represent about 40% of drug discontinuation. From this point of view, it is clear that if we want to increase drug-discovery success rate and reduce costs associated with development of a new drug, a comprehensive evaluation/prediction of potential safety issues should be conducted as soon as possible during early drug discovery phase. In the present review, we will analyse the early steps of drug-discovery pipeline, describing the sequence of steps from disease selection to lead optimization and focusing on the most common in silico tools used to assess attrition risks and build a mitigation plan. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
-
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...
-
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
-
Biomarker Gene Signature Discovery Integrating Network Knowledge
Directory of Open Access Journals (Sweden)
Holger Fröhlich
2012-02-01
Full Text Available Discovery of prognostic and diagnostic biomarker gene signatures for diseases, such as cancer, is seen as a major step towards a better personalized medicine. During the last decade various methods, mainly coming from the machine learning or statistical domain, have been proposed for that purpose. However, one important obstacle for making gene signatures a standard tool in clinical diagnosis is the typical low reproducibility of these signatures combined with the difficulty to achieve a clear biological interpretation. For that purpose in the last years there has been a growing interest in approaches that try to integrate information from molecular interaction networks. Here we review the current state of research in this field by giving an overview about so-far proposed approaches.
-
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.
-
In silico tools used for compound selection during target-based drug discovery and development.
Caldwell, Gary W
2015-01-01
The target-based drug discovery process, including target selection, screening, hit-to-lead (H2L) and lead optimization stage gates, is the most common approach used in drug development. The full integration of in vitro and/or in vivo data with in silico tools across the entire process would be beneficial to R&D productivity by developing effective selection criteria and drug-design optimization strategies. This review focuses on understanding the impact and extent in the past 5 years of in silico tools on the various stage gates of the target-based drug discovery approach. There are a large number of in silico tools available for establishing selection criteria and drug-design optimization strategies in the target-based approach. However, the inconsistent use of in vitro and/or in vivo data integrated with predictive in silico multiparameter models throughout the process is contributing to R&D productivity issues. In particular, the lack of reliable in silico tools at the H2L stage gate is contributing to the suboptimal selection of viable lead compounds. It is suggested that further development of in silico multiparameter models and organizing biologists, medicinal and computational chemists into one team with a single accountable objective to expand the utilization of in silico tools in all phases of drug discovery would improve R&D productivity.
-
Discovery Mondays - “Relativity Theory... strange! Did you say strange?”
2005-01-01
We all know that famous equation E=mc2, but do you know its true significance? Relativity theory: what is the meaning of this strange concept which plunged the physics world into turmoil 100 years ago? What effects can be observed today? Did you know that the GPS system would not work if relativity was not taken into account? The next Discovery Monday will take you on a journey into a strange world. You will be able to witness for yourselves the consequences of Einstein's theories. How, for example, can relativity theory be tested by eclipses? What consequences does it have for the accelerators at CERN? How can it be used to measure the mass of enormous black holes? And finally, how is it linked to the puzzle surrounding the missing mass of the Universe? As part of the World Year of Physics, the next Discovery Monday will be dedicated to one of the theories that Einstein published in 1905, his “annus mirabilis”. Join us at the Microcosm (Reception Building 33, Meyrin site), on Monday 5th September ...
-
Discovery Mondays - “Relativity Theory... strange! Did you say strange?”
2005-01-01
We all know that famous equation E=mc2, but do you know its true significance? Relativity theory: what is the meaning of this strange concept which plunged the physics world into turmoil 100 years ago? What effects can be observed today? Did you know that the GPS system would not work if relativity was not taken into account? The next Discovery Monday will take you on a journey into a strange world. You will be able to witness for yourselves the consequences of Einstein's theories. How, for example, can relativity theory be tested by eclipses? What consequences does it have for the accelerators at CERN? How can it be used to measure the mass of enormous black holes? And finally, how is it linked to the puzzle surrounding the missing mass of the Universe? As part of the World Year of Physics, the next Discovery Monday will be dedicated to one of the theories that Einstein published in 1905, his “annus mirabilis”. Join us at the Microcosm (Reception Building 33, Meyrin site), on Monday 5th Septemb...
-
Simulated drug discovery process to conduct a synoptic assessment of pharmacy students.
Richardson, Alan; Curtis, Anthony D M; Moss, Gary P; Pearson, Russell J; White, Simon; Rutten, Frank J M; Perumal, Dhaya; Maddock, Katie
2014-03-12
OBJECTIVE. To implement and assess a task-based learning exercise that prompts pharmacy students to integrate their understanding of different disciplines. DESIGN. Master of pharmacy (MPharm degree) students were provided with simulated information from several preclinical science and from clinical trials and asked to synthesize this into a marketing authorization application for a new drug. Students made a link to pharmacy practice by creating an advice leaflet for pharmacists. ASSESSMENT. Students' ability to integrate information from different disciplines was evaluated by oral examination. In 2 successive academic years, 96% and 82% of students demonstrated an integrated understanding of their proposed new drug. Students indicated in a survey that their understanding of the links between different subjects improved. CONCLUSION. Simulated drug discovery provides a learning environment that emphasizes the connectivity of the preclinical sciences with each other and the practice of pharmacy.
-
Directory of Open Access Journals (Sweden)
Konstantin Okonechnikov
Full Text Available Analysis of fusion transcripts has become increasingly important due to their link with cancer development. Since high-throughput sequencing approaches survey fusion events exhaustively, several computational methods for the detection of gene fusions from RNA-seq data have been developed. This kind of analysis, however, is complicated by native trans-splicing events, the splicing-induced complexity of the transcriptome and biases and artefacts introduced in experiments and data analysis. There are a number of tools available for the detection of fusions from RNA-seq data; however, certain differences in specificity and sensitivity between commonly used approaches have been found. The ability to detect gene fusions of different types, including isoform fusions and fusions involving non-coding regions, has not been thoroughly studied yet. Here, we propose a novel computational toolkit called InFusion for fusion gene detection from RNA-seq data. InFusion introduces several unique features, such as discovery of fusions involving intergenic regions, and detection of anti-sense transcription in chimeric RNAs based on strand-specificity. Our approach demonstrates superior detection accuracy on simulated data and several public RNA-seq datasets. This improved performance was also evident when evaluating data from RNA deep-sequencing of two well-established prostate cancer cell lines. InFusion identified 26 novel fusion events that were validated in vitro, including alternatively spliced gene fusion isoforms and chimeric transcripts that include intergenic regions. The toolkit is freely available to download from http:/bitbucket.org/kokonech/infusion.
-
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
-
Summary of the BioLINK SIG 2013 meeting at ISMB/ECCB 2013.
Verspoor, Karin; Shatkay, Hagit; Hirschman, Lynette; Blaschke, Christian; Valencia, Alfonso
2015-01-15
The ISMB Special Interest Group on Linking Literature, Information and Knowledge for Biology (BioLINK) organized a one-day workshop at ISMB/ECCB 2013 in Berlin, Germany. The theme of the workshop was 'Roles for text mining in biomedical knowledge discovery and translational medicine'. This summary reviews the outcomes of the workshop. Meeting themes included concept annotation methods and applications, extraction of biological relationships and the use of text-mined data for biological data analysis. All articles are available at http://biolinksig.org/proceedings-online/. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
-
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...
-
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.
-
The discovery of radioactivity: the centenary
International Nuclear Information System (INIS)
Patil, S.K.
1995-01-01
In the last decade of the nineteenth century, a number of fundamental discoveries of outstanding importance were made unexpectedly which marked the beginning of a new era in physics. A cascade of spectacular discoveries began with the announcement of the discovery of x-rays by Roentgen followed by the discoveries, in quick succession, of radioactivity by Becquerel, of Zeeman effect, of electron by J.J. Thomson, and of polonium and radium by the Curies. Both x-rays and radioactivity have wide applications in scientific, medical and industrial fields and have made outstanding contribution to the advancement of human knowledge and welfare. Radioactivity is well known and no other discovery in the field of physics or chemistry has had a more profound effect on our fundamental knowledge of nature. Present article, on the occasion of the centenary of the discovery of radioactivity, makes an attempt to describe some glimpses of the history of radioactivity. (author). 59 refs
-
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.)
-
Established and Emerging Trends in Computational Drug Discovery in the Structural Genomics Era
DEFF Research Database (Denmark)
Taboureau, Olivier; Baell, Jonathan B.; Fernández-Recio, Juan
2012-01-01
Bioinformatics and chemoinformatics approaches contribute to hit discovery, hit-to-lead optimization, safety profiling, and target identification and enhance our overall understanding of the health and disease states. A vast repertoire of computational methods has been reported and increasingly...
-
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
-
Clinical impact of recent genetic discoveries in osteoporosis
Directory of Open Access Journals (Sweden)
Mitchell BD
2013-10-01
Full Text Available Braxton D Mitchell, Elizabeth A StreetenDepartment of Medicine and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, and Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, MD, USAAbstract: Osteoporotic fracture carries an enormous public health burden in terms of mortality and morbidity. Current approaches to identify individuals at high risk for fracture are based on assessment of bone mineral density and presence of other osteoporosis risk factors. Bone mineral density and susceptibility to osteoporotic fractures are highly heritable, and over 60 loci have been robustly associated with one or both traits through genome-wide association studies carried out over the past 7 years. In this review, we discuss opportunities and challenges for incorporating these genetic discoveries into strategies to prevent osteoporotic fracture and translating new insights obtained from these discoveries into development of new therapeutic targets.Keywords: bone mineral density, genome-wide association studies, osteoporosis, prediction, fracture, genetics
-
Scientific Knowledge Discovery in Complex Semantic Networks of Geophysical Systems
Fox, P.
2012-04-01
The vast majority of explorations of the Earth's systems are limited in their ability to effectively explore the most important (often most difficult) problems because they are forced to interconnect at the data-element, or syntactic, level rather than at a higher scientific, or semantic, level. Recent successes in the application of complex network theory and algorithms to climate data, raise expectations that more general graph-based approaches offer the opportunity for new discoveries. In the past ~ 5 years in the natural sciences there has substantial progress in providing both specialists and non-specialists the ability to describe in machine readable form, geophysical quantities and relations among them in meaningful and natural ways, effectively breaking the prior syntax barrier. The corresponding open-world semantics and reasoning provide higher-level interconnections. That is, semantics provided around the data structures, using semantically-equipped tools, and semantically aware interfaces between science application components allowing for discovery at the knowledge level. More recently, formal semantic approaches to continuous and aggregate physical processes are beginning to show promise and are soon likely to be ready to apply to geoscientific systems. To illustrate these opportunities, this presentation presents two application examples featuring domain vocabulary (ontology) and property relations (named and typed edges in the graphs). First, a climate knowledge discovery pilot encoding and exploration of CMIP5 catalog information with the eventual goal to encode and explore CMIP5 data. Second, a multi-stakeholder knowledge network for integrated assessments in marine ecosystems, where the data is highly inter-disciplinary.
-
Dewey linked data: Making connections with old friends and new acquaintances
Directory of Open Access Journals (Sweden)
Joan S. Mitchell
2013-01-01
Full Text Available This paper explores the history, uses cases, and future plans associated with availability of the Dewey Decimal Classification (DDC system as linked data. Parts of DDC system have been available as linked data since 2009. Initial efforts included the DDC Summaries in eleven languages exposed as linked data in dewey.info. In 2010, the content of dewey.info was further extended by the addition of assignable numbers and captions from the Abridged Edition 14 data files in English, Italian, and Vietnamese. During 2012, we will add assignable numbers and captions from the latest full edition database, DDC 23. In addition to the “old friends” of different Dewey language versions, institutions such as the British Library and Deutsche Nationalbibliothek have made use of Dewey linked data in bibliographic records and authority files, and AGROVOC has linked to our data at a general level. We expect to extend our linked data network shortly to “new acquaintances” such as GeoNames, ISO 639-3 language codes, and Mathematics Subject Classification. In particular, the paper examines the linking process to GeoNames as an example of cross-domain vocabulary alignment. In addition to linking plans, the paper reports on use cases that facilitate machine-assisted categorization and support discovery in the semantic web environment.
-
'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”.
-
Computational methods in drug discovery
Sumudu P. Leelananda; Steffen Lindert
2016-01-01
The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery project...
-
Choosing Discovery: A Literature Review on the Selection and Evaluation of Discovery Layers
Moore, Kate B.; Greene, Courtney
2012-01-01
Within the next few years, traditional online public access catalogs will be replaced by more robust and interconnected discovery layers that can serve as primary public interfaces to simultaneously search many separate collections of resources. Librarians have envisioned this type of discovery tool since the 1980s, and research shows that…
-
Investigations into Library Web-Scale Discovery Services
Directory of Open Access Journals (Sweden)
Jason Vaughan
2008-03-01
Full Text Available Web-scale discovery services for libraries provide deep discovery to a library’s local and licensed content, and represent an evolution, perhaps a revolution, for end user information discovery as pertains to library collections. This article frames the topic of web-scale discovery, and begins by illuminating web-scale discovery from an academic library’s perspective – that is, the internal perspective seeking widespread staff participation in the discovery conversation. This included the creation of a discovery task force, a group which educated library staff, conducted internal staff surveys, and gathered observations from early adopters. The article next addresses the substantial research conducted with library vendors which have developed these services. Such work included drafting of multiple comprehensive question lists distributed to the vendors, onsite vendor visits, and continual tracking of service enhancements. Together, feedback gained from library staff, insights arrived at by the Discovery Task Force, and information gathered from vendors collectively informed the recommendation of a service for the UNLV Libraries.
-
The Europa Ocean Discovery mission
Energy Technology Data Exchange (ETDEWEB)
Edwards, B.C. [Los Alamos National Lab., NM (United States); Chyba, C.F. [Univ. of Arizona, Tucson, AZ (United States); Abshire, J.B. [National Aeronautics and Space Administration, Greenbelt, MD (United States). Goddard Space Flight Center] [and others
1997-06-01
Since it was first proposed that tidal heating of Europa by Jupiter might lead to liquid water oceans below Europa`s ice cover, there has been speculation over the possible exobiological implications of such an ocean. Liquid water is the essential ingredient for life as it is known, and the existence of a second water ocean in the Solar System would be of paramount importance for seeking the origin and existence of life beyond Earth. The authors present here a Discovery-class mission concept (Europa Ocean Discovery) to determine the existence of a liquid water ocean on Europa and to characterize Europa`s surface structure. The technical goal of the Europa Ocean Discovery mission is to study Europa with an orbiting spacecraft. This goal is challenging but entirely feasible within the Discovery envelope. There are four key challenges: entering Europan orbit, generating power, surviving long enough in the radiation environment to return valuable science, and complete the mission within the Discovery program`s launch vehicle and budget constraints. The authors will present here a viable mission that meets these challenges.
-
Fragment-Based Drug Discovery in the Bromodomain and Extra-Terminal Domain Family.
Radwan, Mostafa; Serya, Rabah
2017-08-01
Bromodomain and extra-terminal domain (BET) inhibition has emerged recently as a potential therapeutic target for the treatment of many human disorders such as atherosclerosis, inflammatory disorders, chronic obstructive pulmonary disease (COPD), some viral infections, and cancer. Since the discovery of the two potent inhibitors, I-BET762 and JQ1, different research groups have used different techniques to develop novel potent and selective inhibitors. In this review, we will be concerned with the trials that used fragment-based drug discovery (FBDD) approaches to discover or optimize BET inhibitors, also showing fragments that can be further optimized in future projects to reach novel potent BET inhibitors. © 2017 Deutsche Pharmazeutische Gesellschaft.
-
The impact of data integrity on decision making in early lead discovery
Beck, Bernd; Seeliger, Daniel; Kriegl, Jan M.
2015-09-01
Data driven decision making is a key element of today's pharmaceutical research, including early drug discovery. It comprises questions like which target to pursue, which chemical series to pursue, which compound to make next, or which compound to select for advanced profiling and promotion to pre-clinical development. In the following paper we will exemplify how data integrity, i.e. the context data is generated in and auxiliary information that is provided for individual result records, can influence decision making in early lead discovery programs. In addition we will describe some approaches which we pursue at Boehringer Ingelheim to reduce the risk for getting misguided.
-
The EEE-05 Challenge: A New Web Service Discovery and Composition Competition
Blake, M. Brian; Tsui, Kwok Ching; Wombacher, Andreas
With growing acceptance of service-oriented computing, an emerging area of research is the investigation of technologies that will enable the discovery and composition of web services. Using the same approach as the popular Trading Agent Competitions (TAC), the EEE-05 Web Services Challenge is the
-
29 CFR 18.13 - Discovery methods.
2010-07-01
... 29 Labor 1 2010-07-01 2010-07-01 true Discovery methods. 18.13 Section 18.13 Labor Office of the... ADMINISTRATIVE LAW JUDGES General § 18.13 Discovery methods. Parties may obtain discovery by one or more of the following methods: Depositions upon oral examination or written questions; written interrogatories...
-
Anticancer drug discovery and pharmaceutical chemistry: a history.
Braña, Miguel F; Sánchez-Migallón, Ana
2006-10-01
There are several procedures for the chemical discovery and design of new drugs from the point of view of the pharmaceutical or medicinal chemistry. They range from classical methods to the very new ones, such as molecular modeling or high throughput screening. In this review, we will consider some historical approaches based on the screening of natural products, the chances for luck, the systematic screening of new chemical entities and serendipity. Another group comprises rational design, as in the case of metabolic pathways, conformation versus configuration and, finally, a brief description on available new targets to be carried out. In each approach, the structure of some examples of clinical interest will be shown.
-
Discovery of the neutron (to the fiftieth anniversary of neutron discovery)
International Nuclear Information System (INIS)
Pasechnik, M.V.
1984-01-01
Development of neutron physics in the USSR for the recent 50 years from the moment of neutron discovery is considered. History of neutron discovery is presented in brief. Neutron properties and fundamental problems of physics: electric dipole neutron moment, neutron β-decay, neutron interaction with nuclei and potential of nucleon interaction not conserving spatial parity are discussed. Main aspects of neutron physics application in power engineering, nuclear technology and other branches of science and technique are set forth
-
Directory of Open Access Journals (Sweden)
Ryu Miura
2013-06-01
Full Text Available An essential application of wireless sensor networks is to successfully respond to user queries. Query packet losses occur in the query dissemination due to wireless communication problems such as interference, multipath fading, packet collisions, etc. The losses of query messages at sensor nodes result in the failure of sensor nodes reporting the requested data. Hence, the reliable and successful dissemination of query messages to sensor nodes is a non-trivial problem. The target of this paper is to enable highly successful query delivery to sensor nodes by localized and energy-efficient discovery, and recovery of query losses. We adopt local and collective cooperation among sensor nodes to increase the success rate of distributed discoveries and recoveries. To enable the scalability in the operations of discoveries and recoveries, we employ a distributed name resolution mechanism at each sensor node to allow sensor nodes to self-detect the correlated queries and query losses, and then efficiently locally respond to the query losses. We prove that the collective discovery of query losses has a high impact on the success of query dissemination and reveal that scalability can be achieved by using the proposed approach. We further study the novel features of the cooperation and competition in the collective recovery at PHY and MAC layers, and show that the appropriate number of detectors can achieve optimal successful recovery rate. We evaluate the proposed approach with both mathematical analyses and computer simulations. The proposed approach enables a high rate of successful delivery of query messages and it results in short route lengths to recover from query losses. The proposed approach is scalable and operates in a fully distributed manner.